PMID- 29784870 TI - Rethinking assumptions about delivery of healthcare: implications for universal health coverage. PMID- 29784871 TI - Effect of maternal hypothyroidism during pregnancy on insulin resistance, lipid accumulation, and mitochondrial dysfunction in skeletal muscle of fetal rats. AB - The present study aimed to investigate the effect of maternal hypothyroidism during pregnancy on thyroid function of the fetal rat. Female Sprague-Dawley rats were randomized into two groups. Propylthiouracil (PTU) group received PTU in drinking water for 6 weeks (n=90), normal group received normal drinking water (n=50). The pregnant rats were obtained and had a cesarean-section to get at gestational ages of 8.5, 13, and 21 days, following blood samples and skeletal muscle were obtained from fetal rats. Levels of thyroid hormone, insulin, mitochondrial protein, and adipokines were detected using ELISA. Western blotting was performed to analyze mitochondria and insulin signal transduction-related protein in fetal rat skeletal muscle. Immunostaining of Periodic Acid-Schiff (PAS) and Oil Red O was used to observe the accumulation of muscle glycogen and lipid in the fetal rat. The results showed that the levels of thyroid hormone, insulin, insulin signal transduction-related protein, mitochondrial, and adipokines increased with the fetus developed, but had no statistical differences in the PTU group compared with the normal group. In conclusion, pregnant rats with hypothyroidism had no influence on insulin resistance (IR), lipid accumulation, and mitochondrial dysfunction in skeletal muscle of the fetal rats. PMID- 29784872 TI - SIRT1 inhibits rheumatoid arthritis fibroblast-like synoviocyte aggressiveness and inflammatory response via suppressing NF-kappaB pathway. AB - Rheumatoid arthritis (RA) is an autoimmune disease of the joints characterized by synovial hyperplasia and chronic inflammation. Fibroblast-like synoviocytes (FLS) play a central role in RA initiation, progression, and perpetuation. Prior studies showed that sirtuin 1 (SIRT1), a deacetylase participating in a broad range of transcriptional and metabolic regulations, may impact cell proliferation and inflammatory responses. However, the role of SIRT1 in RA-FLS was unclear. Here, we explored the effects of SIRT1 on the aggressiveness and inflammatory responses of cultured RA-FLS. SIRT1 expression was significantly lower in synovial tissues and FLS from RA patients than from healthy controls. Overexpression of SIRT1 significantly inhibited RA-FLS proliferation, migration, and invasion. SIRT1 overexpression also significantly increased RA-FLS apoptosis and caspase-3 and -8 activity. Focusing on inflammatory phenotypes, we found SIRT1 significantly reduced RA-FLS secretion of TNF-alpha, IL-6, IL-8, and IL 1beta. Mechanistic studies further revealed SIRT1 suppressed NF-kappaB pathway by reducing p65 protein expression, phosphorylation, and acetylation in RA-FLS. Our results suggest SIRT1 is a key regulator in RA pathogenesis by suppressing aggressive phenotypes and inflammatory response of FLS. Enhancing SIRT1 expression or function in FLS could be therapeutic beneficial for RA by inhibiting synovial hyperplasia and inflammation. PMID- 29784873 TI - Chemokine (C-X-C motif) ligand 1 is associated with tumor progression and poor prognosis in patients with colorectal cancer. AB - Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients' samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment. PMID- 29784874 TI - Select alpha-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model. AB - Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K+ inward rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific alpha arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 alpha-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorogen activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two alpha-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the alpha-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate alpha-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast. PMID- 29784875 TI - A human-specific, truncated alpha7 nicotinic receptor subunit assembles with full length alpha7 and forms functional receptors with different stoichiometries. AB - The cholinergic alpha7 nicotinic receptor gene, CHRNA7, encodes a subunit that forms the homopentameric alpha7 receptor, involved in learning and memory. In humans, exons 5-10 in CHRNA7 are duplicated and fused to the FAM7A genetic element, giving rise to the hybrid gene CHRFAM7A Its product, dupalpha7, is a truncated subunit lacking part of the N-terminal extracellular ligand-binding domain and is associated with neurological disorders, including schizophrenia, and immunomodulation. We combined dupalpha7 expression on mammalian cells with patch clamp recordings to understand its functional role. Transfected cells expressed dupalpha7 protein, but they exhibited neither surface binding of the alpha7 antagonist alpha-bungarotoxin nor responses to acetylcholine (ACh) or to an allosteric agonist that binds to the conserved transmembrane region. To determine whether dupalpha7 assembles with alpha7, we generated receptors comprising alpha7 and dupalpha7 subunits, one of which was tagged with conductance substitutions that report subunit stoichiometry and monitored ACh elicited channel openings in the presence of a positive allosteric alpha7 modulator. We found that alpha7 and dupalpha7 subunits co-assemble into functional heteromeric receptors, which require at least two alpha7 subunits for channel opening, and that dupalpha7's presence in the pentameric arrangement does not affect the duration of the potentiated events compared with that of alpha7. Using an alpha7 subunit mutant, we found that activation of (alpha7)2(dupalpha7)3 receptors occurs through ACh binding at the alpha7/alpha7 interfacial binding site. Our study contributes to the understanding of the modulation of alpha7 function by the human specific, duplicated subunit, associated with human disorders. PMID- 29784876 TI - CHCA-1 is a copper-regulated CTR1 homolog required for normal development, copper accumulation, and copper-sensing behavior in Caenorhabditis elegans. AB - Copper plays key roles in catalytic and regulatory biochemical reactions essential for normal growth, development, and health. Dietary copper deficiencies or mutations in copper homeostasis genes can lead to abnormal musculoskeletal development, cognitive disorders, and poor growth. In yeast and mammals, copper is acquired through the activities of the CTR1 family of high-affinity copper transporters. However, the mechanisms of systemic responses to dietary or tissue specific copper deficiency remain unclear. Here, taking advantage of the animal model Caenorhabditis elegans for studying whole-body copper homeostasis, we investigated the role of a C. elegans CTR1 homolog, CHCA-1, in copper acquisition and in worm growth, development, and behavior. Using sequence homology searches, we identified 10 potential orthologs to mammalian CTR1 Among these genes, we found that chca-1, which is transcriptionally up-regulated in the intestine and hypodermis of C. elegans during copper deficiency, is required for normal growth, reproduction, and maintenance of systemic copper balance under copper deprivation. The intestinal copper transporter CUA-1 normally traffics to endosomes to sequester excess copper, and we found here that loss of chca-1 caused CUA-1 to mislocalize to the basolateral membrane under copper overload conditions. Moreover, animals lacking chca-1 exhibited significantly reduced copper avoidance behavior in response to toxic copper conditions compared with WT worms. These results establish that CHCA-1-mediated copper acquisition in C. elegans is crucial for normal growth, development, and copper-sensing behavior. PMID- 29784877 TI - Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities. AB - 3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is an iron-dependent protein that activates O2 and inserts both oxygen atoms into 3-hydroxyanthranilate (3-HAA). An intriguing question is how HAO can rapidly bind O2, even though local O2 concentrations and diffusion rates are relatively low. Here, a close inspection of the HAO structures revealed that substrate- and inhibitor-bound structures exhibit a closed conformation with three hydrophobic loop regions moving toward the catalytic iron center, whereas the ligand-free structure is open. We hypothesized that these loop movements enhance O2 binding to the binary complex of HAO and 3-HAA. We found that the carboxyl end of 3-HAA triggers changes in two loop regions and that the third loop movement appears to be driven by an H-bond interaction between Asn27 and Ile142 Mutational analyses revealed that N27A, I142A, and I142P variants cannot form a closed conformation, and steady-state kinetic assays indicated that these variants have a substantially higher Km for O2 than WT HAO. This observation suggested enhanced hydrophobicity at the iron center resulting from the concerted loop movements after the binding of the primary substrate, which is hydrophilic. Given that O2 is nonpolar, the increased hydrophobicity at the iron center of the binary complex appears to be essential for rapid O2 binding and activation, explaining the reason for the 3-HAA-induced loop movements. Because substrate binding-induced open-to-closed conformational changes are common, the results reported here may help further our understanding of how oxygen is enriched in nonheme iron-dependent dioxygenases. PMID- 29784878 TI - Oxidative decarboxylation of pyruvate by 1-deoxy-d-xyulose 5-phosphate synthase, a central metabolic enzyme in bacteria. AB - The underexploited antibacterial target 1-deoxy-d-xyluose 5-phosphate (DXP) synthase catalyzes the thiamin diphosphate (ThDP)-dependent formation of DXP from pyruvate and d-glyceraldehyde 3-phosphate (d-GAP). DXP is an essential intermediate in the biosynthesis of ThDP, pyridoxal phosphate, and isoprenoids in many pathogenic bacteria. DXP synthase catalyzes a distinct mechanism in ThDP decarboxylative enzymology in which the first enzyme-bound pre-decarboxylation intermediate, C2alpha-lactyl-ThDP (LThDP), is stabilized by DXP synthase in the absence of d-GAP, and d-GAP then induces efficient LThDP decarboxylation. Despite the observed LThDP accumulation and lack of evidence for C2alpha-carbanion formation in the absence of d-GAP, CO2 is released at appreciable levels under these conditions. Here, seeking to resolve these conflicting observations, we show that DXP synthase catalyzes the oxidative decarboxylation of pyruvate under conditions in which LThDP accumulates. O2-dependent LThDP decarboxylation led to one-electron transfer from the C2alpha-carbanion/enamine to O2, with intermediate ThDP-enamine radical formation, followed by peracetic acid formation en route to acetate. Thus, LThDP formation and decarboxylation and DXP formation were studied under anaerobic conditions. Our results support a model in which O2-dependent LThDP decarboxylation and peracetic acid formation occur in the absence of d-GAP, decreasing the levels of pyruvate and O2 in solution. The relative pyruvate and O2 concentrations then dictate the extent of LThDP accumulation, and its buildup can be observed when [pyruvate] > [O2]. The finding that O2 acts as a structurally distinct trigger of LThDP decarboxylation supports the hypothesis that a mechanism involving small molecule-dependent LThDP decarboxylation equips DXP synthase for diverse, yet uncharacterized cellular functions. PMID- 29784879 TI - ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing alpha-mannosidase-like protein 3 (EDEM3). AB - Protein folding in the cell is regulated by several quality-control mechanisms. Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway. In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins. The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing alpha-mannosidase like proteins (EDEMs). However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3. This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 alpha-mannosidase domain. In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor alpha locus (TCRalpha), was reconstituted only when ERp46 had established a covalent interaction with EDEM3. On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER. PMID- 29784880 TI - Arginine methylation of translocated in liposarcoma (TLS) inhibits its binding to long noncoding RNA, abrogating TLS-mediated repression of CBP/p300 activity. AB - Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized. Herein, using various biochemical assays, we confirmed the earlier observations that TLS is methylated by protein arginine methyltransferase 1 (PRMT1) in vitro The arginine methylation of TLS disrupted binding to pncRNA and also prevented binding of TLS to and inhibition of CBP/p300. This result indicated that arginine methylation of TLS abrogates both binding to pncRNA and TLS-mediated inhibition of CBP/p300 HAT activities. We also report that an arginine residue within the Arg-Gly-Gly domain of TLS, Arg-476, serves as the major determinant for binding to pncRNA. Either methylation or mutation of Arg-476 of TLS significantly decreased pncRNA binding and thereby prevented a pncRNA-induced allosteric alteration in TLS that is required for its interaction with CBP/p300. Moreover, unlike WT TLS, an R476A TLS mutant did not inhibit CCND1 promoter activity in luciferase reporter assays. Taken together, we propose the hypothesis that arginine methylation of TLS regulates both TLS-nucleic acid and TLS-protein interactions and thereby participates in transcriptional regulation. PMID- 29784881 TI - Structural basis for ADP-dependent glucokinase inhibition by 8-bromo-substituted adenosine nucleotide. AB - In higher eukaryotes, several ATP-utilizing enzymes known as hexokinases activate glucose in the glycolysis pathway by phosphorylation to glucose 6-phosphate. In contrast to canonical hexokinases, which use ATP, ADP-dependent glucokinase (ADPGK) catalyzes noncanonical phosphorylation of glucose to glucose 6-phosphate using ADP as a phosphate donor. Initially discovered in Archaea, the human homolog of ADPGK was described only recently. ADPGK's involvement in modified bioenergetics of activated T cells has been postulated, and elevated ADPGK expression has been reported in various cancer tissues. However, the physiological role of ADPGK is still poorly understood, and effective ADPGK inhibitors still await discovery. Here, we show that 8-bromo-substituted adenosine nucleotide inhibits human ADPGK. By solving the crystal structure of archaeal ADPGK in complex with 8-bromoadenosine phosphate (8-Br-AMP) at 1.81 A resolution, we identified the mechanism of inhibition. We observed that 8-Br-AMP is a competitive inhibitor of ADPGK and that the bromine substitution induces marked structural changes within the protein's active site by engaging crucial catalytic residues. The results obtained using the Jurkat model of activated human T cells suggest its moderate activity in a cellular setting. We propose that our structural insights provide a critical basis for rational development of novel ADPGK inhibitors. PMID- 29784882 TI - Phenotypic Assessment Suggests Multiple Start Codons for HetN, an Inhibitor of Heterocyst Differentiation, in Anabaena sp. Strain PCC 7120. AB - Multicellular organisms must carefully regulate the timing, number, and location of specialized cellular development. In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, nitrogen-fixing heterocysts are interspersed between vegetative cells in a periodic pattern to achieve an optimal exchange of bioavailable nitrogen and reduced carbon. The spacing between heterocysts is regulated by the activity of two developmental inhibitors, PatS and HetN. PatS functions to create a de novo pattern from a homogenous field of undifferentiated cells, while HetN maintains the pattern throughout subsequent growth. Both PatS and HetN harbor the peptide motif ERGSGR, which is sufficient to inhibit development. While the small size of PatS makes the interpretation of inhibitory domains relatively simple, HetN is a 287-amino-acid protein with multiple functional regions. Previous work suggested the possibility of a truncated form of HetN containing the ERGSGR motif as the source of the HetN-derived inhibitory signal. In this work, we present evidence that the glutamate of the ERGSGR motif is required for proper HetN inhibition of heterocysts. Mutational analysis and subcellular localization indicate that the gene encoding HetN uses two methionine start codons (M1 and M119) to encode two protein forms: M1 is required for protein localization, while M119 is primarily responsible for inhibitory function. Finally, we demonstrate that patS and hetN are not functionally equivalent when expressed from the other gene's regulatory sequences. Taken together, these results help clarify the functional forms of HetN and will help refine future work defining a HetN-derived inhibitory signal in this model of one dimensional periodic patterning.IMPORTANCE The proper placement of different cell types during a developmental program requires the creation and maintenance of a biological pattern to define the cells that will differentiate. Here we show that the HetN inhibitor, responsible for pattern maintenance of specialized nitrogen fixing heterocyst cells in the filamentous cyanobacterium Anabaena, may be produced from two different start methionine codons. This work demonstrates that the two start sites are individually involved in a different HetN function, either membrane localization or inhibition of cellular differentiation. PMID- 29784883 TI - Cytochrome bd Oxidase Has an Important Role in Sustaining Growth and Development of Streptomyces coelicolor A3(2) under Oxygen-Limiting Conditions. AB - Streptomyces coelicolor A3(2) is a filamentously growing, spore-forming, obligately aerobic actinobacterium that uses both a copper aa3 -type cytochrome c oxidase and a cytochrome bd oxidase to respire oxygen. Using defined knockout mutants, we demonstrated that either of these terminal oxidases was capable of allowing the bacterium to grow and complete its developmental cycle. The genes encoding the bcc complex and the aa3 oxidase are clustered at a single locus. Using Western blot analyses, we showed that the bcc-aa3 oxidase branch is more prevalent in spores than the bd oxidase. The level of the catalytic subunit, CydA, of the bd oxidase was low in spore extracts derived from the wild type, but it was upregulated in a mutant lacking the bcc-aa3 supercomplex. This indicates that cytochrome bd oxidase can compensate for the lack of the other respiratory branch. Components of both oxidases were abundant in growing mycelium. Growth studies in liquid medium revealed that a mutant lacking the bcc-aa3 oxidase branch grew approximately half as fast as the wild type, while the oxygen reduction rate of the mutant remained close to that of the wild type, indicating that the bd oxidase was mainly functioning in controlling electron flux. Developmental defects were observed for a mutant lacking the cytochrome bd oxidase during growth on buffered rich medium plates with glucose as the energy substrate. Evidence based on using the redox-cycling dye methylene blue suggested that cytochrome bd oxidase is essential for the bacterium to grow and complete its developmental cycle under oxygen limitation.IMPORTANCE Respiring with oxygen is an efficient means of conserving energy in biological systems. The spore forming, filamentous actinobacterium Streptomyces coelicolor grows only aerobically, synthesizing two enzyme complexes for O2 reduction, the cytochrome bcc-aa3 cytochrome oxidase supercomplex and the cytochrome bd oxidase. We show in this study that the bacterium can survive with either of these respiratory pathways to oxygen. Immunological studies indicate that the bcc-aa3 oxidase is the main oxidase present in spores, but the bd oxidase compensates if the bcc-aa3 oxidase is inactivated. Both oxidases are active in mycelia. Growth conditions were identified, revealing that cytochrome bd oxidase is essential for aerial hypha formation and sporulation, and this was linked to an important role of the enzyme under oxygen-limiting conditions. PMID- 29784884 TI - Effector Gene xopAE of Xanthomonas euvesicatoria 85-10 Is Part of an Operon and Encodes an E3 Ubiquitin Ligase. AB - The type III effector XopAE from the Xanthomonas euvesicatoria strain 85-10 was previously shown to inhibit plant immunity and enhance pathogen-induced disease symptoms. Evolutionary analysis of 60 xopAE alleles (AEal) revealed that the xopAE locus is conserved in multiple Xanthomonas species. The majority of xopAE alleles (55 out of 60) comprise a single open reading frame (ORF) (xopAE), while in 5 alleles, including AEal 37 of the X. euvesicatoria 85-10 strain, a frameshift splits the locus into two ORFs (hpaF and a truncated xopAE). To test whether the second ORF of AEal 37 (xopAE85-10 ) is translated, we examined expression of yellow fluorescent protein (YFP) fused downstream to truncated or mutant forms of the locus in Xanthomonas bacteria. YFP fluorescence was detected at maximal levels when the reporter was in proximity to an internal ribosome binding site upstream of a rare ATT start codon in the xopAE85-10 ORF but was severely reduced when these elements were abolished. In agreement with the notion that xopAE85-10 is a functional gene, its protein product was translocated into plant cells by the type III secretion system, and translocation was dependent on its upstream ORF, hpaF Homology modeling predicted that XopAE85-10 contains an E3 ligase XL box domain at the C terminus, and in vitro assays demonstrated that this domain displays monoubiquitination activity. Remarkably, the XL box was essential for XopAE85-10 to inhibit pathogen-associated molecular pattern (PAMP) induced gene expression in Arabidopsis protoplasts. Together, these results indicate that the xopAE85-10 gene resides in a functional operon, which utilizes the alternative start codon ATT and encodes a novel XL box E3 ligase.IMPORTANCEXanthomonas bacteria utilize a type III secretion system to cause disease in many crops. This study provides insights into the evolution, translocation, and biochemical function of the XopAE type III secreted effector, contributing to the understanding of Xanthomonas-host interactions. We establish XopAE as a core effector of seven Xanthomonas species and elucidate the evolution of the Xanthomonas euvesicatoriaxopAE locus, which contains an operon encoding a truncated effector. Our findings indicate that this operon evolved from the split of a multidomain gene into two ORFs that conserved the original domain function. Analysis of xopAE85-10 translation provides the first evidence for translation initiation from an ATT codon in Xanthomonas Our data demonstrate that XopAE85-10 is an XL box E3 ubiquitin ligase and provide insights into the structure and function of this effector family. PMID- 29784885 TI - Pseudomonas aeruginosa Regulated Intramembrane Proteolysis: Protease MucP Can Overcome Mutations in the AlgO Periplasmic Protease To Restore Alginate Production in Nonmucoid Revertants. AB - The progression of cystic fibrosis (CF) from an acute to a chronic disease is often associated with the conversion of the opportunistic pathogen Pseudomonas aeruginosa from a nonmucoid form to a mucoid form in the lung. This conversion involves the constitutive synthesis of the exopolysaccharide alginate, whose production is under the control of the AlgT/U sigma factor. This factor is regulated posttranslationally by an extremely unstable process and has been commonly attributed to mutations in the algT (algU) gene. By exploiting this unstable phenotype, we isolated 34 spontaneous nonmucoid variants arising from the mucoid strain PDO300, a PAO1 derivative containing the mucA22 allele commonly found in mucoid CF isolates. Complementation analysis using a minimal tiling path cosmid library revealed that most of these mutants mapped to two protease encoding genes, algO, also known as prc or PA3257, and mucP Interestingly, our algO mutations were complemented by both mucP and algO, leading us to delete, clone, and overexpress mucP, algO, mucE, and mucD in both wild-type PAO1 and PDO300 backgrounds to better understand the regulation of this complex regulatory mechanism. Our findings suggest that the regulatory proteases follow two pathways for regulated intramembrane proteolysis (RIP), where both the AlgO/MucP pathway and MucE/AlgW pathway are required in the wild-type strain but where the AlgO/MucP pathway can bypass the MucE/AlgW pathway in mucoid strains with membrane-associated forms of MucA with shortened C termini, such as the MucA22 variant. This work gives us a better understanding of how alginate production is regulated in the clinically important mucoid variants of Pseudomonas aeruginosaIMPORTANCE Infection by the opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality seen in CF patients. Poor patient prognosis correlates with the genotypic and phenotypic change of the bacteria from a typical nonmucoid to a mucoid form in the CF lung, characterized by the overproduction of alginate. The expression of this exopolysaccharide is under the control an alternate sigma factor, AlgT/U, that is regulated posttranslationally by a series of proteases. A better understanding of this regulatory phenomenon will help in the development of therapies targeting alginate production, ultimately leading to an increase in the length and quality of life for those suffering from CF. PMID- 29784886 TI - Legionella pneumophila Is Directly Sensitive to 2-Deoxyglucose-Phosphate via Its UhpC Transporter but Is Indifferent to Shifts in Host Cell Glycolytic Metabolism. AB - Toll-like receptor (TLR) stimulation induces a pronounced shift to increased glycolytic metabolism in mammalian macrophages. We observed that bone marrow derived macrophages (BMMs) increase glycolysis in response to infection with Legionella pneumophila, but the role of host macrophage glycolysis in terms of intracellular L. pneumophila replication is not currently understood. Treatment with 2-deoxyglucose (2DG) blocks L. pneumophila replication in mammalian macrophages but has no effect on bacteria grown in broth. In addition, we found that 2DG had no effect on bacteria grown in amoebae. We used a serial enrichment strategy to reveal that the effect of 2DG on L. pneumophila in macrophages requires the L. pneumophila hexose-phosphate transporter UhpC. Experiments with UhpC-deficient L. pneumophila revealed that mutant bacteria are also resistant to growth inhibition following treatment with phosphorylated 2DG in broth, suggesting that the inhibitory effect of 2DG on L. pneumophila in mammalian cells requires 2DG phosphorylation. UhpC-deficient L. pneumophila replicates without a growth defect in BMMs and protozoan host cells and also replicates without a growth defect in BMMs treated with 2DG. Our data indicate that neither TLR signaling-dependent increased macrophage glycolysis nor inhibition of macrophage glycolysis has a substantial effect on intracellular L. pneumophila replication. These results are consistent with the view that L. pneumophila can employ diverse metabolic strategies to exploit its host cells.IMPORTANCE We explored the relationship between macrophage glycolysis and replication of an intracellular bacterial pathogen, Legionella pneumophila Previous studies demonstrated that a glycolysis inhibitor, 2-deoxyglucose (2DG), blocks replication of L. pneumophila during infection of macrophages, leading to speculation that L. pneumophila may exploit macrophage glycolysis. We isolated L. pneumophila mutants resistant to the inhibitory effect of 2DG in macrophages, identifying a L. pneumophila hexose phosphate transporter, UhpC, that is required for bacterial sensitivity to 2DG during infection. Our results reveal how a bacterial transporter mediates the direct antimicrobial effect of a toxic metabolite. Moreover, our results indicate that neither induction nor impairment of host glycolysis inhibits intracellular replication of L. pneumophila, which is consistent with a view of L. pneumophila as a metabolic generalist. PMID- 29784887 TI - Identification of the Thioredoxin Partner of Vitamin K Epoxide Reductase in Mycobacterial Disulfide Bond Formation. AB - Disulfide bonds influence the stability and activity of many proteins. In Escherichia coli, the DsbA and DsbB enzymes promote disulfide bond formation. Other bacteria, including the Actinobacteria, use instead of DsbB the enzyme vitamin K epoxide reductase (VKOR), whose gene is found either fused to or in the same operon as a dsbA-like gene. Mycobacterium tuberculosis and other Gram positive actinobacteria secrete many proteins with even numbers of cysteines to the cell envelope. These organisms have predicted oxidoreductases and VKOR orthologs. These findings indicate that such bacteria likely form disulfide bonds in the cell envelope. The M. tuberculosisvkor gene complements an E. colidsbB deletion strain, restoring the oxidation of E. coli DsbA. While we have suggested that the dsbA gene linked to the vkor gene may express VKOR's partner in mycobacteria, others have suggested that two other extracytoplasmic oxidoreductases (DsbE or DsbF) may be catalysts of protein disulfide bond formation. However, there is no direct evidence for interactions of VKOR with either DsbA, DsbE, or DsbF. To identify the actual substrate of VKOR, we identified two additional predicted extracytoplasmic DsbA-like proteins using bioinformatics analysis of the M. tuberculosis genome. Using the five potential DsbAs, we attempted to reconstitute disulfide bond pathways in E. coli and in Mycobacterium smegmatis, a close relative of M. tuberculosis Our results show that only M. tuberculosis DsbA is oxidized by VKOR. Comparison of the properties of dsbA- and vkor-null mutants in M. smegmatis shows parallels to the properties of dsb mutations in E. coliIMPORTANCE Disulfide bond formation has a great impact on bacterial pathogenicity. Thus, disulfide-bond-forming proteins represent new targets for the development of antibacterials, since the inhibition of disulfide bond formation would result in the simultaneous loss of the activity of several classes of virulence factors. Here, we identified five candidate proteins encoded by the M. tuberculosis genome as possible substrates of the M. tuberculosis VKOR protein involved in disulfide bond formation. We then reconstituted the mycobacterial disulfide bond formation pathway in E. coli and showed that of the five candidates, only M. tuberculosis DsbA is efficiently oxidized by VKOR in E. coli We also present evidence for the involvement of VKOR in DsbA oxidation in M. smegmatis. PMID- 29784888 TI - Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis. AB - Breast cancer brain metastases remain largely incurable. Although several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immunocompromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. As seen by immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain. In vitro assays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sites in vivo, and potent radio-sensitising properties in vitro The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis.This article has an associated First Person interview with Soo-Hyun Kim, joint first author of the paper. PMID- 29784890 TI - Assessment of the Efficacy of Physical Activity Level and Lifestyle Behavior Interventions Applying Social Cognitive Theory for Overweight and Obese Girl Adolescents. AB - BACKGROUND: Childhood obesity has become a global epidemic and physical inactivity and considered as one of the most important contributing factors. We aimed to evaluate a school-based physical activity intervention using social cognitive theory (SCT) to increase physical activity behavior in order to prevent obesity among overweight and obese adolescent girls. STUDY DESIGN: Randomized controlled trial study. METHODS: A seven-month randomized controlled trial based on SCT was implemented with 172 overweight and obese girl students (87 in intervention and 85 in control group), with the presence of their parents and teachers. Activities of the trial included: Sports workshops, physical-activity consulting private sessions, free practical and competitive sports sessions, family exercise sessions, text messages, and newsletters. Body Mass Index (BMI) and Waist Circumference (WC) were measured and questionnaires about duration of physical activity, duration of screen time (watching television and playing computer games) and psychological variables regarding the SCT constructs were obtained. RESULTS: Duration of physical activity (in minutes) and most of psychological variables (self-efficacy, social support, and intention) significantly increased at post-intervention, while hours of watching television and playing computer were significantly decreased (P<0.001). The subjects' mean BMI and WC reduced in the intervention group from 29.47 (4.05) kg/m2 to 28.5 (4.35) kg/m2 and 89.65 (8.15) cm to 86.54 (9.76) cm, although they were not statistically significant compared with the control group (P=0.127 and P=0.504, respectively). CONCLUSIONS: School-based intervention using SCT led to an increase in the duration of physical activity and reduction in the duration of screen time in overweight and obese adolescent girls. PMID- 29784889 TI - SINHCAF/FAM60A and SIN3A specifically repress HIF-2alpha expression. AB - The SIN3A-HDAC (histone deacetylase) complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF (SIN3A and HDAC-associated factor)/FAM60A (family of homology 60A), links the SIN3A-HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically represses HIF-2alpha mRNA and protein expression, via its interaction with the transcription factor SP1 (specificity protein 1) and recruitment of HDAC1 to the HIF-2alpha promoter. SINHCAF control over HIF-2alpha results in functional cellular changes in in vitro angiogenesis and viability. Our analysis reveals an unexpected link between SINHCAF and the regulation of the hypoxia response. PMID- 29784891 TI - Predicting Physical Activity Behavior in African American Females: Using Multi Theory Model. AB - BACKGROUND: Despite physical activity having several benefits, a considerable number of Americans do not engage in sufficient exercise. Among the high-risk groups are African American women. A recent theory, multi theory model (MTM) for health behavior change can be used to develop effective interventions. The objective of this research was to test MTM in its ability to predict physical activity behavior in African American women. STUDY DESIGN: A cross-sectional study. METHODS: African American women aged 18 yr and older were recruited at various locations (primarily churches) of Jackson, a large city in southern Mississippi to participate in this cross-sectional study in 2016. The valid and reliable survey was administered to a G*Power calculated quota sample of 156 women either in person or via a Qualtrics link sent through an e-mail. RESULTS: The regression analysis revealed that 32.7% of the variance in initiating physical activity behavior was predicted by participatory dialogue, behavioral confidence, and changes in physical environment. Sustenance of physical activity behavior was predicted up to 38.8% by emotional transformation and changes in social environment. CONCLUSIONS: MTM appears to be a robust theory in its application for changing physical activity behavior in African American women. This theory must be reified and empirically tested with this population. PMID- 29784892 TI - Food Insecurity and Primary School Girl Students' Intelligence Quotients: A Case Control Study. AB - BACKGROUND: Food insecurity (FI) refers to the lack of sufficient and safe availability of the food. Accumulating studies have suggested associations between dietary intake and Intelligence quotient (IQ). Accordingly, we aimed to examine the association between FI and IQ. STUDY DESIGN: Case-control study. METHODS: In this case-control study, 222 girl students aged 9 to 11 years old were randomly chosen from Bandar-Anzali, Iran in 2013. Students with low and moderate IQ were considered as case (n=111) and control (n=111) group, respectively. General and demographic characteristics were collected using interview. United States Department of Agriculture (USDA) household FI questionnaires were also completed. To determine IQ, Wechsler's revised intelligence test was used. RESULTS: FI was observed in 51% of study participants. The prevalence of FI in case and control group was 58.6% and 22.5%, respectively. The mean IQ was 77.97 +/-5.56 in case and 94.6 +/-5.47 for control group. It was found that there was an inverse association between FI and low IQ. The results of the multiple variable logistic regression analysis (odds ratio and its 95% confidence interval) showed that, FI 3.46 (1.85, 6.50; P>0.001), natural type of delivery 2.45 (1.30, 4.62; P=0.006), and father's low education level 2.97 (1.43, 6.19; P=0.004) were the risky factors leading to low IQ. CONCLUSIONS: There was an inverse link between FI and IQ. Therefore, it is necessary to pay more attention to FI and its consequences, particularly in mental health of children. PMID- 29784893 TI - A Comparison between Decision Tree and Random Forest in Determining the Risk Factors Associated with Type 2 Diabetes. AB - BACKGROUND: We aimed to identify the associated risk factors of type 2 diabetes mellitus (T2DM) using data mining approach, decision tree and random forest techniques using the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) Study program. STUDY DESIGN: A cross-sectional study. METHODS: The MASHAD study started in 2010 and will continue until 2020. Two data mining tools, namely decision trees, and random forests, are used for predicting T2DM when some other characteristics are observed on 9528 subjects recruited from MASHAD database. This paper makes a comparison between these two models in terms of accuracy, sensitivity, specificity and the area under ROC curve. RESULTS: The prevalence rate of T2DM was 14% among these subjects. The decision tree model has 64.9% accuracy, 64.5% sensitivity, 66.8% specificity, and area under the ROC curve measuring 68.6%, while the random forest model has 71.1% accuracy, 71.3% sensitivity, 69.9% specificity, and area under the ROC curve measuring 77.3% respectively. CONCLUSIONS: The random forest model, when used with demographic, clinical, and anthropometric and biochemical measurements, can provide a simple tool to identify associated risk factors for type 2 diabetes. Such identification can substantially use for managing the health policy to reduce the number of subjects with T2DM . PMID- 29784894 TI - Self-Reported and Network Scale-Up Estimates of Substance Use Prevalence among University Students in Kerman, Iran. AB - BACKGROUND: This study aimed to estimate the prevalence of substance use among university students measured by direct and indirect methods, and to calculate the visibility factor (VF) defined as ratio of indirect to direct estimates of substance use prevalence. STUDY DESIGN: A cross-sectional study. METHODS: Using a multistage non-random sampling approach, we recruited 2157 students from three universities in Kerman, Iran, in 2016. We collected data on substance use by individual face-to-face interview using direct (i.e. self-report of their own behaviors) and indirect (NSU: Network scale up) methods. All estimates from direct and indirect methods were weighted based on inverse probability weight of sampling university. RESULTS: The response rate was 83.6%. The last year prevalence of water pipe, alcohol, and cigarettes indirect method was 44.6%, 18.1%, and 13.2% respectively. Corresponding figures in NSU analysis were 36.4%, 18.2%, and 16.5% respectively. In the female population, VF for all types of substance was less than male. CONCLUSIONS: Considerable numbers of university students used substances like a water pipe, alcohol, and cigarettes. NSU seems a promising method, especially among male students. Among female students, direct method provided more reliable results mainly due to transmission and prestige biases. PMID- 29784895 TI - Bullying Among Tunisian Middle School Students: the Prevalence, Psychosocial Associated Factors and Perceived Involvement of Parents, Teachers and Classmates. AB - BACKGROUND: Bullying is a serious public health concern remarkably common among youth. Involvement in bullying can lead to deleterious effect on the emotional well-being of pupils. The aim of this study was to assess the prevalence of bullying, its psychosocial associated factors and the perceived involvement of parents, teachers, and classmates to counteract this behavior. STUDY DESIGN: A cross-sectional study. METHODS: We conducted this study in 2015 among a representative multistage sample of 1584 students enrolled in middle schools in the Region of Sousse using the revised Olweus Bully/Victim Questionnaire. It assesses the prevalence of bullying and covers qualitative details of bullying including psychosocial factors and perceived efforts of others to counteract bullying. RESULTS: 11.7% of respondents were classified as pure victims, 7.8% as pure bullies, 3.2% as bully-victims and 75.5% as bystanders. Compared to other groups, the bully-victims were less likely to report a feeling of empathy and liking school. They were more likely to be afraid of being bullied, aggressive and to have fewer friends in the class. Only 30.3% of the victims indicated that they told someone about being bullied. The majority of the middle school students perceived that classmates (54.1%) and teachers (39.5%) did nothing to counteract bullying. CONCLUSIONS: Information about bullying is critical and must be gathered before effective intervention is planned. Parents, teachers and students should learn effective ways to handle the bullying problem since the most effective programs are comprehensive targeting students, schools, families and the community. PMID- 29784896 TI - Measuring and Explaining Socioeconomic Inequalities in Public Healthcare Utilization in Western Iran: Evidence from a Cross-sectional Survey. AB - BACKGROUND: Equity in healthcare utilization is a major health policy goal in all healthcare systems. This study aimed to examine socioeconomic inequalities in public healthcare utilization in Kermanshah City, western Iran. STUDY DESIGN: A cross-sectional study. METHODS: Using convenience sampling method, 2040 adult aged 18-65 yr were enrolled from Kermanshah City in 2017. A self-administrated questionnaire was used to collect data on socio-demographic characteristics, socioeconomic status, behavioral factors, and utilization of public healthcare services (inpatient and outpatient care) over the period between from May to Aug 2017. The concentration index (C) was used to measure and decompose socioeconomic inequalities in the utilization inpatient and outpatient care in public sector. The indirect standardization method was used to estimate the horizontal inequity (HI) indices in inpatient and outpatient care use. RESULTS: The utilization outpatient (C=-0.121, 95% CI: -0.171, -0.071) and inpatient care in public sector (C=-0.165, 95% CI: -0.229, -0.101) were concentrated among the poor in Kermanshah, Iran. Socioeconomic status, health-related quality of life, marital status and having a chronic health condition were the main determinants of socioeconomic-related inequalities in the utilization of inpatient and outpatient care in public sector among adults. The distributions of outpatient (HI=-0.045, CI: -0.093 to 0.003) and inpatient care (HI= -0.044 95% CI: -0.102, 0.014) in Kermanshah were pro-poor. These results were not statistically significant (P<0.05). CONCLUSIONS: The utilization of public healthcare services in Iran are pro-poor. The pro-poor distribution of inpatient and outpatient care in public facilities calls for initiatives to increase the allocation of resources to public facilities in Iran that may greatly benefit the health outcomes of the poor. PMID- 29784897 TI - Effect of Alcohol Use on Injection and Sexual Behavior among People Who Inject Drugs in Tehran, Iran: A Coarsened Exact Matching Approach. AB - BACKGROUND: Many studies have recognized the importance of sexual and injection risk behaviors in HIV transmission among people who inject drugs (PWID). We aimed to examine effect of alcohol use on sexual and injection risky behavior using coarsened exact matching (CEM) approach among PWID in Tehran, Iran. STUDY DESIGN: A cross-sectional study. METHODS: This study was conducted from Mar to Aug 2016 in Tehran, Iran. PWID were recruited by a convenience and snowball sampling from five of Drop-in Centers (DICs) in Tehran. We assessed three outcomes of interest, all treated as binary variables, including distributive and receptive sharing and inconsistent condom use with any type of sexual partner. We applied coarsened exact matching (CEM) to estimate the independent effect of alcohol use on injection and sexual risk behaviours. All data analysis was performed using Stata v.11. RESULTS: Overall, 550 PWID (all male) were enrolled. The prevalence of receptive sharing, distributive sharing, and inconsistent condom use was 32%, 15% and 55%, respectively. In the matched samples, last month drinkers were more likely to report receptive sharing (OR=2.12 95% CI: 1.31, 3.81; P=0.022), as compared to abstainer participants. Distributive sharing in last 30 d, was also significantly higher among last month drinkers group (OR=2.72 95% CI 1.72, 4.21; P=0.011), compared last month abstainers group. Finally, there was a statistically significant relationship between alcohol use and inconsistent condom use (OR=4.21 95% CI: 2.71, 7.52; P=0.013). CONCLUSIONS: The findings emphasize importance of addressing alcohol use in risk reduction interventions for Iranian PWID with alcohol use. PMID- 29784898 TI - Pretreatment with simvastatin upregulates expression of BK-2R and CD11b in the ischemic penumbra of rats. AB - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment in preventing cerebral ischemia/reperfusion injury in rats using a model of middle cerebral artery occlusion (MCAO). Rats were pretreated with simvastatin 14 days prior to MCAO induction. At 3, 24, and 48 hours after reperfusion, bradykinin levels in the ischemic penumbra were assayed by ELISA, mRNA levels of bradykinin B2 receptors (BK-2Rs) and CD11b were measured by fluorescent quantitative real-time PCR (RT-PCR), and co-expression of microglia and BK-2Rs was determined by immunofluorescence. Simvastatin had no effect on bradykinin expression in the ischemic penumbra at any time point. However, the levels of BK-2R and CD11b mRNA in the ischemic penumbra, which were significantly decreased 3 hours after ischemia-reperfusion, were increased in simvastatin-pretreated rats. Moreover, the co-expression of BK-2Rs and microglia was confirmed by immunofluorescence analysis. These results suggest that the beneficial effects of simvastatin pretreatment before cerebral ischemia/reperfusion injury in rats may be partially due to increased expression of BK-2R and CD11b in the ischemic penumbra. PMID- 29784899 TI - Pathway-based analysis of genome-wide association study of circadian phenotypes. AB - Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms (SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies (GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime, totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration. PMID- 29784900 TI - IRAK Inhibitor Protects the Intestinal Tract of Necrotizing Enterocolitis by Inhibiting the Toll-Like Receptor (TLR) Inflammatory Signaling Pathway in Rats. AB - BACKGROUND The aim of this study was to assess the effects of interleukin-1 (IL 1) receptor associated kinase (IRAK) inhibitors on intestinal injury induced by necrotizing enterocolitis (NEC) in neonatal rats and its regulation on the intestinal Toll-like receptor (TLR) inflammatory signaling pathway. MATERIAL AND METHODS The neonatal rat models of NEC were established though hypoxia-cold stimulation. All rats were divided into 3 groups: an NEC model group (NEC group), an IRAK inhibitor group (IRAKI group), and a normal control group (NC group). At 72 h after the models were established, intestinal tissues were collected for histopathological examination, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. RESULTS After IRAK inhibitor intervention, the symptoms of NEC in neonatal rats were alleviated, and the degree of weight loss was reduced. In the IRAK group, the intestinal pathology of neonatal rats was improved, pathological score was decreased, and the incidence rate of NEC was significantly reduced. The levels of tumor necrosis factor-alpha (TNF-alpha), IL 1beta, and IL-6 in the IRAK group were significantly decreased compared with those in the NEC group. There were no significant differences in IRAK1 and IRAK4 protein expression levels between the IRAK group and the NEC group. The phosphorylated IRAK1 and IRAK4 in the IRAK group were significantly decreased. Nuclear factor-kappa B (NF-kappaB) level of intestinal tissues in the IRAK group was reduced compared with that in the NEC group. CONCLUSIONS IRAK inhibitors can inhibit the inflammatory response of the NEC model, reduce the release of pro inflammatory cytokines, and alleviate the damage to intestinal tissues by inhibiting conduction of the TLR signaling pathway. PMID- 29784901 TI - Symptomatic Total Aortic Occlusion. AB - BACKGROUND Aortic occlusion, whether acute or subacute, is a rare but very serious entity with disastrous consequences if not treated in a timely fashion. Rapid diagnosis is crucial in this setting. In surgically treated patients there is a high degree of mortality and morbidity; therefore, percutaneous revascularization, whenever possible and independent of the available techniques, is much more desirable. CASE REPORT A 62-year-old woman with a history of diabetes mellitus, dyslipidemia, hypertension, and peripheral vascular disease, with previous femoral-femoral bypass for right common iliac artery occlusion, and with recent conventional angiography showing near occlusion of the ostial left common iliac artery (the donor vessel for the previous bypass), was referred to our hospital for conventional angioplasty. We faced were surprised to find a total infrarenal aortic occlusion and decided to perform emergency and rescue recanalization. We successfully recanalized the aorta and left iliac artery by stent implantation and stabilized the patient, considering that surgical intervention has very high risk for morbidity and mortality in this particular setting. CONCLUSIONS Although revascularization is rarely performed in this life threating condition, endovascular recanalization of a subacute aortic occlusion in a patient with femoral-femoral bypass is feasible and can be life-saving. PMID- 29784902 TI - Physician Practice Patterns and Barriers to Counselling on Physical Activity in Solid Organ Transplant Recipients. AB - BACKGROUND Many solid organ transplant (SOT) recipients fail to meet the recommended physical activity (PA) levels. "Physician recommendation" has previously been reported by SOT recipients as a key facilitator to being more physically active. The purpose of this study was to determine the proportion of Canadian SOT physicians providing PA counselling and identify barriers to including such counselling as part of the SOT recipients' routine care. MATERIAL AND METHODS We conducted a cross-sectional web-based survey study to evaluate physicians' PA counselling practices, including the prevalence and barriers to such practice. A survey link was sent to a convenience sample of transplant physicians who are members of the Canadian Society of Transplantation. RESULTS Thirty-four physicians (13.6%) participated in the survey. While 97% (n=33) of the participants reported providing PA counselling to their transplant patients, only 18% (n=6) responded they were very confident in PA counselling. Lack of time (n=19; 56%) and a lack of exercise guidelines (n=18; 53%) were identified as the main barriers to PA counselling. CONCLUSIONS Incorporating sufficient PA knowledge into physicians' educational curricula system, developing specific PA guidelines as well as establishing an easier referral system to exercise specialists might improve the frequency and quality of PA counselling post transplant. PMID- 29784903 TI - Exercise ameliorates endoplasmic reticulum stress-mediated vascular dysfunction in mesenteric arteries in atherosclerosis. AB - Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis, but the effects of exercise on ER stress-mediated endothelial dysfunction in atherosclerosis is not yet fully understood. We assessed endothelium-dependent vasodilation in isolated mesenteric arteries from wild type (WT), WT with exercise (WT-EX), ApoE knockout (ApoE KO), and ApoE KO mice with exercise (ApoE KO-EX). Vasodilation to acetylcholine (ACh) was elicited in the presence of inhibitors of ER stress, eNOS, caspase-1, and UCP-2 (Tudca, L-NAME, AC-YVARD-cmk, and Genipin, respectively) and the ER stress inducer (Tunicamycin). Immunofluorescence was used to visualize the expression of CHOP, as an indicator of ER stress, in superior mesenteric arteries (SMA). Dilation to ACh was attenuated in ApoE KO but was improved in ApoE KO-EX. Incubation of Tudca and AC YVARD-cmk improved ACh-induced vasodilation in ApoE KO. L-NAME, tunicamycin, and Genipin attenuated vasodilation in WT, WT-EX and ApoE KO-EX, but not in ApoE KO. Exercise training reversed the increase in CHOP expression in the endothelium of SMA of ApoE KO mice. We conclude that ER stress plays a significant role in endothelial dysfunction of resistance arteries in atherosclerosis and that exercise attenuates ER stress and regulates its critical downstream signaling pathways including eNOS, UCP-2 and caspase-1. PMID- 29784904 TI - Differential protein profiling as a potential multi-marker approach for obese patients with heart failure: A retrospective study. AB - Identification of novel circulating biomarkers predicting death and major cardio metabolic events in obese patients with heart failure (HF) remains a research priority. In this study, we compared multi-marker profile of non-obese (NOB) and obese (OB) HF patients in relation to mortality outcome. The new multiplex proximity extension assay technology was used to analyze the levels of 92 proteins in plasma samples from HF patients according to body mass index (BMI) categories. At 2-year follow-up, all-cause mortality rates were significantly greater in NOB patients (BMI < 30 kg/m2) compared to the OB patients (BMI > 30 kg/m2) with HF (odds ratio 26; 95% CI: 1.14-624, p < 0,04). Quantitative proteomic analysis revealed thirteen distinct proteins expression profiles of OB and NOB HF patients. Among these proteins, RAGE, CXCL6, CXCL1, CD40, NEMO, VEGF A, KLK6, PECAM1, PAR1, MMP1, BNP and NTproBNP were down-regulated, whereas leptin was up-regulated in OB HF patients. In addition, an inverse correlation between plasma BNP levels and leptin in OB HF patients was observed (r = -0.58 p = 0.02). This study identifies specific plasma protein signature in OB and NOB patients with HF in relation to mortality outcome. PMID- 29784905 TI - Northward shift of the agricultural climate zone under 21st-century global climate change. AB - As agricultural regions are threatened by climate change, warming of high latitude regions and increasing food demands may lead to northward expansion of global agriculture. While socio-economic demands and edaphic conditions may govern the expansion, climate is a key limiting factor. Extant literature on future crop projections considers established agricultural regions and is mainly temperature based. We employed growing degree days (GDD), as the physiological link between temperature and crop growth, to assess the global northward shift of agricultural climate zones under 21st-century climate change. Using ClimGen scenarios for seven global climate models (GCMs), based on greenhouse gas (GHG) emissions and transient GHGs, we delineated the future extent of GDD areas, feasible for small cereals, and assessed the projected changes in rainfall and potential evapotranspiration. By 2099, roughly 76% (55% to 89%) of the boreal region might reach crop feasible GDD conditions, compared to the current 32%. The leading edge of the feasible GDD will shift northwards up to 1200 km by 2099 while the altitudinal shift remains marginal. However, most of the newly gained areas are associated with highly seasonal and monthly variations in climatic water balances, a critical component of any future land-use and management decisions. PMID- 29784906 TI - The anti-cancer activity of an andrographolide analogue functions through a GSK 3beta-independent Wnt/beta-catenin signaling pathway in colorectal cancer cells. AB - The Wnt/beta-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP 050), an andrographolide analogue and determine its activity in the Wnt/beta catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53. Furthermore, RS-PP-050 exerts inhibitory effects on beta-catenin transcription by suppressing T-cell factor/lymphocyte enhancer factor (TCF/LEF) activity in cells overexpressing beta-catenin and by down-regulating the endogenous expression of Wnt target genes. RS-PP-050 also decreased the protein expression of the active form of beta-catenin but functions independently of GSK-3beta, a negative regulator of Wnt. Interestingly, RS-PP-050 extensively blocks phosphorylation at Ser675 of beta-catenin which links to interference of the nuclear translocation of beta-catenin and might contribute to Wnt inactivation. Collectively, our findings reveal the underlying anti-cancer mechanism of an andrographolide analogue and provide useful insight for exploiting a newly chemotherapeutic agent in Wnt/beta-catenin-overexpressing CRC cells. PMID- 29784907 TI - A predictive model for risk of early grade >= 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial. AB - Infections are a major cause of death in patients with multiple myeloma. A post hoc analysis of the phase 3 FIRST trial was conducted to characterize treatment emergent (TE) infections and study risk factors for TE grade >= 3 infection. The number of TE infections/month was highest during the first 4 months of treatment (defined as early infection). Of 1613 treated patients, 340 (21.1%) experienced TE grade >= 3 infections in the first 18 months and 56.2% of these patients experienced their first grade >= 3 infection in the first 4 months. Risk of early infection was similar regardless of treatment. Based on the analyses of data in 1378 patients through multivariate logistic regression, a predictive model of first TE grade >= 3 infection in the first 4 months retained Eastern Cooperative Oncology Group performance status and serum beta2-microglobulin, lactate dehydrogenase, and hemoglobin levels to define high- and low-risk groups showing significantly different rates of infection (24.0% vs. 7.0%, respectively; P < 0.0001). The predictive model was validated with data from three clinical trials. This predictive model of early TE grade >= 3 infection may be applied in the clinical setting to guide infection monitoring and strategies for infection prevention. PMID- 29784910 TI - Consent for governance in the ethical use of organoids. PMID- 29784908 TI - Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses. AB - The immune response to pathogens varies substantially among people. Whereas both genetic and nongenetic factors contribute to interperson variation, their relative contributions and potential predictive power have remained largely unknown. By systematically correlating host factors in 534 healthy volunteers, including baseline immunological parameters and molecular profiles (genome, metabolome and gut microbiome), with cytokine production after stimulation with 20 pathogens, we identified distinct patterns of co-regulation. Among the 91 different cytokine-stimulus pairs, 11 categories of host factors together explained up to 67% of interindividual variation in cytokine production induced by stimulation. A computational model based on genetic data predicted the genetic component of stimulus-induced cytokine production (correlation 0.28-0.89), and nongenetic factors influenced cytokine production as well. PMID- 29784909 TI - Large quantum-spin-Hall gap in single-layer 1T' WSe2. AB - Two-dimensional (2D) topological insulators (TIs) are promising platforms for low dissipation spintronic devices based on the quantum-spin-Hall (QSH) effect, but experimental realization of such systems with a large band gap suitable for room temperature applications has proven difficult. Here, we report the successful growth on bilayer graphene of a quasi-freestanding WSe2 single layer with the 1T' structure that does not exist in the bulk form of WSe2. Using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we observe a gap of 129 meV in the 1T' layer and an in-gap edge state located near the layer boundary. The system's 2D TI characters are confirmed by first-principles calculations. The observed gap diminishes with doping by Rb adsorption, ultimately leading to an insulator-semimetal transition. The discovery of this large-gap 2D TI with a tunable band gap opens up opportunities for developing advanced nanoscale systems and quantum devices. PMID- 29784911 TI - Organoids test drug response. PMID- 29784912 TI - An update on organoid research. PMID- 29784913 TI - Modelling PDAC-niche adaption. PMID- 29784914 TI - A biobank for bladder cancer. PMID- 29784915 TI - Gene corrections in sight. PMID- 29784916 TI - Mammary lineage restriction in development. PMID- 29784917 TI - Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland. AB - Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer. PMID- 29784919 TI - Author Correction: Altered Cerebellar Biochemical Profiles in Infants Born Prematurely. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29784918 TI - Early lineage segregation of multipotent embryonic mammary gland progenitors. AB - The mammary gland is composed of basal cells and luminal cells. It is generally believed that the mammary gland arises from embryonic multipotent progenitors, but it remains unclear when lineage restriction occurs and what mechanisms are responsible for the switch from multipotency to unipotency during its morphogenesis. Here, we perform multicolour lineage tracing and assess the fate of single progenitors, and demonstrate the existence of a developmental switch from multipotency to unipotency during embryonic mammary gland development. Molecular profiling and single cell RNA-seq revealed that embryonic multipotent progenitors express a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in embryonic multipotent progenitors promotes unipotent basal cell fate and was sufficient to reprogram adult luminal cells into basal cells by promoting an intermediate hybrid multipotent-like state. Altogether, this study identifies the timing and the mechanisms mediating early lineage segregation of multipotent progenitors during mammary gland development. PMID- 29784920 TI - Video-rate volumetric neuronal imaging using 3D targeted illumination. AB - Fast volumetric microscopy is required to monitor large-scale neural ensembles with high spatio-temporal resolution. Widefield fluorescence microscopy can image large 2D fields of view at high resolution and speed while remaining simple and costeffective. A focal sweep add-on can further extend the capacity of widefield microscopy by enabling extended-depth-of-field (EDOF) imaging, but suffers from an inability to reject out-of-focus fluorescence background. Here, by using a digital micromirror device to target only in-focus sample features, we perform EDOF imaging with greatly enhanced contrast and signal-to-noise ratio, while reducing the light dosage delivered to the sample. Image quality is further improved by the application of a robust deconvolution algorithm. We demonstrate the advantages of our technique for in vivo calcium imaging in the mouse brain. PMID- 29784921 TI - The significance of deformation mechanisms on the fracture behavior of phase reversion-induced nanostructured austenitic stainless steel. AB - We describe here the relationship between grain structure, deformation mechanism and fracture characteristics in an austenitic stainless steel. This was accomplished using the novel concept of phase reversion that enabled a wide range of grain size from nanograined/ultrafine grained (NG/UFG) to coarse-grained (CG) regime to be obtained in a single material through change in temperature-time annealing sequence. In the NG/UFG structure, a marked increase in abundance of stacking faults (SFs) and twin density with strain was observed that led to a decrease in the average spacing between adjacent SFs, thus converting stacking faults into twins. Twinning in NG/UFG structure involved partial dislocations and their interaction with the grain boundaries, including SF overlapping and the coordinated nucleation of partial dislocations from the grain boundaries. The plastic zone in the NG/UFG structure resembled a network knitted by the intersecting twins and SFs. With SFE ~30 mJ/m2, the minimum stress for twin nucleation was ~250 MPa for the experiment steel and the corresponding optimal grain size (dop) wa ~120 nm. In contrast, in the CG structure, strain induced martensite formation was the deformation mechanism. The difference in the deformation mechanism led to a clear distinction in the fracture behavior from striated fracture in high strength-high ductility NG/UFG alloy to microvoid coalescence in the low strength-high ductility CG counterpart. The underlying reason for the change in fracture behavior was consistent with change in deformation mechanism from nanoscale twinning in NG/UFG alloy to strain-induced martensite in the CG alloy, which is related to change in the stability of austenite with grain size. An analysis of critical shear stress required to initiate twinning partial dislocations in comparison to that required to nucleate shear bands is presented. The appearance of striated fracture in the NG/UFG alloy suggests a quasi-static step wise crack growth process. PMID- 29784922 TI - Special temperatures in frustrated ferromagnets. AB - The description and detection of unconventional magnetic states, such as spin liquids, is a recurring topic in condensed matter physics. While much of the efforts have traditionally been directed at geometrically frustrated antiferromagnets, recent studies reveal that systems featuring competing antiferromagnetic and ferromagnetic interactions are also promising candidate materials. We find that this competition leads to the notion of special temperatures, analogous to those of gases, at which the competing interactions balance, and the system is quasi-ideal. Although induced by weak perturbing interactions, these special temperatures are surprisingly high and constitute an accessible experimental diagnostic of eventual order or spin-liquid properties. The well characterised Hamiltonian and extended low-temperature susceptibility measurement of the canonical frustrated ferromagnet Dy2Ti2O7 enables us to formulate both a phenomenological and microscopic theory of special temperatures for magnets. Other members of this class of magnets include kapellasite Cu3Zn(OH)6Cl2 and the spinel GeCo2O4. PMID- 29784923 TI - Author Correction: Long-term effects of mild traumatic brain injuries to oculomotor tracking performances and reaction times to simple environmental stimuli. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29784926 TI - Clinical utility of circulating non-coding RNAs - an update. AB - Over the past decade, the amount of research and the number of publications on associations between circulating small and long non-coding RNAs (ncRNAs) and cancer have grown exponentially. Particular focus has been placed on the development of diagnostic and prognostic biomarkers to enable efficient patient management - from early detection of cancer to monitoring for disease recurrence or progression after treatment. Owing to their high abundance and stability, circulating ncRNAs have potential utility as non-invasive, blood-based biomarkers that can provide information on tumour biology and the effects of treatments, such as targeted therapies and immunotherapies. Increasing evidence highlights the roles of ncRNAs in cell-to-cell communication, with a number of ncRNAs having the capacity to regulate gene expression outside of the cell of origin through extracellular vesicle-mediated transfer to recipient cells, with implications for cancer progression and therapy resistance. Moreover, 'foreign' microRNAs (miRNAs) encoded by non-human genomes (so-called xeno-miRNAs), such as viral miRNAs, have been shown to be present in human body fluids and can be used as biomarkers. Herein, we review the latest developments in the use of circulating ncRNAs as diagnostic and prognostic biomarkers and discuss their roles in cell-to-cell communication in the context of cancer. We provide a compendium of miRNAs and long ncRNAs that have been reported in the literature to be present in human body fluids and that have the potential to be used as diagnostic and prognostic cancer biomarkers. PMID- 29784924 TI - Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma. AB - Constant exposure to allergen triggers destructive type 2 cell-mediated inflammation. The effect of allergen specific immunotherapy (SIT) in maintaining airway epithelial barrier function in asthma remains unknown. In the current study, we showed that SIT maintained airway epithelial homeostasis in mice exposed to dermatophagoides farinae (Der f), which induced increased expression of IL-25, endoplasmic reticulum (ER) stress and airway epithelial apoptosis. Meanwhile, SIT treatment ameliorated airway inflammatory infiltration and hyper responsiveness in allergic mice. SIT treatment restored the airway epithelial integrity, attenuated Der f -induced airway epithelial ER stress and epithelial apoptosis. We also found that 4-PBA, an inhibitor of ER stress, suppressed airway epithelial ER stress and apoptosis in vitro. The pathological changes were partially induced by IL-25-induced ER stress, epithelial tight junction damage, and cell apoptosis in airways following allergen exposure. Furthermore, IL-25 induced ER stress in airway epithelial cells in vitro. The IL-25-induced airway epithelial apoptosis dependent on PERK activity was inhibited by 4-PBA. Taken together, we demonstrate that SIT is effective in allergic asthma and dependent on its depressive effect on the expression of IL-25, epithelial integrity damage, and epithelial ER stress. PMID- 29784927 TI - CTCs and benefit from radiotherapy. PMID- 29784925 TI - Acrylamide acute neurotoxicity in adult zebrafish. AB - Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited "depression-like" phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish. PMID- 29784929 TI - On-wafer fabrication of cavity mirrors for InGaN-based laser diode grown on Si. AB - Direct bandgap III-V semiconductor lasers grown on silicon (Si) are highly desired for monolithic integration with Si photonics. Fabrication of semiconductor lasers with a Fabry-Perot cavity usually includes facet cleavage, however, that is not compatible with on-chip photonic integration. Etching as an alternative approach holds a great advantage in preparing cavity mirrors with no need of breaking wafer into bars. However, gallium nitride (GaN) sidewalls prepared by dry etching often have a large roughness and etching damages, which would cause mirror loss due to optical scattering and carrier injection loss because of surface non-radiative recombination. A wet chemical polishing process of GaN sidewall facets formed by dry etching was studied in detail to remove the etching damages and smooth the vertical sidewalls. The wet chemical polishing technique combined with dry etching was successfully applied to the on-wafer fabrication of cavity mirrors, which enabled the realization of room temperature electrically injected InGaN-based laser diodes grown on Si. PMID- 29784928 TI - Statistical machine learning of sleep and physical activity phenotypes from sensor data in 96,220 UK Biobank participants. AB - Current public health guidelines on physical activity and sleep duration are limited by a reliance on subjective self-reported evidence. Using data from simple wrist-worn activity monitors, we developed a tailored machine learning model, using balanced random forests with Hidden Markov Models, to reliably detect a number of activity modes. We show that physical activity and sleep behaviours can be classified with 87% accuracy in 159,504 minutes of recorded free-living behaviours from 132 adults. These trained models can be used to infer fine resolution activity patterns at the population scale in 96,220 participants. For example, we find that men spend more time in both low- and high- intensity behaviours, while women spend more time in mixed behaviours. Walking time is highest in spring and sleep time lowest during the summer. This work opens the possibility of future public health guidelines informed by the health consequences associated with specific, objectively measured, physical activity and sleep behaviours. PMID- 29784930 TI - Comparative mRNA and miRNA expression in European mouflon (Ovis musimon) and sheep (Ovis aries) provides novel insights into the genetic mechanisms for female reproductive success. AB - Prolific breeds of domestic sheep (Ovis aries) are important genetic resources due to their reproductive performance, which is characterized by multiple lambs per birth and out-of-season breeding. However, the lack of a comprehensive understanding of the genetic mechanisms underlying the important reproductive traits, particularly from the evolutionary genomics perspective, has impeded the efficient advancement of sheep breeding. Here, for the first time, by performing RNA-sequencing we built a de novo transcriptome assembly of ovarian and endometrial tissues in European mouflon (Ovis musimon) and performed an mRNA miRNA integrated expression profiling analysis of the wild species and a highly prolific domestic sheep breed, the Finnsheep. We identified several novel genes with differentially expressed mRNAs (e.g., EREG, INHBA, SPP1, AMH, TDRD5, and ZP2) between the wild and domestic sheep, which are functionally involved in oocyte and follicle development and fertilization, and are significantly (adjusted P-value < 0.05) enriched in the Gene Ontology (GO) terms of various reproductive process, including the regulation of fertilization, oogenesis, ovarian follicle development, and sperm-egg recognition. Additionally, we characterized 58 differentially expressed miRNAs and 210 associated target genes that are essential for the regulation of female reproduction cycles through specific regulatory networks [e.g., (miR-136, miR-374a, miR-9-5p)-(EREG, INHBA)]. Furthermore, our integrated mRNA and miRNA expression profiling analysis elucidated novel direct and indirect miRNA/mRNA causal regulatory relationships related to the reproductive traits of the Ovis species. This study provides in depth insights into the genomic evolution underlying the reproductive traits of the Ovis species and valuable resources for ovine genomics. PMID- 29784932 TI - Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide. AB - Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery. To address this, we generated a library of ELPs ranging in size from 25 kDa to 110 kDa. Terminal plasma half-life was directly proportional to polymer size, and organ biodistribution was also size dependent. The kidneys accumulated the highest levels of ELP of all sizes, followed by the liver. Within the kidney, most ELP was found in the proximal tubule, but intra-renal localization shifted from exclusively cortical to a mixture of cortical and medullary as ELP size increased. PMID- 29784931 TI - Reconstruction of the diapsid ancestral genome permits chromosome evolution tracing in avian and non-avian dinosaurs. AB - Genomic organisation of extinct lineages can be inferred from extant chromosome level genome assemblies. Here, we apply bioinformatic and molecular cytogenetic approaches to determine the genomic structure of the diapsid common ancestor. We then infer the events that likely occurred along this lineage from theropod dinosaurs through to modern birds. Our results suggest that most elements of a typical 'avian-like' karyotype (40 chromosome pairs, including 30 microchromosomes) were in place before the divergence of turtles from birds ~255 mya. This genome organisation therefore predates the emergence of early dinosaurs and pterosaurs and the evolution of flight. Remaining largely unchanged interchromosomally through the dinosaur-theropod route that led to modern birds, intrachromosomal changes nonetheless reveal evolutionary breakpoint regions enriched for genes with ontology terms related to chromatin organisation and transcription. This genomic structure therefore appears highly stable yet contributes to a large degree of phenotypic diversity, as well as underpinning adaptive responses to major environmental disruptions via intrachromosomal repatterning. PMID- 29784933 TI - Well-protected quantum state transfer in a dissipative spin chain. AB - In this work, a mechanism is investigated for improving the quantum state transfer efficiency in a spin chain, which is in contact with a dissipative structured reservoir. The efficiency of the method is based on the addition of similar non-interacting auxiliary chains into the reservoir. In this way, we obtain the exact solution for the master equation of the spin chain in the presence of dissipation. It is found out that entering more auxiliary chains into the reservoir causes, in general, the better improvement of the fidelity of state transfer along the mentioned chain. Furthermore, it is reveal that the protocol has better efficiency for a chain with longer length. Therefore, by this method, quantum state transfer along a linear chain with an arbitrary number of qubits, can be well-protected against the dissipative noises. PMID- 29784934 TI - Investigation on the structures and magnetic properties of carbon or nitrogen doped cobalt ferrite nanoparticles. AB - Carbon or nitrogen doped cobalt ferrite nanoparticles were synthesized in the air by a facile calcination process. X-ray diffraction, mapping, X-ray photoelectron spectroscopy, and mossbauer spectra results indicate that the nonmetal elements as the interstitial one are doped into cobalt ferrite nanoparticles. The morphologies of doped cobalt ferrite nanoparticles change from near-spherical to irregular cubelike shapes gradually with the increased carbon or nitrogen concentration, and their particles sizes also increase more than 200 nm. Furthermore, the saturation magnetization of carbon doped cobalt ferrite is improved. Although the saturation magnetization of N-doped cobalt ferrite is not enhanced obviously due to the involved hematite, they also do not drop drastically. The results reveal an approach to synthesize large scale ferrite nanoparticles, and improve the magnetic properties of ferrite nanoparticles, and also provide the potential candidates to synthesis co-doped functional magnetic materials. PMID- 29784935 TI - A causal mechanism for childhood acute lymphoblastic leukaemia. AB - In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)-runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations. Risk is further modified by inherited genetics, chance and, probably, diet. Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. Childhood ALL may be a preventable cancer. PMID- 29784937 TI - An Oil-Free Picodrop Bioassay Platform for Synthetic Biology. AB - Droplet microfluidics enables massively-parallel analysis of single cells, biomolecules, and chemicals, making it valuable for high-throughput screens. However, many hydrophobic analytes are soluble in carrier oils, preventing their quantitative analysis with the method. We apply Printed Droplet Microfluidics to construct defined reactions with chemicals and cells incubated under air on an open array. The method interfaces with most bioanalytical tools and retains hydrophobic compounds in compartmentalized reactors, allowing their quantitation. PMID- 29784936 TI - Multiple convergent supergene evolution events in mating-type chromosomes. AB - Convergent adaptation provides unique insights into the predictability of evolution and ultimately into processes of biological diversification. Supergenes (beneficial gene linkage) are striking examples of adaptation, but little is known about their prevalence or evolution. A recent study on anther-smut fungi documented supergene formation by rearrangements linking two key mating-type loci, controlling pre- and post-mating compatibility. Here further high-quality genome assemblies reveal four additional independent cases of chromosomal rearrangements leading to regions of suppressed recombination linking these mating-type loci in closely related species. Such convergent transitions in genomic architecture of mating-type determination indicate strong selection favoring linkage of mating-type loci into cosegregating supergenes. We find independent evolutionary strata (stepwise recombination suppression) in several species, with extensive rearrangements, gene losses, and transposable element accumulation. We thus show remarkable convergence in mating-type chromosome evolution, recurrent supergene formation, and repeated evolution of similar phenotypes through different genomic changes. PMID- 29784939 TI - Automatic Cone Photoreceptor Localisation in Healthy and Stargardt Afflicted Retinas Using Deep Learning. AB - We present a robust deep learning framework for the automatic localisation of cone photoreceptor cells in Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) split-detection images. Monitoring cone photoreceptors with AOSLO imaging grants an excellent view into retinal structure and health, provides new perspectives into well known pathologies, and allows clinicians to monitor the effectiveness of experimental treatments. The MultiDimensional Recurrent Neural Network (MDRNN) approach developed in this paper is the first method capable of reliably and automatically identifying cones in both healthy retinas and retinas afflicted with Stargardt disease. Therefore, it represents a leap forward in the computational image processing of AOSLO images, and can provide clinical support in on-going longitudinal studies of disease progression and therapy. We validate our method using images from healthy subjects and subjects with the inherited retinal pathology Stargardt disease, which significantly alters image quality and cone density. We conduct a thorough comparison of our method with current state of-the-art methods, and demonstrate that the proposed approach is both more accurate and appreciably faster in localizing cones. As further validation to the method's robustness, we demonstrate it can be successfully applied to images of retinas with pathologies not present in the training data: achromatopsia, and retinitis pigmentosa. PMID- 29784940 TI - Starvation suppresses T cell appetite. PMID- 29784938 TI - Characterization of the rat cerebrospinal fluid proteome following acute cerebral ischemia using an aptamer-based proteomic technology. AB - The limited accessibility to the brain has turned the cerebrospinal fluid (CSF) into a valuable source that may contribute to the complete understanding of the stroke pathophysiology. Here we have described the CSF proteome in the hyper acute phase of cerebral ischemia by performing an aptamer-based proteomic assay (SOMAscan) in CSF samples collected before and 30 min after male Wistar rats had undergone a 90 min Middle Cerebral Artery Occlusion (MCAO) or sham-surgery. Proteomic results indicated that cerebral ischemia acutely increased the CSF levels of 716 proteins, mostly overrepresented in leukocyte chemotaxis and neuronal death processes. Seven promising candidates were further evaluated in rat plasma and brain (CKB, CaMK2A, CaMK2B, CaMK2D, PDXP, AREG, CMPK). The 3 CaMK2 family-members and CMPK early decreased in the infarcted brain area and, together with AREG, co-localized with neurons. Conversely, CKB levels remained consistent after the insult and specifically matched with astrocytes. Further exploration of these candidates in human plasma revealed the potential of CKB and CMPK to diagnose stroke, while CaMK2B and CMPK resulted feasible biomarkers of functional stroke outcome. Our findings provided insights into the CSF proteome following cerebral ischemia and identified new outstanding proteins that might be further considered as potential biomarkers of stroke. PMID- 29784941 TI - High-fidelity entanglement between a trapped ion and a telecom photon via quantum frequency conversion. AB - Entanglement between a stationary quantum system and a flying qubit is an essential ingredient of a quantum-repeater network. It has been demonstrated for trapped ions, trapped atoms, color centers in diamond, or quantum dots. These systems have transition wavelengths in the blue, red or near-infrared spectral regions, whereas long-range fiber-communication requires wavelengths in the low loss, low-dispersion telecom regime. A proven tool to interconnect flying qubits at visible/NIR wavelengths to the telecom bands is quantum frequency conversion. Here we use an efficient polarization-preserving frequency converter connecting 854 nm to the telecom O-band at 1310 nm to demonstrate entanglement between a trapped 40Ca+ ion and the polarization state of a telecom photon with a high fidelity of 98.2 +/- 0.2%. The unique combination of 99.75 +/- 0.18% process fidelity in the polarization-state conversion, 26.5% external frequency conversion efficiency and only 11.4 photons/s conversion-induced unconditional background makes the converter a powerful ion-telecom quantum interface. PMID- 29784943 TI - Thomson scattering in inhomogeneous plasmas: The Role of the Fluctuation Dissipation Theorem. AB - A self-consistent kinetic theory of Thomson scattering of an electromagnetic field by a non-uniform plasma is derived. We draw the readers' attention to the inconsistency in recent results on the Thomson scattering in inhomogeneous plasma, which leads to violation of the Fluctuation-Dissipation Theorem. We show, that not only the imaginary part, but also the derivatives of the real part of the dielectric susceptibility determine the amplitude and the width of the Thomson scattering spectral lines. As a result of inhomogeneity, these properties become asymmetric with respect to inversion of the sign of the frequency. A method is proposed for measuring local gradients of the electron density with the aid of Thomson scattering.Arising from: P. Kozlowski, et al. Sci. Rep. 6, 24283 (2016); https://doi.org/10.1038/srep24283 . PMID- 29784942 TI - Continuous addition of progenitors forms the cardiac ventricle in zebrafish. AB - The vertebrate heart develops from several progenitor lineages. After early differentiating first heart field (FHF) progenitors form the linear heart tube, late-differentiating second heart field (SHF) progenitors extend the atrium and ventricle, and form inflow and outflow tracts (IFT/OFT). However, the position and migration of late-differentiating progenitors during heart formation remains unclear. Here, we track zebrafish heart development using transgenics based on the cardiopharyngeal gene tbx1. Live imaging uncovers a tbx1 reporter-expressing cell sheath that continuously disseminates from the lateral plate mesoderm towards the forming heart tube. High-speed imaging and optogenetic lineage tracing corroborates that the zebrafish ventricle forms through continuous addition from the undifferentiated progenitor sheath followed by late-phase accrual of the bulbus arteriosus (BA). FGF inhibition during sheath migration reduces ventricle size and abolishes BA formation, refining the window of FGF action during OFT formation. Our findings consolidate previous end-point analyses and establish zebrafish ventricle formation as a continuous process. PMID- 29784944 TI - Value of urinary KIM-1 and NGAL combined with serum Cys C for predicting acute kidney injury secondary to decompensated cirrhosis. AB - Urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C (Cys C) are biomarkers of acute kidney injury (AKI). However, the efficacy of combining these indices to diagnose decompensated cirrhosis is unknown. This study involved 150 patients divided into AKI and non-AKI, and healthy individuals. Urinary KIM-1 and NGAL, serum Cys and creatine, and glomerular filtration rate (GFR) were compared based on Child-Pugh liver function class. Urinary KIM-1 and NGAL concentrations and serum Cys C levels were significantly higher in patients with AKI secondary to decompensated cirrhosis than in those with AKI not secondary to decompensated cirrhosis (p < 0.01). These were significantly associated with higher kidney injury index stages (p < 0.01) and negatively correlated with GFR in secondary AKI patients. Urinary KIM-1 and NGAL and serum Cys C increased significantly and GFR decreased as Child Pugh class of decompensated cirrhosis significantly increased (p < 0.05). SCr levels were significantly increased in Child-Pugh class C patients (p < 0.05). Urinary KIM-1, urinary NGAL, serum Cys C, and the combined detection factor, as screening indices, could aid in the early diagnosis of AKI secondary to decompensated cirrhosis. PMID- 29784945 TI - Author Correction: Enabling Controlling Complex Networks with Local Topological Information. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29784946 TI - Interpretable dimensionality reduction of single cell transcriptome data with deep generative models. AB - Single-cell RNA-sequencing has great potential to discover cell types, identify cell states, trace development lineages, and reconstruct the spatial organization of cells. However, dimension reduction to interpret structure in single-cell sequencing data remains a challenge. Existing algorithms are either not able to uncover the clustering structures in the data or lose global information such as groups of clusters that are close to each other. We present a robust statistical model, scvis, to capture and visualize the low-dimensional structures in single cell gene expression data. Simulation results demonstrate that low-dimensional representations learned by scvis preserve both the local and global neighbor structures in the data. In addition, scvis is robust to the number of data points and learns a probabilistic parametric mapping function to add new data points to an existing embedding. We then use scvis to analyze four single-cell RNA sequencing datasets, exemplifying interpretable two-dimensional representations of the high-dimensional single-cell RNA-sequencing data. PMID- 29784947 TI - A unified formulation of dichroic signals using the Borrmann effect and twisted photon beams. AB - Dichroic X-ray signals derived from the Borrmann effect and a twisted photon beam with topological charge l = 1 are formulated with an effective wavevector. The unification applies for non-magnetic and magnetic materials. Electronic degrees of freedom associated with an ion are encapsulated in multipoles previously used to interpret conventional dichroism and Bragg diffraction enhanced by an atomic resonance. A dichroic signal exploiting the Borrmann effect with a linearly polarized beam presents charge-like multipoles that include a hexadecapole. A difference between dichroic signals obtained with a twisted beam carrying spin polarization (circular polarization) and opposite winding numbers presents charge like atomic multipoles, whereas a twisted beam carrying linear polarization alone presents magnetic (time-odd) multipoles. Charge-like multipoles include a quadrupole, and magnetic multipoles include a dipole and an octupole. We discuss the practicalities and relative merits of spectroscopy exploiting the two remarkably closely-related processes. Signals using beams with topological charges l >= 2 present additional atomic multipoles. PMID- 29784948 TI - Simultaneous cell disruption and semi-quantitative activity assays for high throughput screening of thermostable L-asparaginases. AB - L-asparaginase, which catalyses the hydrolysis of L-asparagine to L-aspartate, has attracted the attention of researchers due to its expanded applications in medicine and the food industry. In this study, a novel thermostable L asparaginase from Pyrococcus yayanosii CH1 was cloned and over-expressed in Bacillus subtilis 168. To obtain thermostable L-asparaginase mutants with higher activity, a robust high-throughput screening process was developed specifically for thermophilic enzymes. In this process, cell disruption and enzyme activity assays are simultaneously performed in 96-deep well plates. By combining error prone PCR and screening, six brilliant positive variants and four key amino acid residue mutations were identified. Combined mutation of the four residues showed relatively high specific activity (3108 U/mg) that was 2.1 times greater than that of the wild-type enzyme. Fermentation with the mutant strain in a 5-L fermenter yielded L-asparaginase activity of 2168 U/mL. PMID- 29784949 TI - Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy. AB - Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA. PMID- 29784951 TI - Tomographic and multimodal scattering-type scanning near-field optical microscopy with peak force tapping mode. AB - Scattering-type scanning near-field optical microscopy (s-SNOM) enables nanoscale spectroscopic imaging and has been instrumental for many nano-photonic discoveries and in situ studies. However, conventional s-SNOM techniques with atomic force microscopy tapping mode operation and lock-in detections do not provide direct tomographic information with explicit tip-sample distance. Here, we present a non-traditional s-SNOM technique, named peak force scattering-type scanning near-field optical microscopy (PF-SNOM), by combination of peak force tapping mode and time-gated light detection. PF-SNOM enables direct sectioning of vertical near-field signals from a sample surface for both three-dimensional near field imaging and spectroscopic analysis. Tip-induced relaxation of surface phonon polaritons are revealed and modeled by considering tip damping. PF-SNOM also delivers a spatial resolution of 5 nm and can simultaneously measure mechanical and electrical properties together with optical near-field signals. PF SNOM is expected to facilitate three-dimensional nanoscale near-field characterizations and correlative in situ investigations on light-induced mechanical and electrical effects. PMID- 29784952 TI - Vanishing river ice cover in the lower part of the Danube basin - signs of a changing climate. AB - Many of the world's largest rivers in the extra tropics are covered with ice during the cold season, and in the Northern Hemisphere approximately 60% of the rivers experience significant seasonal effects of river ice. Here we present an observational data set of the ice cover regime for the lower part of the Danube River which spans over the period 1837-2016, and its the longest one on record over this area. The results in this study emphasize the strong impact of climate change on the occurrence of ice regime especially in the second part of the 20th century. The number of ice cover days has decreased considerably (~28days/century) mainly due to an increase in the winter mean temperature. In a long-term context, based on documentary evidences, we show that the ice cover occurrence rate was relatively small throughout the Medieval Warm Period (MWP), while the highest occurrence rates were found during the Maunder Minimum and Dalton Minimum periods. We conclude that the river ice regime can be used as a proxy for the winter temperature over the analyzed region and as an indicator of climate-change related impacts. PMID- 29784950 TI - Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma. AB - We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10-4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 * 10-12; rs1110446: OR = 1.79, P = 1.66 * 10-13; and rs3094137: OR = 1.73, P = 7.09 * 10-9). We then performed two field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A * 33:03 (OR = 1.97, P = 4.58 * 10-4) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A*33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region. PMID- 29784953 TI - Reply to 'Thomson scattering in inhomogeneous plasmas: The Role of the Fluctuation-Dissipation Theorem'. AB - In a comment on our article "Theory of Thomson scattering in inhomogeneous media", V. V. Belyi asserts that there is an inconsistency in our method of applying gradient effects via the dielectric superposition principle, in violation of the fluctuation-dissipation theorem; and that his Klimontovich Langevin formulation would be more appropriate to our application. While we agree that a generalization, along the lines of Belyi's work, would be required for strongly coupled systems, for the weakly coupled systems which we considered, these corrections are not necessary and our approach is still appropriate.Replying to: V. Belyi, Sci. Rep. 8 (2018); https://doi.org/10.1038/s41598-018-25319-6 . PMID- 29784954 TI - The structural basis of nanobody unfolding reversibility and thermoresistance. AB - Nanobodies represent the variable binding domain of camelid heavy-chain antibodies and are employed in a rapidly growing range of applications in biotechnology and biomedicine. Their success is based on unique properties including their reported ability to reversibly refold after heat-induced denaturation. This view, however, is contrasted by studies which involve irreversibly aggregating nanobodies, asking for a quantitative analysis that clearly defines nanobody thermoresistance and reveals the determinants of unfolding reversibility and aggregation propensity. By characterizing nearly 70 nanobodies, we show that irreversible aggregation does occur upon heat denaturation for the large majority of binders, potentially affecting application relevant parameters like stability and immunogenicity. However, by deriving aggregation propensities from apparent melting temperatures, we show that an optional disulfide bond suppresses nanobody aggregation. This effect is further enhanced by increasing the length of a complementarity determining loop which, although expected to destabilize, contributes to nanobody stability. The effect of such variations depends on environmental conditions, however. Nanobodies with two disulfide bonds, for example, are prone to lose their functionality in the cytosol. Our study suggests strategies to engineer nanobodies that exhibit optimal performance parameters and gives insights into general mechanisms which evolved to prevent protein aggregation. PMID- 29784955 TI - Integration of large-scale data for extraction of integrated Arabidopsis root cell-type specific models. AB - Plant organs consist of multiple cell types that do not operate in isolation, but communicate with each other to maintain proper functions. Here, we extract models specific to three developmental stages of eight root cell types or tissue layers in Arabidopsis thaliana based on a state-of-the-art constraint-based modeling approach with all publicly available transcriptomics and metabolomics data from this system to date. We integrate these models into a multi-cell root model which we investigate with respect to network structure, distribution of fluxes, and concordance to transcriptomics and proteomics data. From a methodological point, we show that the coupling of tissue-specific models in a multi-tissue model yields a higher specificity of the interconnected models with respect to network structure and flux distributions. We use the extracted models to predict and investigate the flux of the growth hormone indole-3-actetate and its antagonist, trans-Zeatin, through the root. While some of predictions are in line with experimental evidence, constraints other than those coming from the metabolic level may be necessary to replicate the flow of indole-3-actetate from other simulation studies. Therefore, our work provides the means for data-driven multi tissue metabolic model extraction of other Arabidopsis organs in the constraint based modeling framework. PMID- 29784956 TI - Dynamics and function of DNA methylation in plants. AB - DNA methylation is a conserved epigenetic modification that is important for gene regulation and genome stability. Aberrant patterns of DNA methylation can lead to plant developmental abnormalities. A specific DNA methylation state is an outcome of dynamic regulation by de novo methylation, maintenance of methylation and active demethylation, which are catalysed by various enzymes that are targeted by distinct regulatory pathways. In this Review, we discuss DNA methylation in plants, including methylating and demethylating enzymes and regulatory factors, and the coordination of methylation and demethylation activities by a so-called methylstat mechanism; the functions of DNA methylation in regulating transposon silencing, gene expression and chromosome interactions; the roles of DNA methylation in plant development; and the involvement of DNA methylation in plant responses to biotic and abiotic stress conditions. PMID- 29784957 TI - Metabolic Reprogramming in Leaf Lettuce Grown Under Different Light Quality and Intensity Conditions Using Narrow-Band LEDs. AB - Light-emitting diodes (LEDs) are an artificial light source used in closed-type plant factories and provide a promising solution for a year-round supply of green leafy vegetables, such as lettuce (Lactuca sativa L.). Obtaining high-quality seedlings using controlled irradiation from LEDs is critical, as the seedling health affects the growth and yield of leaf lettuce after transplantation. Because key molecular pathways underlying plant responses to a specific light quality and intensity remain poorly characterised, we used a multi-omics-based approach to evaluate the metabolic and transcriptional reprogramming of leaf lettuce seedlings grown under narrow-band LED lighting. Four types of monochromatic LEDs (one blue, two green and one red) and white fluorescent light (control) were used at low and high intensities (100 and 300 MUmol.m-2.s-1, respectively). Multi-platform mass spectrometry-based metabolomics and RNA-Seq were used to determine changes in the metabolome and transcriptome of lettuce plants in response to different light qualities and intensities. Metabolic pathway analysis revealed distinct regulatory mechanisms involved in flavonoid and phenylpropanoid biosynthetic pathways under blue and green wavelengths. Taken together, these data suggest that the energy transmitted by green light is effective in creating a balance between biomass production and the production of secondary metabolites involved in plant defence. PMID- 29784960 TI - Some like it hot - sex determination in turtles. PMID- 29784958 TI - Polycomb Repressive Complex 2 attenuates the very high expression of the Arabidopsis gene NRT2.1. AB - PRC2 is a major regulator of gene expression in eukaryotes. It catalyzes the repressive chromatin mark H3K27me3, which leads to very low expression of target genes. NRT2.1, which encodes a key root nitrate transporter in Arabidopsis, is targeted by H3K27me3, but the function of PRC2 on NRT2.1 remains unclear. Here, we demonstrate that PRC2 directly targets and down-regulates NRT2.1, but in a context of very high transcription, in nutritional conditions where this gene is one of the most highly expressed genes in the transcriptome. Indeed, the mutation of CLF, which encodes a PRC2 subunit, leads to a loss of H3K27me3 at NRT2.1 and results, exclusively under permissive conditions for NRT2.1, in a further increase in NRT2.1 expression, and specifically in tissues where NRT2.1 is normally expressed. Therefore, our data indicates that PRC2 tempers the hyperactivity of NRT2.1 in a context of very strong transcription. This reveals an original function of PRC2 in the control of the expression of a highly expressed gene in Arabidopsis. PMID- 29784959 TI - Commercially Available Natural Benzyl Esters and Their Synthetic Analogs Exhibit Different Toxicities against Insect Pests. AB - Benzyl methyl ester, also known as methyl benzoate (MB), is a volatile organic compound that exists naturally as a floral fragrance in many plants. Our behavioral bioassays show that MB and some of its naturally occurring and synthetic analogs kill insects at different life stages. Compared to commercial pesticides containing pyriproxyfen and acetamiprid, MB and some analogs are 1.3 to 3.4 times more toxic to gypsy moth larvae and brown marmorated stinkbug nymphs. The arthropod repellent DEET is also a benzyl ester, and shares the same chemical skeleton with MB. They differ by the diethylamide ester and a methyl group on the benzene ring in DEET. However, unlike MB, DEET does not kill insects; instead, it deters or repels them. Exactly how DEET causes the repellent effect in target organisms is still a mystery. Due to the MB's structural similarity to DEET, exploring the structure - activity relationship (SAR) of the MB analogs will provide useful information for the discovery of the mode and mechanistic actions of DEET as an insect repellent. In addition, the SAR will allow researchers to modify the chemical structure of the MB molecule, leading to the development of more efficient, safe, and environmentally - friendly green pesticides. PMID- 29784962 TI - Carrier thermometry of cold ytterbium atoms in an optical lattice clock. AB - The ultracold atomic gas serving as the quantum reference is a key part of an optical lattice clock, and the temperature of atoms in the optical lattice affects the uncertainty and instability of the optical lattice clocks. Since the carrier spectrum of the clock transition in the lattices reflects the thermal dynamics of cold atoms, the temperature of atoms can be extracted from the carrier spectrum in a non-magic wavelength lattice of ytterbium optical clocks. Furthermore, the temperatures obtained from the carrier spectra are in good agreement with the results obtained by the time-of-flight method and thermometry based on the sideband spectrum. In addition, the heating effects caused by the lattice laser are studied on the basis of the sample temperatures. PMID- 29784963 TI - Single entity resolution valving of nanoscopic species in liquids. AB - Investigating biological and synthetic nanoscopic species in liquids, at the ultimate resolution of single entity, is important in diverse fields1-5. Progress has been made6-10, but significant barriers need to be overcome such as the need for intense fields, the lack of versatility in operating conditions and the limited functionality in solutions of high ionic strength for biological applications. Here, we demonstrate switchable electrokinetic nanovalving able to confine and guide single nano-objects, including macromolecules, with sizes down to around 10 nanometres, in a lab-on-chip environment. The nanovalves are based on spatiotemporal tailoring of the potential energy landscape of nano-objects using an electric field, modulated collaboratively by wall nanotopography and by embedded electrodes in a nanochannel system. We combine nanovalves to isolate single entities from an ensemble, and demonstrate their guiding, confining, releasing and sorting. We show on-demand motion control of single immunoglobulin G molecules, quantum dots, adenoviruses, lipid vesicles, dielectric and metallic particles, suspended in electrolytes with a broad range of ionic strengths, up to biological levels. Such systems can enable nanofluidic, large-scale integration and individual handling of multiple entities in applications ranging from single species characterization and screening to in situ chemical or biochemical synthesis in continuous on-chip processes. PMID- 29784964 TI - High-speed photothermal off-resonance atomic force microscopy reveals assembly routes of centriolar scaffold protein SAS-6. AB - The self-assembly of protein complexes is at the core of many fundamental biological processes1, ranging from the polymerization of cytoskeletal elements, such as microtubules2, to viral capsid formation and organelle assembly3. To reach a comprehensive understanding of the underlying mechanisms of self assembly, high spatial and temporal resolutions must be attained. This is complicated by the need to not interfere with the reaction during the measurement. As self-assemblies are often governed by weak interactions, they are especially difficult to monitor with high-speed atomic force microscopy (HS-AFM) due to the non-negligible tip-sample interaction forces involved in current methods. We have developed a HS-AFM technique, photothermal off-resonance tapping (PORT), which is gentle enough to monitor self-assembly reactions driven by weak interactions. We apply PORT to dissect the self-assembly reaction of SAS-6 proteins, which form a nine-fold radially symmetric ring-containing structure that seeds the formation of the centriole organelle. Our analysis reveals the kinetics of SAS-6 ring formation and demonstrates that distinct biogenesis routes can be followed to assemble a nine-fold symmetrical structure. PMID- 29784961 TI - Sarcodon imbricatus polysaccharides improve mouse hematopoietic function after cyclophosphamide-induced damage via G-CSF mediated JAK2/STAT3 pathway. AB - Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines. After 28 days of treatment, SIPS enhanced the bodyweight and thymus indices of the mice, alleviated enlargement of the spleen and liver, and contributed to the recovery of peripheral blood to normal levels. More importantly, the percentages of B lymphocytes and hematopoietic stem cells or hematopoietic progenitor cells were significantly elevated in bone marrow. Based on an antibody chip analysis and enzyme-linked immunosorbent assay, SIPS were found to successfully regulate 12 cytokines to healthy levels in serum and spleen. The cytokines included the following: interleukins 1Ra, 2, 3, 4, 5, and 6, tumor necrosis factor alpha, interferon-gamma, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), C-C motif chemokine1, and monocyte chemoattractant protein-1. Moreover, SIPS upregulated the phosphorylation levels of janus kinase 2 (JAK2) and the signal transducer and activator of transcription 3 (STAT3) in the spleen, and similar results were validated in CHRF cells, K562 cells, and BMMNCs. The data indicate that SIPS activated the JAK2/STAT3 pathway, possibly by interactions among multiple cytokines, particularly G-CSF. We found that SIPS was remarkably beneficial to the bone marrow hematopoietic system, and we anticipate that it could improve myelosuppression induced by long-term radiotherapy or chemotherapy. PMID- 29784965 TI - Broadband, electrically tunable third-harmonic generation in graphene. AB - Optical harmonic generation occurs when high intensity light (>1010 W m-2) interacts with a nonlinear material. Electrical control of the nonlinear optical response enables applications such as gate-tunable switches and frequency converters. Graphene displays exceptionally strong light-matter interaction and electrically and broadband tunable third-order nonlinear susceptibility. Here, we show that the third-harmonic generation efficiency in graphene can be increased by almost two orders of magnitude by controlling the Fermi energy and the incident photon energy. This enhancement is due to logarithmic resonances in the imaginary part of the nonlinear conductivity arising from resonant multiphoton transitions. Thanks to the linear dispersion of the massless Dirac fermions, gate controllable third-harmonic enhancement can be achieved over an ultrabroad bandwidth, paving the way for electrically tunable broadband frequency converters for applications in optical communications and signal processing. PMID- 29784966 TI - Author Correction: Ultrahard carbon film from epitaxial two-layer graphene. AB - In the version of this Article originally published, the second affiliation for Walter A. de Heer had not been included; it should be 'TICNN, Tianjin University, Tianjin, China'. This has now been added and the numbering of subsequent affiliations amended accordingly in all versions of the Article. PMID- 29784967 TI - The Cardiometabolic Burden of Self-Perceived Obesity: A Multilevel Analysis of a Nationally Representative Sample of Korean Adults. AB - Emerging evidence has shown that self-perception of overweight/obese status is associated with unfavorable cardiometabolic outcomes, above and beyond actual body weight. Given the lack of research among Asian populations, we examined the association between weight perception and metabolic syndrome (MetS) and cardiometabolic risks among Koreans. Data from the 2010-2015 Korea National Health and Nutrition Examination Survey, including women (N = 12,181) and men (N = 9,448) aged 19-65 years, were analyzed. Weight status perception was measured by participants' self-evaluation of their body size ("very/slightly obese," "normal," and "very/slightly thin"). Overall, 23.2% of women and 28.7% of men had MetS. Our cross-sectional multilevel logistic analyses showed a significant positive association between self-perceived obesity (vs. perceived normal weight) and MetS, independent of BMI and sociodemographic/behavioral/medical conditions, with a stronger association detected among men (OR = 1.38, p < 0.05) than women (OR = 1.22, p < 0.05), confirmed by a statistically significant interaction. Additionally, perceived obesity was associated with high blood pressure (OR = 1.27, p < 0.05) and high triglycerides (OR = 1.38, p < 0.05) among men and low high-density lipoprotein cholesterol (OR = 1.15, p < 0.05) among women. While further prospective research is needed, our findings suggest that perception of being obese may be an unfavorable indicator of cardiometabolic health among Koreans regardless of actual body weight. PMID- 29784968 TI - Ultranarrow-bandwidth filter based on a thermal EIT medium. AB - We present high-contrast electromagnetically-induced-transparency (EIT) spectra in a heated vapor cell of single isotope 87Rb atoms. The EIT spectrum has both high resonant transmission up to 67% and narrow linewidth of 1.1 MHz. We get rid of the possible amplification resulted from the effects of amplification without population inversion and four-wave mixing. Therefore, this high transmitted light is not artificial. The theoretical prediction of the probe transmission agrees well with the data and the experimental parameters can be derived reasonably from the model. Such narrow and high-contrast spectral profile can be employed as a high precision bandpass filter, which provides a significant advantage in terms of stability and tunability. The central frequency tuning range of the filter is larger than 100 MHz with out-of-band blocking >=15 dB. This bandpass filter can effectively produce light fields with subnatural linewidth. Nonlinearity associating with the narrow-linewidth and high-contrast EIT profile can be very useful in the applications utilizing the EIT effect. PMID- 29784969 TI - North American domestic pigs are susceptible to experimental infection with Japanese encephalitis virus. AB - Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is capable of causing encephalitic diseases in children. While humans can succumb to severe disease, the transmission cycle is maintained by viremic birds and pigs in endemic regions. Although JEV is regarded as a significant threat to the United States (U.S.), the susceptibility of domestic swine to JEV infection has not been evaluated. In this study, domestic pigs from North America were intravenously challenged with JEV to characterize the pathological outcomes. Systemic infection followed by the development of neutralizing antibodies were observed in all challenged animals. While most clinical signs were limited to nonspecific symptoms, virus dissemination and neuroinvasion was observed at the acute phase of infection. Detection of infectious viruses in nasal secretions suggest infected animals are likely to promote the vector-free transmission of JEV. Viral RNA present in tonsils at 28 days post infection demonstrates the likelihood of persistent infection. In summary, our findings indicate that domestic pigs can potentially become amplification hosts in the event of an introduction of JEV into the U.S. Vector-free transmission to immunologically naive vertebrate hosts is also likely through nasal shedding of infectious viruses. PMID- 29784970 TI - Association of Blood Pressure with Fasting Blood Glucose Levels in Northeast China: A Cross-Sectional Study. AB - Hypertension and diabetes mellitus (DM) have become major public health issues, and previous studies have shown that there is an association between hypertension and DM. However, there is a lack of detailed information about this association. This study aimed to explore how different blood pressure (BP) levels were associated with fasting blood glucose (FBG) levels. A cross-sectional survey with adults aged 18 to 79 years was conducted in Jilin Province, China in 2012. Lambda mu-sigma (LMS) was used to preliminarily explore the associations of BP with FBG. Quantile regression (QR) was performed to identify the specific associations by adjusting for confounding factors. The distributions of systolic blood pressure (SBP) (chi2 = 710.76, P < 0.001) and diastolic blood pressure (DBP) (chi2 = 460.20, P < 0.001) were different according to gender. LMS showed that the associations of BP with FBG became stronger when the FBG levels were close to 5.6 mmol/L. QR showed that FBG was positively associated with SBP (P30 to P90) and DBP (P20 to P90) in males. In females, FBG was positively associated with SBP from only P85 to P90. In summary, FBG was positively associated with BP in a gender-dependent manner. PMID- 29784971 TI - Normalized spatial complexity analysis of neural signals. AB - The spatial complexity of neural signals, which was traditionally quantified by omega complexity, varies inversely with the global functional connectivity level across distinct region-of-interests, thus provides a novel approach in functional connectivity analysis. However, the measures in omega complexity are sensitive to the number of neural time-series. Here, normalized spatial complexity was suggested to overcome the above limitation, and was verified by the functional near-infrared spectroscopy (fNIRS) data from a previous published autism spectrum disorder (ASD) research. By this new method, several conclusions consistent with traditional approaches on the pathological mechanisms of ASD were found, i.e., the prefrontal cortex made a major contribution to the hypo-connectivity of young children with ASD. Moreover, some novel findings were also detected (e.g., significantly higher normalized regional spatial complexities of bilateral prefrontal cortices and the variability of normalized local complexity differential of right temporal lobe, and the regional differences of measures in normalized regional spatial complexity), which could not be successfully detected via traditional approaches. These results confirmed the value of this novel approach, and extended the methodology system of functional connectivity. This novel technique could be applied to the neural signal of other neuroimaging techniques and other neurological and cognitive conditions. PMID- 29784972 TI - Comprehensive analysis of the mouse cytochrome P450 family responsible for omega 3 epoxidation of eicosapentaenoic acid. AB - Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selected and identified to confer omega-3 epoxidation of EPA to yield 17,18-epoxyeicosatetraenoic acid (17,18-EpETE). Stereoselective production of 17,18-EpETE by each CYP isoform was confirmed, and molecular modeling indicated that chiral differences stem from different EPA binding conformations in the catalytic domains of respective CYP enzymes. PMID- 29784974 TI - Longing for HIV protection. PMID- 29784976 TI - Microbial metabolic gatekeeping in the jejunum. PMID- 29784973 TI - Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment. AB - Prohibitin (PHB) was originally isolated and characterized as an anti proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues. Furthermore, studies verified that PHB1 and PHB2 are involved in the biological processes of tumorigenesis, including cancer cell proliferation, apoptosis, and metastasis. Two small molecule inhibitors, Rocaglamide (RocA) and fluorizoline, derived from medicinal plants, were demonstrated to interact directly with PHB1 and thus inhibit the interaction of PHB with Raf-1, impeding Raf-1/ERK signaling cascades and significantly suppressing cancer cell metastasis. In addition, a short peptide ERAP and a natural product xanthohumol were shown to target PHB2 directly and prohibit cancer progression in estrogen-dependent cancers. As more efficient biomarkers and targets are urgently needed for cancer diagnosis and treatment, here we summarize the functional role of prohibitin domain family proteins, focusing on PHB1 and PHB2 in tumorigenesis and cancer development, with the expectation that targeting the prohibitin domain family will offer more clues for cancer therapy. PMID- 29784975 TI - A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel. AB - Type IV secretion systems (T4SSs) are complex machines used by bacteria to deliver protein and DNA complexes into target host cells1-5. Conserved ATPases are essential for T4SS function, but how they coordinate their activities to promote substrate transfer remains poorly understood. Here, we show that the DotB ATPase associates with the Dot-Icm T4SS at the Legionella cell pole through interactions with the DotO ATPase. The structure of the Dot-Icm apparatus was solved in situ by cryo-electron tomography at 3.5 nm resolution and the cytoplasmic complex was solved at 3.0 nm resolution. These structures revealed a cell envelope-spanning channel that connects to the cytoplasmic complex. Further analysis revealed a hexameric assembly of DotO dimers associated with the inner membrane complex, and a DotB hexamer associated with the base of this cytoplasmic complex. The assembly of a DotB-DotO energy complex creates a cytoplasmic channel that directs the translocation of substrates through the T4SS. These data define distinct stages in Dot-Icm machine biogenesis, advance our understanding of channel activation, and identify an envelope-spanning T4SS channel. PMID- 29784977 TI - Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide. AB - Bacterial quorum sensing is a well-characterized communication system that governs a large variety of collective behaviours. By comparison, quorum sensing regulation in eukaryotic microbes remains poorly understood, especially its functional role in eukaryote-specific behaviours, such as sexual reproduction. Cryptococcus neoformans is a prevalent fungal pathogen that has two defined sexual cycles (bisexual and unisexual) and is a model organism for studying sexual reproduction in fungi. Here, we show that the quorum sensing peptide Qsp1 serves as an important signalling molecule for both forms of sexual reproduction. Qsp1 orchestrates various differentiation and molecular processes, including meiosis, the hallmark of sexual reproduction. It activates bisexual mating, at least in part through the control of pheromone, a signal necessary for bisexual activation. Notably, Qsp1 also plays a major role in the intercellular regulation of unisexual initiation and coordination, in which pheromone is not strictly required. Through a multi-layered genetic screening approach, we identified the atypical zinc finger regulator Cqs2 as an important component of the Qsp1 signalling cascade during both bisexual and unisexual reproduction. The absence of Cqs2 eliminates the Qsp1-stimulated mating response. Together, these findings extend the range of behaviours governed by quorum sensing to sexual development and meiosis. PMID- 29784979 TI - Pervasive introgression facilitated domestication and adaptation in the Bos species complex. AB - Species of the Bos genus, including taurine cattle, zebu, gayal, gaur, banteng, yak, wisent and bison, have been domesticated at least four times and have been an important source of meat, milk and power for many human cultures. We sequence the genomes of gayal, gaur, banteng, wisent and bison, and provide population genomic sequencing of an additional 98 individuals. We use these data to determine the phylogeny and evolutionary history of these species and show that the threatened gayal is an independent species or subspecies. We show that there has been pronounced introgression among different members of this genus, and that it in many cases has involved genes of considerable adaptive importance. For example, genes under domestication selection in cattle (for example, MITF) were introgressed from domestic cattle to yak. Also, genes in the response-to-hypoxia pathway (for example, EGLN1, EGLN2 and HIF3a) have been introgressed from yak to Tibetan cattle, probably facilitating their adaptation to high altitude. We also validate that there is an association between the introgressed EGLN1 allele and haemoglobin and red blood cell concentration. Our results illustrate the importance of introgression as a source of adaptive variation and during domestication, and suggest that the Bos genus evolves as a complex of genetically interconnected species with shared evolutionary trajectories. PMID- 29784978 TI - Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria. AB - Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite Plasmodium praefalciparum. Little is known about the other gorilla- and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum, but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers, as well as convergent evolution, were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor, shows a host-specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans. PMID- 29784980 TI - Global mismatch of policy and research on drivers of biodiversity loss. AB - The United Nations 2030 Agenda for Sustainable Development calls for urgent actions to reduce global biodiversity loss. Here, we synthesize >44,000 articles published in the past decade to assess the research focus on global drivers of loss. Relative research efforts on different drivers are not well aligned with their assessed impact, and multiple driver interactions are hardly considered. Research on drivers of biodiversity loss needs urgent realignment to match predicted severity and inform policy goals. PMID- 29784981 TI - Human activities might influence oncogenic processes in wild animal populations. AB - Based on the abundant studies available on humans showing clear associations between rapid environmental changes and the rate of neoplasia, we propose that human activities might increase cancer rate in wild populations through numerous processes. Most of the research on this topic has concentrated on wildlife cancer prevalence in environments that are heavily contaminated with anthropogenic chemicals. Here, we propose that human activities might also increase cancer rate in wild populations through additional processes including light pollution, accidental (for example, human waste) or intentional (for example, bird feeders) wildlife feeding (and the associated change of diet), or reduction of genetic diversity in human-impacted habitats. The human species can thus be defined as an oncogenic species, moderating the environment in the way that it causes cancer in other wild populations. As human impacts on wildlife are predicted to increase rather than decrease (for example, in the context of urbanization), acknowledging the possible links between human activity and cancer in wild populations is crucial. PMID- 29784982 TI - The palaeoecological context of the Oldowan-Acheulean in southern Africa. AB - The influence of climatic and environmental change on human evolution in the Pleistocene epoch is understood largely from extensive East African stable isotope records. These records show increasing proportions of C4 plants in the Early Pleistocene. We know far less about the expansion of C4 grasses at higher latitudes, which were also occupied by early Homo but are more marginal for C4 plants. Here we show that both C3 and C4 grasses and prolonged wetlands remained major components of Early Pleistocene environments in the central interior of southern Africa, based on enamel stable carbon and oxygen isotope data and associated faunal abundance and phytolith evidence from the site of Wonderwerk Cave. Vegetation contexts associated with Oldowan and early Acheulean lithic industries, in which climate is driven by an interplay of regional rainfall seasonality together with global CO2 levels, develop along a regional distinct trajectory compared to eastern South Africa and East Africa. PMID- 29784983 TI - Thermodynamic and crystallographic model for anion uptake by hydrated calcium aluminate (AFm): an example of molybdenum. AB - Amongst all cement phases, hydrated calcium aluminate (AFm) plays a major role in the retention of anionic species. Molybdenum (Mo), whose 93Mo isotope is considered a major steel activation product, will be released mainly under the form of MoO42- in a radioactive waste repository. Understanding its fate is of primary importance in a safety analysis of such disposal. This necessitates models that can both predict quantitatively the sorption of Mo by AFm and determine the nature of the sorption process (i.e., reversible adsorption or incorporation). This study investigated the Cl-/MoO42- exchange processes occurring in an AFm initially containing interlayer Cl in alkaline conditions using flow-through experiments. The evolution of the solid phase was characterized using an electron probe microanalyzer and synchrotron high-energy X ray scattering. All data, together with their quantitative modeling, coherently indicated that Mo replaced Cl in the AFm interlayer. The structure of the interlayer is described with unprecedented atomic-scale detail based on a combination of real- and reciprocal-space analyses of total X-ray scattering data. In addition, modeling of several independent chemical experiments elucidated that Cl-/OH- exchange processes occur together with Cl-/MoO42- exchange. This competitive effect must be considered when determining the Cl /MoO42- selectivity constant. PMID- 29784984 TI - Author Correction: Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan. AB - The originally published version of this Article contained an error in the spelling of the author Nathaniel W. Oswald, which was incorrectly given as Nathaniel W. Olswald. This has now been corrected in both the PDF and HTML versions of the Article. PMID- 29784987 TI - Communicating catalysts. PMID- 29784985 TI - Chronic rhinosinusitis with nasal polyps is characterized by dysbacteriosis of the nasal microbiota. AB - Chronic rhinosinusitis with nasal polyp (CRSwNP) patients are often characterized by asthma comorbidity and a type-2 inflammation of the sinonasal mucosa. The mucosal microbiota has been suggested to be implicated in the persistence of inflammation, but associations have not been well defined. To compare the bacterial communities of healthy subjects with CRSwNP patients, we collected nasal swabs from 17 healthy subjects, 21 CRSwNP patients without asthma (CRSwNP A), and 20 CRSwNP patients with co-morbid asthma (CRSwNP+A). We analysed the microbiota using high-throughput sequencing of the bacterial 16S rRNA. Bacterial communities were different between the three groups. Haemophilus influenzae was significantly enriched in CRSwNP patients, Propionibacterium acnes in the healthy group; Staphylococcus aureus was abundant in the CRSwNP-A group, even though present in 57% of patients. Escherichia coli was found in high amounts in CRSwNP+A patients. Nasal tissues of CRSwNP+A patients expressed significantly higher concentrations of IgE, SE-IgE, and IL-5 compared to those of CRSwNP-A patients. Co-cultivation demonstrated that P. acnes growth was inhibited by H. influenzae, E. coli and S. aureus. The nasal microbiota of healthy subjects are different from those of CRSwNP-A and CRSwNP+A patients. However, the most abundant species in healthy status could not inhibit those in CRSwNP disease. PMID- 29784986 TI - A workflow for the integrative transcriptomic description of molecular pathology and the suggestion of normalizing compounds, exemplified by Parkinson's disease. AB - The volume of molecular observations on human diseases in public databases is continuously increasing at accelerating rates. A bottleneck is their computational integration into a coherent description, from which researchers may derive new well-founded hypotheses. Also, the need to integrate data from different technologies (genetics, coding and regulatory RNA, proteomics) emerged in order to identify biomarkers for early diagnosis and prognosis of complex diseases and therefore facilitating the development of novel treatment approaches. We propose here a workflow for the integrative transcriptomic description of the molecular pathology in Parkinsons's Disease (PD), including suggestions of compounds normalizing disease-induced transcriptional changes as a paradigmatic example. We integrated gene expression profiles, miRNA signatures, and publicly available regulatory databases to specify a partial model of the molecular pathophysiology of PD. Six genetic driver elements (2 genes and 4 miRNAs) and several functional network modules that are associated with PD were identified. Functional modules were assessed for their statistical significance, cellular functional homogeneity, literature evidence, and normalizing small molecules. In summary, our workflow for the joint regulatory analysis of coding and non-coding RNA, has the potential to yield clinically as well as biologically relevant information, as demonstrated here on PD data. PMID- 29784988 TI - Tritium trinkets. PMID- 29784989 TI - Vibrations that live long and prosper. PMID- 29784990 TI - Hitting the sweet spot. PMID- 29784991 TI - A new fundamental type of conformational isomerism. AB - Isomerism is a fundamental chemical concept, reflecting the fact that the arrangement of atoms in a molecular entity has a profound influence on its chemical and physical properties. Here we describe a previously unclassified fundamental form of conformational isomerism through four resolved stereoisomers of a transoid (BF)O(BF)-quinoxalinoporphyrin. These comprise two pairs of enantiomers that manifest structural relationships not describable within existing IUPAC nomenclature and terminology. They undergo thermal diastereomeric interconversion over a barrier of 104 +/- 2 kJ mol-1, which we term 'akamptisomerization'. Feasible interconversion processes between conceivable synthesis products and reaction intermediates were mapped out by density functional theory calculations, identifying bond-angle inversion (BAI) at a singly bonded atom as the reaction mechanism. We also introduce the necessary BAI stereodescriptors parvo and amplo. Based on an extended polytope formalism of molecular structure and stereoisomerization, BAI-driven akamptisomerization is shown to be the final fundamental type of conformational isomerization. PMID- 29784992 TI - Dependences of microstructure on electromagnetic interference shielding properties of nano-layered Ti3AlC2 ceramics. AB - The microstructure dependent electromagnetic interference (EMI) shielding properties of nano-layered Ti3AlC2 ceramics were presented in this study by comparing the shielding properties of various Ti3AlC2 ceramics with distinct microstructures. Results indicate that Ti3AlC2 ceramics with dense microstructure and coarse grains are more favourable for superior EMI shielding efficiency. High EMI shielding effectiveness over 40 dB at the whole Ku-band frequency range was achieved in Ti3AlC2 ceramics by microstructure optimization, and the high shielding effectiveness were well maintained up to 600 degrees C. A further investigation reveals that only the absorption loss displays variations upon modifying microstructure by allowing more extensive multiple reflections in coarse layered grains. Moreover, the absorption loss of Ti3AlC2 was found to be much higher than those of highly conductive TiC ceramics without layered structure. These results demonstrate that nano-layered MAX phase ceramics are promising candidates of high-temperature structural EMI shielding materials and provide insightful suggestions for achieving high EMI shielding efficiency in other ceramic-based shielding materials. PMID- 29784993 TI - Author Correction: Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29784995 TI - An autonomously electrically self-healing liquid metal-elastomer composite for robust soft-matter robotics and electronics. AB - Large-area stretchable electronics are critical for progress in wearable computing, soft robotics and inflatable structures. Recent efforts have focused on engineering electronics from soft materials-elastomers, polyelectrolyte gels and liquid metal. While these materials enable elastic compliance and deformability, they are vulnerable to tearing, puncture and other mechanical damage modes that cause electrical failure. Here, we introduce a material architecture for soft and highly deformable circuit interconnects that are electromechanically stable under typical loading conditions, while exhibiting uncompromising resilience to mechanical damage. The material is composed of liquid metal droplets suspended in a soft elastomer; when damaged, the droplets rupture to form new connections with neighbours and re-route electrical signals without interruption. Since self-healing occurs spontaneously, these materials do not require manual repair or external heat. We demonstrate this unprecedented electronic robustness in a self-repairing digital counter and self-healing soft robotic quadruped that continue to function after significant damage. PMID- 29784994 TI - Designing natural and synthetic immune tissues. AB - Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed-in cell culture and animal models-and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function. In this Review, we discuss recent interdisciplinary strategies that are merging materials science and immunology to create engineered immune tissues in vitro and in vivo. We also highlight the hurdles facing these approaches and the need for comparison to existing clinical options, relevant animal models, and other emerging technologies. PMID- 29784997 TI - Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells. AB - Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo. In this hPS-cell-based neuroectoderm patterning model, two tissue-scale morphogenetic signals-cell shape and cytoskeletal contractile force-instruct neuroepithelial/neural plate border patterning via BMP-SMAD signalling. We further show that ectopic mechanical activation and exogenous BMP signalling modulation are sufficient to perturb neuroepithelial/neural plate border patterning. This study provides a useful microengineered, hPS-cell-based model with which to understand the biomechanical principles that guide neuroectoderm patterning and hence to study neural development and disease. PMID- 29784996 TI - Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke. AB - Stroke is the primary cause of disability due to the brain's limited ability to regenerate damaged tissue. After stroke, an increased inflammatory and immune response coupled with severely limited angiogenesis and neuronal growth results in a stroke cavity devoid of normal brain tissue. In the adult, therapeutic angiogenic materials have been used to repair ischaemic tissues through the formation of vascular networks. However, whether a therapeutic angiogenic material can regenerate brain tissue and promote neural repair is poorly understood. Here we show that the delivery of an engineered immune-modulating angiogenic biomaterial directly to the stroke cavity promotes tissue formation de novo, and results in axonal networks along thee generated blood vessels. This regenerated tissue produces functional recovery through the established axonal networks. Thus, this biomaterials approach generates a vascularized network of regenerated functional neuronal connections within previously dead tissue and lays the groundwork for the use of angiogenic materials to repair other neurologically diseased tissues. PMID- 29784998 TI - Polarization insensitive frequency conversion for an atom-photon entanglement distribution via a telecom network. AB - Long-lifetime quantum storages accessible to the telecom photonic infrastructure are essential to long-distance quantum communication. Atomic quantum storages have achieved subsecond storage time corresponding to 1000 km transmission time for a telecom photon through a quantum repeater algorithm. However, the telecom photon cannot be directly interfaced to typical atomic storages. Solid-state quantum frequency conversions fill this wavelength gap. Here we report on the experimental demonstration of a polarization-insensitive solid-state quantum frequency conversion to a telecom photon from a short-wavelength photon entangled with an atomic ensemble. Atom-photon entanglement has been generated with a Rb atomic ensemble and the photon has been translated to telecom range while retaining the entanglement by our nonlinear-crystal-based frequency converter in a Sagnac interferometer. PMID- 29784999 TI - Publisher Correction: Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29785000 TI - Publisher Correction: Aerodynamic generation of electric fields in turbulence laden with charged inertial particles. AB - The original version of this Article contained an error in the last sentence of the second paragraph of the 'Atmospheric rarefaction effects' section of the Results, which incorrectly read 'The other one emulates the rarefied, CO2-rich Martian atmosphere (MU? = 1.3 * 10-5 N s m-2) at 6.9 mbar and 210 K, which gives rho? = 1.6 * 10-12 kg m-3.' The correct version states 'rho? = 1.6 * 10-2 kg m-3' in place of 'rho? = 1.6 * 10-12 kg m-3'. This has been corrected in both the PDF and HTML versions of the Article. PMID- 29785001 TI - Evaluation of weed control efficacy and crop safety of the new HPPD-inhibiting herbicide-QYR301. AB - QYR301, 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid 4-[2-chloro-3-(3,5-dimethyl pyrazol-1-ylmethyl)-4-methanesulfonyl-benzoyl]-2,5-dimethyl-2H-pyrazol-3-yl ester, is a novel HPPD-inhibiting herbicide and was evaluated to provide a reference for post-emergence (POST) application under greenhouse and field conditions. The crop safety (180 and 360 g active ingredient (a.i.) ha-1 treatments) experiment revealed that wheat, paddy, garlic and corn were the only four crops without injury at both examined herbicide rates. The weed control efficacy (60 and 120 g a.i. ha-1) experiment showed that QYR301 exhibited high efficacy against many weeds, especially weeds infesting paddy fields. Furthermore, it is interesting that both susceptible and multiple herbicide resistant Echinochloa crus-galli (L.) Beauv. and Echinochloa phyllopogon (Stapf) Koss, two notorious weed species in paddy field, remained susceptible to QYR301. Further crop tolerance results indicated that 20 tested paddy hybrids displayed different levels of tolerance to QYR301, with the japonica paddy hybrids having more tolerance than indica paddy hybrids under greenhouse conditions. Results obtained from field experiments showed that QYR301 POST at 135 to 180 g a.i. ha-1 was recommended to provide satisfactory full-season control of E. crus-galli and Leptochloa chinensis (L.) Nees and to maximize rice yields. These findings indicate that QYR301 possesses great potential for the management of weeds in paddy fields. PMID- 29785002 TI - Using Single Molecule mRNA Fluorescent in Situ Hybridization (RNA-FISH) to Quantify mRNAs in Individual Murine Oocytes and Embryos. AB - Changes in abundance of mRNAs during oocyte growth and maturation and during pre implantation embryo development have been documented using quantitative real-time RT-PCR (qPCR), microarray analyses, and whole genome sequencing. However, these techniques require amplification of mRNAs, normalization using housekeeping genes, can be biased for abundant transcripts, and/or require large numbers of oocytes and embryos which can be difficult to acquire from mammalian species. We optimized a single molecule RNA fluorescence in situ hybridization (RNA-FISH) protocol, which amplifies fluorescence signal to detect candidate transcripts, for use with individual oocytes and embryos. Quantification using the software Localize showed patterns of Gdf9 and Pou5f1 mRNA expression in oocytes and embryos that were consistent with previously published data. Interestingly, low levels of Nanog mRNA were also accurately and reproducibly measured in oocytes and one- and two-cell embryos suggesting that RNA-FISH could be used to detect and quantify low abundance transcripts. Unlike other techniques, RNA-FISH is also able to detect changes in the localization patterns of mRNAs which may be used to monitor post-transcriptional regulation of a transcript. Thus, RNA-FISH represents an important technique to investigate potential mechanisms associated with the synthesis and stability of candidate mRNAs in mammalian oocytes and embryos. PMID- 29785003 TI - Publisher Correction: The gut-liver axis and the intersection with the microbiome. AB - In the original version of Table 1 published online, upward arrows to indicate increased translocation of PAMPs were missing from the row entitled 'Translocation' for both the column on alcoholic liver disease and nonalcoholic fatty liver disease. This error has now been updated in the PDF and HTML version of the article. PMID- 29785005 TI - Nanopore sequencing technology: a new route for the fast detection of unauthorized GMO. AB - In order to strengthen the current genetically modified organism (GMO) detection system for unauthorized GMO, we have recently developed a new workflow based on DNA walking to amplify unknown sequences surrounding a known DNA region. This DNA walking is performed on transgenic elements, commonly found in GMO, that were earlier detected by real-time PCR (qPCR) screening. Previously, we have demonstrated the ability of this approach to detect unauthorized GMO via the identification of unique transgene flanking regions and the unnatural associations of elements from the transgenic cassette. In the present study, we investigate the feasibility to integrate the described workflow with the MinION Next-Generation-Sequencing (NGS). The MinION sequencing platform can provide long read-lengths and deal with heterogenic DNA libraries, allowing for rapid and efficient delivery of sequences of interest. In addition, the ability of this NGS platform to characterize unauthorized and unknown GMO without any a priori knowledge has been assessed. PMID- 29785004 TI - A direct tissue-grafting approach to increasing endogenous brown fat. AB - There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled "exBAT", we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism. PMID- 29785006 TI - The era of immunogenomics/immunopharmacogenomics. AB - Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments. However, the molecular mechanisms by which these new therapies kill tumor cells are still not fully understood. In this regard, we have begun to explore the role of newly developed tools such as next-generation sequencing in the genetic characterization of both cancer cells and host immune cells, a field that is called immunogenomics/ immunopharmacogenomics. This new field has enormous potential to help us better understand changes in our immune system during the course of various disease conditions. Here we report the potential of deep sequencing of T-cell and B-cell receptors in capturing the molecular contribution of the immune system, which we believe plays critical roles in the pathogenesis of various human diseases. PMID- 29785008 TI - Massively Parallel Coincidence Counting of High-Dimensional Entangled States. AB - Entangled states of light are essential for quantum technologies and fundamental tests of physics. Current systems rely on entanglement in 2D degrees of freedom, e.g., polarization states. Increasing the dimensionality provides exponential speed-up of quantum computation, enhances the channel capacity and security of quantum communication protocols, and enables quantum imaging; unfortunately, characterizing high-dimensional entanglement of even bipartite quantum states remains prohibitively time-consuming. Here, we develop and experimentally demonstrate a new theory of camera detection that leverages the massive parallelization inherent in an array of pixels. We show that a megapixel array, for example, can measure a joint Hilbert space of 1012 dimensions, with a speed up of nearly four orders-of-magnitude over traditional methods. The technique uses standard geometry with existing technology, thus removing barriers of entry to quantum imaging experiments, generalizes readily to arbitrary numbers of entangled photons, and opens previously inaccessible regimes of high-dimensional quantum optics. PMID- 29785007 TI - Characterization and prevalence of two novel CHEK2 large deletions in Greek breast cancer patients. AB - Germline CHEK2 mutations confer increased cancer risk, for breast and other types, which is variable depending on the specific mutation. Of these, Large Genomic Rearrangements (LGRs) have been rarely reported; to date only eight LGRs have been published with just the Czech founder mutation, the deletion of exons 9 and 10, being molecularly characterized and studied extensively. The present study aimed to molecularly define and determine the contribution of two rare, apparently novel CHEK2 LGRs, among Greek breast cancer patients. These specifically involve a ~6 kb in-frame deletion of exons 2 & 3 that removes CHEK2's FHA domain and a ~7.5 kb in-frame deletion of exon 6, which removes an alpha-helix of CHEK2's kinase domain. The latter was identified in 5 out of 2355 (0.22%) patients tested, while haplotype analysis revealed a common disease associated haplotype, suggesting a single common ancestor and a Greek founder. Although in-frame, this LGR is predicted to be damaging by a yeast-based functional assay and structure-function predictions. The present study highlights the existence of rare, population-specific, genomic events in a known breast cancer predisposing gene, which can explain a proportion of hereditary breast cancer. Identification of such mutation carriers is rather important since appropriate clinical actionability will be inferred. PMID- 29785009 TI - Physical activity, sleep, and fatigue in community dwelling Stroke Survivors. AB - Stroke can lead to physiological and psychological impairments and impact individuals' physical activity (PA), fatigue and sleep patterns. We analysed wrist-worn accelerometry data and the Fatigue Assessment Scale from 41 stroke survivors following a physical rehabilitation programme, to examine relationships between PA levels, fatigue and sleep. Validated acceleration thresholds were used to quantify time spent in each PA intensity/sleep category. Stroke survivors performed less moderate to vigorous PA (MVPA) in 10 minute bouts than the National Stroke guidelines recommend. Regression analysis revealed associations at baseline between light PA and fatigue (p = 0.02) and MVPA and sleep efficiency (p = 0.04). Light PA was positively associated with fatigue at 6 months (p = 0.03), whilst sleep efficiency and fatigue were associated at 9 months (p = 0.02). No other effects were shown at baseline, 6 or 9 months. The magnitude of these associations were small and are unlikely to be clinically meaningful. Larger trials need to examine the efficacy and utility of accelerometry to assess PA and sleep in stroke survivors. PMID- 29785011 TI - A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases. AB - Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg = 0.75, P = 6.84 * 10-62). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases. PMID- 29785013 TI - Genetic identification of brain cell types underlying schizophrenia. AB - With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. By applying knowledge of the cellular taxonomy of the brain from single-cell RNA sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common-variant genomic results consistently mapped to pyramidal cells, medium spiny neurons (MSNs) and certain interneurons, but far less consistently to embryonic, progenitor or glial cells. These enrichments were due to sets of genes that were specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (genes involved in synaptic function, those encoding mRNAs that interact with FMRP, antipsychotic targets, etc.) generally implicated the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with MSNs did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia. PMID- 29785012 TI - Multiplex assessment of protein variant abundance by massively parallel sequencing. AB - Determining the pathogenicity of genetic variants is a critical challenge, and functional assessment is often the only option. Experimentally characterizing millions of possible missense variants in thousands of clinically important genes requires generalizable, scalable assays. We describe variant abundance by massively parallel sequencing (VAMP-seq), which measures the effects of thousands of missense variants of a protein on intracellular abundance simultaneously. We apply VAMP-seq to quantify the abundance of 7,801 single-amino-acid variants of PTEN and TPMT, proteins in which functional variants are clinically actionable. We identify 1,138 PTEN and 777 TPMT variants that result in low protein abundance, and may be pathogenic or alter drug metabolism, respectively. We observe selection for low-abundance PTEN variants in cancer, and show that p.Pro38Ser, which accounts for ~10% of PTEN missense variants in melanoma, functions via a dominant-negative mechanism. Finally, we demonstrate that VAMP seq is applicable to other genes, highlighting its generalizability. PMID- 29785014 TI - 3' UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk. AB - Widespread mRNA 3' UTR shortening through alternative polyadenylation 1 promotes tumor growth in vivo 2 . A prevailing hypothesis is that it induces proto oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3'UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3' UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3' UTR shortening, including PTEN, a crucial tumor suppressor gene 3 involved in ceRNA crosstalk 4 with nine 3'UTR-shortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3' UTR-shortening regulator 2 , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3' UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis. PMID- 29785010 TI - Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. AB - Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk. PMID- 29785016 TI - Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases. AB - Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors. PMID- 29785017 TI - MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas. AB - High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p < 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma. PMID- 29785015 TI - Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam. AB - To examine the transmission dynamics of Mycobacterium tuberculosis (Mtb) isolated from tuberculosis patients in Ho Chi Minh City, Vietnam, we sequenced the whole genomes of 1,635 isolates and compared these with 3,144 isolates from elsewhere. The data identify an underlying burden of disease caused by the endemic Mtb lineage 1 associated with the activation of long-term latent infection, and a threefold higher burden associated with the more recently introduced Beijing lineage and lineage 4 Mtb strains. We find that Beijing lineage Mtb is frequently transferred between Vietnam and other countries, and detect higher levels of transmission of Beijing lineage strains within this host population than the endemic lineage 1 Mtb. Screening for parallel evolution of Beijing lineage associated SNPs in other Mtb lineages as a signal of positive selection, we identify an alteration in the ESX-5 type VII-secreted protein EsxW, which could potentially contribute to the enhanced transmission of Beijing lineage Mtb in Vietnamese and other host populations. PMID- 29785018 TI - Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma. AB - Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for alpha-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P < 0.001). Univariate and multivariate analyses showed that adenocarcinomas with the fetal-type component had a significantly lower overall survival rate than the other histological subtypes, except for the micropapillary predominant subtype. Our study demonstrated that adenocarcinomas with the fetal type component had a poor prognosis that was comparable to that of micropapillary adenocarcinoma. The presence of the high-grade fetal adenocarcinoma component in lung adenocarcinomas is an important prognostic marker. PMID- 29785019 TI - Cribriform-morular variant of thyroid carcinoma: a neoplasm with distinctive phenotype associated with the activation of the WNT/beta-catenin pathway. AB - Cribriform-morular variant of thyroid carcinoma is classically associated with familial adenomatous polyposis but, it can also occur as a sporadic neoplasm. This neoplasm is much more frequently observed in women than in men (ratio of 61:1). In familial adenomatous polyposis patients, tumors are generally multifocal and/or bilateral (multinodular appearance), whereas in the sporadic cases tumors tend to occur as single nodules. The tumors are well delimited, and characteristically show a blending of follicular, cribriform, papillary, trabecular, solid, and morular patterns. Neoplastic cells are tall or cuboidal with the occasional nuclear features of classic papillary thyroid carcinoma. The morules include cells with peculiar nuclear clearing and show positivity for CDX2 and CD10. Angioinvasion and capsular invasion have been described in about 30 and 40% of cases, respectively, with lymph node metastases in less than 10% of patients and distant metastases in 6%. Although this tumor has good prognosis, neuroendocrine and/or poor differentiation have been associated with aggressive behavior. Tumor cells can be focally positive or negative for thyroglobulin, but are always positive for TTF-1, estrogen and progesterone receptors, and negative for calcitonin and cytokeratin 20. Nuclear and cytoplasmic staining for beta catenin is the hallmark of this tumor type; this feature plays a role in fine needle aspiration biopsy. Cribriform-morular variant of thyroid carcinoma has a peculiar endodermal (intestinal-like) type phenotype, activation of the WNT/beta catenin signaling pathway, and belongs to the non-BRAF-non-RAS subtype of the molecular classification of thyroid tumors. Elevated expression of estrogen and progesterone receptors and activation of the WNT/beta-catenin pathway may prove useful as putative therapeutic targets in cases that do not respond to conventional therapy. Clinicians should be alerted to the possibility of familial adenomatous polyposis when a diagnosis of cribriform-morular variant of thyroid carcinoma is made. Instead of being considered as a variant of papillary thyroid carcinoma its designation as cribriform-morular thyroid carcinoma seems more appropriate. PMID- 29785020 TI - Glypican-1 immunohistochemistry does not separate mesothelioma from pulmonary adenocarcinoma. AB - Immunohistochemistry (IHC) is used to help differentiate pleural mesothelioma from pulmonary adenocarcinoma in pleural biopsies and cytology specimens of pleural effusions due to overlapping morphologic features between these two malignancies. The aim of this study is to evaluate IHC glypican-1, a recently proposed marker for epithelioid mesothelioma, in our cohort of mesotheliomas and pulmonary adenocarcinoma. Tissue microarrays with duplicate cores from 33 cases of mesotheliomas (28 epithelioid type and five sarcomatoid type) and 21 cases of pulmonary adenocarcinoma were stained with glypican-1 antibody. The proportion of cases by tumor type showing staining with glypican-1 and the H-score for each tumor type were evaluated. All 33 cases of mesothelioma and all 20 cases of pulmonary adenocarcinoma with interpretable cores showed positive cytoplasmic staining. All but one case of mesothelioma and all pulmonary adenocarcinomas showed staining in at least 80% of the tumor cells. The mean H-score for glypican 1 of mesothelioma (134 +/- 59, mean +/- SD) was not significantly different from that for pulmonary adenocarcinoma (156 +/- 60; P = 0.21). Neither epithelioid type (mean H-score 135 +/- 57) nor sarcomatoid type (mean H-score 130 +/- 78) of mesothelioma showed different H-scores when compared to pulmonary adenocarcinoma (P = 0.23 and 0.42, respectively). In conclusion, glypican-1 IHC does not differentiate mesothelioma from pulmonary adenocarcinoma. PMID- 29785021 TI - Advanced septa size quantitation determines the evaluation of histological fibrosis outcome in chronic hepatitis B patients. AB - Hepatitis B (HBV)-related fibrosis can be reversed after effective antiviral therapy. However, detailed changes of collagen characteristics during fibrosis regression remain unclear. Paired biopsy samples obtained from chronic hepatitis B patients were imaged with second harmonic generation/two photon excitation fluorescence (SHG/TPEF)-based microscopy to identify and quantify collagen features in portal, septal, and fibrillar areas. According to the changes of Ishak stage and qFibrosis score, a total of 117 patients with paired liver biopsy appeared to have four different outcomes after 78-week antiviral therapy: fast reverse (9%), reverse (63%), stable (15%), or progress (13%) on fibrosis. Among 71 collagen features identified by SHG/TPEF analysis, the most prominent fibrosis reversion occurred in the "septal" area, followed by the "fibrillar" area, but not in the "portal" area (P < 0.001). Further analysis of 1060 individual septa identified four parameters that correlated with fibrosis reversion: average width, maximum width, number of fibers, and number of cross-link fibers (P < 0.001). Average septal width was independently associated with regressive septa (odds ratio (OR) = 5.22, 95% confidence interval (CI): 4.17-6.53; P < 0.001), with an AUROC of 0.96 (95% CI: 0.95-0.97). The threshold used to discriminate reversal of fibrosis was 30 MUm. In conclusion, septal collagen was determined to be the most useful histological feature for evaluation of dynamic changes in liver fibrosis. Septal width was the most predictive indicator of prognosis in liver fibrosis. PMID- 29785022 TI - Novel peptide GX1 inhibits angiogenesis by specifically binding to transglutaminase-2 in the tumorous endothelial cells of gastric cancer. AB - The clinical application of GX1, an optimal gastric cancer (GC) targeting peptide, is greatly limited because its receptor in the GC vasculature is unknown. In this study, we screened the candidate receptor of GX1, transglutaminase-2(TGM2), by co-immunoprecipitation (co-IP) combined with mass spectrometry. We found that TGM2 was up-regulated in GC vascular endothelial cells and that GX1 receptor expression was suppressed correspondingly after TGM2 downregulation. A highly consistent co-localization of GX1 receptor and TGM2 was detected at both the cellular and tissue levels. High TGM2 expression was evident in GC tissues from patients with poor prognosis. After TGM2 downregulation, the GX1-mediated inhibition of proliferation and migration and the induction of the apoptosis of GC vascular endothelial cells were weakened or even reversed. Finally, we observed that GX1 could inhibit the GTP-binding activity of TGM2 by reducing its intracellular distribution and downregulating its downstream molecular targets (nuclear factor-kappa B, NF-kappaB; hypoxia-inducible factor 1 alpha, HIF1alpha) in GC vascular endothelial cells. Our study confirms that peptide GX1 can inhibit angiogenesis by directly binding to TGM2, subsequently reducing the GTP-binding activity of TGM2 and thereby suppressing its downstream pathway(NF-kappaB/HIF1alpha). Our conclusions suggest that GX1/TGM2 may provide a new target for the diagnosis and treatment of GC. PMID- 29785023 TI - HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition. AB - Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16- monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition. PMID- 29785024 TI - Targeting skeletal endothelium to ameliorate bone loss. AB - Recent studies have identified a specialized subset of CD31hiendomucinhi (CD31hiEMCNhi) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31hiEMCNhi endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31hiEMCNhi endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of Slit3 reduced skeletal CD31hiEMCNhi endothelium, resulted in low bone mass because of impaired bone formation and partially reversed the high bone mass phenotype of Shn3-/- mice. This coupling between osteoblasts and CD31hiEMCNhi endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss. PMID- 29785025 TI - An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling. AB - Beige adipocytes have recently been shown to regulate energy dissipation when activated and help organisms defend against hypothermia and obesity. Prior reports indicate that beige-like adipocytes exist in adult humans and that they may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we found that expression of the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) was induced in subcutaneous fat during the activation of these cells and that acetylcholine-producing immune cells within this tissue regulated this signaling pathway via paracrine mechanisms. CHRNA2 functioned selectively in uncoupling protein 1 (Ucp1)-positive beige adipocytes, increasing thermogenesis through a cAMP- and protein kinase A-dependent pathway. Furthermore, this signaling via CHRNA2 was conserved and present in human subcutaneous adipocytes. Inactivation of Chrna2 in mice compromised the cold-induced thermogenic response selectively in subcutaneous fat and exacerbated high-fat diet-induced obesity and associated metabolic disorders, indicating that even partial loss of beige fat regulation in vivo had detrimental consequences. Our results reveal a beige selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors in energy metabolism. These findings may lead to identification of therapeutic targets to counteract human obesity. PMID- 29785027 TI - Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome. AB - Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases. Xlr3b binds to dendritic mRNAs, and its overexpression inhibits dendritic transport of the mRNA encoding CaMKII-alpha, promoting synaptic dysfunction. Notably, treatment with 5-ALA, which is converted into G-quadruplex-binding metabolites, reduces RNA polymerase II recruitment and represses Xlr3b transcription in ATR-X model mice. 5-ALA treatment also rescues decreased synaptic plasticity and cognitive deficits seen in ATR-X model mice. Our findings suggest a potential therapeutic strategy to target G-quadruplexes and decrease cognitive impairment associated with ATR-X syndrome. PMID- 29785026 TI - Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. AB - The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1. Cancer associated mutations in the sequence encoding the MLL3 PHD repeats disrupt the interaction between MLL3 and BAP1 and correlate with poor patient survival. Cancer cells that had PHD-associated MLL3 mutations or lacked BAP1 showed reduced recruitment of MLL3 and the H3K27 demethylase KDM6A (also known as UTX) to gene enhancers. As a result, inhibition of the H3K27 methyltransferase activity of the Polycomb repressive complex 2 (PRC2) in tumor cells harboring BAP1 or MLL3 mutations restored normal gene expression patterns and impaired cell proliferation in vivo. This study provides mechanistic insight into the oncogenic effects of PHD-associated mutations in MLL3 and suggests that restoration of a balanced state of Polycomb-COMPASS activity may have therapeutic efficacy in tumors that bear mutations in the genes encoding these epigenetic factors. PMID- 29785029 TI - Highly Bactericidal Macroporous Antimicrobial Polymeric Gel for Point-of-Use Water Disinfection. AB - Access to clean and safe water supply remains inadequate in many developing countries. One of the key challenges is to remove pathogenic bacteria from the water supply via effective water disinfection technologies to prevent the spread of diseases and to ensure the safety of consumers. Herein, a highly effective point-of-use (on-demand) water disinfection technology, in the form of a polymeric scaffold called macroporous antimicrobial polymeric gel (MAPG), is demonstrated. MAPG is easy to fabricate, completely organic and possess inherent antimicrobial property which makes it non-reliant on inorganic compounds such as silver where the long-term toxicity remains unknown. MAPG is highly bactericidal and can disinfect bacteria-contaminated water (ca. 108 CFU mL-1) at a capacity of about >50 times the mass of the organic material used, inactivating >99% of both Gram-negative and Gram-positive bacteria including Escherichia coli, Vibrio cholerae and Staphylococcus aureus within 20 minutes of treatment. When fabricated in a syringe, MAPG eliminates E. coli from contaminated water source by >8.0 log10 reduction in bacteria counts (i.e., no viable bacteria were detected after treatment), and the syringe can be reused multiple times without losing potency. The MAPG technology is not only restricted to water disinfection but may also be applicable in other bacteria inactivation applications. PMID- 29785028 TI - The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease. PMID- 29785030 TI - Landau-Zener-Stuckelberg Interferometry for Majorana Qubit. AB - Stimulated by a recent experiment observing successfully two superconducting states with even- and odd-number of electrons in a nanowire topological superconductor as expected from the existence of two end Majorana quasiparticles (MQs) [Albrecht et al., Nature 531, 206 (2016)], we propose a way to manipulate Majorana qubit exploiting quantum tunneling effects. The prototype setup consists of two one-dimensional (1D) topological superconductors coupled by a tunneling junction which can be controlled by gate voltage. We show that the time evolution of superconducting phase difference at the junction under a voltage bias induces an oscillation in energy levels of the Majorana parity states, whereas the level crossing is avoided by a small coupling energy of MQs in the individual 1D superconductors. This results in a Landau-Zener-Stuckelberg (LZS) interference between the Majorana parity states. Adjusting pulses of bias voltage and gate voltage, one can construct a LZS interferometry which provides an arbitrary manipulation of the Majorana qubit. PMID- 29785031 TI - Nanoparticle-templated nanofiltration membranes for ultrahigh performance desalination. AB - Nanofiltration (NF) membranes with ultrahigh permeance and high rejection are highly beneficial for efficient desalination and wastewater treatment. Improving water permeance while maintaining the high rejection of state-of-the-art thin film composite (TFC) NF membranes remains a great challenge. Herein, we report the fabrication of a TFC NF membrane with a crumpled polyamide (PA) layer via interfacial polymerization on a single-walled carbon nanotubes/polyether sulfone composite support loaded with nanoparticles as a sacrificial templating material, using metal-organic framework nanoparticles (ZIF-8) as an example. The nanoparticles, which can be removed by water dissolution after interfacial polymerization, facilitate the formation of a rough PA active layer with crumpled nanostructure. The NF membrane obtained thereby exhibits high permeance up to 53.5 l m-2h-1 bar-1 with a rejection above 95% for Na2SO4, yielding an overall desalination performance superior to state-of-the-art NF membranes reported so far. Our work provides a simple avenue to fabricate advanced PA NF membranes with outstanding performance. PMID- 29785032 TI - Solvents can control solute molecular identity. AB - For solution-phase chemical reactions, the solvent is often considered simply as a medium to allow the reactants to encounter each other by diffusion. Although examples of direct solvent effects on molecular solutes exist, such as the compression of solute bonding electrons due to Pauli repulsion interactions, the solvent is not usually considered a part of the chemical species of interest. We show, using quantum simulations of Na2, that when there are local specific interactions between a solute and solvent that are energetically on the same order as a hydrogen bond, the solvent controls not only the bond dynamics but also the chemical identity of the solute. In tetrahydrofuran, dative bonding interactions between the solvent and Na atoms lead to unique coordination states that must cross a free energy barrier of ~8 kBT-undergoing a chemical reaction-to interconvert. Each coordination state has its own dynamics and spectroscopic signatures, highlighting the importance of considering the solvent in the identity of condensed-phase chemical systems. PMID- 29785033 TI - Identification and characterization of diverse coherences in the Fenna-Matthews Olson complex. AB - The idea that excitonic (electronic) coherences are of fundamental importance to natural photosynthesis gained popularity when slowly dephasing quantum beats (QBs) were observed in the two-dimensional electronic spectra of the Fenna Matthews-Olson (FMO) complex at 77 K. These were assigned to superpositions of excitonic states, a controversial interpretation, as the strong chromophore environment interactions in the complex suggest fast dephasing. Although it has been pointed out that vibrational motion produces similar spectral signatures, a concrete assignment of these oscillatory signals to distinct physical processes is still lacking. Here we revisit the coherence dynamics of the FMO complex using polarization-controlled two-dimensional electronic spectroscopy, supported by theoretical modelling. We show that the long-lived QBs are exclusively vibrational in origin, whereas the dephasing of the electronic coherences is completed within 240 fs even at 77 K. We further find that specific vibrational coherences are produced via vibronically coupled excited states. The presence of such states suggests that vibronic coupling is relevant for photosynthetic energy transfer. PMID- 29785034 TI - Trophic overlap between expanding and contracting fish predators in a range margin undergoing change. AB - Climate change is predicted to cause a freshening of the Baltic Sea, facilitating range expansions of freshwater species and contractions of marine. Resident marine flounders (Platichthys flesus) and expansive freshwater roach (Rutilus rutilus) are dominant consumers in the Baltic Sea sublittoral where they occur in partial sympatry. By comparing patterns of resource use by flounders and roach along a declining resource gradient of blue mussels (Mytilus trossulus) our aim was to explore predator functional responses and the degree of trophic overlap. Understanding the nature of density-dependent prey acquisition has important implications for predicting population dynamics of both predators and their shared prey. Results showed a highly specialized diet for both species, high reliance on blue mussels throughout the range, similar prey size preference and high trophic overlap. Highest overlap occurred where blue mussels were abundant but overlap was also high where they were scarce. Our results highlight the importance of a single food item - the blue mussel - for both species, likely promoting high population size and range expansion of roach. Findings also suggest that range expansion of roach may have a top-down structuring force on mussels that differ in severity and location from that originating from resident flounders. PMID- 29785035 TI - Optimized delivery of siRNA into 3D tumor spheroid cultures in situ. AB - 3D tissue culture provides a physiologically relevant and genetically tractable system for studying normal and malignant human tissues. Despite this, gene silencing studies using siRNA has proved difficult. In this study, we have identified a cause for why traditional siRNA transfection techniques are ineffective in eliciting gene silencing in situ within 3D cultures and proposed a simple method for significantly enhancing siRNA entry into spheroids/organoids. In 2D cell culture, the efficiency of gene silencing is significantly reduced when siRNA complexes are prepared in the presence of serum. Surprisingly, in both 3D tumour spheroids and primary murine organoids, the presence of serum during siRNA preparation rapidly promotes entry and internalization of Cy3-labelled siRNA in under 2 hours. Conversely, siRNA prepared in traditional low-serum transfection media fails to gain matrigel or spheroid/organoid entry. Direct measurement of CTNNB1 mRNA (encoding beta-catenin) from transfected tumour spheroids confirmed a transient but significant knockdown of beta-catenin when siRNA:liposome complexes were formed with serum, but not when prepared in the presence of reduced-serum media (Opti-MEM). Our studies suggest a simple modification to standard lipid-based transfection protocols facilitates rapid siRNA entry and transient gene repression, providing a platform for researchers to improve siRNA efficiency in established 3D cultures. PMID- 29785036 TI - A novel microRNA signature predicts survival in liver hepatocellular carcinoma after hepatectomy. AB - Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer. In the current study, genome-wide miRNA-Seq and mRNA profiles in 318 LIHC patients derived from The Cancer Genome Atlas (TCGA) were analysed to identify miRNA-based signatures for LIHC prognosis with survival analysis and a semi supervised principal components (SPC) method. A seven-miRNA signature was confirmed for overall survival (OS) prediction by comparing miRNA profiles in paired primary tumour and solid tumour normal tissues. Thereafter, a linear prognostic model that consisted of seven miRNAs was established and used to divide patients into high- and low-risk groups according to prognostic scores. Subsequent Kaplan-Meier analysis revealed that the seven-miRNA signature correlated with a good predictive clinical outcome for 5-year survival in LIHC patients. Additionally, this miRNA-based prognostic model could also be used for OS prognosis of LIHC patients in early stages, which could guide the future therapy of those patients and promote the OS rate. Moreover, the seven-miRNA signature was an independent prognostic factor. In conclusion, this signature may serve as a prognostic biomarker and guide LIHC therapy, and it could even be used as an LIHC therapeutic target in the future. PMID- 29785038 TI - Reduced peak stimulated growth hormone is associated with hyperuricemia in obese children and adolescents. AB - The purpose of the study is to investigate whether reduced peak GH response to arginine-levodopa test is associated with hyperuricemia in obese children and adolescents. The study population consisted of a total sample of 78 obese and 30 normal-weight children and adolescents without known hypopituitarism. All participants underwent clinical examination and GH stimulation testing. IGF-1, lipid profile and other metabolic markers were assessed. The obese subjects were then divided into two groups according to the serum levels of uric acid. Results show that obese subjects had significantly lower peak GH, lower IGF-1 and similar height SDS than those in the control group. Children with hyperuricemia had significantly lower peak stimulated GH compared with non-hyperuricemia obese subjects. Results from logistic regression model showed that peak GH were negatively associated with hyperuricemia after controlling for age, gender, tanner stage, BMI SDS, IGF-1, blood pressure, HOMA-IR, lipids status. These data indicate that lower peak GH is positively associated with hyperuricemia in obese children and adolescents without known hypothalamic/pituitary disease after controlling BMI and insulin resistance, as well as other cardiometabolic risk factors. PMID- 29785039 TI - Extremely Low Frequency Electromagnetic Fields impair the Cognitive and Motor Abilities of Honey Bees. AB - Extremely low frequency electromagnetic field (ELF EMF) pollution from overhead powerlines is known to cause biological effects across many phyla, but these effects are poorly understood. Honey bees are important pollinators across the globe and due to their foraging flights are exposed to relatively high levels of ELF EMF in proximity to powerlines. Here we ask how acute exposure to 50 Hz ELF EMFs at levels ranging from 20-100 uT, found at ground level below powerline conductors, to 1000-7000 uT, found within 1 m of the conductors, affects honey bee olfactory learning, flight, foraging activity and feeding. ELF EMF exposure was found to reduce learning, alter flight dynamics, reduce the success of foraging flights towards food sources, and feeding. The results suggest that 50 Hz ELF EMFs emitted from powerlines may represent a prominent environmental stressor for honey bees, with the potential to impact on their cognitive and motor abilities, which could in turn reduce their ability to pollinate crops. PMID- 29785037 TI - Assessing the utility of frequency tagging for tracking memory-based reactivation of word representations. AB - Reinstatement of memory-related neural activity measured with high temporal precision potentially provides a useful index for real-time monitoring of the timing of activation of memory content during cognitive processing. The utility of such an index extends to any situation where one is interested in the (relative) timing of activation of different sources of information in memory, a paradigm case of which is tracking lexical activation during language processing. Essential for this approach is that memory reinstatement effects are robust, so that their absence (in the average) definitively indicates that no lexical activation is present. We used electroencephalography to test the robustness of a reported subsequent memory finding involving reinstatement of frequency-specific entrained oscillatory brain activity during subsequent recognition. Participants learned lists of words presented on a background flickering at either 6 or 15 Hz to entrain a steady-state brain response. Target words subsequently presented on a non-flickering background that were correctly identified as previously seen exhibited reinstatement effects at both entrainment frequencies. Reliability of these statistical inferences was however critically dependent on the approach used for multiple comparisons correction. We conclude that effects are not robust enough to be used as a reliable index of lexical activation during language processing. PMID- 29785041 TI - Dark septate endophytes isolated from a xerophyte plant promote the growth of Ammopiptanthus mongolicus under drought condition. AB - Dark septate endophytes (DSE) may facilitate plant growth and stress tolerance in stressful ecosystems. However, little is known about the response of plants to non-host DSE fungi isolated from other plants, especially under drought condition. This study aimed to seek and apply non-host DSE to evaluate their growth promoting effects in a desert species, Ammopiptanthus mongolicus, under drought condition. Nine DSE strains isolated from a super-xerophytic shrub, Gymnocarpos przewalskii, were identified and used as the non-host DSE. And DSE colonization rate (30-35%) and species composition in the roots of G. przewalskii were first reported. The inoculation results showed that all DSE strains were effective colonizers and formed a strain-dependent symbiosis with A. mongolicus. Specifically, one Darksidea strain, Knufia sp., and Leptosphaeria sp. increased the total biomass of A. mongolicus compared to non-inoculated plants. Two Paraconiothyrium strains, Phialophora sp., and Embellisia chlamydospora exhibited significantly positive effects on plant branch number, potassium and calcium content. Two Paraconiothyrium and Darksidea strains particularly decreased plant biomass or element content. As A. mongolicus plays important roles in fixing moving sand and delay desertification, the ability of certain DSE strains to promote desert plant growth indicates their potential use for vegetation recovery in arid environments. PMID- 29785040 TI - Archetypal transcriptional blocks underpin yeast gene regulation in response to changes in growth conditions. AB - The transcriptional responses of yeast cells to diverse stresses typically include gene activation and repression. Specific stress defense, citric acid cycle and oxidative phosphorylation genes are activated, whereas protein synthesis genes are coordinately repressed. This view was achieved from comparative transcriptomic experiments delineating sets of genes whose expression greatly changed with specific stresses. Less attention has been paid to the biological significance of 1) consistent, albeit modest, changes in RNA levels across multiple conditions, and 2) the global gene expression correlations observed when comparing numerous genome-wide studies. To address this, we performed a meta-analysis of 1379 microarray-based experiments in yeast, and identified 1388 blocks of RNAs whose expression changes correlate across multiple and diverse conditions. Many of these blocks represent sets of functionally related RNAs that act in a coordinated fashion under normal and stress conditions, and map to global cell defense and growth responses. Subsequently, we used the blocks to analyze novel RNA-seq experiments, demonstrating their utility and confirming the conclusions drawn from the meta-analysis. Our results provide a new framework for understanding the biological significance of changes in gene expression: 'archetypal' transcriptional blocks that are regulated in a concerted fashion in response to external stimuli. PMID- 29785042 TI - Inducible high-efficiency CRISPR-Cas9-targeted gene editing and precision base editing in African trypanosomes. AB - The Cas9 endonuclease can be programmed by guide RNA to introduce sequence specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency. We report a system for delivering tetracycline inducible Cas9 and guide RNA to Trypanosoma brucei. In these cells, targeted DNA cleavage and gene disruption can be achieved at close to 100% efficiency without further selection. Disruption of aquaglyceroporin (AQP2) or amino acid transporter genes confers resistance to the clinical drugs pentamidine or eflornithine, respectively, providing simple and robust assays for editing efficiency. We also use the new system for homology directed, precision base editing; a single-stranded oligodeoxyribonucleotide repair template was delivered to introduce a single AQP2 - T791G/L264R mutation in this case. The technology we describe now enables a range of novel programmed genome-editing approaches in T. brucei that would benefit from temporal control, high-efficiency and precision. PMID- 29785043 TI - Effect of Plant Density, Boron Nutrition and Growth Regulation on Seed Mass, Emergence and Offspring Growth Plasticity in Cotton. AB - Seed nutrients reserves have direct relationship with seed functional traits and influence offspring performance. Effects of plant density, foliage boron (B) nutrition and mepiquat chloride (MC) growth regulation on seed nutrients reserves, seed mass and production, and emergence and offspring growth traits of cotton were studied in two years field experiment. Seed nutrients reserves and seed mass were decreased at higher maternal plant density relative to lower plant density with concomitant decrease in emergence and offspring seedling growth. However, maternal foliage B nutrition and MC growth regulation enhanced seed nutrients reserves, seed mass, emergence and offspring seedling growth performance. There was a significant positive relationship between seed mass and seed nutrients reserves indicating that changes in nutrient availability/uptake in response to maternal ecological factors determine variation in seed functional traits. Nonetheless, seed mass was positively correlated with emergence percentage and negatively with emergence timing. Furthermore, variation in offspring seedling growth traits with seed mass indicated the significance of initial seed nutrients reserves for early seedling vigour and establishment. In conclusion, lower maternal plant density, B nutrition and MC growth regulation ensued in higher emergence and offspring seedling growth of cotton because of higher seed nutrient reserves and seed mass. PMID- 29785045 TI - An initial study on the effect of functional electrical stimulation in erectile dysfunction: a randomized controlled trial. AB - Erectile dysfunction (ED) affects approximately 150 million men worldwide. Functional electrical stimulation (FES) therapy has shown a high regenerative capacity for smooth muscle cells and, therefore, is being increasingly adopted. FES can be a beneficial treatment option when the cause of ED is related to degeneration of cavernous smooth muscle. To evaluate the impact of FES on erectile function in men with erectile dysfunction. Twenty-two patients with ED participated in this randomized clinical trial. Participants were randomly assigned to two groups: intervention (IG) or control (CG). IG participants underwent FES therapy (50 Hz/500 us) for a total of 4 weeks, divided into two weekly sessions lasting 15 min each, with intensity lower than the motor threshold. CG participants were treated with placebo FES and followed the same routine as the IG. Erectile function was assessed by the validated International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS), applied before and after treatment, and quality of life, by the WHOQOL questionnaire. Statistically significant differences in IIEF-5 and EHS were found between the IG and CG after treatment (p < 0.05), as well as a within-group difference in the IG when comparing the post-treatment periods (p < 0.0001) The WHOQOL revealed a significant difference between CG and IG after treatment (p < 0.05), as well as a within-group difference in the IG after treatment (p < 0.0001), except in the Environment domain, in which there was no difference between the pre- and post treatment periods (50.9 +/- 2.8 pre vs. 52.3 +/- 3.1 post). This trial showed that FES therapy may improve erectile function and quality of life in men with ED. PMID- 29785044 TI - The live cell DNA stain SiR-Hoechst induces DNA damage responses and impairs cell cycle progression. AB - SiR-Hoechst (SiR-DNA) is a far-red fluorescent DNA probe being used widely for time-lapse imaging of living cells that is reported to be minimally toxic at concentrations as high as 10-25 uM. However, measuring nuclear import of Cyclin B1, inhibition of mitotic entry, and the induction of gammaH2AX foci in cultured human cells reveals that SiR-Hoechst induces DNA damage responses and G2 arrest at concentrations well below 1 uM. SiR-Hoechst is useful for live cell imaging, but it should be used with caution and at the lowest practicable concentration. PMID- 29785046 TI - Relation between hypertension and erectile dysfunction: a meta-analysisof cross section studies. AB - Erectile dysfunction (ED) is a wide spread and troublesome problem in aging men. Many analyses of hypertensive patients suggest that the prevalence of ED in hypertensive populations is even higher. The purpose of this meta-analysis was to evaluate the relation between hypertension and ED. A literature review was performed to identify all cross-section studies about hypertension and erectile dysfunction. Sources included MEDLINE and EMBASE from 1966 to 2015. The reference lists of the retrieved studies were also investigated, and a meta-analysis were conducted. Eighteen cross-section studies involving a total of 41,943 participants and 10,151 cases of ED were used in this analysis. We found that risk of ED was increased with hypertension (summary OR = 1.84, 95% CI: 1.58-2.14, p < 0.000001). Adjusting for obesity, unfavorable lipid levels, alcohol abuse, physical activity, cigarette smoking, educational level and other lifestyle factors, hypertension was also associated with increased risk of ED (summary OR = 1.58, 95% CI: 1.35-1.86, p < 0.00001). The results of this meta-analysis support that hypertension is associated with an increased risk of ED. Further high quality prospective studies are needed to confirm this observation. PMID- 29785048 TI - Rubber versus forest on contested Asian land. PMID- 29785047 TI - Rationally designed AAV2 and AAVrh8R capsids provide improved transduction in the retina and brain. AB - The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO. In contrast to parental AAV2, the AAV2-HBKO vector displayed low-transduction activity following intravitreal delivery to the mouse eye; however, following its subretinal delivery, AAV2-HBKO resulted in significantly greater photoreceptor transduction. Intrastriatal delivery of AAV2 HBKO to mice facilitated widespread striatal and cortical expression, in contrast to the restricted transduction pattern of the parental AAV2 vector. Furthermore, we found that altering the surface charge on the AAVrh8R capsid by modifying the number of arginine residues on the capsid surface had a profound impact on subretinal transduction. The data further validate the potential of capsid engineering to improve AAV gene therapy vectors for clinical applications. PMID- 29785049 TI - Involvement of inhibitor kappa B kinase 2 (IKK2) in the regulation of vascular tone. AB - Inhibitor kappa B kinase 2 (IKK2) plays an essential role in the activation of nuclear factor kappa B (NF-kB). Recently, it has been suggested that IKK2 acts as a myosin light chain kinase (MLCK) and contributes to vasoconstriction in mouse aorta. However, the underlying mechanisms are still unknown. Therefore, we investigated whether IKK2 acts as a MLCK or regulates the activity of myosin light chain phosphatase (MLCP). Pressure myograph was used to measure vascular tone in rat mesenteric arteries. Immunofluorescence staining was performed to identify phosphorylation levels of MLC (ser19), MYPT1 (thr853 and thr696) and CPI 17 (thr38). SC-514 (IKK2 inhibitor, 50 MUM) induced relaxation in the mesenteric arteries pre-contracted with 70 mM high K+ solution or U-46619 (thromboxane analog, 5 MUM). The relaxation induced by SC-514 was increased in the arteries pre-contracted with U-46619 compared to arteries pre-contracted with 70 mM high K+ solution. U-46619-induced contraction was decreased by treatment of SC-514 in the presence of MLCK inhibitor, ML-7 (10 MUM). In the absence of intracellular Ca2+, U-46619 still induced contraction, which was decreased by treatment of SC 514. Furthermore, phosphorylation levels of MLC (ser19) and MYPT1 (thr853) were decreased by treatment of SC-514. IKK2 is involved in the vascular contraction through regulation of MLCP activity by phosphorylating MYPT1 at thr853 in rat mesenteric arteries. These findings suggest IKK2 could be a new pharmacological target for specific therapies of various vascular diseases. PMID- 29785050 TI - The tumor suppressor DLC1 inhibits cancer progression and oncogenic autophagy in hepatocellular carcinoma. AB - Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells. Mechanistic investigation revealed that DLC1 decreased TCF4 expression and the interaction between beta-catenin and TCF4, then inactivated Wnt/beta-catenin signaling. Additionally, DLC1 suppressed the ROCK1 activity and the dissociation of the Beclin1-Bcl2 complex, thereby inhibiting autophagy of HCC cells. In conclusion, our findings imply that loss of DLC1 contributes to the progression and oncogenic autophagy of HCC. PMID- 29785051 TI - Hyaluronan negatively regulates vascular calcification involving BMP2 signaling. AB - Vascular calcification is a highly regulated biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Hyaluronan (HA), a major structural component of the extracellular matrix in cartilage, has been shown to inhibit osteoblast differentiation. However, whether HA affects osteogenic differentiation and calcification of VSMCs remains unclear. In the present study, we used in vitro and ex vivo models of vascular calcification to investigate the role of HA in vascular calcification. Both high and low molecular weight HA treatment significantly reduced calcification of rat VSMCs in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Ex vivo study further confirmed the inhibitory effect of HA on vascular calcification. Similarly, HA treatment decreased ALP activity and expression of bone-related molecules including Runx2, BMP2 and Msx2. By contrast, inhibition of HA synthesis by 4-methylumbelliferone (4MU) promoted calcification of rat VSMCs. In addition, adenovirus-mediated overexpression of HA synthase 2 (HAS2), a major HA synthase in VSMCs, also inhibited calcification of VSMCs, whereas CRISPR/Cas9-mediated HAS2 knockout promoted calcification of rat A10 cells. Furthermore, we found that BMP2 signaling was inhibited in VSMCs after HA treatment. Recombinant BMP2 enhanced high calcium and phosphate-induced VSMC calcification, which can be blocked by HA treatment. Taken together, these findings suggest that HA inhibits vascular calcification involving BMP2 signaling. PMID- 29785052 TI - Observation of anisotropic magneto-Peltier effect in nickel. AB - The Peltier effect, discovered in 1834, converts a charge current into a heat current in a conductor, and its performance is described by the Peltier coefficient, which is defined as the ratio of the generated heat current to the applied charge current1,2. To exploit the Peltier effect for thermoelectric cooling or heating, junctions of two conductors with different Peltier coefficients have been believed to be indispensable. Here we challenge this conventional wisdom by demonstrating Peltier cooling and heating in a single material without junctions. This is realized through an anisotropic magneto Peltier effect in which the Peltier coefficient depends on the angle between the directions of a charge current and magnetization in a ferromagnet. By using active thermography techniques3-10, we observe the temperature change induced by this effect in a plain nickel slab. We find that the thermoelectric properties of the ferromagnet can be redesigned simply by changing the configurations of the charge current and magnetization, for instance, by shaping the ferromagnet so that the current must flow around a curve. Our experimental results demonstrate the suitability of nickel for the anisotropic magneto-Peltier effect and the importance of spin-orbit interaction in its mechanism. The anisotropic magneto Peltier effect observed here is the missing thermoelectric phenomenon in ferromagnetic materials-the Onsager reciprocal of the anisotropic magneto-Seebeck effect previously observed in ferromagnets-and its simplicity might prove useful in developing thermal management technologies for electronic and spintronic devices. PMID- 29785053 TI - Management of children and young people (CYP) with asthma: a clinical audit report. AB - An asthma attack or exacerbation signals treatment failure. Most attacks are preventable and failure to recognize risk of asthma attacks are well recognized as risk factors for future attacks and even death. Of the 19 recommendations made by the United Kingdom National Review of Asthma Deaths (NRAD) (1) only one has been partially implemented-a National Asthma Audit; however, this hasn't reported yet. The Harrow Clinical Commissioning Group (CCG) in London implemented a clinical asthma audit on 291 children and young people aged under 19 years (CYP) who had been treated for asthma attacks in 2016. This was funded as a Local Incentive Scheme (LIS) aimed at improving quality health care delivery. Two years after the publication of the NRAD report it is surprising that risks for future attacks were not recognized, that few patients were assessed objectively during attacks and only 10% of attacks were followed up within 2 days. However, it is encouraging that CYP hospital admissions following the audit were reduced by 16%, with clear benefit for patients, their families and the local health economy. This audit has provided an example of how clinicians can focus learning on patients who have had asthma attacks and utilize these events as a catalyst for active reflection in particular on modifiable risk factors. Through identification of these risks and active optimization of management, preventable asthma attacks could become 'never events'. PMID- 29785054 TI - Correlating the nanostructure of Al-oxide with deposition conditions and dielectric contributions of two-level systems in perspective of superconducting quantum circuits. AB - This work is concerned with Al/Al-oxide(AlOx)/Al-layer systems which are important for Josephson-junction-based superconducting devices such as quantum bits. The device performance is limited by noise, which has been to a large degree assigned to the presence and properties of two-level tunneling systems in the amorphous AlOx tunnel barrier. The study is focused on the correlation of the fabrication conditions, nanostructural and nanochemical properties and the occurrence of two-level tunneling systems with particular emphasis on the AlOx layer. Electron-beam evaporation with two different processes and sputter deposition were used for structure fabrication, and the effect of illumination by ultraviolet light during Al-oxide formation is elucidated. Characterization was performed by analytical transmission electron microscopy and low-temperature dielectric measurements. We show that the fabrication conditions have a strong impact on the nanostructural and nanochemical properties of the layer systems and the properties of two-level tunneling systems. Based on the understanding of the observed structural characteristics, routes are suggested towards the fabrication of Al/AlOx/Al-layers systems with improved properties. PMID- 29785056 TI - Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA. AB - Uracil in DNA can be generated by cytosine deamination or dUMP misincorporation; however, its distribution in the human genome is poorly understood. Here we present a selective labeling and pull-down technology for genome-wide uracil profiling and identify thousands of uracil peaks in three different human cell lines. Surprisingly, uracil is highly enriched at the centromere of the human genome. Using mass spectrometry, we demonstrate that human centromeric DNA contains a higher level of uracil. We also directly verify the presence of uracil within two centromeric uracil peaks on chromosomes 6 and 11. Moreover, centromeric uracil is preferentially localized within the binding regions of the centromere-specific histone CENP-A and can be excised by human uracil-DNA glycosylase UNG. Collectively, our approaches allow comprehensive analysis of uracil in the human genome and provide robust tools for mapping and future functional studies of uracil in DNA. PMID- 29785055 TI - Mindfulness training induces structural connectome changes in insula networks. AB - Although mindfulness meditation is known to provide a wealth of psychological benefits, the neural mechanisms involved in these effects remain to be well characterized. A central question is whether the observed benefits of mindfulness training derive from specific changes in the structural brain connectome that do not result from alternative forms of experimental intervention. Measures of whole brain and node-level structural connectome changes induced by mindfulness training were compared with those induced by cognitive and physical fitness training within a large, multi-group intervention protocol (n = 86). Whole-brain analyses examined global graph-theoretical changes in structural network topology. A hypothesis-driven approach was taken to investigate connectivity changes within the insula, which was predicted here to mediate interoceptive awareness skills that have been shown to improve through mindfulness training. No global changes were observed in whole-brain network topology. However, node-level results confirmed a priori hypotheses, demonstrating significant increases in mean connection strength in right insula across all of its connections. Present findings suggest that mindfulness strengthens interoception, operationalized here as the mean insula connection strength within the overall connectome. This finding further elucidates the neural mechanisms of mindfulness meditation and motivates new perspectives about the unique benefits of mindfulness training compared to contemporary cognitive and physical fitness interventions. PMID- 29785057 TI - Computational redesign of enzymes for regio- and enantioselective hydroamination. AB - Introduction of innovative biocatalytic processes offers great promise for applications in green chemistry. However, owing to limited catalytic performance, the enzymes harvested from nature's biodiversity often need to be improved for their desired functions by time-consuming iterative rounds of laboratory evolution. Here we describe the use of structure-based computational enzyme design to convert Bacillus sp. YM55-1 aspartase, an enzyme with a very narrow substrate scope, to a set of complementary hydroamination biocatalysts. The redesigned enzymes catalyze asymmetric addition of ammonia to substituted acrylates, affording enantiopure aliphatic, polar and aromatic beta-amino acids that are valuable building blocks for the synthesis of pharmaceuticals and bioactive compounds. Without a requirement for further optimization by laboratory evolution, the redesigned enzymes exhibit substrate tolerance up to a concentration of 300 g/L, conversion up to 99%, beta-regioselectivity >99% and product enantiomeric excess >99%. The results highlight the use of computational design to rapidly adapt an enzyme to industrially viable reactions. PMID- 29785058 TI - Effects of maternal obstructive sleep apnea on fetal growth: a case-control study. AB - OBJECTIVE: To investigate whether maternal obstructive sleep apnea (OSA) is associated with changes in fetal growth trajectory. STUDY DESIGN: Retrospective review of pregnant women who underwent overnight polysomnography. Fetal growth was estimated using sonographic biometric measurements obtained during routine prenatal care. Customized estimated fetal weight and birth weight centiles were calculated and impaired fetal growth was defined as birth weight <10th centile or a slowing of fetal growth by >33% during the last trimester. Logistic regression models were used to determine the relationship between maternal OSA and altered fetal growth after adjusting for potential covariates. RESULTS: There were 48 women without and 31 women with OSA. There were no differences in the proportion of infants with birth weight <10th centile between women with and without OSA (23 vs. 25%, p = 1.0), However, the presence of maternal OSA was predictive of impaired fetal growth (aOR 3.9, 95% CI 1.2-12.6). Logistic regression models were repeated using only a slowing of fetal growth in the 3rd trimester (excluding birth weight <10th centile) and OSA predicted a slowing in fetal growth across the 3rd trimester (aOR 3.6, 95% CI 1.4-9.4). Fourteen additional women were treated with positive airway pressure during pregnancy; fetal growth was not significantly different in these women compared to controls. CONCLUSION: Obstructive sleep apnea is independently associated with altered fetal growth, which appears to be ameliorated with use of positive airway pressure. PMID- 29785059 TI - Early NT-proBNP levels as a screening tool for the detection of hemodynamically significant patent ductus arteriosus during the first week of life in very low birth weight infants. AB - OBJECTIVE: To assess whether early NT-ProBNP can identify the need for echocardiographic assessment of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. STUDY DESIGN: Prospective observational study of infants with a gestational age <=32 weeks. Echocardiographic assessment and NT-proBNP measurement were performed at 48-96 h. ROC curves were generated to assess optimal cutoffs to detect HsPDA and predict the need for treatment. RESULTS: Eighty-five patients were included. HsPDA was present in 28 infants (37.6%), and 22 (25.8%) received treatment. The optimal NT-proBNP cutoff for the detection of HsPDA was 5099 pg/mL (sensitivity 94%, specificity 82%, area under the curve 0.941, P < 0.001). Only 1 child with NT-proBNP levels <5099 pg/mL was ultimately treated for PDA. NT-proBNP screening could have avoided 45 of 85 routine echocardiograms (53%). CONCLUSION: NT-proBNP screening at 48-96 h of life may identify preterm infants at low risk for HsPDA, improving PDA management. PMID- 29785060 TI - Cost effectiveness of vitamin c supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma. AB - OBJECTIVE: To determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma related mortality, and associated costs. STUDY DESIGN: A decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions. RESULT: Additional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort. CONCLUSION: Vitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma. PMID- 29785061 TI - Targeted neonatal echocardiography (TNE) consult service in a large tertiary perinatal center in Canada. AB - OBJECTIVE: To describe the utilization and study the factors associated with the impact on clinical management of a new TNE consultation service in a perinatal center. METHODS: This retrospective cohort study included all neonates who underwent TNE consultation at the neonatal unit of Mount Sinai Hospital in Toronto, Canada (November 2011 and July 2015). The consults that had "impact" were defined as those that led to a TNE suggested change in the clinical management within 6 h of its recommendation. Logistic regression analysis was performed to identify factors associated with a change in clinical management following the consultation. RESULTS: A total of 553 consults were performed for 268 infants (gestational age: 27 +/- 4 weeks and age at initial consult: 16 (5, 34) days). Patent ductus arteriosus (PDA, 61%), suspected pulmonary hypertension (PH, 27%), and systemic hypotension (SH, 9%) were the common indications. The average consultations increased from 9 in 2012-2013 to 20 per month in 2014-2015. Forty eight percent of consults had an impact on clinical management (PDA scans: 38%, PH: 58%, and SH: 81%, p < 0.01 between all). Male gender (adjusted odds ratio (95% confidence interval): 1.9 (1.0, 3.5); p = 0.04), mechanical ventilation (2.43 (1.2, 4.9); p = 0.01), and scans for PH (7.1 (2.2, 23.2); p < 0.01) and SH (2.6 (1.1, 6.5); p = 0.03) were independently associated with the impact on clinical management. TNE consults identified all incidental cases of major structural defects (n = 4), and six out of ten minor diagnoses. CONCLUSIONS: TNE consult service demonstrated an increasing utilization and a significant impact on clinical management over time especially for non-PDA indications and in situations of high-illness severity. Although, all major cardiac defects were identified, some minor congenital defects were missed by TNEs. PMID- 29785062 TI - Outcomes of hypoxic respiratory failure at birth associated with previable rupture of membranes. AB - OBJECTIVE: To characterize clinical outcomes of infants born after previable rupture of membranes (pROM, < 23 weeks gestation and latency period >= 2 weeks) in relation to refractory hypoxic respiratory failure (rHRF). STUDY DESIGN: pROM neonates categorized as rHRF (FiO2 > 0.6 for >= 2 h) and treated (high frequency ventilation + inhaled nitric oxide) were compared with no rHRF group. Primary outcome was survival until discharge. Factors associated with rHRF and mortality were identified. RESULT: Overall, mortality and disability rates were 28% and 22%, respectively. Treated rHRF group (n = 32) had longer period of ROM, mortality was (31% vs. 14%; p = 0.20), with similar survival-without-disability (54% vs. 47%; p = 0.67). Higher gestational age at birth [1.57 (1.03,2.39)] and cesarean delivery [12.6 (1.22,125)] were associated with increased survival. CONCLUSION: Birth after pROM is associated with high rates of adverse outcomes, independent of latency period. Following treatment, rHRF infants may have similar long-term outcomes as those without rHRF. PMID- 29785063 TI - The Comprehension Problems of Children with Poor Reading Comprehension despite Adequate Decoding: A Meta-Analysis. AB - The purpose of this meta-analysis was to examine the comprehension problems of children who have a specific reading comprehension deficit (SCD), which is characterized by poor reading comprehension despite adequate decoding. The meta analysis included 86 studies of children with SCD who were assessed in reading comprehension and oral language (vocabulary, listening comprehension, storytelling ability, and semantic and syntactic knowledge). Results indicated that children with SCD had deficits in oral language (d = -0.78, 95% CI [-0.89, 0.68], but these deficits were not as severe as their deficit in reading comprehension (d = -2.78, 95% CI [-3.01, -2.54]). When compared to reading comprehension age-matched normal readers, the oral language skills of the two groups were comparable (d = 0.32, 95% CI [-0.49, 1.14]), which suggests that the oral language weaknesses of children with SCD represent a developmental delay rather than developmental deviance. Theoretical and practical implications of these findings are discussed. PMID- 29785064 TI - Identification of relevant subtypes via preweighted sparse clustering. AB - Cluster analysis methods are used to identify homogeneous subgroups in a data set. In biomedical applications, one frequently applies cluster analysis in order to identify biologically interesting subgroups. In particular, one may wish to identify subgroups that are associated with a particular outcome of interest. Conventional clustering methods generally do not identify such subgroups, particularly when there are a large number of high-variance features in the data set. Conventional methods may identify clusters associated with these high variance features when one wishes to obtain secondary clusters that are more interesting biologically or more strongly associated with a particular outcome of interest. A modification of sparse clustering can be used to identify such secondary clusters or clusters associated with an outcome of interest. This method correctly identifies such clusters of interest in several simulation scenarios. The method is also applied to a large prospective cohort study of temporomandibular disorders and a leukemia microarray data set. PMID- 29785066 TI - Low Temperature CMUT Fabrication Process with Dielectric Lift-off Membrane Support for Improved Reliability. AB - This paper reports an improved CMOS compatible low temperature sacrificial layer fabrication process for Capacitive Micromachined Ultrasonic Transducers (CMUTs). The process adds the fabrication step of silicon oxide evaporation which is followed by a lift-off step to define the membrane support area without a need for an extra mask. This simple addition improves reliability by reducing the electric field between the top and bottom electrodes everywhere except the moving membrane without affecting the vacuum gap thickness. Furthermore, the parasitic capacitance which degrades the CMUT receive performance is reduced. A 1-D CMUT array suitable for Intracardiac Echocardiography (ICE) imaging with 9MHz center frequency is fabricated using this method. Detailed electrical and acoustic testing indicates adequate performance of the devices for ICE in agreement with simulations. Long term output pressure testing with more than 2*1011 pulsing cycles and environmental testing demonstrate the efficacy of the approach for improved reliability as compared to devices without the additional membrane support layer. PMID- 29785065 TI - Relation between coping and posttrauma cognitions on PTSD in a combat-trauma population. AB - Individual differences in cognitive processes and coping behaviors play a role in the development and maintenance of posttraumatic stress disorder (PTSD). Given the large numbers of combat-exposed service members returning from the Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) conflicts, exploring individual differences in cognitive-affective processes is important for informing our understanding of PTSD etiology and early intervention in military samples. The present study examined the unique main and interactive effects of negative posttrauma cognitions (i.e., negative beliefs about self [NS], the world [NW], and self-blame [SB]) and coping strategies (i.e., positive behavioral, positive cognitive, avoidant coping, and social and emotional coping) on PTSD diagnosis within 155 (Mage = 30.7, SD = 4.48) OEF/OIF/OND combat trauma-exposed veterans recruited from an ongoing study examining the effects of combat trauma and stress reactivity. In the final, stepwise logistic regression analysis, avoidant coping, but no other coping strategy, was significantly positively related to PTSD diagnosis in the initial step. Higher levels of NS, but not NW, were significantly associated with having a PTSD diagnosis, while SB was associated with decreased likelihood of PTSD, above and beyond coping strategies. A significant interaction effect was found between NS and positive cognitive coping, such that greater positive cognitive coping weakened the relationship between NS and PTSD. Examining and addressing coping behaviors and negative thoughts of self jointly may benefit assessment and intervention approaches in a combat-trauma population. PMID- 29785067 TI - In silico physicochemical characterization and topology analysis of Respiratory burst oxidase homolog (Rboh) proteins from Arabidopsis and rice. AB - NADPH oxidase (NOX) is a key enzyme involved in the production of apoplastic superoxide (O2-), a type of reactive oxygen species (ROS). Plant Noxes are the homologs of mammalian NADPH oxidase's catalytic subunit and are documented as respiratory burst oxidase homologs (Rbohs). A number of studies have reported their diverse functions in combating various stresses and in plant growth and development. In the present study, a total of 19 Rboh proteins (10 from Arabidopsis thaliana and 9 from Oryza sativa Japonica) were analyzed. We employed in silico approaches to compute the physiochemical properties (molecular weight, isoelectric point, total number of negatively and positively charged residues, extinction coefficient, half-life, instability and aliphatic index, grand average of hydropathicity, amino acid percentage). We observed a lot of variability in these parameters among the Rbohs accounting for their functional diversification. Their topological analysis, subcellular localization and signal peptide detection are also performed. To the best of our knowledge, the present study report on in silico physiochemical characterization, topology analysis, subcellular localization and signal peptide detection of Rboh proteins within two model plants. The study elucidates the variations in the key properties among Rbohs proteins, which may be responsible for their functional multiplicity. PMID- 29785068 TI - Molecular dynamics simulation (MDS) analysis of Vibrio cholerae ToxT virulence factor complexed with docked potential inhibitors. AB - The ToxT transcription factor mediates the transcription of the two major virulence factors in Vibrio cholerae. It has a DNA binding domain made of alpha4, alpha5, alpha6, alpha7, alpha8, alpha9 and alpha10 helices that is responsible for the transcription of virulence genes. Therefore, it is of interest to screen ToxT against the ZINC ligand database containing data for a million compounds. The QSAR model identified 40 top hits for ToxT. Two target protein complexes with ligands Lig N1 and Lig N2 with high score were selected for molecular dynamics simulation. Simulation data shows that ligands are stable in the DNA binding domain of ToxT. Moreover, Lig N1 and Lig N2 passed pharmacological as well as ADME filters along with g-mmpbsa analysis with binding affinity of -199.831 kJ/mol for Lig N1 and - 286.951 kJ/mol for Lig N2. Moreover, no Lipinski and PhysChem violations were identified. It is further observed that these compounds were not inhibitors of P-glycoprotein, CYP450 and renal organic cation transporters. The LD50 of 2.5804 mol/kg for Lig N1 and 2.7788 mol/kg for Lig N2 was noted with acceptable toxicity index. PMID- 29785069 TI - Genetic characterization of Chikungunya virus 2009 isolates from South India. AB - Chikungunya Virus (CHIKV) is a single stranded positive sense enveloped RNA virus. Re-emergence of CHIKV caused a massive outbreak with severe clinical manifestation affecting multiple organs. The genetic diversity of CHIKV, which caused recurring outbreaks in India, was studied. Blood samples were collected from suspected human cases of CHIKV infection in Chennai, Tamil Nadu and three Northern districts of Kerala in Southern India during the CHIKV outbreak in 2009. A partial E2 gene segment was amplified by RT-PCR. Among 119 samples 37 samples were positive for CHIKV by RT-PCR. Phylogenetic analysis revealed that the isolated sequences belonged to Indian Ocean Lineage (IOL) of ECSA genotype. The mutational analysis revealed the presence of substitutions such as S299N, T312M, A344T, S375T, V386G, W339R and S375P in the current study. In addition, a novel mutation V386G was observed in all the sequences. Two isolates found with unique substitutions W339R and S375P are reported. The structural analysis of the wild type and mutant proteins revealed that the structural changes are accompanied by modification in the intraprotein interactions. PMID- 29785070 TI - Analysis of antibiotics resistant genes in different strains of Staphylococcus aureus. AB - The control of Staphylococcus aureus infection is being hampered by methicillin and other resistant strains. The identification of the unique antibiotic resistant genes from the genomes of various strains of S. aureus is of interest. We analyzed 11 S. aureus genomes sequences for Antibiotics Resistance Genes (ARGs) using CARD 2017 platform. We identified 32 ARGs across 11 S. aureus strains. Tet(38), norB, lmrB, mepA and mepR were present across genomes except for S. aureus strain UTSW MRSA 55. The mepA and mepR were found across 11 different genomes. However, FosB3, vgaALC, mphC and SAT-4 were found in UTSW MRSA 55, S.a. strain ISU935 and S.a. strain FDAARGOS_159. The prevalent mode of mechanism of antibiotics resistant was efflux pump complex or subunit conferring antibiotic resistance as well as protein(s). Analysis of norB, ImrB, norA, ImrB, tet (38), sav1866 and mecA have 12 to 14 TMHs. The results help in the understanding of Staphylococcus aureus pathogenesis in the context of antibiotic resistance. PMID- 29785071 TI - Identification of cis-regulatory elements associated with salinity and drought stress tolerance in rice from co-expressed gene interaction networks. AB - Rice, a staple food crop, is often subjected to drought and salinity stresses thereby limiting its yield potential. Since there is a cross talk between these abiotic stresses, identification of common and/or overlapping regulatory elements is pivotal for generating rice cultivars that showed tolerance towards them. Analysis of the gene interaction network (GIN) facilitates identifying the role of individual genes and their interactions with others that constitute important molecular determinants in sensing and signaling cascade governing drought and/or salinity stresses. Identification of the various cis-regulatory elements of the genes constituting GIN is equally important. Here, in this study graphical Gaussian model (GGM) was used for generating GIN for an array of genes that were differentially regulated during salinity and/or drought stresses to contrasting rice cultivars (salt-tolerant [CSR11], salt-sensitive [VSR156], drought-tolerant [Vandana], drought-sensitive [IR64]). Whole genome transcriptom profiling by using microarray were employed in this study. Markov Chain completed co expression analyses of differentially expressed genes using Dynamic Bayesian Network, Probabilistic Boolean Network and Steady State Analysis. A compact GIN was identified for commonly co-expressed genes during salinity and drought stresses with three major hubs constituted by Myb2 transcription factor (TF), phosphoglycerate kinase and heat shock protein (Hsp). The analysis suggested a pivotal role of these genes in salinity and/or drought stress responses. Further, analysis of cis-regulatory elements (CREs) of commonly differentially expressed genes during salinity and drought stresses revealed the presence of 20 different motifs. PMID- 29785072 TI - Insights from the Molecular Modelling and Docking Analysis of AIF-NLS complex to infer Nuclear Translocation of the Protein. AB - Apoptosis Inducing Factor protein has a dual role depending on its localization in mitochondrion (energy production) and nucleus (induces apoptosis). Cell damage transports this protein to nucleus which otherwise favors mitochondrion. The alteration of Nuclear Localisation Signal tags could aid nuclear translocation. In this study, apoptosis inducing factor protein (AIF) was conjugated with strong NLS tags and its binding affinity with Importin was studied using in silico approaches such as molecular modeling and docking. This aims to improve the docking affinity of the AIF-Importin complex thus allowing for nuclear translocation, in order to induce caspase-independent apoptosis of the cell. PMID- 29785073 TI - Scale-free networks in metabolomics. AB - Metabolomics is an expanding discipline in biology. It is the process of portraying the phenotype of a cell, tissue or species organism using a comprehensive set of metabolites. Therefore, it is of interest to understand complex systems such as metabolomics using a scale-free topology. Genetic networks and the World Wide Web (WWW) are described as networks with complex topology. Several large networks have vertex connectivity that goes beyond a scale-free power-law distribution. It is observed that (a) networks expand constantly by the addition of recent vertices, and (b) recent vertices attach preferentially to sites that are already well connected. Scalefree networks are determined with precision using vital features such as a structure, a disease and a patient. This is pertinent to the understanding of complex systems such as metabolomics. Hence, we describe the relevance of scale-free networks in the understanding of metabolomics in this article. PMID- 29785074 TI - Challenges in diagnosis of pancreatic cancer. AB - Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease. PMID- 29785075 TI - Biliary strictures complicating living donor liver transplantation: Problems, novel insights and solutions. AB - Biliary stricture complicating living donor liver transplantation (LDLT) is a relatively common complication, occurring in most transplant centres across the world. Cases of biliary strictures are more common in LDLT than in deceased donor liver transplantation. Endoscopic management is the mainstay for biliary strictures complicating LDLT and includes endoscopic retrograde cholangiography, sphincterotomy and stent placement (with or without balloon dilatation). The efficacy and safety profiles as well as outcomes of endoscopic management of biliary strictures complicating LDLT is an area that needs to be viewed in isolation, owing to its unique set of problems and attending complications; as such, it merits a tailored approach, which is yet to be well established. The diagnostic criteria applied to these strictures are not uniform and are over reliant on imaging studies showing an anastomotic narrowing. It has to be kept in mind that in the setting of LDLT, a subjective anastomotic narrowing is present in most cases due to a mismatch in ductal diameters. However, whether this narrowing results in a functionally significant narrowing is a question that needs further study. In addition, wide variation in the endotherapy protocols practised in most centres makes it difficult to interpret the results and hampers our understanding of this topic. The outcome definition for endotherapy is also heterogenous and needs to be standardised to allow for comparison of data in this regard and establish a clinical practice guideline. There have been multiple studies in this area in the last 2 years, with novel findings that have provided solutions to some of these issues. This review endeavours to incorporate these new findings into the wider understanding of endotherapy for biliary strictures complicating LDLT, with specific emphasis on diagnosis of strictures in the LDLT setting, endotherapy protocols and outcome definitions. An attempt is made to present the best management options currently available as well as directions for future research in the area. PMID- 29785076 TI - Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease. AB - Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD. PMID- 29785077 TI - Mediterranean diet and nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet (MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and anti-oxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition. PMID- 29785079 TI - Decreasing recurrent bowel obstructions, improving quality of life with physiotherapy: Controlled study. AB - AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy vs no treatment. METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, which is the normal course for patients with recurring SBO. Comparison of the groups allowed us to assess changes when the physiotherapy was added as an adjunct treatment for patients with recurring SBO. RESULTS: Despite histories of more prior hospitalizations, obstructions, surgeries, and years impacted by bowel issues, the 103 CPA-treated subjects reported a significantly lower rate of repeat SBO than 136 untreated controls (total obstructions P = 0.0003; partial obstructions P = 0.0076). Subjects treated with the therapy demonstrated significant improvements in five of six total domains in the validated Small Bowel Obstruction Questionnaire (SBO-Q). Domains of diet, pain, gastrointestinal symptoms, quality of life (QOL) and pain severity when compared to post CPA treatment were significantly improved (P < 0.0001). The medication domain was not changed in the CPA treated group (P = 0.176). CONCLUSION: CPA physical therapy was effective for patients with adhesive SBO with significantly lower recurrence rate, improvement in reported symptoms and overall quality of life of subjects. PMID- 29785078 TI - Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy. AB - AIM: To detect hyper-conserved regions in the hepatitis B virus (HBV) X gene (HBX) 5' region that could be candidates for gene therapy. METHODS: The study included 27 chronic hepatitis B treatment-naive patients in various clinical stages (from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeAg-negative and HBeAg-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/mL, the HBX 5' end region [nucleotide (nt) 1255-1611] was PCR-amplified and submitted to next generation sequencing (NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences (haplotypes) obtained by NGS. Conservation at the HBx protein amino acid (aa) level was also analyzed. RESULTS: NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample (2487-9279, IQR 2817). In 14/27 patients (51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper conserved nucleotide regions, one in the HBX upstream non-coding region (nt 1255 1286) and the other in the 5' end coding region (nt 1519-1603). This last region coded for a conserved amino acid region (aa 63-76) that partially overlaps a Kunitz-like domain. CONCLUSION: Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype. PMID- 29785080 TI - Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis. AB - AIM: To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC). METHODS: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English. RESULTS: A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number <= 400 (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, P = 0.000). CONCLUSION: Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value. PMID- 29785081 TI - Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: Case report and review of the literature. AB - We report the first application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-year-old woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m2 and doxorubicin at 1.5 mg/m2 for 30 min at 37 degrees C. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis (RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures. PMID- 29785083 TI - Treatment of high myopia/myopic astigmatism with a combination of WaveLight Contoura with LYRA protocol and wavefront-optimized treatment. AB - Purpose: The aim of this article was to demonstrate how WaveLight Contoura and wavefront optimization (WFO) can be used together to treat high myopia/myopic astigmatism corrections. Materials and methods: A retrospective analysis was conducted on 24 consecutive myopic/myopic astigmatism eyes that exceeded the Contoura labeling of -8.00 with -3.00 D of astigmatism. Residual correction after Contoura with Layer Yolked Reduction of Astigmatism protocol was treated with WFO Contoura LASIK correction. All patients had 3 months of follow-up. Accuracy to the desired refractive goal was assessed by postoperative refraction, regression, postoperative vision, and anecdotal subjective night vision quality. Results: No eyes lost best-corrected visual acuity (BCVA), and 54% of eyes gained BCVA. Out of 22 distance eyes, five achieved 20/15 or better, 18 achieved 20/20 vision, two achieved 20/25, and three achieved 20/30 vision. Preoperatively, only 14 eyes could achieve 20/20 vision. No night vision issues were observed in anecdotal reporting by patients except for those who needed enhancements that had not yet been performed. Conclusion: Treatment of high myopia/astigmatism with this combination of Contoura with LYRA protocol and WFO results in excellent visual outcomes, large ablation zones on topography, and few subjective reported night vision issues. PMID- 29785082 TI - Control-matched comparison of refractive and visual outcomes between small incision lenticule extraction and femtosecond laser-assisted LASIK. AB - Purpose: This retrospective case-matched study aimed to compare visual and refractive outcomes between small incision lenticule extraction (SMILE) and LASIK. Patients and methods: Patients who underwent SMILE (34 eyes of 23 patients) or LASIK (34 eyes of 24 patients) were enrolled and matched according to preoperative manifest refractive spherical equivalents. The mean preoperative manifest refractive spherical equivalent was -4.69+/-0.6 and -4.67+/-0.64 D in the SMILE and LASIK groups, respectively. The safety, efficacy, and predictability were compared 3 months after surgery. Changes in corneal refractive power from the center to peripheral points and their maintenance ratios were analyzed and compared between the two groups. Results: In the SMILE and LASIK groups, 82.4% and 85.3% of patients, respectively, achieved 20/13 or better uncorrected distance visual acuity (p=1.00). There were no eyes that lost two or more lines of corrected distance visual acuity in either group. The maintenance ratios of corneal refractive power changes at the peripheral points in the SMILE group were significantly higher than those in the LASIK group (p<0.05). Conclusion: Both groups achieved similar high efficacy and safety. SMILE surgery resulted in higher refractive power correction in the peripheral cornea than LASIK surgery. PMID- 29785084 TI - Impact of virtual reality simulation on learning barriers of phacoemulsification perceived by residents. AB - Objective: To identify residents' perceived barriers to learning phacoemulsification surgical procedures and to evaluate whether virtual reality simulation training changed these perceptions. Design: The ophthalmology residents undertook a simulation phacoemulsification course and proficiency assessment on the Eyesi system using the previously validated training modules of intracapsular navigation, anti-tremor, capsulorrhexis, and cracking/chopping. A cross-sectional, multicenter survey on the perceived difficulties in performing phacoemulsification tasks on patients, based on the validated International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR), using a 5-point Likert scale (1 = least and 5 = most difficulty), was conducted among residents with or without prior simulation training. Mann Whitney U tests were carried out to compare the mean scores, and multivariate regression analyses were performed to evaluate the association of lower scores with the following potential predictors: 1) higher level trainee, 2) can complete phacoemulsification most of the time (>90%) without supervisor's intervention, and 3) prior simulation training. Setting: The study was conducted in ophthalmology residency training programs in five regional hospitals in Hong Kong. Results: Of the 22 residents, 19 responded (86.3%), of which 13 (68.4%) had completed simulation training. Nucleus cracking/chopping was ranked highest in difficulty by all respondents followed by capsulorrhexis completion and nucleus rotation/manipulation. Respondents with prior simulation training had significantly lower difficulty scores on these three tasks (nucleus cracking/chopping 3.85 vs 4.75, P = 0.03; capsulorrhexis completion 3.31 vs 4.40, P = 0.02; and nucleus rotation/manipulation 3.00 vs 4.75, P = 0.01). In multivariate analyses, simulation training was significantly associated with lower difficulty scores on these three tasks. Conclusion: Residents who had completed Eyesi simulation training had higher confidence in performing the most difficult tasks perceived during phacoemulsification. PMID- 29785085 TI - "Wet" transepithelial phototherapeutic keratectomy in the management of persistent epithelial defects in the graft. AB - Purpose: This study aimed to evaluate the efficacy of "wet" transepithelial phototherapeutic keratectomy (TE-PTK) for treating persistent epithelial defects (PEDs) in the corneal graft following penetrating keratoplasty (PKP). Methods: This study describes a noncomparative, prospective interventional case series. Patients with post-PKP graft epithelial defects lasting >3 months despite previous treatments with extensive wear soft contact lenses, amniotic membrane transplantation, and tarsorrhaphy were treated with wet TE-PTK. A wet TE-PTK procedure including a "wet ablation" step was performed using the EC-5000 excimer laser. Follow-up visits were at post-PTK days 3, 5, 10, and 30, and at each month thereafter. Results: Eight patients (8 eyes; 5 men and 3 women; mean age, 51.3+/ 14.3 years; mean follow-up period, 9.1+/-3.0 months) were included in this study. The mean best-corrected visual acuity was 1.76+/-0.28 log minimum angle of resolution (logMAR) at baseline and improved to 1.1+/-0.22 logMAR at 10 days postoperatively (p=0.0156; the improvement was significant). This effect remained stable throughout the remainder of the follow-up period. The mean time from wet TE-PTK to complete reepithelization was 4.3+/-1.3 days. Conclusion: Wet TE-PTK appears to be effective for patients with post-PKP PEDs in the corneal graft who have failed conservative measures or previous surgical interventions. PMID- 29785086 TI - The utilization of an ocular wound chamber on corneal epithelial wounds. AB - Purpose: Currently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries. Materials and methods: A depilatory cream (NairTM, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (Algerbrush(r)II). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal(r)) or HPMC liquid (GenTeal(r)) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist. Results: Corneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls. Conclusions: This study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel. PMID- 29785087 TI - Transcriptomic Impacts of Rumen Epithelium Induced by Butyrate Infusion in Dairy Cattle in Dry Period. AB - The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function. Ruminal infusion of butyrate was following 0-hour sampling (baseline controls) and continued for 168 hours at a rate of 5.0 L/day of a 2.5 M solution as a continuous infusion. Following the 168-hour infusion, the infusion was stopped, and cows were maintained on the basal lactation ration for an additional 168 hours for sampling. Rumen epithelial samples were serially collected via biopsy through rumen fistulae at 0-, 24-, 72-, and 168-hour (D1, D3, D7) and 168-hour post infusion (D14). In comparison with pre-infusion at 0 hours, a total of 3513 genes were identified to be impacted in the rumen epithelium by butyrate infusion at least once at different sampling time points at a stringent cutoff of false discovery rate (FDR) < 0.01. The maximal effect of butyrate was observed at day 7. Among these impacted genes, 117 genes were responsive consistently from day 1 to day 14, and another 42 genes were lasting through day 7. Temporal effects induced by butyrate infusion indicate that the transcriptomic alterations are very dynamic. Gene ontology (GO) enrichment analysis revealed that in the early stage of rumen butyrate infusion (on day 1 and day 3 of butyrate infusion), the transcriptomic effects in the rumen epithelium were involved with mitotic cell cycle process, cell cycle process, and regulation of cell cycle. Bioinformatic analysis of cellular functions, canonical pathways, and upstream regulator of impacted genes underlie the potential mechanisms of butyrate-induced gene expression regulation in rumen epithelium. The introduction of transcriptomic and bioinformatic technologies to study nutrigenomics in the farm animal presented a new prospect to study multiple levels of biological information to better apprehend the whole animal response to nutrition, physiological state, and their interactions. The nutrigenomics approach may eventually lead to more precise management of utilization of feed resources in a more effective approach. PMID- 29785088 TI - Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation. AB - Background: Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation. Methods: Molecular docking, conventional molecular dynamics (MD) simulations, free energy calculations, and umbrella sampling (US) simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R) mutation. Results: JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib resistance, not JH VIII-157-02. In addition, US simulations prove JH-VIII-157-02 has similar dissociative processes from both ALKWT and ALKG1202R, while alectinib is more easily dissociated from ALKG1202R than from ALKWT, thus indicating lesser residence time. Conclusion: Both the binding affinity and the drug residence time should be emphasized in rational drug design to overcome the G1202R solvent front mutation in ALK resistance. PMID- 29785090 TI - Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-beta1/Smad, nuclear factor-kappaB, and AKT signaling pathways in rats. AB - Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL.kg-1) at a dose of 200 mg.kg-1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. After Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, alpha-SMA, transforming growth factor (TGF)-beta1, p Smad 2/3, Smad 2/3, Smad4, NF-kappaB-p65, p-NF-kappaB-p65, IL-1beta, IL-6, AKT, and p-AKT were determined using Western blotting. Results: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and alpha-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-beta1, Smad4, p-Smad 2/3/Smad 2/3, p-NF-kappaB-p65/NF-kappaB p65, IL-1beta, IL-6, and p-AKT/AKT significantly decreased after the treatment. Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-beta1/Smad, NF-kappaB, and AKT signaling pathways and the reduction of extracellular matrix deposition. PMID- 29785089 TI - Schisandrin B ameliorated chondrocytes inflammation and osteoarthritis via suppression of NF-kappaB and MAPK signal pathways. AB - Introduction: Osteoarthritis (OA) is the most prevalent joint disorder in the elderly population, and inflammatory mediators like IL-1beta were thought to play central roles in its development. Schisandrin B, the main active component derived from Schisandra chinensis, exhibited anti-oxidative and antiinflammatory properties. Methods: In the present study, the protective effect and the underlying mechanism of Schisan-drin B on OA was investigated in vivo and in vitro. Results: The results showed that Schisandrin B decreased IL-1beta-induced upregulation of matrix metalloproteinase 3 (MMP3), MMP13, IL-6, and inducible nitric oxide synthase (iNOS) and increased IL-1beta-induced downregulation of collagen II, aggrecan, and sox9 as well. Schisandrin B significantly decreased IL 1beta-induced p65 phosphorylation and nuclear translocation of p65 in rat chondrocytes. Mitogen-activated protein kinase (MAPK) activation was also inhibited by Schisandrin B, as evidenced by the reduction of p38, extracellular signal-regulated kinase (Erk), and c-Jun amino-terminal kinase (Jnk) phosphorylation. In addition, Schisandrin B prevented cartilage degeneration in rat OA model with significantly lower Mankin's score than the control group. Conclusion: Our study demonstrated that Schisandrin B ameliorated chondrocytes inflammation and OA via suppression of nuclear factor-kappaB (NF-kappaB) and MAPK signal pathways, indicating a therapeutic potential in OA treatment. PMID- 29785092 TI - Patient satisfaction with care in an urban tertiary referral academic glaucoma clinic in the US. AB - Background: The purpose of this study was to determine the factors associated with glaucoma patients' satisfaction with their medical care by fellowship trained glaucoma specialists in an urban tertiary referral clinic in the US. Methods: A total of 110 established patients aged >=60 years with a diagnosis of either primary open angle glaucoma, glaucoma suspect, or ocular hypertension monitored by an ophthalmologist with fellowship training in glaucoma were enrolled at an academic, urban, tertiary referral eye clinic. Enrolled patients were administered a general demographics questionnaire along with a Patient Satisfaction Questionnaire-18 (PSQ-18), a Likert scale validated tool. The seven dimensions of patient satisfaction from the PSQ-18 were summarized for the sample overall and by the patients' age, race, employment status, education level, distance travelled from home address to clinic, and glaucoma therapy type. Two sample t-tests were used to compare group means. Spearman correlation coefficients were used to correlate satisfaction scores with peripheral vision and visual acuity function. Results: Overall, the general satisfaction scores were high (mean 4.62). Patients >=70 years of age had lower general satisfaction with their care (mean 4.5 vs 4.8, p=0.03), the interpersonal manner of their appointment (mean 4.7 vs 4.9, p=0.009), and with their time spent with their doctor (mean 4.4 vs 4.7, p=0.03) than patients aged 60-69 years. Non-European descent patients (47% African descent and 1% other of sample) were more satisfied with the time they spent with the doctor (mean 4.7 vs 4.4, p=0.04) and with the communication during the appointment (mean 4.8 vs 4.6, p=0.04) than European descent patients (52% of sample). Patients with a higher level of education (>high school degree) were less satisfied with the accessibility and convenience of the appointment (mean 4.3 vs <= high school, 4.6, p=0.02). There were no statistically significant differences in patient satisfaction based upon employment status, distance travelled to clinic, prior glaucoma therapy, or visual function. Conclusion: Overall, across all dimensions of the PSQ-18, patients were highly satisfied with the care they received at the urban tertiary care glaucoma clinic. PMID- 29785091 TI - Health-related quality of life in type 2 diabetes mellitus patients with different risk for obstructive sleep apnea. AB - Purpose: Our study primarily aimed to investigate health-related quality of life (HRQoL) in type 2 diabetes mellitus (T2DM) patients with different risk for obstructive sleep apnea (OSA). Patients and methods: This cross-sectional, questionnaire-based study included 466 adult patients with T2DM on regular visit to Center for Diabetes of University Hospital of Split from April to September 2017. All subjects underwent detailed anamnestical evaluation and physical examination with anthropometric measurements. Additionally, all subjects completed STOP (Snoring, Tiredness, Observed apnea, and high blood Pressure) questionnaire to assess risk for OSA, Epworth Sleepiness Scale to assess daytime sleepiness, and Medical Outcomes Study Short Form-36 (SF-36) instrument to evaluate HRQoL. Results: Most subjects (N=312, 67.0%) represented high-risk OSA group based on STOP questionnaire (STOP score >=2). Statistically significantly lower HRQoL scores in all SF-36 dimensions were found in T2DM patients with high risk for OSA compared to low-risk group (P<0.001). STOP score showed statistically significant negative correlation with all SF-36 dimensions (P<0.001). In multiple linear regression analysis, STOP score was confirmed as statistically significant independent predictor for all SF-36 components, adjusted for body mass index, age, glycated hemoglobin, and T2DM duration (P<0.001). Conclusion: Our study found that high proportion of patients with T2DM are at high risk for OSA. Furthermore, we showed that group of T2DM patients with high risk for OSA has lower HRQoL in all SF-36 dimensions compared to low-risk patients. PMID- 29785093 TI - Assessment of patients' warfarin knowledge and anticoagulation control at a joint physician- and pharmacist-managed clinic in China. AB - Purpose: Warfarin is a widely used anticoagulant with a narrow therapeutic index, and it requires close monitoring and adequate patient education. We aimed to assess the knowledge level regarding warfarin therapy among its users and to identify the factors that significantly influence anticoagulation control. Patients and methods: Patients attending the Warfarin Clinic at the Beijing Tiantan Hospital were enrolled in this study. Patients' knowledge on warfarin was assessed using a validated Anticoagulation Knowledge Assessment (AKA) questionnaire. Patients' responses to each question were analyzed to identify areas of improvement in current warfarin education. International normalized ratio (INR) control was defined by the time in therapeutic range (TTR) calculated using the Rosendaal method. Spearman correlation analysis was used to investigate the association between TTR and the independent variables. Results: A total of 65 patients were enrolled in this study. Eleven questions were answered correctly by <50% of the patients. A total of 858 INR results were recorded; 432 INR values (50.3%) reached the predefined goals, and the mean TTR was 49.8%+/-24.8%. There were significant associations between TTR and patients' AKA scores (R=0.356, P=0.004) and between TTR and patients' educational levels (R=0.339, P=0.006). No significant association was observed between other factors (age and duration of anticoagulation) and TTR. The INR outcome measure was positively associated with patients' knowledge on warfarin and their educational levels. Conclusion: Areas for improvement in patient education have been identified, and processes for educational modification are currently in development. PMID- 29785095 TI - Factors affecting medication adherence in community-managed patients with hypertension based on the principal component analysis: evidence from Xinjiang, China. AB - Purpose: The analysis of factors affecting the nonadherence to antihypertensive medications is important in the control of blood pressure among patients with hypertension. The purpose of this study was to assess the relationship between factors and medication adherence in Xinjiang community-managed patients with hypertension based on the principal component analysis. Patients and methods: A total of 1,916 community-managed patients with hypertension, selected randomly through a multi-stage sampling, participated in the survey. Self-designed questionnaires were used to classify the participants as either adherent or nonadherent to their medication regimen. A principal component analysis was used in order to eliminate the correlation between factors. Factors related to nonadherence were analyzed by using a chi2-test and a binary logistic regression model. Results: This study extracted nine common factors, with a cumulative variance contribution rate of 63.6%. Further analysis revealed that the following variables were significantly related to nonadherence: severity of disease, community management, diabetes, and taking traditional medications. Conclusion: Community management plays an important role in improving the patients' medication-taking behavior. Regular medication regimen instruction and better community management services through community-level have the potential to reduce nonadherence. Mild hypertensive patients should be monitored by community health care providers. PMID- 29785094 TI - Association of health literacy and medication self-efficacy with medication adherence and diabetes control. AB - Introduction: The exact pathway linking health literacy, self-efficacy, medication adherence, and glycemic control for type 2 diabetes remains unclear. Understanding the relationship between patient factors, medication adherence, and lower glycated hemoglobin (HbA1c) may help patients better manage their disease. This study examined the association of health literacy and medication self efficacy with self-reported diabetes medication adherence, and the association of health literacy, medication self-efficacy, and self-reported diabetes medication adherence with HbA1c of patients with type 2 diabetes. Methods: This cross sectional study utilized a face-to-face questionnaire at two family medicine clinics in a Midwestern state among 174 patients; subjects enrolled were at least 20 years old with diagnosed type 2 diabetes, prescribed at least one oral diabetes medicine, and understood English. Questionnaires were administered to assess the participants': health literacy, using the Newest Vital Sign six-item questionnaire (NVS); self-efficacy for medication use, using the 13-item Self Efficacy for Appropriate Medication Use Scale; and self-report medication adherence, using the eight-item Morisky Medication Adherence Scale. HbA1c values were obtained from participants' electronic medical records. Multiple linear regressions were used to explore the association of health literacy and medication self-efficacy with both medication adherence and HbA1c level after controlling for all other covariates. Results: Self-reported health status (beta = 0.17, p = 0.015) and medication self-efficacy (beta = 0.53, p < 0.001) were positively associated with diabetes medication adherence. Health literacy was neither associated with diabetes medication adherence (beta = -0.04, p = 0.586) nor HbA1c (beta = -0.06, p = 0.542). Lower diabetes medication adherence (beta = 0.26, p = 0.008) and higher number of prescribed medications (beta = 0.28, p = 0.009) were correlated with higher HbA1c. Conclusion: Health literacy, as measured by the NVS, does not correlate with medication adherence or glycemic control among patients with type 2 diabetes. Interventions to improve patients' self-efficacy of medication use may improve diabetes medication adherence. PMID- 29785097 TI - Inter-gender differences of balance indicators in persons 60-90 years of age. AB - Introduction: Precision of movements responsible for maintaining balance deteriorates with age due to natural involutionary processes, thus prompting a research question whether the values of gender-related stability indicators might differ significantly among the study subjects over 60 years of age. Methods: The study group comprised 136 seniors (89 women, 47 men; aged 60-90 years). The CQ Stab 2P 2-platform posturograph was used as the main research device, whereas the Mann-Whitney U-test was used to evaluate the gender-related differences in the average level of variables. Results: In the open-eye test, significant gender related differences were observed with regard to the statokinesiogram's path length in the mediolateral (ML) direction in the subjects aged 60-69 years (p=0.004), mean frequency of center of pressure (COP) displacement and number of COP displacements in the ML direction in the subjects aged 70-79 years (p=0.028, p=0.019), and mean COP displacement in the anteroposterior (AP) direction in the subjects aged 80-90 years (p=0.026). When the subjects were deprived of visual control, gender-related differences were observed with regard to the mean frequency of COP displacement, number of COP displacements in the ML direction in the subjects aged 60-69 years (p=0.045, p=0.049), and the statokinesiogram's path length in the AP direction in the subjects aged 70-79 years (p=0.015). In the oldest age group, the differences were noted in the statokinesiogram's path length in the AP direction (p=0.001), a sway area delimited by the COP point (p=0.003), range of AP stability (p<0.001), and range of ML stability (p=0.048). Conclusion: Gender-related differences affecting postural stability were found in the elderly. Men were characterized by a lower level of postural stability when compared with women. This highlights the need to have the gender-related differences taken into account, when developing various preventive and therapeutic programs specifically aimed at compensating certain involution dependent deficits. PMID- 29785096 TI - Smartphone apps for improving medication adherence in hypertension: patients' perspectives. AB - Purpose: Digital interventions, such as smartphone applications (apps), are becoming an increasingly common way to support medication adherence and self management in chronic conditions. It is important to investigate how patients feel about and engage with these technologies. The aim of this study was to explore patients' perspectives on smartphone apps to improve medication adherence in hypertension. Methods: This was a qualitative study based in the West of Ireland. Twenty-four patients with hypertension were purposively sampled and engaged in focus groups. Thematic analysis on the data was carried out. Results: Participants ranged in age from 50 to 83 years (M=65 years) with an equal split between men and women. Three major themes were identified in relation to patients' perspectives on smartphone apps to improve medication adherence in hypertension: "development of digital competence," "rules of engagement," and "sustainability" of these technologies. Conclusion: These data showed that patients can identify the benefits of a medication reminder and recognize that self-monitoring their blood pressure could be empowering in terms of their understanding of the condition and interactions with their general practitioners. However, the data also revealed that there are concerns about increasing health related anxiety and doubts about the sustainability of this technology over time. This suggests that the current patient perspective of smartphone apps might be best characterized by "ambivalence." PMID- 29785099 TI - Comparison of the effectiveness of complex decongestive therapy and compression bandaging as a method of treatment of lymphedema in the elderly. AB - Background: Lymphedema is a chronic condition which significantly lowers the quality of patient life, particularly among elderly populations, whose mobility and physical function are often reduced. Objectives: The aim of the study was to compare the effectiveness of multi-layer compression bandaging (MCB) and complex decongestive therapy (CDT), and to show that MCB is a cheaper, more accessible and less labor intensive method of treating lymphedema in elderly patients. Patients and methods: The study included 103 patients (85 women and 18 men) aged >=60 years, with unilateral lower limb lymphedema. The subjects were divided into two groups: 50 treated with CDT and 53 with MCB. Pre- and post-treatment BMI, and average and maximum circumference of the edematous extremities were analyzed. Results: Reduction in swelling in both groups was achieved after 15 interventions. Both therapies demonstrated similar efficacy in reducing limb volume and circumference, but MCB showed greater efficacy in reducing the maximum circumference. Conclusion: Compression bandaging is a vital component of CDT. Maximum lymphedema reduction during therapy and maintaining its effect cannot be achieved without it. It also demonstrates its effectiveness as an independent method, which can reduce therapy cost and accessibility. PMID- 29785098 TI - Sarcopenia: assessment of disease burden and strategies to improve outcomes. AB - Life expectancy is increasing worldwide, with a resultant increase in the elderly population. Aging is characterized by the progressive loss of skeletal muscle mass and strength - a phenomenon called sarcopenia. Sarcopenia has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors - in particular, nutritional status and degree of physical activity. According to the operational definition by the European Working Group on Sarcopenia in Older People (EWGSOP), the diagnosis of sarcopenia requires the presence of both low muscle mass and low muscle function, which can be defined by low muscle strength or low physical performance. Moreover, biomarkers of sarcopenia have been identified for its early detection and for a detailed identification of the main pathophysiological mechanisms involved in its development. Because sarcopenia is associated with important adverse health outcomes, such as frailty, hospitalization, and mortality, several therapeutic strategies have been identified that involve exercise training, nutritional supplementation, hormonal therapies, and novel strategies and are still under investigation. At the present time, only physical exercise has showed a positive effect in managing and preventing sarcopenia and its adverse health outcomes. Thus, further well-designed and well-conducted studies on sarcopenia are needed. PMID- 29785100 TI - Gender-specific estimates of COPD prevalence: a systematic review and meta analysis. AB - Rationale: COPD has been perceived as being a disease of older men. However, >7 million women are estimated to live with COPD in the USA alone. Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited. Objectives: To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women. Materials and methods: A systematic review and meta analysis reporting gender-specific prevalence of COPD was undertaken. Gender specific prevalence estimates were abstracted from relevant studies. Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected. A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity. Measurements and main results: Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women. Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%). Meta regression indicated that age >=40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies. Conclusion: We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review. These results will increase awareness of COPD as a critical woman's health issue. PMID- 29785101 TI - Exacerbation recovery patterns in newly diagnosed or maintenance treatment-naive patients with COPD: secondary analyses of TICARI 1 trial data. AB - Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naive patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI). Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 ug maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naive COPD patients with acute RTI symptoms for <=7 days. Patients received standard care for AECOPD and RTI. Due to under-recruitment, the trial ended early and hence was underpowered to detect treatment differences. Data were pooled and exacerbation recovery patterns examined by using the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), forced expiratory volume in 1 second, rescue medication use, COPD Assessment TestTM, Functional Assessment of Chronic Illness Therapy-Short Form, and Work Productivity and Activity Impairment Questionnaire: Respiratory Symptoms. Results: Of 140 patients, 73.6% had a prior COPD diagnosis without maintenance therapy; 80.0% had moderate-to-severe airflow obstruction. In addition to study drug, 40.0% were prescribed pharmacologic therapy (corticosteroids [34.3%], antibiotics [16.4%], and short-acting beta2-adrenergic agonists [5.0%]) within +/ 7 days of randomization. Over 12 weeks, 78.6% exhibited symptomatic recovery (EXACT score) in a median of 5.0 days. Across all patients, 49.3% recovered without relapse, 29.3% recovered and then relapsed, and 21.4% had persistent symptoms (recovery criteria unmet). Conclusion: A substantial portion of newly diagnosed or maintenance treatment-naive patients with COPD experience relapse or persistent symptoms following a clinic visit for AECOPD with symptoms of RTI. Whether initiating maintenance therapy could improve outcomes and reduce exacerbation risk requires further study. PMID- 29785102 TI - Experiences of a health coaching self-management program in patients with COPD: a qualitative content analysis. AB - Purpose: To describe the experiences of patients with COPD participating in a health coaching self-management program. Patients and methods: Twenty patients who had participated in a 6-month health coaching self-management program intervention were purposefully selected for a qualitative evaluation of the program using semi-structured interviews. The interviews were analyzed using inductive qualitative content analysis. Results: Four categories and 13 subcategories emerged describing the participants' experiences of the program. Their experiences were expressed as gaining insight into the importance of knowledge and personal responsibilities in the management of COPD, taking action to maintain a healthy lifestyle, feeling supported by the program, and being hindered by individual and program limitations. Conclusion: Iterative interactions between patients and health care professionals together with the content of the program are described as important to develop skills to manage COPD. However, in future self-management programs more awareness of individual prerequisites should be considered. PMID- 29785103 TI - Chinese version of the severe respiratory insufficiency questionnaire for patients with COPD receiving long-term oxygen therapy. AB - Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients' symptoms and increase survival. As COPD is incurable, improving patients' health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach's alpha coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach's alpha coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China. PMID- 29785104 TI - Respiratory medication used in COPD patients from seven Latin American countries: the LASSYC study. AB - Background: Limited information is available regarding medication use in COPD patients from Latin America. This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region. Methods: This was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries. Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire. The type of medication was assessed as: short-acting beta-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long acting beta-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other. Results: In total, 795 patients were included (59.6% male), with a mean age of 69.5+/-8.7 years and post-bronchodilator FEV1 of 50.0%+/-18.6%. The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%). The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%). The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire. Conclusion: COPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region. Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence. PMID- 29785105 TI - Development and blood compatibility assessment of electrospun polyvinyl alcohol blended with metallocene polyethylene and plectranthus amboinicus (PVA/mPE/PA) for bone tissue engineering. AB - Introduction: Currently, the design of extracellular matrix (ECM) with nanoscale properties in bone tissue engineering is challenging. For bone tissue engineering, the ECM must have certain properties such as being nontoxic, highly porous, and should not cause foreign body reactions. Materials and methods: In this study, the hybrid scaffold based on polyvinyl alcohol (PVA) blended with metallocene polyethylene (mPE) and plectranthus amboinicus (PA) was fabricated for bone tissue engineering via electrospinning. The fabricated hybrid nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform and infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), contact angle measurement, and atomic force microscopy (AFM). Furthermore, activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolytic assays were used to investigate the blood compatibility of the prepared hybrid nanocomposites. Results: The prepared hybrid nanocomposites showed reduced fiber diameter (238+/-45 nm) and also increased porosity (87%) with decreased pore diameter (340+/-86 nm) compared with pure PVA. The interactions between PVA, mPE, and PA were identified by the formation of the additional peaks as revealed in FTIR. Furthermore, the prepared hybrid nanocomposites showed a decreased contact angle of 51 degrees +/-1.32 degrees indicating a hydrophilic nature and exhibited lower thermal stability compared to pristine PVA. Moreover, the mechanical results revealed that the electrospun scaffold showed an improved tensile strength of 3.55+/-0.29 MPa compared with the pristine PVA (1.8+/-0.52 MPa). The prepared hybrid nanocomposites showed delayed blood clotting as noted in APTT and PT assays indicating better blood compatibility. Moreover, the hemolysis assay revealed that the hybrid nanocomposites exhibited a low hemolytic index of 0.6% compared with pure PVA, which was 1.6% suggesting the safety of the developed nanocomposite to red blood cells (RBCs). Conclusion: The prepared nanocomposites exhibited better physico-chemical properties, sufficient porosity, mechanical strength, and blood compatibility, which favors it as a valuable candidate in bone tissue engineering for repairing the bone defects. PMID- 29785106 TI - SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study. AB - Background: SN38 (7-ethyl-10-hydroxycamptothecin) is a camptothecin derivative acts against various tumors. However, SN38 is hydrolyzed in the physiological environment (pH 7.4), and this instability interferes with its potential therapeutic effect. Our objective was to investigate SN38-loaded liposomes to overcome the poor solubility of SN38 and its biodistribution, which further diminish its toxicity. Materials and methods: The sub-100 nm targeted liposomes was employed to deliver SN-38 and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay. Results: The SN38-loaded targeted liposomes consisted of small (100.49 nm) spherical nanoparticles with negative charge (-37.93 mV) and high entrapment efficiency (92.47%). The release behavior of the SN38-loaded targeted liposomes was fitted with Higuchi kinetics (R2=0.9860). Free SN38 presented initial burst release. The IC50 for the SN38-loaded targeted liposomes (0.11 MUM) was significantly lower than for the SN38 solution (0.37 MUM) in the MCF7 cell line (P<0.01). Confocal laser scanning microscopy also confirmed highly efficient accumulation in the MCF7 cells. Pharmacokinetics demonstrated that the SN38-loaded targeted liposomes had a slightly increased half-life and mean residence time and decreased area under the concentration-time curve and maximum concentration. The results suggested that retention was achieved while the exposure of SN38 was significantly decreased. A noninvasive in vivo imaging system also showed that the targeted liposomes selectively targeted MCF7 tumors. In vivo toxicity data demonstrated that the decrease in platelets was significantly improved by SN38 loaded targeted liposomes, and diarrhea was not observed in BALB/c mice. Conclusion: In summary, SN38-loaded targeted liposomes could be a good candidate for application in human breast cancer. PMID- 29785107 TI - Near-infrared light-mediated photodynamic/photothermal therapy nanoplatform by the assembly of Fe3O4 carbon dots with graphitic black phosphorus quantum dots. AB - Background: Recently, combined photodynamic therapy (PDT) and photothermal therapy (PTT) has become a desired treatment for cancer. However, the development of economic, high-efficiency, and safe photosensitizers/photothermal agents remains a significant challenge. Methods: A novel nanocomposite has been developed via the assembly of iron oxide carbon dot (Fe3O4-CDs) nanoparticles and black phosphorus quantum dots (genipin [GP]-polyglutamic acid [PGA]-Fe3O4 CDs@BPQDs), and this nanocomposite shows a broad light-absorption band and a photodegradable character. Results: In vitro and in vivo assays indicated that GP PGA-Fe3O4-CDs@BPQDs were highly biocompatible and exhibited excellent tumor inhibition efficacy, due to the synergistic PTT and PDT via a near-infrared laser. Importantly, in vivo tumor magnetic resonance imaging (MRI) results illustrated that GP-PGA-Fe3O4-CDs@BPQDs can be specifically applied for enhanced T2 MRI of tumors. This work presents the first combined application of a PDT and PTT effect deriving from BPQDs and MRI from Fe3O4-CDs, which may promote utilization of black BPQDs in biomedicine. Conclusion: As expected, GP-PGA-Fe3O4 CDs@BPQDs displayed a dramatically enhanced ability to destroy tumor cells, due to the synergistic combination of PTT and PDT. PMID- 29785108 TI - The protective role of quercetin and arginine on gold nanoparticles induced hepatotoxicity in rats. AB - Background: The aim of the study was to confirm the hepatotoxicity induced by small-sized gold nanoparticles (GNPs) and evaluate the role of quercetin (Qur) and arginine (Arg) against hepatotoxicity caused by GNPs. Methods: Twenty-five healthy male Wistar-Kyoto rats were used. GNPs were administered intraperitoneally to these rats at the dose of 50 MUL for seven consecutive days. The role of Qur and Arg antioxidants against toxicity induced by GNPs was detected through the measurement of serum liver function and oxidative stress biomarkers in the liver tissues. Results: Coadministration of Qur and Arg along with GNPs significantly induced dramatic alterations in the biochemical parameters. Levels of malondialdehyde, gamma-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and total protein increased significantly in the GNPs injected group than in the control group, while reduced glutathione was greatly reduced in the GNPs group than in the control group. It also significantly decreased liver enzymes and the oxidative stress, therefore improving the liver damage and hepatotoxicity induced by GNPs. Conclusion: This study demonstrated that Qur and Arg antioxidants effectively improved the hepatic oxidative damage induced by GNPs. It also substantiates the application of Qur and Arg as protecting stand-in against GNPs' hepatotoxicity. PMID- 29785109 TI - Development and characterization of a nanoemulsion containing propranolol for topical delivery. AB - Background: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo. Methods: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m. Results: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of -20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay. Conclusion: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas. PMID- 29785110 TI - Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies. AB - Objective: Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas. Methods: We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified. Results: Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger's tests further confirmed these findings. Conclusions: Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder. PMID- 29785112 TI - Treatment of behavioral and psychological symptoms of dementias with psychopharmaceuticals: a review. AB - Behavioral and psychological symptoms represent common complications in patients with different types of dementia. Predominantly, they comprise psychosis, agitation and mood disorders, disinhibited behavior, impairment of the sleep and wakefulness rhythm, wandering, perseveration, pathological collecting, or shouting. Their appearance is related to more rapid progression of the disease, earlier institutionalization, use of physical restraints, and higher risk of mortality. Consequently, appearance of behavioral and psychological symptoms of dementia leads to higher costs of care provided and greater distress for caregivers. Clinical guidelines recommend nonpharmacological approaches as the first choice in the treatment of behavioral and psychological symptoms. Pharmacological therapy should be initiated only if the symptoms were not the result of somatic causes, did not respond to nonpharmacological interventions, or were not caused by the prior medication. Acetylcholinesterase inhibitors, memantine, antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines are used. This review summarizes the current findings about the efficacy and safety of the treatment of the neuropsychiatric symptoms in dementias with psychopharmaceuticals. Recommendations for treatment with antipsychotics for this indication are described in detail as this drug group is prescribed most often and, at the same time, is related to the highest risk of adverse effects and increased mortality. PMID- 29785111 TI - Association of serotonin receptor 2a haplotypes with obsessive-compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study. AB - Introduction: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%-60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Patients and methods: Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300 mg). Treatment response was considered as >25% reduction in Yale-Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. Results: The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311-rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. Conclusion: HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation. PMID- 29785114 TI - Convenient food made of extruded adzuki bean attenuates inflammation and improves glycemic control in patients with type 2 diabetes: a randomized controlled trial. AB - Objective: Extrusion is a widely used food processing technology. The aim of this study was to investigate the effects of extruded adzuki bean convenient food (EABCF) on glycemic and inflammation control in type 2 diabetes mellitus (T2DM) patients. Patients and methods: In a randomized controlled trial, 120 T2DM patients were randomly assigned to a control diet group (the low glycemic index [LGI] group, assigned the traditional diabetic low glycemic index diet) or an intervention group (the EABCF group, assigned daily consumption of EABCF). Diet information and blood samples were collected at baseline and after a 4-week intervention. After excluding exogenous insulin users, a subgroup analysis based on baseline fasting insulin (FINS) levels was conducted, and Homeostasis Model Assessment (HOMA) was the target indicator. Results: A total of 106 patients completed the trial, and 89 participants were included in the subgroup analysis. After the intervention, glycemic control improved in both groups compared to baseline, but the difference was not statistically significant (p>0.05). However, the EABCF group showed decreased inflammation with significantly lower tumor necrosis factor alpha (TNF-alpha) level compared to the control group (adjusted p<0.01). There was also a slight increase in the interleukin-6 (IL-6) level in the EABCF group (adjusted p=0.004). Moreover, the subgroup analysis found that, after 4 weeks, a diet consisting of EABCF increased insulin secretion to normal levels in the group with hypoinsulinism (baseline FINS<5.2 mU/L). However, the difference only showed a trend toward statistical significance (0.05A, rs3790844 T>C, rs12029406 C>T) are associated with the risk of pancreatic cancer. However, the results of epidemiological investigations are still controversial. In order to explore its potential attributing factors, we pooled the updated literatures to evaluate the association between NR5A2 polymorphism and the risk of pancreatic cancer in this meta-analysis. Materials and methods: Databases such as PubMed, Google Scholar and China National Knowledge Infrastructure were searched for eligible articles following strict inclusion and exclusion criteria (updated to November 18, 2017). Odds ratios (ORs) and 95% CIs were computed to assess the intensity of association. In addition, heterogeneity, sensitivity analysis and publication bias were explored. All statistical analyses were conducted by STATA 14.0. Results: Our results showed that the rs3790843 (GA vs GG: OR=0.86, CI=0.76-0.98, P=0.992; GA+AA vs GG: OR=0.83, CI=0.73-0.94, P=0.950; A vs G: OR=0.85, CI=0.78 0.93, P=0.802), rs3790844 (CC vs TT: OR=0.65, CI=0.54-0.78, P=0.617; CC vs TT+CT: OR=0.73, CI=0.62-0.85, P=0.742; C vs T: OR=0.78, CI=0.73-0.84, P=0.555) and rs12029406 (TT vs CC: OR=0.73, CI=0.61-0.89, P=0.483; TT vs CC+CT: OR=0.78, CI=0.66-0.92, P=0.648; T vs C: OR=0.87, CI=0.79-0.95, P=0.837) polymorphisms were associated statistically with the risk of pancreatic cancer. Furthermore, the results of subgroup analysis showed that rs3790843 and rs3790844 polymorphisms were especially related to the risk of pancreatic cancer in Caucasian population. Conclusion: Our results revealed that NR5A2 may have a protective effect on pancreatic cancer. However, more well-designed researches are needed to verify the relationship between NR5A2 polymorphisms and the risk of pancreatic cancer. PMID- 29785121 TI - Association between angiogenesis and cytotoxic signatures in the tumor microenvironment of gastric cancer. AB - Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer. Materials and methods: Transcriptome profiling data retrieved from The Cancer Genome Atlas (TCGA) database were used to deconvolute the feature of TME for gastric cancer (N = 375). Machine learning, correlation, and prognosis analysis were applied to elucidate the correlations between angiogenesis, cytotoxic T lymphocyte infiltration, and patient survival. Results: Substantial heterogeneous infiltration of immune cell populations among cases was observed. Furthermore, among targetable pathways, angiogenesis was identified as the dominant factor in discriminating different infiltration statuses. Most importantly, the angiogenesis pathway was negatively correlated with the amount of activated CD8+ T cells only for patients with a higher infiltration, and the concomitance of low angiogenesis signaling and highly activated CD8+ T-cell infiltration was associated with a significant survival benefit. Conclusion: Our findings demonstrated a negative correlation between angiogenesis signaling and cytotoxic function in gastric cancer patients with a highly infiltrated immune niche. These data provided a rationale for potential combination strategy and further clinical investigations of ICIs plus antiangiogenesis agents for patients with gastric cancer with an inflamed TME. PMID- 29785122 TI - Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in prostate cancer in vitro and in vivo. AB - Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated. Methods: PCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells. Results: ALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells. Conclusion: Based on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa. PMID- 29785123 TI - Leucine-rich alpha-2-glycoprotein-1 is up-regulated in colorectal cancer and is a tumor promoter. AB - Background: Leucine-rich alpha-2-glycoprotein-1 (LRG1) is differentially expressed in many kinds of diseases including cancer, however, it has not been thoroughly studied yet. Purpose: The objective of this study was to detect the expression and potential mechanism of LRG1 in colorectal cancer (CRC). In our study, we examined LRG1 levels in CRC tissue and plasma with quantitative real time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of LRG1 on cancer cells was detected with transwell and MTT assays. Results: The average plasma LRG1 level in CRC was significantly higher than in polyp group (P=0.002) and healthy controls (P<0.001). Second, plasma LRG1 was positively associated with CA19-9 (r=0.133, P=0.039) and neutrophil ratio (r=0.403, P<0.001). Third, plasma LRG1 of stage IV patients was dramatically different from that of stage I, stage II or stage III patients (P<0.001). LRG1 mRNA expression levels were about 2-fold higher in CRCs compared to normal tissues (P<0.001). And levels of plasma LRG1 were found to be a risk factor in CRC in univariate survival analysis of colorectal prognosis (P=0.013, hazard ratio [HR]=1.803, 95% CI: 1.521-2.137), and multivariate analysis showed that LRG1 was an independent risk factor (P<0.001, HR=1.492, 95% CI: 1.223 1.820). The patients with higher plasma LRG1 value presented with poorer outcome (P=0.013). Functional experiments showed that LRG1 could promote the invasion and growth ability of cells. LRG1 was increased in plasma and tissue compared with that of controls and LRG1 may predict prognosis of CRC patients and LRG1 maybe a tumor promoter. Conclusion: LRG1 is increased in CRC patients and might serve as a tumor promoter. PMID- 29785124 TI - Upregulation of circ_0066444 promotes the proliferation, invasion, and migration of gastric cancer cells. AB - Background: Circular RNAs (circRNAs), which have closed-loop structure, are involved in the pathogenesis of human diseases including various types of carcinomas. The present study aimed to investigate the relationship between a new circular RNA named circ_0066444 and gastric cancer (GC) carcinogenesis. Materials and methods: The circ_0066444 levels in 106 paired gastric carcinoma tissues and related adjacent normal tissues were detected by real-time quantitative reverse transcription polymerase chain reaction. The correlation between the expression of circ_0066444 and clinicopathological features was analyzed. The impact of circ_0066444 expression on cell proliferation, invasion, as well as migration was evaluated in vitro using knockdown expression strategies. Finally, a network of circ_0066444-targeted miRNA interactions and their corresponding mRNAs was constructed. Results: circ_0066444 was found to be significantly upregulated in 106 GC tissues as compared with paired adjacent nontumorous tissues (P=0.025), showing a high positive correlation with lymphatic metastasis (P=0.023). Furthermore, in vitro assays of the GC cell lines BGC-823 and AGS demonstrated that knockdown of circ_0066444 reduced cell proliferation, invasion, and migration significantly. Prediction and annotation revealed circ_0066444 was able to sponge to 5 miRNAs and 15 corresponding target mRNAs. Conclusion: Our study indicated upregulation of circ_0066444 promotes gastric cell proliferation, invasion, and migration ability and might serve as a novel biomarker for GC. PMID- 29785125 TI - ZNF418 overexpression protects against gastric carcinoma and prompts a good prognosis. AB - Background: This study aimed to investigate the prognostic power of zinc-finger protein 418 (ZNF418) in gastric cancer (GC) and its potential role in GC development and progression. Patients and methods: A total of 10 GC patients' individual plasmas were collected and screened for dysregulated mRNA using human microarray. Among these dysregulated mRNAs, ZNF418 was found to be significantly downregulated in IIIA-IV stage GC patients compared to IA-IIA stage GC patients. Subsequently, the ZNF418 levels were detected by quantitative reverse transcription-polymerase chain reaction in both GC plasmas and tissues in a larger sample, and the association between ZNF418 expression level and clinicopathological features as well as overall survival (OS) of GC patients was further analyzed. Finally, a network of ZNF418 interactions with other molecules was predicated in STRING and GEPIA databases. Results: Human mRNA microarray was performed to screen for abnormally expressed mRNAs between five IIIA-IV stage GC patients' plasma and five IA-IIA stage GC patients' plasma. A total of 662 mRNAs were differentially expressed in the IIIA-IV stage GC plasma vs IA-IIA stage GC plasma among all the candidate mRNAs according to the Student's t-test. Results showed that a decrease in the ZNF418 expression level was associated with the presence of GC and also with higher tumor-node-metastasis stage and lower OS rates compared with that in adjacent noncancerous tissues. Cox regression analysis results demonstrated that the OS was independently correlated with ZNF418 expression. Finally, the prediction results showed that a total of eight mRNAs might have an interaction with ZNF418 in both STRING and GEPIA databases. Conclusion: ZNF418 was first identified to be significantly downregulated in GC. Our study indicated that ZNF418 might serve as a novel biomarker for GC and was involved in GC development. PMID- 29785126 TI - Impact of targeting transforming growth factor beta-2 with antisense OT-101 on the cytokine and chemokine profile in patients with advanced pancreatic cancer. AB - Background: Overexpression of the cytokine - transforming growth factor-beta 2 (TGF-beta2) - has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-beta2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-beta receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC. Materials and methods: Plasma levels of 31 cyto-/chemokines were tracked over three cycles of OT-101 therapy (140 mg/m2/day) in 12 PAC patients. Samples were acquired before onset of OT-101 therapy and at eight selected time points during therapy. A mixed ANCOVA model was developed for 19 cyto-/chemokines with median expression >1 following OT-101 therapy. Regression and hierarchical clustering analyses were performed to identify correlated expressions in each patient across cyto-/chemokines or in each cyto-/chemokine across patients. Plasma cyto /chemokine levels were compared with OS with and without subsequent chemotherapy. Results: Three highly correlated subsets of cyto-/chemokines (Cluster 1: EGF, MIP 1alpha, MIP-1beta; Cluster 2: FGF-2, MIG, IP-10, IL-15, IFN-alpha, IL-12; and Cluster 3: HGF, IL-6, IL-8) were identified following OT-101 therapy. Suppression of TGF-beta signaling by OT-101 led to upregulation of IL-8, IL-15, IP-10, and HGF. Protein-protein interaction networks constructed using STRING10 algorithm identified a relationship between IL-8, IL-15, and TGF-beta receptor type 2 inhibition. The mixed analysis of covariance model that examined the levels of 19 cyto-/chemokines with OS as the covariate at each of the time points resulted in IL-8 and IL-15 exhibiting a significant association with OS during Cycle 1 of therapy. In the whole-blood culture model, the cytokines with the most pronounced increase after OT-101 treatment were IL-1beta, IL-8, and MCP-1. Conclusion: No consistent responses in cyto-/chemokine levels were observed due to OT-101 treatment. Levels of IL-8 and IL-15 during Cycle 1 were positively associated with OS across 12 patients with PAC and served as potential biomarkers for treatment outcome following OT-101 therapy. PMID- 29785127 TI - Long noncoding RNA GAPLINC promotes gastric cancer cell proliferation by acting as a molecular sponge of miR-378 to modulate MAPK1 expression. AB - Background: Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. LncRNA GAPLINC has been reported to be increased in gastric cancer (GC) tissues. Methods: Real-time PCR assays were used to measure expressions of GAPLINC, miR-378, and MAPK1 mRNA. Western blot assays were employed to examine MAPK1 protein expression. Cell proliferation and cell cycle were measured by CCK-8 and propidium iodide detection assays, respectively. The interaction between GAPLINC and miR-378 was confirmed by site-directed mutagenesis and luciferase assays. Luciferase assays were also used to study whether GAPLINC was able to act as a molecular sponge of miR-378 to modulate MAPK1 expression. Results: The lncRNA GAPLINC expression was upregulated and positively correlated with MAPK1 expression in gastric cancer tissues and cells. Additionally, lncRNA GAPLINC promoted the expression of MAPK1 and the enhancement of GC cell proliferation and cell cycle progression by LncRNA GAPLINC was dependent on MAPK1 in vitro and in vivo. Consequently, we found that miR-378 expression was inversely correlated with GAPLINC expression in GC tissues and cells. miR-378 could directly bind to GAPLINC and decreased GAPLINC expression, thus reducing MAPK1 expression. Furthermore, overexpression of miR 378 inhibited MAPK1 expression, cell proliferation, and cell cycle progression of gastric cancer cells, while these effects were abrogated by upregulating lncRNA GAPLINC expression. Conclusion: Taken together, lncRNA GAPLINC promotes gastric cancer cell proliferation by acting as a molecular sponge of miR-378 to modulate MAPK1 expression. PMID- 29785128 TI - Methacholine challenge testing: comparative pharmacology. AB - Standardization of the methacholine inhalation challenge, the most common direct bronchoprovocation test, is important. One aspect of standardization is the appropriate washout period for pharmacologic agents which affect the response. This review summarizes the available data on pharmacologic inhibition of the methacholine response. Specific (anti-muscarinic) agents demonstrate marked bronchoprotection (up to 7 days for the long-acting drugs) which lasts longer than the duration of bronchodilation. The functional antagonist (beta 2 agonist class of medications) shows marked, but less, bronchoprotection which is relatively short lived and is similar to the duration of bronchodilator efficacy. Tolerance develops quickly, especially to the long-acting agents. Single doses of controller medications, such as inhaled corticosteroids (ICS) and leukotriene receptor antagonists, have no effect on the methacholine test, while regular use, at least for ICS, has a modest protective effect whose duration is uncertain and likely variable. Theophylline has a small effect and H1 blockers (all generations) have a negligible effect. PMID- 29785129 TI - Performance of the Abbott RealTime MTB RIF/INH resistance assay when used to test Mycobacterium tuberculosis specimens from Bangladesh. AB - Introduction: The Abbott RealTime MTB RIF/INH Resistance Assay (RT MTB RIF/INH) is an assay for the detection of rifampicin (RIF)- and/or isoniazid (INH) resistant Mycobacterium tuberculosis (MTB). The assay can be used to test sputum, bronchial alveolar lavage, and N-Acetyl-L-Cysteine (NALC)/NaOH pellets prepared from these samples. The assay can be used in direct testing mode, or in reflex mode following a MTB positive result produced by its companion assay, Abbott RT MTB. Methods: In this study, the direct testing mode was used to test paired sputum and NALC/NaOH pellets prepared from sputum collected from Bangladesh TB patients. One hundred and thirty two paired samples were tested. Results: The RT MTB RIF/INH inhibition rate was 0%. One hundred and twenty-two paired samples had results above the assay limit of detection and were analyzed by comparing with results from phenotypic drug sensitivity testing, GeneXpert MTB/RIF (Xpert), and MTBDR plus (Hain). RT MTB RIF/INH results were in good agreement with those of GeneXpert and Hain. Conclusion: The ability of this assay to detect RIF and INH resistance may contribute to the global control of multidrug resistant tuberculosis. PMID- 29785130 TI - Human herpesvirus-6 pneumonitis in a patient with follicular lymphoma following immunochemotherapy with rituximab. AB - Primary infection with human herpesvirus-6 (HHV-6) commonly occurs at an early age in children, most often at 3 years of age, and is associated with childhood diseases, such as exanthema subitum, hepatitis, febrile convulsions, or encephalitis. However, the virus occasionally reactivates from its latent state in immunosuppressed adults, especially post-transplant, resulting in serious disseminated, sometimes life-threatening end-organ complications. Herein, we report a case of a 68-year-old man with relapsed follicular lymphoma who developed HHV-6 pneumonitis. Eighteen months after achieving second complete remission by salvage immunochemotherapy with rituximab, the patient was complicated by pneumonia, with chest computed tomography finding showing disseminated nodular shadows with ground-glass opacity in both lungs. While empiric antibiotic and antifungal therapies did not improve the pneumonia, polymerase chain reaction-based viral screening tests on his bronchoalveolar lavage fluid detected the presence of HHV-6 DNA, and ganciclovir treatment quickly resolved the pneumonia, indicating that he suffered from HHV-6 pneumonitis. He had no other HHV-6-related end-organ damage, such as encephalitis. This case suggests that, although extremely rare, HHV-6 reactivation should be considered as one of the candidate pathogens for pulmonary complications of uncertain etiology in patients who have been treated with intensive immunosuppressive chemotherapy, even without hematopoietic stem cell transplantation. Furthermore, polymerase chain reaction-based viral screening testing on bronchoalveolar lavage fluid is a powerful diagnostic tool for pneumonitis due to viral reactivation, including HHV-6 reactivation. PMID- 29785131 TI - Epidemiology, susceptibility, and risk factors for acquisition of MDR/XDR Gram negative bacteria among kidney transplant recipients with urinary tract infections. AB - Background: Multiple drug resistant/extensively drug resistant (MDR/XDR) Gram negative urinary tract infections (UTIs) represent a growing threat to kidney transplant recipients. This retrospective study aimed to assess the incidence and microbiological profile of MDR/XDR Gram-negative UTIs, to identify drug susceptibility of MDR/XDR bacteria, and to determine the potential risk factors for MDR/XDR UTIs in kidney recipients. Materials and methods: During the study period, 1569 patients underwent consecutive kidney transplantation in two transplantation centers. We studied the demographics, clinical characteristics, and urine culture data from kidney recipients with MDR/XDR Gram-negative UTIs, and verified the risk factors associated with MDR/XDR infections. Results: Eighty one kidney recipients yielded 88 episodes of MDR/XDR Gram-negative UTIs with five patients (6.2%) succumbing to all-cause in-hospital mortality. The most frequently isolated bacterium was Escherichia coli (62.5%). Almost all MDR/XDR Gram-negative bacteria were resistant to first- and second-generation cephalosporin, and monocyclic beta-lactam. They were relatively sensitive to meropenem, amikacin, and tigecycline. As for the 12 XDR bacteria, all of them were resistant to meropenem and 25% of them were resistant to tigecycline. All XDR Acinetobacter baumannii and E. coli were susceptible to tigecycline. Nosocomial infection (odds ratio [OR] = 11.429, 95% CI = 1.311-99.625, P = 0.027) was the only independent predictor of MDR/XDR Gram-negative UTIs. Non-fermenting bacterial infection (OR = 20.161, 95% CI = 3.409-119.240, P = 0.001), polycystic kidney disease (OR = 39.871, 95% CI = 1.979-803.384, P = 0.016), and serum creatinine level > 1.5 mg/dL (OR = 8.688, 95% CI = 1.354-55.747, P = 0.023) were significantly different between XDR and MDR Gram-negative UTIs. Conclusion: Meropenem, amikacin, and/or tigecycline can be prescribed for MDR/XDR Gram negative infections. Tigecycline can also be prescribed for XDR A. baumannii and E. coli. Nosocomial infection was a risk factor for MDR/XDR Gram-negative UTIs, while XDR UTIs were associated with non-fermenting bacterial infection, polycystic kidney disease, and impaired renal function. PMID- 29785132 TI - Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFalpha levels, and food intake of women with morbid obesity. AB - Background: The fat mass and obesity-related (FTO) gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation. Objective: The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6), tumor necrosis factor alpha (TNFalpha) levels and food intake of morbidly obese women. Materials and methods: The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m2. Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction. Results: Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFalpha intragenotypes, it was observed that those with TT had decreased leptin and increased IL6 at the postprandial period. Subjects with TA showed increased postprandial IL6, and those with AA had decreased postprandial ghrelin. There was no difference in TNFalpha intra- and intergenotypes. The postprandial sensations of hunger were lower in AA than those with TT. There were differences between genotypes regarding ingested grams of protein by weight, cholesterol, B3, B5, B6 and B12 vitamins, and selenium potassium and sodium minerals. Conclusion: These findings suggest that genetics may exert an influence on physiologic factors and might alter eating behavior. PMID- 29785133 TI - Are quantitative histopathologic criteria capable of differentiating psoriasis from chronic dermatitis? AB - Background: There are overlapping features in histopathologic characteristics of psoriasis and chronic dermatitis, which sometimes make the correct diagnosis difficult. Objective: The aim of this study was to compare the histopathologic diagnostic features of psoriasis with chronic dermatitis quantitatively. Patients and methods: In this study, 30 patients with psoriasis and 30 patients with chronic dermatitis were included. Diagnosis of psoriasis or chronic dermatitis was based on clinicopathologic correlation. Photos of histopathologic slides were provided by LABOMED Digital Camera and LABOMED Microscope. Width and length of rete ridges, minimal thickness of suprapapillary plates, thickness of epidermis, thickness of hyperkeratotic layer, and minimal thickness of granular layer were determined using Pixel Pro software on micrometer scale. Results: Suprapapillary plates and granular layer were significantly thicker in patients with chronic dermatitis compared with patients with psoriasis. The rete ridges were longer and wider, the epidermis was thicker, and the parakeratotic layer was also thicker in patients with psoriasis compared with patients with chronic dermatitis, and the difference between these corresponding parameters in the two groups was statistically significant except for thickness of parakeratotic layer. Moreover, the mean ratio of minimal suprapapillary plate's thickness to epidermal thickness and the mean ratio of minimal granular layer's thickness to parakeratotic layer's thickness were significantly higher in patients with chronic dermatitis compared with those with psoriasis. Conclusion: Despite overlapping histopathologic features in psoriasis and chronic dermatitis, quantitative histopathologic criteria might be valuable for differentiation of these two conditions. Ratios of minimal suprapapillary plate's thickness to epidermal thickness and minimal granular layer's thickness to parakeratotic layer's thickness can be particularly helpful in this regard. PMID- 29785134 TI - The impact of acne and facial post-inflammatory hyperpigmentation on quality of life and self-esteem of newly admitted Nigerian undergraduates. AB - Background: Acne and facial post-inflammatory hyperpigmentation are relatively common clinical conditions among adolescents and young adults, and inflict psychosocial injuries on sufferers. Objective: To document the psychosocial and self-esteem implications of acne and facial hyperpigmentation on newly admitted undergraduates. Materials and methods: A cross-sectional survey was conducted among 200 undergraduates. Demographics and clinical characteristics were obtained and acne was graded using the US Food and Drug Administration 5-category global system of acne classification. Participants completed the Cardiff Acne Disability Index (CADI) and the Rosenberg self-esteem scale (RSES), and data were analyzed using SPSS 20. Results: Mean age of acne onset was 16.24 +/- 3.32 years. There were 168 (84.0%) cases categorized as almost clear, 24 (12.0%) as mild acne, 4 (2.0%) as moderate acne and 4 (2.0%) as severe acne. Acne with facial hyperpigmentation, compared to acne without hyperpigmentation, was associated with significant level of anxiety in 30 participants (26.5% vs 10.3%, p=0.004) and emotional distress in 40 (35.4% vs 10.3%, p<0.001). Acne severity correlated with total CADI score but not with total RSES score. Quality of life (QoL) was significantly reduced among acne patients with facial hyperpigmentation (1.77+/ 1.62, vs 1.07+/-1.02, p<0.001) compared to those without hyperpigmentation. Acne and facial hyperpigmentation was associated with social life interference, avoidance of public facilities, poor body image and self-esteem and perception of worse disease. There was no association between gender and QoL but acne was related to a reduction of self-worth. Low self-esteem was present in 1.5%, and severe acne was associated with an occasional feeling of uselessness in the male gender. Conclusion: Acne with facial hyperpigmentation induces poorer QoL and self-esteem is impaired only in severe acne. Beyond the medical treatment of acne, dermatologists should routinely assess the QoL and give attention to treatment of facial post-inflammatory hyperpigmentation among people of color. PMID- 29785135 TI - Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. AB - Background: Germline mutations BRCA1 and BRCA2 contribute almost equally in the causation of breast cancer (BC). The type of mutations in the Indian population that cause this condition is largely unknown. Purpose: In this cohort, 79 randomized BC patients were screened for various types of BRCA1 and BRCA2 mutations including frameshift, nonsense, missense, in-frame and splice site types. Materials and methods: The purified extracted DNA of each referral patient was subjected to Sanger gene sequencing using Codon Code Analyzer and Mutation Surveyor and next-generation sequencing (NGS) methods with Ion torrent software, after appropriate care. Results: The data revealed that 35 cases were positive for BRCA1 or BRCA2 (35/79: 44.3%). BRCA2 mutations were higher (52.4%) than BRCA1 mutations (47.6%). Five novel mutations detected in this study were p.pro163 frameshift, p.asn997 frameshift, p.ser148 frameshift and two splice site single nucleotide polymorphisms (SNPs). Additionally, four nonsense and one in-frame deletion were identified, which all seemed to be pathogenic. Polymorphic SNPs contributed the highest percentage of mutations (72/82: 87.8%) and contributed to pathogenic, likely pathogenic, likely benign, benign and variant of unknown significance (VUS). Young age groups (20-60 years) had a high frequency of germline mutations (62/82;75.6%) in the Indian population. Conclusion: This study suggested that polymorphic SNPs contributed a high percentage of mutations along with five novel types. Younger age groups are prone to having BC with a higher mutational rate. Furthermore, the SNPs detected in exons 10, 11 and 16 of BRCA1 and BRCA2 were higher than those in other exons 2, 3 and 9 polymorphic sites in two germline genes. These may be contributory for BC although missense types are known to be susceptible for cancer depending on the type of amino acid replaced in the protein and associated with pathologic events. Accordingly, appropriate counseling and treatment may be suggested. PMID- 29785136 TI - Psychological factors as predictors of early postoperative pain after open nephrectomy. AB - Purpose: There is an increasing interest in the identification of predictors for individual responses to analgesics and surgical pain. In this study, we aimed to determine psychological factors that might contribute to this response. We hence investigated patients undergoing a standardized surgical intervention (open nephrectomy). Patients and methods: Between May 2014 and April 2015, we conducted a prospective observational cohort study. The following psychological tests were administered preoperatively: Mini-Mental State Examination, Amsterdam Preoperative Anxiety and Information Scale (APAIS), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Pain Catastrophizing Scale. The primary outcome, postoperative pain intensity (11-point numerical rating scale, [NRS]), was assessed in the "immediate early" (first 8 hours), "early" (12 and 24 hours), and "late early" periods (48 and 72 hours). Results: A total of 196 patients were assessed, and 150 were finally included in the study. NRS scores improved from 4.9 (95% confidence interval [CI]: 4.7-5.1) in the "immediate early" to 3.1 (95% CI: 2.9-3.3) in the "early" and 2.3 (95% CI: 2.1-2.5) in the "late early" postoperative period. Most (87%) patients received intravenous opioids, while 13% received analgesics epidurally. Repeated measures analysis of variance indicated better pain management with epidural analgesia in the first two postoperative periods (F=15.01, p<0.00). Postoperative pain correlated strongly with analgesic strategy and preoperative psychological assessment. Multiple linear regression analysis showed "expected pain" was the only predictor in the "immediate early" phase, and "anxiety" was most important in the "early" postoperative period. In the "late early" phase, catastrophizing was the predominant predictor, alongside "preoperative analgesic usage" and "APAIS anxiety". Conclusion: After open nephrectomy, epidural analgesia conveys a clear advantage for pain management only within the first 24 hours. Moreover, as the psychological phenotype of patients changes distinctively in the first 72 postoperative hours, psychological variables increasingly determine pain intensity, even surpassing employed analgesic strategy as its main predictor. PMID- 29785137 TI - Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway. AB - Background: Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. Materials and methods: U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways. Results: Both TP and andrographolide showed an antiproliferative effect in a dose dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression. Conclusion: The pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately. PMID- 29785139 TI - Blockage of store-operated Ca2+ entry antagonizes Epstein-Barr virus-promoted angiogenesis by inhibiting Ca2+ signaling-regulated VEGF production in nasopharyngeal carcinoma. AB - Background: Epstein-Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF mediated angiogenesis remains to be further clarified. Materials and methods: Two EBV-infected NPC cell lines, CNE2-EBV and HK1-EBV, along with their parental cell lines were employed in the present study. Dynamic cytosolic Ca2+ changes were measured in individual fluorescent Ca2+ indicator-loaded cells. Amounts of VEGF production were determined by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs)-formed tube networks were quantitatively evaluated as an in vitro angiogenesis assay. A mouse model concurrently bearing EBV-positive/negative xenografts was utilized to evaluate the tumor growth and angiogenesis in vivo. Results: EBV infection reliably promoted transplanted tumor growth while enhancing angiogenesis. Introduction of EBV into EBV-negative NPC cells increased the EGF-stimulated VEGF production while amplifying the EGF-evoked Ca2+ responses. Inhibition of the EBV-boosted Ca2+ signaling using 2-aminoethyl diphenylborinate (2-APB), a specific SOCE inhibitor, effectively antagonized the EBV-promoted VEGF production and endothelial tube formation in vitro. Pharmacological blockage of SOCE exhibited anti-angiogenic effect in the EBV-positive xenografts. Conclusion: SOCE can serve as a candidate pharmacological target for treating NPC, as blockage of the Ca2+ signaling via SOCE is a feasible strategy to suppress the EBV-driven malignant profiles in NPC cells. PMID- 29785140 TI - Do additional cores from cancer-suspicious lesions on transrectal ultrasound improve prostate cancer detection including index tumors over 12-core systematic biopsy? AB - Objective: The efficacy of additional cores from cancer-suspicious lesions by transrectal ultrasound (TRUS) for the detection of prostate cancer (PCa) was assessed. Materials and methods: Data were collected from 4144 men who underwent systematic 12-core biopsy with no cancer-suspicious lesions (Group A: 3256 cases) or 13- or more-core (systematic 12 core + additional cores) biopsy with cancer suspicious lesions (Group B: 888 cases) on TRUS-guided biopsy. The effect of additional biopsy cores on the cancer detection rate was investigated. Results: PCa was detected in 1006 (30.9%) cases in Group A and 485 (54.6%) cases in Group B (p < 0.001). In 370/485 (76.3%) patients in Group B, cancer was detected from the additional cores from TRUS suspicious lesions. Logistic regression analysis showed that the number of biopsy cores was the most significant factor for cancer detection (hazards ratio: 2.6 [2.221-3.043], p < 0.001]. Additional core biopsies did not increase the detection rate of index tumors (p < 0.001). However, the Gleason score of index tumors was higher than that of systematic cores (p < 0.001). Kaplan-Meier analysis showed no significant differences in survival according to biopsy number and location of index tumors (log-rank test: p = 0.583, p = 0.165, respectively). Conclusion: Although additional core biopsies can increase the cancer detection rate, they do not increase the detection rate of index tumors. Biopsy core number and the location of index tumors had no effect on biochemical outcomes. PMID- 29785138 TI - A review of soft-tissue sarcomas: translation of biological advances into treatment measures. AB - Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas - liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing's sarcoma, and synovial sarcoma - with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. PMID- 29785142 TI - Misoprostol for the prevention of postpartum hemorrhage during home births in rural Lao PDR: establishing a pilot program for community distribution. AB - Purpose: The purpose of this study was to gather the necessary data to support the design and implementation of a pilot program for women who are unable to deliver in a healthcare facility in the Lao People's Democratic Republic (PDR), by using community distribution of misoprostol to prevent postpartum hemorrhage (PPH). The study builds on an earlier research that demonstrated both support and need for community-based distribution of misoprostol in Lao PDR. Methods: This qualitative study identified acceptability of misoprostol and healthcare system needs at varying levels to effectively distribute misoprostol to women with limited access to facility-based birthing. Interviews (n=25) were undertaken with stakeholders at the central, provincial, and district levels and with community members in five rural communities in Oudomxay, a province with high rates of maternal mortality. Focus group discussions (n=5) were undertaken in each community. Results: Respondents agreed that PPH was the major cause of preventable maternal mortality with community distribution of misoprostol an acceptable and feasible interim preventative solution. Strong leadership, training, and community mobilization were identified as critical success factors. While several participants preferred midwives to distribute misoprostol, given the limited availability of midwives, there was a general agreement that village health workers or other lower level workers could safely administer misoprostol. Many key stakeholders, including women themselves, considered that these community-level staff may be able to provide misoprostol to women for self administration, as long as appropriate education on its use was included. The collected data also helped identify appropriate educational messages and key indicators for monitoring and evaluation for a pilot program. Conclusion: The findings strengthen the case for a pilot program of community distribution of misoprostol to prevent PPH in remote communities where women have limited access to a health facility and highlight the key areas of consideration in developing such a program. PMID- 29785141 TI - Validity of a method for the self-screening of cardiovascular risk. AB - Background: The validity of a cardiovascular risk self-screening method was assessed. The results obtained for self-measurement of blood pressure, a point-of care system's assessment of lipid profile and glycated hemoglobin, and a self administered questionnaire (sex, age, diabetes, tobacco consumption) were compared with the standard screening (gold standard) conducted by a health professional. Methods: Crossover clinical trial on a population-based sample from Girona (north-eastern Spain), aged 35-74, with no cardiovascular disease at recruitment. Participants were randomized to one of the two risk assessment sequences (standard screening followed by self-screening or vice versa). Cardiovascular risk was estimated with the Framingham-REGICOR function. Concordance between methods was estimated with the intraclass correlation coefficient (ICC). Sensitivity, specificity, and positive and negative predictive values were estimated, considering 5% cardiovascular risk as the cutoff point. ClinicalTrials.gov Registration #NCT02373319. Clinical Research Ethic Committee of the Parc de Salut Mar Registration #2014/5815/I. Results: The median cardiovascular risk in men was 2.56 (interquartile range: 1.42-4.35) estimated by standard methods and 2.25 (1.28-4.07) by self-screening with ICC=0.92 (95% CI: 0.90-0.93). In women, the cardiovascular risk was 1.14 (0.61-2.10) by standard methods and 1.10 (0.56-2.00) by self-screening, with ICC=0.89 (0.87-0.90). The sensitivity, specificity, and positive and negative predictive values for the self-screening method were 0.74 (0.63-0.82), 0.97 (0.95-0.99), 0.86 (0.77-0.93), and 0.94 (0.91-0.96), respectively, in men. In women, these values were 0.50 (0.30-0.70), 0.99 (0.98-1), 0.81 (0.54-0.96), and 0.97 (0.95-0.99), respectively. Conclusion: The self-screening method for assessing cardiovascular risk provided similar results to the standard method. Self-screening had high clinical performance to rule out intermediate or high cardiovascular risk. PMID- 29785143 TI - Pilot study of the antifibrotic effects of the multikinase inhibitor pacritinib in a mouse model of liver fibrosis. AB - Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients. In two Phase III clinical trials, pacritinib, however, demonstrated improvements in platelet counts and hemoglobin and reductions in transfusion burden in some patients with baseline cytopenias, suggesting it may improve bone-marrow function. Unlike ruxolitinib, pacritinib suppresses signaling through IRAK1, a key control point for inflammatory and fibrotic signaling. Purpose: To investigate potential antifibrotic effects of pacritinib in an animal model of liver fibrosis relevant to the observed course of human disease. Methods: Pacritinib, negative control (vehicle), and positive control (the angiotensin 2-receptor antagonist and PPARgamma partial agonist telmisartan) were assessed in the murine Stelic animal model, which mimics the clinically observed progression from hepatic steatosis to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Histopathological analysis used hematoxylin and eosin staining. Body and liver weight changes, nonalcoholic fatty liver disease activity scores, and plasma cytokeratin 18 fragment levels (a biomarker of hepatic necrosis) were measured. Results: Pacritinib-treated mice had significantly (P<0.01) reduced fibrotic areas in liver compared to vehicle control and significantly (P<0.05) lower levels of CK18. The antifibrotic effect of pacritinib was comparable to that of telmisartan, but without significant effects on fat accumulation. Conclusion: These results, the first to demonstrate hepatic antifibrotic effects for pacritinib in an animal model of liver disease, provide preliminary support for potential clinical applications of pacritinib in fibrotic diseases other than myelofibrosis. PMID- 29785145 TI - Linking product design to consumer behavior: the moderating role of consumption experience. AB - Background: Previous investigations of product design broadly link aesthetic, functional, and symbolic designs to sales growth, high turnover, and market share. However, the effect of product design dimensions on consumer willingness to-buy (WTB) and word-of-mouth (WOM) is virtually ignored by consumer researchers. Similarly, whether the consumption experience can differentiate the effect of the three product design dimensions on WTB and WOM is completely unknown. Using categorization theory as a lens, our study aims to explore the effect of product design dimensions on consumer WTB and WOM directly and indirectly through the moderation of the consumption experience. Methods: A convenience sample of (n=357) Chinese and (n=277) Korean shoppers was utilized to test the hypotheses in the fashion apparel industry. Results: Our results showed that the aesthetic design was more prominent in capturing consumer WTB for both Chinese and Koreans. Similarly, the aesthetic design was more salient in enhancing WOM for Chinese, whereas the symbolic design was more promising in terms of improving WOM for Koreans. Further, our moderation results demonstrated that the consumption experience could differentiate the effects of the three product design dimensions on consumer WTB and WOM for Chinese. By contrast, the consumption experience could only interact with the aesthetic design to improve WOM for South Koreans. Conclusion: To the best of authors' knowledge, the present study is one of the initial attempts to link three product design dimensions with consumer WTB and WOM in the fashion apparel context and explored whether consumption experience competes or complement with three product design dimensions to shape consumer WTB and WOM for Chinese and Koreans. PMID- 29785144 TI - The neuropsychology of emerging psychosis and the role of working memory in episodic memory encoding. AB - Background: Episodic memory encoding and working memory (WM) deficits are among the first cognitive signs and symptoms in the course of schizophrenia spectrum disorders. However, it is not clear whether the deficit pattern is generalized or specific in nature. We hypothesized that encoding deficits at an early stage of the disease might be due to the more fundamental WM deficits. Methods: We examined episodic memory encoding and WM by administering the California Verbal Learning Test, a 2-back task, and the Wisconsin Card Sorting Test in 90 first episode psychosis (FE) patients and 116 individuals with an at-risk mental state for psychosis (ARMS) compared to 57 healthy subjects. Results: Learning progress, but not span of apprehension, was diminished to a similar extent in both the ARMS and the FE. We showed that this was due to WM impairment by applying a structural equation approach. Conclusion: Thus, we conclude that verbal memory encoding deficits are secondary to primary WM impairment in emerging psychosis. PMID- 29785146 TI - Provider use of a participatory decision-making style with youth and caregivers and satisfaction with pediatric asthma visits. AB - Background: We conducted a randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to engage the youth during clinic visits. We examined whether the intervention was associated with 1) providers including youth and caregiver inputs more into asthma treatment regimens, 2) youth and caregivers rating providers as using more of a participatory decision-making style, and 3) youth and caregivers being more satisfied with visits. Methods: English- or Spanish-speaking youth aged 11-17 years with persistent asthma and their caregivers were recruited from four pediatric clinics and randomized to the intervention or usual care groups. The youth in the intervention group watched the video with their caregivers on an iPad and completed a one-page asthma question prompt list before their clinic visits. All visits were audiotaped. Generalized estimating equations were used to analyze the data. Results: Forty providers and their patients (n=359) participated in this study. Providers included youth input into the asthma management treatment regimens during 2.5% of visits and caregiver input during 3.3% of visits. The youth in the intervention group were significantly more likely to rate their providers as using more of a participatory decision-making style (odds ratio=1.7, 95% confidence interval=1.1, 2.5). White caregivers were significantly more likely to rate the providers as more participatory (odds ratio=2.3, 95% confidence interval=1.2, 4.4). Youth (beta=4.9, 95% confidence interval=3.3, 6.5) and caregivers (beta=7.5, 95% confidence interval=3.1, 12.0) who rated their providers as being more participatory were significantly more satisfied with their visits. Youth (beta=-1.9, 95% confidence interval=-3.4, 0.4) and caregivers (beta=-8.8, 95% confidence interval=-16.2, -1.3) who spoke Spanish at home were less satisfied with visits. Conclusion: The intervention did not increase the inclusion of youth and caregiver inputs into asthma treatment regimens. However, it did increase the youth's perception of participatory decision-making style of the providers, and this in turn was associated with greater satisfaction. PMID- 29785147 TI - Selection as a learning experience: an exploratory study. AB - Introduction: Research on selection for medical school does not explore selection as a learning experience, despite growing attention for the learning effects of assessment in general. Insight in the learning effects allows us to take advantage of selection as an inclusive part of medical students' learning process to become competent professionals. The aims of this study at Radboud University Medical Center, the Netherlands, were 1) to determine whether students have learning experiences in the selection process, and, if so, what experiences; and 2) to understand what students need in order to utilize the learning effects of the selection process at the start of the formal curriculum. Materials and methods: We used focus groups to interview 30 students admitted in 2016 about their learning experiences in the selection process. Thematic analysis was used to explore the outcomes of the interviews and to define relevant themes. Results: In the selection process, students learned about the curriculum, themselves, their relation to others, and the profession they had been selected to enter, although this was not explicitly perceived as learning. Students needed a connection between selection and the curriculum as well as feedback to be able to really use their learning experiences for their further development. Discussion: Medical school selection qualifies as a learning experience, and students as well as medical schools can take advantage of this. We recommend a careful design of the selection procedure, integrating relevant selection learning experiences into the formal curriculum, providing feedback and explicitly approaching the selection and the formal curriculum as interconnected contributors to students' development. PMID- 29785148 TI - The use of augmented reality glasses in central line simulation: "see one, simulate many, do one competently, and teach everyone". AB - Objective: The aim of this study was to investigate the feasibility of using augmented reality (AR) glasses in central line simulation by novice operators and compare its efficacy to standard central line simulation/teaching. Design: This was a prospective randomized controlled study enrolling 32 novice operators. Subjects were randomized on a 1:1 basis to either simulation using the augmented virtual reality glasses or simulation using conventional instruction. Setting: The study was conducted in tertiary-care urban teaching hospital. Subjects: A total of 32 adult novice central line operators with no visual or auditory impairments were enrolled. Medical doctors, respiratory therapists, and sleep technicians were recruited from the medical field. Measurements and main results: The mean time for AR placement in the AR group was 71+/-43 s, and the time to internal jugular (IJ) cannulation was 316+/-112 s. There was no significant difference in median (minimum, maximum) time (seconds) to IJ cannulation for those who were in the AR group and those who were not (339 [130, 550] vs 287 [35, 475], p=0.09), respectively. There was also no significant difference between the two groups in median total procedure time (524 [329, 792] vs 469 [198, 781], p=0.29), respectively. There was a significant difference in the adherence level between the two groups favoring the AR group (p=0.003). Conclusion: AR simulation of central venous catheters in manikins is feasible and efficacious in novice operators as an educational tool. Future studies are recommended in this area as it is a promising area of medical education. PMID- 29785149 TI - The pregnant female surgical resident. AB - Background: Surgery continues to be an intense, time-consuming residency. Many medical students decide against surgery as a profession due to the long work hours and family strain. The pregnant female surgical resident has an added stress factor compared to her male counterpart. Methods: We distributed an electronic, online 26-question survey to 32 general surgery programs in the southwestern region of the United States. Each program distributed our survey to the female surgical residents who had been pregnant during residency in the last 5 years. Each program was re-contacted 6 weeks after the initial contact. Most questions were in a 5-point Likert scale format. The responses were collected and analyzed using the Survey Monkey website. Results: An unvalidated survey was sent to 32 general surgery programs and 26 programs responded (81%). Each program was asked for the total number of possible responses from female residents that met our criteria (60 female residents). Seven of the programs (27%) stated that they have had zero residents pregnant. We had 22 residents respond (37%). Over half of the residents (55%) were pregnant during their 2nd or 3rd year of residency, with only 18% pregnant during a research year. Thirty-one percent had a lower American Board of Surgery In-Training Exam (ABSITE) score. Ninety percent of the residents were able to take 4 weeks or more for maternity leave. Most of the residents (95%) stated that they would do this again during residency given the opportunity, but many of the residents felt that returning back to work with a child at home was the most difficult part. Conclusion: Our preliminary study shows that the programs surveyed were accommodating to the female surgical resident. Nevertheless, despite adequate support from their program and an overall positive experience, many residents indicated that they had a decline in their education and performance. PMID- 29785150 TI - "Flipped classroom" for academic and career advising: an innovative technique for medical student advising. AB - Introduction: Career advising for medical students can be challenging for both the student and the adviser. Our objective was to design, implement, and evaluate a "flipped classroom" style advising session. Methods: We performed a single center cross-sectional study at an academic medical center, where a novel flipped classroom style student advising model was implemented and evaluated. In this model, students were provided a document to review and fill out prior to their one-on-one advising session. Results: Ninety-four percent (95% CI, 88%-100%) of the medical students surveyed felt that the advising session was more effective as a result of the outline provided and completed before the session and that the pre-advising document helped them gain a better understanding of the content to be discussed at the session. Conclusion: Utilization of the flipped classroom style advising document was an engaging advising technique that was well received by students at our institution. PMID- 29785151 TI - Non-alcoholic fatty liver disease: an update on diagnosis. AB - Background and aim: The non-alcoholic fatty liver disease (NAFLD) and its sub entity, the non-alcoholic steatohepatitis (NASH) represent a field of a tremendous progress in recent years. Clinicians need to remain updated with new data on pathogenesis and therapy. The present mini review aims to present some new scientific reports on the diagnosis of NAFLD and NASH for clinical practitioners. Methods: A systematic literature search of the main international databases was performed. We looked for seminal and innovative papers published in main international languages. A narrative review of the topic was consequently written. Results: This review describes new data on the diagnosis of NAFLD including NASH. Liver punction biopsy remains the gold standard. However many patients and clinicians prefer to use noninvasive methods. We present the serological tests and the imaging methods used to diagnose inflammation and fibrosis occurring in NAFLD and NASH. Conclusions: NAFLD-NASH are multifaceted entities that have to be diagnosed and treated by skilled and informed practitioners. PMID- 29785152 TI - Association of midline discrepancy with tempromandibular joint disorder. A systematic review. AB - Aim: The aim is to evaluate the association between midline discrepancies and tempromandibular disorders (TMDs). Methods: Literature search was performed by using various search engines to include human studies in English. TMDs include a wide variety of signs and symptoms such as pain in and around TMJ, jaw muscles, clicking and locking of jaws, pain during mandibular movement and restricted mandibular movements. The etiology is multifactorial, including one or several of the following factors like severe malocclusions (increased overjet, retroclination of incisors, cross bite, CR CO discrepancies etc), stress and psychological factors, structural abnormalities as possible etiology. There are controversies concerning the association between different traits of malocclusion and TMDs. The aim of the present study was to find out any association between signs and symptoms of TMDs with midline discrepancies, which represent an important trait of malocclusion. Result: Of the seven studies evaluated in this systematic review for investigating the association between midline discrepancy and TMD, six had moderate grade (B) of evidence. Four studies of moderate grade evidence (B) showed a significant association between the presence of midline shift and TMDs, and the remaining studies (two) had non-significant association. Only one study had a strong grade of evidence (A) and interestingly it denies the presence of midline shift to be a causative factor for TMDs. So, it can be concluded that the results are inconclusive regarding the association of midline discrepancies with TMDs. Nonetheless, this requires concrete evidence which necessitates further long term research into this aspect. PMID- 29785153 TI - Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population. AB - Aim: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance. Methods: Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Results: 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases. Conclusion: Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive. PMID- 29785154 TI - Detection of coronary artery disease by reduced features and extreme learning machine. AB - Objective: Cardiovascular diseases generate the highest mortality in the globe population, mainly due to coronary artery disease (CAD) like arrhythmia, myocardial infarction and heart failure. Therefore, an early identification of CAD and diagnosis is essential. For this, we have proposed a new approach to detect the CAD patients using heart rate variability (HRV) signals. This approach is based on subspaces decomposition of HRV signals using multiscale wavelet packet (MSWP) transform and entropy features extracted from decomposed HRV signals. The detection performance was analyzed using Fisher ranking method, generalized discriminant analysis (GDA) and binary classifier as extreme learning machine (ELM). The ranking strategies designate rank to the available features extracted by entropy methods from decomposed heart rate variability (HRV) signals and organize them according to their clinical importance. The GDA diminishes the dimension of ranked features. In addition, it can enhance the classification accuracy by picking the best discerning of ranked features. The main advantage of ELM is that the hidden layer does not require tuning and it also has a fast rate of detection. Methodology: For the detection of CAD patients, the HRV data of healthy normal sinus rhythm (NSR) and CAD patients were obtained from a standard database. Self recorded data as normal sinus rhythm (Self_NSR) of healthy subjects were also used in this work. Initially, the HRV time-series was decomposed to 4 levels using MSWP transform. Sixty two features were extracted from decomposed HRV signals by non-linear methods for HRV analysis, fuzzy entropy (FZE) and Kraskov nearest neighbour entropy (K-NNE). Out of sixty-two features, 31 entropy features were extracted by FZE and 31 entropy features were extracted by K-NNE method. These features were selected since every feature has a different physical premise and in this manner concentrates and uses HRV signals information in an assorted technique. Out of 62 features, top ten features were selected, ranked by a ranking method called as Fisher score. The top ten features were applied to the proposed model, GDA with Gaussian or RBF kernal + ELM having hidden node as sigmoid or multiquadric. The GDA method transforms top ten features to only one feature and ELM has been used for classification. Results: Numerical experimentations were performed on the combination of datasets as NSR CAD and Self_NSR- CAD subjects. The proposed approach has shown better performance using top ten ranked entropy features. The GDA with RBF kernel + ELM having hidden node as multiquadric method and GDA with Gaussian kernel + ELM having hidden node as sigmoid or multiquadric method achieved an approximate detection accuracy of 100% compared to ELM and linear discriminant analysis (LDA)+ELM for both datasets. The subspaces level-4 and level-3 decomposition of HRV signals by MSWP transform can be used for detection and analysis of CAD patients. PMID- 29785155 TI - The volume of the cerebellum in the second semester of gestation. AB - Background and aims: The cerebellum ("little brain"), the largest part of hind brain, lies in the posterior cranial fossa, beneath the occipital lobe and dorsal to the brainstem. It develops over a long period: it is one of the first structures in the brain to begin to differentiate, but one of the last to mature. The use of ultrasonography has significantly improved the evaluation of fetal growth and development and has permitted prenatal diagnosis of a variety of congenital malformations.The aim of our study was to evaluate the cerebellar growth and development using 2 different measuring techniques: microMRI and ultrasound technique. The cerebellum measurements were related to gestational age. Methods: We used 14 human fetuses corresponding to 15-28 gestational weeks, immersed in a 9% formalin solution. Magnetic Resonance Imaging (MRI) was performed by employing a Bruker BioSpec 70/16USR scanner (Bruker BioSpin MRI GmbH, Ettlingen, Germany), operated at 7.04 Tesla for cerebellar volume measurement. Ultrasonographic measurements of the cerebellum diameter were performed on 14 pregnant women, 15 - 28 gestational weeks. Ultrasound scan used 5 10 MHZ for transvaginal approach. Taking into consideration the values of the cerebellum dimensions and considering the general shape of the cerebellum as a transverse ellipsoid, the volume of the cerebellum was calculated by a mathematical formula for ellipsoid volume. Results: The study correlates the measurements from the microMRI study with the ultrasounds data and the results are superposable. Both established the exponential volume growth after the 22-23 GW. We used the ellipsoid volume formula for the cerebellar volume using the half of the three diameters of the cerebellum determined by ultrasound measurements:Cerebellar Volume = Ellipsoid volume = 3/4 pi r1 r2 r3. Conclusion: There is a linear correlation between the microMRI measurements and ultrasound determinations. Based on all collected data we could apply an easy formula to calculate the volume of cerebellum, a useful criterion in the evaluation of the cerebellar development and the appreciation of the gestational age. PMID- 29785156 TI - Correlations of aldehyde dehydrogenase-1 (ALDH1) expression with traditional prognostic parameters and different molecular subtypes of breast carcinoma. AB - Background and aim: Breast cancer, a heterogeneous disease, is the most common cause of cancer-related death in women worldwide. Despite considerable developments in treatment modalities, a subset of patients with advanced-stage breast carcinoma display poor prognosis. Breast cancer heterogeneity and risk of recurrence could be explained with the help of cancer stem cell hypothesis. Stem cells have the capacity to self-renew and differentiate into multiple cell types. Aldehyde dehydrogenase-1 (ALDH1), an enzyme responsible for the oxidation of intracellular aldehydes, contributes to normal and tumor stem cell differentiation. Invasion and metastasis in breast cancer are found to be mediated by a subpopulation of tumor cells which exhibit stem cell-like features and express ALDH1.The aim was to document ALDH1 expression in breast carcinoma and find its association with other clinico-pathologic prognostic parameters. Study design: This was a cross-sectional observational study. Methods: A total of 62 patients with breast carcinoma undergoing mastectomy were included in this study. The tumors were classified into molecular subtypes by assessing immunohistochemical (IHC) expression of ER, PgR, HER2 and Ki-67 according to St. Gallen Consensus Conference 2013. ALDH1 expression was studied by IHC and correlated with clinicoathological parameters. Statistical analysis: Statistical analysis was done using Graph Pad software (Prism 5 version) for Windows 7. A p value <0.05 was considered statistically significant. Results and analysis: Out of 62 tumors, 35 tumors (56.4%) showed ALDH1 positivity. ALDH1 expression was significantly associated with larger size, lymph node involvement, higher grade, higher stage and HER2+ or triple negative tumors. Conclusion: This study suggests that ALDH1 expression is associated with poor prognostic parameters and aggressive tumor behavior. Larger population-based prospective trials on Indian patients are required to validate these results. PMID- 29785157 TI - Cancer risk associated with living at high altitude in Ecuadorian population from 2005 to 2014. AB - Background and aims: Cancer is a leading cause of death in Ecuador with high social and economic impact. This study aims to determinate the influence of living at a high altitude on the risk of developing or dying from cancer among the Ecuadorian population. Methods: This is an ecological and epidemiological analysis of cancer mortality and prevalence rates, based on national data from the Ecuadorian National Statistics and Census Institute, corresponding to the period between 2005 and 2014. This study includes the analysis of various types of cancer: gastric, colorectal, hepatic/bile duct, breast, uterine/cervix, and lymphatic/hematopoietic, using rates of mortality and prevalence. Additionally, the association between the risk of getting or dying from cancer and living at high altitude was investigated. This comparison was made between the population living in Highlands, over 2000 meters above sea level, and low-lying regions. Results: Living at high altitude was associated with a higher prevalence of cancer and also with a high mortality rate due to cancer. Risk of getting cancer was related to living at a higher altitude, as well as an increased risk of death by cancer: gastric (OR:1.204; p<0.001), colorectal (OR:1.421; p<0.001), hepatic/bile duct (OR:1.184; p<0.001), breast (OR:1.067; p=0.030), or lymphatic/hematopoietic neoplasms (OR:1.135; p<0.001). Conclusions: Through an epidemiologic analysis, the association between developing or dying from cancer and living at high altitude was obtained. However, further researche is needed to clarify these findings, something that could have a substantial impact on cancer prevention. PMID- 29785158 TI - Obtaining adequate surgical margin status in breast-conservation therapy: intraoperative ultrasound-guided resection versus specimen mammography. AB - Background and aim: The purpose of breast-conserving surgery (BCS) for women with cancer is to perform an oncological radical procedure with disease-free margins at the final histological assessment and with the best aesthetic result possible. Intraoperative resected specimen ultrasound and intraoperative resected specimen mammography may reduce the rates of positive margins and reexcision among patients undergoing conserving therapy. Our objective is to compare the two methods with the histopathological results for a preset cut off and asses which parameters can influence the positive margin status. Method: A prospective study was performed on 83 patients who underwent breast conservation surgery for early breast cancer (pT1-3a pN0-1 M0) between 2014 and 2016. After excision the specimen was oriented in the operating room by the surgeon. Metallic clips and threads were placed on margins: one clip and the long thread at 12 o'clock, two clips and the short threads at 9 o'clock. The next step was intraoperative ultrasound assessment of the specimen. For the margins under 2 mm we performed selective margin shaving, followed by mammography to identify and document the lesion and finally histopathological examination of the specimen with reporting the gross and microscopic margins. The positive margins required re-excision or boost of radiation at the posterior or anterior margins, depending on the case. Results: We set a cut-off at 2 mm. The sensitivity and specificity of the intraoperative margin assessment via the ultrasound method were 90.91% (95% CI 70.84-98.88%) and 67.21% (95% CI 54-78.69%) respectively. The sensitivity and specificity of the intraoperative margin assessment via the mammographic procedure were 45.45% (95% CI 24.39-67.79%) and 85.25% (95% CI 73.83-93.02%) respectively. There was positive correlation between the histopathological and intraoperative ultrasound exam (p=0.018) and negative correlation between the histopathological exam and the post-operative mammographic exam (p=0.68). We found a positive correlation between the positive margin status and age (<40), preoperative chemotherapy, intraductal carcinoma, inflammatory process around the tumor, and the immunohistochemical triple negative profile. Conclusions: According to our results, the intraoperative ultrasound of the breast specimen for a cutt-off at 2 mm can decrease the rates of margin positivity compared to the mammographic procedure and has the potential to diminish the number of subsequent undesired re-excisions. PMID- 29785159 TI - Assessment of the quality of life and performance status in patients with oral submucous fibrosis in central India. AB - Background and aims: Measuring quality of life in patients with oral submucous fibrosis is of utmost importance in assessing treatment outcomes. This study examined the impact of oral submucous fibrosis and its treatment on the quality of life and performance status of persons with oral submucous fibrosis. Methods: Quality of life was measured in patients with oral submucous fibrosis using the European Organization for Research and Treatment of Cancer Quality of Life head and neck 35 Questionnaire (EORTC QLQ-C35); performance status was measured by Performance Status Scale for Head and Neck Cancer Patients (PSS-HN), at four points in time: baseline, one month, two months and three months after start of treatment. Results: At the end of third month Group A and Group B showed 78% and 85% increase in mouth opening respectively. While the burning sensation of oral mucosa was decreased by 72% and 88% in group A and group B respectively (Z>1.96, P<0.05), there were significant differences in patients' quality of life and functioning at three points in time (P < 0.05). Conclusion: The European Organization for Research and Treatment of Cancer Quality of Life head and neck 35 Questionnaire and Performance Status Scale for Head and Neck Cancer Patients can be used successfully in potentially malignant disorders like oral submucous fibrosis. The results in this study will surely be a good guide forother studies on oral submucous fibrosis. PMID- 29785161 TI - Prevalence and psychological stress in recurrent aphthous stomatitis among female dental students in Saudi Arabia. AB - Introduction: Recurrent Aphthous Stomatitis (RAS) is a common oral mucosal disorder which is characterized by recurrent ulcerations mainly confined to non keratinized oral mucosa. Though the exact etiology is imprecise, stress and anxiety were found to be linked with the onset of RAS. The present study was directed to know the prevalence of RAS among female dental students in King Khalid University, to find out the association between RAS and psychological stress and the effectiveness of Hospital Anxiety and Depression scale (HADS) in finding out the psychological profile of RAS patients. Method: 122 female dental students of age group 17 to 25 years were selected for the study. Subjects with relevant medical problems and deleterious habits were excluded. A questionnaire comprising general stress related questions and HAD scale were used to assess stress. Those who were giving history of ulcer were diagnosed as RAS based on the clinical features. The questionnaire results were used for statistical analysis and processed. Result: 14% of the total students were having RAS. 70% could correlate the onset of ulcer with certain specific factors; stress being the major causative agent (91%). In HAD scale, 88% of students were having anxiety and 65% had depression; all patients with depression had anxiety. Conclusion: The prevalence of RAS in female dental students in KKU was around 14%. There is a strong relationship between psychological stress and RAS, as in most of the other studies. HAD scale alone can be used for detecting the psychological factor in RAS. PMID- 29785160 TI - Observational study of the bisphosphonate-related osteonecrosis of jaws. AB - Introduction: The bisphosphonate-related osteonecrosis of the jaw was first referred to in 2003. Bisphosphonates action is focused on the osteoclasts. The drastic inhibition of the osteoclastic function is harmful for the jaws which are the only bones of the human skeleton in relative contact with the external environment. The adverse effects of the bisphosphonate-related therapy include the pathology for which they are prescribed, the atypical fractures in pathological bone. Method: The aim of this research was to analyze the risk factors and the treatment methods in case of osteonecrosis of the jaws. To achieve these goals, the author analyzed the observation sheets of the patients admitted to the Oral and Maxillofacial Surgery Clinic during the period 2010 2015. The inclusion criteria were as follows: treatment with bisphosphonates, current or previous; the lesions of the mucous gingiva of the maxillaries followed by exposed necrotic bone, older than 8 weeks, with no tendency of healing; specific radiological image showing extended osteolysis with diffuse outline or radiopacity surrounded by radio-transparence, representing the necrotic bone sequestered; no metastasis in the necrotic maxillary bone; patient with no medical background of cervical-facial radiations. The patients who met these criteria were admitted in the study after signing the informed consent. Afterwards, the information found in the notes of the observational sheet (anamnesis, general examination and the imagistic investigation, treatment, postoperative recovery, prescription, postoperative recommendations) were gathered and submitted for statistic analysis. Results: Of the 20 patients in total, 13 were women and 7 men, of ages ranging from 43 to 83. The most numerous cases were registered in the seventh age decade. All patients included in the study had lesions of the gingival maxillary mucosal areas with exposure of the subjacent necrotic bone. 60% of them were under intravenous treatment with zoledronic acid (Zometa(r)). A single patient was under oral treatment with bisphosphonates. 19 of these 20 patients developed osteonecrosis following a dental extraction while one case was due to the instability of the mandibular mobile prosthesis. 61% of the patients included in the study developed a necrotic process in the mandibular bone, 80% of the localizations were in the posterior area. As first intention, the choice of treatment was represented by local lavages with antiseptic solutions, general antibiotics and sequestrectomy. Of these patients, a third had relapsed and needed radical surgery treatment. Conclusions: Prevention of the bisphosphonate-related osteonecrosis of the jaw represents the best method of treatment. The development of bone sequesters damages the volume of the maxillary bone as such, reducing the chances for prosthetic functional rehabilitation of the dento-maxillary system. An increase in the quality of life by oral restoration of these patients may represent a challenge. PMID- 29785162 TI - Evaluation of chromatic changes of a nanocomposite resin using the new whitness index. AB - Background and aims: To evaluate the staining effects of two brands of coffee and the bleaching efficiency of two in-office bleaching methods, upon different opacities of a commercial nanocomposite. Methods: Twenty four specimens of each opacity, A3 Dentin, A3 Body and A3 Enamel, were fabricated from Filtek Supreme (3MEspe). The specimens were further divided into two groups (n=12) and were immersed in two coffee solutions (Bio Organic Coffee Bellarom, 100% Arabica, and Iulius Meinl Coffee), for 24 hours. Between the staining sessions, the specimens were stored in sterile water, at 37 degrees C. Each group was further divided into three (n=4), in order to be bleached, as follows: Group 1 - Beyond 35% in office, for 4 applications of 15 minutes each, Group 2 - Zoom Day White 6% in office, for 4 applications of 15 minutes each, Group 3 - Control Group, stored in sterile water. Color values were measured with a dental spectrophotometer Vita EasyShade 4.0 and five measurements were recorded for each sample at a time. Lightness L*, color coordinates a* and b* were recorded, at baseline, after staining in coffee and after bleaching. Whiteness index (WID) of the three composite resins (A3D, A3B, A3E) in the three moments were calculated, as well as the color difference Delta E* correspondent to the staining and bleaching process. Data were analyzed using one-way repeated measures ANOVA and the WID index was calculated WID (p<0.05). Univariate analysis of variance was performed for assessing the influence of staining solution upon composite resins, as well as for testing the effect of bleaching agents. The significance level was set at alpha=0.05 and pairwise comparisons were adjusted by the Least Significant Difference method. Results: The pairwise comparisons showed no significant difference between the effects of the two bleaching agents upon the WID, meaning that they induce almost similar color changes. The results of the univariate ANOVA test indicated a significant effect of the composite resin and the staining solution upon the WID (p<0.05). However, no significant interaction effect was found between the composite resin and the staining solution (p=0.095). There was a significant difference in the staining effect of the two coffee solutions only for A3B and A3E composite resins (p<0.05). Conclusions: The chromatic changes of the nanocomposite resin could be evaluated by the variation of the whiteness index. The staining effect induced by the two types of coffee was similar. The most effective protocol was the in-office bleaching method based on Beyond 35%. PMID- 29785163 TI - Management of intrinsic discoloration using walking bleach technique in maxillary central incisors. AB - Introduction: Non-vital bleaching is a non-invasive technique to treat the intrinsic discoloration of teeth of several etiologies. Hydrogen peroxide and sodium perborate are commonly used bleaching agents. Aim: The aim of this case report is to demonstrate the non-vital bleaching technique in maxillary anterior teeth. Method: Maxillary central incisors were isolated with rubber dam and root canal treatment was performed. Barrier space preparation was done using a heated instrument. Glass ionomer cement was used a barrier material. Mixture of hydrogen peroxide and sodium perborate was placed in the canal and sealed with intermediate restorative material. After 1 week, the procedure was repeated to achieve the desired results. Conclusion: Non-vital bleaching is a minimally invasive procedure to restore the esthetics of a discolored non-vital tooth. However, care should be taken to prevent any post-operative complications. PMID- 29785164 TI - Endodontic management of mandibular second premolar with three canals. AB - Mandibular premolar can present a complex pulp anatomy. Apart from the usual single root and single canal a many other variations may be seen. Hence not only a thorough knowledge of the root canal anatomy but also it's variations are indispensable pre requisites for the success of any endodontic treatment. Good magnification and CBCT scans will definitely be beneficial for successful endodontic treatment. The present case provides evidence that mandibular premolars may have more than one canal. PMID- 29785165 TI - Thymic carcinoma - a rare case report. AB - Introduction: Thymic carcinoma is a rare, invasive mediastinal neoplasm with a tendency to metastasize. They constitute a heterogeneous group of tumors that present differently in terms of both behavior and prognosis. Case report: We present a case of thymic carcinoma in a 55-year-old male patient known to suffer from Myasthenia gravis, whose chief complaints were fatigability, ptosis and coughing. All electromyography studies were done along with excision biopsy to reach the definitive diagnosis. Results and conclusion: The histopathological diagnosis of Thymic carcinoma-Lymphoepithelial variant was established. Though no definite staging system exists for the thymic carcinoma, prognosis of the patient was ascertained by using Weissferdt-Moran system, Masaoka and Tsuchiya TNM staging systems. Involvement of the pleural and the pericardial structures leads to poor prognosis, though no distant metastases or lymph nodal metastasis were evident. PMID- 29785166 TI - Takotsubo syndrome induced by malignant pheochromocytoma in a patient with type 2 papillary renal cell carcinoma - a case report. AB - The clinical presentation of the Takotsubo syndrome mimics an acute coronary syndrome with chest pain, ischemia-like ECG changes, mild to moderate myocardial enzyme elevation, and apical ballooning on echocardiography and ventriculography. On coronary angiography, epicardial coronary arteries are either normal or exhibit minimal atherosclerotic changes. Primary Takotsubo syndrome usually occurs in postmenopausal women in whom symptoms are triggered by emotional or physical stress, associated with catecholamine surges. Secondary Takotsubo syndrome may have multiple causes, including an increased catecholamine release due to pheochromocytoma. We present the case of a 56-years-old woman with confirmed Takotsubo syndrome who was later diagnosed with pheochromocytoma and type 2 papillary renal cell carcinoma. PMID- 29785168 TI - Elimination of lymphatic filariasis as a public health problem from the Cook Islands. AB - Background: The Cook Islands has a long history of high-endemicity lymphatic filariasis (LF) transmitted by Aedes vector mosquitoes. Though the infection prevalence had declined between 1975 and 1999 following episodic treatment activities, still infection was widespread with pockets of persistent infection. Beginning in 1999, the Cook Islands embarked on a national program, in partnership with Pacific Programme to Eliminate LF (PacELF), to eliminate LF as a public health problem. Methods: All 12 inhabited islands were identified as endemic, and six rounds of mass drug administration (MDA) with once-yearly, single-dose albendazole plus diethylcarbamazine (DEC) were implemented during 2000-2006 to interrupt transmission of LF. Surveys carried out at the baseline, mid-term, stop-MDA, and post-MDA periods assessed LF antigen (Ag) prevalence in children and adults. Historical data, health workers' observations, and hospital records were used to assess the trend and burden of chronic disease. Results: The baseline Ag prevalence (1999) ranged from 2.0% in Manihiki to > 18.0% in Aitutaki, Mitiaro, and Pukapuka, and the national average Ag prevalence was 8.6%. MDA, carried out with a national treatment coverage over six annual rounds of MDA ranging from 63.5 to 96.7% in different years, was stopped in 2007. By then, the national Ag prevalence had declined to 0.27%. The post-MDA surveillance survey results (2013-2014) showed that Ag prevalence had fallen to 0% in 11/12 islands, and the national prevalence was only 0.03%. Chronic filarial disease had almost entirely disappeared. Conclusion: The Cook Islands met all the criteria required for the World Health Organization (WHO) to acknowledge elimination of LF as a public health problem, as it did officially in 2016. This success also confirms that LF, even when transmitted by Aedes mosquitoes that are recognized to be more efficient than other vector species, can be eliminated as a public health problem by six rounds of MDA. PMID- 29785167 TI - The 3D laparoscopic approach for radical prostatectomy overcomes the hurdles of metabolic syndrome. PMID- 29785170 TI - Cost-Effectiveness of Olaratumab in Combination with Doxorubicin for Patients with Soft Tissue Sarcoma in the United States. AB - Background: Standard first-line treatments for advanced soft tissue sarcoma (STS) have changed little for 40 years, and outcomes have been poor. Recently, the United States (US) Food and Drug Administration conditionally approved olaratumab in combination with doxorubicin (Olara + Dox) based on a randomized phase II trial that reported a significant 11.8-month improvement in median survival versus single-agent doxorubicin (Dox). The present study investigated the cost effectiveness of Olara + Dox compared with Dox and five other standard-of-care regimens from the US payer perspective. Methods: An economic model was constructed to estimate costs and outcomes over patients' lifetimes from start of therapy. Progression-free and overall survival were based on survival analysis of patient-level data and a meta-analysis. Adverse-event rates were based on trials. Costs were from published sources. Results: Olara + Dox resulted in an estimated additional 1.27 life-years (LYs) compared with Dox, with an increase in total expected lifetime costs of $133,653. The incremental cost-effectiveness ratio (ICER) was estimated at $105,408 per LY gained; in a fully incremental analysis, all other regimens were dominated (higher costs and lower LYs or a higher ICER). Conclusion: Olara + Dox is cost-effective for STS treatment compared with Dox and other standard-of-care regimens at willingness-to-pay thresholds of $150,000 per LY and above. PMID- 29785169 TI - Self-reported functional, communicative, and critical health literacy on foodborne diseases in Accra, Ghana. AB - Background: Although substantial progress has been made in reducing total mortality resulting from foodborne diseases, diarrheal illness are still the second most common illnesses among children. In Ghana, foodborne diseases have consistently been among the top 20 causes of outpatient illness over the last couple of decades. This study, therefore, examines health literacy on foodborne diseases and the relative effects of health literacy on self-rated health. Methods: Foodborne diseases are major causes of morbidity and mortality globally. A mixed-method approach was used for this study. A survey questionnaire and an in depth interview guideline were administered to samples of 401 and 30 individuals, respectively. We undertook reliability and validity analyses. ANOVA and chi square tests were undertaken to assess bivariate association between health literacy and demographic variables as well as health status. Ordinal logistic regression models were used to examine the relative effects of health literacy on self-rated health status controlling for individual characteristics. Results: The instrument was internally consistent (Cronbach alpha = 0.744) and valid. On health literacy, 40% of the respondents reported not to require help when they are given information on foodborne diseases to read by a doctor, nurse, or pharmacist. Approximately 60% of respondents need help with completing or filling out hospital documents. Educational level was found to be positively related to functional health literacy. Ordinal logit regression models showed that health literacy is a predictor of self-rated health after controlling for demographic variables. Conclusion: Functional literacy is relatively low in the community. There is a positive association between educational level and functional health literacy. The study has also demonstrated the direct positive relationship between health literacy and health status controlling for covariates. Subsequent studies will need to examine multiple level dimensions of health literacy with direct link between specific foodborne diseases and health literacy. PMID- 29785171 TI - Atherosclerosis and Autoimmunity. PMID- 29785172 TI - Graft versus Host Disease: From Basic Pathogenic Principles to DNA Damage Response and Cellular Senescence. AB - Graft versus host disease (GVHD), a severe immunogenic complication of allogeneic hematopoietic stem cell transplantation (HSCT), represents the most frequent cause of transplant-related mortality (TRM). Despite a huge progress in HSCT techniques and posttransplant care, GVHD remains a significant obstacle in successful HSCT outcome. This review presents a complex summary of GVHD pathogenesis with focus on references considering basic biological processes such as DNA damage response and cellular senescence. PMID- 29785174 TI - Communication in mental health nursing - Bachelor Students' appraisal of a blended learning training programme - an exploratory study. AB - Background: It is important that mental health nursing students at Bachelor level obtain effective communication skills. Many students dread the fact that in the mental health field they will encounter patients and relatives with various backgrounds and personalities. Large classes and limited teaching resources in nursing education are challenging. To prepare students for mental health nursing practice, a communication skills course based on the blended learning method was developed and carried out at two different campuses.The aim of the study is to explore Bachelor nursing students' appraisal of blended learning methods for enhancing communication skills in mental health nursing. Methods: This study employed an exploratory design. Teaching and information materials were available on the learning management system (LMS). Videotaped role play training was carried out in the Simulation Department. Data were collected after the course by means of a questionnaire with closed and open-ended questions. The response rate was 59.2%. Quantitative data were analysed using the Statistical package for the Social Sciences (SPSS) and the Kruskal Wallis test, while qualitative data were analysed by content analysis based on Graneheim and Lundman's approach. Results: No impact of background variables was observed. Students appreciated teachers' participation in role play and immediate feedback was considered especially important for learning outcomes. The students perceived that their communication skills and knowledge had improved after completing the blended learning programme. Conclusions: According to the nursing students, blended learning is an appropriate method for improving communication skills in preparation for mental health nursing. Blended learning makes it possible to build flexible courses with limited resources. PMID- 29785176 TI - Thrombin generation in low plasma volumes. AB - Accurate thrombin generation determination by calibrated automated thrombinography can be sustained when reducing the plasma and reagent volumes up to half, but not for higher reductions or plasma dilutions. PMID- 29785173 TI - Phytochemicals That Influence Gut Microbiota as Prophylactics and for the Treatment of Obesity and Inflammatory Diseases. AB - Gut microbiota (GM) plays several crucial roles in host physiology and influences several relevant functions. In more than one respect, it can be said that you "feed your microbiota and are fed by it." GM diversity is affected by diet and influences metabolic and immune functions of the host's physiology. Consequently, an imbalance of GM, or dysbiosis, may be the cause or at least may lead to the progression of various pathologies such as infectious diseases, gastrointestinal cancers, inflammatory bowel disease, and even obesity and diabetes. Therefore, GM is an appropriate target for nutritional interventions to improve health. For this reason, phytochemicals that can influence GM have recently been studied as adjuvants for the treatment of obesity and inflammatory diseases. Phytochemicals include prebiotics and probiotics, as well as several chemical compounds such as polyphenols and derivatives, carotenoids, and thiosulfates. The largest group of these comprises polyphenols, which can be subclassified into four main groups: flavonoids (including eight subgroups), phenolic acids (such as curcumin), stilbenoids (such as resveratrol), and lignans. Consequently, in this review, we will present, organize, and discuss the most recent evidence indicating a relationship between the effects of different phytochemicals on GM that affect obesity and/or inflammation, focusing on the effect of approximately 40 different phytochemical compounds that have been chemically identified and that constitute some natural reservoir, such as potential prophylactics, as candidates for the treatment of obesity and inflammatory diseases. PMID- 29785175 TI - How to fit allergen immunotherapy in the elderly. AB - Asthma, allergic rhinitis (AR) and atopic dermatitis are very common in young people, but in the latest decades it was increasingly recognized that also individuals of higher ages, including the population over 65 years, are concerned. Actually, it is now acknowledged the aging does not considerably alter the immune response to allergens. Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy, but elderly people are commonly excluded from AIT, except the cases of insect sting allergy. A number of recent studies showed that aged individuals also successfully respond to AIT for respiratory allergy. Therefore, there is no reason to exclude elder patients from AIT. Anyhow, clinical conditions that are considered absolute or relative contraindications are quite frequent in this aged population, thus the risk/benefit ratio must be carefully evaluated for each patient, taking into account that the more frequent occurrence of co-morbidities and the consequent need of daily-based multidrug regimen can favor adverse effects. An important issue concern the ability of AIT, and particularly of sublingual immunotherapy, to significantly improve the quality of life, that often is particularly impaired in the elderly, reducing symptoms and drugs consumption. PMID- 29785177 TI - Characterization of new microsatellite markers based on the transcriptome sequencing of Clematis finetiana. AB - Background: Clematis is the biggest genus in the family Ranunculaceae with about 300 species. Clematis is also a globally important commercial group of flowers, especially in the United States and European countries. Their petals with different colors and shapes make the genus the "Queen of the Vines". However, the genomic information and phylogeny of Clematis based on existing molecular studies are limited. In this paper, new microsatellites (SSR) markers were identified from the transcriptome data of C. finetiana obtained using the Illumina paired end sequencing technology. Results: Sequences on a total of 71,900 high-quality unigenes with the mean length of 865 bp were produced in this study. There were 6192unigenes annotated and classified into 49 functional sub-groups in three main ontology categories in GO (Gen Ontology) database,14,022 unigenes mapped to COGs (Clusters of Orthologous Groups) database and classified into 25 functional categories, and 21,494 unigenes obtained and divided into 128 pathways of KEGG (Kyoto Encyclopedia of Genes) Database. A total of 7532 SSRs were discovered from 6337 unigenes. We randomly tested 210 primer pairs, of which 52 primer pairs were able to generate specific products, and 19 possessed polymorphism in the 13 wild populations of six species from Clematis, which were used as a test material. Conclusions: The dataset of C. finetiana transcriptome and the identified new SSR markers will promote genetic research and breeding effort in Clematis. PMID- 29785179 TI - Nanoformulation of Brain-Derived Neurotrophic Factor with Target Receptor Triggered-Release in the Central Nervous System. AB - Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)-b-poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a core-shell structure. Molecular dynamics simulations suggest that binding between BDNF and PEG-PLE is mediated through electrostatic coupling as well as transient hydrogen bonding. The formation of Nano-BDNF complex stabilizes BDNF and protects it from nonspecific binding with common proteins in the body fluid, while allowing it to associate with its receptors. Following intranasal administration, the nanoformulation improves BDNF delivery throughout the brain and displays a more preferable regional distribution pattern than the native protein. Furthermore, intranasally delivered Nano-BDNF results in superior neuroprotective effects in the mouse brain with lipopolysaccharides-induced inflammation, indicating promise for further evaluation of this agent for the therapy of neurologic diseases. PMID- 29785178 TI - Functionally Graded, Bone- and Tendon-Like Polyurethane for Rotator Cuff Repair. AB - Critical considerations in engineering biomaterials for rotator cuff repair include bone-tendon-like mechanical properties to support physiological loading and biophysicochemical attributes that stabilize the repair site over the long term. In this study, UV-crosslinkable polyurethane based on quadrol (Q), hexamethylene diisocyante (H), and methacrylic anhydride (M; QHM polymers), which are free of solvent, catalyst, and photoinitiator, is developed. Mechanical characterization studies demonstrate that QHM polymers possesses phototunable bone- and tendon-like tensile and compressive properties (12-74 MPa tensile strength, 0.6-2.7 GPa tensile modulus, 58-121 MPa compressive strength, and 1.5 3.0 GPa compressive modulus), including the capability to withstand 10 000 cycles of physiological tensile loading and reduce stress concentrations via stiffness gradients. Biophysicochemical studies demonstrate that QHM polymers have clinically favorable attributes vital to rotator cuff repair stability, including slow degradation profiles (5-30% mass loss after 8 weeks) with little-to-no cytotoxicity in vitro, exceptional suture retention ex vivo (2.79-3.56-fold less suture migration relative to a clinically available graft), and competent tensile properties (similar ultimate load but higher normalized tensile stiffness relative to a clinically available graft) as well as good biocompatibility for augmenting rat supraspinatus tendon repair in vivo. This work demonstrates functionally graded, bone-tendon-like biomaterials for interfacial tissue engineering. PMID- 29785180 TI - Career Choices and Career Progression of Junior Doctors in Dermatology: Surveys of UK Medical Graduates. AB - Objective: To report UK-trained doctors' career choices for dermatology, career destinations, and factors influencing career pathways. Methods: Multicohort multipurpose longitudinal surveys of UK-trained doctors who graduated between 1974 and 2015. Results: In all, 40,412 doctors (58% of graduates) responded in year 1, 31,466 (64%) in year 3, and 24,970 (67%) in year 5. One year after graduation, 1.7% of women and 0.6% of men made dermatology their first choice but by five years after graduation the respective figures were 1.0% and 0.7%. Compared to their predecessors, its popularity fell more substantially from years 1 to 5 among recent graduates (2005-15), particularly for women (from 2.1% in year 1 to 0.8% in year 5) compared with a fall from 0.8% to 0.5% among men. The most important factor influencing dermatology choice was "hours/working conditions": in year one, 69% regarded this as important compared with 31% of those choosing other hospital physician specialties. Only 18% of respondents who chose dermatology at year 1 eventually worked in it; however, almost all practising dermatologists (94%), 10 years after qualifying, had made their future career decision by year 5. Conclusion: Dermatology is popular among female UK graduates. Most dermatologists made their career decision late but decisively. PMID- 29785181 TI - On Using a Mobile Application to Support Teledermatology: A Case Study in an Underprivileged Area in Colombia. AB - Background: The use of mobile applications in dermatology to support remote diagnosis is gaining acceptance, particularly in rural areas, where dermatology services are commonly managed by healthcare personnel with no specialty training. Moreover, ontologies-sets of concepts that represent knowledge in a given domain are increasingly being used to support medical diagnosis. A specific case is ONTODerm: an ontology to aid dermatological diagnosis. However, there is little information on the combined use of mobile applications and ontologies as support solutions in dermatology. Objective: Assessing the reliability of ONTODerm as a tool to support remote dermatological diagnosis when used together with a mobile dermatological application in underprivileged areas. Methods: A mobile application that allows characterization of skin lesions was developed, and the information about the lesions was sent to ONTODerm. An exploratory study was conducted in a remote area without access to a dermatologist. A total of 64 dermatological queries were recorded in the application and consulted with ONTODerm. Later, an experienced dermatologist evaluated the characterization and diagnosis of each query to determine the accuracy of the system. Results: The results showed that the probability of obtaining a correct diagnosis was between 64.4% and 85.6% with a confidence interval of 95%. A higher accuracy rate was obtained when the skin lesion occurred on the face or when its border was categorized as poorly demarcated. Conclusions: This study demonstrates the implementation of a teledermatology strategy based on mobile applications and domain ontology-driven knowledge base to provide timely assistance to healthcare professionals. This approach was found to be pertinent in the Colombian rural context, particularly in forest regions, where dermatology specialists are not available. The results of this article do not represent a final validation of the proposed approach; they suggest how the ontology can be improved to effectively support medical staff in marginalized regions. PMID- 29785182 TI - Reactive Oxygen Species Generation in Human Cells by a Novel Magnetic Resonance Imaging Contrast Agent. AB - The novel positive-contrast magnetic resonance imaging (MRI) marker C4 consists of an aqueous solution of cobalt chloride (CoCl2) complexed with the chelator N acetylcysteine (NAC). We evaluated whether the presence of C4 or its components would produce reactive oxygen species (ROS, including hydroxyl, peroxyl, or other reactive oxygen species) in cultured cells. Human cancer or normal cells were incubated with 1% (w/v) CoCl2.6H2O or 2% NAC or a combination of both (1% CoCl2.6H2O : 2% NAC in an aqueous solution, abbreviated as Co : NAC) in the presence or absence of H2O2. Intracellular ROS levels were measured and quantified by change in relative fluorescence units. Student's t-tests were used. In all cell lines exposed to 1000 MUM H2O2, the Co : NAC led to >=94.7% suppression of ROS at 5 minutes and completely suppressed ROS at 60 and 90 minutes; NAC suppressed ROS by >=76.6% at 5 minutes and by >=94.5% at 90 minutes; and CoCl2.6H2O suppressed ROS by >=37.2% at 30 minutes and by >=48.6% at 90 minutes. These results demonstrate that neither Co : NAC nor its components generated ROS; rather, they suppressed ROS production in cultured cells, suggesting that C4 would not enhance ROS production in clinical use. PMID- 29785183 TI - Evaluation of Reirradiation in Locally Advanced Head and Neck Cancers: Toxicity and Early Clinical Outcomes. AB - Objectives: Locoregional recurrence is the predominant pattern of treatment failure in advanced head and neck cancers. Reirradiation is a useful modality to treat inoperable head and neck cancer patients with recurrent disease. The aim of the present study was to analyze the treatment toxicity and early clinical outcomes in patients undergoing reirradiation. Methods: Twenty patients of head and neck cancers with recurrences or second cancers were evaluated. Reirradiation was done using simultaneous integrated boost volumetric modulated arc therapy (SIB VMAT), intensity modulated radiotherapy (IMRT), or conventional radiotherapy using 6MV photons. Dose prescription ranged from 30 to 60 Gy in conventional fractionation. Results: Seventeen males and three females were evaluated in this analysis. The median age of patients under study was 56.5 years. At time of analysis 8 patients (40%) had a complete response, 7 patients (35%) had progressive disease, and 25% had partial response or stable disease. Grade III-IV mucositis, dermatitis, xerostomia, dysphagia, and trismus were seen in 20%, 20%, 50%, 35%, and 45% patients, respectively, during retreatment. Patients receiving a radiotherapy dose less than 45 Gy showed a higher incidence of progressive disease (p = 0.01). The median disease-free survival for patients receiving reirradiation dose of >=46 Gy was 19 +/- 3.3 months (median +/- S Error) compared to 8 +/- 2.61 months for those with a dose prescription less than 45 Gy (p = 0.03). At 18-month follow-up 26% of patients undergoing reirradiation were disease-free. Conclusions: Our results show improved tumor control using a prescription of doses >=46 Gy in retreatment setting. PMID- 29785184 TI - TheraCal LC: From Biochemical and Bioactive Properties to Clinical Applications. AB - Background: Direct pulp capping is a popular treatment modality among dentists. TheraCal LC is a calcium silicate-based material that is designed as a direct/indirect pulp capping material. The material might be very attractive for clinicians because of its ease of handling. Unlike other calcium silicate-based materials, TheraCal LC is resin-based and does not require any conditioning of the dentine surface. The material can be bonded with different types of adhesives directly after application. There has been considerable research performed on this material since its launching; however, there are no review articles that collates information and data obtained from these studies. This review discusses the various characteristics of the material with the aim of establishing a better understanding for its clinical use. Methods: A search was conducted using search engines (PubMed and Cochrane databases) in addition to reference mining of the articles that was used to locate other papers. The process of searching for the relevant studies was performed using the keywords pulp protection, pulp capping, TheraCal, and calcium silicates. Only articles in English published in peer reviewed journals were included in the review. Conclusion: This review underlines the fact that further in vitro and in vivo studies are required before TheraCal LC can be used as a direct pulp capping material. PMID- 29785185 TI - Morphometric Analysis of the Mental Foramen Using Cone-Beam Computed Tomography. AB - This study evaluated the effects of age and sex on the location and size of the mental foramen (MF). A total of 104 cone-beam computed tomography (CBCT) scans from patients' aged 18-80 years were selected. Images were evaluated using the following parameters: position and size of the MF, and Distances A (distance from the upper limit of the MF to the apex of the first lower premolar), B (distance from the upper cortical border of the MF to the alveolar crest), and C (distance from the border of the MF to the base of the mandible). Results revealed that the location of the MF was predominantly apical (44.4%), between the long axes of the premolars, at an average distance of 4.92 mm from the root of the first lower premolar. The height of the MF was significantly different between both sexes (3.41 and 2.99 mm, resp.; mean height: 3.11 mm; P=0.003). The MF was located on average at 11.21 mm from the alveolar crest and 12.31 mm from the base of the mandible; the former measurement was significantly different between both sexes (13.13 and 11.98 mm, resp.; P <= 0.001). In conclusion, the location of the MF was predominantly apical between the long axes of the premolars, and the mean size and distance of the MF were greater in men. PMID- 29785187 TI - The association between sexual dysfunctions and severity of symptoms in patients with chronic spontaneous urticaria. PMID- 29785186 TI - Platelets activated by the anti-beta2GPI/beta2GPI complex release microRNAs to inhibit migration and tube formation of human umbilical vein endothelial cells. AB - Background: Patients with anti-beta2GPI antibodies display significantly higher platelet activation/aggregation and vascular endothelial cell damage. The mechanism underlying the correlation between platelet activation, vascular endothelial cell dysfunctions and anti-beta2GPI antibodies remains unknown. Methods: In this study, we derived miR-96 and -26a from platelets activated by the anti-beta2GPI/beta2GPI complex and explored their role in modulating human umbilical vein endothelial cell (HUVEC) migration and tube formation. Results: Anti-beta2GPI/beta2GPI complex induces the release of platelet-derived microparticles (p-MPs). The amounts of miR-96 and -26a in these p-MPs were also higher than for the control group. Co-incubation of HUVECs with p-MPs resulted in the transfer of miR-96 and -26a into HUVECs, where they inhibited migration and tube formation. The targeting role of these miRNAs was further validated by directly downregulating targeted selectin-P (SELP) and platelet-derived growth factor receptor alpha (PDGFRA) via luciferase activity assay. Conclusion: Our study suggests that miR-96 and -26a in p-MPs can inhibit HUVEC behavior by targeting SELP and PDGFRA. PMID- 29785188 TI - Electroacupuncture Ameliorates Cognitive Deficit and Improves Hippocampal Synaptic Plasticity in Adult Rat with Neonatal Maternal Separation. AB - Exposure to adverse early-life events is thought to be the risk factors for the development of psychiatric and altered cognitive function in adulthood. The purpose of this study was to investigate whether electroacupuncture (EA) treatment in young adult rat would improve impaired cognitive function and synaptic plasticity in adult rat with neonatal maternal separation (MS). Wistar rats were randomly divided into four groups: control group, MS group, MS with EA treatment (MS + EA) group, and MS with Sham-EA treatment (MS + Sham-EA) group. We evaluated the cognitive function by using Morris water maze and fear conditioning tests. Electrophysiology experiment used in vivo long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses was detected to assess extent of synaptic plasticity. Repeated EA stimulation at Baihui (GV 20) and Yintang (GV 29) during postnatal 9 to 11 weeks was identified to significantly ameliorate poor performance in behavior tests and improve the impaired LTP induction detected at Schaffer Collateral-CA1 synapse in hippocampus. Collectively, the findings suggested that early-life stress due to MS may induce adult cognitive deficit associated with hippocampus, and EA in young adult demonstrated that its therapeutic efficacy may be via ameliorating deficit of hippocampal synaptic plasticity. PMID- 29785189 TI - The Investigation of the Effect and Mechanism of Sophora moorcroftiana Alkaloids in Combination with Albendazole on Echinococcosis in an Experimental Rats Model. AB - Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically. PMID- 29785190 TI - Herbal Medicines Useful to Treat Inflammatory and Ulcerative Gastrointestinal Disorders: Preclinical and Clinical Studies. PMID- 29785191 TI - Antimalarial Activity of Stem Bark of Periploca linearifolia during Early and Established Plasmodium Infection in Mice. AB - Background: In Ethiopia, stem bark of Periploca linearifolia is used for the treatment of malaria by the local community and demonstrated antimalarial activity in vitro. Despite its in vitro antimalarial activity, no scientific study has been carried out to verify its activity in vivo. Therefore, the aim of the study was to evaluate the antimalarial activity of Periploca linearifolia stem bark extract in mice. Methods: The dried stem bark of Periploca linearifolia was extracted with 80% methanol and evaluated for its antimalarial activity on both early and established Plasmodium berghei infected mice. The extract was prepared at graded doses of 200, 400, and 600 mg/kg. Chloroquine and distilled water were administered to the positive and negative control groups, respectively. Results: The crude extract, at all tested doses, suppressed parasitemia significantly (p < 0.05) for 200 and 400 mg/kg and (p < 0.001) for 600 mg/kg. The suppression values at these doses were 56.98, 43.33, and 38.17 percent, respectively. Periploca linearifolia extract also demonstrated schizonticidal activity in the established malaria infection. Conclusion: The plant Periploca linearifolia has a promising antimalarial activity in mice, supporting its in vitro finding. Thus, it could be considered as a potential source to develop new antimalarial agent. PMID- 29785192 TI - Panax notoginseng Promotes Repair of Colonic Microvascular Injury in Sprague Dawley Rats with Experimental Colitis. AB - To investigate the therapeutic effects of PN on intestinal inflammation and microvascular injury and its mechanisms, dextran sodium sulfate- (DSS-) or iodoacetamide- (IA-) induced rat colitis models were used. After colitis model was established, PN was orally administered for 7 days at daily dosage of 1.0 g/kg. Obvious colonic inflammation and mucosal injuries and microvessels were observed in DSS- and IA-induced colitis groups. DAI scores, serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6, and TNF-alpha, and expression of Rap1GAP and TSP1 proteins in the colon were significantly higher while serum concentrations of IL-4 and IL-10 and MVD in colon were significantly lower in the colitis model groups than in the normal control group. PN promoted repair of colonic mucosal injury and microvessels, attenuated inflammation, and decreased DAI scores in rats with colitis. PN also decreased the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6, and TNF-alpha and increased the serum concentrations of IL-4 and IL-10, with the expression of Rap1GAP and TSP1 proteins in colonic mucosa being downregulated. The constituents of PN were identified with HPLC-DAD. To sum up, PN could promote repair of injuries of colonic mucosa and microvessels via downregulating VEGFA isoforms and inhibiting Rap1GAP/TSP1 signaling pathway. PMID- 29785193 TI - Gallnuts: A Potential Treasure in Anticancer Drug Discovery. AB - Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from different natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Though it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed. Objective. To evidence the traditional uses and phytochemicals and pharmacological mechanisms in anticancer aspects of gallnuts, a literature review was performed. Materials and Methods. The systematic review approach consisted of searching web based scientific databases including PubMed, Web of Science, and Science Direct. The keywords for searching include gallnut, Galla Chinensis, Rhus chinensis, Rhus potaninii, Rhus punjabensis, nutgall, gall oak, Quercus infectoria, Quercus lusitanica, and galla turcica. Two reviewers extracted papers independently to remove the papers unrelated to the anticancer properties of gallnuts. Patents, abstracts, case reports, and abstracts in symposium and congress were excluded. Results and Conclusion. As a result, 14 articles were eligible to be evaluated. It is primarily evident that gallnuts contain a number of bioactive metabolites, which account for anticancer activities. The phytochemical and pharmacological studies reviewed strongly underpin a fundamental understanding of anticancer properties for gallnuts (Galla Chinensis and Galla Turcica) and support their ongoing clinical uses in China. The further bioactive compounds screening and evaluation, pharmacological investigation, and clinical trials are expected to progress gallnut-based development to finally transform the wild medicinal gallnuts to the valuable authorized anticancer drugs. PMID- 29785194 TI - Genus Spondias: A Phytochemical and Pharmacological Review. AB - It is believed that many degenerative diseases are due to oxidative stress. In view of the limited drugs available for treating degenerative diseases, natural products represent a promising therapeutic strategy in the search for new and effective candidates for treating degenerative diseases. This review focuses on the genus Spondias which is widely used in traditional medicine for the treatment of many diseases. Spondias is a genus of flowering plants belonging to the cashew family (Anacardiaceae). This genus comprises 18 species distributed across tropical regions in the world. A variety of bioactive phytochemical constituents were isolated from different plants belonging to the genus Spondias. Diverse pharmacological activities were reported for the genus Spondias including cytotoxic, antioxidant, ulcer protective, hepatoprotective, anti-inflammatory, antiarthritic, and antidementia effects. These attributes indicate their potential to treat various degenerative diseases. The aim of this review is to draw attention to the unexplored potential of phytochemicals obtained from Spondias species, thereby contributing to the development of new therapeutic alternatives that may improve the health of people suffering from degenerative diseases and other health problems. PMID- 29785195 TI - Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation. AB - Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n = 35) and control group (n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications. PMID- 29785196 TI - A Computational Approach Using Bioinformatics to Screening Drug Targets for Leishmania infantum Species. AB - Background: The development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The antileishmanial activity of the strychnobiflavone flavonoid was recently demonstrated against Leishmania amazonensis and Leishmania infantum amastigotes and promastigotes. The biological effect of this molecule was identified due to its capacity to interfere in the parasite mitochondrial membrane; however, the underlying molecular mechanism remains unclear. Methods and Results: In this study, a computational approach using bioinformatics was performed to screen biological targets of strychnobiflavone in L. infantum. Computational programs, such as the target fishing approach and molecular docking assays, were used. Results showed that the putative pathway targeted by strychnobiflavone in L. infantum is the methylglyoxal degradation superpathway, and one hydrolase-like protein was predicted to be the molecular target of this flavonoid in the parasites. Conclusion: In this context, this study provides the basis for understanding the mechanism of action of strychnobiflavone in L. infantum and presents a strategy based on bioinformatics programs to screen targets of other molecules with biological action against distinct pathogens. PMID- 29785197 TI - Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network. AB - The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA) on the neuroendocrine-immune (NEI) network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund's adjuvant (CFA) model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli) acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed. PMID- 29785198 TI - Effects of Walking in Bamboo Forest and City Environments on Brainwave Activity in Young Adults. AB - Background. In Japan, "Shinrin-yoku" or forest bathing (spending time in forests) is a major practice used for relaxation. However, its effects on promoting human mental health are still under consideration. The objective of this study was to investigate the physiological and psychological relaxation effects of forest walking on adults. Sixty participants (50% males; 50% females) were trained to walk 15-minute predetermined courses in a bamboo forest and a city area (control). The length of the courses was the same to allow comparison of the effects of both environments. Blood pressure and EEG results were measured to assess the physiological responses and the semantic differential method (SDM) and STAI were used to study the psychological responses. Blood pressure was significantly decreased and variation in brain activity was observed in both environments. The results of the two questionnaires indicated that walking in the bamboo forest improves mood and reduces anxiety. Moreover, the mean meditation and attention scores were significantly increased after walking in a bamboo forest. The results of the physiological and psychological measurements indicate the relaxing effects of walking in a bamboo forest on adults. PMID- 29785199 TI - Physical Exercise For Parkinson's Disease: Clinical And Experimental Evidence. AB - Background: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. Objective: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD. Methods: This study is a critical review of the literature. Results: The progressive death of dopaminergic neurons in the substantia nigra is described as one of the main physiological mechanisms manifested before PD, directly interfering with motor behavior. However, PD is not only related to motor symptoms, but also to cognitive, autonomic, and mood impairments. Such effects may be attenuated by pharmacological influence, but also evidence suggests that the implementation of regular physical exercise programs may exhibit potential benefits over PD. The synthesis and expression of monoaminergic neurotransmitters can act positively on motor disorders, as well as directly or indirectly influence the neuronal plasticity of the brain, restoring neuronal pathways previously affected. Conclusion: Physical exercise contributes effectively to the treatment of PD, and can play a preventive and maintenance role of physical fitness and mental health. PMID- 29785200 TI - Comparative Study on Knowledge About Autism Spectrum Disorder Among Paediatric and Psychiatric Nurses in Public Hospitals in Kumasi, Ghana. AB - Background: Despite the existence of autism spectrum disorder in Ghana, few studies have provided the necessary information on the phenomenon. These studies have mostly focused on speech and language therapy for children and modification of classroom environment for children with autism spectrum disorder. This approach has resulted in a paucity of knowledge on nurse's knowledge of autism spectrum disorder in Ghana. Objective: The study sought to assess the knowledge of paediatric and psychiatric on autism spectrum disorder. Method: In this study, 130 paediatric and 93 psychiatric nurses sampled from five public hospitals in the Kumasi Metropolis participated in the survey. The Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire was employed to assess their knowledge of autism spectrum disorder. Results: It emerged from the study that psychiatric nurses were more knowledgeable on autism spectrum disorder than paediatric nurses in general and specifically on each of the four domains on the KCAHW questionnaire. However, the level of knowledge on autism spectrum disorder among both groups of nurses remains low. Apart from the previous encounter, there were no significant differences between paediatric and psychiatric nurses' gender, age, marital status, working experience and their knowledge. Conclusion: In view of the findings, it will be appropriate for autism spectrum disorder to be included in the clinical training curriculum as well as the continuous professional education for both paediatric and psychiatric nurses. This will go a long way in helping paediatric and psychiatric nurses to increase their knowledge of autism spectrum disorder. PMID- 29785201 TI - Speed breeding for multiple quantitative traits in durum wheat. AB - Background: Plant breeding requires numerous generations to be cycled and evaluated before an improved cultivar is released. This lengthy process is required to introduce and test multiple traits of interest. However, a technology for rapid generation advance named 'speed breeding' was successfully deployed in bread wheat (Triticum aestivum L.) to achieve six generations per year while imposing phenotypic selection for foliar disease resistance and grain dormancy. Here, for the first time the deployment of this methodology is presented in durum wheat (Triticum durum Desf.) by integrating selection for key traits, including above and below ground traits on the same set of plants. This involved phenotyping for seminal root angle (RA), seminal root number (RN), tolerance to crown rot (CR), resistance to leaf rust (LR) and plant height (PH). In durum wheat, these traits are desirable in environments where yield is limited by in season rainfall with the occurrence of CR and epidemics of LR. To evaluate this multi-trait screening approach, we applied selection to a large segregating F2 population (n = 1000) derived from a bi-parental cross (Outrob4/Caparoi). A weighted selection index (SI) was developed and applied. The gain for each trait was determined by evaluating F3 progeny derived from 100 'selected' and 100 'unselected' F2 individuals. Results: Transgressive segregation was observed for all assayed traits in the Outrob4/Caparoi F2 population. Application of the SI successfully shifted the population mean for four traits, as determined by a significant mean difference between 'selected' and 'unselected' F3 families for CR tolerance, LR resistance, RA and RN. No significant shift for PH was observed. Conclusions: The novel multi-trait phenotyping method presents a useful tool for rapid selection of early filial generations or for the characterization of fixed lines out-of-season. Further, it offers efficient use of resources by assaying multiple traits on the same set of plants. Results suggest that when performed in parallel with speed breeding in early generations, selection will enrich recombinant inbred lines with desirable alleles and will reduce the length and number of years required to combine these traits in elite breeding populations and therefore cultivars. PMID- 29785202 TI - Opto-thermoelectric nanotweezers. AB - Optical manipulation of plasmonic nanoparticles provides opportunities for fundamental and technical innovation in nanophotonics. Optical heating arising from the photon-to-phonon conversion is considered as an intrinsic loss in metal nanoparticles, which limits their applications. We show here that this drawback can be turned into an advantage, by developing an extremely low-power optical tweezing technique, termed opto-thermoelectric nanotweezers (OTENT). Through optically heating a thermoplasmonic substrate, alight-directed thermoelectric field can be generated due to spatial separation of dissolved ions within the heating laser spot, which allows us to manipulate metal nanoparticles of a wide range of materials, sizes and shapes with single-particle resolution. In combination with dark-field optical imaging, nanoparticles can be selectively trapped and their spectroscopic response can be resolved in-situ. With its simple optics, versatile low-power operation, applicability to diverse nanoparticles, and tuneable working wavelength, OTENT will become a powerful tool in colloid science and nanotechnology. PMID- 29785203 TI - Conflict and tuberculosis in Sudan: a 10-year review of the National Tuberculosis Programme, 2004-2014. AB - Background: Sudan is a fragile developing country, with a low expenditure on health. It has been subjected to ongoing conflicts ever since 1956, with the Darfur crisis peaking in 2004. The conflict, in combination with the weak infrastructure, can lead to poor access to healthcare. Hence, this can cause an increased risk of infection, greater morbidity and mortality from tuberculosis (TB), especially amongst the poor, displaced and refugee populations. This study will be the first to describe TB case notifications, characteristics and outcomes over a ten-year period in Darfur in comparison with the non-conflict Eastern zones within Sudan. Methods: A cross-sectional review of the National Tuberculosis Programme (NTP) data from 2004 to 2014 comparing the Darfur conflict zone with the non-conflict eastern zone. Results: New case notifications were 52% lower in the conflict zone (21,131) compared to the non-conflict zone (43,826). Smear-positive pulmonary TB (PTB) in the conflict zone constituted 63% of all notified cases, compared to the non-conflict zone of 32% (p < 0.001). Extrapulmonary TB (EPTB) predominated the TB notified cases in the non-conflict zone, comprising 35% of the new cases versus 9% in the conflict zone (p < 0.001). The loss to follow up (LTFU) was high in both zones (7% conflict vs 10% non conflict, p < 0.001) with a higher rate among re-treatment cases (12%) in the conflict zone. Average treatment success rates of smear-positive pulmonary TB (PTB), over ten years, were low (65-66%) in both zones. TB mortality among re treatment cases was higher in the conflict zone (8%) compared to the non-conflict zone (6%) (p < 0.001). Conclusion: A low TB case notification was found in the conflict zone from 2004 to 2014. High loss to follow up and falling treatment success rates were found in both conflict and non-conflict zones, which represents a significant public health risk. Further analysis of the TB response and surveillance system in both zones is needed to confirm the factors associated with the poor outcomes. Using context-sensitive measures and simplified pathways with an emphasis on displaced persons may increase access and case notification in conflict zones, which can help avoid a loss to follow up in both zones. PMID- 29785204 TI - Using digital health to enable ethical health research in conflict and other humanitarian settings. AB - Conducting research in a humanitarian setting requires quantifiable quality measures to ensure ethical study conduct. Digital health technologies are proven to improve research study quality and efficacy via automated data collection, improvement of data reliability, fidelity and resilience and by improved data provenance and traceability. Additionally, digital health methodologies can improve patient identity, patient privacy, study transparency, data sharing, competent informed consent, and the confidentiality and security of humanitarian operations. It can seem counterintuitive to press forward aggressively with digital technologies at a time of heightened population vulnerability and cyber security concerns, but new approaches are essential to meet the rapidly increasing demands of humanitarian research. In this paper we present the case for the digital modernization of humanitarian research in conflict and other humanitarian settings as a vehicle for improved research quality and ethics. PMID- 29785205 TI - Continuous succinic acid fermentation by Actinobacillus succinogenes in a packed bed biofilm reactor. AB - Background: Succinic acid is one of the most interesting platform chemicals that can be produced in a biorefinery approach. In this study, continuous succinic acid production by Actinobacillus succinogenes fermentation in a packed-bed biofilm reactor (PBBR) was investigated. Results: The effects of the operating conditions tested, dilution rate (D), and medium composition (mixture of glucose, xylose, and arabinose-that simulate the composition of a lignocellulosic hydrolysate)-on the PBBR performances were investigated. The maximum succinic acid productivity of 35.0 g L-1 h-1 and the maximum SA concentration were achieved at a D = 1.9 h-1. The effect of HMF and furfural on succinic acid production was also investigated. HMF resulted to reduce succinic acid production by 22.6%, while furfural caused a reduction of 16% in SA production at the same dilution rate. Conclusion: Succinic acid production by A. succinogenes fermentation in a packed-bed reactor (PBBR) was successfully carried out for more than 5 months. The optimal results were obtained at the dilution rate 0.5 h-1: 43.0 g L-1 of succinic acid were produced, glucose conversion was 88%; and the volumetric productivity was 22 g L-1 h-1. PMID- 29785206 TI - Life cycle assessment of residual lignocellulosic biomass-based jet fuel with activated carbon and lignosulfonate as co-products. AB - Background: Bio-jet fuels are emerging as a valuable alternative to petroleum based fuels for their potential for reducing greenhouse gas emissions and fossil fuel dependence. In this study, residual woody biomass from slash piles in the U.S. Pacific Northwest is used as a feedstock to produce iso-paraffinic kerosene, through the production of sugar and subsequent patented proprietary fermentation and upgrading. To enhance the economic viability and reduce the environmental impacts of iso-paraffinic kerosene, two co-products, activated carbon and lignosulfonate, are simultaneously produced within the same bio-refinery. A cradle-to-grave life cycle assessment (LCA) is performed for the residual woody biomass-based bio-jet fuel and compared against the cradle-to-grave LCA of petroleum-based jet fuel. This paper also discusses the differences in the environmental impacts of the residual biomass-based bio-jet fuel using two different approaches, mass allocation and system expansion, to partition the impacts between the bio-fuel and the co-products, which are produced in the bio refinery. Results: The environmental assessment of biomass-based bio-jet fuel reveals an improvement along most critical environmental criteria, as compared to its petroleum-based counterpart. However, the results present significant differences in the environmental impact of biomass-based bio-jet fuel, based on the partitioning method adopted. The mass allocation approach shows a greater improvement along most of the environmental criteria, as compared to the system expansion approach. However, independent of the partitioning approach, the results of this study reveal that more than the EISA mandated 60% reduction in the global warming potential could be achieved by substituting petroleum-based jet fuel with residual woody biomass-based jet fuel. Converting residual woody biomass from slash piles into bio-jet fuel presents the additional benefit of avoiding the impacts of slash pile burning in the forest, which results in a net negative impact on 'Carcinogenics' and 'Respiratory effects', and substantial reduction in the 'Smog' and 'Ecotoxicity' impacts. The production of woody biomass-based bio-jet fuel, however, did not show any significant improvement in the 'Acidification' and 'Eutrophication' impact categories. Conclusions: The study reveals that residual woody biomass recovered from slash piles represents a more sustainable alternative to petroleum for the production of jet fuel with a lower impact on global warming and local pollution. Future research should focus on the optimization of chemical processes of the bio-refinery to reduce the impacts on the 'Acidification' and 'Eutrophication' impact categories. PMID- 29785207 TI - Promiscuous activities of heterologous enzymes lead to unintended metabolic rerouting in Saccharomyces cerevisiae engineered to assimilate various sugars from renewable biomass. AB - Background: Understanding the global metabolic network, significantly perturbed upon promiscuous activities of foreign enzymes and different carbon sources, is crucial for systematic optimization of metabolic engineering of yeast Saccharomyces cerevisiae. Here, we studied the effects of promiscuous activities of overexpressed enzymes encoded by foreign genes on rerouting of metabolic fluxes of an engineered yeast capable of assimilating sugars from renewable biomass by profiling intracellular and extracellular metabolites. Results: Unbiased metabolite profiling of the engineered S. cerevisiae strain EJ4 revealed promiscuous enzymatic activities of xylose reductase and xylitol dehydrogenase on galactose and galactitol, respectively, resulting in accumulation of galactitol and tagatose during galactose fermentation. Moreover, during glucose fermentation, a trisaccharide consisting of glucose accumulated outside of the cells probably owing to the promiscuous and transglycosylation activity of beta glucosidase expressed for hydrolyzing cellobiose. Meanwhile, higher accumulation of fatty acids and secondary metabolites was observed during xylose and cellobiose fermentations, respectively. Conclusions: The heterologous enzymes functionally expressed in S. cerevisiae showed promiscuous activities that led to unintended metabolic rerouting in strain EJ4. Such metabolic rerouting could result in a low yield and productivity of a final product due to the formation of unexpected metabolites. Furthermore, the global metabolic network can be significantly regulated by carbon sources, thus yielding different patterns of metabolite production. This metabolomic study can provide useful information for yeast strain improvement and systematic optimization of yeast metabolism to manufacture bio-based products. PMID- 29785208 TI - Developing cellulolytic Yarrowia lipolytica as a platform for the production of valuable products in consolidated bioprocessing of cellulose. AB - Background: Both industrial biotechnology and the use of cellulosic biomass as feedstock for the manufacture of various commercial goods are prominent features of the bioeconomy. In previous work, with the aim of developing a consolidated bioprocess for cellulose bioconversion, we conferred cellulolytic activity of Yarrowia lipolytica, one of the most widely studied "nonconventional" oleaginous yeast species. However, further engineering this strain often leads to the loss of previously introduced heterologous genes due to the presence of multiple LoxP sites when using Cre-recombinase to remove previously employed selection markers. Results: In the present study, we first optimized the strategy of expression of multiple cellulases and rescued selection makers to obtain an auxotrophic cellulolytic Y. lipolytica strain. Then we pursued the quest, exemplifying how this cellulolytic Y. lipolytica strain can be used as a CBP platform for the production of target products. Our results reveal that overexpression of SCD1 gene, encoding stearoyl-CoA desaturase, and DGA1, encoding acyl CoA:diacylglycerol acyltransferase, confers the obese phenotype to the cellulolytic Y. lipolytica. When grown in batch conditions and minimal medium, the resulting strain consumed 12 g/L cellulose and accumulated 14% (dry cell weight) lipids. Further enhancement of lipid production was achieved either by the addition of glucose or by enhancing cellulose consumption using a commercial cellulase cocktail. Regarding the latter option, although the addition of external cellulases is contrary to the concept of CBP, the amount of commercial cocktail used remained 50% lower than that used in a conventional process (i.e., without internalized production of cellulases). The introduction of the LIP2 gene into cellulolytic Y. lipolytica led to the production of a strain capable of producing lipase 2 while growing on cellulose. Remarkably, when the strain was grown on glucose, the expression of six cellulases did not alter the level of lipase production. When grown in batch conditions on cellulose, the engineered strain consumed 16 g/L cellulose and produced 9.0 U/mL lipase over a 96-h period. The lipase yield was 562 U lipase/g cellulose, which represents 60% of that obtained on glucose. Finally, expression of the hydroxylase from Claviceps purpurea (CpFAH12) in cellulolytic Y. lipolytica procured a strain that can produce ricinoleic acid (RA). Using this strain in batch cultures revealed that the consumption of 11 g/L cellulose sustained the production of 2.2 g/L RA in the decane phase, 69% of what was obtained on glucose. Conclusions: In summary, this study has further demonstrated the potential of cellulolytic Y. lipolytica as a microbial platform for the bioconversion of cellulose into target products. Its ability to be used in consolidated process designs has been exemplified and clues revealing how cellulose consumption can be further enhanced using commercial cellulolytic cocktails are provided. PMID- 29785209 TI - Acute suppurative thyroiditis caused by thyroid papillary carcinoma in the right thyroid lobe of a healthy woman. AB - Background: The thyroid gland is resistant to microbial infection, because of its organ characteristics such as encapsulation, iodine content, and rich blood supply. Therefore, acute suppurative thyroiditis (AST), as a bacterial infection of the thyroid gland, is rarely seen. AST typically takes places on the left side the neck region in children, because of the coincidence of the left piriform sinus fistula, as a most common route of infection. AST is also usually seen in immunocompromised hosts. Herein, we report a rare case of AST in the right thyroid lobe of adult woman without any immunocompromised condition. Case presentation: A 59-year-old woman was introduced to our hospital for the further examination with fever, sore throat, and right anterior neck swelling. The patient appeared not to be immunodeficient. Neck ultrasonography showed a 47-mm, hypoechoic, heterogeneous nodule with ill-defined margins and irregular form, suggesting a right thyroid malignant nodule. Fine needle aspiration (FNA) biopsy specimen revealed numerous number of neutrophils in the background without nuclear atypia. Based on the clinical course and cytology, AST was confirmed to be diagnosed. Complete response was obtained by an intravenous administration of antimicrobial agents within a week. Image findings such as CT scan did not show any piriform sinus fistula. Four months later, neck ultrasonography showed a significant decrease in size of the nodule in the right thyroid gland to 27 mm, but the lesion still resembled a malignant nodule. So, FNA was repeated again and cytological examination confirmed papillary thyroid carcinoma (PTC). The patient subsequently underwent total thyroidectomy and bilateral level D1 lymph node dissection. Histological findings revealed a 20-mm PTC in the right lobe with sternothyroid muscle invasion of the tumor. Conclusions: This report represents a rare case of AST associated with PTC on the right side of thyroid gland, found in a healthy adult woman. The reason why AST coincided with malignant thyroid tumor is unclear. We have to take it into our account that malignant tumor may exist in the background when AST is identified on the right side of thyroid gland with a healthy subject. PMID- 29785211 TI - A Very Rare Cause of Lower Limb Ischemia in Young People: Popliteal Artery Entrapment. AB - Background: Popliteal artery entrapment syndrome (PAES) is a very rare pathology that can cause lower extremity ischemia in healthy young people. Anomalous anatomic relationships between the popliteal artery (PA) and the surrounding musculo-tendinous structures cause PAES. We present 31 patients with PAES in 35 limbs that were treated surgically in our clinic within a 12-year period. Patients and Methods: From 2001 to 2015, 31 patients (mean age: 32 +/- 7.4 years) underwent surgery for PAES. ; 4 patients presented had bilateral PAES. Doppler ultrasonography (US), magnetic resonance angiography (MRA), and conventional angiography were performed as diagnostic procedures. We detected Type I PAES in 4 limbs and Type II PAES in 12 limbs. In the remaining 19 limbs, we diagnosed Type III or Type IV PAES. Simple release of the PA, PA embolectomy and simple release, and the radial artery (RA) patch angioplasty, with or without thromboendarterectomy (TEA), were performed. In 12 limbs, PA continuity was provided by RA interposition. Results: With the exception of 5 patients, no complications were seen after surgery. Haematoma was detected in 2 patients and local infection in 2 patients. One patient required a revision for recurrent PA thromboembolic event 12 h after surgery. At a median follow- up of 23 months (range: 11-29 months), there were no postoperative complications. Conclusions: PAES can result in lower limb ischemia due to chronic vascular trauma in young healthy patients. The use of diagnostic tools such as US, a non-invasive method, and MRA are effective diagnostic tools for early diagnosis. With their combined approach, exact and early diagnosis can be achieved. PA release, alone or with arterial bypass using RA, is a viable treatment option when intervention is necessary to prevent limb loss in the early stages of the disease. PMID- 29785210 TI - Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus. AB - Background: Adipokines are involved in the pathogenesis of metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). This study investigates the levels of leptin, resistin, visfatin, secreted frizzled-related protein 5 (SFRP5), monocyte chemoattractant protein-1 (MCP-1) and retinol-binding protein 4 (RBP4) and their correlations with clinical parameters of overweight and T2DM. Methods: We recruited overweight 50 patients with T2DM, 88 non-overweight patients with T2DM, 29 overweight and 100 non-overweight individuals devoid of T2DM for this study. The levels of studied adipokines were measured by enzyme linked immunosorbent assay and correlated with clinical parameters. Results: The levels of MCP-1 and SFRP5 were decreased while visfatin and RBP4 levels were increased in patients with T2DM compared to those in the control individuals (P < 0.01). Among patients with T2DM, leptin and resistin levels were higher while RBP4 levels were lower in patients with overweight T2DM compared to those in patients with non-overweight T2DM (P < 0.0001, 0.019 and 0.05, respectively). Leptin and MCP-1 levels were correlated with HOMA-IR, QUICKI and HOMA-beta. Leptin/MCP-1 ratio was correlated with insulin levels, HOMA-IR and HOMA-beta indexes. Resistin/RBP4, visfatin/MCP-1 and MCP-1/RBP4 ratios were strongly correlated with the levels of fasting glucose, HbA1c and HOMA-beta. In addition, ROC curve analyses indicated a diagnostic potential of resistin/RBP4 and MCP 1/RBP4 indexes for T2DM (AUC = 0.81 and 0.83, respectively) and beta-cell function (AUC = 0.76 and 0.74, respectively). Conclusions: Adipokines (leptin, resistin, visfatin, SFRP5, MCP-1, and RBP4) are associated with overweight and T2DM and may serve as a potential prognostic marker and therapeutic intervention for overweight-related T2DM. PMID- 29785213 TI - A Case Series and Review of Bacillus Cereus Endocarditis from India. AB - Introduction: Bacillus cereus is a gram positive bacilli found commonly in the soil and environment. It is a bacteria rarely associated with endocarditis. Case History: Intravenous drug abuse, presence of valvular defects, pacemakers, immunodeficiency are some of the known risk factors for B.cereus endocarditis. We present here a case series of two patients with B.cereus endocarditis along with a review of the literature. Conclusion: This is the first report of B.cereus endocarditis from India to the best of our knowledge. PMID- 29785212 TI - Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events? AB - Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s' and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1beta with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy. PMID- 29785214 TI - Etiological Trends and Patterns of Antimicrobial Resistance in Respiratory Infections. AB - Background: Respiratory infections are one of the commonest causes of morbidity and mortality related to infectious diseases worldwide. The emergence of antimicrobial resistance is a major global health problem which is well established in developing countries. Good clinical suspicion and correct laboratory identification of respiratory infection causing organisms followed by the appropriate management are needed to compact both community-acquired and nosocomial infection respiratory infections. Objectives: A retrospective study was carried out to elucidate the etiology of respiratory infections in Sudan, as well as to guide the physician to the best antimicrobial alternatives used in the treatment of respiratory infection. Method: Respiratory isolates that have been morphologically identified and biologically characterized were subjected to antibiotic susceptibility testing. Results: A total of 1481 respiratory specimens were examined, recovering 377 organisms from 350 culture positive samples [225(59.7%) sputum, 94(24.9%) broncho-alveolar lavage (BAL), 58(15.4%) Pleural fluid], the commonest organisms were Klebsiella ssp. (25.20%) and mycobacterium tuberculosis (25.20%), followed by Staphylococcus aureus(19.89%) and Pseudomonas aeruginosa(8.49%). High rate of resistance of bacterial isolates was observed to Co-trimoxazole (BA), Ampicillin sulbactam (AS), Cefotaxime (CF) and Tetracycline (TE), being 80%, 72.3%, 68.8% and 66.9% respectively; on the other hand, very low resistance rate was found to Amikacin (AK) and Levofloxacin (LE), being 4.6% and 8.5%, respectively. Conclusion: Guided prescription of antimicrobial agents must be implemented and controlled to limit further spread of antimicrobial resistance. PMID- 29785216 TI - Staphylococcus Aureus Surface Protein G is An Immunodominant Protein and a Possible Target in An Anti-Biofilm Drug Development. AB - Background: Staphylococcus aureus is a Gram-positive bacterium that causes severe illnesses in the human population. The capacity of S. aureus strains to form biofilms on biotic and abiotic surfaces creates serious problems for treatment of hospital infections and has stimulated efforts to develop new means of specific protection or immunotherapy. Material and Methods: We found that rabbit serum raised against crude concentrated S. aureus liquid culture significantly decreased the development of staphylococcal biofilm in vitro. To discover the corresponding staphylococcal antigen, we used mass-spectrometry and molecular cloning and identified three major immunodominant proteins. They included alpha haemolysin, serine proteinase SplB and S. aureus surface protein G, known as adhesin SasG. Results: Although according to literature data, all these proteins represent virulence factors of S. aureus and play diverse and important roles in the pathogenesis of staphylococcal diseases, only SasG can be directly implicated into the biofilm formation because of its surface location on a staphylococcal cell. Indeed, rabbit serum directed against purified recombinant SasG, similar to serum against crude staphylococcal liquid culture, prevented the formation of a biofilm. Conclusion: SasG can be considered as a target in an anti-biofilm drug development and a component of the vaccine or immunotherapeutic preparations directed against staphylococcal infections in humans. PMID- 29785215 TI - Mycobacteriosis and Tuberculosis: Laboratory Diagnosis. AB - Background: Tuberculosis is one of the most important infectious diseases that has claimed its victims throughout much of known human history. With Koch's discovery of the tubercle bacillus as the etiologic agent of the disease, his sanitary and hygienic measures, which were based on his discovery and the development of a vaccine against tuberculosis by Albert Calmette and Camille Guerin in 1921, an attenuated Mycobacterium bovis strain, bacilli Calmette-Guerin (BCG), and the discovery of the first antibiotic against tuberculosis, streptomycin by Selman Waksman in 1943, soon led to the opinion that appropriate control measures had become available for tuberculosis and it had been assumed that the disease could ultimately be eradicated.The emergence of resistant strains of this bacteria and widespread distribution of the disease in the world, and the emergence of the AIDS epidemic destroyed any possibility of global control of tuberculosis in the foreseeable future. Objectives: The purpose of this review is to highlight the current scientific literature on mycobacterial infections and provide an overview on the laboratory diagnosis of tuberculosis and non-tuberculosis infections based on conventional phenotypic and modern molecular assays. Method: In this study, a number of 65 papers comprising 20 reviews, 9 case reports, and 36 original research in association with mycobacteriosis and the laboratory diagnosis of mycobacterial infections, were reviewed. Results: Based on our analysis on the published documents methods applied for the laboratory diagnosis of tuberculosis are continually assessed and developed in order to achieve more rapid, less expensive, and accurate results. Acid-fast staining and culture for mycobacteria remain at the core of any diagnostic algorithm with the sensitivity of 20-70% and specificity of 95-98% for AFB microscopy and the sensitivity of 95% and the specificity of 98% for culture based diagnosis. Following growth in culture, molecular tests such as nucleic acid hybridization probes and DNA sequencing may be used for definitive species identification. Nucleic acid amplification methods provide the means for direct detection of Mycobacterium tuberculosis in respiratory specimens without the prerequisite to isolate or culture the organism, leading to more rapid diagnosis and better patient care. Conclusion: As the researchers in a developing country, we strongly believe that despite significant advances in laboratory capacity, in many countries reliable confirmation of suspected mycobacterial diseases is hindered by a lack of knowledge on proper standardized methods, sufficient funds, suitably trained staff and laboratory supplies. PMID- 29785217 TI - Expression of Phi11 Gp07 Causes Filamentation in Escherichia coli. AB - Background: The Gp07 protein of aureophage Phi11 exhibits growth inhibitory effects when overexpressed in E. coli .The protein harbors two domains- an amino terminal Bro-like domain and a carboxy terminal Ant superfamily like KilA domain, of which the KilA domain retains the growth inhibitory effect of Gp07. Methods: We studied the effects exerted by the overexpression of Gp07 and its separate domains upon the growth rate as well as the morphology of the E. coli cells. Additionally, we generated a mutant of Gp07 (designated as DeltaGp07) by deleting the first eleven amino acid residues from the amino-terminal region of Gp07, and studied its growth inhibitory effects upon E. coli. Results: Our results indicate that Gp07, DeltaGp07 as well as the Carboxy-terminal region of Gp07 upon overexpression, retards the growth rate of the E. coli cells and also induces filamentation in the cells. Surprisingly, our data clearly suggests that the growth inhibition and filamentation induced by the the amino-terminal domain of Gp07 is temporal in nature. Conclusion: The carboxy-terminal of domain of gp07 is essential for its activity. PMID- 29785218 TI - Molecular Study of Quinolone Resistance Determining Regions of gyrA Gene and parC Genes in Clinical Isolates of Acintobacter baumannii Resistant to Fluoroquinolone. AB - Introduction: Acinetobacterb aumannii (A. baumannii) is an important pathogen in health care associated infections. Quinolone resistance has emerged in this pathogen. Aims & Objectives: The aim of the present study was to determine the presence of mutations of gyrA gene and parC genes by Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP-PCR) among clinical isolates of A. baumanii. Materials and Methods: The study was carried out on 140 clinical isolates of A. baumannii. The isolates were subjected to molecular study of mutations of gyrA gene and parC genes by RFLP-PCR beside determination of Minimal Inhibitory Concentration (MIC) by macro dilution tube method. Results: The isolates of A. baumannii were resistant to ciprofloxacine and levofloxacin at MIC >4 ug/ml. The most isolates had MIC >128 ug/ml (42.3%). All resistant strains to ciprofloxacin of A. baumannii had mutations in gyrA and parC. The most frequent mutations were combined mutations in both genes (85.5%) and 5% had single mutation either in gyrA or parC. The most frequently combined mutations were associated with MIC >128 ug/ml (42.3%). Conclusion: From this study we can conclude that resistance to ciprofloxacin was common in clinical isolates of A. baumannii. The most frequent mutations were present in gyrA and parC. However, mutations in parC alone were not uncommon. Further large scale studies are required to elucidate the resistance pattern of A. baumannii and its molecular mechanisms. PMID- 29785219 TI - Assessing Methanogenic Archaeal Community in Full Scale Anaerobic Sludge Digester Systems in Dubai, United Arab Emirates. AB - Introduction: Anaerobic digestion for methane production comprises of an exceptionally diverse microbial consortium, a profound understanding about which is still constrained. In this study, the methanogenic archaeal communities in three full-scale anaerobic digesters of a Municipal Wastewater Treatment Plant were analyzed by Fluorescence in situ hybridization and quantitative real-time Polymerase Chain Reaction (qPCR) technique. Methods & Materials: Fluorescence in situ hybridization (FISH) was performed to detect and quantify the methanogenic Archaea in the sludge samples whereas qPCR was carried out to support the FISH analysis. Multiple probes targeting domain archaea, different orders and families of Archaea were used for the studies. Results and Discussion: In general, the aceticlastic organisms (Methanosarcinaceae & Methanosaetaceae) were more abundant than the hydrogenotrophic organisms (Methanobacteriales, Methanomicrobiales, Methanobacteriaceae & Methanococcales). Both FISH and qPCR indicated that family Methanosaetaceae was the most abundant suggesting that aceticlastic methanogenesis is probably the dominant methane production pathway in these digesters. Conclusion: Future work involving high-throughput sequencing methods and correlating archaeal communities with the main operational parameters of anaerobic digesters will help to obtain a better understanding of the dynamics of the methanogenic archaeal community in wastewater treatment plants in United Arab Emirates (UAE) which in turn would lead to improved performance of anaerobic sludge digesters. PMID- 29785220 TI - Physicochemical and Microbiological Qualities' Assessment of Popular Bangladeshi Mango Fruit Juice. AB - Introduction: Mango juice has always been considered as a delicious, nutritious popular drink, but processed juice may not always be safe due to chemical and microbial risks. Determination of physicochemical and microbiological qualities of some packed mango juices of Bangladesh will help consumers to know the present scenario. Material and Methods: Six commercially available different juice samples were collected from the market. Carbohydrate profiles were determined using HPLC, crude protein content was calculated using the Kjeldahl method and other parameters were determined by standard AOAC methods. Standard culture techniques were followed to assess the total viable count (TVC), E. coli and other fecal coliforms. Results: The highest quantity of monosaccharide (58.88%) was recorded in the AC1ME5 brand, while the lowest in Homemade (5.648%) and MN1GL2 (9.867%). The maximum content of acidity recorded was 0.24% and minimum 0.21%. The TSS content of all samples varied from 19% to 12%. The highest quantity 6.87% and the lowest 3.62% of reducing sugar were recorded. Most of the mango juices were low in protein and very low/negligible in fat content. Total viable count of different types of fruit juices varied from 1*103 - 3*103 CFU/ml. No significant amount of E. coli and fecal coliform was detected. Conclusion: It can be concluded that the locally available mango juices contain a safe level of nutritional and microbial elements for human consumption, but not highly satisfactory. PMID- 29785221 TI - CoCrMo alloy vs. UHMWPE Particulate Implant Debris Induces Sex Dependent Aseptic Osteolysis Responses In Vivo using a Murine Model. AB - Background: The rate of revision for some designs of total hip replacements due to idiopathic aseptic loosening has been reported as higher for women. However, whether this is environmental or inherently sex-related is not clear. Objective: Can particle induced osteolysis be sex dependent? And if so, is this dependent on the type of implant debris (e.g. metal vs polymer)? The objective of this study was to test for material dependent inflammatory osteolysis that may be linked to sex using CoCrMo and implant grade conventional polyethylene (UHMWPE), using an in vivo murine calvaria model. Methods: Healthy 12 week old female and male C57BL/6J mice were treated with UHMWPE (1.0um ECD) or CoCrMo particles (0.9um ECD) or received sham surgery. Bone resorption was assessed by micro-computed tomography, histology and histomorphometry on day 12 post challenge. Results: Female mice that received CoCrMo particles showed significantly more inflammatory osteolysis and bone destruction compared to the females who received UHMWPE implant debris. Moreover, females challenged with CoCrMo particles exhibited 120% more inflammatory bone loss compared to males (p<0.01) challenged with CoCrMo implant debris (but this was not the case for UHMWPE particles). Conclusion: We demonstrated sex-specific differences in the amount of osteolysis resulting from CoCrMo particle challenge. This suggests osteo-immune responses to metal debris are preferentially higher in female compared to male mice, and supports the contention that there may be inherent sex related susceptibility to some types of implant debris. PMID- 29785222 TI - Proximal Femoral Bone Regeneration After an Uncemented Hydroxyapatite-coated Long stem in Revision Hip Surgery. AB - Background: Bone remodelling with lateral femoral cortex thinning is a major concern after extensively porous-coated long-stem in revision surgery. Extensive hydroxyapatite coated long-stems were introduced to improve osseointegration, but bone remodelling changes have not been quantified. Objective: The question of whether bone remodelling changes from extensive hydroxyapatite-coated long stems influence the durability of femoral revision, clinical outcome is assessed in follow-up radiographs. Methods: Uncemented straight monoblock hydroxyapatite coated long-stems used in revision hip surgery for aseptic loosening were assessed in a consecutive series of 64 hips (60 patients). Mean follow-up was 8.6 years and the mean age at surgery was 70 years (27-91). The pre-operative bone defect was classified according to Paprosky. Cortical struts were not used in this series. Cortical index and femoral cortical width were measured at three different levels at different periods. Results: Four patients with pain under level 4 due to stem loosening needed an exchange surgery of their femoral component, but two patients rejected re-surgery. The cumulative probability of not having aseptic loosening was 91.2% (95% confidence interval 73.5-96.9) at 10 years according to Kaplan and Meier. Twenty-seven of 35 osteolytic lesions had disappeared or decreased at the last follow-up. The thickness of the lateral and medial cortex increased over the course of the study at different levels. Increases of femoral cortex thickness were greater in men and in cases with mild bone defects. Conclusion: Although clinical outcome of the hydroxyapatite-coated long stem in revision surgery is good but not outstanding, most osteolytic lesions heal and the femoral cortex thickness increases at different levels. PMID- 29785223 TI - Complications of the Fingers and Hand After Arthroscopic Rotator Cuff Repair. AB - Background: Complications of the fingers and hand that occur after Arthroscopic Rotator Cuff Repair (ARCR) have not been examined in detail. Objective: The aim of our study was to evaluate the diagnosis and treatment of complications of the fingers and hand that occur after ARCR and to examine treatment outcomes. Methods: The case records of 40 patients (41 shoulders) who underwent ARCR using suture anchors were retrospectively reviewed to investigate complications of the fingers and hand after ARCR. Results: Twelve patients (29%) experienced numbness, pain, edema, and movement limitations of the fingers and hand. These symptoms occurred on average 1.1 months (range, 0.1-2.5 months) after ARCR. The diagnoses were cubital tunnel syndrome in 2 hands, carpal tunnel syndrome in 3 hands, and flexor tenosynovitis (TS) in 10 hands. None of the 10 hands with TS exhibited triggering of the fingers. The mean interval between treatment initiation and symptom resolution was 2.2 months for the 5 hands treated by corticosteroid injection or surgery and 5.9 months for the 7 hands treated by alternating warm and cold baths alone. None of the hands exhibited Complex Regional Pain Syndrome (CRPS). Conclusion: Complications of the fingers and hand after ARCR were observed in 29%. TS was the most frequent complication. When symptoms in the fingers and hand occur after ARCR, rather than immediately suspecting CRPS, TS should be primarily suspected, including when TS symptoms such as triggering are not present, and these patients should be treated proactively using corticosteroid injections or surgery. PMID- 29785224 TI - Pseudarthrosis of the Calcaneus: Advantages of Regenerative Medicine in the Management of a Rare Entity, A Case Report and Review of Literature. AB - Background: The follow-up of calcaneal fractures has shown that they are difficult to manage and lead to multiple complications such as malunion and subtalar osteoarthritis. Pseudarthrosis of the calcaneus is an extremely rare complication, which was described in the literature through case reports.In the existing literature, only seven studies, including thirteen patients have reported the nonunion. However, to the best of our knowledge, no study elucidates the role of new techniques of regenerative medicine such as Bone Marrow Concentrates (BMC) or Platelet Rich Plasma (PRP) in the management. Methods: We report a case of a patient with a pseudarthrosis after a calcaneal fracture treated with BMC injection in the non-union site, without the need for surgical approach. Results: Four months after treatment, the patient was ambulant without support and was completely pain-free. Moreover, after one year the radiological follow up by CT scan showed a satisfactory filling of the non union. Conclusion: In one case, we try to highlight the advantage of our therapeutic alternatives, which are having a good union while avoiding the complications of surgical approaches and without sacrificing the subtalar joint when it is possible. PMID- 29785225 TI - Bipolar Dislocation of the Arm (Shoulder And Elbow): About One Case in an African Teaching Hospital. AB - We report an exceptional clinical case of an ipsilateral dislocation fracture of the shoulder and right elbow, realizing a "swinging arm". Following a violent road accident, patient S.I, a 43-year-old left-handed sports educator, presented with an antero-medial shoulder dislocation fracture and a posterolateral ipsilateral elbow fracture-dislocation. The reduction in urgency, followed by the orthopedic compression by Mayo Clinic and functional rehabilitation, allowed obtaining a good result after seven months. The ipsilateral bipolar dislocation of the shoulder and elbow is an exceptional lesional entity. Its adequate care in emergency makes it possible to obtain good anatomical and functional results. PMID- 29785226 TI - Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke. AB - Background: Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (<= 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Methods and materials: Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Results: Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. Conclusion: The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke. PMID- 29785227 TI - Alterations in the Three Components of Selfhood in Persons with Post-Traumatic Stress Disorder Symptoms: A Pilot qEEG Neuroimaging Study. AB - Background and Objective: Understanding how trauma impacts the self-structure of individuals suffering from the Post-Traumatic Stress Disorder (PTSD) symptoms is a complex matter and despite several attempts to explain the relationship between trauma and the "Self", this issue still lacks clarity. Therefore, adopting a new theoretical perspective may help understand PTSD deeper and to shed light on the underlying psychophysiological mechanisms. Methods: In this study, we employed the "three-dimensional construct model of the experiential selfhood" where three major components of selfhood (phenomenal first-person agency, embodiment, and reflection/narration) are related to three Operational Modules (OMs) of the self referential brain network. These modules can be reliably estimated through operational synchrony analysis of the Electroencephalogram (EEG). Six individuals with PTSD symptoms and twenty-nine sex-, age- and demographic- (race, education, marital status) matched healthy controls underwent resting state EEG signal acquisition with the following estimation of the synchrony strength within every OM. Results: Our results indicate that subjects with PTSD symptoms had significantly stronger EEG operational synchrony within anterior and right posterior OMs as well as significantly weaker EEG operational synchrony within left posterior OM compared to healthy controls. Moreover, increased the functional integrity of the anterior OM was positively associated with hyperactivity symptoms, reduced synchrony of the left posterior OM was associated with greater avoidance, and increased right posterior OM integrity was positively correlated with intrusion and mood symptoms. Conclusion: The results are interpreted in light of the triad model of selfhood and its theoretical and clinical implications (including a new treatment approach) are discussed. PMID- 29785228 TI - Evaluating the Utility of a Structured Clinical Protocol for Reducing the Impact of Behavioural and Psychological Symptoms of Dementia in Progressive Neurological Diseases: A Pilot Study. AB - Objectives: Behavioural and psychological symptoms of dementia (BPSD) cause significant distress to both aged care residents and staff. Despite the high prevalence of BPSD in progressive neurological diseases (PNDs) such as multiple sclerosis, Huntington's disease, and Parkinson's disease, the utility of a structured clinical protocol for reducing BPSD has not been systematically evaluated in PND populations. Method: Staff (n = 51) and individuals with a diagnosis of PND (n = 13) were recruited into the study, which aimed to evaluate the efficacy of a PND-specific structured clinical protocol for reducing the impact of BPSD in residential aged care (RAC) and specialist disability accommodation (SDA) facilities. Staff were trained in the clinical protocol through face-to-face workshops, which were followed by 9 weeks of intensive clinical supervision to a subset of staff ("behaviour champions"). Staff and resident outcome measures were administered preintervention and immediately following the intervention. The primary outcome was frequency and severity of BPSD, measured using the Neuropsychiatric Inventory-Nursing Home Version (NPI NH). The secondary outcome was staff coping assessed using the Strain in Dementia Care Scale (SDCS). Results: In SDA, significant reductions in staff ratings of job-related stress were observed alongside a statistically significant decrease in BPSD from T1 to T2. In RAC, there was no significant time effect for BPSD or staff coping; however, a medium effect size was observed for staff job stress. Conclusions: Staff training and clinical support in the use of a structured clinical protocol for managing BPSD were linked to reductions in staff job stress, which may in turn increase staff capacity to identify indicators of resident distress and respond accordingly. Site variation in outcomes may relate to organisational and workforce-level barriers that may be unique to the RAC context and should be systematically addressed in future RCT studies of larger PND samples. PMID- 29785229 TI - The Circular RNA hsa_circ_0001445 Regulates the Proliferation and Migration of Hepatocellular Carcinoma and May Serve as a Diagnostic Biomarker. AB - Circular RNAs (circRNA), a class of noncoding RNAs, have been found to be involved in various diseases. Here, the expression levels of the circRNA hsa_circ_0001445 in 73 pairs of hepatocellular carcinoma (HCC) and adjacent nontumor tissues were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Our data demonstrate that the hsa_circ_0001445 levels were significantly decreased in HCC tissues (P < 0.001) and markedly associated with the number of tumor foci (P = 0.014). Furthermore, in vitro approaches showed that overexpression of hsa_circ_0001445 promoted apoptosis and inhibited proliferation, migration, and invasion of HCC-derived cells, suggesting that hsa_circ_0001445 might be involved in the development of HCC. In addition, we found that the plasma hsa_circ_0001445 transcription levels in HCC patients were lower than those in cirrhosis (P < 0.001) and hepatitis B (P < 0.001) patients as well as in healthy controls (P < 0.001). In fact, receiver operating characteristic curve analysis indicated that plasma hsa_circ_0001445 could be a fairly accurate marker to distinguish HCC cases from healthy controls as well as patients with cirrhosis or hepatitis B. PMID- 29785230 TI - Refractive indices of layers and optical simulations of Cu(In,Ga)Se2 solar cells. AB - Cu(In,Ga)Se2 based solar cells have reached efficiencies close to 23%. Further knowledge-driven improvements require accurate determination of the material properties. Here, we present refractive indices for all layers in Cu(In,Ga)Se2 solar cells with high efficiency. The optical bandgap of Cu(In,Ga)Se2 does not depend on the Cu content in the explored composition range, while the absorption coefficient value is primarily determined by the Cu content. An expression for the absorption spectrum is proposed, with Ga and Cu compositions as parameters. This set of parameters allows accurate device simulations to understand remaining absorption and carrier collection losses and develop strategies to improve performances. PMID- 29785231 TI - Advantages of evaluating gammaH2AX induction in non-clinical drug development. AB - gammaH2AX, the phosphorylated form of a histone variant H2AX at Ser 139, is already widely used as a biomarker to research the fundamental biology of DNA damage and repair and to assess the risk of environmental chemicals, pollutants, radiation, and so on. It is also beginning to be used in the early non-clinical stage of pharmaceutical drug development as an in vitro tool for screening and for mechanistic studies on genotoxicity. Here, we review the available information on gammaH2AX-based test systems that can be used to develop drugs and present our own experience of practically applying these systems during the non clinical phase of drug development. Furthermore, the potential application of gammaH2AX as a tool for in vivo non-clinical safety studies is also discussed. PMID- 29785233 TI - Therapeutic Outcome of Intralesional Immunotherapy in Cutaneous Warts Using the Mumps, Measles, and Rubella Vaccine: A Randomized, Placebo-controlled Trial. AB - Background: Various treatment modalities have been described in the literature for treating warts, but none thus far have demonstrated optimal results. Recently, the mumps, measles, and rubella (MMR) antigen has gained popularity because of its proven efficacy in the treatment of warts. Aim: The goal was to evaluate the efficacy and safety of intralesional MMR antigen in the treatment of cutaneous warts. Methods: Patients were divided into an MMR (study) group and a normal saline (control) group. Injections were administered into the single largest wart on each patient every two weeks. Follow-up was done at six weeks and 16 weeks after the last injection for any side effects and/or recurrence. Results: Out of 150 patients, 72 received the MMR injection and 50 received normal saline injections. Twenty-eight patients did not complete the study. A statistically significant (p<0.00001) difference in results was found between the two groups: 68 percent of patients in the MMR group showed complete response compared to 10 percent in the control group. Pain during injection was the most common side effect and was seen in both groups. Conclusion: MMR injection has shown significant results with almost negligible adverse effects. The MMR antigen vaccine has therapeutic potential as a treatment for warts with its demonstrated efficacy, safety profile, and cost-effectiveness. PMID- 29785232 TI - Effects of Fasudil on Patients with Pulmonary Hypertension Associated with Left Ventricular Heart Failure with Preserved Ejection Fraction: A Prospective Intervention Study. AB - Background: Pulmonary hypertension due to left ventricular heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly medical problem. The aim of the study was to evaluate the clinical efficacy of fasudil on PH-HFpEF elderly patients and to figure out the subtype of PH-HFpEF which may be the therapeutic object of fasudil. Method: 58 PH-HFpEF elderly patients were enrolled. Patients were diagnosed with passive pulmonary hypertension (PPH) or reactive pulmonary hypertension (RPH) by right heart catheterization and all receiving Rho kinase inhibitor fasudil for 2 weeks. The endpoint includes changes in SpO2, NT-pro BNP, cardiac functional classification, and echocardiography measurements after 2 weeks treatment. Results: The course of disease in the RPH group was longer than the PPH group (p < 0.05). Cardiac output was found to be worse in the RPH group than the PPH group (p < 0.01). Besides, the RPH group demonstrated a greater transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) than the PPH group (p < 0.01 for both) as well as pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (mPAP) (p < 0.01 for both), which fits the feature of RPH. After treatment of fasudil, in RPH group, PASP significantly decreased (p < 0.01) with decreased E/E' and increased E/A (p < 0.05 for both), indicating that pulmonary haemodynamics and cardiac diastolic function were ameliorated, but the measurements in the PPH group had no significant changes. NT-pro BNP and 6 MWD of both groups were improved (p < 0.05). The total effective rate of the RPH group was 74.29%, which was higher than 47.83% of the PPH group (p < 0.05). Conclusion: The Rho kinase inhibitor fasudil can improve pulmonary and left ventricular haemodynamics in patients with PH-HFpEF. The total effective rate was higher in the RPH group. Fasudil may be a promising targeted drug for the RPH in PH-HFpEF patients. This trial is registered with ChiCTR-INR-16009511. PMID- 29785234 TI - New Landmarks for the Surgical Creation of Dimples Based on Facial Form. AB - Dimleplasty is the surgical creation of dimples. The demand for dimpleplasty has increased over the past few years. Despite this increasing demand, the most widely used reference point for determining where to place a surgically created dimple, the Khoo Boo Chai (KBC) point, dates back more than 60 years. The aim of our study was to assess the facial shape of a sample of men and women, all of whom had natural dimples, to determine if characteristic patterns in dimple size, location, and shape existed according to each specific facial shapes. For our study, 1,194 people were examined for dimples and of these, 216 individuals with a group total of 336 naturally occurring dimples were included in the study. Facial form was categorized as mesoprosopic, euryprosopic, or leptoprosopic. We found that 54.8 percent of the total dimples were not positioned on the KBC point. In mesoprosopic group, out of 204 dimples, 117 were not positioned on the KBC point (87 were); in leptoprosopic group, out of 66 dimples, 30 dimples were not positioned on the KBC point (36 were); and in the euryprosopic group, out of 66 dimples, 36 were not positioned on the KBC point (30 were). Most of the dimples in the mesoprosopic group were positioned 4mm anterior to the KBC point, and in the eryprosopic group, most dimples were positioned 3mm above and behind the KBC point. Most of the dimples in the leptoprosopic group were positioned on the KBC point. We also observed differing patterns in size and shape between the groups. Understanding these differences could help surgeons achieve optimal outcomes by creating more natural looking and thus more aesthetically pleasing dimples among their patients seeking dimpleplasty. PMID- 29785235 TI - An Open-label, Observational Study Evaluating Desoximetasone Topical Spray 0.25% in Patients with Scalp Psoriasis. AB - Objective: The goal of this study was to evaluate efficacy and safety of desoximetasone spray 0.25%, a topical corticosteroid, in the management of scalp and body psoriasis. Design: This was an open-label, observational study. Participants: Twenty adults aged 18 years or older with chronic scalp psoriasis present on at least 30 percent of the scalp surface area and an Investigator Global Assessment (IGA) scale score of scalp disease of at least 2 on a scale of 0 to 4 were included in the study. Measurements: Study spray was applied twice daily for four weeks, followed by 12 weeks of twice-daily application for two consecutive days weekly. Results: At Week 4, the mean Physician Global Assessment (PGA) scale score had decreased 54.8 percent, from moderate disease to almost clear. Body surface area (BSA) had decreased by 51.2 percent, BSA * PGA had decreased by 63 percent, and scalp IGA had decreased by 64.5 percent from moderate to almost clear. Additionally, mean Psoriasis Scalp Severity Index (PSSI) score was 27.3+/-10.0 at baseline and decreased 82.4 percent to 4.8+/-5.2 and scalp surface area (SSA) was reduced by 70.7 percent at Week 4. The initial Scalp Index score was a mean of 65.7+/-15.0 at baseline and was reduced by 44.3 percent and 40.8 percent at Weeks 4 and 16, respectively. The initial response was maintained after a change to twice-weekly, twice-daily dosing, with a 48.4 percent decrease in PGA, a 17.1-percent decrease in BSA, a 31.5-percent decrease in BSA * PGA, a 51.6-percent decrease in scalp IGA, a 63.4 percent decrease in PSSI, and a 42.3-percent decrease in SSA seen at Week 16. Minimal adverse events were experienced by seven subjects. Conclusion: Desoximetasone spray 0.25% produced rapid improvements in PGA, BSA, BSA*PGA, scalp IGA, PSSI, SSA. PMID- 29785236 TI - The Efficacy of a Ceramide-based Cream in Mild-to-moderate Atopic Dermatitis. AB - Objective: The goal of this study was to determine if a therapeutic cream containing PC-104 synthetic ceramides and other ingredients could help to ameliorate signs and symptoms of mild-to-moderate atopic dermatitis and other xerotic or pruritic dermatoses. Design: In this single-site, four-week study, subjects (n=50) were instructed to apply the study product three times daily to all affected areas, including a target site for evaluation and photography at baseline, Week 2, and Week 4 visits. Setting: This study took place in the private practice of the senior author. Participants: Eligible subjects with mild to-moderate sensitive skin were included. Measurements: Evaluations included Investigator Global Assessment (IGA) scale score; subject satisfaction assessments; and noninvasive assessments of transepidermal water loss, increases in water content of the skin, and improvements in skin smoothness. Results: Use of the ceramide cream resulted in a 100-percent improvement in IGA scores and a 67-percent improvement in overall subject skin assessment scores after four weeks of use in individuals with sensitive skin conditions. Improvements were statistically significant. Statistically significant improvements were also observed in transepidermal water loss, water content of the skin, and skin smoothness. Adverse events were not observed. Conclusion: These data demonstrate that a proprietary combination of ceramide PC-104, palmitamide MEA, glycerrhetinic acid, and grape seed extract in a glycerin, dimethicone, and petrolatum vehicle was effective in reducing the signs and symptoms of mild-to moderate atopic dermatitis and other types of pruritic dermatoses (e.g., senile itch, cosmetic intolerance syndrome) in children and adults. PMID- 29785237 TI - Early Onset of Clinical Improvement with Ixekizumab in a Randomized, Open-label Study of Patients with Moderate-to-severe Plaque Psoriasis. AB - Objective: The purpose of this study was to evaluate the speed of onset of clinical response to ixekizumab (IXE) and assess the progression of visible improvement in patients with moderate-to-severe plaque psoriasis. Design: This was an interventional, randomized, open-label, Phase IIIb clinical trial. Setting: This was a single center study at the Mount Sinai School of Medicine. Participants: Twelve patients were randomized at a ratio of 1:1 to receive 80mg of ixekizumab every two (IXE Q2W) or four (IXE Q4W) weeks following a starting dose of 160mg of ixekizumab. After Week 12, all patients received 80mg IXE Q4W through Week 44. Measurements: Clinical response was measured using the Patient's Global Assessment (PatGA), the Psoriasis Area and Severity Index (PASI), the static Physician's Global Assessment (sPGA), and the Itch Numeric Rating Scale (Itch NRS). Sequential patient photographs were taken at regular intervals during the study to evaluate visible improvement in plaque psoriasis. Results: The median time to an improvement of at least 1 point or 2 points from baseline in PatGA score was 5.0 and 10.0 days for patients randomized to IXE Q2W and 6.0 and 13.5 days for patients randomized to IXE Q4W. All patients achieved at least a 50 or 75-percent improvement in PASI from baseline by Weeks 2 and 4, respectively. At least half of the patients achieved at least a 4-point improvement from baseline in Itch NRS by Day 14. Improvement in disease was visibly evident within one week of treatment in patient photographs. Conclusion: Ixekizumab results in a rapid and visible improvement in plaque psoriasis in as early as one week of treatment. PMID- 29785238 TI - Intralesional Injection of Triamcinolone Acetonide for Subcutaneous Lipoma causing Musculoskeletal and Neurologic Symptoms. AB - Objective: Benign subcutaneous lipomas can cause musculoskeletal pain and nerve impingement. We hypothesized that the potent lipolytic and atrophic effect of 40mg/mL triamcinolone acetonide would atrophy symptomatic lipomas so surgical excision could be avoided. Design: This was a cohort study. Setting: This study took place in an ultrasound injection clinic. Participants: Eight subjects with painful symptomatic lipoma were included. Measurements: Preprocedurally, the margins of the lipomas were palpated and marked with ink, then measured in centimeters (cm). Small lipomas (1-3cm) were injected with 40mg triamcinolone acetonide, while large lipomas (4-6cm) were injected with 80mg of triamcinolone acetonide. The subjects were reassessed at a four-month follow-up appointment and then again at one year and two years after the procedure. Results: Pre-injection, all eight subjects had symptoms related to impingement or pain with compression of the lipoma. At four months post-injection, none of the patients had symptoms attributable to the lipoma (p<0.001). The mean lipoma palpable dimension was 5.0+/-1.2cm prior to the injection and was 2.0+/-1.1cm at four months after the injection, with a significant mean 3.0+/-0.3cm (60%) reduction in lipoma dimensions (p<0.001). Two subjects demonstrated some mild hypopigmentation of the skin at four months post-injection. Within two years, three lipomas had symptomatically recurred, one of which was removed surgically and the two of which were reinjected. There were no infections or other serious adverse reactions that occurred. Conclusions: For individuals with painful subcutaneous lipoma, intralesional injection of 40mg/mL of triamcinolone acetonide is an effective and safe alternative to surgical excision or injection of sclerosing agents and should be considered as a reasonable therapeutic alternative in select patients. PMID- 29785239 TI - Blaschko-linear "Congenital Mixed Hemato-lymphangio-keratoma Serpiginosum" Naeviforme: A New Hybrid Entity or Various Morphological Reflections of the Two Different Vascular Abnormalities? AB - We present the case of a 15-year-old girl who presented with an unusual grouping of lesions on her upper left leg. The lesions had been present since birth. The patient had five different types of lesions: 1) transparent grouped or scattered yellowish vesicles; 2) keratotic-surfaced, grouped dark-yellowish papules; 3) bright-red grouped papules; 4) keratotic-surfaced grouped dark-red papules; and 5) patchy, punctate, and erythematous red macules. All of the lesions were intertwined along the lines of Blaschko and were in the form of irregular serpiginous plaques. Histopathological examinations of the lesions showed three main histological features, and diagnoses of the lesions were made as lymphangioma circumscriptum, lymphangiokeratoma, and verrucous hemangioma. To the best of our knowledge, such intertwined lesions have never been reported in the literature. Hence, we suggest that the name of this unique combination of lesions be "congenital nevoid mixed hemato-lymphangio-keratoma serpiginosum." PMID- 29785240 TI - This month's guideline: Visual Loss Secondary to Cosmetic Filler Injection. PMID- 29785243 TI - Oxidative Stress in Aging Brain: Nutritional and Pharmacological Interventions for Neurodegenerative Disorders. PMID- 29785241 TI - An In Vivo Zebrafish Model for Interrogating ROS-Mediated Pancreatic beta-Cell Injury, Response, and Prevention. AB - It is well known that a chronic state of elevated reactive oxygen species (ROS) in pancreatic beta-cells impairs their ability to release insulin in response to elevated plasma glucose. Moreover, at its extreme, unmitigated ROS drives regulated cell death. This dysfunctional state of ROS buildup can result both from genetic predisposition and environmental factors such as obesity and overnutrition. Importantly, excessive ROS buildup may underlie metabolic pathologies such as type 2 diabetes mellitus. The ability to monitor ROS dynamics in beta-cells in situ and to manipulate it via genetic, pharmacological, and environmental means would accelerate the development of novel therapeutics that could abate this pathology. Currently, there is a lack of models with these attributes that are available to the field. In this study, we use a zebrafish model to demonstrate that ROS can be generated in a beta-cell-specific manner using a hybrid chemical genetic approach. Using a transgenic nitroreductase expressing zebrafish line, Tg(ins:Flag-NTR)s950 , treated with the prodrug metronidazole (MTZ), we found that ROS is rapidly and explicitly generated in beta-cells. Furthermore, the level of ROS generated was proportional to the dosage of prodrug added to the system. At high doses of MTZ, caspase 3 was rapidly cleaved, beta-cells underwent regulated cell death, and macrophages were recruited to the islet to phagocytose the debris. Based on our findings, we propose a model for the mechanism of NTR/MTZ action in transgenic eukaryotic cells and demonstrate the robust utility of this system to model ROS-related disease pathology. PMID- 29785245 TI - Comment on "Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis". PMID- 29785244 TI - More than Just an Immunosuppressant: The Emerging Role of FTY720 as a Novel Inducer of ROS and Apoptosis. AB - Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression. Intriguingly, prooxidant therapies have attracted much attention due to its efficacy in cancer treatment. These strategies include diverse chemotherapeutic agents and molecular targeted drugs such as sulfasalazine which inhibits the CD44v-xCT (cystine transporter) axis. In this review, we introduce our recent discoveries using a chemical genomics approach to uncover a signaling network relevant to FTY720-mediated ROS signaling and apoptosis, thereby proposing new potential targets for combination therapy as a means to enhance the antitumor efficacy of FTY720 as a ROS generator. We extend our knowledge by summarizing various measures targeting the vulnerability of cancer cells' defense mechanisms against oxidative stress. Future directions that may lead to the best use of FTY720 and ROS-targeted strategies as a promising cancer treatment are also discussed. PMID- 29785247 TI - Being enjoyably challenged is the key to an enjoyable gaming experience: an experimental approach in a first-person shooter game. AB - Applied to video games, Csikszentmihalyi's work on flow evidences that a positive gaming experience is intrinsically self-rewarding and primarily determined by the skill/challenge balance. A multi-layered measure of enjoyment is built to take these components into account. Gamers were asked to report the concentration enjoyment they experienced during a first-person shooter game, and to better assess the gap between skill and challenge, the challenge enjoyment was also rated. Along with concentration level, concentration enjoyment is used to build a gaming experience typology that accounts for the self-rewarding component. An enjoyment-based challenge mapping is also drawn up, crossing challenge enjoyment and challenge level. The results show that this integrative enjoyment measure strengthens the causal link between challenge and gaming experience. Most importantly, the findings suggest that challenge or concentration-based enjoyment measures outweigh the standard concentration and difficulty measures as they are more likely to ensure a pleasant and positive experience (flow or relaxation) for the gamers. Indeed, regardless of the reported level of challenge, a gamer is more likely to have a positive experience when challenged at a level she perceives as pleasant. This article emphasizes the importance for game publishers of gathering enjoyment-based concentration and challenge assessments to ensure a positive gaming experience and gamers' commitment. PMID- 29785242 TI - Role of Oxidative Stress as Key Regulator of Muscle Wasting during Cachexia. AB - Skeletal muscle atrophy is a pathological condition mainly characterized by a loss of muscular mass and the contractile capacity of the skeletal muscle as a consequence of muscular weakness and decreased force generation. Cachexia is defined as a pathological condition secondary to illness characterized by the progressive loss of muscle mass with or without loss of fat mass and with concomitant diminution of muscle strength. The molecular mechanisms involved in cachexia include oxidative stress, protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction. Oxidative stress is one of the most common mechanisms of cachexia caused by different factors. It results in increased ROS levels, increased oxidation-dependent protein modification, and decreased antioxidant system functions. In this review, we will describe the importance of oxidative stress in skeletal muscles, its sources, and how it can regulate protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction involved in cachexia. PMID- 29785248 TI - Using multicriteria decision analysis during drug development to predict reimbursement decisions. AB - Background: Pharmaceutical companies design clinical development programs to generate the data that they believe will support reimbursement for the experimental compound. Objective: The objective of the study was to present a process for using multicriteria decision analysis (MCDA) by a pharmaceutical company to estimate the probability of a positive recommendation for reimbursement for a new drug given drug and environmental attributes. Methods: The MCDA process included 1) selection of decisions makers who were representative of those making reimbursement decisions in a specific country; 2) two pre-workshop questionnaires to identify the most important attributes and their relative importance for a positive recommendation for a new drug; 3) a 1 day workshop during which participants undertook three tasks: i) they agreed on a final list of decision attributes and their importance weights, ii) they developed level descriptions for these attributes and mapped each attribute level to a value function, and iii) they developed profiles for hypothetical products 'just likely to be reimbursed'; and 4) use of the data from the workshop to develop a prediction algorithm based on a logistic regression analysis. The MCDA process is illustrated using case studies for three countries, the United Kingdom, Germany, and Spain. The extent to which the prediction algorithms for each country captured the decision processes for the workshop participants in our case studies was tested using a post-meeting questionnaire that asked the participants to make recommendations for a set of hypothetical products. Results: The data collected in the case study workshops resulted in a prediction algorithm: 1) for the United Kingdom, the probability of a positive recommendation for different ranges of cost-effectiveness ratios; 2) for Spain, the probability of a positive recommendation at the national and regional levels; and 3) for Germany, the probability of a determination of clinical benefit. The results from the post-meeting questionnaire revealed a high predictive value for the algorithm developed using MCDA. Conclusions: Prediction algorithms developed using MCDA could be used by pharmaceutical companies when designing their clinical development programs to estimate the likelihood of a favourable reimbursement recommendation for different product profiles and for different positions in the treatment pathway. PMID- 29785246 TI - Modulating Metabolism to Improve Cancer-Induced Muscle Wasting. AB - Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed. PMID- 29785249 TI - Conflict of interest in Health Technology Assessment decisions: case law in France and impact on reimbursement decisions. AB - The slow reaction of French authorities to the so-called Mediator(r) saga in 2009 in France led to investigations that questioned the way conflicts of interest are reported. France implemented the Loi Bertrand ('Bertrand Law') in May 2013, known as the 'French Sunshine Act', with the aim of specifying the scope of disclosure obligations. This policy research reviewed the Loi Bertrand and reported case law from the French Council of State (COS) related to conflicts of interest in French Health technology assessment (HTA) opinion. The Loi Bertrand requires the publication of most of the agreements concluded between health-care professionals and companies and covers a vast range of health products. Commercial sales agreements of goods and services concluded between manufacturers and health-care professionals are a strong exception to this disclosure obligation. Six cases examined by the COS were analyzed, most of them related to the publication of guidelines or the removal of products from the list of reimbursed drugs and devices. These cases have been reviewed, as well as the impact of the ruling on reimbursement decisions. Four cases led to suspension or invalidation of decisions based on the Haute Autorite de Sante (HAS) recommendations due to conflicts of interest. In the two other cases, the HAS provided post hoc declarations of interest when required by the COS, and the COS considered the conflicts of interest as irrelevant for the decision. It appears that the COS based its decisions on two main criteria: the acknowledgement of negative conflicts of interest (a link with competitors) and the absence of declarations of conflicts of interest, which have to be presented when required by legal authorities irrespective of when they were completed (even posterior to the HAS opinion). However, the number of cases that have been decided against the HAS remains very limited with respect to the volume of assessments performed yearly. The strengthening of the regulation on declarations of interest might lead to more transparency but also to more cases decided by the COS. A new press investigation (in March 2015) related to alleged cases of conflict of interests led policy makers to amend the Bertrand Law in April 2015 and require the disclosure of amounts paid to health-care professionals by the industry. PMID- 29785250 TI - Pharmaceutical Market Access: current state of affairs and key challenges - results of the Market Access Launch Excellence Inventory (MALEI). AB - Objectives: To take inventory of the current state of affairs of Market Access Launch Excellence in the life sciences industry. To identify key gaps and challenges for Market Access (MA) and discuss how they can be addressed. To generate a baseline for benchmarking MA launch excellence. Methodology: An online survey was conducted with pharmaceutical executives primarily working in MA, marketing, or general management. The survey aimed to evaluate MA excellence prerequisites across the product life cycle (rated by importance and level of implementation) and to describe MA activity models in the respective companies. Composite scores were calculated from respondents' ratings and answers. Results: Implementation levels of MA excellence prerequisites generally lagged behind their perceived importance. Item importance and the respective level of implementation correlated well, which can be interpreted as proof of the validity of the questionnaire. The following areas were shown to be particularly underimplemented: 1) early integration of MA and health economic considerations in research and development decision making, 2) developing true partnerships with payers, including the development of services 'beyond the pill', and 3) consideration of human resource and talent management. The concept of importance adjusted implementation levels as a hybrid parameter was introduced and shown to be a viable tool for benchmarking purposes. More than 70% of respondents indicated that their companies will invest broadly in MA in terms of capital and headcount within the next 3 years. Conclusions: MA (launch) excellence needs to be further developed in order to close implementation gaps across the entire product life cycle. As MA is a comparatively young pharmaceutical discipline in a complex and dynamic environment, this effort will require strategic focus and dedication. The Market Access Launch Excellence Inventory benchmarking tool may help guide decision makers to prioritize their endeavors. PMID- 29785251 TI - Towards a more comprehensive approach for a total economic assessment of vaccines?: 1. The building blocks for a health economic assessment of vaccination. AB - Since we were born, we all take preventative actions to avoid unpredictable adverse conditions. Some actions are done automatically. Others require a conscious choice , either for personal or social benefit. A distinction can therefore be drawn between non-active and active prevention, and between individual and social prevention. Active prevention requires making a choice in time, effort, and cost. We call it an economic choice. Vaccines belong to the group of active and social prevention. Because a vaccination program is an economic social choice, how should it be valued, and what cost should we pay for? To date, the economic evaluations developed for treatment have been applied to vaccines. However, over 25 different characteristics differentiate vaccines from treatment. For example, the benefit of vaccination is measured at the population level not at the individual level, the main effect of prevention is societal and not an individual-based gain only, and the biggest hurdle to implement a new vaccine is the initial budget investment and not so much its estimated 'value for money'. This makes the current application of incremental cost-utility analysis difficult for vaccines for a comprehensive evaluation. New approaches may be needed to capture the full economic benefit of vaccines.. PMID- 29785252 TI - 2. How is the economic assessment of vaccines performed today? AB - This paper describes how the economic assessment of vaccines is performed today. It discusses why it may be incomplete and explores potential approaches to adjust the analysis to be more comprehensive. Besides helping protect against serious disease, vaccines also help avoid mild disease episodes that may not receive medical attention but which have important societal consequences. They also benefit unvaccinated individuals by reducing disease transmission. Wider societal benefits may extend beyond a decrease in disease incidence, as lower transmission rates reduce the risk of epidemics, which in turn reduces the pressure on healthcare providers, and may improve the quality of care for patients with unrelated diseases. Vaccines also lower the use of antibiotics leading to less pressure on anti-microbial resistance. Conventional ICUA focuses on individual health benefits, like increased survival. Therefore, this approach may not adequately capture the wider vaccination benefits. We discuss differences between treatment and vaccine prevention in the economic assessment, and how ICUA has been adapted to cope with the inconsistencies. Although such adaptations may fulfil the demand of one specific stakeholder, they may not meet the needs of other stakeholders who operate at the societal level, such as ministries other than healthcare, employers, caregivers, and insurers. PMID- 29785254 TI - Low rates of patient-reported outcome claims for orphan drugs approved by the us food and drug administration. AB - Background: Claims included in package inserts (PIs) for medicinal products approved by the US Food and Drug Administration (FDA) constitute the regulatory definition of drugs' benefits and risks. Objective: We sought to assess the usage of patient-reported outcome (PRO) claims in a comprehensive set of US FDA orphan drug approvals dated between 1/1/2012 and 31/12/2016, and characterize them. Study design: Orphan drug approval documentation was obtained from the US FDA website. Drug Package Inserts (PI) were analyzed to extract information on PRO related language. Results: Among 178 drugs that met inclusion criteria, 16 (9%) products approved for 16 orphan indications contained PRO language in the Clinical Studies section of the PI. All PRO instruments concerned disease symptoms, and two also referred to patient functioning. The most common PRO instrument was a bleed-specific rating scale for four products approved for the treatment or prevention of bleeding episodes in patients with genetic bleeding disorders. Conclusions: There is a need to implement public incentives for academic development of PRO instruments for rare conditions and for regulatory policies that mandate the collection of PRO endpoints in pivotal trials of orphan drugs. PMID- 29785253 TI - 3. How comprehensive can we be in the economic assessment of vaccines? AB - In two previous papers we argued on current vaccines economic assessment not fully comprehensive when using the incremental cost-utility analysis normally applied for treatments. Many differences exist between vaccines and drug treatments making vaccines economic evaluation more cumbersome. Four challenges overwhelmingly present in vaccines assessment are less important for treatments: requirements for population, societal perspectives, budget impact evaluation, and time focused objectives (control or elimination). Based on this, economic analysis of vaccines may need to be presented to many different stakeholders with various evaluation preferences, in addition to the current stakeholders involved for drugs treatment assessment. Then, we may need a tool making the inventory of the different vaccines health economic assessment programmes more comprehensive. The cauliflower value toolbox has been developed with that aim, and its use is illustrated here with rotavirus vaccine. Given the broader perspectives for vaccine assessment, it provides better value and cost evaluations. Cost-benefit analysis may be the preferred economic assessment method when considering substitution from treatment to active medical prevention. Other economic evaluation methods can be selected (i.e. optimisation modelling, return on investment) when project prioritisation is the main focus considered and when stakeholders would like to influence the development of the healthcare programme. PMID- 29785255 TI - Feasibility of high-intensity training in asthma. AB - Background: High-intensity interval training is an effective and popular training regime but its feasibility in untrained adults with asthma is insufficiently described. Objective: The randomized controlled trial 'EFFORT Asthma' explored the effects of behavioural interventions including high-intensity interval training on clinical outcomes in nonobese sedentary adults with asthma. In this article we present a sub analysis of data aiming to evaluate if patients' pre intervention levels of asthma control, FEV1, airway inflammation and airway hyperresponsiveness (AHR) predicted their training response to the high-intensity interval training program, measured as increase in maximal oxygen consumption (VO2max). Design: We used data from the EFFORT Asthma Study. Of the 36 patients randomized to the 8-week exercise intervention consisting of high-intensity training three times per week, 29 patients (45% females) completed the study and were included in this data analysis. Pre-intervention assessment included the asthma control questionnaire (ACQ), spirometry, fractional exhaled nitric oxide (FeNO) and AHR to mannitol. VO2 max was measured during an incremental cycle test. Results: The majority of included patients had partly or uncontrolled asthma reflected by a mean (SD) ACQ at 1.7 (0.6). Median (IQR) FeNO was 28.5 (23.8) ppb and 75% had a positive mannitol test indicating AHR. The association between patients' training response measured as increase in VO2max and pre intervention ACQ scores was not statistically significant (p = 0.49). Likewise, the association between patients' increase in VO2max and FeNO as well as AHR was not statistically significant (p = 0.80 and p = 0.58). Conclusions: Included asthma patients could adhere to the high-intensity interval protocol and improve their VO2max regardless of pre-intervention levels of asthma control, airway inflammation and AHR. PMID- 29785256 TI - Job titles classified into socioeconomic and occupational groups identify subjects with increased risk for respiratory symptoms independent of occupational exposure to vapour, gas, dust, or fumes. AB - Objectives: To evaluate the ability of three different job title classification systems to identify subjects at risk for respiratory symptoms and asthma by also taking the effect of exposure to vapours, gas, dust, and fumes (VGDF) into account. Background: Respiratory symptoms and asthma may be caused by occupational factors. There are different ways to classify occupational exposure. In this study, self-reported occupational exposure to vapours, gas, dust and fumes was used as well as job titles classifed into occupational and socioeconomic Groups according to three different systems. Design: This was a large population-based study of adults aged 30-69 years in Northern Sweden (n = 9,992, 50% women). Information on job titles, VGDF-exposure, smoking habits, asthma and respiratory symptoms was collected by a postal survey. Job titles were used for classification into socioeconomic and occupational groups based on three classification systems; Socioeconomic classification (SEI), the Nordic Occupations Classification 1983 (NYK), and the Swedish Standard Classification of Occupations 2012 (SSYK). Associations were analysed by multivariable logistic regression. Results: Occupational exposure to VGDF was a risk factor for all respiratory symptoms and asthma (odds ratios (ORs) 1.3-2.4). Productive cough was associated with the socioeconomic groups of manual workers (ORs 1.5-2.1) and non manual employees (ORs 1.6-1.9). These groups include occupations such as construction and transportation workers, service workers, nurses, teachers and administration clerks which by the SSYK classification were associated with productive cough (ORs 2.4-3.7). Recurrent wheeze was significantly associated with the SEI group manual workers (ORs 1.5-1.7). After adjustment for also VGDF, productive cough remained significantly associated with the SEI groups manual workers in service and non-manual employees, and the SSYK-occupational groups administration, service, and elementary occupations. Conclusions: In this cross sectional study, two of the three different classification systems, SSYK and SEI gave similar results and identified groups with increased risk for respiratory symptoms while NYK did not give conclusive results. Furthermore, several associations were independent of exposure to VGDF indicating that also other job related factors than VGDF are of importance. PMID- 29785257 TI - Pure erythroid leukemia in a polymyositis patient treated with azathioprine. AB - Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50-100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13. No morphological myelodysplastic changes were observed in her bone marrow cells. In this study, azathioprine accumulation was considered to be associated with the patient's leukemogenesis. PMID- 29785259 TI - The Impact of Multifaceted Osteoporosis Group Education on Patients' Decision Making regarding Treatment Options and Lifestyle Changes. AB - Introduction: Patients with chronic diseases like osteoporosis constantly have to make decisions related to their disease. Multifaceted osteoporosis group education (GE) may support patients' decision-making. This study investigated multifaceted osteoporosis GE focusing on the impact of GE on patients' decision making related to treatment options and lifestyle. Material and Methods: An interpretive description design using ethnographic methods was utilized with 14 women and three men diagnosed with osteoporosis who attended multifaceted GE. Data consisted of participant observation during GE and individual interviews. Results: Attending GE had an impact on the patients' decision-making in all educational themes. Patients decided on new ways to manage osteoporosis and made decisions regarding bone health and how to implement a lifestyle ensuring bone health. During GE, teachers and patients shared evidence-based knowledge and personal experiences and preferences, respectively, leading to a two-way exchange of information and deliberation about recommendations. Though teachers and patients explored the implications of the decisions and shared their preferences, teachers stressed that the patients ultimately had to make the decision. Teachers therefore refrained from participating in the final step of the decision-making process. Conclusion: Attending GE has an impact on the patients' decision-making as it can initiate patient reflection and support decision-making. PMID- 29785258 TI - Intra-articular biomaterials-assisted delivery to treat temporomandibular joint disorders. AB - The temporomandibular joint disorder, also known as myofascial pain syndrome, is considered one of the prevalent chronic pain diseases caused by muscle inflammation and cartilage degradation in head and neck, and thus influences even biopsychosocial conditions in a lifetime. There are several current treatment methodologies relieving inflammation and preventing degradation of the joint complex. One of the promising non-surgical treatment methods is an intra articular injection of drugs such as corticosteroids, analgesics, and anti depressants. However, the side effects of drugs due to frequent injections and over-doses, including dizziness, dry mouth, and possible drug dependency are considered limitations. Thus, the delivery of therapeutic molecules through the use of nano/microparticles is currently considered as a promising strategy primarily due to the controlled release. This review highlights the nano/microparticle systems for effective intra-articular therapeutics delivery to prevent cartilage degradation and protect subchondral bone in a temporomandibular joint. PMID- 29785260 TI - COMBATING NRAS MUTANT MELANOMA: FROM BENCH TO BEDSIDE. PMID- 29785261 TI - Aggressive fibromatosis response to tamoxifen: lack of correlation between MRI and symptomatic response. AB - Background: One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports. Methods: A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded. Results: Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms. Conclusions: No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms. PMID- 29785262 TI - Evaluation of the Relevance of DILI Predictive Hypotheses in Early Drug Development: Review of In Vitro Methodologies vs BDDCS Classification. AB - : Drug-induced liver injury (DILI) is a major safety concern; it occurs frequently; it is idiosyncratic; it cannot be adequately predicted; and a multitude of underlying mechanisms has been postulated. A number of experimental approaches to predict human DILI have been proposed utilizing in vitro screening such as inhibition of mitochondrial function, hepatobiliary transporter inhibition, reactive metabolite formation with and without covalent binding, and cellular health, but they have achieved only minimal success. Several studies have shown total administered dose alone or in combination with drug lipophilicity to be correlated with a higher risk of DILI. However, it would be best to have a predictive DILI methodology early in drug development, long before the clinical dose is known. Here we discuss the extent to which Biopharmaceutics Drug Disposition Classification System (BDDCS) defining characteristics, independent of knowing actual drug pharmacokinetics/pharmacodynamics and dose, can be used to evaluate prior published predictive proposals. Our results show that BDDCS Class 2 drugs exhibit the highest DILI severity, and that all of the short-lived published methodologies evaluated here, except when daily dose is known, do not yield markedly better predictions than BDDCS. The assertion that extensively metabolized compounds are at higher risk of developing DILI is confirmed, but can be enhanced by differentiating BDDCS Class 2 from Class 1 drugs. CONCLUSION: Our published analyses suggest that comparison of proposed DILI prediction methodologies with BDDCS classification is a useful tool to evaluate the potential reliability of newly proposed algorithms, although BDDCS classification itself is not sufficiently predictive. Almost all of the predictive DILI metrics do no better than just avoiding BDDCS Class 2 drugs, although some early data with microliver platforms enabling long-enduring metabolic competency show promising results. PMID- 29785264 TI - Delay and inequalities in the treatment of idiopathic pulmonary fibrosis: the case of two Nordic countries. AB - Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011-2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries. Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study. Data on demographics and lung function at the time of inclusion were collected. Access to antifibrotic drugs and data on disease outcomes, mortality and the proportion of patients who underwent lung transplantation, was collected during a 3-year follow up. Results: One-hundred and fifty-two patients from the Finnish and 160 patients from the Swedish IPF-cohorts were included in the study. At inclusion, Finnish patients were significantly older than the Swedish patients (74.6 years vs 72.5 years, p = 0.017). The proportion of non-smokers was significantly higher in the Finnish cohort (41.7% vs 26.9%, p = 0.007). Forced vital capacity (FVC), % of predicted (78.2 vs 71.7 for Finnish and Swedish patients, respectively, p = 0.01) and diffusion capacity for carbon monoxide (DLCO), % of predicted (53.3 vs 48.2 for Finnish and Swedish patients, respectively, p = 0.002) were significantly higher in the Finnish cohort compared to the Swedish cohort at the time of inclusion. During the 3-year follow up period, 45 (29.6%) Finnish and 111 (69.4%) Swedish patients, respectively, were initiated on treatment with an antifibrotic drug (pirfenidone or nintedanib) (p < 0.001). When comparing possible determinants of treatment, patients with higher FVC % were less likely to start antifibrotic drugs (OR 0.96, 95%CI 0.93-1.00, p < 0.024). To be resident in Sweden was the main determinant for receiving antifibrotic drugs (OR 5.48, 95%CI 2.65-11.33, p < 0.0001). No significant difference in number of deaths and lung transplantation during the follow up period was found. Conclusions: This study highlights differences concerning how IPF patients are treated in Finland and Sweden. How these differences will influence the long-term outcome of these patients is unknown. PMID- 29785263 TI - Methodologies on estimating the energy requirements for maintenance and determining the net energy contents of feed ingredients in swine: a review of recent work. AB - In the past two decades, a considerable amount of research has focused on the determination of the digestible (DE) and metabolizable energy (ME) contents of feed ingredients fed to swine. Compared with the DE and ME systems, the net energy (NE) system is assumed to be the most accurate estimate of the energy actually available to the animal. However, published data pertaining to the measured NE content of ingredients fed to growing pigs are limited. Therefore, the Feed Data Group at the Ministry of Agricultural Feed Industry Centre (MAFIC) located at China Agricultural University has evaluated the NE content of many ingredients using indirect calorimetry. The present review summarizes the NE research works conducted at MAFIC and compares these results with those from other research groups on methodological aspect. These research projects mainly focus on estimating the energy requirements for maintenance and its impact on the determination, prediction, and validation of the NE content of several ingredients fed to swine. The estimation of maintenance energy is affected by methodology, growth stage, and previous feeding level. The fasting heat production method and the curvilinear regression method were used in MAFIC to estimate the NE requirement for maintenance. The NE contents of different feedstuffs were determined using indirect calorimetry through standard experimental procedure in MAFIC. Previously generated NE equations can also be used to predict NE in situations where calorimeters are not available. Although popular, the caloric efficiency is not a generally accepted method to validate the energy content of individual feedstuffs. In the future, more accurate and dynamic NE prediction equations aiming at specific ingredients should be established, and more practical validation approaches need to be developed. PMID- 29785265 TI - A randomized controlled trial of the safety and efficacy of a topical gentamicin collagen sponge in diabetic patients with a mild foot ulcer infection. AB - Objectives: The initial phase of infection of a foot ulcer in a person with diabetes is often categorized as mild. Clinicians usually treat these infections with antimicrobial therapy, often applied topically. Some experts, however, believe that mild diabetic foot ulcer infections will usually heal with local wound care alone, without antimicrobial therapy or dressings. Methods: To evaluate the potential benefit of treatment with a topical antibiotic, we performed a single-center, investigator-blinded pilot study, randomizing (1:1) adult patients with a mild diabetic foot ulcer infection to treatment with a gentamicin-collagen sponge with local care versus local care alone. Systemic antibiotic agents were prohibited. Results: We enrolled a total of 22 patients, 11 in the gentamicin-collagen sponge arm and 11 in the control arm. Overall, at end of therapy, 20 (91%) patients were categorized as achieving clinical cure of infection, and 2 (9%) as significant improvement. At the final study visit, only 12 (56%) of all patients achieved microbiological eradication of all pathogens. There was no difference in either clinical or microbiological outcomes in those who did or did not receive the gentamicin-collagen sponge, which was very well tolerated. Conclusion: The results of this pilot trial suggest that topical antibiotic therapy with gentamicin-collagen sponge, although very well tolerated, does not appear to improve outcomes in mild diabetic foot ulcer infection. PMID- 29785266 TI - Atypical teratoid rhabdoid tumor in a 65-year-old man presenting with disseminated leptomeningeal disease: A case report and review of the literature. AB - Central nervous system atypical teratoid rhabdoid tumors are very rare aggressive tumor of childhood, primarily occurring at age of less than 3 years old. The prognosis of these tumors is very poor, with a reported median survival of 6-12 months in most cases. Treatment typically consists of aggressive chemotherapy and radiotherapy. We present the case of a 65-year-old man who presented with progressive encephalopathy and change in personality over 3 months period. The patient had further accelerated decline over 3 weeks. The diagnosis of atypical teratoid rhabdoid tumor initially remained elusive despite very extensive workup, but was eventually confirmed via open brain biopsy. To the best of our knowledge, this is the oldest reported case of atypical teratoid rhabdoid tumor in the literature. We further extend the spectrum of this rare disease. PMID- 29785267 TI - A silent massive ossification of Achilles tendon as a suspected rare late effect of surgery for club foot. AB - We report the case of a 66-year-old male patient with massive ossification of the distal portion of the Achilles tendon, as a late consequence of a surgical release for club foot conducted in his childhood. The singularity of the case report derives from its clinical features: the bone mass was of abnormal dimensions, almost substituting the entire tendon; the condition had always been asymptomatic, without deficits in range of motion, in absence of either pain or biomechanical defects with age. In fact, the condition was diagnosed just recently as a consequence of a tear. Despite an ultrasound diagnosis after the injury, only during the surgical treatment, a proper evaluation of the entity of the pathology was possible. Although the ossification of Achilles tendon is a rare clinical condition with a complex multifactorial etiology, in our case report, some of the elements in the patient's medical history could be useful for the pathogenesis and early diagnosis of the disease. The aim of this case report is to emphasize the importance both of a correct evaluation of clinical history and of an accurate diagnosis, in order to conduct a proper management of this pathology. PMID- 29785268 TI - Impact of fullerene derivative isomeric purity on the performance of inverted planar perovskite solar cells. AB - The effect of utilizing a pure cis-alpha-dimethoxy carbonyl fulleropyrrolidine C70 (DMEC70) isomer as the electron transporting material (ETM) in inverted perovskite solar cells (PSCs) was evaluated. The as-prepared C70 mono-adduct products are mixtures of regioisomers and the interest was to evaluate them independently as ETMs. Three different cis-DMEC70 isomers (alpha, beta-endo and beta-exo) (mix-DMEC70) were synthesized and purified by HPLC. It was found that PSCs based on the pure alpha-DMEC70 exhibit a substantially enhanced maximum power conversion efficiency (PCE) of 18.6% as compared to devices based on the mixed-DMEC70 isomers that yielded a PCE of 16.4%. A maximum PCE of 15.7% was observed for devices based on [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM). This work points out the importance of using pure fullerene derivative isomers as ETMs to reduce the intrinsic energy disorder, which enhances the overall device performance. PMID- 29785269 TI - Juvenile Steller sea lion (Eumetopias jubatus) utilization distributions in the Gulf of Alaska. AB - Background: A utilization distribution quantifies the temporal and spatial probability of space use for individuals or populations. These patterns in movement arise from individuals' internal state and from their response to the external environment, and thus can provide insights for assessing factors associated with the management of threatened populations. The Western Distinct Population Segment of the Steller sea lion (Eumetopias jubatus) has declined to approximately 20% of levels encountered 40 years ago. At the height of the decline, juvenile survival appeared to be depressed and currently there is evidence that juvenile mortality due to predation may be constraining recovery in some regions. Therefore, our objectives were to identify what spaces are biologically important to juvenile Steller sea lions in the Kenai Fjords and Prince William Sound regions of the Gulf of Alaska. Methods: We examined geospatial location data from juvenile sea lions tagged between 2000 and 2014 (n = 84) and derived individual and pooled-population utilization distributions (UDs) from their movements. Core areas were defined from the UDs using an individual-based approach; this quantitatively confirmed that all individuals in our sample exhibited concentrated use within their home range (95% UD). Finally, we explored if variation in UD characteristics were associated with sex, season, age, or region. Results: We found evidence that individual juvenile home ranges were region and sex-specific, with males having larger home ranges on average. Core space characteristics were also sex-specific, and exhibited seasonal patterns of reduced size, increased proximity to haulouts, and increased intensity of use in the summer, but only in the Kenai Fjords-Gulf of Alaska region. Conclusions: This study highlights the areas of biological importance during this vulnerable life history stage, and the demographic, seasonal, and spatial factors associated with variation in movement patterns for a marine mesopredator. This can be useful information for promoting species recovery, and for future efforts to understand ecological patterns such as predator-prey interactions. PMID- 29785270 TI - Distant lung metastases caused by a histologically benign phosphaturic mesenchymal tumor. AB - : Tumor-induced osteomalacia (TIO) is a rare form of hypophosphatemia usually caused by phosphaturic mesenchymal tumors (PMTs); the biologic behavior of PMTs is under investigation. Herein we present a case of TIO with a protracted course over 12 years leading to a fatal outcome. A 39-year-old man presented with weakness in 2004 and was found to have decreased serum phosphorus, phosphaturia and low levels of 1,25-dihydroxyvitamin D3. Four years later he developed a painful left calf mass. The lesion was resected, but recurred causing extreme pain and dysfunction. Radiological examination showed a large cluster of soft tissue tumors affecting all the muscle compartments of the calf and a smaller lesion inside the metaphysis of the tibia. Above-knee amputation was performed. Histological examination of all lesions showed a cellular spindle cell neoplasm with variously sized vessels, wide vessel-like spaces and scattered deposits of calcified extracellular material. The tumor infiltrated skeletal muscles, subcutaneous fat and the proximal end of the fibula. The tibial lesion had identical histology. Three years after the amputation the patient presented with cough and dyspnea. Radiological examination, followed by an open biopsy, showed that there were multiple metastatic nodules of PMTs in both lungs. Shortly after the diagnosis the patient died. This case illustrates that even benign cases of PMTs may lead to a fatal outcome and the classification of PMTs into benign and malignant should be reassessed in order to correspond to its biological behavior. Learning points: PMTs, aside from having locally aggressive behavior, may metastasize and cause deathPMTs may behave aggressively despite 'benign' histological findings Accurate diagnosis of tumor-induced osteomalacia and patient management require a multidisciplinary approach. PMID- 29785271 TI - Right ventricular dysfunction and pulmonary hypertension: a neglected presentation of thyrotoxicosis. AB - : Thyrotoxicosis is associated with cardiac dysfunction; more commonly, left ventricular dysfunction. However, in recent years, there have been more cases reported on right ventricular dysfunction, often associated with pulmonary hypertension in patients with thyrotoxicosis. Three cases of thyrotoxicosis associated with right ventricular dysfunction were presented. A total of 25 other cases of thyrotoxicosis associated with right ventricular dysfunction published from 1994 to 2017 were reviewed along with the present 3 cases. The mean age was 45 years. Most (82%) of the cases were newly diagnosed thyrotoxicosis. There was a preponderance of female gender (71%) and Graves' disease (86%) as the underlying aetiology. Common presenting features included dyspnoea, fatigue and ankle oedema. Atrial fibrillation was reported in 50% of the cases. The echocardiography for almost all cases revealed dilated right atrial and or ventricular chambers with elevated pulmonary artery pressure. The abnormal echocardiographic parameters were resolved in most cases after rendering the patients euthyroid. Right ventricular dysfunction and pulmonary hypertension are not well-recognized complications of thyrotoxicosis. They are life-threatening conditions that can be reversed with early recognition and treatment of thyrotoxicosis. Signs and symptoms of right ventricular dysfunction should be sought in all patients with newly diagnosed thyrotoxicosis, and prompt restoration of euthyroidism is warranted in affected patients before the development of overt right heart failure. Learning points: Thyrotoxicosis is associated with right ventricular dysfunction and pulmonary hypertension apart from left ventricular dysfunction described in typical thyrotoxic cardiomyopathy.Symptoms and signs of right ventricular dysfunction and pulmonary hypertension should be sought in all patients with newly diagnosed thyrotoxicosis.Thyrotoxicosis should be considered in all cases of right ventricular dysfunction or pulmonary hypertension not readily explained by other causes.Prompt restoration of euthyroidism is warranted in patients with thyrotoxicosis complicated by right ventricular dysfunction with or without pulmonary hypertension to allow timely resolution of the abnormal cardiac parameters before development of overt right heart failure. PMID- 29785272 TI - Abdominal obesity in type 1 diabetes associated with gender, cardiovascular risk factors and complications, and difficulties achieving treatment targets: a cross sectional study at a secondary care diabetes clinic. AB - Background: Abdominal obesity is linked to cardiovascular diseases in type 1 diabetes (T1D). The primary aim was to explore associations between abdominal obesity and cardiovascular complications, metabolic and inflammatory factors. The secondary aim was to explore whether achieved recommended treatment targets differed between the obese and non-obese participants. Methods: Cross sectional study of 284 T1D patients (age 18-59 years, men 56%), consecutively recruited from one secondary care specialist diabetes clinic in Sweden. Anthropometrics, blood pressure, serum-lipids and high-sensitivity C-reactive protein (hs-CRP) were collected and supplemented with data from the patients' medical records and from the Swedish National Diabetes Registry. Abdominal obesity was defined as waist circumference men/women (meters): >=1.02/>=0.88. Hs-CRP was divided into low-, moderate-, and high-risk groups for future cardiovascular events (< 1, 1 to 3, and > 3 to <=8.9 mg/l). Treatment targets were blood pressure <= 130/<= 80, total cholesterol <=4.5 mmol/l, LDL: <= 2.5 mmol/l, and HbA1c: <=5 2 mmol/mol (<= 6.9%). Different explanatory linear, logistic and ordinal regression models were elaborated for the associations, and calibrated and validated for goodness of fit with the data variables. Results: The prevalence of abdominal obesity was 49/284 (17%), men/women: 8%/29% (P < 0.001). Women (adjusted odds ratio (AOR) 6.5), cardiovascular complications (AOR 5.7), HbA1c > 70 mmol/mol (> 8.6%) (AOR 2.7), systolic blood pressure (per mm Hg) (AOR 1.05), and triglycerides (per mmol/l) (AOR 1.7), were associated with abdominal obesity. Sub analyses (n = 171), showed that abdominal obesity (AOR 5.3) and triglycerides (per mmol/l) (AOR 2.8) were associated with increasing risk levels of hs-CRP. Treatment targets were obtained for fewer patients with abdominal obesity for HbA1c (8% vs 21%, P = 0.044) and systolic blood pressure (51% vs 68%, P = 0.033). No patients with abdominal obesity reached all treatment targets compared to 8% in patients without abdominal obesity. Conclusions: Significant associations between abdominal obesity and gender, cardiovascular disease, and the cardiovascular risk factors low-grade inflammation, systolic blood pressure, high HbA1c, and triglycerides, were found in 284 T1D patients. Fewer patients with abdominal obesity reached the treatment targets for HbA1c and systolic blood pressure compared to the non obese. PMID- 29785273 TI - Gene regulation associated with sexual development and female fertility in different isolates of Trichoderma reesei. AB - Background: Trichoderma reesei is one of the most frequently used filamentous fungi in industry for production of homologous and heterologous proteins. The ability to use sexual crossing in this fungus was discovered several years ago and opens up new perspectives for industrial strain improvement and investigation of gene regulation. Results: Here we investigated the female sterile strain QM6a in comparison to the fertile isolate CBS999.97 and backcrossed derivatives of QM6a, which have regained fertility (FF1 and FF2 strains) in both mating types under conditions of sexual development. We found considerable differences in gene regulation between strains with the CBS999.97 genetic background and the QM6a background. Regulation patterns of QM6a largely clustered with the backcrossed FF1 and FF2 strains. Differential regulation between QM6a and FF1/FF2 as well as clustering of QM6a patterns with those of CBS999.97 strains was also observed. Consistent mating type dependent regulation was limited to mating type genes and those involved in pheromone response, but included also nta1 encoding a putative N-terminal amidase previously not associated with development. Comparison of female sterile QM6a with female fertile strains showed differential expression in genes encoding several transcription factors, metabolic genes and genes involved in secondary metabolism. Conclusions: Evaluation of the functions of genes specifically regulated under conditions of sexual development and of genes with highest levels of transcripts under these conditions indicated a relevance of secondary metabolism for sexual development in T. reesei. Among others, the biosynthetic genes of the recently characterized SOR cluster are in this gene group. However, these genes are not essential for sexual development, but rather have a function in protection and defence against competitors during reproduction. PMID- 29785275 TI - Infant activity and sleep behaviors in a maternal and infant home visiting project among rural, southern, African American women. AB - Background: Physical inactivity and inadequate amounts of sleep are two potential causes for excessive weight gain in infancy. Thus, parents and caregivers of infants need to be educated about decreasing infant sedentary behavior, increasing infant unrestrained floor time, as well as age specific recommended amounts of sleep for infants. The aims of this study were to determine if maternal knowledge about infant activity and sleep changed over time and to evaluate maternal compliance rates with expert recommendations for infant sleep in a two-arm, randomized, controlled, comparative impact trial. Methods: Pregnant women at least 18 years of age, less than 19 weeks pregnant, and residing in a lower Mississippi Delta county were recruited between March 2013 and December 2014. Postnatal data was collected from 54 participants between September 2013 and May 2016. McNemar's test of symmetry was used to determine if maternal knowledge changed over time, while generalized linear mixed models and Kaplan Meier survival curves were used to assess compliance with expert recommendations for infant sleep. Results: The postnatal retention rate was 85%. Maternal knowledge significantly increased for correct infant sleep position (back) and beginning tummy time by one month of age. Odds of meeting sleep duration recommendations increased by 30% for every one month increase in infant age. Only 20% of the participants were compliant with the back to sleep recommendation for the first 12 months of their infant's life; median time to noncompliance was 7.8 months. Conclusions: Although baseline knowledge concerning infant activity and sleep was high in this cohort of rural, Southern, African American mothers, compliance with recommendations was not optimal. Trial registration: The study was registered at clinicaltrials.gov (NCT01746394) on December 5, 2012. PMID- 29785274 TI - Cross-Sectional Assessment of Achievement of Therapeutic Goals in a Canadian Multidisciplinary Clinic for Patients With Advanced Chronic Kidney Disease. AB - Background: The implementation of advanced chronic kidney disease (CKD) multidisciplinary clinics has now demonstrated their effectiveness in delaying and even avoiding dialysis for patients with CKD. However, very little has been documented on the management and achievement of targets for a number of parameters in this context. Objective: Our goal was to assess our multidisciplinary clinic therapy performance in relation to the targets for hypertension, anemia, and calcium phosphate assessment. Methods: Design and setting: A cross-sectional descriptive study was conducted with a cohort including all patients followed up in our multidisciplinary clinic in July 2014. Measurements: Comorbidity, laboratory, and clinical data were collected and compared with the recommendations of scientific organizations. Results: The cohort included 128 patients, 37.5% of whom were women. Mean follow-up time was 26.6 +/- 25.1 months and mean estimated glomerular filtration rate (eGFR) was 14.0 +/- 4.7 mL/min/1.73 m2. A total of 24.2% of patients with diabetes achieved blood pressure targets of <130/80 mm Hg, while 56.5% of patients without diabetes achieved targets of <140/90 mm Hg. Hemoglobin of patients treated with erythropoiesis-stimulating agents was 100 to 110 g/L in 36.2% of the patients, below 100 for 39.7% of them, and above 110 for 24.1%, whereas 67.2% were within the acceptable limits of 95 to 115 g/L. In addition, 63.4% of patients had a serum phosphate of <1.5 mmol/L, and 90.9% of patients had total serum calcium <2.5 mmol/L. Limitations: Our study is a single center study with the majority of our patients being Caucasian. This limits the generalizability of our findings. Conclusion: The control rates of various parameters were satisfactory given the difficult clinical context, but could be optimized. We publish these data in the hope that they are helpful to others engaged in quality improvement in their own programs or more generally. PMID- 29785276 TI - Food intake attenuates the drug interaction between new quinolones and aluminum. AB - Background: Intestinal absorption of new quinolones is decreased by oral administration of polyvalent metal cations. Some clinical studies have demonstrated this drug - drug interaction is more prominent under fasted condition. However, the effect of food intake on the extent of drug - drug interaction between new quinolones and metal cations remains to be investigated quantitatively and systematically. The aim of this study was to develop an animal model that enables to evaluate the effect of food intake on the extent of drug - drug interaction in the gastrointestinal tract by chelation and to apply the model to evaluate quantitatively the effect of food intake on the drug - drug interaction between two new quinolones, ofloxacin or ciprofloxacin and sucralfate. Methods: The rats were orally administered new quinolones (5.3 mg/kg of ofloxacin or 10 mg/kg of ciprofloxacin) with or without 13.3 mg/kg of sucralfate under fasted or fed condition and plasma concentration profiles of new quinolones were monitored. To the fed group, standard breakfast used in human studies was pasted and administered at a dose of 8.8 g/kg. Results: The area under the plasma concentration - time curves (AUC0-6) of ofloxacin and ciprofloxacin under the fasted condition were significantly decreased to 28.8 and 17.1% by co-administration of sucralfate, respectively. On the contrary, sucralfate moderately decreased the AUC0-6 of ofloxacin and ciprofloxacin to 54.9 and 33.2%, respectively, under fed condition. The effects of sucralfate and food intake on the kinetics of ofloxacin in this study were well consistent with the results of previous clinical trial. Conclusions: The developed animal model quantitatively reproduced the effect of food intake on the drug - drug interaction between ofloxacin and sucralfate. The similar influences were observed for the drug - drug interaction between ciprofloxacin and sucralfate, suggesting that the extent of drug - drug interaction caused by chelation is generally attenuated by food intake. PMID- 29785277 TI - Intake and performance of lambs finished in feedlot with wet brewer's grains. AB - Background: The use of agroindustrial by-products in ruminant nutrition to be an interesting alternative in order to reduce production costs and environmental impacts arising from the inadequate destination of residues. The initial step of beer production yields a large volume of wet brewer's grains all year around, which is available at a low cost and has a high nutritional quality, and hence a big potential for animal production. Methods: Twenty-four Suffolk non-castrated male lambs, from simple parturition were kept in individual spots and allocated to four treatments constituted by four levels of substitution of sorghum silage by WBG (i.e.0; 33.5; 66.5 and 100% of substitution). It was used roughage: concentrate rate of 50:50, based on dry matter. Results: The ether extract intake increased while the acid detergent fiber intake decreased linearly (P <= 0.05). Substituion of sorghum silage by WBG did not change lambs' feed DMI, daily weight gain and feed conversion. Conclusion: The substitution of sorghum silage by WBG as roughage showed to be a viable alternative from the productive and economic point of view for finishing of feedlot lambs. PMID- 29785279 TI - Mental health recovery, goal setting and working alliance in an Australian community-managed organisation. AB - This article examines the relationships between goal setting and achievement, working alliance and recovery in an Australian mental health community-managed organisation. The study gathered data over a 14-month period after the introduction of routine outcome measures. Both goal achievement and the strength of the working alliance were shown to have a positive effect on the personal recovery of the clients in the study. Both working alliance and goal achievement are robustly supportive at whatever point a person is on in the recovery journey. The brief goals card used is a useful adjunct to other tools. PMID- 29785278 TI - Reserve-building activities attenuate treatment burden in chronic illness: The mediating role of appraisal and social support. AB - This study examines the importance of four psychosocial factors-personality, cognitive appraisal of quality of life, social support, and current reserve building-in predicting treatment burden in chronically ill patients. Chronically ill patients (n = 446) completed web-based measures. Structural equation modeling was used to investigate psychosocial factors predicting treatment burden. Reserve building activities indirectly reduced treatment burden by: (1) reducing health worries appraisals, (2) reducing financial difficulties, (3) increasing calm and peaceful appraisals, and (4) increasing perceived social support. These findings point to key behaviors that chronically ill people can use to attenuate their treatment burden. PMID- 29785280 TI - Long duration of immunity against a type 1 heterologous PRRS virus challenge in pigs immunised with a novel PRRS MLV vaccine: a randomised controlled study. AB - Background: Porcine reproductive and respiratory syndrome virus (PRRSV) is widespread in commercial pig farms worldwide, and has a significant cost to the swine industry. Herd owners need a vaccine that will confer long-lasting immunity to prevent PRRSV infection and transmission. The studies described here evaluated duration of immunity conferred by a European-derived PRRS (isolate 94,881) modified live virus (MLV) vaccine, Ingelvac PRRSFLEX(r) EU, at 20, 24, and 26 weeks post-vaccination. Primary endpoints were the assessment of gross and histological lung lesions and viral RNA load in lung tissue 10 days following heterologous PRRSV challenge. Secondary endpoints included clinical observations, average daily weight gain (ADWG) and viral RNA load in serum 10 days post challenge. Three blinded, vaccination-challenge efficacy studies were performed using separate cohorts of pigs (n = 56 per study). Pigs received either Ingelvac PRRSFLEX(r) EU (Group 1) or placebo (Groups 2 and 3). Groups 1 and 2 were subsequently challenged with heterologous European PRRSV isolate 205,817 at 20, 24 or 26 weeks post-vaccination. Results: Mean gross lung lesion scores were significantly lower in Group 1 than in Group 2 at 24 and 26 weeks (p < 0.0001), but not at 20 weeks (p = 0.299). Significantly lower mean histological lung lesion scores were observed in Group 1 versus Group 2 at 20 (p = 0.0065), 24 (p < 0.0001) and 26 weeks (p < 0.0001). Mean viral RNA load in lung tissue was significantly lower in Group 1 than in Group 2 (p < 0.0001) at 20 (p < 0.0001), 24 (p < 0.0001) and 26 weeks (p < 0.0001). Cumulative viral RNA loads in serum during days 1-10 post-challenge were significantly lower in Group 1 than in Group 2 (p < 0.0001) in all studies. A significant increase in ADWG was observed in Group 1 compared with Group 2 at 20 weeks (p = 0.0027) and 24 weeks (p = 0.0004), but not at 26 weeks (p = 0.1041). There were no significant differences in clinical signs post-challenge in any study. Conclusion: These results suggest that Ingelvac PRRSFLEX(r) EU confers long-term immunity to European heterologous PRRSV, which is maintained up to 26 weeks after vaccination, corresponding to the expected lifespan of commercial pigs. PMID- 29785281 TI - Impact of the applied simulated and integrated learning approach on nursing assistants' knowledge and confidence caring for frail seniors in nursing homes. AB - Background: Increasing importance is being placed on optimizing the role of Nursing Aides (NAs) in improving quality of care for nursing home (NH) residents. One approach to do so is to have NAs participate in assessments embedded within the Minimum Data Set (MDS). This pilot study aimed to design and evaluate the Applied Simulated and Integrated Learning Approach (ASILA) program, a novel innovative training program for NAs employed in NHs to enhance their ability to assess residents within an inter-professional framework. Methods: A mixed quantitative and qualitative repeated measures design was used to assess changes in NAs' knowledge and perception of assessments and resident clinical outcomes. Additionally, focus groups were conducted with NAs upon completion of the ASILA program. A total of 23 NAs and nurses in NHs in two Canadian provinces participated. The ASILA pilot program consisted of three selected modules; each module including an evidence-informed case-scenario, assessments, the use of appropriate MDS tools and documentation, care planing and reporting systems. ASILA was delivered over the course of two days per home. The primary outcome measure focused on the impact of ASILA on NA knowledge and confidence in assessing residents and understanding the relevance and use of elements if the MDS tools. Secondary outcomes included NAs' satisfaction with ASILA and the impact of ASILA on resident clinical outcomes. Data were collected one week prior, immediately after, and three months after the ASILA program. Results: Following ASILA, NAs reported increased knowledge test scores and confidence in assessing residents by using MDS tools, although this did not reach significance after multiple testing (p = 0.0256 and p = 0.1541 respectively). NAs reported more confidence in providing care to residents (77.8%) and felt that the care provided was more resident-centered (83.3%) than before the ASILA program. There were no significant trends in improved resident outcomes following ASILA. Conclusion: Pilot findings indicate that the ASILA program could be a successful approach to support NAs to enhance their ability to assess residents in an inter professional framework. PMID- 29785282 TI - Trabecular architecture in the sciuromorph femoral head: allometry and functional adaptation. AB - Background: Sciuromorpha (squirrels and close relatives) are diverse in terms of body size and locomotor behavior. Individual species are specialized to perform climbing, gliding or digging behavior, the latter being the result of multiple independent evolutionary acquisitions. Each lifestyle involves characteristic loading patterns acting on the bones of sciuromorphs. Trabecular bone, as part of the bone inner structure, adapts to such loading patterns. This network of thin bony struts is subject to bone modeling, and therefore reflects habitual loading throughout lifetime. The present study investigates the effect of body size and lifestyle on trabecular structure in Sciuromorpha. Methods: Based upon high resolution computed tomography scans, the femoral head 3D inner microstructure of 69 sciuromorph species was analyzed. Species were assigned to one of the following lifestyle categories: arboreal, aerial, fossorial and semifossorial. A cubic volume of interest was selected in the center of each femoral head and analyzed by extraction of various parameters that characterize trabecular architecture (degree of anisotropy, bone volume fraction, connectivity density, trabecular thickness, trabecular separation, bone surface density and main trabecular orientation). Our analysis included evaluation of the allometric signals and lifestyle-related adaptation in the trabecular parameters. Results: We show that bone surface density, bone volume fraction, and connectivity density are subject to positive allometry, and degree of anisotropy, trabecular thickness, and trabecular separation to negative allometry. The parameters connectivity density, bone surface density, trabecular thickness, and trabecular separation show functional signals which are related to locomotor behavior. Aerial species are distinguished from fossorial ones by a higher trabecular thickness, lower connectivity density and lower bone surface density. Arboreal species are distinguished from semifossorial ones by a higher trabecular separation. Conclusion: This study on sciuromorph trabeculae supplements the few non-primate studies on lifestyle-related functional adaptation of trabecular bone. We show that the architecture of the femoral head trabeculae in Sciuromorpha correlates with body mass and locomotor habits. Our findings provide a new basis for experimental research focused on functional significance of bone inner microstructure. PMID- 29785283 TI - Reporting and appraising the context, process and impact of PPI on contributors, researchers and the trial during a randomised controlled trial - the 3D study. AB - Plain English summary: Including patient and public involvement (PPI) in health research is thought to improve research but it is hard to be clear exactly how it helps. This is because PPI takes many forms, is sometimes only token and is not always reported clearly. This makes it difficult to combine the evidence so that clear conclusions can be reached about the ingredients of successful PPI and what PPI achieves. Previous research that has tried to combine the evidence has led to several guidelines for researchers to use in setting up and reporting PPI.This paper was written jointly by researchers and PPI contributors as a reflection on our experiences. The aim was to add to the evidence, by giving detail about the use of PPI in a large randomised controlled trial and the effect it had. We were guided by published PPI reporting guidelines. The effects on the trial are shown in a table of changes made because of suggestions from the PPI group. A survey was used to ask PPI contributors and researchers about their experience and effects they had noticed. Three themes were noted: impact on the trial, the effect of involvement on individual researchers and group members, and group environment. The PPI work affected the trial in many ways, including changes to documents used in the trial and advice on qualitative data collection methods and analysis. Individuals reported positive effects, including enjoying being in the group, gaining confidence, and learning how to share views. Abstract: Background: Patient and public involvement (PPI) is believed to enhance health care delivery research, and is widely required in research proposals. Detailed, standardised reporting of PPI is needed so that strategies to implement more than token PPI that achieves impact can be identified, properly evaluated and reproduced. Impact includes effects on the research, PPI contributors and researchers. Using contributor and researcher perspectives and drawing on published guidelines for reporting PPI, we aimed to reflect on our experience and contribute evidence relevant to two important questions: 'What difference does PPI make?' and 'What's the best way to do it?' Methods: Fourteen people living with multiple long-term conditions (multimorbidity) were PPI contributors to a randomised controlled trial to improve care for people with multimorbidity. Meetings took place approximately four times a year throughout the trial, beginning at grant application stage. Meeting notes were recorded and a log of PPI involvement was kept. At the end of the trial, seven PPI contributors and four researchers completed free-text questionnaires about their experience of PPI involvement and their perception of PPI impact. The responses were analysed thematically by two PPI contributors and one researcher. The PPI group proposed writing this report, which was co-authored by three PPI contributors and two researchers. Results: Meeting attendance averaged nine PPI contributors and three to four researchers. The involvement log and meeting notes recorded a wide range of activities and impact including changes to participant documentation, advice on qualitative data collection, contribution to data analysis and dissemination advice. Three themes were identified from the questionnaires: impact on the study, including keeping the research grounded in patient experience; impact on individuals, including learning from group diversity and feeling valued; and an environment that facilitated participation. The size of the group influenced impact. Researchers and PPI contributors described a rewarding interaction that benefitted them and the research. Conclusions: PPI was wide-ranging and had impact on the trial, contributors and researchers. The group environment facilitated involvement. Feedback and group interactions benefitted individuals. The insights gained from this study will postitively influence the researchers' and contributors' future involvement with PPI. PMID- 29785284 TI - Vinorelbine-induced regression of a choroidal metastasis from primary breast carcinoma. AB - Background: Various therapeutic options exist to treat choroidal metastatic lesions. However, they are all associated with potential long-term adverse effects. This case report discusses a case of choroidal metastasis from primary breast carcinoma that regressed after single-agent chemotherapy. Case presentation: We report a case of choroidal metastasis from estrogen receptor (ER) positive breast carcinoma that became resistant to endocrine therapy. The primary malignancy was treated with surgical resection and adjuvant chemoradiation, followed by hormone therapy with various agents in combination with kinase inhibitors for ER resistance. The choroidal metastatic lesion regressed after the initiation of vinorelbine. Vinorelbine is a cytotoxic vinca alkaloid with tolerable systemic adverse effects. Conclusions: This case report highlights the possible role of vinorelbine as a single chemotherapeutic agent for the conservative therapy of uveal metastasis from advanced breast carcinoma, irrespective of responsiveness to hormone therapy. PMID- 29785285 TI - A conference at the onset of a new era. PMID- 29785286 TI - Anatomical variations and pitfalls to know during thoracoscopic segmentectomies. AB - The rate of sublobar resection (SLR) for early-stage non-small cell lung carcinoma (NSCLC) is increasing, mainly because of a growing rate of early-stage lung carcinomas and ground-glass opacities. More and more SLRs are now performed by a thoracoscopic, a video-assisted or a robotically-assisted approach. Although surgeons are performing pulmonary segmentectomies for years, they need a better understanding of anatomy when using a closed chest approach, because vision is more limited and they cannot stretch and expose the parenchyma and broncho vascular elements. In this article, we will describe most of the significant anatomical variations we have encountered during a consecutive series of 390 full thoracoscopic segmentectomies, either at surgery or preoperatively by studying the 3-dimensional (3D) modelisation. PMID- 29785288 TI - T1a lung carcinoma: the place of segmentectomy in the treatment array. AB - Contemporary management of early stage non-small cell lung cancer (NSCLC) is evolving and can be attributed to a change in size and histology of lung cancer, advancements in imaging modalities, instrumentation and surgical techniques. The emergence of segmentectomy has further challenged the existing treatment landscape, with promising results. Despite limited widespread adoption, video assisted thoracoscopic surgery (VATS) segmentectomy is a safe option in the treatment of patients with small stage I lung cancers, with excellent oncologic results and improved morbidity relative to open techniques. In this paper, we critically examine the utility of segmentectomy, and the emerging role of VATS, including technical tips and tricks, in the management of T1a lung carcinoma. PMID- 29785287 TI - Lymph node dissection during sublobar resection: why, when and how? AB - Appropriate lymph node (LN) assessment is a hallmark of surgical quality of curative intent operations for non-small cell lung cancer (NSCLC). Even in the era of extensive pre-treatment work-up including routine PET-scanning and brain imaging, and selective invasive LN evaluation, unexpected LN metastases are found at surgery in more than 10% of patients with a cT1aN0 tumor. Systematic lymphadenectomy minimizes the risk of leaving tumor-LN behind and thus the risk of an incomplete resection, and provides the most truthful pTNM, which is decisive in directing adjuvant chemotherapy. Removal of interlobar, hilar, and mediastinal LNs is necessary during sublobar resection, as it is during lobectomy. In addition, segmental LNs should be dissected at both the resected and nonresected lobar segments, because the lymphatic flow from the resected segment can go directly to the neighboring segmental LNs to join the lymphatic network at the roots of the lobar bronchi, especially for tumors in anteriorly located segments. Finally, several anatomical studies described direct lymphatic vessels from the lower lobes into the upper lobar bronchi LN rendering also advisable clearance of the upper lobar LN in case of lower lobe NSCLC. Given that intralobar LN dissection is impossible within the remaining lobe after wedge resection, omission of segmental and intralobar LN retrieval may also explain the high incidence of loco-regional recurrence observed after wedge resection. Thus, segmentectomy should be preferred to wedge resection as the recommended type of sublobar resection. PMID- 29785289 TI - What is the role of wedge resection for T1a lung cancer? AB - Since 1995, lobar resection became the standard of care for medically fit patients with early stage lung cancer. This was based on the results of a single randomized trial comparing lobectomy and sublobar resection (SLR) in stage I lung cancer conducted by the lung cancer study group between 1982 and 1988. The conclusions of the study included a statistically significant tripling in loco regional recurrence (LR) after limited resection but no difference between the two arms of the trial in systemic recurrence. Although both overall survival and cancer specific survival favored lobectomy, neither achieved statistical significance. Regardless, this landmark trial established lobectomy as the preferred oncological resection for early stage lung cancer. The practice of thoracic surgery has evolved significantly since the study period of the Lung Cancer Study Group, and this has led some surgeons to question its relevance to contemporary practice. The increased detection of smaller more precisely staged tumors combined with the rising segment of the population that is elderly with limited cardiopulmonary reserve has renewed interest in sub-lobar resection including wedge resection as either a definitive therapeutic strategy or as a compromise approach in patients with poor performance status. The interest in wedge resections is also to some extent further fueled by the emergence and increased utilization of competing technologies of local control such as stereotactic radiation or percutaneous and trans-bronchial ablative techniques. Although the results of the LCSG still cast a long shadow over the soundness of wedge resection as a cancer operation, much literature has been published in the subsequent years on this topic. We present in this review an overview of the conflicting data and offer our perspective on the role of wedge resection in early stage lung cancer. PMID- 29785290 TI - Endobronchial treatment of peripheral tumors: ongoing development and perspectives. AB - The expanded possibilities to explore the lung deeper with new tools such as electromagnetic navigation bronchoscopy (ENB) or radial probe endobronchial ultrasonography (radial EBUS), combined with miniaturization of traditional local therapies such as radiofrequency ablation (RFA), radiotherapy, cryotherapy or photodynamic therapy, let the bronchoscopists hope for new ways of endoscopic treatments. This challenge could change the practice in the upcoming decades but raise some physical and technical issues. Safety and efficacy need to be solidly established to face the serious concurrence of stereotactic radiotherapy (SBRT) or percutaneous RFA. Here we describe ongoing development and perspectives for endobronchial treatment of peripheral lung tumors. PMID- 29785291 TI - Using novel technology to augment complex video-assisted thoracoscopic single basilar segmentectomy. AB - There are many novel technologies that enable complex segmentectomy to be performed. As lung cancer screening becomes more prevalent, patients are increasingly diagnosed with early stage lung cancer, multifocal disease, and second primary tumors. This shift to an earlier clinical presentation combined with advances in technology and an emphasis on minimally invasive techniques have led to the current developments we are now seeing with anatomic segmentectomy. In this paper, we describe the operative technique of an indocyanine green (ICG) guided video-assisted thoracoscopic surgery (VATS) single basilar segmental resection, augmented with methylene blue dye marker localization via SuperDimension electromagnetic navigational bronchoscopy. The CT scans of the posterior basal segment tumor are enhanced with three-dimensional (3D) modeling. A description of the approach is detailed with a video, intraoperative photographs, and illustrations. Successful removal of the S10 segment with novel techniques permitted the patient to have five percent of the lung removed (segmentectomy) instead of 25% (right lower lobectomy). In the setting of multifocal disease, future treatment options for the tumors in other locations of the lung are enhanced. Novel lung imaging techniques along with careful intraoperative identification of appropriate segmental anatomy allow patients to be offered an optimal basilar parenchymal-sparing segmentectomy. PMID- 29785292 TI - Thoracoscopic stapler-based "bidirectional" segmentectomy for posterior basal segment (S10) and its variants. AB - Thoracoscopic segmentectomy for the posterior basal segment (S10) and its variant (e.g., S9+10 and S10b+c combined subsegmentectomy) is one of the most challenging anatomical segmentectomies. Stapler-based segmentectomy is attractive to simplify the operation and to prevent post-operative air leakage. However, this approach makes thoracoscopic S10 segmentectomy even more tricky. The challenges are caused mostly from the following three reasons: first, similar to other basal segments, "three-dimensional" stapling is needed to fold a cuboidal segment; second, the belonging pulmonary artery is not directly facing the interlobar fissure or the hilum, making identification of target artery difficult; third, the anatomy of S10 and adjacent segments such as superior (S6) and medial basal (S7) is variable. To overcome these challenges, this article summarizes the "bidirectional approach" that allows for solid confirmation of anatomy while avoiding separation of S6 and the basal segment. To assist this approach under limited thoracoscopic view, we also show stapling techniques to fold the cuboidal segment with the aid of "standing stiches". Attention should also be paid to the anatomy of adjacent segments particularly that of S7, which tends to be congested after stapling. The use of virtual-assisted lung mapping (VAL-MAP) is also recommended to demark resection lines because it flexibly allows for complex procedures such as combined subsegmentectomy such as S10b+c, extended segmentectomy such as S10+S9b, and non-anatomically extended segmentectomy. PMID- 29785293 TI - Planning and marking for thoracoscopic anatomical segmentectomies. AB - Although sublobar resection (SLR) for treating non-small cell lung carcinoma (NSCLC) is still controversial, thoracoscopic segmentectomy is rising. Performing it by closed chest surgery is complex as it means confirming the location of the lesion, identifying vascular and bronchial structures, preserving venous drainage of adjacent segments, severing the intersegmental plane and ensuring an oncological safety margin with no manual palpation and different landmarks. Accurate planning is mandatory. We discuss in this article the interest of 3D reconstruction and mapping technics to enhance safety and reliability of these procedures. PMID- 29785294 TI - Development of a precision multimodal surgical navigation system for lung robotic segmentectomy. AB - Minimally invasive sublobar anatomical resection is becoming more and more popular to manage early lung lesions. Robotic-assisted thoracic surgery (RATS) is unique in comparison with other minimally invasive techniques. Indeed, RATS is able to better integrate multiple streams of information including advanced imaging techniques, in an immersive experience at the level of the robotic console. Our aim was to describe three-dimensional (3D) imaging throughout the surgical procedure from preoperative planning to intraoperative assistance and complementary investigations such as radial endobronchial ultrasound (R-EBUS) and virtual bronchoscopy for pleural dye marking. All cases were operated using the DaVinci SystemTM. Modelisation was provided by Visible PatientTM (Strasbourg, France). Image integration in the operative field was achieved using the Tile Pro multi display input of the DaVinci console. Our experience was based on 114 robotic segmentectomies performed between January 2012 and October 2017. The clinical value of 3D imaging integration was evaluated in 2014 in a pilot study. Progressively, we have reached the conclusion that the use of such an anatomic model improves the safety and reliability of procedures. The multimodal system including 3D imaging has been used in more than 40 patients so far and demonstrated a perfect operative anatomic accuracy. Currently, we are developing an original virtual reality experience by exploring 3D imaging models at the robotic console level. The act of operating is being transformed and the surgeon now oversees a complex system that improves decision making. PMID- 29785295 TI - Uniportal video-assisted thoracoscopic segmentectomy. AB - Uniportal video-assisted thoracoscopic surgery (VATS) segmentectomy is a technically more complex procedure than uniportal VATS lobectomy, since a detailed comprehension of the segmental anatomy is required. Anatomic sublobar resection can achieve outcomes equivalent to lobectomy in selected patients with stage IA non-small cell lung carcinoma (NSCLC). In this paper we describe our clinical experiences and introduce the technical details of uniportal VATS segmentectomy, including expertise advice ("tips and tricks") in patient selection, positioning and incisions and technical highlights of the most common types of segmentectomies. Uniportal VATS segmentectomy is a demanding technique, safe and feasible in selected patients with good results in the literature that seems to be an acceptable alternative to conventional VATS or open thoracotomy when the surgeon completed the training period and learning curve. PMID- 29785296 TI - Division of the intersegmental plane using electrocautery for segmentectomy in clinical stage I non-small cell lung cancer. AB - Background: Division of intersegmental planes is one of the important practical issues for segmentectomy to obtain feasible outcomes without relapse for clinical stage I non-small cell lung cancer. Almost all surgeons perform this procedure using a stapler. However, division of intersegmental planes for segmentectomy can also be performed by electrocautery. In this article, we demonstrate the merits and drawbacks of division of the intersegmental plane by electrocautery for segmentectomy. Methods: Of those 125 patients who underwent segmentectomy with clinical stage I primary lung cancer, we compared cautery cases (n=50) with stapler cases (n=75). The cautery group included 29 cases (58.0%) with partial use of a staple at the end of division. Results: Operative time was significantly longer in cautery cases (281+/-72 min) than stapler in cases (235+/-86 min; P=0.003). No difference in the duration of chest tube placement was evident between cautery (3.0+/-3.0 days) and stapler groups (2.8+/-1.7 days; P=0.613). However, delayed air leakage occurred significantly more frequently in cautery cases (14.0%) than in stapler cases (4.0%; P=0.048). Five-year overall survival (OS) in clinical stage I was 94.7% in cautery cases and 80.5% in stapler cases (log-rank P=0.047). Five-year disease-free survival (DFS) was 80.0% and 71.3%, respectively (log-rank P=0.075). Conclusions: The merits of cautery division include the ability to achieve meticulous division of the intersegmental plane and good preservation of the shape of residual segments. Conversely, the drawbacks include prolonged air leakage. Pleural suture or closure of residual segments may be useful to prevent delayed air leakage. PMID- 29785297 TI - Determination of the intersegmental plane using the slip-knot method. AB - Background: Visualization of intersegmental planes in the lung is desirable for precise anatomical lung segmentectomy. We developed the slip-knot method for creating inflation-deflation lines. This study aimed to assess relevant data for thoracoscopic segmentectomy performed using this method. Methods: In the slip knot method, the objective segmental bronchus is looped with a monofilament thread. One end of the thread is then pulled during temporary bilateral ventilation, causing the knot to slip toward the bronchus. Thereafter, bronchial ligation is tightened to block the outflow of segmental air, ensuring that the segment remains expanded while the other reserved segments collapse on resumption of unilateral ventilation. Data from 221 patients who underwent thoracoscopic pulmonary segmentectomy between 2010 and 2016 were analyzed. Results: A total of 147 patients (67%) were indicated for the slip-knot method, and 74 cases (33%) were non-adaptive cases. Ninety six percent of 147 cases were well adapted to the slip-knot method, which allowed us to obtain good inflation-deflation line images to determine the intersegmental plane. The mean operative time was 171+/-51 min (range, 71-367 min). The mean duration of chest tube insertion was 1.5+/-1.2 days (range, 1-7 days). Three cases (2.0%) had prolonged air-leakage and one (0.7%) case had readmission for late air-leakage. Conclusions: Our method enables determination of anatomical intersegmental planes using only one monofilament thread, thus facilitating thoracoscopic pulmonary anatomical segmentectomy. PMID- 29785298 TI - Impact of near-infrared angiography on the quality of anatomical resection during video-assisted thoracic surgery segmentectomy. AB - Background: The aim of the present study was to assess the impact of near infrared angiography in guiding intraoperatively sublobar anatomical resection by video-assisted thoracic surgery (VATS). Methods: We retrospectively analyzed data from 67 patients who underwent segmentectomy by VATS from November 2014 to November 2017 at the University Hospitals of Geneva, Switzerland. The need to modify arterial or parenchymal resection based on intraoperative near-infrared imaging was considered the primary study outcome. Results: A total of 67 patients (28 men, 39 women, mean age 66+/-10 years) underwent anatomical pulmonary segmentectomy by VATS. Histological analysis revealed a primary lung tumor in 59 patients. The mean +/- standard deviation (SD) operation time was 154+/-51 minutes. Identification of the intersegmental plane (ISP) with near-infrared angiography was achieved in 88% of patients and led to modification of the resection during segmentectomy in 7 patients (10%), avoiding inappropriate resection; 2 patients had distant tumor recurrences (3%). Conclusions: Near infrared angiography during VATS segmentectomy is effective for identifying ISPs, with respect to the oncological margins, as well as for correcting the anatomical resection. PMID- 29785299 TI - Thoracoscopic segmentectomy: hybrid approach for clinical stage I non-small cell lung cancer. AB - Background: Recently, minimally invasive surgical approaches have been developed, typified by video-assisted thoracic surgery (VATS). A meticulous surgical procedure to prevent local recurrence is required during segmentectomy for clinical stage I non-small-cell primary lung cancer. In this article, we demonstrated the validity of hybrid VATS segmentectomy. Methods: Of these 125 patients, 62 (49.6%) underwent intensively radical segmentectomy (RS). The remaining 63 (50.4%) patients underwent palliative segmentectomy (PS). We used two 2-cm ports and performed a muscle-sparing mini-thoracotomy in which a partially open metal retractor allowed direct, thoracoscopic visualization as hybrid VATS segmentectomy in 63.2% of our cases. Results: The consolidation/tumor ratio obtained with thin-sliced computed tomography was significantly lower in RS cases than in PS cases (P=0.001). The proportion of pathological stage IA cases was significantly higher in RS cases (95.2%) than in PS cases (66.7%; P<0.01). Five-year overall survival (OS) for clinical stage I was 100.0% in RS cases and 73.5% in PS cases (log-rank P<0.001). Five-year disease-free survival (DFS) was 95.5% and 55.7%, respectively (log-rank P<0.001). Conclusions: During segmentectomy, the most critical consideration is establishment of sufficient surgical margins around the cancer. Our hybrid approach that includes meticulous surgical manipulations may produce sufficient surgical margins. PMID- 29785300 TI - Corneal Stability following Hyperopic LASIK with Advanced Laser Ablation Profiles Analyzed by a Light Propagation Study. AB - Purpose: To assess anterior corneal surface stability 12 months following hyperopic LASIK correction with a light propagation algorithm. Setting: Vissum Instituto Oftalmologico de Alicante, Universidad Miguel Hernandez, Alicante, Spain. Methods: This retrospective consecutive observational study includes 37 eyes of 37 patients treated with 6th-generation excimer laser platform (Schwind Amaris). Hyperopic LASIK was performed in all of them by the same surgeon (JLA) and completed 12-month follow-up. Corneal topography was analyzed with a light propagation algorithm, to assess the stability of the corneal outcomes along one year of follow-up. Results: Between three and twelve months postoperatively, an objective corneal power (OCP) regression of 0.39 D and 0.41 D was found for 6 mm and 9 mm central corneal zone, respectively. Subjective outcomes at the end of the follow-up period were as follows: 65% of eyes had spherical equivalent within +/-0.50 D. 70% of eyes had an uncorrected distance visual acuity 20/20 or better. 86% of eyes had the same or better corrected distance visual acuity. In terms of stability, 0.14 D of regression was found. No statistically significant differences were found for all the study parameters evaluated at different postoperative moments over the 12-month period. Conclusions: Light propagation analysis confirms corneal surface stability following modern hyperopic LASIK with a 6th-generation excimer laser technology over a 12-month period. PMID- 29785301 TI - Impact of Baseline Central Retinal Thickness on Outcomes in the VIVID-DME and VISTA-DME Studies. AB - Purpose: To report the impact of baseline central retinal thickness (CRT) on outcomes in patients with diabetic macular edema (DME) in VIVID-DME and VISTA DME. Methods: Post hoc analyses of two randomized controlled trials in which 862 DME patients were randomized 1 : 1 : 1 to treatment with intravitreal aflibercept 2.0 mg every 4 weeks (2q4), intravitreal aflibercept 2.0 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline and as needed. We compared visual and anatomical outcomes in subgroups of patients with baseline CRT < 400 MUm and >=400 MUm. Results: At weeks 52 and 100, outcomes with intravitreal aflibercept 2q4 and 2q8 were superior to those in laser control-treated patients regardless of baseline CRT. When looked at in a binary fashion, the treatment effect of intravitreal aflibercept versus laser was not significantly better in the >=400 MUm than the <400 MUm group; when looked at as a continuous variable, baseline CRT seemed to have an impact on the treatment effect of intravitreal aflibercept versus laser. Conclusions: Post hoc analyses of VIVID-DME and VISTA-DME demonstrated the benefits of intravitreal aflibercept treatment in DME patients with baseline CRT < 400 MUm and >=400 MUm. This trial is registered with NCT01331681 and NCT01363440. PMID- 29785302 TI - Comparisons of Visual and Surgical Outcomes after Reuse or Replacement of Dislocated in-the-Bag Intraocular Lens. AB - Purpose: To compare the visual and surgical outcomes after a reuse or a replacement of a dislocated in-the-bag intraocular lens (IOL). Methods: This was a retrospective, nonrandomized case series at a single ophthalmological institution. Cases with an in-the-bag dislocation of an IOL were treated by pars plana vitrectomy and the reuse or the replacement of the IOL. The lens was held by intrascleral fixation of the haptics of the IOL under both conditions. The same dislocated IOL was reused in 6 eyes (group A) or it was replaced with another IOL in the other 9 eyes (group B). The pre- and postoperative parameters analyzed included the visual acuity, refractive error, corneal endothelial cell density, and intraocular pressure (IOP). Results: There was no significant difference between the two groups in the postoperative visual acuity (P = 0.388), refractive error (P = 0.955), IOP (P = 0.529), and endothelial cell loss (P = 0.940). A breakage or a tilting of the IOL was observed and required replacement in three eyes in the reuse group (P = 0.044). Conclusions: Half of the cases with reused in-the-bag dislocated IOL had a breakage or a tilting of the IOL. The replacement of the in-the-bag dislocated IOL is better than the reuse of the IOL with intrascleral haptics fixation. PMID- 29785303 TI - Ocular Manifestations of Biopsy-Proven Pulmonary Sarcoidosis in Korea. AB - Purpose: To investigate the clinical features and ocular manifestations of biopsy proven pulmonary sarcoidosis in Korea. Methods: 55 patients diagnosed with pulmonary sarcoidosis by bronchoscopic or excisional biopsy were included. By retrospective clinical chart review, we investigated features of uveitis, ocular and systemic treatments, visual acuity, angiotensin-converting enzyme level, chest radiography, and pulmonary function tests. Clinical features were analyzed by presence of uveitis, site of biopsy, and first manifested sign of sarcoidosis. Results: The group with uveitis (n = 39) presented with higher systemic (71.8%) and immunosuppressive treatment rates (35.9%) than the group without uveitis (31.3%, 0%, resp.) (P = 0.007, P = 0.005, resp.). There were no significant differences in clinical features, including systemic treatment rate, by type of biopsy. Of 39 patients with uveitis, the group with ocular manifestation as a first sign of sarcoidosis showed higher systemic and immunosuppressive treatment rates (88.9%, 55.6%) compared to the group with pulmonary manifestation as a first sign (57.1%, 19.0%) (P = 0.037, P = 0.018, resp.). Conclusions: In patients with biopsy-proven pulmonary sarcoidosis, the presence of ocular involvement and uveitis as a first sign could be significant factors associated with higher systemic treatment rate, especially with immunosuppressive agents. Biopsy site determined by location and size had no influence on clinical features. PMID- 29785304 TI - Application of 25 MHz B-Scan Ultrasonography to Determine the Integrity of the Posterior Capsule in Posterior Polar Cataract. AB - Purpose: To report the application of 25 MHz B-scan ultrasonography (MHzB) to determine the integrity of the posterior capsule (PC) in posterior polar cataract (PPC). Methods: Patients with whom PPC was clinically diagnosed using slit lamp microscopy who underwent 25 MHzB before phacoemulsification were retrospectively reviewed. The status of the PC was determined by 25 MHzB before phacoemulsification and confirmed during cataract surgery. Results: In total, 21 eyes in 14 clinically diagnosed PPC patients were enrolled in this study. Out of 25 MHzB images, 19 PCs were found to be intact, while 2 showed dehiscence before cataract surgery. During phacoemulsification, 17 PCs were observed to be intact, while 4 PCs showed posterior capsule rupture (PCR). These 4 PCR cases included the above 2 eyes, in which preexisting dehiscence was detected by 25 MHzB. The other 2 PCR cases showed high reflectivity between high echoes in posterior opacities and the PC, indicating synechia between the PPC and PC. Conclusion: This is the first report to show that 25 MHzB can be used to clearly visualize the status of the PC in PPC. These results, in turn, could be used to select the appropriate treatment and to thereby avoid further complications during PPC surgery. PMID- 29785305 TI - Comparable Enhanced Prothrombogenesis in Simple Central Obesity and Metabolic Syndrome. AB - Objective: There is limited data comparing prothrombogenic or fibrinolysis biomarkers (tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)) simultaneously in subjects with Metabolic Syndrome (MS), simple central obesity without MS (COB) and normal controls (NC). We investigated the concentrations of fibrinolysis biomarkers in subjects with MS, COB and NC. Methods: A cross-sectional study involving 503 drug naive subjects (163 males, aged 30-65 years old (mean age +/- SD = 47.4 +/- 8.3 years)) divided into MS, COB and NC groups. COB was defined as central obesity (waist circumference (WC) males >=90 cm, females >=80 cm) in the absence of MS according to the International Diabetes Federation 2006. Fasting blood levels of tPA and PAI-1were analyzed. Results: MS and COB had significantly higher concentration of all biomarkers compared to NC. The MS group had significantly higher concentration of tPA and PAI-1 compared to COB. WC and HDL-c had significant correlation with all biomarkers (tPA p < 0.001, PAI-1 p < 0.001). Fasting plasma glucose and diastolic blood pressure were independent predictors after correcting for confounding factors. Conclusion: Central obesity with or without MS both demonstrated enhanced prothrombogenesis. This suggests that simple obesity possibly increases the risk of coronary artery disease in part, via increased susceptibility to thrombogenesis. PMID- 29785306 TI - Overweight and Undernutrition in the Cases of School-Going Adolescents in Wolaita Sodo Town, Southern Ethiopia: Cross-Sectional Study. AB - Background: This study aimed to assess the prevalence of malnutrition and associated factors among school adolescents in Wolaita Sodo town, Southern Ethiopia. Methods: A school-based cross-sectional study was conducted from May 18 June 10, 2015. A multistage sampling was used to select a random sample of 690 adolescents from selected schools. Data on sociodemographic information were collected by using an interviewer-administered questionnaire, and anthropometric measurements were made by using a digital Seca scale and height measuring board by trained data collectors. Data were entered into Epi-Data version 3.1 software and exported to SPSS version 20. World Health Organization (WHO) Anthro-plus software was used to analyze anthropometric data. Both binary and multinomial logistic regression analyses were done to identify factors associated with the malnutrition of adolescents. Result: The overall prevalence of thinness, stunting, and overweight/obesity among school adolescents was 4.7% (95% CI: 3% 6.4%); 5.2% (95% CI: 3.4%-7%); and 5.0% (95% CI: 3.4%-6.7%), respectively. Being male (AOR = 4.07; 95% CI: 2.35-7.02), learning at a government school (AOR = 0.37; 95% CI: 0.20-0.65), mothers with no formal education (AOR = 4.03; 95% CI: 1.82-8.92), owning no cattle (AOR = 4.92; 95% CI: 2.08-11.64), skipping meals (AOR = 1.70; 95% CI: 1.05-2.74), and illness in 2 weeks prior to survey (AOR = 2.67; 95% CI: 1.49-4.78) were significantly associated with thinness. However, males, students who had their house, and no cattle were more likely to develop overweight/obesity. Maternal education of secondary school (AOR = 0.214; 95% CI: 0.054-0.846) was significantly associated with the stunting. Conclusion: The study showed the coexistence of undernutrition and overnutrition among school adolescents in the study area. There needs to implement evidence-based school nutrition education and health policies and programs to improve nutritional status of adolescents and timely taking action to limit obesity-related health problems. PMID- 29785307 TI - A Review of Percutaneous Transluminal Angioplasty in Hemodialysis Fistula. AB - The number of patients in dialysis increases every year. In this review, we will evaluate the role of percutaneous transluminal angioplasty (PTA) according to patency of arteriovenous fistula and grafts. The main indication of PTauAlpha is stenosis > 50% or obstruction of the vascular lumen of an arteriovenous fistula and graft. It is usually performed under local anesthesia. The infection rate is as low as the number of complications. Fistula can be used in dialysis in the same day without the need for a central venous catheter. Primary patency is >50% in the first year while primary assisted patency is 80-90% in the same time period. Repeated PTA is as durable as the primary PTA. An early PTA carries a risk of new interventions. Cutting balloon can be used as a second-line method. Stents and covered stents are kept for the management of complications and central outflow venous stenosis. PTA is the treatment of choice for stenosis or obstruction of dialysis fistulas. Repeated PTA may be needed for better patency. Drug eluting balloon may become the future in PTA of dialysis fistula, but more trials are needed. PMID- 29785308 TI - The Correlation of Dyslipidemia with the Extent of Coronary Artery Disease in the Multiethnic Study of Atherosclerosis. AB - Background: The extent of coronary artery calcium (CAC) improves cardiovascular disease (CVD) risk prediction. The association between common dyslipidemias (combined hyperlipidemia, simple hypercholesterolemia, metabolic Syndrome (MetS), isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipidemia and the risk of multivessel CAC is underinvestigated. Objectives: To determine whether there is an association between common dyslipidemias compared with normolipidemia, and the extent of coronary artery involvement among MESA participants who were free of clinical cardiovascular disease at baseline. Methods: In a cross-sectional analysis, 4,917 MESA participants were classified into six groups defined by specific LDL-c, HDL-c, or triglyceride cutoff points. Multivessel CAC was defined as involvement of at least 2 coronary arteries. Multivariate Poisson regression analysis evaluated the association of each group with multivessel CAC after adjusting for CVD risk factors. Results: Unadjusted analysis showed that all groups except hypertriglyceridemia had statistically significant prevalence ratios of having multivessel CAC as compared to the normolipidemia group. The same groups maintained statistical significance prevalence ratios with multivariate analysis adjusting for other risk factors including Agatston CAC score [combined hyperlipidemia 1.41 (1.06-1.87), hypercholesterolemia 1.55 (1.26 1.92), MetS 1.28 (1.09-1.51), and low HDL-c 1.20 (1.02-1.40)]. Conclusion: Combined hyperlipidemia, simple hypercholesterolemia, MetS, and low HDL-c were associated with multivessel coronary artery disease independent of CVD risk factors and CAC score. These findings may lay the groundwork for further analysis of the underlying mechanisms in the observed relationship, as well as for the development of clinical strategies for primary prevention. PMID- 29785309 TI - Colopancreatic Fistula: An Uncommon Complication of Recurrent Acute Pancreatitis. AB - Colonic complications, including colopancreatic fistulas (CPFs), are uncommon after acute and chronic pancreatitis. However, they have been reported and are serious. CPFs are less likely to close spontaneously and are associated with a higher risk of complications. Therefore, more definitive treatment is required that includes surgical and endoscopic options. We present a case of a 62-year-old male patient with a history of heavy alcohol intake and recurrent acute pancreatitis who presented with a 6-month history of watery diarrhea and abdominal pain. His abdominal imaging showed a possible connection between the colon and the pancreas. A further multidisciplinary workup by the gastroenterology and surgery teams, including endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and colonoscopy, resulted in a diagnosis of CPF. A distal pancreatectomy and left hemicolectomy were performed, and the diagnosis of CPF was confirmed intraoperatively. The patient showed improvement afterward. PMID- 29785310 TI - A Challenging Case of Kikuchi-Fujimoto Disease Associated with Systemic Lupus Erythematosus and Review of the Literature. AB - Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare disease that is frequently underdiagnosed due to clinical features that are similar to those of non-Hodgkin lymphomas, systemic lupus erythematosus (SLE), or infectious reactive lymphadenopathy. An excisional biopsy is required. We report a young Caucasian female diagnosed with KFD with skin lesions, complicating with SLE. The clinical course, laboratory, and CT findings are described, as are histopathologic features, for a better recognition of this rare disorder in clinical practice. PMID- 29785311 TI - Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features. AB - Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20 84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved. PMID- 29785312 TI - A Case of Progressive Stroke on Posterior Circulation with Transient Bilateral Oculomotor Palsy. AB - Infarction located in the midbrain and pons presents various ophthalmic symptoms, because of the damage of the nuclei that control the movement of internal and external ocular and palpebral muscles. We experienced a case which presented with rare ocular symptoms and course. A 61-year-old man presented with left hemiparesis and dysarthria, bilateral ptosis, and bilateral impaired eyeball movement: right eyeball movement was totally impaired and left could only perform slight adduction. MRI showed fresh stroke in the right thalamus, cerebral crus, and posterior lobe and cuneate lesion on bilateral paramedian portion of the midbrain. MRA showed occlusion in the P1 area of the posterior cerebral artery (PCA). Transesophageal echocardiography (TEE) showed findings of a patent foramen ovale (PFO). These findings suggested cardioembolic stroke as a cause of PCA occlusion and we prescribed rivaroxaban. The patient's eyeball and eyelid movement, only on the left side, was improved imperfectly 2 weeks later. We thought that neurological findings and course of this case may have arisen from dysfunction of the oculomotor nucleus and oculomotor fascicles, and MLF results from the presence of the lesion in paramedian midbrain and pons. PMID- 29785313 TI - Management of an Infected Nonunion of an Opening-Wedge High Tibial Osteotomy with 2-Stage Implantation of Rotating Hinge Knee Prosthesis. AB - Introduction: High tibial osteotomy (HTO) is a frequent and effective treatment for unicompartmental gonarthritis. Only a few articles are focused on the treatment of infected nonunion. Patient and Method: A 50-year-old obese patient was operated on by medial opening-wedge HTO. She developed a painful nonunion treated by hardware removal, allograft, and plate fixation. However, the nonunion persisted. 2 years later, cellulitis appeared with an abscess adjacent to the HTO plate. Despite surgical debridement and antibiotics, septic knee arthritis occurred. In a situation of infected nonunion and septic arthritis with chondrolysis, she was scheduled for a 2-stage total knee replacement (TKR). The infected tibial articular block was first resected and replaced by a cement spacer. After a short interval, the TKR was implanted. After 2 years, the patient walked pain-free with good knee function. Discussion: In the literature, different efficient treatments exist for infected nonunion after HTO, but comprehensive studies are missing for a consensus treatment. Current data are mostly based on case reports, since this pathology is quite rare. Conclusion: In a difficult situation of infected nonunion with septic knee arthritis, we performed a 2-stage knee prosthesis implantation. This led to an early mobilization and fast recovery. PMID- 29785314 TI - Osteochondroma of the Scapula with Accessory Nerve (XI) Compression. AB - Osteochondroma is the most common benign bone tumor and is characterized as a cartilage-capped bony stalk. This lesion usually develops from the growth plate of long bones. Most osteochondromas are asymptomatic. Neurovascular compressions or cosmetic issues can occur in specific locations. Malignant transformation is extremely rare, and MRI can help evaluate these lesions. Symptomatic mass and malignancy features are the main surgical indications. Uncommonly, an osteochondroma can develop from flat bones. We present the case of a 25-year-old patient with a right scapula osteochondroma causing an accessory nerve compression. The mass was surgically removed, and the diagnosis was confirmed. The patient fully recovered at the latest 3-year follow-up visit. PMID- 29785315 TI - A Very Rare Case of Hypereosinophilic Syndrome Secondary to Natural Killer/T-Cell Lymphoma. AB - Hypereosinophilic syndrome (HES) is a systemic disease characterized by an increased peripheral blood eosinophil count accompanied by systemic organ dysfunction. HES is classified into idiopathic HES, primary (neoplastic) HES (HESN), and secondary (reactive) HES (HESR). In this case report, a patient who developed peripheral blood eosinophilia and granulation tissue in the pharynx and paranasal sinus, which was initially diagnosed as chronic eosinophilic leukemia (CEL), categorized as HESN, but was eventually identified after the patient had died as natural killer/T-cell (NK/T) lymphoma, nasal type (ENKL), categorized as HESR, is presented. ENKL-induced HES is very rare but must be considered. PMID- 29785316 TI - A Pediatric Case of Relapsing-Remitting Multiple Sclerosis Onset following Varicella Zoster Ophthalmicus with Optic Neuritis. AB - Some epidemiological studies have implied a pathogenetic association between varicella zoster virus (VZV) and multiple sclerosis (MS); this, however, remains controversial. The present report describes a case involving an immunocompetent 10-year-old girl who developed relapsing-remitting MS following the prolonged reactivation of VZV inside the first branch of the trigeminal nerve, exhibiting herpes zoster ophthalmicus with severe optic neuritis. Symptoms related to herpes zoster ophthalmicus and MS appeared consecutively in the 10-week period after the appearance of vesicles. This suggests that the onset of MS was triggered by some mechanism involving VZV reactivation in the first branch of the trigeminal nerve. To the best of our knowledge, this report is the first to describe a relationship between the onset of MS and herpes zoster ophthalmicus. Early diagnosis and aggressive antiviral therapy are important in cases of herpes zoster ophthalmicus to prevent the possible development of MS as well as visual impairment as sequela. PMID- 29785317 TI - A Rare Case of Penile Metastases as a Harbinger of Primary Pulmonary Adenosquamous Carcinoma. AB - Although lung cancer has a high propensity for distant metastatic disease, penile metastases from primary lung neoplasms are considered particularly rare. A 71 year-old male presented to our hospital with a rapidly enlarging hard palpable penile mass. MR imaging demonstrated two penile masses centered in the left and right corpus cavernosa. Subsequent CT imaging revealed a spiculated pulmonary mass in the right upper lobe with PET/CT, MRI, and surgical exploration, demonstrating evidence of metastases to the left adrenal gland, right subscapularis muscle, brain, and small bowel. Tissue sampling of lesions in the small bowel, right subscapularis muscle, and penis demonstrated histopathology consistent with an adenosquamous carcinoma which in combination with the appearance of the right upper lobe mass on PET/CT imaging suggested the patient's lung cancer as the primary lesion. Prior to our case, pulmonary adenosquamous carcinoma metastasizing to the penis has only been reported once in the literature. Herein, we report a rare case of penile metastases as the presenting sign of metastatic pulmonary adenosquamous carcinoma characterized with PET/CT and MR imaging. PMID- 29785318 TI - Role of Nanotechnology in Cosmeceuticals: A Review of Recent Advances. AB - Nanotechnology manifests the progression in the arena of research and development, by increasing the efficacy of the product through delivery of innovative solutions. To overcome certain drawbacks associated with the traditional products, application of nanotechnology is escalating in the area of cosmeceuticals. Cosmeceuticals are regarded as the fastest growing segment of the personal care industry and the use has risen drastically over the years. Nanocosmeceuticals used for skin, hair, nail, and lip care, for conditions like wrinkles, photoaging, hyperpigmentation, dandruff, and hair damage, have come into widespread use. Novel nanocarriers like liposomes, niosomes, nanoemulsions, microemulsion, solid lipid nanoparticles, nanostructured lipid carrier, and nanospheres have replaced the usage of conventional delivery system. These novel nanocarriers have advantages of enhanced skin penetration, controlled and sustained drug release, higher stability, site specific targeting, and high entrapment efficiency. However, nanotoxicological researches have indicated concern regarding the impact of increased use of nanoparticles in cosmeceuticals as there are possibilities of nanoparticles to penetrate through skin and cause health hazards. This review on nanotechnology used in cosmeceuticals highlights the various novel carriers used for the delivery of cosmeceuticals, their positive and negative aspects, marketed formulations, toxicity, and regulations of nanocosmeceuticals. PMID- 29785319 TI - A multi-faceted pandemic: a review of the state of knowledge on the Zika virus. AB - While until recently the small and isolated Zika outbreaks in Eastern Asia and Pacific islands had been overlooked, the large-scale outbreak that started in Brazil in 2015 and the increase of microcephaly cases in the same place and time made media headlines. Considered as harmless until recently, Zika has given rise to an important global crisis that poses not only health challenges but also environmental, economical, social, and ethical challenges for states and people around the world. The main objective of this paper is to review the recent Zika outbreak by covering a broad range of disciplines and their interactions. This paper synthetises experts' interviews and reactions conducted during a Massive Open Online Course (MOOC) entitled "In the footsteps of Zika...approaching the unknown." It reviews knowledge and uncertainties around epidemiology, geographical dispersion of the virus and its vectors through globalization and climate change, and also its modes of transmission, diagnosis, symptoms, and treatment of the disease. The resulting societal and ethical issues in pregnancy and women of reproductive age were also addressed as well as the global outbreak alert and response network in international organizations and social media. This paper attempted to combine each piece of the jigsaw puzzle of the Zika phenomenon to complete the best realistic picture, while keeping in mind the balance between the interdisciplinary nature and international context of Zika and its unique characteristics. PMID- 29785321 TI - Comment on: Screening for malignant melanoma-a critical assessment in historical perspective. PMID- 29785320 TI - Iron-Catalyzed Direct Olefin Diazidation via Peroxyester Activation Promoted by Nitrogen-Based Ligands. AB - We herein report an iron-catalyzed direct diazidation method via activation of bench-stable peroxyesters promoted by nitrogen-based ligands. This method is effective for a broad range of olefins and N-heterocycles, including those that are difficult substrates for the existing olefin diamination and diazidation methods. Notably, nearly a stoichiometric amount of oxidant and TMSN3 are sufficient for high-yielding diazidation for most substrates. Preliminary mechanistic studies elucidated the similarities and differences between this method and the benziodoxole-based olefin diazidation method previously developed by us. This method effectively addresses the limitations of the existing olefin diazidation methods. Most notably, previously problematic nonproductive oxidant decomposition can be minimized. Furthermore, X-ray crystallographic studies suggest that an iron-azide-ligand complex can be generated in situ from an iron acetate precatalyst and that it may facilitate peroxyester activation and the rate-determining C-N3 bond formation during diazidation of unstrained olefins. PMID- 29785322 TI - Periumbilical perforating pseudoxanthoma elasticum: a rare case report. AB - Periumbilical perforating pseudoxanthoma elasticum (PPPXE) usually presents with well-defined periumbilical yellowish atrophic plaques with keratotic papules at the periphery. It is considered a variant of hereditary pseudoxanthoma elasticum or a localized acquired cutaneous dermatosis. The lesions usually occur in the periumbilical area in obese, multiparous women. Here, we report an additional case of periumbilical perforating pseudoxanthoma elasticum with its dermoscopic features. PMID- 29785323 TI - Coexistence of urticaria pigmentosa and thalassemia minor in a young adult. PMID- 29785324 TI - Staphylococcus aureus is the most common bacterial agent of the skin flora of patients with seborrheic dermatitis. AB - Background: Seborrheic dermatitis is an inflammatory skin disease that affects 1 3% of the general population. The Malassezia species has been implicated as the main causative agent; however, the bacterial flora of the skin may also play role in the etiopathogenesis. Therefore, we investigated the most common bacterial agent of the skin flora of patients with seborrheic dermatitis. Materials and Methods: Fifty-one patients with seborrheic dermatitis and 50 healthy individuals are included in this study. Sterile cotton swabs were rubbed on the scalp of the participants for bacterial culture. Colonial morphology was identified with gram stain and catalase test. Results: Staphylococcus aureus was isolated from 25 (49%) patients with seborrheic dermatitis and 10 (20%) healthy individuals within the control group. Coagulase-negative staphylococci were isolated from 24 (47.1%) patients with seborrheic dermatitis and 17 (34%) healthy individuals within the control group. Diphtheroids were present in 2 (3.9%) patients and 1 (2%) subject within the control group. Gram-negative bacilli were present only in 1 (2%) patient. Hemolytic streptococci and bacilli were identified in 1 (2%) subject from each group. Colonization of coagulase-negative staphylococci, diphtheroids, gram-negative bacilli, hemolytic streptococci, and bacillus did not differ between patients and healthy controls. However, S. aureus colonization was significantly more common in patients with seborrheic dermatitis than in healthy controls. Conclusion: Within this study we revealed that S. aureus colonization was significantly higher among the patients. Therefore, we propose that, in addition to the Malassezia species, S. aureus may play a role in the etiopathogenesis of seborrheic dermatitis. PMID- 29785326 TI - Morphologic characteristics of nevi associated with melanoma: a clinical, dermatoscopic and histopathologic analysis. AB - Background: The aim of this retrospective study was to determine the frequency of nevus-associated melanomas and to better characterize the preexisting nevus from a histopathologic, clinical and dermatoscopic point of view. Methods: We reviewed the histopathologic slides of a consecutive series of 357 melanomas and corresponding clinical and dermatoscopic images, if available. Results: We found that 31 (8.7%) melanomas were associated with a preexisting nevus, 284 (79.5%) melanomas developed de novo, and in 42 (11.8%) a preexisting nevus could not be excluded, although the alternative explanation that the entire lesion represented a melanoma was also possible. The preexisting nevus was a "superficial" or "superficial and deep" congenital nevus in 27 cases (87%) and a Clark nevus in 4 cases (13%). Clinical or dermatoscopic images were available in 149 (41.7%) cases. The preexisting nevus, if visible, looked inconspicuous clinically or dermatoscopically. The median invasion thickness of nevus-associated melanoma was not significantly different from "de novo" melanomas but the frequency of in situ melanomas was higher in the "de novo" group (40.1% versus 16.1%). Patients with melanoma in association with a nevus were significantly younger (mean age=55 years, SD: 16 years) than patients with "de novo" melanomas (mean age=68 years SD: 15 years, p<0.001). When controlled for age and invasion thickness overall, survival did not differ significantly between patients with nevus-associated melanomas and patients with de novo melanomas. Conclusions: From a histomorphologic point of view, the majority of melanomas arise de novo. If melanomas develop in a preexisting nevus, they usually occur in association with a "superficial" or "superficial and deep" congenital nevus. PMID- 29785325 TI - Screening for malignant melanoma-a critical assessment in historical perspective. AB - Screening for melanoma has been advocated for many years because early detection and excision have been regarded as the most important measure to lower mortality from that neoplasm. In the past decade, concern has been raised by epidemiologists that screening might result in excision chiefly of "inconsequential cancer," i.e., melanomas that would never have progressed into life-threatening tumors, a phenomenon referred to by the misleading term "overdiagnosis." Without any firm evidence, that speculation has been embraced worldwide, and incipient melanomas have been trivialized. At the same time, efforts at early detection of melanoma have continued and have resulted in biopsy of pigmented lesions at a progressively earlier stage, such as lesions with a diameter of only 2, 3, or 4 mm. Those tiny lesions often lack sufficient criteria for clinical and histopathologic diagnosis, the result being true overdiagnoses, i.e., misdiagnoses of melanocytic nevi as melanoma. This is especially true if available criteria for histopathologic diagnosis are diminuished even further by incomplete excision of lesions. The reliability of histopathologic diagnosis is far higher in excisional biopsies of lesions that were given some more time to develop changes that make them recognizable. Biopsy of pigmented lesions with a diameter of 6 mm has been found to result in a far higher yield of melanomas. In addition to better clinical judgment, slight postponement of biopsies bears the promise of substantial improvement of the reliability of histopathologic diagnosis, and of alleviating true overdiagnoses. PMID- 29785327 TI - Ex vivo confocal microscopy: an emerging technique in dermatology. AB - This review aims to give an overview of the current available applications of ex vivo confocal microscopy (EVCM) in dermatology. EVCM is a relatively new imaging technique that allows microscopic examination of freshly excised unfixed tissue. It enables a rapid examination of the skin sample directly in the surgery room and thus represents an alternative to the intraoperative micrographic control of the surgical margins of cutaneous tumors by standard microscopic examination on cryopreserved sections during Mohs surgery. Although this technique has mainly been developed for the margin's control of basal cell carcinoma, many other skin tumors have been studied, including melanoma. Use of EVCM is continuing to evolve, and many possible applications are under investigation, such as the study of nails and hair diseases and the diagnosis of skin infections. PMID- 29785328 TI - Dermoscopy of a solitary storiform collagenoma. AB - The dermoscopic features of solitary storiform collagenomas (sclerotic fibromas) have not been described previously, as these are rare cutaneous soft tissue tumors. The presence of multiple lesions is considered a marker of Cowden syndrome. They can also present as single firm cutaneous nodules. We present an unusual single nodule with distinct dermoscopic and histologic features. PMID- 29785329 TI - Mycosis fungoides in a 15-year-old adolescent. PMID- 29785330 TI - Dermoscopy of a Spark's nevus. AB - Spark's nevus is a particular type of melanocytic nevus that on histology shows features of both Spitz's and Clark's nevus. Clinically, it is an asymmetric, irregular, multicolored, pigmented lesion that is not clearly distinguishable from melanoma or dysplastic (Clark's) nevus. Dermoscopic features have not been described yet, and one could speculate that they are similar to those of Clark's nevi because the histopathologic architecture of Spark's nevus is similar to that of a Clark's nevus, resembling Spitz's nevi in the epithelioid morphology of melanocytes. We present a 32-year-old woman with a Spark's nevus, who upon dermoscopy showed a pronounced atypical network with accentuation of the blue veil and mostly peripheral dots. PMID- 29785331 TI - Nodular basal cell carcinoma of the face successfully treated with ingenol mebutate 0.015% gel. AB - Surgical excision is the first-choice treatment for basal cell carcinoma (BCC). Other treatments with topical agents such as 5-fluorouracil or imiquimod have also been suggested for use in superficial BCC (sBCC). Ingenol mebutate (IM) is a novel agent employed in the treatment of superficial actinic keratoses. The drug has been also successfully used in the treatment of sBCC. A case of large nodular BCC (nBCC) of the face in a 100-year-old inoperable woman is described. IM 0.015% gel was applied once daily for three consecutive days. This dose regimen was repeated for seven rounds within 11 months, with complete cure of the tumor. Mild local skin reactions, which were tolerated well, were observed. Selected cases of nBCC could be treated with IM gel, but the optimal concentration of the drug and the standard dose regimen of treatment are yet to be determined. PMID- 29785332 TI - Dermoscopic changes in melanocytic nevi covered with both opaque tape and sunscreen cream during narrowband ultraviolet B therapy. AB - Background: Ultraviolet (UV) light may cause dermoscopic changes on melanocytic nevi (MN). Objectives: To investigate the effects of sunscreen cream (SSc) application on dermoscopic changes in MN during narrowband UVB (NBUVB) therapy. Methods: Half of the randomly selected MN in each patient were covered with opaque tape and SSc [SSc(+)], and the rest were covered with only opaque tape [SSc(-)] during NBUVB treatment sessions. Results: More SSc(-) MN displayed dermoscopic changes at end of NBUVB therapy compared to the start of therapy (p=0.035). The number of the MN that decreased in size and showed loss of structure was significantly higher in SSc(-) MN (p=0.04 and p=0.026, respectively). Conclusions: Sunscreen in combination with opaque tape may contribute to some dermoscopic changes in melanocytic nevi, including decrease in size and loss of structure. PMID- 29785333 TI - Acral lentiginous melanoma in the Turkish population and a new dermoscopic clue for the diagnosis. AB - Background: The incidence of acral lentiginous melanoma (ALM) in the white population is low. Dermoscopy enhances diagnosis of ALM; however, diagnostic accuracy may sometimes be poor due to the considerable proportion of amelanotic ALM variants. Objectives: To calculate the proportion of ALM among all melanoma subtypes and to determine the frequency of dermoscopic features of ALM in the Turkish population. Methods: Out of 612 melanomas, there were 70 cases of ALM, of which 46 showed sufficient image quality for retrospective study of dermoscopic features. Data from patients and their lesions was classified according to clinical features and histopathologic parameters. The dermoscopic variables evaluated were based on pertinent literature on dermoscopy of acral melanocytic neoplasms. Results: The prevalence of ALM among all melanoma subtypes was 11.4%. Parallel-ridge pattern (PRP) was detected in 60.8% of cases and irregular diffuse pigmentation (IDP) in 28.3%. The ALMs were amelanotic in 24%, showing an atypical vascular pattern in all cases; a new dermoscopic pattern, named "vascularized parallel-ridge pattern" (VPRP), was detected in 13% of ALMs. Irregular lines were observed in 81.8% of subungual melanomas and were often associated with a multicolored background. Conclusions: ALM has site-specific dermoscopic patterns, with PRP being the most prevalent pattern. The newly described VPRP pattern may be an additional clue for ALM diagnosis, especially in thin amelanotic melanomas. PMID- 29785335 TI - Raised vulvar lesions: be aware! AB - Vulvar melanoma is a rare and deadly cancer in women, and the prognosis is often poor. There are limited studies on the dermoscopic features of vulvar melanoma. Described criteria include the presence of blue, gray, or white colors. Herein we present the clinical and dermoscopic characteristics of a hypopigmented and heavily pigmented nodule in a 92-year-old and an 80-year-old woman. Dermoscopy in the former revealed structureless milky-red to white areas, remnants of brown pigmentation at the base and polymorphic vessels, while the latter displayed structureless blue-gray areas with black dots and peripheral lines at the base. In both cases, histopathology revealed a stage III melanoma. Our two cases along with a review of the literature suggest that the dermoscopic features described for diagnosing cutaneous nodular melanoma, apply also for vulvar melanoma. Clinicians should always raise the suspicion if observing plaques or nodules with a dermoscopic polymorphic vascular pattern and blue-black color on the genitals of postmenopausal women. PMID- 29785334 TI - Radiotherapy for inoperable Merkel cell carcinoma: a systematic review and pooled analysis. AB - Background: Cumulative data on radiation monotherapy for Merkel cell carcinoma (MCC) is lacking. Objective: We sought to synthesize all available data on treatment outcomes for radiation monotherapy for inoperable stage I-III MCC. Methods: We performed a systematic review of the current literature. Articles published in English in the PubMed database up to July 29, 2016, were evaluated. Results: Eight case reports, 4 case series, and 6 retrospective studies, yielding 68 patients, were included in our analysis. Of the 24 stage I/II patients treated with local irradiation, 6 (25%) relapsed and 1 (4%) died from MCC. Of the 24 stage I/II patients treated with local and regional nodal irradiation, 5 (21%) relapsed and 2 (8%) died from MCC. Of the 20 stage III patients treated with local and regional nodal irradiation, 12 (60%) relapsed and 7 (35%) died from MCC. Conclusions: Radiation monotherapy appears to be a reasonable treatment modality for patients with inoperable stage I-III MCC. Further investigation with prospective studies is needed to draw definitive conclusions. PMID- 29785337 TI - Modelling the growth of the brown frog (Rana dybowskii). AB - Well-controlled development leads to uniform body size and a better growth rate; therefore, the ability to determine the growth rate of frogs and their period of sexual maturity is essential for producing healthy, high-quality descendant frogs. To establish a working model that can best predict the growth performance of frogs, the present study examined the growth of one-year-old and two-year-old brown frogs (Rana dybowskii) from metamorphosis to hibernation (18 weeks) and out hibernation to hibernation (20 weeks) under the same environmental conditions. Brown frog growth was studied and mathematically modelled using various nonlinear, linear, and polynomial functions. The model input values were statistically evaluated using parameters such as the Akaike's information criterion. The body weight/size ratio (Kwl) and Fulton's condition factor (K) were used to compare the weight and size of groups of frogs during the growth period. The results showed that the third- and fourth-order polynomial models provided the most consistent predictions of body weight for age 1 and age 2 brown frogs, respectively. Both the Gompertz and third-order polynomial models yielded similarly adequate results for the body size of age 1 brown frogs, while the Janoschek model produced a similarly adequate result for the body size of age 2 brown frogs. The Brody and Janoschek models yielded the highest and lowest estimates of asymptotic weight, respectively, for the body weights of all frogs. The Kwl value of all frogs increased from 0.40 to 3.18. The K value of age 1 frogs decreased from 23.81 to 9.45 in the first four weeks. The K value of age 2 frogs remained close to 10. Graphically, a sigmoidal trend was observed for body weight and body size with increasing age. The results of this study will be useful not only for amphibian research but also for frog farming management strategies and decisions. PMID- 29785336 TI - Targeting the Microbiota, from Irritable Bowel Syndrome to Mood Disorders: Focus on Probiotics and Prebiotics. AB - Purpose of review: The crosstalk between the gut and the brain has revealed a complex communication system responsible for maintaining a proper gastrointestinal homeostasis as well as affect emotional mood and cognitive functions. Recent research has revealed that beneficial manipulation of the microbiota by probiotics and prebiotics represent an emerging and novel strategy for the treatment of a large spectrum of diseases ranging from visceral pain to mood disorders. The review critically evaluates current knowledge of the effects exerted by both probiotics and prebiotics in irritable bowel syndrome (IBS) and mood disorders such as anxiety and depression. Recent findings: Relevant literature was identified through a search of MEDLINE via PubMed using the following words, "probiotics", "prebiotics", "microbiota", and "gut-brain axis" in combination with "stress", "depression", "IBS", and "anxiety". A number of trials have shown efficacy of probiotics and prebiotics in ameliorating both IBS related symptoms and emotional states. However, limitations have been found especially due to the small number of clinical studies, studies design, patient sample size, and placebo effect. Summary: Nonetheless, current finding supports the view that beneficial manipulation of the microbiota through both probiotics and prebiotics intake represents a novel attractive strategy to treat gut-brain axis disorders such as IBS and depression. PMID- 29785338 TI - Coarse- and fine-scale patterns of distribution and habitat selection places an Amazonian floodplain curassow in double jeopardy. AB - Patterns of habitat selection are influenced by local productivity, resource availability, and predation risk. Species have taken millions of years to hone the macro- and micro-habitats they occupy, but these may now overlap with contemporary human threats within natural species ranges. Wattled Curassow (Crax globulosa), an endemic galliform species of the western Amazon, is threatened by both hunting and habitat loss, and is restricted to white-water floodplain forests of major Amazonian rivers. In this study conducted along the Jurua River, Amazonas, Brazil, we quantified the ranging ecology and fine-scale patterns of habitat selection of the species. We estimated the home range size of C. globulosa using conventional VHF telemetry. To estimate patterns of habitat selection, we used geo-locations of day ranges to examine the extent and intensity of use across the floodplain, which were then compared to a high resolution flood map of the study area. We captured two females and one male, which we monitored for 13 months between September 2014 and September 2015. Average home range size was 283 ha, based on the 95% aLoCoH estimator. Wattled Curassows selected areas of prolonged flood pulses (six to eight months/year) and had a consistent tendency to be near open water, usually in close proximity to river banks and lakes, especially during the dry season. Amazonian floodplains are densely settled, and the small portions of floodplain habitat used by Wattled Curassows are both the most accessible to hunters and most vulnerable to deforestation. As a result, the geographic and ecological distribution of Wattled Curassows places them at much higher extinction risk at multiple spatial scales, highlighting the need to consider habitat preferences within their conservation strategy. PMID- 29785339 TI - Identification of potential crucial genes and pathways associated with vein graft restenosis based on gene expression analysis in experimental rabbits. AB - Occlusive artery disease (CAD) is the leading cause of death worldwide. Bypass graft surgery remains the most prevalently performed treatment for occlusive arterial disease, and veins are the most frequently used conduits for surgical revascularization. However, the clinical efficacy of bypass graft surgery is highly affected by the long-term potency rates of vein grafts, and no optimal treatments are available for the prevention of vein graft restenosis (VGR) at present. Hence, there is an urgent need to improve our understanding of the molecular mechanisms involved in mediating VGR. The past decade has seen the rapid development of genomic technologies, such as genome sequencing and microarray technologies, which will provide novel insights into potential molecular mechanisms involved in the VGR program. Ironically, high throughput data associated with VGR are extremely scarce. The main goal of the current study was to explore potential crucial genes and pathways associated with VGR and to provide valid biological information for further investigation of VGR. A comprehensive bioinformatics analysis was performed using high throughput gene expression data. Differentially expressed genes (DEGs) were identified using the R and Bioconductor packages. After functional enrichment analysis of the DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were performed. Finally, nine potential hub genes and fourteen pathways were identified. These hub genes may interact with each other and regulate the VGR program by modulating the cell cycle pathway. Future studies focusing on revealing the specific cellular and molecular mechanisms of these key genes and pathways involved in regulating the VGR program may provide novel therapeutic targets for VGR inhibition. PMID- 29785340 TI - Comparing the catch composition, profitability and discard survival from different trammel net designs targeting common spiny lobster (Palinurus elephas) in a Mediterranean fishery. AB - In the Balearic Islands, different trammel net designs have been adopted to promote fisheries sustainability and reduce discards. Here, we compare the catch performance of three trammel net designs targeting the spiny lobster Palinurus elephas in terms of biomass, species composition and revenue from commercial catches and discards. Designs differ in the netting fiber type (standard polyfilament, PMF, or a new polyethylene multi-monofilament, MMF) and the use of a guarding net or greca, a mesh piece intended to reduce discards. Catches were surveyed by an on-board observer from 1,550 netting walls corresponding to 70 nets. The number of marketable species captured indicated that the lobster trammel net fishery has multiple targets, which contribute significantly to the total revenue. The discarded species ranged from habitat-forming species to elasmobranches, but the magnitude of gear-habitat interactions on the long term dynamics of benthos remains unclear. No relevant differences in revenue and weight of discards were detected after Bayesian analyses. However, the species composition of discards was different when using greca. Interestingly, high immediate survival was found for discarded undersized lobsters, while a seven day survival assessment, using captive observation, gave an asymptotic estimate of survival probability as 0.64 (95% CI [0.54-0.76]). Therefore, it is recommended that it would be beneficial for this stock if an exemption from the EU landing obligation regulation was sought for undersized lobsters in the Balearic trammel net fishery. PMID- 29785341 TI - Overwintering temperature and body condition shift emergence dates of spring emerging solitary bees. AB - Solitary bees in seasonal environments must align their life-cycles with favorable environmental conditions and resources; the timing of their emergence is highly fitness relevant. In several bee species, overwintering temperature influences both emergence date and body weight at emergence. High variability in emergence dates among specimens overwintering at the same temperatures suggests that the timing of emergence also depends on individual body conditions. However, possible causes for this variability, such as individual differences in body size or weight, have been rarely studied. In a climate chamber experiment using two spring-emerging mason bees (Osmia cornuta and O. bicornis), we investigated the relationship between temperature, emergence date, body weight, and body size, the last of which is not affected by overwintering temperature. Our study showed that body weight declined during hibernation more strongly in warm than in cold overwintering temperatures. Although bees emerged earlier in warm than in cold overwintering temperatures, at the time of emergence, bees in warm overwintering temperatures had lower body weights than bees in cold overwintering temperatures (exception of male O. cornuta). Among specimens that experienced the same overwintering temperatures, small and light bees emerged later than their larger and heavier conspecifics. Using a simple mechanistic model we demonstrated that spring-emerging solitary bees use a strategic approach and emerge at a date that is most promising for their individual fitness expectations. Our results suggest that warmer overwintering temperatures reduce bee fitness by causing a decrease in body weight at emergence. We showed furthermore that in order to adjust their emergence dates, bees use not only temperature but also their individual body condition as triggers. This may explain differing responses to climate warming within and among bee populations and may have consequences for bee-plant interactions as well as for the persistence of bee populations under climate change. PMID- 29785342 TI - Occurrence of termites (Isoptera) on living and standing dead trees in a tropical dry forest in Mexico. AB - Termites play a key role as ecosystem engineers in numerous ecological processes though their role in the dynamics of wood degradation in tropical dry forests, particularly at the level of the crown canopy, has been little studied. In this study, we analysed the occurrence of termites in the forest canopy by evaluating the density and proportion of living and standing dead trees associated with termites in deciduous and riparian habitats of the tropical dry forest in Chamela, Mexico. The results indicated that 60-98% of standing dead trees and 23 59% of living trees in Chamela were associated with termites. In particular, we found that the density of standing dead trees was higher in deciduous forests (0.057-0.066 trees/m2) than in riparian forests (0.022 and 0.027 trees/m2), even though the proportion of trees was not significantly different among habitats. Additionally, we found a higher density of trees associated with termites in trees of smaller size classes (0.01-0.09 trees/m2) than in larger class sizes (0 0.02 trees/m2). Interestingly, 72% of variation in the density of trees associated with termites is explained by the density of standing dead trees. Overall, these results indicate that standing dead tree availability might be the main factor regulating termite populations in Chamela forest and suggest that termites could play a key role in the decomposition of above-ground dead wood, mediating the incorporation of suspended and standing dead wood into the soil. PMID- 29785343 TI - Perinatal specimens of Maiasaura from the Upper Cretaceous of Montana (USA): insights into the early ontogeny of saurolophine hadrosaurid dinosaurs. AB - Perinatal specimens of hadrosaurids discovered in the late 1970's by field crews from Princeton University were significant in providing evidence of the early ontogenetic stages in North American dinosaurs. These specimens from the Campanian (Upper Cretaceous) Two Medicine Formation of Montana consist of over a dozen skeletons referable to the saurolophine hadrosaurid Maiasaura peeblesorum, but never fully figured or described. Here, we provide a more complete documentation of the morphology of these specimens, along with an examination of variation during a large span of the development of saurolophine hadrosaurids. Many ontogenetic changes in the available facial and mandibular elements are associated with the progressive elongation of the preorbital region of the skull and mandible. In the postcranium, limb bones change nearly isometrically, with exception of certain elements of the forelimb. Some cranial and postcranial characters commonly used for inferring hadrosaurid phylogenetic relationships remain invariable during the ontogeny of M. peeblesorum. This indicates that early ontogenetic stages may still provide a limited amount of character information useful for systematics and phylogenetic inference. PMID- 29785344 TI - Citizen science data suggest that a novel rig improves landing rate and reduces injury and handling time in recreational angling with artificial lures in Baltic pike (Esox lucius). AB - The optimal terminal gear in hook-and-line recreational fishing maximizes landing rates and minimizes injury to the fish because some fish will be released after capture. We designed a novel rig configuration in artificial lure fishing for top predators and examined its effectiveness in angling for Baltic northern pike (Esox lucius) using a citizen science approach based on observational data collected from volunteer anglers in the field. The novel rig included two changes to traditional rig designs common to artificial lure angling. First, hooks were mounted in a way giving better hook exposure and eliminating lever-arm effects from the lure to the hooks once a fish is hooked. This construction allowed the second change, being a shift to hooks 4-5 sizes smaller than those used on traditional hook mounts. We analysed observational data collected by volunteer anglers using either the novel rig or a standard rig mount in two types of artificial lures (softbait and hardbait) of the same size (about 17 cm). Using N = 768 pike contacts as input data, we showed the landing rates of pike targeted with artificial lures significantly and substantially increased from 45% with normal-rigs to 85% when the same lure types were fished with the novel rig configuration. Lure type and water temperature had no effects on landing rates. Moreover, hardbaits on normal-rigs produced significantly more injury, bleeding and elevated unhooking time compared to fish captured on hardbaits with release rigs. We conclude that simple changes to traditional hook sizes and mounts in lure fishing may benefit both anglers and the fishes that are to be released and that citizen science projects with volunteer anglers are able to provide good data in proof-of-concept studies. Further experimental studies are needed to differentiate hook size from hook mount effects because both variables were confounded in the results of the observational data presented here. PMID- 29785345 TI - Greenland shark (Somniosus microcephalus) feeding behavior on static fishing gear, effect of SMART (Selective Magnetic and Repellent-Treated) hook deterrent technology, and factors influencing entanglement in bottom longlines. AB - The Greenland Shark (Somniosus microcephalus) is the most common bycatch in the Greenland halibut (Reinhardtius hippoglossoides) bottom longline fishery in Cumberland Sound, Canada. Historically, this inshore fishery has been prosecuted through the ice during winter but winter storms and unpredictable landfast ice conditions since the mid-1990s have led to interest in developing a summer fishery during the ice-free season. However, bycatch of Greenland shark was found to increase substantially with 570 sharks captured during an experimental Greenland halibut summer fishery (i.e., mean of 6.3 sharks per 1,000 hooks set) and mortality was reported to be about 50% due in part to fishers killing sharks that were severely entangled in longline gear. This study investigated whether the SMART (Selective Magnetic and Repellent-Treated) hook technology is a practical deterrent to Greenland shark predation and subsequent bycatch on bottom longlines. Greenland shark feeding behavior, feeding kinematics, and variables affecting entanglement/disentanglement and release are also described. The SMART hook failed to deter Greenland shark predation, i.e., all sharks were captured on SMART hooks, some with more than one SMART hook in their jaw. Moreover, recently captured Greenland sharks did not exhibit a behavioral response to SMART hooks. In situ observations of Greenland shark feeding show that this species uses a powerful inertial suction mode of feeding and was able to draw bait into the mouth from a distance of 25-35 cm. This method of feeding is suggested to negate the potential deterrent effects of electropositive metal and magnetic alloy substitutions to the SMART hook technology. The number of hooks entangled by a Greenland shark and time to disentangle and live-release a shark was found to increase with body length. PMID- 29785348 TI - Pollution of the sediments of the coastal zone of the Sambia Peninsula and the Curonian Spit (Southeastern Baltic Sea). AB - The detailed environmental survey of the coastal zone of the Kaliningrad Region northern coast was carried out. The pollutants distribution in the silty clay fraction and calculation of ecological indexes allowed the evaluation of distribution of potentially harmful elements (PHEs). The sources of pollution in the most intensively used areas were identified, and transit and accumulation zones were allocated. A large area of anomalous content of PHEs was revealed on the underwater coastal slope of the Curonian Spit National Park, which is situated far from the sources of pollution. The alongshore bed load transport provides the contamination of the underwater slope whereas the beaches are less exposed to pollution. PMID- 29785347 TI - A new species of Pseudopaludicola (Anura, Leiuperinae) from Espirito Santo, Brazil. AB - We describe a new anuran species of the genus Pseudopaludicola that inhabits sandy areas in resting as associated to the Atlantic Forest biome in the state of Espirito Santo, Brazil. The new species is characterized by: SVL 11.7-14.6 mm in males, 14.0-16.7 mm in females; body slender; fingertips knobbed, with a central groove; hindlimbs short; abdominal fold complete; arytenoid cartilages wide; prepollex with base and two segments; prehallux with base and one segment; frontoparietal fontanelle partially exposed; advertisement call with one note composed of two isolated pulses per call; call dominant frequency ranging 4,380 4,884 Hz; diploid chromosome number 22; and Ag-NORs on 8q subterminal. In addition, its 16S rDNA sequence shows high genetic distances when compared to sequences of related species, which provides strong evidence that the new species is an independent lineage. PMID- 29785346 TI - Integrated bioinformatic changes and analysis of retina with time in diabetic rats. AB - Diabetic retinopathy (DR) is the most common chronic complication of diabetes. It can cause impaired vision and even blindness. However, the pathological mechanism of DR is still unknown. In the present study, we use bioinformatic analysis to reveal the pathological changes of early DR in a streptozotocin (STZ) induced diabetes rat model. The dataset GSE28831 was downloaded from the Gene Expression Omnibus (GEO) database. To clarify the pathological mechanism of early DR, genes which were up-regulated (UP group) or down-regulated (DOWN group) over time were identified. One hundred eighty six genes in the UP group and 85 genes in the DOWN group were defined. There were in total 28 Gene ontology (GO) terms with a P value lower than 0.05 in UP group, including astrocyte development, neutrophil chemotaxis, neutrophil aggregation, mesenchymal cell proliferation and so on. In the DOWN group, there were totally 14 GO terms with a P value lower than 0.05, including visual perception, lens development in camera-type eye, camera-type eye development, bicellular tight junction and so on. Signaling pathways were analyzed with all genes in the UP and DOWN groups, and leukocyte transendothelial migration and tight junction were selected. Protein-protein interaction (PPI) network was constructed and six hub genes Diras3, Actn1, Tssk6, Cnot6l, Tek and Fgf4 were selected with connection degree >=5. S100a8, S100a9 and Tek may be potential targets for DR diagnosis and treatment. This study provides the basis for the diagnosis and treatment of DR in the future. PMID- 29785349 TI - Novel, non-symbiotic isolates of Neorhizobium from a dryland agricultural soil. AB - Semi-selective enrichment, followed by PCR screening, resulted in the successful direct isolation of fast-growing Rhizobia from a dryland agricultural soil. Over 50% of these isolates belong to the genus Neorhizobium, as concluded from partial rpoB and near-complete 16S rDNA sequence analysis. Further genotypic and genomic analysis of five representative isolates confirmed that they form a coherent group within Neorhizobium, closer to N. galegae than to the remaining Neorhizobium species, but clearly differentiated from the former, and constituting at least one new genomospecies within Neorhizobium. All the isolates lacked nod and nif symbiotic genes but contained a repABC replication/maintenance region, characteristic of rhizobial plasmids, within large contigs from their draft genome sequences. These repABC sequences were related, but not identical, to repABC sequences found in symbiotic plasmids from N. galegae, suggesting that the non-symbiotic isolates have the potential to harbor symbiotic plasmids. This is the first report of non-symbiotic members of Neorhizobium from soil. PMID- 29785350 TI - The effect of climate change on the distribution of a tropical zoanthid (Palythoa caribaeorum) and its ecological implications. AB - Palythoa caribaeorum is a zoanthid often dominant in shallow rocky environments along the west coast of the Atlantic Ocean, from the tropics to the subtropics. This species has high environmental tolerance and is a good space competitor in reef environments. Considering current and future scenarios in the global climate regime, this study aimed to model and analyze the distribution of P. caribaeorum, generating maps of potential distribution for the present and the year 2100. The distribution was modeled using maximum entropy (Maxent) based on 327 occurrence sites retrieved from the literature. Calcite concentration, maximum chlorophyll-a concentration, salinity, pH, and temperature range yielded a model with the smallest Akaike information criterion (2649.8), and were used in the present and future distribution model. Data from the HadGEM2-ES climate model were used to generate the projections for the year 2100. The present distribution of P. caribaeorum shows that parts of the Brazilian coast, Caribbean Sea, and Florida are suitable regions for the species, as they are characterized by high salinity and pH and small temperature variation. An expansion of the species' distribution was forecast northward under mild climate scenarios, while a decrease of suitable areas was forecast in the south. In the climate scenario with the most intense changes, P. caribaeorum would lose one-half of its suitable habitats, including the northernmost and southernmost areas of its distribution. The Caribbean Sea and northeastern Brazil, as well as other places under the influence of coastal upwellings, may serve as potential havens for this species. PMID- 29785351 TI - Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain. AB - Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in a brain with PD, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra. PMID- 29785352 TI - Diversity and community structure of marine microbes around the Benham Rise underwater plateau, northeastern Philippines. AB - Microbes are central to the structuring and functioning of marine ecosystems. Given the remarkable diversity of the ocean microbiome, uncovering marine microbial taxa remains a fundamental challenge in microbial ecology. However, there has been little effort, thus far, to describe the diversity of marine microorganisms in the region of high marine biodiversity around the Philippines. Here, we present data on the taxonomic diversity of bacteria and archaea in Benham Rise, Philippines, Western Pacific Ocean, using 16S V4 rRNA gene sequencing. The major bacterial and archaeal phyla identified in the Benham Rise are Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, Marinimicrobia, Thaumarchaeota and, Euryarchaeota. The upper mesopelagic layer exhibited greater microbial diversity and richness compared to surface waters. Vertical zonation of the microbial community is evident and may be attributed to physical stratification of the water column acting as a dispersal barrier. Canonical Correspondence Analysis (CCA) recapitulated previously known associations of taxa and physicochemical parameters in the environment, such as the association of oligotrophic clades with low nutrient surface water and deep water clades that have the capacity to oxidize ammonia or nitrite at the upper mesopelagic layer. These findings provide foundational information on the diversity of marine microbes in Philippine waters. Further studies are warranted to gain a more comprehensive picture of microbial diversity within the region. PMID- 29785354 TI - Geographical variation in colour of female threespine stickleback (Gasterosteus aculeatus). AB - The ecological multifunctionality of colour often results in multiple selective pressures operating on a single trait. Most research on colour evolution focuses on males because they are the most conspicuous sex in most species. This bias can limit inferences about the ecological drivers of colour evolution. For example, little is known about population divergence in colour of female threespine stickleback (Gasterosteus aculeatus), which is among the most intensively-studied model vertebrates in evolution, ecology, and behaviour. In contrast, the evolution and ecology of colour in male stickleback has received considerable attention. One aspect of female colouration that is lacking previous research is non-ornamental body colour. Non-ornamental colour can play defensive and social roles, and indicate other aspects of female stickleback ecology. To remedy this knowledge gap, we measured the colour and brightness of one dorsal and one ventral lateral area on female stickleback from nine lake populations on Vancouver Island. We found that lake populations varied in overall colour brightness and dorso-ventral contrast. In addition, we found that female brightness increased with lake size, indicating potential ecological drivers of these colour differences. Our results demonstrate that there is substantial scope for future research on female colour diversification, which has been overlooked because past researchers focused on dramatic male nuptial colours. PMID- 29785353 TI - Diet breadth and exploitation of exotic plants shift the core microbiome of Cephaloleia, a group of tropical herbivorous beetles. AB - The beetle genus Cephaloleia has evolved in association with tropical ginger plants and for many species their specific host plant associations are known. Here we show that the core microbiome of six closely related Costa Rican Cephaloleia species comprises only eight bacterial groups, including members of the Acinetobacter, Enterobacteriacea, Pseudomonas, Lactococcus, and Comamonas. The Acinetobacter and Enterobacteriacea together accounted for 35% of the total average 16S rRNA ribotypes recovered from all specimens. Further, microbiome diversity and community structure was significantly linked to beetle diet breadth, between those foraging on less than two plant types (specialists) versus over nine plant types (generalists). Moraxellaceae, Enterobacteriaceae, and Pseudomonadaceae were highly prevalent in specialist species, and also present in eggs, while Rickettsiaceae associated exclusively with generalist beetles. Bacteria isolated from Cephaloleia digestive systems had distinct capabilities and suggested a possible beneficial role in both digestion of plant-based compounds, including xylose, mannitol, and pectin, and possible detoxification, via lipases. Cephaloleia species are currently expanding their diets to include exotic invasive plants, yet it is unknown whether their microbial community plays a role in this transition. In this study, colonization of invasive plants was correlated with a dysbiosis of the microbiome, suggesting a possible relationship between gut bacteria and niche adaptation. PMID- 29785355 TI - Identification and expression analysis of cytokinin metabolic genes IPTs, CYP735A and CKXs in the biofuel plant Jatropha curcas. AB - The seed oil of Jatropha curcas is considered a potential bioenergy source that could replace fossil fuels. However, the seed yield of Jatropha is low and has yet to be improved. We previously reported that exogenous cytokinin treatment increased the seed yield of Jatropha. Cytokinin levels are directly regulated by isopentenyl transferase (IPT), cytochrome P450 monooxygenase, family 735, subfamily A (CYP735A), and cytokinin oxidase/dehydrogenase (CKX). In this study, we cloned six IPT genes, one JcCYP735A gene, and seven JcCKX genes. The expression patterns of these 14 genes in various organs were determined using real-time quantitative PCR. JcIPT1 was primarily expressed in roots and seeds, JcIPT2 was expressed in roots, apical meristems, and mature leaves, JcIPT3 was expressed in stems and mature leaves, JcIPT5 was expressed in roots and mature leaves, JcIPT6 was expressed in seeds at 10 days after pollination, and JcIPT9 was expressed in mature leaves. JcCYP735A was mainly expressed in roots, flower buds, and seeds. The seven JcCKX genes also showed different expression patterns in different organs of Jatropha. In addition, CK levels were detected in flower buds and seeds at different stages of development. The concentration of N6 (Delta2-isopentenyl)-adenine (iP), iP-riboside, and trans-zeatin (tZ) increased with flower development, and the concentration of iP decreased with seed development, while that of tZ increased. We further analyzed the function of JcCYP735A using the CRISPR-Cas9 system, and found that the concentrations of tZ and tZ-riboside decreased significantly in the Jccyp735a mutants, which showed severely retarded growth. These findings will be helpful for further studies of the functions of cytokinin metabolic genes and understanding the roles of cytokinins in Jatropha growth and development. PMID- 29785357 TI - Prognostic Significance of Cyclins A2, B1, D1, and E1 and CCND1 Numerical Aberrations in Oral Squamous Cell Carcinomas. AB - We analysed the expression of cyclins A2, B1, D1, and E1 by immunohistochemistry and numerical aberrations in CCND1 gene by fluorescence in situ hybridization technique in 67 primary oral squamous cell carcinomas (OSCC). Cyclin A2 expression was observed in 54 (83.1%) tumours, cyclin D1 in 58 (89.2%), cyclin B1 in 39 (60%), and cyclin E in 21 (32.8%). CCND1 region analysis revealed 26 (43.3%) tumours with the presence of numerical aberrations which were correlated with cyclin D1 high expression (Rho = 0.48; p < 0.001). Twenty-nine (45.3%) tumours were classified as high proliferative tumours assessed by Ki-67 protein expression and correlated with tumours with high expression of cyclin A2 (Rho = 0.30; p = 0.016) and cyclin B1 (Rho = 0.37; p = 0.003). In multivariate analysis for an overall five-year survival (OS), we found an adverse independent prognostic value for cyclin A2 high expression (p = 0.031) and for advanced tumour stage (p < 0.001). Our results confirm that several cyclins are commonly expressed in OSCC. CCND1 gene is abnormal in more than one-third of the cases and is frequently associated with cyclin D1 high expression. Moreover, cyclin A2 high expression is an independent indicator of worse OS suggesting that this protein may serve as a reliable biological marker to identify high-risk subgroups with poor prognosis. PMID- 29785356 TI - Examining the potential for South American arboviruses to spread beyond the New World. AB - : Zika and chikungunya viruses emerged as public health emergencies in the Western Hemisphere where previously they had not been reported on a large scale. Millions were infected as the viruses met with virtually no herd immunity upon emergence. Purpose of the Review: We explore the histories of these two recent arbovirus experiences in South America. We then review similarly three endemic South American viruses: yellow fever, Oropouche, and Mayaro viruses. Recent Findings: We discuss the commonalities of the transmission systems and the possibility of an atypical emergence, that of New World virus to the Old World. Summary: We discuss the avenues for research that would increase preparedness and efficiency of response should a South American arbovirus emerge in the Eastern Hemisphere. PMID- 29785358 TI - Bacterial community changes in an industrial algae production system. AB - While microalgae are a promising feedstock for production of fuels and other chemicals, a challenge for the algal bioproducts industry is obtaining consistent, robust algae growth. Algal cultures include complex bacterial communities and can be difficult to manage because specific bacteria can promote or reduce algae growth. To overcome bacterial contamination, algae growers may use closed photobioreactors designed to reduce the number of contaminant organisms. Even with closed systems, bacteria are known to enter and cohabitate, but little is known about these communities. Therefore, the richness, structure, and composition of bacterial communities were characterized in closed photobioreactor cultivations of Nannochloropsis salina in F/2 medium at different scales, across nine months spanning late summer-early spring, and during a sequence of serially inoculated cultivations. Using 16S rRNA sequence data from 275 samples, bacterial communities in small, medium, and large cultures were shown to be significantly different. Larger systems contained richer bacterial communities compared to smaller systems. Relationships between bacterial communities and algae growth were complex. On one hand, blooms of a specific bacterial type were observed in three abnormal, poorly performing replicate cultivations, while on the other, notable changes in the bacterial community structures were observed in a series of serial large-scale batch cultivations that had similar growth rates. Bacteria common to the majority of samples were identified, including a single OTU within the class Saprospirae that was found in all samples. This study contributes important information for crop protection in algae systems, and demonstrates the complex ecosystems that need to be understood for consistent, successful industrial algae cultivation. This is the first study to profile bacterial communities during the scale-up process of industrial algae systems. PMID- 29785359 TI - White matter microstructure, white matter lesions, and hypertension: An examination of early surrogate markers of vascular-related brain change in midlife. AB - Objective: We examined imaging surrogates of white matter microstructural abnormalities which may precede white matter lesions (WML) and represent a relevant marker of cerebrovascular injury in adults in midlife. Methods: In 698 community-dwelling adults (mean age 50 years +/-3.5 SD) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study, WML were identified on structural MR and fractional anisotropy (FA), representing WM microstructural integrity, was derived using Diffusion Tensor Imaging. FA and WML maps were overlaid on a parcellated T1-template, based on an expert-delineated brain atlas, which included 42 WM tract ROIs. Analyses occurred in stages: 1) WML were quantified for the different tracts (i.e., frequency, volume, volume relative to tract size); 2) the interdependence of FA in normal appearing WM (NAWM) and WML was examined across tracts; 3) associations of NAWM FA and hypertension status were assessed controlling for WML volume. In the latter analysis, both overall hypertension (i.e. hypertension vs. normotension and prehypertension vs. normotension) and hypertension categorized by antihypertensive treatment status (yes/no) and blood pressure control (e.g., diastolic <90 mmHg, systolic <140 mmHg), were assessed. Results: WML were widely distributed across different WM tracts, however, WML volume was small. Mean NAWM FA was lower in participants with vs. participants without WML in given tracts. Hypertension was significantly associated with lower mean NAWM FA globally across tracts, both before and after adjustment for WML volume. Moreover, the magnitude of this association differed by treatment status and the level of control of the hypertension. Conclusions: In middle-aged adults, NAWM FA could represent a relevant marker of cerebrovascular injury when WML are minimally present. PMID- 29785361 TI - Air bubbles in the urinary tract. Incidental and asymptomatic combined emphysematous pyelitis, ureteritis and cystitis. A rare case report and review of the literature. PMID- 29785362 TI - The half-loop transurethral incision technique for bilateral ureterocele in adult. PMID- 29785360 TI - Identical patterns of cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A tract of interest-based MRI study. AB - Background: There is an ongoing debate whether primary lateral sclerosis (PLS) should be regarded as an independent disease entity separate from amyotrophic lateral sclerosis (ALS) or as a slowly progressive variant of ALS. Objective: The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PLS patients by a hypothesis-guided tract-of interest-based approach compared with 'classical' ALS patients and healthy controls, in order to identify microstructural changes according to the neuropathologically defined ALS affectation pattern in vivo. Methods: DTI-based white matter mapping was performed both by an unbiased voxelwise statistical comparison and by a hypothesis-guided tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 50 PLS and 50 ALS patients vs 50 matched controls. Results: The analysis of white matter integrity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in PLS patients and ALS patients. In the tract-specific analysis according to the ALS-staging pattern, PLS and ALS affectation patterns showed identical significant alterations of ALS-related tract systems when compared with controls and no differences when compared with each other. Conclusions: This DTI study showed the same microstructural affectation patterns in PLS patients as in ALS, in support of the hypothesis that PLS is a phenotypical variant of ALS. PMID- 29785363 TI - An unlikely connection: Rare case of colo-urachal fistula, surgical management, and review of the literature. PMID- 29785364 TI - Neo-glans reconstruction after glans amputation during circumcision using autologous buccal mucosal graft. PMID- 29785366 TI - Co-existing renal myelolipoma and renal cell carcinoma: A case report. PMID- 29785365 TI - Isolated primary schwannoma of the urinary bladder- a case presentation. PMID- 29785367 TI - Retroperitoneal cystic lymphangioma in an adult: A case report. PMID- 29785368 TI - Case of perinephric abscess disguising as renal tumor. PMID- 29785369 TI - A rare highly aggressive tumor of the kidney: The pure epithelioid angiomyolipoma. PMID- 29785370 TI - Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report. AB - We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment. PMID- 29785371 TI - Case report: Clitoromegaly as a consequence of Congenital Adrenal Hyperplasia. An accurate medical and surgical approach. AB - We present a case of a woman with a history of Congenital Adrenal Hyperplasia (CAH) diagnosed at the age of 12, who was referred to our unit for surgical treatment. Despite the initial diagnosis was an indirect inguinal hernia, it was a misdiagnosis. Once in our service, this was corrected into clitoromegaly secondary to CAH. Physical examination and imaging test discarded other abnormalities, such as secondary effects androgenization. Regarding surgical treatment, the techniques used were Spencer and Allen combined with Kumar, which are the most used for clitoroplasty but also less used in Peru. PMID- 29785372 TI - What is the role of nephrectomy following complete response to checkpoint inhibitors? PMID- 29785373 TI - Primary bladder adenocarcinoma: Case report with long-term follow-up. AB - Primary Bladder Adenocarcinoma is a rare malignancy that has been observed in a heterogeneous patient population. This case report presents a 51 year old female with muscle-invasive primary bladder adenocarcinoma diagnosed in 2008. After transurethral resection and cystectomy with ileum neobladder adjuvant radiochemotherapy was administered. Two years later, a symptomatic fistula between neobladder and ileoileal anastomosis was excised, resulting in urinary incontinency. In 2016, the patient shows no signs of disease relapse but suffers from reduction of bladder capacity. This case report presents classical symptoms of adenocarcinoma of the bladder and a possible treatment regimen with associated side effects. PMID- 29785375 TI - Cross fused renal ectopia with associated renal cell carcinoma. PMID- 29785374 TI - Giant bilateral adrenal myelolipoma:Case presentation and a brief literature review. PMID- 29785376 TI - Urinary retention in a hypospadiac failure secondary to urethral calculi. PMID- 29785377 TI - Cobb's collar and chronic renal failure. PMID- 29785379 TI - Robotic-assisted laparoscopic vesiculectomy in a patient with atypical Zinner syndrome presenting with large cyst involving bilateral seminal vesicles and vasa deferentia. PMID- 29785378 TI - Delayed presentation of grade-IV renal injury post blunt trauma. AB - High-grade renal injuries are relatively uncommon in blunt trauma. They typically occur in the context of multisystem injuries. When present, these renal injuries are usually identified at the time of hospital presentation. Here, we present a case of delayed presentation of American Association for the Surgery of Trauma (AAST) grade-IV renal injury in a 61-year-old female who sustained multisystem injuries during a high-speed motor vehicle accident. To our knowledge, this is the first report case of delayed presentation of grade-IV renal injury. This case highlights the importance of serial examination and repeated imaging in complex trauma patients. PMID- 29785380 TI - Urethroperineal fistula in a patient with a stone in a bulbar diverticulum after a scrotal skin flap urethroplasty: A case report. PMID- 29785382 TI - Matador injury case report: Spermatic cord fat pad (SCFP) interposition to support complex pelvic reconstruction-a novel technique. PMID- 29785381 TI - Primary renal large B-cell lymphoma imitating invasive renal cell carcinoma with inferior vena cava tumor thrombus. PMID- 29785383 TI - Valentine's day misadventure: Missing vagina for urethra. PMID- 29785384 TI - Unilateral complete ureteral duplication with calculi obstructing both limbs of the left side. PMID- 29785386 TI - Diet and lifestyle for post-reproductive health: Focus on diabetes. PMID- 29785387 TI - Parvovirus B19 infection: Timely diagnosis in pregnancy essential. PMID- 29785385 TI - Malakoplakia of the prostate diagnosed on multiparametric-MRI ultrasound fusion guided biopsy: A case report and review of the literature. PMID- 29785388 TI - Genital tuberculosis in postmenopausal women with variable clinical presentations: A report of 3 cases. AB - Genital tuberculosis is usually diagnosed in young women being assessed for infertility. After menopause it usually presents with symptoms resembling endometrial malignancy, such as postmenopausal bleeding, persistent vaginal discharge and pyometra. The diagnosis is made by detection of acid-fast bacilli on microscopy or bacteriological culture and/or presence of epithelioid granuloma on biopsy. Anti-tubercular therapy involves the use of rifampicin, isoniazid, pyrazinamide and ethambutol. Surgery is indicated if a pelvic mass and recurrence of pain or bleeding persist after 9 months of treatment. Three cases of genital tuberculosis in postmenopausal women with different clinical presentations are reported. The first woman presented with ascites and weight loss. The second had postmenopausal bleeding with a pipelle biopsy suggestive of endometrial intraepithelial neoplasia. The third presented with weight loss and a palpable abdominal mass. Pelvic malignancy was initially suspected but a diagnosis of tuberculosis was made following pre-operative endometrial biopsy, bacteriological culture and intra-operative frozen section. All three women responded to anti tubercular therapy. PMID- 29785389 TI - Pelvic and pulmonary benign metastasizing leiomyoma: A case report. AB - Seven years after she had a total abdominal hysterectomy for benign leiomyomas, a 46-year-old woman presented with a pelvic mass and multiple pulmonary nodules. She underwent resection of the mass and core needle biopsy of a pulmonary lesion. Histopathologic analysis revealed that both the pelvic and the pulmonary lesions were consistent with benign leiomyomas. Benign metastasizing leiomyoma should be considered if a woman of reproductive age and with a history of leiomyomas presents with extrauterine nodules without evidence of malignancy. The final diagnosis should be based on histopathological examination. Treatment depends on tumor size, location, receptor positivity, and disease progression. PMID- 29785390 TI - Platelet-rich plasma (PRP) for the treatment of vulvar lichen sclerosus in a premenopausal woman: A case report. AB - The use of platelet-rich plasma (PRP) for the treatment of lichen sclerosus (LS) in a 38-year-old premenopausal woman is reported. The diagnosis was confirmed histologically and the symptoms documented using the ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS) and the Female Sexual Function Index (FSFI) questionnaire. PRP was prepared from autologous blood using the Regen Cellular Matrix Kit. PRP was administered twice over two months. Histology at follow-up one month after the second administration showed the epidermis was nearly normal and upper dermal cellularity had been restored. The patient was symptom-free and both her ICIQ-VS and her FSFI scores had improved significantly. PRP is a potential new treatment option for LS which needs further assessment in randomized controlled trials. PMID- 29785391 TI - How Monte Carlo heuristics aid to identify the physical processes of drug release kinetics. AB - We implement a Monte Carlo heuristic algorithm to model drug release from a solid dosage form. We show that with Monte Carlo simulations it is possible to identify and explain the causes of the unsatisfactory predictive power of current drug release models. It is well known that the power-law, the exponential models, as well as those derived from or inspired by them accurately reproduce only the first 60% of the release curve of a drug from a dosage form. In this study, by using Monte Carlo simulation approaches, we show that these models fit quite accurately almost the entire release profile when the release kinetics is not governed by the coexistence of different physico-chemical mechanisms. We show that the accuracy of the traditional models are comparable with those of Monte Carlo heuristics when these heuristics approximate and oversimply the phenomenology of drug release. This observation suggests to develop and use novel Monte Carlo simulation heuristics able to describe the complexity of the release kinetics, and consequently to generate data more similar to those observed in real experiments. Implementing Monte Carlo simulation heuristics of the drug release phenomenology may be much straightforward and efficient than hypothesizing and implementing from scratch complex mathematical models of the physical processes involved in drug release. Identifying and understanding through simulation heuristics what processes of this phenomenology reproduce the observed data and then formalize them in mathematics may allow avoiding time consuming, trial-error based regression procedures. Three bullet points, highlighting the customization of the procedure. *An efficient heuristics based on Monte Carlo methods for simulating drug release from solid dosage form encodes is presented. It specifies the model of the physical process in a simple but accurate way in the formula of the Monte Carlo Micro Step (MCS) time interval.*Given the experimentally observed curve of drug release, we point out how Monte Carlo heuristics can be integrated in an evolutionary algorithmic approach to infer the mode of MCS best fitting the observed data, and thus the observed release kinetics.*The software implementing the method is written in R language, the free most used language in the bioinformaticians community. PMID- 29785392 TI - Periosteal pseudotumor in complex total knee arthroplasty resembling a neoplastic process. AB - This case report describes in detail an erosive distal diaphyseal pseudotumor that occurred 6 years after a complex endoprosthetic hinge total knee arthroplasty (TKA). A female patient had conversion of a knee fusion to an endoprosthetic hinge TKA at the age of 62. At her scheduled 6-year follow-up, she presented with mild distal thigh pain and radiographs showing a 6-7 cm erosive lytic diaphyseal lesion that looked very suspicious for a neoplastic process. An en bloc resection of the distal femur and femoral endoprosthesis was performed. Histologic review showed the mass to be a pseudotumor with the wear debris emanating from within the femoral canal due to distal stem loosening. We deduce that mechanized stem abrasion created microscopic titanium alloy particles that escaped via a small diaphyseal crack and stimulated an inflammatory response resulting in a periosteal erosive pseudotumor. The main lesson of this report is that, in the face of a joint replacement surgery of the knee, pseudotumor formation is a more likely diagnosis than a neoplastic process when encountering an expanding bony mass. Thus, a biopsy prior to en bloc resection, would be our recommended course of action any time a suspicious mass is encountered close to a TKA. PMID- 29785393 TI - Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography. AB - Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE). TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively) in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD). As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent Australasian position statement recommends that TE should be considered as a routine investigation for monitoring methotrexate therapy, repeated every 3 years if kPa <7.5 and yearly if kPa >7.5. Liver biopsy should be considered for patients with a kPa >9.5. PMID- 29785395 TI - The Relationship between NAFLD and Sarcopenia in Elderly Patients. AB - Aim: Previous studies have shown that individuals with low muscle mass exhibit an increased risk of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the association between NAFLD and sarcopenia in elderly patients. Methods: We classified the participants into sarcopenia/nonsarcopenia groups based on dual-energy X-ray absorptiometry (DXA), muscle strength (grip strength), or/and physical performance (6 m usual gait speed). We diagnosed NAFLD by ultrasonography combined with the history of alcohol intake. Logistic regression analysis was used to assess the correlation between sarcopenia and NAFLD. Results: NAFLD was significantly less frequent in the sarcopenia group than in the nonsarcopenia group (P < 0.01). However, NAFLD was neither an independent risk factor nor a protective factor for sarcopenia. Conclusions: NAFLD is not independently associated with sarcopenia. PMID- 29785394 TI - Notch Signaling Pathway Is Inhibited in the Development of Barrett's Esophagus: An In Vivo and In Vitro Study. AB - Objective: To explore the role of Notch signaling in the development of Barrett's esophagus. Methods: Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results: Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions: Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barrett's esophagus. PMID- 29785396 TI - Expression Characterization of Six Genes Possibly Involved in Gonad Development for Stellate Sturgeon Individuals (Acipenser stellatus, Pallas 1771). AB - Nowadays, in sturgeon's aquaculture, there is a necessity for sex identification at early stages in order to increase the efficiency of this commercial activity. The basis for a correct identification is studying the different factors that influence the gonad development. The research has been directed towards molecular methods that have been employed with various degrees of success in identifying genes with different expression patterns between male and female sturgeons during their development stages. For the purpose of understanding the sexual development of 4-year-old stellate sturgeon (Acipenser stellatus) individuals, we have selected six genes (foxl2, cyp17a1, ar, dmrt1, sox9, and star). We analysed the gene expression of the selected genes for gonads, anal fin, liver, body kidney, and white muscle. The cyp17a1, ar, dmrt1, and sox9 genes have a significant higher expression in male gonads than in female gonads, while the data shows no significant differences in the expression of the investigated genes in the other organs. We investigate these genes to shed light on aquaculture sturgeon sexual development. PMID- 29785397 TI - Whole Genome Sequencing of Greater Amberjack (Seriola dumerili) for SNP Identification on Aligned Scaffolds and Genome Structural Variation Analysis Using Parallel Resequencing. AB - Greater amberjack (Seriola dumerili) is distributed in tropical and temperate waters worldwide and is an important aquaculture fish. We carried out de novo sequencing of the greater amberjack genome to construct a reference genome sequence to identify single nucleotide polymorphisms (SNPs) for breeding amberjack by marker-assisted or gene-assisted selection as well as to identify functional genes for biological traits. We obtained 200 times coverage and constructed a high-quality genome assembly using next generation sequencing technology. The assembled sequences were aligned onto a yellowtail (Seriola quinqueradiata) radiation hybrid (RH) physical map by sequence homology. A total of 215 of the longest amberjack sequences, with a total length of 622.8 Mbp (92% of the total length of the genome scaffolds), were lined up on the yellowtail RH map. We resequenced the whole genomes of 20 greater amberjacks and mapped the resulting sequences onto the reference genome sequence. About 186,000 nonredundant SNPs were successfully ordered on the reference genome. Further, we found differences in the genome structural variations between two greater amberjack populations using BreakDancer. We also analyzed the greater amberjack transcriptome and mapped the annotated sequences onto the reference genome sequence. PMID- 29785398 TI - Marker-Assisted Introgression of Saltol QTL Enhances Seedling Stage Salt Tolerance in the Rice Variety "Pusa Basmati 1". AB - Marker-assisted selection is an unequivocal translational research tool for crop improvement in the genomics era. Pusa Basmati 1 (PB1) is an elite Indian Basmati rice cultivar sensitive to salinity. Here, we report enhanced seedling stage salt tolerance in improved PB1 genotypes developed through marker-assisted transfer of a major QTL, Saltol. A highly salt tolerant line, FL478, was used as the Saltol donor. Parental polymorphism survey using 456 microsatellite (SSR)/QTL-linked markers revealed 14.3% polymorphism between PB1 and FL478. Foreground selection was carried out using three Saltol-linked polymorphic SSR markers RM8094, RM493, and RM10793 and background selection by 62 genome-wide polymorphic SSR markers. In every backcross generation, foreground selection was restricted to the triple heterozygotes of foreground markers, which was followed by phenotypic and background selections. Twenty-four near isogenic lines (NILs), with recurrent parent genome recovery of 96.0-98.4%, were selected after two backcrosses followed by three selfing generations. NILs exhibited agronomic traits similar to those of PB1 and additional improvement in the seedling stage salt tolerance. They are being tested for per se performance under salt-affected locations for release as commercial varieties. These NILs appear promising for enhancing rice production in salinity-affected pockets of Basmati Geographical Indication (GI) areas of India. PMID- 29785399 TI - Timing of Exercise Affects Glycemic Control in Type 2 Diabetes Patients Treated with Metformin. AB - Objective: The purpose of the study was to examine the acute effects of the timing of exercise on the glycemic control during and after exercise in T2D. Methods: This study included 26 T2D patients (14 women and 12 men) who were treated with metformin. All patients were tested on four occasions: metformin administration alone (Metf), high-intensity interval training (HIIT) performed at 30 minutes (EX30), 60 minutes (EX60), and 90 minutes (EX90) postbreakfast, respectively. Glucose, insulin, and superoxide dismutase (SOD) activity were examined. Results: Glucose decreased significantly after the exercise in EX30, EX60, and EX90. Compared with Metf, the decline in glucose immediately after the exercise was larger in EX30 (-2.58 mmol/L; 95% CI, -3.36 to -1.79 mmol/L; p < 0.001), EX60 (-2.13 mmol/L; 95% CI, -2.91 to -1.34 mmol/L; p < 0.001), and EX90 ( 1.87 mmol/L; 95% CI, -2.65 to -1.08 mmol/L; p < 0.001), respectively. Compared with Metf, the decrease in insulin was larger in EX30 and EX60 (both p < 0.001). Conclusions: Timing of exercise is a factor to consider when prescribing exercise for T2D patients treated with metformin. This trial is registered with ChiCTR-IOR 16008469 on 13 May 2016. PMID- 29785401 TI - Rheumatoid Arthritis and miRNAs: A Critical Review through a Functional View. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction associated with an inflammatory environment. The etiology behind RA remains to be elucidated; most updated concepts include the participation of environmental, proteomic, epigenetic, and genetic factors. Epigenetic is considered the missing link to explain genetic diversification among RA patients. Within epigenetic factors participating in RA, miRNAs are defined as small noncoding molecules with a length of approximately 22 nucleotides, capable of gene expression modulation, either negatively through inhibition of translation and degradation of the mRNA or positively through increasing the translation rate. Over the last decade and due to the feasibility of the identification of miRNAs among different tissues and compartments, they have been proposed as biomarkers for diagnosis, prognosis, and response to treatment in different pathologies. Nevertheless, miRNAs seem to be important regulators of networks instead of single genes; their hypothetical use as biomarkers needs to rely on a functional integrative description of their effects in the biological process of autoimmune conditions which until now is missing. Therefore, we underwent a bibliographic search for review and original articles related to miRNAs and their possible implications in rheumatoid arthritis. We found 48 different studies using the key words "miRNAs" or "micro-RNAs" and "rheumatoid arthritis" with restriction of publication dates from 2011 to 2016, in humans, using the English language. After a critical reading, we provide in this paper a functional view with respect to miRNA biogenesis, interaction with targets that are expressed in specific cells and tissues, during different stages of inflammatory responses associated with RA, and recognized specific areas where miRNAs might also have a pathogenic role but remain undescribed. Our results will be useful in designing future research projects that can support miRNAs as biomarkers or therapeutic targets in RA. PMID- 29785400 TI - Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats. AB - The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF-kappaB/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF-kappaB (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats. PMID- 29785402 TI - Formyl Met-Leu-Phe-Stimulated FPR1 Phosphorylation in Plate-Adherent Human Neutrophils: Enhanced Proteolysis but Lack of Inhibition by Platelet-Activating Factor. AB - N-formyl-Met-Leu-Phe (fMLF) is a model PAMP/DAMP driving human PMN to sites of injury/infection utilizing the GPCR, FPR1. We examined a microtiter plate format for measurement of FPR1 phosphorylation in adherent PMN at high densities and found that a new phosphosensitive FPR1 fragment, 25K-FPR1, accumulates in SDS PAGE extracts. 25K-FPR1 is fully inhibited by diisopropylfluorophosphate PMN pretreatment but is not physiologic, as its formation failed to be significantly perturbed by ATP depletion, time and temperature of adherence, or adherence mechanism. 25K-FPR1 was minimized by extracting fMLF-exposed PMN in lithium dodecylsulfate at 4 degrees C prior to reduction/alkylation. After exposure of adherent PMN to a 5 log range of PAF before or after fMLF, unlike in suspension PMN, no inhibition of fMLF-induced FPR1 phosphorylation was observed. However, PAF induced the release of 40% of PMN lactate dehydrogenase, implying significant cell lysis. We infer that PAF-induced inhibition of fMLF-dependent FPR1 phosphorylation observed in suspension PMN does not occur in the unlysed adherent PMN. We speculate that although the conditions of the assay may induce PAF stimulated necrosis, the cell densities on the plates may approach levels observed in inflamed tissues and provide for an explanation of PAF's divergent effects on FPR1 phosphorylation as well as PMN function. PMID- 29785403 TI - Immunotherapy for Hepatocellular Carcinoma: Current Advances and Future Expectations. AB - Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances. PMID- 29785405 TI - Prevalence and Consequences of Injuries in Powerlifting: A Cross-sectional Study. AB - Background: Powerlifting consists of the squat, bench press, and dead lift, and extreme loads are lifted during training and competitions. Previous studies, which have defined an injury as an event that causes an interruption in training or competitions, have reported a relatively low frequency of powerlifting injuries (1.0-4.4 injuries/1000 hours of training). No previous study has investigated the prevalence of injuries, defined as a condition of pain or impairment of bodily function that affects powerlifters' training, in a balanced sample of men and women, and no studies have established possible risk factors for an injury. Purpose: To investigate the prevalence, localization, and characterization of injuries among Swedish subelite classic powerlifters, with an emphasis on differences between men and women, and to investigate whether training and lifestyle factors are associated with an injury. Study Design: Cross sectional study; Level of evidence, 3. Methods: A total of 53 female and 51 male Swedish subelite powerlifters answered an online questionnaire including questions about background characteristics, training habits, and lifestyle factors. The main part of the questionnaire included questions about injuries and their consequences. An injury was defined as a condition of pain or impairment of bodily function that affects powerlifters' training. Results: Seventy percent (73/104) of participants were currently injured, and 87% (83/95) had experienced an injury within the past 12 months. The lumbopelvic region, shoulder, and hip were the most commonly injured areas for both sexes. Women experienced a significantly greater frequency of injuries in the neck and thoracic region than men. Injuries seemed to occur during training, although only 16% (11/70) of those currently injured had to completely refrain from training. Training frequency, greater personal best in the dead lift, injury onset during bench-press and dead lift training, use of straps, alcohol consumption, and dietary issues were associated with current injuries. Conclusion: Injuries are very common in subelite powerlifters. Men and women report similar injury frequencies but different anatomic locations. These injuries do not prevent powerlifters from training and competing, but they may change the content of training sessions. Why powerlifters develop injuries is still unclear; however, it is likely that the management of training loads and optimization of the lifting technique during the squat, bench press, and dead lift are of importance. PMID- 29785404 TI - Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions. AB - Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs), indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF-beta and IL-10 concentrations and measured expression of FOXP3, CTLA-4, CD28, and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system. TGF-beta and IL-10 concentrations were measured using human TGF-beta1 and IL-10 ELISA kit. Relative mRNA expression of studied genes was analyzed by real-time PCR. The frequency of Tregs was significantly higher in MPEs compared to benign effusions; however, the level of TGF-beta and IL-10 in analyzed groups was comparable, and no correlation between concentrations of TGF-beta and IL-10 and percentage of Tregs was observed. Relative mRNA expression of all the genes was higher in CD4+CD25+ compared to CD4+CD25- cells. In CD4+CD25+ cells from MPEs, relative mRNA expression of FOXP3, CTLA-4, and CD28 genes was significantly higher than in benign effusions; however, the level of CD4+CD25+CTLA-4+ cells in analyzed groups showed no significant differences. We found numerous genes correlations in an entire CD4+CD25+ cell subset and CD4+CD25+ cells from MPEs. Enhanced suppressive activity of Tregs is observed in the microenvironment of MPEs. Understanding of relations between cellular and cytokine immunosuppressive factors in tumor microenvironment may determine success of anticancer response. PMID- 29785407 TI - Unusual occurrence of orbital hemangiopericytoma in the zygomatic bone of an adolescent: a case report. AB - Background: Hemangiopericytoma and solitary fibrous tumor are considered related variants on the same spectrum and both may essentially be the same tumor. They are infrequently encountered in the orbital region while the zygomatic bone is an extremely rare location for these neoplasms to occur. Case presentation: A 14 year-old boy presented with complaint of deformity of left infraorbital area and a firm, regular mass in the region. Orbital CT scan revealed a well-defined round isodense intraosseous lesion in the lowermost portion of the lateral orbital wall (zygomatic bone), expanding the bone and protruding anteriorly and medially. MRI showed the mass to be heterogenous and strongly enhancing with contrast medium. Inferior transconjunctival orbitotomy was performed and the mass was removed. The histopathologic examination and immunohistochemistry staining results (positive for CD34, CD31 and smooth muscle actin, but negative for CD99, S100, B-cell lymphoma 2 (bcl-2) and desmin) confirmed the diagnosis of hemangiopericytoma. The postoperative course was uneventful, with no evidence of recurrence after 5 years follow up. Conclusions: This case represents the second hemangiopericytoma reported in the zygomatic bone. Although extremely rare, hemangiopericytoma/solitary fibrous tumor might be considered in the differential diagnosis of intraosseous lesions of the orbital and zygomatic region. PMID- 29785406 TI - Fluid Extravasation in Shoulder Arthroscopic Surgery: A Systematic Review. AB - Background: Arthroscopic surgery of the shoulder joint has become increasingly more common given its advantages over open surgery; however, one rare but potentially life-threatening complication is fluid extravasation into the surrounding tissues, causing edema, respiratory compromise, abnormal results on laboratory blood tests, and possibly death. Currently, no systematic review exists that summarizes the existing clinical research on this topic. Purpose: To perform a systematic review on fluid extravasation as a complication of shoulder arthroscopic surgery, specifically assessing clinical presentation, risk factors, management, and outcomes. Study Design: Systematic review; Level of evidence, 4. Methods: Two reviewers independently searched 3 databases (PubMed, Ovid [MEDLINE], and Embase) from database inception until July 1, 2017. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist guided the reporting and data abstraction. The methodological quality of these studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The results are presented in a narrative summary fashion using descriptive statistics including ranges and agreement statistics. Results: A total of 26 studies (20 case reports, 4 case series, and 2 prospective comparative studies) encompassing 205 patients (mean age, 50.8 years [range, 15 83 years]) were included. The most common signs of fluid extravasation included chest wall swelling (n = 86) and neck swelling (n = 116). In 32 patients, observation alone was sufficient. Other patients required airway intubation (n = 16), diuretics (n = 7), steroids (n = 1), and percutaneous drainage of fluid (n = 1). Clinical edema resolved after 2 to 48 hours, and patients were discharged 1 to 20 days postoperatively. Serious complications included transfer to the intensive care unit (n = 14), anterior interosseous nerve palsy (n = 4), rhabdomyolysis (n = 1), and death (n = 1). Conclusion: Fluid extravasation has the potential to be a life-threatening complication of shoulder arthroscopic surgery; however, it is most commonly managed nonoperatively, and symptoms typically resolve with no evidence of long-term complications. Intraoperative surgical decisions, such as minimizing the surgical time and volume of irrigation fluid used, may limit fluid extravasation, while careful intraoperative monitoring may facilitate prompt diagnosis and management to optimize patient outcomes. PMID- 29785409 TI - De novo genome and transcriptome resources of the Adzuki bean borer Ostrinia scapulalis (Lepidoptera: Crambidae). AB - We present a draft genome assembly with a de novo prediction and automated functional annotation of coding genes, and a reference transcriptome of the Adzuki bean borer, Ostrinia scapulalis, based on RNA sequencing of various tissues and developmental stages. The genome assembly spans 419 Mb, has a GC content of 37.4% and includes 26,120 predicted coding genes. The reference transcriptome holds 33,080 unigenes and contains a high proportion of a set of genes conserved in eukaryotes and arthropods, used as quality assessment of the reconstructed transcripts. The new genomic and transcriptomic data presented here significantly enrich the public sequence databases for the Crambidae and Lepidoptera, and represent useful resources for future researches related to the evolution and the adaptation of phytophagous moths. The genome and transcriptome assemblies have been deposited and made accessible via a NCBI BioProject (id PRJNA390510) and the LepidoDB database (http://bipaa.genouest.org/sp/ostrinia_scapulalis/). PMID- 29785408 TI - Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis. AB - Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions. PMID- 29785410 TI - Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis. AB - Objective: Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). Methods: In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. Results: A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA. PMID- 29785411 TI - Low-Dose CT Perfusion of the Liver using Reconstruction of Difference. AB - Liver CT perfusion (CTP) is used in the detection, staging, and treatment response analysis of hepatic diseases. Unfortunately, CTP radiation exposures is significant, limiting more widespread use. Traditional CTP data processing reconstructs individual temporal samples, ignoring a large amount of shared anatomical information between temporal samples, suggesting opportunities for improved data processing. We adopt a prior-image-based reconstruction approach called Reconstruction of Difference (RoD) to enable low-exposure CTP acquisition. RoD differs from many algorithms by directly estimating the attenuation changes between the current patient state and a prior CT volume. We propose to use a high fidelity unenhanced baseline CT image to integrate prior anatomical knowledge into subsequent data reconstructions. Using simulation studies based on a 4D digital anthropomorphic phantom with realistic time-attenuation curves, we compare RoD with conventional filtered-backprojection, penalized-likelihood estimation, and prior image penalized-likelihood estimation. We evaluate each method in comparisons of reconstructions at individual time points, accuracy of estimated time-attenuation curves, and in an analysis of common perfusion metric maps including hepatic arterial perfusion, hepatic portal perfusion, perfusion index, and time-to-peak. Results suggest that RoD enables significant exposure reductions, outperforming standard and more sophisticated model-based reconstruction, making RoD a potentially important tool to enable low-dose liver CTP. PMID- 29785412 TI - Horizontal lateral lamella as a risk factor for iatrogenic cerebrospinal fluid leak. Clinical retrospective evaluation of 24 cases. AB - BACKGROUND: Several authors highlighted the limitations of the Keros classification system in predicting intracranial entry risk. Recently, our group proposed a new classification system based on the angle formed between the lateral lamella of the cribriform plate (LLCP) and the continuation of an horizontal plane passing through the cribriform plate (Gera classification). The aim of this study was to analyze whether the risk of iatrogenic cerebrospinal fluid leak (CSF-L) was better predicted by Keros or Gera classification. METHODOLOGY: The pre-operative CT scans of 24 patients (CSF-L group) who suffered from iatrogenic CSF-L during endoscopic sinus surgery (ESS) were compared to those obtained from a group of 100 patients who underwent uneventful ESS (control group). The skull base measurements as well as the distribution of Keros and Gera classes in the 2 groups were analyzed. RESULTS: No difference in the distribution of Keros classes or in the depth of the cribriform plate between CSF-L and control group were demonstrated. On the contrary, significant differences in the distribution of Gera classes and in the degree of the angle formed by the LLCP and the continuation of the horizontal plane passing through the cribriform plate were found. In particular, according to Gera classification system, 19 out of 24 patients in the CSF-L group were considered at risk for iatrogenic CSF-L. CONCLUSIONS: Gera classification system might be more sensitive to anatomical variations associated with CSF-L than the Keros one, further suggesting the application of the former during the preoperative CT scan evaluation. PMID- 29785413 TI - Multivariate analysis of inflammatory endotypes in recurrent nasal polyposis in a Chinese population. AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical problem due to its propensity for recurrence. However, data on the frequency of CRSwNP recurrence after surgery in China are rare. METHODS: 78 CRSwNP patients undergoing functional endoscopic sinus surgery were followed up for 8 years and classified into recurrent and non-recurrent groups. A cluster analysis of the CRSwNP based on inflammatory endotypes was performed, and the endotypes were secondarily matched with clinical phenotypes. RESULTS: The recurrence rate of CRSwNP in Southwest China was 21.8% over 8 years post-surgery. The CRSwNP was classified into 4 clusters: cluster 1 (higher expression of IL-5, IgE, and ECP and high positivity rate for SE-IgE); cluster 2 (higher concentrations of IL-6, IL-8 and MPO); cluster 3 (higher concentrations of TNF alpha; and IFN-gamma); and cluster 4 (higher expression of IL-17). Cluster 1 (type-2 inflammation) exhibited the highest recurrence rate, co-morbid asthma and atopy. Notably, the ECP/MPO ratio increased significantly in patients with non type-2 recurrent CRSwNP 8 years after the first surgery. CONCLUSION: Different inflammatory endotypes of CRSwNP exhibited clearly different prognoses. The type 2 subgroup had high recurrence and co-morbid asthma rates comparable to the rates reported in Western countries. PMID- 29785414 TI - Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours. AB - BACKGROUND: Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. METHODOLOGY: The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. RESULTS: A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. CONCLUSIONS: This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose. PMID- 29785418 TI - Regioselective ortho-functionalization of bromofluorenecarbaldehydes using TMPMgCl.LiCl. AB - A highly regioselective functionalization of 7-bromofluorene-2-carbaldehydes, potent organic chromophores, in position C3 using a mild ortho-metallation strategy (DoM) with TMPMgCl.LiCl has been developed. This approach allows the preparation of highly functionalized fluorene derivatives by conversion of the in situ generated metalated species with various electrophiles giving a fast access to novel organic phosphorescent dyes. PMID- 29785421 TI - In situ identification of cation-exchange-induced reversible transformations of 3D and 2D perovskites. AB - The optical and structural properties of hybrid perovskites can be tuned by the post-synthetic introduction of new cations. To advance the development of this approach, knowledge of the reaction mechanism is essential, but has not yet been elucidated. Here, the effect of n-octylamine on three-dimensional (3D) methylammonium lead bromide (MAPbBr3) was investigated by in situ X-ray photoelectron spectroscopy. Spectroscopic analysis indicated equimolar substitutions between octylammonium (OcA+) and methylammonium (MA+) cations that cause the formation of two-dimensional (2D) octylammonium lead bromide ((OcA)2PbBr4). The introduction of methylamine reversed these changes, and the cation exchange between MA+ and OcA+ caused the reverse conversion to MAPbBr3. PMID- 29785419 TI - Tuning the electrochemical potential of perfunctionalized dodecaborate clusters through vertex differentiation. AB - We report a new class of redox-active vertex-differentiated dodecaborate clusters featuring pentafluoroaryl groups. These [B12(OR)11NO2] clusters share several unique photophysical properties with their [B12(OR)12] analogues, while exhibiting significantly higher (+0.5 V) redox potentials. This work describes the synthesis, characterization, and isolation of [B12(O-CH2C6F5)11NO2] clusters in all 3 oxidation states (dianion, radical, and neutral). Reactivity to post functionalization with thiol species via SNAr on the pentafluoroaryl groups is also demonstrated. PMID- 29785422 TI - Super-resolution force spectroscopy reveals ribosomal motion at sub-nucleotide steps. AB - Probing biomolecular motion beyond a single nucleotide is technically challenging but fundamentally significant. We have developed super-resolution force spectroscopy (SURFS) with 0.5 pN force resolution and revealed that the ribosome moves by half a nucleotide upon the formation of the pre-translocation complex, which is beyond the resolution of other techniques. PMID- 29785423 TI - Targeted replacement: systematic studies of dodecanuclear {MLn} coordination clusters (M = Cr, Co; Ln = Dy, Y). AB - Three dodecanuclear 3d-4f coordination clusters, [CrIII6LnIII6(MU3 OH)8(tbdea)6(C6H5COO)16].2H2O (Ln = Dy (1), Y (2)) and [CoIII6DyIII6(MU3 OH)8(nbdea)6(m-CH3C6H4COO)16].2H2O.2CH3CN (3), have been synthesized under solvothermal conditions and characterized. Single-crystal X-ray diffraction analysis revealed that all three compounds possess an analogous {MIII6LnIII6} core (M = Cr, Co; Ln = Dy, Y) and dc magnetic susceptibility studies indicated that the magnetic exchange couplings between DyIII ions are dominant antiferromagnetic, while the CrIII-DyIII interactions are weakly ferromagnetic. Furthermore, the ac magnetic susceptibility measurements showed that both CrIII6DyIII6 compound 1 and CoIIi6DyIII6 compound 3 containing highly anisotropic DyIII ions displayed single-molecule magnetic (SMM) behavior with the energy barrier Ueff increasing from 12.8 K (for 1) to 20.8 K (for 3), indicating that weak 3d-4f exchange couplings enhance the QTM and reduce the energy barrier. PMID- 29785426 TI - Theoretical insights into the reactivity of Fe-based catalysts for water oxidation: the role of electron-withdrawing groups. AB - Recent experiments have shown that complex (1), [Fe(OTf)2(Pytacn)] (OTf = CF3SO3 , Pytacn = 1-(2'-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane), is a promising artificial photosynthetic catalyst because of its distinct capability in water oxidation. Experimentalists have also synthesized several derivatives, e.g., [Fe(OTf)2(E,HPytacn)] (E = -Cl (2), -CO2Et (3) and -NO2 (4)) and [Fe(OTf)2 (E,RPytacn)] (R = -F (5) and R = -Me (6)), and proposed that the E-substituted electron-withdrawing groups could improve the catalytic efficiency. However, the mechanism remains somewhat unclear, especially on the relative catalytic efficiency of these complexes. In this work, we propose an oxygen radical mechanism based on density functional theory (DFT) calculations for the six complexes. The crucial O-O bond-formation step is elucidated. Our calculations reveal that the FeIV-oxyl radical is the active species during the reaction, and the catalytic activities follow the sequence of (4) > (3) > (2) > (1) > (5) > (6), which agrees consistently with the experimental findings. Furthermore, we propose a simple charge-pair interaction model to characterize the effect of electron-withdrawing groups on the catalytic efficiency. It is clearly demonstrated that an electron-withdrawing group with a higher electronegativity is associated with a lower Gibbs free energy barrier for the O-O bond formation, which then leads to a more active catalyst. We also emphasize that the accurate description of dispersive interactions in DFT calculations is crucially important to retrieve the correct sequence of the catalytic efficiency. The theoretical insights provided in this work could be useful for the design of highly efficient Fe-based water oxidation catalysts. PMID- 29785424 TI - Iron nanoparticles in capsules: derived from mesoporous silica-protected Prussian blue microcubes for efficient selenium removal. AB - A spatially confined reduction strategy for the fabrication of small nanoparticles in a micro-box is reported, where iron nanoparticles with uniform diameter are highly distributed in a carbon matrix and surrounded by a mesoporous silica layer. Due to their unique confined nanostructure, the Fe/C@mSiO2 capsules could effectively remove and recycle Se(iv) from a low concentration solution. PMID- 29785428 TI - 1-Methyl-4-aryl-urazole (MAUra) labels tyrosine in proximity to ruthenium photocatalysts. AB - We designed and synthesised peptides conjugated with proline linkers and ruthenium photocatalysts. These peptides were used as substrates to evaluate the photocatalyst-proximity dependences of candidates for tyrosine labelling reagents. The 1-methyl-4-aryl-urazole (MAUra) structure was found to be a novel tyrosyl radical trapping agent to label tyrosine residues effectively under the conditions where the ruthenium photocatalyst and tyrosine were in close proximity. Using a ruthenium photocatalyst conjugated to a carbonic anhydrase ligand, the target protein in a complex protein mixture was labelled with remarkable target selectivity by azide- or desthiobiotin-conjugated MAUra derivatives. PMID- 29785429 TI - Bimodal coordination of fused arenes to a Pd3 cluster site. AB - We report bimodal coordination behaviour of fused arenes at a Pd3 cluster site. A cyclooctatetraene-supported Pd3 cluster accommodates anthracene and tetracene in an oxidative pi-addition manner, whereas triphenylene and fluoranthene are accommodated in a pi-coordination manner. PMID- 29785430 TI - Staudinger reaction using 2,6-dichlorophenyl azide derivatives for robust aza ylide formation applicable to bioconjugation in living cells. AB - Efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6 dichlorophenyl azide and triarylphosphines. The reaction proceeds rapidly and has been successfully applied to chemical modification of proteins in living cells. PMID- 29785431 TI - Slow magnetic relaxation and luminescence properties in lanthanide(iii)/anil complexes. AB - The initial use of anils, i.e. bidentate Schiff bases derived from the condensation of anilines with salicylaldehyde or its derivatives, in 4f-metal chemistry is described. The 1 : 1 reactions between Ln(NO3)3.xH2O (Ln = lanthanide) or Y(NO3)3.6H2O and N-(5-bromosalicylidene)aniline (5BrsalanH) in MeCN has provided access to complexes [Ln(NO3)3(5BrsalanH)2(H2O)].MeCN (Ln = Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb) and [Y(NO3)3(5BrsalanH)2(H2O)].MeCN, respectively, in good yields. The structures of the isomorphous complexes with Ln = Pr(1.MeCN), Sm(3.MeCN), Gd(5.MeCN), Dy(7.MeCN) and Er(9.MeCN) have been determined by single-crystal X-ray crystallography. The other complexes were proven to be isostructural with the fully structurally characterized compounds based on elemental analyses, IR spectra, unit cell determinations and powder X ray patterns. The 9-coordinate LnIII centre in the [Ln(NO3)3(5BrsalanH)2(H2O)] molecules is bound to six oxygen atoms from the three bidentate chelating nitrato groups, two oxygen atoms that belong to the organic ligands and one oxygen atom from the aquo ligand. The 5BrsalanH molecules behave as monodentate O-donors; the acidic H atom is clearly located on the imino N atom and thus the formally neutral ligands adopt an extremely rare coordination mode participating in the zwitterionic form. The coordination polyhedra defined by the nine donor atoms around the LnIII centres are best described as spherical capped square antiprisms. Various intermolecular interactions build the crystal structures and Hirshfeld surface analysis was applied to evaluate the magnitude of interactions between the molecules. Solid-state IR and UV/VIS data are discussed in terms of structural features. 1H NMR data prove that the diamagnetic [Y(NO3)3(5BrsalanH)2(H2O)] complex decomposes in DMSO. Combined dc and ac magnetic susceptibility, as well as magnetization data for 7 suggest that this complex shows field-induced slow magnetic relaxation. Two magnetization relaxation processes are evident. The fit to the Arrhenius law has been performed using the 6.5-8.5 K ac data, affording an effective barrier for the magnetization reversal of 27 cm-1. Cole-Cole plot analysis in the temperature range in which the Orbach relaxation process is assumed, reveals a narrow distribution of relaxation times. The solid Dy(iii) complex 7 emits green light at 338 nm, the emission being ligand-centered. The perspectives of the present, first results in the lanthanide(iii)-anil chemistry are critically discussed. PMID- 29785432 TI - Molecular insights into avibactam mediated class C beta-lactamase inhibition: competition between reverse acylation and hydrolysis through desulfation. AB - Avibactam is one of the promising next generation beta-lactamase inhibitors due to its exceptional inhibition against wide-spectrum serine beta-lactamases. The unusual reversible acylation mechanism has particularly gained interest to explain the inhibition mechanism of avibactam. We explore the mechanism of acylation and deacylation involving avibactam in class-C beta-lactamases (CBLs) through hybrid quantum mechanical/molecular mechanical (QM/MM) enhanced sampling molecular dynamics (MD) simulations. Based on these computations, we probe the kinetic stability of the acyl-enzyme complex formed by avibactam and CBLs, thereby gaining molecular level insights into the avibactam-mediated inhibition of CBLs. PMID- 29785433 TI - The immunomodulatory activity and mechanism of docosahexenoic acid (DHA) on immunosuppressive mice models. AB - In this study, the immunomodulatory activity of docosahexaenoic acid (DHA) on the immunosuppressive BALB/c mice model and its molecular mechanism are elucidated. It was found that the weight indexes of the spleen and thymus were significantly increased by DHA (44.0 mg kg-1 and 88.0 mg kg-1) treatment in the prevention or cure groups. The result of macrophages showed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could promote the proliferation and phagocytosis activity of macrophages in the prevention or cure groups. In addition, DHA could activate macrophages by the G-protein coupled cell membrane receptor GPR120- Mitogen-Activated Protein Kinases (MAPKs)-nuclear factor kappaB (NF-kappaB) p65 pathway in vivo. The result of the spleen showed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could promote the proliferation of spleen cells and the natural killer (NK) cells activity in vivo. In the prevention or cure groups, the quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could enhance the production of cytokines IL-1beta, IL-2, TNF-alpha and IFN-gamma in the spleen of immunosuppressive mice. The HE (hematoxylin and eosin) stained histopathological images showed that DHA could repair the damage induced by CTX in the spleen cells of the prevention or cure groups. These results suggested that DHA has a remarkable immunomodulatory activity on the immunosuppressive mice model in the prevention or cure groups. PMID- 29785435 TI - Assessing the performance of MM/PBSA and MM/GBSA methods. 7. Entropy effects on the performance of end-point binding free energy calculation approaches. AB - Entropy effects play an important role in drug-target interactions, but the entropic contribution to ligand-binding affinity is often neglected by end-point binding free energy calculation methods, such as MM/GBSA and MM/PBSA, due to the expensive computational cost of normal mode analysis (NMA). Here, we systematically investigated entropy effects on the prediction power of MM/GBSA and MM/PBSA using >1500 protein-ligand systems and six representative AMBER force fields. Two computationally efficient methods, including NMA based on truncated structures and the interaction entropy approach, were used to estimate the entropic contributions to ligand-target binding free energies. In terms of the overall accuracy, we found that, for the minimized structures, in most cases the inclusion of the conformational entropies predicted by truncated NMA (enthalpynmode_min_9A) compromises the overall accuracy of MM/GBSA and MM/PBSA compared with the enthalpies calculated based on the minimized structures (enthalpymin). However, for the MD trajectories, the binding free energies can be improved by the inclusion of the conformation entropies predicted by either truncated-NMA for a relatively high dielectric constant (epsilonin = 4) or the interaction entropy method for epsilonin = 1-4. In terms of reproducing the absolute binding free energies, the binding free energies estimated by including the truncated-NMA entropies based on the MD trajectories (DeltaGnmode_md_9A) give the lowest average absolute deviations against the experimental data among all the tested strategies for both MM/GBSA and MM/PBSA. Although the inclusion of the truncated NMA based on the MD trajectories (DeltaGnmode_md_9A) for a relatively high dielectric constant gave the overall best result and the lowest average absolute deviations against the experimental data (for the ff03 force field), it needs too much computational time. Alternatively, considering that the interaction entropy method does not incur any additional computational cost and can give comparable (at high dielectric constant, epsilonin = 4) or even better (at low dielectric constant, epsilonin = 1-2) results than the truncated-NMA entropy (DeltaGnmode_md_9A), the interaction entropy approach is recommended to estimate the entropic component for MM/GBSA and MM/PBSA based on MD trajectories, especially for a diverse dataset. Furthermore, we compared the predictions of MM/GBSA with six different AMBER force fields. The results show that the ff03 force field (ff03 for proteins and gaff with AM1-BCC charges for ligands) performs the best, but the predictions given by the tested force fields are comparable, implying that the MM/GBSA predictions are not very sensitive to force fields. PMID- 29785434 TI - Integration of phospholipid-hyaluronic acid-methotrexate nanocarrier assembly and amphiphilic drug-drug conjugate for synergistic targeted delivery and combinational tumor therapy. AB - Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery. The HCPT-MTX conjugate was synthesized by a blood-stable yet intracellularly hydrolysable ester bond. The core-shell-corona DSPE-HA-MTX nanoparticles encapsulating HCPT-MTX (HCPT-MTX@DHM) exhibited high drug entrapment efficiency (~91.8%) and pH/esterase-controlled release behavior. Cellular uptake studies confirmed significant increase in the efficiency of selective internalization of HCPT-MTX@DHM via CD44/folate receptors compared with those of DSPE-HA nanoparticles encapsulating HCPT-MTX (HCPT MTX@DH), both drugs, or each individual drug. Furthermore, in vivo near-infrared fluorescence and photoacoustic dual-modal imaging indicated that DiR-doped HCPT MTX@DHM nanoparticles efficiently accumulated at the tumor sites through passive plus-active targeting. Finally, the synergistic active targeting and synchronous dual-drug release at a synergistic drug-to-drug ratio resulted in highly synergetic tumor cell-killing and tumor growth inhibition in MCF-7 tumor-bearing mice. Therefore, HCPT-MTX@DHM nanoparticles can be an efficient and smart platform for tumor-targeting therapy. PMID- 29785436 TI - Ru-Complexes of an anionic germabenzenyl ligand. AB - Ruthenium complexes having an anionic germabenzenyl ligand, [Cp*Ru{eta1,eta3 GeC5(t-Bu)H4}]2 (1) and [Cp*Ru{eta1-GeC5(t-Bu)H4}{[eta1,eta5-GeC5(t Bu)H4]RuCp*}2] (2), have been synthesized by the reaction of germabenzenylpotassium, KGeC5(t-Bu)H4, with [Cp*RuCl]4. Complexes 1 and 2 exhibit both sigma- and pi-type coordination and can be regarded as the first examples of a transition-metal substituted benzenoid of heavier Group 14 elements. The isolated complexes 1 and 2 have been characterized using NMR and UV-vis spectroscopy, X-ray crystallographic analysis, and theoretical calculations. PMID- 29785437 TI - Confinement boosts CO oxidation on an Ni atom embedded inside boron nitride nanotubes. AB - To date, most studies of heterogeneous catalysis have focused on metal particles supported on the surface of substrates. However, studies of the catalytic properties of metallic nanoparticles supported on the interior surface of nanotubes are rare. Using first-principles calculations based on density functional theory, we have studied the CO oxidation on a single nickel atom confined in a nitrogen vacancy on the inside surface of boron nitride nanotubes (BNNT). By exploring the Eley-Rideal mechanism, we find that an Ni atom embedded on the interior surface of BNNTs exhibits a much higher catalytic activity for CO oxidation when compared with Ni doped on their outside surface. In addition, the energy barriers of the rate-determining step for CO oxidation on Ni embedded on the inside wall of BNNT(5,5), BNNT(6,6) and BNNT(7,7) are 0.39, 0.29 and 0.33 eV, respectively. The results illustrate the merit of confinement for CO oxidation. PMID- 29785438 TI - Monodisperse and brightly luminescent CsPbBr3/Cs4PbBr6 perovskite composite nanocrystals. AB - The microscale composite structure strategy of embedding CsPbBr3 nanocrystals (NCs) in the microscale Cs4PbBr6 matrix (CPB113/CPB416) has successfully demonstrated its ability to resolve the fluorescence quenching of perovskite NCs in the solid agglomeration state due to the loss of quantum confinement. Unfortunately, the controllable synthesis of monodisperse nanoscale composites with bright emission in the solid state remains a great challenge. Here, we present for the first time a novel supersaturated recrystallization process to controllably synthesize monodisperse CPB113/CPB416 composite NCs with bright emission in the solid form, where CsPbBr3 NCs were uniformly embedded in the nano hexagonal Cs4PbBr6 matrix. The existence of 2-methylimidazole (MeIm) not only can control the composition rate of CsPbBr3 to Cs4PbBr6, the size and dispersity of CsPbBr3 in the composite NCs but can also help controllably obtain the monodisperse and hexagonal Cs4PbBr6 matrix. The as-prepared composite structure can effectively prevent CsPbBr3 fluorescence quenching and make the composite NCs have a high photoluminescence quantum yield (PLQY) of 83%. In addition, we obtained tunable blue to red emitting composite NCs by varying the halide salts. PMID- 29785440 TI - An immunoconjugated up-conversion nanocomplex for selective imaging and photodynamic therapy against HER2-positive breast cancer. AB - Photodynamic therapy represents a very attractive therapeutic tool considered to be effective, minimally invasive and minimally toxic. However, conventional photodynamic therapy actually has two main constraints: the limited penetration depth of visible light needed for its activation, and the lack of selectivity. Considering this, this work reports the synthesis and evaluation of a novel nanoconjugate for imaging and selective photodynamic therapy against HER2 positive breast cancer, a particularly aggressive form of the disease. It was demonstrated that upon 975 nm near infrared light exposure, the red emission of the NaYF4:Yb,Er up-conversion nanoparticles (UCNPs) can be used for optical imaging and simultaneously represent the source for the excitation of a covalently bound zinc tetracarboxyphenoxy phthalocyanine (ZnPc), a photosensitizer that in turn transfers energy to ground state molecular oxygen to produce cytotoxic singlet oxygen. The specificity of our nanoconjugates was achieved by immunoconjugation with Trastuzumab (Tras), a specific monoclonal antibody for selective detection and treatment of HER2-overexpressing malignant breast cancer cells. Selective tracking of SKBR-3 HER2-positive cells was verified by confocal microscopy analysis, and the photodynamic therapy effect was considerably improved when Trastuzumab was incorporated into the nanoconjugate, the UCNPs-ZnPc-Tras being practically inert in the absence of infrared light exposure but reducing the HER2-positive cell viability up to 21% upon 5 min of the irradiation. This theranostic nanoconjugate represents a valuable alternative for HER2-positive breast cancer imaging and selective photodynamic therapy. PMID- 29785439 TI - Highly efficient upconversion emission of Er3+ in delta-Sc4Zr3O12 and broad-range temperature sensing. AB - Developing optical temperature sensors with a wider range, higher sensitivity and repeatability based on Er3+/Yb3+ doped upconverting phosphors has always been at the forefront of temperature measurement technologies. Here, we report the intense green upconversion luminescence in Er3+/Yb3+ doped delta-Sc4Zr3O12 for the first time and its temperature sensing performance is investigated. The structure of delta-Sc4Zr3O12 is given by Rietveld refinement of XRD data and the site occupancy of Er3+ ions has been determined. Compared with cubic Sc2O3 and ZrO2, under 972 nm excitation, the green emission from Er3+ centers in Sc4Zr3O12 is increased by 59-fold and 264-fold, respectively. By experimental analysis, this enhancement of upconversion luminescence is attributed to the low symmetrical environment of Er3+, generation of Yb3+ clusters and high internal efficiency of Yb3+ emission in Sc4Zr3O12. In addition, the fluorescence intensity ratio of two green emission bands (2H11/2/4S3/2 -> 4I15/2) is studied as a function of temperature ranging from 303 to 793 K in Sc4Zr3O12. The maximum sensitivity observed via calculation is 0.00634 K-1 at 573 K, and the sensitivity is still as high as 0.00534 K-1 at 793 K. The stability of a Sc4Zr3O12 thermometer is also examined via a recycling test. These findings suggest that delta-Sc4Zr3O12 is a promising upconversion host and could achieve high sensitivity optical temperature sensing with a wide measuring range. PMID- 29785441 TI - Processing of PVDF-based electroactive/ferroelectric films: importance of PMMA and cooling rate from the melt state on the crystallization of PVDF beta crystals. AB - Poly(vinylidene difluoride) (PVDF) displays attractive ferroelectric/piezoelectric properties and its polar beta-crystals are specifically targeted for achieving electroactive applications. However, their direct crystallization from the melt state represents a challenging task that has never been addressed using melt-state processes. The use of poly(methyl methacrylate) (PMMA) is herein investigated to promote the PVDF polar beta-phase using melt-blending and extrusion-calendering technologies. The presence of the beta-phase is here confirmed by ATR-FTIR and WAXS experiments with blends at a PMMA content as low as 5 wt%. The key role of PMMA for the beta-phase crystallization from the melt state was unambiguously highlighted with the help of Flash DSC experiments in non-isothermal cooling mode from the melt state. PMMA is able to efficiently shift the alpha-to-beta crystal transition to lower cooling rates (>100-200 degrees C s-1), making the achievement of the PVDF polar beta-phase for these blends compatible with conventional processing tools. A crystal phase diagram is proposed for the PVDF/PMMA blends to highlight the dual effects of both PMMA and cooling rate on the PVDF crystallization during melt processing. Ferroelectric properties were even observed for the blends containing PMMA up to 10 wt% with the highest remanent polarization obtained at 5 wt% PMMA. After 10 wt% PMMA, a progressive transition from ferroelectric to pseudo-linear dielectric behavior is observed more likely due to the presence of PMMA in the interlamellar amorphous phase of the polar PVDF spherulites as shown by SAXS experiments. In this work, we successfully demonstrated that PMMA plays a key role in the crystallization of PVDF polar crystals from the melt state, enabling large-scale and continuous extrusion processing of PVDF-based materials with attractive dielectric properties for sensing and harvesting applications. PMID- 29785442 TI - Photoinduced intramolecular charge transfer in a cross-conjugated push-pull enediyne: implications toward photoreaction. AB - Push-pull organic fluorophores are important owing to their interesting optoelectronical properties. Here we report the photophysics of a new cross conjugated push-pull enediynyl dye which belongs to an unexplored class of pi conjugated donor-acceptor systems. Two N,N-dimethylaniline moieties serve as donors and one pyrene ring functions as an acceptor via a common Y-shaped 'enediyne' bridge which facilitates the cross-electronic communication. The dye exhibits dual emission from locally excited (LE) and intramolecular charge transfer (ICT) states. While the LE emission is dominant in non-polar solvents, the ICT emission predominates in polar solvents. Time-resolved fluorescence decay experiments reveal a relatively shorter lifetime component (~0.5-0.9 ns) belonging to an ICT state and a relatively longer lifetime species (~1.6-2.8 ns) corresponding to the LE state. The strong ICT behavior of the dye is manifested through the huge red-shift (4166 cm-1) of the emission spectra from non-polar cyclohexane to polar N,N-dimethylformamide. In contrast to many small push-pull organic dyes, the LE and ICT states of the push-pull enediynyl dye follow the same excitation pathway. The dominant red-shifted ICT emission (~550 nm) intensity of the dye in polar solvent decreases with a concomitant appearance of the blue-shifted LE emission (~385 nm) upon prolonged exposure to photons. This opens up a new photophysical strategy of achieving high contrast two fluorescence color conversion from yellow to blue. PMID- 29785443 TI - Organic-inorganic hybrid perovskite quantum dots with high PLQY and enhanced carrier mobility through crystallinity control by solvent engineering and solid state ligand exchange. AB - The photoluminescence quantum yield (PLQY) and charge carrier mobility of organic inorganic perovskite QDs were enhanced by the optimization of crystallinity and surface passivation as well as solid-state ligand exchange. The crystallinity of perovskite QDs was determined by the Effective solvent field (Esol) of various solvents for precipitation. The solvent with high Esol could more quickly countervail the localized field generated by the polar solvent, and it causes fast crystallization of the dissolved precursor, which results in poor crystallinity. The post-ligand adding process (PLAP) and post-ligand exchange process (PLEP) increase the PLQY of perovskite QDs by reducing non-radiative recombination and the density of surface defect states through surface passivation. Particularly, the post ligand exchange process (PLEP) in the solid state improved the charge carrier mobility of perovskite QDs in addition to the PLQY enhancement. The ligand exchange with short alkyl chain length ligands could improve the packing density of perovskite QDs in films by reducing the inter particle distance between perovskite QDs. The maximum hole mobility of 6.2 * 10-3 cm2 V-1 s-1, one order higher than that of pristine QDs without the PLEP, is obtained at perovskite QDs with hexyl ligands. By using PLEP treatment, compared to the pristine device, a 2.5 times higher current efficiency in perovskite QD LEDs was achieved due to the improved charge carrier mobility and PLQY. PMID- 29785444 TI - Synthesis of N-alkylated 2-pyridones through Pummerer type reactions of activated sulfoxides and 2-fluoropyridine derivatives. AB - N-Alkylated 2-pyridone products were obtained in good to excellent yields through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride activated sulfoxides and 2-fluoropyridine derivatives, followed by hydrolysis. This is a rare case that uses 2-fluoropyridine as a nucleophile in Pummerer type reactions. PMID- 29785445 TI - Acoustically enhanced photodetection by a black phosphorus-MoS2 van der Waals heterojunction p-n diode. AB - We developed a new way to enhance the photoresponsivity of a van der Waals heterojunction p-n diode using surface acoustic waves (SAWs). The diode was constructed on top of a piezoelectric LiNbO3 substrate and composed of p-type black phosphorus (BP) and n-type molybdenum disulfide (MoS2) flakes that partly overlapped with each other. This layout facilitated the applied SAWs to rapidly drive carriers out of the depletion region. In this structural design, SAWs promoted the separation of photogenerated carriers, and thus greatly increased the photocurrent. The measured photocurrent for the device with SAWs was about 103 times higher than that of the device without SAWs. The device using SAWs showed a photoresponsivity as high as 2.17 A W-1 at the wavelength of 582 nm. This excellent performance was attributed to the SAWs suppressing electron-hole recombination in the device under light illumination. Our device exhibits promise as a high-performance photodetector and reveals new possibilities for acoustic devices in optoelectronics. PMID- 29785447 TI - Posterior cortical breakage leads to posterior tibial slope change in lateral hinge fracture following opening wedge high tibial osteotomy. AB - PURPOSE: This study was designed to analyze the relationship between changes in posterior tibial slope and the absence or presence of lateral hinge fracture, diagnosed in the sagittal and axial planes, as well as the coronal plane, by computed tomography (CT) following opening wedge high tibial osteotomy (HTO). METHODS: This study involved 55 patients (55 knees) undergoing opening wedge HTO for primary medial osteoarthritis. Lateral hinge fractures were evaluated on CT scans according to the Takeuchi classification and were also classified as subtypes A, B, and C, depending on anterior, posterior, and both anterior and posterior cortical disruptions, respectively, as determined by the sagittal and axial planes of CT scans which corresponded to the fracture line visible on coronal CT scans. RESULTS: Of the 55 knees, 23 were found on postoperative CT scans to have lateral hinge fractures. All 23 were classified as Type I, with 11, 12, and 0 being subtypes A, B, and C, respectively. Mean change in posterior tibial slope from 3 weeks postoperatively to last follow up in subtype B was significantly greater than in subtype A (2.5 degrees vs 0.2 degrees , P = 0.008) and in knees without hinge fracture (2.5 degrees vs 0.1 degrees , P = 0.002). CONCLUSION: Type I lateral hinge fractures encroached either the anterior or posterior cortex of the proximal tibia, but not both. In addition, posterior tibial slope increased over time following surgery in knees with Type I lateral hinge fracture and posterior cortex breakage, suggesting that caution should be exercised when deciding the starting time for weight bearing in such patients. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 29785448 TI - Patella alta and patellar subluxation might lead to early failure with inlay patello-femoral joint arthroplasty. AB - PURPOSE: With the growing interest in resurfacing procedures, several new implants have been recently introduced for isolated patello-femoral joint arthroplasty (PFA). However, not much data are available for these new techniques or about the right indications for each type of implant. METHODS: Out of a retrospective cohort of 20 inlay PFA, 11 PFA with an elevated Insall-Salvati index and an increased patello-femoral congruence angle showed an initial satisfactory result, but presented thereafter with recurrent pain and "clunk" phenomena. They were all revised after a median time of 25 months (range 8-28 months) into an onlay technique PFA and analyzed for their failure mode and revision technique. RESULTS: Clinical symptoms such as clunking, as well as abraded areas craniolateral of the inlay implant found intraoperatively, were the main observations of this study. The modified Insall-Salvati index (mISI) was significantly higher in the revised knees compared to the unrevised (median 1.8 versus 1.6; p = 0.041). VAS and KSS significantly improved after revision (median VAS reduction in pain of 4.0 points, median KSS improvement of 20.0 points; p < 0.05). CONCLUSION: Patients with high-normal patellar height index or patella alta, as well as a craniolateral type of arthritis with additional lateralization, should be considered contra-indicated for an inlay technique PFA. They could be considered for a PFA system reaching further proximal into the distal femur. An onlay PFA can be an option for early revision of failed inlay implants. The clinical relevance of this study is that patella alta and patellar subluxation are more difficult to adjust for with an inlay PFJ component. LEVEL OF EVIDENCE: Level IV. PMID- 29785446 TI - Digital droplet PCR-based absolute quantification of pre-transplant NPM1 mutation burden predicts relapse in acute myeloid leukemia patients. AB - Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable ("minimal") residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves. Using ddPCR, we analyzed pre-transplant peripheral blood and bone marrow of 51 NPM1-mutated acute myeloid leukemia patients transplanted in complete remission or complete remission with incomplete recovery. Mutated NPM1 measurable residual disease-positive patients had higher cumulative incidence of relapse (P < 0.001) and shorter overall survival (P = 0.014). Restricting the analyses to patients receiving non-myeloablative conditioning, mutated NPM1 measurable residual disease positivity is associated with higher cumulative incidence of relapse (P < 0.001) and shorter overall survival (P = 0.006). Positive mutated NPM1 measurable residual disease status determined by ddPCR before allogeneic stem cell transplantation is associated with worse prognosis independent of other known prognostic markers-also for those receiving non-myeloablative conditioning. In the future, mutated NPM1 measurable residual disease status determined by ddPCR might guide treatment and improve patients' outcomes. PMID- 29785449 TI - Parkinson's disease increases the risk of perioperative complications after total knee arthroplasty: a nationwide database study. AB - PURPOSE: Therefore, the purpose of this study was to evaluate the short-term perioperative outcomes of PD patients who underwent total knee arthroplasty (TKA). We specifically evaluated: (1) perioperative surgical and medical complications; (2) lengths of stay (LOS); and (3) total hospital charges. METHODS: The Nationwide Inpatient Sample was used to identify PD patients who underwent TKA between 2002 and 2013. To control for potential confounders, PD TKA and non-PD TKA patients were propensity score matched (1:3) based on age, sex, ethnicity, Charlson Comorbidity Index, and insurance type. A total of 31,979 PD and 95,596 non-PD TKA patients were included. RESULTS: PD patients had a 44% higher risk of suffering from any complication (OR 1.44; 95% CI 1.35-1.54), a 45% increased risk for any medical complication (OR 1.45; 95% CI 1.36-1.55), and a 9% higher risk for any surgical complication (OR 1.09; 95% CI 0.84-1.41). Compared to the matched cohort, PD patients had a mean LOS that was 6.5% longer (95% CI 5.46-7.54) and mean total hospital charges that were 3.05% higher (95% CI 1.99 4.11). CONCLUSIONS: PD patients are more likely to have postoperative complications, longer LOS, and higher costs after TKA than non-PD TKA patients. Since many of these complications can be prevented, a team-based multi-specialty patient optimization is needed. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 29785450 TI - Light intensity physical activity increases and sedentary behavior decreases following total knee arthroplasty in patients with osteoarthritis. AB - PURPOSE: To describe objectively measured changes in the volume and pattern of physical activity and sedentary behavior in patients undergoing total knee arthroplasty for osteoarthritis. METHODS: Physical activity and sedentary behavior were measured in patients (13 males, 76 females) with a mean age of 64 years (range 55-80) and end-stage osteoarthritis of the knee, using an accelerometer (ActiGraph GT3X+) for seven consecutive days (24 h/day) prior to, 6 weeks and 6 months after total knee arthroplasty. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), University of California Los Angeles (UCLA) Activity index and range of motion (ROM) were also assessed. RESULTS: Proportion of time spent in sedentary behavior decreased from baseline to 6 months (mean 70.1 vs. 64.0%; p = 0.009) and the interruptions to sedentary behavior improved between baseline and 6 months after total knee arthroplasty (mean 85.0-93.0 breaks/day, p = 0.014). Proportion of time spent in light physical activity increased from baseline to 6 months after total knee arthroplasty (29.0 vs. 34.8%; p = 0.008). There was no change in time spent in moderate to vigorous physical activity after total knee arthroplasty. WOMAC (median 71.0 vs. 4.0, p < 0.001), UCLA (median 2.0 vs. 5.0, p < 0.001) as well as ROM [median (0.0 degrees -90.0 degrees ) vs. (0.0 degrees -110 degrees ), p < 0.05] scores improved between baseline and 6 months after total knee arthroplasty. CONCLUSION: Clinically, functional improvements in patients following total knee arthroplasty may be assessed by objectively measuring changes in low intensity activity behaviors. The use of accelerometers in this study gives new insights into activity accumulation patterns in a clinical population and highlights their use in determining a behavioral response to an intervention. LEVEL OF EVIDENCE: II. PMID- 29785451 TI - Lipidus migrans-a radiology imaging feature after ankle injury. AB - We present an uncommon imaging feature with fluid fat tracking within the tendon sheath of the flexor hallucis longus (FHL) after traumatic injury to the ankle joint. We propose a coined medical term "lipidus migrans" to define the presence of floating fat in a tendon sheath. This is due to lipohemarthrosis from intra articular fracture of the ankle with leakage of fluid fat into the tendon sheath. Communication between the FHL tendon sheath and ankle joint can occur in up to 25% of patients. Radiologists should be aware of the presence of lipidus migrans as a potential posttraumatic complication after intra-articular ankle fracture and that fat in the tendon sheath may mimic fracture fragments or even a tendon sheath tumor. PMID- 29785453 TI - Adding sutures to tack fixation of mesh does not lower the re-operation rate after laparoscopic ventral hernia repair: a nationwide cohort study. AB - BACKGROUND: There are various ways of fixating an intraperitoneal onlay mesh during a laparoscopic ventral hernia repair. The risk of complications is high, and around 22% of the hernias will recur within 3.5 years. The aim of this study was to assess if sutures in addition to tack fixation would reduce the re operation rate for recurrence compared with permanent tacks without sutures. METHODS: This study was based on the data from the nationwide Danish Ventral Hernia Database, which contains information of ventral hernia repairs from all hospitals in Denmark. Two different cohorts of patients were created and analyzed separately. The primary outcome was the re-operation rate for recurrence, analyzed with the Cox regression model and illustrated with a Kaplan-Meier plot adjusted for confounders. The follow-up period was defined as months from the first hernia repair to re-operation for recurrence, death, or the 1st of June 2017. RESULTS: The first cohort included 598 patients with absorbable sutures and tacks compared with 1793 patients with permanent tacks. The second cohort included 72 patients with permanent sutures and tacks compared with 216 patients with permanent tacks. In the suture groups, the tack material was either permanent or absorbable. When adjusting for possible confounders in the Cox regression model, there were no significant differences in the re-operation rate for recurrence between the groups in the two cohorts. CONCLUSION: Adding sutures, either absorbable or permanent, to tack fixation of mesh during laparoscopic ventral hernia repair did not influence the re-operation rates for recurrence. PMID- 29785452 TI - Local recurrence of soft-tissue sarcoma: issues in imaging surveillance strategy. AB - Soft-tissue sarcomas pose diagnostic and therapeutic challenges to physicians, owing to the large number of subtypes, aggressive tumor biology, lack of consensus on management, and controversy surrounding interval and duration of surveillance scans. Advances in multidisciplinary management have improved the care of sarcoma patients, but controversy remains regarding strategies for surveillance following definitive local control. This review provides an updated, comprehensive overview of the current understanding of the risk of local recurrence of soft-tissue sarcoma, by examining the literature based on features such as histological type and grade, tumor size, and resection margin status, with the aim of helping clinicians, surgeons, and radiologists to develop a tailored approach to local imaging surveillance. PMID- 29785454 TI - The roles of Arabidopsis HSFA2, HSFA4a, and HSFA7a in the heat shock response and cytosolic protein response. AB - Previously, we found that Arabidopsis plants transformed with a construct containing the promoter of Oshsp17.3 from rice fused to the beta-glucuronidase gene (GUS), Oshsp17.3Pro::GUS (Oshsp17.3p), showed a GUS signal after heat shock (HS) or azetidine-2-carboxylic acid (AZC) treatment. HS and AZC trigger the heat shock response (HSR) and cytosolic protein response (CPR), respectively, in the cytosol by modulating specific heat shock factor (HSF) activity. Here we further identified that AtHSFA2 (At2g26150), AtHSFA7a (At3g51910), AtHSFB2a (At5g62020), and AtHSFB2b (At4g11660) are HS- and AZC-inducible; AtHSFA4a (At4g18880) is AZC inducible; and AtHSFA5 (At4g13980) is less AZC- and HS-inducible. To investigate the roles of these 6 AtHSFs in the HSR or CPR, we crossed two independent Oshsp17.3p transgenic Arabidopsis plants with the AtHSF-knockout mutants athsfa2 (SALK_008978), athsfa4a (GABI_181H12), athsfa5 (SALK_004385), athsfa7a (SALK_080138), athsfb2a (SALK_137766), and athsfb2b (SALK_047291), respectively. As compared with the wild type, loss-of-function mutation of AtHSFA2, AtHSFA4a, and AtHSFA7a decreased HS and AZC responsiveness, so these 3 AtHSFs are essential for the HSR and CPR. In addition, loss-of-function results indicated that AthsfB2b is involved in regulating the HSR in Arabidopsis. Furthermore, analysis of the relative GUS activity of two double knockout mutants, athsfA2/athsfA4a and athsfA2/athsfA7a, revealed that AtHSFA2, AtHSFA4a, and AtHSFA7a function differentially in the HSR and CPR. Transcription profiling in athsf mutants revealed positive or negative transcriptional regulation among the 6 AtHSFs in Arabidopsis plants under HS and AZC conditions. Tunicamycin treatment demonstrated that these 6 AtHSFs are not involved in the unfolded protein response. PMID- 29785455 TI - Robotic-assisted laparoscopic median arcuate ligament release: 7-year experience from a single tertiary care center. AB - BACKGROUND: Despite previous reports of robotic-assisted laparoscopic release for median arcuate ligament syndrome (MALS), the safety and efficacy profile of this approach has been difficult to establish due to the rarity of this diagnostic entity. We aim to present our experience from a tertiary minimally invasive surgery referral center. METHODS: A case series was performed whereby all patients who underwent robotic-assisted MAL release from July 2010 to July 2017 at our institution were included. Diagnosis of MALS was made based on consideration of symptom presentation, celiac artery duplex ultrasound, and corresponding findings on Computed Tomography (CT) or Magnetic Resonance Angiography (MRA). Outcomes up until the most recent clinic follow-up were reviewed. RESULTS: A total of 13 patients underwent robotic-assisted MAL release. Patients' age ranged from 16 to 71 years (mean 38 years) and consisted primarily of females (76.9%). Most common presenting symptoms included postprandial pain (76.9%), weight loss (76.9%), nausea and vomiting (76.9%). Mean symptom duration was 3 years (range 1-10 years). No intraoperative complications. None required conversion to open surgery. One case required a conversion back to laparoscopy due to anatomical complexity. The mean operative time for successfully completed robotic cases was 94.6 min (range 52-120 min), and for all cases including converted case was 103.5 min (52-210 min). Mean follow-up duration was 19.7 months (range 1-77 months). During subsequent follow-up, a 30-day readmission rate of 23.1% was observed. All but one of the patients experienced prompt symptom improvement. Four patients had symptom recurrence during follow-up. CONCLUSIONS: Our experience demonstrates that the robotic-assisted approach to MAL release may be safe and efficacious in selected patients. Prospective comparative studies are required to further evaluate its outcomes against conventional laparoscopic approach, the current gold standard. PMID- 29785456 TI - Methylene blue fluorescence of the ureter during colorectal surgery. AB - BACKGROUND: Iatrogenic ureteric injury is a serious complication of colorectal surgery. Incidence is estimated to be between 0.3 and 1.5%. Of all ureteric injuries, 9% occur during colorectal procedures. Ureteric stents are utilised as a method to reduce the risk of injury; however, these are not without risk and do not guarantee prevention of injury. Fluorescence is a safe and effective alternative for intraoperative ureteric localisation. This proof of principle study aims to assess the use of methylene blue to fluoresce the ureter during colorectal surgery. METHOD: Patients undergoing elective colorectal surgery were included in this open label, non-randomised study. Methylene blue was administered intravenously at varying doses (0.25-1 mg/kg) over 5 min, 10-15 min prior to entering 'ureteric territory.' Fluorescence was assessed using the PINPOINT Deep Red laparoscopic system at fixed time points by the surgeon and an independent observer. RESULTS: 42 patients received methylene blue; 2 patients were excluded from analysis. Of the 69 ureters assessed, 64 were seen under fluorescence. Of these, 14 were not visible under white light. 50 ureters were observed with both fluorescence and white light with 14 of these being seen earlier with fluorescence. In ten cases, fluorescence revealed the ureter to be in a different location than suspected. CONCLUSION: Fluorescence is a promising method to allow visualisation of the ureter, where it is not identified easily under standard operative conditions, thereby improving safety and reducing operative time and difficulty. PMID- 29785457 TI - A novel method of intracorporeal end-to-end gastrogastrostomy in laparoscopic pylorus-preserving gastrectomy for early gastric cancer, including a unique anastomotic technique: piercing the stomach with a linear stapler. AB - BACKGROUND: Delta-shaped anastomosis is usually applied for an intracorporeal gastrogastrostomy in totally laparoscopic pylorus-preserving gastrectomy (TLPPG). However, the remnant stomach is slightly twisted around the anastomosis because it connects in side-to-side fashion. To realize an intracorporeal end-to-end gastrogastrostomy using an endoscopic linear stapler, we invented a novel method including a unique anastomotic technique. MATERIALS AND METHODS: In this new approach, we first made small gastrotomies at the greater and lesser curvatures of the transected antrum and then pierced it using an endoscopic linear stapler. After the pierced antrum and the proximal remnant stomach were mechanically connected, the gastrotomies and stapling lines were transected using an endoscopic linear stapler, creating an intracorporeal end-to-end gastrogastrostomy. We have named this technique the "piercing method" because piercing the stomach is essential to its implementation. Between October 2015 and June 2017, 26 patients who had clinically early gastric cancer at the middle third of the stomach without clinical evidence of lymph node metastasis underwent TLPPG involving the novel method. RESULTS: The 26 patients successfully underwent an intracorporeal mechanical end-to-end gastrogastrostomy by the piercing method. The median operation time of the 26 patients was 272 min (range 209-357 min). With the exception of one gastric stasis, no problems associated with the piercing method were encountered during and after surgery. CONCLUSION: The piercing method can safely create an intracorporeal mechanical end-to-end gastrogastrostomy in TLPPG. Piercing the stomach using an endoscopic linear stapler is a new technique for gastrointestinal anastomosis. This method should be considered if the surgical aim is creation of an intracorporeal end-to-end gastrogastrostomy in TLPPG. PMID- 29785458 TI - High-resolution standardization reduces delay due to workflow disruptions in laparoscopic cholecystectomy. AB - BACKGROUND: Optimal resource utilization in high-cost environments like operating theatres is fundamental in today's cost constrained health care systems. Interruptions of the surgical workflow, i.e. microcomplications (MC), lead to prolonged procedure times and higher costs and can be indicative of surgical mistakes. Reducing MC can improve operating room efficiency and prevent intraoperative complications. We, therefore, aimed to evaluate the impact of a high-resolution standardized laparoscopic cholecystectomy protocol (HRSL) on operative time and intraoperative interruptions in a teaching hospital. METHODS: HRSL consisted of a detailed stepwise protocol for the procedure, supported by a teaching video, both to be reviewed as mandatory preparation by each team member before surgery. Audio-video records of laparoscopic cholecystectomies were reviewed regarding type, frequency and duration of MC before and after implementation of HRSL. RESULTS: Thirty-nine (20 control and 19 HRSL) audio-video records of laparoscopic cholecystectomies with a total duration of 51.36 h (28.92 pre 22.44 post) were reviewed. The majority of operations (86%) were performed by teams who had completed less than 10 procedures together previously. Communication-related interruptions and instrument changes accounted for the majority of MC. Median frequency and duration of MC were 95 events/h and 15.6 min/h, respectively, of surgery pre-intervention. With HRSL this was reduced to 76 events/h and 10.6 min/h of operating. In multivariable analysis, HRSL was an independent predictor for shorter delay and lower frequency of MC [percentage decrease 27% (95% CI 18-35%), resp. 30% (95% CI 19-40%)]. Procedure-related risk factors for the longer delay due to MC in multivariable analysis were less experience of the surgeon and intraoperative adhesiolysis. CONCLUSIONS: HRSL is effective in reducing delays due to MC in a teaching institution with limited team experience. These findings should be tested in larger potentially cluster randomized controlled trials. The trial has been registered with clinicaltrials.gov: NCT03329859. PMID- 29785459 TI - Intracorporeal delta-shaped gastroduodenostomy in reduced-port robotic distal subtotal gastrectomy: technical aspects and short-term outcomes. AB - BACKGROUND: Gastroduodenostomy is preferred as a method of reconstruction following distal subtotal gastrectomy. However, in initial reports on reduced port gastrectomy, gastroduodenostomy has rarely been performed therein because of technical difficulties. The present study describes a novel intracorporeal gastroduodenostomy technique applicable during reduced-port robotic distal subtotal gastrectomy. METHODS: Data were retrospectively reviewed for cases of reduced-port (three-port) robotic distal subtotal gastrectomy with intracorporeal delta-shaped gastroduodenostomy performed from February 2016 to December 2016. The reduced-port approach used a Single-SiteTM port via a 25-mm infraumbilical incision and two additional ports. We performed intracorporeal gastroduodenostomy using a 45-mm robotic or laparoscopic endolinear stapler. All staplers were inserted via a port on the left lower abdomen. RESULTS: In our initial experience with intracorporeal gastroduodenostomy, 28 consecutive patients underwent successful surgery with the technique without needing to convert to open, laparoscopic, or conventional five-port robotic surgery. Mean operation time was 201.1 min (110-282 min), and no major complications, including anastomosis related problems, were recorded. CONCLUSIONS: Intracorporeal delta-shaped gastroduodenostomy was safely and feasibly applied during reduced-port robotic gastrectomy with acceptable operative outcomes and no major complications. Intracorporeal gastroduodenostomy should be considered during reduced-port distal subtotal gastrectomy. PMID- 29785460 TI - Rapid measurement of long-range distances in proteins by multidimensional 13C-19F REDOR NMR under fast magic-angle spinning. AB - The ability to simultaneously measure many long-range distances is critical to efficient and accurate determination of protein structures by solid-state NMR (SSNMR). So far, the most common distance constraints for proteins are 13C-15N distances, which are usually measured using the rotational-echo double-resonance (REDOR) technique. However, these measurements are restricted to distances of up to ~ 5 A due to the low gyromagnetic ratios of 15N and 13C. Here we present a robust 2D 13C-19F REDOR experiment to measure multiple distances to ~ 10 A. The technique targets proteins that contain a small number of recombinantly or synthetically incorporated fluorines. The 13C-19F REDOR sequence is combined with 2D 13C-13C correlation to resolve multiple distances in highly 13C-labeled proteins. We show that, at the high magnetic fields which are important for obtaining well resolved 13C spectra, the deleterious effect of the large 19F chemical shift anisotropy for REDOR is ameliorated by fast magic-angle spinning and is further taken into account in numerical simulations. We demonstrate this 2D 13C-13C resolved 13C-19F REDOR technique on 13C, 15N-labeled GB1. A 5-19F-Trp tagged GB1 sample shows the extraction of distances to a single fluorine atom, while a 3-19F-Tyr labeled GB1 sample allows us to evaluate the effects of multi spin coupling and statistical 19F labeling on distance measurement. Finally, we apply this 2D REDOR experiment to membrane-bound influenza B M2 transmembrane peptide, and show that the distance between the proton-selective histidine residue and the gating tryptophan residue differs from the distances in the solution NMR structure of detergent-bound BM2. This 2D 13C-19F REDOR technique should facilitate SSNMR-based protein structure determination by increasing the measurable distances to the ~ 10 A range. PMID- 29785461 TI - Clinical significance of appendiceal diverticulum: a significant marker for appendiceal neoplasia in Australian patients. AB - INTRODUCTION: Diverticula of the appendix (DA) have a reported incidence of up to 2.1%. They are primarily detected incidentally, through imaging and intraoperative or histologic diagnosis. This study's objective was to examine the prevalence of DA, and its relationship with inflammation and neoplasia, as well as review the literature with respect to clinical outcomes and ability to identify DA preoperatively. METHODOLOGY: A retrospective search of all patients undergoing an appendicectomy for right lower quadrant pain at a single institution between 2004 and 2017 was conducted. Histopathology reports for evidence of DA, location of the DA, presence of inflammation, and any relationship between DA and neoplasms (adenoma, carcinoma, carcinoid, lymphoma, and mucinous neoplasm) within the appendix were reviewed. Clinical notes, operative records, and preoperative imaging were also reviewed. RESULTS: Two thousand seven hundred eleven patient were included in the study, with a mean age of 34 years, with acute appendicitis found in 82.5%. 31.6% of patients with DA had associated inflammation of the DA. DA was present in 57 patients (2.1%), with 55 patients in the total cohort having neoplasia (2.0%). Patients with DAs were ten times more likely to have appendicular neoplasm than patients without a DA (17.5 vs 1.8%; p < 0.0001, OR 11.8 95%, CI 5.6-24.8). CONCLUSION: This is the first Australian study demonstrating DAs are a significant marker of appendiceal neoplasm. Appendicectomy in all incidentally discovered diverticulum should be considered. Due to a paucity of data, research is required into this area to assess for the need for endoscopy following diagnosis. PMID- 29785462 TI - The prognostic value of tumour stroma ratio and tumour budding in stage II colon cancer. A nationwide population-based study. AB - PURPOSE: High-risk patients with stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better stratification. We investigated the prognostic value of tumour stroma ratio (TSR) and tumour budding (TB). METHODS: A nationwide population-based cohort of 573 patients with stage II CC was included. TSR was scored on hematoxylin and eosin sections as low TSR (> 50% stroma) and high TSR (<= 50% stroma). TB was evaluated in hotspots on pan-cytokeratin stained sections in 10 high power fields (HPF) at the invasive front and classified by the mean number of buds per HPF as high grade budding (>= 10 buds) or low-grade budding (< 10 buds). The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Low TSR was associated with worse RFS (HR = 1.342 (95% CI 1.006-1.791), p = 0.045) and OS (HR = 1.376 (95% CI 1.016 1.862), p = 0.039). Furthermore, an association was found between low TSR and microsatellite stabile tumours (p < 0.001). The mean number of buds per HPF was associated to TSR with increasing number of buds related to a lower TSR (p = 0.026). No statistically significant prognostic impact of TB regarding OS or RFS was detected. CONCLUSIONS: TSR provided valuable prognostic information, and adding TSR to the current risk stratification may contribute to better patient selection. The estimates of TSR and TB were found to be associated, but no prognostic value of TB was documented. PMID- 29785463 TI - The North American Forest Database: going beyond national-level forest resource assessment statistics. AB - Forests cannot be managed sustainably without reliable data to inform decisions. National Forest Inventories (NFI) tend to report national statistics, with sub national stratification based on domestic ecological classification systems. It is becoming increasingly important to be able to report statistics on ecosystems that span international borders, as global change and globalization expand stakeholders' spheres of concern. The state of a transnational ecosystem can only be properly assessed by examining the entire ecosystem. In global forest resource assessments, it may be useful to break national statistics down by ecosystem, especially for large countries. The Inventory and Monitoring Working Group (IMWG) of the North American Forest Commission (NAFC) has begun developing a harmonized North American Forest Database (NAFD) for managing forest inventory data, enabling consistent, continental-scale forest assessment supporting ecosystem level reporting and relational queries. The first iteration of the database contains data describing 1.9 billion ha, including 677.5 million ha of forest. Data harmonization is made challenging by the existence of definitions and methodologies tailored to suit national circumstances, emerging from each country's professional forestry development. This paper reports the methods used to synchronize three national forest inventories, starting with a small suite of variables and attributes. PMID- 29785464 TI - Contribution of Cochlear Compression to Discrimination of Rippled Spectra in On- and Low-frequency Noise. AB - The goal of the study was to assess cochlear compression when rippled-spectrum signals are perceived in noise assuming that the noise might produce both masking and confounding effects. In normal listeners, discrimination between rippled signals with and without ripple phase reversals was assessed in background noise. The signals were band-limited (0.5 oct at a - 6-dB level) rippled noise centered at 2 kHz, with a ripple density of 3.5 oct-1. The noise (masker) was band-limited nonrippled noise centered at either 2 kHz (on-frequency masker) or 1 kHz (low frequency masker). The masker was simultaneously presented with the signals. Masker levels at the discrimination threshold were measured as a function of the signal level using the adaptive (staircase) two-alternative forced-choice procedure. For the on-frequency masker, the searched-for function had a slope of 0.98 dB/dB. For the low-frequency masker, the function had a slope of 1.19 dB/dB within a signal level range of 30 to 40 dB sound pressure level (SPL) and as low as 0.15 dB/dB within a signal level range of 70 to 80 dB SPL. These results were interpreted as indicating compression of responses to both the signal and on frequency masker and no compression of the effect of the low-frequency masker. In conditions when above-threshold signals are presented in simultaneous noise (the masker), cochlear compression manifests to a substantial degree despite possible confounding effects. PMID- 29785466 TI - Effect of Reassuring Information About Musculoskeletal and Mental Health Complaints at the Workplace: A Cluster Randomized Trial of the atWork Intervention. AB - Purpose The purpose of this study was to investigate the possible difference between the Modified atWork intervention (MAW) and the Original atWork intervention (OAW) on sick leave and other health related outcomes. atWork is a group intervention using the workplace as an arena for distribution of evidence based knowledge about musculoskeletal and mental health complaints. Methods A cluster randomized controlled trial with 93 kindergartens, comprising a total of 1011 employees, was conducted. Kindergartens were stratified by county and size and randomly allocated to MAW (45 clusters, 324 respondents) or OAW (48 clusters, 313 respondents). The randomization and intervention allocation processes were concealed. There was no blinding to group allocation. Primary outcome was register data on sick leave at cluster level. Secondary outcomes were health complaints, job satisfaction, social support, coping, and beliefs about musculoskeletal and mental health complaints, measured at the individual level. Results The MAW group reduced sick leave by 5.7% during the intervention year, while the OAW group had a 7.5% increase. Overall, the changes were not statistically significant, and no difference was detected between groups, based on 45 and 47 kindergartens. Compared to the OAW group, the MAW group had a smaller reduction for two of the statements concerning faulty beliefs about back pain, but believed less in the hereditary nature of depression. Conclusions The MAW did not have a different effect on sick leave at cluster level compared to the OAW. Trial registration https://Clinicaltrials.gov/ : NCT02396797. Registered March 23th, 2015. PMID- 29785467 TI - Impact of a Safe Resident Handling Program in Nursing Homes on Return-to-Work and Re-injury Outcomes Following Work Injury. AB - Purpose This study examined the impact of a Safe Resident Handling Program (SRHP) on length of disability and re-injury, following work-related injuries of nursing home workers. Resident handling-related injuries and back injuries were of particular interest. Methods A large national nursing home corporation introduced a SRHP followed by three years of training for 136 centers. Lost-time workers' compensation claims (3 years pre-SRHP and 6 years post-SRHP) were evaluated. For each claim, length of first episode of disability and recurrence of disabling injury were evaluated over time. Differences were assessed using Chi square analyses and a generalized linear model, and "avoided" costs were projected. Results The SRHP had no impact on length of disability, but did appear to significantly reduce the rate of recurrence among resident handling-related injuries. As indemnity and medical costs were three times higher for claimants with recurrent disabling injuries, the SRHP resulted in significant "avoided" costs due to "avoided" recurrence. Conclusions In addition to reducing overall injury rates, SRHPs appear to improve long-term return-to-work success by reducing the rate of recurrent disabling injuries resulting in work disability. In this study, the impact was sustained over years, even after a formal training and implementation program ended. Since back pain is inherently a recurrent condition, results suggest that SRHPs help workers remain at work and return-to work. PMID- 29785465 TI - Causes and Treatment of Acute Ischemic Stroke During Pregnancy. AB - PURPOSE OF REVIEW: Treatment recommendations for pregnancy associated ischemic stroke are scarce. This may be due to the fact that, in general, obstetricians tend not to make recommendations for stroke patients and neurologists are not commonly involved in the care of pregnant women. Herein, we review the multiple etiologies of ischemic stroke during pregnancy, considerations for diagnostic testing, and acute treatment and prevention options, including associated risks specific to the pregnant and puerperal state. RECENT FINDINGS: Intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy have been used successfully to treat pregnant women with acute ischemic stroke. Recent national guidelines recommend considering tPA use during pregnancy for moderate and severe strokes if the potential benefits offset the risks of uterine hemorrhage. Pregnancy-associated ischemic stroke is rare, but can be devastating, and recanalization therapy should not be systematically withheld. Women who are at risk for stroke should be followed carefully, and providers caring for pregnant women should be educated regarding stroke signs and symptoms. Many of the standard post stroke diagnostic modalities may be used safely in pregnancy, and primary and secondary stroke prevention therapy must be tailored to avoid fetal toxicity. PMID- 29785468 TI - Competition for electrons between mono-oxygenations of pyridine and 2 hydroxypyridine. AB - Pyridine and its heterocyclic derivatives are widely encountered in industrial wastewaters, and they are relatively recalcitrant to biodegradation. Pyridine biodegradation is initiated by two mono-oxygenation reactions that compete for intracellular electron donor (2H). In our experiments, UV photolysis of pyridine generated succinate, whose oxidation augmented the intracellular electron donor and accelerated pyridine biodegradation and mineralization. The first mono oxygenation reaction always was faster than the second one, because electrons provided by intracellular electron donors were preferentially utilized by the first mono-oxygenase; this was true even when the concentration of 2HP was greater than the concentration of pyridine. In addition, the first mono oxygenation had faster kinetics because it had higher affinity for its substrate (pyridine), along with less substrate self-inhibition. PMID- 29785469 TI - Early Detection of Cerebral Infarction After Focal Ischemia Using a New MRI Indicator. AB - Prolongation of the T2 relaxation time, an increase in T2-weighted signal intensity (T2-SI), and a decrease in the apparent diffusion coefficient (ADC) calculated from diffusion-weighted images (DWI) on magnetic resonance imaging (MRI) are conventional indicators of the vasogenic (interstitial) or cytotoxic (cellular) cerebral edema that develops after ischemic stroke. However, these parameters obtained on stroke imaging have not given us a precise threshold at which we can determine the viability or vulnerability of the tissue, allowing us to decide on an intervention that will help reversible tissue in the acute phase. Here, we introduce a new indicator-the essential diffusion coefficient or EDC, calculated from the T2-SI and ADC-that permits detection of irreversible brain damage after induction of experimental, focal cerebral ischemia. Our three-vessel occlusion (3-VO) method (Yang et al. Eur Neurol 71:4-18, 2014) was applied to investigate early changes on 7-T MRI. In the 3-VO model, which targets only a part of the cortex, animals seldom die at least within 24 h. The T2-SI and the ADC value were monitored, starting at 60 min after reperfusion, and every 30-60 min, for 10 h after the induction of focal ischemia. The region of interest (ROI) was set in each of the following: (1) the ischemic core (the dead zone); (2) the medial border area (the dying/dead mixed zone, including the ischemic penumbra); (3) the lateral border area (the surviving zone after the ischemic stress, where the rCBF is above the threshold for death); and (4) The intact area (outside the ischemic zone). The diagnosis was made by histological analysis performed 24 h after reperfusion. Significant increases in the T2-SI were observed, in ROI-1 at 1 h, in ROI-2 at 2.5 h, and in ROI-3 at 4 h post-reperfusion (1.10, 1.11, or 1.11; > 1.10, respectively, p < 0.001). Significant reductions in the ADC were also observed in ROI-1, ROI-2, and ROI-3, at 1 h post-reperfusion (0.55, 0.52, or 0.58; < 0.60, respectively, p < 0.001), indicating that both types of cerebral edema develop simultaneously in the acute phase. In the EDC analysis, from 5.0 h post-reperfusion, the value in the dying/dead zone (ROI-1 and ROI-2) was consistently reduced to < 50%, showing repeated, significant differences from the value in the surviving zone (ROI-3). A reduction in the EDC to below 50% indicated irreversible tissue damage, with transformation to cerebral infarction. We could detect a sign of cerebral infarction (initial necrosis-like irreversible lesion) as early as 5.25 h after the onset of ischemia. Although the biological time that depends on the body weight must be different between mice and humans, the earliest irreversible tissue damage or tissue destruction (to have achieved the risk of hemorrhagic transformation) that progressed after invisible or silent cell death in the ultra-acute phase, seems to occur at a similar time point. PMID- 29785470 TI - Four factor prothrombin complex concentrate for warfarin reversal in patients with left ventricular assist devices. AB - Continuous flow left ventricular assist devices (CF-LVAD) require therapeutic anticoagulation which is often interrupted for procedures or bleeding. Prior to the availability of four factor prothrombin complex concentrate (4F-PCC) in the United States, warfarin was held and its effects reversed by vitamin K or fresh frozen plasma. We evaluated the use of 4F-PCC for temporary warfarin reversal in patients with CF-LVADs and assessed outcomes. This analysis is a retrospective study of CF-LVAD patients who received 4F-PCC for warfarin reversal in the setting of bleeding or need for urgent or elective procedures. Primary outcome assessments included feasibility of administration in elective versus emergent situations, safety measured as incidence of thrombotic events, and change in INR after administration. In total, 37 CF-LVAD patients received 49 4F-PCC administrations. The average 4F-PCC dose was 1842 units (range 518-4292 units), or 22 units/kg (range 5.8-58 units/kg). 4F-PCC significantly decreased the mean INR from 2.9 to 1.7 (p < 0.0001) in 47 of 49 administrations; two patients did not have post infusion INR testing. No cases of new confirmed or suspected pump thrombosis, stroke, venous thromboembolism, arterial thrombosis, or myocardial infarction were observed within 30 days of administration of 4F-PCC. 4F-PCC administration for temporary warfarin reversal was demonstrated to be feasible, effective, and, safe in CF-LVAD patients and judged to be 96% effective in patients for whom data were available. We observed no thrombotic events attributed to use of 4F-PCC. PMID- 29785471 TI - Correction to: Effect of Sleeve Gastrectomy on Platelet Counts and Mean Platelet Volumes. AB - In the original article, in the Results section of the Abstract the text "...(10.41 +/- 1.23 fL, p > 0.001)" should be changed to "...(10.41 +/- 1.23 fL, p < 0.001)". The same error occurs on the next page of the article in the second paragraph of the Results section of the main text. PMID- 29785473 TI - Changes in Melatonin, Cortisol, and Body Temperature, and the Relationship Between Endogenous Melatonin Levels and Analgesia Consumption in Patients Undergoing Bariatric Surgery. AB - BACKGROUND: Melatonin has analgesic, anti-inflammatory, sedative, and anxiolytic properties. However, the relationship between endogenous melatonin levels and postoperative analgesic requirements has not been well elucidated in patients undergoing bariatric surgery. We studied endogenous melatonin levels, cortisol levels, body temperatures, and the relationship between the level of endogenous melatonin and postoperative morphine consumption. METHODS: The trial was conducted among 30 patients who were scheduled for laparoscopic bariatric surgery. Their ages were between 18 and 65 years and their BMIs were above 40 kg/m2. Secretion of melatonin, cortisol, and body temperature was monitored before the anesthetic induction, at 2 h intraoperatively, and at 2, 6, 10, (2:00 A.M.) and 24 h postoperatively. For each patient, morphine consumption was assessed at postoperative visits. The primary outcomes were to measure endogenous melatonin levels and to examine the relationship between these levels and morphine consumption. The secondary outcome was to observe the changes in cortisol and body temperature. RESULTS: There was a significant decrease in melatonin levels when preoperative melatonin levels were compared with intraoperative and all postoperative follow-up periods (p < 0.05). When the correlation between plasma melatonin levels and the postoperative morphine consumption of the patients was inspected, there was a significant correlation in all of the follow-up periods (p < 0.05). When preoperative cortisol levels were compared with intraoperative and postoperative cortisol levels, there was a significant difference in the follow-up periods, except two periods (p < 0.05). Body temperatures were similar in all measurement periods. CONCLUSIONS: Endogenous melatonin secretion was significantly decreased in the intraoperative and postoperative periods. Furthermore, there was a significant inverse correlation between changes in endogenous melatonin levels and morphine consumption. TRIAL REGISTRATION: Clinical Trial Number NCT03107702 from A service of the U.S. National Institutes of Health, clinicaltrials.gov. PMID- 29785472 TI - The Impacts of Gastroileostomy Rat Model on Glucagon-like Peptide-1: a Promising Model to Control Type 2 Diabetes Mellitus. AB - BACKGROUND: One of the new current treatment options for Diabetes Mellitus is about increasing glucagon-like peptide-1 (GLP-1) activity. GLP-1 with its incretin effect showed major role in glucose homeostasis. Gastroileostomy can increase GLP-1 secretion by rapid delivery of undigested food to the terminal ileum. We studied the early effects of a gastroileostomy on serum levels of GLP 1, glucose, and insulin in rats. METHODS: Gastroileostomies with side-to-side anastomosis were performed on 15 male New Zealand rats. Blood samples were obtained before and 1 week after the gastroileostomy. RESULTS: Our results showed that the rats lost a lot of weight from start (330 +/- 15 g) to the end (240 +/- 25 g) of the experiment (p = 0.048). The data analysis showed that the gastroileostomy surgery elevates the level of GLP-1in plasma significantly (89.1852 vs. 177.440 respectively; p < 0.001) and caused a significant decrease in plasma glucose as well (92.00 and 66.29 mg/dL respectively; p < 0.001). However, the insulin state elevated after the surgery significantly (8.03 vs. 9.89; p < 0.001). CONCLUSION: In this study, we showed the effectiveness of gastroileostomy treatment to decrease body weight and plasma glucose with increased GLP-1 in rats. This small rat model suggests the potential of this surgery to treat type 2 diabetes mellitus. PMID- 29785474 TI - Medical Toxicology Fellowship Training Is Available to Applicants from Many Specialties. PMID- 29785475 TI - Cohort Study of Psychiatric Adverse Events Following Exposure to Levonorgestrel Containing Intrauterine Devices in UK General Practice. AB - INTRODUCTION: Intrauterine devices are implantable contraceptives of which some brands steadily release levonorgestrel over an extended time period. Exposure to a levonorgestrel-releasing intrauterine device has been associated with depression and, more recently, a connection to anxiety, panic attacks, sleep problems and restlessness has been suggested. This study uses data from the THIN database of UK general practice to investigate these suggestions. METHODS: A cohort study was performed to compare the incidence of psychiatric adverse events between groups of women who were new users of levonorgestrel-releasing and non hormonal intrauterine devices. Hazard ratios for the first occurrence of psychiatric symptoms or prescriptions of disease-specific treatments were calculated on an intention-to-treat basis using a proportional hazards model. RESULTS: Significant associations were found between levonorgestrel exposure and records of anxiety (hazard ratio = 1.18; 95% confidence interval 1.08-1.29) and sleep problems (hazard ratio = 1.22; 95% confidence interval 1.08-1.38) in women without a prior record of these events. No significant associations were found for panic attacks or restlessness. Clear baseline differences in clinical characteristics and age between the groups were present. These were included in the model as potential confounding factors. CONCLUSION: Statistically significant associations of levonorgestrel exposure with anxiety and sleep problems were observed. Substantive differences in baseline characteristics of the treated groups make robust conclusions difficult but the results strongly suggest that additional studies are warranted. PMID- 29785476 TI - Vaccinia Virus Protein C6: A Multifunctional Interferon Antagonist. AB - Vaccinia virus (VACV) is the prototypic member of the Orthopoxvirus genus of the Poxviridae. It is also the live vaccine that was used to eradicate smallpox. Like other poxviruses, VACV replicates in the cytoplasm and has a large double stranded (ds)DNA genome and a complex virion. Approximately, half of the VACV genes are nonessential for virus replication in cell culture but encode a remarkable array of immunomodulators that antagonise the innate immune response to virus infection. This short review concerns one such protein, C6, that is a multifunctional inhibitor of interferon. C6 can both diminish the production of interferon and inhibit interferon-induced signalling and thereby the expression of interferon-stimulated genes. PMID- 29785477 TI - Significance of Vi Negative Isolates of Salmonella Enterica Serovar Typhi. AB - Typhoid is a major global disease. The causative agent, Salmonella enterica serovar Typhi (S. Typhi) has a capsular antigen called Vi antigen which is traditionally considered to be the main cause of virulence. All the current vaccines are based on Vi antigen. However, the realization of the fact that there are S. Typhi strains which lack Vi antigen but still exist naturally and can cause disease has stirred great scientific interest. It is also interesting to note that their relative prevalence is affected by climatic conditions. Now it is established that Vi positive and Vi negative S. Typhi have different modes of pathogenesis; and as recent studies suggest, different structure of polysaccharide antigens. This means that current vaccines are not effective against a significant number of S. Typhi strains which not only affect the success of vaccination programs but also help in rapid emergence of Vi negative S. Typhi due to natural selection. The focus should be on vaccines based on antigens which are universally present in all S. Typhi. One such candidate is O specific polysaccharides (OSPs). Successful attempts have been made to prepare conjugate vaccines based on OSPs. PMID- 29785478 TI - Changing Trend of Infectious Diseases in Nepal. AB - Many infectious/communicable diseases (IDs) are endemic in Nepal. Until a decade and half ago, IDs were the major cause of both morbidity and mortality accounting 70% for both. However, as a result of various preventive measures implemented by both the state and non-state actors, the overall IDs have shown a changing (declining) trend. The most impressive decline has been seen in the intestinal helminth infection. Though the overall burden of IDs is decreasing, several newer infectious diseases (emerging infections) namely, dengue fever, scrub typhus, influenza (H5N1 and H1N1), and others are posing a great public health problem. On the other hand, though sporadic, outbreaks of endemic diseases together with HIV-TB coinfection and infection with drug resistance microbes during recent years have constituted a serious public health as well as medical problem. On the contrary, with the decline of IDs, noninfectious diseases (noncommunicable disease, NCD) namely, diabetes, cancer (and cancer therapy), and others are on the rise particularly in urban areas. Hence, currently Nepal is trapped in "double burden" of diseases. Risk of opportunistic infection has increased in immunocompromised person with NCD. To address the present situation, the multi sectoral plan and strategies developed must be implemented effectively. PMID- 29785479 TI - NGSPanPipe: A Pipeline for Pan-genome Identification in Microbial Strains from Experimental Reads. AB - Recent advancements in sequencing technologies have decreased both time span and cost for sequencing the whole bacterial genome. High-throughput Next-Generation Sequencing (NGS) technology has led to the generation of enormous data concerning microbial populations publically available across various repositories. As a consequence, it has become possible to study and compare the genomes of different bacterial strains within a species or genus in terms of evolution, ecology and diversity. Studying the pan-genome provides insights into deciphering microevolution, global composition and diversity in virulence and pathogenesis of a species. It can also assist in identifying drug targets and proposing vaccine candidates. The effective analysis of these large genome datasets necessitates the development of robust tools. Current methods to develop pan-genome do not support direct input of raw reads from the sequencer machine but require preprocessing of reads as an assembled protein/gene sequence file or the binary matrix of orthologous genes/proteins. We have designed an easy-to-use integrated pipeline, NGSPanPipe, which can directly identify the pan-genome from short reads. The output from the pipeline is compatible with other pan-genome analysis tools. We evaluated our pipeline with other methods for developing pan-genome, i.e. reference-based assembly and de novo assembly using simulated reads of Mycobacterium tuberculosis. The single script pipeline (pipeline.pl) is applicable for all bacterial strains. It integrates multiple in-house Perl scripts and is freely accessible from https://github.com/Biomedinformatics/NGSPanPipe . PMID- 29785480 TI - Potential Treatment Options in a Post-antibiotic Era. AB - Following the Golden Age of antibiotic discovery in the previous century, the rate of antibiotic discovery has plummeted during the past 50 years while the incidence of antimicrobial resistance is ever-increasing. Presently, humankind is forced to address a major public health threat in the form of multiple drug resistance and urgent action is required to halt the advent of a post-antibiotic era. This chapter aims to draw the attention to the escalating global crisis of antimicrobial resistance fueled by the irresponsible use of antibiotics in healthcare and animal production sectors. The merits of alternative prevention and treatment options, including vaccines, herbal products, bacteriophages, and improved biosecurity measures are also discussed. PMID- 29785481 TI - Encapsulation of Theophylline in Gelatin A-Pectin Complex Coacervates. AB - The present study aims at synthesizing gelatin A-pectin complex coacervates and encapsulation of theophylline in the polymer system. Variation and optimization of different reaction parameters such as pH, ratio between the polymers and cross linker concentration was carried out to attain higher product yield. Relative viscosity, turbidity and UV-visible measurements were done for optimization. The optimum ratio between gelatin A-pectin was fixed at weight ratio 42:8 and pH=3.5. It was further observed that adhesion between the microcapsules decreased by the use of sodium carboxymethyl cellulose (SCMC) to the coacervate. The synthesized microcapsules were characterized by using spectroscopic techniques to assess their formation, drug loading and chemical interaction between theophylline and coacervate. Scanning electron microscopy (SEM) revealed the formation of microcapsules. Study relating to the encapsulation efficiency and swelling of the complex coacervates were also carried out. PMID- 29785482 TI - Characterization and Antimicrobial Property of Some Heavy Metals Containing Ayurvedic Drugs. AB - Ayurvedic medicines are often used in different formulations, the heavy metals, which are generally referred to as being toxic. In this work, we report on the physicochemical characterization and biological activity of some typical Ayurvedic drugs available in the market that contain arsenic, mercury and lead with the emphasis on their antibacterial performance. Among the formulations studied, some of the drugs with 'amorphous' texture (and higher solubility) were found quite active against some bacterial strains whereas the formulations possessing crystalline texture (and low solubility) were found practically ineffective. The moderate activity of some drugs against Gram-negative bacteria fairly suggested the presence of the small-sized polar molecules which was also supported by the FTIR spectroscopic data. PMID- 29785483 TI - Application of Metallic Nanomaterials in Nanomedicine. AB - In this chapter, we explain why metallic nanomaterials are used in nanomedicine. We have shown that the electron density in metallic nanomaterials oscillates and creates electron density waves. When laser light falls on metallic nanoparticles, light interacts with electron density waves. According to Einstein, light, which is electromagnetic waves, consists of particles called photons. Similarly, electron density waves are also made of particles called surface plasmons. Therefore, photons from laser light and surface plasmons from metallic nanostructures interact with each other and create new particles called surface plasmon polaritons. These new particles produce an intense light near the surface of metallic nanomaterials. We showed that this intense light is important in the application of metallic nanomaterials in nanomedicine. Further, we have applied metallic nanoparticles, single metallic nanoshells and double metallic nanoshells for treatment of cancer and detection of smaller tumors. PMID- 29785484 TI - Challenges in Malaria Management and a Glimpse at Some Nanotechnological Approaches. AB - Malaria is a devastating infectious disease transmitted by mosquitoes, affecting millions of people and killing about half a million children each year. Despite tremendous progress in the control and elimination of malaria within the past years, there are still considerable challenges to be solved. To name a few, drug resistant parasites, insecticide-resistant mosquitoes and the difficulty to formulate a potent malaria vaccine need to be addressed with new strategies to achieve the final goal of malaria eradication. Nanotechnology-researching and designing innovative structures at the nanoscale-is a promising contemporary technology that is being applied to a vast number of biomedical problems. In the case of malaria, nanotechnology provides tools to design strategies to target drug molecules to specific stages of the parasite, treat drug-resistant parasites, resolve severe malaria, increase vaccine efficacies and combinations thereof. This chapter introduces malaria, discusses current challenges of malaria control and relates these challenges to some potential solutions provided by the nanotechnology field. PMID- 29785485 TI - Peg-manipulation capabilities of middle-aged adults have a greater influence on pegboard times than those of young and old adults. AB - Declines in manual dexterity are frequently quantified as the time it takes to complete the grooved pegboard test. The test requires individuals to manipulate 25 pegs, one at a time, by removing them from a well and inserting them into a prescribed hole. The manipulation of each peg involves four phases: selection, transport, insertion, and return. The purpose of our study was to compare the times to complete the four phases of peg manipulation and the forces applied to the pegboard during peg insertion as young, middle-aged, and old adults performed the grooved pegboard test. The relative significance of the peg-manipulation attributes for 30 young (24.0 +/- 4.4 years), 15 middle-aged (46.5 +/- 6.5 years), and 15 old (70.4 +/- 4.0 years) adults was assessed with a multiple regression analysis. The grooved pegboard test was performed on a force plate. Pegboard times for the old adults (81 +/- 17 s) were longer than those for young (56 +/- 7 s) and middle-aged (58 +/- 11 s) adults. Regression analysis indicated that the explanatory variables for the pegboard times of young (R2 = 0.33) and middle-aged (R2 = 0.78) adults were the times for the peg insertion and return phases, whereas the predictors for old adults (R2 = 0.49) were the times for the peg selection and transport phases. The relative influence of peg-manipulation capabilities on a pegboard test of manual dexterity was greater for middle-aged adults than for young and old adults. PMID- 29785486 TI - Radiation-induced bystander effect in large Japanese field mouse (Apodemus speciosus) embryonic cells. AB - Although evidence suggests that ionizing radiation can induce the bystander effect (radiation-induced bystander effect: RIBE) in cultured cells or mouse models, it is unclear whether the effect occurs in cells of wild animals. We investigated medium-mediated bystander micronucleus (MN) formation and DNA damage in un-irradiated cells from a large Japanese field mouse (Apodemus speciosus). We isolated four clones of A. speciosus embryonic fibroblasts (A603-1, A603-2, A603 3, and A603-4) derived from the same mother, and examined their radiation sensitivity using the colony-forming assay. A603-3 and A603-4 were similar, and A603-1 and A603-2 were highly sensitive compared with A603-3 and A603-4. We examined RIBE in the four clones in autologous medium from cell cultures exposed to 2 Gy X-ray radiation (irradiated cell conditioned medium: ICCM). We only observed increased MN prevalence and induction of DNA damage foci in A603-1 and A603-3 cells after ICCM transfer. The ICCM of A603-3 (RIBE-induced) was able to induce MN in A603-4 (not RIBE-induced). To assess the possible contribution of reactive oxygen species (ROS) or nitric oxide (NO) in medium-mediated RIBE, dimethyl sulfoxide (DMSO; a ROS scavenger) or 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO; an NO scavenger) were added to the medium. A suppressive effect was observed after adding DMSO, but there was no effect after treatment with c-PTIO. These results suggest that an enhanced radiosensitivity may not be directly related to the induction of medium-mediated RIBE. Moreover, ROS are involved in the transduction of the RIBE signal in A. speciosus cells, but NO is not. In conclusion, our results suggest that RIBE may be conserved in wild animals. The results contribute to better knowledge of radiation effects on wild, non-human species. PMID- 29785487 TI - Rapid monitoring of the target protein expression with a fluorescent signal based on a dicistronic construct in Escherichia coli. AB - Real-time quantification of recombinant proteins is important in studies on fermentation engineering, cell engineering, etc. Measurement of the expression level of heterologous proteins in bacterial fermentation broth has traditionally relied on time-consuming and labor-intensive procedures, such as polyacrylamide gel electrophoresis, immunoblot analysis, and biological activity assays. We describe a simple, fast, and high sensitive assay for detecting heterologous proteins production in bacteria either at the overall level (fluorescence spectrophotometry) or at the individual level (fluorescence microscopic image) in this study. Based on a dicistronic model, the translation of target gene in the upstream open reading frame (ORF) was coupled with the synthesis of the mCherry reporter in the downstream ORF in E. coli cells, and subsequently this demonstrated a positive correlation between the expression of target gene and mCherry. Although a time lag exists between the expression of target protein and mCherry reporter, the method described here allows facile monitoring of dynamic changes in target protein expression, relying on indirect determination of the fluorescence intensity of mCherry during fermentation in real-time models. Additionally, the performance of a single bacterial cell factory could be checked under the fluorescence microscope field. PMID- 29785490 TI - Microcirculatory effects of sildenafil in experimental testicular torsion in rats. AB - PURPOSE: Investigate the short-term effect of sildenafil on microcirculation, especially the velocity, the pattern of the flow and the recruitment of the leukocyte in postcapillaries. METHODS: In male Sprague-Dawley rats, the microcirculatory consequences of 60 min experimental testicular torsion, followed by 240 min of reperfusion, were examined. Using fluorescence intravital microscopy, changes in red blood cell velocity in post-capillary venules and rolling as well as adhesion of leukocytes in the postcapillary venules were examined before the torsion and every hour during the reperfusion period. Sildenafil was given 10 min prior to reperfusion (iv 0.7 mg/kg, n = 6), while control animals received saline vehicle (n = 5). RESULTS: The characteristic flow motion disappeared in the affected testicular during the torsion. Red blood cell velocity values were dramatically decreased (by > 50%) and both rolling and adhesion of leukocytes increased during the reperfusion phase. Sildenafil treatment resulted in significantly higher red blood cell velocity values during the entire reperfusion period, but exerted only a temporary positive effect on the plost-ischaemic leukocyte-endothelial interactions. CONCLUSIONS: Intraoperative administration of sildenafil during surgical detorsion may provide marked testicular microperfusion benefits, but failed to influence the overall leukocyte-driven microcirculatory inflammatory reactions. PMID- 29785488 TI - miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF 1alpha via PI3K/AKT pathway. AB - Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by the excessive proliferation of fibroblasts and often considered as a kind of benign skin tumor. microRNA-155 (miR-155) is usually served as a promising marker in antitumor therapy. In view of the similarities of hypertrophic scar and tumor, it is predicted that miR-155 may be a novel therapeutic target in clinical trials. Here we found the expression levels of miR-155 was gradually down regulated and HIF-1alpha was upregulated in HS tissue and HS derived fibroblasts (HFs). And cell proliferation was inhibited when miR-155 was overexpressed or HIF-1alpha was silenced. Moreover, overexpression of miR-155 in HFs could reduce the expression of collagens in vitro and inhibit the collagen fibers arrangement in vivo, whereas miR-155 knockdown gave opposite results. Furthermore, we found that miR 155 directly targeted the HIF-1alpha, which could also independently inhibit the expression of collagens in vitro and obviously improved the appearance and architecture of the rabbit ear scar in vivo when it was silencing. Finally, we found that PI3K/AKT pathway was enrolled in these processes. Together, our results indicated that miR-155 was a critical regulator in the formation and development of hypertrophic scar and might be a potential molecular target for hypertrophic scar therapy. PMID- 29785489 TI - Trpc6 inactivation confers protection in a model of severe nephrosis in rats. AB - : Mutations in canonical transient receptor potential-6 (TRPC6) channels give rise to rare familial forms of focal and segmental glomerulosclerosis (FSGS). Here we examined a possible role for TRPC6 in the progression of chronic puromycin aminonucleoside (PAN) nephrosis in Sprague-Dawley rats, a classic model of acquired nephrotic syndromes. We used CRISPR/Cas9 technology to delete a 239 bp region within exon 2 of the Trpc6 gene (Trpc6del allele). Trpc6del/del rats expressed detectable Trpc6 transcripts missing exon 2, and TRPC6 proteins could be detected by immunoblot of renal cortex. However, the abundance of Trpc6 transcripts and TRPC6 protein in renal cortex was much lower than in Trpc6wt/wt littermates, and functional TRPC6 channels could not be detected in whole-cell recordings from glomerular cells cultured from Trpc6del/del animals, possibly because of disruption of ankyrin repeats 1 and 2. During the chronic phase of PAN nephrosis, Trpc6del/del rats had reduced urine albumin excretion, reduced serum cholesterol and triglycerides, and improved azotemia compared to wild-type Trpc6wt/wt littermates. Glomerulosclerosis was severe during chronic PAN nephrosis in Trpc6wt/wt rats but was markedly reduced in Trpc6del/del littermates. Trpc6del/del animals also had less severe tubulointerstitial fibrosis as assessed by several biochemical and histological analyses, as well as reduced foot process effacement and glomerular basement thickening compared to Trpc6wtt/wt controls. None of the manipulations in this study affected the abundance of TRPC5 channels in renal cortex. TRPC3 was increased in PAN nephrosis and in Trpc6del/del rats. These data support a role for TRPC6 channels in driving an acquired form of secondary FSGS. KEY MESSAGES: We examined aminonucleoside nephrosis in rats with wild type and inactivated TRPC6. TRPC6 channels were inactivated by CRISPR/Cas9 editing of the Trpc6 gene. TRPC6 inactivation reduced albuminuria in the chronic but not the acute phase. TRPC6 inactivation reduced glomerulosclerosis and ultrastructural changes. TRPC6 inactivation also reduced interstitial changes and renal fibrosis. PMID- 29785492 TI - A new prognostic model for localized renal cell carcinoma. PMID- 29785491 TI - Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer? AB - INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. METHODS: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. RESULTS: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. CONCLUSIONS: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options. PMID- 29785494 TI - Spontaneous spinal epidural haematoma mimicking acute ischaemic stroke: case report. PMID- 29785496 TI - Bareback Sexually Explicit Media Consumption and Men Who Have Sex with Men's Responses to Sexual Partners Who Prefer Anal Intercourse With or Without Condoms. AB - This study investigated whether "bareback" (i.e., condomless) sexually explicit media (SEM) consumption is differentially associated with men who have sex with men's (MSM) concerns about, and willingness to have, condomless anal intercourse (CAI) versus anal intercourse with condoms. Participants were 659 Australian MSM who all reported their bareback SEM consumption and read a vignette in which they were propositioned for sex by a hypothetical male target. Participants were randomly assigned to one of four vignettes, in which the target exclusively preferred either CAI or anal intercourse with condoms, and either did or did not disclose that they took pre-exposure prophylaxis (PrEP). Perceived partner attractiveness was also measured as a potential moderator. Greater bareback SEM consumption was associated with reduced concerns about, and intentions to have, sex with a target who exclusively preferred CAI. Bareback SEM consumption, however, was not related to concerns about, or intentions to have, sex with a target who exclusively preferred anal intercourse with condoms. PrEP disclosure was not causally related to either concern about having, or intentions to have, sex with the target, nor did it moderate the relationship between bareback SEM consumption and these outcomes. Perceived partner attractiveness moderated the effect of bareback SEM consumption on general sexual intentions, such that bareback SEM was only associated with greater intentions to have sex when the partner was perceived to be highly attractive. PMID- 29785495 TI - D-Lactate and intestinal fatty acid-binding protein are elevated in serum in patients with acute ischemic stroke. AB - Experimental studies suggest that the intestinal barrier is affected in ischemic stroke. D-Lactate and intestinal fatty acid-binding protein (IFABP) are markers of intestinal mucosa integrity and barrier function. Our purpose was to evaluate the serum concentrations of these markers in patients with acute ischemic stroke (AIS). We included patients with AIS and used healthy subjects as controls. Clinical, demographic and outcome measures were recorded. Blood was drawn within 24 h of symptom onset. Serum concentrations of D-Lactate and IFABP were determined using commercially available colorimetric and ELISA kits, respectively. We included a total of 61 patients (median age of 64 years). The majority of patients were male (57.4%). The most common cause of stroke was atherosclerosis (34.4%), followed by small-vessel disease and cardioembolic (32.7% each). Mean admission NIHSS score was 8. Median IFABP and D-Lactate concentrations were significantly higher in patients than in controls. Concentrations were not associated with stroke severity or 3-month outcome. Patients with large-artery atherosclerosis and cardioembolic etiology had higher D-Lactate values than patients with small-vessel disease. D-Lactate and IFABP were significantly elevated in patients with AIS. This suggests that there is disruption of the intestinal barrier in patients with AIS. PMID- 29785493 TI - Mindset and Communication Barriers in the Diffusion of Bariatric Surgery. AB - PURPOSE OF REVIEW: Cumulating evidence is available to demonstrate the efficacy of bariatric surgery (BS) in achieving weight loss and optimizing comorbidities. However, currently, only a minority of eligible patients approaches bariatric centers. The underuse of BS can no longer be explained by the lack of evidence supporting its beneficial outcomes along with its favorable safety-profile, rather, by the supporting infrastructure, insurance coverage, and mindset of society, including potential patients and allied healthcare professionals. As a framework to approach mindset barriers in the diffusion of BS, we used the Rogers' levels of the innovation adoption process: (1) knowledge, (2) persuasion, (3) decision, (4) implementation, and (5) confirmation. RECENT FINDINGS: Knowledge: people tend to believe that obesity is a result of lack of willpower and they have difficulties in differentiating BS from cosmetic surgery. Eligible patients often do not assess themselves as being morbidly obese and are unaware that they would qualify for BS. Persuasion: majority of BS candidates search health information online, with the aim of getting information about surgical techniques and other patients' experiences. Decision: metabolically more compromised patients are more likely to opt for BS. IMPLEMENTATION: general practitioners who already referred patients for BS seem to be more confident to refer again, to tackle obesity and manage postoperative follow-up. Confirmation: postbariatric patients seem to be more self-confident and more productive at work; however, their stigmatization might prevail related to the way they have achieved weight loss. Dissemination of balanced and corroborative information seems to be the main instrument to combat mindset barriers. The integration of general practitioners under the umbrella of bariatric centers has a great potential to increase referrals. Social media may represent a helpful tool to be used by medical professionals and patient-role models to improve confident decision-making of bariatric candidates. PMID- 29785497 TI - Crystal structure of Arabidopsis thaliana glutamyl-tRNAGlu reductase in complex with NADPH and glutamyl-tRNAGlu reductase binding protein. AB - In higher plants, the tetrapyrrole biosynthesis pathway starts from the reaction catalyzed by the rate-limiting enzyme, glutamyl-tRNAGlu reductase (GTR). In Arabidopsis thaliana, GTR is controlled by post-transcriptional regulators such as GTR binding protein (GBP), which stimulates AtGTR activity. The NADPH-binding domain of AtGTR undergoes a substantial movement upon GBP binding. Here, we report the crystal structure of AtGTR-NADPH-GBP ternary complex. NADPH binding causes slight structural changes compared with the AtGTR-GBP binary complex, and possibly take a part of the space needed by the substrate glutamyl-tRNAGlu. The highly reactive sulfhydryl group of the active-site residue Cys144 shows an obvious rotation, which may facilitate the hydride transfer from NADPH to the thioester intermediate to form glutamate-1-semialdehyde. Furthermore, Lys271, Lys274, Ser275, Asn278, and Gln282 of GBP participate in the interaction between AtGTR and GBP, and the stimulating effect of GBP decreased when all of these residues were mutated to Ala. When the Cys144 of AtGTR was mutated to Ser, AtGTR activity could not be detected even in the presence of GBP. PMID- 29785498 TI - Survival of Planktonic and Sessile Cells of Lactobacillus rhamnosus and Lactobacillus reuteri upon Exposure to Simulated Fasting-State Gastrointestinal Conditions. AB - In this study, we report on the formation and resilience of Lactobacillus reuteri HFI-LD5 and Lactobacillus rhamnosus HFI-K2 biofilms cultivated in a CO2 evolution measurement system (CEMS) and exposed to biologically relevant, fasting-state gastrointestinal fluids under continuous flow conditions. For comparative purposes, planktonic and sessile populations of L. reuteri HFI-LD5 and L. rhamnosus HFI-K2 were each exposed to fasting-state gastric fluid (FSGF, pH 2.0) for 2 h, fasting-state intestinal fluid (FSIF, pH 7.5) for 6 h, and simulated colonic fluid (SCoF, pH 7.0) for 24 h. Planktonic cell numbers of L. reuteri HFI LD5 declined from 6.6 log10 CFU/mL to 3.2 log10 CFU/mL and L. rhamnosus HFI-K2 from 6.6 log10 CFU/mL to undetectable levels after exposure to FSGF. Limited loss in viability was observed when free-floating cells were exposed to FSIF and SCoF. Sessile populations of both strains survived and recovered from the sequential exposure to all three gastric fluids despite observed detachment of biofilm biomass and a temporary decrease in metabolic activity to below detection limits, as recorded by changes in whole-biofilm CO2 production rates. The planktonic cell focused gut microbiome-related research has most likely caused an underestimation in the overall survival ability of microorganisms in the gastrointestinal tract. Sessile cells of L. reuteri HFI-LD5 were metabolically inactive when exposed to gastric (FSGF) and intestinal (FSIF) fluids, suggesting that biofilms are formed in the small intestinal tract as survival mechanism. In the case of L. rhamnosus HFI-K2, cells were released from biofilms when suddenly exposed to pH 2.0. PMID- 29785500 TI - Boosting the efficiency of site-saturation mutagenesis for a difficult-to randomize gene by a two-step PCR strategy. AB - Site-saturation mutagenesis (SSM) has been used in directed evolution of proteins for a long time. As a special form of saturation mutagenesis, it involves individual randomization at a given residue with formation of all 19 amino acids. To date, the most efficient embodiment of SSM is a one-step PCR-based approach using NNK codon degeneracy. However, in the case of difficult-to-randomize genes, SSM may not deliver all of the expected 19 mutants, which compels the user to invest further efforts by applying site-directed mutagenesis for the construction of the missing mutants. To solve this problem, we developed a two-step PCR-based technique in which a mutagenic primer and a non-mutagenic (silent) primer are used to generate a short DNA fragment, which is recovered and then employed as a megaprimer to amplify the whole plasmid. The present two-step and older one-step (partially overlapped primer approach) procedures were compared by utilizing cytochrome P450-BM3, which is a "difficult-to-randomize" gene. The results document the distinct superiority of the new method by checking the library quality on DNA level based on massive sequence data, but also at amino acid level. Various future applications in biotechnology can be expected, including the utilization when constructing mutability landscapes, which provide semi rational information for identifying hot spots for protein engineering and directed evolution. PMID- 29785501 TI - Improving the acetic acid tolerance and fermentation of Acetobacter pasteurianus by nucleotide excision repair protein UvrA. AB - Acetic acid bacteria (AAB) are widely used in acetic acid fermentation due to their remarkable ability to oxidize ethanol and high tolerance against acetic acid. In Acetobacter pasteurianus, nucleotide excision repair protein UvrA was up regulated 2.1 times by acetic acid when compared with that without acetic acid. To study the effects of UvrA on A. pasteurianus acetic acid tolerance, uvrA knockout strain AC2005-DeltauvrA, uvrA overexpression strain AC2005 (pMV24-uvrA), and the control strain AC2005 (pMV24), were constructed. One percent initial acetic acid was almost lethal to AC2005-DeltauvrA. However, the biomass of the UvrA overexpression strain was higher than that of the control under acetic acid concentrations. After 6% acetic acid shock for 20 and 40 min, the survival ratios of AC2005 (pMV24-uvrA) were 2 and 0.12%, respectively; however, they were 1.5 and 0.06% for the control strain AC2005 (pMV24). UvrA overexpression enhanced the acetification rate by 21.7% when compared with the control. The enzymes involved in ethanol oxidation and acetic acid tolerance were up-regulated during acetic acid fermentation due to the overexpression of UvrA. Therefore, in A. pasteurianus, UvrA could be induced by acetic acid and is related with the acetic acid tolerance by protecting the genome against acetic acid to ensure the protein expression and metabolism. PMID- 29785502 TI - Comparative persistence of human sewage-specific enterococcal bacteriophages in freshwater and seawater. AB - Enterococcus faecalis bacteria have been recently reported for their ability to host bacteriophages that are specifically from human sewage, suggesting their application to track human fecal contamination in water resources. However, little is known about the survivability of sewage-specific enterococcal bacteriophages in various water matrices under ambient and storage conditions. In this study, bacteriophages that were derived from the Thailand-isolated E. faecalis strains AIM06 and SR14 exhibited morphologies consistent with the Siphoviridae, Podoviridae, and Myoviridae families. Four representative bacteriophages were separately spiked into environmental water samples (n = 7) comprising freshwater and seawater with low- and high-pollution (LF, HF, LS, and HS, respectively) levels, defined according to Thailand Water Quality Standards. All bacteriophages decayed fastest in HS or HF samples at 30 degrees C, reaching a 5-log10 reduction in 2.2 to 9.8 days, and slowest in LS samples, requiring 8.8 to 23.5 days. The decay rates were 5 to 53 times lower at a storage temperature of 5 degrees C. HF samples could be stored for as little as 2.5 days to prevent the decay of 50% of the phages. Myoviridae phages decayed faster than Siphoviridae phages and Podoviridae phages in most water matrices at 30 degrees C. Moreover, the decay rates were 1.8 to 92 times slower in filtered samples, emphasizing a strong role for water constituents, i.e., suspended solids and natural microorganisms, in phage persistence. This study emphasized that differential enterococcal bacteriophage persistence should be considered when planning the monitoring and interpreting of fecal sources by microbial source tracking. PMID- 29785499 TI - On the current role of hydratases in biocatalysis. AB - Water addition to carbon-carbon double bonds provides access to value-added products from inexpensive organic feedstock. This interesting but relatively little-studied reaction is catalysed by hydratases in a highly regio- and enantiospecific fashion with excellent atom economy. Considering that asymmetric hydration of (non-activated) carbon-carbon double bonds is virtually impossible with current organic chemistry, enzymatic hydration reactions are highly attractive for industrial applications. Hydratases have been known for several decades but their biocatalytic potential has only been explored over the past 15 years. As a result, a considerable amount of information on this enzyme group has become available, enabling their development for practical applications. This review focuses on hydratases catalysing water addition to non-activated carbon carbon double bonds, and examines hydratases from a biochemical, structural and mechanistic angle. Current challenges and opportunities in hydration biocatalysis are discussed, and, ultimately, their potential for organic synthesis is highlighted. PMID- 29785503 TI - Prolonged forearm ischemia attenuates endothelium-dependent vasodilatation and plasma nitric oxide metabolites in overweight middle-aged men. AB - PURPOSE: Repeated cycles of endothelial ischemia-reperfusion injury and the resulting respiratory burst contribute to the irreversible pathophysiology of vascular diseases, and yet, the effects of ischemia reperfusion on vascular function, oxidative stress, and nitric oxide (NO) bioavailability have not been assessed simultaneously. Therefore, this study sought to examine the effects of prolonged forearm occlusion and subsequent reperfusion on NO-dependent brachial artery endothelial function. METHODS: Flow-mediated dilatation was measured at baseline and 15, 30, and 45 min after 20-min forearm occlusion in 14 healthy, but physically inactive middle-aged men (53.7 +/- 1.2 years, BMI: 28.1 +/- 0.1 kg m 2). Venous blood samples collected from the occluded arm were analyzed for NO metabolites and markers of oxidative stress. RESULTS: FMD was significantly depressed after the prolonged occlusion compared to baseline, with a significant reduction 15-min post-occlusion (6.6 +/- 0.7 to 2.9 +/- 0.4%, p < 0.001); FMD remained depressed after 30 min (4.1 +/- 0.6%, p = 0.001), but was not significantly different to baseline after 45-min recovery (5.4 +/- 0.7%, p = 0.079). Plasma nitrate (main time effect: p = 0.015) and nitrite (main time effect: p = 0.034) concentrations were significantly reduced after prolonged occlusion. Plasma catalase activity was significantly elevated at 4- (p = 0.016) and 45-min (p = 0.001) post-occlusion, but plasma peroxiredoxin 2 and protein carbonyl content did not change. CONCLUSIONS: Prolonged forearm occlusion resulted in acute impairment of endothelium-dependent vasodilatation of the brachial artery for at least 30 min after reperfusion. We demonstrate that this vascular dysfunction is associated with oxidative stress and reduced NO bioavailability following reperfusion. PMID- 29785504 TI - Impact of a VAP bundle in Belgian intensive care units. AB - BACKGROUND: In order to decrease the incidence of ventilator-associated pneumonia (VAP) in Belgium, a national campaign for implementing a VAP bundle involving assessment of sedation, cuff pressure control, oral care with chlorhexidine and semirecumbent position, was launched in 2011-2012. This report will document the impact of this campaign. METHODS: On 1 day, once a year from 2010 till 2016, except in 2012, Belgian ICUs were questioned about their ventilated patients. For each of these, data about the application of the bundle and the possible treatment for VAP were recorded. RESULTS: Between 36.6 and 54.8% of the 120 Belgian ICUs participated in the successive surveys. While the characteristics of ventilated patients remained similar throughout the years, the percentage of ventilated patients and especially the duration of ventilation significantly decreased before and after the national VAP bundle campaign. Ventilator care also profoundly changed: Controlling cuff pressure, head positioning above 30 degrees were obtained in more than 90% of cases. Oral care was more frequently performed within a day, using more concentrated solutions of chlorhexidine. Subglottic suctioning also was used but in only 24.7% of the cases in the last years. Regarding the prevalence of VAP, it significantly decreased from 28% of ventilated patients in 2010 to 10.1% in 2016 (p <= 0.0001). CONCLUSION: Although a causal relationship cannot be inferred from these data, the successive surveys revealed a potential impact of the VAP bundle campaign on both the respiratory care of ventilated patients and the prevalence of VAP in Belgian ICUs encouraging them to follow the guidelines. PMID- 29785505 TI - Preparing for an "Insured" Old Age: Insurance Purchase and Self-Support in Old Age in Rural China. AB - This article explores an emerging trend among young and middle-aged rural couples in Northeast China who have purchased recently marketized commercial insurance as a way to prepare for self-support in old age. It discusses how the commercial insurance industry has created a rural elder-care market among a population that traditionally relied on family for support in old age. It also delves into the ways in which the transformations of intergenerational exchange and family structure and a lack of health care access have contributed to the preparation for self-support in old age and have thus fostered the creation of a rural elder care market for the insurance industry. This emerging trend reveals a transition from traditional family support to a combination of multiple ways of elder care, in particular self-support in old age. It also suggests that while the Chinese state is facing a pressing issue of supporting an increasing aging population and the Chinese family is coping with the burden of elder care, the insurance industry is playing an increasing role in elder care in China. PMID- 29785506 TI - Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report. AB - Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies. PMID- 29785507 TI - Assessing Mortality Models in Systemic Sclerosis-Related Interstitial Lung Disease. AB - PURPOSE: The gender, age, and lung physiology (GAP) model, interstitial lung diseases-GAP (ILD-GAP) model, and the smoking history, age, and diffusion capacity of the lung (SADL) model were compared using a systemic sclerosis-ILD (SSc-ILD) cohort to evaluate which best determined prognosis. METHODS: The models were applied to a cohort of 179 patients with SSc seen at a tertiary care center within 1 year of ILD diagnosis. Demographics, clinical characteristics, and mortality were recorded. The performance of the models was assessed using standardized mortality ratios (SMR) of observed versus predicted outcomes for calibration and concordance (c)-statistics for discrimination. RESULTS: SSc-ILD patients with usual interstitial pneumonia (31, 17%) had a higher mortality than those with non-specific interstitial pneumonia (147, 83%) (hazard ratio 2.27; 95%CI 1.03-4.97). All 3 models had comparable discrimination (c = 0.72, 0.72, and 0.71, respectively). Regarding calibration, the ILD-GAP model underestimated mortality (SMR 1.50; 95%CI 1.05-2.14). Calibration was acceptable for SADL (SMR 1.00; 95%CI 0.70-1.44) and GAP (SMR 0.90; 95%CI 0.63-1.29). The SADL model underestimated mortality in Stage I ILD. CONCLUSIONS: The ILD-GAP model underestimated mortality, and the SADL model underestimated mortality in certain subgroups. However, the GAP model performed well in this cohort, providing the best prognostic information for SSc-ILD. PMID- 29785508 TI - Lacosamide: A Review in Focal-Onset Seizures in Patients with Epilepsy. AB - Lacosamide (Vimpat(r)) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged >= 4 years with epilepsy. In adults and adolescents (aged >= 16 years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18 weeks) treatment, with efficacy sustained over the longer-term (up to 8 years). Moreover, patients were effectively switched from adjunctive oral lacosamide to the same dosage of intravenous lacosamide. Oral lacosamide was an effective conversion to monotherapy agent in this patient population and as monotherapy demonstrated noninferiority to carbamazepine controlled release in terms of seizure freedom. Antiepileptic benefits were maintained during longer term (<= 2 years) monotherapy. The antiepileptic efficacy of lacosamide in children aged >= 4 years has been extrapolated from data from adults and adolescents, with a similar response expected provided paediatric dosage adaptations are used and safety is demonstrated. Indeed, preliminary data demonstrated the efficacy of short-term (16 weeks) adjunctive lacosamide in patients aged >= 4 to < 17 years. Oral lacosamide was generally well tolerated over the short- and longer-term when administered as adjunctive therapy, a conversion to monotherapy agent and monotherapy in adults and adolescents and when administered as adjunctive therapy in children aged >= 4 years. Thus, lacosamide is a useful option for the management of focal-onset seizures across a broad age range, starting as early as 4 years of age. PMID- 29785509 TI - Why, so far, have epidemics always eventually petered out? Quasispecies theory suggests a (testable!) answer. AB - In this paper, it is argued that the fact that, so far, even the worst and most far-reaching epidemics-from the Plague of Athens in 430 BC and the Plague of Justinian in 541/542 AD to the Hong Kong Flu from 1968/69-always finally petered out can be explained using Manfred Eigen's quasispecies concept: Indeed, as the infectious agents, while duplicating themselves in the infected organisms, mutate all the time, these infected organisms carry along quite a multitude of mutational variants or-in Manfred Eigen's terms-a whole quasispecies of infectious agents implying that, within that quasispecies, those variants that differ from the wild type may actually serve as some kind of vaccination program when infecting some previously uninfected persons. In this context, some data regarding various recent epidemics will also be illustrated, using Daniel Huson's SplitsTree software tool. PMID- 29785510 TI - Measuring translational diffusion of 15N-enriched biomolecules in complex solutions with a simplified 1H-15N HMQC-filtered BEST sequence. AB - Pulsed-field gradient nuclear magnetic resonance has seen an increase in applications spanning a broad range of disciplines where molecular translational diffusion properties are of interest. The current study introduces and experimentally evaluates the measurement of translational diffusion coefficients of 15N-enriched biomolecules using a 1H-15N HMQC-filtered band-selective excitation short transient (BEST) sequence as an alternative to the previously described SOFAST-XSTE sequence. The results demonstrate that accurate translational diffusion coefficients of 15N-labelled peptides and proteins can be obtained using this alternative 1H-15N HMQC-filtered BEST sequence which is implementable on NMR spectrometers equipped with probes fitted with a single-axis field gradient, including most cryoprobes dedicated to bio-NMR. The sequence is of potential use for direct quantification of protein or peptide translational diffusion within complex systems, such as in mixtures of macromolecules, crowded solutions, membrane-mimicking media and in bicontinuous cubic phases, where conventional sequences may not be readily applicable due to the presence of intense signals arising from sources other than the protein or peptide under investigation. PMID- 29785511 TI - Lamellar macular holes: surgical outcome of 106 patients with long-term follow up. AB - PURPOSE: To determine long-term results of vitrectomy for lamellar macular holes (LMH). To evaluate how the type of lamellar macular hole (tractional vs. degenerative) and the crystalline lens status might influence visual outcomes. METHODS: We collected data from 106 patients with symptomatic lamellar macular hole that underwent pars plana vitrectomy with membranectomy and internal limiting membrane peeling. Best-corrected visual acuity (BCVA) and optical coherence tomography appearance were determined preoperatively and postoperatively. RESULTS: Most of the lamellar holes were of tractional type (65%). Mean follow-up after surgery was 36 months. Mean BCVA increased from 20/50 to 20/43 at 6 months and 20/33 at last follow-up visit (p < 0.001). Vision improved in 74 (70%), remained stable in 11 (10%), and decreased in 21 (20%) eyes. Subgroup analysis showed that visual acuity significantly increased in the tractional but not in the degenerative forms of LMH. Thirteen eyes lost two or more ETDRS lines after surgery. Preoperative phakic/pseudophakic status influenced the functional outcomes. CONCLUSIONS: Surgery may be effective in some subsets of patients with lamellar macular hole, but postoperative visual loss is not uncommon and prospective controlled studies are warranted. PMID- 29785512 TI - Efficacy of Sports Club Activities on Exercise Tolerance Among Japanese Middle and High School Children and Adolescents After Fontan Procedure. AB - The exercise tolerance of Fontan patients is poorer than that of healthy people. Some previous studies reported that exercise tolerance can be improved in this population by cardiac rehabilitation. This study aimed to determine the factors associated with peak oxygen uptake (VO2) and to subsequently clarify the correlation between participation in sports club activities and variables related to exercise tolerance. Cardiopulmonary exercise tests were performed by 115 Fontan patients aged between 6 and 20 years. The patients completed questionnaires on their daily physical activities including participation in extracurricular sports clubs in middle (junior high school) and high school. Peak VO2 had a significant negative correlation with age and a positive correlation with hemoglobin, stroke volume, and resting tidal volume in the entire study group. Additionally, the sports club participants who were middle and high school students had significantly higher peak VO2 and resting tidal volume. Exercise habits including participation in sports club activities may promote exercise tolerance by improving respiratory function in Fontan adolescents. PMID- 29785513 TI - Jdpd: an open java simulation kernel for molecular fragment dissipative particle dynamics. AB - Jdpd is an open Java simulation kernel for Molecular Fragment Dissipative Particle Dynamics with parallelizable force calculation, efficient caching options and fast property calculations. It is characterized by an interface and factory-pattern driven design for simple code changes and may help to avoid problems of polyglot programming. Detailed input/output communication, parallelization and process control as well as internal logging capabilities for debugging purposes are supported. The new kernel may be utilized in different simulation environments ranging from flexible scripting solutions up to fully integrated "all-in-one" simulation systems. PMID- 29785515 TI - Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer. AB - PURPOSE: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223RaCl2) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18F-labeled sodium fluoride PET/CT. METHODS: We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29.7) receiving 223RaCl2. Overall survival (OS) and progression-free survival (PFS), estimated by the Kaplan-Meier method and compared using a log-rank test, were evaluated for patient groups corresponding to different definitions of PSA flare. Metabolic 18F-fluoride PET/CT data were analyzed as well. RESULTS: Immediate PSA decline was observed in 49 patients (29.2%), whereas no PSA response was observed in 59 patients (35.1%). PSA flare (defined as rise after the first cycle followed by decrease below the baseline) was observed in 20 patients (11.9%) and PSA flare followed by a decrease from peak but not below baseline was observed in 40 (23.8%). The first flare subgroup had a median PFS and OS of 20.8 and 23.9 months, respectively. These outcomes were not significantly different from patients with immediate PSA decrease, but were significantly better than in patients with persistent PSA elevation (3.1 months for PFS and 11.5 months for OS, p < 0.001). Moreover, the PSA flare group showed an alkaline phosphatase (ALP) decrease significantly greater than non-responders (p = 0.003). Metabolic 18F-fluoride PET/CT data were available in 35 patients at baseline and during 233RaCl2 therapy. The tumor burden reduction, expressed by DeltaTLF10 and DeltaFTV10, was more evident within PSA flare group below baseline than non responders (p = 0.005 and 0.001, respectively). CONCLUSIONS: This report suggests that a flare does not necessarily indicate lack of response to 223RaCl2 therapy. PMID- 29785514 TI - Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning. AB - PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 90Y-labelled and 177Lu labelled peptides is an effective strategy for the treatment of metastatic/nonresectable neuroendocrine tumours (NETs). Dosimetry provides important information useful for optimizing PRRT with individualized regimens to reduce toxicity and increase tumour responses. However, this strategy is not applied in routine clinical practice, despite the fact that several dosimetric studies have demonstrated significant dose-effect correlations for normal organ toxicity and tumour response that can better guide therapy planning. The present study reviews the key relationships and the radiobiological models available in the literature with the aim of providing evidence that optimization of PRRT is feasible through the implementation of dosimetry. METHODS: The MEDLINE database was searched combining specific keywords. Original studies published in the English language reporting dose-effect outcomes in patients treated with PRRT were chosen. RESULTS: Nine of 126 studies were selected from PubMed, and a further five were added manually, reporting on 590 patients. The studies were analysed and are discussed in terms of weak and strong elements of correlations. CONCLUSION: Several studies provided evidence of clinical benefit from the implementation of dosimetry in PRRT, indicating the potential contribution of this approach to reducing severe toxicity and/or reducing undertreatment that commonly occurs. Prospective trials, possibly multicentre, with larger numbers of patients undergoing quantitative dosimetry and with standardized methodologies should be carried out to definitively provide robust predictive paradigms to establish effective tailored PRRT. PMID- 29785516 TI - Increased water temperature altered hemato-biochemical parameters and structure of peripheral erythrocytes in striped catfish Pangasianodon hypophthalmus. AB - The increase of water temperature due to global warming is a great concern of aquaculturists and fishery biologists. In the present study, we examined the effects of high temperature on hematological parameters and blood glucose levels in striped catfish, Pangasianodon hypophthalmus exposed to three temperature conditions (28, 32, and 36 degrees C) for 7 days. Fish were sacrificed at days 1, 3, and 7. Erythroblasts (Ebs), erythrocytic cellular abnormalities (ECA), and erythrocytic nuclear abnormalities (ENA) were assayed using peripheral erythrocytes of the sampled fishes. Hemoglobin (Hb) and red blood cell (RBC) significantly (P < 0.05) decreased at 36 degrees C after 3 and 7 days of exposure, whereas white blood cell (WBC) showed opposite scenario. Blood glucose levels significantly (P < 0.05) increased at 36 degrees C on day 3. Frequencies of Ebs, ECA, and ENA were found to be elevated at increased temperature. Differential leucocytes count showed significant increases in neutrophil and decreases in lymphocytes in the highest temperature (36 degrees C). Dissolved oxygen decreased and free CO2 increased significantly (P < 0.05) with increasing temperature, while the pH and total alkalinity of the water were almost unchanged throughout the study period. Therefore, the present study demonstrated that striped catfish feel better adaptation at 28 and 32 degrees C, while high temperature 36 degrees C is likely stressful to this fish species. PMID- 29785517 TI - Optimization and enhancement of textile reactive Remazol black B decolorization and detoxification by environmentally isolated pH tolerant Pseudomonas aeruginosa KY284155. AB - Azo dyes are complex derivatives of diazene used in food and textile manufacture. They are highly recalcitrant compounds, and account for severe environmental and health problems. Different strains of Pseudomonas species were isolated from textile wastewater effluents. The bioconversion of Remazol black B (a commonly used water soluble dye) by Pseudomonas aeruginosa was observed in static conditions. The bio-decolorization process was optimized by a multi factorial Plackett-Burman experimental design. Decolorization of 200 mg L-1 reached 100% in 32 h. Interestingly, the presence of yeast extract, magnesium and iron in the culture media, highly accelerated the rate of decolorization. Moreover, one of our isolates, P. aeruginosa KY284155, was kept high degradation rates at high pH (pH = 9), which represents the pH of most textile wastewater effluents, and was able to tolerate high concentration of dye up to 500 mg L-1. In bacteria, azo-dye degradation is often initiated by reductive azo compound cleavage catalyzed by azo-reductases. Three genes encoding azo-reductases, paazoR1, paazoR2 and paazoR3, could be identified in the genome of the isolated P. aeruginosa stain (B1). Bioinformatics analyses of the paazoR1, paazoR2 and paazoR3 genes reveal their prevalence and conservation in other P. aeruginosa strains. Chemical oxygen demand dramatically decreased and phyto-detoxification of the azo dye was accomplished by photocatalytic post treatment of the biodegradation products. We suggest applying combined biological photocatalytic post treatment for azo dyes on large scale, for effective, cheap decolorization and detoxification of azo dyes, rendering them safe enough to be discharged in the environment. PMID- 29785520 TI - Times from Infection to Disease-Induced Death and their Influence on Final Population Sizes After Epidemic Outbreaks. AB - For epidemic models, it is shown that fatal infectious diseases cannot drive the host population into extinction if the incidence function is upper density dependent. This finding holds even if a latency period is included and the time from infection to disease-induced death has an arbitrary length distribution. However, if the incidence function is also lower density-dependent, very infectious diseases can lead to a drastic decline of the host population. Further, the final population size after an epidemic outbreak can possibly be substantially affected by the infection-age distribution of the initial infectives if the life expectations of infected individuals are an unbounded function of infection age (time since infection). This is the case for lognormal distributions, which fit data from infection experiments involving tiger salamander larvae and ranavirus better than gamma distributions and Weibull distributions. PMID- 29785519 TI - Threshold Dynamics of a Temperature-Dependent Stage-Structured Mosquito Population Model with Nested Delays. AB - Mosquito-borne diseases remain a significant threat to public health and economics. Since mosquitoes are quite sensitive to temperature, global warming may not only worsen the disease transmission case in current endemic areas but also facilitate mosquito population together with pathogens to establish in new regions. Therefore, understanding mosquito population dynamics under the impact of temperature is considerably important for making disease control policies. In this paper, we develop a stage-structured mosquito population model in the environment of a temperature-controlled experiment. The model turns out to be a system of periodic delay differential equations with periodic delays. We show that the basic reproduction number is a threshold parameter which determines whether the mosquito population goes to extinction or remains persistent. We then estimate the parameter values for Aedes aegypti, the mosquito that transmits dengue virus. We verify the analytic result by numerical simulations with the temperature data of Colombo, Sri Lanka where a dengue outbreak occurred in 2017. PMID- 29785518 TI - Fumarylacetoacetate hydrolase is involved in salt stress response in Arabidopsis. AB - MAIN CONCLUSION: Fumarylacetoacetate hydrolase participates in positive regulation of salt stress in Arabidopsis. Fumarylacetoacetate hydrolase (FAH) catalyzes the hydrolysis of fumarylacetoacetate into fumarate and acetoacetate, the final step in the Tyr degradation pathway that is essential to animals. However, the Tyr degradation pathway is not well understood in plants. Previously, we found that mutation of the SHORT-DAY SENSITIVE CELL DEATH 1 (SSCD1) gene encoding FAH in Arabidopsis causes spontaneous cell death under short day, which first indicated that the Tyr degradation pathway also plays an important role in plants. In this study, we found that the SSCD1 gene was up regulated by salt stress, and the sscd1 mutant was hypersensitive to salt stress. However, the double mutant of SSCD1 and HOMOGENTISATE DIOXYGENASE, in which intermediates of the Tyr degradation pathway could not be produced, displayed a normal response to salt stress. Furthermore, the sscd1 mutant showed more accumulation of reactive oxygen species (ROS) and less up-regulation of some ROS scavenging genes such as ASCORBATE PEROXIDASE 2 and COPPER/ZINC SUPEROXIDE DISMUTASE 1 compared with wild type under salt stress. In addition, SSCD1 expression was also up-regulated by H2O2, and the sscd1 mutant exhibited hypersensitivity to oxidative stress compared with wild type. Taken together, we concluded that loss of FAH in sscd1 leads to the accumulation of Tyr degradation intermediates, which impairs the up-regulation of some ROS-scavenging genes under salt stress, causing more accumulation of ROS, resulting in the hypersensitivity of sscd1 to salt stress. PMID- 29785521 TI - Spatial Stochastic Intracellular Kinetics: A Review of Modelling Approaches. AB - Models of chemical kinetics that incorporate both stochasticity and diffusion are an increasingly common tool for studying biology. The variety of competing models is vast, but two stand out by virtue of their popularity: the reaction-diffusion master equation and Brownian dynamics. In this review, we critically address a number of open questions surrounding these models: How can they be justified physically? How do they relate to each other? How do they fit into the wider landscape of chemical models, ranging from the rate equations to molecular dynamics? This review assumes no prior knowledge of modelling chemical kinetics and should be accessible to a wide range of readers. PMID- 29785522 TI - Non-invasive vagus nerve stimulation significantly improves quality of life in patients with persistent postural-perceptual dizziness. AB - Persistent postural-perceptual dizziness (PPPD) is one of the most common causes of chronic vestibular disorders, with a substantial portion of the affected patients showing no significant improvement to standard therapies (i.e., pharmacotherapy, behavioral psychotherapy). Patients with PPPD have been shown to have a significant comorbidity with anxiety disorders and depression. Further, these patients show an activation of the autonomic nervous system resulting in symptoms such as nausea, increase of heart rate, and sweating. Based on the comorbidities and the activation of the autonomic nervous system, we addressed the question whether non-invasive vagus nerve stimulation (nVNS) might be a treatment option for these patients. In this prospective study we, therefore, applied nVNS to patients with treatment-refractory (to the standard therapy) PPPD. The stimulation protocol was similar to previous studies in patients with cluster headache and consisted of stimulations during exacerbations or acute attacks of vertigo, but also with regular stimulations in the morning and evening as prophylactic treatment. Results showed that non-invasive vagus nerve stimulation significantly improved quality of life, as measured by the EQ-5D-3L (p = 0.04), and depression, as measured by the HADS-D (p = 0.002), in the nVNS group, but not in the age- and sex-matched group with standard of care (SOC) treatment. Moreover, in the pooled analysis (additional 4 weeks of stimulation also in the SOC-group), less severe vertigo attacks/exacerbations (p = 0.04), a decrease in total postural sway path as measured by posturography (p = 0.02), as well as tendentious less anxiety (p = 0.08), occurred after stimulation. These data imply that short term nVNS is a safe and promising treatment option in patients with otherwise refractory PPPD. PMID- 29785525 TI - Beyond the Border and Into the Heartland: Spatial Patterning of U.S. Immigration Detention. AB - The expansion of U.S. immigration enforcement from the borders into the interior of the country and the fivefold increase in immigration detentions and deportations since 1995 raise important questions about how the enforcement of immigration law is spatially patterned across American communities. Focusing on the practice of immigration detention, the present study analyzes the records of all 717,160 noncitizens detained by Immigration and Customs Enforcement (ICE) in 2008 and 2009-a period when interior enforcement was at its peak-to estimate states' detention rates and examine geographic variation in detention outcomes, net of individual characteristics. Findings reveal substantial state heterogeneity in immigration detention rates, which range from approximately 350 detentions per 100,000 noncitizens in Connecticut to more than 6,700 detentions per 100,000 noncitizens in Wyoming. After detainment, individuals' detention outcomes are geographically stratified, especially for detainees eligible for pretrial release. These disparities indicate the important role that geography plays in shaping individuals' chances of experiencing immigration detention and deportation. PMID- 29785523 TI - Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study. AB - INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment. The annualized relapse rate (ARR) the year before rituximab was 0.86, 53.3% of patients had gadolinium enhanced lesion, and mean Expanded Disability Status Scale (EDSS) had increased from 4.2 to 4.9. During treatment, the ARR was reduced an 88.4% (p < 0.001). A significant decrease of EDSS to 4.6 was observed (p = 0.01) after 1 year of treatment, which remained stable during the second year in both groups. There was no evidence of disease activity in 70% of total sample, 74.2% of RRMS, and 67% of the PMS patients. Infusion-related symptoms were the most prevalent side effect (18.8%) and most were mild. Three thrombotic events were detected. CONCLUSION: Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment. PMID- 29785524 TI - A 9-year follow-up study of quantitative muscle strength changes in myotonic dystrophy type 1. AB - Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder presenting with major muscle impairments. However, few studies have addressed muscle strength progression using quantitative methods. The aims of this study were to document muscle strength changes in eight muscle groups among adults with DM1 over a 9 year period, and to compare this progression between phenotypes (adult and late onset) and sex. Patients with a genetic diagnosis of DM1 with the late-onset or the adult phenotype were recruited at baseline through the clinical registry of the Saguenay Neuromuscular Clinic. The maximum isometric muscle strength was measured at baseline and 9 years later using a standardized protocol of quantitative muscle testing. Muscle groups included were shoulder abductors, elbow flexors/extensors, wrist extensors, hip flexors, knee flexors/extensors, and ankle dorsiflexors. For the whole group, a mean loss of 24.5-52.8% was observed over the 9-year period for all muscle groups, except for hip flexors which remained stable. Generally, men were stronger and showed a significant greater rate of decline of muscle strength than women. The adult and late-onset phenotypes taken separately also showed a significant and similar decline over the 9-year period, except for the wrist and knee extensors where muscle strength of participants with the adult phenotype decreased faster than in the late-onset phenotype. The similar rate of decline of muscle strength loss observed between phenotypes highlights the need to develop interventions to prevent this decline, even for patients with the late-onset phenotype who are often considered as mildly impaired, and therefore neglected by the rehabilitation services. PMID- 29785526 TI - Education and Physical Health Trajectories in Later Life: A Comparative Study. AB - The cumulative (dis)advantage hypothesis states that health disparities between education groups increase with age. The present study examined this hypothesis in a comparative analysis of the United States, the United Kingdom, the Netherlands, and Sweden. These countries offer sharp contrasts in the social conditions that may intensify or inhibit processes of cumulative (dis)advantage. Using harmonized panel data from the HRS, ELSA, and SHARE, the study applied Poisson multilevel regression models to trace changes in the number of chronic conditions and functional limitations of people aged 50-76 (N = 16,887 individuals; 71,154 observations). The four countries showed a clear gradient in levels of physical health and in the extent to which health trajectories were shaped by education. Across all ages and cohorts, health problems were most prevalent in the United States, less prevalent in the United Kingdom and the Netherlands, and least prevalent in Sweden. A similar cross-national gradient was found for the size of health gaps between education groups and for the extent to which these gaps widened with age. Gaps were largest in the United States, smaller in the United Kingdom and in the Netherlands, and smallest in Sweden. PMID- 29785527 TI - Birth Intervals and Health in Adulthood: A Comparison of Siblings Using Swedish Register Data. AB - A growing body of research has examined whether birth intervals influence perinatal outcomes and child health as well as long-term educational and socioeconomic outcomes. To date, however, very little research has examined whether birth spacing influences long-term health. We use contemporary Swedish population register data to examine the relationship between birth-to-birth intervals and a variety of health outcomes in adulthood: for men, height, physical fitness, and the probability of falling into different body mass index categories; and for men and women, mortality. In models that do not adjust carefully for family background, we find that short and long birth intervals are clearly associated with height, physical fitness, being overweight or obese, and mortality. However, after carefully adjusting for family background using a within-family sibling comparison design, we find that birth spacing is generally not associated with long-term health, although we find that men born after very long birth intervals have a higher probability of being overweight or obese in early adulthood. Overall, we conclude that birth intervals have little independent effect on long-term health outcomes. PMID- 29785528 TI - A rare case of ascending colon adenocarcinoma incarcerated in an inguinoscrotal hernia: case report and literature review. AB - BACKGROUND: Inguinal hernias and colorectal cancers are common conditions, but the presentation of a loop of bowel containing cancer within a hernia is rare. Principles of surgery include oncological resection of the involved colonic segment as well as lymphatic drainage. Based on case reports of the last several decades, there have been no reports of a case where the reduction of an inguinoscrotal hernia and oncological colectomy were performed completely laparoscopically. We present the first instance of a completely laparoscopically assisted resection and hernia repair on a patient with T4 ascending colon cancer. A literature search on recent case reports over the last 30 years has also been presented with a focus on trends in treatment. CASE PRESENTATION: An 83-year-old man presented for further investigation of his iron deficiency anaemia and was diagnosed with adenocarcinoma of the ascending colon. This was demonstrated radiologically to be found within a large right inguinoscrotal hernia. He underwent a laparoscopically assisted right hemicolectomy and laparoscopic closure of the internal ring and recovered well. CONCLUSIONS: Colorectal cancers within inguinal hernias are rare and can often present with complications such as perforation. As such, treatment has mostly involved an open operation. The last few years have shown feasibility of a laparoscopic approach and can be attempted safely when indicated. PMID- 29785529 TI - Isolation and characterization of Bacillus sp. GFP-2, a novel Bacillus strain with antimicrobial activities, from Whitespotted bamboo shark intestine. AB - The abuse of antibiotics and following rapidly increasing of antibiotic-resistant pathogens is the serious threat to our society. Natural products from microorganism are regarded as the important substitution antimicrobial agents of antibiotics. We isolated a new strain, Bacillus sp. GFP-2, from the Chiloscyllium plagiosum (Whitespotted bamboo shark) intestine, which showed great inhibitory effects on the growth of both Gram-positive and Gram-negative bacteria. Additionally, the growth of salmon was effectively promoted when fed with inactivated strain GFP-2 as the inhibition agent of pathogenic bacteria. The genes encoding antimicrobial peptides like LCI, YFGAP and hGAPDH and gene clusters for secondary metabolites and bacteriocins, such as difficidin, bacillibactin, bacilysin, surfactin, butirosin, macrolactin, bacillaene, fengycin, lanthipeptides and LCI, were predicted in the genome of Bacillus sp. GFP-2, which might be expressed and contribute to the antimicrobial activities of this strain. The gene encoding beta-1,3-1,4-glucanase was successfully cloned from the genome and this protein was detected in the culture supernatant of Bacillus sp. GFP-2 by the antibody produced in rabbit immunized with the recombinant beta-1,3-1,4-glucanase, indicating that this strain could express beta-1,3-1,4-glucanase, which might partially contribute to its antimicrobial activities. This study can enhance a better understanding of the mechanism of antimicrobial activities in genus Bacillus and provide a useful material for the biotechnology study in antimicrobial agent development. PMID- 29785531 TI - Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure. AB - OBJECTIVE: To evaluate the association of two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with recurrent miscarriage (RM) and repeated implantation failure (RIF) METHODS: The study comprised of 521 patients, with a history of RM (n = 370) or RIF (n = 151). One hundred forty-four women with fallopian tube blockages who had successfully conceived after the first in vitro fertilization embryo transfer treatment served as the control group. The MTHFR alleles, genotypes, and haplotypes were assessed in different groups. RESULTS: There was no difference in allele frequency and distribution of MTHFR polymorphisms between case and control patients. The 1298AA genotype was represented in a higher frequency, and 1298AC genotype was significantly lower in subfertile group when compared to the control group. A significant relationship was found between the 1298AC genotype and the RIF subgroup. The haplotype 677CC/1298AA was overrepresented in the RM subgroup (> 2 times) and haplotype 677CC/1298AC was underrepresented in the RIF subgroup (P < 0.05). Nevertheless, these two haplotypes were not connected to fertilization and embryo cleavage rates. CONCLUSION: Our findings indicate that the MTHFR gene polymorphism might play a role in the etiology of patients with RM or RIF. No adverse effects of different MTHFR haplotypes on embryo development were detected. Further studies on the biological role are needed to better understand the susceptibility to pregnancy complications. PMID- 29785530 TI - Azoospermia and embryo morphokinetics: testicular sperm-derived embryos exhibit delays in early cell cycle events and increased arrest prior to compaction. AB - PURPOSE: Sperm play an essential role in embryonic genome activation and embryonic progression to blastocyst. In the present work, we focus on development of embryos created as a result of ICSI with testicular or epididymal sperm from azoospermic males and compare this to outcomes from normospermic males. The objective of this study was to determine if sperm origin influences clinical outcomes, the kinetics of embryo development, or the incidence of cleavage anomalies and multinucleation. METHODS: A total of 93 consecutive intracytoplasmic sperm injection cycles (ICSI) performed for 83 couples were included in this study. Observations were made on 594 fertilized oocytes cultured in the EmbryoScope using time-lapse microscopy (TLM). Epididymal sperm (n = 29) cycles or surgically retrieved sperm from the testis (TESE; n = 37 cycles) of men with either obstructive (OA) or non-obstructive azoospermia (NOA) were used to inject oocytes. A further 27 ICSI cycles were performed using ejaculated sperm from normospermic males, designated as our control sperm (CS) group. Kinetic data and cycle outcomes were retrospectively analyzed. RESULTS: The clinical pregnancy rate was not different between the three groups (TESE 51.4%, PESA 57.7%, and CS 59.3%). A non-significant decrease was observed in both implantation (30.9%) and live birth rate (43%) with TESE as compared to PESA (35.3%, 58%, respectively) and CS groups (45.1%, 56%, respectively). Failure to compact was significantly higher amongst TESE-NOA embryos (35.2%; P < 0.001) as compared to TESE-OA (4%), PESA (9%), and CS (3.8%) embryos. The two points at which TESE-derived embryos (both NOA and OA) behaved most differently from PESA and CS embryos was at cc2 (t3-t2; time to initiation of the second cell cycle) and tSB (time to start of blastulation). A significantly lower percentage of TESE embryos exhibited kinetics typically ascribed to high quality embryos with the greatest developmental potential. Finally, the incidence of direct uneven cleavage (DUC) was observed to be significantly higher after ICSI with sperm retrieved from azoospermic males. CONCLUSIONS: TLM allowed a more in depth comparison of paternal influence on embryo morphokinetics and helped to identify specific differences in cell cycle kinetics. TESE-NOA embryos exhibited a higher incidence of compaction failure. PMID- 29785532 TI - Comparison of intracytoplasmic sperm injection outcome with fresh versus frozen thawed testicular sperm in men with nonobstructive azoospermia: a systematic review and meta-analysis. AB - PURPOSE: The purpose of the study is to explore testicular sperm cryopreservation in patients with nonobstructive azoospermia (NOA) whether affect the outcome of subsequent intracytoplasmic sperm injection (ICSI). METHODS: A systematic review and meta-analysis was conducted by searching the MEDLINE and EMBASE databases for relevant published studies in English language (1997-2017). Studies were eligible if they included the comparison of using fresh and frozen-thawed testicular sperm followed by ICSI. Two reviewers independently performed data extraction, quality assessment and assessed the risk of bias. The overall summary risk estimated the number of events. A meta-analysis was conducted using a random effects or fixed effects model analysis according to the test of heterogeneity. RESULTS: A total of 17 studies with 1,261 ICSI cycles were identified. Analysis of the present data showed no difference in the fertilization outcome when comparing fresh versus frozen-thawed spermatozoa (RR = 1.02, 95% CI 0.86-1.09). Similarly, no difference in CR (RR = 1.01, 95% CI 0.96-1.05), good embryo rate (RR = 1.01, 95% CI 0.95-1.09), and IR (RR = 0.93, 95% CI 0.66-1.30) was observed if the spermatozoa was fresh or frozen-thawed. Finally, no difference in CPR or LBR was noted when using fresh or frozen-thawed cycles were analyzed separately (RR = 1.03, 95% CI 0.86-1.24; RR 1.11, 95% CI 0.88-1.41, respectively). CONCLUSIONS: In men with NOA, the ICSI outcome is not affected by whether the retrieved testicular sperm is fresh or frozen. Sperm cryopreservation ought to be considered in every surgical sperm retrieval case, which remain feasible even in patients with few testicular sperm retrieved. PMID- 29785533 TI - Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence. AB - Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association. PMID- 29785535 TI - Effects of trypsinization and of a combined trypsin, collagenase, and DNase digestion on liberation and in vitro function of satellite cells isolated from juvenile porcine muscles. AB - Muscle stem cells, termed satellite cells (SC), and SC-derived myogenic progenitor cells (MPC) are involved in postnatal muscle growth, regeneration, and muscle adaptability. They can be released from their natural environment by mechanical disruption and tissue digestion. The literature contains several isolation protocols for porcine SC/MPC including various digestion procedures, but comparative studies are missing. In this report, classic trypsinization and a more complex trypsin, collagenase, and DNase (TCD) digestion were performed with skeletal muscle tissue from 4- to 5-d-old piglets. The two digestion procedures were compared regarding cell yield, viability, myogenic purity, and in vitro cell function. The TCD digestion tended to result in higher cell yields than digestion with solely trypsin (statistical trend p = 0.096), whereas cell size and viability did not differ. Isolated myogenic cells from both digestion procedures showed comparable proliferation rates, expressed the myogenic marker Desmin, and initiated myogenic differentiation in vitro at similar levels. Thus, TCD digestion tended to liberate slightly more cells without changes in the tested in vitro properties of the isolated cells. Both procedures are adequate for the isolation of SC/MPC from juvenile porcine muscles but the developmental state of the animal should always be considered. PMID- 29785534 TI - An enzyme-free homogenous electrochemical assay for sensitive detection of the plasmid-mediated colistin resistance gene mcr-1. AB - Antibiotic resistance associated with the mcr-1 gene of Gram-negative bacteria, which confers resistance to drugs of last resort and has the potential to spread via plasmids, is one of the most pressing issues facing global health today. Point-of-care testing for the mcr-1 gene is needed to aid in the identification of colistin resistance in the field and to control its horizontal transmission. Here, we report the successful development of an enzyme-free homogenous electrochemical strategy for sensitive detection of the antibiotic resistance gene mcr-1 using the hybridization chain reaction and mcr-1-specific toehold probe. The long double-stranded DNA polymer produced using this strategy could be detected by assessing the diffusion of methylene blue towards the surface of a screen-printed gold electrode. Under optimized conditions, a linear relationship was observed between the variation of peak current and the natural logarithm of the mcr-1 gene concentration in the range of 1 nM to 1 MUM with a detection limit of 0.78 nM (S/N = 3). This enzyme-free, isothermal platform is a rapid, portable, disposable, and sensitive method for detection of plasmid-mediated colistin resistance. PMID- 29785539 TI - The Effect of Spironolactone on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Catheterization: Study Design and Rationale. AB - INTRODUCTION: Patients undergoing coronary catheterization are at high risk of developing contrast-induced nephropathy (CIN) acute kidney injury (AKI). Several approaches have been supposed to limit such an effect but with mixed results or non-practical methods. Spironolactone is supposed to be effective as a nephroprotective agent in animal studies. This study will try to measure the effect of spironolactone on the incidence of CIN-AKI in patients undergoing coronary catheterization (angiography angioplasty). METHODS: This study is a single-center, investigator-driven, double-blinded randomized controlled study in Iraq-Basra. More than 400 patients admitted for coronary angio unit in our center will be allocated in a 1:1 ratio to receive either spironolactone 200 mg single dose or placebo in addition to their usual premedication. PLANNED OUTCOMES: Primary end point will be CIN defined as more than 25% or 0.3 mg/dl elevation in serum creatinine (S.Cr.) from baseline during the first 2-3 days after the procedure. We hope to identify or answer an important question regarding CIN in such high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03329443. PMID- 29785537 TI - Differentiation of benign and malignant ampullary obstruction by multi-row detector CT. AB - PURPOSE: To determine useful CT parameters to differentiate ampullary carcinomas from benign ampullary obstruction. MATERIALS AND METHODS: This study included 93 patients who underwent abdominal CT, 31 patients with ampullary carcinomas, and 62 patients with benign ampullary obstruction. Two radiologists independently evaluated CT parameters then reached consensus decisions. Statistically significant CT parameters were identified through univariate and multivariate analyses. RESULTS: In univariate analysis, the presence of ampullary mass, asymmetric, abrupt narrowing of distal common bile duct (CBD), dilated intrahepatic bile duct (IHD), dilated pancreatic duct (PD), peripancreatic lymphadenopathy, duodenal wall thickening, and delayed enhancement were more frequently in ampullary carcinomas observed (P < 0.05). Multivariate logistic regression analysis using significant CT parameters and clinical data from univariate analysis, and clinical symptom with jaundice (P = 0.005) was an independent predictor of ampullary carcinomas. For multivariate analysis using only significant CT parameters, abrupt narrowing of distal CBD was an independent predictor of ampullary carcinomas (P = 0.019). Among various CT criteria, abrupt narrowing of distal CBD and dilated IHD had highest sensitivity (77.4%) and highest accuracy (90.3%). CONCLUSION: The abrupt narrowing of distal CBD and dilated IHD is useful for differentiation of ampullary carcinomas from benign entity in patients without the presence of mass. PMID- 29785536 TI - Wnt3a promotes differentiation of human bone marrow-derived mesenchymal stem cells into cementoblast-like cells. AB - Cementum is a calcified, avascular connective tissue that laminates the root of a tooth and plays a pivotal role in the development, homeostasis, and regeneration of a periodontal tissue. As a potential treatment for periodontal tissue defects in the patient with chronic periodontitis, much attention has been paid to tissue engineering combined with mesenchymal stem cells for regenerating periodontal tissues including cementum. However, limited information is available for the molecular factors that have impacts on the differentiation of mesenchymal stem cells into cementoblasts. Here, we focus on the effect of Wnt3a as a potential inducer and tested the effect of this protein in vitro using human bone marrow derived mesenchymal stem cells. It was found that, when cells were cultured in an osteogenic medium containing Wnt3a, cementoblast-specific genes, such as cementum protein 1 and cementum attachment protein, as well as bone-related genes were significantly upregulated. These results suggest that Wnt3a promotes differentiation of the cells into cementoblast-like cells. Further experiments were carried out using inhibitors to gain deeper insights into molecular mechanisms underlying the observed differentiation. As a result, we conclude that Wnt3a-triggered differentiation into cementoblast-like cells is the consequence of the activation of the canonical Wnt signaling pathway with possible involvement of the non-canonical pathway. PMID- 29785538 TI - Stress phase angle regulates differentiation of human adipose-derived stem cells toward endothelial phenotype. AB - Endothelial cells are subjected to cyclic shear by pulsatile blood flow and pressures due to circumferential stresses. Although most of the researches on this topic have considered the effects of these two biomechanical forces separately or concurrently, few studies have noticed the interaction of these cyclic loadings on endothelial behavior. Negative temporal stress phase angle, defined by the phase lag between cyclic shear and tensile stresses, is an established parameter which is known to have substantial effects on blood vessel remodeling and progression of some serious cardiovascular diseases. In this research, intermittent shear and tensile stresses with different stress phase angle values were applied on human adipose stem cells (ASC). The expression level of three major endothelial-specific genes, elastic modulus of cells and cytoskeleton actin structure of cells were studied and compared among control and three test groups subjected to stress phase angle values at 0 degrees , - 45 degrees , and - 90 degrees . Mechanical properties of ASCs were determined by atomic force microscopy and actin fiber structure was visualized by confocal imaging through Phalloidin staining. Results described a decrease in expression of FLK-1 and VE-cadherin and rise of vWF marker expression in case of higher negative stress phase angles. The Young's moduli of cells were significantly higher and cytoskeletal actin structure was more organized with higher thickness for all test samples subjected to combined stresses; however, these features were less magnificent for applied stress phase angles with higher negative values. The results confirmed significant effects of SPA on endothelial differentiation of mesenchymal stem cells. PMID- 29785540 TI - Use of magnetic resonance imaging in rectal cancer patients: Society of Abdominal Radiology (SAR) rectal cancer disease-focused panel (DFP) recommendations 2017. AB - PURPOSE: To propose guidelines based on an expert-panel-derived unified approach to the technical performance, interpretation, and reporting of MRI for baseline and post-treatment staging of rectal carcinoma. METHODS: A consensus-based questionnaire adopted with permission and modified from the European Society of Gastrointestinal and Abdominal Radiologists was sent to a 17-member expert panel from the Rectal Cancer Disease-Focused Panel of the Society of Abdominal Radiology containing 268 question parts. Consensus on an answer was defined as >= 70% agreement. Answers not reaching consensus (< 70%) were noted. RESULTS: Consensus was reached for 87% of items from which recommendations regarding patient preparation, technical performance, pulse sequence acquisition, and criteria for MRI assessment at initial staging and restaging exams and for MRI reporting were constructed. CONCLUSION: These expert consensus recommendations can be used as guidelines for primary and post-treatment staging of rectal cancer using MRI. PMID- 29785542 TI - Perioperative hemorrhagic complications in pelvic floor reconstructive surgery. AB - INTRODUCTION AND HYPOTHESIS: We sought to assess the incidence, symptoms, and risk factors of perioperative hemorrhagic complications in patients undergoing pelvic floor reconstructive surgery. METHODS: This is a retrospective study on 694 consecutive patients who underwent pelvic floor reconstructive surgery with or without using mesh in our hospital over a 3-year period. RESULTS: We identified 694 pelvic floor reconstructive procedures from 2014 to 2016, including complete/incomplete colpocleisis (176, 25.4%), sacral colpopexy/hysteropexy with mesh (140, 20.1%), colporrhaphy (77, 11.1%) or vaginal mesh repair (99, 43.1%). Two patients who received only sacrospinous ligament suspension were excluded. There were 68 (9.8%) and 3 (0.1%) patients whose blood loss reached 200 and 500 ml respectively. Procedures involving mesh and vaginal hysterectomy (VH) caused more intraoperative blood loss. Postoperative hemoglobin drop was least in colpocleisis (p < 0.05). All 6 of the patients (0.9%) who developed postoperative pelvic hematoma underwent concomitant VH, and 5 of them received mesh. CONCLUSIONS: Hemorrhagic complications during or after pelvic floor reconstructive surgery are rare. Mesh use and concomitant VH are two major surgical risk factors for hemorrhagic complications in pelvic floor reconstructive surgery. PMID- 29785541 TI - New observations in tumor cell plasticity: mutational profiling in a case of metastatic melanoma with biphasic sarcomatoid transdifferentiation. AB - We describe a highly unusual case of metastatic melanoma in a 61-year-old female that manifested as a single groin lymph node metastasis accompanied by two distinct, subcutaneous sarcomatoid tumors on the same leg, without evidence of a primary tumor. Characterization encompassed extensive immunohistochemical staining as well as next-generation sequencing (NGS). The lymph node metastasis showed obvious features of melanoma. The two subcutaneous lesions, however, were morphologically and immunohistochemically consistent with high-grade myxofibrosarcoma and soft tissue mixed tumor, respectively. All three lesions were BRAF wild-type and found to harbor an identical NRAS p.Q61R mutation. Metachronic intestinal metastases, showing intermingled conventional and sarcomatoid morphology, as well as an identical genetic phenotype, corroborated these findings. The concordant genetic profile provided evidence of biphasic sarcomatoid transdifferentiation of melanoma. Interestingly, the lack of genetic heterogeneity between the three morphologically distinct tumors suggests factors other than genetic mutations to be involved in melanoma transdifferentiation. PMID- 29785545 TI - Development of GP and GEP models to estimate an environmental issue induced by blasting operation. AB - Air overpressure (AOp) is one of the most adverse effects induced by blasting in the surface mines and civil projects. So, proper evaluation and estimation of the AOp is important for minimizing the environmental problems resulting from blasting. The main aim of this study is to estimate AOp produced by blasting operation in Miduk copper mine, Iran, developing two artificial intelligence models, i.e., genetic programming (GP) and gene expression programming (GEP). Then, the accuracy of the GP and GEP models has been compared to multiple linear regression (MLR) and three empirical models. For this purpose, 92 blasting events were investigated, and subsequently, the AOp values were carefully measured. Moreover, in each operation, the values of maximum charge per delay and distance from blast points, as two effective parameters on the AOp, were measured. After predicting by the predictive models, their performance prediction was checked in terms of variance account for (VAF), coefficient of determination (CoD), and root mean square error (RMSE). Finally, it was found that the GEP with VAF of 94.12%, CoD of 0.941, and RMSE of 0.06 is a more precise model than other predictive models for the AOp prediction in the Miduk copper mine, and it can be introduced as a new powerful tool for estimating the AOp resulting from blasting. PMID- 29785543 TI - Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide. AB - BACKGROUND: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. METHODS: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. RESULTS: Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71-88) vs. Japan: 78 (70-84) years; p = 0.947], glomerular filtration rate [UK: 49 (34-68) vs. Japan: 49 (33-65) ml/min/1.73 m2; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278-10,977) vs. Japan: 4155 (1972-9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105-131) vs. 137 (118-159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. CONCLUSIONS: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan. PMID- 29785544 TI - HeartMate II implantation technique that spares the sternum and ascending aorta. AB - Left ventricular assist devices (LVADs) have become the standard therapy for patients with end-stage heart failure, and the use of LVADs for long-term support has grown exponentially over the past decade. As the number of LVAD implantations has increased, surgeons have faced more challenging cases, such as those in which the patient has previously undergone a sternotomy. The HeartMate II is one of the most widely implanted LVADs. The standard procedure for HeartMate II implantation is median sternotomy and sewing the outflow graft to the ascending aorta. However, in patients with sternal comorbidities, it can be advantageous to use a less invasive approach that avoids this procedure. We describe the case of a 64 year-old man with a history of end-stage ischemic cardiomyopathy who had previously undergone a median sternotomy and a coronary artery bypass grafting operation and had patent grafts. He required a HeartMate II LVAD (destination therapy), which was implanted via a left subcostal incision; the pump was placed subdiaphragmatically, and the outflow graft was sewed to the descending aorta to avoid a complicated redo cardiac operation via median sternotomy and to minimize the risk of injuring the patent bypass grafts. The patient survived for more than 500 days postoperatively. This approach is feasible and could be a safer method for implanting a HeartMate II device in patients with serious comorbidities that preclude the use of the traditional implantation techniques. PMID- 29785546 TI - Diagnosis and management of primary hepatic pregnancy: literature review of 31 cases. AB - PURPOSE: To summarize the appropriate diagnostic methods and therapeutic options for primary hepatic pregnancy (PHP). METHODS: Literature searches were performed in Pubmed, Web of Science, Cochrane Library and Embase databases (1956-2017), using the following search terms: primary hepatic pregnancy, hepatic pregnancy, liver pregnancy, hepatic ectopic pregnancy and intrahepatic pregnancy. Further literature was confirmed through cross-referencing. RESULTS: Thirty-one cases were reviewed and collected. The site mostly described in literatures is the right lobe of liver (93.5%). Main symptoms of PHP included abdominal pain (77.4%), amenorrhea (45.2%), acuteperitonism (32.3%), shock (25.8%) and vomit (16.1%). Majority of patients (83.9%) were treated by laparotomy. Less-invasive approaches (16.1%) such as laparoscopy or combination of postoperative injection of methotrexate were used less frequently. The outcome was acceptable at the end of the follow-up period in ten cases (1-72 months) and the recovery rate was 96.7%. One patient died and other complications were noted in three patients during the postoperative period. CONCLUSIONS: The clinical diagnosis of PHP can be settled up by comprehensive analysis of serum HCG levels, ultrasound and imaging. The analysis should be assessed carefully before therapeutic procedure. Invasive methods should be preferential. Less-invasive approaches can be selected when the patients have stable hemodynamics and non-acute abdomen. PMID- 29785547 TI - Analysis of factors affecting outcomes of pregnancy complicated by Echinococcus: an algorithm for approach and management. AB - PURPOSE: The management of hydatid disease (HD) co-occurring with pregnancy remains a challenge for physicians. We aimed to determine factors that were related to fetal and maternal outcomes in HD complicated pregnancies and then develop an approach/treatment algorithm. METHOD: All patients at the participating hospitals were first analyzed to determine whether they had HD. Only patients diagnosed with HD during the course of their pregnancy were included. Certain cyst-related factors (diameter, localization, increase in size, and viability) and certain pregnancy-related factors (treatments, gestational week, maternal co-morbidities, and delivery type) were investigated. Nonlinear principal component analysis (NPCA) was performed to determine the relationships between the categories of variables. RESULTS: Out of 12,926 pregnancies, 27 cases were diagnosed with HD. In 13 cases, each developed at least one fetal problem. Using Albendazol in first trimester, presence of an active cyst, increased diameter by more than 1 cm during pregnancy and a cyst diagnosed in the second trimester were associated with at least one fetal problem. According to the NPCA results, cyst diameter when first diagnosed was related to fetal outcomes; a cyst greater than 10 cm was associated with "at least one fetal problem". Cysts 5-10 cm in diameter were in a neutral position, while 2-5 cm in diameter were in the "no problems" group. CONCLUSIONS: HD mostly affects fetus. If cyst-related and pregnancy-related variables are optimal, close follow-up on a monthly is the best course of action. However, in high-risk conditions, percutaneous interventions or surgery should be considered. PMID- 29785548 TI - Operative vaginal delivery in case of persistent occiput posterior position after manual rotation failure: a 6-month follow-up on pelvic floor function. AB - PURPOSE: To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. METHODS: A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. RESULTS: Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p < 0.001) without increasing neonatal morbidity. At 6 months postpartum, AD in OP position was associated with higher rate of anal incontinence (30% vs. 5.5%, p = 0.001) and with more urinary symptoms, dyspareunia and perineal pain. CONCLUSIONS: OP operative deliveries are associated with significant perineal morbidity and pelvic floor dysfunction at 6 months postpartum. PMID- 29785549 TI - Once episiotomy, always episiotomy? AB - OBJECTIVE: To investigate the association between episiotomy and perineal damage in the subsequent delivery. STUDY DESIGN: A retrospective cohort study was conducted, comparing outcome of subsequent singleton deliveries of women with and without episiotomy in their first (index) delivery. Deliveries occurred between the years 1991-2015 in a tertiary medical center. Traumatic vaginal tears, multiple pregnancies, and cesarean deliveries (CD) in the index pregnancy were excluded from the analysis. Multiple logistic regression models were used to control for confounders. RESULTS: During the study period, 43,066 women met the inclusion criteria; of them, 50.4% (n = 21,711) had subsequent delivery after episiotomy and 49.6% (n = 21,355) had subsequent delivery without episiotomy in the index pregnancy. Patients with episiotomy in the index birth higher rates of subsequent episiotomy (17.5 vs. 3.1%; P < 0.001; OR 1.9; 95% CI). In addition, the rates of the first and second degree perineal tears as well as the third and fourth degree perineal tears were significantly higher in patients following episiotomy (33.6 vs. 17.8%; P < 0.001, and 0.2 vs. 0.1%; P = 0.002, respectively). Nevertheless, there was no significant difference at the rates of CD and instrumental deliveries, between the groups. While adjusting for maternal age, ethnicity, birth weight, and vacuum delivery-the previous episiotomy was noted as an independent risk factor for recurrent episiotomy in the subsequent delivery (adjusted OR 6.7; 95% CI 6.2-7.3, P < 0.001). The results remained significant for term (adjusted OR 6.8; 95% CI 6.2-7.4, P < 0.001) as well as preterm deliveries (adjusted OR 4.5; 95% CI 3.3-6.3, P < 0.001) in two different models. CONCLUSION: Episiotomy is an independent risk factor for recurrent episiotomy in the subsequent delivery. PMID- 29785550 TI - Does tumor grade influence the rate of lymph node metastasis in apparent early stage ovarian cancer? AB - PURPOSE: To evaluate the prevalence of regional lymph node (LN) metastasis in patients with non-clear cell epithelial ovarian cancer apparently confined to the ovary, stratified by tumor grade. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was accessed (1988 2014). We identified patients with epithelial ovarian carcinoma of serous, endometrioid and mucinous histology apparently confined to the ovary who underwent extensive lymphadenectomy (defined as at least 20 lymph nodes removed). Demographics, tumor histology, grade and lymph node status were collected. Comparisons were made with Chi square and Mann-Whitney U tests. RESULTS: A total of 1242 women met the inclusion criteria. Endometrioid adenocarcinoma was the most common histology (564 patients (45.4%)) while 443 (35.7%) and 235 (18.9%) patients had serous, and mucinous adenocarcinoma, respectively. The rate of LN metastasis in low-grade serous was 9.0% (6/67) vs. 14.4% (54/376) in high-grade serous histology (OR, 1.71, 95% CI 0.70, 4.14, p = 0.24). In patients with low grade endometrioid tumors, the rate of LN metastasis was 1.7% (7/407) vs. 5.1% (8/157) observed in those with high-grade tumors (OR: 3.07, 95% CI 1.09, 8.61, p = 0.033). Lastly, the rate of LN metastasis in mucinous histology was 1.7% (3/177) in low-grade vs. 8.6% (5/58) in high-grade tumors (OR: 5.47, 95% CI 1.27, 23.66, p = 0.024). CONCLUSIONS: Regional LN metastasis in apparent stage I low grade mucinous and endometrioid ovarian tumors is infrequent. PMID- 29785552 TI - Suppression of pupillary unrest by general anesthesia and propofol sedation. AB - The pupil undergoes irregular oscillations when exposed to light. These oscillations, known as pupillary unrest in ambient light, originate from oscillatory activity within the Edinger-Westphal nucleus in the midbrain. The midbrain and upper pons also contain nuclei known to be very sensitive to the effects of anesthetics that play a central role in maintaining wakefulness. We hypothesized that anesthetics may display similar effects on wakefulness and pupillary unrest. Repeat measurements of pupillary unrest using infrared pupillometry were performed in 16 patients undergoing general anesthesia and 8 patients undergoing propofol sedation. Pupil scans were analyzed using fast Fourier transformation to quantify the effects of the anesthetics on pupillary unrest. During general anesthesia and deep sedation, observed pupillary unrest values below 0.1 (AU) indicate complete suppression of pupillary oscillations. Pupillary unrest decreased more during general anesthesia [to 24% of baseline (95% CI 17-30%)] than pupil size [51% of baseline (95% CI 45-57%)]. Sedation with propofol was associated with a reduction in pupillary unrest that was correlated to the depth of sedation as assessed by the Richmond Agitation-Sedation Scale and the processed electroencephalogram. Pupillary unrest is caused by oscillatory activity within the midbrain that is affected by the state of wakefulness or by hypnotics directly. Increased sedation and general anesthesia reduce and then abolish pupillary unrest as wakefulness decreases. We speculate that midbrain nuclei responsible for wakefulness and pupillary unrest are either communicating or share a similar sensitivity to the effects of commonly used anesthetics. PMID- 29785551 TI - Salivary duct carcinoma: evaluation of treatment and outcome in a tertiary referral institute. AB - PURPOSE: The aggressive behavior of salivary duct carcinoma (SDC) necessitates an aggressive treatment strategy, including surgery and radiotherapy (RT). We evaluated practice patterns and treatment outcomes in patients with SDC treated in our Institute. METHODS: Patients with SDC of the parotid or submandibular gland treated with curative intention in our Institute from 1998 until 2016 were reviewed. Our diagnostic workup and treatment strategy were evaluated together with treatment outcomes. RESULTS: Fifteen patients with SDC were included. Staging included MRI and ultrasound-guided fine needle aspiration cytology. Only in a minority (20%) of patients, the preoperative diagnosis of SDC was raised due to positive immunohistochemical staining for the androgen receptor (AR) on cytology. All patients were treated with (sub)total resection of the salivary gland and 53% underwent a therapeutic neck dissection. All patients except one received postoperative RT. Immunohistochemical staining was found positive for AR (100%) and human epidermal growth factor receptor 2 (HER2/neu) (13%). No local recurrences occurred. Regional and distant failure rates were 20% and 40%, respectively. CONCLUSIONS: Excellent local control rates can be achieved with extensive (local) surgical treatment and postoperative RT. In case of lymph node metastases, a neck dissection with adjuvant postoperative RT is warranted. In patients with node-negative disease, a less aggressive approach for the neck seems feasible to reduce treatment-related morbidity. PMID- 29785553 TI - Antituberculosis Drug-Induced Fixed Drug Eruption: A Case Report. AB - Fixed drug eruption (FDE) was caused by fixed-dose combination (FDC) of antituberculosis drugs in the form of tablet Forecox(r) (rifampicin [rifampin] 225 mg + isoniazid 150 mg + pyrazinamide 750 mg + ethambutol 400 mg) in a 40-year old male patient with a history of drug allergy. The patient developed FDE after taking the third dose of tablet Forecox(r) for pulmonary tuberculosis. Tablet Forecox(r) was withdrawn and the patient recovered from the reaction after 15 days of treatment for FDE. As per World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and Naranjo causality assessment criteria, the association between the reaction and tablet Forecox(r) was possible and probable, respectively. The reaction was moderately (Level 4b) severe according to the Modified Hartwig and Siegel scale. As there is an increased risk of allergic reaction in patients with a history of drug allergy, FDCs should not be used in order to avoid complexity in identifying the culprit drug. PMID- 29785556 TI - Bilateral simultaneous "Santosh Post-graduate Institute tubularized flap pyelovesicostomy" in a case of bilateral pelvi-ureteric junction obstruction with bilateral giant hydronephrosis. AB - We present a case of bilateral giant hydronephrosis (HDN) secondary to bilateral pelvi-ureteric junction obstruction (PUJO) in a young girl, managed successfully by robot-assisted bilateral tubularized flap pyelo-vesicostomy. This case report highlights the feasibility, reproducibility and technicalities of this procedure. PMID- 29785555 TI - Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis. AB - RATIONALE: This study aims to examine whether folate/folic acid/methylfolate/folinic acid supplemented to antipsychotics (FA + AP) is beneficial in schizophrenia treatment. OBJECTIVE: We conducted a comprehensive systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials (RCTs) of FA + AP for schizophrenia. METHODS: The primary outcome was an improvement in total symptoms. Other outcomes were psychopathology subscales (positive, negative, general, and depressive symptoms), discontinuation due to all-cause and adverse events, and individual adverse events. The meta-analysis evaluated the effect size based on a random-effects model. RESULTS: Although we included ten RCTs with 925 patients in total (seven folic acid RCTs (n = 789), two methylfolate RCTs (n = 96), and one folinic acid RCT (n = 40)) in the systematic review, only seven RCTs were included in the meta analysis. Pooled FA + AP treatments were not superior to placebo + AP in the improvement of total (N = 7, n = 340; standardized mean difference (SMD) = - 0.20, 95% confidence interval (CI) = - 0.41, 0.02, p = 0.08, I2 = 0%), positive, general, or depressive symptoms. Pooled FA + AP treatments were more effective than placebo + AP for negative symptoms (N = 5, n = 281; SMD = -0.25, 95% CI = 0.49, -0.01, p = 0.04, I2 = 0%). Although pooled FA + AP treatments were associated with a lower incidence of serious adverse events than placebo treatments (N = 4, n = 241; risk ratio = 0.32, 95% CI = 0.12-0.82, p = 0.02, I2 = 0%; number needed to harm = not significant), there were no significant differences in other safety outcomes between both treatments. CONCLUSIONS: Our findings suggest that pooled FA + AP treatment improves negative symptoms in schizophrenia patients. Moreover, this treatment was well tolerated. However, because our results might exhibit a small-study effect, future studies with a larger sample should be conducted to obtain more robust results. PMID- 29785554 TI - Interactions between kappa and mu opioid receptor agonists: effects of the ratio of drugs in mixtures. AB - RATIONALE: Pain is the leading reason for seeking health care, and mu opioid receptor agonists continue to be prescribed despite well-documented adverse effects. Kappa opioid receptor agonists have antinociceptive effects with little to no abuse liability and might be useful for treating pain in mixtures. Kappa:mu opioid mixtures might be useful if therapeutic effects of each drug can be selectively increased while reducing or avoiding the adverse effects that occur with larger doses of each drug alone. OBJECTIVE: This study characterized the effects of the kappa opioid receptor agonist spiradoline alone (0.32-56 mg/kg) and in 1:10, 1:3, 1:1, and 3:1 mixtures with the mu opioid receptor agonists morphine (1.0-32 mg/kg) and etorphine (1-10 MUg/kg) on warm water tail-withdrawal latency, body temperature, responding for food, and fecal output in male Sprague Dawley rats (n = 24). RESULTS: Antinociceptive effects were greater than additive for 1:10 and 1:3 spiradoline:morphine mixtures and for 1:10, 1:3, and 1:1 spiradoline:etorphine mixtures. The potency of spiradoline to produce hypothermia was greater with 1:3 and 3:1 spiradoline:etorphine mixtures but not with 1:10 or 1:1 mixtures or with any spiradoline:morphine mixture. The effects of 1:3 spiradoline:morphine on responding for food were additive, whereas 1:1 and 3:1 were greater than additive. Spiradoline did not significantly alter morphine induced decreases in fecal output. CONCLUSIONS: Overall, mixtures of kappa and mu opioids might have therapeutic potential for treating pain, particularly when the mixture has a greater ratio of mu to kappa agonist. If adverse effects of each constituent drug are reduced or avoided, then kappa:mu mixtures might be advantageous to mu opioids alone. PMID- 29785557 TI - Highly Sensitive Ethanol Chemical Sensor Based on Novel Ag-Doped Mesoporous alpha Fe2O3 Prepared by Modified Sol-Gel Process. AB - Mesoporous alpha-Fe2O3 has been synthesized via a simple sol-gel procedure in the presence of Pluronic (F-127) triblock copolymer as structure directing agent. Silver (Ag) nanoparticles were deposited onto alpha-Fe2O3 matrix by the photochemical reduction approach. Morphological analysis revealed the formation of Ag nanoparticles with small sizes < 20 nm onto the mesoporous structure of alpha-Fe2O3 possessing < 50 nm semi-spherical shape. The XRD, FTIR, Raman, UV vis, PL, and N2 sorption isotherm studies confirmed the high crystallinity, mesoporosity, and optical characteristics of the synthesized product. The electrochemical sensing toward liquid ethanol has been performed using the current devolved Ag/alpha-Fe2O3-modified glassy carbon electrode (GCE) by cyclic voltammetry (CV) and current potential (I-V) techniques, and the obtained results were compared with bare GCE or pure alpha-Fe2O3. Mesoporous Ag/alpha-Fe2O3 was found to largely enhance the sensor sensitivity and it exhibited excellent sensing characteristics during the precision detection of low concentrations of ethanol. High and reproducible sensitivity of 41.27 MUAmM- 1 cm- 2 at lower ethanol concentration region (0.05 to 0.8 mM) and 2.93 MUAmM- 1 cm- 2 at higher concentration zone (0.8 to 15 mM), with a limit of detection (LOD) of 15.4 MUM have been achieved. Investigation on reaction kinetics revealed a characteristic behavior of mixed surface and diffusion-controlled processes. Detailed sensing studies revealed also that the sensitivity toward ethanol was higher than that of methanol or isopropanol. With further effort in developing the synthesis and fabrication approaches, a proper utility for the current proposed protocol for fabricating a better sensor device performance is possible. PMID- 29785558 TI - Differences between first-generation and second-generation drug-eluting stent regarding in-stent neoatherosclerosis characteristics: an optical coherence tomography analysis. AB - We compared first-generation and second-generation drug-eluting stent (DES) with respect to neoatherosclerosis using optical coherence tomography or optical frequency domain imaging. In-stent restenoses in 102 first-generation and 114 second-generation DES were retrospectively assessed. Neoatherosclerosis, which was defined as the presence of lipid-laden neointima or calcification inside a stent, was observed in 33 (27.2%) and 31 (32.4%) lesions in the first-generation and second-generation DES respectively. In the first-generation DES group, the lipid length was significantly longer (5.5 +/- 3.8 vs. 3.1 +/- 2.1 mm, P = 0.0007), the lipid arc was significantly larger (324 +/- 70 degrees vs. 250 +/- 94 degrees , P = 0.002), the prevalence of a 360 degrees lipid arc was significantly greater (58 vs. 31%, P = 0.03), and the fibrous cap was significantly thinner (153 +/- 85 vs. 211 +/- 95 um, P = 0.02) compared with those in the second-generation DES group. These differences remained significant after adjusting for the age of the stent (lipid length: P < 0.001; lipid arc: P = 0.019; and fibrous cap thickness: P < 0.001). The proliferation course and stability of neoatherosclerosis over time might be superior in second-generation DES. PMID- 29785560 TI - A suggestion to introduce the diagnosis of "diffuse midline glioma of the pons, H3 K27 wildtype (WHO grade IV)". PMID- 29785562 TI - Comment on: "Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes". PMID- 29785561 TI - RepTB: a gene ontology based drug repurposing approach for tuberculosis. AB - Tuberculosis (TB) is the world's leading infectious killer with 1.8 million deaths in 2015 as reported by WHO. It is therefore imperative that alternate routes of identification of novel anti-TB compounds are explored given the time and costs involved in new drug discovery process. Towards this, we have developed RepTB. This is a unique drug repurposing approach for TB that uses molecular function correlations among known drug-target pairs to predict novel drug-target interactions. In this study, we have created a Gene Ontology based network containing 26,404 edges, 6630 drug and 4083 target nodes. The network, enriched with molecular function ontology, was analyzed using Network Based Inference (NBI). The association scores computed from NBI are used to identify novel drug target interactions. These interactions are further evaluated based on a combined evidence approach for identification of potential drug repurposing candidates. In this approach, targets which have no known variation in clinical isolates, no human homologs, and are essential for Mtb's survival and or virulence are prioritized. We analyzed predicted DTIs to identify target pairs whose predicted drugs may have synergistic bactericidal effect. From the list of predicted DTIs from RepTB, four TB targets, namely, FolP1 (Dihydropteroate synthase), Tmk (Thymidylate kinase), Dut (Deoxyuridine 5'-triphosphate nucleotidohydrolase) and MenB (1,4-dihydroxy-2-naphthoyl-CoA synthase) may be selected for further validation. In addition, we observed that in some cases there is significant chemical structure similarity between predicted and reported drugs of prioritized targets, lending credence to our approach. We also report new chemical space for prioritized targets that may be tested further. We believe that with increasing drug-target interaction dataset RepTB will be able to offer better predictive value and is amenable for identification of drug-repurposing candidates for other disease indications too. PMID- 29785559 TI - Childbirth after adolescent and young adult cancer: a population-based study. AB - PURPOSE: Annually, > 45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics. METHODS: We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression. RESULTS: Among 17,564 AYA cancer survivors, 1989 had >= 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006. CONCLUSIONS: Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years. IMPLICATIONS FOR CANCER SURVIVORS: Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis. PMID- 29785563 TI - Authors' Reply to Pires et al.: "Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes". PMID- 29785566 TI - Delineating a new feature of constitutional mismatch repair deficiency (CMMRD) syndrome: breast cancer. AB - Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive hereditary cancer condition, characterized by an exceptionally high risk of cancer, a propensity for childhood malignancies, and cutaneous features reminiscent of neurofibromatosis type 1 (NF1). We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelic MSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27. Immunohistochemistry analysis on the breast tumor tissue revealed weak MSH6 protein staining. Exome sequencing revealed a hypermutated breast tumor and an ultra-hypermutated brain tumor. Multi-gene panel testing was also performed and revealed no additional mutations which might explain the proband's early onset breast cancer. This is the first documented case of breast cancer in an individual with CMMRD syndrome. We summarize the evidence supporting the possible association between breast cancer and biallelic MMR mutations. Healthcare providers should be aware of this possible association and follow-up appropriately for suspicious breast findings. In addition, this case highlights the need for frequent central nervous system screenings due to rapid progression of brain tumors. PMID- 29785565 TI - Supplementation strategies for Nellore female calves in creep feeding to improve the performance: nutritional and metabolic responses. AB - The objective of this study was to evaluate the effects of supplementation strategy on performance, nutritional and metabolic characteristics of Nellore suckling female calves, on grazing Urochloa decumbens during the rainy-dry transition period. Forty-four Nellore female calves, averaging 147.6 +/- 1.34 kg (4 months), were used. A single supplement 20% of crude protein of dry matter was provided, consisting of daily supplement at 0.0, 0.2, 0.4, or 0.6% of body weight. A positive linear effect (P < 0.05) on final body weight and average weight gain of female calves was observed with increased supplementation. Supplementation increased consumption, in kilograms per day, of dry matter (DM), organic matter (OM), crude protein (CP), digested dry matter, and total digestible nutrients (TDN), all calculated as % of dry matter. There was no effect of supplementation on the consumption in kilograms per day of neutral detergent fiber corrected for ash and protein (apNDF) (P > 0.05). Supplementation increased, in a quadratic way, the total apparent digestibility coefficient of DM, OM, CP, apNDF, and TDN (P < 0.05). There was no effect of supplementation (P > 0.05) on non-esterified fatty acid concentrations. There was a positive linear effect (P < 0.05) of supplementation on insulin concentrations. In this study, it is concluded that linearly increasing the feeding level of a supplement with 20% crude protein (% of DM) in the range of 0.2-0.6% of body weight improves the performance, nutritional and metabolic characteristics of the animals, considering these pasture characteristics. PMID- 29785567 TI - Si-Ho Tchou: life of a legend from physiology to psychology. PMID- 29785564 TI - Helicobacter pylori Infection in Pediatric Patients: Update on Diagnosis and Eradication Strategies. AB - Helicobacter pylori infection is acquired mainly in childhood and remains an essential cause of peptic ulcer disease and gastric cancer. This article provides commentary on the last ESPGHAN/NASPGHAN guidelines and on publications made after the consensus conference of 2015. The majority of infected children are asymptomatic and pediatric studies do not support a role for H. pylori in functional disorders such as recurrent abdominal pain. The role of H. pylori infection in failure to thrive, children's growth, type I diabetes mellitus (T1DM), and celiac disease remains controversial. The diagnosis of infection should be based on upper-digestive endoscopy with biopsy-based methods. Eradication control after treatment should be based on validated non-invasive tests. Nodular gastritis is the main endoscopic finding of childhood H. pylori infection, but gastroduodenal erosions/ulcers are seen in some children, especially after 10 years of age. When indicated, eradication treatment should be given when good compliance is expected and based on the antimicrobial susceptibility profile. PMID- 29785568 TI - Theoretical Studies on InGaAs/InAlAs SAGCM Avalanche Photodiodes. AB - In this paper, we provide a detailed insight on InGaAs/InAlAs separate absorption, grading, charge, and multiplication avalanche photodiodes (SAGCM APDs) and a theoretical model of APDs is built. Through theoretical analysis and two-dimensional (2D) simulation, the influence of charge layer and tunneling effect on the APDs is fully understood. The design of charge layer (including doping level and thickness) can be calculated by our predictive model for different multiplication thickness. We find that as the thickness of charge layer increases, the suitable doping level range in charge layer decreases. Compared to thinner charge layer, performance of APD varies significantly via several percent deviations of doping concentrations in thicker charge layer. Moreover, the generation rate (G btt ) of band-to-band tunnel is calculated, and the influence of tunneling effect on avalanche field was analyzed. We confirm that avalanche field and multiplication factor (M n ) in multiplication will decrease by the tunneling effect. The theoretical model and analysis are based on InGaAs/InAlAs APD; however, they are applicable to other APD material systems as well. PMID- 29785569 TI - Association between Firearm Laws and Homicide in Urban Counties. AB - Laws related to the sale, use, and carrying of firearms have been associated with differences in firearm homicide rates at the state level. Right-to-carry (RTC) and stand your ground (SYG) laws are associated with increases in firearm homicide; permit-to-purchase (PTP) laws and those prohibiting individuals convicted of violent misdemeanors (VM) have been associated with decreases in firearm homicide. Evidence for the effect of comprehensive background checks (CBC) not tied to PTP is inconclusive. Because firearm homicide tends to concentrate in urban areas, this study was designed to test the effects of firearm laws on homicide in large, urban U.S. counties. We conducted a longitudinal study using an interrupted time series design to evaluate the effect of firearm laws on homicide in large, urban U.S. counties from 1984 to 2015 (N = 136). We used mixed effects Poisson regression models with random intercepts for counties and year fixed effects to account for national trends. Models also included county and state characteristics associated with violence. Homicide was stratified by firearm versus all other methods to test for specificity of the laws' effects. PTP laws were associated with a 14% reduction in firearm homicide in large, urban counties (IRR = 0.86, 95% CI 0.82-0.90). CBC-only, SYG, RTC, and VM laws were all associated with increases in firearm homicide. None of the laws were associated with differences in non-firearm homicide rates. These findings are consistent with prior research at the state level showing PTP laws are associated with decreased firearm homicide. Testing the effects of PTP laws specifically in large, urban counties strengthens available evidence by isolating the effects in the geographic locations in which firearm homicides concentrate. PMID- 29785571 TI - Intersectional gene inactivation: there is more to conditional mutagenesis than Cre. PMID- 29785572 TI - Differential efficiency of a begomovirus to cross the midgut of different species of whiteflies results in variation of virus transmission by the vectors. AB - Begomoviruses are important crop viral disease agents, and they are transmitted by whiteflies of the Bemisia tabaci complex. Although the transmission of begomoviruses by whiteflies has been studied for many years, the mechanisms governing differential transmission of begomoviruses by different species of the Bemisia tabaci complex remain largely unknown. Here we firstly compared the transmission efficiency of tobacco curly shoot virus (TbCSV) by four species of the B. tabaci complex and found that Asia II 1 transmitted this virus with the highest efficiency, whereas MEAM1 transmitted it with the lowest. Next, by performing quantitative analysis of virus and immune-fluorescence detection, we found that the efficiency of TbCSV to cross the midgut wall was higher in Asia II 1 than in MEAM1. Finally, we set the quantities of virions in the haemolymph to the same level in Asia II 1 and MEAM1 via injection and then compared their capacity in TbCSV transmission, and found that the difference in TbCSV transmission between them became smaller. Taken together, our findings suggest that the efficiency of a begomovirus to cross the midgut wall of a whitefly to reach the vector's haemolymph plays a significant role in determining transmission of the virus. PMID- 29785573 TI - Effect of dietary soy oil, glucose, and glutamine on growth performance, amino acid profile, blood profile, immunity, and antioxidant capacity in weaned piglets. AB - Weaning stress results in gastrointestinal dysfunction and depressed performance in pigs. This study aimed to investigate the effect of soy oil, glucose, and glutamine on the growth and health of weaned piglets. Compared with those in the glutamine group, piglets in the glucose and soy oil groups had greater average daily gain, average daily feed intake, and gain: feed ratio from day 0 to 14, and gain: feed ratio for the overall period. There were no differences with regard to serum amino acids among the three groups on day 14, except glycine and threonine. The serum concentration of histidine, serine, threonine, proline, and cysteine was the highest in the glutamine group, while the content of glycine and lysine in the soy oil group on day 28 was the highest among all groups. Piglets fed with glutamine had greater serum glucose and creatinine on day 14, high-density lipoprotein on day 28, and serum IgG and IgM on day 28. Piglets in the glutamine group demonstrated lower serum total superoxide dismutase on day 14 and 28; however, they demonstrated higher total superoxide dismutase and total antioxidant capacity in the duodenum and ileum on day 14. Weaned pigs supplemented with glucose or soy oil demonstrate better growth performance possibly due to their enhanced feed intake, whereas those supplemented with glutamine may have improved immunity and intestinal oxidative capacity. PMID- 29785570 TI - Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer. AB - Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in patients who received <=1 line of therapy for advanced BTC was conducted after determination of the maximum tolerated dose in this Phase 1 trial. Patients received binimetinib 60 mg twice daily. The primary objectives were to characterize the safety profile and pharmacokinetics of binimetinib in advanced BTC. Secondary objectives included assessment of clinical efficacy, changes in weight and lean body mass, and pharmacodynamic effects. Tumor samples were assessed for mutations in relevant genes. Results Twenty-eight patients received binimetinib. Common adverse events (AEs) were mild, with rash (82%) and nausea (54%) being most common. Two patients experienced grade 4 AEs, one generalized edema and the other pulmonary embolism. The pharmacokinetics in this patient population were consistent with those previously reported (Bendell JC et al., Br J Cancer 2017;116:575-583). Twelve patients (43%) experienced stable disease and two had objective responses (1 complete response, 1 partial response) per Response Evaluation Criteria in Solid Tumors and stable metabolic disease by positron emission tomography/computed tomography. Most patients (18/25; 72%) did not have KRAS, BRAF, NRAS, PI3KCA, or PTEN mutations, nor was there correlation between mutation status and response. The average non-fluid weight gain was 1.3% for lean muscle and 4.7% for adipose tissue. Conclusion Binimetinib was well tolerated and showed promising evidence of activity in patients with BTC. Correlative studies suggested the potential for binimetinib to promote muscle gain in patients with BTC. PMID- 29785574 TI - In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization. AB - The purpose of conducting the present research work was to develop resveratrol nanostructured in situ gel for the treatment of Alzheimer's disease. Resveratrol loaded lipid carrier was prepared by melt emulsification-probe sonication method, and the final product was evaluated for particle size (132 +/- 11.90 nm), polydispersity index (0.209 +/- 0.005), zeta potential (- 23 +/- 3.79 mV), drug loading (9.26 +/- 3.79%), and entrapment efficiency (74 +/- 11.40%). Following incorporation of the resveratrol nanostructured lipid carrier in gellan gum and xanthan gum, in situ gel was formulated and characterized. The optimized in situ gel showed fivefold higher permeation across the nasal mucosa as compared to resveratrol suspension-based in situ gel. Finally, optimized in situ gel was evaluated using in vivo pharmacodynamic study by the scopolamine-induced amnesia model in rats using Morris Water Maze test. It showed significant improvement in memory function in rats treated with optimized in situ gel as compared to orally administered resveratrol suspension. The enhanced permeation across nasal mucosa and improved memory function suggest that the resveratrol nanostructured lipid carrier-based in situ gel could be an effective and promising approach for the treatment of Alzheimer's disease. PMID- 29785575 TI - Vehicular stress a cause for heavy metal accumulation and change in physico chemical characteristics of road side soils in Pahalgam. AB - In an effort to determine vehicular impact on soil quality, soil samples were collected from three different zones (Pahalgam, Batakote, and Chandanwari) in Pahalgam forest ecosystem. Results showed that a significant decrease in moisture content, organic carbon, available nitrogen, and potassium was observed in nearby road side soils. However, pH was observed to be on neutral side and available phosphorus recorded high concentration. The concentration of heavy metals Pb2+, Cu2+, Zn2+, Ni2+, and Cd2+ estimated was also significantly high. Furthermore, concentration of Pb2+ at high vehicular load subzones was observed to be highest (1.168 mg/Kg) followed by Zn2+ (0.896 mg/Kg), Ni2+ (0.649 mg/Kg), Cu2+ (0.415 mg/Kg), and Cd2+ (0.079 mg/Kg). An inter-zone analysis revealed that the concentration of the heavy metals (Pb2+ > Ni2+ > Cd2+) was observed to follow the trend, Z-I > Z-II > Z-III. Variation along the temporal gradient and the impact on soil qualities were notably higher in summer. Vehicular pollution to a great extent impacts physico-chemical characteristics and more interestingly adds substantial concentration of heavy metals in soils. PMID- 29785576 TI - Prognostic Impact of the Components of Progressive Disease on Survival After First-Line Tyrosine Kinase Inhibitor Therapy for Metastatic Renal Cell Carcinoma. AB - BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors (RECIST) classification, progressive disease (PD) is defined as target lesion growth (TLG), unequivocal non-target lesion growth (NTLG), or new lesion appearance (NLA). The prognostic impact of the components of PD in tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC) remains unknown. OBJECTIVE: We retrospectively evaluated the prognostic impact of these PD components on survival in patients with mRCC after first-line TKI therapy. PATIENTS AND METHODS: Patients were divided into three groups (TLG, NTLG, and NLA) based on the components of PD. Progression-free survival (PFS) and overall survival (OS) after first-line TKI therapy were compared between groups using the Kaplan-Meier method and log-rank test. The predictive impact of the PD components was evaluated using multivariate analyses. RESULTS: Among the 116 patients included, 80 (69.0%) had TLG, 18 (15.5%) NTLG, and 69 (58.6%) NLA. The mean PFS and OS were shorter for patients with TLG than those without TLG (PFS, 7.1 vs. 11.6 months, p = 0.0071; OS, 18.2 vs. 25.5 months, p = 0.0091). TLG was an independent predictor of PFS (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.02-2.51; p = 0.0395) and OS (HR, 1.67; 95% CI, 1.02-2.83; p = 0.040). NTLG and NLA were not associated with survival. CONCLUSIONS: In this retrospective single-center study, patients with TLG had poor survival after first-line TKI therapy for mRCC. Thus, individual components of PD influence patient prognosis. PMID- 29785577 TI - Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. AB - Atezolizumab (TECENTRIQTM), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy. PMID- 29785579 TI - 56th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV 2018). PMID- 29785578 TI - Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine. AB - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behind PACAP-induced migraine attacks, but also to develop antimigraine drugs targeting the PACAP receptors Here, we aim to review the transport ability of PACAP across the BBB. METHODS: We performed a systematic literature search on PubMed to identify studies reporting original data on PACAP and BBB. The search was finalized in July 2017. RESULTS: The literature search identified 96 papers of which 11 contained relevant data. In addition, two papers were known to be relevant and were included. A total of 13 papers studies were included in the final analysis. Preclinical studies (n = 10) suggest the existence of specific PACAP transport systems across the BBB, while human PACAP studies failed to show vasodilator effect of PACAP on the cerebral arteries from the lumen (n = 3). CONCLUSION: PACAP38 is transported over the BBB actively, while PACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms are either rapidly degraded or efflux back from brain to blood. Thus, a direct central action of the PACAPs is unlikely. This is supported by studies showing selective PACAP effect on extra cerebral arteries. PMID- 29785581 TI - Anti-JC virus antibody sera positivity and index value among patients with multiple sclerosis may be correlated with age, sex, and area of residence. AB - Anti-JC virus (JCV) antibody index is the predictive factor of progressive multifocal leukoencephalopathy (PML) for multiple sclerosis (MS) patients treating with natalizumab. The aim of this study is to evaluate the prevalence of anti-JCV antibody positivity and index among Iranian patients who are the candidate for natalizumab and its correlation with their demographic data and previous therapies. A cross-sectional design was assessed for receiving anti-JCV antibody test results between January 2014 and December 2016. Demographic data and disease characteristics were also obtained. Statistical analysis and logistic regression were done using SPSS. Among 803 MS patients that were observed, the prevalence of anti-JCV antibody positivity was 67.9% (mean of index = 2.23 +/- 1.16) and 67.6% of positive patients had an index >= 1.5. Males were more antibody positive than females (81.7 and 64% respectively; significance (sig.) < 0.001, OR = 2.51, CI 1.65-3.81). The rate of positivity was lower in patients under the age of 18. Patients who lived in cold regions had significantly more prevalence of positivity (Num. = 403; sig. = 0.043 and OR = 1.86; CI 1.02-3.39) and with higher rate of index >= 1.5 (sig. = 0.017; OR = 3.99, CI 1.79-8.88). Disease onset age between 28 and 37 years were more positive compared to 18-27 years (N = 480; sig. = 0.02; OR = 1.85, CI 1.09-3.14). Age, male gender, onset age, and cold area of residency significantly influenced anti-JCV antibody sera positivity. Only age of onset and cold area of residency were related to the index. No significant difference was observed between type, dosage, and duration of previous immunosuppressant drugs and anti-JCV antibody positivity and index value. PMID- 29785580 TI - A comprehensive review and meta-analysis of risk factors for statin-induced myopathy. AB - PURPOSE: To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta analysis. METHODS: This meta-analysis was done through four phases: (1) Identification of the relevant primary literature; (2) abstract screening using inclusion and exclusion criteria; (3) detailed review and data extraction; and (4) synthesis and statistical analysis. RESULTS: Out of 44 papers analyzed from 836 papers searched from MEDLINE, 18 different potential risk factors were collected, divided into three categories: three demographics (11 papers), ten clinical factors (31 papers), and five pharmacogenetics/biomarkers (12 papers). Risk factors significant for myopathy and/or rhabdomyolysis included age, gender, diabetes, renal impairment, cardiovascular disease, certain interacting drugs, and mutations of the SLCO1B1 gene, which encodes a transporter protein in the liver. Several factors, such as gender, race, cardiovascular disease, and the GATM gene, which encodes a protein for creatine synthesis, appeared to be protective in terms of the outcomes of interest. CONCLUSIONS: This comprehensive assessment of risk factors can help support clinicians in reducing the incidence of SIM in their patient population on statins. PMID- 29785582 TI - Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients. AB - In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients. PMID- 29785583 TI - The effect of delayed anti-NMDAR encephalitis recognition on disease outcome. AB - Anti-NMDA receptor encephalitis is an acute form of brain inflammation that is potentially lethal but has a high probability for recovery with treatment. Although the clinical picture of anti-NMDAR encephalitis is usually recognizable due to its relatively well-known symptoms, the disorder can sometimes present itself in an unpredictable and atypical way. In this case report, we wish to present the influence of different delay times prior to the establishment of diagnosis. Thus, our first patient was diagnosed with anti-NMDAR encephalitis 4 years after the initial symptoms, the second one after 8 years, and the third one after 13 months. The outcomes of the three presented patients indicate the importance of being aware of many clinical presentations of this disorder, as its early diagnosis greatly affects the outcome and may reduce permanent damage, especially in cognitive functions. PMID- 29785585 TI - Poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser-assisted hair removal: about 3 cases. AB - BACKGROUND: Eutectic mixtures of lidocaine and prilocaine are used during painful dermatological procedures. Poisoning is rarely reported in adults. MATERIAL AND METHOD: We report three cases of women who experienced lidocaine and prilocaine poisoning after laser-assisted hair removal. Plasma levels of local anesthetics were assayed by a fully validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. CASE REPORTS: The rules of application of the anesthetic cream were observed apart from the maximum dose and/or maximum surface area. One patient applied a higher dose than the maximum recommended dose (140 instead of 60 g) and all patients failed to comply with the maximum recommended surface area (600 cm2). The patients presented an unusual clinical pattern as compared with other local anesthetics overdose: signs of cardiac toxicity with no ECG changes or arrhythmia, neurological toxicity without seizures or coma, and methemoglobinemia. DISCUSSION: Health authorities should publish explicit recommendations targeting users and prescribers with particular emphasis on the maximal surface area of application. PMID- 29785584 TI - Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health. AB - The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV infected patients. PMID- 29785586 TI - Suicide by plastic bag suffocation combined with the mixture of citric acid and baking soda in an adolescent. AB - We describe a case of suicidal asphyxiation using a plastic bag combined with carbon dioxide (CO2) gas. A 20-year-old male, whose head was covered with a plastic bag, was found dead in his room. In the plastic bag, there were two glass made cups containing liquid-like substance. Through crime scene investigation by police staffs, a bottle of citric acid and a box of baking soda were also discovered in his room. The forensic autopsy revealed that there were neither lesions nor injuries in all of the organs. Moreover, any drugs and poisons could not be detected in blood samples. Based on autopsy findings and crime scene investigation, the cause of death was diagnosed as acute asphyxia due to CO2 intoxication by the mixture of citric acid with baking soda in the plastic bag. To the best of our knowledge, there are no medical literatures describing plastic bag suffocation combined with CO2 gas generated from citric acid and baking soda, which has been widely distributed as suicidal means through websites. This case report promotes forensic pathologists and medical coroners to emphasize that the Internet has a crucial role on a source of suicidal information or a promoter of suicide all over the world. PMID- 29785587 TI - A study on the use of strain-specific and homologous promoters for heterologous expression in industrial Saccharomyces cerevisiae strains. AB - Polymorphism is well known in Saccharomyces cerevisiae strains used for different industrial applications, however little is known about its effects on promoter efficiency. In order to test this, five different promoters derived from an industrial and a laboratory (S288c) strain were used to drive the expression of eGFP reporter gene in both cells. The ADH1 promoter (P ADH1 ) in particular, which showed more polymorphism among the promoters analyzed, also exhibited the highest differences in intracellular fluorescence production. This was further confirmed by Northern blot analysis. The same behavior was also observed when the gene coding for secreted alpha-amylase from Cryptococcus flavus was placed under the control of either P ADH1 . These results underline the importance of the careful choice of the source of the promoter to be used in industrial yeast strains for heterologous expression. PMID- 29785588 TI - Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Synoviocytes by Enhancing the NF-kappaB/P65 Pathway in Rheumatoid Arthritis. AB - Src-associated substrate during mitosis of 68 KDa (Sam68), also known as KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1), is the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Previous studies have indicated that Sam68 regulates nuclear transcription factor kappa B (NF-kappaB) to mediate inflammation. In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the control group. Immunoflourescent staining demonstrated that Sam68 co localized with fibroblast-like synoviocytes (FLS) of RA patients. Additionally, the expression of Sam68 in FLS was increased by tumor necrosis factor (TNF)-alpha stimulation, in a time-dependent manner. Upon TNF-alpha treatment, Sam68 translocated from the cytoplasm to the nucleus where it interacted with the p65 subunit of NF-kappaB, as examined by immunoprecipitation and immunofluorescent staining assay. Furthermore, inhibiting the expression of Sam68 by siRNA significantly suppressed the TNF-alpha-induced expression of interleukin (IL)-6, and matrix metalloproteinase (MMP)-1, reduced the proliferation, migration, and invasion, and markedly decreased the phosphorylation of P65 and IkappaBalpha in FLS. Collectively, our findings suggested that Sam68 contributed to the production of inflammatory cytokines, proliferation, migration, and invasion of RA FLS through the NF-kappaB P65 signal transduction pathway and underscored the importance of Sam68 in the inflammation process of RA. PMID- 29785589 TI - A novel technology for 3D knee prosthesis planning and treatment evaluation using 2D X-ray radiographs: a clinical evaluation. AB - PURPOSE: To present a clinical validation of a novel technology called "3X" which allows for 3D prosthesis planning and treatment evaluation in total knee arthroplasty (TKA) using only 2D X-ray radiographs. MATERIALS AND METHODS: After local institution review board approvals, 3X was evaluated on 43 cases (23 for preoperative planning and 20 for postoperative treatment evaluation). All the patients underwent CT scans according to a standard protocol. The results measured on the CT data were regarded as the ground truth. Additionally, two X ray images were acquired for each affected leg and were used by 3X technology to derive patient-specific measurements of the leg. In total, we compared seven parameters for planning TKA and five parameters for postoperative prosthesis alignment. RESULTS: Our experimental results demonstrated that the mean distances between the surface models reconstructed from 2D X-rays and the associated surface models obtained from 3D CT data were smaller than 1.5 mm. The average differences for all angular parameters were smaller than [Formula: see text]. In over 78% cases 3X technology derived the same femoral component size as the CT-based ground truth and this value went down to 70% when 3X technology was used to predict the size of tibial component. CONCLUSION: 3X is a technology that allows for true 3D preoperative planning and postoperative treatment evaluation based on 2D X-ray radiographs. PMID- 29785590 TI - Clinical application of a minimally invasive cement-augmentable Schanz screw rod system to treat pelvic ring fractures. AB - PURPOSE: The purpose of this study is to analyze the results using the USS fracture MIS system (DePuy Synthes) to treat instable pelvic ring fractures. As its outstanding feature, it is the only Schanz screw and rod system at present that combines angular stability, perforation/fenestration of the screws for cement-augmentation, a variable screw length, and a large screw diameter. MATERIALS AND METHODS: Retrospective investigation of 134 pelvic ring fractures treated in 2012-2013. Twenty-five patients obtained the abovementioned implant. Besides baseline characteristics of the included patients and the surgical procedure, a clinical/radiological follow-up of six months was analyzed. RESULTS: Dividing the collective into two groups, I high-energy trauma and II fragility fracture of the pelvis, the following results were recorded: group I: ten patients, six male, age 48.4 +/- 19.7 years. Mean ISS 41 +/- 22.5, fracture classification: AO/OTA type 61 B1/C1/C3 = 1/5/4. Operative treatment: three transiliac internal fixator, seven iliolumbar fixation, one implant was cement augmented. Group II: 15 patients, 14 female, age 77.5 +/- 10.1 years. Fracture classification according to Rommens: FFPII/III/IV = 6/1/8. Operative treatment: eight transiliac internal fixator, seven iliolumbar fixation, 14 implants were cement-augmented. Overall surgical side complications: 16%. Radiological examination: correct positioning of all ilium screws. Follow-up after six month (16 patients): all showed fracture consolidation. One ilium screw was broken close to the connecting clamp. CONCLUSION: The investigated Schanz screw rod system is a suitable implant to broaden the established procedures to stabilize dorsal pelvic ring fractures. TRIAL REGISTRATION: The study is registered at the Clinical Trial Registry University of Regensburg (Number Z-2017-0878-3). PMID- 29785591 TI - Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral head. AB - PURPOSE: Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. METHODS: Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. RESULTS: The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = - 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). CONCLUSIONS: The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH. PMID- 29785592 TI - Methylmercury and diphenyl diselenide interactions in Drosophila melanogaster: effects on development, behavior, and Hg levels. AB - Methylmercury (MeHg) is a highly toxic environmental pollutant which binds with a high affinity to selenol groups. In view of this, seleno-compounds have been investigated as MeHg antidotes. In the present study, we evaluated the effects of the co-exposure to MeHg and the seleno-compound diphenyl diselenide (PhSe)2 on Drosophila melanogaster. We measured the survival rate, developmental survival, locomotor ability, reactive oxygen species (ROS) production, and Hg levels in D. melanogaster exposed to MeHg and/or (PhSe)2 in the food. Exposure to MeHg caused a reduction in the survival rate, developmental survival, and locomotion in D. melanogaster. In addition, MeHg increased the ROS production and mercury levels in flies. The co-exposure to MeHg and (PhSe)2 did not prevent the toxic effects of MeHg in D. melanogaster. On the contrary, the co-exposure enhanced the toxic effects on the locomotor ability and developmental survival. This effect may be explained by the fact that the co-exposure increased the Hg levels in body when compared to flies exposed only to MeHg, suggesting that MeHg and (PhSe)2 interaction may increase Hg body burden in D. melanogaster which could contribute for the increased toxicity observed in the co-exposure. PMID- 29785593 TI - A study of biochemical route on construction of waste battery ferrite applying for nickel removal. AB - Mn-Zn ferrite (Mn1 - xZnxFe2O4, x = 0.2, 0.4, 0.6, and 0.8) nanomaterials were prepared by bioleaching and hydrothermal synthesis from waste Zn-Mn batteries. The materials were characterized by XRD, SEM, BET, VSM, CEC, and isoelectric point. It turned out when x = 0.4, synthesized Mn-Zn ferrite had best performance which was nanoferrite crystal structure with a specific surface area that reached 37.77 m2/g, the saturation magnetization was 62.85 emu/g, and isoelectric point and the CEC value were 7.33 and 43.51 mmol/100 g, respectively. In addition, the adsorption characteristics on Ni2+ were explored. The results of experiment suggested that data was more in line with the Freundlich model compared with Langmuir and Dubinin-Radushkevich isotherm models. Kinetics studies showed that pseudo-second-order kinetics was more suitable for describing the Ni2+ adsorption process where the maximum theoretical adsorption quantity was 52.99 mg/g. Thermodynamic parameters indicated the adsorption process can be spontaneous as an endothermic reaction, and warming was advantageous to adsorption. Besides, the adsorbent could be reused for six cycles with high removal efficiency. The magnetic and adsorptive properties of the adsorbent were promising, which had a high application value. Graphical abstract Fabrication process of nanometer ferrite by biological technology and hydrothermal synthesis for removal of Ni2. PMID- 29785594 TI - Attitudes and behaviour towards construction waste minimisation: a comparative analysis between China and the USA. AB - With the spread of the concept of sustainable development, people have gained awareness about the problem of massive illegal dumping of construction waste. In this research, a questionnaire survey was carried out in the USA and China. The results indicated the following. (1) Workers in both the countries had positive minimisation attitudes, and the attitude of Chinese construction workers was not significantly different from that of American construction workers. Furthermore, their average values were 3.9 and 4.07, respectively. (2) Business owners had a poor understanding of the obligations that should be fulfilled by contractors and construction workers, which greatly reduced (a) construction workers' and contractors' motivation to implement waste minimisation management and (b) the benefit-driven effect. (3) In terms of perceived behavioural control, Chinese construction workers had poorer minimisation technologies and knowledge than American construction workers, and it was very difficult for them to implement construction waste minimisation. The research conclusions and relevant suggestions may be used to improve the construction waste minimisation behaviour and awareness of Chinese people and promote China's construction waste minimisation management. PMID- 29785595 TI - A preliminary investigation on water quality of coalbed natural gas produced water for beneficial uses: a case study in the Southern Qinshui Basin, North China. AB - Coalbed natural gas (CBNG) is an important unconventional natural gas resource with large reserves in China and receives much attention these years. The CBNG production is accomplished by extracting large volumes of produced water from the aquifer. The CBNG-produced water is commonly managed by discharging into nearby disposal ponds in the Southern Qinshui Basin (SQB), which provides an opportunity for water source for nearby irrigation, livestock, wildlife, and human drinking water. However, utilization of this nontraditional water source in the SQB is hindered by limited knowledge of water quality, practically oxidation/reduction potential (OPR), electrical conductivity (EC), sodium adsorption ration (SAR), and trace element chemistry data. The objective of this study was to collect CBNG produced water samples at discharge points in the SQB and investigate their water quality principally, including physicochemical parameters, major ions parameters, and trace element parameters. Discharge points were sampled from five main CBNG blocks in the SQB including SZ, ZZ, FZ, CZ, and PZ blocks from July 31, 2013 to August 11, 2014. A composite geochemical data was created with the test results from 145 produced water samples, resulting in information on 40 constituents/parameters. The resulting constituents/parameters were compared to common water use criteria of China to determine possible beneficial uses. Results suggest that the CBNG-produced waters from SQB are characterized by dominated Na HCO3 type waters, with approximately 12% Na-SO4 and Na-Cl type waters. The observed TDS ranges from 615 to 4376 mg/L with 91% are less than 3000 mg/L, and Na+ and HCO3- are the dominating determinants of the TDS content. The EC values vary from 930 to 3844 MUS/cm, ranging from class 3 to class 5 based on the suitability for irrigation. The CBNG-produced waters in SQB generally exhibit higher SAR values (avg. 41.98). Among the 25 detected trace elements in CBNG produced waters from SQB, elements of environmental concerns include aluminum, iron, selenium, barium, manganese, nickel, and plumbum because their concentrations exceed the related Chinese regulatory standards for human drinking. The commonly constituents exceeding standards for human drinking water, livestock water, poultry water, and irrigation water include fluorinion, pH, and TDS. Besides, targeted reduction of SAR and EC also needs to be treated for most of the produced waters if used for irrigation. In contrast, the CBNG-produced waters in SQB are the most suitable for livestock water, because approximately 88% of the CBNG-produced waters are suitable for livestock drinking if the fluorinion is reduced. PMID- 29785596 TI - Biochar reduces nitrate level in red beet. AB - Impacts of red beet consumption both on human and animal health are subject of intense research. In particular, products that are not heat-processed contain plethora of bioactive compounds that hold promise against numerous degenerative and aging-associated diseases. However, high level of nitrates (typically more than 2 g NO3- kg-1) whose health effects are perceived with reasoned objections counterbalance these benefits. Following the above, from a certain level, the increased consumption of red beet has contrary impacts, creating a limiting factor not only from the economic point of view but also in terms of beneficial compounds intake. Reduction of NO3- levels (- 35%) has been achieved by soil amendment via increased doses of biochar. The data obtained indicates that the mechanism can be explained as follows. The soil improvement reduces soil density, increases soil temperature, improves water retention, and other prerequisites for increased activity of soil microorganisms. Accelerated metabolism of soil biota turned more nitrogen from fertilizers into organic forms. Hence, less mineral nitrogen is left for red beet intake. PMID- 29785597 TI - Removal of methylene blue dye from aqueous solution using immobilized Agrobacterium fabrum biomass along with iron oxide nanoparticles as biosorbent. AB - A nano-biosorbent for the removal of methylene blue (MB) was prepared by encapsulating iron oxide nanoparticles (NPs) and Agrobacterium fabrum strain SLAJ731, in calcium alginate. The prepared biosorbent was optimized for the maximum adsorption capacity at pH 11, 160 rpm, and 25 degrees C. Adsorption kinetics was examined using pseudo-first-order, pseudo-second-order, and intra particle diffusion (IPD) models. The kinetic data agreed to pseudo-second-order model indicating chemisorption of MB, which was also explained by FTIR analysis. The adsorption rate constant (k2) decreased and initial adsorption rate (h, mg g 1 min-1) increased, with an increase in initial dye concentration. The dye adsorption process included both IPD and surface adsorption, where IPD was found to be a rate-limiting step after 60 min of adsorption. The adsorption capacity was found to be 91 mg g-1 at 200 mg L-1 dye concentration. Adsorption data fitted well to Freundlich isotherm; however, it did not fit to Langmuir isotherm, indicating adsorbent surfaces were not completely saturated (monolayer formed) up to the concentration of 200 mg L-1 of MB. Thermodynamic studies proposed that the adsorption process was spontaneous and exothermic in nature. Biosorbent showed no significant decrease in adsorption capacity even after four consecutive cycles. The present study demonstrated dead biomass along with NPs as a potential biosorbent for the treatment of toxic industrial effluents. PMID- 29785599 TI - Activated carbon as catalyst for microwave-assisted wet peroxide oxidation of aromatic hydrocarbons. AB - This paper addresses the removal of four aromatic hydrocarbons typically found in petrochemical wastewater: benzene (B), toluene (T), o-xylene (X), and naphthalene (N), by microwave-assisted catalytic wet peroxide oxidation (MW-CWPO) using activated carbon (AC) as catalyst. Under the studied conditions, complete pollutant elimination (B, 1.28 mM; T, 1.09 mM; X, 0.94 mM; and N, 0.78 mM) was achieved, with more than 90% TOC removal after only 15-min reaction time, working at 120 degrees C, pH0 = 3, AC at 1 g L-1, and H2O2 at the stoichiometric dose. Furthermore, in the case of toluene, naphthalene, and xylene, the hydroxylation and breakdown of the ring is very rapid and toxic intermediates were not detected. The process follows two steps: (i) pollutant adsorption onto AC followed by (ii) adsorbed compounds oxidation. Thus, MW-CWPO with AC as catalyst appears a promising way for a fast and effective process for B, T, X, and N removal in aqueous phase. PMID- 29785598 TI - A case study on the occurrence, transport, and fate of mercury species in a sewage treatment plant in Jiaozuo, China. AB - Occurrence and fate of sewage- and sludge-borne total mercury (THg) and methylmercury (MeHg) have received little attention, although they might be an important component of the global Hg inventory. To address the knowledge gap, sewage and sewage sludge (SS) samples were collected from a secondary municipal sewage treatment plant (MSTP) located in Jiaozuo, China. Total Hg in the raw sewage varied between 95.3 ng/L and 1.2 * 103 ng/L, while MeHg occurred in the sewage within ranges of 2.7-21.3 ng/L. On average, 93.4% of THg and 89.1% of MeHg were removed from the raw sewage by the MSTP. Around 80% of net THg input into the MSTP was transported to the SS, while 80% of net MeHg input was decomposed during the treatment processes. Thus, MSTPs would be regarded as an important sink of sewage-borne THg and MeHg. On the other hand, MeHg widely occurred in the SS, with concentrations between 7.2 and 10.2 ng/g, accounting for 0.2% of the corresponding THg contents in the SS. Occurrence of THg and MeHg in the SS indicated that SS would be a significant source of MeHg and THg to the environment. PMID- 29785600 TI - Performance and microbial community of CIC anaerobic reactor treating food waste under different grease contents and inner circulation ratio. AB - High concentrations of grease easily inhibit anaerobic digestion. The stability of the process and microbial responses in the controlling internal circulation (CIC) reactor used for treating food waste were investigated under different grease contents and inner circulation ratios. Results showed that at the grease content of 1 g/L, the removal rates of 94% and 86-93% were achieved for chemical oxygen demand (COD) and NH3-N, respectively. In contrast, when the grease content increased to 7 g/L, removal rates for COD and NH3-N significantly decreased to 42.8 and 10%, respectively. In the three-dimensional excitation and emission matrix (3D-EEM) spectra of LB-EPS (loosely bound extracellular polymeric substances), the fluorescence intensity of coenzyme F420 was weakened in the granular sludge, and the fluorescence peak of aromatic protein disappeared in the TB-EPS (tightly bound EPS). The activity and stability of the granular sludge deteriorated with increasing grease content, in this case at 7 g/L. However, when the inner cycle ratio was increased to 4, the removal rate of COD and NH3-N increased to about 70 and 76%, respectively. The adverse effects of grease could be decreased by increasing the inner cycle ratio. When the grease content increased from 1 to 7 g/L, the abundance of Methanofollis increased from 9.93 to 46.41%, while Methanothrix abundance was reduced from 18.4 to 3.07%. It could indicate that Methanothrix was sensitive to high grease content. PMID- 29785601 TI - Alteration in apoptotic rate of testicular cells and sperms following administration of Bisphenol A (BPA) in Wistar albino rats. AB - The aim of the study was to evaluate the effect of Bisphenol A [BPA] widely used as a plasticizer in the formation of polycarbonate plastics and epoxy resins, exposure causing alteration in apoptosis rate, and protective effect of Vitamin E when supplemented with BPA orally. Adult male Wistar albino rats aged 3 months were randomly divided into seven groups: control (olive oil treated) BPA-treated (dose 5, 50,100 MUg/100gmBW) and Vitamin E intervention group (dose 5, 50, 100 MUg/100gmBW BPA+ Vitamin E dose 4 mg/100gmBW). Animals were sacrificed 3 months later, and blood and tissue samples were collected. Apoptotic changes were analyzed in epididymal spermatozoa and testis tissue by binding of annexin V apoptotic biomarker. A significant decline in the weight of testis, testosterone level, and sperm count was observed. Histopathological and apoptotic changes were observed in testis tissue. In epididymal sperms, the early apoptotic cells were observed by staining of annexin V-conjugated FITC and PI green fluorescence in spermatozoa head which indicated the damage of membrane and late apoptotic cells. These changes reduced significantly in Vitamin E-treated groups though were not found to be comparable to control animals. All these changes were attributed to disrupted spermatogenesis that would interfere with sperm formation. Thus, the study infers that BPA affects the apoptosis process in the testis and epididymal sperm that would interfere with its function and contribute to infertility, whereas Vitamin E-supplemented dose has a protective effect towards these changes, indicating its role in improving male fertility. PMID- 29785602 TI - Feasibility study of cadmium adsorption by palm oil fuel ash (POFA)-based low cost hollow fibre zeolitic membrane. AB - Palm oil fuel ash (POFA) is an agricultural waste which was employed in this study to produce novel adsorptive ceramic hollow fibre membranes. The membranes were fabricated using phase inversion-based extrusion technique and sintered at 1150 degrees C. The membranes were then evaluated on their ability to adsorb cadmium (Cd(II)). These membranes were characterised using (nitrogen) N2 adsorption-desorption analysis, field emission scanning electron microscopy energy-dispersive X-ray spectroscopy (FESEM-EDX) mapping, X-ray fluorescence (XRF), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses while adsorptivity activity was examined by batch adsorption studies. The adsorption test results show that the quantity of hollow fibre used and water pH level significantly affected the adsorption performance with the 3 fibre membrane yielding 96.4% Cd(II) removal in 30 min equilibrium time at pH 7. These results are comparable to those reported by other studies, and hence demonstrate a promising alternative of low-cost hollow fibre adsorbent membrane. Graphical abstract Figure of FESEM image of the hollow fibre, proposed mechanism and the graph of percentage removal of Cd(II) using POFA. PMID- 29785603 TI - Trace and macro elements in the femoral bone as indicators of long-term environmental exposure to toxic metals in European brown bear (Ursus arctos) from Croatia. AB - We explored the long-term accumulation of aluminium, strontium, cadmium and lead in the compact and trabecular bone of the femoral epiphysis, metaphysis and diaphysis in 41 brown bears (Ursus arctos) from Croatia. Also, we assessed their influence on macro and trace elements (sodium, magnesium, phosphorus, potassium, calcium, manganese, iron, cobalt, copper, zinc and barium) in bears' bone. There were no sex differences in element levels in general, while age was associated with bone length and levels of all elements, except for cadmium. Elements had different levels depending on the part of the bone sampled. More pronounced differences were observed between the compact and trabecular regions, with higher levels of majority of elements found in compact bone. Moderate to high associations (Spearman coefficient, rS = 0.59-0.97) were confirmed between calcium and potassium, magnesium, phosphorus, manganese, cobalt, zinc, strontium and lead. Lead levels in the bone were below those known to cause adverse health effects, but in 4 of 41 animals they exceeded baseline levels for domestic animals. The femoral bone of the brown bear reflected the accumulative nature of lead and strontium well, as it did the impairment of bone-forming essential element levels associated with these two elements. However, the distribution pattern of elements along the bone was not uniform, so additional care should be taken when choosing on the part of the bone sampled. PMID- 29785604 TI - Cadmium phytoextraction potential of king grass (Pennisetum sinese Roxb.) and responses of rhizosphere bacterial communities to a cadmium pollution gradient. AB - Screening for tolerant and high biomass producing plants is important for phytoextraction efforts in remediating agricultural soils contaminated by heavy metals. We carried out a greenhouse experiment involving a soil cadmium (Cd) concentration gradient (0.1, 0.5, 1, 2, 4, and 8 mg kg-1) to assess growth and phytoextraction capacity of king grass (Pennisetum sinese Roxb.) in soils contaminated by Cd and to explore changes in diversity and structure of rhizosphere soil bacterial communities in response to long-term Cd pollution. A significant positive relationship was observed between Cd concentrations in P. sinese stems, leaves, and roots and soil Cd concentration. The highest Cd concentrations in shoots and roots were 28.87 and 34.01 mg kg-1, respectively, at 8 mg kg-1of soil Cd supply. Total extraction amounts of Cd in P. sinese were 0.22 1.86 mg plant-1 corresponding to treatment with 0.5-8 mg kg-1 Cd. Most of the Cd was stored in shoots, and the largest accumulation was 1.56 mg plant-1 with 54.02 g dry shoot weight. After phytoextraction, changes in rhizobacterial community composition were found with different levels of Cd application, whereas there were no clear trends in diversity and richness. Results of this study show the feasibility of P. sinese in accumulating Cd and provide support for its application in remediation of soil moderately contaminated by Cd. PMID- 29785606 TI - Where did Roman masons get their material from? A preliminary DRIFTS/PCA investigation on mortar aggregates from X Regio buildings in the Veneto area (NE Italy) and their potential sources. AB - In this work, preliminary results are presented of an ongoing investigation aiming to identify the possible material sources employed by ancient Romans in their building activity in the X Regio, the European region corresponding to present north-eastern Italy and Istria (Croatia and Slovenia). The 63-420 MUm fraction of the aggregate component recovered from eleven mortar fragments of buildings located in the Veneto area (in or close to Lio Piccolo, Vicenza, and Padua) is studied by diffuse reflection infrared Fourier transform spectroscopy and compared through principal component analysis to samples collected from local potential sources of raw materials. In this regard, the investigated samples from Lio Piccolo present a distinctive complexity, being this site located within the Venice lagoon, an area that has since been undergoing dramatic changes both due to natural and anthropic causes. The Vicenza and Padua sites were considered for comparison sake because they are or were located close to two rivers, the Bacchiglione and the Brenta, that in ancient times flowed into the Venice lagoon. As expected, from the exploratory investigation reported here, no firm conclusions can be obtained for the mortar samples collected in Lio Piccolo, whereas the likely provenance of the aggregate component of the samples from Vicenza and Padova from the Bacchiglione and the Brenta riverbeds, respectively, is confirmed. PMID- 29785605 TI - Selection of inactivation medium for fungal spores in clinical wastes by supercritical carbon dioxide. AB - The present study aimed to select the best medium for inactivation of Aspergillus fumigatus, Aspergillus spp. in section Nigri, A. niger, A. terreus var. terreus, A. tubingensis, Penicillium waksmanii, P. simplicissimum, and Aspergillus sp. strain no. 145 spores in clinical wastes by using supercritical carbon dioxide (SC-CO2). There were three types of solutions used including normal saline, seawater, distilled water, and physiological saline with 1% of methanol; each solution was tested at 5, 10, and 20 mL of the water contents. The experiments were conducted at the optimum operating parameters of supercritical carbon dioxide (30 MPa, 75 degrees C, 90 min). The results showed that the inactivation rate was more effective in distilled water with the presence of 1% methanol (6 log reductions). Meanwhile, the seawater decreases inactivation rate more than normal saline (4.5 vs. 5.1 log reduction). On the other hand, the experiments performed with different volumes of distilled water (5, 10, and 20 mL) indicated that A. niger spores were completely inactivated with 10 mL of distilled water. The inactivation rate of fungal spores decreased from 6 to 4.5 log as the amount of distilled water increased from 10 to 20 mL. The analysis for the spore morphology of A. fumigatus and Aspergillus spp. in section Nigri using scanning electron microscopy (SEM) has revealed the role of temperature and pressure in the SC-CO2 in the destruction of the cell walls of the spores. It can be concluded that the distilled water represent the best medium for inactivation of fungal spores in the clinical solid wastes by SC-CO2. PMID- 29785607 TI - Green certification, e-commerce, and low-carbon economy for international tourist hotels. AB - Increasing population and over-consumption are placing unprecedented demands on agriculture and natural resources. The Earth is suffering from global warning and environmental destruction while our agricultural systems are concurrently degrading land, water, biodiversity, and climate on a global scale. For a sustainable future, green certification, e-commerce, and environment education can boost low-carbon economy with decreasing carbon emissions, but very few researches address them for the hotel industry. This research studies the performance impact of e-commerce, international hotel chain, local hotel chain, and green certification for carbon emission reductions of international tourist hotels of Taiwan. It reveals that, after a sufficiently long time, there is an improvement in the environmental and economic performance of the green-certified hotel group. In addition, it reveals that, as recommended by the operation policy, the international hotel chain group together with e-commerce has better performance than local hotel chain. It is also discussed how to sustain the continuing improvement in low-carbon performance of the hotel industry. PMID- 29785608 TI - Reuse of organobentonites with a carbon dioxide responsive solvent. AB - Synthesized organobentonite (SOB), montmorillonite (MMT), and commercial organobentonite (COB) were used as adsorbents for paraffin oil, a model pollutant in land-based oil spills and oil pipeline rupture. The characterization of clays was carried out with scanning electron microscopy (SEM), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). After adsorption, oil was separated from adsorbents with a carbon dioxide responsive solvent N,N-dimethylcyclohexylamine (DMCHA), and DMCHA was subsequently separated from paraffin oil upon CO2 bubbling instead of distillation with high energy cost. The adsorption capacity of oil to SOB, MMT, and COB was 0.686, 1.124, and 1.239 g/g, respectively. It was found that the adsorption capacity and rinsed amount of the adsorbents depended on the d spacing, which is related to surfactant content. Electrical conductivity and pH measurements suggested that the separation process occurred via two steps. Firstly, during the initial 35 min, carbonate ions coexisted with bicarbonate ions. Then, only bicarbonate ions existed after the introduction of CO2 gas for 120 min. Thus, organobentonites were feasible for hydrocarbon adsorption and could be simply reused by an amine-based responsive solvent. This work provided a cost-effective and sustainable method of recycling of organobentonites and the responsive solvent, which can be used to deal with leaked oil and oil spills. PMID- 29785609 TI - Evaluation of FOCEI and SAEM Estimation Methods in Population Pharmacokinetic Analysis Using NONMEM(r) Across Rich, Medium, and Sparse Sampling Data. AB - BACKGROUND AND OBJECTIVES: First-order conditional estimation with interaction (FOCEI) is one of the most commonly used estimation methods in nonlinear mixed effects modeling, while the stochastic approximation expectation maximization (SAEM) is the newer estimation algorithm. This work aimed to compare the performance of FOCEI and SAEM methods when using NONMEM(r) with the classical one and two-compartment models across rich, medium, and sparse data. METHODS: One- and two-compartment models of the previous studies were used to simulate data in three scenarios: rich, medium, and sparse data. For each scenario, there were 100 data sets, containing 100 individuals in each data set. Every data set was estimated with both FOCEI and SAEM methods. The simulation and estimation were performed using NONMEM(r). The completion rates, percentage of relative estimation errors (%RERs), root mean square errors (RMSEs), and runtimes were considered to assess the completion, accuracy, precision, and speed of estimation, respectively. RESULTS: Both FOCEI and SAEM methods provided comparable completion rates, median %RERs (ranged from - 9.03 to 3.27% for FOCEI and - 9.17 to 3.27% for SAEM) and RMSEs (ranged from 0.0004 to 1.244 for FOCEI and 0.0004 to 1.131 for SAEM) for most parameters in both models across three scenarios. The run times were much shorter with FOCEI (ranged from 0.18 to 0.98 min) compared to SAEM method (ranged from 4.64 to 12.03 min). CONCLUSIONS: For the classical one- and two-compartment models, FOCEI method exhibited comparable performance similar to SAEM method but with significantly shorter runtimes across rich, medium, and sparse sampling scenarios. PMID- 29785611 TI - Correction to: Top-down, Bottom-up and Sideways: the Multilayered Complexities of Multi-level Actors Shaping Forest Governance and REDD+ Arrangements in Madre de Dios, Peru. AB - The article Top-down, bottom-up and sideways: the multilayered complexities of multi-level actors shaping forest governance and REDD+ arrangements in Madre de Dios, Peru, written by Dawn Rodriguez-Ward, Anne M. Larson, Harold Gordillo Ruesta, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 3 January 2018 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on (25 April 2018) to PMID- 29785610 TI - Evaluation of Strategies for the Assessment of Drug-Drug Interactions Involving Cytochrome P450 Enzymes. AB - BACKGROUND AND OBJECTIVES: Drug-drug interactions (DDIs) can occur when one drug alters the metabolism of another drug. Drug metabolism mediated by cytochrome P450 enzymes (CYPs) is responsible for the majority of metabolism of known drugs and inhibition of CYP enzymes is a well-known cause of DDIs. In the current study, the use of various human liver microsomes (HLM)-based methods to determine occurrence of CYP-mediated metabolism-dependent inhibition (MDI) and possible follow-up studies were evaluated. METHODS: Human CYP inhibition was studied using the following methodologies: direct inhibition and (non-diluted) IC50-shift assays, a ferricyanide-based reversibility assay, a spectrophotometric metabolic intermediate complex (MIC) assay, and recording of reduced carbon monoxide (CO) difference spectra. HLM incubations in the presence and absence of NADPH and glutathione (GSH) were performed to study the possible formation of CYP-dependent GSH adducts. HLM incubations with the radiolabeled inhibitors mifepristone and paroxetine were performed to study CYP-mediated covalent binding. RESULTS: Dihydralazine and furafylline displayed irreversible MDI of CYP1A2. Paroxetine displayed both quasi-irreversible and irreversible MDI of CYP2D6, formation of CYP-dependent GSH adducts was observed, while CYP-mediated covalent binding occurred which was decreased in the presence of GSH. Mifepristone displayed irreversible MDI of CYP3A4, formation of CYP-dependent GSH adducts was observed, while CYP-mediated covalent binding occurred which was decreased in the presence of GSH. Troleandomycin and verapamil displayed quasi-irreversible MDI of CYP3A4; MIC formation was observed, while no formation of CYP-dependent GSH adducts occurred. CONCLUSIONS: This study gives a representative overview of current methodologies that can be used to study CYP inhibition. The here presented strategy can be applied as a tool during risk evaluation of CYP-mediated DDIs. PMID- 29785612 TI - Water, Forests, People: The Swedish Experience in Building Resilient Landscapes. AB - A growing world population and rapid expansion of cities increase the pressure on basic resources such as water, food and energy. To safeguard the provision of these resources, restoration and sustainable management of landscapes is pivotal, including sustainable forest and water management. Sustainable forest management includes forest conservation, restoration, forestry and agroforestry practices. Interlinkages between forests and water are fundamental to moderate water budgets, stabilize runoff, reduce erosion and improve biodiversity and water quality. Sweden has gained substantial experience in sustainable forest management in the past century. Through significant restoration efforts, a largely depleted Swedish forest has transformed into a well-managed production forest within a century, leading to sustainable economic growth through the provision of forest products. More recently, ecosystem services are also included in management decisions. Such a transformation depends on broad stakeholder dialog, combined with an enabling institutional and policy environment. Based on seminars and workshops with a wide range of key stakeholders managing Sweden's forests and waters, this article draws lessons from the history of forest management in Sweden. These lessons are particularly relevant for countries in the Global South that currently experience similar challenges in forest and landscape management. The authors argue that an integrated landscape approach involving a broad array of sectors and stakeholders is needed to achieve sustainable forest and water management. Sustainable landscape management integrating water, agriculture and forests-is imperative to achieving resilient socio-economic systems and landscapes. PMID- 29785614 TI - Cascade of care and factors associated with virological suppression among HIV positive persons linked to care in the Test and Keep in Care (TAK) project. AB - INTRODUCTION: Early treatment remains the most effective HIV prevention strategy; poor linkage to care after HIV diagnosis may compromise this benefit. We sought to better understand patient characteristics and their association with virological suppression (VS) following cART initiation. METHODS: The TAK project collects pre-linkage to care and clinical data on patients diagnosed with HIV in voluntary testing facilities in central Poland. Data collected for persons diagnosed in 2010-2013 were linked with HIV clinic records. Individuals linked to care who commenced cART were followed from until the earliest of first VS (HIV RNA < 50 copies/ml), last visit, death or 6 January 2016. Cox-proportional hazard models were used to identify factors associated with first viral suppression. RESULTS: 232 persons were HIV positive, 144 (62%, 95% CI 55, 68%) linked to care, 116 (81% of those linked to care, 95% CI 73, 87%) started cART during follow up, of which 113 (97%, 95% CI 93, 99%) achieved VS. Non-PI based regimen (for integrase inhibitors aHR: 5.03: 1.90, 13.32) and HLA B5701-positive (aHR: 3.97: 1.33, 11.85) were associated with higher chance of VS. Unknown syphilis status (aHR: 0.27: 0.13, 0.57) and higher HIV RNA (aHR a tenfold increase: 0.56: 0.42, 0.75) remained associated with lower chance of VS. CONCLUSIONS: Although a low proportion of persons were linked to care, almost all those linked to care started cART and achieved rapid VS. The high rates of VS were irrespective of prior HIV-associated risk behaviours. Linkage to care remains the highest priority in prevention strategies in central Poland. PMID- 29785615 TI - Molecular characterization of proton beam-induced mutations in soybean using genotyping-by-sequencing. AB - Proton beam irradiation is a next-generation technique to develop mutant crop varieties. The mutagenic effects and molecular mechanisms of radiation are important multi-disciplinary research subjects. This study was conducted to investigate the types of mutations induced in the soybean genome by proton beam irradiation. In total, 22 plants, including 10 M2 plants treated with proton beam irradiation at 118 and 239 Gy, each, and two wild-type plants (Daepung) were sequenced by genotyping-by-sequencing (GBS). In total, 7453 single nucleotide polymorphisms (SNPs) were detected in the 20 M2 plants, compared with the two wild-type controls. The SNP frequency was 1/36,976 bp with proton beam irradiation at 118 Gy, and 1/32,945 bp at 239 Gy. Of these, 3569 SNPs were detected in genic regions. We observed that proton beam irradiation induced more substitutions than small insertion-deletions (INDELs). Based on the mutagenic effect of proton beam irradiation, the frequency of transition mutations was shown to be higher than that of transversions. The proton beam-induced SNPs were distributed uniformly in most of the chromosomes. Gene ontology (GO) analysis showed that there were many genes involved in protein metabolic process under biological process, intracellular membrane-bounded organelle under cellular component, and nucleic acid binding under molecular function. This study could provide valuable information for investigating the potential mechanisms of mutation, and guidance for developing soybeans cultivars using mutation breeding. PMID- 29785613 TI - Neuroinfections caused by fungi. AB - BACKGROUND: Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. METHODS: One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. RESULTS: The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. CONCLUSION: Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality. PMID- 29785616 TI - Tracking Toxoplasma gondii in freshwater ecosystems: interaction with the invasive American mink (Neovison vison) in Spain. AB - Water-borne transmission may play an important role in the epidemiology of Toxoplasma gondii. Mammals closely related to freshwater ecosystems, such as the American mink (Neovison vison), are potentially valuable sentinels for T. gondii. To assess the importance of freshwater ecosystems in T. gondii epidemiology, sera of 678 American minks collected during the 2010 to 2015 Spanish national eradication campaigns were tested for the presence of T. gondii antibodies using the modified agglutination test (MAT, cut-off 1:25). A high prevalence of samples, 78.8% (CI95%: 75.5-81.8), were seropositive. In addition, a specific real-time PCR was performed in 120 brain samples and the parasite DNA was detected in 9.2% (CI95%: 5.2-15.7). Significant differences in seroprevalence were detected among bioregions, with the highest levels detected in coastal areas, and by age. The higher seroprevalence observed in older animals (80.0% adults versus 68.7% juveniles) confirms the importance of the horizontal transmission. These results indicate a widespread presence of T. gondii oocysts in freshwater ecosystems from Spain and further support the importance of water borne transmission in the epidemiology of T. gondii. PMID- 29785617 TI - Heat shock, but not temperature, is a biological trigger for the exsheathment of third-stage larvae of Haemonchus contortus. AB - Gastrointestinal parasites are an important health issue in grazing ruminants. Understanding the processes involved in the transition from the free living to the parasitic life stage of these nematodes is one avenue to identifying new targets amenable to future intervention. The transition to parasitism is initiated by exsheathment and is triggered by the sudden change in environment after ingestion of the infective larva by the host. Two major changes in environment are the increases in temperature and carbon dioxide (CO2) levels. For CO2 a role in exsheathment has been described previously, but the exact role of temperature was unclear. The current study is the first to investigate the importance of temperature in triggering exsheathment of Haemonchus contortus. Carbon dioxide induced exsheathment in H. contortus proved to be temperature dependent, as no exsheathment was observed at room temperatures. However, the temperature requirement to trigger exsheathment was quite specific. A rapid change in temperature (heat shock) very efficiently induced high levels of exsheathment. In contrast, when the larvae were exposed to a slow increase in temperature, the exsheathment response was smaller and delayed. Further investigation revealed that timing of the heat shock in relation to the CO2 administration was crucial, as well as the final temperature and magnitude of the heat shock. In conclusion, these data indicate that heat shock rather than temperature itself is a crucial aspect in triggering the biological exsheathment cascade, and thus infection process, of H. contortus. PMID- 29785618 TI - A quick and simple benchtop vortex egg-disruption approach for the molecular diagnosis of Fasciola hepatica from ruminant faecal samples. AB - Commonly employed diagnostic methods for Fasciola spp., such as a traditional sedimentation and faecal egg count, or a commercially available coprological ELISA, have limitations in their sensitivity or ability to differentiate species. A reliable DNA isolation method coupled with real-time PCR addresses these issues by providing highly sensitive and quantitative molecular diagnosis from faecal samples. The current study evaluated a standard benchtop vortex for F. hepatica egg disruption in sheep and cattle faecal samples and determined the minimum faecal egg load required for a positive result from un-concentrated (raw) faecal samples. The minimum faecal egg load for a positive real-time PCR result from 150 mg raw faecal sample was 10 and 20 eggs per gram for sheep and cattle, respectively. No significant difference (P = 0.4467) between disruptions on a benchtop vortex for 5 or 10 min was observed when compared to 40 s of disruption at 6.0 m/s in a benchtop homogeniser. PMID- 29785619 TI - Comparative analyses of the mitochondrial genome of the sheep ked Melophagus ovinus (Diptera: Hippoboscidae) from different geographical origins in China. AB - The sheep ked Melophagus ovinus is mainly found in Europe, Northwestern Africa, and Asia. Although M. ovinus is an important ectoparasite of sheep in many countries, the population genetics, molecular biology, and systematics of this ectoparasite remain poorly understood. Herein, we determined the mitochondrial (mt) genome of M. ovinus from Gansu Province, China (MOG) and compared with that of M. ovinus Xinjiang Uygur Autonomous Region, China (MOX). The mt genome sequence (15,044 bp) of M. ovinus MOG was significantly shorter (529 bp) than M. ovinus MOX. Nucleotide sequence difference in the whole mt genome except for non coding region was 0.37% between M. ovinus MOG and MOX. For the 13 protein-coding genes, comparison revealed sequence divergences at both the nucleotide (0-1.1%) and amino acid (0-0.59%) levels between M. ovinus MOG and MOX, respectively. Interestingly, the cox1 gene of M. ovinus MOX is predicted to employ unusual mt start codons AAA, which has not been predicted previously for any parasite genome. Phylogenetic analyses showed that M. ovinus (Hippoboscoidea) is related to the superfamilies Oestroidea + Muscoidea. Our results have also indicated the paraphylies of the four families (Anthomyiidae, Calliphoridae, Muscidae, and Oestridae) and two superfamilies (Oestroidea and Muscoidea). This mt genome of M. ovinus provides useful molecular markers for studies into the population genetics, molecular biology, and systematics of this ectoparasite. PMID- 29785620 TI - How asymptomatic are early cancer patients of five organs based on registry data in Japan. AB - BACKGROUND: One reason for the low cancer screening rate in Japan is that people are not concerned about cancer if they do not have symptoms. METHODS: The authors retrospectively analyzed 18,405 cancer patients using hospital-based cancer registry data collected between 2007 and 2013 at the 13 hospitals of Shimane Prefecture, Japan. The symptomatic rates of five cancers (stomach, colorectal, lung, breast, and cervix) at each stage and the time of early diagnosis were investigated. The early detection rates of symptomatic and asymptomatic individuals were investigated. RESULTS: The percentages of symptomatic cases tended to increase with progressive stages. The odds ratio (OR) of stage IV compared with that of stage I was 12.23 for stomach, 7.21 for colorectal, 16.91 for lung, 10.30 for breast, and 51.62 for cervical cancer. The proportions of early symptomatic cases at the time of diagnosis were low. Compared with the percentage of early symptomatic cases of stomach cancer of 25.5%, the percentage of lung cancer was the lowest, at 8.2% (OR 0.26), and the percentage of breast cancer was the highest, at 30.2% (OR 1.26). The percentages of early symptomatic cases of colorectal and cervical cancer were 18.9% (OR 0.68) and 19.9% (OR 0.73), respectively. The early detection rates of the asymptomatic and symptomatic groups were 77.6 and 36.1%, respectively. CONCLUSION: Cancer registry data indicate that early cancers are asymptomatic, and once symptoms appear, treatment may not be effective. Policy makers should inform people of the necessity of cancer screening before they have symptoms. PMID- 29785621 TI - Comparison of efficacy and toxicity of second-line combination chemotherapy regimens in patients with advanced urothelial carcinoma. AB - BACKGROUND: The aim of this study was to evaluate the efficacy and toxicities of second-line chemotherapy regimens with docetaxel and gemcitabine (GD), or paclitaxel and gemcitabine (GP) for advanced or metastatic urothelial carcinoma (UC) that did not respond to first-line platinum-based chemotherapy. METHODS: From 2002 to 2017, 78 patients with metastatic UCs that progressed after platinum based chemotherapy were treated with either GD (n = 41) or GP (n = 37). We compared these two different regimens by analyzing their efficacy and toxicities in a retrospective manner. RESULTS: Of the 78 patients enrolled in this study, it was possible to determine treatment efficacy in 70; the proportion of patients with objective response and disease control were 8.6 (9/70) and 54.3% (38/70), respectively. The median progression-free survival and overall survival in the total population (GP and GD) were 3.5 (95% CI 0.6-53.3) and 9.6 months (95% CI 1.2-53.3), respectively. There was no significant difference between the two regimens (GD or GP) regarding survival outcomes. Treatment-related adverse events were mostly manageable, but one patient died as a result of febrile neutropenia. The presence of liver metastasis and anemia (Hb < 10.0 g/dl) was prognostic factors for worse survival. CONCLUSIONS: Combination chemotherapy with either GP or GD was a favorable and well-tolerated second-line treatment regimen for patients with advanced or metastatic UC following the failure of a platinum-based regimen. Further study using a large prospective cohort is needed to identify patients who will benefit from second-line combination therapy. PMID- 29785623 TI - Synthesis, Spectroscopic Characterization and Polymerization Abilities of Blue and Green Light Emitting Oxazol-5-one Fluorophores. AB - New fluorescent thiophenyl group containing oxazol-5-one fluorophores of 3a (4-(3 thiophenylmethylene)-2-phenyloxazol-5-one), 3b (4-(3-thiophenylmethylene)-2-(4 tolyl)oxazol-5-one) and 3c (4-(3-thiophenylmethylene)-2-(4-nitrophenyl)oxazol-5 one) were synthesized and characterized. The newly synthesized oxazol-5-ones absorption and fluorescence characteristics were studied in some solvents of varying polarities. The heterocyclic chromophores were fluorescent, with two of them, 3a and 3b, emitting blue light, whilst the other one, 3c, emitting green light. The emission maxima of the derivatives varied between 415 and 572 nm according as the extent of conjugation and solvent polarity. As solvent polarity increased, 3c derivatives emission spectra displayed a large bathochromic shift, which revealed the considerable change of the dipole moment of the fluorescent structure because of an intramolecular charge transfer interaction. Furthermore, oxazolones polymerization ability via the thiophenyl group linked to the oxazol-5 one heterocycle showed that copolymerization of 3a was achieved, but homopolymerization was not observed. PMID- 29785624 TI - Longitudinal Neuroimaging Hippocampal Markers for Diagnosing Alzheimer's Disease. AB - Hippocampal atrophy measures from magnetic resonance imaging (MRI) are powerful tools for monitoring Alzheimer's disease (AD) progression. In this paper, we introduce a longitudinal image analysis framework based on robust registration and simultaneous hippocampal segmentation and longitudinal marker classification of brain MRI of an arbitrary number of time points. The framework comprises two innovative parts: a longitudinal segmentation and a longitudinal classification step. The results show that both steps of the longitudinal pipeline improved the reliability and the accuracy of the discrimination between clinical groups. We introduce a novel approach to the joint segmentation of the hippocampus across multiple time points; this approach is based on graph cuts of longitudinal MRI scans with constraints on hippocampal atrophy and supported by atlases. Furthermore, we use linear mixed effect (LME) modeling for differential diagnosis between clinical groups. The classifiers are trained from the average residue between the longitudinal marker of the subjects and the LME model. In our experiments, we analyzed MRI-derived longitudinal hippocampal markers from two publicly available datasets (Alzheimer's Disease Neuroimaging Initiative, ADNI and Minimal Interval Resonance Imaging in Alzheimer's Disease, MIRIAD). In test/retest reliability experiments, the proposed method yielded lower volume errors and significantly higher dice overlaps than the cross-sectional approach (volume errors: 1.55% vs 0.8%; dice overlaps: 0.945 vs 0.975). To diagnose AD, the discrimination ability of our proposal gave an area under the receiver operating characteristic (ROC) curve (AUC) [Formula: see text] 0.947 for the control vs AD, AUC [Formula: see text] 0.720 for mild cognitive impairment (MCI) vs AD, and AUC [Formula: see text] 0.805 for the control vs MCI. PMID- 29785622 TI - Retrospective surveillance of antibiotic use in maternity wards and neonatal intensive care units in Saint Petersburg, Russia. AB - Antibiotic overuse in infants is associated with an increased risk of serious adverse events. Development of antibiotic stewardship programs aimed at reducing overall antibiotic consumption requires epidemiological surveillance. Retrospective surveillance and evaluation of all antibiotics provided to every infant admitted to maternal wards or neonatal intensive care units (NICUs) from 01 January 2014 to 31 December 2014 were performed in five medical centers of Saint Petersburg, Russia. Types of antibiotics and dates of administration were recorded. Antibiotic use was quantified by length of therapy (length of therapy, LOT, per 1000 patient-days, PD) and days of therapy (DOT/1000 PD). An additional parameter named "instant DOT/1000 PD" was introduced by authors for assessment of longitudinal patterns of administrations. Antibiotic load was 825.6 DOT/1000 PD in maternity wards and 1425.8 DOT/1000 PD in the NICUs. These levels are two to four times higher than DOTs reported in the USA for a level III NICU (348 DOT/1000PD). Antibiotic load was associated with the length of hospital stay (LOS) and birth weight. These associations were distorted when assessed using the conventional parameters, LOT and DOT, because they do not reflect the longitudinal component of treatment and underestimate antibiotic load when a patient stays in hospital without treatment. The proposed additional parameter successfully overcame these flaws and uncovered hidden associations. Severe overuse of antibiotics may be taking place in Russia and antibiotic stewardship development should be urged. Instant DOT/1000 PD is a more powerful tool in assessing treatment patterns than DOT/1000 PD. PMID- 29785625 TI - Exploring the Association Between Electronic Health Record Use and Burnout Among Psychiatry Residents and Faculty: a Pilot Survey Study. AB - OBJECTIVE: Burnout is a phenomenon with profound negative effects on the US healthcare system. Little is known about the relationship between time spent working on electronic health record (EHR) and burnout among psychiatry residents. The purpose of this study is to generate preliminary data on EHR use and burnout among psychiatry residents and faculty. METHODS: In August 2017, psychiatry residents and faculty at an academic medical center were given the Maslach Burnout Inventory (MBI), a standardized measurement tool for burnout, and a survey of factors related to EHR use and potential risk factors for burnout. MBI data along with selected burnout risk and protective factors were analyzed with R Studio software. RESULTS: Responses were obtained from 40 psychiatry residents (73%) and 12 clinical faculty members (40%). Residents reported 22 h per week using EHR on average. Mean score of residents surveyed in postgraduate year (PGY) 1-4 met criteria for high emotional exhaustion associated with burnout. The magnitude of correlation between EHR use and emotional exhaustion was stronger than for other burnout factors including sleep, exercise, and clinical service. CONCLUSIONS: Psychiatry residents show signs of high emotional exhaustion, which is associated with burnout. Results demonstrate a strong positive correlation between EHR use and resident burnout. Time spent on EHR use may be an area of importance for psychiatry program directors and other psychiatric educators to consider when seeking to minimize burnout and promote wellness. PMID- 29785626 TI - Sex Attractant Pheromones of Virgin Queens of Sympatric Slave-Making Ant Species in the Genus Polyergus, and their Possible Roles in Reproductive Isolation. AB - Species of the ant genus Polyergus are social parasites that steal brood from colonies of their hosts in the closely related genus Formica. Upon emergence as adults in a mixed population, host Formica workers carry out all the normal worker functions within the Polyergus colony, including foraging, feeding, grooming, and rearing brood of the parasitic Polyergus ants. Some unmated Polyergus gynes (queens) run in the raiding columns of their colonies and attract males by releasing a pheromone from their mandibular glands. There are two Polyergus species groups in North America: an eastern P. lucidus group and a western P. breviceps group. One species of each of these groups, P. lucidus Mayr and P. mexicanus Emery, are sympatric in Missouri. In this study, we characterized the sex pheromones of virgin queens of two species of the P. lucidus group (P. lucidus sensu stricto and P. sanwaldi) and one species of the P. breviceps group (P. mexicanus), and compared these with the previously identified sex pheromone of P. topoffi of the P. breviceps group. We then used sex pheromone blends reconstructed from synthesized components of the two groups to test their efficacy at reproductively isolating these species. We found that methyl 6-methylsalicylate is conserved as the major component of the pheromone blends for both Polyergus species groups; however, methyl (R)-3-ethyl-4 methylpentanoate is the species-specific minor component produced by P. lucidus group queens, and (R)-3-ethyl-4-methylpentan-1-ol is the crucial minor component for P. breviceps group queens. The optimal ratio of the major and minor components for P. lucidus group queens was about 100:1 salicylate to ester. In concurrent field trials in Missouri, males of P. lucidus sensu stricto and P. mexicanus (a member of the P. breviceps group) were attracted almost exclusively to their particular blends of sex pheromone components. To our knowledge, this is the first example of a possible sex-pheromone-based reproductive isolating mechanism in ants. PMID- 29785627 TI - Chemical Communication and Reproduction Partitioning in Social Wasps. AB - Social wasps encompass species displaying diverse social organization regarding colony cycle, nest foundation, caste differences (from none to significant dimorphism) and number of reproductive queens. Current phylogenetic data suggests that sociality occured independently in the subfamily Stenogastrinae and in the Polistinae+Vespinae clade. In most species, including those with the simplest social organization, colony reproduction is monopolised by a single or few females. Since their nest mates can also develop ovaries and lay eggs, dominant females must somehow inhibit them from reproducing. Physical interactions in the form of open aggression or, usually, ritualised dominance by the fertile females contribute to fertility inhibition in several species, but it is unlikely to function in large colonies. In the latter case, reproduction within the colony is likely to be regulated through pheromones. Relatively little is known about these semiochemicals. Studies on all the three social wasp subfamilies, revealed that cuticular hydrocarbon components differ in abundance between egg-laying and not egg-laying females and that their composition depends on fertility status. In several species, females have been reported to manifestly react towards females with activated ovaries, but there is little evidence to support the hypothesis that fertile individuals are either recognized through their CHC composition, or that over-represented CHC constituents can inhibit fertility. Moreover, very little information exists on the possibility that exocrine glands release fertility signals or chemicals inhibiting fertility. PMID- 29785628 TI - Gut-Associated Bacteria of Helicoverpa zea Indirectly Trigger Plant Defenses in Maize. AB - Insect-associated microbes can contribute to the physiological and ecological functions of insects. Despite a few examples in beetles and piercing-sucking insects, the varied mechanisms of how insect-associated bacteria mediate plant insect interactions are still not fully understood. The polyphagous herbivore Helicoverpa zea is a major agricultural pest that harbors certain microbes in their digestive systems. Enterobacter ludwigii is one of the gut-associated bacteria identified from field-collected caterpillars, and it has been shown to indirectly induce defenses in the dicot plant tomato by triggering the biosynthesis of salivary elicitors, but there are no clear mechanisms to show how gut microbes alter these salivary cues and how a different host plant responds to these inducible elicitors. Here, we conducted a series of assays to determine whether infection with E. ludwigii affects H. zea larval growth, immunity, and salivary responses and thus influences induced defenses of maize to herbivory. Inoculating lab-reared caterpillars with E. ludwigii, did not significantly affect the growth of caterpillars, but two immunity-related genes glucose oxidase (GOX) and lysozyme (LYZ) were more highly expressed in both salivary glands and midguts compared with MgCl2 solution-treated caterpillars. Oral elicitors were evaluated for their role in triggering maize-specific defense responses. Our results show that saliva and its main component protein glucose oxidase (GOX) from E. ludwigii-inoculated caterpillars played a role in inducing maize anti herbivore responses. These findings provide a novel concept that introducing bacteria to an herbivore may be an important approach to pest control through alteration of insect immune responses and thus indirect induction of plant resistance. PMID- 29785630 TI - Calcium Channels, Rho-Kinase, Protein Kinase-C, and Phospholipase-C Pathways Mediate Mercury Chloride-Induced Myometrial Contractions in Rats. AB - Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2)-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM-100 MUM) uterotonic effect which was significantly (p < 0.05) reduced in Ca2+ free solution and inhibited in the presence of nifedipine (1 MUM), a L-type Ca2+ channel blocker, thus suggesting the importance of extracellular Ca2+ and its entry through L-type calcium channels in HgCl2-induced myometrial contractions in rats. Cumulative concentration-response curve of HgCl2 was significantly (p < 0.05) shifted towards right in the presence of Y-27632 (10 MUM), a Rho-kinase inhibitor, suggesting the involvement of Ca2+-sensitization pathway in mediating HgCl2-induced myometrial contraction. HgCl2-induced myometrial contraction was also significantly (p < 0.05) inhibited in the presence of methoctramine or para fluoro-hexahydro-siladifenidol, a selective M2 and M3 receptor antagonists, respectively, which evidently suggest that mercury also interacts with M2 and M3 muscarinic receptors to produce myometrial contractions. U-73122 and GF-109203X, the respective inhibitors of PLC and PKC-dependent pathways, downstream to the receptor activation, also significantly (p < 0.05) attenuated the uterotonic effect of HgCl2 on rat uterus. Taken together, present study evidently reveals that HgCl2 interacts with muscarinic receptors and activates calcium signaling cascades involving calcium channels, Rho-kinase, protein kinase-C, and phospholipase-C pathways to exert uterotonic effect in rats. Graphical Abstract Graphical abstract depicting the mechanism of mercury-induced myometrial contraction in rats. M receptor: Muscarinic receptor; PIP2: phospho-inositol bisphosphate; PLC: phospholipase-C; DAG: diacyl glycerol; IP3: inositol triphosphate; IP3R: inositol triphosphate receptor; PKC; protein kinase-C; MLCP: myosin light chain phosphatise; MYPT: myosin phosphatase; SR: sarco-endoplasmic reticulum. PMID- 29785631 TI - Eating disorders risk among medical students: a global systematic review and meta analysis. AB - PURPOSE: Medical students appear to be a high-risk group to develop psychological problems including eating disorders (ED). The prevalence estimates of ED risk vary greatly between studies. This systematic review and meta-analysis was done to estimate the prevalence of ED risk among medical students. METHODS: An electronic search of EMBASE, MEDLINE, ProQuest and Google Scholar was conducted. Studies that reported the prevalence of ED risk among medical students and were published in English peer-reviewed journals between 1982 and 2017 were included. Information about study characteristics and the prevalence of ED risk were extracted by four investigators. Each article was reviewed independently by at least two investigators. Estimates were pooled using random-effects meta-analysis using the DerSimonian-Laird method. The main outcome of interest was the prevalence of ED risk in medical students. RESULTS: The prevalence of ED risk among medical students was extracted from nineteen cross-sectional studies across nine countries (total participants n = 5722). The overall pooled prevalence rate of ED risk was 10.4% (497/5722 students, 95% CI 7.8-13.0%), with statistically significant evidence between-study heterogeneity (Q = 295, tau2 = 0.003, I2 = 94.0%, P < 0.001). Prevalence estimates between studies ranged from 2.2 to 29.1%. CONCLUSION: In this systematic review and meta-analysis, the summary prevalence of ED risk among medical students was 10.4%. Further research is needed to identify and prevent ED in this population. Studies are also needed to investigate concurrent pathologies associated with ED risk. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis. PMID- 29785632 TI - Virulence Factors in Salmonella Typhimurium: The Sagacity of a Bacterium. AB - Currently, Salmonella enterica Typhimurium (ST) is responsible for most cases of food poisoning in several countries. It is characterized as a non-specific zoonotic bacterium that can infect both humans and animals and although most of the infections caused by this microorganism cause only a self-limiting gastroenteritis, some ST strains have been shown to be invasive, crossing the intestinal wall and reaching the systemic circulation. This unusual pathogenicity ability is closely related to ST virulence factors. This review aims to portray the main virulence factors in Salmonella Typhimurium, in order to better understand the strategies that this pathogen uses to reach the systemic circulation and increase its infectivity in humans and animals. Thus, the most studied Salmonella pathogenicity islands in Salmonella Typhimurium were detailed as to the functions of their encoded virulence factors. In addition, available knowledge on virulence plasmid was also compiled, as well as the chromosome regions involved in the virulence of this bacterium. PMID- 29785629 TI - Reproductive Dominance Strategies in Insect Social Parasites. AB - In eusocial insects, the high cost of altruistic cooperation between colony members has favoured the evolution of cheaters that exploit social services of other species. In the most extreme forms of insect social parasitism, which has evolved multiple times across most social lineages, obligately parasitic species invade the nests of social species and manipulate the workforce of their hosts to rear their own reproductive offspring. As alien species that have lost their own sociality, these social parasites still face social challenges to infiltrate and control their hosts, thus providing independent replicates for understanding the mechanisms essential to social dominance. This review compares socially parasitic insect lineages to find general trends and build a hypothetical framework for the means by which social parasites achieve reproductive dominance. It highlights how host social organization and social parasite life history traits may impact the way they achieve reproductive supremacy, including the potential role of chemical cues. The review discusses the coevolutionary dynamics between host and parasite during this process. Altogether, this review emphasizes the value of social parasites for understanding social evolution and the need for future research in this area. PMID- 29785636 TI - A letter to the editor referencing "Objective and subjective financial burden and its associations with health-related quality of life among lung cancer patients". PMID- 29785633 TI - Regulation of Thermostable Direct Hemolysin and Biofilm Formation of Vibrio parahaemolyticus by Quorum-Sensing Genes luxM and luxS. AB - Vibrio parahaemolyticus is a seafood opportunistic pathogen. There are evidences suggesting that virulence skills, including hemolytic activity and biofilm formation, are regulated by the luxM/luxS-dependent quorum-sensing system in V. parahaemolyticus, and their regulatory mechanism is not well understood. To better understand the virulence regulatory mechanism of V. parahaemolyticus, the luxM deletion (?luxM) and luxS deletion (?luxS) mutants were constructed and their impacts on growth, hemolysin activity, and biofilm were investigated. Results show that both luxM and luxS are involved in the adaptation to environmental conditions in early adaptive-log phase growth of V. parahaemolyticus. Thermostable direct hemolysin gene (tdh) was negatively regulated by luxM and positively regulated by luxS. The biofilm formation was negatively regulated by both luxS and luxM. This study provides an insight into some aspects of V. parahaemolyticus virulence regulation by luxM/luxS-dependent quorum-sensing system. PMID- 29785634 TI - A Cluster of Five Genes Essential for the Utilization of Dihydroxamate Xenosiderophores in Synechocystis sp. PCC 6803. AB - The unicellular freshwater cyanobacterium Synechocystis sp. PCC 6803 is capable of using dihydroxamate xenosiderophores, either ferric schizokinen (FeSK) or a siderophore of the filamentous cyanobacterium Anabaena variabilis ATCC 29413 (SAV), as the sole source of iron in the TonB-dependent manner. The fecCDEB1-schT gene cluster encoding a siderophore transport system that is involved in the utilization of FeSK and SAV in Synechocystis sp. PCC 6803 was identified. The gene schT encodes TonB-dependent outer membrane transporter, whereas the remaining four genes encode the ABC-type transporter FecB1CDE formed by the periplasmic binding protein FecB1, the transmembrane permease proteins FecC and FecD, and the ATPase FecE. Inactivation of any of these genes resulted in the inability of cells to utilize FeSK and SAV. Our data strongly suggest that Synechocystis sp. PCC 6803 can readily internalize Fe-siderophores via the classic TonB-dependent transport system. PMID- 29785637 TI - FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China. AB - Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake. PMID- 29785635 TI - Self-monitoring physical activity with a smartphone application in cancer patients: a randomized feasibility study (SMART-trial). AB - PURPOSE: Evidence accumulates that an active lifestyle positively influences cancer treatment outcome. A "smartphone application" (app) such as "RunKeeper," to self-monitor physical activity (PA) might be helpful. This study aimed to examine whether using RunKeeper to increase self-reported PA is feasible in cancer patients and to evaluate patients' opinion about using RunKeeper in a 12 week program. METHODS: Adult patients (n = 32), diagnosed with cancer, were randomized between usual care (n = 16) or a 12-week intervention with instructions to self-monitor PA with RunKeeper (n = 16). Changes in PA were determined with the Physical Activity Scale for the Elderly (PASE) at baseline (T0), 6 weeks (T1), and 12 weeks (T2). Usability and patients' experiences were tested at T2 with the System Usability Scale (SUS) and a semi-structured interview. RESULTS: Patient mean age was 33.6 years. Between T0 and T1, an increase in PA of 51% (medium estimated effect size r = 0.40) was found in PASE sum score in the intervention group compared with usual care. In addition, total minutes of PA increased with 46% (r = 0.37). These effects decreased over time (T2). Sedentary time decreased with 19% between T0 and T1 and 27% between T0 and T2. Usability was rated "good" and most patients found RunKeeper use helpful to improve PA. CONCLUSIONS: Self-monitoring PA with RunKeeper was safe and feasible in cancer patients. The RunKeeper use resulted in an increase in PA after 6 weeks. RunKeeper usability was rated good and can be used to study PA in cancer patients. TRIAL REGISTRATION: NCT02391454. PMID- 29785638 TI - Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity. AB - Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 ug/day) resulted in multifocal cerebellar Purkinje cell loss in a 6 month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions. Here we present the results of a 9-month toxicity study in which rhesus monkeys received intermittent intraputamenal infusions via convection-enhanced delivery. Animals were treated with GDNF (87.1 ug; N = 14) or vehicle (N = 6) once every 4 weeks for a total of 40 weeks (11 treatments). Four of the GDNF-treated animals were utilized in a satellite study assessing the impact of concomitant catheter repositioning prior to treatment. In the main study, eight animals (5 GDNF, 3 control) were euthanized at the end of the treatment period, along with the four satellite study animals, while the remaining eight animals (5 GDNF, 3 control) were euthanized at the end of a 12-week recovery period. There were no GDNF related adverse effects and in particular, no GDNF-related microscopic findings in the brain, spinal cord, dorsal root ganglia, or trigeminal ganglia. Therefore, 87.1 ug/4 weeks is considered the no observed adverse effect level for GDNF in rhesus monkeys receiving intermittent, convection-enhanced delivery of GDNF for 9 months. PMID- 29785639 TI - Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population. AB - PURPOSE: Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. STUDY DESIGN: Evaluation of diagnostic technology, Prospective, Clinical and experimental study. METHODS: A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. RESULTS: NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). CONCLUSIONS: The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test. PMID- 29785640 TI - Switching from high-fat diet to foods containing resveratrol as a calorie restriction mimetic changes the architecture of arcuate nucleus to produce more newborn anorexigenic neurons. AB - PURPOSE: These days, obesity threatens the health for which one of the main interventions is calorie restriction (CR). Due to the difficulty of compliance with this treatment, CR mimetics such as resveratrol (RSV) have been considered. The present study compared the effects of RSV and CR on hypothalamic remodeling in a diet-switching experiment. METHODS: C57BL/6 male mice received high-fat diet (HFD) for 4 weeks, subsequently their diet switched to chow diet, HFD + RSV, chow diet + RSV or CR diet for a further 6 weeks. Body weight, fat accumulation, hypothalamic apoptosis and expression of trophic factors as well as generation and fate specification of newborn cells in arcuate nucleus (ARC) were evaluated. RESULTS: Switching diet to RSV-containing foods leading to weight and fat loss after 6 weeks. In addition, not only a significant reduction in apoptosis but also a considerable increase in production of newborn cells in ARC occurred following consumption of RSV-enriched diets. These were in line with augmentation of hypothalamic ciliary neurotrophic factor and leukemia inhibitory factor expression. Interestingly, RSV-containing diets changed the fate of newborn neurons toward generation of more proopiomelanocortin than neuropeptide Y neurons. The CR had effects similar to those of RSV-containing diets in the all evaluated aspects besides neurogenesis in ARC. CONCLUSIONS: Although both RSV containing and CR diets changed the fate of newborn neurons to create an anorexigenic architecture for ARC, newborn neurons were more available after switching to RSV-enriched diets. It can be consider as a promising mechanism for future investigations. PMID- 29785641 TI - In Silico Analysis of Natural Resistance-Associated Macrophage Protein (NRAMP) Family of Transporters in Rice. AB - In Oryza sativa (rice) there are seven members in the NRAMP (natural resistance- associated macrophage protein) family of transporter proteins. They have been identified as OsNRAMP1, OsNRAMP2, OsNRAMP3, OsNRAMP4, OsNRAMP5, OsNRAMP6 and OsNRAMP7. Several metal ions like Zn2+, Mn2+, Fe2+, Cd2+ etc. have been studied to be transported via NRAMP transporter proteins in rice plant. In spite of this, very little information is available regarding these transporters. Hence it is important to computationally predict and characterize the OsNRAMP family of transporters for studying and understanding their molecular insights in future studies. For this purpose, various in silico methods and tools were used for the characterization of OsNRAMP family of transporter proteins. Physico-chemical properties of the protein sequences were calculated, putative transmembrane domains (TMDs) and conserved motif signatures were determined and their interaction partners were predicted. 3D models of all the members of OsNRAMP transporters were generated using online structure prediction tool followed by their analysis. In silico microarray analysis was done to understand the expression pattern of these transporters in rice plant. Currently, only limited knowledge is available about the structural and functional aspects of these transporters, hence this study would provide more theoretical information about them. PMID- 29785642 TI - Differential Binding of Active and Inactive Integrin to Talin. AB - Bi-directional signaling of integrins plays an important role in platelet and leukocyte function. Talin plays a key role in integrin bi-directional signaling and its binding to integrin is highly regulated. The precise regulation of the recruitment and binding of talin to integrin is still being elucidated. In particular, the recruitment of talin to integrin is controlled by the RAP-1 and RIAM/lamellipodin signaling axis and the affinity between talin and integrin is regulated by the conformation or protease cleavage of talin. However, whether the binding between integrin and talin is also regulated by integrin conformation has not been thoroughly explored before. In this work, we used biochemical binding assays to study the potential role of integrin conformational changes in integrin talin interactions. Constitutively active integrin alphaIIbb3 binds markedly stronger to talin than inactive alphaIIbb3. Inactive alphaIIbb3 markedly increases its binding to talin once activated, regardless of how alphaIIbb3 is activated. Further, the increased binding to talin is b3 tail dependent. Our results suggest that integrin conformation is another regulatory mechanism for integrin-talin interaction. PMID- 29785644 TI - Child with Isolated Motor Delay: Look at the Neuroimage. PMID- 29785643 TI - Estimating and mapping forest biomass using regression models and Spot-6 images (case study: Hyrcanian forests of north of Iran). AB - Hyrcanian forests of North of Iran are of great importance in terms of various economic and environmental aspects. In this study, Spot-6 satellite images and regression models were applied to estimate above-ground biomass in these forests. This research was carried out in six compartments in three climatic (semi-arid to humid) types and two altitude classes. In the first step, ground sampling methods at the compartment level were used to estimate aboveground biomass (Mg/ha). Then, by reviewing the results of other studies, the most appropriate vegetation indices were selected. In this study, three indices of NDVI, RVI, and TVI were calculated. We investigated the relationship between the vegetation indices and aboveground biomass measured at sample-plot level. Based on the results, the relationship between aboveground biomass values and vegetation indices was a linear regression with the highest level of significance for NDVI in all compartments. Since at the compartment level the correlation coefficient between NDVI and aboveground biomass was the highest, NDVI was used for mapping aboveground biomass. According to the results of this study, biomass values were highly different in various climatic and altitudinal classes with the highest biomass value observed in humid climate and high-altitude class. PMID- 29785645 TI - Concurrent coupling of realistic and ideal models of liquids and solids in Hamiltonian adaptive resolution simulations. AB - To understand the properties of a complex system it is often illuminating to perform a comparison with a simpler, even idealised one. A prototypical application of this approach is the calculation of free energies and chemical potentials in liquids, which can be decomposed in the sum of ideal and excess contributions. In the same spirit, in computer simulations it is possible to extract useful information on a given system making use of setups where two models, an accurate one and a simpler one, are concurrently employed and directly coupled. Here, we tackle the issue of coupling atomistic or, more in general, interacting models of a system with the corresponding idealised representations: for a liquid, this is the ideal gas, i.e. a collection of non-interacting particles; for a solid, we employ the ideal Einstein crystal, a construct in which particles are decoupled from one another and restrained by a harmonic, exactly integrable potential. We describe in detail the practical and technical aspects of these simulations, and suggest that the concurrent usage and coupling of realistic and ideal models represents a promising strategy to investigate liquids and solids in silico. PMID- 29785646 TI - Investigating the Spatial Trends in the Level of Organic Contaminants in the Ethiopian Rift Valley Lakes Using Semipermeable Membrane Devices. AB - Organic pollutants in the Ethiopian Rift Valley Lakes are the major factors that contribute to severe environmental problem. SPMDs were deployed for the analysis of selected organic pollutants for 1 month at 2 sites in Lakes Hawassa, Ziway and Koka, Ethiopia. From SPMDs placed in the three lakes, the predominant OCPs were DDT which comprise 67% and followed by endosulfan 23% of the total organochlorine pesticides (OCPs) retrieved. The highest level of OCPs, in general, was found in the SPMDs deployed in Lake Ziway with the mean concentration of 308.5 ng/SPMD. However, the concentrations of polychlorinated biphenyls (PCBs) were the highest in the SPMDs deployed in Lake Hawassa with mean concentration of 50.2 ng/SPMD. Spatial variation on the accumulation of OCPs and PCBs among the lakes depends on the shoreline activities, distance of the lakes from point and non-point sources, and the biofouling factors. PMID- 29785647 TI - mRNA Analysis of Genes Encoded with Phytochelatin Synthase (PCS) in Rice Seedlings Exposed to Chromium: The Role of Phytochelatins in Cr Detoxification. AB - Transcriptional changes of genes encoded with phytochelatins synthase (PCS) was investigated in rice seedlings exposed to potassium chromate Cr(VI) or chromium nitrate Cr(III) using qRT-PCR. Our study demonstrates that both Cr variants initiated different responses of phytochelatin content and PCS activities in rice tissues. Six putative PCS genes were expressed differentially in response to both Cr species. Comparing gene expression between root/shoots, only LOC_Os05g34290.1 and LOC_Os06g01260.1 genes were expressed in similar patterns in Cr(VI) treatment, while none of them were expressed equally in Cr(III) treatments. Inconsistent expression of PCS genes in two Cr variants as well as in rice tissues were most likely related to its individual chemical properties and chemical speciation. Results presented here indicate that the role of phytochelatins in Cr detoxification between two Cr variants in rice was different and six putative PCS genes functioned differently in stimulating PCS activities and regulating phytochelatin formation. PMID- 29785648 TI - Ultrafiltration for the Determination of Cu Complexed with Dissolved Organic Matters of Different Molecular Weight from a Eutrophic River, China. AB - The molecular weight of dissolved organic matter (DOM) is one of the essential factors controlling the properties of metal complexes. A continuous ultrafiltration experiment was designed to study the properties of Cu complexes with different molecular weights in a river before and after eutrophication. The results showed that the concentration of DOM increased from 26.47 to 38.20 mg/L during the eutrophication process, however, DOM was still dominated by the small molecular weight fraction before and after eutrophication. The amount of Cu-DOM complexes increased with the increasing of molecular weight, however, the amounts of DOM-Cu complexes before eutrophication were higher than those after eutrophication. This is because DOM contained more -COOH and -OH before eutrophication and these functional groups are the active sites complexed with Cu. PMID- 29785649 TI - Intersections of discrimination due to unemployment and mental health problems: the role of double stigma for job- and help-seeking behaviors. AB - PURPOSE: The everyday lives of unemployed people with mental health problems can be affected by multiple discrimination, but studies about double stigma-an overlap of identities and experiences of discrimination-in this group are lacking. We therefore studied multiple discrimination among unemployed people with mental health problems and its consequences for job- and help-seeking behaviors. METHODS: Everyday discrimination and attributions of discrimination to unemployment and/or to mental health problems were examined among 301 unemployed individuals with mental health problems. Job search self-efficacy, barriers to care, and perceived need for treatment were compared among four subgroups, depending on attributions of experienced discrimination to unemployment and to mental health problems (group i); neither to unemployment nor to mental health problems (group ii); mainly to unemployment (group iii); or mainly to mental health problems (group iv). RESULTS: In multiple regressions among all participants, higher levels of discrimination predicted reduced job search self efficacy and higher barriers to care; and attributions of discrimination to unemployment were associated with increased barriers to care. In ANOVAs for subgroup comparisons, group i participants, who attributed discrimination to both unemployment and mental health problems, reported lower job search self-efficacy, more perceived stigma-related barriers to care and more need for treatment than group iii participants, as well as more stigma-related barriers to care than group iv. CONCLUSIONS: Multiple discrimination may affect job search and help seeking among unemployed individuals with mental health problems. Interventions to reduce public stigma and to improve coping with multiple discrimination for this group should be developed. PMID- 29785650 TI - A Probiotic for Ulcerative Colitis: The Culture Wars Continue. PMID- 29785651 TI - Genetic analysis of the human insulin-like 3 gene in pediatric patients with testicular torsion. AB - PURPOSE: Testicular torsion (TT) mainly affects boys under 18 years old. To avoid orchiectomy, TT requires an immediate operative management. The etiology of TT is still controversial. Observed familiar recurrence suggests the presence of a genetic involvement. The INSL3 gene consists of two exons, and it is specifically expressed in fetal and adult Leydig cells. In transgenic mice, deletion of this gene was observed an increased testicular mobility and testicular torsion. We have hypothesized the possible involvement of the INSL3 gene as a predisposing factor of human TT. METHODS: We performed genetic analysis in 25 pediatric patients with unilateral and intravaginal TT (left, n = 13, 56%; right, n = 12, 48%). The age of the patients ranged from 1 to 16 years (median age n = 10.4 +/- 5.46 years). In this study, we included two first male cousins affected by TT. Venous peripheral blood samples was obtained after parental written informed consent. RESULTS: The Thr60Ala polymorphism was detected in exon 1 of INSL3 gene and other 2 rarer variants (rs1047233 and rs1003887) were identified in the 3' untranslated region. These variants are prevalent in patients with TT instead of healthy subjects. CONCLUSIONS: Additional studies in a larger population are needed to better understand the clinical consequence of the INSL 3 variations founded. This would allow in the future to identify the patients at risk of TT to improve clinical management. PMID- 29785653 TI - Valproic acid treatment response in vitro is determined by TP53 status in medulloblastoma. AB - PURPOSE: Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. METHODS: Dose-response curve determined IC50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments. Quantitative PCR evaluated gene expression levels of AKT, CTNNB1, GLI1, KDM6A, KDM6B, NOTCH2, PTCH1, and TERT, before and after treatment. Besides, we performed next-generation sequencing (NGS) for PTCH1, TERT, and TP53 genes. RESULTS: The most effective treatment to reduce viability was combined for D283MED and ONS-76; and CDDP single for DAOY cells (p < 0.0001). TERT, GLI1, and AKT genes were overexpressed after treatments with VA. D283MED and ONS-76 cells presented variants in TERT and PTCH1, respectively and DAOY cell line presented a TP53 mutation. CONCLUSIONS: MB tumors belonging to SHH molecular subgroup, with TP53MUT, would be the ones that present high risk in relation to VA use during the treatment, while TP53WT MBs can benefit from VA therapy, both SHH and groups 3 and 4. Our study shows a new perspective about VA action in medulloblastoma cells, raising the possibility that VA may act in different patterns. According to the genetic background of MB cell, VA can stimulate cell cycle arrest and apoptosis or induce resistance to treatment via signaling pathways activation. PMID- 29785655 TI - Early results after operatively versus non-operatively treated flail chest: a retrospective study focusing on outcome and complications. AB - PURPOSE: Flail chest was traditionally treated non-operatively using mechanical ventilation and pain control. In order to reduce the occurrence of ventilation associated complications and long-term disability, operative rib fixation is becoming a proven standard therapy for these patients. However, the consequences of the surgical complications may influence success rates negatively. The aim of this study was to compare the outcome of flail chest treatment by surgical rib fixation with non-operative treatment, with special focus on the impact of surgical complications. METHODS: A retrospective case series of operatively treated flail chest patients was compared with non-operatively treated patients. Patients' injury and treatment characteristics and outcome parameters (e.g., duration of mechanical ventilation, length of Intensive Care stay (ICLOS) and hospital length of stay (HLOS), mortality, surgery-related complications and pneumonia) were collected from the patients' medical files. Crude and matched pairs analyses were performed in SPSS. RESULTS: Twenty-three operatively and 47 non-operatively treated patients were enrolled. Operatively treated patients required significantly shorter mechanical ventilation; median 4 days versus 12 days for the non-operative group (p = 0.011). The matched-pairs analysis also showed a lower pneumonia rate (35% versus 80%; p = 0.035) and a shorter HLOS (median 21 versus 23 days; p = 0.028) in the operative group. No significant differences in duration of ICLOS, and occurrence of other injury-related adverse events were found between both groups. ?Seven surgery-related complications occurred, of which three required invasive solutions. CONCLUSIONS: Operative fixation of a flail chest in trauma patients results in a lower rate of pneumonia, less mechanical ventilation days and shorter hospital stay, compared with non-operative treatment, but at the cost of surgery-related complications requiring invasive solutions in some cases. PMID- 29785656 TI - How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions. AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are reported in the literature. Among those, the capacity to modulate the activity of T cells is by far the most often used and best-established read-out system. In this review, we critically evaluate the assays available for the functional analysis of human and murine MDSC under in vitro and in vivo conditions. We also discuss critical issues and controls associated with those assays. We aim at providing suggestions and recommendations useful for the contemporary biological characterization of MDSC. PMID- 29785654 TI - A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination. AB - BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in hospital outcome. METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered. RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use. CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients. PMID- 29785657 TI - Novel non-invasive early detection of lung cancer using liquid immunobiopsy metabolic activity profiles. AB - Lung cancer is the leading cause of cancer death worldwide. Survival is largely dependent on the stage of diagnosis: the localized disease has a 5-year survival greater than 55%, whereas, for spread tumors, this rate is only 4%. Therefore, the early detection of lung cancer is key for improving prognosis. In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations. The extracellular acidity is measured in both air-open and hermetically-sealed states, using a commercial fluorescence plate reader, for approximately 1.5 h. Both states enable the measurement of real-time accumulation of 'soluble' versus 'volatile' metabolic products, thereby differentiating between oxidative phosphorylation and aerobic glycolysis. The metabolic activity profiles are analyzed for cancer diagnosis by machine-learning tools. We present a diagnostic accuracy study, using a multivariable prediction model to differentiate between lung cancer and control blood samples. The model was developed and tested using a cohort of 200 subjects (100 lung cancer and 100 control subjects), yielding 91% sensitivity and 80% specificity in a 20-fold cross-validation. Our results clearly indicate that the proposed clinical model is suitable for non-invasive early lung cancer diagnosis, and is indifferent to lung cancer stage and histological type. PMID- 29785658 TI - Incidence and risk factors for positive urine culture at the time of pediatric urologic surgery. AB - PURPOSE: Urinary tract infections are relatively common in pediatric patients. Unrecognized bacteriuria at the time of urologic surgery puts patients at increased risk for perioperative complications. Many pediatric urologists obtain preoperative or intraoperative urine cultures prior to surgery, but data are lacking regarding rates and risk factors for positive intraoperative urine cultures. We conducted a retrospective cohort study of patients undergoing pediatric urologic surgery to examine factors associated with positive intraoperative urine cultures. MATERIALS AND METHODS: Charts of patients of age 0 18 years from a single pediatric urologist with associated intraoperative urine culture results between 2008 and 2013 were retrospectively reviewed. Demographics, prior culture results, and information regarding possible risk factors of interest-history of constipation, hydronephrosis, neurogenic bladder, posterior urethral valves, ureterocele, UPJ obstruction, urolithiasis, vesicoureteral reflux, and circumcision status-were collected and analyzed. RESULTS: Seven hundred and fifty procedure encounters with associated intraoperative urine culture results were reviewed. Overall positive urine culture rate was 13.5%. Factors associated with increased odds of positive intraoperative urine culture included neurogenic bladder (odds ratio 26.3, p < 0.001), prior positive culture (OR 5.4, p < 0.001), female sex (OR 2.1, p 0.007), constipation (OR 2.9, p < 0.001), and urolithiasis (OR 1.58, p = 0.04). Patients without any of these risk factors had no positive intraoperative cultures (p = 0.03). CONCLUSIONS: Patients with neurogenic bladder, prior positive urine culture, constipation, female gender, and urolithiasis were at increased risk for positive intraoperative urine culture. This may aid in decision-making regarding obtaining preoperative or intraoperative urine cultures in pediatric urology patients. PMID- 29785659 TI - Pyeloduodenal fistula complicating xanthogranulomatous pyelonephritis. PMID- 29785660 TI - Prevalence of hypertension and diabetes after exposure to extracorporeal shock wave lithotripsy in patients with renal calculi: a retrospective non-randomized data analysis. AB - PURPOSE: To evaluate the association of shock-wave lithotripsy (SWL) for kidney stones and hypertension or diabetes. METHODS: Patients with urolithiasis treated by SWL were retrospectively identified. To assess whether shock-wave application to the kidney is associated with long-term adverse effects, patients after SWL for kidney stones were selected as the main group of interest. Patients treated with shock waves for distal ureter stones only were chosen as a comparison group. A questionnaire was sent to all patients to assess the prevalence of hypertension and diabetes. The Swiss Health Survey (SHS) dataset was used as an additional comparison group. RESULTS: After a median follow-up of 13.7 years, the odds ratio (OR) to report hypertension [OR 1.30 (95% CI 1.10-1.95)] or diabetes [OR 1.54 (95% CI 1.21-1.97)] was significantly higher in patients treated with SWL compared to the SHS dataset. In comparison with the kidney group, participants in the SHS had a significantly lower OR to report hypertension at follow-up [OR 0.79 (95% CI 0.65-0.95)], while the OR to report hypertension [1.16 (95% CI 0.79 1.70)] was not significantly different in the distal ureter group. For diabetes, a significantly lower [OR 0.60 (95% CI 0.46-0.78)] in the SHS group and a non significantly lower [OR 0.68 (95% CI 0.38-1.22)] in the ureter group was noted compared to the kidney group. CONCLUSION: Compared to the SHS data set SWL was in general associated with hypertension and diabetes. However, no clear difference between patients after SWL to the kidney compared to SWL to the distal ureter was seen and thus the data do not support a causal relationship. PMID- 29785661 TI - Atrial fibrillation in dialysis patients: is there a place for non-vitamin K antagonist oral anticoagulants? AB - Atrial fibrillation (AF) occurs approximately in 3% of general population, with greater prevalence in elderly. Non-vitamin K-dependent oral anticoagulant agents (NOACs) according to the current European guidelines are recommended for patients with AF at high risk for stroke as a first-choice treatment. NOACs are not inferior to warfarin or some of them are better than warfarin in reducing the rate of ischemic stroke. Moreover, they significantly reduce the rate of intracranial hemorrhages, major bleedings, and mortality compared with warfarin. Nevertheless according to ESC guidelines, NOACs are not recommended in patients with creatinine clearance < 30 mL/min. Observational studies provide contradictive data. Only few new trials are ongoing. Therefore, it is not clear if NOACs should be in the future prescribed to patients with advanced CKD and those on dialysis. Moreover, the risk of stroke and bleeding is much higher in such population than in patients without end-stage renal disease (ESRD). The authors provide data on pros and cons of use of NOACs in ESRD patients with AF. PMID- 29785662 TI - The timing and circumstances of the implementation of pediatric palliative care in Hungarian pediatric oncology. AB - : Despite the continuous improvement of pediatric palliative care, medical professionals still face various barriers regarding its implementation; our aim was to investigate this question in Hungarian pediatric oncology practice. Structured interviews were carried out in person with physicians from the Hungarian Pediatric Oncology Group (n = 22). Codes were generated inductively with the aid of Atlas.ti 6.0 software. Most physicians placed the palliative care discussion at the end of curative treatment (n = 21) and preferred to conduct it in a team setting (n = 18), mainly in the presence of a psychologist. Preparing parents for the child's death can occur during the palliative care discussion (n = 3), in the child's final days/h (n = 6), gradually (n = 10), or never (n = 3). There are words consciously utilized and avoided during this discussion, with the word "death" proving to be the most ambivalent (utilized n = 5, avoided n = 6). CONCLUSIONS: There is no widely accepted unified practice among pediatric oncologists concerning the implementation of palliative care in Hungary. Despite the international recommendation, the common practice of timing is still at the end of curative treatment. Physicians rely on multidisciplinary teamwork, where the psychologist's role is the most prominent in this discussion. What is Known: * There is an international consensus that palliative care should commence at the diagnosis of a pediatric malignant disease regardless of illness outcome. * Barriers to the early implementation of palliative care in pediatric oncology involve resource-based and attitudinal factors. What is New: * In Hungary, where pediatric oncologists are sole decision-makers, early implementation of palliative care is rare. * There is a strong preference among physicians for working within a team, while also asserting that presence of team members may decrease the level of intimacy. PMID- 29785666 TI - Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis. AB - Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-kappaB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis. PMID- 29785665 TI - Why Weight? An Analytic Review of Obesity Management, Diabetes Prevention, and Cardiovascular Risk Reduction. AB - PURPOSE OF REVIEW: In this review, we examine one of the ironies of American health care-that we pay more for disease management than disease prevention. Instead of preventing type 2 diabetes (T2DM) by treating its precursor, obesity, we fail to provide sufficient insurance coverage for weight management only to fund the more costly burden of overt T2DM. RECENT FINDINGS: There is a vital need for expanded insurance coverage to help foster a weight-centric approach to T2DM management. This includes broader coverage of anti-diabetic medications with evidence of cardiovascular risk reduction and mortality benefit, anti-obesity pharmacotherapy, bariatric surgery, weight loss devices, endoscopic bariatric therapies, and lifestyle interventions for the treatment of obesity. The fundamental question to ask is why weight? Why wait to go after obesity until its end-stage sequelae cause intractable conditions? Instead of managing the complications of T2DM, consider preventing them by tackling obesity. PMID- 29785664 TI - Effect of Pneumatic Tubing System Transport on Platelet Apheresis Units. AB - Platelet apheresis units are transfused into patients to mitigate or prevent bleeding. In a hospital, platelet apheresis units are transported from the transfusion service to the healthcare teams via two methods: a pneumatic tubing system (PTS) or ambulatory transport. Whether PTS transport affects the activity and utility of platelet apheresis units is unclear. We quantified the gravitational forces and transport time associated with PTS and ambulatory transport within our hospital. Washed platelets and supernatants were prepared from platelet apheresis units prior to transport as well as following ambulatory or PTS transport. For each group, we compared resting and agonist-induced platelet activity and platelet aggregate formation on collagen or von Willebrand factor (VWF) under shear, platelet VWF-receptor expression and VWF multimer levels. Subjection of platelet apheresis units to rapid acceleration/deceleration forces during PTS transport did not pre-activate platelets or their ability to activate in response to platelet agonists as compared to ambulatory transport. Platelets within platelet apheresis units transported via PTS retained their ability to adhere to surfaces of VWF and collagen under shear, although platelet aggregation on collagen and VWF was diminished as compared to ambulatory transport. VWF multimer levels and platelet GPIb receptor expression was unaffected by PTS transport as compared to ambulatory transport. Subjection of platelet apheresis units to PTS transport did not significantly affect the baseline or agonist-induced levels of platelet activation as compared to ambulatory transport. Our case study suggests that PTS transport may not significantly affect the hemostatic potential of platelets within platelet apheresis units. PMID- 29785668 TI - Hac1p homologues from higher eukaryotes can improve the secretion of heterologous proteins in the yeast Pichia pastoris. AB - OBJECTIVES: To systematically explore the effects of overexpressing Hac1p homologues from different sources on protein secretion in Pichia pastoris system. RESULTS: Effects of Hac1p homologues encompassing P. pastoris (PpHac1p), S. cerevisiae (ScHac1p), Trichoderma reesei (TrHac1p) and Homo sapiens (HsXbp1), on secretion of three reporter proteins-beta-galactosidase, beta-mannanase and glucose oxidase were investigated. No individual Hac1p was optimal for all the enzymes. Rather, by testing a set of Hac1p, the secretory expression of each of the enzymes was improved. Notably, HsXbp1 overexpression improved beta-mannanase production from 73 to 108.5 U beta-mannanase mL-1 while PpHac1p had no impact in shake flask culture. Moreover, HsXbp1 led to 41 and 67% increases in beta mannanase production in the single- and four-copy strain, respectively in 1-L laboratory fermenter. Transcription analysis of indicative chaperones suggested that HsXbp1 may cause a stronger and prolonged activation of the UPR target chaperone genes. CONCLUSION: Mammalian HsXbp1 worked better than yeast Hac1p in terms of improving beta-mannanase secretion in P. pastoris, and Hac1p screening may offer an effective strategy to engineer the secretion pathway of eukaryotic expression systems. PMID- 29785667 TI - Cerebral Autoregulation in Stroke. AB - PURPOSE OF REVIEW: Cerebral autoregulation (CA) is a mechanism that maintains cerebral blood flow constant despite fluctuations in systemic arterial blood pressure. This review will focus on recent studies that measured CA non invasively in acute cerebrovascular events, a feature unique to the transcranial Doppler ultrasound. We will summarize the rationale for CA assessment in acute cerebrovascular disorders and specifically evaluate the existing data on the value of CA measures in relation to clinical severity, guiding management decisions, and prognostication. RECENT FINDINGS: Existing data suggest that CA is generally impaired in various cerebrovascular disorders. In patients with small vessel ischemic stroke, CA has been shown to be impaired in both hemispheres, whereas in large territorial strokes, CA impairment has been limited to the affected hemisphere. In these latter patients, impaired CA is also predictive of secondary complications such as hemorrhagic transformation and cerebral edema, hence worse functional outcome. In patients with carotid stenosis, impaired CA may also be associated with a higher ipsilateral hemispheric stroke risk. CA is also strongly linked to outcome in patients with intracranial hemorrhage. In patients with intraparenchymal hemorrhage, CA impairment correlated with clinical and imaging severity, whereas in those with subarachnoid hemorrhage, CA measures have a predictive value for development of delayed cerebral ischemia and radiographic vasospasm. Assessment of CA is increasingly more accessible in acute cerebrovascular disorders and promises to be a valuable measure in guiding hemodynamic management and predicting secondary complication, thus enhancing the care of these patients in the acute setting. PMID- 29785669 TI - Characterization of an aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea with broad substrate specificity against aromatic alcohols. AB - OBJECTIVES: The aim of the study was to obtain information about the enzymatic properties of aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea (rCcAAO), which is classified into the auxiliary activities family 3 subfamily 2 (AA3_2). RESULTS: The gene encoding AAO from the plant saprophytic basidiomycete Coprinopsis cinerea (CcAAO) was cloned, and the recombinant CcAAO (rCcAAO) was heterologously expressed in the methylotrophic yeast Pichia pastoris. The purified rCcAAO showed significant activity not only against trans,trans-2,4-hexadien-1-ol but also against a broad range of aromatic alcohols including aromatic compounds that were reported to be poor substrates for known AAOs. Moreover, site-directed mutagenesis analysis demonstrated that mutants with substitutions from leucine to phenylalanine and tryptophan at position 416 exhibited decreases of activity for aromatic alcohols but still maintained the activity for trans,trans-2,4-hexadien-1-ol. CONCLUSIONS: Leucine 416 in CcAAO contributes to the broad substrate specificity against various aromatic alcohols, which is useful for the production of hydrogen peroxide using this enzyme. PMID- 29785670 TI - Polymorphic Imprinting of SLC38A4 Gene in Bovine Placenta. AB - Imprinted genes are characterized by monoallelic expression that is dependent on parental origin. Comparative analysis of imprinted genes between species is a powerful tool for understanding the biological significance of genomic imprinting. The slc38a4 gene encodes a neutral amino acid transporter and is identified as imprinted in mice. In this study, the imprinting status of SLC38A4 was assessed in bovine adult tissues and placenta using a polymorphism-based approach. Results indicate that SLC38A4 is not imprinted in eight adult bovine tissues including heart, liver, spleen, lung, kidney, muscle, fat, and brain. It was interesting to note that SLC38A4 showed polymorphic status in five heterogeneous placentas, with three exhibiting paternal monoallelic expression and two exhibiting biallelic expression. Monoallelic expression of imprinted genes is generally associated with allele-specific differentially methylation regions (DMRs) of CpG islands (CGIs)-encompassed promoter; therefore, the DNA methylation statuses of three CGIs in the SLC38A4 promoter and exon 1 region were tested in three placentas (two exhibiting paternal monoallelic and one showing biallelic expression of SLC38A4) and their corresponding paternal sperms. Unexpectedly, extreme hypomethylation (< 3%) of the DNA was observed in all the three detected placentas and their corresponding paternal sperms. The absence of DMR in bovine SLC38A4 promoter region implied that DNA methylation of these three CGIs does not directly or indirectly affect the polymorphic imprinting of SLC38A4 in bovine placenta. This suggested other epigenetic features other than DNA methylation are needed in regulating the imprinting of bovine SLC38A4, which is different from that of mouse with respect to a DMR existence at the mouse's slc38a4 promoter region. Although further work is needed, this first characterization of polymorphic imprinting status of SLC38A4 in cattle placenta provides valuable information on investigating the genomic imprinting phenomenon itself. PMID- 29785663 TI - Enterobacteria and host resistance to infection. AB - Enterobacteriaceae are a large family of Gram-negative, non-spore-forming bacteria. Although many species exist as part of the natural flora of animals including humans, some members are associated with both intestinal and extraintestinal diseases. In this review, we focus on members of this family that have important roles in human disease: Salmonella, Escherichia, Shigella, and Yersinia, providing a brief overview of the disease caused by these bacteria, highlighting the contribution of animal models to our understanding of their pathogenesis and of host genetic determinants involved in susceptibility or resistance to infection. PMID- 29785671 TI - Agarolytic culturable bacteria associated with three antarctic subtidal macroalgae. AB - Bacterial communities of Antarctic marine macroalgae remain largely underexplored in terms of diversity and biotechnological applications. In this study, three Antarctic subtidal macroalgae (Himantothallus grandifolius, Pantoneura plocamioides and Plocamium cartilagineum), two of them endemic of Antarctica, were investigated as a source for isolation of agar-degrading bacteria. A total of 21 epiphytic isolates showed agarolytic activity at low temperature on agar plates containing agar as the sole carbon source. 16S rRNA identification showed that the agar-degrading bacteria belonged to the genera Cellulophaga, Colwellia, Lacinutrix, Olleya, Paraglaciecola, Pseudoalteromonas and Winogradskyella. The agarase enzyme from a potential new species of the genus Olleya was selected for further purification. The enzyme was purified from the culture supernatant of Olleya sp. HG G5.3 by ammonium sulfate precipitation and ion-exchange chromatography. Molecular weight of the agarase was estimated to be 38 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified enzyme exhibited activity at 4 degrees C, retaining > 50% of its maximum activity at this temperature. This is the first study reporting the phylogeny of agar-degrading bacteria isolated from Antarctic subtidal macroalgae and the results suggest the huge potential of Antarctic algae-associated bacteria as a source of cold-active hydrolytic enzymes of biotechnological interest. PMID- 29785672 TI - Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus. AB - To assess T cell subsets and levels of chemokines and cytokines in patients with SLE and determine their relationships between disease activity and organ involvement. Blood samples from SLE patients (n = 24) and healthy controls (n = 36) were analyzed. Frequency of circulating follicular help T cells (Tfh), central memory T cells (Tcm), effector memory T cells (Tem), and naive T cell subsets was enumerated and their surface markers expression of inducible T cell co-stimulator (ICOS) and programmed death 1(PD-1) protein was examined by flow cytometry. The disease state in SLE patients was evaluated using the SLE Disease Activity Index (SLEDAI). Concentrations of autoantibodies, serum C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), lgG, complement 3, complement 4, cytokines, and chemokines, such as IL-21, IL-17A, and IL-1beta, were measured. The frequencies of circulating Tfh and Tcm cell subsets were significantly lower than those in healthy controls. However, the percentages of circulating PD1+ICOS+Tfh, PD1+ICOS+Tcm, and PD1+ICOS+Tem of PBMCs from SLE patients were higher than those in healthy controls. Furthermore, increased levels of serum IL-1beta, IL-4, IL-6, MCP-1, IL-21, and IL-17A were detected in the patients with SLE compared to healthy controls. In addition, patients with immune thrombocytopenia displayed elevated proportions of serum IL-10, IL-17A, and IL-1beta. Aberrant T cell subsets and cytokines expression profile were observed in SLE patients. PD1+ICOS+Tem cell subset was clearly influenced by disease activity and serum IL-10, IL-17A, and IL-1beta were significantly increased in patients with immune thrombocytopenia. Therefore, PD1+ICOS+Tem cells might serve as an important tool for recognition and serum IL-10, IL-17A, and IL 1beta might be an effective monitor for SLE patients with immune thrombocytopenia. PMID- 29785673 TI - The Impact of Transcranial Direct Current Stimulation (tDCS) on Bipolar Depression, Mania, and Euthymia: a Systematic Review of Preliminary Data. AB - The neurobiological basis of bipolar disorders (BD) has received increased attention and several brain regions and brain circuits have been correlated with clinical symptoms. These brain regions and circuits may represent targets for neuromodulation techniques such as transcranial Direct Current Stimulation (tDCS). We systematically reviewed the literature to explore the risks and benefits of tDCS in BD and examined all mood states. Following the PRISMA guidelines, a systematic literature search using several databases was performed from April 2002 to June 2017. From the 135 eligible studies, we retained 19 relevant articles for the systematic review, including 170 patients with BD treated by tDCS. Data from 10 studies suggest that tDCS improves depressive symptoms in BD. One case report of add-on-tDCS reported a significant positive response on manic symptoms. In 4 studies, tDCS impacted specific neurocognitive functions in euthymic patients. There is also preliminary evidence that tDCS improves neurological soft signs and sleep quality in euthymia. Side effects were predominantly transient and low-intensity, although 6 cases of hypomanic/manic affective switches have been reported. The majority of studies have been open trials with few patients. More sufficiently powered randomized controlled trials are needed to clarify the effectiveness of tDCS. Preliminary data suggests that tDCS holds promise as a treatment for BD, especially during depressive episodes. Perhaps most promising are emerging data suggesting tDCS may impact neurocognition and sleep quality in euthymia and be useful for relapse prevention. PMID- 29785675 TI - Transfusion triggers in cardiac surgery: Where do we go from here? PMID- 29785674 TI - Assembly of a complete genome sequence for Gemmata obscuriglobus reveals a novel prokaryotic rRNA operon gene architecture. AB - Gemmata obscuriglobus is a Gram-negative bacterium with several intriguing biological features. Here, we present a complete, de novo whole genome assembly for G. obscuriglobus which consists of a single, circular 9 Mb chromosome, with no plasmids detected. The genome was annotated using the NCBI Prokaryotic Genome Annotation pipeline to generate common gene annotations. Analysis of the rRNA genes revealed three interesting features for a bacterium. First, linked G. obscuriglobus rrn operons have a unique gene order, 23S-5S-16S, compared to typical prokaryotic rrn operons (16S-23S-5S). Second, G. obscuriglobus rrn operons can either be linked or unlinked (a 16S gene is in a separate genomic location from a 23S and 5S gene pair). Third, all of the 23S genes (5 in total) have unique polymorphisms. Genome analysis of a different Gemmata species (SH PL17), revealed a similar 23S-5S-16S gene order in all of its linked rrn operons and the presence of an unlinked operon. Together, our findings show that unique and rare features in Gemmata rrn operons among prokaryotes provide a means to better define the evolutionary relatedness of Gemmata species and the divergence time for different Gemmata species. Additionally, these rrn operon differences provide important insights into the rrn operon architecture of common ancestors of the planctomycetes. PMID- 29785676 TI - Asymmetry of the greater cornua of the hyoid bone and the superior thyroid cornua: a case report. AB - The hyoid bone consists of a body and two pairs of processes: the greater cornua (GC) and the lesser cornua. The GC is connected to the superior thyroid cornu (STC) by the lateral thyrohyoid ligament. The GC and the STC share a common embryological origin from the third pharyngeal arch. During anatomical dissection of a male cadaver of 56 years of age, a combined variation of the GC and the STC was found. The left GC was 27.7 mm long, and the right GC was 30 mm long. The left GC axis was in the same plane as the hyoid body, while an angle of 33 degrees was between the right GC axis and the hyoid body plane. The left STC was 17.6 mm long, and the right STC was 25.8 mm long. The angle of left STC medial inclination was 70 degrees , while the right STC was perpendicular to the horizontal plane of the larynx. Anatomical variations of the hyoid bone and the laryngeal cartilages have possible clinical implications, such as Eagle syndrome and the STC syndrome. The case we described may inspire the anatomists to research the occurrence of combined variations of the larynx and the hyoid bone. PMID- 29785677 TI - Analysis of the frequency of visualization of morphological variations in anatomical bone features in the mandibular interforaminal region through cone beam computed tomography. AB - PURPOSE: The purpose of this study was to analyze the frequency of visualization of anatomical bone features and their possible variations in the mandibular interforaminal region through cone-beam computed tomography (CBCT). METHODS: This is a cross-sectional study that evaluated CBCT scans of the mandible of 141 women and 61 men, obtained by imaging archives from two private clinics of dental radiology. The study analyzed the frequency of visualization of: lingual symphyseal foramen (LSF), additional mental foramen (AdMF), absence of mental foramen (AbMF), mandibular incisive canal (MIC), and anterior loop (AL). Length measurements for MIC and AL were determined at first and following that the respective distances towards vestibular and lingual cortical walls were also individually verified. Statistical analyses included: Student's t test, Chi square test, and ANOVA for the evaluation of the anatomical features observed through panoramic and parasagittal images' reconstructions. RESULTS: LSF presence was found in 97%, MIC in 75.9%, AL in 24%, AdMF in 4.7%, and AbMF in 2.5%. Chi square tests demonstrated value results of p < 0.05 only for the presence of left AL in women when compared to men. Mean values for length measures of MIC and AL were of 10.1 and 2.12 mm, respectively. Mean distance from AL towards vestibular and lingual cortical walls was of 2.53 and 4.05 mm, respectively. CONCLUSION: Anatomical variability concerning the mandibular interforaminal region emphasizes the importance of performing CBCT in pre-operative assessment of the mandible for surgical procedures with oral implants. PMID- 29785678 TI - Heterotopic pancreas without Meckel's diverticulum in children as unique cause of gastrointestinal bleeding: think about it! AB - Ectopic pancreas also known as heterotopic pancreas (HP) is a rare congenital anomaly, mainly found as incidental finding during autopsy or abdominal exploration for an other condition. Incidence rate is probably underestimated as patients are mostly asymptomatic; otherwise, it is capable of producing symptoms depending on its location, size, often appearing in the 4th-to-6th decades. Complications such as inflammation, obstruction, bleeding, and malignancy degeneration must be considered. Pediatrics cases are very rare, generally concerning HP within Meckel's diverticulum, manifesting by gastrointestinal bleeding and intussusception. We report a rare case of jejunum bleeding, due to an isolated HP in a 15-year-old adolescent. Endoscopic and computed tomographic scan were normal, in particular did not found Meckel's diverticulum. Diagnosis and treatment have been apprehended performing a laparoscopic exploration. It is a singular location for HP, predominantly found in upper gastrointestinal tractus. So far, there have been no case reports of jejunal bleeding from ectopic pancreas without Meckel's diverticulum in children. PMID- 29785680 TI - An Unusual Case of Heartburn and Esophageal Stenosis. PMID- 29785679 TI - Drooling in Parkinson's Disease: Evidence of a Role for Divided Attention. AB - Drooling is a frequently reported symptom in Parkinson's Disease (PD) with significant psychosocial impact and negative health consequences including silent aspiration of saliva with the associated risk of respiratory infections. It is suggested that in PD drooling is associated with inefficient oropharyngeal swallowing which reduces the effective clearance of saliva rather than hyper salivation. This is compounded by unintended mouth opening and flexed posture increasing anterior loss of saliva. It is reported to occur most frequently during cognitively distracting concurrent tasks suggesting an impact from divided attention in a dual-task situation. However, this supposition has not been systematically examined. This study assessed whether frequency of saliva swallows reduced, and drooling severity and frequency increased, when people with PD engaged in a cognitively distracting task. 18 patients with idiopathic PD reporting daytime drooling on the Unified Parkinson's Disease Rating Scale (UPDRS) were recruited. They completed the Radboud Oral Motor Inventory for PD saliva questionnaire and the Montreal Cognitive Assessment. UPDRS drooling score, disease stage, duration, gender, and age were recorded. Swallow frequency and drooling severity and frequency were measured at rest and during a distracting computer-based language task. There was no significant difference between drooling severity at rest and during distraction (Wilcoxon signed rank test z = - 1.724, p = 0.085). There was a significant difference between at rest and distraction conditions for both drooling frequency (Wilcoxon signed rank test z = - 2.041, p = 0.041) and swallow frequency (Wilcoxon signed rank test z = - 3.054, p = 0.002). Participants swallowed less frequently and drooled more often during the distraction task. The frequency of saliva swallows and drooling are affected by divided attention in a dual-task paradigm. Further studies are needed to explore the exact role of attention in saliva management and the clinical applications in assessment and treatment. PMID- 29785682 TI - The modified Memorial Symptom Assessment Scale Short Form: a modified response format and rational scoring rules. AB - PURPOSE: The Memorial Symptom Assessment Scale Short Form (MSAS-SF) is a widely used symptom assessment instrument. Patients who self-complete the MSAS-SF have difficulty following the two-part response format, resulting in incorrectly completed responses. We describe modifications to the response format to improve useability, and rational scoring rules for incorrectly completed items. METHODS: The modified MSAS-SF was completed by 311 women in our Peer and Nurse support Trial to Assist women in Gynaecological Oncology; the PeNTAGOn study. Descriptive statistics were used to summarise completion of the modified MSAS-SF, and provide symptom statistics before and after applying the rational scoring rules. Spearman's correlations with the Functional Assessment for Cancer Therapy-General (FACT-G) and Hospital Anxiety and Depression Scale (HADS) were assessed. RESULTS: Correct completion of the modified MSAS-SF items ranged from 91.5 to 98.7%. The rational scoring rules increased the percentage of useable responses on average 4% across all symptoms. MSAS-SF item statistics were similar with and without the scoring rules. The pattern of correlations with FACT-G and HADS was compatible with prior research. CONCLUSION: The modified MSAS-SF was useable for self completion and responses demonstrated validity. The rational scoring rules can minimise loss of data from incorrectly completed responses. Further investigation is recommended. PMID- 29785681 TI - Diabetes symptoms predictors of health-related quality of life in adolescents and young adults with type 1 or type 2 diabetes. AB - OBJECTIVES: The objective was to investigate the patient-reported diabetes symptoms predictors of generic health-related quality of life (HRQOL) in adolescents and young adults (AYA) with type 1 or type 2 diabetes. METHODS: The 15-item PedsQLTM 3.2 Diabetes Module Diabetes Symptoms Summary Score and PedsQLTM 4.0 Generic Core Scales were completed in a 10-site national field test study by 513 AYA ages 13-25 years with type 1 (n = 424) or type 2 (n = 89) diabetes. Diabetes symptoms were tested for bivariate and multivariate linear associations with generic HRQOL. RESULTS: Diabetes symptoms were associated with decreased HRQOL in bivariate analyses. In predictive analytics models utilizing hierarchical multiple regression analyses controlling for relevant demographic and clinical covariates, diabetes symptoms accounted for 38 and 39% of the variance in patient-reported generic HRQOL for type 1 and type 2 diabetes, respectively, reflecting large effect sizes. The diabetes symptoms facets hyperglycemia symptoms, hypoglycemia symptoms, and nonspecific diabetes symptoms individually accounted for a significant percentage of the variance in separate exploratory predictive analytics models after controlling for demographic and clinical covariates, with small-to-large effect sizes. CONCLUSIONS: Diabetes symptoms are potentially modifiable predictors of generic HRQOL in AYA with diabetes. Identifying specific diabetes symptoms or symptoms facets that are the most important predictors from the patient perspective facilitates a patient centered approach in clinical research, clinical trials, and practice designed to enhance overall generic HRQOL in AYA with diabetes. PMID- 29785683 TI - Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance. AB - Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (>= 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist. PMID- 29785684 TI - Impact of a clinical decision support system for drug dosage in patients with renal failure. AB - Background A clinical decision support system (CDSS) linked to the computerized physician order entry may help improve prescription appropriateness in inpatients with renal insufficiency. Objective To evaluate the impact on prescription appropriateness of a CDSS prescriber alert for 85 drugs in renal failure patients. Setting Before-after study in a 975-bed academic hospital. Method Prescriptions of patients with renal failure were reviewed during two comparable periods of 6 days each, before and after the implementation of the CDSS (September 2009 and 2010). Main outcome measure The proportion of inappropriate dosages of 85 drugs included in the CDSS was compared in the pre- and post implementation group. Results Six hundred and fifteen patients were included in the study (301 in pre- and 314 in post-implementation periods). In the pre- and post-implementation period, respectively 2882 and 3485 prescriptions were evaluated, of which 14.9 and 16.6% triggered an alert. Among these, the dosage was inappropriate in respectively 25.4 and 24.6% of prescriptions in the pre- and post-implementation periods (OR 0.97; 95% CI 0.72-1.29). The most frequently involved drugs were paracetamol, perindopril, tramadol and allopurinol. Conclusion The implementation of a CDSS did not significantly reduce the proportion of inappropriate drug dosages in patients with renal failure. Further research is required to investigate the reasons why prescribers override alerts. Collaboration with clinical pharmacists might improve compliance with the CDSS recommendations. PMID- 29785685 TI - Network meta-analysis: an introduction for pharmacists. AB - Network meta-analysis is a new tool used to summarize and compare studies for multiple interventions, irrespective of whether these interventions have been directly evaluated against each other. Network meta-analysis is quickly becoming the standard in conducting therapeutic reviews and clinical guideline development. However, little guidance is available to help pharmacists review network meta-analysis studies in their practice. Major institutions such as the Cochrane Collaboration, Agency for Healthcare Research and Quality, Canadian Agency for Drugs and Technologies in Health, and National Institute for Health and Care Excellence Decision Support Unit have endorsed utilizing network meta analysis to establish therapeutic evidence and inform decision making. Our objective is to introduce this novel technique to pharmacy practitioners, and highlight key assumptions behind network meta-analysis studies. PMID- 29785687 TI - Education Is Associated with the Magnitude of Cortisol Responses to Psychosocial Stress in College Students. AB - PURPOSE: Researchers benefit from controlling for individual differences that systematically account for variance in acute cortisol responses (e.g., sex). Similarly, some suggest that education could be used as a cortisol covariate because prior work found a negative relationship between education and the magnitude of acute cortisol responses in middle-aged adults. Nevertheless, education is seldom controlled for in tests of cortisol responses to acute stress, in part because the effect of education on acute cortisol responses has yet to be tested in a college sample. The present study therefore tested the relationship between education and cortisol responses to acute stress in college students. METHOD: Participants (124 healthy undergraduate students) self-reported education level and were subjected to a stressful speech task. Salivary cortisol was collected 0, + 15, + 25, + 40, and + 55 min post-stressor onset. Participant also completed a battery of questionnaires assessing individual differences, day to-day demands, and stress-related appraisals. RESULTS: Students in their fourth year of college education or above had significantly less curvilinear responses to the stress task relative to first-, second-, and third-year students. CONCLUSION: The effect of education on cortisol responses previously found in middle-aged adults was replicated in college students. Future research may therefore benefit from controlling for education when analyzing acute cortisol responses in college samples. PMID- 29785686 TI - Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study. AB - PURPOSE: Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. METHODS: Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. RESULTS: Metoprolol specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. CONCLUSIONS: Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs. PMID- 29785688 TI - The Influence of Nonionic Surfactant Adsorption on Enzymatic Hydrolysis of Oil Palm Fruit Bunch. AB - Nonionic surfactants have been utilized to improve the enzymatic hydrolysis of lignocellulosic materials. However, the role of surfactant adsorption affecting enzymatic hydrolysis has not been elaborated well. In this work, nonionic surfactants differing in their molecular structures, namely the polyoxyethylene sorbitan monooleate (Tween 80), the secondary alcohol ethoxylate (Tergitol 15-S 9), and the branched alcohol ethoxylate (Tergitol TMN-6), were studied for their effects on the enzymatic hydrolysis of palm fruit bunch (PFB). The PFB was pretreated with a 10% w/v sodium hydroxide solution and then hydrolyzed using the cellulase enzyme from Trichoderma reesei (ATCC 26921) at 50 degrees C and pH 5. The optimal conditions providing similar yields of reducing sugar required Tween 80 and Tergitol TMN-6 at 0.25% w/v, while Tergitol 15-S-9 was required at 0.1% w/v. All the surfactants improved the enzymatic conversion efficiency and reduced unproductive binding of the enzyme to lignin. In addition, the adsorption isotherm of cellulase was fit well by the Freundlich isotherm, while adsorption of the three nonionic surfactants agreed well with the Langmuir isotherm. Adsorption capacities of the three nonionic surfactants were consistent with their enhancement efficiencies in hydrolysis. The critical micelle concentration was observed as a key property of nonionic surfactant for adsorption capacity. PMID- 29785689 TI - The Impact of Hospital Costing Methods on Cost-Effectiveness Analysis: A Case Study. AB - BACKGROUND: Several methods exist to cost hospital contacts when estimating the cost effectiveness of a new intervention. However, the implications of choosing a particular approach remain unclear. We compare the use of the three main diagnosis-related group (DRG)-based national unit costs in England to determine whether choice of approach can impact on economic evaluation results. METHODS: A cost-utility model was developed to compare secondary fracture prevention models of care for hip fracture patients, using data from large primary and hospital care administrative datasets in England. A healthcare and personal social services payer perspective was adopted, and utilities were informed by a meta regression. Hospital resource use was valued using three DRG-based unit costs, and regression-based costing models were developed using data from 13,906 patients to inform the model health states. RESULTS: Finished consultant episode (FCE)-level reference costs resulted in the highest costs on admission (L9075) and in the year of the fracture (L14,440). Relative to FCE-level costs, spell level tariffs led to the lowest total hospital care costs per patient within 1 year of fracture (- L3691) compared with spell-level reference costs (- L2106). At a L20,000/quality-adjusted life-year threshold, using spell-level reference costs or spell-level tariffs, the introduction of a nurse-led fracture liaison service model of care was the cost-effective alternative. However, using FCE level reference costs, usual care was the cost-effective option. CONCLUSIONS: Our results show that, conditional on the set of national unit costs adopted, the costs of hip fracture may vary considerably and different decisions may be reached regarding the introduction of new healthcare interventions. PMID- 29785691 TI - Psychometric Properties of the Multidimensional Loss Scale with Refugee Women-at Risk Recently Arrived in Australia. AB - Refugee women-at-risk represent a distinct and vulnerable refugee population. We investigated the psychometric properties of the Multidimensional Loss Scale (MLS) with 104 women-at-risk, recently-arrived in Australia. Cross-sectional survey included: the MLS (indexing loss events and loss distress); Harvard Trauma Questionnaire (Indexing Trauma Events and Trauma Symptoms), and; Hopkins Symptom Checklist-37 (indexing anxiety, depression, and somatization symptoms). Exploratory factor analyses of MLS loss distress revealed a six-factor model (loss of symbolic self; loss of home; loss of interdependence; loss of past aspirations; interpersonal loss, and; loss of intrapersonal integrity). Cronbach alphas indicated satisfactory internal consistency for loss events (0.83) and distress (0.88). Correlations supported convergent validity of loss distress with trauma symptoms (r = 0.41) and divergent validity with anxiety (r = 0.09), Depression (r = 0.29), and somatic (r = 0.24) symptoms. Findings support MLS use in assessment of loss and associated distress with refugee women-at-risk. PMID- 29785690 TI - Migrant Healthcare Guidelines: A Systematic Quality Assessment. AB - Significant international and cross-border migration has led to a growing availability of migrant healthcare guidelines (MHGs), which we systematically reviewed for quality. PubMed, MEDLINE, CINHAL, PsychINFO and guideline developer/guideline databases were searched for MHGs published 2006-2016. Three independent reviewers assessed eligible MHGs using the Appraisal of Guidelines, Research and Evaluation II instrument (AGREE II). MHGs were identified as high quality if they had a score of >= 60% in at least three of the six domains, including "rigour of development", and overall quality was assessed on a seven point Likert scale. We included 32 MHGs. Overall agreement between reviewers was very good. Mean scores for each AGREE II domain were as follows: 85 +/- 19.0% for "scope and purpose"; 51 +/- 30.5% for "stakeholder involvement"; 34 +/- 31.9% for "rigour of development"; 86 +/- 7.3% for "clarity of presentation"; 40 +/- 23.6% for "applicability"; and 27 +/- 38.5% for "editorial independence". Nine and six MHGs were deemed "recommended" or "recommended with modifications", respectively, and 17 were "not recommended". Our review of MHGs has highlighted critical deficiencies in rigour of development, applicability, editorial independence and stakeholder involvement that point to the need for improvements in future MHGs. PMID- 29785692 TI - Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation. AB - BACKGROUND: Infection is a leading cause of death after liver transplantation (LT). Therefore, prevention of infection is crucial for improving outcomes after LT. We examined the impact of early enteral nutrition with an immunomodulating diet (IMD) enriched with hydrolyzed whey peptide (HWP) formulation on infection after living donor LT (LDLT), focusing on sarcopenia. METHODS: This study enrolled 279 consecutive patients who underwent primary LDLT at our institute between January 2008 and April 2015. Early enteral nutrition with the IMD enriched with HWP formulation and a conventional elemental diet were started within the first 24 h after surgery for 164 (IMD-HWP) and 115 (conventional) patients. Sequential changes in nutritional parameters, and the incidences of acute cellular rejection (ACR) and bacteremia were compared between the IMD-HWP and control groups. The comparison was made between those members of each group that did or did not exhibit sarcopenia. Risk factors for post-transplant bacteremia were also assessed. RESULTS: Postoperative nutritional parameters and the incidence of ACR were comparable between the groups, except for the prealbumin level. The incidence of bacteremia was significantly lower in the IMD HWP group, and among patients without sarcopenia in the IMD-HWP group compared with the conventional group (24.4 vs. 41.7%; P = 0.002 and 20.8 vs. 39.0%; P = 0.040, respectively). Independent risk factor for bacteremia comprised bleeding >=10,000 mL (P = 0.025). In contrast, enteral nutrition without HWP formulation was not significantly associated with bacteremia. However, enteral nutrition without HWP formulation (P = 0.080), MELD scores (P = 0.097), and ABO incompatibility (P = 0.088) showed a trend toward increased incidence of bacteremia, although they did not reach statistical significance in the multivariate analysis. CONCLUSION: Postoperative immunonutrition with an IMD enriched with HWP formulation was closely involved with post-transplant bacteremia. PMID- 29785693 TI - Massive Transfusion: The Revised Assessment of Bleeding and Transfusion (RABT) Score. AB - BACKGROUND: Massive transfusion (MT) is a lifesaving treatment for trauma patients with hemorrhagic shock, assessed by Assessment of Blood Consumption (ABC) Score based on mechanism of injury, systolic blood pressure (SBP), tachycardia, and FAST exam. The aim of this study was to assess the performance of ABC score by replacing hypotension and tachycardia; with Shock Index (SI) > 1.0 and including pelvic fractures. METHODS: We performed a 2-year (2014-2015) analysis of all high-level trauma activations and excluded patients dead on arrival. The ABC score was calculated using the 4-point score [blunt (0)/penetrating trauma (1), HR >= 120 (1), SBP <= 90 mmHg (1), and FAST positive (1)]. The Revised Assessment of Bleeding and Transfusion (RABT) score also included 4 points, calculated by replacing HR and SBP with SI > 1.0 and including pelvic fracture. AUROC compared performances of the two scores. RESULTS: A total of 380 patients were included. The overall MT was 27%. Patients receiving MT had higher median ABC scores [1.1 (0-2) vs. 1 (0-2), p = 0.15] and RABT scores [2 (1 3) vs. 1 (0-2), p < 0.001]. The RABT score had better discriminative power (AUROC = 0.828) compared to ABC score (AUROC = 0.617) for predicting the need for MT. Cutoff of RABT score >= 2 had a sensitivity of 84% and specificity of 77% for predicting need for MT compared to ABC score with 39% sensitivity and 72% specificity. CONCLUSION: Replacement of hypotension and tachycardia with a SI > 1.0 and inclusion of pelvic fracture enhanced discrimination of ABC score for predicting the need for MT. The current ABC score would benefit from revision to more appropriately identify patients requiring MT. PMID- 29785694 TI - Surgical Capacity at District Hospitals in Zambia: From 2012 to 2016. AB - BACKGROUND: Sub-Saharan Africa has one of the highest burdens of surgically treatable conditions in the world and the highest unmet need, especially in rural areas. Zambia is one of the countries in the region taking steps to improve surgical care for its rural populations. AIM: To demonstrate changes in surgical capacity in Zambia's district hospitals over a 3-year period and to provide a baseline from which future interventions in surgical care can be assessed. METHODS: A cross-sectional assessment of surgical capacity, using a modified WHO questionnaire, was administered in first-level hospitals in nine of Zambia's ten provinces between November 2012 and February 2013 and again between February and April 2016. The two assessments allowed measurement of changes in surgical workforce, infrastructure, equipment, drugs and consumables; and numbers of major surgical procedures performed over two 12-month periods prior to the assessments. RESULTS: There was a significant increase, 2013-2016, in number of theatre staff, from 174 (mean 4.4; SD 1.7) to 235 (mean 6; SD 2.9), P = 0.02. However, the percentage of hospitals with functioning anaesthetic machines dropped from 64 to 41%. There was also a drop in hospitals reporting availability of instruments, drugs and consumables from 38 to 24 (97-62%) and from 28 to 24 (72-62%), respectively. The median number of caesarean sections in 2012 was 99 [interquartile range (IQR) 42-187] and 100 (IQR 42-126) in 2015 (P value =0.53). The median number of major surgical procedures in 2012 was 54 (IQR 10-113) and 66 (IQR 18-168) in 2015 (P = 0.45). CONCLUSION: An increase in the first-level hospital surgical workforce between 2013 and 2016 was accompanied by reductions in essential equipment and consumables for surgery, and no changes in surgical output. Periodic monitoring of resource availability is needed to address shortages and make safe surgery available to rural populations. PMID- 29785696 TI - Case-Matched Comparison of Long-Term Functional and Quality of Life Outcomes Following Laparoscopic Versus Open Ileal Pouch-Anal Anastomosis. AB - BACKGROUND: Laparoscopic ileal pouch-anal anastomosis (IPAA) is associated with recovery benefits when compared with open IPAA. There is limited data on long term quality of life and functional outcomes, which this study aimed to assess. METHODS: An IRB-approved, prospectively maintained database was queried to identify patients undergoing laparoscopic IPAA (L), case-matched with open IPAA (O) based on age +/- 5 years, gender, body mass index (BMI) +/- 5 kg/m2, diagnosis, date of surgery +/- 3 years, stapled/handsewn anastomosis, omission of diverting loop ileostomy and length of follow-up +/- 3 years. We assessed functional results, dietary, social, work, sexual restrictions and the Cleveland Clinic global quality of life score (CGQoL) at 1, 2, 3, 4, 5 and 10 years postoperatively. Functional outcomes were assessed based on number of stools (day/night) and seepage protection use (day/night). Variables were evaluated with Kaplan-Meier survival curves, uni- and multivariable analyses. RESULTS: Out of 4595 IPAAs, 529 patients underwent L, of whom 404 patients were well matched 1:1 to an equivalent number of O based on all criteria. Median follow-ups were 2 (0.5 17.8) versus 2.4 (0.5-22.2) years in L versus O, respectively (p = 0.18). L was associated with significantly decreased number of stools at night and less frequent pad usage at 1 year, both during the day and at night. Functional outcomes became similar during further follow-up. L was also associated with improved overall CGQoL, and energy scores at 1 year postoperatively, and decreased social restrictions for 1-2 years. There were no significant differences in quality of health, dietary, work or sexual restrictions. Laparoscopy was not associated with increased risk of pouch failure (p = 0.07) or significantly different causes of pouch failure when compared to O. CONCLUSIONS: Laparoscopic and open IPAA are associated with equivalent long-term functional outcomes, quality of life and pouch survival rates. Laparoscopic technique is associated with temporary benefits lasting 1 or 2 years. PMID- 29785695 TI - Differences in Characteristics and Outcome of Patients with Penetrating Injuries in the USA and the Netherlands: A Multi-institutional Comparison. AB - INTRODUCTION: The incidence and nature of penetrating injuries differ between countries. The aim of this study was to analyze characteristics and clinical outcomes of patients with penetrating injuries treated at urban Level-1 trauma centers in the USA (USTC) and the Netherlands (NLTC). METHODS: In this retrospective cohort study, 1331 adult patients (470 from five NLTC and 861 from three USTC) with truncal penetrating injuries admitted between July 2011 and December 2014 were included. In-hospital mortality was the primary outcome. Outcome comparisons were adjusted for differences in population characteristics in multivariable analyses. RESULTS: In USTC, gunshot wound injuries (36.1 vs. 17.4%, p < 0.001) and assaults were more frequent (91.2 vs. 77.7%, p < 0.001). ISS was higher in USTC, but the Revised Trauma Score (RTS) was comparable. In hospital mortality was similar (5.0 vs. 3.6% in NLTC, p = 0.25). The adjusted odds ratio for mortality in USTC compared to NLTC was 0.95 (95% confidence interval 0.35-2.54). Hospital stay length of stay was shorter in USTC (difference 0.17 days, 95% CI -0.29 to -0.05, p = 0.005), ICU admission rate was comparable (OR 0.96, 95% CI 0.71-1.31, p = 0.80), and ICU length of stay was longer in USTC (difference of 0.39 days, 95% CI 0.18-0.60, p < 0.0001). More USTC patients were discharged to home (86.9 vs. 80.6%, p < 0.001). Readmission rates were similar (5.6 vs. 3.8%, p = 0.17). CONCLUSION: Despite the higher incidence of penetrating trauma, particularly firearm-related injuries, and higher hospital volumes in the USTC compared to the NLTC, the in-hospital mortality was similar. In this study, outcome of care was not significantly influenced by differences in incidence of firearm-related injuries. PMID- 29785697 TI - The Video-Assisted Thoracic Surgery for Mediastinal Bronchogenic Cysts: A Single Center Experience. AB - OBJECTIVE: The aim of this study was to evaluate the outcomes of video-assisted thoracic surgery (VATS) for mediastinal bronchogenic cyst (MBC) excision and investigate the surgical indication for MBC. METHODS: We retrospectively reviewed all consecutive MBC patients who underwent surgical excision between April 2001 and June 2016. One hundred and nineteen patients were enrolled with a median age of 45.4 years and divided into two groups: anterior mediastinum group (n = 48), and middle and posterior mediastinum group (n = 71). VATS technique was initially performed for each patient. The cyst should be resected completely as far as possible. Follow-up was completed by telephone or outpatient clinic every year. The deadline of follow-up was June 2017. RESULTS: One hundred and eighteen patients underwent VATS, and only one patient converted to open thoracotomy. The average operative time was 103.8 +/- 41.6 min (40-360 min). The average intraoperative blood loss was 56.6 +/- 86.6 ml (5-600 ml). The intraoperative complication rate was 3.4%, and the incomplete excision rate was 5.9%. The multivariate logistic analysis showed that maximal diameter >5 cm was significantly associated with risk of operation time extension (OR = 3.968; 95% CI 1.179-13.355, p = 0.026) and bleeding loss increasing (OR = 12.242; 95% CI 2.420-61.933, p = 0.002). No serious postoperative complications were observed. Follow-up was performed in 102 patients, and the mean follow-up time was 45 months (12-194 months). There was no local recurrence. CONCLUSIONS: The maximal diameter >5 cm increased risk of operation time extension and bleeding loss increasing. Early surgical excision of MBC by VATS is recommended to establish histopathological diagnosis, relieve symptoms, and prevent surgery-related complications. PMID- 29785698 TI - Specific parasites indirectly influence niche occupation of non-hosts community members. AB - The coexistence of phylogenetically related species is an attractive topic because of the potentially intense interspecific competition. The most often investigated mechanisms mediating coexistence of these species are environmental filtering and niche partitioning. However, the role of other factors, such as species-specific parasites, is still poorly understood. Along the riparian understory of a tropical forest, we explored niche occupation and coexistence between Chrysso intervales and Helvibis longicauda, two related syntopic web building spiders. We also investigated the effect of H. longicauda mortality induced by a specific fungus parasite, Gibellula pulchra, on the dynamic of C. intervales spatial distribution. Coexistence was mediated mainly by a fine-scale horizontal spatial segregation. H. longicauda built webs almost exclusively close to the river, while C. intervales occupied adjacent areas (10-20 m away from margins). We also found differentiation in other niche dimensions that might allow coexistence, such as in plants occupied, height of web placement, width of leaves used for thread attachment and phenology. H. longicauda mortality caused by fungi was higher during winter than in summer. Consequently, the abundance of C. intervales increased at distances close to the river, indicating competitive release through a density-mediated indirect effect. This demonstrates how non competitive specific-antagonists can indirectly affect other non-hosts competing community members and influence their spatial distribution in fine-scale ranges. We suggest that environmental filtering restricts H. longicauda to cooler regions; niche partitioning leads populations to occupy different vertical strata and competitive exclusion precludes C. intervales to reach river margins, generating an unusual horizontal zonation pattern. PMID- 29785699 TI - Spectroscopic Analysis of the Cu2+-Induced Fluorescence Quenching of Fluorescent Proteins AmCyan and mOrange2. AB - Fluorescent proteins show fluorescence quenching by specific metal ions, which can be applied towards metal biosensing applications. In order to develop metal biosensor, we performed spectroscopic analysis of the fluorescence quenching of fluorescent protein AmCyan and mOrange2 by various metal ions. The fluorescence intensity of AmCyan was reduced to 48.54% by Co2+ and 67.77% by Zn2+; Cu2+ reduced the fluorescence emission of AmCyan to 19.30% of its maximum. The fluorescence intensity of mOrange2 was quenched by only Cu2+, to 11.48% of its maximum. When analyzed by Langmuir equation, dissociation constants for AmCyan and mOrange2 were 56.10 and 21.46 uM, respectively. The Cu2+ quenching of AmCyan and mOrange2 were reversible upon treatment with the metal chelator EDTA, indicating that the metal ions were located on the protein surface. Their model structures suggest that AmCyan and mOrange2 have novel metal-binding sites. PMID- 29785701 TI - Botulin toxin injection to improve the results of sphincter overlap in high grade obstetric anal sphincter injury syndrome. PMID- 29785700 TI - The association between circulating irisin levels and different phenotypes of polycystic ovary syndrome. AB - PURPOSE: The diagnosis of polycystic ovary syndrome (PCOS) is based on a combination of various clinical phenotypes in each patient. However, insulin resistance (IR) and dysmetabolism are not included in the diagnostic criteria of PCOS. Therefore, the definition of PCOS is controversial. The objective of this study is to investigate whether some PCOS phenotypes can be predicted by a circulating biomarker related to IR and metabolic dysfunction in PCOS women. METHODS: One hundred and seventeen women with PCOS and 95 healthy women were recruited for this study. All individuals were assessed by the phenotypic and metabolic characteristics related to PCOS. A euglycemic-hyperinsulinemic clamp was performed to assess insulin sensitivity. Circulating irisin concentrations were determined with ELISA. RESULTS: In our PCOS cohort, 65.8% of individuals were found to have hyperandrogenism. 83.8% had chronic oligoanovulation, and 80.3% of subjects showed polycystic ovaries. According to the diagnostic criteria of PCOS, 30.8% of PCOS subjects were diagnosed with the classic phenotype. In addition, 65.8% of PCOS women had insulin resistance. Serum irisin levels were significantly higher in PCOS women compared with healthy women. However, PCOS women with a normoandrogenic phenotype had similar circulating irisin levels as healthy women. PCOS women with the normoandrogenic phenotype had a low homeostasis model assessment of insulin resistance (HOMA-IR) and higher M-values than PCOS women with other phenotypes. Circulating irisin levels were associated with hyperandrogenism, but not with oligoanovulation or PCO morphology. CONCLUSIONS: Circulating irisin may allow physicians to establish which women merit screening by a biomarker for PCOS. PMID- 29785702 TI - A gastric feeding tube as a non-traumatic fistula probe during anal fistula repair. PMID- 29785703 TI - A Cross-Sectional Study Evaluating the Use of Free Clinics in Syracuse, NY: Patient Demographics and Barriers to Accessing Healthcare in Traditional Settings. AB - Free clinics provide healthcare to underserved patient populations, playing a critical role in the medical safety-net. Syracuse, New York has notable racial, socioeconomic, and educational disparities and is home to four free clinics. Little is known about these clinics' patient population. This study attempts to better define this population and the barriers they face accessing traditional care. We developed a 27-question survey investigating patient demographics, barriers to traditional healthcare, and experience at local free clinics. Our analysis included descriptive statistics, t-tests, one-way ANOVA and Chi square testing. Of 287 patients surveyed, 55% of patients were employed, 78% were uninsured, and 43% cited cost as their primary barrier to insurance. 29% rated their health as fair or poor. 21% had been to the Emergency Room (ER) in the past six months. 38% stated they would go to the ER if free clinics did not exist. Insurance coverage was unrelated to education or employment status (p = .52 and .81, respectively), but differed significantly between racial and ethnic groups (p < .007). Insured patients were more likely to have visited an ER in the past 6 months (p = .01), received preventive health services (p = .02), and seen a provider outside of the free clinic as compared to patients without insurance (p < .001). Free clinic patients represent a heterogeneous population with poor health indicators and several barriers to traditional care, especially cost. This information may aid public health agencies in developing policies to increase access to medical care and decrease morbidity and mortality among this population. PMID- 29785704 TI - The Role of Adolescent Victimization in Energy Drink Consumption: Monitoring the Future, 2010-2016. AB - Energy drinks have been linked to a number of deleterious health outcomes among youth. Even so, the underlying risk factors for energy drink consumption among youth are less frequently examined. The present study examines the link between adolescent victimization experiences (i.e., property and violent victimization) and energy drink consumption among a nationally representative sample of adolescents. We employed the seven most recent cohorts (2010-2016) from the Monitoring the Future (MTF) study. A multi-stage random sampling technique was used to acquire the U.S. sample. Youths reported the extent to which they consumed energy drinks. Additionally, three indicators of property victimization and four indicators of violent victimization were available in the data. The findings reveal a significant dose-response relationship between energy drink consumption and victimization. This relationship was especially pronounced among females. For instance, more than 52% of females with the highest count of various violent victimization experiences consumed energy drinks, which was three times the rate of females who had no previous violent victimization experiences. Practitioners who interact with adolescent victims may probe for energy drink usage in addition to other addictive substances such as alcohol, tobacco, and drugs. Additional scrutiny may also be in order in regulating the amount of caffeine and sugar allowed in these beverages. PMID- 29785705 TI - Association of GABAA Receptor Gene with Epilepsy Syndromes. AB - GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making alpha1, Upsilon2, and delta subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders. We explored the association of GABAA receptor gene mutation/SNPs in JME and LGS patients in Indian population. A total of 100 epilepsy syndrome patients (50 JME and 50 LGS) and 100 healthy control subjects were recruited and analyzed by AS-PCR and RFLP-PCR techniques. In our study, GABRA1 965 C > A mutation and 15 A > G polymorphism gene may play an important role in modulating the drug efficacy in LGS patients. The GABRA1 15 A > G polymorphism may also play an important role in the susceptibility of LGS and the inheritance of GG genotype of this polymorphism may provide an increased risk of development of LGS. The GABRG2 588 C > T polymorphism may decrease the duration of seizures in JME patients. The GABRD 659 G > A polymorphism may play an important role in the susceptibility of JME and LGS and this polymorphism may also increase the duration of postictal period in JME patients but may decrease the duration of seizure in LGS patients. PMID- 29785706 TI - Goal-Striving Stress Is Associated with Chronic Kidney Disease Among Participants in the Jackson Heart Study. AB - OBJECTIVE: Research that assesses the relationship between psychosocial factors and chronic kidney disease (CKD) among African Americans (AAs) is limited. Using the Jackson Heart Study (JHS) cohort data, we investigated the association of goal-striving stress (GSS)-the stress experienced from not reaching goals-with prevalent CKD among AAs. DESIGN: This was a cross-sectional analysis of JHS exam 1 data that assessed the relationship between GSS and CKD. SETTING AND PARTICIPANTS: We utilized a sample from the JHS (n = 4967), an AA sample of women and men, 35-84 years old from the Jackson, MS metro area. MAIN OUTCOME MEASURES: The baseline relationship between GSS levels (low, moderate, and high) and CKD (eGFR < 60 mL/min/1.73m2) was evaluated using a logistic regression model to estimate odds ratios (OR) on a 95% confidence interval (CI). The final model was adjusted for sex, age, socioeconomic status, health behaviors, risk factors, and total stress. RESULTS: After full adjustment, the odds of prevalent CKD increased by 52% (OR 1.52; 95% CI 1.04, 2.24) for those reporting high (versus low) GSS. CONCLUSIONS: Deficiencies between goal aspiration and achievement were associated with prevalent CKD. Potential interventions might consider the impact GSS contributes to prevalent CKD. PMID- 29785707 TI - Burden of Mental Illness and Non-communicable Diseases and Risk Factors for Mental Illness Among Refugees in Buffalo, NY, 2004-2014. AB - INTRODUCTION: Limited is known about mental illness and non-communicable diseases (NCDs) and their risk factors among refugees. These were studied using data collected from a refugee population in Buffalo, NY. METHODS: Longitudinal data collected on 1055 adults (> 18 years) at a large refugee health center in Buffalo, NY, during 2004-2014 were used. Main outcomes were hypertension, diabetes, tobacco use, obesity, overweight/obesity, and mental illness. Risk factors were assessed using multivariate regression models. RESULTS: Compared to those without mental illness, refugees with mental illness had higher rates of hypertension (16.9 vs 28.4%, P < 0.001), diabetes (8.4 vs 13.6%, P = 0.03), tobacco use (9.3 vs 18.3%, P < 0.001), obesity (13.0 vs 25.4%, P < 0.001), and overweight/obesity rates (45.0 vs 61.5%, P < 0.001). During 2004-2014, obesity rates increased among those with mental illness (25.4 to 36.7%, P < 0.001) and without mental illness (13.0 to 24.5%, P < 0.001). The overall mental illness prevalence among refugees was 16%, ranging from 6.9% among Asians to 43.9% among Cubans. Women were more likely to have mental illness (odds ratio = 2.45; 95% confidence interval [CI] = 1.68-3.58) than men. Refugees who lived longer in the USA were more likely to carry psychiatric diagnoses (OR = 1.12; 95% CI = 1.04 1.21). CONCLUSION: Mental illness rates varied considerably across various refugee groups. Rates of obesity and NCDs among refugees with mental illness were higher than among those without mental disorders. Gender, region of origin, and length of stay in the USA were associated with mental illness. Accurate and culturally sensitive screenings and assessments of mental illness are needed to reduce these health disparities. PMID- 29785708 TI - Prenatal predatory stress in a wild species of subterranean rodent: Do ecological stressors always have a negative effect on the offspring? AB - In pregnant females, a failed predatory event not only induces individual responses but also represents a significant change in the developmental environment of the offspring, which may lead to modifications in their phenotype that may persist at different stages of life. We evaluate whether prenatal exposure to predatory cues affects anxiety behavior, behavioral response to predator cues, stress response to immobilization, and immune response to sheep red blood cells (SRBC) and phytohemagglutinin (PHA) in juveniles of the subterranean rodent Ctenomys talarum. We found that prenatal predator stress (PPS) (1) increased juvenile anxiety-like behaviors and the appearance of antipredator behaviors, (2) did not affect the response of offspring to predatory stressors, and (3) did not influence the physiological response of juveniles to stressors (immobilization) nor the immunological responses to SRBC and PHA challenges. This work shows the influence of PPS on the development of behavioral responses in the offspring, whom displayed a state of anxiety and behavioral changes associated with decreased locomotor activity and avoidance behaviors. Thus, these individuals prenatally exposed to predatory cues show behavioral adaptations that may contribute to avoid predators in the adult life. PMID- 29785709 TI - Four-year follow-up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL). AB - Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR-MCL). We report the long-term outcome and safety profile of a single-centre, single arm, open-label, phase 2 study of RR-MCL treated with IR. Overall, the median follow-up time was 47 months (range 1-52 months), median duration on treatment was 16 months (range 1-53 months) and median number of treatment cycles was 17 (range 1-56). Twenty-nine patients (58%) achieved complete remission and of these, 12 patients continue on study. Thirty-eight patients discontinued treatment, 14 due to disease progression (2 transformed). Patients with blastoid morphology, high risk MCL International Prognostic Index score and high Ki67% had inferior survival. The commonest grade 1-2 toxicities were fatigue, diarrhoea, nausea, arthralgias and myalgias. None had long term toxicities. Median progression-free survival was 43 months. Eighteen patients (36%) died (14 deaths were MCL-related). The median overall survival has not been reached. Treatment with IR can provide durable remissions in a subset of patients with RR-MCL, especially those with low Ki67%. The possible benefit of adding other therapies in combination with IR in RR-MCL is under exploration. PMID- 29785711 TI - Illness as a Crisis of Meaning. AB - In Phenomenological Bioethics: Medical Technologies, Human Suffering, and the Meaning of Being Alive, the Swedish philosopher Fredrik Svenaeus aims to show how the continental tradition of phenomenology can enrich bioethical debates by adding important but often-ignored perspectives, namely, that of lived experience. Phenomenology focuses not on supposedly objective, scientifically validated facts, but on the "life world" of the individuals affected by a situation. Individuals' life worlds consist of their experience of their own lived bodies (or Leiber) and the meaning structures of their everyday worlds. A phenomenologically informed and oriented bioethics would seek to take those life worlds into account when considering what should be done in a particular ethically challenging situation. The fundamental insight that Svenaeus develops in his new book is that our illnesses are often, if not always, crises of meaning. PMID- 29785712 TI - There is moderate evidence that the process of service delivery for assistive technology relates to client satisfaction with the technology. PMID- 29785710 TI - Insomnia in Community-Living Persons with Advanced Age. AB - OBJECTIVE: To evaluate the epidemiology of insomnia, including demographic and clinical correlates, in older adults. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Yale Precipitating Events Project participants (N=379; mean age 84.3; 67.8% female; 11.9% African American). MEASUREMENTS: Insomnia Severity Index (ISI), with scores of 8 and higher indicating insomnia, which was further stratified according to ISI score as mild (8-14), moderate (15-21), or severe (22-28). Baseline characteristics included age, sex, race, education, smoking, obesity, medical conditions, depressive symptoms (Center for Epidemiologic Studies Depression score >=16), cognitive impairment (Mini-Mental State Examination score <24), restless legs syndrome (RLS), self-reported sleep disordered breathing (SDB), medications, and daytime sleepiness (Epworth Sleepiness Scale (ESS), range 0-24). RESULTS: Insomnia was established in 163 (43.0%) participants (average ISI score 12.3 (mild)). For the entire sample, average baseline characteristics were as follows: 30.1% did not complete high school, 5% were current smokers, 19.2% were obese, 28.2% had cardiovascular disease, 19.3% had chronic lung disease, 27.2% had depressive symptoms, 16.1% had cognitive impairment, 36.8% had RLS, and 3.4% had self-reported SDB; mean number of medications was 9.2, and mean ESS was 6.4. In multivariable regression models, only depressive symptoms (adjusted odds ratio (aOR)=8.34, 95% confidence interval (CI)=4.49, 15.47) and RLS (aOR=2.49, 95% CI=1.48, 4.21) were significantly associated with insomnia. CONCLUSION: In a sample of older adults with high medical burden and polypharmacy, insomnia was highly prevalent but unexpectedly mild and associated only with depressive symptoms and RLS. The discordance of high prevalence but mild severity of insomnia in the oldest adults highlights the need for diagnostic confirmation with objective measures of sleep disturbances, whereas the strong associations with depressive symptoms and RLS inform priorities in managing insomnia. PMID- 29785713 TI - Outcomes of oesophageal self-dilation for patients with refractory benign oesophageal strictures. AB - BACKGROUND: Current management of refractory benign oesophageal strictures with endoscopic dilations and stenting leads to resolution of dysphagia in only 30% of patients. Oesophageal self-dilation may be an alternative. AIM: To evaluate the efficacy and safety of oesophageal self-dilation at a tertiary referral centre. METHODS: We conducted a retrospective review of patients with refractory benign oesophageal strictures who participated in oesophageal self-dilation at Mayo Clinic (Rochester, MN, USA) between 2003 and 2017. Clinical data including stricture characteristics, Dakkak and Bennett Dysphagia Score, number and dates of endoscopies, and complications were collected. A two-tailed paired Student's t test was used to compare the measures of efficacy, with differences considered significant at a 5% probability level. RESULTS: We identified 52 patients with refractory strictures treated with self-dilation. The median number of endoscopic interventions was reduced from 9.5 (range 5-30) to 0 (range 0-3) within 12 months before and after self-dilation, respectively (P < 0.0001). A median intervention free interval of 417 days (IQR 256-756 days) was observed. The mean dysphagia score at baseline was 2.5 (95% CI 2.2-2.8) and 0.33 (95% CI 0.11-0.53) after self dilation. 23 of 27 (85%) patients who received enteral nutrition prior to self dilation had their feeding tubes removed. CONCLUSIONS: Oesophageal self-dilation is an effective way of maintaining oesophageal patency in refractory benign oesophageal strictures, with safety comparable to current standard of care. Prospective studies are needed to further validate the role of self-dilation in treatment of refractory benign oesophageal strictures. PMID- 29785714 TI - Lexical Learning May Contribute to Phonetic Learning in Infants: A Corpus Analysis of Maternal Spanish. AB - In their first year, infants begin to learn the speech sounds of their language. This process is typically modeled as an unsupervised clustering problem in which phonetically similar speech-sound tokens are grouped into phonetic categories by infants using their domain-general inference abilities. We argue here that maternal speech is too phonetically variable for this account to be plausible, and we provide phonetic evidence from Spanish showing that infant-directed Spanish vowels are more readily clustered over word types than over vowel tokens. The results suggest that infants' early adaptation to native-language phonetics depends on their word-form lexicon, implicating a much wider range of potential sources of influence on infants' developmental trajectories in language learning. PMID- 29785715 TI - Current advances in screening for bioactive components from medicinal plants by affinity ultrafiltration mass spectrometry. AB - INTRODUCTION: Medicinal plants have played an important role in maintaining human health for thousands of years. However, the interactions between the active components in medicinal plants and some certain biological targets during a disease are still unclear in most cases. OBJECTIVE: To conduct the high throughput screening for small active molecules that can interact with biological targets, which is of great theoretical significance and practical value. METHODOLOGY: The ultrafiltration mass spectrometry (UF-LC/MS) is a powerful bio analytical method by combining affinity ultrafiltration and liquid chromatography mass spectrometry (LC/MS), which could rapidly screen and identify small active molecules that bind to biological targets of interest at the same time. Compared with other analytical methods, affinity UF-LC/MS has the characteristics of fast, sensitive and high throughput, and is especially suitable for the complicated extracts of medicinal plants. RESULTS: In this review, the basic principle, characteristics and some most recent challenges in UF-LC/MS have been demonstrated. Meanwhile, the progress and applications of affinity UF-LC/MS in the discovery of the active components from natural medicinal plants and the interactions between small molecules and biological target proteins are also briefly summarised. In addition, the future directions for UF-LC/MS are also prospected. CONCLUSION: Affinity UF-LC/MS is a powerful tool in studies on the interactions between small active molecules and biological protein targets, especially in the high-throughput screening of active components from the natural medicinal plants. PMID- 29785717 TI - The place of abortion in the pregnancy decision-making process in young adult women in Catalonia, Spain. AB - Induced abortion is one option to control fertility in Spain. Young adult women (25-34 years old) show a different abortion pattern compared to women in other age groups, being less likely to seek abortions than younger women and having one of the lowest proportions of unintended pregnancies. We aimed to analyse the factors involved in the pregnancy decision-making process to better understand why young adult women seek abortions in Catalonia, Spain. In-depth semi structured interviews with 25 nulliparous pregnant young adult women and one focus group discussion with healthcare providers were conducted in 2008/2010. We found that inconsistent contraceptive use prior to an unintended pregnancy was due to ambivalence and weighing of priorities during sex. The quality of the relationship was paramount to the abortion decision whereas other reasons (financial/employment status, fulfilling aspirations, support networks) were less important. We conclude that the motivations for the abortion decision are interrelated and based on the current life stage of women and that there is pressure on young adult women in Spain to become mothers. Induced abortion is perceived as the last resort to postpone motherhood. Our findings reinforce the unequal societal burden placed on women to take responsibility for prevention of unintended pregnancy. PMID- 29785716 TI - Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.). AB - OBJECTIVE: To assess whether sonographic diagnosis of fetal head position before instrumental vaginal delivery can reduce the risk of failed vacuum extraction and improve delivery outcome. METHODS: Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.) is a randomized controlled trial of term (37 + 0 to 41 + 6 weeks' gestation) singleton pregnancies with cephalic presentation requiring instrumental delivery by vacuum extraction, which was conducted between April 2014 and June 2017 and involved 13 Italian maternity hospitals. Patients were randomized to assessment of fetal head position before attempted instrumental delivery by either vaginal examination (VE) alone or VE plus transabdominal sonography (TAS). Primary outcome was incidence of emergency Cesarean section due to failed vacuum extraction. A sample size of 653 women per group was planned to compare the primary outcome between the two groups. The sample size estimation was based on the hypothesis that the risk of failed vacuum delivery in the VE group would be 5% and that ultrasound assessment of fetal position prior to vacuum extraction would decrease this risk to 2%. RESULTS: On interim analysis, the trial was stopped for futility. During this period, 222 women were randomized and 221 were included in the final data analysis, of whom 132 (59.7%) were randomized to evaluation of fetal head position by VE only and 89 (40.3%) to assessment by VE plus TAS prior to vacuum extraction. No significant differences were observed between the two groups with respect to incidence of emergency Cesarean section due to failed instrumental delivery and other maternal and fetal outcomes. Women randomized to assessment by VE plus TAS showed higher incidence of non-occiput anterior position of the fetal head at randomization and lower incidence of incorrect diagnosis of occiput position compared with women undergoing assessment by VE alone. A higher rate of episiotomy was noted in the women undergoing both VE and TAS compared with those in the VE-only group. CONCLUSIONS: Our prematurely discontinued randomized controlled trial did not demonstrate any benefit in terms of reduced risk of failed instrumental delivery or maternal and fetal morbidity in women undergoing sonographic assessment of fetal head position prior to vacuum extraction. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd. PMID- 29785719 TI - Children's experiences and expectations of kidney transplantation: A qualitative interview study. AB - RATIONALE AND OBJECTIVE: Kidney transplantation offers improved quality of life and life expectancy compared with dialysis for children. This study aims to understand the experiences and expectations of children during the kidney transplantation process to inform clinical care. STUDY DESIGN: Face-to-face, semi structured interviews. SETTING AND PARTICIPANTS: We interviewed 13 children and adolescents aged between 7 and 17 years old in New Zealand who had received a kidney transplantation. ANALYTICAL APPROACH: We conceptualised the findings using thematic analysis with inductive coding. RESULTS: We identified three major themes: transplant as the goal (the only real treatment and escaping dialysis); dealing with negative emotions (coping with anxiety and fear, guilt for siblings and burden of parent as donor); and enhancing understanding and knowledge (individualised education and reassurance from peer support). LIMITATIONS: Study conducted in New Zealand therefore, the transferability of findings to other populations is unclear. CONCLUSIONS: Children and adolescents view transplantation as freedom from dialysis and return to a more normal life. Children focus on the positive aspects of transplantation to reduce anxiety and be reassured in the face of uncertainty. Complex emotions arise when thinking about their donor. Children recognise transplantation is not a return to full health and actively seek out ways to self-manage their care, while remaining anxious about their future. This article is protected by copyright. All rights reserved. PMID- 29785718 TI - Associations between the smoking-relatedness of a cancer type, cessation attitudes and beliefs, and future abstinence among recent quitters. AB - OBJECTIVE: Smoking after a diagnosis of cancer can negatively impact treatment outcomes and quality of life. It is important that patients quit smoking and remain abstinent regardless of cancer type. Some cancer types (eg, lung) have stronger links to smoking as a cause than do others (eg, colorectal). The aims of this study were to (1) assess associations between smoking-relatedness of the cancer type with beliefs and attitudes concerning smoking abstinence (eg, confidence, self-efficacy), and (2) assess these variables as predictors of future abstinence. METHODS: In this secondary analysis, cancer patients (N = 357) who quit smoking within the previous 90 days were assigned a code of 3, 2, or 1 according to the cancer type's level of smoking-relatedness: Very related (n = 134, thoracic and head and neck), Somewhat related (n = 93, acute myeloid leukemia, bladder, cervix, colorectal, esophageal, kidney, liver, pancreas, and stomach), and Unlikely related (n = 137, all other cancer types). RESULTS: Smoking-relatedness was positively associated with plan to stay smoke-free, maximum confidence in being smoke-free in 6 months, higher abstinence self efficacy, and lower expected difficulty in staying smoke-free. Each of the 4 beliefs and attitude variables predicted abstinence 2 months later. Smoking relatedness also predicted abstinence in a univariate model, but not in a multivariable model with the belief and attitude variables. Using backwards stepwise procedures, the final model included plan to stay smoke-free, confidence in being smoke-free, and abstinence self-efficacy. CONCLUSION: These results are consistent with our conceptualization of cessation motivation differing by smoking-relatedness of the cancer type and predicting future abstinence. PMID- 29785720 TI - Mobility scores as a predictor of length of stay in general surgery: a prospective cohort study. AB - BACKGROUND: Post-operative length of stay (LOS) is an increasingly important clinical indicator in general surgery. Despite this, no tool has been validated to predict LOS or readiness for discharge in general surgical patients. The de Morton Mobility Index (DEMMI) is a functional mobility assessment tool that has been validated in rehabilitation patient populations. In this prospective cohort study, we aimed to identify if trends in DEMMI scores were associated with discharge within 1 week and overall LOS in general surgical patients. METHODS: A total of 161 patients who underwent elective gastrointestinal resections were included. DEMMI scores were performed preoperatively, on days 1, 2, 3 and 30 post operative. Statistical analysis was performed to identify any association between DEMMI scores and discharge within 1 week and LOS. RESULTS: Functional recovery (measured by achieving 80% of baseline DEMMI score by post-operative day 1) was significantly associated with discharge within 1 week. Presence of a stoma was associated with longer LOS. The area under the receiver operating characteristic curve using functional recovery on post-operative day 1 as a predictor of discharge within 1 week is 0.772. CONCLUSION: The DEMMI score is a fast, easy and useful tool to, on post-operative day 1, predict discharge within 1 week. The utility of this is to act as an anticipatory trigger for more proactive and efficient discharge planning in the early post-operative period, and there is potential to use the DEMMI as a comparator in clinical trials to assess functional recovery. PMID- 29785721 TI - Heeding humanity in an age of electronic health records: Heidegger, Levinas, and Healthcare. AB - The American Recovery and Reinvestment Act of 2009 (ARRA) required healthcare providers in the United States to adopt and demonstrate meaningful use of electronic health records (EHRs) by January 1, 2014. In many ways, EHRs mark a notable improvement over paper medical records as they are more easily accessible and allow for electronic searching and sharing of medical history. However, as EHRs have become mandated by ARRA, many nurses now rely upon computers far more heavily during nurse-patient interactions, thereby decreasing the level of direct interpersonal communication between the two. There is evidence that eye contact between nurses and patients positively affects patient satisfaction. Above and beyond the issue of patient satisfaction is the more basic ethical issue of respecting the patient as a person. The author argues that the templates used in electronic health systems have the possibility of eroding the respect for humanity that is the hallmark of nurse-patient relationships, as signalled by the American Nurses Association's first principle in their Code of Ethics. Using concepts from philosophers Martin Heidegger and Emmanuel Levinas, the author provides guidance as to what an ethical interaction between nurse and patient should look like in an age of EHRs. PMID- 29785724 TI - Social Transmission of False Memory in Small Groups and Large Networks. AB - Sharing information and memories is a key feature of social interactions, making social contexts important for developing and transmitting accurate memories and also false memories. False memory transmission can have wide-ranging effects, including shaping personal memories of individuals as well as collective memories of a network of people. This paper reviews a collection of key findings and explanations in cognitive research on the transmission of false memories in small groups. It also reviews the emerging experimental work on larger networks and collective false memories. Given the reconstructive nature of memory, the abundance of misinformation in everyday life, and the variety of social structures in which people interact, an understanding of transmission of false memories has both scientific and societal implications. PMID- 29785723 TI - Decreased E-Cadherin in MCF7 Human Breast Cancer Cells Forming Multicellular Spheroids Exposed to Simulated Microgravity. AB - MCF7 human breast cancer cells were cultured under normal gravity (1 g) and on a random positioning machine (RPM) preventing sedimentation. After 2 weeks, adherent 1 g-control and adherent RPM cells (AD) as well as multicellular spheroids (MCS) were harvested. AD and MCS had been exposed to the RPM in the same culture flask. In a subsequent proteome analysis, the majority of the proteins detected showed similar label-free quantification (LFQ) scores in each of the respective subpopulations, but in both AD or MCS cultures, proteins were also found whose LFQs deviated at least twofold from their counterparts in the 1 g-control cells. They included the cell junction protein E-cadherin, which was diminished in MCS cells, where proteins of the E-cadherin autodegradation pathway were enhanced and c-Src (proto-oncogene tyrosine-protein kinase c-Src) was detected. Spheroid formation was prevented by inhibition of c-Src but promoted by antibodies blocking E-cadherin activity. An interaction analysis of the detected proteins that are involved in forming and regulating junctions or adhesion complexes and in E-cadherin autodegradation indicated connections between the two protein groups. This suggests that the balance of proteins that up- or downregulate E-cadherin mediates the tendency of MCF7 cells to form MCS during RPM exposure. PMID- 29785722 TI - Electrostatic recognition in substrate binding to serine proteases. AB - Serine proteases of the Chymotrypsin family are structurally very similar but have very different substrate preferences. This study investigates a set of 9 different proteases of this family comprising proteases that prefer substrates containing positively charged amino acids, negatively charged amino acids, and uncharged amino acids with varying degree of specificity. Here, we show that differences in electrostatic substrate preferences can be predicted reliably by electrostatic molecular interaction fields employing customized GRID probes. Thus, we are able to directly link protease structures to their electrostatic substrate preferences. Additionally, we present a new metric that measures similarities in substrate preferences focusing only on electrostatics. It efficiently compares these electrostatic substrate preferences between different proteases. This new metric can be interpreted as the electrostatic part of our previously developed substrate similarity metric. Consequently, we suggest, that substrate recognition in terms of electrostatics and shape complementarity are rather orthogonal aspects of substrate recognition. This is in line with a 2-step mechanism of protein-protein recognition suggested in the literature. PMID- 29785725 TI - Density scaling of phantom materials for a 3D dose verification system. AB - In this study, the optimum density scaling factors of phantom materials for a commercially available three-dimensional (3D) dose verification system (Delta4) were investigated in order to improve the accuracy of the calculated dose distributions in the phantom materials. At field sizes of 10 * 10 and 5 * 5 cm2 with the same geometry, tissue-phantom ratios (TPRs) in water, polymethyl methacrylate (PMMA), and Plastic Water Diagnostic Therapy (PWDT) were measured, and TPRs in various density scaling factors of water were calculated by Monte Carlo simulation, Adaptive Convolve (AdC, Pinnacle3 ), Collapsed Cone Convolution (CCC, RayStation), and AcurosXB (AXB, Eclipse). Effective linear attenuation coefficients (MUeff ) were obtained from the TPRs. The ratios of MUeff in phantom and water ((MUeff )pl,water ) were compared between the measurements and calculations. For each phantom material, the density scaling factor proposed in this study (DSF) was set to be the value providing a match between the calculated and measured (MUeff )pl,water . The optimum density scaling factor was verified through the comparison of the dose distributions measured by Delta4 and calculated with three different density scaling factors: the nominal physical density (PD), nominal relative electron density (ED), and DSF. Three plans were used for the verifications: a static field of 10 * 10 cm2 and two intensity modulated radiation therapy (IMRT) treatment plans. DSF were determined to be 1.13 for PMMA and 0.98 for PWDT. DSF for PMMA showed good agreement for AdC and CCC with 6 MV x ray, and AdC for 10 MV x ray. DSF for PWDT showed good agreement regardless of the dose calculation algorithms and x-ray energy. DSF can be considered one of the references for the density scaling factor of Delta4 phantom materials and may help improve the accuracy of the IMRT dose verification using Delta4. PMID- 29785726 TI - T2-hypointense rim of breast mass lesions on magnetic resonance images: Radiologic-pathologic correlation. AB - We investigated the radiologic-pathologic correlation of a strong hypointense rim on T2-weighted images (T2-hypo-rim) surrounding breast mass lesions and evaluated its clinical significance. We retrospectively reviewed 3503 consecutive breast magnetic resonance imaging (MRI) examinations. The T2-hypo-rim was defined as a border of strong hypointensity compared with the fat signal on fat-suppressed T2 weighted images. Detected lesions with T2-hypo-rim were classified as a solid or cystic mass with MRI and correlated with histopathologic findings. Sixty-two masses (2%; 34 solid, 28 cystic) with T2-hypo-rim were detected [44 breast cancers, 18 benign lesions, including 15 (24%) papillary tumors]. Patients with cancer were significantly older than those with benign lesions (P = .002). Breast cancers were significantly larger than benign masses (P = .023). In 49 of 62 lesions (24 solid and 16 cystic cancers; three solid and six cystic benign masses), the rims were accurately correlated with the histopathologic findings. All malignant and benign cystic masses exhibited hemosiderin deposits in the cyst walls. However, 22 of 24 solid cancers and no solid benign masses exhibited hemosiderin at the tumor periphery (92% and 0%, respectively, P < .001). In addition, a thick fibrous capsule was present in nine (38%) of 24 solid cancers and none of the solid benign lesions. Strong T2-hypo-rims mostly correlated with hemosiderin deposits and/or sometimes fibrous capsules. Although the rims could not distinguish malignant from benign cystic lesions, they indicated malignancy in solid mass lesions on MRI. Additionally, the rims often indicated papillary tumors. PMID- 29785728 TI - Ultrafast capillary electrophoresis method for the simultaneous determination of ammonium and diphenhydramine in pharmaceutical samples. AB - Ammonium and diphenhydramine are active ingredients commonly found in the same pharmaceutical preparations. We report, for the first time, a sub-minute method for the simultaneous determination of ammonium and diphenhydramine. The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection. Both analytes can be quantified in a single run (~80 injections/h) using 30 mmol/L 2-(N-morpholino)ethanesulfonic acid and 15 mmol/L lithium hydroxide (pH 6.0) as background electrolyte. The separation by capillary electrophoresis was achieved on a fused-silica capillary (50 cm total length, 10 cm effective length, and 50 MUm inside diameter). The limits of detection were 0.04 and 0.02 mmol/L for ammonium and diphenhydramine, respectively. The proposed method also provided adequate recovery values for spiked samples (100-106 and 97 104% for ammonium and diphenhydramine, respectively). The results obtained with the new capillary electrophoresis method were compared with those of the high performance liquid chromatography method for diphenhydramine and the Kjeldahl method for ammonium and no statistically significant differences were found (95% confidence level). PMID- 29785727 TI - Body Composition Profiling in the UK Biobank Imaging Study. AB - OBJECTIVE: This study aimed to investigate the value of imaging-based multivariable body composition profiling by describing its association with coronary heart disease (CHD), type 2 diabetes (T2D), and metabolic health on individual and population levels. METHODS: The first 6,021 participants scanned by UK Biobank were included. Body composition profiles (BCPs) were calculated, including abdominal subcutaneous adipose tissue, visceral adipose tissue (VAT), thigh muscle volume, liver fat, and muscle fat infiltration (MFI), determined using magnetic resonance imaging. Associations between BCP and metabolic status were investigated using matching procedures and multivariable statistical modeling. RESULTS: Matched control analysis showed that higher VAT and MFI were associated with CHD and T2D (P < 0.001). Higher liver fat was associated with T2D (P < 0.001) and lower liver fat with CHD (P < 0.05), matching on VAT. Multivariable modeling showed that lower VAT and MFI were associated with metabolic health (P < 0.001), and liver fat was nonsignificant. Associations remained significant adjusting for sex, age, BMI, alcohol, smoking, and physical activity. CONCLUSIONS: Body composition profiling enabled an intuitive visualization of body composition and showed the complexity of associations between fat distribution and metabolic status, stressing the importance of a multivariable approach. Different diseases were linked to different BCPs, which could not be described by a single fat compartment alone. PMID- 29785729 TI - TG-51 reference dosimetry for the HalcyonTM: A clinical experience. AB - HalcyonTM is a single-energy (6 MV-FFF), bore-enclosed linear accelerator. Patient setup is performed by first aligning to external lasers mounted to the front of the bore, and then loading to isocenter through pre-defined couch shifts. There is no light field, optical distance indicator or front pointer mechanism, so positioning is verified through MV imaging with kV imaging scheduled to become available in the future. TG-51 reference dosimetry was successfully performed for HalcyonTM in this imaging-based setup paradigm. The beam quality conversion factor, kQ , was determined by measuring %dd(10)x three ways: (a) using a Farmer chamber with lead filtering, (b) using a Farmer chamber without lead filtering, and (c) using a PinPoint chamber without lead filtering. Values of kQ were determined to be 0.995, 0.996, and 0.996 by each measurement technique, respectively. HalcyonTM's 6 MV-FFF beam was found to be broader than other FFF beams produced by Varian accelerators, and profile measurements at dmax showed the beam to vary less than 0.5% over the dimensions of our Farmer chamber's active volume. Reference dosimetry can be performed for the HalcyonTM accelerator simply, without specialized equipment or lead filtering with minimal dosimetric impact. This simplicity will prove advantageous in clinics with limited resources or physics support. PMID- 29785730 TI - Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa. AB - Historically, Australia was considered free of rabies and rabieslike viruses. Thus, the identification of Australian bat lyssavirus (ABLV) in 1996 in a debilitated bat found by a member of the public precipitated both public health consternation and a revision of lyssavirus taxonomy. Subsequent observational studies sought to elaborate the occurrence and frequency of ABLV infection in Australian bats. This paper describes the taxonomic diversity of bat species showing evidence of ABLV infection to better inform public health considerations. Blood and/or brain samples were collected from two cohorts of bats (wild-caught and diagnostic submissions) from four Australian states or territories between April 1996 and October 2002. Fresh brain impression smears were tested for ABLV antigen using fluorescein-labelled anti-rabies monoclonal globulin (CENTOCOR) in a direct fluorescent antibody test; sera were tested for the presence of neutralising antibodies using a rapid fluorescent focus inhibition test. A total of 3,217 samples from 2,633 bats were collected and screened: brain samples from 1,461 wild-caught bats and 1,086 submitted bats from at least 16 genera and seven families, and blood samples from 656 wild-caught bats and 14 submitted bats from 14 genera and seven families. Evidence of ABLV infection was found in five of the six families of bats occurring in Australia, and in three of the four Australian states/territories surveyed, supporting the historic presence of the virus in Australia. While the infection prevalence in the wild-caught cohort is evidently low, the significantly higher infection prevalence in rescued bats in urban settings represents a clear and present public health significance because of the higher risk of human exposure. PMID- 29785731 TI - Semantic future thinking and executive functions at age 4: The moderating role of frontal brain electrical activity. AB - Previous studies provide conflicting results regarding the relation between future thinking and executive functioning during early childhood. Furthermore, little is known of the neural mechanisms involved in future thinking during early childhood. We examined the moderating role of frontal electroencephalogram (EEG) activity on the relation between executive functioning and semantic future thinking performance in a sample of 4-year-old children. Our results suggest that frontal EEG moderates the relation between executive functioning and semantic future thinking performance, but only for medium to high levels of frontal EEG power values. These results provide emerging evidence regarding the role of both executive functioning and frontal brain electrical activity on semantic future thinking in 4-year-olds. PMID- 29785732 TI - The Mental Representation of Human Action. AB - Various theories of moral cognition posit that moral intuitions can be understood as the output of a computational process performed over structured mental representations of human action. We propose that action plan diagrams-"act trees" can be a useful tool for theorists to succinctly and clearly present their hypotheses about the information contained in these representations. We then develop a methodology for using a series of linguistic probes to test the theories embodied in the act trees. In Study 1, we validate the method by testing a specific hypothesis (diagrammed by act trees) about how subjects are representing two classic moral dilemmas and finding that the data support the hypothesis. In Studies 2-4, we explore possible explanations for discrete and surprising findings that our hypothesis did not predict. In Study 5, we apply the method to a less well-studied case and show how new experiments generated by our method can be used to settle debates about how actions are mentally represented. In Study 6, we argue that our method captures the mental representation of human action better than an alternative approach. A brief conclusion suggests that act trees can be profitably used in various fields interested in complex representations of human action, including law, philosophy, psychology, linguistics, neuroscience, computer science, robotics, and artificial intelligence. PMID- 29785733 TI - Left Ventricular Strain Analysis Using Cardiac MRI in Patients Undergoing In centre Nocturnal Hemodialysis. AB - AIM: Intensified haemodialysis is associated with regression of left ventricular (LV) mass. Compared to LV ejection fraction, LV strain allows more direct assessment of LV function. We sought to assess the impact of in-centre nocturnal haemodialysis (INHD) on global LV strain (radial, circumferential, and longitudinal) and torsion by cardiac MRI (CMR). METHODS: In this prospective, 2 centre cohort study, 37 participants on conventional haemodialysis (CHD, 3-4 hours/session for 3 sessions/week) converted to INHD (7-8 hours/session for 3 sessions/week) and 30 participants continued CHD. Participants underwent CMR using a standardized protocol and had biomarker measurements at baseline and 52 weeks. RESULTS: Among the 55 participants (mean age 55; 40% women) with complete CMR data, those who converted to INHD had a significant improvement in their global circumferential strain (GCS, p=0.025), while those continuing CHD did not have any significant changes in LV strain. When the 2 groups were compared, there was significant improvement in torsion. LV strains were significantly correlated with each other, but not with troponin I, C-reactive protein, or brain natriuretic protein (NT-proBNP), except for global longitudinal strain (GLS) with troponin I (p=0.001) and NT-proBNP (p=0.038). CONCLUSION: Conversion to INHD was associated with significant improvement in GCS over one year of study, although comparisons with the CHD group were not significant. There was also a significant decrease in torsion in the INHD group compared with CHD. Improvement in LV regional function would support the notion that INHD has favourable effects on both LV structure and function. This article is protected by copyright. All rights reserved. PMID- 29785735 TI - Pyelo-choledochal fistulation on intraoperative cholangiogram. PMID- 29785734 TI - Biallelic BIRC3 inactivation in chronic lymphocytic leukaemia patients with 11q deletion identifies a subgroup with very aggressive disease. PMID- 29785736 TI - New connections between circadian rhythms, photosynthesis, and environmental adaptation. AB - This article comments on: Circadian rhythms are associated with variation in photosystem II function and photoprotective mechanisms. PMID- 29785737 TI - Clinical Proteomics: Closing the Gap from Discovery to Implementation. AB - Clinical proteomics, the application of proteome analysis to serve a clinical purpose, represents a major field in the area of proteome research. Over 1000 manuscripts on this topic are published each year, with numbers continuously increasing. However, the anticipated outcome, the transformation of the reported findings into improvements in patient management, is not immediately evident. In this article, the value and validity of selected clinical proteomics findings are investigated, and it is assessed how far implementation has progressed. A main conclusion from this assessment is that to achieve implementation, well-powered clinical studies are required in the appropriate population, addressing a specific clinical need and with a clear context-of-use. Efforts toward implementation, to be feasible, must be supported by the key players in science: publishers and funders. The authors propose a change on objectives, from additional discovery studies toward studies aiming at validation of the plethora of potential biomarkers that have been described, to demonstrate practical value of clinical proteomics. All elements required, potential biomarkers, technologies, and bio-banked samples are available (based on today's literature), hence a change in focus from discovery toward validation and application is not only urgently necessary, but also possible based on resources available today. PMID- 29785738 TI - Mass spectrometry for characterization of homologous piperidine alkaloids and their activity as acetylcholinesterase inhibitors. AB - RATIONALE: Piperidine alkaloids from Senna spectabilis constitute a rare class of natural products with several biological activities. However, the absence of chromophores makes their structural elucidation by conventional methods a great challenge. In this context, mass spectrometry emerges as a powerful tool for metabolomics studies. METHODS: The piperidine alkaloids (-)-cassine and (-) spectaline and the semisynthetic derivatives (-)-3-O-acetylcassine and (-)-3-O acetylspectaline were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the positive mode and electron ionization mass spectrometry (EI-MS). ESI fragmentation studies were performed with a quadrupole time-of-flight instrument; N2 was used as collision gas. The acetylcholinesterase inhibitory activity of the investigated compounds was evaluated by bioautography and microplate screening assays. RESULTS: ESI-MS/MS and EI-MS provided valuable and complementary information about the structure of the piperidine compounds. Collision-induced dissociation experiments (MS/MS) revealed that neutral elimination of water or acetic acid is the major fragmentation pathway, which agrees with the stereochemistry proposed for (-)-cassine and (-)-spectaline and the semisynthetic derivatives (-)-3-O-acetylcassine and (-)-3-O-acetylspectaline. CONCLUSIONS: The ESI-MS/MS and EI-MS studies allowed us to propose fragmentation mechanisms for piperidine alkaloids and derivatives. Therefore, mass spectrometry is an important tool for characterizing the structure of these compounds and for supporting further metabolomics studies. PMID- 29785739 TI - In vitro formation of the Merkel cell-neurite complex in embryonic mouse whiskers using organotypic co-cultures. AB - A Merkel cell-neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch-sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell neurite complex, and therefore it is intriguing how the structure is formed. However, observing the dynamic process of the formation of a Merkel cell-neurite complex in whiskers during embryonic development is still difficult. In this study, we tried to develop an organotypic co-culture method of a whisker pad and a trigeminal ganglion explant to form the Merkel cell-neurite complex in vitro. We initially developed two distinct culture methods of a single whisker row and a trigeminal ganglion explant, and then combined them. By dissecting and cultivating a single row from a whisker pad, the morphogenesis of whisker follicles could be observed under a microscope. After the co-cultivation of the whisker row with a trigeminal ganglion explant, a Merkel cell-neurite complex composed of Merkel cells, which were positive for both cytokeratin 8 and SOX2, Neurofilament-H-positive trigeminal nerve fibers and Schwann cells expressing Nestin, SOX2 and SOX10 was observed via immunohistochemical analyses. These results suggest that the process for the formation of a Merkel cell-neurite complex can be observed under a microscope using our organotypic co-culture method. PMID- 29785740 TI - Expression levels of breast cancer-related GAS5 and LSINCT5 lncRNAs in cancer free breast tissue: Molecular associations with age at menarche and obesity. AB - Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI >= 25) subgroup than that in the normal BMI (BMI < 25) subgroup (GAS5 P = .019, LSINCT5 P = .036). Moreover, the expression level of GAS5 was negatively correlated with BMI (r: -.170, P: .041). The expression level of GAS5 was higher in women with late menarche (>13 years) than that with early menarche (<=13 years; P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women. PMID- 29785741 TI - Intergroup Contact Attitudes Across Peer Networks in School: Selection, Influence, and Implications for Cross-Group Friendships. AB - This study offers new insights into the power of peer networks for shaping intergroup relations in a diverse school. Data were drawn from a longitudinal study of sixth-eighth graders (N = 524; MageT1 = 11.87; 48% girls; 9% Asian American/Pacific Islander, 28% African American, 13% Latino, 1% Native American, 31% White, 5% Other, and 11% Multiracial) in the Midwestern United States. Students with more positive intergroup contact attitudes (ICA) were most likely to be friends with similarly minded students. Students with more positive ICA were less likely to select friends of the same race/ethnicity than those with less positive ICA. Finally, students' ICA became more similar to their friends' ICA over time. Results implicate school-level norms and contagion in students' ICA. PMID- 29785742 TI - Synthesis and Characterization of a New Bifunctionalized, Fluorescent, and Amphiphilic Molecule for Recruiting SH-Containing Molecules to Membranes. AB - This study describes the synthesis and characterization of an amphiphilic construct intended to recruit SH-containing molecules to membranes. The construct consists of 1) an aliphatic chain to enable anchoring within membranes, 2) a maleimide moiety to react with the sulfhydryl group of a soluble (bio)molecule, and 3) a fluorescence moiety to allow the construct to be followed by fluorescence spectroscopy and microscopy. It is shown that the construct can be incorporated into preformed membranes, thus allowing application of the approach with biological membranes. The close proximity between the fluorophore and the maleimide moiety within the construct causes fluorescence quenching. This allows monitoring of the reaction with SH-containing molecules by measurement of increases in fluorescence intensity and lifetime. Notably, the construct distributes into laterally ordered membrane domains of lipid vesicles, which is probably triggered by the length of its membrane anchor. The advantages of the new construct can be employed for several biological, biotechnological, and medicinal applications. PMID- 29785743 TI - Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii. AB - Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as 'Chuanwu' and 'Fuzi', respectively. Four new C19 -diterpenoid alkaloids, carmichasines A - D (1 - 4), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds (5 - 16). Their structures were elucidated via spectroscopic analyses, including HR-ESI-MS, IR, and NMR. Carmichasine A (1) is the first natural C19 -diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C19 -category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF-7, HCT116, A549, and 786-0, and none of them showed considerable cytotoxic activity. PMID- 29785744 TI - Fumonisin B1 actuates oxidative stress-associated colonic damage via apoptosis and autophagy activation in murine model. AB - In the present study, we investigated the cytotoxic mechanism of Fumonisin B1 (FB1) in mice colonic region in a time course manner. Herein, after consecutive 4 days of exposure to FBI (2.5 mg/kg body weight), we observed disintegration of mice colon, as evidenced by histopathological analysis. FB1 significantly increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities in serum and plasma, decreased ceramide level, increased sphinganine level, and increased lipid peroxidase level along with the breakdown of the antioxidant system. Further, FB1-induced ER stress caused apoptosis and autophagy activation in mice colon, evidenced by increased expression of IRE1 alpha, p-JNK, Casp3, and LC3I/II. In addition, we also noticed a reduced protein kinase C expression in mice colon exposed to FB1, suggesting its role in ER stress-induced cell death. Taken together, study suggests both physiologically and biochemically, FB1 toxicity to mice colon induced by oxidative stress associated apoptosis and autophagy activation. PMID- 29785745 TI - Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding. AB - AIM: To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding. METHODS: A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non-PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan-Meier approach and the log rank test. RESULTS: A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non-PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2-year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non-PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups. CONCLUSION: The use of PPI in bedridden tube fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non-significant lower incidence of gastrointestinal bleeding than the non-PPI group. Geriatr Gerontol Int 2018; 18: 1215-1218. PMID- 29785746 TI - Systematic In-Depth Proteomic Analysis of Mitochondria-Associated Endoplasmic Reticulum Membranes in Mouse and Human Testes. AB - Mitochondria-associated endoplasmic reticulum membranes (MAMs) regulate important cellular functions including calcium signaling, bioenergetics, and apoptosis during neurodevelopment and carcinogenesis, but its function in male reproduction and spermatogenesis remains enigmatic because the field lacks a complete understanding of the proteome within testis MAMs. To better understand the biological processes and molecular functions of MAM in testes, a global mass spectrometry-based proteomic evaluation of MAM proteins from human and mouse testes are reported here, respectively. The evaluation and analysis showed that the components of MAM were highly conserved not only between different species (human and mouse) but also between different tissues (testes and brains). Bioinformatics interrogation of these MAM protein catalogues uncovered that 815 new potential linkages specifically existed in mouse testes compared with mouse brains. In addition, a comparative analysis showed that 1347 proteins (account for ~96.56%) were highly conservatively expressed in both human and mouse testis MAMs. Furthermore, functional analysis revealed that testis-specific MAM proteins were related to spermatogenesis, male gamete generation, as well as sexual reproduction. The data identified, for the first time, numerous MAM proteins in mouse and human testes, which provide a possibility to define the relationship between testis MAM proteins and reproductive diseases. PMID- 29785747 TI - Functional and clinical outcomes of patients aged younger and older than 85 years after rehabilitation post-hip fracture surgery in a co-managed orthogeriatric unit. AB - AIM: Literature investigating rehabilitation outcomes after hip surgery among individuals aged >=85 years is sparse. We compared the characteristics and outcomes of patients aged under and over 85 years, and assessed factors potentially associated with rehabilitation success as described by the Barthel Index (BI). METHODS: From 2011 to 2014, we prospectively enrolled 328 patients (n = 152 aged <85 years, n = 176 aged >=85 years) admitted to an orthogeriatric unit (Sondrio, Italy) with a diagnosis of hip fracture requiring surgical treatment. We excluded patients who were being treated conservatively. Outcomes included absolute functional gain (AFG; BI at discharge - BI on admission), rehabilitation effectiveness index (AFG / length of stay) and postoperative complications. RESULTS: Older patients were more functionally (mean BI on admission: 11.7 +/- 9.6 vs 16.4 +/- 12.2, P < 0.001) and cognitively impaired than their younger counterparts (34.1% vs 18.4%, P < 0.001). Surgery time (1.9 +/- 1.2 vs 2.3 +/-1.3 days, P = 0.008) and length of stay were shorter for older patients (5.7 +/- 2.1 vs 6.6 +/- 2.4 days, P < 0.001). There were no differences in terms of complications. Patients aged <85 years showed better functional outcomes (BI, AFG, REI) at discharge than patients aged >=85 years (mean AFG: 38.2 +/- 24.2 vs 26.1 +/- 22.0, P < 0.001). BI on admission (OR 1.05, 95% CI 1.02-1.08) and cognitive impairment (OR 0.58, 95% CI 0.34-0.98) were independently associated with rehabilitation outcomes, regardless of chronological age. CONCLUSIONS: Both groups (aged <85 and >=85 years) showed a significant functional improvement at discharge. Older patients show a residual ability to recover after surgery. A high rehabilitation efficiency - regardless of age - should be pursued even for the oldest old patients experiencing hip fracture. Geriatr Gerontol Int 2018; 18: 1194-1199. PMID- 29785748 TI - The relation of respiratory sinus arrhythmia to later shyness: Moderation by neighborhood quality. AB - The purpose of the study was to predict young children's shyness from both internal/biological (i.e., resting respiratory sinus arrhythmia; RSA) and external (i.e., neighborhood quality) factors. Participants were 180 children at 42 (Time 1; T1), 72 (T2), and 84 (T3) months of age. RSA data were obtained at T1 during a neutral film in the laboratory. Mothers reported perceived neighborhood quality at T2 and children's dispositional shyness at T1 and T3. Path analyses indicated that resting RSA interacted with neighborhood quality to predict T3 shyness, even after controlling for earlier family income and T1 shyness. Specifically, high levels of resting RSA predicted low levels of shyness in the context of high neighborhood quality. When neighborhood quality was low, resting RSA was positively related to later shyness. These findings indicate that children's shyness is predicted by more than biological processes and that consideration of the broader context is critical to understanding children's social behavior. PMID- 29785751 TI - The American Society for Preventive Cardiology. PMID- 29785749 TI - Cardiac vagal regulation in infancy predicts executive function and social competence in preschool: Indirect effects through language. AB - Parasympathetic nervous system functioning in infancy may serve a foundational role in the development of cognitive and socioemotional skills (Calkins, 2007). In this study (N = 297), we investigated the potential indirect effects of cardiac vagal regulation in infancy on children's executive functioning and social competence in preschool via expressive and receptive language in toddlerhood. Vagal regulation was assessed at 10 months during two attention conditions (social, nonsocial) via task-related changes in respiratory sinus arrhythmia (RSA). A path analysis revealed that decreased RSA from baseline in the nonsocial condition and increased RSA in the social condition were related to larger vocabularies in toddlerhood. Additionally, children's vocabulary sizes were positively related to their executive function and social competence in preschool. Indirect effects from vagal regulation in both contexts to both 4-year outcomes were significant, suggesting that early advances in language may represent a mechanism through which biological functioning in infancy impacts social and cognitive functioning in childhood. PMID- 29785750 TI - Cellulose membrane modified with polypyrrole as an extraction device for the determination of emerging contaminants in river water with gas chromatography mass spectrometry. AB - In this study, a simple, efficient, and reusable device based on cellulose membranes modified with polypyrrole was developed to extract 14 emerging contaminants from aqueous matrices. For chemical polymerization, a low-cost cellulose membrane was immersed in 0.1 mol/L pyrrole and 0.5 mol/L ammonium persulfate for 40 min in an ice/water bath. The cellulose membranes modified with polypyrrole were accommodated in a polycarbonate holder suitable for solid-phase extraction disks. Solid-phase extraction parameters that affect extraction efficiency, such as sample volume, pH, flow rate, and desorption were optimized. Subsequently, determination of target compounds was performed by gas chromatography with mass spectrometry. The linear range for analytes ranged from 0.05 to 500 MUg/L, with coefficients of determination above 0.990. The limits of quantification varied between 0.05 and 10 MUg/L, with relative standard deviations lower than 17%. The performance of the proposed cellulose membranes modified with polypyrrole device for real samples was evaluated after extraction of emerging contaminants from a river water sample from the city of Curitiba, Brazil. Bisphenol A (6.39 MUg/L), caffeine (17.83 MUg/L), and paracetamol (19.28 MUg/L) were found in these samples. PMID- 29785752 TI - Skin lesions over the pocket area that may mimic cardiac implantable electronic device infection: A case series. AB - BACKGROUND: The early and correct diagnosis of cardiac implantable electronic device (CIED) infections is critical given that early aggressive treatment with complete removal of the system along with antimicrobial therapy dramatically improves outcomes. Pocket infection manifested by local signs of inflammation is the most common form of CIED infections. Conditions mimicking pocket infection have been described in the literature. These include various types of malignancy and rarely allergic reactions/contact dermatitis to pacemaker compounds. We aimed to describe skin lesions and disorders over the pocket area that mimic CIED infection. METHODS: We present a series of five cases with skin lesions that mimic pocket infection. We document these cases with corresponding photographs. Most of them have not been described in this setting. RESULTS: We report the following cases of conditions that proved not to be CIED infection: One case of superficial cellulitis, one case of herpes zoster over the pocket area, one case of spontaneous bruising over the pocket a long time after implantation in a patient taking oral anticoagulation, and two cases of contact dermatitis due to prolonged postoperative application of povidone-iodine. All cases had favorable outcome after conservative treatment and no CIED infection was developed during follow-up. CONCLUSION: Clinicians should be aware of rare conditions that mimic CIED infection. Incorrect diagnosis of these disorders may falsely lead to CIED extraction. PMID- 29785753 TI - Relapsing polyisoprene glove allergic contact dermatitis: Another call for more complete glove package label declaration. PMID- 29785754 TI - Expression of ZO-1 and claudin-1 in a 3D epidermal equivalent using canine progenitor epidermal keratinocytes. AB - BACKGROUND: Previous studies indicate that tight junctions are involved in the pathogenesis of canine atopic dermatitis (cAD). An in vitro skin model is needed to elucidate the specific role of tight junctions in cAD. A 3D epidermal equivalent model using canine progenitor epidermal keratinocytes (CPEK) has been established; the expression of tight junctions within this model is uncharacterized. HYPOTHESIS/OBJECTIVES: To investigate the expression of tight junctions in the 3D epidermal equivalent. ANIMALS: Two normal laboratory beagle dogs served as donors of full-thickness skin biopsy samples for comparison to the in vitro model. METHODS: Immunohistochemical techniques were employed to investigate the expression of tight junctions including zonula occludens (ZO)-1 and claudin-1 in normal canine skin, and in the CPEK 3D epidermal equivalent. RESULTS: Results demonstrated the expression of ZO-1 and claudin-1 in the CPEK 3D epidermal equivalent, with staining patterns that were similar to those in normal canine skin. CONCLUSIONS AND CLINICAL IMPORTANCE: The CPEK 3D epidermal equivalent has the potential to be a suitable in vitro research tool for clarifying the specific role of tight junctions in cAD. PMID- 29785756 TI - How do we move towards a personalised approach in the treatment of Early Hodgkin lymphoma? PMID- 29785755 TI - Energy resolved mass spectrometry of chlorogenic acids and its application to isomer quantification by direct infusion tandem mass spectrometry. AB - INTRODUCTION: With the advent of high-perfomance liquid chromatography (HPLC) tandem mass spectrometry (MS) using ion trap mass analysers it is possible to acquire unambigious structural information in particular with respect to aspects of regiochemistry and stereochemistry of organic compounds present in complex mixtures such as coffee extracts. However, HPLC-MS methods are resource extensive, laborious and lacking user friendliness. OBJECTIVE: To introduce a simple parameter - the energy threshhold for fragmentation - determined using energy resolved MS and demonstrate its value for the complete structural characterisation and even relative quantification of individual isomeric chlrogenic acids in direct infusion experiments. METHODOLOGY: Monocaffeoyl and dicaffeoyl quinic acids were investigated by direct infusion energy resolved mass spectrometry (ER-MS) in negative in mode, using a quadrupole ion trap and quadrupole time-of-flight (Q-TOF) mass spectrometer. Methanolic coffee extracts were quantitatively investigated by HPLC-MS and direct infusion ER-MS. RESULTS: Fragmentation occurs with retention of regiochemistry and regiochemistry of fragment ions can be determined using ER-MS. Analysis of breakdown graphs allows extraction of a single numerical parameter that allows assignment of regiochemistry. Analysis of monocaffeoyl and dicaffeoyl quinic acids revealed that regiosiomers could be distinguished and assigned based on their dissociation energies in collisional induced activation. Furthermore relative quantification of regioisomers by direct infusion ER-MS is possible within an error range of +/ 10% if compared with a conventional quantitative LC-MS method. CONCLUSION: ER-MS can be exploited in determining relative isomers quantities of chlorogenic acids (CGAs) in crude plant extracts by direct infusion tandem MS omitting time and resource intensive chromatographic separation. PMID- 29785757 TI - A nursing solution to primary care delivery shortfall. AB - Many countries project that they will have difficulty to meet their demand for primary care based on an inadequate supply of primary care doctors. There are many reasons for this, and they tend to vary by country. The policy options available to these countries are to increase the number of local primary care doctors, recruit doctors from other countries, ration primary care, shift more primary care to specialists, or authorize other disciplines to provide primary care. This article examines lessons learned in the United States over the past 50 years and proposes that expanding the use of nurse practitioners is the best solution when measured by feasibility, costs, ethics, and scope of the care delivered. Using nurse practitioners trained in country meets the World Health Organization global code of practice regarding the international recruitment of health personnel. PMID- 29785758 TI - Undifferentiated embryonal sarcoma of liver in an adult with spontaneous rupture and tumour thrombus in the right atrium. PMID- 29785759 TI - Effect of 2.94 um Er: YAG laser on the chemical composition of hard tissues. AB - The aim was to investigate the effect of the Er-YAG laser radiation on morphology and chemical composition of enamel, dentin, and bone. The specimens of the three groups were irradiated with a very long pulse mode (VLP) of 2.94 um Er-YAG laser with 100 mJ pulse energy and energy density of 8.42 J/ cm2 for 30 s, at a repetition rate of 15 Hz. The organic and inorganic content of the samples were investigated by Fourier Transforms Infrared spectroscopy (FTIR). The morphological characteristics were investigated with scanning electron microscopy (SEM) and elemental analysis (calcium and phosphorus) with energy-dispersive X ray spectroscopy (EDX). FTIR data were analyzed with a One-Way ANCOVA test and EDX data with the independent sample t-test. Following the laser radiation, FTIR showed a significant decrease in the organic content of all tissues. The weight percentage (wt %) calcium content of dentin and bone increased significantly following irradiation with a p-value of .002 for both tissues, but the wt % of phosphorus content was not influenced significantly. The morphological alterations expressed signs of fusion in all the samples. PMID- 29785760 TI - Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark. AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease. Numerous studies have associated HS with obesity, and recently with metabolic syndrome (MetS). Both obesity and MetS are linked with metabolic changes. Thyroid hormones play a central role in metabolism and exert pleiotropic effects on adipogenesis and the basal metabolism of lipids and glucose. We hypothesized that patients with HS have an altered or dysfunctional metabolism expressed as thyroid function. AIM: To investigate thyroid function in individuals with HS compared with healthy controls (HCs). METHODS: We conducted a retrospective comparative cross-sectional study using blood samples and questionnaire-based self-reported information to assess thyroid function. RESULTS: Our study comprised 430 patients in a population-based HS group, and 20 780 HCs. The age/sex-adjusted analysis showed a significantly lower level (P < 0.001) of thyroid-stimulating hormone (TSH) and a significantly higher level (P < 0.0001) of total triiodothyronine (tT3) for the HS compared with the HC group. The age/sex-adjusted analysis also showed a significant association between clinical hyperthyroidism and HS (an OR = 1.91, 95% CI 1.19-3.07; P = 0.02). When this analysis was adjusted further for the potential confounders of body mass index, smoking and oral contraception, the results remained significant. CONCLUSION: This study suggests that HS is associated with hyperthyroidism. Hyperthyroidism may indicate an altered or dysfunctional metabolism. PMID- 29785761 TI - A novel thyroid function index associated with opposite therapeutic outcomes in advanced hepatocellular carcinoma patients receiving chemotherapy or sorafenib. AB - AIM: A sustained proportion of advanced hepatocellular carcinoma (HCC) patients worldwide received either chemotherapy or sorafenib. However, to date, effective and convenient biomarkers to predict their therapeutic outcomes remained elusive. Hypothyroidism was associated with favorable anticancer treatment outcomes in several advanced cancers. Here, we aimed to investigate the potential of using thyroid-stimulating hormone (TSH) and free T4 (FT4) levels as biomarkers to predict clinical outcomes in HCC patients receiving chemotherapy or sorafenib. METHODS: Total 123 advanced HCC patients at Barcelona Clinical Liver Cancer Stage C were included. They were separated into two cohorts, one treated by sorafenib (n = 62) and the other by chemotherapy (n = 61). Clinical data including TSH and FT4 were retrieved and correlated with treatment outcomes. RESULTS: Because of restriction in local insurance policy, the baseline liver function reserve was better in patients receiving sorafenib. Therefore, the two cohorts were analyzed separately. The results showed that a higher (> median) TSH * FT4 value was independently associated with favorable time-to-tumor progression (P = 0.006) and overall survival (P = 0.002) if chemotherapy was provided; whereas it was associated with unfavorable time-to-tumor progression (P = 0.017) and overall survival (P = 0.001) if sorafenib was administrated. These opposite associations remained valid when patients with Child-Pugh class A liver function from either cohort were included for analysis. CONCLUSION: A novel thyroid function index, TSH * FT4, significantly predicted opposite clinical outcomes in advanced HCC patients receiving sorafenib or chemotherapy treatment. PMID- 29785762 TI - Special Award in Synthetic Organic Chemistry, Japan: K. Nakanishi / Nauta Pharmacochemistry Award for Medicinal Chemistry and Chemical Biology: C. E. Muller / UCB-Ehrlich Award for Excellence in Medicinal Chemistry: A. Nelson / John C. Bailar Jr. Medal: J. F. Hartwig. PMID- 29785763 TI - Is BDNF-Val66Met polymorphism associated with psychotic experiences and psychotic disorder outcome? Evidence from a 6 years prospective population-based cohort study. AB - There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population-based prospective cohort study, the longitudinal associations between BDNF-Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case-control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re-appraisal at follow-up 6 years later (n = 254). The BDNF-Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF-Val66Met polymorphism impacted in a dose response but extra-linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum. PMID- 29785764 TI - The Effect of the 2009 USPSTF breast cancer screening recommendations on breast cancer in Michigan: A longitudinal study. AB - In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended against routine screening mammography for women age 40-49 years and against teaching self-breast examinations (SBE). The aim of this study was to analyze whether breast cancer method of presentation changed following the 2009 USPSTF screening recommendations in a large Michigan cohort. Data were collected on women with newly diagnosed stage 0-III breast cancer participating in the Michigan Breast Oncology Quality Initiative (MiBOQI) registry at 25 statewide institutions from 2006 to 2015. Data included method of detection, cancer stage, treatment type, and patient demographics. In all, 30 008 women with breast cancer detected via mammogram or palpation with an average age of 60.1 years were included. 38% of invasive cancers were identified by palpation. Presentation with palpable findings decreased slightly over time, from 34.6% in 2006 to 28.9% in 2015 (P < .001). Over the 9-year period, there was no statistically significant change in rate of palpation-detected tumors for women age <50 years or >=50 years (P = .27, .30, respectively). Younger women were more likely to present with palpable tumors compared to older women in a statewide registry. This rate did not increase following publication of the 2009 USPSTF breast cancer screening recommendations. PMID- 29785765 TI - Water Molecules Gating a Photoinduced One-Electron Two-Protons Transfer in a Tyrosine/Histidine (Tyr/His) Model of Photosystem II. AB - We investigate a biomimetic model of a TyrZ /His190 pair, a hydrogen-bonded phenol/imidazole covalently attached to a porphyrin sensitizer. Laser flash photolysis in the presence of an external electron acceptor reveals the need for water molecules to unlock the light-induced oxidation of the phenol through an intramolecular pathway. Kinetics monitoring encompasses two fast phases with distinct spectral properties. The first phase is related to a one-electron transfer from the phenol to the porphyrin radical cation coupled with a domino two-proton transfer leading to the ejection of a proton from the imidazole-phenol pair. The second phase concerns conveying the released proton to the porphyrin N4 coordinating cavity. Our study provides an unprecedented example of a light induced electron-transfer process in a TyrZ /His190 model of photosystem II, evidencing the movement of both the phenol and imidazole protons along an isoenergetic pathway. PMID- 29785767 TI - SLAMF7 (CD319/CS1) is expressed in plasmablastic lymphoma and is a potential diagnostic marker and therapeutic target. PMID- 29785768 TI - A blooming interest in the hydraulic traits of flowers. AB - This article comments on: Water relations of Calycanthus flowers: Hydraulic conductance, capacitance, and embolism resistance. PMID- 29785766 TI - Schizophyllum commune: An unexploited source for lignocellulose degrading enzymes. AB - Lignocellulose represents the most abundant source of carbon in the Earth. Thus, fraction technology of the biomass turns up as an emerging technology for the development of biorefineries. Saccharification and fermentation processes require the formulation of enzymatic cocktails or the development of microorganisms (naturally or genetically modified) with the appropriate toolbox to produce a cost-effective fermentation technology. Therefore, the search for microorganisms capable of developing effective cellulose hydrolysis represents one of the main challenges in this era. Schizophyllum commune is an edible agarical with a great capability to secrete a myriad of hydrolytic enzymes such as xylanases and endoglucanases that are expressed in a high range of substrates. In addition, a large number of protein-coding genes for glycoside hydrolases, oxidoreductases like laccases (Lacs; EC 1.10.3.2), as well as some sequences encoding for lytic polysaccharide monooxygenases (LPMOs) and expansins-like proteins demonstrate the potential of this fungus to be applied in different biotechnological process. In this review, we focus on the enzymatic toolbox of S. commune at the genetic, transcriptomic, and proteomic level, as well as the requirements to be employed for fermentable sugars production in biorefineries. At the end the trend of its use in patent registration is also reviewed. PMID- 29785769 TI - Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells. AB - Total flower extracts of Hypericum perforatum L. obtained with 3 different solvent systems were tested on tumour cell line cultures by comparing two groups of plants harvested in different times and places. The extracts, characterized according to the spectroscopic profile and the hypericin content, were tested on the growth and apoptotic death of K562 cells, a human erythroleukemic cell line. Growth and apoptosis were analysed by viable cell count, flow cytometry, and fluorescence microscopy at 6, 24, and 48 hr of culture following 1 hr exposure to the extracts under investigation. Here, we show that Hypericum extracts are able to reduce the growth of K562 cells and induce different degrees and kinetics of apoptosis according to the group of plants of origin. Also, we highlighted interesting differences in terms of efficacy among the extracts, with some samples losing their effectiveness along the culture time and others able to maintain or even increase their efficacy. Furthermore, the data herein obtained confirm the role of non hypericin compounds that are present in different proportions in the two plant groups and in the extracts analysed. PMID- 29785770 TI - Chemoprevention acceptance and adherence in women with high-risk breast lesions. AB - Patients with atypical hyperplasia and lobular carcinoma in situ (LCIS) (atypical breast lesions) are at high risk of developing breast cancer, and chemoprevention has been shown to confer a substantial reduction in that risk. Despite this, the overall rate of chemoprevention utilization in this group is low. This study evaluates the efficacy of a formal individualized education and counseling session on patient acceptance and adherence to chemoprevention. Patients with atypical breast lesions having an individualized education and counseling session in a single surgical oncology practice were prospectively entered into a database from 2001 to 2016, and with IRB approval, their data were analyzed. Chemoprevention recommendations, acceptance, duration of treatment, and side effects were recorded. A total of 536 patients were included in this study. Mean age at diagnosis was 52 years (range: 19-86 years). Chemoprevention was recommended for 386 (72%) of whom 199 (52%) elected to take medication or participate in a chemoprevention clinical trial. At the time of this writing, 72 patients had completed therapy, 69 were still in treatment, and 58 had stopped chemoprevention prematurely. Approximately 55% of the women who accepted chemoprevention in this study will complete 5 years of therapy. A formal individualized education and counseling session can improve chemoprevention acceptance and achieve a reasonable completion rate, thus reducing cancer incidence in women with atypical breast lesions. PMID- 29785771 TI - Safety and efficacy of apixaban for routine thromboprophylaxis in myeloma patients treated with thalidomide- and lenalidomide-containing regimens. PMID- 29785772 TI - Getting the picture: visual interpretation in ophthalmology residency training. AB - OBJECTIVES: Visual interpretation is essential in many fields of health care. Although diagnostic competency can be measured as an educational outcome, few accounts have addressed tacit aspects of visual interpretation in clinical training; these include the disciplining of the trainee's attentions and the trainee's acculturation into expected styles of communicating visual interpretations to others. This paper describes values and dispositions that are taught to ophthalmology trainees as they learn to reason through visual information, and explores how these qualities are evaluated during residency training. METHODS: The project was based on 6 months of ethnographic participant observation and interviews in an ophthalmology residency programme. Observational notes and interview transcripts pertaining to visual interpretation were isolated for qualitative analysis in the tradition of sociocultural anthropology, guided by literature on communication in medical education and the socialisation of health professionals. RESULTS: Residents and faculty members identified visual interpretation as one of the most challenging skills expected of ophthalmology trainees. They expressed a belief that 'systematic' approaches, where visual information is parsed in a stepwise fashion, reduce the chance of trainees overlooking or misinterpreting key diagnostic features. This sensory discipline was represented in narrative form when faculty members asked residents to interpret images aloud, as residents were expected to follow prescribed sequences for describing the content of images before commenting on possible diagnoses. CONCLUSIONS: Sensory processing is ordinarily opaque to outside observers, but the ritual of describing images in highly regimented narratives allows residents to demonstrate how they gather and reason through visual information. The form of these narratives reflects values that residents are expected to embody during their training, such as being thorough and methodical; it may also serve a pedagogical function by entrenching those values. Further research is needed to characterise how the performance of speech genres shapes the interpretive skills of medical trainees. PMID- 29785775 TI - Somatic hematopoietic TP53 mosaicism in women with breast cancer exposed to ionizing radiation. PMID- 29785774 TI - Thymol, thyme, and other plant sources: Health and potential uses. AB - Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10-64%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, anti-inflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator. In the present review, these bioactivities have been covered because some of them can contribute to explain the ethnopharmacology of thymol and its main source, T. vulgaris. Other important aspects about thymol are discussed: its toxicity and bioavailability, metabolism, and distribution in animals and humans. PMID- 29785773 TI - Molecular Tension Probes to Investigate the Mechanopharmacology of Single Cells: A Step toward Personalized Mechanomedicine. AB - Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors. Additionally, the mechanical signal is abolished using myosin inhibitors or further enhanced in the presence of inflammatory inducers, such as nicotine. Using the signal generated by the probes, single-cell dose-response measurements are performed to determine the "mechano" effective concentration (mechano-EC50 ) of albuterol, a bronchodilator, which reduces integrin forces by 50%. Mechano EC50 values for each donor present discrete readings that are differentially enhanced as a function of nicotine treatment. Importantly, donor mechano-EC50 values varied by orders of magnitude, suggesting significant variability in their sensitivity to nicotine and albuterol treatment. To the best of the authors' knowledge, this is the first study harnessing a piconewton tension sensor platform for mechanopharmacology. PMID- 29785776 TI - The Glasgow prognostic score at diagnosis is an independent predictor of survival in advanced stage classical Hodgkin lymphoma. PMID- 29785778 TI - Stakeholder identities in Britain's neoliberal ethical community: Polish narratives of earned citizenship in the context of the UK's EU referendum. AB - This article examines the narrative strategies through which Polish migrants in the UK challenge the formal rights of political membership and attempt to redefine the boundaries of 'citizenship' along notions of deservedness. The analysed qualitative data originate from an online survey conducted in the months before the 2016 EU referendum, and the narratives emerge from the open-text answers to two survey questions concerning attitudes towards the referendum and the exclusion of resident EU nationals from the electoral process. The analysis identifies and describes three narrative strategies in reaction to the public discourses surrounding the EU referendum - namely discursive complicity, intergroup hostility and defensive assertiveness - which attempt to redefine the conditions of membership in Britain's 'ethical community' in respect to welfare practices. Examining these processes simultaneously 'from below' and 'from outside' the national political community, the paper argues, can reveal more of the transformation taking place in conceptions of citizenship at the sociological level, and the article aims to identify the contours of a 'neoliberal communitarian citizenship' as internalized by mobile EU citizens. PMID- 29785779 TI - Use of silicone gel to enhance skin wound healing by secondary intention following tumour excision on the scalp and extremities. PMID- 29785777 TI - Paradoxical effect of baclofen on social behavior in the fragile X syndrome mouse model. AB - INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse. Evidence from studies in mice demonstrates that GABA, the major inhibitory neurotransmitter in the brain, and its receptors, is involved in the pathogenesis of FXS. Moreover, several FXS phenotypes, including social behavior deficits, could be corrected in Fmr1 KO mice after acute treatment with GABAB agonists. METHODS: As FXS would probably require a lifelong treatment, we investigated the effect of chronic treatment with the GABAB agonist baclofen on social behavior in Fmr1 KO mice on two behavioral paradigms for social behavior: the automated tube test and the three chamber sociability test. RESULTS: Unexpectedly, chronic baclofen treatment resulted in worsening of the FXS phenotypes in these behavior tests. Strikingly, baclofen treatment also affected wild-type animals in both behavioral tests, inducing a phenotype similar to that of untreated Fmr1 KO mice. CONCLUSION: Altogether, the disappointing results of recent clinical trials with the R baclofen enantiomer arbaclofen and our current results indicate that baclofen should be reconsidered and further evaluated before its application in targeted treatment for FXS. PMID- 29785780 TI - Electrochemical Reduction of Carbon Dioxide to Methanol on Hierarchical Pd/SnO2 Nanosheets with Abundant Pd-O-Sn Interfaces. AB - Electrochemical conversion of CO2 into fuels using electricity generated from renewable sources helps to create an artificial carbon cycle. However, the low efficiency and poor stability hinder the practical use of most conventional electrocatalysts. In this work, a 2D hierarchical Pd/SnO2 structure, ultrathin Pd nanosheets partially capped by SnO2 nanoparticles, is designed to enable multi electron transfer for selective electroreduction of CO2 into CH3 OH. Such a structure design not only enhances the adsorption of CO2 on SnO2 , but also weakens the binding strength of CO on Pd due to the as-built Pd-O-Sn interfaces, which is demonstrated to be critical to improve the electrocatalytic selectivity and stability of Pd catalysts. This work provides a new strategy to improve electrochemical performance of metal-based catalysts by creating metal oxide interfaces for selective electroreduction of CO2 . PMID- 29785781 TI - Schisantherin A protects renal tubular epithelial cells from hypoxia/reoxygenation injury through the activation of PI3K/Akt signaling pathway. AB - Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, was reported to possess anti-inflammatory and antioxidant activities. However, its protective effect against renal ischemia reperfusion (I/R) injury in human renal tubular epithelial cells subjected to hypoxia/reoxygenation (H/R) has never been studied. Thus, herein, we investigated the effect of SchA on renal I/R injury in vitro. Our results demonstrated that SchA pretreatment significantly improved HK-2 cell viability exposed to H/R. Pretreatment with SchA markedly inhibited the levels of reactive oxygen species and malondialdehyde, as well as suppressed the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and interleukin-6 in H/R-stimulated HK-2 cells. In addition, SchA also suppressed H/R-induced HK-2 cell apoptosis. Furthermore, this protective effect of SchA was mediated through the PI3K/Akt signaling pathway in HK-2 cells. These findings showed that SchA may exert a protective effect on renal tubular epithelial cells against H/R injury through the activation of PI3K/Akt signaling pathway. PMID- 29785782 TI - Path analysis of caregiver characteristics and neuropsychiatric symptoms in Alzheimer's disease patients. AB - AIM: To determine the direct and indirect relationships of sociodemographic, emotional and behavioral characteristics of family caregivers of Alzheimer's disease patients who have neuropsychiatric symptoms. METHODS: A total of 134 family caregivers answered a questionnaire with sociodemographic data, and questions regarding the context of care, Neuropsychiatric Inventory, Zarit Burden Interview, Dementia Management Strategies Scale and the Beck Depression Inventory. A path analysis was used to model the direct and indirect relationships among the selected variables. RESULTS: Being a female caregiver, presenting high levels of burden, a moderate degree of depressive symptoms, distress (Neuropsychiatric Inventory total distress score), active management strategies and criticism management strategies were significantly associated with the total score of neuropsychiatric symptoms. The caregiver burden and use of criticism management strategies were directly related to neuropsychiatric symptoms in older adults with Alzheimer's disease. The use of active management strategies and depressive symptoms of caregivers had indirect relationships with neuropsychiatric symptoms through caregiver burden. CONCLUSIONS: Overburdened caregivers and the use of dysfunctional management strategies are associated with a greater presence of neuropsychiatric symptoms in Alzheimer's disease patients. These aspects should be considered when developing interventions for caregivers to manage neuropsychiatric symptoms and overall treatment of patients with dementia. Geriatr Gerontol Int 2018; 18: 1177-1182. PMID- 29785783 TI - Silica-gelatin hybrid sol-gel coatings: A proteomic study with biocompatibility implications. AB - Osseointegration, including the foreign body reaction to biomaterials, is an immune-modulated, multifactorial, and complex healing process in which various cells and mediators are involved. The buildup of the osseointegration process is immunological and inflammation-driven, often triggered by the adsorption of proteins on the surfaces of the biomaterials and complement activation. New strategies for improving osseointegration use coatings as vehicles for osteogenic biomolecules delivery from implants. Natural polymers, such as gelatin, can mimic Collagen I and enhance the biocompatibility of a material. In this experimental study, two different base sol-gel formulations and their combination with gelatin were applied as coatings on sandblasted, acid-etched titanium substrates, and their biological potential as osteogenic biomaterials was tested. We examined the proteins adsorbed onto each surface and their in vitro and in vivo effects. In vitro results showed an improvement in cell proliferation and mineralization in gelatin-containing samples. In vivo testing showed the presence of a looser connective tissue layer in those coatings with substantially more complement activation proteins adsorbed, especially those containing gelatin. Vitronectin and FETUA, proteins associated with mineralization process, were significantly more adsorbed in gelatin coatings. PMID- 29785784 TI - Enantioselective micellar electrokinetic chromatography of dl-amino acids using (+)-1-(9-fluorenyl)-ethyl chloroformate derivatization and UV-induced fluorescence detection. AB - Chiral analysis of dl-amino acids was achieved by micellar electrokinetic chromatography coupled with UV-excited fluorescence detection. The fluorescent reagent (+)-1-(9-fluorenyl)ethyl chloroformate was employed as chiral amino acid derivatizing agent and sodium dodecyl sulfate served as pseudo-stationary phase for separating the formed amino acid diastereomers. Sensitive analysis of (+)-1 (9-fluorenyl)ethyl chloroformate-amino acids was achieved applying a xenon mercury lamp for ultraviolet excitation, and a spectrograph and charge-coupled device for wavelength-resolved emission detection. Applying signal integration over a 30 nm emission wavelength interval, signal-to-noise ratios for derivatized amino acids were up to 23 times higher as obtained using a standard photomultiplier for detection. The background electrolyte composition (electrolyte, pH, sodium dodecyl sulfate concentration, and organic solvent) was studied in order to attain optimal chemo- and enantioseparation. Enantioseparation of 12 proteinogenic dl-amino acids was achieved with chiral resolutions between 1.2 and 7.9, and detection limits for most derivatized amino acids in the 13-60 nM range (injected concentration). Linearity (coefficients of determination > 0.985) and peak-area and migration-time repeatabilities (relative standard deviations lower than 2.6 and 1.9%, respectively) were satisfactory. The employed fluorescence detection system provided up to 100-times better signal-to noise ratios for (+)-1-(9-fluorenyl)ethyl chloroformate-amino acids than ultraviolet absorbance detection, showing good potential for d-amino acid analysis. PMID- 29785785 TI - Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target. AB - Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME). Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the TME and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that TME is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including antitumor agents with those targeting stromal cell metabolism, antiangiogenic drugs, and/or immunotherapy are being developed as promising therapeutics. PMID- 29785787 TI - Expanding Systems Thinking: Incorporating Tools from Medical Sociology into MFT Education and Research. AB - The field of marriage and family therapy has historically focused on dynamics within family systems, and at times the role of social and cultural factors external to the family. To date, however, little scholarship has examined how therapists themselves are embedded within a mental healthcare system. The purpose of this article is to demonstrate how structural components of the mental healthcare system shape the practice of therapy. We draw from the field of medical sociology to illustrate how three dominant structures-managed care, diagnosis, and evidence-based models-are intertwining and mutually reinforcing systems that have significant and long-term implications for systemic therapists and researchers. We recommend incorporating a sociological understanding of such structures into MFT education and research. PMID- 29785786 TI - Aberrant chordae of the mitral valve anterior leaflet mimicking a fibroelastoma. PMID- 29785788 TI - Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta-analysis. AB - PURPOSE: We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). METHODS: We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. RESULTS: A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). CONCLUSION: Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery. PMID- 29785789 TI - American College of Cardiology 2018. AB - Ann M. Carracher, Payal H. Marathe, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Carracher, Marathe, and Close review the latest developments relevant to researchers and clinicians. PMID- 29785791 TI - Cetearyl isononanoate, an underestimated contact allergen? PMID- 29785792 TI - Gap-Mode Surface-Plasmon-Enhanced Photoluminescence and Photoresponse of MoS2. AB - 2D materials hold great potential for designing novel electronic and optoelectronic devices. However, 2D material can only absorb limited incident light. As a representative 2D semiconductor, monolayer MoS2 can only absorb up to 10% of the incident light in the visible, which is not sufficient to achieve a high optical-to-electrical conversion efficiency. To overcome this shortcoming, a "gap-mode" plasmon-enhanced monolayer MoS2 fluorescent emitter and photodetector is designed by squeezing the light-field into Ag shell-isolated nanoparticles-Au film gap, where the confined electromagnetic field can interact with monolayer MoS2 . With this gap-mode plasmon-enhanced configuration, a 110-fold enhancement of photoluminescence intensity is achieved, exceeding values reached by other plasmon-enhanced MoS2 fluorescent emitters. In addition, a gap-mode plasmon enhanced monolayer MoS2 photodetector with an 880% enhancement in photocurrent and a responsivity of 287.5 A W-1 is demonstrated, exceeding previously reported plasmon-enhanced monolayer MoS2 photodetectors. PMID- 29785794 TI - The Development of Nonanatomic Denture Occlusion: Part IV. AB - This fourth and final part of a four-part series concerned with the development of nonanatomic denture occlusion follows nonanatomic tooth design from the time of Victor Sears' first nonanatomic tooth patent through the end of the 20th century. Part IV concentrates on nonanatomic teeth developed during the last five decades of the 20th century. Many of the designs featured in this series exhibited genius, while others are pure nonsense. Sears claimed that a new nonanatomic tooth design appeared every 9 months on average during the first 30 years of nonanatomic tooth production. Many current nonanatomic tooth patents are further refinements of those earlier designs. PMID- 29785790 TI - The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults. AB - Myocardial infarction is a primary contributor towards the global burden of cardiovascular disease. Rather than repairing the existing damage of myocardial infarction, current treatments only address the symptoms of the disease and reducing the risk of a secondary infarction. Cardiac regenerative capacity is dependent on cardiomyocyte proliferation, which concludes soon after birth in humans and precocial species such as sheep. Human fetal cardiac tissue has some ability to repair following tissue damage, whereas a fully matured human heart has minimal capacity for cellular regeneration. This is in contrast to neonatal mice and adult zebrafish hearts, which retain the ability to undergo cardiomyocyte proliferation and can regenerate cardiac tissue after birth. In mice and zebrafish models, microRNAs (miRNAs) have been implicated in the regulation of genes involved in cardiac cell cycle progression and regeneration. However, the significance of miRNA regulation in cardiomyocyte proliferation for humans and other large mammals, where the timing of heart development in relation to birth is similar, remains unclear. miRNAs may be valuable targets for therapies that promote cardiac repair after injury. Therefore, elucidating the role of specific miRNAs in large animals, where heart development closely resembles that of humans, remains vitally important for identifying therapeutic targets that may be translated into clinical practice focused on tissue repair. PMID- 29785793 TI - Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis. AB - OBJECTIVE: To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. METHODS: PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and >= 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data. RESULTS: Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0 7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases. CONCLUSIONS: Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd. PMID- 29785795 TI - Isolation and Characterization of Crystalline, Neutral Diborane(4) Radicals. AB - Diaryldihalodiboranes(4) were reacted with bis(amidinato)- and bis(guanidinato)silylenes to generate the first neutral diborane-centered radicals. These formally non-aromatic 5pi electron systems are stable in the solid state as well as in solution and were characterized by solid-state structure determination, high-resolution mass spectrometry, and EPR spectroscopy. The reactivity of one of these radicals with the oxidant 1,4-benzoquinone led to ring-opening and B-O bond formation. PMID- 29785796 TI - Recent advances in understanding inheritance of holoprosencephaly. AB - Holoprosencephaly (HPE) is a complex genetic disorder of the developing forebrain characterized by high phenotypic and genetic heterogeneity. HPE was initially defined as an autosomal dominant disease, but recent research has shown that its mode of transmission is more complex. The past decade has witnessed rapid development of novel genetic technologies and significant progresses in clinical studies of HPE. In this review, we recapitulate genetic epidemiological studies of the largest European HPE cohort and summarize the novel genetic discoveries of HPE based on recently developed diagnostic methods. Our main purpose is to present different inheritance patterns that exist for HPE with a particular emphasis on oligogenic inheritance and its implications in genetic counseling. PMID- 29785797 TI - Relationship Between Handgrip Strength and Pulmonary Function in Apparently Healthy Older Women. AB - OBJECTIVES: To investigate the relationship between handgrip strength and pulmonary function. DESIGN: Cross-sectional study of a representative sample of older Korean women. SETTING: The Korean National Health and Nutrition Examination Survey. PARTICIPANTS: Community-dwelling women aged 65 and older without chronic diseases or pulmonary disease (N=605). MEASUREMENTS: Handgrip strength was measured using a digital hand dynamometer, and pulmonary function was tested according to guidelines of the American Thoracic Society/European Respiratory Society using a spirometry system. Impaired pulmonary function was defined as a lower limit of normal (LLN) or less of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Odds ratios (ORs) and 95% confidence intervals (CIs) for impaired pulmonary function according to handgrip strength quartile were calculated using multiple logistic regression analysis. RESULTS: Mean FVC and FEV1 gradually increased in accordance with handgrip strength quartiles (all P <.001). After adjusting for age, body mass index, smoking status, alcohol ingestion, aerobic physical activity, resistance exercise, household income, and education level the odds of impaired pulmonary function were greater for participants in the first quartile of handgrip strength (<=19.25 kg) than for those in the fourth quartile (25.31-37.30 kg) (FVC LLN: OR=3.46, 95 % CI=1.52-7.88; FEV1 LLN: OR=2.62, 95 % CI=1.12-6.15). CONCLUSION: Handgrip strength was positively associated with pulmonary function in a dose-dependent manner. Given the health implications of pulmonary function, timely detection of weaker handgrip strength in older people may be useful in assessing potential pulmonary function impairment. PMID- 29785798 TI - Parent-mediated intervention training delivered remotely for children with autism spectrum disorder (ASD) has preliminary evidence for parent intervention fidelity and improving parent knowledge and children's social behaviour and communication skills. PMID- 29785800 TI - Organizational models for health actions in the field of blood and blood products in Brazilian and Spanish regional contexts. AB - BACKGROUND AND OBJECTIVES: This article aims to characterize some elements that define the organizational models of healthcare actions in the field of blood and blood products. MATERIALS AND METHODS: This exploratory and qualitative study was carried out based on a documentary survey complemented by interviews with key informants of hemotherapy services from three regional territories in Spain and Brazil. RESULTS: It was evidenced demographic, territorial and organizational characteristics, as well as on instruments, resources and individuals involved in the planning, organization and implementation of services and actions in the area. DISCUSSION: The demographic characteristics and the territorial distribution showed a direct relation with the variation in the blood supply system, in the service structure and in the involvement of different individuals. The predominance of hospital services was a common feature in the territories studied, especially for transfusion services. Regionalization, centralization and concentration strategies were aimed at implementing the organization models of such services and actions in the territories. The use of planning and information technologies presents variation in the territories studied. CONCLUSION: The limits of organizational models are determined by the context and restriction of its constituent elements - structure, resources, financing, individuals involved which compromise to some degree the objectives/purposes of the policy. PMID- 29785801 TI - Gold surface plasmon crystal structure based-on polystyrene template for biosensor application. AB - In this communication, we assembled ordered polystyrene (PS) microsphere array as a template with the drop-coating method, and the oxygen plasma was used to etch the template to adjust the spacing between the PS microspheres. Nano-triangular gold array and silver nano-pyramid array were obtained by ion beam sputtering to deposit precious metal gold and silver. We observed the surface morphology of Au and Au/Ag composite films by scanning electron microscope and characterized the films by X-ray diffraction and ultraviolet/visible light spectrophotometer. The results show that the etching time of oxygen plasma has an obvious effect in adjusting the spacing between PSs and has a significant effect on the morphology of Au structure. PMID- 29785799 TI - The development of consistency and flexibility in manual pointing during middle childhood. AB - Goal-directed actions become truly functional and skilled when they are consistent yet flexible. In manual pointing, end-effector consistency is characterized by the end position of the index fingertip, whereas flexibility in movement execution is captured by the use of abundant arm-joint configurations not affecting the index finger end position. Because adults have been shown to exploit their system's flexibility in challenging conditions, we wondered whether during middle childhood children are already able to exploit motor flexibility when demanded by the situation. We had children aged 5-10 years and adults perform pointing movements in a nonchallenging and challenging condition. Results showed that end-effector errors and flexibility in movement execution decreased with age. Importantly, only the 9-10-year-olds and adults showed increased flexibility in the challenging condition. Thus, while consistency increases and flexibility decreases during mid-childhood development, from the age of nine children appear able to employ more flexibility with increasing task demands. PMID- 29785802 TI - Bayesian measurement-error-driven hidden Markov regression model for calibrating the effect of covariates on multistate outcomes: Application to androgenetic alopecia. AB - Multistate Markov regression models used for quantifying the effect size of state specific covariates pertaining to the dynamics of multistate outcomes have gained popularity. However, the measurements of multistate outcome are prone to the errors of classification, particularly when a population-based survey/research is involved with proxy measurements of outcome due to cost consideration. Such a misclassification may affect the effect size of relevant covariates such as odds ratio used in the field of epidemiology. We proposed a Bayesian measurement-error driven hidden Markov regression model for calibrating these biased estimates with and without a 2-stage validation design. A simulation algorithm was developed to assess various scenarios of underestimation and overestimation given nondifferential misclassification (independent of covariates) and differential misclassification (dependent on covariates). We applied our proposed method to the community-based survey of androgenetic alopecia and found that the effect size of the majority of covariate was inflated after calibration regardless of which type of misclassification. Our proposed Bayesian measurement-error-driven hidden Markov regression model is practicable and effective in calibrating the effects of covariates on multistate outcome, but the prior distribution on measurement errors accrued from 2-stage validation design is strongly recommended. PMID- 29785803 TI - Depressive spectrum states in a population-based cohort of 70-year olds followed over 9 years. AB - OBJECTIVE: Depression may be understood as a spectrum of more or less symptomatic states. Little is known about the long-term course of these states in older populations. We examined the prevalence and course of depressive states of different severity in a Swedish population sample of older people followed over 9 years. METHODS: A population-based sample of 70-year olds without dementia (N = 563, response rate 71.1%) underwent a psychiatric examination; 450 survivors without dementia were reexamined at ages 75 and/or 79 years. Three depressive spectrum states were defined: major depression (MD), minor depression (MIND), and subsyndromal depression (SSD). RESULTS: The cumulative 9-year prevalence of any depressive spectrum state was 55.3% (MD 9.3%, MIND 27.6%, SSD 30.9%). The cross sectional prevalence increased with age, especially for MIND and SSD. Among those with baseline MD and MIND, 75.0% and 66.7%, respectively, had MD or MIND during follow-up. Among those with SSD, 47.2% had SSD also during follow-up and 36.1% had MD or MIND. Among those with MD during follow-up, 63.1% were in a depressive spectrum state at baseline. The corresponding proportion was 30% for those with MIND (but no MD) during follow-up. CONCLUSION: In this population-based sample, over half experienced some degree of depression during their eighth decade of life. The findings give some support for the validity of a depressive spectrum in older adults. Most new episodes of major depression occurred in people who were in a depressive spectrum state already at baseline, which may have implications for late-life depression prevention strategies. PMID- 29785804 TI - Can SCSA and TUNEL forecast apoptosis-related motility depletion in Asthenozoospermia? AB - This study is an attempt to determine the power of SCSA and TUNEL for the evaluation of apoptosis status and apoptosis-related motility depletion in Asthenozoospermia. Fifty-one semen samples from Asthenozoospermic and 20 samples from fertile men participated in this study. SCSA and TUNEL were applied for the assessment of DNA integrity by flow cytometry. Annexin V conjugated with FITC labelling and FLICA method were used for the assessment of externalisation of phosphatidylserine and spermatozoon with active Caspase 3 respectively. SCSA results were shown to have a significant correlation with EPS in live spermatozoon (r = .85, p value = .00) and spermatozoon with active Caspase 3 (r = .633, p value = .00). TUNEL result was revealed to have a nonsignificant positive correlation with them. Then, Asthenozoospermic individuals were divided into two groups, SCSA higher and SCSA lower than 27%. Results interestingly indicated that the two groups significantly differed from each other in terms of TUNEL, EPS in live spermatozoon, spermatozoon with active Caspase 3 and sperm vitality (p value = .00). Both SCSA and TUNEL were correlated with apoptosis-related motility depletion in Asthenozoospermia. However, SCSA might be more powerful than TUNEL and could provide reliable information about DNA, chromatin integrity and apoptosis status in Asthenozoospermia. PMID- 29785805 TI - Fairness, severe intellectual disability, and the special case of transplantation. AB - Children with severe intellectual disability have historically been excluded from solid organ transplantation. The purpose of this article was to review the arguments for excluding this population, including claims of poorer recipient and graft survival, a lower QoL as pediatric recipients become adults, and poorer outcomes for other, more deserving pediatric transplant candidates, and make the case that these arguments are no longer persuasive. We will argue that pediatric transplant centers for reasons of social justice, value of relationships, power differential, and fairness should generally not consider intellectual ability or disability as a criterion when making decisions regarding organ transplant eligibility. PMID- 29785806 TI - Chemiluminescence of copper nanoclusters and its application for trihexyphenidyl hydrochloride detection. AB - Chemiluminescence (CL) of copper nanoclusters (CuNCs) induced by cerium (IV) (Ce(IV)) or potassium permanganate (KMnO4 ) in acidic medium was observed. The potential application of CuNCs CL in analytical chemistry was also demonstrated using trihexyphenidyl hydrochloride (THP) as an example based on its enhancing CL intensity for the CuNCs-Ce(IV)/KMnO4 systems. The excited state of the CuNCs acted as a luminophore in the CuNCs-Ce(IV) system, while CuNCs played the role of reductant in the CuNCs-KMnO4 system. The increased CL intensity for Ce(IV)-CuNCs system was proportional to the THP concentrations in the range of 0.1 to 10.0 MUM. The detection limit was 49.0 nM and the relative standard deviation was 2.2% for 2.0 MUM THP (n = 11). The proposed method was applied to detect THP in pharmaceutical formulations and human plasma samples. PMID- 29785807 TI - Renewal during functional communication training. AB - Functional communication training (FCT) is one of the most commonly prescribed interventions for the treatment of severe destructive behavior exhibited by individuals with intellectual disabilities. Although highly effective, FCT has been shown to fail in some cases when treatment is introduced into the child's typical environment. Basic and translational research on renewal provides a model for studying the relapse of destructive behavior following successful response to treatment in clinic settings using FCT. In the present study, we evaluated whether relapse of destructive behavior could be attributed to the discriminative control of the home context, which was historically correlated with reinforcement for destructive behavior. We implemented baseline contingencies in the home setting with caregivers acting as interventionists (i.e., Context A). We then implemented FCT in a treatment clinic with trained therapists (i.e., Context B). Finally, we introduced FCT in the home setting with caregivers implementing the treatment procedures (i.e., return to Context A). For three of four participants we observed the relapse of destructive behavior consistent with operant renewal. We discuss the implications of these findings with respect to strategies designed to promote generalization of FCT across settings during the treatment of severe destructive behavior. PMID- 29785809 TI - Cellulitis: what to measure, how to define? Systematic review of outcomes from cellulitis trials. PMID- 29785811 TI - After the approval of dupilumab for moderate-to-severe atopic dermatitis: what is next on the research agenda? PMID- 29785810 TI - Adjunctive therapy for healing venous leg ulcers. PMID- 29785812 TI - A role for the microbiome in psoriasis? PMID- 29785813 TI - It's the season for natural moisturizing factors and corneocyte protrusions. PMID- 29785814 TI - Botulinum toxin type A for wrinkles: the least interesting use of this versatile protein. PMID- 29785815 TI - Are European dermatology patients treated unequally? PMID- 29785816 TI - Ixekizumab or secukinumab in psoriasis: what difference does it make? PMID- 29785818 TI - Inflammatory skin eruptions induced by anti-tumour necrosis factor-alpha therapy differ undeniably from psoriasis or eczema. PMID- 29785819 TI - Editors Choice. PMID- 29785820 TI - Allocation of biologics: health economics and clinical decision making in plaque psoriasis. PMID- 29785821 TI - Optimizing photodynamic therapy regimens: variables in irradiation may influence outcomes. PMID- 29785822 TI - Cutaneous biometrics: guidelines and models. PMID- 29785823 TI - Image Gallery: Unmasking of unilateral naevoid telangiectasia during puberty. PMID- 29785824 TI - Beyond skin deep: taking bedside dermatology to the next level with noninvasive technologies. PMID- 29785825 TI - Pembrolizumab treatment of a patient with xeroderma pigmentosum with disseminated melanoma and multiple nonmelanoma skin cancers. PMID- 29785826 TI - Image Gallery: Cutaneous findings in Hunter syndrome. PMID- 29785827 TI - Image Gallery: the new age of dermoscopy: optical super-high magnification. PMID- 29785828 TI - Successful treatment with narrowband ultraviolet B phototherapy of burn-induced leucoderma. PMID- 29785829 TI - Moving core outcome sets in dermatology forward. PMID- 29785831 TI - Psoriasis: the significance of psychological stress. PMID- 29785830 TI - Image Gallery: Molluscum contagiosum-like facial lesions in a patient with a renal transplant: deep dermatophytosis due to Trichophyton rubrum. PMID- 29785832 TI - Lectin Microarray Combined with Mass Spectrometry Identifies Haptoglobin-Related Protein (HPR) as a Potential Serologic Biomarker for Separating Nonbacterial Pneumonia from Bacterial Pneumonia in Childhood. AB - PURPOSE: Etiological diagnosis of pediatric patients with community-acquired pneumonia is difficult. For therapy, one of the major problems is the difficulty in separating bacterial pneumonia which would benefit from antibiotics from nonbacterial pneumonia. Therefore, to identify potential biomarkers for distinguishing nonbacterial pneumonia from bacterial pneumonia are sought . EXPERIMENTAL DESIGN: Lectin microarray containing 91 lectins is used to screen serums from pediatric patients with pneumonia. Lectin-based pull-down assay combined with LC-MS/MS is used to identify the potential biomarkers. RESULTS: SNA I, a lectin binding preferentially to alpha2-6 linked sialic acid residues, shows higher binding signals (near 42 kDa) in the mycoplasma pneumonia group, when compared with the other groups. A total of 18 proteins are identified with LC MS/MS. By western blot analysis, the authors confirm that the expression of haptoglobin-related protein (HPR) is elevated in pediatric patients with pneumonia compared with normal children (p < 0.001). Furthermore, HPR is higher in the mycoplasma pneumonia group (p < 0.01) and the viral pneumonia group (p < 0.05), when compared with the bacterial pneumonia group. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that HPR is a potential serologic biomarker which can differentiate between bacterial pneumonia and nonbacterial pneumonia. Detection of serum HPR might be useful for clinical diagnosis. PMID- 29785833 TI - Species differences in bile acids I. Plasma and urine bile acid composition. AB - Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee. Glycine amidation was predominant in human, minipig, hamster and rabbit, while taurine amidation was predominant in mice, rat and dogs. BA profiles consisted primarily of tri-OH BAs in hamster, rat, dog and mice, di-OH BAs in human, rabbit and minipig, and mono-OH BA in chimpanzee. BA profiles comprised primarily hydrophilic and less toxic BAs in mice, rat, pig and hamster, while it primarily comprised hydrophobic and more toxic BAs in human, rabbit and chimpanzee. Therefore, the hydrophobicity index was lowest in minipig and mice, while it was highest in rabbit, monkey and human. Glucuronidation and glutathione conjugation were low in all species across all BAs. Total concentration of BAs in urine was up to 10* higher and more hydrophilic than plasma in most species. This was due to the presence of more tri-OH, amidated, sulfated and primary BAs, in urine compared to plasma. In general, BA profiles of chimpanzee and monkeys were most similar to human, while minipig, rat and mice were most dissimilar to human. PMID- 29785834 TI - Development of a robust MRI fiducial system for automated fusion of MR-US abdominal images. AB - We present the development of a two-component magnetic resonance (MR) fiducial system, that is, a fiducial marker device combined with an auto-segmentation algorithm, designed to be paired with existing ultrasound probe tracking and image fusion technology to automatically fuse MR and ultrasound (US) images. The fiducial device consisted of four ~6.4 mL cylindrical wells filled with 1 g/L copper sulfate solution. The algorithm was designed to automatically segment the device in clinical abdominal MR images. The algorithm's detection rate and repeatability were investigated through a phantom study and in human volunteers. The detection rate was 100% in all phantom and human images. The center-of-mass of the fiducial device was robustly identified with maximum variations of 2.9 mm in position and 0.9 degrees in angular orientation. In volunteer images, average differences between algorithm-measured inter-marker spacings and actual separation distances were 0.53 +/- 0.36 mm. "Proof-of-concept" automatic MR-US fusions were conducted with sets of images from both a phantom and volunteer using a commercial prototype system, which was built based on the above findings. Image fusion accuracy was measured to be within 5 mm for breath-hold scanning. These results demonstrate the capability of this approach to automatically fuse US and MR images acquired across a wide range of clinical abdominal pulse sequences. PMID- 29785836 TI - Facing death alone or together? Investigating the interdependence of death anxiety, dysfunctional attitudes, and quality of life in patient-caregiver dyads confronting lung cancer. AB - BACKGROUND: Based on the cognitive theory, anxiety arising from the awareness of death and dying may activate dysfunctional attitudes, which may then reduce quality of life. This study examined the interdependence and the mediating role of dysfunctional attitudes on the relationship between death anxiety and quality of life among patients with lung cancer and their caregivers. METHODS: From March 2016 to April 2017, 173 pairs of patients and their caregivers enrolled in a randomized controlled trial of psychosocial support. Using the baseline data, actor-partner interdependence modeling was used to analyze the relationships among death anxiety, dysfunctional attitudes, and quality of life. RESULTS: In patients, death anxiety was related to dependency (beta = .51) and self-control (beta = -.37); achievement (beta = -.21) and self-control (beta = .34) were related to quality of life. Among caregivers, death anxiety was related to all 3 dysfunctional attitudes of their own (betas = .23 to.32); dependency (beta = .22) was associated with quality of life. Caregiver quality of life was also associated with patient self-control (beta = .22) and achievement (beta = -.18). Patient self-control mediated the links between patient death anxiety with both patient and caregiver quality of life. The relationship between death anxiety and quality of life was mediated by dependency in caregivers. DISCUSSION: Death anxiety influences dysfunctional attitudes and quality of life of both patients and caregivers. Our results support the relevance of dysfunctional attitudes in understanding the impact of death anxiety and underscore the need for parallel psychosocial interventions. PMID- 29785835 TI - Predicting the ecological impacts of large-dam removals on a river network based on habitat-network structure and flow regimes. AB - Large dams provide vital protection and services to humans. However, an increasing number of large dams worldwide are old and not operating properly. The removal of large dams has excellent potential to restore habitat connectivity and flow regimes; therefore, projecting the related ecological consequences is an emerging need for water resource and ecosystem management. However, no modeling methods are currently available for such projections at the basin scale. We devised a scheme that integrates changes in flow regimes and habitat network structure into a basin-scale impact assessment of removal of large dams and applied it to the Nagara-Ibi Basin, Japan. We used a graph-theoretical approach and a hydrological model, to quantify changes in habitat availability for 11 freshwater fishes at the basin scale under multiple removal scenarios. We compared these results with the change predicted using a conventional scheme that considered only changes to the habitat network due to dam removal. Our proposed scheme revealed that an increase in flow variability associated with dam removal projected both positive and negative effects on basin-scale habitat availability, depending on the focal species, endangered species had a negative response to dam removal. In contrast, the conventional approach projected only positive effects for all species. This difference in the outcomes indicates that large-dam removal can have negative and positive effects on watershed restoration due to changes in flow regimes. Our results also suggest the effect of removal of large dams may depend on the dams and their locations. Our study is the first step in projecting ecological trade-offs associated with the removal of large dams on riverscapes at the basin scale and provides a foundation for future process-based watershed restoration. PMID- 29785837 TI - More patients reach glycaemic control with a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time-to-control analysis of LixiLan-O and LixiLan-L. AB - The present post hoc analysis of two 30-week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan-O trial) or basal insulin (LixiLan-L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) <=7.2 mmol/L, was estimated using the Kaplan-Meier method. In the LixiLan-O and LixiLan L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan-O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan-L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time-to-target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points. PMID- 29785838 TI - Learning and Processing Abstract Words and Concepts: Insights From Typical and Atypical Development. AB - The paper describes two plausible hypotheses concerning the learning of abstract words and concepts. According to a first hypothesis, children would learn abstract words by extracting co-occurrences among words in linguistic input, using, for example, mechanisms as described by models of Distributional Semantics. According to a second hypothesis, children would exploit the fact that abstract words tend to have more emotional associations than concrete words to infer that they refer to internal/mental states. Each hypothesis makes specific predictions with regards to when and which abstract words are more likely to be learned; also they make different predictions concerning the impact of developmental disorders. We start by providing a review of work characterizing how abstract words and concepts are learned in development, especially between the ages of 6 and 12. Second, we review some work from our group that tests the two hypotheses above. This work investigates typically developing (TD) children and children with atypical development (developmental language disorders [DLD] and autism spectrum disorder [ASD] with and without language deficits). We conclude that the use of strategies based on emotional information, or on co occurrences in language, may play a role at different developmental stages. PMID- 29785840 TI - Exploring photoinactivation of microbial biofilms using laser scanning microscopy and confined 2-photon excitation. AB - One pertinent complication in bacterial infection is the growth of biofilms, that is, communities of surface-adhered bacteria resilient to antibiotics. Photodynamic inactivation (PDI) has been proposed as an alternative to antibiotic treatment; however, novel techniques complementing standard efficacy measures are required. Herein, we present an approach employing multiphoton microscopy complemented with Airyscan super-resolution microscopy, to visualize the distribution of curcumin in Staphylococcus epidermidis biofilms. The effects of complexation of curcumin with hydroxypropyl-gamma-cyclodextrin (HPgammaCD) were studied. It was shown that HPgammaCD curcumin demonstrated higher bioavailability in the biofilms compared to curcumin, without affecting the subcellular uptake. Spectral quantification following PDI demonstrates a method for monitoring elimination of biofilms in real time using noninvasive 3D imaging. Additionally, spatially confined 2-photon inactivation was demonstrated for the first time in biofilms. These results support the feasibility of advanced optical microscopy as a sensitive tool for evaluating treatment efficacy in biofilms toward improved mechanistic studies of PDI. PMID- 29785839 TI - Optimization of a secondary VOI protocol for lung imaging in a clinical CT scanner. AB - We present a solution to meet an unmet clinical need of an in-situ "close look" at a pulmonary nodule or at the margins of a pulmonary cyst revealed by a primary (screening) chest CT while the patient is still in the scanner. We first evaluated options available on current whole-body CT scanners for high resolution screening scans, including ROI reconstruction of the primary scan data and HRCT, but found them to have insufficient SNR in lung tissue or discontinuous slice coverage. Within the capabilities of current clinical CT systems, we opted for the solution of a secondary, volume-of-interest (VOI) protocol where the radiation dose is focused into a short-beam axial scan at the z position of interest, combined with a small-FOV reconstruction at the xy position of interest. The objective of this work was to design a VOI protocol that is optimized for targeted lung imaging in a clinical whole-body CT system. Using a chest phantom containing a lung-mimicking foam insert with a simulated cyst, we identified the appropriate scan mode and optimized both the scan and recon parameters. The VOI protocol yielded 3.2 times the texture amplitude-to-noise ratio in the lung-mimicking foam when compared to the standard chest CT, and 8.4 times the texture difference between the lung mimicking and reference foams. It improved details of the wall of the simulated cyst and better resolution in a line-pair insert. The Effective Dose of the secondary VOI protocol was 42% on average and up to 100% in the worst-case scenario of VOI positioning relative to the standard chest CT. The optimized protocol will be used to obtain detailed CT textures of pulmonary lesions, which are biomarkers for the type and stage of lung diseases. PMID- 29785841 TI - Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment. AB - Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment. PMID- 29785842 TI - Circular RNA 0068669 as a new biomarker for hepatocellular carcinoma metastasis. AB - BACKGROUND: Circular RNAs (circRNAs) play important roles in disease occurrence. However, the roles of circRNAs in the diagnosis of hepatocellular carcinoma (HCC) are largely unknown. The aim of this study is to investigate the clinical diagnostic values of hsa_circ_0068669 (Alias: hsa_circ_103561), one of the representative HCC-associated circRNAs. METHODS: Hsa_circ_0068669 expression levels in HCC tissues, HCC cell lines, and chronic hepatitis tissues were detected by real-time quantitative reverse transcription-polymerase chain reaction. Its expression levels between HCC tissues and adjacent non-tumorous tissues were analyzed using paired t test. Independent t test and one-way analysis of variance (ANOVA) were performed to analyze the relationships between hsa_circ_0068669 expression levels and clinicopathological factors of patients with HCC. A receiver operating characteristic (ROC) curve was established to estimate the value of hsa_circ_0068669 as a biomarker in HCC. RESULTS: Hsa_circ_0068669 expression was significantly downregulated in HCC tissues and HCC cell lines compared with paired non-tumorous tissues and normal hepatic cell line, respectively. Moreover, hsa_circ_0068669 expression in HCC tissues was decreased comparing with chronic hepatitis tissues. Furthermore, hsa_circ_0068669 expression was correlated with microvascular invasion and TNM stages. CONCLUSIONS: Our findings indicate that hsa_circ_0068669 might be served as a novel potential biomarker for HCC metastasis. PMID- 29785843 TI - Insulin therapy, weight gain and prognosis. AB - Insulin therapy is mainly used by people with type 2 diabetes who have failed other therapies and have become insulin-deficient. This group represents about a quarter of all people with type 2 diabetes. Almost all those with type 2 diabetes who start insulin therapy or intensify it gain weight, which may potentially diminish the prognostic advantage of improved glycaemia. To date, all available guidelines emphasize both the attainment of glycated haemoglobin (HbA1c) goals and weight control, without directing the clinician as to which element is of a higher priority. The following review attempts to clarify the issue using the available literature. The body of evidence presented in this review indicates that glycaemic management with exogenous insulin replacement is of a much higher priority than weight gain. Lower weight or weight loss do not show prognostic benefit in advanced stages of diabetes; therefore, weight gain should not discourage providers from achieving and maintaining HbA1c goals with insulin therapy, regardless of insulin dosage or other medications. PMID- 29785844 TI - Regularity Extraction Across Species: Associative Learning Mechanisms Shared by Human and Non-Human Primates. AB - Extracting the regularities of our environment is a core cognitive ability in human and non-human primates. Comparative studies may provide information of strong heuristic value to constrain the elaboration of computational models of regularity learning. This study illustrates this point by testing human and non human primates (Guinea baboons, Papio papio) with the same experimental paradigm, using a novel online learning measure. For local co-occurrence regularities, we found similar patterns of regularity extraction in baboons and humans. However, only humans extracted the more global sequence structure. It is proposed that only the first result that is common to both species should be used to constrain models of regularity learning. The second result indicates that the extraction of global regularities cannot be accounted for by mere associative learning mechanisms and suggests that humans probably benefit from their language recoding abilities for extracting these regularities. We propose to use a comparative approach to address a series of remaining theoretical questions, which will contribute to the development of a general theory of regularity learning. PMID- 29785845 TI - Bromate and Nitrate Bioreduction Coupled with Poly-beta-hydroxybutyrate Production in a Methane-Based Membrane Biofilm Reactor. AB - This work demonstrates bromate (BrO3-) reduction in a methane (CH4)-based membrane biofilm reactor (MBfR), and it documents contrasting impacts of nitrate (NO3-) on BrO3- reduction, as well as formation of poly-beta-hydroxybutyrate (PHB), an internal C- and electron-storage material. When the electron donor, CH4, was in ample supply, NO3- enhanced BrO3- reduction by stimulating the growth of denitrifying bacteria ( Meiothermus, Comamonadaceae, and Anaerolineaceae) able to reduce BrO3- and NO3- simultaneously. This was supported by increases in denitrifying enzymes (e.g., nitrate reductase, nitrite reductase, nitrous-oxide reductase, and nitric-oxide reductase) through quantitative polymerase chain reaction (qPCR) analysis and metagenomic prediction of these functional genes. When the electron donor was in limited supply, NO3- was the preferred electron acceptor over BrO3- due to competition for the common electron donor; this was supported by the significant oxidation of stored PHB when NO3- was high enough to cause electron-donor limitation. Methanotrophs (e.g., Methylocystis, Methylomonas, and genera within Comamonadaceae) were implicated as the main PHB producers in the biofilms, and their ability to oxidize PHB mitigated the impacts of competition for CH4. PMID- 29785846 TI - D-A-D-Typed Hole Transport Materials for Efficient Perovskite Solar Cells: Tuning Photovoltaic Properties via the Acceptor Group. AB - Two D-A-D-structured hole-transport materials (YN1 and YN2) have been synthesized and used in perovskite solar cells. The two HTMs have low-lying HOMO levels and impressive mobility. Perovskite-based solar cells (PSCs) fabricated with YN2 showed a power conversion efficiency (PCE) value of 19.27% in ambient air, which is significantly higher than that of Spiro-OMeTAD (17.80%). PSCs based on YN1 showed an inferior PCE of 16.03%. We found that the incorporation of the stronger electron-withdrawing group in the HTM YN2 improves the PCE of PSCs. Furthermore, the YN2-based PSCs exhibit good long-term stability retaining 91.3% of its initial efficiency, whereas PSCs based on Spiro-OMeTAD retained only 42.2% after 1000 h lifetime (dark conditions). These promising results can provide a new strategy for the design of D-A-D HTMs for PSC applications in future. PMID- 29785848 TI - Total Synthesis of Tetarimycin A, (+/-)-Naphthacemycin A9, and (+/-)-Fasamycin A: Structure-Activity Relationship Studies against Drug-Resistant Bacteria. AB - Making use of a reductive olefin coupling reaction and Michael-Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (+/-)-naphthacemycin A9, and (+/-)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to provide related analogues for structure-activity relationship studies, thereby coming to the conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA. PMID- 29785847 TI - Impact of Water-Induced Soil Erosion on the Terrestrial Transport and Atmospheric Emission of Mercury in China. AB - Terrestrial mercury (Hg) transport, induced by water erosion and exacerbated by human activities, constitutes a major disturbance of the natural Hg cycle, but the processes are still not well understood. In this study, we modeled these processes using detailed information on erosion and Hg in soils and found that vast quantities of total Hg (THg) are being removed from land surfaces in China as a result of water erosion, which were estimated at 420 Mg/yr around 2010. This was significantly higher than the 240 Mg/yr mobilized around 1990. The erosion mechanism excavated substantial soil THg, which contributed to enhanced Hg(0) emissions to the atmosphere (4.9 Mg/yr around 2010) and its transport horizontally into streams (310 Mg/yr). Erosion-induced THg transport was driven by the extent of precipitation but was further enhanced or reduced by vegetation cover and land use changes in some regions. Surface air temperature may exacerbate the horizontal THg release into water. Our analyses quantified the processes of erosion-induced THg transport in terrestrial ecosystems, demonstrated its importance, and discussed how this transport is impacted by anthropogenic inputs and legacy THg in soils. We suggest that policy makers should pay more attention to legacy anthropogenic THg sources buried in soil. PMID- 29785849 TI - Dietary Carotenoid Roles in Redox Homeostasis and Human Health. AB - Classic nutrition believed that healthy diets should simply provide sufficient antioxidant loads to organisms, to hamper free radical processes and avoid oxidative stress. Current redox biology was proven much more intricate. Carotenoids are bioactive compounds in the human diet with a multifaceted role in redox metabolism. This perspective discusses the participation of alpha/beta carotene, lutein, zeaxanthin, lycopene, beta-cryptoxanthin, astaxanthin, and derivatives in redox homeostasis focusing on (i) their antioxidant/pro-oxidant activities, (ii) control of gene expression via Nrf2-Keap1 and NF-kappaB pathways, and (iii) their link with (sub)cellular redox circuits, as part of the "redox code" that orchestrates physiological processes and health in humans. PMID- 29785850 TI - Performance Enhancement of Inverted Perovskite Solar Cells Based on Smooth and Compact PC61BM:SnO2 Electron Transport Layers. AB - In this work, PC61BM:SnO2 electron transport layers (ETLs) were applied in inverted CH3NH3PbI3 perovskite solar cells, and a high power conversion efficiency of 19.7% could be obtained. It increased by 49.0% in comparison with the device based on PC61BM-only ETL (13.2%). SnO2 nanocrystals with excellent dispersibility were employed here to fill the pinholes and cover the valleys of PC61BM layer, forming smooth and compact PC61BM:SnO2 layers. Simultaneously, the electron traps caused by deep-level native defects of SnO2 were reduced by PC61BM, proved by the space charge limited current analysis. Thus, PC61BM:SnO2 ETLs can inhibit both of the defects in PC61BM and SnO2 layers which contribute to the electron transport improvement and reduce the recombination loss. Moreover, the device stability based on the bilayer was significantly improved in comparison with the PC61BM-only device and the performance of 85% could be maintained after 1 month. PMID- 29785851 TI - Red-Emitting Fluorescent Probe for Detection of gamma-Glutamyltranspeptidase and Its Application of Real-Time Imaging under Oxidative Stress in Cells and in Vivo. AB - gamma-Glutamyltranspeptidase (GGT) plays critical roles in regulating various physiological/pathophysiological processes including the intracellular redox homeostasis. However, an effective fluorescent probe for dissecting the relationships between GGT and oxidative stress in vivo remains largely unexplored. Herein, we present a light-up fluorescent probe (DCDHF-Glu) with long wavelength emission (613 nm) for the highly sensitive and selective detection of GGT using dicyanomethylenedihydrofuran derivative as the fluorescent reporter and gamma-glutamyl group as the enzyme-active trigger. DCDHF-Glu is competent to real time image endogenous GGT in live cells and mice. In particular, DCDHF-Glu enables the direct real-time visualization of the upregulation of GGT under drug induced oxidative stress in the HepG2 cells and the LO2 cells, as well as in vivo, vividly implying its excellent capacity in elucidation of GGT function in GGT-related biological events. PMID- 29785852 TI - Syntheses of Gibberellins A15 and A24, the Key Metabolites in Gibberellin Biosynthesis. AB - Gibberellins (GAs) are essential phytohormones involved in numerous aspects of plant growth and development. Notably, the biochemistry and genetics of GA biosynthesis, which is associated with their endogenous regulation, have been largely resolved; however, a crucial unsolved question remains: the precise mechanism of the stepwise oxidation and subsequent removal of C-20 from C20 precursors, leading to bioactive C19 gibberellins, is still unresolved. To satisfy numerous requests from biologists, practical preparations of certain GAs that were isolated in miniscule quantities are highly demanded. Herein, we report the first practical syntheses of GA15 and GA24, the key C20 metabolites in gibberellin biosynthesis, from commercially available GA3. The protocols are robust and offer the capacity to produce GA24 and GA15 under gram scales in high overall yields and thus aid in further biological and related studies. PMID- 29785854 TI - High- k Gate Dielectrics for Emerging Flexible and Stretchable Electronics. AB - Recent advances in flexible and stretchable electronics (FSE), a technology diverging from the conventional rigid silicon technology, have stimulated fundamental scientific and technological research efforts. FSE aims at enabling disruptive applications such as flexible displays, wearable sensors, printed RFID tags on packaging, electronics on skin/organs, and Internet-of-things as well as possibly reducing the cost of electronic device fabrication. Thus, the key materials components of electronics, the semiconductor, the dielectric, and the conductor as well as the passive (substrate, planarization, passivation, and encapsulation layers) must exhibit electrical performance and mechanical properties compatible with FSE components and products. In this review, we summarize and analyze recent advances in materials concepts as well as in thin film fabrication techniques for high- k (or high-capacitance) gate dielectrics when integrated with FSE-compatible semiconductors such as organics, metal oxides, quantum dot arrays, carbon nanotubes, graphene, and other 2D semiconductors. Since thin-film transistors (TFTs) are the key enablers of FSE devices, we discuss TFT structures and operation mechanisms after a discussion on the needs and general requirements of gate dielectrics. Also, the advantages of high- k dielectrics over low- k ones in TFT applications were elaborated. Next, after presenting the design and properties of high- k polymers and inorganic, electrolyte, and hybrid dielectric families, we focus on the most important fabrication methodologies for their deposition as TFT gate dielectric thin films. Furthermore, we provide a detailed summary of recent progress in performance of FSE TFTs based on these high- k dielectrics, focusing primarily on emerging semiconductor types. Finally, we conclude with an outlook and challenges section. PMID- 29785853 TI - Engineering of Porphyrin Molecules for Use as Effective Cathode Interfacial Modifiers in Organic Solar Cells of Enhanced Efficiency and Stability. AB - In the present work, we effectively modify the TiO2 electron transport layer of organic solar cells with an inverted architecture using appropriately engineered porphyrin molecules. The results show that the optimized porphyrin modifier bearing two carboxylic acids as the anchoring groups and a triazine electron withdrawing spacer significantly reduces the work function of TiO2, thereby reducing the electron extraction barrier. Moreover, the lower surface energy of the porphyrin-modified substrate results in better physical compatibility between the latter and the photoactive blend. Upon employing porphyrin-modified TiO2 electron transport layers in PTB7:PC71BM-based organic solar cells we obtained an improved average power conversion efficiency up to 8.73%. Importantly, porphyrin modification significantly increased the lifetime of the devices, which retained 80% of their initial efficiency after 500 h of storage in the dark. Because of its simplicity and efficacy, this approach should give tantalizing glimpses and generate an impact into the potential of porphyrins to facilitate electron transfer in organic solar cells and related devices. PMID- 29785856 TI - Corrigendum. PMID- 29785855 TI - Optimizing Protein Harvest From Nasal Brushings for Determining Local Allergy Responses. AB - Background Rhinitis is a highly prevalent yet often misdiagnosed condition. Patients who have local allergic rhinitis are regularly mislabeled as having a nonallergic etiology. Thus, a highly accurate, reproducible, and noninvasive assessment, which can be performed quickly and with minimal discomfort to the patient, is required. Objective The aim of this research was to identify the efficiency of various nasal brushes as tools for harvest and collection of epithelial proteins and its suitability for identification of rhinitis. Methods Nasal epithelial mucosa samples were taken from patients undergoing turbinate surgery using a cytology brush, a dental brush, and a nasal curette in random order. After washing in phosphate-buffered saline, the suspended cells were sonicated. Total protein content was assessed for all samples by bicinchoninic acid assay measured using a Nanodrop machine. Identification of nasal-specific immunoglobulin E (spIgE) was then assessed using immunoassay and compared to the patient's allergic status from epicutaneous and serum testing. The lower threshold limit for the spIgE in nasal brushings was determined using the results of serum spIgE tests as the reference. The diagnostic accuracy of this new established cutoff value was determined. Results The cytology brush was found to be the optimal tool for maximal nasal mucosa protein collection followed by dental brush and nasal curette (0.75 +/- 0.45 mg/mL vs 0.43 +/- 0.24 mg/mL vs 0.071 +/- 0.55 mg/mL, respectively; P < .01). The optimal cutoff value of nasal spIgE from the cytology nasal brushings was 0.14 kUA/L to predict allergic status from serum testing. This gave a sensitivity of 75%, specificity of 86%, positive predictive value of 74%, likelihood ration positive of 5.40, and diagnostic odds ratio of 18.62. Conclusion The cytology brush is the optimal tool for protein collection. This is an easy and direct method to sample the nasal mucosa for assessment of nasal allergy or future biomarkers. PMID- 29785857 TI - A Simulation Study on Two Analytical Techniques for Alternating Treatments Designs. AB - Alternating treatments designs (ATDs) are single-case experimental designs entailing the rapid alternation of conditions, and the specific sequence of conditions is usually determined at random. The visual analysis of ATD data entails comparing the data paths formed by connecting the measurements from the same condition. Apart from visual analyses, there are at least two quantitative analytical options also comparing data paths. On option is a visual structured criterion (VSC) regarding the number of comparisons for which one conditions has to be superior to the other to consider that the difference is not only due to random fluctuations. Another option, denoted as ALIV (a comparison involving Actual and Linearly Interpolated Values), computes the mean difference between the data paths and uses a randomization test to obtain a p value. In the current study, these two options are compared, along with a binomial test, in the context of simulated data, representing ATDs with a maximum of two consecutive administrations of the same condition and a randomized block design. Both VSC and ALIV control Type I error rates, although these are closer to the nominal 5% for ALIV. In contrast, the binomial test is excessively liberal. In terms of statistical power, ALIV plus a randomization test is superior to VSC. We recommend that applied researchers complement visual analysis with the quantification of the mean difference, as per ALIV, and with a p value whenever the alternation sequence was determined at random. We have extended an already existing website providing the graphical representation and the numerical results. PMID- 29785858 TI - Gaze Behaviors During Serve Returns in Tennis: A Comparison Between Intermediate- and High-Skill Players. AB - The authors studied gaze behaviors in high- and intermediate-skill tennis players while they performed tennis serve returns. Participants returned 40 serves in 4 serve locations while wearing a mobile eye tracker. The ball's flight path was deconstructed into 3 distinct locations (i.e., ball before bouncing on surface, the bounce area, and ball after bouncing on surface), and gaze behaviors along with quiet-eye (QE) onset and durations were recorded. Results revealed that (a) high-skill players exhibited better return shots than their lower skill counterparts, (b) high-skill players and high-score shots were characterized by longer fixation durations on the ball at prebounce, and (c) longer QE durations were observed for high-skill players and high-score shots. Findings provide valuable insight into the relationship between gaze behaviors, QE, and performance in fast-pace interceptive sports. PMID- 29785859 TI - Apposition and Positioning of the Nellix EndoVascular Aneurysm Sealing System in the Infrarenal Aortic Neck. AB - PURPOSE: To investigate the initial proximal position and seal of the Nellix EndoVascular Aneurysm Sealing (EVAS) system in the aortic neck using a novel methodology. METHODS: Forty-six consecutive patients who underwent elective EVAS for an abdominal aortic aneurysm were retrospectively selected and dichotomized into an early (n=23) and a late (n=23) group. The aortic neck morphology and aortic neck surface (ANS) were determined on preoperative computed tomography (CT) scans; the endograft position and nonapposition surface (NAS) were determined on the 1-month CT scans. The position of the proximal endobag boundary was measured by 2 experienced observers to analyze the interobserver variability for the EVAS NAS measurements. The shortest distance from the lowest renal artery to the endobag (shortest fabric distance) and the shortest distance from the endobag to the end of the infrarenal neck (shortest sealing distance) were determined. The intraclass correlation coefficients (ICCs) are presented with the 95% confidence interval (CI). Continuous data are presented as the median and interquartile range (IQR: Q3 - Q1). RESULTS: There were no differences between the early and late EVAS groups regarding aortic neck morphology except for the neck calcification circumference [41 degrees (IQR 33 degrees ) vs 87 degrees (IQR 60 degrees ), respectively; p=0.043]. Perfect agreement was observed for the NAS (ICC 0.897, 95% CI 0.780 to 0.956). The NAS as a percentage of the preoperative ANS was 47% (IQR 43) vs 49% (IQR 49) for the early vs late groups, respectively (p=0.214). The shortest fabric distances were 5 mm (IQR 5) and 4 mm (IQR 7) for the early and late groups, respectively (p=0.604); the shortest sealing distances were 9 mm (IQR 13) and 16 mm (IQR 17), respectively (p=0.066). CONCLUSION: Accurate positioning of the Nellix EVAS system in the aortic neck may be challenging. Despite considerable experience with the system, still around half of the potential seal in the aortic neck was missed in the current series, without improvement over time. This should be considered during preoperative planning and may be a cause of a higher than expected complication rate. Detailed post-EVAS nonapposition surface can be determined with the described novel methodology that takes into account the sometimes irregularly shaped top of the sealing endobags. PMID- 29785860 TI - The Development and Psychometric Properties of the Multidimensional Assessment of Teamwork in Sport. AB - The purpose of this research was to develop a questionnaire to assess the multidimensional construct of teamwork in sport and to examine various aspects of validity related to that instrument. A preliminary questionnaire was first created, and feedback on this instrument was then obtained from a sample of team sport athletes (n = 30) and experts in sport psychology (n = 8). A modified version of the questionnaire was then completed by 607 athletes from 48 teams, and 5 multilevel confirmatory factor analyses were conducted to examine the structural properties of data derived from this instrument. Evidence of adequate model-data fit along with measurement reliability was obtained for each of the 5 models. Taken together, the results from this research provide support for the content, substantive, and structural aspects of construct validity for data derived from the 66-item Multidimensional Assessment of Teamwork in Sport. PMID- 29785861 TI - Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients. AB - AIM: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients. METHODS: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR = serum albumin/total protein - serum albumin). RESULTS: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range = 0.460-3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p < .05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p = .002) and better PFS (8.0 vs 5.7 months, p < .001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p = .019, Hazard Ratio (HR) = 1.380, 95% Confidence Interval (CI) = 1.055-1.805) and PFS (p = .002, HR = 1.514, 95% CI = 1.164-1.968). CONCLUSION: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool. PMID- 29785862 TI - Cardiac MICE Associated With Left Ventricular Aneurysm. PMID- 29785863 TI - Hyperbaric oxygen inhibits production of CD3+ T cells in the thymus and facilitates malignant glioma cell growth. AB - Objective Hyperbaric oxygen (HBO) is an emerging complementary alternative medical approach in glioma treatment. However, its mode of action is unknown, so this was investigated in the present study. Methods We constructed an intracranial glioma model of congenic C57BL/6J mice. Glioma growth under HBO stimulation was assessed by bioluminescent imaging and magnetic resonance imaging. Flow cytometry assessed direct effects of HBO on reactive oxygen species (ROS) signaling of transplanted glioma cells and organs, and quantified mature T cells and subgroups in tumors, the brain, and blood. Results HBO promoted the growth of transplanted GL261-Luc glioma in the intracranial glioma mouse model. ROS signaling of glioma cells and brain cells was significantly downregulated under HBO stimulation, but thymus ROS levels were significantly upregulated. CD3+ T cells were significantly downregulated, while both Ti/Th cells (CD3+CD4+) and Ts/Tc cells (CD3+CD8+) were inhibited in tumors of the HBO group. The percentage of regulatory T cells in Ti/Th (CD3+CD4+) cells was elevated in the tumors and thymuses of the HBO group. Conclusion HBO induced ROS signaling in the thymus, inhibited CD3+ T cell generation, and facilitated malignant glioma cell growth in vivo in the intracranial glioma mouse model. PMID- 29785865 TI - An oesophageal spring. AB - Oesophageal foreign bodies (OFBs) are a relatively common emergency in young children. OFBs are complicated by significant morbidity and mortality because their ingestion often occurs without witnesses, leading to a delay in diagnosis and treatment. We report an occult OFB in an 11-month-old infant who initially presented without any specific respiratory symptoms, mimicking a respiratory infection. Worsening of the patient's cough, which did not show any improvement, despite treatment, and progressive onset of gastrointestinal manifestations (dysphagia, vomiting, and drooling) led to the diagnosis of an OFB (metallic spring). The complex and long-term clinical course of the patient highlights the need of promptly recognizing the presence of an occult OFB. This is because rapid diagnosis and treatment are essential for preventing severe and sometimes irreversible complications. PMID- 29785864 TI - Are there unmet needs in contraceptive counselling and choice? Findings of the European TANCO Study. AB - INTRODUCTION: Effective use of contraception requires women to make an informed choice about methods that match their individual needs and expectations. The European Thinking About Needs in Contraception (TANCO) study is a quantitative, online survey of healthcare provider and women's views on aspects of counselling around contraception and contraceptive use. METHODS: Healthcare providers and women attending their practices for contraceptive counselling were invited to complete online questionnaires. The women's survey explored knowledge and use of contraceptive methods, satisfaction with current method, and interest in receiving more information about all methods. Healthcare provider views were gathered in parallel. RESULTS: A total of 676 healthcare providers and 6027 women completed the online surveys in 11 countries. There was a high prevalence of contraceptive use and general satisfaction with current method across the countries. Fifty-five percent of women were using short-acting contraception (SAC) methods; 19% were using a long-acting reversible contraception (LARC) method. Sixty percent of women were interested in receiving more information about all methods; 73% of women said they would consider LARC if they received more comprehensive information. Healthcare providers tend to underestimate women's interest in receiving information on contraception in general and, more specifically, LARC methods. CONCLUSIONS: Despite high levels of use and satisfaction with current methods, women were interested in receiving more information about all contraceptive methods. Greater exploration of women's views on their needs and expectations of contraception could lead to increased knowledge, more effective discussions with healthcare providers and the greater likelihood of informed contraceptive choice. PMID- 29785867 TI - Televisits to Partially Substitute for Clinic Visits Are Feasible and Well Accepted by Tech-Savvy Patients With T1DM and Their Families: A Prospective Pilot Study. PMID- 29785866 TI - Impact of Personality Disorder Cluster on Depression Outcomes Within Collaborative Care Management Model of Care. AB - BACKGROUND: Previous studies have suggested that having a comorbid personality disorder (PD) along with major depression is associated with poorer depression outcomes relative to those without comorbid PD. However, few studies have examined the influence of specific PD cluster types. The purpose of the current study is to compare depression outcomes between cluster A, cluster B, and cluster C PD patients treated within a collaborative care management (CCM), relative to CCM patients without a PD diagnosis. The overarching goal was to identify cluster types that might confer a worse clinical prognosis. METHODS: This retrospective chart review study examined 2826 adult patients with depression enrolled in CCM. The cohort was divided into 4 groups based on the presence of a comorbid PD diagnosis (cluster A/nonspecified, cluster B, cluster C, or no PD). Baseline clinical and demographic variables, along with 6-month follow-up Patient Health Questionnaire-9 (PHQ-9) scores were obtained for all groups. Depression remission was defined as a PHQ-9 score <5 at 6 months, and persistent depressive symptoms (PDS) was defined as a PHQ-9 score >=10 at 6 months. Adjusted odds ratios (AORs) were determined for both remission and PDS using logistic regression modeling for the 6-month PHQ-9 outcome, while retaining all study variables. RESULTS: A total of 59 patients (2.1%) had a cluster A or nonspecified PD diagnosis, 122 patients (4.3%) had a cluster B diagnosis, 35 patients (1.2%) had a cluster C diagnosis, and 2610 patients (92.4%) did not have any PD diagnosis. The presence of a cluster A/nonspecified PD diagnosis was associated with a 62% lower likelihood of remission at 6 months (AOR = 0.38; 95% CI 0.20-0.70). The presence of a cluster B PD diagnosis was associated with a 71% lower likelihood of remission at 6 months (AOR = 0.29; 95% CI 0.18-0.47). Conversely, having a cluster C diagnosis was not associated with a significantly lower likelihood of remission at 6 months (AOR = 0.83; 95% CI 0.42-1.65). Increased odds of having PDS at 6-month follow-up were seen with cluster A/nonspecified PD patients (AOR = 3.35; 95% CI 1.92-5.84) as well as cluster B patients (AOR = 3.66; 95% CI 2.45-5.47). However, cluster C patents did not have significantly increased odds of experiencing persistent depressive symptoms at 6-month follow-up (AOR = 0.95; 95% CI 0.45-2.00). CONCLUSIONS: Out of the 3 clusters, the presence of a cluster B PD diagnosis was most significantly associated with poorer depression outcomes at 6-month follow up, including reduced remission rates and increased risk for PDS. The cluster A/nonspecified PD group also showed poor outcomes; however, the heterogeneity of this subgroup with regard to PD features must be noted. The development of novel targeted interventions for at-risk clusters may be warranted in order to improve outcomes of these patients within the CCM model of care. PMID- 29785868 TI - A Bowel of Flowers. PMID- 29785869 TI - Reliability and validity of the Zebris FDM-THQ instrumented treadmill during running trials. AB - Little is known about the reliability, validity and smallest detectable differences of selected kinetic and temporal variables recorded by the Zebris FDM THQ instrumented treadmill especially during running. Twenty male participants (age = 31.9 years (+/-5.6), height = 1.81 m (+/-0.08), mass = 80.2 kg (+/-9.5), body mass index = 24.53 kg/m2 (+/-2.53)) walked (5 km/h) and ran (10 and 15 km/h) on an instrumented treadmill, wearing running shoes fitted with Pedar-X insoles. A test-double retest protocol was conducted over two consecutive days. Maximal vertical force (Fmax), contact time (CT) and flight time (FT) data from 10 consecutive steps were collected. Within- and between-day reliability, smallest detectable differences (SDD) and validity (95% limits of agreement (LOA)) were calculated. ICC values for the Zebris for Fmax were acceptable (ICC >= 0.7) while CT and FT reliability indices were predominantly good (ICC >= 0.8) to excellent (ICC >= 0.9). The Zebris significantly underestimated Fmax when compared with the Pedar-X. The 95% LOA increased with speed. SDD ranged between 96 N and 169 N for Fmax, 0.017s and 0.055s for CT and 0.021s and 0.026s for FT. In conclusion, Zebris reliability was acceptable to excellent for the variables examined, but inferior in comparison with Pedar-X. With increased running speeds, a bias effect (underestimation) existed for the Zebris compared with Pedar-X. PMID- 29785870 TI - microRNAs and response to statins in patients with hypercholesterolemia: from basic research to precision medicine. PMID- 29785871 TI - Strategies to improve impact efficiency in football kicking. AB - In football, kicking with high ball velocity can increase scoring opportunities and reduce the likelihood of interception. Efficient energy transfer from foot to ball during impact is important to attain a high ball velocity. It is considered impact efficiency can be increased by reducing the change in ankle plantarflexion during foot-ball impact. However, conflicting evidence exists, questioning its effectiveness as a coaching cue. The aim of the present study was to systematically analyse joint stiffness, foot velocity and impact location with a mechanical kicking machine to determine if change in ankle plantarflexion during foot-ball impact and ball velocity are influenced. Sagittal plane data of the shank, foot and ball were measured using high-speed video (4,000 Hz). Increasing joint stiffness reduced change in ankle plantarflexion and increased ball velocity from a greater effective mass. Increasing foot velocity increased change in ankle plantarflexion and increased ball velocity. Distal impact locations increased change in ankle plantarflexion and reduced ball velocity as coefficient of restitution decreased. These results identify that change in ankle plantarflexion is a dependent variable during foot-ball impact and does not directly influence ball velocity. Coaches can assess ankle motion during impact to provide feedback to athletes on their impact efficiency. PMID- 29785872 TI - Effect evaluation on use of bedside fiber bronchoscope in treating stroke associated pneumonia. AB - Background The bedside fiber bronchoscope has been widely used in the diagnosis and treatment of respiratory disease. This study aims to assess the effect of using bedside fiber bronchoscope in sputum suction and alveolar lavage for treatment of stroke-associated pneumonia (SAP), compared with the use of conventional suction catheter. Methods One hundred and six patients with SAP were randomly divided into control group (n = 53) and experimental group (n = 53) for a controlled study. Patients in the two groups were conventionally treated with phlegm-resolving and anti-infective therapy. The conventional suction catheter was used for sputum suction for patients in the control group, while bedside fiber bronchoscope was used for sputum suction and alveolar lavage in the experimental group. Clinical pulmonary infection score (CPIS) of the two groups was carried out. The heart rate, blood gas, levels of inflammatory factors in serum, and CPIS were contrastively analyzed between the two groups. Results The blood gas (including pH, PaCO2, PaO2) levels of inflammatory factors in serum such as C-reactive protein, procalcitonin, interleukin-6 and tumor necrosis factor, and CPIS (including the third day and seventh day) in the experimental group (n = 53) were all superior to those of the control group (n = 53) (p < 0.05). The results suggested that the pulmonary ventilation condition and inflammatory response of patients with SAP were significantly improved with the use of bedside fiber bronchoscope. Conclusion The use of bedside fiber bronchoscope is beneficial in modifying the pulmonary ventilation and relieving systemic inflammatory response of patients with SAP, exhibiting a great value in clinical application. PMID- 29785873 TI - Time-out! How psychological momentum builds up and breaks down in table tennis. AB - The current study examined the development of psychological momentum (PM) in table tennis and the effect of a time-out. Eighty table tennis players were exposed to an audiovisual scenario, in which they either came back from 1-7 to 7 7 in an all-decisive game (positive momentum), or in which the opponent came back from 7-1 to 7-7 (negative momentum). Furthermore, at the score of 7-7 a time-out was called. One group of participants received no specific instructions during the time-out, whereas the other group received task (mastery-approach - MAp) instructions. Overall, PM perceptions increased for participants in the positive momentum condition, but decreased rapidly for participants in the negative momentum condition. In addition, the time-out led to a loss of PM in the positive momentum condition, but to a recovery of PM in the negative momentum condition. The instructions during the time-out did not make a significant difference. Together, these results suggest that scoring patterns in a table tennis game significantly affect the PM of players. Furthermore, a player or coach could benefit from calling a time-out in a negative momentum situation, as this provides an opportunity to psychologically recover. PMID- 29785875 TI - EGFR-TKIs in non-small-cell lung cancer: focus on clinical pharmacology and mechanisms of resistance. AB - The clinical introduction of EGFR-TKIs within the oncologic armamentarium has changed the therapeutic landscape of non-small-cell lung cancer (NSCLC) creating widespread expectations both in patients and clinicians. However, several gaps in current understanding leave open important questions regarding the use of these drugs in clinical practice. For instance, there is uncertainty in regard to which EGFR-TKI should be given first in naive patients with EGFR-driven malignancies since different generations of drugs are available with different pharmacological profiles. Furthermore, acquired drug resistance may limit the therapeutic potential of EGFR-TKIs and the choice of the best treatment strategy after first line treatment failure is still debated. This review article is aimed at describing the pharmacological properties of EGFR-TKIs and the current treatment options for NSCLC patients who develop acquired resistance. This information might be useful to design new rational and more effective pharmacological strategies in patients with EGFR-mutant NSCLC. PMID- 29785876 TI - How did Michael Jackson challenge our understanding of spine biomechanics? PMID- 29785874 TI - 'Because the baby asks for it': a mixed-methods study on local perceptions toward nutrition during pregnancy among marginalised migrant women along the Myanmar Thailand border. AB - BACKGROUND: Under- and over-nutrition during pregnancy are known risk factors for pregnancy complications and adverse pregnancy and infant outcomes. Understanding perceptions around nutrition in pregnancy can create culturally appropriate interventions for improved health outcomes. OBJECTIVE: A mixed-methods study was performed to explore local perceptions and practices of diet and physical activity in pregnancy in a marginalised population along the Myanmar-Thailand border. METHODS: From April to July 2017, a cross-sectional survey and focus group discussions were conducted with pregnant women reporting to antenatal care; in-depth interviews were conducted with senior midwives at participating organisations along the Myanmar-Thailand border. RESULTS: A total of 388 pregnant women were interviewed at two clinic sites along the Myanmar-Thailand border. A high proportion of women had limited knowledge of and poor dietary practices. Consuming a sweetened drink in the last 24 hours as well as being a non-teenage, multigravida woman was significantly associated with high body mass index (BMI) compared to normal BMI. Qualitative analysis combined focus group discussions (n = 66) and in-depth interviews (n = 4) summarising emergent themes: common foods eaten or avoided and rationale; benefits of nutrition; perceptions of overweight and weight gain during pregnancy; barriers to a healthy diet; and sources of diet information. CONCLUSIONS: There is limited awareness about healthy diets and lifestyle in these marginalised, migrant communities along the Myanmar-Thailand border. This study suggests that simple, culturally appropriate messaging should be provided to women and communities with low health literacy to generate awareness about healthy lifestyles and their effects on pregnancy outcomes as an important element of a broader strategy to address maternal nutrition in this population. However, more studies to determine the effectiveness of a broad range of interventions in low- and middle-income countries (LMIC) are needed, especially in marginalised migrant populations. PMID- 29785877 TI - Hepatitis B virus lymphotropism: emerging details and challenges. AB - The hepatitis B virus (HBV) is predominantly a hepatotropic virus but also infects cells of the lymphatic system. HBV genomes (DNA, messenger (m)RNA, covalently closed circular (ccc) DNA) and proteins have been found in extrahepatic sites such as peripheral blood mononuclear cells (PBMC), lymph nodes, spleen, bone marrow and cerebrospinal fluid. HBV entry into hepatocytes occurs by binding of the HBV preS1 surface protein to its specific receptor, the bile acid transporter, sodium taurocholate co-transporting polypeptide (NTCP). Although the mechanism of HBV entry into lymphatic cells is unknown, the pre S1 encoded surface protein is thought to be involved. Extrahepatic HBV infection has been studied in both chronic HBV (CHB) and in occult HBV infection (OBI). Studies have shown that HBV genomes are present in different PBMC subsets from chronically infected carriers. Unique HBV variants have been found in PBMC compared to plasma or liver in both nucleos(t)ide analogue (NA) treated and untreated CHB carriers, suggesting replication and compartment specific evolution of HBV. In HBV coinfection, HBV genomes were found in PBMC from hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis delta virus (HDV) co infected individuals. Moreover, during pregnancy, the trans placental passage of HBV infected PBMC from highly viremic mothers to infants is one of the postulated means of vertical transmission of HBV. Taken together, HBV infection in extrahepatic sites (i.e., PBMC) is implicated in multiple facets of HBV pathogenesis such as persistence, viral evolution and vertical transmission. PMID- 29785879 TI - Blood and hair mercury concentrations among Cree First Nations of Eeyou Istchee (Quebec, Canada): time trends, prenatal exposure and links to local fish consumption. AB - To describe exposure to methylmercury among Cree, focusing on women of childbearing age, we used data from 2 studies. Multiple regression was employed to examine associations between blood and hair mercury concentrations and consumption of locally harvested fish. Approximately 9.9% of non-pregnant women aged 15-44 y and 3.9% of pregnant women required follow-up according to Health Canada's blood mercury guidance value of 40 nmol/L. 8% of hair mercury observations in the non-pregnant women and 2.5% among pregnant women exceeded the equivalent threshold of 10 nmol/g. The geometric mean blood mercury concentration was 12.7 nmol/L in 1,429 persons aged 8 and over, and 17.7 nmol/L in adults aged 18 and older. The proportion of hair mercury concentrations greater than 12.5 nmol/g decreased in all age-sex groups when comparing the 2002-2009 data to published values for 1993-1994. Among women of childbearing age, local fish consumption was associated with increased blood and hair mercury concentrations. While over 90% of women of childbearing age in this population have acceptable levels of mercury, ongoing intake of mercury suggests that their consumption of fish with known high mercury content be minimised. Reducing consumption of fish known to be high in mercury content needs to be balanced with promoting ongoing connection to Cree culture and land-based activities that are also important determinants of health. PMID- 29785880 TI - Oxygen uptake and muscle activity limitations during stepping on a stair machine at three different climbing speeds. AB - This laboratory study examined human stair ascending capacity and constraining factors including legs' local muscle fatigue (LMF) and cardiorespiratory capacity. Twenty-five healthy volunteers, with mean age 35.3 years, maximal oxygen uptake (VO2max) of 46.7 mL.min-1.kg-1 and maximal heart rate (HR) of 190 bpm, ascended on a stair machine at 60 and 75% (3 min each) and 90% of VO2max (5 min or until exhaustion). The VO2, maximal heart rate (HRmax) and electromyography (EMG) of the leg muscles were measured. The average VO2highest reached 43.9 mL.min-1.kg-1, and HRhighest peaked at 185 bpm at 90% of VO2max step rate (SR). EMG amplitudes significantly increased at all three levels, p < .05, and median frequencies decreased mostly at 90% of VO2max SR evidencing leg LMF. Muscle activity interpretation squares were developed and effectively used to observe changes over time, confirming LMF. The combined effects of LMF and cardiorespiratory constraints reduced ascending tolerance and constrained the duration to 4.32 min. Practitioner Summary: To expedite ascending evacuation from high-rise buildings and deep underground structures, it is necessary to consider human physical load. This study investigated the limiting physiological factors and muscle activity rate changes (MARC) used in the muscle activity interpretation squares (MAIS) to evaluate leg local muscle fatigue (LMF). LMF and cardiorespiratory capacity significantly constrain human stair ascending capacities at high, constant step rates. PMID- 29785882 TI - The relationship between repetitive finger movement and quality of life in Parkinson's disease. AB - BACKGROUND: Repetitive finger movement significantly impacts daily living activities, but there have been limited studies determining how repetitive finger movement impacts quality of life (QOL) in persons with Parkinson's disease (PD). The purpose of this study was to determine the relationship between impairment in repetitive finger movement and QOL in persons with PD. METHODS: Eighty-four participants with PD completed a repetitive movement task and the Parkinson's Disease Questionnaire (PDQ). Structural equation modeling was used to determine the relationship between repetitive finger movement outcome measures of amplitude and movement rate difference and the domains of the PDQ. RESULTS: Including all repetitive finger outcome measures with demographic variables produced the strongest model for predicting QOL. DISCUSSION: Repetitive finger movement is associated with QOL, but more research is needed to better understand the relationship between repetitive finger movement variables and each specific QOL domain. PMID- 29785883 TI - What are the financial implications of the 2017 AHA/ACC High Blood Pressure Guideline? PMID- 29785881 TI - Variants in genes coding for glutathione S-transferases and asthma outcomes in children. AB - Our hypothesis was that children with mutations in genes coding for glutathione S transferases (GST) have worse asthma outcomes compared with children with active type genotype. Data were collected in five populations. The rs1695 single nucleotide polymorphism (GSTP1) was determined in all cohorts (3692 children) and GSTM1 and GSTT1 null genotype were determined in three cohorts (2362 children). GSTT1 null (but not other genotypes) was associated with a minor increased risk for asthma attack and there were no significant associations between GST genotypes and asthma severity. Interactions between GST genotypes and SHS exposure or asthma severity with the study outcomes were nonsignificant. We find no convincing evidence that the GST genotypes studied are related to asthma outcomes. PMID- 29785878 TI - Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. AB - BACKGROUND: We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS: Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, <=0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS: A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS: In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .). PMID- 29785884 TI - Morphological changes and myocardial function assessed by traditional and novel echocardiographic methods in preadolescent athlete's heart. AB - Background Athlete's heart is a term used to describe the morphological and functional changes in the hearts of athletes. Recent studies suggest that these changes may occur even in preadolescent athletes. This study aims to improve our understanding of the changes occurring in the preadolescent athlete's heart. Design and methods Cardiac morphology and function in 76 preadolescent cross country skiers (aged 12.1 +/- 0.2 years) were compared with 25 age-matched non competing preadolescents. Echocardiography was performed in all subjects, including 2D speckle-tracking strain echocardiography and 3D echocardiography. All participants underwent cardiopulmonary exercise testing to assess oxygen uptake and exercise capacity. Results Athletes had greater indexed VO2 max (62 +/ 7 vs. 44 +/- 5 mL/kg per min, p < 0.001), indexed left ventricular end-diastolic volume (79 +/- 7 vs. 68 +/- 7 mL/m2, p < 0.001), left ventricular mass (69 +/- 12 vs. 57 +/- 13 g/m2, p < 0.001), indexed right ventricular basal diameter (28.3 +/ 3.0 vs. 25.4 +/- 3.5 mm/m2, p < 0.001) and right atrial area (10.6 +/- 1.4 vs. 9.7 +/- 1.2 cm2/m2, p < 0.01). There was no difference in left ventricular ejection fraction, global longitudinal strain, and global circumferential strain and right ventricular fractional area change between the groups. Controls had higher right ventricular global longitudinal strain (-28.1 +/- 3.5 vs. -31.1 +/- 3.3%, p < 0.01). VO2 max was highly correlated to left ventricular end-diastolic volume ( r = 0.76, p < 0.001). Conclusion Athletes had greater left ventricular mass and greater left and right ventricular chamber dimensions compared with controls, while left ventricular function did not differ. Interestingly, right ventricular deformation was significantly lower compared with controls. This supports the notion that there is physiological, adaptive remodelling in preadolescent athlete's heart. PMID- 29785885 TI - Endothelial dysfunction as predictor of angina recurrence after successful percutaneous coronary intervention using second generation drug eluting stents. AB - Background The role of endothelial dysfunction in predicting angina recurrence after percutaneous coronary intervention is unknown. Design We assessed the role of peripheral endothelial dysfunction measured by reactive-hyperaemia peripheral artery tonometry (RH-PAT) in predicting recurrence of angina after percutaneous coronary intervention. Methods We enrolled consecutive patients undergoing percutaneous coronary intervention with second-generation drug-eluting stents. RH PAT was measured at discharge. The endpoint was repeated coronary angiography for angina recurrence and/or evidence of myocardial ischaemia at follow-up. Patients with in-stent restenosis and/or significant de novo stenosis were defined as having angina with obstructed coronary arteries (AOCA); all other patients as having angina with non-obstructed coronary arteries (ANOCA). Results Among 100 patients (mean age 66.7 +/- 10.4 years, 80 (80.0%) male, median follow-up 16 (3 20) months), AOCA occurred in 14 patients (14%), ANOCA in nine patients (9%). Repeated coronary angiography occurred more frequently among patients in the lower RH-PAT index tertile compared with middle and upper tertiles (14 (41.2%) vs. 6 (18.2%) vs. 3 (9.1%), p = 0.006, respectively). ANOCA was more frequent in the lower RH-PAT index tertile compared with middle and upper tertiles. In the multivariate regression analysis, the RH-PAT index only predicted angina recurrence. The receiver operating characteristic curve of the RH-PAT index to predict the angina recurrence demonstrated an area under the curve of 0.79 (95% confidence interval: 0.69-0.89; p < 0.001), with a cut-off value of 1.705, having sensitivity 74% and specificity 70%. Conclusions Non-invasive assessment of peripheral endothelial dysfunction using RH-PAT might help in the prediction of recurrent angina after percutaneous coronary intervention, thus identifying patients who may need more intense pharmacological treatment and risk factor control. PMID- 29785886 TI - Treatment of homozygous familial hypercholesterolaemia in paediatric patients: A monocentric experience. AB - Background Homozygous familial hypercholesterolaemia is a rare life-threatening disease characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) concentrations and accelerated atherosclerosis. The presence of double gene defects in the LDL-Receptor, either the same defect (homozygous) or two different LDL-raising mutations (compound heterozygotes) or other variants, identify the homozygous phenotype (HopFH). Apheresis is a procedure in which plasma is separated from red blood cells before the physical removal of LDL-C or the LDL-C is directly removed from whole blood. It is currently the treatment of choice for patients with HopFH whose LDL-C levels are not able to be reduced to target levels with conventional lipid-lowering drug therapy. Design The aim of this study is to report a cohort of six paediatric patients and to evaluate the long term efficacy of combined medical therapy and LDL-apheresis on LDL-C reduction. Methods We collected data from six children with confirmed diagnosis of HopFH (two females and four males; age range at diagnosis 3-8 years, mean 6 +/ 1 years) from a single clinical hospital in Italy from 2007 to 2017. Results Clinical manifestations and outcomes may greatly vary in children with HopFH. Medical therapy and LDL-apheresis for the severe form should be started promptly in order to prevent cardiovascular disease. Conclusions Lipoprotein apheresis is a very important tool in managing patients with HopFH at high risk of cardiovascular disease. Based on our experience and the literature data, the method is feasible in very young children, efficient regarding biological results and cardiac events, and safe with minor side-effects and technical problems. We advise treating homozygous and compound heterozygous children as soon as possible. PMID- 29785887 TI - Quality by design, process analytical technology, GMP and regulatory affairs. PMID- 29785888 TI - The impact of OPRM1's genetic polymorphisms on methadone maintenance treatment in opioid addicts: a systematic review. AB - AIM: Methadone is a long-acting opioid receptor agonist. It is prescribed to patients with opioid-related use disorders. The OPRM1 gene encodes for methadone's main receptor. It appears that polymorphisms in OPRM1 may affect the efficacy of methadone maintenance treatment (MMT). OBJECTIVE: Our purpose was to identify all relevant published papers dealing with the impact ofOPRM1's SNPs on MMT's efficacy and to summarize results in order to evaluate the relevance of conducting pretherapeutic genotyping in opioid addicts prior to the onset of MMT. METHODS: MEDLINE, PsychINFO and Scopus databases were systematically searched up to 1 January 2018 with no year restrictions using the following keyword combination (MMT) AND (mu or OPRM or mu opioid receptors or SNP or polymorphism or gene). Endpoint of the included studies had to be the impact of OPRM1 gene polymorphisms on the efficacy of MMT and/or methadone required doses during MMT. All abstracts were reviewed to assess papers' relevance. Studies conducted on animals and duplicate papers were excluded. RESULTS: Our literature search identified 438 articles. Eight of them were included in our systematic review. The total number of included participants was equal to 2170, of whom 1718 underwent MMT. One study reported results of a randomized controlled trial. Three were designed as case-control studies and four as cross-sectional studies. rs1799971 (A118G) was the most studied allele. Results were divergent. Other SNPs might affect MMT's efficacy, however they were scarcely studied. CONCLUSION: Genotyping patients with opioid-related use disorders is a promising way to reach a better outcome in patients willing to be on MMT. Focusing on OPRM1 solely should be balanced since polymorphisms in other genes implicated in methadone pharmacodynamics and/or pharmacokinetics may conjunctly affect the efficacy of MMT. Recommendations cannot be enunciated for the moment. PMID- 29785889 TI - Effects of probiotic supplementation on performance traits, bone mineralization, cecal microbial composition, cytokines and corticosterone in laying hens. AB - Recent researches have showed that probiotics promote bone health in humans and rodents. The objective of this study was to determine if probiotics have the similar effects in laying hens. Ninety-six 60-week-old White Leghorn hens were assigned to four-hen cages based on their BW. The cages were randomly assigned to 1 of 4 treatments: a layer diet mixed with a commercial probiotic product (containing Enterococcus faecium, Pediococcus acidilactici, Bifidobacterium animalis and Lactobacillus reuteri) at 0, 0.5, 1.0 or 2.0 g/kg feed (Control, 0.5*, 1.0* and 2.0*) for 7 weeks. Cecal Bifidobacterium spp. counts were higher in all probiotic groups (P0.05). In addition, the plasma concentrations of cytokines (interleukin-1beta, interleukin-6, interleukin-10, interferon-gamma and tumor necrosis factor-alpha) and corticosterone as well as the levels of heterophil to lymphocyte ratio were similar between the 2.0* group and the control group (P>0.05). In line with these findings, no differences of cecal tonsil mRNA expressions of interleukin-1beta, interleukin-6 and lipopolysaccharide-induced tumor necrosis factor-alpha factor were detected between these two groups (P>0.05). These results suggest that immune cytokines and corticosterone may not involve in the probiotic-induced improvement of eggshell quality and bone mineralization in laying hens. In conclusion, the dietary probiotic supplementation altered cecal microbiota composition, resulting in reduced shell-less egg production and improved bone mineralization in laying hens; and the dietary dose of the probiotic up to 2.0* did not cause negative stress reactions in laying hens. PMID- 29785890 TI - Family networks and healthy behaviour: evidence from Nepal. AB - Models of household decision-making commonly focus on nuclear family members as primary decision-makers. If extended families shape the objectives and constraints of households, then neglecting the role of this network may lead to an incomplete understanding of health-seeking behaviour. Understanding the decision-making processes behind care-seeking may improve behaviour change interventions, better intervention targeting and support health-related development goals. This paper uses data from a cluster randomised trial of a participatory learning and action cycle (PLA) through women's groups, to assess the role of extended family networks as a determinant of gains in health knowledge and health practice. We estimate three models along a continuum of health-seeking behaviour: one that explores access to PLA groups as a conduit of knowledge, another measuring whether women's health knowledge improves after exposure to the PLA groups and a third exploring the determinants of their ability to act on knowledge gained. We find that, in this context, a larger network of family is not associated with women's likelihood of attending groups or acquiring new knowledge, but a larger network of husband's family is negatively associated with the ability to act on that knowledge during pregnancy and the postpartum period. PMID- 29785891 TI - Performance and carcass characteristics of steers fed with two levels of metabolizable energy intake during summer and winter season. AB - Climate change is producing an increase on extreme weather events around the world such as flooding, drought and extreme ambient temperatures impacting animal production and animal welfare. At present, there is a lack of studies addressing the effects of climatic conditions associated with energy intake in finishing cattle in South American feed yards. Therefore, two experiments were conducted to assess the effects of environmental variables and level of metabolizable energy intake above maintenance requirements (MEI) on performance and carcass quality of steers. In each experiment (winter and summer), steers were fed with 1.85 or 2.72 times of their requirements of metabolizable energy of maintenance. A total of 24 crossbred steers per experiment were used and located in four pens (26.25 m2/head) equipped with a Calan Broadbent Feeding System. Animals were fed with the same diet within each season, varying the amount offered to adjust the MEI treatments. Mud depth, mud scores, tympanic temperature (TT), environmental variables, average daily gain, respiration rates and carcass characteristics plus three thermal comfort indices were collected. Data analysis considered a factorial arrangement (Season and MEI). In addition, a repeated measures analysis was performed for TT and respiration rate. Mean values of ambient temperature, solar radiation and comfort thermal indices were greater in the summer experiment as expected (P<0.005). The mean values of TT were higher in steers fed with higher MEI and also in the summer season. The average daily gain was greater during summer v. winter (1.10+/-0.11 v. 0.36+/-0.06) kg/day, also when steers were fed 2.72 v. 1.85 MEI level (0.89+/-0.12 v. 0.57+/-0.10) kg/day. In summer, respiration rate increased in 41.2% in the afternoon. In winter, muddy conditions increased with time of feeding, whereas wind speed and rainfall had significant effects on TT and average daily gain. We conclude that MEI and environmental variables have direct effects on the physiology and performance of steers, including TT and average daily gain, particularly during the winter. In addition, carcass characteristics were affected by season but not by the level of MEI. Finally, due to the high variability of data as well as the small number of animals assessed in these experiments, more studies on carcass characteristics under similar conditions are required. PMID- 29785892 TI - The monogenean Paradiplozoon ichthyoxanthon behaves like a micropredator on two of its hosts, as indicated by stable isotopes. AB - The analysis of stable isotopes of carbon and nitrogen has been used as a fingerprint for understanding the trophic interactions of organisms. Most of these studies have been applied to free-living organisms, while parasites have largely been neglected. Studies dealing with parasites so far have assessed the carbon and nitrogen signatures in endoparasites or ectoparasites of different hosts, without showing general trends concerning the nutritional relationships within host-parasite associations. Moreover, in most cases such systems involved a single host and parasite species. The present study is therefore the first to detail the trophic interactions of a freshwater monogenean-host model using delta13C and delta15N, where a single monogenean species infects two distinctly different hosts. Host fishes, Labeobarbus aeneus and Labeobarbus kimberleyensis from the Vaal Dam, South Africa, were assessed for the monogenean parasite Paradiplozoon ichthyoxanthon, individuals of which were removed from the gills of the hosts. The parasites and host muscle samples were analysed for signatures of delta13C and delta15N using an elemental analyser connected to an isotope ratio mass spectrometer. Host fish appear to use partly different food sources, with L. aeneus having slightly elevated delta13C signatures compared to L. kimberleyensis, and showed only small differences with regard to their nitrogen signatures, suggesting that both species range on the same trophic level. Carbon and nitrogen signatures in P. ichthyoxanthon showed that the parasites mirrored the small differences in dietary carbon sources of the host but, according to delta15N signatures, the parasite ranged on a higher trophic level than the hosts. This relationship resembles predator-prey relationships and therefore suggests that P. ichthyoxanthon might act as a micropredator, similar to blood sucking arthropods such as mites and fleas. PMID- 29785893 TI - Evaluating vaccination strategies to control foot-and-mouth disease: a country comparison study. AB - Vaccination is increasingly being recognised as a potential tool to supplement 'stamping out' for controlling foot-and-mouth disease (FMD) outbreaks in non endemic countries. Infectious disease simulation models provide the opportunity to determine how vaccination might be used in the face of an FMD outbreak. Previously, consistent relative benefits of specific vaccination strategies across different FMD simulation modelling platforms have been demonstrated, using a UK FMD outbreak scenario. We extended this work to assess the relative effectiveness of selected vaccination strategies in five countries: Australia, New Zealand, the USA, the UK and Canada. A comparable, but not identical, FMD outbreak scenario was developed for each country with initial seeding of Pan Asia type O FMD virus into an area with a relatively high density of livestock farms. A series of vaccination strategies (in addition to stamping out (SO)) were selected to evaluate key areas of interest from a disease response perspective, including timing of vaccination, species considerations (e.g. vaccination of only those farms with cattle), risk area vaccination and resources available for vaccination. The study found that vaccination used with SO was effective in reducing epidemic size and duration in a severe outbreak situation. Early vaccination and unconstrained resources for vaccination consistently outperformed other strategies. Vaccination of only those farms with cattle produced comparable results, with some countries demonstrating that this could be as effective as all species vaccination. Restriction of vaccination to higher risk areas was less effective than other strategies. This study demonstrates consistency in the relative effectiveness of selected vaccination strategies under different outbreak start up conditions conditional on the assumption that each of the simulation models provide a realistic estimation of FMD virus spread. Preferred outbreak management approaches must however balance the principles identified in this study, working to clearly defined outbreak management objectives, while having a good understanding of logistic requirements and the socio-economic implications of different control measures. PMID- 29785894 TI - Developmental and molecular responses of buffalo (Bubalus bubalis) cumulus-oocyte complex matured in vitro under heat shock conditions. AB - SummaryTo investigate the effects of physiologically relevant heat shock during oocyte maturation, buffalo cumulus-oocyte complexes (COCs) were cultured at 38.5 degrees C (control) or were exposed to 39.5 degrees C (T1) or 40.5 degrees C (T2) for the first 6 h of in vitro maturation (IVM), followed by 38.5 degrees C through the next 18 h/IVM and early embryonic development up to the blastocyst stage. Gene expression analysis was performed on selected target genes (HSF-1, HSF-2, HSP-70, HSP-90, BAX, p53, SOD1, COX1, MAPK14) in denuded oocytes and their isolated cumulus cells resulting from control COCs as well as from COCs exposed to a temperature of 39.5 degrees C (T1). The results indicated that heat shock significantly (P < 0.01) decreased the maturation rate in T1 and T2 cells compared with the control. After in vitro fertilization (IVF), cleavage rate was lower (P < 0.01) for oocytes exposed to heat stress, and the percentage of oocytes arrested at the 2- or 4-cell stage was higher (P < 0.01) than that of the control. The percentage of oocytes that developed to the 8-cell, 16-cell or blastocyst stage was lower (P < 0.01) in both T1 and T2 groups compared with the control group. mRNA expression levels for the studied genes were decreased (P < 0.05) in treated oocytes (T1) except for HSP-90 and HSF-1, which were increased. In cumulus cells isolated from COCs (T1), the expression for the target genes was upregulated except for BAX, which was downregulated. The results of this study demonstrated that exposure of buffalo oocytes to elevated temperatures for 6 h severely compromised their developmental competence and gene expression. PMID- 29785895 TI - Complexity in pediatric primary care. AB - BACKGROUND: The management of patients in primary care is often complicated by the presence of multiple chronic conditions and psychosocial issues that increase the complexity of the encounter and have important impacts on care. There is a paucity of literature on this subject in the pediatric population. OBJECTIVES: The aim of this study was to quantify the burden of chronic conditions in pediatric primary care. METHODS: The problem lists of 3995 randomly selected patients from a community pediatric clinic and an academic hospital-based pediatric clinic in the same metropolitan area were analyzed for the presence and number of any chronic condition. RESULTS: In total, 53% of patients suffered from at least one chronic problem, 25% had two or more chronic conditions and 5.1% had four or more conditions. Compared with the community clinic, the academic clinic had significantly more children with catastrophic complex conditions (P<0.001). A regression analysis showed a significant positive correlation between the number of chronic medical conditions and mental health diagnoses. CONCLUSIONS: The burden of chronic disease in the pediatric primary care setting may be significantly higher than has been previously suggested. To ensure optimal quality of care, health planners should take into account the high burden of chronic illness, psychosocial issues and multimorbidity among patients in the pediatric primary care setting, as well as the higher complexity profile of patients attending academic clinics. PMID- 29785896 TI - Survey of trematodes in intertidal snails from Patagonia, Argentina: new larval forms and diversity assessment. AB - Larval trematodes are the main parasites of snails, and they play a crucial role because they usually castrate their snail hosts and can thus alter their population and community dynamics. This study involved a survey of seven gastropod species (Crepipatella dilatata, Fissurella radiosa, Nacella magellanica, Pareuthria fuscata, Siphonaria lessonii, S. lateralis and Trophon geversianus) parasitized by 12 trematode species (one hemiurid, one gymnophallid, two lepocreadiids, two microphallids, one notocotylid, two renicolids, one philophtalmid, one schistosomatid and one zoogonid) from southern Patagonia (47 degrees S, 65 degrees W), Argentina. Only F. radiosa was free of parasites. The study included the description of five new larvae, based on morphological and molecular information, and a comparison of the parasite diversity with that of a northern locality (42 degrees S, 64 degrees W), characterized by a lower mollusc diversity. Species richness and diversity of parasites were higher in the southern site. This suggests a correlation between the level of parasitism and the diversity of molluscs (first intermediate hosts), which is higher at the high latitude site and seems to attract shorebirds, which disperse the digenean eggs and facilitate the completion of their life cycles. These results support the notion that parasitism is influenced by large-scale factors such as biogeographical patterns, and small-scale factors such as diversity or abundance of intermediate and definitive hosts. PMID- 29785898 TI - Accuracy and application of milk fatty acid estimation with diffuse reflectance near-infrared spectroscopy. AB - Near infrared spectroscopy (NIRS) has the potential to estimate contents of fatty acids (FA) in milk frequently at-farm or during daily milking routine. In this study, a total of 738 raw milk spectra collected from 33 Holstein cows over a period of 30 weeks were recorded. Reference data on FA composition in milk and in milk fat were analysed in laboratory. Calibration models were calculated for single FA and groups of FA in milk and in milk fat. Validation resulted in sufficient Ratio of Prediction to Deviation (RPD) values for some single FA and in higher RPD values for groups of FA when concentrations of FA in milk were predicted. Since the concentrations of most FA in milk are highly correlated with milk fat content, the prediction of FA contents in milk fat is more meaningful when independent predictions are intended. The accuracy of predicting single FA concentrations in milk fat is rather poor for most FA but still comparable to alternative analysing methods such as MIR analysis. The estimation of different groups of FA in milk fat resulted in an improved accuracy based on higher RPD values, which was sufficient to mirror the development in the different lactation phases. The course of cow individual long chain fatty acid (LCFA) concentration in the early lactation stage can be an indicator for body fat mobilisation. The accurate estimation of the extent and duration of body fat mobilisation in cow individuals was rather difficult with NIR predicted LCFA concentrations and would require a higher measuring frequency than applied in this study. PMID- 29785897 TI - Addition of pectin and whey protein concentrate minimises the generation of acid whey in Greek-style yogurt. AB - The objective of the study reported in this Research Communication was to investigate the effects of pectin and whey protein concentrate (WPC) on the generation of acid whey during Greek-style yogurt (GSY) processing. Yogurt samples were prepared using pectin (0.05%, w/v) and whey protein concentrate (WPC 80) (1%, w/v) as possible ingredients that reduce the acid whey production. Control yogurt sample was prepared without addition of these ingredients. The results showed that yogurt made with pectin plus WPC had significantly higher water holding capacity (~56%) than the control (33%). Similarly, yogurt supplemented with pectin plus WPC exhibited 15% less susceptibility to syneresis compared to the control (P < 0.05). Viability of L. bulgaricus and S. thermophilus in all yogurts remained >=7.0 and >=8.0 log CFU/g respectively. Native PAGE analysis showed an interaction between pectin and WPC. Pectin hinders the formation of large oligomeric aggregates of whey protein which correlates with an increase in WHC and a decrease in syneresis. Our results demonstrated that a combination of pectin and WPC have the potential to limit the quantity of acid whey generation in GSY manufacturing. Thus, these ingredients have positive implications for dairy industry in the production of GSY. PMID- 29785899 TI - RagD regulates amino acid mediated-casein synthesis and cell proliferation via mTOR signalling in cow mammary epithelial cells. AB - This research paper addresses the hypothesis that RagD is a key signalling factor that regulates amino acid (AA) mediated-casein synthesis and cell proliferation in cow mammary epithelial cells (CMECs). The expression of RagD was analysed at different times during pregnancy and lactation in bovine mammary tissue from dairy cows. We showed that expression of RagD at lactation period was higher (P < 0.05) than that at pregnancy period. When CMECs were treated with methionine (Met) or lysine (Lys), expression of RagD, beta-casein (CSN2), mTOR and p-mTOR, and cell proliferation were increased. Further, when CMECs were treated to overexpress RagD, expression of CSN2, mTOR and p-mTOR, and cell proliferation were up-regulated. Furthermore, the increase in expression of CSN2, mTOR and p mTOR, and cell proliferation in response to Met or Lys supply was inhibited by inhibiting RagD, and those effects were reversed in the overexpression model. When CMECs were treated with RagD overexpression together with mTOR inhibition or conversely with RagD inhibition together with mTOR overexpression, results showed that the increase in expression of CSN2 and cell proliferation in response to RagD overexpression was prevented by inhibiting mTOR, and those effects were reversed by overexpressing mTOR. The interaction of RagD with subunit proteins of mTORC1 was analysed, and the result showed that RagD interacted with Raptor. CMECs were treated with Raptor inhibition, and the result showed that the increase in expression of mTOR and p-mTOR in response to RagD overexpression was inhibited by inhibiting Raptor.In conclusion, our study showed that RagD is an important activation factor of mTORC1 in CMECs, activating AA-mediated casein synthesis and cell proliferation, potentially acting via Raptor. PMID- 29785900 TI - Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows. AB - Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKalpha) activator). The results showed that insulin decreased AMPKalpha phosphorylation. This inactivation of AMPKalpha increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKalpha inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-alpha (PPARalpha), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKalpha induced by AICAR could reverse the effect of insulin on PPARalpha, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKalpha signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis. PMID- 29785901 TI - Association of SNP and STR polymorphisms of insulin-like growth factor 2 receptor (IGF2R) gene with milk traits in Holstein-Friesian cows. AB - The objective of the study reported in this Research Communication was to investigate the association of polymorphisms in the insulin-like growth factor receptor 2 (IGF2R) gene with milk traits in 283 Polish Holstein-Friesian (PHF) cows from the IGAB PAS farm in Jastrzebiec. IGF2R regulates the availability of biologically active IGF2 which is considered as a genetic marker for milk or meat production in farm animals. Two novel genetic polymorphisms were identified in the bovine IGF2R gene: a polymorphic TG-repeat in intron 23 (g.72389 (TG)15-67), and a g.72479 G > A SNP RFLP-StyI in exon 24. The following milk traits were investigated: milk yield, protein and fat yield, SCC and lactose content. To determine the influence of the IGF2R STR and SNP genotypes on the milk traits, we used the AI-REML (average information restricted maximum likelihood) method with repeatability, multi-trait animal model based on test-day information using DMU package. Statistical analysis revealed that the G/A genotype (P <= 0.01) was associated with milk and protein yield, lactose content and somatic cell count (SCC) in Polish HF cows. TGn (29/22, 28/29, 28/22, 28/28) genotypes were associated with high values for milk, (28/22, 28/23) with protein and fat yield, (25/20) with lactose content, and (29/33, 28/28) with low SCC. We suggest that the IGF2R gene polymorphisms could be useful genetic markers for dairy production traits in cattle. PMID- 29785902 TI - Milk microRNA-146a as a potential biomarker in bovine tuberculosis. AB - In this research communication we exploited the potential use of milk microRNAs (miRs) as biomarkers for bovine tuberculosis (bTB). bTB is a zoonotic disease caused by Mycobacterium bovis which affects animal health, influencing herd economic sustainability. Diagnosis is based on skin delayed-type hypersensitivity reaction and quantification of interferon gamma but both techniques are influenced by several confounding factors. Thus, new methods for early diagnosis are required. In this context, microRNAs have been used as promising biomarkers for both infectious and non-infectious diseases. To determine the possible involvement of microRNAs in bTB, we analysed the expression of four immune related miRs in 200 cows grouped in cases and controls with respect to positivity to tuberculosis. The analysis showed a different magnitude of expression in the groups indicating that active tuberculosis could influence miRs expression. We used expression values of miR-146a, the highest differentially expressed miR, for Receiver operating characteristic (ROC) curve analysis. In order to determine a test cut-off value for miR-146a expression that would differentiate cases and controls, a value for the miR-146a expression higher than 8 was selected as this gave a test specificity and sensitivity of 80.0% and 86.0% respectively. These values confirm the possibility of using miR-146a as a milk prognostic biomarker for bovine tuberculosis. PMID- 29785903 TI - High intensity light pulses to reduce microbial load in fresh cheese. AB - The present study focused on the utilisation of High Intensity Light Pulses (HILP) treatment to preserve mozzarella cheese. First, the susceptibility of Pseudomonas fluorescens and Enterobacteriaceae to HILP (fluences from 0.39 to 28.0 J/cm2) in a transparent liquid was evaluated (in-vitro tests). Afterwards, the effects on inoculated mozzarella cheese were also assessed. Then untreated (Control) and HILP treated samples were packaged and stored at 10 degrees C for 2 weeks. Enterobacteriaceae, Pseudomonas spp. and pH were monitored during storage. In a transparent liquid (in-vitro tests) there was a significant microbial inactivation just with 2 s of treatment. On the inoculated cheese a relevant microbial reduction of about 1 log cycle was observed, according to the exposure to the treatments. For Pseudomonas spp. in particular, in the treated samples, the microbiological acceptability limit (106 cfu/g) was never reached after 2 weeks of refrigerated storage. To sum up, the efficacy of this treatment is very interesting because a microbial reduction was observed in treated samples. HILP treatment is able to control the microbial growth and may be considered a promising way to decontaminate the surface of mozzarella cheese. PMID- 29785904 TI - Identification of an immune modulation locus utilising a bovine mammary gland infection challenge model. AB - Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd. A total of 604 animals received an intramammary infusion of Streptococcus uberis in one gland, and the clinical response over 13 milkings was used for linkage mapping and genome-wide association analysis. A quantitative trait locus (QTL) was detected on bovine chromosome 11 for clinical mastitis status using micro-satellite and Affymetrix 10 K SNP markers, and then exome and genome sequence data used from the six F1 sires of the experimental animals to examine this region in more detail. A total of 485 sequence variants were typed in the QTL interval, and association mapping using these and an additional 37 986 genome wide markers from the Illumina SNP50 bovine SNP panel revealed association with markers encompassing the interleukin-1 gene cluster locus. This study highlights a region on bovine chromosome 11, consistent with earlier studies, as conferring resistance to experimentally induced mammary gland infection, and newly prioritises the IL1 gene cluster for further analysis in genetic resistance to mastitis. PMID- 29785905 TI - Hepatic Sirt3 expression declines postpartum in dairy goats. AB - The experiments reported in this research communication aimed to plot the expression pattern of Sirt3, a master regulator of energy metabolism and antioxidation defence, in the liver of dairy goats during perinatal period. Ten healthy dairy goats in late pregnancy were chosen, and needle biopsy was applied to collect liver samples at 1-week intervals. Protein levels of hepatic Sirt3 were analysed by western-blotting. Serum enzyme activities of manganese superoxide dismutase (Mn-SOD) and non-esterified fatty acids (NEFA) levels were measured, and their correlation with Sirt3 mRNA levels was also estimated. Compared with >3-week before parturition (BP), Sirt3 proteins were significantly reduced at 1-week after parturition (AP) and 2-week AP (P < 0.05), but increased on the day of parturition (P < 0.01). Correlation analysis revealed a positive association between hepatic Sirt3 mRNA levels and serum enzyme activity of Mn-SOD (r = 0.46), but a negative association between that and serum NEFA levels (r = 0.41). These data indicate that the decreased hepatic expression of Sirt3 might be one of the reasons that dairy goats undergo oxidative stress after parturition. PMID- 29785906 TI - Molecular characterisation of the buffalo SCAP gene and its association with milk production traits in water buffaloes. AB - The study reported in this Research Communication was conducted to investigate the molecular characterisation of buffalo SCAP gene, expression analysis, and the association between single nucleotide polymorphisms and milk production traits in 384 buffaloes. Sequence analysis revealed the SCAP gene had an open reading frame of 3837 bp encoding 1279 amino acids. A ubiquitous expression profile of SCAP gene was detected in various tissues with extreme predominance in the mammary gland during early lactation. Moreover, eleven SNPs in buffalo SCAP gene were identified, six of them (g.1717600A>G, g.1757922C>T, g.1758953G>A, g.1759142C>T, g.1760740G>A, and g.1766036T>C) were found to be significantly associated with 305-day milk yield. Thus, buffalo SCAP could sever as a candidate gene affecting milk production traits in buffalo and the identified SNPs might potentially be genetic markers. PMID- 29785908 TI - Rapid detection of adulteration of milks from different species using Fourier Transform Infrared Spectroscopy (FTIR). AB - The aim of the studies reported in the Research Communication was to develop a rapid spectroscopic technique as an alternative method for the classification and discrimination of milk sources by Fourier transform infrared spectroscopy (FTIR). Cow, sheep and water buffalo milk samples were collected from various local milk producers in Istanbul, Turkey. In addition, various brands of packaged milk were purchased locally. Spectrums were obtained according to milk species origin and binary mixtures prepared in increments of 10% (10, 20, 30, 40, 50, 60, 70, 80 and 90%) for each sample analysed in FTIR spectroscopy. A successful milk species (cow, sheep, and water buffalo) discrimination and classification were achieved utilising Hierarchical cluster and principle component analyses (PCA) on the basis of Euclidean distance and Ward's algorithm. Amide-I (1700-1600/cm) and Amide-II (1565-1520/cm) spectral bands were used in the chemometric method. The results of the study indicated that adulteration of milk samples can be quantitatively detected by the FTIR technique in a short time with high accuracy. In conclusion, this method could be used as a new alternative technique for routine analysis in authenticity control of milk species origin. PMID- 29785907 TI - The fatty acid composition of Estonian and Latvian retail milk; implications for human nutrition compared with a designer milk. AB - The study reported in this Research Communication compared retail milks' FA profiles from two neighbouring countries, estimated the potential contributions of these milks and a designer milk (achieved by changing the diet of the dairy cow) to the recommended human dietary intake of FA, and predicted (based on the milk FA profile) methane emission from dairy cows. Retail milks in Estonia and Latvia were purchased from supermarkets monthly for one year. To compare the FA composition of retail milk with designer milk with an increased PUFA content, the bulk milk FA profile from a separate field trial was used. Milk FA concentrations of the two neighbouring countries were affected by state, season and their interaction, while the main influence on all these factors were different feeding practices (grazing availability, forage to concentrate ratio and legume-rich silages vs. maize silages). Three cups (600 mL; fat content 2.5 g/100 g) of Estonian, or Latvian retail milk or designer milk per day contributed more to the recommended intakes of saturated FA (SFA) (42.5, 42.7, 38.7%, respectively) than other FA. Compared to the retail milks, alpha-linolenic acid estimated intake was almost doubled by designer milk consumption (19.7% of adequate intake) without influencing summed intakes of SFA and trans FA. There were state and seasonal differences in the predicted methane outputs of dairy cattle based on retail milk FA. Although the FA profiles of retail milks in the two neighbouring countries were affected by state and season, an appreciable increase in human dietary intakes of beneficial fatty acids from milk, and concomitant reduction in methane emissions from dairy cows, can be achieved only by targeted feeding. PMID- 29785909 TI - Udder skin surface temperature variation pre- and post- milking in dairy cows as determined by infrared thermography. AB - The objectives of the research reported in this Research Communication were to compare the variation of hind quarter skin surface temperature pre- and post- milking in dairy cows and to determine the optimal time to capture images by infrared thermography for improving the sensitivity and specificity of mastitis detection in dairy cows. Hind quarter infrared images of 102 Holstein dairy cows were captured from the caudal view by an infrared camera pre-milking and post milking. The udder skin surface temperature was measured with the help of the image processing software. No significant difference was found between the left and right quarter skin surface temperature pre- and post- milking. The hind quarter skin surface temperature pre-milking was not significantly influenced by milk yield, but exhibited a rising trend along with the increase of milk yield. The hind quarter skin surface temperature post-milking was significantly influenced by milk yield. This leads us to conclude that the sensitivity and specificity of IRT in mastitis detection may be influenced by milk yield and it may be better to capture the infrared images of cow udders pre-milking. PMID- 29785910 TI - A large-scale study of indicators of sub-clinical mastitis in dairy cattle by attribute weighting analysis of milk composition features: highlighting the predictive power of lactose and electrical conductivity. AB - Sub-clinical mastitis (SCM) affects milk composition. In this study, we hypothesise that large-scale mining of milk composition features by pattern recognition models can identify the best predictors of SCM within the milk composition features. To this end, using data mining algorithms, we conducted a large-scale and longitudinal study to evaluate the ability of various milk production parameters as indicators of SCM. SCM is the most prevalent disease of dairy cattle, causing substantial economic loss for the dairy industry. Developing new techniques to diagnose SCM in its early stages improves herd health and is of great importance. Test-day Somatic Cell Count (SCC) is the most common indicator of SCM and the primary mastitis surveillance approach worldwide. However, test-day SCC fluctuates widely between days, causing major concerns for its reliability. Consequently, there would be great benefit to identifying additional efficient indicators from large-scale and longitudinal studies. With this intent, data was collected at every milking (twice per day) for a period of 2 months from a single farm using in-line electronic equipment (346 248 records in total). The following data were analysed: milk volume, protein concentration, lactose concentration, electrical conductivity (EC), milking time and peak flow. Three SCC cut-offs were used to estimate the prevalence of SCM: Australian >= 250 000 cells/ml, European >=200 000 cells/ml and New Zealand >= 150 000 cells/ml. At first, 10 different Attribute Weighting Algorithms (AWM) were applied to the data. In the absence of SCC, lactose concentration featured as the most important variable, followed by EC. For the first time, using attribute weighted modelling, we showed that the concentration of lactose in milk can be used as a strong indicator of SCM. The development of machine-learning expert systems using two or more milk variables (such as lactose concentration and EC) may produce a predictive pattern for early SCM detection. PMID- 29785911 TI - Characterisation of mango flavoured curd powder developed using spray drying technique. AB - This research communication describes the production of flavoured (Mango) curd powder. The mango flavoured curd powder was developed in two different temperatures (150 degrees C and 170 degrees C) in various ratios with one control curd sample. The final powder was obtained in high quality which can be used directly or as an ingredient. The percentage of lactic acid in the developed powder showed the healthy amount of probiotic present in it. The physical properties and probiotic growth of the mango flavoured curd powder, developed by spray drying technique, have been evaluated in this article. Various properties were analysed, including moisture content, water activity, dispersibility, bulk and tapped density, porosity, particle morphology, colour analysis, pH, functional group identification using FTIR, identification of the pure culture and % of lactic acid for 3 different Curd and Mango ratios (1:0.5, 1:1, 0.5:1), respectively with one control curd sample. The lactobacillus strain found in this newly developed flavoured powder was Lactobacillus curieae. Lactic acid percentage showed the powder to contain appropriate and healthy amount of probiotic and significant flavour. Future studies are focused on storage studies of the produced powder. PMID- 29785912 TI - Para-kappa-casein during the ripening and storage of low-pH, high-moisture Feta cheese. AB - The hypothesis of this research paper was that the physicochemical conditions in a low-pH, high-moisture white brined cheese such as Feta would make para-kappa casein vulnerable to residual chymosin activity during ripening and storage. It was important to address this hypothesis, since cheese para-kappa-casein could theoretically be used for the assessment of the origin of cheese milk by means of various analytical methods. Feta cheese was manufactured from sheep milk and from four different mixtures of sheep and goat milk in triplicate. The para-kappa casein of Feta samples taken during 120 d of ripening and storage was estimated by means of cation-exchange HPLC and proteolysis was determined in terms of free amino groups. Despite their similarity, sheep and goat para-kappa-casein were efficiently separated and the changes of their chromatographic areas indicated that hydrolysis took place during the first stage of ripening. In accordance to the evolution of free amino groups, para-kappa-caseins remained stable thereafter. The hydrolysis pattern was not affected by the composition of the cheese milk mixture and after 120 d at least two thirds of the initial quantity remained intact. Considering the efficient separation of sheep and goat para kappa-caseins and their stability during Feta storage, the same method was used for the evaluation of the percentage of goat milk in the cheese milk. The actual and the estimated percentage of goat milk within the range 0-40 were strongly correlated (R = 0.997, n = 60) and the standard error of estimation was 0.914. PMID- 29785913 TI - Editorial: Watering holes. PMID- 29785914 TI - Fermented camel milk prevents carbon tetrachloride induced acute injury in kidney of mice. AB - Fermented milk is known to possess potent antioxidant activity. The present study was undertaken to assess the preventive effect of fermented camel milk (FCM) prepared using lactococcus lactis subsp. cremoris against CCl4 induced kidney damage in mice. Nephrotoxicity was induced in mice by a single dose of CCl4 (10 ml/kg 0.3% olive oil, ip). Female mice were pretreated daily with FCM for 15 d. Renal damage was associated with an increase in oxidative stress parameters (lipid peroxidation, protein carbonyl and changes in antioxidant enzyme activities and non-enzymatic antioxidant) and nephropathology markers.The renal injury induced by CCl4 was confirmed by the histological study of the CCl4 intoxicated mice. Pretreatment with FCM significantly prevented renal dysfunction by reducing oxidative stress, while mice recovered normal kidney histology. Moreover, FCM prevented toxicity biomarker changes by reducing creatinine, urea, uric acid, lactate dehydrogenase (LDH) and electrolytes levels in plasma. These data indicate that FCM is efficient in inhibiting oxidative stress induced by CCl4, and suggests that the administration of this milk may be helpful in the prevention of kidney damage. PMID- 29785915 TI - The effects of a synthetic analogue of the Bovine Appeasing Pheromone on milk yield and composition in Valdostana dairy cows during the move from winter housing to confined lowland pastures. AB - This Research Communication describes the effects of a synthetic analogue of the Bovine Appeasing Pheromone (BAP) on milk parameters in Valdostana dairy cows during the first turning out from tie-stalls to confined lowland pastures around the farms. Thirty healthy lactating Valdostana cows were enroled in the study and randomly divided into 2 groups: experimental group (EG, n = 15) and control group (CG, n = 15). The two groups were separately housed in the same farm and managed outside in two different pens. Treatment (BAP and solution) and control (solution only) were poured on the nuchal skin area between the horns when the animals were inside the farm at the feeding rack every 7 d for 28 d (T0-T4). Milk samples were evaluated at the same time points (T0-T4). Daily milk production (kg/day) was higher in the EG than in the CG, particularly during the first day after the turning out to pasture (T1). Somatic Cell Count (103 cells/ml) was higher in the placebo group than in the EG, especially at T1. Proteins, fat, fat-free dry matter and casein (g/100 g) were not affected by the treatment. In T1 urea (mg/dl) content was higher in CG vs. EG, suggesting a more correct metabolic balance in the group treated with BAP. The use of BAP appears to modulate adaptation in ways that may improve dairy cow performance in the context of changes in management routines. PMID- 29785916 TI - Focusing on fatty acid profile in milk from different species after in vitro digestion. AB - We report the fatty acid profile of raw milk and of the corresponding digested milk from different sources (human milk, formula milk and donkey, bovine, ovine and caprine milk) to gain information on the nutritional quality of different milk sources in infant nutrition.Short chain fatty acids (SC-FA) were higher in bovine and caprine milk, intermediate in ovine and donkey and lower in human and formula milk. Medium chain fatty acids (MC-FA) showed the highest values for bovine and caprine milk and the lowest for donkey and formula milk, whereas long chain fatty acids (LC-FA) were the highest in donkey and formula milk and intermediate in human milk.The percentage distribution of fatty acids liberated after in vitro digestion did not reflect the patterns found in the corresponding milk sources. In particular, MC free fatty acids (MC-FFA) showed the highest and the lowest values in donkey and in formula milk, LC-FFA showed the highest value in human milk. The total FFA was highest in human milk, lowest in formula milk and intermediate in donkey, bovine, ovine, and caprine milk. PMID- 29785917 TI - Effect of season and breed on physiological and blood parameters in buffaloes. AB - In this Research Communication we describe the effect of temperature and humidity index (THI) on various physiological traits, the plasma heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and cortisol levels and other blood parameters in crossbred buffalo (Nili-Ravi * Murrah) and Mediterranean buffalo to compare their tolerance to heat stress. As expected, crossbred buffalo had a significantly higher rectal temperature (RT), body surface temperature (BT), respiratory rate (RR), HSP70 and HSP90 levels in summer compared to spring and winter. RT and BT were also significantly higher in spring compared to winter. A significant correlation existed between THI and RT (r = 0.81) and RR (r = 0.84). Importantly, in summer the crossbred buffalo had a significantly lower RT, BT and RR and higher HSP70, HSP90 and cortisol levels than the Mediterranean buffalo. In conclusion, higher THI was associated with significant increase in RT, RR, BT, HSP70, HSP90 and cortisol levels, and the crossbred buffalo were more heat tolerant than Mediterranean buffalo. PMID- 29785918 TI - Proteomic analysis of the effects of lutein on mammary gland metabolism in dairy cows. AB - The aim of the research reported in this Research Communication was to identify differentially expressed proteins in dairy cows with normal and lutein diet and to elucidate the mechanisms of lutein-induced effects on bovine mammary gland metabolism using a comparative proteomic approach. Thirty-three differentially expressed proteins were identified from mammary gland of control diet-fed and lutein diet-fed dairy cows. Among these proteins, 15 were upregulated and 18 were downregulated in the lutein group. Functional analysis of the differentially expressed proteins showed that increased blood flow, depressed glycolysis, enhanced lactose anabolism, decreased fatty acid oxidation and up-regulated beta lactoglobulin expression were connected with lutein addition. These results suggested that the increased blood flow, reduced glucose catabolism, enhanced capacity for milk lactose synthesis, depressed fatty acid catabolism and increased expression of antioxidantion related protein may be the prime factors contributing to the increased milk production and enhanced immune status in lutein-fed dairy cows. This study provides molecular mechanism of dietary lutein in regulating lactation of dairy cows. PMID- 29785919 TI - Genomic selection in dairy cattle simulated populations. AB - Genomic selection is arguably the most promising tool for improving genetic gain in domestic animals to emerge in the last few decades, but is an expensive process. The aim of this study was to evaluate the economic impact related to the implementation of genomic selection in a simulated dairy cattle population. The software QMSim was used to simulate genomic and phenotypic data. The simulated genome contained 30 chromosomes with 100 cm each, 1666 SNPs markers equally spread and 266 QTLs randomly designated for each chromosome. The numbers of markers and QTLs were designated according to information available from Animal QTL (http://www.animalgenome.org/QTLdb) and Bovine QTL (http://bovineqtl.tamu.edu/). The allelic frequency changes were assigned in a gamma distribution with alpha parameters equal to 0.4. Recurrent mutation rates of 1.0e-4 were assumed to apply to markers and QTLs. A historic population of 1000 individuals was generated and the total number of animals was reduced gradually along 850 generations until we obtained a number of 200 animals in the last generation, characterizing a bottleneck effect. Progenies were created along generations from random mating of the male and female gametes, assuming the same proportion of both genders. Than the population was extended for another 150 generations until we obtained 17 000 animals, with only 320 male individuals in the last generation. After this period a 25 year of selection was simulated taking into account a trait limited by sex with heritability of 0.30 (i.e. milk yield), one progeny/cow/year and variance equal to 1.0. Annually, 320 bulls were mated with 16 000 dams, assuming a replacement rate of 60 and 40% for males and females, respectively. Selection and discard criteria were based in four strategies to obtain the EBVs assuming as breeding objective to maximize milk yield. The progeny replaced the discarded animals creating an overlapping generation structure. The selection strategies were: RS is selection based on random values; PS is selection based on phenotypic values; Blup is selection based on EBVs estimated by BLUP; and GEBV is selection based on genomic estimated breeding values in one step, using high (GBlup) and low (GBlupi) density panels. Results indicated that the genetic evaluation using the aid of genomic information could provide better genetic gain rates in dairy cattle breeding programs as well as reduce the average inbreeding coefficient in the population. The economic viability indicators showed that only Blup and GBlup/GBlupi strategies, the ones that used milk control and genetic evaluation were economic viable, considering a discount rate of 6.32% per year. PMID- 29785920 TI - Effects of herd and physiological status on variation of 16 immunological and inflammatory parameters in dairy cows during drying off and the transition period. AB - During drying off and transition period, cows are subject to changes in endocrine status, metabolic stressors and altered immune functions, which could lead to an increased risk of disease. To expand our knowledge on the immune/inflammatory status and to identify markers to define cow status during this interval, the pattern of 9 different cellular parameters, 5 cytokines, 2 enzymes and 3 cellular ratios in blood samples were assessed in 15 primiparous cows belonging to three different dairy herds in Lombardy. Our data showed that the variation of almost all parameters was influenced by the physiological period in which the samples were collected, except for apoptosis, IL-1beta, IL-6, lysozyme and granulocyte/monocyte ratio. Several markers were directly correlated either to the herd alone (IL-1beta, IL-6, lysozyme, granulocyte/lymphocyte ratio and granulocyte/monocyte ratio) or in association with the sampling time (white blood cell count, necrosis, lymphocytes count, CD4+ lymphocytes proportion). Hierarchical cluster analysis identified three herd-associated sample clusters showing different frequency along the follow-up period. The results of this field study highlight the importance of the herd factor in the immune/inflammatory response. Furthermore, these results suggest that cellular parameters are probably the most suitable markers to define cow status during drying-off and the peripartum period. PMID- 29785921 TI - Case Report: Successful Treatment of Chromoblastomycosis Caused by Fonsecaea monophora in a Patient with Psoriasis Using Itraconazole and Acitretin. AB - Chromoblastomycosis is a worldwide chronic subcutaneous infection caused by dematiaceous fungi and clinically characterized by verrucous lesions. Herein, we report a rare case of chromoblastomycosis caused by Fonsecaea monophora in a 60 year-old male carpenter with a 40-year history of psoriasis from Shandong in northern China. A fungal infection coexisting with psoriasis presents a management dilemma. Our patient responded well to combined itraconazole and acitretin therapy and the lesions resolved completely after 1 month of treatment. PMID- 29785922 TI - Karyotype Evolution of Chagas Disease Vectors (Hemiptera, Triatominae). AB - The Triatominae subfamily is composed of 153 hematophagous species that are potential vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Karyotypic studies in triatomines were initiated in 1909. There are 92 karyotypes described, all grouped into the tribes Rhodniini and Triatomini. Recently, a phylogenetic study of the triatomines that combines molecular data with geological changes was performed. We now discuss how the karyotype evolved with the diversification of the triatomines. PMID- 29785923 TI - Cholera Outbreak due to Raw Seafood Consumption in South Korea, 2016. AB - Three cases of cholera occurred in South Korea during a period of three weeks in August 2016. All the cases were associated with the consumption of raw seafood in southern coastal area of South Korea. Epidemiologic investigations were performed to track the spread of cholera, including persons in contact with the cholera patients, seafood, and seawater from the fish tank and marine environments. A microbiological investigation demonstrated that cholera isolated from the three patients and a seawater sample at the Korea Strait showed identical serotype (O1 Ogawa), biotype (El tor), and toxin (ctx-positive). Pulsed-field gel electrophoresis analysis showed that the three clinical strains are identical (100%) and shared 97% identity with the seawater sample. PMID- 29785924 TI - Preliminary Evidence for the Absence of Cystic Echinococcosis in Gabon: A Cross Sectional Pilot Survey in Humans and Definitive Hosts. AB - Cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and polymerase chain reaction (PCR) amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role. PMID- 29785925 TI - Comparison of Two Genotyping Methods for Distinguishing Recrudescence from Reinfection in Antimalarial Drug Efficacy/Effectiveness Trials. AB - Genotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 (msp-1 and msp-2), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher's exact test; P = 0.887 and P = 0.768, respectively). There was a strong agreement between the two methods in predicting treatment outcomes and resolving the genetic complexity of malaria infections in this setting. These results support the use of this SNP assay as an alternative method for correcting antimalarial efficacy/effectiveness data. PMID- 29785926 TI - Intramedullary nail fixation versus locking plate fixation for adults with a fracture of the distal tibia: the UK FixDT RCT. AB - BACKGROUND: The best treatment for fractures of the distal tibia remains controversial. Most of these fractures require surgical fixation, but the outcomes are unpredictable and complications are common. OBJECTIVES: To assess disability, quality of life, complications and resource use in patients treated with intramedullary (IM) nail fixation versus locking plate fixation in the 12 months following a fracture of the distal tibia. DESIGN: This was a multicentre randomised trial. SETTING: The trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017. PARTICIPANTS: In total, 321 adult patients were recruited. Participants were excluded if they had open fractures, fractures involving the ankle joint, contraindication to nailing or inability to complete questionnaires. INTERVENTIONS: IM nail fixation (n = 161), in which a metal rod is inserted into the hollow centre of the tibia, versus locking plate fixation (n = 160), in which a plate is attached to the surface of the tibia with fixed-angle screws. MAIN OUTCOME MEASURES: The primary outcome measure was the Disability Rating Index (DRI) score, which ranges from 0 points (no disability) to 100 points (complete disability), at 6 months with a minimum clinically important difference of 8 points. The DRI score was also collected at 3 and 12 months. The secondary outcomes were the Olerud-Molander Ankle Score (OMAS), quality of life as measured using EuroQol-5 Dimensions (EQ-5D), complications such as infection, and further surgery. Resource use was collected to inform the health economic evaluation. RESULTS: Participants had a mean age of 45 years (standard deviation 16.2 years), were predominantly male (61%, 197/321) and had experienced traumatic injury after a fall (69%, 223/321). There was no statistically significant difference in DRI score at 6 months [IM nail fixation group, mean 29.8 points, 95% confidence interval (CI) 26.1 to 33.7 points; locking plate group, mean 33.8 points, 95% CI 29.7 to 37.9 points; adjusted difference, 4.0 points, 95% CI -1.0 to 9.0 points; p = 0.11]. There was a statistically significant difference in DRI score at 3 months in favour of IM nail fixation (IM nail fixation group, mean 44.2 points, 95% CI 40.8 to 47.6 points; locking plate group, mean 52.6 points, 95% CI 49.3 to 55.9 points; adjusted difference 8.8 points, 95% CI 4.3 to 13.2 points; p < 0.001), but not at 12 months (IM nail fixation group, mean 23.1 points, 95% CI 18.9 to 27.2 points; locking plate group, 24.0 points, 95% CI 19.7 to 28.3 points; adjusted difference 1.9 points, 95% CI -3.2 to 6.9 points; p = 0.47). Secondary outcomes showed the same pattern, including a statistically significant difference in mean OMAS and EQ-5D scores at 3 and 6 months in favour of IM nail fixation. There were no statistically significant differences in complications, including the number of postoperative infections (13% in the locking plate group and 9% in the IM nail fixation group). Further surgery was more common in the locking plate group (12% in locking plate group and 8% in IM nail fixation group at 12 months). The economic evaluation showed that IM nail fixation provided a slightly higher quality of life in the 12 months after injury and at lower cost and, therefore, it was cost-effective compared with locking plate fixation. The probability of cost-effectiveness for IM nail fixation exceeded 90%, regardless of the value of the cost-effectiveness threshold. LIMITATIONS: As wound dressings after surgery are clearly visible, it was not possible to blind the patients to their treatment allocation. This evidence does not apply to intra-articular (pilon) fractures of the distal tibia. CONCLUSIONS: Among adults with an acute fracture of the distal tibia who were randomised to IM nail fixation or locking plate fixation, there were similar disability ratings at 6 months. However, recovery across all outcomes was faster in the IM nail fixation group and costs were lower. FUTURE WORK: The potential benefit of IM nail fixation in several other fractures requires investigation. Research is also required into the role of adjuvant treatment and different rehabilitation strategies to accelerate recovery following a fracture of the tibia and other long-bone fractures in the lower limb. The patients in this trial will remain in longer-term follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99771224 and UKCRN 13761. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 25. See the NIHR Journals Library website for further project information. PMID- 29785927 TI - PRECICE(r) magnetically-driven, telescopic, intramedullary lengthening nail: pre clinical testing and first 30 patients. AB - INTRODUCTION: Femoral/tibial lengthening with a telescopic, magnetically-powered, intramedullary nail is an alternative to lengthening with external fixation. METHODS: Pre-clinical testing was conducted of the PRECICE in a human cadaver. A retrospective review of the first 30 consecutive patients who underwent unilateral lengthening was also conducted. Nail accuracy was obtained by comparing the amount of nail distraction to the final bone length achieved at the end of the distraction process. Relative standard deviation of accuracy was used to calculate nail precision. RESULTS: Devices performed successfully in a human cadaver. Thirty consecutive patients (10 females, 20 males; mean age, 23 years) with limb length discrepancy (LLD) were followed an average of 19 months (range, 12-24 months). Etiology included congenital shortening (14), posttraumatic deformities (7), Ollier disease (3), osteosarcoma resection (1), prior clubfoot (2), hip dysplasia (1), post-septic growth arrest of knee (1), and LLD after hip arthroplasty (1). Twenty-four femoral and eight tibial nails were implanted. Mean preoperative lengthening goal was 4.4 cm (range, 2-6.5 cm); mean postoperative length achieved was 4.3 cm (range, 1.5-6.5 cm). Average consolidation index was 36.4 days/cm (range, 12.8-113 days/cm). Mean nail accuracy was 97.3% with a precision of 92.4%. Average preoperative and 12-month postoperative Enneking scores were 21.5 and 25.3 (p < 0.001), respectively. The preoperative and 12 month postoperative SF-12 physical and mental component scores were not statistically different. Nine complications (nine limb segments) resolved: two partial femoral unions, two suspected deep vein thrombosis (DVT), one delayed tibial union, one fibular nonunion, one peroneal nerve irritation, one knee joint subluxation, and one confirmed DVT. Twenty-nine (91%) of 32 limb segments achieved successful bone healing without revision surgery. DISCUSSION: Limb lengthening with PRECICE is reliable, but larger trials with longer follow-up will reveal limitations. Implantable nails prevent problems associated with external fixation, such as muscle tethering and pin-site infections. PMID- 29785928 TI - Post-decision biases reveal a self-consistency principle in perceptual inference. AB - Making a categorical judgment can systematically bias our subsequent perception of the world. We show that these biases are well explained by a self-consistent Bayesian observer whose perceptual inference process is causally conditioned on the preceding choice. We quantitatively validated the model and its key assumptions with a targeted set of three psychophysical experiments, focusing on a task sequence where subjects first had to make a categorical orientation judgment before estimating the actual orientation of a visual stimulus. Subjects exhibited a high degree of consistency between categorical judgment and estimate, which is difficult to reconcile with alternative models in the face of late, memory related noise. The observed bias patterns resemble the well-known changes in subjective preferences associated with cognitive dissonance, which suggests that the brain's inference processes may be governed by a universal self consistency constraint that avoids entertaining 'dissonant' interpretations of the evidence. PMID- 29785929 TI - Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii. AB - Most eukaryotic parasites are obligately heteroxenous, requiring sequential infection of different host species in order to survive. Toxoplasma gondii is a rare exception to this rule, having a uniquely facultative heteroxenous life cycle. To understand the origins of this phenomenon, we compared development and stress responses in T. gondii to those of its its obligately heteroxenous relative, Hammondia hammondi and have identified multiple H. hammondi growth states that are distinct from those in T. gondii. Of these, the most dramatic difference was that H. hammondi was refractory to stressors that robustly induce cyst formation in T. gondii, and this was reflected most dramatically in its unchanging transcriptome after stress exposure. We also found that H. hammondi could be propagated in vitro for up to 8 days post-excystation, and we exploited this to generate the first ever transgenic H. hammondi line. Overall our data show that H. hammondi zoites grow as stringently regulated, unique life stages that are distinct from T. gondii tachyzoites, and implicate stress sensitivity as a potential developmental innovation that increased the flexibility of the T. gondii life cycle. PMID- 29785931 TI - First bone-cracking dog coprolites provide new insight into bone consumption in Borophagus and their unique ecological niche. AB - Borophagine canids have long been hypothesized to be North American ecological 'avatars' of living hyenas in Africa and Asia, but direct fossil evidence of hyena-like bone consumption is hitherto unknown. We report rare coprolites (fossilized feces) of Borophagus parvus from the late Miocene of California and, for the first time, describe unambiguous evidence that these predatory canids ingested large amounts of bone. Surface morphology, micro-CT analyses, and contextual information reveal (1) droppings in concentrations signifying scent marking behavior, similar to latrines used by living social carnivorans; (2) routine consumption of skeletons; (3) undissolved bones inside coprolites indicating gastrointestinal similarity to modern striped and brown hyenas; (4) B. parvus body weight of ~24 kg, reaching sizes of obligatory large-prey hunters; and (5) prey size ranging ~35-100 kg. This combination of traits suggests that bone-crushing Borophagus potentially hunted in collaborative social groups and occupied a niche no longer present in North American ecosystems. PMID- 29785932 TI - Cortical thickness correlates of minor neurological signs in patients with first episode psychosis. AB - Neurological soft signs (NSS) are subtle abnormalities of motor and sensory function that are present in the absence of localized brain pathological lesions. In psychoses they have been consistently associated with a distinct pattern of cortical and subcortical brain structural alterations at the level of the heteromodal cortex and basal ganglia. However, a more specific and accurate evaluation of the cytoarchitecture of the cortical mantle could further advance our understanding of the neurobiological substrate of psychosis. We investigated the relationship between brain structure and NSS in a sample of 66 patients at their first episode of psychosis. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and Freesurfer to explore cortical thickness and surface area. Higher rates of NSS were associated with a reduction of cortical thickness in the precentral and postcentral gyri, inferior parietal, superior temporal, and fusiform gyri. Higher rates of NSS were also associated with smaller surface areas of superior temporal gyrus and frontal regions (including middle frontal, superior and orbito-frontal gyri). Finally, more sensory integration signs were also associated with larger surface area of the latero-occipital region. We conclude that the presence of NSS in psychosis is associated with distinct but widespread changes in cortical thickness and surface area, in areas crucial for sensory-motor integration and for the fluid execution of movement. Studying these morphological correlates with advanced neuroimaging techniques can continue to improve our knowledge on the neurobiological substrate of these important functional correlates of psychosis. PMID- 29785930 TI - Shearing in flow environment promotes evolution of social behavior in microbial populations. AB - How producers of public goods persist in microbial communities is a major question in evolutionary biology. Cooperation is evolutionarily unstable, since cheating strains can reproduce quicker and take over. Spatial structure has been shown to be a robust mechanism for the evolution of cooperation. Here we study how spatial assortment might emerge from native dynamics and show that fluid flow shear promotes cooperative behavior. Social structures arise naturally from our advection-diffusion-reaction model as self-reproducing Turing patterns. We computationally study the effects of fluid advection on these patterns as a mechanism to enable or enhance social behavior. Our central finding is that flow shear enables and promotes social behavior in microbes by increasing the group fragmentation rate and thereby limiting the spread of cheating strains. Regions of the flow domain with higher shear admit high cooperativity and large population density, whereas low shear regions are devoid of life due to opportunistic mutations. PMID- 29785933 TI - A Comparison of Peripheral Imaging Technologies for Bone and Muscle Quantification: A Review of Segmentation Techniques. AB - Musculoskeletal science has developed many overlapping branches, necessitating specialists from 1 area of focus to often require the expertise in others. In terms of imaging, this means obtaining a comprehensive illustration of bone, muscle, and fat tissues. There is currently a lack of a reliable resource for end users to learn about these tissues' imaging and quantification techniques together. An improved understanding of these tissues has been an important progression toward better prediction of disease outcomes and better elucidation of their interaction with frailty, aging, and metabolic disorders. Over the last decade, there have been major advances into the image acquisition and segmentation of bone, muscle, and fat features using computed tomography (CT), magnetic resonance imaging (MRI), and peripheral modules of these systems. Dedicated peripheral quantitative musculoskeletal imaging systems have paved the way for mobile research units, lower cost clinical research facilities, and improved resolution per unit cost paid. The purpose of this review was to detail the segmentation techniques available for each of these peripheral CT and MRI modalities and to describe advances in segmentation methods as applied to study longitudinal changes and treatment-related dynamics. Although the peripheral CT units described herein have established feasible standardized protocols that users have adopted globally, there remain challenges in standardizing MRI protocols for bone and muscle imaging. PMID- 29785934 TI - Imaging Modalities in the Etiologic Evaluation of Unilateral Vocal Fold Paralysis. AB - OBJECTIVE: This study aimed to investigate the roles of computed tomography (CT) and neck ultrasonography (US) in evaluating unilateral vocal fold paralysis (UVFP) of unknown etiology and to compare our results with those of other studies to assess the differences in etiology of UVFP. METHODS: We investigated the medical records of 202 eligible patients with UVFP. In total, 168 underwent chest CT, 118 underwent neck CT, and 108 underwent head CT. One hundred and three patients were also evaluated with high-resolution neck US. The etiologic causes of UVFP were also determined. RESULTS: Of the 202 eligible patients, the occult cause of the UVFP was determined in 96 patients (47.5%). Idiopathic causes were the most common etiologies (n = 106). In occult causes group, chest lesions were the most common diseases causing paralysis (52 cases) and included lung cancer (n = 28) and mediastinal malignancy (n = 8). More than half of the neck lesions were of thyroid origin. Of the 18 thyroid lesions, 12 were thyroid malignancies. Chest CT had an intermediate yield of 30.9% (52 of 168). Neck US had a diagnostic yield close to that of neck CT (26.2%). CONCLUSION: UVFP may result mainly from idiopathic, lung cancer, mediastinal, and thyroid malignancies. The initial use of neck US as an alternative to CT may be advocated for the determination of diseases resulting in UVFP. PMID- 29785935 TI - The Impact of Dysphonic Voices on Children's Comprehension of Spoken Language. AB - BACKGROUND: This study investigated the effect of teachers' dysphonic voices on children's listening comprehension. METHODS: One hundred thirty-four grade three and four students were recruited from local primary schools in Hong Kong. They were required to listen to six passages, three in Cantonese and three in English, which were either read in normal, mildly dysphonic, or severely dysphonic voices. The students were required to complete six multiple-choice comprehension questions upon listening to each passage. Comprehension performance across languages, dysphonic severities, genders, and question types were examined. RESULTS: The results showed that listening comprehension was significantly poorer even when speaker's voice quality was mildly impaired. Performance in Cantonese was generally better than that in English but no significant difference in the pattern of decline was found. Both boys and girls suffered to similar extent under dysphonic situations. Differences in performance in various question types were discussed. CONCLUSIONS: These findings support the urgent need to implement voice care education for the teaching profession. PMID- 29785936 TI - An Objective Parameter to Classify Voice Signals Based on Variation in Energy Distribution. AB - OBJECTIVES: The purpose of this paper is to introduce an iterative nonlinear weighted method based on the variation in spectral energy distribution present in a voice signal to differentiate between four voice types: type 1 voice signals are nearly periodic, type 2 voice signals have strong modulations and subharmonics, type 3 signals are chaotic, and type 4 signals are dominated by stochastic noise. STUDY DESIGN: A total of 135 voice signal samples of the sustained vowel /a/ were obtained from the Disordered Voice Database and then individually categorized into the appropriate voice types based on the classification system described in Sprecher et al (2010). Voice samples were analyzed using the nonlinear methods of spectrum convergence ratio, rate of divergence, and nonlinear energy difference ratio (NEDR) to investigate classifier efficacy. METHODS: An iterative nonlinear weighted method based on the derivative of instantaneous frequency and Fourier transformations is applied to calculate spectral energy distributions. The distribution is then used to calculate the NEDR to classify voice signal types. RESULTS: Statistical analysis revealed that NEDR effectively differentiated between all four voice types (P < 0.001). Subsequent multiclass receiver operating characteristic analysis demonstrated that NEDR (area under the curve [95% CI] = 0.99 [0.96-1.0]) possessed the greatest classification accuracy relative to spectrum convergence ratio and rate of divergence. CONCLUSION: NEDR was shown to be an effective metric for objective differentiation between all four voice signal types. NEDR calculations occurred approximately instantaneously, constituting a substantial improvement over the tedious computational time required for calculation of previous nonlinear parameters. This metric could assist clinicians in the diagnosis of voice disorders and monitor the efficacy of treatment through observation of voice acoustical improvement over time. PMID- 29785937 TI - The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts. AB - BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme alpha galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL 3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage. PMID- 29785938 TI - Decision-making in end of life care. Are we really playing together in the same team? AB - BACKGROUND: Limitation of life-sustaining treatment is increasingly common in critical care units, and controlled donation after circulatory death is starting to be included as an option within patient care plans. Lack of knowledge and misunderstandings can place a barrier between healthcare professionals. OBJECTIVE: To determine the perceptions, knowledge and attitudes of physicians and nurses working in intensive care units regarding Limitation of life sustaining treatment and controlled donation after circulatory death. DESIGN, SETTINGS AND PARTICIPANTS: Cross-sectional study carried out in 13 Spanish hospitals by means of an ad hoc questionnaire. METHODS: Contingency tables, Pearson's chi-squared test, Student's t-test and the Mann-Whitney u-test were used to carry out descriptive, bivariate and multivariate statistical analyses of responses. RESULTS: Although Limitation of life-sustaining treatment is a widespread practice, the survey revealed that nurses feel excluded from the development of protocols and the decision-making process, whilst the perception of physicians is that they have greater knowledge of the topic, and decisions are reached in consensus. CONCLUSIONS: Multi-disciplinary training programmes can help critical healthcare providers to work together with greater coordination, thus benefitting patients and their next of kin by providing excellent end-of life care. PMID- 29785939 TI - Exploring an Integrative Patient-Tailored Complementary Medicine Approach for Chemotherapy-Induced Taste Disorders. AB - CONTEXT: Chemotherapy-induced taste disorder (CITD) is a common adverse effect among patients with cancer, with no effective known treatment. OBJECTIVES: Exploring the impact of a patient-tailored complementary and integrative medicine (CIM) treatment program on CITD-related severity. DESIGN: Prospective study on patients' chart. SETTING: Integrative oncology program operating within the Clalit Healthcare Oncology Service in northern Israel. PATIENTS: Patients were referred by their oncology healthcare practitioner to a consultation with a CIM trained integrative physician (IP). A patient-tailored CIM treatment program was designed, addressing quality of life (QOL)-related concerns which were evaluated using the Edmonton symptom assessment scale (ESAS) and the measure yourself concerns and well-being (MYCAW) questionnaires. RESULTS: A total of 626 patients were referred to the IP consultation, with CITD-related symptoms identified in 43, 34 of them returning for follow-up. The majority of patients treated with CIM reported a reduction in symptom severity (n = 29), with only three reporting no change, 2 an "unclear effect" and none a worsening of CITD-related symptoms. Acupuncture and herbal medicine (sage, carob, and wheatgrass juice, as mouthwash or applied to the oral mucosa) were the most frequently CIM modalities used. Assessment was considered optimal for 18 of the 29 patients who reported an improvement in ESAS scores for fatigue, drowsiness and depression. We conclude that a patient-tailored CIM program is a potentially effective and safe therapeutic option for CITD-related symptoms. Further research is needed in order to explore the impact of CIM treatments on taste and appetite-related concerns during chemotherapy. PMID- 29785940 TI - Metabolic effects, safety, and acceptability of very low-calorie ketogenic dietetic scheme on candidates for bariatric surgery. AB - BACKGROUND: Previous studies have demonstrated significant advantages from a preoperative dietetic regimen for candidates to bariatric procedure. OBJECTIVES: Evaluation of safety, efficacy, and acceptability of a very low-calorie ketogenic diet in patients before bariatric surgery. SETTING: University Hospital. METHODS: A standardized 30-day sequential preoperative diet regimen has been analyzed, optimizing metabolic response with gradual carbohydrate reintroduction. Patients were given a dedicated KetoStationkit, for use during the first 10 days of the scheme, followed by a hypocaloric scheme for 20 days. The study group underwent routine laboratory tests and anthropometric measurements (percent weight loss, body mass index, waist circumference) at enrollment (T0), after 10 days (T1), and after 30 days (T2). Ketone body levels were measured in the plasma and urine. RESULTS: Between January 2015 and September 2015, 119 patients were included in the study. Mean body mass index was 41.5 +/- 7.6 kg/m2. Weight, body mass index, and waist circumference at T0 and T1, T0 and T2, and T1 and T2 decreased significantly (P<.05). A bioelectrical impedance assay determined a significant reduction in visceral fat at T1 and T2. We observed a significant (P<.05) improvement in several clinical parameters, including glycemic and lipid profile parameters. We also observed a mean 30% reduction in liver volume. The majority of patients declared satisfied or very satisfied. The adverse effects were mild, of short duration, and not clinically relevant. CONCLUSION: Our results confirm the acceptability, safety, and significant advantage of a very low-calorie ketogenic diet for reducing weight and liver volume of patients in preparation for bariatric surgery. PMID- 29785941 TI - Life style and risk of atypical eating disorders in university students: Reality versus perception. AB - OBJECTIVE: The objectives of this paper were to determine weight status, eating, and alcohol drinking and smoking habits of university students, to determine the association between these variables with negative self-perception of their eating habits and to assess the risk of developing eating disorders. METHOD: A cross sectional study was carried out on 422 university students. The parameters analyzed were: nutritional status, eating habits, alcohol/ tobacco consumption, and risk of eating disorder. Logistic regression was applied to identify factors associated with a negative perception of eating habits. RESULTS: Out of the whole population that was analyzed, 5% were underweight, 16% overweight and 4% obese. Fifty-five percent of the sample analyzed did not consume five meals a day. The recommended foods for daily consumption were consumed below recommendations, while sausages/fatty meats, industrial pastries, lean meats, and fish were over consumed. Overall, the population perceived their eating habits as good/very good (63%). Alcohol and tobacco consumption predominated at weekends. The girls were more image-conscious (80.6% vs. 66%) and fearful of gaining weight (52.5% vs. 23.9%). Almost 30% had a distorted perception of body image. There was a 12.8% risk of atypical anorexia nervosa and 4.7% of atypical bulimia nervosa. CONCLUSIONS: College students led unhealthy lifestyles, mainly due to eating habits that do not conform to the establish recommendations. More than 17% are at risk of developing an atypical eating disorder. This information may be of interest in developing preventive actions. PMID- 29785942 TI - Experience in a community health service learning project in the development of final degree projects. PMID- 29785943 TI - [Roles and molecular mechanisms of hypoxia-inducible factors in renal cell carcinoma]. AB - Renal cancer is a common urologic malignancy. However, the therapeutic options for metastatic renal cancer patients are limited. Hypoxia (low oxygen) is a fundamental microenvironmental determinant of solid tumor pathophysiology. Recent data from molecular and clinical studies indicate that hypoxia-inducible factors (HIFs) play critical roles in the development and progress of renal cell carcinoma (RCC). The HIF transcription factor family is a type of heterodimeric transcription factor consisting of HIF-alpha and HIF-beta subunits and can transcriptionally activate genes that mediate the hypoxic response. In RCC, HIF 1alpha and HIF-2alpha have opposing effects: HIF-1alpha is a tumor suppressor while HIF-2alpha acts as an oncogene. In this review, we summarize the current advances in understanding the roles and molecular mechanisms of HIF signaling in RCC. We also discuss recent HIF-targeted strategies proposed to improve RCC treatment, which may provide a foundation for further research, including the development of precision medicine for the treatment of RCC. PMID- 29785944 TI - [Overview of the genetic control of horse coat color patterns]. AB - Mammalian coat color is one of the first phenotypic changes resulting from positive selection by humans, and it serves important roles in genetic and evolutionary processes. Among them, horses show a broad variety of coat color patterns, based on which it is difficult to distinguish the real phenotypes, resulting in confused records in horse breed registration. Thus, research in the genetic mechanisms on the development of coat color patterns is significant in horse reproduction and breeding. With the recent establishment of genomics and sequencing technologies, there are significant advances in research in the genetics of horse coat colors, which demonstrate that special coat colors could be associated with certain diseases. In this review, we classify horse coat colors from the perspective of genetics, and summarize the recent research progresses of the associated genes and molecular mechanisms on horse coat color development and its application, thereby providing references to further systematic research on horse coat color patterns and their practical uses in horse breeding. PMID- 29785945 TI - [The molecular mechanism of sheep seasonal breeding and artificial regulatory techniques for estrus and mating in anestrus]. AB - Seasonal breeding is an important factor limiting sheep production efficiency. Detailed analysis on the molecular mechanisms of seasonal breeding is the premise for improving estrus and mating rate of sheep during anestrus. Recent research showed that under long-photoperiod and short-photoperiod conditions, a series of changes in signaling molecules and cell morphology could be observed in ovine seasonal reproduction pathway. Based on the molecular mechanisms of seasonal reproduction, several technologies or methods for inducing estrus and mating of ewes in anestrus have been developed. In this review, photoperiod-induced changes in signaling molecules and cell morphology in pituitary and hypothalamic tissue are first summarized in terms of the molecular mechanisms and characteristics of seasonal reproduction. The application effect, advantages and disadvantages for applying these technologies for inducing estrus and mating of ewes in anestrus are then discussed, thereby providing the critical insights in identifying a new technology, which is environmentally friendly and efficient, to improve breeding rate in anestrus. PMID- 29785946 TI - [CRISPR/Cas systems in genome engineering of bacteriophages]. AB - Researches on CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated genes) systems, that are adaptive immunity systems encoded by prokaryotes, have promoted the development of new genome-editing tools. Bacteriophages are not only the driving elements for the evolution of prokaryotes' CRISPR arrays, but also the targets of the CRISPR/Cas systems. Studies on functional genomics of bacteriophages have been lagging behind the discovery of new phage strains and the sequencing of their genomes. CRISPR/Cas systems-driven genome engineering of bacteriophages provides a novel approach for bacteriophage functional genomics. This review comments on a few profound cases of genome engineering of bacteriophages that employed the CRISPR/Cas systems, and compares multiple procedures illustrating common or distinct features as well as advantages and disadvantages underlying each procedure. We design new applications of the CRISPR/Cas systems coupled with bacteriophage recombination systems, discuss their potential constraints, and offer suggestions for each option. PMID- 29785947 TI - [N-WASP regulates cortical neuron migration through its polyPro and VCA domains]. AB - Cortical neuron migration in the developing mouse forebrain is a complex process, which contains several steps related to cytoskeleton dynamics and remodeling. Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP-WAVE family, regulates actin cytoskeleton reorganization through the binding of its VCA domain to the Arp2/3 complex. Here we report expression patterns of N-WASP gene in the mouse developing embryonic cortex (E12.5~ E18.5) and find its expression levels are decreased during embryonic development. By using in utero electroporation (IUE) method, we find that either N-WASP overexpression or knockdown impairs cortical neuron migration, and the defects of cortical neuron migration caused by N-WASP overexpression are much more severe than that by its knockdown. N-WASP protein contains four domains: WH1, GBD, polyPro, and VCA. We generated a series of dominant negative N-WASP mutants by modifying these domains. Overexpression of N-WASP mutant lacking domain polyPro, VCA, or WH1, impairs cortical neuron migration. However, overexpression of N-WASP with the H208D point mutation, which abolishes the Cdc42 binding to N-WASP, causes only a marginal defect of cortical neuron migration. Finally, overexpression of the individual domain polyPro or VCA, but not WH1, can recapitulate the defects by N WASP overexpression. However, overexpression of WH1-GBD fragment has no apparent effect on cortical neuron migration. In conclusion, our data demonstrate that N WASP regulates cortical neuron migration mainly through its polyPro and VCA domains. PMID- 29785948 TI - [Genetics of fertility restoration in the isocytoplasm allonuclear C-group of cytoplasmic male sterility in maize]. AB - Maize is one of the first crops to produce hybrids using cytoplasmic male sterile lines. The C-type cytoplasmic male sterile (CMS-C) line is vital for hybrid seed production, and the fertility-restoration reaction along with its stability has a direct bearing on its applications. However, fertility restoration mechanism of CMS-C is complex and is still not clear so far. To further explore the factors affecting the fertility restoration of maize CMS, a series of test crosses were carried out by pollinating the isocytoplasm allonuclear CMS-C lines C48-2, Chuangzaosi and C478 with the test lines 18 bai, zi 330, 5022 and the restorer line A619, respectively. Four F2 populations and six double-cross combinations were obtained from the self-cross of fertility restored F1 and pollinating male sterility-maintained F1 with the male-fertility-restored F1, respectively. Meanwhile, we developed the incomplete diallel-cross combinations using the isocytoplasm allonuclear male sterile lines as maternal parents and their respective maintainer lines 48-2, huangzaosi and 478 as paternal parents. All the F1, F2 and double-cross populations were planted at distinct locations in different years, and the fertility-restoration reaction was scored by field investigation and pollen staining with I2-IK. The results were as follows: 1) The same test line could restore the CMS-C line at a certain genetic background, but failed to restore the CMS-C line at the other genetic backgrounds, suggesting that the genetic background of CMS-C lines plays an important role in the fertility restoration. 2) The fertile-to-sterile segregation ratio of (C48 2*A619) F2 population planted in both Sichuan and Yunnan fited well to 15:1 by the chi 2 test. However, the fertility level of individuals in Yunnan mainly belonged to the 3 and 4grades, but which in Sichuan mainly belonged to the 5 grade, indicating the environmental factors had effect on the fertility restoration reaction of (C48-2*A619) F2. 3) In our study, 18 bai could not restore C478, and 48-2 could not restore C478, but the fertile and sterile segregated plants were unexpectedly found in their double-cross population [(C478*18 bai) F1S*(C48-2*18 bai) F1F]. The similar case was also observed in the double-cross population [(C48-2 * zi 330) F1S * (C478 * zi 330) F1F]. Therefore, we speculated that there are minor fertility restorer genes not only in the nuclear background of C48-2 and C478, but also in zi 330 and 18 bai, and when these minor genes were gathered by hybridization, they could restore the fertility of C478 and C48-2. This conforms to the restorer genes dose-effect for fertility restoration in the plant CMS system. These results not only contribute to our understanding of the complexity and diversity of CMS-C restoration mechanism, but also provide an important reference for the practical applications about maize CMS-C. PMID- 29785949 TI - [The functions of yhcZ gene during Bacillus thuringiensis growth]. AB - yhcZ and yhcY genes constitute a two-component system in Bacillus subtilis and B. cereus that regulates bacterial growth. However, the exact biological function of yhcZ gene in B. thuringiensis has not been fully elucidated. In this study, we proved that HD73_5824 is an yhcZ gene in B. thuringiensis subsp. kurstaki HD73 strain by combining gene functional annotation, analysis of upstream and downstream genes arrangement, and amino acid sequence alignment. This yhcZ gene may co-regulate bacterial growth with HD73_5825 gene (yhcY gene) by constituting a two-component system. Homologous recombination technology was employed to knock out yhcZ gene of HD73, resulting in a mutant strain HD (DeltayhcZ). The HD (DeltayhcZ) strain grew slower than wild-type strain HD73 in both LB and SSM medium. Re-introduction of yhcZ gene in HD (DeltayhcZ) strain can partially restore the growth, indicating that the deletion of yhcZ gene impacts the cell growth of HD73 strain. HD (DeltayhcZ) strain grew faster than HD73 strain in M9 medium with 0.4% glucose as the sole carbon source, implying that the yhcZ gene plays an important role in glucose utilization by HD73 strain. The results of biolog assay showed that HD (DeltayhcZ) exhibits a lower average well color development compared to HD73. HD(DeltayhcZ) cells also demonstrated a decreased capacity for absorbing and utilizing D/L-serine, formic acid, D-gluconic acid, L histamine, D-methyl lactate, and citric acid, indicating that yhcZ gene could dramatically influence carbon source utilization of HD73 strains. Additionally, HD (DeltayhcZ) was less resistant to 8% NaCl, suggesting that yhcZ gene may be involved in the expression and regulation of genes related to high-salt stress response in bacterial cells. The results above show that the yhcZ gene significantly promotes glucose and other carbon sources utilization of HD73 strain during growth. Our findings will lay a foundation not only for analyzing the regulatory mechanisms of glucose and carbon sources utilization by yhcZ gene, but also providing a reference for the further research on bacterial growth and fermentation. PMID- 29785950 TI - Society's expectations of women contribute to pay gap. PMID- 29785951 TI - The Grand Social Experiment at 70: Who is really paying for your NHS? PMID- 29785953 TI - Assisted dying: Guernsey rejects proposal to move towards legalisation. PMID- 29785954 TI - Women are under-represented in the Clinical Excellence Awards. PMID- 29785952 TI - Diagnostic accuracy of point-of-care natriuretic peptide testing for chronic heart failure in ambulatory care: systematic review and meta-analysis. AB - OBJECTIVE: To assess the diagnostic accuracy of point-of-care natriuretic peptide tests in patients with chronic heart failure, with a focus on the ambulatory care setting. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase, Health Technology Assessment Database, Science Citation Index, and Conference Proceedings Citation Index until 31 March 2017. STUDY SELECTION: Eligible studies evaluated point-of care natriuretic peptide testing (B-type natriuretic peptide (BNP) or N terminal fragment pro B-type natriuretic peptide (NTproBNP)) against any relevant reference standard, including echocardiography, clinical examination, or combinations of these, in humans. Studies were excluded if reported data were insufficient to construct 2*2 tables. No language restrictions were applied. RESULTS: 42 publications of 39 individual studies met the inclusion criteria and 40 publications of 37 studies were included in the analysis. Of the 37 studies, 30 evaluated BNP point-of-care testing and seven evaluated NTproBNP testing. 15 studies were done in ambulatory care settings in populations with a low prevalence of chronic heart failure. Five studies were done in primary care. At thresholds >100 pg/mL, the sensitivity of BNP, measured with the point-of-care index device Triage, was generally high and was 0.95 (95% confidence interval 0.90 to 0.98) at 100 pg/mL. At thresholds <100 pg/mL, sensitivity ranged from 0.46 to 0.97 and specificity from 0.31 to 0.98. Primary care studies that used NTproBNP testing reported a sensitivity of 0.99 (0.57 to 1.00) and specificity of 0.60 (0.44 to 0.74) at 135 pg/mL. No statistically significant difference in diagnostic accuracy was found between point-of-care BNP and NTproBNP tests. CONCLUSIONS: Given the lack of studies in primary care, the paucity of NTproBNP data, and potential methodological limitations in these studies, large scale trials in primary care are needed to assess the role of point-of-care natriuretic peptide testing and clarify appropriate thresholds to improve care of patients with suspected or chronic heart failure. PMID- 29785955 TI - Is it time to get out of the car for physical activity benefits? PMID- 29785956 TI - Using alternatives to the car and risk of all-cause, cardiovascular and cancer mortality. AB - OBJECTIVE: To investigate the associations between using alternatives to the car which are more active for commuting and non-commuting purposes, and morbidity and mortality. METHODS: We conducted a prospective study using data from 3 58 799 participants, aged 37-73 years, from UK Biobank. Commute and non-commute travel were assessed at baseline in 2006-2010. We classified participants according to whether they relied exclusively on the car or used alternative modes of transport that were more active at least some of the time. The main outcome measures were incident cardiovascular disease (CVD) and cancer, and CVD, cancer and all-cause mortality. We excluded events in the first 2 years and conducted analyses separately for those who regularly commuted and those who did not. RESULTS: In maximally adjusted models, regular commuters with more active patterns of travel on the commute had a lower risk of incident (HR 0.89, 95% CI 0.79 to 1.00) and fatal (HR 0.70, 95% CI 0.51 to 0.95) CVD. Those regular commuters who also had more active patterns of non-commute travel had an even lower risk of fatal CVD (HR 0.57, 95% CI 0.39 to 0.85). Among those who were not regular commuters, more active patterns of travel were associated with a lower risk of all-cause mortality (HR 0.92, 95% CI 0.86 to 0.99). CONCLUSIONS: More active patterns of travel were associated with a reduced risk of incident and fatal CVD and all cause mortality in adults. This is an important message for clinicians advising people about how to be physically active and reduce their risk of disease. PMID- 29785958 TI - Association Between Hypertensive Disorders in Pregnancy and Particulate Matter in the Contiguous United States, 1999-2004. AB - Hypertensive disorders in pregnancy harm both maternal and infant health and have been linked to ambient particulate matter. However, existing studies are restricted to a local scale and remain inconsistent. A large-scale study is required to enrich the epidemiological evidence and explore the potential sources of the inconsistency. Making use of US birth certificates (1999-2004), and monitoring data from the environmental protection agency air quality networks, we associated hypertensive disorders in pregnancy with maternal exposure to fine particles or coarse particles using logistic regression analysis after adjusting for many covariates among >5 million subjects in the contiguous United States. Additional analyses were conducted to examine variations in the associations according to (1) census divisions; (2) individual-level factors; (3) a socioeconomic indicator, county-level poverty; and (4) the concentration of ambient particles. The results indicated that hypertensive disorders in pregnancy were robustly linked to maternal exposure to fine particles with an adjusted odds ratio of 1.10 (95% confidence intervals, 1.08-1.12) per 5 MUg/m3 increment in terms of the entire pregnancy mean. Stronger associations were found among white mothers. There were also considerable variations in the association by census division or poverty level among counties. Nonlinear analysis indicated a sublinear dose-response function with a threshold concentration of 9 MUg/m3 Based on the national study, we calculated the population attributable fractions and found that 8.1% (6.8%-9.4%) of hypertensive disorder cases were attributable to an entire pregnancy exposure of fine particles. These findings can help policymakers to plan related interventions. PMID- 29785959 TI - Common Carotid Artery Diameter and Risk of Cardiovascular Events and Mortality: Pooled Analyses of Four Cohort Studies. AB - Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure-related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67+/-9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter <7 mm) had a higher incidence of stroke (hazard ratio, 1.5; 95% confidence interval, 1.1-2.0). From all estimates of processes underlying arterial remodeling, adjustment for carotid intima-media thickness attenuated this association (hazard ratio after adjustment for intima-media thickness, 1.2; 95% confidence interval, 0.9-1.6). Larger carotid diameter was associated with risk of CVD and mortality but not clearly with coronary heart disease risk. We showed that a larger carotid diameter is associated with incident stroke, CVD, and mortality. Carotid intima-media thickness, a measure of blood pressure-related media thickening, partially explained the association with stroke incidence. PMID- 29785960 TI - Reduction in Regulatory T Cells in Early Pregnancy Causes Uterine Artery Dysfunction in Mice. AB - Preeclampsia, fetal growth restriction, and miscarriage remain important causes of maternal and perinatal morbidity and mortality. These complications are associated with reduced numbers of a specialized T lymphocyte subset called regulatory T cells (Treg cells) in the maternal circulation, decidua, and placenta. Treg cells suppress inflammation and prevent maternal immunity toward the fetus, which expresses foreign paternal alloantigens. Treg cells are demonstrated to contribute to vascular homeostasis, but whether Treg cells influence the vascular adaptations essential for a healthy pregnancy is unknown. Thus, using a mouse model of Treg-cell depletion, we investigated the hypothesis that depletion of Treg cells would cause increased inflammation and aberrant uterine artery function. Here, we show that Treg-cell depletion resulted in increased embryo resorption and increased production of proinflammatory cytokines. Mean arterial pressure exhibited greater modulation by NO in Treg cell deficient mice because the L-NG-nitroarginine methyl ester-induced increase in mean arterial pressure was 46% greater compared with Treg cell-replete mice. Uterine artery function, which is essential for the supply of nutrients to the placenta and fetus, demonstrated dysregulated hemodynamics after Treg-cell depletion. This was evidenced by increased uterine artery resistance and pulsatility indices and enhanced conversion of bET-1 (big endothelin-1) to the active and potent vasoconstrictor, ET-1 (endothelin-1). These data demonstrate an essential role for Treg cells in modulating uterine artery function during pregnancy and implicate Treg-cell control of maternal vascular function as a key mechanism underlying normal fetal and placental development. PMID- 29785961 TI - Trajectories of Childhood Blood Pressure and Adult Left Ventricular Hypertrophy: The Bogalusa Heart Study. AB - This longitudinal study aims to characterize longitudinal blood pressure (BP) trajectories from childhood and examine the impact of level-independent childhood BP trajectories on adult left ventricular hypertrophy (LVH) and remodeling patterns. The longitudinal cohort consisted of 1154 adults (787 whites and 367 blacks) who had repeated measurements of BP 4 to 15 times from childhood (4-19 years) to adulthood (20-51 years) and assessment of echocardiographic LV dimensions in adulthood. Model-estimated levels and linear slopes of BP at childhood age points were calculated in 1-year intervals using the growth curve parameters and their first derivatives, respectively. Linear and nonlinear curve parameters of BP showed significant race and sex differences from age 15 years onwards. Adults with LVH had higher long-term BP levels than adults with normal LVM in race-sex groups. Linear and nonlinear slope parameters of BP differed consistently and significantly between LVH and normal groups. Associations of level-independent linear slopes of systolic BP with adult LVH were significantly inverse (odds ratio=0.75-0.82; P=0.001-0.015) in preadolescent children of 4 to 9 years but significantly positive (odds ratio=1.29-1.46; P=0.001-0.008) in adolescents of 13 to 19 years, adjusting for covariates. These associations were consistent across race-sex groups. Of note, the association of childhood BP linear slopes with concentric LVH was significantly stronger than that with eccentric LVH during the adolescence period of 12 to 19 years. These observations indicate that the impact of BP trajectories on adult LVH and geometric patterns originates in childhood. Adolescence is a crucial period for the development of LVH in later life, which has implications for early prevention. PMID- 29785962 TI - Age-Related Blood Pressure Sensitivity to Aldosterone in Blacks and Whites. AB - Aldosterone sensitivity, defined as the magnitude of the association of plasma aldosterone concentration with blood pressure (BP), seems to be a function of plasma volume. It increases as plasma renin activity decreases, and it is more significant in blacks but less so in whites. Age is a strong determinant of BP, and an increase in aldosterone sensitivity could contribute to the increase in BP. In the present study, we tested the hypothesis that aldosterone sensitivity increases with age. We used observational data collected from normotensive blacks and whites enrolled in a prospective cohort study. They were studied as children (248 blacks/357 whites) and again as young adults (74 blacks/125 whites) over an age range of 7 to 39 years. A varying-coefficient regression analysis was used to explore the influences of aldosterone on systolic BP. After controlling for body mass index, race, and sex, both plasma renin activity and plasma aldosterone concentration were lower in blacks, and their levels declined with age (P<0.001). In blacks, plasma aldosterone concentration decreased 0.25 ng/dL per year; in whites, plasma aldosterone concentration decreased 0.18 per year. Aldosterone's effect on BP, characterized by a smooth function of age, intensified as age increased, especially in blacks (P<0.01), suggesting an increased aldosterone sensitivity with age. In comparison to blacks, age-related changes in aldosterone sensitivity in whites were not statistically significant. These findings extend the rationale for targeting aldosterone in the treatment of hypertension, especially in blacks. PMID- 29785957 TI - Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults. AB - OBJECTIVE: To examine the associations between egg consumption and cardiovascular disease (CVD), ischaemic heart disease (IHD), major coronary events (MCE), haemorrhagic stroke as well as ischaemic stroke. METHODS: During 2004-2008, over 0.5 million adults aged 30-79 years were recruited from 10 diverse survey sites in China. Participants were asked about the frequency of egg consumption and were followed up via linkages to multiple registries and active investigation. Among 461 213 participants free of prior cancer, CVD and diabetes, a total of 83 977 CVD incident cases and 9985 CVD deaths were documented, as well as 5103 MCE. Stratified Cox regression was performed to yield adjusted hazard ratios for CVD endpoints associated with egg consumption. RESULTS: At baseline, 13.1% of participants reported daily consumption (usual amount 0.76 egg/day) and 9.1% reported never or very rare consumption (usual amount 0.29 egg/day). Compared with non-consumers, daily egg consumption was associated with lower risk of CVD (HR 0.89, 95% CI 0.87 to 0.92). Corresponding multivariate-adjusted HRs (95% CI) for IHD, MCE, haemorrhagic stroke and ischaemic stroke were 0.88 (0.84 to 0.93), 0.86 (0.76 to 0.97), 0.74 (0.67 to 0.82) and 0.90 (0.85 to 0.95), respectively. There were significant dose-response relationships of egg consumption with morbidity of all CVD endpoints (P for linear trend <0.05). Daily consumers also had an 18% lower risk of CVD death and a 28% lower risk of haemorrhagic stroke death compared to non-consumers. CONCLUSION: Among Chinese adults, a moderate level of egg consumption (up to <1 egg/day) was significantly associated with lower risk of CVD, largely independent of other risk factors. PMID- 29785965 TI - Inflammatory bowel disease increases the risk of Parkinson's disease: a Danish nationwide cohort study 1977-2014. AB - OBJECTIVE: Intestinal inflammation has been suggested to play a role in development of Parkinson's disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD and MSA, we performed a nationwide population-based cohort study. DESIGN: The cohort consisted of all individuals diagnosed with IBD in Denmark during 1977-2014 (n=76 477) and non-IBD individuals from the general population, who were comparable in terms of gender, age and vital status (n=7 548 259). All cohort members were followed from IBD diagnosis/index date to occurrence of PD and MSA (according to the Danish National Patient Register). RESULTS: Patients with IBD had a 22% increased risk of PD as compared with non-IBD individuals (HR=1.22; 95% CI 1.09 to 1.35). The increased risk was present independently of age at IBD diagnosis, gender or length of follow-up. The overall incidence of MSA was low in our study, and the regression analysis suggested a tendency towards higher risk of developing MSA in patients with IBD as compared with non-IBD individuals (HR=1.41; 95% CI 0.82 to 2.44). Estimates were similar for women and men. The increased risk of parkinsonism was significantly higher among patients with UC (HR=1.35; 95% CI 1.20 to 1.52) and not significantly different among patients with Crohn's disease (HR=1.12; 95% CI 0.89 to 1.40). CONCLUSIONS: This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent basic scientific findings of a potential role of GI inflammation in development of parkinsonian disorders. PMID- 29785963 TI - SWI/SNF and RSC cooperate to reposition and evict promoter nucleosomes at highly expressed genes in yeast. AB - The nucleosome remodeling complex RSC functions throughout the yeast genome to set the positions of -1 and +1 nucleosomes and thereby determines the widths of nucleosome-depleted regions (NDRs). The related complex SWI/SNF participates in nucleosome remodeling/eviction and promoter activation at certain yeast genes, including those activated by transcription factor Gcn4, but did not appear to function broadly in establishing NDRs. By analyzing the large cohort of Gcn4 induced genes in mutants lacking the catalytic subunits of SWI/SNF or RSC, we uncovered cooperation between these remodelers in evicting nucleosomes from different locations in the promoter and repositioning the +1 nucleosome downstream to produce wider NDRs-highly depleted of nucleosomes-during transcriptional activation. SWI/SNF also functions on a par with RSC at the most highly transcribed constitutively expressed genes, suggesting general cooperation by these remodelers for maximal transcription. SWI/SNF and RSC occupancies are greatest at the most highly expressed genes, consistent with their cooperative functions in nucleosome remodeling and transcriptional activation. Thus, SWI/SNF acts comparably with RSC in forming wide nucleosome-free NDRs to achieve high level transcription but only at the most highly expressed genes exhibiting the greatest SWI/SNF occupancies. PMID- 29785966 TI - Novel prep-less X-ray imaging capsule for colon cancer screening: a feasibility study. PMID- 29785968 TI - Force-activatable coating enables high-resolution cellular force imaging directly on regular cell culture surfaces. AB - Integrin-transmitted cellular forces are crucial mechanical signals regulating a vast range of cell functions. Although various methods have been developed to visualize and quantify cellular forces at the cell-matrix interface, a method with high performance and low technical barrier is still in demand. Here we developed a force-activatable coating (FAC), which can be simply coated on regular cell culture apparatus' surfaces by physical adsorption, and turn these surfaces to force reporting platforms that enable cellular force mapping directly by fluorescence imaging. The FAC molecule consists of an adhesive domain for surface coating and a force-reporting domain which can be activated to fluoresce by integrin molecular tension. The tension threshold required for FAC activation is tunable in 10-60 piconewton (pN), allowing the selective imaging of cellular force contributed by integrin tension at different force levels. We tested the performance of two FACs with tension thresholds of 12 and 54 pN (nominal values), respectively, on both glass and polystyrene surfaces. Cellular forces were successfully mapped by fluorescence imaging on all the surfaces. FAC-coated surfaces also enable co-imaging of cellular forces and cell structures in both live cells and immunostained cells, therefore opening a new avenue for the study of the interplay of force and structure. We demonstrated the co-imaging of integrin tension and talin clustering in live cells, and concluded that talin clustering always occurs before the generation of integrin tension above 54 pN, reinforcing the notion that talin is an important adaptor protein for integrin tension transmission. Overall, FAC provides a highly convenient approach that is accessible to general biological laboratories for the study of cellular forces with high sensitivity and resolution, thus holding the potential to greatly boost the research of cell mechanobiology. PMID- 29785964 TI - Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters. AB - RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. PMID- 29785967 TI - Eighty routes to a ribonucleotide world; dispersion and stringency in the decisive selection. AB - We examine the initial emergence of genetics; that is, of an inherited chemical capability. The crucial actors are ribonucleotides, occasionally meeting in a prebiotic landscape. Previous work identified six influential variables during such random ribonucleotide pooling. Geochemical pools can be in periodic danger (e.g., from tides) or constant danger (e.g., from unfavorable weather). Such pools receive Gaussian nucleotide amounts sporadically, at random times, or get varying substrates simultaneously. Pools use cross-templated RNA synthesis (5'-5' product from 5'-3' template) or para-templated (5'-5' product from 5'-5' template) synthesis. Pools can undergo mild or strong selection, and be recently initiated (early) or late in age. Considering >80 combinations of these variables, selection calculations identify a superior route. Most likely, an early, sporadically fed, cross-templating pool in constant danger, receiving >=1 mM nucleotides while under strong selection for a coenzyme-like product, will host selection of the first encoded biochemical functions. Predominantly templated products emerge from a critical event, the starting bloc selection, which exploits inevitable differences among early pools. Favorable selection has a simple rationale; it is increased by product dispersion (SD/mean), by selection intensity (mild or strong), or by combining these factors as stringency, reciprocal fraction of pools selected (1/sfsel). To summarize: chance utility, acting via a preference for disperse, templated coenzyme-like dinucleotides, uses stringent starting bloc selection to quickly establish majority encoded/genetic expression. Despite its computational origin, starting bloc selection is largely independent of specialized assumptions. This ribodinucleotide route to inheritance may also have facilitated 5'-3' chemical RNA replication. PMID- 29785969 TI - Pillared graphite anodes for reversible sodiation. AB - There has been a major effort recently to develop new rechargeable sodium-ion electrodes. In lithium ion batteries, LiC6 forms from graphite and desolvated Li cations during the first charge. With sodium ions, graphite only shows a significant capacity when Na+ intercalates as a solvated complex, resulting in ternary graphite intercalation compounds (GICs). Although this chemistry has been shown to be highly reversible and to support high rates in small test cells, these GICs can require >250% volume expansion and contraction during cycling. Here we demonstrate the first example of GICs that reversibly sodiate/desodiate without any significant volume change. These pillared GICs are obtained by electrochemical reduction of graphite in an ether/amine co-solvent electrolyte. The initial gallery expansion, 0.36 nm, is less than half of that in diglyme based systems, and shows a similar capacity. Thermal analyses suggest the pillaring phenomenon arises from stronger co-intercalate interactions in the GIC galleries. PMID- 29785971 TI - Community noise exposure and annoyance, activity interference, and academic achievement among university students. AB - Background: Noise annoyance and effects on academic performance have been investigated for primary and secondary school students but comparatively little work has been conducted with university students who generally spend more time in dormitories or accommodation for their self-study. Objective: To determine, using a socio-acoustic approach involving face-to-face interviews and actual noise measurements, the effect of various community noise sources on student activities in accommodation both inside and outside a university precinct and also relationships with cumulative grade point average (GPA). Materials and Methods: The study sample comprised a student group resident off-campus (n = 450) and a control group resident in dormitories on-campus (n = 336). Noise levels [LA (dB)] were measured at both locations according to International Organization for Standardization standards. The extent of community noise interference with the student activities was examined with bivariate and stratified analyses and results presented as Mantel-Haenszel weighted odds ratios (ORMH) with 95% confidence intervals. Binary logistic regression was employed to assess the association between noise-disturbed student activities and dichotomized GPA values and derive odds ratios (ORs) for these associations. Results: Measured noise levels were all significantly (P < 0.05) higher for off-campus students. This was not reflected in the interviewed students' subjective perceptions of how "noisy" their respective environments were. The off-campus student cohort was, however, more annoyed by all community noise categories (P < 0.001) except road traffic noise. For impact on specific student activities, the largest differences between on- and off-campus students were found for telephone and personal communication regardless of the type of community noise. There was no significant difference in the relationships between perceived annoyance due to community noise categories and cumulative GPA in the off-campus group compared to those for on-campus residents with ORMH values ranging from 1.049 to 1.164. The most important noise-impacted factors affecting off-campus students' cumulative GPA were reading and mental tasks (OR = 2.801). Rest disturbance had a positive influence on cumulative GPA for on-campus students. Conclusion: These results provide support that various contemporary community noise sources affect university students' activities and possibly influence their educational achievement as well. PMID- 29785970 TI - Phenotypic and molecular characteristics of androgen insensitivity syndrome patients. AB - Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel (c.2112 C>G[p.S704R], c.2290T>A[p.Y764N], c.2626C>T[p.Q876X], c.933dupC[p.K313Qfs*28], and c.1067delC[p.A356Efs*123]); the other five were previously reported (c.1789G>A[p.A597T], c.2566C>T[p.R856C], c.2668G>A[p.V890M], c.2679C>T[p.P893L], and c.1605C>G[p.Y535X]). Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% (3/10) of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening. PMID- 29785972 TI - A methodology to objectively assess the performance of sound field amplification systems demonstrated using 50 physical simulations of classroom conditions. AB - Introduction: The effect of a sound reinforcement system, in terms of speech intelligibility, has been systematically determined under realistic conditions. Different combinations of ambient and reverberant conditions representative of a classroom environment have been investigated. Materials and Methods: By comparing the measured speech transmission index metric with and without the system in the same space under different room acoustics conditions, it was possible to determine when the system was most effective. A new simple criterion, equivalent noise reduction (ENR), was introduced to determine the effectiveness of the sound reinforcement system which can be used to predict the speech transmission index based on the ambient sound pressure and reverberation time with and without amplification. Results: This criterion had a correlation, R2 > 0.97. It was found that sound reinforcement provided no benefit if the competing noise level was less than 40 dBA. However, the maximum benefit of such a system was equivalent to a 7.7 dBA noise reduction. Conclusion: Using the ENR model, it would be possible to determine the suitability of implementing sound reinforcement systems in any room, thus providing a tool to determine if natural acoustic treatment or sound field amplification would be of most benefit to the occupants of any particular room. PMID- 29785973 TI - Effect of systematic desensitization training on acceptable noise levels in adults with normal hearing sensitivity. AB - Context: The willingness of a person to accept noise while listening to speech can be measured using the acceptable noise level (ANL) test. Individuals with poor ANL are unlikely to become successful hearing aid users. Hence, it is important to enhance the individual's ability to accept noise levels. The current study was an attempt to investigate whether systematic desensitization training can improve the ANL in individuals having high ANL. Aims: To investigate the effect of systematic desensitization training on ANLs in individuals with normal hearing sensitivity. Settings and Design: Observational study design. Materials and Methods: Thirty-eight normally hearing adults within the age range of 18-25 years participated in the study. Initially, baseline ANL was measured for all participants. Based on the baseline ANL, participants were categorized into three groups; low ANL, mid ANL, and high ANL. The participants with high ANL were trained using systematic desensitization procedure whereas, individuals with low and mid ANL did not undergo any training and served as the comparison groups. After the training period, ANL was measured again for all the participants. Statistical Analysis Used: Repeated measures of analysis of variance with follow up paired "t" test. Results: Analysis revealed a significant main effect of systematic desensitization training on ANL. There was a significant improvement in ANL in participants with high ANL. However, there was no significant difference in ANL between baseline and follow-up session in individuals with low and mid ANL. Conclusions: Systematic desensitization training can facilitate ANL, thereby enhancing the individual's ability to accept the noise levels. This enhanced ANL can facilitate better hearing aid fitting and acceptance. PMID- 29785974 TI - Railway noise annoyance on the railway track in northwest slovakia. AB - Introduction: This paper describes an assessment of noise caused by railway traffic in a large high-loaded railway track in Northwest Slovakia. Materials and Methods: The measurements of noise levels generated by trains passing through residential neighborhoods were taken. Noise maps were also calculated showing noise pollution generated by the train traffic. In addition, the annoyance level and sleep disturbance of residents affected by railway noise were evaluated by a validated questionnaire on a pilot sample of 107 respondents living near the important railway track. Results: The measurements indicated that the noise levels generated by the passage of the train were extremely high especially at night, clearly exceeding the nighttime limits of equivalent sound pressure level established by the Decree of the Slovak Ministry of Health (No.549/2007) (LAeq = 55 dB). Measurements at one point during the night exceeded the limit values of up to 17.4 dB. The residents reported feeling affected by the noise generated by passing trains, which caused irritability, headache, poor concentration, and insomnia. In addition, 19.64% of the residents claimed that nocturnal noise pollution was the most distressing. The results of bivariate analysis showed a higher risk of annoyance especially for railway noise [ORMH = 7.80 (4.02-15.14)] and the noise from industry [ORMH = 3.08 (1.72-5.50)] in the exposed location. Discussion: The effects of railway traffic on annoyance/sleep and psychosocial well-being were evaluated in a few studies. In accordance with our results the railway noise mostly disturbs sleep and rest of the respondents. Conclusion: The pilot survey showed the importance of sleep and rest disturbance by railway noise and the possibilities of getting worse health condition in the future. Noise abatement measures and strategies should, therefore, be implemented in an effective and manageable way increasing the environmental advantages of rail transport. PMID- 29785975 TI - Utility of otoacoustic emissions and olivocochlear reflex in predicting vulnerability to noise-induced inner ear damage. AB - Aim: The aim of the present study was to explore the possible utility of otoacoustic emissions (OAEs) and efferent system strength to determine vulnerability to noise exposure in a clinical setting. Materials and Methods: The study group comprised 344 volunteers who had just begun mandatory basic training as Hellenic Corps Officers Military Academy cadets. Pure-tone audiograms were obtained on both ears. Participants were also subjected to diagnostic transient evoked otoacoustic emissions (TEOAEs). Finally, they were all tested for efferent function through the suppression of TEOAEs with contralateral noise. Following baseline evaluation, all cadets fired 10 rounds using a 7.62 mm Heckler & Koch G3A3 assault rifle while lying down in prone position. Immediately after exposure to gunfire noise and no later than 10 h, all participants completed an identical protocol for a second time, which was then repeated a third time, 30 days later. Results: The data showed that after the firing drill, 280 participants suffered a temporary threshold shift (TTS) (468 ears), while in the third evaluation conducted 30 days after exposure, 142 of these ears still presented a threshold shift compared to the baseline evaluation [permanent threshold shift (PTS) ears]. A receiver operating characteristics curve analysis showed that OAEs amplitude is predictive of future TTS and PTS. The results were slightly different for the suppression of OAEs showing only a slight trend toward significance. The curves were used to determine cut points to evaluate the likelihood of TTS/PTS for OAEs amplitude in the baseline evaluation. Decision limits yielding 71.6% sensitivity were 12.45 dB SPL with 63.8% specificity for PTS, and 50% sensitivity were 12.35 dB SPL with 68.2% specificity for TTS. Conclusions: Interestingly, the above data yielded tentative evidence to suggest that OAEs amplitude is both sensitive and specific enough to efficiently identify participants who are particularly susceptible to hearing loss caused by impulse noise generated by firearms. Hearing conservation programs may therefore want to consider including such tests in their routine. As far as efferent strength is concerned, we feel that further research is due, before implementing the suppression of OAEs in hearing conservations programs in a similar manner. PMID- 29785976 TI - The study of attenuation levels and the comfort of earplugs. AB - Introduction: This study aimed to analyze and compare four different types of earplugs, divided into premolded plugs and foam plug models, in relation to the level of attenuation, comfort, and the size of the external acoustic meatus (EAM) in an attempt to identify how these variables influence the choice of specific hearing protection devices (HPDs). Materials and Methods: A cross-sectional observational study was performed in a sample of 49 participants, oriented toward the ideal placement of four HPDs, two premolded and two foam plugs (3MTM). The procedures included otoscopy, EAM diameter measurement using an otometer, EAM volume measurement via an acoustic impedance test, and the obtainment of the bilateral personal attenuation rating (PAR) for each HPD using the E-A-RfitTM Validation System (3MTM). The Bipolar Comfort Rating Scale (BCRS) instrument was applied twice for each individual: once after the evaluations with the premolded HPDs and again after the evaluations with the foam plug HPDs. Then, each participant was asked which was his/her favorite protector. Results: The volume of the EAM was not directly related to the diameter of the EAM. The attenuation did not interfere with the HPD preference, and the PAR of the foam plug was significantly higher regardless of the preferred HPD. Regarding the BCRS, the variables "Placement," "Complexity," and "Occlusion Effect" had higher scores for premolded HPDs and had a direct relationship with the type of preferred HPD. Conclusion: Attention to the use of HPDs should be personalized, taking into account the needs of each individual, considering not only the attenuation, but also the user's reported well-being. PMID- 29785977 TI - Steps to standardize ophthalmology residency programs in India. PMID- 29785979 TI - Residency training in India: Time for a course correction. PMID- 29785978 TI - Elevating ophthalmic education and practice in India. PMID- 29785980 TI - Transformation of nevus to melanoma, or not? PMID- 29785981 TI - Education in ophthalmology over the past 60 years. AB - This paper summarizes the personal experience of an ophthalmologist who has been involved in medical education for over 60 years. With clinical experience and leadership positions within ophthalmology and in broad medical organizations, this paper chronicles the evolution of educational practice and approaches for over a half-century. PMID- 29785982 TI - A national curriculum for ophthalmology residency training. AB - We present a residency curriculum for Ophthalmology in India. The document derives from a workshop by the All India Ophthalmological Society (AlOS) which adapted the International Council of Ophthalmology residency curriculum and refined and customized it based on inputs by the residency program directors who participated in the work shop. The curriculum describes the course content, lays down the minimum requirements of infrastructure and mandates diagnostic and therapeutic procedures required for optimal training. It emphasises professionalism, management, research methodology, community ophthalmology as integral to the curriculum. The proposed national ophthalmology residency curriculum for India incorporates the required knowledge and skills for effective and safe practice of ophthalmology and takes into account the specific needs of the country. PMID- 29785983 TI - Take time to sharpen the saw. PMID- 29785984 TI - Residency Evaluation and Adherence Design Study III: Ophthalmology residency training in India: Then and now-Improving with time? AB - Purpose: To gauge the differences in ophthalmology residency training, academic, clinical and surgical, in the last three decades of the 20th century and the first decade of the 21st century. Methods: A survey was conducted by the Academic and Research Committee of the All India Ophthalmological Society, in 2014-2016, using a prevalidated questionnaire, which was circulated to ophthalmologists to gauge the practicality of the teaching protocols of clinical and surgical skills during postgraduate residency program. Results: Of the 1005 respondents, 320 ophthalmologists who completed residency between 1967 and 2002 (20th century trained) and 531 who completed a residency in 2003-2012 (21st century trained) fulfilled the inclusion criteria. The average age was 49.2 years (standard deviation [SD] 4) and 32.6 years (SD 4), respectively. Twenty-first century trained ophthalmologists rated their training significantly better than the 20th century trained ophthalmologists for slit lamp examination (P = 0.001), indirect ophthalmoscopy, gonioscopy, automated perimetry, optical coherence tomography, and fundus photography (all having P < 0.001), while the 20th century trained rated their teaching of refraction, synoptophore, diplopia charting better (all P < 0.001). The range of grading was 0-10 in all categories. The median number of surgeries performed independently by 20th century and 21st century trained (during their training period) were: intracapsular cataract extraction (ICCE) 10, 0; extracapsular cataract extraction (ECCE) 43, 18; small incision cataract surgery (SICS) 5, 55; phacoemulsification (Phaco) 0, 1; pterygium excision 20, 15; dacryocystectomy 11, 4; dacryocystorhinostomy 11, 2; chalazion 35, 30; trabeculectomies 5, 0; strabismus correction 0, 0; vitrectomy 0, 0; keratoplasty 0, 0; eyelid surgery 6, 2; and ocular emergencies 18, 20. Conclusion: Teaching of many clinical skills had improved over decades. Cataract surgery training has shifted from ICCE and ECCE to SICS and Phaco, but other surgeries were still taught sparingly. There was an enormous variation across the country in residency training which needs immediate attention. PMID- 29785986 TI - Effect of wet-laboratory training on resident-performed manual small-incision cataract surgery. PMID- 29785985 TI - Effect of wet-laboratory training on resident performed manual small-incision cataract surgery. AB - Purpose: The aim of this study was to study the effect of wet-laboratory training on the surgical outcome of resident performed manual small-incision cataract surgery (MSICS). Methods: We conducted a retrospective, comparative observational study on resident performed MSICS in our institute. We collected data of 464 patients of which Group A had 232 cases performed by residents without prior wet laboratory training and Group B had 232 resident performed cases after adequate skill training in the wet laboratory. The demographics, type of cataract, intraoperative, postoperative complications, and immediate visual outcome were compared between the two groups. Results: The age, sex, and type of cataract were similar in both groups of residents. The frequency of intraoperative complications was higher in Group A (23.7%) than in Group B (15.08%) (P = 0.019). The occurrence of posterior capsule (PC) rupture and vitreous loss showed a statistically significant difference, with Group A showing a high rate of 14.3% PC rent and vitreous loss while only 6.9% (P = 0.01) had this complication in Group B. The postoperative visual outcome also was better in Group B than in Group A, with 62.06% of patients in Group B, having a postoperative day 1 vision of better than 6/18 as compared to only 38.36% in Group A. Conclusion: The wet laboratory training is an effective method of improving the skills of the ophthalmology residents in MSICS. The reduction of complications will improve the quality of surgery and improve the postoperative visual outcome. PMID- 29785987 TI - Variant myopia: A new presentation? AB - Purpose: Variant myopia (VM) presents as a discrepancy of >1 diopter (D) between subjective and objective refraction, without the presence of any accommodative dysfunction. The purpose of this study is to create a clinical profile of VM. Methods: Fourteen eyes of 12 VM patients who had a discrepancy of >1D between retinoscopy and subjective acceptance under both cycloplegic and noncycloplegic conditions were included in the study. Fourteen eyes of 14 age- and refractive error-matched participants served as controls. Potential participants underwent a comprehensive orthoptic examination followed by retinoscopy (Ret), closed-field autorefractor (CA), subjective acceptance (SA), choroidal and retinal thickness, ocular biometry, and higher order spherical aberrations measurements. Results: In the VM eyes, a statistically and clinically significant difference was noted between the Ret and CA and Ret and SA under both cycloplegic and noncycloplegic conditions (multivariate repeated measures analysis of variance, P < 0.0001). A statistically significant difference was observed between the VM eyes, non-VM eyes, and controls for choroidal thickness in all the quadrants (Univariate ANOVA P < 0.05). The VM eyes had thinner choroids (197.21 +/- 13.04 MU) compared to the non-VM eyes (249.25 +/- 53.70 MU) and refractive error-matched controls (264.62 +/- 12.53 MU). No statistically significant differences between groups in root mean square of total higher order aberrations and spherical aberration were observed. Conclusion: Accommodative etiology does not play a role in the refractive discrepancy seen in individuals with the variant myopic presentation. These individuals have thinner choroids in the eye with variant myopic presentation compared to the fellow eyes and controls. Hypotheses and clinical implications of variant myopia are discussed. PMID- 29785988 TI - Accuracy of noncycloplegic refraction performed at school screening camps. AB - Purpose: The aim of this study was to compare noncycloplegic refraction performed in school camp with that performed in eye clinic in children aged 6-16 years. Methods: A prospective study of children with unaided vision <0.2 LogMAR who underwent noncycloplegic retinoscopy (NCR) and subjective refraction (SR) in camp and subsequently in eye clinic between February and March 2017 was performed. A masked optometrist performed refractions in both settings. The agreement between refraction values obtained at both settings was compared using the Bland-Altman analysis. Results: A total of 217 eyes were included in this study. Between the school camp and eye clinic, the mean absolute error +/- standard deviation in spherical equivalent (SE) of NCR was 0.33 +/- 0.4D and that of SR was 0.26 +/- 0.5D. The limits of agreement for NCR were +0.91D to - 1.09D and for SR was +1.15D to -1.06D. The mean absolute error in SE was <=0.5D in 92.62% eyes (95% confidence interval 88%-95%). Conclusion: A certain degree of variability exists between noncycloplegic refraction done in school camps and eye clinic. It was found to be accurate within 0.5D of SE in 92.62% eyes for refractive errors up to 4.5D of myopia, 3D of cylinder, and 1.5D of hyperopia. PMID- 29785989 TI - Cerebral visual impairment in children: Causes and associated ophthalmological problems. AB - Purpose: The aim of this study is to identify common causes, associated ophthalmological abnormalities, and systemic comorbidities in children in Andhra Pradesh, India, with cerebral visual impairment (CVI). Methods: A retrospective review of case records of all children aged <16 years with diagnosis of CVI seen between January 2016 and December 2016 was carried out. Data were collected for their age, gender, cause of CVI, refraction, accommodation, anterior and posterior segment examination findings, and systemic problems. Results: A total of 124 patients were identified and studied (80 boys and 44 girls, mean age 5.23 years, 44.8% aged <2 years). The most common causes of CVI were hypoxic-ischemic encephalopathy (HIE) (34.4%), undetermined etiology (32.8%), neonatal seizures, and infantile spasms (16% each). The most common presenting complaints were poor vision (76%) and squint (11.2%). Profound visual impairment was seen in 88.8%, and 11.2% had high functioning CVI. Fifty-eight (46.4%) patients had significant refractive errors, 40 (32.25%) had strabismus, 4 (3.2%) had visually significant cataract, and 40 (32%) had optic atrophy. Motor delay was observed in 39.5%, speech delay was evident in 22.4%, and cognitive delay in 16%. Conclusion: HIE is the most common cause (one-third) of CVI in our population, and the majority of them presented at age <2 years (44.8%) with profound visual impairment (88.8%). A significant number of them have treatable ophthalmic conditions such as refractive errors (46.4%), accommodative insufficiency (12.1%), and cataract (3.2%), and more than one-third of them also have delay in other areas of development. PMID- 29785990 TI - Continuous intraoperative optical coherence tomography-guided shield ulcer debridement with tuck in multilayered amniotic membrane transplantation. AB - Purpose: The aim of this study is to describe a modified surgical technique of continuous intraoperative optical coherence tomography (iOCT)-guided shield ulcer debridement with tuck-in multilayered Amniotic membrane transplantation (ML AMT) in vernal keratoconjunctivitis (VKC) with shield ulcer with plaque. Methods: Seven eyes of seven patients presenting with VKC with shield ulcer with plaque were enrolled in this prospective case series and planned for shield ulcer debridement with ML AMT. Debridement of the ulcer base with double-layered AMT was done under the continuous guidance of iOCT. The main outcome measure was the time for complete reepithelialization. Statistical analysis was performed using the Stata-14.0 program for Windows. Data were presented as mean +/- standard deviation/median (minimum-maximum) and frequency percentage as applicable. Results: The surgery could be completed successfully in all cases and iOCT could provide real-time assessment of the depth of dissection during the entire procedure. The duration of complete healing and disintegration of amniotic membrane varied from 7 to 12 days. Recurrence was not seen in any case till 2 months follow-up. Conclusion: iOCT provides continuous monitoring of the depth of dissection and allows for a safe and complete debridement of the shield ulcer with plaque. PMID- 29785991 TI - All India Ophthalmological Society members survey results: Cataract surgery antibiotic prophylaxis current practice pattern 2017. AB - Purpose: The purpose of this article is to document the current practice pattern of Indian ophthalmologists for antibiotic prophylaxis in cataract surgery to prevent endophthalmitis. Methods: Fifteen structured questions were sent online to all ophthalmologists registered with the All India Ophthalmological Society. The questionnaire was divided into three main categories of prophylaxis - preoperative, intraoperative, and postoperative. A web-based anonymous survey was conducted, and a unique response link allowed completing the survey only once. We compared the results with a similar 2014 survey among the members of the American Society of Cataract and Refractive Surgeons (ASCRS). Results: The response was received from 30.2% (n = 4292/14,170) ophthalmologists. The results were as follows: all respondents do not prepare the eye with 5% povidone-iodine (83% of them use povidone iodine), majority (90%) use topical antibiotic both pre- and post-operatively, 46% use subconjunctival antibiotic at the end of surgery, and 40% use intracameral antibiotic (46% of them in high-risk patients only). Moxifloxacin was the preferred antibiotic for topical and intracameral use. Comparison with the 2014 ASCRS survey results showed a similarity in decision for pre- and post-operative antibiotics and intracameral antibiotic but dissimilarity in the choice of intracameral antibiotic and decision for subconjunctival antibiotic. Conclusion: The antibiotic prophylaxis practice by the Indian ophthalmologists is not too dissimilar from the practice in North American Ophthalmologists (ASCRS) though all ophthalmologists in India must be nudged to preoperative preparation of the eye with povidone-iodine and discontinue the practice of postoperative subconjunctival and systemic antibiotic. PMID- 29785992 TI - Antibiotic prophylaxis in cataract surgery: Understanding the trends of the day. PMID- 29785993 TI - Factors predicting response of pseudophakic cystoid macular edema to topical steroids and nepafenac. AB - Purpose: The purpose of this study is to determine factors predicting resolution of acute pseudophakic cystoid macular edema (PCME) after 6 weeks of topical prednisolone and nepafenac application. Methods: Case records of patients with a clinical and optical coherence tomography (OCT)-based diagnosis of acute PCME were retrospectively reviewed for best-corrected visual acuity and OCT-based parameters at the time of presentation with PCME. In addition, demographic variables, intraoperative and early postoperative factors, and type of treatment prescribed (tapering vs. nontapering prednisolone, generic vs. branded prednisolone and nepafenac) were recorded from case records for analysis. Complete and any successes were defined and baseline factors predicting complete success at 6 weeks were analyzed. Results: We analyzed 69 eyes of 69 patients out of which complete success with topical medications was seen in 37 eyes (54%) and any success was seen in 55 eyes (80%) at 6 weeks. Multivariable logistic regression showed that eyes with lower vision at presentation had a significantly lower likelihood of experiencing both, complete (odds ratio [OR] = 0.83 with one line decrement in baseline vision, 95% confidence interval [CI] = 0.61-0.89, P = 0.003) and any success (OR = 0.61, 95% CI = 0.4-0.9, P = 0.007). Baseline OCT thickness did not influence success rates. Conclusion: Topical prednisolone and nepafenac lead to resolution in PCME in half of the eyes at 6 weeks. Baseline vision is the only factor predicting rates of success and PCME resolution with topical medications. PMID- 29785994 TI - The efficacy of intravitreal dexamethasone implant as the first-line treatment for retinal vein occlusion-related macular edema in a real-life scenario. AB - Purpose: This study evaluated the effect of intravitreal dexamethasone implant (IDI; Ozurdex) injection for treating macular edema in patients with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Methods: This prospective study included 40 eyes of 40 patients with nonischemic BRVO and 31 eyes of 31 patients with nonischemic CRVO who received IDI injection as the first-line treatment for macular edema. The best-corrected visual acuity (BCVA) value before and after the treatment; intraocular pressure; optic coherence tomography findings; and all ocular examination findings, including central foveal thickness (CFT) measurement and fluorescein angiography findings, were evaluated for each patient. Results: After the IDI injection, BCVA value increased (P < 0.001) and CFT value decreased (P < 0.001) in both groups. The recurrence rates of CFT elevation after the first and the second Ozurdex injections were 65.0% and 65.3%, respectively, in patients with BRVO and 70.9% and 68.1%, respectively, in patients with CRVO. A statistically significant correlation was observed between preinjection CFT value and postinjection recurrence of CFT elevation (P = 0.017). Conclusion: Treatment with the IDI injections resulted in significant short-term improvement in CFT and BCVA values in patients with clinically significant RVO-related macular edema. Moreover, we observed that high preinjection CFT value was associated with a risk of postinjection recurrence of CFT elevation. PMID- 29785996 TI - Phacoemulsification with single-pass four-throw pupilloplasty and pre-Descemet's endothelial keratoplasty for management of cosmetic iris implant complication. AB - Placement of an anterior chamber iris implant for cosmetic reasons has been associated with development of various complications. Even after the implant has been explanted from the eye, it leaves a trail of after effects that necessitate surgical management. We describe a technique that comprises of performing phacoemulsification with single-pass four-throw pupilloplasty and a pre Descemet's endothelial keratoplasty procedure for this eye with cosmetic iris implant complication. PMID- 29785995 TI - Impact on the pattern of ocular injuries and awareness following a ban on firecrackers in New Delhi: A tertiary eye hospital-based study. AB - Purpose: To review the nature of firecracker-related ocular injuries at a tertiary eye hospital in northern India following the firecracker ban and also to review the level of awareness among the victims. Methods: A cross-sectional observational study involving the patients presenting with firecracker-related ocular injuries from October 18 to 27, 2017 were assessed for demographic distribution, detailed ocular evaluation, and a questionnaire related to the awareness about the injuries. Results: A total of 68 patients were observed. Fifty patients (74.5%) were males. This year, a majority of patients were from outside Delhi. Uttar Pradesh constituted the most 38.23% of the patients followed by Haryana 30.88%, Delhi 23.5%, and Bihar 7.35%. Visual acuity varied from 6/6 to no perception of light. Open globe injury was observed in 56 patients (82.35%) who commonly had zone I injury. A significant number of patients (88.23%) were aware of firecracker-related injuries, and a large number of such injuries (58.8%) occurred in those who were not actively involved in the ignition of firecrackers but were in the vicinity. Conclusion: This year, following a ban, the number of firecracker-related ocular injuries reported from areas outside Delhi outnumbered as compared to within Delhi. However, firecracker-related ocular injuries are still a major cause of significant visual loss, especially involving the bystanders. Thus, firecracker-related celebrations should be monitored with a stringent protocol. PMID- 29785997 TI - Endoillumination (chandelier) and wide-angle viewing-assisted fine-needle aspiration biopsy of intraocular mass lesions. AB - Fine-needle aspiration biopsy (FNAB) of intraocular mass lesions is an important intervention in the presence of diagnostic difficulty. FNAB of intraocular mass lesions is also likely to become more commonly recommended for prognostication of tumors such as choroidal melanoma. The most commonly described approach for tumor localization and visualization during FNAB is transillumination and indirect ophthalmoscopic viewing. Herein, we report endoillumination (chandelier) and wide angle viewing assisted, microscope-based approach for FNAB in two patients using two port minimally invasive vitreoretinal surgical approach. The submission is supported by a video demonstration. The entire procedure was completed under the microscope. Adequate sample was obtained. In the first patient, the inflammatory nature of the lesion was confirmed though magnetic resonance imaging had been reported as melanoma. In the second patient, a clinical diagnosis of amelanotic melanoma was confirmed. Endoillumination-assisted FNAB of intraocular mass lesions is easier to learn and more precise and hence carries lesser risks. PMID- 29785998 TI - Acute full-thickness macular hole after uneventful femtosecond-assisted cataract surgery and its spontaneous closure. PMID- 29786000 TI - The fine art of pseudoexfoliation. PMID- 29785999 TI - Swept source optical coherence tomography-angiography of an infarct of a small intra-neural branch of central retinal artery simulating cilio-retinal artery. PMID- 29786001 TI - Sutural cataract. PMID- 29786002 TI - Eyelid Kaposi Sarcoma in an HIV-negative Patient. AB - Kaposi sarcoma (KS) is a low-grade, multicentric vascular neoplasm. Most commonly, it involves the skin, but it can occur at any site on the body. The cutaneous lesions are often located on the lower legs, genitalia, oral mucosa, and face. KS is categorized in four different types: classic, endemic, epidemic or AIDS associated, and transplantation associated. We report a case of HIV negative, classic KS located on the eyelid. The eyelid lesion was completely excised, and after a 1-year follow-up, no recurrences were observed. Ocular involvement by KS in a patient who is serologically negative for HIV is extremely rare. PMID- 29786003 TI - Spontaneous subconjunctival abscess in congenital lamellar ichthyosis. AB - Congenital lamellar ichthyosis is an autosomal recessive, heterogeneous disorder presenting at birth with generalized skin involvement. The most common ophthalmic manifestation noted is bilateral ectropion of the lower eyelids. A 1-month-old female neonate, the second born of a nonconsanguineous marriage, presented with 4 days' history of redness, discharge, and swelling in the right eye. There was severe right upper eyelid ectropion, conjunctival injection, chemosis, a subconjunctival mass on the temporal bulbar conjunctiva spontaneously draining pus and corneal haze. The anterior chamber, iris, lens and fundus appeared normal. Congenital lamellar ichthyosis was suspected because of scaling and excessive dryness of the entire body. The occurrence of a spontaneous subconjunctival abscess is not known in lamellar ichthyosis. We thus report the management of a rare case of unilateral upper eyelid ectropion, subconjunctival abscess with orbital cellulitis in congenital lamellar ichthyosis. PMID- 29786004 TI - Anterior segment optical coherence tomography of intraocular lens opacification. AB - Postoperative opacification of a hydrophilic acrylic intraocular lens (IOL) is an uncommon complication. A 57-year-old diabetic female who had undergone phacoemulsification with IOL implantation in her right eye 16 years back presented with diminution of vision in the same eye for 3 years. Significant IOL opacification was observed clinically and anterior segment optical coherence tomography clearly delineated the intraoptic deposits, sparing the haptics, and edges of the optic. IOL explant and exchange was performed leading to restoration of visual acuity to 6/9. Histochemical evaluation of the IOL confirmed that the hydrophilic acrylic IOL optic had calcium deposits. PMID- 29786005 TI - A microinvasive technique for management of corneal edema secondary to glaucoma drainage device tube-corneal touch. AB - We present a case of tube endothelial touch where a suture technique for repositioning of the Ahmed glaucoma valve was performed. Advantage of this technique is that it is minimally invasive and anterior chamber stability is maintained during the procedure. PMID- 29786006 TI - Rebound inflammation after an intravitreal injection in Vogt-Koyanagi-Harada syndrome. AB - A 43-year-old male with chronic Vogt-Koyanagi-Harada syndrome (VKH) presented with subfoveal choroidal neovascular membrane (CNVM) in the right eye with no evidence of active inflammation. He underwent intravitreal bevacizumab and dexamethasone injections. Postinjection he developed fresh keratic precipitates and exudative retinal detachment (RD). He received two more bevacizumab injections with oral corticosteroids and immunosuppressants causing resolution of exudative RD with scarred CNVM. We report this case to highlight that intravitreal injection may act as a trigger for rebound inflammation in VKH patients and may require anti-inflammatory drugs to be started even in the absence of an active inflammation. PMID- 29786007 TI - Bilateral acute retinal necrosis associated with bilateral uveal effusion in an immunocompetent patient: A challenging association. AB - Bilateral uveal effusion syndrome associated with bilateral acute retinal necrosis is a diagnostic and therapeutic challenge. A 52 year old man presented with bilateral angle closure with choroidal detachment. With restricted fundus view, parenteral steroid was started. During close follow up bilateral discrete areas of peripheral retinitis were noted. Parenteral steroids were promptly stopped and parenteral antivirals with oral steroids were continued. It showed healing response with nil recurrences till last follow up. Aggressive treatment of bilateral uveal effusion with parenteral steroids can cause progression of bilateral acute retinal necrosis leading to phthisis bulbi. However early diagnosis, prompt intervention and close follow up are the key elements to therapeutic success even during diagnostic surprises and avoid costly mistakes. PMID- 29786008 TI - An unexpected complication in bilateral acute iris transillumination: Cystoid macular edema. AB - A 47-year-old male presented with bilateral 4 + circulating pigment in the anterior chamber, diffuse iris transillumination, dilated pupils unresponsive to light, and high intraocular pressure (IOP) levels in both eyes. Visual acuity and IOP improved bilaterally with topical steroid and antiglaucomatous therapy. In the 10th month, bilateral cystoid macular edema (CME) was developed and resolved after subtenon triamcinolone injections. CME recurred after cataract surgery in the right eye which was treated with intravitreal dexamethasone implant injection. CME was recurred in the left eye and treated with intravitreal dexamethasone implant at the same setting with cataract surgery. CME can be seen in the course of bilateral acute iris transillumination (BAIT). This is the first BAIT case presenting with bilateral CME. PMID- 29786010 TI - Commentary: Comparison of optical coherence tomography angiography and fundus fluorescein angiography features of retinal capillary hemangioblastoma. PMID- 29786009 TI - Comparison of optical coherence tomography angiography and fundus fluorescein angiography features of retinal capillary hemangioblastoma. AB - The aim of this study is to compare the optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA) features of retinal capillary hemangioblastoma (RCH). This is an observational case series of three patients with von Hippel-Lindau (VHL) disease and one patient with juxtapapillary RCH. All patients underwent FFA with a mydriatic fundus camera and OCTA with swept-source angio OCT. The FFA and OCTA characteristics of tumors were compared. In our series, FFA could identify tumors as small as the width of a third-order retinal artery, which was missed on clinical examination. OCTA identified these tiny tumors, but only those closer to the posterior pole. Both FFA and OCTA could identify the intrinsic vasculature and feeder vessel in juxtapapillary RCH. On OCTA, the tumors were better defined than in FFA. The depth of the lesion can be identified on OCTA. Feeder and the draining vessels could be identified precisely in OCTA than FFA, particularly in small tumors. OCTA can identify tumors in VHL missed on clinical examination. It can identify the feeder vessel and intrinsic vasculature of sessile juxtapapillary RCH and aids in its diagnosis. Tumors are better defined in OCTA than FFA due to the absence of leakage. However, FFA can identify nearly all the early tumors, but OCTA fails to image the peripheral tumors due to its smaller field and prolonged acquisition time. Technological advances and the development of wide-field OCTA in the future can be helpful in identifying all the unsuspected tumors in VHL disease. PMID- 29786011 TI - Nontraumatic subperiosteal orbital hemorrhage following upper gastrointestinal endoscopy. AB - Subperiosteal hemorrhages are typically the result of blunt orbital or facial trauma. Nontraumatic subperiosteal hemorrhages are uncommon and are usually attributed to increase in central venous pressure and bleeding disorders. Here, we report the case of a 38-year-old female who underwent an upper gastrointestinal (GI) endoscopy and developed bilateral nontraumatic subperiosteal hemorrhages that resolved with conservative treatment. Here, we discuss the source of bleeding and the mechanisms for the occurrence of orbital subperiosteal bleeds. GI surgeons and ophthalmologists should be sensitive to the possibility that orbital hemorrhage that can occur following endoscopy, especially when retching or gagging occurs during the procedure. PMID- 29786013 TI - Comment on: Limited vitrectomy in phacomorphic glaucoma. PMID- 29786012 TI - Navigation-guided optic canal decompression for traumatic optic neuropathy: Two case reports. AB - Two cases of traumatic optic neuropathy presented with profound loss of vision. Both cases received a course of intravenous corticosteroids elsewhere but did not improve. They underwent Navigation guided optic canal decompression via external transcaruncular approach, following which both cases showed visual improvement. Postoperative Visual Evoked Potential and optical coherence technology of Retinal nerve fibre layer showed improvement. These case reports emphasize on the role of stereotactic navigation technology for optic canal decompression in cases of traumatic optic neuropathy. PMID- 29786014 TI - Response to comment on: Limitied Anterior Vitrectomy in Phacomorphic glaucoma. PMID- 29786015 TI - Toilet pars plana vitrectomy for Surgical cases with shallow anterior chamber. PMID- 29786016 TI - Response to: Toilet Pars Plana Vitrectomy for surgical cases with shallow anterior chamber. PMID- 29786019 TI - Measuring situation awareness in medical education objective structured clinical examination guides. AB - Background: Medical errors are among the most prevalent and serious adverse events in health care. Lack of situation awareness (SA) is an important factor leading to such errors. SA can be understood using Endsley's three-tier model: level 1 is perception, level 2 is comprehension, and level 3 is projection. While there is extensive literature on the theory of SA, it is difficult to measure and quantify. The purpose of this pilot study was to measure, identify, and characterize SA in some medical objective structured clinical examination (OSCE) guides, including a 1st year National University of Ireland, Galway (NUIG) OSCE. Methods: Two independent observers analyzed two online OSCE guides and a 1st year OSCE examination using a self-developed tool. This tool was an inferential measure of SA. The guides were first qualitatively analyzed using NVivo and then quantitatively analyzed using Excel. Results: The results indicated strong internal validity and moderate inter-rater reliability. There was limited statistically significant variance between the observers. The NUIG OSCE had relatively the fewest relative observations of SA and the Geeky Medics OSCE Guide had relatively the most observations of SA. In all guides, Level 1 SA was observed more frequently than Level 2 or 3 SA. Discussion: SA is an important factor in clinical decision-making and patient safety. The challenging aspect is how to best teach and assess SA in medical education. Simulations, such as informative and/or summative OSCEs, are considered a valuable and safe way to do so. Inter-rater reliability can be improved using tool training sessions. PMID- 29786020 TI - Use of international foundations of medicine clinical sciences examination to evaluate students' performance in the local examination at the University of Sharjah, United Arab Emirates. AB - Background: Several medical schools around the world are moving away from isolated, locally developed in-house assessments to the introduction of external examinations into their curriculum. Although the objective varies, it is typically done to evaluate, audit, and compare students' performance to international standards. Similarly, the International Foundations of Medicine Clinical Sciences Examination (IFOM-CSE) was introduced in the College of Medicine at the University of Sharjah as an external assessment criterion in addition to the existing in-house assessments. The aim of this study was to compare the student performance in this newly introduced IFOM-CSE examination and the existing in-house final examination in the college. Methods: The scores of three consecutive final-year undergraduate medical student batches (2013-2015) who took both the IFOM-CSE and the existing in-house final examination were analyzed. Pearson correlation and one-way analysis of variance test were conducted using SPSS 22. Results: The students' scores in the IFOM-CSE and in the final examination prepared locally were highly correlated with Pearson correlation coefficients of 0.787 for batch 2013, 0.827 for batch 2014, and 0.830 for batch 2015 (P < 0.0005). Interestingly, while the mean scores of the IFOM-CSE among the three batches in the years 2013, 2014, and 2015 (475, 492, and 513, respectively) showed improvement with borderline significance (F[2226] = 2.73, P = 0.067), local examination scores showed a significant improvement during the study period (F[2277] = 52.87, P < 0.0005). Discussion: The findings of this study showed that students' scores in the local examination were consistently correlated with their scores in the IFOM-CSE over all the three batches. Thus, introduction of external examination can be an important evaluation tool to a comprehensive internal assessment system providing evidence of external validity. PMID- 29786021 TI - Developing and implementing a global emergency medicine course: Lessons learned from Rwanda. AB - Background: There is a growing demand by medical trainees for meaningful, short term global emergency medicine (EM) experiences. EM programs in high-income countries (HICs) have forged opportunities for their trainees to access this experience in low-and middle-income countries (LMICs). However, few programs in LMICs have created and managed such courses. As more LMICs establish EM programs, these settings are ideal for developing courses beneficial for all participants. We describe our experience of creating and implementing a short-term global EM course in Rwanda. Objectives: The objectives of this study were to (1) provide EM trainees from HICs with an opportunity to observe global clinical practice and to learn from local experts, (2) provide EM trainees from an LMIC with an opportunity to share their expert knowledge and skills with HIC trainees, (3) create a sustainable model for a short-term global EM course in an LMIC context. Methods: A global EM curriculum and course were developed in Rwanda, entitled EM in the Tropics Emergency Medicine in the Tropics (EMIT). The following topics were covered: EM systems development, public health, trauma/triage, pediatrics, disaster management, and tropical EM. A one-and two-week course program was created and implemented. Results: EMIT participants rotated through pediatric and adult EDs, Intensive Care Unit, trauma surgery, internal medicine, emergency medical services, and ultrasound training. Activities included bedside teaching, case presentations, ultrasound practice, group lectures, simulation and skills workshops, and a rotation to a district hospital. A total of 11 participants attended: six for both weeks and five for 1 week. The course raised $5000 USD, which was dedicated in full to sponsoring local EM residents to attend international conferences. Discussion: The EMIT course in Rwanda achieved its objectives of teaching and learning between all participants. Benefits of this in person experience for both visiting and local participants are clear in clinical, intercultural, and professional ways. Conclusion: Our experience of developing and implementing EMIT in Rwanda demonstrates that EM programs in LMICs can provide short-term global EM courses that are not only beneficial to all participants, but also logistically and financially sustainable. PMID- 29786022 TI - Personality traits predict a medical student preference to pursue a career in surgery. AB - Background: In this study, we examined the impact of personality traits, assessed with the psychopathic personality inventory revised version (PPI-R), on medical students' likelihood of selecting a surgical specialty. Methods: This is a cross sectional questionnaire-based study of 360 4th-year medical students at a single university. We used the PPI-R previously developed to evaluate "adaptive" traits within nonclinical (student) populations. Students were asked to express their specialty of choice. Medical specialties were categorized as surgical and nonsurgical. Logistic regression was used to identify predictors and appropriate adjustments were made for demographic factors. Results: The survey was completed by 335 out of 360 students. The prevalence of students aspiring to a surgical career was 23.6%. They exhibited higher PPI-R total score, self-centered impulsivity (SCI) factor score, Machiavellian egocentricity, social influence, and fearlessness content scale scores. Logistic regression showed that SCI score was a significant predictor for the likelihood of expressing interest toward a surgical career. Discussion: Our findings expand previous research on the usefulness of the nonclinical use of psychopathic personality traits to investigate career choice. PMID- 29786023 TI - Near peer-assisted learning to improve confidence for medical students' situational judgment tests. AB - Background: The situational judgment test (SJT) was introduced for all graduating United Kingdom medical students in 2013. Students have anxiety over time pressures and heavy weighting of a single examination. Aims: This study aimed to examine formal SJT preparation available, perceptions of a near peer-delivered course, and to measure improvement in students' confidence. Innovation: Foundation doctors ( first 2 years of postgraduate training) produced a "Situational Judgment Test Preparation Course" in November 2015. Methods: Feedback was collected via Likert scores rating teaching, a mock examination, and pre- and post-course confidence along with free-text responses. Delayed feedback was collected via an online survey. Results: Forty-four students completed the feedback. Seventy percent reported <2 h of university SJT preparation. There were significant post-course improvements in familiarity with structure, scoring system, knowledge and content, and overall SJT confidence (P < 0.05). Delayed feedback showed sustained improvement in familiarity with knowledge and content (P < 0.05). Qualitative analysis revealed themes of improved confidence, approachable tutors, and identifying question strategies. Discussion: Students perceived a lack of formal SJT preparation which was reflected in low pre-course confidence. Improvements in confidence may reflect a unique insight into how to approach the examination from those having recently undertaken it. PMID- 29786024 TI - Needs assessment of ophthalmology education for undergraduate medical students - A study from a medical college in South India. AB - Background: Adequate ophthalmic diagnostic and clinical skills are essential for practitioners in primary care settings as well as specialty care physicians. The objectives of this study were to assess the adequacy of ophthalmology teaching in undergraduate medical education and to evaluate the comfort of medical students in diagnosing common eye problems and performing ophthalmic skills. Methods: A questionnaire based, cross-sectional survey was conducted among third-year undergraduate students from a medical college in South India at the end of ophthalmology training from February 2014 to December 2014. The main outcome measures were hours of classroom-based instruction and clinical exposure to ophthalmology received by the students and their comfort level in diagnosing common eye problems and performing ophthalmic skills. Results: 134 students participated in the study. They had received an average of 96.2 +/- 5.9 and 112.5 +/- 11.3 hours of classroom and clinic-based instruction, respectively. The participants' comfort in diagnosing eye problems was satisfactory for cataract and eyelid disorders but not for ophthalmic emergencies. Only 45.5% had satisfactory knowledge in community ophthalmology. Respondents were more proficient in visual acuity testing (93.3%) and assessment of pupillary reaction (80.6%) than direct ophthalmoscopy (41%). Discussion: Undergraduate medical students from India received a greater amount of ophthalmology instruction compared to the International Council of Ophthalmology task force recommendations. Gaps in community ophthalmology and knowledge-skills discrepancies were noted. Review of curriculum, appropriate training resources, and effective teaching methods tailored towards primary care may be useful to improve the training. PMID- 29786026 TI - Sources of medical student stress. AB - Background: Key elements in the clinical practice of prevention, health and wellness are best cultivated in medical professionals during undergraduate medical training. This study explores students' self-assessed stress relative to gender, academic expectations, and level of medical training to guide development of targeted wellness interventions. Methods: In early 2012, undergraduate (M1-M4) students in four Southeastern U.S. allopathic medical schools were surveyed about health-related attitudes and behaviors. Results: A total of 575 students returned completed questionnaires. Students in the preclinical years (M1-M2), especially females, reported significantly higher stress levels. Academic expectations and satisfaction were also significantly implicated. Discussion: These findings highlight the general areas of potential concern regarding stressors associated with medical training. Future research should guide programmatic efforts to enhance students' overall health and wellness vis-a -vis curriculum, skills training, and support services. PMID- 29786025 TI - Resident perspectives on communication training that utilizes immersive virtual reality. AB - Background: Communication skills can be difficult to teach and assess in busy outpatient settings. These skills are important for effective counseling such as in cases of influenza vaccine hesitancy. It is critical to consider novel educational methods to supplement current strategies aimed at teaching relational skills. Methods: An immersive virtual reality (VR) curriculum on addressing influenza vaccine hesitancy was developed using Kern's six-step approach to curriculum design. The curriculum was meant to teach best-practice communication skills in cases of influenza vaccine hesitancy. Eligible participants included postgraduate level (PL) 2 and PL-3 pediatric residents (n = 24). Immediately following the curriculum, a survey was administered to assess residents' attitudes toward the VR curriculum and perceptions regarding the effectiveness of VR in comparison to other educational modalities. A survey was administered 1 month following the VR curriculum to assess trainee-perceived impact of the curriculum on clinical practice. Results: All eligible residents (n = 24) completed the curriculum. Ninety-two percent (n = 22) agreed or strongly agreed that VR simulations were like real-life patient encounters. Seventy-five percent (n = 18) felt that VR was equally effective to standardized patient (SP) encounters and less effective than bedside teaching (P < 0.001). At 1-month follow-up, 67% of residents (n = 16) agreed or strongly agreed that the VR experience improved how they counseled families in cases of influenza vaccine hesitancy. Discussion: An immersive VR curriculum at our institution was well received by learners, and residents rated VR as equally effective as SP encounters. As such, immersive VR may be a promising modality for communication training. PMID- 29786027 TI - Curriculum development for a module on noncommunicable diseases for the master of public health program. AB - Background: As the burden of noncommunicable diseases (NCDs) has been rising globally, various educational programs have introduced chronic disease epidemiology teaching, which is now a component of most of the Master of Public Health (MPH) programs. However, the process of curriculum development for these courses has not been adequately documented for use by educators planning such courses. Methods: A detailed process of curriculum development based on David Kern's six-step approach was undertaken for a 2-week course on NCDs, as part of the MPH program of a tertiary institution in South India. The processes were documented so that the method of curriculum development for such a course could be made available for educators across this field. Results: The course on NCDs was carried out over 73 learning hours (2 weeks) for a group of MPH students including medical, dental, allied health, and nursing graduates. Evaluation of the revised curriculum at the end of the 2 weeks revealed that mean scores for knowledge and confidence in skills increased by 50% (11.1-16.6, t-test, P < 0.001) and 79% (3.3-5.9, t-test, P = 0.002), respectively, from baseline scores. Discussion: The revised curriculum was effective in improving knowledge and confidence in epidemiological skills. The documented process of curricular development using standard methods if made publicly available can be of use to those involved in planning similar educational programs for students of public health. PMID- 29786028 TI - Evaluation of a distance learning academic support program for medical graduates during rural hospital service in India. AB - Background: Christian Medical College (CMC), Vellore, India, a tertiary care hospital, designed a year-long Fellowship in Secondary Hospital Medicine (FSHM) for CMC graduates, with the aim to support them during rural service and be motivated to consider practicing in these hospitals. The FSHM was a blend of 15 paper-based distance learning modules, 3 contact sessions, community project work, and networking. This paper reports on the evaluation of the FSHM program. Methods: The curriculum development process for the FSHM reflected the six-step approach including problem identification, needs assessment, formulating objectives, selecting educational strategies, implementation, and evaluation. Telephone interviews with students were conducted to determine if the program motivated them to consider working in smaller hospitals. Results: Qualitative data analysis showed that the program motivated the FSHM students to consider practicing in secondary hospitals by creating awareness of challenging opportunities and instilling confidence to provide good quality clinical care with limited resources. Discussion: We propose rural service for MBBS graduates, supported by a blend of on-site and distance education as a model for medical education. PMID- 29786029 TI - Academics anonymous: A medical student's 12-step guide to scholarly productivity. AB - An important aspect of academic medicine is publication in peer-reviewed journals and other media. Early scholarly productivity in medical school may jump-start a successful academic career. Topic choice, search methodology, writing strategies, mentorship, and collaboration are all fundamental to successful academic productivity. The authors reviewed the importance of instituting the germinal stages of scholarly productivity during medical training and created 12 steps for facilitating productive academic writing by students. PMID- 29786030 TI - Women deans' perceptions of the gender gap in American medical deanships. AB - Background: : Women account for 16% of deans of American medical schools. To investigate this gender gap, female deans were interviewed about the barriers facing women advancing toward deanships. Methods: The author conducted semi structured interviews with eight women deans. Interviews were analyzed using provisional coding and sub coding techniques. Results: Four main themes emerged during the interviews: (1) the role of relationships in personal and career development, (2) leadership challenges, (3) barriers between women and leadership advancement, and (4) recommendations for improvement. Recommendations included allocating resources, mentorship, career flexibility, faculty development, updating the criteria for deanships, and restructuring search committees. Discussion: The barriers identified by the deans are similar to those found in previous studies on female faculty and department chairs, suggesting limited improvement in gender equity progress. PMID- 29786031 TI - Health policy for health professions students: Building capacity for community advocacy in developing nations. PMID- 29786032 TI - Undergraduate research training: E-learning experience in Peru. PMID- 29786033 TI - A retrospective histological comparison of EUS-guided fine-needle biopsy using a novel franseen needle and a conventional end-cut type needle. AB - Background and Objectives: Recently, a 22G Franseen needle for EUS-guided fine needle biopsy (EUS-FNB) with three novel symmetric heels has been developed to adequately obtain a core tissue. Methods: All 38 consecutive patients with pancreatic masses who underwent EUS-FNB using a Franseen needle were investigated retrospectively to assess the efficacy and safety of EUS-FNB using the Franseen needle. Then, the EUS-FNB outcomes and histological assessments of the tissue obtained by EUS-FNB using the Franseen needle and EUS-FNA using the conventional end-cut type needle for each of the 30 pancreatic ductal adenocarcinoma cases were compared. Results: An accurate histological diagnosis of the Franseen needle was achieved with a mean of 2 passes in 97.4% of patients. Although the accurate histological diagnosis rate of pancreatic ductal adenocarcinoma was not significantly different (96.7% vs. 93.3%, P = 0.55), the mean number of passes in the Franseen needle was significantly less than that in the conventional needle (2.1 +/- 0.4 vs. 3.2 +/- 0.8, P < 0.001). The presence of desmoplastic fibrosis with neoplastic cellular elements and venous invasion were significantly higher (96.7% vs. 40.0%, P < 0.001 and 23.3% vs. 0%, P < 0.01, respectively) and the amount of obtained tissue was significantly larger with the Franseen needle (2.13 mm2 vs. 0.45 mm2, P < 0.001). Conclusions: EUS-FNB using the Franseen needle enables the acquisition of a larger amount of tissue sample and achieves an accurate histological diagnosis with a smaller number of passes than the conventional end-cut type needle. PMID- 29786034 TI - Mixed ductal-neuroendocrine carcinoma with unique intraductal growth in the main pancreatic duct. PMID- 29786035 TI - Initial report of transesophageal EUS-guided intraparenchymal lung mass core biopsy: Findings and outcomes in two cases. AB - EUS is most commonly used to evaluate and sample lesions of the abdomen but has only been used on rare occasions to evaluate and sample lung lesions. Prior reported cases of EUS sampling of lung lesions were performed by fine-needle aspiration. We present what is believed to be the first reported cases of EUS guided core biopsy of intraparenchymal lung lesions through two separate case reports. Both patients had the upper lobe lesions not amenable to bronchoscopy or endobronchial ultrasound, and both patients underwent core biopsy without adverse event. This report of two cases shows that EUS-guided core biopsy of intraparenchymal lung lesions is technically possible and may not necessarily result in adverse events such as hemorrhage, pneumothorax, or infection. PMID- 29786036 TI - Overall Blastocyst Quality, Trophectoderm Grade, and Inner Cell Mass Grade Predict Pregnancy Outcome in Euploid Blastocyst Transfer Cycles. AB - Background: Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization (IVF) therapy, it is not yet clear which blastocyst morphological parameters best predict the outcomes of single blastocyst transfer. In addition, most of the previous studies did not exclude the effect of embryo aneuploidy on blastocysts transfer. Thus, the present study investigated the predictive value of various parameters on the pregnancy outcomes achieved via the transfer of frozen euploid blastocysts. Methods: The study retrospectively analyzed 914 single euploid blastocyst transfer cycles that were performed at the Peking University Third Hospital Reproductive Medical Center between June 2011 and May 2016. The expansion, trophectoderm (TE), and inner cell mass (ICM) quality of the blastocysts were assessed based on blastocyst parameters, and used to differentiate between "excellent", "good", "average", and "poor"-quality embryos. The relationship between these embryo grades and the achieved pregnancy outcomes was then analyzed via the Chi-square and logistic regression tests. Results: For embryo grades of excellent, good, average and poor, the clinical pregnancy rates were 65.0%, 59.3%, 50.3% and 33.3%, respectively; and the live-birth rates were 50.0%, 49.7%, 42.3% and 25.0%, respectively. Both the clinical pregnancy rate (chi2 = 21.28, P = 0.001) and live-birth rate (chi2 = 13.50, P < 0.001) increased with the overall blastocyst grade. Both rates were significantly higher after the transfer of a blastocyst that exhibited either an A-grade or B-grade TE, and similarly, an A grade ICM, than after the transfer of a blastocyst that exhibited a C-grade TE and/or ICM. The degree of blastocyst expansion had no apparent effect on the clinical pregnancy or live-birth rate. All odds ratio were adjusted for patient age, body mass index, length (years) of infertility history, and infertility type. Conclusions: A higher overall euploid blastocyst quality is shown to correlate most strongly with optimal pregnancy outcomes. The study thus supports the use of the described TE and ICM morphological grades to augment current embryo selection criteria. PMID- 29786037 TI - Preliminary Outcome of Individualized Abdominoperineal Excision for Locally Advanced Low Rectal Cancer. AB - Background: The introduction of individualized abdominoperineal excision (APE) may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer. Methods: Fifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin (CRM) involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0. Results: Fifty (89%) patients received preoperative chemoradiotherapy: 51 (91%) patients were treated with the sacrococcyx preserved; 27 (48%) patients with the levator ani muscle partially preserved bilaterally; 20 (36%) patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 (13%) patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 (4%) patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction (12%), perineal wound complications (13%), urinary retention (7%), and chronic perineal pain (5%). A positive CRM was demonstrated in 3 (5%) patients, and intraoperative perforations occurred in 2 (4%) patients. On multiple logistic regression analysis, longer operative time (P = 0.032) and more intraoperative blood loss (P = 0.006) were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow up of 53 months (range: 30-74 months). Conclusion: With preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes. PMID- 29786038 TI - A Predictive Model for Estimation Risk of Proliferative Lupus Nephritis. AB - Background: Lupus nephritis (LN) is classified by renal biopsy into proliferative and nonproliferative forms, with distinct prognoses, but renal biopsy is not available for every LN patient. The present study aimed to establish an alternate tool by building a predictive model to evaluate the probability of proliferative LN. Methods: In this retrospective cohort with biopsy-proven LN, 382 patients in development cohort, 193 in internal validation cohort, and 164 newly diagnosed patients in external validation cohort were selected. Logistic regression model was established, and the concordance statistics (C-statistics), Akaike information criterion (AIC), integrated discrimination improvement, Hosmer Lemeshow test, and net reclassification improvement were calculated to evaluate the performance and validation of models. Results: The prevalence of proliferative LN was 77.7% in the whole cohort. A model, including age, gender, systolic blood pressure, hemoglobin, proteinuria, hematuria, and serum C3, performed well on good-of-fit and discrimination in the development chohort to predict the risk of proliferative LN (291 for AIC and 0.84 for C-statistics). In the internal and external validation cohorts, this model showed good capability for discrimination and calibration (0.84 and 0.82 for C-statistics, and 0.99 and 0.75 for P values, respectively). Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes. PMID- 29786039 TI - Role of Soluble ST2 Levels and Beta-Blockers Dosage on Cardiovascular Events of Patients with Unselected ST-Segment Elevation Myocardial Infarction. AB - Background: Serum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown. Methods: A total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low <=56 ng/ml) and final therapeutic BB dose (high >=47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI. Results: Baseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI. Conclusions: High baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology. PMID- 29786041 TI - Fixation versus Excision of Osteochondral Fractures after Patellar Dislocations in Adolescent Patients: A Retrospective Cohort Study. AB - Background: Patellar dislocation is one of the most common knee injuries in the adolescent population. It is often combined with osteochondral fracture. The purpose of this study was to compare the outcomes between fixation and excision of osteochondral fractures not involving the bearing surface in adolescent patients with patellar dislocations. Methods: Patients who underwent surgery for osteochondral fracture following patellar dislocation in our institution from 2007 to 2014 were retrospectively evaluated. Visual analog scale (VAS) of pain and the International Knee Documentation Committee (IKDC) form were used to assess knee pain and function at follow-up. Patient satisfaction was evaluated. Differences in the values of variables among groups were assessed using t-test if equal variance or Mann-Whitney U-test if not equal variance. The Pearson's Chi square test was applied for dichotomous variables if expected frequency was >5 or Fisher's exact test was applied if not. A value of P < 0.05 was considered statistically significant. Results: Forty-three patients were included, with the average age of 14.1 +/- 2.3 (range, 9.0-17.0) years. Nineteen underwent fixation of osteochondral fractures and 24 did not. The average follow-up time was 28 +/- 10 months. There was no significant difference in age, gender, follow-up time, causes of injury, times of dislocation, and location of osteochondral fracture between fixation and excision groups. The fixation group had a significantly longer surgery time (82 +/- 14 min) and larger size of osteochondral fracture (2.30 +/- 0.70 cm2) than the excision group (43 +/- 10 min, 1.88 +/- 0.62 cm2, respectively, t = 10.77, P < 0.01 and t = 0.84, P < 0.05). At the last follow-up, the average IKDC score in the fixation group (82.52 +/- 8.71) was significantly lower than that in the excision group (89.51 +/- 7.19, t = 2.65, P < 0.01). There was no significant difference in VAS of pain and patients' satisfaction. There were 7 (16%) patients with recurrent dislocation. Conclusion: Excision of osteochondral fractures has equivalent or better outcomes compared to fixation in adolescent patients with patellar dislocations when these fractures do not involve the bearing surface. PMID- 29786042 TI - Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation. AB - Background: Immunosuppressive agents are still inefficient in preventing biopsy proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR. Methods: We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC)0-12h and Tac C0were measured at the 1st week and the 1st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression. Results: The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC0-12h at the 1st week posttransplant was found in BPAR recipients (38.42 +/- 8.37 vs. 50.64 +/- 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUC0-12hlevel was <30 mg.h-1.L-1 at the 1st week (15.0% vs. 44.4%) or the Tac C0was <4 ng/ml at the 1st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC0-12h at the 1st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C0at the 1st month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05). Conclusions: Low-level exposure of MPA and Tac C0in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC0-12h <30 mg.h-1.L-1 and Tac C0 <4 ng/ml should be avoided in the first few weeks after transplantation. PMID- 29786040 TI - Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood. AB - Background: Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy. Methods: Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses. Results: HLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion: MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated. PMID- 29786043 TI - Risk Factors for Recurrence of Ovarian Endometriosis in Chinese Patients Aged 45 and Over. AB - Background: When considering the issue of recurrence, perimenopausal women may have more dilemma during management comparing with young women, for example, whether to retain the uterus and ovary during surgery, whether it is necessary to add adjuvant medicine treatment after operation, and there is no evidence for reference about using of gonadotropin-releasing hormone agonist. This study aimed to study the risk factors for the recurrence of ovarian endometriosis (EM) in patients aged 45 and over. Methods: This is a retrospective nested case-control study. We reviewed the medical records of patients aged over 45 years who underwent surgical treatments for ovarian EM from 1994 to 2014, in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences. By following up to January 2016, 45 patients were found to have relapses and regarded as the recurrence group. The patients with no recurrence during the same follow-up period were randomly selected by the ratio of 1:4 as the nonrecurrence group (180 patients in total). Stratified Cox regression was used to analyze the risk factors of the recurrence. Results: Univariate analysis showed that there was a significant difference in the postoperative treatment (the percentage of patients who received postoperative treatment in non-recurrence group and recurrence group, 23.9% vs. 40.0%, chi2 = 4.729, P = 0.030) and ovarian preservation (the percentage of patients who received surgery of ovarian preservation in non recurrence group and recurrence group, 25.0 % vs. 44.4%, chi2 = 19.462, P < 0.001) between the nonrecurrence group and the recurrence group. There was no correlation between recurrence and the following factors including patient's age, menarche age, gravidity, parity, CA125 level, ovarian lesions, menopausal status, combined benign gynecological conditions (such as myoma and adenomyoma) and endometrial abnormalities, and surgical approach or surgical staging (all P > 0.05). Multivariate analysis indicated that whether to retain the ovary was the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM (odds ratio: 5.594, 95% confidence interval: 1.919-16.310, P = 0.002). Conclusion: Ovarian preservation might be the only independent risk factor of recurrence for patients aged 45 years and over with ovarian EM. PMID- 29786045 TI - Corrigendum: Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study. AB - [This corrects the article DOI: 10.4103/0366-6999.229904]. PMID- 29786044 TI - Prognostic Value of Model for End-Stage Liver Disease Incorporating with Serum Sodium Score for Development of Acute Kidney Injury after Liver Transplantation. AB - Background: Contribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT. Methods: Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI. Results: The prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively. Conclusions: We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score. PMID- 29786046 TI - Effect of Double-Balloon Enteroscopy on Diagnosis and Treatment of Small-Bowel Diseases. AB - Background: The diagnosis and treatment of small-bowel diseases is clinically difficult. The purpose of this study was to evaluate the diagnostic and therapeutic value of double-balloon enteroscopy in small-bowel diseases. Methods: The history and outcomes of 2806 patients who underwent double-balloon enteroscopy from July 2004 to April 2017 were reviewed, which included 562 patients with obscure digestive tract bleeding, 457 patients with obscure diarrhea, 930 patients with obscure abdominal pain, 795 patients with obscure weight loss, and 62 patients with obscure intestinal obstruction. Examinations were performed through the mouth and/or anus according to the clinical symptoms and abdominal images. If a lesion was not detected through one direction, examination through the other direction was performed as necessary. Eighty-four patients with small-bowel polyps, 26 with intestinal obstruction caused by enterolith, and 18 with bleeding from Dieulafoy's lesions in the small intestine were treated endoscopically. Results: A total of 2806 patients underwent double balloon enteroscopy, and no serious complications occurred. An endoscopic approach through both the mouth and anus was used in 212 patients. Lesions were detected in 1696 patients, with a detection rate of 60.4%; the rates for obscure digestive tract bleeding, diarrhea, abdominal pain, weight loss, and intestinal obstruction were 85.9% (483/562), 73.5% (336/457), 48.2% (448/930), 49.1% (390/795), and 62.9% (39/62), respectively. For patients with small-bowel polyps who underwent endoscopic therapy, no complications such as digestive tract bleeding and perforation occurred. Intestinal obstruction with enteroliths was relieved with endoscopic lithotripsy. Among the 18 patients with bleeding from small-bowel Dieulafoy's lesions, 14 patients were controlled with endoscopic hemostasis. Conclusion: Double-balloon enteroscopy is useful for diagnosing and treating some small-bowel disease. PMID- 29786047 TI - Establishment of a Quantitative Medical Technology Evaluation System and Indicators within Medical Institutions. AB - Background: The development and application of medical technologies reflect the medical quality and clinical capacity of a hospital. It is also an effective approach in upgrading medical service and core competitiveness among medical institutions. This study aimed to build a quantitative medical technology evaluation system through questionnaire survey within medical institutions to perform an assessment to medical technologies more objectively and accurately, and promote the management of medical quality technologies and ensure the medical safety of various operations among the hospitals. Methods: A two-leveled quantitative medical technology evaluation system was built through a two-round questionnaire survey of chosen experts. The Delphi method was applied in identifying the structure of evaluation system and indicators. The judgment of the experts on the indicators was adopted in building the matrix so that the weight coefficient and maximum eigenvalue (lambda max), consistency index (CI), and random consistency ratio (CR) could be obtained and collected. The results were verified through consistency tests, and the index weight coefficient of each indicator was conducted and calculated through analytical hierarchy process. Results: Twenty-six experts of different medical fields were involved in the questionnaire survey, 25 of whom successfully responded to the two-round research. Altogether, 4 primary indicators (safety, effectiveness, innovativeness, and benefits), as well as 13 secondary indicators, were included in the evaluation system. The matrix is built to conduct the lambda max, CI, and CR of each expert in the survey, and the index weight coefficients of primary indicators were 0.33, 0.28, 0.27, and 0.12, respectively, and the index weight coefficients of secondary indicators were conducted and calculated accordingly. Conclusions: As the two-round questionnaire survey of experts and statistical analysis were performed and credibility of the results was verified through consistency evaluation test, the study established a quantitative medical technology evaluation system model and assessment indicators within medical institutions based on the Delphi method and analytical hierarchy process. Moreover, further verifications, adjustments, and optimizations of the system and indicators will be performed in follow-up studies. PMID- 29786048 TI - Cardiac Hypertrophy is Positively Regulated by MicroRNA-24 in Rats AB - Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 +/- 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. Results: The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = -2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression. PMID- 29786049 TI - Lipoxin A4 Ameliorates Lipopolysaccharide-Induced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1. AB - Background: Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. Methods: A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-alpha/gamma. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-alpha expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression. Results: The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 +/- 0.063 vs. 0.878 +/- 0.083, P = 0.040) and ENaC-alpha expression (treatment vs. control, 0.458 +/- 0.038 vs. 0.711 +/- 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 +/- 0.023 vs. 0.726 +/- 0.020, P = 0.001) and ENaC-alpha (treatment vs. control, 0.236 +/- 0.021 vs. 0.814 +/- 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 +/- 0.024 vs. 1.046 +/- 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4. Conclusion: Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression. PMID- 29786052 TI - Function of Rho GTPase Activating Protein 11A in Tumors. PMID- 29786050 TI - Diagnostic Performance of Intestinal Fusobacterium nucleatum in Colorectal Cancer: A Meta-Analysis. AB - Background: Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. Methods: An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized. Results: Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64 0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00 22.00). Conclusion: Intestinal F. nucleatum is a valuable marker for CRC diagnosis. PMID- 29786053 TI - Pancreaticojejunal Bridge Stent Internal Drainage as a Safe Reconstruction Technique after Middle Segmental Pancreatic Resection. PMID- 29786054 TI - Molecular Investigation of an Anthrax Epidemic in Guizhou Province, China. PMID- 29786051 TI - Urinary Extracellular Vesicle: A Potential Source of Early Diagnostic and Therapeutic Biomarker in Diabetic Kidney Disease. AB - Objective: Diabetic kidney disease (DKD) has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles (uEVs) contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD. Data Sources: This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords: "Diabetic kidney disease", "Extracellular vesicle", and "Urine". Study Selection: Relevant articles were carefully reviewed, with no exclusions applied to the study design and publication type. Results: There is no "gold standard" technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD. Conclusion: Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD. PMID- 29786055 TI - Successful Ablation of Moderator Band-Originated Ventricular Tachycardia at Its Ventricle Insertion Sites. PMID- 29786056 TI - Cavernous Transformation of the Portal Vein Secondary to Cholecystolithiasis. PMID- 29786057 TI - Pulmonary Hypertension in Glycogen Storage Disease Type II. PMID- 29786058 TI - Non-Hodgkin's Lymphoma: An Important Differential Diagnosis in Inflammatory Bowel Disease. PMID- 29786059 TI - Recurrent Cardiac Tamponade from Right Atrial Angiosarcoma. PMID- 29786060 TI - Super-Flexible Through-the-Scope Self-Expandable Metallic Stent Insertion for the Management of Malignant Tortuous Hepatic or Splenic Flexure Colonic Obstruction. PMID- 29786061 TI - Leprosy in Children: Needs for Active Intervention. PMID- 29786062 TI - Reply to the Comments from Readers. PMID- 29786063 TI - Induction of prolonged natural lifespans in mice exposed to acoustic environmental enrichment. AB - We investigated the effect of acoustic environmental enrichment (EE) on the lifespans and behaviours of mice to the end of their natural lifespan in different acoustic environments. Acoustic EE induced a significantly prolonged natural lifespan (nearly 17% longer) and was associated with increased voluntary movements. However, no correlation between lifespan and voluntary movements was detected, suggesting that increased voluntary movements are not a primary cause of lifespan prolongation. Analyses of individual differences in lifespan demonstrated that lifespan extension induced by acoustic EE could be related to changes in social relationships (e.g., reduction of social conflict) among individuals kept within a cage. Therefore, an acoustic component may be an important factor inducing the positive effects of EE. PMID- 29786064 TI - Fabrication of aluminum alloy functionally graded material using directional solidification under an axial static magnetic field. AB - Aluminum alloy in situ functionally graded materials (FGMs) have been successfully fabricated using directional solidification under an axial static magnetic field. Al-Zn, Al-Ni and Al-Cu alloys with a hypereutectic composition were selected to produce FGMs. Experimental results show that the graded composition of the primary phases (i.e., Zn, Al3Ni and Al2Cu) is obvious along the longitudinal section of the sample. The graded composition of the primary phases could be controlled by the value of the magnetic field, growth rate and temperature gradient. A proposed model and simulations are carried out to explain the origin of the graded composition of the primary phases in FGMs during directional solidification under an axial static magnetic field. It should be attributed to the combined actions of heavier species migration under gravity force and thermoelectric (TE) magnetic convection under magnetic field. Furthermore, it can be found that the magnetic field can induce the columnar FGMs to change into equiaxed FGMs. This work not only presents a new approach to fabricate FGMs using the directional solidification under an axial static magnetic field but also deeply understands the effect of the solute migration and temperature distribution on the crystal growth during directional solidification. PMID- 29786065 TI - Real-time precise point positioning-based zenith tropospheric delay for precipitation forecasting. AB - GPS-based Zenith Tropospheric Delay (ZTD) estimation should be easily obtained in a cost-effective way, however, the most previous studies focus on post-processed ZTD estimates using satellite orbit and clock products with at least 3-9 hours latency provided by International GNSS Service (IGS), which limits the GNSS meteorological application for nowcasting. With the development of IGS's real time pilot project (RTPP), this limitation was removed by April, 2013 as real time satellite orbit and clock products can be obtained on-line. In this paper, on the one hand, the GPS-derived ZTD estimation was evaluated using the IGS final and real-time satellite products based on independently developed PPP software. On the other hand, the analysis of the time series of GPS-derived ZTD by least square fitting of a broken line tendency for a full year of observations, and a forecasting method for precipitation is proposed based on the ZTD slope in the ascending period. The agreement between ZTD slope and the ground rainfall records suggested that the proposed method is useful for the assisted forecasting, especially for short-term alarms. PMID- 29786067 TI - Disrupting reconsolidation: memory erasure or blunting of emotional/motivational value? AB - When memories are retrieved they become labile, and subject to alteration by a process known as reconsolidation. Disruption of memory reconsolidation decreases the performance of learned responses, which is often attributed to erasure of the memory; in the case of Pavlovian learning, to a loss of the association between a conditioned stimulus (CS) and unconditioned stimulus (US). However, an alternative interpretation is that disrupting reconsolidation does not erase memories, but blunts their emotional/motivational impact. It is difficult to parse the predictive vs. emotional/motivational value of CSs in non-human animals, but studies on variation in the form of conditioned responses (CRs) in a Pavlovian conditioned approach task suggest a way to do this. In this task a lever-CS paired with a food reward (US) acquires predictive value in all rats, but is attributed with emotional/motivational value to a greater extent in some rats (sign-trackers) than others (goal-trackers). We report that the post retrieval administration of propranolol selectively attenuates a sign-tracking CR, and the associated neural activation of brain "motive circuits", while having no effect on conditioned orienting behavior in sign-trackers, or on goal-tracking CRs evoked by either a lever-CS or a tone-CS. We conclude that the disruption of reconsolidation by post-retrieval propranolol degrades the emotional/motivational impact of the CS, required for sign-tracking, but leaves the CS-US association intact. The possibility that post-retrieval interventions can reduce the emotional/motivational aspects of memories, without actually erasing them, has important implications for treating maladaptive memories that contribute to some psychiatric disorders. PMID- 29786068 TI - Mitochondrial PIP3-binding protein FUNDC2 supports platelet survival via AKT signaling pathway. AB - Platelets undergo apoptosis in response to a variety of stimuli in the circulation. Mitochondria in platelets are essential for their apoptosis. Specifically, pro-survival protein BCL-xL on mitochondria is the key regulator of platelet lifespan. Here we identify an outer mitochondrial membrane protein FUNDC2 for platelet survival. FUNDC2 knockout mice carrying excessively apoptotic platelets exhibit thrombocytopenia in response to hypoxia. Mechanistically, FUNDC2 binds the lipid PIP3 via its unique, highly conserved N-terminal motif. FUNDC2 deficiency abrogates the phosphorylation of AKT and its substrate BAD in a PIP3/PI3K-dependent manner, which suppresses BCL-xL. Indeed, FUNDC2 deficiency shortens the platelet lifespan under stress. Thus, this FUNDC2/AKT/BCL-xL axis signifies a balance between platelet survival and apoptosis at the single organelle level and provides new insight for platelet-related diseases as well. PMID- 29786069 TI - VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression. AB - Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus. FAK inhibition enabled kaiso to suppress the expression of its target genes and enhanced kaiso recruitment to KBS containing promoters. Finally we have found that ablation of kaiso-repressed genes WNT11 and CCDN1 abolished VM. Thus, identification of pVEC as a component of the kaiso transcriptional complex establishes a molecular paradigm that links FAK-dependent phosphorylation of VEC as a major mechanism by which ectopical VEC expression exerts its function in VM. PMID- 29786066 TI - Repeated social defeat-induced neuroinflammation, anxiety-like behavior and resistance to fear extinction were attenuated by the cannabinoid receptor agonist WIN55,212-2. AB - Psychosocial stress contributes to the development of psychiatric disorders. Repeated social defeat (RSD) is a murine stressor that causes a release of inflammatory monocytes into circulation. Moreover, RSD-induced anxiety-like behavior is dependent on the recruitment of these monocytes to the brain. Activation of the endocannabinoid (ECB) system may modulate both neuroendocrine and inflammatory responses mediated by stress. Therefore, we hypothesized that a cannabinoid receptor agonist would attenuate RSD-induced inflammation, anxiety, and stress sensitization. To test this hypothesis, mice received an injection of the synthetic cannabinoid1/2 receptor agonist, WIN55,212-2 (WIN; 1 mg/kg, intraperitoneally) daily for six consecutive days, 30 min before each exposure to RSD. Anxiety-like behavior, immune activation, neuroinflammation, and microglial reactivity were determined 14 h after RSD. RSD-induced anxiety-like behavior in the open field and in the EPM was reversed by WIN55,212-2. Moreover, WIN55,212-2 reduced the accumulation of inflammatory monocytes in circulation and brain after RSD and attenuated RSD-induced interleukin-1beta (IL-1beta) messenger RNA (mRNA) expression in microglia/macrophages. Increased ex vivo reactivity of microglia/monocytes to lipopolysaccharides (LPS) after RSD was also attenuated by WIN55,212-2. Next, fear expression, extinction, and recall were evaluated 24 and 48 h, respectively, after contextual fear conditioning, which took place 7 days after RSD. Here, RSD caused prolonged fear expression and impaired fear extinction recall, which was associated with increased IL-1beta mRNA in the brain. Moreover, these stress-induced effects were reversed by WIN55,212-2. In conclusion, activation of cannabinoid receptors limited the immune and neuroinflammatory responses to RSD and reversed the short-term and long-term behavioral deficits associated with RSD. PMID- 29786070 TI - Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2. AB - Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells. In naturally aged mice treated with MitoTam for 4 weeks, we observed a significant decrease of senescence markers in all tested organs compared to non-treated animals. Mechanistically, we found that the susceptibility of senescent cells to MitoTam is linked to a very low expression level of adenine nucleotide translocase-2 (ANT2), inherent to the senescent phenotype. Restoration of ANT2 in senescent cells resulted in resistance to MitoTam, while its downregulation in non senescent cells promoted their MitoTam-triggered elimination. Our study documents a novel, translationally intriguing role for an anticancer agent targeting mitochondria, that may result in a new strategy for the treatment of age-related diseases and senescence-associated pathologies. PMID- 29786072 TI - MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. AB - Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Specifically, NLRP3 deficiency significantly reduces motor dysfunctions and dopaminergic neurodegeneration of MPTP-treated mice. Furthermore, NLRP3 deficiency abolishes MPTP-induced microglial recruitment, interleukin-1beta production and caspase-1 activation in the SN of mouse brain. In primary microglia and mixed glial cell cultures, MPTP/ATP treatment promotes the robust assembly and activation of the NLRP3 inflammasome via producing mitochondrial reactive oxygen species. Consistently, 1-methyl-4-phenyl-pyridinium (MPP+) induces NLRP3 inflammasome activation in the presence of ATP or nigericin treatment in mouse bone-marrow-derived macrophages. These findings reveal a novel priming role of neurotoxin MPTP or MPP+ for NLRP3 activation. Subsequently, NLRP3 inflammasome-active microglia induces profound neuronal death in a microglia neuron co-culture model. Furthermore, Cx3Cr1CreER-based microglia-specific expression of an active NLRP3 mutant greatly exacerbates motor deficits and dopaminergic neuronal loss of MPTP-treated mice. Taken together, our results indicate that microglial NLRP3 inflammasome activation plays a pivotal role in the MPTP-induced neurodegeneration in PD. PMID- 29786071 TI - Dopamine D2 receptor restricts astrocytic NLRP3 inflammasome activation via enhancing the interaction of beta-arrestin2 and NLRP3. AB - Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1beta (IL-1beta) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. beta-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system. However, the role of Drd2 in astrocytic NLRP3 inflammasome activation and subsequent IL-1beta production remains unclear. In the present study, we used 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine-induced PD mouse model to investigate whether Drd2 could suppress astrocytic NLRP3 inflammasome activation. We showed that Drd2 agonist inhibited NLRP3 inflammasome activation, evidenced by decreased caspase-1 expression and reduced IL-1beta release in the midbrain of wild type mice. The anti-inflammasome effect of Drd2 was abolished in beta-arrestin2 knockout and beta-arrestin2 small interfering RNA-injected mice, suggesting a critical role of beta-arrestin2 in Drd2-regulated NLRP3 inflammasome activation. We also found that Drd2 agonists suppressed the upregulation of caspase-1 and IL-1beta expression in primary cultured mouse astrocytes in response to the activation of NLRP3 inflammasome induced by lipopolysaccharide plus adenosine triphosphate. Furthermore, we demonstrated that beta-arrestin2 mediated the inhibitory effect of Drd2 on NLRP3 inflammasome activation via interacting with NLRP3 and interfering the inflammasome assembly. Collectively, our study illustrates that astrocytic Drd2 inhibits NLRP3 inflammasome activation through a beta-arrestin2 dependent mechanism, and provides a new strategy for treatment of PD. PMID- 29786073 TI - Integrin alpha6beta4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues. AB - Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin beta4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin beta4 at tyrosine residue 1510, leading to activation of the integrin alpha6beta4-Src-AKT signaling pathway. We further reveal that the IR-induced phosphorylation of integrin beta4 is regulated by the cholesterol content and membrane fluidity. We also find that IR-induced p53-caspase signaling is independent of integrin alpha6beta4-Src-AKT signaling. Finally, we show that siRNA- or inhibitor-mediated blockade of integrin alpha6beta4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. On the basis of our finding that, integrin alpha6beta4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy. PMID- 29786074 TI - Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis. AB - Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and maintains the expression of MLKL and one or more unknown effectors above a critical threshold to allow for MLKL oligomerization and cell death. Finally, we found that elevated IFN-signaling in systemic lupus erythematosus (SLE) augments necroptosis, providing a link between pathological IFN and tissue damage during autoimmunity. PMID- 29786075 TI - TP53 gain-of-function mutation promotes inflammation in glioblastoma. AB - Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations. Here we demonstrate that a TP53 GOF mutation promotes inflammation in GBM. Ectopic expression of a TP53 GOF mutant induced transcriptomic changes, which resulted in enrichment of gene signatures related to inflammation and chemotaxis. Bioinformatics analyses revealed that a gene signature, upregulated by the TP53 GOF mutation, is associated with progression and shorter overall survival in GBM. We also observed significant correlations between the TP53 GOF mutation signature and inflammation in the clinical database of GBM and other cancers. The TP53 GOF mutant showed upregulated C-C motif chemokine ligand 2 (CCL2) and tumor necrosis factor alpha (TNFA) expression via nuclear factor kappa B (NFkappaB) signaling, consequently increasing microglia and monocyte-derived immune cell infiltration. Additionally, TP53 GOF mutation and CCL2 and TNFA expression correlated positively with tumor associated immunity in patients with GBM. Taken together, our findings suggest that the TP53 GOF mutation plays a crucial role in inflammatory responses, thereby deteriorating prognostic outcomes in patients with GBM. PMID- 29786076 TI - c-Myc inhibits myoblast differentiation and promotes myoblast proliferation and muscle fibre hypertrophy by regulating the expression of its target genes, miRNAs and lincRNAs. AB - The transcription factor c-Myc is an important regulator of cellular proliferation, differentiation and embryogenesis. While c-Myc can inhibit myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that c-Myc does not only inhibits myoblast differentiation but also promotes myoblast proliferation and muscle fibre hypertrophy. By performing chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we identified the genome-wide binding profile of c-Myc in skeletal muscle cells. c Myc achieves its regulatory effects on myoblast proliferation and differentiation by targeting the cell cycle pathway. Additionally, c-Myc can regulate cell cycle genes by controlling miRNA expression of which dozens of miRNAs can also be regulated directly by c-Myc. Among these c-Myc-associated miRNAs (CAMs), the roles played by c-Myc-induced miRNAs in skeletal muscle cells are similar to those played by c-Myc, whereas c-Myc-repressed miRNAs play roles that are opposite to those played by c-Myc. The cell cycle, ERK-MAPK and Akt-mediated pathways are potential target pathways of the CAMs during myoblast differentiation. Interestingly, we identified four CAMs that can directly bind to the c-Myc 3' UTR and inhibit c-Myc expression, suggesting that a negative feedback loop exists between c-Myc and its target miRNAs during myoblast differentiation. c-Myc also potentially regulates many long intergenic noncoding RNAs (lincRNAs). Linc-2949 and linc-1369 are directly regulated by c-Myc, and both lincRNAs are involved in the regulation of myoblast proliferation and differentiation by competing for the binding of muscle differentiation-related miRNAs. Our findings do not only provide a genome-wide overview of the role the c Myc plays in skeletal muscle cells but also uncover the mechanism of how c-Myc and its target genes regulate myoblast proliferation and differentiation, and muscle fibre hypertrophy. PMID- 29786077 TI - Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility. AB - Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells. PMID- 29786079 TI - Dissection of DNA double-strand-break repair using novel single-molecule forceps. AB - Repairing DNA double-strand breaks (DSBs) by nonhomologous end joining (NHEJ) requires multiple proteins to recognize and bind DNA ends, process them for compatibility, and ligate them together. We constructed novel DNA substrates for single-molecule nanomanipulation, allowing us to mechanically detect, probe, and rupture in real-time DSB synapsis by specific human NHEJ components. DNA-PKcs and Ku allow DNA end synapsis on the 100 ms timescale, and the addition of PAXX extends this lifetime to ~2 s. Further addition of XRCC4, XLF and ligase IV results in minute-scale synapsis and leads to robust repair of both strands of the nanomanipulated DNA. The energetic contribution of the different components to synaptic stability is typically on the scale of a few kilocalories per mole. Our results define assembly rules for NHEJ machinery and unveil the importance of weak interactions, rapidly ruptured even at sub-picoNewton forces, in regulating this multicomponent chemomechanical system for genome integrity. PMID- 29786078 TI - Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy. AB - Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8+ and CD4+ T cells to suppress melanoma progression, and combining NRF2 inhibition with anti PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment. PMID- 29786081 TI - Distinct learning-induced changes in stimulus selectivity and interactions of GABAergic interneuron classes in visual cortex. AB - How learning enhances neural representations for behaviorally relevant stimuli via activity changes of cortical cell types remains unclear. We simultaneously imaged responses of pyramidal cells (PYR) along with parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) inhibitory interneurons in primary visual cortex while mice learned to discriminate visual patterns. Learning increased selectivity for task-relevant stimuli of PYR, PV and SOM subsets but not VIP cells. Strikingly, PV neurons became as selective as PYR cells, and their functional interactions reorganized, leading to the emergence of stimulus-selective PYR-PV ensembles. Conversely, SOM activity became strongly decorrelated from the network, and PYR-SOM coupling before learning predicted selectivity increases in individual PYR cells. Thus, learning differentially shapes the activity and interactions of multiple cell classes: while SOM inhibition may gate selectivity changes, PV interneurons become recruited into stimulus-specific ensembles and provide more selective inhibition as the network becomes better at discriminating behaviorally relevant stimuli. PMID- 29786082 TI - mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors. AB - The mechanistic target of rapamycin complex 1 (mTORC1) has been reported to be necessary for metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). Here we found that mTORC1-deficient mice exhibit normal hippocampal mGluR-LTD and associated behaviors. Moreover, rapamycin blocks mGluR-LTD in mTORC1-deficient mice. However, both rapamycin and mGluR activation regulate mTOR complex 2 (mTORC2) activity, and mTORC2-deficient mice show impaired mGluR-LTD and associated behaviors. Thus, mTORC2 is a major regulator of mGluR-LTD. PMID- 29786080 TI - Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation. AB - The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of beta-sheet rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible beta-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation. PMID- 29786084 TI - Beyond the maternal epigenetic legacy. PMID- 29786083 TI - Attention improves memory by suppressing spiking-neuron activity in the human anterior temporal lobe. AB - We identify a memory-specific attention mechanism in the human anterior temporal lobe, an area implicated in semantic processing and episodic memory formation. Spiking neuron activity is suppressed and becomes more reliable in preparation for verbal memory formation. Intracranial electroencephalography signals implicate this region as a source of executive control for attentional selection. Consistent with this interpretation, its surgical removal causes significant memory impairment for attended words relative to unattended words. PMID- 29786085 TI - Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety. AB - The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release. PMID- 29786087 TI - A comparison of 23-gauge and 20-gauge vitrectomy for proliferative sickle cell retinopathy - clinical outcomes and surgical management. AB - AIMS: To report anatomical and functional outcomes in patients with proliferative sickle retinopathy (PSR) who underwent 23-gauge (23G) and 20-gauge (20G) vitrectomy. METHODS: Retrospective consecutive case series of patients who underwent vitreoretinal intervention for complications of PSR between April 2009 and February 2015. Operations were performed at a tertiary referral centre, Moorfields Eye Hospital. Visual acuity and anatomical success rates were evaluated for PSR complicated by retinal detachment, tractional vitreous haemorrhage and macular hole. Proliferative diabetic retinopathy cases were excluded. RESULTS: A total of 71 eyes (63 patients) underwent vitreoretinal surgery for PSR complications with 26 months mean follow-up. Primary indications were: tractional retinal detachment (TRD, n = 17), TRD with rhegmatogenous retinal detachment (n = 16), rhegmatogenous retinal detachment (n = 5, macula-on: 1, macula-off: 4), vitreous haemorrhage (n = 19), epiretinal membrane (n = 6), and full thickness macula hole (n = 8). Thirty-nine cases underwent 20G vitrectomy, and 23G surgery was performed in 32 eyes. Mean best corrected visual acuity (BCVA) improved from pre-operative 1.30 LogMAR to final BCVA of 0.74 LogMAR (p < 0.01, paired t-test). 23G vitrectomy yielded slightly better 32 vs. 25 ETDRS-letter improvement compared with 20G vitrectomy (p = 0.60, NS, unpaired t-test). 23G was associated with fewer per-operative complications (23G, 18% vs. 20G,13%). The subset of 38 eyes with retinal detachment demonstrated 79% primary reattachment rate, and a smaller BCVA improvement of 3 lines (p = 0.07, paired t test). CONCLUSIONS: Surgical intervention for complicated PSR can preserve and/or improve vision although the degree of visual acuity stabilisation remains guarded in tractional/rhegmatogenous detachments. 23G vitrectomy may give a better functional outcome with lower per-operative complication rates. PMID- 29786086 TI - The effect of autoimmune retinopathy on retinal vessel oxygen saturation. AB - PURPOSE: To study the retinal vessel oxygen saturation alterations in patients with autoimmune retinopathy (AIR) and patients with autoimmune retinopathy associated with retinitis pigmentosa (AIR-RP) in comparison with healthy controls and patients with isolated retinitis pigmentosa (RP). DESIGN: Prospective, cross sectional, and non-interventional study. SUBJECTS: Retinal vessel oximetry (RO) was performed on a total of 139 eyes: six eyes suffering from AIR and four eyes with AIR-RP were compared to 59 healthy control eyes and to 70 eyes with RP. METHODS: A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to evaluate retinal vessel oxygen saturation. The mean oxygen saturation in the first and second branch retinal arterioles (A SO2) and venules (V-SO2) were measured and their difference (A-V SO2) was calculated. In addition, we measured the diameter of the retinal arterioles (D-A) and venules (D-V). MAIN OUTCOME MEASURES: Oxygen metabolism is altered in patients with isolated AIR and AIR-RP. RESULTS: Both, AIR and AIR-RP groups, differed from healthy controls showing significantly higher V-SO2 values and significantly lower A-V SO2 values (p < 0.025). In addition, the AIR-RP group could be differentiated from eyes suffering from isolated RP by means of significantly higher V-SO2 values. Comparing retinal vessel diameters, both, the AIR and AIR-RP groups, presented with significant arterial (p = 0.05) and venular (p < 0.03) vessel attenuation than the healthy control group. CONCLUSIONS: Based on our results, in analogy to patients suffering from RP, oxygen metabolism seems to be altered in AIR patients. PMID- 29786088 TI - Reply to 'Comment on: Carotid-cavernous fistula: current concepts in aetiology, investigation and management'. PMID- 29786089 TI - Spectral analysis of fundus autofluorescence pattern as a tool to detect early stages of degeneration in the retina and retinal pigment epithelium. AB - PURPOSE: The aim of this work is the determination of quantitative diagnostic criteria based on the spectral characteristics of fundus autofluorescence to detect early stages of degeneration in the retina and retinal pigment epithelium (RPE). METHODS: RPE cell suspension samples were obtained from the cadaver eyes with and without signs of age-related macular degeneration (AMD). Fluorescence analysis at an excitation wavelength of 488 nm was performed. The fluorescence lifetimes of lipofuscin-granule fluorophores were measured by counting time correlated photon method. RESULTS: Comparative analysis of fluorescence spectra of RPE cell suspensions from the cadaver eyes with and without signs of AMD showed a significant difference in fluorescence intensity at 530-580 nm in response to fluorescence excitation at 488 nm. It was notably higher in eyes with visual pathology than in normal eyes regardless of the age of the eye donor. Measurements of fluorescence lifetimes of lipofuscin fluorophores showed that the contribution of photooxidation and photodegradation products of bisretinoids to the total fluorescence at 530-580 nm of RPE cell suspensions was greater in eyes with visual pathology than in normal eyes. CONCLUSION: Because photooxidation and photodegradation products of bisretinoids are markers of photodestructive processes, which can cause RPE cell death and initiate degenerative processes in the retina, quantitative determination of increases in these bisretinoid products in lipofuscin granules may be used to establish quantitative diagnostic criteria for degenerative processes in the retina and RPE. PMID- 29786090 TI - CRISPR off-target analysis in genetically engineered rats and mice. AB - Despite widespread use of CRISPR, comprehensive data on the frequency and impact of Cas9-mediated off-targets in modified rodents are limited. Here we present deep-sequencing data from 81 genome-editing projects on mouse and rat genomes at 1,423 predicted off-target sites, 32 of which were confirmed, and show that high fidelity Cas9 versions reduced off-target mutation rates in vivo. Using whole genome sequencing data from ten mouse embryos, treated with a single guide RNA (sgRNA), and from their genetic parents, we found 43 off-targets, 30 of which were predicted by an adapted version of GUIDE-seq. PMID- 29786091 TI - Automated, parallel mass spectrometry imaging and structural identification of lipids. AB - We report a method that enables automated data-dependent acquisition of lipid tandem mass spectrometry data in parallel with a high-resolution mass spectrometry imaging experiment. The method does not increase the total image acquisition time and is combined with automatic structural assignments. This lipidome-per-pixel approach automatically identified and validated 104 unique molecular lipids and their spatial locations from rat cerebellar tissue. PMID- 29786092 TI - Mapping the physical network of cellular interactions. AB - A cell's function is influenced by the environment, or niche, in which it resides. Studies of niches usually require assumptions about the cell types present, which impedes the discovery of new cell types or interactions. Here we describe ProximID, an approach for building a cellular network based on physical cell interaction and single-cell mRNA sequencing, and show that it can be used to discover new preferential cellular interactions without prior knowledge of component cell types. ProximID found specific interactions between megakaryocytes and mature neutrophils and between plasma cells and myeloblasts and/or promyelocytes (precursors of neutrophils) in mouse bone marrow, and it identified a Tac1+ enteroendocrine cell-Lgr5+ stem cell interaction in small intestine crypts. This strategy can be used to discover new niches or preferential interactions in a variety of organs. PMID- 29786093 TI - Author Correction: High-speed volumetric imaging of neuronal activity in freely moving rodents. AB - In the version of this Brief Communication originally published online, ref. 21 included details for a conference paper (Pegard, N. C. et al. Paper presented at Novel Techniques in Microscopy: Optics in the Life Sciences, Vancouver, BC, Canada, 12-15 April 2015). The correct reference is the following: Pegard, N. C. et al. Optica 3, 517-524 (2016). This error has been corrected in the print, HTML and PDF versions of the paper. PMID- 29786094 TI - A protein activity assay to measure global transcription factor activity reveals determinants of chromatin accessibility. AB - No existing method to characterize transcription factor (TF) binding to DNA allows genome-wide measurement of all TF-binding activity in cells. Here we present a massively parallel protein activity assay, active TF identification (ATI), that measures the DNA-binding activity of all TFs in cell or tissue extracts. ATI is based on electrophoretic separation of protein-bound DNA sequences from a highly complex DNA library and subsequent mass-spectrometric identification of the DNA-bound proteins. We applied ATI to four mouse tissues and mouse embryonic stem cells and found that, in a given tissue or cell type, a small set of TFs, which bound to only ~10 distinct motifs, displayed strong DNA binding activity. Some of these TFs were found in all cell types, whereas others were specific TFs known to determine cell fate in the analyzed tissue or cell type. We also show that a small number of TFs determined the accessible chromatin landscape of a cell, suggesting that gene regulatory logic may be simpler than previously appreciated. PMID- 29786097 TI - Spot urine and 24-h diet recall estimates of dietary sodium intake from the 2008/09 New Zealand Adult Nutrition Survey: a comparison. AB - BACKGROUND: We aimed to test the difference between estimates of dietary sodium intake using 24-h diet recall and spot urine collection in a large sample of New Zealand adults. METHODS: We analysed spot urine results, 24-h diet recall, dietary habits questionnaire and anthropometry from a representative sample of 3312 adults aged 15 years and older who participated in the 2008/09 New Zealand Adult Nutrition Survey. Estimates of adult population sodium intake were derived from 24-h diet recall and spot urine sodium using a formula derived from analysis of INTERSALT data. Correlations, limits of agreement and mean difference were calculated for the total sample, and for population subgroups. RESULTS: Estimated total population 24-h urinary sodium excretion (mean (95% CI)) from spot urine samples was 3035 mg (2990, 3079); 3612 mg (3549, 3674) for men and 2507 mg (2466, 2548) for women. Estimated mean usual daily sodium intake from 24-h diet recall data (excluding salt added at the table) was 2564 mg (2519, 2608); 2849 mg (2779, 2920) for men and 2304 mg (2258, 2350) for women. Correlations between estimates were poor, especially for men, and limits of agreement using Bland-Altman mean difference analysis were wide. CONCLUSIONS: There is a poor agreement between estimates of individual sodium intake from spot urine collection and those from 24-hour diet recall. Although, both 24-hour dietary recall and estimated urinary excretion based on spot urine indicate mean population sodium intake is greater than 2 g, significant differences in mean intake by method deserve further investigation in relation to the gold standard, 24-hour urinary sodium excretion. PMID- 29786096 TI - Reversal of siRNA-mediated gene silencing in vivo. AB - We report rapid, potent reversal of GalNAc-siRNA-mediated RNA interference (RNAi) activity in vivo with short, synthetic, high-affinity oligonucleotides complementary to the siRNA guide strand. We found that 9-mers with five locked nucleic acids (LNAs) have the highest potency across several targets. Our modular, sequence-specific approach, named REVERSIR, may enhance the therapeutic profile of any long-acting GalNAc-siRNA (short interfering RNA) conjugate by enabling control of RNAi pharmacology. PMID- 29786095 TI - High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR-Cas9 in yeast. AB - Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80 100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion mutants that span the length of the protein and a series of point mutations against highly conserved residues in the protein. In addition, we created a genome-wide library targeting 315 poorly characterized small open reading frames (smORFs, <100 amino acids in length) scattered throughout the yeast genome, and assessed which are vital for growth under various environmental conditions. Our strategy allows fundamental biological questions to be investigated in a high-throughput manner with precision. PMID- 29786098 TI - Syntheses, structures, and magnetic properties of three new MnII-[MoIII(CN)7]4- molecular magnets. AB - By reaction of K4[MoIII(CN)7].2H2O, Mn(ClO4)2.6H2O and bidentate chelating ligands, three new cyano-bridged compounds, namely Mn2(3 pypz)(H2O)(CH3CN)[Mo(CN)7] (1), Mn2(1-pypz)(H2O)(CH3CN)[Mo(CN)7] (2) and Mn2(pyim)(H2O)(CH3CN)[Mo(CN)7] (3) (3-pypz = 2-(1H-pyrazol-3-yl)pyridine, 1-pypz = 2-(1H-pyrazol-1-yl)pyridine, pyim = 2-(1H-imidazol-2-yl)pyridine), have been synthesized and characterized structurally and magnetically. Single crystal X-ray analyses revealed that although the chelating ligands are different, compounds 1 to 3 are isomorphous and crystallize in the same monoclinic space group C2/m. Connected by the bridging cyano groups, one crystallographically unique [Mo(CN)7]4- unit and three crystallographically unique MnII ions of different coordination environments form similar three-dimensional frameworks, which have a four-nodal 3,4,4,7-connecting topological net with a vertex symbol of {43}{44.62}2{410.611}. Magnetic measurements revealed that compounds 1-3 display long-range magnetic ordering with critical temperatures of 64, 66 and 62 K, respectively. These compounds are rare examples of a small number of chelating co ligand coordinated [Mo(CN)7]4--based magnetic materials. Specifically, the bidentate chelating ligands were successfully introduced into the heptacyanomolybdate system for the first time. PMID- 29786099 TI - Cluster-to-cluster transformation among Au6, Au8 and Au11 nanoclusters. AB - We present the cluster-to-cluster transformations among three gold nanoclusters, [Au6(dppp)4]2+ (Au6), [Au8(dppp)4Cl2]2+ (Au8) and [Au11(dppp)5]3+ (Au11). The conversion process follows a rule that states that the transformation of a small cluster to a large cluster is achieved through an oxidation process with an oxidizing agent (H2O2) or with heating, while the conversion of a large cluster to a small one occurs through a reduction process with a reducing agent (NaBH4). All the reactions were monitored using UV-Vis spectroscopy and ESI-MS. This work may provide an alternative approach to the synthesis of novel gold nanoclusters and a further understanding of the structural transformation relationship of gold nanoclusters. PMID- 29786100 TI - A multifunctional Eu-CP as a recyclable luminescent probe for the highly sensitive detection of Fe3+/Fe2+, Cr2O72-, and nitroaromatic explosives. AB - A novel 2D lanthanide coordination polymer {Eu-CP (1)} based on a 3-bis(3 carboxyphenyl)imidazolium (L) ligand was successfully assembled through a solvothermal method. Luminescence tests indicate that 1 has excellent selectivity and sensitivity to detect Fe3+/Fe2+, Cr2O72-, and a series of nitroaromatic explosives. Interestingly, 1 can effectively distinguish CrVI anions (CrO42 /Cr2O72-), which is difficult for most of the reported CPs. Furthermore, in the detection process, 1 can be simply and quickly regenerated and reused at least five times. As far as we know, 1 is the first multifunctional Eu-CP used as a luminescent probe to detect Fe3+/Fe2+, Cr2O72-, and a series of nitroaromatic explosives (NAEs) based on the imidazolium derivative. PMID- 29786101 TI - A PEG/copper(i) halide cluster as an eco-friendly catalytic system for C-N bond formation. AB - The catalytic activities of eight copper(i) halide clusters assembled from copper(i) halide and ferrocenyltelluroethers, 1-8, were investigated in C-N formation under various conditions. A catalytic procedure using poly(ethylene glycol) (PEG-400) as a greener alternative organic solvent has been developed. The PEG-400/5 system can achieve 99% targeted yield with a mild reaction temperature and short reaction time. After the isolation of the products by extraction with diethyl ether, this PEG-400/cluster system could be easily recycled. Spectroscopic studies elucidate a stepwise mechanism: firstly, proton coupled electron transfer (PCET) involving the transfer of an electron from Cu+ and a proton from imidazole results in the formation of a labile penta coordinated Cu2+ and aryl radical; the following effective electron transfer from the ferrocene unit reduces Cu2+ and forms the target product; finally, the ferrocenium unit is reduced by the I- anion. The merits of this eco-friendly synthesis are the efficient utilization of reagents and easy recyclability. PMID- 29786103 TI - True polyploid meiosis in the human male. AB - Polyploidy does not usually occur in germinal cells of mammals and other higher vertebrates. We describe a unique example of mosaic autotetraploidy in the meiosis of a human male. Although the original observations were made in the late 1960s, we did not publish them at that time, because we expected to detect further examples that could be described together. However, this did not occur and we have now decided to make the observations available to demonstrate that polyploidy in mammalian male meiosis can arise at a higher frequency than expected by random polyploidization of individual meiotic cells, by either DNA duplication or cell fusion prior to synapsis. This is the first description of a population of primary spermatocytes exhibiting multivalent formation at leptotene /diakinesis in human spermatogenesis, with ring, chain, frying pan and other types of quadrivalents, typical of autotetraploidy. As many of the polyploid configurations showed apoptotic breakdown, it is likely that diploid and/or aneuploid spermatozoa would have rarely or never resulted from this mosaic autotetraploid meiosis. PMID- 29786102 TI - The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population. AB - We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors. PMID- 29786104 TI - Correlation between the expression of IL-18 and deep venous thrombosis. AB - The present study aimed to investigate the effect of the expression of interleukin (IL)-18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague-Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL 18, nuclear factor (NF)-kappaB and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL-18 overexpression and inhibition vectors were constructed. The expression levels of IL-18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL-18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL-18, NF-kappaB and vWF were high in the blood samples with the occurrence and development of thrombosis (P<0.05). The weight, length and weight/length ratio of thrombi in each model group showed significant differences from those in the control group (P<0.05) with the overexpression of IL-18, and the expression levels of NF-kappaB and vWF in venous tissues were altered with abnormal expression levels of IL-18. IL-18 damaged HUVECs and significantly increased viability in early-stage apoptosis, promoted the upregulation of vWF and P-selectin, and reduced tissue plasminogen activator. IL-18 and the related markers were closely associated with the occurrence and development of DVT. PMID- 29786105 TI - Cannabinoid WIN-55,212-2 mesylate inhibits tumor necrosis factor-alpha-induced expression of nitric oxide synthase in dorsal root ganglion neurons. AB - Tumor necrosis factor-alpha (TNF-alpha) is an established pain modulator in the peripheral nervous system. Elevated levels of TNF-alpha in dorsal root ganglion (DRG) neurons reportedly is critical for neuropathic pain processing. It has been shown that the production of nitric oxide, a key player in the development and maintenance of nociception, depends on the expression of nitric oxide synthases (NOSs) and their activities. Accumulating evidence also supports an important role of cannabinoids in modulating neuropathic pain. In this study, we explored the effects and the underlying mechanisms of crosstalk between TNF-alpha and cannabinoid on the expression/activity of NOS in DRG neurons. With or without knockdown of p38 mitogen-activated protein kinase (MAPK), DRG neurons were treated with TNF-alpha in the presence or absence of synthetic cannabinoid WIN 55,212-2 mesylate (WIN-55) and selective cannabinoid receptor (CB) antagonists. TNF-alpha significantly increased the NOS activity as well as the mRNA stability and expression of neuronal NOS (nNOS) in DRG neurons; this was abolished by inhibiting p38 MAPK signaling. WIN-55 inhibited TNF-alpha-induced p38 MAPK activity as well as TNF-alpha-induced increase of mRNA stability and expression/activity of nNOS; the inhibitory effect of WIN-55 was blocked by a selective CB2 antagonist. Our findings suggest that TNF-alpha induces the expression/activity of nNOS in DRG neurons by increasing its mRNA stability by a p38 MAPK-dependent mechanism; WIN-55 inhibits this effect of TNF-alpha by inhibiting p38 MAPK via CB2. By linking the functions of TNF-alpha, NOS and cannabinoid in DRG neurons, this study adds new insights into the molecular mechanisms underlying the pharmacologic effects of cannabinoids on neuropathic pain as well as into the pathophysiology of neuropathic pain. PMID- 29786106 TI - Efficient delivery of HBV NLS siRNAs into HepG2.2.15 cells for HBV inhibition through novel recombinant preS1-tP proteins. AB - Hepatitis B virus (HBV) infection and related liver complications remain severe public health problems worldwide. Previous investigations have shown that small interfering (si)RNAs can offer an effective strategy for the treatment of chronic hepatitis B. The present study aimed to develop a novel siRNA-delivering system of therapeutic HBV nuclear localization sequence (NLS) siRNAs using the recombinant preS1-truncated protamine (tP) proteins. The preS1 region of the LHB was used in place of scFv to construct the recombinant preS1-tP proteins, which were applied to deliver siRNAs targeting the HBV NLS to inhibit HBV replication and infection in HepG2.2.15 cells overexpressing sodium taurocholate cotransporting polypeptide (NTCP). The results revealed that HepG2.2.15 cells with stable NTCP expression (HepG2.2.15-NTCP cells) transfected with the recombinant lentivirus showed increased expression of NTCP genes. The HBV NLS siRNAs significantly suppressed HBV mRNA content and levels of HBsAg and HBeAg in the HepG2.2.15-NTCP cells. Recombinant preS1-tP proteins tagged with His and glutathione S-transferase were found to enter into HepG2.2.15-NTCP cells and bind with DNA. The HBV NLS siRNAs were delivered into HepG2.2.15-NTCP cells by recombinant preS1-tP proteins, which resulted in decreased expression of HBV mRNA, HBsAg and HBeAg, HBV DNA and covalently closed circular DNA in the HepG2.2.15-NTCP cells. Therefore, the recombinant preS1-tP proteins successfully delivered NLS siRNAs into HepG2.2.15 cells and repressed HBV infection and replication. PMID- 29786107 TI - E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non-small-cell lung cancer cells. AB - Hakai was originally identified as an E3 ubiquitin ligase of the E-cadherin complex implicated in cell adhesion and invasion. Recently, emerging evidence has strongly suggested that Hakai serves a pivotal role in the tumorigenesis of certain tumors. However, the role of Hakai in non-small-cell lung cancer (NSCLC) and its underlying molecular mechanism have not been clarified. In the present study, it was observed that Hakai was highly expressed in NSCLC cell lines compared with human normal bronchial epithelial cells, and transfection with Hakai small interfering RNA significantly inhibited the growth of A549 and NCI H460 NSCLC cells. In addition, the inhibition of Hakai suppressed NSCLC cell migration and invasion through upregulation of E-cadherin and downregulation of N cadherin. Notably, it was also revealed that knockdown of Hakai led to a decrease in the expression of phosphorylated AKT (Ser473), and a significant enhancement of chemosensitivity to cisplatin was observed following Hakai suppression. In conclusion, the present study demonstrated for the first time that knockdown of Hakai inhibited the proliferation, migration and invasion of NSCLC cells, and sensitized NSCLC cells to cisplatin. Thus, Hakai may serve as a potential therapeutic target for the treatment of NSCLC. PMID- 29786108 TI - miR-494 inhibits cancer-initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2-positive gastric cancer. AB - In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP-competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2-positive gastric cancer. The aim of the present study was to explore the effects of miR-494 and FGFR2 in regulation of cancer initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2 positive gastric cancer. Western blot analysis was used to identify that the expression of fibroblast growth factor receptor 2 (FGFR2), a receptor tyrosine kinase, was upregulated in gastric cancer tissues. Formation of cancer initiating cells (CICs) and resistance to lapatinib were determined using sphere growth assay and MTT assay, respectively. The overexpression of FGFR2 promoted the generation of cancer-initiating cells (CICs) and resistance to lapatinib in HER2 positive gastric cancer YCC1 cells. In addition, it was observed that overexpression of microRNA (miR)-494 downregulated the protein expression of FGFR2, inhibited the formation of CICs and reversed lapatinib resistance in YCC1 F cells (HER2-positive, FGFR2 overexpressing and lapatinib-resistant gastric cancer cells). Therefore, it was concluded that miR-494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2 positive gastric cancer. PMID- 29786109 TI - Engulfment of platelets delays endothelial cell aging via girdin and its phosphorylation. AB - Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood-brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co-cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co-localization of PLTs, girders of actin filament (girdin) and phosphorylated (p-)girdin. Senescence-associated beta galactosidase (beta-gal) staining, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and flow cytometry were performed to examine the cell senescence, viability and apoptosis, respectively. Transwell assays were performed to examine cell invasion and migration. Western blot analysis was performed to detect the expression of girdin, AKT and p-AKT. PLTs delayed senescence, and promoted the viability and resistance to apoptosis of the HBMECs. Cell invasion and migration were enhanced by PLTs. In addition, girdin and p girdin were essential to the engulfment of HBMECs to PLTs. Mechanically, the inhibition of AKT signals reversed the effect of PLTs on HBMECs by increasing the activity of beta-gal, decreasing the cell viability, and inhibiting the invasion and migration of the HBMECs. The engulfment of PLTs assisted in delaying the aging of endothelial cells via girdin and p-girdin, in which the AKT signal was involved. The present study indicated a potential strategy for delaying endothelial cell aging in the treatment of central nervous system diseases. PMID- 29786111 TI - High glucose suppresses the viability and proliferation of HTR-8/SVneo cells through regulation of the miR-137/PRKAA1/IL-6 axis. AB - The aim of the present study was to investigate the mechanism underlying the high glucose (HG)-associated regulation of HTR-8/SVneo cell viability and proliferation during gestational diabetes mellitus (GDM), and to verify the association of microRNA (miR)-137, protein kinase AMP-activated catalytic subunit alpha1 (PRKAA1) and interlukin-6 (IL-6). miR-137-overexpressing and negative control HTR-8/SVneo cells were established by lentiviral vector infection. Cell Counting Kit-8 and colony formation assays were used to analyze the viability and proliferation of HTR-8/SVneo cells. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the transcriptional activity of miR 137, PRKAA1 and Il-6, and ELISA and western blot analysis were used to measure the protein levels of IL-6 and PRKAA1, respectively. It was demonstrated that PRKAA1 was decreased in the placental tissues of women with GDM and HG-treated HTR-8/SVneo cells, and that HG upregulated miR-137 and IL-6 in trophoblasts. The overexpression of miR-137 decreased levels of PRKAA1 and increased levels of IL-6 in the HTR-8/SVneo cells. An inhibitor of PRKAA1 promoted the secretion of IL-6, whereas an agonist of PRKAA1 suppressed the production of IL-6. HG treatment and the overexpression of miR-137 reduced the viability and proliferation of HTR 8/SVneo cells in vitro, whereas the activation of PRKAA1 or incubation with IL-6 antibody reversed these effects. Overall, it was concluded that HG suppressed the viability and proliferation of trophoblast cells through the miR-137/PRKAA1/IL-6 axis, which may contribute to pathological changes of placental tissues in GDM. PMID- 29786110 TI - Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/beta-catenin signaling activation (Review). AB - beta-catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E-cadherin/CDH1, N-cadherin/CDH2, VE-cadherin/CDH5 and alpha catenins), transmembrane-type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain-of-function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss-of-function CTNNB1 mutations are also detected in human cancer. ABCB1, ALDH1A1, ASCL2, ATF3, AXIN2, BAMBI, CCND1, CD44, CLDN1, CTLA4, DKK1, EDN1, EOMES, FGF18, FGF20, FZD7, IL10, JAG1, LEF1, LGR5, MITF, MSX1, MYC, NEUROD1, NKD1, NODAL, NOTCH2, NOTUM, NRCAM, OPN, PAX3, PPARD, PTGS2, RNF43, SNAI1, SP5, TCF7, TERT, TNFRSF19, VEGFA and ZNRF3 are representative beta-catenin target genes. beta-catenin signaling is involved in myofibroblast activation and subsequent pulmonary fibrosis, in addition to other types of fibrosis. beta-catenin and NF-kappaB signaling activation are involved in field cancerization in the stomach associated with Helicobacter pylori (H. pylori) infection and in the liver associated with hepatitis C virus (HCV) infection and other etiologies. beta-catenin-targeted therapeutics are functionally classified into beta-catenin inhibitors targeting upstream regulators (AZ1366, ETC-159, G007-LK, GNF6231, ipafricept, NVP-TNKS656, rosmantuzumab, vantictumab, WNT-C59, WNT974 and XAV939), beta-catenin inhibitors targeting protein-protein interactions (CGP049090, CWP232228, E7386, ICG-001, LF3 and PRI-724), beta-catenin inhibitors targeting epigenetic regulators (PKF118 310), beta-catenin inhibitors targeting mediator complexes (CCT251545 and cortistatin A) and beta-catenin inhibitors targeting transmembrane-type transcriptional outputs, including CD44v6, FZD7 and LGR5. Eradicating H. pylori and HCV is the optimal approach for the first-line prevention of gastric cancer and hepatocellular carcinoma (HCC), respectively. However, beta-catenin inhibitors may be applicable for the prevention of organ fibrosis, second-line HCC prevention and treating beta-catenin-driven cancer. The multi-layered prevention and treatment strategy of beta-catenin-related human diseases is necessary for the practice of personalized medicine and implementation of precision medicine. PMID- 29786112 TI - CTLA-4 interferes with the HBV-specific T cell immune response (Review). AB - Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of T cells, resulting in weak or absent virus specific T cells reactivity, which is described as 'exhaustion'. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells. Persistent HBV infection results in the upregulation of CTLA-4 on hepatic CD8+ T cells. This prompts CD8+ T cell apoptosis, and the activation of cytotoxic T lymphocytes is blocked. Similar to CD8+ T cells, CD4+ T helper (Th) cell proliferation is hindered following CTLA-4 upregulation. In addition, the differentiation of CD4+ Th is polarized toward the Th2/peripherally-inducible T regulatory cell types, increasing the levels of anti-inflammatory cytokines. Conversely, the activation of proinflammatory cells (Th1 and follicular helper T) is blocked, and the levels of proinflammatory cytokines decline. This review summarizes the current literature relevant to T cell exhaustion in patients with HBV-related chronic hepatitis, and discusses the roles of CTLA-4 in T cell exhaustion. PMID- 29786113 TI - Overexpression of C-sis inhibits H2O2-induced Buffalo rat liver cell apoptosis in vitro and alleviates liver injury in a rat model of fulminant hepatic failure. AB - The present study aimed to investigate the role of the C-sis gene in the apoptosis of hepatocytes in vitro and in the liver function of a rat model of fulminant hepatic failure (FHF). Buffalo rat liver (BRL) cells were treated with hydrogen peroxide (H2O2) to induce apoptosis and then transfected with a C-sis overexpression vector. A rat model of FHF was established, and C-sis was overexpressed. The mRNA and protein expression of C-sis were examined using reverse transcription-polymerase chain reaction and western blot analyses, respectively. Cell viability was assessed by CCK8, and a TUNEL assay was used to examine cell apoptosis. Flow cytometry was used for cell cycle detection. Hematoxylin and eosin staining was used for histological examination. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also examined in the rats. The results showed that C-sis was successfully overexpressed in the cells and rat model. Compared with H2O2-treated BRL cells, the overexpression of C-sis significantly inhibited cell apoptosis, promoted cell viability, and decreased the expression of cleaved caspase-3. Similar results were observed in the FHF rats treated with the C-sis overexpression plasmid, compared with those treated with empty plasmids. In addition, in the FHF rats overexpressing C-sis, histological examination showed that liver injury was alleviated, the levels of ALT and AST were significantly decreased, and mortality rate was significantly decreased, compared with those observed in the rats treated with empty plasmids. In conclusion, the overexpression of C-sis inhibited the H2O2-induced apoptosis of BRL cells in vitro, and alleviated liver injury, improved liver function, and decreased mortality rates in rat models of FHF. PMID- 29786114 TI - Endothelium-dependent vasodilation in the cerebral arterioles of rats deteriorates during acute hyperglycemia and then is restored by reducing the glucose level. AB - PURPOSE: Acute hyperglycemia in patients with traumatic brain injury correlates with a poor neurological outcome. We investigated the endothelium function of rat cerebral arterioles during acute hyperglycemia and after reducing the glucose levels using insulin. We also examined whether or not oxidative stress was involved in the cerebral arteriole response to acute hyperglycemia. METHODS: In isoflurane-anesthetized, mechanically ventilated rats, we used closed cranial window preparation to measure the changes in the pial arteriolar diameter following the topical application of acetylcholine (ACh) or adenosine. We examined the pial arteriolar vasodilator response before hyperglycemia, during hyperglycemia, and after reducing the glucose level using insulin. After intravenous pretreatment with an NADPH oxidase inhibitor (apocynin or diphenylene iodonium), we reexamined the pial arteriolar vasodilator response following the topical application of ACh. RESULTS: Under control conditions, the topical application of ACh dose-dependently dilated the cerebral arterioles. The vasodilatory responses to topical ACh were impaired during hyperglycemia and improved after the administration of insulin. The vasodilatory responses to topical adenosine were not affected by the glucose levels. In the apocynin or diphenylene iodonium pretreatment group, the topical application of ACh dilated the cerebral arterioles during hyperglycemia. CONCLUSION: Acute hyperglycemia induces a dysfunction of the endothelium-dependent vasodilation of rat cerebral arterioles. The dysfunction can be reversed by improving the acute hyperglycemia and it can be prevented entirely by the administration of NADPH oxidase inhibitors. These results could suggest that controlling the glucose levels works protectivity to endothelium function of cerebral arterioles. PMID- 29786115 TI - Effects of cardiac output on the onset of rocuronium-induced neuromuscular block in elderly patients. AB - PURPOSE: The aim of this study was to elucidate the relationship between the onset of rocuronium-induced neuromuscular block and arterial pressure-based cardiac output (CO) in elderly patients. METHODS: Forty elderly patients aged 65 83 years were enrolled in this study. After induction of anesthesia, contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation were acceleromyographically evaluated and 1 mg/kg rocuronium was administered following CO measurement. The correlation between onset of rocuronium action and CO was analyzed. RESULTS: The mean [SD] CO reduced after induction of anesthesia from 5.1 [1.8] L/min to 3.8 [1.1] L/min. The onset time of rocuronium-induced neuromuscular block was 110.3 [23.9] s (range 60-165). There was a statistically significant inverse correlation between the onset time of rocuronium and CO [onset time (s) = - 13.2.CO + 159.7, R2 = 0.376]. CONCLUSIONS: In the elderly, CO influences the onset of action of rocuronium. PMID- 29786116 TI - Is childbirth-induced PTSD associated with low maternal attachment? AB - Few studies examined maternal attachment in childbirth-related postpartum posttraumatic stress disorder (PP-PTSD). We studied 685 postpartum women, assessing for PP-PTSD, non-childbirth PTSD, maternal attachment, pre-birth, birth, and post-birth factors. Attachment was lower in PP-PTSD than in non childbirth PTSD and no PP-PTSD. Hierarchical regression showed that PP-PTSD predicted less maternal attachment above and beyond pre-birth psychiatric conditions, acute distress in birth, and lack of breastfeeding. Childbirth induced posttraumatic stress may interfere with the formation of maternal attachment, warranting screening of at-risk women. PMID- 29786117 TI - The relevance of the Hippocratic Oath to the ethical and moral values of contemporary medicine. Part II: interpretation of the Hippocratic Oath-today's perspective. AB - This is the second part of a paper on the relevance and significance of the Hippocratic Oath to modern medical ethical and moral values with the aim at answering questions on controversial issues related to the Oath. Part I argued that the general attributes and ethical values of the Oath are relevant to the modern world. Part II attempts to elucidate the interpretation of the specific injunctions of the Oath from today's perspective in relation to ethical values concerning the duties of physicians to patients and society. The objective is to prove that the Oath has established the general context of medical ethics of the physician-patient relationship, which reflects long-lasting moral values that still define the medical profession. The Oath has exemplified the fundamental modern ethical principles of beneficence, non-maleficence and confidentiality. Its foremost message focuses on patients' best interests and not on the prohibition of surgery, euthanasia or abortion, as is generally believed. Furthermore, the Oath as a code of professional identity has had a powerful impact on modem judicial opinions regarding medical ethics. In a lot of ways, it is as relevant of the values of contemporary medicine as it was for ancient medicine. These slides can be retrieved under Electronic Supplementary Material. PMID- 29786118 TI - An optimized fed-batch culture strategy integrated with a one-step fermentation improves L-lactic acid production by Rhizopus oryzae. AB - In previous work, we proposed a novel modified one-step fermentation fed-batch strategy to efficiently generate L-lactic acid (L-LA) using Rhizopus oryzae. In this study, to further enhance efficiency of L-LA production through one-step fermentation in fed-batch cultures, we systematically investigated the initial peptone- and glucose-feeding approaches, including different initial peptone and glucose concentrations and maintained residual glucose levels. Based on the results of this study, culturing R. oryzae with initial peptone and glucose concentrations of 3.0 and 50.0 g/l, respectively, using a fed-batch strategy is an effective approach of producing L-LA through one-step fermentation. Changing the residual glucose had no obvious effect on the generation of L-LA. We determined the maximum LA production and productivity to be 162 g/l and 6.23 g/(l.h), respectively, during the acid production stage. Compared to our previous work, there was almost no change in L-LA production or yield; however, the productivity of L-LA increased by 14.3%. PMID- 29786119 TI - Full-length and defective enterovirus G genomes with distinct torovirus protease insertions are highly prevalent on a Chinese pig farm. AB - Recombination occurs frequently between enteroviruses (EVs) which are classified within the same species of the Picornaviridae family. Here, using viral metagenomics, the genomes of two recombinant EV-Gs (strains EVG 01/NC_CHI/2014 and EVG 02/NC_CHI/2014) found in the feces of pigs from a swine farm in China are described. The two strains are characterized by distinct insertion of a papain like protease gene from toroviruses classified within the Coronaviridae family. According to recent reports the site of the torovirus protease insertion was located at the 2C/3A junction region in EVG 02/NC_CHI/2014. For the other variant EVG 01/NC_CHI/2014, the inserted protease sequence replaced the entire viral capsid protein region up to the VP1/2A junction. These two EV-G strains were highly prevalent in the same pig farm with all animals shedding the full-length genome (EVG 02/NC_CHI/2014) while 65% also shed the capsid deletion mutant (EVG 01/NC_CHI/2014). A helper-defective virus relationship between the two co circulating EV-G recombinants is hypothesized. PMID- 29786120 TI - Identification and characterization of a tombusvirus isolated from Japanese gentian. AB - The DECS (dsRNA isolation, exhaustive amplification, cloning and sequencing) analysis technique for viral diagnosis detected a tombusvirus in Japanese gentian not displaying severe symptoms. We tentatively named this virus "gentian virus A" (GeVA). GeVA systemically but inefficiently infected Japanese gentian without causing visible symptoms, while it led to severe symptoms in some other plants. The complete genome sequence of GeVA indicated a typical tombusvirus-like structure. Phylogenetic analysis of the deduced amino acid sequences of four tombusvirus-encoded proteins did not reveal other known tombusviruses that were closely-related to GeVA, suggesting that it is a novel tombusvirus. PMID- 29786121 TI - Genome sequence of the novel virulent bacteriophage PMBT14 with lytic activity against Pseudomonas fluorescens DSM 50090R. AB - Psychrotrophic gram-negative Pseudomonas spp. represent a serious problem in the dairy industry as they can cause spoilage of milk and dairy products. Bacteriophages have moved into focus as promising biocontrol agents for such food spoilage bacteria. The virulent Siphoviridae phage PMBT14 was isolated on a mutant variant of P. fluorescens DSM 50090 challenged with an unrelated virulent P. fluorescens DSM 50090 Podoviridae phage (i.e., mutant strain DSM 50090R). PMBT14 has a 47,820-bp dsDNA genome with 76 predicted open reading frames (ORFs). Its genome shows no significant sequence similarity to that of known phages, suggesting that PMBT14 represents a novel phage. Phage PMBT14 could be a promising biocontrol agent for P. fluorescens in milk or dairy foods. PMID- 29786122 TI - Complete genomic sequence of a novel macluravirus, alpinia oxyphylla mosaic virus (AloMV), identified in Alpinia oxyphylla. AB - A macluravirus, tentatively named alpinia oxyphylla mosaic virus (AloMV), was identified in Alpinia oxyphylla, and its complete genomic sequence determined. The positively single-stranded RNA genome is comprised of 8213 nucleotides excluding the poly (A) tail, and contains one large open reading frame encoding a polyprotein of 2,626 amino acids. Blastp search showed that the polyprotein of AloMV shared 48%~68% aa sequence identities with other reported macluraviruses. Phylogenetic analysis based on the nucleotide sequence of the polyprotein showed that AloMV, together with all other macluraviruses, clustered into the same group most closely related to cardamom mosaic virus, sharing 66.3% nt and 68% aa sequence identities, respectively. These data above suggest that AloMV represents an isolate of a putative new member within the genus Macluravirus. PMID- 29786123 TI - Genetic variations in LTA gene and PDCD1 gene and intrauterine infection of hepatitis B virus: a case-control study in China. AB - Intrauterine infection with hepatitis B virus (HBV) has been suggested to accounting for most cases of chronic HBV infection, which cannot be blocked by combined immunoprophylaxis. The fact that the genetic background might impact the susceptibility to intrauterine infection of HBV has been identified by recent researches. A case-control study included sixty-nine HBsAg-positive mother newborn pairs with intrauterine infection as cases compared to 138 mother-newborn pairs without intrauterine infection as controls. We studied the correlations between HBV intrauterine transmission and 15 maternal SNPs in eight genes (LTA, LTBR, TNFSF14, PDCD1, APOBEC3B, CD274, CD40 and CD40LG). There was a substantially significantly decreased risk of intrauterine infection of HBV in mothers with the rs2227981 TT genotype in PDCD1 gene compared to those with the rs2227981 GG genotype (OR 0.11, 95% CI 0.01-0.95, P = 0.045). Under recessive model (OR 0.51, 95% CI 0.26-1, P = 0.050) and additive model (OR 0.50, 95% CI 0.28-0.88, P = 0.017), we also found a marginally significantly decreased risk of intrauterine infection of HBV. Furthermore, under additive model, maternal genotype for rs2239704 in LTA gene was marginally significantly related to an increased risk of intrauterine HBV infection (OR 1.62, 95% CI 1-6.66, P = 0.055). However, there were no statistically significant associations among the remaining 13 SNPs and the risk of intrauterine infection of HBV. The examination implied that hereditary variants of PDCD1 and LTA genes were associated with intrauterine infection of HBV. PMID- 29786124 TI - Evaluation of the Relationship Between Flap Tension and Tissue Perfusion in Implant-Based Breast Reconstruction Using Laser-Assisted Indocyanine Green Angiography. AB - BACKGROUND: For implant-based breast reconstruction, inadequate tissue perfusion may cause devastating complications. Tissue tension by inadequate implant volume may reduce tissue perfusion by stretching and collapsing the capillaries. The SPY system is used to perform intraoperative fluorescence angiography with indocyanine green to assess visually the blood flow and evaluate tissue perfusion. However, there is no report yet about how mastectomy flap perfusion changes with the expander-filling volume. Therefore, to analyse the changes of tissue perfusion of the mastectomy flap according to the tension level, we used the SPY system and adjusted the filling volume of the tissue expander to change the tension on the skin flap. METHODS: Ten breasts of ten patients who underwent immediate two-stage, implant-based breast reconstructions were included. The expander-filling volume just before mastectomy flap blanching was set as 100%. Based on this, the expander-filling volume was reduced to 50% and increased to 150%. Ingress and egress rates were evaluated using the SPY system at each condition and analysed by a linear mixed model using least square means. RESULTS: The mean ingression rates were 138, 100, and 65%, and the mean egression rates were 145, 100, and 66% at 50, 100, and 150% inflation, respectively. CONCLUSIONS: It was objectively proven that tissue perfusion deteriorates as the tension applied on the flap increases. On the basis of this finding, we can control the amount of inflation volume of the expander or remove the skin in the pre ischaemic condition to reduce complications of implant-based breast reconstruction. PMID- 29786125 TI - Neoadjuvant Chemotherapy Use in Breast Cancer is Greatest in Excellent Responders: Triple-Negative and HER2+ Subtypes. AB - BACKGROUND: While breast cancer has historically been treated with surgery followed by adjuvant chemotherapy (AC) and radiation when indicated, neoadjuvant chemotherapy (NAC) use is thought to be increasing; however, the trends of its use in various biological subtypes have not been evaluated. We sought to evaluate the trend of NAC use over time by biological subtype. METHODS: We identified all patients with invasive breast cancer who underwent curative intent surgery and were treated with chemotherapy from 2010 to 2015 from the National Cancer Database. An unadjusted analysis of trends in proportions over time was performed using Cochran-Armitage trend tests stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. RESULTS: Of 315,264 patients who received chemotherapy, 251,726 (79.8%) received AC and 63,538 (20.2%) received NAC. From 2010 to 2015, significant increases in NAC use were seen in all biologic subtypes (all p < 0.001). The highest proportions and greatest increases in proportions of NAC were seen among triple-negative breast cancers (TNBC; 19.5-33.7%) and HER2+ (HR-/HER2+, 21.5-39.8%; HR+/HER2+, 17.0-33.7%) tumors. HR+/HER2- tumors also had a statistically significant increase in use but this increase was less dramatic (13.0-16.8%) and NAC use in recent years was significantly lower than in other subtypes (p < 0.001). CONCLUSION: Within patients receiving chemotherapy for breast cancer, its receipt in the neoadjuvant setting has been increasing among all biologic subtypes. The highest use of NAC is in TNBC and HER2+ disease, with use in these subgroups being twice as frequent as in HR+/HER2- disease. PMID- 29786126 TI - Prophylactic Central Compartment Neck Dissection in Papillary Thyroid Cancer and Effect on Locoregional Recurrence. AB - BACKGROUND: Prophylactic central compartment neck dissection (pCCND) in addition to total thyroidectomy (TT) includes removal of central compartment lymph nodes in the absence of clinical involvement on preoperative and intraoperative evaluation. The data regarding the influence of pCCND on oncologic outcomes and surgical complication rates is mixed and, therefore, is the focus of this analysis. METHODS: A systematic review of the literature on total thyroidectomy with prophylactic central compartment neck dissection (TT + pCCND) from January 1990 to October 2017 identified 221 abstracts of which 17 met inclusion criteria and were reviewed (1 randomized-control trial, 13 retrospective cohort studies, and 3 meta-analyses). RESULTS: TT + pCCND was found to detect occult lymph node metastasis in approximately 50% of patients who had no clinical evidence of lymph node metastasis on preoperative imaging. Permanent hypoparathyroidism occurs more frequently following TT + pCCND (TT = 1.55% vs. TT + pCCND = 3.45%), but the rates of permanent recurrent laryngeal nerve dysfunction are similar (TT = 0.89% vs. TT + pCCND = 0.96%). The locoregional recurrence rates across all 14 studies included in this analysis was 6.75% for TT alone and 4.55% for TT + pCCND. The rate of locoregional recurrence was significantly lower in patients who underwent pCCND in a few studies and one meta-analysis, but were not significantly different in the majority of studies. CONCLUSIONS: TT + pCCND in clinically node negative papillary thyroid cancer will detect occult lymph node metastasis in approximately half of patients. This may change their postoperative management with regard to adjuvant radioiodine therapy. There is a higher risk of hypoparathyroidism with pCCND, and the effect on rates of locoregional recurrence remains uncertain. PMID- 29786127 TI - Crystal Ball or Magic8 Ball? Reply Hazy, Try Again. PMID- 29786128 TI - Long-Term Oncologic Outcomes of Laparoscopic Sentinel Node Navigation Surgery in Early Gastric Cancer: A Single-Center, Single-Arm, Phase II Trial. AB - BACKGROUND: Sentinel node navigation surgery (SNNS) in early gastric cancer (EGC) is technically feasible according to previous literature, however its long-term oncologic safety has not been reported. METHODS: A single-center, single-arm, phase II trial was conducted to determine the oncologic outcomes of laparoscopic sentinel node (SN) biopsy in clinical stage T1N0M0 gastric cancer patients. Cases with positive SNs on intraoperative pathologic examination underwent conventional gastrectomy with radical lymphadenectomy (SN-positive group), whereas those with negative SNs underwent laparoendoscopic-limited gastric resections without further lymph node dissections (SN-negative group). The primary endpoint was 3 year relapse-free survival. RESULTS: Between July 2010 and April 2013, 113 patients were enrolled, with 100 patients being included in the final analysis. SNs were detected in 99 patients. The mean number of identified SNs was 6.1 +/- 3.9. Eleven patients were included in the SN-positive group and 89 in the SN negative group. After a median follow-up period of 46.4 months, four patients died and three showed cancer recurrence. All recurrences occurred on the remnant stomach after endoscopic submucosal resection or wedge resection in the SN negative group. The 3-year relapse-free and overall survival rates were 96.0% (95% confidence interval [CI] 92.2-100.0%) and 98.0% (95% CI 95.2-100.0%), respectively. CONCLUSIONS: Our results indicate that laparoscopic SNNS may be oncologically safe in EGC. Limited gastric resections should be carefully performed to prevent local recurrence in SN-negative cases. A randomized controlled trial is needed based on the present study. PMID- 29786130 TI - RAS Mutation is Associated with Unsalvageable Recurrence Following Hepatectomy for Colorectal Cancer Liver Metastases. AB - BACKGROUND: RAS mutation status predicts survival after hepatectomy for colorectal liver metastases (CRLM) and survival after repeat hepatectomy for intrahepatic recurrence. This study was aimed at determining the impact of RAS mutation on amenability of recurrence to local therapy and on post-recurrence survival following hepatectomy. METHODS: CRLM patients with recurrence at any location after curative intent hepatectomy during the period 2006-2015 were retrospectively analyzed. Factors associated with recurrence not amenable to local therapy and with post-recurrence survival were evaluated. RESULTS: Of 566 patients with recurrence, 309 (54.6%) underwent chemotherapy only, 189 (33.4%) underwent surgical resection, 47 (8.3%) underwent ablation, and 21 (3.7%) underwent radiation therapy. Median post-recurrence survival was significantly longer in patients with local therapy than in those with chemotherapy only (65.1 vs. 26.5 months, p < 0.0001). RAS mutation (p = 0.01), presence of extrahepatic metastases (p = 0.0006), and positive surgical margin at prior hepatectomy (p = 0.01) were associated with recurrence not amenable to local therapy. RAS mutation [hazard ratio (HR) 1.49, p = 0.0012], disease-free interval < 12 months (HR 1.76, p < 0.0001), recurrence at multiple organs (HR 1.71, p < 0.0001), and recurrence not amenable to local therapy (HR 4.11, p < 0.0001) were independent risk factors for shorter post-recurrence survival. RAS mutation was associated with poor post recurrence survival in both patients who received local therapy and those who received chemotherapy only. CONCLUSIONS: RAS mutation predicts recurrence not amenable to any local therapy and shorter post-recurrence survival after hepatectomy for CRLM. PMID- 29786129 TI - Surgeon Variability and Factors Predicting for Reoperation Following Breast Conserving Surgery. AB - BACKGROUND: Reoperation after breast-conserving surgery (BCS) is common and has been partially associated with the lack of consensus on margin definition. We sought to investigate factors associated with reoperations and variation in reoperation rates across breast surgeons at our cancer center. METHODS: Retrospective analyses of patients with clinical stage I-II breast cancer who underwent BCS between January and December 2014 were conducted prior to the recommendation of 'no ink on tumor' margin. Patient demographics and tumor and surgical data were extracted from medical records. A multivariate regression model was used to identify factors associated with reoperation. RESULTS: Overall, 490 patients with stage I (n = 408) and stage II (n = 89) breast cancer underwent BCS; seven patients had bilateral breast cancer and underwent bilateral BCS procedures. Median invasive tumor size was 1.1 cm, reoperation rate was 22.9% (n = 114) and varied among surgeons (range 15-40%), and, in 100 (88%) patients, the second procedure was re-excision, followed by unilateral mastectomy (n = 7, 6%) and bilateral mastectomy (n = 7, 6%). Intraoperative margin techniques (global cavity or targeted shaves) were utilized in 50.1% of cases, while no specific margin technique was utilized in 49.9% of cases. Median total specimen size was 65.8 cm3 (range 24.5-156.0). In the adjusted model, patients with multifocal disease were more likely to undergo reoperation [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.17-15.42]. In addition, two surgeons were found to have significantly higher reoperation rates (OR 6.41, 95% CI 1.94-21.22; OR 3.41, 95% CI 1.07-10.85). CONCLUSIONS: Examination of BCS demonstrated variability in reoperation rates and margin practices among our breast surgeons. Future trials should look at surgeon-specific factors that may predict for reoperations. PMID- 29786131 TI - CA19-9 on Postoperative Surveillance in Pancreatic Ductal Adenocarcinoma: Predicting Recurrence and Changing Prognosis over Time. AB - BACKGROUND: Serum carbohydrate antigen 19-9 (CA19-9) correlates with response to therapy and overall survival (OS) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to define the chronologic relationship between CA19-9 elevation and radiographic recurrence to develop a model that can predict the risk of recurrence (RFS) and prognosis during interval surveillance for patients with resected PDAC. METHODS: A retrospective review examined patients undergoing surgery for pancreatic adenocarcinoma from January 2010 to May 2016. Their CA19-9 levels were classified at diagnosis, after surgery, and at 6-month surveillance intervals. Recurrence was defined by radiographic evidence. The CA19-9 levels were correlated with RFS and OS at every time point using multivariate analysis. RESULTS: The study examined 525 patients. Five patterns of CA19-9 were identified: normal ("nonsecretors," 18.5%), always elevated, and high at diagnosis but normal after resection involving three patterns with varied behavior during surveillance. These five patterns had implications for RFS and OS. When elevation of CA19-9, as assessed at 6-month intervals, was analyzed relative to detection of radiographic disease, CA19-9 had poor positive predictive value (average, 35%) but high negative predictive value (average, 92%) for radiographic recurrence. Conditional RFS showed that CA19-9 elevation did not equal radiographic recurrence but predicted subsequent RFS. Additionally, conditional OS showed that CA19-9 elevation alone was predictive at each time point. CONCLUSION: This study showed that CA19-9 patterns beyond the post resection period predict RFS and OS. High CA19-9 frequently is discordant with recurrence on imaging and may precede it by more than 6 months. At each surveillance interval, CA19-9 is predictive of prognosis, which may help in counseling patients and could be used to direct protocols of salvage chemotherapy. PMID- 29786133 TI - Editorial: Effectiveness Research in Couple and Family Therapy. PMID- 29786132 TI - The Economic Case for a Pandemic Fund. AB - The rapid urban spread of Ebola virus in West Africa in 2014 and consequent breakdown of control measures led to a significant economic impact as well as the burden on public health and wellbeing. The US government appropriated $5.4 Billion for FY2015 and WHO proposed a $100 Million emergency fund largely to curtail the threat of future outbreaks. Using epidemiological analyses and economic modeling, we propose that the best use of these and similar funds would be to serve as global insurance against the continued threat of emerging infectious diseases. An effective strategy would involve the initial investment in strengthening mobile and adaptable capacity to deal with the threat and reality of disease emergence, coupled with repeated investment to maintain what is effectively a 'national guard' for pandemic prevention and response. This investment would create a capital stock that could also provide access to safe treatment during and between crises in developing countries, lowering risk to developed countries. PMID- 29786134 TI - Early receptive language comprehension ability in children with cerebral palsy. PMID- 29786135 TI - Scientific update on nanoparticles in dentistry. AB - Nanoparticles having a size from 1 to 100 nm are present in nature and are successfully used in many products of daily life. In dental materials, nanoparticles are typically embedded but they may also exist as by-products from milling processes. Possible adverse effects of nanoparticles have gained increased interest, with the lungs being the main target organ. Exposure to nanoparticles in the dental laboratory is addressed by legal regulations. In dental practice, nanoparticles are mainly produced by intra-oral grinding/polishing and removal of materials, by wear of restorations or release from dental implants. Based on worst-case mass-based calculations, the additional risk as a result of exposure to nanoparticles is considered to be low. However, more research is needed, especially on vulnerable groups (patients with asthma or chronic obstructive pulmonary disease). An assessment of risks for the environment is not possible because of lack of data. Exposure-reduction measures mainly include avoidance of abrasive processes (for example, by proper sculpturing), cooling by the use of water spray and sufficient ventilation of treatment areas. PMID- 29786136 TI - Temporal trends in the epidemiology of cervical cancer in South Africa (1994 2012). AB - Cervical cancer (CC) is the leading cause of cancer death among female South Africans (SA). Improved access to reproductive health services following multi ethnic democracy in 1994, HIV epidemic, and the initiation of CC population-based screening in early 2000s have influenced the epidemiology of CC in SA. We therefore evaluated the trends in CC age-standardised incidence (ASIR) (1994 2009) and mortality rates (ASMR) (2004-2012) using data from the South African National Cancer Registry and the Statistics South Africa, respectively. Five-year relative survival rates and average per cent change (AAPC) stratified by ethnicity and age-groups was determined. The average annual CC cases and mortalities were 4,694 (75,099 cases/16 years) and 2,789 (25,101 deaths/9 years), respectively. The ASIR was 22.1/100,000 in 1994 and 23.3/100,000 in 2009, with an average annual decline in incidence of 0.9% per annum (AAPC = -0.9%, p-value < 0.001). The ASMR decreased slightly by 0.6% per annum from 13.9/100,000 in 2004 to 13.1/100,000 in 2012 (AAPC = -0.6%, p-value < 0.001). In 2012, ASMR was 5.8 fold higher in Blacks than in Whites. The 5-year survival rates were higher in Whites and Indians/Asians (60-80%) than in Blacks and Coloureds (40-50%). The incidence rate increased (AAPC range: 1.1-3.1%, p-value < 0.001) among young women (25-34 years) from 2000 to 2009. Despite interventions, there were minimal changes in overall epidemiology of CC in SA but there were increased CC rates among young women and ethnic disparities in CC burden. A review of the CC national policy and directed CC prevention and treatment are required to positively impact the burden of CC in SA. PMID- 29786138 TI - Association of different immunosuppressive medications with periodontal condition in patients with rheumatoid arthritis: Results from a cross-sectional study. AB - BACKGROUND: The aim of this cross-sectional study was to investigate clinical periodontal findings as well as prevalence of selected potentially periodontal pathogenic bacteria in patients with rheumatoid arthritis (RA) treated with different immunosuppressive rheumatic medications. METHODS: One hundred sixty eight patients with RA undergoing different immunosuppressive medications were included and divided into subgroups according to their medication, which was taken in the past 6 months, in detail, 1) non-steroidal anti-inflammatory drugs (NSAID) and glucocorticoids combined, and the following different disease modifying anti-rheumatic drugs (DMARDs): 2) methotrexate (MTX), 3) leflunomide, 4) MTX and TNF-alpha antagonists combined, 5) interleukin-6 (IL-6) antagonist, 6) MTX and rituximab combined, and 7) combination therapies of > 2 of these DMARDs. Periodontal examination consisted of papilla bleeding index (PBI), periodontal status with periodontal probing depth (PD), bleeding on probing (BOP), and clinical attachment loss (AL). Periodontitis was classified as none/mild, moderate, or severe. Samples obtained from gingival crevicular fluid were analyzed for presence of 11 periodontal pathogenic bacteria. RESULTS: Patients with MTX + TNF-alpha antagonists therapy showed higher PBI and BOP values compared with leflunomide (P < 0.01) and higher BOP than MTX + rituximab (P = 0.02). Porphyromonas gingivalis (P < 0.01), Treponema denticola (P < 0.01), Fusobacterium nodatum (P = 0.02) and Capnocytophaga species (P = 0.05) was associated with medication subgroup, whereby post hoc testing confirmed singular differences for several medication subgroups. CONCLUSIONS: RA medication is associated with periodontal inflammation, without differences in periodontal disease severity. Thereby, combination of MTX + TNF-alpha shows an increased potential to periodontal inflammation. Additionally, several differences in prevalence of selected bacteria were detected. PMID- 29786137 TI - Longitudinal growth of receptive language in children with cerebral palsy between 18 months and 54 months of age. AB - AIM: We examined receptive language developmental trajectories between 18 months and 54 months for three clinical speech-language profile groups of children with cerebral palsy (those with speech motor involvement, without speech motor involvement, and with anarthria) and quantified differences from age-level expectations. We identified latent classes of comprehension development, related these classes to clinical profile groups, and examined how well early receptive language predicted outcomes. METHOD: We used a prospective longitudinal design. Eighty-five children with cerebral palsy (43 females, 42 males) were followed longitudinally from 18 to 54 months of age. Children were seen two to eight times (322 data points). Children were classified into clinical profile groups. Language comprehension age-equivalent scores were the primary measures of interest. RESULTS: Children with anarthria had significant language delays, limited developmental change over time, and comprised their own latent class. Children with speech motor impairment had slight receptive language delays over time. Children with no speech motor impairment had age-appropriate receptive language over time. Early language comprehension scores were highly predictive of later latent profile group membership. INTERPRETATION: Early language comprehension abilities are highly predictive of language comprehension growth trajectory and suggest that children with early language delay, particularly those who are non-speaking, should receive language intervention to support development. WHAT THIS PAPER ADDS: There are two growth trajectories for language comprehension among children with cerebral palsy. Children with speech motor impairment had a constant 6-month receptive language delay. Children without speech motor impairment had age-appropriate receptive language. Non-speaking children had significant receptive language delay. Early language comprehension change was highly predictive of later trajectory group. PMID- 29786139 TI - One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. AB - One-carbon metabolism biomarkers are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1190 matched controls. Total B vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5'-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Additionally, associations with CRC risk were similar for the ratio-based B vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status). In conclusion, ratio-based B-vitamin markers were good predictors of total B-vitamin status and displayed similar associations as total B-vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice. This article is protected by copyright. All rights reserved. PMID- 29786140 TI - Gender differences in the association of periodontitis and type 2 diabetes. AB - AIMS: THE OBJECTIVE WAS TO INVESTIGATE IF GENDER DIFFERENCES EXIST IN THE ASSOCIATIONS BETWEEN PERIODONTITIS AND TYPE 2 DIABETES. DISPROPORTIONATE DISPARITIES BY GENDER WERE FOUND TO EXIST IN RATES OF BOTH PERIODONTITIS AND DIABETES WITH RESPECT TO DEMOGRAPHICS AND BEHAVIOURAL PREDICTORS THAT CANNOT BE EXPLAINED SOLELY BY THE WELL-ESTABLISHED ASSOCIATION BETWEEN THESE TWO DISEASES. MATERIALS AND METHODS: MULTIPLE DATASETS WERE EXTRACTED FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES) 2009-2014, WHICH USED A STRATIFIED MULTISTAGE PROBABILITY SAMPLING TO OBTAIN SAMPLES FROM ALL CIVILIAN NON INSTITUTIONALISED PEOPLE IN THE USA. BIVARIATE RELATIONSHIPS BETWEEN EACH EXPLANATORY VARIABLE AND PERIODONTITIS LEVEL WERE ASSESSED WITH ODDS RATIOS (OR) AND THEIR 95% CONFIDENCE INTERVALS (CI). A SET OF WEIGHTED LOGISTIC REGRESSION MODELS WAS USED TO INVESTIGATE THE ASSOCIATION DIFFERENTIATIONS BETWEEN PERIODONTITIS AND DIABETES BY GENDER. C-STATISTICS MEASURED THE GOODNESS-OF-FIT OF WEIGHTED LOGISTIC REGRESSION MODELS. RESULTS: THE PREVALENCE OF MODERATE SEVERE PERIODONTITIS WAS 36.39% AND 22.71% AMONG PARTICIPANTS WITH TYPE 2 DIABETES AND WITHOUT DIABETES, RESPECTIVELY. TYPE 2 DIABETES WAS SIGNIFICANTLY ASSOCIATED WITH MODERATE-SEVERE PERIODONTITIS OR (OR = 1.47, 95% CI: 1.18-1.82) AMONG MALES EVEN AFTER ADJUSTING FOR DEMOGRAPHICS, SOCIOECONOMIC STATUS AND ORAL HEALTH BEHAVIOURS. THE AFOREMENTIONED RELATIONSHIP WAS NOT FOUND IN FEMALES. FURTHERMORE, DIFFERENT RELATIONSHIPS OF MODERATE-SEVERE PERIODONTITIS WITH BODY MASS INDEX AND THE USE OF MOUTHWASH WERE FOUND BETWEEN THE MALES AND FEMALES. CONCLUSIONS: THE CURRENT FINDINGS SUGGEST THAT IMPORTANT IMPROVEMENTS IN THE DEVELOPMENT OF GENDER-SPECIFIC STRATEGIES IN PREVENTION, SUCH AS ORAL HOME-CARE, TO REDUCE THE HIGH PREVALENCE OF PERIODONTAL DISEASE AND MAINTAIN GOOD ORAL HEALTH ARE VITAL, AND ARE ESPECIALLY IMPORTANT FOR MALE DIABETIC PATIENTS AND THOSE WHO ARE AT HIGH RISK OF DEVELOPING DIABETES, SUCH AS THOSE WHO ARE OBESE. PMID- 29786142 TI - The bone marrow is not only a primary lymphoid organ: The critical role for T lymphocyte migration and housing of long-term memory plasma cells. AB - In immunology and anatomy textbooks the bone marrow is described as a typical "primary lymphoid organ" producing lymphoid cells independent of antigens. The hematopoietic bone marrow is largely age-dependent organ with great anatomical and functional differences among various species. There are estimates that about 12% of all lymphoid cells in the human body are found in the bone marrow at any given time (2% in the peripheral blood). Enormous numbers of T lymphocytes migrate to the bone marrow and partly return later to the blood. Many of these lymphocytes are memory CD4+ and CD8+ T cells. A few days after immunization a wave of plasma cells and their precursors migrate to the bone marrow where they lose their migratory response to CXCL-12 and CXCL9. There is a relative enrichment of CD19+ B cells in the bone marrow outnumbering those in the blood and secondary lymphoid organs. This is not due to local production. The proliferation and migration kinetics of these lymphoid cells in the bone marrow have to be studied in more detail as this is of major clinical relevance. PMID- 29786141 TI - An inhibitory antibody targeting carbonic anhydrase XII abrogates chemoresistance and significantly reduces lung metastases in an orthotopic breast cancer model in vivo. AB - Carbonic anhydrase XII (CAXII) is a membrane-tethered ectoenzyme involved in intracellular pH regulation and overexpressed across various types of human cancer. Because CAXII inhibition shows antitumor activity in vitro, it is thought that the enzyme is mandatory for maximum tumor growth, above all under hypoxic conditions. Recently, it has been shown that CAXII is co-expressed along with the P-glycoprotein (P-GP) on many tumor cells and that both proteins physically interact. Of interest, blocking CAXII activity also decreases P-GP activity in cancer cells both in vitro and in vivo. Previously, we have reported on the development of a monoclonal antibody, termed 6A10, which specifically and efficiently blocks human CAXII activity. Here, we demonstrate that 6A10 also indirectly reduces P-GP activity in CAXII/P-GP double-positive chemoresistant cancer cells, resulting in enhanced chemosensitivity as revealed by enhanced accumulation of anthracyclines and increased cell death in vitro. Even more important, we show that mice carrying human triple-negative breast cancer xenografts co-treated with doxorubicin (DOX) and 6A10 show a significantly reduced number of metastases. Collectively, our data provide evidence that the inhibition of CAXII with 6A10 is an attractive way to reduce chemoresistance of cancer cells and to interfere with the metastatic process in a clinical setting. PMID- 29786143 TI - Impact of commensal flora on periodontal immune response to lipopolysaccharide. AB - BACKGROUND: Commensal flora are involved in the appropriate development of the mature immune system. However, it is unclear how commensal flora contribute to immune responses against periodontal pathogens, including the response to lipopolysaccharide (LPS). The purpose of this study was to evaluate the expression of immune responses after topical application of LPS in germ-free (GF) and specific-pathogen-free (SPF) mice. METHODS: GF and SPF mice at 8 weeks of age were randomly divided into four groups each: a baseline group (n = 4/group) and three experimental groups (n = 6/group). Experimental groups received topical application of Porphyromonas gingivalis LPS (10 MUg/MUL) into the palatal gingival sulcus. Sampling was performed before LPS application (baseline) and at 3, 24, or 72 hours after LPS application. The numbers of neutrophils, CD4+ , and CD8+ T cells in periodontal tissue were evaluated by immunohistochemistry. Expression of genes encoding cytokines, chemokines, and a transcription factor was determined by real-time PCR. RESULTS: SPF mice, but not GF mice, showed an increased number of CD4+ T cells in the periodontal tissue at 3 hours after LPS application, compared with the number at baseline (p < 0.05). Gene expressions of tumor necrosis factor-alpha (Tnf-alpha) and forkhead box protein p3 (Foxp3) was also significantly higher in the SPF mice than in the GF mice at 3 hours after LPS application (p < 0.05). The number of neutrophils peaked at 24 hours in both GF and SPF mice. CONCLUSIONS: LPS-exposed SPF mice exhibited increases in the number of CD4+ T cells and in Tnf-alpha and Foxp3 gene expression in periodontal tissue compared with LPS-exposed GF mice. PMID- 29786144 TI - Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. AB - Epidermolysis bullosa is a rare blistering skin disorder that is challenging to manage because skin fragility and repeated wound healing cause itching, pain, limited mobility, and recurrent infections. Cannabidiol, an active cannabinoid found in cannabis, is postulated to have antiinflammatory and analgesic effects. We report 3 cases of self-initiated topical cannabidiol use in patients with epidermolysis bullosa in an observational study. One patient was weaned completely off oral opioid analgesics. All 3 reported faster wound healing, less blistering, and amelioration of pain with cannabidiol use. Although these results demonstrate promise, further randomized, double-blind clinical trials are necessary to provide scientific evidence of our observed benefits of cannabidiol for the treatment of epidermolysis bullosa. PMID- 29786145 TI - Pilot study demonstrates that placental histology can provide an additional tool for diagnosing early-onset neonatal sepsis. AB - AIM: We explored whether placental histology could help to diagnose early-onset neonatal sepsis (EONS), guide clinical decision-making 48 hours after birth and reduce antibiotic use. METHODS: This study comprised 109 infants born at less than 32 weeks of gestation, who were admitted to the neonatal intensive care unit of Isala, Zwolle, The Netherlands, between January 2013 and December 2013. EONS was defined as clinical symptoms plus raised serial C-reactive protein (CRP) >10 mg/L and a positive (proven EONS) or a negative (suspected EONS) blood culture. Placentas were studied for a histological inflammatory response and scored according to Redline's criteria. RESULTS: A histological inflammatory response was seen in 15/88 (17%) placentas and this occurred significantly more often in infants with a high suspicion of EONS (p < 0.05). No histological inflammatory response was seen if maternal risk factors for EONS were absent, despite a raised CRP level. Based on placental histology, the duration of antibiotic therapy was reduced from more than five days to 48 hours in 20/27 infants (74%). CONCLUSION: Histological examination of the placenta helped to diagnose EONS and guide clinical decision-making 48 hours after birth and led to a clinically relevant reduction in antibiotic use. PMID- 29786146 TI - Awareness of and phobias about topical corticosteroids in parents of infants with eczema in Hangzhou, China. AB - BACKGROUND/OBJECTIVES: Knowledge of and phobias about topical corticosteroids in parents of infants with eczema affect efficacy of eczema treatment. METHODS: We surveyed 300 parents of children with eczema using a questionnaire to investigate knowledge of and phobias about topical corticosteroids. RESULTS: Overall, 85.7% (n = 257) of children had used topical corticosteroids, with 12.8% (n = 33) of children having steroids applied for only 1-3 days per episode; 79.4% (n = 204) of patients discontinued topical steroid therapy immediately after improvement. Twenty-five percent (n = 75) of parents refused a prescription of steroid ointment, and 32.3% (n = 97) did not use the steroid ointment on their children despite having received a prescription. During steroid treatment, 95.7% (246) of parents were very concerned about the side effects of topical steroids. One hundred eight parents (42%) did not use a topical steroid ointment for recurrence of eczema because of concerns about using topical corticosteroids. CONCLUSION: Most parents of infants with eczema had excessive concerns about topical corticosteroids, leading to inadequate treatment of atopic dermatitis. In clinical practice, physicians should reinforce parents' understanding of steroid treatment for eczema and guide rational use of topical steroids for infantile eczema. PMID- 29786147 TI - Timing and frequency of sublethal exposure modifies the induction and retention of increased insecticide tolerance in wood frogs (Lithobates sylvaticus). AB - Although the paradigm for increased tolerance to pesticides has been by selection on constitutive (naive) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures. To test these hypotheses, we exposed wood frog tadpoles to either a no carbaryl control (water) or 0.5 mg/L carbaryl at 4 time periods, and later tested their tolerance to carbaryl using time-to-death assays. We discovered that tadpoles induced increased tolerance early and midway but not late in our experiment and their constitutive tolerance increased with age. We found no difference in the magnitude of induced tolerance after a single or 2 exposures. Finally, induced pesticide tolerance was reversed within 6 d but was retained only when tadpoles experienced all 4 consecutive exposures. Phenotypic plasticity provides an immediate response for sensitive amphibian larvae to early pesticide exposures and reduces phenotypic mismatches in aquatic environments contaminated by agrochemicals. Environ Toxicol Chem 2018;37:2188-2197. (c) 2018 SETAC. PMID- 29786148 TI - Ecotoxicological Assessment of Immersion Samples from Facade Render Containing Free or Encapsulated Biocides. AB - To protect house facades from fouling by microorganisms, biocides can be added to a render or paint before it is applied. During driving rain events, these biocides gradually leach out and have the potential to pollute soil or aquatic ecosystems. We studied the leaching behavior of biocides and toxicity of leachates from renders with either free or encapsulated biocides. Both render types contained equal amounts of terbutryn, 2-octyl-3(2H)-isothiazolinone (OIT), and 4,5-dichloro-2-n-octyl-4-isothiazolino-3-one (DCOIT). Nine leachate samples were generated over 9 immersion cycles according to a European standard, and biocides were quantified. The first and ninth leachate samples were tested using bioassays with algae, bacteria, and water fleas, the first sample was also tested with earthworms and springtails. Encapsulation reduced leaching of terbutryn, OIT, and DCOIT by 4-, 17-, and 27-fold. For aquatic organisms, the toxicity of water from render containing encapsulated biocides was always lower than that of render with free biocides. Furthermore, toxicity decreased by 4- to 5-fold over the 9 immersion cycles. Inhibition of photosynthesis was the most sensitive endpoint, followed by algal growth rate, bacterial bioluminescence, and water flea reproduction. Toxicity to algae was due to terbutryn and toxicity to bacteria was due to OIT. None of the samples affected soil organisms. Results demonstrate that combining standardized leaching tests with standardized bioassays is a promising approach to evaluate the ecotoxicity of biocides that leach from facade renders. Environ Toxicol Chem 2018;37:2246-2256. (c) 2018 SETAC. PMID- 29786149 TI - National survey found that managing childhood nephrotic syndrome in Nigeria varied widely and did not comply with the best evidence. AB - AIM: This study explored any variations in managing childhood nephrotic syndrome between specialist centres in Nigeria and how closely the care reflected the best available evidence. METHODS: In 2016, the heads of Nigerian paediatric nephrology units were asked to complete a study questionnaire that focused on managing nephrotic syndrome. RESULTS: Of the 31 clinicians we approached, 81% returned the completed questionnaire. The majority (64%) had received paediatric nephrology training and 40% had practised for at least 10 years. We found that 60% prescribed an initial daily prednisolone for four weeks before reducing the dose and 32% prescribed it for six weeks. However, more marked variations were observed with the total steroid duration for new-onset nephrotic syndrome, with 16%, 44% and 40% prescribing prednisolone for 8, 12 and at least 16 weeks, respectively. Similarly, 56% prescribed prednisolone for less than eight weeks before diagnosing steroid-resistant nephrotic syndrome (SRNS) and 12% rarely requested a kidney biopsy for SRNS. In addition, 32% of the respondents preferred cyclophosphamide to calcineurin inhibitors for SRNS. CONCLUSION: There were significant variations in the management of childhood nephrotic syndrome in Nigeria and the diagnosis and treatment of SRNS differed substantially from the best available evidence. PMID- 29786150 TI - Stem cells, blood vessels, and angiogenesis as major determinants for musculoskeletal tissue repair. AB - This manuscript summarizes 20 years of research from my laboratories at the University of Pittsburgh and more recently, at the University of Texas Health Science Center at Houston and the Steadman Philippon Research Institute in Vail, Colorado. The discovery of muscle-derived stem cells (MDSCs) did not arise from a deliberate search to find a novel population of muscle cells with high regenerative potential, but instead was conceived in response to setbacks encountered while working in muscle cell transplantation for Duchenne muscular dystrophy (DMD). DMD is a devastating inherited X-linked muscle disease characterized by progressive muscle weakness due to lack of dystrophin expression in muscle fiber sarcolemma. Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin, this approach has been hindered by limited survival (less than 1%) of the injected cells. The fact that 99% of the cells were not surviving implantation was seen as a major weakness with this technology by most. My research team decided to investigate which cells represent the 1% of the cells surviving post-implantation. We have subsequently confirmed that the few cells which exhibit high survival post-implantation also display stem cell characteristics, and were termed "muscle-derived stem cells" or MDSCs. Herein, I will describe the origin of these MDSCs, the mechanisms of MDSC action during tissue repair, and finally the development of therapeutic strategies to improve regeneration and repair of musculoskeletal tissues. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2018. PMID- 29786151 TI - Time dependent loss of trabecular bone in human tibial plateau fractures. AB - We investigated if time between injury and surgery affects cancellous bone properties in patients suffering tibial plateau fractures (TPF), in terms of structural integrity and gene expression controlling bone loss. A cohort of 29 TPF, operated 1-17 days post-injury, had biopsies from the fracture and an equivalent contralateral limb site, at surgery. Samples were assessed using micro computed tomography and real-time RT-PCR analysis for the expression of genes known to be involved in bone remodeling and fracture healing. Significant decreases in the injured vs control side were observed for bone volume fraction (BV/TV, -13.5 +/- 6.0%, p = 0.011), trabecular number (Tb.N, -10.5 +/- 5.9%, p = 0.041) and trabecular thickness (Tb.Th, -4.6 +/- 2.5%, p = 0.033). Changes in these parameters were more evident in patients operated 5-17 days post-injury, compared to those operated in the first 4 days post-injury. A significant negative association was found between Tb.Th (r = -0.54, p < 0.01) and BV/TV (r = -0.39, p < 0.05) in relation to time post-injury in the injured limb. Both BV/TV and Tb.Th were negatively associated with expression of key molecular markers of bone resorption, CTSK, ACP5, and the ratio of RANKL:OPG mRNA. These structure/gene expression relationships did not exist in the contralateral tibial plateau of these patients. This study demonstrated that there is a significant early time-dependent bone loss in the proximal tibia after TPF. This bone loss was significantly associated with altered expression of genes typically involved in the process of osteoclastic bone resorption but possibly also bone resorption by osteocytes. The mechanism of early bone loss in such fractures should be a subject of further investigation. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID- 29786152 TI - Ureteral endometriosis: Correlation between ultrasonography and laparoscopy. AB - Ultrasound for deep infiltrating endometriosis was shown to be at least as accurate as magnetic resonance although the largest efforts aimed at evaluating the posterior pelvic compartment1 . The lateral pelvic compartment is less studied although endometriosis of the broad ligaments represents the most frequent site where endometriosis lies in advanced stages2 . This article is protected by copyright. All rights reserved. PMID- 29786153 TI - Vasa previa screening strategies: decision and cost-effectiveness analysis. AB - OBJECTIVE: To perform a decision and cost-effectiveness analysis comparing four screening strategies for the antenatal diagnosis of vasa previa in singleton pregnancies. METHODS: A decision-analytic model was constructed comparing vasa previa screening strategies. Published probabilities and costs were applied to four transvaginal screening scenarios that were carried out at the time of mid trimester ultrasound: no screening, ultrasound-indicated screening, screening only pregnancies conceived by in-vitro fertilization (IVF) and universal screening. Ultrasound-indicated screening was defined as performing transvaginal ultrasound at the time of the routine anatomy ultrasound scan in response to one of the following sonographic findings associated with an increased risk of vasa previa: low-lying placenta, marginal or velamentous cord insertion or bilobed or succenturiate lobed placenta. The primary outcome was cost per quality-adjusted life year (QALY) in US$. The analysis was performed from a healthcare system perspective with a willingness-to-pay threshold of $100 000 per QALY selected. One-way and multivariate sensitivity analysis (Monte-Carlo simulation) was performed. RESULTS: This decision-analytic model demonstrated that screening pregnancies conceived by IVF was the most cost-effective strategy, with an incremental cost effectiveness ratio (ICER) of $29186.50/QALY. Ultrasound indicated screening was the second most cost-effective, with an ICER of $56096.77/QALY. These data were robust to all one-way and multivariate sensitivity analyses performed. CONCLUSIONS: Within the baseline assumptions, transvaginal ultrasound screening for vasa previa appears to be most cost effective when performed among IVF pregnancies. However, both IVF and ultrasound indicated screening strategies fall within contemporary willingness-to-pay thresholds, suggesting that both strategies may be appropriate to apply in clinical practice. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd. PMID- 29786154 TI - Topical polyhydroxy acid treatment for autosomal recessive congenital ichthyosis in the golden retriever: a prospective pilot study. AB - BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) in golden retrievers is due to a PNPLA1 gene mutation, which plays a role in epidermal lipid organization and metabolism. Topical therapies are used to reduce scaling; however, there are few published efficacy studies. OBJECTIVES: To examine the efficacy of topical treatment based on gluconolactone, a polyhydroxy acid with known beneficial effects on stratum corneum structure. ANIMALS: Sixteen golden retriever dogs with clinical signs of ARCI and PCR-confirmed PNPLA1 gene mutation. METHODS: This was a prospective, multicentre, noncontrolled study. Dogs were treated with a shampoo and lotion containing gluconolactone and other hydroxyl acids. Treatments were administered initially twice weekly for two weeks, then once weekly for two weeks and finally once monthly. Examinations were performed prior to and at 14 and 30 days of treatment to assess scaling, presence of other skin lesions and pruritus. In two dogs, pre- and 30 day post-treatment, skin biopsies were obtained. RESULTS: The extent and size of the scales were reduced by 60% and 75% after 14 and 30 days of treatment, respectively (P < 0.001). In 20% of the dogs, scaling was no longer observed after the first 30 days of treatment. No other skin lesions or pruritus were observed in any dog. Post-treatment biopsies showed normalization of the stratum corneum morphology and reduced hyperpigmentation. CONCLUSION AND CLINICAL IMPORTANCE: The frequent use of a shampoo and lotion containing gluconolactone may be an effective measure to improve skin scaling in golden retrievers with ARCI. PMID- 29786155 TI - Is home blood-pressure monitoring in hypertensive disorders of pregnancy consistent with clinic recordings? AB - OBJECTIVE: To assess the agreement between home blood-pressure monitoring (HBPM) and blood-pressure measurements in a clinic setting, in a cohort of pregnant women with hypertensive disorders of pregnancy (HDP). METHODS: This was a cohort study of 147 pregnant women with HDP conducted at St George's Hospital, University of London, London, UK, between 2016 and 2017. Inclusion criteria were chronic hypertension, gestational hypertension or high risk of developing pre eclampsia, no significant proteinuria and no hematological or biochemical abnormalities. Each included patient was prescribed a personalized schedule of hospital visits and blood-pressure measurements, according to their individual risk as per UK National Institute for Health and Care Excellence guidelines. The blood-pressure measurement at the clinic and the HBPM reading obtained closest to that hospital visit were paired for analysis. Only one pair of measurements was used per patient. Differences between home and clinic blood-pressure measurements were tested using the Wilcoxon signed rank test or paired t-test, and were also assessed visually using Bland-Altman plots. Comparison of the binary outcomes was performed using McNemar's chi-square test. Subgroup analysis was performed in the following gestational-age windows: < 14 weeks, 15-22 weeks, 23-32 weeks and 33-42 weeks' gestation. RESULTS: A total of 294 blood-pressure measurements from 147 women were included in the analysis. Median systolic HBPM measurements were significantly lower than clinic measurements (132.0 (interquartile range (IQR), 123.0-140.0) mmHg vs 138.0 (IQR, 132.0-146.5) mmHg; P < 0.001). When stratified according to gestational age, systolic blood-pressure measurements obtained at home were significantly lower than those at clinic in all gestational-age periods except 23-32 weeks' gestation (P = 0.057). Median diastolic blood-pressure measurements at home were also significantly lower than those at clinic (85.0 (IQR, 77.0-90.0) mmHg vs 89.0 (IQR, 82.0-94.0) mmHg; P < 0.001). When stratified according to gestational age, diastolic HBPM measurements were significantly lower in the periods 5-14 weeks (P < 0.001), 15-22 weeks (P = 0.008) and 33-42 weeks (P < 0.001), compared with clinic measurements. The incidence of clinically significant systolic and diastolic hypertension based on clinic blood-pressure measurements was four to five times higher than that based on HBPM measurements (P < 0.001 and P = 0.005, respectively). CONCLUSIONS: Our study shows that, in women with HDP, blood pressure measured at home is lower than that measured in a clinic setting. This is consistent with observations in non-pregnant adults, in whom home and ambulatory monitoring of hypertensive patients is recommended. As such, HBPM has the potential to reduce the number of false-positive diagnoses of severe hypertension and unnecessary medical interventions in women with HDP. This must be carefully weighed against the risk of missing true-positive diagnoses. Prospective studies investigating the use of HBPM in pregnant women are urgently needed to determine the relevant blood-pressure thresholds for HBPM, and interval and frequency of monitoring. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd. PMID- 29786156 TI - SMAD2 as a risk locus for human left atrial isomerism detected by mother-fetus pair exome sequencing and image studies including fetal ultrasound. AB - Left atrial isomerism (LAI) is one of the two subdivisions of heterotaxy syndrome (also called situs ambiguous). It is caused by disruption of the normal left right (LR) distribution of the thoracoabdominal organs during the embryonic stage, resulting in bilateral left-sided morphology of the atrial appendages of the heart without the right-sided structures. This article is protected by copyright. All rights reserved. PMID- 29786157 TI - The antioxidants neopterin/7,8-dihydroneopterin: Novel biomarker and muscle protectant in Duchenne muscular dystrophy. PMID- 29786158 TI - Observational studies investigating hip fracture risk: a fundamental methodological issue? PMID- 29786159 TI - Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis. AB - BACKGROUND: Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. OBJECTIVE: The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. METHODS: We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. RESULTS: Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. CONCLUSIONS: This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials. PMID- 29786160 TI - Aberrant learning in Parkinson's disease: A neurocomputational study on bradykinesia. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA-induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology. The aim of this work was to investigate DA-driven aberrant learning as a concurrent cause of bradykinesia, using a comprehensive, biologically inspired neurocomputational model of action selection in the BG. The model includes the three main pathways operating in the BG circuitry, that is the direct, indirect and hyperdirect pathways, and use a two-term Hebb rule to train synapses in the striatum, based on previous history of rewards and punishments. Levodopa pharmacodynamics is also incorporated. Through model simulations of the Alternate Finger Tapping motor task, we assessed the role of aberrant learning on bradykinesia. The results show that training under drug medication (levodopa) provides not only immediate but also delayed benefit lasting in time. Conversely, if performed in conditions of vanishing levodopa efficacy, training may result in dysfunctional corticostriatal synaptic plasticity, further worsening motor performances in PD subjects. This suggests that bradykinesia may result from the concurrent effects of low DA levels and dysfunctional plasticity and that training can be exploited in medicated subjects to improve levodopa treatment. PMID- 29786161 TI - Evidence for horizontal gene transfer and separation of effector recognition from effector function revealed by analysis of effector genes shared between cape gooseberry- and tomato-infecting formae speciales of Fusarium oxysporum. AB - RNA sequencing (RNAseq) reads from cape gooseberry plants (Physalis peruviana) infected with Fusarium oxysporumf. sp. physali (Foph) were mapped against the lineage-specific transcriptome of Fusarium oxysporumf. sp. lycopersici (Fol) to look for putative effector genes. Homologues of Fol SIX1(designated SIX1a and SIX1b), SIX7, SIX10, SIX12, SIX15 and Ave1were identified. The near identity of the Foph and Fol SIX7, SIX10 and SIX12genes and their intergenic regions suggest that this gene cluster may have undergone recent lateral transfer. Foph SIX1a and SIX1bwere tested for their ability to complement a SIX1 knockout mutant of Fol. This mutant shows reduced pathogenicity on susceptible tomato plants, but is able to infect otherwise resistant tomato plants carrying the I-3 gene for Fusarium wilt resistance (SIX1 corresponds to Avr3). Neither SIX1a nor SIX1b could restore full pathogenicity on susceptible tomato plants, suggesting that any role they may play in pathogenicity is likely to be specific to cape gooseberry. SIX1b, but not SIX1a, was able to restore avirulence on tomato plants carrying I-3.These findings separate the recognition of SIX1 from its role as an effector and suggest direct recognition by I-3. A hypervariable region of SIX1undergoing diversifying selection within the F. oxysporum species complex is likely to play an important role in SIX1 recognition. These findings also indicate that I-3could potentially be deployed as a transgene in cape gooseberry to protect this emerging crop from Foph.Alternatively, cape gooseberry germplasm could be explored for I-3homologues capable of providing resistance to Foph. PMID- 29786162 TI - Hospitals and the generic versus brand-name prescription decision in the outpatient sector. AB - Health care payers try to reduce costs by promoting the use of cheaper generic drugs. We show strong interrelations in drug prescriptions between the inpatient and outpatient sectors by using a large administrative dataset from Austria. Patients with prior hospital visits have a significantly lower probability of receiving a generic drug in the outpatient sector. The size of the effect depends on both the patient and doctor characteristics, which could be related to the differences in hospital treatment and heterogeneity in the physicians' adherence to hospital choices. Our results suggest that hospital decisions create spillover costs in health care systems with separate funding for inpatient and outpatient care. PMID- 29786163 TI - Embryonal tumour of posterior cerebral fossa false-negative diagnosis by fetal MR related to misinterpretation of decreased apparent diffusion coefficient. AB - We report a case of misinterpretation of decreased apparent diffusion coefficient (ADC) on diffusion-weighted fetal MR, interpreted as a vascular clastic lesion of the posterior fossa, which turned to be caused by an embryonic hypercellular tumour. This article is protected by copyright. All rights reserved. PMID- 29786164 TI - Air Activated Self-Decontaminating Polydicyclopentadiene PolyHIPE Foams for Rapid Decontamination of Chemical Warfare Agents. AB - The threat of chemical warfare agents (CWA) compels research into novel self decontaminating materials (SDM) for the continued safety of first-responders, civilians, and active service personnel. The capacity to actively detoxify, as opposed to merely sequester, offending agents under typical environmental conditions defines the added value of SDMs in comparison to traditional adsorptive materials. Porous polymers, synthesized via the high internal phase emulsion (HIPE) templating, provide a facile fabrication method for materials with permeable open cellular structures that may serve in air filtration applications. PolyHIPEs comprising polydicyclopentadiene (polyDCPD) networks form stable hydroperoxide species following activation in air under ambient conditions. The hydroperoxide-containing polyDCPD materials react quickly with CWA simulants, Demeton-S and 2-chloroethyl ethyl sulfide, forming oxidation products as confirmed via gas chromatography mass spectrometry. The simplicity of the detoxification chemistry paired with the porous foam form factor presents an exciting opportunity for the development of self-decontaminating filter media. PMID- 29786166 TI - A label-free fluorescence method for detection of ureC gene and diagnosis of Helicobacter pylori infection. AB - The feasibility of using a polymerase chain reaction (PCR)-based label-free DNA sensor for the detection of Helicobacter pylori is investigated. In particular, H. pylori ureC gene, a specific H. pylori nucleic acid sequence, was selected as the target sequence. In the presence of ureC gene, the target DNA could be amplified to dsDNA with much higher detectable levels. After added the SYBR green I (SGI), the sensing system could show high fluorescence. Thus, the target DNA can be detected by monitoring the change of fluorescence intensity of sensing system. The clinical performance of this method was determined by comparing it with another conventional technique urea breath test (UBT). The result also showed good distinguishing ability between negative and positive patient, which was in good agreement with that obtained by the UBT. It suggests that the label free fluorescence-based method is more suitable for infection confirmation test of H. pylori. This approach offers great potential for simple, sensitive and cost effective identification of H. pylori infection. PMID- 29786165 TI - Comparative study of 1-year clinical and radiological outcomes using robot assisted pedicle screw fixation and freehand technique in posterior lumbar interbody fusion: A prospective, randomized controlled trial. AB - BACKGROUND: The purpose of this study was to compare the clinical outcome of surgery using robot-assisted posterior interbody fusion with that using freehand posterior interbody fusion in patients with degenerative spinal disease. METHODS: 78 participants with degenerative spinal disease were randomly allocated (1:1) to the minimally invasive (MIS), posterior lumbar interbody fusion (Robot-PLIF) or conventional, freehand, open-approach, posterior lumbar interbody fusion (Freehand-PLIF). RESULTS: The baseline-adjusted scores on the Oswestry Disability Index (ODI) in both groups at 1 year after surgery were not different (P = 0.688). However, the decrease in disc height at the proximal adjacent segment was significantly less in the Robot-PLIF group than in the Freehand-PLIF group (P = 0.039). CONCLUSION: One-year surgical outcomes including Visual Analog Scale, ODI and Short Form-36 did not differ between the two groups. The disc height in the proximal adjacent segment was significantly less decreased in the Robot-PLIF group than in the Freehand-PLIF group. PMID- 29786167 TI - Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks. AB - Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair. PMID- 29786168 TI - Variation in electrode redox potential selects for different microorganisms under cathodic current flow from electrodes in marine sediments. AB - Extracellular electron transport (EET) is a microbial process that allows microorganisms to transport electrons to and from insoluble substrates outside of the cell. Although progress has been made in understanding how microbes transfer electrons to insoluble substrates, the process of receiving electrons has largely remained unexplored. We investigated redox potentials favourable for donating electrons to dissolved and insoluble components in Catalina Harbor marine sediment by combining electrochemical techniques with geochemistry and molecular methods. Working electrodes buried in sediment microcosms were poised at seven redox potentials between -300 and -750 mV versus Ag/AgCl using a three-electrode system. In electrode biofilms recovered after 2-month incubations, overall community diversity increased with more negative redox potentials. Abundances of known EET-capable groups (e.g., Alteromonadales and Desulfuromonadales) varied with redox potential. Motility and chemotaxis genes were found in greater abundance in electrode communities, suggesting a possible selective advantage of these pathways for colonization and utilization of the electrode. Our enrichments demonstrated the validity of this approach in capturing groups known, as well as novel groups (e.g., Campylobacterales) that perform EET. The diverse nature of the enriched cathode communities suggest that insoluble substrate oxidation may be a critical, although poorly described microbial metabolic process in marine sediment. PMID- 29786169 TI - Bangladeshi children with acute diarrhoea show faecal microbiomes with increased Streptococcus abundance, irrespective of diarrhoea aetiology. AB - We report streptococcal dysbiosis in acute diarrhoea irrespective of aetiology. Compared with 20 healthy local controls, 71 Bangladeshi children hospitalized with acute diarrhoea (AD) of viral, mixed viral/bacterial, bacterial and unknown aetiology showed a significantly decreased bacterial diversity with loss of pathways characteristic for the healthy distal colon microbiome (mannan degradation, methylerythritol phosphate and thiamin biosynthesis), an increased proportion of faecal streptococci belonging to the Streptococcus bovis and Streptococcus salivarius species complexes, and an increased level of E. coli associated virulence genes. No enteropathogens could be attributed to a subgroup of patients. Elevated lytic coliphage DNA was detected in 2 out of 5 investigated enteroaggregative E. coli (EAEC)-infected patients. Streptococcal outgrowth in AD is discussed as a potential nutrient-driven consequence of glucose provided with oral rehydration solution. PMID- 29786170 TI - Immunopeptidomic Profiling of HLA-A2-Positive Triple Negative Breast Cancer Identifies Potential Immunotherapy Target Antigens. AB - The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilizing T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analyzed the immunopeptidomes of six HLA-A2 positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 ). Immunopeptidomic profiling identified a total of 19 675 peptides from tumor and adjacent normal tissue and 130 of the peptides were found to have higher abundance in tumor than in normal tissues. To determine potential therapeutic target proteins, we calculated the average tumor-associated cohort coverage (aTaCC) that represents the percentage coverage of each protein in this cohort by peptides that had higher tumoral abundance. Cofilin-1 (CFL-1), interleukin-32 (IL-32), proliferating cell nuclear antigen (PCNA), syntenin-1 (SDCBP), and ribophorin-2 (RPN-2) were found to have the highest aTaCC scores. We propose that these antigens could be evaluated further for their potential as targets in breast cancer immunotherapy and the small cohort immunopeptidomics analysis technique could be used in a wide spectrum of target discovery. Data are available via ProteomeXchange with identifier PXD009738. PMID- 29786171 TI - Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants. AB - It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. PMID- 29786172 TI - Serial measurements of cardiac troponin I (cTnI) in dogs treated with doxorubicin. AB - The study aimed to evaluate whether cardiac troponin I (cTnI) and pulsed-wave tissue Doppler imaging (TDI) measurements can detect cardiac changes during doxorubicin therapy in dogs with various types of cancers compared to conventional echocardiography. Serial measurements of cTnI and conventional and pulsed-wave TDI echocardiography were performed in 12 dogs diagnosed with various types of cancers at day 0, weeks 3, 6, 9, and 12 prior to each doxorubicin injection. After treatment with doxorubicin, dogs had significantly increased cTnI levels at week 9 (p = 0.027) and 12 (p = 0.027) compared to normal untreated dogs. Dogs had increased cTnI levels during doxorubicin therapy (p = 0.004). Percent left ventricular ejection fraction (LVEF) and fractional shortening (FS) assessed by 2-dimensional and M-mode echocardiography significantly decreased at weeks 9 and 12. Pulsed-wave TDI derived myocardial performance index (MPI) increased significantly at weeks 9 and 12 compared to day 0 (p = 0.028 and 0.040, respectively). In conclusion, dogs treated with doxorubicin had increased cTnI levels. An increase in cTnI levels was detected before echocardiographic value changes. Serum cTnI can be a sensitive marker for detection of cardiotoxicity in dogs treated with doxorubicin. PMID- 29786173 TI - Cryopreservation of stallion semen: laboratory assessment of sperm injuries after cushioned centrifugation and freezing with conventional and alternative directional freezing methods. AB - Fresh 36 ejaculates of 13 stallions were split into two volumes, centrifuged with and without cushion and frozen with Conventional and two prototype, Drum and Directional, methods using 0.5 ml straws for the Conventional and Drum, and 2 ml flat straws for both the Drum and Directional. Cushioned centrifugation increased total motility (61.2 +/- 18.6% vs. 57.5 +/- 18.6%; P < 0.001) and mean velocity (84.3 +/- 15.6% vs. 83.2 +/- 13.8%; P < 0.05) when compared to not cushioned centrifugation, estimated after cooling the sperm at 40C for 90 min before freezing. Cushioned centrifugation also increased (P < 0.001) spermatozoa with polarized mitochondrial membranes (46.8 +/- 11.4% vs. 43.4 +/- 10.6%) and intact plasmatic/acrosomal membranes (41.0 +/- 11.2% vs. 38.5 +/- 11.3%) of frozen/thawed sperm, with respect to not cushioned centrifugation. However, no effects of the centrifugation were evidenced for classical kinetic parameters. Flat straws had negative effect for almost all the parameters analyzed at thawing (T,) and after 3 hours' incubation at 370C (T1), while the Drum method with Paillettes did not show appreciable affects. The variability among stallions was relevant (5% to 69% variance for kinetics and membrane status), while the variability among ejaculates was minor (9% to 28%). Factorial analysis identified three relevant, factors with different informational content: Factor 1 represented by membranes status, Factor 2 by kinetics estimated at T0, and Factor 3 by kinetics estimated at T1. Cushioned centrifugation had some beneficial effects for the membrane status of the frozen/thawed sperm, while the use of flat straws needs to be improved. PMID- 29786174 TI - Effect of beta-hydroxy-beta-methylbutyrate acid on meat performance traits and selected indicators of humoral immunity in goats. AB - The aim of this study was to determine the effect of beta-hydroxy-beta methylbutyrate acid, on parameters of meat performance in goats as well as on selected parameters of non-specific humoral defense. An experiment was performed on 24 Alpine kids divided into two equal groups: I - control and II - experimental. Over a period of 60 days, the animals were fed an HMB-supplemented diet. The following meat performance parameters were determined: body weight, daily gains, growth rate, the dimensions of musculus longissimus dorsi (m.l.d.) sections and fat thickness over the loin "eye". Selected indicators of non specific humoral immunity were determined in the blood serum of kids: lysozyme activity, ceruloplasmin activity and gamma globulin content. It was found that the kids administered HMB had a significantly higher body weight on days 30 and 60 of the experiment compared to the control group. The kids in this group also had a significantly more favorable musculature development. Simultaneously, a significant impact of HIMB on the examined immunological indices was found. The significance of differences in relation to the control group was confirmed statistically for lysozyme activity and ceruloplasmin activity on days 30 and 60, while the content of gammaglobulins was confirmed statistically on days 15, 30 and 60 of the study. It was also found that the addition of HMB had a stimulating impact on immunity and growth rate as well as on the development of muscles. It is thus justified to administer HMB to early-weaned kids to enhance their rearing parameters. PMID- 29786175 TI - Regulation of p16 gene expression by histone H3 acetylation in canine lymphoid tumor cell lines. AB - In order to investigate whether suppression of the p16 gene is mediated by histone H3 acetylation in 4 canine lymphoid tumor cell lines, the gene's acetylation status was examined. In 2 canine lymphoid tumor cell lines with low p16 mRNA expression (GL-1 and UL-1), the acetylation level was lower than that in CL-1 cells with high p16 mRNA expression. The expression of the p16 gene in these 2 cell lines was markedly restored after culture in the presence of a histone deacetylase inhibitors trichostatin A, indicating that p16 was inactivated by hypoacetylation. Findings obtained this study will add new insights and lead to the better understanding of the disease pathogenesis and future development of epigenetic therapeutic strategies. PMID- 29786176 TI - Does the routine handling affect the phenotype of disease model mice? AB - The three different mouse handling methods, picking up by tails, tunnels, and open hands were performed using the ICGN glomerulonephritis mouse and the severity of symptoms was evaluated. The handling groups exhibited a tendency of more severe symptoms than the non-handling control group. Female mice handled by their tails showed significantly more severe symptoms than the control group. In addition, we subjected the normal laboratory mice, C57BL/6 and BALB/c mice to tail and tunnel handling to assess the stress conditions. The plasma corticosterone level in the tail-handled mice was higher than that in control mice. These results indicate that handling causes stress and may affect the phenotype of disease model mice. PMID- 29786179 TI - [Update 2017 of the KDIGO guidelines on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). What are the real changes?] AB - Guidelines for the assessment, diagnosis and therapy of the alterations that characterize the CKD-MBD are an important support in the clinical practice of the nephrologist. Compared to the KDIGO guidelines published in 2009, the 2017 update made changes on some topics on which there was previously no strong evidence both in terms of diagnosis and therapy. The recommendations include the diagnosis of bone anomalies in CKD-MBD and the treatment of mineral metabolism abnormalities with particular regard to hyperphosphataemia, calcium levels, secondary hyperparathyroidism and anti-resorptive therapies. The Italian Study Group on Mineral Metabolism, in reviewing the 2017 recommendations, aimed to assess the weight of the evidence that led to this update. In fact, on some topics there has not been a substantial difference on the degree of evidence compared to the previous guidelines. The Italian Study Group emphasizes the points that may still reserve critical issues, including interpretation, and invites an evaluation that is articulated and personalized for each patient. PMID- 29786178 TI - Using Nassarius stolatus as a potential heavy metal biomonitor. AB - Nassarius stolatus was evaluated as the potential heavy metal (Cd, Fe, Mn, Ni and Pb) accumulator in Don Hoi Lot sandbar, Samut Songkhram province, Thailand. This selected species belongs to the Gastropoda, which is widely distributed in the coastal areas from the upper Gulf through the southern part of Thailand. From our findings, the heavy metal accumulations in N. stolatus tissues were Fe > Pb > Mn > Ni > Cd. The retrieved bioaccumulation factor (BAF) indicated that N. Stolatus has high potential to be a biomonitor for the contaminations of Fe and Mn in water and Cd, Ni and Pb in sediment. PMID- 29786177 TI - Usefulness of an anesthetic mixture of medetomidine, midazolam, and butorphanol in cotton rats (Sigmodn hispidus). AB - Tne cotton rat (Sigmodon hispidus) is a laboratory rodent used for studying human infectious diseases. However, a lack of suitable anesthetic agents inconveniences the use of cotton rats in surgical manipulation. This study demonstrated that subcutaneous injection of the mixture of medetomidine, midazolam, and butorphanol (0.15, 2.0, and 2.5 mg/kg, respectively), which is a suitable anesthetic agents for mice and rats, produced an anesthetic duration of more than 50 min in cotton rats. We also demonstrated that 0.15 mg/kg of atipamezole, an antagonist of medetomidine, produced a quick recovery from anesthesia in cotton rats. This indicated that the anesthetic mixture of medetomidine, midazolam, and butorphanol, functioned as a useful and effective anesthetic for short-term surgery in cotton rats. PMID- 29786180 TI - [Bartter syndrome, severe rare orphan kidney disease: a step towards therapy through pharmacogenetic and epidemiological studies]. AB - Bartter syndromes (BS) types 1-5 are rare salt-losing tubulopathies presenting with overlapping clinical phenotypes including marked salt wasting and hypokalemia leading to polyuria, polydipsia, volume contraction, muscle weakness and growth retardation. These diseases are due to an impairment of sodium, potassium, chloride reabsorption caused by mutations in genes encoding for ion channel or transporters expressed in specific nephron tubule segments. Particularly, BS type 3 is a clinically heterogeneous form caused by mutations in CLCNKB gene which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. Specific therapy for BS is lacking and the only pharmacotherapy up today available is purely symptomatic and characterized by limiting side effects. The improvement of our understanding of the phenotype/genotype correlation and of the precise pathogenic mechanisms associated with BS type 3 as well as the pharmacological characterization of ClC K chloride channels are fundamental to design therapies tailored upon patients' mutation. This mini review focused on recent studies representing relevant forward steps in the field as well as noteworthy examples of how basic and clinical research can cooperate to gain insight into the pathophysiology of this renal channelopathy, paving the way for a personalized therapy. PMID- 29786181 TI - [New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of Nephrologists form Lombardy]. AB - Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago. PMID- 29786183 TI - [Hyperkalemia as a limiting factor in the use of drugs that block the Renin Angiotensin Aldosterone System (RAAS)]. AB - Angiotensin-converting enzyme (ACE-I) inhibitors and ARBs have shown real efficacy in reducing blood pressure, proteinuria, in slowing the progression of chronic kidney disease (MRC) and in clinical improvement. in patients with heart failure, diabetes mellitus and ischemic heart disease. However, their use is limited by some side effects such as the increase in serum potassium (K), which can be particularly severe in patients with renal insufficiency. In the 23,000 patients followed by the PIRP project of the Emilia-Romagna Region, hyperkalaemia at the first visit (K> 5.5 mEq / L) was present in about 7% of all patients. The prevalence of K values> 5.5 mEq / L increased in relation to the CKD stage, reaching 11% in patients in stage 4 and 5. Among patients with values of K> 5.5 at baseline, 44.8% were in therapy with ACE-I / ARB inhibitors, 3.8% with anti mineralcortoid and a further 3.9% concurrently taking SRAA-blocking agents and K sparing diuretics. Counter-measures to avoid the onset of hyperkalemia during treatment with drugs that block the RAAS range from the low-K diet, to diuretics and finally to drugs that promote fecal elimination of K. Among these, polystyrene sulfonates, which have more than 50 years of life, exchange K with sodium or calcium. These drugs, however, in chronic use, can lead to sodium or calcium overload and cause dangerous intestinal necrosis. Recently two new highly promising drugs have been introduced on the market for the treatment of hyperkalemia, the patiromer and sodium zirconium cyclosilicate. The patiromer, which is a potassium-calcium exchanger, acts at the level of the colon where there is a higher concentration of K and where the drug is most ionized. Sodium zirconium cyclosilicate (ZS-9) is a resin with micropores of well-defined dimensions, placed in the crystalline structure of the zirconium silicate. The trapped K is exchanged with other protons and sodium. However, even these drugs will have to demonstrate their long-term efficacy and safety to be considered true partners of RAAS blockers in some categories of patients. PMID- 29786182 TI - [Medicine and Nephrology from Social Networks]. PMID- 29786184 TI - [Protein carbamylation: what it is and why it concerns nephrologists]. AB - Spontaneous urea dissociation in water solution is a prominent source of protein carbamylation in our body. Protein carbamylation is a well-known phenomenon since early seventies. Some years ago, much interest in the diagnostic power of carbamylated protein arouse. Recently the target of the researches focused on its potential cardiovascular pathogenicity. Some authors claimed that this could be a reason for higher cardiovascular mortality in uremic patients. Nutritional therapy, amino acids supplementation and intensive dialysis regimen are some of the therapeutic tools tested to lower the carbamylation burst in this population. PMID- 29786185 TI - [An unusual presentation of Amyloidosis AL]. AB - We describe the case of a 74-year-old man admitted to our Nephrology Unit with nephrotic syndrome and mild kidney disease. A complete panel of laboratoristic and instrumental tests did not provide useful information for diagnosis. No specific signs or symptoms suggested the presence of AL amyloidosis. As a matter of fact, diagnosis was reached thanks to the hystopathologic examination of renal tissue and bone marrow, since the associated B-cell lymphoproliferative disorder had not revealed itself through serum and urine electrophoresis and immunofixation. This recent case provides the opportunity to review about the disease and to revaluate the renal biopsy as a first line exam in a clinical context where laboratoristic and instrumental tests offer us poor information. PMID- 29786186 TI - [EBV-ASSOCIATED PNEUMONIA IN PATIENT WITH GRANULOMATOSIS WITH POLYANGIITIS (GPA) IN IMMUNOSOPPRESSIVE THERAPY TREATED WITH ACICLOVIR]. AB - Granulomatosis polyangiitis (GPA) is an ANCA-related vasculitis (AAV) whose clinical manifestations mainly concern the respiratory tract (upper and lower) and the kidney. The treatment of GPA (as well as other AAV) includes the use of immunosuppressive drugs with numerous side effects; the most frequent complications are infectious and neoplastic. GPA frequently relapses. Epstein Barr Virus (EBV) is a ubiquitous virus; it is estimated that about 90% of the world's population has BEEN EXPOSED TO with this pathogen and has subsequently developed a latent infection. Under certain conditions including immunosuppression EBV may reactivate. We report the clinical case of a 67-year old woman who presented with GPA involving the upper respiratory tract and renal failure with the need for hemodialysis treatment. The fourth month of induction therapy with cyclophosphamide and methylprednisone she presented with dyspnea and respiratory failure. After excluding pulmonary embolism and heart failure, a series of investigations including high resolution tomography and fibroscopy with broncoalveolar lavage (BAL) were performed which excluded recurrence of pulmonary vasculitis including alveolar haemorrhage A BAL demonstrated EBV-DNA. On this basis EBV pneumonia was diagnosed, and antiviral therapy with acyclovir was begun, followed by clinical and radiological improvement. In patients with GPA treated with immunosuppressive drugs pulmonary involvement may not only be due to the underlying vasculitis, but also to opportunistic agents, which must always be considered. PMID- 29786187 TI - [Steroid-resistant focal segmental glomerulosclerosis treated with cascade plasmafiltration and rituximab]. AB - A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m2) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS. Clinical trials should be carried out for protocol approval. PMID- 29786188 TI - [A young girl with recurrent calculosis and hypercalcemia]. AB - Mutations of the CYP24A1 gene are associated with alterations in the activity of the enzyme 25-OH-D-24-hydroxylase, resulting in dysfunction of the metabolism of vitamin D. This enzymatic deficiency may cause hypercalcemia, low parathyroid hormone levels, hypercalciuria, nephrolithiasis and nephrocalcinosis. The clinical case of a young woman with recurrent renal lithiasis, hypercalcemia and hypercalciuria is described. These features are linked to deficiency of the enzyme 25-OH-D-24-hydroxylase, therefore to a biallelic mutation of the CYP24A1 gene. PMID- 29786189 TI - [Renal Infarction: multicentric cases in Piedmont]. AB - : We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57+/-16i; 23 F age 70+/-18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (>530 UI/ml) in 96% of cases (45 cases out of 47), PCR (>0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR <60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76+/-12 years) vs group 2 (54+/-17 years) and group 3 (56+/-17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate. CONCLUSIONS: Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy. PMID- 29786190 TI - [Identification of a new mutation of the NPHP1 gene]. AB - Kidney cystic diseases are inherited disorders causing chronic renal failure. According to the genetic defect they are classified as diseases of the primary ciliary complex and uromodulin-associated diseases. Mutations in genes coding for ciliary proteins are the basis of a broad category of genetic diseases, called ciliopathies. To date, three important ciliopathies are known: the autosomal dominant form and the recessive shape of the polycystic kidney and the nephronophthisis (NPHP). Juvenile Nephronophthisis (NPHP) is a progressive renal tubulo-interstitial disorder with a form of autosomal recessive inheritance that progresses inexorably towards terminal renal failure. Three different forms have been distinguished: juvenile (NPH1), infantile (NPH2) and adolescent (NPH3). Juvenile Nephronophthisis or nephronophthisis type 1 (NPH1), is the most frequent form. In most patients with a suspected diagnosis of NPHP, based primarily on clinical and radiological data, the deletion in homozygous NPHP1 is present in 20 40% of cases. Heterozygous deletions are found in 6% of patients, with concomitant mutation of the NPHP1 gene on the second allele. In this study we subjected to genetic screening 6 patients with suspected NPHP causing chronic renal failure, belonging to 6 families. The genetic screening identified in 2/6 patients a deletion of exons 5-7-20 and in 4/6 patients an heterozygous deletion of exon 20 and an heterozygous deletion on exon 17 not yet described in literature. Our results suggest that genetic screening should be included in the diagnostic procedure of patients with suspected nephronophthisis and that it may be used alternatively to renal biopsy. PMID- 29786191 TI - [Waiting for General Data Protection Regulation]. PMID- 29786193 TI - ? PMID- 29786192 TI - ? PMID- 29786194 TI - [CLINICAL RESEARCH OF INDIVIDUAL PERCUTANEOUS CANNULATED SCREWS FIXATION FOR TREATMENT OF Herbert TYPE Ib SCAPHOID FRACTURE]. AB - OBJECTIVE: To investigate the effectiveness of individual percutaneous cannulated screws fixation of computer-assisted design combined with three-dimensional (3D) guide plate by comparing with cast immobilization and open internal fixation for treatment of Herbert type Ib scaphoid fracture. METHODS: Between January 2010 and June 2015, 56 patients with fresh Herbert type Ib scaphoid fracture were treated with cast immobilization in 16 cases (external fixation group), with open reduction and internal fixation in 20 cases (open reduction group), and with individual percutaneous cannulated screws fixation of computer-assisted design combined 3D guide plate in 20 cases (minimal invasion group). There was no significant difference in gender, age, injury cause, side, disease duration, and classification of fractures between groups P>0.05).The time of bone union, bone nonunion rate, return-to-work time, wrist range of motion (ROM), and Mayo function score were recorded and compared. RESULTS: Primary healing of incision was obtained in open reduction group and minimally invasion group, without related complications. The cases were followed up 10-24 months (mean, 16.6 months). The time of bone union and return-to-work time of minimal invasion group were significantly shorter than those of the other 2 groups (P<0.05), and the rate of bone nonunion was significantly lower than that of the other 2 groups (P<0.05). At last follow-up, the wrist ROM of minimal invasion group[(104.40+/ 3.46) degrees ] was significantly larger than that of external group[(94.20+/ 2.42) degrees ] and open reduction group[(96.40+/-2.66) degrees ] (P<0.05). According to Mayo function score, the results were excellent in 6 cases, good in 5 cases, fair in 2 cases, and poor in 3 cases in external fixation group, with an excellent and good rate of 69%; the results were excellent in 9 cases, good in 7 cases, fair in 2 cases, and poor in 2 cases in open reduction group, with an excellent and good rate of 80%; the results were excellent in 16 cases, good in 3 cases, and fair in1 case in minimal invasion group, with an excellent and good rate of 95%; there was significant difference in excellent and good rate among groups (P<0.05). CONCLUSIONS: Individual percutaneous cannulated screws fixation of computer-assisted design combined with 3D guide plate has satisfactory effectiveness in the treatment of Herbert type Ib scaphoid fractures, with the advantages of mini-invasion, high accuracy, high rate of bone union, less complication, early return-to-work time. PMID- 29786196 TI - [IMAGING STUDY ON DESIGN AND GEOMETRIC MATCH OF A NEW TYPE OF SHORT FEMORAL INTERTROCHANTERIC NAIL WITH ANTERIOR CURVATURE]. AB - OBJECTIVE: To design a new type of short femoral intertrochanteric nail (FITN) with anterior curvature (19.5 cm in length and 120 cm in radius) and observe the geometric match with medullary cavity of the femur. METHODS: Between November 2015 and June 2016, 25 geriatric patients with femoral intertrochanteric fractures were treated with the newly designed FITN. There were 7 males and 18 females with an average age of 82.3 years (range, 65-94 years). According to AO/OTA fracture classification, 3 cases were rated as A1.2, 2 cases as A1.3, 5 cases as A2.1, 8 cases as A2.2, and 7 cases as A2.3. The interval between injury and operation was 3.2 days (range, 2-7 days). Postoperatively, the nail entry point position (anterior, central, and posterior) on sagittal plane, the nail tip position (6-grade scale) and the nail tail level (3-grade scale) were measured using fluoroscopy and X-ray films to evaluate the geometric match of the nail with medullary cavity of the femur. RESULTS: One patient with Parkinson disease died of asphyxia and pulmonary infection. The other 24 patients were followed up 1-8 months (mean, 4 months). Fracture union time was 6-10 weeks (mean, 8 weeks). The mean Parker-Palmer mobility score was 5.5 (range, 4-8). No patient had hip thigh pain. The nail entry point was positioned anterior in 2 cases (8%), central in 18 cases (72%), and posterior in 5 cases (20%). The distal nail tip located at the central canal axis (grade 0) in 15 cases (60%), at anterior without contact with the anterior inner cortex (grade 1) in 8 cases (32%), at posterior (grade 1) in 1 case (4%), and at anterior with slight nail-tip impingement with the anterior cortex (grade 2) in 1 case (4%). The proximal nail tail level did not protrude out beyond the greater trochanter (grade 0) in 13 cases (52%), protruded out less than 5 mm (grade 1) in 9 cases (36%), and more than 5 mm (grade 2) in 3 cases (12%). CONCLUSIONS: The newly designed FITN has a good geometric match with the femur medullary canal in Chinese population, which may reduce the nail related complications. PMID- 29786195 TI - [EFFECTIVENESS OF PROXIMAL HUMERAL INTERNAL LOCKING SYSTEM PLATE FOR PROXIMAL HUMERUS FRACTURES]. AB - OBJECTIVE: To analyze the effectiveness of proximal humeral internal locking system (Philos) plate for proximal humerus fracture. METHODS: Thirty-three patients with proximal humerus fracture were treated with open reduction and internal fixation with Philos plate between January 2009 and January 2014. There were 19 males and 14 females, aged 23-89 years (mean, 56.6 years). The left side was involved in 15 cases, and the right side in 18 cases. The injury causes included falling in 20 cases and traffic accident in 13 cases. All cases received X-ray and CT scan and three-dimensional reconstruction before operation. According to the Neer classification, 8 cases were rated as two-part fractures, 15 cases as three-part fractures, and 10 cases as four-part fractures. The interval time between injury and surgery was 1-7 days (mean, 3.67 days). Postoperative functional outcome was evaluated using the Constant-Murley score. RESULTS: Infection and liquefaction occurred in 2 cases respectively, which was cured after corresponding treatment; primary healing of wound was obtained in the other 29 cases. Five patients had shoulder pain. The patients were followed up 11 47 months (mean, 33 months). The mean time of fracture union was 7.5 months (range, 5-9 months) on the X-ray films. Humeral head necrosis occurred in 2 patients with Neer four-part fractures, and internal fixation failure occurred in 3 patients (2 screw broken and 1 plate broken) with four-part fractures (2 cases) and three-part fractures (1 case), which was cured after conservative treatment. At last follow-up, the mean Constant-Murley score was 70.5 (range, 42-90); the results were excellent in 3 cases, good in 21 cases, moderate in 6 cases, and poor in 3 cases. CONCLUSIONS: Satisfactory results can be expected for proximal humeral fracture by using of the proximal humeral internal locking system plate based on strict indication and early rehabilitation training. PMID- 29786197 TI - [ARTHROSCOPICALLY ASSISTED TREATMENT OF POSTERIOR CRUCIATE LIGAMENT AVULSION FRACTURE WITH MENISCUS POSTERIOR HORN TEAR]. AB - OBJECTIVE: To evaluate the effectiveness of arthroscopically assisted treatment of posterior cruciate ligament (PCL) tibial eminence avulsion fractures associated with meniscus posterior horn tear. METHODS: Between January 2012 and December 2014, 21 patients with PCL avulsion fracture and meniscus posterior horn tear were arthroscopically treated with polyester suture and hollow screw fixation. There were 10 males (10 knees) and 11 females (11 knees), aged 14-53 years (mean, 35.7 years). The causes included sport injury in 11 cases, traffic accident injury in 9 cases, and daily life injury in 1 case. Based on the anteroposterior and lateral X-ray films, CT, and MRI, PCL avulsion fractures were diagnosed, and 2 cases had anterior cruciate ligament avulsion fractures. The results of posterior drawer test were positive in all patients, with no end point in 14 cases and with soft end point in 7 cases; all patients showed tibial sink. The preoperative International Knee Documentation Committee (IKDC) score and Lysholm score were 46.5+/-5.5 and 43.3+/-4.5 respectively. The time from injury to operation was 6-22 days (mean, 10 days). RESULTS: The operation time was 60 100 minutes (mean, 75 minutes). Primary healing of incision was obtained in all patients, without no complication of infection. The mean follow-up time was 27.4 months (range, 12-46 months). The results of posterior drawer test were negative in 19 cases, and positive in 2 cases (having hard end point). Tibial sink disappeared. At last follow-up, X-ray film showed good healing of fracture, and no displacement. The patients had no locking knee, snapping or tenderness of joint space, and the Mcmurray sign was negative; the IKDC score and Lysholm score were significantly improved to 92.0+/-2.5 and 92.7+/-2.6 respectively (t=-39.903, P=0.000; t=-43.242, P=0.000). The range of motion was normal in 20 patients (0 130 degrees ) except 1 patient having limited flexion (0-80 degrees ), whose range of motion returned to 0-120 degrees after release. CONCLUSIONS: The arthroscopic fixation technique has satisfactory results for the reduction and fixation of PCL avulsion fracture associated with meniscus posterior horn tear because of easy operation, firm fixation, and economic price. PMID- 29786198 TI - [EFFECTIVENESS OF SPRING HOOK PLATE FOR POSTERIOR MALLEOLUS FRACTURE]. AB - OBJECTIVE: To investigate the effectiveness of spring hook plate for posterior malleolus fracture by comparing with cannulated screw. METHODS: Between March 2012 and September 2013, 100 cases of posterior malleolus fracture were treated. Fracture was fixed with spring hook plate in 50 cases (research group) or with cannulated screw in 50 cases (control group). There was no significant difference in gender, age, cause of injury, associated injury, and injury to operation time between 2 groups P>0.05). The operation time, intraoperative blood loss, union time of fracture, ankle range of motion (ROM), and complications were recorded and compared. The ankle joint function was evaluated by the ankle hindfoot scale of American Orthopedic Foot and Ankle Society (AOFAS). RESULTS: There was no significant difference in operation time and intraoperative blood loss between 2 groups P>0.05). The patients were followed up 6-12 months (mean, 9.8 months) in the control group and 6-12 months (mean, 9.2 months) in the research group. The X ray films showed that fracture union was achieved in 2 groups; the union time of the research group[(9.5+/-1.4) weeks] was significantly shorter than that of the control group[(10.5+/-1.3) weeks] (t=2.029, P=0.017). The ROM was (25.1+/-3.2) degrees for dorsal extension and was (45.3+/-2.3) degrees for plantar flexion in the research group at 6 months after operation, which were significantly better than those of the control group[(22.2+/-2.3) degrees and (41.2+/-2.5) degrees ] (t=-3.950, P=0.001; t=-5.212, P=0.000). The ankle hindfoot scale of AOFAS was 85.1+/-8.6 in the control group at 6 months; the results were excellent in 15 cases, good in 20 cases, and moderate in 15 cases with an excellent and good rate of 70%. The ankle hindfoot scale of AOFAS was 89.4+/-7.9 in the research group; the results were excellent in 20 cases, good in 22 cases, and moderate in 8 cases with an excellent and good rate of 84%; there was significant difference between 2 groups (t=-2.191, P=0.042; chi2=0.413, P=0.018). Incision infection occurred in 3 cases of the control group and in 2 cases of the research group, which was cured after dressing change; screw loosening and fracture displacement occurred in 3 and 4 cases of the control group, but did not in the research group. The complication rate of the control group and the research group was 20% and 4% respectively, showing significant difference between 2 groups (chi2=6.061, P=0.028). CONCLUSIONS: Spring hook plate can shorten the time of union, increase the ROM of the ankle after operation, get good functional restoration, and decrease the rate of complication compared with cannulated screw fixation. PMID- 29786199 TI - [DESIGN AND BIOMECHANICAL STUDY OF TRANSARTICULAR CUBOID BONE PLATE]. AB - OBJECTIVE: To design a new type of transarticular cuboid bone plate by measuring and collecting the anatomic data of the articular surface around cuboid, and to carry out comparative biomechanical study. METHODS: The angle alpha (between the fifth metatarsocuboid joint and the fifth metatarsal bone) and the angle beta (between the fifth metatarsocuboid joint and the calcaneocuboid joint) were measured in 100 adults on medial oblique X-ray film and 30 adult foot specimens. Based on literature data, the transarticular cuboid bone plate was designed with an angle alpha of 70 degrees and an angle beta of 30 degrees . Six adult cadaver feet were chosen and were transected approximately 15 cm proximal to the ankle. Five strain gauges were placed at the calcaneus, cuboid, and the fourth and fifth metatarsal bones. The vertical pressure was loaded on the foot at 0-600 N, the strain value was measured. Then the cuboid fracture model was established and 600 N load was given on foot to measure the strain value and compare with the strain value before fracture. The specimens were randomly divided into groups A and B (n=3). Fracture was fixed with transarticular cuboid bone plate and 9 screws in group A and with double plate and 8 screws in group B, then the 600 N load was given to measure the strain value and vertical displacement of the fracture fragments. RESULTS: After loads of 0-600 N on the foot, the strain value of the 5 points showed an increased trend. No significant difference was found in the strain value between pre- and post-fracture at a, d, and e points P>0.05), but it was significantly larger at post-fracture than pre-fracture at b and c points (P<0.05). After fracture fixation, no significant difference was shown in the strain value at 5 points between groups A and B when loads of 0-600 N was given P>0.05). The experimental data showed that the strain value change mainly focused on the fracture site under the same load, so the strain value after fracture fixation was similar to that before fracture at b and c points P>0.05). The vertical displacement values of medial and lateral fracture fragments in group A[(0.804+/-0.011) mm and (0.672+/-0.036) mm] were significantly less than those in group B[(1.126+/-0.083) mm and (1.007+/-1.103) mm] (t=-6.711, P=0.003; t= 5.307, P=0.006). CONCLUSIONS: Through biomechanical study, a new type of transarticular cuboid bone plate has better fixation effect. PMID- 29786200 TI - [COMPARISON OF TWO ANIMAL MODELS WITH CARTILAGE DEFECT]. AB - OBJECTIVE: To compare difference in the establishment of animal model of cartilage defect by resection of medial collateral ligament and meniscus and by cartilage excavation so as to provide a proper way for the choose of animal model preparation of catilage defect. METHODS: Ten healthy beagles, male or female, weighing 5.0-10.0 kg, were randomly divided into 3 groups. Resection of knee collateral ligament and meniscus was performed on 4 beagles of group A, cartilage excavation of knee-joints in 4 beagles of group B, and no treatment on 2 beagles of group C as controls. At 16 weeks after modeling, MRI, gross observation, HE staining, Safranin O staining, and toluidine blue staining were performed, and Osteoarthritis Research Society International (OARSI) score was recorded. RESULTS: MRI and histology observation showed no obvious cartilage defect in group A; obvious cartilage defects were observed in group B and gross observation showed dramatic dark red cartilage defects. OARSI score was significantly lower in group A (0.940+/-0.574) than group B (4.500+/-0.516) (t=18.461, P=0.000). CONCLUSIONS: The cartilage excavation is better than resection of both meniscus and medial collateral ligament, which provides a good method of establishing an animal model of cartilage defect at 16 weeks after operation. PMID- 29786201 TI - [CHANGES OF SEMAPHORIN 3A EXPRESSION IN HEALING OF TIBIA FRACTURE AFTER TRAUMATIC BRAIN INJURY]. AB - OBJECTIVE: To investigate the mechanism of Semaphorin 3A (Sema3A) in fracture healing after nerve injury by observing the expression of Sema3A in the tibia fracture healing after traumatic brain injury (TBI). METHODS: A total of 192 Wistar female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into tibia fracture group (group A, n=48), TBI group (group B, n=48), TBI with tibia fracture group (group C, n=48), and control group (group D, n=48). The tibia fracture model was established at the right side of group A; TBI model was made in group B by the improved Feeney method; the TBI and tibia fracture model was made in group C; no treatment was given in group D. The tissue samples were respectively collected at 3, 5, 7, 14, 21, and 28 days after operation; HE staining, immunohistochemistry staining, and Western blot method were used for the location and quantitative detection of Sema3A in callus tissue. RESULTS: HE staining showed that no obvious changes were observed at each time point in groups B and D. At 3 and 5 days, there was no obvious callus growth at fracture site with inflammatory cells and fibrous tissue filling in groups A and C. At 7 and 14 days, fibrous tissue grew from periosteum to fracture site in groups A and C; the proliferation of chondrocytes in exterior periosteum gradually formed osteoid callus at fracture site in groups A and C. The chondrocyte had bigger size, looser arrangement, and more osteoid in group C than group A. Group B had disorder periosteum, slight subperiosteal bone hyperplasia, and no obvious change of bone trabecula in group B when compared with group D. At 21 and 28 days, cartilage callus was gradually replaced by new bone trabecula in groups A and C. Group C had loose arrange, disorder structure, and low density of bone trabecula, big callus area and few chondrocyte and osteoid when compared with group A; group B was similar to Group D. Immunohistochemistry staining showed that Sema3A expression in chondrocytes in group C was higher than that in group A, particularly at 7, 14, and 21 day. Sema3A was significantly higher in osteoblasts of new bone trabecula in group A than group C, especially at 14 and 21 days (P<0.05). Western blot results showed that the Sema3A had the same expression trend during fracture healing in groups A and C. However, the expression of Sema3A protein was significantly higher in group C than group A (P<0.05) and in group B than group D (P<0.05) at 7, 14, 21, and 28 days. CONCLUSIONS: Abnormal expression of Sema3A may play a role in fracture healing after nerve injury by promoting the chondrocytes proliferation and reducing the distribution of sensory nerve fibers and osteoblast differentiation. PMID- 29786202 TI - [EXPRESSION OF HUMAN TRANSFORMING GROWTH FACTOR beta1 GENE MEDIATED BY ADENOVIRUS IN HAMSTRING TENDON AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION IN RABBITS]. AB - OBJECTIVE: To detect the expression of human transforming growth factor beta1 (hTGF-beta1) gene mediated by adenovirus (Ad) in hamstring tendon after anterior cruciate ligament (ACL) reconstruction in rabbits. METHODS: Ad-hTGF-beta1 and Ad green fluorescent protein (GFP) were diluted to 5*108 PFU/mL with DMEM. Forty eight New Zealand white rabbits were divided into 3 groups randomly (n=16) for ACL reconstruction with hamstring tendon autograft. Hamstring tendon was cultured and transfected with Ad-hTGF-beta1 (group A) and Ad-GFP (group B) for 12 hours before ACL reconstruction, and was cultured with DMEM in group C. After 12 hours of transfection, green fluorescence was observed in groups A and B under fluorescence microscopy. At 2, 4, 6, and 8 weeks after operation, the hamstring tendon was harvested to detect the mRNA and protein expressions of hTGF-beta1 by real time fluorescence quantitative PCR and Western blot. RESULTS: Green fluorescence was observed after 12 hours of transfection in groups A and B. TGF beta1 protein level reached (221.0+/-12.2) ng/mL at 12 hours in group A. The hTGF beta1 mRNA expression could be detected in group A, but it could not be detected in group B and group C. The mRNA expression levels of hTGF-beta1 were 1.004+/ 0.072 at 2 weeks, 0.785+/-0.038 at 4 weeks, 0.469+/-0.053 at 6 weeks, and 0.172+/ 0.021 at 8 weeks in group A, showing significant difference (P<0.05). Western blot results showed weakly positive band in groups B and C; the protein expression of TGF-beta1 in group A was significantly higher than that in groups B and C (P<0.05), but no significant difference was found between groups B and C P>0.05). The protein expression of TGF-beta1 gradually reduced with time, showing significant difference between different time points (P<0.05). CONCLUSIONS: Ad hTGF-beta1 can transfect the hamstring tendon successfully, and it can effectively express for a long time after ACL reconstruction. PMID- 29786203 TI - [ROLES OF SIGNAL MOLECULE p38 INVOLVED IN MINERALIZATION AND MATURATION OF OSTEOBLASTS PROMOTED BY LOW FREQUENCY PULSED ELECTROMAGNETIC FIELDS]. AB - OBJECTIVE: To investigate whether signal molecule mitogen-activated protein kinases (MAPKs) involves in the process of the mineralization and maturation of rat calvarial osteoblasts promoted by 50 Hz, 0.6 mT pulsed electromagnetic fields. METHODS: Rat calvarial osteoblasts were obtained by enzyme digestion from the skull of 6 neonatal Wistar rats of SPF level. The primary osteoblasts were treated in 50 Hz and 0.6 mT pulsed electromagnetic fields for 0, 5, 10, 20, 40, 60, and 120 minutes; the protein expression of phosphorylated MAPKs was detected by Western blot. The osteoblasts were randomly divided into group A (control group), group B (low frequency pulse electromagnetic fields treatment group), group C (SB202190 group), and group D (SB202190+low frequency pulse electromagnetic fields treatment group); the alkaline phosphatase (ALP) activities were tested after corresponding treatment for 1, 4, and 7 days. The corresponding treated more than 90% confluenced osteoblasts were cultured under condition of osteogenic induction, then ALP staining and alizarin red staining were carried out at 9 and 12 days respectively. RESULTS: The results of Western blot showed that there was no significant changes in the protein expressions of phosphorylated level of extracellular signal-related kinases 1/2 and c-Jun amino N-terminal kinases 1/2 in 50 Hz, 0.6 mT pulsed electromagnetic fields P>0.05), but the phosphorylated level of p38 began to increase at 5 minutes, peaked at 40 minutes, then gradually decreased, and it was significantly higher at 5-120 minutes than at 0 minute (P<0.05). After the activities of p-p38 was inhibited by inhibitor SB202190, the ALP activities, positive colonies and area of ALP and calcified nodules of group B were significantly higher than groups A, C, and D (P<0.05). CONCLUSIONS: p38 is one of the signal molecules involved in the process of the mineralization and maturation of rat calvarial osteoblasts promoted by 50 Hz, 0.6 mT pulsed electromagnetic fields. PMID- 29786205 TI - [CLINICAL APPLICATION OF PEDICLED THORACOACROMIAL ARTERY PERFORATOR FLAP FOR PHARYNGOCUTANEOUS FISTULA REPAIR AFTER RADIOTHERAPY AND SALVAGE TOTAL LARYNGECTOMY]. AB - OBJECTIVE: To explore the effectiveness of pedicled thoracoacromial artery perforator (TAAP) flap for pharyngocutaneous fistula repair after total laryngectomy and radiotherapy. METHODS: Between February 2012 and January 2015, TAAP flap was used to repair pharyngocutaneous fistula after total laryngectomy and radiotherapy in 8 patients. The eight patients were male, aged from 46 to 72 years (mean, 51.8 years). The disease duration was 8-62 months (mean, 27.5 months). Fistula size ranged from 4.0 cm*2.5 cm to 6.0 cm*4.0 cm and the skin defect size ranged from 4.0 cm*3.0 cm to 6.0 cm*4.0 cm. The flap size ranged from 7.0 cm*4.0 cm*0.3 cm to 9.5 cm*6.0 cm*0.5 cm. The length of pedicle was (8.3+/ 0.5)mm. The distance from pivot point of flap to central point of recipient site was (94.5+/-1.9) mm. RESULTS: All 8 flaps survived and all incisions healed smoothly. The hospitalization time was 7-14 days (mean, 9.6 days). The barium meal examination showed no fistula or stenosis. The patients were followed up 8 42 months (mean, 28.5 months). During follow-up, the neck appearance was good, and no fistulas or stenosis occurred. Only linear scars were observed at the donor sites, pectoralis major muscle function was normal in all patients. CONCLUSIONS: Pharyngocutaneous fistula should be repaired as early as possible after total laryngectomy. TAAP flap is suitable for the reconstruction of pharyngocutaneous fistula after total laryngectomy. PMID- 29786204 TI - [STUDY ON MOLECULAR MECHANISM OF OSTEOCLAST DIFFERENTIATION INDUCED BY STAPHYLOCOCCAL PEPTIDOGLYCAN]. AB - OBJECTIVE: To investigate the molecular mechanism of osteoclast differentiation induced by Staphylococcal peptidoglycan (PGN-sa). METHODS: Raw264.7 cells were stimulated with PGN-sa and with PGN-sa+SC75741[a potent inhibitor of nuclear factor kappaB (NF-kappaB) activation] in a concentration of 200 ng/mL. The protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) was tested at 0, 1, 2, and 3 days; the proteins related to osteoclast differentiation of extracellular regulated protein kinases (ERK), p38, c-Jun N terminal kinase (JNK), NF-kappaB, inhibitor of NF-kappaB (IkappaB-alpha), Akt, and the phosphorylation forms of p38, ERK, JNK, Akt, NF-kappaB were measured at 0, 5, 10, 20, 40, and 60 minutes by Western blot. In addition, Raw264.7 cells were stimulated with PGN-sa in the concentrations of 100 ng/mL (group A), 200 ng/mL (group B), 400 ng/mL (group C), and with PBS (group D) for 1, 2, and 3 days; the expression levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), and IL-6 were detected by ELISA. RESULTS: The results of Western blot showed that the expression of NFATc1 increased gradually with time, showing significant difference between different time points (P<0.05). However, after SC75741 was added, the expression of NFATc1 was inhibited at 2 and 3 days, showing significant difference when compared with no addition of SC75741 (P<0.001). After stimulation of PGN-sa, the expression of IkB-alpha decreased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes. Meanwhile, the expression of p-NF-kappaB increased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes; and the expression of p-NF-kappaB at 5 minutes was significantly higher than that at 10 minutes (P<0.001). After the addition of SC75741, there was no change in the expressions of IkappaB-alpha and p-NF-kappaB, showing no significant difference between different time points P>0.05). Moreover, the expressions of ERK, p38, JNK, NF-kappaB, Akt, p-p38, p-ERK, p-JNK, and p-Akt showed no significant change between different time points P>0.05). ELISA results showed that there were no expressions of TNF-alpha and IL-1alpha in groups A-D at different time points. The expression of IL-6 had an increasing trend with time prolonged in each group, showing significant differences between different time points (P<0.05). Moreover, at 1 day after culture, the expression of IL-6 showed no significant difference among groups P>0.05). At 2 and 3 days after culture, the expression of IL-6 in groups A-C showed an increasing trend and was significantly higher than that in group D, showing significant difference among groups (P<0.05). CONCLUSIONS: PGN-sa can promote osteoclast differentiation through NF-kappaB signaling pathway, and IL-6 may play a role in this process. PMID- 29786206 TI - [PRIMARY STUDY ON CONTRALATERAL BREAST SYMMETRIZATION MAMMAPLASTY IN BREAST RECONSTRUCTION]. AB - OBJECTIVE: To explore the techniques and short-term effectivness of contralateral breast symmetrization mammaplasty in breast reconstruction. METHODS: Between February 2014 and December 2015, 11 patients received immediate or delayed breast reconstruction after nipple-sparing mastectomy (6 and 5 cases respectively) for contralateral breast symmetrization mammaplasty. The age ranged 36-55 years (mean, 45 years). The disease duration was from 7 days to 6 months (mean, 2.5 months) in 6 patients undergoing immediate breast reconstruction. According to tumor TNM staging, 2 cases were rated as TisN0M0, 3 cases as T1N0M0, and 1 case as T2N0M0. The duration was from 2 to 25 years (mean, 8 years) in 5 patients undergoing delayed breast reconstruction. The implant (7 cases) and latissimus dorsi (4 cases) were used for breast reconstruction; and breast augmentation (6 cases) and breast reduction (5 cases) were performed for contralateral breast symmetrization. RESULTS: One patient had local poor wound healing postoperatively and was cured; primary healing was obtained in the other patients, and no other postoperative complication of infection, implant exposure or capsular contracture was found. The patients were followed up 3 to 24 months (mean, 12 months). The reconstructive outcomes were excellent in 9 cases and good in 2 cases, with an excellent and good rate of 100%. There was no recurrence or metastasis. CONCLUSIONS: Simultaneous contralateral symmetrization with augmentation/reduction mammaplasty after breast reconstruction can obtain satisfactory symmetric outcomes. PMID- 29786207 TI - [RELATED FACTORS ANALYSIS OF DISTAL ADDING-ON PHENOMENON IN MAJOR THORACIC CURVE AFTER POSTERIOR SELECTIVE FUSION]. AB - OBJECTIVE: To identify the prevalence of distal adding-on phenomenon after posterior selective fusion in type Lenke 1A idiopathic scoliosis, to analyze its risk factors so as to find the reasonable choice for lowest instrumented vertebra (LIV). METHODS: A retrospective study was made on the clinical data of 43 patients with type Lenke 1A idiopathic scoliosis undergoing posterior selection fusion with pedicle screw instrumentation between July 2011 and December 2015. There were 15 males and 28 females, aged 12-18 years (mean, 16 years). The preoperative Cobb angle was (50.1+/-11.3) degrees . The anteroposterior and lateral radiographs were taken at preoperation, immediate after operation, and last follow-up to measure the radiographic parameters. Forty-three patients were divided into adding-on group and control group according to whether or not the occurrence of distal adding-on phenomenon on anteroposterior radiographs of the spine at last follow-up. All the factors that maybe cause distsal adding-on were evaluated by statistical analysis. RESULTS: The patients were followed up 12-50 months (mean, 26.5 months). At last follow-up, distal adding-on was observed in 10 of 43 patients (23.3%), including 2 males (13.3%) and 8 females (28.6%). Univariate analyses showed following several factors associated with adding on:preoperative lumbar flexibility, preoperative pelvic tilt in coronal plane, preoperative LIV+1 deviation from center sacral vertical line, L4 subtype, the difference between LIV and last touching vertebra (LTV) (LIV-LTV), the difference between LIV and lower end vertebra (LEV) (LIV-LEV), and the difference between LIV and stable vertebra (SV) (LIV-SV). The risk factors above were brought into Logistic regression model, the results showed that preoperative LIV+1 deviation (deviation>10 mm, odds ratio=10.812, P=0.026), LIV-LTV (LIV-LTV<1, odds ratio=9.017, P=0.04), and L4 subtype (1A-R, odds ratio=9.744, P=0.047) were significantly associated with adding-on. CONCLUSIONS: Preoperative LIV+1 deviation of >10 mm, L4 subtype (1A-R) and LIV-LTV of <1 are independent predictive factors of adding-on after surgery. As high risk of adding-on was closely related with the incorrect fusion level, it plays an important role for surgeons to decide the level of the fusion before surgery thoroughly. The LIV should be extended at least to LTV+1 to avoid adding-on phenomenon. PMID- 29786208 TI - [EFFECTS OF Tempol ON SURVIVAL OF RANDOM PATTERN SKIN FLAPS IN RATS]. AB - OBJECTIVE: To study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. METHODS: Eighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm*3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) after 1, 3, and 7 days. RESULTS: All of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-alpha, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-alpha, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). CONCLUSIONS: Tempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation. PMID- 29786209 TI - [EFFECTS OF CO-TRANSFECTION BY BONE MORPHOGENETIC PROTEIN 14 AND Noggin SHORT HAIRPIN RNA LENTIVIRAL VECTORS ON OSTEOGENIC DIFFERENTIATION OF ADIPOSE DERIVED STEM CELLS IN RATS]. AB - OBJECTIVE: To explore the effects on osteogenic differentiation of adipose derived stem cells (ADSCs) by simultaneously down-regulating Noggin combined with up-regulating bone morphogenetic protein 14 (BMP-14) in vitro. METHODS: Primary ADSCs were isolated and expanded in vitro from 5 Sprague Dawley rats (weighing, 250-300 g). ADSCs were transfected with lentiviral (Lv)-enhanced green fluorescent protein in group A (control group), with Lv-BMP-14 in group B, and with Lv-BMP-14 and Lv-Noggin shRNA in group C. BMP-14 and osteogenesis-related genes[collagen type I, alkaline phosphatase (ALP), and osteocalcin (OCN)] mRNA expression levels were detected by real time fluorescence quantitative PCR at 3, 7, and 14 days after transfection. Alizarin red staining for calcium nodules was also employed to assess the osteogenic ability of co-transfected ADSCs. RESULTS: At 3 days after transfection, no significant difference was found in BMP-14 mRNA expression among groups P>0.05). At 7 and 14 days after transfection, BMP-14 mRNA expression was significantly higher in group C than groups A and B, and in group B than group A (P<0.05). At 3 days after transfection, collagen type I, ALP, and OCN mRNA expressions of group C were significantly higher than those of groups A and B (P<0.05), but no significant difference was shown between groups A and B P>0.05). At 7 and 14 days, collagen type I, ALP, and OCN mRNA expressions were higher in group C than groups A and B, and in group B than group A, showing significant difference (P<0.05) except collagen type I mRNA expression at 7 days between groups A and B P>0.05). The results of alizarin red staining showed that the amount of calcium nodules presented an increased tendency in the order of group A, group B, and group C. CONCLUSIONS: BMP-14 is capable of enhancing osteogenic differentiation of ADSCs. A combination of inhibiting Noggin gene expression and enhancing BMP-14 gene expression in ADSCs can significantly strengthen osteogenic differentiation capability, showing significant synergistic effect. PMID- 29786210 TI - [ROLE OF FORKHEAD/FOX TRANSCRIPTION FACTOR 2 OVER-EXPRESSION IN REGULATING OSTEOGENIC DIFFERENTIATION OF BONE MARROW MESENCHYMAL STEM CELLS BY Wnt SIGNALING PATHWAYS]. AB - OBJECTIVE: To investigate the role of the forkhead/Fox transcription factor 2 (Foxc2) over-expression in regulating osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by Wnt-beta-catenin signaling pathways in vitro so as to provide the experimental basis for repairing osteonecrosis of the femoral head. METHODS: The recombinant lentivirus carrying green fluorescent protein (group A) or Foxc2 (group B) were used to transfect the fifth generation rabbit BMSCs, and untransfected BMSCs served as a control (group C). The cell viability was measured with water soluble tetrazolium-1 (WST-1) regent at 72 hours after transfection. After 2 weeks of transfection, the expression of beta-catenin in BMSCs was detected by real time fluorescence quantitative PCR, Western blot, and immunofluorescence staining. Meanwhile, the beta-catenin inhibitors XAV-939 (0, 0.1, and 1.0 MUmol/L) was added in group B; at 2 weeks after osteogenic and adipogenic induction, the gene and protein expressions of collagen type I (COL I), osteocalcin (OCN), and peroxisome proliferator activated receptor gamma 2 (PPARgamma-2) were detected by real time PCR and Western blot. RESULTS: WST-1 results showed that the cell viability of group B (130.85%+/-0.15%) was significantly higher than that of group A (100.45%+/-0.35%) (t=7.500, P=0.004) at 72 hours after transfection. At 2 weeks after transfection, the gene and protein expressions of beta-catenin in group B were significantly higher than those in group A (P<0.01). After XAV-939 was added in group B, the mRNA and protein expressions of OCN and COL I gradually decreased; the mRNA and protein expressions of PPARgamma-2 significantly increased (P<0.05), showing a dose dependent manner. CONCLUSIONS: The over-expression of Foxc2 gene in BMSCs may promote osteogenic differentiation by Wnt-beta-catenin signaling pathway. PMID- 29786211 TI - [EVALUATION OF AN OPTIMIZING PROTOCOL FOR FABRICATING A SCAFFOLD DERIVED FROM PORCINE SKELETAL MUSCLE EXTRACELLULAR MATRIX]. AB - OBJECTIVE: To explore an optimized protocol of decellularization to fabricate an ideal scaffold derived from porcine skeletal muscle acellular matrix. METHODS: Serial-step protocol of homogenating-milling-detergent method was used to fabricate decellularized porcine muscle tissue (DPMT) derived from native porcine skeletal muscle tissue from adult pig waist. Histological method was used to assess the effects of decellularization and degreasing. Sirius red staining was used to analyze collagen components. Scanning electron microscopy, BCA assay, and PicoGreen assay were used to evaluate the ultrastructure, total protein content, and DNA content in DPMT. The adipose derived stem cells (ADSCs), NIH3T3 cells, and human umbilical vein endothelial cells (HUVECs) were cultured in extraction liquor of DPMT in different concentrations for 1, 3, and 5 days, then the relative growth rate was calculated with cell counting kit 8 to assess the toxicity in vitro. Live/dead cell staining was used to evaluate the cytocompatibility by seeding HUVECs on the surface of DPMT and co-cultured in vitro for 3 days. For in vivo test, DPMT was subcutaneously implanted at dorsal site of male specific-pathogen free Sprague Dawley rats and harvested after 3, 7, 14, and 28 days. Gross obersvation was done and transverse diameter of remained DPMT in vivo was determined. HE staining and immunohistochemical staining of CD31 were used to assess inflammatory response and new capillary rings formation. RESULTS: Decellularization of the porcine skeletal muscle tissue by homogenating milling-detergent serial steps protocol was effective, time-saving, and simple, which could be finished within only 1 day. The decellularizarion and degreasing effect of DPMT was complete. The main component of DPMT was collagen type I and type IV. The DNA content in DPMT was (15.902+/-1.392) ng/mg dry weight, the total protein content was 68.94% of DPMT dry weight, which was significantly less than those of fresh skeletal muscle tissue[(140.727+/-10.422) ng/mg and 93.14%] (P<0.05). The microstructure of DPMT was homogeneous and porous. The result of cytocompatibility revealed that the cytotoxicity of DPMT was 0-1 grade, and HUVECs could stably grow on DPMT. In vivo study revealed DPMT could almost maintain its structural integrity at 14 days and it degraded completely at 28 days after implantation. The inflammatory response peaked at 3 days after implantation, and reduced obviously at 7 days. Difference was significant in the number of inflammatory cells between 2 time points (P<0.05). Neovascularization was observed at 7 days after implantation and the number of new vessels increased at 14 days, showing significant difference between at 7 and 14 days (P<0.05). CONCLUSIONS: The homogenating-milling-detergent serial-steps protocol is effective, time-saving, and reproducible. The DPMT reveals to be cell and lipid free, with highly preserved protein component. DPMT has good biocompatibility both in vitro and in vivo and may also have potential in promoting neovascularization. PMID- 29786213 TI - [RESEARCH PROGRESS OF REGULATION EFFECT OF HYPOXIA INDUCIBLE FACTOR ON INTERVERTEBRAL DISC]. AB - OBJECTIVE: To summarize the research progress of the regulation effect of hypoxia inducible factor (HIF) on intervertebral disc. METHODS: The domestic and foreign related literature about the regulation effect of HIF on intervertebral disc was reviewed, summarized, and analyzed. RESULTS: HIF is a key transcription factor that is in response to hypoxia by cells, which is widely distributed in tissues and organs, including intervertebral disc. Hypoxia inducible factor is expressed highest in the nucleus pulposus which has the lowest oxygen concentration in the intervertebral disc. The effects of HIF include the regulation of nucleus pulposus differentiation and development, maintenance of the survival, energy metabolism, and anabolism of nucleus pulposus cells, and maintenance of the stability of extracellular matrix. CONCLUSIONS: HIF plays a vital role in the development and differentiation of intervertebral disc and maintenance of physiological function, which may become a target for the research of the mechanism and the treatment of intervertebral disc degeneration. PMID- 29786212 TI - [PROMOTION EFFECT OF CHONDROITIN SULFATE ON PROLIFERATION OF MYOBLASTS]. AB - OBJECTIVE: To research the effect of chondroitin sulfate (CS) on the proliferation of myoblasts and the formation of myotube. METHODS: The myoblasts at passage 5 were used to prepare the cells suspension (1*108 cells/mL), and the experiment was divided into 4 groups based on CS concentration in the medium:group A (0 MUg/mL), group B (50 MUg/mL), group C (100 MUg/mL), and group D (200 MUg/mL). The cell morphology and myotube formation were observed by inverted microscope at 4, 5, and 8 days after treatment; MTT was used to detect the cell proliferation at 6 days, and the number of myotube was calculated by HE staining at 8 days. RESULTS: Cells showed spindle shape after adherent, with ovoid nuclei and dense cytoplasm under inverted microscope. When the cell adherent rate was 90%, cells arranged in whorls swirled and showed long fusiform adherent growth; and then nuclei fusion resulted in formation of multincleated myotubes. At 8 days, most myoblasts fused to form myotube in group A, but less myotube was observed in groups B and C, and the least myotube in group D. The absorbance (A) values of groups A, B, C, and D were 0.045 2+/-0.004 4, 0.540 4+/-0.096 7, 0.660 9+/-0.143 4, and 1.069 0+/-0.039 0 respectively, showing significant difference between other groups (P<0.05) except between groups B and C P>0.05). HE staining observation showed that most myoblasts fused to form myotube in group A, but less myotube in groups B and C, and the least myotube in group D. The number of myotube of groups A, B, C, and D were 222.01+/-30.02, 193.13+/-42.46, 170.26+/ 11.96, and 136.88+/-16.78 respectively, showing no significant difference among groups (F=1.658, P=0.252). CONCLUSIONS: CS can significantly promote the proliferation of myoblast, the promotion is the biggest when CS concentration is 200 MUg/mL. PMID- 29786214 TI - [RESEARCH PROGRESS OF INTERSPINOUS DISTRACTION DEVICES FOR TREATMENT OF DEGENERATIVE LUMBAR SPINAL STENOSIS]. AB - OBJECTIVE: To review the research status in respect of interspinous distraction devices (IDD) in the treatment of degenerative lumbar spinal stenosis (DLSS). METHODS: Recent original articles related to IDD in the treatment of DLSS were retrieved extensively, and the effectiveness was analyzed and summarized. RESULTS: Its short-term effectiveness was superior to that of conservative treatment, no significant difference was found when compared with decompression or fusion alone. Its complication rate was higher than that of decompression or fusion alone, although complication dose not significantly affect treatment results, it still will increase the medical care cost of patients. CONCLUSIONS: IDD is appropriate for patients who have failed to nonoperative treatment measures and can not tolerate open surgery, but the long-term effectiveness and durability of IDD need further research. PMID- 29786215 TI - [APPLICATION OF THREE-DIMENSIONAL DIGITAL TECHNOLOGY IN KNEE ARTHROPLASTY]. AB - OBJECTIVE: To review the recent progress in the application of three-dimensional digital technology in knee arthroplasty. METHODS: The relevant literature at home and abroad about the three-dimensional digital technology in the applications of knee arthroplasty in recent years was extensively reviewed. RESULTS: The three dimensional digital technology can obtain arthroplasty knee morphology and biomechanics, and can estimate preoperative planning osteotomy and the sizes of prostheses, so it can guide knee arthroplasty precisely. CONCLUSIONS: Three dimensional digital technology can reduce the operation error, improve the operation precision, and improve the effectiveness in knee arthroplasty. PMID- 29786216 TI - [ADVANCES IN NERVE RECONSTRUCTION OF OBSTETRIC BRACHIAL PLEXUS PALSY]. AB - OBJECTIVE: To review the advances in the diagnosis and treatment of obstetric brachial plexus palsy (OBPP). METHODS: The incidence, risk factors, classification, and imaging tests of OBPP and indication, technique, and results of surgery were reviewed and summarized. RESULTS: The incidence of OBPP is not declining in recent years. Birth weight of >=4 kg, forceps delivery, and prepregnancy body mass index of >=21 are considered to be major risk factors, and caesarean section delivery seems to be a protective factor. Neurophysiological investigations can be applied to qualitative diagnosis of OBPP, but can not to quantitative one. Sensitivity and specificity of both CT and MRI myelography are about 0.7 and 0.97, respectively. Narakas classification is widely used:C5, 6 injury as type I, C5-7 injury as type II, C5-T1 injury as type III, C5-T1 injury with Horner's syndrome as type IV. It is generally considered that the brachial plexus exploration should be undertaken for infants without spontaneous recovery of elbow flexion by a maximum of 3 months old; and 10% to 30% of patients may need nerve reconstruction surgery. It is advocated that traumatic neuroma of the upper trunk should be resected with nerve reconstruction. The final evaluation for surgical results should be at minimal 4 years for upper roots and 8 years for total roots. Scales of Mallet, Gilbert, and Raimondi are mostly used for assessing shoulder function, elbow function, and hand function. CONCLUSIONS: Brachial plexus exploration should be undertaken for infants without flexion of elbow at the age of 3 months. Traumatic neuroma (even neuroma-in-continuity) resection followed by microsurgical reconstruction of the brachial plexus is favored. PMID- 29786217 TI - [APPLICATION OF DOUBLE PEDICLED FLAP AND TECHNIQUE OF GEOMETRIC BROKEN LINE FOR PRIMARY REPAIR OF SERIOUS DOG BITE WOUNDS]. AB - OBJECTIVE: To evaluate the effectiveness of double pedicled flap and technique of geometric broken line (GBL) for primary repair of serious dog bite wound. METHODS: Between October 2006 and December 2014, 9 patients with serious dog bite wound were treated. There were 3 males and 6 females with an average age of 34.5 years (range, 8-68 years), and with a mean disease duration of 4 hours (range, 30 minutes to 24 hours). The defect ranged from 1.7 cm*0.5 cm to 15.0 cm*8.0 cm, with the mean depth of 0.5 cm (range, 0.3-0.8 cm). Deep tissue exposure was observed. After routine debridement, a vacuum sealing drainage (VSD) was equipped to suck and irrigate for 1 day, then wound was repaired. The superomedial edge of defect was trimmed, then a GBL shape mainly with square and rectangular was designed. According to defect size, a double pedicled flap was designed at the lateroinferior edge of defect, which size ranged from 1.7 cm*1.5 cm to 18.0 cm*15.0 cm. The donor site was sutured directly. VSD was used for 3 days after operation. RESULTS: All flaps survived and wound healed, and donor site incision healed well, with invisible scar. All patients were followed up 6 months to 8 years (mean, 4 years). The wounds were repaired well, and the patients had good facial appearance. No rabies attack was observed during follow-up. CONCLUSIONS: It is an ideal repair method to chose double pedicled flap and technique of GBL for primary repair of dog bite wounds. Satisfactory cosmetic appearance can be obtained. PMID- 29786218 TI - [CLINICAL EFFICACY OF MODIFIED POLYTETRAFLUOROETHYLENE PROSTHESIS RHINOPLASTY]. AB - OBJECTIVE: To explore the clinical efficacy of modified polytetrafluoroethylene (PTFE) prosthesis rhinoplasty for correction of low nose and short columella. METHODS: Between August 2012 and August 2015, modified PTFE prosthesis rhinoplasty was used to correct low nose and short columella in 52 patients. There were 4 males and 48 females, aged 19 to 45 years (mean, 27 years). Primary rhinoplasty was performed in 47 cases; secondary rhinoplasty was performed in 5 cases, and it was 12-18 months from the first operation (mean, 15 months). During operation, a scaly sag ventral side was made by carving and moving cap shaped nose prosthesis was prepared, and nasal dorsumnasal columella prosthesis covered by tension-free flap was designed. At pre-operation and last follow-up, Image ProPlus 6.0 software was used to measure the nose length, nose depth, nose tip width, nostril/nose tip, nasolabial angle, and nasal tip rotation for evaluation of external nose shape correction; and ultrasound was used to measure the alar cartilage angle, alar two vertex distance, and nose tip to vertex distance for evaluation of internal soft tissue changes; the prosthesis position was observed by CT scan at 12 months. RESULTS: All incisions healed by first intention, with no complications. All patients were followed up 7-36 months (mean, 20.4 months). At 12 months after operation, CT scans showed that prosthesis located in the middle of the nose and above nasal bone, septal cartilage and crus mediale cartilaginis alaris majoris in 45 patients; no prosthesis displacement was observed. At last follow-up, image measurement and ultrasound results showed external nose shape parameters (except nostril/nose tip) and internal soft tissue structures were significantly improved when compared with preoperative values (P<0.05). CONCLUSIONS: Modified PTFE prosthesis rhinoplasty can effectively correct low nose and short columella, with small surgical trauma and good appearance. PMID- 29786219 TI - [MODIFIED INTRAMEDULLARY FIXATION WITH TWO Kirschner WIRES FOR EXTRA-ARTICULAR FRACTURE OF PROXIMAL PHALANGEAL BASE]. AB - OBJECTIVE: To evaluate the effectiveness of the modified intramedullary fixation with two Kirschner wires for extra-articular fracture of the proximal phalangeal base. METHODS: Between June 2012 and November 2015, 18 cases (18 fingers) of fresh extra-articular fracture of the proximal phalangeal base were treated, including 16 males and 2 females with an average age of 31 years (range, 21-57 years). The causes included strike injury in 10 cases, fall injury in 4 cases, mechanical injury in 1 case, twist injury in 1 case, crush injury in 1 case, and cutting injury in 1 case. The injured fingers were little finger in 16 cases, ring finger in 1 case, and index finger in 1 case. Of the 18 cases, 17 had closed fractures and 1 had open fracture. X-ray film showed transverse fracture in 14 cases and transverse-oblique fracture in 4 cases. The time between injury and operation was 3 hours to 4 days (mean, 2 days). After anatomical reduction, two Kirschner wires were used for intramedullary fixation. Functional exercises were done at 2 days after operation. The Kirschner wires were removed at 4 weeks after operation. RESULTS: All the wounds healed by first intention. There were no deformation, loosening or breakage of Kirschner wires, and pin tract infection. Postoperative X-ray films showed anatomical reduction of fracture in all cases; no re-displacement happened, and clinical healing was obtained at 4 weeks; bony union was obtained at 8 weeks. All patients were followed up 6-12 months with an average of 8 months. There was no pain in the metacarpophalangeal joint; the range of motion was (88.1+/-2.3) degrees at 3 months after operation, showing no significant difference when compared with normal side [(88.8+/-2.6) degrees ] (t=1.73, P=0.10). The finger flexion and extension were normal; according to the criteria of total active motion of finger, the results were excellent in all cases. CONCLUSIONS: The technique of modified intramedullary fixation with two Kirschner wires for extra-articular fractures of the proximal phalangeal base has the merits of convenient operation, little injury, reliable fixation,and excellent effectiveness. This technique is conducive to the recovery of hand function due to the early functional exercises. PMID- 29786220 TI - [EFFECTIVENESS OF PART LONG THUMB EXTENSOR TENDON DORSAL ULNAR ARTERY CHIMERIC FLAP FOR REPAIR OF Doyle TYPE III MALLET FINGER OF THUMB]. AB - OBJECTIVE: To investigate the effectiveness of part long thumb extensor tendon dorsal ulnar artery chimeric flap for repair of Doyle type III mallet finger of thumb. METHODS: Between June 2013 and April 2015, 9 cases of Doyle type III mallet finger of thumb were treated, which were caused by planer injury. There were 6 males and 3 females, aged from 15 to 65 years (mean, 36 years). The time from injury to operation was 3-8 hours (mean, 5 hours). All cases had interphalangeal joint dorsal skin and soft tissue defects of the thumb; the skin defects ranged from 2.0 cm*1.5 cm to 2.3 cm*2.3 cm; the extensor tendon defect ranged from 0.5 to 1.5 cm in length (mean, 1.0 cm). The part long thumb extensor tendon dorsal ulnar artery chimeric flap of 3.0 cm*2.5 cm to 3.5 cm*3.0 cm in size was used to reconstruct extensor tendon and wound. The donor site was repaired with nasopharyngeal fossa perforating branches pedicled V-Y relay flap. RESULTS: All flaps survived completely and incisions healed by first intention. All patients were followed up 4-12 months (mean, 6 months). The flaps had good color, texture, and contour. At 6 months after operation, the two-point discrimination of chimeric flap was 10-12 mm (mean, 11 mm), and two-point discrimination of relay flap was 12-14 mm (mean, 13 mm). The interphalangeal joint flexion of thumb was 0-40 degrees , and the thumb opposition function was normal. CONCLUSIONS: Part long thumb extensor tendon dorsal ulnar artery chimeric flap can repair the Doyle type III mallet finger of thumb, which has no injury to the artery and nerve. At the same time the relay flap can achieve linear healing, so good appearance and function of the thumb can be obtained. PMID- 29786221 TI - [REVERSED ARTHROSC OPIC SUBACROMIAL DEC OMPRESSION FOR TREATMENT OF ROTATOR CUFF TEARS]. AB - OBJECTIVE: To investigate the effectiveness of reversed arthroscopic subacromial decompression in the treatment of rotator cuff tears. METHODS: Between November 2012 and January 2015, 53 patients with rotator cuff tears were treated with reversed arthroscopic subacromial decompression and rotator cuff repair. Of 53 patients, 38 were male and 15 were female, with the age of 47-61 years (mean, 53.4 years). The injury was caused by falling in 36 cases and other in 17 cases without an obvious history of trauma. All patients had shoulder pain and limited shoulder movement before operation. Visual analogue scale (VAS) was 6.4+/-0.9, and University of California at Los Angeles (UCLA) score was 16.3+/-1.9. MRI showed that distal supraspinatus tear was observed in 41 cases and distal infraspinatus tear in 12 cases; partial-thickness rotator cuff tear was observed in 9 cases and full-thickness tear in 44 cases. And the tear size was from 1 to 3 cm (mean, 1.9 cm). Combined injuries included tendinitis of long head of biceps brachii in 31 cases, Bankart lesion in 5 cases, and superior labrum anterior and posterior lesion in 2 cases. RESULTS: Incision healed by first intention in all patients; no infection or nerve injury occurred. Forty-nine cases were followed up from 12 to 35 months (mean, 22.8 months). After operation, shoulder pain relief was achieved in 42 cases; 7 cases had anterior shoulder pain at 3 months after operation, which was relieved after symptomatic treatment. At last follow up, VAS score was significantly decreased to 0.5+/-0.6 (t=40.565, P=0.000). UCLA score was significantly increased to 33.8+/-1.7 (t=-79.799, P=0.000). The results were excellent in 42 cases, good in 6 cases, and fair in 1 case; the excellent and good rate was 98.0%. CONCLUSIONS: Reversed arthroscopic subacromial decompression can avoid coracoacromial arch injury and achieve good recovery of joint function, so it can be used in rotator cuff tears procedure. PMID- 29786223 TI - [PROSPECTIVE RANDOMIZED CONTROLLED STUDY ON TREATMENT OF DISPLACED FEMORAL NECK FRACTURES WITH PERCUTANEOUS COMPRESSION PLATE]. AB - OBJECTIVE: To compare the effectiveness of percutaneous compression plate (PCCP) and hollow compression screw in the treatment of displaced femoral neck fractures. METHODS: Between January 2010 and June 2014, 70 patients with displaced femoral neck fractures were randomly divided into 2 groups. After reduction, fracture was fixed with PCCP in 35 cases (group A) and with hollow compression screw in 35 cases (group B). There was no significant difference in the gender, age, cause, side and type of fractures, time from injury to operation, associated disease, pre-operative Harris score and visual analogue scale (VAS) score between 2 groups (P>0.05). The operation time, intra-operative blood loss, fracture healing time, fracture reduction quality, time of rehabilitation and weightloading; complication, post-operative Harris score and post-operative VAS score were compared between 2 groups. RESULTS: The incisions healed by first intention. All patients were followed up 13-34 months (mean, 23.7 months). There were significant differences in operation time, intra-operative blood loss, and fracture healing time between 2 groups (P<0.05). There was no significant in the fracture reduction quality between 2 groups (P>0.05). Avascular necrosis of the femoral head occurred in 2 cases of group A after operation (fracture reduction quality: grade IV); and avascular necrosis of the femoral head occurred in 4 cases of group B after operation (fracture reduction quality: grade I in 2 cases, grade II in 1 case, grade III in 1 case, and grade IV in 1 case), nonunion in 1 case, and screw loosening in 3 cases; and there was significant difference in the incidence of bone nonunion and avascular necrosis of the femoral head between 2 groups (chi2=-3.997, P=0.046). Difference was significant in fracture reduction quality in the patients with avascular necrosis of the femoral head and nonunion between 2 groups (chi2=1.991, P=0.047). The time of rehabilitation and weight-loading of group A was significantly earlier than that of group B (P<0.05); the Harris and VAS scores of group A were significantly better than those of group B at 12 months after operation (P<0.05). CONCLUSIONS: PCCP for treatment of displaced femoral neck fractures has better static stability and better sliding dynamic pressure effect than hollow compression screw, and it can provide earlier rehabilitation and weight-loading postoperatively and obviously decrease the incidence of bone nonunion and avascular necrosis of the femoral head, but avascular necrosis of the femoral head still occur in patients with poor reduction or comminuted fracture. PMID- 29786222 TI - [CEMENTLESS TOTAL HIP ARTHROPLASTY FOR TREATMENT OF Crowe TYPE III DEVELOPMENTAL DYSPLASIA OF HIP IN ADULTS]. AB - OBJECTIVE: To investigate the value of cementless total hip arthroplasty (THA) for the treatment of Crowe type III developmental dysplasia of hip (DDH) in adults. METHODS: Between September 2013 and September 2015, 50 patients (51 hips) with Crowe type III DDH were treated. There were 20 males (20 hips) and 30 females (31 hips), with the average age of 39 years (range, 19-55 years). The left side was involved in 34 cases, the right side in 15 cases, and both sides in 1 case. All patients had the symptoms of limp walking and hip pain. The disease duration was 10-47 months (mean, 26 months). The sign of "4" number test and Trendenleburg sign were positive; the Harris score was 38.9+/-7.1. The bilateral lower extremities discrepancy was 2.5-4.0 cm (mean, 3.3 cm) before operation. All the patients underwent cementless THA, and acetabulum by structural femoral head autograft was performed in 28 cases (28 hips). RESULTS: After operation, the incision healed by first intention. Only 2 patients (2 hips) had femoral nerve palsy, and 7 patients (7 hips) had leg swelling, which were cured after symptomatic treatment. All the patients were followed up 6-18 months (mean, 10 months). The sign of limp walking was improved after operation, hip pain was relieved in 46 patients (46 hips) and only 4 patients (5 hips) still had mild pain. The X-ray films showed bony healing at 3-6 months (mean, 5 months) after operation. At last follow-up, the patients had equal limb length with the discrepancy less than 1 cm (mean, 0.4 cm). At last follow-up, the Harris score was significantly increased to 91.2+/-2.8 (t=-79.77, P=0.00). CONCLUSIONS: The cementless THA is an effective method to treat Crowe type III DDH in adults. PMID- 29786224 TI - [TREATMENT OF SEVERE MEDIAL COLLATERAL LIGAMENT RUPTURE IN MULTI-LIGAMENT INJURY]. AB - OBJECTIVE: To compare the clinical efficacy between medial collateral ligament (MCL) repair and MCL reconstruction in multi-ligament injury. METHODS: Thirty-one patients with MCL rupture and multi-ligament injury of knee joint were treated between August 2008 and August 2012, and the clinical data were retrospectively analyzed. Of 31 patients, 11 cases underwent MCL repair (repair group), and 20 cases underwent MCL reconstruction (reconstruction group). There was no significant difference in gender, age, body mass, injury side, injury cause, and preoperative knee Lyshlom score, International Knee Documentation Committee (IKDC) subjective score, range of motion, and medial joint opening between 2 groups (P>0.05). The postoperative knee subjective function and stability were compared between 2 groups. RESULTS: All incisions healed by first intention, and no postoperative complication occurred. All patients were followed up 2-4 years (mean, 3.2 years). At 2 years after operation, the IKDC subjective score, Lyshlom score, and range of motion were significantly increased in 2 groups when compared with preoperative ones (P<0.05). The range of motion of reconstruction group was significantly better than that of repair group (P<0.05). No significant difference was found in IKDC subjective score and Lyshlom score between 2 groups (P>0.05). The medial joint opening was significantly improved in 2 groups at 2 years after operation when compared with preoperative one (P<0.05), but no significant difference was found between 2 groups (P>0.05). CONCLUSIONS: Both the MCL reconstruction and MCL repair can restore medial stability in multi-ligament injury, but MCL reconstruction is better than MCL repair in range of motion. PMID- 29786225 TI - [SIMULTANEOUS REPAIR OF TIBIA BONE DEFECT AND REFRACTORY SOFT TISSUE DEFECT BY BONE TRANSPORT TECHNIQUE]. AB - OBJECTIVE: To explore the feasibility and effectiveness of bone transport technique for simultaneous repair of tibia defect and refractory soft tissue defect. METHODS: Thirty-five patients with tibia bone defect combined with refractory soft tissue defect were treated between January 2010 and December 2014, and the clinical data were retrospectively analyzed. There were 21 males and 14 females with an average age of 29 years (range, 18-47 years). All patients had Gustilo type III open tibial fractures, which were caused by traffic accident. Fracture located at the upper 1/3 of the tibia in 1 case, at the middle 1/3 of the tibia in 19 cases, and at the lower 1/3 of the tibia in 15 cases. All patients underwent external fixation after 4-10 hours of trauma, and tibial skin necrosis, infection, and purulent exudation were observed after 5-10 days of operation. The time from injury to admission was 21 days to 5 months (mean, 2 months). After debridement, the average length of tibia defect was 8 cm (range, 6 11 cm); the area of soft tissue defect was 6 cm*5 cm to 10 cm*8 cm. Orthofix external fixation was applied to tract the bone and soft. RESULTS: All 35 patients were followed up 12-22 months (mean, 16 months). The average time of bony healing was 15 months (range, 9-20 months), and no obvious force line offset was found. Osteotomy segment was extended from 6 to 11 cm (mean, 8 cm); after treatment, the external fixation support was retained for 2 to 10 months (mean, 5 months). No blood vessel and nerve injuries were found during treatment, and no osteomyelitis and refracture happened after operation. The skin and soft tissue defects healed, and the healing time was 1 to 3 months (mean, 1.3 months). Different degrees of infection occurred in 5 cases, and was cured after dressing change. According to Johner-Wruhs' evaluation criteria after external fixator was removed, the results were excellent in 26 cases, good in 5 cases, and moderate in 4 cases, with an excellent and good rate of 88.6%. CONCLUSIONS: Bone transport technique can simultaneously repair tibia bone defect and soft tissue defect by continuous bone and soft tissue traction. PMID- 29786226 TI - [Masquelet TECHNIQUE COMBINED WITH TISSUE FLAP GRAFTING FOR TREATMENT OF BONE DEFECT AND SOFT TISSUE DEFECT]. AB - OBJECTIVE: To explore the therapeutic effect of Masquelet technique combined with tissue flap grafting for bone defect and soft tissue defect. METHODS: Between August 2012 and April 2015, 18 cases of bone defect and soft tissue defect were treated by using Masquelet technique combined with tissue flap grafting. There were 11 males and 7 females, aged from 23 to 59 years (mean, 37.1 years). The time between injury and treatment was 15 days to 39 months (mean, 0.9 months). Defect located at the proximal tibia in 4 cases, at the middle tibia in 8 cases, at the distal tibia in 4 cases, and at the lateral heel in 2 cases. All patients were treated with debridement. After debridement, the bone defect was (5.7+/-1.8) cm in length, and the soft tissue defect was 5 cm*4 cm to 13 cm*11 cm in size. In one-stage operation, bone defect was repaired with the antibiotic cement and fracture was fixed by temporary external fixation. The surfaces of wound were repaired with tissue flap. After 6 to 8 weeks when wounds healed with no sign of infection, bone grafting from iliac bone and/or fibula was performed in two-stage operation. RESULTS: Eighteen patients followed up 10-38 months (mean, 24.3 months). After one-stage operation, 6 cases had pin track infection, which was cured by strengthened disinfection and oral antibiotics. All the tissue flaps survived. Bone healing was observed on X-ray film at 15-57 weeks (mean, 25.3 weeks) after two-stage operation. The function of the knee and ankle joint recovered well. According to the American Orthopaedic Foot and Ankle Society (AOFAS) score for the ankle joint, the scores of ankle function ranged from 74 to 98, with an average of 89.7; the results were excellent in 7 cases, good in 10 cases, and fair in 1 case. CONCLUSIONS: The Masquelet technique combined with tissue flap grafting is an effective method to treat bone defect and soft tissue defect. PMID- 29786227 TI - [SHORT-TERM EFFECTIVENESS OF TightRope SYSTEM FOR TREATMENT OF SYNDESMOTIC TIBIOFIBULAR DIASTASIS]. AB - OBJECTIVE: To summarize the short-term effectiveness of TightRope system for the treatment of syndesmotic tibiofibular diastasis. METHODS: Between June 2013 and June 2015, 23 patients with syndesmotic tibiofibular diastasis were treated by TightRope system, including 15 males and 8 females with an average age of 32.3 years (range, 16-63 years). Injury was caused by sports in 13 cases, by traffic accident in 6 cases, and by falling from height in 4 cases. The locations were the left side in 13 cases and the right side in 10 cases. The time from injury to operation was 6 hours to 12 days (mean, 3.8 days). According to Lauge-Hansen classification, 13 cases were rated as supination-external rotation type, 7 cases as pronation-abduction type, and 3 cases as pronation-external rotation type; according to Weber classification, 5 cases were rated as type A, 11 cases as type B, and 7 cases as type C. RESULTS: The mean operative time was 68.1 minutes (range, 48-93 minutes); the mean intraoperative blood loss was 70.3 mL (range, 20 150 mL); and the mean hospitalization days were 7 days (range, 5-13 days). Superficial local skin necrosis occurred in 6 cases, and primary healing of incision was obtained in the others. All patients were followed up 8-30 months (mean, 16.4 months). X-ray films showed bone union was achieved within 6-12 weeks (mean, 9.4 weeks). No related complications of reduction failure and re-fracture occurred. The internal fixators were removed at 10-18 months postoperatively (mean, 13.3 months). According to American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle function evaluation, the results were excellent in 19 cases and good in 4 cases at last follow-up. CONCLUSIONS: TightRope system is a good method to treat syndesmotic tibiofibular diastasis, because of safety, convenient operation, and satisfactory short-term effectiveness. PMID- 29786229 TI - [CLINICAL OBSERVATION OF POSTERIOR CERVICAL DECOMPRESSIVE LAMINECTOMY AND LATERAL MASS SCREW FIXATION COMBINED WITH FORAMINOTOMY FOR CERVICAL RADICULO-MYELOPATHY]. AB - OBJECTIVE: To evaluate the effectiveness of posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy for treating cervical radiculo-myelopathy. METHODS: Between January 2010 and January 2012, 58 patients with cervical radiculo-myelopathy were treated by posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy. There were 31 males and 27 females, with an average age of 52.7 years (range, 41-72 years). The mean disease course was 5.4 years (range, 3-15 years). The preoperative Japanese Orthopaedic Association (JOA) score was 7.8+/ 1.3, and visual analogue scale (VAS) score was 6.8+/-1.7. There were 37 cases of inter-vertebral disc herniation and ligamentum flavum hypertrophy, 11 cases of vertebral osteophyte formation with the osteophyte spinal canal occupational ratio of 51.7%+/-18.1%, and 10 cases of inter-vertebral disc herination with cervical instability. Preoperative cervical curvature was (-5.5+/-12.5) degrees . The fixed segments included C3-7 in 29 cases, C4-7 in 19 cases, and C3-6 in 10 cases. Foraminotomy was performed in 135 nerve foramina (mean, 2.33 foramina). RESULTS: The mean operation time was 204 minutes (range, 167-260 minutes), and the mean blood loss was 273 mL (range, 210-378 mL). No injury of vertebral artery or nerve root occurred during operation. Postoperative subcutaneous hematoma and cervical axial pain occurred in 1 case and 8 cases, respectively; and no nerve root palsy was observed. The patients were followed up 2.1-4.3 years (mean, 3.4 years). The postoperative JOA score was significantly increased to 14.1+/-1.7 (t= 27.672, P=0.000), with an improvement rate of 68.5%+/-21.9%. Postoperative VAS score was significantly decreased to 2.1+/-1.1 (t=15.168, P=0.000). The imaging examination showed adjacent segmental degeneration in 1 patient, who had no clinical symptom. There was no screw loosening or pseudoarthrosis formation during follow-up. The cervical curvature was (13.6+/-5.1) degrees at 5 days and was (13.2+/-4.8) degrees at 2 years, showing significant difference when compared with preoperative one (P<0.05). The osteophyte spinal canal occupational ratio was 36.5%+/-10.4% at 2 years, showing significant difference when compared with preoperative one (t=6.921, P=0.000). CONCLUSIONS: The procedure of posterior cervical decompressive laminectomy and lateral mass screw fixation combined with foraminotomy is effect in treating cervical radiculo-myelopathy. The spinal cord and nerve root can be adequately decompressed by laminectomy and foraminotomy. The lateral mass screw fixation can correct the cervical curvature and further reduce the tension to spinal cord. PMID- 29786228 TI - [SHORT-TERM EFFECTIVENESS OF Hyprocure SUBTALAR STABILIZATION IN TREATMENT OF ADOLESCENT FLEXIBLE FLATFOOT]. AB - OBJECTIVE: To evaluate the short-term effectiveness of Hyprocure subtalar stabilization for adolescent flexible flatfoot. METHODS: Between December 2013 and September 2015, 14 cases (26 feet) of adolescent flexible flatfoot were treated with Hyprocure subtalar stabilization. There were 10 males (18 feet) and 4 females (8 feet) with the average age of 14.5 years (range, 12-18 years). There were 12 cases (24 feet) of congenital flatfoot and 2 cases (2 feet) of flatfoot caused by neurological diseases. The preoperative pain visual analogue scale (VAS) was 4.2+/-0.4; the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and foot function score was 72.2+/-12.3. Simple Hyprocure subtalar stabilization was used in 8 feet, and a combination of minimally invasive percutaneous Achilles tendon lengthening or gastrocnemius lysis, preposing of posterior tibial tendon and spring ligament tightening surgery, or open dorsal medial cuneiform osteotomy and bone graft in 18 feet. The VAS score and AOFAS ankle and foot function score were used to evaluate the effectiveness. The talus the first metatarsal angle (T1MT), the talus-the second metatarsal angle (T2MT), and talonavicular coverage angle (TCA) were measured on the anteroposterior X-ray film; the Meary's angle, calcaneal inclination angle (CI), and the talar declination (TD) were measured on the lateral X-ray film. RESULTS: All incisions healed well. Two cases (2 feet) had tarsal sinus pain, which was cured after symptomatic treatment. All patients were followed up 5-24 months (mean, 14.5 months). Pain was obviously relieved. At last follow-up, VAS score was significantly decreased to 1.4+/-0.3 (t=27.676, P=0.000). AOFAS ankle and foot function score was significantly increased to 94.5+/-10.8 (t=7.765, P=0.000). The postoperative X-ray film showed that medial arch was elevated after the Hyprocure subtalar stabilization was placed in tarsal sinus. At last follow-up, the T1MT, T2MT, TCA, Meary's angle, and TD were significantly improved when compared with preoperative ones (P<0.05); CI has no significant improvement (t=0.109, P=0.598). CONCLUSIONS: Hyprocure subtalar stabilization is simple, effective for adolescent flexible flatfoot, the short-term effectiveness is good. But the indications should be strictly controlled, treatment should be individualized, corresponding auxiliary soft tissue and bone surgery is needed. The long-term effectiveness needs further follow-up. PMID- 29786230 TI - [MINIMALLY INVASIVE PASSAGE IN POSTERIOR LAMINOTOMY DECOMPRESSION AND INTERVERTEBRAL BONE GRAFTING COMBINED WITH PERCUTANEOUS PEDICLE SCREW FIXATION FOR TREATMENT OF Denis TYPE B THORACOLUMBAR BURST FRACTURES]. AB - OBJECTIVE: To evaluate the feasibility and the effectiveness of minimally invasive passage in posterior laminotomy decompression and intervertebral bone grafting combined with percutaneous pedicle screw fixation for the treatment of Denis type B thoracolumbar burst fractures. METHODS: Between January 2013 and March 2015, 53 patients with Denis type B thoracolumbar burst fractures were treated by minimally invasive passage in posterior laminotomy decompression and intervertebral bone grafting combined with percutaneous pedicle screw fixation. There were 37 males and 16 females with a mean age of 43 years (range, 16-57 years). The causes included falling injury from height in 23 cases, traffic accident injury in 15 cases, heavy pound injury in 7 cases, and falling injury in 8 cases. The time between injury and operation was 7 hours to 12 days (mean, 6.7 days). The involved segments included T11 in 2 cases, T12 in 7 cases, L1 in 20 cases, L2 in 18 cases, and L3 in 6 cases; based on the neurological classification of spinal cord injury by American Spinal Injury Association (ASIA), 3 cases were rated as grade A, 5 cases as grade B, 12 cases as grade C, 24 cases as grade D, and 9 cases as grade E. The operation time, bleeding volume, and postoperative drainage were recorded; postoperative visual analogue scale (VAS) was used for pain evaluation, and ASIA for neurological function assessment; CT and X-ray films were taken to observe fracture healing, bone fusion, and grafted bone absorption; The vertebral canal patency rate was calculated; the relative height of fractured vertebrae and Cobb angle were measured. RESULTS: The operation was successfully completed in all patients; the average operation time was 150 minutes (range, 90-240 minutes); the average bleeding volume was 350 mL (range, 50-500 mL); the average postoperative drainage was 80 mL (range, 20-150 mL); and the average VAS score was 2.3 (range, 1.5-4.7) at 3 days after operation. The incisions healed primarily. All the patients were followed up 12-19 months (mean, 15 months). All fractures healed at 3-9 months (mean, 6 months). No complications of broken nails, broken rod, and screw loosening occurred. At last follow-up, the vertebral canal patency rate was significantly improved when compared with preoperative value (t=27.395, P=0.000). The Cobb angle, and the anterior and posterior heights of of traumatic vertebra were significantly improved at 1 week, 1 year, and last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between different time points after operation (P>0.05). The neurological function was improved in different degrees; 1 case was rated as grade A, 4 cases as grade B, 7 cases as grade C, 15 cases as grade D, and 26 cases as grade E, showing significant difference when compared with preoperative one (Z=-5.477, P=0.000). CONCLUSIONS: Minimally invasive passage in posterior laminotomy decompression, bone graft in the injured vertebrae combined with percutaneous pedicle screw fixation is an effective method to treat Denis type B thoracolumbar burst fractures, which not only can fully decompression, but also can effectively maintain the postoperative injured vertebral height, reduce the postoperative failure risk of internal fixation and decrease operation trauma. PMID- 29786231 TI - [BIOMECHANICAL STUDY ON UPPER THORACIC SPINE BASED ON PRESSURE SENSITIVE FILM MATERIALS IN CHINESE MINI PIGS]. AB - OBJECTIVE: To analyze the pressure change and distribution of the intervertebral disc of upper thoracic spine in vertical pressure and 5 degrees flexion, extension, or lateral bending. METHODS: Twelve thoracolumbar spinal specimens were harvested from mini pigs and were divided into 2 groups (n=6). T1, 2, T3, 4, T5, 6, and T7, 8 segments were included in one group, and T2, 3, T4, 5, T6, 7, and T8, 9 segments were included in the other group. The data from both groups represented the complete upper thoracic vertebra data. Biomechanical machine and pressure sensitive film were used to measure the pressure on the vertebral columns under loadings of 100, 150, and 200 N in vertical pressures and 5 degrees flexion, extension, or lateral bending. The pressure change of each intervertebral disc under different loads and in different movement conditions was analyzed. RESULTS: In flexion, the anterior annulus pressure of the upper thoracic vertebra increased (P<0.05), whereas the posterior annulus pressure showed no significant change (P>0.05) or an increasing trend (P<0.05). In extension, the anterior annulus pressure of the upper thoracic vertebra decreased (P<0.05), whereas the posterior annulus pressure decreased (P<0.05) or had no obvious change (P>0.05). In lateral bending, the pressure on the concave side of the annulus increased significantly (P<0.05). CONCLUSIONS: The upper thoracic vertebra has unique biomechanical characteristics under different loadings; moreover, the posterior vertebral structure plays an important role in the movement of the upper thoracic vertebral segment and pressure distribution. In lateral bending of the upper thoracic vertebra, the concave side pressure will increase significantly, which suggests that asymmetrical force is an important cause of scoliosis progression. Gravity plays an important role in the progression of scoliosis. PMID- 29786232 TI - [EFFECT OF MACROPHAGE MIGRATION INHIBITORY FACTOR ON VASCULAR REPAIR OF STEROID INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN VITRO]. AB - OBJECTIVE: To interpret the mechanisms of vascular repair disorders in steroid induced avascular necrosis of the femoral head (SANFH) via detection of the changes of proliferation, migration, and macrophage migration inhibitory factor (MIF)/vascular endothelial growth factor (VEGF) expressions of endothelial cells (ECs) under hypoxia/glucocorticoid. METHODS: According to culture conditions, human umbilical vein ECs (HUVECs) at passage 3 were divided into group A (normal), group B (1.0*10-6 mol/L dexamethasone), group C (hypoxia), and group D (hypoxia+1.0*10-6 mol/L dexamethasone). The cell activity was detected by AlamarBlue; the number of viable cells was detected in live/dead cell staining; the cell morphology was observed after cytoskeleton staining; cell migration ability was compared by scratch test; and the levels of MIF and VEGF expressions were detected by ELISA. RESULTS: At 24 hours after culture, the cell activity and the number of living cells in group C were significantly higher than those in the other 3 groups, showing significant difference between groups (P<0.05), and group D had the worst cell activity and least living cells. Cytoskeleton staining showed that cells had normal morphology in groups A and B; cells had rich cytoskeleton and secretion granules in group C; cytoskeleton form disorder and nucleus pyknosis were observed in group D. Scratch test showed that the cell migration ability of group C was strongest while cell migration ability of group D was weakest. Accumulated concentration of MIF and VEGF in 4 groups significantly increased with time extending. Accumulated concentration of MIF in group C were significantly higher than that in other 3 groups at each time point (P<0.05). Within 24 hours after intervention, stage concentration of MIF during 1 8 hours was significantly lower than that during 0-1 hour and 8-24 hours in every group (P<0.05). Stage concentration of MIF in group C was significantly higher than other groups during 0-1 hour and 8-24 hours (P<0.05). Within 2 hours after intervention, stage concentration of MIF in 4 groups during 0.5-1 hour was significantly higher than that during other stages (P<0.05). Accumulated concentration of VEGF in group C was significantly higher than that in other groups at 8 and 24 hours (P<0.05). The stage concentration of VEGF in groups C and D during 8-24 hours was significantly higher than that during 0-1 hour and 1 8 hours (P<0.05). There was no significant difference in the stage concentration of VEGF within and among group A, B, C, and D at every stage within 2 hours after intervention (P>0.05). CONCLUSIONS: In hypoxia environment, the proliferation and migration of ECs is enhanced, and the secretion of VEGF and MIF is increased. High concentration of dexamethasone will suppress the process above, which induces vascular repair disorders and aggravating SANFH. PMID- 29786233 TI - [EFFECT OF STAPHYLO CO CCAL PEPTID O GLYCAN ON OSTEO CL AST DIFFERENTIATION]. AB - OBJECTIVE: To investigate the effect of Staphylococcal peptidoglycan (PGN-sa) on raw264.7 cells differentiating into osteoclasts. METHODS: There were 5 groups in the experiment: 100 ng/mL PGN-sa group, 200 ng/mL PGN-sa group, 400 ng/mL PGN-sa group, positive control group [100 ng/mL receptor activator of nuclear factor kappaB ligand (RANKL)], and blank control group (PBS). Raw264.7 cells were cultured with different concentrations of PGN-sa, RANKL, or PBS for 5 days, and then tartrate resistant acid phosphatase (TRAP) staining was used to detect the formation of osteoclast-like cells; Image-Pro Plus 6.0 software was used to detect the bone resorption areas of osteoclast-like cells; and MTT assay was used to observe the proliferation activity of raw264.7 cells. RESULTS: TRAP staining showed that PGN-sa and RANKL can induce raw264.7 cells to differentiate into osteoclast-like cells; different concentrations of PGNsa groups had more osteoclast-like cells formation than blank control group (P<0.05), and the number of osteoclast-like cells significantly increased with the increase of PGN-sa concentrations (P<0.05). Bone resorption cavity experiment showed that bone resorption cavities were obvious in different concentrations of PGN-sa groups and in positive control group, and the area of bone absorption cavities was increased with the increasing PGN-sa concentrations, showing significant difference between groups (P<0.05). MTT assay showed that no significant difference was found in the absorbance (A) value between different concentrations of PGN-sa groups and blank control group, and between different concentrations of PGN-sa groups (P>0.05). CONCLUSIONS: PGN-sa can promote raw264.7 cells to differentiate into osteoclasts with bone resorption activity. PMID- 29786234 TI - [ROLE OF EXTRACELLULAR SIGNAL-RELATED PROTEIN KINASE 1/2 PATHWAY IN GINSENOSIDE Rg1 MEDIATED ANTI-APOPTOTIC EFFECT ON NEURON AFTER HYPOXIA ISCHEMIA BRAIN DAMAGE IN NEONATAL RATS]. AB - OBJECTIVE: To investigate the anti-apoptotic effect of ginsenoside Rg1 in neonatal rats with hypoxia ischemia brain damage (HIBD), and to explore the possible signaling pathway involved in anti-apoptosis. METHODS: Forty-eight 10 day-old Sprague Dawley (SD) rats (weighing 17-21 g, male or female) were randomly allocated into 4 groups (12 rats in each group): sham-operation group (sham group), HIBD group (HI group), HIBD+ginsenoside Rg1 group (HI+Rg1 group), and HIBD+ginsenoside Rg1+U0126 group (HI+Rg1+U0126 group). SD rats in HI group, HI+Rg1 group, and HI+Rg1+U0126 group underwent ligation of the right common carotid artery (CCA) and hypoxic ventilation (8%O2+92%N2) for 2.5 hours to prepare the HIBD model, and rats in sham group underwent only separation of the right CCA. SD rats in HI+Rg1+U0126 group received intraventricular injection of 5 MUL phosphate buffer saline (PBS) containing U0126 (25 MUg/kg) at 1 hour before HIBD, and rats in the other three groups received intraventricular injection of PBS at the same time. The rats in HI+Rg1 group and HI+Rg1+U0126 group received intraperitoneal injection of 0.1 mL normal saline (NS) containing Rg1 (40 mg/kg) at immediate after HIBD, while rats in HI group and sham group received intraperitoneal injection of 0.1 mL NS at immediate after HIBD. At 4 and 24 hours after HIBD, the right hemisphere and hippocampus were collected to detect the protein expression and distribution of extracellular signal-related protein kinase 1/2 (Erk1/2), phospho-Erk1/2 (p-Erk1/2), hypoxia inducible factor 1alpha (HIF-1alpha), and cleaved Caspase-3 (CC3) by Western blot and immunohistochemistry staining. TUNEL staining was used to evaluate neural apoptosis in situ. RESULTS: Western blot results showed that there were expressions of Erk1/2, p-ERK1/2, HIF-1alpha, and CC3 proteins at 4 and 24 hours after HIBD in each group. The expressions of HIF-1alpha and CC3 protein at 4 and 24 hours, and expression of p-Erk1/2 protein at 4 hours were significantly increased in HI group when compared with sham group (P<0.05). When compared with HI group, the expressions of p-Erk1/2 and HIF-1alpha protein in HI+Rg1 group were significantly increased (P<0.05), while the expression of CC3 protein was significantly decreased at 4 and 24 hours (P<0.05). When compared with HI+Rg1 group, the expressions of p-Erk1/2 and HIF-1alpha proteins in HI+Rg1+U0126 group were significantly decreased (P<0.05), while expression of CC3 protein was significantly increased at 4 and 24 hours (P<0.05). There was no significant difference in Erk1/2 protein expression between groups at different time points (P>0.05). Immunohistochemistry staining displayed that HIF-1alpha and CC3 proteins mainly distributed in the nucleus and cytoplasma, while Erk1/2 and p Erk1/2 proteins mainly distributed in the cytoplasma. The expression levels of protein by immunohistochemistry results were similar to the results by Western blot. TUNEL staining showed that the apoptotic neurons were characterized by yellow or brown particle in the nucleus. The apoptotic index (AI) of neurons at 4 and 24 hours was significantly increased in HI group when compared with sham group (P<0.05), and the AI of neurons was significantly decreased in HI+Rg1 group when compared with HI group and HI+Rg1+U0126 group at 24 hours (P<0.05). CONCLUSIONS: Rg1 could enhance HIBD induced HIF-1alpha expression and inhibit activation of Caspase-3 by Erk1/2 signaling pathway, and play an anti-apoptotic role in neonatal rats with HIBD. PMID- 29786236 TI - [EFFECT OF RECOMBINANT CO-EXPRESSION ADENOVIRUS OF NERVE GROWTH FACTOR AND MYELIN ASSOCIATED GLYCOPROTEIN GENES ON RAT SCIATIC NERVE INJURY]. AB - OBJECTIVE: To construct recombinant adenovirus expressing nerve growth factor (NGF) and myelin associated glycoprotein (MAG) (Ad-NGF-MAG) and to investigate its effect on repair and regeneration of sciatic nerve injury in rats. METHODS: NGF and MAG gene sequences were cloned into shuttle plasmid pCA13 of adenovirus type 5. After packed in HEK293 cells, the recombinant Ad-NGF-MAG underwent sequence and identification. Thirty-two male Sprague Dawley rats were randomly divided into 4 groups (n=8): control group (normal control), adenovirus vector group (Ad group), Ad-NGF group, and Ad-NGF-MAG group. The sciatic nerve injury model was established by transection of the right sciatic nerve; then, the empty adenovirus vector, Ad-NGF, and Ad-NGF-MAG were injected into the gastrocnemius muscle of the affected limb at a dose of 1*108 PFU every other day for 3 times in Ad group, AdNGF group, and Ad-NGF-MAG group, respectively. The right sciatic nerve was exposed only, and then the incision was closed in the control group. The sciatic nerve function index (SFI) was measured, and neuro-electrophysiology was observed; mRNA and protein expressions of NGF and MAG were detected by RT-PCR and Western blot; and histological examination was performed at 31 days after operation. RESULTS: Recombinant adenovirus vectors of Ad-NGF and Ad-NGF-MAG were constructed successfully. All rats survived and incision healed by first intension. The SFI, nerve conduction velocity, evoked potential amplitude, and latent period of Ad-NGF-MAG group were significantly better than those of Ad group and Ad-NGF group (P<0.05). MAG mRNA and protein expressions of Ad-NGF-MAG group were the highest in all the groups (P<0.05). The expressions of NGF mRNA and protein increased in Ad-NGF group and AdNGF-MAG group when compared with control group and Ad group (P<0.05). Histological examination showed that the nerve had good continuity in control group; nerve fibers disarranged in Ad group; neurons connections formed in some nerve fibers of Ad-NGF group, but nerve fibers arrange disorderly; and the growth of the nerve were ordered and wellstructured in Ad-NGF-MAG group. CONCLUSIONS: Ad-NGF-MAG can effectively promote the growth of the nerve and inhibit the form of abnormal branches, facilitating the repair of sciatic nerve injury in rats. PMID- 29786235 TI - [NEUROPROTECTIVE EFFECTS OF MANGIFERIN ON ACUTE SPINAL CORD INJURY IN RATS AND ITS MECHANISM]. AB - OBJECTIVE: To investigate the protective effect of mangiferin on acute spinal cord injury (SCI) in rats and its mechanism. METHODS: Ninety Sprague Dawley rats were randomly divided into 5 groups, 18 rats in each group. SCI was induced by using the Allen's method (60 g/cm) at T9 level in the rats of groups B, C, D, and E; laminectomy was performed at T8-10 in group A. The rats were injected intraperitoneally with saline in groups A and B, and with mangiferin in groups C (10 mg/kg), D (25 mg/kg), and E (50 mg/kg) every day for 30 days. The survival condition of rats was observed after operation; at 24, 48, and 72 hours after operation, the motor function of the hind limb was evaluated by the Basso, Beattie, Bresnahan (BBB) scores. The spinal cord edema was assessed by measuring the water content in spinal cord tissues at 72 hours. Meanwhile, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were detected by ELISA; nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-6 were measured via ELISA at the same time. Caspase-3 and Caspase-9 were also detected by ELISA after mangiferin treatment for 30 days. The expressions of Bax and Bcl-2 proteins were detected by Western blot. Pathological changes of the spinal cord was observed by HE staining. And Caspase-3 protein expression was detected by immunohistochemical staining. RESULTS: All rats survived to the end of experiment. BBB scores of groups B, C, D, and E were significantly less than that of group A (P<0.05), and it showed an increase trend from groups B to E (P<0.05). The content of water of groups B, C, D, and E were significantly greater than that of group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). ELISA showed that the activities of MDA, NF-kappaB, TNF-alpha, IL 1beta, IL-6, Caspase-3, and Caspase-9 in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and they showed decrease trends from groups B to E (P<0.05). Meanwhile, the activities of CAT, SOD, and GSH in groups B, C, D, and E were significantly less than that in group A (P<0.05), and they showed increase trends from groups B to E (P<0.05). Western blot showed that the relative expression of Bax protein in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). Meanwhile, the relative expression of Bcl-2 protein in groups B, C, D, and E were significantly less than that in group A (P<0.05), and it showed an increase trend from groups B to E (P<0.05). Histological observation showed that the pathological changes in group B were accord with that in SCI, and the degree of necrosis in groups C, D, and E were significantly improved when compared with that in group B, and the effect was better in group E than group D, and group D than group C. Immunohistochemical staining showed that the absorbance (A) value of Caspase-3 in groups B, C, D, and E were significantly greater than that in group A (P<0.05), and it showed a decrease trend from groups B to E (P<0.05). CONCLUSIONS: Mangiferin has neuroprotective effects on acute SCI in rats by alleviating edema of spinal cord, inhibiting oxidative stress and inflammation response, and regulating the Bcl-2 and Bax pathway. PMID- 29786237 TI - [EFFECT OF alpha-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE]. AB - OBJECTIVE: To investigate the effect of alpha-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet. METHODS: Sixty male C57BL/6J mice weighting 200-300 g were randomly divided into model group (control group, n=15), alpha-lipoic acid-treated model group (n=15), miR 29b mimic group (n=15), and miR-29b mimic negative control group (NC group, n=15). All animals received intraperitoneal injection of streptozocin to establish the diabetic model. Then, a full thickness wound of 5 mm*2 mm in size was created at 4 weeks after modeling. All mice were administrated with high sugar-fat-diet. At the same day after modeling, alpha-lipoic acid-treated model group was continuously given intravenous injection of 100 mg/(kg.d) alpha-lipoic acid for 14 days; miR-29b mimic group and NC group received the tail intravenous injection of lentiviral vector for miR-29b mimic and miR-29b mimic negative control (a total of 2*107 TU), respectively, with the treatment of alpha-lipoic acid. The wound healing was observed and wound area was measured at 7 and 14 days. The wound tissues were harvested to detect the levels of superoxide dismutase (SOD) and glutathione (GSH) using xanthine oxidase method and 5, 5 dithiobis-2-nitrobenzoic acid staining method at 14 days. At the same day, 7, and 14 days after modeling, the relative miR-29b expression in wound tissues from control and alpha-lipoic acid-treated model groups was detected by real-time fluorescence quantitative PCR. RESULTS: All mice survived to the experiment end. The wound healing was faster in alpha-lipoic acid-treated group than control group. At 7 and 14 days, the relative wound area and miR-29b expression level were significantly lower, while the contents of SOD and GSH were significantly higher in alpha-lipoic acid-treated group than control group (P<0.05). In addition, miR-29b mimic group had significantly increased relative wound area and significantly decreased the contents of SOD and GSH when compared with NC group at 7 and 14 days (P<0.05). CONCLUSIONS: alpha-lipoic acid could inhibit oxidative stress and promote diabetic wound healing by suppressing expression of miR-29b in mice. PMID- 29786238 TI - [REGUL ATORY EFFECT OF SIMVASTATIN ON MIDDLE/L ATE STAGES OSTEOGENIC DIFFERENTIATION OF BONE MARROW MESENCHYMAL STEM CELLS VIA p38MAPK PATHWAY]. AB - OBJECTIVE: To investigate the regulatory effect of simvastatin on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) at middle/late stages by p38MAPK pathway under condition of osteoinductive environment. METHODS: The bone marrow of bilateral femur and tibia were harvested from 20 4-week-old female Sprague Dawley rats. BMSCs were isolated and cultured with whole bone marrow culture method; the second generation of cells were randomly divided into 5 groups: control group (complete medium, CM), simvastatin group (simvastatin medium, SIM), osteogenic induction group (osteogenic induction medium, OM), simvastatin and osteogenic induction group (simvastatin+osteogenic induction medium, OM+SIM), and blocker group (SB203580+simvastatin+osteogenic induction medium, OM+SIM+SB). MTT assay was used to detect the cell activity in CM group and SIM group at 2, 3, 4, 5, and 6 days, ELISA method to measure the content of alkaline phosphatase (ALP) in OM group and OM+SIM group at 7 and 14 days. The mRNA and protein expressions of osteocalcin (OCN) were detected by real-time quatitative PCR and Western blot after 1, 12, and 24 hours of osteogenic induction at 21 and 28 days. The protein expressions of phospho-p38 (p-p38) and p38 in OM group, OM+SIM group, and OM+SIM+SB group were detected by Western blot at the best induction time of simvastatin. RESULTS: MTT assay showed that no significant difference was found in absorbance (A) value between CM group and SIM group at each time point (P>0.05), indicating no effect of 1*10-7 mol/L simvastatin on cell viability. ELISA results showed that ALP content significantly increased in OM+SIM group when compared with OM group at 7 and 14 days; the ALP content was significantly higher at 7 days than 14 days in OM group and OM+SIM group (P<0.05). OCN mRNA and protein expressions at 12 hours were significantly higher than those at other time points in each group (P<0.05), and the expressions of OM+SIM group was significantly higher than those of OM group (P<0.05). The best induction time of simvastatin was 12 hours. At 12 hours after blocking intervention, the p-p38/p38 in OM+SIM+SB group was significantly lower than that in OM group and OM+SIM group (P<0.05), and the p-p38/p38 in OM+SIM group was significantly higher than that in OM group (P<0.05). CONCLUSIONS: Simvastatin can increase the mRNA and protein expression levels of OCN and the protein of p-p38 in osteogenic differentiation of BMSCs at middle/ late stages, and its best induction time is 12 hours. PMID- 29786239 TI - [RESEARCH PROGRESS OF SURGICAL SELECTION OF FUSION LEVELS FOR DEGENERATIVE SCOLIOSIS]. AB - OBJECTIVE: To summarize the progress of the surgical selection of fusion levels for degenerative scoliosis. METHODS: The domestic and foreign related literature about degenerative scoliosis, including clinical features, classification, surgical treatment, and the fused segment, was summarized. RESULTS: Degenerative scoliosis is very complicated. Short segment fusion and long segment fusion are the main surgical types. The long segment fusion is better in terms of reconstructing the stability of spine; however, it has more related complications. The short segment fusion has been used widely in clinical, but it causes degenerative disease easily. W/AL value can be used to direct the selection of short or long segment fusion for degenerative scoliosis. CONCLUSIONS: The key to success surgery is choosing reasonable fused segment. Now there is no unified selection standard. With more knowledge about degenerative scoliosis, greater development can be expected in the future. PMID- 29786240 TI - [Technical summary and modified instruments of free vascularized fibular grafting for osteonecrosis of femoral head]. AB - Objective: To summarize retrospectively the clinical technology of repairing osteonecrosis of femoral head (ONFH) by free vascularized fibular grafting (FVFG), and the value of modified instruments in operation. Methods: Between March 2011 and January 2013, 35 patients with ONFH (47 hips) who underwent FVFG with modified instruments. There were 24 males (32 hips) and 11 females (15 hips), aged 34 years on average (range, 22-43 years). The unilateral hip was involved in 23 cases and the bilateral hips in 12 cases. The disease duration ranged from 5 to 9 months (mean, 7 months). Based on etiology, 25 hips were classified as alcohol ONFH, 12 hips as corticosteroids ONFH, 3 hips as trauma ONFH, and 7 hips as idiopathic ONFH. According to the Association Research Circulation Osseous(ARCO) stage, 3 hips were rated as stage I, 39 hips as stage II, and 5 hips as stage III on the X-ray films. The preoperative Harris score was 58.2+/-6.1. Results: The time to get fibula was 15-35 minutes (mean, 25 minutes). The operation time was 90-200 minutes (mean, 130 minutes), and the blood loss during operation was 150-500 mL (mean, 270 mL). All the patients achieved primary healing of incision, without complication of infection or deep vein thrombosis. All 35 patients were followed up 12-42 months, with an average of 28 months. The Harris score at final follow-up was 87.3+/-5.7, showing significant difference when compared with preoperative score ( t=102.038, P=0.000). Radiographic results at final follow-up showed good position of fibula; and necrosis was improved in 9 hips, had no changes in 36 hips, and aggravated in 2 hips. Conclusion: FVFG for ONFH can improve hip function effectively, and modified instruments can improve operation efficiency. PMID- 29786241 TI - [Effectiveness of distal femoral osteotomy assisted by three-dimensional printing technology for correction of valgus knee with osteoarthritis]. AB - Objective: To evaluate the effectiveness of distal femoral osteotomy aided by three-dimensional (3D) printing cutting block for correction of vaglus knee with osteoarthritis. Methods: Between January 2014 and January 2016, 12 patients (15 knees) with vaglus deformity and lateral osteoarhritis underwent medial closing wedge distal femoral osteotomy. There were 5 males and 7 females, aged 30-60 years (mean, 43.8 years). The mean disease duration was 6.6 years (range, 1-12 years). The unilateral knee was involved in 9 cases and bilateral knees in 3 cases. According to Koshino's staging system, 1 knee was classified as stage I, 9 knees as stage II, and 5 knees as stage III. The X-ray films of bilateral lower extremities showed that the femorotibial angle (FTA) and anatomical lateral distal femoral angle (aLDFA) were (160.40+/-2.69) degrees and (64.20+/-2.11) degrees respectively. Mimics software was used to design and print the cutting block by 3D printing technique. During operation, the best location of distal femoral osteotomy was determined according to the cutting block. After osteotomy, internal fixation was performed using a steel plate and screws. Results: All incisions healed primarily; no complication of infection or deep vein thrombosis was observed. All patients were followed up 6-18 month (mean, 12.2 months). At 6 months after operation, the hospital for special surgery (HSS) score for knee was significantly improved to 89.07+/-2.49 when compared with preoperative score (65.27+/-1.49, t=-28.31, P=0.00); the results were excellent in 10 knees, good in 4 knees, and fair in 1 knee with an excellent and good rate of 93.3%. The bony union time was 2.9-4.8 months (mean, 3.3 months). Bone delayed union occurred in 1 case (1 knee). The postoperative FTA and aLDFA were (174.00+/-1.41) degrees and (81.87+/-1.06) degrees respectively, showing significant differences when compared with preoperative ones ( t=-18.26, P=0.00; t=-25.19, P=0.00). The percentage of medial tibial plateau in whole tibial plateau was 49.78%+/-0.59%, showing no significant difference when compared with intraoperative measurement (49.82%+/-0.77%, t=0.14, P=0.89). Conclusion: 3D printing cutting block can greatly improve the accuracy of distal femoral osteotomy, and ensure better effectiveness for correction of vaglus knee with osteoarthritis. PMID- 29786242 TI - [Effect of Jumbo cups for total hip arthroplasty revision on femoral offset and hip center of rotation]. AB - Objective: To investigate the change of the femoral offset and hip center of rotation (COR) after using Jumbo cups in total hip arthroplasty (THA) revision. Methods: The clinical data of 23 patients who underwent THA revision using Jumbo cups between January 2010 and May 2015 were retrospectively analyzed. Morselized bone graft was performed on 8 cases, morselized bone graft combined with structural bone graft on 10 cases. There were 10 males and 13 females, aged 65.4 years on average (range, 51-77 years). The disease duration was 1-24 years (mean, 8.57 years). The reasons for revision included aseptic loosening in 21 cases and periprosthetic infection in 2 cases. The Harris hip score and visual analogue scale (VAS) were 43.04+/-5.05 and 5.70+/-0.97 before operation respectively. According to the Paprosky acetabular defect classification, there were 5 cases of type I, 5 cases of type II A, 3 cases of type II B, 6 cases of type II C, and 4 cases of type III A. The X-ray films showed that the femoral offset was (40.65+/ 4.09) mm for normal side and was (44.04+/-5.08) mm for affected side at preoperation, showing significant difference ( t=4.098, P=0.000). Ten patients underwent femoral offset reconstruction (43.48%) but 13 patients did not (56.52%) before operation. The COR was reconstructed in 10 cases (43.48%); COR elevation was observed in 11 cases (47.83%), and COR decline in 2 cases (8.69%) before operation. Results: Primary healing of incision was obtained in all patients, with no complication of infection, vascular injury, deep vein thrombosis, dislocation of the joint, or fracture around prosthesis. All the patients were followed up 12-76 months (mean, 22.48 months). The Harris hip score and VAS were 82.09+/-4.53 and 0.74+/-0.62 at 1 year after operation respectively, showing significant differences when compared with preoperative scores ( t=37.831, P=0.000; t=22.318, P=0.000). The X-ray films showed that the femoral offset was (43.87+/-3.57) mm for affected side at 1 year after operation, showing no significant difference when compared with preoperative one ( t=0.250, P=0.805), but significant difference was found between affected side and normal side ( t=5.591, P=0.000). The femoral offset was restored in 16 patients (69.57%) and was not restored in 7 patients (30.43%) after operation. The COR was restored in 15 patients (65.22%) and was not restored in 8 patients (34.78%). Conclusion: Using Jumbo cups or combined with morselized or structural bone graft is effective in restoring hip COR and femoral offset at the maximum limit in THA revision, with good short-term outcome and improved stability of acetabular prosthesis. PMID- 29786243 TI - [Mid- and long-term effectiveness and failure causes analysis of large-head metal on-metal total hip arthroplasty]. AB - Objective: To explore the effectiveness and failure causes of large-head metal-on metal total hip arthroplasty (large-head MoM THA). Methods: Between March 2007 and May 2010, 159 patients (183 hips) underwent large-head MoM THA, and the clinical data were analyzed. There were 50 females (54 hips) and 109 males (129 hips) with an average age of 50 years (range, 20-78 years). Single hip was involved in 135 cases (left hip in 69 cases and right hip in 66 cases) and double hips in 24 cases. The causes included femoral head necrosis in 74 cases (93 hips), Legg-Calve-Perthes in 1 case (1 hip), osteoarthritis in 18 cases (19 hips), developmental dysplasia of the hip in 17 cases (18 hips), osteoarthritis after hip septic infection in 8 cases (8 hips), traumatic arthritis of the hip in 6 cases (6 hips), femoral neck fracture in 17 cases (17 hips), ankylosing spondylitis in 8 cases (11 hips), rheumatoid arthritis of hip in 9 cases (9 hips), and adult onset Still's disease in 1 case (1 hip). Before operation, visual analogue scale (VAS) was 6.59+/-0.87; Harris score was 45.99+/-8.07. Results: Healing of incisions by first intention was achieved, and no operative complication occurred. The patients were followed up 1.2-8.2 years (mean, 6.1 years). Implant failure was observed in 15 cases (17 hips), and the 5-year survival rate of large-head MoM THA was 91.80% (168/183). The causes of implant failure after THA were inflammatory pseudotumor in 4 cases (4 hips), acetabular aseptic loosening in 3 cases (3 hips), osteolysis in 4 cases (5 hips), acetabular aseptic loosening combined with inflammatory pseudotumor in 3 cases (3 hips), and functional disused in 1 case (2 hips). Of them, 9 cases (11 hips) did not receive revision surgery for various reasons, while 6 cases (6 hips) underwent revision surgery at 1.2-5.4 years (mean 3.7 years) after large-head MoM THA. At last follow-up, VAS and Harris score were 1.72+/-1.48 and 81.37+/-10.75 respectively, showing significant differences when compared with preoperative scores ( t= 35.547, P=0.000; t=33.823, P=0.000). The function was excellent in 44 hips, good in 89 hips, fair in 33 hips, and poor in 17 hips. Conclusion: Large-head MoM THA has a high revision rate during mid- and long-term follow-up because of inflammatory pseudotumor, acetabular aseptic loosening, and osteolysis. Early revision can effectively improve the function of the hip and improve patients'quality of life. PMID- 29786244 TI - [Effectiveness of arthroscopic debridement and release for post-traumatic arthritis of subtalar joint]. AB - Objective: To evaluate the effectiveness of arthroscopic debridement and release for post-traumatic arthritis of subtalar joint. Methods: Between January 2011 and December 2014, 14 cases of post-traumatic arthritis of the subtalar joint underwent arthroscopic debridement and release, and the clinical data were retrospectively analyzed. All patients were male, aged 42 years on average (range, 32-62 years). Calcaneus fracture was caused by falling from height; 8 cases received conservative treatment and the other 6 cases received open reduction and internal fixation. The mean interval from injury to operation was 3.4 years (range, 2-7 years). The arthroscopic debridement and release were performed through lateral portals. The injury degree of articular cartilage was classified as grade 3 in 4 cases and grade 4 in 10 cases based on Outerbridge rating. The degree of pain was assessed by visual analogue scale (VAS) and the function of joint was assessed by the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Scale. Results: All incisions healed by first intention and no complication occurred. The follow-up time was 18 months. Pain was relieved obviously; VAS was significantly decreased to postoperative 3.8+/-0.9 at 18 months from preoperative 7.7+/-1.2 ( t=9.728, P=0.000), and AOFAS Ankle Hindfoot Scale was significantly increased to postoperative 59.1+/-8.8 from preoperative 37.6+/-8.2 ( t=6.688, P=0.000). During follow-up, no patient was given arthrodesis and no worsened sign was found on the postoperative CT and MRI. Conclusion: Arthroscopic debridement and release for post-traumatic arthritis of the subtalar joint can relieve clinical symptoms and delay subtalar arthrodesis. PMID- 29786246 TI - [Tissue flap combined with sequential bone lengthening technique for repairing severe soft tissue and bone defects of lower extremity after burn injury]. AB - Objective: To investigate the effectiveness of tissue flap grafting and sequential bone lengthening for repairing severe soft tissue and bone defects of the lower extremity after burn injury. Methods: Between January 2010 and December 2015, 11 cases of large segmental bone and soft tissue defects in the leg were treated. There were 10 males and 1 female, with a mean age of 28 years (range, 19 37 years). The causes included traffic accident in 8 cases, high voltage electric burn in 2 cases, CO poisoning burn in 1 case. The time from injury to admission was 3-14 days (mean, 6.5 days). The bone defect length was 8-18 cm (mean,14 cm); the skin soft tissue defect ranged from 13 cm * 8 cm to 25 cm * 19 cm. After complete removal of necrotic tissue and lesions of the femur or the tibia, the tissue flaps were used to repair soft tissue defect of the lower extremity in one stage operation; bone defect was treated by Orthofix single side external fixation or Ilizarov ring external fixation in two-stage operation. Results: Eleven flaps survived completely, primary healing of incision was obtained in the others except for 1 patient who had necrotic bone infection, which was cured after removing necrosed femoral bone and filling with antibiotic bone cement spacer. During bone lengthening, pin tract infection occurred in 1 patient, and infection was controlled after dressing change. Bone lengthening ranged from 8 to 18 cm, with an average of 14 cm. After prolonged extension, the external fixator was retained for 4-12 months (mean, 6.5 months). All bone defects were repaired with bone healing time of 12-22 months (mean, 17 months). All patients were followed up 8-24 months (mean, 15 months). No vascular and neurological complication occurred during operation; no osteomyelitis or re-fracture occurred after operation, and the recovery of the lower extremity function was good. Conclusion: Tissue flap grafting combined with bone lengthening is an effective method to repair severe bone and soft tissue defects of lower extremity. PMID- 29786245 TI - [Treatment of traumatic ulnar styloid impaction syndrome by Sauve-Kapandji procedure]. AB - Objective: To evaluate the effectiveness of Sauve-Kapandji procedure in the treatment of traumatic ulnar styloid impaction syndrome. Methods: Between June 2010 and January 2013, 12 patients with traumatic ulnar styloid impaction syndrome were treated by Sauve-Kapandji procedure. There were 4 men and 8 women, with an average age of 58.9 years (range, 50-69 years). The disease was caused by traffic accident in 1 case, and by falling from height in 11 cases. All patients had dislocation of the distal radioulnar joint, and 7 patients also had old fractures of the distal radius. The main clinical symptoms were pain and limited activity of the wrist joint, and the disease duration was 2-4 months (mean, 3.5 months). The visual analogue scale (VAS) was 6.2+/-1.4. The clinical outcomes were assessed by VAS, range of motion (ROM) of the wrist, grip strength, Evans score, and X-ray film of wrist joint during follow-up. Results: All patients obtained healing of incision by first intention and were followed up 37-73 months (mean, 58.4 months); no complication of infection, blood vessel injury, or nerves injury occurred. VAS was 1.2+/-1.0 at the final follow-up, showing significant difference when compared with preoperative one ( t=9.950, P=0.000). The ROM of the affected wrist joint in flexion, extension, ulnar deviation, forearm pronation and supination were improved, but the ROM of the affected side were significantly less than those of normal side ( P<0.05). No significant difference was found in the grip strength and Evans score between the affected side and normal side ( t=-0.885, P=0.386; t=-1.969, P=0.062). According to Evans scores, the results were excellent in 8 cases, good in 3 cases, and fair in 1 case, with an excellent and good rate of 91.7%. Postoperative radiographs showed bony healing in all patients, with the average healing time of 3.5 months (range, 3-6 months). The instability of proximal ulna occurred in 3 cases. Conclusion: Sauve Kapandji procedure is a reliable remedy method for traumatic ulnar styloid impaction syndrome, with favorable improvement in wrist pain and forearm rotation. However, the surgical indications for Sauve-Kapandji procedure should be strictly controlled. PMID- 29786247 TI - [Biomechanical assessment of newly-designed proximal femoral medial buttress plate for treatment of reverse oblique femoral intertrochanteric fracture]. AB - Objective: To evaluate the biomechanical properties of proximal femoral medial buttress plate (PFMBP) for fixing the reverse oblique intertrochanteric fractures by comparing with proximal femoral locking compression plate (PFLCP) and proximal femoral nail antirotation (PFNA). Methods: Eighteen synthetic femoral bone models (Synbone) were divided into 3 groups (group PFLCP, group PFNA, and group PFMBP), 6 models in each group; an AO 31-A3.1 reverse oblique femoral intertrochanteric fracture was made based on the same criterion. After being fixed and embeded, the axial load testing, torsion testing, and axial load-to-failure testing were performed on each model. The axial displacement of different loads, torque of different torsion angles, and failure load of each model were recorded, and the stiffness of axial load and torsion were calculated. Results: The axial stiffness in groups PFLCP, PFNA, and PFMBP were (109.42+/-30.14), (119.13+/-29.14), and (162.05+/-22.05) N/mm respectively, showing significant differences between groups ( P<0.05). There were significant differences in torque between different torsion angles in the same group, as well as in the torque between groups at the same torsional angle ( P<0.05). The torsion stiffness in groups PFLCP, PFNA, and PFMBP were (1.45+/-0.44), (1.10+/-0.13), and (1.36+/-0.32) N.mm/deg respectively; there were significant differences when compared groups PFLCP and PFMBP with group PFNA ( P<0.05), but no significant difference was found between group PFLCP and group PFMBP ( P>0.05). The failure loads of groups PFLCP, PFNA, and PFMBP were (1 408.88+/- 0.17), (1 696.56+/-0.52), and (2 154.65+/-0.10) N respectively, showing significant differences between groups ( P<0.05). Conclusion: The newly designed PFMBP is better than PFNA and PFLCP in axial load stiffness and torsion stiffness for fixing reverse oblique intertrochanteric fracture by biomechanical test, indicating that reconstruction of medial stability is a key element for unstable intertrochanteric fracture. PMID- 29786248 TI - [Biomechanical evaluation of the first carpometacarpal joint stability by using different reconstruction methods]. AB - Objective: To study the biomechanical differences of the first carpometacarpal joint stability by using different reconstruction methods so as to provide theoretical basis for the clinical choice of reconstruction method. Methods: The upper limb specimens were selected from 12 fresh adult cadavers, which had no fracture, bone disease, dislocation of wrist joint, deformity, degeneration, or ligament injury on the anteroposterior and lateral X-ray films. The specimens were randomly divided into 5 groups: normal group, injury group, palmar carpometacarpal ligaments reconstruction group, dorsal carpometacarpal ligaments reconstruction group, and palmar and dorsal carpometacarpal ligaments reconstruction group. Three normal specimens were used as normal group, and then were made of the first carpometacarpal joint dislocation models (injury group); after the first carpometacarpal joint dislocation was established in the other 9 specimens; the volar ligament, dorsal ligament, and volar-dorsal ligaments were reconstructed with Eaton-Little method, Yin Weitian method, and the above two methods in 3 construction groups. The biomechanical test was done to obtain the load-displacement curve and to calculate the elastic modulus. Results: During biomechanical test, ligament rupture and loosening of Kirschner wire occurred in 1 case of injury group and palmar carpometacarpal ligaments reconstruction group; no slipping was observed. The elastic modulus values were (11.61+/-0.20), (5.39+/ 0.12), (6.33+/-0.10), (7.12+/-0.08), and (8.30+/-0.10) MPa in normal group, injury group, palmar carpometacarpal ligaments reconstruction group, dorsal carpometacarpal ligaments reconstruction group, and palmar and dorsal carpometacarpal ligaments reconstruction group respectively, showing significant differences among groups ( P<0.05). Conclusion: Volar ligament reconstruction, dorsal ligament reconstruction, and volar-dorsal ligament reconstruction all can greatly improve the stability of the first carpometacarpal joint. And the effect of volar-dorsal ligament reconstruction is the best, but the stability can not restore to normal. PMID- 29786249 TI - [Biomechanical effect of anteromedial coronoid facet fracture and lateral collateral ligament complex injury on posteromedial rotational stability of elbow]. AB - Objective: To investigate the effect of anteromedial coronoid facet fracture and lateral collateral ligament complex (LCLC) injury on the posteromedial rotational stability of the elbow joint. Methods: The double elbows were obtained from 4 fresh adult male cadaveric specimens. Complete elbow joint (group A, n=8), simple LCLC injury (group B, n=4), simple anteromedial coronoid facet fracture (group C, n=4), and LCLC injury combined with anteromedial coronoid facet fracture (group D, n=8). The torque value was calculated according to the load-displacement curve. Results: There was no complete dislocation of the elbow during the experiment. The torque values of groups A, B, C, and D were (10.286+/-0.166), (5.775+/-0.124), (6.566+/-0.139), and (3.004+/-0.063) N.m respectively, showing significant differences between groups ( P<0.05). Conclusion: Simple LCLC injury, simple anteromedial coronoid facet fracture, and combined both injury will affect the posteromedial rotational stability of the elbow. PMID- 29786250 TI - [Effect of staphylococcal lipoteichoic acid on differentiation of RAW264.7 cells into osteoclasts]. AB - Objective: To investigate the effect of staphylococcal lipoteichoic acid (LTA-sa) on RAW264.7 cells differentiation into osteoclasts. Methods: RAW264.7 cells were cultured with LTA-sa of 100 ng/mL (group A), LTA-sa of 200 ng/mL (group B), LTA sa of 400 ng/mL (group C), receptor activator of nuclear factor kappaB (NF kappaB) ligand (RANKL) of 100 ng/mL as positive control (group D), and equal volume of PBS as blank control (group E) respectively for 5 days. And then, tartrate resistant acid phosphatase staining (TRAP) was used to detect the formation of osteoclast-like cells, Image-Pro Plus 6.0 software to measure the areas of bone resorption pits in Corning Osteo Assay Surface (COAS) wells, and MTT assay to observe the proliferation activity of RAW264.7 cells in group A, B, C, and E. Results: After cultured for 5 days, the formation of osteoclast-like cells and bone resorption pits were observed in all groups. The number of osteoclast-like cells and the area of bone resorption pits in groups A, B, C, and D were more than those in group E. And with the increased concentration of LTA sa, the indexes in groups A, B, and C increased gradually, but were lower than those in group D, and differences were significant between groups ( P<0.05). At 5 days after culture, there was no significant difference in absorbance value among the experimental groups (groups A, B, C, and E) ( P>0.05). Conclusion: LTA-sa has promoting effect on RAW264.7 cells differentiation into osteoclasts. PMID- 29786251 TI - [Effectiveness comparison between two operations in treatment of unstable type Kummell's disease]. AB - Objective: To compare the effectiveness between short segmental fixation combined with vertebroplasty (SSF+VP) and short segmental pedicle screw fixation combined with bone graft (SSF+BG) in the treatment of unstable type Kummell's disease so as to provide a reference for the selection of the surgical method. Methods: Between March 2013 and February 2015, 48 patients with unstable type Kummell's disease who were in accordance with the inclusive criteria were included in the study. SSF+VP were used in 25 cases (SSF+VP group) and SSF+BG in 23 cases (SSF+BG group). There was no significant difference in gender, age, disease duration, bone mineral density, fracture segment, and preoperative visual analogue scale (VAS), Oswestry disability index (ODI), and kyphotic Cobb angle between 2 groups ( P>0.05). The operation time and complications related to operation were recorded; the effectiveness was evaluated by VAS, ODI, and kyphotic Cobb angle. Results: The operation time was (107.7+/-18.8) minutes in SSF+VP group and was (113.7+/-22.4) minutes in SSF+BG group, showing no significant difference between 2 groups ( t=-1.045, P=0.302). Bone cement leakage occurred in 6 cases of SSF+VP group, and incision delayed healing occurred in 1 case of SSF+BG group. All patients achieved bone graft fusion on X-ray films. The bone graft fusion time was (15.1+/-1.3) weeks in SSF+VP group and (15.7+/-1.8) weeks in SSF+BG group, showing no significant difference between 2 groups ( t=-1.361, P=0.180). The VAS, ODI, and kyphotic Cobb angle at immediate after operation and at last follow-up were significantly lower than preoperative ones ( P<0.05). The VAS, ODI, and kyphotic Cobb angle had no significant difference between at immediate and at last follow-up in SSF+VP group ( P>0.05). In SSF+BG group, VAS at last follow-up was significantly lower than that at immediate after operation ( P<0.05), but no significant difference was found in kyphotic Cobb angle and ODI ( P>0.05). SSF+VP group was significantly better than SSF+BG group in VAS at immediate after operation ( P<0.05), but SSF+BG group was significantly better than SSF+VP group at last follow-up ( P<0.05). There was no significant difference in kyphotic Cobb angle and ODI between 2 groups at immediate after operation and at last follow-up ( P>0.05). Conclusion: SSF+BG can achieve satisfactory effectiveness in the treatment of unstable type Kummell's disease, and it has the advantages of good bony healing, obvious improvement of pain, and low complication incidence when compared with SSF+VP. PMID- 29786253 TI - [Application of improved injecting tube in percutaneous kyphoplasty through unipedicular puncturing]. AB - Objective: To research the feasibility and effectiveness of percutaneous kyphoplasty (PKP) by improved injecting tube through unipedicular puncturing. Methods: Between January 2012 and Junuary 2016, 60 cases (68 vertebrae) of osteoporotic vertebral compression fractures (OVCF) were treated. PKP was performed through unipedicular puncturing with routine injecting tube in 30 cases (34 vertebrae, routine group), and with improved injecting tube in 30 cases (34 vertebrae, improved group). There was no significant difference in age, gender, disease duration, fracture level, preoperative visual analogue scale (VAS), or vertebral height between 2 groups ( P>0.05). The operation time, the volume of bone cement injected, preoperative and postoperative VAS, and preoperative and postoperative vertebral height, and postoperative distribution coefficient of bone cement were recorded and compared between 2 groups. Results: Good healing of puncture points was achieved in 2 groups after PKP, and no serious complication occurred. There was no significant difference in operation time and the volum of bone cement injected between 2 groups ( t=0.851, P=0.399; t=1.672, P=0.101). Bone cement leakage was observed in 2 cases of 2 groups respectively. The distribution coefficient of bone cement in routine group was significantly less than that in improved group ( t=13.049, P=0.000). All patients were followed up 12-36 months (mean, 19 months). The postoperative VAS and vertebral height were significantly improved when compared with preoperative ones in 2 groups ( P<0.05), but there was no significant difference in VAS between at 2 days after operation and at last follow-up, in vertebral height between at 2 days after operation and at 1 year after operation, and between 2 groups after operation ( P>0.05). X-ray films showed vertebral compression fractures in 6 cases of routine group and in 1 case of improved group during follow-up. Conclusion: PKP by improved injecting tube through unipedicular puncturing can improve the distribution of bone cement, restore the height and strength of vertebral body, and reduce the incidence of re fracture. PMID- 29786252 TI - [Percutaneous transforaminal endoscopic discectomy combined with Coflex interspinous process dynamic reconstruction system in treatment of youth lumbar disc herniation]. AB - Objective: To evaluate the effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) combined with Coflex interspinous process dynamic reconstruction system for the treatment of youth lumbar disc herniation (LDH). Methods: The clinical data of 52 patients with LDH treated by PTED combined with Coflex were retrospectively analyzed between February 2013 and March 2015. The involved segments were L 4, 5 in 30 cases and L 5, S 1 in 22 cases. In 30 patients at L 4, 5 level, there were 18 males and 12 females with an average age of 25 years (range, 18-34 years) and a mean disease duration of 10 months (range, 6-16 months). In 22 patients at L 5, S 1 level, there were 10 males and 12 females with an average age of 25.5 years (range, 19-32 years) and a mean disease duration of 12 months (range, 6-18 months). The operation time and intraoperative blood loss were recorded. Oswestry disability index (ODI) and Japanese Orthpoaedic Association (JOA) score were used for effectiveness assessment. Radiograpic indexes were calculated on X-ray films before operation and final follow-up, including ventral intervertebral space height (VH), dorsal intervertebral space height (DH), intervertebral foramen height (IFH), the range of motion (ROM) of involved segment, and the ROM of upper adjacent segment. Results: The operations were successfully completed in 52 patients. The operation time and intraoperative blood loss were (89.7+/-16.5) minutes and (42.7+/-11.3) mL in patients at L 4, 5 level, and were (94.6+/-18.2) minutes and (47.6+/-13.4) mL in patients at L 5, S 1 level. Incisions healed by first intention. All patients were followed up 12-18 months (mean,16 months) in patients at L 4, 5 level and 12-20 months (mean, 17 months) in patients at L 5, S 1 level. At final follow-up, ODI, and JOA score were significantly improved when compared with preoperative ones in all patients ( P<0.05). X-ray films showed no complication of Coflex loosening, spinous process fracture, or articular process fracture occurred. At final follow-up, VH, DH, and IFH were significantly improved when compared with preoperative ones in all patients ( P<0.05), and the ROM of involved segment was significantly reduced compared with preoperative one ( P<0.05), but the ROM of upper adjacent segment showed no significant difference when compared with preoperative one ( P>0.05). Conclusion: PTED combined with Coflex is a safe and effective minimally invasive surgery in treating youth LDH; however, it still needs further clinical studies. PMID- 29786254 TI - [Clinical application of accurate placement of lumbar pedicle screws using three dimensional printing navigational templates under Quadrant system]. AB - Objective: To explore the feasibility and the effectiveness of the accurate placement of lumbar pedicle screws using three-dimensional (3D) printing navigational templates in Quadrant minimally invasive system. Methods: The L 1-5 spines of 12 adult cadavers were scanned using CT. The 3D models of the lumbar spines were established. The screw trajectory was designed to pass through the central axis of the pedicle by using Mimics software. The navigational template was designed and 3D-printed according to the bony surface where the soft tissues could be removed. The placed screws were scanned using CT to create the 3D model again after operation. The 3D models of the designed trajectory and the placed screws were registered to evaluate the placed screws coincidence rate. Between November 2014 and November 2015, 31 patients with lumbar instability accepted surgery assisted with 3D-printing navigation module under Quadrant minimally invasive system. There were 14 males and 17 females, aged from 42 to 60 years, with an average of 45.2 years. The disease duration was 6-13 months (mean, 8.8 months). Single segment was involved in 15 cases, two segments in 13 cases, and three segments in 3 cases. Preoperative visual analogue scale (VAS) was 7.59+/ 1.04; Oswestry disability index (ODI) was 76.21+/-5.82; and the Japanese Orthopaedic Association (JOA) score was 9.21+/-1.64. Results: A total of 120 screws were placed in 12 cadavers specimens. The coincidence rate of placed screw was 100%. A total of 162 screws were implanted in 31 patients. The operation time was 65-147 minutes (mean, 102.23 minutes); the intraoperative blood loss was 50 116 mL (mean, 78.20 mL); and the intraoperative radiation exposure time was 8-54 seconds (mean, 42 seconds). At 3-7 days after operation, CT showed that the coincidence rate of the placed screws was 98.15% (159/162). At 4 weeks after operation, VAS, ODI, and JOA score were 2.24+/-0.80, 29.17+/-2.50, and 23.43+/ 1.14 respectively, showing significant differences when compared with preoperative ones ( t=14.842, P=0.006; t=36.927, P=0.002; t=-36.031, P=0.001). Thirty-one patients were followed up 8-24 months (mean, 18.7 months). All incision healed by first intention, and no complication occurred. During the follow-up, X-ray film and CT showed that pedicle screw was accurately placed without loosening or breakage, and with good fusion of intervertebral bone graft. Conclusion: 3D-printing navigational templates in Quadrant minimally invasive system can help lumbar surgery gain minimal invasion, less radiation, and accurate placement. PMID- 29786255 TI - [Imaging and biomechanics researches of reconstructing lumbosacral stability after L 5 vertebrectomy via anterolateral approach]. AB - Objective: To investigate the feasibility of anterolateral approach for L 5 vertebral resection, bone grafting, and screw rod fixation by imaging and biomechanics researches. Methods: Twenty formalized adult cadavers (12 males and 8 females) were randomly divided into 2 groups; L 5 vertebral resection, bone graft, and screw rod fixation was performed on 10 specimens by using anterolateral approach (experimental group), and on the other 10 specimens by combined anterior and posterior approach. CT scanning and three-dimensional reconstruction were performed in the experimental group; preoperative maximal safe entry angle and depth of screws and intraoperative actual entry angle and depth of screws were measured; the sacral screw position was observed after operation. The biomechanical test was done in 2 groups. Results: Twenty specimens smoothly underwent L 5 excision and reconstruction. CT scan showed that there was no significant difference in maximal safe entry angle and depth of screws between males and females in experimental group before operation ( P>0.05); the maximal safe entry angle and depth were 51.93 degrees and 47.88 mm for anterior screw, and were 37.04 degrees and 46.28 mm for posterior screw. After operation, depth of the sacral anterior and posterior screws were appropriate, which did not pierce into the spinal canal. The biomechanical test results indicated that the flexion, extension, and lateral flexion displacements, and vertical compression stiffness showed no significant difference between 2 groups ( P>0.05). Conclusion: For L 5 lesions not invading posterior column, to use L 5 vertebral resection, bone graft, and screw rod fixation by anterolateral approach is a safe and feasible method to reconstruct lumbosacral stability, with the advantages of no changing posture, less operation time and incision, and prevention of bone graft shift, but effectiveness need further be identified. PMID- 29786256 TI - [Effectiveness of combined Pregabalin and Celecoxib for treatment of neuropathic pain after percutaneous endoscopic lumbar discectomy]. AB - Objective: To investigate the effectiveness of combined Pregabalin and Celecoxib for neuropathic pain after percutaneous endoscopic lumbar discectomy. Methods: Between January and June 2014, 178 patients with lumbar disc herniation underwent percutaneous endoscopic interlaminar discectomy (PEID). Ninety patients who met the inclusion criteria were recruited in this study. Every case in group A was recruited to match its counterpart in group B and group C according to gender, disease duration, herniated level, smoking history, preoperative Leeds assessment of neuropathic symptoms and signs (LANSS), and Oswestry disability index (ODI). Nine patients were excluded due to incomplete study or loss of follow-up. In each group, 27 cases were included in the final analysis. There was no significant difference in gender, age, height, body mass index, herniated level, disease duration, smoking history, preoperative LANSS, ODI, and visual analogue scale (VAS) between groups ( P>0.05). All patients of 3 groups received oral administration of Celecoxib from preoperative 3rd day to postoperative 14th day. Pregabalin was taken orally from preoperative 3rd day to postoperative 14th day in group A, and from postoperative 1st to 14th day in group B. Adverse drug reactions were observed during medication. The LANSS score and VAS score in rest state and active state were conducted before operation and at 1 day, 1 month, and 3 months after operation. ODI was conducted before operation and at 1, 3 months after operation. The number of neuropathic pain cases was recorded, and the effectiveness was evaluated by modified Macnab criteria at 3 months after operation. Results: During period of increasing Pregabalin dose, 1 patient of group A suffered severe dizziness, and 1 patient of group B suffered sleepiness, who were eliminated from this research. Another 2 cases (1 case of group A and 1 case of group C) suffered dry mouth, and 1 case of group B suffered muscle weakness. At 1 day after operation, the LANSS score and VAS in rest state and active state of group A were significantly lower than those of groups B and C ( P<0.05). At 1 month after operation, the LANSS score, ODI, and VAS in rest state and active state of group A and group B were significantly lower than those of group C ( P<0.05). At 3 months after operation, the LANSS score, ODI, and VAS in active state of group A and group B were significantly lower than those of group C ( P<0.05). There was no significant difference in the above indicators at the other time points between groups ( P>0.05). Neuropathic pain occurred at 3 months after operation in 1 case (3.7%) of group A and 6 cases (22.2%) of group C, showing significant differences in incidence of neuropathy pain between groups A, B and group C ( P<0.05), but no significant difference was found between group A and group B ( P>0.05). The excellent and good rate of modified Macnab criteria was 92.6% in group A, was 88.9% in group B, and was 85.2% in group C at 3 months after operation, showing no significant difference between groups ( P>0.05). Conclusion: Combined use of Pregabalin and Celecoxib during perioperative period can reduce postoperative pain and incidence of postoperative neuropathic pain. Preoperative oral Pregabalin can reduce the incidence of acute postoperative neuropathic pain. PMID- 29786257 TI - [Clinical application of free thoracoacromial artery perforator flap in reconstruction of tongue and mouth floor defects after resection of tongue carcinoma]. AB - Objective: To investigate the clinical outcome of free thoracoacromial artery perforator (TAAP) flap in the reconstruction of tongue and mouth floor defects after radical resection of tongue carcinoma. Methods: Between May 2010 and February 2015, 11 cases of tongue carcinoma underwent radical resection and reconstruction of tongue and mouth floor defects with free TAAP flaps. The locations of tongue carcinoma were the lingual margin in 7 cases, the ventral tongue in 2 cases, and the mouth floor in 2 cases. According to Union for International Cancer Control (UICC) TNM stage, 3 cases were classified as T 4N 0M 0, 3 cases as T 4N lM 0, 2 cases as T 3N 1M 0, 2 cases as T 3N 2M 0, and 1 case as T 3N 0M 0. The disease duration ranged from 3 to 28 months, 10.6 months on average. The tumor size ranged from 6.0 cm*3 cm to 10 cm*5 cm. The TAAP flap ranged from 7.0 cm*4.0 cm to 11.0 cm*5.5 cm in size, and 0.6-1.2 cm (0.8 cm on average) in thickness, with a pedicle length of 6.8-9.9 cm (7.2 cm on average). Results: All 11 flaps survived, the donor site was closed directly and healed primarily in all cases. The patients were followed up 12-24 months (17.2 months on average). The reconstructed tongue had satisfactory appearance and good functions of swallowing and language. No local recurrence was observed during follow-up. Only linear scar was left at the donor site, and the function of pectoralis major muscle was normal. Conclusion: The TAAP flap is an ideal choice in the reconstruction of tongue defect after resection of tongue carcinoma, which has good texture, appearance, and function results. PMID- 29786258 TI - [Clinical application of changeable cross-leg style sural neurovascular flap in repairing contralateral fairly large soft tissue defect on dorsum of forefoot]. AB - Objective: To explore the effectiveness of changeable cross-leg style sural neurovascular flap in repairing contralateral fairly large soft tissue defects on dorsum of forefoot. Methods: Between June 2006 and June 2015, 12 patients with fairly large soft tissue defect on dorsum of forefoot were treated. There were 8 males and 4 females, with an average age of 35.6 years (range, 18-57 years). Defects were caused by traffic accident injury in 4 cases, machine crush injury in 3 cases, and heavy object crush injury in 3 cases, with a median disease duration of 11 days (range, 5 hours to 28 days) in the 10 cases; the defect cause was atrophic scar in 2 cases, with disease duration of 2 years and 3 years respectively. The wound size of soft tissue ranged from 6.2 cm*4.1 cm to 11.5 cm*7.4 cm; combined injuries included tendon exposure in all cases and bone exposure in 6 cases. The changeable cross-leg style sural neurovascular flaps were used to repair defects. The width and length of flap pedicle were increased. The cross-leg position was maintained with the elastic net bandage. The size of flaps was 16 cm*7 cm to 21 cm*11 cm, with a pedicle of 8-16 cm in length and 5-6 cm in width. Results: After operation, 10 flaps survived, and wound healed by first intention. Extravasated blood occurred at the flap edge in 2 cases and was cured after symptomatic treatment. No pressure sore occurred. All patients were followed up 3-24 months (mean, 7 months). The appearance and function of the affected legs were good, and the flaps had soft texture and normal color. Conclusion: Changeable cross-leg style sural neurovascular flap can achieve good effectiveness in repairing fairly large soft tissue defect on dorsum of forefoot. Some drawbacks of single cross-leg style can be avoided. PMID- 29786259 TI - [Application of vascular repair and reconstruction in surgical treatment of superior vena cava syndrome caused by thoracic tumor]. AB - Objective: To summarize the clinical experience of vascular repair and reconstruction for treating superior vena cava syndrome (SVCS) caused by thoracic tumor. Methods: Between October 2008 and June 2016, 26 patients with thoracic tumor and SVCS were admitted. There were 18 males and 8 females, aged from 27 to 70 years (mean, 45.9 years). Tumor was typed as B1-B3 thymoma in 13 cases, thymic carcinoma in 6 cases, large B-cell lymphoma in 3 cases, T lymphocytic lymphoma in 1 case, malignant teratoma in 1 case, right lung squamous cell carcinoma in 1 case, and carcinoid in 1 case. The tumor diameter ranged from 8 to 15 cm with an average of 10 cm. The patients had different degrees of neck, face, and upper extremity edema, jugular vein distention, and chest wall collateral venous filling. The superior vena cava pressure was 2.45-5.39 kPa. After excision of tumor and invading superior vena cava, 7 patients underwent superior vena cava reconstruction and 19 patients underwent artificial vascular replacement. Results: There was no perioperative death, and the symptoms of superior vena cava obstruction were eliminated. Postoperative pulmonary infection, respiratory muscle weakness, and right chylothorax occurred in 4 cases, 1 case, and 1 case respectively. Twenty-four patients were followed up 2-92 months (mean, 37 months), and 2 patients failed to be followed up. At 1, 3, and 5 years, the survival rate was 83.3% (20/24), 41.7% (10/24), and 25% (6/24), respectively. In 6 patients with 5-year survival, there were 1 case of type B1 thymoma, 3 cases of type B3 thymoma, and 2 cases of large B-cell lymphoma. Conclusion: For preoperative evaluation of SVCS caused by resectable thoracic tumors, vascular repair and recons-truction technique can be used to quickly and effectively relieve the clinical symptoms and improve the quality of life. PMID- 29786260 TI - [Mechanism of lipolytic and smooth effects of D980-nm laser treatment on skin tissue in rats]. AB - Objective: To determine the efficacy of D980-nm laser in dissolving fat and renewing skin, and to explore the clinical application of D980-nm laser in reconstruction of photodamaged skin. Methods: Eighteen 12-14 month-old male Sprague-Dawley rats, weighing 400-450 g, were randomly divided into 3 groups ( n=6). The rat skin at the left side was exposed to D980-nm laser irradiation at a density of 20 J/cm 2, a power of 8 W, a pulse width of 20 ms, and a pulse frequency of 40 Hz for 1 time (group A), 2 times of 5-minute interval (group B), and 3 times of 5-minute interval (group C) as a treatment course, for 4 treatment courses with an interval of 1 week; the other side of the skin was not treated as the control groups (groups A1, B1, and C1, respectively). After 8 weeks, the skin was harvested for HE staining and immunohistochemical staining to observe the structure changes of skin, to measure the dermal thickness, to count the number of fibroblasts, and detect the expressions of transforming growth factor beta 1 (TGF-beta 1) and basic fibroblast growth factor (bFGF). Results: Compared with groups A1, B1, and C1, the skin structure was significantly improved in groups A, B, and C. After D980-nm laser irradiation, the number of fat cells decreased; local angiogenesis was observed; the total number of fibroblasts and fibers increased; the collagen fiber had large diameter, and arranged closely and regularly; the dermal thickness and the number of the fibroblasts increased; and the expressions of TGF-beta 1 and bFGF were significantly enhanced, showing significant differences ( P<0.05). With increased D980-nm laser irradiation times, the above indexes increased, showing significant differences between group C and groups A, B ( P<0.05). Conclusion: D980-nm laser treatment has lipolytic and tender effect on the skin, and the frequency of the treatment is an important factor in skin renewal. PMID- 29786262 TI - [Progress of anatomic research and clinical application of facial artery perforator flap]. AB - Objective: To summarize the present status and progress of the anatomy researches and clinical application of the facial artery perforator flap (FAPF). Methods: The relative researches focused on the anatomy researches and clinical application of FAPF were extensively reviewed, analyzed, and summarized. Results: The facial artery perforator (FAP) has constant anatomy. There are more facial artery perforators in the perioral region, and each FAP has two accompanying veins. Distinguished by inferior mandibular border, the upper and the lower flaps both are used for reconstruction of defects on the face. The most widely-used upper flap was FAPF, which is excellent choice of defects in mid-face. Additionally, angular artery perforator flap and lateral nasal artery perforator flap are becoming more and more popular. While submental artery perforator flap, whose pedicle locates under inferior mandibular border, is most used for reconstruction of lower face. FAPF for face defect repair can achieve good outcomes of function and appearance in clinical application. Conclusion: Based on multiple advantages of good aesthetics and function outcomes, high survival rate, flexible design, and simple operation, FAPF is an optimal choice for defect repair of perioral region and nasal ala. However, Further study is needed to determine whether retaining tissue around the pedicle will affect vein reflux of the flap. PMID- 29786261 TI - [Effects of interleukin 10 gene modified bone marrow mesenchymal stem cells on expression of inflammatory cytokines and neuronal apoptosis in rats after cerebral ischemia reperfusion injury]. AB - Objective: To explore the effects of interleukin 10 (IL-10) gene modified bone marrow mesenchymal stem cells (BMSCs) on the expression of inflammatory cytokines and neuronal apoptosis in rats after cerebral ischemia reperfusion injury. Methods: BMSCs were cultured by whole bone marrow adherence screening method. The properties of BMSCs were identified by immunocytochemical methods. BMSCs at passage 3 were transfected with recombinant adenovirus IL-10 gene (AdIL-10 BMSCs). The model of middle cerebral artery occlusion was made in 40 adult male Sprague Dawley rats by thread embolism method. The rats were randomly divided into 4 groups ( n=10). At 3 hours after modelling, the rats of groups A, B, C, and D received tail intravenous injection of 1 mL L-DMEM medium containing 10% FBS, 61.78 ng IL-10, 1 mL BMSCs suspension (2*10 6 cells/mL), and 1 mL AdIL-10 BMSCs cell suspension (2*10 6 cells/mL), respectively. The cells were labelled with BrdU before cell transplantation in groups C and D. At 7 days after reperfusion, the brain tissue was harvested to detect the expression of OX42 by immunohistochemical assay, to determine the concentration of tumor necrosis factor alpha (TNF-alpha) and IL-1beta by ELISA, and to detect the apoptosis by TUNEL assay. BrdU labelled cells were observed by immunofluorescence staining in groups C and D. Results: BrdU labelled positive cells with green fluorescence were observed in the brain tissue of groups C and D, which mainly distributed in the striatum, cerebral cortex, and subcortex around the infarction area. The number of OX42 positive cells was significantly less in groups B, C, and D than group A ( P<0.05), and in group D than groups B and C ( P<0.05). Compared with the other 3 groups, the contents of TNF-alpha and IL-1beta significantly decreased in group D ( P<0.05). TUNEL assay showed that the apoptotic cells (TUNEL positive cells) were mainly seen in the striatum and fronto parietal subcortical tissues (equivalent to ischemic penumbra). The number of TUNEL positive cells in group D was significantly less than that in groups A, B, and C ( P<0.05). Conclusion: AdIL-10-BMSCs can inhibit secretion of TNF-alpha and IL 1beta from microglial cells and inhibit the nerve cell apoptosis around infarct brain tissue, which might contribute to its protective role upon cerebral ischemia reperfusion injury. PMID- 29786263 TI - [EFFECT AND MECHANISM RESEARCH OF HYDROCHLORIC PROPRANOLOL CREAM ON WOUND HEALING IN DIABETIC MICE]. AB - OBJECTIVE: To investigate the effect of hydrochloric propranolol cream and its possible mechanism on wound healing in diabetic mice. METHODS: Eighteen 8-week old BKS.Cg-Dock7m+/+Leprdb/JNju diabetic mice were randomly divided into control group (n=9) and experimental group (n=9). After full-thickness dermal wounds (0.6?cm in diameter) was made, wounds were treated with cream containing hydrochloric propranolol (experimental group) or not containing hydrochloric propranolol (control group) at 2, 5, 7, 10, 14, and 17 days. At 2, 5, 7, 10, 14, 17, and 21?days, wound healing was observed, and healing rate was calculated; HE staining, Masson staining, and toluidine?blue staining were used to observe wound re-epithelialization, collagen fibers, and mast cells distribution. Western blot was applied to detect the expressions of interleukin 1beta (IL-1beta) and angiogenin 2 (Ang2) in wound tissue. RESULTS: Wounds healed in 2 groups, but the wounds healing rate of experimental group was significantly higher than that of control group at other time points (P < 0.05) except 21 days (P > 0.05). The histological observation showed that re-epithelialization rate was higher in experimental group than control group, there were less mast cells in the wound. The experimental group was lower than control group in IL-1beta expression at 2, 5, 7, 14, 17, and 21 days and in Ang2 expression at 2, 5, 7, 10, 14, 17, and 21 days. CONCLUSIONS: Hydrochloric?propranolol cream can promote wound healing in diabetic mice, which?potential?mechanism?is?that propranolol can promote epidermal cell proliferation, reduce inflammation, and benefit angiogenesis. PMID- 29786264 TI - [APPLICATION OF DIRECT LATERAL INTERBODY FUSION FOR LUMBAR DEGENERATIVE DISEASES]. AB - OBJECTIVE: To investigate the effectiveness of direct lateral interbody fusion (DLIF) for lumbar degenerative diseases. METHODS: A retrospective study was done on 25 cases of lumbar degenerative diseases treated with DLIF between May 2013 and May 2014. There were 15 males and 10 females with an average age of 61.4 years (range, 36-78 years), including 14 cases of lumbar disc herniation, 2 cases of degenerative lumbar scoliosis, 3 cases of lumbar spondylolisthesis, and 6 cases of lumbar instability with spinal stenosis. The disease duration was 8 months to 20 years (mean, 5.7 years). The involved segments included L4, 5 in 10 cases, L3, 4 in 6 cases, L2, 3 in 2 cases, L2-4 in 2 cases, L3-5 in 3 cases, and L2-5 in 2 cases. The operation time, intraoperative bleeding volume, postoperative hospitalization time, and complications were recorded. The visual analogue scale (VAS) and Oswestry disability index (ODI) criteria were used to assess the effectiveness; X-ray film and CT were used to evaluate the bone fusion. RESULTS: The mean operation time was 105?minutes (range, 85-155 minutes), and mean intraoperative bleeding volume was 158 mL (range, 80-300?mL). The postoperative hospitalization time was 2-5 days (mean, 3.2 days). All incisions healed by first intension. There was no complication of wound infection, vascular injuries, or intraoperative visceral injuries. All cases were followed up 24.6 months on average (range, 18-30 months). Four cases had iliopsoas weakness, 5 cases had iliopsoas weakness and anterior thigh hypoesthesia, which disappeared within 6 months after operation. No retrograde ejaculation, Cage displacement, or loosening was found after operation. Full bony fusion was observed in 20 segments and partial bony fusion in 12 segments. The mean bony fusion time was 10.8 months (mean, 6-18 months). The height of intervertebral space was significantly increased to (11.98+/-1.20)?mm at 2 days after operation and to (11.80+/-1.33) mm at last follow-up from preoperative (6.20+/-0.88) mm (P < 0.05), but no significant difference was found between at 2 days and last follow-up (P > 0.05). At last follow-up, VAS score was significantly decreased to 3.43+/-0.53 from preoperative 8.26+/-0.49 (t=26.275, P=0.000), and ODI was significantly decreased to 15.41%+/-3.91% from preoperative 40.80%+/-3.10% (t=22.902, P=0.000). CONCLUSIONS: DLIF is a safe and effective treatment for lumbar degenerative diseases, which has the advantages of less tissue damage, less blood loss, and fast rehabilitation. PMID- 29786265 TI - [CLINICAL STUDY ON MODIFIED LAMINOPLASTY WITH POSTERIOR COLUMN RESERVATION FOR TREATMENT OF LUMBAR SPINAL STENOSIS]. AB - OBJECTIVE: To investigate the technique and effectiveness of modified laminoplasty for lumbar spinal stenosis (LSS) and to explore the application value of modified laminoplasty in maintaining the stability of the spine by comparing with the conventional laminectomy. METHODS: Fifty-six patients with LSS were included between June 2012 and July 2013, and they were divided into 2 groups: 27 patients underwent modified laminoplasty in group A, and 29 patients received conventional laminectomy in group B. There was no significant difference in sex, age, disease duration, narrow segment, visual analogue scale (VAS) score of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, and walking tolerance between 2 groups (P > 0.05). The postoperative VAS score of low back pain and leg pain, JOA score, walking tolerance, X-ray film, and CT were used to evaluate the clinical results. RESULTS: Dural tear occurred in 2?cases of group A and 1 case of group B and were repaired during operation. All incisions primarily healed without infection. The patients were followed up 24-31 months (mean, 24.7 months) in group A, and 24-37 months (mean, 26.2 months) in group B. The bone healing time was 6-12 months (mean, 9 months) in group A. CT showed healing at the junction of spinous process and vertebral plate in group A at 12 months after operation; new scar in varying degre es was observed in group B. At last follow-up, lumbar spondylolisthesis and instability occurred in 4?and 2 cases of group B respectively, and received re-operation. The change value of slip distance was (0.27+/-0.23) mm in group A and was (0.83+/-1.22) mm in group B, showing significant difference (t=-2.405, P=0.023). The postoperative JOA score, VAS score, and walking tolerance were significantly improved when compared with preoperative ones in 2 groups (P < 0.05).?At?last follow-up, group A was better than group B in VAS score of low back pain (P < 0.05), but no significant?difference?was?found in the other indexes between 2 groups (P > 0.05). CONCLUSIONS: The modified laminoplasty?is better than the conventional laminectomy in relieving low back pain and maintaining the stability of the lumbar spine. PMID- 29786266 TI - [EFFECTIVENESS OF PREPERITONEAL HERNIORRHAPHY WITH Ultrapro Plug MESH FOR UMBILICAL HERNIA REPAIR IN ADULTS]. AB - OBJECTIVE: To explore the effectiveness of preperitoneal herniorrhaphy with Ultrapro Plug (UPP) mesh for umbilical hernia repair in adults. METHODS: Between September 2011 and June 2015, 71 patients with umbilical hernia underwent preperitoneal herniorrhaphy with UPP mesh. There were 26 males and 45 females, aged 19-92 years (mean, 54.3 years). The disease duration was 45 days to 30 years (median, 18 months). Umbilical hernia was diagnosed through physical examination, ultrasound, and other relevant auxiliary examination. According to American Society of Anesthesiologists (ASA) classification, 12 cases were rated as grade I, 34 cases as grade II, 21 cases as grade III, and 4?cases as grade IV. The operation time, postoperative hospitalization time, complication, and recurrence were recorded. RESULTS: The diameter of hernia ring ranged 0.5-3.0 cm (mean, 1.8 cm). There was no vessel or intestine injury. The operation time was 12-35 minutes (mean, 22.4 minutes); postoperative hospitalization time was 12-48 hours (mean, 16.3 hours). Fat liquefaction of incision occurred in 2 cases, and primary healing of incision was obtained in the other cases. Sixty-nine patients were followed up 8-51 months (median, 28 months). Hernia recurrence and patch infection occurred in 1 case respectively during follow-up. No postoperative foreign body sensation and chronic pain occurred. CONCLUSIONS: Repairing umbilical hernia in adults with UPP mesh should be safe and reliable, because it has the advantages of short operation time, short hospital stay, less complication, and lower incidence of recurrence. PMID- 29786267 TI - [SHORT-TERM EFFECTIVENESS OF PERCUTANEOUS PEDICLE SCREW GUIDED WITH PHOTOELECTRIC NAVIGATION FOR THORACOLUMBAR FRACTURES]. AB - OBJECTIVE: To investigate the short-term effectiveness of percutaneous pedicle screw (PPS) guided with photoelectric navigation for thoracolumbar fractures. METHODS: Between May 2013 and June 2015, the clinical data of 39 patients with thoracolumbar fractures in accordance with the selection criteria were retrospectively analyzed. The patients were divided into photoelectric navigation PPS group (trial group, 20 cases) and C-arm X-ray guidance PPS group (control group, 19 cases). There was no significant difference in gender, age, injury cause, fracture vertebrae, AO classification, operation time after injury, visual analogue scale (VAS) score, and vertebral compression ratio (VCR) between 2 groups (P > 0.05). The operation time, bleeding amount, perspective times, VAS score, and one-time success rate (OSR) of screw placement were recorded; VCR and endplate-screw angle (ESA) were measured; and pedicle-screw relationship (PSR) was assessed by Ringel's method in radiographic result. RESULTS: Differences in operation time and bleeding amount were not significant between 2 groups (P > 0.05); perspective times of control group was significantly more than t hat of trial group (t=-15.658, P=0.000). The OSR of trial group (95.60%, 87/91) was significantly better than that of control group (86.75%, 72/83) (chi2=4.323, P=0.038). The patients were followed up 6-11 months (mean, 7.6 months) in trial group, and 7-11 months (mean, 7.8 months) in control group. No neurovascular complications associated with screw insertion occurred. Difference was not significant in VAS score at 7 days and 6 months after operation between 2 groups (P > 0.05), but VAS scores at 7 days and 6 months were significantly improved when compared with preoperative score in 2 groups (P < 0.05), and significant difference in VAS score was shown between at 7 days and 6 months in 2 groups (P < 0.05). VCR of trial group and control group were significantly improved to 94.75%+/-5.10% and 92.40%+/-5.09% at 6 months after operation from preoperative 71.97%+/-5.66% and 73.50%+/-5.97% (t=11.865, P=0.000; t=11.359, P=0.000), but there was no significant difference between 2 groups (t=1.442, P=0.158). ESA of trial group and control group were (1.82+/-1.13) degrees and (3.36+/-2.43) degrees at 6 months after operation, showing significant difference (t=5.421, P=0.000). At 6 months after operation, according to PSR classification, 83 screws rated as grade I, 6 as grade II, and 2 as grade III, and excellent and good rate of screw replacement was 97.80% in trial group; 54 screws were rated as grade I, 19 as grade II, 7 as grade III, and 3 as grade IV, and excellent and good rate of screw replacement was 87.95% in control group; difference was significant between 2?groups (chi2=18.347, P=0.000). CONCLUSIONS: Application of photoelectric navigation can guide screws placement by the two-dimensional multi pl ane dynamic image, has better accuracy of screws position in thoracolumbar fractures, reduces the introperative X-ray perspective times, maintains good reduction of vertebral body, and achieves satisfactory effectiveness. PMID- 29786268 TI - [ENDOSCOPIC CALCANEOPLASTY FOR Haglund's DEFORMITY WITH HINDFOOT PAIN]. AB - OBJECTIVE: To analyze the effectiveness of endoscopic calcaneoplasty (ECP) for treating hindfoot pain in patients with Haglund's deformity by comparing with conservative treatment. METHODS: According to the included standard, 64 hindfoot pain patients (77 feet) with Haglund's deformity treated between January 2007 and October 2013 were enrolled. Based on the patient's sports habit, 39 patients (49 feet) who had no requirement on sports were given conservative treatment (control group) and 25 patients (28 feet) who had stable sports habit were given ECP (ECP group). There was no significant difference in age, gender, disease duration, disease side, Fowler-Philip angle, and preoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score between 2 groups (P > 0.05). RESULTS: The patients were followed up 16-44 months (mean, 33.7 months) in ECP group, and 12-40 months (mean, 37.5 months) in control group. In control group, the syndrome in 34 cases (43 feet) disappeared after 2 weeks; pain was improved in 5?cases (6 feet), and pain disappeared at 3 weeks after orthesis immobilization; hindfoot pain recurred in 24 cases (30 feet) during following-up, 11 cases (13 feet) underwent ECP after 1 year. In ECP group, all incisions healed by first intention without nerve injury; no edema or pain was observed during follow-up. AOFAS ankle hindfoot score was significantly improved in 2 groups when compared with score at pre-treatment (P < 0.05). With time, AOFAS ankle-hindfoot score gradually decreased in control group, but it gradually increased in ECP group. The AOFAS ankle-hindfoot score of ECP group was significantly higher than that of control group after treatment (P < 0.05). According to Ogilvie-Harris score system at 12 months, the results were excellent in 9 cases, good in 12 cases, and poor in 4 cases, with the excellent and good rate of 84.00% in ECP group; and the results were excellent in 8 cases, good in 14 cases, and poor in 17 cases, with the excellent and good rate of 56.41% in control group. There was significant difference in the excellent and good rate between 2 groups (Z=-2.194, P=0.028). CONCLUSIONS: Under the premise of strict control of surgical indications, the ECP can bring satisfactory effectiveness for treatment of hindfoot pain in patients with Haglund's deformity. PMID- 29786269 TI - [PREPARATION AND BIOCOMPATIBILITY OF IN SITU CROSSLINKING HYALURONIC ACID HYDROGEL]. AB - OBJECTIVE: To fabricate in situ crosslinking hyaluronic acid hydrogel and evaluate its biocompatibility in vitro. METHODS: The acrylic acid chloride and polyethylene glycol were added to prepare crosslinking agent polyethylene glycol acrylate (PEGDA), and the molecular structure of PEGDA was analyzed by Flourier transformation infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy. Hyaluronic acid hydrogel was chemically modified to prepare hyaluronic acid thiolation (HA-SH). And the degree of HA-SH was analyzed qualitatively and quantitatively by Ellman method. HA-SH solution in concentrations (W/V) of 0.5%, 1.0%, and 1.5% and PEGDA solution in concentrations (W/V) of 2%, 4%, and 6% were prepared with PBS. The two solutions were mixed in different ratios, and in situ crosslinking hyaluronic acid hydrogel was obtained; the crosslinking time was recorded. The cellular toxicity of in situ crosslinking hyaluronic acid hydrogel (1.5% HA-SH and 4% PEGDA mixed) was tested by L929 cells. Meanwhile, the biocompatibility of hydrogel was tested by co-cultured with human bone mesenchymal stem cells (hBMSCs). RESULTS: Flourier transformation infrared spectroscopy showed that most hydroxyl groups were replaced by acrylate groups; 1H nuclear magnetic resonance spectroscopy showed 3 characteristic peaks of hydrogen representing acrylate and olefinic bond at 5-7 ppm. The thiolation yield of HA-SH was 65.4%. In situ crosslinking time of hyaluronic acid hydrogel was 2 to 70 minutes in the PEGDA concentrations of 2%-6% and HA-SH concentrations of 0.5%-1.5%. The hyaluronic acid hydrogel appeared to be transparent. The toxicity grade of leaching solution of hydrogel was grade 1. hBMSCs grew well and distributed evenly in hydrogel with a very high viability. CONCLUSIONS: In situ crosslinking hyaluronic acid hydrogel has low cytotoxicity, good biocompatibility, and controllable crosslinking time, so it could be used as a potential tissue engineered scaffold or repairing material for tissue regeneration. PMID- 29786270 TI - [APPLICATION OF NASOLABIAL FLAP AND EAR CARTILAGE IN REPAIRING DEFECTS AFTER NASAL ALA BASAL CELL CARCINOMA RESECTION]. AB - OBJECTIVE: To investigate the effectiveness of nasolabial flap and ear cartilage in repairing defects after nasal ala basal cell carcinoma resection. METHODS: Between January 2012 and August 2014, 8 patients with nasal ala basal cell carcinoma underwent tumor resection?and defect repair with nasolabial flap and ear cartilage. Among the 8 patients, 5 were male and 3 were female, with an average age of 65 years (range, 45-76 years). The left side and right side were involved in 3 cases and 5 cases respectively. Carcinoma confirmed by pathological examination in all patients. The time between first biopsy and resection was 7-14 days (mean, 10 days). The defect ranged from 1.5 cm*1.5 cm to 2.0 cm*1.5?cm after tumor resection, and the size of nasolabial flaps ranged from 4.0 cm*1.5 cm to 5.0 cm*2.0 cm. The operations of cutting off the pedicle and thinning skin flap were performed at 6 months after first operation. RESULTS: All flaps survived. Incisions healed by first intention, and no related complication occurred. No carcinoma recurred after cutting off the pedicle. All patients were followed up for 6 months. All patients were satisfied with the nasal contour, symmetrical projection of the alar dome, and no obvious scar. CONCLUSIONS: Nasolabial flap transfer and ear cartilage transplant method not only can repair the nasal ala defects, but also can avoid obvious scar and obtain good nasal ala contour profile. The shortcoming is that patients have to receive two operations. PMID- 29786271 TI - [EFFECTIVENESS OF MODIFIED Ishiguro TECHNIQUE WITH STRENGTHENING PRESSURE IN TREATMENT OF BONY MALLET FINGERS]. AB - OBJECTIVE: To investigate the effectiveness of modified Ishiguro technique with strengthening pressure in the treatment of bony mallet finger by comparing with the traditional Ishiguro technique. METHODS: Between May 2013 and May 2015, 31 cases of bony mallet finger were treated with traditional Ishiguro technique in 16 cases (control group) and with modified Ishiguro technique in 15 cases (improved group, the two Kirschner wires were bound, which were used to fix the distal interphalangeal joint and blocking avulsion fracture block in the classical Ishiguro technique, and play a continuous elastic compression). Difference was not significant in gender, age, cause of injury, injury finger, and the time from injury to operation between 2 groups (P > 0.05). RESULTS: The wound healing was delayed in 2 cases of the control group and 1 case of the improved group, and the other patients obtained healing by first intension. The follow-up time was 8-23 months (mean, 11 months) in the improved group and was 9 24 months (mean, 12 months) in the control group. Bending deformation of the Kirschner wire occurred in 2 cases of the control group, obvious separation was found between fracture fragment and the distal phalanx; after manual reduction, brace was used to fix, and distal interphalangeal arthritis occurred during follow-up. The fracture healing time was (6.8+/-0.8) weeks in the control group, and was (5.7+/-1.5) weeks in the improved group. There was significant difference in the healing time between 2 groups (t=-2.439, P=0.021). At last follow-up, according to Crawford criteria, the results were excellent in 9 cases, good in 4 cases, fair in 2 cases, and poor in 1 case with an excellent and good rate of 81.25% in the control group; the results were excellent in 10 cases, good in 3 cases, and fair in 2 case with an excellent and good rate of 86.67% in the improved group. There was no significant difference in excellent and good rate between 2 groups (Z=-0.636, P=0.525). CONCLUSIONS: Compared with traditional Ishiguro technique, the modified Ishiguro technique with strengthening pressure in treatment of bony mallet finger can facilitate the fracture healing, reduce Kirschner wire loosening and deformation, and decrease the rates of operation failure and complications. PMID- 29786272 TI - [EFFECT OF BLOOD MICROENVIRONMENT OF RATS WITH HEPATIC FIBROSIS ON DIFFERENTIATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS INTO HEPATOCYTES AND ITS MECHANISMS]. AB - OBJECTIVE: To investigate the effect of blood microenvironment of rats with hepatic fibrosis on differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes and its mechanisms. METHODS: Eighteen male adult Sprague Dawley rats [weighing, (200+/-20) g] were used, liver fibrosis was induced in 12 rats by repeated intraperitoneal injections of thioacetamide. The serum was separated after successful model preparation, and the serum of 6 normal rats was collected. ELISA assay was used to detect the concentrations of epidermal growth factor (EGF), hepatocyte growth factor (HGF), oncostatin M (OSM), and basic fibroblastic growth factor (bFGF). Passage 3 HUCMSCs were divided into 3 groups: cells were cultured for 7 days in DMEM/F12 containing 10% fetal bovine serum and 5?mL/ L serum from rats with hepatic fibrosis (group A), in DMEM/F12 containing 10% fetal bovine serum and 5 mL/ L serum from normal rats (group B), and in DMEM/F12 containing 10% fetal bovine serum (group C). The morphological changes of the cells were observed. The expressions of alpha fetoprotein (AFP) and cytokeratin 18 (CK18) were detected by immunofluorescence. The protein levels of albumin (ALB), tryptophan 2, 3-dioxygenase (TPH2), and CYP3A4 and MAPK/ERK signal pathway protein (P-ERK) were detected using Western blot. The content of blood urea nitrogen (BUN) was measured by diacetyl m onoxime method. RESULTS: HE staining showed that the liver tissue of rats was in accordance with the change of fibrosis, indicating successful model preparation. In serum of normal rats and rats with hepatic fibrosis, the concentrations of EGF were (21.42+/-0.32) pg/mL and (17.57+/-0.31) pg/mL respectively, showing significant difference (t=14.989, P=0.000); the concentrations of OSM were (129.96+/-0.65) pg/mL and (98.44+/-1.32) pg/mL respectively, showing significant difference (t=37.172, P=0.000); the concentrations of HGF were below the detection limit and (1.03+/-0.12)?ng/ mL respectively; and the concentrations of bFGF were lower than the detection limit in both groups. No morphological changes of cells were observed in both groups at 7 days, and there was no significant difference between groups. At 7 days after culture, the cells in group A could express human hepatocyte biomarkers of AFP, CK18 and hepatocyte-specific-function proteins of ALB, TPH2, and CYP3 A4 while cells in groups B and C did not. Western blot showed that cells in each group could express P-ERK protein. The relative level of P-ERK protein in group A was significantly higher than that in groups B and C (P < 0.05), but no significant difference was found between groups B and C (P > 0.05). The BUN concentration of group A [(0.74+/-0.07)?mmol/ L] was significantly higher than that of groups B [(0.40+/-0.04)?mmol/ L] and C [(0.38+/ 0.04) mmol/L] (P < 0.05), but no significant difference was shown between groups B and C (P > 0.05). CONCLUSIONS: Under the condition of hepatic fibrosis, the level of HGF will increase while EGF and OSM will decrease. The formed blood microenvironment?will activate MAPK/ERK signal pathway in HUCMSCs, induce them differentiate into hepatocytes. PMID- 29786273 TI - [RESEARCH PROGRESS OF IN VIVO TWO-PHOTON IMAGING IN SPINAL CORD]. AB - OBJECTIVE: To review the in vivo imaging research progress of two-photon microscopy (TPM) in spinal cord. METHODS: The recent literature concerning in vivo two-photon imaging of axon, microglia, and calcium in transgenic mice spinal cord was extensively consulted and reviewed. RESULTS: In vivo two-photon imaging of spinal cord provide dynamic information about axonal degeneration and regeneration, microglial accumulation, and calcium influx after spinal cord injury. CONCLUSIONS: TPM in vivo imaging study on spinal cord will provide theoretical foundation for pathophysiologic process of spinal cord injury. PMID- 29786274 TI - [EFFICACY OF BIOACTIVE GLASS AND ALLOGENIC BONE IN REPAIR OF BONE DEFECT AFTER BENIGN BONE TUMOR CURETTAGE]. AB - OBJECTIVE: To compare the healing process and clinical results of bioactive glass and allogenic bone in the repair of bone defects after benign bone tumor curettage. METHODS: Between November 2011 and December 2012, 20 patients with benign bone tumor received bioactive glass and allogenic bone for repair of bone defects after benign bone tumor curettage. There were 17 males and 3 females, aged 9-68 years (median, 18.5 years). The mean course of disease was 3.3 months (range, 1-9 months). Pathological examination revealed that there were 7 cases of chondroblastoma, 5 cases of bone cyst, 2 cases of non-ossifying fibroma, 2 cases of enchondroma, 1 case of vascular tumor of bone, 1 case of lipoma of bone, 1 case of osteoid osteoma, and 1 case of chondromyxoid fibroma. The lesion located at the femur in 5 cases, at the tibia in 11 cases, at the humerus in 1 case, at the calcaneus in 2 cases, and at the talus in 1 case. The bioactive glass and allogenic cancellous bone were implanted in the cavity at the same time. The Musculoskeletal Tumor Society (MSTS) function evaluation score was used for evaluation of postoperative limb function. According to the imaging and clinical benefit, the healing processes of two kinds of implants were evaluated. The healing rate and healing time were compared. The distribution of the bioactive glass was divided into two layers: the layer close to host bone and the layer close to allogenic bone. The bone ingrowth time and bone resorption time in different layers were evaluated and compared. RESULTS: All cases were followed up 12-42 months (mean, 34.5 months). All incisions healed by first intention. There were no complications of wound infection or deep infection, rejection, nonunion of bone, fracture at bone graft site, and collapsing of articular surface. There was no tumor recurrence during follow-up. The mean MSTS functional score was 29.5 (range, 28-30) at last follow-up. Complete healing was observed in 11 cases and healing in 9 cases. The healing rates of two kinds of implants were both 100%. The healing time of bioactive glass and allogenic bone was (4.7+/-1.3) months and (5.2+/-1.6) months, respectively, showing no significant difference (t=-1.240, P=0.244). The bone ingrowth time and the bone absorption time were (3.6+/-0.9) months and (3.7+/-1.0) months in the layer close to host bone and were (4.2+/ 1.3) months and (4.2+/-1.3) months in the layer close to allogenic bone, all showing no significant difference (t=1.785, P=0.097; t=1.476, P=0.172). CONCLUSIONS: For the repair of bone defects after benign bone tumor curettage, bioactive glass can achieve satisfactory healing result and has good safety. PMID- 29786275 TI - [EFFICACY COMPARISON OF RECONSTRUCTION BELT AND RECONSTRUCTION PLATE FOR COMPLICATED ACETABULAR FRACTURE BY COMBINED ANTERIOR AND POSTERIOR APPROACHES]. AB - OBJECTIVE: To explore the advantage of reconstruction belt for treating complicated acetabular fracture by combined anterior and posterior approaches through the comparison with reconstruction plate. METHODS: A retrospective analysis was made on the clinical data of 39 patients with acetabular fractures who met the selection criteria. After open reduction by combined anterior and posterior approaches was performed, fracture was fixed by reconstruction belt in 20 cases (trial group), and by reconstruction plate in 19 cases (control group). There was no significant difference in gender, age, cause of injury, time from injury to hospital, type of fracture, and preoperative visual analogue scale (VAS) score between 2 groups (P > 0.05). The number of plate shaping, plate shaping time, operation time, bleeding amount, perspective times, VAS score, modified Merled'Aubigne-Postel hip score, and related complications were recorded and compared. According to Matta standard, the fracture displacement was measured to evaluate the fracture reduction and fracture healing. RESULTS: The number of plate shaping, plate shaping time, operation time, bleeding amount, and perspective times in the trial group were significantly less than those in the control group (P < 0.05). The patients were followed up 12-29 months (mean, 21.1 months) in the trial group, and 12-27 months (mean, 20.5?months) in the control group. The VAS score was significantly lower at 7 days and 6 months after operation than at pre-operation, and at 6 months than at 7 days in 2 groups (P < 0.05), but difference was not significant between 2?groups (P > 0.05). At 6?months after operation, the Merled'Aubigne-Postel score of hip function in the trial group was 15.950+/-1.504, showing no significant difference when compared with the control group (15.895+/-1.629) (t= -0.110, P=0.913). The fracture displacement was (0.750+/-1.070) mm in the trial group and was (0.842+/-1.068) mm in the control group, showing no significant difference (t= -0.269, P=0.789). The X-ray films showed that all fractures healed in 2?groups. The healing time was (16.10+/-2.07) weeks in the trial group and was (15.84+/-2.14) weeks in the control group, showing no significant difference (t =0.382, P=0.075). CONCLUSIONS: Reconstruction belt for complicated acetabular fracture by combined anterior and posterior approaches has similar effectiveness to reconstruction plate, but the number of plate shaping, plate shaping time, and perspective times are fewer. PMID- 29786276 TI - [COMPARATIVE STUDY ON FIXATION WITH PERCUTANEOUS CANNULATED SCREWS ASSISTED BY ROBOT NAVIGATION AND CONVENTIONAL SURGERY WITH MANUAL POSITIONING FOR FEMORAL NECK FRACTURES]. AB - OBJECTIVE: To investigate the effectiveness and the advantage of fixation with percutaneous cannulated screws assisted by robot navigation in the treatment of femoral neck fractures by comparing with the conventional surgery. METHODS: Between January 2013 and December 2014, 20 patients with femoral neck fracture were treated by internal fixation with percutaneous cannulated screws assisted by robot navigation (navigation group), another 18 patients undergoing conventional surgery with manual positioning were chosen as the control group. There was no significant difference in gender, age, cause of injury, the injury side, time from injury to operation, and the classification of fractures between 2 groups (P > 0.05). The operation time, X-ray fluoroscopy time, blood loss, frequency of guide pin insertion, and healing time were recorded. At 1 week after operation, the parallel degree of screws was measured on the anteroposterior and lateral X ray films; the Harris score was used to evaluate the hip function. RESULTS: All incisions of 2?groups healed by first intention after operation. There was no significant difference in operation time between 2?groups (t= -1.139, P=0.262). The blood loss, frequency of guide pin insertion, and X-ray fluoroscopy time of navigation group were significantly less than those of control group (P < 0.05). There were 2 screws penetrating into the joint cavity in control group. The patients were followed up 12-24 months with an average of 18 months. The navigation group got significantly better parallel degree of screws than control group on the anteroposterior and lateral X-ray films (t=25.021, P=0.000; t=18.659, P=0.000). Fractures healed in all patients of navigation group (100%), and the healing time was (21.8+/-2.8) weeks; fracture healed in 16 patients of control group (88.9%), and the healing time was (24.0 +/- 3.7) weeks. There was no significant difference in healing rate and healing time between 2 groups (chi2=2.346, P=0.126; t=1.990, P=0.055). The Harris score of navigation group (87.1+/-3.7) was significantly higher than that of control group (79.3+/-4.7) at last follow-up (t= -5.689, P=0.000). CONCLUSIONS: Cannulated screw fixation assisted by robot navigation is a good method to treat femoral neck fractures, which has the advantages of more accurate positioning, better hip function recovery, less surgical trauma, and shorter X-ray exposure time. PMID- 29786277 TI - [EFFECTIVENESS OF ONE-STAGE REPAIR AND RECONSTRUCTION FOR KNEE DISLOCATION WITH MULTIPLE LIGAMENT INJURIES]. AB - OBJECTIVE: To evaluate the surgical procedure and short-term effectiveness of one stage repair and reconstruction of knee dislocation with multiple ligament injuries (KDMLI). METHODS: Between September 2010 and April 2014, 9 cases (9 knees) of KDMLI were treated. There were 7 males and 2 females with an average age of 42 years (range, 27-57 years). Injury was caused by traffic accident in 3 cases, heavy-weight crushing in 3 cases, sports sprain in 2 cases, and falling from height in 1 case. The average time from injury to operation was 11 days (range, 3-19 days). The results of posterior drawer test and Lachman test were positive in all patients. The results of varus stress testing were three-degree positive in 4 cases, and the results of valgus stress testing were three-degree positive in 6 cases. The Lysholm score of knee was 27.2+/-6.3; the International Knee Documentation Committee (IKDC) score was 29.7+/-6.5; and the range of motion (ROM) was (52.6+/-12.8) degrees . All patients suffered from posterior cruciate ligament (PCL) injury and femoral avulsion injury of anterior cruciate ligament (ACL). Combined injuries included medial collateral ligament (MCL) injury in 4 cases (medial meniscus injury in 1 case), lateral collateral ligament (LCL) injury in 2 cases, and MCL and LCL injuries in 2 cases (medial meniscus and lateral meniscus injuries in 1 case). Autologous harmstring tendon was used to reconstruct PCL under arthroscopy combined with limited open in situ suture for repair of femoral avulsion injury of ACL, and repair of MCL, LCL, and other injury in one-stage operation. RESULTS: All incisions healed by first intention. Joint effusion of knee occurred in 1 case and was cured after removal of fluid combined with pressure bandage. All patients were followed up 12-36 months with an average of 22 months. At last follow-up, the result of posterior drawer test was negative in all patients. The results of Lachman test were one-degree positive in 2 cases; the result of varus stress testing was one-degree positive in 1 case; the results of valgus stress testing were one-degree positive in 2?cases; and flexion dysfunction of the knee was observed in 1 case. The Lysholm score of knee was 87.3+/-6.6; the IKDC score was 88.9+/-6.8; and the ROM was (121.7+/-12.3) degrees , all showing significant differences when compared with preoperative ones (t=44.246, P=0.000; t=37.903, P=0.000; t=19.894, P=0.000). CONCLUSIONS: For KDMLI, one-stage repair and reconstruction using autologous harmstring tendon to reconst ruct PCL under arthroscopy combined with limited open in situ suture repair of femoral avulsion injury of ACL, and repair MCL, LCL, and other injury has such advantages as minimal invasiveness, reliable fixation, less complications, and fast recovery, which can significantly improve the stability, ROM, and function of knee and obtain good short-term effectiveness. PMID- 29786278 TI - [BRIDGED DURAL SUSPENSION FOR CRANIOPLASTY BY USING THREE- DIMENSIONAL MOULDING TITANIUM MESH]. AB - OBJECTIVE: To investigate the value of bridged dural suspension for cranioplasty by using three- dimensional moulding titanium mesh. METHODS: A retrospective analysis was made on the clinical data of 156 patients with skull defects, who underwent cranioplasty using three-dimensional moulding titanium mesh between April 2012 and October 2015. Bridged dural suspension was performed in 73 patients (bridging group) and routine cross mesh dural suspension in 83 patients (routine group). There was no significant difference in gender, age, and causes, duration, and area of skull defects between 2 groups (P > 0.05), and they were comparable. The operation time, hospitalization time, and postoperative complication were recorded for analysis. RESULTS: The operation time was (86.7+/ 13.5) minutes in bridging group and was (84.3+/-16.3) minutes in routine group, showing no significant difference (t=1.061, P=0.290); but hospitalization time of bridging group [(16.8+/-2.7) days] was significantly shorter than that of routine group [(18.7+/-5.7) days] (t=-2.661, P=0.009). Postoperative complications occurred in 16 patients of routine group (19.3%), including epidural hydrops in 13 cases, epidural hematoma in 2 cases, and epidural infection in 1 case, while epidural hydrops occurred in 4 cases of bridging group (5.5%). There was significant difference in complication rate between 2 groups (chi2=6.616, P=0.010). All patients were followed up 5-46 months (mean, 25.2 months). The satisfactory cosmetic results of the skull were obtained, and CT images showed good coverage of defect. CONCLUSIONS: Bridged dural suspension for cranioplasty is more simple and effective than routine cross mesh suspension, and it is beneficial to reduction of postoperative complications. PMID- 29786279 TI - [CONDITIONED MEDIUM OF BONE MARROW MESENCHYMAL STEM CELLS ALLEVIATE INHIBITING EFFECT OF DEXAMETHASONE ON OSTEOGENETIC CAPABILITY OF OSTEOBLAST]. AB - OBJECTIVE: To explore the paracrine effect of bone marrow mesenchymal stem cells (BMSCs) on dexamethasone-induced inhibition of osteoblast function in vitro. METHODS: The serum free conditioned medium of mouse BMSCs cultured for 24 hours was prepared for spare use. The 3rd passage of MC3T3-E1 cells were divided into 4 groups: the control group (group A), dexamethasone group (group B), dexamethasone+BMSCs conditioned medium (1:1) group (group C), and BMSCs conditioned medium group (group D). After 24 hours of culture, the alkaline phosphatase (ALP) content was determined; the protein expressions of RUNX2 and Osteocalcin were detected by Western blot; and the gene expressions of collagen type I-alpha 1 (COL1A1), RUNX2, ALP, and Osteocalcin were detected by real-time fluorescence quantitative PCR (RT-qPCR); alizarin red staining was used to observe calcium nodules formation at 21 days. RESULTS: After cultured for 24 hours, ALP content was significantly lower in groups B, C, and D than group A, and in group B than groups C and D (P < 0.05), but no significant difference was found between groups C and D (P > 0.05). The relative protein expression of RUNX2 of group B was significantly lower than that of groups A, C, and D (P < 0.05), but difference was not significant between groups A, C, and D (P > 0.05). The relative protein expression of Osteocalcin was significantly lower in group B than groups A, C, and D, in groups A and C than group D (P < 0.05), but difference had no significance between groups A and C (P > 0.05). The relative gene expressions of RUNX2, Osteocalcin, COL1A1, and ALP of groups B, C, and D were significantly lower than those of group A (P < 0.05); the relative gene expressions of RUNX2, Osteocalcin, and ALP were significantly higher in group D than groups B and C, in group C than group B (P < 0.05). The gene expression of COL1A1 was significantly higher in group D than group B (P < 0.05), but difference was not significant between groups B and C, and between groups C and D (P > 0.05). The cells of group A all died at 6 days after culture; at 21 days, the calcium no dule staining was positive by alizarin red in groups B, C and D, and the degree of the staining gradually increased from groups B to D. CONCLUSIONS: BMSCs conditioned medium can alleviate the inhibitory effect of dexamethasone on osteoblasts function. PMID- 29786280 TI - [ARTHROSCOPIC SINGLE-BUNDLE ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION USING SIX STRAND AUTOGRAFT HAMSTRING TENDON PLUS TightRope SUSPENSION PLATE]. AB - OBJECTIVE: To explore the effectiveness of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction using six-strand autograft hamstring tendon plus TightRope suspension plate. METHODS: Between September 2014 and August 2015, 24 patients with ACL rupture accepted arthroscopic single-bundle ACL reconstruction using six-strand autograft hamstring tendon plus TightRope suspension plate. There were 16 males and 8 females with an age range of 18-54 years (mean, 36.2 years). The disease causes included sport injury in 15 cases, traffic accident injury in 4 cases, and sprain in 5 cases. The mean time from injury to operation was 3.9 months (range, 18 days to 8 months). The results of anterior drawer test, pivot shift test, and Lachman test were positive before operation. The preoperative International Knee Documentation Committee (IKDC) score was 38.69+/-3.85 and Lysholm knee functional score was 36.45+/-7.85. RESULTS: The incisions healed by first intention. No infection, deep vein thrombosis, or vessel and nerve injuries occurred. MRI showed the good tunnel position and ACL morphology. All patients were followed up 6-16?months with an average of 12 months. At last follow-up, Lysholm and IKDC scores were significantly increased to 81.31+/-7.58 and 79.62+/-5.39 respectively (P < 0.05). The results of anterior drawer test were negative in 17 cases and positive degree I in 7 cases; the results of Lachman test were negative in 20 cases and positive degree I in 4?cases; the results of pivot shift test were negative in 21 cases and positive degree I in 3 cases; and all showed significant differences compared with preoperative results (P < 0.05). CONCLUSIONS: Arthroscopic single-bundle reconstrustion using six-strand autograft hamstring tendon plus TightRope suspension plate is a simple technique for ACL reconstruction, which can obtain satisfactory short-term effectiveness. PMID- 29786281 TI - [EXPERIMENTAL STUDY ON RECONSTRUCTION OF PARTIAL DEFECTS OF CERVICAL TRACHEA WITH BACTERIAL CELLULOSE PATCH IN RABBITS]. AB - OBJECTIVE: To investigate the feasibility of bacterial cellulose patch to repair and reconstruct rabbit tracheal defect, so as to lay the foundation for the development of bacterial cellulose artificial trachea. METHODS: Thirty adult rabbits (weighing, 2.5-3.5 kg) were selected to establish full-thickness defect of the cervical trachea (1.0 cm*0.6 cm in size) which involved the anterior and side walls and 2-3 rings. Defect was repaired with sheet bacterial cellulose (1.2?cm in diameter and 6 layers) in experimental group (n=15), and with autologous cervical fascia in control group (n=15). The general condition of the animals was observed after operation; after 4, 8, and 12 weeks, the samples were obtained for measuring the tracheal stenosis degree, counting new microvessels, and observing lumen reconstruction situation by scanning electron microscope. RESULTS: Three rabbits died of infection, tracheal stenosis, or asphyxia caused by airway secretions retention in 2 groups respectively, and the other rabbits survived to the end of experiment. Gross observation showed that reconstruction materials gradually adhered?to?adjacent?tissue and were enwrapped?by connective tissue, small blood vessels like nutrient vessel were seen in 2 groups; no significant difference was found in the tracheal lumen stenosis degree between 2 groups (P > 0.05). Histological observation showed that the continuous growth of mucosal epithelial cells was observed near patch and anastomosis site with time, and cell morphology gradually turned mature in experimental group; while mucosal epithelial cells arranged loosely in control group. At each time point, new capillaries of experimental group were significantly more than those of control group (P < 0.05). Scanning electron microscope observation showed the continuous epithelioid cells were observed at anastomosis site with time, and gradually grew into the middle of the patch in experimental group; while less and discontinuous epithelioid cells were observed in control group. CONCLUSIONS: Bacterial cellulose patch is feasible to reconstruct cervical tracheal defect in rabbits, and the new mucosa is formed early and completely, so it is expected to be used as artificial trachea material. PMID- 29786282 TI - [APOPTOSIS IN HUMAN OSTEOSARCOMA CELL LINE MG63 INDUCED BY PYROPHEOPHORBIDE-a METHYL ESTER-MEDIATED PHOTODYNAMIC THERAPY]. AB - OBJECTIVE: To explore the effect of pyropheophorbide-a methyl ester-mediated photodynamic therapy (MPPa-PDT) on the apoptosis in human osteosarcoma cell line MG63 and the underlying mechanism. METHODS: Human osteosarcoma MG63 cells in logarithmic growth phase were divided into 4 groups: blank control group (control group), the MPPa treatment group (MPPa group), the light irradiation group (LED group), and MPPa-PDT treatment group (MPPa-PDT group). MPPa-PDT group and MPPa group were incubated with MPPa (0.75?MUmol/ L) for 20 hours in dark condition; control group and LED group were incubated with equal volume of fresh medium for 20 hours in the same condition. After washing with PBS and replacement with fresh culture medium, LED group and MPPa-PDT group cells were exposed to light (4.8 J/cm2) for 120 seconds. After light exposure, all groups were cultured in dark condition again. Then cellular morphology changes were observed by an inverted phase contrast microscopy, endoplasmic reticulum morphology changes were observed by transmission electron microscopy, cellular apoptosis was detected by Hoechst33258 nuclear staining, cell apoptotic rate and the levels of Ca in cells were analyzed by flow cytometry, the expression of p-PERK, C/EBP homologous protein (CHOP), cleaved-Caspase-12 were assayed by Western blot. RESULTS: In MPPa PDT group, the retracted and round cells were observed; Hoechst33258 nuclear staining showed nuclear condensation, fragmentation, and other typical apoptotic morphological changes; the cell apoptotic rate (48.76%+/-3.54%) was significantly higher than that of control group (5.04%+/-0.41%), MPPa group (5.33%+/-0.38%), and LED group (6.48%+/-0.46%) (P < 0.05); the levels of Ca2+ in cells (485.29+/ 58.77) was also significantly higher than that of control group (97.24+/-4.77), MPPa group (97.95+/-6.30), and LED group (101.17+/-5.26) (P < 0.05); swelling endoplasmic reticulum was observed under transmission electron microscope; the expressions of p-PERK, CHOP, and cleaved-Caspase-12 gradually increased at 1, 3, and 6 hours after treatment respectively, which were significantly higher than those of the other groups (P < 0.05). There was no typical apoptotic morphological changes and endoplasmic reticulum morphological changes in control group, MPPa group, and LED group, and there was no significant difference in the above indexes among 3 groups (P > 0.05). CONCLUSIONS: MPPa-PDT can significantly induce apoptosis in MG63 cells. The endoplasmic reticulum stress pathway is involved in the MPPa-PDT induced apoptosis. PMID- 29786283 TI - [EFFECT OF Wnt/beta-catenin SIGNAL PATHWAY ON APOPTOSIS IN STEROID-INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN RATS]. AB - OBJECTIVE: To investigate the effect of Wnt/beta-catenin signal pathway on the apoptosis in steroid-induced avascular necrosis of femoral head (SANFH) in rats. METHODS: Seventy-two male Sprague Dawley rats (weighing, 200-230 g) were randomly divided into the control group (group A, n=24), the model group (group B, n=24), and the intervening group (group C, n=24). The rats in groups B and C were injected with lipopolysaccharide and methylprednisolone (MPS) to establish the SANFH model. The rats in group C were injected intramuscularly with human recombinant secreted frizzled related protein 1 (SFRP1) [1 MUg/(kg.d)] at the first time of MPS administration for 30 days. The rats in group A received saline injection at the same injection time of group B. The general condition of rats in groups B and C was observed during modeling and after modeling. At 2, 4, and 8 weeks after last injection of MPS, 8?rats were sacrificed to harvest the femoral head. Histological staining was performed to evaluate osteonecrosis. Apoptosis was detected via TUNEL staining. The expressions of Wnt/beta-cate nin pathway signaling molecules (activated beta-catenin and c-Myc) were detected by immunohistochemistry and Western blot. RESULTS: Six rats were added in groups B and C because of 6 deaths. The other rats survived to the end of experiment. Normal bone structure was observed in group A; osteonecrosis of bone structure disturbance and disruption of the trabecula were found with time in groups B and C. Group C had the highest empty lacuna rate and apoptosis rate, followed by groups B and A, showing significant difference between groups (P < 0.05). The expression levels of activated beta-catenin and c-Myc were significantly lower in group C than groups A and B (P < 0.05), and in group B than group A (P < 0.05). CONCLUSIONS: Wnt/beta-catenin signal pathway is involved in the pathogenesis in early SANFH model and its?possible mechanism?is to affect the cell cycle and cell apoptosis by the regulation of c-Myc expression. PMID- 29786284 TI - [CLASSIFICATION AND SURGICAL TREATMENT OF MUCOUS CYSTS OF DISTAL INTERPHALANGEAL JOINT]. AB - OBJECTIVE: To investigate the self-made classification criterion for mucous cysts of distal interphalangeal joint and the effectiveness of the surgical treatment. METHODS: Between July 2008 and August 2015, 33 patients with mucous cysts of distal interphalangeal joint were treated, and the clinical data were retrospectively analyzed. Among 33 cases, 15 were male and 18 were female, aged from 45 to 74 years (mean, 58 years). The disease duration ranged from 3 weeks to 1 year (mean, 5 months). The cyst located at thumb in 18 cases, index finger in 4 cases, middle finger in 6 cases, ring finger in 4 cases, and little finger in 1 case. According to location, mucous cysts were typed: proximity to one side of the finger extensor tendon and deviation from the midline of the finger named lateral type (22 cases); and at both sides of the finger extensor tendon named intermediate type (11 cases). The bilateral digital dorsal incision was made in the intermediate type patients, and the reverse L-shaped incision was made in the lateral type patients, then the degenerative tissue was resected, the osteophyte was removed, and the capsule was repaired; finally, mucous cysts were resected. RESULTS: All the patients were followed up 4 months to 2 years (mean, 14.5 months). The incision healed by first intention without infection after operation. Clinical symptoms obtained improvement and no recurrence was observed in 29 patients except 4 patients who died of other diseases during follow-up. CONCLUSIONS: A surgical treatment for mucous cysts of distal interphalangeal joint is feasible according to the self-made classification criterion and it has the advantage of simple operation and definite effectiveness. PMID- 29786286 TI - [TOE FIBULAR-DORSAL ARTERY FLAP ANASTOMOSED TO DORSAL DIGITAL ARTERY IN REPAIRING DORSAL SOFT TISSUE DEFECT OF FINGERS]. AB - OBJECTIVE: To discuss the effectiveness of free toe fibular-dorsal artery flap anastomosed to dorsal digital artery in repairing dorsal soft tissue defect of fingers. METHODS: Between May 2010 and September 2015, 28 patients with dorsal soft tissue defect of fingers were treated, including 17 males and 11 females with an average age of 23.8 years (range, 15-55 years). The reasons of injuries were machine twist (15 cases), heavy pound (4 cases), the sharp cut (5 cases), and hot crush (4 cases). The time from injury to admission was 30 minutes to 12 hours (mean, 1.5 hours). The involved fingers included thumb (3 cases), index finger (8 cases), middle finger (6 cases), ring finger (6 cases), and little finger (5 cases). The area of soft?tissue?defects ranged from 2.0 cm*1.5 cm to 3.5 cm*2.5 cm, and the area of free toe fibular-dorsal artery flap ranged from 2.8 cm*1.7 cm to 3.8 cm*2.8 cm. The blood supply of the flaps were reconstructed by anastomosing the toe fibular-dorsal artery, vein, and nerve to the dorsal digital artery, vein, and nerve, respectively. The donor site was repaired by free skin graft. RESULTS: The operation time was 1.5-5.5 hours (mean, 2.5 hours); the blood loss during operation was 10-50 mL (mean, 30 mL). Vessel?crisis?occurred?in?1 case, and the flap survived after symptomatic treatment. The other flaps survived and the wounds healed with stage I; the skin grafts at donor site survived and the incisions healed with stage I. Twenty-eight cases were followed up 6-24 months (mean, 8 months). The appearance of flaps was good, and two-point discrimination was 3.5-12.0 mm (mean, 5.3 mm) at 6 months after operation. The fingers function of grab and pinch recovered. According to the standard functional evaluation issued by Hand Surgery Association of Chinese Medical Association, the results were excellent in 20 cases and good in 8 cases, with an excellent and good rate of 100% at 6 months after operation. The donor sites of toe were smooth and had no depression. The patients had normal gait. CONCLUSIONS: Free toe fibular-dorsal artery flap anastomosed to dorsal digital artery in repairing dorsal soft tissue defect of fingers can obtain satisfactory effectiveness in appearance and function of fingers, and has the advantages of modified repair and less injury at donor site. PMID- 29786285 TI - [RESEARCH PROGRESS OF FENESTRATED PEDICLE SCREW]. AB - OBJECTIVE: To review the research background, biomechanical characteristics, and clinical application of fenestrated pedicle screw (FPS). METHODS: The recent literature about the study and application of FPS was reviewed, analyzed, and summarized. RESULTS: Compared with the technique of conventional pedicle screw augmentation, FPS can be augmented with polymethyl methacrylate (PMMA) through inner central pore and side holes. Hence, the augmentation process of FPS is more convenient during operation. The biomechanics of PMMA augmented FPS is strong enough for instrumentation in osteoporotic vertebra body and the way of FPS PMMA augmentation can reduce the risk of PMMA leakage. CONCLUSIONS: FPS is an innovation in the technology of spinal instrumentation, which is expected to improve the clinical outcome of PMMA augmented pedicle screw in osteoporotic vertebra body fixation. PMID- 29786287 TI - [PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL CHARACTERISTICS OF POROUS TANTALUM AND ITS APPLICATION PROGRESS IN SPINAL SURGERY]. AB - OBJECTIVE: To summarize the physicochemical properties, manufacturing technique, and biological characteristics of porous tantalum and its application progress and related problems in spinal surgery. METHODS: The domestic and foreign related literature about porous tantalum was summarized and analyzed. RESULTS: Porous tantalum is characterized by high porosity, high coefficient of friction, low elastic modulus, good biocompatibility, and superior osseointegration capability. Its manufacture methods include chemical vapor deposition and infiltration technique, foam impregnation and powder metallurgy technique, and heat treatment method. Good clinical efficacy has achieved in the application of porous tantalum interbody fusion Cage in cervical and lumbar fusion surgery, but there is controversy in spinal fusion rate, especially in cervical fusion rate. Surface modification can increase the osseointegration capability of porous tantalum and intervertebral bony fusion. CONCLUSIONS: Good clinical efficacy has achieved in the application of porous tantalum interbody fusion Cage in lumbar fusion surgery, while there is a dispute in cervical fusion surgery. In order to further observation, studies with more patients and longer follow-up would be needed. PMID- 29786288 TI - [SURGICAL TREATMENT OF Seymour FRACTURES IN CHILDREN AND ADOLESCENTS]. AB - OBJECTIVE: To discuss the treatment method and effectiveness of Seymour fracture in children and adolescents. METHODS: Between January 2013 and November 2015, 26 children and adolescents with Seymour fractures were treated. There were 18 males and 8 females, aged from 1 year and 1 month to 17 years (median, 8.2 years). The injury causes included crush in 14 cases, bruise in 10 cases, and puncture in 2 cases. The thumb was involved in 2 cases, index finger in 1 case, middle finger in 12 cases, ring finger in 6 cases, and little finger in 5 cases. The time from injury to operation was 1-15 hours (mean, 3.2 hours). The patients underwent debridement, nail removal, nail matrix repair, closed reduction and osteosynthesis with Kirschner wires, and splinting in emergency. Kirschner wires and splints were removed at 4 weeks after surgery, and functional exercises were done. RESULTS: All wounds healed by first intention without infection. The follow up duration was 2-24 months (mean, 12.3 months). The fracture healing was obtained at 1-2 months (mean, 1.4 months) on X-ray film, and no complications of nonunion, malunion, re-displacement, premature epiphyseal closure, or no growth of the nails occurred. Nail deformity developed in 1 case and no re-operation was given. At last follow-up, 1 patient had 10 degrees extension limitation of the distal interphalangeal joint, but the flexion was normal. The motion range of distal interphalangeal joint was 0-75 degrees , showing no significant difference when compared with that of contralateral side (0-78 degrees ). CONCLUSIONS: The effectiveness for treating Seymour fracture is satisfactory by debridement, nail removal, nail matrix repair, closed reduction and osteosynthesis with Kirschner wires, and splinting in emergency. PMID- 29786290 TI - [AN ANTERIOR NEUROVASCULAR INTERVAL APPROACH FOR FIXATION OF ULNA CORONOID PROCESS FRACTURE]. AB - OBJECTIVE: To investigate the advantages and effectiveness of anterior neurovascular interval approach for fixation of ulna coronoid process fracture. METHODS: Between February 2011 and April 2015, 8 patients with ulna coronoid process fracture were treated with open reduction and internal fixation by anterior neurovascular interval approach. There were 5 males and 3 females, aged from 14 to 62 years (mean, 34 years). Fractures were caused by falling in 5 cases, traffic accident in 2 cases, and crashing in 1 case. The time between injury and operation was 1-6 days (mean, 3.5 days). According to Adams classification, there were 4 cases of type II, 1 case of type III, 2 cases of type IV, and 1 case of type V. In 1 patient with joint instability, lateral collateral ligament repair was given through another incision after fixation of coroniod fracture and the hinged external fixator, and plast splin was used to fix in the other patients; function exercise was done after removal of external fixtion. RESULTS: All incisions healed by first intention, and no complications of neurovascular injury and deep infection occurred. All patients were followed up 6-48 months (mean, 22 months). The healing time of fracture was 8-15 weeks (mean, 12.6 weeks). Mild myositis ossificans occurred in 1 case. The flexionextension arc of the elbow was (125.00+/-7.07) degrees and the forearm rotation was (135.00+/-7.07) degrees , showing no significant difference when compared with those of normal side[(126.88+/-7.53) degrees and (139.38+/-8.21) degrees ] (t=0.469, P=0.654; t=2.198, P=0.054). According to Morrey's scale, the results were excellent in 6 cases, good in 2 cases; the excellent and good rate was 100%. CONCLUSIONS: Anterior neurovascular interval approach for reduction and internal fixation of ulna coroniod fractures has the advantages of simple operation, less trauma, and larger operative field. It can be used alone or combined with other surgical approaches. PMID- 29786289 TI - [EFFECTIVENESS COMPARISON OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION BETWEEN BY AUTOLOGOUS AND ALLOGENEIC TENDON GRAFTS COMBINED WITH HOOK PLATE FIXATION FOR TREATING ACROMIOCLAVICULAR JOINT DISLOCATION]. AB - OBJECTIVE: To compare the effectiveness of coracoclavicular ligament reconstruction between by using autologous plantaris tendon graft combined with hook plate fixation and allogeneic tendon graft combined with hook plate fixation for treating acromiocavicular joint dislocation. METHODS: Thirty-three patients with acromioclavicular joint dislocation who accorded with the inclusion criteria between January 2013 and June 2014 were assigned into 2 groups. The patients were treated with autologous plantaris tendon graft combined with hook plate fixation in group A (n=17), and with allogeneic tendon graft combined with hook plate fixation in group B (n=16). Thirteen-one patients was followed up more than 12 months (15 in group A and 16 in group B). There was no significant difference in gender, age, cause of injury, sides, time between injury and surgery, and type of dislocation (P>0.05). The assessments included operation time, hospitalization time, hospitalization expenses, shoulder range of motion, gap of acromioclavicular, Constant-Murley scores, and visual analogue scale (VAS) for pain. RESULTS: The operation time of group A was significantly longer than that of group B, and the hospitalization expense was significantly lower than that of group B (P<0.05). There was no significant difference in hospitalization time (t=1.046, P=0.316). The incisions healed by first intention, and hook plate was removed after 3 months. The mean follow-up time was 21.3 months (range, 19-34 months) in group A and was 23.7 months (range, 18-37 months) in group B. X-ray examination showed no osteolysis. There was no significant difference in gap of acromiocavicular between 2 groups at preoperation, 1 week after operation, and last follow-up (P>0.05). No redislocation of acromioclavicular joint and rejection reaction occurred during follow-up. At last follow-up, there was no significant difference in shoulder range of motion, Constant-Murley score, and VAS score between 2 groups (P>0.05). CONCLUSIONS: Coracoclavicular ligament reconstruction by autologous plantaris tendon or allogeneic tendon graft combined with hook plate fixation for the treatment of acromioclavicular joint dislocation can achieve good effectiveness. The appropriate treatment should be chosen according to the patient's economic situation. PMID- 29786291 TI - [CLINICAL OBSERVATION OF ROTATING-PLATFORM PROSTHESIS FOR VALGUS KNEE DEFORMITY]. AB - OBJECTIVE: To investigate the effectiveness of rotating-platform prosthesis for valgus knee deformity in total knee arthroplasty (TKA). METHODS: A retrospective analysis was made on the clinical date of 25 cases (28 knees) of valgus deformity undergoing primary TKA by using Gemini MK II rotating-platform prosthesis. There were 6 males (7 knees) and 19 females (21 knees), aged from 47 to 82 years, with an average age of 64.8 years. The unilateral knee was involved in 22 cases and the bilateral knees in 3 cases. The causes included osteoarthritis in 20 cases (22 knees), rheumatoid arthritis in 4 cases (5 knees), and traumatic arthritis in 1 case (1 knee). The disease duration was 2-22 years (mean, 10.4 years). The main clinical symptoms were arthralgia combined with limited movement. According to the Keblish grade, there were 13 knees of mild deformity, 11 knees of moderate deformity, and 4 knees of severe deformity. RESULTS: All incisions healed by first intension. No complications of infection, cutaneous necrosis, deep venous thrombosis, and pulmonary embolism occurred. The postoperative follow-up duration was 12-60 months (mean, 25.4 months). Medial instability and palsies of nervus peroneus communis occurred in 1 and 2 cases respectively, and all were cured after symptomatic treatment. No patellar and polysthylene insert dislocation, prosthetic loosening or infection was observed. The Hospital for Special Surgery (HSS) score, femoral tibial angle, maximun flexion and extension angles, knee range of motion, and patellar score were significantly improved at last follow-up when compared with preoperative ones (P<0.01). CONCLUSIONS: The rotating-platform prosthesis for valgus deformity can obtain satisfactory effectiveness, but it requires precise soft tissue balancing technology, and the long-term effectiveness remains further observation. PMID- 29786292 TI - [CLINICAL OBSERVATION OF IMPROVING AXIAL OFFSET BY USING Ilizarov BONE TRANSPORT TECHNOLOGY]. AB - OBJECTIVE: To explore the effectiveness of Ilizarov technique in improving bone transport axial offset. METHODS: Between January 2010 and December 2014, 14 patients with tibial fracture were treated by using Ilizarov technique. Of 14 cases, 11 were male and 3 were female, aged 18-70 years (mean, 38.8 years); there were 10 cases of infective bone defect and 4 cases of non-infective bone defect. According to Paley typing, 7 cases were rated as type B1(bone defect without shortening) and 7 cases as type B3(bone defect with shortening). The injury to operation time was 1 to 72 months (mean, 11.9 months). Ilizarov fixation was used for type architecture and adjusting fixed bone removal of half the distance between the needle and the ring, changing the auadrilateral edges, adjusting the convolution relationship between the bone removal section and bone segment involution, and adjusting the two force lines of bone segment involution end so as to make the limb lines of force satisfactory. RESULTS: The patients were followed up 9-31 months (mean, 19.1 months). Four cases achieved natural bone healing at last follow-up, bone healing was obtained in 10 cases after bone graft. At 1 week after operation, X-ray films showed angulation in the coronal plane in 10 cases (3-12 degrees , 4.9 degrees on average) and in the sagittal plane in 9 cases (2-12 degrees , 3.8 degrees on average); axial offset was observed in 6 cases (43%), which was corrected in 5 cases except 1 case. At last followup, angulation in the coronal plane was observed in 5 cases (2-4 degrees , 2.6 degrees on average), angulation in the sagittal plane in 6 cases (2-6 degrees , 4.1 degrees on average), and axial offset in 1 case (7%), which were significantly improved when compared with ones at 1 week. According to Paley evaluation criteria, the osseous results were excellent in 12 cases and good in 2 cases; the functional results were excellent in 12 cases and good in 2 cases at last follow-up. CONCLUSIONS: Axial offset in the Ilizarov bone transport relatively common. By adjusting fixed bone removal of half the distance between the needle and the ring, the axial offset can be improved. PMID- 29786293 TI - [CLASSIFICATION OF ADULT CUBOID FRACTURE AND EFFECTIVENESS ANALYSIS]. AB - OBJECTIVE: To study the classification criteria of adult cuboid fracture and its guidance feasibility and effect of treatment. METHODS: A retrospective analysis was made on the clinical data of 415 adult patients (416 feet) with cuboid fractures who had complete CT data treated between May 2009 and April 2014. There were 337 males and 78 females, aged 19 to 64 years (mean, 38.8 years). The left foot, right foot, and bilateral feet were involved in 220 cases, 194 cases, and 1 case respectively. The causes of injury were sprain in 106 cases, traffic accident in 65 cases, falling from height in 129 cases, and heavy crushing in 115 cases. The interval of injury and hospitalization was 2 hours to 3 days (mean, 8.5 hours). Based on CT findings, the classification criteria of cuboid fracture was proposed and methods of treatment was statistically analyzed. The external fixation surgery was performed in patients of type I (285 feet), type IIa (18 feet), and type III (5 feet); open reduction and internal fixation were performed in patients of type IIb (41 feet) and type III (67 feet), and bone grafting was used to repair defects in 58 feet (type III). RESULTS: All patients were followed up 1 year to 5 years and 11 months (mean, 2 years and 3 months). Primary healing of incision was obtained. In patients with type I fracture, fracture healed in 165 feet at 4-6 weeks (mean, 5.5 weeks), fracture did not heal in the other 120 feet; the American Orthopaedic Foot and Ankle Society (AOFAS) score was 95 100(mean, 96.7) at last follow-up. In patients with type II fracture, fracture healed in all feet at 6-8 weeks (mean, 6.5 weeks); the AOFAS score was 92 100(mean, 95.5) at last follow-up. In patients with type III fracture, malunion was observed at 6-8 weeks in 5 feet undergoing external fixation, and in 9 feet undergoing open reduction and internal fixation with foot lateral column shortening, forefoot abduction deformity, osteoarthritis, lateral foot pain; fracture healed at 8-12 weeks in 58 feet undergoing open reduction and internal fixation, without osteoarthritis, cuboid bone shortening, and pain at cuboid bone; and AOFAS score was 75-97(mean,93.5) at last follow-up. CONCLUSIONS: The classification criteria of cuboid fracture proposed based on CT examination is feasible and has guiding significance to the choice of treatment method. PMID- 29786294 TI - [CLINICAL EXPERIENCE OF RETROGRADE REPLANTATION FOR AMPUTATED TOE]. AB - OBJECTIVE: To summarize the clinical experience of the retrograde replantation for amputated toe. METHODS: Between January 2010 and August 2015, 11 cases of amputated toes (15 toes) were treated by the retrograde replantation. All patients were male, with a mean age of 31 years (range, 18-45 years). The causes included cutting injury in 6 cases (9 toes) and crush injury in 5 cases (6 toes). One case had amputated great toe and distal segment of the second toe combined with the third toe nail bed contusion; 1 case had amputated proximal great toe and middle segment of the second and third toes; 1 case had amputated proximal segment of great toe and middle segment of the second toe; 7 cases had amputated distal segment of the great toe; and 1 case had amputated middle segment of the fifth toe. The time from injury to hospital was 1-3 hours (mean, 2 hours). RESULTS: Thirteen toes survived completely after operation. Toe necrosis occurred in 1 toe; partial dorsal skins necrosis and nail bed necrosis occurred in 1 toe, and was cure after repaired with dorsalis pedis island flap. The rate of success for replantation of amputated toes was 93.33% (14/15). X-ray examination showed fracture healing of all survival toes at 8-12 weeks after operation (mean, 10 weeks); internal fixation was removed. Eleven cases were followed up 3-12 months (mean, 7.5 months). The survival toes had good appearance and toenail. The two point discrimination was 9-12 mm (mean, 10 mm) at last follow-up. The patients could walk and run normally. CONCLUSIONS: It is an ideal surgical method to use retrograde replantation to treat amputated toe, with the advantages of simple operation and high survival rate. PMID- 29786295 TI - [DIAGNOSTIC SIGNIFICANCE OF MEDIAL MENISCUS INJURY IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION FAILURE]. AB - OBJECTIVE: To explore the relationship between anterior cruciate ligament (ACL) reconstruction failure and medial meniscus injury and decide whether medial meniscus injury could be the judgment index for ACL reconstruction failure without trauma history. METHODS: Between March 2011 and December 2015, 117 patients underwent ACL reconstruction, and the clinical data were analyzed retrospectively. All patients had no trauma history after ACL resconstruction. MRI examination showed medial meniscus injury in 56 cases (observation group) and no medial meniscus injury in 61 cases (control group). There was no significant difference in gender, age, side, reconstructive surgery, and follow-up time between 2 groups (P>0.05). The KT-2000 arthrometer was used to measure the difference value of tibial anterior displacement between two knees in 30 degrees knee flexion. Then wether the ACL reconsruction failure was judged according to the evaluation criteria proposed by Rijke et al. RESULTS: In observation group, the difference value of tibial anterior displacement was <3 mm in 7 patients, 3-5 mm in 11 patients, and >5 mm in 38 patients. In control group, the difference value of tibial anterior displacement was <3 mm in 31 patients, 3-5 mm in 18 patients, and >5 mm in 12 patients. The ACL reconstruction failure rate of observation group (67.9%) was significantly higher than that of control group (19.7%) (chi2=27.700, P=0.000). CONCLUSIONS: After ACL reconstruction, medial meniscus injury occurs under no trauma history circumstances, indicating ACL reconstruction failure. PMID- 29786296 TI - [PROTECTIVE EFFECT OF GLUCOSAMINE-HYDROCHLORIDE ON CARTILAGE IN BLOOD-INDUCED JOINT DAMAGE IN VIVO]. AB - OBJECTIVE: To discuss the effect of glucosamine-hydrochloride (Glu/Ch) in protecting and repairing the cartilage in blood-induced joint damage (BJD) in vivo. METHODS: Thirty-two adult New Zealand rabbits were randomly divided into 4 groups (n=8):high-dose Glu/Ch treated group (group A), low-dose Glu/Ch treated group (group B), positive control group (group C), and negative control group (group D). A joint bleeding model was established by blood injection into articular cavity in groups A, B, and C. Glu/Ch was given by gavage in groups A (250 mg/kg) and B (21.5 mg/kg) once a day for 8 weeks, and the same dosage of saline was given in groups C and D. The serum cartilage oligomeric matrix protein (COMP), serum chondroitin sulfate 846(CS846), and urinary C-terminal telopepide of type II collagen (CTX-II) were measured at 3 days, 7 days, 2 weeks, and 8 weeks after modeling. The expressions of cytokines such as interleukin 1beta (IL 1beta) and tumor necrosis factor alpha (TNF-alpha) in synovial fluid were analyzed by ELISA at 8 weeks after modeling. The expression of matrix metalloproteinase 13(MMP-13) was detected by immunohistochemistry. Alcian blue staining and Safranin-O staining were performed to calculate the percentage of the positive staining areas. The proteoglycan content was detected by semi quantitative analysis in the articular cartilage. RESULTS: The COMP concentration was significantly higher in groups A, B, and C than group D, and in groups B and C than group A at 3 days after modeling (P<0.05); no significant difference was found among groups A, B, and D at 7 days (P>0.05), and it was significantly lower in groups A, B, and D than group C (P<0.05); there was no significant difference among 4 groups after 2 and 8 weeks (P>0.05). Difference in CS846 concentration had no significance among 4 groups at each time point (P>0.05). The CTX-II concentration of groups A, B, and C was significantly higher than that of group D at each time point (P<0.05); it was significantly lower in group A than groups B and C at 7 days, 2 weeks, and 8 weeks (P<0.05). The TNF-alpha concentration of groups A and B was significantly higher than group D, and was significantly lower than group C at 8 weeks (P<0.05), but no significant difference was observed between groups A and B (P>0.05). The IL-1beta concentration was significantly higher in group C than the other groups (P<0.05), and in group B than groups A and D (P<0.05), but there was no significant difference between groups A and D (P>0.05). The MMP-13 expression was significantly higher in group C than groups A, B, and D (P<0.05), in groups A and B than group D (P<0.05). A significant decrease in the area stained with Alcian blue and Safranin-O was observed in group C. There were significant differences in the percentage of the positive stained areas of Alcian blue and Safranin-O among 4 groups (P<0.05). The relative quantities of proteoglycan from small to large in order was groups C, B, A, and D, respectively, showing significant differences (P<0.05). CONCLUSIONS: The metabolism disorder of cartilage matrix and synovium inflammatory reaction can be observed in rat joint bleeding model. Glu/Ch has certain protective effect on the cartilage after BJD by down-regulating IL-1beta, TNF-alpha, and MMP-13, as well as increasing proteoglycan content in the cartilage. PMID- 29786297 TI - [EFFECTIVENESS EVALUATION OF PERCUTANEOUS MONOAXIAL SCREW COMBINED WITH INJURED VERTEBRAE POLYAXIAL PEDICAL SCREW FIXATION FOR TREATMENT OF THORACOLUMBAR FRACTURES]. AB - OBJECTIVE: To explore the effectiveness percutaneous monoaxial screw combined with polyaxial pedical screw for treating thoracolumbar fracture by comparing with simple polyaxial pedicle screw fixation. METHODS: Between January 2012 and June 2014, 56 cases of thoracolumbar fractures were treated by percutaneous pedicle screw fixation, the clinical data were retrospectively analyzed. Of 56 cases, 30 were treated with percutaneous monoaxial screw combined with percutaneous polyaxial pedical screw fixation (group A), 26 patients with only percutaneous polyaxial pedicle screw fixation (group B). There was no significant difference in gender, age, body mass index, injury causes, time from injury to admission, involved segments, fracture type, and preoperative American Spinal Injury Association (ASIA) stage, visual analogue scale (VAS), the anterior height of the injured vertebrae, Cobb angle, and sagittal index between 2 groups (P>0.05). The operation time, intraoperative blood loss, and complications were recorded and compared between the 2 groups. The VAS score was used to evaluate the improvement of the pain. The sagittal kyphosis Cobb angle, the anterior height of the injured vertebrae, sagittal index, and the average correction (difference between 3 days after oeration and preoperation) and loss degrees (difference between last follow-up and 3 days after operation) were measured on the X-ray films at preoperation, 3 days after operation, and last follow-up. RESULTS: Incision healing at stage I was obtained, no related complications occurred. The operation time and intraoperative blood loss showed no significant difference between 2 groups (P>0.05). The patients were followed up 20-42 months (mean, 32 months) in group A and 21-44 months (mean, 30 months) in group B. VAS score of group A was significantly lower than that of group B at 3 days after operation (t=-2.277, P=0.027), but no significant difference was found at last follow-up (t=-0.289, P=0.774). X-ray examination showed good position of internal fixation, with no broken nails or exit of nail. There were significant differences in the anterior height of the injured vertebrae, Cobb angle, and sagittal index between at preoperation and at 3 days and last follow-up, and between at 3 days and last follow-up in 2 groups (P<0.05). The anterior height of the injured vertebrae, Cobb angle, and sagittal index of group A were significantly better than those of group B at 3 days and last follow-up (P<0.05), and correction degree were significantly higher than those of group B (P<0.05), but loss degree was not significant between 2 groups (P>0.05). CONCLUSIONS: Percutaneous monoaxial screw combined with polyaxial pedicle screw fixation is better than simply polyaxial pedicle screw in effects of treating thoracolumbar fracture under the premise of strictly holding indications. PMID- 29786298 TI - [PEDICLE SUBTRACTION OSTEOTOMY ASSISTED WITH ANTERIOR COLUMN RECONSTRUCTION FOR TREATMENT OF CHRONIC OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURE]. AB - OBJECTIVE: To evaluate the effectiveness of pedicle subtraction osteotomy (PSO) assisted with anterior column reconstruction in the treatment of chronic osteoporotic vertebral compression fracture (OVCF). METHODS: Between January 2008 and October 2014, 11 cases of chronic OVCF were treated. There were 2 males and 9 females, aged 65-76 years (mean, 72.3 years). The vertebral compression fracture segment involved T11 in 2 cases, T12 in 2 cases, L1 in 4 cases, L2 in 2 cases, and L3 in 1 case. At preoperation, the Oswestry disability index (ODI) score was 31.1+/-10.2; kyphosis Cobb angle of fractured vertebrae was (36.5+/-10.2) degrees on the lateral X-ray films of the spine; and distance between C7 plumb vertical line (C7 PL) and sagittal vertical axis (SVA) of the S1 superior border was (5.2+/-2.5) cm. Six cases had spinal cord injury (SCI), including 4 cases of Frankel grade C and 2 cases of grade D. At last follow-up, ODI score, kyphosis Cobb angle of fractured vertebrae, and distance between C7 PL and SVA were recorded and compared with preoperative values. Postoperative Frankle scores were recorded in SCI cases. X-ray film and CT scan were taken to evaluate bone fusion at 12 months after operation. RESULTS: The operation was completed successfully without serious complications. Nerve root radiation symptoms occurred in 2 cases undergoing lumbar PSO, which was relieved after conservative treatment. Cerebrospinal fluid leakage occurred in 1 case and was cured after 2 weeks. All cases were followed up 12-24 months (mean, 15.6 months). No internal fixation failure or pseudarthrosis was found postoperatively.Screw loosening was found in 1 case (2 screws of the upper level) and titanium Cage cutting vertebral body was found in 1 case. Bone fusion was obtained in all cases at 12 months after operation. At last follow-up, ODI score was significantly improved to 13.7+/ 5.7(t=4.417, P=0.018), kyphosis Cobb angle of fractured vertebrae to (7.0+/-15.2) degrees (t=5.113, P=0.009), and the distance between C7 PL and SVA to (2.8+/ 2.2) cm (t=3.285, P=0.032). In 6 SCI cases, Frankle grade was recovered to E (1 case), to D (1 case), and no improvement (2 cases) from C, and to E from D (2 cases). CONCLUSIONS: PSO assisted anterior column reconstruction was an effective method in treatment of chronic OVCF. PMID- 29786299 TI - [BIOMECHANICAL STUDY ON ADJACENT UPPER AND LOWER AND UNILATERAL FRACTURED VERTEBRAL PEDICLE SCREW FIXATION IN TREATMENT OF THORACOLUMBAR FRACTURE]. AB - OBJECTIVE: To investigate the stability of unilateral fractured vertebral pedicle screw fixation in the treatment of thoracolumbar fracture. METHODS: Eighteen fresh calf thoracolumbar spine specimens (T11-L3) were obtained to establish the L1 burst fracture models with Panjabi's high speed trauma apparatus, and were divided into 3 groups:pedicle fixation for adjacent upper and lower vertebrae of fractured vertebra (4 pedicle screws in group A), combined with pedicle screw fixation for unilateral fractured vertebrae (5 pedicle screws in group B), and three-level 6 pedicle fixation (group C). Under normal, fractured, and reconstructed conditions, the range of motion (ROM) of adjacent upper and lower vertebrae of fractured vertebra were measured in flexion, extension, bilateral bending, and axial rotation. Axial stiffness under flexion-compression was measured on the MTS-858 testing system. RESULTS: There was no significant difference in ROM and axial stiffness under normal and fractured conditions in all directions among groups (P<0.05), indicating load balance in the groups. ROM of groups B and C were significantly less than that of group A under reconstructed condition in all directions (P<0.05), but no significant difference was found between group B and group C (P>0.05). Biomechanical test showed that group B was significantly higher than group A in the axial stiffness value (P<0.05), but difference was not significant between group B and group C (P>0.05). CONCLUSIONS: Transpedicular fixation of fractured vertebrae can enhance the stability of the spine. Both unilateral and bilateral fractured vertebral pedicle screw fixations have the same stability. PMID- 29786300 TI - [ANTERIOR APPROACH DEBRIDEMENT AND BONE GRAFTING WITH SELF-LOCKED TITANIUM PLATE INTERNAL FIXATION FOR TREATING LUMBOSACRAL TUBERCULOSIS]. AB - OBJECTIVE: To explore the effectiveness of stage I anterior approach debridement and autologous iliac crest graft with single self-locked titanium plate internal fixation for the treatment of lumbosacral tuberculosis. METHODS: Seven cases of lumbosacral tuberculosis were treated by stage I anterior approach debridement, autologous iliac crest graft, and single self-locked titanium plate internal fixation between February 2010 and October 2014. There were 5 males and 2 females, aged 18-65 years (mean, 41.6 years). The disease duration was 5-21 months (mean, 8 months). The patients had signs and symptoms of pain in lumbosacral region, radiating pain in unilateral lower limb or bilateral lower limbs, decreased muscular strength and disorders of superficial sensation. According to Frankel classification for spinal injury, 1 case was rated as grade C, 3 cases as grade D, and 3 cases as grade E. Preoperative imaging examination suggested L5, S1 lesions in line with the manifestations of tuberculosis; the lumbosacral angle was 16.4-28.5 degrees (mean, 18.6 degrees ). The erythrocyte sedimentation rate was 28-105 mm/1 hour (mean, 61 mm/1 hour). All patients received 4-drug antituberculosis therapy. RESULTS: All patients underwent the operation successfully and all incisions healed at stage I, without relevant complication. All patients were followed up 14-70 months (mean, 25.6 months). All symptoms of tuberculosis disappeared and the erythrocyte sedimentation rate returned to normal. At last follow-up, Frankel classification was returned to E from D in 3 cases, returned to D from C in 1 case. Two cases suffered from pains in the lumbosacral region and at the donor site, 1 case suffered from upper abdominal discomfort and poor appetite,but these symptoms disappeared after symptomatic treatment. At last follow-up, X-ray examination indicated that the lumbosacral angle was 23.4-34.2 degrees (mean, 28.6 degrees ). According to Bridwell criteria, 5 cases gained grade I bone fusion, and 2 cases gained grade II bone fusion, without migration of bone graft, or loosening or breakage of titanium plate or bolt. CONCLUSIONS: Stage I anterior approach debridement and autologous iliac crest graft with single self-locked titanium plate internal fixation is safe and effective in treating lumbosacral tuberculosis. It can achieve good bone fusion and stable lumbosacral stability, and maintain good deformity correction. PMID- 29786302 TI - [Duckett URETHROPLASTY-URETHROTOMY FOR STAGED HYPOSPADIAS REPAIR]. AB - OBJECTIVE: To explore the surgical outcome of Duckett urethroplasty-urethrotomy for staged hypospadias repair. METHODS: Fifty-three patients with hypospadias were treated by 2 stages between August 2013 and September 2014. The age ranged from 10 months to 24 years and 3 months (median, 1 year and 10 months). There were 5 cases of proximal penile type, 2 cases of penoscrotal type, 36 cases of scrotal type, and 10 cases of perineal type. Urethroplasty was performed with tubed transverse preputial island flap only in 27 cases or combined with urethral plate in the other 26 cases, thus a urethrocutaneous fistula was intentionally created; stage II fistula repair was carried out at 1 year after stage I repair. RESULTS: The length of the new urethra ranged from 2 to 8 cm with an average of 3.6 cm. The patients were followed up 5-17 months with an average of 8 months after stage II repair. After stage I repair, urethral fistula was noted at other site in 3 cases, skin necrosis in 1 case, glandular stricture in 2 cases, cicatric curvature in 1 case, and position and morphology of urethral orifice not ideal in 4 cases. After stage II repair, urethral fistula was noted in 2 cases, mild urethral diverticulum in 2 cases, and stricture at temporary repair site in 1 case. HOSE score was 12-16 at 3 months after stage II repair (mean, 14.5). At 3 14 months after stage II repair, the maximum flow rate ranged from 3.9 to 22.7 mL/s with an average of 8.6 mL/s. CONCLUSIONS: Duckett urethroplasty-urethrotomy can be used as staged repair for primary treatment of hypospadias because of high safety, low complication incidence, and satisfactory appearance. PMID- 29786301 TI - [OBSERVATION OF EFFECTIVENESS OF THORACOSCOPIC SURGERY FOR LATEPRESENTING CONGENITAL DIAPHRAGMATIC HERNIA]. AB - OBJECTIVE: To explore the effectiveness of thoracoscopic surgery for treating late-presenting congenital diaphragmatic hernias and summarize the experience. METHODS: Between October 2012 and February 2015, 21 children with late-presenting congenital diaphragmatic hernias underwent thoracoscopic surgery. Of the 21 cases, 12 were girls and 9 were boys with a median age of 1 year and 3 months (range, 2 months to 8 years). Eight patients had obvious symptom in the initial stage:shortness of breath and dyspnea; 13 cases were found occasionally through chest radiography. Of 21 cases, 17 had left diaphragmatic hernias and 4 had right diaphragmatic hernias. The emergency surgery was performed in 5 cases because oppressed obviously and selective operation in 16 cases. Hernial sac existed in 5 cases; there were 19 cases of Bochdalek's hernia and 2 cases of Morgagni's hernia. The size of diaphragmatic defect ranged from 3 cm*2 cm to 5 cm*5 cm. RESULTS: The operation time was 35-80 minutes (mean, 50 minutes), and intraoperative blood loss was 3-5 mL (mean, 3.8 mL). Primary healing of incision was obtained. Postoperative abdominal distension and pneumothorax occurred in 12 and 2 cases respectively. The follow-up time was 1-3 years (mean, 20 months). All the cases had a good recovery and satisfactory appearance of the thoracic incision. The symptoms and signs of shortness of breath and dyspnea disappeared. There was no recurrence and chest infection. CONCLUSIONS: Under the conditions of mastering operative indications strictly, thoracoscopic repair for late presenting congenital diaphragmatic hernia is safe and feasible. It can facilitate the procedure and decrease the recurrence rate relying on intraoperative application of hernia repair needle, knot pusher-assistant, and reasonable processing defect periphery. PMID- 29786303 TI - [EFFECTIVENESS EVALUATION OF THORACIC ENDOVASCULAR AORTIC REPAIR FOR BLUNT THORACIC AORTIC INJURY WITH HOSTILE STENT-GRAFT PROXIMAL LANDING ZONE]. AB - OBJECTIVE: To explore the effectiveness of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) with hostile stent-graft proximal landing zone. METHODS: A retrospective analysis was made on the clinical data of 13 patients with BTAI with hostile stent-graft proximal landing zone treated by TEVAR between December 2007 and December 2014. There were 10 males and 3 females with the mean age of 44 years (range, 24-64 years). The imaging examination indicated Stanford type B aortic dissection in 7 cases, pseudoaneurysm in 3 cases, aneurysm in 1 case, and penetrating ulcer in 2 cases. According to the partition method of thoracic aortic lesion by Mitchell, 8 cases underwent stent graft with left subclavian artery (LSA) coverage, 3 underwent chimney stents for LSA, and 2 for left common carotid artery (LCCA). In 2 cases receiving chimney TEVAR involving LCCA, one underwent steel coils at the proximal segment of LSA to avoid type II endoleak and the other underwent in situ fenestration for endovascular reconstruction of LSA. RESULTS: All TEVAR procedures were successfully performed. The mean operation time was 1.8 hours (range, 1-3 hours); the mean intraoperative blood loss was 120 mL (range, 30-200 mL); and the mean hospitalization time was 15 days (range, 7-37 days). No perioperative death and paraplegia occurred. The patients were followed up 3-30 months (mean, 18 months). Type I endoleak occurred in 1 case during operation and spontaneously healed within 6 months. Hematoma at brachial puncture site with median nerve compression symptoms occurred in 1 case at 3 weeks after operation; ultrasound examination showed brachial artery pseudoaneurysm and thrombosis, and satisfactory recovery was obtained after pseudoaneurysmectomy. No obvious chest pain, shortness of breath, left upper limbs weakness, numbness, and dizziness symptoms were observed. Imaging examination revealed that stentgraft and branched stent remained in stable condition. Meanwhile the blood flow was unobstructed. No lesions expanded and ruptured. No new death, bacterial infection, or other serious complications occurred. CONCLUSIONS: According to Mitchell method, individualized plan may be the key to a promising result. More patients and further follow-up need to be included, studied, and observed. PMID- 29786304 TI - [ANTERIOR SUBCUTANEOUS TRANSPOSITION OF ULNAR NERVE AND HAND INTRINSIC MUSCLES FUNCTION RECONSTRUCTION FOR SEVERE CUBITAL TUNNEL SYNDROME]. AB - OBJECTIVE: To study the effectiveness of anterior subcutaneous transposition of ulnar nerve with reconstruction of hand intrinsic muscle in the treatment of severe cubital tunnel syndrome. METHODS: Between March 2006 and May 2015, 22 cases (23 hands) of severe cubital tunnel syndrome were treated by use of anterior subcutaneous transposition of ulnar nerve with reconstruction of hand intrinsic muscle. There were 15 males and 7 females, aged 45-60 years (mean, 55 years). The causes were valgus deformity of elbow joint in 12 cases, ulnar nerve subluxation in 4 cases, and osteoarthritis in 6 cases. The disease duration was 10 months to 3 years (mean, 17 months). According to Akahori classification, 14 cases were rated as type 4 and 9 cases as type 5. The ring/little finger's numbness, hand intrinsic muscle atrophy, recovery of thumb adduction function, and improvement of claw hand deformity were observed after operation. Thumb and index finger's pinch strength was measured by use of pinch device; postoperative hand function was evaluated by the standards of Chinese Medical Society of Hand Surgery of upper limb assessment protocol. RESULTS: All incisions healed well and all cases were successfully followed up 8 to 24 months (mean, 14 months). Numbness of ring/little finger was significantly reduced at 1 day after operation in 10 hands; numbness disappeared completely at 1 month after operation in 12 hands; mild numbness remained at 14 months after operation in 11 hands. At last follow-up, hand intrinsic muscle atrophy partially improved (+++) in 1 hand, no improvement in 22 hands; improvement of claw hand deformity was achieved in 17 hands, no improvement in 6 hands; pinch strength of thumb and index finger was significantly improved to (5.07+/-1.11) kg from preoperative (2.91+/-0.63) kg (t= 12.340, P=0.032). At last follow-up, the results were excellent in 11 hands, good in 8 hands, fair in 3 hands, and poor in 1 hand, and the excellent and good rate was 82.6%. CONCLUSIONS: Anterior subcutaneous transposition of ulnar nerve with reconstruction of hand intrinsic muscle is a simple, effective, and reliable surgical treatment for severe cubital tunnel syndrome. PMID- 29786305 TI - [COMPARISON OF HEALING RESULTS BETWEEN TIBIAL NERVE AND COMMON PERONEAL NERVE AFTER SCIATIC NERVE INJURY REPAIR IN RHESUS MONKEY]. AB - OBJECTIVE: To investigate the regularity of myelin degeneration and regeneration and the difference of axonal density between tibial nerve and common peroneal nerve after sciatic nerve injury repair in rhesue monkey. METHODS: Nine adult rhesue monkeys (male or female, weighing 3.5-4.5 kg) were selected to establish the model of rat sciatic nerve transaction injury. The tibial nerve and common peroneal nerve of 5 mm in length were harvested at 5 mm from injury site as controls in 3 monkeys; the distal tibial nerve and common peroneal nerve were repaired with 9-0 suture immediately in the other 6 monkeys. And the gross observation and neural electrophysiological examination were performed at 3 and 8 weeks after repair respectively. Then, distal tibial nerve and common peroneal nerve at anastomotic site were harvested to observe the myelin sheath changes, and to calculate the number of axon counts and axonal density by staining with Luxol Fast Blue. RESULTS: Atrophy of the lower limb muscle and various degrees of plantar ulcer were observed. Gross observation showed nerve enlargement at anastomosis site, the peripheral connective tissue hyperplasia, and obvious adhesion. The compound muscle action potential (CMAP) of tibial nerve and common peroneal nerve could not be detected at 3 weeks; the CMAP amplitude of common peroneal nerve was less than that of the tibial nerve at 8 weeks. Different degrees of axonal degeneration was shown in the tibial nerve and common peroneal nerve, especially in the common peroneal nerve. The average axonal density of common peroneal nerve was lower than that of tibial nerve at 3 weeks (13.2% vs. 44.5%) and at 8 weeks (10.3% vs. 35.3%) after repair. CONCLUSIONS: The regeneration of tibial nerve is better and faster than that of common peroneal nerve, and gastrocnemius muscle CMAP recovers quicker, and amplitude is higher, which is the reason of better recovery of tibial nerve. PMID- 29786306 TI - [EFFECT OF PASSIVE MOVEMENT ON EXPRESSION OF miRNA-1 AND DIFFERENTIATION OF MYOBLASTS IN DENERVATION-INDUCED SKELETAL MUSCLE ATROPHY IN RATS]. AB - OBJECTIVE: To investigate the expression of miRNA-1 in denervated skeletal muscle at different periods, and to explore effects of passive movement on the expression of miRNA-1 and differentiation of myoblasts in denervation-induced skeletal muscle atrophy in rats. METHODS: Twenty-seven Sprague Dawley rats, weighing (200+/-10) g, were randomly divided into sham-operated group (group A, n=3), denervated group (group B, n=12), and passive movement group (group C, n=12). After the right sciatic nerve was exposed and dissociated, the sciatic nerve of 1 cm in length was removed in groups B and C; resection was not performed in group A. At 1 day after operation, passive flexion and extension movement was performed on the right hind limb in group C. At 6 hours in group A and at 3, 7, 14, and 28 days in groups B and C, 3 rats were sacrificed to measure the wet weight ratio of gastrocnemius muscle, to observe the diameter of the gastrocnemius muscle cell and evaluate the muscle atrophy by HE staining; RT-PCR was used to detect the mRNA expression of miRNA-1 and myocyte differentiation factor (MyoD), and immunohistochemistry to determine the protein expression of MyoD. RESULTS: Atrophy in various degrees was observed in denervated gastrocnemius muscle of groups B and C. The muscle fiber arranged in disorder and the diameter of the muscle cells decreased gradually with the time, without normal structure and morphology. The wet weight ratio and the cell diameter of the gastrocnemius in groups B and C were significantly less than those in group A (P<0.05); the wet weight ratio at 7, 14, 28 days and the cell diameter at 7, 14 days of group B were significantly greater than those of group A (P<0.05). The expressions of miRNA-1 and MyoD mRNA gradually increased with time in groups B and C, but were significantly less than those of group A at each time point (P<0.05). At 7, 14, and 28 days after operation, the expressions of miRNA-1 and MyoD mRNA in group C were significantly higher than those in group B (P<0.05). Immunohistochemical staining showed positive expression of MyoD in groups A, B, and C at each time point, but higher expression was observed in groups B and C than group A; the expression increased with time in groups B and C, and it was significantly higher in group C than group B. The correlation analysis results showed that the overall change trend of miRNA-1 and MyoD had no relation with the gastrocnemius wet weight ratio at 3 and 7 days (P>0.05), and had positive correlation at 14 and 28 days (P<0.05); positive correlation was found between the relative expression of MyoD and miRNA-1 mRNA (P<0.05). CONCLUSIONS: Passive movement can prevent amyotrophy by increasing the expression of miRNA-1 and promoting the differentiation of myoblasts. PMID- 29786307 TI - [EFFECT OF HUMAN PLACENTAL DECIDUA BASALIS DERIVED MESENCHYMAL STEM CELLS IN REPAIR OF NUDE MICE SKIN WOUND]. AB - OBJECTIVE: To investigate the effectiveness of human placental decidua basalis derived mesenchymal stem cells (PDB-MSCs) in repairing full-thickness skin defect of nude mice. METHODS: Human placenta samples were obtained from healthy donor mothers with written informed consent. PDB-MSCs were isolated through enzymic digestion and density gradient centrifugation; the 4th passage cells were identified by cellular morphology, cell adipogenic and osteogenic differentiation, and phenotype evaluation. Forty-two 4-5-week-old BALB/c female nude mice were randomly divided into experimental group (n=21) and control group (n=21). The 4th passage PDB-MSCs solution (200 MUL, 5*106/mL) was injected into the mice of experimental group via caudal vein; the mice of control group were given equal volume of PBS. The full-thickness skin defect model of 1.5 cm*1.5 cm in size was made after 3 days. The wound healing was observed generally at 1, 2, 4, 7, 14, 18, 21, 25, and 30 days after operation, and the wound healing rate was calculated after wound decrustation. HE staining was used to observe the wound repair at 1, 7, 14, 21, and 31 days; immunofluorescent staining was used for cellular localization at 7, 14, and 31 days after operation. RESULTS: Cells isolated from human placenta were MSCs which had multipotential differentiation ability and expressed MSCs phenotype. Animals survived to the end of the experiment. The general observation showed that the experimental group had a faster skin repairing speed than the control group; the time for decrustation was 12-14 days in experimental group and was 14-17 days after operation in the control group. The wound healing rate of experimental group was significantly higher than that of control group at 14, 18, and 21 days (t=4.001, P=0.016; t=3.380, P=0.028; t=3.888, P=0.018), but no significance was found at 25 and 30 days (t=1.565, P=0.193; t=1.000, P=0.423). HE staining showed lower inflammatory reaction, and better regeneration of the whole skin and glands with time in the experimental group. The immunofluorescent staining was positive in skin defect area of experimental group at different time points which displayed that human PDB-MSCs existed. CONCLUSIONS: Through enzymic digestion and density gradient centrifugation, PDB-MSCs can be obtained. Pre-stored PDB-MSCs can mobilize to the defect area and participate in repair of nude mice skin. PMID- 29786308 TI - [EXPERIMENTAL STUDY ON BONE DEFECT REPAIR WITH COMPOSITE OF ATTAPULGITE/COLLAGEN TYPE I/POLY (CAPROLACTONE) IN RABBITS]. AB - OBJECTIVE: To investigate the effect of repairing radial bone defect with scaffold material of attapulgite/collagen type I/poly (caprolactone) (ATP/Col I/PCL) in rabbits and the possibility as bone graft substitutes. METHODS: ATP/Col I/PCL materials were prepared via adding ATP to hexafluoroisopropanol after dissolved Col I/PCL (3:2), and Col I/PCL materials via dissolving Col I/PCL (3:2) in hexafluoroisopropanol served as control. The structure of scaffolds was observed under scanning electron microscope (SEM). Twenty-four Japanese white rabbits (male, 2 months old) were used to establish the bilateral radius defect model of 15 mm in length, and randomly divided into group A (6 rabbits, 12 defects), group B (9 rabbits, 18 defects), and group C (9 rabbits, 18 defects); then the Col I/PCL scaffold was implanted in the bone defect area in group B, the ATP/Col I/PCL scaffold in group C, no treatment was done in group A as control. The general condition of rabbits was observed after operation, and bone defect repair was evaluated by X-ray at 4, 8, and 12 weeks. At 12 weeks, the tissue of defect area was harvested for the general, SEM, Micro-CT, histological, and immunohistochemical staining to observe defect repair and material degradation. RESULTS: SEM observation showed that two kinds of materials were porous structure, ATP/Col I/PCL structure was more dense than Col I/PCL. All animals survived to the end of experiment, and no incision infection occurred during repair process.X-ray films showed that the bone marrow cavity was re-opened in defect area of group C with time, the repair effect was superior to that of groups A and B. At 12 weeks after operation, general observation showed that scaffold material had good fusion with the surrounding tissue in groups B and C, defect was filled with connective tissue in group A. SEM indicated that the surface and pore of the scaffold were covered with a large number of cells and tissues in groups B and C. Micro-CT demonstrated that the new bone volume, bone mineral content, tissue mineral content, and connectivity density of group C were significantly higher than those of groups A and B (P<0.05). The observation of histology and immunohistochemical staining indicated that there were lots of connective tissues in defect area of group A, and ALP, Col I, and OPN were weakly expressed; there were many collagen fibers in scaffold degradation area in group B, and the expression levels of ALP, Col I, and OPN were higher than those of group A; there was few new bone in group C, the degradation rate of the scaffold was slower than that of group B, and the expression of Col I and OPN were enhanced, while ALP was weakened when compared with groups A and B. CONCLUSIONS: ATP/Col I/PCL composite scaffold material can degrade in vivo, and has dense three-dimensional porous structure, good biocompatibility, and high potentiality of bone repair, so it can be used as bone substitute material. PMID- 29786309 TI - [EXPERIMENTAL STUDIES ON EFFECTS OF SALIDROSIDE/COLLAGEN/ POLYCAPROLACTONE NERVE GUIDE CONDUITS FOR REPAIRING SCIATIC NERVE DEFECT IN RATS]. AB - OBJECTIVE: To fabricate salidroside/collagen/polycaprolactone (PCL) nerve conduit composite and to investigate the effect of composite nerve conduits for repairing sciatic nerve defect. METHODS: The salidroside microspheres were prepared by W/O/W method, and the sustained release rate of microspheres was detected. The microspheres containing 10, 20, and 40 MUg salidroside were mixed with collagen to prepare the nerve conduit core layer by freeze-drying method. The shell layer of collagen/PCL scaffold material was fabricated by electrospinning technology. The genipin cross-linked salidroside/collagen/PCL nerve conduit composite was prepared. The structure of nerve conduit was observed before and after cross linked by scanning electron microscope. Thirty-eight Wistar rats were used to make the right sciatic nerve defect model of 15 mm in length, and randomly divided into groups A, B, C, D (n=9), and group E (n=2), then defect was repaired with the collagen/PCL conduit in group A, autologous nerve in group E, the 10, 20, and 40 MUg/mL salidroside/collagen/PCL conduit in groups B, C, and D, respectively. The survival of rats was observed. The sciatic functional index (SFI) was evaluated at 1, 3, and 6 months after operation. At 6 months, the tissue of defect area was harvested for the general, electrophysiology, histological, and immunohistochemical[S-100 and peripheral myelin protein 0(P0)] staining observations. RESULTS: Salidroside microspheres showed burst release at 3 days, and then it tended to be stable at 13 days and lasted for 16 days, with a cumulative release rate of 76.59%. SEM showed that the disordered fiber of nerve conduit shell layer after crosslinking became conglutination, shrinkage, and density, and had void. The channels of core layer were clearly visible before and after crosslinking. The rats had no infection or death after operation. The SFI of group E was significantly higher than that of groups A, B, C, and D at 1, 3, and 6 months (P<0.05); it was significantly higher in groups B, C, and D than group A (P<0.05), but no significant difference was found among groups B, C, and D at 1 month (P>0.05); there was no significant difference in SFI among groups A, B, C, and D at 3 months (P>0.05); SFI was significantly higher in group C than groups A, B, and D and in groups A and B than group D (P<0.05), but no significant difference between groups A and B (P>0.05) at 6 months. In addition, no significant difference was shown among different time points in the other groups (P>0.05) except groups C and E at 1, 3, and 6 months (P<0.05). The general observation showed that good connection with the thick nerve in groups B and C, and connection with the fine nerves in groups A and D. The conduit materials obviously degraded. Nerve electrophysiological examination showed that the latency/conduction velocity of groups C and E were significantly lower than those of groups A, B, and D (P<0.05), but difference was not significant between groups C and E, and among groups A, B, and D (P>0.05). The histological observation showed that the nerve fiber tissue of groups B, C, and E was obviously more than that of groups A and D, and group C was similar to group E in the nerve fiber arrangement, and the core layer material of each group was completely degraded. Immunohistochemical staining showed that S-100 and P0 proteins expressed in all groups; and the expression level of groups B, C, and E was significantly higher than that of groups A and D, and gradually increased (P<0.05); difference in S 100 expression level was not significant between groups A and D (P>0.05), and P0 expression level of group A was significantly lower than that of group D (P<0.05). CONCLUSIONS: Salidroside/collagen/PCL nerve conduit can promote sciatic nerve defect repair. PMID- 29786310 TI - [ROLE OF Smad4 ON FIBROSIS OF TENDON DERIVED FIBROBLASTS INDUCED BY TRANSFORMING GROWTH FACTOR beta1 BY TARGETED REGULATION OF miRNA219-5P]. AB - OBJECTIVE: To investigate the effect of Smad4 on the fibrosis of tendon derived fibroblasts (TDFs) induced by transforming growth factor beta1(TGF-beta1) by targeted regulation of miRNA219-5P (miR219-5P). METHODS: The tendons donated by the volunteers were harvested to isolate and culture TDFs. The 3rd generation cells were used for experiment. Chemically synthesized miR219-5P mimics, miR219 5P inhibitor, and negative control sequences were transfected into TDFs. The gene expression of miR219-5P in TDFs was detected by real-time PCR, and the protein expression of Smad4 in TDFs was detected by Western blot at 48 hours after transfection. The combining sites of miR219-5P and Smad4 in 3'UTR district were predicted by informatics software. Wild type and mutant type reporter gene expression vectors were constructed and then targeted verification was carried out by the luciferase reporter gene test. Transfected TDFs were then induced by TGF-beta1. The proliferation activity of the cells were measured by the cell counting kit 8 after culturing for 24, 48, and 72 hours. The expressions of fibrosis related proteins in TDFs were detected by Western blot at 72 hours. RESULTS: After TDFs were transfected by miR219-5P mimics, miR219-5P expression was significantly up-regulated, but the expressions of Smad4 was decreased subsequently (P<0.05). Intracellular expression of miR219-5P was inhibited by miR219-5P mimics inhibitor, however, the protein expression of Smad4 was significantly increased (P<0.05). Luciferase reporter gene test showed that luciferase activities were significantly decreased in pGL3-WT-Smad4+mimics group, but were significantly increased in pGL3-WT-Smad4+inhibitor group when compared with pGL3-WT-Smad4 transfected group (P<0.05), but no significant difference was found between GL3-MT-Smad4+mimics and pGL3-MT-Smad4+inhibitor groups (P>0.05). Cell proliferation and the fibrosis related proteins were increased in TGF-beta1 induced TDFs, however, decreased in TGF-beta1 induced TDFs after transfected by miR219-5P inhibitor (P<0.01). CONCLUSIONS: miR219-5P can significantly inhibit fibrosis of TDFs induced by TGF-beta1 by down-regulating Smad4 expression. PMID- 29786311 TI - [RESEARCH PROGRESS IN LOWER LIMB LENGTHENING BY INTRAMEDULLARY NAIL]. AB - OBJECTIVE: To summarize the research progress in the lower limb lengthening by intramedullary nail. METHODS: The domestic and foreign related literature about the lower limb lengthening by intramedullary nail was reviewed, summarized, and analyzed. RESULTS: The intramedullary nail lengthening systems can be divided into 3 types:distraction by mechanical strength, by motorized electronic power, or by motorized magnetic force. The new technology has obvious advantages in complication incidence, limb function, bone healing rate, comfortable and cosmetic degree of the patients, and hospitalization days compared with the external fixation, but it also has the disadvantages including lengthening failure of system breakdown, intramedullary infection, injuries of vessel and nerve, limited distraction length, and expensive price of the apparatus. And the method also has several contraindications:narrow medulla, multiple curves of medulla, osteomyelitis, skin infection, and unclosed epiphyseal plate. CONCLUSIONS: The lower limb lengthening by intramedullary nail is a major improvement of Ilizarov technology. Although the method has been used in limited cases, the preliminary clinical results are excellent, and it can be regarded as a new trend of the limb lengthening, bone reconstruction, and deformity correction. PMID- 29786312 TI - [Minimally invasive osteosynthesis using helical plate for complex humeral shaft fractures involved proximal metaphysis]. AB - OBJECTIVE: To evaluate the effectiveness of minimally invasive osteosynthesis using the helical plate for complex humeral shaft fractures involved proximal metaphysis, and to explore its feasibility and security. METHODS: A retrospective analysis was made on the clinical data of 16 patients with complex humeral shaft fractures involved proximal metaphysis who underwent minimally invasive osteosynthesis with the helical plate between December 2009 and May 2015. There were 11 males and 5 females, aged from 18 to 56 years (mean, 34.6 years). The causes of fracture included falling injury in 5 cases, falling injury from height in 3 cases, traffic accident injury in 4 cases, sports injury in 3 cases, and belts twisted injury in 1 case. Accroding to Orthopaedic Trauma Association (OTA) classifications, 6 cases were rated as type 12-C1, 3 cases as type 12-C2, and 7 cases as type 12-C3. The time between injury and operation was 2-13 days (mean, 7.2 days). The operation time, intraoperative blood loss, complications, union time were recorded, the functional outcome of the elbow joint was evaluated by Mayo elbow performance score, and the function of the shoulder was assessed by the University of California at Los Angeles (UCLA) shoulder rating scale. RESULTS: The mean operation time was 92 minutes (range, 51-127 minutes), and the mean intraoperative blood loss was 212 mL (range, 100-450 mL). All incisions healed by first intention without neurologic complications or wound infection. All patients were followed up 8-28 months (mean, 16.6 months), and bony union was obtained at 13-36 weeks (mean, 19.2 weeks). No loosening or breakage of internal fixation occurred. The Mayo elbow performance score was 90-100 (mean, 99), and the UCLA shoulder rating scale was 31-35 (mean, 34.6). CONCLUSIONS: The technique of minimally invasive osteosynthesis using the helical plate is safe and feasible for humeral shaft fracture, especially for complex humeral shaft fractures involved proximal metaphysis, and it has the advantages of minimal invasion and low risk for iatrogenic nerve injury and satisfactory effectiveness. PMID- 29786313 TI - [A biomechanical study on reconstruction of forearm interosseous membrane using extensor carpi radialis longus combined with radial head replacement for restoring forearm longitudinal stability]. AB - OBJECTIVE: To evaluate the effect of reconstruction of forearm interosseous membrane (IOM) using extensor carpi radialis longus combined with radial head replacement for restoring the forearm longitudinal stability. METHODS: Ten fresh frozen adult cadaveric forearms were selected, including 8 males and 2 females with a mean age of 38.2 years (range, 29-74 years). Each forearm was treated as following steps: radial head excision (group A), radial head excision+the distal ulnar radial joints separation (group B), radial head excision+the distal ulnar radial joints separation+IOM central band excision (group C), reconstructed IOM with extensor carpi radialis longus tendon (group D), radial head prothesis replacement (group E), and reconstructed IOM with extensor carpi radialis longus tendon+radial head prothesis replacement (group F). The distance between ulna and radius and radioulnar joint displacement were observed under load and non load. The force loading on both ends of specimen was recorded when the radius shifted 5 mm proximally. RESULTS: Restoring the radial length could maintain normal distance between radius and ulna. The interosseous membrance reconstruction could restore the load transmission between radius and ulna. The force loading specimen was (74.507+/-4.967), (49.227+/-1.940), (17.827+/-1.496), (24.561+/-1.390), (140.247+/-8.029), and (158.423+/-9.142)N in groups A, B, C, D, E, and F respectively when the radius shifted 5 mm proximally, showing significant difference among groups (P<0.01). CONCLUSIONS: Reconstruction of the IOM with the extensor carpi radialis longus tendon is insufficient to restore the forearm longitudinal stability. Reconstruction using extensor carpi radialis longus tendon combined with radial head replacement may be a new choice for treatment of forearm longitudinal instability. PMID- 29786314 TI - [Strategies of closed reduction in treatment of femoral neck fracture using cannulated screw fixation]. AB - OBJECTIVE: To study intraoperative reduction strategy in treatment of femoral neck fracture using cannulated screw fixation and the relationship between excellent and good rate of reduction and postoperative effectiveness. METHODS: A retrospective analysis was made on the clinical data of 174 cases of femoral neck fracture treated between August 2005 and March 2015. There were 78 males and 96 females with an average age of 53.8 years (range, 23-75 years). The injury causes were falling in 85 cases, traffic accident in 61 cases, and falling from height in 28 cases. According to Garden typing, there were 35 cases of type I, 56 cases of type II, 47 cases of type III, and 36 cases of type IV. The time from injury to operation was 1-7 days (mean, 2.74 days). Based on reduction strategy, closed 3 hollow compression screws were used; evaluating standards for fracture reduction effect were also established. Harris score was used for effectiveness evaluation. RESULTS: All the cases received follow-up of 12-42 months (mean, 36.5 months). Bone healing was obtained in 152 cases at 6-12 months (mean, 9 months). Non-union and internal fixation failure occurred in 9 and 3 patients respectively, who underwent hemiarthroplasty; femoral head necrosis occurred in 6 patients after removing internal fixator at 15-26 months (mean, 18.5 months) after operation, who underwent total hip arthroplasty; 4 patients with non-union received vascular pedicle iliac flap transplantation. No other serious complications were observed. At last follow-up, the excellent and good rate of reduction was 94.29% for Garden type I, 91.07% for type II, 87.23% for type III, and 75.00% for type IV, with a total excellent and good rate of 87.36%; the excellent and good rate of Harris score was 97.14% for Garden type I, 78.57% for type II, 68.09% for type III, and 50.00% for type IV, with a total excellent and good rate of 73.56%. CONCLUSIONS: To obtain high Harris score in fixation of femoral neck fractures by using hollow screws, surgeons not only need reasonable technology, but also follow correct and good reduction strategy and assessment,fracture complexity is inversely proportional to excellent and good rate of reduction. Higher excellent and good reduction rate of complexity fracture should be obtained as much as possible in order to achieve good prognosis. PMID- 29786315 TI - [Effect of three-dimensional printing navigation templates assisting reconstruction with personalized unrestricted total knee prosthesis for treating maliganant bone tumors around knees]. AB - OBJECTIVE: ?To evaluate the effectiveness of three-dimensional (3D) printing navigation templates assisting reconstruction with personalized unrestricted total knee prosthesis to treat maliganant bone tumors around the knee. METHODS: ?Between March 2007 and September 2014, 43 patients with malignant tumor around the knee were divided into 2 groups: 3D printing navigation templates assisting reconstruction with personalized unrestricted total knee prosthesis were used in 21 cases (trial group), and conventional tumor resection and reconstruction with hinged total knee prosthesis were used in 22 cases (control group). There was no significant difference in age, gender, tumor location, pathological diagnosis, tumor stage, diameter of tumor, disease duration, and preoperative visual analogue scale (VAS) score between 2 groups (P>0.05), which were comparable. Intraoperative length of tumor resection and blood loss were recorded and compared, and the postoperative complications and tumor recurrence were observed. The Musculoskeletal Tumor Society (MSTS) score was used to evaluate knee joint function. RESULTS: ?The operations were completed successfully in the patients of 2 groups and postoperative pathological results were negative in tumor resection margin. All the patients were followed up 12-77 months (mean, 36.7 months). There was no significant difference in the length of tumor resection and blood loss between trial group and control group (t=1.01, P=0.32; t=-0.76, P=0.45). In trial group, the resection range and reconstruction results were consistent with preoperative computer simulation; postoperative complications happened in 2 cases (9.52%); 1 case of immunological rejection and 1 case of infection); 2 cases (9.52%) had recurrence of osteosarcoma and pulmonary metastasis at 1 year after operation. In the control group, complication occurred in 6 cases (27.27%; 2 cases of periprosthetic fractures, 2 cases of infection, 1 case of incision nonunion, and 1 case of common peroneal nerve injury); 4 cases (18.18%) had recurrence of osteosarcoma and metastasis at 1 year after operation. There was no significant difference in postoperative complication and recurrence rate between 2 groups (chi2=2.24, P=0.14; chi2=0.67, P=0.41). At last follow-up, distal femur score of tumor and proximal tibial score of tumor in trial group were significantly better than those in control group (t=4.89, P=0.00; t=3.94, P=0.00). The mean flexion and extension range of motion of the knee joint was (115.45+/-12.25) degrees in trial group and was (101.49+/-11.96) degrees in control group, showing significant difference (t=3.78, P=0.00). CONCLUSIONS: ?The effectiveness using 3D printing navigation templates assisting reconstruction with personalized unrestricted prosthesis for maliganant bone tumors around the knee is better than conventional tumor resection and reconstruction with hinged total knee prosthesis. It can improve the joint function better and the patients' quality of life. PMID- 29786316 TI - [Arthroscopic treatment of both anterior and posterior cruciate ligament tibial insertion avulsion fractures with suture and absorbable screw double fixation]. AB - OBJECTIVE: ?To evaluate the effectiveness of arthroscopic suture and absorbable screw double fixation for both anterior and posterior cruciate ligament avulsion fractures of tibial insertions. METHODS: ?Between June 2006 and September 2013, 8 patients with anterior and posterior cruciate ligament avulsion fractures of the tibial eminence underwent arthroscopic treatment with suture and absorbable screw double fixation. There were 5 males and 3 females, with a mean age of 28.9 years (range, 18-43 years). The causes of injury included traffic accident in 5 cases and falling from height in 3 cases. The time from injury to operation was 3-10 days (mean, 6.2 days). The Lysholm knee score, International Knee Documentation Committee (IKDC) score, and Tegner rating scales were used to evaluated the knee function. RESULTS: ?Primary healing of incision was obtained, without infection or deep vein thrombosis. The mean follow-up period was 42.4 months (range, 24 to 65 months). At 3 months after operation, X-ray films showed good reduction and healing of fracture. The anterior and posterior drawer tests were negative. The knee range of motion was normal (0-125 degrees ), and it recovered to preoperative level in 7 cases. The IKDC score, Tegner score, and Lysholm score were significantly improved to 90.4+/-5.2, 7.5+/-1.6, and 89.2+/-3.5 from preoperative 52.1+/-3.3, 3.3+/-1.0, and 51.9+/-3.5 respectively (t=-38.680, P=0.000; t=-39.520, P=0.000; t=-41.150, P=0.000). CONCLUSIONS: ?A combined injury of anterior and posterior cruciate ligament avulsion fractures of tibial insertions is rare. Arthroscopic treatment with suture and absorbable screw double fixation is a useful technique to restore tibial avulsion injuries with well-documented radiographic healing, good clinical outcomes, and low complication rates. PMID- 29786317 TI - [Effect of distal tibial varus and valgus deformity on joint contact]. AB - OBJECTIVE: ?To study the effect of different degrees of distal tibial varus and valgus deformities on the tibiotalar joint contact, and to understand the role of fibular osteotomy. METHODS: ?Eight cadaveric lower legs were used for biomechanical study. Nine conditions were included: normal ankle joint (group A), 10 degrees varus (group B), 5 degrees varus (group C), 5 degrees valgus (group D), 10 degrees valgus (group E) with fibular preserved, and 10 degrees varus (group F), 5 degrees varus (group G), 5 degrees valgus (group H), and 10 degrees valgus (group I) after fibular osteotomy. The joint contact area, contact pressure, and peak pressure were tested; and the translation of contact force center was observed. RESULTS: ?The joint contact area, contact pressure, and peak pressure had no significant difference between group A and groups B to E (P>0.05). After fibular osteotomy, the contact area decreased significantly in groups F and I when compared with group A (P<0.05); the contact pressure increased significantly in groups F, H, and I when compared with group A (P<0.05); the peak pressure increased significantly in groups F and I when compared with group A (P<0.05). There were two main anterior-lateral and anterior medial contact centers in normal tibiotalar joint, respectively; and the force center was in anterior-lateral part, just near the center of tibiotalar joint. While the fibula was preserved, the force center transferred laterally with increased varus angles; and the force center transferred medially with increased valgus angles. However, the force center transferred oppositely to the medial part with increased varus angles, and laterally with increased valgus angles after fibular osteotomy. CONCLUSIONS: ?Fibular osteotomy facilitates the tibiotalar contact pressure translation, and is helpful for ankle joint realignment in suitable cases. PMID- 29786318 TI - [Sinus tarsi approach combined with medial distraction technique for treatment of intra-articular calcaneus fractures]. AB - OBJECTIVE: ?To discuss the effectiveness of limited open reduction via sinus tarsi approach using medial distraction technique in the treatment of intra articular calcaneus fractures by comparing with open reduction and internal fixation via extensile L-shaped incision. METHODS: ?A retrospective analysis was made on the clinical data of 21 patients with intra-articular calcaneus fractures treated by sinus tarsi approach combined with medial distraction technique between April 2013 and November 2014 (minimally invasive group), and 32 patients treated by extensile L-shaped incision approach between June 2012 and September 2014 (extensile incision group). No significant difference was found in gender, age, injury pattern, fracture classification, time from injury to operation, preoperative Bohler angle, Gissane angle, calcaneal varus angle, the ankle and hind-foot score of American Orthopaedic Foot and Ankle Society (AOFAS), and visual analogue scale (VAS) score between 2 groups (P>0.05), which was comparable. The operation time, wound complications, and bone healing time were recorded. The postoperative function was also evaluated by AOFAS score and VAS score. The pre-and post-operative Bohler angle, Gissane angle, and calcaneal varus angle were measured on the X-ray films, and the corrective angle was calculated. RESULTS: ?Sixteen patients were followed up 6-18 months (mean, 11.5 months) in the minimally invasive group, and 23 patients for 6-24 months (mean, 13.5 months) in the extensile incision group. Difference was not significant in operation time between 2 groups (t=0.929, P=0.796). No complication occurred in the minimally invasive group; partial skin flap necrosis occurred in 3 cases of the extensile incision group, was cured after dressing change. There was no loosening of implants or reduction loss in 2 groups at last follow-up. Subtalar joint stiffness occurred in 1 case of the minimally invasive group and 4 cases of the extensile incision group, and 1 patient had discomfort for the implants in the extensile incision group. The bone healing time was (9.9+/-0.8) weeks in the minimally invasive group, and was (10.1+/-0.7) weeks in the extensile incision group, showing no significant difference (t=0.613, P=0.845 ). Bohler angle, Gissane angle, calcaneal varus angle, AOFAS score, and VAS score were significantly improved at last follow-up when compared with preoperative values in 2 groups (P<0.05), but there was no significant difference between 2 groups (P>0.05), and the corrective value of angle showed no significant difference between 2 groups (P>0.05). CONCLUSIONS: ?Limited open reduction via sinus tarsi approach for intra-articular calcaneus fractures could reduce the incidence of wound complications effectively. Meanwhile, the medial distraction technique is helpful to correct the heel varus deformity. PMID- 29786319 TI - [Domestic porous tantalum loaded with bone morphogenetic 7 in repairing osteochondral defect in rabbits]. AB - OBJECTIVE: ?To investigate the ability to repair osteochondral defect and the biocompatibility of porous tantalum loaded with bone morphogenetic protein 7 (BMP 7) by observing the effect of porous tantalum loaded with BMP-7 in repairing articular cartilage and subchondral bone defect. METHODS: ?The cartilage defect models of medial femoral condyle were established in 48 New Zealand white rabbits, which were randomly divided into 3 groups (n=16): porous tantalum material+BMP-7 (group A) and porous tantalum material (group B) were implanted into the right side of the medial femoral condyle; and no material was implanted as control (group C). The general condition of animals was observed after operation, then the specimens were harvested for gross observation, histological observation, and scanning electron microscope (SEM) observation at 4, 8, and 16 weeks after implantation, micro-CT was used to observe the cartilage and bone ingrowth and bone formation around porous tantalum at 16 weeks after implantation. RESULTS: ?No animal died after operation and wound healed well. Gross observation showed that defects of groups A and B were covered with new cartilage with time, but earlier new cartilage formation and better repair were observed in group A than group B, no repair occurred at the site of bone defects, and defect surface was filled with fibrous tissue in group C. Cartilage repair gross score of group A was significantly higher than that of group B at 8 and 16 weeks (P<0.05) but no significant difference was found between groups A and B at 4 weeks (P>0.05). SEM observation showed that the number of new cartilage and osteoblasts increased gradually with time, and the implanted material was gradually covered with the extracellular matrix, and the new bone tissue grew into the pores of the material; the neonatal bone tissue and extracellular matrix secretion of group A were significantly more than those of group B. The toluidine blue staining results showed that new cartilage and bone tissue gradually increased in the porous tantalum interface, and new bone trabecula formed and grew in the pores, the bone and the porous tantalum contact tended to close, and cartilage defect was gradually covered with cartilage like tissue, cartilage tissue and porous tantalum combined more closely in groups A and B at 4, 8 and 16 weeks. New cartilage and bone tissue of group A was more than that of group B. Micro-CT analysis indicated that the bone mineral density, trabecular thickness, trabecular number, and bone volume fraction of group A were significantly higher than those of group B at 16 weeks (P<0.05), but the trabecular bone space was significantly lower than that of group B (P<0.05). CONCLUSIONS: ?The domestic porous tantalum has good biocompatibility, domestic porous tantalum loaded with BMP-7 can promote the formation of a stable connection with the host and has a good effect on cartilage and subchondral bone defect repair. PMID- 29786320 TI - [Therapeutic evaluation of intertransverse bone graft for single segmental thoracic spinal tuberculosis]. AB - OBJECTIVE: ?To explore the effectiveness of intertransverse bone graft after debridement and fusion combined with posterior instrumentation in patients with single segmental thoracic tuberculosis. METHODS: ?Between March 2014 and May 2015, 17 cases of thoracic tuberculosis were treated by the surgery of intertransverse bone graft after debridement and fusion combined with posterior instrumentation. There were 10 males and 7 females with an average age of 48.5 years (range, 18-70 years), and with a mean disease duration of 4 months (range, 1-9 months). The affected segments included T4, 5 in 2 cases, T6, 7 in 5 cases, T7, 8 in 3 cases, T9, 10 in 2 cases, T10, 11 in 4 cases, and T11, 12 in 1 case. The operation time, intraoperative blood loss, and hospitalization time were recorded. Postoperative plain radiography was taken to assess the decompression and internal fixation, and the fusion effect was evaluated by X-ray or CT examination. The erythrocyte sedimentation rate (ESR), C reactive protein (CRP), visual analogue scale (VAS), Oswestry disability index (ODI), and Kyphosis angle were recorded and compared; the nerve function was evaluated by American Spinal Injury Association (ASIA). RESULTS: ?The mean operation time, intraoperative blood loss, and hospitalization time were 184 minutes (range, 165-220 minutes), 231 mL (range, 150-800 mL), and 18 days (range, 12-26 days) respectively. No complication of hematoma or wound dehiscence was found. All patients were followed up 17.9 months on average (range, 9-22 months). No bone graft failure, internal fixation broken, pleural effusion, cerebrospinal fluid leakage, wound infection, fistula formation, and other complications occurred. Satisfactory intervertebral fusion was obtained in all patients at 3-8 months (mean, 5.3 months) after surgery. The ESR, CRP, VAS score, ODI score, and Kyphosis angle were significantly improved at immediate after operation and last follow-up when compared with preoperative ones (P<0.05), and the ESR, CRP, VAS score and ODI score at last follow-up were significantly better than those at immediate after operation (P<0.05). At last follow-up, the nerve function was recovered to ASIA grade E from grade C (1 case) and grade D (6 cases). CONCLUSIONS: ?Intertransverse bone graft is a reliable, safe, and effective way of bone graft applied to the single segmental thoracic spinal tuberculosis. PMID- 29786321 TI - [One-stage posterior retaining part facet joint in laminectomy and debridement combined with short segmental pedicle screw fixation for lumbosacral spinal tuberculosis]. AB - OBJECTIVE: ?To evaluate the feasibility and effectiveness of one-stage posterior retaining part facet joint in laminectomy, bone graft and debridement combined with short segmental pedicle screw fixation for lumbosacral spinal tuberculosis. METHODS: ?Between January 2010 and December 2014, 32 cases of lumbosacral spinal tuberculosis (L4-S1) were treated by one-stage posterior retaining part facet joint in laminectomy, bone graft and debridement combined with short segmental pedicle screw fixation. There were 20 males and 12 females, aged 17-62 years (mean, 43 years). The disease duration was 12-48 months (mean, 18 months). The involved segments included L5, S1 level in 19 cases and L4, 5 level in 13 cases. The effectiveness was evaluated by Oswestry disability index (ODI) and imaging parameters (lumbar-sacral angle correction and Bridwell classification and CT fusion criteria) after operation. RESULTS: ?The operation was successfully completed in all patients; the average operation time was 180 minutes, and the average intraoperative blood loss was 400 mL. All cases were followed up 12 to 67 months (mean, 15.6 months). At last follow-up, common toxic symptom of tuberculosis disappeared, and no internal fixation failure occurred. Neurological function was recovered to normal in 7 patients with neurological symptoms, and American Spinal Injury Association (ASIA) scale was improved to grade E from grade C (2 cases) and grade D (5 cases) before operation. At 1 year and last follow-up, the ODI scores were significantly improved when compared with preoperative score (P<0.05), but no significant difference was found between at 1 year and last follow-up (P>0.05). The lumbarsacral angle was significantly increased at 7 days, 1 year and last follow-up when compared with preoperative one (P<0.05), but there was no significant difference between different time points after operation (P>0.05). The bone graft fusion time was 9-24 months (mean, 12 months). At 1 year after operation and last follow-up, X-ray Bridwill bone fusion rates were 87.50% (28/32) and 93.75% (30/32) respectively, and CT fusion rates were 87.50% (28/32) and 90.63% (29/32) respectively; and there was significant difference in interbody fusion between at 1 year and last follow-up (P<0.05). Drug resistance was observed in 4 cases; Bridwill grade III and grade IV fusion was shown in 3 cases and 1 case after adjusting the anti-tuberculosis scheme after 1 year. CONCLUSIONS: ?One-stage posterior retaining part facet joint in laminectomy and debridement can effectively clear the tuberculose focus, intervertebral bone graft combined with short segment pedicle screw fixation can maintain postoperative spinal reliable stability and get satisfactory bone fusion rate, so it is an effective method for the treatment of lumbosacral tuberculosis. PMID- 29786323 TI - [Individualized surgical management of secondary rhinoplasty for cleft lip]. AB - OBJECTIVE: ?To explore the effectiveness of transplantation of engraved autologous costal cartilage for individualized surgical management in secondary rhinoplasty for cleft lip. METHODS: ?Between September 2009 and January 2014, 350 patients with secondary nasal deformity of cleft lip were treated, including 160 males and 190 females with a mean age of 18.2 years (range, 16-56 years). Nasal deformity was caused by unilateral cleft lip in 200 cases and by bilateral cleft lip in 150 cases. The interval of lip repair and nasal deformity correction was 2 50 years (mean, 12 years). About a 2-6 cm cartilage was harvested from the 6th or 7th costal cartilage, and was engraved to the shape of "ge" in Chinese. The upper part was strengthened on both sides of the alar cartilage; the lower part was fastened to columella and nasal septum cartilages. The rest of cartilages was diced into 0.1 mm*0.1 mm*0.1 mm cubes. The columella incision was designed to "Z" plasty, and was stretched to the nasion along alar edge. The engraved autologous costal cartilage was transplanted and fixed to the collapse of nostril. The cartilage cube was transplanted and filled into the collapse of nasal root to achieve the aesthetic effect of nasal augmentation. The effectiveness was evaluated according to the grade of secondary rhinoplasty for cleft lip by ZHANG Li et al. at 1, 6, and 12 months after operation. RESULTS: ?All incisions were primary healing. All patients were followed up 1-12 months (mean, 6 months). After rhinoplasty, the collapse of nostrils was lifted, and the shape and height of collapse of nostrils were symmetrical to normal side. The deflection of columella nasi was corrected. A beautiful shape of nose was achieved. The excellent and good rates were 98.6% at 1 month, 97.4% at 6 months, and 97.1% at 12 months after operation, showing no significant difference (chi2=0.545, P=0.761). CONCLUSIONS: ?The technique of transplantation of engraved autologous costal cartilage for individualized surgical management in secondary rhinoplasty for cleft lip can achieve excellent surgery effect. PMID- 29786322 TI - [Influence of isobar ttl dynamic internal fixation system on adjacent segment degeneration by mri measurement of lumbar nucleus pulposus volume]. AB - OBJECTIVE: ?To investigate the influence of ISOBAR TTL dynamic internal fixation system on degeneration of adjacent intervertebral disc by MRI measurement of lumbar nucleus pulposus volume in treating lumbar degenerative disease after operation. METHODS: ?Between March 2010 and October 2011, 34 patients with lumbar intervertebral disc herniation (23 cases of paracentral type and 11 cases of lateral type) underwent operation with ISOBAR TTL dynamic internal fixation system for fixation of single segment, and the clinical data were analyzed retrospectively. There were 20 males and 14 females, aged 39-62 years (mean, 47.5 years). The disease duration was 6-18 months (mean, 14 months). Involved segments included L4, 5 in 21 cases and L5, S1 in 13 cases. The X-ray films and MRI images were taken at 6, 12, 18, 24, 36, and 48 months after surgery. Based on X-ray films, the height of intervertebral space was measured using angle bisectrix method. The nucleus pulposus volume was measured based on the MRI scan. The postoperative change of nucleus pulposus volume and intervertebral disc height were used to evaluate the influence of ISOBAR TTL system on degeneration of adjacent intervertebral disc nucleus pulposus. RESULTS: ?Thirty patients were followed up 48 months. The height of intervertebral space showed no significant difference between at pre-and post-operation (P>0.05). The nucleus pulposus volume increased after operation, showing no significant difference at 6, 12, and 18 months when compared with preoperative value (P>0.05), but significant difference was found at 24, 36, and 48 months when compared with preoperative value (P<0.05). The height of nucleus pulposus increased after operation but the width was decreased; the values showed no significant difference at 6, 12, and 18 months when compared with preoperative ones, but showed significant difference at 24, 36, and 48 months when compared with preoperative ones (P<0.05). The diameter of nucleus pulposus at 18, 24, 36, and 48 months after operation was significantly langer than that at preoperation (P<0.05). CONCLUSIONS: ?ISOBAR TTL dynamic internal fixation system can prevent or delay the degeneration of intervertebral discs. PMID- 29786324 TI - [Short-term effectiveness of hypospadias repair with free inner prepuce tube]. AB - OBJECTIVE: ?To explore the short-term effectiveness of hypospadias repairs with free inner prepuce tube. METHODS: ?Forty-two males with hypospadias were repaired with free inner prepuce tube between May and October 2015. The age ranged from 1 year and 1 month to 28 years and 2 months with a median of 2 years and 9 months. Initial operation for hypospadias was performed in 41 cases and re-operation in 1 case of chordee after 16 months of hypospadias repair. There were 36 cases of hypospadias ( 6 cases of proximal penile type, 1 case of penile scrotal type, 26 cases of scrotal type, and 3 cases of perineal type) and 6 cases of type IV chordee according to Donnahoo classification criteria. RESULTS: ?The length of reconstructed urethra was 2.0-5.5 cm (mean, 3.6 cm). The patients were followed up 6-10 months (mean, 8 months). Urinary fistulae was noted in 10 patients, which healed spontaneously in 5 cases within 3 months after surgery, and was cured after repair in 5 cases. Urethral stenosis occurred in 4 cases (2 external orifice stricture and 2 distal urethral stricture) and urethral incision was performed. Wound infection was noted in 3 cases, 2 of them needed further surgery for a permanent fistula. Skin ischemic necrosis was found in 3 cases, 1 of them had infection and fistula, and needed further surgical repair. Diverticulum of scrotum developed in 1 case. Ten patients need re-operation, and the success rate was 76.2% (32/42). At 3 months after surgery, the HOSE score ranged from 11 to 16 (mean, 14.7). The maximum urinary flow rate was 1.9-28.4 mL/s (mean, 10.5 mL/s) in 22 cases of outpatient at 3 months after surgery. CONCLUSIONS: ?Free inner prepuce tube can survive and play a role of normal neourethra. The short-term effectiveness has shown a relatively high complication rate and suggests this procedure should be carefully applied. PMID- 29786325 TI - [Effects of over-expressing smad7 gene on keloid fibroblasts]. AB - OBJECTIVE: ?To explore if Smad7 protein can inhibit growth of keloids by observing the gene and protein expressions of Smad7, collagen type I, and collagen type III and cell proliferation after over-expression vectors of Smad7 transfecting keloid fibroblasts (KFb). METHODS: ?Fibroblasts were acquired from 10 male patient with keloids at the age of 20 to 25 years. After in vitro culture, KFb were divided into 3 groups: untransfected group (group A), pcDNA3.1 (-) transfected group (group B), and pcDNA3.1 (-) -smad7 transfected group (group C). The mRNA and protein expression levels of Smad7, collagen type I, and collagen type III were detected by real-time fluorescence quantitative PCR and Western blot at 48 hours after transfection. The cell proliferation ability was detected by MTT assay at 24 hours after transfection. RESULTS: ?The relative expression levels of mRNA and protein of Smad7 in group C were significantly higher than those in group A and group B (P<0.01). The relative expression levels of mRNA and protein of collagen type I and collagen type III in group C were significantly lower than those in group A and group B (P<0.01). The relative expression levels of mRNA of collagen type I and collagen type III in group B were significantly higher than those in group A (P<0.01); and the relative expression levels of proteins of Smad7, collagen type I, and collagen type III were significantly lower than those in group A (P<0.01). The cell proliferation ability in group C was significantly lower than that in group A and group B at each time point by MTT assay (P<0.05), but no difference was found between group A and group B (P>0.05). CONCLUSIONS: ?Gene expressions of collagen type I, and collagen type III and cell proliferation will be inhibited after KFb are transfected by over-expression vector of Smad7. PMID- 29786326 TI - [Effect of estradiol on biofilm formation of staphylococcus epidermidis after breast implant surgery]. AB - OBJECTIVE: ?To investigate the effect of the estradiol hormones on biofilm formati on and structure of Staphylococcus epidermidis after breast implant surgery. METHODS: ?The concentration of Staphylococcus epidermidis strains ATCC35984 was adjusted to 1*107 CFU/mL or 1*108 CFU/mL, and the type strains were incubated on the surface of silica gel in 125 pmol/L estradiol suspensions to prepare bacterial biofilms model in vitro. After cultured in vitro for 4, 6, 12, 24, 48, and 72 hours, bacteria growth and biofilm formation ability were assessed by means of the XTT and crystal violet staining respectively. According to the above results, the bacterial suspension concentration was selected for experiments. The experimental concentration of Staphylococcus epidermidis ATCC35984 suspension and the concentrations of 50, 125, 250, 500 pmol/L estradiol suspensions were mixed with silica gel respectively to prepare biofilm model in vitro, no estradiol suspension served as control group. The experimental concentration of Staphylococcus epidermidis ATCC12228 suspension was used to prepare the same model in the negative control. After cultured in vitro for 4, 6, 12, 24, 48, and 72 hours, the same methods were used to assess the bacteria growth dynamics and biofilm forming ability, and the scanning electron microscope (SEM) was used to observe bacterial biofilm structure cultured on the surface of silica gel; the laser scanning confocal microscope (CLSM) was used to measure bacterial biofilm thickness on the surface of silica gel after 6, 12, and 24 hours. RESULTS: ?According to the results of semi quantitative detection of crystal violet stain and XTT methods, the bacterial suspension of 1*107 CFU/mL was selected for the experiment. XTT results indicated that the growth rates of ATCC12228 strain (at 4, 6, 12, 24, and 72 hours ) and ATCC35984 strain (at 4, 6, 24, and 72 hours) in 125, 250, and 500 pmol/L estradiol were significantly faster than those in 0 and 50 pmol/L (P<0.05). The growth rate of 500 pmol/L group was significantly faster than 125 and 250 pmol/L groups at 4, 6, and 72 hours (P<0.05), and the growth rate of 250 pmol/L group was significantly faster than that of 125 pmol/L group at 72 hours (P<0.05), but there was no significant difference between 0 and 50 pmol/L groups (P>0.05). At the same time point and same estradiol concentration, the growth rates showed no significant difference between 2 strains (P>0.05). Semi quantitative detection of crystal violet staining showed no biofilm formed in ATCC12228 strain in all estradiol concentration groups at different time points. In ATCC35984 strain, the biofilm was found at 4 hours and gradually thickened with time, reached the peak at 24 hours. After cultured for 4 and 6 hours, the biofilm of 0 pmol/L groups were significantly thicker than that of 125, 250, and 500 pmol/L groups (P<0.05). At 12 hours, the 125 pmol/L group had the thickest biofilm, showing significant difference when compared with other groups (P<0.05). The CLSM showed ATCC35984 biofilm thickness of 125, 250, and 500 pmol/L was significantly less than that of 0 and 50 pmol/L groups at 6 hours (P<0.05), but difference was not significant between other groups (P>0.05). Then the thickness of the biofilm increased gradually, and the thickness of 125 pmol/L group was significantly larger than that of other concentration groups at 12 and 24 hours (P<0.05). The SEM observation showed that the biofilm of 125 pmol/L group was denser and thicker than that of the other concentration groups at each time point. CONCLUSIONS: ?High level estradiol can promote bacteria growth, biofilm formation, and biofilm maturity of Staphylococcus epidermidis. PMID- 29786327 TI - [In vivo degradation of magnesium alloys and poly (lactic-co-glycolic acid) and degradation evaluation of magnesium alloys using micro-ct]. AB - OBJECTIVE: ?To explore the degradation of AZ31 magnesium alloy and poly (lactic co-glycolic acid) (PLGA) in the femoral condyle, and then evaluate the laws of degradation of AZ31 magnesium alloy by Micro-CT images and data. METHODS: ?Forty 3-month-old male New Zealand white rabbits (weighing, 2.5 kg) were randomly divided into 4 groups, 10 rabbits each group. Forty micro-arc-oxidized AZ31 magnesium alloy pins and 40 PLGA pins were implanted into the right and left femoral condyle, respectively. Micro-CT images and data analysis were used to evaluate the degradation at 4, 8, 12, and 16 weeks after operation (n=10). Degradation was evaluated by weight difference between pre-and post-implantation. The inflammatory response was observed around the implants by HE staining. The weight loss of magnesium alloy and Micro-CT results were compared. RESULTS: ?The Micro-CT images showed that PLGA pins had gray low signal, which was similar to the soft tissue around. At 4 weeks after operation, no signs of degradation were observed, and there were little corrosion pitting on the magnesium alloy. At 8 weeks, corrosion pitting gradually expanded, the boundary between the longitudinal axis and the cross section became blurred; at 16 weeks, corrosion pitting became bigger, and the boundary was discontinuous. Micro-CT quantitative analysis showed that the volume fraction of magnesium pins decreased slowly at 4 and 8 weeks; it was significantly lower at 12 and 16 weeks than 4 and 8 weeks (P<0.05). The magnesium cylinder mineral density continuously decreased during the study period, it had a rapidly speed from 12 to 16 weeks (P<0.05). However, the magnesium CT image density showed a slight change (P>0.05). The surface-to volume ratio of the pins constantly increased, and the ratio was significantly larger at 12 and 16 weeks than 4 and 8 weeks, and at 16 weeks than 12 weeks (P<0.05). There was more and more corrosion pitting on the surface with time, which resulted in a decrease in the radius that mean trabecular thickness gradually decreased, showing significant difference between different time points after 8 weeks (P<0.05). The weight loss detection showed that the degradation of magnesium pin and PLGA gradually increased with time (P<0.05), and the degradation rate of magnesium pin was significantly lower than that of PLGA at 8 12 weeks (P<0.05), but the degradation rate of magnesium pin was higher than that of PLGA at 16 weeks. At each time point, the weight loss of magnesium alloy was similar to that by Micro-CT, but mass fraction was lower than volume fraction and had significant differences at 8, 12, and 16 weeks (P<0.05). HE staining revealed that slight inflammatory response was observed around the magnesium pins at 4 weeks, and inflammatory reaction gradually reduced with time and disappeared at 16 weeks, but no inflammatory reaction was seen around PLGA. CONCLUSIONS: ?Micro CT has the advantages of non-trauma, in vivo detection, quantitative analysis, and precise data in evaluating the degradation of AZ31 magnesium alloy. Regarding the degradation of the magnesium alloy and PLGA in vivo, the degradation rate is slow in the early stage, and then increases with time. The degradation of PLGA is faster and earlier but it is then overtaken by AZ31 magnesium alloy at 16 weeks. During the degradation, the density of the magnesium has almost no change. The biomaterials can not firmly attach to the surrounding tissues due to inadequate holding forces. PMID- 29786328 TI - [Effect of indianhedgehog gene transfection into rabbit bone marrow mesenchymal stem cells in promoting chondrogenic differentiation and inhibiting cartilage aging in rotary cell culture system]. AB - OBJECTIVE: ?To investigate the effect of overexpressing the Indianhedgehog (IHH) gene on the chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells (BMSCs) in a simulated microgravity environment. METHODS: ?The 2nd generation BMSCs from rabbit were divided into 2 groups: the rotary cell culture system (RCCS) group and conventional group. Each group was further divided into the IHH gene transfection group (RCCS 1 group and conventional 1 group), green fluorescent protein transfection group (RCCS 2 group and conventional 2 group), and blank control group (RCCS 3 group and conventional 3 group). RCCS group cells were induced to differentiate into chondrocytes under simulated microgravity environment; the conventional group cells were given routine culture and chondrogenic induction in 6 well plates. During differentiation induction, the ELISA method was used to detect IHH protein expression and alkaline phosphatase (ALP) activity, and quantitative real-time PCR to detect cartilage and cartilage hypertrophy related gene expressions, and Western blot to detect collagen type II, agreecan (ANCN) protein expression; and methylene blue staining and Annexin V cy3 immunofluorescence staining were used to observe cell slide. RESULTS: ?After transfection, obvious green fluorescence was observed in BMSCs under fluorescence microscopy in RCCS groups 1 and 2, the transfection efficiency was about 95%. The IHH protein levels of RCCS 1 group and conventional 1 group were significantly higher than those of RCCS 2, 3 groups and conventional 2, 3 groups (P<0.05); at each time point, ALP activity of conventional 1 group was significantly higher than that of conventional 2, 3 groups (P<0.05); ALP activity of RCCS 1 group was significantly higher than that of RCCS 2 and 3 groups only at 3 and 7 days (P<0.05). Conventional 1 group expressed high levels of cartilage-related genes, such as collagen type II and ANCN at the early stage of differentiation induction, and expressed high levels of cartilage hypertrophy-related genes, such as collagen type X, ALP, and Annexin V at the late stage (P<0.05). RCCS 1 group expressed high levels of cartilage-related genes and low levels of cartilage hypertrophy-related genes at all stages. The expression of collagen type II protein in conventional 1 group was significantly lower than that of conventional 2 and 3 groups at 21 days after induction (P<0.05); RCCS 1 group expressed high levels of collagen type II and ANCN proteins at all stages (P<0.05). Methylene blue staining indicated conventional 1 group was stained lighter than conventional 2 and 3 groups at 21 days after induction; while at each time point RCCS 1 group was significantly deeper than RCCS 2 and 3 groups. Annexin V-cy3 immunofluorescence staining indicated the red fluorescence of conventional 1 group was stronger than that of conventional 2 and 3 groups at each time point. The expression of red fluorescence in each RCCS subgroup was weak and there was no significant difference between the subgroups. CONCLUSIONS: ?Under the simulated microgravity environment, transfection of IHH gene into BMSCs can effectively promote the generation of cartilage and inhibit cartilage aging and osteogenesis. Therefore, this technique is suitable for cartilage tissue engineering. PMID- 29786329 TI - [Comparative study between hypoxia and hypoxia mimetic agents on osteogenesis of bone marrow mesenchymal stem cells in mouse]. AB - OBJECTIVE: ?To compare the effects on the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) between hypoxia and hypoxia mimetic agents dimethyloxalylglycine (DMOG) under normal oxygen condition. METHODS: ?BMSCs were isolated and cultured from healthy 3-4 weeks old Kunming mouse. Cell phenotype of CD29, CD44, CD90, and CD34 was assayed with flow cytometry; after osteogenic, adipogenic, and chondrogenic induction, alizarin red staining, oil red O staining, and toluidine blue staining were performed. The passage 3 BMSCs were cultured under normal oxygen in control group (group A), under 1%O2 in hypoxia group (group B), and under normal oxygen and 0.5 mmol/L DMOG in DMOG intervention group (group C). BMSCs proliferation was estimated by methyl thiazolyl tetrazolium assay at 1, 2, 3, and 4 days. Alkaline phophatase (ALP) expression was determined at 7 and 14 days after osteogenic induction. Western blot was employed for detecting hypoxia inducible factor-1alpha (HIF-1alpha) at 24 hours. Real time fluorescence quantitative PCR was employed for detecting the mRNA expression of runt-related transcription factor 2 (RUNX2) and Osterix at 3 and 7 days. Alizarin red staining was applied to assess the deposition of calcium tubercle at 21 days. RESULTS: ?The BMSCs presented CD29(+), CD44(+), CD90(+), and CD34(-); and results of the alizarin red staining, oil red O staining, and toluidine blue staining were positive after osteogenic, adipogenic, and chondrogenic induction. No significant difference in BMSCs proliferation was observed among 3 groups at 1 day (P>0.05); compared with group A, BMSCs proliferation was inhibited in group C at 2, 3, and 4 days, but no significant difference was observed (P>0.05); compared with group A, BMSCs proliferation was significantly promoted in group B (P<0.05). At each time point, compared with group A, the ALP expression, HIF-1alpha protein relative expression, and mRNA relative expressions of RUNX2 and Osterix were significantly up-regulated in groups B and C (P<0.05); compared with group B, the ALP expression, the RUNX2 and Osterix mRNA relative expression were significantly up-regulated in group C (P<0.05); compared with group C, the HIF-1alpha protein relative expression was significantly up-regulated in group B (P<0.05). The alizarin red staining showed little red staining materials in group A, some red staining materials in group B, and a large number of red staining materials in group C. CONCLUSIONS: ?Hypoxia can promote BMSCs proliferation, DMOG can not influence the BMSCs proliferation; both hypoxia and DMOG can improve osteogenic differentiation of BMSCs, and DMOG is better than hypoxia in improving the BMSCs osteogenesis. PMID- 29786330 TI - [Reseach development of vascular anatomy and preoperative design technology of anterolateral thigh flap]. AB - OBJECTIVE: ?To summarize the present status and progress of vascular anatomy and preoperative design technology of the anterolateral thigh flap. METHODS: ?The relative researches focused on vascular anatomy and preoperative design technology of the anterolateral thigh flap were extensively reviewed, analyzed, and summarized. RESULTS: ?Vascular anatomy of the anterolateral thigh flap has been reported by numerous researchers, but perforators' location, origin, course, and the variation of the quantity have been emphasized. Meanwhile, the variation of descending branch, oblique branch, and lateral circumflex femoral artery has also been widely reported. Preoperative design technology of the anterolateral thigh flap includes hand-held Doppler, Color Doppler, CT angiography (CTA), magnetic resonance angiography, digital subtraction angiography, and digital technology, among which the hand-held Doppler is most widely used, and CTA is the most ideal, but each method has its own advantages and disadvantages. CONCLUSIONS: ?There is multiple variation of vascular anatomy of the anterolateral thigh flap. Though all kinds of preoperative design technologies can offer strong support to operation of anterolateral thigh flap, a simple, quick, precise, and noninvasive technology is the direction of further research. PMID- 29786331 TI - [APPLICATION OF THREE-DIMENSIONAL PRINTING CUSTOMIZED BONE CEMENT MODELS ON REPAIR OF BONE DEFECT OF LIMBS]. AB - OBJECTIVE: To determine the feasibility of fabricating molds using a three dimensional (3D) printer for producing customized bone cement for repairing bone defect. METHODS: Between February 2015 and March 2016, 13 patients with bone defects were treated. There were 9 males and 4 females with an average age of 38.4 years (range, 20-58 years), including 7 cases of chronic osteomyelitis, 3 cases of bone tuberculosis, 2 cases of bone tumor, and 1 case of ischemic necrosis. The defect located at the humerus in 3 cases, at the femur in 4 cases, and at the tibia in 6 cases. The defect ranged from 4.5 to 8.9 cm in length (mean, 6.7 cm). Before operation, Mimics10.01 software was used to design cement prosthesis, 3-matic software to design shaping module which was printed by 3D technology. After removal of the lesion bone during operation, bone cement was filled into the shaping module to prepare bone cement prosthesis for repairing defect. RESULTS: The measurement result from Image J software showed that the match index of interface between the mirror restored digital and bone interface was 95.1%-97.4% (mean, 96.3%); the match index of interface between bone cement prosthesis and bone interface was 91.2%-94.7% (mean, 93.2%). It was one time success during separation between formed bone cement and shaping module without any shatter or fall off. All incisions healed by first intention. The cases were followed up 5-17 months (mean, 9.4 months). X-ray films and CT scans showed good position of bone cement prosthesis without any fracture; no peripheral fracture occurred. CONCLUSIONS: 3D printing customized bone cement shaping module can shorten the operation time, and customized bone cement prothesis has good match with bone interface, so it can avoid further adjustment and accord with the biomechanical rules of surgical site. PMID- 29786332 TI - [Ilizarov TECHNIQUE FOR TREATMENT OF INFECTION AFTER LIMB SALVAGE OPERATION OF PRIMARY BONE TUMOR]. AB - OBJECTIVE: To investigate the application value of the Ilizarov technique for infection after the limb salvage operation of primary bone tumor. METHODS: A retrospective analysis was made on the clinical data of 6 patients with infection treated with Ilizarov technique after limb salvage operation of primary bone tumor between July 2012 and April 2015. There were 4 males and 2 females, aged 18 40 years (mean, 28 years). Tumor types included 3 cases of osteosarcoma and 3 cases of giant cell tumor of bone. Tumor located at the left distal femur in 2 cases, at the right distal femur in 1 case, at the left proximal tibia in 1 case, and at the right proximal tibia in 2 cases. Six cases had recurring infection after debridement. The patients underwent operation 2 to 5 times (mean, 3.5 times). The time from tumor resection to visiting was 8-20 months (mean, 14.3 months). During operation, the internal implant was removed; infection and necrotic tissue was removed thoroughly; and the Ilizarov external fixator was installed. After operation, gentamycin normal saline was used for 2 to 3 weeks, and the sensitive antibiotic intravenous infusion was performed at the same time. After 1 week, the osteotomy lengthening was used. RESULTS: All 6 patients were followed up for 6 to 18 months (mean, 12.2 months). Pin tract infection occurred in 1 case after operation; primary healing of incision was obtained in the other patients, and no related complications occurred. The external fixation time ranged from 6 to 16 months (mean, 11.5 months). The healing indexes ranged from 34 to 62 days/cm (mean, 52.0 days/cm). After removal of the external fixator, the knee range of motion ranged from 0 to 5 degrees (mean, 3 degrees ) in extension, and from 120 to 130 degrees (mean, 125 degrees ) in flexion. The American musculo-skeletal tumor society system (MSTS) function scoring was excellent in 3 patients, good in 2 patients, and fair in 1 patient, with an excellent and good rate of 83.3%. During follow-up period, there was no recurrence of infection; and no recurrence or metastasis was found in 3 patients with osteosarcoma. CONCLUSIONS: Infection can be cured by Ilizarov technique after limb salvage operation of bone tumor. PMID- 29786333 TI - [EFFECTIVENESS OF Ilizarov TECHNOLOGY FOR INFECTED FOREARM NONUNION]. AB - OBJECTIVE: To explore the effectiveness and method of Ilizarov technology for the treatment of infected forearm nonunion. METHODS: Between January 2004 and March 2014, 19 patients with infected forearm nonunion were treated, including 12 males and 7 females with a mean age of 37.4 years (range, 18-62 years). The injury causes included traffic accident in 11 patients, falling from height in 4 patients, and machine twist injury in 4 patients. The patients had received surgical treatment for 1-5 times (mean, 2.7 times). Bone defects located at the radius in 10 cases, at the ulna in 7 cases, and at the radius and ulna in 2 cases. The mean time of chronic infection was 8.3 months (range, 4-16 months). The mean length of the bone defects after debridement was 3.54 cm (range, 2.2-7.5 cm). Under the guidance of C-arm fluoroscope, the Orthofix unilateral external fixator was used to fix. Distraction was performed at 7-10 days after operation, and X-ray film was taken regularly to detect the osteogenesis. RESULTS: The mean external fixation time was 6.5 months (range, 3-12 months), and the mean external fixation index was 1.72 months/cm (range, 1.14-2.15 months/cm). All patients were followed up for 35.4 months on average (range, 24-55 months). The bone union time was 3-11 months (mean, 6 months); and no recurrence of infection was observed. At last follow-up, the mean wrist range of motion (ROM) were 52.78 degrees (range, 42-55 degrees ) in flexion and 46.53 degrees (range, 40-60 degrees ) in extension; the mean elbow ROM were 139.23 degrees (range, 130-150 degrees ) in flexion and 3.57 degrees (range, 0-20 degrees ) in extension; and the mean forearm ROM were 76.68 degrees (range, 68-90 degrees ) in pronation and 81.75 degrees (range, 72-90 degrees ) in supination. CONCLUSIONS: Ilizarov technology for infected forearm nonunion can acquire satisfactory clinical results. Radical debridement is the key to control bone infection. PMID- 29786334 TI - [EFFECTIVENESS OF POSTEROMEDIAL DOUBLE PLATES IN TREATMENT OF COMPLEX OLECRANAL FRACTURE]. AB - OBJECTIVE: To evaluate the effectiveness of posteromedial double plates in the treatment of complex olecranal fracture. METHODS: Between September 2011 and July 2015, 13 patients with complex olecranal fractures were treated with posterior olecranon locking compression plate and medial mini-plate. There were 8 males and 5 females with an average age of 41.6 years (range, 22-68 years). Injury was caused by traffic accident in 4 cases, falling from height in 6 cases, and crush by object in 3 cases. According to the Mayo classification, fracture was rated as Mayo type IIB in 5 cases and as Mayo type IIIB in 8 cases. Of 13 cases, 7 had Regan-Morrey type III coronoid fractures, including 5 anterior dislocations of the elbow joint and 2 posterior dislocations. The time between injury and admission ranged from 1.5 to 10.0 hours (mean, 5.7 hours). At last follow-up, the elbow function was assessed according to the Broberg-Morrey evaluation criteria. X-ray films was performed to observe fracture healing. RESULTS: All incisions healed at first stage and no neural complications occurred. The patients were followed up 9-38 months (mean, 22.1 months). All patients achieved bone union at 3.0-5.5 months (mean, 3.7 months) according to X-ray results. Subluxation of radial head and mild heterotopic ossification occurred in 1 patient respectively, who had no uncomfortable symptoms of movement disorder, elbow instability and pain, and no special management was performed. At last follow-up, the flexion and extension range of motion (ROM) of the elbow was 95-130 degrees (mean, 116.4 degrees ); the rotation ROM of the forearm was 150-175 degrees (mean, 170.8 degrees ); and the elbow function was excellent in 4 cases, good in 7 cases, and fair in 2 cases, and the excellent and good rate was 84.6%. No internal fixation failure, elbow stiffness, or traumatic arthritis occurred. CONCLUSIONS: For complex olecranal fractures, an early and stable anatomic reconstruction of trochlear notch in the olecranon with posterior olecranon locking compression plate and medial mini-plate can obtain good effectiveness in joint functions. PMID- 29786335 TI - [COMPARISON OF HISTOACRYL TOPICAL SKIN ADHESIVE AND TRADITIONAL METHOD FOR WOUND CLOSURE IN TOTAL HIP ARTHROPLASTY]. AB - OBJECTIVE: To compare the effectiveness between histoacryl topical skin adhesive and traditional method for wound closure in total hip arthroplasty (THA). METHODS: A total of 159 patients undergoing THA were divided into 2 groups between January and October in 2015. Subcuticular suture and histoacryl topical skin adhesive (cyanoacrylate adhesive) were used in 80 patients (100 hips) (test group), and traditional method (skin staples and wound drainage) was used in 79 patients (100 hips) (control group) for wound closure. There was no significant difference (P>0.05) in gender, age, body mass index, and etiology between 2 groups. The operation time, length of stay, incision pain visual analogue scale (VAS) score and healing of incision, and incision satisfaction evaluation, and classification were compared between 2 groups. RESULTS: All patients were followed up 3-6 months (mean. 4.7 months). There was no significant difference in operation time between 2 groups (Z=-0.527, P=0.598); but the length of stay of test group was less than that of control group (Z=-2.004, P=0.045). Incision exudation and dehiscence occurred in 1 case (1 hip) and 1 case (1 hip) of test group respectively; incision swollen, persistent wound exudation, exudation, and sutured drainage tube occurred in 2 cases (2 hips), 2 cases (2 hips), 4 cases (4 hips), and 1 case (1 hip) of control group. No statistically significant difference was found in VAS score between 2 groups at 15 days after operation (Z= 0.125, P=0.901), but wound healing score of test group was significantly higher than that of control group (Z=-2.943, P=0.003). Wound healing was class A in 98 hips and class B in 2 hips in test group, and was class A in 92 hips and class B in 8 hips in control group, and difference was statistically significant (chi2=3.789, P=0.048). The incision satisfaction of test group was significantly higher than that of control group (Z=-2.626, P=0.009). CONCLUSIONS: Compared with traditional method, histoacryl topical skin adhesive has decreased wound complication rate, and it is an easy and safe method with high satisfaction. PMID- 29786336 TI - [CURATIVE EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS BY INTRA ARTICULAR INJECTION FOR DEGENERATIVE KNEE OSTEOARTHRITIS]. AB - OBJECTIVE: To investigate the safety and efficacy of human umbilical cord mesenchymal stem cells (MSCs) by intra-articular injection for degenerative knee osteoarthritis. METHODS: Between January 2015 and January 2016, 36 patients with moderate or severe degenerative knee osteoarthritis were randomly devided into 2 groups (n=18). Intra-articular injection of 2.5-3.0 mL human umbilical cord MSCs suspension containing (2-3)*107 cells was performed once a month for 2 times as a course of treatment in the cell treatment group; sodium hyaluronate by intra articular injection was used once a week for 5 times as a course of treatment in the control group. There was no significant difference in gender, age, body mass index, side, stage of osteoarthritis, course of disease, and preoperative Lysholm score of the knee joint, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and SF-36 scale score between 2 groups (P>0.05). The clinical efficacy was evaluated by SF-36 scale score, Lysholm score, and WOMAC score. RESULTS: All patients of 2 groups received a course of treatment. The patients were followed up for 6 months. After injection, the incidences of pain and swelling in the cell treatment group were significantly higher than those in the control group (chi2=16.200, P=0.000; chi2=11.688, P=0.000), but no significant difference was found in the incidence of effusion (chi2=2.118, P=0.146). In the cell treatment group, Lysholm score at 1-6 months after treatment, WOMAC score and SF-36 scale score at 2-6 months after treatment were significantly better when compared with scores before treatment (P<0.05), and no recurrence of knee pain was observed during follow-up. In the control group, there was no significant difference in Lysholm score and SF-36 scale score between pre- and post-treatment (P>0.05); there were significant differences in WOMAC score between pre-treatment and at 1, 2, 3 months after treatment (P<0.05); at 3 months after treatment, 11 patients had joint pain symptoms again. No significant difference was found in the knee joint function score and SF-36 scale score at 1 and 2 months after treatment between 2 groups (P>0.05), but the scores of the cell treatment group were significantly better than those of the control group at 3 and 6 months (P<0.05). CONCLUSIONS: It can significantly improve the joint function and quality of life to use intra-articular injection of human umbilical cord MSCs for treating degenerative knee osteoarthritis. It takes effect after 1 month and the treatment effect can be sustained for 6 months. PMID- 29786338 TI - [IMPROVED DOUBLE OPERATIVE APPROACHES FOR TREATMENT OF Pilon FRACTURES ACCOMPANIED WITH FIBULA FRACTURES]. AB - OBJECTIVE: To investigate the clinical effect of surgical treatment of Pilon fractures accompanied with fibula fractures with the improved double operative approaches. METHODS: Between January 2012 and June 2015, 19 patients with closed Pilon fractures accompanied with fibula fractures (Ruedi-Allgower type III) underwent open reduction and internal fixation with improved anterior-median incision and posterior-lateral incision. There were 13 males and 6 females, aged 35 years on average (range, 23-68 years). Injury was caused by traffic accident in 11 cases, falling from height in 7 cases, and crash injury of heavy object in 1 case. According to AO/OTA classification, there were 4 cases of type C2, and 15 cases of type C3. According to Tscherne-Gotzen classification of soft tissue defect, 6 cases were rated as grade 1 and 13 cases as grade 2. The interval of injury and operation was 6-18 days (mean, 10.3 days). After operation, reduction of Pilon fracture was evaluated by the Burwell-Charnley radiological evaluation criteria, and the ankle joint function was evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: The operation time was 1.8-4.6 hours (mean, 2.4 hours); the intraoperative blood loss was 200-500 mL (mean, 310 mL). All the 19 patients were followed up for 13.7 months on average (range, 12-18 months). The fracture healing time was 3.6 months on average (range, 2.5-8.0 months). Postoperative complications included anterior-median incision necrosis in 2 cases, traumatic arthritis in 2 cases, and ankle instability in 1 case. According to Burwell-Charnley radiological evaluation criteria, anatomical reduction was obtained in 15 cases and satisfactory reduction in 4 cases. According to AOFAS score, the excellent and good rate was 84.2% (excellent in 11 cases, good in 5 cases, and fair in 3 cases). CONCLUSIONS: The improved anterior-median incision combined with posterior-lateral incision is a safe and effective method to treat complex Pilon fractures accompanied with fibula fractures, which has the advantages of simple operation, adequate exposure and minimal invasion. PMID- 29786337 TI - [ASSOCIATION OF ANTERIOR CRUCIATE LIGAMENT DEGENERATION WITH MEDIAL MENISCUS TEAR AND INTERCONDYLAR NOTCH IMPINGEMENT]. AB - OBJECTIVE: To explore the association of anterior cruciate ligament (ACL) degeneration with intercondylar notch impingement and the medial meniscus tear in knee osteoarthritis (KOA). METHODS: Between July 2014 and February 2016, 55 KOA patients (55 knees) with ACL degeneration (degeneration group) and 55 KOA patients (55 knees) without ACL degeneration (control group) were included in the study. No significant difference was found in gender, age, body mass index, and side between 2 groups (P>0.05). The notch width index was measured on preoperative MRI to evaluate whether the intercondylar notch was narrow. The location of the medial and lateral meniscus tear and osteophyte of the ACL tibial insertion were observed under arthroscopy, and the incidences of the meniscus tear and osteophyte were calculated. RESULTS: There was no significant difference in anterior horn and body tear of the medial meniscus and in anterior horn, body, posterior horn, and root tear of the lateral meniscus (P>0.05). Significant difference was found in the posterior horn and root tear of the medial meniscus, osteophyte of the ACL tibial insertion, narrow intercondylar notch, and the notch width index between 2 groups (P<0.05). The incidence of root tear of the medial meniscus was 53.8% (7/13) in 13 knees with osteophyte of the ACL tibial insertion and was 16.5% (16/97) in 97 knees without osteophyte, showing significant difference (chi2=9.671, P=0.002). CONCLUSIONS: There is a strong association of ACL degeneration with posterior horn and root tear of the medial meniscus and intercondylar notch impingement in KOA. And the high incidence of root tear of the medial meniscus in knee is correlated with osteophyte of the ACL tibial insertion. PMID- 29786339 TI - [APPLICATION OF POSTEROLATERAL APPROACH FOR TREATMENT OF BIMALLEOLAR AND TRIMALLEOLAR FRACTURES]. AB - OBJECTIVE: To evaluate the advantage of single posterolateral approach for exposing the fragments of lateral malleolus and posterior malleolus in treating bimalleolar and trimalleolar fractures. METHODS: Between January 2013 and June 2015, 47 patients with ankle fractures were treated. Of 47 cases, 16 were male and 31 were female with an average age of 47.7 years (range, 25-65 years); the locations were the left side in 21 cases and the right side in 26 cases. According to types system of Lauge-Hansen, 11 cases were rated as pronation external rotation and 36 cases as supination-external rotation. There were 9 cases of bimalleolar fractures and 38 cases trimalleolar fractures. CT examination showed that posterior malleolus fracture involved more than 35% of the joint surface in 11 cases, and 9 cases had comminuted posterior malleolus fracture. Of 47 cases, 44 had fresh fractures with a mean disease course of 4 days (range, 8 hours to 7 days), and 3 had old fracture with the disease course of 43, 58, and 62 days respectively. Posterior malleolus fractures were fixed with T-type plates in 12 cases, one-third tubular plates in 10 cases, and cannulated screws in 25 cases. RESULTS: The operation time was 60-100 minutes (mean, 80 minutes); the bleeding volume was 50-100 mL (mean, 72 mL). Primary healing of incision was obtained in all patients, and no postoperative complications of infection, cutaneous necrosis, deep venous thrombosis, and sural nerve injury occurred. The CT examinations after operation showed anatomical reduction of fractures. All patients were followed up from 12 to 20 months (mean, 16 months). No fixation failure or reduction loss was found at last follow-up. All patients could walk normally. The active dorsiflexion of the affected ankles was within 5 degrees less than normal side in 43 cases (91.5%) and 5-10 degrees less than normal side in 4 cases (8.5%). The passive dorsiflexion of the affected ankles was within 5 degrees less than normal side in 44 cases (93.6%) and 5-10 degrees less than normal side in 3 cases (6.4%). According to the Olerud Molander scoring system, the results were excellent in 40 cases, good in 5 cases, and fair in 2 cases; and the excellent and good rate was 95.7% at last follow-up. CONCLUSIONS: The single posterolateral approach could simultaneously expose the fragments of lateral malleolus and posterior malleolus, with less complication of the incision, short operation time, and clear exposure of posterior malleolus. The surgery could be performed under direct vision. It especially is suitable for bimalleolar and trimalleolar fractures with lateral malleolus and posterior malleolus. PMID- 29786340 TI - [EXPERIMENTAL STUDY ON EFFECT OF NICOTINE INTAKE ON IMPACT OF BONE MICROSTRUCTURE AND OXIDATIVE STRESS IN RATS]. AB - OBJECTIVE: To evaluate the influence of nicotine intake on bone microstructure, bone biomechanics, and oxidative stress state in rats. METHODS: Thirty-six 6-week old male Sprague Dawley rats (weight, 160-180 g) were randomly divided into control group, low dose group, and high dose group, 12 rats each group. The rats in high dose group and low dose group were given respectively 6.0 mg/kg and 0.4 mg/kg nicotine gavage intervention for 12 months; no intervention was made in the control group. The survival of rats was observed during experiment, and the weight of rats was measured every month. At 12 months after modeling, the L1 vertebral body was harvested to measure the bone mineral density (BMD), bone volume fraction (BVF), trabecular thickness (TT), trabecular number (TN), and trabecular spacing (TS) by Micro-CT three-dimensional reconstruction; the left femur was harvested for biomechanical tests of maximal load, stiffness, and the maximal fracture energy; and arterial blood was extracted to measure the malonyldialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and cotinine. RESULTS: During the experiment, two rats and one rat were added in the high dose group and the low dose group because of death, and no death in the control group. The body weight of the rats in the high and low dose groups gradually decreased with time when compared with one in the control group, and significant difference was found between two dose groups and the control group at 8-12 months (P<0.05); the body weight of the high dose group was significantly lower than that of the low dose group at 11 and 12 months (P<0.05). At 12 months after modeling, BMD, BVF, TT, and TN were significantly lower in the high dose group than the control group and the low dose group, but TS was significantly increased (P<0.05). Difference in BVF, TN, and TS was significant between the low dose group and the control group (P<0.05). The maximal load, stiffness, and maximal fracture energy of femoral shaft were significantly lower in the high dose group than the control group and the low dose group, and in the low dose group than the control group (P<0.05). Compared with the control group, the levels of cotinine and MDA were significantly increased, and the levels of CAT and SOD were significantly decreased in the high and low dose groups (P<0.05), and there were significant differences between the high and low dose groups (P<0.05). CONCLUSIONS: Nicotine intake can cause micro-structural changes of the bone, decreased bone mechanical properties, and imbalance of oxidation antioxidant levels in rats. High-dose nicotine intake may be one of the causes of osteoporosis. PMID- 29786341 TI - [APPLICATION OF PEDICLED LATISSIMUS DORSI KISS FLAP TO REPAIR CHEST WALL SKIN DEFECTS AFTER TUMOR RESECTION]. AB - OBJECTIVE: To investigate the clinical value of pedicled latissimus dorsi Kiss flap in repairing chest wall large skin defect after tumor operation. METHODS: A retrospective analysis was made on the clinical data from 15 cases of chest wall tumors treated between December 2010 and December 2015. There were 2 males and 13 females with an average age of 51.8 years (range, 43-60 years); there were 11 cases of locally advanced breast cancer, 3 cases of fibrosarcoma in chest wall, and 1 case of chest wall radiation ulcer with a median disease duration of 24.1 months (range, 6 months to 8 years). The area of skin defects was 17 cm*12 cm to 20 cm*18 cm after primary tumor resection; the pedicled latissimus dorsi Kiss flap was designed to repair wounds. The flap was a two-lobed flap at a certain angle on the surface of latissimus dorsi based on the thoracodorsal artery, with a size of 17 cm*6 cm to 20 cm*9 cm for each lobe. The donor site was sutured directly. RESULTS: Fourteen flaps survived with primary healing of wound; delayed healing was observed in 1 flap because of distal necrosis; and healing by first intention was obtained at the donor sites. The follow-up time was from 6 months to 3 years (mean, 21.6 months). The flap had good appearance with no bloated pedicle. The shoulder joint activities were normal. No local recurrence occurred, but distant metastasis in 2 cases. No obvious scar was found at donor sites. CONCLUSIONS: The application of pedicled latissimus dorsi Kiss flap to repair chest wall skin defects after tumor resection has important clinical value, because of the advatages of simple operation, minor donor site damage and rapid postoperative recovery, especially for late stage cancer patients. PMID- 29786342 TI - [DESIGN AND CLINICAL APPLICATIONS OF DISTALLY BASED ANTEROMEDIAL THIGH FLAPS PEDICLED WITH PERFORATING VESSELS FROM RECTUS FEMORIS BRANCH]. AB - OBJECTIVE: To explore the feasibility and technical essentials of soft tissue defect reconstruction of the lower extremity using the distally based anteromedial thigh flap (dAMT) pedicled with perforating vessels from rectus femoris branch. METHODS: Between July 2008 and December 2015, 6 patients underwent defect reconstruction of the lower extremity using the dAMT flap pedicled with perforating vessels from rectus femoris branch. There were 4 males and 2 females with an average age of 34 years (range, 4-55 years). The etiologies included liposarcoma in 1 case, malignant fibrous histocytoma in 1 case, post burn scar contracture around the ankle in 1 case, and post-burn scar contracture around the knee in 3 cases. The disease duration ranged from 3 to 28 months (mean, 13 months). After resection of lesion tissues, the defect size ranged from 13 cm*7 cm to 24 cm*12 cm. The flap size ranged from 15 cm*8 cm to 24 cm*12 cm. The length of the pedicle ranged from 10 to 25 cm (mean, 19.8 cm). The distance from the flap pivot point to the superolateral border of the patella ranged from 8 to 13 cm (mean, 11.3 cm). The donor sites were directly sutured. RESULTS: All flaps survived postoperatively without any complications. All wounds at the donor and the recipient sites healed primarily. The patients were followed up from 5 to 36 months (mean, 17.8 months). The color, texture, and thickness of the flaps were similar to those of the surrounding skin. No tumor recurrence was observed. The range of motion of flexion and extension of the joint were greatly improved in the patients with scar contracture. CONCLUSIONS: If the rectus femoris branch gives off cutaneous branch to the anteromedial thigh region and arises from the descending branch of the lateral circumflex femoral artery, a dAMT flap could be raised to reconstruct soft tissue defects of the lower extremity. PMID- 29786343 TI - [CLINICAL APPLICATION OF LIQUID WOUND DRESSING IN TREATMENT OF CHRONIC ULCER WOUNDS]. AB - OBJECTIVE: To evaluate the effectiveness of liquid wound dressing in the treatment of chronic ulcer wounds. METHODS: Between January 2014 and October 2015, 84 patients with chronic ulcer wounds were included and divided into 2 groups randomly. The chronic ulcer wounds were covered with liquid wound dressing in the treatment group (n=44) and were managed with iodophor in the control group (n=40). There was no significant difference in age, gender, causes, location, wound area, and disease duration between 2 groups (P>0.05). The frequency of dress changing, effective rate of treatment, wound healing time, wound healing rate at 5, 10, and 20 days, positive rate of bacteria culture at 1, 5, and 10 days, and the rate of side effect were recorded and compared between 2 groups. Vancouver scar scale was used to evaluate scar formation. RESULTS: The effective rate of the treatment group (100%) was significantly higher than that of the control group (85%) (P=0.009). The frequency of dress changing in the treatment group[(11.36+/-3.40) times] was significantly lower than that in the control group[(16.94+/-4.51) times] (t=-6.231, P=0.000). The wound healing rates at 5, 10, and 20 days were significantly increased (P<0.05) and the wound healing time was significantly decreased (t=-6.627, P=0.000) in the treatment group when compared with the control group. The positive rates of bacteria culture at 5 and 10 days in the treatment group were significantly lower than those in the control group (chi2=12.313, P=0.000; P=0.005), but no significant difference was found at 1 day (chi2=0.066, P=0.797). Side effect was observed in 4 cases of the control group. Vancouver scar scale score was 8.59+/-1.32 in the treatment group and was 9.85+/-1.65 in the control group, showing significant difference (t=-3.752, P=0.000). CONCLUSIONS: The application of the liquid wound dressing in the treatment of chronic ulcer wound can improve the wound healing rate, shorten the healing time and decrease the frequency of dress change, which could promote the wound healing process. PMID- 29786344 TI - [EXPERIMENTAL STUDY ON TISSUE ENGINEERED BONES CONSTRUCTED BY HUMAN BONE MORPHOGENETIC PROTEIN 2 GENE-MODIFIED HUMAN BONE MARROW MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To investigate the bone regeneration potential of cell-tissue engineered bone constructed by human bone marrow mesenchymal stem cells (hBMSCs) expressing the transduced human bone morphogenetic protein 2 (hBMP-2) gene stably. METHODS: The full-length hBMP-2 gene was cloned from human muscle tissues by RT-PCR and connected into a vector to consturct a eukaryotic expression system. And then the gene expression system was transduced to hBMSCs with lipidosome. hBMSCs were transfected by hBMP-2 gene (experimental group) and by empty plasmid (negative control group), untransfected hBMP-2 served as blank control group. RT-PCR, dot-ELISA, immunohistochemical analysis and ALP activity were performed to compare and evaluate the situation of hBMP-2 expression and secretion after transfection. hBMSCs transfected by hBMP-2 gene were seeded on hydroxyapatite (HA) and incubated for 4 days to construct the hBMP-2 gene modified tissue engineered bone, and then the tissue engineered bone was observed by the inverted phase contrast microscope and scanning electron microscope. Then the hBMP-2 gene modified tissue engineered bone (group A, n=3), empty plasmid transfected hBMSCs seeded on HA (group B, n=3), hBMSCs suspension transfected by hBMP-2 gene (group C, n=3), and hBMP-2 plasmids and lipidosome (group D, n=3) were implanted into bilateral back muscles of nude mice. The osteogenic activity was detected by HE staining and alcian blue staining after 4 weeks. RESULTS: At 48 hours and 3 weeks after transfection, RT-PCR and dot-ELISA results indicated that the transfected hBMSCs could express and secrete active and exogenous hBMP-2 stably. The immunohistochemical staining was positive, and the ALP activity in the transfected hBMSCs was significantly higher than that in two control groups (P<0.05). The transfected hBMSCs had a good attaching and growing on the three demension suface of HA under inverted phase contrast microscope and scanning electron microscope. In vivo study indicated that a lot of new bone formation was obviously found at 4 out of 6 sides of back muscles in group A. Some new bone formation at both sides of back muscles was observed in 1 of 3 mice in group B. No new bone formation was found in group C. A few new bone formation was observed at one side of back muscles in group D. CONCLUSIONS: The tissue engineered bone constructed by hBMP-2 gene modified hBMSCs and HA is able to express and secrete active hBMP2 stably and can promote new bone formation effectively in muscles of nude mice. PMID- 29786345 TI - [EXPERIMENTAL STUDY ON OSTEOGENIC ACTIVITY OF RABBIT BONE MARROW MESENCHYMAL STEM CELLS INDUCED BY KLD-12 POLYPEPTIDE/RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2 GEL]. AB - OBJECTIVE: To investigate the effect of KLD-12 polypeptide complexed with recombinant human bone morphogenetic protein 2 (rhBMP-2) on osteogenic activity of rabbit bone marrow mesechymal stem cells (BMSCs). METHODS: Bone marrow was harvested from 3-month-old New Zealand white rabbit, and density gradient method was used to isolate and culture BMSCs. The third generation BMSCs were used for three-dimensional culture of KLD-12 polypetide/rhBMP-2 in vitro (experimental group) and KLD-12 polypeptide (control group). The morphology of the cells in the gel was observed by inverted phase contrast microscope at 7 days; alkaline phosphatase (ALP) and osteocalcin protein content were dectected at 3, 7, 10, 14, and 21 days; collagen type I immunofluorescence staining was done and real-time fluorescent quantitative PCR was performed to detect the relative expression of collagen type I and osteocalcin gene at 14 days. RESULTS: Under the inverted phase contrast microscope, the BMSCs in the gel of the experimental group and the control group showed circular growth, and the distribution was uniform at 7 days. There was no significant difference in the expressions of ALP and osteocalcin protein content between 2 groups at 3 and 7 days (P>0.05); the above indexes in experimental group were significantly higher than those in the control group at 10-21 days (P<0.05). Laser scanning confocal microscope observation showed that immunofluorescence staining for collagen type I was positive in the experimental group, and the expression was higher than that in the control group at 14 days. Real-time fluorescence quantitative PCR detection showed that the collagen type I and osteocalcin gene expressions were significantly higher than those in the control group (t=15.902, P=0.000; t=12.998, P=0.000). CONCLUSIONS: BMSCs can normally grow and proliferate in the KLD-12 polypeptide, and KLD-12 polypeptide/rhBMP-2 has good biological activity to induce BMSCs differentiation into osteoblasts. PMID- 29786346 TI - [EFFECT OF CHANGE OF TISSUE INTERFACE STIFFNESS ON OSTEOGENIC DIFFERENTIATION OF RAT BONE MARROW MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To investigate the effect of tissue interface stiffness change on the spreading, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), and to find the suitable stiffness range for stem cell differentiation. METHODS: Bone marrow of male Sprague Dawley rats (4 weeks old) were selected to isolate and culture BMSCs by whole bone marrow cell adherent method. The third generation BMSCs (1*105 cells/mL) were inoculated into the ordinary culture dishes covered with polyacrylamide hydrophilic gel (PA) which elastic modulus was 1, 4, 10, 40, and 80 kPa (cells seeded on PA), and ordinary culture dish (75 MPa extreme high elastic modulus) as control. Spreading of cells in different stiffness of PA was observed under light microscope. The elastic modulus values of 4, 10, and 40 kPa PA were selected as groups A, B, and C respectively; the ordinary culture dish (75 MPa extreme high elastic modulus) was used as control group (group D). Cell counts was used to detect the growth conditions of BMSCs, alkaline phosphatase (ALP) kit to detect the concentration of ALP, alizarin red staining technique to detect calcium deposition status, and real-time quatitative PCR technique to detect the expressions of bone gla protein (BGP), Runx2, and collagen type I mRNA. RESULTS: With increased PA stiffness, BMSCs spreading area gradually increased, especially in 10 kPa and 40 kPa. At 1 and 2 days after culture, the growth rate showed no significant difference between groups (P>0.05); at 3-5 days, the growth rate of groups B and C was significantly faster than that of groups A and D (P<0.05), but difference was not statistically significant between groups A and D (P<0.05); at 5 days, the proliferation of group C was significantly higher than that of group B (P<0.05). ALP concentrations were (53.69+/-0.89), (97.30+/-1.57), (126.60+/-14.54), and (12.93+/-0.58) U/gprot in groups A, B, C, and D respectively; groups A, B, and C were significantly higher than group D, and group C was significantly higher than groups A and B (P<0.05). Alizarin red staining showed that the percentages of calcium nodules was 20.07%+/-4.24% in group C; group C was significantly higher than groups A, B, and D (P<0.05). The expression levels of BGP and collagen type I mRNA were significantly higher in groups A, B, and C than group D, and in group C than groups A and B (P<0.05). The expression level of Runx2 mRNA was significantly higher in groups B and C than group D, and in group C than group B (P<0.05), but no significant difference was found between groups A and D (P>0.05). CONCLUSIONS: PA elastic modulus of 10-40 kPa can promote the proliferation and osteogenic differentiation of BMSCs, and the higher the stiffness, the stronger the promoting effect. PMID- 29786347 TI - [THREE-DIMENSIONAL CULTURED ADIPOSE-DERIVED STEM CELLS BASED ON MICROBIAL TRANSGLUTAMINASE ENZYME CROSSLINKED GELATIN HYDROGEL]. AB - OBJECTIVE: To study the growth of adipose-derived stem cells (ADSCs) planted in three-dimensional (3D) materials, a 3D cultured ADSCs system based on microbial transglutaminase (mTG) enzyme crosslinked gelatin hydrogel was constructed. METHODS: ADSCs were isolated from the subcutaneous adipose tissue of a Sprague Dawley rat by collagenase digestion and centrifugation, and were cultured for passage. The mTG enzyme crosslinked gelatin hydrogel was firstly synthesized by mixing gelatin and mTG, and then the ADSCs were encapsulated in situ (2D environment) and cultured in the 3D materials (3D environment). The morphology and adhesion of cells were observed by inverted phase contrast microscope. In addition, HE staining and Masson staining were carried out to observe the distribution of cells in the material. Living and death situation of ADSCs in the materials was observed by fluorescence microscope and laser scanning confocal microscopy. Scanning electron microscopy was used to observe the adhesion of ADSCs on hydrogel surface. Alamar-Blue method was used to detect the proliferation of ADSCs in the hydrogel. Moreover, the results were compared between the cells cultured in 2D environment and those in 3D environment. RESULTS: The result of 2D culture showed that ADSCs grew well on the hydrogel surface with normal functioning and had good adhesion. The results of 3D culture showed that ADSCs grew well in 3D cultured mTG enzyme crosslinked gelatin hydrogel, and presented 3D shape. Cells obviously extended in all directions. The number of apoptotic cells was very small. The cells of 3D culture at each time point was significantly less than that of the conventional culture cells, difference was statistically significant (P<0.05). But after 8 days culture, the proliferation of the cells cultured in the mTG enzyme crosslinked gelatin hydrogel increased more quickly. CONCLUSIONS: ADSCs can grow well with good adhesion and show high viability in 3D culture system constructed by mTG enzyme crosslinked gelatin hydrogel. PMID- 29786348 TI - [REGULATORY EFFECT OF OLFACTORY ENSHEATHING CELLS ON INFLAMMATORY CYTOKINES IN REPAIR OF RAT SCIATIC NERVE DEFECT]. AB - OBJECTIVE: To investigate the expression regulation of inflammation cytokines interleukin 4 (IL-4), IL-6, IL-13, and tumor necrosis factor alpha (TNF-alpha) in rats with sciatic nerve defect following olfactory ensheathing cell (OEC) transplantation. METHODS: The primary OEC for cell culture and identification was dissociated from the olfactory bulb of the green fluorescent protein-Sprague Dawley (GFP-SD) rat. One hundred SD rats were randomly divided into 2 groups, and the right sciatic nerve defect (10 mm in length) model was made, then repaired with poly (lactic acid-co-glycolic acid) (PLGA). The mixture of equivalent cultured GFP-OEC and extracellular matrix (ECM) was injected into both ends of PLGA nerve conduit in the experimental group (n=55), and the mixture of DMEM and ECM in the control group (n=45). The general situation of rats was observed after operation. At 6 hours, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 6 weeks, the inflammatory cytokines were detected by Western blot. At 2, 4, and 6 weeks, the survival of GFP-OEC was observed in the experimental group. At 9 weeks, HE staining was used to observe the morphology of nerve tissue, and the sensory and motor function and the electrophysiological index were detected. RESULTS: The cultured primary cells were GFP-OECs by immunofluorescence staining. Compared with the control group, the experimental group showed significantly increased expression level of IL-4 at 2-6 weeks (P<0.05), significantly decreased expression level of IL-6 and TNF-alpha at 3 days and 1 week (P<0.05) and significantly increased expression level of IL-13 at 1 day and 3-6 weeks (P<0.05) by Western blot detection. At 2, 4, and 6 weeks, the surviving GFP-OEC of regenerative nerve end was observed in the experimental group under the fluorescence microscope. At 9 weeks, regenerative nerve tissue was loose, and cell morphology was irregular in the experimental group, while the regenerative nerve tissue had vesicular voids and the cell number decreased significantly in the control group. At 9 weeks, the functional recovery of sciatic nerve in the experimental group was better than that of the control group, showing significant difference in the lateral foot retraction time, sciatic nerve function index, muscle action potential latency, and the amplitude of compound muscle action potential (P<0.05). CONCLUSIONS: OEC can promote the anti-inflammation cytokines expression of IL-4 and IL-13 and inhibit the pro-inflammatory cytokines expression of IL-6 and TNF-alpha, which can improve the local inflammatory microenvironment of sciatic nerve and effectively promote the structure and function recovery of sciatic nerve. PMID- 29786349 TI - [RESEARCH PROGRESS OF Hedgehog SIGNALING PATHWAY IN REGULATING BONE FORMATION AND OSTEOGENIC DIFFERENTIATION OF BONE MESENCHYMAL STEM CELLS]. AB - OBJECTIVE: To summarize the research progress of the effects and mechanisms of Hedgehog signaling pathway in regulating bone formation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: The related literature concerning the regulations and mechanism of Hedgehog signaling pathway in osteogenic differentiation of BMSCs and bone formation in vivo, in vitro, and ex vivo studies in recent years was analyzed and summarized. RESULTS: The in vitro studies indicate that Hedgehog signaling pathway can promote osteogenic differentiation of BMSCs via activation of key molecules Smoothened (Smo) and Gli1 which are downstream of Hedgehog signaling, and Hedgehog signaling can activate mTORC2-Akt signaling by upregulation of insulin-like growth factor which has similar effects. Hedgehog signaling regulates osteoblast differentiation via activation of Hh-Smo-Ptch1-Gli signaling pathway and inhibition of Hh-Galphai-RhoA stress fibre signaling. Hedgehog signaling can regulate key molecules of osteogenesis Runx2 for promoting osteogenic differentiation and matrix mineralization by synergism of bone morphogenetic protein and Wnt signaling, and promotes bone formation and repair and healing for bone defect and bone graft model in vivo. CONCLUSIONS: Hedgehog signaling can regulate bone formation and osteogenic differentiation of BMSCs via activation of Hedgehog signaling and other signaling pathways. Hedgehog signaling pathway may be a potential target for developing treatment for bone related diseases of osteoporosis and fracture healing disorders. PMID- 29786350 TI - [ADVANCES IN ANATOMICAL REPAIR OF CHRONIC LATERAL ANKLE INSTABILITY]. AB - OBJECTIVE: To summarize the current status and progress of the treatment of chronic lateral ankle instability (CLAI). METHODS: The literature about the anatomical repair of CLAI at home and abroad was reviewed and summarized. RESULTS: Brostrom and its modified operations are the most common surgical treatment of CLAI. The operations showed satisfactory clinical outcomes in the short-, medium-, and long-term follow-up and low complication rate. Suture anchor technique and arthroscopic techniques are gradually used in Brostrom and its modified operations with satisfactory short-term effectiveness, but long-term effectiveness needs further observation because of the limitation of the short clinical application time. CONCLUSIONS: Brostrom and its modified operations are effective, convenient, and safe to treat CLAI. Based on the researches of biomechanics and dynamic anatomy, the more personalized design of the rehabilitation program is the further research direction. PMID- 29786351 TI - [RESEARCH PROGRESS OF PATHOLOGY OF ENDOCHONDRAL OSSIFICATION IN OSTEOARTHRITIS]. AB - OBJECTIVE: To summarize the research progress of pathological manifestations and mechanism of endochondral ossification in osteoarthritis (OA). METHODS: The literature about endochondral ossification, bone-cartilage remodeling in OA, and joints development was reviewed, analyzed, and summarized. RESULTS: Chondrocyte hypertrophy and apoptosis, vascular invasion, replication of the tidemark, thickening calcified cartilage, and thinning superficial cartilage are the characteristics of cartilage degeneration in OA. Articular cartilage and growth plate are similar in structure, and cartilage degeneration in OA is similar to a process of endochondral ossification of the growth plate. CONCLUSIONS: Loss of stability characterization from resting metabolic balance to a high conversion state of temporary cartilage in stimulation of abnormal mechanical stresses and cytokines would subsequently contributed to continual calcification and remodeling of articular cartilage, which may be the key link of the initiation and development of OA. PMID- 29786352 TI - [RESEARCH PROGRESS OF MAGNESIUM AND MAGNESIUM ALLOYS IMPLANTS IN ORTHOPEDICS]. AB - OBJECTIVE: To summarize the research and application progress of magnesium and magnesium alloys implants in the orthopedics. METHODS: The domestic and foreign related literature about the research progress and application of magnesium and magnesium alloys implants in the orthopedics was reviewed. RESULTS: Currently approved and commonly used metallic implants in orthopedics include stainless steels, titanium alloys, and chromium alloys having many disadvantages of poor biocompatibility, mismatch with the biomechanical properties of the bone tissue, and need of second surgical procedure to remove. Compared with traditional implants, magnesium and magnesium alloys have biomechanical properties closer to natural bone tissue, and in vivo degradation, which have the potential to serve as new biocompatible and degradable implants. Although magnesium and magnesium alloy materials have their own advantages, but the degradation rate is still too fast and so on. At present, the research and development of medical magnesium and magnesium alloy materials are to improve their corrosion resistance and control the rate of degradation. CONCLUSIONS: Magnesium and magnesium alloys have great potential as a implant material in the orthopedics, through further systematic and in-depth study, it is expected to become a new generation of degradation biological implant materials. PMID- 29786353 TI - [PROGRESS OF TREATMENT AND PREVENTION OF BREAST CANCER RELATED LYMPHEDEMA]. AB - OBJECTIVE: To review the progress of treatment and prevention of breast cancer related lymphedema. METHODS: The recent literature concerning treatment and prevention of breast cancer related lymphedema was extensively consulted and reviewed. RESULTS: The treatment of lymphedema is now based on complete decongestive therapy, supplemented with medicine and surgery. Those procedures have been proved to be safe and effective. Sentinel lymph node biopsy, axillary reverse mapping, and lymphaticovenous anastomoses have been used to decrease the incidence of lymphedema. They show promising effectiveness in short term, but the long-term effectiveness needs further tests. CONCLUSIONS: In clinical practice, many treatment methods are used to decrease lymphedema, and lymphedema prevention is playing an increasingly important role. Lymphaticovenous anastomoses shows a promising effectiveness in reducing lymphedema. PMID- 29786354 TI - [ACETABULUM RECONSTRUCTION AND TOTAL HIP ARTHROPLASTY FOR TREATMENT OF OLD CENTRAL DISLOCATION OF HIP JOINT]. AB - OBJECTIVE: To explore the clinical effect of total hip arthroplasty (THA) in the treatment of old central dislocation of the hip joint. METHODS: Between January 2010 and June 2014, 21 patients (21 hips) with old central dislocation of the hip joint underwent THA and autologous bone graft for acetabulum reconstruction. There were 13 males and 8 females, aged 60-75 years (mean, 67.4 years). The left hip was involved in 12 cases and the right hip in 9 cases, with a disease course of 1-20 years (mean, 9.6 years). The causes were falling from height in 6 cases, traffic accident in 9 cases, crushing in 4 cases, and others in 2 cases. Hip pain, limited activity, and lameness were the main clinical symptoms. Preoperative Harris score was 32.95+/-2.06 and visual analogue scale (VAS) was 8.14+/-0.73. RESULTS: Primary healing of incision was obtained in all patients. The patients were followed up 1.9-6.4 years (mean, 4.6 years). The X-ray films showed bone graft fusion at 4-24 months (mean, 12.5 months); there were no complications of grafted bone absorption, osteolysis, and infection. During follow-up, no prosthetic loosening or sinking, and no translucent zones around the prosthesis were observed. Harris score was significantly improved to 87.67+/ 2.01 at 1 week and 92.10+/-1.95 at 1 year; and VAS score was significantly decreased to 2.57+/-0.81 at 1 week and 0.19 +/-0.51 at 1 year (P<0.05). CONCLUSIONS: THA is an effective surgical treatment for old central dislocation of the hip joint, because it can restore normal hip rotation center and reconstruct the hip joint function. PMID- 29786355 TI - [USE OF SMARTPHONE IN ACETABULAR COMPONENT ANGLE MEASUREMENT DURING TOTAL HIP ARTHROPLASTY]. AB - OBJECTIVE: To evaluate the accuracy of using smartphone to measure the angle of acetabular component in total hip arthroplasty (THA). METHODS: Between June 2012 and September 2015, the acetabular abduction and anteversion angles were measured in 50 patients undergoing THA. There were 24 males and 26 females, aged 37 to 83 years (mean, 71 years). The left hip was involved in 22 cases and the right hip in 28 cases. Of 50 patients, 34 suffered from fracture of the femoral neck, and 16 suffered from avascular necrosis of the femoral head. Acetabular dysplasia was excluded in all cases. A smartphone was used to measure the acetabular abduction and anteversion angles during operation; standard Picture Archiving and Communication Systems (PACS) was used to measured the acetabular abduction and anteversion angles on the X-ray film at 1 week after operation. It was defined as positive that the component angle values by PACS measurement were greater than those by the smartphone measurement, whereas as negative. The two measurement methods were compared, and intra-observer variability was assessed by analyzing the intraclass correlation coefficient (ICC), the Mann-Whitney U-test was used to analyze difference. RESULTS: The ICC was 0.84 in the acetabular component angles by smartphone and PACS measurement methods. The acetabular component abduction angle was (44.02+/-1.33) degrees and the anteversion angle was (17.62+/-2.20) degrees by smartphone measurement. The acetabular component abduction angle was (44.74+/-4.05) degrees and the anteversion angle was (17.22+/-5.57) degrees by PACS measurement. There was no significant difference between two measurement methods (Z=-1.977, P=0.482; Z=-0.368, P=0.713). The acetabular component angle was in the safe zone in 44 cases; and the acetabular component anteversion angle was beyond safe range of 1 to 5 degrees , and the abduction angle was beyond safe range of 1 to 3 degrees in 6 cases. Intra-measurement variability was -21 to +10 degrees for the anteversion angle and -10 to + 9 degrees for the abduction angle, indicating that the acetabular component anteversion angle by smartphone measurement was greater than that by the PACS measurement, and the abduction angle was less than that by PACS measurement. CONCLUSIONS: Smartphone is a convenient tool to measure the acetabular component angle in THA. PMID- 29786356 TI - [EFFICACY OF SEQUENTIAL TREATMENT WITH ADDUCTOR CANAL NERVE BLOCK AND CYCLOOXYGENASE 2 SELECTIVE INHIBITOR AFTER TOTAL KNEE ARTHROPLASTY]. AB - OBJECTIVE: To investigate the efficacy of sequential treatment with adductor canal nerve block (ACNB) and cyclooxygenase 2 (COX-2) selective inhibitor (parecoxib and celecoxib) after primary total knee arthroplasty (TKA). METHODS: Between January 2015 and December 2015, 90 osteoarthritis patients who met the inclusion criteria were treated, and randomly divided into 3 groups:ACNB+COX-2 group (group A, n=30), COX-2 group (group B, n=30), and control group (group C, n=30). There was no significant difference in gender, age, body mass index, side, and osteoarthritis duration between groups (P>0.05), and the data were comparable. ACNB was used in group A at the end of TKA. Intravenous injection of parecoxib (40 mg per 12 hours) was administrated at the first three postoperative days, and followed by oral celecoxib (200 mg per 12 hours) until 6 weeks after operation in groups A and B; while placebo was given at the same time point in group C. Oral tramadol or intravenous morphine, as remedial measures, were introduced when patients had a visual analogue scale (VAS) score more than 4. The following indicators were compared between groups:the operative time, drainage volume at 24 hours after operation, length of hospital stay, and incidence of side effect; VAS pain scores, morphine consumption, range of motion (ROM) of the knee joint, and inflammatory cytokines levels at pre-operation and at 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation; morphine consumption within first 24 hours and at 24 hours to 6 weeks after operation; the American Hospital for Special Surgery (HSS) score at 1, 2, 4, and 6 weeks after operation; and the serum coagulation parameters at pre-operation, and at 1, 3, and 14 days after operation. RESULTS: The length of hospital stay was significantly shorter and the incidence of postoperative nausea and vomiting was significantly lower in groups A and B than group C (P<0.05). The VAS scores at rest (VASR) of groups A and B were significantly lower than that of group C at 1, 2, and 3 days after operation (P<0.05); difference in the VAS scores at walking (VASW) was significant between groups at 1 day after operation (P<0.05), and group A had the lowest VASW; and the VASW of groups A and B were significantly lower than that of group C at 2 and 3 days and at 1, 2, 4, and 6 weeks after operation (P<0.05). The difference in morphine consumption was significant between groups within the first 24 hours after operation (P<0.05), and group A exhibited the lowest consumption; and the morphine consumption in groups A and B was significantly lower than that in group C at 24 hours to 6 weeks after operation (P<0.05). Significant difference was found in HSS scores between groups at 1, 2, 4, and 6 weeks after operation, and group A showed the highest score (P<0.05). At 1 and 2 days after operation, group A showed the highest ROM (P<0.05), and ROM of groups A and B was significantly higher that of group C at 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation (P<0.05). Groups A and B were significantly lower than group C in the serum erythrocyte sedimentation rate at 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks, in C reactive protein levels at 1, 2, and 3 days, in interleukin 6 (IL-6) and TNF alpha levels at 1 day to 6 weeks, and in IL-8 level at 2 and 3 days (P<0.05). The drainage volume within the first 24 hours and the serum coagulation parameters within the 2 weeks after operation showed no significant difference between groups (P>0.05). CONCLUSIONS: Sequential treatment with ACNB and COX-2 selective inhibitor is a safe and effective approach for postoperative pain management after primary TKA, and it can alleviate postoperative pain, promote the joint function recovery, and reduce the risk of adverse reactions. PMID- 29786357 TI - [MINIMALLY INVASIVE TREATMENT OF POSTERIOR CRUCIATE LIGAMENT AVULSION FRACTURE IN A FLOPPY LATERAL POSITION]. AB - OBJECTIVE: To conclude the effectiveness of arthroscopy combined with Burks and SchaVer's approach in the treatment of posterior cruciate ligament (PCL) avulsion fractures in a floppy lateral position. METHODS: Between May 2010 and March 2014, 21 patients with PCL avulsion fractures were treated. There were 13 males and 8 females, aged 21 to 62 years (mean, 39.1 years). The causes included traffic accident injury in 10 cases, sports injury in 5 cases, and falling injury from height in 6 cases. The time from injury to hospital was 1-6 days (mean, 2.5 days). The results of posterior drawer test were all positive, and the results of anterior drawer test and lateral stress test were all negative. The Lysholm score was 28.0+/-5.5 before operation. And the American Orthopaedic Foot and Ankle Society (IKDC) score was 46.2+/-7.6 before operation. According to Meyer standards for fractures classification, 11 cases were rated as type II and 10 cases as type III. Arthroscopy was used to inspect and treat the intra-articular lesions, then avulsion fracture was fixed by Burks and SchaVer's approach in lateral position. Postoperative functional exercises were performed. RESULTS: Primary healing of incision was obtained, without nerve and vascular injury or joint infection. All patients were followed up 18-36 months (mean, 27.2 months). The X-ray films of the knee joint showed good fractures reduction and healing at 3 months after operation. The results of posterior drawer test and reverse Lachman test were negative. The knee range of motion was recovered to normal level. At last follow-up, the Lysholm score of the knee joint was significantly improved to 90.9+/-1.4 from preoperative one (t=54.584, P=0.000), and the IKDC score was significantly increased to 90.5+/-5.3 from preoperative one (t=15.638, P=0.000), including 19 cases of grade A and 2 cases of grade B. CONCLUSIONS: A combination of arthroscopy and Burks and SchaVer's approach for the treatment of PCL avulsion fractures in a floppy lateral position has the advantages of minimal invasion and safe approach, short operative time, and early postoperative rehabilitation exercises, so it can provide satisfactory function recovery of the knee joint. PMID- 29786358 TI - [MODIFIED POSTEROLATERAL COUNTER-CURVED INCISION WITH DOUBLE INTERMUSCULAR APPROACH IN TREATING POSTEROLATERAL TIBIAL PLATEAU FRACTURES]. AB - OBJECTIVE: To evaluate the effectiveness of the modified posterolateral counter curved incision with double intermuscular approach for the treatment of posterolateral tibial plateau fractures. METHODS: A retrospective analysis was made on the clinical data of 32 patients with posterolateral tibial plateau fractures between September 2012 and October 2014. There were 22 males and 10 females, aged 19 to 55 years (mean, 40.5 years). The causes of injury included traffic accident in 17 cases, falling from height in 9 cases, and falling in 6 cases. They had fresh closed fracture; injury to hospitalization time was 3 hours to 5 days (mean, 2 days). According to Schatzker tibial plateau fracture classification criteria, 20 cases were rated as type II, and 12 cases as type III. All patients underwent a modified posterolateral counter-curved incision with double intermuscular approach to expose tibial posterolateral condyle and anterolateral condyle. After a good visual control of fracture reduction, the anterolateral and posterolateral fractures were fixed with two-dimensional buttress plate respectively. RESULTS: The incisions healed at stage I, with no major neurovascular injury. According to radiological assessment of the DeCoster score, the results were excellent in 21 cases, and fair in 11 cases. All of the 32 patients were followed up 18 to 30 months (mean, 20.5 months). The X-ray films showed that all patients obtained good fracture union, and the mean time of fracture union was 12.3 weeks (range, 10-16 weeks). No fixation failure or no obvious loss of articular surface reduction was observed during follow-up. The range of motion of the affected knees was 2-135 degrees (mean, 120 degrees ). The mean American Hospital for Special Surgery (HSS) score was 90.05 (range, 83 96) at 18 months after operation. CONCLUSIONS: The modified posterolateral counter-curved incision with double intermuscular approach could fully expose posterolateral tibia plateau, and good fracture reduction and reliable fixation can be obtained under direct vision. PMID- 29786359 TI - [TREATMENT OF PRONATION EXTERNAL ROTATION ANKLE FRACTURE COMBINED WITH SEPARATION OF DISTAL TIBIOFIBULAR SYNDESMOSIS]. AB - OBJECTIVE: To evaluate the difference between using and not using syndesmotic screw to treat pronation external rotation (PER) ankle fracture combined with separation of distal tibiofibular syndesmosis. METHODS: Between April 2011 and October 2014, 46 cases of PER ankle fracture combined with separation of distal tibiofibular syndesmosis were treated, and syndesmotic screw was used in 24 cases (fixation group) and syndesmotic screw was not used in 22 cases (non-fixation group). There was no significant difference in gender, age, weight, cause of injury, side, injury to operation time, and fracture type between 2 groups (P>0.05). The time for full weight-bearing, fracture healing time, and complications were recorded after operation. Anteroposterior and lateral X-ray films were taken to measure the tibiofibular overlap (TBOL) and tibiofibular clear space (TBCS). Baird-Jackson score was used to evaluate functional recovery of the ankle. RESULTS: All incision healed by first intention without complications. The cases were followed up 13-18 months (mean, 15.2 months) in 2 groups. The time for full weight-bearing was 8-12 weeks (median, 11 weeks) in fixation group, which was significantly later than that in non-fixation group (range, 6-10 weeks; median, 8 weeks) (Z=-5.049, P=0.000). X-ray examination showed reduction of separation of distal tibiofibular syndesmosis. All fractures healed. The fracture healing time was (13.83+/-1.37) weeks in fixation group, and was (13.91+/-1.31) weeks in non-fixation group, showing no significant difference (t=-0.191, P=0.945). No separation of distal tibiofibular syndesmosis, delayed union, nonunion, loosening, or breakage of fixation devices was observed in 2 groups. There was no significant difference in TBOL, TBCS, Baird-Jackson score and the excellent and good rate between 2 groups (P>0.05). CONCLUSIONS: If the medial, lateral, and posterior structures of the ankle could be repaired according to injury, no significant influence on functional outcome of ankle or radiologic findings could be detected whether syndesmotic fixation is given or not in treating PER ankle fracture (exclude Maisonneuve fracture) combined with separation of distal tibiofibular syndesmosis. PMID- 29786360 TI - [CLINICAL APPLICATION OF AXIAL LOAD MECHANICAL TESTING IN REMOVING EXTERNAL FIXATOR AFTER TIBIA AND FIBULA FRACTURES SURGERY]. AB - OBJECTIVE: To explore the efficacy and safety of the axial load mechanical testing for removing external fixator. METHODS: Between January 2014 and August 2015, 27 patients with tibia and fibula fractures caused by trauma underwent an external fixation. Of 27 patients, 21 were male and 6 were female with the average age of 45 years (range, 19-63 years), including 7 cases of closed fracture and 20 cases of open fracture. X-ray film results showed spiral unstable fracture in 4 cases and comminuted unstable fracture in 23 cases. All patients underwent an external fixation. Bone nonunion occurred in 3 cases because of infection, and bone nonunion combined with bone defect occurred in 1 case, who received tibial osteotomy lengthening surgery. When X-ray film showed continuity high density callus formation at fracture site, axial load mechanical test was performed. If the axial load ratio of external fixator was less than 10%, the external fixator was removed. RESULTS: At 21-85 weeks after external fixation (mean, 44 weeks), axial load mechanical test was performed. The results showed that the axial load ratio of external fixation was less than 10% in 26 cases, and the external fixator was removed; at 6 weeks after removal of external fixator, the patients could endure full load and return to work, without re-fracture. The axial load ratio was 14% in 1 case at 85 weeks, and the X-ray film result showed that fracture did not completely heal with angular deformity; re-fracture occurred after removing external fixator, and intramedullary fixation was used. CONCLUSIONS: External fixator axial load mechanical testing may objectively reveal and quantitatively evaluate fracture healing, so it is safe and reliable to use for guiding the external fixator removal. PMID- 29786361 TI - [POSTEROLATERAL AND POSTEROMEDIAL APPROACHES FOR TREATMENT OF POSTERIOR Pilon FRACTURES IN ELDERLY PATIENTS]. AB - OBJECTIVE: To explore the clinical outcomes of open reduction and internal fixation by posterolateral and posteromedial approaches for treating posterior Pilon fractures in elderly patients. METHODS: Between August 2009 and August 2014, 20 elderly patients with posterior Pilon fractures were treated with open reduction and internal fixation by posterolateral and posteromedial approaches. There were 14 males and 6 females, aged from 66 to 83 years (mean, 72.7 years). The causes were falling injury in 11 cases and traffic accident injury in 9 cases. All the patients had lateral malleolus and medial malleolus fractures. The time from injury to operation was 7-14 days (mean, 8.6 days). The posterolateral incision was made to expose the posterolateral bone fragments of posterior malleolus and lateral malleolus fracture, and the posteromedial incision was made to expose the posteromedial fracture fragments of posterior malleolus and medial malleolus fracture. After reduction, fracture was fixed with locking plate or cannulated screw. All the patients began to functional exercise at 1 day after operation. RESULTS: The operation time was 60-110 minutes (mean, 92 minutes). The incisions healed primarily in all patients. There were no complications of incision dehiscence, infection, implant exposure, and nerve damage. No irritation sign of tendon was observed. All 20 cases were followed up for 12-18 months (mean, 13 months). The X-ray films showed that fracture healed at 3-9 months, with an average of 5.2 months. During follow-up period, no loosening or breakage of the implant was observed. The other patients could walk normally except 2 patients (over 80 years old) who could walk with crutch. According to American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, the results were excellent in 12 cases, good in 4 cases, and fair in 4 cases; the excellent and good rate was 80%. CONCLUSIONS: A combination of posterolateral approach and posteromedial approach for open reduction and fixation of posterior Pilon fractures can achieve satisfactory effect in elderly patients. It has the advantages of protecting ankle blood supply and avoiding the soft tissue necrosis and implants exposure. PMID- 29786362 TI - [EFFECTIVENESS OF SHARP TEETH HOOK PLATE FOR TREATMENT OF OLECRANON FRACTURES]. AB - OBJECTIVE: To investigate the effectiveness of sharp teeth hook plate by cutting for the treatment of olecranon fractures by comparison with Kirschner wire tension belt and locking plate. METHODS: Between January 2011 and April 2015, 32 cases of olecranon fractures were treated. Fracture was fixed with sharp teeth hook plate by cutting in 12 cases (trial group) and with Kirschner wire tension belt or locking plate in 20 cases (control group). There was no significant difference in gender, age, side and type of fracture, and time from injury to operation between 2 groups (P>0.05). The healing time of fractures and complications were recorded. At 1 year after operation, the subjective function results were evaluated according to Disability of Arm, Shoulder, and Hand (DASH) score, and objective function results by Mayo Elbow Score (MEPS); visual analogue scale (VAS) was used for elbow joint pain, and range of motion of flexion and extension of elbow joint was measured. RESULTS: All incisions healed by first intention, with no vascular and nerve injuries. All patients were followed up 12 36 months with an average of 18 months. All fractures healed, and there was no significant difference in the healing time between 2 groups (P>0.05). Loosening of Kirschner wire occurred in 2 cases of control group, but no loosening of internal fixation was observed in trial group after operation. There was no significant difference in the incidence of complications between 2 groups (P>0.05). The DASH, MEPS, VAS score, and range of motion of flexion in trial group were superior to those in control group, showing significant differences (P<0.05) at 1 year after operation. There was no significant difference in range of motion of extension between 2 groups (P>0.05). CONCLUSIONS: Sharp teeth hook plate for treatment of olecranon fractures overcomes the shortcomings that Kirschner wire tension is easy to slide and locking plate has a compression effect on triceps tendon, so it has good effectiveness. PMID- 29786363 TI - [EXPRESSION AND SIGNIFICANCE OF HYPOXIA INDUCIBLE FACTOR 1alpha IN RAT MODEL OF HETEROTOPIC OSSIFICATION AFTER Achilles TENOTOMY]. AB - OBJECTIVE: To explore the role and significance of hypoxia inducible factor lalpha (HIF-lalpha) and hypoxia microenvironment in the pathogenesis of post traumatic heterotopic ossification by detecting the expression of HIF-lalpha in rat model of heterotopic ossification after Achilles tenotomy. METHODS: A total of 140 male Sprague Dawley rats, aged 8-10 weeks, and weighing (210.1+/-10.6) g, were randomly divided into experimental group (n=70) and control group (n=70). In experimental group, the Achilles tendon was cut off and clamped to prepare post traumatic heterotopic ossification model; in control group, only Achilles tendon was exposed. The general condition of rats was observed after operation, and at 2, 3, 4, 5, 6, 7, 8, 10, 12, and 14 days after operation, the Achilles tendon tissue was harvested from 6 rats for gross observation, histological observation, and immunohistochemical staining observation, and real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of HIF lalpha gene and protein at different time points in 2 groups. The X-ray films were taken and histological examination was done at 10 weeks after operation to evaluate the formation of heterotopic ossification. RESULTS: During the experiment, 1 rat died in experimental group at 3 days after operation, and the other rats survived to the end of the experiment. Gross and histological staining showed that the Achilles tendon had no obvious change, with normal tendon structure in control group at each time point. In experimental group, atrophy and necrosis of Achilles tendon stump were observed, with infiltration of inflammatory cells; and the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells. When compared with control group, the HIF-lalpha mRNA and protein expressions were significantly increased in experimental group at each time point (P<0.05). Immunohistochemical staining showed that HIF-lalpha was positive in experimental group. According to the results of X-ray films and histological examination at 10 weeks after operation, heterotopic ossification was found in experimental group, but no heterotopic ossification in control group. CONCLUSIONS: The expression of HIF-lalpha significantly increases at early stage of post-traumatic heterotopic ossification after Achilles tenotomy, suggesting that the local hypoxia microenvironment plays an important role in the pathogenesis of heterotopic ossification. PMID- 29786364 TI - [COMPARISON OF EFFECTIVENESS BETWEEN PERCUTANEOUS VERTEBROPLASTY AND PERCUTANEOUS KYPHOPLASTY FOR TREATMENT OF OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURE WITH INTRAVERTEBRAL VACUUM CLEFT]. AB - OBJECTIVE: To compare the clinical efficacy and safety between percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture (OVCF) with intravertebral vacuum cleft (IVC). METHODS: Between January 2010 and December 2013, 68 patients with single OVCF and IVC were treated, and the clinical data were retrospectively analyzed. Of 68 patients, 48 underwent PVP (PVP group) and 20 underwent PKP (PKP group). There was no significant difference in age, gender, disease duration, fracture level, bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI), and preoperative radiological parameters between 2 groups (P>0.05). The intraoperative incidence of cement leakage, cement volume, and operative time were compared between 2 groups; VAS score was used for evaluation of back pain and ODI for evaluation of dysfunction; the incidence of adjacent vertebral fracture was observed within 2 years. The vertebral height and kyphotic angle were measured on X-ray films; the rate of vertebral compression (CR), reduction rate (RR), progressive height loss (PHL), reduction angle (RA), and progressive angle (PA) were calculated. RESULTS: There was no significant difference in cement volume and the incidence of cement leakage between 2 groups (P>0.05). The operative time in PVP group was shorter than that in PKP group, showing significant difference (t=-8.821, P=0.000). The mean follow-up time was 2.4 years (range, 2.0-3.1 years). The VAS scores and ODI were significantly reduced at 1 day, 1 year, and 2 years after operation when compared with preoperative scores (P<0.05), but there was no significant difference between different time points after operation in 2 groups (P>0.05). Adjacent vertebral fracture occurred in 5 cases (10.4%) of PVP group and in 2 cases (10.0%) of PKP group, showing no significant difference (chi2=0.003, P=0.963). BMD was significantly increased at 1 year and 2 years after operation when compared with preoperative BMD (P<0.05), but no significant difference was found between 2 groups (t=0.463, P=0.642; t=0.465, P=0.646). The X-ray films showed that CR and kyphotic angle were significantly restored at immediate after operation in 2 groups (P<0.05); but vertebral height and kyphotic angle gradually aggravated with time, showing significant difference between at immediate and at 1 and 2 years after operation (P<0.05); there was no significant difference in CR and kyphotic angle between 2 groups at each time point (P>0.05). RR, RA, PHL, and PA showed no significant difference between 2 groups (P>0.05). CONCLUSIONS: There is similar clinical and radiological efficacy between PVP and PKP for treatment of OVCF with IVC. Re-collapse could happen after operation, so strict observation and follow-up are needed. PMID- 29786365 TI - [COMPARISON OF SHORT SEGMENTAL FIXATION WITH AND WITHOUT FUSION IN TREATMENT OF THORACOLUMBAR BURST FRACTURE BY POSTERIOR APPROACH]. AB - OBJECTIVE: To compare the effectiveness of short segmental pedicle screw fixation with and without fusion in the treatment of thoracolumbar burst fracture. METHODS: A retrospective analysis was made on the clinical data of 57 patients with single segment thoracolumbar burst fractures, who accorded with the inclusion criteria between February 2012 and February 2014. The patients underwent posterior short segmental pedicle screw fixation with fusion in 27 cases (fusion group) and without fusion in 30 cases (non-fusion group). There was no significant difference in gender, age, cause of injury, time between injury and admission, fracture segment and classification, and neurologic function America Spinal Injury Association (ASIA) classification between 2 groups, which had the comparability (P>0.05). The operative time, blood loss, and hospitalization days were compared between 2 groups. The height of the injured vertebra, the kyphotic angle, and the range of motion (ROM) were measured on the X-ray film. The functional outcomes were evaluated by using the Greenough low back outcome score and the visual analogue scale (VAS) for back pain. The neurologic functional recovery was assessed by ASIA grade. RESULTS: The operative time was significantly shortened and the blood loss was significantly reduced in the non-fusion group when compared with the fusion group (P<0.05), but no significant difference was found in hospitalization days between 2 groups (P>0.05). The patients were followed up for 2.0-3.5 years (mean, 3.17 years) in the fusion group and for 2-4 years (mean, 3.23 years) in the non-fusion group. X ray films showed that 2 cases failed bone graft fusion, the fusion time was 12-17 weeks (mean, 15.6 weeks) in the other 25 cases. Complication occurred in 2 cases of the fusion group (1 case of incision deep infection and 1 case of hematoma at iliac bone donor site) and in 1 case of the non-fusion group (fat liquefaction); primary healing of incision was obtained in the others. The Cobb angle, the height of injured vertebrae showed no significant difference between 2 groups at pre-operation, immediate after operation, and last follow-up (P>0.05). The ROM of injured vertebrae showed no significant difference between 2 groups at 1 year after operation (before implants were removed) (P>0.05). The implants were removed at 1 year after operation in all cases of the non-fusion group, and in 11 cases of the fusion group. At last follow-up, the ROM of injured vertebrae in the non-fusion group was significantly higher than that in the fusion group (P<0.05), but no significant difference was found in Greenough low-back outcome score, VAS score, and ASIA grade between 2 groups (P>0.05). CONCLUSIONS: Fusion is not necessary when thoracolumbar burst fracture is treated by posterior short segmental pedicle screw fixation, which can preserve regional segmental motion, shorten the operative time, decrease blood loss, and eliminate bone graft donor site complications. PMID- 29786366 TI - [POSTEROLATERAL FUSION AND PEDICLE SCREW FIXATION FOR TREATING OLD THORACOLUMBAR FRACTURE COMBINED WITH KYPHOSIS IN ELDERLY PATIENTS]. AB - OBJECTIVE: To investigate the clinical efficacy and the indications of posterolateral fusion and pedicle screw short-segment fixation via injured vertebra for treating old thoracolumbar fracture combined with kyphosis in elderly patients. METHODS: Between January 2012 and December 2014, 24 patients with old thoracolumbar fracture and kyphosis received posterolateral fusion and pedicle screw short-segment fixation via injured vertebra. Of 24 cases, 8 were male and 16 were female with an average age of 66.3 years (range, 56-79 years). The mean disease course was 17.5 months (range, 5-36 months). There were 13 cases of osteoporosis, 9 cases of osteopenia, and 2 cases of normal bone. The visual analogue scale (VAS) was 6.53+/-0.95, and Oswestry disability index (ODI) was 52.63%+/-5.74% preoperatively. The thoracolumbar kyphosis located at T10 to L2, and the kyphotic Cobb angle was (28.79+/-5.04) degrees before operation. RESULTS: The operation was completed successfully without related complications. The operative time was 1.2-2.3 hours (mean, 1.6 hours), and intraoperative blood loss was 80-210 mL (mean, 158 mL). No nerve injury occurred. Poor healing of incision was observed in 1 patient with diabetes, and primary healing of incision was obtained in the other patients. Nineteen patients were followed up 6-30 months (mean, 14.4 months), and there were 2 deaths. Pain relief and function recovery were obtained in 19 patients after operation. The VAS score and ODI were significantly decreased to 2.4+/-0.7 and 32.14%+/-5.12% at last follow-up (t=8.542, P=0.000; t=9.826, P=0.000). The kyphotic Cobb angle was significantly decreased to (21.23+/-4.30) degrees at immediate after operation (P<0.05) and to (23.68+/-4.35) degrees at last follow-up (P<0.05), but no significant difference was found between at immediate and last follow-up (P>0.05). No loosening or breakage of internal fixation was observed during follow-up. CONCLUSIONS: Posterolateral fusion and pedicle screw short-segment fixation via injured vertebra is a safe and effective treatment for elderly patients with old thoracolumbar fracture combined with kyphosis (Cobb angle less than 40 degrees ). PMID- 29786367 TI - [V-Y ADVANCEMENT OF MEDIAL GASTROCNEMIUS MUSCLE FLAP FOR REPAIRING SOFT TISSUE DEFECTS IN MIDDLE AND LOWER SEGMENTS OF ANTERIOR TIBIA]. AB - OBJECTIVE: To investigate the effectiveness of V-Y advanced medial gastrocnemius muscle flap to repair soft tissue defects in the middle and lower segments of the anterior tibia. METHODS: Between March 2008 and March 2014, 8 patients with skin and soft tissue defects of the anterior tibia were treated, including 6 males and 2 females with an average age of 36.2 years (range, 28-47 years). The soft tissue defects located at the left leg in 5 cases and at the right leg in 3 cases. The causes included traffic accident injury in 6 cases, and heavy pound injury in 2 cases. Three cases had simple soft tissue defects, and the disease course was 5 hours, 6 days, and 14 days, respectively. Five cases had soft tissue defects and fractures, including 1 case of Pilon fracture, and 4 cases of middle and distal tibial fracture; open reduction and internal fixation were performed in 3 cases, the implementation of external fixation in 2 cases; 1 case had chronic osteomyelitis at 11 months after operation, and 4 cases had skin necrosis and wound infection at 1 to 2 weeks after operation; the duration was 1-12 months (mean, 3.4 months). The skin and soft tissue defect area was 5.2 cm*2.5 cm to 13.0 cm*5.5 cm. Debridement was given, and vacuum sealing drainage was used in 6 cases, and then V-Y advancement of medial gastrocnemius muscle flap was used to cover the wound. Because of light wound contamination, the wound was repaired by the flap after emergency debridement in 1 case; 1 patient with osteomyelitis underwent flap repair at immediate after sensitive antibiotics use and debridement. The size of medial gastrocnemius muscle flaps ranged from 15 cm*6 cm to 26 cm*15 cm. The donor site was sutured in 3 cases or repaired with skin graft in 5 cases. RESULTS: One case had tension blisters in the distal flap, which was cured after symptomatic treatment. The flap and skin graft survived, and primary healing was obtained in the other cases. Seven patients were followed up 6-18 months (mean, 9 months). The texture and appearance of the flaps were satisfactory. At 6 months after operation, two-point discrimination ranged from 12 to 18 mm (mean, 16 mm). The plantar flexion was weaker than that of normal side, but the patients could normally walk and had normal gait. CONCLUSIONS: The V-Y advancement of medial gastrocnemius muscle flap is recommendable to repair soft tissue defects in the middle and lower segments of the anterior tibia for the advantages of reliable blood supply, simple operation, high survival rate of the flap, and satisfactory appearance. PMID- 29786368 TI - [SURGICAL TREATMENT OF CONGENITAL TYPE V THUMB SYNDACTYLY]. AB - OBJECTIVE: To study the effectiveness of surgical treatment of congenital type V thumb syndactyly. METHODS: Between March 2010 and May 2015, 12 cases of congenital type V thumb syndactyly were treated. There were 7 males and 5 females, aged from 1 to 25 years (mean, 8 years). The right thumb was involved in 8 cases, and the left thumb in 4 cases. There were 2 cases of radial type, and 10 cases of ulnar type. The basement of polydactylism was far away from the carpometacarpal joint in 7 cases, and was close to the carpometacarpal joint in 5 cases (slight ulnar deviation in 1 case). X-ray films showed that the main first thumb metacarpal bone and trapezium fitted well, and 2 cases had the first metacarpal bone deformity. Preoperative individualized treatment plan was made, and polydactylism was excised by the "S" or "Z" incision and simultaneous reconstruction of thenar muscle insertions or adductor muscle insertions was performed; if necessary, wedge osteotomy was used for correction. RESULTS: All incisions healed by first intention with no complication. All cases were followed up 6 to 24 months (mean, 12 months). The thumb appearance, flexion and extension, the function of opposition, abduction function were improved significantly in 11 cases with no scar contracture deformity, small first web space, and deviation deformity. One case had slightly narrow first web space. According to hand function criterion, the results were excellent in 10 cases, good in 1 case, poor in 1 case; excellent and good rate was 91.7%. CONCLUSIONS: Based on the condition of the type V thumb syndactyly, the individualized treatment plan is made, which can better restore the shape and function of the thumb. PMID- 29786369 TI - [COMBINED THREE OPERATIONS FOR ONE STAGE DEFECTS REPAIR AFTER RESECTION OF LARGE XANTHELASMA PALPEBRARUM WITH EPICANTHUS]. AB - OBJECTIVE: To investigate the effectiveness of combined three operations (rotated total upper eyelid skin flap, construction of double eyelid, and "Z" flap epicanthal plasty) for one stage defect repair after resection of xanthelasma palpebrarum with epicanthus. METHODS: Between December 2013 and December 2015, 12 female patients with large xanthelasma palpebrarum and epicanthus underwent rotated total upper eyelid skin flap, construction of double eyelid, and "Z" flap epicanthal plasty for one stage defect repair. The age ranged from 36 to 59 years (mean, 43 years). The course of disease was 3 to 16 years, with an average of 11 years. The initial resection was performed in 6 cases, second resection of residual xanthelasma palpebrarum in 4 cases, and 2 cases had recurrence after resection. The maximum diameter of xanthelasma palpebrarum was 0.5-1.3 cm (mean, 1.0 cm). According to CHE Junmin et al criterion, epicanthus was rated as mild in 7 cases, moderate in 3 cases, and severe in 2 cases. The blood lipid level was in normal range. RESULTS: Primary healing of incision was obtained, and the flaps survived in all patients; no complication occurred. Scar hyperplasia was found in 4 cases at 1 month after operation, and the comprehensive treatment of scar was performed. All patients were followed up for 3 months to 2 years, with an average of 1.5 years. Double eyelid effects were good, and no xanthelasma palpebrarum recurred. CONCLUSIONS: A combination of rotated total upper eyelid skin flap, construction of double eyelid, and "Z" flap epicanthal plasty is an effective operative procedure to repair defect after resection of xanthelasma palpebrarum with epicanthus; and better curve of double eyelid, better shape of endocanthion, and less tension of flap can be got. PMID- 29786370 TI - [CLITOROPLASTY FOR GENITAL VIRILIZATION IN GIRLS WITH CONGENITAL ADRENAL HYPERPLASIA]. AB - OBJECTIVE: To investigate the effectiveness of clitoroplasty of reserving the clitoris dorsal neurovascular bundle and the ventral complete urethral plate for genital virilization in girls with congenital adrenal hyperplasia (CAH). METHODS: Between June 2000 and October 2015, 27 girls with genital virilization were treated with clitoroplasty of reserving the clitoris dorsal neurovascular bundle and the ventral complete urethral plate. The chromosomal karyotype was 46, XX in all patients, whose age ranged from 3 to 11 years (mean, 3.9 years). According to Parder's virilization scale, 5 cases were classified as stage II, 18 cases as stage III, and 4 cases as stage IV. The hormone tests showed decreased cortisol level and increased testosterone and 17-hydroxyprogesterone levels. They were diagnosed with non-salt-wasting CAH. RESULTS: All of the patients underwent clitoroplasty successfully. The mean operation time was 74 minutes (range, 58-95 minutes). Incision healed primarily. The patients were followed up 6 months to 10 years (median, 19 months). The external genitalia had good appearance, without necrosis of flap and the glans clitoris, abnormal sensation of the glans clitoris, or clitorism recurrence. Five girls had breast development and normal menstrual cycle during adolescence, and 1 patient who was followed up for 10 years gave birth to a son. CONCLUSIONS: Clitoroplasty of reserving the clitoris dorsal neurovascular bundle and the ventral complete urethral plate is a relatively ideal method for treating genital virilization in girls. It has less complications, good aesthetic and functional results. There are satisfactory outcomes when combining with the endocrine treatment. PMID- 29786371 TI - [ESTABLISHING AN ANIMAL MODEL OF DEFECATION RECONSTRUCTION AFTER SPINAL CORD INJURY IN RATS BY MECHANICAL POLISHING METHOD]. AB - OBJECTIVE: To study the feasibility and advantages of preparing an animal model of defecation reconstruction after spinal cord injury in rats by mechanical polishing method. METHODS: Forty adult female Sprague Dawley rats (weighing, 250 300 g) were randomly divided into 2 groups (n=20). The lamina was opened by mechanical polishing method to expose the cauda equina in experimental group, then bilateral L5 and S1 nerve roots end-to-end anastomosis was done under 10 times microscope, and finally cauda equina between the L5 and L6 (except S1) was cut. The lamina was opened by traditional bites method in control group, and the other treatment methods were in agreement with the experimental group. The operative time, intra-operative blood loss, and situation of rats at postoperative 3 days were recorded. RESULTS: The operative time of experimental group[(93.05+/-7.60) minutes] was significantly shorter than that in control group[(131.30+/-11.68) minutes] (t=12.279, P=0.000); intra-operative blood loss in experimental group[(4.33+/-0.46) mL] was significantly lower than that in control group[(7.36+/-0.58) mL] (t=18.293, P=0.000). At 3 days after operation, 18 rats (90%) survived in experimental group, and 12 rats (60%) survived in control group; difference was significant in the survival rate between 2 groups (chi2=4.800, P=0.028). CONCLUSIONS: To establish an animal model of defecation reconstruction after spinal cord injury in rats by mechanical polishing method is feasible, and it has shorter operative time, less blood loss, and lower postoperative mortality than the traditional bites method. But there is a certain learning curve and requirement to master microsurgical techniques. PMID- 29786372 TI - [EXPRESSION AND SIGNIFICANCE OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR gamma IN KELOID]. AB - OBJECTIVE: To investigate the expression and significance of peroxisome proliferator activated receptor gamma(PPAR-gamma) in human keloid. METHODS: Twenty-three keloid samples were harvested from the patients undergoing keloid and auto-skin grafting operation as the experimental group (keloid group), and the residual normal skin after auto-skin grafting operation was collected as the control group. The expression of PPAR-gamma protein was examined by immunohistochemistry staining in both keloid and normal skin. Referring to Shimizu immunohistochemical standard, the result was graded; the positive rate of samples and the rate of positive cells were calculated. RESULTS: Immunohistochemistry staining showed that PPAR-gamma protein was expressed in both keloid and normal skin. In keloid, it located in the pricle cell layer, and granular layer of epidermis, and the dermal vessel; the degree of dyeing was very light. However, in normal skin, it located in the base layer of epidermis, dermal vessel walls, sweat glands and sebaceous glands; the dyeing degree was deeper. Immunohistochemical staining score in the keloid group (2.65+/-0.78) was significantly lower than that in the control group (3.65+/-1.19) (t=5.030, P=0.000). The positive rate of samples in the keloid group (52.17%, 12/23) was significantly lower than that in the control group (82.61%, 19/23) (chi2=4.847, P=0.028). The rate of positive cells was 46.04%+/-8.61% in the keloid group, which was significantly lower than that in the control group (59.39%+/-11.26%) (t=5.974, P=0.000). CONCLUSIONS: Compared with normal skin, the expression of PPAR-gamma protein in keloid is down-regulated in in human keloid, indicating that PPAR-gamma may be related to the formation of keloid. PMID- 29786373 TI - [EFFECT OF ACTIVED RAW264.7 INDUCED BY H2O2 ON MIGRATION, PROLIFERATION AND OSTEOGENESIS GENE EXPRESSION OF MC3T3-E1]. AB - OBJECTIVE: To explore the effect of H2O2-actived RAW264.7 macrophages on the migration, proliferation, and osteogenesis gene expression of MC3T3-E1 in mice. METHODS: MC3T3-E1 cells and RAW264.7 cells were cultured to the 7th generation. RAW264.7 macrophages were stimulated with 0, 25, 50 and 100 MUmol/L H2O2, the cell proliferation rate was detected by MTS at 1, 3, and 6 hours after stimulated, and superoxide dismutase (SOD) content by SOD assay kit at 1 hour after stimulated. The appropriate concentration and action time of H2O2-actived RAW264.7 were obtained. The supernatant of RAW264.7 macrophages stimulated by H2O2 or not was collected at 24 hours. Then, the supernatant was used to culture MC3T3-E1 cells in groups B (not stimulated by H2O2) and C (stimulated by H2O2), and DMEM was used as a control in group A. The migration of MC3T3-E1 cells was detected at 12 and 24 hours by cell scratch test, the proliferation of MC3T3-E1 cells at 24, 48, and 72 hours by MTS assay. MC3T3-E1 cells were cultured with only complete medium in blank control group, with complete medium containing 50 MUg/mL vitamin C + 10 nmol/L beta sodium glycerophosphate in positive group, normal control group (adding the supernatant not stimulated by H2O2), and experimental group (adding the supernatant stimulated by H2O2). At 3, 7, and 14 days, RT-PCR was used to determine the osteogenesis related mRNA expressions of alkaline phosphatase (ALP), Runx2, osteopontin (OPN), osteocalcin (OC), bone sialoprotein (BSP), and collagen type I (COL-I). RESULTS: The results of MTS and SOD assay showed that the appropriate concentration and action time of H2O2 actived RAW264.7 macrophages were 25 MUmol/L and 1 hour, respectively. MTS assay showed that the proliferation rate of MC3T3-E1 cells was significant higher in groups B and C than group A (P<0.05), in group B than group C, and significant difference was shown between groups at 2 and 3 days (P<0.05). The cell scratch test indicated that the migration of MC3T3-E1 cells was significantly faster in groups B and C than group A, and in group C than group B at 12 hours (P<0.05); many migrated cells were observed in all scratch sites of groups B and C at 24 hours. When compared with positive control group, the mRNA expressions of ALP, Runx2, OC and BSP in experimental group were significantly down-regulated at 7 and 14 days (P<0.05). When compared blank control group, the mRNA expressions of OPN and COL-I in experimental group were significantly down-regulated at 7 and 14 days (P<0.05). CONCLUSIONS: The appropriate concentration and action time of H2O2 actived RAW264.7 macrophages are 25 MUmol/L and 1 hour. The H2O2-actived RAW264.7 cells can promote MC3T3-E1 cells migration, and suppress MC3T3-E1 cells proliferation and expressions of osteogenesis related genes. PMID- 29786375 TI - [RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING TECHNIQUE FOR SPINAL IMPLANTS]. AB - OBJECTIVE: To summarize the current research progress of three-dimensional (3D) printing technique for spinal implants manufacture. METHODS: The recent original literature concerning technology, materials, process, clinical applications, and development direction of 3D printing technique in spinal implants was reviewed and analyzed. RESULTS: At present, 3D printing technologies used to manufacture spinal implants include selective laser sintering, selective laser melting, and electron beam melting. Titanium and its alloys are mainly used. 3D printing spinal implants manufactured by the above materials and technology have been successfully used in clinical. But the problems regarding safety, related complications, cost-benefit analysis, efficacy compared with traditional spinal implants, and the lack of relevant policies and regulations remain to be solved. CONCLUSIONS: 3D printing technique is able to provide individual and customized spinal implants for patients, which is helpful for the clinicians to perform operations much more accurately and safely. With the rapid development of 3D printing technology and new materials, more and more 3D printing spinal implants will be developed and used clinically. PMID- 29786374 TI - [EXPERIMENTAL STUDY ON LENTIVIRUS-MEDIATED MULTI-GENES CO-TRANSFECTION IN BONE MARROW MESENCHYMAL STEM CELLS FOR TREATMENT OF KNEE OSTEOARTHRITIS IN CYNOMOLGUS MONKEY]. AB - OBJECTIVE: To observe the effect of lentivirus-mediated cyclooxygenase 2 (COX-2) and Aggrecanase-1 silencing and insulin-like growth factor 1 (IGF-1) in BMSCs after injecting into the knee joint cavity in cynomolgus monkeys with knee osteoarthritis (OA). METHODS: BMSCs were isolated from the bone marrow of 10 donors. The lentivirus vector expressing genes of COX-2, Aggrecanase-1, and IGF-1 were constructed, and transfected into the third generation human BMSCs at 40 multiplicity of infection (virus group); BMSCs transfected with lentivirus-empty vector served as blank-virus group. The growth status and number of BMSCs were observed under inverted phase contrast microscope, and normal BMSCs were used as normal control group. At 1 week after transfected, the mRNA expressions of COX-2, Aggrecanase-1, and IGF-1 were detected with RT-PCR. Nine 3-year-old cynomolgus monkeys were selected to establish the OA model according to Hulth modeling method, and were randomly divided into 3 groups (n=3). At 6 weeks after remodeling, the right knee joint cavity was injected accordingly with 1 mL BMSCs (about 1*107 cells) in virus group and blank-virus group, with 1 mL of normal saline in the blank control group; the left knee served as normal controls. The general condition was observed after injection; at 1, 4, and 6 weeks, the concentrations of prostaglandin E2 (PGE2), IL-1, Aggrecanase-1, and IGF-1 of double knee liquid were detected with ELISA; at 6 weeks, MRI, general observation, histology method, and immunohistochemistry method were used to detect the knee cartilage changes and the expressions of COX-2, Aggrecanase-1, and IGF-1 were measured with RT-PCR. RESULTS: No significant difference was found in cell morphology and growth curve between 2 groups after transfection. By RT PCR, COX-2, and Aggrecanase-1 expressions were significantly reduced, IGF-1 expression was significantly increased in virus group when compared with normal control group and the blank-virus group (P<0.05). All monkeys survived to the end of the experiment after injection. When compared with blank-virus group and blank control group, the concentrations of PGE2, Aggrecanase-1, and IL-1 significantly decreased and the concentration of IGF-1 significantly increased in the virus group (P<0.05), but the indicators in 3 groups were significantly higher than those in the normal control group (P<0.05). MRI showed that abnormal articular surface with high density could be found in virus group, blank-virus group, and blank control group, while the virus group had the minimum area. Gross observation and histological observation showed that the cartilage morphology of virus group, blank-virus group, and blank control group was accordance with early OA articular cartilage changes, but virus group was better than blank-virus group and blank control group in repair degree, whose improved Pineda score was significantly lower (P<0.05). Immunohistochemical staining showed that the virus group had deeper dyeing with occasional brown particles and more chondrocytes than blank-virus group and blank control group. By RT-PCR, COX-2 and Aggrecanase 1 mRNA expressions of cartilage in virus group were significantly decreased, and IGF-1 expression was significantly increased when compared with blank control group and the blank-virus group (P<0.05). CONCLUSIONS: Lentivirus-mediated multi genes co-transfection in BMSCs can inhibit the expressions of COX-2 mRNA and Aggrecanase-1 mRNA, and enhance the IGF-1 mRNA expression, which decreases the concentration of inflammatory factors, and protects the joint cartilage effectively. PMID- 29786376 TI - [RESEARCH PROGRESS OF SURGICAL PROCEDURES FOR CUBITAL TUNNEL SYNDROME]. AB - OBJECTIVE: To summarize the clinical research progress of surgical procedures for cubital tunnel syndrome. METHODS: The related literature on surgical procedures for cubital tunnel syndrome was summarized and analyzed. RESULTS: Multiple surgical procedures have been applied to treat cubital tunnel syndrome, including simple decompression, subcutaneous transposition, submuscular transposition, medial epicondylectomy, intramuscular transposition, and ulnar groove plasty. Each procedure has its own advantages and disadvantages. With the development of minimally invasive surgical technique, endoscope-assisted surgery has been gradually applied to treat cubital tunnel syndrome. CONCLUSIONS: Optimal surgical procedure remains controversial and individualized treatment decision based on patient's clinical conditions is recommended. PMID- 29786377 TI - [RESEARCH PROGRESS OF SUPERCAPSULAR PERCUTANEOUSLY ASSISTED TOTAL HIP IN MINIMALLY INVASIVE TOTAL HIP ARTHROPLASTY]. AB - OBJECTIVE: To summarize the research progress of Supercapsular percutaneously assisted total hip (SuperPath) in minimally invasive total hip arthroplasty (THA). METHODS: The related literature on SuperPath in terms of its history, indications, contraindications, surgical technique, and curative effect was summarized and analyzed. RESULTS: SuperPath for minimally invasive THA is an approach that makes use of the interval between the gluteus medius and piriformis, it can eliminate the need to cut through any muscle and tendon. In comparison to conventional surgery, the SuperPath has the advantages of less soft tissue injury, quicker post-operative recovery, shorter hospitalization days, and the short-term curative effect is good. But there are also some disadvantages of narrower indications, need of special equipment and higher prosthesis malposition. CONCLUSIONS: The SuperPath can reduce surgical trauma and the risk of postoperative dislocation and other complications, so the purpose of early rapid rehabilitation is achieved. However, the time of its clinical application is still short, so the long-term effectiveness and related complications should be further observed. PMID- 29786378 TI - [RESEARCH PROGRESS OF PATHOGENESIS MECHANISM OF SPINAL DEFORMITY IN NEUROFIBROMATOSIS TYPE 1]. AB - OBJECTIVE: To review the research progress of pathogenesis mechanism of spinal deformity in neurofibromatosis type 1 (NF1). METHODS: Recent literature concerning the pathogenesis mechanism of spinal deformity in NF1 was extensively reviewed, and current developments of the correction of spinal deformity and NF1 and the pathogenesis mechanism were summarized. RESULTS: The pathogenesis mechanism of spinal deformity in NF1 is not yet clearly known. Current theories include erosion and stress of neurofibromas, melatonin-related decreased contractility of paraspinal muscles, osteopenia and osteoporosis, sexual precocity and mesoderm dysplasia. CONCLUSIONS: The clinical manifestations of NF1 may cause the spinal deformities in patients with NF1. The research of pathogenesis mechanism of spinal deformity in NF1 will be conducive to further understanding, diagnosis and treatment of NF1-related spinal deformity. PMID- 29786379 TI - [FEASIBILITY AND SHORT-TERM EFFECTIVENESS ANALYSIS OF MODIFIED RADICAL RESECTION AND RECONSTRUCTION SURGERY FOR MALIGNANT PROXIMAL HUMERUS TUMOR]. AB - OBJECTIVE: To explore the feasibility and short-term effectiveness of the modified radical resection and reconstruction in the treatment of malignant proximal humerus tumor. METHODS: The relevant anatomic data from 30 normal adult shoulder joint MRI were measured to analyze the feasibility of modified radical resection and reconstruction surgery in the treatment of malignant proximal humerus tumor. Five patients with malignant proximal humerus tumor were treated by using the modified radical resection and reconstruction surgery between March 2012 and January 2016. There were 1 male and 4 females, aged from 9 to 69 years (median, 46 years). There were 4 cases of osteosarcoma (Enneking IIA in 2 cases and Enneking IIB in 2 cases) and 1 case of metastatic carcinoma (moderately differentiated adenocarcinoma). The disease duration was 7 to 12 months (mean, 9 months). Recurrence of tumor was observed after operation, and the shoulder function was assessed according to Enneking skeletal muscle tumor function scoring system. RESULTS: Radiographic results showed that modified radical resection and reconstruction surgery was feasible, which was in allowable range of the maximum longitudinal diameter (<29.8 mm) and depth (<4 mm). The operation was successfully completed in all 5 cases, and pathological examination suggested that purposes of radical resection had achieved. All patients were followed up 3 to 49 months (mean, 15.6 months). One patient had local recurrence at 12 months after operation, and a shoulder joint amputation was performed; the other 4 patients had good prosthesis survival. At last follow-up, the function of the shoulder joint was obviously recovered when compared with preoperative function; Enneking's skeletal muscle tumor function score was 25.8 points (range, 24 to 27 points). CONCLUSIONS: Modified radical resection and reconstruction surgery is feasible for the treatment of proximal humerus tumor, and it can maintain a good early shoulder function. PMID- 29786380 TI - [LONG-TERM EFFECTIVENESS OF TRANSPIANTATION OF ILIAC BONE FLAP PEDICLED WITH DEEP ILIAC CIRCUMFLEX VESSELS FOR AVASCULAR NECROSIS OF FEMORAL HEAD AT STAGE II AND III]. AB - OBJECTIVE: To assess the long-term effectiveness of the transplantation of iliac bone flap pedicled with deep iliac circumflex vessels for treating avascular necrosis of femoral head (ANFH) at Ficat stage II and III. METHODS: Thirty-two cases (43 hips) of ANFH underwent iliac bone flap transplantation pedicled with deep iliac circumflex vessels between October 2000 and February 2006, and the clinical data were retrospectively reviewed. Of 32 cases, 27 were male (38 hips), and 5 were female (5 hips), aged 21-52 years (mean, 36.6 years); there were 8 cases (11 hips) of hormone ANFH, 18 cases (23 hips) of alcoholic ANFH, and 6 cases (9 hips) of idiopathic ANFH. The disease duration ranged from 2-52 months (mean, 8.2 months). According to Ficat staging criteria, 26 hips were classified as stage II and 17 hips as stage III. The preoperative Harris hip score (HSS) was 68.2+/-8.4. The HHS scores and X-ray photograph were compared between at pre- and post-operation to assess the outcomes clinically and radiologically. RESULTS: All incisions healed by first intention. Two cases had numbness of the lateral femoral skin. Four patients (6 hips) failed to be followed up, and the other 28 cases were followed up 98-187 months (mean, 129.3 months). Five patients (6 hips) showed aggravation or no relief with progression to stage IV at 8-69 months, who received total hip arthroplasty. The 10-year survival rate was 83.78% (31/37). The HHS score was significantly increased to 86.7+/-9.0 at last follow-up (t= 48.313, P=0.000). The hip function was excellent in 9 hips, good in 13 hips, and fair in 9 hips, and the success rate was 75.68%. Radiographic examination showed signs of bone remodeling at 6-8 weeks. After bone healing, the femoral head density gradually became uniform. Until last follow-up, ANFH progressed from Ficat stage II to III in 5 hips, from Ficat stage II to IV in 3 hips, and from Ficat stage III to IV in 3 hips; complete hip shape, continuous Shenton line, and normal joint space were observed in the other 26 hips, and the radiographic success rate was 70.27% (26/37). CONCLUSIONS: The pedicled iliac bone flap transplantation for ANFH at Ficat stage II and III can provide good osteogenesis and vascular reconstruction of the femoral head. The long-term follow-up effectiveness is satisfactory. PMID- 29786381 TI - [EARLY EFFECTIVENESS COMPARISON OF HEMIARTHROPLASTY BY MINIMAL INVASIVE Supercap APPROACH AND BY CONVENTIONAL APPROACH FOR ELDERLY FEMORAL NECK FRACTURE]. AB - OBJECTIVE: To compare the early clinical and radiographic outcomes of hemiarthroplasty by a minimal invasive Supercap approach and by a conventional approach for elderly displaced femoral neck fractures. METHODS: Between January and June 2015, 70 geriatric patients with displaced femoral neck fracture underwent cementless bipolar hemiarthroplasty by minimally invasive Supercap approach (group A, n=35) or by posterolateral approach (group B, n=35). One patient was excluded from the study in group B because of too wide femur cavity. There was no significant difference in gender, age, body mass index, fracture cause, time from fracture to operation, fracture side, fracture classification, and preoperative visual analogue scale (VAS), and hemoglobin-level between the 2 groups (P>0.05). The operation time, intraoperative blood loss, incision length, and complications were recorded. The early clinical evaluations included timed up and go test (TUG), hemoglobin-level, VAS score, and satisfaction. The anteroposterior and lateral X-ray films were taken to measure the stem alignment, difference in leg length, and difference in femoral offset. RESULTS: All the patients were followed up 6-11 months (mean, 7.32 months). No patients died during follow-up. There was no significant difference in operation time and intraoperative blood loss between the 2 groups (P>0.05). The incision length of group A was significantly smaller than that of group B (P<0.05). One patient had delayed union of incision in group A (2.86%); 2 patients had deep vein thrombosis in group B (5.88%); and there was no significant difference in the complication rate (chi2=0.764, P=0.512). The postoperative hemoglobin level showed no significant difference between the 2 groups (P>0.05). Group A had lower VAS score and higher subjective satisfaction than group B, showing significant difference at 1, 5, and 14 days after operation (P<0.05). The TUG of group A was significantly shorter than that of group B at 5, 14, and 30 days (P<0.05). There was no significant difference in femoral offset or leg length on the X-ray films (t=1.273, P=0.851; t=0.409, P=0.327). The good rate of stem alignment was 82.86% (29/35) in group A, and was 85.30% (29/34) in group B, showing no significant difference (chi2=0.584, P=0.497). CONCLUSIONS: Both minimal invasive Supercap approach and conventional posterolateral approach are effective and safe for elderly displaced femoral neck fractures in hemiarthroplasty. Supercap approach has the advantages of less trauma, pain relief, and improvement of mobility and rapid rehabilitation. PMID- 29786383 TI - [TREATMENT OF ACETABULAR ANTERIOR AND POSTERIOR COLUMN FRACTURES BY MODIFIED Stoppa APPROACH]. AB - OBJECTIVE: To evaluate the surgical techniques, perioperative complications, clinical outcomes of the modified Stoppa approach in the treatment of acetabular anterior and posterior column fractures. METHODS: Between March 2008 and October 2014, 42 cases of acetabular anterior and posterior column fractures were treated by modified Stoppa approach or modified Stoppa approach combined with iliac fossa approach, and the clinical data were retrospectively analyzed. There were 20 females and 22 males with an average age of 43.2 years (range, 19-68 years). Fractures were caused by traffic accident in 21 cases, by falling from height in 16 cases, and by heavy pound in 5 cases. The time from injury to operation was 3 15 days (mean, 6 days). According to fracture classification of Letournel-Judet, there were 20 cases of both column fractures, 15 cases of anterior and posterior hemi-transverse fractures and 7 cases of T-shaped fractures. The intraoperative blood loss, the amount of blood transfusion, the operation time, the volumn of drainage, and complication were recorded. Matta radiological standard was used to evaluate the reduction quality of fracture, and Merled'Aubigne-Postel system to evaluate hip function. RESULTS: The average intraoperative blood loss was 900 mL; the average amount of blood transfusion was 400 mL; the average volume of drainage was 110 mL; and the average operation time was 165 minutes. Intraoperative complications included 4 cases of tractive injury of obturator nerve and 2 cases of the external iliac vein injury, and postoperative complications included 2 cases of lateral femoral cutaneous nerve palsies and 1 case of deep vein embolism of lower extremity, which were improved after treatment. The patients were followed up 36 months on average (range, 12-48 months). There was no infection or heterotopic ossification. According to Matta radiological evaluation system, the reduction quality of fractures was rated as excellent in 21 cases, good in 16 cases, and poor in 5 cases, with an excellent and good rate of 88.1%. The healing time of fracture was 3.5-8.0 months (mean, 5.1 months). According to Merled'Aubigne-Postel system for hip function, 20 cases were graded as excellent, 15 cases as good, 4 cases as fair, and 3 cases as poor, with an excellent and good rate of 83.3% at last follow-up. CONCLUSIONS: Modified Stoppa approach or with iliac fossa approach can get full exposure of quadrilateral area, good reduction, and firm internal fixation in the treatment of acetabular fractures associated with T-shaped fractures, both column fractures, anterior and posterior hemi-transverse fractures. PMID- 29786382 TI - [ISO-C3D NAVIGATION FOR PERCUTANEOUS SACROILIAC JOINT SCREW INTERNAL FIXATION FOR TREATMENT OF PELVIC POSTERIOR RING INJURIES]. AB - OBJECTIVE: To investigate the advantages and effectiveness of ISO-C3D guided percutaneous sacroiliac joint screw internal fixation for treatment of pelvic posterior ring injuries by comparing with anterior opened reduction and reconstruction plate internal fixation. METHODS: A retrospective analysis was made on the clinical data of 54 patients with posterior ring injury treated between June 2013 and January 2016. Of 54 patients, 33 underwent ISO-C3D guided percutaneous sacroiliac joint screws internal fixation (group A), and 21 underwent anterior opened reduction and reconstruction plate internal fixation (group B). There was no significant difference in gender, age, cause of injuries, injury to operation time, fractures type, combined injuries, and injury severity score (ISS) between 2 groups (P>0.05). The operation time, intraoperative blood loss, length of operative incision, hospitalization time, postoperative pain degree, reduction evaluation, and functional evaluation were compared between 2 groups. RESULTS: Group A was significantly better than group B in operation time, length of operative incision, and hospitalization time (P<0.05). The intraoperative blood loss of group A (10-20 mL) was significantly less than that of group B[(524.1+/-160.1) mL]. All patients of the 2 groups were followed up 7 to 24 months with an average of 11.6 months. No injury of vessel or nerve occurred in group A; worse neurological symptoms of lower limbs and incision infection were observed in 2 patients of group B respectively, and the other patients achieved primary healing of incision. At 48 hours after operation, the visual analogue scale (VAS) score of group A (1.7+/-0.7) was significantly lower than that of group B (8.2+/-0.8) (t=-30.463, P=0.000). Radiological examination showed fracture reduction. According to the Matta score standard, the reduction results were excellent in 21 cases (63.6%), good in 10 cases (30.3%), and fair in 2 cases (6.1%) in group A; the reduction results were excellent in 16 cases (76.2%), good in 4 cases (19.1%), and fair in 1 case (4.7%) in group B; and there was no significant difference between 2 groups (chi2=0.961, P=0.618). Fracture or dislocation healed well in 2 groups, and the walking function was restored. According to the Majeed standard for evaluation, the results were excellent in 23 cases (69.7%), good in 9 cases (27.3%), and fair in 1 case (3.0%) in group A; the results were excellent in 14 cases (66.7%), good in 5 cases (23.8%), and fair in 2 cases (9.5%) in group B; no significant difference was shown between 2 groups (chi2=1.501, P=0.591). CONCLUSIONS: Compared with anterior opened reduction and reconstruction plate internal fixation, ISO-C3D navigation percutaneous sacroiliac joint screw internal fixation is an ideal surgical method to treat pelvic posterior ring injury, with the characteristics of less trauma, less pain, precise screw implant and safety. PMID- 29786384 TI - [IMAGING ANALYSIS OF ACETABULAR CUP POSITIONS IN TOTAL HIP ARTHROPLASTY FOR ADULTS WITH ACETABULAR DYSPLASIA]. AB - OBJECTIVE: To investigate the influence of the degree of acetabular deformity and the learning-curve on the acetabular cup positions in total hip arthroplasty (THA) for adults with developmental dysplasia of hip (DDH). METHODS: Between January 2008 and December 2015, 130 patients (144 hips) with DDH underwent primary THA, and the clinical data were analyzed retrospectively. Fifty-three patients (59 hips) were admitted before 2012, and 77 patients (85 hips) were treated after 2012. There were 32 males and 98 females, aged from 31 to 83 years (mean, 61). Unilateral replacement was performed in 116 cases and bilateral replacement in 14 cases. Of 144 hips, 48 hips were rated as Crowe type I, 57 hips as type II, and 39 hips as type of III/IV. The standard pelvic radiograph was taken within 1 week after operation. The mediCAD software was adopted to measure the angle of anteversion and abduction, bony coverage, and the distance between true rotating center and optimal rotating center to the connection of teardrops and the horizontal distance between two centers to evaluate the qualified rate of acetabular cup positions. RESULTS: Compared with the patients with the same type in 2013-2015 group, the anteversion angle and qualified rate of acetabular cup position significantly decreased in patients with Crowe I (P<0.05); the horizontal distance significantly increased and qualified rate of acetabular cup position significantly decreased in patients with Crowe II (P<0.05); and the anteversion angle significantly decreased and the horizontal distance significantly increased in patients with Crowe III/IV (P<0.05) in 2008-2012 group. But no significant difference was shown in the other indexes (P>0.05). In all Crowe types, the vertical distance between the true rotating center and the optimal rotating center increased with the degree of acetabular deformity in both 2008-2012 group and 2013-2015 group, showing significant difference (P<0.05), but no significant difference was found in the other indexes (P>0.05). CONCLUSIONS: For adults with acetabular dysplasia, there are high potential risks for unsatisfactory acetabular cup positions during primary THA. So it is necessary to evaluate acetabular deformities and to sum up operative experience so as to improve the accuracy of cups installation. PMID- 29786385 TI - [BIOMECHANICAL STUDY ON LOCKED RECONSTRUCTION PLATE FOR INTERNAL FIXATION OF TRANSVERSE AND POSTERIOR WALL ACETABULAR FRACTURE]. AB - OBJECTIVE: To discuss the biomechanical stability of locked reconstruction plate for internal fixation of transverse and posterior wall acetabular fracture so as to provide a reliable basis for clinical application. METHODS: The models of transverse and posterior wall acetabular fracture were established in 16 anti corrosion acetabular specimens from 8 adult cadavers, which were randomly divided into experimental group and control group (n=8). Fracture was fixed with 10-hole posterior column locked reconstruction plate in the experimental group, and with 10-hole posterior column reconstruction plate combined with anterior column lag screw and posterior wall screws in the control group. Biomechanical testing machine was used for loading of 5/6 donor body mass the specimen in a speed of 15 N/s; the loading time was calculated and vertical loading.The longitudinal and quadrilateral body displacements of fracture were recorded to compare the biomechanical stability was performed. RESULTS: The quadrilateral body displacement of the experimental group[(1.99+/-0.32) mm] was greater than that of the control group[(1.75+/-0.22) mm], but there was no significant difference (t= 1.735, P=0.105). The longitudinal displacement[(1.56+/-049) mm] and the displacement of the posterior wall fracture block[(0.86+/-0.33) mm] in the experimental group were lower than those of the control group[(1.64+/-0.51) and (1.01+/-0.35) mm], showing no significant difference between 2 groups (t=0.293, P=0.772; t=1.516, P=0.154). CONCLUSIONS: For transverse and posterior wall acetabular fracture, application of locked reconstruction plate can provide sufficient biomechanical stability, reduce the risk of screw placement to acetabular joints. PMID- 29786389 TI - [TREATMENT OBSERVATION OF NASAL TIP DEFECTS RECONSTRUCTED BY BILOBED FLAPS AFTER GAINT NEVI EXCISION]. AB - OBJECTIVE: To discuss a reliable and aesthetic surgery method for the reconstruction of large defects on the top of nose after giant nevi resection. METHODS: Between January 2011 and June 2015, 46 cases of nasal tip defects caused by giant nevi resection were treated. Of 46 cases, 22 were male and 24 were female, aged 15-59 years (median, 28 years). The right ala nasi was involved in 28 cases, the apex nasi in 8 cases, and the left ala nasi in 10 cases. The diameters of nevi were from 8 to 12 mm (mean, 9.75 mm); no alar cartilage was invaded. Hair growth was seen in 14 cases. The duration of nasal nevi was from 3 years to 49 years (mean, 9.8 years). There were 9 recurrent patients who received laser therapy before surgery. The defects sizes after excision were from 10 mm*10 mm to 14 mm*14 mm. The bilobed flaps were used for one-stage reconstruction, which sizes were from 11 mm*10 mm to 15 mm*14 mm and from 10 mm*10 mm to 15 mm*14 mm. RESULTS: All the incisions healed by first intention, and the flaps survived. No complication of intracranial hemorrhage or subdural hemorrhage occurred. The patients were followed up 6 months to 5 years (mean, 18 months). The appearance of nasal tip and nasolabial fold was satisfactory, and no recurrence was found during follow-up. CONCLUSIONS: One-stage bilobed flap reconstruction for nasal tip defects after giant nevus resection is one of the effective, safe, and aesthetic surgery methods. PMID- 29786386 TI - [EFFECTIVENESS OF BILATERAL TOTAL HIP AND KNEE ARTHROPLASTY FOR SEVERE INFLAMMATORY ARTHROPATHIES]. AB - OBJECTIVE: To evaluate the application and effectiveness of bilateral total hip arthroplasty and total knee arthroplasty in the treatment of severe inflammatory arthropathies. METHODS: Between September 2008 and September 2015, 31 patients with severe inflammatory arthropathies were treated with bilateral total hip arthroplasty and total knee arthroplasty. Of 31 cases, 22 were male and 9 were female with an average age of 30 years (range, 20 to 41 years); there were 15 cases of rheumatoid arthritis and 16 cases of ankylosing spondylitis with an average onset age of 14 years (range, 5-28 years); all 4 ankylosed joints were observed in 11 cases, 3 ankylosed joints in 2 cases, 2 ankylosed joints in 6 cases, 1 ankylosed joint in 1 case, and no ankylosed joint in 11 cases. Before operation, the hip range of motion (ROM) value was (17.82+/-28.18) degrees , and the knee ROM value score was (26.45+/-30.18) degrees ; the hip Harris score was 29.64+/-11.58, and the hospital for special surgery (HSS) score was 27.07+/ 11.04. The patients were grouped and compared in accordance with etiology and ankylosed joint. RESULTS: One-stage arthroplasty was performed in 1 case, two stage arthroplasty in 22 cases, three-stage arthroplasty in 7 cases, and four stage arthroplasty in 1 case. The total operation time was 325-776 minutes; the total blood loss was 900-3 900 mL; the total transfusion volume was 2 220-8 070 mL; and the total hospitalization time was 21-65 days. The patients were followed up 12-94 months (mean, 51 months). The hip and knee ROM values, Harris score and HSS score at last follow-up were significantly improved when compared with preoperative ones (P<0.05). The subjective satisfaction degree was good in 16 cases, moderate in 10 cases, and poor in 5 cases. Periprosthetic infection occurred in 2 cases (3 knees), joint stiffness in 3 cases (6 knees), joint instability in 1 case (1 knee), leg length discrepancy of >2 cm in 2 cases, and flexion deformity of 10 degrees in 1 case (1 knee). The hip and knee ROM values, Harris score and HSS score showed no significant difference between patients with ankylosing spondylitis and patients rheumatoid arthritis at last follow-up (P>0.05). The hip and knee ROM values of the patients with ankylosed joint were significantly lower than those of patients with no ankylosed joint (P<0.05); the Harris score and HSS score of the patients with ankylosed joint were lower than those of patients with no ankylosed joint, but no significant difference was found (P>0.05). CONCLUSIONS: A combination of bilateral hip and knee arthroplasty is an efficient treatment for severe lower extremities deformity, arthralgia and poor quality of life caused by inflammatory arthropathies. However, the postoperative periprosthetic infection and stiffness of knee are important complications influencing the effectiveness of operation. PMID- 29786388 TI - [EFFECTIVENESS OF V-Y ADVANCED RETROAURICULAR FLAP FOR REPAIRING MILD AND MODERATE EARLOBE DEFECTS]. AB - OBJECTIVE: To investigate the effectiveness of the V-Y advanced retroauricular flap for repairing mild and moderate earlobe defect. METHODS: Between September 2014 and July 2015, V-Y advanced retroauricular flap was used to repair earlobe defect in 6 patients. There were 1 male and 5 females, aged 18 to 30 years (mean, 23 years). The left earlobe was involved in 2 cases and the right earlobe in 4 cases, including 2 cases of congenital earlobe defect and 4 cases of secondary earlobe defect; 1 patient had congenital deformity of upper auricle. According to self-made criteria for earlobe defect, 5 cases were rated as mild defect and 1 case as moderate defect. RESULTS: All incisions healed at the first stage, and the flaps survived smoothly. The patients were followed up 3 to 12 months, with an average of 9 months. The reconstructed earlobes had natural size and shape, and smooth curve; the texture and color were close to the adjacent skin. The effectiveness was satisfactory. CONCLUSIONS: The V-Y advanced retroauricular flap for repairing mild and moderate earlobe defect can achieve natural earlobe and aesthetic plastic effectiveness, so it is a safe and ideal earlobe reconstruction method. PMID- 29786391 TI - [REPAIR OF PALM SOFT TISSUE DEFECT WITH MEDIAL TARSAL COMBINED WITH MEDIAL PLANTAR FLAP PEDICLED WITH FREE DORSALIS PEDIS ARTERY]. AB - OBJECTIVE: To investigate the effectiveness of medial tarsal combined with medial plantar flap pedicled with free dorsalis pedis artery in the repair of palm soft tissue defect. METHODS: Between September 2013 and December 2015, 9 cases of palm soft tissue defects were repaired with medial tarsal combined with medial plantar flap pedicled with free dorsalis pedis artery. There were 7 males and 2 females with a mean age of 33 years (range, 21-52 years). The causes included traffic accident injury in 4 cases, crushing injury by heavy object in 3 cases, and electrical injury in 2 cases. The time between injury and admission was 3 hours to 2 days (mean, 9 hours). Five cases had pure soft tissue; combined injuries included tendon exposure in 2 cases, median nerve defect in 1 case, and exposure of tendon and nerve in 1 case. After debridement, the soft tissue defect area ranged from 6 cm*4 cm to 11 cm*6 cm. The flap size ranged from 7.0 cm*4.5 cm to 13.0 cm*7.0 cm. The vascular pedicle length was from 6 to 10 cm (mean, 7.5 cm). The donor sites were covered with ilioinguinal full thickness skin graft. RESULTS: Nine flaps survived, primary healing of wound was obtained. Partial necrosis occurred at the donor site in 1 case, and the other skin graft successfully survived. All patients were followed up 6-20 months (mean, 10 months). All flaps had soft texture and satisfactory appearance; the cutaneous sensory recovery time was 4-7 months after operation (mean, 5 months). At last follow-up, sensation recovered to grade S4 in 4 cases, to grade S3+ in 3 cases, and to grade S3 in 2 cases; two-point discrimination was 7-10 mm (mean, 8.5 mm). According to Society of Hand Surgery standard for the evaluation of upper part of the function, the hand function was excellent in 5 cases, good in 3 cases, and fair in 1 case. The donor foot had normal function. CONCLUSIONS: The medial tarsal combined with medial plantar flap pedicled with free dorsalis pedis artery can repair soft tissue defect of the palm, and it has many advantages of soft texture, satisfactory function, and small injury at donor site. PMID- 29786390 TI - [EFFECTIVENESS OF MODIFIED Zitelli BILOBED FLAPS FOR REPAIRING SOFT TISSUE DEFECT OF LOWER ONE-THIRD NOSE]. AB - OBJECTIVE: To investigate the clinical application of the modified Zitelli bilobed flaps in repairing soft tissue defect of lower one-third nose. METHODS: Between February 2009 and February 2014, 26 patients with soft tissue defect of lower one-third nose after resection of basal cell carcinoma underwent reconstruction using modified Zitelli bilobed flaps. There were 15 males and 11 females, aged 48-65 years (mean, 56 years). Tumor involved the skin layer in all patients. According to TNM staging, 19 cases were rated as TisN0M0 and 7 cases as T1N0M0. The disease duration was 1-5 years (mean, 3 years). The mass size ranged from 1.0 cm*0.5 cm to 1.5 cm*1.0 cm. The defect size ranged from 1.5 cm*1.0 cm to 2.0 cm*1.5 cm after resection of basal cell carcinoma. The modified ipsilateral Zitelli bilobde flaps were designed and harvested for one-stage repair of defect, and the double-leaf flap size ranged from 2.5 cm*2.0 cm to 3.0 cm*2.5 cm and 1.5 cm*1.0 cm to 2.0 cm*1.5 cm. The donor site defects were sultured directly. RESULTS: Twenty-six flaps survived and incision healed primarily. No postoperative complications of hematoma, infection, and necrosis of skin flap occurred. No stretching deformation of local organs, the shape of the nose and face was symmetric. Twenty-six patients were followed up 3-24 months (mean, 13 months). Nasal and facial appearance was good and had no obvious scar formation, and patients were satisfied with the appearance. There was no tumor recurrence during follow-up. CONCLUSIONS: The modified Zitelli bilobed flap to repair soft tissue defect of lower one-third nose (the defect diameter within 2.0 cm) can obtain satisfactory effectiveness in appearance. PMID- 29786387 TI - [PROXIMAL FIBULAR OSTEOTOMY COMBINED WITH ARTHROSCOPIC DEBRIDEMENT FOR TREATING MEDIAL KNEE OSTEOARTHRITIS WITH VARUS]. AB - OBJECTIVE: To evaluate the effectiveness of proximal fibular osteotomy combined with arthroscopic debridement in the treatment of medial knee osteoarthritis with varus. METHODS: Between December 2013 and June 2015, 61 patients with medial knee osteoarthritis with varus were treated by arthroscopic debridment in 32 cases (group A) and by proximal fibular osteotomy combined with arthroscopic debridement in 29 cases (group B). No significant difference was found in gender, age, side, disease duration, OA stage, visual analogue scale (VAS) score, and knee society score (KSS) between 2 groups (P>0.05). The clinical outcome was evaluated by VAS score and KSS score at 1 week, 3 months, and 12 months after operation. RESULTS: The patients in 2 groups were followed up 12 months. All incisions healed by first intention. There was no significant difference in complication incidence between groups A and B (0 vs. 3.4%; chi2=0.723, P=0.432). The VAS scores were significantly decreased at 1 week, 3 months, and 12 months after operation when compared with preoperative score in 2 groups (P<0.05). The VAS score of group A was significantly lower than that of group B at 1 week after operation (P<0.05), but the VAS score of group A was significantly higher than that of group B at 3 months, and 12 months after operation (P<0.05). The knee function was obviously improved in 2 groups, and the KSS scores at 1 week, 3 months and 12 months after operation were significantly better than preoperative score (P<0.05). The KSS score of group A was significantly lower than that of group B at 3 months, and 12 months after operation (P<0.05). CONCLUSIONS: Proximal fibular osteotomy combined with arthroscopic debridement can treat knee malalignment and disease in knee, it is an effective and safe method to treat the medial knee osteoarthritis with varus. PMID- 29786392 TI - [RECONSTRUCTION OF DEGLOVED THUMBS WITH FREE SECOND TOE DORSAL FLAP COMBINED WITH MIDDLE OR RING FINGER ISLAND FLAP]. AB - OBJECTIVE: To investigate the effectiveness of free second toe dorsal flap combined with middle or ring finger island flap for repairing degloved thumbs. METHODS: Between August 2009 and June 2013, 6 patients with degloving injury of the thumb were treated using free second toe dorsal flap combined with middle or ring finger island flap. There were 4 males and 2 females, aged 19-44 years (mean, 32 years). The left thumb was involved in 2 cases and the right thumb in 4 cases, including 5 cases of type II and 1 case of type III degloving injury. The size of wound was 5.5 cm*2.5 cm to 6.5 cm*5.0 cm. After emergency debridemented, 5 patients underwent vacuum sealing drainage and surgical repair after 3-5 days; 1 patient underwent abdominal embedding and repair after 14 days. The size of second toe dorsal flap ranged from 2.5 cm*2.2 cm to 4.2 cm*3.0 cm, and the size of middle or ring finger island flap ranged from 2.0 cm*1.5 cm to 3.5 cm*2.8 cm. Neurorrhaphy was performed between the plantar digital nerve of the second toe and the proper digital nerve at the recipient site in 5 cases, and no nerve anastomose in 1 case. All the distal phalanxes were partially excised. The donor sites were covered with free skin grafts. RESULTS: All of the flaps survived completely and incision healed by first intention. Three patients had alloesthesia of the middle or ring finger island flaps. All of the 6 patients were followed up from 6 months to 3 years (mean, 23 months). The flaps had good color and soft texture, and the finger had satisfactory appearance, but the fingernails were smaller than that of normal side. The sensation of the dorsum of the second toe reached S3, and the mean two-point discrimination of the pulp was 6 mm (range, 4-7 mm). According to total active movement (TAM) system, the function of the thumbs was excellent in 5 cases and good in 1 case. CONCLUSIONS: A combination of free second toe dorsal flap and middle or ring finger island flap is a useful and reliable technique for reconstruction of a degloved thumb. PMID- 29786393 TI - [PREPUTIAL PEDICLED FLAP PHALLOPLASTY FOR REPAIR OF SEVERE WEBBED PENIS]. AB - OBJECTIVE: To evaluate the effectiveness of preputial pedicled flap phalloplasty for repair of severe webbed penis. METHODS: Between May 2011 and May 2015, 23 boys with severe webbed penis were treated. The age ranged from 2 years and 8 months to 8 years and 3 months (mean, 4 years and 8 months). According to El Koutby & El Gohary classification, 14 cases were rated as grade 3 simple webbed penis and 9 cases as compound webbed penis (2 cases of type 1, 2 cases of type 2, and 5 cases of type 3). The penis length was 2.1-5.4 cm (mean, 3.4 cm), and the penoscrotal angle was 130-160 degrees (mean, 144 degrees ). All the glans could not be exposed. No other urinary system diseases and no history of penile surgery were found in children. All cases underwent one stage preputial pedicled flap phalloplasty. RESULTS: After successful correction, the penis length was 3.6-6.4 cm (mean, 4.7 cm); the penoscrotal angle was 90-110 degrees (mean, 97 degrees ). Clear skin boundaries were observed at penile and scrotal parts. No web skin or scrotal skin was left on the penis. Primary healing of incision was obtained, with no necrosis of the flap or infection. All cases were followed up 12 to 41 months (mean, 25 months). No penile curvature, abnormal sensation of glans, or recurrence of the penoscrotal angle occurred, and the patients had normal urination. CONCLUSIONS: Preputial pedicled flap phalloplasty can be used as one stage repair for severe webbed penis. The penis is close to natural state and had satisfactory appearance, avoiding the possibility of long-term edema and penile curvature. PMID- 29786394 TI - [SURAL NUEROFASCIOCUTANEOUS FLAP WITH SLOPE-DESIGNED SKIN ISLAND FOR COVERAGE OF SOFT TISSUE DEFECTS LONGITUDINAL IN DISTAL PRETIBIAL REGION OR TRANSVERSE IN HEEL AND ANKLE]. AB - OBJECTIVE: To introduce a modified technique of a sloped skin island design for the distally based sural nuerofasciocutaneous flap to reconstruct soft tissue defects longitudinal in distal pretibial region or transverse in the heel and ankle, and report the effectiveness of the modified technique. METHODS: Between April 2001 and January 2016, 37 patients (38 defects) with longitudinal defects in distal pretibial region or transverse defects in the heel and ankle were treated with the sural nuerofasciocutaneous flap with slope-designed skin island. These patients included 28 males and 9 females, with a median age of 37 years (range, 5-78 years). The horizontal and vertical dimensions ranged from 3 to 8 cm and 8.5 to 14.5 cm in 11 distal pretibial defects, and from 9 to 21 cm and 3.0 to 10.5 cm in 27 heel and ankle defects, respectively. The disease duration ranged from 2 days to 5 years. RESULTS: When the skin islands were routinely designed, the skin islands of 25 flaps would exceed the lateral limit (the anterior border of the fibula) laterally or medial limit (the medial border of the tibia) medially. After the skin islands were obliquely designed, the horizontal dimensions in 38 flaps decreased an average of 5.4 cm (range, 2.5 to 14.8 cm), and the vertical dimensions increased an average of 5.3 cm (range, 2 to 15 cm). The rotation angles ranged from 42 degrees to 90 degrees , with an average of 67 degrees . Thirty-five flaps survived uneventfully. Margin necrosis occurred in 2 flaps, and partial necrosis in 1 (2.6%) flap. The grafted skins at donor site survived, and primary healing of incision was obtained. All patients were followed up 6 to 42 months (mean, 10 months). No infection or ulceration was noted during the follow-up period, and the appearances of the flaps were satisfactory. At last follow-up, according to Boyden et al criteria, the limb function was excellent in 30 cases, good in 6 cases, and poor in 2 cases, with the excellent and good rateof 94.7%. CONCLUSIONS: When the distal sural nuerofasciocutaneous flap is used to reconstruct soft tissue defects longitudinal in distal pretibial region or transverse in the heel and ankle, the modified technique of sloped skin island design can decrease the horizontal dimension of the skin island, improve the flap survival rate, and extend its indications. PMID- 29786395 TI - [REPAIR OF ANKLE SKIN AND SOFT TISSUE DEFECT WITH FREE SUPERFICIAL ILIAC CIRCUMFLEX ARTERY PERFORATOR FLAP]. AB - OBJECTIVE: To investigate the effectiveness of free superficial iliac circumflex artery perforator flap for repair of foot skin and soft tissue defect. METHODS: Between January 2010 and December 2015, 16 patients with ankle skin and soft tissue defect were treated. There were 13 males and 3 females with an average age of 32 years (range, 5-56 years). The causes included traffic accident injury in 8 cases, machinery injury in 3 cases, falling injury in 3 cases, and electrically injury in 2 cases. The time from injury to hospital was 1 to 6 hours (mean, 3.5 hours). The wound sites included foot dorsum skin defect in 6 cases, ankle skin defect in 5 cases, the back foot and ankle skin defect in 5 cases. The skin defect size ranged 5 cm*4 cm to 16 cm*7 cm. All patients had tendon exposure, and 8 patients had fracture. An emergency repair was performed in 6 cases, and selective surgery in 10 cases. The free iliac circumflex artery perforators flap was used to repair defect; the flap size was 6 cm*5 cm to 17 cm*8 cm, and the flap thickness was 0.4 to 1.1 cm (mean, 0.8 cm). RESULTS: The flaps survived in the other 15 patients with primary healing of wounds except 1 patient because the iliac circumflex artery was too small to provide good blood supply, who underwent repair with local skin flap. Incision at donor site healed by first intention. The 15 cases were followed up 6-24 months (mean, 13 months). The appearance of the foot was satisfactory, and the flap had good texture without bulky flaps. CONCLUSIONS: Free iliac circumflex artery perforators flap is one of ideal flaps in repair of skin defect of the foot and ankle because of hidden donor site, reliable blood supply, less injury to donor site, and full use of the flap. PMID- 29786396 TI - [ILIAC FLAP COMBINED WITH ANTEROLATERAL THIGH FLAP FOR REPAIR OF FIRST METATARSAL BONE AND LARGE SKIN DEFECT]. AB - OBJECTIVE: To investigate the surgical methods and effectiveness to use the iliac flap combined with anterolateral thigh flap for repair of the first metatarsal bone and large skin defect. METHODS: Between January 2013 and January 2016, iliac flap combined with anterolateral thigh flap was used to repair the first metatarsal bone and large skin defect in 9 patients. There were 5 males and 4 females, with a median age of 15 years (range, 10 to 60 years). The causes included traffic accident injury in 6 cases and crush injury of machine in 3 cases. The average time from injury to operation was 3 hours to 14 days (mean, 7 days). The size of skin soft tissue defect ranged from 10 cm*6 cm to 20 cm*10 cm. The size of first metatarsal bone defect ranged from 2 cm*1 cm to 5 cm*1 cm. The size of iliac flap was 3.0 cm*1.5 cm to 6.0 cm*1.5 cm, and the size of anterolateral thigh flap was 10 cm*6 cm to 20 cm*10 cm. The donor site was directly sutured or repaired by free skin graft. RESULTS: After operation, the composite flaps survived with primary healing of wound; the skin grafts at donor site survived and the incision healed by first intention. All patients were followed up 6 months to 2 years (mean, 1.6 years). X-ray examination showed that the bone healing time was 3.5-5.0 months (mean, 4 months). The flap had soft texture, good color and appearance. All patients could normally walk. According to the American Orthopaedic Foot and Ankle Society (AOFAS) standard, the foot function was excellent in 6 cases and good in 3 cases, and the excellent and good rate was 100% at last follow-up. CONCLUSIONS: The iliac flap combined with anterolateral thigh flap for repair of the first metatarsal bone and large skin defect is a practical way with good shape at one stage. PMID- 29786397 TI - [POSTERIOR ATLANTOAXIAL LATERAL MASS SCREW FIXATION AND SUBOCCIPITAL DECOMPRESSION FOR TREATMENT OF Arnold-Chiari MALFORMATION ASSOCIATED WITH ATLANTOAXIAL DISLOCATION]. AB - OBJECTIVE: To evaluate the effectiveness of the posterior atlantoaxial lateral mass screw fixation and suboccipital decompression in the treatment of Arnold Chiari malformation associated with atlantoaxial joint dislocation. METHODS: Between September 2012 and November 2015, 17 cases of Arnold-Chiari malformation associated with atlantoaxial dislocation were treated by the posterior atlantoaxial lateral mass screw fixation and suboccipital decompression and expansion to repair the dura mater and bone graft fusion. There were 10 males and 7 females, aged 35-65 years (mean, 51.4 years). The disease duration was 14 months to 15 years with an average of 7.4 years. According to Arnold-Chiari malformation classification, 13 cases were rated as type I, 3 cases as type II, and 1 case as type III-IV. Cervical nerve root stimulation and compression symptoms were observed in 12 cases, occipital foramen syndrome in 11 cases, cerebellar compression symptoms in 6 cases, and syringomyelia in 10 cases. RESULTS: Primary healing of incision was obtained in the other patients except 1 patient who had postoperative cerebrospinal fluid leakage after removal of drainage tube at 3 days after operation, which was cured after 7 days. All patients were followed up 6 months to 2 years, with an average of 18.4 months. The neurological dysfunction was improved in different degrees after operation. The Japanese Orthopedic Association (JOA) score was significantly increased to 16.12+/-1.11 at 6 months from preoperative 11.76+/-2.01 (t=13.596, P=0.000); compression of spinal cord and medulla was improved. X-ray examination showed bone graft fusion at 6 months after operation. In 10 patients with spinal cord cavity, MRI showed empty disappearance in 3 cases, empty cavity lessening in 6 cases, and no obvious change in 1 case at 6 months. CONCLUSIONS: Atlantoaxial lateral mass screw fixation and suboccipital decompression and expansion to repair the dura mater can obtain good effectiveness in the treatment of Arnold Chiari malformation associated with atlantoaxial transarticular dislocation. PMID- 29786398 TI - [EFFECTIVENESS AND SAFETY OF SIMPLY ANTERIOR APPROACH FOR LOWER CERVICAL SPINE FRACTURE DISLOCATION (Allen-Ferguson II OR III TYPE) WITHOUT SPINAL CORD INJURY]. AB - OBJECTIVE: To study the effectiveness and safety of simply anterior approach for lower cervical spine fracture dislocation (Allen-Ferguson II or III type) without spinal cord injury. METHODS: Twenty-five patients with lower cervical spine fracture dislocation (Allen-Ferguson II or III type) without spinal cord injury were treated between June 2013 and June 2015. There were 17 males and 8 females with an average age of 41.2 years (range, 31-57 years). Injury was caused by falling from height in 11 cases, by bruise in 5 cases, by crash of heavy object in 6 cases, and by traffic accident in 3 cases. There were 24 cases of fresh fractures and 1 case of old fracture. According to the Frankel grading criteria, 19 cases were rated as grade E and 6 cases as grade D. The injured levels included C4, 5 in 5 cases, C5, 6 in 14 cases, and C6, 7 in 6 cases. Unilateral locked-facet joint was observed in 9 cases, and bilateral locked-facet joint in 16 cases. The operation time, intraoperative blood loss, and surgical complications were recorded; the Odom standard was used to evaluate the effectiveness. The Cobb angle and D-value (the degree of cervical kyphosis or lordosis) were measured on the X-ray film, the bone graft fusion rate was recorded. RESULTS: The operation was successfully completed in 25 patients; the operation time was 66 to 115 minutes, the intraoperative blood loss was 80 to 220 mL. The postoperative follow-up time was 12 to 36 months (mean, 19.3 months). Postoperative temporary dysphagia occurred in 1 case, and pain at donor site in 2 cases; there were no complications of spinal cord injury, hematoma, hoarse, and esophageal fistula. The nerve function was improved from preoperative grade D to postoperative grade E at 3 months. The X-ray films showed bone graft fusion; there was no loss of intervertebral height or loosening of internal fixation. At 3 months after operation, the effectiveness was excellent in 18 cases, good in 6 cases, and fair in 1 case, and the excellent and good rate was 96.0%. The postoperative Cobb angle and the D value were significantly improved when compared with preoperative ones (P<0.05). CONCLUSIONS: Simple anterior approach has the advantages of good effectiveness, small trauma, and fast recovery for treating lower cervical spine fracture dislocation (Allen-Ferguson II or III type) without spinal cord injury. PMID- 29786399 TI - [IMAGING STUDY ON LUMBAR PLEXUS BY MINIMALLY INVASIVE LATERAL TRANSPSOAS APPROACH]. AB - OBJECTIVE: To analyze the relative position between lumbar plexus and access corridor of minimally invasive lateral transpsoas approach based on magnetic resonance imaging distribution of lumbar plexus by three dimensional reconstruction technique, so as to evaluate approach safety. METHODS: Three dimensional fast imaging employing steady-state acquisition sequences of lumbar spine were performed on 71 patients with lumbar degenerative diseases between July 2012 and January 2015. The axial image distance between the anterior edge of lumbar plexus and sagittal central perpendicular line (SCPL) of disc was determined using the distance formula at the mid-disc space from L1, 2 to L4, 5 level. SCPL was drawn perpendicularly to the sagittal plane of intervertebral disc and it passed through its central point, which is initial dilator trajectory for transpsoas approach. With respect to the SCPL of disc, the distance with a positive value indicated neural tissue posterior to it whereas anterior to it represented by a negative value. RESULTS: Various branches of lumbar plexus which passed through the psoas major anterior to the SCPL of disc were identified in 42 (59.2%), 58 (81.7%), and 70 (98.6%) patients at L2, 3, L3, 4, and L4, 5 levels, respectively. It is possible to infer the presence of genitofemoral nerve in accordance with relevant anatomic research. A ventral migration of intrapsoas nerves is identified from L1, 2 to L4, 5 level. All differences between levels were statistically significant (P<0.05). CONCLUSIONS: With respect to the SCPL of disc, a pass way of guide wire or a radiographic reference landmark to place working channel, lumbar plexus lie posterior to it from L1, 2 to L3, 4 level and shift anteriorly to it at L4, 5 level, while genitofemoral nerve locate anterior to the SCPL from L2, 3 to L4, 5 level. Neural retraction may take place during sequential dilation of working channel especially at L4, 5 level. PMID- 29786400 TI - [HYBRID REPAIR OF PARASTOMAL HERNIA WITH DynaMesh-IPST]. AB - OBJECTIVE: To investigate the technique and early results of hybrid repair of parastomal hernia with the DynaMesh-IPST. METHODS: A retrospective analysis was made on the clinical data of 28 patients who underwent DynaMesh-IPST hybrid repair of parastomal hernia between October 2013 and June 2016. There were 18 males and 10 females, aged 49-84 years (mean, 71 years). The disease duration of parastomal hernia was 6-60 months (mean, 27.6 months). The body mass index (BMI) was 17-35 (mean, 25.6); there were 15 obese patients (BMI>26). RESULTS: The operation was completed smoothly in all patients. The mean stoma diameter was 6 cm (range, 4-9 cm). The mean operation time was 142 minutes (range, 110-190 minutes). The mean hospital stay was 9 days (range, 7-12 days). Seroma was found in 2 patients, and was cured by needle aspiration and pressure bandage. All 28 cases were followed up 1-33 months (mean, 19 months). No recurrence, infection, intestinal fistula, and stoma-related problems were found. The appearance of abdominal wall was symmetrical. CONCLUSIONS: DynaMesh-IPST hybrid repair is a safe and feasible method for parastomal hernia, and the short-term operative result is satisfactory. PMID- 29786401 TI - [EFFECTIVENESS EVALUATION OF FACIAL METICULOUS FAT GRAFTING BY FAT GRANULES INJECTION ASISTOR]. AB - OBJECTIVE: To study the effectiveness of facial meticulous fat grafting by fat granules injection asistor. METHODS: Between January and August 2015, 46 patients received facial autologous fat grafting for rejuvenation. There were 7 males and 39 females, aged 21-65 years (mean, 34 years). Firstly, the faces were divided into 10 cosmetic zonations according to facial aesthetic criteria, then autologous fat grafting was carried out by fat granules injection asistor. The autologous fat was filled into 1, 2, 3, 4, 5, 6, 7, 8, and 9 cosmetic zonations in 3, 7, 5, 3, 8, 4, 2, 10, and 4 cases respectively; the injected fat amount was 2-110 mL (mean, 47 mL). RESULTS: The swelling period was from 5 to 15 days after operation (mean, 7 days), and there were no complications of infection, cyst, introvascular thrombogenesis, and so on. They were followed up 1-7 months (mean, 3 months). The effect of face rejuvenation was satisfactory. CONCLUSIONS: Cosmetic zonation of face is helpful for preoperative evaluation of autologous fat grafting, and the fat granules injection asistor is beneficial to reach better effect of face rejuvenation. PMID- 29786403 TI - [RESEARCH PROGRESS OF MicroRNA IN OSTEOARTHRITIS CARTILAGE MATRIX DEGRADATION]. AB - OBJECTIVE: To summarize the research progress of microRNA (miRNA) in the osteoarthritis (OA) cartilage matrix degradation. METHODS: The domestic and foreign related literature about the miRNA in the OA cartilage matrix degradation was reviewed, summarized, and analyzed. RESULTS: OA is a common chronic joint disease characterized by cartilage degeneration, its etiology and pathogenesis are still not completely clear. miRNA, a kind of small single stranded non-coding RNA molecule, is closely correlated with inflammatory mediators and various cytokines during the cartilage matrix degradation, suggesting that miRNAs have important regulatory functions at the molecule and cellular levels. CONCLUSIONS: miRNA can serve as potential biomarkers and will give new insight into diagnosis and therapeutic strategies in OA. PMID- 29786402 TI - [PREPARATION OF PERSONALIZED BRAIN CAVITY SCAFFOLD WITH THREE-DIMENSIONAL PRINTING TECHNOLOGY BASED ON MAGNETIC RESONANCE IMAGING]. AB - OBJECTIVE: To explore a method of three-dimensional (3D) printing technology for preparation of personalized rat brain tissue cavity scaffolds so as to lay the foundation for the repair of traumatic brain injury (TBI) with tissue engineered customized cavity scaffolds. METHODS: Five male Sprague Dawley rats[weighing (300+/-10) g] were induced to TBI models by electric controlled cortical impactor. Mimics software was used to reconstruct the surface profile of the damaged cavity based on the MRI data, computer aided design to construct the internal structure. Then collagen-chitosan composite was prepared for 3D bioprinter of bionic brain cavity scaffold. RESULTS: MRI scans showed the changes of brain tissue injury in the injured side, and the position of the cavity was limited to the right side of the rat brain cortex. The 3D model of personalized cavity containing the internal structure was successfully constructed, and cavity scaffolds were prepared by 3D printing technology. The external contour of cavity scaffolds was similar to that of the injured zone in the rat TBI; the inner positive crossing structure arranged in order, and the pore connectivity was good. CONCLUSIONS: Combined with 3D reconstruction based on MRI data, the appearance of cavity scaffolds by 3D printing technology is similar to that of injured cavity of rat brain tissue, and internal positive cross structure can simulate the topological structure of the extracellular matrix, and printing materials are collagen-chitosan complexes having good biocompatibility, so it will provide a new method for customized cavity scaffolds to repair brain tissue cavity after TBI. PMID- 29786404 TI - [NEW PROGRESS OF ACELLULAR FISH SKIN AS NOVEL TISSUE ENGINEERED SCAFFOLD]. AB - OBJECTIVE: To review the recent research progress of acellular fish skin as a tissue engineered scaffold, and to analyze the feasibility and risk management in clinical application. METHODS: The research and development, application status of acellular fish skin as a tissue engineered scaffold were comprehensively analyzed, and then several key points were put forward. RESULTS: Acellular fish skin has a huge potential in clinical practice as novel acellular extracellular matrix, but there have been no related research reports up to now in China. As an emerging point of translational medicine, investigation of acellular fish skin is mainly focused on artificial skin, surgical patch, and wound dressings. CONCLUSIONS: Development of acellular fish skin-based new products is concerned to be clinical feasible and necessary, but a lot of applied basic researches should be carried out. PMID- 29786405 TI - Surgical versus endovascular revascularization of subclavian artery arteriosclerotic disease. AB - BACKGROUND: Endovascular treatment offers an alternative less-invasive approach to open repair for subclavian artery atherosclerotic disease (SAAD). However, only few studies compared the outcomes of both strategies in the long run. This study reports on the performance of endovascular and surgical revascularization for SAAD. METHODS: A retrospective review was conducted on patients treated for SAAD at two institutions between January 1998 and December 2015. Primary outcome of this study was the composite endpoint of re-intervention-free survival (RFS) defined as time to re-intervention and/or death from any cause. Secondary endpoints included primary patency- (PPR) and secondary patency (SPR) rates as well as overall survival and time to re-intervention. RESULTS: Surgical treatment was the preferred treatment option in 27 (25%) patients, while 83 (75%) patients underwent primary stent therapy. The median follow up amounted to 87 months (interquartile range (IQR) 38 to 151) in the surgical group and 27 (IQR, 12 to 59) in the endovascular (p=0.0001). Severe arterial wall calcification was more commonly observed in the surgical arm (p<0.0001), while mild and moderate calcification in the endovasculari (P=.0004 and P=.014). Vessel occlusion was more frequent among patients treated surgically (100% vs 34%, p<0.0001). At 98 months RFS was significantly higher after surgical treatment (95% vs 54%, HR:8.4, 95%CI: 3,9 to 18,1, p=0.0002). Although overall survival did not differ significantly between the two groups (HR: 4.28, 95%CI: 0.86 to 21.22, p= 0.093), open repair was associated with reduced re-intervention rate (HR: 12.04, 95%CI: 4.98 to 29.12, p=0.001). The PPR at 98 months following surgical and endovascular therapy amounted to 96% and 65% (HR: 12.87, 95%CI: 5.44 to 30.44, p=0.0008) respectively. No significant difference was observed regarding the SPR between the two groups (100% vs 95%, p= 0.090). CONCLUSIONS: Surgical treatment was associated in this cohort with increased patency and a significant reduction of re-interventions compared to the endovascular approach. PMID- 29786407 TI - Even redo ascending aorta replacement has low mortality in elective setting. PMID- 29786406 TI - Mitroflow LXA structural deterioration following aortic valve replacement: a single-center experience. AB - BACKGROUND: Concerns have been previously raised regarding the potential early degeneration of the Mitroflow (Sorin Group Italia, Saluggia, Vercelli, Italy) bioprostheses. We aimed to evaluate our clinical experience with the Mitroflow LXA prosthesis for aortic valve replacement. METHODS: We prospectively analyzed data from 227 consecutive patients (133 males, mean age 73.9+/-9.2 years) implanted with the Mitroflow LXA between February 2007 and October 2011. Follow up data were obtained by contacting the referring cardiologists. Kaplan-Meier curves were constructed for all-cause mortality, valve related mortality and structural valve degeneration (SVD). Multivariable analysis was conducted to identify SVD predictors. RESULTS: Median follow-up time was 54.2+/-37.9 months and completeness of follow-up was 95%. Overall mortality in the entire series was at 31% (N.=71) and mortality from cardiac or unknown causes at 20% (N.=46). SVD occurred in 24 patients (10%) (median delay between implantation and diagnosis: 62.6 (36.5) months). Reintervention was required in 20 cases (13 redo surgery, 7 percutaneous transcatheter valve intervention). The 8 years actuarial global survival was 54.7+/-4.9%, freedom from valve related mortality 67.5+/-4.9% and freedom from SVD 72+/-8%. The estimated freedom from SVD was significantly (P=0.007) longer in larger prosthesis (diameter >21 mm, 77+/-11%) compared to the smaller devices (<=21 mm, 59+/-13%.). Multivariate analysis identified smaller prostheses and age at implantation as independent predictors of SVD. CONCLUSIONS: The Mitroflow LXA showed evidence of early SVD in this cohort. A close follow-up of these patients is strongly advised. PMID- 29786408 TI - Impact of additional tricuspid valve annuloplasty in TOF patients undergoing pulmonary valve replacement. AB - BACKGROUND: Many patients with tetralogy of Fallot (TOF) who underwent surgical correction of their congenital cardiac malformation during infancy develop right ventricular dysfunction and exercise intolerance in the long term. The right ventricle (RV) dilates due to the development of severe pulmonary regurgitation (and secondary tricuspid insufficiency). To reduce RV dilation and improve exercise tolerance pulmonary valve replacement (PVR) is the common therapeutic strategy. Whether concomitant tricuspid valve repair (TVR) is beneficial in these pure volume-overload conditions is still unknown. METHODS: 28 adults who received surgical PVR were included in the study and perioperative data including operative records, postoperative course and echocardiography before and after surgery was analyzed retrospectively. RESULTS: Mean age of the patients was 41.1 13.5 years and PVR with Carpentier Edwards Perimount bioprostheses was performed 32.0 9.5 years after initial cardiac surgery. Preoperative echocardiography revealed moderate RV dilation in 60.7% of the patients and severe pulmonary valve regurgitation in 82.3%. Ten patients underwent additional TVR. Indication was purely based on annular dilation (> 40mm), independent from the degree of tricuspid insufficiency. Periprocedural data of both groups did not differ significantly. However, ICU stay was significantly increased in patients who underwent additional TVR (p=0.0420) and these patients developed more complications (p=0.0407) while postoperative echography showed the same recovery of the RV function and diameters, independent of concomitant TVR. CONCLUSIONS: In grown-ups with congenital heart disease surgical PVR +/- TVR is a safe procedure with good short-term outcomes. As the RV remodels after volume reduction, indication for concomitant TVR should be restrictive. PMID- 29786409 TI - Vascular access for haemodialysis: is the outcome improvement still possible? PMID- 29786411 TI - BAD transmission and SAD distribution: a new scenario for critical limb ischemia. AB - BACKGROUND: Most of the studies on peripheral artery disease (PAD) focused on above-the-ankle artery disease, while less is known about foot artery disease. We hypothesize a scenario were two different diseases can be present in PAD patients, big artery disease (BAD) and small artery disease (SAD), overlapping at the foot level; the aim of this study is to evaluate their prevalence and their correlation with risk factors and critical limb ischemia (CLI) in a large cohort of patients with symptomatic PAD. METHODS: We retrospectively reviewed 1915 limbs of 1613 patients (502 females, mean age 72.4+/-10.8 years) who underwent angiography between September 2009 and November 2013. Age, sex, diabetes, smoke history, high blood pressure, dialysis and BMI were considered as risk factors. Logistic regression was performed to test the association of arterial lesions patterns and CLI, and to evaluate the association between risk factors and lesion localization. RESULTS: SAD was present in 414 patients (25.2%). Patients with disease of any of plantar, dorsalis pedis arteries and SAD faced higher risk of CLI (OR=13.25, 95% CI: 1.69-104.16). SAD was associated with diabetes and dialysis (both: OR=4.85; dialysis only: OR=3.60; diabetes only: OR=1.70; none: reference OR; P<0.01), weight (underweight: OR=1.10; normal: reference OR; overweight: OR=0.81; obese: OR=0.60; P=0.03), while women and tobacco smokers were less likely to have SAD (women: OR=0.68; P<0.01; tobacco use: OR=0.54; P<0.01). CONCLUSIONS: SAD was strongly and independently associated with CLI, diabetes and dialysis. Thus, SAD should be regarded as a leading actor in CLI. PMID- 29786412 TI - The use of scoring balloons in the superficial femoral artery. AB - Percutaneous transluminal angioplasty and stenting is becoming increasingly the first-line treatment for patients with both claudication and critical limb ischemia instead of surgery, with the aim of returning the patient's quality of life in the former and preventing amputation. Drug-eluting technologies have seen a large surge in popularity in recent years, and significant patient benefits have been seen with the use of drug-eluting stents and balloons over the use of plain balloon angioplasty. Unfortunately, in many patients with arterial disease there is significant vessel wall calcification - this can theoretically be a barrier to drug delivery and can also be a contributing factor to flow limiting dissection and the subsequent need for bail out stenting. Several studies have looked at the efficacy of scoring balloons to minimize these problems in patients with severe calcification. With increasing use of vascular stents over the last 5 10 years, more cases of in stent stenosis are being seen, and scoring balloons have been postulated to improve outcomes here also. Scoring balloons have been available for many years, having seen first use in the coronary system, but are now being studied in the peripheral arterial landscape, both above and below the popliteal segment. This article will review their use in the superficial femoral artery. PMID- 29786410 TI - Percutaneous deep venous arterialization in patients with critical limb ischemia. AB - BACKGROUND: Critical limb ischemia (CLI) is the presentation of end stage peripheral arterial disease and typically presents with rest pain, ulceration and gangrene. The outcome of conservative treatment is poor and often leads to amputations. Arterial revascularization plays an important role in amputation prevention. Unfortunately, a significant percentage of CLI patients cannot be revascularized and subsequently end up with a palliative amputation. This has led to the need and exploration of new treatment options in this no option subgroup of CLI. Deep venous arterialization (DVA) is one of them and has been reported as a save and feasible novel and promising alternative to amputation. The goal of DVA is to provide arterialized blood in significant volumes and pressure to the plantar venous arch and ischemic tissue to enable wound healing. Selecting the right patients is critical for successful DVA and requires that extra attention is paid to the wounds as well as arterial and venous vascular status. METHODS: The procedure was previously described in our initial experience in the first-in man study performed on 7 patients with NOP-CLI. The angiographic goal of the procedure is to deliver arterialized blood to the plantar venous arch in significant volumes and pressure, circumventing the numerous valves in the process. The clinical goal is to achieve wound healing. RESULTS: Technical success was achieved in all patients. Flow in the plantar arch was achieved in 5 of the 7 patients. One patient with chronic rest pain became pain free within 48 hours after the procedure. Complete wound healing was achieved at 12 months in 5 of the 7 patients. Reinterventions were performed in 5 of 7 patients to maintain patency. Of the 7 study patients, five underwent minor amputation of one or more toes, and two underwent major amputations within 12 months (limb salvage, 71%). CONCLUSIONS: The LimFlow system is currently the only registered device a total percutaneous DVA can be performed with. In addition to the percutaneous creation of an arteriovenous fistula (AVF), it also allows disruption of the veins with a dedicated valvulotome. PMID- 29786413 TI - Frozen elephant trunk and arch endografts for chronic thoracoabdominal aortic dissections. AB - Chronic aortic dissecting aneurysms (TAAD) presenting after acute Stanford type A or B dissection includes both arch and/or thoracoabdominal aortic aneurysms (TAAA). Approximately 60% of patients who survive surgical treatment of acute type A aortic dissections will require another aortic procedure. Similarly, more than 70% of patients with chronic type B aortic dissections will experience false lumen dilation at 5-year follow-up, often requiring intervention. Open or hybrid aortic repairs of complex TAAD involving the arch and the TAAA are very demanding procedures for both patients and clinicians. Open surgery remains the first line therapy in fit patients. Recent development of branched arch devices has offered an alternative option for high-risk patients. Technical challenges associated with the endovascular management of these complex aneurysms include proximal sealing zone often located in the aortic arch or the ascending aorta, narrow true lumen working space, and aortic branch perfusion by either the true or false lumen, or both. Recent studies have reported encouraging results with endovascular treatment of these complex dissecting aneurysms, especially following open ascending aortic repair. The aim of this review was to describe the available strategies for arch repair in the setting of a chronic TAAD and to determine the subset of patients that can benefit from of a totally endovascular approach. PMID- 29786414 TI - Uncovering the Design Principle of Amino Acid-Derived Photoluminescent Biodots with Tailor-Made Structure-Properties and Applications for Cellular Bioimaging. AB - Natural amino acids possess side chains with different functional groups (R groups), which make them excellent precursors for programmable synthesis of biomolecule-derived nanodots (biodots) with desired properties. Herein, we report the first systematic study to uncover the material design rules of biodot synthesis from 20 natural alpha-amino acids via a green hydrothermal approach. The as-synthesized amino acid biodots (AA dots) are comprehensively characterized to establish a structure-property relationship between the amino acid precursors and the corresponding photoluminescent properties of AA dots. It was found that the amino acids with reactive R groups, including amine, hydroxyl, and carboxyl functional groups form unique C-O-C/C-OH and N-H bonds in the AA dots which stabilize the surface defects, giving rise to brightly luminescent AA dots. Furthermore, the AA dots were found to be amorphous and the length of the R group was observed to affect the final morphology (e.g., disclike nanostructure, nanowire, or nanomesh) of the AA dots, which in turn influence their photoluminescent properties. It is noteworthy to highlight that the hydroxyl containing amino acids, that is, Ser and Thr, form the brightest AA dots with a quantum yield of 30.44% and 23.07%, respectively, and possess high photostability with negligible photobleaching upon continuous UV exposure for 3 h. Intriguingly, by selective mixing of Ser or Thr with another amino acid precursor, the resulting mixed AA dots could inherit unique properties such as improved photostability and significant red shift in their emission wavelength, producing enhanced green and red fluorescent intensity. Moreover, our cellular studies demonstrate that the as-synthesized AA dots display outstanding biocompatibility and excellent intracellular uptake, which are highly desirable for imaging applications. We envision that the material design rules discovered in this study will be broadly applicable for the rational selection of amino acid precursors in the tailored synthesis of biodots. PMID- 29786415 TI - Tailoring Crystalline Morphology by High-Efficiency Nucleating Fiber: Toward High Performance Poly(l-lactide) Biocomposites. AB - In this work, a high-melting-point poly(l-lactide) fiber (hPLLA fiber) with high efficiency nucleation activity was prepared and introduced into PLLA matrix to prepare fully biodegradable PLLA biocomposites. The highly active nucleating surfaces of the hPLLA fiber induced chain ordering and lamellar organization, leading to a preferable formation of well-organized PLLA transcrystallinity at the surface of the hPLLA fiber under quiescent conditions. The construction of such compact transcrystallinity increased the crystallinity and enhanced the interfacial adhesion, which largely promoted heat resistance, tensile strength, and barrier property of PLLA biocomposites at a low content of hPLLA fiber. With the addition of 1 wt % hPLLA fiber, the storage modulus of the PLLA biocomposite was enhanced by 82 times from 4 to 330 MPa at 80 degrees C and the oxygen permeability coefficient and water permeability coefficient were decreased by 52 and 51% to be 5.9 * 10-15 cm3.cm/cm2.s.Pa and 4.5 * 10-14 g.cm/cm2.s.Pa, respectively, compared with those of pure PLLA. Moreover, the transparency of PLLA was maintained with the incorporation of hPLLA fiber. Thus, this strategy paved a new way to prepare high-performance and fully biodegradable biocomposites. PMID- 29786416 TI - Zinc Oxide-Enhanced Piezoelectret Polypropylene Microfiber for Mechanical Energy Harvesting. AB - This paper reports zinc oxide (ZnO)-coated piezoelectret polypropylene (PP) microfibers with a structure of two opposite arc-shaped braces for enhanced mechanical energy harvesting. The ZnO film was coated onto PP microfibers via magnetron sputtering to form a ZnO/PP compound structure. Triboelectric Nanogenerator (TENG) based on ZnO/PP microfiber compound film was carefully designed with two opposite arc-shaped braces. The results of this study demonstrated that the mechanical energy collection efficiency of TENG based on piezoelectret PP microfiber was greatly enhanced by the coated ZnO and high voltage corona charging method. We found that, with the step-increased distance of traveling for the movable carbon black electrode, an electrical power with an approximately quadratic function of distance was generated by this mechanical electrical energy conversion, because more PP microfibers were connected to the electrode. Further, with a full contact condition, the peak of the generated voltage, current, and charges based on the ZnO/PP microfibers by this mechanical electrical energy conversion with 1 m/s2 reached 120 V, 3 MUA, and 49 nC, respectively. Moreover, a finger-tapping test was used to demonstrate that the ZnO/PP microfiber TENG is capable of lighting eight light-emitting diodes. PMID- 29786418 TI - Synthesis, Spray Deposition, and Hot-Press Transfer of Copper Nanowires for Flexible Transparent Electrodes. AB - We report a solution-phase approach to the synthesis of crystalline copper nanowires (Cu NWs) with an aspect ratio >1000 via a new catalytic mechanism comprising copper ions. The synthesis involves the reaction between copper(II) chloride and copper(II) acetylacetonate in a mixture of oleylamine and octadecene. Reaction parameters such as the molar ratio of precursors as well as the volume ratio of solvents offer the possibility to tune the morphology of the final product. A simple low-cost spray deposition method was used to fabricate Cu NW films on a glass substrate. Post-treatment under reducing gas (5% H2 + 95% N2) atmosphere resulted in Cu NW films with a low sheet resistance of 24.5 Omega/sq, a transmittance of T = 71% at 550 nm (including the glass substrate), and a high oxidation resistance. Moreover, the conducting Cu NW networks on a glass substrate can easily be transferred onto a polycarbonate substrate using a simple hot-press transfer method without compromising on the electrical performance. The resulting flexible transparent electrodes show excellent flexibility ( R/ Ro < 1.28) upon bending to curvatures of 1 mm radius. PMID- 29786417 TI - Ultraselective Pebax Membranes Enabled by Templated Microphase Separation. AB - Block copolymer materials have been considered as promising candidates to fabricate gas separation membranes. This microphase separation affects the polymer chain packing density and molecular separation efficiency. Here, we demonstrate a method to template microphase separation within a thin composite Pebax membrane, through the controllable self-assembly of one-dimensional halloysite nanotubes (HNTs) within the thin film via the solution-casting technique. Crystallization of the polyamide component is induced at the HNT surface, guiding subsequent crystal growth around the tubular structure. The resultant composite membrane possesses an ultrahigh selectivity (up to 290) for the CO2/N2 gas pair, together with a moderate CO2 permeability (80.4 barrer), being the highest selectivity recorded for Pebax-based membranes, and it easily surpasses the Robeson upper bound. The templated microphase separation concept is further demonstrated with the nanocomposite hollow fiber gas separation membranes, showing its effectiveness of promoting gas selectivity. PMID- 29786419 TI - Multifunctional, High Molecular Weight, Post-Translationally Modified Proteins through Oxidative Cysteine Coupling and Tyrosine Modification. AB - Glycoproteins and their mimics are challenging to produce via chemical or biological methods because of their long protein backbones and large number of polysaccharide side chains that form a densely grafted protein-polysaccharide brush architecture. Herein, we demonstrate a new approach to protein bioconjugate synthesis that can approach the molar mass and functionalization densities of natural glycoproteins such as mucins and aggrecans. In this method, a tyrosine enriched protein sequence is engineered and synthesized in E. coli, and sugars or other functional moieties can be efficiently and polyvalently grafted to the backbone through tyrosine modification chemistry. Cysteine residues on the chain ends are used for oxidative chain polymerization into high molar mass chains larger than can be easily expressed in the host. The effects of tyrosine enrichment and cysteine-incorporation on the physical and expression properties on a model protein are explored. Elastin-like peptides (ELPs) are chosen because of their high expression yields, repetitive sequence, substitutable amino acids, and well-studied physical properties. The sequence modifications to mimic glycoproteins are shown to affect the maximum length of expressible sequence but not yield. The tyrosine modification chemistry is shown to functionalize up to 73% of all tyrosines on the peptide, and the scope of functional groups that can be mass conjugated to proteins is expanded through multistep conjugation strategies involving copper(I)-catalyzed alkyne-azide cycloaddition showing up to 97% alkyne functionalization. All of the functionalization chemistries preserve the ability to polymerize the backbone. PMID- 29786420 TI - Bacteria-Driven Hypoxia Targeting for Combined Biotherapy and Photothermal Therapy. AB - The facultative anaerobe Salmonella strain VNP20009 selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. However, the phase 1 clinical trial of VNP20009 has been terminated mainly due to its weak antitumor effects and exhibition of dose-dependent toxicity. Here, we leveraged the advantages of VNP20009 biotherapy together with polydopamine-mediated photothermal therapy in order to enhance the antitumor efficacy toward malignant melanoma. VNP20009 was coated with polydopamine via oxidation and self-polymerization, which was then injected into tumor-bearing mice via the tail vein. Polydopamine-coated VNP20009 targeted hypoxic areas of the solid tumors, and near-infrared laser irradiation of the tumors induced heating due to polydopamine. This combined approach eliminated the tumors without relapse or metastasis with only one injection and laser irradiation. More importantly, we found both VNP and pDA potentiate the therapeutic ability of each other, resulting in a superior anticancer effect. PMID- 29786421 TI - Enhanced Hydrogen Storage Properties and Reversibility of LiBH4 Confined in Two Dimensional Ti3C2. AB - LiBH4 is of particular interest as one of the most promising materials for solid state hydrogen storage. Herein, LiBH4 is confined into a novel two-dimensional layered Ti3C2 MXene through a facile impregnation method for the first time to improve its hydrogen storage performance. The initial desorption temperature of LiBH4 is significantly reduced, and the de-/rehydrogenation kinetics are remarkably enhanced. It is found that the initial desorption temperature of LiBH4@2Ti3C2 hybrid decreases to 172.6 degrees C and releases 9.6 wt % hydrogen at 380 degrees C within 1 h, whereas pristine LiBH4 only releases 3.2 wt % hydrogen under identical conditions. More importantly, the dehydrogenated products can partially rehydrogenate at 300 degrees C and under 95 bar H2. The nanoconfined effect caused by unique layered structure of Ti3C2 can hinder the particles growth and agglomeration of LiBH4. Meanwhile, Ti3C2 could possess superior effect to destabilize LiBH4. The synergetic effect of destabilization and nanoconfinement contributes to the remarkably lowered desorption temperature and improved de-/rehydrogenation kinetics. PMID- 29786422 TI - Mechanisms Regulating the Association of Protein Phosphatase 1 with Spinophilin and Neurabin. AB - Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homologue neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins. The association between spinophilin and PP1 is increased in the striatum of animal models of Parkinson's disease (PD). However, mechanisms that regulate the association of spinophilin and neurabin with PP1 are unclear. Here, we report that the association between spinophilin and PP1alpha or PP1gamma1 was increased by CDK5 expression and activation in a heterologous cell system. This increased association is at least partially due to phosphorylation of PP1. Conversely, CDK5 expression and activation decreased the association of PP1 with neurabin. As with dopamine depletion, methamphetamine (METH) abuse causes persistent alterations in dopamine signaling which influence striatal medium spiny neuron function and biochemistry. Moreover, both METH toxicity and dopamine depletion are associated with deficits in motor control and motor learning. Pathologically, we observed a decreased association of spinophilin with PP1 in rat striatum evaluated one month following a binge METH paradigm. Behaviorally, we found that loss of spinophilin recapitulates rotarod pathology previously observed in dopamine-depleted and METH-treated animals. Together, these data have implications in multiple disease states associated with altered dopamine signaling such as PD and psychostimulant drug abuse and delineate a novel mechanism by which PP1 interactions with spinophilin and neurabin may be differentially regulated. PMID- 29786423 TI - Electrochemical Determination of TNT, DNT, RDX, and HMX with Gold Nanoparticles/Poly(Carbazole-Aniline) Film-Modified Glassy Carbon Sensor Electrodes Imprinted for Molecular Recognition of Nitroaromatics and Nitramines. AB - Since nitroaromatic- and nitramine-type energetic materials, mostly arising from military activities, are persistent pollutants in soil and groundwater, on-site sensing of these hazardous chemicals has gained importance. A novel electrochemical sensor was designed for detecting nitroaromatic- and nitramine type energetic materials, relying on gold nanoparticles (Aunano), modified glassy carbon (GC) electrode coated with nitro-energetic memory-poly(carbazole-aniline) copolymer (Cz- co-ANI) film (e.g., TNT memory-GC/P(Cz- co-ANI)-Aunano modified electrode). Current was recorded against concentration to build the calibration curves that were found to be linear within the range of 100-1000 MUg L-1 for 2,4,6-trinitrotoluene (TNT) and 2,4-dinitrotoluene (DNT): 50-1000 MUg L-1 for 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro 1,3,5,7-tetrazocine (HMX). The corresponding limits of detection were 25 MUg L-1 for TNT, 30 MUg L-1 for DNT, and 10 MUg L-1 for both RDX and HMX, using nitro energetic memory-GC/P(Cz- co-ANI)-Aunano electrodes. These electrodes were used separately, and specific determinations were made in various mixtures of nitro energetic materials. The developed method could be efficiently used in electroanalyzing nitroaromatics and nitramines in military explosives (i.e., comp B, octol, and comp A5). The sensor electrodes were specific for the tested nitro energetic compounds and did not respond to paracetamol-caffeine-based analgesic drug, acetylsalicylic acid (aspirin), sweetener, and sugar that can be used as camouflage materials in passenger belongings. The developed method was statistically validated against the standard LC-MS reference method in contaminated clay soil samples containing TNT and RDX explosives. PMID- 29786424 TI - Tuning Gene Activity by Inducible and Targeted Regulation of Gene Expression in Minimal Bacterial Cells. AB - Functional genomics studies in minimal mycoplasma cells enable unobstructed access to some of the most fundamental processes in biology. Conventional transposon bombardment and gene knockout approaches often fail to reveal functions of genes that are essential for viability, where lethality precludes phenotypic characterization. Conditional inactivation of genes is effective for characterizing functions central to cell growth and division, but tools are limited for this purpose in mycoplasmas. Here we demonstrate systems for inducible repression of gene expression based on clustered regularly interspaced short palindromic repeats-mediated interference (CRISPRi) in Mycoplasma pneumoniae and synthetic Mycoplasma mycoides, two organisms with reduced genomes actively used in systems biology studies. In the synthetic cell, we also demonstrate inducible gene expression for the first time. Time-course data suggest rapid kinetics and reversible engagement of CRISPRi. Targeting of six selected endogenous genes with this system results in lowered transcript levels or reduced growth rates that agree with lack or shortage of data in previous transposon bombardment studies, and now produces actual cells to analyze. The ksgA gene encodes a methylase that modifies 16S rRNA, rendering it vulnerable to inhibition by the antibiotic kasugamycin. Targeting the ksgA gene with CRISPRi removes the lethal effect of kasugamycin and enables cell growth, thereby establishing specific and effective gene modulation with our system. The facile methods for conditional gene activation and inactivation in mycoplasmas open the door to systematic dissection of genetic programs at the core of cellular life. PMID- 29786425 TI - Comprehensive Study of the Evolution of the Gas-Liquid Partitioning of Acetaldehyde during Wine Alcoholic Fermentation. AB - Determining the gas-liquid partitioning ( Ki) of acetaldehyde during alcoholic fermentation is an important step in the optimization of fermentation control with the aim of minimizing the accumulation of this compound, which is responsible for the undesired attributes of green apples and fresh-cut grass in wines. In this work, the effects of the main fermentation parameters on the Ki of acetaldehyde were assessed. Ki values were found to be dependent on the temperature and composition of the medium. A nonlinear correlation between the evolution of the Ki and fermentation progress was observed, attributable to the strong retention effect of ethanol at low concentrations, and it was demonstrated that the partitioning of this specific molecule was not influenced by the CO2 production rate. A model was developed that quantifies the Ki of acetaldehyde with a very accurate prediction, as the difference between the observed and predicted values did not exceed 9%. PMID- 29786426 TI - Influence of Enzyme Quantity and Distribution on the Self-Propulsion of Non-Janus Urease-Powered Micromotors. AB - The use of enzyme catalysis to power micro- and nanomachines offers unique features such as biocompatibility, versatility, and fuel bioavailability. Yet, the key parameters underlying the motion behavior of enzyme-powered motors are not completely understood. Here, we investigate the role of enzyme distribution and quantity on the generation of active motion. Two different micromotor architectures based on either polystyrene (PS) or polystyrene coated with a rough silicon dioxide shell (PS@SiO2) were explored. A directional propulsion with higher speed was observed for PS@SiO2 motors when compared to their PS counterparts. We made use of stochastically optical reconstruction microscopy (STORM) to precisely detect single urease molecules conjugated to the micromotors surface with a high spatial resolution. An asymmetric distribution of enzymes around the micromotor surface was observed for both PS and PS@SiO2 architectures, indicating that the enzyme distribution was not the only parameter affecting the motion behavior. We quantified the number of enzymes present on the micromotor surface and observed a 10-fold increase in the number of urease molecules for PS@SiO2 motors compared to PS-based micromotors. To further investigate the number of enzymes required to generate a self-propulsion, PS@SiO2 particles were functionalized with varying amounts of urease molecules and the resulting speed and propulsive force were measured by optical tracking and optical tweezers, respectively. Surprisingly, both speed and force depended in a nonlinear fashion on the enzyme coverage. To break symmetry for active propulsion, we found that a certain threshold number of enzymes molecules per micromotor was necessary, indicating that activity may be due to a critical phenomenon. Taken together, these results provide new insights into the design features of micro/nanomotors to ensure an efficient development. PMID- 29786427 TI - Induction of Apoptosis in Human Papillary-Thyroid-Carcinoma BCPAP Cells by Diallyl Trisulfide through Activation of the MAPK Signaling Pathway. AB - This study aimed to elucidate the potential effects of diallyl trisulfide (DATS) on human papillary-thyroid-carcinoma BCPAP cells and its underlying mechanisms. DATS is an organosulfur compound derived from garlic. In this study, we demonstrated that compared with the solvent control, DATS treatment at concentrations of 5, 10, and 20 MUMU decreased cell survival rates of BCPAP cells to 84.51 +/- 2.67, 57.16 +/- 1.18, and 41.22 +/- 1.19% respectively. DATS also caused cell-cycle arrest at G0/G1 phase, and the proportion of cells arrested in G0/G1 phase rose from 68.8 +/- 8.38 to 80.4 +/- 8.38%, which eventually resulted in cell apoptosis through a mitochondrial apoptotic pathway in BCPAP cells. Further evidence showed that DATS activated ERK, JNK, and p38, members of the MAPK family. Moreover, ERK and JNK inhibitors partially reversed apoptosis in BCPAP cells induced by DATS treatment. Taken together, our results demonstrated that DATS exerted an apoptosis-inducing effect on papillary-thyroid-cancer cells via activation of the MAPK signaling pathway, which shed light on a prospective therapeutic target for thyroid-cancer treatment. PMID- 29786428 TI - Electrochemical Impedance Spectroscopy for Real-Time Detection of Lipid Membrane Damage Based on a Porous Self-Assembly Monolayer Support. AB - Layer-by-layer dissolution and permeable pore formation are two typical membrane damage pathways, which induce membrane function disorder and result in serious disease, such as Alzheimer's disease, Keshan disease, Sickle-cell disease, and so on. To effectively distinguish and sensitively monitor these two typical membrane damage pathways, a facile electrochemical impedance strategy was developed on a porous self-assembly monolayer (pSAM) supported bilayer lipid membrane (BLM). The pSAM was prepared by selectively electrochemical reductive desorption of the mercaptopropionic acid in a mixed mercaptopropionic acid/11-mercaptoundecanoic acid self-assembled monolayer, which created plenty of nanopores with tens of nanometers in diameter and several nanometers in height (defined as inner-pores). The ultralow aspect ratio of the inner-pores was advantageous to the mass transfer of electrochemical probe [Fe(CN)6]3-/4-, simplifying the equivalent electric circuit for electrochemical impedance spectroscopy analysis at the electrode/membrane interface. [Fe(CN)6]3-/4- transferring from the bulk solution into the inner-pore induce significant changes of the interfacial impedance properties, improving the detection sensitivity. Based on these, the different membrane damage pathways were effectively distinguished and sensitively monitored with the normalized resistance-capacitance changes of inner-pore-related parameters including the electrolyte resistance within the pore length ( Rpore) and the metal/inner-pore interfacial capacitance ( Cpore) and the charge-transfer resistance ( Rct-in) at the metal/inner-pore interface. PMID- 29786429 TI - Development of a Nanostructured alpha-MnO2/Carbon Paper Composite for Removal of Ni2+/Mn2+ Ions by Electrosorption. AB - Toxic metal ions, such as Ni2+ and Mn2+, in industrial waste streams are nonbiodegradable and can cause damage to the human body. Electrochemical cleaning techniques are attractive as they offer more control and produce less sludge than do chemical/biological approaches without the high pressures needed for membranes. Here, nanoneedle-structured alpha-MnO2/carbon fiber paper (CFP) composites were synthesized by a hydrothermal approach and used as electrodes for combined electroadsorption and capacitive deionization removal of nickel and manganese ions from pseudoindustrial waste streams. The specific performance of alpha-MnO2/CFP (16.4 mg Ni2+ per g of active material) not only shows a great improvement in comparison with its original CFP substrate (0.034 Ni2+ mg per g), but also is over 6 times that of activated carbon (2.5 mg Ni2+ per g). The high performance of alpha-MnO2/CFP composites is attributed to their high surface area, desirable mesoporosity, pore-size distribution that permits the further access of ions, and their property as a pseudocapacitor, which contributes to a more efficient electron/charge transfer in the faradic process. Unfortunately, it was also found that some Mn2+ ions are released due to the partial reduction of MnO2 when operated as a negative electrode. For the removal of Mn2+ ions, an asymmetric arrangement, consisting of a MnO2/CFP positive electrode and an activated carbon negative electrode, was employed. This arrangement reduced the Mn2+ concentration from 100 ppm to less than 2 ppm, a vast improvement over the systematical two-activated carbon electrode system that could only reach 42 ppm under the same conditions. It was also observed that as long as the MnO2/CFP composite was maintained as a positive electrode, it was completely stable. The technique was able to reduce both Ni2+ and Mn2+ ions to well below the 10 ppm requirement for discharge into public sewers in Singapore. PMID- 29786430 TI - GalaxyGPCRloop: Template-Based and Ab Initio Structure Sampling of the Extracellular Loops of G-Protein-Coupled Receptors. AB - The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In this study, a new ECL2 conformational sampling method involving both template-based and ab initio sampling was developed. Inspired by the observation of similar ECL2 structures of closely related GPCRs, a template-based sampling method employing loop structure templates selected from the structure database was developed. A new metric for evaluating similarity of the target loop to templates was introduced for template selection. An ab initio loop sampling method was also developed to treat cases without highly similar templates. The ab initio method is based on the previously developed fragment assembly and loop closure method. A new sampling component that takes advantage of secondary structure prediction was added. In addition, a conserved disulfide bridge restraining ECL2 conformation was predicted and analytically incorporated into sampling, reducing the effective dimension of the conformational search space. The sampling method was combined with an existing energy function for comparison with previously reported loop structure prediction methods, and the benchmark test demonstrated outstanding performance. PMID- 29786431 TI - Ultrasonic-Assisted Spin-Coating: Improved Junction by Enhanced Permeation of a Coating Material within Nanostructures. AB - Over the last decades, the spin-coating (SC) technique has been widely used to prepare thin films of various materials in the liquid phase on arbitrary substrates. The technique simply relies on the centrifugal force to spread a coating solution radially outward over the substrate. This mechanism works fairly well for solutions with low surface tension to form thin films of reasonable junctions on smooth substrates. Here, we present a modified SC technique, namely, ultrasonic-assisted spin-coating (UASC), to form thin films of coating solution having high surface tension on rough substrates with excellent junctions. The UASC technique couples SC with an external ultrasonic wave generator to provide external perturbation to locally break down big drops of the coating material into smaller droplets via Rayleigh instability. Because of their lower mass, these tiny droplets gain low momenta and move slowly both in radial and azimuthal directions, giving them an enough time to effectively permeate within pores, thereby yielding excellent junctions. Furthermore, we also investigated the effect of junction improvement on conventional and inverted bulk heterojunction organic solar cells. Intriguingly, the organic solar cells fabricated by the UASC method showed an improved efficiency compared to typical SC owing to efficient charge transfer across the junction. These results clearly imply that UASC is a simple and powerful technique which can significantly enhance the device performance by improving the junction. Moreover, we believe that UASC can be more effective for the preparation of devices composed of multilayers of different materials having complicated nanostructures. PMID- 29786432 TI - Modular Design of Fluorescent Dibenzo- and Naphtho-Fluoranthenes: Structural Rearrangements and Electronic Properties. AB - A library of 12 dibenzo- and naphtho-fluoranthene polycyclic aromatic hydrocarbons (PAHs) with MW = 302 (C24H14) was synthesized via a Pd-catalyzed fluoranthene ring-closing reaction. By understanding the various modes by which the palladium migrates during the transformation, structural rearrangements were bypassed, obtaining pure PAHs in high yields. Spectroscopic and electrochemical characterization demonstrated the profound diversity in the electronic structures between isomers. Highlighting the significant differences in emission of visible light, this library of PAHs will enable their standardization for toxicological assessment and potential use as optoelectronic materials. PMID- 29786433 TI - Polymer Diffusion in the Interphase Between Surface and Solution. AB - Total internal reflection fluorescence correlation spectroscopy (TIR-FCS) is applied to study the self-diffusion of poly(ethylene glycol) solutions in the presence of weakly attractive interfaces. Glass coverslips modified with aminopropyl- and propyl-terminated silanes are used to study the influence of solid surfaces on polymer diffusion. A model of three phases of polymer diffusion allows to describe the experimental fluorescence autocorrelation functions. Besides the two-dimensional diffusion of adsorbed polymer on the substrate and three-dimensional free diffusion in bulk solution, a third diffusion time scale is observed with intermediate diffusion times. This retarded three-dimensional diffusion in the solution is assigned to the long-range effects of solid surfaces on diffusional dynamics of polymers. The respective diffusion constants show Rouse scaling ( D ~ N-1), indicating a screening of hydrodynamic interactions by the presence of the surface. Hence, the presented TIR-FCS method proves to be a valuable tool to investigate the effect of surfaces on polymer diffusion beyond the first adsorbed polymer layer on the 100 nm length scale. PMID- 29786434 TI - Ion Imaging of MgI+ Photofragment in Ultraviolet Photodissociation of Mass Selected Mg+ICH3 Complex. AB - We have observed images of MgI+ fragment ions produced in ultraviolet laser photodissociation of mass-selected Mg+ICH3 ions at 266 nm. Split distribution almost perpendicular to the polarization direction of the photolysis laser was observed in the photofragment image. Potential energy curves of Mg+ICH3 were obtained by theoretical calculations. Among these curves, the excited complex ion dissociated along almost repulsive potentials with several avoided crossings, which was connected to MgI+ + CH3. In the ground state of Mg+ICH3, the CH3I was bonded with Mg from the iodine side, and the Mg-I-C bond angle was calculated to be 101.1 degrees . The theoretical results also indicated that the dissociation occurred after the 52A' <- 12A' photoexcitation, where the transition dipole moment was almost parallel to the Mg-I bond axis. The MgI+ and CH3 fragments dissociated each other parallel to the direction connecting those center-of masses, which was 67 degrees with respect to the transition dipole moment of 52A' <- 12A' photoexcitation. Therefore, the fragment recoil direction was assumed to approach perpendicular tendency against the polarization direction under the fast dissociation process. However, calculated potential energy curves showed a complicated reaction pathway for MgI+ production, including nonadiabatic processes, although the experimental results indicated the fast dissociation reaction. PMID- 29786435 TI - Asymmetric Construction of a Multi-Pharmacophore-Containing Dispirotriheterocyclic Scaffold and Identification of a Human Carboxylesterase 1 Inhibitor. AB - A catalytic asymmetric [3 + 2] cyclization of novel 4-isothiocyanato pyrazolones and isatin-derived ketimines was developed, delivering a wide range of intriguing dispirotriheterocyclic products in high yield with excellent diastereoselectivity and enantioselectivity. A chiral sulfoxide derivative of this dispirocyclic product was identified to be a promising hit of the human carboxylesterase 1 inhibitor, and the significant difference of the activity between two enantiomers emphasized the importance of this asymmetric process. PMID- 29786437 TI - Cobalt-Catalyzed Oxidative C(sp3)-H Phosphonylation for alpha-Aminophosphonates via C(sp3)-H/P(O)-H Coupling. AB - The first oxidative C(sp3)-H phosphonylation of tertiary aliphatic amines has been developed. The use of cobalt acetate as a catalyst, N-hydroxyphthalimide as a cocatalyst, and air as an oxidant enabled the conversion of tertiary aromatic and aliphatic amines into alpha-aminophosphonates in moderate to excellent yields under mild conditions via a cross dehydrogenative coupling reaction. PMID- 29786436 TI - Cytotoxic and Antibacterial Eremophilane Sesquiterpenes from the Marine-Derived Fungus Cochliobolus lunatus SCSIO41401. AB - Three new eremophilane sesquiterpenes, dendryphiellins H-J (1-3), and three new phthalide natural products (4-6) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Dendryphiellin I (2) showed cytotoxic and antibacterial activities against five cancer cell lines (IC50 1.4 to 4.3 MUM) and three bacterial species (MIC 1.5 to 13 MUg/mL), respectively. Dendryphiellin J (3), a rare naturally occurring aldoxime analogue, displayed cytotoxicities against ACHN and HepG-2 cells with IC50 values of 3.1 and 5.9 MUM, respectively. Further studies indicated that 3 induced apoptosis in ACHN cells in a dose- and time-dependent manner. PMID- 29786439 TI - A Class of Amide Ligands Enable Cu-Catalyzed Coupling of (Hetero)aryl Halides with Sulfinic Acid Salts under Mild Conditions. AB - The amide derived from 4-hydroxy-l-proline and 2,6-dimethylaniline is a powerful ligand for Cu-catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing the formation of a wide range of (hetero)aryl sulfones from the corresponding (hetero)aryl halides at considerably low catalytic loadings. The coupling of (hetero)aryl iodides and sodium methanesulfinate proceeds at room temperature with only 0.5 mol % CuI and ligand, representing the first example for Cu-catalyzed arylation at both low catalytic loading and room temperature. PMID- 29786438 TI - An Accessible Method for DFT Calculation of 11B NMR Shifts of Organoboron Compounds. AB - The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of 11B NMR. However, the identification and characterization of reaction intermediates in often complex systems is far from trivial, as 11B NMR does not provide any detailed structural information. Greater insight into the structures present in such systems can be obtained by using DFT chemical shift calculations to support or exclude proposed reaction intermediates. In this article, we report a rapid and accessible approach to the calculation of 11B NMR shifts that is applicable to a wide range of organoboron compounds. PMID- 29786440 TI - Surface Ligand Promotion of Carbon Dioxide Reduction through Stabilizing Chemisorbed Reactive Intermediates. AB - We have explored functionalizing metal catalysts with surface ligands as an approach to facilitate electrochemical carbon dioxide reduction reaction (CO2RR). To provide a molecular level understanding of the mechanism by which this enhancement occurs, we combine in situ spectroscopy analysis with an interpretation based on quantum mechanics (QM) calculations. We find that a surface ligand can play a critical role in stabilizing the chemisorbed CO2, which facilitates CO2 activation and leads to a 0.3 V decrease in the overpotential for carbon monoxide (CO) formation. Moreover, the presence of the surface ligand leads to nearly exclusive CO production. At -0.6 V (versus reversible hydrogen electrode, RHE), CO is the only significant product with a faradic efficiency of 93% and a current density of 1.9 mA cm-2. This improvement corresponds to 53-fold enhancement in turnover frequency compared with the Ag nanoparticles (NPs) without surface ligands. PMID- 29786441 TI - X-ray Photoelectron Spectroscopy Studies of Nanoparticles Dispersed in Static Liquid. AB - For nanoparticles active for chemical and energy transformations in static liquid environment, chemistries of surface or near-surface regions of these catalyst nanoparticles in liquid are crucial for fundamentally understanding their catalytic performances at a molecular level. Compared to catalysis at a solid-gas interface, there is very limited information on the surface of these catalyst nanoparticles under a working condition or during catalysis in liquid. Photoelectron spectroscopy is a surface-sensitive technique; however, it is challenging to study the surfaces of catalyst nanoparticles dispersed in static liquid because of the short inelastic mean free path of photoelectrons traveling in liquid. Here, we report a method for tracking the surface of nanoparticles dispersed in static liquid by employing graphene layers as an electron transparent membrane to separate the static liquid containing a solvent, catalyst nanoparticles, and reactants from the high-vacuum environment of photoelectron spectrometers. The surfaces of Ag nanoparticles dispersed in static liquid sealed in such a graphene membrane liquid cell were successfully characterized using a photoelectron spectrometer equipped with a high vacuum energy analyzer. With this method, the surface of catalyst nanoparticles dispersed in liquid during catalysis at a relatively high temperature up to 150 degrees C can be tracked with photoelectron spectroscopy. PMID- 29786442 TI - Synthesis of C-Glycoinositols from C-Glycosylcrotylstannanes. AB - A strategy for the synthesis of C-pseudodisaccharides that centers on the reaction of a C-linked crotyltin and a substituted pent-4-enal and a ring-closing metathesis-alkene dihydroxylation sequence on the derived crotylation products is illustrated in the preparation of analogues of the insulin modulatory inositol galactosamine-beta-(1 -> 4)-3-O-methyl-d- chiro-inositol (beta-INS-2). The modularity of this approach and versatility of the pivotal crotylation products make this a potentially general methodology for diverse libraries of C glycoinositols. PMID- 29786443 TI - Experimental Study of the Structural Effect on the Nanosecond Nonlinear Optical Response of O-Doped Polycyclic Aromatic Hydrocarbons. AB - The nonlinear optical response of some O-doped polycyclic aromatic hydrocarbons (PAHs) is systematically investigated in the present work aiming to understand the influence of structural effects on their nonlinear optical response. In that view, the third-order nonlinear optical properties of these PAHs were measured under 4 ns visible (532 nm) and infrared (1064 nm) laser excitation. The O-doped PAHs were found to exhibit large saturable absorption and negative sign nonlinear refraction under visible excitation, increasing both with the addition of naphthalene units and with the number of O atoms. Their nonlinear optical response was found to be negligible under infrared excitation. Similar measurements performed on thin films of these PAHs have shown that they maintain their large nonlinear optical response even in the solid state, confirming their high potential for optoelectronic and photonic applications. PMID- 29786444 TI - Exploring the Confinement Effect of Carbon Nanotubes on the Electrochemical Properties of Prussian Blue Nanoparticles. AB - A novel and efficient photochemical method has been proposed for the encapsulation of Prussian blue nanoparticles (PBNPs) inside the channels of carbon nanotubes (PB-in-CNTs) in an acidic ferrocyanide solution under UV/vis illumination, and the confinement effect of CNTs on the electrochemical properties of PBNPs is systematically explored. PB-in-CNTs show a faster electron transfer process, an enhanced electrocatalytic activity toward the reduction of H2O2, and an increased anti-base ability compared to PBNPs loaded outside of CNTs (PB-out-CNTs). In addition, PB-in-CNTs show an increased electrochemical reversibility and an unexpected diameter-independent catalytic activity with the decrease of CNT diameters. The improved electrochemical properties of PB-in-CNTs are attributed to the modified electronic properties and dimensions of PBNPs induced by the confinement effect of CNTs. This work provides further insights into the confinement effect on the properties of nanomaterials and will inspire extensive relevant investigations in the development of novel composites or excellent catalysts. PMID- 29786445 TI - Iron-Catalyzed Dehydrative Alkylation of Propargyl Alcohol with Alkyl Peroxides To Form Substituted 1,3-Enynes. AB - This paper reports a new method for the generation of substituted 1,3-enynes, whose synthesis by other methods could be a challenge. The dehydrative decarboxylative cascade coupling reaction of propargyl alcohol with alkyl peroxides is enabled by an iron catalyst and alkylating reagents. Primary, secondary, and tertiary alkyl groups can be introduced into 1,3-enynes, affording various substituted 1,3-enynes in moderate to good yields. Mechanistic studies suggest the involvement of a radical-polar crossover pathway. PMID- 29786446 TI - Total Synthesis of the Marine Phosphomacrolide, (-)-Enigmazole A, Exploiting Multicomponent Type I Anion Relay Chemistry (ARC) in Conjunction with a Late Stage Petasis-Ferrier Union/Rearrangement. AB - An effective late-stage large-fragment union/rearrangement exploiting the Petasis Ferrier protocol, in conjunction with multicomponent Type I Anion Relay Chemistry (ARC) to access advanced intermediates, permits completion of a convergent, stereocontrolled total synthesis of the architecturally complex phosphomacrolide (-)-enigmazole A (1). PMID- 29786448 TI - Serum RBP4 positively correlates with triglyceride level but not with BMI, fat mass and insulin resistance in healthy obese and non-obese individuals. AB - PURPOSE: Retinol binding protein 4 (RBP4) has recently been identified as an adipokine possibly involved in the development of impaired glucose metabolism. We aimed to test serum RBP4 in healthy non-obese individuals and in patients with well-characterized phenotype: obesity without confounding effects of diabetes, metabolic syndrome or dyslipidaemia. Additionally, we examined whether serum RBP4 is associated with anthropometric parameters, insulin resistance and blood lipid parameters. PATIENTS AND METHODS: Twenty-eight patients with obesity and no co morbidities and twenty-five age-matched lean controls were recruited. Anthropometric parameters, body composition, fasting blood lipid profile, RBP4, glucose and insulin were assessed and HOMA-IR was calculated. RESULTS: Mean concentration of RBP4 did not differ between studied groups (in obese patients was 33.93 +/- 4.46 ug/ml and 32.53 +/- 2.53 ug/ml in non-obese controls). RBP4 positively correlated with serum triglycerides in obese and non-obese individuals (r = 0.74, p = 0.03 and r = 0.62, p = 0.02, respectively) and did not show any significant associations with HOMA-IR, anthropometric and body composition parameters. CONCLUSIONS: Excessive adiposity without co-morbidities is not associated with higher levels of circulating RBP4. Serum RBP4 cannot be considered as a direct predictive marker for impaired glucose metabolism. RBP4 possibly contributes to lipid metabolism. PMID- 29786447 TI - Thickness-Tunable Synthesis of Ultrathin Type-II Dirac Semimetal PtTe2 Single Crystals and Their Thickness-Dependent Electronic Properties. AB - The recent discovery of topological semimetals has stimulated extensive research interest due to their unique electronic properties and novel transport properties related to a chiral anomaly. However, the studies to date are largely limited to bulk crystals and exfoliated flakes. Here, we report the controllable synthesis of ultrathin two-dimensional (2D) platinum telluride (PtTe2) nanosheets with tunable thickness and investigate the thickness-dependent electronic properties. We show that PtTe2 nanosheets can be readily grown, using a chemical vapor deposition approach, with a hexagonal or triangular geometry and a lateral dimension of up to 80 MUm, and the thickness of the nanosheets can be systematically tailored from over 20 to 1.8 nm by reducing the growth temperature or increasing the flow rate of the carrier gas. X-ray-diffraction, transmission electron microscopy, and electron-diffraction studies confirm that the resulting 2D nanosheets are high-quality single crystals. Raman spectroscopic studies show characteristics Eg and A1g vibration modes at ~109 and ~155 cm-1, with a systematic red shift with increasing nanosheet thickness. Electrical transport studies show the 2D PtTe2 nanosheets display an excellent conductivity up to 2.5 * 106 S m-1 and show strong thickness-tunable electrical properties, with both the conductivity and its temperature dependence varying considerably with the thickness. Moreover, 2D PtTe2 nanosheets show an extraordinary breakdown current density up to 5.7 * 107 A/cm2, the highest breakdown current density achieved in 2D metallic transition-metal dichalcogenides to date. PMID- 29786449 TI - Fault Detection Based on Near-Infrared Spectra for the Oil Desalting Process. AB - The fault detection problem of the oil desalting process is investigated in this paper. Different from the traditional fault detection approaches based on measurable process variables, near-infrared (NIR) spectroscopy is applied to acquire the process fault information from the molecular vibrational signal. With the molecular spectra data, principal component analysis was explored to calculate the Hotelling T2 and squared prediction error, which act as fault indicators. Compared with the traditional fault detection approach based on measurable process variables, NIR spectra-based fault detection illustrates more sensitivity to early failure because of the fact that the changes in the molecular level can be identified earlier than the physical appearances on the process. The application results show that the detection time of the proposed method is earlier than the traditional method by about 200 min. PMID- 29786451 TI - Annexin A2 is a Robo4 ligand that modulates ARF6 activation-associated cerebral trans-endothelial permeability. AB - Blood-brain barrier (BBB) disruption in neurological disorders remains an intractable problem with limited therapeutic options. Here, we investigate whether the endothelial cell membrane protein annexin A2 (ANXA2) may play a role in reducing trans-endothelial permeability and maintaining cerebrovascular integrity after injury. Compared with wild-type mice, the expression of cerebral endothelial junctional proteins was reduced in E15.5 and adult ANXA2 knockout mice, along with increased leakage of small molecule tracers. In human brain endothelial cells that were damaged by hypoxia plus IL-1beta, treatment with recombinant ANXA2 (rA2) rescued the expression of junctional proteins and decreased trans-endothelial permeability. These protective effects were mediated in part by interactions with F-actin and VE-cadherin, and the ability of rA2 to modulate signaling via the roundabout guidance receptor 4 (Robo4)-paxillin-ADP ribosylation factor 6 (ARF6) pathway. Taken together, these observations suggest that ANXA2 may be associated with the maintenance of endothelial tightness after cerebrovascular injury. ANXA2-mediated pathways should be further explored as potential therapeutic targets for protecting the BBB in neurological disorders. PMID- 29786452 TI - Identification of a Novel HIV-1 Unique Recombinant Form Comprising CRF01_AE, Subtype B', and CRF65_cpx Among Men Who Have Sex with Men in Jilin, China. AB - The current HIV-1 epidemic in China is featured by diverse subtypes and continual emergence of new recombinant viruses. This study identified a novel unique recombinant form (URF), JL16013, among men who have sex with men (MSM) in Jilin, China. The JL16013 virus was different from all known subtypes and set up a distinct branch on the phylogenetic tree. This virus had a CRF01_AE backbone with two subtype B' fragments and one CRF65_cpx fragment inserted into gag, pol, env, and nef regions, suggesting that this novel URF might have originated from the CRF01_AE, subtype B', and CRF65_cpx viruses that were cocirculating in Jilin province. This was the first report of the CRF01_AE/B'/CRF65_cpx recombinant in China. Identification of this URF indicated the severity and complexity of the HIV-1 epidemic among MSM in Jilin province. Timely surveillance of new HIV-1 infections and new recombinants among the MSM population is urgently required. PMID- 29786453 TI - Cross-cultural adaptation and psychometric evaluation of the Singapore version of the Chedoke Arm and Hand Activity. AB - PURPOSE: To develop a Singapore version of the Chedoke Arm and Hand Activity Inventory (CAHAI) and to estimate the construct validity and inter-rater reliability. MATERIALS AND METHODS: The Translation and Cross-Cultural Adaptation of Objectively Assessed Outcome measure procedure was used to systematically adapt the CAHAI. We recruited 56 adults admitted to an inpatient stroke facility to evaluate the psychometric properties of the Singapore version of the CAHAI. The Singapore version of the CAHAI, Fugl-Meyer Assessment of Upper Extremity (FMA UE), and the Action Research Arm Test (ARAT) were administered to all participants. We used Spearman's rank correlation coefficients to estimate convergent and discriminative validity, and reliability was estimated using the intra-class correlation coefficient and standard error of measurement. RESULTS: Implementation of the Translation and Cross-Cultural Adaptation of Objectively Assessed Outcome measure procedure resulted in the modification to two test items. The Singapore version of the CAHAI demonstrated convergent validity with the FMA-UE (rs = 0.87; 95% CI: 0.76, 0.92) and ARAT (rs = 0.80; 95% CI: 0.63, 0.9). Discriminative validity between the Singapore version of the CAHAI and FMA UE pain subscale was rs= 0.42 (95% CI: 0.22, 0.59). Reliability of the Singapore version of the CAHAI was 0.97 (95% CI: 0.94, 0.99) and standard error of measurement of 4.80 points (95% CI: 4.23, 5.55). CONCLUSION: The Singapore version of the CAHAI demonstrated good validity and reliability, similar to the properties of the original CAHAI. Implications for rehabilitation The Singapore version of the Chedoke Arm and Hand Activity Inventory demonstrates evidence of construct validity and inter-rater reliability. The Singapore version of the Chedoke Arm and Hand Activity Inventory can be used by clinicians and researchers to evaluate function in the affected upper extremity for persons with stroke in Singapore. PMID- 29786450 TI - Atrial fibrillation symptom clusters and associated clinical characteristics and outcomes: A cross-sectional secondary data analysis. AB - BACKGROUND:: Symptom clusters among adults with atrial fibrillation have previously been identified but no study has examined the relationship between symptom clusters and outcomes. AIMS:: The purpose of this study was to identify atrial fibrillation-specific symptom clusters, characterize individuals with each cluster, and determine whether symptom cluster membership is associated with healthcare utilization. METHODS:: This was a cross-sectional secondary data analysis of 1501 adults from the Vanderbilt Atrial Fibrillation Registry with verified atrial fibrillation. Self-reported symptoms were measured with the University of Toronto Atrial Fibrillation Severity Scale. We used hierarchical cluster analysis (Ward's method) to identify clusters and dendrograms, pseudo F, and pseudo T-squared to determine the ideal number of clusters. Next, we used regression analysis to examine the association between cluster membership and healthcare utilization. RESULTS:: Males predominated (67%) and the average age was 58.4 years. Two symptom clusters were identified, a Weary cluster (3.7%, n=56, fatigue at rest, shortness of breath at rest, chest pain, and dizziness) and an Exertional cluster (32.7%, n=491, shortness of breath with activity and exercise intolerance). Several sociodemographic and clinical characteristics varied by symptom cluster group membership, including age, gender, atrial fibrillation type, body mass index, comorbidity status, and treatment strategy. Women were more likely to experience either cluster ( p<0.001). The Weary cluster was associated with nearly triple the rate of emergency department utilization (incident rate ratio [IRR] 2.8, p<0.001) and twice the rate of hospitalizations (IRR 1.9, p<0.001). CONCLUSION:: We identified two symptom clusters. The Weary cluster was associated with a significantly increased rate of healthcare utilization. PMID- 29786454 TI - Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome. AB - Preterm neonates with respiratory distress syndrome (RDS) are at increased risk of acute kidney injury (AKI). Our study aimed at determining whether serum cystatin C (sCysC) on day 3 of life (D3) can early predict AKI in preterm neonates with RDS. This prospective study was conducted on 75 preterm neonates; 50 with RDS and 25 without RDS. On D3, sCysC, serum creatinine (sCr) and blood urea nitrogen (BUN) were measured and estimated glomerular filtration rate (eGFR) was calculated. sCr and BUN levels were measured again on days 5 and 7. Neonates were evaluated for development of AKI during first week of life according to the modified pediatric RIFLE (pRIFLE) criteria. Thirteen neonates with RDS developed AKI (26%).There was no significant difference between RDS and control groups with respect to sCysC. RDS neonates with AKI had significantly higher sCysC than those without AKI (1.62 +/- 0.12 versus 1.16 +/- 0.09 mg/l; p < .001). RDS grade III-IV neonates had significantly higher sCysC than RDS grade I-II. There was a significant positive correlation between D3 sCysC and (D5 and D7 sCr and BUN). Receiver operating characteristic (ROC) curve showed that D3 sCysC can predict AKI in preterm neonates with RDS at a cutoff point of >1.3 mg/l with sensitivity of 92.30% and specificity of 96%. We conclude that neonates with RDS are at increased risk of AKI. sCysC on day 3 of life can predict AKI earlier than Cr and eGFR. PMID- 29786456 TI - What everybody should know about postural changes. AB - Posture changes have been known for a long time to influence the concentration of many analytes in blood especially macromolecules. It is very clear that when someone switches from supine to sitting or standing or from sitting to standing a hemoconcentration is induced. Similarly, when someone switches from standing to sitting or lying a hemodilution occurs. In the context of clinical chemistry, rules have been issued to buffer the impact of postural changes close to the blood specimen collection (e.g. 15 min of seated rest before the blood puncture). A big work has then been performed to educate the personnel concerned by blood specimen collection (medical doctors, nurses, phlebotomists, pharmacists, clinical researchers, scientists, etc.) through professional training to standardize the puncture and the collection procedures. Official procedures and guidelines have been published. Nevertheless, there is still a long way to go and too often standardization of posture before the blood collection is not properly performed. Maybe, this relative failure could be overcome by using new strategies in forwarding the message on the impact of posture changes in the outcome of blood tests and the importance of controlling this factor when blood specimens are taken. Some possible actions are presented concerning the improvement of the education of medical and paramedical personnel especially during their primary training, and also to educate the patients and the whole population in general. PMID- 29786455 TI - Estimation of bone mineral density and breaking strength of laying hens based on scans of computed tomography for body composition analysis. AB - 1. The objective of this study was to evaluate the prediction potential of a computer tomography (CT) data collection protocol for determining total body composition used for analysis of tibiotarsal bone quality features. 2. The CT image acquisition was performed on 54 healthy TETRA SL genotype laying hens at 90 weeks of age as well as in the 69th week of the egg production period in vivo and their tibiotarsal bones, ex vivo. 3. Breaking strengths and ash content of the tibiotarsal bones were estimated based on the calculated mineral density of skeletal and tibiotarsal bones by means of CT with an estimation accuracy R2 0.963 and 0.975, respectively. 4. In conclusion, the current investigation demonstrated that the acquisition protocol of CT for total-body composition analysis has a good potential for measuring the mineral status and breaking strength of the reference bone in laying hen. PMID- 29786459 TI - Anatomy of the Attraction Basins: Breaking with the Intuition. AB - Solving combinatorial optimization problems efficiently requires the development of algorithms that consider the specific properties of the problems. In this sense, local search algorithms are designed over a neighborhood structure that partially accounts for these properties. Considering a neighborhood, the space is usually interpreted as a natural landscape, with valleys and mountains. Under this perception, it is commonly believed that, if maximizing, the solutions located in the slopes of the same mountain belong to the same attraction basin, with the peaks of the mountains being the local optima. Unfortunately, this is a widespread erroneous visualization of a combinatorial landscape. Thus, our aim is to clarify this aspect, providing a detailed analysis of, first, the existence of plateaus where the local optima are involved, and second, the properties that define the topology of the attraction basins, picturing a reliable visualization of the landscapes. Some of the features explored in this article have never been examined before. Hence, new findings about the structure of the attraction basins are shown. The study is focused on instances of permutation-based combinatorial optimization problems considering the 2-exchange and the insert neighborhoods. As a consequence of this work, we break away from the extended belief about the anatomy of attraction basins. PMID- 29786458 TI - How to Specify a Reference Point in Hypervolume Calculation for Fair Performance Comparison. AB - The hypervolume indicator has frequently been used for comparing evolutionary multi-objective optimization (EMO) algorithms. A reference point is needed for hypervolume calculation. However, its specification has not been discussed in detail from a viewpoint of fair performance comparison. A slightly worse point than the nadir point is usually used for hypervolume calculation in the EMO community. In this paper, we propose a reference point specification method for fair performance comparison of EMO algorithms. First, we discuss the relation between the reference point specification and the optimal distribution of solutions for hypervolume maximization. It is demonstrated that the optimal distribution of solutions strongly depends on the location of the reference point when a multi-objective problem has an inverted triangular Pareto front. Next, we propose a reference point specification method based on theoretical discussions on the optimal distribution of solutions. The basic idea is to specify the reference point so that a set of well-distributed solutions over the entire linear Pareto front has a large hypervolume and all solutions in such a solution set have similar hypervolume contributions. Then, we examine whether the proposed method can appropriately specify the reference point through computational experiments on various test problems. Finally, we examine the usefulness of the proposed method in a hypervolume-based EMO algorithm. Our discussions and experimental results clearly show that a slightly worse point than the nadir point is not always appropriate for performance comparison of EMO algorithms. PMID- 29786460 TI - Counterexample-Driven Genetic Programming: Heuristic Program Synthesis from Formal Specifications. AB - Conventional genetic programming (GP) can guarantee only that synthesized programs pass tests given by the provided input-output examples. The alternative to such a test-based approach is synthesizing programs by formal specification, typically realized with exact, nonheuristic algorithms. In this article, we build on our earlier study on Counterexample-Based Genetic Programming (CDGP), an evolutionary heuristic that synthesizes programs from formal specifications. The candidate programs in CDGP undergo formal verification with a Satisfiability Modulo Theory (SMT) solver, which results in counterexamples that are subsequently turned into tests and used to calculate fitness. The original CDGP is extended here with a fitness threshold parameter that decides which programs should be verified, a more rigorous mechanism for turning counterexamples into tests, and other conceptual and technical improvements. We apply it to 24 benchmarks representing two domains: the linear integer arithmetic (LIA) and the string manipulation (SLIA) problems, showing that CDGP can reliably synthesize provably correct programs in both domains. We also confront it with two state-of the art exact program synthesis methods and demonstrate that CDGP effectively trades longer synthesis time for smaller program size. PMID- 29786457 TI - Xanthine oxidase inhibitors and sepsis. AB - Xanthine oxidase activation occurs in sepsis and results in the generation of uric acid (UrAc) and reactive oxygen species (ROS). We aimed to evaluate the effect of xanthine oxidase inhibitors (XOis) in rats stimulated with lipopolysaccharide (LPS). LPS (10 mg/kg) was administered intraperitoneally (i.p.) immediately after allopurinol (Alo, 2 mg/kg) or febuxostat (Feb, 1 mg/kg) every 24 h for 3 days. To increase UrAc levels, oxonic acid (Oxo) was administered by gavage (750 mg/kg per day) for 5 days. Animals were divided into the following 10 groups (n = 6 each): (1) Control, (2) Alo, (3) Feb, (4) LPS, (5) LPSAlo, (6) LPSFeb, (7) Oxo, (8) OxoLPS, (9) OxoLPSAlo, and (10) OxoLPSFeb. Feb with or without Oxo did not aggravate sepsis. LPS administration (with or without Oxo) significantly decreased the creatinine clearance (ClCr) in LPSAlo (60%, P < 0.01) versus LPS (44%, P < 0.05) and LPSFeb (35%, P < 0.05). Furthermore, a significant increase in mortality was observed with LPSAlo (28/34, 82%) compared to LPS treatment alone (10/16, 63%) and LPSFeb (11/17, 65%, P < 0.05). In addition, increased levels of thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 were observed at 72 h compared to the groups that received LPS and LPSFeb with or without Oxo. In this study, coadministration of Alo in LPS-induced experimental sepsis aggravated septic shock, leading to mortality, renal function impairment, and high ROS and proinflammatory IL levels. In contrast, administration of Feb did not potentiate sepsis, probably because it did not interfere with other metabolic events. PMID- 29786461 TI - Gender and diagnostic impact on everyday technology use: a differential item functioning (DIF) analysis of the Everyday Technology Use Questionnaire (ETUQ). AB - BACKGROUND: As the use of everyday technology is increasingly important for participation in daily activities, more in-depth knowledge of everyday technology use in relation to diagnosis and gender is needed. The purpose of this study was to investigate the stability of the perceived challenge of a variety of everyday technologies across different samples of varying diagnoses including both males and females. METHODS: This cross-sectional study used 643 data records from clinical and research samples, including persons with dementia or related disorders, acquired brain injury, intellectual disability, various mental or medical disorders, and adults without known diagnoses. The Everyday Technology Use Questionnaire, comprising 93 everyday technology artifacts and services (items) measuring the level of everyday technology challenge and relevance of and perceived ability to use these was used for data gathering. A two-faceted Rasch model in combination with differential item functioning (DIF) analyses were used for comparing item hierarchies across samples. RESULTS: Only three items (3.2%) demonstrated a clinically relevant DIF by gender, and nine items (9.7%) by diagnosis. DISCUSSION: The findings support a stable hierarchy of everyday technology challenge in home and community that can facilitate planning of an accessible and inclusive society from a technological departure point. Implications for Rehabilitation The ability to manage everyday technology is increasingly important for participation in everyday activities at home and in the community for people with and without disabilities. This study demonstrates that differences in perceived challenges in using various everyday technologies across gender and diagnosis are minimal. The findings provide evidence of no or minor systematic bias in testing when using the Everyday Technology Use Questionnaire in clinical practice and research. Empirical knowledge about the perceived challenge of specific everyday technologies of people with variations in gender or diagnosis is still sparse, hence this study can inspire practice and future research. PMID- 29786462 TI - Multi-institutional study of the variability in target delineation for six targets commonly treated with radiosurgery. AB - BACKGROUND: Although accurate delineation of the target is a key factor of success in radiosurgery there are no consensus guidelines for target contouring. AIM: The aim of the present study was therefore to quantify the variability in target delineation and discuss the potential clinical implications, for six targets regarded as common in stereotactic radiosurgery. MATERIAL AND METHODS: Twelve Gamma Knife centers participated in the study by contouring the targets and organs at risks and performing the treatment plans. Analysis of target delineation variability was based on metrics defined based on agreement volumes derived from overlapping structures following a previously developed method. The 50% agreement volume (AV50), the common and the encompassing volumes as well as the Agreement Volume Index (AVI) were determined. RESULTS: Results showed that the lowest AVI (0.16) was found for one of the analyzed metastases (range of delineated volumes 1.27-3.33 cm3). AVI for the other two metastases was 0.62 and 0.37, respectively. Corresponding AVIs for the cavernous sinus meningioma, pituitary adenoma and vestibular schwannoma were 0.22, 0.37 and 0.50. CONCLUSIONS: This study showed that the variability in the contouring was much higher than expected and therefore further work in standardizing the contouring practice in radiosurgery is warranted. PMID- 29786464 TI - What Can Be Learned from Diffusion Tensor Imaging from a Large Traumatic Brain Injury Cohort?: White Matter Integrity and Its Relationship with Outcome. AB - Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI), but its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter (WM) integrity by detecting water molecule diffusion alterations. Therefore, DTI may improve detection and description of TAI lesions after TBI. We have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest (ROI) method was applied to obtain mean fractional anisotropy (FA) value in 28 WM fiber bundles susceptible to TAI. Our main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all ROI measured. We found statistically significant correlation between FA metrics and some demographic, clinical, and conventional imaging characteristics. Additionally, these FA metrics were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. We conclude that FA reduction in the subacute stage after TBI assessed by DTI may be a useful prognostic factor for long-term unfavorable outcome. PMID- 29786463 TI - Hybrid Diffusion Imaging in Mild Traumatic Brain Injury. AB - Mild traumatic brain injury (mTBI) is an important public health problem. Although conventional medical imaging techniques can detect moderate-to-severe injuries, they are relatively insensitive to mTBI. In this study, we used hybrid diffusion imaging (HYDI) to detect white matter alterations in 19 patients with mTBI and 23 other trauma control patients. Within 15 days (standard deviation = 10) of brain injury, all subjects underwent magnetic resonance HYDI and were assessed with a battery of neuropsychological tests of sustained attention, memory, and executive function. Tract-based spatial statistics (TBSS) was used for voxel-wise statistical analyses within the white matter skeleton to study between-group differences in diffusion metrics, within-group correlations between diffusion metrics and clinical outcomes, and between-group interaction effects. The advanced diffusion imaging techniques, including neurite orientation dispersion and density imaging (NODDI) and q-space analyses, appeared to be more sensitive then classic diffusion tensor imaging. Only NODDI-derived intra-axonal volume fraction (Vic) demonstrated significant group differences (i.e., 5-9% lower in the injured brain). Within the mTBI group, Vic and a q-space measure, P0, correlated with 6 of 10 neuropsychological tests, including measures of attention, memory, and executive function. In addition, the direction of correlations differed significantly between groups (R2 > 0.71 and pinteration < 0.03). Specifically, in the control group, higher Vic and P0 were associated with better performances on clinical assessments, whereas in the mTBI group, higher Vic and P0 were associated with worse performances with correlation coefficients >0.83. In summary, the NODDI-derived axonal density index and q-space measure for tissue restriction demonstrated superior sensitivity to white matter changes shortly after mTBI. These techniques hold promise as a neuroimaging biomarker for mTBI. PMID- 29786466 TI - Mineralo-organic nanoparticles in health and disease: an overview of recent findings. AB - We observed earlier that mineralo-organic nanoparticles form in human body fluids when the concentrations of calcium, carbonate and phosphate exceed saturation. The particles have been shown to represent mineral precursors in developing bones and teeth as well as in ectopic calcification and kidney stones. Recent studies suggest that the mineral particles may also be involved in other physiological processes, including immune tolerance against the gut microbiota and food antigens. We review here the involvement of mineralo-organic nanoparticles in physiological and pathological processes and discuss recent findings that reveal novel and unexpected roles for these particles in the human body. PMID- 29786465 TI - Trunk Stability Enabled by Noninvasive Spinal Electrical Stimulation after Spinal Cord Injury. AB - Electrical neuromodulation of spinal networks improves the control of movement of the paralyzed limbs after spinal cord injury (SCI). However, the potential of noninvasive spinal stimulation to facilitate postural trunk control during sitting in humans with SCI has not been investigated. We hypothesized that transcutaneous electrical stimulation of the lumbosacral enlargement can improve trunk posture. Eight participants with non-progressive SCI at C3-T9, American Spinal Injury Association Impairment Scale (AIS) A or C, performed different motor tasks during sitting. Electromyography of the trunk muscles, three dimensional kinematics, and force plate data were acquired. Spinal stimulation improved trunk control during sitting in all tested individuals. Stimulation resulted in elevated activity of the erector spinae, rectus abdominis, and external obliques, contributing to improved trunk control, more natural anterior pelvic tilt and lordotic curve, and greater multi-directional seated stability. During spinal stimulation, the center of pressure (COP) displacements decreased to 1.36 +/- 0.98 mm compared with 4.74 +/- 5.41 mm without stimulation (p = 0.0156) in quiet sitting, and the limits of stable displacement increased by 46.92 +/- 35.66% (p = 0.0156), 36.92 +/- 30.48% (p = 0.0156), 54.67 +/- 77.99% (p = 0.0234), and 22.70 +/- 26.09% (p = 0.0391) in the forward, backward, right, and left directions, respectively. During self-initiated perturbations, the correlation between anteroposterior arm velocity and the COP displacement decreased from r = 0.5821 (p = 0.0007) without to r = 0.5115 (p = 0.0039) with stimulation, indicating improved trunk stability. These data demonstrate that the spinal networks can be modulated transcutaneously with tonic electrical spinal stimulation to physiological states sufficient to generate a more stable, erect sitting posture after chronic paralysis. PMID- 29786467 TI - Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer. AB - AIM: To synthesize and evaluate the imaging potential of Bom-PEG-[64Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. MATERIALS & METHODS: [64Cu]CuS NPs were synthesized in aqueous solution by 64CuCl2 and Na2S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [64Cu]CuS NPs to produce Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. RESULTS: Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[64Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. CONCLUSION: Radiolabeled Bom-PEG-[64Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT. PMID- 29786468 TI - A Course-Embedded Comparison of Instructor-Generated Videos of Either an Instructor Alone or an Instructor and a Student. AB - Instructor-generated videos have become a popular way to engage students with material before a class, yet this is a relatively unexplored area of research. There is support for the use of videos in which instructors tutor students, but few studies have been conducted within the context of a classroom. In this study, conducted in a large-enrollment college physiology course, we used a randomized crossover design to compare the impact of two types of instructor-generated videos that students watched as part of their preclass assignments. We compared videos featuring only an instructor (instructor-only videos) with videos featuring an instructor tutoring a student (instructor-tutee videos). We analyzed student survey responses and weekly physiology quiz scores and found that students preferred, enjoyed, and valued the instructor-only videos significantly more than the instructor-tutee videos. In contrast to prior literature, students with a grade point average (GPA) below the median (3.49) performed significantly better on physiology quizzes after watching instructor-only videos compared with instructor-tutee videos. Students with a GPA at or above the median performed equivalently on physiology quizzes after watching instructor-only or instructor tutee videos. We present this study as an example of bringing cognitive science studies into the context of a real physiology classroom. PMID- 29786469 TI - Estimation versus falsification approaches in sport and exercise science. AB - There has been a recent resurgence in debate about methods for statistical inference in science. The debate addresses statistical concepts and their impact on the value and meaning of analyses' outcomes. In contrast, philosophical underpinnings of approaches and the extent to which analytical tools match philosophical goals of the scientific method have received less attention. This short piece considers application of the scientific method to "what-is-the influence-of x-on-y" type questions characteristic of sport and exercise science. We consider applications and interpretations of estimation versus falsification based statistical approaches and their value in addressing how much x influences y, and in measurement error and method agreement settings. We compare estimation using magnitude based inference (MBI) with falsification using null hypothesis significance testing (NHST), and highlight the limited value both of falsification and NHST to address problems in sport and exercise science. We recommend adopting an estimation approach, expressing the uncertainty of effects of x on y, and their practical/clinical value against pre-determined effect magnitudes using MBI. PMID- 29786470 TI - Direct cortical stimulation of inferior frontal cortex disrupts both speech and music production in highly trained musicians. AB - Music and speech are human-specific behaviours that share numerous properties, including the fine motor skills required to produce them. Given these similarities, previous work has suggested that music and speech may at least partially share neural substrates. To date, much of this work has focused on perception, and has not investigated the neural basis of production, particularly in trained musicians. Here, we report two rare cases of musicians undergoing neurosurgical procedures, where it was possible to directly stimulate the left hemisphere cortex during speech and piano/guitar music production tasks. We found that stimulation to left inferior frontal cortex, including pars opercularis and ventral pre-central gyrus, caused slowing and arrest for both speech and music, and note sequence errors for music. Stimulation to posterior superior temporal cortex only caused production errors during speech. These results demonstrate partially dissociable networks underlying speech and music production, with a shared substrate in frontal regions. PMID- 29786472 TI - High-Speed Fluoroscopy to Measure Dynamic Spinal Cord Deformation in an In Vivo Rat Model. AB - Although spinal cord deformation is thought to be a predictor of injury severity, few researchers have investigated dynamic cord deformation, in vivo, during impact. This is needed to establish correlations among impact parameters, internal cord deformation, and histological and functional outcomes. Relying on surface deformations alone may not sufficiently represent spinal cord deformation. The objective of this study was to develop a high-speed fluoroscopic method of tracking the surface and internal cord deformations of rat spinal cord during experimental cord injury. Two radio-opaque beads were injected into the cord at C5/6 in the dorsal and ventral white matter. Four additional beads were glued to the surface of the cord. Dynamic bead displacement was tracked during a dorsal impact (130 mm/sec, 1 mm depth) by high-speed radiographic imaging at 3000 FPS, laterally. The internal spinal cord beads displaced significantly more than the surface beads in the ventral direction (1.1-1.9 times) and more than most surface beads in the cranial direction (1.2-1.5 times). The dorsal beads (internal and surface) displaced more than the ventral beads during all impacts. The bead displacement pattern implies that the spinal cord undergoes complex internal and surface deformations during impact. Residual displacement of the internal beads was significantly greater than that of the surface beads in the cranial-caudal direction but not the dorsoventral direction. Finite element simulation confirmed that the additional bead mass likely had little effect on the internal cord deformations. These results support the merit of this technique for measuring in vivo spinal cord deformation. PMID- 29786473 TI - Re: "Concurrent Milk Ingestion Decreases Absorption of Levothyroxine" by Chon et al. (Thyroid 2018;28:454-457). PMID- 29786471 TI - The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans. AB - Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents, but human studies are scarce. In a randomized, placebo-controlled study, 25 (10 women) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol (282 mg/d, 80 mg/d, respectively, EGCG+RES, n = 11) or placebo (PLA, n = 14) supplementation for 12 weeks. Abdominal subcutaneous adipose tissue (SAT) biopsies were collected for assessment of adipocyte morphology and micro-array analysis. EGCG+RES had no effects on adipocyte size and distribution compared with PLA. However, we identified pathways contributing to adipogenesis, cell cycle and apoptosis were significantly downregulated by EGCG+RES versus PLA. Furthermore, EGCG+RES significantly decreased expression of pathways related to energy metabolism, oxidative stress, inflammation, and immune defense as compared with PLA. In conclusion, the SAT gene expression profile indicates a reduced cell turnover after 12-week EGCG+RES in overweight-obese subjects. It remains to be elucidated whether these alterations translate into long-term metabolic effects. PMID- 29786474 TI - A Mixed-Methods Investigation of Clicker Implementation Styles in STEM. AB - Active learning with clickers is a common approach in high-enrollment, lecture based courses in science, technology, engineering, and mathematics. In this study, we describe the procedures that faculty at one institution used when implementing clicker-based active learning, and how they situated these activities in their class sessions. Using a mixed-methods approach, we categorized faculty into four implementation styles based on quantitative observation data and conducted qualitative interviews to further understand why faculty used these styles. We found that faculty tended to use similar procedures when implementing a clicker activity, but differed on how they situated the clicker-based active learning into their courses. These variations were attributed to different faculty goals for using clicker-based active learning, with some using it to engage students at specific time points throughout their class sessions and others who selected it as the best way to teach a concept from several possible teaching techniques. Future research should continue to investigate and describe how active-learning strategies from literature may differ from what is being implemented. PMID- 29786475 TI - Connecting Structure-Property and Structure-Function Relationships across the Disciplines of Chemistry and Biology: Exploring Student Perceptions. AB - While many university students take science courses in multiple disciplines, little is known about how they perceive common concepts from different disciplinary perspectives. Structure-property and structure-function relationships have long been considered important explanatory concepts in the disciplines of chemistry and biology, respectively. Fourteen university students concurrently enrolled in introductory chemistry and biology courses were interviewed to explore their perceptions regarding 1) the meaning of structure, properties, and function; 2) the presentation of these concepts in their courses; and 3) how these concepts might be related. Findings suggest that the concepts of structure and properties were interpreted similarly between chemistry and biology, but students more closely associated the discussion of structure property relationships with their chemistry courses and structure-function with biology. Despite receiving little in the way of instructional support, nine students proposed a coherent conceptual relationship, indicating that structure determines properties, which determine function. Furthermore, students described ways in which they connected and benefited from their understanding. Though many students are prepared to make these connections, we would encourage instructors to engage in cross-disciplinary conversations to understand the shared goals and disciplinary distinctions regarding these important concepts in an effort to better support students unable to construct these connections for themselves. PMID- 29786476 TI - Orthopedic Injured versus Uninjured Comparison Groups for Neuroimaging Research in Mild Traumatic Brain Injury. AB - To address controversy surrounding the most appropriate comparison group for mild traumatic brain injury (mTBI) research, mTBI patients 12-30 years of age were compared with an extracranial orthopedic injury (OI) patient group and an uninjured, typically developing (TD) participant group with comparable demographic backgrounds. Injured participants underwent subacute (within 96 h) and late (3 months) diffusion tensor imaging (DTI); TD controls underwent DTI once. Group differences in fractional anisotropy (FA) and mean diffusivity (MD) of commonly studied white matter tracts were assessed. For FA, subacute group differences occurred in the bilateral inferior frontal occipital fasciculus (IFOF) and right inferior longitudinal fasciculus (ILF), and for MD, differences were found in the total corpus callosum, right uncinate fasciculus, IFOF, ILF, and bilateral cingulum bundle (CB). In these analyses, differences (lower FA and higher MD) were generally observed between the mTBI and TD groups but not between the mTBI and OI groups. After a 3 month interval, groups significantly differed in left IFOF FA and in right IFOF and CB MD; the TD group had significantly higher FA and lower MD than both injury groups, which did not differ. There was one exception to this pattern, in which the OI group demonstrated significantly lower FA in the left ILF than the TD group, although neither group differed from the mTBI group. The mTBI and OI groups had generally similar longitudinal results. Findings suggest that different conclusions about group-level DTI analyses could be drawn, depending on the selected comparison group, highlighting the need for additional research in this area. Where possible, mTBI studies may benefit from the inclusion of both OI and TD controls. PMID- 29786477 TI - The impact of a multi-specialty team for high risk pulmonary embolism on resident and fellow education. AB - The impact of the Pulmonary Embolism Response Team (PERT) model on trainee physician education and autonomy over the management of high risk pulmonary embolism (PE) is unknown. A resident and fellow questionnaire was administered 1 year after PERT implementation. A total of 122 physicians were surveyed, and 73 responded. Even after 12 months of interacting with the PERT consultative service, and having formal instruction in high risk PE management, 51% and 49% of respondents underestimated the true 3-month mortality for sub-massive and massive PE, respectively, and 44% were unaware of a common physical exam finding in patients with PE. Comparing before and after PERT implementation, physicians perceived enhanced confidence in identifying ( p<0.001), and managing ( p=0.003) sub-massive/massive PE, enhanced confidence in treating patients appropriately with systemic thrombolysis ( p=0.04), and increased knowledge of indications for systemic thrombolysis and surgical embolectomy ( p=0.043 and p<0.001, respectively). Respondents self-reported an increased fund of knowledge of high risk PE pathophysiology (77%), and the perception that a multi-disciplinary team improves the care of patients with high risk PE (89%). Seventy-one percent of respondents favored broad implementation of a PERT similar to an acute myocardial infarction team. Overall, trainee physicians at a large institution perceived an enhanced educational experience while managing PE following PERT implementation, believing the team concept is better for patient care. PMID- 29786479 TI - Re: "Seasonal Changes in Serum Thyrotropin Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan" by Yoshihara et al. (Thyroid 2018;28:429-436). PMID- 29786480 TI - Four decades of publication: JSCM articles with staying power. PMID- 29786478 TI - Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. PMID- 29786481 TI - Rat Cranial Bone-Derived Mesenchymal Stem Cell Transplantation Promotes Functional Recovery in Ischemic Stroke Model Rats. AB - The functional disorders caused by central nervous system (CNS) diseases, such as ischemic stroke, are clinically incurable and current treatments have limited effects. Previous studies suggested that cell-based therapy using mesenchymal stem cells (MSCs) exerts therapeutic effects for ischemic stroke. In addition, the characteristics of MSCs may depend on their sources. Among the derived tissues of MSCs, we have focused on cranial bones originating from the neural crest. We previously demonstrated that the neurogenic potential of human cranial bone-derived MSCs (cMSCs) was higher than that of human iliac bone-derived MSCs. Therefore, we presumed that cMSCs have a higher therapeutic potential for CNS diseases. However, the therapeutic effects of cMSCs have not yet been elucidated in detail. In the present study, we aimed to demonstrate the therapeutic effects of transplantation with rat cranial bone-derived MSCs (rcMSCs) in ischemic stroke model rats. The mRNA expression of brain-derived neurotrophic factor and nerve growth factor was significantly stronger in rcMSCs than in rat bone marrow derived MSCs (rbMSCs). Ischemic stroke model rats in the rcMSC transplantation group showed better functional recovery than those in the no transplantation and rbMSC transplantation groups. Furthermore, in the in vitro study, the conditioned medium of rcMSCs significantly suppressed the death of neuroblastoma * glioma hybrid cells (NG108-15) exposed to oxidative and inflammatory stresses. These results suggest that cMSCs have potential as a candidate cell-based therapy for CNS diseases. PMID- 29786482 TI - Human Epidermal Growth Factor 2-positive Breast Cancer with Mammographic Microcalcification: Relationship to Pathologic Complete Response after Neoadjuvant Chemotherapy. AB - Purpose To determine the relationship between the presence or absence of mammographic calcifications in human epidermal growth factor receptor 2 (HER2) positive breast cancers and pathologic complete response (pCR) to neoadjuvant chemotherapy and to determine other tumor and clinical characteristics that may be predictive of such a response. Materials and Methods A database of all patients with HER2-positive breast cancer who underwent neoadjuvant chemotherapy between 2007 and 2015 was retrospectively reviewed. Patient demographic characteristics, mammographic appearance, molecular subtype of cancer (luminal or nonluminal), radiologic response (based on breast magnetic resonance images), surgery, and pathologic response to treatment were recorded. Inter- and subgroup comparison was performed for presence of mammographic microcalcification and cancer subtype by using Mann-Whitney and chi2 tests and logistic regression. Results A total of 111 patients with a median age of 49 years (interquartile range, 40-57 years) were evaluated. Of these, 64.9% (72 of 111) had mammographic microcalcifications, 63.1% (70 of 111) had luminal B cancer, and 36.9% (41 of 111) had nonluminal HER2-positive cancer. Radiologic response to neoadjuvant chemotherapy was observed in 70.3% (78 of 111) of patients. Surgery was performed in 97.3% (108 of 111) of patients, and 30.6% (34 of 111) of patients underwent breast conservation. pCR was observed in 33.3% (37 of 111) of patients; 16.2% (18 of 111) showed residual ductal carcinoma in situ and 50.5% (56 of 111) had residual invasive disease. The pCR rate was the same (P = .21) in patients with mammographic microcalcification (29.2% [21 of 72]) as in those without calcification (41.0% [16 of 39]). The pCR rate in patients with nonluminal HER2 positive cancers (46.3% [19 of 41]) was higher (P = .01) than in those with luminal B cancers (25.7% [18 of 70]). pCR was associated with nonluminal HER2 positive subtype (odds ratio, 5.4; 95% confidence interval: 1.8, 16.0; P = .01) and complete radiologic response (odds ratio, 20.4; 95% confidence interval: 3.3, 126.6; P = .01). Conclusion Patients with HER2-positive cancer and mammographic microcalcification can achieve pCR after neoadjuvant chemotherapy. Nonluminal HER2-positive subtype and complete radiologic response are predictors of pCR. PMID- 29786484 TI - Why Is Cognitive Impairment Present in Multiple Sclerosis? Insights from Functional MRI. PMID- 29786483 TI - Immediate Mild Reactions to CT with Iodinated Contrast Media: Strategy of Contrast Media Readministration without Corticosteroids. AB - Purpose To evaluate premedication protocols involving administration of antihistamine and multidose corticosteroid that have been widely used in prevention of recurrent hypersensitivity reactions (HSRs) to iodinated contrast media (ICM); an evidence-based optimal preventive strategy customized for patients with mild cases has not yet been established. Materials and Methods The outcomes of patients with mild HSR who subsequently underwent contrast material enhanced computed tomography (CT) between January 2012 and December 2015 were analyzed. For premedication, 4 mg of chlorpheniramine was intravenously administered 30 minutes prior to reexposure to ICM. Logistic regression with generalized estimating equations was used to determine the relationship between premedication and recurrence rate. Results A total of 1178 patients with mild immediate HSR were reexposed to ICM 3533 times. Among these patients, 1056 patients experienced allergylike reactions and 122 patients developed gastrointestinal reactions. With reexposure to the culprit agent without premedication, the recurrence rate was 31.1% (85 of 273 examinations). The recurrence rate decreased to 12% (105 of 872 examinations; P < .001) by only changing the culprit agent and to 7.6% (148 of 1947 examinations; P < .001) by using the combination of changing the ICM and antihistamine premedication. Changing the ICM plus antihistamine premedication was also helpful in reducing the recurrence of gastrointestinal symptoms from 16.1% to 1.8% (P = .020). However, despite changing of the ICM, some combinations of ICM did not show a prophylactic effect. Conclusion A combination of changing the culprit agent and antihistamine premedication resulted in the best preventive outcome for patients with mild immediate HSR. The optimal choice of substitute ICM could be individualized according to the culprit agent. PMID- 29786485 TI - Organized Chaos: Does PI-RADS Version 2 Work in the Transition Zone? PMID- 29786486 TI - One-year Retention of Gadolinium in the Brain: Comparison of Gadodiamide and Gadoterate Meglumine in a Rodent Model. AB - Purpose To compare the long-term brain elimination kinetics and gadolinium species in healthy rats after repeated injections of the contrast agents gadodiamide (a linear contrast agent) or gadoterate (a macrocyclic contrast agent). Materials and Methods Nine-week-old rats received five doses of 2.4 mmol gadolinium per kilogram of body weight over 5 weeks and were followed for 12 months with T1-weighted MRI (n = 140 rats, corresponding to seven time points, two contrast agents, and 10 rats per group). Animals were sacrificed at 1 week, 1 month, and 2, 3, 4, 5, and 12 months after the last injection. Brain and plasma were sampled to determine the total gadolinium concentration by using inductively coupled plasma mass spectrometry (ICP-MS). For the cerebellum, gadolinium speciation analysis was performed after mild extraction at four time points (1 month and 3, 5, and 12 months after the last injection) by using size exclusion chromatography and hydrophilic interaction liquid chromatography, both coupled to ICP-MS. Tissue gadolinium kinetics were fitted to estimate the area under the curves and tissue elimination half-lives over the 12-month injection-free period. Results T1 hyperintensity of the deep cerebellar nuclei was observed only in gadodiamide-treated rats and remained stable from the 1st month after the last injection (the ratio of the signal intensity of the deep cerebellar nuclei to the signal intensity of the brain stem at 1 year: 1.101 +/- 0.023 vs 1.037 +/- 0.022 before injection, P < .001). Seventy-five percent of the total gadolinium detected after the last injection of gadodiamide (3.25 nmol/g +/- 0.30) was retained in the cerebellum at 1 year (2.45 nmol/g +/- 0.35), with binding of soluble gadolinium to macromolecules. No T1 hyperintensity was observed with gadoterate, consistent with a rapid, time-dependent washout of the intact gadolinium chelate down to background levels (0.07 nmol/g +/- 0.03). Conclusion After repeated administration of gadodiamide, a large portion of gadolinium was retained in the brain, with binding of soluble gadolinium to macromolecules. After repeated injection of gadoterate, only traces of the intact chelated gadolinium were observed with time-dependent clearance. Online supplemental material is available for this article. PMID- 29786488 TI - Gadolinium Deposition in the Brain: We Need to Differentiate between Chelated and Dechelated Gadolinium. PMID- 29786487 TI - Diffusion-weighted MRI Is Superior to PET/CT in Predicting Survival of Patients Undergoing 90Y Radioembolization of Hepatic Metastases. AB - Purpose To determine the relationship between diffusion-weighted (DW) liver MR images obtained 4-6 weeks after lobar yttrium 90 (90Y) treatment and overall survival in comparison with PET/CT or established oncologic factors known to affect survival. Materials and Methods The institutional review board approved this prospective intraindividual comparative study in 36 consecutive patients (25 women) with liver-dominant metastases (20 colorectal, 14 breast, two other) (mean age, 60 years +/- 10 [standard deviation]) who underwent fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT and DW MRI before and 4-6 weeks after 90Y radioembolization. DW MRI response was defined as a mean minimal apparent diffusion coefficient increase of more than 30%; PET/CT response was defined as a mean maximal standardized uptake value decrease of more than 30%. Kaplan-Meier curves, log-rank test, and multivariable Cox regression analyses were used to compare patient survival as a function of imaging and Response Evaluation Criteria in Solid Tumors (RECIST) response, pretreatment Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1), hepatic tumor load (<25% vs >=25%), and presence versus absence of extrahepatic disease. Results Thirty five of the 36 patients were observed until death (median survival, 36 weeks). Response was observed with PET/CT in 18 of 36 patients (50%). Median survival was 39 weeks in patients who responded to PET/CT versus 27 weeks in those who did not (P = .60). Response was observed with DW MRI in 24 of 36 patients (67%). Median survival was 53 weeks in DW MRI responders versus 20 weeks in nonresponders (P = .01). At multivariable analysis, DW MRI response was the only independent predictor of survival (P < .01). Response based on RECIST parameters, ECOG PS, hepatic tumor load, and presence of extrahepatic metastases did not correlate with survival. Conclusion In patients with hepatic metastases undergoing 90Y radioembolization, prediction of response to therapy with DW MRI was superior to that with PET/CT and established oncologic factors. PMID- 29786489 TI - Determinants of Cognitive Impairment in Patients with Multiple Sclerosis with and without Atrophy. AB - Purpose To investigate the discrepancy between patients with multiple sclerosis (MS) without atrophy who have already developed cognitive impairment and patients with MS with atrophy who have preserved cognitive function. Materials and Methods This retrospective imaging study, with imaging acquired between 2008 and 2012, included 332 patients with MS (106 men and 226 women; mean age, 48.1 years; range, 23.0-72.5 years) and 96 healthy control participants. Cognitive impairment was defined as cognitive performance of z less than -1.5 compared with that in control participants in greater than or equal to two cognitive domains. Atrophy was defined as cortical and deep gray matter volumes of z less than -1.5 compared with that in control participants. White matter lesions were assessed with T2 imaging, tract fractional anisotropy (ie, integrity) with diffusion MRI, and regional centrality (ie, importance within network) with functional MRI. Within each atrophy group, patients with cognitive impairment and preserved cognitive function were compared and regression analyses were performed to predict cognitive impairment. Results A total of 132 of 328 patients with MS had no atrophy; of these, 42 of 132 (32%) had cognitive impairment. Cognitive impairment in patients without atrophy was predicted by level of education (Wald test, 11.63; P < .01) and posterior cingulate centrality (Wald test, 6.82; P < .01). A total of 65 of 328 patients with MS had atrophy; of these, 49 of 65 (75%) had cognitive impairment. Cognitive impairment in patients with atrophy was predicted by white matter tract fractional anisotropy (Wald test, 4.89; P = .03) and posterior cingulate centrality (Wald test, 7.19; P < .01). Conclusion Cognitive impairment was related to white matter damage, but only in patients with MS with atrophy. In patients without atrophy, a lower level of education was most important for cognitive impairment. Posterior cingulate cortex showed functional abnormalities in all MS groups with cognitive impairment, regardless of atrophy. PMID- 29786490 TI - Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. AB - Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi +/- 0.7 (151.7 MBq +/- 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection. PMID- 29786491 TI - Validation of PI-RADS Version 2 in Transition Zone Lesions for the Detection of Prostate Cancer. AB - Purpose To determine the association between Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores and prostate cancer (PCa) in a cohort of patients undergoing biopsy of transition zone (TZ) lesions. Materials and Methods A total of 634 TZ lesions in 457 patients were identified from a prospectively maintained database of consecutive patients undergoing prostate magnetic resonance imaging. Prostate lesions were retrospectively categorized with the PI RADS version 2 system by two readers in consensus who were blinded to histopathologic findings. The proportion of cancer detection for all PCa and for clinically important PCa (Gleason score >=3+4) for each PI-RADS version 2 category was determined. The performance of PI-RADS version 2 in cancer detection was evaluated. Results For PI-RADS category 2 lesions, the overall proportion of cancers was 4% (one of 25), without any clinically important cancer. For PI-RADS category 3, 4, and 5 lesions, the overall proportion of cancers was 22.2% (78 of 352), 39.1% (43 of 110), and 87.8% (129 of 147), respectively, and the proportion of clinically important cancers was 11.1% (39 of 352), 29.1% (32 of 110), and 77.6% (114 of 147), respectively. Higher PI-RADS version 2 scores were associated with increasing likelihood of the presence of clinically important PCa (P < .001). Differences were found in the percentage of cancers in the PI-RADS category between PI-RADS 3 and those upgraded to PI-RADS 4 based on diffusion weighted imaging for clinically important cancers (proportion for clinically important cancers for PI-RADS 3 and PI-RADS 3+1 were 11.1% [39 of 352] and 30.8% [28 of 91], respectively; P < .001). Conclusion Higher PI-RADS version 2 scores are associated with a higher proportion of clinically important cancers in the TZ. PI-RADS category 2 lesions rarely yield PCa, and their presence does not justify targeted biopsy. PMID- 29786494 TI - Failure to tackle suicide inequalities across Europe. AB - SummaryIn this issue, Lorant et al. confirm a social gradient in risk of suicide, across 15 European countries, over a period of marked social change. Understanding contextual and life-course factors, and acknowledging under-funding for mental health and failures to implement national mental health policies, may provide the reasons for these disparities.Declaration of interestNone. PMID- 29786495 TI - Occupational moral injury and mental health: systematic review and meta-analysis. AB - BACKGROUND: Many people confront potentially morally injurious experiences (PMIEs) in the course of their work which can violate deeply held moral values or beliefs, putting them at risk for psychological difficulties (e.g. post-traumatic stress disorder (PTSD), depression, etc.).AimsWe aimed to assess the effect of moral injury on mental health outcomes. METHOD: We conducted a systematic review and meta-analysis to assess the association between work-related PMIEs and mental health disorders. Studies were independently assessed for methodological quality and potential moderator variables, including participant age, gender and PMIE factors, were also examined. RESULTS: Thirteen studies were included, representing 6373 participants. PMIEs accounted for 9.4% of the variance in PTSD, 5.2% of the variance in depression and 2.0% of the variance in suicidality. PMIEs were associated with more symptoms of anxiety and behavioural problems (e.g. hostility), although this relationship was not consistently significant. Moderator analyses indicated that methodological factors (e.g. PMIE measurement tool), demographic characteristics and PMIE variables (e.g. military v. non military context) did not affect the association between a PMIE and mental health outcomes. CONCLUSIONS: Most studies examined occupational PMIEs in military samples and additional studies investigating the effect of PMIEs on civilians are needed. Given the limited number of high-quality studies available, only tentative conclusions about the association between exposure to PMIEs and mental health disorders can be made.Declaration of interestNone. PMID- 29786492 TI - Socioeconomic inequalities in suicide in Europe: the widening gap. AB - BACKGROUND: Suicide has been decreasing over the past decade. However, we do not know whether socioeconomic inequality in suicide has been decreasing as well.AimsWe assessed recent trends in socioeconomic inequalities in suicide in 15 European populations. METHOD: The DEMETRIQ study collected and harmonised register-based data on suicide mortality follow-up of population censuses, from 1991 and 2001, in European populations aged 35-79. Absolute and relative inequalities of suicide according to education were computed on more than 300 million person-years. RESULTS: In the 1990s, people in the lowest educational group had 1.82 times more suicides than those in the highest group. In the 2000s, this ratio increased to 2.12. Among men, absolute and relative inequalities were substantial in both periods and generally did not decrease over time, whereas among women inequalities were absent in the first period and emerged in the second. CONCLUSIONS: The World Health Organization (WHO) plan for 'Fair opportunity of mental wellbeing' is not likely to be met.Declaration of interestNone. PMID- 29786496 TI - On moral psychiatry. PMID- 29786497 TI - Massilia armeniaca sp. nov., isolated from desert soil. AB - A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, strain ZMN-3T, was isolated from desert soil sample collected from Ongniod Qi, Inner Mongolia, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZMN-3T was affiliated with the genus Massilia and showed the highest similarity to Massilia humi THG S6-8T (98.9 %) and Massilia buxea A9T (98.2 %). In partial gyrB and lepA sequences, the highest similarity of strain ZMN-3T and M. humi THG S6-8T were 95.9 and 96.8 %, respectively. The DNA-DNA hybridization value between strain ZMN-3T and its closely related type strains were all below 70 %. The major respiratory quinone of strain ZMN-3T was Q-8 and the major cellular fatty acids consisted of summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 0. The predominant polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content of strain ZMN-3T was 66.3 mol%. On the basis of this polyphasic taxonomic study, strain ZMN-3T is considered to represent a novel species of the genus Massilia, for which the name Massilia armeniaca sp. nov. is proposed. The type strain is ZMN-3T (=CGMCC 1.16209T=DSM 104676T). PMID- 29786498 TI - HCoV-229E spike protein fusion activation by trypsin-like serine proteases is mediated by proteolytic processing in the S2' region. AB - Human coronavirus 229E (HCoV-229E) is responsible for common colds. Like other coronaviruses, HCoV-229E exploits cellular proteases to activate fusion mediated by the spike protein. We analysed the proteolytic processing of the HCoV-229E spike protein by trypsin-like serine proteases leading to activation of the fusion process. Unlike in other coronaviruses, HCoV-229E fusion activation appears to be a one-step process. Indeed, cleavage of the S1/S2 interface does not seem to be a prerequisite, and the fusion activation is highly reliant on the S2' region, with arginine residue 683 acting as the recognition site. PMID- 29786500 TI - Exploratory Cluster Analysis to Identify Patterns of Chronic Kidney Disease in the 500 Cities Project. AB - Chronic kidney disease is a leading cause of death in the United States. We used cluster analysis to explore patterns of chronic kidney disease in 500 of the largest US cities. After adjusting for socio-demographic characteristics, we found that unhealthy behaviors, prevention measures, and health outcomes related to chronic kidney disease differ between cities in Utah and those in the rest of the United States. Cluster analysis can be useful for identifying geographic regions that may have important policy implications for preventing chronic kidney disease. PMID- 29786499 TI - Scheffersomyces stambukii f.a., sp. nov., a d-xylose-fermenting species isolated from rotting wood. AB - Two isolates representing a new species of Scheffersomyces were isolated from rotting wood samples collected in an Amazonian forest ecosystem in Brazil. Analysis of the sequences of the D1/D2 domains showed that this new species is phylogenetically related to Scheffersomyces NYMU 15730, a species without a formal description, and the two are in an early emerging position with respect to the xylose-fermenting subclade containing Scheffersomyces titanus and Scheffersomyces stipitis. Phylogenomic analyses using 474 orthologous genes placed the new species in an intermediary position between Scheffersomyces species and the larger genus Spathaspora and the Candida albicans/Lodderomyces clade. The novel species, Scheffersomyces stambukii f.a., sp. nov., is proposed to accommodate these isolates. The type strain of Scheffersomyces stambukii sp. nov. is UFMG-CM-Y427T (=CBS 14217T). The MycoBank number is MB 824093. In addition, we studied the xylose metabolism of this new species. PMID- 29786501 TI - Strategies to Increase Filipino American Participation in Cardiovascular Health Promotion: A Systematic Review. AB - INTRODUCTION: Cultural tailoring of interventions can be effective in reducing health disparities by attracting underserved populations to health promotion programs and improving their outcomes. The purpose of this systematic review was to assess what is known about increasing access to and participation in cardiovascular disease (CVD) prevention and control programs among Filipino Americans. METHODS: PubMed MEDLINE, CINAHL, and Sociologic Abstracts were searched for peer-reviewed studies and dissertations conducted in the United States from 2004 through 2016. RESULTS: A total of 347 articles were identified through the search, and 9 articles reporting on 7 interventions focused on CVD prevention in a Filipino American sample were included. All but one intervention used evidence-based curricula, and implementation varied across sites. All but 2 interventions used word-of-mouth advertising from friends, family, and community leaders to increase participation. The Filipino cultural values of food, social relationships, and family were prevalent aspects across interventions tailored for Filipino Americans. Aspects of spirituality and the arts were integrated into only 3 studies. CONCLUSION: Given the burden of CVD in Filipino American populations, tailored interventions rooted in Filipino cultural values are vital to address this known health disparity. PMID- 29786502 TI - Best Practices for Financial Sustainability of Healthy Food Service Guidelines in Hospital Cafeterias. AB - In February and March 2017 we examined barriers and facilitators to financial sustainability of healthy food service guidelines and synthesized best practices for financial sustainability in retail operations. We conducted qualitative, in depth interviews with 8 hospital food service directors to learn more about barriers and facilitators to financial sustainability of healthy food service guidelines in retail food service operations. Analysts organized themes around headers in the interview guide and also made note of emerging themes not in the original guide. They used the code occurrence and co-occurrence features in Dedoose version 7.0.23 (SocioCultural Research Consultants) independently to analyze patterns across the interviews and to pull illustrative quotes for analysis. Two overarching themes emerged, related to 1) the demand for and sales of healthy foods and beverages, and 2) the production and supply of healthy foods and beverages. Our study provides insights into how hospital food service directors can maximize revenue and remain financially viable while selling healthier options in on-site dining facilities. PMID- 29786503 TI - Relationships Between Theoretically Derived Short-Term Outcomes and Support for Policy Among the Public and Decision-Makers. AB - PURPOSE AND OBJECTIVES: Policy change is a lengthy and complex process. Thus, it is important to articulate hypothesized causal pathways between advocacy activities and policy change outcomes and to identify and monitor early indicators of progress toward policy change. INTERVENTION APPROACH: The Kansas Health Foundation supports grantee efforts to address the public health effects of obesity through evidence-based policy, systems, and environmental change interventions. To build support for policy, systems, and environmental changes in schools, workplaces, and health care and retail settings, grantees mobilize communities, educate government policy makers, and advocate with organizational decision makers. EVALUATION METHODS: To understand whether early outcomes from obesity-prevention advocacy efforts predict interim outcomes related to eventual policy change, we conducted surveys of the general public and of opinion leaders in Kansas, which were designed to measure components of Kansas Health Foundation's theory of change. We then used structural equation modeling to test the theory of change's underlying relationships by using support for obesity prevention policies as the outcome. RESULTS: Our findings supported the hypothesized model: perceptions of obesity as a serious community problem influence beliefs about causes of the problem. Beliefs about causes predict beliefs about who is responsible for the solution to the problem, which in turn predicts support for obesity prevention policies. IMPLICATIONS FOR PUBLIC HEALTH: Evaluators of advocacy for policy change interventions can use this approach to monitor proximal changes in public and opinion leader beliefs related to eventual policy change and to determine whether efforts are likely to be successful or need to be adapted or abandoned. PMID- 29786504 TI - Transgenic pigs to the rescue. AB - Genetically engineered pigs that digest their food better could help to reduce phosphorus and nitrogen pollution. PMID- 29786505 TI - Can Pallars i Llobateres: A new hominoid-bearing locality from the late Miocene of the Valles-Penedes Basin (NE Iberian Peninsula). AB - In the Iberian Peninsula, Miocene apes (Hominoidea) are generally rare and mostly restricted to the Valles-Penedes Basin. Here we report a new hominoid maxillary fragment with M2 from this basin. It was surface-collected in March 2017 from the site of Can Pallars i Llobateres (CPL, Sant Quirze del Valles), where fossil apes had not been previously recorded. The locality of provenance (CPL-M), which has delivered no further fossil remains, is located very close (ca. 50 m) to previously known CPL outcrops, and not very far (ca. 500 m in NW direction) from the classical hominoid-bearing locality of Can Poncic 1. Here we describe the new fossil and, based on the size and proportions of the M2, justify its taxonomic attribution to Hispanopithecus cf. laietanus, a species previously recorded from several Vallesian sites of the Valles-Penedes Basin. Based on the associated mammalian fauna from CPL, we also provide a biochronological dating and a paleoenvironmental reconstruction for the site. The associated fauna enables an unambiguous correlation to the Cricetulodon hartenbergeri - Progonomys hispanicus interval local subzone, with an estimated age of 9.98-9.73 Ma (late Vallesian, MN10). Therefore, CPL-M is roughly coeval with the Hispanopithecus laietanus bearing localities of Can Llobateres 1 and Can Feu 1, and minimally older than those of La Tarumba 1 and Can Llobateres 2. In contrast, CPL-M is younger than the early Vallesian (MN9) localities of Can Poncic 1 (the type locality of Hispanopithecus crusafonti) as well as Polinya 2 (Gabarro) and Estacio Depuradora d'Aigues Residuals-Riu Ripoll 13, where Hispanopithecus sp. is recorded. The associated fauna from CPL indicates a densely forested and humid paleoenvironment with nearby freshwater. This supports the view that Hispanopithecus might have been restricted to dense wetland forests soon before its extinction during the late Vallesian, due to progressive climatic deterioration. Coupled with the existence of other fossiliferous outcrops in the area, this find is most promising for the prospect of discovering additional fossil hominoid remains in the future. PMID- 29786506 TI - Wing morphogenesis in Lepidoptera. AB - The wings of Lepidoptera develop from imaginal disks that are made up of a simple two-layered epithelium whose structure is always congruent with the final adult wing. It is therefore possible to map every point on the imaginal disk to a location on the adult wing throughout the period of growth and morphogenesis. The wings of different species of Lepidoptera differ greatly in both size and shape, yet it is possible to fate-map homologous locations on the developing wing disks and explicitly monitor the growth, size, and shape of the wing, or any of its regions, throughout the entire ontogeny of the wing. The wing achieves its final form through spatially patterned cell divisions, oriented cell divisions, physical constraints on directional growth by an actin network between the wing veins, and by patterned cell death. Each of these factors contributes differently to morphogenesis and to the development of species-specific differences in wing shape. The final shape of the wing is sculpted out of the much larger imaginal disk by a pattern of programmed cell death that removes all cells distal to the bordering lacuna, and is responsible for the detailed outline of the wing. PMID- 29786507 TI - Severe acute hepatitis after thymoglobulin induction before islet transplantation. PMID- 29786508 TI - [Use of the EvalObs(r) adherence scale in an unselected French population of treated subjects with antihypertensive, hypolipemiants or oral antidiabetics medications: The FLAHS 2017 adherence survey]. AB - OBJECTIVE: A Visual Analog Scale (VAS) is useful for diagnosing medication nonadherence and its validity has been evaluated using electronic pillbox as the gold standard. We have developed the EvaLobs(r) scale for use on paper or on smartphone and the aim of the study was to administrate the scale among FLAHS 2017 participants treated for an hypertension, a dyslipidemia or diabetes. In subjects treated with antihypertensive medications, participants completed the 6 item Girerd Scale and EvaLobs(r). METHODS: The French League Against Hypertension Survey (FLAHS) are carried out by self-questionnaire sent by mail to individuals from the French Kantar Health sampling frame (representative panel of the population living in metropolitan France). In 2017, FLAHS was conducted in 4783 subjects aged 35 and over. The EvaLobs(r) has a scale from 0 to 15 and the use instruction is "how many days have you taken the drug in the past 15 days". A score>12 indicates a "good compliance". The 6-item Girerd scale was also completed. "Good adherence" was determined for a score of 0 to 2 and "nonadherence" for a score of 3 or more. The agreement between EvaLobs(r) and the 6-item Girerd scale was evaluated in treated hypertensives. RESULTS: The survey included 4783 subjects with 1308 treated hypertensives, 942 subjects treated with lipid-lowering drugs and 405 subjects treated with anti-diabetics. EVALOBS(r) indicates "Good adherence" in 96% of subjects and the 6 questions questionnaire indicates "good adherence" in 95% of subjects. An excellent agreement is noted in 93.8%. An EvaLobs(r) score indicating nonadherence or an absence of response to EvaLobs(r) is observed in 3.6% [CI 95, 2.5-4.7] of hypertensives, in 6.0% [CI 95, 3.9-8.1] of diabetics and in 8.2% [CI 95, 6.5-9.9] of dyslipidemic patients. CONCLUSION: In the population living in France and in unselected patients treated for metabolic disease or hypertension, non-adherence is lowest for antihypertensive medications and highest for statins. EvaLobs(r), which shows good agreement with an adherence questionnaire, is a quick and simple tool for assessing adherence. The smartphone app EvaLobs(r) is available for free on Google play and the Apple store. PMID- 29786509 TI - [Targeted screening for pre-eclampsia in the first trimester of pregnancy at Toulouse University Hospital]. AB - GOALS: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality. Early treatment by aspirin has been shown to significantly reduce PE risk before 37weeks supporting the implementation of first-trimester screening. SUBJECTS AND METHODS: A targeted screening was recently implemented at Toulouse University Hospital for women in their first pregnancy or those with personal or familial history of PE. It uses Fetal Medicine Foundation (FMF) algorithm that combines maternal characteristics, clinical, biophysical and biochemical (PAPP-A, Pregnancy Associated Plasma Protein-A, and PlGF, Placental Growth Factor) data. We describe this first population of pregnant women and compare our results with those of a mini-test that excludes PlGF and biophysical data. RESULTS: Between October 2016 and September 2017, 500women have benefited from this screening. In such targeted population, we identified 3,6 % (n=18) of women at high risk to develop PE before 34weeks and 9,6 % (n=48) of women at high risk to develop PE between 34 and 37weeks. When we recalculated the risk using the mini-test, only 10women (56 %) were identified at high risk of early PE. CONCLUSION: For the first time in France, we report the result of a targeted screening of PE during the first trimester using the FMF algorithm. We describe the screened population and show that it is more efficient than the mini-test. PMID- 29786510 TI - Biochemical markers of hypertension, prehypertension. AB - OBJECTIVE: There are insufficient researches aimed at evaluating biochemical markers of mechanisms of formation of AH and lesion of target organs in hypertension and prehypertension. The aim of that research was to study the level of endothelial dysfunction markers and damage to the cardiovascular system in hypertension and prehypertension. PATIENTS AND METHODS: A cross-sectional study was performed among 938 people aged 18 to 65 years. All respondents were surveyed, blood pressure measured, for glucose, cholesterol, interleukin-6, sFAS, LIGHT, hFABP, NT-ProBNP and an Endocan concentrations were tested. Depending on the level of blood pressure participants were splitted into groups with normotension, prehypertension and hypertension. RESULTS: Comparing the markers of inflammation, apoptosis and target organ damage in the prehypertensive group, the level of the LIGHT protein was Me=265.2pg/ml (Q25-Q75: 197.7-444.3), in the control group - Me=251.1pg/ml (Q25-Q75: 176.6-376.6), the Endocan level was Me=660.6pg/ml (Q25-Q75: 419.6-867.4) and in the control group Me=587.5pg/ml (Q25 Q75: 401.9-838.1). In the AH group, the level of the LIGHT Me=273.1pg/ml (Q25 Q75: 195.1-455.2), Endocan Me=668.2pg/ml (Q25-Q75: 434.8-977.3), heart-type fatty acid-binding protein Me=2233.1pg/ml (Q25-Q75: 1518.4-3391.1) exceeded the control group. CONCLUSION: Thus, the development of prehypertension and hypertension is characterized by an increase in the activity of biochemical markers of endothelial dysfunction and damage to target organs, more expressed in the presence of hypertension. PMID- 29786511 TI - [Preeclampsia: A challenge also for cardiologists]. AB - Due to its short-term consequences on perinatal outcome, preeclampsia has been long regarded as an obstetrical disease, strictly confined to a management by OB/GYNs. It has been now widely accepted that preeclampsia is most a systemic inflammatory and systemic vascular disease during pregnancy and then a lifelong risk factor for subsequent cardiovascular event in women's life. The aim of this review is to propose an overview in the current state-of-art in definition, early identification and management of preeclampsia. We will also discuss the growing evidence that support that cardiologists must be fully involved in screening and prevention of preeclampsia during pregnancy and beyond in the subsequent medical follow-up of women who have experienced a preeclampsia. PMID- 29786512 TI - [Kidney full of stones, and an adrenal gland not quite normal]. AB - A 31-year-old patient was followed for cystinuria, justifying CT scans. In 2006, a tissue mass of 3cm of the right adrenal gland, homogeneous, measured at 3.5cm in 2007 was noted. Blood pressure was 90/61mmHg, without orthostatic hypotension. During the clinical interview, no discomfort, sweat attack, headache, or palpitation was reported by the patient. Hormonal assays did not favor a primary hyperaldosteronism, or a hypercortisolism. Adrenal androgens were normal. 24h normetanephrines urinary excretion and metanephrines to creatinine ratio were elevated. One year later, the patient remained asymptomatic and normotensive. Plasma levels of normetanephrine and metanephrine were increased and highly pathological. The tumor was 5cm long and fixed individually on MIBG scintigraphy and PET scan. Right adrenalectomy was performed. A pheochromocytoma was confirmed histologically. The peculiarity here was the absence of symptoms, especially arterial hypertension. This currently affects up to 47% of cases, particularly in the context of incidentaloma investigations and family screening. Indeed, 35 to 40% of pheochromocytomas are associated with a germline mutation, justifying a genetic analysis in this patient. Genetic analysis did not show any mutation associated with pheochromocytoma. At a 6-year interval pheochromocytoma did not reappeared while BP increased reaching hypertension threshold. The only documented recurrence was lithiasis. PMID- 29786513 TI - Randomized clinical trials and personalized medicine: A commentary on deaton and cartwright. PMID- 29786514 TI - Psychotherapy for PTSD: An evidence-based guide to a theranostic approach to treatment. AB - Posttraumatic stress disorder (PTSD) is often a clinically complex disorder, frequently presenting with comorbid clinical conditions. Individuals with PTSD may also present with high-risk symptoms such as substance misuse and suicidal ideation. The clinical complexity of PTSD has precluded some clinicians from providing gold-standard trauma-focused treatment due to concern of iatrogenic effects. However, evidence to date suggests that trauma-focused treatments are safe and effective for PTSD even when higher-risk comorbidity presents. Occasionally, while some patients present with clinical concerns that may benefit from modifications to standard recommended treatment protocols, research suggests there are few absolute contraindications to trauma-focused treatment. The present manuscript provides a review of evidence-based assessment and treatment recommendations for PTSD. A clinical decision-making guide for PTSD across areas of clinical complexity is provided. PMID- 29786515 TI - Research brief: Persistent social inequality in medicine use for headache among adolescents in Denmark 1991-2014. AB - BACKGROUND: Socioeconomic variation in adolescents' medicine use behaviour is an understudied issue. OBJECTIVES: To examine the association between socioeconomic background and medicine use for headache among adolescents, and how this association changes over time. METHODS: Data stem from the Danish part of the international Health Behaviour in School-aged Children (HBSC) study 1991-2014 with data about parents' occupational social class (OSC) and self-reported medicine use for headache, n = 26,685. This study examined absolute social inequality (percent difference between high and low OSC) and relative social inequality (odds ratio for medicine use by OSC). RESULTS: In total, 40.5% used medicine for headache in the past month. There was a significant increase from 32.3% in 1991 to 42.8% in 2002 (test for trend, p < 0.0001) and very little change 2002-2014. This pattern was similar in high, middle and low OSC. The prevalence of medicine use for headache in high, middle and low OSC was 36.2%, 41.5% and 44.8% (p < 0.0001). The OR (95% CI) for medicine use was 1.25 (1.18 1.324) in middle and 1.43 (1.33-1.54) in low OSC. CONCLUSIONS: Medicine use for headache increased 1991-2002 and remained stable 2002-2014. There was increasing medicine use for headache with decreasing OSC; this social inequality was persistent 1991-2014. PMID- 29786516 TI - Immediate or deferred adjustment of drug regimens in multidose drug dispensing systems. AB - BACKGROUND: Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system. OBJECTIVE: The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments. METHODS: This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist. RESULTS: Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p < 0.001). CONCLUSIONS: This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated. PMID- 29786517 TI - Estrogen receptor beta: Potential target for therapy in adult granulosa cell tumors? AB - OBJECTIVE: Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments. METHODS: We evaluated by immunohistochemistry the expression of ERalpha, ERbeta isoforms (i.e. ERbeta1, ERbeta2 and ERbeta5), progesterone and androgen receptor (PR, AR) in 20 untreated AGCTs and 12 unmatched recurrent lesions. Thereafter, we visualized by immunofluorescence, the subcellular distribution of cytoplasmic receptors, and by the proximity ligation assays (PLA) we characterized in situ their ability to interact with other proteins involved in the apoptotic cascade. RESULTS: Primary AGCTs predominantly expressed ERbeta isoforms, along with PR and AR, while only 30% of patients showed ERalpha expression. Recurrent tumors were associated with a decrease in AR levels. From mechanistic studies it emerges that ERbeta2, and to a lesser extent ERbeta1 and AR, are mitochondrial components in cancer cells and that ERbeta2 can act as a binding partner of proteins involved in the apoptotic cascade, in turn potentially inhibiting apoptosis. CONCLUSIONS: As in other endocrine tumors, ERbeta may play a role in the pathogenesis of AGCT; it is crucial to understand estrogen receptor-mediated pathways before planning hormonal treatment strategies in AGCT. PMID- 29786518 TI - Evaluation of serum IgE in peach-allergic patients with systemic reaction by using recombinant Pru p 7 (gibberellin-regulated protein). AB - BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). RESULTS: Peach-allergic patients (n=27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n=17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P<0.05). CONCLUSIONS: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction. PMID- 29786519 TI - Effect of vaccination on cattle subclinically infected with foot-and-mouth disease virus in Cameroon. AB - Foot-and-mouth disease (FMD) is one of the most contagious and economically important livestock diseases worldwide. Four serotypes of FMD virus (FMDV; O, A, SAT1, SAT2) circulate in Cameroon, and a trivalent inactivated vaccine against the three most common serotypes (O, A, SAT2) was recently introduced in 2014. The objective of this study was to characterize vaccine performance in cattle under natural hyperendemic conditions in the Adamawa region of Cameroon. Vaccinated cattle (n = 50) and non-vaccinated controls (n = 100) were monitored by serum and oropharyngeal fluid (OPF) sample collection through a 12-month period. Anti-FMDV non-structural protein (anti-NSP) seroprevalence increased from 59.3% (89/150) at the beginning of the study to 85.8% (103/120) at the end of the study, and FMDV RNA was found in 28% (42/150) of animals overall, despite detection of clinical signs of FMD in only 6 non-vaccinated animals. Viral sequence analysis indicated that subclinical infections of FMDV serotypes O and A were present within the study herds during the study period, which was reflected by an overall increase of anti-NSP seroprevalence during the study. There was no association between vaccination status and seroconversion or prevalence of FMDV RNA in OPF. Younger cattle had higher odds of detection of FMDV RNA in OPF, but older animals were more likely to be seropositive. This study suggests vaccination of herds previously exposed to FMDV may help to limit clinical signs and reduce economic losses caused by FMDV. These findings also suggest that subclinical circulation of FMDV occurs in hyperendemic regions regardless of vaccination. PMID- 29786520 TI - Impact of piglet oral vaccination against tuberculosis in endemic free-ranging wild boar populations. AB - The Eurasian wild boar (Sus scrofa) is the main wild reservoir of the Mycobacterium tuberculosis complex in Mediterranean woodlands and a key risk factor for cattle tuberculosis (TB) breakdowns. Wild boar vaccination therefore has the potential to be a valuable tool for TB control. We tested two orally delivered vaccines, heat-inactivated Mycobacterium bovis (IV) and BCG, in four sites (two per vaccine type: one Managed and one Natural or unmanaged) during four years. TB was also monitored in 15 unvaccinated sites (spatial control), as well as in all sites from one year prior to intervention (temporal control). The rationale is that by vaccinating 2-6 month old wild boar piglets we can reduce disease at the population level during the study period. This is achievable due to the fast turnover of wild boar populations. Vaccine baits were deployed using selective piglet feeders and this method proved highly successful with uptake rates of 50 to 74% in Natural sites and 89 to 92% in Managed sites. This is relevant for the potential delivery of vaccines to control other diseases, too. Local wild boar TB prevalence at the beginning of the study was already high ranging from 50 to 100%. TB prevalence increased in unvaccinated sites (6%), while a significant decline occurred in the Managed IV site (34%). Changes recorded in the remaining sites were not significant. The short-term impact of vaccination observed in the field was complemented by mathematical modelling, representative of the field system, which examined the long-term impact and showed that vaccination of piglets reduced prevalence and increased abundance at the population level. We conclude that IV could become part of integrated TB control schemes, although its application must be tailored for each specific site. PMID- 29786521 TI - Mortality, diarrhea and respiratory disease in Danish dairy heifer calves: Effect of production system and season. AB - Diarrhea and respiratory disease are major health problems for dairy calves, often causing calf mortality. Previous studies have found calf mortality to be higher in organic dairy herds compared to conventional herds. The aim of this study was to investigate the association between production system (conventional/organic), season (summer/winter) and calf mortality risk, diarrhea, signs of respiratory disease and ocular discharge, respectively, for dairy heifer calves aged 0-180 days. Sixty Danish dairy herds, 30 conventional and 30 organic, were visited once during summer and once during winter. During the herd visits, calves were clinically examined for signs of diarrhea, hampered respiration, nasal discharge, coughing and ocular discharge. Data on mortality were obtained from the Danish Cattle Database. Data were analyzed using logistic regression models, with mortality risk and disease measures as outcome variables for each of three calf age groups: 0-28, 29-90 and 91-180 days. In organic herds, odds of mortality among calves aged 0-28 days were 2.09 (95% confidence interval (CI): 1.38-3.15) times higher during winter compared to summer. Odds of nasal discharge for calves 0-28 days in organic herds were 10.3 (95% CI: 2.27-46.6), 10.7 (95% CI: 2.40-40.0) and 5.97 (95% CI: 1.29-27.6) times higher for organic and conventional herds during winter (OW and CW) and conventional herds during summer (CS) respectively, compared to organic herds during summer (OS). For calves aged 29-90 days, odds of nasal discharge were 8.22 (95% CI: 3.88-17.4), 8.06 (95% CI: 3.18-20.4) and 2.86 (95% CI: 1.08-7.55) times higher for OW, CW and CS respectively, compared to OS. Odds of nasal discharge for calved aged 91-180 days were 7.03 (95% CI: 3.95-12.5) and 4.27 (95% CI: 1.81-10.1) times higher for OW and CW respectively compared to OS. For calves aged 29-90 days, odds of coughing were 2.23 (95% CI: 1.06-4.71) and 3.82 (95% CI: 1.76-8.21) times higher for OW and CW compared to OS, while odds of coughing for calves aged 91-180 days were 2.09 (95% CI: 1.19-3.67) and 2.55 (95% CI: 1.39.4.67) times higher for OW and CW compared to OS. Odds of ocular discharge for calves aged 29-90 days were 0.22 (95% CI: 0.10-0.52), 0.27 (95% CI: 0.11-0.66) and 0.42 (95% CI: 0.18-0.99) times higher for OW, CW and CS compared to OS. In conclusion, mortality and morbidity of Danish dairy heifer calves are, for some variables and in certain age groups, dependent on production system and season. PMID- 29786523 TI - Decision support beyond total savings-Eligibility and potential savings for individual participants from changes in the national surveillance strategy for bovine viral diarrhoea (BVD) in Ireland. AB - Surveillance and management of livestock diseases is often evaluated with reference to expected sector-wide costs. In contrast, we calculate losses or savings for individual herd owners of a change in monitoring strategy during a national cattle disease eradication programme: bovine viral diarrhoea (BVD) in Ireland. The alternative strategy differs in how the disease is identified; by its sample- rather than census-based approach; and by its greater cost per test. We examined the costs faced by each breeding herd if testing were conducted using serology on a sample of young stock, in contrast to the current method of tissue tag testing of all newborn calves. Following best knowledge of the likely costs, the following input values were used: i) ?2.50 per test for tissue-tag testing and ?7.66 for serology, ii) serology conducted on a sample of 10 young stock per management group from either the 6-12 month or 9-18 month cohorts; iii) 3 scenarios for the number of management groups: one per herd (Minfinity), one per 100 cows (M100) and one per 50 cows (M50). We found that many herds would often not be able to supply a suitable sample of young stock for serology or would face higher testing costs than when using tissue tag testing. The largest number (25%) of herds would benefit from participating in the change if sampling were done in October. These could annually save between ?2.1 million under Minfinity and ?0.8 million under M50 (?108 - ?49 per herd). However, analysing herd-level data we found that 90% of all Irish breeding herds would save less than ?1.42 per cow or ?99 in total per annum under Minfinity, and ?0.59 per cow or ?36 in total under M50. In a sensitivity analysis, we allowed serology costs to vary between ?2 and ?10 per animal. Herds at the 10 t h percentile of most savings made from switching would save at most ?155 (Minfinity at ?2 per serology test) but would not save anything under M50 at costs >= ?10. We conclude that, under these assumptions, the expected reduction in testing costs for the majority of beneficiaries would barely outweigh the practical implications of the strategy switch or the risks to the eradication programme associated with sample based surveillance. This study does not assess the cost-effectiveness of alternatives post-eradication. PMID- 29786522 TI - A survey of experiences of UK cattle and sheep farmers with anthelmintic prescribers; Are best practice principles being deployed at farm level? AB - Helminths are common pathogens of ruminants. These are controlled by anthelmintics; however, resistance is a major issue. More sustainable practices need to be deployed to protect anthelmintic efficacy. There is no published information on how farmer/prescriber interactions at anthelmintic purchase shape application of best practice on-farm. To determine experiences of UK ruminant farmers as they relate to anthelmintic purchasing/provision of best practice advice at the point-of-sale, an online survey was distributed. This explored farmer experiences in purchasing anthelmintics from the three UK animal medicines' prescribers (veterinarians, Suitably Qualified Persons [SQPs], veterinary pharmacists) and investigated farmer attitudes to anthelmintic use and resistance. First, farmers were grouped according to whom they purchased anthelmintics from, including those that purchased from > 1 prescriber type. The results indicated there was no significant difference between the type of prescriber from whom farmers bought anthelmintics and route (face-to-face, telephone, online) through which they purchased them. Farmers who bought from veterinarians were more likely to view prescriber knowledge as more important. When asked who influenced purchase, there was a significant difference; farmers tended to be most influenced by the prescriber they purchased from. Those who bought from various types of prescriber were most influenced by veterinarians. Farmers who purchased from veterinarians were significantly more likely to state their seller discussed/recommended faecal egg count (FEC) testing and management strategies to reduce anthelmintic use than those who purchased from SQPs or from > 1 prescribing channel. When grouped according to purchase route, farmers that bought through face-to-face interactions were significantly more likely to state they valued prescriber knowledge of parasites/anthelmintics than farmers that purchased via the telephone or internet. Farmers that purchased online were significantly less likely to consider prescriber advice. Analysis was then applied based on the type of livestock farmed. Generally, sheep farmers undertook FEC testing more than cattle farmers. Relatively few farmers stated they conducted anthelmintic sensitivity testing, with the majority of cattle farmers having not tested at all. This was despite a high level of concern for anthelmintic resistance in all types of farmers. 'Cattle only' farmers viewed convenience factors as more important than those that managed sheep or sheep/cattle. The results suggest that UK farmers that bought anthelmintics from veterinarians were more likely to be exposed to diagnostic-led control advice. Gaps in advice provision, particularly in relation to efficacy testing, were identified in all farmer groups. PMID- 29786524 TI - Veterinary herd health management-Experience among farmers and farm managers in Swedish dairy production. AB - A preventive herd health approach will most likely reduce incidences of clinical and subclinical disease. Swedish veterinary organizations offer specific veterinary herd health management (HHM) programs, but these services are not used to a large extent. The aim of this study was to investigate dairy farmers' experience of HHM and the conditions for collaboration with veterinarians in HHM. Six focus group discussions were conducted in March 2015 in West Sweden. In total, 33 dairy farmers participated. The recordings were transcribed and coded using thematic analysis, and the transcripts were reviewed to identify potential factors indicating barriers for farmers to engage a veterinarian in HHM. The participants reported HHM to be important, but they had difficulty defining the actions included in the concept. They described a wide range of their work duties as preventive. The farmers' list of potential contributions by the veterinarians in HHM was strikingly short compared to the considerable number of preventive measures they performed themselves. Four main obstacles for farmers and farm managers to engage a veterinarian in HHM on their farm were identified in the analysis: "costs", "veterinary knowledge, skills, and organization", "farmer attitudes", and "veterinarian-farmer relationships". Costs were proposed as the main reason against engaging a veterinarian in HHM and included a high veterinary bill, low cost-benefit of veterinary services, and high costs to implement advice. Poor veterinary competence in HHM and poor knowledge about effective measures, practical farming, and farm economics were other important obstacles. Veterinarians were perceived to insufficiently describe their services and their benefits, and several participants felt they had never been offered veterinary HHM. Although veterinary HHM may be initiated by the farmer, the participants expected the veterinarian to have special responsibility for the initiation. A firm trust between farmer, staff, and veterinarian was considered crucial for veterinary HHM, but such trust takes a long time to build and can easily be disrupted by, for example, a veterinarian's poor communication skills or lack of time. Our findings suggest that Swedish dairy farmers and herd managers find disease prevention important and that they perform a wide range of tasks to prevent disease in their animals. However, they do not see what role the veterinarian can play, and veterinarians were mainly associated with treating unhealthy cows. In order to increase the use of veterinary HHM programs the services and potential benefits of such programs need to be communicated more proactively. PMID- 29786525 TI - On-farm mortality and related risk factors in Estonian dairy cows. AB - Mortality (unassisted death and euthanasia) reflects the health and welfare state of the cows and is associated with undesirable financial consequences for the farmer. The objective of this retrospective observational study was to identify risk factors associated with on-farm mortality in dairy cows. Data for a study period between January 1, 2013 and December 31, 2015 were retrieved from the Estonian Agricultural Registers and Information Board and Estonian Livestock Performance Recording, Ltd. Cows from milk-recording herds with >=20 cow-years were included. Analyses included data of 86,459 primiparous cows from 409 herds and 109,314 multiparous cows from 410 herds. Cows were followed from the day of calving until exit from the herd due to on-farm death or euthanasia (defined as mortality), slaughter, or selling. Associations between risk factors and mortality were assessed using Weibull proportional hazard models. The mortality rate (MR) was lower in primiparous cows (MR = 5.09 per 100 animal-years, 95% confidence interval [CI] 4.93; 5.26) compared to multiparous cows (MR = 8.28 per 100 animal-years, 95% CI 8.13; 8.44). The early lactation period was associated with greater mortality hazard. Animal-level factors significantly associated with higher mortality hazard in primiparous and multiparous cows were Holstein breed, older age at first calving, having an assisted calving or stillborn calf. In multiparous cows, male sex of the calf, birth of twins/triplets, older parity, longer previous inter-calving interval and milk somatic cell count over 200,000 cells/ml at the last test-milking of the previous lactation were associated with greater mortality hazard. Lower milk yield, somatic cell count over 200,000 cells/ml and fat/protein ratio over 1.5 at first test-milking were associated with greater mortality hazard during the lactation. Cow mortality risk was greater in larger herds, in herds with lower cow conception rate and poorer longevity of cows. Also, lower herd average milk fat/protein ratio and decreasing herd size (for multiparous cows) as well as Northeast region were herd level risk factors. This study outlines the importance of herd management and good health of the cows at dry-off and during early lactation and ensuring easy calving to reduce mortality of cows. PMID- 29786526 TI - Application of multiple behaviour change models to identify determinants of farmers' biosecurity attitudes and behaviours. AB - It has been recognised that few cattle farmers undertake biosecurity practices on their farms. Approaches that take into consideration individuals' preparedness for change, alongside beliefs thought to motivate the enactment of certain behaviours, may provide a framework for actuating tangible change. The aim of this study was to use a combination of behaviour change models to link beliefs with behaviour and identify possible key interventions to improve the uptake of biosecurity measures by dairy cattle farmers in Great Britain (GB). This is the first study to explore farmers' practices and attitudes in relation to the prevention of direct (animal to animal contact); indirect (via fomites); and other biosecurity measures using a multitheory approach. A cross-sectional study was carried out, with postal questionnaires sent to 2505 dairy cattle farmers. Questions were asked about the extent to which a host of biosecurity measures were used, the influence of various stakeholders (e.g. veterinarians, industry bodies) in informing biosecurity choices, and the perceived control farmers felt they had over biosecurity on their farms. Farmer attitudes towards biosecurity were also explored. Two behaviour change models, the Transtheoretical Model, and the Theory of Planned Behaviour, were utilised. A variety of analysis methods were used to interrogate the data, including multivariable logistic regression. A total of 908/2505 (36.2%) farmers responded, with 757 responses (30.2%) deemed eligible for inclusion. Farmers generally fell into one of two categories: those that reported not applying biosecurity measures with no intention of doing so in the future, and those that reported undertaking biosecurity measures for some time. Farmers felt that biosecurity improved cattle health and welfare, but also felt that disease was inevitable. More farmers agreed with statements relating to their ability to control, rather than prevent disease. Analysis suggested a difference between influencing beliefs and whether specific types of measure were more likely to be undertaken. For example, farmers' beliefs about other stakeholders appeared to play a role in influencing the utilisation of measures preventing direct contact (e.g. nose to nose contact), rather than indirect contact (e.g. fomite transmission). The use of a combination of behaviour change models has identified key variables to use for interventional approaches targeted towards the different type of biosecurity measure (preventing direct or indirect transmission) to improve the uptake of biosecurity on dairy cattle farms in GB. Other industry stakeholders should be aware of these variables when working with farmers to achieve optimal cattle herd health. PMID- 29786528 TI - Modelling correlated data: Multilevel models and generalized estimating equations and their use with data from research in developmental disabilities. AB - BACKGROUND: The use of Multilevel Models (MLM) and Generalized Estimating Equations (GEE) for analysing clustered data in the field of intellectual and developmental disability (IDD) research is still limited. METHOD: We present some important features of MLMs and GEEs: main function, assumptions, model specification and estimators, sample size and power. We provide an overview of the ways MLMs and GEEs have been used in IDD research. RESULTS: While MLMs and GEEs are both appropriate for longitudinal and/or clustered data, they differ in the assumptions they impose on the data, and the inferences made. Estimators in MLMs require appropriate model specification, while GEEs are more resilient to misspecification at the expense of model complexity. Studies on sample size seem to suggest that Level 1 coefficients are robust to small samples/clusters, with any higher-level coefficients less so. MLMs have been used more frequently than GEEs in IDD research, especially for fitting developmental trajectories. CONCLUSIONS: Clustered data from research in the IDD field can be analysed flexibly using MLMs and GEEs. These models would be more widely used if journals required the inclusion of technical specification detail, simulation studies examined power for IDD study characteristics, and researchers developed core skills during basic studies. PMID- 29786527 TI - Retrospective analysis of Bluetongue farm risk profile definition, based on biology, farm management practices and climatic data. AB - Bluetongue (BT) is a vector-borne disease transmitted by species of Culicoides midges (Diptera: Ceratopogonidae). Many studies have contributed to clarifying various aspects of its aetiology, epidemiology and vector dynamic; however, BT remains a disease of epidemiological and economic importance that affects ruminants worldwide. Since 2000, the Sardinia region has been the most affected area of the Mediterranean basin. The region is characterised by wide pastoral areas for sheep and represents the most likely candidate region for the study of Bluetongue virus (BTV) distribution and prevalence in Italy. Furthermore, specific information on the farm level and epidemiological studies needs to be provided to increase the knowledge on the disease's spread and to provide valid mitigation strategies in Sardinia. This study conducted a punctual investigation into the spatial patterns of BTV transmission to define a risk profile for all Sardinian farmsby using a logistic multilevel mixed model that take into account agro-meteorological aspects, as well as farm characteristics and management. Data about animal density (i.e. sheep, goats and cattle), vaccination, previous outbreaks, altitude, land use, rainfall, evapotranspiration, water surface, and farm management practices (i.e. use of repellents, treatment against insect vectors, storage of animals in shelter overnight, cleaning, presence of mud and manure) were collected for 12,277 farms for the years 2011-2015. The logistic multilevel mixed model showed the fundamental role of climatic factors in disease development and the protective role of good management, vaccination, outbreak in the previous year and altitude. Regional BTV risk maps were developed, based on the predictor values of logistic model results, and updated every 10 days. These maps were used to identify, 20 days in advance, the areas at highest risk. The risk farm profile, as defined by the model, would provide specific information about the role of each factor for all Sardinian institutions involved in devising BT prevention and control strategies. PMID- 29786529 TI - Corrigendum to "Adverse events associated with the use of cervical spine manipulation or mobilization and patient characteristics: A systematic review" <[Musculoskelet. Sci. Pract. 28C (2017) 32-38]>. PMID- 29786531 TI - Mechanical aspiration thrombectomy in the treatment of acute intrastent renal artery thrombosis. AB - Chimney-and-periscope technique for thoraco-abdominal aneurysm repair is a valuable treatment option in selected patients. Acute renal artery occlusion is a serious complication after this technique. We report a case of acute right renal artery occlusion, consequent to a previous chimney-and-periscope technique that was treated urgently by mechanical aspiration thrombectomy. PMID- 29786530 TI - Meta-analysis of safety and efficacy of oral anti-coagulants in patients requiring catheter ablation for atrial fibrillation. AB - BACKGROUND: The ideal oral anticoagulant agent during catheter ablation (CA) for atrial fibrillation (AF) remained unclear. HYPOTHESIS: Novel oral anticoagulants (NOACs) are safer and effective compared to uninterrupted vitamin K antagonists (U-VKA) among patients requiring CA for AF. METHODS: Four randomized controlled trials (RCTs) and 9 observational studies (OS) were selected using PubMed/Medline, EMBASE and the CENTRAL data bases (Inception-December-2017). Estimates were reported as random effects risk ratio (RR) with 95% confidence interval (CI). The primary safety outcome was major bleeding and main efficacy endpoint was thromboembolism. RESULTS: In RCTs restricted analysis, NOACs significantly reduced the relative risk of major bleeding by 72% compared to U VKA (RR, 0.28, 95% CI, 0.14-0.58, P < 0.001). This significant effect was not achieved in OS based analysis (RR, 0.86, 95% CI, 0.42-1.78, P = 0.68). In terms of thromboembolism, both anticoagulation strategies were equally effective in analysis of RCTs (RR, 0.28, 95% CI, 0.05-1.70, P = 0.17) or OS (RR, 1.43, 95% CI, 0.46-4.39, P = 0.54). In sensitivity analysis, there was no difference among uninterrupted NOACs (U-NOACs) and U-VKA in terms of major bleeding [(RCTs: RR, 0.33, 95% CI, 0.10-1.06, P = 0.06); (OS: RR, 0.70, 95% CI, 0.28-1.78, P = 0.46)] or thromboembolism [(RCTs: RR, 0.25, 95% CI, 0.03-2.29, P = 0.22); (OS: RR, 0.68, 95% CI, 0.08-5.53, P = 0.72)]. CONCLUSION: NOACs, either interrupted or un interrupted, are safer and equally effective drugs compared to U-VKA in AF patients requiring CA. PMID- 29786532 TI - Rice-body formation without rheumatic disease or tuberculosis in a "sausage" ring finger. AB - Rice bodies are very unusual lesions, generally encountered in chronic synovitis due to rheumatoid diseases or tuberculosis. A 31-year-old right-handed man presented with a 15-year history of progressively growing "sausage-like" swelling of the 4th finger and palm of his right hand. There was an immovable, painless mass with restriction of the finger's ROM without local or general associated signs. Imaging showed a large non-aggressive mass within the tendon sheath. Complete excision of the mass was performed. Histopathological examination showed synovial villi with rice bodies and central necrosis suggestive of tuberculous synovitis or rheumatoid arthritis (RA). Tests for mycobacterial infections were all negative and there was no argument in favor of a rheumatoid pathology. There is no established standard treatment in a case like ours, which has no origin in tuberculosis or RA. Prolonged follow-up will be needed to confirm absence of recurrence after complete excision. PMID- 29786533 TI - [Bacteriospermia: Effects on semen parameters]. AB - OBJECTIVES: Bacteriospermia may result in male hypofertlity. Indeed, 60% of patients treated by Assisted Reproductive Techniques had a local infection or inflammation of genital tract. However, direct effects of bacteriospermia on semen parameters remain controversial. The aim of our work was to explore the effect of bacteriospermia on sperm parameters among patients consulting for hypofertility. METHODS: A retrospective comparative study of two groups: a group of 70 patients with bacteriospermia (group 1) and a control group of 70 patients without bacteriospermia (group 2). For these groups, we studied the standard semen parameters (seminal volume and viscosity and spermatozoa count, initial and secondary mobility, vitality and morphology). Comparison of these parameters was made by the Chi2 test and the Fisher test. RESULTS: The mean age of our population was 40.4+/-6.7 years. There was no significant difference between ejaculate average volume in the 2 groups (group B: 2.78mL versus group A: 2.92mL with P=0.2). Similarly, for the viscosity no difference was noted (P=0,68). The altered parameters in the presence of bacteriospermia were mean concentration and sperm motility (P=0.001 and P=0.049 respectively). The prevalence of secondary asthenospermia was higher in the presence of bacterospermia (P=0.006). No statistically significant differences were observed for morphology and vitality of spermatozoa (P=0.276 and P=0.075 respectively). The leucospermia was associated with bacteriospermia in 10% patients. Ureaplasma urealyticum was the germ most found (45.7%) followed by Streptococcus and Staphylococcacae (20.3% for each), Gram negative rods accounted for 12.9%, while Corynebacterium spp was isolated only in 4,3% patients. U. urealyticum was associated with hypospermia in 33% of cases (P=0.031). Spermatozoa motility was significatively decreased not only in the presence of this bacteria (FT=0.002) but also when cultures were positive for Streptococcus (0.04) and Corynebacterium (P<0.001). Morphological abnormalities were also noticed with Streptococcus with index of teratozoospermia of 46% versus 19% in the 2nd group (P=0.046). CONCLUSION: Bacteriospermia may impair sperm parameters. The treatment of this affection seems to improve sperm fertilizing potential. In addition, it could prevent contamination of culture media. PMID- 29786534 TI - [The gynecological pessary: Is it really a device of another age, a fig leaf?] AB - OBJECTIVES: The use of pessary to put back up prolapsed organs to their normal position dates back prior to several millennia. This work aims to discuss its place in our clinical practice through an updated bibliographic review and emphasizes a hands-on approach to pessary fitting and management in terms of indication, pessary type selection, device' size, insertion, removal, follow-up visits and care. METHODS: A review of the literature, in the light of the latest publications and recommendations of French and international learned societies, as well as our own experience, were analyzed. RESULTS: This device appears to be as effective as surgical management to relieve symptoms related to urogenital prolapse and restore body image. It can be used temporarily, awaiting a surgical solution or as a therapeutic test (mimicking the effect of a surgical procedure to predict its functional outcome or identifying a masked urinary incontinence). It can also represent an alternative to surgery (patient choice, women who wish to complete childbearing or who are unsuitable for surgery because of medical comorbidities) and thus can be used in first intention. However, despite its moderate cost and its harmlessness, this device remains somewhat little known as regards the practical modalities of its use, which, moreover, appear not consensual. CONCLUSION: A guide intended for the attention of the patients as well as a film relating to the practical modalities of the device' use were elaborated to improve the knowledge of both professionals and users in order to optimize and secure the care pathway. PMID- 29786535 TI - Evaluating the importance of sham-controlled trials in the investigation of medical devices in interventional cardiology. AB - Cardiovascular medicine is one of the specialties that has relied most heavily on evidence from randomised clinical trials in determining best practice for the management of common disease conditions. When comparing treatment approaches, trials incorporating random allocation are the most appropriate method for protecting against treatment allocation bias. In order to protect against performance and ascertainment bias, trial designs including placebo control are preferable where feasible. In contrast to testing of medicines, treatments based on procedures or use of medical devices are more challenging to assess, as sham procedures are necessary to facilitate blinding of participants. However, in many cases, ethical concerns exist, as individual patients allocated to sham procedure are exposed only to risk without potential for benefit. Accordingly, the potential benefits to the general patient population must be carefully weighed against the risks of the exposed individuals. For this reason, trial design and study conduct are critically important to ensure that the investigation has the best chance of answering the study question at hand. In the current manuscript, we aim to review issues relating to the conduct of sham-controlled trials and discuss a number of recent examples in the field of interventional cardiology. PMID- 29786536 TI - Percutaneous coronary and structural interventions in women: a position statement from the EAPCI Women Committee. AB - Several expert documents on sex-based differences in interventional outcomes are now available, however this is the first position paper from the EAPCI Women Committee discussing the potential influence of sex in the percutaneous treatment of coronary and structural heart disease. Despite the misconception that coronary artery disease is a 'man's disease', contemporary data shows a growing incidence in women. However, women are under-represented in randomised coronary clinical trials (~25%). The generalisation of such studies is therefore problematic in decision-making for females undergoing coronary intervention. Differences in pathophysiology between sexes exist, highlighting the need for greater awareness amongst healthcare professionals to enable best evidence-based therapies for women as well as for men. Reassuringly, women represent half of the population included in transcatheter aortic valve implantation clinical trials and may actually benefit more. Growing evidence is also emerging for other interventional atrial procedures which may well be advantageous to women. Awareness of sex disparities is increasing, and we must all work collaboratively within our profession to ensure we provide effective care for all patients with heart disease. The EAPCI Women Committee aim to highlight such issues through this position paper and through visibility within the interventional community. PMID- 29786537 TI - Complete two-year follow-up with formal non-inferiority testing on primary outcomes of the AIDA trial comparing the Absorb bioresorbable scaffold with the XIENCE drug-eluting metallic stent in routine PCI. AB - AIMS: The aim of this report of the AIDA trial is to provide full two-year outcomes for the primary endpoint of target vessel failure (TVF) and an update on device thrombosis. METHODS AND RESULTS: AIDA was a single-blind, multicentre, investigator-initiated, non-inferiority, randomised (1:1) clinical trial. At complete two-year follow-up, the primary endpoint of TVF had occurred in 100 patients in the Absorb BVS arm versus 90 patients in the XIENCE EES arm (HR 1.12, 95% CI: 0.94-1.49; psuperiority=0.436). Estimated two-year Kaplan-Meier event rates of TVF were 11.0% and 9.9%, respectively (95% CI: -0.9%-3.0%; pnon inferiority=0.003). Definite or probable device thrombosis at two years occurred in 30 patients in the Absorb BVS arm and in eight patients in the XIENCE EES arm. Kaplan-Meier estimates of device thrombosis were 3.3% in the Absorb BVS arm and 0.9% in the XIENCE EES arm (HR 5.22, 95% CI: 2.00-13.59; p<0.001). CONCLUSIONS: AIDA formally met its criterion for non-inferiority of Absorb BVS versus XIENCE EES in terms of the combined endpoint of TVF. The Absorb BVS, however, was associated with higher rates of scaffold thrombosis and target vessel myocardial infarction at complete two-year follow-up. PMID- 29786538 TI - Re-shuffling the Editorial Board. PMID- 29786539 TI - Percutaneous coronary intervention in left main coronary artery disease: the 13th consensus document from the European Bifurcation Club. AB - The 2017 European Bifurcation Club (EBC) meeting was held in Porto (Portugal) and allowed a multidisciplinary international faculty to review and discuss the latest data collected in the field of coronary bifurcation interventions. In particular, the topic of percutaneous coronary intervention (PCI) on left main coronary artery (LM) disease was highlighted as a contemporary priority. Herein, we summarise the key LM anatomy features, the diagnostic modalities and available data that are relevant for a patient's procedural management. Since the clinical outcomes of patients undergoing PCI on LM disease may depend on both PCI team organisation and PCI performance, the optimal catheterisation laboratory set-up and the rationales for device and technique selection are critically reviewed. The best lesion preparation modalities, the different DES implantation technique choices and the strategies to be considered during PCI on unprotected LM for optimal PCI results are reviewed step by step. PMID- 29786540 TI - Trials of antithrombotic therapy in percutaneous coronary intervention: what evidence do we need to optimise our practice? PMID- 29786541 TI - P2Y12 inhibition in STEMI: early, strong or both? PMID- 29786542 TI - TAVR in younger patients with aortic stenosis: anything new? PMID- 29786543 TI - CTO PCI, the evolution of the revolution: time for consensus on definitions. PMID- 29786544 TI - Transcatheter aortic valve implantation in Asia: the first decade. PMID- 29786545 TI - EAPCI Presidential "criss-cross". PMID- 29786547 TI - Protective effect of breastfeeding on recurrent cough in adulthood. AB - RATIONALE: Breastfeeding protects from respiratory infections in early life but its relationship to recurrent cough and other respiratory outcomes in adult life is not well established. METHODS: Infant feeding practices were assessed prospectively in the Tucson Children's Respiratory Study, a non-selected birth cohort and categorised into formula from birth or introduced <1 month, formula introduced >=1 to <4 months and exclusive breastfeeding for >=4 months. Infant feeding was assessed as an ordinal variable representing an increasing dose of breastmilk across the three categories. Recurrent cough was defined at 22, 26 and 32 years as >=2 episodes of cough without a cold lasting 1 week during the past year. Covariates included participant sex, race/ethnicity and smoking as well as parental smoking, education, age and asthma. Covariates were evaluated as potential confounders for the relation between infant feeding and adult outcomes. RESULTS: Of the 786 participants, 19% breastfed <1 month, 50% breastfed >=1 to <4 months and 31% breastfed >=4 months. The prevalence of recurrent cough at 22, 26 and 32 years was 17%, 15% and 16%, respectively. Each ordinal increase in breastfeeding duration was associated with a decreased risk of recurrent cough in adult life: adjusted OR=0.71, (95% CI: 0.56 to 0.89), p=0.004. Additional adjustment for concurrent adult asthma, wheeze, smoking and lung volume did not change these results. CONCLUSION: Longer duration of breastfeeding reduces the risk of recurrent cough in adult life, regardless of smoking and other respiratory symptoms, suggesting long-term protective effects on respiratory health. PMID- 29786546 TI - FLT3-ITD Compared with DNMT3A R882 Mutation Is a More Powerful Independent Inferior Prognostic Factor in Adult Acute Myeloid Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study AB - Objective: This study aimed to evaluate DNMT3A exon 23 mutations and their prognostic impacts in the presence of NPM1 and FLT3 mutations in acute myeloid leukemia (AML) patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Materials and Methods: This study comprised 128 adult AML patients referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital. NPM1 and FLT3-ITD mutations were detected by fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Overall survival (OS) and relapse-free survival (RFS) curves were estimated by the Kaplan-Meier method and the log-rank test was used to calculate differences between groups. Results: The prevalence of DNMT3A exon 23 mutations was 15.6% and hotspot region R882 mutations were prominent. RFS and OS were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between these groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) in AML patients after allogeneic HSCT. In the next step, patients with AML were divided into four groups regarding FLT3-ITD and DNMT3A mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone do not affect the clinical outcomes of AML patients undergoing allogeneic HSCT, but when accompanied by FLT3-ITD mutations, the OS was significantly reduced (5-year OS 0% for DNMT3A R882mut/FLT3-ITDpos patients vs. 62% DNMT3A R882wt/FLT3-ITDneg, p=0.025) and the relapse rate increased. Conclusion: It can be deduced that DNMT3A R882mut/FLT3-ITDpos is an unfavorable prognostic factor in AML patients even after allogeneic HSCT. PMID- 29786548 TI - Designer human tissue: coming to a lab near you. AB - Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic. This special issue will guide the reader through stem cell self renewal, pluripotency and differentiation. The first articles focus on improving cell fidelity, understanding the innate immune system and the importance of materials chemistry, biofabrication and bioengineering. These are followed by articles that focus on industrial application, commercialization and label-free assessment of tissue formation. The special issue concludes with an article discussing human liver cell-based therapies past, present and future.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786550 TI - Generation of defined neural populations from pluripotent stem cells. AB - Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS). The ability to produce patient- and disease-specific iPSC lines has created a new age of disease modelling. Human iPSC may be derived from adult somatic cells and subsequently patterned into numerous distinct cell types. The ability to derive defined and regionalized neural populations from iPSC provides a powerful in vitro model of CNS disorders.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786549 TI - Pluripotent stem cells: induction and self-renewal. AB - Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells. This understanding serves two purposes: first, to enable efficient, reliable and cost-effective production of excellent quality induced PSCs and, second, to enable the derivation of safe, good manufacturing practice-grade transplantable donor cells. Here, we review the reprogramming process of somatic cells into induced PSCs and associated mechanisms with emphasis on self-renewal, epigenetic control, mitochondrial bioenergetics, sub-states of pluripotency, naive ground state, naive and primed. A meta-analysis identified genes expressed exclusively in the inner cell mass and in the naive but not in the primed pluripotent state. We propose these as additional biomarkers defining naive PSCs.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786552 TI - Intestinal organoids for modelling intestinal development and disease. AB - Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gut in vitro Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self assemble to form 'intestinal organoids'. These organoids allow for new, human specific models that can be used to gain insight into gastrointestinal disease and potentially deliver new therapies to treat them. Here we review current in vitro models of intestinal development and disease, considering where improvements could be made and potential future applications in the fields of developmental modelling, drug/toxicity testing and therapeutic uses.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786551 TI - Three-dimensional cell culture: from evolution to revolution. AB - Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissues in vitro Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responses in vitro Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids. We also highlight some of the current limitations of these systems and discuss potential avenues to further benefit biological research using three dimensional modelling technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786554 TI - A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells. AB - We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity. The high level of ZsGreen expression had no effect on the ability of macrophages to be activated to an M(LPS + IFNgamma), M(IL10) or M(IL4) phenotype nor on their plasticity, assessed by their ability to switch from one phenotype to another. Thus, targeting of the AAVS1 locus in iPSCs allows for the production of fully functional, fluorescently tagged human macrophages that can be used for in vivo tracking in disease models. The strategy also provides a platform for the introduction of factors that are predicted to modulate and/or stabilize macrophage function.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786553 TI - From skeletal development to the creation of pluripotent stem cell-derived bone forming progenitors. AB - Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors. Despite promising preclinical data, limited translation towards the clinic has been observed to date. There may be several reasons for this including the lack of robust cell populations with favourable proliferative and differentiation capacities. However, perhaps the most pertinent reason is the failure to produce an implant that can replicate the developmental programme that is observed during skeletal repair. Pluripotent stem cells (PSCs) can potentially offer a solution for bone tissue engineering by providing unlimited cell sources at various stages of differentiation. In this review, we summarize key embryonic signalling pathways in bone formation coupled with PSC differentiation strategies for the derivation of bone-forming progenitors.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786555 TI - Innate immunity in stem cell-derived hepatocytes. AB - Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs. IFN expression in HLCs is characterized by strong expression of type III IFN and low expression of type I IFN which is also a characteristic of primary hepatocytes. The response to IFN differs in HLCs with lower interferon-stimulated gene (ISG)-expression levels than in primary hepatocytes. Tumour necrosis factor-alpha (TNF-alpha) signalling is less studied in HLCs, but appears to be functional. Expression of toll-like receptors (TLR) 2 5, 7 and 9 has been reported in primary hepatocytes but has been poorly studied in HLCs. In summary, although they retain some immature features, HLCs are in many ways superior to hepatoma cell lines for cell-based modelling. In this review, we will provide an overview of innate immune signalling in HLCs and how this compares with primary hepatocytes.This article is part of the themed issue 'Designer human tissue: coming to a lab near you'. PMID- 29786556 TI - Assessment of stem cell differentiation based on genome-wide expression profiles. AB - In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue. It consists of a principal component analysis to represent global expression changes and to identify possible problems of the dataset that require special attention, such as: batch effects; clustering techniques to identify gene groups with similar features; over-representation analysis to characterize biological motifs and transcriptional control factors of the identified gene clusters; and metagenes as well as gene regulatory networks for quantitative cell type assessment and identification of influential transcription factors. Possibilities and limitations of the analysis pipeline are illustrated using the example of human embryonic stem cell and human induced pluripotent cells to generate 'hepatocyte-like cells'. The pipeline quantifies the degree of incomplete differentiation as well as remaining stemness and identifies unwanted features, such as colon- and fibroblast-associated gene clusters that are absent in real hepatocytes but typically induced by currently available differentiation protocols. Finally, transcription factors responsible for incomplete and unwanted differentiation are identified. The proposed method is widely applicable and allows an unbiased and quantitative assessment of stem cell-derived cells.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786557 TI - The gene regulatory network of mESC differentiation: a benchmark for reverse engineering methods. AB - A large body of data have accumulated that characterize the gene regulatory network of stem cells. Yet, a comprehensive and integrative understanding of this complex network is lacking. Network reverse engineering methods that use transcriptome data to derive these networks may help to uncover the topology in an unbiased way. Many methods exist that use co-expression to reconstruct networks. However, it remains unclear how these methods perform in the context of stem cell differentiation, as most systematic assessments have been made for regulatory networks of unicellular organisms. Here, we report a systematic benchmark of different reverse engineering methods against functional data. We show that network pruning is critical for reconstruction performance. We also find that performance is similar for algorithms that use different co-expression measures, i.e. mutual information or correlation. In addition, different methods yield very different network topologies, highlighting the challenge of interpreting these resulting networks as a whole.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786559 TI - Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine. AB - Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786558 TI - New substrates for stem cell control. AB - The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions. To achieve this, the chemical and physical attributes of the substrates should mimic the natural tissue environment and allow control of their biological properties. Herein, recent advances in the development of materials to study/manipulate stem cells, both in vitro and in vivo, are described with a focus on the novelty of the substrates' properties, and on application of substrates to direct stem cells.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786562 TI - Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery. AB - Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high throughput screening procedures. There are two areas within the drug discovery pipeline that the generation of a stable, metabolically functional hepatocyte like cell with unlimited supply would have major impact. First, in routine, cell health risk-assessment assays where hepatic cell lines are typically deployed. Second, at later stages of the drug discovery pipeline approaching candidate nomination where bespoke/investigational studies refining and understanding the risk to patients use patient-derived induced pluripotent stem cell (iPSC) hepatocytes retaining characteristics from the patient, e.g. HLA susceptibility alleles, iPSC hepatocytes with defined disease phenotypes or genetic characteristics that have the potential to make the hepatocyte more sensitive to a particular stress mechanism. Functionality of patient-centric hepatocyte-like cells is likely to be enhanced when coupled with emerging culture systems, such as three-dimensional spheroids or microphysiological systems. Ultimately, the aspiration to confidently use human-relevant in vitro models to predict human specific hepatic toxicity depends on the integration of promising emerging technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786561 TI - Impedance-based cellular assays for regenerative medicine. AB - Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards data-driven automation and control at the industrial scale. Impedance-based cellular assays (IBCA) have emerged as an alternative approach to study stem-cell properties and cumulative studies, reviewed here, have shown their potential to monitor stem-cell renewal, differentiation and maturation. They offer a novel method to non-destructively assess and quality-control stem-cell cultures. In addition, when combined with in vitro disease models they provide complementary insights as label-free phenotypic assays. IBCA provide quantitative and very sensitive results that can easily be automated and up-scaled in multi-well format. When facing the emerging challenge of real-time monitoring of three-dimensional cell culture dielectric spectroscopy and electrical impedance tomography represent viable alternatives to two dimensional impedance sensing.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786560 TI - Microfabrication of liver and heart tissues for drug development. AB - Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years. Technologies such as protein micropatterning, microfluidics, three-dimensional scaffolds and bioprinting have revolutionized in vitro platforms as well as increased the long term phenotypic stability of both primary cells and stem cell-derived differentiated cells. Here, we discuss advances in engineering approaches for constructing in vitro human liver and heart models with utility for drug development. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues. Overall, bioengineered liver and heart models have significantly advanced our understanding of organ function and injury, which will prove useful for mitigating the risk of drug-induced organ toxicity to human patients, reducing animal usage for preclinical drug testing, aiding in the discovery of novel therapeutics against human diseases, and ultimately for applications in regenerative medicine.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786566 TI - Clinical Performance Measures for Adults Hospitalized With Intracerebral Hemorrhage: Performance Measures for Healthcare Professionals From the American Heart Association/American Stroke Association. PMID- 29786564 TI - Developing defined substrates for stem cell culture and differentiation. AB - Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell-matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786567 TI - How to incorporate academic writing pedagogy in undergraduate and postgraduate medical education. AB - OBJECTIVE: Introduction: Medical researchers, who are non-native English speakers, are facing now the growing need to publish their research results in international journals switching to an English-only policy, to apply for grants and scholarship, but at the same time this puts many authors whose native language is not English at a disadvantage compared to their English-speaking counterparts. The aim: This paper aims at analysing the existing parameters of academic writing proficiency of medical undergraduate and postgraduate students; elucidating current approaches to develop academic writing competency and to promote academic multi-literacy of junior researchers, and outlining the general recommendations to improve the quality and sophistication of their writing by incorporating the principles and achievements of academic writing pedagogy into the system of medical training. PATIENTS AND METHODS: Materials and methods: This study is an empirical applied research of a qualitative type mainly based on data elicited from informants (n=120) of the Ukrainian Medical Stomatological Academy aged from 20 - 35. RESULTS: Results and conclusions: All participants were able to identify personal problem areas, and virtually all they note dissatisfaction with the use of English in their scholarly writing. They stated the obvious difficulties in sentence patterns and keeping tone of scientific narrative format. Writing in genres other than original research articles seems to be quite demanding and is often associated with the lack of self-confidence and language anxiety. Attention to developing academic writing skills should focus on the basic elements of academic writing, characteristics of written genres across the disciplines, providing a framework in which expert and practical knowledge is internally organized. PMID- 29786565 TI - Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation (TET) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis. Hepatocyte-like cells (HLCs) derived from human embryonic stem cells can provide a non-neoplastic, renewable model for liver research. Here, we have developed a model of NAFLD using HLCs exposed to lactate, pyruvate and octanoic acid (LPO) that bear all the hallmarks, including 5hmC profiles, of liver functionality. We exposed HLCs to LPO for 48 h to induce lipid accumulation. We characterized the transcriptome using RNA-seq, the metabolome using ultra-performance liquid chromatography-mass spectrometry and the epigenome using 5-hydroxymethylation DNA immunoprecipitation (hmeDIP) sequencing. LPO exposure induced an NAFLD phenotype in HLCs with transcriptional and metabolomic dysregulation consistent with those present in human NAFLD. HLCs maintain expression of the TET enzymes and have a liver-like epigenome. LPO exposure-induced 5hmC enrichment at lipid synthesis and transport genes. HLCs treated with LPO recapitulate the transcriptional and metabolic dysregulation seen in NAFLD and additionally retain TET expression and 5hmC. This in vitro model of NAFLD will be useful for future mechanistic and therapeutic studies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786563 TI - Cell-based liver therapies: past, present and future. AB - Liver transplantation represents the standard treatment for people with an end stage liver disease and some liver-based metabolic disorders; however, shortage of liver donor tissues limits its availability. Furthermore, whole liver replacement eliminates the possibility of using native liver as a possible target for future gene therapy in case of liver-based metabolic defects. Cell therapy has emerged as a potential alternative, as cells can provide the hepatic functions and engraft in the liver parenchyma. Various options have been proposed, including human or other species hepatocytes, hepatocyte-like cells derived from stem cells or more futuristic alternatives, such as combination therapies with different cell types, organoids and cell-biomaterial combinations. In this review, we aim to give an overview of the cell therapies developed so far, highlighting preclinical and/or clinical achievements as well as the limitations that need to be overcome to make them fully effective and safe for clinical applications.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. PMID- 29786568 TI - Nutritive support for newborns in critical conditions: semi-elemental formilas as a means of enteral nutrition. AB - OBJECTIVE: Introduction: The goal is to increase the efficiency of nutritional support in intensive care of newborns by substantiating the choice of the enteral blend. PATIENTS AND METHODS: Materials and methods: A prospective cohort study was conducted, which included 173 newborns. The main group consisted of 143 patients of intensive care units. The comparison group - 30 virtually healthy newborns. Physical parameters, changes in protein metabolism, serum immunoglobulins, functioning of the gastrointestinal tract and hepatobiliary system in the development of critical conditions and depending on the type of enteric urine formula were determined. RESULTS: Results: At the beginning of newborn enteral nutrition in the main group, (46.15% of cases), there were signs of gastrointestinal malformation, distributions were detected in protein metabolism, decreased serum immunoglobulin fractions, gastroduodenal cytoprotection, increased alkaline phosphatase activity. Against the background of the use of semi-elemental hydrolysable formulas a greater frequency of excretions was observed, the assimilation orientation of protein metabolism, increased levels of serum immunoglobulin fractions, reduction of gastroduodenal cytoprotection, reduction of laboratory characteristics cholestasis and damage to hepatocytes. CONCLUSION: Conclusions: In newborns in critical conditions, adaptation to the onset of enteral nutrition is accompanied by a catabolic direction of metabolism. The use of semi-elemental formulas increases the efficiency nutritional support in the intensive care of newborns. PMID- 29786569 TI - [An assessment of the functional status in the neurorehabilitation of patients after ischemic stroke]. AB - OBJECTIVE: Introduction: In this article, the authors focused on the symptoms of ischemic stroke and the effect of neurorehabilitation methods on the functional status of patients after ischemic stroke. The aim of the study was to evaluate and compare the functional status of patients after ischemic stroke with improved classic kinesiotherapy, classic kinesiotherapy and NDT-Bobath and classic kinesiotherapy and PNF. PATIENTS AND METHODS: Materials and methods: The study involved 120 patients after ischemic stroke. Patients were treated in the Department of Rehabilitation and Physical Medicine USK of Medical University in Lodz. Patients were divided into 3 groups of 40 people. Group 1 was rehabilitated by classical kinesiotherapy. Group 2 was rehabilitated by classic kinesiotherapy and NTD-Bobath. Group 3 was rehabilitated by classical kinesiotherapy and PNF. In all patient groups, magnetostimulation was performed using the Viofor JPS System. The study was conducted twice: before treatment and immediately after 5 weeks after the therapy. The effects of applied neurorehabilitation methods were assessed on the basis of the Rivermead Motor Assessment (RMA). RESULTS: Results: In all three patient groups, functional improvement was achieved. However, a significantly higher improvement was observed in patients in the second group, enhanced with classical kinesitherapy and NDT-Bobath. CONCLUSION: Conclusions: The use of classical kinesiotherapy combined with the NDT-Bobath method is noticeably more effective in improving functional status than the use only classical kinesiotherapy or combination of classical kinesiotherapy and PNF patients after ischemic stroke. PMID- 29786571 TI - [The disorders of the musculoskeletal system in patients hospitalized in the geriatric ward]. AB - OBJECTIVE: Introduction: In recent years the interest in the quality of life in old age has been rising, which no doubt is closely linked with the growing population of elderly people. The problems associated with declined functionality of the locomotor system, which naturally occur with age, contribute to increasing morbidity in elderly patients. It is known that lack of exercise can lead to increased aging and disability. Applying the Senior Fitness Test (SFT) allows to explore and assess the patient's mobility. The aim: To evaluate the functioning of the patients hospitalized in the geriatric ward and realize them using the method of the Senior Fitness Test (SFT). PATIENTS AND METHODS: Materials and methods: The study involved 60 elderly subjects, including 30 men and 30 women in four age groups: 75-79, 80-84, 85-89, 90-94. The research was carried out in the Department of Internal Medicine and Geriatrics at the University Hospital in Krakow. Within the group, the functional mobility of patients was assessed by Senior Fitness Test (SFT), that means that the upper-body and the lower-body strength, the upper-body and the lower-body flexibility, cardiovascular endurance and finally the patient's agility and balance were measured by individual tests. RESULTS: Results: In the study group in the assessment of functional capacity, patients usually have difficulties in getting up from a chair, lifting heavy objects, more bending, dressing, lifting hands, moving. The obtained results of all studies assessed activities are significantly deviateng from the correct results. None of the patients did not perform all tests in accordance with the standards laid down for the ages. CONCLUSION: Conclusions: We conclude that in the study population of hospitalized elderly functional ability presents a very unfavorable. PMID- 29786570 TI - Combination of metformin and pioglitazone and its effect in treatment of comorbid pathology. AB - OBJECTIVE: Introduction: The early development and high incidence of cardiovascular lesion in patients with type 2 diabetes mellitus is one of the most serious challenges for the diabetology worldwide. The aim: The purpose of the paper is to determine the dynamics of the insulin resistance indices in patients with type 2 diabetes mellitus concomitant with coronary heart disease in the combination therapy with metformin and pioglitazone during 3 and 6 months. PATIENTS AND METHODS: Materials and methods: 95 patients with type 2 diabetes mellitus and coronary heart disease have been treated and randomized into two groups: the comparison group (n=37), treated with metformin and sulfonylureas, and the study group (n=58), treated with metformin in combination with pioglitazone. Prior, after 3 and 6 months of treatment C-peptide was assessed and index of the insulin resistance was calculated. RESULTS: Results: The resulting data proved the statistically significant lowering of the markers and level of the insulin resistance under the effect of combination treatment with metformin and pioglitazone. CONCLUSION: Conclusions: The proposed variant of the combination therapy has a positive effect on the clinical course of the coronary heart disease in patients with type 2 diabetes mellitus, well tolerated by the patients and can be considered as the pathogenetic factor in the treatment of these diseases. PMID- 29786572 TI - Dysadipokinemia in patients with gout and its association with the disease activity. AB - OBJECTIVE: Introduction: In recent years, the role of adipokines in the development of rheumatic diseases has been a pressing issue. The available data suggest the dysadipokinemia in patients with rheumatoid arthritis, osteoarthritis and psoriatic arthritis. However, there is no data on changes in the levels of adipokines in patients with gout and their association with the activity of inflammatory process. The aim was to study the levels of adipokines in gout patients and evaluate their association with the disease activity. PATIENTS AND METHODS: Materials and methods: We examined 151 male patients with gout. The control group consisted of 31 practically healthy men, represented by age. We used the Gout Activity Score (GAS) to assess gout severity. The levels of leptin and adiponectin were determined using the ELISA kit. For comprehensive evaluation of dysadipokinemia, we used a logarithmic ratio of leptin to adiponectin (lg A/L). Primary processing of results was carried out using MS Excel and Statistica SPSS22 statistical software packages. RESULTS: Results: The patients with gout demonstrated higher leptin levels, lower levels of adiponectin, and lower lg A/L compared to practically healthy individuals. Among patients with gout, the disturbance of adipokin status was most pronounced in patients with tophi. Patients with high GAS activity had maximum disturbance of adipokin profile by lg A/L, while the manifestations of dysadipokinemia were minimal in the group with low activity of the disease. It was established that GAS disease activity, BMI, and the number of joints under attack may be considered the most significant independent predictors of dysadipokinemia. CONCLUSION: Conclusions: The patients with gout presented an increase in leptin level, a decrease in adiponectin level, and a decrease in the ratio lg A/L. Dysadipokinemia was associated with high disease activity and could serve as a prognostic factor for assessing the severity of the disease. PMID- 29786573 TI - Analysis of electromyographic indexes of temporal and masticatory muscles in patients with distal occlusion complicated by dental crowding. AB - OBJECTIVE: Introduction: Rate of distal occlusion (up to 40%) and dental crowding (up to 65%) is the largest in the structure of orthodontic pathology. The aim of the study was to investigate bioelectrical activity of temporal and masticatory muscles and to set parameters of electromyographic indexes in patients with distal occlusion and dental crowding in permanent occlusion. PATIENTS AND METHODS: Materials and methods: Bioelectrical activity of temporal and masticatory muscles in 11 patients aged 16-24 years was determined before orthodontic treatment. Distal occlusion complicated by severe degree of dental crowding was revealed in this group of patients. These patients comprised the treatment group. The control group consisted of 10 subjects (mean age 21,3 +/- 1,25 years) with physiological occlusion. RESULTS: Results: It was found that functional state of temporal and masticatory muscles in patients with distal occlusion complicated by dental crowding changes during permanent dentition. It was determined that in clenching state, according to ACTIV index, temporal muscles are more active, due to the lack of activity of masticatory muscles (ACTIV =-20,73% +/- 8,01%). Moreover it is worthy of notice, that functional muscle symmetry (index SIM TA/MM) at rest in presence of distal occlusion is lower than in subjects with physiological occlusion (p <0,05). CONCLUSION: Conclusions: According to index ACTIV TA/MM it was established the dominance of temporal muscle activity due to lack of activity of masticatory muscles in patients with distal occlusion complicated by dental crowding and it was determined lower overall muscle symmetry index than in individuals with physiological occlusion. PMID- 29786574 TI - THE INCREASE OF EFFICIENCY OF TREATMENT IN PATIENTS WITH NON-STABLE ANGINA PECTORIS WITH USE OF NITROGEN OXIDE DONATOR AB - OBJECTIVE: Introction: One of the leading pathogenetic factors of CVD is a violation of the function of the endothelium of the vessels, which leads to endothelial dysfunction. The aim: Increasing the efficiency of treatment of patients with NSAP based on the study of the dynamics of clinical picture, blood parametres, CRP, indices of endothelium dependent vasodilatation of the brachial artery with the use of arginine hydrochloride. PATIENTS AND METHODS: Materials and methods: The 45 patients with non-stable angina pectoris (NSAP), who were in inpatient treatment in the cardiological department of the Clinical city hospital of emergency care in Lviv, were examined. The average age of patients was 56.8 +/ 4.9 years. The patients were divided into 2 groups depending on the treatment. The first group (22 patients) took the common basic therapy, based on the standards of treatment of patients with NSAP. Another group (23 patients) received common standard (basic) treatment plus arginine hydrochloride, as a endothelial protector. The control group included 15 practically healthy individuals. The statistical analysis of the materials was carried out using the Statistica 8.0 program with the definition of the Student's t-criterion. RESULTS: Results: When complex treatment of patients with NSAP using arginine hydrochloride improves the clinical picture faster than with basic therapy. After treatment, statistically significant changes in the lipid profile of the blood were observed only in the group of patients who underwent complex therapy with arginine hydrochloride, the level of total cholesterol, LDL cholesterol and atherogenic index decreased, HDL cholesterol increased compared with those before treatment. After the complex treatment, the rate CRP decreased on 40,8% (p <0,05) and on 29,7% (p> 0,05) in the basic therapy. After 30 days of treatment in the group of patients with intermittent use of arginine aspartate, a positive trend was observed in 74% of patients, considering that endothelial dysfunction was detected in 95.1% of patients before treatment. CONCLUSION: Conclusions: Comprehensive treatment of patients with NSAP using arginine hydrochloride is more effective than basic therapy, as evidenced by faster normalization of the clinical picture of the disease, laboratory blood parameters, and improvement of the function of the endothelium. PMID- 29786575 TI - Spatial organization of the excretory ducts and sections of microcirculatory blood flow of the labial salivary glands in older adults. AB - OBJECTIVE: Introduction: Salivary glands have a significant impact on the state of the homeostasis of the human body, oral cavity in particular, sensitively responding to pathological processes. The reactivity of the salivary glands in response to pathological processes that are organically linked to morphology and functions of the organ's structures, and particularly the excretory ducts of the glands and their microcirculatory blood flow, is one of the problems which have not been solved to date. The aim of the paper was to elucidate the features of the stereomicroscopic structure of the excretory ducts and sectors of the microcirculatory blood flow in labial glands of older adults. PATIENTS AND METHODS: Materials and methods: The object of the study was the labial mucosa of the older adults, which was cut into 3x3 mm pieces and fixed in the buffered 4% glutaraldehyde solution with subsequent 2-hour fixation in osmium. Once the pieces were washed and dehydrated they were embedded into the Epon-812. The series of the semi-thin sections, made from the obtained epoxy blocks, were stained in phosphate buffered 0,1% toluidine blue solution. The serial semi-thin sections were subjected to histological and cytological studies and multilayered plastic reconstruction. RESULTS: Results and conclusions: The series of histological epoxy semi-thin sections, as well as graphic and plastic reconstruction of the sectors of microcirculatory blood flow and excretory ducts of the human labial glands have demonstrated a range of morphological facts that can be used to clarify the intertissue stereological relationships. They also determined the syntopic proximity of the capacitive sectors of microcirculatory blood flow to the excretory ducts of the gland. Such pattern is especially notable in the collecting venules and intralobular ducts. It has been shown that the biggest venule is the collecting venous vessel. Anastomoses between the intralobular arterioles and collecting venules have been found in the microcirculatory blood flow of the labial glands. PMID- 29786576 TI - The histological and electron microscopic study of the parotid salivary gland in dehydrated rats of different ages. AB - OBJECTIVE: Introduction: Water-salt metabolism disorders is one of the main factor of salivary gland pathology development. The aim: To study the morphological structure of the parotid salivary gland of young, mature and old rats at micro- and ultrastructural levels under water deprivation. PATIENTS AND METHODS: Materials and methods: The experiment was carried out on thirty six laboratory male rats of different ages (young, mature and old). The rats of the control group received normal volume of drinking water. The rats of the experimental group were deprived of water for 6 days. Light microscope "OLYMPUS" and transmission electron microscope JEM-1230, (JEOL, Japan) were used for structural analysis. RESULTS: Results: Obtained results revealed increasing numbers of vacuoles in the serous cells, the enlarged cisterns of endoplasmic reticulum and Golgi apparatus tubules, the condensed chromatin and the nuclei with significant invaginations in parotid gland of the rats of all age groups. The area of the acinuses more changed in young rats, the decrease was 34.61 % (P = 0.007). The internal diameter of capillaries most decreased in the dehydrated old rats by 23.76 % (P = 0.009) in comparison with all study groups. CONCLUSION: Conclusions: Water deprivation brings about the structure changes of the parotid gland at micro- and ultrastructural levels the intensity of which depends on the age of animals. The most dramatic changes have occurred in young and old rats. PMID- 29786577 TI - Post-stroke fatigue and its dimensions over the second half year after stroke. AB - OBJECTIVE: Introduction: Post-stroke fatigue (PSF) is a common and often debilitating sequel of both ischemic and hemorrhagic strokes. The aim: Assess the rates and intensities of PSF over the second half year after stroke. PATIENTS AND METHODS: Materials and methods: There were examined 128 patients at 6, 9 and 12 months after ischemic or hemorrhagic stroke onset. PSF was measured by fatigue assessment scale (FAS), multidimensional fatigue inventory-20 (MFI-20) and fatigue severity scale (FSS). Distributions of continuous variables were checked by Shapiro-Wilk test. Parametric variables were represented as mean+/-standard deviation, non-parametric - as mediana (Me) and interquartile (25%-75%) range (Q1 Q3). Categorical data were represented by number (n) and percentage. The difference between the patients' proportions with PSF at definite time points after stroke onset was assessed using Cochran's Q-test. The Friedman F-test for repeated measurements was performed to analyze multiple non-parametric variables. When the Friedman F-test yielded a significant effect (p<0,05), it was followed by Dunnett's test for determination the differences between initial and subsequent measurements. A p-value <0,05 was considered statistically significant. RESULTS : Results: According to FAS and MFI-20 "global fatigue" sub scale, PSF rates over the second half year after stroke were statistically stable and were present, respectively, in 28,1% and 34,0% at 6 months, in 26,2% and 32,4% at 9 months, in and 32,0% and 30,5% cases at 12 months after stroke. Physical, mental, activity-related and motivational PSF domains, due to MFI-20 sub-scales, had roughly similar percentage without any significant dynamics over the studied period. According to FSS value ranks, proportions of patients with different levels of PSF impact on daily life were statistically stable over the studied post-stroke period. However, it has been revealed significant reduction of PSF intensities in physical and activity-related domains whereas severities of mental and motivational PSF aspects have been statistically increased. CONCLUSION: Conclusions: Rates of PSF were stable over the second half year after stroke occurrence, however intensities of mental and motivational PSF domains have been statistically increased, whereas severities of physical and activity related PSF domains have been significantly decreased. PMID- 29786578 TI - [Influence of basic dental materials on indicators of free radical oxidation and antioxidant blood's potential of white rats (experimental study)]. AB - OBJECTIVE: Introduction: Basic materials used in the clinic of orthopedic dentistry are high-polymer compounds and have a number of positive properties in certain conditions. The main group of materials for manufacturing of removable dentures is acrylic plastics of hot polymerization. However, such materials can sometimes cause a number of complications. Using removable prostheses, which are made of acrylic plastics can cause the development of an allergic or toxic chemical reaction of tissues of the prosthetic bed. The question of improving the quality of removable prosthesis is one of the most important problems for many years because of reactions of people's organism they can cause. This aim is achieved by development of new basic dental materials and improvements at various stages of the process of manufacturing removable plate prostheses. The aim: To investigate the possible adverse effect of various groups of basic dental materials on some hematological parameters of white male rats in the Wistar line. PATIENTS AND METHODS: Materials and methods: Experiments were performed on 20 white male Wistar rats weighing 160-200 grams. The choice of this species was based on the literature data on the use of white rats in the study of the biological effects of plastics, solvents, dyes, and others. Freshly made samples of the studied materials were used in experiments, because the maximum allocation of monomer occurs in the first 7 days after polymerization. Euthanasia of animals was performed 7 days after surgical intervention under hexenal anesthesia by blood transfusion from the right ventricle. The object of the study was the venous blood of experimental animals. RESULTS: Results: On the seventh day after substrate samples of basic materials Ftorax, Deflex Acrylato and Vertex ThermoSens intramuscularly into the anterior abdominal wall, white laboratory rats did not have results, such as some unnormal reaction of the animal's organism. A slight increase in the value of the index of spontaneous hemolysis of erythrocytes (5.8+/-0.5%) in the group of animals, which was sampled with the material "Ftorax" in comparison with the control group (4.6+/-0.3%), has no statistically significant difference. Similarly, there is no significant increase in the accumulation of TBC-reactants in this group to a value of 4.48+/-0.28 MUmol/l compared with the group of pseudo-operated animals (3.02+/-0.41 MUmol/l), which is not statistically significant. Thus, it can be stated that according to the parameters of free radical oxidation, the biological reaction of the animal organism to the incorporation of the aforementioned materials was not revealed. CONCLUSION: Conclusions: The results of the study of the biological effect of basic dental plastics on white rats by stacking samples of investigated material into the anterior abdominal wall evaluated by free radical oxidation and activity of antioxidant enzymes did not reveal statistically significant differences comparing with the control group of animals. PMID- 29786579 TI - Operative treatment of corrosive esophageal strictures. AB - OBJECTIVE: Introduction: Nowadays operative treatment of corrosive esophageal strictures remains one of the difficult and unsolved problems in surgery. The level of postoperative complications such as anastomotic leak (develops in 7-30% of cases), infections, pneumonia, pleural empyema, mediastinitis, peritonitis, postoperative corrosive strictures is still rather high. The aim of our work was to improve the results of surgical treatment of patients with corrosive esophageal strictures by analyzing and refining on conservative therapy options as well as differentiated approach to each operative treatment method. PATIENTS AND METHODS: Materials and methods: 44 patients with corrosive esophageal strictures operatively treated during the period of 1993-2017 were examined. Indications for each of esophagoplasty techniques were established. In colon bypass of the esophagus (26 patients) infusion therapy for prevention of ischemic transplant disorders, roentgenologic and prevascular preparation of future colonic transplant, anti-reflux colonogastric anastomosis were suggested. In gastric esophagoplasty (10 patients), clinically modified transhiatal extirpation of the esophagus with gastric tube plastics, an original method of lengthening of gastric graft, is preferred in clinical practice. Two patients underwent ileocecal segment esophagoplasty because of simultaneous esophageal and gastric lesion or colon diseases. RESULTS: Results: The best method of esophagoplasty associated with a small number of postoperative complications is clinically modified gastric tube esophagoplasty with formation of single extrapleural esophagogastric anastomosis. In cases when the stomach cannot be used and the marginal artery is well marked, isoperistaltic retrosternal colonoplasty with preservation of blood supply due to the left colonic artery is indicated. Suggested method of ileocecal segment esophagoplasty is used in simultaneous esophageal and gastric lesion, providing the formation of relevant reservoir (the cecum instead of the stomach), antireflux mechanism and preventing the development of peptic ulcers and transplant strictures. CONCLUSION: Conclusions: Operative treatment of corrosive esophageal strictures remains a great challenge for surgeons and should be based on individual choice of proper method of esophagoplasty and final intraoperative decision making. PMID- 29786580 TI - [Iron deficiency reduces systemic inflammation in obese women]. AB - OBJECTIVE: Introduction: Iron plays an important role in the functioning of immunological monitoring due to its stimulating and differentiating effect on the immune system. Obesity is accompanied by chronic low grade inflammation and may be accompanied by a change in the concentration of iron in the blood serum. The aim of the study was to determine the level of systemic inflammation in iron deficiency anemia in patients with obesity. PATIENTS AND METHODS: Materials and methods: 40 women with iron deficiency anemia (30 with obesity and 10 without obesity) and 10 with obesity of a similar age (control group) participated in the study. We evaluated hemogram parameters, indicators of iron exchange (serum iron, ferritin, hepcidin, total iron binding capacity, transferrin saturation) and inflammatory markers: C-reactive protein and interleukin-6 in the blood serum. RESULTS: Results: All patients were females with an average age of 40.3 +/- 7.59 years. In the distribution of patients by the cause and the severity degree of iron deficiency anemia, there is no probable difference between the groups. C reactive protein was significantly higher in women in the control group as compared with the groups of women with iron deficiency anemia (p <0.05). Meanwhile, the groups with iron deficiency anemia had insignificant differences (p> 0.05). Interleukin-6 also had a higher level in the control group as compared with the groups of women who had iron deficiency anemia (p <0.05) and, in contrast to the C-reactive protein of the group with iron deficiency anemia, had a significant divergence (p <0.05). Hepcidin of blood serum was higher in women with iron deficiency anemia without obesity (p<0.05) as compared to women with obesity and control group who did not have a significant difference (p> 0.05). CONCLUSION: Conclusions: The level of systemic inflammation in iron deficiency anemia in patients with obesity is lower than in patients with iron deficiency anemia, which was determined by levels of interleukin-6 and C-reactive protein in the blood serum. PMID- 29786581 TI - Development of informational-communicative system, created to improve medical help for family medicine doctors. AB - OBJECTIVE: Introduction: Today mobile health's protection service has no concrete meaning. As an research object it was called mHealth and named by Global observatory of electronic health's protection as "Doctor and social health practice that can be supported by any mobile units (mobile phones or smartphones), units for patient's health control, personal computers and other units of non-wired communication". An active usage of SMS in programs for patients' cure regimen keeping was quiet predictable. Mobile and electronic units only begin their development in medical sphere. Thus, to solve all health's protection system reformation problems a special memorandum about cooperation in creating E-Health system in Ukraine was signed. The aim: Development of ICS for monitoring and non-infection ill patients' informing system optimization as a first level of medical help. PATIENTS AND METHODS: Materials and methods: During research, we used systematical approach, meta-analysis, informational-analytical systems' schemes projection, expositive modeling. Developing the backend (server part of the site), we used next technologies: 1) the Apache web server; 2) programming language PHP; 3) Yii 2 PHP Framework. In the frontend developing were used the following technologies (client part of the site): 1) Bootstrap 3; 2) Vue JS Framework. RESULTS: Results and conclusions: Created duo-channel system "doctor-patient" and "patient-doctor" will allow usual doctors of family medicine (DFM) take the interactive dispensary cure and avoid uncontrolled illness progress. Doctor will monitor basic physical data of patient's health and curing process. The main goal is to create automatic system to allow doctor regularly write periodical or non-periodical notifications, get patients' questioning answers and spread information between doctor and patient; that will optimize work of DFMs. PMID- 29786582 TI - Characteristics of epidemiology of dental caries in children from regions with high and optimum fluorine content in drinking water. AB - OBJECTIVE: Introduction: Prevention of dental diseases in children is the priority item on the modern dentistry agenda. Among the undeniable factors known as contributing into caries incidence, there is fluoride content in the external environment, especially in drinking water, which is the main source of fluoride intake. The aim: This study is aimed at evaluating dental caries indices in children and adolescents inhabiting in areas with optimal and high-level fluoride concentration in drinking water and assessing their level of oral hygiene. PATIENTS AND METHODS: Materials and methods: To explore the caries epidemiology in the regions with optimal and high fluoride content, we examined 315 children aged 6, 12 and 15 who live in the city of Poltava (fluoride content in drinking water is 0.9-1.2 mg / l) and 91 children of the same age residing in the village of a town type Mashivka (fluoride content in drinking water ranges from 1.7 to 2.9 mg / l). RESULTS: Results: More than half of the 6-year-old children of both groups have decayed teeth. The comparative analysis of the prevalence and intensity of caries in the children aged 12 and 15 years demonstrated a significant increase in the number of individuals diagnosed to have caries with increasing age in both groups. CONCLUSION: Conclusions: Our research suggests that, along with the number of other cariogenic factors, fluorosis contributes to a more intense course of caries progression. This situation demands wider health policy measures to support primary and secondary caries prevention and management among the children. PMID- 29786583 TI - Incidence and risk factors of spina bifida in children. AB - OBJECTIVE: Introduction: The pathogenesis of spina bifida depends on time, region, race and ethnicity. It is found in 4.7 per 10.000 of live born children worldwide. The aim: The incidence in children of Northern Bukovina was analyzed. The spina bifida incidence for 2007-2016 in this region, as well as, compared to some countries according to EUROCAT data was studied. PATIENTS AND METHODS: Materials and methods: A retrospective study to analyze the risk factors for spina bifida was carried out. A case-control study was conducted using clinical records of 34 children with this pathology (16 boys and 18 girls) aged 0-18 years living in Northern Bukovina. 44 case records of healthy children (26 boys and 18 girls) were compared. RESULTS: Results: According to EUROCAT, the prevalence of spina bifida in the studied countries varied in the range of 0.13-0.500/00. The spina bifida incidence in Northern Bukovina (0.22 0/00) does not exceed the statistics for Ukraine (0.29 0/00) throughout the study period. CONCLUSION: Conclusions: This study provides a comprehension overview of a number of factors determining spina bifida risks: third pregnancy, miscarriage, high emotional stress during pregnancy, TORCH infection in pregnant, poor housing, maternal age, co-habiting, residence near contaminated lands, hard physical work preconceptionally, smoking habits, military service, etc. The most probable spina bifida preventive factors in children are: high school education of parents and using folic acid during the first trimester of pregnancy. Nevertheless, our data present new factual material, which requires further in-depth study, it is already clear that all the above indicators are associated with increased risk for spina bifida-complicated pregnancies. PMID- 29786584 TI - Effect of atmospheric technogenic emissions on health indicators of child population. AB - OBJECTIVE: Introduction:The identification of scientifically grounded dependency of the atmospheric pollution effect on the health level of the child population within particular area makes it possible to assess the degree of district environmental safety and provides the possibility for implementation of targeted programs and risk preventing strategies associated with atmospheric emissions. The aim of the study is to assess the dependence of child morbidity rate development caused by atmospheric chemical pollution, which resulted from the stationary and mobile sources activity in terms of the Poltava region (Ukraine) as a model. PATIENTS AND METHODS: Materials and methods: Analysis of the general morbidity rate, respiratory diseases and congenital malformations rate was based on statistical data of the Poltava Regional Health Department, the assessment of air pollutant emissions level in cities and districts of the region over 2011 2015 years was performed using data provided by the Main Statistics Department of the Poltava region and the Department of Ecology and Natural Resources of the Poltava Region State Administration; the Microsoft Excel package with Pearson correlation coefficient and two-choice Student's t-test was used for the data analysis. RESULTS: Results: According to the research data it was determined that each district had its own specific features in environmental hazards formation and common correlation pattern for all 25 administrative districts of the Poltava region was not specified. Ranking of regions by the level of pollutant emission effect on the child morbidity rate makes it possible to distinguish more dangerous ecological regions. Eight areas with significant and moderate relations between the child morbidity rate and air pollution caused by mobile sources and seven areas where air pollution was caused by stationary ones have been revealed. The main sources of air pollution are industrial emissions of the fuel and energy enterprises, manufacturing and extractive industries, vehicle and agriculture emissions. Kremenchuk and Horishni Plavhi cities include more significant factors in formation of child morbidity rate. CONCLUSION: Conclusions: Considering identified factors and dependencies, the targeted regional program aimed at specification, elimination and prevention of the harmful environmental factor affecting children's health can be projected. PMID- 29786585 TI - Hygienic assessment of the effects of pesticides application on adult population morbidity with thyroid gland diseases. AB - OBJECTIVE: Introduction: It is proved that some groups of fungicides and herbicides are capable of affecting the thyroid gland, provoking its growth, leading to a compensatory change in the activity of the hormones synthesis. Therefore, the presence of their residual amounts in plant may affect the level of thyroid gland pathology. The aim of the work was to analyze the influence of pesticide application on the Ukrainian adult population morbidity with thyroid diseases in the period from 2001 to 2014. PATIENTS AND METHODS: Materials and methods: The methods of empirical and theoretical research of scientific information, namely analysis, synthesis, induction, deduction and systematization, epidemiological, cartographic and statistical methods were used. RESULTS: Results: The maximum level of thyroid pathology was found in the northern, western and northwestern regions, where the diffuse goiter dominates in the morbidity and prevalence of thyroid diseases; minimal - in the southern, eastern and south-eastern regions. It was established that the highest volumes of application of chemical plant protection products in the period 2001-2013 took place in the southern and central regions of Ukraine, namely in Poltava, Vinnitsa, Kharkiv, Dnipropetrovsk, Khmelnytsky, Odesa and Mykolaiv regions. Sufficiently high levels of pesticide application were in the Kyiv, Kherson regions, Crimea, Zaporizhia, Kirovograd and Cherkasy regions. CONCLUSION: Conclusions: The probability of the active chemical plant protection products usage effect on the level of prevalence and incidence of thyroid cancer, various types of goiter, hypothyroidism, thyrotoxicosis and thyroiditis in the central and southern regions was determined. Are regions with well-developed agricultural production. PMID- 29786586 TI - [Eating habits of the youth from Ruda Slaska]. AB - OBJECTIVE: Introduction: In recent years, interests on dietary and health food have grown considerably. Nutritional knowledge and eating habits determined in the youth have an impact on the health condition in adulthood. The aim: To evaluate the eating habits in the population of young people from Silesian province. PATIENTS AND METHODS: Materials and methods: The anonymous questionnaire survey was conducted in the group of high school students aged 17 21 years coming from Silesian province, randomly chosen from high schools in Ruda Slaska. The study group consisted of 262 students, 157 (59,9%) women and 105 (40,1%) men. The student's participation in the study was voluntary. RESULTS: Results: The analysis showed that as many as 40% of high school students never eat regularly and eating of regular meals reported only 11,5%. Less than a half (46,9%) of participants eat breakfast every day. The most commonly consumed meals was lunch (n = 217; 82,8%) and dinner (n = 143; 54,6%). The vast majority of students (77,5%) didn't know the correct classification of the feeding pyramid floors. Moreover, in more than a half of young women (54,8%) and men (52,4%) the body mass deficiency was revealed (BMI<18kg/m2). CONCLUSION: Conclusions: The study showed abnormal nutritional behavior of high school youth. Therefore, there is a need to conduct activities under health prevention, which improve the eating habits of young people. PMID- 29786587 TI - Legal protection of public health through control over genetically modified food. AB - OBJECTIVE: Introduction: Science is constantly being developed which leads to both positive and negative changes in public health and the environment. One of the results of scientific progress is introduction of food based on genetically modified organisms whose effects on human health, to date, remain scantily studied and are ambiguous. The aim: to determine how human health can be influenced by food production based on genetically modified organisms. PATIENTS AND METHODS: Materials and methods: international acts, data of international organizations and conclusions of scientists have been examined and used in the study. The article also summarizes information from scientific journals and monographs from a medical and legal point of view with scientific methods. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. CONCLUSION: Conclusions: Genetically modified organisms are specific human-made organisms being a result of using modern biotechnology techniques. They have both positive and negative effects on human health and the environment. The main disadvantage is not sufficient study of them in various spheres of public life. PMID- 29786588 TI - [Infectious complications of prostate biopsy]. AB - Prostate cancer is the second most common malignancy in men in Poland. Prostate biopsy remains the gold standard for diagnosis. Every year, the number of procedures is increasing, so knowledge of possible complications is becoming crucial. Over time, a continuous increase in infectious complications of prostate biopsy is observed, so it is important to identify risk factors and preventive methods. Antibiotic prophylaxis is mandatory for prostate biopsy. Simultaneously, complications after prostate biopsy affect as many as 90% of patients, including up to 17% of infective complications. In some patients, complications are severe and require urgent medical intervention. The risk of death from septic complications is approximately 0.1%. Significant risk factors are diabetes, older age, enlarged prostate gland and recent antibiotic exposure. Transperineal or MRI guided biopsy is associated with a significantly lower incidence of severe infectious complications. PMID- 29786589 TI - Bacterial factors of cariogenicity (literature review). AB - OBJECTIVE: Introduction: According to the 2003 WHO report, dental caries affects from 60% to 90% of school-age children and adults that makes it one of the most common diseases worldwide. The aim was to systematize data about the modern conception of plaque formation and role of microorganisms in its development. PATIENTS AND METHODS: Materials and methods: Biblosemantic, 50 medical literature sources were systematically reviewed as the material for the research. RESULTS: Review: According to Miller's theory, oral microorganisms can decompose dietary carbohydrates into acids, which in turn dissolve the calcium phosphates found in the enamel, causing it demineralisation Along with Streptococcus mutans, nowadays some other bacteria as Streptococcus sorbinus, Lactobacillus spp. and Actinomyces spp. have been well studied as caries contributors. However, the disease is related to plaque-mediated, because a much larger number of normal oral microflora representatives are involved in creating favourable preconditions for its development. There are a lot of original research papers about a role of bacteria in caries decay but compositions and characters of oral microflora are changing nowadays. Therefore, authors show the main cariogenic bacteria and their factors of pathogenicity which create special conditions for caries lesions. Modern concepts of dental plaque formation and pathogenesis of plaque-assosiative diseases are presented according to the new actual dental research. A lot of attention is paid to the biochemical properties of cariogenic bacteria and chemical process in biofilm. Role of acid and alkali production by oral bacteria in caries decay are shown in this article. Moreover, mechanisms of bacterial acid fast and acid-tolerance are presented. CONCLUSION: Conclusions: Analysis of literature demonstrates a lot of bacterial pathogenicity factors which play key role in caries development. PMID- 29786590 TI - Hepatitis c and human rights: comparison of legal experience of Ukraine and Georgia. AB - A comparative legal research of human rights provision in Ukraine and Georgia, in the aspect of combating viral HCV, was conducted. Ukrainian advocacy experience and Georgian strategic litigation experience with regard to human rights and HCV was analyzed. Key international instruments, which lay the conceptual foundations as well as outline the measures, which are directed at human rights in patient care provision and fighting viral hepatitis, were elucidated. Attention was paid to the Global health sector strategy. Viral hepatitis, 2016 - 2021 [1], which, for the first time, defined a global strategy on fighting viral hepatitis, in particular HCV and envisaged the advocacy vectors. The frames of interaction of the human rights in patient care concept and public health, which consists in realization of certain human rights were elucidated and the necessity to embody the human rights in patient care concept into the state policy in the field of public health was determined. It was found out that a common international problem in combating HCV is a deficiency of financial resources, which are necessary for effective fighting the epidemics and guarantee equal access to treatment for every person. The international community outlined five most important spheres, which require investments and will catalyze the measures, which need to be taken in order to fight hepatitis. Analysis of the Ukrainian experience was focused on the issue of donated blood safety and successful advocacy campaigns, which were carried out in order to promote the adoption of programs on prophylactics, diagnostics and treatment of HCV both on national and regional levels. Examples of ensuring the rights of the marginalized groups during HCV treatment, in particular of the people who inject drugs, people living with HIV, participants of the antiterrorist operation were provided. Interesting and important is the experience of Georgia concerning human rights protection in the ECtHR, which has a legal effect for other countries which ratified the Convention for the Protection of Human Rights and Fundamental Freedoms, for instance for Ukraine, where the EctHR judgments are recognized as a source of law. PMID- 29786592 TI - Obstetric and gynecological care by family doctors in ukraine: literature review. AB - OBJECTIVE: Introduction: The analysis of literature on the questions of obstetrical and gynecologic care by general practitioners - family doctors in Ukraine has been presented in the article. Special attention has been paid to the actual problems of primary health care implementation on the basis of family medicine. The aim of the study is to find out the depth of the problem "A female doctor as an obstetrician-gynecologist" by analyzing scientific relevant literature data. PATIENTS AND METHODS: Materials and methods: An analysis of international and national scientific literature on the problem of obstetrical and gynecologic care by general practitioners - family doctors. CONCLUSION: Conclusions: It is evident from the review of negative demographic situation that at present topical are the issues of extension of primary care professionals' functions concerning sexual upbringing, family planning, reproductive health promotion of the population, improvement of the qualification level of doctors on obstetricgynecological assistance issues and creation of a motivation system for primary care physicians, which requires a decision at the national level. PMID- 29786591 TI - [Patient with spine pain and magnetic resonance imaging result]. AB - Degenerative spine disease is a serious social problem. In most cases, it causes pain and neurological symptoms. Most patients are therefore referred for magnetic resonance imaging (MRI). The article discusses the relationship between back pain and magnetic resonance changes. The signification of some of the radiological symptoms remains controversial. Some of them are markers of acute pain, others may be clinically insignificant, occurring with age. Authors presents some of the magnetic resonance alterations and based on the latest articles discusses their clinical significance. The issues of performing routine, control MRI examination due to chronic back pain and the incidence of new radiological findings were also discussed. PMID- 29786593 TI - Reproductive function: the protection of the rights of the people which are sent to the area of the fighting. AB - OBJECTIVE: Introduction: The issues of problems of the legal regulation of posthumous reproduction in Ukraine and foreign countries are analysis in the article. The author substantiates the necessity in the creation and acceptance of the State Program of the retrieval of reproductive cells in people who are sending to the area of the fighting. The aim:the purpose of our work is a comprehensive study of post-mortem (post-mortem) reproduction and substantiation of the possibility and necessity of adopting a state program for the selection of reproductive cells of individuals who are sent to a combat zone to ensure their full social protection and assistance in the realization of the right to fatherhood or motherhood. PATIENTS AND METHODS: Materials and methods: the experience of certain countries is analyzed in the research. Additionally, we used statistical data of international organizations, conclusions of experts and foreign legal acts dealing with posthumous reproduction and auxiliary reproductive technologies, judicial practice, doctrinal ideas and views on this issue. RESULTS: Review: there are medical (practical) preconditions for the introduction of posthumous reproduction programs. Among them is the technology of obtaining reproductive cells (post-mortem too), their preservation and successful subsequent use. In addition, foreign experience shows the success of the application of these technologies and the real guarantee of full implementation of the range of rights to the family, fatherhood or maternity. CONCLUSION: Conclusions: we note the urgent need to develop and adopt a state reproductive cell selection program for individuals who are sent to the combat zones (according to a model that exists in such countries as the USA and Israel). PMID- 29786595 TI - [Genetically determined abnormal electrical activity of the brain and the heart]. AB - Mutations leading to disorders within ion (mainly potassium and sodium) channels, have different degrees of expression in the brain and in the heart, which can cause simultaneous occurrence of disorders in both organs. This is manifested by the occurrence of epileptic seizures and cardiac electrical disturbances, further exacerbated by stimulation of autonomic structures within the central nervous system. In all patients with unclear paroxysmal disorders, and in those with unexplained sudden cardiac death, consideration should be given to the possibility of occurrence of genetically determined disorders in the ion channels. This article concerns the most common genetically determined epilepsy syndromes and genetically determined cardiac diseases. PMID- 29786594 TI - [Brain microbleeds - definition, pathophysiology and the consequences]. AB - Brain microbleeds are defined as small, circular hypointense changes in T2 sequensec of brain MRI, well demarcated from the surrounding tissue. They represent the phagocytized products of blood distribution extravasated from pathologically altered vessels. The echo-T2-dependent gradient (GRE) and magnetic susceptibility testing (SWI) sequences are usually used to visualize them. The pathogenesis of microbleeds very complex but angiopathy associated with arterial hypertension and cerebral amyloid angiopathy play a special role. Atherosclerotic lesions and inflammatory processes are also important. Microbleeds can be found in healthy people as well as in many disorders such as hypertension, Alzheimer's disease or other types of dementia. Their prevalence increases with age. Microbleeds may have a multidimensional effect on the surrounding brain tissue. It is suggested that they disrupt both the brain structure and the electrical function of neurons. In this review article we present current knowledge on the cerebral microbleeds. PMID- 29786596 TI - [Coexistence of asthma and obstructive sleep apnea syndrome - review of the literature]. AB - Both asthma and obstructive sleep apnea (OSA) syndrome are frequent diseases and their coexistence may implicate important consequences. The incidence of OSA syndrome among the patients with asthma is higher than in the general population, especially in the patients with nocturnal symptoms persisting despite treatment, in patients frequently admitted to hospital because of the exacerbations of asthma, and in obese patients. The causes of frequent coexistence of asthma and OSA syndrome are not fully elucidated. The common abnormalities possibly linking asthma and OSA syndrome include obesity, gastro-esophageal reflux, nasal obstruction, and inflammation. In some patients with asthma it would be advised to search for OSA syndrome, as obstructive sleep apneas and hypopneas may influence asthma exacerbations. Especially, OSA should be suspected in the asthma patients with the signs of ventilatory disturbances during sleep. The method of choice of treatment of the patients with OSA syndrome is continuous positive airway pressure (CPAP) applied through the nasal or full-face mask, that leads to elimination of the obstructive sleep apneas and hypopneas during sleep. CPAP treatment may also positively influence the course of asthma. PMID- 29786597 TI - [The sexuality of woman in puerperium]. AB - After the birth various physical, hormonal and psychological changes affect women's emotional status. These significantly impact their family life including the quality of sexual relationships. Among these factors the method of birth, hormonal changes, breast feeding and incidence of postpartal depression are considered to affect relations with the partner. Unfortunately the sexuality in this special time in women's life is commonly avoided or underestimated both by woman and doctors. PMID- 29786598 TI - [Hypertrophic cardiomyopathy: an intraoperative death case analysis and substantiation of the standards of perioperative anesthetic management in a non cardiosurgery clinic]. AB - The article is based on the case analysis of a sudden and unexpected intraoperative death of a 51-year-old female patient with hypertrophic cardiomyopathy, who was undergoing a non-cardiac operation in a non-cardiosurgery clinic, from acute precipitation of left ventricular outflow tract obstruction provoked by surgery and anesthesia. It emphasizes the importance of raising non cardiac anesthesiologists' awareness of the issue and having clear standards of pre-operative evaluation and perioperative management of patients with hypertrophic cardiomyopathy in order to avoid fatal medical errors. A literature review on the disease with an accent on anesthesia-related issues is also given, and four standards of perioperative anesthetic management of patients with hypertrophic cardiomyopathy presenting for non-cardiac surgery in general hospital settings are developed and offered. PMID- 29786600 TI - Shock synthesis and characterization of titanium dioxide with alpha-PbO2 structure. AB - The phase transformation behavior of anatase and rutile titanium dioxide with particle sizes of 60 nm and 150 nm under shock compression have been investigated. To increase the shock pressure and reduce the shock temperature, copper powder and a small amount of paraffin were mixed with the TiO2 powder. The shock recovered samples were characterized by x-ray diffraction, Raman spectroscopy, and transmission electron microscope. The results indicate that both anatase and rutile TiO2 can transform to alpha-PbO2 phase TiO2 through shock induced phase transition. The transformation rate of alpha-PbO2 phase TiO2 for anatase TiO2 under shock compression is 100% and pure alpha-PbO2 phase TiO2 can be obtained, while the transformation rate for rutile TiO2 is over 90%. The influence of the particle size on the yield of alpha-PbO2 phase TiO2 is not noticeable. The thermal stability of the recovered pure alpha-PbO2 phase TiO2 was characterized by high temperature x-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The results show that alpha-PbO2 phase TiO2 transforms to rutile TiO2 when heated to temperature higher than 560 degrees C. The mechanisms of the phase transition of TiO2 under shock compression are discussed. PMID- 29786601 TI - Heterogeneous photocatalysis and its potential applications in water and wastewater treatment: a review. AB - There has been a considerable amount of research in the development of sustainable water treatment techniques capable of improving the quality of water. Unavailability of drinkable water is a crucial issue especially in regions where conventional drinking water treatment systems fail to eradicate aquatic pathogens, toxic metal ions and industrial waste. The research and development in this area have given rise to a new class of processes called advanced oxidation processes, particularly in the form of heterogeneous photocatalysis, which converts photon energy into chemical energy. Advances in nanotechnology have improved the ability to develop and specifically tailor the properties of photocatalytic materials used in this area. This paper discusses many of those photocatalytic nanomaterials, both metal-based and metal-free, which have been studied for water and waste water purification and treatment in recent years. It also discusses the design and performance of the recently studied photocatalytic reactors, along with the recent advancements in the visible-light photocatalysis. Additionally, the effects of the fundamental parameters such as temperature, pH, catalyst-loading and reaction time have also been reviewed. Moreover, different techniques that can increase the photocatalytic efficiency as well as recyclability have been systematically presented, followed by a discussion on the photocatalytic treatment of actual wastewater samples and the future challenges associated with it. PMID- 29786599 TI - [A complex clinical case of polyarteritis nodosa through the prism of kidneys]. AB - Polyarteritis nodosa is a chronic systemic vasculitis, characterized by the autoimmune, necrotising lesion of the walls of the small- and medium-bore visceral and peripheral arteries, resulting in vessel aneurysms and the secondary degeneration of organs and systems. All types of vessels (arteries, veins, capillaries) can be affected or, alternatively, the process can be limited predominantly to the vessels of one system, the clinical symptoms depending on the bore and location of the affected vessels. Varying degrees of the lesion, varying combinations and sequencing, the compensation abilities of the vessel disorders can blur the clinical picture, even though early pathomorphological changes are quite pronounced. The article presents the clinical case of a later stage of polyarteritis nodosa, which demonstrates the polymorphism of clinical symptoms and the necessity of applying modern diagnostic methods and a timely treatment with a view to reducing the frequency of fatal outcomes. PMID- 29786602 TI - Microfluidic system for modelling 3D tumour invasion into surrounding stroma and drug screening. AB - Tumour invasion into the surrounding stroma is a critical step in metastasis, and it is necessary to clarify the role of microenvironmental factors in tumour invasion. We present a microfluidic system that simulated and controlled multi factors of the tumour microenvironment for three-dimensional (3D) assessment of tumour invasion into the stroma. The simultaneous, precise and continuous arrangement of two 3D matrices was visualised to observe the migration of cancer cell populations or single cells by transfecting cells with a fluorescent protein. A vascular endothelial layer was formed to simulate transendothelial transport of nutrients, and its endothelial barrier function was verified by the diffusion of 70 kDa fluorescein isothiocyanate (FITC)-Dextran in 3D matrices. Through high-throughput cell migration tracking observation and statistic evaluation, we clarified that cell density of the tumour directly determined its invasiveness. The results suggested that increased secretion of IL-6 among both cancer cells (MDA-MB-231) and noncancerous cells (MCF-10A or HDF-n) after co culture contributes to cancer cell invasiveness, and this was verified by an IL-6 inhibitor assay. Finally, the drug efficacy of paclitaxel was reflected as changes in cancer cell migration ability, viability, and morphology. Together, our microfluidic devices could be a useful tool to study the mechanism of tumour invasion into the stroma and to screen anti-metastatic drugs. PMID- 29786603 TI - Natural levels of polonium-210 in urine. AB - This paper presents a review and analysis of available data on background levels of polonium-210 in urine. It was established that 819 measurements could be considered to correspond to natural background levels, excluding a large number of values identified by the original investigators as potentially due to an artificial source or due to recognised enhancement of dietary intake. Almost 550 measurements were extracted from studies reported in the literature; additional measurements were contributions of previously unpublished data by authors of more recent papers. The majority of the measurements (462) were single samples from individuals but 357 values were repeat measurements provided by 81 subjects and for these the mean value for each subject was used. The final dataset consisted of measurements from 543 individuals. Analysis of the measurements confirmed the data was log normally distributed with mean and median values of 15.5 mBq d-1 and 11 mBq d-1 in urine samples, respectively. While the overall range was from 0.3 111 mBq d-1, almost 90% of the measurements were less than 30 mBq d-1, 95% were less than 45 mBq d-1, and 99% less than 70 mBq d-1. Separate analysis of data for smokers and non-smokers suggested a modest increase in smokers of up to 5 mBq d 1. Perhaps reflecting the importance of dietary differences such as seafood consumption, a marked difference between countries was observed in the range of results. While for most countries, 95% or more of results were below 30 mBq d-1, China and Italy were notable exceptions, with greater than 20% of values above this level. PMID- 29786604 TI - Size, shape, and compositional effects on the order-disorder phase transitions in Au-Cu and Pt-M (M = Fe, Co, and Ni) nanocluster alloys. AB - Au-Cu and Pt-M (M = Fe, Co, and Ni) nanocluster alloys are currently being investigated world-wide by many researchers for their interesting catalytic and nanophase properties. The low temperature behavior of the phase diagrams is not well understood for alloys with nanometer sizes and shapes. We consider two models for low temperature ordering in the phase diagrams of Au-Cu and Pt-M nanocluster alloys. These models are valid for sizes ~5 nm and approach bulk values for sizes ~20 nm. We study the phase transitions in nanoclusters with cubic, octahedral, and cuboctahedral shapes, covering the compositions of interest. These models are based on studying the melting temperatures in nanoclusters using the regular solution, mixing model for alloys. From our data, experiments on nanocubes about 5 nm in size, of stoichiometric AuCu and PtM composition, could help differentiate between the models. Dispersion data shows that for the three shapes considered, octahedra have the highest percentage of surface atoms for the same relative diameter. We summarize the effects of structural ordering on the catalytic activity and suggest a method to avoid sintering during annealing of Pt-M alloys. PMID- 29786605 TI - Hydrophobic interaction mediated coating of pluronics on mesoporous silica nanoparticle with stimuli responsiveness for cancer therapy. AB - In this research, a novel method was used to successfully stably coat Pluronic P123 on mesoporous silica nanoparticles (MSNs). Co-constructing a drug delivery system (DDS) with P123 and MSNs has not been previously reported. In this DDS, the coating of P123 was realized through a hydrophobic interaction with octadecyl chain-modified MSNs. The experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segments could keep the nanoassemblies stable. For comparison, nanoassemblies consisting of P123 and octadecyl chain modified MSNs with or without a disulfide bond were prepared, which were denoted as PSMSNs and PMSNs, respectively. The disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decreasing the toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with the PMSNs, PSMSNs displayed a redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, the cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in the tumor was enhanced after coating the MSNs by virtue of the 'EPR' effect of nanoparticles compared with the solution form. PMID- 29786606 TI - Crystal and magnetic structure of antiferromagnetic Mn2PtPd. AB - We have investigated the crystal and magnetic structure of Mn2PtPd alloy using powder x-ray and neutron diffraction experiments. This compound is believed to belong to the Heusler family having crystal symmetry I4/mmm (TiAl3-type). However, in this work we found that the Pd and Pt atoms are disordered and thus Mn2PtPd crystallizes in the L10 structure having P4/mmm symmetry (CuAu-I type) like MnPt and MnPd binary alloys. The lattice constants are a = 2.86 A and c = 3.62 A at room temperature. Mn2PtPd has a collinear antiferromagnetic spin structure below the Neel temperature T N = 866 K, where Mn moments of ~4 u B lie in the ab-plane. We observed a strong change in the lattice parameters near T N. The sample exhibits metallic behaviour, where electrical resistivity and carrier concentration are of the order of 10-5 Omega cm and 1021 cm-3, respectively. PMID- 29786607 TI - Pre-set extrusion bioprinting for multiscale heterogeneous tissue structure fabrication. AB - Recent advances in three-dimensional bioprinting technology have led to various attempts in fabricating human tissue-like structures. However, current bioprinting technologies have limitations for creating native tissue-like structures. To resolve these issues, we developed a new pre-set extrusion bioprinting technique that can create heterogeneous, multicellular, and multimaterial structures simultaneously. The key to this ability lies in the use of a precursor cartridge that can stably preserve a multimaterial with a pre defined configuration that can be simply embedded in a syringe-based printer head. The multimaterial can be printed and miniaturized through a micro-nozzle without conspicuous deformation according to the pre-defined configuration of the precursor cartridge. Using this system, we fabricated heterogeneous tissue-like structures such as spinal cords, hepatic lobule, blood vessels, and capillaries. We further obtained a heterogeneous patterned model that embeds HepG2 cells with endothelial cells in a hepatic lobule-like structure. In comparison with homogeneous and heterogeneous cell printing, the heterogeneous patterned model showed a well-organized hepatic lobule structure and higher enzyme activity of CYP3A4. Therefore, this pre-set extrusion bioprinting method could be widely used in the fabrication of a variety of artificial and functional tissues or organs. PMID- 29786608 TI - Microscopic aspects of wetting using classical density functional theory. AB - Wetting is a rather efficient mechanism for nucleation of a phase (typically liquid) on the interface between two other phases (typically solid and gas). In many experimentally accessible cases of wetting, the interplay between the substrate structure, and the fluid-fluid and fluid-substrate intermolecular interactions brings about an entire 'zoo' of possible fluid configurations, such as liquid films with a thickness of a few nanometers, liquid nanodrops and liquid bridges. These fluid configurations are often associated with phase transitions occurring at the solid-gas interface and at lengths of just several molecular diameters away from the substrate. In this special issue article, we demonstrate how a fully microscopic classical density-functional framework can be applied to the efficient, rational and systematic exploration of the rich phase space of wetting phenomena. We consider a number of model prototype systems such as wetting on a planar wall, a chemically patterned wall and a wedge. Through density-functional computations we demonstrate that for these simply structured substrates the behaviour of the solid-gas interface is already highly complex and non-trivial. PMID- 29786610 TI - Thermoelectric transport properties of Ti doped/adsorbed monolayer blue phosphorene. AB - Thermoelectric transport properties of Ti doped or adsorbed monolayer blue phosphorene are investigated by density functional theory combined with the nonequilibrium Green's function formalism. The thermal giant magnetoresistance and a nearly 100% spin polarization which solely relies on the temperature gradient of electrodes without bias or gate voltage are observed. Moreover, the spin Seebeck effect is also found. Furthermore, taking into account the electronic and phonon dispersion, the thermoelectric merit for Ti doping in the monolayer blue phosphorene at room temperature is also studied, the maximum value of thermoelectric merit can reach 1.01 near the Fermi level. The results indicate that Ti doped or adsorbed monolayer blue phosphorene has potential application in both spintronics and spin caloritronics. PMID- 29786609 TI - Comparison of trapped charges and hysteresis behavior in hBN encapsulated single MoS2 flake based field effect transistors on SiO2 and hBN substrates. AB - Molybdenum disulfide (MoS2) based field effect transistors (FETs) are of considerable interest in electronic and opto-electronic applications but often have large hysteresis and threshold voltage instabilities. In this study, by using advanced transfer techniques, hexagonal boron nitride (hBN) encapsulated FETs based on a single, homogeneous and atomic-thin MoS2 flake are fabricated on hBN and SiO2 substrates. This allows for a better and a precise comparison between the charge traps at the semiconductor-dielectric interfaces at MoS2-SiO2 and hBN interfaces. The impact of ambient environment and entities on hysteresis is minimized by encapsulating the active MoS2 layer with a single hBN on both the devices. The device to device variations induced by different MoS2 layer is also eliminated by employing a single MoS2 layer for fabricating both devices. After eliminating these additional factors which induce variation in the device characteristics, it is found from the measurements that the trapped charge density is reduced to 1.9 * 1011 cm-2 on hBN substrate as compared to 1.1 * 1012 cm-2 on SiO2 substrate. Further, reduced hysteresis and stable threshold voltage are observed on hBN substrate and their dependence on gate sweep rate, sweep range, and gate stress is also studied. This precise comparison between encapsulated devices on SiO2 and hBN substrates further demonstrate the requirement of hBN substrate and encapsulation for improved and stable performance of MoS2 FETs. PMID- 29786611 TI - Increased accuracy of planning tools for optimization of dynamic multileaf collimator delivery of radiotherapy through reformulated objective functions. AB - The purpose of this study is to examine in a clinical setting a novel formulation of objective functions for intensity-modulated radiotherapy treatment plan multicriteria optimization (MCO) that we suggested in a recent study. The proposed objective functions are extended with dynamic multileaf collimator (DMLC) delivery constraints from the literature, and a tailored interior point method is described to efficiently solve the resulting optimization formulation. In a numerical planning study involving three patient cases, DMLC plans Pareto optimal to the MCO formulation with the proposed objective functions are generated. Evaluated based on pre-defined plan quality indices, these DMLC plans are compared to conventionally generated DMLC plans. Comparable or superior plan quality is observed. Supported by these results, the proposed objective functions are argued to have a potential to streamline the planning process, since they are designed to overcome the methodological shortcomings associated with the conventional penalty-based objective functions assumed to cause the current need for time-consuming trial-and-error parameter tuning. In particular, the increased accuracy of the planning tools imposed by the proposed objective functions has the potential to make the planning process less complicated. These conclusions position the proposed formulation as an alternative to existing methods for automated planning. PMID- 29786612 TI - A formalism for reference dosimetry in photon beams in the presence of a magnetic field. AB - A generic formalism is proposed for reference dosimetry in the presence of a magnetic field. Besides the regular correction factors from the conventional reference dosimetry formalisms, two factors are used to take into account magnetic field effects: (1) a dose conversion factor to correct for the change in local dose distribution and (2) a correction of the reading of the dosimeter used for the reference dosimetry measurements. The formalism was applied to the Elekta MRI-Linac, for which the 1.5 T magnetic field is orthogonal to the 7 MV photon beam. For this setup at reference conditions it was shown that the dose decreases with increasing magnetic field strength. The reduction in local dose for a 1.5 T transverse field, compared to no field is 0.51% +/- 0.03% at the reference point of 10 cm depth. The effect of the magnetic field on the reading of the dosimeter was measured for two waterproof ionization chambers types (PTW 30013 and IBA FC65-G) before and after multiple ramp-up and ramp-downs of the magnetic field. The chambers were aligned perpendicular and parallel to the magnetic field. The corrections of the readings of the perpendicularly aligned chambers were 0.967 +/- 0.002 and 0.957 +/- 0.002 for respectively the PTW and IBA ionization chambers. In the parallel alignment the corrections were small; 0.997 +/- 0.001 and 1.002 +/- 0.003 for the PTW and IBA chamber respectively. The change in reading due to the magnetic field can be measured by individual departments. The proposed formalism can be used to determine the correction factors needed to establish the absorbed dose in a magnetic field. It requires Monte Carlo simulations of the local dose and measurements of the response of the dosimeter. The formalism was successfully implemented for the MRI-Linac and is applicable for other field strengths and geometries. PMID- 29786615 TI - Morphological control of gold nanorods via thermally driven bi-surfactant growth and application for detection of heavy metal ions. AB - We report a modified synthesis route of colloidal gold nanorods (AuNRs) by combining the thermal re-shaping treatment and bi-surfactant modification using hexadecyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL). Aspect ratios down to 1.3 +/- 0.1 can be achieved in addition to good monodispersity, uniformity, and chemical stability of the materials. Furthermore, without needing post-treatment, metal ions directly interact with the AuNRs efficiently, allowing rapid and sensitive colorimetric detection of heavy metal ions such as Pb2+ and Cu2+ with a low concentration down to 2.5 MUM. The detection performance in terms of selectivity, sensitivity and stability is systematically evaluated. The AuNRs with tunable aspect ratios as well as chemical stability have potential in surface-plasmon-based applications such as biochemical sensing, biochemical imaging, medical diagnostics, and cancer therapy. PMID- 29786614 TI - A novel optimization framework for VMAT with dynamic gantry couch rotation. AB - Existing volumetric modulated arc therapy (VMAT) optimization using coplanar arcs is highly efficient but usually dosimetrically inferior to intensity modulated radiation therapy (IMRT) with optimized non-coplanar beams. To achieve both dosimetric quality and delivery efficiency, we proposed in this study, a novel integrated optimization method for non-coplanar VMAT (4piVMAT). 4piVMAT with direct aperture optimization (DAO) was achieved by utilizing a least square dose fidelity objective, along with an anisotropic total variation term for regularizing the fluence smoothness, a single segment term for imposing simple apertures, and a group sparsity term for selecting beam angles. Continuous gantry/couch angle trajectories were selected using the Dijkstra's algorithm, where the edge and node costs were determined based on the maximal gantry rotation speed and the estimated fluence map at the current iteration, respectively. The couch-gantry-patient collision space was calculated based on actual machine geometry and a human subject 3D surface. Beams leading to collision are excluded from the DAO and beam trajectory selection (BTS). An alternating optimization strategy was implemented to solve the integrated DAO and BTS problem. The feasibility of 4piVMAT using one full-arc or two full-arcs was tested on nine patients with brain, lung, or prostate cancer. The plan was compared against a coplanar VMAT (2piVMAT) plan using one additional arc and collimator rotation. Compared to 2piVMAT, 4piVMAT reduced the average maximum and mean organs-at-risk dose by 9.63% and 3.08% of the prescription dose with the same target coverage. R50 was reduced by 23.0%. Maximum doses to the dose limiting organs, such as the brainstem, the major vessels, and the proximal bronchus, were reduced by 8.1 Gy (64.8%), 16.3 Gy (41.5%), and 19.83 Gy (55.5%), respectively. The novel 4piVMAT approach affords efficient delivery of non coplanar arc trajectories that lead to dosimetric improvements compared with coplanar VMAT using more arcs. PMID- 29786616 TI - Derivation of new diagnostic reference levels for neuro-paediatric computed tomography examinations in Switzerland. AB - PURPOSE: Definition of new national diagnostic reference levels (DRLs) for volume computed tomography dose index (CTDIvol) and dose length product (DLP) for neuro paediatric CT examinations depending on the medical indication. METHODS: Paediatric cranial CT data sets acquired between January 2013 and December 2016 were retrospectively collected between July 2016 and March 2017 from eight of the largest university and cantonal hospitals that perform most of the neuro paediatric CTs in Switzerland. A consensus review of CTDIvol and DLP was undertaken for three defined anatomical regions: brain, facial bone, and petrous bone, each with and without contrast medium application. All indications for cranial CT imaging in paediatrics were assigned to one of these three regions. Descriptive statistical analysis of the distribution of the median values for CTDIvol and DLP yielded values in the minimum, maximum, 25th percentile (1st quartile), median (2nd quartile), and 75th percentile (3rd quartile). New DRLs for neuro-paediatric CT examinations in Switzerland were based on the 75th percentiles of the distributions of the median values of all eight centres. Where appropriate, values were rounded such that the DRLs increase or at least remain constant as the age of the patient increases. RESULTS: Our results revealed DRLs for CTDIvol and DLP up to 20% lower than the DRLs used so far in Switzerland and elsewhere in Europe. CONCLUSIONS: This study provides Swiss neuro-paediatric CT DRL values to establish optimum conditions for paediatric cranial CT examinations. Periodic national updates of DRLs, following international comparisons, are essential. PMID- 29786617 TI - Fabrication of hollow boron-doped diamond nanostructure via electrochemical corrosion of a tungsten oxide template. AB - In the study, a hollow boron-doped diamond (BDD) nanostructure electrode is fabricated to increase the reactive surface area for electrochemical applications. Tungsten oxide nanorods are deposited on the silicon substrate as a template by the hot filament chemical vapor deposition (HFCVD) method. The template is coated with a 100 nm BDD layer deposited by HFCVD to form a core shell nanostructure. The WO x core is finally electrochemically dissolved to form hollow BDD nanostructure. The fabricated hollow BDD nanostructure electrode is investigated via scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The specific surface areas of the electrodes were analyzed and compared by using Brunauer-Emmett-Teller method. Furthermore, cyclic voltammetry and chronocoulometry are used to investigate the electrochemical characteristics and the reactive surface area of the as-prepared hollow BDD nanostructure electrode. A hollow BDD nanostructure electrode exhibits a reactive area that is 15 times that of a planar BDD thin electrode. PMID- 29786618 TI - Acoustic performance of dual-electrode electrostatic sound generators based on CVD graphene on polyimide film. AB - We investigated the acoustic performance of electrostatic sound-generating devices consisting of bi-layer graphene on polyimide film. The total sound pressure level (SPL) of the sound generated from the devices was measured as a function of source frequency by sweeping, and frequency spectra were measured at 1/3 octave band frequencies. The relationship between various operation conditions and total SPL was determined. In addition, the effects of changing voltage level, adding a DC offset, and using two pairs of electrodes were evaluated. It should be noted that two pairs of electrode operations improved sound generation by about 10 dB over all frequency ranges compared with conventional operation. As for the sound-generating capability, total SPL was 70 dBA at 4 kHz when an AC voltage of 100 Vpp was applied with a DC offset of 100 V. Acoustic characteristics differed from other types of graphene-based sound generators, such as graphene thermoacoustic devices and graphene polyvinylidene fluoride devices. The effects of diameter and distance between electrodes were also studied, and we found that diameter greatly influenced the frequency response. We anticipate that the design information provided in this paper, in addition to describing key parameters of electrostatic sound-generating devices, will facilitate the commercial development of electrostatic sound-generating systems. PMID- 29786613 TI - Biophysics of membrane curvature remodeling at molecular and mesoscopic lengthscales. AB - At the micron scale, where cell organelles display an amazing complexity in their shape and organization, the physical properties of a biological membrane can be better-understood using continuum models subject to thermal (stochastic) undulations. Yet, the chief orchestrators of these complex and intriguing shapes are a specialized class of membrane associating often peripheral proteins called curvature remodeling proteins (CRPs) that operate at the molecular level through specific protein-lipid interactions. We review multiscale methodologies to model these systems at the molecular as well as at the mesoscopic and cellular scales, and also present a free energy perspective of membrane remodeling through the organization and assembly of CRPs. We discuss the morphological space of nearly planar to highly curved membranes, methods to include thermal fluctuations, and review studies that model such proteins as curvature fields to describe the emergent curved morphologies. We also discuss several mesoscale models applied to a variety of cellular processes, where the phenomenological parameters (such as curvature field strength) are often mapped to models of real systems based on molecular simulations. Much insight can be gained from the calculation of free energies of membranes states with protein fields, which enable accurate mapping of the state and parameter values at which the membrane undergoes morphological transformations such as vesiculation or tubulation. By tuning the strength, anisotropy, and spatial organization of the curvature-field, one can generate a rich array of membrane morphologies that are highly relevant to shapes of several cellular organelles. We review applications of these models to budding of vesicles commonly seen in cellular signaling and trafficking processes such as clathrin mediated endocytosis, sorting by the ESCRT protein complexes, and cellular exocytosis regulated by the exocyst complex. We discuss future prospects where such models can be combined with other models for cytoskeletal assembly, and discuss their role in understanding the effects of cell membrane tension and the mechanics of the extracellular microenvironment on cellular processes. PMID- 29786620 TI - The effect of the bottom electrode on ferroelectric tunnel junctions based on CMOS-compatible HfO2. AB - Ferroelectric tunnel junctions (FTJs) have attracted research interest as promising candidates for non-destructive readout non-volatile memories. Unlike conventional perovskite FTJs, hafnia FTJs offer many advantages in terms of scalability and CMOS compatibility. However, so far, hafnia FTJs have shown poor endurance and relatively low resistance ratios and these have remained issues for real device applications. In our study, we fabricated HfZrO(HZO)-based FTJs with various electrodes (TiN, Si, SiGe, Ge) and improved the memory performance of HZO based FTJs by using the asymmetry of the charge screening lengths of the electrodes. For the HZO-based FTJ with a Ge substrate, the effective barrier afforded by this FTJ can be electrically modulated because of the space charge limited region formed at the ferroelectric/semiconductor interface. The optimized HZO-based FTJ with a Ge bottom electrode presents excellent ferroelectricity with a high remnant polarization of 18 MUC cm-2, high tunneling electroresistance value of 30, good retention at 85 degrees C and high endurance of 107. The results demonstrate the great potential of HfO2-based FTJs in non-destructive readout non-volatile memories. PMID- 29786619 TI - In situ NAP-XPS spectroscopy during methane dry reforming on ZrO2/Pt(1 1 1) inverse model catalyst. AB - Due to the need of sustainable energy sources, methane dry reforming is a useful reaction for conversion of the greenhouse gases CH4 and CO2 to synthesis gas (CO + H2). Syngas is the basis for a wide range of commodity chemicals and can be utilized for fuel production via Fischer-Tropsch synthesis. The current study focuses on spectroscopic investigations of the surface and reaction properties of a ZrO2/Pt inverse model catalyst, i.e. ZrO2 particles (islands) grown on a Pt(1 1 1) single crystal, with emphasis on in situ near ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) during MDR reaction. In comparison to technological systems, model catalysts facilitate characterization of the surface (oxidation) state, surface adsorbates, and the role of the metal-support interface. Using XPS and infrared reflection absorption spectroscopy we demonstrated that under reducing conditions (UHV or CH4) the ZrO2 particles transformed to an ultrathin ZrO2 film that started to cover (wet) the Pt surface in an SMSI-like fashion, paralleled by a decrease in surface/interface oxygen. In contrast, (more oxidizing) dry reforming conditions with a 1:1 ratio of CH4 and CO2 were stabilizing the ZrO2 particles on the model catalyst surface (or were even reversing the strong metal support interaction (SMSI) effect), as revealed by in situ XPS. Carbon deposits resulting from CH4 dissociation were easily removed by CO2 or by switching to dry reforming conditions (673-873 K). Thus, at these temperatures the active Pt surface remained free of carbon deposits, also preserving the ZrO2/Pt interface. PMID- 29786621 TI - A Resisted Sprint Improves Rate of Force Development During a 20-m Sprint in Athletes. AB - Mangine, GT, Huet, K, Williamson, C, Bechke, E, Serafini, P, Bender, D, Hudy, J, and Townsend, J. A resisted sprint improves rate of force development during a 20 m sprint in athletes. J Strength Cond Res 32(6): 1531-1537, 2018-This study examined the effect of a resisted sprint on 20-m sprinting kinetics. After a standardized warm-up, 23 (male = 10, female = 13) Division I basketball players completed 3 maximal 20-m sprint trials while tethered to a robotic resistance device. The first sprint (S1) used the minimal, necessary resistance (1 kg) to detect peak (PK) and average (AVG) sprinting power (P), velocity (V), and force (F); peak rate of force production (RFD) was also calculated. The second sprint (S2) was completed against a load equal to approximately 5% of the athlete's body mass. Minimal resistance (1 kg) was again used for the final sprint (S3). Approximately 4-9 minutes of rest was allotted between each sprint. Separate analyses of variance with repeated measures revealed significant (p <= 0.05) main effects for all sprinting kinetic measures except VPK (p = 0.067). Compared with S1, increased (p < 0.006) 20-m sprint time (3.4 +/- 4.9%), PAVG (115.9 +/- 33.2%), PPK (65.7 +/- 23.7%), FAVG (134.1 +/- 34.5%), FPK (65.3 +/- 16.2%), and RFD (71.8 +/- 22.2%) along with decreased (p < 0.001) stride length (-21 +/- 15.3%) and VAVG (-6.6 +/- 4.6%) were observed during S2. During S3, only RFD was improved (5.2 +/- 7.1%, p < 0.001) compared with S1. In conclusion, completing a short, resisted sprint with a load equating to 5% of body mass before a short sprint (~20-meters) does not seem to affect sprinting time or kinetics. However, it does appear to enhance RFD. PMID- 29786622 TI - Quantitative Analysis of Proximal and Distal Kinetic Chain Musculature During Dynamic Exercises. AB - Oliver, GD, Washington, JK, Barfield, JW, Gascon, SS, and Gilmer, G. Quantitative analysis of proximal and distal kinetic chain musculature during dynamic exercises. J Strength Cond Res 32(6): 1545-1553, 2018-Proximal to distal sequencing for the dynamic movement of throwing is dependent on the movement and stability of the lumbopelvic-hip complex (LPHC) and scapula. Although the need for proximal stability for distal mobility has been vastly documented, pre throwing programs tend to focus on the traditional rotator cuff activation exercises before long toss. Thus, it was the purpose of this study to describe muscle activations of LPHC stabilizing musculature (bilateral gluteus medius and maximus) and scapular stabilizing musculature (dominant side latissimus dorsi, lower trapezius, upper trapezius, and serratus anterior) during 5 kinetic chain exercises that could be implemented in a throwing program. It was hypothesized that both the LPHC and the scapular stabilizing musculature would exhibit moderate to high activation during all the selected kinetic chain exercises. Nineteen healthy college students (23.2 +/- 7.2 years; 176.7 +/- 17.9 cm; 78.0 +/ 28.6 kg) participated. Surface electromyography was used to measure muscle activity in the LPHC and scapular stabilizing musculature during 5 kinetic chain exercises. A nonparametric Friedman test revealed significantly different muscle activations as a factor of exercise for each muscle, chi(18) = 417.220, p < 0.001. The 5 kinetic chain exercises successfully elicited moderate to high muscle activation in all musculature, except the upper trapezius. Because greater muscle activation of the LPHC and scapular stabilizers are crucial during a throwing task, these exercises are recommended for pre-throwing program implementation because they efficiently prepare the stabilizing musculature for lengthy or strenuous throwing tasks, resulting in a potential decrease in injury susceptibility. PMID- 29786623 TI - Rating of Perceived Exertion as a Method of Volume Autoregulation Within a Periodized Program. AB - Helms, ER, Cross, MR, Brown, SR, Storey, A, Cronin, J, and Zourdos, MC. Rating of perceived exertion as a method of volume autoregulation within a periodized program. J Strength Cond Res 32(6): 1627-1636, 2018-The purpose of this investigation was to observe how a rating of perceived exertion (RPE)-based autoregulation strategy impacted volume performed by powerlifters. Twelve (26 +/- 7 years, n = 9 men, n = 3 women) nationally qualified powerlifters performed the back squat, bench press, and deadlift 3x per week on nonconsecutive days in a session order of hypertrophy, power, and then strength; for 3 weeks. Each session subjects performed an initial top set for a prescribed number of repetitions at a target RPE. A second top set was performed if the RPE score was too low, then subsequent back-off sets at a reduced load were performed for the same number of repetitions. When the prescribed RPE was reached or exceeded, sets stopped; known as an "RPE stop." The percentage load reduction for back-off sets changed weekly: there were 2, 4, or 6% RPE stop reductions from the top set. The order in which RPE stop weeks were performed was counterbalanced among subjects. Weekly combined relative volume load (squat + bench press + deadlift), expressed as sets x repetitions x percentage 1-repetition maximum was different between weeks (p < 0.001): 2% = 74.6 +/- 22.3; 4% = 88.4 +/- 23.8; 6% = 114.4 +/- 33.4. Combined weekly bench press volume (hypertrophy + power + strength) was significantly higher in accordance with load reduction magnitude (2% > 4% > 6%; p <= 0.05), combined squat volume was greater in 6 vs. 2% (p <= 0.05), and combined deadlift volume was greater in 6 vs. 2% and 4% (p <= 0.05). Therefore, it does seem that volume can be effectively autoregulated using RPE stops as a method to dictate number of sets performed. PMID- 29786624 TI - Relationship Between Dryland Strength and Swimming Performance: Pull-Up Mechanics as a Predictor of Swimming Speed. AB - Perez-Olea, JI, Valenzuela, PL, Aponte, C, and Izquierdo, M. Relationship between dryland strength and swimming performance: pull-up mechanics as a predictor of swimming speed. J Strength Cond Res 32(6): 1637-1642, 2018-This study aimed to examine the validity of the countermovement jump (CMJ) and the pull-up exercise as predictors of swimming performance. Twelve young male swimmers (Mean +/- SD, 19 +/- 3 years; 75 +/- 10 kg; 180 +/- 6 cm) with a homogenous level of performance (50-m freestyle time [50F]: 26.41 +/- 1.44 seconds, coefficient of variance: 5.5%) participated in this study. Subjects performed a test of a single pull-up (PU) and a test of maximum number of pull-ups until muscular failure (PUF), and the mechanics of the ascending phase were recorded using a lineal force transducer. The height reached in a single CMJ test and the mean height during 30 consecutive CMJs were also determined. The swimmers' 50-m leg-only swimming time (50L) was also registered. The 50F time was strongly correlated with different variables of the PU (r = -0.76 to -0.80; p <= 0.05) and PUF test (r = -0.64 to -0.88; p <= 0.05), but not with the number of pull-ups performed. A significant relationship between 50F and 50L was observed (r = 0.78; p <= 0.05), with no relationship between the CMJ tests and swimming performance. Furthermore, multiple linear regression showed that 50L and the relative loss of velocity during the PUF test accounted for 84% (p < 0.001) of the 50F performance variance. This study shows the validity of the analysis of pull-up mechanics and 50L to predict short-distance swimming performance in trained swimmers, confirming the importance of upper-limb strength and leg kick on this sport. PMID- 29786625 TI - Differences in Glenohumeral Joint Rotation and Peak Power Output Between Super League and Championship Rugby League Players. AB - Haines, MR. Differences in glenohumeral joint rotation and peak power output between Super League and Championship Rugby League players. J Strength Cond Res 32(6): 1685-1691, 2018-Rugby league is a high-intensity sport with large impact forces sustained during play, resulting in high prevalence of shoulder injury. Consequently, shoulder strength and player power are important considerations for injury prevention and performance. Additionally, professional teams regularly compete against semiprofessional teams, where differences in physical conditioning could be marked. The aim of this study was to test for differences in glenohumeral joint rotation and peak power between a professional Super League (SL) and semiprofessional Rugby League Championship (RLC) teams. A cross sectional analysis was used to test 25 SL and 24 RLC players during preseason training. Isokinetic dynamometry, at 240 degrees .s for concentric and eccentric actions was used to assess glenohumeral rotation. Peak power was determined using a maximal 30-second cycle ergometer test. Selective muscular development of the internal rotators without concomitant external rotator strength was evident in the SL team but not the RLC team. Internal rotation peak torque was higher for the SL club for concentric (~24%) and eccentric (~16%) muscle actions (p <= 0.05), and this contributed to a lower ipsilateral reciprocal muscle group ratio (external to internal concentric) for the SL team compared with the RLC team (~47% and ~60% respectively; p <= 0.05). Peak power output was also higher for the SL team (1,409 +/- 153 vs. 1,273 +/- 159 W; p <= 0.05). The results highlight a mismatch in the physical conditioning of SL and RLC players with implications for practitioners to design strength and conditioning programs that minimize the risk of injury while optimizing performance. PMID- 29786626 TI - Observation of Women Soccer Players' Physiology During a Single Season. AB - Paulsen, KM, Butts, CL, and McDermott, BP. Observation of women soccer players' physiology during a single season. J Strength Cond Res 32(6): 1702-1707, 2018-The purpose of this study was to observe heart rate (HR) responses in match settings over the course of a conference season in National Collegiate Athletic Association Division I women's soccer. Twenty-one female collegiate soccer players were provided a HR monitor and instructed to wear it for the duration of match play. Player positions included 6 defenders (DEF), 6 midfielders (MID), and 9 forwards (FWD). Defenders were further identified as either center defenders (CD) or outside defenders (OD). A 1-way analysis of variance was used to determine if mean HR varied between FWD, MID, and DEF. An independent t-test was used to determine if there was a difference between CD and OD HRs. The FWD, MID, and DEF did have significantly different mean HR (p <= 0.05), but post-hoc analysis revealed no significant differences (p >= 0.05). However, CD demonstrated significantly lower HRs than OD (p = 0.009). Player position, specifically in the CD and OD role, impact the intensity of exercise in match settings and may be used to specify training and conditioning sessions. PMID- 29786628 TI - Influence of Team's Rank on Soccer Referees' External and Internal Match Loads During Official Matches. AB - Castillo, D, Castagna, C, Camara, J, Iturricastillo, A, and Yanci, J. Influence of team's rank on soccer referees' external and internal match loads during official matches. J Strength Cond Res 32(6): 1715-1722, 2018-The aim was to examine the external and the internal match loads (ML) of field referees (FRs) attending teams of different ranking during championship matches. Twenty FR who officiated in 30 official soccer matches (30 observations) participated in our study. The criteria for allocating the soccer referees' ML results were based on the teams' final league positions as follows: matches performed by Top 10 teams (TOP10), matches performed by bottom 10 teams (BOT10), and matches played among TOP10 and BOT10 teams (MIXED). External (match activities, accelerations [Acc], and decelerations [Dec]) and internal MLs (Edwards' heart rate [HR]-derived training impulse [TRIMPEDW], HRmean expressed as a percentage of HRpeak [%HRpeak], and differentiated rating of perceived exertion [dRPE]) were recorded. The main results showed that FR, who officiated TOP10 matches, covered more distance at a low walking speed (<3.6 km.h) and performed a higher percentage of high-intensity accelerations and decelerations than those FR who officiated lower ranked teams' matches. Moreover, FR who officiated MIXED matches registered lower values of TRIMPEDW MLs and %HRpeak and declared higher respiratory (sRPEres ML) and muscular (sRPEmus ML) perceived MLs during the second half. Considering those FR who officiate matches between teams of a higher competitive level will need to produce higher match responses, especially regarding the percentage of distance covered at high intensity, accelerations, and decelerations; physical trainers of soccer referees at a high competitive level should implement these high-intensity short-term actions in specific training regimes. PMID- 29786627 TI - Association of Physical and Technical Activities With Partial Match Status in a Soccer Professional Team. AB - Moalla, W, Fessi, MS, Makni, E, Dellal, A, Filetti, C, Di Salvo, V, and Chamari, K. Association of physical and technical activities with partial match status in a soccer professional team. J Strength Cond Res 32(6): 1708-1714, 2018-The purpose of this study was to examine the association between physical and technical activities and partial match status (winning, drawing, or losing) in a professional soccer team over 2 seasons. Physical and technical activities of 52 official matches were collected and analyzed at each 15-minute interval, for each half (45 minutes), and full match (90 minutes) using a multiple-camera computerized tracking system. The results indicated that according to full match outcome: winning status was characterized by players covering more total distance (p <= 0.05) and low-intensity running (<14.4 km.h) (p <= 0.05), whereas, losing status induced more sprinting (>=25.2 km.h) (p < 0.01) and high-intensity running (>=19.8 km.h) (p <= 0.05). However, according to partial match status (i.e., 15 minutes and half time), players covered more distance for all running intensities while winning (p < 0.01). Technical match performance scores were not influenced by match status. In conclusion, the present study showed that the physical activities including high-intensity running and total distance covered were related to the match status, whereas technical activities were not. The overall outcome shows that higher physical activity was associated with winning partial match periods. This approach highlights the importance of physical fitness in soccer and may help coaches to better modulate players' roles and team tactical organization throughout the match. PMID- 29786629 TI - Anthropometric Parameters, Age, and Agility as Performance Predictors in Elite Female Basketball Players. AB - Garcia-Gil, M, Torres-Unda, J, Esain, I, Dunabeitia, I, Gil, SM, Gil, J, and Irazusta, J. Anthropometric parameters, age, and agility as performance predictors in elite female basketball players. J Strength Cond Res 32(6): 1723 1730, 2018-In addition to technical, tactical, and psychological skills, performance in playing basketball depends on anthropometry and physical fitness. However, limited information is available regarding such features in women. We hypothesized that anthropometry and physical fitness are associated with female basketball performance, and consequently, performance could be predicted using the results of certain anthropometric measures and fitness tests. Body parameters (age, height, body mass, skinfold thicknesses, limb perimeters, and lengths) were measured. Physical fitness capacities (jumping, agility with and without the ball, and speed) were measured by specific tests. In addition, game performance was assessed using technical statistics (rebounds, assists, and points) and the performance index rating (PIR). Teams ranked better in the regular season had smaller mean fat skinfold thickness and spent less time in the agility tests (T Drill). Correlation analyses indicated that players with better PIR were older, taller, and had a longer arm span and greater contracted arm perimeter (CAP). Furthermore, those players had better results in the T-Drill test. Multiple regression analysis indicated that combined age, height, CAP, fat skinfold thickness, and time in T-Drill test yielded a strong predictor of PIR per time played. In conclusion, the results of the present study indicate that some anthropometric and physical fitness characteristics of female elite basketball teams and players are highly associated with performance-related parameters. In addition, a regression model has been developed to predict the performance of female basketball players. PMID- 29786630 TI - Effect of Cadence on Time Trial Performance in Recreational Female Cyclists. AB - Graham, PL, Zoeller, RF, Jacobs, PL, and Whitehurst, MA. Effect of cadence on time trial performance in recreational female cyclists. J Strength Cond Res 32(6): 1739-1744, 2018-The impact of pedaling cadence on cycling performance remains unresolved especially in female cyclists. The purpose of this study was to determine the effect of cadence on time trial (TT) performance in recreational female cyclists. Ten recreational female cyclists volunteered to participate in this study. Subjects performed 3 exercise sessions: 1 to assess peak oxygen uptake (V[Combining Dot Above]O2peak) and 2 TTs. Cadence was randomly ordered and fixed for each TT (60 or 100 rpm), whereas power output (PO) was freely adjusted by the participant, as tolerated. Time trial time, heart rate (HR), blood lactate, PO, V[Combining Dot Above]O2, and ratings of perceived exertion were measured throughout the TTs. The major finding of this study was the significantly faster (p = 0.001) TT time during the 60-rpm condition (34:23 +/- 4:21) vs. the 100-rpm condition (37:34 +/- 5:53). Also the 60-rpm TT resulted in significant differences for HR (155.9 +/- 3.97 vs. 161.2 +/- 5.20 b.min, p = 0.04), gross efficiency, (21.1 +/- 0.37 vs. 17.7 +/- 0.85%, p < 0.001), and PO (147 +/- 7.06 vs. 129 +/- 10.62 W, p = 0.003). Thus, a slower cycling cadence was associated with greater mechanical efficiency and PO, resulting in significantly better performance in a TT. These results suggest that recreational female cyclists may benefit from adopting a low cadence during an 8-km TT. PMID- 29786631 TI - Comparison Between Elite and Subelite Swimmers on Dry Land and Tumble Turn Leg Extensor Force-Time Characteristics. AB - Jones, JV, Pyne, DB, Haff, GG, and Newton, RU. Comparison between elite and subelite swimmers on dry land and tumble turn leg extensor force-time characteristics. J Strength Cond Res 32(6): 1762-1769, 2018-Elite swimmers demonstrate faster swimming turn times that are potentially a result of having better strength-power characteristics than subelite swimmers. We quantified differences between dry-land and swimming turn force-time characteristics in elite swimmers and subelite swimmers. Subelite (11 males: 17.4 +/- 0.6 years; 10 females: 17.1 +/- 0.6 years) and elite swimmers (15 male: 23.2 +/- 2.3 years; 7 female: 21.6 +/- 2.5 years) were tested in a cross-sectional design. All swimmers performed a body weight and loaded (20 kg females, 30 kg males) squat jump (SJ) on a portable force platform. On the same day, all swimmers completed swimming turn analyses using a force platform fixed within the pool wall. The magnitude of difference between groups was estimated using a standardized mean difference (effect size statistic). Elite male and female swimmers had superior swimming turn and dry-land force-time characteristics to subelite swimmers in all tests. The standardized mean differences between groups ranged from small to very large. The largest differences were SJ peak velocity unloaded (3.07 +/- 1.0 m.s males, 3.49 +/- 2.29 m.s females; standardized mean difference +/- 90% confidence limits) and SJ peak power unloaded (2.59 +/- 0.79 w male, 2.80 +/- 1.64 w female) with elite male and female swimmers having a ~25-50% higher performance than the subelites in both characteristics. Elite swimmers exhibit superior strength and power characteristics for the swimming turn compared with younger and less experienced swimmers. A well-planned and executed strength and conditioning program is needed for emerging swimmers to develop these qualities, as they transition to senior levels. PMID- 29786632 TI - Influences of Playing Position and Quality of Opposition on Standardized Relative Distance Covered in Domestic Women's Field Hockey: Implications for Coaches. AB - Vinson, D, Gerrett, N, and James, DVB. Influences of playing position and quality of opposition on standardized relative distance covered in domestic women's field hockey: Implications for coaches. J Strength Cond Res 32(6): 1770-1777, 2018-The purpose of this study was to compare the standardized relative distance covered by the various playing positions (defenders, midfielders, and forwards) against different quality of opponents in domestic women's field hockey. Data were collected from 13 individuals competing for 1 team in the English Premier League across an 18-game season. Data were collected using portable global positioning system technology. Distance data were grouped into 6 speed zones relative to individual players' maximum sprint speeds and then standardized by dividing by the number of on-pitch minutes. Dependent variables included distance covered in the 6 speed zones, as well as the number of sprints and repeated sprint efforts (RSEs) completed in the highest speed zone. Participants covered a significantly greater total distance when competing against opponents from top 3 teams compared with middle 3 teams (111.78 +/- 2.65 m.min vs. 107.35 +/- 2.62 m.min, respectively). This was also true for distance covered in zone 4 (running) (29.47 +/- 1.69 m.min vs. 27.62 +/- 1.45 m.min, respectively) and zone 5 (fast running) (23.42 +/- 1.76 m.min vs. 21.52 +/- 1.79 m.min, respectively). Defenders (99.77 +/- 4.36 m.min) covered significantly less total meters per minute than midfielders (117.20 +/- 4.36 m.min) and completed significantly fewer RSEs per on pitch minute (0.21 +/- 0.03 and 0.33 +/- 0.03, respectively). Midfielders covered significantly less distance in zone 2 (walking) than forwards (19.38 +/- 1.64 m.min and 30.33 +/- 2.12 m.min, respectively). Conversely, midfielders were shown to cover significantly more distance in zone 3 (jogging) than forwards (32.84 +/- 1.10 m.min and 24.61 +/- 1.42 m.min, respectively). A standardized and relative assessment may be useful for coaches' and performance analysts' understanding of players' performance in different positions or against different quality opponents. PMID- 29786633 TI - The Effect of Nitrate Supplementation on Exercise Tolerance and Performance: A Systematic Review and Meta-Analysis. AB - Van De Walle, GP and Vukovich, MD. The effect of nitrate supplementation on exercise tolerance and performance: a systematic review and meta-analysis. J Strength Cond Res 32(6): 1796-1808, 2018-The purpose of this article was to systematically review the current literature and evaluate the overall efficacy of nitrate supplementation on exercise tolerance and performance by meta-analysis. Studies were eligible for inclusion if they met the following criteria: (a) were an experimental trial published in an English peer-reviewed journal; (b) compared the effects of inorganic nitrate consumption with a non-bioactive supplement control or placebo; (c) used a quantifiable measure of exercise performance; and (d) was carried out in apparently healthy participants without disease. A total of 29 studies were identified that investigated the effects of nitrate supplementation on exercise tolerance or performance in accordance with the criteria outlined. Analysis using time to exhaustion as the outcome variable revealed a significant effect of nitrate supplementation on exercise tolerance (ES = 0.28; 95% confidence interval [CI]: 0.08-0.47; p = 0.006) compared with placebo. Analysis using time to complete a specific distance as the outcome variable revealed no significant effect of nitrate supplementation on exercise performance (ES = -0.05; 95% CI: -0.28 to 0.17; p = 0.64) compared with placebo. Nitrate supplementation is likely to improve exercise tolerance and capacity that may improve exercise performance. More research is required to determine the optimal dose and duration of nitrate supplementation. It would also be important to consider the type of athlete performing the exercise and the duration, intensity, and mode of the exercise performed because these factors are likely to influence the efficacy of nitrate supplementation. PMID- 29786634 TI - Virophages and Their Interactions with Giant Viruses and Host Cells. AB - Virophages are small dsDNA viruses that were first isolated in association with some giant viruses (GVs), and then found in metagenomics samples. They encode about 20-34 proteins. Some virophages share protein similarity with Maverick/Polinton transposons or are considered as a provirophage, whereas about half of the protein's repertoire remain of unknown function. In this review, we aim to highlight the current understanding of the biology of virophages, as well as their interactions with giant viruses and host cells. Additionally, the virophage proteomes were analyzed to find the functional domains that distinguish each virophage. This bioinformatics analysis will benefit further experimental investigations to understand the protein-protein interactions between virophages, giant viruses, and host cells. PMID- 29786635 TI - Mechanical Behavior Optimization of Chitosan Extracted from Shrimp Shells as a Sustainable Material for Shopping Bags. AB - The use of biodegradable materials for shopping bag production, and other products made from plastics, has recently been an object of intense research-with the aim of reducing the environmental burdens given by conventional materials. Chitosan is a potential material because of its biocompatibility, degradability, and non-toxicity. It is a semi-natural biopolymeric material produced by the deacetylation of chitin, which is the second most abundant natural biopolymer (after cellulose). Chitin is found in the exoskeleton of insects, marine crustaceans, and the cell walls of certain fungi and algae. The raw materials most abundantly available are the shells of crab, shrimp, and prawn. Hence, in this study chitosan was selected as one of the main components of biodegradable materials used for shopping bag production. Firstly, chitin was extracted from shrimp shell waste and then converted to chitosan. The chitosan was next ground to a powder. Although, currently, polyethylene bags are prepared by blown extrusion, in this preliminary research the chitosan powder was dissolved in a solvent and the films were cast. Composite films with several fillers were used as a reinforcement at different dosages to optimize mechanical properties, which have been assessed using tensile tests. These results were compared with those of conventional polyethylene bags used in Egypt. Overall, the chitosan films were found to have a lower ductility but appeared to be strong enough to fulfill shopping bag functions. The addition of fillers, such as chitin whiskers and rice straw, enhanced the mechanical properties of chitosan films, while the addition of chitin worsened overall mechanical behavior. PMID- 29786636 TI - Standard Reference Materials for Cement Paste: Part II-Determination of Mixing Ratios. AB - A variety of special concrete structures have been designed for domestic and overseas construction markets that require highly advanced construction technology. Therefore, it is necessary to secure quantitative construction technology and develop a standard reference material (hereinafter: SRM) with consistent flow performance and quality in order to evaluate the quantitative performance of flowability. On the other hand, the flowability of concrete is influenced greatly by the flowability of the cement paste. In addition, considering the design strength and workability, the mix design was carried out at various mixing ratios, according to the purpose of the site. Therefore, based on the derived components of standard reference materials for cement paste, this paper proposes a mixing ratio for standard reference materials that can uniformly simulate the flow characteristics of cement paste, according to the water-cement ratio (W/C). The results show that yield stress was determined by the ratio of water and glycerol while plastic viscosity was controlled by the limestone content. Finally, the mixing ratio of standard reference materials that can simulate the rheological properties of cement paste by W/C was suggested. PMID- 29786637 TI - Dog Theft: A Case for Tougher Sentencing Legislation. AB - Dogs, and other companion animals, are currently classed as "property" in theft sentencing legislation for England and Wales. This means that offenders who steal dogs are given similar sentences to those that steal inanimate objects. This review presents the argument that the penalty for dog theft should be more severe than for the theft of non-living property. Evidence of the unique bond between dogs and humans, and discussion of the implications of labelling a living being as mere "property" are used to support this argument. The review concludes that the Sentencing Council's guidelines should be amended so that offences involving the theft of a companion animal are deemed to be a Category 2 offence or above. The review further proposes that "theft of a companion animal" should be listed in the Sentencing Council's guidelines as an aggravating factor. PMID- 29786638 TI - Impact of Appointment-Based Medication Synchronization on Proportion of Days Covered for Chronic Medications. AB - Appointment-based medication synchronization (ABMS) programs have been associated with increased adherence and persistence to chronic medications. Adherence to statin therapy, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and non-insulin antidiabetic medications (NIDM) are used to determine a health plan's Centers for Medicare and Medicaid Services (CMS) Star Rating under a pay-for-performance model. The objective of this study was to evaluate the impact of implementing an ABMS program on overall pharmacy adherence measures for statins, ACEI/ARBs, and NIDM, as presented through the Electronic Quality Improvement Platform for Plans and Pharmacies (EQuIPP(c)) platform. This retrospective, pre-post ABMS program study evaluated EQuIPP(c) generated adherence performance measures, represented as proportion of days covered (PDC), 6-months before and 6- and 12-months after the ABMS service for statin therapy, ACEIs/ARBs, and NIDM. All adherence measures showed statistically significant improvement in PDC percentage post ABMS implementation, except for NIDM percentage in 6-months post-ABMS service. This study shows that a comprehensive medication synchronization program can enhance adherence measures that are important to health plans to increase CMS Star Rating under a pay-for performance model. PMID- 29786639 TI - Chemogenetic Enhancement of Axon Regeneration Following Peripheral Nerve Injury in the SLICK-A Mouse. AB - The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i.p.), or were untreated controls. Two weeks after injury, the lengths of YFP+ axon profiles were measured in nerves harvested from euthanized animals. Compared to untreated controls, regenerating axon lengths were not significantly longer in mice treated only once with CNO, but they were more than three times longer in mice receiving CNO repeatedly. Based on results of retrograde labeling experiments, axons of more sensory and motor neurons had regenerated successfully in mice receiving multiple CNO treatments than animals receiving only one treatment or no treatments. The increase in numbers of labeled sensory, but not motor neurons could be accounted for by increases in the proportion of retrogradely labeled neurons also expressing the DREADD. Chemogenetic increases in neuronal excitability represent a potent and innovative treatment to promote peripheral nerve regeneration. PMID- 29786641 TI - Photothermal Effectiveness of Magnetite Nanoparticles: Dependence upon Particle Size Probed by Experiment and Simulation. AB - The photothermal effect of nanoparticles has proven efficient for driving diverse physical and chemical processes; however, we know of no study addressing the dependence of efficacy on nanoparticle size. Herein, we report on the photothermal effect of three different sizes (5.5 nm, 10 nm and 15 nm in diameter) of magnetite nanoparticles (MNP) driving the decomposition of poly(propylene carbonate) (PPC). We find that the chemical effectiveness of the photothermal effect is positively correlated with particle volume. Numerical simulations of the photothermal heating of PPC supports this observation, showing that larger particles are able to heat larger volumes of PPC for longer periods of time. The increased heating duration is likely due to increased heat capacity, which is why the volume of the particle functions as a ready guide for the photothermal efficacy. PMID- 29786643 TI - Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure. AB - Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Delta8-THC lowers intraocular pressure (IOP). Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Delta8-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors. However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy. We have recently shown that blocking monoacylglycerol lipase (MAGL), an enzyme that breaks the endocannabinoid 2-arachidonoyl glycerol (2-AG), substantially lowers IOP. Another strategy is to develop cannabinoid CB1 receptor agonists that are optimized for topical application to the eye. Recently we have reported on a controlled-deactivation approach where the "soft" drug concept of enzymatic deactivation was combined with a "depot effect" that is commonly observed with Delta8-THC and other lipophilic cannabinoids. This approach allowed us to develop novel cannabinoids with a predictable duration of action and is particularly attractive for the design of CB1 activators for ophthalmic use with limited or no psychoactive effects. We have tested a novel class of compounds using a combination of electrophysiology in autaptic hippocampal neurons, a well characterized model of endogenous cannabinoid signaling, and measurements of IOP in a mouse model. We now report that AM7410 is a reasonably potent and efficacious agonist at CB1 in neurons and that it substantially (30%) lowers IOP for as long as 5 h after a single topical treatment. This effect is absent in CB1 knockout mice. Our results indicate that the direct targeting of CB1 receptors with controlled-deactivation ligands is a viable approach to lower IOP in a murine model and merits further study in other model systems. PMID- 29786640 TI - Vitamin D in Vascular Calcification: A Double-Edged Sword? AB - Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification. Therefore, more complex underlying processes involving physiochemical changes to mineral balance, vascular remodelling and perturbed hormonal responses such as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) are likely to contribute to VC. In particular, VC resulting from modifications to calcium, phosphate and vitamin D homeostasis has been recently elucidated. Notably, deregulation of vitamin D metabolism, dietary calcium intake and renal mineral handling are associated with imbalances in systemic calcium and phosphate levels and endothelial cell dysfunction, which can modulate both bone and soft tissue calcification. This review addresses the current understanding of VC pathophysiology, with a focus on the pathogenic role of vitamin D that has provided new insights into the mechanisms of VC. PMID- 29786642 TI - Determining the Radiation Enhancement Effects of Gold Nanoparticles in Cells in a Combined Treatment with Cisplatin and Radiation at Therapeutic Megavoltage Energies. AB - Combined use of chemotherapy and radiation therapy is commonly used in cancer treatment, but the toxic effects on normal tissue are a major limitation. This study assesses the potential to improve radiation therapy when combining gold nanoparticle (GNP) mediated radiation sensitization with chemoradiation compared to chemoradiation alone. Incorporation of GNPs with 2 Gy, 6 MV (megavoltage) radiation resulted in a 19 +/- 6% decrease in survival of MDA-MB-231 cells. Monte Carlo simulations were performed to assess dosimetric differences in the presence of GNPs in radiation. The results show that physics dosimetry represents a small fraction of the observed effect. The survival fraction of the cells exposed to GNPs, cisplatin, and radiation was 0.16 +/- 0.007, while cells treated with cisplatin and radiation only was 0.23 +/- 0.011. The presence of GNPs resulted in a 30 +/- 6% decrease in the survival, having an additive effect. The concentration of the GNPs and free drug used for this study was 0.3 and 435 nM, respectively. These concentrations are relatively lower and achievable in an in vivo setting. Hence, the results of our study would accelerate the incorporation of GNP-mediated chemoradiation into current cancer therapeutic protocols in the near future. PMID- 29786645 TI - Skeletal Muscle MicroRNAs as Key Players in the Pathogenesis of Amyotrophic Lateral Sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions. In this review, we summarize how the expression of some microRNAs is dysregulated in the skeletal muscle of ALS mouse models and patients. Shedding light on the mechanisms underlying microRNAs dysregulation in the skeletal muscle could clarify some of the processes involved in the pathogenesis of ALS and especially identify new promising therapeutic targets in patients. PMID- 29786644 TI - Impact of Bone Fracture on Ischemic Stroke Recovery. AB - Stroke is one of the most devastating complications of bone fracture, occurring in up to 4% of patients after surgical repair for hip fracture. Bone fracture and ischemic stroke have many common risk factors. The impact of bone fracture on stroke recovery has not drawn much attention in the research field. Bone fracture could occur in stroke patients at different times during the recovery phase, which steepens the trajectory of cognitive decline, greatly affects the quality of life, and causes a heavy burden on healthcare resources. In this paper, we reviewed the growing information on the pathophysiological mechanisms by which bone fracture may affect ischemic stroke recovery process. PMID- 29786647 TI - Health Disparities Score Composite of Youth and Parent Dyads from an Obesity Prevention Intervention: iCook 4-H. AB - iCook 4-H is a lifestyle intervention to improve diet, physical activity and mealtime behavior. Control and treatment dyads (adult primary meal preparer and a 9-10-year-old youth) completed surveys at baseline and 4, 12, and 24 months. A Health Disparity (HD) score composite was developed utilizing a series of 12 questions (maximum score = 12 with a higher score indicating a more severe health disparity). Questions came from the USDA short form U.S. Household Food Security Survey (5), participation in food assistance programs (1), food behavior (2), level of adult education completed (1), marital status (1), and race (1 adult and 1 child). There were 228 dyads (control n = 77; treatment n = 151) enrolled in the iCook 4-H study. Baseline HD scores were 3.00 +/- 2.56 among control dyads and 2.97 +/- 2.91 among treatment dyads, p = 0.6632. There was a significant decline in the HD score of the treatment group from baseline to 12 months (p = 0.0047) and baseline to 24 months (p = 0.0354). A treatment by 12-month time interaction was found (baseline mean 2.97 +/- 2.91 vs. 12-month mean 1.78 +/- 2.31; p = 0.0406). This study shows that behavioral change interventions for youth and adults can help improve factors that impact health equity; although, further research is needed to validate this HD score as a measure of health disparities across time. PMID- 29786646 TI - Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression. AB - Obesity is a complex disease associated with environmental and genetic factors. 3 Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways. In liver, we observed an increased gene and protein expression of Sirt6 (a master gene regulator of glucose) and Gck (glucose kinase) and a decreased expression of Sirt4 (a negative regulator of fatty acids oxidation (FAO)), whereas in white adipose tissue only Sirt6 was increased. Metabolomics analysis supported physiological changes at both doses with most increases in FAO, glycolysis indicators and the mitochondrial substrate, at the highest dose of T1AM. Together our results suggest that T1AM acts through sirtuin-mediated pathways to metabolically reprogram fatty acid and glucose metabolism possibly through small molecules signaling. Our novel mechanistic findings indicate that T1AM has a great potential as a drug for the treatment of obesity and possibly diabetes. PMID- 29786648 TI - Utilizing Optimized Tools to Investigate PTM Crosstalk: Identifying Potential PTM Crosstalk of Acetylated Mitochondrial Proteins. AB - Post-translational modification (PTM) crosstalk is recognized as a major cell regulatory mechanism, and studies of several proteins have validated the premise that PTMs work in concert. Previous work by our group investigated the potential PTM crosstalk on proteins in the EGFR-Ras-c-Fos axis by utilizing a comprehensive set of PTM reagents termed Signal-Seeker toolkits. In this study, these tools were used to investigate the potential PTM crosstalk that occurs in acetylated mitochondrial proteins in response to a mitochondrial stress-inducing agent hydrogen peroxide (H2O2). Mitochondrial protein acetylation has been shown to participate in PTM crosstalk as exemplified by the regulation of the pyruvate dehydrogenase complex via kinase, phosphatase, acetyltransferase, and deacetylase activities. Changes in the acetylated state of mitochondrial proteins were investigated, in response to H2O2, using a novel anti acetyl lysine (Ac-K) antibody. Signal-Seeker PTM detection tools were used to validate the acetylation state of ten mitochondrial targets, as well as their endogenous acetylation state in response to H2O2. Importantly, the endogenous acetylation, ubiquitination, SUMOylation 2/3, and tyrosine phosphorylation state of four target mitochondrial proteins were also investigated with the toolkit. Each of the four proteins had unique PTM profiles, but diverging acetylation and ubiquitin or SUMO 2/3 signals appeared to be a common theme. This proof-of-concept study identifies the Signal Seeker toolkits as a useful tool to investigate potential PTM crosstalk. PMID- 29786650 TI - A Review of Tunable Wavelength Selectivity of Metamaterials in Near-Field and Far Field Radiative Thermal Transport. AB - Radiative thermal transport of metamaterials has begun to play a significant role in thermal science and has great engineering applications. When the key features of structures become comparable to the thermal wavelength at a particular temperature, a narrowband or wideband of wavelengths can be created or shifted in both the emission and reflection spectrum of nanoscale metamaterials. Due to the near-field effect, the phenomena of radiative wavelength selectivity become significant. These effects show strong promise for applications in thermophotovoltaic energy harvesting, nanoscale biosensing, and increased energy efficiency through radiative cooling in the near future. This review paper summarizes the recent progress and outlook of both near-field and far-field radiative heat transfer, different design structures of metamaterials, applications of unique thermal and optical properties, and focuses especially on exploration of the tunable radiative wavelength selectivity of nano metamaterials. PMID- 29786652 TI - Consumer Perception of the Quality of Lamb and Lamb Confit. AB - The patterns of food consumption in general and those of meat, in particular, are constantly changing. These changes are due not only to socioeconomic and cultural trends that affect the whole society but also to the specific lifestyles of consumer groups. Due to the importance of consumer lifestyle, the objectives of this study were (i) to identify the profiles of lamb meat consumers according to their orientation toward convenience, as defined by their eating and cooking habits; (ii) to characterize these profiles according to their socioeconomic characteristics and their preferences regarding the intrinsic and extrinsic quality signals of lamb meat; and (iii) to analyze the willingness to pay for lamb confit. In this study, four types of consumers have been differentiated according to their lifestyles related to lamb consumption. These groups, due to their characteristics, could be called "Gourmet", "Disinterested", "Conservative", and "Basic". The Gourmet group has characteristics that make it especially interesting to market a product such as lamb confit. However, this group is unaware of this product. Therefore, a possible strategy to expand the commercialization of light lamb and the confit product would be guided marketing to this niche market. PMID- 29786651 TI - Clinical Efficacy Associated with Enhanced Antioxidant Enzyme Activities of Silver Nanoparticles Biosynthesized Using Moringa oleifera Leaf Extract, Against Cutaneous Leishmaniasis in a Murine Model of Leishmania major. AB - Leishmaniasis is one of the most significant vector-borne syndromes of individuals. This parasitic infection can be affected by many species of Leishmania, most of which are zoonotic. Natural products have made and are continuing to make important contributions to the search for new antileishmanial agents. The use of plants in the production assembly of silver nanoparticles has drawn attention because of its rapid, eco-friendly, non-pathogenic, economical protocol and provides a single step technique for the biosynthetic process. Hence, we aimed to biosynthesize silver nanoparticles (Ag-NPs) using Moringa oleifera leaf extract and investigated the antileishmanial activity of these nanoparticles in a murine model of Leishmania major infection. A total of 50 mice were used and divided into five groups-healthy control, infected, infected mice treated with pentostam, infected mice treated with Ag-NPs and infected mice pretreated with Ag-NPs. In the present study, the leaf extract of the plant species Moringa oleifera was found to be a good source for the synthesis of silver nanoparticles, their formation being confirmed by color change and stability in solution. In the present murine model of Leishmania major infection, we found that oral treatment with silver nanoparticles biosynthesized using Moringa oleifera extract resulted in a significant reduction in the average size of leishmaniasis cutaneous lesions compared with untreated mice. Furthermore, the clinical efficacy of Moringa oleifera extract was associated with enhanced antioxidant enzyme activities. In conclusion, treatment with silver nanoparticles biosynthesized using Moringa oleifera extract has higher and faster clinical efficacy than standard pentavalent antimonial treatment, probably by boosting the endogenous antioxidant activity. PMID- 29786649 TI - Kudzu Leaf Extract Suppresses the Production of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, Tumor Necrosis Factor-Alpha, and Interleukin-6 via Inhibition of JNK, TBK1 and STAT1 in Inflammatory Macrophages. AB - Kudzu (Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) is a perennial leguminous vine, and its root and flower have been used for herbal medicine in Asia for a long time. Most dietary flavonoids are reported to be concentrated in its root, not in its aerial parts including leaves. In this study, we investigated whether kudzu leaf and its major constituent, robinin (kaempferol-3 O-robinoside-7-O-rhanmoside) possessed anti-inflammatory activity. To test this hypothesis, we used peritoneal macrophages isolated from BALB/c mice and stimulated the cells with lipopolysaccharide (LPS) or LPS plus interferon (IFN) gamma. Compared with kudzu root extract, its leaf extract was more potent in inhibiting the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-6. Kudzu leaf extract decreased LPS-induced activation of c-Jun N-terminal kinase (JNK) and TANK-binding kinase 1(TBK1) with no effects on nuclear factor-kappaB and activator protein 1 transcriptional activity. Also, kudzu leaf extract inhibited LPS/IFN-gamma-induced signal transducer and activator of transcription 1 (STAT1) activation partly via an altered level of STAT1 expression. Robinin, being present in 0.46% of dry weight of leaf extract, but almost undetected in the root, decreased iNOS protein involving modulation of JNK and STAT1 activation. However, robinin showed no impact on other inflammatory markers. Our data provide evidence that kudzu leaf is an excellent food source of as yet unknown anti inflammatory constituents. PMID- 29786654 TI - A Comparative Study of Oral Health Status between International and Japanese University Student Patients in Japan. AB - Background: The number of international students enrolled in universities in Japan is increasing. To provide better oral care services for international students, we have to understand their oral environment and dental health behaviors. However, few studies have investigated the oral health status of international university students. The object of the present study was to clarify the current oral status of international university students. Methods: The subjects were students who visited the dental department at the University of Tokyo's Health Services Center between April 2012 and March 2013. Our medical records were reviewed with regard to the following items: attributes (nationality, gender, and age); chief complaint (reason for visit); history of dental treatment; mean number of decayed (D), missing (M) or filled (F) teeth as a single (DMFT) index; degree of calculus deposition; gingival condition; and oral hygiene status. Results: The records of 554 university students (138 international and 416 non-international students) were analyzed; 88.4% of the 138 international students were from Asian countries (n = 122), of which 47.1% were from China and 10.9% from Korea, followed by North America (5.8%), Europe (4.3%), and Africa (1.5%). Although no significant differences were found regarding the history of dental treatment between international and non-international students (49.3% and 48.8%, respectively), international students had a significantly higher dental caries morbidity rate (60.1%) than non-international students (49.0%). The international students showed a significantly higher DMFT value compared with the non-international students: 5.0 and 4.0 per individual, respectively. Severe calculus deposition was observed in international students compared with non-international students (51.9% and 31.7%, respectively). Conclusions: The international university students had poorer oral health status than the non-international students, even though the result might include many uncertainties and possible biases. PMID- 29786653 TI - Role for Cystathionine gamma Lyase (CSE) in an Ethanol (E)-Induced Lesion in Fetal Brain GSH Homeostasis. AB - Earlier, we reported that gestational ethanol (E) can dysregulate neuron glutathione (GSH) homeostasis partially via impairing the EAAC1-mediated inward transport of Cysteine (Cys) and this can affect fetal brain development. In this study, we investigated if there is a role for the transulfuration pathway (TSP), a critical bio-synthetic point to supply Cys in E-induced dysregulation of GSH homeostasis. These studies utilized an in utero E binge model where the pregnant Sprague-Dawley (SD) rat dams received five doses of E at 3.5 g/kg by gastric intubation beginning embryonic day (ED) 17 until ED19 separated by 12 h. The postnatal day 7 (PN7) alcohol model employed an oral dosing of 4 g/kg body weight split into 2 feedings at 2 h interval and an iso-caloric and iso-volumic equivalent maltose-dextrin milk solution served as controls. The in vitro model consisted of cerebral cortical neuron cultures from embryonic day (ED) 16-17 fetus from SD rats and differentiated neurons from ED18 rat cerebral cortical neuroblasts. E concentrations were 4 mg/mL. E induced an accumulation of cystathionine in primary cortical neurons (PCNs), 2nd trimester equivalent in utero binge, and 3rd trimester equivalent PN7 model suggesting that breakdown of cystathionine, a required process for Cys supply is impaired. This was associated with a significant reduction in cystathionine gamma-lyase (CSE) protein expression in PCN (p < 0.05) and in fetal cerebral cortex in utero (53%, p < 0.05) without a change in the expression of cystathionine beta-synthase (CBS). Concomitantly, E decreased Cse mRNA expression in PCNs (by 32% within 6 h of exposure, p < 0.05) and in fetal brain (33%, p < 0.05). In parallel, knock down of CSE in differentiated rat cortical neuroblasts exaggerated the E-induced ROS, GSH loss with a pronounced caspase-3 activation and cell death. These studies illustrate the importance of TSP in CSE-related maintenance of GSH and the downstream events via Cys synthesis in neurons and fetal brain. PMID- 29786655 TI - Bioactive Pyridone Alkaloids from a Deep-Sea-Derived Fungus Arthrinium sp. UJNMF0008. AB - Eight new 4-hydroxy-2-pyridone alkaloids arthpyrones D-K (1-8), along with two known analogues apiosporamide (9) and arthpyrone B (10), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. The structures of the isolated compounds were elucidated on the basis of spectroscopic methods with that of 1 being established by chemical transformation and X-ray diffraction analysis. Compounds 1 and 2 bore an ester functionality linking the pyridone and decalin moieties first reported in this class of metabolites, while 3 and 4 incorporated a rare natural hexa- or tetrahydrobenzofuro[3,2-c]pyridin-3(2H)-one motif. Compounds 3-6 and 9 exhibited moderate to significant antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus with IC50 values ranging from 1.66-42.8 MUM, while 9 displayed cytotoxicity against two human osteosarcoma cell lines (U2OS and MG63) with IC50 values of 19.3 and 11.7 MUM, respectively. PMID- 29786657 TI - Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin 24-Induced Apoptosis through Inhibition of Translation. AB - Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs). These mRNAs encode proteins, which function in cell survival and proliferation. Consistently, overexpression of eIF4A conferred cancer cells with resistance to IL-24-induced cell death. It has been established that inhibition of eIF4A triggers mitochondrial-mediated apoptosis. We showed that IL-24 induces eIF4A dependent mitochondrial depolarization. We also showed that IL-24 induces Sigma 1 Receptor-dependent eIF4A down-regulation and mitochondrial depolarization. Thus, the progress of apoptosis triggered by IL-24 is characterized by a complex program of changes in regulation of several initiation factors, including the eIF4A. PMID- 29786656 TI - Temperature Effects on Force and Actin-Myosin Interaction in Muscle: A Look Back on Some Experimental Findings. AB - Observations made in temperature studies on mammalian muscle during force development, shortening, and lengthening, are re-examined. The isometric force in active muscle goes up substantially on warming from less than 10 degrees C to temperatures closer to physiological (>30 degrees C), and the sigmoidal temperature dependence of this force has a half-maximum at ~10 degrees C. During steady shortening, when force is decreased to a steady level, the sigmoidal curve is more pronounced and shifted to higher temperatures, whereas, in lengthening muscle, the curve is shifted to lower temperatures, and there is a less marked increase with temperature. Even with a small rapid temperature-jump (T-jump), force in active muscle rises in a definitive way. The rate of tension rise is slower with adenosine diphosphate (ADP) and faster with increased phosphate. Analysis showed that a T-jump enhances an early, pre-phosphate release step in the acto-myosin (crossbridge) ATPase cycle, thus inducing a force-rise. The sigmoidal dependence of steady force on temperature is due to this endothermic nature of crossbridge force generation. During shortening, the force-generating step and the ATPase cycle are accelerated, whereas during lengthening, they are inhibited. The endothermic force generation is seen in different muscle types (fast, slow, and cardiac). The underlying mechanism may involve a structural change in attached myosin heads and/or their attachments on heat absorption. PMID- 29786658 TI - Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence. AB - Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions. To address this aim, a search of the literature was conducted using Pubmed, Google Scholar, and the Cochrane Database. In total, 239 unique articles were screened, and the 22 preclinical studies that met the a priori inclusion/exclusion criteria were summarized, including the study aims, sample (size, groups, species, strain, sex, age/weight), TBI model, therapeutic details (preparation, dose, route, duration), key findings, and conclusions. The evidence from these 22 studies was analyzed to draw comparisons across studies, identify remaining gaps, and suggest future directions. Taken together, the published evidence suggests that MEL has neuroprotective properties via a number of mechanisms with few toxic effects reported. Notably, available evidence is largely based on data from adult male rats and, to a lesser extent, mice. Few studies collected data beyond a few days of the initial injury, necessitating additional longer-term studies. Other future directions include diversification of samples to include female animals, pediatric and geriatric animals, and transgenic strains. PMID- 29786659 TI - Deep Learning to Predict Falls in Older Adults Based on Daily-Life Trunk Accelerometry. AB - Early detection of high fall risk is an essential component of fall prevention in older adults. Wearable sensors can provide valuable insight into daily-life activities; biomechanical features extracted from such inertial data have been shown to be of added value for the assessment of fall risk. Body-worn sensors such as accelerometers can provide valuable insight into fall risk. Currently, biomechanical features derived from accelerometer data are used for the assessment of fall risk. Here, we studied whether deep learning methods from machine learning are suited to automatically derive features from raw accelerometer data that assess fall risk. We used an existing dataset of 296 older adults. We compared the performance of three deep learning model architectures (convolutional neural network (CNN), long short-term memory (LSTM) and a combination of these two (ConvLSTM)) to each other and to a baseline model with biomechanical features on the same dataset. The results show that the deep learning models in a single-task learning mode are strong in recognition of identity of the subject, but that these models only slightly outperform the baseline method on fall risk assessment. When using multi-task learning, with gender and age as auxiliary tasks, deep learning models perform better. We also found that preprocessing of the data resulted in the best performance (AUC = 0.75). We conclude that deep learning models, and in particular multi-task learning, effectively assess fall risk on the basis of wearable sensor data. PMID- 29786661 TI - Suspended Carbon Nanotubes for Humidity Sensing. AB - A room temperature microfabrication technique using SU8, an epoxy-based highly functional photoresist as a sacrificial layer, is developed to obtain suspended aligned carbon nanotube beams. The humidity-sensing characteristics of aligned suspended single-walled carbon nanotube films are studied. A comparative study between suspended and non-suspended architectures is done by recording the resistance change in the nanotubes under humidity. For the tests, the humidity was varied from 15% to 98% RH. A comparative study between suspended and non suspended devices shows that the response and recovery times of the suspended devices was found to be almost 3 times shorter than the non-suspended devices. The suspended devices also showed minimal hysteresis even after 10 humidity cycles, and also exhibit enhanced sensitivity. Repeatability tests were performed by subjecting the sensors to continuous humidification cycles. All tests reported here have been performed using pristine non-functionalized nanotubes. PMID- 29786662 TI - Study on the Discrimination between Citri Reticulatae Pericarpium Varieties Based on HS-SPME-GC-MS Combined with Multivariate Statistical Analyses. AB - Citri reticulatae pericarpium (CRP), the dried pericarps of Citrus reticulata Blanco and its cultivars, has been widely used in drugs and foods in China for centuries. In this study, an accurate and feasible analytical method based on HS SPME-GC-MS coupled with multivariate statistical analyses was developed to comprehensively compare volatile compounds of pericarps derived from Citrus reticulata "Chachi" ("Guangchenpi" in Chinese, GCP) and other cultivars of Citrus reticulata Blanco ("Chenpi" in Chinese, CP). Principal component analysis, hierarchical cluster analysis, and orthogonal partial least-squares discrimination analysis were performed to extract meaningful attributes from volatile profiles based on GC-MS data. Results indicated that samples from GCP and CP could easily be differentiated, and seven potential chemical markers were screened for the quality control of CRP. This study illuminated the volatile profile in CRP, and provides a practical method for the authentication of CRP varieties. PMID- 29786663 TI - Modeling the Effect of Primary and Secondary Twinning on Texture Evolution during Severe Plastic Deformation of a Twinning-Induced Plasticity Steel. AB - Modeling the effect of deformation twinning and the ensuing twin-twin- and slip twin-induced hardening is a long-standing problem in computational mechanical metallurgy of materials that deform by both slip and twinning. In this work, we address this effect using the twin volume transfer method, which obviates the need of any cumbersome criterion for twin variant selection. Additionally, this method is capable of capturing, at the same time, secondary or double twinning, which is particularly important for modeling in large strain regimes. We validate our modeling methodology by simulating the behavior of an Fe-23Mn-1.5Al-0.3C twinning-induced plasticity (TWIP) steel under large strain conditions, experimentally achieved in this work through equal-channel angular pressing (ECAP) for up to two passes in a 90 degrees die following route BC at 300 degrees C. Each possible twin variant, whether nucleating inside the parent grain or inside a potential primary twin variant was predefined in the initial list of orientations as possible grain of the polycrystal with zero initial volume fraction. A novelty of our approach is to take into account the loss of coherency of the twins with their parent matrix under large strains, obstructing progressively their further growth. This effect has been captured by attenuating growth rates of twins as a function of their rotation away from their perfect twin orientation, dubbed here as "disorientation" with respect to the mother grain's lattice. The simulated textures and the hardening under tensile strain showed very good agreement with experimental characterization and mechanical testing results. Furthermore, upper-bound Taylor deformation was found to be operational for the TWIP steel deformation when all the above ingredients of twinning are captured, indicating that self-consistent schemes can be bypassed. PMID- 29786664 TI - ENABLE 2017, the First EUROPEAN PhD and Post-Doc Symposium. Session 3: In Vitro to In Vivo: Modeling Life in 3D. AB - The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European research institutes (Institute for Research in Biomedicine-IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences-RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research-NNF CPR, Denmark; European School of Molecular Medicine-SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim to promote biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled "Breaking Down Complexity: Innovative models and techniques in biomedicine", was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists. PMID- 29786660 TI - Molecular Targets of Active Anticancer Compounds Derived from Marine Sources. AB - Over the past decades, a number of novel compounds, which are produced in the marine environment, have been found to exhibit the anticancer effects. This review focuses on molecular targets of marine-derived anticancer candidates in clinical and preclinical studies. They are kinases, transcription factors, histone deacetylase, the ubiquitin-proteasome system, and so on. Specific emphasis of this review paper is to provide information on the optimization of new target compounds for future research and development of anticancer drugs, based on the identification of structures of these target molecules and parallel compounds. PMID- 29786665 TI - Automated Field-of-View, Illumination, and Recognition Algorithm Design of a Vision System for Pick-and-Place Considering Colour Information in Illumination and Images. AB - Machine vision is playing an increasingly important role in industrial applications, and the automated design of image recognition systems has been a subject of intense research. This study has proposed a system for automatically designing the field-of-view (FOV) of a camera, the illumination strength and the parameters in a recognition algorithm. We formulated the design problem as an optimisation problem and used an experiment based on a hierarchical algorithm to solve it. The evaluation experiments using translucent plastics objects showed that the use of the proposed system resulted in an effective solution with a wide FOV, recognition of all objects and 0.32 mm and 0.4 degrees maximal positional and angular errors when all the RGB (red, green and blue) for illumination and R channel image for recognition were used. Though all the RGB illumination and grey scale images also provided recognition of all the objects, only a narrow FOV was selected. Moreover, full recognition was not achieved by using only G illumination and a grey-scale image. The results showed that the proposed method can automatically design the FOV, illumination and parameters in the recognition algorithm and that tuning all the RGB illumination is desirable even when single channel or grey-scale images are used for recognition. PMID- 29786667 TI - Mass Transfer in Osmotic Dehydration of Kiwiberry: Experimental and Mathematical Modelling Studies. AB - The aim of this study was to analyze the impact of osmotic solutions and temperature on the osmotic dehydration (OD) of two cultivars of kiwiberry. OD was carried out in sucrose, xylitol and maltitol solutions at 30 degrees C and 50 degrees C, respectively. The process of osmotic dehydration was described by the means of water loss (WL), solid gain (SG), weight reduction (WR), and water content changes. Moreover, dehydration was described by mathematical models often used in the literature. The highest WL, WR and SG values were observed for samples treated by xylitol and maltitol at 50 degrees C. The statistical analysis of the mathematical modelling of the process showed that in most cases, the Peleg's equation exhibits better fitting for the experimental data. PMID- 29786666 TI - Dopamine Receptor Subtypes Differentially Regulate Autophagy. AB - Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that dopamine receptors D2 and D3 (D2-like family) are positive regulators of autophagy, while dopamine receptors D1 and D5 (D1-like family) are negative regulators. Furthermore, dopamine and ammonia, the two reported endogenous ligands of dopamine receptors, both can induce dopamine receptor internalization and degradation. In addition, we found that AKT (protein kinase B)-mTOR (mechanistic target of rapamycin) and AMPK (AMP-activated protein kinase) pathways are involved in DRD3 (dopamine receptor D3) regulated autophagy. Moreover, autophagy machinery perturbation inhibited DRD3 degradation and increased DRD3 oligomer. Therefore, our study investigated the functions and mechanisms of dopamine receptors in autophagy regulation, which not only provides insights into better understanding of some dopamine receptor-related neurodegeneration diseases, but also sheds light on their potential treatment in combination with autophagy or mTOR pathway modulations. PMID- 29786668 TI - SCF/c-KIT Signaling Increased Mucin2 Production by Maintaining Atoh1 Expression in Mucinous Colorectal Adenocarcinoma. AB - Mucinous colorectal adenocarcinoma (MCA) patients often a show high risk of malignant potential and a poorer survival rate. Given that the pathological feature and oncobiological characteristics of MCA are correlated with its abundant extracellular mucin2 (MUC2), we paid interest toward investigating the key factor that promotes MUC2 production exposure to highly-activated stem cell factor (SCF)/c-KIT signaling, which we believed to contribute to MCA formation. Long-term azoxymethane and dextran sodium sulfate treatment successfully induced MCA only in wild-type (WT) mice at week 37 and 43, while all c-kit loss-of function mutant mice (Wadsm/m) developed non-MCA. Significantly, MUC2 and its key transcriptional factor Atonal homologue 1 (Atoh1) were remarkably expressed in MCA mice compared with non-MCA mice. Atoh1 was significantly elevated in colorectal cancer (CRC) cells stimulated by exogenous SCF or overexpressing c-KIT in vitro, while decreased by the blockage of SCF/c-KIT signaling with Imatinib. Furthermore, the maintained Atoh1 protein level was due to the inactive glycogen synthase kinase 3beta (p-GSK3beta) by virtue of the activated SCF/c-KIT-Protein Kinase B (AKT) signaling. Similar results were obtained from the ONCOMINE database and CRC patients. In conclusion, we suggested that SCF/c-KIT signaling promoted MUC2 production and MCA tumorigenesis by maintaining Atoh1 expression. Therefore, targeting the related key molecules might be beneficial for treating MCA patients. PMID- 29786669 TI - Protein Tyrosine Phosphatase 1B Inhibition and Glucose Uptake Potentials of Mulberrofuran G, Albanol B, and Kuwanon G from Root Bark of Morus alba L. in Insulin-Resistant HepG2 Cells: An In Vitro and In Silico Study. AB - Type II diabetes mellitus (T2DM) is the most common form of diabetes and has become a major health problem across the world. The root bark of Morus alba L. is widely used in Traditional Chinese Medicine for treatment and management of diabetes. The aim of the present study was to evaluate the enzyme inhibitory potentials of three principle components, mulberrofuran G (1), albanol B (2), and kuwanon G (3) in M. alba root bark against diabetes, establish their enzyme kinetics, carry out a molecular docking simulation, and demonstrate the glucose uptake activity in insulin-resistant HepG2 cells. Compounds 1-3 showed potent mixed-type enzyme inhibition against protein tyrosine phosphatase 1B (PTP1B) and alpha-glucosidase. In particular, molecular docking simulations of 1-3 demonstrated negative binding energies in both enzymes. Moreover, 1-3 were non toxic up to 5 uM concentration in HepG2 cells and enhanced glucose uptake significantly and decreased PTP1B expression in a dose-dependent manner in insulin-resistant HepG2 cells. Our overall results depict 1-3 from M. alba root bark as dual inhibitors of PTP1B and alpha-glucosidase enzymes, as well as insulin sensitizers. These active constituents in M. alba may potentially be utilized as an effective treatment for T2DM. PMID- 29786670 TI - Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells. AB - Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required. Nuclear factor kappa B (NF-kappaB) transcription factors are associated with anti-apoptosis, carcinogenesis, and chemoresistance, and thus, constitute attractive targets for therapeutic intervention. In immunoblots, we show that ubiquitin specific protease 47 (USP47) promotes beta-transducin repeat-containing protein (betaTrCP) stability and phosphorylation of RelA. Furthermore, after knockdown of USP47 by RNA interference, we analyzed in gastric cancer cell lines metabolic activity/viability in an MTT assay, and apoptotic cell death by Annexin V staining and poly(ADP-Ribose) polymerase (PARP)-1, caspase 3, and caspase 8 cleavage, respectively. We found that USP47 contributes to cell viability and chemoresistance in NCI-N87 gastric carcinoma cells treated with etoposide and camptothecin. Inhibition of USP47 might be a suitable strategy to downregulate NF kappaB activity, and to overcome chemoresistance in gastric cancer. PMID- 29786672 TI - The Impacts of Spatiotemporal Landscape Changes on Water Quality in Shenzhen, China. AB - The urban landscape in China has changed rapidly over the past four decades, which has led to various environmental consequences, such as water quality degradation at the regional scale. To improve water restoration strategies and policies, this study assessed the relationship between water quality and landscape change in Shenzhen, China, using panel regression analysis. The results show that decreases in natural and semi-natural landscape compositions have had significant negative effects on water quality. Landscape composition and configuration changes accounted for 39-58% of the variation in regional water quality degradation. Additionally, landscape fragmentation indices, such as patch density (PD) and the number of patches (NP), are important indicators of the drivers of water quality degradation. PD accounted for 2.03-5.44% of the variability in water quality, while NP accounted for -1.63% to -4.98% of the variability. These results indicate that reducing landscape fragmentation and enhancing natural landscape composition at the watershed scale are vital to improving regional water quality. The study findings suggest that urban landscape optimization is a promising strategy for mitigating urban water quality degradation, and the results can be used in policy making for the sustainable development of the hydrological environment in rapidly urbanizing areas. PMID- 29786673 TI - Fabrication Flexible and Luminescent Nanofibrillated Cellulose Films with Modified SrAl2O4: Eu, Dy Phosphors via Nanoscale Silica and Aminosilane. AB - Flexible 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized nanofibrillated cellulose (ONFC) films with long afterglow luminescence containing modified SrAl2O4: Eu2+, Dy3+ (SAOED) phosphors were fabricated by a template method. Tetraethyl orthosilicate (TEOS) and (3-aminopropyl) trimethoxy silane (APTMS) were employed cooperatively to improve the water resistance and compatibility of the SAOED particles in the ONFC suspension. The structure and morphology after modification evidenced the formation of a superior SiO2 layer and coarse amino-compounds on the surface of the phosphors. Homogeneous dispersions containing ONFC and the modified phosphors were prepared and the interface of composite films containing the amino-modified particles showed a more closely packed structure and had less voids at the interface between the cellulose and luminescent particles than that of silica-modified phosphors. The emission spectra for luminescent films showed a slight blue shift (3.2 nm) at around 512 nm. Such flexible films with good luminescence, thermal resistance, and mechanical properties can find applications in fields like luminous flexible equipment, night indication, and portable logo or labels. PMID- 29786671 TI - Mechanisms of Action and Cell Death Associated with Clostridium perfringens Toxins. AB - Clostridium perfringens uses its large arsenal of protein toxins to produce histotoxic, neurologic and intestinal infections in humans and animals. The major toxins involved in diseases are alpha (CPA), beta (CPB), epsilon (ETX), iota (ITX), enterotoxin (CPE), and necrotic B-like (NetB) toxins. CPA is the main virulence factor involved in gas gangrene in humans, whereas its role in animal diseases is limited and controversial. CPB is responsible for necrotizing enteritis and enterotoxemia, mostly in neonatal individuals of many animal species, including humans. ETX is the main toxin involved in enterotoxemia of sheep and goats. ITX has been implicated in cases of enteritis in rabbits and other animal species; however, its specific role in causing disease has not been proved. CPE is responsible for human food-poisoning and non-foodborne C. perfringens-mediated diarrhea. NetB is the cause of necrotic enteritis in chickens. In most cases, host-toxin interaction starts on the plasma membrane of target cells via specific receptors, resulting in the activation of intracellular pathways with a variety of effects, commonly including cell death. In general, the molecular mechanisms of cell death associated with C. perfringens toxins involve features of apoptosis, necrosis and/or necroptosis. PMID- 29786674 TI - Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition. AB - Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor. PMID- 29786675 TI - Combined Effectiveness of Honey and Immunonutrition on Bacterial Translocation Secondary to Obstructive Jaundice in Rats: Experimental Study. AB - BACKGROUND Obstructive jaundice is a serious, life-threatening condition that can lead to death as a result of sepsis and multiorgan failure due to bacterial translocation. Treatment should be started as soon as possible after diagnosis. MATERIAL AND METHODS Forty 24-week-old male Sprague Dawley rats, with an average weight of 250 g to 300 g, were included in this study. The rats were randomly placed into five groups, each group consisted of eight rats. The sham group underwent only common bile duct (CBD) dissection and no ligation was performed. CBD ligation was applied to the other groups. After the operation, one CBD group was fed with rat chow only, the others were fed with rat chow supplemented with honey, or immunonutrients, or honey plus immunonutrients. After 10 to 12 days, all rats were sacrificed; blood and tissue samples were collected for biochemical, microbiological, and histopathological evaluation. RESULTS In the groups that were fed with honey and immunonutrients, alanine aminotransferase (ALT) levels were decreased significantly compared to the other groups. Statistically significant differences were detected in terms of bacterial translocation (BT) rates among liver and spleen samples, and laboratory values of serum, except for MLNs of the BDL+HI group, when compared to other groups. We found mean mucosal thickness of ileum samples have been improved notably in the BDL+HI group compared to the other groups, especially compared to the C/BDL group. CONCLUSIONS Immunonutrition applied with honey had immunostimulant effects, decreased BT due to an additive effect, and had positive effects on intestinal mucosa. PMID- 29786676 TI - [The modern approaches to the restoration of postural balance in the patients suffering from the consequences of an acute cerebrovascular accident (CVA)]. AB - BACKGROUND: the most frequent and severe consequences of an acute cerebrovascular accident (CVA) are locomotor and coordination disorders which significantly increase the risk of falling in a static position and when walking. The methods used for the rehabilitation of the affected patients are designed in the first place to enable the patients to acquire the skills necessary for maintaining the static balance. The modern equipment allows to carry out coordination training in the static position and also during walking. AIM: The objective of the present study was to evaluate, based on the results of our original research, the feasibility and effectiveness of the application of the "Balance tutor" system developed for the restoration of static and dynamic balance in the framework of the combined rehabilitation treatment of the patients suffering from impaired postural balance as a consequence of acute cerebrovascular accident (CVA). MATERIALS AND METHODS: A total of 56 patients presenting with impaired postural balance following CVA were available for the examination. All of them underwent functional testing to assess the static and dynamic balance, walking abilities, and the risk of falling down including the study with the use of computer assisted stabilometry. RESULTS: The study has demonstrated that the inclusion of the "Balance tutor" system for the restoration of the static and dynamic balance in the combined rehabilitative treatment of the patients having postural balance disorders after the CVA reduces the risk of fall for a walking patient, improves his (her) static and dynamic balance, increases the patient's ability to move without exterior help. The patients comprising the main study group were found to experience a decrease of statokinesiogram space in the "eyes are open" position (p = 0.0576, the Mann-Whitney U test) as well as a reliable decrease of the statokinesiogram space in the "eyes are closed" position (p=0.0063, the Mann Whitney U test). Similar changes occurred in speed of pressure center relocation. By the end of the rehabilitation course, the patients of the main group exhibited a reliable enhancement in the dynamic balance rates estimated with the use of the Berg Balance Scale (p=0.028, Tukey's criterion), an increase in stability based at the Tinneti scale, p=0.0291; Tukey's criterion), and a decrease of the risk of falling during walk assessed with the application of Dynamic Gait Index scale (p = 0.0001, Tukey's criterion). DISCUSSION: The results of the present study with the inclusion of the "Balance tutor" system in the program of combined rehabilitation of the patients suffering from the consequences of CVA in the form of the postural balance impairment give evidence of the feasibility and effectiveness of this approach. There is reason to believe that its application is likely to reduce the risk of falling down and to improve characteristics of static and dynamic balance. CONCLUSION: The inclusion of the "Balance tutor" system in the program of combined rehabilitation of the patients suffering from the consequences of CVA in the form of the postural balance impairment is both feasible and effective. PMID- 29786677 TI - [Combined rehabilitation in the patients presenting with dorsopathies of the lumbar spine and concomitant irritable bowel syndrome based at a therapeutic clinic]. AB - BACKGROUND: Comorbidity constitutes a serious challenge for rehabilitative medicine. The comorbidity of the dorsopathy of the lumbar spine and irritable bowel syndrome mutually complicates the clinical course of both conditions, significantly reduces the patients' quality of life. and increases the costs of diagnostic procedures and restoration of the working capacity. The approaches to the non-pharmacological management of the patients presenting with these diseases remain to be developed. AIMS: The objective of the present study was to evaluate the effectiveness of the proposed combined non-medicinal rehabilitation modality which included a course of therapy with the application of modulated sinusoidal currents, total wrappings with the use of a Rapan saline solution, and sedative inhalations additionally introduced into the basic medicinal therapy of the patients presenting with dorsopathy of the lumbar spine combined with irritable bowel syndrome in the stationary phase. MATERIALS AND METHODS: A total of 59 patients at the age from 20 to 65 years suffering from dorsopathy of the lumbar spine and concomitant irritable bowel syndrome were examined and treated. All the patients were randomized into two groups, the main (n=21) and control (n=38) one, matched for the sex and age. The patients in the control group received the conventional medical treatment in accordance with the adopted medical and economic standards during 2 weeks. The patients of the main group received, in addition to the basal medicinal therapy, the proposed combined rehabilitative physiotherapeutic treatment that included a course of therapy with modulated sinusoidal currents, total wrapping with the use of a Rapan saline solution, and sedative inhalations of the of peony root extract. The effectiveness of these rehabilitation modalities was monitored before and after the course of therapy based on the estimation of bowel function dynamics, the severity of pain syndrome, and the patient's quality of life in terms of the health status with the use of the SF-36 questionnaire. RESULTS: The therapeutic and rehabilitative procedures resulted in a well apparent improvement of the genera condition in the patients of the main group associated with a greater degree of reduction of the incidence of specific clinical symptoms, more rapid relief of the pain syndrome, and a more pronounced improvement of the quality of life indices in comparison with the same variables in the patients comprising the control group. After the course of the treatment and rehabilitation, the incidence of spinal pain in the patients of the main group was significantly reduced by 87% (p=0.001) compared with those of the control group (32%; p=0.005). The frequency of abdominal pain decreased in the main group by 47% (p=0.021) versus the control group (by 27%; p=0.007). The quality of life indices increased 1.2 times in the main group but remained unaltered in the control group. DISCUSSION: The patients of the main group exhibited a more pronounced than in the control group positive dynamics of health conditions characterized by a well apparent reduction in the incidence of the major clinical symptoms of the disease, faster alleviation of the pain syndrome, and the marked improvement of the quality of life indices. CONCLUSIONS: The results of the study with the inclusion of therapy with modulated sinusoidal currents together with total wrapping using the Rapan saline solution and sedative inhalations into the program of the combined treatment of the patients presenting with dorsopathy of the lumbar spine and concomitant irritable bowel syndrome provide a basis for recommending this physiotherapeutic modality for personalized rehabilitation of this group of patients under conditions of a therapeutic clinic. PMID- 29786678 TI - [The feasibility of the early application of the means for the physical rehabilitation with a view to improvement of life quality in the women presenting with postmastectomy syndrome]. AB - BACKGROUND: the problem of rehabilitation and improvement of the life quality of women with the postmastectomy syndrome holds an important place in the modern concept of the treatment of breast cancer. AIM: The objective of the present study was to determine the purposefulness of the early application of the available means and methods of physical rehabilitation for the improvement of the life quality in the women presenting with postmastectomy syndrome. PATIENTS AND METHODS: The study included 135 women with the postmastectomy syndrome who had undergone radical mastectomy as described by Madden followed by postoperative radiotherapy. Fifty women were examined and treated as in-patients whereas the remaining 85 ones were out-patients under regular medical check-up The average age of the treated patients was 60.27+/-0.79 years. The in-patients were randomly subdivided into two groups: the main one (n=25) and the group of comparison (n=25). At the stage of dispensary observations, the women were also allocated to two groups: the first (n=45) and the second main groups (n=40), depending on the choice of the personality-oriented program for physical rehabilitation. The analysis of the quality of life was carried out in the beginning of the out patient rehabilitation treatment, then within 6 and 12 months after its initiation making use of the standardized Functional Assessment of Cancer Therapy (FACT-B + 4) questionnaire. RESULTS AND DISCUSSION: The benefits of the early physical rehabilitation of the in-patients first became apparent within six months after the onset of training as follows from the significantly better performance of the physical, social, emotional functions estimated taking into consideration the subscales of breast cancer and hand disorders in the women comprising the main group of the patients in comparison with those in the first and second main groups: the difference amounted to 2.34 (p<0.05), 1,88 (r<0.01), 2,52 (r<0.001), 3,52 (r<0.001) and 4,09 (r<0.001) points respectively. In a year, only the improvement of the social and emotional state persisted. CONCLUSION: The proposed personality-oriented program of physical rehabilitation can be used in the clinical practice of the relevant specialized departments for the improvement of the quality of life of the women presenting with postmastectomy syndrome. PMID- 29786679 TI - [The rationale for the application of photomagnetic therapy in the treatment of dermatitis]. AB - BACKGROUND: in spite of the fact that photomagnetic therapy with the use of the FotoSPOK device (Magnomed Ltd., Belarus) is already used in the medical practice, the application of this method for the management of many diseases remains to be substantiated on the scientifically sound grounds. AIM: The objective of the present study was to evaluate the effectiveness of photomagnetic therapy in the treatment of the local inflammatory process in the skin and to elaborate the rationale for the application of this technique in the treatment of contact dermatitis. MATERIALS AND METHODS: The experiments were carried out on 168 outbred male rats. A modified model of experimental contact dermatitis was used in the work. The course of the treatment consisted of 8 procedures lasting 20 minutes each. The character and regression of dermatitis were estimated based on the general condition of the animals and dynamics of the skin processes. Simultaneously, the cutaneous temperature was recorded and skin microcirculation assessed. The morphological changes in the skin were evaluated in the rats with experimental dermatitis that received no treatment as well as in those given a course of photomagnetic therapy, before and after its application. RESULTS: The clinical, histochemical and histological data obtained in this study give evidence that the most effective tool currently available for the treatment of experimental dermatitis is photomagnetic therapy with the use a low-frequency magnetic field in the combination with the light of the blue and green spectral regions for the elimination of the inflammatory changes and oedema and with the light of the red and yellow spectral regions for the restoration of microcirculation and stimulation of regenerative processes in the skin. CONCLUSIONS: The results of the present study can serve as the basis for the differentiated application of the light of different wavelengths in dermatology; also, they can be used for the further development of the methods of photomagnetic therapy for the treatment of the inflammatory processes in the skin. PMID- 29786680 TI - [The comprehensive evaluation of the bioclimatic comfort at the territories of the Russian Far East with reference to winter-time recreational activities and primary wellness tourism]. AB - BACKGROUND: in the framework of the current tendency toward the further development of the socio-economic sphere in the Russian Far East (RFE), the relevant investigations aimed at creating the comfortable conditions for recreational and touristic activities as well as for rehabilitative therapy of the local population acquire the increasingly greater importance. AIM: The objective of the present study was the comprehensive evaluation of the bioclimatic comfort at the territories of interest with special reference to winter-time recreational activities and primary wellness tourism. MATERIALS AND METHODS: This study was designed to evaluate the health resort, recreational, and therapeutic resources of the selected areas of the Russian Far East with special reference to the data provided by the climate monitoring stations during the periods from December to March of 1965-2014. The following methods were used for the purpose: the comparative analysis of climatic information and elementary methods of mathematical statistics. RESULTS: The evaluation of the study territory in terms of the bioclimatic comfort gave evidence that the southern regions of Primorye as well as Sakhalin island, and Kamchatka peninsula provide the most favorable conditions for the therapeutic and recreational activities, leisure and sports in the winter seasons. CONCLUSION: The analysis of the studied bioclimatic indices of comfort at different territories of the Russian Far East has demonstrated their great potential for the further development of recreation services, rehabilitation, sporting and touristic activities. The study has revealed the new opportunities for the enhancement of bioclimatic comfort of the region and for the improvement of the quality of life and employment of the local population. PMID- 29786681 TI - [The role of changes in the structure of water and water-based systems in the mechanism of combined action of the magnetic field and natural therapeutic factors]. AB - The application of the dielectrometric technology in the combination with the resonance method and thermometry has been shown to provide an insight into a variety of factors including the influence of the magnetic field of the permanent magnets on the structure of water and water-containing systems. It was found that the magnetization of both distilled water and "Karachinskaya" mineral water increase their structuredness. Magnetization changes the biological properties of therapeutic peloids by virtue of a change in the structure of water and, accordingly, the structuring of the water fraction of therapeutic muds. The analysis of the results of experimental and theoretical studies gives evidence that variations in the structure of water and water-based systems play an important role in enhancing the effectiveness of the combined treatment with the use of the magnetic field and the natural therapeutic factors. The positive and adaptogenic effects of such treatment appears to be due to such changes in the structure of water and water-containing systems which facilitate communication between the processes in the resonant mode but maintain stability of the cellular structures by limiting the mobility of water dipoles under the influence of non resonant frequencies. PMID- 29786682 TI - [The implementation of the method of enhanced external counter pulsation for the treatment of cardiovascular diseases]. AB - The cardiovascular diseases occupy a leading place in the structure of overall morbidity affecting the population not only of Russia but also of the majority of the developed countries throughout the world; they thus impose the heavy social and economic burden on both the public healthcare services and the modern society in general. At the same time, systemic atherosclerosis is considered to be one of the most common, severe, and life-threatening condition. Despite the presence of a large number of pharmaceutical and surgical methods for the treatment of this pathology, they are not infrequently lacking the desired effectiveness. The use of the shunting operations and endovascular methods failed to radically resolve the problem of managing systemic atherosclerosis and atherosclerosis of the lower limbs. A relatively novel approach which currently begins to find the ever increasing application for the treatment of patients presenting with cardiovascular pathology is based on the enhanced external counter-pulsation method although both the clinical and theoretical prerequisites of its application were developed rather long ago. This non-invasive therapeutic method allows to increase the perfusion pressure in the coronary arteries in diastole and to reduce the resistance to the cardiac ejection in the systole. The objective of this review article was to perform the analysis of the available literature publications on the use of the enhanced external counter-pulsation technique for the treatment of the patients presenting with the diseases of the cardiovascular system and to evaluate the clinical effectiveness of this approach as well as the availability of the treatment for the patients. PMID- 29786683 TI - [The application of kinesiotaping for the rehabilitation of the post-stroke patients]. AB - This review of the scientific literature was designed to consider the prospects for the application of kinesiotaping for the rehabilitation of the post-stroke patients. The relevance of the work arises from the absence of a systemic analysis of the large number of investigations that have been carried out during the past two years. The objective of the present review article was to evaluate the influence of kinesiotaping on the health status of the post-stroke patients and the course of their rehabilitative treatment based on the results of analysis of the scientific reports published during the period from 2015 to 2017. The analysis has demonstrated that the method under consideration makes it possible to effectively reduce spasticity, increase the paretic limb power, improve the static and dynamic balance, and alleviate the pain syndrome by virtue of the ability to improve the articulation proprioception and to regulate the muscle tone. Such effects are known to promote the reduction of muscle tone asymmetry in the patients suffering from hemiparesis and articulation instability which in its turn improves the patients' gait and walking ability, hightens their living standards, and allows to tolerate enhanced physical exertion. Kinesiotaping actually improves the locomotor function in the post-stroke patients Taken together, the advantages of the approach in question give reason to recommend kinesiotaping for the wide application for the combined rehabilitative treatment of the post-stroke patients. PMID- 29786684 TI - [The development of the system of medical rehabilitation based at the Russian health resort facilities: investment prospects]. AB - The present work is devoted to the prospects for attracting investments for the maintenance and development of the medical rehabilitation practices based at the Russian health resort facilities. The article describes the prerequisites for the enhancement of the investment attractiveness of the development of the system of medical rehabilitation in the said institutions including the formulation and strengthening of the legal and regulatory framework, the capacity for the organization of the second and third stages of medical rehabilitation in the existing spa and health resort facilities, the attraction of the funds of compulsory medical insurance as an additional source of the financial support. The main legal documents regulating the organization and provision of medical rehabilitation based at the spa and health resort facilities are presented. The results of the implementation of the investment concept of the development of medical rehabilitation in the framework of the system of health resort treatment as exemplified by the experience of JSC "The group of companies "Medsi" are discussed. It is shown that the development of medical rehabilitation based at the spa and health resort facilities greatly contributes to the significant expansion of the potential customer base and promotes the further growth of business scale. PMID- 29786686 TI - Author Correction: Rapid signal enhancement method for nanoprobe-based biosensing. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29786685 TI - Regulation of chromatin states and gene expression during HSN neuronal maturation is mediated by EOR-1/PLZF, MAU-2/cohesin loader, and SWI/SNF complex. AB - Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution. Our results demonstrated that chromatin composition in the promoter region of several genes acting for neuronal terminal maturation was modulated at an early developmental stage, and is dependent on the function of the transcription factor EOR-1/PLZF and the cohesin loader MAU 2/MAU2. Components of the SWI/SNF chromatin remodeling complex were also required for the proper expression of terminal maturation genes. Epistasis analyses suggested that eor-1 functions with mau-2 and swsn-1 in the same genetic pathway to regulate the maturation of HSNs. Collectively, our study provides a novel approach to analyze neuronal maturation and proposes that predefined epigenetic modifications, mediated by EOR-1, MAU-2, and the SWI/SNF complex, are important for the preparation of future gene expression programs in neuronal terminal maturation. PMID- 29786688 TI - What's in a name? PMID- 29786687 TI - Genome-wide analysis of circular RNAs in bovine cumulus cells treated with BMP15 and GDF9. AB - Circular RNAs (circRNAs) are important members of the non-coding RNA family, and those relating to animal physiologies have been widely studied in recent years. This study aimed to explore the roles of circRNAs in the regulation of follicular development. We constructed four bovine cumulus cell cDNA libraries, including a negative control group (NC) and groups treated with BMP15, GDF9 and BMP15 + GDF9, and we sequenced the libraries on the Illumina HiSeq Xten platform. We identified 1706 circRNAs and screened for differential circRNA expression. We conducted a bioinformatics analysis of these circRNAs and screened for differential circRNAs. Functional annotation and enrichment analysis of the host genes showed that the differential circRNAs were related to locomotion, reproduction, biological adhesion, growth, rhythmic processes, biological phases and hormone secretion. According to the differential expression of circRNA between groups, there were 3 up-regulated and 6 down-regulated circRNAs in the BMP15 group as well as 12 up regulated and 24 down-regulated circRNAs in the GDF9 group. Co-addition of both BMP15 and GDF9 resulted in 15 up-regulated and 13 down-regulated circRNAs. circ_n/a_75,circ_12691_1 and circ_n/a_303 were altered in both the BMP15 and GDF9 groups as well as in the BMP15 + GDF9 combination group. We focused on these three circRNAs because they were potentially associated with the additive effect of BMP15 and GDF9. Quantitative PCR analysis showed that the expression levels of these three circRNAs were consistent with the sequencing results. In addition, the target miRNAs of circ_n/a_75 and circ_n/a_303, miR-339a, miR-2400 and miR 30c, were down-regulated in the experimental group, which was in contrast to the circRNAs trend. These findings demonstrated that BMP15 and GDF9 may regulate the target gene through circRNA, as a miRNA sponge, in order to regulate the status of bovine cumulus cells and affect follicular development. PMID- 29786690 TI - Corrigendum: HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity. AB - This corrects the article DOI: 10.1038/srep40037. PMID- 29786689 TI - Gridded birth and pregnancy datasets for Africa, Latin America and the Caribbean. AB - Understanding the fine scale spatial distribution of births and pregnancies is crucial for informing planning decisions related to public health. This is especially important in lower income countries where infectious disease is a major concern for pregnant women and new-borns, as highlighted by the recent Zika virus epidemic. Despite this, the spatial detail of basic data on the numbers and distribution of births and pregnancies is often of a coarse resolution and difficult to obtain, with no co-ordination between countries and organisations to create one consistent set of subnational estimates. To begin to address this issue, under the framework of the WorldPop program, an open access archive of high resolution gridded birth and pregnancy distribution datasets for all African, Latin America and Caribbean countries has been created. Datasets were produced using the most recent and finest level census and official population estimate data available and are at a resolution of 30 arc seconds (approximately 1 km at the equator). All products are available through WorldPop. PMID- 29786692 TI - Corrigendum: Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers. AB - This corrects the article DOI: 10.1038/srep45170. PMID- 29786691 TI - Prognosis and nomogram for predicting postoperative survival of duodenal adenocarcinoma: A retrospective study in China and the SEER database. AB - As primary duodenal adenocarcinoma is rare, the prognostic factors of this disease remain insufficiently explored, especially in China. We identified postoperative duodenal adenocarcinoma patients at a Chinese double-center (from 2006 to 2016) or who were registered with the Surveillance, Epidemiology, and End Results (SEER) database (from 2004 to 2014). Clinicopathological features and significant prognostic factors for cancer-specific survival (CSS) were reviewed and analyzed by using univariate and multivariate Cox proportional hazards regression. Then, a nomogram predicting CSS was constructed based on the SEER database and validated externally by using the separate Chinese cohort. Totally, 137 patients from the Chinese double-center and 698 patients from the SEER database were included for analysis. The multivariate analyses showed that age, tumor grade and TNM stage were independent prognostic factors. The nomogram constructed using these factors showed a clear prognostic superiority to the AJCC TNM classification, 7th ed. (C-index: SEER cohort, 0.693 vs 0.625, P < 0.001; Chinese cohort, 0.677 vs 0.659, P < 0.001, respectively). In summary, the valuable prognostic factors in patients with duodenal adenocarcinoma were age, tumor grade and TNM stage. This study developed a nomogram that can precisely predict the CSS for postoperative duodenal adenocarcinoma patients. PMID- 29786693 TI - HormoneBase, a population-level database of steroid hormone levels across vertebrates. AB - Hormones are central regulators of organismal function and flexibility that mediate a diversity of phenotypic traits from early development through senescence. Yet despite these important roles, basic questions about how and why hormone systems vary within and across species remain unanswered. Here we describe HormoneBase, a database of circulating steroid hormone levels and their variation across vertebrates. This database aims to provide all available data on the mean, variation, and range of plasma glucocorticoids (both baseline and stress-induced) and androgens in free-living and un-manipulated adult vertebrates. HormoneBase (www.HormoneBase.org) currently includes >6,580 entries from 476 species, reported in 648 publications from 1967 to 2015, and unpublished datasets. Entries are associated with data on the species and population, sex, year and month of study, geographic coordinates, life history stage, method and latency of hormone sampling, and analysis technique. This novel resource could be used for analyses of the function and evolution of hormone systems, and the relationships between hormonal variation and a variety of processes including phenotypic variation, fitness, and species distributions. PMID- 29786694 TI - Spin supersolid phase in coupled alternating spin chains. AB - We study the ground state phase diagram of a two dimensional mixed-spin system of coupled alternating spin-1 and 1/2 chains with a stripe supersolid phase. Utilizing different analytical and numerical approaches such as mean field approximation, cluster mean field theory and linear spin wave theory, we demonstrate that our system displays a rich ground state phase diagram including novel stripe supersolid, solids with different fillings and super-counterfluid phases, in addition to a stripe solid with half filling, superfluid and Mott insulating phases. In order to find a minimal mixed-spin model for stripe supersolidity, in the second part of the paper we consider two kinds of mixed spin system of coupled alternating spin-1 and 1/2 chains with (i) anisotropic nearest neighbor interactions, (ii) anisotropic hoppings and study their ground state phase diagrams. We demonstrate that, for the systems with uniform hoppings, the repulsive intra-chains interactions are necessary for stripe supersolidity. In this case the minimal two dimensional mixed-spin model is a system of spin-1 and spin-1/2 XXZ chains, interacting via Ising Hamiltonian. In the case of anisotropic hoppings, a system of coupled Ising chains is the minimal model. PMID- 29786695 TI - The asthma mobile health study, smartphone data collected using ResearchKit. AB - Widespread adoption of smart mobile platforms coupled with a growing ecosystem of sensors including passive location tracking and the ability to leverage external data sources create an opportunity to generate an unprecedented depth of data on individuals. Mobile health technologies could be utilized for chronic disease management as well as research to advance our understanding of common diseases, such as asthma. We conducted a prospective observational asthma study to assess the feasibility of this type of approach, clinical characteristics of cohorts recruited via a mobile platform, the validity of data collected, user retention patterns, and user data sharing preferences. We describe data and descriptive statistics from the Asthma Mobile Health Study, whereby participants engaged with an iPhone application built using Apple's ResearchKit framework. Data from 6346 U.S. participants, who agreed to share their data broadly, have been made available for further research. These resources have the potential to enable the research community to work collaboratively towards improving our understanding of asthma as well as mobile health research best practices. PMID- 29786698 TI - A reconstruction of global hydroclimate and dynamical variables over the Common Era. AB - Hydroclimate extremes critically affect human and natural systems, but there remain many unanswered questions about their causes and how to interpret their dynamics in the past and in climate change projections. These uncertainties are due, in part, to the lack of long-term, spatially resolved hydroclimate reconstructions and information on the underlying physical drivers for many regions. Here we present the first global reconstructions of hydroclimate and associated climate dynamical variables over the past two thousand years. We use a data assimilation approach tailored to reconstruct hydroclimate that optimally combines 2,978 paleoclimate proxy-data time series with the physical constraints of an atmosphere-ocean climate model. The global reconstructions are annually or seasonally resolved and include two spatiotemporal drought indices, near-surface air temperature, an index of North Atlantic variability, the location of the intertropical convergence zone, and monthly Nino indices. This database, called the Paleo Hydrodynamics Data Assimilation product (PHYDA), will provide a critical new platform for investigating the causes of past climate variability and extremes, while informing interpretations of future hydroclimate projections. PMID- 29786697 TI - Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes. AB - Oxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized 13C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species accumulation) in vivo. In this study, we applied these imaging probes to the normal rat brain and a rat model of glutathione depletion. We first studied hyperpolarized [1-13C]dehydroascorbate in the normal rat brain, demonstrating its robust conversion to [1-13C]vitamin C, consistent with rapid transport of the oxidized form across the blood-brain barrier. We next showed that the kinetic rate of this conversion decreased by nearly 50% after glutathione depletion by diethyl maleate treatment. Finally, we showed that dehydroascorbate labeled for positron emission tomography, namely [1 11C]dehydroascorbate, showed no change in brain signal accumulation after diethyl maleate treatment. These results suggest that hyperpolarized [1 13C]dehydroascorbate may be used to non-invasively detect oxidative stress in common disorders of the brain. PMID- 29786696 TI - Crystal structure of dihydrodipicolinate reductase (PaDHDPR) from Paenisporosarcina sp. TG-14: structural basis for NADPH preference as a cofactor. AB - Dihydrodipicolinate reductase (DHDPR) is a key enzyme in the diaminopimelate- and lysine-synthesis pathways that reduces DHDP to tetrahydrodipicolinate. Although DHDPR uses both NADPH and NADH as a cofactor, the structural basis for cofactor specificity and preference remains unclear. Here, we report that Paenisporosarcina sp. TG-14 PaDHDPR has a strong preference for NADPH over NADH, as determined by isothermal titration calorimetry and enzymatic activity assays. We determined the crystal structures of PaDHDPR alone, with its competitive inhibitor (dipicolinate), and the ternary complex of the enzyme with dipicolinate and NADPH, with results showing that only the ternary complex had a fully closed conformation and suggesting that binding of both substrate and nucleotide cofactor is required for enzymatic activity. Moreover, NADPH binding induced local conformational changes in the N-terminal long loop (residues 34-59) of PaDHDPR, as the His35 and Lys36 residues in this loop interacted with the 2' phosphate group of NADPH, possibly accounting for the strong preference of PaDHDPR for NADPH. Mutation of these residues revealed reduced NADPH binding and enzymatic activity, confirming their importance in NADPH binding. These findings provide insight into the mechanism of action and cofactor selectivity of this important bacterial enzyme. PMID- 29786700 TI - Corrigendum: Global effects of local food-production crises: a virtual water perspective. AB - This corrects the article DOI: 10.1038/srep18803. PMID- 29786701 TI - Lutembacher syndrome with mitral valve calcification in a 31-year old male. AB - Lutembacher syndrome is characterized by a congenital ostium secundum atrial septal defect and an acquired mitral valve stenosis. We present a similar case in a 31-year old male who came in with orthopnoea, central cyanosis and pedal oedema. Examination revealed cardiac murmurs in tricuspid and apical regions. Chest x-ray showed signs of pulmonary congestion and ventricular enlargement. Electrocardiogaphy (ECG) revealed right axis deviation and right bundle branch block along with atrial fibrillation and Transthoracic Echocardiography (TTE) showed abnormal valves (mitral stenosis with calcification and tricuspid regurgitation) and dilated cardiac chambers. The patient was consequently treated with beta-blockers and diuretics and scheduled for valvular and septal repair via open heart surgery. The purpose of this case report is to assist cardiologists in diagnosing this syndrome accurately on the basis of symptoms and investigations. PMID- 29786699 TI - The draft genome sequence of cork oak. AB - Cork oak (Quercus suber) is native to southwest Europe and northwest Africa where it plays a crucial environmental and economical role. To tackle the cork oak production and industrial challenges, advanced research is imperative but dependent on the availability of a sequenced genome. To address this, we produced the first draft version of the cork oak genome. We followed a de novo assembly strategy based on high-throughput sequence data, which generated a draft genome comprising 23,347 scaffolds and 953.3 Mb in size. A total of 79,752 genes and 83,814 transcripts were predicted, including 33,658 high-confidence genes. An InterPro signature assignment was detected for 69,218 transcripts, which represented 82.6% of the total. Validation studies demonstrated the genome assembly and annotation completeness and highlighted the usefulness of the draft genome for read mapping of high-throughput sequence data generated using different protocols. All data generated is available through the public databases where it was deposited, being therefore ready to use by the academic and industry communities working on cork oak and/or related species. PMID- 29786702 TI - Color stability, psychosocial impact, and effect on self-perception of esthetics of tooth whitening using low-concentration (6%) hydrogen peroxide. AB - OBJECTIVE: The aim of this study was to assess the bleaching efficacy and impact on psychosocial and esthetics self-perception of a low-concentration (6%) hydrogen peroxide (H2O2) gel compared with a conventional (37.5%) H2O2 gel when used as an in-office treatment. METHOD AND MATERIALS: In total, 35 participants received two sessions of three 12-minute applications of treatment with 37.5% H2O2 on one side of the mouth and 6% H2O2 on the other. Color changes were measured objectively using total variation in color (DeltaE) and subjectively using Vita Classical scale (DeltaSGU). The Psychosocial Impact of Dental Aesthetic Questionnaire (PIDAQ) and Oral Health Impact Profile (OHIP-14) esthetic questionnaires were administered to measure self-perception and the psychosocial impact of the whitening procedure. RESULTS: Both gels produced significant changes in tooth color at 1 and 3 months post-whitening. The objective efficacy (DeltaE) of 37.5% H2O2 (9.06 +/- 2.96) was significantly higher than that of 6% H2O2 (5.69 +/- 3.06). The results of the subjective assessment were not statistically different. There was a positive impact on esthetic auto perception (OHIP-14, P < .05) and psychosocial impact (PIDAQ, P < .05) at the 3-month time point. CONCLUSION: Low concentration of H2O2 (6%) achieved effective bleaching (DeltaE > 5 units) with good stability at 3 months accompanied by a positive psychosocial impact and enhanced self-perception. However, the traditional 35% concentration was objectively more effective. PMID- 29786703 TI - 12 years' preservation of maxillary permanent incisors with cervical root fractures adjacent to aggressive periodontitis: Report of a case. AB - This case report presents long-term results following horizontal root fracture of both maxillary central incisors in a 19-year-old woman with aggressive periodontitis. Due to extensive marginal bone loss and the close proximity of the fracture lines to the bottoms of the periodontal pockets, the prognosis of both teeth was uncertain at the time of the accident. Nevertheless, a conservative treatment strategy consisting of splinting and nonsurgical periodontal therapy was initiated. Follow-up at 12 years after the start of treatment revealed a stable situation from clinical and radiologic perspectives. Permanent fixation to the adjacent teeth and regular supportive periodontal care were the basis for a favorable long-term prognosis. PMID- 29786704 TI - Peri-implant tissue score (PITS) as a measure of success, applied to 869 dental implants from a retrospective clinical study. AB - OBJECTIVE: This article presents a methodology of a comprehensive score for assessment and monitoring of dental implant success from the peri-implant tissue perspective. It involves only standard and minimally invasive techniques accessible to general dental practices, without the need for special equipment. METHODS AND MATERIALS: The proposed score methodology combines existing consensual global knowledge regarding aspects of dental implant success with the standard examination tools accepted for regular recall assessment. The score is a sum of five three-grade parameters: bone level, peri-implant inflammation, amount of attached mucosa, tissues recession (ie, exposure of implant components to intraoral environment), and the horizontal buccal profile of the alveolar process. The name peri-implant tissue score (PITS) is derived from the intended primary use of monitoring the state of implants and the surrounding hard and soft tissues. With its emphasis on buccal-aspect tissues, the score is designed to aid the detection of early signs of tissues deterioration. RESULTS: The use of the score is demonstrated on a sample pool of 869 retrospectively evaluated implants with airborne-particle-abraded, acid-etched surfaces with time in service from 0 to 12 years. The parameters constituting the score were statistically tested on correlation with a reference set of success criteria, on mutual cross correlations, and on the invariance to the implants' time-in-service. The PITS demonstrated to be highly representative of the success criteria, offering a fine scale from 0 to 10, and reversibility. CONCLUSION: The PITS withstood the tests. It responds to an existing need in the field, is widely accessible and inexpensive, and, thus, shows promise for use in general dental practice. PMID- 29786706 TI - Hg(ii) interactions with T-rich regions in oligonucleotides: effects of positional variations on the electrochemical properties. AB - Hg(ii) binding to thymine-rich oligonucleotides (ODNs) is investigated electrochemically. The focus of this study is to probe the effects of position on the electrochemical response. For this purpose, three oligonucleotides were investigated in which the position of a hexa-thymine repeat is varied within a surface-supported oligonucleotide. The hexa repeats were placed in the top, middle, and bottom positions within the strand with respect to the gold surface. The effects were monitored by electrochemical impedance spectroscopy and scanning electrochemical microscopy. Using charge transfer resistance (RCT) and tip current (I) as a measure, it was possible to monitor the effects of Hg(ii) binding to the ds-oligonucleotide. The extent of film resistance reduces as the T rich region moves from the bottom to top position within the film. The T-rich region closer to the gold surface probably builds less flexible and more rigid T Hg(ii)-T basepairs compared to the other two positions and is expected to stay in the upright orientation on the surface. This in turn results in significant differences in the electrochemical readout, demonstrating that the position of T rich sequences within an oligonucleotide strand matters. PMID- 29786707 TI - Biocompatible alkyl cyanoacrylates and their derivatives as bio-adhesives. AB - Cyanoacrylate adhesives and their homologues have elicited interest over the past few decades owing to their applications in the biomedical sector, extending from tissue adhesives to scaffolds to implants to dental material and adhesives, because of their inherent biocompatibility and ability to polymerize solely with moisture, thanks to which they adhere to any substrate containing moisture such as the skin. The ability to tailor formulations of alkyl cyanoacrylate to form derivative compounds to meet application requirements along with their biodegradability in conjunction with their inherent biocompatibility make them highly sought after candidates in the biomedical sector. There has been extensive exploration of cyanoacrylate adhesives and their homologue systems in biomedical applications, but no consolidated literature of the vast data is available. The ability of cyanoacrylate adhesives to cure at low temperatures and without the need for any hardener, which is attributed to the high-strength bonding interaction between two non-amalgamating substrates, with their ease of dispersion and self-curing, avoids the curtailing of the effective utilization of such adhesives in biomedical engineering applications as bio glues for amalgamating tissues, implants, scaffolds etc. This article consolidates copious work on cyanoacrylate adhesives and their derived systems which are functional in versatile biomedical engineering applications such as bio glues, dental material and adhesives and other potential applications. PMID- 29786708 TI - Platforms for rapid cancer characterization by ambient mass spectrometry: advancements, challenges and opportunities for improvement towards intrasurgical use. AB - Ambient Mass Spectrometry (MS) analysis is widely used to characterize biological and non-biological samples. Advancements that allow rapid analysis of samples by ambient methods such as Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) and Rapid Evaporative Ionization Mass Spectrometry (REIMS) are discussed. A short, non-comprehensive overview of ambient MS is provided that only contains example applications due to space limitations. A spatially encoded mass spectrometry analysis concept to plan cancer resection is introduced. The application of minimally destructive tissue ablation probes to survey the surgical field for sites of pathology using on-line analysis methods is discussed. The technological challenges that must be overcome for ambient MS to become a robust method for intrasurgical pathology assessments are reviewed. PMID- 29786712 TI - Cocrystals of a 1,2,4-thiadiazole-based potent neuroprotector with gallic acid: solubility, thermodynamic stability relationships and formation pathways. AB - Three distinct solid forms, namely anhydrous cocrystals with 2 : 1 and 1 : 1 drug/acid ratios ([TDZ : GA] (2 : 1), [TDZ : GA] (1 : 1)), and a hydrated one having 1 : 1 : 1 drug/acid/water stoichiometry ([TDZ : GA : H2O] (1 : 1 : 1)), have been formed by cocrystallization of the biologically active 1,2,4 thiadiazole derivative (TDZ) with gallic acid (GA). The thermodynamic stability relationships between the cocrystals were rationalized in terms of Gibbs energies of the formation reactions and further verified by performing a set of competitive and exchange mechanochemical reactions. Interestingly, competitive grinding in the presence of the structurally related vanillic acid led to the formation of a new polymorphic form of the [TDZ : Vanillic acid] (1 : 1) cocrystal, which was promoted by gallic acid. The mechanochemical method was also applied to elucidate the alternative pathways of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal formation. Direct cocrystallization of TDZ with GA monohydrate was found to proceed much faster than the reaction of TDZ and anhydrous GA in the presence of an acetonitrile/water mixture, which may indicate the presence of a transitional stage. According to dissolution studies, the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal was ca. 6.6 times more soluble than the parent 1,2,4-thiadiazole at pH 2.0 and 25.0 degrees C. The apparent two-step dehydration behavior of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal monohydrate was clarified by analyzing the intermolecular interactions of water molecules with the crystalline environment derived from solid state DFT calculations. PMID- 29786710 TI - Direct observation of the oxidation of DNA bases by phosphate radicals formed under radiation: a model of the backbone-to-base hole transfer. AB - In irradiated DNA, by the base-to-base and backbone-to-base hole transfer processes, the hole (i.e., the unpaired spin) localizes on the most electropositive base, guanine. Phosphate radicals formed via ionization events in the DNA-backbone must play an important role in the backbone-to-base hole transfer process. However, earlier studies on irradiated hydrated DNA, on irradiated DNA-models in frozen aqueous solution and in neat dimethyl phosphate showed the formation of carbon-centered radicals and not phosphate radicals. Therefore, to model the backbone-to-base hole transfer process, we report picosecond pulse radiolysis studies of the reactions between H2PO4 with the DNA bases - G, A, T, and C in 6 M H3PO4 at 22 degrees C. The time-resolved observations show that in 6 M H3PO4, H2PO4 causes the one-electron oxidation of adenine, guanine and thymine, by forming the cation radicals via a single electron transfer (SET) process; however, the rate constant of the reaction of H2PO4 with cytosine is too low (<107 L mol-1 s-1) to be measured. The rates of these reactions are influenced by the protonation states and the reorganization energies of the base radicals and of the phosphate radical in 6 M H3PO4. PMID- 29786713 TI - In situ fabrication of hollow ZnO@NC polyhedra from ZIF-8 for the determination of trace Cd(ii). AB - In this work, a novel electrochemical sensor for Cd(ii) detection with differential pulse anodic stripping voltammetry (DPASV) is fabricated based on hollow ZnO@nitrogen-doped carbon (H-ZnO@NC) polyhedra, which are prepared from ZIF-8 via in situ tannic acid etching and a subsequent calcination process. The as-obtained H-ZnO@NC exhibits a polyhedral morphology with a well-defined hollow structure and a uniform distribution of elements C, N, O, and Zn in the shell. The unique structure of H-ZnO@NC can provide an enlarged surface area and abundant active sites. Moreover, ZnO has a strong affinity for heavy metals, which can enhance the adsorption capacity of H-ZnO@NC for Cd(ii) in the accumulation step of stripping voltammetry, and thus improve the electrochemical sensing performances. As expected, the H-ZnO@NC-based sensor achieves a wide linear range of 0.3-300 MUg L-1, a low detection limit of 0.1 MUg L-1 (S/N = 3), and exhibits good selectivity as well as high stability and reproducibility. Moreover, the proposed electrochemical sensor can be applied for the determination of Cd(ii) in real water samples, obtaining satisfactory results. PMID- 29786715 TI - Cancer cell membrane-coated magnetic nanoparticles for MR/NIR fluorescence dual modal imaging and photodynamic therapy. AB - Theranostic nanoprobes integrated with dual-modal imaging and therapeutic functions, such as photodynamic therapy (PDT), have exhibited significant potency in cancer treatments due to their high imaging accuracy and non-invasive advantages for cancer elimination. However, biocompatibility and highly efficient accumulation of these nanoprobes in tumor are still unsatisfactory for clinical application. In this study, a photosensitizer -loaded magnetic nanobead with surface further coated with a layer of cancer cell membrane (SSAP-Ce6@CCM) was designed to improve the biocompatibility and cellular uptake and ultimately achieve enhanced MR/NIR fluorescence imaging and PDT efficacy. Compared with similar nanobeads without CCM coating, SSAP-Ce6@CCM showed significantly enhanced cellular uptake, as evidenced by Prussian blue staining, confocal laser scanning microscopy (CLSM) and flow cytometric analysis. Consequently, SSAP-Ce6@CCM displayed a more distinct MR/NIR imaging ability and more obvious photo cytotoxicity towards cancer cells under 670 nm laser irradiation. Furthermore, the enhanced PDT effect benefited from the surface coating of cancer cell membrane was demonstrated in SMMC-7721 tumor-bearing mice through tumor growth observation and tumor tissue pathological examination. Therefore, this CCM disguised nanobead that integrated the abilities of MR/NIR fluorescence dual modal imaging and photodynamic therapy might be a promising theranostic platform for tumor treatment. PMID- 29786716 TI - Unexpected protonation state of Glu197 discovered from simulations of tacrine in butyrylcholinesterase. AB - Butyrylcholinesterase (BChE) has been actively involved in drug discoveries from many fields for decades. In the crystal structure of the BChE-tacrine complex, there is an unanticipated formyl-proline molecule resolved very close to tacrine, raising an essential question on how reliable it is to apply the binding pose in a crystal structure to analyze related experimental observations, in which no formyl-proline is actually involved. In this study, by performing a series of 100 ns molecular dynamics simulations, we demonstrate that it is safe to employ the structural information from this crystal structure to analyze related experimental observations. Surprisingly, Glu197 needs to be protonated to have the structures simulated appropriately. It should be noted that Glu197 has been commonly considered as deprotonated in diverse analyses due to its low pKa in aqueous solution, for which some interpretations are inconsistent or unclear. Our further investigation shows that the protonated Glu197 plays a very important role in preserving His438 within the catalytic triad through stabilizing a highly conserved water molecule. Interestingly, the catalytic triad and Glu197 have been long recognized for possibly deviating largely from the crystal structure, which might be catalytically deficient and is generally considered to result from the difference between the crystal and aqueous environment. Herein, our results suggest that the large deviations of the catalytic triad and Glu197 from the crystal structure are caused by the inappropriate protonation state of Glu197. This finding shall provide an important clue that has been long missing for a better understanding of BChE-related puzzles or even reconsideration of some BChE catalyzed reaction mechanisms. PMID- 29786717 TI - Comparison of hydroxycarboxylato imidazole molybdenum(iv) complexes and nitrogenase protein structures: indirect evidence for the protonation of homocitrato FeMo-cofactors. AB - Glycolato and R,S-lactato imidazole molybdenum(iv) complexes [Mo3SO3(glyc)2(im)5].im.H2O (1), Na2[Mo3SO3(R,S-lact)3(im)3].10H2O (2), and [Mo6O10(R,S-lact)2(im)10].16H2O (3) have been isolated and characterized (H2glyc = glycolic acid, H2lact = lactic acid, im = imidazole). alpha-Alkoxy coordination with molybdenum [Mo-Oalpha-alkoxy 1.993(7)av A] in 1 and 2 showed obvious differences to their counterpart with alpha-hydroxy coordination [MoIV3S4(PPh3)3(Hlact)2(lact)] [2.204(4)av A] as shown in M. N. Sokolov, S. A. Adonin, A. V. Virovets, P. A. Abramov, C. Vicent, R. Llusar and V. P. Fedin, Inorg. Chim. Acta, 2013, 395, 11-18. This was also true for the 36 reported structures of FeMo-cofactors in the RCSB protein data bank (Mo-Oav 2.272 A), which can serve as indirect evidence for the protonation of homocitrate in FeMo co. The C-OHalpha-hydroxy bonds were longer than the short C-Oalpha-alkoxy bonds. Trinuclear Mo3SO3 cores were stabilized by imidazoles and/or alpha hydroxycarboxylates, whereas only two glycolates were present in 1. alpha Hydroxycarboxylates in 1 and 2 acted as bidentate ligands of Mo(iv) atoms through alpha-alkoxy and alpha-carboxy groups, while the imidazoles coordinated monodentately with nitrogen atoms. The lactates in 3 coordinated with Mo(iv) atoms through two oxygen atoms of alpha-carboxy groups, leaving the alpha-hydroxy group free. Furthermore, novel hexanuclear oxomolybdenum(v) malate Na6[(Mo2O4)3(mal)4].5H2O (4) was also isolated (H3mal = malic acid). Solid-state and solution 13C NMR resonances of carbon atoms in alpha-alkoxy groups appeared in a high-field region (71.6, 77.4 ppm), indicating that alpha-alkoxy groups were easy to protonate. PMID- 29786720 TI - A strain induced subwavelength-structure for a haze-free and highly transparent flexible plastic substrate. AB - This paper presents a method to produce subwavelength-scale (<250 nm) AgCl nanostructures on a flexible plastic film, which is indispensable for highly efficient flexible displays. Using Cl2 plasma treatment on an Ag-coated plastic film, AgCl nanostructures were produced through the reaction of Ag atoms with Cl radicals. During the reaction, the volume of AgCl expands, leading to drastically changed surface morphology from a two-dimensional (2D) flat Ag surface to a 3D subwavelength-scale AgCl nanostructure. The optical properties of AgCl on the plastic film were remarkably enhanced from 89.6% to 93.4% and the average transmittance ranged between 400 and 800 nm, while the average haze was retained below 0.3%. Consequently, OLEDs based on the subwavelength-scale AgCl nanostructure had an enhanced luminance efficiency (88.6 cd A-1 at 1000 cd m-2) of up to 10.7% without modifying the angular emission pattern, superior to that of the as-received PI film (efficiency of 80.0 cd A-1). The nanostructure enhances the transmission of electromagnetic (EM) waves as well as prohibits the scattering of EM waves, which was confirmed by finite-difference time-domain simulation and rigorous coupled wave analysis. PMID- 29786719 TI - Energy transfer chemiluminescence for ratiometric pH imaging. AB - Chemiluminescence imaging offers a low background and high sensitivity approach to imaging analytes in living cells and animals. Intensity-based measurements have been developed, but require careful consideration of kinetics, probe localization, and fluctuations in quantum yield, all of which complicate quantification. Here, we report a ratiometric strategy for quantitative chemiluminescence imaging of pH. The strategy relies on an energy transfer cascade of chemiluminescence emission from a spiroadamantane 1,2-dioxetane to a ratiometric pH indicator via fluorescent dyes in Enhancer solutions. Monitoring the pH-dependent changes in chemiluminescence emission at multiple wavelengths enables ratiometric imaging and quantification of pH independent from variations due to kinetics and probe concentration. PMID- 29786721 TI - Versatile organoaluminium catalysts based on heteroscorpionate ligands for the preparation of polyesters. AB - A series of alkyl aluminium complexes based on heteroscorpionate ligands were designed as catalysts for the ring-opening polymerisation of cyclic esters and ring-opening copolymerisation of epoxides and anhydrides. Treatment of AlX3 (X = Me, Et) with ligands bpzbeH [bpzbe = 1,1-bis(3,5-dimethylpyrazol-1-yl)-3,3 dimethyl-2-butoxide], bpzteH [bpzte = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para tolylethoxide], and (R,R)-bpzmmH [(R,R)-bpzmm = (1R)-1-{(1R)-6,6-dimethyl bicyclo[3.1.1]-2-hepten-2-yl}-2,2-bis(3,5-dimethylpyrazol-1-yl)ethoxide] for 2 hours at 0 degrees C afforded the mononuclear dialkyl aluminium complexes [AlMe2{kappa2-bpzbe}] (1), [AlEt2{kappa2-bpzbe}] (2), [AlMe2{kappa2-(R,R)-bpzmm}] (3) and [AlEt2{kappa2-(R,R)-bpzmm}] (4), and the dinuclear dialkyl complexes [AlMe2{kappa2-bpzte}]2 (5) and [AlEt2{kappa2-bpzte}]2 (6). The molecular structures of the new complexes were determined by spectroscopic methods and confirmed by X-ray crystallography. The alkyl-containing aluminium complexes can act as highly efficient single-component initiators for the ring-opening polymerisation of epsilon-caprolactone and l-lactide and for the ring-opening copolymerisation of cyclohexene oxide and phthalic anhydride to give a range of biodegradable polyesters. PMID- 29786722 TI - An urchin-like MgCo2O4@PPy core-shell composite grown on Ni foam for a high performance all-solid-state asymmetric supercapacitor. AB - In recent years, the electrochemical properties of supercapacitors have been greatly improved due to continuous improvement in their composite materials. In this study, an urchin-like MgCo2O4@PPy/NF (MgCo2O4@polypyrrole/Ni foam) core shell structure composite material was successfully developed as an electrode for supercapacitors. The MCP-2 composite material, obtained by a hydrothermal method and in situ chemical oxidative polymerization, shows a high specific capacitance of 1079.6 F g-1 at a current density of 1 A g-1, which is much higher than that of MC (783.6 F g-1) under the same conditions. Simultaneously, it has low resistance and an excellent cycling stability of 97.4% after 1000 cycles. Furthermore, an all-solid-state asymmetric supercapacitor (ASC) was assembled using MCP-2 as the positive electrode and activated carbon (AC) as the negative electrode. The MCP-2//AC ASC exhibits high specific capacitance (94 F g-1 at a current density of 0.4 A g-1), high energy density (33.4 W h kg-1 at a power density of 320 W kg-1), high volumetric energy density (17.18 mW h cm-3 at a volumetric power density of 0.16 W cm-3) and excellent cycling stability (retaining 91% of the initial value after 10 000 cycles). Simultaneously, the device has low leakage current and excellent self-discharge characteristics. All these results indicate that the MCP-2//AC ASC is a good energy storage device; it can support the function of two LEDs for 20 minutes. These results indicate that the MCP-2//AC ASC will play an important role in energy structures in the future. PMID- 29786723 TI - A highly sensitive and fast graphene nanoribbon/CsPbBr3 quantum dot phototransistor with enhanced vertical metal oxide heterostructures. AB - Although recent breakthroughs in reported graphene-based phototransistors with embedded quantum dots (QDs) have definitely been astonishing, there are still some obstacles in their practical use with regard to their electrical and optical performances. We show that through optimization of the vertical graphene nanoribbon (GNR)/QD/IGZO heterostructure and the ultrahigh efficiency of CsPbBr3 QDs, it is possible to significantly increase the on/off ratio (>103), the subthreshold slope (S.S., 0.9 V dec-1), the device's field effect mobility (MUFET, 13 cm-1 V-1 S-1) and other electrical properties. Subsequently, on the basis of the extra optical-electrical characterization, we attribute the enhanced photosensitivity (800), the accelerated detecting speed (141 MUs) and the high detectivity (7.5 * 1014 cm Hz1/2 W-1) to the vertical heterostructure associated with the optimized GNR component. To further demonstrate this enhancement phenomenon, the mechanism and theory mode of this vertical heterostructure are analyzed and exploited in this letter. This research indicates that a highly sensitive and fast phototransistor can be realized using the novel GNR/QD/IGZO vertical heterostructure and the long diffusion length of the perovskite QD photosensing component. PMID- 29786724 TI - Influence of a nanoparticle on the structure and dynamics of model ionomer melts. AB - We simulate a single spherical nanoparticle (NP) surrounded by partially neutralized ionomers. The coarse-grained ionomers consist of a linear backbone of neutral monomer beads with charged pendant beads and counterions, along with pendant 'sticker' beads that represent unneutralized acid groups. Two different NP interactions are considered; one in which the NP interacts uniformly with all beads in the system (neutral NP) and another in which the NP has higher cohesive interactions with ions and stickers (sticky NP). Ions are depleted around the neutral NP relative to the bulk, but are denser around the surface of the sticky NP. The bond vector autocorrelation function was computed as a function of distance from the NP. For the neutral NP, due to the absence of ions, there is an increase in bond rotational dynamics near the surface relative to the bulk, while the reverse trend is observed in the case of the sticky NP. These analyses were done systematically for differing mole content of pendants, levels of neutralization, and NP sizes; lower pendant content causes a significantly larger difference in the bond dynamics near and far from the NP surface. PMID- 29786725 TI - A convergent strategy towards febrifugine and related compounds. AB - We report a modular five step synthetic route to the febrifugines that employs 2 (chloromethyl)allyl-trimethylsilane as a conjunctive reagent for the coupling of the piperidine and quinazolinone groups. We also demonstrate the application of a recent Rh-catalyzed quinazolinone synthesis for the facile generation of febrifugine analogs. PMID- 29786726 TI - Boron-doped graphene nanosheet-supported Pt: a highly active and selective catalyst for low temperature H2-SCR. AB - A series of boron-doped graphene-supported Pt (Pt/BG) nanosheets were designed and synthesized using a one-step facile hydrothermal method. ICP, XPS, and TPD results confirmed that boron atoms were successfully embedded into the graphene matrix. The selective catalytic reduction of nitric oxide with hydrogen (H2-SCR) was tested over Pt/BG catalysts. The multi-roles of doped-boron were investigated by Raman, BET, CO-chemisorption, H2-TPD, XPS, and NO-TPD. Boron doping led to a higher dispersion and smaller size of Pt nanoparticles, facilitated hydrogen spillover, promoted more metallic Pt formation, and increased both H2 and NO chemisorption, which were attributed to an enhanced Pt nucleation rate over doped boron, electron donation from boron to Pt, and extra chemisorption sites. The reaction performances (conversion 94.7%, selectivity 90.3%, and TOF 0.092 s-1) were greatly promoted attributing to a bifunctional catalytic mechanism. This work paves the way to modify the structure and tune the chemisorption ability of graphene-based catalysts, and provides novel insights for designing high performance catalysts. PMID- 29786727 TI - Rational design of multi-functional gold nanoparticles with controlled biomolecule adsorption: a multi-method approach for in-depth characterization. AB - Multi-functionalized nanoparticles are of great interest in biotechnology and biomedicine, especially for diagnostic and therapeutic purposes. However, at the moment the characterization of complex, multi-functional nanoparticles is still challenging and this hampers the development of advanced nanomaterials for biological applications. In this work, we have designed a model system consisting of gold nanoparticles functionalized with two differentially-terminated poly(ethylene oxide) ligands, providing both "stealth" properties and protein binding capabilities to the nanoparticles. We use a combination of techniques (Centrifugal Liquid Sedimentation, Dynamic Light Scattering, Flow Field Flow Fractionation, Transmission Electron Microscopy, and Circular Dichroism) to: (i) monitor and quantify the ratios of ligand molecules per nanoparticle; (ii) determine the effect of coating density on non-specific protein adsorption; (iii) to assess the number and structure of the covalently-bound proteins. This article aims at comparing the complementary outcomes from typical and orthogonal techniques used in nanoparticle characterization by employing a versatile nanoparticle-ligands-biomolecule model system. PMID- 29786728 TI - Selenization of NiMn-layered double hydroxide with enhanced electrocatalytic activity for oxygen evolution. AB - Exploiting highly active oxygen evolution reaction electrocatalysts is of great importance in the cost-effective generation of clean fuels. Herein, the preparation of NiMn-layered double hydroxide with selenization is adopted to reduce the charge transfer resistance of the electrocatalytic oxygen evolution reaction and enhance electrocatalytic performance. As a result, this selenization product of NiMn-layered double hydroxide can reach a current density of 10 mA cm 2 at a low overpotential of 280 mV on glassy carbon electrode in 1.0 M KOH aqueous solution and have excellent stability, which makes them comparable to the most efficient IrO2 catalyst and better than most nickel based catalysts. PMID- 29786729 TI - Application of a constant hole volume Sanchez-Lacombe equation of state to mixtures relevant to polymeric foaming. AB - A variant of the Sanchez-Lacombe equation of state is applied to several polymers, blowing agents, and saturated mixtures of interest to the polymer foaming industry. These are low-density polyethylene-carbon dioxide and polylactide-carbon dioxide saturated mixtures as well as polystyrene-carbon dioxide-dimethyl ether and polystyrene-carbon dioxide-nitrogen ternary saturated mixtures. Good agreement is achieved between theoretically predicted and experimentally determined solubilities, both for binary and ternary mixtures. Acceptable agreement with swelling ratios is found with no free parameters. Up-to date pure component Sanchez-Lacombe characteristic parameters are provided for carbon dioxide, dimethyl ether, low-density polyethylene, nitrogen, polylactide, linear and branched polypropylene, and polystyrene. Pure fluid low-density polyethylene and nitrogen parameters exhibit more moderate success while still providing acceptable quantitative estimations. Mixture estimations are found to have more moderate success where pure components are not as well represented. The Sanchez-Lacombe equation of state is found to correctly predict the anomalous reversal of solubility temperature dependence for low critical point fluids through the observation of this behaviour in polystyrene nitrogen mixtures. PMID- 29786730 TI - Dimensional control of supramolecular assemblies of diacetylene-derived peptide gemini amphiphile: from spherical micelles to foamlike networks. AB - Peptide amphiphiles capable of assembling into multidimensional nanostructures have attracted much attention over the past decade due to their potential applications in materials science. Herein, a novel diacetylene-derived peptide gemini amphiphile with a fluorenylmethyloxycarbonyl (Fmoc) group at the N terminus is reported to hierarchically assemble into spherical micelles, one dimensional nanorods, two-dimensional foamlike networks and lamellae. Solvent polarity shows a remarkable effect on the self-assembled structures by changing the balance of four weak noncovalent interactions (hydrogen-bonding, pi-pi stacking, hydrophobic interaction, and electrostatic repulsion). We also show the time-evolution not only from spherical micelles to helical nanofibers in aqueous solution, but also from branched wormlike micelles to foamlike networks in methanol solution. In this work, the presence of the Fmoc group plays a key role in the self-assembly process. This work provides an efficient strategy for precise morphological control, aiding the future development in materials science. PMID- 29786731 TI - Regioselective and diastereoselective synthesis of two functionalized 1,5 methanoindeno[1,2-d]azocines via a three-component reaction. AB - The morpholine promoted three-component reaction of N-alkylpiperidinone, indane 1,3-dione and 2-arylideneindane-1,3-dione in ethanol at room temperature resulted in the (1H-1,5-methanoindeno[1,2-d]azocin-12-ylidene)-1H-indene-1,3(2H)-dione derivatives in good yields and with exo-configuration. Under similar conditions, the reaction of N-alkylpiperidinone with 2-arylideneindane-1,3-dione afforded 7H 1,5-methanoindeno[1,2-d]azocine-7,12-diones with endo-configuration. The domino reaction is believed to proceed with domino Knoevenagel condensation, Michael addition and aldol condensation reaction. PMID- 29786732 TI - Unusually low thermal conductivity of atomically thin 2D tellurium. AB - Tellurium is a high-performance thermoelectric material due to its superior electronic transport and low lattice thermal conductivity (kappaL). Here, we report the ultralow kappaL in the monolayer tellurium, i.e., tellurene, which has been successfully synthesized in recent experiments. We find that tellurene has a compellingly low room temperature kappaL of 2.16 and 4.08 W m-1 K-1 along the armchair and zigzag directions, respectively, which is lower than any reported values for other 2D materials. We attribute this unusually low kappaL to the soft acoustic modes, the extremely low-energy optical modes and the strong scattering among optical-acoustic phonons, which place tellurene as a potential novel thermoelectric material. Finally, we show that kappaL is proportional to the largest acoustic phonon frequency (omegaaD) and the lowest optical phonon frequency at the Gamma point (omegaoGamma) in 2D materials, which reflect both harmonic and anharmonic thermal properties, respectively. PMID- 29786733 TI - A facet-controlled Rh3Pb2S2 nanocage as an efficient and robust electrocatalyst toward the hydrogen evolution reaction. AB - Highly active and durable electrocatalysts for the hydrogen evolution reaction (HER) may play a pivotal role in commercial success of electrolytic water splitting technology. Among various material classes, binary metal sulphides show a great promise as HER catalysts because of their tunable energy levels conducive to a high catalytic activity and high robustness under harsh operating conditions. On the other hand, facet-controlled nanoparticles with controlled surface energies have gained great recent popularity as active and selective catalysts. However, binary metal sulphide nanoparticles with well-defined facets and high surface areas are very rare. Herein we report the synthesis of a facet controlled hollow Rh3Pb2S2 nanocage as a new catalytic material and its excellent activity (overpotential: 87.3 mV at 10 mA cm-2) and robustness toward HER under harsh acidic conditions. PMID- 29786734 TI - Preparation and characterisation of heterobimetallic copper-tungsten hydride complexes. AB - The preparation and structural characterisation of three new heterobimetallic hydride complexes containing 3-centre,2-electron W-H-Cu bonds is reported. These complexes have been characterised by single crystal X-ray crystallography and multinuclear NMR spectroscopy. The bonding in these complexes has been analysed by DFT calculations. PMID- 29786736 TI - Phase behaviour and applications of a binary liquid mixture of methanol and a thermotropic liquid crystal. AB - Herein, we report on the phase behaviour of a binary liquid mixture composed of methanol (MeOH) and the thermotropic liquid crystal 4-cyano-4'-pentylbiphenyl (5CB). The corresponding phase diagram combines features of a conventional liquid liquid mixture with characteristics that are particular to the nematic liquid crystal. We observe four arrangements as a function of composition and temperature, namely monophasic isotropic, monophasic nematic, biphasic isotropic isotropic and biphasic isotropic-nematic, with an upper critical solution temperature of 24.4 +/- 0.5 degrees C. The interplay of nematogenic and non nematogenic species offers tunability of phase mixing and phase composition in an accessible temperature window and provides novel routes for the extraction of target compounds, here exemplarily shown for Crystal Violet, Doxorubicin, Eosin Y, Rhodamine 6G and Sudan IV. PMID- 29786735 TI - Solvent-induced ion separation of a beryllium scorpionate complex. AB - Spontaneous ion separation of the scorpionate beryllium complex, TpBeI 1 (Tp = 1 trispyrazolylborate), occurs upon treatment with THF, yielding [TpBe(thf)]I 2, which was characterized by heteronuclear NMR spectroscopy (1H, 9Be, 13C) and structurally characterized by single crystal X-ray diffraction. 2 represents a rare example of a structurally characterized monocationic beryllium complex, and to the best of our knowledge, the synthesis of 2 by a solvent-induced ion separation has previously only been observed in the reactions of beryllium dihalides with strong Lewis bases. PMID- 29786737 TI - Anti-amyloidogenic properties of an ethyl acetate fraction from Actinidia arguta in Abeta1-42-induced ICR mice. AB - This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Abeta)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Abeta-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Abeta-induced neuroblastoma MC-IXC cells. The administration of EFAA significantly attenuated Abeta-induced learning and memory deficits, which were evaluated by Y-maze, passive avoidance, and Morris water maze tests. Furthermore, EFAA showed the ameliorating effect of cholinergic functions by increasing acetylcholine (ACh) levels and decreasing acetylcholinesterase (AChE) activity, and protected antioxidant systems by increasing superoxide dismutase (SOD) and decreasing the oxidized glutathione (GSH)/total GSH and malondialdehyde (MDA) in the brain. Finally, EFAA prevented mitochondrial dysfunction via regulating apoptotic signaling molecules including phosphorylated Akt (p-Akt), phosphorylated tau (p tau), Bax, and cytochrome c in the brain tissues. Therefore, the present study suggests that EFAA might be a potential source of natural antioxidants with the ability to ameliorate Abeta-induced amnesia. PMID- 29786738 TI - Design and mechanistic study of a novel gold nanocluster-based drug delivery system. AB - Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging. PMID- 29786739 TI - Synthesis of pure silica MFI zeolites using imidazolium-based long dications. A comparative study of structure-directing effects derived from a further spacer length increase. AB - Length-dependent structure direction of linear methylimidazolium-based dications towards MFI zeolite, previously known only for the tetramethylene spacer, has also been found for octamethylene and decamethylene spacers. This works only under highly concentrated conditions, whereas dilution always tends to favor TON, a default structure that is the only zeolite obtained with the other reported dications (with tri-, penta-, and hexamethylene spacers). The locations and conformations of the dications have been studied by molecular mechanics simulations. As longer dications introduce lower density of positive charges in the zeolite, the density of connectivity defects also decreases. Finally, these long dications cannot easily place each charged imidazolium ring in the two possible orientations (either parallel or perpendicular to 4MR close to F- sites) found for the tetramethylene case. Hence, although the three MFI materials display two 19F NMR resonances at similar chemical shifts, their relative intensities strongly vary as a function of the spacer length. PMID- 29786740 TI - Shear-density coupling for a compressible single-component yield-stress fluid. AB - Flow behavior of a single-component yield stress fluid is addressed on the hydrodynamic level. A basic ingredient of the model is a coupling between fluctuations of density and velocity gradient via a Herschel-Bulkley-type constitutive model. Focusing on the limit of low shear rates and high densities, the model approximates well-but is not limited to-gently sheared hard sphere colloidal glasses, where solvent effects are negligible. A detailed analysis of the linearized hydrodynamic equations for fluctuations and the resulting cubic dispersion relation reveals the existence of a range of densities and shear rates with growing flow heterogeneity. In this regime, after an initial transient, the velocity and density fields monotonically reach a spatially inhomogeneous stationary profile, where regions of high shear rate and low density coexist with regions of low shear rate and high density. The steady state is thus maintained by a competition between shear-induced enhancement of density inhomogeneities and relaxation via overdamped sound waves. An analysis of the mechanical equilibrium condition provides a criterion for the existence of steady state solutions. The dynamical evolution of the system is discussed in detail for various boundary conditions, imposing either a constant velocity, shear rate, or stress at the walls. PMID- 29786741 TI - Halo-substituted benzenesulfonyls and benzenesulfinates: convenient sources of arenes in metal-catalyzed C-C bond formation reactions for the straightforward access to halo-substituted arenes. AB - Palladium-catalyzed reactions using aryl halides as one of the coupling partners represent a very popular method for generating carbon-carbon bonds. However, such couplings suffer from important limitations. As most palladium catalysts are very effective for the cleavage of C-halo bonds (Halo = Cl, Br or I), in many cases, the presence of several halide functional groups on arenes is not tolerated. Since two decades, and especially during the last few years, a new class of coupling partners, benzenesulfonyl and benzenesulfinate derivatives, has emerged as a powerful alternative to aryl halides for the Pd-catalyzed C-C bond formation, as the reactions performed with these substrates generally tolerate C halo bonds. With these substrates, after a metal-catalyzed desulfitative coupling, a variety of halo-substituted arenes such as biaryls, styrenes, phenylacetylenes, acetophenones, benzonitriles... has been synthesized with high chemoselectivities. The use of these aryl sources allowed the synthesis of molecules containing several halo-substituents including iodo-substituents in only a few steps and provides very simple access to a very wide variety of halo substituted arenes useful to materials chemists and also to biochemists. In this review, we will summarize the scope of the use of halo-substituted benzenesulfonyls and benzenesulfinates as coupling partners in metal-catalyzed C C bond formation. PMID- 29786742 TI - A novel alendronate functionalized nanoprobe for simple colorimetric detection of cancer-associated hypercalcemia. AB - The calcium (Ca2+) ion concentration in the blood serum is tightly regulated, and any abnormalities in the level of serum calcium ions are associated with many potentially dangerous diseases. Thus, monitoring of the Ca2+ ion concentration in the blood serum is of fundamental importance. Gold nanoparticle (GNP)-based colorimetric biosensors have enormous potential in clinical diagnostic applications due to their simplicity, versatility, and unique optical properties. In this study, we have developed an alendronate functionalized gold nanoparticle (GNP-ALD) system for the measurement of Ca2+ ion concentration in biological samples. The GNP-ALD system showed higher sensitivity towards the Ca2+ ion compared to adenosine diphosphate (ADP) or adenosine triphosphate (ATP). The strong interaction between the Ca2+ ion and ALD at the GNP/solution interface resulted in significant aggregation of the ALD conjugated GNPs, and induced a color change of the solution from red to blue, which could be visually observed with the naked eye. The interaction between the Ca2+ ion and GNP-ALD was characterized by UV-visible spectroscopy, transmission electron microscopy (TEM) imaging, and dynamic light scattering (DLS) analysis. Under the optimized conditions, the lower limit of Ca2+ ion detection using this method was found to be 25 MUM and a linear response range from 25 MUM to 300 MUM Ca2+ ions was obtained with excellent discrimination against other metal ions. The GNP-ALD nanoprobe could successfully determine the ionized Ca2+ concentration in various serum samples and the results were validated using a commercial calcium assay kit. Moreover, as a practical application, we demonstrated the utility of this nanoprobe for the detection of cancer-associated hypercalcemia in a mouse model. PMID- 29786743 TI - Role of TGF-beta1 expressed in bone marrow-derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model. AB - Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor beta1 (TGF-beta1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) expressing TGF-beta1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGF-beta1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGF-beta1-overexpressing BMSCs, compared with PBS-treated controls. In addition, the TGF-beta1-overexpressing BMSCs promoted new bone formation in the rabbit femoral defect model, and increased the expression of bone-related markers at week 2 and week 6. Therefore, the study demonstrated that BMSCs overexpressing TGF-beta1 may provide a novel therapeutic option for femoral defects. PMID- 29786744 TI - miR-133b regulates proliferation and apoptosis in high-glucose-induced human retinal endothelial cells by targeting ras homolog family member A. AB - The aim of the present study was to investigate the role of microRNA (miR)-133b in high-glucose-induced human retinal endothelial cells (hRECs), particularly regarding its potential targeting of ras homolog family member A (RhoA). To establish the high-glucose-induced diabetic retinopathy (DR) model, hRECs were cultured in high-glucose medium for 1, 2 and 3 days. An Annexin allophycocyanin (APC)/7-aminoactinomycin D (7-AAD) staining assay was performed to measure the apoptosis of hRECs. Next, the cells were transfected with miR-133b inhibitors or mimics, and the cell proliferation and apoptosis were measured by MTT and Annexin APC/7-AAD staining assays, respectively. In addition, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunocytochemistry were used to detect the expression levels of RhoA, Rho associated protein kinase 1 (ROCK1), LIM domain kinase 1 (LIMK), myosin light chain (MLC) and phosphorylated (p)-MLC. It was observed that high-glucose or miR 133b inhibitor treatment attenuated the apoptosis of hRECs, and upregulated the mRNA and protein expression levels of RhoA, ROCK1 and LIMK, as well as the p-MLC protein level, in the hRECs. However, miR-133b overexpression inhibited the cell proliferation, promoted apoptosis, and downregulated the mRNA and protein levels of RhoA, ROCK1 and LIMK, as well as p-MLC protein, in high-glucose-induced hRECs. In conclusion, overexpression of miR-133b inhibited the proliferation and promoted apoptosis in a DR cell model by downregulating RhoA expression. PMID- 29786746 TI - Luteolin induces myelodysplastic syndrome-derived cell apoptosis via the p53 dependent mitochondrial signaling pathway mediated by reactive oxygen species. AB - Luteolin, a common dietary flavonoid, induces the apoptosis of cells in several types of cancer. However, its role in myelodysplastic syndrome (MDS) and the potential underlying mechanisms remain to be elucidated. To evaluate the potential benefit and underlying mechanisms of luteolin in MDS cells, the viability of SKM-1 cells and primary bone marrow (PBM) mononuclear cells from patients with intermediate- or high-risk MDS were assessed using a Cell Counting Kit-8 assay. The apoptotic features of cell morphology were assessed using Wright Giemsa staining, DNA fragmentation was analyzed by agarose gel electrophoresis, and the extent of apoptosis was quantified by flow cytometry (FCM). Reactive oxygen species (ROS) were measured by FCM with 2,7-dichlorodihydrofluorescein diacetate staining and mitochondrial membrane potential (DeltaPsim) was determined using 5,5',6,6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide staining. Caspase activity was detected using a fluorometric protease assay. Furthermore, the effects of luteolin on the expression of apoptosis-related proteins were analyzed using western blot analysis. The resulting data revealed that luteolin significantly inhibited the proliferation of SKM-1 cells in vitro, and its half maximal inhibitory concentration was 139.41 uM at 24 h and 23.95 uM at 72 h. Luteolin also markedly inhibited the proliferation of mononuclear cells from patients with intermediate- or high-risk MDS. Luteolin suppressed cell proliferation, mainly as a result of the induction of apoptosis, as demonstrated by typical apoptotic morphological features, the ladder pattern of genomic DNA fragmentation, and the results of FCM using Annexin V-FITC/PI double staining. It was also found that short-term exposure of SKM-1 cells to luteolin led to a marked increase in the accumulation of ROS. The increased intracellular level of ROS appeared to induce the activation of p53 and elevate the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio, which modulates DeltaPsim and triggers the release of cytochrome c, and may increase the activities of apoptotic protease activating factor 1, caspase-3, -8 and -9 to further trigger the destruction of structural and specific proteins and thereby cell apoptosis. Notably, the inhibition of ROS generation by the antioxidant N-acetyl-L-cysteine significantly attenuated the luteolin-induced loss of DeltaPsim and activities of caspase-3, -8 and -9. These data suggested that luteolin exerts its pro-apoptotic action partly through the p53-dependent mitochondrial signaling pathway mediated by intracellular ROS, which provides a promising therapeutic candidate for patients with MDS. PMID- 29786747 TI - MicroRNA-137 dysregulation predisposes to osteoporotic fracture by impeding ALP activity and expression via suppression of leucine-rich repeat-containing G protein-coupled receptor 4 expression. AB - Osteoporosis is defined as a loss of bone mass and deterioration of its architecture resulting in bone weakness, which becomes prone to fracture. The objective of this study was to investigate the molecular mechanism by which miR 137 can reduce the risk of fracture in patients with osteoporosis. An online miRNA database and a luciferase reporter assay system were used to confirm that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) was the target of miR-137. Real-time PCR and western blot analysis were used to study miR-137 mRNA, the expression of LGR4 mRNA and protein among different groups or cells transfected with a scrambled miRNA control, miR-137 mimic, LGR4 siRNA and miR-137 inhibitor. Expression of miR-137 was upregulated to higher levels in cells isolated from osteoporosis patients with fracture than in those without fracture. The 'seed sequence' was found to be located within the 3' untranslated region (3' UTR) of LGR4 mRNA by searching an online miRNA database. Luciferase reporter assay was performed to confirm that LGR4 is a direct target gene of miR-137 with a potential binding site in the 3'UTR of LGR4. Luciferase activity of cells transfected with wild-type LGR4 3'UTR was much lower than that of the cells transfected with mutant LGR4 3'UTR. The results of real-time PCR and immunohistochemistry experiments demonstrated that the expression levels of LGR4 mRNA and protein were much higher in osteoporosis patients with fracture than osteoporosis patients without fracture. We found that the expression levels of LGR4 mRNA and protein were clearly upregulated following transfection with miR 137 inhibitor, while noticeably downregulated following transfection with miR-137 mimic when compared with the scramble control. Furthermore, the expression of ALP mRNA and ALP activity in bone tissue were much higher in osteoporosis patients with fracture than those without fracture. In conclusion, these data prove that the overexpression of miR-137 was associated with an altered risk of fracture in patients with osteoporosis, and can be used as a biomarker for the prediction of risk of fracture in osteoporosis. PMID- 29786745 TI - Histone modifications in fatty acid synthase modulated by carbohydrate responsive element binding protein are associated with non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and is closely associated with diabetes; however, its pathogenesis remains to be elucidated. Carbohydrate responsive element binding protein (ChREBP), the hub of glucolipid metabolism, regulates the induction of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, by directly binding to carbohydrate response element (ChoRE) in its promoter. Investigations of histone modifications on NAFLD remain in their infancy. In the present study, by using ChIP, the association between histone modifications and FASN transcription was investigated and histone modifications in FASN modulated by ChREBP were measured. It was demonstrated that ChREBP induced FASN ChREBP-ChoRE binding to accelerate the expression of FASN, leading to hepatocellular steatosis by facilitating H3 and H4 acetylation, H3K4 trimethylation and the phosphorylation of H3S10, but inhibiting the trimethylation of H3K9 and H4K20 in FASN promoter regions of HepG2 and L02 cells. It was also found that ChREBP-ChoRE binding of FASN relied on histone acetylation and that the transcriptional activity of ChREBP on FASN is required, based on the premise that histone acetylation causes conformational changes in FASN chromatin. This indicated histone acetylation as a crucial mechanism involved in the transcription of FASN modulated by ChREBP. Consequently, the present study provides further insight into the pathophysiology and a novel therapeutic potential of NAFLD based on epigenetic mechanisms. PMID- 29786748 TI - Protective effects of dehydrocostuslactone on rat hippocampal slice injury induced by oxygen-glucose deprivation/reoxygenation. AB - The present study aimed to investigate the protective effects of dehydrocostuslactone (DHL) against rat hippocampal slice injury caused by oxygen glucose deprivation/reoxygenation (OGD/R). Rat hippocampal slice injury was induced by OGD/R in vitro, and the degree of injury was evaluated through a lactate dehydrogenase (LDH) assay and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (cyt-c), apoptotic protease activating factor 1 (apaf-1), caspase-9, caspase-7, caspase-3, sequestosome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3 (LC3) were analyzed through western blot analysis. The results showed that 1, 5 and 10 uM DHL decreased the levels of LDH (P<0.05) and increased the A490 value of TTC (P<0.05). Furthermore, the expression of Bcl-2 was enhanced, and the protein expression levels of Bax, cyt-c, apaf-1, caspase-9, caspase-7, caspase-3, SQSTM1 and LC3 were significantly inhibited (P<0.05), compared with those in the OGD/R group. These results suggested that DHL elicited protective effects against hippocampal OGD/R injury, and its underlying mechanism may be associated with inhibiting apoptosis. PMID- 29786749 TI - Long noncoding RNA myocardial infarction-associated transcript is associated with the microRNA-150-5p/P300 pathway in cardiac hypertrophy. AB - In numerous diseases, abnormal expression of myocardial infarction-associated transcript (MIAT) has been reported to be involved in cell proliferation, apoptosis and migration. However, whether this long non-coding RNA MIAT has a regulatory effect on heart hypertrophy requires further investigation. To this end, the present study evaluated MIAT in hypertrophic cardiomyocytes in vitro and in vivo. Neonatal rat ventricular myocytes (NRVMs) were induced by isoproterenol (ISO) to create a cell hypertrophy model, and mice were intraperitoneally injected with ISO to establish an animal model. Echocardiography, immunofluorescence staining, western blot analysis, RNA isolation and reverse transcription-polymerase chain reaction were applied to test the involvement of MIAT in cardiac hypertrophy. The results revealed that MIAT was upregulated under ISO stimulation at the mRNA level both in vivo and in vitro. Silencing of MIAT resulted in decreased expression levels of atrial natriuretic peptide and brain natriuretic peptide in ISO-treated NRVM cardiomyocytes, confirming the connection between MIAT and hypertrophy. Furthermore, MIAT small interfering RNA significantly increased microRNA (miR)-150 and decreased P300 expression in NRVMs. In conclusion, the MIAT/miR-150-5p axis targets P300 as a positive regulator of cardiomyocyte hypertrophy. PMID- 29786750 TI - MicroRNA-20b-5p promotes ventricular remodeling by targeting the TGF-beta/Smad signaling pathway in a rat model of ischemia-reperfusion injury. AB - Myocardial ischemic injury results from severe impairment of the coronary blood supply and may lead to metabolic and ultrastructural changes, thereby causing irreversible damage. MicroRNA (miR)-20b-5p has been demonstrated to be involved in malignancies of the breast, colorectum, stomach, blood and oropharynx. The present study aimed to investigate the effects of miR-20b-5p on ventricular remodeling following myocardial ischemia-reperfusion (IR) injury in rats by targeting small mothers against decapentaplegic homolog 7 (Smad7) via the transforming growth factor-beta (TGF-beta)/Smad signaling pathway. A total of 70 adult male Sprague-Dawley rats were divided into seven groups: Sham group, IR group, negative control group, miR-20b-5p mimics group, miR-20b-5p inhibitors group, small interfering RNA (siRNA)-Smad7 group, and miR-20b-5p inhibitors + siRNA-Smad7 group. Dual luciferase reporter gene assays were used to verify the association between miR-20b-5p and Smad7. Myocardial infarction size, myocardial collagen volume fraction and perivascular collagen area were detected separately using triphenyltetrazolium chloride and Masson's staining. The rate of positive expression of Smad7 was detected using immunohistochemistry, and the expression levels of miR-20b-5p, TGF-beta1, Smad3 and Smad7 were detected using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The findings revealed that miR-20b-5p inhibited Smad7. Compared with the sham group, the other six groups had increased myocardial infarction size, myocardial collagen, and expression of miR-20b-5p, TGF-beta1 and Smad3, and decreased expression of Smad7. Compared with the IR group, the miR-20b-5p mimics group and the siRNA-Smad7 group had increased myocardial infarction size and myocardial collagen, increased expression of TGF-beta1 and Smad3, and decreased expression of Smad7. The expression of miR-20b-5p was markedly increased in the miR-20b-5p mimics group, but did not differ significantly from that in the siRNA-Smad7 group. The results demonstrated that miR-20b-5p promoted ventricular remodeling following myocardial IR injury in rats by inhibiting the expression of Smad7 through activating the TGF-beta/Smad signaling pathway. PMID- 29786751 TI - Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin. AB - Periprosthetic osteolysis belongs to osteolytic diseases, which often occur due to an imbalance between osteoclast and osteoblast number or activity. Fraxetin, a natural plant extract, inhibits osteoblast apoptosis and has therapeutic potential for treating osteolytic diseases. However, data pertaining to the effects of fraxetin on osteoclasts are limited. In the present study, it was demonstrated that the inhibition of osteoclastogenesis by fraxetin had an important role on the therapy of titanium particle-induced osteolysis in vivo. In addition, fraxetin was demonstrated to suppress receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. Fraxetin inhibited osteoclast differentiation and function through the suppression of p38 signaling and subsequently, the suppression of osteoclast-specific gene expression, including tartrate-resistant acid phosphatase, nuclear factor of activated T-cells, cytoplasmic 1, and cathepsin K. In conclusion, fraxetin administration may have potential as a treatment method for periprosthetic osteolysis and other osteolytic diseases. PMID- 29786752 TI - Overexpression of miR-17-5p protects against high glucose-induced endothelial cell injury by targeting E2F1-mediated suppression of autophagy and promotion of apoptosis. AB - E2 promoter binding factor 1 (E2F1) has been reported to have an important regulatory role in cell survival during hyperglycemic conditions; however, the mechanisms remain to be fully elucidated. Bioinformatics analyses have suggested that microRNA (miR)-17-5p targets the 3'untranslated region (3'UTR) of E2F1. The aim of the present study was to characterize the protective effect of miR-17 5p/E2F1 on human umbilical vein endothelial cells (HUVECs) under high glucose (HG) conditions, to confirm the regulatory effect of miR-17-5p on E2F1/AMP activated protein kinase alpha2 (AMPKalpha2)-mediated apoptosis and E2F1/mammalian target of rapamycin complex 1 (mTORC1)-mediated autophagy. Bifluorescein experiments were performed to characterize the interaction between miR-17-5p and E2F1. The Cell Counting Kit-8 assay, flow cytometry, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect cell viability, apoptosis, autophagy, and relative mRNA and protein expression, respectively. The results showed that HG induced the downregulation of miR-17-5p and upregulation of E2F1 during HUVEC injury. The downregulation of E2F1 inhibited HG-induced HUVEC dysfunction by suppressing mTORC1-mediated inhibition of autophagy and AMPKalpha2 mediated promotion of apoptosis. The results suggested that inhibiting the expression of E2F1 protected against HG-induced HUVEC injury via the activation of autophagy. The overexpression of miR-17-5p inhibited E2F1-mediated HUVEC injury under HG conditions, which was reversed following transfection with an E2F1-overexpression vector. The bifluorescein experiments showed that miR-17-5p targeted the 3'UTR of E2F1. Taken together, the results suggested that the expression of miR-17-5p inhibited HG-induced endothelial cell injury by targeting E2F1. PMID- 29786753 TI - Hypoxia-induced expression of CXCR4 favors trophoblast cell migration and invasion via the activation of HIF-1alpha. AB - The placenta initially develops in a low-oxygen environment up to week 8-10 of gestation, and a low oxygen level is a critical factor in the regulation of trophoblast migration and invasion. CXC chemokine receptor 4 (CXCR4) is transcriptionally activated by hypoxia in cancer cells. However, whether CXCR4 is involved in hypoxia-inducible factor (HIF)-1alpha-dependent trophoblastic migration and invasion in a physiologically hypoxic environment (3% O2) remains to be fully elucidated and requires further investigation. In the present study, the expression of CXCR4 in first-trimester villi was investigated, as was the response of the trophoblast to hypoxia, and the role of CXCR4 and HIF-1alpha in trophoblast migration and invasion. CXCR4 was significantly elevated in the first trimester villi compared with normal full-term placentas. In vitro, the expression of CXCR4 at the mRNA and protein levels was increased in JEG3 cells exposed to 3% O2 in a time-dependent manner, and the migratory and invasive abilities of the JEG3 cells were upregulated. In addition, CXCR4 knockdown by transfection with CXCR4-specific small interfering (si)RNA decreased the migration and invasion of JEG3 cells exposed to 3% O2. Furthermore, synthetic siRNA specific for HIF-1alpha significantly suppressed the expression of CXCR4 in JEG3 cells exposed to 3% O2, whereas pcDNA-HIF-1alpha significantly increased the expression of CXCR4. These results indicated that the hypoxia-induced expression of CXCR4 promoted trophoblast cell migration and invasion via the activation of HIF-1alpha, which is crucial during placentation. PMID- 29786754 TI - Regulation of interferon signaling and HCV-RNA replication by extracellular matrix. AB - Although interferon (IFN)-based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH-7 human hepatoma cell line and HuH-7 cells were stably transfected with full-length HCV-RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM-coated dishes or non-coated plastic dishes (NDs), and treated with human IFN-alpha. In Huh-7 cells cultured on coated dishes, the IFN-stimulated response element (ISRE) luciferase activity was measured following ISRE plasmid transfection and the expression of IFN-stimulated genes (ISG) were significantly lower than those in cells cultured on NDs. In addition, after IFN-alpha treatment, the amount of HCV-RNA and viral protein produced by OR6 cells cultured on coated dishes was higher than that produced by cells cultured on NDs. When cells were treated with beta1-integrin-blocking antibody to disrupt the cell matrix interaction, the ISRE luciferase activity was restored, and the protein expression of ISG was increased, while that of HCV proteins was suppressed. Treatment of cells with integrin-linked kinase (ILK) inhibitor or focal adhesion kinase (FAK) inhibitor restored the ISRE luciferase activity and expression of ISG proteins. These results suggested that beta1-integrin-mediated signals affected the IFN signaling and promoted HCV replication. Therefore, the accumulation of ECM in liver fibrosis may impair IFN signaling through beta1 integrin-mediated signaling involving ILK and FAK. PMID- 29786755 TI - Cardiac progenitor cell-derived exosomes promote H9C2 cell growth via Akt/mTOR activation. AB - Exosomes are cell-derived vesicles released from a variety of mammalian cells that are involved in cell-to-cell signalling. It has been reported that cardiac progenitor cells (CPCs) derived from an adult heart are one of the most promising stem cell types for cardioprotection and repair. The mammalian target of rapamycin (mTOR) signalling pathway is a pivotal regulator in CPCs, therefore, CPC-derived exosomes were used in the present study to investigate whether it can promote H9C2 cell growth through the protein kinase B (PKB, or Akt)/mTOR signalling pathway. The CPCs were isolated from Sprague-Dawley hearts. Following treatment with a specific medium, the exosomes were purified and identified by electron micrograph and western blot assays, using CD63 and CD81 as markers. The methyl-thiazolyl-tetrazolium and 5-ethynyl-2'-deoxyuridine methods were used to detect H9C2 cell growth. The expression of Akt and mTOR were detected by western blot analysis following treatment with 200 or 400 ug/ml of exosomes for 24 or 48 h, respectively. It was found that, compared with higher concentrations of exosomes, prolonging the duration of exposure promoted cell growth. Accordingly, CPC-derived exosomes stimulated the expression of Akt to a marked degree; groups treated with exosomes for 48 h showed higher expression of Akt than those treated for 24 h at the same concentration. mTOR was also stimulated by CPC-derived exosomes. The activation of mTOR increased in accordance with the treatment time at an exosome concentration of 200 ug/ml and decreased with treatment time at an exosome concentration of 400 ug/ml. In conclusion, the present study demonstrated that CPC-derived exosomes promoted H9C2 cell growth via the activation of Akt/mTOR in a time-dependent manner at a relatively low exosome concentration, which may provide a novel therapy for cardiovascular disease. PMID- 29786756 TI - Backbone NMR assignments of HypF-N under conditions generating toxic and non toxic oligomers. AB - The HypF protein is involved in the maturation and regulation of hydrogenases. The N-terminal domain of HypF (HypF-N) has served as a key model system to study the pathways of protein amyloid formation and the nature of the toxicity of pre fibrilar protein oligomers. This domain can aggregate into two forms of oligomers having significantly different toxic effects when added to neuronal cultures. Here, NMR assignments of HypF-N backbone resonances are presented in its native state and under the conditions favouring the formation of toxic and non-toxic oligomers. The analyses of chemical shifts provide insights into the protein conformational state and the possible pathways leading to the formation of different types of oligomers. PMID- 29786759 TI - A Novel MYCN Variant Associated with Intellectual Disability Regulates Neuronal Development. PMID- 29786757 TI - Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes. AB - In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph- B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines. These findings suggest that CNAs are correlated with genetic subtype in B-ALL cell lines. In addition, we determined that three B-other ALL cell lines had IKZF1 deletions (YCUB-5, KOPN49, and KOPN75); we therefore performed comprehensive genetic analysis of these cell lines. YCUB-5, KOPN49, and KOPN75 had P2RY8-CRLF2, IgH-CRLF2, and PAX5-ETV6 fusions, respectively. Moreover, targeted capture sequencing revealed that YCUB-5 had JAK2 R683I and KRAS G12D, and KOPN49 had JAK2 R683G and KRAS G13D mutations. These data may contribute to progress in the field of leukemia research. PMID- 29786758 TI - Long-term complete remission following tandem autologous stem cell transplantation and consolidative radiotherapy for refractory mediastinal gray zone lymphoma. AB - Mediastinal gray zone lymphoma (MGZL) is a provisional entity with intermediate features between classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma. Outcomes for patients with MGZL are reportedly poorer than those for patients with cHL or primary mediastinal large B-cell lymphoma. Additionally, no standard management guidelines for patients with MGZL are available, primarily due to its recent identification, rarity, and challenges in diagnosis. Although recent several studies have suggested dose-adjusted EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisolone, and rituximab) may improve outcomes in patients with MGZL, numerous patients still suffer from relapsed/refractory MGZL, and the optimal management for such patients remains uncertain. Here, we report the first case of successful treatment of refractory MGZL by tandem high-dose chemotherapy supported by autologous stem cell transplantations (auto-SCTs) and consolidative radiotherapy (RT). To date, the patient remains in CR 33 months after the completion of RT, with no significant complications. This case suggests that tandem auto-SCTs may be a promising therapeutic option for relapsed/refractory MGZL. PMID- 29786760 TI - SIRT1 rs3758391 and Major Depressive Disorder: New Data and Meta-Analysis. PMID- 29786762 TI - Chronic conditions and multimorbidity in a primary care population: a study in the Swiss Sentinel Surveillance Network (Sentinella). AB - OBJECTIVES: To provide estimates of the prevalence of chronic conditions in Swiss primary care. METHODS: In total, 175 general practitioners (GP) or pediatricians (PED) reporting to the Swiss Sentinel Surveillance Network collected morbidity data. RESULTS: In 26,853 patient contacts, mean (+/- SD) age was 55.8 +/- 21.6 or 6.1 +/- 5.7 years (in GPs vs. PEDs, respectively) and 47% were males. In GP patients, median Thurgau Morbidity Index was 2 (IQR 1-3). The median numbers of chronic conditions and permanently used prescribed drugs were 2 (0-5) and 2 (1 4), respectively; in PEDs medians were 0. Out of all patients, 16.7 and 7.0% of the PED patients were hospitalized during the previous year; patients cared by family/proxies or community nurses were hospitalized significantly more often than patients living in homes (50.1 vs. 35.4%, OR 1.41, p < 0.001). Out of patients over 80 years of age, 51.5% were care dependent and 45.5% of the patients over 90 years were living in homes for the elderly. CONCLUSIONS: In a representative sample of Swiss primary care patients, a substantial part shows multimorbidity with a high prevalence of chronic diseases, multiple drug treatment, and care dependency. These data may serve to be compared with other patient groups or other primary care systems. Trial registration www.clinicaltrials.gov NCT0229537, national study registry www.kofam.ch SNCTP000001207. PMID- 29786761 TI - Engineering terpenoid production through transient expression in Nicotiana benthamiana. AB - Terpenoids are the most structurally diverse class of plant natural products with a huge range of commercial and medical applications. Exploiting this enormous potential has historically been hindered due to low levels of these compounds in their natural sources, making isolation difficult, while their structural complexity frequently makes synthetic chemistry approaches uneconomical. Engineering terpenoid biosynthesis in heterologous host production platforms provides a means to overcome these obstacles. In particular, plant-based production systems are attractive as they provide the compartmentalisation and cofactors necessary for the transfer of functional pathways from other plants. Nicotiana benthamiana, a wild relative of tobacco, has become increasingly popular as a heterologous expression platform for reconstituting plant natural product pathways, because it is amenable to Agrobacterium-mediated transient expression, a scalable and highly flexible process that enables rapid expression of genes and enzymes from other plant species. Here, we review recent work describing terpene production in N. benthamiana. We examine various strategies taken to engineer this host for increased production of the target metabolite. We also look at how transient expression can be utilised for rapid generation of molecular diversity, including new-to-nature products. Finally, we highlight current issues surrounding this expression platform and discuss the future directions and developments which will be needed to fully realise the potential of this system. PMID- 29786763 TI - miR-124 promotes proliferation and neural differentiation of neural stem cells through targeting DACT1 and activating Wnt/beta-catenin pathways. AB - Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, beta-tubulin III, glial fibrillary acidic protein (GFAP), beta-catenin, cyclinD1, and glycogen synthase kinase-3beta (GSK 3beta) were examined by qRT-PCR or western blot. Bioinformatics and Dual Luciferase reporter assay were used to identify the interaction between miR-124 and DACT1. MTS analysis was performed to measure the viability of NSCs. Enhanced expression of miR-124 and lowered expression of DACT1 were observed during a 14 day NSC differentiation period. DACT1 was verified as a direct target of miR-124. Moreover, overexpression of miR-124 promoted NSC proliferation and induced neuron specific differentiation, presented as increased cell viability, higher neurosphere number, elevated ki-67, Nestin, beta-tubulin III expressions, and decreased GFAP expression. Similarly, DACT1 downregulation facilitated proliferation and neuronal differentiation of NSCs. Furthermore, DACT1 overexpression impaired miR-124-induced proliferation and differentiation of NSCs. Additionally, miR-124 stimulated Wnt/beta-catenin signaling via suppressing DACT1 expression. miR-124 promoted proliferation and induced NSC differentiation to neurons by activation of Wnt/beta-catenin pathway via targeting DACT1, providing a potential target and aiding the development of cell-based therapies for neurological disorders. PMID- 29786764 TI - Encapsulation of micronutrients resveratrol, genistein, and curcumin by folic acid-PAMAM nanoparticles. AB - It has been shown that encapsulation of dietary polyphenols leads to increased solubility and bioavailability of these micronutrients. The encapsulation of dietary polyphenols resveratrol, genistein, and curcumin by folic acid-PAMAM-G3 and folic acid-PAMAM-G4 nanoparticles was studied in aqueous solution at physiological conditions, using multiple spectroscopic methods, TEM images, and docking studies. The polyphenol bindings are via hydrophilic, hydrophobic, and H bonding contacts with resveratrol forming more stable conjugates. As folic acid PAMAM nanoparticle size increased, the loading efficacy and the stability of polyphenol-polymer conjugates were increased. Polyphenol encapsulation induced major alterations of dendrimer morphology. Folic acid-PAMAM nanoconjugates are capable of delivery of polyphenols in vitro. PMID- 29786765 TI - Analysis of Streptomyces ghanaensis ATCC14672 gene SSFG_07725 for putative gamma butyrolactone synthase. AB - Low molecular weight signaling compounds (LMWC) are important players in regulating various aspects of Streptomyces biology. Their exact roles in certain strain will ultimately depend on overall configuration of regulatory network and thus cannot be predicted on basis of in silico studies. Here, we explored S. ghanaensis gene SSFG_07725 (afsAgh) presumably involved in initial steps of formation of gamma-butyrolactone LMWC. Disruption of afsAgh impaired aerial mycelium formation and increased the transcription of pleiotropic regulatory gene adpAgh, whereas level of moenomycin production remained virtually unaffected. We provide evidence that morphogenetic deficiency of afsAgh-minus mutant was caused by inability to produce diffusible LMWC. Possible links between gamma butyrolactone signaling and various aspects of S. ghanaensis biology are discussed. PMID- 29786766 TI - Bacterial DNA detected on pathologically changed heart valves using 16S rRNA gene amplification. AB - Nowadays, dental diseases are one of the most common illnesses in the world. Some of them can lead to translocation of oral bacteria to the bloodstream causing intermittent bacteraemia. Therefore, a potential association between oral infection and cardiovascular diseases has been discussed in recent years as a result of adhesion of oral microbes to the heart valves. The aim of this study was to detect oral bacteria on pathologically changed heart valves not caused by infective endocarditis. In the study, patients with pathologically changed heart valves were involved. Samples of heart valves removed during heart valve replacement surgery were cut into two parts. One aliquot was cultivated aerobically and anaerobically. Bacterial DNA was extracted using Ultra-Deep Microbiome Prep (Molzym GmbH, Bremen, Germany) followed by a 16S rRNA gene PCR amplification using Mastermix 16S Complete kit (Molzym GmbH, Bremen, Germany). Positive PCR products were sequenced and the sequences were analyzed using BLAST database ( http://www.ncbi.nlm.nih/BLAST ). During the study period, 41 samples were processed. Bacterial DNA of the following bacteria was detected in 21 samples: Cutibacterium acnes (formerly Propionibacterium acnes) (n = 11; 52.38% of patients with positive bacterial DNA detection), Staphylococcus sp. (n = 9; 42.86%), Streptococcus sp. (n = 1; 4.76%), Streptococcus sanguinis (n = 4; 19.05%), Streptococcus oralis (n = 1; 4.76%), Carnobacterium sp. (n = 1; 4.76%), Bacillus sp. (n = 2; 9.52%), and Bergeyella sp. (n = 1; 4.76%). In nine samples, multiple bacteria were found. Our results showed significant appearance of bacteria on pathologically changed heart valves in patients with no symptoms of infective endocarditis. PMID- 29786767 TI - Oral supplementation of Lanthanum Zirconate nanoparticles moderately affected behavior but drastically disturbed leukocyte count, serum cholesterol levels and antioxidant parameters from vital organs of albino mice in a gender specific manner. AB - Lanthanum Zirconate nanoparticles (NPs) are used in blades of gas turbine engines to thermally insulate them and to protect them against hot and corrosive gas streams. However, the information regarding their biocompatibility is limited. The present study was aimed to report the effect of Lanthanum Zirconate NPs on selected aspects of behavior, serum biochemistry, complete blood count and antioxidant parameters from vital organs of albino mice in a gender specific manner. Albino mice, seven weeks old, were orally treated with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles for consecutive 22 days. Saline treated control groups were maintained in parallel. It was observed that rearing frequency was significantly decreased (P = 0.01) in NPs treated male mice. Complete blood count analysis indicated that NPs treated female mice had significantly reduced white blood cells (P = 0.05) and lymphocytes count (P = 0.03). NPs treated male had significantly reduced serum cholesterol levels (P = 0.05) than control group. It was observed that Superoxide dismutase concentrations in liver (P = 0.025) and kidney (P = 0.008), Malondialdehyde concentrations in liver (P = 0.044) of female and Malondialdehyde concentrations in kidney (P < 0.001) and brain (P < 0.001) and catalase concentrations in liver (P = 0.05) of NPs treated male mice were significantly higher than their respective control groups.. In conclusion, we are reporting that oral supplementation with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles can affect the behavior, leukocyte count, serum cholesterol and antioxidant metabolites from vital organs of albino mice in a gender specific manner. PMID- 29786769 TI - Do fatal infectious diseases eradicate host species? AB - In simple SI epidemic and endemic models, three classes of incidence functions are identified for their potential to be associated with host extinction: weakly upper density-dependent incidences are never associated with host extinction. Power incidences that depend on the number of susceptibles and infectives by powers strictly between 0 and 1 are associated with initial-constellation dependent host extinction for all parameter values. Homogeneous incidences, of which frequency-dependent incidence is a very particular case, and power incidences are associated with global host extinction for certain parameter constellations and with host survival for others. Laboratory infection experiments with salamander larvae are equally well fitted by power incidences and certain upper density-dependent incidences such as the negative binomial incidence and do not rule out homogeneous incidences such as an asymmetric frequency-dependent incidence either. PMID- 29786768 TI - Risk Prediction Score for HIV Infection: Development and Internal Validation with Cross-Sectional Data from Men Who Have Sex with Men in China. AB - Receptive anal intercourse, multiple partners, condomless sex, sexually transmitted infections (STIs), and drug/alcohol addiction are familiar factors that correlate with increased human immunodeficiency virus (HIV) risk among men who have sex with men (MSM). To improve estimation to HIV acquisition, we created a composite score using questions from routine survey of 3588 MSM in Beijing, China. The HIV prevalence was 13.4%. A risk scoring tool using penalized maximum likelihood multivariable logistic regression modeling was developed, deploying backward step-down variable selection to obtain a reduced-form model. The full penalized model included 19 sexual predictors, while the reduced-form model had 12 predictors. Both models calibrated well; bootstrap-corrected c-indices were 0.70 (full model) and 0.71 (reduced-form model). Non-Beijing residence, short term living in Beijing, illegal drug use, multiple male sexual partners, receptive anal sex, inconsistent condom use, alcohol consumption before sex, and syphilis infection were the strongest predictors of HIV infection. Discriminating higher-risk MSM for targeted HIV prevention programming using a validated risk score could improve the efficiency of resource deployment for educational and risk reduction programs. A valid risk score can also identify higher risk persons into prevention and vaccine clinical trials, which would improve trial cost efficiency. PMID- 29786771 TI - Analysis of Letter Representation Using Latin and Arabic Scripts: A Masked Priming Study. AB - Reading plays an essential role in our everyday lives. The aim of this study is to investigate how letters are represented in the brain using the unique characteristics of the Arabic language, which can be written with 2 different scripts. The hypothesis proposed is that the processing of script is sound based: Phonology is what determines letter identity. Using a forward-masked priming paradigm, we showed that Latin-script primes facilitated the recognition of subsequent Arabic-script targets which differed in orthography but shared phonology, thus suggesting a common level of phonological processing. In addition, semantic priming effects were controlled for. The findings thus confirmed our hypothesis and showed that letters that represent the same sound are processed similarly. PMID- 29786772 TI - Upstaging to invasive ductal carcinoma after mastectomy for ductal carcinoma in situ: predictive factors and role of sentinel lymph node biopsy. AB - BACKGROUND: The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS. METHODS: The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed. RESULTS: Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0-3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis. CONCLUSIONS: Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0-3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB. PMID- 29786770 TI - The Extract of Leonurus sibiricus Transgenic Roots with AtPAP1 Transcriptional Factor Induces Apoptosis via DNA Damage and Down Regulation of Selected Epigenetic Factors in Human Cancer Cells. AB - The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down regulation of mRNA levels. Additionally, we demonstrated differences in the content of compounds in the tested extracts by HPLC analysis with ATPAP1 construct and without. Both the tested extracts showed anticancer properties and the better results were observed for AtPAP1 with transcriptional factor root extract; this effect could be ascribed to the presence of higher condensed phenolic acids such as neochlorogenic acid, chlorogenic acids, ferulic acid, caffeic acid and p-coumaric acid. Further studies with AtPAP1 (with the transcriptional factor from Arabidopisi thaliana) root extract which showed better activities in combination with anticancer drugs are needed. PMID- 29786773 TI - Survival analysis according to period and analysis of the factors influencing changes in survival in patients with recurrent breast cancer: a large-scale, single-center study. AB - BACKGROUND: We performed this study to analyze changing survival patterns regarding recurrent breast cancer in Korea during the last 16 years (1993-2008). We also sought to determine factors possibly influencing outcomes and changes over time in the duration of survival after recurrence. METHODS: We retrospectively analyzed 9671 patients with breast cancer treated between January 1993 and December 2008, comparing the periods 1993-2002 and 2003-2008.We retrospectively reviewed the collected database including the age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment modalities, type of recurrence, and follow-up period. RESULTS: There were 1944 cases (20.1%) of recurrence. Median age at the first recurrence was 49.5 years (range 21.8-92.9). Median follow-up was 28.8 months (range 0-228.0) from the time of relapse. Median survival time was 35.0 months. Survival after recurrence (SAR) significantly improved in 2003-2008 compared to that in 1993 2002. Median survival time increased from 27.6 months in the period I to 42.3 months in period II (p = 0.001). Independent prognostic factors after the first recurrence by multivariate analysis were age at diagnosis, tumor size, nodal status, tumor grade, subtype, anti-hormonal therapy, time at diagnosis, and disease-free interval. CONCLUSIONS: Outcomes of breast cancer have been improving recently, and survival time after the first recurrence of breast cancer has steadily increased in recent decades. We confirmed that advances in treatments have contributed to this improvement in survival after the first recurrence. PMID- 29786775 TI - Stormram 4: An MR Safe Robotic System for Breast Biopsy. AB - Suspicious lesions in the breast that are only visible on magnetic resonance imaging (MRI) need to be biopsied under MR guidance with high accuracy and efficiency for accurate diagnosis. The aim of this study is to present a novel robotic system, the Stormram 4, and to perform preclinical tests in an MRI environment. Excluding racks and needle, its dimensions are 72 * 51 * 40 mm. The Stormram 4 is driven by two linear and two curved pneumatic stepper motors. The linear motor is capable of exerting 63 N of force at a pressure of 0.65 MPa. In an MRI environment the maximum observed stepping frequency is 30 Hz (unloaded), or 8 Hz when full force is needed. The Stormram 4's mean positioning error is 0.73 +/- 0.47 mm in free air, and 1.29 +/- 0.59 mm when targeting breast phantoms in MRI. Excluding the off-the-shelf needle, the robot is inherently MR safe. The robot is able to accurately target lesions under MRI guidance, reducing tissue damage and risk of false negatives. These results are promising for clinical experiments, improving the quality of healthcare in the field of MRI-guided breast biopsies. PMID- 29786774 TI - Computational Fluid Dynamics Modeling of the Human Pulmonary Arteries with Experimental Validation. AB - Pulmonary hypertension (PH) is a chronic progressive disease characterized by elevated pulmonary arterial pressure, caused by an increase in pulmonary arterial impedance. Computational fluid dynamics (CFD) can be used to identify metrics representative of the stage of PH disease. However, experimental validation of CFD models is often not pursued due to the geometric complexity of the model or uncertainties in the reproduction of the required flow conditions. The goal of this work is to validate experimentally a CFD model of a pulmonary artery phantom using a particle image velocimetry (PIV) technique. Rapid prototyping was used for the construction of the patient-specific pulmonary geometry, derived from chest computed tomography angiography images. CFD simulations were performed with the pulmonary model with a Reynolds number matching those of the experiments. Flow rates, the velocity field, and shear stress distributions obtained with the CFD simulations were compared to their counterparts from the PIV flow visualization experiments. Computationally predicted flow rates were within 1% of the experimental measurements for three of the four branches of the CFD model. The mean velocities in four transversal planes of study were within 5.9 to 13.1% of the experimental mean velocities. Shear stresses were qualitatively similar between the two methods with some discrepancies in the regions of high velocity gradients. The fluid flow differences between the CFD model and the PIV phantom are attributed to experimental inaccuracies and the relative compliance of the phantom. This comparative analysis yielded valuable information on the accuracy of CFD predicted hemodynamics in pulmonary circulation models. PMID- 29786776 TI - A Framework for Image-Based Modeling of Acute Myocardial Ischemia Using Intramurally Recorded Extracellular Potentials. AB - The biophysical basis for electrocardiographic evaluation of myocardial ischemia stems from the notion that ischemic tissues develop, with relative uniformity, along the endocardial aspects of the heart. These injured regions of subendocardial tissue give rise to intramural currents that lead to ST segment deflections within electrocardiogram (ECG) recordings. The concept of subendocardial ischemic regions is often used in clinical practice, providing a simple and intuitive description of ischemic injury; however, such a model grossly oversimplifies the presentation of ischemic disease-inadvertently leading to errors in ECG-based diagnoses. Furthermore, recent experimental studies have brought into question the subendocardial ischemia paradigm suggesting instead a more distributed pattern of tissue injury. These findings come from experiments and so have both the impact and the limitations of measurements from living organisms. Computer models have often been employed to overcome the constraints of experimental approaches and have a robust history in cardiac simulation. To this end, we have developed a computational simulation framework aimed at elucidating the effects of ischemia on measurable cardiac potentials. To validate our framework, we simulated, visualized, and analyzed 226 experimentally derived acute myocardial ischemic events. Simulation outcomes agreed both qualitatively (feature comparison) and quantitatively (correlation, average error, and significance) with experimentally obtained epicardial measurements, particularly under conditions of elevated ischemic stress. Our simulation framework introduces a novel approach to incorporating subject-specific, geometric models and experimental results that are highly resolved in space and time into computational models. We propose this framework as a means to advance the understanding of the underlying mechanisms of ischemic disease while simultaneously putting in place the computational infrastructure necessary to study and improve ischemia models aimed at reducing diagnostic errors in the clinic. PMID- 29786777 TI - The Biomechanics of the Inter-Lamellar Matrix and the Lamellae During Progression to Lumbar Disc Herniation: Which is the Weakest Structure? AB - While microstructural observations have improved our understanding of possible pathways of herniation progression, no studies have measured the mechanical failure properties of the inter-lamellar matrix (ILM), nor of the adjacent lamellae during progression to herniation. The aim of this study was to employ multiscale, biomechanical and microstructural techniques to evaluate the effects of progressive induced herniation on the ILM and lamellae in control, pre herniated and herniated discs (N = 7), using 2 year-old ovine spines. Pre herniated and herniated (experimental) groups were subjected to macroscopic compression while held in flexion (13 degrees ), before micro-mechanical testing. Micro-tensile testing of the ILM and the lamella from anterior and posterolateral regions was performed in radial and circumferential directions to measure failure stress, modulus, and toughness in all three groups. The failure stress of the ILM was significantly lower for both experimental groups compared to control in each of radial and circumferential loading directions in the posterolateral region (p < 0.032). Within each experimental group in both loading directions, the ILM failure stress was significantly lower by 36% (pre-herniation), and 59% (herniation), compared to the lamella (p < 0.029). In pre-herniated compared to control discs, microstructural imaging revealed significant tissue stretching and change in orientation (p < 0.003), resulting in a loss of distinction between respective lamellae and ILM boundaries. PMID- 29786778 TI - Development and characterization of microsatellite markers for endangered species Stipa pennata (Poaceae) and their usefulness in intraspecific delimitation. AB - Stipa pennata (Poaceae), has become a rare and endangered species in Central Europe due habitat loss and fragmentation. This species is characterized by high morphological variability, which has resulted in the description of numerous intraspecific taxa. The aim of present work is to develop microsatellite markers useful in population genetics studies as well as in intraspecific taxonomy of S. pennata s.l. We developed ten microsatellite markers using Illumina high throughput. Polymorphism at each marker was evaluated using 4-15 individuals from four morphotypes of S. pennata s.l. Seven markers showed polymorphism while three were monomorphic. The number of alleles per locus ranged from 7 to 12, and the observed and expected heterozygosity varied from 0.000 to 1.000 and 0.000 to 0.8670, respectively. Our results confirm that three of four studied morphotypes are genetically distinct. The microsatellite markers developed here will be useful for evaluating levels of genetic diversity and differentiation, to study gene flow, population dynamics and in future conservation studies as well as for intraspecific delimitation of morphologically similar taxa within S. pennata s.l. PMID- 29786779 TI - DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis. AB - AIM AND OBJECTIVE: Regulation of microRNA gene expression by DNA methylation may represent a key mechanism to drive cardiac fibrosis progression. Cardiac fibroblast autophagy is the primary source of cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we found that DNMT3A suppression of the microRNA-200b (miR-200b) through pathway leads to cardiac fibroblast autophagy in cardiac fibrosis. METHODS: To understand the impact of DNMT3A on miR-200b at cardiac fibrosis, the rat cardiac fibrosis model was established via the abdominal aortic coarctation. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of DNMT3A, miR 200b, collagen I was measured by western blotting, immunohistochemistry and qRT PCR. Gain- or loss-of-function approaches were used to manipulate DNMT3A and miR 200b. RESULTS: DNMT3A level was upregulated and negatively correlated with miR 200b expression in fibrosis tissues and cardiac fibroblast. We found that autophagy was activated by miR-200b inhibitor and inactivated by miR-200b mimic in the rat cardiac fibroblast. Knockdown of DNMT3A notably increased the expression of miR-200b. CONCLUSIONS: Taken together, these findings indicate that DNMT3A regulation of miR-200b controls cardiac fibroblast autophagy during cardiac fibrosis and provide a basis for the development of therapies for cardiac fibrosis. PMID- 29786780 TI - Correction to: The Italian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). AB - The family name of author Francesco La Torre was incorrect in the published article. The correct family name should read as La Torre F. PMID- 29786782 TI - Preclinical impact of high dose intermittent antiangiogenic tyrosine kinase inhibitor pazopanib in intrinsically resistant tumor models. AB - Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently. The rationale is that using such protocols, antitumor efficacy could be enhanced by direct tumor cell targeting effects in addition to inhibiting tumor angiogenesis. To test this, we employed two human tumor xenograft models, both of which manifest intrinsic resistance to pazopanib when it is administered continuously: the VHL-wildtype SN12-PM6-1 renal cell carcinoma (RCC) and the metastatic MDA-MB-231/LM2-4 variant breast cancer cell line, when treated as distant metastases. We evaluated four different doses and schedules of pazopanib in the context of primary tumors and advanced metastatic disease, in both models. The RCC model was not converted to drug sensitivity using the intermittent protocol. Using these protocols did not enhance the efficacy when treating primary LM2-4 tumors. However, one of the high-dose intermittent pazopanib protocols increased median survival when treating advanced metastatic disease. In conclusion, these results overall suggest that primary tumors showing sensitivity to continuous pazopanib treatment may predict response to this drug when given at high doses intermittently in the context of advanced metastatic disease, that are otherwise resistant to the conventional protocol. PMID- 29786781 TI - The EJES-3D tool for personalized prescription of exercise in axial spondyloarthritis through multimedia animations: pilot study. AB - To develop and evaluate a web application based on multimedia animations, combined with a training program, to improve the prescription of exercises in spondyloarthritis (SpA). After a review of exercises included in the main clinical trials and recommendations of international societies, a multidisciplinary team-rehabilitators, rheumatologists, physiotherapists, computer scientists and graphic designers-developed a web application for the prescription of exercises (EJES-3D). Once completed, this was presented to 12 pairs of rehabilitators-rheumatologists from the same hospital in a workshop. Knowledge about exercise was tested in rheumatologists before and 6 months after the workshop, when they also evaluated the application. The EJES-3D application includes 38 multimedia videos and allows prescribing predesigned programs or customizing them. A patient can consult the prescribed exercises at any time from a device with internet connection (mobile, tablet, or computer). The vast majority of the evaluators (89%) were satisfied or very satisfied and considered that their expectations regarding the usefulness of the web application had been met. They highlighted the ability to tailor exercises adapted to the different stages of the disease and the quality and variety of the videos. They also indicated some limitations of the application and operational problems. The EJES 3D tool was positively evaluated by experts in SpA, potentially the most demanding group of users with the most critical capacity. This allows a preliminary validation of the contents, usefulness, and ease of use. Analyzing and correcting the errors and limitations detected is allowing us to improve the EJES-3D tool. PMID- 29786784 TI - Generation of Prostate Cancer Patient-Derived Xenografts to Investigate Mechanisms of Novel Treatments and Treatment Resistance. AB - Treatment advances lead to survival benefits of patients with advanced prostate cancer. These treatments are highly efficacious in a subset of patients; however, similarly to other cancers, after initial responses the tumors develop resistance (acquired resistance) and the patients succumb to the disease. Furthermore, there is a subset of patients who do not respond to the treatment at all (de novo resistance). Preclinical testing using patient-derived xenografts (PDXs) has led to successful drug development, and PDXs will continue to provide valuable resources to generate clinically relevant data with translational potential. PDXs demonstrate tumor heterogeneity observed in patients, preserve tumor microenvironment architecture, and provide clinically relevant treatment responses. In view of the evolving biology of the advanced prostate cancer associated with new treatments, PDXs representing these new tumor phenotypes are urgently needed for the study of treatment responses and resistance. In this chapter, we describe methodologies used to establish prostate cancer PDXs and use of these PDXs to study de novo and acquired resistance. PMID- 29786783 TI - A xenograft model for venous malformation. AB - Vascular malformations are defects caused by the abnormal growth of the vasculature. Among them, venous malformation (VM) is an anomaly characterized by slow-flow vascular lesions with abnormally shaped veins, typically in sponge-like configuration. VMs can expand over years causing disfigurement, obstruction of vital structures, thrombosis, bleeding, and pain. Treatments have been very limited and primarily based on supportive care, compression garments, sclerotherapy, and/or surgical resection. Sirolimus treatment has recently shown efficacy in some patients with complicated vascular anomalies, including VMs. Activating somatic TIE2 gene mutations have been identified in up to 60% of VMs and PIK3CA mutations have been found in another 25%. Here, we report a xenograft model of VM that reflects the patients' mutation heterogeneity. First, we established a protocol to isolate and expand in culture endothelial cells (VM-EC) from VM tissue or VM blood of nine patients. In these cells, we identified somatic mutations of TIE2, PIK3CA, or a combination of both. Both TIE2 and PIK3CA mutations induced constitutive AKT activation, while TIE2 mutations also showed high MAPK-ERK signaling. Finally, VM-EC implanted into immune-deficient mice generated lesions with ectatic blood-filled channels with scarce smooth muscle cell coverage, similar to patients' VM. This VM xenograft model could be instrumental to test the therapeutic efficacy of Sirolimus in the presence of the different TIE2 or PIK3CA mutations or to test for efficacy of additional compounds in targeting the specific mutated protein(s), thus enabling development of personalized treatment options for VM patients. PMID- 29786785 TI - Methods to Study Angiogenesis in a Mouse Model of Prostate Cancer. AB - Angiogenesis is one important hallmark of cancer progression which explains the relevance of developing methods to efficiently analyze the neo-angiogenic process. In this report we make use of the transgenic adenocarcinoma of the murine prostate (TRAMP) model, considered a good model for studying clinical prostate cancer progression, to describe in detail the methods used to study angiogenesis in this type of solid tumor development. In this report we provide step-by-step procedures on the basis of previous work in our laboratory for: the mouse urogenital sinus (UGS) collection; microdissection of the prostate; preparation of the prostatic samples for immunofluorescence (to analyze vascular density, morphology, maturation, functionality, hypoxia, and others); preparation of prostatic samples to histopathological analysis and/or immunohistochemistry; and endothelial and vascular mural cell sorting and isolation by fluorescent associated cell sorting (FACS) to further analysis (mRNA, protein, or other) or to maintain in culture. PMID- 29786786 TI - Methodologies Applied to Establish Cell Cultures in Prostate Cancer. AB - This chapter focuses on primary cultures of the human malignant prostate. Current abilities to isolate and culture stem cells, transit-amplifying cells, and secretory luminal cells are described. Advantages and limitations of this model system are also discussed. PMID- 29786787 TI - Protocols for Migration and Invasion Studies in Prostate Cancer. AB - Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion. PMID- 29786788 TI - Transplantable Animal Studies and Whole-Body Optical Imaging in Prostate Carcinoma. AB - Current treatments of advanced prostate cancer only marginally increase overall survival and can be regarded as predominantly palliative. Hence, there is an urgent need for novel therapeutic strategies for the treatment of primary tumors and, more importantly perhaps, for the prevention of tumor progression and metastasis formation. Clinically relevant preclinical models are therefore urgently needed. An ideal, clinically relevant preclinical model would mimic the genetic and phenotypic changes that occur at the different stages of human prostate cancer progression and subsequent metastasis. In this chapter, transplantable xenograft prostate cancer models are described, in which human prostate cancer cells are transplanted into host animals (e.g., immune-deficient mice). Cancer cells can be administered to the small laboratory animals in various ways, including inoculation of the prostate tumor cells subcutaneously, at the anatomical site of origin (orthotopically), or at the metastatic site. In addition, we describe imaging methods suitable for small laboratory animals with emphasis on optical imaging (bioluminescence and fluorescence). PMID- 29786789 TI - Protocols for Tissue Microarrays in Prostate Cancer Studies. AB - Tissue microarray (TMA) technology is a method for high-throughput analysis of tissue biomarkers, commonly used in translational cancer research. TMAs allow performing a variety of in situ applications on hundreds of tissue samples simultaneously using the same protocols as for conventional slides. Thereby, precious material from patient samples remains largely preserved while costs in resources and time in laboratory processing decrease. Therefore, a TMA is a powerful tool to identify and study biomarkers that may have a potential diagnostic, prognostic, and predictive value. Depending on the research question, there are different types of TMAs, such as progression TMA, outcome TMA, and tumor heterogeneity TMA. Since the first introduction of the TMA method almost 20 years ago, most laboratories used manual tissue arrayers for manufacturing. Nowadays, automatic or semiautomatic devices are commercially available, which largely facilitates the technical construction. However, preparatory work remains the most time-consuming part in preparing TMAs. This chapter focuses on issues involved in design and construction of prostate cancer TMAs. PMID- 29786790 TI - Functional Studies on Steroid Receptors. AB - Nuclear receptors play an important role in prostate cancer and the androgen receptor is a key transcription factor in regulation of cellular events. Androgen receptor-associated coregulators may be upregulated or downregulated in prostate cancer. Altered expression of regulators may potentiate androgen-induced proliferation, migration, and invasion. Therapies aimed to modulate the function of coregulators in prostate cancer may be based on the use of small molecule inhibitors. Expression and function of AR-associated proteins could be investigated after overexpression and gene silencing followed by hormonal treatment, real-time RT-PCR and ChIP. PMID- 29786791 TI - Protocols for Studies on TMPRSS2/ERG in Prostate Cancer. AB - TMPRSS2/ERG is the most common type of gene fusions found in human prostate cancer. There are two important features of TMPRSS2/ERG fusions. One is that these gene fusions lead to ectopic expression of ERG, an ETS family transcription factor, in prostate epithelial cells from the 5' control region of an androgen/estrogen dual-responsive gene, TMPRSS2; the other is that ~60% of these fusions are generated via intrachromosomal deletion of the interstitial region between TMPRSS2 and ERG. To recapitulate these important aspects of TMPRSS2/ERG fusions, we generated several TMPRSS2/ERG knockin mouse models based on the endogenous Tmprss2 locus. We found that TMPRSS2/ERG represents an early event in prostate tumorigenesis, by sensitizing prostate cells for cooperation with other oncogenic events, such as PTEN-deficiency. We also found that the interstitial region between TMPRSS2 and ERG harbors at least one prostate tumor suppressor, ETS2, whose loss contributes to prostate cancer progression. In this protocol, we describe how these knockin mouse models can be utilized to study roles of TMPRSS2/ERG fusions in prostate cancer development both in vivo and in vitro. PMID- 29786792 TI - Protocols for the Study of Taxanes Chemosensitivity in Prostate Cancer. AB - Prostate cancer is major cause of cancer-related death among men in Western countries. Locally advanced prostate cancers are treated with castration therapy, which is initially effective, but after months the disease progresses to a hormone-refractory state whose treatment is chemotherapy based on taxanes. Although taxanes improve the survival of patients with castration-resistant prostate cancers, these patients often develop chemotherapy resistance, and new therapeutic strategies are necessary. Taxanes exert their action through interaction with beta-tubulin which triggers cell cycle arrest in mitosis and the subsequent induction of the intrinsic apoptotic pathway. Since taxanes are widely used for the treatment of advanced prostate cancers, we present in this chapter protocols that allow the study of the prostate cancer sensitivity as well as determine the mechanisms of resistance to these chemotherapeutic agents. PMID- 29786793 TI - A Method for Prostate and Breast Cancer Cell Spheroid Cultures Using Gelatin Methacryloyl-Based Hydrogels. AB - Modern tissue engineering technologies have delivered tools to recreate a cell's naturally occurring niche in vitro and to investigate normal and pathological cell-cell and cell-niche interactions. Hydrogel biomaterials mimic crucial properties of native extracellular matrices, including mechanical support, cell adhesion sites and proteolytic degradability. As such, they are applied as 3D cell culture platforms to replicate tissue-like architectures observed in vivo, allowing physiologically relevant cell behaviors. Here we review bioengineered 3D approaches used for prostate and breast cancer. Furthermore, we describe the synthesis and use of gelatin methacryloyl-based hydrogels as in vitro 3D cancer model. This platform is used to engineer the microenvironments for prostate and breast cancer cells to study processes regulating spheroid formation, cell functions and responses to therapeutic compounds. Collectively, these bioengineered 3D approaches provide cell biologists with innovative pre-clinical tools that integrate the complexity of the disease seen in patients to advance our knowledge of cancer cell physiology and the contribution of a tumor's surrounding milieu. PMID- 29786794 TI - Protocols for Studies on Genetically Engineered Mouse Models in Prostate Cancer. AB - Cancer studies have entered an era that is heavily focused on the contribution of the tumor microenvironment. For this reason, in vivo experimentation in an immunodeficient model system is no longer fit for purpose. As a consequence, numerous genetically engineered mouse models (GEMMs) which self-develop tumors have been developed to allow experiments to be performed in a fully immunocompetent setting. One of the most commonly used technologies is Cre-loxP recombination due to its unique ability to control target gene expression in a specified tissue type. However, the major limitation of these models remains the inability to generate sufficient numbers of age-matched mice for a synchronized experimental start date. For this reason, the derivation of cell lines from genetically modified murine prostate tissue is desirable and allows for the generation of syngeneic models via subcutaneous or orthotopic injection. PMID- 29786795 TI - Protocols for Studies on Stromal Cells in Prostate Cancer. AB - Interactions between tumor cells and fibroblasts play a pivotal role in cancer development and progression. Indeed, the paracrine communication between these two cell types is known to have physiological effects that alter carcinogenic and metastatic potential. An often overlooked player in these interactions is the involvement of the extracellular matrix (ECM). The network of ECM proteins secreted from fibroblasts is reportedly altered with cancer initiation and progression, and in several cases has been associated with patient outcome. The androgen receptor (AR) is one such example and has been shown to be a dynamic and inducible regulator of ECM production. Contemporary assessment of dynamic multicellular interactions leading to cancer initiation and progression necessitates 3D in vitro modeling to better mimic the in vivo environment. In the current chapter, we describe some simple approaches to generate 3D models of fibroblast-produced ECM, how hormone manipulation of fibroblasts can lead to production of different ECMs, and how these ECM models can be used to test processes implicated in cancer progression and metastasis. PMID- 29786796 TI - Techniques for Evaluation of AR Transcriptional Output and Recruitment to DNA. AB - Steroid receptors are ligand activated transcription factors whose promoter specificity is regulated by a broad set of coregulators and pioneer factors. Corepressors and coactivators determine receptors' recruitment to specific regulatory elements and ultimately their transcriptional output. Using androgen receptor (AR) and NCOR1 corepressor as examples, this chapter describes experimental approaches to evaluate recruitment of steroid receptors and their coregulators to DNA and to determine coregulator contribution to the transcriptional output of the receptor. The chromatin immunoprecipitation assay, or ChIP, quantifies protein-DNA interaction in the cellular chromatin environment. Here, we describe a protocol to measure NCOR1 recruitment to AR binding sites of interest using ChIP. Gene Set Enrichment Analysis, GSEA, is a computational technique to determine whether a defined gene set is significantly represented among changes in gene expression between two biological groups. As an example, we examine whether AR repressed genes are significantly represented among genes altered by the NCOR1 knockout. PMID- 29786797 TI - NMR-Based Prostate Cancer Metabolomics. AB - Prostate cancer is the second most common malignancy, and the fifth leading cause of cancer-related death among men, worldwide. A major unsolved clinical challenge in prostate cancer is the ability to accurately distinguish indolent cancer types from the aggressive ones. Reprogramming of metabolism is now a widely accepted hallmark of cancer development, where cancer cells must be able to convert nutrients to biomass while maintaining energy production. Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues, or organisms. Nuclear magnetic resonance (NMR) spectroscopy is commonly applied in metabolomics studies of cancer. This chapter provides protocols for NMR-based metabolomics of cell cultures, biofluids (serum and urine), and intact tissue, with concurrent advice for optimal biobanking and sample preparation procedures. PMID- 29786799 TI - ? PMID- 29786798 TI - Studies on Steroid Receptor Coactivators in Prostate Cancer. AB - High expression of several androgen receptor coactivators is frequently reported in prostate cancer. Coactivators such as p300/CBP are involved in modulation of androgen receptor activity by increasing the effects of androgenic hormones and enhancing agonistic activity of antiandrogens. Studies in the field of prostate cancer frequently examined the role of p300/CBP and SRC-1 (NCOA1). In addition to their effects on steroid receptor activity, coactivators may influence other cellular functions such as migration and invasion. Steroid receptor coactivators may target various downstream genes, thus modulating proliferative and migratory responses in specific prostate cancer models. This chapter will focus on methodologies used to analyze the role of steroid receptor coactivators in prostate cancer. PMID- 29786800 TI - ? PMID- 29786802 TI - [Treatment with neurostimulation and ketogenic diet for people with medically refractory epilepsy]. AB - For some people with medically refractory epilepsy adjunct treatment with neurostimulation and ketogenic diet can be an option. Vagal nerve stimulation, VNS, consists of chronic intermittent electrical stimulation of the vagus nerve. VNS is effective and well tolerated in adolescents and adults. There is insufficient evidence on the efficacy of deep brain stimulation, DBS, and brain responsive neurostimulation, RNS. Ketogenic diet is an established treatment in epilepsy with an increased number of indications, especially in neurometabolic diseases, where dietary therapy can completely eliminate epilepsy and improve cognitive and motor development. Ketogenic diet is a calculated diet consisting of a high amount of fat, the daily need of protein and a minimum of carbohydrates. The fat is converted to ketone bodies and transported across the blood-brain barrier to be used as an alternative energy source in the brain. Strictly calculated menus, regular monitoring and support from a team of dietician, nurse and physician are required. PMID- 29786801 TI - [Epilepsy: incidens, prevalens and causes]. AB - Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy. PMID- 29786803 TI - ? PMID- 29786804 TI - [Protein deficiency - a rare nutrient deficiency]. AB - There is a widespread myth that we have to be careful about what we eat so that we do not cause protein deficiency. We know today that it is virtually impossible to design a calorie-sufficient diet, whether it is based on meat, fish, eggs, various vegetarian diets or even unprocessed whole natural plant foods, which is lacking in protein and any of the amino acids. The body is capable of taking incomplete proteins and making them complete by utilizing the amino acid recycling mechanism. The majority of amino acids absorbed from the intestinal tract are derived from recycled body protein. Research shows that high levels of animal protein intake may significantly increase the risk of premature mortality from all causes, among them cardiovascular diseases, cancer and type 2 diabetes. PMID- 29786805 TI - [Classification of seizures and epilepsies]. AB - In 2017 the International League Against Epilepsy (ILAE) published position papers outlining new classifications of seizures and epilepsies. The aims of the new documents are to encompass advances in the field, provide a conceptual framework for future developments, and facilitate communication. In practice, the terminology is somewhat revised. For seizures the terms "partial" and "simple/complex" are replaced by "focal" and "aware/impaired awareness". The classification of a patient's epilepsy is based on seizures types (e.g. focal or generalized) as well as aetiology (e.g. structural, immune-mediated, genetic) and epilepsy syndrome. The present article describes the Swedish translation, endorsed by the Swedish Epilepsy Society. PMID- 29786806 TI - ? PMID- 29786807 TI - [Pharmacotherapy of epilepsy]. AB - Pharmacotherapy of epilepsy is usually initiated after two or more unprovoked seizures, a decision that should be made after assessment of the individual risk of further seizures. Antiepileptic drugs (AEDs) are selected based on documented efficacy for the type of seizures, the epilepsy and possible epilepsy syndrome of the patient, taking potential adverse effects and comorbidity into account. For many AEDs, the mechanisms of action are incompletely understood. More than half of patients with newly diagnosed epilepsy achieve sustained seizure freedom with their first or second drug trials. After a prolonged time of seizure freedom discontinuation of therapy may be considered; the risk of relapse after drug withdrawal can be estimated on the basis of a number of clinical factors. The informed patient's attitude is essential in all therapy decisions. Treatment is still largely symptomatic, but the future may involve a greater degree of disease modifying precision medicine. PMID- 29786808 TI - [Status epilepticus in children and adults]. AB - Status epilepticus, a condition with prolonged or repeated seizures, is a common neurological emergency with significant morbidity and mortality. This text outlines the treatment and initial work-up for convulsive and non-convulsive status epilepticus in adults and children. The most serious form is convulsive (tonic-clonic) status epilepticus, which requires rapid treatment and work-up. Bensodiazepines are the preferred initial treatment, while antiepileptic drugs and anesthetics are added if seizures continue. For other forms of status epilepticus, the treatment depends on the type of seizures and the patient's general condition. Etiological work-up is essential in any case of status epilepticus. Effective treatment and work-up in status epilepticus requires a defined treatment protocol and multidisciplinary cooperation. PMID- 29786809 TI - [Diagnosing epileptic seizures and epilepsy]. AB - There are many episodic conditions which may be confused with epileptic seizures. The diagnosis of epileptic seizures is still dependent on a good history and witness report, as well as good knowledge of seizure semiology, and of the symptoms of a variety of differential diagnostic conditions. The principal differential diagnoses in adults and children are outlined in this review. The diagnostic problems do not exist only initially, so it is important to reconsider the diagnosis when deemed relevant. The possibility of home video recordings of recurring attacks may be helpful. Neuroimaging and interictal EEG cannot confirm or exclude epilepsy but can demonstrate relevant pathology and are of prognostic importance. PMID- 29786810 TI - [Epilepsy and comorbid neurodevelopmental disorders]. AB - In children and adults with epilepsy, it is important to be aware of and diagnose common comorbidities that may have a large impact on quality of life. Comorbid neurodevelopmental disorders include intellectual disability, autism, and attention deficit hyperactivity disorder (ADHD). Depression and anxiety are common findings, and also the risk of psychosis is increased. The medication used to treat these comorbidities is found to be effective with little risks of seizure exacerbation, i.e. medication with methylphenidate, selective serotonin reuptake inhibitors (SSRIs) and second generation neuroleptics. However, for every combination of antiepileptic drugs with new medication, the possibility of drug interactions should be kept in mind. Transition from childhood to adult medicine must include adequate treatment and follow-up of comorbid conditions. PMID- 29786811 TI - [50 percent of patients who had epilepsy surgery are seizure-free]. AB - About one third of patients with epilepsy do not become seizure-free despite medication. For some, resective epilepsy surgery is the treatment of choice. There are three randomized controlled trials, with positive results at a follow up of 1-2 years: two on temporal lobe resections on adults and young people and one on all types of epilepsy surgery on children. Since 1990 all epilepsy surgery procedures in Sweden are reported to the Swedish Epilepsy Surgery Register, now with data on almost 1500 patients. Two years after surgery about 50% of adults and children are seizure-free, and another 10% have been so during the last year. After 10 seizure-free years 40% of adults and 80% of children have stopped medication. All patients with pharmacoresistant focal epilepsy should be referred to the regional epilepsy team for evaluation and possibly epilepsy surgery. Small children should be referred to the regional pediatric team early, since the epileptic seizures may hamper their development. PMID- 29786812 TI - The microRNA expression profile in rat lung tissue early after burn injury. AB - BACKGROUND: Severe burn causes acute lung injury in many victims, but the related mechanisms have been barely investigated. microRNAs (miRNAs) important regulators in numerous physiological and pathophysiological process. However, the roles of miRNAs in burn lung injury are untested. METHODS: Six healthy male Sprague-Dawley rats were randomly assigned into burn and sham groups. Lung injury was evaluated by hematoxylin and eosin (HE) staining at 24 h after injury. Differentially expressed miRNAs were determined by array hybridization and verified by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis was undertaken to predict the target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were employed to identify potentially related biological processes and pathways, respectively. Neutrophil infiltration and apoptosis of the lung were confirmed by immunohistochemical staining of myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: HE sections showed obvious lung injury, and 21 upregulated and three downregulated miRNAs were detected. Target genes of these miRNAs were most highly enriched in inflammation and apoptosis related GO biological processes and pathways. Inflammation and apoptosis were confirmed by MPO and TUNEL staining. CONCLUSION: The differentially expressed miRNAs most likely participate in burn-induced lung injury by being involved in inflammation and apoptosis. PMID- 29786813 TI - Prediction of mortality in pediatric traumatic brain injury: Implementations from a tertiary pediatric intensive care facility. AB - BACKGROUND: To explore the mortality risk factors of traumatic brain injury in pediatric intensive care unit admissions. METHODS: Eighty-eight children (categorized using the Glasgow Coma Scale) between September 2014 and December 2016 were analyzed. Emergency department and intensive care course, treatment strategies, axonal injury, intubation and tracheostomy rates, length of intensive care and hospitalization, Rotterdam-CT scores, injury severity scores, and PRISM III scores were recorded. RESULTS: Older age was associated with trauma severity (p=0.010). Target serum osmolality was reached at 8.5 (3.5-40) hours in patients undergoing anti-edema therapy. ICP-monitoring rates was 8%; in absence of ICP monitorization clinical follow-up was performed through repeated brain tomographies. Axonal injury was associated with prolonged intubation, intensive care and hospital stay (p<0.001, p<0.001, p=0.030). Six children required tracheostomy at 14.33+/-1.03 days; decannulations were performed within 6 months in five children. CONCLUSION: Mortality rate was 12.5%; six patients progressed to brain death with organ donor approvals in five. Initial hypotension, lung contusion, injury severity scores and Rotterdam-CT scores were related with mortality. Rotterdam-CT score was determined as the independent risk factor for mortality; one increment in the score increased the odd of recovery by 20.334 times (%95 CI 1.999-206.879). ISS score was also borderline significant (p=0.052; OR:1.195 %95 CI 0.999-1.430). PMID- 29786814 TI - Predictive value of preoperative neutrophil-to-lymphocyte ratio while detecting bowel resection in hernia with intestinal incarceration. AB - BACKGROUND: The aim of this study was to evaluate the relationship between preoperative hematological inflammatory markers of the patients who underwent a surgery for incarcerated hernia and intestinal resection requirement. METHODS: The data of 102 patients who underwent a surgery for incarcerated hernia were retrospectively evaluated. Whole blood cell counts were preoperatively measured, and operation types and pathology results were recorded. The patients with intestinal resections were compared with those without any resection in terms of leukocyte number, neutrophil rate, red cell distribution width (RDW), platelet distribution width, neutrophil-to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). RESULTS: Eighty-one patients were operated for incarcerated groin hernia, 17 for incarcerated umbilical hernia, and 4 for incarcerated incisional hernia. Twenty-six patients (25%) had intestinal resections; in 4 of them, intestinal perforation was detected. In patients with intestinal resections,the neutrophil rate, PDW, NLR, and PLR values were significantly higher than those in the patients without any resections. CONCLUSION: High NLR rates, certainly with clinical correlation, can be used as a biomarker to predict intestinal necrosis and the need for intestinal resection in patients who will undergo surgery for incarcerated hernia, particularlyin situations with lacking radiological imaging methods. PMID- 29786815 TI - Role of circulating microRNAs in acute appendicitis. AB - BACKGROUND: Acute appendicitis (AA) is a momentous, emergency, surgical pathology that has still been investigated for both etiopathogenetic unknowns and challenges in diagnosis. Presently, there is little information about the role of microRNAs (miRNAs), which have basic biological functions in the cell, can be a marker, and are associated with various pathologies, in patients with AA. The aim of this study was to investigate the expressions of some miRNAs in AA. METHODS: Overall, 41 miRNAs were screened in 48 individuals comprising 24 patients with AA and 24 healthy controls at Erciyes University Genome and Stem Cell Center (GENKOK). The obtained data were analyzed using appropriate statistical methods. RESULTS: miR-29c-3p was found to be increased 2-fold during the first 4-6 h in AA, and this increase was revealed to be statistically significant compared with healthy individuals. Similarly, expressions of let-7b-5p, let-7i-5p, miR-30a-5p, miR-29b-3p, and miR-23a-3p also increased approximately 2-fold in AA, although not statistically significant. No significant differences were found in the screening of the remaining 35 miRNAs in patients with AA. CONCLUSION: Although there is little information about the relationship between AA and miRNAs currently, miR-29c-3p was reported to increase in the acute period of AA in this study. With the current results, it can be argued that miR-29c-3p bears the potential to be a marker in patients with AA. The present study may also be a basic research for more extensive and necessary miRNAs screening in this field. PMID- 29786816 TI - Examination of morbidity and mortality of cases according to intra-vehicle position and accident mechanism. AB - BACKGROUND: Traffic accidents are still an important public health issue in our country and intra-vehicle accidents cause substantial morbidity and mortality. In this study, we aimed to investigate the effect of seating position on morbidity and mortality in traffic accidents. METHODS: Patients who were admitted to the Emergency Department, Faculty of Medicine, Ege University between May 1, 2014 and November 30, 2014 due to injuries in motor vehicles and who signed informed consent were included. RESULTS: In total, 519 cases were included, and 329 (63.4%) were male and 190 (36.6%) were female. The average age was 33.11+/-16.86 (range, 0-85) years. It was noted that the accidents most frequently occurred between 18.00 and 23.59 (36.3%) hours, in the car (79%), and due to collision with another car (61.7%). Although 39.5% of the injured individuals were drivers, 26.4% were front seat passengers. From a forensic medicine perspective, life threatening injuries were approximately twice more common (37.5%-13.6%) in accidents with >110 km/h speed compared with accidents with <110 km/h speed. Accidents with >110 km/h speed caused approximately twice the amount (56.3% 26.3%) of injuries that cannot be resolved with simple medical intervention compared with accidents with <110 km/h speed. CONCLUSION: Since most people who are injured or die in traffic accidents have an active professional life, significant rehabilitation expenditure and labor loss occur along with diagnosis and treatment costs. Our study and similar studies not only show the effectiveness of the measures taken but also provide an insight into changing injury profiles and precautions to prevent them. PMID- 29786817 TI - Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients. AB - BACKGROUND: We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. METHODS: Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. RESULTS: A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. CONCLUSION: Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates. PMID- 29786818 TI - Management of traumatic arteriovenous fistulas: A tertiary academic center experience. AB - BACKGROUND: To present the surgical experience at a tertiary academic center of treating patients with traumatic arteriovenous fistulas (AVFs) who in whom endovascular treatment was contraindicated or in whom unsuccessful endovascular treatment had been performed. METHODS: A total of 27 patients with traumatic AVFs who underwent surgery between September 2014 and May 2016 were included. The site of injury, timing of surgery, and the surgical methods utilized were analyzed retrospectively. RESULTS: Arteriovenous fistulas were located in the lower extremity in 26 patients (96.29%) and in the upper extremity in one patient (3.7%). Etiological factors included gunshot injuries in 23 patients (85.18%) and penetrating injury in four patients (14.81%). AVFs in the lower extremity were between the popliteal artery and vein in 21 patients and between the femoral artery and vein in five patients. The one patient with upper-extremity AVF had a communication between the brachial artery and cephalic vein. Primary repair of the artery and vein after ligation, arterial graft interposition plus primary vein repair, and arterial and venous graft interposition were performed for surgical repair in two, five, and 20 patients, respectively. The saphenous vein was used for grafting in all cases needing grafts. CONCLUSION: In patients enduring penetrating trauma in the close vicinity of major vascular structures, a detailed history-taking and physical examination should be performed along with auscultation. The endovascular approach may represent the initial choice of management because of its lower rate of complications, noninvasive nature, decreased in-hospital costs, and decreased loss of work productivity. However, surgery is still unavoidable option in a significant proportion of patients who are either hemodynamically unstable, contraindicated for endovascular treatment, or in whom endovascular treatment was unsuccessful. PMID- 29786819 TI - Evaluation of pterygoid plate fractures unrelated to Le Fort fractures using maxillofacial computed tomography. AB - BACKGROUND: This study aims to describe the major pterygoid plate fractures (PPFs) patterns unrelated to Le Fort fractures (LFFs) using maxillofacial computed tomography (CT). METHODS: After obtaining our hospital ethics committee approval (37-05), data for PPF were acquired from the medical records of all the trauma patients who were diagnosed using CT at our hospital from April 2014 to April 2017. RESULTS: Of the 178 patients, 135 (male/female = 86/49; mean age = 37.2 years) had LFF and 43 (male/female = 35/8; mean age = 38.6 years) had PPF without associated LFF. PPF patterns unrelated to LFF included temporal bone (11.6%), sphenotemporal buttress (25.5%), zygomaticomaxillary complex (30.2%), displaced mandible (23.3%), nasal (4.7%), and isolated fractures (4.7%). The etiologies of facial fractures were not significantly different between both sexes (p=0.576). No significant difference between Le Fort and non-Le Fort groups was found for age (p=0.603) and the causes of trauma (p=0.183). CONCLUSION: PPF is most commonly seen with LFF, but it may also be seen alone or with other non LFF indicating that all PPF are not related to LFF. Axial reformatted CT images can easily display PPF and the degree of displacement of the fragments, and they can be used to guide surgical reduction of the fractures. PMID- 29786820 TI - Determination of trace element levels in patients with burst fractures. AB - BACKGROUND: This study aimed to determine trace element levels (Zn, Fe, Mn, Mg, Cu, Cd, Co, and Pb) in patients with burst fractures in Van Province, Turkey. METHODS: The study included a total of 44 participants with no additional pathologies, including 22 patients with burst fractures aged over 18 years who were admitted to the neurosurgery departments at two hospitals between June 15, 2015 and January 20, 2016 and 22 healthy volunteers. Serum samples were obtained from all participants to measure the serum levels of trace and heavy elements, including Mn, Cd, Cu, Pb, Fe, Co and Zn, using atomic absorbance spectrophotometry. RESULTS: The trace element levels of Zn, Mn, Cu, Co, and Mg were significantly lower (p<0.001), whereas those of Fe, Cd, and Pb were significantly higher in the patient group than in the control group. In addition, the levels of Zn, Mn, Cu, Co, and Mg were lower and the levels of Fe, Cd, and Pb were higher in the patient group than in the control group. CONCLUSION: The probability of burst fracture and its causes leading to any injury may be considered as an indicator balance for the concentration of trace elements between the patient group and control group and may also be a risk factor associated with the bone exposed to burst fracture Significant changes in serum levels of Zn, Cd, Mn, Mg, Pb, Fe, Cu and Zn elements can be observed in patients with burst fractures. PMID- 29786821 TI - Cardiac findings of sternal fractures due to thoracic trauma: A five-year retrospective study. AB - BACKGROUND: This study mainly aimed to determine the frequency of sternal fractures in thoracic trauma patients and to assess the differences in surgical need, cardiac findings, and treatment processes between patients with fracture on different sternal zones and displaced and non-displaced sternal fractures. METHODS: We analyzed the data of patients with sternal fracture due to thoracic trauma admitted to a state hospital between January 2011 and December 2015. Patient data comprised demographics, trauma characteristics, clinical findings, and treatment process. RESULTS: Of the 2764 thoracic trauma patients admitted during the study period, 72 (2.6%) had sternal fracture. The median age was 52 (inter quartile range: 61-38) years; the patients were predominantly male (F/M: 18/54). The most common causes of sternal fractures were motor vehicle accident, fall, and work accident. Of all the patients, 15 had displaced fracture. Abnormal echocardiogram findings were significantly more frequent in patients having fractures on the manubrium than in those having fractures on the corpus of the sternum. Patients who had fracture on the corpus had significantly lesser surgery need than those who had fracture on the manubrium of the sternum. Also, there was statistically significant difference between displaced and non-displaced sternal fracture cases in terms of surgery need (p<0.005). CONCLUSION: Abnormal echocardiography findings were more frequent in patients with sternal fracture on the manubrium and displaced fracture. PMID- 29786822 TI - Volar locking plate versus K-wire-supported external fixation in the treatment of AO/ASIF type C distal radius fractures: A comparison of functional and radiological outcomes. AB - BACKGROUND: The aim of this study was to compare the functional and radiological outcomes of K-wire-supported bridging external fixation (KW-EF) and volar locking plate (VLP) in the treatment of comminuted intra-articular distal radius fractures. METHODS: Patients treated for complex intra-articular distal radius fractures between February 2010 and April 2013 were retrospectively investigated. A total of 114 patients (42 females and 72 males) with a mean age of 44.9+/-15.4 (range: 18-86) years were evaluated. Wrist ranges of motion were measured using a universal goniometer, and hand grip strength was determined using hand dynamometers. The results were evaluated with Gartland-Werley score. QuickDASH questionnaire was administered in subjective functional assessment. Radiological evaluations were performed, with wrist radiographs obtained on the 3rd month and 2nd year. RESULTS: Wrist flexion, extension, pronation, and supination were all significantly better in the VLP group than in the KW-EF group at last control (p=0.001). Gartland-Werley, QuickDASH, and Visual Analog Scale were significantly better in the VLP than group than in the KW-EF group (p=0.003, p=0.003, and p=0.001, respectively). At the last follow-up, loss of grip strength compared with that on the uninjured side was 4% in the VLP group and 7% in the KW-EF group. CONCLUSION: VLP is a safe method with low complication rates. It is superior to KW-EF as it facilitates early return to daily activities and shows better functional and radiological outcomes in the 2nd year of treatment. PMID- 29786823 TI - Application of hybrid external fixation by the "joystick method" in bicondylar tibial plateau fractures: Technical note. AB - BACKGROUND: This study aimed to present clinical outcomes in patients with tibial plateau fractures who were treated with hybrid external fixators and describe the details of our technique. Schanz screws were synchronously applied and used as a joystick for fracture reduction. METHODS: The study population included 72 patients with bicondylar tibial plateau fractures classified as type 41-C2 according to the AO classification. Joint reduction was maintained using Schanz screws transmitted through tibial condyles as a joystick under fluoroscopy. The patients then underwent surgery with these Schanz screws and a hybrid external fixation system. RESULTS: The median age of the patients was 39 (21-67) years, and the median follow-up time was 21 (12-35) months. The mean knee flexion and extension were 105 degrees (80 degrees -125 degrees ) and 0 degrees (-5 degrees -7 degrees ), respectively. The mean varus laxity and valgus laxity were 4.30 degrees (2 degrees -7 degrees ) and 3.10 degrees (2 degrees -5 degrees ), respectively. Four patients had leg shortness of 0.4-1.1 cm. The external fixators were removed between 8 and 16 weeks (mean = 11 weeks) postoperatively. The KSS scores at the end of 1 year were "excellent" for 48 patients, "good" for 19 patients, and "inadequate" for 5 patients. CONCLUSION: With the synchronous application of the two Schanz screws of 6.5-mm thickness and the two-drill technique under fluoroscopic guidance, we obtained stable reductions over a short period. No patient experienced major complications, and this enabled early weight bearing and a return to daily living activities. PMID- 29786824 TI - Intramedullary nail with integrated cephalocervical screws in the intertrochanteric fractures treatment: Position of screws in fracture stability. AB - BACKGROUND: Stable fracture fixation is important in the treatment of intertrochanteric femur (ITF) fractures in the elderly population to prevent the loss of reduction, achieve early mobility, and restore independence. The aim of this study was to present the results of surgical treatment of stable and unstable ITF fractures using a trochanteric antegrade intramedullary nail with two cephalocervical screws in an integrated mechanism (Intertan(r); Smith & Nephew, Memphis, TN) and evaluate the relationship between the loss of reduction and screw position in the femoral neck in two planes. METHODS: The authors investigated all varus misalignments and losses of reduction in 57 patients (22 males, 35 females) treated for ITF fractures with the Intertan(r) between 2010 and 2011. Two indices (screw alignment index in the frontal projection [SAIcoronal] and screw alignment index in the lateral projection [SAIsagittal]) were defined to evaluate the loss of reduction. Patients were also evaluated according to the Harris hip score and Barthel independence index. RESULTS: The mean patient age was 77.1 years. The mean follow-up period was 21.7 months. All patients achieved complete union. We did not detect any varus collapse or loss of reduction. At the end of the follow-up period, the mean Barthel independence index was 90.7, and the mean Harris hip score was 83.7. CONCLUSION: The use of a trochanteric antegrade intramedullary nail with two cephalocervical screws allows for linear intraoperative compression and rotational stability of the head/neck fragment, prevents reduction loss, and has a wide application area in the femoral head. Its inherent continuous stability permits early weight-bearing and mobilization. It is a safe and an efficient option for the treatment of ITF fractures. PMID- 29786825 TI - The comparison of arthroscopic acromioplasty with and without acromioclavicular coplaning. AB - BACKGROUND: Coplaning means the removal of medial acromial spurs and inferior aspect of the distal clavicle. The aim of the study was to evaluate the outcomes of arthroscopic acromioplasty with and without coplaning in patients without acromioclavicular (AC) joint arthritis. METHODS: Because of impingement syndrome, arthroscopic subacromial decompression and acromioplasty was performed in Group 1 (9 males/31 female). In addition, coplaning was performed in Group 2 (8 males/21 females) by two different surgeons. The mean age was 48 in Group 1, 46 in Group 2. The mean follow-up was 50 months and 44 months, respectively. RESULTS: Constant score, cross-body adduction test and AC joint tenderness was used for follow-up. The mean preoperative Constant scores were 45 points (range: 34-76 points) in Group 1, 39 points (range: 32-69 points) in Group 2. The mean Constant scores at the latest follow-up was 78 points (range: 68-100 points) for Group 1, 84 points (range: 72-100 points) for Group 2. There was no statistically difference between two groups at the latest follow-up (p<0.05). In two patients in Group 2, cross-body adduction test was positive but asymptomatic. CONCLUSION: Excision of the inferior side of the lateral clavicle to the level of the acromion with minimal disruption of the joint capsule does not develop AC joint symptoms in long-term follow-up. PMID- 29786826 TI - Rare case of bilateral incarcerated obturator hernia: a case report. AB - Here, we report the case of an 84-year-old woman with acute mechanical intestinal obstruction (AMIO) who was admitted to our Emergency Department. Computed tomography (CT) scan revealed an incarcerated bilateral obturator hernia, and the defect was resolved using transabdominal preperitoneal (TAPP) technique with polypropylene mesh. The patient was administered an oral regimen two days after the operation. The patient stayed in the intensive care unit for 4 days and was uneventfully discharged on the 9th postoperative day. Follow-up was scheduled at the 6th month, during which no adverse events were detected and the patient did not report any complaints. Obturator hernia is among the differential diagnoses of intestinal obstruction requiring early diagnosis and prompt surgical intervention. Laparoscopic approach is less invasive compared with open surgery, and it can be attempted in cases presenting with no sign of ischemia or peritonitis. TAPP technique should be preferred since it allows the control of all intraabdominal pathologies and the viability of the intestines. PMID- 29786827 TI - The protective effect of Montelukast against skeletal muscle ischemia reperfusion injury: An experimental rat model. AB - BACKGROUND: Montelukast is a selective leukotriene D-4 receptor antagonist, which specifically and reversibly inhibits cysteinyl leukotriene-1 receptor. The aim of this study was to investigate the protective effect of Montelukast on skeletal muscle reperfusion injury created as acute ischemia-reperfusion (IR) injury in Wistar-albino rats. METHODS: The study comprised 16 male Wistar-albino rats. The rats were randomly separated into two groups as control (IR) and treatment (IR+Montelukast). Ischemia was obtained using a femoral artery clamp. After reperfusion following a 2-hour ischemia, muscle samples were taken for biochemical and histopathological analyses. RESULTS: Malondialdehyde levels were determined to be at statistically higher levels in the control compared with that in the Montelukast group (p=0.002, p<0.01). The superoxide dismutase levels were determined to be at statistically higher level in the Montelukast group compared with that in the control group (p=0.001, p<0.01). In the histopathological examination of the ischemic muscles, edema, polymorinfiltration and erythrocyte extravasation levels were found to be statistically significant higher in the control group than in the Montelukast group. Edema, polymorphonuclear infiltration, and erythrocyte extravasation levels were observed to be significantly reduced in the treatment group compared with that in the control. CONCLUSION: In this model of skeletal muscle acute IR injury, the protective effect of Montelukast against skeletal muscle reperfusion injury was emphasized. We concluded that Montelukast could accelerate functional recovery in the extremity by limiting the local and systemic complications caused by reperfusion in cases such as extremity trauma with vascular injuries and extremity surgery with prolonged tourniquet application. However, further experimental and clinical studies are required to confirm this effect. PMID- 29786828 TI - Oral contraceptives for pain associated with endometriosis. AB - BACKGROUND: Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The combined oral contraceptive pill (COCP) is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited. OBJECTIVES: To determine the effectiveness, safety and cost effectiveness of oral contraceptive preparations in the treatment of painful symptoms ascribed to the diagnosis of laparoscopically proven endometriosis. SEARCH METHODS: We searched the following from inception to 19 October 2017: the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane CENTRAL Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial registers ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform (WHO ICTRP). We also handsearched reference lists of relevant trials and systematic reviews retrieved by the search. SELECTION CRITERIA: We included randomised controlled trials (RCT) of the use of COCPs in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis that had been made visually at a surgical procedure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data. One review author was an expert in the content matter. We contacted study authors for additional information. The primary outcome was self-reported pain (dysmenorrhoea) at the end of treatment. MAIN RESULTS: Five trials (612 women) met the inclusion criteria. Only three trials (404 women) provided data that were suitable for analysis.Combined oral contraceptive pill versus placeboTwo trials compared COCP with a placebo. These studies were at high risk of bias. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence very low. Evidence was downgraded for imprecision as it was based on a single, small trial and for the visual analogue scale data there were wide confidence intervals (CIs). There appeared to have been substantial involvement of the pharmaceutical company funding the trials.Treatment with the COCP was associated with an improvement in self-reported pain at the end of treatment as evidenced by a lower score on the Dysmenorrhoea verbal rating scale (scale 0 to 3) compared with placebo (mean difference (MD) -1.30 points, 95% CI -1.84 to -0.76; 1 RCT, 96 women; very low quality evidence), a lower score on the Dysmenorrhoea visual analogue scale (no details of scale) compared with placebo (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women; very low quality evidence) and a reduction in menstrual pain from baseline to the end of treatment (MD 2.10 points, 95% CI 1.38 to 2.82; 1 RCT, 169 women; very low quality evidence).Combined oral contraceptive pill versus medical therapiesOne underpowered trial compared the COCP with another medical treatment (goserelin). The study was at high risk of bias; the trial was unblinded and there was insufficient detail to judge allocation concealment and randomisation. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence ranged from low to very low.At the end of treatment, the women in the goserelin group were amenorrhoeic and therefore no comparisons could be made between the groups for the primary outcome. At six months' follow-up, there was no clear evidence of a difference between women treated with the COCP and women treated with goserelin for measures of dysmenorrhoea on a visual analogue scale (scale 1 to 10) (MD -0.10, 95% CI -1.28 to 1.08; 1 RCT, 50 women; very low quality evidence) or a verbal rating scale (scale 0 to 3) (MD -0.10, 95% CI -0.99 to 0.79; 1 RCT, 50 women; very low quality evidence). At six months' follow-up, there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain as measured by the visual analogue scale (risk ratio (RR) 0.36, 95% CI 0.02 to 8.43; 1 RCT, 50 women; very low quality evidence) or the verbal rating scale (RR 1.00, 95% CI 0.93 to 1.08; 1 RCT, 49 women; low quality evidence). AUTHORS' CONCLUSIONS: Based on the limited evidence from two trials at high risk of bias and limited data for the prespecified outcomes for this review, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with placebo and the findings cannot be generalised.Based on the limited evidence from one small trial that was at high risk of bias, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with other medical treatments. Only one comparison was possible, with the medical intervention being goserelin, and the findings cannot be generalised.Further research is needed to fully evaluate the role of COCPs in managing pain-related symptoms associated with endometriosis. There are other formulations of the combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives which this review did not cover but should be considered in future updates. PMID- 29786829 TI - Meta-analysis examining the epidemiology of clozapine-associated neutropenia. AB - BACKGROUND: Clozapine is associated with life-threatening neutropenia. There are no previous meta-analyses of the epidemiology of clozapine-associated neutropenia. OBJECTIVES: To determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine. DATA SOURCES: A systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis]. METHODS: Random effects meta analysis to determine event rates and longitudinal incidence of events per 100 person-years of exposure. RESULTS: A total of 108 studies were included. The incidence of clozapine-associated neutropenia was 3.8% (95% CI: 2.7-5.2%) and severe neutropenia 0.9% (95% CI: 0.7-1.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01-0.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6-2.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment. CONCLUSION: Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine associated neutropenia is extremely rare. Implications for haematological monitoring are discussed. PMID- 29786831 TI - Response to: Revisiting the impact of red cell storage duration on adverse outcomes after transfusion. PMID- 29786830 TI - Blue-light filtering intraocular lenses (IOLs) for protecting macular health. AB - BACKGROUND: An intraocular lens (IOL) is a synthetic lens that is surgically implanted within the eye following removal of the crystalline lens, during cataract surgery. While all modern IOLs attenuate the transmission of ultra violet (UV) light, some IOLs, called blue-blocking or blue-light filtering IOLs, also reduce short-wavelength visible light transmission. The rationale for blue light filtering IOLs derives primarily from cell culture and animal studies, which suggest that short-wavelength visible light can induce retinal photoxicity. Blue-light filtering IOLs have been suggested to impart retinal protection and potentially prevent the development and progression of age-related macular degeneration (AMD). We sought to investigate the evidence relating to these suggested benefits of blue-light filtering IOLs, and to consider any potential adverse effects. OBJECTIVES: To assess the effects of blue-light filtering IOLs compared with non-blue-light filtering IOLs, with respect to providing protection to macular health and function. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 9); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 25 October 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs), involving adult participants undergoing cataract extraction, where a blue light filtering IOL was compared with an equivalent non-blue-light filtering IOL. DATA COLLECTION AND ANALYSIS: The prespecified primary outcome was the change in distance best-corrected visual acuity (BCVA), as a continuous outcome, between baseline and 12 months of follow-up. Prespecified secondary outcomes included postoperative contrast sensitivity, colour discrimination, macular pigment optical density (MPOD), proportion of eyes with a pathological finding at the macula (including, but not limited to the development or progression of AMD, or both), daytime alertness, reaction time and patient satisfaction. We evaluated findings related to ocular and systemic adverse effects.Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached a consensus on any disagreements by discussion. Where appropriate, we pooled data relating to outcomes and used random-effects or fixed-effect models for the meta analyses. We summarised the overall certainty of the evidence using GRADE. MAIN RESULTS: We included 51 RCTs from 17 different countries, although most studies either did not report relevant outcomes, or provided data in a format that could not be extracted. Together, the included studies considered the outcomes of IOL implantation in over 5000 eyes. The number of participants ranged from 13 to 300, and the follow-up period ranged from one month to five years. Only two of the studies had a trial registry record and no studies referred to a published protocol. We did not judge any of the studies to have a low risk of bias in all seven domains. We judged approximately two-thirds of the studies to have a high risk of bias in domains relating to 'blinding of participants and personnel' (performance bias) and 'blinding of outcome assessment' (detection bias).We found with moderate certainty, that distance BCVA with a blue-light filtering IOL, at six to 18 months postoperatively, and measured in logMAR, was not clearly different to distance BCVA with a non-blue-light filtering IOL (mean difference (MD) -0.01 logMAR, 95% confidence interval (CI) -0.03 to 0.02, P = 0.48; 2 studies, 131 eyes).There was very low-certainty evidence relating to any potential inter-intervention difference for the proportion of eyes that developed late-stage AMD at three years of follow-up, or any stage of AMD at one year of follow-up, as data derived from one trial and two trials respectively, and there were no events in either IOL intervention group, for either outcome. There was very low-certainty evidence for the outcome for the proportion of participants who lost 15 or more letters of distance BCVA at six months of follow-up; two trials that considered a total of 63 eyes reported no events, in either IOL intervention group.There were no relevant, combinable data available for outcomes relating to the effect on contrast sensitivity at six months, the proportion of eyes with a measurable loss of colour discrimination from baseline at six months, or the proportion of participants with adverse events with a probable causal link with the study interventions after six months.We were unable to draw reliable conclusions on the relative equivalence or superiority of blue-light filtering IOLs versus non-blue-light filtering IOLs in relation to longer-term effects on macular health. We were also not able to determine with any certainty whether blue-light filtering IOLs have any significant effects on MPOD, contrast sensitivity, colour discrimination, daytime alertness, reaction time or patient satisfaction, relative to non-blue-light filtering IOLs. AUTHORS' CONCLUSIONS: This systematic review shows with moderate certainty that there is no clinically meaningful difference in short-term BCVA with the two types of IOLs. Further, based upon available data, these findings suggest that there is no clinically meaningful difference in short-term contrast sensitivity with the two interventions, although there was a low level of certainty for this outcome due to a small number of included studies and their inherent risk of bias. Based upon current, best-available research evidence, it is unclear whether blue-light filtering IOLs preserve macular health or alter risks associated with the development and progression of AMD, or both. Further research is required to fully understand the effects of blue-light filtering IOLs for providing protection to macular health and function. PMID- 29786832 TI - The primary active components, antioxidant properties, and differential metabolite profiles of radish sprouts (Raphanus sativus L.) upon domestic storage: analysis of nutritional quality. AB - BACKGROUND: This study aimed to analyze the nutritional quality of radish sprouts (Raphanus sativus L.) after domestic short-term storage. We stored fresh radish sprouts at 25 +/- 1 degrees C and at 4 +/- 1 degrees C for 12 h, and detected phenolic substances, glucosinolates, isothiocyanates, vitamin C, and various antioxidant and abiotic stress-related factors. We investigated nutrient-related metabolic differences and associated pathways and postharvest treatment effects on nutritional quality using metabolomic analysis. RESULTS: Most active substances and antioxidant properties, but not phenolic acids and vitamin C, decreased significantly (P < 0.05) upon domestic storage; this reduction decelerated at low temperatures. Short-term storage disrupted redox balance; low temperature enhanced stress resistance. Differences were observed in amino acid and vitamin derivatives, phospholipid accumulation, and organic acids. Short-term storage at ambient temperature promoted lysine, threonine, cysteine, vitamin H, phospholipid, and lauric (dodecanoic) acid accumulation, inhibiting proline, phosphatidic acid (PA) (14:1(9Z)/12:0), and phosphatidylcholine (PC) (O-18:0/O 18:0) accumulation; low-temperature, short-term storage promoted myristic acid and phospholipid accumulation and reduced methionine synthesis and vitamin H and K accumulation. CONCLUSION: Overall, the nutritional quality of radish sprout decreased upon short-term storage, with differences in certain active substances. (c) 2018 Society of Chemical Industry. PMID- 29786833 TI - Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI. AB - INTRODUCTION: Cerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. As yet, we do not know whether the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty of examining the cerebral circulation. MATERIAL AND METHODS: We have used a non-invasive diffusion weighted-magnetic resonance imaging technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n = 30), normal pregnancy (n = 32), and non-pregnant women (n = 16). Estimates of cerebral blood volume, blood flow, and edema were measured in 5 different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and gray matter. RESULTS: Except for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus, we found lower cerebral blood volume and lower blood flow in preeclampsia than in either normal pregnancy (P = .01 and P = .03, respectively) or non-pregnant women (both P = .02). No differences in edema were detected between study groups. CONCLUSION: The cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia but not in normal pregnancy or non-pregnant women. PMID- 29786836 TI - Initiating life-long aerobic exercise 4-5 days per week before or near age 50 years: is this the 'holy-grail' of preventing age-related central artery stiffness? PMID- 29786834 TI - Assessment of lactate production as a response to sustained intrapartum hypoxia in large-for-gestational-age newborns. AB - INTRODUCTION: Lactate concentration in umbilical cord blood is an important measure of intrapartum anaerobic metabolism. The aim of the study was to compare lactate production of large-for-gestational-age (LGA) fetuses against appropriate for-gestational-age (AGA) fetuses during hypoxia, in diabetic and non-diabetic mothers. MATERIAL AND METHODS: A total of 17 358 validated paired arterial and venous umbilical cord blood samples taken at birth with a full panel of pH, glucose, and lactate were analyzed relative to LGA (n = 2789) and AGA (n = 14 569). Umbilical cord blood acidemia (pH < mean minus 2 SD) was identified in 518 cases. RESULTS: Diabetes, but not acidemia, was more common among LGA (5.4%) than AGA cases (2.9%) (respectively P < .0001 and P < .69). At normal pH, glucose was lower in non-diabetes LGA cases, but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .067). Glucose levels were higher in all groups during acidemia (P <= .0005), with lower values in non diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P = .005 and P < .58). At normal pH, lactate was lower in non diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .98); during acidemia, lactate levels were higher in all groups (P < .0001), resulting in no significant difference between LGA and AGA in diabetes as well as in non-diabetes cases (respectively P = .29 and P < .084). CONCLUSIONS: Considering cord acidemia a proxy for intrapartum hypoxia, LGA fetuses showed no impaired ability to produce lactate during hypoxia. Maternal diabetes did not hamper the ability of LGA fetuses to produce lactate during hypoxia. PMID- 29786835 TI - Bilateral asymmetry of the humerus in Neandertals, Australian aborigines and medieval humans. AB - OBJECTIVES: Bilateral asymmetry of diaphyseal shape and size may be a reflection of relative activity levels and patterns of habitual biomechanical stress in the upper arms of Neandertals and Homo sapiens. The main purpose of our study was to assess the level of directional asymmetry of humeral cross sections in Neandertals, recent Australian aborigines, and medieval farmers. MATERIALS AND METHODS: Indices of directional and absolute asymmetry (%DA and %AA) of humeral cross-sectional properties in Neandertals and recent Homo sapiens were calculated. Evenly distributed semilandmarks around the external and internal borders of cortical bone were digitized in the course of computed tomography for analysis of shape differences between sides of the body. RESULTS: The medieval farmers were characterized by significant %DA and %AA for polar second moment of area (J), ratio of maximum to minimum second moments of area, and ratio of antero posterior to medio-lateral bending strength. In Australian aborigines, only J in males shows significant %DA and %AA, while Neandertals exhibit no significant asymmetry of any cross-sectional properties. Differences in cross-sectional shape between sides of the body were established in all three analyzed groups. DISCUSSION: High levels of directional asymmetry of cross-sectional shape and properties in medieval farmers may be caused by the performance of more physically demanding tasks using one side of the body from an early age in that population. Various patterns of asymmetry in Neandertals and modern humans may be caused by different habitual behaviors during growth, eco-geographic patterns in body proportions, genetic factors, and differences in ontogeny. PMID- 29786837 TI - High Intensity Ultrasound for Salmonella Enteritidis Inactivation in Culture and Liquid Whole Eggs. AB - High intensity ultrasound (HIU) continues to be researched as a nonthermal inactivation technology of appeal to food manufacturers. The advantages of HIU include maintenance of product quality, freshness, product homogenization, along with simultaneous inactivation of pathogens. Besides, it is simple, relatively inexpensive, and easily adaptable to most processing environments. This study investigated the effect of HIU for Salmonella Enteritidis inactivation in culture and liquid whole eggs (LWEs) to decrease egg-associated outbreaks. Overnight S. Enteritidis cultures and spiked LWE (both at 8 log CFU/mL) were treated with 20 kHz HIU for 0, 1, 5, 10, and 30 min (n = 6) in a temperature-controlled system, not to exceed 20 degrees C, and replicated thrice. At each time point, samples were enumerated on XLT4 agar and morphologically analyzed using scanning electron microscopy, with measurements of color and rheological properties. Our results revealed significant reduction of healthy S. Enteritidis cells up to 3.6 log CFU/mL and 2.3 log CFU/25 mL after HIU treatment of merely 10 min of overnight culture and 30 min in LWE, respectively (P < 0.05). After 5 and 10-min HIU treatment, significant reduction of 1.4-log CFU/25 mL healthy S. Enteritidis in LWE was obtained (P < 0.05). Even at 1-min exposure time, HIU showed significant 1.9 log CFU/mL reduction of cultures (P < 0.05); however, no log-reduction was observed in LWE after 1 min. Scanning electron micrographs showed increased cell structural damage using longer HIU exposure. For product color changes, lower redness and yellowness of LWE were observed visually and instrumentally after 5 min HIU treatment (P < 0.05). The rheological properties of LWE measured at 0 to 200 s-1 shear rate, showed that shear stress of HIU-treated LWEs decreased after 5-min HIU exposure, but increased after 30-min treatment. This study demonstrated that HIU shows promise for rapid Salmonella control in LWE and other liquid foods, as an alternative inactivation method for use in hurdle approaches. PMID- 29786838 TI - Edible Gum-Phenolic-Lipid Incorporated Gluten Films for Food Packaging. AB - : The aim of this investigation was to improve the barrier and mechanical properties of gluten films and further explore their application in the packaging of seasonings. The effects of flaxseed gum (FG), oligomeric procyanidins (OPCs), and lauric acid (LA) on the water vapor permeability (WVP), mechanical properties, and peroxide value (POV) were determined. FG and OPCs improved the WVP properties of the gluten films, whereas LA significantly improved the oxygen barrier properties. The FG/OPCs/LA/GP composite film was then optimized, and the morphological, microstructural, and thermal properties of the composite gluten film were investigated by scanning electron microscopy, atomic force microscopy, surface hydrophobicity analysis; Fourier transform infrared spectroscopy; thermal gravimetric analysis, respectively. The results confirmed that gluten is compatible with FG, OPCs, and LA, thereby leading to the formation of a more uniform, dense, and hydrophobic film. The changes in the preservation properties (appearance, POV, and acid value) of the composite gluten film for oil, salt, and vegetable packaging were also examined. The composite gluten film maintained some degree of seasoning packaging capacity over a 75-day storage period, indicating its potential for uses as a packaging material for seasonings in food production. PRACTICAL APPLICATION: The edible composite film will be produced in industry according to the data provided in our paper; the film can be used as packaging material for seasonings in food production. PMID- 29786839 TI - The Influence of Scalded Flour, Fermentation, and Plants Belonging to Lamiaceae Family on the Wheat Bread Quality and Acrylamide Content. AB - : The aim of this study was to investigate the influence of additives such as plants belonging to Lamiaceae family (Thymus vulgaris, Carum carvi, Origanum vulgare, Ocimum basilicum, and Coriandrum sativum), scalded flour (SF) or scalded flour fermented with Lactobacillus plantarum LUHS135 (SFFLp) on the quality and acrylamide formation in wheat bread. The formation of acrylamide and bread quality significantly depended on the king of plants used and the amount of SF and SFFLp used. The additives of T. vulgaris and SF increased the content of acrylamide by 3.4-fold in comparison with bread prepared without SF, whereas the addition of SFFLp significantly reduced the content of acrylamide in bread, especially using 5% of SFFLp supplemented with O. vulgare and 15% of SFFLp supplemented with C. sativum (respectively by 40% and 29.4%) therefore could be recommended for safer bread production. PRACTICAL APPLICATION: The addition of 5% (from total wheat flour content) of scalded wheat flour fermented with Lactobacillus plantarum LUHS135 strain (SFFLp) with Origanum vulgare addition, and 5% or 10% of SFFLp prepared with Ocimum basilicum, and 15% of SFFLp prepared with Coriandrum sativum significantly reduce the content of acrylamide in wheat bread, therefore could be recommended for safer bread production. PMID- 29786840 TI - Spray-Drying of Milk-Blackberry Pulp Mixture: Effect of Carrier Agent on the Physical Properties of Powder, Water Sorption, and Glass Transition Temperature. AB - : Spray dryer was used to produce particles from a milk-blackberry pulp mixture (25%:75% (w/w)). Maltodextrin 10DE and 20DE and gum Arabic were used as adjuvants in order to improve powder quality. The particles were analyzed with emphasis on physical and physicochemical characteristics: moisture content, bulk density, particle size, morphology, water activity, anthocyanins retention, anthocyanins content, hygroscopicity, solubility, water sorption, and glass transition temperature. The best results were obtained for the paste composition of 25% concentrated milk-70% blackberry pulp-5% gum Arabic, yielding high anthocyanins retention (>87.5%), low powder moisture content of 0.0265 g H2 O/g dry matter and a higher powder solubility (>71.8%) when compared with other formulations. The increase of water content led to a decrease of powder's glass transition temperature. Powder stability was evaluated and the critical values of relative humidity and moisture content were estimated based on state diagrams of glass transition combined with sorption isotherm data. PRACTICAL APPLICATION: The growing interest in blackberries is due to the presence of anthocyanins which have shown possible application as a natural dye for food and pharmaceutical products. Drying a mixture of blackberry pulp and milk may produce particles with a broad range of intrinsic nutrients. Milk components could act as a wall material and emulsifying agent, protecting the flavonoids from blackberry. Therefore, a milk-blackberry powder becomes an alternative, which may reduce postharvesting waste and increase the shelf life of the product without significantly altering its nutritional characteristics. PMID- 29786841 TI - Development of a Chlorine Dosing Strategy for Fresh Produce Washing Process to Maintain Microbial Food Safety and Minimize Residual Chlorine. AB - : The residual free chlorine level in fresh produce wash solution is closely correlated to the chemical and microbial safety of produce. Excess amount of free chlorine can quickly react with organic matters to form hazardous disinfection by products (DBPs) above EPA-permitted levels, whereas deficiency of residual chlorine in produce wash solution may result in incompletely removing pathogens on produce. The purpose of this study was to develop a chlorine dosing strategy to optimize the chlorine dosage during produce washing process without impacting the microbial safety of fresh produce. Prediction equations were developed to estimate free chlorine needed to reach targeted residual chlorine at various sanitizer pH and organic loads, and then validated using fresh-cut iceberg lettuce and whole strawberries in an automated produce washer. Validation results showed that equations successfully predicted the initial chlorine concentration needed to achieve residual chlorine at 10, 30, 60, and 90 mg/L for both lettuce and strawberry washing processes, with the root mean squared error at 4.45 mg/L. The Escherichia coli O157:H7 reductions only slightly increased on iceberg lettuce and strawberries with residual chlorine increasing from 10 to 90 mg/L, indicating that lowering residual chlorine to 10 mg/L would not compromise the antimicrobial efficacy of chlorine-based sanitizer. Based on the prediction equations and E. coli O157:H7 reduction results, a chlorine dosing strategy was developed to help the produce industry to maintain microbial inactivation efficacy without adding excess amount of free chlorine. PRACTICAL APPLICATION: The chlorine dosing strategy can be used for fresh produce washing process to enhance the microbial food safety and minimize the DBPs formation potential. PMID- 29786842 TI - Correlated time-variation of bulk microstructure and rheology in asphalt binders. AB - We use near-infrared dark-field optical microscopy to probe isothermal time variation of the volume fraction of naturally-occurring, subsurface microstructures in PG 64-22 asphalt binders at temperature T=30?C, following a rapid heating (cooling) increment |DeltaT|=20?C from initial temperature T0=10?C(50?C). We compare these microstructure variations with isothermal time variations of the magnitude |G30*(t)| of the bulk complex shear modulus measured for identical sample conditions with a Dynamic Shear Rheometer. The main findings are: (1) Microstructure volume fraction (inferred from intensity I(t) of near infrared optical scatter) and |G*(t)| both continue to change appreciably long after measurable changes of binder temperature cease. Moreover, delayed time variations in I(t) and |G*(t)| (2) correlate closely with each other; (3) evolve on three distinct time scales - several minutes, ~1 h, >1 day; (4) depend on binder aging; (5) are more pronounced after a cooling step (DeltaT=-20?C) than after a heating step (DeltaT=+20?C); and (6) account for hysteresis in I(t) and |G*(t)| curves observed during heating-cooling cycles. PMID- 29786843 TI - Effect of Canning and Freezing on the Nutritional Content of Apricots. AB - : The effect of commercial canning and freezing on the nutritional content of fresh apricots was investigated. Processed samples were analyzed post-processing and after 3 months of storage and compared directly to fresh apricots from the same source. Vitamin C, beta-carotene, total phenols, and antioxidants were quantified. Compared to fresh, canned apricots initially exhibited similar levels of antioxidants, a 17% increase in beta-carotene, and a 48% increase in phenols, while vitamin C was reduced by 37%. After 3 months of storage, antioxidant levels were 47% higher than fresh. Vitamin C did not change significantly following storage and beta-carotene decreased by 15%. The canned apricot fruit packed in light syrup did not have higher total soluble solids (TSS) levels indicating no increase in fruit sugar content. Frozen apricots exhibited large increases in antioxidants (529%), beta-carotene (35%), vitamin C (3,370%), and phenols (406%) compared to fresh. After 3 months of storage, frozen apricots decreased in vitamin C (29%) and phenols (17%), but remained 2,375% and 318% higher than fresh, respectively. Beta-carotene increased during storage, reaching levels 56% higher than fresh while antioxidant activity was unchanged. This study demonstrates that key nutrients in canned and frozen apricots are retained or amplified upon processing, with the exception of vitamin C in canned apricots. The routine addition of citric and ascorbic acid to fruit prior to freezing resulted in significantly higher antioxidants, vitamin C, and phenols. Consumers eating canned or frozen apricots can feel confident of similar or superior nutritional content as compared to fresh apricots. PRACTICAL APPLICATION: The apricot industry is limited by the short shelf life of the fruit and consumer belief that processed produce is not as nutritious as fresh. Assessing the nutritional content of canned and frozen apricots and determining that processed apricots can deliver nearly comparable nutrient levels to fresh apricots provides the evidence needed to dispel these misconceptions and potentially increase demand for processed apricots among consumers. PMID- 29786844 TI - Effect of Meat Type, Animal Fatty Acid Composition, and Isothermal Temperature on the Viscoelastic Properties of Meat Batters. AB - : The aim of this research was to simultaneously study the effect of meat type (chicken breast and leg meat), animal fatty acid composition (selected pork backfats having a low and high degree of saturation, respectively), and isothermal temperature (50, 60, 70, and 80 degrees C) on the viscoelastic properties of meat batters during and after application of different time temperature profiles. Gelation of meat proteins contributed most to the viscoelastic properties of meat batters during heating, whereas crystallization of the lipids especially contributed to the viscoelastic properties during the cooling phase. Although the meat type had little effect on the final viscoelastic properties of the meat product, the fatty acid composition had a clear impact on the melting peak area (and therefore solid fat content) of lard, and subsequently on the final viscoelastic properties of meat batters prepared with different types of fats, with higher G' (elastic modulus) values for the most saturated animal fat. The crystallization of the fat clearly transcended the effect of the meat type with regard to G' at the end of the process. With increasing (isothermal) temperature, G' of meat batters increased. Therefore, it could be concluded that the structural properties of heated meat batters mainly depend on the heating temperature and the fatty acid composition, rather than the meat type. PRACTICAL APPLICATION: Quality characteristics of cooked sausages depend on multiple factors such as the meat and fat type, non-meat ingredients and processing conditions. From this study it could be concluded that the structural properties of cooked sausage batters mainly depend on the heating temperature and the fatty acid composition, rather than the meat type. Because the fatty acid composition of different animal fats differs widely, these results may be a concern for all manufactures of cooked sausages products with regard to the product structure and final texture, keeping in mind that rendered fat was used in this study, which is not common in sausage making. PMID- 29786846 TI - The pendulum swings back: Screening for prostate cancer in 2018. PMID- 29786845 TI - A Simple and Portable Screening Method for Adulterated Olive Oils Using the Hand Held FTIR Spectrometer and Chemometrics Tools. AB - : Extra virgin olive oil has been one of the most common targets for economically motivated food adulteration. This research employed the hand-held FTIR spectrometer to develop the simple and portable screening methods for extra virgin olive oils adulterated with other cheaper vegetable oils. With the help of the ATR probe and chemometrics tools, oil samples can be measured directly without any pretreatment, then the spectra can be interpreted automatically to determine the possibility of adulteration and estimate the content of adulterant oil. A feasibility study of the hand-held FTIR screening method was carried out using olive oils adulterated with canola oil, peanut oil, corn oil, soybean oil, and sunflower oil. The SIMCA model using the hand-held FTIR spectra can identify different kinds of vegetable oils correctly and recognize olive oils with not less than 10% of adulterant oils. Meanwhile, the content of adulterant oil in the range of 5% to 45% can be estimated by the PLS model using the hand-held FTIR spectra within an error of 3%. This research shows the potential of the hand-held FTIR technique in the rapid and field screening of olive oils adulterated with some cheaper vegetable oils. PRACTICAL APPLICATION: This research provide a rapid and automatic detection method for olive oils adulterated with other cheaper vegetable oils. An oil sample can be measured directly within one minute, and the hand-held instrument can be used anywhere needed. PMID- 29786847 TI - Assessment of Antibiotic Susceptibility within Lactic Acid Bacteria and Coagulase Negative Staphylococci Isolated from Hunan Smoked Pork, a Naturally Fermented Meat Product in China. AB - : The aim of this study was to evaluate the antibiotic susceptibility of lactic acid bacteria (LAB) and coagulase-negative staphylococci (CNS) strains isolated from naturally fermented smoked pork produced in Hunan, China. A total of 48 strains were isolated by selective medium and identified at the species level by 16S rRNA gene sequencing as follows: Staphylococcus carnosus (23), Lactobacillus plantarum (12), Lactobacillus brevis (10), Lactobacillus sakei (1), Weissella confusa (1), and Weissella cibaria (1). All strains were typed by RAPD-PCR, and their susceptibility to 15 antibiotics was determined and expressed as the minimum inhibitory concentration (MIC) using agar dilution method. High resistance to penicillin G, streptomycin, gentamycin, vancomycin, chloramphenicol, norfloxacin, ciprofloxacin, kanamycin, and neomycin was found among the isolates. All the strains were sensitive to ampicillin, while the susceptibility to tetracycline, oxytetracycline, erythromycin, lincomycin, and roxithromycin varied. The presence of relevant resistance genes was investigated by PCR and sequencing, with the following genes detected: str(A), str(B), tet(O), tet(M), ere(A), and catA. Eleven strains, including 3 S. carnosus, 6 L. plantarum, and 2 L. brevis, harbored more than 3 antibiotic resistance genes. Overall, multiple antibiotic resistance patterns were widely observed in LAB and S. carnosus strains isolated from Hunan smoked pork. Risk assessment should be carried out with regard to the safe use of LAB and CNS in food production. PRACTICAL APPLICATION: We evaluated the antibiotic resistance of lactic acid bacteria and coagulase-negative staphylococci strains isolated from Chinese naturally fermented smoked pork. Our results may provide important data on establishing breakpoint standards for LAB and CNS and evaluating the safety risk of these strains for commercial use. PMID- 29786848 TI - Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics. AB - BACKGROUND: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS: Incidence data were obtained from the CDC-funded and NCI-funded population-based cancer registry programs and compiled by NAACCR. Data on cancer deaths were obtained from the National Center for Health Statistics National Vital Statistics System. Trends in age-standardized incidence and death rates for all cancers combined and for the leading cancer types by sex, race, and ethnicity were estimated by joinpoint analysis and expressed as the annual percent change. Stage distribution and 5-year survival by stage at diagnosis were calculated for breast cancer, colon and rectum (colorectal) cancer, lung and bronchus cancer, and melanoma of the skin. RESULTS: Overall cancer incidence rates from 2008 to 2014 decreased by 2.2% per year among men but were stable among women. Overall cancer death rates from 1999 to 2015 decreased by 1.8% per year among men and by 1.4% per year among women. Among men, incidence rates during the most recent 5-year period (2010 2014) decreased for 7 of the 17 most common cancer types, and death rates (2011 2015) decreased for 11 of the 18 most common types. Among women, incidence rates declined for 7 of the 18 most common cancers, and death rates declined for 14 of the 20 most common cancers. Death rates decreased for cancer sites, including lung and bronchus (men and women), colorectal (men and women), female breast, and prostate. Death rates increased for cancers of the liver (men and women); pancreas (men and women); brain and other nervous system (men and women); oral cavity and pharynx (men only); soft tissue, including heart (men only); nonmelanoma skin (men only); and uterus. Incidence and death rates were higher among men than among women for all racial and ethnic groups. For all cancer sites combined, black men and white women had the highest incidence rates compared with other racial groups, and black men and black women had the highest death rates compared with other racial groups. Non-Hispanic men and women had higher incidence and mortality rates than those of Hispanic ethnicity. Five-year survival for cases diagnosed from 2007 through 2013 ranged from 100% (stage I) to 26.5% (stage IV) for female breast cancer, from 88.1% (stage I) to 12.6% (stage IV) for colorectal cancer, from 55.1% (stage I) to 4.2% (stage IV) for lung and bronchus cancer, and from 99.5% (stage I) to 16% (stage IV) for melanoma of the skin. Among children, overall cancer incidence rates increased by 0.8% per year from 2010 to 2014, and overall cancer death rates decreased by 1.5% per year from 2011 to 2015. CONCLUSIONS: For all cancer sites combined, cancer incidence rates decreased among men but were stable among women. Overall, there continue to be significant declines in cancer death rates among both men and women. Differences in rates and trends by race and ethnic group remain. Progress in reducing cancer mortality has not occurred for all sites. Examining stage distribution and 5-year survival by stage highlights the potential benefits associated with early detection and treatment. Cancer 2018;124:2785-2800. (c) 2018 American Cancer Society. PMID- 29786849 TI - Isolation and Characterization of Wheat Derived Nonspecific Lipid Transfer Protein 2 (nsLTP2). AB - Numerous studies support the protective role of bioactive peptides against cardiovascular diseases. Cereals represent the primary source of carbohydrates, but they also contain substantial amounts of proteins, therefore representing a potential dietary source of bioactive peptides with nutraceutical activities. The analysis of wheat extracts purified by chromatographic techniques by means of HPLC-UV/nanoLC-nanoESI-QTOF allowed the identification of a signal of about 7 kDa which, following data base searches, was ascribed to a nonspecific lipid-transfer protein (nsLTP) type 2 from Triticum aestivum (sequence coverage of 92%). For the first time nsLTP2 biological activities have been investigated. In particular, in experiments with human umbilical vein endothelial cells (HUVEC), nsLTP2 displayed antioxidant and cytoprotective activities, being able to significantly decrease reactive oxygen species (ROS) levels and to reduce lactate dehydrogenase (LDH) release, generated following oxidative (hydrogen peroxide) and inflammatory (tumor necrosis factor alpha, interleukin-1beta, and lipopolysaccharide) stimulation. The obtained promising results suggest potential protective role of nsLTP2 in vascular diseases prevention. PRACTICAL APPLICATION: nsLTP 2 peptide is resistant to proteases throughout the gastrointestinal tract and exerts antioxidant and cytoprotective activities. These characteristics could be exploited in vascular diseases prevention. PMID- 29786850 TI - Plasticizers and BPA Residues in Tunisian and Italian Culinary Herbs and Spices. AB - : In the present study, 18 plasticizers and residues in 10 different Tunisian and Italian culinary herbs and spices (black pepper, mint, caraway, coriander, oregano, rosemary, thyme, fennel, verbena, and laurel) were determined by GC/MS. Di-methylphthalate, di-(2-methylpropyl)adipate, di-n-butyladipate, di propylphthalate, benzylbenzoate, di-phenylphthalate, and bisphenol A were lower than their LOQ in all 118 samples. Among the Tunisian samples, di-(2 ethylhexyl)phthalate was found in all types of samples and di-butylphthalate in 50% of types; all other phthalates were rarely dectected. Among the adipates, only di-methyladipate was found in 90% of types; di-ethyladipate was seldom found and di-(2-ethylhexyl)adipate only in samples of caraway. Di-(2 ethylhexyl)terephthalate was found in all types of samples; di-(2 ethylhexyl)sebacate was detected rarely but with high values. Among the Sicilian samples, di-ethylphthalate and di-(2-methylpropyl)phthalate were detected only in samples of mint; di-methyladipate, di-butylphthalate, and benzylbutylphthalate were identified in oregano and laurel; di-(2-ethylhexyl)terephthalate and di-(2 ethylhexyl)sebacate only in oregano. In any case, the results suggested that intake of these contaminants through spices and herbs is not a dangerous risk to the consumers. Probably, as already observed for the other food, these contaminants could result from pollution of the environment (air, water, and/or soil) and/or farming methods. PRACTICAL APPLICATION: Plasticizers and BPA in Tunisian and Italian spices were determined by GC/MS. Tunisian spices seem to contain more residues than Italian samples. Intake of these contaminants by spices is not a dangerous risk to the consumers. These pollutants could result from environmental pollution or agricultural practices. PMID- 29786851 TI - Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics. AB - BACKGROUND: Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates. METHODS: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension. In addition, the analysis included trends for prostate cancer mortality between 1975 and 2015 by race and the estimation of PSA testing prevalence between 1987 and 2005. The annual percent change was calculated for periods defined by significant trend change points. RESULTS: For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from 2007. However, the incidence of distant-stage disease increased from 2010 to 2014. The incidence of disease according to higher PSA levels or Gleason scores at diagnosis did not increase. After years of significant decline (from 1993 to 2013), the overall prostate cancer mortality trend stabilized from 2013 to 2015. CONCLUSIONS: After a decline in PSA test usage, there has been an increased burden of late-stage disease, and the decline in prostate cancer mortality has leveled off. Cancer 2018;124:2801-2814. (c) 2018 American Cancer Society. PMID- 29786852 TI - Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy. AB - OBJECTIVE: We analyzed long-term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy. METHODS: Forty-one children (25 males) with drug-resistant epilepsy had a baseline positron emission tomography (PET) scan at a median age of 4.7 years; the scans were repeated after a median of 4.3 years. Children with progressive neurological disorders or space-occupying lesion-related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2-deoxy-2(18 F)-fluoro-D-glucose-PET at baseline and follow-up was correlated with epilepsy variables and developmental outcome. RESULTS: On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow-up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow-up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline (r = .31, P = .05) and follow-up scans (r = .27, P = .09). SIGNIFICANCE: In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered. PMID- 29786853 TI - Cysteamine-Modified Gold Nanoparticles as a Colorimetric Sensor for the Rapid Detection of Gentamicin. AB - : A simple, rapid, and specific colorimetric method for gentamicin detection using cysteamine-modified gold nanoparticles (cys-AuNPs) has been developed. The maximum residue limits of gentamicin allowed in foods are typically below 100 nM, so an effective detection method for low concentrations of the drug is required. The aggregation of gold nanoparticles (AuNPs) was used as the basis for this method, and adding cysteamine to the AuNPs helped to enhance their aggregative abilities. The cys-AuNPs are capable of detecting gentamicin concentrations as low as 12.45 nM in water, which could be quantified using UV-vis spectroscopy. Samples extracted from skim milk with a simple pretreatment showed that gentamicin concentrations down to at least 100 nM could be observed using the cys AuNPs. This study demonstrates the ability of the cys-AuNPs to rapidly detect and quantify gentamicin in both simple and complex matrices. PRACTICAL APPLICATION: This study demonstrates that cysteamine-modified gold nanoparticles could be used as a rapid and efficient tool for gentamicin detection. This technique is cheaper, simpler, and more effective than many other methods that are currently used for detecting the antibiotic in industrial and commercial applications. It has a great potential to be practically applied as a rapid screening method for gentamicin and gentamicin-like compounds in food and environmental samples. PMID- 29786854 TI - Muffins Elaborated with Optimized Monoglycerides Oleogels: From Solid Fat Replacer Obtention to Product Quality Evaluation. AB - : This study demonstrates the effectiveness of using oleogels from high oleic sunflower oil (HOSO) and monoglycerides as solid fat replacers in a sweet bakery product. Firstly, a methodology to obtain oleogels with desired properties based on mathematical models able to describe relationships between process and product characteristics variables followed by multi-objective optimization was applied. Later, muffins were prepared with the optimized oleogels and their physicochemical and textural properties were compared with those of muffins formulated using a commercial margarine (Control) or only HOSO. Furthermore, the amount of oil released from muffins over time (1, 7, and 10 days) was measured to evaluate their stability. The replacement of commercial margarine with the optimized oleogels in muffin formulation led to the obtention of products with greater spreadability, higher specific volume, similar hardness values, and a more connected and homogeneous crumb structure. Moreover, these products showed a reduction of oil migration of around 50% in contrast to the Control muffins after 10 days of storage, which indicated that the optimized oleogels can be used satisfactorily to decrease oil loss in this sweet baked product. Fat replacement with the optimized monoglycerides oleogels not only had a positive impact on the quality of the muffins, but also allowed to improve their nutritional profile (without trans fat and low in saturated fat). PRACTICAL APPLICATION: The food industry demands new ways to reduce the use of saturated and trans fats in food formulations. To contribute to this search, oleogels from high oleic sunflower oil and saturated monoglycerides were prepared under optimized conditions in order to obtain a product with similar functionality to margarine, and its potential application as a semisolid fat ingredient in muffins was evaluated. Muffins formulated with oleogels showed an improved quality compare with those obtained using a commercial margarine with the added benefit of a healthier nutritional profile. PMID- 29786855 TI - Speciation of Bio-Available Iodine in Abalone (Haliotis discus hannai) by High Performance Liquid Chromatography Hyphenated with Inductively Coupled Plasma-Mass Spectrometry Using an In Vitro Method. AB - : Abalone is one of the most valuable marine products found in East Asia because it is rich in nutritious substances including iodine. In this study, the in vitro dialyzability approach was used to assess the bio-available iodine species in abalone. Iodide, iodate, 3-iodo-L-tyrosine (MIT), and 3,5-diiodo-L-tyrosine (DIT) were separated by high-performance liquid chromatography hyphenated with inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). To assure the consistency, reliability, and accuracy of the data, the method was validated. Comparison of the total iodine in abalone muscle and viscera indicated that abalone muscle showed greater digestion/absorption efficiency than abalone viscera (digestion efficiency: 68.13 +/- 2.59% and 47.88 +/- 5.76% and absorption efficiency: 59.78 +/- 2.93% and 35.12 +/- 1.43% for abalone viscera and muscle, respectively). However, evaluation of the sum of the analyzed iodine species targeted in this study by HPLC-ICP-MS indicated that abalone muscle showed lower digestion efficiency and similar absorption efficiency compared to that of abalone viscera (digestion efficiency: 35.52 +/- 5.41% and 28.84 +/- 1.83%; absorption efficiency: 23.56 +/- 4.38% and 27.56 +/- 1.51% for abalone viscera and muscle, respectively). The main forms of iodine detected in abalone muscle were iodide and MIT, whereas iodide was the major form in abalone viscera. PRACTICAL APPLICATION: The bio-available iodine in abalone was quantified via an in vitro method employing HPLC-ICP-MS. The results of this study indicated that abalone is feasible as a new iodine source and may prospectively find application in iodine-fortified foods. PMID- 29786856 TI - Characterization of Pectins Extracted from Different Varieties of Pink/Red and White Grapefruits [Citrus Paradisi (Macf.)] by Thermal Treatment and Thermosonication. AB - : The physical and chemical properties of pectin extracts obtained from different white and pink/red varieties of grapefruit [Citrus paradisi (Macf.)], using both conventional heating (CHE) and thermosonication (TS), were investigated. The content of galacturonic acid (GalA), degree of esterification (%DM), color and antioxidant capacity were analyzed. Fourier-Transform Infrared Spectroscopy (FTIR) associated with multivariate analysis enabled a structural comparison among the pectin extracts, and differential scanning calorimetry (DSC) completed a full landscape of the investigated extracts. Pectin extracts obtained by CHE showed mostly higher GalA than those obtained by TS. All the extracts had a high antioxidant capacity, as determined by 2,2 diphenyl 1-picrylhydrazyl (DPPH* ) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS* +) assays, and a high correlation with the GalA content. The main differences observed in the FTIR spectra occurred in the 1200 to 900 cm-1 region (differences in GalA). The glass transition temperatures (Tgs) of all extracts were above 85 degrees C, making them interesting as stabilizing agents for the food industry. PRACTICAL APPLICATION: A wide database for the characterization of pectin extracts from grapefruits was obtained. The relationship between the extraction method and the source of pectins, with the physicochemical and antioxidant properties provided great support for their application in the food industry. PMID- 29786857 TI - Effect of OATP1B1/1B3 Inhibitor GDC-0810 on the Pharmacokinetics of Pravastatin and Coproporphyrin I/III in Healthy Female Subjects. AB - Developed as an oral anticancer drug to treat estrogen receptor-positive breast cancer, GDC-0810 was shown to be a potent inhibitor of organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/1B3) from an in vitro assay. A clinical study was conducted to assess the drug-drug interaction potential between GDC-0810 and pravastatin, which is a relatively selective and sensitive OATP1B1/1B3 substrate. Fifteen healthy female subjects of non-childbearing potential were enrolled in the study. On day 1 in period 1, a single 10-mg dose of pravastatin was administered to all subjects. Following a 4-day washout period, 600 mg of GDC 0810 was administered once daily on days 5 through 8 in period 2 to achieve steady-state concentrations. On day 7, a single dose of 10-mg pravastatin was coadministered with the 600-mg GDC-0810 dose. Concentrations of pravastatin (periods 1 and 2) and GDC-0810 (period 2 only) were quantified in blood samples and subsequently used to calculate the pharmacokinetics (PK) parameters. The pravastatin mean maximal concentration and area under the curve values were approximately 20% and 41% higher, respectively, following pravastatin coadministration with GDC-0810 compared to pravastatin alone. Based on the magnitude of change in this drug-drug interaction study, dose adjustments for pravastatin (and other OATP1B1/1B3 substrates) were not considered necessary when administered with GDC-0810. Retrospectively, the endogenous biomarkers of OATP1B1/1B3, coproporphyrin I and III, were also measured and showed changes comparable to those of pravastatin, indicating their utility in detecting weak inhibition of OATP1B1/1B3 in the clinical setting. PMID- 29786858 TI - Ecosystem heterogeneity and diversity mitigate Amazon forest resilience to frequent extreme droughts. AB - The impact of increases in drought frequency on the Amazon forest's composition, structure and functioning remain uncertain. We used a process- and individual based ecosystem model (ED2) to quantify the forest's vulnerability to increased drought recurrence. We generated meteorologically realistic, drier-than-observed rainfall scenarios for two Amazon forest sites, Paracou (wetter) and Tapajos (drier), to evaluate the impacts of more frequent droughts on forest biomass, structure and composition. The wet site was insensitive to the tested scenarios, whereas at the dry site biomass declined when average rainfall reduction exceeded 15%, due to high mortality of large-sized evergreen trees. Biomass losses persisted when year-long drought recurrence was shorter than 2-7 yr, depending upon soil texture and leaf phenology. From the site-level scenario results, we developed regionally applicable metrics to quantify the Amazon forest's climatological proximity to rainfall regimes likely to cause biomass loss > 20% in 50 yr according to ED2 predictions. Nearly 25% (1.8 million km2 ) of the Amazon forests could experience frequent droughts and biomass loss if mean annual rainfall or interannual variability changed by 2sigma. At least 10% of the high emission climate projections (CMIP5/RCP8.5 models) predict critically dry regimes over 25% of the Amazon forest area by 2100. PMID- 29786859 TI - Synergistic effects of abiotic stresses in plants: a case study of nitrogen limitation and saturating light intensity in Arabidopsis thaliana. AB - Under natural conditions, plants are regularly exposed to combinations of stress factors. A common example is the conjunction between nitrogen (N) deficiency and excess light. The combined effect of stress factors is often ignored in studies using controlled conditions, possibly resulting in misleading conclusions. To address this issue, the present study examined the physiological behavior of Arabidopsis thaliana under the effect of varying nitrogen levels and light intensities. The joint influence of low N and excess light had an adverse effect on plant growth, chlorophyll and anthocyanin concentrations, photochemical capacity and the abundance of proteins involved in carbon assimilation and antioxidative metabolism. In contrast, no adverse physiological responses were observed for plants under either nitrogen limitation or high light (HL) intensity conditions (i.e. single stress). The underlying mechanisms for the increased growth in conditions of HL and sufficient nitrogen were a combination of chlorophyll accumulation and an increased number of proteins involved in C3 carbon assimilation, amino acids biosynthesis and chloroplast development. In contrast, combined stress conditions shifts plants from growth to survival by displaying anthocyanin accumulation and an increased number of proteins involved in catabolism of lipids and amino acids as energy substrates. Ultimately switching plants development from growth to survival. Our results suggest that an assessment of the physiological response to the combined effect of multiple stresses cannot be directly extrapolated from the physiological response to a single stress. Specifically, the synergistic interaction between N deficiency and saturating light in Arabidopsis plants could not have been modeled via only one of the stress factors. PMID- 29786860 TI - Effect of cold plasma on maintaining the quality of chub mackerel (Scomber japonicus): biochemical and sensory attributes. AB - BACKGROUND: Atmospheric cold plasma (ACP) has emerged as a potential alternative to traditional methods for non-thermal food decontamination. However, few data are available about ACP treatment for seafood. In this study, dielectric barrier discharge (DBD) was applied to generate CP, and the aim of the study was to investigate the effectiveness of DBD-ACP on improving the quality of chub mackerel on the basis of chemical, microbial and sensory characteristics. RESULTS: The effect of DBD-ACP on the quality of chub mackerel (Scomber japonicus) during storage was examined. Results revealed that the optimal voltage level and exposure time of this treatment were 60 kV and 60 s respectively, and such conditions exhibited excellent inactivation efficacy and weak influence on proximate chemical compositions. Variations in total viable count (TVC), sensory scores and total volatile basic nitrogen (TVB-N) indicated that ACP treatment extended the shelf life of chub mackerel to 14 days, whereas samples without this treatment exceeded the limits of the three parameters after 6 days. The slow development rates of peroxide value (PV) and thiobarbituric acid (TBA) value implied that lipid oxidation was also effectively retarded by ACP exposure. Scanning electron microscopy confirmed that CP could effectively delay the degradation of myofibrillar proteins and enhance the stability of tissue structures. CONCLUSION: The excellent antimicrobial efficacy of ACP treatment makes it a potential and promising alternative to other seafood preservation technology. This is the first report on the application of ACP to seafood, which is essential to perishable food storage. (c) 2018 Society of Chemical Industry. PMID- 29786862 TI - Experimental fluence-modulated proton computed tomography by pencil beam scanning. AB - PURPOSE: This experimental study is aimed at demonstrating, using a simple cylindrical water phantom, the feasibility of fluence-modulated proton computed tomography (FMpCT) by pencil beam scanning (PBS) proton computed tomography (pCT). METHODS: The phase II pCT prototype of the Loma Linda U. and U. C. Santa Cruz was operated using the PBS beam line of the Northwestern Medicine Chicago Proton Center. A 20 * 10 grid of 1.37 cm full width half maximum pencil beams (PB) equally spaced by 1 cm was used to acquire 45 projections in step and shoot mode. The PB pattern's fluence was modified to allow FMpCT scans with fluence modulation factors (FMF) of 50% and 20%. A central FMpCT region of interest (FMpCT-ROI) was used to define a high image quality region. Reconstructed images were evaluated in terms of relative stopping power (RSP) accuracy and noise using annular ROIs. The FMpCT dose savings were estimated by Monte Carlo (MC) simulation of the pCT acquisitions using beam phase space distributions. PBS pCT results with homogeneous fluence were additionally compared to broad beam results in terms of RSP accuracy and noise. RESULTS: PBS pCT scans with acceptable pileup were possible, and images were comparable to previously acquired broad beam pCT images in terms of both noise and accuracy. In the FMpCT-ROI, the noise and accuracy from full fluence (FF) scans were preserved. Dose savings of up to 60% were achieved at the object's edge when using FMF of 20%. CONCLUSION: In this study, we have demonstrated that PBS pCT scans can achieve equivalent accuracy as those obtained from broad beams. The feasibility of FMpCT scans was demonstrated; image accuracy and noise were successfully preserved in the central FMpCT-ROI chosen for this study, and dose reduction of up to 60% at the object's edge was realized. PMID- 29786863 TI - Acute ammonia toxicity to the larvae (glochidia) of the tropical Australian freshwater mussel Velesunio spp. Using a modified toxicity test protocol. AB - Ammonia is recognized as a major pollutant worldwide, originating from natural and anthropogenic sources. Studies have reported that freshwater mussels are among the most sensitive taxa to ammonia, but few data are available on ammonia toxicity for the early life stages of freshwater mussels from tropical regions. We report on the modification of a 24-h acute toxicity test protocol for tropical freshwater mussels and application of the test using ammonia. Velesunio spp. from 3 different sites were used to assess the toxicity of ammonia at a targeted pH of 6.0 and a water temperature of 27.5 degrees C, which were the average annual values for some slightly to moderately acidic, soft water (3-6 mg/L as CaCO3 ) creeks of tropical northern Australia. The valve closure responses of mussel glochidia (larvae) to a sodium chloride solution were used to measure the survival endpoint. Acute toxicity estimates indicate that tropical Velesunio spp. were highly sensitive to ammonia, with 24-h exposures to ammonium sulfate generating median lethal concentration estimates ranging from 6.8 to 14.2 mg/L total ammonia nitrogen, which, when adjusted to pH 7 and 20 degrees C, were among the highest sensitivities yet reported for any freshwater mussel species, and among the highest in sensitivity for any tropical taxon. These toxicity estimates can contribute to the derivation or refinement of ammonia guideline values for freshwater ecosystems globally. Environ Toxicol Chem 2018;37:2175 2187. (c) 2018 SETAC. PMID- 29786864 TI - Testing the roles of vertical transmission and drought stress in the prevalence of heritable fungal endophytes in annual grass populations. AB - Beneficial inherited symbionts are expected to reach high prevalence in host populations, yet many are observed at intermediate prevalence. Theory predicts that a balance of fitness benefits and efficiency of vertical transmission may interact to stabilize intermediate prevalence. We established populations of grass hosts (Lolium multiflorum) that varied in prevalence of a heritable fungal endophyte (Epichloe occultans), allowing us to infer long-term equilibria by tracking change in prevalence over one generation. We manipulated an environmental stressor (elevated precipitation), which we hypothesized would reduce the fitness benefits of symbiosis, and altered the efficiency of vertical transmission by replacing endophyte-positive seeds with endophyte-free seeds. Endophytes and elevated precipitation both increased host fitness, but symbiont effects were not stronger in the drier treatment, suggesting that benefits of symbiosis were unrelated to drought tolerance. Reduced transmission suppressed the inferred equilibrium prevalence from 42.6% to 11.7%. However, elevated precipitation did not modify prevalence, consistent with the result that it did not modify fitness benefits. Our results demonstrate that failed transmission can influence the prevalence of heritable microbes and that intermediate prevalence can be a stable equilibrium due to forces that allow symbionts to increase (fitness benefits) but prevent them from reaching fixation (failed transmission). PMID- 29786865 TI - Infection with phytopathogenic bacterium inhibits melatonin biosynthesis, decreases longevity of its vector, and suppresses the free radical-defense. AB - Vector-borne phytopathogenic bacteria may alter the reproductive fitness, survival, behavior, and metabolism of their vectors. Candidatus Liberibacter asiaticus (CLas) is associated with the Huanglongbing (also known as citrus greening disease), one of the most destructive citrus diseases worldwide, and transmitted by Asian citrus psyllid, Diaphorina citri (Insecta, Hemiptera, Liviidae). The genome sequencing of CLas revealed that it does not have the ability to synthesize tryptophan, the precursor of melatonin, and it must acquire it from its host plant or insect vector to achieve its biologic processes, such as growth and multiplication. Herein, we aimed to develop a GC-MS-SIM-based method to detect the endogenous melatonin from small insects such as D. citri, and to explore the hidden relationship between melatonin content and D. citri adult survival. Then, we studied the ability of exogenous melatonin supplementation to reverse the negative effects of CLas-infection. Our findings showed that CLas-infection reduced the levels of melatonin and its biosynthetic genes (DcTPHs, DcAAAD, DcSNAT, and DcASMT) of D. citri compared to uninfected insects. In addition, CLas decreased the longevity of its vector, D. citri via the suppression of the free radical-defense associated genes (SODs, GSTs, PODs, and PHGPXs). On the other hand, melatonin supplementation could reverse the negative effects of CLas-infection. Melatonin supplementation enhanced the endogenous melatonin content, melatonin biosynthetic genes, free radical-defense associated genes, and the longevity of both healthy and CLas-infected D. citri. Furthermore, melatonin supplementation decreased the CLas bacterial population within the D. citri psyllids. Based on these findings, we hypothesize that melatonin plays multi-layered defensive roles in D. citri. These roles include acting as a natural antioxidant or as an antibacterial compound. PMID- 29786861 TI - Temporally feathered intensity-modulated radiation therapy: A planning technique to reduce normal tissue toxicity. AB - PURPOSE: Intensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy "temporally feathered radiation therapy" (TFRT). METHODS: Temporally feathered radiotherapy plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time. RESULTS: Model based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage. CONCLUSIONS: TFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the nonlinear aspects of normal tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for radiation-induced toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP). PMID- 29786866 TI - Characterization of efficacy and safety of pathogen inactivated and quarantine plasma in routine use for treatment of acquired immune thrombotic thrombocytopenic purpura. AB - BACKGROUND: Auto-immune thrombotic thrombocytopenic purpura (TTP) is a morbid multi-organ disorder. Cardiac involvement not recognized in initial disease descriptions is a major cause of morbidity. Therapeutic plasma exchange (TPE) requires exposure to multiple plasma donors with risk of transfusion-transmitted infection (TTI). Pathogen inactivation (PI) with amotosalen-UVA, the INTERCEPT Blood System for Plasma (IBSP) is licensed to reduce TTI risk. METHODS: An open label, retrospective study evaluated the efficacy of quarantine plasma (QP) and IBSP in TTP and defined treatment emergent cardiac abnormalities. Medical record review of sequential patient cohorts treated with QP and IBSP characterized efficacy by remission at 30 and 60 days (d) of treatment, time to remission, and volume (L/kg) of plasma required. Safety outcomes focused on cardiac adverse events (AE), relapse rates, and mortality. RESULTS: Thirty-one patients (18 IBSP and 13 QP) met study criteria for auto-immune TTP. The proportions (%) of patients in remission at 30 d (IBSP = 61.1, QP = 46.2, P = 0.570) and 60 d (IBSP = 77.8, QP = 76.9, P = 1.00) were not different. Median days to remission were less for IBSP (15.0 vs. 24.0, P = 0.003). Relapse rates (%) 60 d after remission were not different between cohorts (IBSP = 7.1, QP = 40.0, P = 0.150). ECG abnormalities before and during TPE were frequent; however, cardiac AE and mortality were not different between treatment cohorts. CONCLUSIONS: Cardiac and a spectrum of ECG findings are common in TTP. In this study, IBSP and QP had similar therapeutic profiles for TPE. PMID- 29786867 TI - Growth hormone-releasing hormone antagonists reduce prostatic enlargement and inflammation in carrageenan-induced chronic prostatitis. AB - BACKGROUND: Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial-to-mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions. Our current study was aimed at the investigation of the beneficial effects of GHRH antagonists in lambda carrageenan-induced chronic prostatitis and at probing the downstream molecular pathways that are implicated in GHRH signaling. METHODS: To demonstrate the complications triggered by recurrent/chronic prostatic inflammation in Sprague Dawley rats, 50 MUL 3% carrageenan was injected into both ventral prostate lobes two times, 3 weeks apart. GHRH antagonist, MIA-690, was administered 5 days after the second intraprostatic injection at 20 MUg daily dose for 4 weeks. GHRH induced signaling events were identified in BPH-1 and in primary prostate epithelial (PrEp) cells at 5, 15, 30, and 60 min with Western blot. RESULTS: Inflammation induced prostatic enlargement and increased the area of the stromal compartment whereas treatment with the GHRH antagonist significantly reduced these effects. This beneficial activity was consistent with a decrease in prostatic GHRH, inflammatory marker COX-2, growth factor IGF-1 and inflammatory and EMT marker TGF-beta1 protein levels and the expression of multiple genes related to EMT. In vitro, GHRH stimulated multiple pathways involved in inflammation and growth in both BPH-1 and PrEp cells including NFkappaB p65, AKT, ERK1/2, EGFR, STAT3 and increased the levels of TGF-beta1 and Snail/Slug. Most interestingly, GHRH also stimulated the transactivation of the IGF receptor. CONCLUSIONS: The study demonstrates that GHRH antagonists could be beneficial for the treatment of prostatic inflammation and BPH in part by inhibiting the growth promoting and inflammatory effects of locally produced GHRH. PMID- 29786868 TI - CIS-Acting Allele-Specific Expression Differences Induced by Alcohol and Impacted by Sex as Well as Parental Genotype of Origin. AB - BACKGROUND: Alcohol use disorders (AUDs) are influenced by complex interactions between the genetics of the individual and their environment. We have previously identified hundreds of polygenic genetic variants between the selectively bred high- and low-alcohol drinking (HAD and LAD) rat lines. Here, we report allele specific expression (ASE) differences, between the HAD2 and LAD2 rat lines. METHODS: The HAD2 and LAD2 rats, which have been sequenced, were reciprocally crossed to generate 10 litters of F1 progeny. For 5 of these litters, the sire was HAD2, and for the other 5 litters, the sire was a LAD2. From these 10 litters, 2 males and 2 females were picked from each F1 litter (N = 40 total). The F1 pups were divided, balancing for sex and direction of cross, into an alcohol (15%) versus a water control group. Alcohol drinking started in the middle of adolescence (~postnatal day 35) and lasted 9 weeks. At the end of these treatments, rats were euthanized, the nucleus accumbens was dissected, and RNA was processed for RNA-sequencing and ASE analyses. RESULTS: Analyses revealed that adolescent ethanol (EtOH) drinking, individual EtOH drinking levels, parentage, and sex-of-animal affected ASEs of about 300 genes. The identified genes included those associated with EtOH metabolism (e.g., Aldh2); neuromodulatory function (e.g., Cckbr, Slc6a7, and Slc1a1); ion channel activity (e.g., Kcnc3); and other synaptic and epigenetic functions. CONCLUSIONS: These data indicate that EtOH drinking differentially amplified paternal versus maternal allelic contribution to the transcriptome. We hypothesize that this was due, at least in part, to EtOH-induced changes in cis-regulation of polymorphisms previously identified between the HAD2 and LAD2 rat lines. This report highlights the complexity of gene-by-environment interactions mediating a genetic predisposition for, and/or the active development of, AUDs. PMID- 29786869 TI - Rare labial ulcer related to the use of all-trans retinoic acid in a patient with acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is the first-choice therapy for the treatment of this disease, but has been associated with side effects, the most serious of which is retinoic acid syndrome (RAS). RAS is characterized by unexplained fever, dyspnea, pulmonary infiltrate, leukocytosis and nephropathy. Genital ulcers have been described in some cases, but only two cases of oral ulcers related to this syndrome have been described in the literature. This paper describes the third case of oral ulceration related to ATRA in a 32-year-old white man with diagnosis of APL. Clinicians should know the side effects of ATRA and identify oral ulcers resulting from this therapy. The prompt identification of these ulcers enables the institution of appropriate treatment and can therefore contribute to continuation of the patient's cancer treatment. PMID- 29786870 TI - The association between local atherosclerosis of the prostatic artery and benign prostatic enlargement in humans: Putative mechanism of chronic ischemia for prostatic enlargement. AB - BACKGROUND: To investigate the possible pathogenesis of the benign prostatic enlargement (BPE) induced by local atherosclerosis, the association between local atherosclerosis and prostatic enlargement was investigated, and molecular biological analyses were performed using human prostatectomy specimens. METHODS: A total of 69 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) participated in this prospective study. To evaluate actual local atherosclerosis, prostatic arteries were removed during RARP. Microscopic assessment of local atherosclerosis was classified as one of three degrees of narrowing (minimal, moderate, and severe) according to the degree of obstruction of the inner cavity of the prostatic artery. The expressions of several mediators related to chronic ischemia and cell proliferation of the prostate were investigated by immunohistochemistry. RESULTS: The median age of the present cohort was 68 (range: 55-75) years. Although there was no relationship between local atherosclerosis and lower urinary symptoms evaluated by questionnaires, local atherosclerosis was significantly more severe in patients who had a history of treatment for benign prostatic hyperplasia (P = 0.02). Prostate size was significantly larger in the severe local atherosclerosis group than in the minimal and moderate local atherosclerosis groups (P < 0.001 and P = 0.03, respectively). Thepositive expression rates of hypoxia-inducible factor (HIF) 1alpha, malondialdehyde (MDA), transforming growth factor (TGF)-beta1 , and basic fibroblast growth factor (bFGF) in the prostate were significantly higher in patients with local atherosclerosis than in patients without local atherosclerosis (all P < 0.01, respectively). CONCLUSIONS: In human surgical specimens, there is evidence that local atherosclerosis of the prostatic artery is significantly associated with prostate size. Given the molecular evidence provided in this study, the putative mechanism for this relationship is that chronic ischemia induced upregulation of oxidative stress pathways, leading to BPE. PMID- 29786872 TI - Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder. AB - Bornavirus infection is observed in both animals, including humans. However, bornavirus epidemiology in humans, especially in children, remains unclear. Here, we evaluated antibodies against bornaviruses in Japanese children with autism spectrum disorder (ASD) using immunofluorescence analysis, western blotting, and radio ligand assay. The prevalence of antibodies against bornavirus-specific speckles, N, and P proteins were 22%, 48%, and 33%, respectively, in the ASD children. According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in the ASD children. This is the first report of the serological prevalence of bornavirus in Japanese children. Our results provide valuable baseline-data regarding bornavirus epidemiology in children for future studies. PMID- 29786873 TI - In vivo profiling of four centrally administered opioids for antinociception, constipation and respiratory depression: Between-colony differences in Sprague Dawley rats. AB - Outbred rodent stocks including Sprague Dawley rats, are known for their genetic diversity and so they are often used to develop animal models of human disease. Although between-colony differences in pharmaco-behavioural studies have been published previously, a direct head-to-head comparison study, whereby all research was performed in the same laboratory by the same experimenter utilising the supraspinal route of drug administration in the same strain of rat, is lacking. Herein, we report our head-to-head comparison study, involving assessment of antinociception, constipation and respiratory depression evoked by single bolus intracerebroventricular (ICV) doses of morphine, buprenorphine, DPDPE and U69,593 using male Sprague Dawley rats sourced from a different breeding colony (BC2) from that (BC1) used by us previously. Our data show that there are marked differences in the potency rank order for morphine and buprenorphine between rats sourced from BC2 and BC1. Although ICV morphine evoked a bell-shaped dose-response curve in the constipation test for rats from both colonies, this occurred at higher doses for rats from BC2. In conclusion, our head-to-head comparison shows considerable between-colony differences for the same rat strain, in the potency rank order of two clinically important strong opioid analgesics given by the ICV route. PMID- 29786871 TI - Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs. AB - BACKGROUND: Transcriptional differences between heterogeneous stock mice and high drinking-in-the-dark selected mouse lines have previously been described based on microarray technology coupled with network-based analysis. The network changes were reproducible in 2 independent selections and largely confined to 2 distinct network modules; in contrast, differential expression appeared more specific to each selected line. This study extends these results by utilizing RNA-Seq technology, allowing evaluation of the relationship between genetic risk and transcription of noncoding RNA (ncRNA); we additionally evaluate sex-specific transcriptional effects of selection. METHODS: Naive mice (N = 24/group and sex) were utilized for gene expression analysis in the ventral striatum; the transcriptome was sequenced with the Illumina HiSeq platform. Differential gene expression and the weighted gene co-expression network analysis were implemented largely as described elsewhere, resulting in the identification of genes that change expression level or (co)variance structure. RESULTS: Across both sexes, we detect selection effects on the extracellular matrix and synaptic signaling, although the identity of individual genes varies. A majority of nc RNAs cluster in a single module of relatively low density in both the male and female network. The most strongly differentially expressed transcript in both sexes was Gm22513, a small nuclear RNA with unknown function. Associated with selection, we also found a number of network hubs that change edge strength and connectivity. At the individual gene level, there are many sex-specific effects; however, at the annotation level, results are more concordant. CONCLUSIONS: In addition to demonstrating sex-specific effects of selection on the transcriptome, the data point to the involvement of extracellular matrix genes as being associated with the binge drinking phenotype. PMID- 29786875 TI - Serum lipid levels are associated with allergic rhinitis, nasal symptoms, peripheral olfactory function, and nasal airway patency in children. PMID- 29786874 TI - Meta-Analysis of the Association of Alcohol-Related Social Media Use with Alcohol Consumption and Alcohol-Related Problems in Adolescents and Young Adults. AB - Despite the pervasive use of social media by young adults, there is comparatively little known about whether, and how, engagement in social media influences this group's drinking patterns and risk of alcohol-related problems. We examined the relations between young adults' alcohol-related social media engagement (defined as the posting, liking, commenting, and viewing of alcohol-related social media content) and their drinking behavior and problems. We conducted a systematic review and meta-analysis of studies evaluating the association of alcohol consumption and alcohol-related problems with alcohol-related social media engagement. Summary baseline variables regarding the social media platform used (e.g., Facebook and Twitter), social media measures assessed (e.g., number of alcohol photographs posted), alcohol measures (e.g., Alcohol Use Disorders Identification Test and Timeline Follow back Interview), and the number of time points at which data were collected were extracted from each published study. We used the Q statistic to examine heterogeneity in the correlations between alcohol related social media engagement and both drinking behavior and alcohol-related problems. Because there was significant heterogeneity, we used a random-effects model to evaluate the difference from zero of the weighted aggregate correlations. We used metaregression with study characteristics as moderators to test for moderators of the observed heterogeneity. Following screening, 19 articles met inclusion criteria for the meta-analysis. The primary findings indicated a statistically significant relationship and moderate effect sizes between alcohol-related social media engagement and both alcohol consumption (r = 0.36, 95% CI: 0.29 to 0.44, p < 0.001) and alcohol-related problems (r = 0.37, 95% CI: 0.21 to 0.51, p < 0.001). There was significant heterogeneity among studies. Two significant predictors of heterogeneity were (i) whether there was joint measurement of alcohol-related social media engagement and drinking behavior or these were measured on different occasions and (ii) whether measurements were taken by self-report or observation of social media engagement. We found moderate-sized effects across the 19 studies: Greater alcohol-related social media engagement was correlated with both greater self-reported drinking and alcohol-related problems. Further research to determine the causal direction of these associations could provide opportunities for social media-based interventions with young drinkers aimed at reducing alcohol consumption and alcohol-related adverse consequences. PMID- 29786876 TI - Temporal and long-term gut microbiota variation in allergic disease: A prospective study from infancy to school age. AB - BACKGROUND: Compositional changes in the early-life gut microbiota have been implicated in IgE-associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation. METHODS: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL-10 and FOXP3 mRNA copies were determined using real-time quantitative reverse transcriptase-PCR. RESULTS: At 8 years of age, 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08). CONCLUSIONS: We identified both temporal and long-term variation in the differential abundance of specific bacterial genera in children developing IgE associated allergic disease. Improved dietary interventions aiming at expanding immune-modulatory taxa could be studied for prevention of allergic disease. PMID- 29786877 TI - Morphomic Malnutrition Score: A Standardized Screening Tool for Severe Malnutrition in Adults. AB - BACKGROUND: Granular diagnostic criteria for adult malnutrition are lacking. OBJECTIVE: This study uses analytic morphomics to define the Morphomic Malnutrition Score (MMS), a robust screening tool for severe malnutrition. METHODS: The study population (n = 643) consisted of 2 cohorts: 1) 124 emergency department patients diagnosed with severe malnutrition by a registered dietitian (RD) and an available computed tomography (CT) scan within 2 days of RD evaluation, and 2) 519 adult kidney donor candidates to represent a healthy cohort. Body composition markers of muscle area and abdominal adiposity were measured from patient CT scans using analytic morphomic assessment, and then converted to sex- and age-adjusted percentiles using the Reference Analytic Morphomics Population (RAMP). RAMP consists of 6000 patients chosen to be representative of the general population. The combined cohort was then randomly divided into training (n = 453) and validation (n = 190) sets. MMS was derived using logistic regression. The model coefficients were transformed into a score, normalized from 0 to 10 (10 = most severe). RESULTS: Severely malnourished patients had lower amounts of muscle and fat than kidney donors, specifically for dorsal muscle group area at the twelfth thoracic vertebral level (P < 0.001), psoas muscle area at the fourth lumbar vertebral level (P < 0.001), and subcutaneous fat area at the third lumbar vertebral level (P < 0.001)-all parameters in MMS. MMS for severely malnourished patients was higher than kidney donors (7.7 +/- 2.2 vs 3.8 +/- 2.0, respectively; P-value < 0.001). An MMS > 6.1 was accurate in determining nutrition diagnosis (82.1% sensitivity; 88.3% specificity; 85.2% balanced accuracy). CONCLUSIONS: MMS provides an evidence based, granular assessment to distinguish severely malnourished adults from a healthy population. PMID- 29786879 TI - Comorbidity of viral hepatitis and chronic spontaneous urticaria: A systematic review. AB - Chronic viral infections including those by hepatitis B (CHB) virus and hepatitis C (CHC) virus have been reported to be comorbidities of chronic spontaneous urticaria (CSU). Here, we performed the first comprehensive review of the peer reviewed literature (PubMed, Web of Science and Google Scholar) on the prevalence of CHB and CHC in patients with CSU and vice versa. The prevalence of CHB and CHC in CSU does not appear to be increased. Less than 5% and 2% of patients with CSU have markers of CHB and CHC, respectively, according to most of the 32 studies reviewed. Urticarial rash including CSU occurs in <=3% of patients with CHC as reported by most of 20 studies analysed. Very few patients have been assessed for the effects of antiviral hepatitis treatment on their CSU, and two but not all reportedly showed improvement. Hepatitis B/C infections appear unlikely to be linked to CSU. We suggest that routine screening for these infections in patients with CSU is not relevant or cost-effective and should not be performed unless liver function tests are abnormal, risk factors or symptoms of viral hepatitis are present, or urticarial vasculitis is suspected. PMID- 29786878 TI - Dietary Omega-3 Fatty Acids Differentially Impact Acute Ethanol-Responsive Behaviors and Ethanol Consumption in DBA/2J Versus C57BL/6J Mice. AB - BACKGROUND: Complex interactions between environmental and genetic factors influence the risk of developing alcohol use disorder (AUD) in humans. To date, studies of the impact of environment on AUD risk have primarily focused on psychological characteristics or on the effects of developmental exposure to ethanol (EtOH). We recently observed that modifying levels of the long-chain omega-3 (LC omega-3) fatty acid, eicosapentaenoic acid (EPA), alters acute physiological responses to EtOH in Caenorhabditis elegans. Because mammals derive omega-3 fatty acids from their diet, here we asked if manipulating dietary levels of LC omega-3 fatty acids can affect EtOH-responsive behaviors in mice. METHODS: We used 2 well-characterized inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), which differ in their responses to EtOH. Age-matched young adult male mice were maintained on isocaloric diets that differed only by being enriched or depleted in LC omega-3 fatty acids. Animals were subsequently tested for acute EtOH sensitivity (locomotor activation and sedation), voluntary consumption, and metabolism. Fat deposition was also determined. RESULTS: We found that dietary levels of LC omega-3s altered EtOH sensitivity and consumption in a genotype specific manner. Both B6 and D2 animals fed high LC omega-3 diets demonstrated lower EtOH-induced locomotor stimulation than those fed low LC omega-3 diets. EtOH sedation and EtOH metabolism were greater in D2, but not B6 mice on the high LC omega-3 diet. Conversely, LC omega-3 dietary manipulation altered EtOH consumption in B6, but not in D2 mice. B6 mice on a high LC omega-3 diet consumed more EtOH in a 2-bottle choice intermittent access model than B6 mice on a low LC omega-3 diet. CONCLUSIONS: Because EtOH sensitivity is predictive of risk of developing AUD in humans, our data indicate that dietary LC omega-3 levels should be evaluated for their impact on AUD risk in humans. Further, these studies indicate that genetic background can interact with fatty acids in the diet to significantly alter EtOH-responsive behaviors. PMID- 29786880 TI - Metagenomic study of bacterial microbiota in persistent endodontic infections using Next-generation sequencing. AB - AIM: To determine the bacterial microbiota in root canals associated with persistent apical periodontitis and their relationship with the clinical characteristics of patients using next-generation sequencing (NGS). METHODOLOGY: Bacterial samples from root canals associated with teeth having persistent apical periodontitis were taken from 24 patients undergoing root canal retreatment. Bacterial DNA was extracted, and V3-V4 variable regions of the 16S rRNA gene were amplified. The amplification was deep sequenced by Illumina technology to establish the metagenetic relationships among the bacterial species identified. The composition and diversity of microbial communities in the root canal and their relationships with clinical features were analysed. Parametric and nonparametric tests were used to analyse differences between patient characteristics and microbial data. RESULTS: A total of 86 different operational taxonomic units (OTUs) were identified and Good's nonparametric coverage estimator method indicated that 99.9 +/- 0.00001% diversity was recovered per sample. The largest number of bacteria belonged to the phylum Proteobacteria. According to the medical history from the American Society of Anesthesiologists (ASA) Classification System, ASA II-III had higher richness estimates and distinct phylogenetic relationships compared to ASA I individuals (P < 0.05). Periapical index (PAI) score 5 was associated with increased microbiota diversity in comparison to PAI score 4, and this index was reduced in symptomatic patients. CONCLUSIONS: Based on the findings of this study, it is possible to suggest a close relationship between several clinical features and greater microbiota diversity with persistent endodontic infections. This work provides a better understanding on how microbial communities interact with their host and vice versa. PMID- 29786881 TI - Small RNAs and Transposable Elements Are Key Components in the Control of Adaptive Evolution in Eukaryotes. PMID- 29786882 TI - Feasibility of Assessing Prognostic Nutrition Index in Patients With Rectal Cancer Who Receive Preoperative Chemoradiotherapy. AB - BACKGROUND: Malnutrition can adversely affect treatment responses and oncological outcomes in cancer patients. However, among patients with rectal cancer who undergo chemoradiotherapy (CRT), the significance of peri-treatment nutrition assessment as a predictor of treatment response and outcome remains unclear. OBJECTIVE: The aim of this study was to determine whether the Prognostic Nutrition Index (PNI) based on peri-treatment serum can be used as a predictor of treatment response and outcome in patients with rectal cancer who undergo CRT. DESIGN, SETTING, AND PATIENTS: We analyzed 114 patients with rectal cancer who received preoperative CRT followed by total mesorectal excision at our institution. RESULTS: Post-CRT PNI was significantly lower than pre-CRT PNI in rectal cancer patients. Although post-CRT PNI did not significantly correlate with either overall survival or disease-free survival, low pre-CRT PNI was significantly associated with shorter overall survival and disease-free survival in this population and was also an independent risk factor for ineffectiveness of long-course preoperative CRT. Finally, low pre-CRT PNIs were a stronger indicator of poor prognosis and early recurrence in patients with pathological lymph node metastasis (who generally need to receive postoperative chemotherapy), than in those with no pathological lymph node metastasis. CONCLUSION: Pretreatment PNI could be useful in evaluating and managing patients with rectal cancer who undergo CRT followed by curative resection. PMID- 29786883 TI - Left ventricular aneurysms in hypertrophic cardiomyopathy with midventricular obstruction: A systematic review of literature. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) with or without left ventricular apical aneurysm (LVA) had been studied in the past. Midventricular obstruction associated with HCM and LVA is a unique entity that has not been distinguished previously as a separate phenotypic disease in HCM patients. METHODS: A systematic review of Pubmed and Google Scholar was conducted from inception until September 2017 for all observational studies conducted on HCM with midventricular obstruction and LVA. RESULTS: A total of 94 patients from 39 studies were included in our analysis. The mean age of the patients was 58.05 +/- 11.76 years with 59.6% being males. The most common electrocardiographic finding was T wave inversion occurring in 13.8% of the cases followed by ST elevation (9.5%). Maximal left ventricle (LV) wall thickness was reported 18.89 +/- 5.19 mm on transthoracic echocardiography and paradoxical jet flow was detected in 29.8% of patients. Beta-blockers (58.5%) were the most common drug therapy at baseline and amiodarone (10.6%) was the most common antiarrhythmic used for ventricular tachycardia (VT). The most common complication, VT, occurred in 39.3% of cases and the incidence of all-cause mortality was 13.8 % over 16 +/- 20.1 months follow-up. Implantable cardioverter defibrillator (ICD) was used in 37.2% of patients; 25.7% of patients with ICD received appropriate shock therapy. CONCLUSION: HCM with LVA and midventricular obstruction is a unique entity that appears to be associated with high incidence of morbidity and mortality. Thus, early diagnosis and therapeutic intervention is recommended for management of this condition. PMID- 29786885 TI - Automated Buildup of Biomimetic Films in Cell Culture Microplates for High Throughput Screening of Cellular Behaviors. AB - An automatic method is established for layer-by-layer (LbL) assembly of biomimetic coatings in cell culture microplates using a commercial liquid handling robot. Highly homogeneous thin films are formed at the bottom of each microwell. The LbL film-coated microplates are compatible with common cellular assays, using microplate readers and automated microscopes. Cellular adhesion is screened on crosslinked and peptide-functionalized LbL films and stem cell differentiation in response to increasing doses of bone morphogenetic proteins (2, 4, 7, 9). This method paves the way for future applications of LbL films in cell-based assays for regenerative medicine and high-throughput drug screening. PMID- 29786886 TI - Predictors of Treatment Completion for Families Referred to Trauma-Focused Cognitive Behavioral Therapy After Child Abuse. AB - Despite advances in the dissemination of evidence-based therapy for abuse-related traumatic stress, many referred children fail to complete treatment. Using archival data from a sample of children participating in trauma-focused cognitive behavioral therapy (TF-CBT) at a hospital-based child advocacy center, analyses explored the impact of baseline child traumatic stress symptoms, a second (nonprimary) caregiver's treatment attendance, and the number of assessment sessions on treatment completion while controlling for demographic variables. We conducted analyses separately for the total sample (n = 77) and for a subsample of children 6 years of age or older (n = 65) who completed measures of traumatic stress. Families who completed TF-CBT had fewer pretreatment assessment sessions, odds ratio (OR) = 0.41, 95% CI [0.19, 0.88], and greater nonprimary caregiver session attendance, OR = 1.30, 95% CI [1.03, 1.64], than families who did not complete treatment. Child age, race, and insurance status did not predict treatment completion. Among children at least 6 years of age, treatment completion was related to younger child age, OR = 0.76, 95% CI [0.59, 0.98], and fewer diagnostic evaluation sessions, OR = 0.29, 95% CI [0.11, 0.74], but not to baseline traumatic stress symptoms. Findings may suggest benefits of shortening the assessment period and including a second caregiver in TF-CBT. PMID- 29786884 TI - Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study. AB - Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. (c) 2018 American Society for Bone and Mineral Research. PMID- 29786887 TI - Perovskite Solar Cells with Inorganic Electron- and Hole-Transport Layers Exhibiting Long-Term (~500 h) Stability at 85 degrees C under Continuous 1 Sun Illumination in Ambient Air. AB - Despite the high power conversion efficiency (PCE) of perovskite solar cells (PSCs), poor long-term stability is one of the main obstacles preventing their commercialization. Several approaches to enhance the stability of PSCs have been proposed. However, an accelerating stability test of PSCs at high temperature under the operating conditions in ambient air remains still to be demonstrated. Herein, interface-engineered stable PSCs with inorganic charge-transport layers are shown. The highly conductive Al-doped ZnO films act as efficient electron transporting layers as well as dense passivation layers. This layer prevents underneath perovskite from moisture contact, evaporation of components, and reaction with a metal electrode. Finally, inverted-type PSCs with inorganic charge-transport layers exhibit a PCE of 18.45% and retain 86.7% of the initial efficiency for 500 h under continuous 1 Sun illumination at 85 degrees C in ambient air with electrical biases (at maximum power point tracking). PMID- 29786888 TI - Injectable Bioresponsive Gel Depot for Enhanced Immune Checkpoint Blockade. AB - Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed based on a thermogelling reactive oxygen species (ROS)-responsive polypeptide gel for sustained release of anti-programmed cell death-ligand 1 antibody and dextro-1-methyl tryptophan, inhibitor of indoleamine-2,3-dioxygenase with leveraging the ROS level in the tumor microenvironment. This bioresponsive gel depot can effectively reduce the local ROS level and facilitate release of immunotherapeutics, which leads to enhanced anti-melanoma efficacy in vivo. PMID- 29786889 TI - A Novel Conductive Mesoporous Layer with a Dynamic Two-Step Deposition Strategy Boosts Efficiency of Perovskite Solar Cells to 20. AB - Lead halide perovskite solar cells (PSCs) with the high power conversion efficiency (PCE) typically use mesoporous metal oxide nanoparticles as the scaffold and electron-transport layers. However, the traditional mesoporous layer suffers from low electron conductivity and severe carrier recombination. Here, antimony-doped tin oxide nanorod arrays are proposed as novel transparent conductive mesoporous layers in PSCs. Such a mesoporous layer improves the electron transport as well as light utilization. To resolve the common problem of uneven growth of perovskite on rough surface, the dynamic two-step spin coating strategy is proposed to prepare highly smooth, dense, and crystallized perovskite films with micrometer-scale grains, largely reducing the carrier recombination ratio. The conductive mesoporous layer and high-quality perovskite film eventually render the PSC with a remarkable PCE of 20.1% with excellent reproducibility. These findings provide a new avenue to further design high efficiency PSCs from the aspect of carrier transport and recombination. PMID- 29786890 TI - Thrombotic and hemorrhagic complications during visceral transplantation: risk factors, and association with intraoperative disseminated intravascular coagulation-like thromboelastographic qualities: a single-center retrospective study. AB - This study describes the risk of thrombotic and hemorrhagic complications, both intraoperatively, and up to 1 month following visceral transplantation. Data from 48 adult visceral transplants performed between 2010 and 2017 were retrospectively studied [32 multivisceral (MVTx); 10 isolated intestine; six modified-MVTx]. Intraoperatively, intracardiac thrombosis (ICT)/pulmonary embolism (PE) occurred in 25%, 0% and 0% of MVTx, isolated intestine and modified MVTx, respectively, and was associated with 50% (4/8) mortality. Preoperative portal vein thrombosis (PVT) was a significant risk factor for ICT/PE (P = 0.0073). Thromboelastography resembling disseminated intravascular coagulation (DIC) (r time <4 mm combined with fibrinolysis or flat-line) was statistically associated with occurrence of ICT/PE (P < 0.0001). Compared to subgroup without ICT/PE, occurrence of ICT/PE was associated with an increased demand for all blood product components both overall, and each surgical stage. Hyperfibrinolysis (56%) was identified as cause of bleeding in MVTx. Incidence of postoperative thrombotic event at 1 month was 25%, 30% and 17% for MVTx, isolated intestine and modified MVTx, respectively. Incidence of postoperative bleeding complications at 1 month was 11%, 20% and 17% for MVTx, isolated intestine and modified MVTx. In conclusion, MVTx recipients with preoperative PVT are at an increased risk of developing intraoperative life-threatening ICT/PE events associated with DIC-like coagulopathy. PMID- 29786891 TI - Supporting Asylum Seekers: Clinician Experiences of Documenting Human Rights Violations Through Forensic Psychological Evaluation. AB - The United States permits foreign nationals to apply for asylum if they have experienced persecution or have a fear of future persecution. In order to meet the criteria for persecution, the harm inflicted upon the asylum seeker does not need to be or have been physical and can include psychological sequelae. In an effort to document persecution, lawyers seek the assistance of health professionals when preparing their clients' asylum applications. Mental health professionals work to corroborate psychological evidence of the asylum seeker's report of ill treatment through evaluation and presentation of their findings in the form of legal affidavits. This study gathered the experiences of 15 mental health clinicians who conduct forensic psychological evaluations and document the impact of torture and other human rights violations on asylum seekers. We analyzed the resulting interview transcripts using a consensual qualitative research (CQR) approach. The results of the study highlight challenges associated with this work, suggest recommendations for training, and encourage advocacy endeavors by mental health professionals who provide these services. PMID- 29786893 TI - Primary cystic duct carcinoma diagnosed by targeted biopsy with digital cholangioscopy. PMID- 29786892 TI - Association Between Initial Age of Exposure to Childhood Abuse and Cognitive Control: Preliminary Evidence. AB - Cognitive control, which relies on the protracted development of frontal-parietal regions into adolescence, is a brain process that may be particularly vulnerable to the impact of childhood abuse. In this study, we used functional magnetic resonance imaging (fMRI) to examine associations between the age of onset of childhood abuse and alterations to the neural mechanisms supporting cognitive control in early adulthood, which have not been previously examined. During fMRI scanning, participants completed hybrid block/event-related versions of a classic color-word Stroop task as well as emotional Stroop tasks (threat and positive words). Participants were young adult women (N = 15; age range: 23-30 years) who had a history of childhood physical or sexual abuse that began prior to 13 years of age. Results indicated that earlier age of onset of childhood abuse was robustly associated with increased transient (i.e., event-related) recruitment of medial cognitive control regions in the classic color-word paradigm as well as with less suppression of medial frontal regions that are part of the default mode network, betas = -.16 to -.87. In comparison, increased activation in dorsolateral prefrontal regions was associated with earlier age of abuse onset under conditions of sustained (i.e., blocked) cognitive control in the emotional Stroop task for blocks of positive distracting words versus fixation, betas = .50 to -.60. These results provide preliminary evidence that earlier age of exposure to childhood abuse impacts the functional activation of neural systems involved in cognitive control in adulthood. PMID- 29786894 TI - The Prognostic Role of Phase Angle in Advanced Cancer Patients: A Systematic Review. AB - Phase angle (PA) is a ratio between the reactance and resistance obtained by bioelectric impedance analysis and has been interpreted as a cell membrane integrity indicator and a predictor of total body cell mass. A low PA may suggest deterioration of the cell membrane, which in advanced cancer patients may result in a reduced overall survival (OS). This systematic review sought to investigate the current evidence regarding whether there is an association between PA and OS in patients with advanced cancer (ie, metastatic disease). The search was conducted on electronic databases in August 2017. A total of 34 articles were identified in the initial literature search. Nine studies reporting on 1496 patients were deemed eligible according to our inclusion criteria. PA data were analyzed as continuous variables or according to different cutoffs, under a frequency of 50 Khz. Low PA was associated with worse nutrition status evaluated by body mass index, serum albumin level, transferrin, and fat-free mass. The median OS of the included papers varied from 25.5-330 days, and all studies analyzed showed a significant association between PA and OS, in that patients with low PA had worse OS. Future studies are necessary to justify the use of PA in therapeutic decisions for this population and to evaluate whether nutrition status can influence the association between PA and survival. PMID- 29786895 TI - Deep brain stimulation treated dystonia-trajectory via status dystonicus. AB - BACKGROUND: Status dystonicus (SD) is a life-threatening condition. OBJECTIVE AND METHODS: In a dystonia cohort who developed status dystonicus, we analyzed demographics, background dystonia phenomenology and complexity, trajectory previous to-, via status dystonicus episodes, and evolution following them. RESULTS: Over 20 years, 40 of 328 dystonia patients who were receiving DBS developed 58 status dystonicus episodes. Dystonia was of pediatric onset (95%), frequently complex, and had additional cognitive and pyramidal impairment (62%) and MRI alterations (82.5%); 40% of episodes occured in adults. Mean disease duration preceding status dystonicus was 10.3 +/- 8 years. Evolution time to status dystonicus varied from days to weeks; however, 37.5% of patients exhibited progressive worsening over years. Overall, DBS was efficient in resolving 90% of episodes. CONCLUSION: Status dystonicus is potentially reversible and a result of heterogeneous conditions with nonuniform underlying physiology. Recognition of the complex phenomenology, morphological alterations, and distinct patterns of evolution, before and after status dystonicus, will help our understanding of these conditions. (c) 2018 International Parkinson and Movement Disorder Society. PMID- 29786896 TI - Diagnostic Accuracy of Bioelectrical Impedance Analysis Parameters for the Evaluation of Malnutrition in Patients Receiving Hemodialysis. AB - BACKGROUND: In the absence of a gold standard technique for assessing nutrition status in patients receiving hemodialysis (HD), we aimed to determine the diagnostic accuracy of single-frequency (50 kHz) bioelectrical impedance analysis parameters, resistance/height (R/H), reactance/height (Xc/H), and impedance/height (Z/H), and their cutoff points for malnutrition. METHODS: The reference standards, Subjective Global Assessment (SGA), Malnutrition Inflammation Score, and Nutritional Risk Screening 2002, were performed at baseline and then once a year for 2 years. At least 2 assessments for each reference standard were performed during the monitoring period, and those patients who were assessed as malnourished on at least 2 consecutive occasions were classified as malnourished. RESULTS: A total 101 patients receiving HD were evaluated. R/H and Z/H demonstrated low to moderate accuracy to diagnose malnutrition in men and low accuracy in women, whereas the accuracy of Xc/H was uncertain. The cutoff points of bioelectrical impedance vector analysis (BIVA) parameters, determined based on the SGA to maximize sensitivity and specificity simultaneously, were: R/H >=330.05 and >=420.92 ohms/m for men and women, respectively; Z/H >=332.71 and >=423.19 ohms/m for men and women, respectively. In men, sensitivity based on the cutoff points of R/H and Z/H together ranged from 73% to 89% and specificity ranged from 49% to 50%. In women, sensitivity ranged from 58% to 80% and specificity from 48% to 55%. CONCLUSION: BIVA parameters demonstrated low to moderate accuracy in men and low accuracy in women for the diagnosis of malnutrition. PMID- 29786897 TI - Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias. AB - BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. METHODS: Genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. RESULTS: Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. CONCLUSIONS: Targeted next generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients' care and enable genetic counseling. PMID- 29786898 TI - Adults with Comorbid Posttraumatic Stress Disorder, Alcohol Use Disorder, and Opioid Use Disorder: The Effectiveness of Modified Prolonged Exposure. AB - Opioid use disorders (OUDs) are a growing problem in the United States. When OUDs co-occur with problematic drinking and posttraumatic stress disorder (PTSD), negative drug-related mental and physical health outcomes may be exacerbated. Thus, it is important to establish whether PTSD treatments with established efficacy for dually diagnosed individuals also demonstrate efficacy in individuals who engage in problematic drinking and concurrent opioid misuse. Adults who met DSM-IV-TR criteria for PTSD and alcohol dependence were recruited from a substance use treatment facility and were randomly assigned to receive either modified prolonged exposure (mPE) therapy for PTSD or a non-trauma-focused comparison treatment. Compared to adults in a non-OUD comparison group (n = 74), adults with OUD (n = 52) were younger, reported more cravings for alcohol, were more likely to use amphetamines and sedatives, were hospitalized more frequently for drug- and alcohol-related problems, and suffered from more severe PTSD symptomatology, depressive symptoms, and anxiety, standardized mean differences = 0.36-1.81. For participants with OUD, mPE was associated with large reductions in PTSD symptomatology, sleep disturbances, and symptoms of anxiety and depression, ds = 1.08-2.56. Moreover, participants with OUD reported decreases in alcohol cravings that were significantly greater than those reported by the non-OUD comparison group, F(1, 71.42) = 6.37, p = .014. Overall, our findings support the efficacy of mPE for PTSD among individuals who engage in problematic drinking and concurrent opioid misuse, despite severe baseline symptoms. PMID- 29786899 TI - Improved Stable Indocyanine Green (ICG)-Mediated Cancer Optotheranostics with Naturalized Hepatitis B Core Particles. AB - In recent years, hepatitis B core protein virus-like particle (HBc VLP) is an impressive biomaterial, which has attracted considerable attention due to favorable properties such as structural stability, high uptake efficiency, and biocompatibility in biomedical applications. Heretofore, only a few attempts have been made to apply it in physical, chemical, and biological therapy for cancer. In this study, a tumor-targeting RGD-HBc VLP is first fabricated through genetic engineering. For image-guided cancer phototherapy, indocyanine green (ICG) is loaded into RGD-HBc VLP via a disassembly/reassembly pathway and electrostatic attraction with high efficiency. The self-assembled stable RGD-HBc VLP significantly improves body retention (fourfold longer), aqueous stability, and target specificity of ICG. Remarkably, these positive reformations promote more accurate and sensitive imaging of U87MG tumor, as well as prolonged tumor destruction in comparison with free ICG. Moreover, the photothermal and photodynamic effect on tumors are quantitatively differentiated by multiple linear regression analysis. Overall, less-potent medicinal ICG can be perfectly rescued by bioengineered HBc VLP to realize enhanced cancer optotheranostics. PMID- 29786901 TI - Degradable Polymers and Nanoparticles Built from Salicylic Acid. AB - As more evidence emerges supporting the possibility that nonsteroidal anti inflammatory drugs, especially aspirin (acetyl salicylic acid), might have a role in the prevention and management of certain types of cancer, there have been several attempts to fabricate salicylic acid-based polymers that can be employed in the targeted therapy of tumors. The primary disadvantage so far has been in use of nontherapeutic polymeric backbones that constitute the majority of the therapeutic particle's size. The focus of this research is the creation of a biodegradable polymer consisting only of salicylic acid, and its use as the main building block in targeted nanotherapeutics that would consequently provide both high local dose and sustained release of the active moiety. This work demonstrates the synthesis and degradation of polysalicylates, and modulation of their size and hydrolytic stability through the formation of nanostructures. PMID- 29786902 TI - Engineered Metalloenzymes with Non-Canonical Coordination Environments. AB - Nature employs a limited number of genetically encoded, metal-coordinating residues to create metalloenzymes with diverse structures and functions. Engineered components of the cellular translation machinery can now be exploited to encode non-canonical ligands with user-defined electronic and structural properties. This ability to install "chemically programmed" ligands into proteins can provide powerful chemical probes of metalloenzyme mechanism and presents excellent opportunities to create metalloprotein catalysts with augmented properties and novel activities. In this Concept article, we provide an overview of several recent studies describing the creation of engineered metalloenzymes with interesting catalytic properties, and reveal how characterization of these systems has advanced our understanding of nature's bioinorganic mechanisms. We also highlight how powerful laboratory evolution protocols can be readily adapted to allow optimization of metalloenzymes with non-canonical ligands. This approach combines beneficial features of small molecule and protein catalysis by allowing the installation of a greater variety of local metal coordination environments into evolvable protein scaffolds, and holds great promise for the future creation of powerful metalloprotein catalysts for a host of synthetically valuable transformations. PMID- 29786900 TI - Avian demographic responses to drought and fire: a community-level perspective. AB - Drought stress is an important consideration for wildlife in arid and semiarid regions under climate change. Drought can impact plant and animal populations directly, through effects on their physiology, as well as indirectly through effects on vegetation productivity and resource availability, and by creating conditions conducive to secondary disturbance, such as wildfire. We implemented a novel approach to understanding community-level demographic responses of birds and their habitats to these stressors in the context of climate change at 14 study sites in the Four Corners region of the southwestern United States. A large wildfire affecting three of the sites provided a natural experiment for also examining fire effects on vegetation and the bird community. We assessed (1) trends in drought and end-of-century (2071-2100) predicted average drought conditions under mid-range and high greenhouse gas concentration trajectory scenarios; (2) effects of drought and fire on habitat (vegetation greenness); and (3) effects of drought and fire on community-level avian productivity and adult apparent survival rates. Drought has increased and is expected to increase further at our study sites under climate change. Under spring drought conditions, vegetation greenness and avian productivity declined, while summer drought appeared to negatively affect adult apparent survival rates. Response to fire was mixed; in the year of the fire, avian productivity declined, but was higher than normal for several years post-fire. Our results highlight important links between environmental stressors and avian vital rates that will likely affect population trajectories in this region under climate change. We suggest that the use and continued development of community-level demographic models will provide useful tool for leveraging sparse species-level data to provide multi-species inferences and inform conservation. PMID- 29786903 TI - Copper-Catalyzed Allylic C-H Alkynylation by Cross-Dehydrogenative Coupling. AB - C-H bond functionalization is a well-developed concept that has been thoroughly studied and gives entry to rather complex molecules without the need for previous derivatization of the substrates. The use of copper complexes in allylic C-H bond functionalization under oxidative conditions as an alternative to the well established palladium-based methodologies remains largely underdeveloped. Here, we show for the first time a selective cross-dehydrogenative coupling reaction between underivatized allylic substrates and terminal alkynes to produce 1,4 enynes in high yields in a single step, using an in situ synthesized copper catalyst and an oxidant. PMID- 29786904 TI - Visible Light-Induced Supra-Amphiphilic Switch Leads to Transition from Supramolecular Nanosphere to Nanovesicle Activated by Pillar[5]arene-Based Host Guest Interaction. AB - A photoresponsive host-guest supramolecular complex (WP5?G) constructed by water soluble pillar[5]arene (WP5) and spiropyran derivative (G) is presented. The spontaneous isomerization of G from spiropyran (SP) form to ring-opened merocyanine (MC) form happens either alone or in WP5?G in aqueous media. Irradiated by visible light, G can be converted into SP form completely and the hydrophilicity will be changed. G and WP5?G are both verified to self-assemble into nanospheres. Upon exposure to visible light, WP5?G reassemble into nanovesicles due to the change of supra-amphiphilicity, while G alone does not have this transition. Obviously, WP5 takes the key role that activates the photoinduced morphological transition. PMID- 29786905 TI - Quasi-3D-Structured Interfaces by Polymer Brushes. AB - The fabrication of polymer brushes via surface-initiated controlled radical polymerizations has progressively developed beyond a simple surface functionalization technique, enabling the design of complex polymer interfaces with a quasi-3D molecular organization. The modulation of polymer brush structure has led to an extremely broad tuning potential for technologically relevant interfacial, physicochemical properties, allowing one to precisely tune swelling, nanomechanical, and nanotribological characteristics of polymer films. In addition, the synthesis of multilayer brush interfaces with hierarchical architecture has been exploited to control biological phenomena on modified platforms, such as cell adhesion and settlement, or to fully prevent biological contamination from bacteria. In this feature article, the most recent developments in the synthesis and application of quasi-3D structured polymer brushes are summarized, placing particular attention on how the tuning of grafted polymer architecture could translate into a variation of interfacial characteristics. PMID- 29786906 TI - Reversible C-H Activation, Facile C-B/B-H Metathesis and Apparent Hydroboration Catalysis by a Dimethylxanthene-Based Frustrated Lewis Pair. AB - A dimethylxanthene-based phosphine/borane frustrated Lewis pair (FLP) is shown to effect reversible C-H activation, cleaving phenylacetylene, PhCCH, to give an equilibrium mixture of the free FLP and phosphonium acetylide in CD2 Cl2 solution at room temperature. This system also reacts with B-H bonds although in a different fashion: reactions with HBpin and HBcat proceed via C-B/B-H metathesis, leading to replacement of the -B(C6 F5 )2 Lewis acid component by -Bpin/-Bcat, and transfer of HB(C6 F5 )2 to the phosphine Lewis base. This transformation underpins the ability of the FLP to catalyze the hydroboration of alkynes by HBpin: the active species is derived from the HB(C6 F5 )2 fragment generated in this exchange process. PMID- 29786907 TI - Simulation of the Degradation of Cyclic Ketene Acetal and Vinyl-Based Copolymers Synthesized via a Radical Process: Influence of the Reactivity Ratios on the Degradability Properties. AB - The radical copolymerization of vinyl and cyclic ketene acetal (CKA) monomers is a promising way to prepare degradable vinyl polymers. The reactivity of the comonomer pair is known to be dependent of the vinyl monomer structure that requires to play with experimental conditions (feed ratio, overall monomer conversion, etc.) to target a desired cumulative (average) copolymer composition. Even if the materials are completely degradable, there is no information about the homogeneity of the degraded products. This theoretical study, using kinetic Monte Carlo simulations, allows simulating degradation at the molecular level. It is shown that disparate reactivity ratios (styrene/CKA, etc.) and also a composition drift at high conversion can lead to an inhomogeneous degraded product compared to systems with similar reactivity ratios (vinyl ether/CKA, etc.). The use of reversible deactivation radical polymerization techniques does not influence the final degraded products and is only useful for the design of advanced macromolecular architectures before degradation. PMID- 29786908 TI - Opposing patterns of intraspecific and interspecific differentiation in sex chromosomes and autosomes. AB - Linking intraspecific and interspecific divergence is an important challenge in speciation research. X chromosomes are expected to evolve faster than autosomes and disproportionately contribute to reproductive barriers, and comparing genetic variation on X and autosomal markers within and between species can elucidate evolutionary processes that shape genome variation. We performed RADseq on a 16 population transect of two closely related Australian cricket species, Teleogryllus commodus and T. oceanicus, covering allopatry and sympatry. This classic study system for sexual selection provides a rare exception to Haldane's rule, as hybrid females are sterile. We found no evidence of recent introgression, despite the fact that the species coexist in overlapping habitats in the wild and interbreed in the laboratory. Putative X-linked loci showed greater differentiation between species compared with autosomal loci. However, population differentiation within species was unexpectedly lower on X-linked markers than autosomal markers, and relative X-to-autosomal genetic diversity was inflated above neutral expectations. Populations of both species showed genomic signatures of recent population expansions, but these were not strong enough to account for the inflated X/A diversity. Instead, most of the excess polymorphism on the X could better be explained by sex-biased processes that increase the relative effective population size of the X, such as interspecific variation in the strength of sexual selection among males. Taken together, the opposing patterns of diversity and differentiation at X versus autosomal loci implicate a greater role for sex-linked genes in maintaining species boundaries in this system. PMID- 29786909 TI - A New Composite Electrode Applied for Studying the Electrochemistry of Insoluble Particles: alpha-HgS. AB - The redox chemistry of solid alpha-HgS particles is revealed using a carbon/PVDF composite containing alpha-HgS, carbon black, polyvinylidene fluoride (PVDF). The electrochemical behaviour of the carbon/PVDF composite is first characterised with three water insoluble organic solids. Then the reduction of solid alpha-HgS particles is investigated and found to occur at a high negative potential, -1.82 V versus saturated mercury sulphate reference electrode, to form metallic mercury and sulphide ions. The subsequent oxidation of metallic mercury and sulphide occurs at +0.24 and -0.49 V versus MSE respectively. PMID- 29786910 TI - Agathisflavone isolated from Anacardium occidentale suppresses SIRT1-mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe-transfected SH SY5Y cells. AB - Agathisflavone is a bioactive compound in Anacardium occidentale. In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH SY5Y cells. Experiments in lipopolysaccharide (LPS)-activated BV2 microglia showed that pretreatment with agathisflavone (5-20 MUM) produced significant reduction in the release of tumour necrosis factor-alpha, interleukin-6, interleukin-1beta, NO, and PGE2 from the cells. Immunoblotting experiments also revealed that agathisflavone reduced levels of iNOS and COX-2 protein. Further studies revealed that agathisflavone reduced neuroinflammation by targeting critical steps in NF-kappaB signalling in BV2 microglia. Treatment of SH-SY5Y cells with conditioned medium from LPS-activated BV2 microglia produced a significant reduction in neuronal viability. However, conditioned medium from BV2 cells that were stimulated with LPS in the presence of agathisflavone did not induce neurotoxicity. Agathisflavone also produced neuroprotection in APPSwe plasmid-transfected SH-SY5Y neurons. The compound further attenuated LPS-induced and APPSwe plasmid-induced reduction in SIRT1 in BV2 microglia and SH-SY5Y, respectively. In the presence of EX527, agathisflavone lost its anti-inflammatory and neuroprotective activities. Our results suggest that agathisflavone inhibits neuroinflammation in BV2 microglia by targeting NF-kappaB signalling pathway. The compound also reduces neurotoxicity through mechanisms that are possibly linked to SIRT1 in the microglia and neurons. PMID- 29786912 TI - Ylide Ligands as Building Blocks for Bioactive Group 11 Metal Complexes. AB - The reactivity of the phosphonium salt (cyanomethyl)triphenylphosphonium chloride and the ylide (triphenylphosphonio)cyanomethanide towards Group 11 metal complexes is described. Mononuclear neutral gold(I) and gold(III) complexes of the type [AuX{CH(CN)PPh3 }] or [AuX3 {CH(CN)PPh3 }] and cationic derivatives such as [AuL{CH(CN)PPh3 }]X have been prepared. Surprisingly, the cationic gold species could only be prepared with ligands with a large steric hindrance, such as bulky NHCs or the JohnPhos phosphine, in contrast to silver and copper derivatives, which have dimeric structures through the coordination of the metal to the cyano group of the ylide of a second complex. Bis(ylide) metal complexes have also been synthesised in which a different structure is observed for the gold complexes compared with the copper and silver complexes. Although gold forms mononuclear species, the silver complex presents a two-dimensional polymeric structure as a result of further coordination of the silver centre to the nitrogen atoms of cyano groups of further silver complexes. These complexes possess two chiral centres; the gold compound was obtained as a mixture of diastereoisomers, whereas the copper and silver derivatives afford only one diastereoisomer. These compounds were screened for their in vitro cytotoxic activity against the human lung carcinoma cell line (A549). The IC50 values reveal an excellent cytotoxic activity for these metal complexes compared with cisplatin. PMID- 29786911 TI - ESIPT-Modulated Emission of Lanthanide Complexes: Different Energy-Transfer Pathways and Multiple Responses. AB - Two series of isostructural lanthanide coordination complexes, namely, LIFM 42(Ln) (Ln=Eu, Tb, Gd, in which LIFM stands for the Lehn Institute of Functional Materials) and LIFM-43(Ln) (Ln=Er, Yb), were synthesized through the self assembly of an excited-state intramolecular proton transfer (ESIPT) ligand, 5-[2 (5-fluoro-2-hydroxyphenyl)-4,5-bis(4-fluorophenyl)-1H-imidazol-1-yl]isophthalic acid (H2 hpi2cf), with different lanthanide ions. In the coordination structures linked by the ligands and oxo-bridged LnIII2 clusters (for LIFM-42(Ln) series) or isolated LnIII ions (for LIFM-43(Ln) series), the ESIPT ligand can serve as both the host and antenna for protecting and sensitizing the photoluminescence (PL) of LnIII ions. Meanwhile, the -OH???N active sites on the ligands are vacant, which provides availability to systematically explore the PL behavior of Ln complexes with ESIPT interference. Based on the accepting levels of different lanthanide ions, energy transfer can occur from the T1 (K*) or T1 (E*) (K*=excited keto form, E*=excited enol form) excited states of the ligand. Furthermore, the sensitized lanthanide luminescence in both visible and near-infrared regions, as well as the remaining K* emission of the ligand, can be modulated by the ESIPT responsiveness to different solvents, anions, and temperature. PMID- 29786913 TI - New Insights into the Anion Transport Selectivity and Mechanism of Tren-based Tris-(thio)ureas. AB - The anion transport properties of a series of previously reported tren-based anionophores have been revisited using new assays designed to measure anion uniport. This study provides new insights into the transport mechanism and selectivity of this important class of transporters. Specifically, we report the chloride and nitrate transport selectivity of these systems and quantify sulfate transport to determine EC50 values for sulfate transport for the first time. Two new assays were developed to study bicarbonate transport allowing accurate quantification of chloride/bicarbonate exchange. PMID- 29786914 TI - Conductive Hydrogels as Smart Materials for Flexible Electronic Devices. AB - Flexible conductive materials have gained considerable research interest in recent years because of their potential applications in flexible energy storage devices, sensors, touch panels, electronic skins, etc. With excellent flexibility, outstanding electric properties and tunable mechanical properties, conductive hydrogels as conductive materials offer plentiful insights and opportunities for flexible electronic devices. Numerous synthetic strategies have been developed to obtain various conductive hydrogels, and high-performance flexible electronic devices based on these conductive hydrogels have been realized. This review provides a comprehensive overview of conductive-hydrogel based flexible electronics, ranging from conductive hydrogels synthesis to several important flexible devices applications, including touch panels, sensors and energy storage. Finally, we provide new future research directions and perspectives for conductive-hydrogel-based flexible and portable electronic devices. PMID- 29786915 TI - Reversible Oxidative Addition/Reductive Elimination of a Si-H Bond with Base Stabilized Silylenes: A Theoretical Insight. AB - Although oxidative addition (OA) and reductive elimination (RE) are exceedingly important processes in organometallic chemistry, such processes are still extremely rare for main-group element species. Herein, we report a theoretical study on the reaction of phosphine-stabilized silylenes with silanes that proceeds through reversible OA/RE at room temperature. Of particular interest is that this theoretical approach highlights the important role of the ligand, which can greatly affect the kinetics and energy balance of the reaction. Indeed, in contrast to the case of free aminosilylenes, the reaction of ligand-supported silylenes proceeds in an unsynchronized manner and starts with the silylene >silane charge transfer (CT). Suitably electron-donating ligands, such as phosphines or N-heterocyclic carbenes, enhancing the CT at the transition state (TS), significantly decrease the Gibbs activation energy and the exergonic nature of the reaction, which promote the OA/RE processes. In the same way, silanes with electron-withdrawing groups also favor the CT and thus stabilize the TS. It was also computationally predicted that phosphine-stabilized silylenes should be able to activate the C-Si bond of trimethoxy(ethynyl)silane (HC=C-Si(OMe)3 ) and that the reaction should proceed in a reversible manner under mild conditions. PMID- 29786916 TI - Herbal medicine as a promising therapeutic approach for the management of vascular dementia: A systematic literature review. AB - Vascular dementia (VaD) generally refers to memory deficits and cognitive abnormalities that are resulted from vascular disease. In this study, we aimed to systematically review the literature wherein therapeutic effects of medicinal plants have been studied on VaD. A systematic literature search was performed in the PubMed, Scopus, Web of Science, Google Scholar, and other databases using VaD, and medicinal plants as key terms. No strict inclusion criteria were defined, and almost all clinical studies were included. A total of 524 articles were found, of which only 28 relevant articles with 3461 studied patients were included to this systematic review. The results showed that medicinal plants, particularly Sancaijiangtang and Ginkgo biloba could improve behavioral and psychological symptoms, working memory, Mini-Mental State Examination, and activities of daily living as well as neuropsychiatric features. It was also shown that the age, average progression of the disease, and the type of folk medicines effective in treating the disease are important factors in the management of VaD. The results of this review indicated that herbal therapy can be a potential candidate in the treatment of VaD; however, further studies are needed to confirm such efficiency. PMID- 29786917 TI - A Strategy of "Self-Isolated Enhanced Emission" to Achieve Highly Emissive Dual State Emission for Organic Luminescent Materials. AB - Currently, the commonly developed organic luminescent materials (OLMs) usually exhibit poor luminescent performance in aggregated solid states compared with their well-dissolved solution states, making it a tough goal to achieve the highly emissive dual-state emission. To overcome this limitation, a "self isolated enhanced emission" (SIEE) strategy through flexible alkyl chains to suppress the emission-quenched pi-pi stacking in solids is proposed here and, based on this guideline, remarkable emission efficiency with photoluminescence quantum yields up to 99.72 % in solution and 77.46 % in the solid state are achieved for the SIEE constructed DBBT-C8, which is then successfully used in solid-state displays and data encryption. PMID- 29786919 TI - International collaboration is needed to reduce the risk for inhibitors in PUPs with severe haemophilia A. PMID- 29786918 TI - Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission. AB - BACKGROUND: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVE: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. RESULTS: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 * 10-7 ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. CONCLUSIONS AND CLINICAL RELEVANCE: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13. PMID- 29786920 TI - Functional Carbon Nanofibers with Semi-Embedded Titanium Oxide Particles via Electrospinning. AB - The formulation of optoelectronic components into 1D nanostructures allows the promotion of new materials with multifunctionalities. In this work, it is demonstrated that new synthesis of photocatalytic carbon nanofiber decorated with semi-embedded titanium oxide (TiO2 ), namely, TiO2 @carbon fiber, is conveniently accessed through the electrospinning of polyacrylonitrile polymer and TiO2 particle comixture, and then followed by photon-activated self-erosion to expose the embedded TiO2 and carbonization. The hybrid nanofibers are characterized by field emission scanning electron microscopy, transmission electron microscopy, and X-ray diffraction analysis. Furthermore, the photocatalytic activities of the resultant fibers are tested with photodegradation of Rhodamine B in aqueous solution, which reveals that the carbon nanofiber with semi-embedded TiO2 drastically improved catalytic efficiency and recyclability, comparing to those fibers without or with embedded TiO2 . PMID- 29786921 TI - Room-Temperature Ferroelectricity in an Organic Cocrystal. AB - Ferroelectric materials exhibit switchable remanent polarization due to reversible symmetry breaking under an applied electric field. Previous research has leveraged temperature-induced neutral-ionic transitions in charge-transfer (CT) cocrystals to access ferroelectrics that operate through displacement of molecules under an applied field. However, displacive ferroelectric behavior is rare in organic CT cocrystals and achieving a Curie temperature (TC ) above ambient has been elusive. Here a cocrystal between acenaphthene and 2,3,5,6 tetrafluoro-7,7,8,8-tetracyanoquinodimethane is presented that shows switchable remanent polarization at room temperature (TC =68 degrees C). Raman spectroscopy, X-ray diffraction, and solid-state NMR spectroscopy indicate the ferroelectric behavior is facilitated by acenaphthene (AN) rotation, deviating from conventional design strategies for CT ferroelectrics. These findings highlight the relevance of non-CT interactions in the design of displacive ferroelectric cocrystals. PMID- 29786923 TI - Biodiversity of the human oral mycobiome in health and disease. AB - The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high-throughput sequencing such as next-generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral cohabitues. Their diversity is perplexing, and functionality yet to be deciphered. Here, we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives. PMID- 29786922 TI - Finding factors that predict treatment-resistant depression: Results of a cohort study. AB - BACKGROUND: Treatment for depressive disorders often requires subsequent interventions. Patients who do not respond to antidepressants have treatment resistant depression (TRD). Predicting who will develop TRD may help healthcare providers make more effective treatment decisions. We sought to identify factors that predict TRD in a real-world setting using claims databases. METHODS: A retrospective cohort study was conducted in a US claims database of adult subjects with newly diagnosed and treated depression with no mania, dementia, and psychosis. The index date was the date of antidepressant dispensing. The outcome was TRD, defined as having at least three distinct antidepressants or one antidepressant and one antipsychotic within 1 year after the index date. Predictors were age, gender, medical conditions, medications, and procedures 1 year before the index date. RESULTS: Of 230,801 included patients, 10.4% developed TRD within 1 year. TRD patients at baseline were younger; 10.87% were between 18 and 19 years old versus 7.64% in the no-TRD group, risk ratio (RR) = 1.42 (95% confidence interval [CI] 1.37-1.48). TRD patients were more likely to have an anxiety disorder at baseline than non-TRD patients, RR = 1.38 (95% CI 1.35-1.14). At 3.68, fatigue had the highest RR (95% CI 3.18-4.25). TRD patients had substance use disorders, psychiatric conditions, insomnia, and pain more often at baseline than non-TRD patients. CONCLUSION: Ten percent of subjects newly diagnosed and treated for depression developed TRD within a year. They were younger and suffered more frequently from fatigue, substance use disorders, anxiety, psychiatric conditions, insomnia, and pain than non-TRD patients. PMID- 29786924 TI - Reproductive ecology of Ocotea catharinensis, an endangered tree species. AB - Ocotea catharinensis (Lauraceae) is an endangered tree species from the Brazilian Atlantic Rainforest. Currently, little is known about the reproductive ecology of this species. Aiming to propose conservation measures, we described aspects related to phenology, floral biology, pollination, seed dispersal and mating system of O. catharinensis. We conducted phenological observations in 62 individuals for 2 years. In one reproductive event, we evaluated nectar production, stigmatic receptivity and pollen viability. Floral visitors were observed, identified and classified on a scale of pollination effectiveness. Seed dispersers were observed and identified using camera traps. Finally, the mating system was evaluated through pollen/ovule ratios, experimental pollination treatments and genetic analysis with molecular markers. Ocotea catharinensis presented a supra-annual fruiting pattern with a substantial reduction of reproducing individuals from bud phase to ripe fruit phase. Several mechanisms prompting cross-fertilisation were identified, such as attractive, herkogamic and protogynic flowers. The main floral visitors and pollinators were from the Diptera order, and all seed dispersers were birds. The species presented a predominantly outcrossed mixed mating system with significant selfing rate (17.3%). Although based on restricted evidence, we hypothesised that selfing is an escape mechanism for situations unfavourable to cross-fertilisation. Specifically, for the studied population selfing is a response to reduced population size, which is caused by the non-reproduction of all potentially reproductive individuals and by past exploitation events. Therefore, conservation efforts should be able to enhance population sizes, as well as prevent overexploitation. PMID- 29786925 TI - Computed tomographic and radiographic bronchial collapse may be a normal characteristic of forced expiration in dogs. AB - Tracheobronchomalacia has been diagnosed using radiography or bronchoscopy to confirm bronchial changes in luminal diameter during the respiratory cycle. However, studies in healthy humans suggest that some degree of bronchial collapse may be observed during the normal respiratory cycle. In this analytical study, the luminal diameter of the bronchus to each of the six pulmonary lobes and the mean percentage of expiratory collapse from end inspiratory, end expiratory, and two forced expiratory phases (10 and 15 ml/kg) were determined via computed tomography (CT) and radiography in 22 healthy Beagle dogs. The bronchial collapsibility was significantly greater during the forced expiration than the end expiration (P < 0.001); the same results were observed in dorsal and sagittal CT images and radiographs (P < 0.001). Median collapsibility values associated with 15 ml/kg forced expiratory collapse determined via cross-sectional CT images were measured as 16.6-45.5% and differed according to the pulmonary lobe. Median collapsibilities on radiography with 15 ml/kg forced expiration were 57.8% and 62.1% in the right cranial lobe and right caudal lobe, respectively. In conclusion, bronchial diameter may change during the respiratory cycle, and some degree of reduction in bronchial diameter may be an incidental finding in healthy dogs. More rigorous criteria are needed with regards to bronchial collapsibility during normal respiration for the diagnosis of bronchomalacia in order to avoid false-positive diagnoses. PMID- 29786926 TI - Thorpe-Ingold Effect in Branch-Selective Alkylation of Unactivated Aryl Fluorides. AB - Presented herein is a general protocol for the alkylation of simple aryl fluorides with unbiased secondary Grignard reagents by means of nickel catalysis. This study revealed a general Thorpe-Ingold effect in the ligand backbone which confers a high degree of selectivity for the secondary carbon center in the C-C coupling event. This protocol is characterized by mild reaction conditions, robustness, and simplicity. Both electron-rich and electron-deficient aryl fluorides are suitable candidates in this transformation. Equally amenable are a variety of heterocycles, permitting the coupling without over alkylation at the electrophilic sites. PMID- 29786927 TI - Exhaled nitric oxide and mannitol test to predict exercise-induced bronchoconstriction. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is diagnosed via exercise challenge on a treadmill, but such testing requires complex equipment and sufficient health-care resources. The fraction of exhaled nitric oxide (FeNO) test and mannitol bronchial provocation test (BPT) may serve as a surrogate for exercise testing. METHODS: We compared the diagnostic utilities of the FeNO test and mannitol BPT in predicting EIB in asthmatic children. We retrospectively analyzed data from 60 asthmatic children aged 6-16 years. We compared the exercise BPT results, FeNO levels, and mannitol BPT data. RESULTS: All subjects were divided into exercise-positive (n = 41) or -negative (n = 19) BPT groups. Of the 41 exercise-positive patients, 32 were mannitol BPT positive and nine were mannitol BPT negative. Of the 19 exercise-negative patients, nine and 10, respectively, were mannitol BPT positive and BPT negative. The maximum % forced expiratory volume in 1 s (FEV1 ) decrease after exercise was positively correlated with FeNO (r = 0.556, P < 0.001), and with mannitol response-dose ratio (RDR; r = 0.416, P = 0.001). The receiver operating characteristic (ROC) curve for FeNO to discriminate between asthmatic subjects with and without EIB had an area under the curve (AUC) of 0.771 (95%CI: 0.643-0.870). The discriminatory ROC curve for mannitol RDR had an AUC of 0.763 (95%CI: 0.633 0.864). The AUC of FeNO and mannitol RDR did not differ significantly. CONCLUSIONS: EIB significantly correlated with both FeNO and mannitol BPT data. Given that both methods similarly predicted EIB in asthmatic children, the simpler and safer FeNO test alone may be a clinically useful diagnostic tool. PMID- 29786928 TI - Evaluation of medication dose omissions amongst inpatients in a hospital using an electronic Medication Management System. AB - RATIONALE, AIMS, AND OBJECTIVES: Whilst many dose omissions cause no patient harm, inappropriate dose omissions have been associated with increased length of hospital stay, risk of sepsis, and mortality. This study aimed to comprehensively describe the prevalence and nature of omitted doses overall and of high risk medication dose omissions in an organization using an electronic Medication Management System. METHODS: A retrospective cross-sectional study was undertaken in an Australian tertiary referral health service. All routinely documented electronic inpatient dose administration records from 1st July 2014 to 30th June 2015 were included. Period prevalence and characteristics of dose omissions overall and of high-risk medication dose omissions were determined. RESULTS: During the study period, 3.3 million inpatient doses were scheduled for administration, with doses endorsed as "not given" comprising 6.2% of all scheduled doses. Non-valid dose omissions (medication not available or no justification documented) comprised 1.2% of scheduled doses. Patient refusal accounted for one third of all dose omissions, while for 12% no explanation was provided and 7% were endorsed "medication not available". High-risk medications accounted for 20% of all dose omissions. One in 20 antimicrobial doses scheduled were omitted, and of these, 17% were due to patient refusal. CONCLUSION: The period prevalence of dose omissions in this large study after electronic Medication Management System implementation is similar to that found when paper charts were used. Although most dose omissions appear appropriate, many orders were not given due to patient refusal or with no documented justification. Interventions to minimize unintentional dose omissions are indicated. PMID- 29786929 TI - Rethinking the prescription of biotin for dermatologic conditions. PMID- 29786930 TI - An Unexpected alpha-Oxidation of Cyclic Ketones with 1,4-Benzoquinone by Enol Catalysis. AB - The first direct and asymmetric alpha-aryloxylation of cyclic ketones via enol catalysis has been achieved using quinones as the reaction partners. Catalytic amounts of a phosphoric acid promote the exclusive formation of alpha,alpha disubstituted ketones from the corresponding alpha-substituted ketones in good yields and enantioselectivities (up to 96.5:3.5 er). Preliminary mechanistic experiments suggest that this reaction proceeds via a proton-coupled electron transfer (PCET) followed by radical recombination. PMID- 29786932 TI - Bandgap-Tunable Preparation of Smooth and Large Two-Dimensional Antimonene. AB - As a highly stable band gap semiconductor, antimonene is an intriguing two dimensional (2D) material in optoelectronics. However, its short layer distance and strong binding energy make it challenging to prepare high-quality large 2D antimonene; therefore, its predicted tunable band gap has not been experimentally confirmed. Now, an approach to prepare smooth and large 2D antimonene with uniform layers that uses a pregrinding and subsequent sonication-assisted liquid phase exfoliation process has been established. Mortar pregrinding provides a shear force along the layer surfaces, forming large, thin antimony plates, which can then easily be exfoliated into smooth, large antimonene, avoiding long sonication times and antimonene destruction. The resulting antimonene also enabled verification of the tunable band gap from 0.8 eV to 1.44 eV. Hole extraction and current enhancement by about 30 % occurred when the antimonene was used as a hole transport layer in perovskite solar cells. PMID- 29786931 TI - Direct Real-Time Monitoring of Prodrug Activation by Chemiluminescence. AB - The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by beta-galactosidase. The activation of the prodrug in the presence of beta-galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses beta-galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in beta-galactosidase-overexpressing tumor-bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment. PMID- 29786933 TI - Acute generalized exanthematous pustulosis due to terbinafine. AB - Acute generalized exanthematous pustulosis is a rare adverse cutaneous reaction characterized by the rapid appearance of numerous pustules arising on edematous, erythematous skin. It is commonly accompanied by fever and leukocytosis and usually resolves with discontinuation of the offending agent. Herein, acute generalized exanthematous pustulosis induced by terbinafine is described, followed by a brief review of the literature. PMID- 29786934 TI - The Origin of the Photoluminescence Enhancement of Gold-Doped Silver Nanoclusters: The Importance of Relativistic Effects and Heteronuclear Gold Silver Bonds. AB - The weak photoluminescence of silver nanoclusters prevents their broad application as luminescent nanomaterials. Recent experiments, however, have shown that gold doping can significantly enhance the photoluminescence intensity of Ag29 nanoclusters but the molecular and physical origins of this effect remain unknown. Therefore, we have computationally explored the geometric and electronic structures of Ag29 and gold-doped Ag29-x Aux (x=1-5) nanoclusters in the S0 and S1 states. We found that 1) relativistic effects that are mainly due to the Au atoms play an important role in enhancing the fluorescence intensity, especially for highly doped Ag26 Au3 , Ag25 Au4 , and Ag24 Au5 , and that 2) heteronuclear Au-Ag bonds can increase the stability and regulate the fluorescence intensity of isomers of these gold-doped nanoclusters. These novel findings could help design doped silver nanoclusters with excellent luminescence properties. PMID- 29786936 TI - A General Synthesis of Phosphorus- and Arsenic-Containing Analogues of the Thio- and Seleno-cyanate Anions. AB - A general synthetic protocol for the synthesis of phosphorus- and arsenic containing analogues of the thio- and seleno-cyanate anions is reported. This procedure allows for the isolation of three unprecedented species: the phosphaethynselenolate, PCSe- (1), the arsaethynthiolate, AsCS- (2), and the arsaethynselenolate, AsCSe- (3), anions. The structures, electronic properties, and spectroscopic signatures of these species are reported. PMID- 29786935 TI - Evaluation of PCR primers targeting the groEL gene for the specific detection of Streptococcus agalactiae in the context of aquaculture. AB - AIMS: The aim of this study was to design a set of primers for specific detection and identification of Streptococcus agalactiae in polymerase chain reaction (PCR) that can detect a diverse range of S. agalactiae isolates from different hosts and that it is capable of discriminating between S. agalactiae and other species that are closely related or potentially present in aquaculture environments, notably Streptococcus iniae. METHODS AND RESULTS: Primers, based on the groEL2 gene of S. agalactiae, were shown to be epidemiologically sensitive to 97 isolates of S. agalactiae, representing 11 clonal complexes derived from piscine, terrestrial and aquatic mammalian host species. The primers were tested with 10 S. iniae isolates and 22 other comparator species with no cross-reaction observed after optimization of reaction conditions. They have a high analytical sensitivity, detecting as few as 10 copies of S. agalactiae genomic DNA per reaction and are capable of detecting the target in DNA extracted from the brains of infected fish. CONCLUSIONS: The primers proved suitable for the sensitive and specific detection of S. agalactiae from dairy-, human- and fish-related origins by PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to the importance of S. agalactiae as a pathogen, many PCR primers have been published for this bacterium, designed largely for its detection in dairy and human samples, but many cross-reacting with S. iniae. The ability to differentiate between S. agalactiae and S. iniae in aquaculture derived samples is important as both infect fish, causing similar disease symptoms and are phenotypically similar, yet control strategies and zoonotic risk are species specific. PMID- 29786937 TI - The effect of the weekend upon admissions to General Medicine. AB - RATIONALE, AIMS, AND OBJECTIVES: A reduction in the provision of hospital services on the weekend probably explains higher mortality for patients who are either admitted to hospital or undergo procedures on the weekend. The aim was to examine the effect of the day of the week of admission (DOWOA) upon the efficiency and quality of care for a cohort of General Medical inpatients. METHODS: Electronic records were selected for unplanned adult admissions to 2 large public hospitals in Adelaide, South Australia, July 2012 to June 2017. RESULTS: The cohort consisted of 50 323 records. The number of admissions on each day of the week differed significantly from 6389 on Sundays to 7548 on Thursdays (P < 0.001). Discharges were most frequent on Fridays, and fewest occurred on weekends (P < 0.001) especially if aged over 80 years, if they had significant comorbidity or if they were discharged to a residential aged care facility. The DOWOA did not significantly influence the proportion of cases who died in hospital (5.6% to 6.4%; P = 0.47). The DOWOA significantly affected median inpatient length of stay (IPLOS; 3.1 to 3.9 days; P < 0.001). The median inpatient length of stay (IPLOS) matched the number of days from the ensuing weekend to the DOWOA with the longest median IPLOS. CONCLUSIONS: General Medicine has an inpatient mortality unaffected by the DOWOA. Care efficiency, however, follows a weekly cycle. The "weekend effect" for General Medical inpatients is a prolongation in their IPLOS as a result of fewer weekend discharges. PMID- 29786938 TI - Inhibition and kinetic studies of lignin degrading enzymes of Ganoderma boninense by naturally occurring phenolic compounds. AB - AIM: Lignolytic (lignin degrading) enzyme, from oil palm pathogen Ganoderma boninense Pat. (Syn G. orbiforme (Ryvarden)), is involved in the detoxification and the degradation of lignin in the oil palm and is the rate-limiting step in the infection process of this fungus. Active inhibition of lignin-degrading enzymes secreted by G. boninense by various naturally occurring phenolic compounds and estimation of efficiency on pathogen suppression was aimed at. METHODS AND RESULTS: In our work, 10 naturally occurring phenolic compounds were evaluated for their inhibitory potential towards the lignolytic enzymes of G. boninense. Additionally, the lignin-degrading enzymes were characterized. Most of the peholic compounds exhibited an uncompetitive inhibition towards the lignin degrading enzymes. Benzoic acid was the superior inhibitor to the production of lignin-degrading enzymes, when compared between the 10 phenolic compounds. The inhibitory potential of the phenolic compounds towards the lignin-degrading enzymes are higher than that of the conventional metal ion inhibitor. The lignin degrading enzymes were stable in a wide range of pH but were sensitive to higher temperature. CONCLUSION: The study demonstrated the inhibitor potential of 10 naturally occurring phenolic compounds towards the lignin-degrading enzymes of G. boninense with different efficacies. SIGNIFICANCE AND IMPACT OF THE STUDY: The study has shed a light towards a new management strategy to control basal stem rot disease in oil palm. It serves as a replacement for the existing chemical control. PMID- 29786939 TI - An update on enzymatic cocktails for lignocellulose breakdown. AB - Alternative energy sources have received increasing attention in recent years. The possibility of adding value to agricultural wastes, by producing biofuels and other products with economic value from lignocellulosic biomass by enzymatic hydrolysis, has been widely explored. Lignocellulosic biomass, as well as being an abundant residue, is a complex recalcitrant structure that requires a consortium of enzymes for its complete degradation. Pools of enzymes with different specificities acting together usually produce an increase in hydrolysis yield. Enzymatic cocktails have been widely studied due to their potential industrial application for the bioconversion of lignocellulosic biomass. This review presents an overview of enzymes required to degrade the plant cell wall, paying particular attention to the latest advances in enzymatic cocktail production and the main results obtained with cocktails used to degrade a variety of types of biomass, as well as some future perspectives within this field. PMID- 29786940 TI - Glycoinformatics: Bridging Isolated Islands in the Sea of Data. AB - Glycoinformatics is an actively developing scientific discipline, which provides scientists with the means of access to the data on natural glycans and with various tools of their processing. However, the informatization of glycomics has a long way to go before catching up with genomics and proteomics. In this Viewpoint, we review the current situation in glycoinformatics and discuss its achievements and shortcomings, emphasizing the major drawbacks: the lack of recognized standards, protocols, data indices and tools, and the informational isolation of the existing projects. We reiterate possible solutions of the persistent issues and describe our vision of an ideal glycoinformatics project. PMID- 29786941 TI - A Regio- and Diastereoselective Anodic Aryl-Aryl Coupling in the Biomimetic Total Synthesis of (-)-Thebaine. AB - The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)-reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired regioisomers. Electrochemistry would represent a sustainable alternative in this respect but all attempts to accomplish an electrochemical synthesis of thebaine have failed so far. Herein, a regio- and diastereoselective anodic coupling of 3',4',5' trioxygenated laudanosine derivatives is presented, which finally enables electrochemical access to (-)-thebaine. PMID- 29786942 TI - Jose-Miguel Barea 1942-2018: the man that always smiles. PMID- 29786943 TI - Integrating a comprehensive DNA barcode reference library with a global map of yews (Taxus L.) for forensic identification. AB - Rapid and accurate identification of endangered species is a critical component of biosurveillance and conservation management, and potentially policing illegal trades. However, this is often not possible using traditional taxonomy, especially where only small or preprocessed parts of plants are available. Reliable identification can be achieved via a comprehensive DNA barcode reference library, accompanied by precise distribution data. However, these require extensive sampling at spatial and taxonomic scales, which has rarely been achieved for cosmopolitan taxa. Here, we construct a comprehensive DNA barcode reference library and generate distribution maps using species distribution modelling (SDM), for all 15 Taxus species worldwide. We find that trnL-trnF is the ideal barcode for Taxus: It can distinguish all Taxus species and in combination with ITS identify hybrids. Among five analysis methods tested, NJ was the most effective. Among 4,151 individuals screened for trnL-trnF, 73 haplotypes were detected, all species-specific and some population private. Taxonomical, geographical and genetic dimensions of sampling strategy were all found to affect the comprehensiveness of the resulting DNA barcode library. Maps from SDM showed that most species had allopatric distributions, except T. mairei in the Sino Himalayan region. Using the barcode library and distribution map data, two unknown forensic samples were identified to species (and in one case, population) level and another was determined as a putative interspecific hybrid. This integrated species identification system for Taxus can be used for biosurveillance, conservation management and to monitor and prosecute illegal trade. Similar identification systems are recommended for other IUCN- and CITES listed taxa. PMID- 29786944 TI - Design, synthesis and evaluation of a novel series of inhibitors reversing P glycoprotein-mediated multidrug resistance. AB - Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells. Compound 19 also played an important role in the P-gp efflux function of intracellular Rh123 and doxorubicin (DOX) accumulation in K562/A02 cells. Moreover, compound 19 exhibited a long lifetime of approximately 24 hr. These results indicated that compound 19 is a potential lead compound for the design of new drugs to overcome cancer MDR. PMID- 29786945 TI - A comparative study of dietary habits and nutritional intakes among Korean adults according to current depression status. AB - INTRODUCTION: Data regarding the association between depression and dietary factors in Korean adults are limited. We hypothesized that Korean men and women with depression would have poorer nutritional intakes and different dietary habits than those without depression. METHODS: This study was based on data from the Korea National Health and Nutrition Examination Survey conducted during 2012 to 2014. Overall, 10 591 subjects (4308 men, 6529 women) aged 19 to 64 years were selected and categorized according to current depression status. Food and nutrient intakes were estimated using semi-quantitative food frequency questionnaires. RESULTS: Compared with non-depression, depression was associated with a higher body mass index and likelihood of a separated/divorced/widowed status, in addition to lower physical activity and employment rates. After adjusting for multiple variables, men with depression had lower intakes of rice cakes (P = 0.017) and eggs (P = 0.039) and a higher intake of chocolate (P = 0.040) than their non-depressed counterparts. Women with depression had a higher intake of carbonated drinks than those without depression (P = 0.015). However, the groups did not differ significantly in terms of nutrient intakes. A multivariable logistic regression analysis of dietary habits showed that depression correlated inversely with eating out (>=1 time/day vs <1 time/month) among men [odds ratio (OR) = 0.23, 95% confidence interval (CI): 0.10-0.55] and women (OR = 0.14, 95% CI: 0.05-0.35) and positively with a lower number of daily meals (<3 vs >=3) among women (OR = 1.45, 95% CI: 1.01-2.11). DISCUSSION: Current depression status was associated with differences in some specific dietary intakes and habits in a sample of Korean adults. PMID- 29786946 TI - Crowdfunding for prostate cancer and breast cancer. PMID- 29786947 TI - Does general experience affect self-assessment? AB - BACKGROUND: The assessment of clinical competence is critical in medical education. Understanding the effect of general experience on a physician's self assessment would help design more effective curricula and evaluations of procedural skills in postgraduate training and continuing professional development (CPD). In this observational study, we assessed the effect of general experience on the correlation between confidence and competence amongst experienced clinicians (ECs) and postgraduate trainees (PGTs) when learning an office-based procedure in pessary care. METHODS: We recruited 19 first-year family medicine residents and 18 family medicine faculty members in two outpatient academic clinics. All participants attended a simulation-based workshop for a routine gynaecological office procedure. We used a confidence survey as a measure of the participants' self-assessed competence and an objective structured clinical examination (OSCE) to evaluate participants' competence before and after the workshop. The assessment of clinical competence is critical in medical education RESULTS: We found no significant correlation between confidence and competence at baseline for either group (EC, r = 0.25, p = 0.35; PGT, r = 0.15, p = 0.60). After the workshop, we observed a statistically significant correlation between confidence and competence for ECs (r = 0.60, p = 0.01), but not for PGTs. The change in this correlation was not statistically significant for either group, however. DISCUSSION: Our findings suggest that ECs are not any more accurate in the assessment of their competence compared with PGTs. All procedural skills curricula can benefit from OSCE-format evaluation to better evaluate the improvement in performance of participants. PMID- 29786948 TI - Cocaine-induced pyoderma gangrenosum-like lesions. PMID- 29786949 TI - The qSOFA Score: A Simple and Accurate Predictor of Outcome in Patients with Glyphosate Herbicide Poisoning. AB - This study aimed to investigate whether the quick Sequential Organ Failure Assessment (qSOFA) score at emergency department (ED) presentation can help improve the risk assessment of glyphosate-surfactant herbicide (GlySH) poisoning complications. A total of 150 patients presenting with acute glyphosate herbicide ingestion were enrolled in this retrospective observational study. The qSOFA scores at presentation, DeltaqSOFA (calculated by subtracting the worst qSOFA score from 1 hr after admission from the qSOFA score at presentation), baseline characteristics, clinical courses and outcome were collected and analysed. A total of 41 patients had life-threatening complications (27.3%), and 14 patients died (9.3%). Patients with a qSOFA score of 0 at presentation had a 1.5% incidence rate of complications. As the qSOFA score at presentation increased from 1 to 3, the rate of life-threatening complications significantly increased from 29.6% to 100%. Patients with a DeltaqSOFA of 1 had a higher frequency of complications than did patients with a DeltaqSOFA of 0. The qSOFA score (OR: 8.39, 95% CI: 3.51-26.67) and DeltaqSOFA (OR: 27.60, 95% CI: 3.87-575.67) were associated with the development of life-threatening complications in the multivariate analysis. The qSOFA score showed high sensitivity (97.56%), and the DeltaqSOFA score showed high specificity (99.08%). The values of area under the curve were significantly higher in the models using the qSOFA and DeltaqSOFA than they were in the models using previously known prognostic factors (p < 0.01). The clinician should pay more attention to patients with high qSOFA scores at presentation or an increase in the qSOFA score 1 hr after admission. PMID- 29786950 TI - The double face of the same disease. PMID- 29786951 TI - Angiokeratoma corporis diffusum with normal enzyme activity: three new Italian cases. PMID- 29786952 TI - Arabidopsis small ubiquitin-related modifier protease ASP1 positively regulates abscisic acid signaling during early seedling development. AB - The small ubiquitin-related modifier (SUMO) modification plays an important role in the regulation of abscisic acid (ABA) signaling, but the function of the SUMO protease, in ABA signaling, remains largely unknown. Here, we show that the SUMO protease, ASP1 positively regulates ABA signaling. Mutations in ASP1 resulted in an ABA-insensitive phenotype, during early seedling development. Wild-type ASP1 successfully rescued, whereas an ASP1 mutant (C577S), defective in SUMO protease activity, failed to rescue, the ABA-insensitive phenotype of asp1-1. Expression of ABI5 and MYB30 target genes was attenuated in asp1-1 and our genetic analyses revealed that ASP1 may function upstream of ABI5 and MYB30. Interestingly, ASP1 accumulated upon ABA treatment, and ABA-induced accumulation of ABI5 (a positive regulator of ABA signaling) was abolished, whereas ABA-induced accumulation of MYB30 (a negative regulator of ABA signaling) was increased in asp1-1. These findings support the hypothesis that increased levels of ASP1, upon ABA treatment, tilt the balance between ABI5 and MYB30 towards ABI5-mediated ABA signaling. PMID- 29786953 TI - Iatrogenic Botulism Outbreak in Egypt due to a Counterfeit Botulinum Toxin A Preparation - A Descriptive Series of Patient Features and Outcome. AB - Iatrogenic botulism resulting from the substantial increase in use of botulinum neurotoxin type A (BoNT-A) treatment is rarely reported. We aimed to describe a large iatrogenic botulism outbreak in Egypt in June-July 2017. Nine patients developed botulism after receiving intramuscular injections of BoNT-A (dose: 200 300 IU) to treat cerebral palsy (N = 7), spastic dystonia (N = 1) and hyperhidrosis (N = 1). Detailed findings were available in five of nine cases. Patients were admitted to the hospital 5-10 days after the BoNT-A injection. Complaints included muscle weakness in the upper and lower limbs (N = 5), dysphagia (N = 5), dizziness (N = 2), dyspnoea (N = 2), dysphonia (N = 2), dysarthria (N = 2), fatigue (N = 1), diplopia (N = 1) and blurred vision (N = 1). Physical examination showed bilateral ptosis (N = 5), diminished gag reflex (N = 2), ophthalmoparesis (N = 1), facial paresis (N = 1) and tongue weakness (N = 1). Diagnosis was based on the patients' history and presentation and did not require any confirmatory test. On hospital admission, patients received supportive care and trivalent botulism type A/B/E antitoxin (250-500 IU) was started. No patient required mechanical ventilation. Immediate reversal of the most severe features was observed while varying degrees of peripheral muscular weakness persisted. Full recovery required 6-12 weeks. Cases were promptly reported to the Egyptian health authorities, and epidemiological investigations revealed that the outbreak was related to a recently imported highly concentrated unlicensed BoNT-A preparation sold as Neuroxin(r) . Immediate withdrawal from the market was ordered. In conclusion, iatrogenic botulism outbreak due to counterfeit botulism toxin may result in life-threatening features. The early administration of botulism antitoxin in addition to supportive care is life-saving. Clinicians should remain mindful of the risk of systemic botulism with BoNT-A therapy. PMID- 29786954 TI - Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients. AB - Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty-seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis-a-vis the group without fDGF (N = 22). In those with prolonged fDGF (>=21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF. PMID- 29786955 TI - Dual energy X-ray absorptiometry: gold standard for muscle mass? PMID- 29786956 TI - Rho Kinase and Protein Kinase C Pathways are Responsible for Enhanced Carbachol Contraction in Permeabilized Detrusor in a Rat Model of Cystitis. AB - Interstitial cystitis is a syndrome characterized by detrusor overactivity and chronic inflammation of the bladder. The mechanisms responsible for the altered smooth muscle contractility remain poorly understood. The aim of the study was to investigate the role of intracellular signalling pathways in carbachol-induced detrusor contraction in a rat model of interstitial cystitis. Cyclophosphamide (150 mg/kg, dissolved in saline) was injected to rats (Sprague-Dawley, female, 200-250 g) intraperitoneally once a day on days 1, 4 and 7 to induce interstitial cystitis. Control groups were injected with saline (0.9% NaCl). Detrusor smooth muscle strips were mounted in 1-ml organ baths containing HEPES-buffered modified Krebs' solution and permeabilized with 40 MUM beta-escin for 30 min. Carbachol induced contractions were significantly increased from 21.2 +/- 1.6% (saline treated) to 44 +/- 4.4% in cyclophosphamide-treated group. The Rho kinase inhibitor Y-27632 (8.8 +/- 2%) and the protein kinase C inhibitor GF-109203X (11.7 +/- 2.8%) inhibited the increased contractile response (44 +/- 4.4%) in rats with cystitis. The increased carbachol-induced contraction (44 +/- 4.4%) was also significantly inhibited by the sarcoplasmic reticulum ryanodine channel blocker ryanodine (25.8 +/- 3.2%) and the sarcoplasmic reticulum IP3 receptor blocker heparin (17.2 +/- 2.2%) in cystitis. RhoA protein levels in the bladder of cyclophosphamide-treated rats were significantly increased while pan-protein kinase C (alpha, beta and gamma isoforms) protein expression was unaltered between experimental groups. Carbachol-induced calcium sensitization at constant and clamped calcium (pCa 6) was also increased in cystitis (from 15.8 +/- 2.2% to 24.7 +/- 2.8%). This increased response (24.7 +/- 2.8%) was significantly inhibited by both Y-27632 (7.9 +/- 0.7%) and GF-109203X (4.4 +/- 1.5%). We conclude that interstitial cystitis is characterized by an enhanced carbachol contractile response as well as by calcium sensitization of the detrusor smooth muscle. Activation of Rho kinase and protein kinase C pathways may be the molecular culprits responsible for the augmented muscarinic response observed in cystitis. PMID- 29786957 TI - Statistical approaches to adjusting weights for dependent arms in network meta analysis. AB - Network meta-analysis compares multiple treatments in terms of their efficacy and harm by including evidence from randomized controlled trials. Most clinical trials use parallel design, where patients are randomly allocated to different treatments and receive only 1 treatment. However, some trials use within person designs such as split-body, split-mouth, and crossover designs, where each patient may receive more than one treatment. Data from treatment arms within these trials are no longer independent, so the correlations between dependent arms need to be accounted for within the statistical analyses. Ignoring these correlations may result in incorrect conclusions. The main objective of this study is to develop statistical approaches to adjusting weights for dependent arms within special design trials. In this study, we demonstrate the following 3 approaches: the data augmentation approach, the adjusting variance approach, and the reducing weight approach. These 3 methods could be perfectly applied in current statistical tools such as R and STATA. An example of periodontal regeneration was used to demonstrate how these approaches could be undertaken and implemented within statistical software packages and to compare results from different approaches. The adjusting variance approach can be implemented within the network package in STATA, while reducing weight approach requires computer software programming to set up the within-study variance-covariance matrix. PMID- 29786958 TI - Variability in student perceptions of mistreatment. AB - BACKGROUND: As medical schools strive to improve the learning environment, it is important to understand medical students' perceptions of mistreatment. The purpose of this study was to explore student interpretations of previously reported mistreatment incidents to better understand how they conceptualise the interactions. METHODS: Medical students were presented with case scenarios of previously reported instances of mistreatment and asked to indicate their agreement as to whether the scenarios demonstrated mistreatment, using a five point Likert scale (1, strongly disagree; 5, strongly agree). It is important to understand medical student's perceptions of mistreatment RESULTS: One hundred and twenty-seven third-year medical students gave feedback on 21 mistreatment cases. There was variability in the categorisation of the scenarios as mistreatment. The highest degree of consensus (96% agreement) was for a scenario in which a resident claimed a student made statements about a patient's status that the student did not make. There was also relative consensus on three additional scenarios: (1) a patient making disparaging remarks about a student's role in health care in relation to the student's ethnicity (88% agreement); (2) a resident asking a student to run personal errands (86% agreement); and (3) a nurse calling a student an expletive in front of others (77% agreement). For the majority of the cases, there was no consensus amongst students as to whether mistreatment had occurred. Students self-identifying as minorities and students who had previously reported mistreatment were more likely to perceive mistreatment in the scenarios. CONCLUSIONS: There is remarkable variability, and in many cases a lack of agreement, in medical student perceptions of mistreatment. This inconsistency needs to be considered in order to effectively address and mitigate the issue. PMID- 29786959 TI - Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects. AB - Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of adults with type 2 diabetes mellitus, is expected to be coadministered with sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open label, randomized, single-dose, crossover studies were conducted in healthy adults to assess the potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 mg (n = 12), metformin 1000 mg (n = 18), glimepiride 1 mg (n = 18), or simvastatin 40 mg (n = 18). Noncompartmental pharmacokinetic parameters derived from plasma concentration-time data were analyzed using mixed effects models to assess interactions. Coadministration of sitagliptin, metformin, glimepiride, or simvastatin with ertugliflozin had no effect on area under the plasma concentration-time profile from time 0 to infinity (AUCinf ) or maximum observed plasma concentration (Cmax ) of ertugliflozin (per standard bioequivalence boundaries, 80% to 125%). Similarly, ertugliflozin did not have any impact on AUCinf or Cmax of sitagliptin, metformin, or glimepiride. AUCinf for simvastatin (24%) and simvastatin acid (30%) increased slightly after coadministration with ertugliflozin and was not considered clinically relevant. All treatments were well tolerated. The lack of clinically meaningful pharmacokinetic interactions demonstrates that ertugliflozin can be coadministered safely with sitagliptin, metformin, glimepiride, or simvastatin without any need for dose adjustment. PMID- 29786960 TI - Atomic-Resolution Structure of a Class C beta-Lactamase and Its Complex with Avibactam. AB - beta-Lactamases (BLs) are important antibiotic-resistance determinants that significantly compromise the efficacy of valuable beta-lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non-beta-lactam BL inhibitor introduced into clinical practice. Ceftazidime avibactam represents one of the few last-resort antibiotics available for the treatment of infections caused by near-pandrug-resistant bacteria. TRU-1 is a chromosomally encoded AmpC-type BL of Aeromonas enteropelogenes, related to the FOX-type BLs and constitutes a good model for class C BLs. TRU-1 crystals provided ultrahigh-resolution diffraction data for the native enzyme and for its complex with avibactam. A comparison of the native and avibactam-bound structures revealed new details in the conformations of residues relevant for substrate and/or inhibitor binding. Furthermore, a comparison of the TRU-1 and Pseudomonas aeruginosa AmpC avibactam-bound structures revealed two inhibitor conformations that were likely to correspond to two different states occurring during inhibitor carbamylation/recyclization. PMID- 29786962 TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 21/2018. PMID- 29786961 TI - Corrigendum: The Structural Fate of Individual Multicomponent Metal-Oxide Nanoparticles in Polymer Nanoreactors. PMID- 29786963 TI - Design and Fabrication of Printed Paper-Based Hybrid Micro-Supercapacitor by using Graphene and Redox-Active Electrolyte. AB - Inspired by future needs of flexible, simple, and low-cost energy storage devices, smart graphene-based micro-supercapacitors on conventional Xerox paper substrates were developed. The use of redox-active species (iodine redox couple) was explored to further improve the paper device's performance. The device based on printed graphene paper itself already had a remarkable maximum volumetric capacitance of 29.6 mF cm-3 (volume of whole device) at 6.5 mA cm-3 . The performance of the hybrid electrode with redox-active potassium iodide at the graphene surface was tested. Remarkably, the hybrid device showed improved volumetric capacitance of 130 mF cm-3 . The maximum energy density for a graphene+KI device in H2 SO4 electrolyte was estimated to be 0.026 mWh cm-3 . Thus, this work offers a new simple, and lightweight micro-supercapacitor based on low-cost printed graphene paper, which will have great applications in portable electronics. PMID- 29786964 TI - A Thorough QT/QTc Study With Laquinimod, a Novel Immunomodulator in Development for Multiple Sclerosis and Huntington Disease. AB - In this randomized double-blind study, 4 groups of healthy subjects (50 per arm) participated to evaluate the effect of laquinimod, an oral treatment in development for multiple sclerosis and Huntington disease, on the QTc interval. Subjects received a dose of either 0.6 or 1.2 mg/day laquinimod for 14 days, placebo for 14 days, or 13 days of placebo followed by a dose of 400 mg moxifloxacin on day 14. Continuous 12-lead electrocardiograms were recorded on day -1 (baseline) and days 14 to 17, and quadruplicate electrocardiograms were extracted at predefined time points. The primary measure was time-matched change from baseline in individual QTc (QTcI), and an analysis of variance was conducted on the placebo-corrected change from baseline data (ddQTcI). Pharmacokinetic pharmacodynamic and safety assessments were included. Results showed that the upper limits of the 2-sided 90%CI for ddQTcI for both laquinimod doses were below 10 millisconds at all time points, whereas lower limits for moxifloxacin were above 5 milliseconds. No notable changes in ECG parameters were observed. Pharmacokinetic/pharmacodynamic analysis showed no positive correlation between laquinimod plasma levels and QTcI. In conclusion, laquinimod was not found to affect cardiac repolarization or to cause prolongation of QTcI at doses of 0.6 and 1.2 mg/day. PMID- 29786965 TI - L- and D-threo ethylphenidate concentrations, pharmacokinetics, and pharmacodynamics in horses. AB - Ethylphenidate is a psychostimulant and analog of the commonly prescribed compound, methylphenidate (Ritalin(r)). There are a limited number of studies describing the disposition and pharmacologic/toxicological effects of ethylphenidate in any species. The abuse potential in equine athletes along with the limited data available regarding administration in horses necessitates further study. The objectives of the current study were to describe drug concentrations, develop an analytical method that could be used to regulate its use, and describe the pharmacodynamic effects of ethylphenidate in horses. To that end, 12 horses were randomized into 3 dose groups (intravenous: 10 mg or 40 mg, oral: 40 mg). Ethylphenidate was administered and blood and urine samples were collected prior to and for up to 72 hours post drug administration. Concentrations of D-threo ethylphenidate and the metabolite ritalinic acid were measured using Liquid Chromatography-tandem Mass Spectrometry. L-threo ethylphenidate concentrations were estimated from D-threo ethylphenidate concentrations. Serum concentrations of ethylphenidate were below detectable levels by 8, 18, and 12 hours following intravenous administration of 10 mg and 40 mg and oral administration of 40 mg, respectively. Ritalinic acid was non detectable at 72 hours in the group that received a 10-mg intravenous and 40-mg oral dose of ethylphenidate. Ritalinic acid concentrations were below the LOQ at 72 hours following intravenous administration of 40 mg of ethylphenidate. While the number of animals per dose group were small, no stimulatory behavior or significant changes in heart rate were noted. Untoward effects including gastrointestinal adverse effects were noted in all dose groups. PMID- 29786966 TI - Controlled Selectivity of CO2 Reduction on Copper by Pulsing the Electrochemical Potential. AB - We demonstrate a simple strategy to enhance the CO2 reduction reaction (CO2 RR) selectivity by applying a pulsed electrochemical potential to a polycrystalline copper electrode. By controlling the pulse duration, we show that the hydrogen evolution reaction (HER) is highly suppressed to a fraction of the original value (<5 % faradaic efficiency) and selectivity for the CO2 RR dramatically improves (>75 % CH4 and >50 % CO faradaic efficiency). We attribute the improved CO2 RR selectivity to a dynamically rearranging surface coverage of hydrogen and intermediate species during the pulsing. Our finding provides new insights into the interplay of transport and reaction processes as well as timescales of competing pathways to enable new opportunities to tune CO2 RR selectivity by adjusting the pulse profile. Additionally, the pulsed potential method we describe can be easily applied to other catalysts materials to improve their CO2 RR selectivity. PMID- 29786968 TI - p62-mediated autophagy affects nutrition-dependent insulin receptor substrate 1 dynamics in 3T3-L1 preadipocytes. AB - AIMS/INTRODUCTION: Previous studies have shown that an organism's nutritional status changes the protein levels of insulin receptor substrate 1 (IRS-1) in a tissue-specific manner. Although the mechanisms underlying the regulation of IRS 1 in the nutrient-rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient-poor conditions remain unknown. The aim of the present study was to investigate how IRS-1 protein levels change depending on the nutritional status of 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3T3-L1 preadipocytes were treated with glucose-, amino acid- and serum free medium for starvation. IRS-1 protein levels were detected by western blot. Autophagy activity was observed by western blot and fluorescence microscopy. The effect of autophagy and p62, an adaptor for selective autophagy, on IRS-1 protein levels under starvation conditions was examined by western blot and immunocytochemistry. RESULTS: We showed that the levels of IRS-1, but not those of insulin receptor and protein kinase B, decreased when starvation activated autophagy. The inhibition of autophagy by chloroquine or autophagy-related 7 (Atg7) ribonucleic acid interference counteracted the starvation-induced decrease of IRS-1. Additionally, Atg7 knockdown increased insulin-stimulated phosphorylation of protein kinase B under starvation conditions. Furthermore, p62 colocalized with IRS-1 under starvation conditions, and p62 knockdown counteracted the starvation-induced degradation of IRS-1. CONCLUSIONS: Autophagy through p62 plays an important role in regulating IRS-1 protein levels in response to nutritional deficiency. The present findings suggest that autophagy might function as energy depletion-sensing machinery that finely tunes insulin signal transduction. PMID- 29786967 TI - Developmental Chromatin Restriction of Pro-Growth Gene Networks Acts as an Epigenetic Barrier to Axon Regeneration in Cortical Neurons. AB - Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility. When applied to the developing cortex, this pipeline detected overall closure of chromatin in sub-networks of genes associated with axon growth. We next analyzed mature CNS neurons that were supplied with various pro regenerative transcription factors. Unlike prior results with SOX11 and KLF7, here we found that neither JUN nor an activated form of STAT3 promoted substantial corticospinal tract regeneration. Correspondingly, chromatin accessibility in JUN or STAT3 target genes was substantially lower than in predicted targets of SOX11 and KLF7. Finally, we used the pipeline to predict pioneer factors that could potentially relieve chromatin constraints at growth associated loci. Overall this integrated analysis substantiates the hypothesis that dynamic chromatin accessibility contributes to the developmental decline in axon growth ability and influences the efficacy of pro-regenerative interventions in the adult, while also pointing toward selected pioneer factors as high priority candidates for future combinatorial experiments. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol 00: 000-000, 2018. PMID- 29786970 TI - Density Functional Theory Calculations Revealing Metal-like Band Structures for Ultrathin Germanium (111) and (211) Surface Layers. AB - To find out if germanium possesses facet-dependent electrical-conductivity properties, surface-state density functional theory (DFT) calculations were performed on one to six layers of germanium (100), (110), (111), and (211) planes. Tunable Ge(100) and Ge(110) planes always present the same semiconducting band structure with a band gap of 0.67 eV expected of bulk germanium. In contrast, one, two, four, and five layers of Ge(111) and Ge(211) plane models show metal-like band structures with continuous density of states (DOS) throughout the entire band. For three and six layers of Ge(111) and Ge(211) plane models, the normal semiconducting band structure was obtained. The plane layers with metal-like band structures also show Ge-Ge bond-length deviations and bond distortions, as well as significantly different 4s and 4p frontier-orbital electron counts and relative percentages integrated over the valence and conduction bands from those of the semiconducting state. These differences should contribute to strikingly dissimilar band structures. The calculation results suggest the observation of facet-dependent electrical-conductivity properties of germanium materials; when making transistors from germanium, the facet effects with shrinking dimensions approaching 3 nm may also need to be considered. PMID- 29786971 TI - Intergenerational teen pregnancy: a population-based cohort study. AB - OBJECTIVE: To estimate the intergenerational association in teenage pregnancy, and whether there is a coupling tendency between a mother and daughter in how their teen pregnancies end, such as a termination of pregnancy (TOP) versus a live birth. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. POPULATION: A total of 15 097 mothers and their 16 177 daughters. METHODS: Generalised estimating equations generated adjusted odds ratios (aOR) of a daughter experiencing a teen pregnancy in relation to the number of teen pregnancies her mother had. Multinomial logistic regression estimated the odds that a teen pregnancy ended with TOP among both mother and daughter. All models were adjusted for maternal age and world region of origin, the daughter's socio demographic characteristics and comorbidities, mother-daughter cohabitation, and neighbourhood-level teen pregnancy rate. MAIN OUTCOME MEASURES: Teen pregnancy in the daughter, between ages 15 and 19 years, and also the nature of the daughter's teen pregnancy, categorised as (1) no teen pregnancy, (2) at least one teen pregnancy, all exclusively ending with a live birth, and (3) at least one teen pregnancy, with at least one teen pregnancy ending with a TOP. RESULTS: The proportion of daughters having a teen pregnancy among those whose mother had zero, one, two, or at least three teen pregnancies was 16.3, 24.9, 33.5 and 36.3%, respectively. The aOR of a daughter having a teen pregnancy was 1.42 (95% CI 1.25-1.61) if her mother had one, 1.97 (95% CI 1.71-2.26) if she had two, and 2.17 (95% CI 1.84-2.56) if her mother had three or more teen pregnancies, relative to none. If a mother had at least one teen pregnancy ending with TOP, then her daughter had an aOR of 2.12 (95% CI 1.76-2.56) for having a teen pregnancy also ending with TOP; whereas, if a mother had at least one teen pregnancy, all ending with a live birth, then her daughter had an aOR of 1.73 (95% CI 1.46-2.05) for that same outcome. CONCLUSION: There is a strong intergenerational occurrence of teenage pregnancy between a mother and daughter, including a coupling tendency in how the pregnancy ends. TWEETABLE ABSTRACT: Strong intergenerational association for teenage pregnancy between mother and daughter. PMID- 29786969 TI - Hippocampal lipidome and transcriptome profile alterations triggered by acute exposure of mice to GSM 1800 MHz mobile phone radiation: An exploratory study. AB - BACKGROUND: The widespread use of wireless devices during the last decades is raising concerns about adverse health effects of the radiofrequency electromagnetic radiation (RF-EMR) emitted from these devices. Recent research is focusing on unraveling the underlying mechanisms of RF-EMR and potential cellular targets. The "omics" high-throughput approaches are powerful tools to investigate the global effects of RF-EMR on cellular physiology. METHODS: In this work, C57BL/6 adult male mice were whole-body exposed (nExp = 8) for 2 hr to GSM 1800 MHz mobile phone radiation at an average electric field intensity range of 4.3 17.5 V/m or sham-exposed (nSE = 8), and the RF-EMR effects on the hippocampal lipidome and transcriptome profiles were assessed 6 hr later. RESULTS: The data analysis of the phospholipid fatty acid residues revealed that the levels of four fatty acids [16:0, 16:1 (6c + 7c), 18:1 9c, eicosapentaenoic acid omega-3 (EPA, 20:5 omega3)] and the two fatty acid sums of saturated and monounsaturated fatty acids (SFA and MUFA) were significantly altered (p < 0.05) in the exposed group. The observed changes indicate a membrane remodeling response of the tissue phospholipids after nonionizing radiation exposure, reducing SFA and EPA, while increasing MUFA residues. The microarray data analysis demonstrated that the expression of 178 genes changed significantly (p < 0.05) between the two groups, revealing an impact on genes involved in critical biological processes, such as cell cycle, DNA replication and repair, cell death, cell signaling, nervous system development and function, immune system response, lipid metabolism, and carcinogenesis. CONCLUSIONS: This study provides preliminary evidence that mobile phone radiation induces hippocampal lipidome and transcriptome changes that may explain the brain proteome changes and memory deficits previously shown by our group. PMID- 29786972 TI - Two-Step Synthesis of Cobalt Iron Alloy Nanoparticles Embedded in Nitrogen-Doped Carbon Nanosheets/Carbon Nanotubes for the Oxygen Evolution Reaction. AB - There is a vital need to explore highly efficient and stable non-precious-metal catalysts for the oxygen evolution reaction (OER) to reduce the overpotential and further improve the energy-conversion efficiency. Herein, we report a unique and cost-effective lyophilization and thermal treatment two-step procedure to synthesize a high-performance hybrid consisting of CoFe alloy nanoparticles embedded in N-doped carbon nanosheets interspersed with carbon nanotubes (CoFe-N CN/CNTs) hybrid. The lyophilization step during the catalyst preparation leads to a uniform dispersion of carbon-like precursors and avoids the agglomeration of metal particles. In addition, the inserted CNTs and doped N in this hybrid provide a good electrical conductivity, an abundance of chemically active sites, good mass transport capability, and effective gas adsorption/release channels. All these lead to a high specific surface area of 240.67 m2 g-1 , favorable stability, and remarkable OER activities with an overpotential of only 285 mV at a current density of 10 mA cm-2 and a Tafel slope of 51.09 mV dec-1 in 1.0 m KOH electrolyte, which is even superior to commercial IrO2 catalysts. The CoFe-N CN/CNTs hybrid thus exhibits great potential as a highly efficient and earth abundant anode OER electrocatalyst. PMID- 29786973 TI - Amniotic fluid lactic acid and matrix metalloproteinase-8 levels at the time of fetal surgery for a spine defect: association with subsequent preterm prelabour rupture of membranes. AB - OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP 9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes. PMID- 29786974 TI - Embryonic exposure to environmentally relevant concentrations of a brominated flame retardant reduces the size of song-control nuclei in a songbird. AB - Environmental contaminants have the potential to act as developmental stressors and impair development of song and the brain of songbirds, but they have been largely unstudied in this context. 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is a brominated flame retardant congener that has demonstrated endocrine disrupting effects, and has pervaded the global environment. We assessed the effects of in ovo exposure to environmentally relevant levels of BDE-99 on the neuroanatomy of the song-control system in a model songbird species, the zebra finch (Taeniopygia guttata). Embryos were exposed via egg injection to a vehicle control (DMSO), 10, 100, or 1000 ng BDE-99/g egg on the day the egg was laid. Chicks were raised to sexual maturity to investigate long-term effects of BDE-99 on the adult male brain. Three key song-control nuclei (Area X, HVC, RA) all showed a dose-dependent trend toward decreasing volume as BDE-99 concentration increased, and birds exposed to 1000 ng/g in ovo BDE-99 had significantly smaller song-control nuclei volume compared to control birds. High environmental concentrations of BDE-99 in avian tissues can be within that range and thus could affect development of the song-control system in birds, and potentially other processes. We previously found that BDE-99 exposure during the nestling period had no effect of on the song-control system, although it did have significant effects on some behaviural endpoints. Taken together, these results suggest that exposure to polybrominated diphenyl ether (PBDEs) during critical developmental windows can significantly alter neurological development. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. PMID- 29786975 TI - A comparison of one-stage vs two-stage individual patient data meta-analysis methods: A simulation study. AB - BACKGROUND: Individual patient data (IPD) meta-analysis allows for the exploration of heterogeneity and can identify subgroups that most benefit from an intervention (or exposure), much more successfully than meta-analysis of aggregate data. One-stage or two-stage IPD meta-analysis is possible, with the former using mixed-effects regression models and the latter obtaining study estimates through simpler regression models before aggregating using standard meta-analysis methodology. However, a comprehensive comparison of the two methods, in practice, is lacking. METHODS: We generated 1000 datasets for each of many simulation scenarios covering different IPD sizes and different between study variance (heterogeneity) assumptions at various levels (intercept and exposure). Numerous simulation settings of different assumptions were also used, while we evaluated performance both on main effects and interaction effects. Performance was assessed on mean bias, mean error, coverage, and power. RESULTS: Fully specified one-stage models (random study intercept or fixed study-specific intercept; random exposure effect; and fixed study-specific effects for covariate) were the best performers overall, especially when investigating interactions. For main effects, performance was almost identical across models unless intercept heterogeneity was present, in which case the fully specified one stage and the two-stage models performed better. For interaction effects, differences across models were greater with the two-stage model consistently outperformed by the two fully specified one-stage models. CONCLUSIONS: A fully specified one-stage model should be preferred (accounting for potential exposure, intercept, and, possibly, interaction heterogeneity), especially when investigating interactions. If non-convergence is encountered with a random study intercept, the fixed study-specific intercept one-stage model should be used instead. PMID- 29786976 TI - Multiple acquired pigmented lesions in a patient affected by melanoma. PMID- 29786977 TI - Impact of shift work on critical care nurses. AB - Shift work is a common practice in the health care field to maintain 24-hour patient care. The purpose of this article is to recognize the negative impact of shift work on critical care nurses, and identify strategies to mitigate these effects. A review of the literature was completed, using the search terms: 'shift work, 'critical care', impact, and health. The literature revealed that shift work has an adverse effect on the health of a nurse. Some of the health implications include stress, sleep deprivation, cardiovascular disease, gastrointestinal symptoms, and mental health illnesses. Furthermore, shift work impacts a nurse's social life and may result in patient harm. Strategies to reduce the negative impact of shift work will be focused on educating critical care nurses and managers. These strategies include frontline staff maintaining a moderate amount of exercise, sustaining a well-balanced diet, using relaxation techniques, reducing the use of cigarettes, working an eight-hour work day, and napping during scheduled breaks. Recommendations for managers include implementing quiet time at the workplace, providing a safe space for staff to nap during breaks, facilitating an eight-hour work day, and encouraging a multidisciplinary team approach when managing workload. PMID- 29786978 TI - Informal debriefing: Underutilization in critical care settings. AB - Debriefing is the active reflection, conceptualization and basis for reinforced or changed behaviour in response to new learning experiences. It has been acknowledged as a valuable tool towards achieving learning outcomes informal teaching or training ven- ues. However, there is limited recognition of the importance of informal debriefing in the clinical setting, especially in critical care settings. Additional specialized training is received by registered nurses to be able to care for clinically unstable patients in critical care units. Informal debriefing can allow critical care nurses to learn from the experience of exposure to different clinical situations and progress towards becoming competent, expert clinicians. The purpose of this article is to present a discussion highlighting informal debriefing and the importance of providing feedback to novice and experienced nurses in critical care areas. The underutilization of informal debriefing will be explored together with possible barriers and challenges to its use. Solutions to overcoming such barriers will be proposed, as a means of ensuring that valuable reflection and learning opportunities are not lost. These suggestions will emphasize the importance of how informal debriefing promotes professional and personal development, and safer patient care. PMID- 29786980 TI - Should We Aim For Cured, Doing Better or Still Working On It? PMID- 29786979 TI - Moral distress and burnout among cardiovascular surgery intensive care unit healthcare professionals: A prospective cross-sectional survey. AB - BACKGROUND: The intensive care unit (IGU) is a busy, high stress, complex environment in which health care professionals routinely provide numerous forms of advanced life support and life sustaining measures to a wide mix of critically ill patients. Frontline ICU professionals directly involved in patient care may be subjected to considerable psychosocial stressors and be susceptible to moral distress and burnout. PURPOSE: To describe and compare the prevalence and contributing factors to moral distress and burnout among ICUprofessionals in a large quaternary cardiovascular surgery ICU (CVICU). METHODS: Web-based survey of ICU professionals (registered nurses [RN]/nurse practitioners [NP]; registered respiratory therapists [RRT]; allied health [AH] and physicians [MD]) working in a 24-bed CVICU at the Mazankowski Alberta Heart Institute, between June 15-29, 2015. The survey captured sociodemographic data and integrated the Moral Distress Scale-Revised, the Maslach Burnout Inventory', and a validated job satisfaction questionnaire. FINDINGS: One hundred sixty-nine providers completed the sur- vey (response rate 88%). The majority of respondents were aged 26-34 years old (45%), female (79%), married or common law (50%), full-time employed (78%) and had been working in the CVICU for >5 years (46%). Moral distress scores were highest among RN/NP (med [IQR] 80 [57-110]) and RRT (85 [61-104]) compared to AH (54 [39-66]) and physicians (66 [43-82], p=0.05). The highest-ranked sources of moral distress were related to controversies on end-of-life care ("Continue to participate in the care for a hopelessly ill person who is being sustained on a ventilator, when no one will make a decision to withdrawal support") and poor communication ("witness healthcare providers giving false hope' to a patient or family"). High, moderate and low levels of burnout syndrome were found in 64.0%, 22.7% and 13.3% of respondents with significantly greater levels among non-physician professionals (p<0.001). Job satisfaction was highest for physicians compared with other professionals (p<0.001). The item "the recognition you get for good work" was consistently rated as poor across all groups. Moral distress and burnout scores were positively correlated (p<0. 001), whereas both were neg- atively correlated with job satisfaction (p<0.001 for both). This was primarily driven by RN/NP scores. CONCLUSION: Moral distress and burnout are common in health- care professionals in a large academic cardiovascular surgery ICU, in particular among nurses and respiratory therapists. Both moral distress and burnout have a negative perception on job satisfaction. These findings will direct strategies to mitigate moral distress and burnout along with enhancing patient care and improving the workplace environment. PMID- 29786981 TI - How You Can Address the Health Effects of Childhood Poverty. PMID- 29786982 TI - 8 Ways to Be A Good Sober Home Neighbor. PMID- 29786983 TI - How Behavioral Health Can Benefit From Population Health Strategies. PMID- 29786984 TI - Navigate the Naloxone Economy. PMID- 29786985 TI - Medication Non-Adherence Sends Healthcare Costs Soaring. PMID- 29786986 TI - Election 2016: Where the Candidates Stand. PMID- 29786987 TI - 5 Factors Influencing Telemental Health. PMID- 29786988 TI - Alleviative effect of some phytochemicals on cyadox-induced oxidative damage in rabbit erythrocytes. AB - This study was carried out to evaluate the effects of different concentrations of cyadox (CYA), cinnamaldehyde (CIN) and resveratrol (RES) on rabbit isolated erythrocytes in two experiments. Experiment 1 evaluated the effects of different concentrations (2.5, 5, 10, 20, 40, 60, 80 and 100) MUg/mI of CYA and pM of both CIN and RES separately on isolated erythrocytes in order to make the concentration response curve. Results indicated that CYA caused a significant depletion of reduced glutathione (GSH) content compared to control at 40 MUg/ml and the depletion increased by increasing the concentration. On the other hand, both RES and CIN showed a highly significant elevation of GSH content at 40 MUM being more effective by increasing concentrations. Experiment 2 investigated the potential benefits of using CIN and RES separately or in combination on CYA induced alterations in isolated rabbit erythrocytes (the used concentrations were based on the results of experiment 1). Results revealed that exposure to CYA caused a significant decrease in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) and total protein (TP) contents, CYA also elevated extracellular hemoglobin (Hb) and adenosine triphosphate (ATP), increased the malonaldehyde (MDA) and protein carbonyl (PrC) contents with increasing caspase3 and caspase8 activities suggesting CYA pro-oxidant effect. Both CIN and RES were able to inverse these hazardous effects of CYA. However, CIN was more effective than RES, and their combination showed a positive synergistic effect in protecting cells against oxidative injury caused by CYA. PMID- 29786989 TI - Gallus gallus coxsackievirus and adenovirus receptor facilitates the binding of fowl adenovirus serotype 1 in chickens. AB - Coxsackievirus and adenovirus receptor (UXADR) is an integral membrane protein that serves as a receptor for coxsackie B viruses and adenovirus types 2 and 5. Previous studies demonstrated that Fowl adenovirus (FAV) can also utilize Homo sapiens CXADR to infect cells. FAV is a double-stranded DNA virus of the family Adenoviridae. FAV causes inclusion body hepatitis and hydropericardium syndrome in chickens. In addition, FAV serotypes 1 and 8 have recently been shown to cause gizzard erosion in chickens. These chicken diseases and growth insufficiency caused by FAV infection result in great economic loss. Thus, identifying and characterizing the viral receptor would further enhance our understanding of the mechanisms underlying virus infection and histocompatibility. Here, in order to determine the FAV receptor in chickens, we investigated the effect of the recently identified Gallus gallus CXADR (ggCXADR) on FAV infection. Overexpression of ggCXADR in CHO cells resulted in increased FAV binding and expression of early FAV genes. However, the propagation of infectious viruses in CHO cells expressing ggCXADR was not detected. These findings provide the basis for further studies aimed at elucidating the infection mechanism of FAV. Further research is required to characterize the additional host factors involved in FAV infection and life cycle. PMID- 29786990 TI - Methylprednisolone sodium succinate reduces spinal cord swelling but does not affect recovery of dogs with surgically treated thoracolumbar intervertebral disk herniation. AB - The effect of methylprednisolone sodium succinate (MPSS) therapy was studied in 50 dogs with surgically treated Hansen type I thoracolumbar intervertebral disk herniation (TL-IVDH). Administration of MPSS significantly reduced the swelling of the spinal cord. The sensitivity of localization of disk extrusion using myelography in the MPSS group was 92.3%, and in the non-administration group was 83.3%. No significant difference in recovery rate or length of recovery time was found between the two groups. Administration of MPSS reduced spinal cord swelling, but has no effect on recovery in dogs after surgery for TL-IVDH. PMID- 29786991 TI - The effects of administering lactic acid bacteria sealed in a capsule on the intestinal bacterial flora of cattle. AB - We examined the effects of encapsulated lactic acid bacteria administrated orally to lactating cattle on the intestinal flora. A dose of 3 X 1011 colony forming unit (cfu) of freeze-dried Lactobacillus coryniformis subsp. torquens (JCM1099) encapsulated in an enteric capsule capable of bypassing the rumen was administered for seven days. DNA was extracted from feces 0 and 24 hr after daily administration. Metagenomic analysis showed an increasing trend of the alpha diversity, an index of the species diversity. Furthermore, principal component analysis of intestinal flora revealed that cattle could be differentiated by JCM1099 capsule and suspension administration via principal components 1, 2, and 3. We conclude that administration of encapsulated JCM1099 can alter the intestinal bacterial flora of cattle. PMID- 29786992 TI - Molecular study of feline hemoplasmas in free- ranging fishing cats (Prionailurus viverrinus) in Thailand. AB - Feline hemoplasmas, consisting of Mycoplasma haemofelis (M. haemofelis), Candidatus Mycoplasma haemominutum (Ca. M. haemominutum), and Candidatus Mycoplasma turicensis (Ca. M. turicensis), cause feline infectious anemia and zoonoses. Using multiplex PCR and phylogenetic analysis based on 16S rRNA, 22 blood samples from fishing cats (Prionailurus viverrinus) living in Khao Sam Roi Yot National Park, Thailand were determined positive for M. haemofelis (13.6%)and Ca. M. haemominutum (22.7%). M. haemofelis and Ca. M. haemominutum infection can result severe anemia and asymptomatic, respectively. However, not all positive cases exhibit anemia symptoms. Future study of hemoplasma infection in wild felids is necessary for conservation and the preservation of public health in Thailand. PMID- 29786993 TI - Genetic diversity of Thoroughbred horse population from Bosnia and Herzegovina based on 17 microsatellite markers. AB - The focus of this study was on genetic diversity of TB horse population raised in B&H. Genomic DNA was genotyped by using 17 microsatellite markers. A total of 103 alleles were detected. The average number of alleles per locus was 6.059 and effective number of alleles was 3.293. Means of observed and expected heterozygosity were calculated 0.645 and 0.696, respectively. The average PIC values was 0.649 and inbreeding coefficient was 0.090. Based on all observed parameters, ASB2 locus showed the highest genetic diversity while locus HMS2 was the least diverse. These results suggest that the population of TB horses from B&H is not affected by substantial loss of genetic diversity, indicating the presence of reasonably high level of genetic variability. PMID- 29786994 TI - The role of microRNAs in endometrial cancer and influence on future therapy: focusing on miRNA-21. AB - MicroRNAs are small noncoding polynucleotides, which are involved in numerous biological processes including cell proliferation, differentiation, embryonic development, as well as regulation of cell death and survival. Recent investigations have shown impact of microRNAs on cancers prognosis and diagnosis. Current review focused on the role of microRNA-21 in cancers tumorigenesis. Endometrial cancer is the most common gynecological malignancy and the fourth most common in general classification of cancers in Western Europe; thus discovering new molecules may become a useful diagnostic tool. Furthermore, in this review, the authors emphasized microRNAs having considerable influence on endometrial cancer development. Finally, they highlighted the role of microRNAs as a target for future therapy and circulating microRNAs as a potential biomarker in malignancies. PMID- 29786995 TI - The significance of the pluripotency and cancer stem cell-related marker NANOG in diagnosis and treatment of ovarian carcinoma. AB - Ovarian cancer is among the most common gynecologic cancers and unfortunately the most common cause of death from gynecologic malignancies. Due to few early symptoms and insufficient screening programs, an early diagnosis of ovarian cancer is very difficult and new biomarkers related to early ovarian carcinogenesis are needed. In the last years a growing scientific knowledge about cancer stem cells and their markers opened a new perspective on screening and early diagnosis of ovarian cancer. The transcription factor NANOG is not only a pluripotency and cancer stem cell-related marker, but also promotes cancer stem cell-like characteristics of tumor, tumor growth, dissemination, immune evasion, and resistance to conventional therapy. The recent data showed that small stem cells resembling very small embryonic-like stem cells are present in the ovarian surface epithelium of adult human ovaries. These cells expressed several genes related to primordial germ cells, germinal lineage, and pluripotency, including NANOG, therefore their involvement in the manifestation of ovarian cancer are not excluded. As majority of cancer cells within a tumor are non tumorigenic, the therapies targeting these cells cause tumor regression, but the survived cancer stem cells regenerate the tumor, so tumor relapse or reoccur. The eradication of cancer actually requires the elimination of cancer stem cells, therefore new strategies in treatment that specifically target cancer stem cells are urgently needed. Although the therapeutic efficacy of targeting NANOG as a cancer treatment method is still in experimental phase, the gene therapy with small interfering RNA or short hairpin RNA have already shown some promising therapeutic potential. The authors can conclude that NANOG represents a promising diagnostic marker and agent for target therapy of ovarian cancer. PMID- 29786997 TI - Is human epididymis protein 4 an effective tool for the differential diagnosis of benign and malignant endometrial tumours? AB - PURPOSE OF INVESTIGATION: This study was designed to evaluate the use of human epididymis protein 4 (HE4) as a biomarker in the differential diagnosis of malignant and benign endometrial tumours. MATERIALS AND METHODS: The study, conducted between July 2009 and June 2014, included a total of 150 patients with endometrioid adenocarcinoma and a control group of 150 patients with benign endometrial lesions. The serum of all patients was analyzed with respect to HE4 and CA125 levels. The median and ranges of serum levels were determined in relation to histological results. The statistical analysis procedure employed in this study utilized logarithmic-transformed values of biomarkers and logistic regression. RESULTS: An analysis of two groups of patients with different histologies yielded a statistically significant difference (p-value < 0.05) only in the case of HE4, in which case a cut-off value of 48.5 pmol/l resulted in an achieved sensitivity of 87.8%, a specificity of 56.6%, and a negative predictive value of 81.1%. CONCLUSION: In combination with clinical and ultrasound findings, HE4 could help with the differentiation of prognostically varied patient groups as well as with the decision-making process associated with the development of individual treatment plans. However, the optimal cut-off for HE4 has not been established yet and further studies are needed. PMID- 29786996 TI - Trocar metastases in laparoscopic approach for gynecologic malignancies. A short review of the literature. AB - INTRODUCTION: Compared to laparotomy, laparoscopy has many benefits for patients, such as shorter recovery and lower morbidity rates. Port site metastases after laparoscopic approach in the treatment of gynecologic malignancies are uncommon. The purpose of this review is to identify and summarize possible risk factors for port-site metastases in patients undergoing laparoscopic surgery in the ambit of gynecologic oncology. DISCUSSION: The precise incidence of port-site metastases is not well known because many patients are not followed-up during the whole postoperative period. Possible risk factors that can increase the risk of port site metastases can be the presence of large masses in the abdomen, especially in the presence of concomitant ascites and in patients treated for ovarian carcinomas. Different theories have been postulated in order to explain the development of port site metastases during laparoscopy for oncological patients. CONCLUSIONS: Patient selection is an essential factor that can influence the incidence of port site metastases in gynecological patients. Robust data regarding port site metastases in gynecologic oncology are needed. PMID- 29786998 TI - Alloplastic breast reconstruction after mastectomy. AB - The aim of reconstruction with expanders is to restore breast shape and volume as close as possible to the contralateral breast and to reconstruct the inframammary fold with adequate ptosis. PMID- 29786999 TI - The effects of bortezomib alone or in combination with 5-fluorouracil on proliferation and apoptosis of choriocarcinoma cells. AB - PURPOSE: To investigate the effects of bortezomib alone and in combination with 5 fluorouracil (5-FU) on proliferation and apoptosis in the human choriocarcinoma cell line JEG-3. MATERIALS AND METHODS: Cells were treated with bortezomib, 5-FU or with a combination. Proliferation and apoptosis were measured. NF-iB protein expression was examined using immunofluorescence. RESULTS: Following treatment with ten nM bortezomib, rates of apoptosis were significantly higher than controls (p < 0.05) and NF-kB expression increased. 5-FU at 0.025 MUg/ml or 0.25 MUg/ml resulted in 60.1 +/- 0.4% and 67.0 +/- 0.2% growth inhibition, respectively, an increase compared to individual treatment (p < 0.05). Apoptosis in cells treated with bortezomib +5-FU was significantly higher than either treatment alone (p < 0.05). Inhibition of proliferation by the combination treatment was synergistic. CONCLUSION: Bortezomib alone or in combination with 5 FU inhibited JEG-3 cell proliferation and induced apoptosis by increasing NF-kB expression. Combination treatment exerted synergistic effects on growth inhibition. PMID- 29787000 TI - Negative pressure wound treatment (NPWT) in vulva and groin wounds in gynaecologic oncology. AB - : Secondary healing of complicated vulvar and groin wounds is a major challenge due to its moist condition and at risk of contamination by colonic flora. Vacuum assisted closure is the controlled application of sub-atmospheric pressure to the local wound environment using a sealed dressing connected to a vacuum pump. MATERIALS AND METHODS: The NPWT consists of an open-pore polyurethane ether foam sponge, an adhesive cover, fluid collection system, and suction pump that generates negative pressure. Direct application of sponge to blood vessels, bone, nerves or intact skin is avoided. The dressing and tubing are changed every 48-72 hours. RESULTS: Eight patients had NPWT following the vulva and/or groin surgery. Pain during removal of the sponge was the main adverse event requiring narcotic analgesia. All wounds healed completely. One patient is dead of disease progression. Others are alive without disease at four to 48 months. CONCLUSION: Wound breakdown in vulvar and groin surgery is an infrequent occurrence because of the rarity of full radical excision for vulva cancer and infralevator pelvic exenterative surgery. The present experience with NPWT was favourable. PMID- 29787001 TI - Secondary cytoreductive surgery, hyperthermic intraperitoneal intraoperative chemotherapy, and chemotherapy alone: a retrospective comparison of alternative approaches in relapsed platinum sensitive ovarian cancer. AB - INTRODUCTION: The best treatment for relapsed platinum sensitive epithelial ovarian cancer (EOC) is controversial. The aim of the study was to compare progression-free survival (PFS) and overall survival (OS) in platinum-sensitive EOC patients treated with chemotherapy alone (CTA), secondary cytoreductive surgery (SCR) or SCR plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective analysis of the clinical outcome of 46 EOC patients with at least 30 months of follow-up. RESULTS: Median follow-up time was 32 months for the CTA group, 30 months for the SCR group, and 45 months for the SCR + HIPEC group. Fifteen recurrences were observed in the CTA group, seven in the SCR group, and 16 in the SCR + HIPEC group. The median time elapsed between first and second recurrence (PFI-2) was significantly higher among patients treated with SCR + HIPEC, in comparison with patients treated with CTA (p = 0.012 andp = 0.017, respectively). On the contrary, PFI-2 did not significantly differ between the SCR and SCR + HIPEC groups (p = 0.877). A statistically significant difference in OS favouring SCR + HIPEC in comparison with CTA (p = 0.04) was observed. CONCLUSIONS: SCR HIPEC compared with CTA improves PFI-2 in patients with platinum-sensitive EOC recurrence. SCR + HIPEC might also improve OS in comparison with CTA. No improvement in favor of SCR + HIPEC vs SCR was observed,. These results further support the need of a randomized trial comparing chemotherapy with SCR +/- HIPEC in this setting. PMID- 29787002 TI - HPV 16 and 18 viral loads are greater in patients with high-grade cervical epithelial lesions. AB - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide. High-risk infection with HPV type 16 or type 18 is the most important risk factor associated with the development of cervical cancer. AIMS: To determine the viral load of HPV-16 and HPV-1 8 in samples from women with cervical epithelial lesion in the State of Colima, Mexico. MATERIALS AND METHODS: A cross-sectional analytic study was conducted that included 45 samples positive for HPV- 16 and 45 samples positive for HPV-1 8 from patients with cervical cancer or precursor lesion. Real time PCR was employed to determine the number of copies /101 cells. Viral load was determined in the two groups of patients and correlated with tumor grade. RESULTS: THe authors found that the HPV-1 6 viral load was greater than that of HPV-18 through a Mann-Whitney U analysis, resulting in ap = 0.000; as the malignancy of the cervical lesion progressed, the viral load increased, and HPV 16 showed a moderate positive association with an r = 0.509 and a p = 0.000, whereas HPV-18 showed a weak positive correlation with an r = 0.372 and a p = 0.0 12. CONCLUSIONS: The viral load of HPV-16 was greater than that of HPV-18. The HPV-16 viral load had a moderate positive association in relation to cervical lesion severity, whereas the viral load of HPV- 18 had a weak positive correlation with respect to the cervical lesion grade. PMID- 29787003 TI - HPV16 E6 mutations and p53 codon72 polymorphism among women with cervical intraepithelial neoplasia 2 and 3 in China. AB - OBJECTIVE: To study the distribution of HPV16 E6 gene mutations and p53 codon72 polymorphism among women with HPV16+ cervical precancerous lesions and explore their relationship with the risk of cervical intraepithelial neoplasia (CIN) 2, 3. Materials and Meth- ods: This study analyzed a total of 112 cases of exfoliated HPV16+ cervical cell specimens which were divided into group I (normal and CIN1, 55 cases) and group2 (CIN2, 3, 57 cases). Among the 112 specimens, 85 cases were successfully amplified for HPV E6 gene by PCR and the PCR products were sequenced directly. P53 codon72 region was also amplified from the 112 specimens and the PCR products were sequenced directly and compared with the standard sequence. RESULTS: Among the 85 amplified HPV sequences, point mutations such as T178G, T350G, G132A, A442C, T310G, G94T, C551A, etc. were found, among which, T178G showed the highest rate (51.76%). The rate of HPV16 E6 mutation T178G in CIN2, 3 group was significantly higher than that in normal and CINI group, i.e., in the 112 amplified p53 codon72 sequences, the distribution of Pro/Pro genotype in normal, and CIN1 group was significantly different from that in CIN2, 3 groups, and the disease risk of Pro/Pro genotype was much higher than that of Arg/Arg and Arg/Pro genotypes. CONCLUSION: HPV16 E6 T178G mutation increases the disease risk of CIN2, 3. Meanwhile, compared with Arg/Arg and Arg/Pro genotypes, p53 codon72 Pro/Pro genotype more associated with the disease risk of CIN2, 3. PMID- 29787004 TI - Effects of salvianolic acid B on growth inhibition and apoptosis induction of ovarian cancer SKOV3. AB - OBJECTIVE: To explore the influence of salvianolic acid B (Sal B) on cell proliferation and apoptosis of ovarian cancer cell line SKOV3, livin, and caspase 3 gene expression. MATERIALS AND METHODS: Ovarian cancer cell line SKOV3 was cultured in vitro and the cell proliferation was detected by MTT method. Cell apoptosis and cell cycle were measured by Annexin V/PI flow cytometry. Karyon morphology was observed by Hoechst33258 fluorescence staining. Livin and caspase 3 expressions were assayed using western blot. RESULTS: Sal B with different concentrations had an inhibition effect on growth of SKOV3 in vitro and the inhibitory effect was strengthened with the increase of Sal B concentration, which showed an obvious dose-effect relationship and the half inhibitory concentration (IC50) was 45.6 MUmol/L. The proportion of GO/GI phase increased and that of S phase decreased after treatment with Sal B. In addition, the apoptosis rate increased significantly with the increasing of Sal B concentration. Results of Hoechst33258 fluorescence staining showed that cell apoptosis appeared after effect of Sal B with the characteristics of cell shrinkage, appearing vacuoles in cells, condensed chromatin and fracture, etc. Sal B had some inhibitory effects on livin expression in SKOV3 cell but promoted the expression of caspase-3. The corresponding effects were enhanced with the increase of drug dosage. CONCLUSIONS: Sal B has obvious effects on inhibiting growth and promoting apoptosis of ovarian cancer SKOV3 cell, which may be realized by downregulating livin expression, upregulating caspase-3 expression, and blocking the cell cycle. PMID- 29787005 TI - Concomitant chemoradiation treatment in selected Stage I endometrioid endometrial cancers. AB - PURPOSE OF INVESTIGATION: To evaluate chemotherapy with concomitant radiotherapy (RT) in "high risk" endometrial cancer (EC) patients. Furthermore to develop a new algorithm for management and treatment. MATERIALS AND METHODS: The study included 182 Stage I endometrioid EC patients who underwent definitive surgery after a first treatment. Stage, grade, ploidy DNA index, lymphovascular space involvement (LVSI), tumor diameter (TD), and p53 were considered to identify "high-risk" patients. Twenty-seven women received adjuvant concomitant chemoradiation (CR). Toxicity related to the CR treatment, disease free interval (DFI), and status of the patients were considered. RESULTS: Twenty-seven patients according to the present algorithm treatment were considered at "high risk". Median follow up was 43 months (range 16-68). Twenty-five (92%) patients completed CR treatment. Overall, grade 3/4 hematological toxicity was 18% while gastrointestinal toxicity was 15%. Four patients relapsed with a five-year rate of 14% of recurrences. CONCLUSIONS: Adjuvant concomitant CR is well tolerated and is a feasible regimen in "high risk" patients. The authors' new algorithm treatment could be used for management and further clinical studies. PMID- 29787006 TI - Risk factors of node metastasis in cervical carcinoma. AB - : Purpose ofinvestigation: To investigate the metastatic risk factors of pelvic lymph nodes in patients with cervical carcinoma in Stage Ia2 and IIa2. MATERIALS AND METHODS: The clinic pathologic parameters in 337 patients with Stage Ia2-IIa2 cervical carcinoma were retrospectively analyzed. The risk factors for pelvic lymph node metastasis were evaluated by the way of univariate X2 statistic analysis and binary logistic regression analysis. RESULTS: The lymph nodes metastasis rate was 11.87% (40/337). Single variable analysis showed that age, clinical stage, the size of tumor >= four cm, depth of stromal invasion 2/3, lymph-vascular space involvement (LVSI), and parametrial extension were related to the metastasis of lymph nodes. Multivariate analysis showed that the size of tumor, depth of stromal invasion, LVSI, and parametrial extension were independent risk factors. CONCLUSION: Patients with tumor size >= four cm, stromal invasion >= 2/3, LVSI, and parametrial extension were at high risk of lymph node metastasis. PMID- 29787007 TI - Distant metastases from invasive lobular breast carcinoma classic type - treatment and prognosis. AB - INTRODUCTION: Invasive lobular carcinoma (ILC) comprises 4-15% of all malignant neoplasms of the breast. The "classical variant of ILC" (C-ILC) constitutes some 60-80% of this cancer. The main cause of treatment failures is dissemination observed in 8-38% patients The disant metastases (DM) are frequently localized in: bones, gastrointestinal tract, uterus, leptomeninges, and ovaries. The aim of this study was to present the methods and results of the treatment of patients with DM from the classical variant of ILC (C-ILC) at a single institution in Poland. MATERIALS AND METHODS: Between January 1983 and December 2004, 210 women with C-ILC of the breast were primarily treated surgically (mastectomy in 182 (86.7%) patients and breast conserving therapy in 28 (13.3%) patients). Then adjuvant therapy (radiotherapy, chemotherapy, and hormonotherapy) was applied according to presence of clinical indications. RESULTS: The present study focused on a group of 41 patients with a median age of 59 that died with DM from C-ILC during the ten-year follow-up. This failure developed on average 65 months (3 186) after surgery of ILC. The most frequently DM developed: bones (39.1%), GI (small bowell, stomach, colon, rectum) - 31.8%, and reproductive organs (ovary, uterus) - 19.1%. In therapy of DM, different configuration surgery, radiotherapy, and chemo-hormonotherapy were used. The median survival after the diagnosis of DM was connected with localization of distant metastases. CONCLUSION: Patients with classic variant of infiltrate lobular cancer of breast should be regularly follow up, which could permit early diagnosis of distant metastases and improve treatment results. PMID- 29787008 TI - Laparoendoscopic single-site surgery for the assessment of peritoneal carcinomatosis resectability in patients with advanced ovarian cancer. AB - PURPOSE OF INVESTIGATION: To evaluate the feasibility, safety, and effectiveness of laparoendoscopic single site surgery (LESS) for the assessment of peritoneal carcinomatosis resectability in patients with advanced stage ovarian cancer (AOC). MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of patients affected by advanced stage ovarian cancer who underwent LESS for operative work-up. A standard cytoreductive laparotomy surgery (CRS) was performed. RESULTS: Fifty-two women affected by AOC underwent LESS for operative work-up. The peritoneal cancer score was completed in 49 (94%) patients by use of LESS; 34/37 (92%) patients considered with a resectable disease were effectively optimally debulked and 15/52 (28%) patients considered with an unresectable disease received before neoadjuvant chemotherapy (NACT) and then underwent surgery. CONCLUSION: LESS is feasible, safe, and is an alternative minimally invasive procedure to assess the resectability of AOC patients. PMID- 29787009 TI - Effect of exemestane on the invasive growth of endometrial carcinoma HHUA cells. AB - OBJECTIVE: To investigate the effect of exemestane on HHUA human endometrial carcinoma cells. MATERIALS AND METHODS: The HHUA human endometrial carcinoma cells were treated with various concentrations of exemestane, and its effects on cell growth and apoptosis were investigated in vitro. The cell apoptosis was analyzed by flow cytometry and RT-PCR was used to investigate the expression of CD44s. The invasion ability of HHUA human endometrial carcinoma cells which treated with exemestane were assessed using transwell chamber model. RESULTS: At increasing doses of exemestane, a simultaneous increase in apoptotic subpopulations was detected when compared with group A (p < 0.05); the CD44s expression was found to be suppressed after the exemestane treatment. The decrease was a dose-dependent with exemestane treatment. CONCLUSION: 6x108 mol/L exemestane is an optimal dose to inhibit the expression of CD44s mRNA and inhibit the invasive growth of the endometrial carcinoma HHUA cells. PMID- 29787010 TI - Histopathological correlation of splenic disease with radiological and surgical findings: should we incorporate splenectomy into standard procedures for disseminated Millerian adenocarcinoma? AB - PURPOSE OF INVESTIGATION: To determine the positive predictive value (PPV) of both preoperative radiological and intraoperative identification of splenic disease in cases of advanced and recurrent gynaecological malignancy. MATERIALS AND METHODS: A retrospective study of all splenectomies performed during surgeries for disseminated gynaecological malignancy at the Pan Birmingham Gynaecological Cancer Centre between May 21st, 2008 and January 31st, 2015. RESULTS: Forty-one women were identified, most of whom had Stage 3C, high grade, serous Milllerian adenocarcinomas. Thirty-seven (90.2%) spleens were removed because of intraoperative suspicion of disease and the remaining four (9.8%) were removed following inadvertent injury. No spleens were detected radiologically that did not have obvious macroscopic disease. The PPV for the preoperative and intraoperative detection of splenic disease were 88.9% and 91.9%, respectively. Half of the spleens removed following inadvertent injury had disease identified following histopathological examination. CONCLUSION: Intraoperative identification of splenic disease correlates well with histopathological examination. However, in 50% of splenectomies performed following inadvertent trauma and where disease was not suspected, metastases were identified. PMID- 29787011 TI - P16INK4a as a progression/regression tumour marker in LSIL cervix lesions: our clinical experience. AB - PURPOSE OF INVESTIGATION: The aim of this prospective study was the evaluation of low-grade intraepithelial lesion (LSIL) lesions evolvement in woman with evidence of high risk HPV infection and p 16 4a negative expression. MATERIALS AND METHODS: 150 women with cytological diagnosis of LSIL were selected to be underwent to three years of follow-up consisting in smear test, colposcopy, and protein p16I4a investigation every six months and HPV-test every 12 months. RESULT: Final follow-up showed 45 cases of spontaneous lesion regression and 42 cases of persistence with absence of protein p164NK4a in all of them. There were three cases of disease progression to CIN2, two at 18-month follow-up and one at last follow-up. Disease progression was characterized of p16NK4a expression. CONCLUSION: p16l4a should help to identify which LSIL cases are inclined to the progression of the disease and focalize which patients are eligible for specific treatment. PMID- 29787012 TI - CLC-3 Cl- channel-mediated invasion and migration of human ovarian cancer cells. AB - OBJECTIVES: To investigate the potential role of CLC-3, a member of the voltage gated chloride channel (CLC) superfamily, in invasion and migration of ovarian cancer cell line SKOV3. MATERIALS AND METHODS: CLC-3 antisense oligonucleotides were transfected into ovarian cancer cell line SKOV3, and its effects on cell invasion and migration were analyzed by using Transwell chamber assay and wound healing assay in vitro. The efficiency of CLC-3 antisense was determined with RT PCR and Western blotting. The protein concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) were determined using ELISA kits. Cell volume measurements were performed. RESULTS: Studies in vitro revealed that the CLC-3 antisense inhibited invasion and migration of ovarian cancer cell line SKOV3. CLC-3 antisense treatment decreased protein levels of MMP-2, MMP-9, and VEGF in culture medium of SKOV3 cells. In addition, the authors found that the capability for regulatory volume decrease (RVD) was much attenuated in SKOV3 cells transfected with CLC-3 antisense. CONCLUSIONS: These results strongly suggest that CLC-3 may get involved in proliferation, invasion, and migration of ovarian cancer cells and thus may be a useful therapeutic target. PMID- 29787013 TI - The trend of chemotherapy-induced peripheral neurotoxicity in ovarian cancer survivors and its impacts on daily life during and one year after treatment. AB - PURPOSE: To explore the trend of progression and regression of peripheral neuropathy (PN) induced by combination of carboplatin and paclitaxel, and the impacts on daily activities. MATERIALS AND METHODS: PN was evaluated by nurse based interview and patient-reported measures in their diary. The severity of PN scaled by National Cancer Institute Common Toxicity Criteria (NCI-CTC) before each cycle of chemotherapy and at three, six, and 12 months after drug withdrawal and coded as Grade I - V. RESULTS: The authors enrolled 106 eligible patients with ovarian cancer who underwent six cycles of combined chemotherapy of carboplatin plus paclitaxel. No patients showed Grade IV and V of PN and it was gradually aggravated following the dose accumulation. About 29.3% of the patients presented no PN, 64.2% Grade I, and 6.6% Grade II after the third course of chemotherapy, but increased to 36.8% of Grade I, 25.5% of Grade II, and 34.9% of Grade III after the sixth course of chemotherapy. At one-year follow-up, the rate of PN still existed with the rate of 88.5%, 57.3%, and 38.7% at three, six, and 12 months after drug withdrawal. Thirty-one patients encountered accidents, such as sharp injury (14.2%), fall (9.4%), burn (3.8%), and cold injury (1.9%). CONCLUSIONS: A significant proportion of patients with epithelial ovarian cancer treated with carboplatin plus paclitaxel suffer long term neuropathy and it affects patient's daily activities. Specialized care is necessary to provide not only during treatment, but also months to years after drugs withdrawal. PMID- 29787014 TI - Polymorphism of the CYP2D6 gene in women with breast cancer treated with tamoxifen. AB - OBJECTIVE: To evaluate polymorphism frequency of the CYP2D6*4, *10, and * 17 alleles in women with breast cancer treated with tamoxifen. MATERIALS AND METHODS: Ninety-five women with estrogen and progesterone receptor-positive breast carcinoma were investigated from September to December 2013. A three-ml sample of peripheral blood was collected from each patient to analyze the presence of CYP2D6 *4, *10, and *17 allele polymorphism by specific polymerase chain reaction technique (PCR) for analysis of haplotypes *1, *4, *10, and *17, determined by studies of different single-nucleotide polymorphism (SNP). The data obtained were compiled and analyzed with the aid of Excel software 2010. RESULTS: The frequency of CYP2D6 alleles *4, *10, and *17 was 16%, 29%, and 2%, respectively, and haplotype * 1/*10 was shown in 22% of the women. The phenotype of intermediate metabolism occurred in 8% of women. CONCLUSIONS: The present study showed a deficiency in tamoxifen metabolism, characterized by intermediate metabolism in 8% of Brazilian women. PMID- 29787015 TI - Clinical efficacy analysis of preoperative neoadjuvant chemotherapy with high dose dense paclitaxel plus cisplatin in Stages IB2, IIA2, IIB cervical cancer in Iran. AB - PURPOSE OF INVESTIGATION: In Iran, the authors use neoadjuvant chemotherapy (NACT) prior to surgery in cervical cancer due to limited access to the radiotherapy and very prolonged waiting time in accession to radiotherapy. The study was done to analyze the efficacy of the NACT with high dose-dense paclitaxel and cisplatin before radical surgery on cure rate, survival rate, and the progression of free survival rate of bulky tumor of cervical cancer in Stages 1B2, IId A2, and IIB. MATERIALS AND METHODS: Fifty-two patients with cervical cancer in Stages Ib2, IIA2, and IIB were selected, and responding patients to chemotherapy were scheduled to undergo radical hysterectomy and bilateral pelvic lymphadenectomy with or without para-aortic lymphadenectomy. RESULTS: Fifty out of 52 patients with a median age of 50 years were evaluable for clinical response. Thirty-two patients (64%) responded to the NACT including six (12%) with a complete clinical response. There was no statistical relationship between clinical response, tumor stage and size, and parametrical involvement, however, patients with higher grade of tumor, adenocarcinoma or tumor in upper 2/3 of vagina showed a higher probability of no response to chemotherapy. Downstaging after NACT in all stages was statistically significant regarding pathologic findings and clinical response (p = 0.002). Five-year survival was 88% and factors affecting survival and disease-free survival were pathological response and tumor site based on cox-regression analysis. Overall recurrence rate was 20% and tumor size was the only significant relevant factor for recurrence (p = 0.017). CONCLUSION: Combined regimen of chemotherapy in locally advanced cervical cancer proved to be valuable and efficacious without any late complications. PMID- 29787016 TI - A case of ovarian small cell carcinoma of the pulmonary type that was observed as it developed. AB - INTRODUCTION: In the case reported here, the authors observed ovarian small cell carcinoma of the pulmonary type as it developed. CASE: The patient was a 48-year old woman who underwent a hysterectomy for CIN3 in 2007. A year later, the woman underwent screening for ovarian cancer. A gradually growing ovarian mass was noted. This mass was found to be a mixed tumor. This mixed tumor grew to 36 mm in size, and six months later it had enlarged to 119 mm. After surgery, the tumor was pathologically diagnosed as an ovarian small cell carcinoma of the pulmonary type with a neuroendocrine nature that was positive for CD56 and synaptophysin. Postoperatively, the patient received six courses of combined therapy with irinotecan and cisplatin (CPT-P therapy), and the patient has survived disease- free for over two years. CONCLUSION: Findings suggested that ovarian small cell carcinoma of the pulmonary type is a type I ovarian malignancy that develops through an adenoma-carcinoma sequence. PMID- 29787017 TI - Importance of differential diagnosis post-treatment of adenocarcinoma of the uterine cervix: a case report of sarcoidosis. AB - OBJECTIVE: To report a case of sarcoidosis post-treatment of adenocarcinoma of the uterine cervix. CASE: A 38-year-old, GlPlAO was admitted to the present hospital for palliative treatment of Stage IB 1 adenocarcinoma of the uterine cervix with hepatic recurrence post- hysterectomy. The patient initially received six cycles of cisplatin and taxol leading to complete remission. Six months after the palliative treatment, MRI revealed slight changes in the pelvis, suggestive of the involvement of the left iliac lymph node. Anatomo-pathological results after lymphadenectomy showed tumor recurrence. Following additional pelvic radiotherapy, the patient remained asymptomatic. However, oncologic control performed three months later exposed mediastinal lymphadenopathy and new biopsy revealed sarcoidosis. The patient remained asymptomatic in the subsequent follow ups without evidences of tumor recurrence. This study shows the importance of differential diagnosis during the oncologic monitoring of cervical cancer patients to avoid unnecessary treatments at the expense of better therapeutic options. PMID- 29787018 TI - Primary vaginal endometrial stromal sarcoma associated with endometriosis: a case report with a review of the literature. AB - Extrauterine endometrial stromal sarcomas (ESSs) are quite rare tumors, and vagina is an unusual site for these tumors. This paper presents a very rare pathological entity of primary vaginal ESS. A 46-year-old woman with a complaint of postcoital vaginal bleeding, low abdominal pain, and constipation was admitted to the clinic. She had a mass of seven cm in size, located in the posterior fornix detected on physical examination. The preoperative biopsy showed ESS, surgical material, and evaluation of an endometrium confirmed the diagnosis of primary vaginal ESS. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial vaginectomy. The diagnosis of ESS performed by pathologic and immunohistochemical evaluation was: caldesmon (-), actin (-), desmin (-). CDIO (+), ER (+), PR (+), and vimentin (+). There was no ESS lesion in the endometrium. The patient was free of tumor for 22 months after the surgery without any additional therapy. In this study, the authors report the sixth case of primary vaginal ESS in the literature and aim to discuss diagnostic criteria and management protocols in the light of the literature. PMID- 29787019 TI - Apocrine carcinoma of the vulva. Case report and review of literature. AB - OBJECTIVES: To report a case of apocrine adenocarcinoma of the vulva and introduce the sentinel node dissection as a method to diagnose it. MATERIALS AND METHODS: Description of a case of a 77-year-old woman with histological diagnostic of apocrine adenocarcinoma of the vulva and literature review of the 16 cases published from 1954 to nowadays. RESULTS: Treatment of vulvar apocrine carcinoma is controversial given its low incidence and the small number of cases which have been reported. CONCLUSION: Selective sentinel lymph node biopsy may provide a valid option in selected patients to decrease their clinical complications. PMID- 29787020 TI - Uterine tumors resembling ovarian sex cord tumors: a case report with adenomyosis and complex hyperplasia with atypia. AB - Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are very rare uterine neoplasms. They mostly behave in a benign fashion but cases were reported with extra-uterine spread. There are less than 50 cases reported in the literature so far according to the present authors' knowledge. We report a case of 45-year-old woman with UTROSCT concurrent with adenomyosis and complex hyperplasia with atypia of endometrium and her three-year follow up. PMID- 29787021 TI - Growing teratoma syndrome: an unusual evolution of treated ovarian immature teratoma - a case report. AB - Growing teratoma syndrome (GTS) is a rare condition among germ cell tumor (GCT) patients during treatment with systemic chemotherapy. It is characterized by the development of enlarging masses, the normalization of tumor markers, and the presence of only mature teratoma in the pathological specimen. The authors present the unusual case of a 15-year-old girl with an immature teratoma treated with conventional surgery and systemic chemotherapy. On her follow up, although tumor markers returned to normal, there was an enlargement of abdomino-pelvic masses confirmed by a PET/TC study. With the diagnosis of a GTS, the patient underwent a com- plete cytoreduction. Histologically, all the specimens contained mature teratoma tissue. The patient remains clear with no signs of recurrence with no further treatment. The knowledge and awareness of this syndrome are highlighted in order to prevent further unnecessary chemotherapy and allow an optimal cytoreduction, which seems to be the most effective therapy so far. PMID- 29787022 TI - An unusual ovarian neoplasm diagnosed in a patient with rupture of unicornuate uterus during pregnancy: a case report. AB - Unicornuate uterus is a rare disease characterized with reduced fertility, and ovarian tumor diagnosed during pregnancy is uncommon as well. These two diseases have been reported separately. However, patient suffering from both diseases has never been reported before. The authors herein report a case of a 32-year-old Chinese woman presenting with a unicornuate uterus with no horn, who suffered from acute abdominal pain and intra-abdominal hemorrhage at 26 weeks gestation. Incidentally, a borderline ovarian tumor (BOT) and rupture of uterus were found during an urgent exploratory laparotomy. During the follow-up, ovarian tumor recurred in the first year after the operation. The authors suggest that BOT with micropapillary patterns should be paid much more attention to, other than only assessing the histological type. Furthermore, they also suggest that a slightly increased in serum CA-125 value should not be ignored. PMID- 29787023 TI - Selective arterial embolisation for intractable vaginal haemorrhage in genital tract malignancies. AB - PURPOSE OF INVESTIGATION: Embolisation of the internal iliac artery has been described as an effective and safe method of treating massive vaginal haemorrhage in small series of advanced uterine cancer and case reports of cervical cancer. Selective embolization of the bleeding vessel is potentially less morbid. The aim of this study was to assess the efficacy of selective arterial embolisation (SAE) in controlling intractable haemorrhage due to gynaecological malignancy. MATERIALS AND METHODS: This retrospective observational study comes from in a tertiary cancer center with 300 new gynecologic cancers per annum. The authors reviewed all gynecology cancer patients who had intractable major vaginal haemorrhage in the first five years following the introduction of selective arterial embolisation at their unit. The outcomes measured were the control of acute haemorrhage and discharge to planned pathway of treatment. RESULTS: SAE was successful in all cases. Identification of the bleeding point facilitated highly selective embolisation in more than half of the patients. The uterine arteries were embolised in the remaining cases. Bleeding stopped immediately. The expedient control of haemorrhage facilitated early discharge to commencement/continuation of radiation treatment or palliative care as appropriate. CONCLUSIONS: Since the introduction of SAE the authors have avoided emergency radiotherapy, surgery, and repeat vaginal packing in patients with intractable vaginal bleeding due to gynaecological cancer. Patients were discharged to their appropriate treatment pathways in a timely manner. The authors recommend the application of SAE. PMID- 29787024 TI - An unusual enhanced Doppler vascular profile of a rare uterine tumor: PEComa. AB - PEComas represent a rare class of mesenchymal tumors, with different primary locations. There are less than 100 cases of uterine PEComas published in English literature until now and information considering imaging features of these PEComas is very limited, focusing on CT and MRI and not as much on ultrasounds (US). The authors present here a case of rapidly growing uterine PEComa, with local invasive potential and recurrence, and the review of literature on US characteristics of PEComas. Harboring a hyperechogeneous heterogeneous aspect with no clear separation from the adjacent uterus on the whole boundary, with an extremely rich central vascular network, with low impedance and a rapidly growing profile, this tumor does not show the classic US appearance of malignant PEComas, which are generally easily confused with leiomyomas. However, even if this pattern did not allow the authors to anticipate the histopathological result, it offered clear clues about its invasiveness potential. PMID- 29787025 TI - Mayer-Rokitansky-Kuster-Hauser syndrome accompanied by invasive ductal carcinoma: a case report. AB - Milllerian agenesis and the absence of organs of Millerian canal origin are referred to as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Invasive ductal carcinoma constitutes 47-75% of all breast carcinomas and is the most common type. The authors report the first case of invasive ductal carcinoma associated with MRKH syndrome in the literature to their knowledge. A 25-year-old woman with a palpable mass in her right breast for three months presented to the presented clinic. On physical examination a mobile, firm mass measuring 2x2 cm was detected in right breast, at a region close to axilla. A fine needle aspiration biopsy from the lesion revealed malignant cells and thus a segmental mastectomy operation was performed. All genital tract and endocrinological system should be thoroughly examined before administering hormone replacement therapy to patients presenting with primary amenorrhea.The co-occurrence MRKH syndrome of with invasive ductal carcinoma is regarded as coincidental. Confirming the absence of a common etiology, however, requires further genetic studies. PMID- 29787027 TI - Malignant mixed germ cell tumor of ovary presenting as advanced disease in an adolescent girl. AB - Mixed germ cell tumors are very rare in young females. Patient survival, preservation of ovarian function and fertility are becoming an important issue. A locally advanced (III), bulky malignant mixed germ cell tumour in a 12-year-old girl presented to the Department of Radiotherapy, Regional Institute of Medical Sciences, Imphal, Manipur, in January 2011 with abdominal distension for one month. On physical examination, there was a large lower abdominal mass approximately 16x 14 cm2. Abdominal and pelvic CTs showed a lobulated 19x 15x10 cm soft tissue attenuation mass lesion in the pelvis extending superoanteriorly to supra-umbilical area. Laboratory investigations revealed increased serum LDH (4,245 IU/ L) and serum P-hCG (105.4 mIU/ml). Ultrasonography (USG)-guided fine needle aspiration cytology (FNAC) from left ovarian mass was suggestive of malignant germ cell tumour. In view of bulky and advanced stage, patient was administered four cycles of neoadjuvant chemotherapy (inj. ifosphamide 1,440 mg, inj. etoposide 90 mg, inj. cisplatin 24 mg for D1 -5, four weekly) followed by left salpingo-oophorectomy with wedge biopsy of right ovary and partial omentectomy, and another two cycles of adjuvant chemotherapy with same regimen. Biopsy tissue histopathology report also confirmed mixed germ cell tumour. Patient was kept on regular follow-up and she has been disease-free for the last four years. The present authors' treatment policy in such bulky and advanced tumor in adolescents is effective. PMID- 29787028 TI - The Dental Team Concept and Where the CDHC and Dental Therapist Fit In. PMID- 29787026 TI - Abdominal wall mixed malignant germ cell tumor: a case report and review of literature. AB - Abdominal wall mass is not uncommon in clinic, but it is very rare that germ cell tumors (GCTs) arise in the abdominal wall. The authors review the case of a 34 year-old female with abdominal wall mixed malignant GCT composed of embryonal carcinoma and teratoma and combine the relative literature to explain why GCTs originate from anterior abdominal wall. PMID- 29787029 TI - An Announcement from the ADA Council on Ethics, Bylaws and Judicial Affairs. PMID- 29787030 TI - The EPA Releases Final Rule Requiring Dental Practices To Use Amalgam Separators. PMID- 29787031 TI - How to Get the Word Out that Your Dental Practice is on Social Media. PMID- 29787032 TI - D-DENT Suooort for Veterans. PMID- 29787033 TI - Prescription Drug Misuse and Abuse: A National Health Crisis. PMID- 29787034 TI - Critical preparation and readiness to support future change. AB - The challenging nature of change is well documented and adequate preparation before implementing a change initiative is critical to reducing resistance and increasing its chances of success. This article describes a service review conducted in preparation for possible change and improvement at an internationally ranked school of nursing and midwifery in an Irish tertiary education institution. The purpose of the review was to examine organisational structures and work activities, including pressures facing the administrative team that supports the school, and to establish whether operations were fit for purpose and capable of continuing to support the international ranking. The article outlines the importance of change to maintain a competitive edge and the critical role of leadership during change. The background and rationale for the service review are discussed along with the methods used to prepare staff. The article also reports outcomes of the surveys and focus groups undertaken and discusses the main recommendations and changes implemented so far. It also suggests how the outcomes are relevant to clinical practice. PMID- 29787035 TI - Hair toe tourniquets: a review of two case studies. AB - Digit hair tourniquets are relatively uncommon. There are reports in the literature of hair tourniquets involving other appendages, such as the penis and uvula, however the phenomenon is not widely recognised and is often overlooked by healthcare professionals. This article discusses two case studies in which hair was responsible for creating a tourniquet around a digit. The article explores possible causes and management options for patients, with reference to the case studies. Midwives and health visitors are central to minimising the risk of injury to children as they can educate expectant mothers about this potential problem. PMID- 29787036 TI - Reflections of a black African insider researcher. AB - BACKGROUND: There is a growing body of literature providing reflective accounts and critical examination of the challenges faced by insider researchers. However, there is little research about the specific challenges that black African insider nurse researchers face. AIM: To reflect on the complexities black African insider nurse researchers face in the context of research sites, participants and the interpretation of data. DISCUSSION: Insider researchers are susceptible to various entanglements and dilemmas. Belonging to the same racial and cultural backgrounds as participants is advantageous, although caution is needed. Adoption of the emergent reflective model as an archetypal template can help future insider researchers considerably. CONCLUSION: Being an insider researcher comes with advantages and disadvantages. Entanglement and role ambiguity are some of the disadvantages. However, unspoken understandings with the participants provide insightful meanings into their experiences. IMPLICATION FOR PRACTICE: Reflectivity is crucial to the quality and rigour of qualitative studies. The challenge for future insider researchers is to show explicit awareness, tactfulness, sensitivity, commitment and rigour in their research. PMID- 29787037 TI - Effects of Perinatal Exposure to Dibutyltin Chloride on Fat and Glucose Metabolism in Mice, and Molecular Mechanisms, in Vitro. AB - BACKGROUND: The organotin dibutyltin (DBT) is used in the manufacture of polyvinyl chloride (PVC) plastics, in construction materials, and in medical devices. Previous animal studies showed detrimental effects of DBT during in utero development at relatively high doses, but little was known about the effects of DBT exposure at environmentally relevant doses on endpoints such as obesity and metabolic disease. OBJECTIVES: We tested the potential obesogenic effects of DBT using in vitro and in vivo models. METHODS: We evaluated the effects of DBT on nuclear receptor activation and adipogenic potential using human and mouse multipotent mesenchymal stromal stem cells (MSCs). We also evaluated the effects of perinatal exposure to environmentally relevant doses of DBT in C57BL/6J mice. RESULTS: DBT activated human and mouse PPARgamma and RXRalpha in transient transfection assays, increased expression of adipogenic genes, promoted adipogenic differentiation and increased lipid accumulation in mouse and human MSCs, in vitro. DBT-induced adipogenic differentiation was abolished by the PPARgamma antagonist T0070907, indicating that DBT was acting primarily through PPARgamma. Perinatal exposure to low doses of DBT led to increased fat storage, decreased glucose tolerance, and increased circulating leptin levels in male, but not female, mice. CONCLUSIONS: DBT acted as an obesogen by inducing lipid accumulation in human and mouse MSCs through a PPARgamma-dependent pathway. In vivo exposure to biologically relevant doses of DBT during perinatal development led to increased fat storage, elevated leptin levels in plasma, and glucose intolerance in mice. Based on these findings, we posit that monitoring of DBT levels in human samples may aid in understanding and potentially preventing the rising rates of metabolic disorders in human populations. https://doi.org/10.1289/EHP3030. PMID- 29787229 TI - Graphene Glass Inducing Multidomain Orientations in Cholesteric Liquid Crystal Devices toward Wide Viewing Angles. AB - The photonic reflection of a cholesteric liquid crystal (ChLC) device depends on the spatial distribution of the orientations of their helical axes, and many orientation techniques have been developed so far. In this study, we select the hybrids of graphene directly grown on quartz glass as platforms to construct ChLC based devices. This special design makes graphene serve as both an alignment layer and a conductive layer, thus affording a more simplified device fabrication route. We reveal that multidomain structures can be evolved for ChLCs on polycrystalline monolayer graphene on quartz glass, as evidenced by polarized optical microscope characterizations. The disparate orientations of the helical axes of ChLCs and the formation of multidomain structures are proposed to be induced by the different domain orientations of graphene, leading to a wide viewing angle of the ChLC-based devices. Moreover, the pitch of ChLCs is also observed to play a key role in the relative orientations of ChLCs. A wide viewing angle of the ChLC-based device is also detected especially in the infrared spectrum region. Briefly, this work should provoke the application of graphene glass as a perfect transparent electrode in the fabrication of liquid-crystal based devices showing broad application potentials in intelligent laser protection and energy-saving smart windows. PMID- 29787228 TI - Cyanylated Cysteine Reports Site-Specific Changes at Protein-Protein-Binding Interfaces Without Perturbation. AB - To investigate the cyanylated cysteine vibrational probe group's ability to report on binding-induced changes along a protein-protein interface, the probe group was incorporated at several sites in a peptide of the calmodulin (CaM) binding domain of skeletal muscle myosin light chain kinase. Isothermal titration calorimetry was used to determine the binding thermodynamics between calmodulin and each peptide. For all probe positions, the binding affinity was nearly identical to that of the unlabeled peptide. The CN stretching infrared band was collected for each peptide free in solution and bound to calmodulin. Binding induced shifts in the IR spectral frequencies were correlated with estimated solvent accessibility based on molecular dynamics simulations. This work generally suggests (1) that site-specific incorporation of this vibrational probe group does not cause major perturbations to its local structural environment and (2) that this small probe group might be used quite broadly to map dynamic protein-binding interfaces. However, site-specific perturbations due to artificial labeling groups can be somewhat unpredictable and should be evaluated on a site-by-site basis through complementary measurements. A fully quantitative, simulation-based interpretation of the rich probe IR spectra is still needed but appears to be possible given recent advances in simulation techniques. PMID- 29787230 TI - Wave Function Engineering in CdSe/PbS Core/Shell Quantum Dots. AB - The synthesis of epitaxial CdSe/PbS core/shell quantum dots (QDs) is reported. The PbS shell grows in a rock salt structure on the zinc blende CdSe core, thereby creating a crystal structure mismatch through additive growth. Absorption and photoluminescence (PL) band edge features shift to lower energies with increasing shell thickness, but remain above the CdSe bulk band gap. Nevertheless, the profiles of the absorption spectra vary with shell growth, indicating that the overlap of the electron and hole wave functions is changing significantly. This leads to over an order of magnitude reduction of absorption near the band gap and a large, tunable energy shift, of up to 550 meV, between the onset of strong absorption and the band edge PL. While the bulk valence and conduction bands adopt an inverse type-I alignment, the observed spectroscopic behavior is consistent with a transition between quasi-type-I and quasi-type-II behavior depending on shell thickness. Three effective mass approximation models support this hypothesis and suggest that the large difference in effective masses between the core and shell results in hole localization in the CdSe core and a delocalization of the electron across the entire QD. These results show the tuning of wave functions and transition energies in CdSe/PbS nanoheterostructures with prospects for use in optoelectronic devices for luminescent solar concentration or multiexciton generation. PMID- 29787231 TI - Glucose- and H2O2-Responsive Polymeric Vesicles Integrated with Microneedle Patches for Glucose-Sensitive Transcutaneous Delivery of Insulin in Diabetic Rats. AB - Herein, a dual-responsive insulin delivery device by integrating glucose- and H2O2-responsive polymeric vesicles (PVs) with transcutaneous microneedles (MNs) has been designed. This novel microneedle delivery device achieves a goal of fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from a triblock copolymer including poly(ethylene glycol), poly(phenylboronic acid) (glucose-sensitive block), and poly(phenylboronic acid pinacol ester) (H2O2-sensitive block). After loading with insulin and glucose oxidase (GO x), the drug-loaded PVs display a basal insulin release as well as a promoted insulin release in response to hyperglycemic states. The insulin release rate responds quickly to elevated glucose and can be further promoted by the incorporated GO x, which will generate the H2O2 at high glucose levels and further break the chemical links of phenylboronic acid pinacol ester group. Finally, the transdermal delivery of insulin to the diabetic rats ((insulin + GO x)-loaded MNs) presents an effective hypoglycemic effect compared to that of subcutaneous injection or only insulin-loaded MNs, which indicates the as prepared MNs insulin delivery system could be of great importance for the applications in the therapy of diabetes. PMID- 29787232 TI - Self-Assembled Chiral Gold Supramolecules with Efficient Laser Absorption for Enantiospecific Recognition of Carnitine. AB - Stereospecific recognition of chiral molecules is ubiquitous in chemical and biological systems, thus leading to strong demand for the development of enantiomeric drugs, enantioselective sensors, and asymmetric catalysts. In this study, we demonstrate the ratio of d-Cys and l-Cys playing an important role in determining the optical properties and the structures of self-assembled Cys-Au(I) supramolecules prepared through a simple reaction of tetrachloroaurate(III) with chiral cysteine (Cys). The irregularly shaped -[d-Cys-Au(I)] n- or - [l-Cys Au(I)] n- supramolecules with a size larger than 500 nm possessing strong absorption in the near-UV region and chiroptical characteristics were only obtained from the reaction of Au(III) with d-Cys or l-Cys. On the other hand, spindle-shaped -[d/l-Cys-Au(I)] n- supramolecules were formed when using Au(III) with mixtures of d/l-Cys. Our results have suggested that Au(I)...Au(I) aurophilic interactions, and stacked hydrogen bonding and zwitterionic interactions between d/l-Cys ligands are important in determining their structures. The NaBH4-mediated reduction induces the formation of photoluminescent gold nanoclusters (Au NCs) embedded in the chiral -[d-Cys-Au(I)] n- or -[l-Cys-Au(I)] n- supramolecules with a quantum yield of ca. 10%. The as formed Au NCs/-[d-Cys-Au(I)] n- and Au NCs/-[l-Cys-Au(I)] n- are an enantiospecific substrate that can trap l-carnitine and d-carnitine, respectively, and function as a nanomatrix for surface-assisted laser desorption/ionization mass spectrometry (LDI-MS). The high absorption efficiency of laser energy, analyte-binding capacity, and homogeneity of the Au NCs/-[Cys Au(I)] n- allow for quantitation of enantiomeric carnitine down to the micromolar regime with high reproducibility. The superior efficiency of the Au NCs/-[d-Cys Au(I)] n- substrate has been further validated by quantification of l-carnitine in dietary supplements with accuracy and precision. Our study has opened a new avenue for chiral quantitation of various analytes through LDI-MS using metal nanocomposites consisting of NCs and metal-ligand complexes. PMID- 29787233 TI - Controlling the Replication of a Genomically Recoded HIV-1 with a Functional Quadruplet Codon in Mammalian Cells. AB - Large efforts have been devoted to genetic code engineering in the past decade, aiming for unnatural amino acid mutagenesis. Recently, an increasing number of studies were reported to employ quadruplet codons to encode unnatural amino acids. We and others have demonstrated that the quadruplet decoding efficiency could be significantly enhanced by an extensive engineering of tRNAs bearing an extra nucleotide in their anticodon loops. In this work, we report the identification of tRNA mutants derived from directed evolution to efficiently decode a UAGA quadruplet codon in mammalian cells. Intriguingly, the trend of quadruplet codon decoding efficiency among the tested tRNA variants in mammalian cells was largely the same as that in E. coli. We subsequently demonstrate the utility of quadruplet codon decoding by the construction of the first HIV-1 mutant that lacks any in-frame amber nonsense codons and can be precisely activated by the decoding of a genomically embedded UAGA codon with an unnatural amino acid. Such conditionally activatable HIV-1 mutant can likely facilitate both fundamental investigations of HIV-1 as well as vaccine developments. The use of quadruplet codon, instead of an amber nonsense codon, to control HIV-1 replication has the advantage in that the correction of a frameshift caused by a quadruplet codon is much less likely than the reversion of an amber codon back into a sense codon in HIV-1. PMID- 29787235 TI - Novel Fast-Setting Mineral Trioxide Aggregate: Its Formulation, Chemical-Physical Properties, and Cytocompatibility. AB - One of the main drawbacks that limits the application of mineral trioxide aggregate (MTA) in dental field is its long setting time. Mineral trioxide aggregate with accelerated setting properties and excellent chemical-physical and biological properties is still required. In this study, an innovative mineral trioxide aggregate, which consists of calcium silicates, calcium aluminates, and zirconium oxide, was designed to obtain fast-setting property. The optimized formulation can achieve initial setting in 10 min and final setting in 15 min, which are much faster than commercial mineral trioxide aggregate. In addition, the optimized fast-setting MTA showed adequate radiopacity and good biocompatibility. The ion concentrations after storage in water for 1 day were 52.3 mg/L Ca, 67.7 mg/L Al, 48.8 mg/L Si, and 11.7 mg/L Mg. The hydration products of hardened cements were investigated by X-ray diffraction, scanning electron microscopy, and Fourier transform infrared, showing the accelerated setting time was due to the formation of honeycomb-like calcium silicate hydrate gel. The novel MTA could be a promising material for dental applications. PMID- 29787234 TI - Unfolding the Mysteries of Protein Metamorphosis. AB - Since the proposal of Anfinsen's thermodynamic hypothesis in 1963, our understanding of protein folding and dynamics has gained significant appreciation of its nuance and complexity. Intrinsically disordered proteins, chameleonic sequences, morpheeins, and metamorphic proteins have broadened the protein folding paradigm. Here, we discuss noncanonical protein folding patterns, with an emphasis on metamorphic proteins, and we review known metamorphic proteins that occur naturally and that have been engineered in the laboratory. Finally, we discuss research areas surrounding metamorphic proteins that are primed for future exploration, including evolution, drug discovery, and the quest for previously unrecognized metamorphs. As we enter an age where we are capable of complex bioinformatic searches and de novo protein design, we are primed to search for previously unrecognized metamorphic proteins and to design our own metamorphs to act as targeted, switchable drugs; biosensors; and more. PMID- 29787236 TI - Investigation of the Viability of Cells upon Co-Exposure to Gold and Iron Oxide Nanoparticles. AB - Cell lines were exposed either to mixtures of gold and iron oxide nanoparticles, or to a hybrid nanoparticle with gold and iron oxide domain. In the case of simultaneous exposure to gold and iron oxide nanoparticles, enhanced toxicity as compared to the exposure to only one type of nanoparticles was observed. An indication was found that, at equivalent concentrations, the hybrid nanoparticles may slightly reduce cell viability more strongly than mixtures of both nanoparticle types. The results suggest that composite nanomaterials, in which different materials are present in particle form, need to be analyzed carefully, as not only the concentration of the respective materials but also their arrangement may influence their toxicity. PMID- 29787237 TI - Compression-Induced Modification of Boron Nitride Layers: A Conductive Two Dimensional BN Compound. AB - The ability to create materials with improved properties upon transformation processes applied to conventional materials is the keystone of materials science. Here, hexagonal boron nitride (h-BN), a large-band-gap insulator, is transformed into a conductive two-dimensional (2D) material- bonitrol-that is stable at ambient conditions. The process, which requires compression of at least two h-BN layers and hydroxyl ions, is characterized via scanning probe microscopy experiments and ab initio calculations. This material and its creation mechanism represent an additional strategy for the transformation of known 2D materials into artificial advanced materials with exceptional properties. PMID- 29787238 TI - Antifibrotic Effect of Ketoprofen-Grafted Alginate Microcapsules in the Transplantation of Insulin Producing Cells. AB - The controlled release of small molecular modulators of the immune response from hydrogel microspheres (MS) used for cell immobilization is an attractive approach to reduce pericapsular fibrotic overgrowth (PFO) after transplantation. Ketoprofen is a well-known nonsteroidal anti-inflammatory drug involved in the early stage inflammation cascade. PEGylated derivatives of ketoprofen, presenting either ester or amide linkage to the drug, were synthesized and conjugated to the hydroxyl groups of sodium alginate (Na-alg). Functionalized cell-free and MIN6 cells containing MS were produced from the resulting modified alginates. In vitro quantification of ketoprofen release indicated regular and sustained drug delivery over 14 days, resulting from the hydrolytic cleavage of the ester bond. The release kinetics was enhanced over the initial 7 days by the presence of MIN6 cells, probably as a result of cell esterase activity. In the presence of amide bond, traces of ketoprofen were released over 14 days due to a much slower hydrolysis kinetics. Cell-free and MIN6 cells containing MS were transplanted in immune-competent mice, either in the peritoneal cavity or under the kidney capsule, with a follow-up period of 30 days. Comparison with nonmodified Ca-alg MS transplanted in the same conditions demonstrated a clear reduction in the severity of PFO for MS functionalized with ketoprofen. Quantification of collagen deposition on MIN6 cells containing MS transplanted under the kidney capsule revealed the significant effect of ketoprofen release to decrease fibrotic tissue formation. The impact was more pronounced when the drug was covalently conjugated by an ester linkage, allowing higher concentration of the anti-inflammatory compound to be delivered at the transplantation site. The functionality of microencapsulated MIN6 cells 30 days after transplantation was confirmed by detection of insulin positive cell content. PMID- 29787240 TI - Sulfonium Ion Condensation: The Burden Borne by SAM Synthetase. AB - S-Adenosylmethionine (SAM+) serves as the principal methylating agent in biological systems, but the thermodynamic basis of its reactivity does not seem to have been clearly established. Here, we show that methionine, methanol, and H+ combine to form S-methylmethionine (SMM+) with a temperature-independent equilibrium constant of 9.9 M-2. The corresponding group transfer potential of SMM+ (its free energy of hydrolysis at pH 7) is -8.2 kcal/mol. The "energy-rich" nature of sulfonium ions is related to the extreme acidity (p Ka -5.4) of the S protonated thioether produced by sulfonium hydrolysis, and the large negative free energy of deprotonation of that species in neutral solution (-16.7 kcal/mol). At pH 7, SAM synthetase requires the free energy released by cleavage of two bonds of ATP to reverse that process. PMID- 29787239 TI - Catalytic Bases and Stereocontrol in Lamiaceae Class II Diterpene Cyclases. AB - Plants from the widespread Lamiaceae family produce many labdane-related diterpenoids, a number of which serve medicinal roles, and whose biosynthesis is initiated by class II diterpene cyclases (DTCs). These enzymes utilize a general acid-base catalyzed cyclo-isomerization reaction to produce various stereoisomers of the eponymous labdaenyl carbocation intermediate, which can then undergo rearrangement and/or the addition of water prior to terminating deprotonation. Identification of the pair of residues that cooperatively serve as the catalytic base in the DTCs that produce ent-copalyl diphosphate (CPP) required for gibberellin phytohormone biosynthesis in all vascular plants has led to insight into the addition of water as well as rearrangement. Lamiaceae plants generally contain an additional DTC that produces the enantiomeric normal CPP, as well as others that yield hydroxylated products derived from the addition of water. Here the catalytic base in these DTCs was investigated. Notably, changing two adjacent residues that seem to serve as the catalytic base in the normal CPP synthase from Salvia miltiorrhiza (SmCPS) to the residues found in the closely related perigrinol diphosphate synthase from Marrubium vulgare (MvPPS), which produces a partially rearranged and hydroxylated product derived from the distinct syn stereoisomer of labdaenyl+, altered the product outcome in an unexpected fashion. Specifically, the relevant SmCPS:H315N/T316V double mutant produces terpentedienyl diphosphate, which is derived from complete substituent rearrangement of syn rather than normal labdaenyl+. Accordingly, alteration of the residues that normally serve as the catalytic base surprisingly can impact stereocontrol. PMID- 29787241 TI - Conjugated Polyelectrolytes as Efficient Hole Transport Layers in Perovskite Light-Emitting Diodes. AB - Perovskite-based optoelectronic devices have been rapidly developing in the past 5 years. Since the first report, the external quantum efficiency (EQE) of perovskite light-emitting diodes (PeLEDs) has increased rapidly through the control of morphology and structure from 0.1% to more than 11%. Here, we report the use of various conjugated polyelectrolytes (CPEs) as the hole injection layer in PeLEDs. In particular, we find that poly[2,6-(4,4-bis-potassium butanylsulfonate)-4 H-cyclopenta-[2,1- b;3,4- b']-dithiophene)] (PCPDT-K) transfers holes effectively, blocks electron transport from the perovskite to the underlying ITO layer, and reduces luminescence quenching at the perovskite/PCPDT K interface. Our optimized PeLEDs with PCPDT-K show enhanced EQE by a factor of approximately 4 compared to control PeLEDs with PEDOT:PSS, reaching EQE values of 5.66%, and exhibit improved device stability. PMID- 29787242 TI - Membrane Topology of Trafficking Regulator of GLUT4 1 (TRARG1). AB - Trafficking regulator of GLUT4 1 (TRARG1) was recently identified to localize to glucose transporter type 4 (GLUT4) storage vesicles (GSVs) and to positively regulate GLUT4 trafficking. Our knowledge of TRARG1 structure and membrane topology is limited to predictive models, hampering efforts to further our mechanistic understanding of how it carries out its functions. Here, we use a combination of bioinformatics prediction tools and biochemical assays to define the membrane topology of the 173-amino acid mouse TRARG1. These analyses revealed that, contrary to the consensus prediction, the N-terminus is cytosolic and that a short segment at the C-terminus resides in the luminal/extracellular space. Based on our biochemical analyses including membrane association and antibody accessibility assays, we conclude that TRARG1 has one transmembrane domain (TMD) (145-172) and a re-entrant loop between residues 101 and 127. PMID- 29787243 TI - Benchmark Analysis of Native and Artificial NAD+-Dependent Enzymes Generated by a Sequence-Based Design Method with or without Phylogenetic Data. AB - The expansion of protein sequence databases has enabled us to design artificial proteins by sequence-based design methods, such as full-consensus design (FCD) and ancestral-sequence reconstruction (ASR). Artificial proteins with enhanced activity levels compared with native ones can potentially be generated by such methods, but successful design is rare because preparing a sequence library by curating the database and selecting a method is difficult. Utilizing a curated library prepared by reducing conservation energies, we successfully designed two artificial l-threonine 3-dehydrogenases (SDR-TDH) with higher activity levels than native SDR-TDH, FcTDH-N1, and AncTDH, using FCD and ASR, respectively. The artificial SDR-TDHs had excellent thermal stability and NAD+ recognition compared to native SDR-TDH from Cupriavidus necator (CnTDH); the melting temperatures of FcTDH-N1 and AncTDH were about 10 and 5 degrees C higher than that of CnTDH, respectively, and the dissociation constants toward NAD+ of FcTDH-N1 and AncTDH were 2- and 7-fold lower than that of CnTDH, respectively. Enzymatic efficiency of the artificial SDR-TDHs were comparable to that of CnTDH. Crystal structures of FcTDH-N1 and AncTDH were determined at 2.8 and 2.1 A resolution, respectively. Structural and MD simulation analysis of the SDR-TDHs indicated that only the flexibility at specific regions was changed, suggesting that multiple mutations introduced in the artificial SDR-TDHs altered their flexibility and thereby affected their enzymatic properties. Benchmark analysis of the SDR-TDHs indicated that both FCD and ASR can generate highly functional proteins if a curated library is prepared appropriately. PMID- 29787245 TI - Structure and Dynamics of a Graphene Melt. AB - We explore the structural and dynamic properties of bulk materials composed of graphene nanosheets using coarse-grained molecular dynamics simulations. Remarkably, our results show clear evidence that bulk graphene materials exhibit a fluid-like behavior similar to linear polymer melts at elevated temperatures and that these materials transform into a glassy-like "foam" state at temperatures below the glass-transition temperature ( Tg) of these materials. Distinct from an isolated graphene sheet, which exhibits a relatively flat shape with fluctuations, we find that graphene sheets in a melt state structurally adopt more "crumpled" configurations and correspondingly smaller sizes, as normally found for ordinary polymers in the melt. Upon approaching the glass transition, these two-dimensional polymeric materials exhibit a dramatic slowing down of their dynamics that is likewise similar to ordinary linear polymer glass forming liquids. Bulk graphene materials in their glassy foam state have an exceptionally large free-volume and high thermal stability due to their high Tg (~ 1600 K) as compared to conventional polymer materials. Our findings show that graphene melts have interesting lubricating and "plastic" flow properties at elevated temperatures, and suggest that graphene foams are highly promising as high surface filtration materials and fire suppression additives for improving the thermal conductivities and mechanical reinforcement of polymer materials. PMID- 29787244 TI - High-Performance Cells Containing Lithium Metal Anodes, LiNi0.6Co0.2Mn0.2O2 (NCM 622) Cathodes, and Fluoroethylene Carbonate-Based Electrolyte Solution with Practical Loading. AB - We report on the highly stable lithium metal|LiNi0.6Co0.2Mn0.2O2 (NCM 622) cells with practical electrodes' loading of 3.3 mA h g-1, which can undergo many hundreds of stable cycles, demonstrating high rate capability. A key issue was the use of fluoroethylene carbonate (FEC)-based electrolyte solutions (1 M LiPF6 in FEC/dimethyl carbonate). Li|NCM 622 cells can be cycled at 1.5 mA cm-2 for more than 600 cycles, whereas symmetric Li|Li cells demonstrate stable performance for more than 1000 cycles even at higher areal capacity and current density. We attribute the excellent performance of both Li|NCM and Li|Li cells to the formation of a stable and efficient solid electrolyte interphase (SEI) on the surface of the Li metal electrodes cycled in FEC-based electrolyte solutions. The composition of the SEI on the Li and the NCM electrodes is analyzed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. A drastic capacity fading of Li|NCM cells is observed, followed by spontaneous capacity recovery during prolonged cycling. This phenomenon depends on the current density and the amount of the electrolyte solution and relates to kinetic limitations because of SEI formation on the Li anodes in the FEC-based electrolyte solution. PMID- 29787246 TI - Investigation of Solvent Hydron Exchange in the Reaction Catalyzed by the Antibiotic Resistance Protein Cfr. AB - Cfr is a radical S-adenosylmethionine (RS) methylase that appends methyl groups to C8 and C2 of adenosine 2503 in 23S rRNA. Methylation of C8 confers resistance to several classes of antibiotics that bind in or near the peptidyltransferase center of the bacterial ribosome, including the synthetic antibiotic linezolid. The Cfr reaction requires the action of five conserved cysteines, three of which ligate a required [4Fe-4S] cluster cofactor. The two remaining cysteines play a more intricate role in the reaction; one (Cys338) becomes transiently methylated during catalysis. The function of the second (Cys105) has not been rigorously established; however, in the related RlmN reaction, it (Cys118) initiates resolution of a key protein-nucleic acid cross-linked intermediate by abstracting the proton from the carbon center (C2) undergoing methylation. We previously proposed that, unlike RlmN, Cfr would utilize a polyprotic base during resolution of the protein-nucleic acid cross-linked intermediate during C8 methylation and, like RlmN, use a monoprotic base during C2 methylation. We based this proposal on the fact that solvent hydrons could exchange into the product during C8 methylation, but not during C2 methylation. Herein, we show that Cys105 of Cfr has a function similar to that of Cys118 of RlmN while methylating C8 of A2503 and provide evidence for one molecule of water that is in close contact with it, which provides the exchangeable protons during catalysis. PMID- 29787247 TI - Enhanced Photogeneration of Reactive Oxygen Species and Targeted Photothermal Therapy of C6 Glioma Brain Cancer Cells by Folate-Conjugated Gold-Photoactive Polymer Nanoparticles. AB - Tumor-selective photodynamic therapy is a successful method for ablation of malignant and cancerous cells. Herein, we introduce the design and preparation of functionalized acrylic copolymer nanoparticles with spiropyran (SP) and imidazole groups through a facile semicontinuous emulsion polymerization. Then, Au3+ ions were immobilized and reduced on their surface to obtain photoresponsive gold decorated polymer nanoparticles (PGPNPs). The prepared PGPNPs were surface modified with folic acid as a site-specific tumor cell targeting agent and improve intracellular uptake via endocytosis. Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy analyses, UV-vis spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy images were employed to characterize their spectral and morphological properties. Fluorescence microscopy images and inductively coupled plasma analysis demonstrated the cell line labeling capability and improved targeting efficiency of folate-conjugated PGPNPs (FA-PGPNPs) toward rat brain cancer cells (C6 glioma) with 71.8% cell uptake in comparison with 28.8% for the nonconjugated ones. Nonpolar SP groups are converted to zwitterionic merocyanine isomers under UV irradiation at 365 nm and their conjugation with Au nanoparticles exhibited enhanced photogeneration of reactive oxygen species (ROS). These were confirmed by intracellular ROS analysis and cytotoxicity evaluation on malignant C6 glioma cells. Owing to the strong surface plasmon resonance absorption of gold nanoparticles, FA-PGPNPs provided elevated local photothermal efficiency under near-IR irradiation at 808 nm. The prepared multifunctional FA-PGPNPs with a comprehensive integration of prospective materials introduced promising nanoprobes with targeting ability, enhanced tumor photodynamic therapy, cell tracking, and photothermal therapy. PMID- 29787248 TI - Efficient n-Doping and Hole Blocking in Single-Walled Carbon Nanotube Transistors with 1,2,4,5-Tetrakis(tetramethylguanidino)ben-zene. AB - Efficient, stable, and solution-based n-doping of semiconducting single-walled carbon nanotubes (SWCNTs) is highly desired for complementary circuits but remains a significant challenge. Here, we present 1,2,4,5 tetrakis(tetramethylguanidino)benzene (ttmgb) as a strong two-electron donor that enables the fabrication of purely n-type SWCNT field-effect transistors (FETs). We apply ttmgb to networks of monochiral, semiconducting (6,5) SWCNTs that show intrinsic ambipolar behavior in bottom-contact/top-gate FETs and obtain unipolar n-type transport with 3-5-fold enhancement of electron mobilities (approximately 10 cm2 V-1 s-1), while completely suppressing hole currents, even at high drain voltages. These n-type FETs show excellent on/off current ratios of up to 108, steep subthreshold swings (80-100 mV/dec), and almost no hysteresis. Their excellent device characteristics stem from the reduction of the work function of the gold electrodes via contact doping, blocking of hole injection by ttmgb2+ on the electrode surface, and removal of residual water from the SWCNT network by ttmgb protonation. The ttmgb-treated SWCNT FETs also display excellent environmental stability under bias stress in ambient conditions. Complementary inverters based on n- and p-doped SWCNT FETs exhibit rail-to-rail operation with high gain and low power dissipation. The simple and stable ttmgb molecule thus serves as an example for the larger class of guanidino-functionalized aromatic compounds as promising electron donors for high-performance thin film electronics. PMID- 29787249 TI - Structure-Function Relationships in the Oligomeric NADPH-Dependent Assimilatory Sulfite Reductase. AB - The central step in the assimilation of sulfur is a six-electron reduction of sulfite to sulfide, catalyzed by the oxidoreductase NADPH-dependent assimilatory sulfite reductase (SiR). SiR is composed of two subunits. One is a multidomain flavin binding reductase (SiRFP) and the other an iron-containing oxidase (SiRHP). Both enzymes are primarily globular, as expected from their functions as redox enzymes. Consequently, we know a fair amount about their structures but not how they assemble. Curiously, both structures have conspicuous regions that are structurally undefined, leaving questions about their functions and raising the possibility that they are critical in forming the larger complex. Here, we used ultraviolet-visible and circular dichroism spectroscopy, isothermal titration calorimetry, proteolytic sensitivity tests, electrospray ionization mass spectrometry, and activity assays to explore the effect of altering specific amino acids in SiRFP on their function in the holoenzyme complex. Additionally, we used computational analysis to predict the propensity for intrinsic disorder within both subunits and found that SiRHP's N-terminus is predicted to have properties associated with intrinsic disorder. Both proteins also contained internal regions with properties indicative of intrinsic disorder. We showed that SiRHP's N-terminal disordered region is critical for complex formation. Together with our analysis of SiRFP amino acid variants, we show how molecular interactions outside the core of each SiR globular enzyme drive complex assembly of this prototypical oxidoreductase. PMID- 29787250 TI - Pharmacokinetics in Plants: Carbamazepine and Its Interactions with Lamotrigine. AB - Carbamazepine and lamotrigine prescribed antiepileptic drugs are highly persistent in the environment and were detected in crops irrigated with reclaimed wastewater. This study reports pharmacokinetics of the two drugs and their metabolites in cucumber plants under hydroponic culture, testing their uptake, translocation, and transformation over 96 h in single and bisolute systems at varying pH. Ruling out root adsorption and transformations in the nutrient solution, we demonstrate that carbamazepine root uptake is largely affected by the concentration gradient across the membrane. Unlike carbamazepine, lamotrigine is adsorbed to the root and undergoes ion trapping in root cells thus its translocation to the shoots is limited. On the basis of that, carbamazepine uptake was not affected by the presence of lamotrigine, while lamotrigine uptake was enhanced in the presence of carbamazepine. Transformation of carbamazepine in the roots was slightly reduced in the presence of lamotrigine. Carbamazepine metabolism was far more pronounced in the shoots than in the roots, indicating that most of the metabolism occurs in the leaves, probably due to higher concentration and longer residence time. This study indicates that the uptake of small nonionic pharmaceuticals is passive and governed by diffusion across the root membrane. PMID- 29787251 TI - Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates. AB - Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp3)-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1 degrees and 2 degrees aliphatic amines can be arylated selectively at their gamma-C-H positions. In addition to potentially serving as a directing group, CO2 has also been demonstrated to curtail the oxidation of sensitive amine substrates. PMID- 29787253 TI - Dissolved Organophosphate Esters and Polybrominated Diphenyl Ethers in Remote Marine Environments: Arctic Surface Water Distributions and Net Transport through Fram Strait. AB - Organophosphate esters (OPEs) have been found in remote environments at unexpectedly high concentrations, but very few measurements of OPE concentrations in seawater are available, and none are available in subsurface seawater. In this study, passive polyethylene samplers (PEs) deployed on deep-water moorings in the Fram Strait and in surface waters of Canadian Arctic lakes and coastal sites were analyzed for a suite of common OPEs. Total OPEs ( ?11OPE) at deep-water sites were dominated by chlorinated OPEs, and ranged from 6.3 to 440 pg/L. Concentrations were similar in eastern and western Fram Strait. Chlorinated OPEs were also dominant in Canadian Arctic surface waters (mean concentration ranged from < DL to 4400 pg/L), while nonhalogenated alkyl/aryl-substituted OPEs remained low (1.3-55 pg/L), possibly due to the greater long-range transport potential of chlorinated OPEs. Polybrominated diphenyl ethers (PBDEs) were found at much lower concentrations than OPEs (= lambda/2 (lambda is the reorganization energy). With increasing temperature, the polaron becomes more localized and the mobility exhibits a "band-like" power law decay due to increased site energy and electronic coupling fluctuations (local and nonlocal electron-phonon coupling). Thus, reducing both types of electron phonon coupling while retaining high mean electronic couplings should be part of the strategy toward discovery of new organics with high room-temperature mobilities. PMID- 29787276 TI - Effects of Frequency Dependence of the External Quantum Efficiency of Perovskite Solar Cells. AB - Perovskite solar cells are known to show very long response time scales, on the order of milliseconds to seconds. This generates considerable doubt over the validity of the measured external quantum efficiency (EQE) and consequently the estimation of the short-circuit current density. We observe a variation as high as 10% in the values of the EQE of perovskite solar cells for different optical chopper frequencies between 10 and 500 Hz, indicating a need to establish well defined protocols of EQE measurement. We also corroborate these values and obtain new insights regarding the working mechanisms of perovskite solar cells from intensity-modulated photocurrent spectroscopy measurements, identifying the evolution of the EQE over a range of frequencies, displaying a singular reduction at very low frequencies. This reduction in EQE is ascribed to additional resistive contributions hindering charge extraction in the perovskite solar cell at short-circuit conditions, which are delayed because of the concomitant large low-frequency capacitance. PMID- 29787278 TI - Naphthalimide-Based DNA-Coupled Hybrid Assembly for Sensing Dipicolinic Acid: A Biomarker for Bacillus anthracis Spores. AB - We have designed and synthesized a novel, water-soluble naphthalimide-histidine receptor (1) with excellent fluorescent properties. Functioning of the synthesized receptor was performed through developing their DNA-receptor hybrid assembly (DRHA), which has shown significant changes in the emission profile upon interactions with dipicolinic acid (DPA), a biomarker for Bacillus anthracis spores. DRHA showed fluorescence enhancement upon binding with DPA with the characteristic of internal charge transfer. It is notable that this assembly exhibited a significant limit of detection (12 nM) toward DPA. The mechanism of sensing was fully defined using ethidium bromide (EtBr) interaction studies as well as Fourier transform infrared spectroscopic analysis, which describes the binding mode of DRHA with DPA. This assembly selectively interacts with DPA over other anions, common cellular cations, and aromatic acids in aqueous media. PMID- 29787277 TI - Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer. AB - Tamoxifen administration enhanced overall disease-free survival and diminished mortality rates in cancer patients. However, patients with breast cancer often fail to respond for tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2, and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show chemosensitize tamoxifen-resistant cancers. Based on chemotoxicity issues, researchers are actively investigating alternative therapeutic strategies. In the current study, we fabricate a mesoporous silica gold cluster nanodrug delivery system that displays exceptional tumor-targeting capability, thus promoting accretion of drug indices at the tumor site. We employ dual drugs, ZD6474, and epigallocatechin gallate (EGCG) that inhibit EGFR2, VEGFR2, and Akt signaling pathways since changes in these signaling pathways confer tamoxifen resistance in MCF 7 and T-47D cells. Mesoporous silica gold cluster nanodrug delivery of ZD6474 and EGCG sensitize tamoxifen-resistant cells to apoptosis. Western and immune-histochemical analyses confirmed the apoptotic inducing properties of the nanoformulation. Overall, results with these silica gold nanoclusters suggest that they may be a potent nanoformulation against chemoresistant cancers. PMID- 29787279 TI - Multinuclear Detection of Nuclear Spin Optical Rotation at Low Field. AB - We describe the multinuclear detection of nuclear spin optical rotation (NSOR), an effect dependent on the hyperfine interaction between nuclear spins and electrons. Signals of 1H and 19F are discriminated by frequency in a single spectrum acquired at sub-millitesla field. The simultaneously acquired optical signal along with the nuclear magnetic resonance signal allows the calculation of the relative magnitude of the NSOR constants corresponding to different nuclei within the sample molecules. This is illustrated by a larger NSOR signal measured at the 19F frequency despite a smaller corresponding spin concentration. Second, it is shown that heteronuclear J-coupling is observable in the NSOR signal, which can be used to retrieve chemical information. Multinuclear frequency and J resolution can localize optical signals in the molecule. Properties of electronic states at multiple sites in a molecule may therefore ultimately be determined by frequency-resolved NSOR spectroscopy at low field. PMID- 29787280 TI - Transition-Metal-Free Regioselective Cross-Coupling: Controlled Synthesis of Mono or Dithiolation Indolizines. AB - An efficient transition-metal-free regioselective C-H/S-H cross-coupling of indolizines with thiols has been developed for the first time to describe a workable route to indolizine thioethers. This finding provides a new method and more straightforward pathway for controllable synthesis of mono- or dithiolation indolizines that are otherwise difficult to obtain by the literature methods. The reaction exhibits good functional group tolerance and high efficiency and affords the products in good to excellent yields. PMID- 29787282 TI - Regulating the Uptake of Viral Nanoparticles in Macrophage and Cancer Cells via a pH Switch. AB - Controlling the uptake of nanomaterials into phagocytes is a challenging problem. We describe an approach to inhibit the cellular uptake by macrophages and HeLa cells of nanoparticles derived from bacteriophage Qbeta by conjugating negatively charged terminal hexanoic acid moieties onto its surface. Additionally, we show hydrazone linkers can be installed between the surface of Qbeta and the terminal hexanoic acid moieties, resulting in a pH-responsive conjugate that, in acidic conditions, can release the terminal hexanoic acid moiety and allow for the uptake of the Qbeta nanoparticle. The installation of the "pH switch" did not change the structure-function properties of the hexanoic acid moiety and the uptake of the Qbeta conjugates by macrophages. PMID- 29787281 TI - Palladium-Catalyzed Ring-Forming Alkene Aminoaroylation of Unsaturated Hydrazones and Sulfonamides. AB - The first example of a Pd(OAc)2-catalyzed ring-forming alkene aminoaroylation of unsaturated hydrazones and sulfonamides is described. This protocol features the use of diaryliodonium salts as both oxidants and aryl sources, thus enabling mild reaction conditions, good chemoselectivity, a broad substrate scope, and high functional group tolerance. A wide range of synthetically and biologically important functionalized dihydropyrazoles and isoxazolidines have been obtained in good yields. PMID- 29787284 TI - Selective Synthesis of Aryl Nitriles and 3-Imino-1-oxoisoindolines via Nickel Promoted C(sp2)-H Cyanations. AB - An efficient nickel-promoted selective monocyanation of benzamides with TMSCN via 8-aminoquinoline directed ortho C-H activation has been developed. Varieties of functionalized ortho-cyanated (hetero)aryl nitriles can be selectively synthesized in moderate to good yields. These cyanation products can be easily transformed into various 3-imino-1-oxoisoindolines in a one-pot procedure. The mild reaction conditions, use of cheap and commercially available reagents, wide functional group tolerance, and operational convenience make this protocol practical to the synthetic community. PMID- 29787286 TI - Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels-Alder Strategy. AB - A concise total synthesis of the neoclerodane diterpene salvinorin A from 3 furaldehyde is reported using two highly diastereoselective intramolecular Diels Alder reactions (IMDA) as the key transformations. PMID- 29787283 TI - 86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model. AB - Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, 86Y and 90Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti CD105 antibody, TRC105. Serial positron emission tomography imaging with 86Y-DTPA TRC105 demonstrated high uptake in 4T1 tumors, peaking at 9.6 +/- 0.3%ID/g, verified through ex vivo studies. Additionally, promising results were obtained in therapeutic studies with 90Y-DTPA-TRC105, wherein significantly ( p < 0.05) decreased tumor volumes were observed for the targeted treatment group over all control groups near the end of the study. Dosimetric extrapolation and tissue histological analysis corroborated trends found in vivo. Overall, this study demonstrated the potential of the pair 86/90Y for theranostics, enabling personalized treatments for cancer. PMID- 29787285 TI - Metasurface Mirrors for External Control of Mie Resonances. AB - The ability to control and structurally tune the optical resonances of semiconductor nanostructures has far-reaching implications for a wide range of optical applications, including photodetectors, (bio)sensors, and photovoltaics. Such control is commonly obtained by tailoring the nanostructure's geometry, material, or dielectric environment. Here, we combine insights from the field of coherent optics and metasurface mirrors to effectively turn Mie resonances on and off with high spatial control and in a polarization-dependent fashion. We illustrate this in an integrated device by manipulating the photocurrent spectra of a single-nanowire photodetector placed on a metasurface mirror. This approach can be generalized to control spectral, angle-dependent, absorption, and scattering properties of semiconductor nanostructures with an engineered metasurface and without a need to alter their geometric or materials properties. PMID- 29787287 TI - Associations between Parasympathetic Activity in the Month after Birth and Wheeze at Age 2-3 Years. PMID- 29787289 TI - Trends of LSD1 inhibitors in viral infections. PMID- 29787290 TI - Amalgamation of polyphenols and probiotics induce health promotion. AB - The residing microbiome with its vast repertoire of genes provide distinctive properties to the host by which they can degrade and utilise nutrients that otherwise pass the gastro-intestinal tract unchanged. The polyphenols in our diet have selective growth promoting effects which is of utmost importance as the state of good health has been linked to dominance of particular microbial genera. The polyphenols in native form might more skilfully exert anti-oxidative and anti inflammatory properties but in a living system it is the microbial derivatives of polyphenol that play a key role in determining health outcome. This two way interaction has invoked great interest among researchers who have commenced several clinical surveys and numerous studies in in-vitro, simulated environment and living systems to find out in detail about the biomolecules involved in such interaction along with their subsequent physiological benefits. In this review, we have thoroughly discussed these studies to develop a fair idea on how the amalgamation of probiotics and polyphenol has an immense potential as an adjuvant therapeutic for disease prevention as well as treatment. PMID- 29787291 TI - Extrusion processing of raw food materials and by-products: A review. AB - Extrusion technology has rapidly transformed the food industry with its numerous advantages over other processing methods. It offers a platform for processing different products from various food groups by modifying minor or major ingredients and processing conditions. Although cereals occupy a large portion of the extruded foods market, several other types of raw materials have been used. Extrusion processing of various food groups, including cereals and pseudo cereals, roots and tubers, pulses and oilseeds, fruits and vegetables, and animal products, as well as structural and nutritional changes in these food matrices are reviewed. Value addition by extrusion to food processing wastes and by products from fruits and vegetables, dairy, meat and seafood, cereals and residues from starch, syrup and alcohol production, and oilseed processing are also discussed. Extrusion presents an economical technology for incorporating food processing residues and by-products back into the food stream. In contemporary scenarios, rising demand for extruded products with functional ingredients, attributed to evolving lifestyles and preferences, have led to innovations in the form, texture, color and content of extruded products. Information presented in this review would be of importance to processors and researchers as they seek to enhance nutritional quality and delivery of extruded products. PMID- 29787292 TI - Signature microRNA expression profile is associated with spontaneous hypertension in African green monkey. AB - Chlorocebus aethiops sabaeus, the African Green monkey (AGM), has been proved to exhibit renal vascular remodeling and spontaneous hypertension. However, little is known about the roles of microRNAs (miRNAs) in this process.Using small RNA deep sequencing, we compared the plasma miRNA expression patterns between hypertensive (HT) AGMs and normotensive (NT) AGMs. Expression of miRNAs (miR-122, miR-339, miR-296-5p) was validated independently in plasma samples from 10 HT AGMs and 10 NT AGMs (fold changes are 2.0, 1.6, 2.7 respectively; all P< 0.001). Potential BP (blood pressure)-regulating mRNA targets were predicted by TargetScan and confirmed in the Vero cells. We report for the first time a circulating miRNA profile for AGM. miRNAs, such as miR-122, miR-339, miR-296-5p, may be involved in renal pathologies and spontaneous hypertension of AGM. PMID- 29787294 TI - Quantifying the Strength of General Factors in Psychopathology: A Comparison of CFA with Maximum Likelihood Estimation, BSEM, and ESEM/EFA Bifactor Approaches. AB - Whether or not importance should be placed on an all-encompassing general factor of psychopathology (or p factor) in classifying, researching, diagnosing, and treating psychiatric disorders depends (among other issues) on the extent to which comorbidity is symptom-general rather than staying largely within the confines of narrower transdiagnostic factors such as internalizing and externalizing. In this study, we compared three methods of estimating p factor strength. We compared omega hierarchical and explained common variance calculated from confirmatory factor analysis (CFA) bifactor models with maximum likelihood (ML) estimation, from exploratory structural equation modeling/exploratory factor analysis models with a bifactor rotation, and from Bayesian structural equation modeling (BSEM) bifactor models. Our simulation results suggested that BSEM with small variance priors on secondary loadings might be the preferred option. However, CFA with ML also performed well provided secondary loadings were modeled. We provide two empirical examples of applying the three methodologies using a normative sample of youth (z-proso, n = 1,286) and a university counseling sample (n = 359). PMID- 29787288 TI - A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE). AB - RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the DeltaEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a DeltaFEV1 greater than or equal to 15% (P < 0.001). DeltaEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant DeltaEBV-SoC were also observed in hyperinflation (residual volume, 522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392). PMID- 29787293 TI - Compulsive sexual behavior: A twelve-step therapeutic approach. AB - Background and aims Sexuality is natural to human life and inseparable from it, yet some individuals develop compulsive sexual behavior (CSB). Many individuals with CSB seek treatment in free self-support groups based on the twelve-step program. This program was extensively studied in substance abuse disorders (e.g., Alcoholics Anonymous), but little is known about its efficiency in CSB. Methods We "assesed" questionnaire data on sociodemographical-, psychological-, and recovery-related factors from 97 male participants of Sexaholics Anonymous (SA) programs in Israel. Results Our results indicated that advancement in the SA program, measured as a current step of the program, is significantly related to lower levels of sexual-related overall sense of helplessness, avoidant help seeking, self-control, overall CSB, and sexual suppression. It is also related to the higher well-being. Discussion This is the first study to examine psychological factors of CSB recovery process in twelve-step groups, and future research is needed to replicate our results within a longitudinal study. PMID- 29787295 TI - Alertness and psychomotor performance levels of marine pilots on an irregular work roster. AB - Fatigue is recognized as an important safety concern in the transportation industry. In this study, our goal was to investigate how circadian and sleep-wake dependent factors influence St-Lawrence River pilots' sleep-wake cycle, alertness and psychomotor performance levels at work. A total of 18 male St-Lawrence River ship pilots were recruited to a 16-21-day field study. Pilots' chronotype, sleepiness and insomnia levels were documented using standardized questionnaires. Their sleep-wake cycle was documented by a sleep-wake log and wrist-worn activity monitoring. Subjective alertness and objective psychomotor performances were assessed ~5*/day for each work and rest day. Ship transits were distributed throughout the 24-h day and lasted on average (+/- SEM) 5.93 +/- 0.67 h. Main sleep periods occurred mainly at night, and objectively lasted 6.04 +/- 1.02 h before work days. When going to bed at the end of work days, pilots subjectively reported sleeping 7.64 +/- 1.64 h in the prior 24 h. Significant diurnal and wake dependent effects were observed for subjective alertness and objective psychomotor performance, with minimum levels occurring between 09:00 and 10:00. Thus, despite their irregular work schedule, ship pilots presented, as a group, a diurnal variation of alertness and psychomotor performance indicative of a day oriented circadian system. Important inter-individual differences were observed on psychomotor performance mesor and phase. In individuals, earlier phases in psychomotor performance were correlated with earlier chronotype. This study indicates that both circadian and homeostatic processes modulate alertness and psychomotor performance levels with worst levels reached when long shifts ended in the morning. This work has potential applications as it indicates fatigue countermeasures considering both processes are scientifically based. PMID- 29787297 TI - Design, synthesis, anticancer screening, docking studies and in silico ADME prediction of some beta-carboline derivatives. AB - BACKGROUND: Medicinal interest has focused on beta-carbolines as anticancer agents. METHODOLOGY/RESULTS: Several beta-carbolines were designed, synthesized and evaluated for their cytotoxic activity against MCF-7 and A-549 cancer cell lines using MTT assay. Compounds 13a, 13c, 13d and 20a were the most promising showing high selectivity indices. Compounds 13c and 20a showed potent inhibition of topoisomerase (topo-I) and kinesin spindle protein (KSP/Eg5 ATPase) which was confirmed by their docking results into the active site of both enzymes. In silico physicochemical calculations predicted that compounds 13a, 13d and 20a obeyed Lipinski's rule of five. CONCLUSION: Compounds 13c and 20a are multitarget anticancer leads that act as potent inhibitors for both topo-I and/or KSP ATPase. PMID- 29787298 TI - Uses and Misuses of Ted Kaczynski's MMPI. AB - Although case studies can be a helpful didactic aid when teaching personality assessment and illustrating use of a test, they can, of course, not be used as "evidence" that a test "works" or does not work. This article, however, reviews and discusses the far more problematic uses instantiated in a case study of Ted Kaczynski's Minnesota Multiphasic Personality Inventory (MMPI). A series of errors of omission and commission are identified in Butcher, Hass, Greene, and Nelson's ( 2015 ) effort to criticize the MMPI-2-RF. These include not disclosing that Butcher's interpretive Minnesota Report for Forensic Settings indicates that the protocol is invalid, not including most of the MMPI-2 and MMPI-2-RF scores that contradict the authors' assertions, and mischaracterizing the MMPI-2-RF findings. Proper use of a case study is then illustrated by a discussion of diagnostic considerations indicated by the MMPI-2-RF findings. PMID- 29787296 TI - Short Tandem Repeat (STR) Profiles of Commonly Used Human Ocular Surface Cell Lines. AB - PURPOSE: The purpose of this study is to establish the short tandem repeat (STR) profiles of several human cell lines commonly used in ocular surface research. MATERIALS AND METHODS: Independently DNA was extracted from multiple passages of three human corneal epithelial cell lines, two human conjunctival epithelial cell lines and one meibomian gland cell line, from different laboratories actively involved in ocular surface research. The samples were then subjected to STR analysis on a fee-for-service basis in an academic setting and the data compared against that in available databases. RESULTS: The STR profiles for the human corneal epithelial cells were different among the three cell lines studied and for each line the profiles were identical across the samples provided by three laboratories. Profiles for the human conjunctival epithelial cells were different among the two cell lines studied. Profiles for the meibomian gland cell line were identical across the samples provided by three laboratories. No samples were contaminated by elements of other cell lines such as HeLa. CONCLUSIONS: This comprehensive study provides verification of STR profiles for commonly used human ocular surface cell lines that can now be used as a reference by others in the field to authenticate the cell lines in use in their own laboratories. PMID- 29787299 TI - The influences of thermal processing on phytochemicals and possible routes to the discovery of new phytochemical conjugates. AB - In our diets, many of the consumed foods are subjected to various forms of heating and thermal processing. Besides enhancing the taste, texture, and aroma of the foods, heating helps to sterilize and facilitate food storage. On the other hand, heating and thermal processing are frequently reported during the preparation of various traditional herbal medicines. In this review, we intend to highlight works by various research groups which reported on changes in phytochemicals and bioactivities, following thermal processing of selected plant derived foods and herbal medicines. Relevant cases from plant-derived foods (garlic, coffee, cocoa, barley) and traditional herbal medicines (Panax ginseng, Polygonum multiforum, Aconitum carmichaelii Debeaux, Angelica sinensis Radix) will be presented in this review. Additionally, related works using pure phytochemical compounds will also be highlighted. In some of these cases, the amazing formation of new compounds were being reported. Maillard reaction could be concluded as the predominant pathway leading to the formation of new conjugates, along with other possibilities being suggested (degradation, transglycosylation, deglycosylation and dehydration). With collective efforts from all researchers, it is hoped that more details will be revealed and lead to the possible discovery of new, heat-mediated phytochemical conjugates. PMID- 29787300 TI - Recent progress in the discovery and development of DNA gyrase B inhibitors. AB - New antibacterials that modulate less explored targets are needed to fight the emerging bacterial resistance. DNA gyrase and topoisomerase IV are attractive targets in this search. These are both type II topoisomerases that can cleave both DNA strands, and can thus alter DNA topology during replication or similar processes. Currently, there are no ATP-competitive inhibitors of these two enzymes on the market, as the only aminocoumarin representative, novobiocin, was withdrawn due to safety concerns. The search for novel ATP-competitive inhibitors is a focus of ongoing industrial and academical research. This review summarizes the recent efforts in the design, synthesis and evaluation of GyrB/ParE inhibitors. The various approaches to achieve improved antibacterial activities are described, with particular reference to Gram-negative bacteria. PMID- 29787301 TI - Innovative Surgical Treatment of Severe Cherubism. AB - BACKGROUND: Cherubism is an autosomal dominant syndrome characterized by excessive bilateral maxillomandibular bony degeneration and fibrous tissue hyperplasia. Conservative management is the preferred treatment as cherubism has a self-limiting course. Functional or emotional disturbances may, however, demand surgical intervention. We report a patient who underwent surgical intervention. Method/Description: He had significant enlargement of lower cheeks and bilateral lower lid scleral show. On computed tomography of the face, the patient had significant fibrous tissue involving bilateral maxilla and mandible. The mandibular tumor was excised. Given normal inferior border, bilateral sagittal split osteotomy was performed to infracture and inset the outer cortex. During the procedure, patient required blood transfusion intraoperatively, so the maxillary portion of the procedure was delayed until 6 months later. For the maxilla, bilateral transconjunctival approach was used to resect parts of the orbital floors that were concave, resulting in 1 * 2 cm defects bilaterally which were reconstructed using resorbable plates. Then the anterior maxillary tumor was excised. RESULTS: The patient and his parents were satisfied with his appearance after surgery. The patient was noted to have improvement in contour and decreased scleral show. He has most recently followed up 15 months after the initial surgery. There were no long-term complications. CONCLUSIONS: Severity of cherubism influences the type of surgical intervention. The present case is innovative because this is the first reported case of recontouring orbital floors with resorbable plates and infracturing of the mandible using sagittal split osteotomies for surgical treatment of cherubism. PMID- 29787302 TI - Orthodontic-Surgical Approach for Treating Skeletal Class III Malocclusion With Severe Maxillary Deficiency in Isolated Cleft Palate. AB - Orthodontic treatment in patients with orofacial cleft such as cleft lip and palate or isolated cleft palate is challenging, especially when the patients exhibit severe maxillary growth retardation. To correct this deficiency, maxillary expansion and protraction can be performed in the first phase of orthodontic treatment. However, in some cases, the malocclusion cannot be corrected by these procedures, and thus, skeletal discrepancy remains when the patients are adolescents. These remaining problems occasionally require various orthognathic treatments according to the degree of the discrepancy. Here, we describe one case of a female with isolated cleft palate and hand malformation who exhibited severe maxillary deficiency until her adolescence and was treated with multiple orthognathic surgeries, including surgically assisted maxillary expansion (surgically assisted rapid palatal expansion), LeFort I osteotomy, and bilateral sagittal split osteotomy in order to correct severe skeletal discrepancy and malocclusion. The treatment resulted in balanced facial appearance and mutually protected occlusion with good stability. The purpose of this case report is to show the orthodontic treatment outcome of 1 patient who exhibited isolated cleft palate and subsequent severe skeletal deformities and malocclusion which was treated by an orthodontic-surgical approach. PMID- 29787303 TI - Where do nanometric micelles stand for biomedical applications? PMID- 29787305 TI - Functional changes of the SCN in spontaneous hypertension but not after the induction of hypertension. AB - The present study investigates the circadian behavior of spontaneously hypertensive rats (SHRs) during the pre-hypertensive and hypertensive stage, with the aim to gain insight into whether observed changes in the functionality of suprachiasmatic nucleus (SCN) in the hypertensive state are cause or consequence of hypertension. Four types of animals were used in this study: (1) SHRs which develop hypertension genetically; (2) their normotensive controls, Wistar Kyoto rats (WKYs); (3) Wistar rats whereby hypertension was surgically induced (2 Kidney 1 Clamp (2K1C) method); and (4) sham-operated control Wistar rats. Period length and activity levels and amplitude changes of locomotor and wheel running activity were determined, in constant conditions, as a measure of the functionality of the SCN. Hereto two conditions were used, constant darkness (0 lux) and constant dim (5 lux) light. SHRs showed a shortened period of their locomotor and running wheel activity rhythms in constant darkness during both pre hypertensive and hypertensive stages and exhibited period lengthening in constant dim light conditions, only during hypertensive stages. Total amount as well as the amplitude of daily running wheel rhythms showed an inverse correlation with the period length, and this relation was significantly different in SHRs compared to WKYs. None of the aforementioned changes in circadian rhythms were observed after the surgical induction of hypertension. The present findings suggest early functional changes of the SCN in the etiology of spontaneous hypertension. PMID- 29787306 TI - Correction to: Development of the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ): A Factor/Facet Version of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). PMID- 29787304 TI - Deterioration of Regional Lung Strain and Inflammation during Early Lung Injury. AB - RATIONALE: The contribution of aeration heterogeneity to lung injury during early mechanical ventilation of uninjured lungs is unknown. OBJECTIVES: To test the hypotheses that a strategy consistent with clinical practice does not protect from worsening in lung strains during the first 24 hours of ventilation of initially normal lungs exposed to mild systemic endotoxemia in supine versus prone position, and that local neutrophilic inflammation is associated with local strain and blood volume at global strains below a proposed injurious threshold. METHODS: Voxel-level aeration and tidal strain were assessed by computed tomography in sheep ventilated with low Vt and positive end-expiratory pressure while receiving intravenous endotoxin. Regional inflammation and blood volume were estimated from 2-deoxy-2-[(18)F]fluoro-d-glucose (18F-FDG) positron emission tomography. MEASUREMENTS AND MAIN RESULTS: Spatial heterogeneity of aeration and strain increased only in supine lungs (P < 0.001), with higher strains and atelectasis than prone at 24 hours. Absolute strains were lower than those considered globally injurious. Strains redistributed to higher aeration areas as lung injury progressed in supine lungs. At 24 hours, tissue-normalized 18F-FDG uptake increased more in atelectatic and moderately high-aeration regions (>70%) than in normally aerated regions (P < 0.01), with differential mechanistically relevant regional gene expression. 18F-FDG phosphorylation rate was associated with strain and blood volume. Imaging findings were confirmed in ventilated patients with sepsis. CONCLUSIONS: Mechanical ventilation consistent with clinical practice did not generate excessive regional strain in heterogeneously aerated supine lungs. However, it allowed worsening of spatial strain distribution in these lungs, associated with increased inflammation. Our results support the implementation of early aeration homogenization in normal lungs. PMID- 29787307 TI - Membrane-based technologies for meeting the recovery of biologically active compounds from foods and their by-products. AB - To date, according to the latest literature inputs, membranes-based technologies (microfiltration, ultrafiltration and nanofiltration) have demonstrated to meet the recovery of biologically active compounds, mainly phenolic compounds and their derivatives, from agro-food products and by-products. The goal of this paper is to provide a critical overview of the on ongoing development works aimed at improving the separation, fractionation and concentration of phenolic compounds and their derivatives from their original sources. The literature data are analyzed and discussed in relation to separation processes, molecule properties, membrane characteristics and key factors affecting the performance of such technologies. Technological advances and improvements over conventional technologies, as well as critical aspects to be further investigated are highlighted and discussed. Finally, a critical outlook about the current status for a large-scale application and the role of these processes from an environmental viewpoint is provided. PMID- 29787308 TI - Acute Respiratory Distress Syndrome: Can Data from the Sick Guide Care for the Healthy? PMID- 29787310 TI - Decreased expression of Na+-H+ exchanger isoforms 1 and 3 in denervated spontaneously hypertensive rat kidney. AB - To determine whether the sympathetic nerve plays a role in the regulation of Na+ H+ exchange (NHE) in the kidney of spontaneously hypertensive rats (SHR), we investigated the expression of NHE and NHE regulatory protein family (NHERF) in the denervated kidneys compared with intact kidneys. Twelve-week-old male SHR and age-matched Wistar Kyoto (WKY) rats were used. SHR were randomly assigned to the renal denervated (RDNX, n = 8) or Sham (n = 8) groups. The protein and mRNA expression of NHE1, NHE3, NHERF1 and NHERF2 were assessed in the kidney of the groups. Following the renal denervation, immunohistochemistry and western blot analysis showed that NHE1 and NHE3 protein were significantly decreased in the kidney compared with Sham group. NHERF1 protein expression was significantly increased in RDNX compared with Sham group, whereas NHERF2 protein expression was significantly decreased after renal denervation. Similar results were observed at the mRNA level of NHE1, NHE3, NHERF1 and NHERF2 expression. The present findings suggest that the renal sympathetic nervous system plays a role in the regulation of NHE1 and NHE3 in the kidney of SHR, and NHERF1 may be involved in the expression of NHE3 in the kidney of SHR. PMID- 29787313 TI - Clinical Nononcologic Applications of PET/CT and PET/MRI in Musculoskeletal, Orthopedic, and Rheumatologic Imaging. AB - OBJECTIVE: With improvements in PET/CT and PET/MRI over the last decade, as well as increased understanding of the pathophysiology of musculoskeletal diseases, there is an emerging potential for PET as a primary or complementary modality in the management of rheumatologic and orthopedic conditions. CONCLUSION: We discuss the role of PET/CT and PET/MRI in nononcologic musculoskeletal disorders, including inflammatory and infectious conditions and postoperative complications. There is great potential for an increased role for PET to serve as a primary or complementary modality in the management of orthopedic and rheumatologic disorders. PMID- 29787309 TI - Predicting Intensive Care Unit Readmission with Machine Learning Using Electronic Health Record Data. AB - RATIONALE: Patients transferred from the intensive care unit to the wards who are later readmitted to the intensive care unit have increased length of stay, healthcare expenditure, and mortality compared with those who are never readmitted. Improving risk stratification for patients transferred to the wards could have important benefits for critically ill hospitalized patients. OBJECTIVES: We aimed to use a machine-learning technique to derive and validate an intensive care unit readmission prediction model with variables available in the electronic health record in real time and compare it to previously published algorithms. METHODS: This observational cohort study was conducted at an academic hospital in the United States with approximately 600 inpatient beds. A total of 24,885 intensive care unit transfers to the wards were included, with 14,962 transfers (60%) in the training cohort and 9,923 transfers (40%) in the internal validation cohort. Patient characteristics, nursing assessments, International Classification of Diseases, Ninth Revision codes from prior admissions, medications, intensive care unit interventions, diagnostic tests, vital signs, and laboratory results were extracted from the electronic health record and used as predictor variables in a gradient-boosted machine model. Accuracy for predicting intensive care unit readmission was compared with the Stability and Workload Index for Transfer score and Modified Early Warning Score in the internal validation cohort and also externally using the Medical Information Mart for Intensive Care database (n = 42,303 intensive care unit transfers). RESULTS: Eleven percent (2,834) of discharges to the wards were later readmitted to the intensive care unit. The machine-learning-derived model had significantly better performance (area under the receiver operating curve, 0.76) than either the Stability and Workload Index for Transfer score (area under the receiver operating curve, 0.65), or Modified Early Warning Score (area under the receiver operating curve, 0.58; P value < 0.0001 for all comparisons). At a specificity of 95%, the derived model had a sensitivity of 28% compared with 15% for Stability and Workload Index for Transfer score and 7% for the Modified Early Warning Score. Accuracy improvements with the derived model over Modified Early Warning Score and Stability and Workload Index for Transfer were similar in the Medical Information Mart for Intensive Care-III cohort. CONCLUSIONS: A machine learning approach to predicting intensive care unit readmission was significantly more accurate than previously published algorithms in both our internal validation and the Medical Information Mart for Intensive Care-III cohort. Implementation of this approach could target patients who may benefit from additional time in the intensive care unit or more frequent monitoring after transfer to the hospital ward. PMID- 29787315 TI - Medicolegal-Malpractice and Ethical Issues in RadiologyIf I Don't Adhere to Every Detail in an American College of Radiology Parameter, Am I Vulnerable to Malpractice Litigation? PMID- 29787314 TI - Main Pancreatic Duct Dilatation: Isolated or Not? PMID- 29787316 TI - Reply to "Prostate Cancer and Prostate Imaging Reporting and Data System Category 3 Lesions Identified at Multiparametric Prostate MRI". PMID- 29787317 TI - Identifying and Disseminating More Best Practices. PMID- 29787318 TI - Prostate Cancer and Prostate Imaging Reporting and Data System Category 3 Lesions Identified at Multiparametric Prostate MRI. PMID- 29787319 TI - Usefulness of multiple electrode aggregometry as a screening tool for bleeding disorders in a pediatric hospital. AB - Platelet function testing is a cornerstone in the diagnostic investigation of patients with a bleeding history. Multiple electrode aggregometry (MEA) has been shown to detect von Willebrand disease (VWD), platelet function disorders, and drug-induced bleeding disorders. However, there are few studies supporting its successful use in children. We have implemented and used MEA over 3 years in our hemostasis laboratory in order to study its usefulness to supplement and expedite diagnosis. This is a retrospective, single-center, cohort study of 109 hospitalized children who underwent a laboratory investigation of hemostasis and either had a reported bleeding history or an abnormal bleeding episode. Plasmatic coagulation testing, blood counts, plasmatic von Willebrand testing, platelet function analyzer (PFA-100), and impedance aggregometry (MEA) were performed in all children. Light transmission aggregometry testing was performed as needed. In 41 cases (37.6%), a working diagnosis was made; a primary hemostatic disorder was detected in 35 children (VWD (n = 16), platelet disorder (n = 15), and valproic acid therapy-induced bleeding disorder (n = 3), acetylsalicylic acid-related bleeding (n = 1). In patients diagnosed with VWD, MEA ristocetin-induced platelet aggregation test (RISTO) high test revealed abnormally low aggregation in six patients (43.8%); whereas in patients diagnosed with a platelet function disorder, abnormally low values were found by MEA in only three children (20%). Three of the four children with laboratory evidence of drug-induced platelet dysfunction had abnormalities on MEA. There were no cases in which an abnormal MEA result was used to make a previously undetermined diagnosis. Retrospectively, MEA has demonstrated limited additional diagnostic value beyond standard laboratory testing for detecting defects of primary hemostasis in children. PMID- 29787320 TI - Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia. AB - INTRODUCTION: Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths witnessed in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated-dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML. Areas covered: Addition of fractionated GO to chemotherapy significantly improved event-free survival of newly diagnosed AML patients with favorable and intermediate cytogenetic-risk disease. GO monotherapy also prolonged survival in newly diagnosed unfit patients and relapse-free survival in relapsed/refractory AML. This new dosing schedule was associated with decreased incidence of hepatotoxicity, veno-occlusive disease, and early mortality. Expert commentary: GO represents the first drug-antibody conjugate approved (twice) in the United States for AML. Its re-emergence adds a valuable agent back into the armamentarium for AML. The approval of GO as well as three other agents for AML in 2017 highlights the need for rapid cytogenetic and molecular characterization of AML and incorporation into new treatment algorithms. PMID- 29787321 TI - Enhanced Depth Imaging by High-Resolution Spectral Domain Optical Coherence Tomography in Tubercular Multifocal Serpiginoid Choroiditis. AB - PURPOSE: To report the choroidal changes by enhanced depth imaging optical coherence tomography (EDI-OCT) in tubercular multifocal serpiginoid choroiditis (MSC). METHODS: Prospective study of 20 patients (23 eyes) with active MSC who underwent simultaneous fundus autofluorescence and EDI-OCT imaging at regular visits. RESULTS: Eyes with acute lesions demonstrated diffuse choroidal thickening at presentation, which decreased significantly as the lesions healed. Additionally, the region of (thickened) choroid just beneath the active choroiditis lesion demonstrated a localized area of mixed reflectivity (a central hyperreflectivity surrounded by a zone of hyporeflectivity), suggesting choroidal involvement deeper to choriocapillaris. Once the lesions healed, the choroid under the scar showed a localized thinning, along with outer retinal layers loss. CONCLUSION: EDI-OCT highlighted diffuse and localized choroidal structural changes in MSC as the lesions evolved from acute to healed stage, providing an adjunct to clinical examination for monitoring response to therapy. PMID- 29787322 TI - Short-Term Deposition of PM2.5 Particles on Contact Lens Surfaces: Effect on Oxygen Permeability and Refractive Index. AB - PURPOSES: To identify the deposition of fine (<=2.5 MUm diameter) particulate matter (PM) particles (PM2.5) on contact lens surfaces and to investigate the effects of such deposition on the oxygen permeability (OP) and refractive index (RI) of contact lenses. METHODS: A total of 36 contact lenses, including rigid gas permeable (RGP) lens and soft contact lens (SCL), were investigated. RGP lens (n=12) and SCL (n=12) (experimental group) were incubated in a PM2.5 solution for 24 h, after which PM2.5-treated RGP lens (n=6) and SCL (n=6) were further washed for 1 h in phosphate-buffered saline (PBS). All lenses were examined by field emission scanning electron microscopy. OP and RI of all lenses were measured. RESULTS: Average-sized PM2.5 particles deposited on RGP contact lens and SCL surfaces after immersion in the PM2.5 solution were 3.192 +/- 1.637 and 2.158 +/- 1.187/100 MUm2, respectively. On RGP lens surfaces, we observed both large (>=2.5 um diameter) and small (PM2.5) particles. PM2.5 particles were deposited in diffuse patterns, primarily along the honeycomb structural border of SCL, while no PM2.5 particles were found in the honeycomb hole of SCL surfaces. Washing in PBS removed the larger PM particles from RGP lens surfaces, but left copious amounts of PM2.5 particles. In contrast, nearly all PM particles were removed from SCL surfaces after PBS washing. OP values of RGP lens and SCL appeared to be unchanged by PM2.5 deposition. RI values increased in both RGP lens and SCL groups after PM2.5 deposition. However, these increases were not statistically significant, suggesting that PM2.5 deposition itself does not cause fluctuations in contact lens RI. CONCLUSIONS: Deposition of PM2.5 particles on contact lens surfaces varies according to lens material. PM2.5 particles deposited on SCL, but only large particles on RGP surfaces were able to be removed by washing in PBS and did not appear to alter OP and RI of either lens type. PMID- 29787324 TI - Provider Perspectives on Topical Analgesics. AB - Topical analgesics are effective and alternative means to systemic therapy, often minimizing the adverse drug effects and complications of systemic analgesic use. Despite the number of available topical analgesics, there is little direction provided in practice guidelines on their appropriate use and little is known about patterns of their prescribing. To begin understanding these knowledge gaps, we sought provider perspectives on topical analgesic use at a large academic medical center. This electronic survey seeks to explore the perceptions and prescription patterns of topical analgesics among prescribers in a large academic medical center, where the availability of topical analgesics varies. Among topical analgesics, lidocaine (78%) is prescribed more frequently than nonsteroidal anti-inflammatory drugs (NSAIDs; 41%) or morphine (3%). Formulations and indications of use varied between faculty physicians and nonfaculty providers. Reasons for prescribing were largely based on anecdotal experience. Based on the survey results, it is clear that more topical agents are needed to manage pain; however, so too is guidance on appropriate prescribing. PMID- 29787323 TI - The role of vaccines in fighting antimicrobial resistance (AMR). AB - The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR. PMID- 29787325 TI - Barriers to Self-Reporting Patient Safety Incidents by Paramedics: A Mixed Methods Study. AB - BACKGROUND: A minimal amount of research exists examining the extent to which patient safety events occur within paramedicine and even fewer studies investigating patient safety systems for self-reporting by paramedics. The purpose of this study was to identify barriers to paramedic self-reporting of patient safety incidents (PSIs). METHODS: We randomly distributed paper-based surveys among 1,153 paramedics in an Ontario region in Canada. The survey described one of 5 different PSI clinical scenarios (near miss, adverse event, and minor, major or critical patient care variances) and listed 18 potential barriers to self-reporting PSIs as statements presented for rating on a 5-point Likert scale (very significant = 1 - very insignificant = 5). We invited comments on PSI self-reporting with 2 open-ended questions. We analyzed data with descriptive statistics, chi-square tests and Kruskal-Wallis H test. We used an inductive approach to qualitatively analyze emerging themes. RESULTS: We received responses from 1,133 paramedics (98.3%). Almost one third (28.4%) were Advanced Care Paramedics and 45.1% had >10 years' experience. The top 5 barriers to PSI self-reporting (very significant or significant, %) were the fear of being: punished (81.4%), suspended (79.6%), terminated (79.1%), investigated by Ministry of Health and Long-Term Care (78.4%), and decertified (78.0%). Overall, 64.1% responded they would self-report a given PSI. Intention to self-report a PSI varied according to scenario (22.8% near miss, 46.6% adverse event, 74.4% minor, 92.6% major, 95.6% critical). No association was found between level of training (p = 0.55) or years of experience (p = 0.10) and intention to self-report a PSI. Seven themes to improve PSI self-reporting by paramedics emerged from the qualitative data. CONCLUSIONS: A high proportion of fear-based barriers to self reporting of PSIs exist among this study population. This suggests that a culture change is needed to facilitate the identification of future patient safety threats. PMID- 29787326 TI - Application of High-Throughput Flow Cytometry in Early Drug Discovery: An AstraZeneca Perspective. AB - Flow cytometry is a powerful tool providing multiparametric analysis of single cells or particles. The introduction of faster plate-based sampling technologies on flow cytometers has transformed the technology into one that has become attractive for higher throughput drug discovery screening. This article describes AstraZeneca's perspectives on the deployment and application of high-throughput flow cytometry (HTFC) platforms for small-molecule high-throughput screening (HTS), structure-activity relationship (SAR) and phenotypic screening, and antibody screening. We describe the overarching HTFC workflow, including the associated automation and data analysis, along with a high-level overview of our HTFC assay portfolio. We go on to discuss the practical challenges encountered and solutions adopted in the course of our deployment of HTFC, as well as future enhancements and expansion of the technology to new areas of drug discovery. PMID- 29787327 TI - Establishing and Evaluating Autoverification Rules with Intelligent Guidelines for Arterial Blood Gas Analysis in a Clinical Laboratory. AB - Arterial blood gas (ABG) analysis is important for acutely ill patients and should be performed by qualified laboratorians. The existing manual verifications are tedious, time-consuming, and prone to send wrong reports. Autoverification uses computer-based rules to verify clinical laboratory test results without manual review. To date, no data are available on the use of autoverification for ABG analysis. All autoverification rules were established according to AUTO10-A. Additionally, the rules were established using retrospective patient data, and then validated by actual clinical samples in a "live" environment before go-live. The average autoverification passing rate was 75.5%. The turnaround time (TAT) was reduced by 33.3% (27 min vs 18 min). Moreover, the error rate fell to 0.05% after implementation. Statistical analysis resulted in a kappa statistic of 0.92 ( p < 0.01), indicating close agreement between autoverification and senior technician verification, and the chi-square value was 22.4 ( p < 0.01), indicating that the autoverification error rate was lower than the manual verification error rate. Results showed that implementing autoverification rules with intelligent guidelines for ABG analysis of patients with critical illnesses could decrease the number of samples requiring manual verification, reduce TAT, and eliminate errors, allowing laboratorians to concentrate more time on abnormal samples, patient care, and collaboration with physicians. PMID- 29787329 TI - Sensitivity to change and responsiveness of the Segmental Assessment of Trunk Control (SATCo) in children with spinal cord injury. AB - PURPOSE: The purpose of this study was to assess the sensitivity and responsiveness of the Segmental Assessment of Trunk Control (SATCo) for evaluating trunk control in children with spinal cord injury (SCI) receiving activity-based locomotor training (AB-LT). METHODS: Prospective study of nine outcomes for consecutively enrolled children in outpatient AB-LT. To evaluate sensitivity to change, linear-mixed models were constructed and adjusted for covariates: age at and time since SCI. To evaluate responsiveness, standardized response means and 95% confidence intervals were estimated per outcome. RESULTS: SATCo scores increased significantly (p < 0.05) regardless of chronicity, initial score, and injury level. The SATCo was the most responsive measure and the only outcome demonstrating a large effect size after 3 months of therapy. CONCLUSIONS: Children with SCI receiving AB-LT improved trunk control regardless of chronicity, initial impairment, or prior experience. SATCo sensitivity and responsiveness support its usefulness in measuring trunk control in children with SCI. PMID- 29787328 TI - Megakaryocyte apoptosis in immune thrombocytopenia. AB - The mechanisms of platelet underproduction in immune thrombocytopenia (ITP) remain unknown. While the number of megakaryocytes is normal or increased in ITP bone marrow, further studies of megakaryocyte integrity are needed. Megakaryocytes are responsible for the production of platelets in the bone marrow, and they are possible targets of immune-mediated injury in ITP. Since the biological process of megakaryocyte apoptosis impacts platelet production, we investigated megakaryocyte DNA fragmentation as a marker of apoptosis from ITP bone marrow biopsies. Archived bone marrow biopsy specimens from ITP patients, bone marrow specimens from controls with normal platelet counts, and bone marrow specimens from thrombocytopenic controls with myelodysplastic syndrome (MDS) were evaluated. Sections were stained with anti-CD61 for megakaryocyte enumeration, and terminal deoxynucleotidyl transferase dUTP nick-end labeling was used as an apoptotic indicator. In ITP patients, megakaryocyte apoptosis was reduced compared to nonthrombocytopenic controls. Megakaryocyte apoptosis was similarly reduced in thrombocytopenic patients with MDS. These results suggest a link between megakaryocyte apoptosis and platelet production. PMID- 29787330 TI - The Myth of the Well-Known Client. AB - A common idiomatic phrase in mental health care is "well known" client, patient, or service user. This phrase is often followed by "to mental health services" or some such, suggesting that a "service" can really know anything. Notwithstanding mental health services, especially public ones are a repository for a lot of information, such as facts about people, their service use, diagnosis, notes and assessments of various kinds; this conglomeration of information is not knowing, any more than a library may be "knowing". Knowing is a distinctly human activity. This paper will argue that this phrase is arrogant, a signifier of ignorance and ought to be relegated to history or back room banter with phrases like "frequent flyer", "bed seeker" and other derogatory and objectifying language. PMID- 29787331 TI - A Customizable, Low-Cost Perfusion System for Sustaining Tissue Constructs. AB - The fabrication of engineered vascularized tissues and organs requiring sustained, controlled perfusion has been facilitated by the development of several pump systems. Currently, researchers in the field of tissue engineering require the use of pump systems that are in general large, expensive, and generically designed. Overall, these pumps often fail to meet the unique demands of perfusing clinically useful tissue constructs. Here, we describe a pumping platform that overcomes these limitations and enables scalable perfusion of large, three-dimensional hydrogels. We demonstrate the ability to perfuse multiple separate channels inside hydrogel slabs using a preprogrammed schedule that dictates pumping speed and time. The use of this pump system to perfuse channels in large-scale engineered tissue scaffolds sustained cell viability over several weeks. PMID- 29787332 TI - Comparison of Nine Tools for Screening Drug-Drug Interactions of Oral Oncolytics. AB - PURPOSE: Patients with cancer are an especially vulnerable population to potential drug-drug interactions (DDIs). This makes it important to adequately screen them for DDIs. The objective of this study was to compare the abilities of nine DDI screening tools to detect clinically relevant interactions with oral oncolytics. METHODS: Subscription-based tools (ie, PEPID, Micromedex, Lexicomp, Facts & Comparisons) and free tools (ie, Epocrates Free, Medscape, Drugs.com, RxList, WebMD) were compared for their abilities to detect clinically relevant DDIs for 145 drug pairs including an oral oncology agent. Clinical relevance was determined by a pharmacist using Stockley's Drug Interactions. Descriptive statistics were calculated for each tool, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and then compared grouped by free or subscription-based tools for the secondary analysis and analyzed via generalized estimating equations. RESULTS: For individual metrics, PPV had overall higher values (0.88 to 0.97) relative to the low values included for sensitivity (0.65 to 0.96), specificity (0.53 to 0.93) and NPV (0.38 to 0.83). The top-performing subscription and free tools, Lexicomp and Drugs.com, had no statistically significant differences in performance. Overall, subscription tools had a significantly higher sensitivity (0.85 +/- 0.017 v 0.78 +/- 0.017; P = .0082) and NPV (0.57 +/- 0.039 v 0.48 +/- 0.032; P = .031) than free tools. No differences were observed between the specificity and PPV. CONCLUSION: Due to the low performance of some tools for sensitivity, specificity, and NPV, individual performance should be examined and prioritized on the basis of the intended use when selecting a DDI tool. If a strong performing subscription-based tool is unavailable, a strong-performing free option, like Drugs.com, is available. PMID- 29787334 TI - Global rotavirus vaccine introductions and coverage: 2006 - 2016. AB - An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and lower-middle income countries. Since 2009 the World Health Organization (WHO) recommends the use of rotavirus vaccines in all national immunization programs. This review compares rotavirus vaccine (RV) introductions and vaccine coverage by region, country income status and Gavi-eligibility from 2006-2016. Gross National Income data from the World Bank and surviving infant population from United Nations Population Division was obtained for 2016. Data from WHO were collected on rotavirus vaccine coverage, national immunization schedules, and new vaccine introductions for 2016 while estimated rotavirus deaths were collected for 2013, the last year of available WHO data. As of December 2016, the majority of countries (57%, 110/194) had not introduced universal rotavirus vaccine despite WHO's 2009 recommendation to do so. Countries in the WHO African region had the greatest proportion of introductions (37%, 31/84) by December 2016 and a great majority of these (77%, 24/31) were supported by new vaccine introduction (NVI) grants from Gavi. Almost half (48%) of global introductions were in low and lower middle income Gavi-eligible and Gavi-graduating countries. Conversely, countries in the Southeast Asia WHO region and those not eligible for Gavi NVI support have been slow to introduce rotavirus vaccine. High-income countries, on average, had poorer rotavirus vaccine coverage compared to low and lower-middle income countries. The over-representation of African countries within the Gavi subset and high estimated rotavirus deaths in these African countries, likely explains why introduction efforts have been focused in this region. While much progress has been made with the integration and implementation of rotavirus vaccine into national immunization programs, 110 countries representing 69% of the global birth cohort had yet to introduce the vaccine by December 2016. PMID- 29787335 TI - Platelet proteomics: from discovery to diagnosis. AB - INTRODUCTION: Platelets are the smallest cells within the circulating blood with key roles in physiological hemostasis and pathological thrombosis regulated by the onset of activating/inhibiting processes via receptor responses and signaling cascades. Areas covered: Proteomics as well as genomic approaches have been fundamental in identifying and quantifying potential targets for future diagnostic strategies in the prevention of bleeding and thrombosis, and uncovering the complexity of platelet functions in health and disease. In this article, we provide a critical overview on current functional tests used in diagnostics and the future perspectives for platelet proteomics in clinical applications. Expert commentary: Proteomics represents a valuable tool for the identification of patients with diverse platelet associated defects. In-depth validation of identified biomarkers, e.g. receptors, signaling proteins, post translational modifications, in large cohorts is decisive for translation into routine clinical diagnostics. PMID- 29787333 TI - Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials. AB - PURPOSE: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. METHODS: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. RESULTS: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). CONCLUSION: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials. PMID- 29787336 TI - Breast Is Best . . . Except When It's Not. PMID- 29787338 TI - Learning to cope with mirror movements in unilateral spastic cerebral palsy: a brief report. AB - PURPOSE: Mirror movements (MM) in unilateral spastic cerebral palsy (USCP) interfere with many bimanual activities of daily living. METHODS: Here, we developed a specific bimanual therapeutic regimen, focusing on asymmetric simultaneous movements of the two hands. Twelve children (6-17 years old; complete data available in ten children) with USCP and MM were included. RESULTS: After three weeks of inpatient rehabilitation, we observed significant improvements for two self-defined bimanual goal activities (Goal Attainment Scaling, Canadian Occupational Performance Measure) and for bimanual performance in general (Assisting Hand Assessment). These improvements were still present 6 months later. In contrast, even immediately after therapy, the severity of MM had not changed. CONCLUSIONS: Hence, targeted bimanual therapy improved bimanual performance, but did not lead to a reduction of MM. The results of this pilot study might suggest that children with MM benefit more from acquiring strategies to cope with MM than by an active training which aimed to reduce MM. PMID- 29787337 TI - Multiple Functions of Lysyl Oxidase Like-2 in Oral Fibroproliferative Processes. AB - Gingival overgrowth is a side effect of certain medications, including calcium channel blockers, cyclosporin A, and phenytoin. Phenytoin-induced gingival overgrowth is fibrotic. Lysyl oxidases are extracellular enzymes that are required for biosynthetic cross-linking of collagens, and members of this enzyme family are upregulated in fibrosis. Previous studies in humans and in a mouse model of phenytoin-induced gingival overgrowth have shown that LOXL2 is elevated in the epithelium and connective tissue in gingival overgrowth tissues and not in normal tissues. Here, using a novel LOXL2 isoform-selective inhibitor and knockdown studies in loss- and gain-of-function studies, we investigated roles for LOXL2 in promoting cultures of human gingival fibroblasts to proliferate and to accumulate collagen. Data indicate that LOXL2 stimulates gingival fibroblast proliferation, likely by a platelet-derived growth factor B receptor-mediated mechanism. Moreover, collagen accumulation was stimulated by LOXL2 enzyme and inhibited by LOXL2 inhibitor or gene knockdown. These studies suggest that LOXL2 could serve as a potential therapeutic target to address oral fibrotic conditions. PMID- 29787339 TI - Outcomes in pediatric powered endoscopic dacryocystorhinostomy: a single-center experience. AB - PURPOSE: The purpose of the article is to report the outcomes of powered endoscopic dacryocystorhinostomy (PEnDCR) in pediatric patients. METHODS: A single-center, single surgeon, retrospective, interventional, non-comparative case series was performed on all pediatric patients who underwent PEnDCR between July 2014 and July 2017. Patients with associated congenital anomalies like single punctum agenesis or lacrimal fistula were excluded. Surgery was performed as per standard protocols published earlier. Data collected include demographics, clinical presentations, past interventions, indications for the surgery, intraoperative and postoperative complications, postoperative ostium characteristics, and anatomical and functional success. RESULTS: Ninety-one eyes of 83 children underwent PEnDCR during the study period. Mean age was 8.32 years and epiphora was the most common presentation (81%, 74/91). The most common indication for PEnDCR was persistent congenital nasolacrimal duct obstruction refractory to earlier interventions of probing or intubation. Postoperative ostium assessment at 4 weeks showed a well-healed ostium with a dynamic internal common opening in 86.8% of the eyes. Edge granulomas of the ostium were the most common abnormal finding in the postoperative period (9.8%, 9/91) and all except one could be managed conservatively. At 6 months follow-up, five eyes showed anatomical failure and additional two eyes showeXd functional failure. Two of anatomical failure group and one of functional failure underwent a second intervention. The final anatomical and functional success were noted in 96.7% (88/91) and 95.6% (87/91), respectively. CONCLUSIONS: This study shows that PEnDCR is a safe surgery for pediatric populations with a high success rate of beyond 95%. PMID- 29787340 TI - Correlation between thyroidal and peripheral blood total T cells, CD8+ T cells, and CD8+ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves' ophthalmopathy. AB - : Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8+ T cells and autoimmunity against calsequestrin-1 (CASQ) 1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. MATERIALS AND METHODS: Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. RESULTS: We found a positive correlation between thyroidal CD8+ T cells and CD8+ T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. CONCLUSIONS: Our observations provide further evidence for a possible role of thyroidal CD8+ T cells, CD8+ T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO. PMID- 29787341 TI - Standardized outcome measures for cerebral palsy among physiotherapists in southwestern Nigeria: awareness, use, barriers, and facilitators. AB - The use of outcome measures for assessing progress in the management and treatment of cerebral palsy (CP) is widely recommended. This study was, therefore, carried out to determine awareness and use of standardized outcome measures among physiotherapists managing CP in Nigeria. Barriers to and facilitators for the use of outcome measures were also investigated. This was a descriptive study involving 138 physiotherapists from selected hospitals in southwestern Nigeria. A self-administered questionnaire was used to obtain relevant information on socio-demographics, awareness, use, barriers to, and facilitators for the use of seven standardized outcome measures. The Gross Motor Function Measure was the most recognized (78.9%) and commonly used (58%) outcome measure, while the Paediatric Outcomes Data Collection Instrument (23.2%) and the Paediatric Evaluation of Disability Inventory (10.9%) were the least recognized and least used, respectively. The greatest perceived facilitators were familiarity (87.7%), positive attitude (87.7%), and that outcome measures allow for a balanced clinical assessment (89.1%). The greatest perceived barriers identified were the need for extra accommodation to apply outcome measures (63%) and time consumption on the part of patients (44.2%). Many physiotherapists in this study identified the standardized outcome measures, but fewer used them irrespective of educational status and years of work experience. Generally, there was a positive attitude toward the use of outcome measures. The use of outcome measures should be promoted among physiotherapists in Nigeria, through training programs and translation into the native languages, to effectively assess, manage, and monitor the progress of patients with CP, putting into consideration barriers and facilitators. PMID- 29787342 TI - Learning facts during aging: the benefits of curiosity. AB - : Background/study context: Recent studies have shown that young adults better remember factual information they are curious about. It is not entirely clear, however, whether this effect is retained during aging. Here, the authors investigated curiosity-driven memory benefits in young and elderly individuals. METHODS: In two experiments, young (age range 18-26) and older (age range 65-89) adults read trivia questions and rated their curiosity to find out the answer. They also attended to task-irrelevant faces presented between the trivia question and the answer. The authors then administered a surprise memory test to assess recall accuracy for trivia answers and recognition memory performance for the incidentally learned faces. RESULTS: In both young and elderly adults, recall performance was higher for answers to questions that elicited high levels of curiosity. In Experiment 1, the authors also found that faces presented in temporal proximity to curiosity-eliciting trivia questions were better recognized, indicating that the beneficial effects of curiosity extended to the encoding of task-irrelevant material. CONCLUSIONS: These findings show that elderly individuals benefit from the memory-enhancing effects of curiosity. This may lead to the implementation of learning strategies that target and stimulate curiosity in aging. PMID- 29787343 TI - Predicting Financial Distress in Acute Care Hospitals. AB - Hospitals continue to face financial pressures from healthcare reform and heightened competition. In this study, our objective was to quantify the financial distress in acute care hospitals in Texas, applying multivariate logistic regression in a four-year longitudinal analysis. Of the 310 acute care hospitals, 50 (16.1%) were in financial distress in the most recent year, up considerably year over year. Distressed hospitals had fewer beds, lower patient acuity, and less outpatient revenues than those in good financial condition. Administrators should identify business turnaround strategies for combating distress to avoid potential closure. PMID- 29787344 TI - A Survey of Current Practice of Informed Consent in Iranian Hospitals. AB - BACKGROUND: Informed consent is legal and ethical process which is considered as important issue in quality of patient's treatment. The aim of the current study was to assess current informed consent of patients admitted in Iranian selected Hospitals, 2016. MATERIALS AND METHODS: This cross-sectional study was conducted on 2150 patients admitted in 11 public Hospitals. Data was collected using a dichotomous questionnaire with 30 questions. Statistical analysis was done using SPSS software (version 18). RESULTS: The results shown that 46% of patients had medium perception about informed consent, 44% believed to get insufficient information and 66% claimed to have active participation in treatment process. The significant associations were found between some dimensions and important parameters: Understanding of information dimension and education level (p = 0.008), Participation (in decision-making) dimension and type of hospitalization (p = 0.01), and level of patients' information dimension with resident address (p = 0.027) and medical specialty (p < 0.001). CONCLUSION: In our study the current informed consent of patients wasn't in desirable condition. The Necessary measures are required to achieve a level that the patients' informed consent convert to informed choices. Hospital healthcare team need to take proper actions such as give proper information, patient training, sufficient information and etc. PMID- 29787345 TI - The Link Between Self-Dehumanization and Immoral Behavior. AB - People perceive morality to be distinctively human, with immorality representing a lack of full humanness. In eight experiments, we examined the link between immorality and self-dehumanization, testing both (a) the causal role of immoral behavior on self-dehumanization and (b) the causal role of self-dehumanization on immoral behavior. Studies 1a to 1d showed that people feel less human after behaving immorally and that these effects were not driven by having a negative experience but were unique to experiences of immorality (Study 1d). Studies 2a to 2c showed that self-dehumanization can lead to immoral and antisocial behavior. Study 3 highlighted how self-dehumanization can sometimes produce downward spirals of immorality, demonstrating initial unethical behavior leading to self dehumanization, which in turn promotes continued dishonesty. These results demonstrate a clear relationship between self-dehumanization and unethical behavior, and they extend previous theorizing on dehumanization. PMID- 29787346 TI - 'Slipped Sandwich' Model for Chitin and Chitosan Perception in Arabidopsis. AB - Chitin, a linear polymer of N-acetyl-d-glucosamine, and chitosans, fully or partially deacetylated derivatives of chitin, are known to elicit defense reactions in higher plants. We compared the ability of chitin and chitosan oligomers and polymers (chitin oligomers with degree of polymerization [DP] 3 to 8; chitosan oligomers with degree of acetylation [DA] 0 to 35% and DP 3 to 15; chitosan polymers with DA 1 to 60% and DP approximately 1,300) to elicit an oxidative burst indicative of induced defense reactions in Arabidopsis thaliana seedlings. Fully deacetylated chitosans were not able to trigger a response; elicitor activity increased with increasing DA of chitosan polymers. Partially acetylated chitosan oligomers required a minimum DP of 6 and at least four N acetyl groups to trigger a response. Invariably, elicitation of an oxidative burst required the presence of the chitin receptor AtCERK1. Our results as well as previously published studies on chitin and chitosan perception in plants are best explained by a new general model of LysM-containing receptor complexes in which two partners form a long but off-set chitin-binding groove and are, thus, dimerized by one chitin or chitosan molecule, sharing a central GlcNAc unit with which both LysM domains interact. To verify this model and to distinguish it from earlier models, we assayed elicitor and inhibitor activities of selected partially acetylated chitosan oligomers with fully defined structures. In contrast to the initial 'continuous groove', the original 'sandwich', or the current 'sliding mode' models for the chitin/chitosan receptor, the here-proposed 'slipped sandwich' model-which builds on these earlier models and represents a consensus combination of these-is in agreement with all experimental observations. PMID- 29787347 TI - STP Position Paper: Recommended Best Practices for Sampling, Processing, and Analysis of the Peripheral Nervous System (Nerves and Somatic and Autonomic Ganglia) during Nonclinical Toxicity Studies. AB - Peripheral nervous system (PNS) toxicity is surveyed inconsistently in nonclinical general toxicity studies. These Society of Toxicologic Pathology "best practice" recommendations are designed to ensure consistent, efficient, and effective sampling, processing, and evaluation of PNS tissues for four different situations encountered during nonclinical general toxicity (screening) and dedicated neurotoxicity studies. For toxicity studies where neurotoxicity is unknown or not anticipated (situation 1), PNS evaluation may be limited to one sensorimotor spinal nerve. If somatic PNS neurotoxicity is suspected (situation 2), analysis minimally should include three spinal nerves, multiple dorsal root ganglia, and a trigeminal ganglion. If autonomic PNS neuropathy is suspected (situation 3), parasympathetic and sympathetic ganglia should be assessed. For dedicated neurotoxicity studies where a neurotoxic effect is expected (situation 4), PNS sampling follows the strategy for situations 2 and/or 3, as dictated by functional or other compound/target-specific data. For all situations, bilateral sampling with unilateral processing is acceptable. For situations 1-3, PNS is processed conventionally (immersion in buffered formalin, paraffin embedding, and hematoxylin and eosin staining). For situation 4 (and situations 2 and 3 if resources and timing permit), perfusion fixation with methanol-free fixative is recommended. Where PNS neurotoxicity is suspected or likely, at least one (situations 2 and 3) or two (situation 4) nerve cross sections should be postfixed with glutaraldehyde and osmium before hard plastic resin embedding; soft plastic embedding is not a suitable substitute for hard plastic. Special methods may be used if warranted to further characterize PNS findings. Initial PNS analysis should be informed, not masked ("blinded"). Institutions may adapt these recommendations to fit their specific programmatic requirements but may need to explain in project documentation the rationale for their chosen PNS sampling, processing, and evaluation strategy. PMID- 29787348 TI - Characteristics of Nasal Septal Cartilage-Derived Progenitor Cells during Prolonged Cultivation. AB - Objective To produce alternate cell sources for tissue regeneration, human nasal septal cartilage-derived progenitor cells (NSPs) were tested to identify whether these cells meet the criteria of cartilage progenitor cells. We also evaluated the effects of prolonged cultivation on the characteristics of NSPs. Study Design In vitro study. Setting Academic research laboratory. Methods NSPs were isolated from discarded human nasal septal cartilage. NSPs were cultured for 10 passages. The expression of septal progenitor cell surface markers was assessed by fluorescence-activated cell sorting. Cell proliferation was measured with a cell counting kit. Cytokine secretion was analyzed with multiplex immunoassays. Chondrogenic differentiation of NSPs without differentiation induction was analyzed with type II collagen immunohistochemistry. Cartilage-specific protein expression was evaluated by Western blotting. Under osteo- and adipodifferentiation media, 2 lineage differentiation potentials were evaluated by histology and gene expression analysis. Results Surface epitope analysis revealed that NSPs are positive for mesenchymal stem cells markers and negative for hematopoietic cell markers. Cultured NSPs showed sufficient cell expansion and chondrogenic potential, as demonstrated by immunostaining and expression of cartilage-specific protein. IL-6, IL-8, and transforming growth factor beta were secreted by over 200 pg/mL. The osteo- and adipodifferentiation potentials of NSPs were identified by histology and specific gene expression. The aforementioned characteristics were not influenced by prolonged cultivation. Conclusion NSPs represent an initial step toward creating a cell source from surgically discarded tissue that may prove useful in cartilage regeneration. PMID- 29787349 TI - Head and Neck Cancer Patients: Rates, Reasons, and Risk Factors for 30-Day Unplanned Readmission. AB - Objective To analyze rates, risk factors, and complications for 30-day readmission among head and neck cancer (HNC) patients. Methods Retrospective review of administrative records from Vizient (Irving, Texas) Clinical Data Base/Resource Manager on HNC patients who underwent a head and neck surgical procedure from January 2013 through September 2015 at 176 academic and community medical centers. Results Of the 18,121 patients included in the study, 2502 patients were readmitted within 30 days (13.8%). Mean time to readmission was 11 +/- 8.2 days. Cancer of the hypopharynx, oropharynx, pharynx, and larynx all had higher odds of readmission compared to oral cavity (odds ratio [OR], 1.8, 1.7, 1.6, and 1.5; 95% confidence interval [CI], 1.4-2.2, 1.4-1.9, 1.2-2.3, and 1.3 1.7, respectively). Consistent with this, flap procedures and laryngectomy had the highest odds of readmission (OR, 1.4 and 1.3; 95% CI, 1.3-1.6 and 1.0-1.5 vs glossectomy, respectively). The most common surgical causes for readmission were postoperative infection (17.6%) and surgical wound dehiscence (16.8%), which most commonly presented on postdischarge days 4 to 5. Acute cardiac events occurred in up to 15.4% of patients depending on complexity of surgery. Dysphagia and electrolyte disturbances were common (15.8% and 15.4%, respectively); patients with these complications typically presented earlier, between days 3 and 4. Discussion Patients with HNC are at high risk of readmission. The cancer subsite and procedure significantly influenced the risk, rate, and reason for readmission. Implications for Practice Findings from this study can help quality improvement and patient safety administrators develop interventions that uniquely target HNC populations. PMID- 29787350 TI - Spatial Analysis of Rice Blast in China at Three Different Scales. AB - In this study, spatial analyses were conducted at three different scales to better understand the epidemiology of rice blast, a major rice disease caused by Magnaporthe oryzae. At the regional scale, across the major rice production regions in China, rice blast incidence was monitored on 101 dates at 193 stations from 10 June to 10 September during 2009 to 2014, and surveyed in 143 fields in September 2016; at the county scale, three surveys were done covering one to five counties in 2015 to 2016; and, at the field scale, blast was evaluated in six fields in 2015 to 2016. Spatial cluster and hot spot analyses were conducted in the geographic information system on the geographical pattern of the disease at regional scale, and geostatistical analysis was performed at all three scales. Cluster and hot spot analyses revealed that high-disease areas were clustered in mountainous areas in China. Geostatistical analyses detected spatial dependence of blast incidence with influence ranges of 399 to 1,080 km at regional scale and 5 to 10 m at field scale but not at county scale. The spatial patterns at different scales might be determined by inherent properties of rice blast and environmental driving forces, and findings from this study provide helpful information to sampling and management of rice blast. PMID- 29787352 TI - Statistical Learning Creates Novel Object Associations via Transitive Relations. AB - A remarkable ability of the cognitive system is to make novel inferences on the basis of prior experiences. What mechanism supports such inferences? We propose that statistical learning is a process through which transitive inferences of new associations are made between objects that have never been directly associated. After viewing a continuous sequence containing two base pairs (e.g., A-B, B-C), participants automatically inferred a transitive pair (e.g., A-C) where the two objects had never co-occurred before (Experiment 1). This transitive inference occurred in the absence of explicit awareness of the base pairs. However, participants failed to infer the transitive pair from three base pairs (Experiment 2), showing the limits of the transitive inference (Experiment 3). We further demonstrated that this transitive inference can operate across the categorical hierarchy (Experiments 4-7). The findings revealed a novel consequence of statistical learning in which new transitive associations between objects are implicitly inferred. PMID- 29787353 TI - Survey of roasted street-vended nuts in Sierra Leone for toxic metabolites of fungal origin. AB - Consumption of mycotoxin contaminated foodstuffs is common in regions where foods are not adequately controlled and routinely monitored, and this could have adverse effects on the health of consumers. In this study, 100 samples of roasted nuts (50 cashew nuts and 50 peanuts) vended within two cities of Sierra Leone were analysed for mycotoxins and other microbial metabolites by a LC-MS/MS method. The peanut samples contained detectable levels of 17 microbial metabolites, including aflatoxins B1, B2, G1 and G2 and alternariol, while none of these metabolites were found in the cashew samples. Aflatoxins (max: 5,729 MUg/kg; mean: 487.8 MUg/kg) and alternariol (3 MUg/kg) were found in 24% and 2% of the peanut samples, respectively. One-third of the aflatoxin-contaminated peanut samples contained aflatoxins at levels exceeding the total aflatoxin limit of 4 MUg/kg set by the European Union. Aflatoxin contamination of Sierra Leonean peanuts is high and requires urgent intervention to reduce consequent exposure. PMID- 29787354 TI - Optical Coherence Tomography of the Tympanic Membrane and Middle Ear: A Review. AB - Objective To evaluate the recent developments in optical coherence tomography (OCT) for tympanic membrane (TM) and middle ear (ME) imaging and to identify what further development is required for the technology to be integrated into common clinical use. Data Sources PubMed, Embase, Google Scholar, Scopus, and Web of Science. Review Methods A comprehensive literature search was performed for English language articles published from January 1966 to January 2018 with the keywords "tympanic membrane or middle ear,""optical coherence tomography," and "imaging." Conclusion Conventional imaging techniques cannot adequately resolve the microscale features of TM and ME, sometimes necessitating diagnostic exploratory surgery in challenging otologic pathology. As a high-resolution noninvasive imaging technique, OCT offers promise as a diagnostic aid for otologic conditions, such as otitis media, cholesteatoma, and conductive hearing loss. Using OCT vibrometry to image the nanoscale vibrations of the TM and ME as they conduct acoustic waves may detect the location of ossicular chain dysfunction and differentiate between stapes fixation and incus-stapes discontinuity. The capacity of OCT to image depth and thickness at high resolution allows 3-dimensional volumetric reconstruction of the ME and has potential use for reconstructive tympanoplasty planning and the follow-up of ossicular prostheses. Implications for Practice To achieve common clinical use beyond these initial discoveries, future in vivo imaging devices must feature low cost probe or endoscopic designs and faster imaging speeds and demonstrate superior diagnostic utility to computed tomography and magnetic resonance imaging. While such technology has been available for OCT, its translation requires focused development through a close collaboration between engineers and clinicians. PMID- 29787355 TI - Effect of Lavender cream with or without footbath on sleep quality and fatigue in pregnancy and postpartum: a randomized controlled trial. AB - BACKGROUND: Sleep disturbance and fatigue are frequent complaints during pregnancy and postpartum. We assessed the effectiveness of Lavender cream and footbath on sleep quality and fatigue in pregnancy and postpartum. METHODS: In this trial, 141 women with sleep disturbance at 25-28 weeks gestation were recruited from public health centers in Tabriz, Iran, from May 2013 until January 2014 and randomized into one of three groups receiving: Lavender and footbath, Lavender alone, or placebo cream. Sleep quality was assessed using the Pittsburgh sleep quality index at the 4th and 8th weeks after intervention and the 6th week postpartum. Fatigue was assessed with the multidimensional assessment of fatigue scale at the 6th week after intervention and the 6th week postpartum. Repeated measures ANOVA and ANCOVA were used. RESULTS: Compared with the placebo group, the global sleep quality score post-intervention in pregnancy and the postpartum were significantly lower in the Lavender and footbath and the Lavender cream only groups. Fatigue in both intervention groups was significantly improved only at the 6th week postpartum. No statistically significant differences were observed between the two intervention groups. CONCLUSION: Lavender cream with or without footbath may improve sleep quality in pregnancy and postpartum. PMID- 29787356 TI - Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update. AB - Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab based combination chemotherapy in patients with high-risk, early-stage, HER2 positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer guidelines . PMID- 29787358 TI - Targeting B-Cell Lymphoma 2: A Lethal Shortcut in Del(17p) Chronic Lymphocytic Leukemia. PMID- 29787357 TI - Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study. AB - Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point-development of symptomatic brain metastases at 24 months-was defined as one or a combination of key symptoms that suggest brain metastases-signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms-and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases ( P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low grade toxicity. PMID- 29787359 TI - Response-Adapted Therapy in Aggressive Lymphoma: Not Yet Ready for Clinical Care. PMID- 29787360 TI - Myotarsal flap - a versatile entity for lower eyelid reconstructions. AB - The purpose is to present a new surgical technique using myotarsal (MT) flap for reconstruction of small to subtotal full thickness defects - up to 8 mm in height - of lower eyelids, without needing concomitant supplementary procedures. MT flap consists of a 3 mm tarsal strip with attached levator complex. It does not have conjunctival lining or pedicle. Versatility of the flap extends to correction of mild to severe ptosis, and retraction of upper eyelids. This is a retrospective personal series of 163 patients, who underwent surgical reconstruction with MT flap overlaid with quilted skin graft (modified myotarsal flap) after excision of malignant tumours of lower eyelid. Surgery was on day case basis under LA. Patients were assessed for aesthetic and functional outcome, and complications. No patient had any complication. Assessment of outcome included corneal and ocular surface health and protection, eye closure, tear secretion, and lid contours. These were aesthetically and functionally satisfactory. Histology confirmed complete tumour clearance, and clinical diagnosis. There was no recurrence of tumour. An astounding, new, unique and original observation of the study is that cornea and ocular surface remained undamaged throughout, despite absence of conjunctival lining of MT flap. This goes against all current tenets of oculoplasty. Use of the modified MT flap is a safe, versatile, and effective procedure yielding satisfactory aesthetic and functional results for reconstruction of the lower eyelid. PMID- 29787361 TI - Sorption and degradation of neonicotinoid insecticides in tropical soils. AB - Neonicotinoids are the most widely applied class of insecticides in cocoa farming in Ghana. Despite the intensive application of these insecticides, knowledge of their fate in the Ghanaian and sub-Saharan African environment remains low. This study examined the behavior of neonicotinoids in soils from cocoa plantations in Ghana by estimating their sorption and degradation using established kinetic models and isotherms. Studies of sorption were conducted using the batch equilibrium method on imidacloprid, thiamethoxam, clothianidin, acetamiprid and thiacloprid, while degradation of imidacloprid, thiamethoxam and their respective deuterated counterparts was studied using models proposed by the European forum for coordination of pesticide fate and their use (FOCUS). Analytes were extracted using the quick, easy, cheap, effective, rugged and safe (QuEChERS) procedure and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Average recoveries were high (>= 85%) for all analytes. The findings from the study suggest that neonicotinoid insecticides may be persistent in the soils studied based on estimated half-lives > 150 days. The study also revealed generally low sorption coefficients for neonicotinoids in soils, largely influenced by soil organic carbon. PMID- 29787362 TI - J Pouch: Imaging Findings, Surgical Variations, Natural History, and Common Complications. AB - Ileal pouch-anal anastomosis, or J pouch, surgery has become the procedure of choice for treatment of medically refractory ulcerative colitis and familial adenomatous polyposis. Overall, this operation is associated with a low rate of postoperative morbidity and good long-term function. However, when complications develop, there is a heavy reliance on imaging to facilitate an accurate diagnosis. Reported postoperative complication rates range from 5% to 35%. Complications generally can be categorized as structural, inflammatory, or neoplastic conditions. Structural complications include leaks, strictures, afferent and efferent limb syndromes, and pouch prolapse. Inflammatory conditions include cuffitis, pouchitis, and Crohn disease of the pouch. In addition, a variety of neoplastic conditions can develop in the pouch. Overall, pouchitis and leaks are the most common complications, occurring in up to 50% and 20% of individuals, respectively. Many imaging modalities are used to evaluate the J pouch and associated postoperative complications. The indications and various surgical techniques for J pouch surgery, normal postoperative appearance of the pouch, and most common associated complications are reviewed. In addition, the various imaging findings associated with J pouch surgery are described and illustrated. The radiologist's familiarity with the potential complications of the pouch can facilitate appropriate imaging, hasten an accurate diagnosis, and aid in rendering proper management. (c)RSNA, 2018. PMID- 29787363 TI - Nonepithelial Neoplasms of the Pancreas, Part 2: Malignant Tumors and Tumors of Uncertain Malignant Potential From the Radiologic Pathology Archives. AB - Almost all neoplasms of the pancreas are derived from pancreatic epithelial components, including the most common pancreatic mass, primary pancreatic ductal adenocarcinoma (PDAC). Nonepithelial neoplasms comprise only 1%-2% of all pancreatic neoplasms. Although some may arise directly from intrapancreatic elements, many originate from mesenchymal, hematopoietic, or neural elements in the retroperitoneal peripancreatic space and grow into the pancreas. Once these tumors reach a certain size, it can be challenging to identify their origin. Because these manifest at imaging as intrapancreatic masses, awareness of the existence and characteristic features of these nonepithelial neoplasms is crucial for the practicing radiologist in differentiating these tumors from primary epithelial pancreatic tumors, an important distinction given the vastly different management and prognosis. In part 1 of this article, the authors reviewed benign nonepithelial neoplasms of the pancreas. This article focuses on malignant nonepithelial neoplasms and those of uncertain malignant potential that can be seen in the pancreas. The most common malignant or potentially malignant nonepithelial pancreatic tumors are of mesenchymal origin and include soft-tissue sarcomas, solitary fibrous tumor, and inflammatory myofibroblastic tumor. These tumors commonly manifest as large heterogeneous masses, often containing areas of necrosis and hemorrhage. The clinical features associated with these tumors and the imaging characteristics including enhancement patterns and the presence of fat or calcification help distinguish these tumors from PDAC. Hematopoietic tumors, including lymphoma and extramedullary plasmacytoma, can manifest as isolated pancreatic involvement or secondarily involve the pancreas as widespread disease. Hyperenhancing paragangliomas or hypervascular metastatic disease can mimic primary pancreatic neuroendocrine tumors or vascular anomalies. PMID- 29787364 TI - Effect of respiratory Achromobacter spp. infection on pulmonary function in patients with cystic fibrosis. AB - PURPOSE: Cystic fibrosis (CF) patients are susceptible to infection with Achromobacter spp., although its clinical significance remains controversial. The aim of this study was to investigate the clinical impact of infection with Achromobacter spp. in CF patients. METHODS: CF outpatients with multiple sputum cultures and follow-up lung function tests were assigned to the case group (infected with Achromobacter spp.) or the control group (never infected with Achromobacter spp.) according to the isolation of Achromobacter spp. The Achromobacter spp. group included two subgroups, taking into consideration whether the isolation of Achromobacter spp. was intermittent or chronic. Baseline lung function tests and longitudinal behaviour were examined in relation to Achromobacter spp. status. RESULTS: A total of 190 CF patients were treated from January 2003 to December 2015 in the CF unit and 21 (11 %) had at least one positive culture for Achromobacter spp. Of these, 11/21 (52.4 %) patients were chronically infected with Achromobacter spp. An analysis of changes during follow up showed the annual rate of FEV1 decline: -2.3+/-1.6 % in the Achromobacter spp. group compared to -1.1+/-0.9 % (P=0.02) in the control group. The chronically infected group also had a significantly greater decline in FEV1 compared to the control group (-2.9+/-1.9 vs -1.1+/-0.9; P=0.04). The mean number of annual pulmonary exacerbations during the study period was significantly higher in the case group (1.9+/-0.9 vs 1.1+/-0.8; P=0.03). CONCLUSIONS: The Achromobacter spp. status in CF shows a trend towards more severe airflow obstruction and an association with accelerated decline in lung function parameters. PMID- 29787365 TI - KPC-2 producing ST101 Klebsiella pneumoniae from bloodstream infection in India. AB - This study characterizes KPC-2 producing Klebsiella pneumoniae belonging to ST101. Whole genome sequencing using the Ion Torrent PGM platform with 400 bp chemistry was performed. blaKPC-2 was found on an IncFIIK plasmid associated with ISKpn6 and ISKpn7 without Tn4401. This is the first report of KPC-2 K. pneumoniae from bacteremia in India. The isolate also coded for other resistance genes such as aadA1, aadA2, armA, aac(3)-Ild, aac(6')-Ild for aminoglycoside; blaSHV-11, blaTEM-1B, blaOXA-9, for beta-lactams and aac(6')-Ild, oqxA, oqxB, qnrB1 for fluoroquinolones. It belonged to the K17 capsular type. India is endemic to New Delhi metallo-beta-lactamase and OXA48-like carbapenemases and K. pneumoniae carbapenemase (KPC) is seldom reported. With high rates of carbapenem resistance, emergence of KPC in India will challenge patient management. The isolate was susceptible to colistin. The patient had a fatal outcome. PMID- 29787366 TI - Parasympathetic activity increases with digital microvascular damage and vascular endothelial growth factor in systemic sclerosis. AB - OBJECTIVES: The imbalance between angiogenic and angiostatic factors with derangement of the microvasculature are hallmarks of systemic sclerosis (SSc). Raynaud's phenomenon in SSc probably is due to the impaired neuroendothelial control mechanisms between vasoconstriction and vasodilatation. The aim of this study is to evaluate autonomic nervous system function using heart rate variability (HRV) analysis and to correlate with vascular endothelial growth factor (VEGF). METHODS: Twenty-seven SSc patients were enrolled. HRV was measured and markers of global sympathetic and parasympathetic system, respectively standard deviation of normal-to-normal RR intervals (SDNN) and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) were evaluated. Serum VEGF levels and nailfold videocapillaroscopy (NVC) were performed. RESULTS: A linear positive correlation was observed between RMSSD and VEGF (p<0.01, r=0.55), and RMSSD and disease duration (p< 0.01, r=0.54). The RMSSD median value was significantly increased (p< 0.05) with NVC damage progression. The RMSSD median value was significantly (p<0.05) higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [44 (39.4 60.2) vs 24.6 (23-37.1)]. CONCLUSIONS: In our study parasympathetic modulation increases in relation to VEGF. When microcirculation is modified with capillaroscopic pattern progression and DUs, autonomic system seems to stimulate vasodilatation trough parasympathetic system. We can conclude that parasympathetic activity increases with digital microvascular damage and promotes VEGF release. PMID- 29787367 TI - Case - Ex-vivo aneurysm resection, autotransplantation, and aorto-renal bypass in a solitary kidney with fibromuscular dysplasia. PMID- 29787368 TI - Contemporary surgical outcomes of venous tumour thrombectomy managed with intraoperative Doppler ultrasound for kidney cancer. AB - INTRODUCTION: Radical nephrectomy (RN) with venous tumour thrombectomy (VTT) carries a significant morbidity and mortality risk. Examination of a contemporary single-institution series permits the development of a management algorithm and an audit its results. We report outcomes following the use of intraoperative colour Doppler ultrasound and our surgical pathway. METHODS: We retrospectively reviewed the records of all patients who underwent RN with VTT for kidney cancer between January 1, 2013 and October 1, 2016. Surgical complications, postoperative complications (Clavien-Dindo classification >=3), 90-day readmission rates, and outcomes are reported. Multivariate linear regression, logistic regression, and Cox proportional hazard modelling were used to identify associations. RESULTS: Fifty-eight patients underwent RN with VTT. Of these, 26 (45%) patients had Mayo Clinic level III or IV thrombus and nineteen required venovenous/cardiopulmonary bypass. Three patients required patch grafting. The median length of hospital stay was eight days and there were 20 major complications. The 30-day readmission rate was 21% and the 90-day mortality rate was 8.9%. In multivariate analysis, low serum albumin and age-adjusted Charlson comorbidity score predicted length of stay. Increased intraoperative blood loss was significantly associated with increasing body mass index, serum creatinine, tumour thrombus level, and a history of significant weight loss >9.1kg. Low serum hematocrit predicted 90-day mortality. CONCLUSIONS: Intraoperative colour Doppler ultrasound is a useful tool and can facilitate caval preservation. Caval grafting can be avoided in most cases. Venovenous bypass can be avoided in many level III cases. Early therapeutic anticoagulation should be instituted with caution. PMID- 29787369 TI - Images - Well-differentiated papillary mesothelioma of the tunica vaginalis. PMID- 29787371 TI - The impact of targeted therapy on healthcare resource use in patients with metastatic renal cell carcinoma: The University of Sherbrooke experience. AB - INTRODUCTION: We assessed the impact of targeted therapies on healthcare resource use and compared treatment regimens used in patients diagnosed with metastatic renal cell carcinoma (mRCC). METHODS: Clinicopathological and administrative data of patients with mRCC from our institution were retrospectively collected from January 2000 to August 2014. Patients were divided into two groups based on the use of targeted therapies. Healthcare resource use (HCRU) data included non scheduled total number of hospitalizations, total days hospitalized, emergency department visits, and healthcare professional consultations. Each variable was presented with absolute and relative values (i.e., per month of survival). Statistics relied on the use of t-student and Chi-square tests. RESULTS: Ninety nine patients were included in the study; 60 were treated with targeted therapy. There were no statistically significant differences between the two groups for demographic features and clinicopathological stage. HCRU analysis revealed an absolute increase in the median number of healthcare consultants (6 vs. 4; p<0.01) and emergency department visits (1 vs. 0; p=0.02) for the targeted therapy group. However, analysis per month of survival showed the targeted therapy group had fewer consultants (0.33 vs. 0.40; p=0.04) and hospitalizations (0.09 vs. 0.13; p=0.03) than their counterpart. Population size, non randomization, treatment selection bias, and heterogeneity were the main limitations of this study. CONCLUSIONS: Monthly use of HCRU is lower in mRCC patients treated with targeted therapies. However, because of a greater overall survival, their absolute total HCRU will be higher than those not exposed to targeted agents. PMID- 29787370 TI - How long do we have to treat overactive bladder syndrome (OAB)? A questionnaire survey of Canadian urologists and gynecologists. AB - INTRODUCTION: Overactive bladder syndrome (OAB) is a highly prevalent and costly condition worldwide with negative impact on health-related quality of life. Although many guidelines exist and anticholinergics are considered to be the mainstay of pharmacological treatment, data are lacking regarding optimal treatment duration. Therefore, the aim of this study was to determine practice patterns of Canadian urologists and gynecologists regarding duration of OAB pharmacotherapy. METHODS: A 14-question survey was designed and survey links (English and French) were sent by email to all practicing urologists and gynecologists registered with the Canadian Urological Association and the Society of Obstetricians and Gynecologists of Canada via the associations' email lists. The SurveyMonkey website served as platform where responses were collected and stored. RESULTS: A total of 301 physicians completed the questionnaire; 250 respondents (83%) prescribe anticholinergics or beta-3-adrenoceptor agonist (mirabegron) in their practice, and 202 (81%) start patient treatment with the lowest recommended medication dose. One hundred and twelve respondents (45% of those who prescribe OAB medications) classified OAB pharmacotherapy as a lifelong management strategy, whereas 130 (52% of those who prescribe OAB medications) think that OAB pharmacotherapy should be administered for a defined time period. Six-month and one-year time periods of drug treatments are the most commonly chosen answers given by physicians who treat their patients for a defined duration. CONCLUSION: There is general agreement among Canadian urologists and gynecologists that OAB treatment should be started with the lowest recommended medication dose. A slim majority of respondents think that OAB pharmacotherapy should be administered for a defined duration. PMID- 29787372 TI - Current use of medical expulsive therapy among endourologists. AB - INTRODUCTION: We aimed to characterize current practice patterns among endourologists on medical expulsive therapy (MET) for treatment of ureteral calculi. METHODS: An online survey was administered to Endourological Society members. Respondents' MET usage, index case management, and awareness of recent guidelines and literature were compared based on international status, practice setting, interval since training, and endourological fellowship training. RESULTS: Of the 237 complete responses, 65% were international, 61% were academic, 66% had >10 years in practice, and 71% were endourology fellowship trained. MET was used by 88%, with no differences between international, academic, practice length, and fellowship-trained groups. MET was used more frequently for <8 mm and distal stones and more U.S.-based respondents reported use for proximal/midureteral stones (68% vs 43%; p<0.001). For the index patient, 70% preferred MET as the initial approach and respondents <10 years from training were more likely to choose MET (82% vs. 64%; p=0.006). While 82% of respondents were aware of the SUSPEND trial, 70% reported that it had not altered their use of MET. Current American Urological Association (AUA) guideline awareness was 90%. Mean MET prescription length was 19.9+/-10.3 days, and was statistically significantly longer for respondents who were U.S.-based, academic and <10 years from training. CONCLUSIONS: MET is the preferred approach for patients with ureteral calculi <10 mm among endourologists despite conflicting data in the literature. While current AUA practice guidelines are followed by the majority of respondents, our survey suggests MET is being used more liberally than the guideline criteria, specifically in proximal and midureteral stones. PMID- 29787373 TI - Gynecological organ involvement at robot-assisted radical cystectomy in females: Is anterior exenteration necessary? AB - INTRODUCTION: We aimed to investigate patient and disease variables associated with gynecological organ invasion in females with bladder cancer at the time of robot-assisted radical cystectomy (RARC). METHODS: We conducted a retrospective review of female patients who underwent robot-assisted anterior pelvic exenteration (RAAE) between 2005 and 2016. Patients were divided into two groups: those with gynecological organ involvement at RAAE and those without. Data were reviewed for perioperative and pathological outcomes. Kaplan-Meier method was used to depict survival outcomes. Multivariable stepwise regression analysis was performed to identify predictors of gynecological organ involvement. RESULTS: A total of 118 female patients were identified; 17 (14%) showed evidence of gynecological organ invasion at RAAE. Patients with gynecological organ invasion had more lymphovascular invasion at transurethral resection of bladder tumour (TURBT) (82% vs. 46%; p=0.006), trigonal tumours at TURBT (59% vs. 18%; p=0.001), multifocal disease (65% vs. 33%; p=0.01), pN+ (71% vs. 22%; p<0.001), positive surgical margins (24% vs. 4%; p=0.02), and they less commonly demonstrated pure urothelial carcinoma at TURBT (18% vs. 66%; p<0.001). On multivariate analysis, significant predictors of gynecological organ invasion were pN positive disease (odds ratio [OR] 6.48; 95% confidence interval [CI] 1.64-25.51; p=0.008), trigonal tumour location (OR 5.72; 95% CI 1.39-23.61; p=0.02), and presence of variant histology (OR18.52; 95% CI 3.32-103.4; p=0.001). CONCLUSIONS: Patients with trigonal tumours, variant histology, and nodal involvement are more likely to have gynecological organs invasion at RAAE. This information may help improve counselling of patients and better identify candidates for gynecological organ sparing cystectomy. PMID- 29787374 TI - Evaluating the impact of the genitourinary multidisciplinary tumour board: Should every cancer patient be discussed as standard of care? AB - INTRODUCTION: We sought to prospectively evaluate the effectiveness of the multidisciplinary tumour board (MTB) on altering treatment plans for genitourinary (GU) cancer patients. METHODS: All GU cancer patients seen at our tertiary care hospital are discussed at MTB. We prospectively collected data on adult patients discussed over a continuous, 20-month period. Physicians completed a survey prior to MTB to document their opinion on the likelihood of change in their patient's treatment plan. Logistic regression was used to asses for factors associated with a change by the MTB, including patient age or sex, malignancy type, the predicted treatment plan, and the provider's years of experience or fellowship training. RESULTS: A total of 321 cancer patients were included. Patients were primarily male (84.4%) with a median age of 67 (range 20-92) years old. Prostate (38.9%), bladder (31.8%), and kidney cancer (19.6%) were the most common malignancies discussed. A change in management plan following MTB was observed in 57 (17.8%) patients. The physician predicted a likely change in six (10.5%) of these patients. Multivariate logistic regression did not determine physician prediction to be associated with treatment plan change, and the only significant variable identified was a plan to discuss multiple treatment options with a patient (odds ratio 2.46; 95% confidence interval 1.09-9.54). CONCLUSIONS: Routine discussion of all urologic oncology cases at MTB led to a change in treatment plan in 17.8% of patients. Physicians cannot reliably predict which patients have their treatment plan altered. Selectively choosing patients to be presented likely undervalues the impact of a multidisciplinary approach to care. PMID- 29787375 TI - Transperitoneal laparoscopic heminephroureterectomy in pediatric population: A single-centre experience using a sealing device. AB - INTRODUCTION: We sought to report the outcomes of transperitoneal laparoscopic heminephroureterectomy (LHNU) in pediatric population and to describe the technical details of this minimally invasive surgery. METHODS: Seventeen pediatric patients (18 renal units), who had consecutive transperitoneal LHNU in our department between January 2012 and July 2017 were included in the study. In all patients, diagnostic cystoscopy and retrograde pyelography were carried out immediately before the operation. A catheter was inserted in the unaffected ureter and fixed. LHNU with a transperitoneal approach was carried out in all patients with the aid of LigaSure(r). After removal of the specimen, the intervention was finalized with the insertion of a drain. All intraoperative and postoperative data of the patients were recorded prospectively. RESULTS: The average age of the patients was 55.9+/-35.8 months (range 8-121). The average duration of the operations was 121.7+/-24.0 minutes (range 100-200). The average hospitalization time was 1.6+/-0.4 days (range 1-2). No intraoperative complication occurred in our patients. The average followup period was 29.1+/ 13.4 months (range 4-48). During the followup period, no complications were observed except one patient who had pyelonephritis within the first month of surgery. CONCLUSIONS: Transperitoneal LHNU is a minimally invasive method that can be used safely in pediatric patients. Using a standardized technique during the procedure is critical to increase the success and decrease the complication rates. PMID- 29787376 TI - Symptom assessment to guide treatment selection and determine progression in metastatic castration-resistant prostate cancer: Expert opinion and review of the evidence. AB - Multiple new agents to treat metastatic castration-resistant prostate cancer (mCRPC) have become available in recent years; however, the appropriate timing and sequencing of these agents have yet to be elucidated. Until accurate biomarkers become available to allow more focused therapeutic targeting for this population, treatment selection for men with mCRPC will continue to be driven largely by close assessment of patient-related factors and symptoms. Pain, as the predominant symptom of mCRPC, is often the focus when assessing progression and the need for a change in treatment. A myriad of other symptoms, including fatigue, impact on activities of daily living, sleep, and lower urinary tract symptoms, also affect men with mCRPC, and assessment of the composite of these symptoms provides an earlier signal for the need to adjust treatment. A number of tools are available for assessing symptoms in patients with advanced prostate cancer, but they are not used routinely used, given their complexity and length. A new simplified questionnaire is proposed for the assessment of symptoms, beyond pain, to inform treatment decisions for men with mCRPC. PMID- 29787377 TI - The effects of inulin and fructo-oligosaccharide on the probiotic properties of Lactobacillus spp. isolated from human milk. PMID- 29787378 TI - Larval hemolymph of rhinoceros beetle, Allomyrina dichotoma, enhances insulin secretion through ATF3 gene expression in INS-1 pancreatic beta-cells. PMID- 29787379 TI - Selection of bone dosimetry models for application in Monte Carlo simulations to provide CT scanner-specific organ dose coefficients. AB - This is the second paper arising from a project concerning the application of Monte Carlo simulations to provide scanner-specific organ dose coefficients for modern CT scanners. The present focus is centred on the bone dosimetry models that have been developed. Simulations have been performed in photon only transport mode, with the assumption of electron equilibrium. This approximation breaks down for doses to active marrow and endosteum since the target cells are localised within tens of micrometre from bone tissue and dose enhancement functions are necessary to correct for the additional dose from photoelectric electrons created in adjacent material. The dose enhancement models used previously in publications NRPB-SR250 (Jones and Shrimpton 1993 Software Report NRPB-SR250, National Radiological Protection Board, Chilton, UK) and ORNL-TM8381 (Cristy and Eckerman 1987 Technical Report Oak Ridge National Laboratory, Oak Ridge, TN) have been implemented and compared with the contemporary approaches of Johnson et al (2011 Phys. Med. Biol. 56 2347-65) and ICRP Publication 116 (ICRP 2010 Ann. ICRP 40 1-257) that are being adopted in the present project. In addition, the calculation of dose to endosteum in the medullary cavity is reviewed and updated using electron mode simulations. For the purposes of quality assurance and comparison, the various dose enhancement functions have been applied in relation to the NRPB18+DJ and HPA18+ stylised hermaphrodite phantoms and also the adult male and female voxel phantoms recommended in ICRP Publication 110 (ICRP 2009 Ann. ICRP 39 1-165), for exposure from three CT scanners modelled previously. Contemporary results for standard examinations on the head and trunk calculated for these latter phantoms demonstrate moderate increases (modal value +18%) in active marrow dose coefficients relative to values derived from data published in NRPB-SR250. A similar analysis in relation to endosteum dose coefficients shows larger reductions (modal value -46%), owing at least in part to changes in assumed location of the target cells. Even larger changes are apparent for both of these dose coefficients in relation to examination of the upper legs (-39% and -94%, respectively). However, resultant changes in any values of effective dose will be less owing to the low weighting factors applied for these tissues. PMID- 29787380 TI - An image reconstruction method with a locally adaptive gating scheme for PET data. AB - In conventional gating approaches for positron emission tomography (PET), a single number of gates is predetermined for the whole field of view (FOV) regardless of spatially variant motion blurring effects, which compromises image quality by under-gating regions of large motion and over-gating static regions. To achieve the best resolution-noise trade-off for the whole FOV, we proposed a new approach that incorporates a spatially variant number of gates into gated image reconstruction. The first step was to estimate the motion amplitude of each spatial location. A preliminary set of gated image reconstructions was generated from the PET data. The spatially variant motion amplitudes were approximated based on the registration of 2D maximum intensity projections of the gated reconstructions as well as prior knowledge. Second, the spatially varying motion amplitudes were used to determine the optimal number of gates for each region. Finally, the adaptive gating image reconstruction algorithm that incorporates a gating transform function to model the spatially variant number of gates was applied to generate adaptively gated 4D images. Scans from large FOV systems were simulated using actual multi-bed patient data from a clinical scanner for evaluation purposes. Images reconstructed with the conventional gating scheme as well as static reconstruction were obtained for comparison with the results obtained using our new method. In areas with lower estimated motion amplitudes (such as the spine), the reconstructed images using the new approach showed reduced noise compared to images with conventional gated reconstructions and comparable quality with non-gated images. In areas with large estimated motion amplitudes, such as in the lung and liver, contrast and resolution of images using the new method and conventional gated-reconstructions were comparable, and both were higher than those of non-gated images. The results indicate that using a locally adaptive number of gates based on respiratory motion amplitude instead of a fixed number of gates can improve the statistics of gated PET images by optimizing the local noise-resolution trade-off. PMID- 29787381 TI - Multi atlas based segmentation: should we prefer the best atlas group over the group of best atlases? AB - Multi atlas based segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases. Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split into two groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle selection, where atlases are chosen by the highest dice similarity coefficient (DSC) with the target, was performed. This was compared to oracle group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, convolutional neural networks were designed to predict the best group of atlases. The results were also compared with the selection strategy based on normalized mutual information (NMI). Oracle group was proven to be significantly better than classic oracle selection (p < 10-5). Atlas group selection led to a median +/- interquartile DSC of 0.740 +/- 0.084, 0.718 +/ 0.086 and 0.670 +/- 0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676 +/- 0.113, 0.632 +/- 0.104 and 0.606 +/- 0.118 (p < 0.001) as well as classic oracle selection. The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS. PMID- 29787382 TI - Machine learning-based dual-energy CT parametric mapping. AB - The aim is to develop and evaluate machine learning methods for generating quantitative parametric maps of effective atomic number (Zeff), relative electron density (rho e), mean excitation energy (I x ), and relative stopping power (RSP) from clinical dual-energy CT data. The maps could be used for material identification and radiation dose calculation. Machine learning methods of historical centroid (HC), random forest (RF), and artificial neural networks (ANN) were used to learn the relationship between dual-energy CT input data and ideal output parametric maps calculated for phantoms from the known compositions of 13 tissue substitutes. After training and model selection steps, the machine learning predictors were used to generate parametric maps from independent phantom and patient input data. Precision and accuracy were evaluated using the ideal maps. This process was repeated for a range of exposure doses, and performance was compared to that of the clinically-used dual-energy, physics based method which served as the reference. The machine learning methods generated more accurate and precise parametric maps than those obtained using the reference method. Their performance advantage was particularly evident when using data from the lowest exposure, one-fifth of a typical clinical abdomen CT acquisition. The RF method achieved the greatest accuracy. In comparison, the ANN method was only 1% less accurate but had much better computational efficiency than RF, being able to produce parametric maps in 15 s. Machine learning methods outperformed the reference method in terms of accuracy and noise tolerance when generating parametric maps, encouraging further exploration of the techniques. Among the methods we evaluated, ANN is the most suitable for clinical use due to its combination of accuracy, excellent low-noise performance, and computational efficiency. PMID- 29787383 TI - Deep learning for undersampled MRI reconstruction. AB - This paper presents a deep learning method for faster magnetic resonance imaging (MRI) by reducing k-space data with sub-Nyquist sampling strategies and provides a rationale for why the proposed approach works well. Uniform subsampling is used in the time-consuming phase-encoding direction to capture high-resolution image information, while permitting the image-folding problem dictated by the Poisson summation formula. To deal with the localization uncertainty due to image folding, a small number of low-frequency k-space data are added. Training the deep learning net involves input and output images that are pairs of the Fourier transforms of the subsampled and fully sampled k-space data. Our experiments show the remarkable performance of the proposed method; only 29[Formula: see text] of the k-space data can generate images of high quality as effectively as standard MRI reconstruction with the fully sampled data. PMID- 29787384 TI - Automatic centerline extraction of cerebrovascular in 4D CTA based on tubular features. AB - Vascular centerlines have crucial significance in reconstruction, registration, segmentation and vascular parameter analysis. The extraction of vessel structures remains a difficult problem in the completeness and continuity of results. In this paper, we present a novel method to extract cerebrovascular centerlines from four-dimensional computed tomography angiography images. Tubular features and vascular directions are used to extract initial centerlines, and the offset correction is introduced in the vascular orthogonal plane. In addition, we also present a post-processing method to connect interruptions of centerlines. We perform a quantitative validation using clinical images and public data sets of MRA brain images. Our experimental results demonstrate that the proposed algorithm not only shows higher accuracy in complicated vessel structures, but also outperforms previous approaches in terms of high validity and universality. PMID- 29787385 TI - A Systematic Review and Narrative Synthesis to Explore the Effectiveness of Exercise-Based Interventions in Improving Fatigue, Dyspnea, and Depression in Lung Cancer Survivors. AB - BACKGROUND: Lung cancer survival rates are increasing; however, lung cancer survivors' mental and physical well-being can suffer from experiencing symptoms of fatigue, dyspnea, and depression. Exercise can improve these symptoms. However, no studies have examined the effects of different exercise interventions on these symptoms. OBJECTIVE: This review aims to examine the evidence on the effects of exercise interventions on fatigue, dyspnea, and depression in lung cancer survivors. METHODS: PRISMA guidelines were followed. CINAHL, MEDLINE, EMBASE, and Cochrane databases were searched between 2000 and May 2017. Gray literature was searched. All identified studies were screened for inclusion. Quantitative data were narratively synthesized. RESULTS: From 852 records retrieved and screened, 10 full-text articles were included. Seven studies had a high risk of bias, 2 had an unclear risk, and 1 study had a low risk, limiting the robustness of findings. Exercise interventions included pulmonary rehabilitation, aerobic exercise, resistance training, exercise and balance programs, and medical qigong. Six studies reported statistically significant reductions in fatigue; 2 reported significant improvements in dyspnea, and one a significant reduction in depression postintervention. CONCLUSIONS: Exercise interventions may be effective and are unlikely to cause harm for lung cancer survivors. However, evidence quality is limited. More rigorous study designs are required to provide guidance about which interventions may help lung cancer survivors self-manage these symptoms. IMPLICATIONS FOR PRACTICE: Health professionals should provide comprehensive, customized exercise screening and treatment plans to lung cancer survivors to complement their lifestyle needs and ensure appropriate recommendations aimed at improving symptom control are communicated to them. PMID- 29787386 TI - Comparison of Tracheal Intubation Conditions in Operating Room and Intensive Care Unit: A Prospective, Observational Study. AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Tracheal intubation is a common intervention in the operating room and in the intensive care unit. The authors hypothesized that tracheal intubation using direct laryngoscopy would be associated with worse intubation conditions and more complications in the intensive care unit compared with the operating room. METHODS: The authors prospectively evaluated during 33 months patients who were tracheally intubated with direct laryngoscopy in the operating room, and subsequently in the intensive care unit (within a 1-month time frame). The primary outcome was to compare the difference in glottic visualization using the modified Cormack-Lehane grade between intubations performed on the same patient in an intensive care unit and previously in an operating room. Secondary outcomes were to compare first-time success rate, technical difficulty (number of attempts, operator-reported difficulty, need for adjuncts), and the incidence of complications. RESULTS: A total of 208 patients met inclusion criteria. Tracheal intubations in the intensive care unit were associated with worse glottic visualization (Cormack-Lehane grade I/IIa/IIb/III/IV: 116/24/47/19/2) compared with the operating room (Cormack-Lehane grade I/IIa/IIb/III/IV: 159/21/16/12/0; P < 0.001). First-time intubation success rate was lower in the intensive care unit (185/208; 89%) compared with the operating room (201/208; 97%; P = 0.002). Tracheal intubations in the intensive care unit had an increased incidence of moderate and difficult intubation (33/208 [16%] vs. 18/208 [9%]; P < 0.001), and need for adjuncts to direct laryngoscopy (40/208 [19%] vs. 21/208 [10%]; P = 0.002), compared with the operating room. Complications were more common during tracheal intubations in the intensive care unit (76/208; 37%) compared with the operating room (13/208; 6%; P < 0.001). CONCLUSIONS: Compared with the operating room, tracheal intubations in the intensive care unit were associated with worse intubation conditions and an increase of complications. PMID- 29787387 TI - Targeting Microglia: A New Avenue for Anesthesia Neuroprotection after Brain Injury? PMID- 29787388 TI - Dying as a Pathway to Death in Sepsis. PMID- 29787390 TI - Genitourinary Syndrome of Menopause. AB - Genitourinary syndrome of menopause (GSM) describes a collection of exam findings and bothersome symptoms associated with estrogen deficiency involving changes to the labia, introitus, clitoris, vagina, urethra, and bladder. Vulvovaginal atrophy is a component of GSM. GSM is a highly prevalent medical condition with adverse effects on the health and quality of life of midlife women. There are many effective treatment options, including nonhormonal lubricants and moisturizers, physical therapy, low-dose vaginal estrogen therapy, vaginal dehydroepiandrosterone, and oral ospemifene. Despite the availability of safe and effective therapies, GSM often remains unrecognized and untreated. PMID- 29787389 TI - Liposomal Bupivacaine Does Not Reduce Inpatient Opioid Prescription or Related Complications after Knee Arthroplasty: A Database Analysis. AB - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS MANUSCRIPT TELLS US THAT IS NEW: BACKGROUND:: Although some trials suggest benefits of liposomal bupivacaine, data on real-world use and effectiveness is lacking. This study analyzed the impact of liposomal bupivacaine use (regardless of administration route) on inpatient opioid prescription, resource utilization, and opioid-related complications among patients undergoing total knee arthroplasties with a peripheral nerve block. It was hypothesized that liposomal bupivacaine has limited clinical influence on the studied outcomes. METHODS: The study included data on 88,830 total knee arthroplasties performed with a peripheral nerve block (Premier Healthcare Database 2013 to 2016). Multilevel multivariable regressions measured associations between use of liposomal bupivacaine and (1) inpatient opioid prescription (extracted from billing) and (2) length of stay, cost of hospitalization, as well as opioid-related complications. To reflect the difference between statistical and clinical significance, a relative change of 15% in outcomes was assumed to be clinically important. RESULTS: Overall, liposomal bupivacaine was used in 21.2% (n = 18,817) of patients that underwent a total knee arthroplasty with a peripheral nerve block. Liposomal bupivacaine use was not associated with a clinically meaningful reduction in inpatient opioid prescription (group median, 253 mg of oral morphine equivalents, adjusted effect 9.3% CI -11.1%, -7.5%; P < 0.0001) and length of stay (group median, 3 days, adjusted effect -8.8% CI -10.1%, -7.5%; P < 0.0001) with no effect on cost of hospitalization. Most importantly, liposomal bupivacaine use was not associated with decreased odds for opioid-related complications. CONCLUSIONS: Liposomal bupivacaine was not associated with a clinically relevant improvement in inpatient opioid prescription, resource utilization, or opioid-related complications in patients who received modern pain management including a peripheral nerve block. PMID- 29787391 TI - Comparing wavefront-optimized, wavefront-guided and topography-guided laser vision correction: clinical outcomes using an objective decision tree. AB - PURPOSE OF REVIEW: This review is intended to update and educate the reader on the currently available options for laser vision correction, more specifically, laser-assisted in-situ keratomileusis (LASIK). In addition, some related clinical outcomes data from over 1000 cases performed over a 1-year are presented to highlight some differences between the various treatment profiles currently available including the rapidity of visual recovery. The cases in question were performed on the basis of a decision tree to segregate patients on the basis of anatomical, topographic and aberrometry findings; the decision tree was formulated based on the data available in some of the reviewed articles. RECENT FINDINGS: Numerous recent studies reported in the literature provide data related to the risks and benefits of LASIK; alternatives to a laser refractive procedure are also discussed. The results from these studies have been used to prepare a decision tree to assist the surgeon in choosing the best option for the patient based on the data from several standard preoperative diagnostic tests. SUMMARY: The data presented here should aid surgeons in understanding the effects of currently available LASIK treatment profiles. Surgeons should also be able to appreciate how the findings were used to create a decision tree to help choose the most appropriate treatment profile for patients. Finally, the retrospective evaluation of clinical outcomes based on the decision tree should provide surgeons with a realistic expectation for their own outcomes should they adopt such a decision tree in their own practice. PMID- 29787392 TI - Aortic Dissection: True or False? PMID- 29787394 TI - New developments in the genetic diagnosis of short stature. AB - PURPOSE OF REVIEW: Genome-wide approaches including genome-wide association studies as well as exome and genome sequencing represent powerful new approaches that have improved our ability to identify genetic causes of human disorders. The purpose of this review is to describe recent advances in the genetic causes of short stature. RECENT FINDINGS: In addition to SHOX deficiency which is one of the most common causes of isolated short stature, PAPPA2, ACAN, NPPC, NPR2, PTPN11 (and other rasopathies), FBN1, IHH and BMP2 have been identified in isolated growth disorders with or without other mild skeletal findings. In addition, novel genetic causes of syndromic short stature have been discovered, including pathogenic variants in BRCA1, DONSON, AMMECR1, NFIX, SLC25A24, and FN1. SUMMARY: Isolated growth disorders are often monogenic. Specific genetic causes typically have specific biochemical and/or phenotype characteristics which are diagnostically helpful. Identification of additional subjects with a specific genetic cause of short stature often leads to a broadening of the known clinical spectrum for that condition. The identification of novel genetic causes of short stature has provided important insights into the underlying molecular mechanisms of growth failure. PMID- 29787393 TI - Recanalization of Chronic Occlusion of the Middle Cerebral Artery With Tissue Plasminogen Activator Treatment: A Case Report. AB - OBJECTIVES: Patients with chronic proximal middle cerebral artery (MCA) occlusion do not present with severe symptoms, but early recanalization of acute occlusion is associated with high morbidity and mortality. Tissue plasminogen activator (tPA) is a recombinant thrombolytic agent approved for treating ischemic stroke, although only a few cases of tPA administration in chronic MCA occlusion have yielded positive results. METHODS: A 71-year-old patient had a history of right MCA territorial infarction with the occlusion occurring 12 years ago (November 2005). Although the patient was treated with antiplatelet agents, MCA recanalization was not achieved. The patient was referred to our hospital again (January 2017) for newly discovered symptoms. We immediately administered tPA because the patient presented 2 hours after onset of symptoms. RESULTS: Neurological symptoms resolved within 24 hours of treatment, and magnetic resonance angiography confirmed recanalization of the right MCA territorial lesion. No neurological abnormalities were observed during the 12-week follow-up. CONCLUSIONS: At present, tPA is the only approved treatment for acute ischemic stroke, although it presents a limited time frame to avoid severe medication related adverse effects. Our report suggests nonatherosclerotic chronic MCA occlusion as an alternative application of tPA therapy. PMID- 29787395 TI - CORR Insights(r): What is the Success of Repeat Surgical Treatment of a Local Recurrence After Initial Wide Resection of Soft Tissue Sarcomas? PMID- 29787396 TI - Editorial: Orthopaedic Surgery, Medical Publishing, and the First Amendment of the United States Constitution. PMID- 29787397 TI - Age Differences in Health Behavior and Weight Changes in Japanese Workers: 1-Year Follow-Up Study. AB - OBJECTIVE: To examine 1-year changes in stage of health behavior change and its associations with changes in health behavior and weight in a working population cohort. METHODS: Using annual health examination data, 57,431 eligible Japanese workers aged 18 to 64 years were examined for their 1-year changes in stage of change, eating and exercise habits, and weight. RESULTS: The stages of change became polarized into the precontemplation and the action/maintenance (ie, post action) and became stabilized with increasing age. The 1-year change in stage of change was accompanied by changes in eating and exercise habits and weight. CONCLUSIONS: The age-dependent tendency towards bipolarization and stabilization of stages of change suggested that workplace health promotion interventions for facilitating health behavior changes should be started at younger ages. PMID- 29787399 TI - How Does a Changing Climate Impact the Health of Workers? Part 2: Weather and Climate Disasters, Worker Health, and Occupational Resiliency. PMID- 29787398 TI - Slips, Trips, and Falls Among Home Care Aides: A Mixed-Methods Study. AB - OBJECTIVE: To address the gap of knowledge about slips, trips, and falls (STFs) among home care aides (HCAs) who work in clients' homes. METHODS: This mixed method study used survey and focus group data of HCAs in a Medicaid-funded homecare program. RESULTS: STFs were common with over 12% of HCAs reporting occurrence in the previous 12 months, of whom 58% fell to the ground. Both survey and focus group data identified ice, clutter, workload, rushing and other hazards. Focus group data explained the reasons for not reporting STFs, even among those who sustained injury, and added HCAs' voices to the understanding of causes, consequences and prevention strategies for STFs. CONCLUSIONS: Empowering HCAs with knowledge, training, and involvement may transform "near miss" STFs into opportunities to prevent STFs among care workers and their clients. PMID- 29787400 TI - Subclinical Markers of Cardiovascular Disease Among Police Officers: A Longitudinal Assessment of the Cortisol Awakening Response and Flow Mediated Artery Dilation. AB - OBJECTIVE: To examine the association of the cortisol awakening response (CAR) with change in brachial artery flow-mediated dilation (FMD%) in police officers over a 7-year period. METHODS: Baseline CAR was obtained from four saliva samples taken 15 minutes apart immediately after awakening. Analysis of covariance was used to compare the change in FMD% (FMD%Follow-up-FMD%Baseline) across tertiles of area under the cortisol curve with respect to increase (AUCI). Regression analysis was use to assess trend. RESULTS: Officers (n = 172; 81% men) had a mean +/- SD age of 41 +/- 7.6 years. Men in the lowest AUCI tertile (ie, atypical waking cortisol pattern) had a significantly larger 7-year mean decline in FMD% (mean +/- SE: -2.56 +/- 0.64) compared with men in the highest tertile (-0.89 +/- 0.69) (P = 0.0087). CONCLUSIONS: An awakening cortisol AUCI predicted worsening of FMD% approximately 7 years later among male officers. PMID- 29787401 TI - Melatonin Receptor Agonist Ramelteon Reduces Ischemia-Reperfusion Injury Through Activation of Mitochondrial Potassium Channels. AB - Activation of melatonin receptors induces cardioprotection. Mitochondrial potassium channels (mKCa and mKATP) are involved in the signaling cascade of preconditioning. The melatonin receptor agonist ramelteon is an approved oral medication for treatment of insomnia, but nothing is known about possible cardioprotective properties. We investigated whether (1) ramelteon induces cardioprotection mediated by the melatonin receptor; (2) this effect is concentration-dependent; and (3) mKCa and/or mKATP channels are critically involved in ramelteon-induced cardioprotection. Hearts of male Wistar rats were randomized and placed on a Langendorff system, perfused with Krebs-Henseleit buffer at a constant pressure of 80 mm Hg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. Before, ischemic hearts were perfused with different concentrations of ramelteon (0.01-5 MUM) for determination of a concentration-effect curve. In subsequent experiments, the lowest protective concentration of ramelteon was administered together with paxilline (mKCa channel inhibitor) and 5-hydroxydecanoate (mKATP channel inhibitor). To determine whether the reduction of ischemia and reperfusion injury by ramelteon is mediated by melatonin receptor, we combined ramelteon with luzindole, a melatonin receptor antagonist. Infarct size was determined by triphenyltetrazolium chloride staining. In control animals, infarct size was 58% +/- 6%. Ramelteon in a concentration of 0.03 uM reduced infarct size to 28% +/- 4% (P < 0.0001 vs. Con). A lower concentration of ramelteon did not initiate cardioprotection, and higher concentrations did not further decrease infarct size. Paxilline, 5-hydroxydecanoate, and luzindole completely blocked the ramelteon-induced cardioprotection. This study shows for the first time that (1) ramelteon induces cardioprotection through melatonin receptor; (2) the effect is not concentration-dependent; and (3) activation of mKCa and mKATP channels is involved. PMID- 29787402 TI - A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery. AB - INTRODUCTION: Peripheral nerve injury is a potentially devastating complication after total shoulder arthroplasty (TSA) surgery. This pilot study aimed to assess the feasibility of using an automated somatosensory evoked potential (SSEP) device to provide a timely alert/intervention to minimize intraoperative nerve insults during TSA surgery. METHODS: A prospective, single-arm, observational study was conducted in a single university hospital. The attending anesthesiologist monitored the study participants using the EPAD automated SSEP device and an intervention was made if there was an alert during TSA surgery. The median, radial, and ulnar nerve SSEP on the operative arm, as well as the median nerve SSEP of the nonoperative arm were monitored for each patient. All patients were evaluated for postoperative neurological deficits 6 weeks postoperatively. RESULTS: In total, 21 patients were consented and were successfully monitored. In total, 4 (19%) patients developed intraoperative abnormal SSEP signal changes in the operative arm, in which 3 were reversible and 1 was irreversible till the end of surgery. Median and radial nerves were mostly involved (3/4 patients). The mean cumulative duration of nerve insult (abnormal SSEP) was 21.7+/-26.2 minutes. Univariate analysis did not identify predictor of intraoperative nerve insults. No patients demonstrated postoperative peripheral neuropathy at 6 weeks. CONCLUSIONS: A high incidence (19%) of intraoperative nerve insult was observed in this study demonstrating the feasibility of using an automated SSEP device to provide a timely alert and enable an intervention in order to minimize peripheral nerve injury during TSA. Further randomized studies are warranted. PMID- 29787404 TI - Hospital Value-Based Purchasing and Trauma-Certified Hospitals Performance. AB - INTRODUCTION: Hospital Value-Based Purchasing (HVBP) is an initiative that rewards acute-care hospitals with incentive payments for the quality of care they provide. A hospital's trauma certification has the potential to influence HVBP scores as attaining the certification provides indication of the service quality offered by the hospital. As such, this study focuses on hospitals' level of trauma certification attainment through the American College of Surgeons and whether this certification is associated with greater HVBP. METHODS: A retrospective review of the 2015 HVBP database, 2015 Area Health Resources Files (AHRF) database, and the 2015 American Hospital Association (AHA) database is utilized, and propensity score matching was employed to determine the association between level of trauma certification and scores on HVBP dimensions. RESULTS: Results reveal trauma certification is associated with lower HVBP domain scores when compared to hospitals without trauma certification. In addition, hospitals with a greater degree of trauma specialization were associated with lower total performance score and efficiency domain scores. CONCLUSIONS: Although payers attempt to connect hospital reimbursements with quality and outcomes, unintended consequences may occur. In response to these results, HVBP risk adjustment and scoring methods should receive further scrutiny. PMID- 29787403 TI - Driving Comparisons Between Young Adults with Autism Spectrum Disorder and Typical Development. AB - OBJECTIVE: Many individuals with autism spectrum disorder (ASD) are reluctant to pursue driving because of concerns about their ability to drive safely. This study aimed to assess differences in simulated driving performance in young adults with ASD and typical development, examining relationships between driving performance and the level of experience (none, driver's permit, licensed) across increasingly difficult driving environments. METHOD: Participants included 50 English-speaking young adults (16-26 years old) with ASD matched for sex, age, and licensure with 50 typically-developing (TD) peers. Participants completed a structured driving assessment using a virtual-reality simulator that included increasingly complex environmental demands. Differences in mean speed and speed and lane variability by diagnostic group and driving experience were analyzed using multilevel linear modeling. RESULTS: Young adults with ASD demonstrated increased variability in speed and lane positioning compared with controls, even during low demand tasks. When driving demands became more complex, group differences were moderated by driving experience such that licensed drivers with ASD drove similarly to TD licensed drivers for most tasks, whereas unlicensed drivers with ASD had more difficulty with speed and lane management than TD drivers. CONCLUSION: Findings suggest that young adults with ASD may have more difficulty with basic driving skills than peers, particularly in the early stages of driver training. Increased difficulty compared with peers increases as driving demands become more complex, suggesting that individuals with ASD may benefit from a slow and gradual approach to driver training. Future studies should evaluate predictors of driving performance, on-road driving, and ASD-specific driving interventions. PMID- 29787405 TI - Introducing a Clinical Documentation Specialist to Improve Coding and Collectability on a Surgical Service. AB - INTRODUCTION: Inadequate electronic medical record (EMR) documentation remains a significant source of revenue loss. The Department of Surgery in a trauma and tertiary care teaching hospital developed a revenue optimization initiative for inpatients on general, vascular, and trauma surgery and surgical intensive care unit services to enhance clinical documentation and increase revenue capture. METHODS: Clinical documentation management program included six trained clinical documentation specialists (CDSs), five physician assistants (PAs), directors of health information management (HIM), and two surgical champions. Lean methodology was applied to develop a coding and documentation program wherein trained CDS polled ICD-10 codes in the surgical EMR for accuracy in diagnoses documentation. An opportunity for improved documentation prompted query generation for a specially trained PA review. Physician assistant adjusted EMR documentation according to query to more accurately describe high impact diagnoses. Outcomes included PA query response rate, potential revenue opportunities, validated revenue gains, and missed revenue opportunity. RESULTS: Twelve thousand EMRs were queried in the study interval. $2,206,620.16 in validated revenues were realized. Interestingly, we identified $1,792,591.91 in potential opportunities and $65,097.30 in lost opportunities. Query response rate increased from 17% to 94.7%. CONCLUSIONS: The authors demonstrate a concentrated Coding and Documentation Program involving CDS, and Surgical PAs results in significant revenue gains for an inpatient surgery service in a public hospital. PMID- 29787406 TI - Effect of Patient and Provider Education on Antibiotic Overuse for Respiratory Tract Infections. AB - Antibiotic overuse for respiratory tract infections (RTIs) in primary care (PC) is a known important contributor to the serious health threat of antibiotic resistance, yet remains a difficult problem to improve. The purpose of the study was to assess the effects of a combination patient and provider education program on antibiotic prescribing in RTIs in a rural primary care clinic. Utilizing a quasi-experimental pretest-posttest design, a retrospective electronic medical record review was conducted to determine if a patient and provider education program changed the rates of antibiotics being prescribed (immediate or delayed) during a visit for RTI for 207 randomly selected patients during the established evaluation time periods. The antibiotic prescription rate for the preintervention group was 56.3% compared to 28.8% for the postintervention group (p < .01). Immediate antibiotics were ordered in the preintervention group 31.1% of the time compared to 13.5% for the postintervention group (p < .05). The results of this study demonstrate that educational interventions can be effective in rural settings and that changes in antibiotic prescribing are possible. PMID- 29787407 TI - Identifying Barriers to Implementation of the National Partnership for Maternal Safety Obstetric Hemorrhage Bundle at a Tertiary Center: Utilization of the Delphi Method. AB - BACKGROUND: In 2015, the National Partnership for Maternal Safety (NPMS) developed an obstetric hemorrhage consensus bundle to provide birthing facilities in the United States with consistent, validated practice guidelines for postpartum hemorrhage management. The process of implementing each bundle element at a large tertiary labor and delivery unit has not been described; we sought to identify practice deficiencies and perceived barriers to bundle implementation among multidisciplinary providers. METHODS: We conducted a prospective, cross sectional, consensus-building study based on the Delphi method. A multidisciplinary expert panel comprised of anesthesiologists, obstetricians, nurses, and surgical technicians was assembled and participated in 4 sequential questionnaires. The first round identified bundle elements that experts determined as not currently adequate and perceived barriers to implementation. The second round established prioritization of elements within each professional group; and the third round ranked the elements with at least 60% agreement on feasibility of implementation and positive impact on patient care. The last round revealed responses across all 4 professional groups to derive a final consensus. Descriptive statistics were performed. RESULTS: A total of 38 experts completed the study (11 anesthesiologists, 11 obstetricians, 10 nurses, and 6 surgical technicians). While all 13 (100%) NPMS obstetric bundle elements were described as deficient in our labor and delivery unit by a provider in at least 1 discipline, consensus among at least 3 of the 4 disciplines was achieved for 6 element deficiencies. Barriers to implementation were determined. The initiatives that achieved consensus as possessing high patient impact and implementation feasibility were protocol-driven management, unit-based simulation drills, blood loss quantification, and team huddles and debriefings. CONCLUSIONS: The NPMS obstetric hemorrhage bundle was created to help guide practice and systems improvement for US birthing facilities. The Delphi method enabled identification of deficient elements and perceived barriers to element implementation, as well as group consensus on elements with highest patient impact and feasibility. Multidisciplinary group consensus can identify deficiencies and promote tangible, quality improvements in a large, tertiary-care labor and delivery unit. Institutions may utilize our described technique to guide implementation of future care bundles. PMID- 29787408 TI - Organ Donation After Circulatory Death: Ethical Issues and International Practices. AB - Donation after circulatory death (DCD) is an increasingly utilized practice that can contribute to reducing the difference between the supply of organs and the demand for organs for transplantation. As the number of transplanted organs from DCD donors continues to increase, there is an essential need to address the ethical aspects of DCD in institutional DCD protocols and clinical practice. Ethical issues of respecting the end-of-life wishes of a potential donor, respecting a recipient's wishes, and addressing potential conflicts of interest are important considerations in developing policies and procedures for DCD programs. Although there may be diversity among DCD programs in Europe, Australia, Israel, China, the United States, and Canada, addressing ethical considerations in these DCD programs is essential to respect donors and recipients during the altruistic and generous act of organ donation. PMID- 29787409 TI - "Modified Dynamic Needle Tip Positioning" Short-Axis, Out-of-Plane, Ultrasound Guided Radial Artery Cannulation in Neonates: A Randomized Controlled Trial. AB - BACKGROUND: Radial artery cannulation is extremely challenging in neonatal patients. Herein, we compared the success rate of the modified dynamic needle tip positioning short-axis, out-of-plane, ultrasound-guided technique with that of the traditional palpation technique in neonatal radial artery cannulation. METHODS: Sixty term neonates undergoing major abdominal surgery were randomized into the ultrasound or palpation group via the sealed-envelope method. The ultrasound group underwent radial artery cannulation using an ultrasonic apparatus, while traditional palpation of arterial pulsation was used in the palpation group. The arterial diameter and depth were measured on ultrasound before the puncture. We recorded age, weight, sex, and other background characteristics. The primary outcomes included the first-attempt, total success rates, and the total puncture procedure duration. Secondary outcomes included the incidence of complications (hematoma and thrombosis). Data were compared between the 2 groups. RESULTS: Sixty term neonates were enrolled in the study. The success rates of the first attempt in the ultrasound and palpation groups were 40% (n = 30) and 10% (n = 30), respectively (P = .007; relative risk, 4.0; 95% confidence interval, 1.3-12.8). The total success rate was 96.7% in the ultrasound group and 60.0% in the palpation group (P = .001; relative risk, 1.61; 95% confidence interval, 1.19-2.17). The average time to accomplish radial artery cannulation in the ultrasound and palpation groups was 91.4 +/- 55.4 and 284.7 +/ 153.6 seconds, respectively (P < .001; estimated difference, -193; 95% confidence interval, -256 to -130). In addition, 3.3% of the patients in the ultrasound group and 26.7% in the palpation group suffered puncture hematoma (P = .026; relative risk, 0.13; 95% confidence interval, 0.02-0.94). CONCLUSIONS: Modified dynamic needle tip positioning short-axis, out-of-plane, ultrasound guided radial artery cannulation in neonates improves the first-attempt and total success rates and decreases the total procedural time and incidence of cannulation-related complications. PMID- 29787410 TI - The Effect of Dexmedetomidine on Propofol Requirements During Anesthesia Administered by Bispectral Index-Guided Closed-Loop Anesthesia Delivery System: A Randomized Controlled Study. AB - BACKGROUND: Dexmedetomidine, a selective alpha2-adrenergic agonist currently approved for continuous intensive care unit sedation, is being widely evaluated for its role as a potential anesthetic. The closed-loop anesthesia delivery system (CLADS) is a method to automatically administer propofol total intravenous anesthesia using bi-spectral index (BIS) feedback and attain general anesthesia (GA) steady state with greater consistency. This study assessed whether dexmedetomidine is effective in further lowering the propofol requirements for total intravenous anesthesia facilitated by CLADS. METHODS: After ethics committee approval and written informed consent, 80 patients undergoing elective major laparoscopic/robotic surgery were randomly allocated to receive GA with propofol CLADS with or without the addition of dexmedetomidine. Quantitative reduction of propofol and quality of depth-of-anesthesia (primary objectives), intraoperative hemodynamics, incidence of postoperative adverse events (sedation, analgesia, nausea, and vomiting), and intraoperative awareness recall (secondary objectives) were analyzed. RESULTS: There was a statistically significant lowering of propofol requirement (by 15%) in the dexmedetomidine group for induction of anesthesia (dexmedetomidine group: mean +/- standard deviation 0.91 +/- 0.26 mg/kg; nondexmedetomidine group: 1.07 +/- 0.23 mg/kg, mean difference: 0.163, 95% CI, 0.04-0.28; P = .01) and maintenance of GA (dexmedetomidine group: 3.25 +/- 0.97 mg/kg/h; nondexmedetomidine group: 4.57 +/- 1.21 mg/kg/h, mean difference: 1.32, 95% CI, 0.78-1.85; P < .001). The median performance error of BIS control, a measure of bias, was significantly lower in dexmedetomidine group (1% [-5.8%, 8%]) versus nondexmedetomidine group (8% [2%, 12%]; P = .002). No difference was found for anesthesia depth consistency parameters, including percentage of time BIS within +/-10 of target (dexmedetomidine group: 79.5 [72.5, 85.3]; nondexmedetomidine group: 81 [68, 88]; P = .534), median absolute performance error (dexmedetomidine group: 12% [10%, 14%]; nondexmedetomidine group: 12% [10%, 14%]; P = .777), wobble (dexmedetomidine group: 10% [8%, 10%]; nondexmedetomidine group: 8% [6%, 10%]; P = .080), and global score (dexmedetomidine group: 25.2 [23.1, 35.8]; nondexmedetomidine group: 24.7 [20, 38.1]; P = .387). Similarly, there was no difference between the groups for percentage of time intraoperative heart rate and mean arterial pressure remained within 20% of baseline. However, addition of dexmedetomidine to CLADS propofol increased the incidence of significant bradycardia (dexmedetomidine group: 14 [41.1%]; nondexmedetomidine group: 3 [9.1%]; P = .004), hypotension (dexmedetomidine group: 9 [26.5%]; nondexmedetomidine group: 2 [6.1%]; P = .045), and early postoperative sedation. CONCLUSIONS: The addition of dexmedetomidine to propofol administered by CLADS was associated with a consistent depth of anesthesia along with a significant decrease in propofol requirements, albeit with an incidence of hemodynamic depression and early postoperative sedation. PMID- 29787411 TI - Perianesthetic and Anesthesia-Related Mortality in a Southeastern United States Population: A Longitudinal Review of a Prospectively Collected Quality Assurance Data Base. AB - BACKGROUND: Perianesthetic mortality (death occurring within 48 hours of an anesthetic) continues to vary widely depending on the study population examined. The authors study in a private practice physician group that covers multiple anesthetizing locations in the Southeastern United States. This group has in place a robust quality assurance (QA) database to follow all patients undergoing anesthesia. With this study, we estimate the incidence of anesthesia-related and perianesthetic mortality in this QA database. METHODS: Following institutional review board approval, data from 2011 to 2016 were obtained from the QA database of a large, community-based anesthesiology group practice. The physician practice covers 233 anesthetizing locations across 20 facilities in 2 US states. All detected cases of perianesthetic death were extracted from the database and compared to the patients' electronic medical record. These cases were further examined by a committee of 3 anesthesiologists to determine whether the death was anesthesia related (a perioperative death solely attributable to either the anesthesia provider or anesthetic technique), anesthetic contributory (a perioperative death in which anesthesia role could not be entirely excluded), or not due to anesthesia. RESULTS: A total of 785,467 anesthesia procedures were examined from the study period. A total of 592 cases of perianesthetic deaths were detected, giving an overall death rate of 75.37 in 100,000 cases (95% CI, 69.5-81.7). Mortality judged to be anesthesia related was found in 4 cases, giving a mortality rate of 0.509 in 100,000 (95% CI, 0.198-1.31). Mortality judged to be anesthesia contributory were found in 18 cases, giving a mortality of 2.29 in 100,000 patients (95% CI, 1.45-3.7). A total of 570 cases were judged to be nonanesthesia related, giving an incidence of 72.6 per 100,000 anesthetics (95% CI, 69.3-75.7). CONCLUSIONS: In a large, comprehensive database representing the full range of anesthesia practices and locations in the Southeastern United States, the rate of perianesthestic death was 0.509 in 100,000 (95% CI, 0.198 1.31). Future in-depth analysis of the epidemiology of perianesthetic deaths will be reported in later studies. PMID- 29787412 TI - Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness in Mechanically Ventilated Patients? A Systematic Review and Meta analysis. AB - BACKGROUND: We performed a systematic review and meta-analysis of studies investigating the diagnostic accuracy of respiratory variation in inferior vena cava diameter (DeltaIVC) for predicting fluid responsiveness in patients receiving mechanical ventilation. METHODS: MEDLINE, EMBASE, the Cochrane Library, and Web of Science were screened from inception to February 2017. The meta analysis assessed the pooled sensitivity, specificity, diagnostic odds ratio, and area under the receiver operating characteristic curve. In addition, heterogeneity and subgroup analyses were performed. RESULTS: A total of 12 studies involving 753 patients were included. Significant heterogeneity existed among the studies, and meta-regression indicated that ventilator settings were the main sources of heterogeneity. Subgroup analysis indicated that DeltaIVC exhibited better diagnostic performance in the group of patients ventilated with tidal volume (TV) >=8 mL/kg and positive end-expiratory pressure (PEEP) <=5 cm H2O than in the group ventilated with TV <8 mL/kg or PEEP >5 cm H2O, as demonstrated by higher sensitivity (0.80 vs 0.66; P = .02), specificity (0.94 vs 0.68; P < .001), diagnostic odds ratio (68 vs 4; P < .001), and area under the receiver operating characteristic curve (0.88 vs 0.70; P < .001). The best DeltaIVC threshold for predicting fluid responsiveness was 16% +/- 2% in the group of TV >=8 mL/kg and PEEP <=5 cm H2O, whereas in the group of TV <8 mL/kg or PEEP >5 cm H2O, this threshold was 14% +/- 5%. CONCLUSIONS: DeltaIVC shows limited ability for predicting fluid responsiveness in distinct ventilator settings. In patients with TV >=8 mL/kg and PEEP <=5 cm H2O, DeltaIVC was an accurate predictor of fluid responsiveness, while in patients with TV <8 mL/kg or PEEP >5 cm H2O, DeltaIVC was a poor predictor. Thus, intensivists must be cautious when using DeltaIVC. PMID- 29787413 TI - Halving the Volume of AnaConDa: Evaluation of a New Small-Volume Anesthetic Reflector in a Test Lung Model. AB - BACKGROUND: Volatile anesthetics are increasingly used for sedation in intensive care units. The most common administration system is AnaConDa-100 mL (ACD-100; Sedana Medical, Uppsala, Sweden), which reflects volatile anesthetics in open ventilation circuits. AnaConDa-50 mL (ACD-50) is a new device with half the volumetric dead space. Carbon dioxide (CO2) can be retained with both devices. We therefore compared the CO2 elimination and isoflurane reflection efficiency of both devices. METHODS: A test lung constantly insufflated with CO2 was ventilated with a tidal volume of 500 mL at 10 breaths/min. End-tidal CO2 (EtCO2) partial pressure was measured using 3 different devices: a heat-and-moisture exchanger (HME, 35 mL), ACD-100, and ACD-50 under 4 different experimental conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS) conditions, BTPS with 0.4 Vol% isoflurane (ISO-0.4), and BTPS with 1.2 Vol% isoflurane. Fifty breaths were recorded at 3 time points (n = 150) for each device and each condition. To determine device dead space, we adjusted the tidal volume to maintain normocapnia (n = 3), for each device. Thereafter, we determined reflection efficiency by measuring isoflurane concentrations at infusion rates varying from 0.5 to 20 mL/h (n = 3), for each device. RESULTS: EtCO2 was consistently greater with ACD-100 than with ACD-50 and HME (ISO-0.4, mean +/- standard deviations: ACD-100, 52.4 +/- 0.8; ACD-50, 44.4 +/- 0.8; HME, 40.1 +/- 0.4 mm Hg; differences of means of EtCO2 [respective 95% confidence intervals]: ACD-100 - ACD-50, 8.0 [7.9-8.1] mm Hg, P < .001; ACD-100 - HME, 12.3 [12.2-12.4] mm Hg, P < .001; ACD-50 - HME, 4.3 [4.2-4.3] mm Hg, P < .001). It was greatest under ATP, less under BTPS, and least with ISO-0.4 and BTPS with 1.2 Vol% isoflurane. In addition to the 100 or 50 mL "volumetric dead space" of each AnaConDa, "reflective dead space" was 40 mL with ACD-100 and 25 mL with ACD-50 when using isoflurane. Isoflurane reflection was highest under ATP. Under BTPS with CO2 insufflation and isoflurane concentrations around 0.4 Vol%, reflection efficiency was 93% with ACD-100 and 80% with ACD-50. CONCLUSIONS: Isoflurane reflection remained sufficient with the ACD-50 at clinical anesthetic concentrations, while CO2 elimination was improved. The ACD-50 should be practical for tidal volumes as low as 200 mL, allowing lung-protective ventilation even in small patients. PMID- 29787414 TI - Perioperative Peripheral Nerve Injury After General Anesthesia: A Qualitative Systematic Review. AB - Perioperative peripheral nerve injury (PNI) is a well-recognized complication of general anesthesia that continues to result in patient disability and malpractice claims. However, the multifactorial etiology of PNI is often not appreciated in malpractice claims given that most PNI is alleged to be due to errors in patient positioning. New advances in monitoring may aid anesthesiologists in the early detection of PNI. This article reviews recent studies of perioperative PNI after general anesthesia and discusses the epidemiology and potential mechanisms of injury and preventive measures. We performed a systematic literature search, reviewed the available evidence, and identified areas for further investigation. We also reviewed perioperative PNI in the Anesthesia Closed Claims Project database for adverse events from 1990 to 2013. The incidence of perioperative PNI after general anesthesia varies considerably depending on the type of surgical procedure, the age and risk factors of the patient population, and whether the detection was made retrospectively or prospectively. Taken together, studies suggest that the incidence in a general population of surgical patients undergoing all types of procedures is <1%, with higher incidence in cardiac, neurosurgery, and some orthopedic procedures. PNI represent 12% of general anesthesia malpractice claims since 1990, with injuries to the brachial plexus and ulnar nerves representing two-thirds of PNI claims. The causes of perioperative PNI after general anesthesia are likely multifactorial, resulting in a "difficult to predict and prevent" phenomenon. Nearly half of the PNI closed claims did not have an obvious etiology, and most (91%) were associated with appropriate anesthetic care. Future studies should focus on the interaction between different mechanisms of insult, severity and duration of injury, and underlying neuronal reserves. Recent automated detection technology in neuromonitoring with somatosensory evoked potentials may increase the ability to identify at-risk patients and individualize patient management. PMID- 29787416 TI - Cecal Ligation and Puncture Alters Glucocorticoid Receptor Expression. AB - OBJECTIVES: Interventional trials on glucocorticoids in sepsis have yielded capricious results. Recent studies have identified multiple glucocorticoid receptor isoforms. The relative abundance of these isoforms in septic patients and following murine cecal ligation and puncture is unknown. The objective of this study is to determine the effects of cecal ligation and puncture on glucocorticoid receptor isoform abundance. DESIGN: Determination of effects of cecal ligation and puncture on glucocorticoid receptor isoform subtype abundance in C57BL/6 mice. Examination of glucocorticoid receptor isoform abundance in tissues harvested from patients immediately after death from sepsis or nonseptic critical illness. SETTING: Research laboratory. SUBJECTS: C57BL/6 mice and human tissue sections from recently deceased critically ill patients. INTERVENTIONS: C57BL/6 mice were subjected to cecal ligation and puncture or sham operation. Abundance of the activating glucocorticoid receptor alpha and the inactivating glucocorticoid receptor beta isoforms was determined in mouse and human tissue using immunoblotting. Cardiac output with or without stimulation with dexamethasone was assessed using echocardiography. The expression of the gene encoding the glucocorticoid-dependent enzyme glucose-6-phosphatase was identified using polymerase chain reaction. Statistical significance (p < 0.05) was determined using analysis of variance. MEASUREMENTS AND MAIN RESULTS: Results in baseline and sham operation mice were identical. At baseline, glucocorticoid receptor alphaA predominated in heart, lung, and skeletal muscle; abundance was decreased post cecal ligation and puncture. All glucocorticoid receptor alpha subtypes were identified in liver. Cecal ligation and puncture decreased the summed abundance of hepatic glucocorticoid receptor alpha subtypes and those of glucocorticoid receptors alphaA, B, and D. However, glucocorticoid receptor alphaC abundance was unchanged. Cecal ligation and puncture increased glucocorticoid receptor beta protein abundance in the heart and lung. Relative to T0, cecal ligation and puncture decreased cardiac output and attenuated the cardiac output response to dexamethasone. Cecal ligation and puncture also decreased expression of glucose-6-phosphatase. Compared with nonseptic patients, human sepsis decreased the abundance of glucocorticoid receptor alpha and increased the abundance of glucocorticoid receptor beta in heart and liver biopsies. CONCLUSIONS: Cecal ligation and puncture altered glucocorticoid receptor alpha and glucocorticoid receptor beta isoform expression in tissues and decreased functional responses in heart and liver. Decreases in glucocorticoid receptor alpha and increases in glucocorticoid receptor beta might explain the diminished glucocorticoid responsiveness observed in sepsis. PMID- 29787417 TI - Human leukocyte antigen mismatch and precision medicine in transplantation. AB - PURPOSE OF REVIEW: Pretransplant and posttransplant alloimmune risk assessment needs to evolve towards a precision medicine model already used in other areas of medicine. Although this has not been possible with traditional risk factors available at the time of transplant, new methods of human leukocyte antigen (HLA) molecular mismatch have generated hope that alloimmune risk assessment may be precise enough for personalized treatment strategies. RECENT FINDINGS: This review describes the various HLA molecular mismatch methods and some of the recent publications for each method. These include studies that have evaluated HLA molecular mismatch in the context of lung, pancreas and kidney transplant as a correlate with short and long-term outcomes. The limitations of traditional alloimmune risk assessment strategies are highlighted in the context of individualized patient care. CONCLUSION: Recent studies that have evaluated HLA molecular mismatch in the context of immunosuppression minimization are examples of how more precise measurements of alloimmune risk can lead to novel insights that may help personalize immunosuppression protocols. PMID- 29787415 TI - Co-Occurrence of Post-Intensive Care Syndrome Problems Among 406 Survivors of Critical Illness. AB - OBJECTIVES: To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post intensive care syndrome problems. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs from five U.S. centers. PATIENTS: Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an Acute Physiology and Chronic Health Evaluation II of 23. At 3 and 12 months, one or more post-intensive care syndrome problems were present in 64% and 56%, respectively. Nevertheless, co-occurring post-intensive care syndrome problems (i.e., in two or more domains) were present in 25% at 3 months and 21% at 12 months. Post-intensive care syndrome problems in all three domains were present in only 6% at 3 months and 4% at 12 months. More years of education was associated with greater odds of being post-intensive care syndrome free (p < 0.001 at 3 and 12 mo). More severe frailty was associated with lower odds of being post-intensive care syndrome free (p = 0.005 at 3 mo and p = 0.048 at 12 mo). CONCLUSIONS: In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors. PMID- 29787418 TI - Nonalcoholic fatty liver disease and albuminuria: a systematic review and meta analysis. AB - BACKGROUND/OBJECTIVES: The relationship between nonalcoholic fatty liver disease (NAFLD) and albuminuria has been shown in many epidemiologic studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data and to estimate the risk of albuminuria among patients with NAFLD. METHODS: Comprehensive literature review was conducted utilizing Medline and Embase database through January 2018 to identify studies that compared the risk of albuminuria among patients with NAFLD versus those without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Nineteen studies (17 cross-sectional studies and two cohort studies) with 24 804 participants fulfilled the eligibility criteria and were included in this meta analysis. The risk of albuminuria among patients with NAFLD was significantly higher than those without NAFLD with the pooled odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.32-2.11]. Subgroup analysis demonstrated the significantly increased risk of albuminuria among patients with NAFLD without diabetes with pooled OR of 2.25 (95% CI: 1.65-3.06). However, we found no significant association between albuminuria and NAFLD among diabetic patients [pooled OR 1.28 (95% CI: 0.94-1.75)]. CONCLUSION: A significantly increased risk of albuminuria among patients with NAFLD was observed in this meta-analysis. Physicians should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria especially in patients with NAFLD. PMID- 29787420 TI - Letter to the Editor. PMID- 29787421 TI - The Impact of Saphenous Vein Sparing During Inguinal Lymphadenectomy on Postoperative Morbidity in Women With Vulval Cancer: An Updated Per-Groin Meta analysis of Short-term Outcomes. AB - OBJECTIVE: Inguinofemoral lymphadenectomy (IFL) is included in the standard surgical management of early-stage vulval cancer (VC) but is often accompanied by surgical complications. Efforts have been made to limit the postoperative morbidity by adopting more conservative IFL techniques without compromising the surgical outcomes. Saphenous vein (SV) preservation during IFL for VC appears to reduce the incidence of postoperative complications including lymphedema. To ascertain the efficacy of SV preservation, we aimed to revisit the impact of SV preservation on short-term per groin complications by updating on a previous meta analysis to further guide current clinical practice. METHODS: A systematic literature review was conducted to identify studies that reported postoperative complications following IFL with SV preservation and controls (SV ligation during IFL) in VC patients. We included articles in English language and avoided date restrictions. Direct-comparison meta-analysis was performed between the use of SV preservation and SV ligation for the short-term outcomes of lymphedema, cellulitis, and wound dehiscence/breakdown. Fixed- and random-effects models were fitted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Five studies were included in the final analysis. Direct-comparison per groin meta-analysis between SV preservation and SV ligation significantly decreased the odds for developing lymphedema (OR, 0.363; 95% CI, 0.228-0.578; P < 0.001), cellulitis (OR, 0.481; 95% CI, 0.28-0.825; P = 0.008), and wound dehiscence/breakdown (OR, 0.296; 95% CI, 0.191-0.458; P < 0.001). When SV sparing was clearly the sole intervention, lymphedema was the only complication in which the positive effect of SV sparing is exerted (OR, 0.28; 95% CI, 0.149-0.526; P < 0.001). CONCLUSIONS: This per groin meta-analysis updates on the current evidence suggesting the SV sparing improves postoperative outcomes following IFL in VC patients. Where sentinel biopsy is not indicated, this risk-reducing strategy should be considered in selected VC patients undergoing IFL until a multicenter randomized controlled trial becomes available. PMID- 29787422 TI - Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. AB - OBJECTIVES: Recent data support the use of pembrolizumab in cervical cancer. The aim of this study was to investigate pembrolizumab in heavily pretreated patients with recurrent cervical cancer. METHODS: Data from consecutive patients treated with pembrolizumab at a single academic institution were assessed. Programmed cell death ligand 1 (PD-L1) status and microsatellite instability were assessed from tumor samples. Irrespective of PD-L1 expression status, pembrolizumab was administered at fixed dose of 200 mg intravenously every 3 weeks. Treatment response was evaluated by computed tomography, using iRECIST (2017) criteria. Descriptive statistics were performed. Results from previous publications were summarized. RESULTS: In total, 11 heavily pretreated patients with recurrent cervical cancer received pembrolizumab. Of these, 2 (18%) patients showed partial response and 2 (18%) patients showed disease stabilization on computed tomography, resulting in a clinical benefit rate of 36%. These 4 patients are still on treatment and durable antitumor activity of up to 52 weeks was observed. Treatment was generally well tolerated with 1 patient showing dose-limiting toxicity. Median overall survival was 26 (3-53) weeks, and a 6-month overall survival rate of 65% was observed. Of the 5 patients with high PD-L1 expression, 3 showed response to treatment. CONCLUSIONS: Pembrolizumab shows promising activity in heavily pretreated patients with recurrent cervical cancer in a real life clinical setting. Treatment was generally well tolerated, and adverse effects were manageable. Growing evidence supports the use of pembrolizumab in this group of patients. PMID- 29787419 TI - A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease. AB - BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. PATIENTS AND METHODS: We performed the first genome wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5*10) were replicated in 56 independent French and Dutch patients with RCDII. RESULTS: After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37*10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. CONCLUSION: We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression. PMID- 29787423 TI - Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy. AB - Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy. PMID- 29787424 TI - Conrad-Global Conference on Radiation Topics: Preparedness, Response, Protection, and Research, Munich, 8-11 May 2017. PMID- 29787426 TI - Actinide-contaminated Skin: Comparing Decontamination Efficacy of Water, Cleansing Gels, and DTPA Gels. AB - Skin contamination by alpha-emitting actinides is a risk to workers during nuclear fuel production and reactor decommissioning. Also, the list of items for potential use in radiological dispersal devices includes plutonium and americium. The actinide chemical form is important and solvents such as tributyl phosphate, used to extract plutonium, can influence plutonium behavior. This study investigated skin fixation and efficacy of decontamination products for these actinide forms using viable pig skin in the Franz cell diffusion system. Commonly used or recommended decontamination products such as water, cleansing gel, diethylenetriamine pentaacetic acid, or octadentate hydroxypyridinone compound 3,4,3-LI(1,2-HOPO), as well as diethylenetriamine pentaacetic acid hydrogel formulations, were tested after a 2-h contact time with the contaminant. Analysis of skin samples demonstrated that more plutonium nitrate is bound to skin as compared to plutonium-tributyl phosphate, and fixation of americium to skin was also significant. The data show that for plutonium-tributyl phosphate all the products are effective ranging from 80 to 90% removal of this contaminant. This may be associated with damage to the skin by this complex and suggests a mechanical/wash-out action rather than chelation. For removal of americium and plutonium, both Trait Rouge cleansing gel and diethylenetriamine pentaacetic acid are better than water, and diethylenetriamine pentaacetic acid hydrogel is better than Osmogel. The different treatments, however, did not significantly affect the activity in deeper skin layers, which suggests a need for further improvement of decontamination procedures. The new diethylenetriamine pentaacetic acid hydrogel preparation was effective in removing americium, plutonium, and plutonium tributyl phosphate from skin; such a formulation offers advantages and thus merits further assessment. PMID- 29787425 TI - A Metabolomic Serum Signature from Nonhuman Primates Treated with a Radiation Countermeasure, Gamma-tocotrienol, and Exposed to Ionizing Radiation. AB - The search for and development of radiation countermeasures to treat acute lethal radiation injury has been underway for the past six decades, resulting in the identification of multiple classes of radiation countermeasures. However, to date only granulocyte colony-stimulating factor (Neupogen) and PEGylated granulocyte colony-stimulating factor (Neulasta) have been approved by the U.S. Food and Drug Administration for the treatment of hematopoietic acute radiation syndrome. Gamma tocotrienol has demonstrated radioprotective efficacy in murine and nonhuman primate models. Currently, this agent is under advanced development as a radioprotector, and the authors are trying to identify its efficacy biomarkers. In this study, global metabolomic changes were analyzed using ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry. The pilot study using 16 nonhuman primates (8 nonhuman primates each in gamma-tocotrienol- and vehicle-treated groups), with samples obtained from gamma-tocotrienol-treated and irradiated nonhuman primates, demonstrates several metabolites that are altered after irradiation, including compounds involved in fatty acid beta oxidation, purine catabolism, and amino acid metabolism. The machine-learning algorithm, Random Forest, separated control, irradiated gamma-tocotrienol treated, and irradiated vehicle-treated nonhuman primates at 12 h and 24 h as evident in a multidimensional scaling plot. Primary metabolites validated included carnitine/acylcarnitines, amino acids, creatine, and xanthine. Overall, gamma-tocotrienol administration reduced high fluctuations in serum metabolite levels, suggesting an overall beneficial effect on animals exposed to radiation. This initial assessment also highlights the utility of metabolomics in determining underlying physiological mechanisms responsible for the radioprotective efficacy of gamma-tocotrienol. PMID- 29787427 TI - Impact of Ionizing Radiation on Electrophysiological Behavior of Human-induced Ipsc-derived Cardiomyocytes on Multielectrode Arrays. AB - Cardiac arrhythmia presumably induced through cardiac fibrosis is a recurrent long-term consequence of exposure to ionizing radiation. However, there is also evidence that cardiac arrhythmia can occur in patients shortly after irradiation. In this study, the authors employed multielectrode arrays to investigate the short-term effects of x-ray radiation on the electrophysiological behavior of cardiomyocytes derived from human-induced pluripotent stem cells. These cardiomyocytes with spontaneous pacemaker activity were cultured on single-well multielectrode arrays. After exposure to 0, 0.5, 1, 2, 5, 10 Gy x-ray radiation, electrical activity was measured at time points ranging from 10 min to 96 h. RNA sequencing was employed to verify the expression of genes specifically involved in cardiomyocyte differentiation and function. A decrease in beating rate was observed after irradiation with 5 and 10 Gy starting 48 h after exposure. Cells exposed to higher doses of radiation were more prone to show changes in electrophysiological spatial distribution. No radiation-induced effects with respect to the corrected QT interval were detectable. Gene expression analysis showed up regulation of typical cardiac features like ACTC1 or HCN4. In this study, early dose-dependent changes in electrophysiological behavior were determined after x-ray irradiation. Results point towards a dose-dependent effect on pacemaker function of cardiomyocytes and indicate a possible connection between irradiation and short-term changes in electrophysiological cardiac function. Cardiomyocytes derived from human-induced pluripotent stem cells on multielectrode arrays represent a promising in vitro cardiac-modeling system for preclinical studies. PMID- 29787428 TI - Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models. AB - Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications. A panel of protein biomarkers was measured on plasma samples collected at 0 to 28 d after exposure using electrochemiluminescence-detection technology. The database was split into two distinct groups (i.e., "calibration," n = 11; "validation," n = 7). The calibration database was used in an initial stepwise regression multivariate model-fitting approach followed by down selection of biomarkers for identification of subpanels of hematopoietic acute radiation syndrome-responsive biomarkers for three time windows (i.e., 0-2 d, 2-7 d, 7-28 d). Model 1 (0-2 d) includes log C-reactive protein (p < 0.0001), log interleukin-13 (p < 0.0054), and procalcitonin (p < 0.0316) biomarkers; model 2 (2-7 d) includes log CD27 (p < 0.0001), log FMS-related tyrosine kinase 3 ligand (p < 0.0001), log serum amyloid A (p < 0.0007), and log interleukin-6 (p < 0.0002); and model 3 (7-28 d) includes log CD27 (p < 0.0012), log serum amyloid A (p < 0.0002), log erythropoietin (p < 0.0001), and log CD177 (p < 0.0001). The predicted risk of radiation injury categorization values, representing the hematopoietic acute radiation syndrome severity outcome for the three models, produced least squares multiple regression fit confidences of R = 0.73, 0.82, and 0.75, respectively. The resultant algorithms support the proof of concept that plasma proteomic biomarkers can supplement clinical signs and symptoms to assess hematopoietic acute radiation syndrome risk severity. PMID- 29787430 TI - Successful Teaching of Radiobiology Students in the Medical Management of Acute Radiation Effects From Real Case Histories Using Clinical Signs and Symptoms and Taking Advantage of Recently Developed Software Tools. AB - In 2015, the Bundeswehr Institute of Radiobiology organized a North Atlantic Treaty Organization exercise to examine the significance of clinical signs and symptoms for the prediction of late-occurring acute radiation syndrome. Cases were generated using either the Medical Treatment Protocols for Radiation Accident Victims (METREPOL, n = 167) system or using real-case descriptions extracted from a database system for evaluation and archiving of radiation accidents based on case histories (SEARCH, n = 24). The cases ranged from unexposed [response category 0 (RC 0, n = 89)] to mild (RC 1, n = 45), moderate (RC 2, n = 19), severe (RC 3, n = 20), and lethal (RC 4, n = 18) acute radiation syndrome. During the previous exercise, expert teams successfully predicted hematological acute radiation syndrome severity, determined whether hospitalization was required, and gave treatment recommendations, taking advantage of different software tools developed by the North Atlantic Treaty Organization teams. The authors provided the same data set to radiobiology students who were introduced to the medical management of acute effects after radiation exposure and the software tools during a class lasting 15 h. Corresponding to the previous results, difficulties in the discrimination between RC 0/RC 1 and RC 3/RC 4, as well as a systematic underestimation of RC 1 and RC 2, were observed. Nevertheless, after merging reported response categories into clinically relevant groups (RC 0-1, RC 2-3, and RC 3-4), it was found that the majority of cases (95.2% +/- 2.2 standard deviations) were correctly identified and that 94.7% (+/-2.6 standard deviations) developing acute radiation syndrome and z96.4% (+/-1.6 standard deviations) requiring hospitalization were identified correctly. Two out of three student teams also provided a dose estimate. These results are comparable to the best-performing team of the 2015 North Atlantic Treaty Organization exercise (response category: 92.5%; acute radiation syndrome: 95.8%; hospitalization: 96.3%). PMID- 29787429 TI - First Insights Into the M2 Inflammatory Response After Adipose-Tissue-Derived Stem Cell Injections in Radiation-Injured Muscles. AB - The cutaneous radiation syndrome is the clinical consequence of local high-dose irradiation. It is characterized by extensive inflammation, necrosis, and poor revascularization of the skin, resulting in muscle inflammation and fibrosis. Based on these physiopathological processes, subcutaneous injections of adipose tissue-derived stem/stromal cells have shown favorable effects on skin-wound healing in a minipig model of cutaneous radiation syndrome, in which muscle fibrosis persisted. Since fibrosis is mainly due to the inflammatory processes that often affect underlying tissues as well, the beneficial effects of intramuscular injections of adipose-tissue-derived stem/stromal cells on tissue recovery were evaluated. The polarization of the inflammatory response of irradiated muscle in a minipig model of cutaneous radiation syndrome was determined after acute local irradiation with 50 Gy gamma rays in a preliminary study (six minipigs). Analysis of the main inflammatory cytokines of the inflammatory response M1 (IL-1-beta and IL-6) and M2 (IL-10 and TGF-beta) by western blotting and in situ hybridization, as well as analysis of CD80/CD206 M1/M2 macrophage-specific markers by immunohistochemistry on minipig muscle samples, was performed 76 d after irradiation. The treatment of irradiated muscles with autologous adipose-tissue-derived stem/stromal cells led to an increase in IL-10 and TGF-beta, being associated with an increase in CD68+/CD206+ cells in this area. This highlights a polarization of M2 in the inflammatory response and indicates that adipose-tissue-derived stem/stromal cells may direct the irradiated tissues' inflammatory response towards a proregenerative outcome. PMID- 29787431 TI - Rapid Response, Dose Assessment, and Clinical Management of a Plutonium contaminated Puncture Wound. AB - Internalization of radionuclides occurs not only by inhalation, ingestion, parenteral injection (i.e., administration of radioactive material for a medical purpose), and direct transdermal absorption, but also by contaminated wounds. In June 2010, a glove-box operator at the U.S. Department of Energy's Savannah River Site sustained a puncture wound while venting canisters containing legacy materials contaminated with Pu. To indicate the canisters had been vented, a flag was inserted into the vent hole. The shaft of the flag penetrated the protective gloves worn by the operator. Initial monitoring performed with a zinc-sulfide alpha detector indicated 300 dpm at the wound site. After being cleared by radiological controls personnel, the patient was taken to the site medical facility where decontamination was attempted and diethylenetriaminepentaacetic acid (DTPA) was administered intravenously within 1.5 h of the incident. The patient was then taken to the Savannah River Site In Vivo Counting Facility where the wound was counted with a Canberra GL 2820 high-purity germanium detector, capable of quantifying contamination by detecting low-energy x rays and gamma rays. In addition to the classic 13, 17, and 20 keV photons associated with Pu, the low-yield (0.04%) 43.5 keV peak was also detected. This indicated a level of wound contamination orders of magnitude above the initial estimate of 300 dpm detected with handheld instrumentation. Trace quantities of Am were also identified via the 59.5 keV peak. A 24 h urine sample collection was begun on day 1 and continued at varying intervals for over a year. The patient underwent a punch biopsy at 3 h postincident (14,000 dpm removed) and excisional biopsies on days 1 and 9 (removal of an additional 3,200 dpm and 3,800 dpm, respectively). The initial post-DTPA urine sample analysis report indicated excretion in excess of 24,000 dpm Pu. Wound mapping was performed in an effort to determine migration from the wound site and indicated minimum local migration. In vivo counts were performed on the liver, axillary lymph nodes, supratrochlear lymph nodes, and skeleton to assess uptake and did not indicate measurable activity. Seventy-one total doses of DTPA were administered at varying frequencies for 317 d post intake. After allowing 100 d for removal of DTPA from the body, five 24 h urine samples were collected and analyzed for dose assessment by using the wound model described in National Council on Radiation Protection and Measurements Report No. 156. The total effective dose averted via physical removal of the contaminant and DTPA administration exceeded 1 Sv, demonstrating that rapid recognition of incident magnitude and prompt medical intervention are critical for dose aversion. PMID- 29787432 TI - PEGylated IL-11 (BBT-059): A Novel Radiation Countermeasure for Hematopoietic Acute Radiation Syndrome. AB - Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin-11. A single dose of 1.2 mg kg of BBT-059, administered subcutaneously to CD2F1 mice (12-14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to Co gamma total-body irradiation. A single dose of 0.3 mg kg, administered either 24 h pre , 4 h post-, or 24 h postirradiation increased the survival of mice to 70-100% from lethal doses of radiation. Preadministration (-24 h) of the drug conferred a significantly (p < 0.05) higher survival compared to 24 h post-total-body irradiation. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pretreated with BBT 059. The drug also increased bone marrow cellularity and megakaryocytes and accelerated multilineage hematopoietic recovery. In addition, BBT-059 inhibited the induction of radiation-induced hematopoietic biomarkers, thrombopoietin, erythropoietin, and Flt-3 ligand. These results indicate that BBT-059 is a promising radiation countermeasure, demonstrating its potential to be used both pre- and postirradiation for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event. PMID- 29787433 TI - Investigation of Spatial Organization of Chromosome Territories in Chromosome Exchange Aberrations After Ionizing Radiation Exposure. AB - Higher-order organization of the human genome is well established with chromosomes occupying distinct domains or territories in the interphase nucleus. Spatial organization of chromosome territories in the interphase nucleus occurs in a cell-type-specific manner. Since both stable and unstable aberrations induced by ionizing radiation involve the exchange of material between two or more chromosomes, this study investigated the role of spatial organization of chromosome domains in ionizing-radiation-induced chromosome translocation events. Using multicolor fluorescence in situ hybridization, the study characterized the positioning of each human chromosome relative to its neighborhood territories in the interphase nucleus of lymphocytes and B-lymphoblastoid cells before ionizing radiation and compared this interphase positioning with the spectrum of exchanges observed after ionizing radiation in the metaphase chromosomes. In addition to multicolor fluorescence in situ hybridization, the genome-wide chromosome conformation capture technique (Hi-C) was also performed in mock and x-ray irradiated human B-lymphoblastoid and fibroblast cells to characterize the interactions among chromosomes and to assess the genome reorganization changes, if any, after ionizing radiation exposure. On average, 35-50% of the total translocations induced by x rays and neutrons correlated with proximity of chromosome territories detected by multicolor fluorescence in situ hybridization in both lymphocytes and lymphoblastoid cells. The translocation rate observed in proximally positioned chromosome territories was consistently higher than distally located territories and was found to be statistically significant (p = 0.01) in human lymphoblastoid cells after x rays. The interchromosome interaction frequencies detected by Hi-C correlate fairly well with ionizing-radiation induced translocations detected by multicolor fluorescence in situ hybridization, suggesting the importance of chromosome proximity effects in ionizing-radiation induced chromosomal translocation events. PMID- 29787435 TI - NHEJ Contributes to the Fast Repair of Radiation-induced DNA Double-strand Breaks at Late Prophase I Telomeres. AB - Exposure of cells to ionizing radiation induces DNA double-strand breaks. To repair double-strand breaks correctly, cells must distinguish between the ends of chromosomes (telomeres) and DNA double-strand breaks within chromosomes. Double strand breaks in telomeric DNA may lead to telomere shortening and mutagenesis. Eukaryotic cells repair double-strand breaks primarily by two mechanisms: error free homologous recombination and error-prone nonhomologous end joining, of which homologous recombination is used in early meiotic prophase I to create recombined haploid gametes by two meiotic cell divisions lacking an intervening S-phase. Genotoxic exposures put meiosis at risk to transmit mutations, and ionizing radiation is known to induce large double-strand break-marking phospho (gamma) H2AX foci along the cores and ends of mouse meiotic chromosomes. However, it remained unclear through which repair pathway the ionizing radiation-induced telomeric double-strand breaks are repaired in late prophase I spermatocytes. Using male wild-type and nonhomologous end joining-deficient (severe combined immunodeficient) mice, this study investigated the kinetics of in vivo double strand break formation and repair at telomeres of late prophase I chromosomes up to 12 h after 0.5 Gy of whole-body gamma irradiation. Late pachytene and diplotene spermatocytes revealed overlapping gamma-H2AX and telomere repeat signal foci, indicating telomeric DNA damage. The comparison of double-strand break repair rates at telomeres and internal prophase chromosome sites revealed a more rapid double-strand break repair at wild-type telomeres during the first hour after irradiation. Increased double-strand break foci numbers at nonhomologous end joining-deficient telomeres and chromosomes and a slowed repair rate in this DNA-dependent protein kinase catalytic subunit mutant suggest that the fast repair of double-strand breaks in telomeric DNA repeats during late prophase I is largely mediated by canonical nonhomologous end joining. PMID- 29787434 TI - Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers. AB - For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose- and time dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes. PMID- 29787436 TI - Immunological Markers of Chronic Occupational Radiation Exposure. AB - This study aimed to identify immunological biomarkers for prolonged occupational radiation exposure and thus studied a random sample of the Mayak Production Association worker cohort (91 individuals). The control group included 43 local individuals never employed at the Mayak Production Association. To identify biomarkers, two groups of workers were formed: the first one included workers chronically exposed to external gamma rays at cumulative doses of 0.5-3.0 Gy (14 individuals); the second one included workers exposed to combined radiation external gamma rays at doses ranging from 0.7 to 5.1 Gy and internal alpha radiation from incorporated plutonium with 0.3-16.4 kBq body burden (77 individuals). The age range of the study individuals was 66-91 y. Peripheral blood serum protein concentrations of cytokines, immunoglobulins, and matrix metalloproteinase-9 were analyzed using enzyme-linked immunoassay following the manufacturer's protocol. Flow cytometry was used to analyze levels of various lymphocyte subpopulations. The findings of the current study demonstrate that some immunological characteristics may be considered as biomarkers of prolonged chronic radiation exposure for any radiation type (in the delayed period after the exposure) based on fold differences from controls: M immunoglobulin fold differences were 1.75 +/- 0.27 (p = 0.0001) for external gamma-ray exposure and 1.50 +/- 0.27 (p = 0.0003) for combined radiation exposure; matrix metalloproteinase-9 fold differences were 1.5 +/- 0.22 (p = 0.008) for external gamma-ray exposure and 1.69 +/- 0.24 (p = 0.00007) for combined radiation exposure; A immunoglobulin fold differences were 1.61 +/- 0.27 (p = 0.002) for external gamma-ray exposure and 1.56 +/- 0.27 (p = 0.00002) for combined radiation exposure; relative concentration of natural killer cell fold differences were 1.53 +/- 0.23 (p = 0.01) for external gamma-ray exposure and 1.35 +/- 0.22 (p = 0.001) for combined radiation exposure; and relative concentration of T-lymphocytes fold differences were 0.89 +/- 0.04 (p = 0.01) for external gamma-ray exposure and 0.95 +/- 0.05 (p = 0.003) for combined radiation exposure. Based on fold differences from controls, interferon-gamma (3.50 +/- 0.65, p = 0.031), transforming growth factor-beta (2.91 +/- 0.389, p = 0.026), and relative blood serum levels of T-helper cells (0.90 +/- 0.065, p = 0.02) may be used as immunological markers of chronic external gamma-ray exposure. Moreover, there was a significant inverse linear association of relative concentration of T-helper cells with dose from external gamma rays accumulated over an extended period. PMID- 29787438 TI - Predicting the Public Health Consequences of a Nuclear Terrorism Attack: Drawing on The Experiences of Hiroshima and Fukushima. AB - The increasing threat of nuclear terrorism warrants consideration of the health consequences of a terrorist incident should preventive measures fail. Although there has not yet been a nuclear terrorist attack of any kind, experiences with the aftermath of the bombing of Hiroshima and the core meltdowns at Fukushima can provide useful insight and allow some inferences to be made regarding the types of casualties that might be sustained and the rescue efforts that might be required. There are many parallels between the events at Hiroshima and what might be expected from an improvised nuclear device, and there are parallels between the radioactivity released to the environment at Fukushima and the aftermath of a radiological dispersal device attack. Nevertheless, there are some unique aspects to a ground-detonated improvised nuclear device that pose health threats beyond those seen at Hiroshima (i.e., fallout). And psychological health may be impacted more than physical health in the case of a radiological dispersal device. Preparedness requires consideration of all of these various health hazards in order to determine how best to mitigate the consequences of a nuclear terrorism attack. PMID- 29787437 TI - Liquid Biopsy Using Whole Blood from Testis Tumor and Colon Cancer Patients-A New and Simple Way? AB - Tumor cells shed exosomes, which are released to the blood. Detecting tumor derived exosomes containing RNA in plasma (liquid biopsy) is currently being investigated for early identification of occult metastases or relapses. Isolation of exosomes is laborious, resulting in low RNA yields. As a more robust (but less sensitive) alternative, the authors examined whether whole blood can be used as well. Tumor samples from nonmetastasized seminoma (n = 5) and colon cancer patients (n = 6) were taken during surgery. Whole-blood samples were taken before and 5-7 d after surgery. A whole genome mRNA microarray screening was performed. Candidate genes were selected based on two criteria: (1) gene expression in the presurgical whole-blood sample/tumor biopsy; and (2) a two-fold decrease in the copy number of candidate genes was expected in the postsurgical whole-blood sample 5-7 d after intervention, relative to the presurgical blood sample. The rationale behind this is the loss of tumor material in the body and the decline in the release of tumor-derived RNA in exosomes. For both tumor entities and for each patient, several hundred candidate genes could be identified. In a group wise comparison, 20 candidate genes could be identified in the seminoma and 32 in the colon cancer group. These findings indicate that whole blood might be suitable for a liquid biopsy. However, this study identified the short period after surgery (5-7 d) as a possible confounder. The authors plan to add an additional time point several weeks after the operation to discriminate tumor candidate genes from genes induced by the surgery. PMID- 29787439 TI - Genotoxic Effects in Human Fibroblasts Exposed to Microwave Radiation. AB - In the last decades, technological development has led to an increasing use of devices and systems based on microwave radiation. The increased employment of these devices has elicited questions about the potential long-term health consequences associated with microwave radiation exposure. From this perspective, biological effects of microwave radiation have been the focus of many studies, but the reported scientific data are unclear and contradictory. The aim of this study is to evaluate the potential genotoxic and cellular effects associated with in vitro exposure of human fetal and adult fibroblasts to microwave radiation at the frequency of 25 GHz. For this purpose, several genetic and biological end points were evaluated. Results obtained from comet assay, phosphorylation of H2AX histone, and antikinetochore antibody (CREST)-negative micronuclei frequency excluded direct DNA damage to human fetal and adult fibroblasts exposed to microwaves. No induction of apoptosis or changes in prosurvival signalling proteins were detected. Moreover, CREST analysis showed for both the cell lines an increase in the total number of micronuclei and centromere positive micronuclei in exposed samples, indicating aneuploidy induction due to chromosome loss. PMID- 29787441 TI - Exome Sequencing Discloses Ionizing-radiation-induced DNA Variants in the Genome of Human Gingiva Fibroblasts. AB - Ionizing radiation can induce genomic lesions such as DNA double-strand breaks whose incomplete or faulty repair can result in mutations, which in turn can influence cellular functions and alter the fate of affected cells and organ systems. Ionizing-radiation-induced sequence alterations/mutations occur in a stochastic manner, which contributes to an increased cancer risk in irradiated individuals. Ionizing radiation exposure, and particularly acute doses at high dose rates (as often observed in radiation accidents), induce alterations in the genome that in part will reflect specific characteristics of the DNA damage response and the repair mechanisms involved. Here, the exome of primary human gingival fibroblasts not exposed or exposed to 0.2, 2, 5, or 10 Gy of x rays was investigated after 16 h of DNA repair for ionizing-radiation-induced mutations. The irradiation effect with varying dose was investigated using three different bioinformatic filters for the analysis of accumulated variants per Mb of genomic DNA and per cytogenetic bands. A highly stringent cutoff of 20-fold coverage was used for all analyses. Comparing exome DNA from irradiated and nonirradiated cells disclosed a characteristic variation of the frequency of ionizing-radiation induced single-nucleotide variants as well as small insertions and deletions among chromosomes and their subregions. Increases in ionizing-radiation-induced variants with increasing dose were highly significant (p = 2.2 * 10, Kruskal Wallis test). These results indicate that certain chromosomal regions may be more prone to accumulating particular ionizing-radiation-induced alterations than others, which points to a characteristic metasignature in the irradiated exome. PMID- 29787440 TI - Developments in Biodosimetry Methods for Triage With a Focus on X-band Electron Paramagnetic Resonance In Vivo Fingernail Dosimetry. AB - Instrumentation and application methodologies for rapidly and accurately estimating individual ionizing radiation dose are needed for on-site triage in a radiological/nuclear event. One such methodology is an in vivo X-band, electron paramagnetic resonance, physically based dosimetry method to directly measure the radiation-induced signal in fingernails. The primary components under development are key instrument features, such as resonators with unique geometries that allow for large sampling volumes but limit radiation-induced signal measurements to the nail plate, and methodological approaches for addressing interfering signals in the nail and for calibrating dose from radiation-induced signal measurements. One resonator development highlighted here is a surface resonator array designed to reduce signal detection losses due to the soft tissues underlying the nail plate. Several surface resonator array geometries, along with ergonomic features to stabilize fingernail placement, have been tested in tissue-equivalent nail models and in vivo nail measurements of healthy volunteers using simulated radiation induced signals in their fingernails. These studies demonstrated radiation induced signal detection sensitivities and quantitation limits approaching the clinically relevant range of <= 10 Gy. Studies of the capabilities of the current instrument suggest that a reduction in the variability in radiation-induced signal measurements can be obtained with refinements to the surface resonator array and ergonomic features of the human interface to the instrument. Additional studies are required before the quantitative limits of the assay can be determined for triage decisions in a field application of dosimetry. These include expanded in vivo nail studies and associated ex vivo nail studies to provide informed approaches to accommodate for a potential interfering native signal in the nails when calculating the radiation-induced signal from the nail plate spectral measurements and to provide a method for calibrating dose estimates from the radiation-induced signal measurements based on quantifying experiments in patients undergoing total-body irradiation or total-skin electron therapy. PMID- 29787442 TI - Epidemiology of Late Health Effects in Ukrainian Chornobyl Cleanup Workers. AB - This article summarizes the results of 30 y of follow-up of cancer and noncancer effects in Ukrainian cleanup workers after the Chornobyl accident. The number of power plant employees and first responders with acute radiation syndrome under follow-up by the National Research Center for Radiation Medicine decreased from 179 in 1986-1991 to 105 in 2011-2015. Cancers and leukemia (19) and cardiovascular diseases (21) were the main causes of deaths among acute radiation syndrome survivors (54) during the postaccident period. Increased radiation risks of leukemia in the Ukrainian cohort of 110,645 cleanup workers exposed to low doses are comparable to those among survivors of the atomic bomb explosions in Japan in 1945. Additionally, an excess of chronic lymphocytic leukemia was demonstrated in the cleanup workers cohort for 26 y after the exposure. A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. High prevalence was demonstrated for cardio- and cerebrovascular diseases and mental health changes. However, the reasons for the increases require further investigation. To monitor other possible late effects of radiation exposure in Chornobyl cleanup workers, analytical cohort and case-control studies need to include cardiovascular pathology, specifically types of potentially radiogenic cancers using a molecular epidemiology approach. Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology. PMID- 29787443 TI - Old Data-New Concepts: Integrating "Indirect Effects" Into Radiation Protection. AB - PURPOSE: To address the following key question, what are the consequences of nontargeted and delayed effects for linear nonthreshold models of radiation risk? This paper considers low-dose "indirect" or nontargeted effects and how they might impact radiation protection, particularly at the level of the environment. Nontargeted effects refer to effects in cells, tissues, or organisms that were not targeted by irradiation and that did not receive direct energy deposition. They include genomic instability and lethal mutations in progeny of irradiated cells and bystander effects in neighboring cells, tissues, or organisms. Low-dose hypersensitivity and adaptive responses are sometimes included under the nontargeted effects umbrella, but these are not considered in this paper. Some concepts emerging in the nontargeted effects field that could be important include historic dose. This suggests that the initial exposure to radiation initiates the instability phenotype which is passed to progeny leading to a transgenerational radiation-response phenotype, which suggests that the system response rather than the individual response is critical in determining outcome. CONCLUSION: Nontargeted effects need to be considered, and modeling, experimental, and epidemiological approaches could all be used to determine the impact of nontargeted effects on the currently used linear nonthreshold model in radiation protection. PMID- 29787444 TI - French Policies for Victim Management During Mass Radiological Accidents/Attacks. AB - In the current international context, emergency medical services have to be prepared for chemical, biological, radiological, and nuclear events. Emergency response to radiological or nuclear events requires coordination between many components: the fire brigade, emergency medical services (including nurses and physicians), police, hospitals, etc. To optimize efficiency, victim management in France is governed by specific policies and planned responses. This plan for radiological/nuclear event response is inspired by military chemical, biological, radiological, and nuclear victim management in the operational theatre and is based on extraction (removal to a safe environment), first triage, decontamination, second triage, treatment, substance identification, and training. It is also supported by specific equipment. Prehospital victim management in case of nuclear and radiological accident or attack will be described, as well as French-specific supplies. This response plan is constantly evolving due to the complexity of radiological and nuclear events. PMID- 29787448 TI - A Model for Sustaining NCLEX-RN Success. AB - Beginning in 2013, an individualized National Council Licensure Exam (NCLEX-RN) study process with follow through postgraduation was initiated to achieve benchmark pass rates in a nursing program where pass rates had dropped. Identification of students at risk for NCLEX failure and using resources available through an integrated testing program led to the implementation of an individualized NCLEX preparation process. Since implementation, first-time pass rates exceeded the national norm for baccalaureate test takers by 5.41 percent to 11.5 percent for four consecutive years. This model can be used by schools of nursing to guide students in NCLEX preparation. PMID- 29787445 TI - Deployment of the DosiKit System Under Operational Conditions: Experience From a French Defense National Nuclear Exercise. AB - Estimation of the dose received by accidentally irradiated victims is based on a tripod: clinical, biological, and physical dosimetry. The DosiKit system is an operational and mobile biodosimetry device allowing the measurement of external irradiation directly on the site of a radiological accident. This tool is based on capillary blood sample and hair follicle collection. The aim is to obtain a whole-body and local-surface dose assessment. This paper is about the technical evaluation of the DosiKit; the analytical process and scientific validation are briefly described. The Toulon exercise scenario was based on a major accident involving the reactor of a nuclear attack submarine. The design of the scenario made it impossible for several players (firefighters, medical team) to leave the area for a long time, and they were potentially exposed to high dose rates. The DosiKit system was fully integrated into a deployable radiological emergency laboratory, and the response to operational needs was very satisfactory. PMID- 29787449 TI - Functional connectivity during monitoring for visuomotor incongruence. AB - Previous human studies on monitoring for visuomotor incongruence emphasized the contribution of the fronto-parietal network and revealed significant activation of the right dorsolateral prefrontal cortex (DLPFC) and the right rostral inferior parietal lobule. Using functional MRI, this study investigated the brain regions involved in explicit monitoring for incongruence between motor intention and visual and/or proprioceptive information, particularly focusing on the fronto parietal network. During in-phase bimanual movements, a static image of the participant's own hands was randomly inserted within real-time visual feedback of the movements to produce a mismatch between the actual performance and the visual input. The results of our task were similar to those of previous studies, in that greater activity was observed in the right DLPFC during incongruence conditions than during congruence conditions. However, the anatomical location of the DLPFC cluster was found in a more ventral region, compared with previous studies. Psychophysiological interaction analysis for the entire brain, using the right DLPFC as a seed region, indicated significantly greater functional connectivity with the bilateral dorsal premotor cortex, middle temporal gyri (area V5), and right rostral inferior parietal lobule (area PFt). PMID- 29787450 TI - Cannabinoids in the Management of Musculoskeletal Pain: A Critical Review of the Evidence. PMID- 29787452 TI - Message From the Editor. PMID- 29787451 TI - Wide-Awake Hand Surgery: Principles and Techniques. PMID- 29787453 TI - Information Reception and Expectations Among Hospitalized Elderly Patients in Taiwan: A Pilot Study. AB - BACKGROUND: Communicating with patients, especially geriatric patients, is a challenge for medical professionals. Medical message receiving and expectations among hospitalized elderly patients have not been studied. PURPOSE: The aim of this study was to explore medical message receiving and expectations concerning medical information among hospitalized elderly patients in Taiwan. METHODS: A descriptive study design was used. Convenience sampling was applied, and the research was conducted in a geriatric ward in a medical center in southern Taiwan. Patients were recruited who were 65 years or older and capable of verbal communication. Data were collected using a self-developed semistructured questionnaire. For each participant, data were collected in one regular ward round. The messages of the physician were recorded. During the first and fourth hours after the ward round, the researcher collected the medical messages that were conveyed by the physician in the ward round and that could be repeated by the patients. Open-ended questions were used to collect data about patient expectations of medical messages during the first hour after the ward round. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using content analysis. RESULTS: Thirty patients participated in this study. All of the participants remembered the visit of the physician. Seventeen participants (56.6%), however, could not repeat the messages, and the total message repetition rate was 17.8% at the first hour after the ward round. By the fourth hour, the message repetition rate fell to 8.9%. Furthermore, three participants (10%) reported messages incorrectly. Participants reported the importance and necessity of physicians conveying medical messages. "Desire to know the reasons for discomfort" and "discharge date" were the messages most expected by the participants. CONCLUSIONS: This study suggests that most hospitalized elderly patients cannot repeat medical messages that are conveyed by their physicians. Written materials and the involvement of principal caregivers in the medical informing process may be necessary. Besides, before providing medical information, medical professionals should be cognizant of the key concerns of their patients. PMID- 29787454 TI - Moving Patient Safety Into Ambulatory Settings and Beyond. PMID- 29787455 TI - A National Report of Nursing Home Quality and Information Technology: Two-Year Trends. PMID- 29787456 TI - Fecal Microbial Transplant in Children With Ulcerative Colitis: A Randomized, Double Blinded, Placebo-Controlled Pilot Study: Retraction. PMID- 29787457 TI - Threshold Concepts in Doctoral Education: A Framework for Writing Development in Novice Nurse Scientists. AB - Pedagogical practices for writing development in doctoral programs are often the by-product of completing dissertation research and may lack deliberate strategies to assist students with complex genres of writing. This article proposes a framework for doctoral education to assist students with mastery of threshold concepts in writing. Threshold concepts in writing are examined for their applicability to the evolution of writing in PhD nursing students as they begin to think and write like nurse scientists. PMID- 29787459 TI - Effects of Faculty Development and Computerized Learning and Assessment Tools on Testing Outcomes. PMID- 29787458 TI - Peer Teaching in High-Fidelity Simulation: Participant Experiences and Reflections. AB - Peer teaching provides students with opportunities to experience the educator role and increase self-confidence and problem-solving skills. To address the shortage of meaningful leadership experiences for senior baccalaureate nursing students, faculty implemented an alternative leadership experience involving senior students taking on the role of peer teachers in the high-fidelity simulation (HFS) laboratory. We conducted focus groups to assess peer teachers and learners' experiences and used thematic analysis to examine and interpret the data. Findings included the intersection of learning, HFS, clinical experience, and teaching; the benefits of practicing teaching in a safe environment; how empathy enhanced understanding of the continuum of expertise; and power differentials experienced by peer teachers and learners. PMID- 29787460 TI - Unmet information needs of patients with melanoma in Germany. AB - There is a scarcity of available data on unmet information needs (UINs) of melanoma patients (MPs) from Germany and of MPs with clinical stage IV. In a multicenter cross-sectional survey, we explored the UINs of 529 MPs by applying a standardized questionnaire. Subgroup differences in scope and contents of UINs were determined by univariate analyses. Predictors of the presence of UINs were identified by binary logistic regression. Overall, 55% of MPs reported UINs. Most MPs felt poorly or not informed about psychosocial support (24-31%). In MPs currently receiving medical treatment [odds ratio (OR): 1.9; P=0.017], MPs aging of at least 55 years (OR: 1.7; P=0.029), and in MPs who generally had a high need for information on their condition (OR: 2.4; P=0.001), the presence of UINs was significantly more likely than in post-treatment MPs, MPs more than 55 years of age, and those whose general information need was low. Most UINs concerned treatment-related information and were reported by MPs with tumor progression. Presence and scope of UINs did not differ significantly between metastatic and nonmetastatic MPs (57 vs. 53%; P=0.436). We highlighted differences in the presence, scope, and contents of UINs between MP subgroups, which should be considered when educating them in medical consultations and providing information via media. In particular, MPs felt insufficiently informed about psychosocial support and desired more treatment information. PMID- 29787461 TI - Cost-effectiveness of Routine Postoperative Retrograde Voiding Trials Following Pelvic Surgeries. AB - OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of retrograde voiding trials in the management of postoperative voiding dysfunction. METHODS: We developed a disease simulation model to assess under which conditions routine retrograde voiding trial is the optimal strategy in terms of cost per quality-adjusted life-year and cost per case of chronic voiding dysfunction avoided. We varied the incidence of voiding dysfunction between 2% and 60%. We discounted future costs and utilities at 3% annually. We conducted 1- and 2-way sensitivity analyses on uncertain model parameters. RESULTS: The lifetime analysis showed that when the incidence of postoperative voiding dysfunction exceeded 12.2%, retrograde voiding trials were cost-effective, assuming a willingness-to-pay (WTP) for health of $100,000/quality-adjusted life-year. When the incidence exceeded 31.1%, retrograde voiding trials became the dominant strategy (less costly and more effective). For a simple hysterectomy with voiding dysfunction incidence of approximately 10%, lifetime cost is $230,069/case of chronic voiding dysfunction avoided; for a midurethral sling with voiding dysfunction incidence of approximately 20%, lifetime cost is $60,449/case avoided. Sensitivity analyses showed that WTP for health, the incidence of presentation to the emergency department (ED) for urinary retention and the incidence of chronic urinary retention following treatment in the ED had the greatest impact on the cost-effectiveness results. CONCLUSIONS: Routine retrograde voiding trials following pelvic surgery can be cost-effective compared with expectant management when the incidence of voiding dysfunction exceeds 12.2%. These results were sensitive to WTP for health, incidence of ED visits for urinary retention, and incidence of chronic urinary retention following ED visits. PMID- 29787462 TI - Current Role of Urethrolysis and Partial Excision in Patients Seeking Revision of Anti-Incontinence Sling. AB - OBJECTIVES: Stress urinary incontinence is highly prevalent and sling surgery has increased since 2000. Urethrolysis traditionally had been standard management of complications after anti-incontinence surgery; however, partial excision is a less aggressive option. This study describes the different populations in a contemporary cohort that undergo sling excision and urethrolysis and their surgical outcomes. METHODS: Chart analysis was performed on patients assigned Current Procedural Terminology codes for removal or revision of sling for stress incontinence, urethrolysis, or revision of graft at our institution from 2010 to 2015. Demographics, indications, outcomes, and subsequent treatment were evaluated. RESULTS: A total of 110 patients underwent surgery and were included. Partial excision was performed on 82 patients and urethrolysis on 28 patients. About 32.7% had prior revision, and median length to revision was 3.1 years. Overall success was 75.0% for urethrolysis and 86.6% for partial excision. Without concomitant sling placement, stress incontinence developed in 25.0% of urethrolysis and 21.6% of partial excision patients. New onset overactive bladder symptoms developed in 21.4% of urethrolysis patients and 7.3% of partial excision, which was significantly different (P = 0.039). CONCLUSIONS: Both approaches had good success, 75.0% for formal urethrolysis and 86.6% for partial excision. New onset urgency was lower for partial excision, but rates of all other complications were similar. These procedures are often used for different patient populations, and thus, outcomes are not meant to be directly compared. Future work on sling revision should report these procedures separately. PMID- 29787463 TI - Lateral Patellar Instability in the Skeletally Mature Patient: Evaluation and Surgical Management. AB - Lateral patellar instability is a common disease process that affects all types of patients. Depending on the patient's anatomy and the results of preoperative imaging, surgical management options include medial patellofemoral ligament reconstruction, tibial tubercle osteotomy, and sulcus-deepening trochleoplasty. Medial patellofemoral ligament reconstruction or repair is useful for almost all patients, whereas tibial tubercle osteotomy is helpful to correct a lateralized tibial tubercle and the associated elevated lateral pull of the extensor mechanism. For a select subset of patients with severe trochlear dysplasia, a sulcus-deepening trochleoplasty can be a useful option to prevent future patellar instability. Many technical considerations exist for each procedure, and in most situations, no consensus exists to direct surgeons on the superior technique. PMID- 29787464 TI - Costs and Radiographic Outcomes of Rotational Ankle Fractures Treated by Orthopaedic Surgeons With or Without Trauma Fellowship Training. AB - INTRODUCTION: We evaluated the radiographic outcomes and surgical costs of surgically treated rotational ankle fractures in our health system between providers who had completed a trauma fellowship and those who had not. METHODS: We grouped patients into those treated by trauma-trained orthopaedic surgeons (TTOS) and non-trauma-trained orthopaedic surgeons (NTTOS). We graded the quality of fracture reductions and calculated implant-related costs of treatment. RESULTS: A total of 208 fractures met the inclusion criteria, with 119 in the TTOS group and 89 in the NTTOS group. Five patients lost reduction during the follow-up period. The adequacy of fracture reduction at final follow-up did not differ (P = 0.29). The median surgical cost was $2,940 for the NTTOS group and $1,233 for the TTOS group (P < 0.001). DISCUSSION: We found no notable differences in radiographic outcomes between the TTOS and NTTOS groups. Cost analysis demonstrated markedly higher implant-related costs for the NTTOS group, with the median surgical cost being more than twice that for the TTOS group. LEVEL OF EVIDENCE: Level III. PMID- 29787465 TI - PREDICTIVE FACTORS FOR PROLIFERATIVE VITREORETINOPATHY FORMATION AFTER UNCOMPLICATED PRIMARY RETINAL DETACHMENT REPAIR. AB - PURPOSE: To determine predictive factors of proliferative vitreoretinopathy (PVR) formation after uncomplicated primary retinal detachment repair. METHODS: Retrospective, single-center, case-control study of 74 consecutive patients with (37 eyes) and without (37 eyes) PVR formation after undergoing uncomplicated primary surgery for retinal detachment repair. Logistic regression was used to assess factors associated with PVR formation. RESULTS: Retinal detachment involving the macula was 4.2 times (adjusted odds ratio; 95% confidence interval, 1.4-12.9; P = 0.0119) more likely to have PVR formation compared with those without. Patients who were current or former smokers were 3.6 times (adjusted odds ratio; 95% confidence interval, 1.1-11.7; P = 0.0352) more likely to have PVR formation compared with nonsmokers. Compared with 25-gauge (g) vitrectomy, larger gauge vitrectomy (20 g or 23 g) was 3.6 times (adjusted odds ratio; 95% confidence interval, 1.2-11.3; P = 0.0276) more likely to have PVR formation. Duration of retinal detachment symptoms, high myopia, lens status, lattice degeneration, location of retinal break, number of retinal breaks, and surgical technique (e.g., scleral buckle with or without vitrectomy versus vitrectomy alone) were not found to be predictive of PVR formation. CONCLUSION: Cigarette smoking and macular involvement are significant risk factors predictive of PVR formation after uncomplicated primary retinal detachment repair. PMID- 29787466 TI - Dactylitis as the Presenting Manifestation of Congenital Syphilis in an Infant. PMID- 29787467 TI - Historical and Current Trends in the Epidemiology of Early Syphilis in San Francisco, 1955 to 2016. AB - BACKGROUND: Seventeen years into a sustained epidemic, early syphilis (ES) rates in San Francisco (SF) are continuing to increase and the demographics of the affected population are changing. We provide a historical overview of ES in SF among men who have sex with men (MSM) and describe trends in the epidemiology and disease investigation outcomes. METHODS: We examined data from the SF Department of Public Health's patient-based registry of integrated STD surveillance, clinical, and field investigation data to describe demographic and behavioral characteristics of ES cases, as well as outcomes of syphilis partner services (PS). chi Tests were performed to examine categorical differences across periods. Analysis of variance was used to examine differences in continuous variables. RESULTS: In 2016, 1095 ES cases were reported among males in SF, a 219% increase from the 343 cases identified 10 years ago. Between 1996-1999 and 2010-2016, an increasing proportion of ES cases were among MSM younger than 25 years, nonwhite, and HIV negative (P < 0.05). A decreasing proportion of ES cases were assigned for PS, among whom a smaller proportion of reported sex partners were identified by name, resulting in an overall decline in the proportion of cases who had at least one named partner treated as a result of PS (Disease Intervention Rate) from 30.5 in 2000-2004 to 14.8 in 2010-2016. CONCLUSIONS: Syphilis case rates continue to increase in SF and the epidemic is expanding beyond a core population. Additional resources and innovative prevention approaches are needed to reduce the burden of syphilis among MSM. PMID- 29787468 TI - Cortical Thickness Alterations in Chronic Pain Disorder: An Exploratory MRI Study. AB - OBJECTIVE: Chronic pain disorder (CPD) has been associated with brain changes, especially in limbic circuits. However, in most patients with chronic pain, depression or anxiety is a common comorbidity. In this exploratory and naturalistic study, we investigated brain cortical thickness (CTh) differences between patients with CPD and healthy controls, with consideration of concurrent psychiatric symptoms. METHODS: Twenty-three patients with CPD and 23 age- and sex matched healthy volunteers were included in this study. CTh was estimated using Freesurfer on high-resolution three-dimensional T1-weighted images acquired with a 3T scanner. Group differences were investigated using an analysis of covariance model that included age, sex, and Beck Depression Inventory I and Trait Anxiety Inventory scores as covariates. The relationship between CTh and Toronto Alexithymia Scale (TAS-20) scores was also investigated in patients. Data were corrected for multiplicity using the False Discovery Rate approach (q < .05). RESULTS: The comparison between groups using demographics and Beck Depression Inventory I scores as covariates showed thinner cortex in patients compared with controls, after correction for multiplicity in the left precentral (F(1,42) = 21.9, p < .05) and postcentral gyri (F(1,42) = 26.9, p < .05) and in the left inferior temporal sulcus (F(1,42) = 19.6, p < .05). Moreover, using the Trait Anxiety Inventory as covariate, a trend toward significance (p < .001 uncorrected) was seen for the left precentral gyrus (F(1,42) = 13.8), right middle frontal (F(1,42) = 14.3) and inferior parietal gyri (F(1,42) = 13.4), and right anterior temporal pole (F(1,42) = 15.9). CONCLUSIONS: The results indicate that brain morphological differences between patients with chronic pain disorder and healthy controls are localized to regions that correspond to sensory as well as affective dimensions of pain processing. PMID- 29787469 TI - Changes in Blood Pressure After the 2016 United States Presidential Election. Analyses in Response to "The Association of Posttraumatic Stress Disorder With Clinic and Ambulatory Blood Pressure in Healthy Adults" by Edmondson et al. PMID- 29787470 TI - Importance of being collaborative for return to work with back pain. PMID- 29787471 TI - Hemisensory disturbances in patients with complex regional pain syndrome. AB - Sensory disturbances often spread beyond the site of injury in complex regional pain syndrome (CRPS) but whether this applies equally to CRPS I and II, or changes across the course of the disease, is unknown. Establishing this is important, because different symptom profiles in CRPS I and II, or in acute vs chronic CRPS, might infer different pathophysiology and treatment approaches. To explore these questions, sensory disturbances were assessed in the limbs and forehead of 71 patients with CRPS I and 33 patients with CRPS II. Pain had persisted up to 12 months in 32 patients, for 13 to 36 months in 29 patients, and for longer than this in 43 patients. Patients with CRPS I were more likely to be female, and pain was more likely to be present in an additional limb, than patients with CRPS II. Conversely, pain was more likely to be associated with sensory deficits and allodynia in patients with CRPS II than CRPS I. Nevertheless, heightened sensitivity, allodynia, and/or hyperalgesia to mechanical and thermal stimuli were detected in a hemisensory distribution ipsilateral to the affected limb in both forms of CRPS. Some of these hemisensory disturbances strengthened with chronicity of pain. These findings suggest that heightened excitability of nociceptive pathways in CRPS spreads to hemisensory convergence points in the brainstem or higher brain centres, possibly in association with compromised pain controls. The similarity of symptom profiles in chronic CRPS I and II implies shared mechanisms despite different triggers. PMID- 29787472 TI - A randomised, placebo-controlled clinical trial with the alpha2/3/5 subunit selective GABAA positive allosteric modulator PF-06372865 in patients with chronic low back pain. AB - The effect of PF-06372865, a subtype-selective positive allosteric modulator of the gamma-aminobutyric acid type A (GABAA) receptor, on chronic low back pain was investigated in a randomised, placebo- and active-controlled phase 2 clinical trial. The parallel treatment group trial consisted of a 1-week single-blind placebo run in the phase, followed by 4-week double-blind treatment. Patients were randomised to receive either PF-06372865, naproxen, or placebo twice a day for 4 weeks. The primary end point was the numerical rating score of low back pain intensity after 4 weeks of active treatment. Secondary end points included the Roland Morris Disability Questionnaire and the Hopkins Verbal Learning Test Revised. The trial had predefined decision rules based on the probability that PF 06372865 was better than placebo. The study was stopped at the interim analysis for futility. At this time, a total of 222 patients were randomised and the mean PF-06372865 4-week response on the low back pain intensity was 0.16 units higher (worse) than placebo (90% confidence interval -0.28 to 0.60). There were small, statistically significant reductions in the delayed recall test score with PF 06372865, as measured by Hopkins Verbal Learning Test-Revised. The effects of naproxen were in line with expectations. PF-06372865 was well tolerated. The most common treatment-related adverse events in the PF-06372865 arm were somnolence (5 mild and 4 moderate), dizziness (2 mild and 3 moderate), and nausea (2 mild). Although the reason for the lack of analgesic effect is not completely clear, it may be a result of not achieving sufficient receptor occupancy to drive efficacy. PMID- 29787473 TI - Factors Contributing to Medial Tibial Stress Syndrome in Runners: A Prospective Study. AB - PURPOSE: Medial tibial stress syndrome (MTSS) is one of the most common overuse injuries sustained by runners. Despite the prevalence of this injury, risk factors for developing MTSS remain unclear. The purpose of this study was to prospectively evaluate differences in passive range of motion, muscle strength, plantar pressure distributions, and running kinematics between runners who developed MTSS and those who did not. METHODS: Twenty-four National Collegiate Athletic Association Division 1 cross-country runners participated in this study. Participants underwent a clinical examination documenting passive range of motion and muscle strength at the hips and ankles. Plantar pressure analysis was used to quantify mediolateral pressure balances while walking and 3D motion capture was used to quantify running kinematics. Participants were followed up for a 2-yr period during which time any runners who developed MTSS were identified by the team's certified athletic trainer. RESULTS: Runners who developed MTSS demonstrated tighter iliotibial bands (P = 0.046; effect size [ES] = 1.07), weaker hip abductors (P = 0.008, ES = 1.51), more pressure under the medial aspect of their foot at initial foot contact (P = 0.001, ES = 1.97), foot flat (P < 0.001, ES = 3.25), and heel off (P = 0.034, ES = 1.30), greater contralateral pelvic drop (P = 0.021, ES = 1.06), and greater peak amounts (P = 0.017, ES = 1.42) and durations (P < 0.001, ES = 2.52) of rearfoot eversion during stance phase. A logistic regression (chi = 21.31, P < 0.001) indicated that every 1% increase in eversion duration increased odds of developing MTSS by 1.38 (P = 0.015). CONCLUSIONS: These findings demonstrate that the development of MTSS is multifactorial, with passive range of motion, muscle strength, plantar pressure distributions, and both proximal and distal kinematics all playing a role. We suggest that coaches or sports medicine professionals screening runners for injury risk consider adopting a comprehensive evaluation which includes all these areas. PMID- 29787475 TI - Isometric versus Dynamic Measurements of Fatigue: Does Age Matter? A Meta analysis. AB - PURPOSE: The assessment of power changes after fatiguing exercise provides important additional information about neuromuscular function compared with traditional isometric measurements, especially when exploring age-related changes in fatigability. Therefore, the aim of this review was to explore the effects of age on neuromuscular fatigue (NMF) when measured in isometric compared with dynamic contractions. The importance of central and peripheral mechanisms contributing to age-related NMF was discussed. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and SPORT Discus databases were searched. The combination of terms related to the intervention (fatiguing exercise), population (old people) and outcomes (isometric force and power) were used. This meta-analysis was registered on PROSPERO (CRD42016048389). RESULTS: Thirty-one studies were included. The meta-analyses revealed that force decrease was greater (there was more NMF) in young subjects than their older counterparts when fatigue was induced by isometric tasks (effect size [ES], 0.913; confidence interval [CI], 0.435-1.391; P < 0.001), but not when the fatiguing exercise was performed in dynamic mode (ES, 0.322; CI, -0.039 to 0.682; P = 0.08). Older individuals demonstrated a greater reduction in power after fatigue induced by either dynamic or isometric tasks (ES, -0.891; CI, -1.657 to -0.125; P = 0.023). CONCLUSIONS: There is no difference in the isometric force loss between young and old people when fatigue is induced by dynamic tasks. However, maximal power is more decreased after fatigue tasks in older adults. Thus, the assessment of fatigue (isometric force vs power) must be considered in identifying age-related NMF mechanisms. PMID- 29787474 TI - Hypothermia Decreases O2 Cost for Ex Vivo Contraction in Mouse Skeletal Muscle. AB - INTRODUCTION: Evidence suggests that the energy efficiency of key ATPases involved in skeletal muscle contractile activity is improved in a hypothermic condition. However, it is unclear how a decrease in temperature affects skeletal muscle O2 consumption (mVO2) induced by muscle contraction. METHODS: Isolated mouse extensor digitorum longus (EDL) muscles were incubated in a temperature controlled (37 degrees C or 25 degrees C) bath that included an O2 probe. EDL muscles from one limb were subjected to the measurement of resting mVO2, and the contralateral EDL muscles were used for the measurement of mVO2 with electrically stimulated contraction. For the resting protocol, muscles were suspended at resting tension for 15 min with continuous O2 recordings. For the contraction protocol, EDL muscles underwent 10 electrically stimulated isometric contractions with continuous O2 recordings for 15 min. The rate of O2 disappearance was quantified as micromoles of O2 per minute and normalized to the wet weight of the muscle. RESULTS: Resting mVO2 was greater at 37 degrees C than at 25 degrees C, consistent with the idea that lower temperature reduces basal metabolic rate. Electrically stimulated contraction robustly increased mVO2 at both 37 degrees C and 25 degrees C, which was sustained for ~3 min postcontraction. During that period, mVO2 was elevated approximately fivefold at both 37 degrees C and 25 degrees C. Greater contraction-induced mVO2 at 37 degrees C compared with 25 degrees C occurred despite lower force generated at 37 degrees C than at 25 degrees C. CONCLUSIONS: Together, O2 cost for muscle contraction (force-time integral per O2 consumed) was greater at 37 degrees C than at 25 degrees C. Levels of high-energy phosphates were consistent with greater energy demand at 37 degrees C compared with 25 degrees C. In conclusion, these results indicate that muscle contraction that occurs at subnormal temperature requires less O2 than at 37 degrees C. PMID- 29787476 TI - Maternal Physical Activity and Sex Impact Markers of Hepatic Mitochondrial Health. AB - INTRODUCTION: Maternal exercise and physical activity during the gestational period can be protective against maternal high-fat diet-induced hepatic steatosis in older offspring. However, it is unknown whether these protective effects are seen in younger offspring. In this study, we investigated whether maternal physical activity would attenuate maternal western diet (WD)-induced steatosis in young adult rats. METHODS: Female Wistar rats (7-8 wk of age) were randomized into WD (42% fat, 27% sucrose) or normal chow diet (ND), and further randomized into physical activity (RUN) or sedentary (SED) conditions for a total of four groups. Dams returned to ND/SED conditions after parturition. Postweaning, offspring were maintained in ND/SED conditions for 18 wk. RESULTS: Maternal WD induced increases in male offspring body mass was attenuated in the WD/RUN offspring (P < 0.05). Maternal WD feeding significantly increased hepatic steatosis in male (but not female offspring), which was not attenuated by maternal RUN. However, maternal RUN increased (P < 0.05) hepatic markers of mitochondrial biogenesis and mitophagy (mitochondrial transcription factor A, peroxisome proliferator activator receptor gamma, and nuclear factor E2-related factor 2) in all offspring and the mitophagy marker BCL2-interacting protein 3 in WD/RUN offspring. Interestingly, hepatic markers of de novo lipogenesis (fatty acid synthase and acetyl coenzyme A carboxylase), mitophagy (autophagy-related gene 12:5, BCL2-interacting protein 3, P62, and LC3 II/I), and mitochondria biogenesis/content (mitochondrial transcription factor A and OXPHOS-Complex II) were significantly increased in female versus male offspring. CONCLUSION: Although maternal physical activity did not attenuate maternal WD-induced hepatic steatosis as has been previously reported in older adult offspring, it did significantly increase hepatic markers of mitochondrial biogenesis and mitophagy. Furthermore, female offspring had elevated hepatic markers of mitochondrial health, possibly explaining why female rats are protected against maternal WD induced hepatic steatosis. Future studies are warranted to shed light on the time line of hepatic steatosis development under the influence of maternal physical activity. PMID- 29787477 TI - Metabolic syndrome and its components in premenopausal and postmenopausal women: a comprehensive systematic review and meta-analysis on observational studies. AB - OBJECTIVES: To perform a meta-analysis on the global prevalence of metabolic syndrome (MetS) in postmenopausal women. The meta-analysis also sought to measure the relationship menopause status has with MetS and its components. METHODS: The Web of Science, Medline, PubMed, Scopus, Embase, CINAHL, DOAJ, and Google Scholar were all searched using the relevant keywords. Articles published during the period 2004 to 2017 that met our inclusion criteria and reported the prevalence of MetS among premenopausal and postmenopausal women were included. In the presence of heterogeneity, random-effects models were used to pool the prevalence and odds ratios (ORs), as measures of association in cross-sectional and comparative cross-sectional studies, respectively. RESULTS: The prevalence of MetS among postmenopausal women (119 studies [n = 95,115]) and the OR comparing the prevalence of MetS among postmenopausal and premenopausal women (23 studies [n = 66,801]) were pooled separately. The pooled prevalence of MetS among postmenopausal women was found to be 37.17% (95% confidence interval [CI] 35.00% 39.31%), but varied from 13.60% (95% CI 13.55%-13.64%) to 46.00% (95% CI 1.90% 90.09%), depending upon the diagnostic criteria used. The overall pooled OR for MetS in postmenopausal women, compared with premenopausal women, was OR 3.54 (95% CI 2.92-4.30), but this ranged from OR 2.74 (95% CI 1.32-5.66) to OR 5.03 (95% CI 2.25-11.22), depending upon the criteria used. Furthermore, the odds of high fasting blood sugar (OR 3.51, 95% CI 2.11-5.83), low high-density lipoprotein cholesterol (OR 1.45, 95% CI 1.03-2.03), high blood pressure (OR 3.95, 95% CI 2.01-7.78), high triglycerides (OR 3.2, 95% CI 2.37-4.31), and high waist circumference (OR 2.75, 95% CI 1.80-4.21) were all found to be higher in postmenopausal women than in premenopausal women. CONCLUSIONS: The prevalence of MetS is relatively high in postmenopausal women and was more prevalent among postmenopausal than premenopausal women. Menopausal hormone therapy should be used with caution in patients with MetS, as its safety has not yet been evaluated among MetS patients and meticulous evaluation of each individual patient before starting MHT is needed. PMID- 29787478 TI - Effect of a 1-year elastic band resistance exercise program on cardiovascular risk profile in postmenopausal women. AB - OBJECTIVE: The aim of this study was to investigate the effects of a 1-year progressive resistance training program using elastic bands on cardiovascular profile parameters in sedentary postmenopausal (>12 months' amenorrhea) women. METHODS: This longitudinal prospective experimental study included 38 menopausal women who were randomly divided into two groups: an intervention group (IG, n = 18), who completed a progressive resistance training program with elastic bands over the course of 12 months (six exercises for whole body training, three sets * 10 repetitions), and a control group (CG, n = 20) that did not perform any training. Blood analysis and body composition were determined at baseline and 1 year after intervention. RESULTS: After the 1-year training program, weight, waist circumference, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein showed a decrease compared with baseline values in the IG, showing a significant (P < 0.05) improvement in cardiovascular profile. Very-low density lipoprotein, high-density lipoprotein, and triglycerides showed a nonsignificant (P > 0.05) improvement. The CG increased significantly in weight and waist circumference, whereas the rest of the variables remained unchanged. CONCLUSION: One year of progressive resistance training with elastic bands has beneficial effects on anti-inflammatory and anthropometric cardiovascular risk factors in menopausal women, including changes in lipid profile. PMID- 29787479 TI - In Reply. PMID- 29787480 TI - Evaluation and management of migraine in midlife women. AB - Migraine is highly prevalent in women and, in addition to the pain component, can be associated with significant disability and loss of productivity. Migraine is often connected to fluctuations in hormones (primarily estrogen), commonly arising in puberty, worsening in perimenopause, and quiescing in late menopause. This Practice Pearl discusses the various types of migraine with respect to hormone fluctuations and details acute as well as preventive treatment. PMID- 29787482 TI - Physical performance in relation to menopause status and physical activity. AB - OBJECTIVE: The aim of this study was to examine differences in physical performance (muscle power, muscle strength, aerobic capacity, and walking speed) across menopausal stages and potential of leisure physical activity (PA) to modify the impact of menopause on physical performance. METHODS: In this cross sectional study, women aged 47 to 55 were randomly selected from the Finnish National Registry and categorized as premenopausal (n = 233), perimenopausal (n = 381), or postmenopausal (n = 299) based on serum concentrations of follicle stimulating hormone and bleeding diary. Physical performance was measured by knee extension force, handgrip force, vertical jumping height, maximal walking speed, and 6-minute walking distance. PA level was assessed by self-report and categorized as low, moderate, or high. Multivariate linear regression modeling was used for data analysis. RESULTS: After including fat mass, height, PA, and education in the model, the postmenopausal women showed 12.0 N weaker (P < 0.001) handgrip force and 1.1 cm lower (P < 0.001) vertical jumping height than the premenopausal women. There was no significant interaction between menopausal stage and PA on physical performance. The peri- and postmenopausal women with a high PA, however, showed better performance in the maximal knee extension strength and 6-minute walking test, and showed greater lower body muscle power than those with a low PA. CONCLUSIONS: Menopause status is associated with muscle strength and power, whereas the association between menopause status and mobility/walking is clearly weaker. A high leisure PA level provides more capacity to counteract the potential negative influence of menopausal factors on muscle function. PMID- 29787483 TI - The effects of mindfulness and relaxation training for insomnia (MRTI) on postmenopausal women: a pilot study. AB - OBJECTIVE: The aim of the study was to evaluate the effects of mindfulness and relaxation training for insomnia on insomnia and quality of life in postmenopausal women. METHODS: Thirty postmenopausal women aged 50 to 65 years, who were not using hormone therapy, and had a diagnosis of insomnia and an apnea hypopnea index of less than 15, were randomly assigned to two groups: a mindfulness intervention group and a control group. They were assessed before the intervention, and 8 weeks after its completion using questionnaires assessing sleep quality (Pittsburgh Sleep Quality Index), insomnia (Insomnia Severity Index), quality of life in menopause (Menopause-Specific Quality of Life), menopausal symptoms (Kupperman Menopausal Index), and level of attention (Mindfulness Awareness Attention Scale). They were also assessed through ambulatory polysomnography. This is a pilot study and is limited by its small sample size. RESULTS: The results of the questionnaires showed significant differences in the group that received mindfulness training compared with the control group, namely, improvements in sleep quality, a reduction in the severity of insomnia, a better quality of life, improved attention levels, and a reduction in menopausal and vasomotor symptoms. Polysomnography results showed no differences between the groups. CONCLUSIONS: Eight weeks mindfulness meditation training improved sleep quality, quality of life, attention levels, and reduced vasomotor symptoms in postmenopausal women with insomnia. PMID- 29787481 TI - Sex hormone levels and risk of primary open-angle glaucoma in postmenopausal women. AB - OBJECTIVE: We evaluated the relation of prediagnostic sex hormone levels in postmenopausal women with primary open-angle glaucoma (POAG) and intraocular pressure (IOP). METHODS: Among postmenopausal participants of the Nurses' Health Study, POAG cases (n = 189; diagnosed 1990-2008) and controls (n = 189) were matched on age, fasting status, and postmenopausal hormone use at blood draw (1989-1990). Plasma concentrations of estrone sulfate, estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate were assessed. The primary outcome was POAG; in secondary analyses, among cases only, we evaluated maximum untreated IOP at diagnosis. Multivariable-adjusted logistic/multiple linear regression models were used to evaluate tertiles (Ts) of biomarker levels and the two outcomes, adjusting for various potential confounders. RESULTS: We observed no significant associations of estrone, estradiol, sex hormone binding globulin, or dehydroepiandrosterone sulfate with POAG risk or with maximum IOP at glaucoma diagnosis among cases. Suggestive significant associations were observed with highest testosterone and POAG risk (T3 vs T1 multivariable-adjusted odds ratio 1.84; 95% confidence interval 1.02, 3.33; P trend 0.10). Similarly, for maximum IOP at diagnosis among cases only (mean 8 years after blood draw), higher testosterone was significantly associated with higher IOP (multivariable-adjusted difference in IOP T3 vs T1 2.17 mm Hg; 95% confidence interval 0.34, 3.99; P trend 0.02). CONCLUSIONS: Overall, plasma sex hormone levels in postmenopausal women were not associated with POAG risk; however, a trend of higher testosterone levels being associated with higher POAG risk and higher IOP at diagnosis was observed and needs confirmation. PMID- 29787484 TI - Post-therapy Functional Magnetic Resonance Imaging in Adults with Symptomatic Convergence Insufficiency. AB - SIGNIFICANCE: Prior studies have demonstrated the effectiveness of vergence accommodative therapy in the treatment of convergence insufficiency (CI). These results show the changes in brain activation following therapy through the use of functional magnetic resonance imaging (fMRI). PURPOSE: The purpose of this study was to investigate changes in brain activation following office-based vergence accommodative therapy versus placebo therapy for CI using the blood oxygenation level-dependent signal from fMRI. METHODS: Adults (n = 7, aged 18 to 30 years) with symptomatic CI were randomized to 12 weeks of vergence-accommodative therapy (n = 4) or placebo therapy (n = 3). Vergence eye movements were performed during baseline and outcome fMRI scans. RESULTS: Before therapy, activation (z score >= 2.3) was observed in the occipital lobe and areas of the brain devoted to attention, with the largest areas of activation found in the occipital lobe. After vergence-accommodative therapy, activation in the occipital lobe decreased in spatial extent but increased in the level of activation in the posterior, inferior portion of the occipital lobe. A new area of activation appeared in the regions of the lingual gyrus, which was not seen after placebo therapy. A significant decrease in activation was also observed in areas of the brain devoted to attention after vergence-accommodative therapy and to a lesser extent after placebo therapy. CONCLUSIONS: Observed activation pre-therapy consistent with top-down processing suggests that convergence requires conscious effort in symptomatic CI. Decreased activation in these areas after vergence-accommodative therapy was associated with improvements in clinical signs such as fusional vergence after vergence-accommodative therapy. The increase in blood oxygen level dependent response in the occipital areas following vergence-accommodative therapy suggests that disparity processing for both depth and vergence may be enhanced following vergence-accommodative therapy. PMID- 29787485 TI - The Effect of Contact Lens Wear on the Cellular Morphology of the Lid Wiper Area. AB - SIGNIFICANCE: This cross-sectional study presented a link between contact lens wear and changes on the cellular morphology characteristics of the lid wiper (LW) epithelium, which was not visible by LW staining. PURPOSE: The aim of this study was to establish if the duration of contact lens (CL) wear affects the cellular morphology of the LW epithelium. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience of CL wear; previous CL wearers; and nonwearers (NWs) as controls. Impression cytology samples were collected from the central upper lid margin (LW area). After fixing, samples were stained with periodic acid-Schiff and haematoxylin for cell morphology analysis and subsequently graded according to the Nelson 0- to 3-point scale. Lid wiper staining was assessed with the aid of lissamine green and graded using the Korb (0- to 3-point) scale. One-way Kruskal Wallis analysis followed by the Dunn multiple-comparisons test was used for statistical comparison. RESULTS: The Nelson grade for LW epithelium morphology was significantly different between groups (P = .003). Abnormal epithelial morphology as defined by grade 2 or 3 was evident in 66.7% of CL wearers with short experience and 76.5% of CL wearers with moderate experience. This was significantly higher than NWs of whom only 21.5% showed greater than grade 1 (P = .02 and .005, respectively). There was no significant difference between NWs and other groups. Lid wiper staining did not significantly differ between groups (P = .50) or correlate with the Nelson grade (Spearman r = 0.02, P = .08). CONCLUSIONS: Metaplasia of the LW epithelium was significantly greater in the early to moderate stages of CL. This supports the view that mechanical irritation is responsible for LW changes in CL wear. Ceasing CL wear seems to lead to recovery. Lid wiper staining did not reflect the underlying morphological changes. PMID- 29787486 TI - A Random Dot Computer Video Game Improves Stereopsis. AB - SIGNIFICANCE: Currently, treatments for amblyopia are occlusion or penalization of the stronger fellow eye. Fewer than 30% of patients improve stereoacuity using these treatments. In order to improve these outcomes, this group proposes a treatment to stimulate the stereoacuity through perceptual learning in a game format for use at home. PURPOSE: The aim of this study was to determine whether perceptual learning with random dot stimuli (RDS) in the form of a computer video game improves stereopsis in patients with a history of amblyopia. METHODS: Thirty two stereo-deficient patients (7 to 14 years old) previously treated for amblyopia participated in a prospective, randomized, double-blind study. Participants followed a perceptual learning program at home using RDS software. In the experimental group, the demand of stereopsis was increased, until reaching the lowest detectable disparity. In the comparison group, the stimulation interval was a constant (840 to 750"). Stereoacuity was evaluated with the Randot Preschool Stereoacuity Test (RPST) and the Wirt Circles. RESULTS: Median compliance was 100% (interquartile range [IQR] = 78.50 to 100). Log10 stereoacuity outcomes were significantly different between groups (RPST, P = .041; Wirt Circles Test, P = .009). Median stereoacuity improvement with RPST was 50% (IQR = 0.00 to 75%) and 0% (IQR = 0.00 to 7.5%), respectively, for experimental and comparison groups (P = .008). Wirt Circles improvement was 46.42% (IQR = 6.25 to 73.75%) and 0% (IQR = 0.00 to 57.50%), respectively, for experimental and comparison groups (P = .089). Stereoacuity improvement was not different between groups when success was considered a 70% gain in RPST (P = .113); it was statistically different when success was considered a gain of two levels on Wirt Circles and stereoacuity 140" or less (P = .023). Stereoacuity remained stable after 6 months when measured with RPST, whereas it worsened in two subjects when measured with Wirt Circles. CONCLUSIONS: Direct stimulation of stereopsis at home using RDS in a game environment improves the stereoacuity in stereo-deficient subjects with a history of amblyopia. PMID- 29787487 TI - Case Report: Hydroxychloroquine Retinopathy. AB - SIGNIFICANCE: Hydroxychloroquine retinopathy causes irreversible central visual loss and can progress despite medication discontinuation. Appropriate dosing and recognition of early disease are important to minimize adverse visual sequelae. In 2016, the American Academy of Ophthalmology updated its 2011 recommendations for dosing, screening, and monitoring of hydroxychloroquine retinopathy. PURPOSE: The aim of this study was to report a case of hydroxychloroquine retinopathy in a patient who developed toxicity on a dose meeting safety thresholds from the 2011 guidelines (i.e., 6.5 mg/kg ideal body weight and cumulative dose <1000 g), but exceeding that from the 2016 revised recommendations (i.e., 5.0 mg/kg real body weight). CASE REPORT: A 61-year-old woman with rheumatoid arthritis treated with 400 mg/kg hydroxychloroquine daily for 6 years (daily dose, 5.72 mg/real body weight or 6.5 mg/kg ideal body weight; cumulative dose, 876 g) experienced progressive central vision loss and a scotoma affecting her reading ability and was referred to the Retina service. Prior yearly examination with only Ishihara color vision and Amsler grid testing was normal. On examination, visual acuity was 20/40 in the right eye and 20/30 in the left eye. A fundus examination showed bilateral bull's-eye maculopathy, a classic finding of hydroxychloroquine retinal toxicity. Fundus autofluorescence showed a parafoveal ring of speckled hypoautofluorescence and an external ring of increased signal. There were characteristic structural changes on spectral domain-optical coherence tomography, including parafoveal loss of the ellipsoid zone and outer nuclear layer. Humphrey visual field testing of the central 10-2 revealed incomplete paracentral annular scotoma. Subsequently, hydroxychloroquine was switched to sulfasalazine. CONCLUSIONS: The 2016 American Academy of Ophthalmology guidelines for hydroxychloroquine retinopathy were revised to reflect new dosing and care guidelines for early detection of retinal toxicity and to minimize the extent of irreversible vision loss. PMID- 29787488 TI - Effects of Scleral-lens Tear Clearance on Corneal Edema and Post-lens Tear Dynamics: A Pilot Study. AB - SIGNIFICANCE: The present study with small-diameter scleral lenses (SLs) revealed that post-lens tear thickness (PoLTT) was significantly associated with post-lens tear mixing, but not with central corneal edema, after short-term SL wear. PURPOSE: The aim of this study was to investigate the influence of SL tear clearance (PoLTT) on central corneal thickness and post-lens tear dynamics during 5-hour lens wear. METHODS: Neophytes with no active ocular disease were fitted bilaterally with SLs (hofocon A; 15.6-mm diameter; ~438-MUm thickness; 97 Dk; 1.44 refractive index) with various initial PoLTT values ranging from 74 to 543 MUm. Central corneal thickness and PoLTT were measured using optical coherence tomography during lens wear. Tear mixing was assessed using fluorogram and "out in" method. RESULTS: The mean central corneal edema after 5-hour lens wear was 1.51% (95% confidence interval, 1.26 to 1.76%; P < .001), reached its peak at 2 hour post-lens insertion (1.65% [95% confidence interval, 1.45 to 1.85%]), and was independent of PoLTT. The fastest fluorescence decay of the post-lens tear film was observed superiorly. The fluorescence decay rate increased from center to periphery in all quadrants except superiorly. An inverse relationship was found between PoLTT and fluorescence decay rate at both 20-minute and 5-hour wear after lens insertion (P < .05). Excluding observations with out-in time exceeding 5 minutes, we found a direct relationship between PoLTT at 20 minutes after lens insertion and out-in time (P = .047). The % change in the PoLTT after 5-hour wear was greater with a thinner initial tear clearance than those with a thicker one (P = .034). CONCLUSIONS: Within our study parameters, a thinner PoLTT under a small-diameter SL was associated with faster PoLTT mixing. However, there was no relationship between PoLTT and central corneal thickness during 5-hour SL wear. PMID- 29787489 TI - Case Report: Optical Coherence Tomography Angiography in Morning Glory Disc Anomaly. AB - SIGNIFICANCE: Morning glory disc anomaly is a congenital abnormality of the optic disc. Optical coherence tomography angiography shows vascular rarefaction of the superficial and deep capillary plexuses and increased vascularity of the radial peripapillary capillary plexus. We hypothesize that this congestion represents a compensatory mechanism to an abnormal vasculogenesis. PURPOSE: The aim of this study was to describe the optic disc vascular alterations occurring at choriocapillaris and retinal vascular plexuses in a patient affected by bilateral morning glory disc anomaly with optical coherence tomography angiography. CASE REPORT: A 24-year-old white man presented for clinical evaluation to our Department of Ophthalmology (San Raffaele Hospital, Milan) complaining of reduced vision in his left eye. Whereas his right eye was unremarkable (20/20), the visual acuity in the left one was limited to 20/30 Snellen equivalent. Funduscopic examination revealed bilateral funnel-shaped optic disc excavation, with a central mass of glial tissue and straight retinal vessels radially emerging from the disc margin, more evident in the left eye; this presentation was considered compatible with bilateral morning glory disc anomaly. Optical coherence tomography angiography of the optic disc disclosed prominent vascular rarefaction of the peripapillary superficial and deep capillary plexuses and choriocapillaris, with an increased vascularity of the radial peripapillary capillary network. CONCLUSIONS: Based on these observations, we hypothesize that the congestion of the radial peripapillary capillary plexus might be a compensatory mechanism to the abnormal vasculogenesis occurring in the optic disc of patients affected by morning glory disc anomaly. PMID- 29787490 TI - Clinical Performance of a New Bitangential Mini-scleral Lens. AB - SIGNIFICANCE: New bitangential mini-scleral lens designs provide a highly precise fit, follow the scleral shape, are comfortable to wear, and can correct residual astigmatism. This new scleral lens design complements the arsenal of medical contact lenses available to eye care practitioners. PURPOSE: The aim of this study was to evaluate the subjective and objective performance of a new mini scleral lens design with a bitangential periphery. METHODS: In this observational study, data were collected for up to 15 months (median, 84 days; interquartile range, 76 days) from the left eyes of 133 patients fitted with this newly designed lens. Data were recorded during regular visits at Visser Contact Lens Practice's scleral lens clinics: diagnosis, clinical indication for scleral lenses, previous contact lens type, subjective performance, horizontal visible iris diameter, corrected distance visual acuity, and scleral lens fitting characteristics. RESULTS: The most common indication was keratoconus (45%), followed by irregular astigmatism (22%), keratoplasty (16.5%), ocular surface disease (13.5%), and other forms of irregular astigmatism (3%). The majority of patients (79%) scored comfort as either a 4 or 5 (out of 5), and 82% wore their lenses 12 hours or longer a day. Most lenses (81%) had a diameter of 16 mm (median, 16 mm; range, 15.5 to 17 mm) and were composed of Boston XO2 (46%), Menicon Z (44%), Boston XO (9%), or Boston Equalens II (1%). The median corrected distance visual acuity was 0.022 logarithm of the minimal angle of resolution (interquartile range, 0.155). The fitting characteristics revealed optimal values for centration and movement in 91% and 83%, respectively. Finally, the median stabilization axis was 50 degrees. CONCLUSIONS: New mini-scleral lenses with bitangential peripheral geometry yield satisfactory clinical results and good subjective performance and are therefore an effective option for managing patients who have irregular astigmatism or other corneal pathology. PMID- 29787491 TI - Detecting Cheating when Testing Vision: Variability in Acuity Measures Reveals Misrepresentation. AB - SIGNIFICANCE: In certain scenarios, it is advantageous to misrepresent one's ability and "cheat" on vision tests. Our findings suggest that increased variability when testing visual acuity holds promise as a novel means to help detect this cheating and may generalize to other subjective tests of visual function. PURPOSE: People who cheat on vision tests generally do so to make their vision appear better than it actually is (e.g., for occupational or driving purposes). However, there are particular settings in which it is advantageous for their vision to appear to be worse than is the case (e.g., to qualify for benefits available to people with low vision). Therefore, a method to help detect cheating in these scenarios is desirable. The aim of this study was to investigate whether the intentional underrepresentation of vision could be detected when testing visual acuity. METHODS: We tested the visual acuity of 13 participants with simulated vision impairment using the Berkeley Rudimentary Vision Test. Participants were tested in an honest condition when providing their best effort and in a cheating condition when attempting to make their visual acuity appear to be markedly worse. We also tested visual acuity of 17 participants with a wide range of vision impairments. RESULTS: Participants were successfully able to "cheat" on the tests; however, their responses were significantly more variable when cheating (P < .001). Although the variability in visual acuity was larger in individuals with actual vision impairment compared with those providing honest answers with simulated impairment (P < .01), their responses remained significantly less variable than those for individuals in the cheating condition (P = .01). CONCLUSIONS: The variability in the estimations of vision provides a promising novel means of detecting the intentional underrepresentation of vision and could help to minimize the chance of successfully cheating on tests of vision. PMID- 29787492 TI - Dot Motion Perception in Young Adult Emmetropes and Myopes. AB - SIGNIFICANCE: Central motion perception, as assessed by minimum displacement detection, was reduced in highly myopic eyes. Peripheral motion detection may be influenced by myopia, particularly in the inferior-nasal retina. PURPOSE: Motion discrimination is a complex visual task processed mainly via the magnocellular pathway. We investigated whether it is affected in myopia. METHODS: Ninety young adults aged 18 to 28 years participated: 30 emmetropes (spherical equivalent refractions +1.00 to -0.50 diopters [D]), 30 low myopes -1.00 to -4.75 D) and 30 higher myopes (<-5 D). Random dot patterns were used to measure motion perception thresholds for minimum displacement (Dmin), maximum displacement (Dmax), and motion coherence tasks. Each task was performed centrally and at four oblique peripheral visual field locations (at 3.65 and 12 degrees for Dmin and Dmax tasks, respectively). Macular retinal thickness was measured with optical coherence tomography. RESULTS: The central Dmin task was correlated significantly with refraction (r = -0.303, P = .004) and axial length (r = +0.224, P = .04), and the superior-temporal field Dmin task was correlated significantly with axial length (r = 0.230, P = .04). Higher myopes had poorer performance than emmetropes by 25% (higher values). For the Dmin peripheral task and for Dmax and coherence tasks at both central and peripheral locations, there were no significant correlations with refraction or axial length. At three of four positions, the peripheral Dmin task was correlated significantly with thickness in the corresponding retinal region: superior-temporal Dmin (Pearson r = -0.357, P < .001), inferior-nasal Dmin (r = -0.237, P = .03) and inferior-temporal Dmin (r = 0.233, P = .03). CONCLUSIONS: Central motion perception, as assessed by minimum displacement detection, was reduced by 25% in highly myopic eyes. Peripheral motion detection may be influenced by myopia, particularly in the inferior-nasal retina. Retinal stretching due to axial elongation may be linked to reduced performance in higher myopes. PMID- 29787493 TI - Computed Diffusion Weighted Imaging of the Liver Using Extrapolation Technique in Patients Who Underwent Liver Transplantation With Hepatocellular Carcinomas: Initial Experience and Feasibility Study. AB - OBJECTIVE: This study aimed to evaluate the feasibility and image quality of computed diffusion weighted imaging (DWI) of the liver in patients with hepatocellular carcinoma (HCC). METHODS: Twenty-four patients who underwent liver transplantation with HCC were enrolled. Computed DWI was synthesized for b-values of 800 (cDWI800) and 1200 s/mm (cDWI1200) using directly acquired DWI with b values of 0, 50, and 500 s/mm. Signal intensity of HCC, background liver, and contrast-to-noise ratio were evaluated for directly acquired DWI of 800 s/mm (dDWI800), cDWI800, and cDWI1200. Two radiologists evaluated the image quality for contrast between HCC and liver, suppression of background signal and T2 shine through, and overall image quality. RESULTS: cDWI1200 showed the lowest contrast to-noise ratio. Qualitative scores for background suppression and decreased T2 shine-through were highest for cDWI1200. However, contrast between HCC and background liver was worst in cDWI1200. CONCLUSIONS: In computed DWI of high b values, contrast between HCC and background liver was very low. PMID- 29787494 TI - "Barbell Sign": A Diagnostic Imaging Finding in Progressive Multifocal Leukoencephalopathy. AB - The recently proposed diagnostic algorithm for progressive multifocal leukoencephalopathy underscores the importance of imaging and emphasizes the role of the radiologist in the diagnostic workup. We describe a case series of patients with visual symptoms and a typical pattern of brain involvement in definite progressive multifocal leukoencephalopathy, for which we have coined the term barbell sign. PMID- 29787495 TI - Differentiating Neuromyelitis Optica-Related and Multiple Sclerosis-Related Acute Optic Neuritis Using Conventional Magnetic Resonance Imaging Combined With Readout-Segmented Echo-Planar Diffusion-Weighted Imaging. AB - PURPOSE: In clinical practice, acute optic neuritis (ON) associated with the development of neuromyelitis optica (NMO) after the first attack is often indistinguishable from that associated with multiple sclerosis (MS). We aimed to determine the optimal combination of features derived from conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging using readout-segmented echo-planar imaging (RESOLVE-DWI) for the differentiation of these conditions. MATERIALS AND METHODS: Orbital conventional MRI and RESOLVE-DWI were performed using a 3.0-T scanner on 54 patients with acute ON (26 NMO-related and 28 MS related). The features detected by conventional MRI (including laterality, the enhancement pattern, and the extent and position of involvement) and the apparent diffusion coefficient (ADC) measurements were retrospectively compared between the NMO-related and MS-related groups. A multivariate logistic regression analysis was used to identify the most significant variables, and receiver operating characteristic curve analyses were performed to determine the ability of a combined diagnostic model based on the qualitative and quantitative characteristics identified in this study to differentiate the 2 conditions. RESULTS: The multivariate logistic regression analyses indicated that the presence of chiasm involvement and lower ADC values were significantly associated with NMO-related acute ON compared with MS-related acute ON (P = 0.037 and 0.008, respectively). The diagnostic criterion of chiasm involvement or "ADC < 791 * 10 mm/s and chiasm involvement" had the highest specificity (96.9%), and "ADC < 791 * 10 mm/s or chiasm involvement" showed the optimal sensitivity (77.8%) for differentiating NMO-related from MS-related acute ON. CONCLUSIONS: Conventional MRI RESOLVE-DWI is helpful for differentiating NMO-related acute ON from MS related acute ON. The combination of the ADC value chiasm involvement appears to be effective for discriminating these 2 types of acute ON. PMID- 29787496 TI - Quantitative Comparison of Virtual Monochromatic Images of Dual Energy Computed Tomography Systems: Beam Hardening Artifact Correction and Variance in Computed Tomography Numbers: A Phantom Study. AB - OBJECTIVE: The aim of this study was to quantitatively compare the reduction in beam hardening artifact (BHA) and variance in computed tomography (CT) numbers of virtual monochromatic energy (VME) images obtained with 3 dual-energy computed tomography (DECT) systems at a given radiation dose. METHODS: Five different iodine concentrations were scanned using dual-energy and single-energy (120 kVp) modes. The BHA and CT number variance were evaluated. RESULTS: For higher iodine concentrations, 40 and 80 mgI/mL, BHA on VME imaging was significantly decreased when the energy was higher than 50 keV (P = 0.003) and 60 keV (P < 0.001) for GE, higher than 80 keV (P < 0.001) and 70 keV (P = 0.002) for Siemens, and higher than 40 keV (P < 0.001) and 60 keV (P < 0.001) for Toshiba, compared with single energy CT imaging. CONCLUSIONS: Virtual monochromatic energy imaging can decrease BHA and improve CT number accuracy in different dual-energy computed tomography systems, depending on energy levels and iodine concentrations. PMID- 29787497 TI - Magnetic Resonance Imaging Features of Breast Encapsulated Papillary Carcinoma. AB - OBJECTIVE: This study aimed to describe the magnetic resonance imaging (MRI) features of pure breast encapsulated papillary carcinoma (EPC). MATERIALS AND METHODS: Ten patients with histopathologically confirmed breast pure EPC were reviewed. Two radiologists evaluated lesion MRI characteristics. RESULTS: The EPC presented oval or round mass with circumscribed margin on MRI. In addition, 4 cases exhibited a cystic-solid mixed mass with mural nodules, and 4 cases exhibited a liquid level that indicated the possibility of hemorrhage. CONCLUSIONS: A well-defined cystic-solid mixed mass with mural nodules, or a circumscribed mass exhibiting the possibility of hemorrhage, may suggest the diagnosis of EPC. PMID- 29787498 TI - The Value of Modified Renal Rim Grade in Predicting Acute Kidney Injury Following Severe Acute Pancreatitis. AB - OBJECTIVE: To retrospectively determine the value of modified renal rim grade (MRRG) in predicting acute kidney injury (AKI) in the early phase of severe acute pancreatitis (SAP). METHODS: This institutional review board-approved retrospective study included patients with SAP who underwent abdominal contrast enhanced computed tomography (CT) within 48 hours after disease onset. Modified renal rim grade, renal rim grade, CT severity index, modified CT severity index, extrapancreatic inflammation on CT scores, and posterior pararenal (PPR) space involvement were assessed. Clinical data, including bedside index of severity in acute pancreatitis and New Japanese Severity Scoring system scores, were collected. Primary end points were AKI and mortality. Scores were evaluated by receiver operating characteristic curve analysis. Correlational analyses between MRRG scores and the other scores were performed with Spearman analysis. RESULT: One hundred five consecutive patients were enrolled in our study. The areas under the curve (AUCs) of MRRG in predicting AKI (0.90) and mortality (0.83) were comparable to extrapancreatic inflammation on CT (0.89 and 0.85, P > 0.05) and were higher than those of the other CT scores (P < 0.05). Modified renal rim grade score of greater than 4 yielded sensitivities and specificities of 81% and 89% for predicting AKI and 88% and 66% for mortality. Modified renal rim grade correlated moderately with bedside index of severity in acute pancreatitis (Spearman r = 0.47) and New Japanese Severity Scoring system (r = 0.43) scores. Besides, the prevalence of PPR space involvement in nonrecovery AKI patients was higher than that in recovery patients (94% vs 36%, P < 0.05). CONCLUSIONS: Modified renal rim grade is well correlated with the occurrence of AKI and mortality in SAP. The PPR space involvement is a promising prognostic factor for nonrecovery of AKI in SAP patients. PMID- 29787499 TI - Acute Appendicitis Involving a De Garengeot Hernia. AB - We present a case of appendicitis within a De Garengeot hernia. The patient presented to the emergency department with 4 days of worsening abdominal pain. Computed tomography examination revealed an inflamed appendix within a femoral hernia. The patient underwent appendectomy and repair of the femoral defect. Pathological examination was consistent with acute appendicitis. De Garengeot hernia is a rare phenomenon, with less than 5% of femoral hernias containing the appendix and 0.08% to 0.13% containing an incarcerated acute appendicitis. PMID- 29787500 TI - Evaluation of the Communication Between Arachnoid Cysts and Neighboring Cerebrospinal Fluid Spaces by T2W 3D-SPACE With Variant Flip-Angle Technique at 3 T. AB - PURPOSE: Phase-contrast cine magnetic resonance imaging (PC-MRI) is a widely used technique for determination of possible communication of arachnoid cysts (ACs). Three-dimensional (3D) sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) technique is a relatively new method for 3D isotropic scanning of the entire cranium within a short time. In this research, the usage of the 3D-SPACE technique in differentiation of communicating or noncommunicating type ACs was evaluated. MATERIALS AND METHODS: Thirty-five ACs in 34 patients were retrospectively examined. The 3D-SPACE, PC MRI, and contrast material-enhanced cisternography (if present) images of the patients were analyzed. Each cyst was described according to cyst size/location, third ventricle diameter, Evans index, and presence of hydrocephalus. Communication was defined as absent (score 0), suspected (score 1), or present (score 2) on each sequence. Results of PC-MRI or cisternography (if available) examinations were used as criterion standard techniques to categorize all cysts as communicating or noncommunicating type. The results of 3D-SPACE were compared with criterion standard techniques. The comparisons between groups were performed using Mann-Whitney and Fisher exact tests. RESULTS: For demonstration of communication status of the cysts, criterion standard test results and 3D-SPACE findings were almost in perfect harmony (kappa[95% confidence interval: 0.94]; P < 0.001). When evaluating the communicative properties, 3D-SPACE findings correlated with other final results at a rate of 97%. There is a positive correlation with third ventricular diameters and Evans index for all patients (r = 0.77, P < 0.001). For other analyzed variables, there is no significant difference or correlation between the groups. CONCLUSIONS: The 3D-SPACE technique is an easy, useful, and noninvasive alternative for the evaluation of morphology, topographical relationships, and communication status of ACs. PMID- 29787501 TI - An Apparent Diffusion Coefficient Histogram Method Versus a Traditional 2 Dimensional Measurement Method for Identifying Non-Puerperal Mastitis From Breast Cancer at 3.0 T. AB - PURPOSE: This study aimed to investigate the utility of a volumetric apparent diffusion coefficient (ADC) histogram method for distinguishing non-puerperal mastitis (NPM) from breast cancer (BC) and to compare this method with a traditional 2-dimensional measurement method. MATERIALS AND METHODS: Pretreatment diffusion-weighted imaging data at 3.0 T were obtained for 80 patients (NPM, n = 27; BC, n = 53) and were retrospectively assessed. Two readers measured ADC values according to 2 distinct region-of-interest (ROI) protocols. The first protocol included the generation of ADC histograms for each lesion, and various parameters were examined. In the second protocol, 3 freehand (TF) ROIs for local lesions were generated to obtain a mean ADC value (defined as ADC-ROITF). All of the ADC values were compared by an independent-samples t test or the Mann-Whitney U test. Receiver operating characteristic curves and a leave-one-out cross validation method were also used to determine diagnostic deficiencies of the significant parameters. RESULTS: The ADC values for NPM were characterized by significantly higher mean, 5th to 95th percentiles, and maximum and mode ADCs compared with the corresponding ADCs for BC (all P < 0.05). However, the minimum, skewness, and kurtosis ADC values, as well as ADC-ROITF, did not significantly differ between the NPM and BC cases. CONCLUSIONS: Thus, the generation of volumetric ADC histograms seems to be a superior method to the traditional 2 dimensional method that was examined, and it also seems to represent a promising image analysis method for distinguishing NPM from BC. PMID- 29787502 TI - Evaluation of Stomach Neoplasms With 3-Dimensional Computed Tomography: Focus on the Potential Role of Cinematic Rendering. AB - Evaluation of stomach neoplasms by traditional 3-dimensional (3D) computed tomography methods such as volume rendering and maximum-intensity projection plays an important role in lesion detection and characterization, preoperative planning, staging, and follow-up. Recently, a new 3D visualization method has become available known as cinematic rendering (CR). This novel technique makes use of a complex global lighting model to impart photorealistic levels of detail to 3D images. Although this new technique has yet to be systematically studied for the evaluation of stomach neoplasms, its intrinsic ability to create realistic shadowing effects to enhance understanding of the 3D relative locations of anatomic structures and to enhance detail and texture may prove valuable for a variety of applications. In this article, we demonstrate the CR appearance of multiple different gastric neoplasms, describe potential advantages of CR, and suggest future research directions. PMID- 29787503 TI - Deaths of Despair and Building a National Resilience Strategy. PMID- 29787504 TI - The North American Opioid Experience and the Role of Community Pharmacy. PMID- 29787505 TI - Preventing Leader Derailment-A Strategic Imperative for Public Health Agencies. PMID- 29787506 TI - Lessons in Infection Control: The Role of Local Health Departments in Prevention, Preparedness, and Response. PMID- 29787507 TI - At What Distance Can One Assess Diversity? PMID- 29787508 TI - Impact of a Required Service-Learning Curriculum on Preclinical Students. AB - PURPOSE: The impact of brief service-learning curricula on physician assistant (PA) students is not well reported. This study explores student learning immediately and then one to 2 years after a preclinical service-learning experience through written reflections and a survey. METHODS: The 16-hour curriculum within a behavioral science course involved community immersion and engagement with underserved clients. Reflections written by students from 3 consecutive classes were coded for major themes, and theme frequency was assessed. We then administered a survey to explore the curricular impact after students completed their clinical clerkships. RESULTS: All students (132/132) completed the required curriculum. We identified 4 major themes from 132 reflections. The themes were (most to least frequent) self-discovery (54/132), patient focus (30/132), community resources (28/132), and patient-provider relationship (20/132). The primary attitude change (self-discovery) was student awareness of their own biases and recognition of the need for cultural humility when caring for underserved clients. In the postcurriculum survey (response 69/95), students recalled community resources as the most important learning, followed by self-discovery. Students viewed the curriculum positively and noted that the exposure increased their comfort with caring for underserved patients in their clerkships. CONCLUSIONS: Immersion in a community-based service-learning experience with underserved clients is associated with increased self-awareness and intent to change behavior. Students perceive the experience as important for future clerkships. Preclinical service-learning curricula prepare students to care for underserved patients. PMID- 29787509 TI - Use of Moulage to Evaluate Student Assessment of Skin in an Objective Structured Clinical Examination. AB - PURPOSE: This study investigated the physician assistant (PA) student evaluation of skin and the use of moulage in an objective structured clinical examination (OSCE). METHODS: Clinical-year PA students participated in an OSCE, taking a history, completing a physical examination, and writing a focused clinical note. The standardized patient's history simulated a primary diagnosis of right-sided carpal tunnel syndrome and an incidental skin lesion consistent with melanoma, only if the student made an inquiry in this replication study. Faculty members' assessments of students' physical examinations were standardized using an agreed upon rubric. Students completed an anonymous survey on the OSCE experience immediately following the activity. RESULTS: All students identified the primary diagnosis of carpal tunnel. Sixty-three percent of students verbalized examination of the skin; however, only 38% identified an atypical skin lesion in their clinical note documentation. Of those, only 33% of students referred the patient for biopsy. Most students believed that the use of moulage increased the realism of the standardized patient encounter. Sixty percent of students reported that they noticed a skin lesion but did not believe that it was part of the simulated experience. CONCLUSIONS: Moulage increased the realism of the OSCE. This study found that the ability of a student to verbalize the evaluation of a particular body system did not necessarily mean that they adequately or correctly assessed that system upon physical examination. Implementation of an OSCE and use of moulage provided an opportunity to explicitly assess student performance related to evaluation and assessment of skin. It provided a mechanism for meaningful, formative feedback of students' performance. PMID- 29787510 TI - Metacognition, Formative Assessment, and Student Perspective: Learning About Metacognition Through In-Class Comparison of Response Systems. AB - PURPOSE: Educators influence learning context through, among other things, triadic reciprocal causation-a behavioral model used in social cognitive theory. Eliciting responses from learners during instruction may contribute to learning by engaging their metacognition. In this study, metacognition was examined based on learners' experience with 2 different polling methods: student response systems (SRS), commonly known as "clickers," and a low-technology response system (LTRS), where students raise labeled signs, each with a different response. Scale item results are reported. METHODS: Scales measuring the influence of metacognition from polling methods were administered, following treatment (SRS) and comparison method (LTRS), to first-year physician assistant (PA) students (n = 54). Statistical tests of significance and effect size for each item were compared. RESULTS: Performance outcomes suggest that the SRS enhances learning experiences more than low-technology polling. Self-reported surveys indicate that self-monitoring, note-taking, and understanding during lectures are significantly improved with the use of clickers. Peer and social comparison items did not demonstrate significance collectively, but survey results indicate that candidates compared themselves to their peers significantly more with the LTRS than with the SRS. CONCLUSION: Findings support the practice of using an electronic SRS to poll PA students and enhance learning. PMID- 29787511 TI - The Mechanism of Heartbreak. PMID- 29787512 TI - Browning of Human Subcutaneous Adipose Tissue after Its Transplantation in Nude Mice. AB - BACKGROUND: The clinical unpredictability of autologous fat grafting originates partially from the unique characteristics of adipose tissue. Evidence of adipose remodeling toward browning (developing of brown-like adipocytes in white adipose tissue) in response to trauma has been emerging. With regard to fat grafting surgery by which adipose tissue depots are directly and ubiquitously traumatized, whether it affects adipose phenotype change toward browning has not been previously reported. METHODS: Human subcutaneous adipose tissues were harvested from the abdominal region of female patients by means of liposuction and were then injected into the dorsal flanks of athymic nude mice. After 12 weeks, fat grafts were harvested and subjected to histologic analysis. RESULTS: Hematoxylin and eosin staining showed the appearance of small multilocular adipocytes in the peripheral region of the grafts. These adipocytes exhibited higher staining for uncoupling protein 1 (a fat browning-specific marker), mitochondrial protein, and CD31 compared with the central ones, indicating the presence of brown-like adipocytes (i.e., beige adipocytes) in this area. Furthermore, immunofluorescence staining demonstrated that these beige adipocytes might be derived from de novo adipogenesis from progenitors of graft origin. CONCLUSION: Results of this study suggest that browning of subcutaneous white adipose tissue participates in adaptive tissue remodeling following grafting and contributes to adipose tissue repair. PMID- 29787513 TI - Real-Time Ultrasound-Assisted Gluteal Fat Grafting. AB - BACKGROUND: The number of gluteal fat augmentation procedures has increased recently and so has the number of complications. Because of the increased risk of morbidity and mortality when fat is injected intramuscularly, not knowing where fat is injected is concerning. We sought to identify the planes in which fat is injected during the procedure. METHODS: We selected 15 consecutive female patients who desired gluteal fat augmentation. All patients had epidural anesthesia and the gluteal region was infiltrated with a vasoconstrictive solution. With the patient in prone position, an ultrasound probe placed on the buttocks was used to identify the fascial layers. While decanted fat was being injected with a blunt cannula, the images were projected wirelessly to a screen, so that the surgeon and assistant could follow the planes in which the cannula was being introduced and the fat injected. RESULTS: The mean volume of harvested fat was 3533 ml and the mean volume of fat injected per gluteal region was 528 ml. The evaluation of the depth and location of the cannula was performed in real time with the ultrasound, accurately and reliably identifying the planes of fat injection. All injections were subcutaneous. The downsides of this technique were the purchase cost of the ultrasound device, increased surgical time, the need for an assistant to follow the cannula and the probe constantly, and the learning curve. CONCLUSION: Real-time ultrasound-assisted gluteal fat grafting is reliable and may avoid injuring the deep vessels, further decreasing the risks of major complications. PMID- 29787514 TI - Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue. AB - BACKGROUND: Clinical sequelae of irradiation result in tissue devitalization (e.g., ischemia, fibrosis, and atrophy) where wound healing capacity is impaired. Fat-derived products may work to treat such pathology. METHODS: Nonlethal irradiation at various doses (5, 10, and 15 Gy) and frequencies (one to three times on sequential days) was delivered to dorsal skin of nude mice, and subsequent gross and microscopic changes were evaluated for up to 4 weeks. Cutaneous punch wounds were then created to compare wound healing in irradiated and nonirradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells, centrifuged fat tissue, or micronized cellular adipose matrix, and the therapeutic impact was monitored for up to 15 days. RESULTS: Nude mice given total doses greater than 15 Gy spontaneously developed skin ulcers, and radiation damage was dose-dependent; however, a fractionated irradiation protocol was able to reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5 to 15 Gy) impairment of wound healing was also evident. At the highest dosage (15 Gy three times), open wounds persisted on day 15. However, wounds injected with cultured adipose-derived stem cells were nearly healed on day 12, and those treated with injection of centrifuged fat or micronized tissue healed faster than untreated controls (p < 0.05). There was no significant differences between treated groups. CONCLUSIONS: Tissue devitalization by irradiation was dose-dependent, although fractionated protocols helped to reduce it. Adipose-derived stem cells and other fat-derived products harboring adipose-derived stem cells successfully revitalized irradiated tissues and accelerated wound healing. PMID- 29787515 TI - The Evolving Role of Blending of the Lid-Cheek Junction in Lower Blepharoplasty. AB - BACKGROUND: Lower blepharoplasty has evolved from traditional lower blepharoplasty involving skin-muscle flaps and fat resection to newer concepts that emphasize blending the lid-cheek junction. It is the objective of this review to evaluate these new concepts for their efficacy in blending the lid cheek junction. METHODS: A comprehensive review of literature was performed using PubMed/MEDLINE to identify studies evaluating fat conservation, fat augmentation, fat repositioning, orbicularis retaining ligament (ORL) release, septal reset, and use of fillers in deep cheek fat compartments to obtain aesthetically pleasing lid-cheek junction. RESULTS: A total of 22 studies meeting inclusion criteria and evaluating fat conservation, fat augmentation, fat repositioning, ORL release, septal reset, and use of fillers in deep cheek fat compartments are analyzed and discussed. CONCLUSIONS: This review provides the current evidence for various strategies that can be used alone or combined to obtain youthful lid cheek junction. It provides the current evidence-based scientific rationale for optimal management of the lower eyelid cheek area for facial rejuvenation. PMID- 29787516 TI - Microanatomy of Sensory Nerves in the Upper Eyelid: A Cadaveric Anatomical Study. AB - BACKGROUND: Plastic surgery requires detailed knowledge of upper eyelid anatomy, but few authors have sufficiently described the specifics of upper eyelid nerve anatomy. This study aimed to provide a thorough description of sensory nerve anatomy in the upper eyelid and to propose considerations for upper eyelid surgery. METHODS: Sixteen orbits were dissected from 16 fixed, adult human cadavers. Microscopically, the authors identified the main trunks of the infratrochlear, supratrochlear, and supraorbital nerves and all branches that projected toward the upper eyelid. The number, size, and distribution of nerve branches were recorded. RESULTS: The branches of the infratrochlear, supratrochlear, and supraorbital nerves covered a wide range in the upper eyelid. The mean numbers of branches per nerve were 1.6 +/- 1.2, 3.2 +/- 1.5, and 2.6 +/- 1.4, respectively. The branches of the infratrochlear nerve were distributed throughout the medial area of the upper eyelid. Those of the supratrochlear nerve were distributed throughout the medial and central areas, and the palpebral branches of the supraorbital nerve were distributed throughout the central and lateral areas of the upper eyelid. The lateral branches of the supraorbital nerve and the cutaneous branches of the lacrimal nerve were distributed in the lateral region of the orbit. CONCLUSIONS: The authors show that upper eyelid sensation is transmitted mainly by the supratrochlear and supraorbital nerves, and the authors provide a map of the distribution of upper eyelid sensory nerves. This precise anatomical knowledge about upper eyelid sensory nerves will facilitate pain control and help minimize nerve injuries during surgery. PMID- 29787518 TI - Hepatitis B and C: Report of the FISPGHAN Working Group: Erratum. PMID- 29787517 TI - Applying standardized uptake values in gallium-67-citrate single-photon emission computed tomography/computed tomography studies and their correlation with blood test results in representative organs. AB - OBJECTIVES: Recently, semiquantitative analysis using standardized uptake value (SUV) has been introduced in bone single-photon emission computed tomography/computed tomography (SPECT/CT). Our purposes were to apply SUV-based semiquantitative analytic method for gallium-67 (Ga)-citrate SPECT/CT and to evaluate correlation between SUV of physiological uptake and blood test results in representative organs. METHODS: The accuracy of semiquantitative method was validated using an National Electrical Manufacturers Association body phantom study (radioactivity ratio of sphere : background=4 : 1). Thereafter, 59 patients (34 male and 25 female; mean age, 66.9 years) who had undergone Ga-citrate SPECT/CT were retrospectively enrolled in the study. A mean SUV of physiological uptake was calculated for the following organs: the lungs, right atrium, liver, kidneys, spleen, gluteal muscles, and bone marrow. The correlation between physiological uptakes and blood test results was evaluated using Pearson's correlation coefficient. RESULTS: The phantom study revealed only 1% error between theoretical and actual SUVs in the background, suggesting the sufficient accuracy of scatter and attenuation corrections. However, a partial volume effect could not be overlooked, particularly in small spheres with a diameter of less than 28 mm. The highest mean SUV was observed in the liver (range: 0.44-4.64), followed by bone marrow (range: 0.33-3.60), spleen (range: 0.52-2.12), and kidneys (range: 0.42-1.45). There was no significant correlation between hepatic uptake and liver function, renal uptake and renal function, or bone marrow uptake and blood cell count (P>0.05). CONCLUSION: The physiological uptake in Ga-citrate SPECT/CT can be represented as SUVs, which are not significantly correlated with corresponding blood test results. PMID- 29787520 TI - Early TLR4 Blockade Attenuates Sterile Inflammation-mediated Stress in Islets During Isolation and Promotes Successful Transplant Outcomes. AB - BACKGROUND: During the isolation process, pancreatic islets are exposed to an environment of sterile inflammation resulting in an upregulated inflammatory state before transplantation. Toll-like receptor 4 (TLR4) has been identified as a major mediator of sterile inflammation. Therefore, we sought to determine whether early TLR4 blockade would be effective in reducing the inflammatory burden in islets pretransplant. METHODS: Islets from C57BL/6 mice were treated with a TLR4 antagonist during the pancreatic ductal perfusion and digestion steps of the isolation process. Islets were then analyzed for inflammation by RT-PCR and Western blot, and for viability and function in vitro. A syngeneic transplant model using a marginal mass of islets transplanted intraportally into mice with streptozotocin-induced diabetes was used to study transplant outcomes after early TLR4 blockade. RESULTS: Diabetic mice receiving 150 islets treated with early TLR4 blockade achieved euglycemia at a higher rate than mice receiving untreated islets (75% vs 29%; P < 0.05) and had improved long-term function (P < 0.05). Serum markers for islet damage and inflammation were significantly reduced posttransplant (P < 0.05). Both the expression of key inflammatory genes and the activation of mitogen-activated protein kinases were reduced by early TLR4 blockade. Islet viability was improved (P < 0.05) while preserving islet insulin secretory capacity postisolation. CONCLUSIONS: Early TLR4 blockade protects islets from sterile inflammation-mediated stress sustained during isolation and promotes positive transplant outcomes. Our findings support the use of early TLR4 blockade during clinical islet isolation procedures to reduce pretransplant inflammation and improve transplant outcomes. PMID- 29787519 TI - Population Health, Ethnicity, and Rate of Living Donor Kidney Transplantation. AB - BACKGROUND: Living donor kidney transplantation has declined in the United States since 2004, but the relationship between population characteristics and rate of living donation is unknown. The goal of our study was to use data on general population health and socioeconomic status to investigate the association with living donation. METHODS: This cross-sectional, ecological study used population health and socioeconomic status data from the CDC Behavioral Risk Factor Surveillance System to investigate the association with living donation. Transplant centers performing 10 or greater kidney transplants reported to the Scientific Registry of Transplant Recipients in 2015 were included. Center rate of living donation was defined as the proportion of all kidney transplants performed at a center that were from living donors. RESULTS: In a linear mixed effects model, a composite index of health and socioeconomic status factors was negatively associated with living donation, with a rate of living donation that was on average 7.3 percentage points lower among centers in areas with more comorbid disease and poorer socioeconomic status (95% confidence interval, -12.2 to -2.3, P = 0.004). Transplant centers in areas with higher prevalence of minorities had a rate of living donation that was 7.1 percentage points lower than centers with fewer minorities (95% confidence interval, -11.8 to -2.3, P = 0.004). CONCLUSIONS: Center-level variation in living donation was associated with population characteristics and minority prevalence. Further examination of these factors in the context of patient and center-level barriers to living donation is warranted. PMID- 29787521 TI - Survival and Metabolic Function of Syngeneic Mouse Islet Grafts Transplanted Into the Hepatic Sinus Tract. AB - BACKGROUND: Islet grafts are transplanted into the liver via a portal vein in 90% of the clinical islet transplantations. However, the portal vein is far from being the ideal infusion site due to its unique drawbacks. These issues necessitated the exploration of an alternatively optimized site for clinical islet transplantation. With the widespread clinical application of percutaneous transhepatic puncture technique, we envisioned the possibility of islet transplantation into the hepatic sinus tract (HST). METHODS: The HST was created by temporarily placing a medically approved material into the hepatic parenchyma of C57BL/6 mice. The syngeneic islets were transplanted into the HST, after which, the nonfasting blood glucose, intraperitoneal glucose tolerance, and morphology were evaluated. RESULTS: A collagen-lined HST was formed by the 28-day implantation of a cylindrical nylon rod. Transplantation of ~300 syngeneic islets into the HST routinely reversed the hyperglycemia of the recipient mice and maintained normoglycemia for longer than 100 days until the graft was removed. The islet grafts within the HST stained positively for insulin, glucagon, and abundant microvessels and achieved comparable results to the islet grafts under the kidney capsule with respect to glycemic control and glucose tolerance. CONCLUSIONS: These results suggested that an HST can be constructed for islet transplantation by temporarily placing a nylon material in the liver parenchyma. The HST is a promising site for clinical islet transplantation, thereby providing a satisfactory environment for the survival and metabolic function of islet grafts. PMID- 29787523 TI - Secondhand Hypertrophy: A Rare Case of Genetically Based Pathology Developing Within a Transplanted Heart. PMID- 29787522 TI - Belatacept in Solid Organ Transplant: Review of Current Literature Across Transplant Types. AB - Calcineurin inhibitors (CNIs) have been the backbone immunosuppressant for solid organ transplant recipients for decades. Long-term use of CNIs unfortunately is associated with multiple toxicities, with the biggest concern being CNI-induced nephrotoxicity. Belatacept is a novel agent approved for maintenance immunosuppression in renal transplant recipients. In the kidney transplant literature, it has shown promise as being an alternative agent by preserving renal function and having a minimal adverse effect profile. There are emerging studies of its use in other organ groups, particularly liver transplantation, as well as using with other alternative immunosuppressive strategies. The purpose of this review is to analyze the current literature of belatacept use in solid organ transplantation and discuss its use in current practice. PMID- 29787525 TI - Lithium batteries: A technological advance with unintended injury consequences. AB - Lithium-ion (Li-ion) batteries have been powering portable electronic equipment since the mid-1990s. Today, they are ubiquitous in portable electronics, with more than four billion manufactured each year. However, Li-ion batteries are also associated with a spectrum of injuries related to the type of device as well as the person using the device. These injuries range from cutaneous injuries due to flame burns and explosions to corrosion injuries from ingestion. This article describes how the composition of Li-ion batteries can cause injury, the types and extent of Li-ion battery-related injuries, and suggests strategies for prevention. PMID- 29787526 TI - The effect of verified pediatric trauma centers, state laws, and crash characteristics on time trends in adolescent motor vehicle fatalities, 1999-2015. AB - BACKGROUND: Motor vehicle crashes are a leading cause of adolescent death from trauma. A recent study found American College of Surgeons-verified pediatric trauma centers (vPTC) were inversely correlated with pediatric mortality, but the analysis was limited to a single year. This study assesses the contribution of vPTCs, crash characteristics, and state driver laws on 15- to 17-year-old motor vehicle crash mortality for all 50 states from 1999 to 2015. METHODS: Prospective data on motor vehicle fatalities, crash characteristics, state driving laws, and American College of Surgeons-verified trauma centers were collected from publicly available sources for 50 US states from 1999 to 2015. A mixed fixed/random effects multivariate regression model was fitted to assess the relative contribution of crash characteristics, state laws, and vPTCs while controlling for state variation and time trends. RESULTS: The final regression model included driver and crash characteristics, verified trauma centers, and state laws. Camera laws ([B = -0.57 [p < 0.001]) were associated with a 57% decrease in the rate of change in adolescent crude fatalities. The lagged Level 1 vPTC crude rate (B = 0.12 [p < .001]) was protective and contributed independently to a 12% decline in the rate of change in teen fatalities over the time period. Seat belt laws (B = 0.15 [p < 0.001]), graduated driver's license passenger restrictions (B = -0.07[p < 0.001]), graduated driver's license learner permit period (B = -0.04 [p < 0.002]), nondeployed airbag (B = -0.003 [p < 0.001]), and Hispanic heritage (B = 0.003 [p < 0.05]) were protective. Increased risk of fatality was associated with minivan (B = 0.01 [p < 0.001]), speed > 90 mph (B = 0.004 [p < 0.001]), rural roads (B = 0.002 [p < 0.002], unknown seat belt compliance (B = 0.004 [p < 0.001]), and dry road surface (B = 0.005 [p < 0.001]). CONCLUSIONS: State camera laws during the study time frame are associated with a 57% decrease in the rate of change in adolescent crude fatalities; vPTCs during the study time period reduced overall rate of change in the crude fatality rate by 12%. State laws, restrictions on teenage passengers and longer learner's permit periods, and seat belt laws are associated with significant decreases in the crude teen mortality rate. LEVEL OF EVIDENCE: Prospective study and prevention, level III. PMID- 29787528 TI - Increased trauma activation is not equally beneficial for all elderly trauma patients. AB - BACKGROUND: Physiologic changes in the elderly lead to higher morbidity and mortality after injury. Increasing level of trauma activation has been proposed to improve geriatric outcomes, but the increased cost to the patient and stress to the hospital system are significant downsides. The purpose of this study was to identify the age at which an increase in activation status is beneficial. METHODS: A retrospective review of trauma patients 70 years or older from October 1, 2011, to October 1, 2016, was performed. On October 1, 2013, a policy change increased the activation criteria to the highest level for patients 70 years or older with a significant mechanism of injury. Patients who presented prior to (PRE) were compared with those after the change (POST). Data collected included age, Injury Severity Score (ISS), length of stay (LOS), complications, and mortality. Primary outcome was mortality, and secondary outcome was LOS. Multivariable regressions controlled for age, ISS, injury mechanism, and number of complications. RESULTS: A total of 4,341 patients met the inclusion criteria, 1,919 in PRE and 2,422 in POST. Mean age was 80.4 and 81 years in PRE and POST groups, respectively (p = 0.0155). Mean ISS values were 11.6 and 12.4 (p < 0.0001) for the PRE and POST groups. POST had more Level 1 activations (696 vs. 220, p < 0.0001). After controlling for age, ISS, mechanism of injury, and number of complications, mortality was significantly reduced in the POST group 77 years or older (odds ratio, 0.53; 95% confidence interval, 0.3-0.87) (Fig. 1). Hospital LOS was significantly reduced in the POST group age 78 years or older (regression coefficient, -0.55; 95% confidence interval, -1.09 to -0.01) (Fig. 2). CONCLUSIONS: This study suggests geriatric trauma patients 77 years or older benefit from the highest level of trauma activation with shorter LOS and lower mortality. A focused approach to increasing activation level for elderly patients may decrease patient cost. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV. PMID- 29787527 TI - An AAST-MITC analysis of pancreatic trauma: Staple or sew? Resect or drain? AB - INTRODUCTION: Pancreatic trauma results in high morbidity and mortality, in part caused by the delay in diagnosis and subsequent organ dysfunction. Optimal operative management strategies remain unclear. We therefore sought to determine CT accuracy in diagnosing pancreatic injury and the morbidity and mortality associated with varying operative strategies. METHODS: We created a multicenter, pancreatic trauma registry from 18 Level 1 and 2 trauma centers. Adult, blunt or penetrating injured patients from 2005 to 2012 were analyzed. Sensitivity and specificity of CT scan identification of main pancreatic duct injury was calculated against operative findings. Independent predictors for mortality, adult respiratory distress syndrome (ARDS), and pancreatic fistula and/or pseudocyst were identified through multivariate regression analysis. The association between outcomes and operative management was measured. RESULTS: We identified 704 pancreatic injury patients of whom 584 (83%) underwent a pancreas related procedure. CT grade modestly correlated with OR grade (r 0.39) missing 10 ductal injuries (9 grade III, 1 grade IV) providing 78.7% sensitivity and 61.6% specificity. Independent predictors of mortality were age, Injury Severity Score (ISS), lactate, and number of packed red blood cells transfused. Independent predictors of ARDS were ISS, Glasgow Coma Scale score, and pancreatic fistula (OR 5.2, 2.6-10.1). Among grade III injuries (n = 158, 22.4%), the risk of pancreatic fistula/pseudocyst was reduced when the end of the pancreas was stapled (OR 0.21, 95% CI 0.05-0.9) compared with sewn and was not affected by duct stitch placement. Drainage alone in grades IV (n = 25) and V (n = 24) injuries carried increased risk of pancreatic fistula/pseudocyst (OR 8.3, 95% CI 2.2-32.9). CONCLUSION: CT is insufficiently sensitive to reliably identify pancreatic duct injury. Patients with grade III injuries should have their resection site stapled instead of sewn and a duct stitch is unnecessary. Further study is needed to determine if drainage alone should be employed in grades IV and V injuries. LEVEL OF EVIDENCE: Epidemiologic/Diagnostic study, level III. PMID- 29787529 TI - Motor vehicle crash fatalaties and undercompensated care associated with legalization of marijuana. AB - BACKGROUND: Half of the US states have legalized medical cannabis (marijuana), some allow recreational use. The economic and public health effects of these policies are still being evaluated. We hypothesized that cannabis legalization was associated with an increase in the proportion of motor vehicle crash fatalities involving cannabis-positive drivers, and that cannabis use is associated with high-risk behavior and poor insurance status. METHODS: Hawaii legalized cannabis in 2000. Fatality Analysis Reporting System data were analyzed before (1993-2000) and after (2001-2015) legalization. The presence of cannabis (THC), methamphetamine, and alcohol in fatally injured drivers was compared. Data from the state's highest level trauma center were reviewed for THC status from 1997 to 2013. State Trauma Registry data from 2011 to 2015 were reviewed to evaluate association between cannabis, helmet/seatbelt use, and payor mix. RESULTS: THC positivity among driver fatalities increased since legalization, with a threefold increase from 1993-2000 to 2001-2015. Methamphetamine, which has remained illegal, and alcohol positivity were not significantly different before versus after 2000. THC-positive fatalities were younger, and more likely, single vehicle accidents, nighttime crashes, and speeding. They were less likely to have used a seatbelt or helmet. THC positivity among all injured patients tested at our highest level trauma center increased from 11% before to 20% after legalization. From 2011 to 2015, THC-positive patients were significantly less likely to wear a seatbelt or helmet (33% vs 56%). They were twice as likely to have Medicaid insurance (28% vs 14%). CONCLUSION: Since the legalization of cannabis, THC positivity among MVC fatalities has tripled statewide, and THC positivity among patients presenting to the highest level trauma center has doubled. THC-positive patients are less likely to use protective devices and more likely to rely on publically funded medical insurance. These findings have implications nationally and underscore the need for further research and policy development to address the public health effects and the costs of cannabis related trauma. LEVEL OF EVIDENCE: Prognostic, level III. PMID- 29787530 TI - CRISIS UNDER THE RADAR: ILLICIT AMPHETAMINE USE IS REACHING EPIDEMIC PROPORTIONS AND CONTRIBUTING TO RESOURCE OVER-UTILIZATION AT A LEVEL 1 TRAUMA CENTER. AB - INTRODUCTION: Trauma centers reported illicit amphetamine use in approximately 10% of trauma admissions in the previous decade. From experience at a trauma center located in a southwestern metropolis, our perception is that illicit amphetamine use is on the rise, and that these patients utilize in-hospital resources beyond what would be expected for their injuries. The purpose of this study was to document the incidence of illicit amphetamine use among our trauma patients and to evaluate its impact on resource utilization. METHODS: We conducted a retrospective cohort study using 7 consecutive years of data (starting July 2010) from our institution's trauma registry. Toxicology screenings were used to categorize patients into one of three groups: illicit amphetamine, other drugs, or drug free. Adjusted linear and logistic regression models were used to predict hospital cost, length of stay, ICU admission and ventilation between drug groups. Models were conducted with combined injury severity (ISS) and then repeated for ISS <9, ISS 9-15 and ISS 16 and above. RESULTS: 8,589 patients were categorized into the following three toxicology groups: 1255 (14.6%) illicit amphetamine, 2214 (25.8%) other drugs, and 5120 (59.6%) drug free. Illicit amphetamine use increased threefold over the course of the study (from 7.85% to 25.0% of annual trauma admissions). Adjusted linear models demonstrated that illicit amphetamine among patients with ISS<9 was associated with 4.6% increase in hospital cost (P=.019) and 7.4% increase in LOS (P=.043). Logistic models revealed significantly increased odds of ventilation across all ISS groups and increased odds of ICU admission when all ISS groups were combined (P=.001) and within the ISS<9 group (P=.002). CONCLUSION: Hospital resource utilization of amphetamine patients with minor injuries is significant. Trauma centers with similar epidemic growth in proportion of amphetamine patients face a potentially significant resource strain relative to other centers. STUDY TYPE: Prognostic and Epidemiological LEVEL OF EVIDENCE: III. PMID- 29787531 TI - Blunt traumatic scapular fractures are associated with great vessel injuries in children. AB - BACKGROUND: Patients with stable blunt great vessel injury (GVI) can have poor outcomes if the injury is not identified early. With current pediatric trauma radiation reduction efforts, these injuries may be missed. As a known association between scapular fracture and GVI exists in adult blunt trauma patients, we examined whether that same association existed in pediatric blunt trauma patients. METHODS: Bluntly injured patients younger than 18 years old were identified from 2012 to 2014 in the National Trauma Data Bank. Great vessel injury included all major thoracic vessels and carotid/jugular. Demographics of patients with and without scapular fracture were compared with descriptive statistics. The chi test was used to examine this association using SAS Version 9.4 (SAS Institute, Inc, Cary, NC). RESULTS: We found a significant association between pediatric scapular fracture and GVI. Of 291,632 children identified, 1,960 had scapular fractures. Children with scapular fracture were 10 times more likely to have GVI (1.2%) compared to those without (0.12%, p < 0.0001). Most common GVI seen were carotid artery, thoracic aorta, and brachiocephalic or subclavian artery or vein. Children with both scapular fracture and GVI were most commonly injured by motor vehicles (57% collision, 26% struck). CONCLUSIONS: Injured children with blunt scapular fracture have a 10-fold greater risk of having a GVI when compared to children without scapular fracture. Presence of blunt traumatic scapular fracture should have appropriate index of suspicion for a significant GVI in pediatric trauma patients. LEVEL OF EVIDENCE: Epidemiologic and prognostic study, level III; Therapeutic, level IV. PMID- 29787532 TI - Do screening and a randomized brief intervention at a Level 1 trauma center impact acute stress reactions to prevent later development of posttraumatic stress disorder? AB - BACKGROUND: Approximately 20% to 40% of trauma survivors experience posttraumatic stress disorder (PTSD). The American College of Surgeons Committee on Trauma reports that early screening and referral has the potential to improve outcomes and that further study of screening and intervention for PTSD would be beneficial. This prospective randomized study screened hospitalized patients for traumatic stress reactions and assessed the effect of a brief intervention in reducing later development of PTSD. METHODS: The Primary Care PTSD (PC-PTSD) screen was administered to admitted patients. Patients with symptoms were randomized to an intervention or control group. The brief intervention focused on symptom education and normalization, coping strategies, and utilizing supports. The control group received a 3-minute educational brochure review. Both groups completed in-hospital interviews, then 45- and 90-day telephone interviews. Follow-up collected the PTSD checklist-civilian (PCL-C) assessment and qualitative data on treatment-seeking barriers. RESULTS: The PC-PTSD screen was successful in predicting later PTSD symptoms at both 45 days (beta = 0.43, p < 0.001) and 90 days (beta = 0.37, p < 0.001) even after accounting for depression. Correlations of the intervention with the PCL-C scores and factor score estimates did not reach statistical significance at either time point (p = 0.827; p = 0.838), indicating that the brief intervention did not decrease PTSD symptoms over time. Of those at or above the PCL-C cutoff at follow-ups, a minority had sought treatment for their symptoms (43.2%). Primary barriers included focusing on their injury or ongoing rehabilitation, financial concerns, or location of residence. CONCLUSION: The PC-PTSD screen identified patients who later assess positive for PTSD using the PCL-C. The brief intervention did not reduce 45- and 90-day PTSD development. Follow-up interviews revealed lack of treatment infrastructure in the community. It will be important for trauma centers to align with community resources to address the treatment needs of at-risk patients. LEVEL OF EVIDENCE: Prospective randomized controlled trial, level II. PMID- 29787533 TI - High-volume hospitals are associated with lower mortality among high-risk emergency general surgery patients. AB - INTRODUCTION: We have previously demonstrated that Emergency General Surgery (EGS) patients treated at high-volume hospitals experience lower mortality rates than those treated at low-volume hospitals. However, EGS comprises a wide spectrum of diseases. Our goal was to determine which EGS diseases had better outcomes at high-volume hospitals. METHODS: We undertook a retrospective analysis of the National Inpatient Sample database for 2013 (a nationwide representative sample). Patients with EGS diseases were identified using American Association for the Surgery of Trauma definitions. A hierarchical logistic regression model was used to measure risk-adjusted probability of death, adjusting for age, sex, race, ethnicity, insurance type, and comorbidities. Patients were then grouped into 16 risk groups based upon their predicted probability of death. We then compared observed mortality rates at high- versus low-volume hospitals within each risk group. RESULTS: Nationwide, 3,006,615 patients with EGS diseases were treated at 4,083 hospitals in 2013. Patients with predicted risk of death of 4% or higher (275,615 patients, 9.2%) had lower observed mortality rates at high volume hospitals than at low-volume hospitals (7.7% vs. 10.2%, p < 0.001). We estimated that 1,002 deaths were potentially preventable if high-risk patients who were treated at low-volume hospitals were instead transferred to high-volume hospitals. CONCLUSION: EGS patients with predicted risk of death of 4% or higher experience lower mortality rates at high-volume hospitals than at low-volume hospitals. A regional system of EGS care that enables rapid transfer of high-risk patients to high-volume hospitals may prevent several deaths. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III; Therapeutic/Case Management, level IV. PMID- 29787534 TI - A metal organic framework reduces thrombus formation and platelet aggregation ex vivo. AB - BACKGROUND: Management of hemostasis is a key challenge during extracorporeal life support (ECLS). Metal organic frameworks are being investigated for use as nitric oxide (NO) catalysts for incorporation into ECLS circuitry to prevent thrombosis at the blood-biomaterial interface. A specific metal organic framework, CuBTTri, has been shown to accelerate NO release from bioavailable donors like S-nitrosoglutathione (GSNO). We hypothesized that CuBTTri would reduce thrombus formation in whole blood (WB) and inhibit platelet aggregation. METHODS: CuBTTri particles were added to WB and analyzed by thromboelastography. Biostable metal-based frameworks (MIL-100, Zeolite USY) were added to blood as controls, in addition to a saline vehicle control. Reaction time (R), clot formation time (K), alpha-angle, clot strength (MA), and percent fibrinolysis (LY30/LY60) were recorded. The effect of CuBTTri on platelet aggregation was assessed in WB and platelet-rich plasma (PRP), both with and without addition of GSNO. RESULTS: CuBTTri significantly prolonged R and K and decreased alpha-angle and MA relative to the metal framework controls. Dose escalation results suggest that the control metal-based particles induce thrombus formation, as R and K were significantly reduced compared with the saline control; however, this did not occur in the CuBTTri group. LY30/LY60 were elevated in the CuBTTri group versus saline (p = 0.014) but were not different from metal framework controls. CuBTTri alone and with GSNO reduced platelet aggregation in WB (p < 0.0001), whereas GSNO alone had no effect. In PRP, GSNO and CuBTTri inhibited platelet aggregation separately, and together decreased aggregation by 35% relative to GSNO alone (p = 0.004). CONCLUSIONS: CuBTTri reduced thrombus formation and inhibited platelet aggregation. CuBTTri enhanced platelet inhibition with GSNO, which was consistent with reports that CuBTTri accelerates NO release from endogenous NO donors. This initial characterization of CuBTTri demonstrated its potential as an antithrombogenic agent to be further evaluated with incorporation into ECLS circuitry. PMID- 29787535 TI - Can acute care surgeons perform while fatigued? An EAST multicenter study. AB - BACKGROUND: Fatigued surgeon performance has only been assessed in simulated sessions or retrospectively after a night on call. We hypothesized that objectively assessed fatigue of acute care surgeons affects patient outcome. METHODS: Five acute care surgery services prospectively identified emergency cases over 27 months. Emergency cases were defined by the surgeon identifying the patient as requiring immediate operation upon consultation or admission. Within 48 hours, surgeons reported sleep time accumulated before operation, if nonclinical delays to operation occurred, and patient volume during the shift. To maximize differences, fatigued surgeons were defined as performing a case after midnight without having slept in the prior 18 hours. Rested surgeons performed cases at or before 8 PM or after at least 3 hours of sleep before operation. A four-level ordinal scale was used to assign case complexity. Hierarchical logistic regression models were constructed to assess the impact of fatigue on mortality and major morbidity while controlling for center and patient level factors. RESULTS: Of 882 cases collected, 611 met criteria for fatigue or rested. Of these cases, 370 were performed at night and 182 by a fatigued surgeon. Rested surgeons were more likely to be operating on an older or female patient; other characteristics were similar. Mortality and major morbidity were similar between fatigued and rested surgeons (12.1% vs 12.1% and 46.9% vs 48.9%), respectively. After controlling for center and patient factors, surgeon fatigue did not affect mortality or major morbidity. Mortality variance was 6.30% and morbidity variance was 7.02% among centers. CONCLUSION: Acute care surgeons have similar outcomes in a fatigued or rested state. Work schedules for acute care surgeons should not be adjusted to shifts less than 24 hours for the sole purpose of improving patient outcomes. LEVEL OF EVIDENCE: Prognostic study, level IV. PMID- 29787536 TI - A meta-analysis of the incidence of complications associated with groin access after the use of resuscitative endovascular balloon occlusion of the aorta in trauma patients. AB - BACKGROUND: Serious complications related to groin access have been reported with the use of resuscitative endovascular balloon occlusion of the aorta (REBOA). We performed a systematic review and meta-analysis to estimate the incidence of complications related to groin access from the use of REBOA in adult trauma patients. METHODS: We identified articles in MEDLINE and EMBASE. We reviewed all studies that involved adult trauma patients who underwent the placement of a REBOA and included only those that reported the incidence of complications related to groin access. A meta-analysis of proportions was performed. RESULTS: We identified 13 studies with a total of 424 patients. REBOA was inserted most commonly by trauma surgeons or emergency room physicians. Information regarding puncture technique was reported in 12 studies and was available for a total of 414 patients. Percutaneous access and surgical cutdown were performed in 304 (73.4%) and 110 (26.5%) patients, respectively. Overall, complications related to groin access occurred in 5.6% of patients (n = 24/424). Lower limb amputation was required in 2.1% of patients (9/424), of which three cases (3/424 [0.7%]) were directly related to the vascular puncture from the REBOA insertion. A meta analysis that used the logit transformation showed a 5% (95% CI 3%-9%) incidence of complications without significant heterogeneity (LR test: chi = 0.73, p = 0.2, Tau-square = 0.2). In a second meta-analysis, we used the Freeman-Tukey double arcsine transformation and found an incidence of complications of 4% (95% CI 2% 7%) with low heterogeneity (I = 16.3%). CONCLUSION: We found that the incidence of complications related to groin access was of 4-5% based on a meta-analysis of 13 studies published worldwide. Currently, there are no benchmarks or quality measures as a reference to compare, and thus, further work is required to identify these benchmarks and improve the practice of REBOA in trauma surgery. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III. PMID- 29787537 TI - "It is a sin to be good when you were sent to be great: Quality in trauma care". PMID- 29787538 TI - Intrathoracic transmural esophageal perforation (Boerhaave's syndrome): Challenges in management of the delayed presentation. PMID- 29787539 TI - A concomitant bone fracture delays cognitive recovery from traumatic brain injury. AB - BACKGROUND: Brain injury progression after severe traumatic brain injury (TBI) is associated with worsening cerebral inflammation but it is unknown how a concomitant bone fracture (BF) affects this progression. Enoxaparin (ENX) decreases penumbral leukocyte mobilization after TBI and improves neurologic recovery. We hypothesized that a concomitant BF worsens learning/memory recovery weeks after TBI and that ENX improves this recovery. METHODS: CD1 male mice underwent controlled cortical impact or sham craniotomy with or without tibial fracture, receiving either daily ENX (0.8 mg/kg) or saline for 14 days after injury. Randomization defined four groups (Sham, TBI only, TBI + Fx, TBI + Fx + ENX, n = 5/each). Body weight loss and neurologic recovery (Garcia Neurologic Test, max score = 18) were assessed each day. Mouse learning (swimming time [s] and total distance [m] to reach the submerged platform Days 14 to 17 after TBI) and memory (swimming time [s] in platform quadrant after platform removed [probe]) was assessed by the Morris water maze. Ly-6G (cerebral neutrophil sequestration) and glial fibrillary acidic protein were evaluated by immunohistochemistry in brain tissue post mortem. Analysis of variance with Tukey's post hoc test determined significance (p < 0.05). RESULTS: A concurrent BF worsened Garcia Neurologic Test scores post-TBI Days 2 to 4 (p < 0.01) as compared with TBI only, and ENX reversed this worsening on Day 4 (p < 0.01). Learning was significantly slower (greater swimming time and distance) in TBI + Fx versus TBI only on Day 17 (p < 0.01). This was despite similar swimming velocities in both groups, indicating intact extremity motor function. Memory was similar in isolated TBI and Sham which was significantly better than in TBI + Fx animals (p < 0.05). Glial fibrillary acidic protein-positive cells in penumbral cortex were most prevalent in TBI + Fx animals, significantly greater than in Sham (p < 0.05). CONCLUSION: A long BF accompanying TBI worsens early neurologic recovery and subsequent learning/memory. Enoxaparin may partially counter this and improve neurologic recovery. PMID- 29787540 TI - Rib fractures fixation: Always worthwhile? PMID- 29787541 TI - Validation of predictive equations to assess energy expenditure in acute spinal cord injury. AB - BACKGROUND: Acute spinal cord injury (SCI) is devastating with morbidities compounded by inadequate nutrition. The American Society for Parenteral and Enteral Nutrition recommends indirect calorimetry (IC) to evaluate energy needs in SCI because no predictive energy equations have been validated. We sought to determine the accuracy of predictive equations to predict measured energy expenditure (MEE). METHODS: A retrospective review was performed over 2 years. Patients 18 years or older with cervical SCI who received IC were included. Height, weight, maximum temperature and minute ventilation on day of IC, plus MEE and VCO2 from IC were obtained. Predicted energy expenditure (PEE) was calculated using Harris-Benedict (HB), Penn State (PS), Mifflin St. Jeor (MSJ), Weir, Ireton Jones (IJ), and 25 kcal/kg formulas. MEE was then compared to the PEE of each method. RESULTS: Thirty-nine IC studies were completed for 20 patients. Weir had the strongest correlation to MEE (r = 0.98), followed by PS (r = 0.82). Correlations were similar among HB (r = 0.78), MSJ (r = 0.75), and IJ (r = 0.73), and weakest with 24 kcal/kg (r = 0.55). All had a p value <0.001. Deming regression confirmed strong correlations between Weir and PS to MEE, with coefficients of 1.03 and 1.515 (p < 0.001), respectively. Other formulas had comparatively higher coefficients and standard errors. Bland-Altman analysis confirmed Weir had the narrowest range of difference, with a mean difference of 25.5 kcal/day, followed by PS (-336.1 kcal/day). CONCLUSIONS: Weir is the best predictive energy equation, with all statistical tests demonstrating a strong correlation between MEE and Weir. The second best predictive equation is the Penn State formula, which predicts actual MEE measured by IC with high accuracy. LEVEL OF EVIDENCE: Diagnostic study, level III. PMID- 29787542 TI - Hemorrhagic shock alters fracture callus composition and activates the IL6 and RANKL/OPG pathway in mice. AB - BACKGROUND: Fracture and hemorrhagic shock often lead to impaired fracture healing. To elucidate underlying pathogenesis, this study aimed to analyze histological properties during fracture healing after hemorrhagic shock and involved signaling pathways in mice. METHODS: Male C57BL/6NCrl mice were assigned into five groups. Control group underwent no interventions. Sham group had a catheter and external fixator but neither blood loss nor osteotomy. Trauma hemorrhage (TH) group received a pressure-controlled hemorrhagic shock; osteotomy (Fx) group, an osteotomy and fixator; and combined trauma (THFx) group, both hemorrhagic shock and externally fixed osteotomy. After 1, 2, 3, and 4 weeks, the animals were killed. Undecalcified bones were analyzed histologically and signaling pathways relevant for fracture healing by polymerase chain reaction and Western blot. Statistical significance was set at 0.05 or less. Comparisons were performed using the Mann-Whitney U or Kruskal-Wallis test. RESULTS: In the THFx group, a decreased bone formation after 3 weeks, a reduction of both bone and cartilage after 2 weeks, and an enhanced activation of the RANKL/OPG and IL6 signaling pathway after 1 week were shown in comparison to Fx. CONCLUSIONS: Hemorrhagic shock has a retarding effect on fracture healing in the early phase of fracture healing and leads to activation of the IL6 and RANKL/OPG signaling pathways. PMID- 29787543 TI - Using clinical analysis to classify 30-day trauma readmissions. AB - BACKGROUND: Unplanned hospital readmissions are common across specialties. Descriptive readmission studies commonly query large administrative databases, which some speculate lack clinical granularity. This article provides the framework for a process improvement initiative aimed at identifying clinically meaningful reasons for trauma readmission. Our study hypothesizes an expected difference between the clinically abstracted reasons for readmission and those documented by the data processing staff in the trauma registry and that those differences will be the starting point to target performance improvement. METHODS: This is a retrospective, cohort study from 2014 to 2016 involving 18,998 trauma evaluations at a Level I trauma center. The systematic categorization of trauma readmissions was completed via clinical chart review. Readmissions were categorized following an organizational flowchart. The chart reviews ultimately resulted in two readmission categories: primary and secondary reasons for 30-day trauma readmission. RESULTS: There were 413 readmissions, an overall readmission rate of 2.7%. The highest rate of readmission, by mechanism of injury, was gunshot wounds (11%). Secondary reasons for readmission predominated (76.1%). Complications led (41%), followed by observation (8.8%) and pain (8.6%). Following readmission chart review and categorization, the trauma registry data were queried and categorized via the same method. When the two methods of data collection were compared, there was a significant difference (p < 0.0001). CONCLUSIONS: The granular dissection of readmission charts proved to assist in isolating clinically significant readmission variables, providing clarity into the reasons behind trauma readmission. If determined solely by the trauma registry data, our performance and quality improvement initiatives would be misguided. We recommend clinical oversight of databases, with clinical review of key areas in order to guide performance improvement. PMID- 29787544 TI - A clinical prediction model for raised intracranial pressure in patients with traumatic brain injuries. AB - BACKGROUND: Intracranial hypertension is believed to contribute to secondary brain insult in traumatically brain injured patients. Currently, the diagnosis of intracranial hypertension requires intracranial monitoring or advanced imaging. Unfortunately, prehospital transport times can be prolonged, delaying time to the initial radiographic assessment. The aim of this study was to identify clinical variables associated with raised intracranial pressure (ICP) prior to the completion of neuroimaging. METHODS: We performed a retrospective cohort study of head injured patients over a 3-year period. Patients were labeled as having increased ICP if they had a single reading of ICP greater than 20 mm Hg within 1 hour of ICP monitor insertion or computed tomography findings suggestive of raised ICP. Patient and clinical characteristics were analyzed using stepwise multivariable logistic regression with ICP as the dependent variable. RESULTS: Of 701 head injured patients identified, 580 patients met inclusion criteria. Mean age was 48.65 +/- 21 years, 73.3% were male. The mean Injury Severity Score was 22.71 +/- 12.38, and the mean Abbreviated Injury Scale for body region head was 3.34 +/- 1.06. Overall mortality was 14.7%. Only 46 (7.9%) patients had an ICP monitor inserted; however, a total of 107 (18%) patients met the definition of raised ICP. The mortality rate for patients with raised ICP was 50.4%. Independent predictors of raised ICP were as follows: age, older than 55 years (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.35-3.76), pupillary fixation (OR, 5.76; 95% CI, 3.16-10.50), signs of significant head trauma (OR, 2.431; 95% CI, 1.39-4.26), and need for intubation (OR, 3.589; 95% CI, 2.10 6.14). CONCLUSION: This study identified four independent variables associated with raised ICP and incorporated these findings into a preliminary risk assessment scale that can be implemented at the bedside to identify patients at significant risk of raised ICP. Future work is needed to prospectively validate these findings prior to clinical implementation. LEVEL OF EVIDENCE: Prognostic, Epidemiological, level III. PMID- 29787545 TI - Recent advances in austere combat surgery: Use of aortic balloon occlusion as well as blood challenges by special operations medical forces in recent combat operations. AB - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) for control of noncompressible torso hemorrhage is a technology that is increasingly being utilized in the combat casualty setting. Its use in the resource restricted environment holds potential to improve hemorrhage control, decrease blood product utilization, decrease morbidity, and improve combat mortality. The objective of this report is to present the single largest series of REBOA use on severely injured combat casualties. METHODS: Over an 18-month period, austere surgical teams comprised of coalition partners provided initial damage control resuscitation (DCR) and surgical stabilization for over 2,300 combat casualties prior to transferring patients to the next level of trauma care. RESULTS: Twenty patients presented with injuries from explosion and gunshot wounds with mean initial heart rate of 129 bpm and mean initial systolic blood pressure of 71 mm Hg. Femoral cutdowns were used in six patients. Aortic occlusion was achieved with REBOA catheter placement in Zone 1 (n = 17) and Zone 3 (n = 2). Systolic blood pressure increased an average of 56 mm Hg with aortic occlusion. There were no access related site complications. All patients survived transport to the next level of care. The majority of blood products transfused in this cohort were whole blood, largely supported by emergent blood drives. CONCLUSION: This series demonstrates the potential for REBOA as a lifesaving technique for the patient who presents with hemodynamic instability and noncompressible torso hemorrhage. Resuscitative endovascular balloon occlusion of the aorta allows austere surgical teams to rapidly stabilize severely injured combat casualties, expand capability, and provide enhanced DCR while minimizing personnel, resources, and blood product utilization. The use of "whole blood only" strategy for DCR shows potential to be superior to traditional component therapy, and when combined with "proactive" REBOA utilization, provides significant improvements in hemodynamics and hemorrhage control. LEVEL OF EVIDENCE: Case series, level V. PMID- 29787546 TI - Selective nonoperative management of pharyngoesophageal injuries secondary to penetrating neck trauma: A single-center review of 86 cases. AB - BACKGROUND: This article describes our experience with penetrating pharyngoesophageal injuries (PEI) in the light of a selective conservative approach, and has the objective to define criteria for nonoperative management (NOM). METHODS: This retrospective single-center review of patients with penetrating neck injury treated for confirmed PEI over a 6-year period aimed to test our proposed hypothesis that NOM is safe for hemodynamically stable patients with PEI, who have no competing indications for exploration, have no established sepsis, and who have a water-soluble contrast swallow either showing no- or a contained extravasation. RESULTS: Eighty-six (9%) patients with PEI (oropharynx, 17; hypopharynx, 40; esophagus, 29) of 948 patients with penetrating neck injury were included. Of the cohort 38 (44%) underwent NOM (oropharynx, 15 [88%]; hypopharynx, 18 [45%]; esophagus, 5 [17%]), and 48 (56%) were managed operatively. The median length of stay was 12 days (interquartile range, 19-8). Fifteen (17%) had a persistent leak and six (7%) mediastinitis. Five (6%) patients died but only one (1%) had isolated PEI. Retrospectively, 27 patients fulfilled our proposed criteria for NOM of which 23 had been treated actively by NOM (oropharynx, 8; hypopharynx, 12; esophagus, 3). For these patients, the length of stay was 10.0 days (interquartile range, 13-6), and none developed deep wound sepsis, mediastinitis, persistent leaks, or died. Of the remaining patients treated by NOM without fulfilling the proposed criteria, two were palliated (esophagus) and 13 were managed actively (oropharynx, 7; hypopharynx, 6). Only four of these patients (oropharynx, 1; hypopharynx, 3) were assessed with water soluble contrast swallow, which showed noncontained extravasation, and three complicated with persistent leaks. CONCLUSION: Nonoperative management of PEI is safe for a carefully selected subgroup of patients. However, most injuries to the caudal part of the cervical digestive tract mandate urgent exploration. LEVEL OF EVIDENCE: Clinical Management Study, Level V evidence. PMID- 29787547 TI - Interrupted versus continuous fascial closure in patients undergoing emergent laparotomy: A randomized controlled trial. AB - BACKGROUND: The optimal method of fascial closure, interrupted fascial closure (IFC) versus continuous fascial closure (CFC) has never been studied exclusively in the setting of emergency surgery. We hypothesized that IFC decreases postoperative incisional hernia development following emergent laparotomies. METHODS: Between August 2008 and September 2015, patients undergoing emergent laparotomies were consented and randomly assigned to either IFC or CFC. Patients were followed up postoperatively for at least 3 months and assessed for incisional hernia, dehiscence, or wound infection. We excluded those with trauma, elective surgery, mesh in place, primary ventral hernia, previous abdominal surgery within 30 days, or those not expected to survive for more than 48 hours. Our primary endpoint was the incidence of postoperative incisional hernias. RESULTS: One hundred thirty-six patients were randomly assigned to IFC (n = 67) or CFC (n = 69). Baseline characteristics were similar between the groups. No difference was noted in the length of the abdominal incision, or the peak inspiratory pressure after the closure. The median time needed for closure was significantly longer in the IFC group (22 minutes vs. 13 minutes, p < 0.001). Thirty-seven (55.2%) IFC and 41 (59.4%) CFC patients completed their follow-up visits. There was no statistically significant difference in baseline and intraoperative characteristics between those who completed follow-ups and those who did not. The median time from the day of surgery to the day of the last follow-up was similar between IFC and CFC (233 days vs. 216 days, p = 0.67), as were the rates of incisional hernia (13.5% versus 22.0%, p = 0.25), dehiscence (2.7% vs. 2.4%, p = 1.0), and surgical site infection (16.2% vs. 12.2%, p = 0.75). CONCLUSION: There was no statistically detectable difference in postoperative hernia development between those undergoing IFC versus CFC after emergent laparotomies. However, this may be due to the relatively low sample size. LEVEL OF EVIDENCE: Therapeutic/Care Management Study, level III. PMID- 29787548 TI - A subset of five human mitochondrial formyl peptides mimics bacterial peptides and functionally deactivates human neutrophils. AB - BACKGROUND: Trauma causes inflammation by releasing mitochondria that act as Danger-Associated Molecular Patterns (DAMPs). Trauma also increases susceptibility to infection. Human mitochondria contain 13 N-formyl peptides (mtFPs). We studied whether mtFPs released into plasma by clinical injury induce neutrophil (PMN) inflammatory responses, whether their potency reflects their similarity to bacterial FPs and how their presence at clinically relevant concentration affects PMN function. METHODS: N-terminal sequences of the 13 mtFPs were synthesized. Changes in human PMN cytosolic Ca concentration ([Ca]i) and chemotactic responses to mtFPs were studied. Sequence similarity of mtFPs to the canonical bacterial peptide f-Met-Leu-Phe (fMLF/fMLP) was studied using the BLOcks SUbstitution Matrix 62 (BLOSUM 62) system. The presence of mtFPs in plasma of trauma patients was assayed by Enzyme-linked immunosorbent assay (ELISA). The effects of the most potent mtFP (ND6) on PMN signaling and function were then studied at ambient clinical concentrations by serial exposure of native PMN to ND6, chemokines and leukotrienes. RESULTS: Five mtFPs (ND6, ND3, ND4, ND5, and Cox 1) induced [Ca]i flux and chemotaxis in descending order of potency. Evolutionary similarity to fMLF predicted [Ca]i flux and chemotactic potency linearly (R = 0.97, R = 0.95). Chemoattractant potency was also linearly related to [Ca]i flux induction (R = 0.92). Active mtFPs appear to circulate in significant amounts immediately after trauma and persist through the first week. The most active mtFP, ND6, suppresses responses to physiologic alveolar chemoattractants (CXCL-1, leukotriene B4) as well as to fMLF where CXCL-1 and leukotriene B4 do not suppress N-formyl peptide receptor (FPR)-1 responses to mtFPs. Prior FPR-1 inhibition rescues PMN from heterologous suppression of CXCR-1 and BLT-1 by mtFPs. CONCLUSION: The data suggest mtFPs released by injured tissue may attract PMN to trauma sites while suppressing PMN responses to other chemoattractants. Inhibition of mtFP-FPR1 interactions might increase PMN recruitment to lung bacterial inoculation after trauma. These findings suggest new paradigms for preventing infections after trauma. LEVEL OF EVIDENCE: Therapeutic, Level IV. PMID- 29787549 TI - Long-term, patient-centered outcomes of lower-extremity vascular trauma. AB - OBJECTIVE: To describe the long-term outcomes of military lower-extremity vascular injuries, and the decision making of surgeons treating these injuries. BACKGROUND: Lower-extremity vascular trauma is an important cause of preventable death and severe disability, and decisions on amputation or limb salvage can be difficult. Additionally, the complexity of the condition is not amenable to controlled study, and there is limited data to guide clinical decision making and establish sensible treatment expectations during rehabilitation. METHODS: A cohort study of 554 US service members who sustained lower-extremity vascular injury in Iraq or Afghanistan (March 2003 to February 2012) was performed using the military's trauma registry, its electronic health record, patient interviews, and quality-of-life surveys. Long-term surgical and functional outcomes, and the timing and rationale of surgical decisions, were analyzed. RESULTS: Of 579 injured extremities, 49 (8.5%) underwent primary amputation and 530 (91.5%) an initial attempt at salvage. Ninety extremities underwent secondary amputation, occurring in the early (n = 60; <30 days) or late (n = 30; >30 days) phases after injury. For salvage attempts, freedom from amputation 10 years after injury was 82.7% (79.1%-85.7%). Long-term physical and mental health outcomes were similar between service members who underwent reconstruction and those who underwent amputation. CONCLUSION: This military experience provides data that will inform an array of military and civilian providers who care for patients with severe lower-extremity injury. While the majority salvage attempts endure, success is hindered by ischemia and necrosis during the acute stage and pain, dysfunction and infection in the later phases of recovery. LEVEL OF EVIDENCE: Therapeutic/prognostic, level III. PMID- 29787550 TI - Timing of surgery and the risk of complications in patients with acute appendicitis: A population-level case-crossover study. AB - BACKGROUND: Delays in surgery for patients with acute appendicitis may increase the risk of perforation and complications. These risks must be balanced with the theoretical risk of nighttime operations. OBJECTIVE: To determine the effect of (i) time of day of surgery and (ii) time between triage presentation and surgery, on surgical complications in patient undergoing appendectomy for appendicitis. METHODS: Population level data from Ontario from 2009 to 2015 was used to conduct this retrospective cohort study. The primary exposure was (i) time of day of surgery and (ii) time between triage and surgery. The primary outcome was a composite outcome of perioperative complications. Conditional logistic regression adjusted for patient factors was used to estimate adjusted odds ratios (OR) between the exposure and complications. RESULTS: Twelve thousand nine hundred thirty-seven matched pairs (N = 25,874) of adult patients were included. Compared to day operations, the odds of complications were lower during the evening (OR, 0.90; 95% confidence interval [CI], 0.84-0.96) and no different at night (OR, 0.90; 95% CI, 0.77-1.04). The odds of complications were higher in patients who waited longer than 24 hours for surgery compared with those who waited less than 6 hours (OR, 1.27; 95% CI, 1.14-1.43) with no increased risk in those who waited 6 hours to 12 hours or 12 hours to 24 hours. CONCLUSION: This large population study is the first to assess surgical risks using a case-crossover design to account for the surgeon as a potential confounder. Nighttime surgery and delaying surgery up to 24 hours were not associated increased risks of complications. LEVEL OF EVIDENCE: Therapeutic, level III. PMID- 29787552 TI - Subtotal cholecystectomy as an effective and safe option for complicated cholecystitis: A 2018 EAST Master Class Video Presentation. PMID- 29787551 TI - Transfusion of cryopreserved platelets exacerbates inflammatory liver and lung injury in a mice model of hemorrhage. AB - BACKGROUND: Platelets are essential for primary hemostasis and also play an important role in inflammatory reactions. The hemostatic property of cryopreserved platelets (CPPs) has been confirmed in the treatment of bleeding casualties, but inflammatory injury induced by CPP transfusion is relatively unclear. We aim to investigate the effects of CPP transfusion on inflammatory organ injury in mice after hemorrhage. METHODS: Mice were subjected to a volume controlled hemorrhage over 1 hour, and then were transfused with fresh platelets (FPs), Liquid-stored platelets (LPPs), CPPs, or fresh frozen plasma (FFP, control). At 6 hours posttransfusion, mice were sacrificed, and blood and tissues were sampled. Tissue sections were examined histologically and by immunohistochemical staining of neutrophils and macrophages. Plasma alanine aminotransferase, hepatic myeloperoxidase activity and inflammatory cytokine levels were measured. RESULTS: Transfusion of stored platelets (LPPs and CPPs) caused more serious histological injury in liver and lung compared with FPs and FFP (p < 0.05). However, kidney histological injury was similar among groups. Significantly higher numbers of Ly-6G-positive neutrophils were detected in liver and of F4/80-positive macrophages in liver and lung of mice transfused with LPPs or CPPs compared with FPs or FFP (p < 0.05). Transfusion of CPPs caused the most severe inflammatory liver injury, as reflected by alanine aminotransferase levels, hepatic macrophage infiltration, and hepatic myeloperoxidase activity and inflammatory cytokine levels (macrophage inflammatory protein-2, tumor necrosis factor-alpha, and interleukin-1beta). CONCLUSION: Cryopreserved platelet transfusion is more likely to aggravate hemorrhage-induced liver and lung injury by activating macrophage and facilitating neutrophil infiltration into hepatic tissues. PMID- 29787553 TI - Logistics of air medical transport: When and where does helicopter transport reduce prehospital time for trauma? AB - BACKGROUND: Trauma is a time sensitive disease. Helicopter emergency medical services (HEMS) have shown benefit over ground emergency medical services (GEMS), which may be related to reduced prehospital time. The distance at which this time benefit emerges depends on many factors that can vary across regions. Our objective was to determine the threshold distance at which HEMS has shorter prehospital time than GEMS under different conditions. METHODS: Patients in the Pennsylvania trauma registry 2000 to 2013 were included. Distance between zip centroid and trauma center was calculated using straight-line distance for HEMS and driving distance from geographic information systems network analysis for GEMS. Contrast margins from linear regression identified the threshold distance at which HEMS had a significantly lower prehospital time than GEMS, indicated by nonoverlapping 95% confidence intervals. The effect of peak traffic times and adverse weather on the threshold distance was evaluated. Geographic effects across EMS regions were also evaluated. RESULTS: A total of 144,741 patients were included with 19% transported by HEMS. Overall, HEMS became faster than GEMS at 7.7 miles from the trauma center (p = 0.043). Helicopter emergency medical services became faster at 6.5 miles during peak traffic (p = 0.025) compared with 7.9 miles during off-peak traffic (p = 0.048). Adverse weather increased the distance at which HEMS was faster to 17.1 miles (p = 0.046) from 7.3 miles in clear weather (p = 0.036). Significant variation occurred across EMS regions, with threshold distances ranging from 5.4 to 35.3 miles. There was an inverse but non-significant relationship between urban population and threshold distance across EMS regions (rho, -0.351, p = 0.28). CONCLUSION: This is the first study to demonstrate that traffic, weather, and geographic region significantly impact the threshold distance at which HEMS are faster than GEMS. Helicopter emergency medical services was faster at shorter distances during peak traffic while adverse weather increased this distance. The threshold distance varied widely across geographic region. These factors must be considered to guide appropriate HEMS triage protocols. LEVEL OF EVIDENCE: Therapeutic, level IV. PMID- 29787554 TI - Western Trauma Association Critical Decisions in Trauma: Management of renal trauma. PMID- 29787555 TI - Implementation of a CT scan practice guideline for pediatric trauma patients reduces unnecessary scans without impacting outcomes. AB - INTRODUCTION: Computed tomography (CT) scans are useful in the evaluation of trauma patients, but are costly and pose risks from ionizing radiation in children. Recent literature has demonstrated the use of CT scan guidelines in the management of pediatric trauma. The study objective is to review our treatment of pediatric blunt trauma patients and evaluate CT use before and after CT-guideline implementation. METHODS: Our Pediatric Level 2 Trauma Center (TC) implemented a CT scan practice guideline for pediatric trauma patients in March 2014. The guideline recommended for or against CT of the head and abdomen/pelvis using published criteria from the Pediatric Emergency Care and Research Network. There was no chest CT guideline. We reviewed all pediatric trauma patients for CT scans obtained during initial evaluation before and after guideline implementation, excluding inpatient scans. The Trauma Registry Database was queried to include all pediatric (age < 15) trauma patients seen in our TC from 2010 to 2016, excluding penetrating mechanism and deaths in the TC. Scans were considered positive if organ injury was detected. Primary outcome was the proportion of patients undergoing CT and percent positive CTs. Secondary outcomes were hospital length of stay, readmissions, and mortality. Categorical and continuous variables were analyzed with chi and Wilcoxon rank-sum tests, respectively. p < 0.05 was considered significant. RESULTS: We identified 1,934 patients: 1,106 pre- and 828 post-guideline. Absolute reductions in head, chest, and abdomen/pelvis CT scans were 17.7%, 11.5%, and 18.8%, respectively (p < 0.001). Percent positive head CTs were equivalent, but percent positive chest and abdomen CT increased after implementation. Secondary outcomes were unchanged. CONCLUSIONS: Implementation of a pediatric CT guideline significantly decreases CT use, reducing the radiation exposure without a difference in outcome. Trauma centers treating pediatric patients should adopt similar guidelines to decrease unnecessary CT scans in children. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 29787556 TI - Unrealized potential of the US military battlefield trauma system: DOW rate is higher in Iraq and Afghanistan than in Vietnam, but CFR and KIA rate are lower. AB - LEVEL OF EVIDENCE: Observational/retrospective/historic controls, level IV. PMID- 29787557 TI - Extending the Golden Hour For Zone 1 Reboa: Improved Survival and Reperfusion Injury with Intermittent Versus Continuous Reboa in a Porcine Severe Truncal Hemorrhage Model. AB - BACKGROUND: Non-compressible hemorrhage can be controlled using resuscitative endovascular occlusion of the aorta (REBOA). Prolonged ischemia limits REBOA application during Zone 1 deployment. Intermittent inflation/deflation may effectively mitigate this problem. METHODS: A lethal abdominal vascular injury was created in 28 swine. Animals were randomized to controls (n=7), 60min full REBOA (FR, n=5), time-based intermittent REBOA (iRT, n=7), and pressure-based REBOA (iRP, n=9). Intermittent groups had an initial inflation for 15min, followed by 10min inflation: 3min deflation cycles (iRT) or an inflate/deflate schedule based on blood pressure (MAP)<40mmHg (iRP). Experiments were concluded after 120min or death (MAP<20mmHg). RESULTS: Intermittent REBOA animals all survived to 120min versus 15min for controls and 63min for FR(p<0.001). After 60min, FR animals were more hypotensive(MAP 20mmHg vs 80mmHg(iRP) and 100mmHg(iRT), p<0.001), had lower cardiac output(1.06mL/min vs 5.1L/min(iRP) and 8.2L/min(iRT), p<0.001), higher lactate(12.5mg/dL vs 8.5mg/dL(iRP), p=0.02), and decreased clot firmness on ROTEM than iRP/T(64mm vs 69mm(iRP) and 69mm(iRT), p=0.04). Acidosis was worse in iRT versus iRP at 120min (pH 7.28 vs 7.12, p=0.02), improved lactate (11.9mg/dL vs 16.3mg/dL, p=0.04), and decreased whole blood resuscitation (452cc vs 646cc, p=0.05). Blood loss (clot weight) was higher in controls (2.0kg) versus iRT and iRP(1.16kg and 1.23kg, p<0.01) and not different from FR(0.87kg, p=0.10). CONCLUSION: Intermittent REBOA can maintain supraceliac hemorrhage control while decreasing distal ischemia in a swine model. Prolonged survival times, decreased acidosis, and lower resuscitation requirements indicate that this technique could potentially extend Zone 1 REBOA deployment times. Schedules based on MAP may be superior to time-based regimens. LEVEL OF EVIDENCE: Not applicable as an animal study. STUDY DESIGN: Original article. PMID- 29787558 TI - A new weighted injury severity scoring system: Better predictive power for pediatric trauma mortality. AB - BACKGROUND: An accurate injury severity measurement is essential for the evaluation of pediatric trauma care and outcome research. The traditional Injury Severity Score (ISS) does not consider the differential risks of the Abbreviated Injury Scale (AIS) from different body regions nor is it pediatric specific. The objective of this study was to develop a weighted ISS (wISS) system for pediatric blunt trauma patients with better predictive power than ISS. METHODS: Based on the association between mortality and AIS from each of the six ISS body regions, we generated different weights for the component AIS scores used in the calculation of ISS. The weights and wISS were generated using the National Trauma Data Bank. The Nationwide Emergency Department Sample (NEDS) was used to validate our main results. Pediatric blunt trauma patients younger than 16 years were included, and mortality was the outcome. Discrimination (areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, concordance) and calibration (Hosmer-Lemeshow statistic) were compared between the wISS and ISS. RESULTS: The areas under the receiver operating characteristic curves from the wISS and ISS are 0.88 versus 0.86 in ISS of 1 to 74 and 0.77 versus 0.64 in ISS of 25 to 74 (p < 0.0001). The wISS showed higher specificity, positive predictive value, negative predictive value, and concordance when they were compared at similar levels of sensitivity. The wISS had better calibration (smaller Hosmer-Lemeshow statistic) than the ISS (11.6 vs. 19.7 for ISS = 1-74 and 10.9 vs. 12.6 for ISS = 25-74). The wISS showed even better discrimination with the Nationwide Emergency Department Sample. CONCLUSION: By weighting the AIS from different body regions, the wISS had significantly better predictive power for mortality than the ISS, especially in critically injured children. LEVEL OF EVIDENCE AND STUDY TYPE: Prognostic/epidemiological, level IV. PMID- 29787559 TI - Peptidoglycan Suppresses Phagocytic Activities and Apoptosis of Macrophages in Colonic Mucosa Tissues of Crohn's Disease Patients and In Vitro. AB - BACKGROUND Rac1 signaling plays a crucial role in controlling macrophage functions in CD. Peptidoglycan triggers several intracellular signaling pathways, including activation of Rac1, to regulate the function of macrophage. Suppressed Rac1 signaling in non-inflamed colonic mucosa of Crohn's disease patients has been shown to correlate with increased innate immunity. MATERIAL AND METHODS We examined the effect of peptidoglycan on Rac1 signaling in macrophages and mucosal tissue samples collected from 10 patients with active Crohn's disease and further investigated the effects of peptidoglycan on apoptosis and phagocytic activities of macrophages in vitro. RESULTS Macrophage infiltration and Rac1 signaling was increased in inflamed mucosal tissues of Crohn's disease patients. Immunoblotting assays revealed that peptidoglycan dose- and time-dependently increased the expression of Rac1-GTP, phosphorylated VAV1, and phosphorylated PAK1in RAW264.7 macrophages, which, however, was attenuated by 6-thioguanine. Peptidoglycan also dose-dependently inhibited phagocytic activities of human peripheral blood monocytic cells (PBMCs), which were partially abated by 6-thioguanine or NSC23766. Flow cytometry showed that peptidoglycan (3 MUg/mL) decreased the proportion of apoptotic human PBMCs versus controls. The addition of 6 thioguanine or NSC3766 to peptidoglycan led to a sharper rise in the proportion of apoptotic human PBMCs than 6-thioguanine or NSC3766 alone. CONCLUSIONS Our findings suggest that Rac1 signaling is a common molecular target shared by peptidoglycan and immunosuppressive treatment in intestinal macrophages. Inhibiting Rac1 activation may be crucial for optimizing macrophage immunity for treatment of Crohn's disease. PMID- 29787560 TI - Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study. AB - BACKGROUND: Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays. OBJECTIVE: The aim of this study was to define pregnancy related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age. STUDY DESIGN: A retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient. RESULTS: A total of 11,415 patients were included. Mean PLR and NLR values were 136.3+/-44.3, 2.6+/-1, respectively during the first trimester, 144.6+/-47.1, 4.0+/-1.4 respectively during the second trimester and 118.1+/-42.0, 3.5+/-1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively). CONCLUSIONS: In our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy. PMID- 29787562 TI - A thirty year, fine-scale, characterization of area burned in Canadian forests shows evidence of regionally increasing trends in the last decade. AB - Fire as a dominant disturbance has profound implications on the terrestrial carbon cycle. We present the first ever multi-decadal, spatially-explicit, 30 meter assessment of fire regimes across the forested ecoregions of Canada at an annual time-step. From 1985 to 2015, 51 Mha burned, impacting over 6.5% of forested ecosystems. Mean annual area burned was 1,651,818 ha and varied markedly (sigma = 1,116,119), with 25% of the total area burned occurring in three years: 1989, 1995, and 2015. Boreal forest types contained 98% of the total area burned, with the conifer-dominated Boreal Shield containing one-third of all burned area. While results confirm no significant national trend in burned area for the period of 1985 to 2015, a significant national increasing trend (alpha = 0.05) of 11% per year was evident for the past decade (2006 to 2015). Regionally, a significant increasing trend in total burned area from 1985 to 2015 was observed in the Montane Cordillera (2.4% increase per year), while the Taiga Plains and Taiga Shield West displayed significant increasing trends from 2006 to 2015 (26.1% and 12.7% increases per year, respectively). The Atlantic Maritime, which had the lowest burned area of all ecozones (0.01% burned per year), was the only ecozone to display a significant negative trend (2.4% decrease per year) from 1985 to 2015. Given the century-long fire return intervals in many of these ecozones, and large annual variability in burned area, short-term trends need to be interpreted with caution. Additional interpretive cautions are related to year used for trend initiation and the nature and extents of spatial regionalizations used for summarizing findings. The results of our analysis provide a baseline for monitoring future national and regional trends in burned area and offer spatially and temporally detailed insights to inform science, policy, and management. PMID- 29787561 TI - Interplay of strain and race/ethnicity in the innate immune response to M. tuberculosis. AB - BACKGROUND: The roles of host and pathogen factors in determining innate immune responses to M. tuberculosis are not fully understood. In this study, we examined host macrophage immune responses of 3 race/ethnic groups to 3 genetically and geographically diverse M. tuberculosis lineages. METHODS: Monocyte-derived macrophages from healthy Filipinos, Chinese and non-Hispanic White study participants (approximately 45 individuals/group) were challenged with M. tuberculosis whole cell lysates of clinical strains Beijing HN878 (lineage 2), Manila T31 (lineage 1), CDC1551 (lineage 4), the reference strain H37Rv (lineage 4), as well as with Toll-like receptor 2 agonist lipoteichoic acid (TLR2/LTA) and TLR4 agonist lipopolysaccharide (TLR4/LPS). Following overnight incubation, multiplex assays for nine cytokines: IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12p70, IFNgamma, TNFalpha, and GM-CSF, were batch applied to supernatants. RESULTS: Filipino macrophages produced less IL-1, IL-6, and more IL-8, compared to macrophages from Chinese and Whites. Race/ethnicity had only subtle effects or no impact on the levels of IL-10, IL-12p70, TNFalpha and GM-CSF. In response to the Toll-like receptor 2 agonist lipoteichoic acid (TLR2/LTA), Filipino macrophages again had lower IL-1 and IL-6 responses and a higher IL-8 response, compared to Chinese and Whites. The TLR2/LTA-stimulated Filipino macrophages also produced lower amounts of IL-10, TNFalpha and GM-CSF. Race/ethnicity had no impact on IL 12p70 levels released in response to TLR2/LTA. The responses to TLR4 agonist lipopolysaccharide (TLR4/LPS) were similar to the TLR2/LTA responses, for IL-1, IL-6, IL-8, and IL-10. However, TLR4/LPS triggered the release of less IL-12p70 from Filipino macrophages, and less TNFalpha from White macrophages. CONCLUSIONS: Both host race/ethnicity and pathogen strain influence the innate immune response. Such variation may have implications for the development of new tools across TB therapeutics, immunodiagnostics and vaccines. PMID- 29787563 TI - Graph complexity analysis identifies an ETV5 tumor-specific network in human and murine low-grade glioma. AB - Conventional differential expression analyses have been successfully employed to identify genes whose levels change across experimental conditions. One limitation of this approach is the inability to discover central regulators that control gene expression networks. In addition, while methods for identifying central nodes in a network are widely implemented, the bioinformatics validation process and the theoretical error estimates that reflect the uncertainty in each step of the analysis are rarely considered. Using the betweenness centrality measure, we identified Etv5 as a potential tissue-level regulator in murine neurofibromatosis type 1 (Nf1) low-grade brain tumors (optic gliomas). As such, the expression of Etv5 and Etv5 target genes were increased in multiple independently-generated mouse optic glioma models relative to non-neoplastic (normal healthy) optic nerves, as well as in the cognate human tumors (pilocytic astrocytoma) relative to normal human brain. Importantly, differential Etv5 and Etv5 network expression was not directly the result of Nf1 gene dysfunction in specific cell types, but rather reflects a property of the tumor as an aggregate tissue. Moreover, this differential Etv5 expression was independently validated at the RNA and protein levels. Taken together, the combined use of network analysis, differential RNA expression findings, and experimental validation highlights the potential of the computational network approach to provide new insights into tumor biology. PMID- 29787565 TI - Expression, purification, and inhibition profile of dihydrofolate reductase from the filarial nematode Wuchereria bancrofti. AB - Filariasis is a tropical disease caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. Known inhibitors of dihydrofolate reductase (DHFR) have been previously shown to kill Brugia malayi nematodes and to inhibit Brugia malayi DHFR (BmDHFR) at nanomolar concentrations. These data suggest that BmDHFR is a potential target for the treatment of filariasis. Here, protocols for cloning, expression and purification of Wuchereria bancrofti DHFR (WbDHFR) were developed. The Uniprot entry J9F199-1 predicts a 172 amino acid protein for WbDHFR but alignment of this sequence to the previously described BmDHFR shows that this WbDHFR sequence lacks a crucial, conserved 13 amino acid loop. The presence of the loop in WbDHFR is supported by a noncanonical splicing event and the loop sequence was therefore included in the gene design. Subsequently, the KM for dihydrofolate (3.7 +/- 2 MUM), kcat (7.4 +/- 0.6 s-1), and pH dependence of activity were determined. IC50 values of methotrexate, trimethoprim, pyrimethamine, raltitrexed, aminopterin, (-)-epicatechin gallate, (-) epicatechin, and vitexin were measured for WbDHFR and BmDHFR. Methotrexate and structurally related aminopterin were found to be effective inhibitors of WbDHFR, with an KI of 1.2 +/- 0.2 nM and 2.1 +/- 0.5 nM, respectively, suggesting that repurposing of known antifolate compound may be an effective strategy to treating filariasis. Most compounds showed similar inhibition profiles toward both enzymes, suggesting that the two enzymes have important similarities in their active site environments and can be targeted with the same compound, once a successful inhibitor is identified. PMID- 29787564 TI - Microbial micropatches within microbial hotspots. AB - The spatial distributions of organism abundance and diversity are often heterogeneous. This includes the sub-centimetre distributions of microbes, which have 'hotspots' of high abundance, and 'coldspots' of low abundance. Previously we showed that 300 MUl abundance hotspots, coldspots and background regions were distinct at all taxonomic levels. Here we build on these results by showing taxonomic micropatches within these 300 MUl microscale hotspots, coldspots and background regions at the 1 MUl scale. This heterogeneity among 1 MUl subsamples was driven by heightened abundance of specific genera. The micropatches were most pronounced within hotspots. Micropatches were dominated by Pseudomonas, Bacteroides, Parasporobacterium and Lachnospiraceae incertae sedis, with Pseudomonas and Bacteroides being responsible for a shift in the most dominant genera in individual hotspot subsamples, representing up to 80.6% and 47.3% average abundance, respectively. The presence of these micropatches implies the ability these groups have to create, establish themselves in, or exploit heterogeneous microenvironments. These genera are often particle-associated, from which we infer that these micropatches are evidence for sub-millimetre aggregates and the aquatic polymer matrix. These findings support the emerging paradigm that the microscale distributions of planktonic microbes are numerically and taxonomically heterogeneous at scales of millimetres and less. We show that microscale microbial hotspots have internal structure within which specific local nutrient exchanges and cellular interactions might occur. PMID- 29787566 TI - Influence of learning strategy on response time during complex value-based learning and choice. AB - Measurements of response time (RT) have long been used to infer neural processes underlying various cognitive functions such as working memory, attention, and decision making. However, it is currently unknown if RT is also informative about various stages of value-based choice, particularly how reward values are constructed. To investigate these questions, we analyzed the pattern of RT during a set of multi-dimensional learning and decision-making tasks that can prompt subjects to adopt different learning strategies. In our experiments, subjects could use reward feedback to directly learn reward values associated with possible choice options (object-based learning). Alternatively, they could learn reward values of options' features (e.g. color, shape) and combine these values to estimate reward values for individual options (feature-based learning). We found that RT was slower when the difference between subjects' estimates of reward probabilities for the two alternative objects on a given trial was smaller. Moreover, RT was overall faster when the preceding trial was rewarded or when the previously selected object was present. These effects, however, were mediated by an interaction between these factors such that subjects were faster when the previously selected object was present rather than absent but only after unrewarded trials. Finally, RT reflected the learning strategy (i.e. object-based or feature-based approach) adopted by the subject on a trial-by-trial basis, indicating an overall faster construction of reward value and/or value comparison during object-based learning. Altogether, these results demonstrate that the pattern of RT can be informative about how reward values are learned and constructed during complex value-based learning and decision making. PMID- 29787568 TI - Using Discursis to enhance the qualitative analysis of hospital pharmacist patient interactions. AB - INTRODUCTION: Pharmacist-patient communication during medication counselling has been successfully investigated using Communication Accommodation Theory (CAT). Communication researchers in other healthcare professions have utilised Discursis software as an adjunct to their manual qualitative analysis processes. Discursis provides a visual, chronological representation of communication exchanges and identifies patterns of interactant engagement. AIM: The aim of this study was to describe how Discursis software was used to enhance previously conducted qualitative analysis of pharmacist-patient interactions (by visualising pharmacist-patient speech patterns, episodes of engagement, and identifying CAT strategies employed by pharmacists within these episodes). METHODS: Visual plots from 48 transcribed audio recordings of pharmacist-patient exchanges were generated by Discursis. Representative plots were selected to show moderate-high and low- level speaker engagement. Details of engagement were investigated for pharmacist application of CAT strategies (approximation, interpretability, discourse management, emotional expression, and interpersonal control). RESULTS: Discursis plots allowed for identification of distinct patterns occurring within pharmacist-patient exchanges. Moderate-high pharmacist-patient engagement was characterised by multiple off-diagonal squares while alternating single coloured squares depicted low engagement. Engagement episodes were associated with multiple CAT strategies such as discourse management (open-ended questions). Patterns reflecting pharmacist or patient speaker dominance were dependant on clinical setting. DISCUSSION AND CONCLUSIONS: Discursis analysis of pharmacist patient interactions, a novel application of the technology in health communication, was found to be an effective visualisation tool to pin-point episodes for CAT analysis. Discursis has numerous practical and theoretical applications for future health communication research and training. Researchers can use the software to support qualitative analysis where large data sets can be quickly reviewed to identify key areas for concentrated analysis. Because Discursis plots are easily generated from audio recorded transcripts, they are conducive as teaching tools for both students and practitioners to assess and develop their communication skills. PMID- 29787567 TI - Automated method to differentiate between native and mirror protein models obtained from contact maps. AB - Mirror protein structures are often considered as artifacts in modeling protein structures. However, they may soon become a new branch of biochemistry. Moreover, methods of protein structure reconstruction, based on their residue-residue contact maps, need methodology to differentiate between models of native and mirror orientation, especially regarding the reconstructed backbones. We analyzed 130 500 structural protein models obtained from contact maps of 1 305 SCOP domains belonging to all 7 structural classes. On average, the same numbers of native and mirror models were obtained among 100 models generated for each domain. Since their structural features are often not sufficient for differentiating between the two types of model orientations, we proposed to apply various energy terms (ETs) from PyRosetta to separate native and mirror models. To automate the procedure for differentiating these models, the k-means clustering algorithm was applied. Using total energy did not allow to obtain appropriate clusters-the accuracy of the clustering for class A (all helices) was no more than 0.52. Therefore, we tested a series of different k-means clusterings based on various combinations of ETs. Finally, applying two most differentiating ETs for each class allowed to obtain satisfying results. To unify the method for differentiating between native and mirror models, independent of their structural class, the two best ETs for each class were considered. Finally, the k-means clustering algorithm used three common ETs: probability of amino acid assuming certain values of dihedral angles Phi and Psi, Ramachandran preferences and Coulomb interactions. The accuracies of clustering with these ETs were in the range between 0.68 and 0.76, with sensitivity and selectivity in the range between 0.68 and 0.87, depending on the structural class. The method can be applied to all fully-automated tools for protein structure reconstruction based on contact maps, especially those analyzing big sets of models. PMID- 29787570 TI - Adjuvant chemotherapy-Radiotherapy-Chemotherapy sandwich protocol in resectable soft tissue sarcoma: An updated single-center analysis of 104 cases. AB - Adjuvant therapy of local soft tissue sarcomas (STS) after wide surgical excision still is a topic under controversial scientific debate. In this single center report we have offered an adjuvant "sandwich" therapy protocol consisting of 4 cycles of doxorubicin (75 mg/m2 i.v. over 1 h on day 1) followed by ifosfamide (5 g/m2 i.v. over 24 h starting on day 1) and local radiotherapy scheduled between chemotherapy cycles 2 and 3 to 104 consecutive patients after wide surgical excision (R0) of histologically proven high-grade STS. After a mean follow-up of 39 months (range 5-194 months) relapse free survival (RFS) at 2 and 5 years was 68.1% (95% CI, 58.5-77.7%) and 61.2% (95% CI, 50.4-71.6%). When analyzing the 82 STS cases of the extremities only 2- and 5-year RFS was 74.0% (95% CI, 64.0 84.0%) and 65.3% (95% CI, 53.7-76.9%). By intent-to-treat analysis, the overall survival (OS) at 2 years was 87.3% (95% CI, 80.5-94.1%) and 75.6% (95% CI, 65.2 86.0%) at 5 years, while OS for STS of the extremities only cohort was 90.5% (95% CI, 83.7-97.3%) and 79.0% (95% CI, 68.4-89.6%), respectively. Tolerability of the treatment was good. This analysis demonstrates the feasibility of adjuvant chemoradiotherapy and reflects the results of the long lasting intensive multidisciplinary team approach at our "high-volume" sarcoma center. The long term survival in our patients is among the highest reported and the low local and distant recurrence rate in high-risk STS is at least comparable to the published data. PMID- 29787571 TI - RNAi screening of subtracted transcriptomes reveals tumor suppression by taurine activated GABAA receptors involved in volume regulation. AB - To identify coding and non-coding suppressor genes of anchorage-independent proliferation by efficient loss-of-function screening, we have developed a method for enzymatic production of low complexity shRNA libraries from subtracted transcriptomes. We produced and screened two LEGO (Low-complexity by Enrichment for Genes shut Off) shRNA libraries that were enriched for shRNA vectors targeting coding and non-coding polyadenylated transcripts that were reduced in transformed Mouse Embryonic Fibroblasts (MEFs). The LEGO shRNA libraries included ~25 shRNA vectors per transcript which limited off-target artifacts. Our method identified 79 coding and non-coding suppressor transcripts. We found that taurine responsive GABAA receptor subunits, including GABRA5 and GABRB3, were induced during the arrest of non-transformed anchor-deprived MEFs and prevented anchorless proliferation. We show that taurine activates chloride currents through GABAA receptors on MEFs, causing seclusion of cell volume in large membrane protrusions. Volume seclusion from cells by taurine correlated with reduced proliferation and, conversely, suppression of this pathway allowed anchorage-independent proliferation. In human cholangiocarcinomas, we found that several proteins involved in taurine signaling via GABAA receptors were repressed. Low GABRA5 expression typified hyperproliferative tumors, and loss of taurine signaling correlated with reduced patient survival, suggesting this tumor suppressive mechanism operates in vivo. PMID- 29787572 TI - TDP-43 causes neurotoxicity and cytoskeletal dysfunction in primary cortical neurons. AB - TDP-43-mediated proteinopathy is a key factor in the pathology of amyotrophic lateral sclerosis (ALS). A potential underlying mechanism is dysregulation of the cytoskeleton. Here we investigate the effects of expressing TDP-43 wild-type and M337V and Q331K mutant isoforms on cytoskeletal integrity and function, using rat cortical neurons in vitro. We find that TDP-43 protein becomes mislocalised in axons over 24-72 hours in culture, with protein aggregation occurring at later timepoints (144 hours). Quantitation of cell viability showed toxicity of both wild-type and mutant constructs which increased over time, especially of the Q331K mutant isoform. Analysis of the effects of TDP-43 on axonal integrity showed that TDP-43-transfected neurons had shorter axons than control cells, and that growth cone sizes were smaller. Axonal transport dynamics were also impaired by transfection with TDP-43 constructs. Taken together these data show that TDP 43 mislocalisation into axons precedes cell death in cortical neurons, and that cytoskeletal structure and function is impaired by expression of either TDP-43 wild-type or mutant constructs in vitro. These data suggest that dysregulation of cytoskeletal and neuronal integrity is an important mechanism for TDP-43-mediated proteinopathy. PMID- 29787569 TI - Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study. AB - INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP 1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (rho = 0.57, P = 0.03), CDUS (rho = 0.53, P = 0.04) and bone marrow oedema (rho = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit. CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects. PMID- 29787573 TI - Male resource defense mating system in primates? An experimental test in wild capuchin monkeys. AB - Ecological models of mating systems provide a theoretical framework to predict the effect of the defendability of both breeding resources and mating partners on mating patterns. In resource-based mating systems, male control over breeding resources is tightly linked to female mating preference. To date, few field studies have experimentally investigated the relationship between male resource control and female mating preference in mammals due to difficulties in manipulating ecological factors (e.g., food contestability). We tested the within group male resource defense hypothesis experimentally in a wild population of black capuchin monkeys (Sapajus nigritus) in Iguazu National Park, Argentina. Sapajus spp. represent an ideal study model as, in contrast to most primates, they have been previously argued to be characterized by female mate choice and a resource-based mating system in which within-group resource monopolization by high-ranking males drives female mating preference for those males. Here, we examined whether females (N = 12) showed a weaker preference for alpha males during mating seasons in which food distribution was experimentally manipulated to be less defendable relative to those in which it was highly defendable. Results did not support the within-group male resource defense hypothesis, as female sexual preferences for alpha males did not vary based on food defendability. We discuss possible reasons for our results, including the possibility of other direct and indirect benefits females receive in exercising mate choice, the potential lack of tolerance over food directed towards females by alpha males, and phylogenetic constraints. PMID- 29787574 TI - Child morbidity and mortality associated with alternative policy responses to the economic crisis in Brazil: A nationwide microsimulation study. AB - BACKGROUND: Since 2015, a major economic crisis in Brazil has led to increasing poverty and the implementation of long-term fiscal austerity measures that will substantially reduce expenditure on social welfare programmes as a percentage of the country's GDP over the next 20 years. The Bolsa Familia Programme (BFP)-one of the largest conditional cash transfer programmes in the world-and the nationwide primary healthcare strategy (Estrategia Saude da Familia [ESF]) are affected by fiscal austerity, despite being among the policy interventions with the strongest estimated impact on child mortality in the country. We investigated how reduced coverage of the BFP and ESF-compared to an alternative scenario where the level of social protection under these programmes is maintained-may affect the under-five mortality rate (U5MR) and socioeconomic inequalities in child health in the country until 2030, the end date of the Sustainable Development Goals. METHODS AND FINDINGS: We developed and validated a microsimulation model, creating a synthetic cohort of all 5,507 Brazilian municipalities for the period 2017-2030. This model was based on the longitudinal dataset and effect estimates from a previously published study that evaluated the effects of poverty, the BFP, and the ESF on child health. We forecast the economic crisis and the effect of reductions in BFP and ESF coverage due to current fiscal austerity on the U5MR, and compared this scenario with a scenario where these programmes maintain the levels of social protection by increasing or decreasing with the size of Brazil's vulnerable populations (policy response scenarios). We used fixed effects multivariate regression models including BFP and ESF coverage and accounting for secular trends, demographic and socioeconomic changes, and programme duration effects. With the maintenance of the levels of social protection provided by the BFP and ESF, in the most likely economic crisis scenario the U5MR is expected to be 8.57% (95% CI: 6.88%-10.24%) lower in 2030 than under fiscal austerity-a cumulative 19,732 (95% CI: 10,207-29,285) averted under-five deaths between 2017 and 2030. U5MRs from diarrhoea, malnutrition, and lower respiratory tract infections are projected to be 39.3% (95% CI: 36.9%-41.8%), 35.8% (95% CI: 31.5% 39.9%), and 8.5% (95% CI: 4.1%-12.0%) lower, respectively, in 2030 under the maintenance of BFP and ESF coverage, with 123,549 fewer under-five hospitalisations from all causes over the study period. Reduced coverage of the BFP and ESF will also disproportionately affect U5MR in the most vulnerable areas, with the U5MR in the poorest quintile of municipalities expected to be 11.0% (95% CI: 8.0%-13.8%) lower in 2030 under the maintenance of BFP and ESF levels of social protection than under fiscal austerity, compared to no difference in the richest quintile. Declines in health inequalities over the last decade will also stop under a fiscal austerity scenario: the U5MR concentration index is expected to remain stable over the period 2017-2030, compared to a 13.3% (95% CI: 5.6%-21.8%) reduction under the maintenance of BFP and ESF levels of protection. Limitations of our analysis are the ecological nature of the study, uncertainty around future macroeconomic scenarios, and potential changes in other factors affecting child health. A wide range of sensitivity analyses were conducted to minimise these limitations. CONCLUSIONS: The implementation of fiscal austerity measures in Brazil can be responsible for substantively higher childhood morbidity and mortality than expected under maintenance of social protection-threatening attainment of Sustainable Development Goals for child health and reducing inequality. PMID- 29787575 TI - Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms. AB - BACKGROUND: Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria. METHODS: The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0-4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days. RESULTS: The average age was 65 years (range 47-83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4-11). The average time from wake-up to IV tPA was 205 minutes (range 114-270). The average time from last known well to IV tPA was 580 minutes (range 353-876). The median mRS at 90 days was 1 (range 0-5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging. CONCLUSIONS: Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01643902. PMID- 29787576 TI - Flotillin proteins recruit sphingosine to membranes and maintain cellular sphingosine-1-phosphate levels. AB - Sphingosine-1-phosphate (S1P) is an important lipid signalling molecule. S1P is produced via intracellular phosphorylation of sphingosine (Sph). As a lipid with a single fatty alkyl chain, Sph may diffuse rapidly between cellular membranes and through the aqueous phase. Here, we show that the absence of microdomains generated by multimeric assemblies of flotillin proteins results in reduced S1P levels. Cellular phenotypes of flotillin knockout mice, including changes in histone acetylation and expression of Isg15, are recapitulated when S1P synthesis is perturbed. Flotillins bind to Sph in vitro and increase recruitment of Sph to membranes in cells. Ectopic re-localisation of flotillins within the cell causes concomitant redistribution of Sph. The data suggest that flotillins may directly or indirectly regulate cellular sphingolipid distribution and signalling. PMID- 29787577 TI - Analysis of microRNAs in familial Mediterranean fever. AB - OBJECTIVES: Although Familial Mediterranean fever (FMF) is categorized as autosomal recessive, frequent exceptions to this model exist and therefore we aimed to search epigenetic modifications in this disease. METHODS: Ten M694V homozygous FMF patients (the most severe phenotype) were recruited for this study. Patients with inflammatory flare were excluded. Total RNA was extracted from peripheral blood, and microRNA expression profiled using NanoString nCounter technology. These patients were compared to 10 healthy age- and sex-matched controls. RESULTS: Seven hundred nighty-eight mature human miRNAs were probed, 103 of which had expression levels above the negative control probes. Seven miRNAs showed significant differences in expression in samples from FMF patients compared to healthy controls: four miRNAs were upregulated (miR-144-3p, miR-21 5p, miR-4454, and miR-451a), and three were downregulated (miR-107, let-7d-5p, and miR-148b-3p). CONCLUSION: In this pilot study, we identified epigenetic modifications in clinically quiescent FMF patients. More studies are required for exploration of their contribution to FMF pathogenesis and their potential role as clinical biomarkers. PMID- 29787579 TI - Conformity of package inserts information to regulatory requirements among selected branded and generic medicinal products circulating on the East African market. AB - BACKGROUND: Availability of correct and adequate information about medicines is an important aspect in ensuring rational use of medicines and hence facilitating safety and expected efficacy of medicines during therapy. Package inserts have proven to be a good source of information to the prescribers and patients whereby they have been useful in highlighting important information pertaining proper use and handling of the medicines. The present study was aimed at establishing the extent to which package inserts of medicines circulating on the markets of the East African Community (EAC) Partner States conform to medicines information requirements as established in the harmonized guidelines as well as national guidelines. METHODS: A total of 99 package inserts from six (6) types of medicines namely Albendazole, Artemether/Lumefantrine (ALu), Ciprofloxacin, Paracetamol, Amoxicillin and Metronidazole were purposefully collected from three EAC Partner States: Kenya, Tanzania and Uganda. The medicines were selected based on their indications as first line treatments, high rates of utilization within the medicines supply system and their positions in treatment of diseases of public importance across EAC Partner States. The inserts were evaluated on the availability of information regarding fifteen (15) parameters as extracted from the EAC harmonized guidelines for registration of medicines. Moreover, comparisons were made between the percentage conformity of the branded versus generic products, markets from which the samples were collected, origin of the manufacturer and type of medicine. RESULTS: Majority (93.9-100%) of the medicines' package inserts highly conformed to the inclusion of the information regarding the description and composition of the medications, indications, dosage and methods of administration, warnings and precautions, contraindications and storage conditions. However, the information on handling and disposal, container package description, excipients used, clinical pharmacology of the medicines, and directions regarding overdose ranked the least in conformance with conformity ranging from 13.1-52.5%. The parameter with the lowest observed percentage conformity among the branded products scored 50% as compared to 10.8% among the generic products. Moreover, there was no significant difference (P<0.05) in the percentage conformity of the package inserts collected from each of the three Partner States as compared to the average from studied medicines. A generally good conformity was observed among medicines manufactured by European based manufacturers as compared to those based in Asia and EAC Partner States. In addition, PIs of Albendazole, Ciprofloxacin, Amoxicillin and Artemether/Lumefantrine did show overall high conformity across most of the product information requirements. CONCLUSION: Our study revealed the existence of a significant number of medicinal products circulating on the markets of EAC Partner States without necessary compliance with all product information requirements. We therefore recommend that NMRAs ensure thorough pre-market assessment of product information as well as strengthening their post marketing surveillance to ensure that medicines circulating on the market comply to medicines information requirements at all times. Emphasis should also be given to manufacturers on the importance of inclusion of appropriate and adequate product information for the safety of patients, including advocating for inclusion of patient-friendly and easy to understand medicines information. PMID- 29787578 TI - mTh1 driven expression of hTDP-43 results in typical ALS/FTLD neuropathological symptoms. AB - Transgenic mouse models are indispensable tools to mimic human diseases and analyze the effectiveness of related new drugs. For a long time amyotrophic lateral sclerosis (ALS) research depended on only a few mouse models that exhibit a very strong and early phenotype, e.g. SOD1 mice, resulting in a short treatment time window. By now, several models are available that need to be characterized to highlight characteristics of each model. Here we further characterized the mThy1-hTDP-43 transgenic mouse model TAR6/6 that overexpresses wild type human TARDBP, also called TDP-43, under control of the neuronal Thy-1 promoter presented by Wils and colleagues, 2010, by using biochemical, histological and behavioral readouts. Our results show that TAR6/6 mice exhibit a strong TDP-43 expression in the hippocampus, spinal cord, hypothalamus and medulla oblongata. Apart from prominent protein expression in the nucleus, TDP-43 protein was found at lower levels in the cytosol of transgenic mice. Additionally, we detected insoluble TDP-43 in the cortex, motoneuron loss, and increased neuroinflammation in the central nervous system of TAR6/6 animals. Behavioral analyses revealed early motor deficits in the clasping- and wire suspension test as well as decreased anxiety in the elevated plus maze. Further motor tests showed differences at later time points compared to non-transgenic littermates, thus allowing the observation of onset and severity of such deficits. Together, TAR6/6 mice are a valuable tool to test new ALS/FTLD drugs that target TDP-43 expression and insolubility, neuroinflammation, motoneuron loss or other TDP-43 related downstream signaling pathways since these mice exhibit a later pathology as previously used ALS/FTLD mouse models. PMID- 29787580 TI - Risk behaviors and HIV care continuum outcomes among criminal justice-involved HIV-infected transgender women and cisgender men: Data from the Seek, Test, Treat, and Retain Harmonization Initiative. AB - BACKGROUND: Transgender persons are highly victimized, marginalized, disproportionately experience incarceration, and have alarmingly increased rates of HIV infection compared to cis-gender persons. Few studies have examined the HIV care continuum outcomes among transgender women (TW), particularly TW who are involved with the criminal justice (CJ) system. METHODS: To improve our understanding of HIV care continuum outcomes and risk behaviors among HIV infected TW who are involved with the CJ system, we analyzed data from the National Institute on Drug Abuse-supported Seek, Test, Treat, Retain (STTR) Data Harmonization Initiative. Baseline data were pooled and analyzed from three U.S. STTR studies to examine HIV risk and care continuum indicators among CJ-involved HIV-infected TW compared to cisgender men (CM), matched on age (within 5 years) and study at a ratio of 1:5. RESULTS: Eighty-eight TW and 440 CM were included in the study. Among matched participants, TW were more likely to report crack and cocaine use compared to CM (40%,16% respectively, p<0.001); both TW and CM reported high rates of condomless sex (58%, 64%, respectively); TW were more likely than CM to have more than one sexual partner (OR = 2.9, 95% CI: 1.6, 5.2; p<0.001) and have engaged in exchange sex (OR = 3.9, 95% CI: 2.3, 6.6; p<0.001). There were no significant differences between TW and CM in the percentage currently taking ART (52%, 49%, respectively), the mean percent adherence to ART (77% for both groups), and the proportion who achieved viral suppression (61%, 58%, respectively). CONCLUSIONS: HIV-infected CJ-involved TW and CM had similar use of ART and viral suppression but TW were more likely than matched CM to engage in exchange sex, have multiple sexual partners, and use crack/cocaine. TW and CM had similarly high rates of condomless sex and use of other drugs. TW require tailored risk reduction interventions, however both CJ-involved TW and CM require focused attention to reduce HIV risk and improve HIV continuum of care outcomes. PMID- 29787581 TI - Autologous and not allogeneic adipose-derived stem cells improve acute burn wound healing. AB - Adipose-derived stem cells (ADSCs) transplant has been reported to be a potential treatment for burn wounds. However, the effects of autogenicity and allogenicity of ADSCs on burn wound healing have not been investigated and the method for using ADSCs still needs to be established. This study compared the healing effects of autologous and allogenic ADSCs and determined an optimal method of using ADSCs to treat acute burn wounds. Experiments were performed in 20 male Wistar rats (weight, 176-250 g; age, 6-7 weeks). Two identical full-thickness burn wounds (radius, 4 mm) were created in each rat. ADSCs harvested from inguinal area and characterized by their high multipotency were injected into burn wounds in the original donor rats (autologous ADSCs group) or in other rats (allogenic ADSCs group). The injection site was either the wound center or the four corners 0.5 cm from the wound edge. The reduction of burn surface areas in the two experimental groups and in control group were evaluated with Image J software for 15 days post-wounding to determine the wound healing rates. Wound healing was significantly faster in the autologous ADSCs group compared to both the allogenic ADSCs group (p<0.05) and control group (p<0.05). Wound healing in the allogenic ADSC group did not significantly differ from that in control group. Notably, ADSC injections 0.5cm from the wound edge showed significantly improved healing compared to ADSCs injections in the wound center (p<0.05). This study demonstrated the therapeutic efficacy of ADSCs in treating acute burn wounds in rats. However, only autologous ADSCs improved healing in acute burn wounds; allogenic ADSCs did not. This study further determined a superior location of using ADSCs injections to treat burn wounds including the injection site. Future studies will replicate the experiment in a larger and long-term scale burn wounds in higher mammalian models to facilitate ADSCs therapy in burn wound clinical practice. PMID- 29787582 TI - Determination of red blood cell deformability using centrifugal force in a three dimensional-printed mini-disk (3D-PMD). AB - Measuring red blood cell (RBC) deformability has become important for clinical disease diagnostics. Various methods for measuring RBC deformability have been developed; however, they require costly and large instruments, long measuring time, and skilled personnel. In this study, we present a three-dimensional printed mini-disk (3D-PMD) for measuring RBC deformability to overcome the previous limitations. For a miniaturized and low-cost setup, the 3D-PMD was fabricated by a 3D printing technique, which had not yet been used for fabricating a lab-on-a-compact disk (LOCD). Using a 3D printing technique, a multi-layered fluidic channel on the mini CD could be fabricated easily. During rotation by a spinning motor, the difference of the length of compressed RBCs in the fluidic channel was measured and analysed as compressibility indices (CIs) of normal and glutaraldehyde-treated hardened RBCs. The rotation speed and time were decided as 3000 rpm and 30 min, respectively, at which the difference of CI values between normal and hardened RBCs was largest (CInormal-CIhardened = 0.195). PMID- 29787583 TI - Gender associated muscle-tendon adaptations to resistance training. AB - PURPOSE: To compare the relative changes in muscle-tendon complex (MTC) properties following high load resistance training (RT) in young males and females, and determine any link with circulating TGFbeta-1 and IGF-I levels. METHODS: Twenty-eight participants were assigned to a training group and subdivided by sex (T males [TM] aged 20+/-1 year, n = 8, T females [TF] aged 19+/ 3 year, n = 8), whilst age-matched 6 males and 6 females were assigned to control groups (ConM/F). The training groups completed 8 weeks of resistance training (RT). MTC properties (Vastus Lateralis, VL) physiological cross-sectional area (pCSA), quadriceps torque, patella tendon stiffness [K], Young's modulus, volume, cross-sectional area, and length, circulating levels of TGFbeta-1 and IGF-I were assessed at baseline and post RT. RESULTS: Post RT, there was a significant increase in the mechanical and morphological properties of the MTC in both training groups, compared to ConM/F (p<0.001). However, there were no significant sex-specific changes in most MTC variables. There were however significant sex differences in changes in K, with females exhibiting greater changes than males at lower MVC (Maximal Voluntary Contraction) force levels (10% p = 0.030 & 20% MVC p = 0.032) and the opposite effect seen at higher force levels (90% p = 0.040 & 100% MVC p = 0.044). There were significant increases (p<0.05) in IGF-I in both TF and TM following training, with no change in TGFbeta-1. There were no gender differences (p>0.05) in IGF-I or TGFbeta-1. Interestingly, pooled population data showed that TGFbeta-1 correlated with K at baseline, with no correlations identified between IGF-I and MTC properties. CONCLUSIONS: Greater resting TGFbeta 1 levels are associated with superior tendon mechanical properties. RT can impact opposite ends of the patella tendon force-elongation relationship in each sex. Thus, different loading patterns may be needed to maximize resistance training adaptations in each sex. PMID- 29787585 TI - Correction: Cardiorespiratory Fitness, Sedentary Behaviour and Physical Activity Are Independently Associated with the Metabolic Syndrome, Results from the SCAPIS Pilot Study. AB - [This corrects the article DOI: 10.1371/journal.pone.0131586.]. PMID- 29787586 TI - Procrustes-based geometric morphometrics on MRI images: An example of inter operator bias in 3D landmarks and its impact on big datasets. AB - Using 3D anatomical landmarks from adult human head MRIs, we assessed the magnitude of inter-operator differences in Procrustes-based geometric morphometric analyses. An in depth analysis of both absolute and relative error was performed in a subsample of individuals with replicated digitization by three different operators. The effect of inter-operator differences was also explored in a large sample of more than 900 individuals. Although absolute error was not unusual for MRI measurements, including bone landmarks, shape was particularly affected by differences among operators, with up to more than 30% of sample variation accounted for by this type of error. The magnitude of the bias was such that it dominated the main pattern of bone and total (all landmarks included) shape variation, largely surpassing the effect of sex differences between hundreds of men and women. In contrast, however, we found higher reproducibility in soft-tissue nasal landmarks, despite relatively larger errors in estimates of nasal size. Our study exemplifies the assessment of measurement error using geometric morphometrics on landmarks from MRIs and stresses the importance of relating it to total sample variance within the specific methodological framework being used. In summary, precise landmarks may not necessarily imply negligible errors, especially in shape data; indeed, size and shape may be differentially impacted by measurement error and different types of landmarks may have relatively larger or smaller errors. Importantly, and consistently with other recent studies using geometric morphometrics on digital images (which, however, were not specific to MRI data), this study showed that inter-operator biases can be a major source of error in the analysis of large samples, as those that are becoming increasingly common in the 'era of big data'. PMID- 29787587 TI - Application of individual behavioral models to predict willingness to use modern contraceptives among pastoralist women in Afar region, Northern Ethiopia. AB - BACKGROUND: Use of modern contraceptive methods reduces the risk of unwanted pregnancy, and is influenced by individual-level factors. Willingness to use modern contraceptive methods maybe a useful metric when considering health outcomes as it could predict health behaviors. Therefore, the current study aimed to assess the willingness of women to use modern contraceptives in Afar pastoralist communities. METHODS: A community-based cross-sectional study was conducted from May 1 to 30, 2016. Three hundred forty-five women of childbearing age (15-49 years) were systematically sampled with proportionate allocation from seven randomly selected kebeles (neighborhoods) in Aballa District of Afar Region, Ethiopia. All women meeting the inclusion criteria in each selected household were interviewed at home using a semi-structured questionnaire. Construct validity was assured using factor analysis. A combination of individual behavioral models were applied in order to measure willingness to use modern contraceptive methods. Multiple logistic regressions were utilized to identify factors associated with willingness to use contraceptive at P-value of less than 0.05. RESULTS: Three hundred twenty-two women participated in the study, for a response rate of 93.3%. The mean age of respondents was 27 (+/-6) years. About one-third (N = 106, 32.9%) of the participants reported that they were willing to use modern contraceptives. Orthodox Christians (AOR = 4.22, 95% CI 1.94-8.92), women aged 19 or older at first marriage (AOR = 2.89, 95% CI 1.16-7.23), and women who had never experienced a stillbirth (AOR = 3.85, 95%CI 1.37-10.78) were more likely to report being willing to use modern contraceptives. Additionally, perceived severity of an unwanted pregnancy (AOR = 1.71, 95% CI 1.57-1.93) and perceived self-efficacy to use contraceptives (AOR = 1.26, 95% CI 1.17-1.65) were positively associated with the willingness. Women who had never had an abortion were less likely to express willingness to use modern contraceptives (AOR = 0.41, 95% CI 0.19-0.92) and perceived importance of cultural and religious norms (AOR = 0.85, 95% CI 0.62-0.90) was also negatively associated with willingness. CONCLUSIONS: The majority of women in this study were not willing to use modern contraceptive methods. A previous pregnancy outcome of stillbirth was associated with reduced willingness, while a prior abortion was associated with increased willingness. Perceived severity of unwanted pregnancy and higher self-efficacy surrounding contraceptive use were strong predictors of increased willingness to use contraceptives. Religious and cultural norms also appear to influence perception towards modern contraception. Thus, involvement of cultural and religious leaders and consideration of a woman's reproductive history are recommended when designing health education messages on contraception for Afar pastoralist women. PMID- 29787584 TI - Method overtness, forensic autopsy, and the evidentiary suicide note: A multilevel National Violent Death Reporting System analysis. AB - OBJECTIVE: Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note. METHODS: This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States National Violent Death Reporting System throughout 2011-2013, the study population comprised registered suicides, aged 15 years and older. Decedents totaled 32,151. The outcome measure was relative odds of an authenticated suicide note. RESULTS: An authenticated suicide note was documented in 31% of the suicide cases. Inspection of the full multivariable model showed a suicide note was more likely to manifest among drug intoxication (adjusted odds ratio [OR], 1.70; 95% CI, 1.56, 1.85) and other poisoning suicides (OR, 2.12; 1.85, 2.42) than firearm suicides, the referent. Respective excesses were larger when there was no autopsy or autopsy status was unknown (OR, 1.86; 95% CI, 1.61, 2.14) and (OR, 2.25; 95% CI, 1.86, 2.72) relative to the comparisons with a forensic autopsy (OR, 1.62, 95% CI, 1.45, 1.82 and OR, 2.01; 95% CI, 1.66, 2.43). Hanging/suffocation suicides did not differ from the firearm referent given an autopsy. CONCLUSIONS: Suicide requires substantial affirmative evidence to establish manner of death, and affirmation of drug intoxication suicides appears to demand an especially high burden of proof. Findings and their implications argue for more stringent investigative standards, better training, and more resources to support comprehensive and accurate case ascertainment, as the foundation for developing evidence-based suicide prevention initiatives. PMID- 29787588 TI - Angiogenic and pleiotropic effects of VEGF165 and HGF combined gene therapy in a rat model of myocardial infarction. AB - Since development of plasmid gene therapy for therapeutic angiogenesis by J. Isner this approach was an attractive option for ischemic diseases affecting large cohorts of patients. However, first placebo-controlled clinical trials showed its limited efficacy questioning further advance to practice. Thus, combined methods using delivery of several angiogenic factors got into spotlight as a way to improve outcomes. This study provides experimental proof of concept for a combined approach using simultaneous delivery of VEGF165 and HGF genes to alleviate consequences of myocardial infarction (MI). However, recent studies suggested that angiogenic growth factors have pleiotropic effects that may contribute to outcome so we expanded focus of our work to investigate potential mechanisms underlying action of VEGF165, HGF and their combination in MI. Briefly, Wistar rats underwent coronary artery ligation followed by injection of plasmid bearing VEGF165 or HGF or mixture of these. Histological assessment showed decreased size of post-MI fibrosis in both-VEGF165- or HGF-treated animals yet most prominent reduction of collagen deposition was observed in VEGF165+HGF group. Combined delivery group rats were the only to show significant increase of left ventricle (LV) wall thickness. We also found dilatation index improved in HGF or VEGF165+HGF treated animals. These effects were partially supported by our findings of c-kit+ cardiac stem cell number increase in all treated animals compared to negative control. Sporadic Ki-67+ mature cardiomyocytes were found in peri-infarct area throughout study groups with comparable effects of VEGF165, HGF and their combination. Assessment of vascular density in peri-infarct area showed efficacy of both-VEGF165 and HGF while combination of growth factors showed maximum increase of CD31+ capillary density. To our surprise arteriogenic response was limited in HGF-treated animals while VEGF165 showed potent positive influence on a-SMA+ blood vessel density. The latter hinted to evaluate infiltration of monocytes as they are known to modulate arteriogenic response in myocardium. We found that monocyte infiltration was driven by VEGF165 and reduced by HGF resulting in alleviation of VEGF-stimulated monocyte taxis after combined delivery of these 2 factors. Changes of monocyte infiltration were concordant with a-SMA+ arteriole density so we tested influence of VEGF165 or HGF on endothelial cells (EC) that mediate angiogenesis and inflammatory response. In a series of in vitro experiments we found that VEGF165 and HGF regulate production of inflammatory chemokines by human EC. In particular MCP-1 levels changed after treatment by recombinant VEGF, HGF or their combination and were concordant with NF-kappaB activation and monocyte infiltration in corresponding groups in vivo. We also found that both-VEGF165 and HGF upregulated IL-8 production by EC while their combination showed additive type of response reaching peak values. These changes were HIF-2 dependent and siRNA-mediated knockdown of HIF-2alpha abolished effects of VEGF165 and HGF on IL-8 production. To conclude, our study supports combined gene therapy by VEGF165 and HGF to treat MI and highlights neglected role of pleiotropic effects of angiogenic growth factors that may define efficacy via regulation of inflammatory response and endothelial function. PMID- 29787589 TI - High seroprevalence of hepatitis E virus in the ethnic minority populations in Yunnan, China. AB - Hepatitis E virus (HEV) infection is relatively high in the southern regions of China. Yunnan, located in southwestern China, has the highest number of ethnic groups. However, HEV infection in the ethnic population is largely unknown. Therefore, we aimed to investigate the seropositive rate, risk factor, and clinical impact of HEV infection in the ethnic groups of Yunnan. We recruited 1912 individuals from four minority groups in three prefectures of Yunnan province. Epidemiological records on potential risk factors for exposure to HEV and blood biochemical index were analyzed. All the serum samples were tested for anti-HEV IgM/IgG by enzyme-linked immunosorbent assay, and the IgM-positive samples were subjected to nested reverse transcription-PCR to detect HEV RNA. Overall, 1273 individuals (66.58%) were positive for anti-HEV IgG, 16 (0.84%) for anti-HEV IgM, and 64 (3.35%) for anti-HEV IgG and IgM both; none of them had detectable HEV RNA. Multivariate analysis revealed a strong statistical association between ethnic origin and HEV IgG seroprevalence. Anti-HEV IgG reactivity in the Hani ethnic (82.3%; 401/487) population was higher than that in the Naxi (71.9%, 340/473), Bulang (65.1%; 302/464), and Wa (60.2%; 294/488) ethnic populations (p < 0.0001). Older age and male sex were independently associated with the risk of past HEV infection. Moreover, anti-HEV IgG-positive individuals showed significantly higher levels of total and direct bilirubin and alanine amino transferase but significantly lower levels of globulin and low density lipoprotein, than the respective levels in anti-HEV IgG-negative individuals. Thus, the seroprevalence of HEV infection is high in the ethnic populations of Yunnan, China. It is therefore necessary to increase the surveillance of specific risk groups and raise awareness about the possible infectious diseases to help limit the HEV transmission here. PMID- 29787590 TI - Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules. AB - OBJECTIVE: Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5-60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)-Early Cancer Detection Test-Lung (EarlyCDT-LungTM)-as an aid to early diagnosis of lung cancer among such patients. METHODS: We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT-because they are at substantially enhanced risk of lung cancer-are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed on average-at more advanced stages. RESULTS: Among 1,000 patients who have incidentally detected nodules 8-30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833. CONCLUSIONS: Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources. PMID- 29787592 TI - Which antiarrhythmic drug to choose after electrical cardioversion: A study on non-valvular atrial fibrillation patients. AB - The relative efficacy of antiarrhythmic drugs (AADs) after electrical cardioversion are not well established. This study aimed to investigate the efficacies of different AADs for maintaining sinus rhythm (SR) after electrical cardioversion for atrial fibrillation (AF). We selected patients from a retrospective registry including patients admitted for cardioversion between January 2012 and June 2016. The primary outcome was time to AF recurrence during the first year after cardioversion. The secondary outcomes included AF recurrence within 1 month, and first readmission due to heart failure, stroke, or additional non-pharmacological rhythm control. A total of 265 patients were divided into the 4 groups according to AAD type: flecainide (n = 33), propafenone (n = 64), amiodarone (n = 128), and dronedarone (n = 40). During the first year after cardioversion, the AF recurrence-free survival was similar between all AAD groups (69.7% vs. 67.2% vs. 71.9% vs. 80.0%, p = 0.439). About half of all recurrences occurred during the first month. There was no difference in any of the secondary outcomes, although the amiodarone group showed a trend toward more non pharmacological rhythm control. AAD type was not associated with recurrence in multivariate analysis. In this study, half of all patients received amiodarone after electrical cardioversion. Flecainide, propafenone, amiodarone, and dronedarone showed similar efficacies for maintaining SR after electrical cardioversion. Thus, it might be reasonable to reconsider amiodarone use after cardioversion, since it did not show superior efficacy to the other drugs considered and is associated with potential side effects. PMID- 29787593 TI - Improving the effectiveness of performance feedback by considering personality traits and task demands. AB - Although performance feedback is widely employed as a means to improve motivation, the efficacy and reliability of performance feedback is often obscured by individual differences and situational variables. The joint role of these moderating variables remains unknown. Accordingly, we investigate how the motivational impact of feedback is moderated by personality and task-difficulty. Utilizing three samples (total N = 916), we explore how Big Five personality traits moderate the motivational impact of false positive and negative feedback on playful, neutral, and frustrating puzzle tasks, respectively. Conscientious and Neurotic individuals together appear particularly sensitive to task difficulty, becoming significantly more motivated by negative feedback on playful tasks and demotivated by negative feedback on frustrating tasks. Results are discussed in terms of Goal-Setting and Self Determination Theory. Implications for industry and education are considered. PMID- 29787594 TI - Is Community-Led Total Sanitation connected to the rebuilding of latrines? Quantitative evidence from Mozambique. AB - To reduce open defecation, many implementers use the intervention strategies of Community-Led Total Sanitation (CLTS). But CLTS focuses on latrine construction and does not include latrine maintenance and repair damage or collapse. Some households rebuild their latrine while others return to open defecation. The reasons why are unknown. Using data from a cross-sectional survey, this article shows how physical, personal, and social context factors and psychosocial factors from the RANAS model are associated with CLTS participation, and how these factors connect to latrine rebuilding. In 2015, heavy rains hit the north of Mozambique and many latrines collapsed. Subsequently, 640 household interviews were conducted in the affected region. Logistic regression and mediation analyses reveal that latrine rebuilding depends on education, soil conditions, social cohesion, and a feeling of being safe from diarrhea, the perception that many other community members own a latrine, and high confidence in personal ability to repair or rebuild a broken latrine. The effect of CLTS is mediated through social and psychosocial factors. CLTS already targets most of the relevant factors, but can still be improved by including activities that would focus on other factors not yet sufficiently addressed. PMID- 29787591 TI - Pharmacophore modeling for identification of anti-IGF-1R drugs and in-vitro validation of fulvestrant as a potential inhibitor. AB - Insulin-like growth factor 1 receptor (IGF-1R) is an important therapeutic target for breast cancer treatment. The alteration in the IGF-1R associated signaling network due to various genetic and environmental factors leads the system towards metastasis. The pharmacophore modeling and logical approaches have been applied to analyze the behaviour of complex regulatory network involved in breast cancer. A total of 23 inhibitors were selected to generate ligand based pharmacophore using the tool, Molecular Operating Environment (MOE). The best model consisted of three pharmacophore features: aromatic hydrophobic (HyD/Aro), hydrophobic (HyD) and hydrogen bond acceptor (HBA). This model was validated against World drug bank (WDB) database screening to identify 189 hits with the required pharmacophore features and was further screened by using Lipinski positive compounds. Finally, the most effective drug, fulvestrant, was selected. Fulvestrant is a selective estrogen receptor down regulator (SERD). This inhibitor was further studied by using both in-silico and in-vitro approaches that showed the targeted effect of fulvestrant in ER+ MCF-7 cells. Results suggested that fulvestrant has selective cytotoxic effect and a dose dependent response on IRS-1, IGF-1R, PDZK1 and ER-alpha in MCF-7 cells. PDZK1 can be an important inhibitory target using fulvestrant because it directly regulates IGF 1R. PMID- 29787595 TI - Current and previous spatial distributions of oilseed rape fields influence the abundance and the body size of a solitary wild bee, Andrena cineraria, in permanent grasslands. AB - Wild bees are essential pollinators whose survival partly depends on the capacity of their environment to offer a sufficient amount of nectar and pollen. Semi natural habitats and mass-flowering crops such as oilseed rape provide abundant floristic resources for bees. The aim of this study was to evaluate the influences of the spatial distribution of semi-natural habitats and oilseed rape fields on the abundance and the mean body size of a solitary bee in grasslands. We focused on a generalist mining bee, Andrena cineraria, that forages and reproduces during oilseed rape flowering. In 21 permanent grasslands of Eastern France, we captured 1 287 individuals (1 205 males and 82 females) and measured the body size of male individuals. The flower density in grasslands was quantified during bee captures (2016) and the landscape surrounding grasslands was characterized during two consecutive years (2015 and 2016). The influence of oilseed rape was tested through its distribution in the landscape during both the current year of bee sampling and the previous year. Bee abundance was positively influenced by the flower density in grasslands and by the area covered by oilseed rape around grasslands in the previous year. The mean body size of A. cineraria was explained by the interaction between flower density in the grassland and the distance to the nearest oilseed rape field in the current year: the flower density positively influenced the mean body size only in grasslands distant from oilseed rape. A. cineraria abundance and body size distribution were not affected by the area of semi-natural habitats in the landscape. The spatial distribution of oilseed rape fields (during both the current and the previous year) as well as the local density of grassland flowers drive both bee abundance and the mean value of an intraspecific trait (body size) in permanent grasslands. Space-time variations of bee abundance and mean body size in grasslands may have important ecological implications on plant pollination and on interspecific interactions between pollinators. Specifically, a competition between bee species for nesting sites might occur in oilseed rape rich landscapes, thus raising important conservation issues for bee species that do not benefit from oilseed rape resources. PMID- 29787596 TI - Survival and predictors of mortality among children co-infected with tuberculosis and human immunodeficiency virus at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A retrospective follow-up study. AB - BACKGROUND: Tuberculosis (TB) is the leading cause of death in Human immunodeficiency virus (HIV) infected children globally. The aims of this study were to determine the mortality rate and to identify the predictors of mortality among TB/HIV co-infected children at University of Gondar Comprehensive Specialized Hospital. METHOD: A retrospective follow-up study was conducted among TB/HIV co-infected children from February 2005 to March 2017. A Kaplan-Meier curve was used to estimate the median survival time. Bivariate and multivariable Cox proportional hazards models were fitted to identify the predictors of mortality. RESULTS: A total of 271 TB/HIV co-infected children were included in the analysis. Of these, 38(14.02%) children were died during the follow-up period. This gives a total of 1167.67 child-years of observations. The overall mortality rate was 3.27(95%CI: 2.3-4.5) per 100 child-years. The independent predictors of time to death were age 1-5 years (as compared to age <1 year) (AHR = 0.3; 95%CI:0.09-0.98)), being anemic (AHR = 2.6; 95%CI:1.24-5.3), cotrimoxazole preventive therapy(CPT) non-users (AHR = 4.1; 95%CI:1.4-16.75), isoniazid preventive therapy(IPT) non-users (AHR = 2.95; 95%CI:1.16-7.5), having extra pulmonary tuberculosis(EPTB) (AHR = 2.43; 95%CI:1.1-5.3)) and fair or poor adherence to Anti-Retroviral Therapy (ART)(AHR = 3.5; 95%CI:1.7-7.5). CONCLUSION: Mortality rate among TB/HIV co-infected children was high at University of Gondar Comprehensive Specialized Hospital. Age, extra-pulmonary tuberculosis, anemia, adherence, CPT and IPT were the independent predictors of mortality. PMID- 29787598 TI - A citizen science based survey method for estimating the density of urban carnivores. AB - Globally there are many examples of synanthropic carnivores exploiting growth in urbanisation. As carnivores can come into conflict with humans and are potential vectors of zoonotic disease, assessing densities in suburban areas and identifying factors that influence them are necessary to aid management and mitigation. However, fragmented, privately owned land restricts the use of conventional carnivore surveying techniques in these areas, requiring development of novel methods. We present a method that combines questionnaire distribution to residents with field surveys and GIS, to determine relative density of two urban carnivores in England, Great Britain. We determined the density of: red fox (Vulpes vulpes) social groups in 14, approximately 1km2 suburban areas in 8 different towns and cities; and Eurasian badger (Meles meles) social groups in three suburban areas of one city. Average relative fox group density (FGD) was 3.72 km-2, which was double the estimates for cities with resident foxes in the 1980's. Density was comparable to an alternative estimate derived from trapping and GPS-tracking, indicating the validity of the method. However, FGD did not correlate with a national dataset based on fox sightings, indicating unreliability of the national data to determine actual densities or to extrapolate a national population estimate. Using species-specific clustering units that reflect social organisation, the method was additionally applied to suburban badgers to derive relative badger group density (BGD) for one city (Brighton, 2.41 km-2). We demonstrate that citizen science approaches can effectively obtain data to assess suburban carnivore density, however publicly derived national data sets need to be locally validated before extrapolations can be undertaken. The method we present for assessing densities of foxes and badgers in British towns and cities is also adaptable to other urban carnivores elsewhere. However this transferability is contingent on species traits meeting particular criteria, and on resident responsiveness. PMID- 29787597 TI - Asymmetric and symmetric dimethylarginines and mortality in patients with hematological malignancies-A prospective study. AB - The study was designed to determine the associations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines plasma concentrations with all-cause mortality in patients with hematological malignancies. 33 patients with acute myeloid leukemia (AML), 31 patients with non-Hodgkin's lymphoma (nHL), 32 patients with chronic lymphocytic leukemia (CLL) and 48 patients without malignancy were enrolled into the study. Each patient was followed until death or for at least 14.5 months (range: 14.5-53). Median ADMA and SDMA were significantly elevated in AML, nHL and CLL compared to controls (ADMA: 1.36, 1.24, 1.03, 0.55 MUmol/l respectively, p<0.0001; SDMA: 0.86, 0.76, 0.71, 0.52 MUmol/l respectively, p<0.0001). High ADMA and SDMA were associated with increased risk for all-cause mortality in CLL group (Hazard ratio (HR) for ADMA: 3.05, 95% CI:1.58-5.88, p = 0.001; HR for SDMA: 4.71, 95% CI:1.91-11.58, p = 0.001). Our study suggests that ADMA and SDMA could be novel prognostic factors for all-cause mortality in CLL patients. PMID- 29787600 TI - Correction: The Effect of Timing and Frequency of Push Notifications on Usage of a Smartphone-Based Stress Management Intervention: An Exploratory Trial. AB - [This corrects the article DOI: 10.1371/journal.pone.0169162.]. PMID- 29787599 TI - Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis. AB - Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease characterized by corneal endothelial decompensation. FECD causes corneal stromal and epithelial edema and progressively develops into bullous keratopathy, which can eventually lead to blindness. However, the exact pathogenesis is unknown. In this study, we performed an in-depth bioinformatic analysis of the dataset GSE74123 to determine the differentially expressed genes (DEGs) of symptomatic late-onset FECD compared with a normal control. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the pathological molecular mechanism of FECD. We found that cell senescence, reactive oxygen species (ROS), the extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and immune response-related genes play an important role in the pathological development of symptomatic late-onset FECD. In addition, we revealed that down-regulated IL-6, enhanced NF-kappaB activity and a suite of orchestrated chemokine responses induce fibrocyte differentiation from monocyte to dendritic cell maturation. PI3K plays a key role in the molecular mechanism of symptomatic late-onset FECD. This study enhances our understanding of the molecular mechanism of FECD pathogenesis and will improve the diagnostics and therapy of FECD patients in the future. PMID- 29787601 TI - Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms. AB - Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms. PMID- 29787602 TI - Endocrine disrupting potency of organic pollutant mixtures isolated from commercial fish oil evaluated in yeast-based bioassays. AB - The aim of this work was to evaluate the activity of xenobiotic mixtures containing persistent organic pollutants isolated from commercial fish oil samples against sex hormone receptors, including estrogen and androgen. The applied bioassay was based on transgenic yeast strains. The mixtures were extracted from the samples using the semi-permeable membrane dialysis technique and analyzed with gas chromatography/ion trap mass spectrometry. It turned out that mixtures of chemicals isolated from fish oil may interact with human steroid sex hormone receptors in various ways: the tested samples showed both estrogenic and anti-androgenic activity. Calculated 17beta-estradiol equivalents for the tested samples ranged between 0.003 and 0.073 pg g-1 (fat). Anti-androgenic activity expressed as the flutamide equivalent concentration was in the 18.58 216.21 ng g-1 (fat) range. Polychlorinated biphenyls and various DDT metabolites were the main fish oil pollutants influencing the receptors. Additivity and/or synergy between chemicals was observed in the ER/AR mediated response. PMID- 29787603 TI - Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness. AB - BACKGROUND: Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS). METHODS: Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT). The association of age, sex, ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFLT was analysed using Pearson correlation coefficient and fitting a linear mixed model. RESULTS: In the univariable analysis highest correlations were found for axial length (r = -0.27), spherical equivalent (r = 0.24), and glaucoma (r = -0.15) (p<0.0001, respectively). Other significant correlations with RNFLT were found for age, sex, intraocular pressure, systemic hypertension and systolic blood pressure, previous eye surgery, cholesterol, homocysteine, history of coronary artery disease, history of myocardial infarction, apnoea, diabetes and alcohol intake, p<0.05, respectively. Body length, body weight, BMI, diastolic blood pressure, blood glucose, HbA1c, history of apoplexy, cognitive function, peripheral artery disease, tinnitus, migraine, nicotine intake, central corneal thickness, and pseudophakia were not significantly correlated with RNFLT. The regression model revealed a significant relationship between RNFLT and age in decades (p<0.02), spherical equivalent (p<0.0001), axial length (p<0.0001), glaucoma (p<0.0001), tinnitus (p = 0.04), apnoea (p = 0.047), homocysteine (p = 0.05) and alcohol intake >10g/d for women and >20g/d for men (p = 0.02). Glaucoma, apnoea, higher homocysteine, higher alcohol intake and higher axial length as well as age were related to decreased RNFLT while higher spherical equivalent or history for tinnitus were related to thicker RNFL. CONCLUSION: RNFLT is related to age, ocular parameters and lifestyle factors. Considering these parameters in normative databases could improve the evaluation of peripapillary RNFLT. It is necessary to evaluate if a reduction of alcohol intake as well as the therapy of apnea or high homocysteine levels could positively influence RNFLT. PMID- 29787605 TI - Correction: Evaluating signals of oil spill impacts, climate, and species interactions in Pacific herring and Pacific salmon populations in Prince William Sound and Copper River, Alaska. AB - [This corrects the article DOI: 10.1371/journal.pone.0172898.]. PMID- 29787604 TI - Laparoscopic uterine surgery as a risk factor for uterine rupture during pregnancy. AB - The incidence of uterine rupture through a previous cesarean scar (CS) is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes). Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%), 13 through a non cesarean scar (non-CS ruptures, 59%), whereas the remaining two (9%) were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76%) occurred after a previous laparoscopic myomectomy, one (8%) following a hysteroscopic myomectomy, and two (16%) after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL) requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024). Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy. PMID- 29787606 TI - Profiling neurotransmitters in a crustacean neural circuit for locomotion. AB - Locomotor systems are widely used to study rhythmically active neural networks. These networks have to be coordinated in order to produce meaningful behavior. The crayfish swimmeret system is well suited to investigate such coordination of distributed neural oscillators because the neurons and their connectivity for generating and especially for coordinating the motor output are identified. The system maintains a fixed phase lag between the segmental oscillators, independent of cycle period. To further the understanding of the system's plasticity for keeping the phase lag fixed, we profiled the neurotransmitters used by the Coordinating Neurons, which are necessary and sufficient for coordination of the segmental oscillators. We used a combination of electrophysiological, immunohistochemical, and mass spectrometric methods. This arrangement of methods ensured that we could screen for several specific neurotransmitters, since a single method is often not suitable for all neurotransmitters of interest. In a first step, to preselect neurotransmitter candidates, we investigated the effect of substances known to be present in some swimmeret system neurons on the motor output and coordination. Subsequently, we demonstrated electrophysiologically that the identified synapse between the Coordinating Neurons and their target is mainly chemical, but neither glutamate antagonist nor gamma-aminobutyric acid antagonist application affected this synapse. With immunohistochemical experiments, we provide strong evidence that the Coordinating Neurons are not serotonergic. Single-cell MALDI-TOF mass spectrometry with subsequent principal component analysis identified acetylcholine as the putative neurotransmitter for both types of Coordinating Neurons. PMID- 29787607 TI - Differential sequences of exosomal NANOG DNA as a potential diagnostic cancer marker. AB - NANOG has been demonstrated to play an essential role in the maintenance of embryonic stem cells, and its pseudogene, NANOGP8, is suggested to promote the cancer stem cell phenotype. As the roles of these genes are intimately involved with glioblastoma multiforme progression and exosomes are critical in intercellular communication, we conducted a detailed analysis of the association of the NANOG gene family with exosomes to identify diagnostic markers for cancer. Exosomes were precipitated from conditioned culture media from various cell lines, and NANOG gene fragments were directly amplified without DNA isolation using multiple primer sets. The use of the enzymes AlwNI and SmaI with restriction fragment length polymorphism analysis functioned to distinguish NANOGP8 from other NANOG family members. Collectively, results suggest that the NANOG DNA associated with exosomes is not full length and that mixed populations of the NANOG gene family exist. Furthermore, sequence analysis of exosomal DNA amplified with a NANOGP8 specific primer set frequently showed an insertion of a 22 bp sequence into the 3' UTR. The occurrence rate of this insertion was significantly higher in exosomal DNA clones from cancer cells as compared to normal cells. We have detected mixed populations of NANOG DNA associated with exosomes and have identified preferential modulations in the sequences from cancer samples. Our findings, coupled with the properties of exosomes, may allow for the detection of traditionally inaccessible cancers (i.e. GBM) through minimally invasive techniques. Further analysis of exosomal DNA sequences of NANOG and other embryonic stemness genes (OCT3/4, SOX2, etc.) may establish a robust collection of exosome based diagnostic markers, and further elucidate the mechanisms of cancer formation, progression, and metastasis. PMID- 29787608 TI - Loci under selection and markers associated with host plant and host-related strains shape the genetic structure of Brazilian populations of Spodoptera frugiperda (Lepidoptera, Noctuidae). AB - We applied the ddRAD genotyping-by-sequencing technique to investigate the genetic distinctiveness of Brazilian populations of the noctuid moth Spodoptera frugiperda, the fall armyworm (FAW), and the role of host-plant association as a source of genetic diversification. By strain-genotyping all field-collected individuals we found that populations collected from corn were composed primarily of corn-strain individuals, while the population collected from rice was composed almost entirely of rice-strain individuals. Outlier analyses indicated 1,184 loci putatively under selection (ca. 15% of the total) related to 194 different Gene Ontologies (GOs); the most numerous GOs were nucleotide binding, ATP binding, metal-ion binding and nucleic-acid binding. The association analyses indicated 326 loci associated with the host plant, and 216 loci associated with the individual strain, including functions related to Bacillus thuringiensis and insecticide resistance. The genetic-structure analyses indicated a moderate level of differentiation among all populations, and lower genetic structure among populations collected exclusively from corn, which suggests that the population collected from rice has a strong influence on the overall genetic structure. Populations of S. frugiperda are structured partially due to the host plant, and pairs of populations using the same host plant are more genetically similar than pairs using different hosts. Loci putatively under selection are the main factors responsible for the genetic structure of these populations, which indicates that adaptive selection on important traits, including the response to control tactics, is acting in the genetic differentiation of FAW populations in Brazil. PMID- 29787610 TI - The influence of somatotype on anaerobic performance. AB - The link between athlete physique and performance in sports is well established. However, a direct link between somatotype three-numeral rating and anaerobic performance has not yet been reported. The purpose of this study was to assess the relations between somatotype and anaerobic performance using both singular and multivariate analyses. Thirty-six physically active males (mean +/- standard deviation age 26.0 +/- 9.8 years; body mass 79.5 +/- 12.9 kg; height 1.82 +/- 0.07 m) were somatotype-rated using the Heath-Carter method. Subjects were assessed for 3 repetition maximum (3 RM) bench press and back squat, and completed a 30-second maximal sprint cycle test. Positive correlations were observed between mesomorphy and 3 RM bench press (r = 0.560, p < 0.001), mesomorphy and 3 RM back squat (r = 0.550, p = 0.001) and between mesomorphy and minimum power output (r = 0.357, p = 0.033). Negative correlations were observed between ectomorphy and 3 RM bench press (r = -0.381, p = 0.022), and ectomorphy and 3 RM back squat (r = -0.336, p = 0.045). Individual regression analysis indicated that mesomorphy was the best predictor of 3 RM bench press performance, with 31.4% of variance in 3 RM bench press performance accounted for by the mesomorphy rating (p < 0.001). A combination of mesomorphy and ectomorphy best predicted 3 RM back squat performance (R2 = 0.388, p < 0.04). Around one third of strength performance is predicted by somatotype-assessed physique in physically active males. This could have important implications for the identification of those predisposed to perform well in sports containing strength-based movements and prescription of training programmes. PMID- 29787609 TI - An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging. AB - BACKGROUND: Understanding how vascular and metabolic factors impact on cognitive function is essential to develop efficient therapies to prevent and treat cognitive losses in older age. Cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and venous oxygenation (Yv) comprise key physiologic processes that maintain optimum functioning of neural activity. Changes to these parameters across the lifespan may precede neurodegeneration and contribute to age-related cognitive decline. This study examined differences in blood flow and metabolism between 31 healthy younger (<50 years) and 29 healthy older (>50 years) adults; and investigated whether these parameters contribute to cognitive performance. METHOD: Participants underwent a cognitive assessment and MRI scan. Grey matter CMRO2 was calculated from measures of CBF (phase contrast MRI), arterial and venous oxygenation (TRUST MRI) to assess group differences in physiological function and the contribution of these parameters to cognition. RESULTS: Performance on memory (p<0.001) and attention tasks (p<0.001) and total CBF were reduced (p<0.05), and Yv trended toward a decrease (p = .06) in the older group, while grey matter CBF and CMRO2 did not differ between the age groups. Attention was negatively associated with CBF when adjusted (p<0.05) in the older adults, but not in the younger group. There was no such relationship with memory. Neither cognitive measure was associated with oxygen metabolism or venous oxygenation in either age group. CONCLUSION: Findings indicated an age related imbalance between oxygen delivery, consumption and demand, evidenced by a decreased supply of oxygen with unchanged metabolism resulting in increased oxygen extraction. CBF predicted attention when the age-effect was controlled, suggesting a task- specific CBF- cognition relationship. PMID- 29787611 TI - Evaluation of anaesthetic protocols for laboratory adult zebrafish (Danio rerio). AB - In the last decades, the use of zebrafish (Danio rerio) in biomedical research has increased. Anaesthesia is daily used in fish during experimental procedures to avoid discomfort, stress or pain. Also, fish welfare and the reliability of results can be compromised if an unsuitable anaesthetic protocol is used. Therefore, we aimed to refine anaesthetic protocols to be used in adult zebrafish by evaluating the efficacy of different anaesthetics, used alone or in combination. For that, zebrafish were randomly assigned to 8 different groups: 100 MUg/mLMS-222 (MS); 0.2 MUg/mL etomidate (E); 0.2 MUg/mL etomidate + 100 MUg/mL lidocaine (E+L); 1.25 MUg/mL propofol (P); 1.25 MUg/mL propofol + 100 MUg/mL lidocaine (P+L); 100 MUg/mL ketamine (K); 100 MUg/mL ketamine + 1.25 MUg/mL medetomidine (K+M); and 100 MUg/mL ketamine + 1.25 MUg/mL medetomidine/3.125 MUg/mL atipamezole (K+M/A). The animals were placed in an anaesthetic water bath, then, the following parameters were registered: time for equilibrium loss and anaesthesia induction, loss of sensitivity to soft and painful stimuli, respiratory rate, recovery time, and activity after recovery. The combined forms of E+L, P+L and K+M were the fastest to induce a surgical anaesthetic stage. Nevertheless, E+L induced respiratory depression, while K+M was shown to have the longer recovery time compared to MS-222, even when atipamezole was added. In conclusion, the P+L combination was shown to provide good anaesthesia with analgesia, without causing a major respiratory depression, providing as well a quick recovery, similar to MS-222. PMID- 29787613 TI - Clinical and functional outcomes of vascularized bone graft in the treatment of scaphoid non-union. AB - INTRODUCTION: Scaphoid non-union is a challenging and complex problem. Various methods have been proposed for the management of patients with scaphoid non-union and to reduce the risk of complications. In this study, our aim was to evaluate the clinical and functional outcomes of using a vascularized bone graft in the treatment of scaphoid non-union. METHODS: Patients with scaphoid non-union who underwent 1,2 intercompartmental supraretinacular artery pedicled vascularized bone graft between January 2005 and January 2011 were enrolled. The parameters assessed included clinical and functional outcomes, radiological measures, and potential risk factors. RESULTS: Forty-one patients were finally included. Thirty patients achieved union (73%) and 11 did not. Smoking was a significant risk factor for non-union after the surgery. In patients who achieved union, grip strength and radioulnar abduction were greater in comparison to that in patients who did not achieve union. Functional measures, including the Disabilities of Arm and Shoulder score and the Modified Mayo Wrist Score, improved in patients with scaphoid union. The scaphoid length also improved significantly postoperatively in these patients. CONCLUSION: Surgical treatment of scaphoid non-union using vascularized bone graft led to a high union rate with good clinical and functional outcomes. Smoking is a risk factor for non-union, even with the use of a vascularized bone graft. Avascular necrosis was not associated with an increased risk for non-union. PMID- 29787614 TI - Outcome of polycystic kidney disease patients on peritoneal dialysis: Systematic review of literature and meta-analysis. AB - BACKGROUND: Polycystic kidney disease (PKD) is the most frequent hereditary cause of chronic kidney disease. Peritoneal dialysis (PD) is often avoided for patients with PKD because of the suspected risk of mechanical and infectious complications. Only a few studies have analyzed the outcome of PKD patients on PD with sometimes conflicting results. The purpose of this meta-analysis was to investigate outcomes of patients with PKD treated by PD. METHODS: A systematic review and meta-analysis were performed examining all studies which included "Polycystic kidney disease" and "Peritoneal dialysis" in their titles, excluding commentaries, letters to the authors and abstracts. PubMed, Embase, Google scholar and Scopus were searched to December 31st 2017. The primary outcome was overall patient survival. Additional outcomes were PD technique survival, incidence of peritonitis and incidence of abdominal wall hernia. RESULTS: 9 studies published between 1998 and 2016 were included for analysis with a total of 7,197 patients including 882 PKD patients. Overall survival of PKD patients was found to be better compared to non-PKD patients (HR = 0.70 [95% CI, 0.54 0.92]). There were no statistical differences between PKD and non-PKD patients in terms of peritonitis (OR = 0.86 [95% CI, 0.66-1.12]) and technical survival (HR = 0.98 [95% CI, 0.83-1.16]). There was an increased risk of hernia in PKD patients (OR = 2.28 [95% CI, 1.26-4.12]). CONCLUSIONS: PKD is associated with a better global survival, an increased risk of abdominal hernia, but no differences in peritonitis rate or technical survival were found. PD is a safe dialysis modality for PKD patients. Properly designed controlled studies are needed to determine whether all PKD patients are eligible for PD or whether some specific criteria should be determined. PMID- 29787612 TI - Psychosocial needs of young breast cancer survivors in Mexico City, Mexico. AB - OBJECTIVE: Young breast cancer survivors in Mexico face distinct psychosocial challenges that have not been characterized. This study aims to describe the psychosocial needs of young breast cancer survivors in Mexico at 5 or more years of survivorship, identifying areas of focus for early interventions. METHODS: Breast cancer patients diagnosed at age 40 or prior with 5 or more years since diagnosis were invited to participate in one-on-one 30-60 minute semi-structured audio-recorded interviews at the Instituto Nacional de Cancerologia in Mexico City. Transcripts were coded using thematic analysis with NVivo software. RESULTS: 25 women participated. Five major phenomena emerged from analysis: (1) minimization of fertility concerns; (2) persistence of body image disturbance over time; (3) barriers to employment during survivorship; (4) impact on family relationships and social networks; & (5) unmet psychological care and informational needs. CONCLUSIONS: Early interventions with a focus on fertility loss education, access to reconstructive surgery and body image support, guidance during return-to-work, assistance with childcare, integration of psychological care and the fulfillment of informational needs could ameliorate long-term psychological and social distress for young breast cancer survivors in Mexico. PMID- 29787615 TI - Plasma gelsolin is associated with hip BMD in Chinese postmenopausal women. AB - Gelsolin (GSN) protein, expressed in circulating monocytes, was previously reported to be associated with osteoporosis in both Chinese and Caucasian women. This study aims to test if plasma GSN protein level is associated with hip bone mineral density (BMD) in Chinese population. Based on two study Groups containing 6,308 old Chinese, we adopted extreme sampling scheme and selected 3 independent samples (Subgroups 1-3) for discovery, replication, and validation purposes. We tested plasma GSN concentration, and analyzed whether plasma GSN level differs between subjects with extremely low vs. high hip BMD. In Group 1 (N = 1,860), the plasma GSN level increased in the female with low BMD, which was discovered in the Subgroup 1 (N = 42, p = 0.093) and replicated in the Subgroup 2 (N = 39, p = 0.095). With more extreme sampling for the Subgroup 3 from the Group 2 (N = 4,448), the difference of plasma GSN level in the female with low BMD vs. high BMD is more significant (N = 45, p = 0.037). After the subjects were pooled from Subgroups 2 and 3, the difference in plasma GSN between low and high BMD subjects became even more significant (p = 0.016). The plasma GSN level was negatively correlated with total hip BMD (r = -0.26, p = 0.033). We concluded that plasma GSN was associated with hip BMD in Chinese postmenopausal women and plasma GSN might be a potential risk biomarker for osteoporosis. PMID- 29787616 TI - Efficacy and safety of saxagliptin in patients with type 2 diabetes: A systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs). RESULTS: Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c <7% (RR 1.64, 95% CI 1.53 to 1.75). When combined with submaximal dose metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide and dapagliflozin on glycemic control. Saxagliptin significantly decreased the incidences of overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin. Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and lower than sulfonylureas. Saxagliptin did not increase the risk of arthralgia, heart failure, pancreatitis and other adverse events. CONCLUSIONS: Generally, saxagliptin has similar efficacy compared with most oral antidiabetic drugs and may be more effective than acarbose, while having a better safety profile than both acarbose and sulfonylureas. PMID- 29787618 TI - Correction: Freshwater reservoir offsets and food crusts: Isotope, AMS, and lipid analyses of experimental cooking residues. AB - [This corrects the article DOI: 10.1371/journal.pone.0196407.]. PMID- 29787619 TI - Mutational analysis of CCM1, CCM2 and CCM3 in a Han Chinese cohort with multiple cerebral cavernous malformations in Taiwan. PMID- 29787617 TI - Intact memory for local and distal cues in male and female rats that lack adult neurogenesis. AB - The dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis. PMID- 29787620 TI - Intact goal-directed control in treatment-seeking drug users indexed by outcome devaluation and Pavlovian to instrumental transfer: critique of habit theory. AB - Animal studies have demonstrated that chronic exposure to drugs of abuse impairs goal-directed control over action selection indexed by the outcome-devaluation and specific Pavlovian to instrumental transfer procedures, suggesting this impairment might underpin addiction. However, there is currently only weak evidence for impaired goal-directed control in human drug users. Two experiments were undertaken in which treatment-seeking drug users and non-matched normative reference samples (controls) completed outcome-devaluation and specific Pavlovian to instrumental transfer procedures notionally translatable to animal procedures (Experiment 2 used a more challenging biconditional schedule). The two experiments found significant outcome-devaluation and specific Pavlovian to instrumental transfer effects overall and there was no significant difference between groups in the magnitude of these effects. Moreover, Bayes factor supported the null hypothesis for these group comparisons. Although limited by non-matched group comparisons and small sample sizes, the two studies suggest that treatment-seeking drug users have intact goal-directed control over action selection, adding uncertainty to already mixed evidence concerning the role of habit learning in human drug dependence. Neuro-interventions might seek to tackle goal-directed drug-seeking rather than habit formation in drug users. PMID- 29787621 TI - Recent evolution of the human skin barrier. AB - The skin is the first line of defense against the environment, with the epidermis as the outermost tissue providing much of the barrier function. Given its direct exposure to and encounters with the environment, the epidermis must evolve to provide an optimal barrier for the survival of an organism. Recent advances in genomics have identified a number of genes for the human skin barrier that have undergone evolutionary changes since humans diverged from chimpanzees. Here, we highlight a selection of key and innovative genetic findings for skin barrier evolution in our divergence from our primate ancestors and among modern human populations. PMID- 29787622 TI - Mother-to-child transmission of HIV in Australia and other high-income countries: Trends in perinatal exposure, demography and uptake of prevention strategies. AB - Virtual elimination of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is a global target. A review of the literature was conducted using medical databases and health department websites to examine the current trends related to perinatal HIV exposure and MTCT in Australia in comparison with other high-income countries (HICs). The review discusses the uptake of prevention strategies and barriers that impede MTCT prevention. The literature suggests an increase in the numbers of HIV-exposed deliveries, but a marked decline in the rates of MTCT within HICs. MTCT remains high when the mother's HIV infection is diagnosed late or postpartum. Data supports increasing trends of perinatal HIV exposure in migrant populations from low- and middle income countries (particularly African women). Increased uptake and earlier initiation of antiretroviral therapy (ART) was associated with overall MTCT decline. Caesarean section remains the main mode of delivery described; however, the numbers of planned vaginal deliveries are increasing over time. Heterogeneity of data periods and outcome measures within published literature made comparisons between countries difficult. Future development should focus on clear national guidelines and a potential national database for perinatal HIV, culturally appropriate service provision, and more evidence on acute infections in pregnancy and the effects that longer duration and increased uptake of ART has on the fetus and resistance to ART. PMID- 29787623 TI - Paediatric mastocytosis: long-term follow-up of 53 patients with whole sequencing of KIT. A prospective study. AB - BACKGROUND: Mastocytosis is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells. The adult and paediatric forms differ in their clinical and genetic features and outcomes. OBJECTIVES: To describe the clinical evolution of a well-characterized cohort of paediatric mastocytosis (PM), and to analyse the relationship between KIT mutation and the clinical course. METHODS: This was a prospective cohort study performed at the National Clinical Reference Center for Mastocytosis. Diagnosis was confirmed by identification of KIT mutation on lesional skin biopsy. Mastocytosis subtype, mast cell mediator-related symptoms (MC MRS) and clinical course were recorded. Fifty-three patients with PM and > 4 years of disease course were enrolled. The mean +/- SD age at the final evaluation was 13.2 +/- 4.8 years. The main outcome was the type of KIT mutation as a predictor of evolution and clinical characteristics. RESULTS: Patients presented with maculopapular cutaneous mastocytosis (n = 44), diffuse cutaneous mastocytosis (n = 6) or mastocytoma (n = 3). The mean duration of disease was 12.1 years. Substantial or partial cutaneous regression (18 of 53 and 16 of 53), stabilization or aggravation (16 of 53) and complete cutaneous regression (three of 53) were noted. MC MRS mainly regressed (21 of 53). For 22 patients, evolution of MC MRS and evolution of cutaneous lesions were different. No significant association between evolution and KIT mutation or between evolution and type of cutaneous mastocytosis was found. A late onset of the disease (after 2 years) is associated with worse evolution. CONCLUSIONS: PM is not systematically self regressive. MC MRS manifestations and cutaneous lesions can persist or increase overtime. KIT mutation is not a predictor of evolution. PMID- 29787625 TI - A bald statement - Current approaches to manipulate miniaturisation focus only on promoting hair growth. AB - Hair plays a large part in communication and society with its role changing through time and across cultures. Most people do not leave the house before combing their hair or shaving their beard and for many hair loss or irregular hair growth can have a significant impact on their psychological health. Somewhat unsurprisingly, according to GMR Data, today's global hair care industry is worth an estimated $87 Billion, with hair loss estimated at $2.8 Billion. Considering that no current hair loss-related products can completely reverse hair loss, it is reasonable to believe this market could expand significantly with the discovery of a comprehensive therapy. As such, a great deal of research focuses on overcoming hair loss, and in particular, a common form of hair loss known as androgenetic alopecia (AGA) or male pattern baldness. In AGA, hair follicles miniaturise in a large step change from a terminal to a vellus state. Within this viewpoint article, we discuss how influx and efflux of cells into and out from the dermal papilla (DP) can modulate DP size during the hair cycle. As DP size is positively correlated with the size of the hair fibre produced by a follicle, we argue here that therapies for treating AGA should be developed which can alter DP size, rather than just promote hair growth. We also discuss current therapeutics for AGA and emphasise the importance of using the right model systems to analyse miniaturisation. PMID- 29787624 TI - Anaphylaxis admissions to pediatric intensive care units in France. PMID- 29787627 TI - Hydroxylamine Derivatives as Nitrogen-Radical Precursors in Visible-Light Photochemistry. AB - In recent years, hydroxylamines derivatives have been exploited as nitrogen radical precursors in visible-light photochemistry. Their ability to serve as electrophores in redox chemistry has propelled the development of many novel transformations. Fundamental mechanistic aspects as well as the importance in the preparation of nitrogen-containing molecules will be highlighted. PMID- 29787626 TI - Organotin Selenide Clusters and Hybrid Capsules. AB - Several compounds with unique structural motifs that have already been known from organotin sulfide chemistry, but remained unprecedented in organotin selenide chemistry so far, have been synthesized. The reaction of [(R1 Sn)4 Se6 ] (R1 =CMe2 CH2 C(O)Me) with N2 H4 ?H2 O/(SiMe3 )2 Se and PhN2 H3 /(SiMe3 )2 Se led to the formation of [{(R2 Sn)2 SnSe4 }2 (MU-Se)2 ] (1; R2 =CMe2 CH2 C(Me)NNH2 ) and [{(R3 Sn)2 SnSe4 }2 (MU-Se)2 ] (2; R3 =CMe2 CH2 C(Me)NNPhH)). The addition of ortho-phthalaldehyde to [(R2 Sn)4 Se6 ] yielded a cluster with intramolecular bridging of the organic groups, namely, [(R4 Sn2 )2 Se6 ] (3; R4 =(CMe2 CH2 C(Me)NNCH)2 C6 H4 ). The introduction of organic ligands with longer chains finally allowed the isolation of inorganic-organic capsules of the type [(MU-R)3 (Sn3 Se4 )2 ]X2 , with R=(CMe2 CH2 C(Me)NNHC(O))2 (CH2 )4 and X=[SnC3 ], Cl (4 a, b) or R=CMe2 CH2 C(Me)NNH)2 and X=[SnCl3 ] (5). The capsules enclose solvent molecules and/or anions as guests. All compounds were characterized by means of single-crystal X-ray diffraction studies, NMR spectroscopy, and mass spectrometry. PMID- 29787628 TI - Simultaneous Stabilization of Potassium Metal and Superoxide in K-O2 Batteries on the Basis of Electrolyte Reactivity. AB - In superoxide batteries based on O2 /O2- redox chemistry, identifying an electrolyte to stabilize both the alkali metal and its superoxide remains challenging owing to their reactivity towards the electrolyte components. Bis(fluorosulfonyl)imide (FSI- ) has been recognized as a "magic anion" for passivating alkali metals. The KFSI-dimethoxyethane electrolyte passivates the potassium metal anode by cleavage of S-F bonds and the formation of a KF-rich solid-electrolyte interphase (SEI). However, the KFSI salt is chemically unstable owing to nucleophilic attack by superoxide and/or hydroxide species. On the other hand, potassium bis(trifluorosulfonyl)imide (KTFSI) is stable to KO2 , but results in mossy potassium deposits and irreversible plating and stripping. To circumvent this dilemma, we developed an artificial SEI for the metal anode and thus long-cycle-life K-O2 batteries. This study will guide the development of stable electrolytes and artificial SEIs for metal-O2 batteries. PMID- 29787629 TI - Thermally Twistable, Photobendable, Elastically Deformable, and Self-Healable Soft Crystals. AB - The first example of a smart crystalline material, the 2:1 cocrystal of probenecid and 4,4'-azopyridine, which responds reversibly to multiple external stimuli (heat, UV light, and mechanical pressure) by twisting, bending, and elastic deformation without fracture is reported. This material is also able to self-heal on heating and cooling, thereby overcoming the main setbacks of molecular crystals for future applications as crystal actuators. The photo- and thermomechanical effects and self-healing capabilities of the material are rooted in reversible trans-cis isomerization of the azopyridine unit and crystal-to crystal phase transition. Fairly isotropic intermolecular interactions and interlocked crisscrossed molecular packing secure high elasticity of the crystals. PMID- 29787630 TI - People with dementia getting lost in Australia: Dementia-related missing person reports in the media. AB - OBJECTIVE: This study aimed to understand the circumstances in which people with dementia become lost, and the outcomes of these incidents. METHODS: A search was conducted of news articles published in Australia between 2011 and 2015 reporting a missing person with a diagnosis of dementia. RESULTS: Over the five-year period, 130 missing person cases were reported. The average age of the missing person was 75 years with more men (74%) than women reported missing. Most missing persons travelled on foot (62%) and were last seen at home (66%). The newspaper reports described 92 (71%) of the individuals being found. Of these, 60% were found well, 20% were found injured, and 20% were deceased. CONCLUSIONS: People with dementia are at risk of becoming lost from their homes or health-care settings, and this can have catastrophic outcomes. Care strategies need to focus on promoting autonomy while ensuring adverse outcomes are minimised. PMID- 29787631 TI - Tooth Loss and Dental Implant Outcomes-Where is dentistry going? A Survey by SIdP, the Italian Society of Periodontology and Implantology. PMID- 29787632 TI - Peri-implant soft tissue status and crestal bone levels around adjacent implants placed in patients with and without type-2 diabetes mellitus: 6 years follow-up results. AB - BACKGROUND: The long-term success and survival of dental implants type-2 diabetic subjects is debatable. PURPOSE: The present 6 years' follow-up prospective clinical study compared the peri-implant soft tissue status and crestal bone loss (CBL) around adjacent implants placed among type-2 diabetic and nondiabetic subjects. MATERIALS AND METHODS: Type-2 diabetic (Group-1) and nondiabetic individuals (Group-2) with adjacent dental implants were included. Hemoglobin A1c (HbA1c) levels were recorded; and a questionnaire was used to collect demographic information. Information regarding implant dimensions, duration in function, loading protocol, and type of restoration was recorded. Peri-implant bleeding-on probing (BOP), plaque index (PI), probing depth (PD), and mesial and distal CBL were measured. P < .05 were considered statistically significant. RESULTS: Eighty six male participants (44 in Group-1 and 42 in Group-2) were included. The mean age of individuals in groups 1 and 2 were 57.6 +/- 5.5 and 61.6 +/- 4.3 years, respectively. In Group-1, the mean duration of type-2 diabetes was 10.1 +/- 3.5 years. A family history of diabetes was more often reported by individuals in Group-1 than Group-2. In groups 1 and 2, 44 and 42 pairs of adjacent implants, respectively were placed in the regions of missing premolars and molars in both arches. All implants were delayed loaded and were fixed with non-splinted screw retained restorations. In groups 1 and 2, tooth-brushing twice daily was reported by 79.5% and 85.7% individuals, respectively. There was no difference in peri implant PI, BOP, PD, mesial and distal CBL and HbA1c levels among individuals in groups 1 and 2. CONCLUSION: Adjacent implants can remain esthetically and functionally stable in type 2 diabetic patients in a manner similar to healthy individuals provided glycemic levels are strictly controlled and maintained. PMID- 29787633 TI - Mass Spectrometry Imaging with Isomeric Resolution Enabled by Ozone-Induced Dissociation. AB - Mass spectrometry imaging (MSI) enables the spatial distributions of molecules possessing different mass-to-charge ratios to be mapped within complex environments revealing regional changes at the molecular level. Even at high mass resolving power, however, these images often reflect the summed distribution of multiple isomeric molecules, each potentially possessing a unique distribution coinciding with distinct biological function(s) and metabolic origin. Herein, this chemical ambiguity is addressed through an innovative combination of ozone induced dissociation reactions with MSI, enabling the differential imaging of isomeric lipid molecules directly from biological tissues. For the first time, we demonstrate both double bond- and sn-positional isomeric lipids exhibit distinct spatial locations within tissue. This MSI approach enables researchers to unravel local lipid molecular complexity based on both exact elemental composition and isomeric structure directly from tissues. PMID- 29787634 TI - Confined Ultrathin Pd-Ce Nanowires with Outstanding Moisture and SO2 Tolerance in Methane Combustion. AB - An efficient strategy (enhanced metal oxide interaction and core-shell confinement to inhibit the sintering of noble metal) is presented confined ultrathin Pd-CeOx nanowire (2.4 nm) catalysts for methane combustion, which enable CH4 total oxidation at a low temperature of 350 degrees C, much lower than that of a commercial Pd/Al2 O3 catalyst (425 degrees C). Importantly, unexpected stability was observed even under harsh conditions (800 degrees C, water vapor, and SO2 ), owing to the confinement and shielding effect of the porous silica shell together with the promotion of CeO2 . Pd-CeOx solid solution nanowires (Pd-Ce NW) as cores and porous silica as shells (Pd-CeNW@SiO2 ) were rationally prepared by a facile and direct self-assembly strategy for the first time. This strategy is expected to inspire more active and stable catalysts for use under severe conditions (vehicle emissions control, reforming, and water-gas shift reaction). PMID- 29787635 TI - Abnormal bone remodelling activity of dental follicle cells from a cleidocranial dysplasia patient. AB - OBJECTIVES: To explore the role of dental follicle cells (DFCs) with a novel cleidocranial dysplasia (CCD) causative gene RUNX2 mutation (DFCsRUNX2+/m ) in delayed permanent tooth eruption. MATERIALS AND METHODS: A CCD patient with typical clinical features was involved in this study. DFCsRUNX2+/m were cultured and DNA was extracted for RUNX2 mutation screening. Measurements of cell proliferation, alkaline phosphatase (ALP) activity, alizarin red staining and osteoblast-specific genes expression were performed to assess osteogenesis of DFCsRUNX2+/m . Co-culture of DFCs and peripheral blood mononuclear cells (PBMCs), followed tartrate-resistant acid phosphatase (TRAP) staining, real-time PCR and western blot were performed to evaluate osteoclast-inductive capacity of DFCsRUNX2+/m . RESULTS: A missense RUNX2 mutation (c. 557G>C) was found in DFCsRUNX2+/m from the CCD patient. Compared with normal controls, this mutation did not affect the proliferation of DFCsRUNX2+/m , but down-regulated the expression of osteogenesis-related genes, leading to a decrease in ALP activity and mineralisation. Co-culture results showed that DFCsRUNX2+/m reduced the formation of TRAP+ multinucleated cells and the expression of osteoclastogenesis associated genes. Furthermore, the mutation reduced the ratio of RANKL/OPG in DFCsRUNX2+/m . CONCLUSIONS: DFCsRUNX2+/m disturbs bone remodelling activity during tooth eruption through RANK/RANKL/OPG signalling pathway and may thus be responsible for impaired permanent tooth eruption in CCD patients. PMID- 29787636 TI - An Objective Alternative to IUPAC's Approach To Assign Oxidation States. AB - The IUPAC has recently clarified the term oxidation state (OS), and provided algorithms for its determination based on the ionic approximation (IA) of the bonds supported by atomic electronegativities (EN). Unfortunately, there are a number of exceptions and ambiguities in IUPAC's algorithms when it comes to practical applications. Our comprehensive study reveals the critical role of the chemical environment on establishing the OS, which cannot always be properly predicted using fix atomic EN values. By identifying what we define here as subsystems of enhanced stability within the molecular system, the OS can be safely assigned in many cases without invoking exceptions. New insights about the effect of local aromaticity upon OS are revealed. Moreover, we prove that there are intrinsic limitations of the IA that cannot be overcome. In this context, the effective oxidation state (EOS) analysis arises as a robust and general scheme to derive an OS without any external guidance. PMID- 29787638 TI - Incidence, trends and severity of primary postpartum haemorrhage in Australia: A population-based study using Victorian Perinatal Data Collection data for 764 244 births. AB - BACKGROUND: Increasing incidence and severity of postpartum haemorrhage, together with postpartum haemorrhage-associated morbidities, have been reported in many high-resource countries. In-depth analysis of such factors in Victorian births since 2002 was lacking. AIMS: Our aim was to determine the incidence and trends for primary postpartum haemorrhage (World Health Organization and International Classification of Diseases 10th revision, Australian Modification definitions) for all confinements in Victoria, Australia, for the years 2003-2013 and the incidence and trends for severe postpartum haemorrhage (>=1500 mL) for 2009-2013. MATERIALS AND METHODS: In this population-based cross-sectional study de identified data from the Victorian Perinatal Data Collection were analysed for confinements (excluding terminations) from 2003 to 2013 (n = 764 244). Perinatal information for all births >=20 weeks (or of at least 400 g birthweight if gestation was unknown) were prospectively collected. RESULTS: One in five women (21.8%) who gave birth between 2009 and 2013 experienced a primary postpartum haemorrhage and one in 71 women (1.4%) experienced a severe primary postpartum haemorrhage. The increasing trends in incidence of primary postpartum haemorrhage, severe primary postpartum haemorrhage, blood transfusion, admission to an intensive care or high dependency unit and peripartum hysterectomy were significant (P < 0.001). Women who had an unassisted vaginal birth had the lowest incidence of primary postpartum haemorrhage. The highest incidence was experienced by women who had an unplanned caesarean section birth. Women who had a forceps birth had the highest incidence of severe primary postpartum haemorrhage. CONCLUSIONS: The incidence of primary postpartum haemorrhage, severe primary postpartum haemorrhage and associated maternal morbidities have increased significantly over time in Victoria. PMID- 29787637 TI - Fear-based niche shifts in neotropical birds. AB - Predation is a strong ecological force that shapes animal communities through natural selection. Recent studies have shown the cascading effects of predation risk on ecosystems through changes in prey behavior. Minimizing predation risk may explain why multiple prey species associate together in space and time. For example, mixed-species flocks that have been widely documented from forest systems, often include birds that eavesdrop on sentinel species (alarm calling heterospecifics). Sentinel species may be pivotal in (1) allowing flocking species to forage in open areas within forests that otherwise incur high predation risk, and (2) influencing flock occurrence (the amount of time species spend with a flock). To test this, we conducted a short-term removal experiment in an Amazonian lowland rainforest to test whether flock habitat use and flock occurrence was influenced by sentinel presence. Antshrikes (genus Thamnomanes) act as sentinels in Amazonian mixed-species flocks by providing alarm calls widely used by other flock members. The alarm calls provide threat information about ambush predators such as hawks and falcons which attack in flight. We quantified home range behavior, the forest vegetation profile used by flocks, and the proportion occurrence of other flocking species, both before and after removal of antshrikes from flocks. We found that when sentinel species were removed, (1) flock members shifted habitat use to lower risk habitats with greater vegetation cover, and (2) species flock occurrence decreased. We conclude that eavesdropping on sentinel species may allow other species to expand their realized niche by allowing them to safely forage in high-risk habitats within the forest. In allowing species to use extended parts of the forest, sentinel species may influence overall biodiversity across a diverse landscape. PMID- 29787640 TI - Elevated levels of 8-OHdG and PARK7/DJ-1 in peri-implantitis mucosa. AB - BACKGROUND: Reactive oxygen species contribute to periodontal tissue homeostasis under control of anti-oxidative responses. Disruption in this balance induces severe inflammation and extended tissue degradation. PURPOSE: Aim of this study was to identify the expression levels of nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2), Parkinsonism associated deglycase (PARK7/DJ-1), kelch-like ECH associated protein 1 (KEAP1), and 8-hydroxy-deoxyguanosine (8-OHdG) in peri implant mucosal tissues affected by peri-implantitis, and to compare the levels to those of periodontally diseased and healthy tissue samples. METHODS: Tissue biopsies were collected from systemically healthy, non-smoking 12 peri implantitis patients, 13 periodontitis patients, and 13 periodontally healthy controls. Expression levels of NFE2L2/NRF2, PARK7/DJ-1, KEAP1, and 8-OHdG in tissue samples were analyzed immunohistochemically. Statistical analysis was performed by one-way ANOVA with Tukey's HSD test. RESULTS: Inflammatory cell infiltration in the connective tissue and loss of architecture in the spinous layer of the epithelium were prominent in peri-implantitis. Proportions of 8-OHdG and PARK7/DJ-1 expressing cells were elevated in both peri-implantitis (P = .025 for 8-OHdG and P = .014 for PARK7/DJ-1) and periodontitis (P = .038 for 8-OHdG and P = .012 for PARK7/DJ-1) groups in comparison with controls. Staining intensities of 8-OHdG and PARK7/DJ-1 were higher in the periodontitis and peri implantitis groups than in the control (P < .01) groups. There was no difference in the expression levels of NFE2L2/NRF2 between the groups. KEAP1 was not observed in any tissue sample. CONCLUSIONS: Peri-implantitis is characterized by severe inflammation and architectural changes in the epithelium and connective tissue. The expressions of 8-OHdG and PARK7/DJ-1 are elevated in both peri implantitis and periodontitis. PMID- 29787639 TI - Detergent-assisted sample preparation for MALDI-MS: Investigation of octylglucoside and docecylmaltoside for matrix crystallization, on-plate digestion, and trypsin activity. AB - We show an easy and fast method for improved detection of lipophilic peptides with MALDI-MS utilizing the nonionic detergents n-octylglucoside and n dodecylmaltoside (laurylmaltoside). Investigations comprised on-plate digestion of proteins with trypsin, detergent effects on the protease trypsin, and the changes in MALDI matrix crystallization. Investigations also exhibited a higher tryptic activity in trypsin activity assay of 139% when using laurylmaltoside as supplement. Crystallization changed toward a more homogeneous crystal distribution and especially trypsinized insulin spectra recorded with MALDI-MS showed improved detectability of lipophilic peptides. PMID- 29787642 TI - New Initiative Slashes Opioid Prescriptions, Boosts Community Response. AB - The Community Hospital of Monterey Peninsula (CHOMP) has spearheaded a multiagency collaborative that has been successful at more than halving the prescriptions for narcotics in the region and trimming ED visits among frequent users. Known as "Prescribe Safe," the approach can be credited, in part, with nudging emergency providers to view addiction as a disease and to reevaluate their role in linking patients with needed treatment. Under its recurrent visitors program, emergency providers at CHOMP reject the term "drug seeking," instead focusing on addressing the underlying reasons for a patient's addiction problem. A centerpiece of the Prescribe Safe initiative is county-wide implementation of pain management protocols for the ED, coupled with provider and patient education initiatives about these guidelines and why they are important. Physician leaders of the Prescribe Safe initiative note that networking with community partners has produced alliances with law enforcement on drug take back events and a more effective response to drug diversion and prescription forgery. By making safety the ultimate goal of the initiative, patient provider conflict over prescribing choices has been minimized. PMID- 29787641 TI - Effect of implant therapy on oral health-related quality of life (OHIP-49), health status (SF-36), and satisfaction of patients with several agenetic teeth: Prospective cohort study. AB - BACKGROUND: Effect of fixed prosthodontics on patients with several agenetic teeth is not well understood. PURPOSE: To assess the effect of implant-based fixed prosthodontics on oral health-related quality of life (OHRQoL), general health status, and satisfaction regarding dental appearance, ability to chew and speech in patients with several agenetic teeth. MATERIALS AND METHODS: For this prospective cohort study, all patients (>=18 years) with several agenetic teeth who were scheduled for treatment with fixed dental implants between September 2013 and July 2015 at our department were approached. Participants received a set of questionnaires before and 1 year after implant placement to assess OHRQoL (OHIP-NL49), general health status (SF-36), and satisfaction regarding dental appearance, ability to chew and speech. RESULTS: About 25 out of 31 eligible patients (10 male, 15 female; median age: 20 [19;23] years; agenetic teeth: 7 [5;10]) were willing to participate. Pre- and post-treatment OHIP-NL49 sum-scores were 38 [28;56] and 17 [7;29], respectively (P < .001). Scores of all OHIP-NL49 subdomains decreased tool, representing an improved OHRQoL (P < .05) as well as that satisfaction regarding dental appearance, ability to chew and speech increased (P < .001). General health status did not change with implant treatment (P > .05). CONCLUSIONS: Treatment with implant-based fixed prosthodontics improves OHRQoL and satisfaction with dental appearance, ability to chew and speech, while not affecting general health status. PMID- 29787643 TI - A Second Look at ED-initiated Buprenorphine for Opioid Addiction. PMID- 29787644 TI - Guide Patients into Treatment Through Outreach Visits. AB - By working with the police department and area addiction treatment centers, Beth Israel Deaconess Hospital in Plymouth, MA, (BID-Plymouth) has been able to persuade many more patients who present to the ED with addiction problems to seek needed treatment. The approach involves the creation of an outreach team that visits patients in their homes within a day of discharge from the hospital following an overdose. A behavioral health team embedded in the ED sees all patients who pres- ent to the ED with addiction issues. While the vast majority of these patients reject addiction treatment alternatives at this stage, administrators have found patients to be much more amenable to accepting treatment once patients have returned home. In the first nine months of the program, roughly 80% of patients with addic- tion problems agreed to seek treatment following an outreach visit. A police officer always accompanies clinicians on outreach visits and can help the team work around confidentiality issues. Emergency providers at BID-Plymouth have devised opioid guidelines to ensure prescriptions are used only when appropriate. By sharing information with providers about how their own prescribing practices compare with the prescribing practices of their peers, administrators have produced significant declines in opioid prescribing. PMID- 29787645 TI - Warm Handoffs Connect Substance Abuse Patients to Vital Services. PMID- 29787646 TI - Doing the right thing: moral distress and disclosure of health information. PMID- 29787647 TI - Preventing infection: guidelines for hand hygiene. PMID- 29787648 TI - Alberta: Home of great nursing leaders. PMID- 29787649 TI - THE palliative APPROACH. AB - DEATH. It's not an easy thing to think about. People are often reluctant to consider their own mortality. However, death and dying are a fact of life. The fact that end-of-life care will be required for the vast majority of the population isn't something we often consider - unless you are a palliative care consultant or another health professional working in palliative care. We face death on a daily basis. Palliative care is an approach to health care that aims to relieve suffering and improve the quality of both living and dying. We, palliative care consultants, endeavour to help patients deal with important physical, psychological, social, spiritual, and practical issues as they prepare for dying. We also help their loved ones cope with loss and grief after death has occurred. PMID- 29787650 TI - PART FOUR OF FOUR: A History of Nursing - Current era: 1990 to present. PMID- 29787651 TI - The Night Dallas Seemed More Like Afghanistan. AB - Just one month after a mass shooting in Orlando, FL, emergency providers in Dallas were challenged to respond to another incident of gun violence. In this case, a sniper opened fire on a peaceful protest, hitting 14 people, including five police officers who died from their wounds. Emergency and trauma personnel from Parkland Memorial Hospital and Baylor University Medical Center report that their teams performed well, but having worked side-by-side with law enforcement many times, many providers and emergency staff are dealing with a heavy dose of emotional distress. With no notice, victims of the shooting began arriving at Baylor University Medical Center in police cars. Emergency personnel noted that some of the vehicles themselves were riddled with bullet holes. At Parkland Memorial Hospital, trauma staff immediately activated their incident command to a "code yellow, level three," meaning there were multiple casualties. Not knowing how many shooters there were, the hospital also activated security, using its own 100-person police force to patrol the hospital's perimeter. Before the night was over, Parkland treated seven patients from the mass shooting--all of them police officers. But the 108-bed ED also had many other cases to manage that were not related to the mass shooting incident. This incident illustrates the importance of including the chaplains of police and fire departments as well as the hospital when preparing and drilling for mass-casualty events, and putting resources in place to help emergency staff deal with distress. PMID- 29787652 TI - Best Practices, Investments Needed to Communicate Effectively with LEP Patients. AB - Resource-challenged hospitals have long struggled to meet the needs of patients with limited English proficiency (LEP), often relying on ad hoc interpreters to communicate with these individuals. However, such shortcuts carry risks, and with the increasing diversity of the population, there is a new push by the Department of Health and Human Services' Office of Civil Rights and other organizations for hospitals to make the investments needed to ensure effective communications between providers and LEP patients. Experts note that many hospitals across the country lack a basic foundation for communicating with LEP patients. Many hospitals with dedicated interpreter services haven't built the systems or trained staff to use these services effectively. Experts advise ED providers to collect and track English proficiency data on all patients, and provide trained medical interpreters to all LEP patients and families. Printed materials, such as discharge instructions and prescriptions, also must be translated into a patient's native language, and these materials must be reviewed with the patient with the help of a translator. PMID- 29787653 TI - Tragedies Provide Learning Opportunities. AB - With the increasing frequency of mass-casualty events, the American College of Emergency Physicians has assembled a High Threat Task Force to look for ways to improve the emergency response to these events. The panel intends to focus on training and operations, but the ultimate goal is to find ways to eliminate preventable deaths. The panel intends to standardize and unify improvement efforts that have thus far been disparate. The co-chairman of the panel says one of the biggest gaps is the lack of evidence-based guidelines for how emergency personnel should respond to mass-shooting events. Noting that the incident command structure was created for fighting wildfires, the co-chairman of the task force notes that mass-shooting events require a more dynamic leadership response. PMID- 29787654 TI - Optimal Teams and Performance Feedback Drive Improvements in Processing Measures. AB - The ED at ProMedica Toledo Hospital, a Level I trauma facility in Toledo, OH, has been able to chart impressive metrics on patient processing measures year after year. Administrators credit an overhaul in their triage process, a comprehensive approach to providing staff with regular feedback on their performance, and a system that relies on optimally sized teams to deliver care. Department leaders are hoping to boost patient satisfaction scores with an initiative that will leverage champions, fresh metrics, and a new mission statement to highlight the importance of the patient experience. Hospital administrators report that the median door-to-bed time in the ED is 23 minutes, and the median bed-to-physician time is eight minutes. The median length of stay for all ED patients stands at 121 minutes, and hospital administrators note that the ED's leave-without-being seen rate tends to hover beneath 1%, far below the naticnal average. The ED uses a zone system that can adjust from two to five zones, depending on patient volume. The charge nurse is responsible for assigning patients to specific zones for care. PMID- 29787655 TI - NURSING PRACTICE Higher education Learning what it means to provide spiritual care. PMID- 29787656 TI - PROFESSIONAL-DEVELOPMENT Frontline change Building the next generation of leaders, problem-solvers and innovators. PMID- 29787657 TI - NURSING PRACTICE AND WORK ENVIRONMENT Gaining momentum: Collaboration for academic progression. PMID- 29787658 TI - PRACTICE Preventing tragedies New Mexico nurses lead initiative on shaken baby syndrome. PMID- 29787660 TI - Prevent Mental Health Problems from Escalating into Crises. PMID- 29787659 TI - Novel Paramedic Programs Respond to Behavioral Health-related Calls. AB - A number of communities are turning to community paramedicine programs to help manage the crushing demand on EDs and EMS providers by patients with behavioral health (BH) concerns. In Modesto, CA, a pilot program provides extra training to paramedics to respond to BH-related calls, and a program in Atlanta pairs paramedics with mental health social workers to meet the needs of BH patients, many of whom repeatedly call 911 for help. Both programs curb the need for hospital and ED visits while linking patients with appropriate care more expeditiously. However, a shortage of psychiatric treatment facilities remains a barrier. Paramedics in the Modesto, CA, program undergo 140 hours of specialized training in how to handle BH related 911 calls safely and appropriately. Program developers note that most of these patients can be stabilized within 23 hours, nixing the need for a bed in an inpatient psychiatric facility. Developers say that the pilot program has saved more than $1 million and significantly reduced the time to treatment for BH patients. The Upstream Crisis Intervention program in Atlanta teams a paramedic with a mental health social worker to respond to BH related calls through a mental health unit that is dispatched through the 911 system. The mental health unit teams also check on BH patients when they are not in crisis to make sure they have their medicine and are on track with their plan of care; the teams will intervene if patients need assistance. PMID- 29787661 TI - Administrators Leverage Predictive Analytics to Manage Capacity, Streamline Decision-making. AB - A growing number of hospitals are turning to predictive analytics to anticipate and manage volume better. The approach, which involves using sophisticated simulation and modeling techniques, enables administrators to get ahead of patient surges and to focus on pressure points. For example, Johns Hopkins Hospital in Baltimore has made significant progress on a range of measures, using a centralized command center to monitor the hospital's data streams. The approach enables the hospital to accelerate decision-making and optimize hospital resources. Investigators at Columbia University believe similar modeling techniques can be used to avert ED congestion when used in conjunction with proactive diversion strategies. The 5,000-square-foot command center at Johns Hopkins Hospital monitors 14 IT systems on a 24/7 basis so that all relevant inputs can factor into decision-making about beds, transfers, consults, admissions, discharges, and other aspects of care. Administrators say they have been able to achieve 96% accuracy in their predictions. In just 10 months of operation, the data-driven command center has achieved dramatic improvements, including a 30% reduction in the number of emergency patients who must wait for an inpatient bed and a one-hour reduction in the time it takes to get out the door to retrieve a patient identified for transfer to the Hopkins facility. In addition, the hospital has all but eliminated procedure cancellations due to OR holds. Investigators at Columbia University contend that by using predictive analytics to guide proactive diversion strategies, ED delays can be reduced by as much as 15%. PMID- 29787662 TI - New Mobile Stroke Unit Programs Aim to Improve Outcomes. AB - Now well-established throughout Europe, mobile stroke unit (MSU) programs are in the early stages of development in the United States. The concept aims to improve outcomes by bringing diagnostic capabilities and clot-busting care to the patients experiencing stroke, thereby reducing the time to treatment. In October, New York Presbyterian/Weill Cornell Medical Center in New York became the first medical center on the East Coast to deploy an MSU, and in July, the University of Tennessee College of Medicine in Memphis deployed a first-of-its-kind MSU that is larger and more robust than other MSUs currently in use. In the first month of operation, the MSU in New York responded to 29 calls and brought 12 patients to the hospital with suspected strokes. Two of these patients received tissue plasminogen activator in the field and both made full recoveries by the next day. The MSU deployed in Memphis is larger and carries more sophisticated diagnostic equipment than other MSUs. The program also replies on doctorally prepared, vascular neurology fellowship-trained nurse practitioners, instead of relying on telemedicine connections to external experts. Now operating with the assistance of grant funding, leaders of both programs hope that strong outcomes will prove convincing to hospitals and prayers, although the U.S. healthcare model complicates the establishment of a reimbursement structure for MSUs. PMID- 29787663 TI - Combined Pediatric ED/Inpatient Unit Concept Catches On with Maryland Community Hospitals. AB - Some community hospitals that struggle to maintain a financially viable pediatric inpatient service have found success with a model that combines their pediatric inpatient unit with a pediatric ED. The approach was developed first at Howard County General Hospital in Columbia, MD, nearly two decades ago, and has been duplicated at other community hospitals in the state. Now, community hospitals elsewhere are taking a look. In addition to the financial benefits, users of this approach say that it can improve throughput while also boosting patient and provider satisfaction. The concept involves placing the pediatric inpatient unit adjacent to the pediatric ED so that pediatric physicians and nurses can float between the two sides of the unit as needed, maximizing resources. Although the approach initially takes volume away from the adult ED, administrators say hospitals generally replace this volume within two years. Pioneers of the combined model note community hospitals must engage in at least 10,000-12,000 pediatric encounters in the ED every year for the combined pediatric inpatient unit/pediatric ED model to be successful. PMID- 29787664 TI - [COMPARISON OF PHARMACOLOGICAL EFFECTS OF HEPTAPEPTIDE SELANK AFTER INTRANASAL AND INTRAPERITONEAL ADMINISTRATION TO BALB/c AND C57BL/6 MICE.] AB - Pharmacological effects of intraperitoneal (i.p.) and intranasal (i.n.) administration of heptapeptide selank (300 MUg/kg/day for 5 days), known to possess anxiolytic and nootropic properties, were compared by studying the elevated-plus-maze behavior of inbred BALB/c and C57BL/6 mice and measuring the binding of markers to NMDA and GABA receptors of brain. The anxiolytic and nootropic efficiency of selank administered via both routes was observed only in BALB/c mice, which were characterized by initially reduced exploratory activity and higher levels of anxiety as compared to C57BL/6 mice. In BALB/c mice, i.p. selank increased the number of [G-(3)H]SR 95531 binding sites with GABA-receptors in the frontal cortex by 38%, without change in binding to NMDA receptors in the hippocampus. On the contrary, i.n. selank led to an increase in the density of [G (3)H]MK-801 binding sites by 23% with no effect on GABA receptors. It is suggested that the differences in pharmacological spectra observed for the two routes of selank administration are determined by specific features of drug pharmacokinetics and biotransformation as well as by the dynamics of formation of the anxiolytic and nootropic effects of selank. PMID- 29787665 TI - [THE INFLUENCE OF NITROGLYCERIN ON SPECTRAL AND OXYGEN-BINDING CHARACTERISTICS OF HUMAN INTRACELLULAR HEMOGLOBIN.] AB - The spectral and oxygen-binding characteristics of human intracellular hemoglobin in the presence of nitroglycerin at concentrations of 5 ng/mL and 5 MUg/mL have been studied. Short incubation (20 min) of erythrocytes with the drug led increasing hemoglobin affinity to oxygen and weakening of cooperative interactions in hemoprotein molecules. As a result, the amount of O(2) supplied to tissues in the process of gas exchange decreased by 23.96% (5 ng/mL) and 26.68% (5 MUg/ml), p < 0.05. Incubation of cells for 24 h resulted in oxidation of the heme iron atom, accumulation of methemoglobin, and partial hemolysis. Nitroglycerin reduces the intensity of oxidative processes. However, no dependence of the degree of changes in the physical and chemical properties of hemoglobin on the concentration of nitroglycerin was found. PMID- 29787666 TI - [POLYMORPHISM OF CYP2C9 GENE AND RISK OF HEPATOTOXICITY DEVELOPMENT DURING ANTIRETROVIRAL THERAPY.] AB - We have studied the association of polymorphic variants of CYP2C9 genes with the risk of drug-induced liver injury (DILI) during antiretroviral therapy of HIV infected patients. The analysis of polymorphic variants of CYP2C9*2.(Argl44Cys) and CYP2C9*3 (Ile359Leu) genes showed that the dominant genotype of CYP2C9*2 was the honiozygous CC carriership and for CYP2C9*3 it was the prevalence of AA genotype, the incidence of which was close and amounted to 80%. There was no association of these genotypes CYP2C9 with the risk of DILI. Thus, the carriership of individual C and T alleles in the case of CYP2C9*2 gene, as well as A and C for CYP2C9*3 is not a predictor of antiretroviral DILI. PMID- 29787667 TI - [INFLUENCE OF PROGESTERONE DERIVATIVES ON THE VIABILITY AND EXPRESSION OF ESTROGEN RECEPTOR-ALPHA MRNA IN HELA CELLS.] AB - We have studied the effect of new ligands of progesterone receptors, including pregna-D'-pentaran 6-methoxyimino-16a,17a-cyclohexanopregn-4-en-3,20-dio-ne (K1047), 17a-acetoxy-3b-butanoyloxy-6-methylpregna-4,6-dien-20-one (buterol), progesterone (P4), and medroxyprogesterone acetate on the viability of HeLa cells and expression of estrogen receptor-alpha (Era) mRNA gene in these cells. K1I047 and buterol exhibited high cytostatic activity, which exceeded the activity of reference compounds on the average by 15% (p < 0.05). Both buterol and K-1047 (at 10(-6)M) effectively suppressed ERa mRNA gene expression in HeLa cell culture by 83.4 - 9 8.6%. PMID- 29787668 TI - [INFLUENCE OF A NEW SUBSTANCE WITH ANTIDEPRESSANT ACTIVITY ON ORGANO- AND FETOGENESIS PROCESSES REGISTERED DURING ANTHENATAL PERIOD.] AB - Experiments on pregnant female rats showed that the beta-phenylglutaminic acid hydrochloride derivative neuroglutam (glutaron), exhibiting antidepressant and anxiolytic activity upon intragastric administration in doses of 26, 130 and 650 mg/kg to female rats from 6 to 16 days of pregnancy, does not impair organo- and fetogenesis processes (developments of fetus) registered during the anthenatal period, decreases fetal death, and activates the processes of prenatal development of the fetus bv 11.1% (p < 0.001), 8.3% (p < 0.001), and 2.8% (p < 0.05), respectively. PMID- 29787669 TI - [STRESS-PROTECTIVE EFFECT OF CYTOFLAVIN ON CHRONIC CEREBRAL ISCHEMIA IN RATS.] AB - Analysis of stress-releasing blood reactions (electrophoretic mobility of red blood cells, WBC count, and leukocyte ratio) in rats with experimental cerebral ischernia under the action of cytoflavin held showed that cytoflavin in combination with basic therapy leads to further activation of compensatory adaptive reactions of the body and stimulated peripheral stress-limiting mechanisms. PMID- 29787670 TI - [PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.] AB - Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized. PMID- 29787671 TI - [PROTECTIVE ROLE OF MELATONIN IN ETIOLOGY AND COURSE OF PARKINSON'S DISEASE: EXPERIMENTAL EVIDENCE.] AB - Literature data about participation of melatonin - the main hormone of pineal gland - in the origin and course of Parkinson's disease are reviewed. On the cellular level, melatonin demonstrates neuroprotective activity based on the limitation of oxidative stress, inflammation, and degradation of dopamine in nervous tissue, the attenuation of mitochondrial dysfunction, and the accumulation of alpha-synuclein, which are observed in parkinsonian animals and human patients. Moreover, melatonin is capable of inducing some systemic changes that limit disorganization of circadian rhythm and insomnia. It is suggested that, after extensive placebo controlled and randomized examinations in clinical practice, melatonin may be recommended for complex therapy of Parkinson's disease with obligatory taking into consideration some variable factors. PMID- 29787672 TI - Oxidized Nanocarbons-Tripeptide Supramolecular Hydrogels: Shape Matters! AB - Short peptide hydrogels are attractive biomaterials but typically suffer from limited mechanical properties. Inclusion of other nanomaterials can serve the dual purpose of hydrogel reinforcement and of conferring additional physicochemical properties ( e. g., self-healing, conductivity), as long as they do not hamper peptide self-assembly. In particular, nanocarbons are ideal candidates, and their physicochemical properties have demonstrated great potential in nanocarbon-polymer gel biomaterials for tissue engineering or drug delivery. Recently, increasing interest in supramolecular hydrogels drove research also on their enhancement with nanocarbons. However, little is known on the effect of nanocarbon morphology on the self-assembly of short peptides, which are among the most popular hydrogel building blocks. In this work, three different oxidized nanocarbons ( i. e., carbon nanotube or CNT as 1D material, graphene oxide sheet or GO as 2D material, and carbon nanohorn or CNH as 3D material) were evaluated for their effects on the self-assembly of the unprotected tripeptide Leu-DPhe-DPhe at physiological conditions. Supramolecular hydrogels were obtained in all cases, and viscoelastic properties were clearly affected by the nanocarbons, which increased stiffness and resistance to applied stress. Notably, self-healing behavior was observed only in the case of CNTs. Tripeptide-nanotube interaction was noted already in solution prior to self assembly, with the tripeptide acting as a dispersing agent in phosphate buffer. Experimental and in silico investigation of the interaction between peptide and CNTs suggests that the latter acts as nucleation templates for self-assembly and reassembly. Overall, we provide useful insights for the future design of composite biomaterials with acquired properties. PMID- 29787673 TI - Freeze-Dried Carbon Nanotube Aerogels for High-Frequency Absorber Applications. AB - A novel technique for millimeter wave absorber material embedded in a metal waveguide is proposed. The absorber material is a highly porous carbon nanotube (CNT) aerogel prepared by a freeze-drying technique. CNT aerogel structures are shown to be good absorbers with a low reflection coefficient, less than -12 dB at 95 GHz. The reflection coefficient of the novel absorber is 3-4 times lower than that of commercial absorbers with identical geometry. Samples prepared by freeze drying at -25 degrees C demonstrate resonance behavior, while those prepared at liquid nitrogen temperature (-196 degrees C) exhibit a significant decrease in reflection coefficient, with no resonant behavior. CNT absorbers of identical volume based on wet-phase drying preparation show significantly worse performance than the CNT aerogel absorbers prepared by freeze-drying. Treatment of the freeze dried CNT aerogel with n- and p-dopants (monoethanolamine and iodine vapors, respectively) shows remarkable improvement in the performance of the waveguide embedded absorbers, reducing the reflection coefficient by 2 dB across the band. PMID- 29787674 TI - Single Quantum Dot Tracking Reveals Serotonin Transporter Diffusion Dynamics are Correlated with Cholesterol-Sensitive Threonine 276 Phosphorylation Status in Primary Midbrain Neurons. AB - Serotonin transporter (SERT) terminates serotonin signaling in the brain by enabling rapid clearance of the neurotransmitter. SERT dysfunction has been associated with a variety of psychiatric disorders, including depression, anxiety, and autism. Visualizing SERT behavior at the single molecule level in endogenous systems remains a challenge. In this study, we utilize quantum dot (QD) single particle tracking (SPT) to capture SERT dynamics in primary rat midbrain neurons. Membrane microenvironment, specifically membrane cholesterol, plays a key role in SERT regulation and has been found to affect SERT conformational state. We sought to determine how reduced cholesterol content affects both lateral mobility and phosphorylation of conformationally sensitive threonine 276 (Thr276) in endogenous SERT using two different methods of cholesterol manipulation, statins and methyl-beta-cyclodextrin. Both chronic and acute cholesterol depletion increased SERT lateral diffusion, radial displacement along the membrane, mobile fraction, and Thr276 phosphorylation levels. Overall, this work has provided new insights about endogenous neuronal SERT mobility and its associations with membrane cholesterol and SERT phosphorylation status. PMID- 29787675 TI - Metal-Stabilized Quinoidal Dibenzo[ g, p]chrysene-Fused Bis-dicarbacorrole System. AB - We report here a metal complexation-based strategy that permits access to a highly stable expanded porphyrin-type quinoidal polycyclic aromatic hydrocarbons (PAH). Specifically, double insertion of Pd(II) ions into a dibenzo[ g, p]chrysene-fused bis-dicarbacorrole (bis-H3) gives rise to a bis-metalated species (bis-Pd) that undergoes a facile benzenoid-quinonoid transformation. In contrast to what is true for the corresponding mono-Pd(II) complex, which has organic radical character, well resolved 1H NMR and 19F NMR spectra are seen for bis-Pd. This complex is also electron paramagnetic resonance (EPR) silent over a range of temperatures. On the basis of crystallographic analyses, Raman spectroscopic studies, harmonic oscillator model of aromaticity (HOMA), and nucleus-independent chemical shift (NICS) calculations, we suggest that the dibenzo[ g, p]chrysene bridge in bis-Pd has quinoidal character and that the system as a whole is a closed shell species. As expected for a quinoidal system, bis-Pd is characterized by a lowest energy absorption band that is shifted into the NIR (lambdamax = ca. 1420 nm (epsilon > 1.5 * 105 M-1 cm-1) for bis-Pd vs 780 nm (epsilon < 5.0 * 103 M-1 cm-1) for bis-H3). On the other hand, bis-Pd displays solvent dependent ground state and transient absorption spectral features. Such findings provide support for a zwitterionic resonance contribution to what is a predominantly a quinonoid-type ground state. The use of specific metalation to fine-tune the electronic features of polytopic ligands, as reported here, opens the door to what might be a potentially generalizable approach to the design of quinoidal PAH structures with long wavelength solvatochromic absorption features. PMID- 29787677 TI - Synergistic Exposure of Return-Sludge to Anaerobic Starvation, Sulfide, and Free Ammonia to Suppress Nitrite Oxidizing Bacteria. AB - A key step toward energy-positive sewage treatment is the development of mainstream partial nitritation/anammox, a nitrogen removal technology where aerobic ammonium-oxidizing bacteria (AerAOB) are desired, while nitrite-oxidizing bacteria (NOB) are not. To suppress NOB, a novel return-sludge treatment was investigated. Single and combined effects of sulfide (0-600 mg S L-1), anaerobic starvation (0-8 days), and a free ammonia (FA) shock (30 mg FA-N L-1 for 1 h) were tested for immediate effects and long-term recovery. AerAOB and NOB were inhibited immediately and proportionally by sulfide, with AerAOB better coping with the inhibition, while the short FA shock and anaerobic starvation had minor effects. Combinatory effects inhibited AerAOB and NOB more strongly. A combined treatment of sulfide (150 mg S L-1), 2 days of anaerobic starvation, and FA shock (30 mg FA-N L-1) inhibited AerAOB 14% more strongly compared to sulfide addition alone, while the AerAOB/NOB activity ratio remained constant. Despite no positive change being observed in the immediate-stress response, AerAOB recovered much faster than NOB, with a nitrite accumulation ratio (effluent nitrite on nitrite + nitrate) peak of 50% after 12 days. Studying long-term recovery is therefore crucial for design of an optimal NOB-suppression treatment, while applying combined stressors regularly may lead toward practical implementation. PMID- 29787676 TI - Surface Plasmon Resonance Study of the Binding of PEO-PPO-PEO Triblock Copolymer and PEO Homopolymer to Supported Lipid Bilayers. AB - Poloxamer 188 (P188), a poly(ethylene oxide)- b-poly(propylene oxide)- b poly(ethylene oxide) triblock copolymer, protects cell membranes against various external stresses, whereas poly(ethylene oxide) (PEO; 8600 g/mol) homopolymer lacks protection efficacy. As part of a comprehensive effort to elucidate the protection mechanism, we used surface plasmon resonance (SPR) to obtain direct evidence of binding of the polymers onto supported lipid bilayers. Binding kinetics and coverage of P188 and PEO were examined and compared. Most notably, PEO exhibited membrane association comparable to that of P188, evidenced by comparable association rate constants and coverage. This result highlights the need for additional mechanistic understanding beyond simple membrane association to explain the differential efficacy of P188 in therapeutic applications. PMID- 29787678 TI - Three-Dimensional, Solid-State Mixed Electron-Ion Conductive Framework for Lithium Metal Anode. AB - Solid-state electrolytes (SSEs) have been widely considered as enabling materials for the practical application of lithium metal anodes. However, many problems inhibit the widespread application of solid state batteries, including the growth of lithium dendrites, high interfacial resistance, and the inability to operate at high current density. In this study, we report a three-dimensional (3D) mixed electron/ion conducting framework (3D-MCF) based on a porous-dense-porous trilayer garnet electrolyte structure created via tape casting to facilitate the use of a 3D solid state lithium metal anode. The 3D-MCF was achieved by a conformal coating of carbon nanotubes (CNTs) on the porous garnet structure, creating a composite mixed electron/ion conductor that acts as a 3D host for the lithium metal. The lithium metal was introduced into the 3D-MCF via slow electrochemical deposition, forming a 3D lithium metal anode. The slow lithiation leads to improved contact between the lithium metal anode and garnet electrolyte, resulting in a low resistance of 25 Omega cm2. Additionally, due to the continuous CNT coating and its seamless contact with the garnet we observed highly uniform lithium deposition behavior in the porous garnet structure. With the same local current density, the high surface area of the porous garnet framework leads to a higher overall areal current density for stable lithium deposition. An elevated current density of 1 mA/cm2 based on the geometric area of the cell was demonstrated for continuous lithium cycling in symmetric lithium cells. For battery operation of the trilayer structure, the lithium can be cycled between the 3D-MCF on one side and the cathode infused into the porous structure on the opposite side. The 3D-MCF created by the porous garnet structure and conformal CNT coating provides a promising direction toward new designs in solid state lithium metal batteries. PMID- 29787679 TI - Dynamic Proteome Alteration and Functional Modulation of Human Saliva Induced by Dietary Chemosensory Stimuli. AB - Saliva flow measurements and SDS-PAGE separation of human whole saliva freshly collected after oral stimulation with citric acid (sour), aspartame (sweet), iso alpha-acids (bitter), mono sodium l-glutamate (umami), NaCl (salty), 6-gingerol (pungent), hydroxy-alpha-sanshool (tingling), and hydroxy-beta-sanshool (numbing), followed by tryptic digestion, nano-HPLC-MS/MS, and label-free protein quantitation demonstrated a stimulus- and time-dependent influence of the dietary chemosensates on salivation and the salivary proteome composition. Gene ontology enrichment analysis showed evidence for stimulus-induced alterations of the saliva proteome to boot an efficient molecular defense network of the oral cavity, e.g., 6-gingerol increased salivary lactoperoxidase activity, catalyzing the oxidation of thiocyanate to produce the antimicrobial and antifungal hypothiocyanate, from 0.37 +/- 0.02 to 0.91 +/- 0.05 mU/mL 45 s after stimulation. In comparison, oral citric acid stimulation induced an increase of myeloperoxidase activity, catalyzing the chloride oxidation to generate antimicrobial hypochloride in saliva, from 0.24 +/- 0.04 to 0.70 +/- 0.1 mU/mL as well as an increase of salivary levels of lysozyme, exhibiting antimicrobial activity on Gram-positive bacteria, from 6.0-10 to 100-150 MUg/mL. Finally, microbial growth experiments clearly demonstrated for the first time that the increase of the salivary lysozyme abundance upon oral citric acid stimulation translates into an enhanced biological function, that is an almost complete growth inhibition of the two lysozyme-sensitive Gram-positive bacteria tested. PMID- 29787680 TI - Revision Lingual Frenotomy Improves Patient-Reported Breastfeeding Outcomes: A Prospective Cohort Study. AB - BACKGROUND: Lingual frenotomy improves patient-reported outcome measures, including infant reflux and maternal nipple pain, and prolongs the nursing relationship; however, many mother-infant dyads continue to experience breastfeeding difficulty despite having had a frenotomy. Research aim: The aim of this study was to determine how incomplete release of the tethered lingual frenulum may result in persistent breastfeeding difficulties. METHODS: A one group, observational, prospective cohort study was conducted. The sample consisted of breastfeeding mother-infant (0-9 months of age) dyads ( N = 54) after the mothers self-elected completion lingual frenotomy and/or maxillary labial frenectomy following prior lingual frenotomy performed elsewhere. Participants completed surveys preoperatively, 1-week postoperatively, and 1 month postoperatively consisting of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), Visual Analog Scale (VAS) for nipple pain severity, and the Revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R). RESULTS: Significant postoperative improvements were reported between mean preoperative scores compared with 1-week and 1-month scores of the BSES-SF, F(2) = 41.2, p < .001; the I-GERQ-R, F(2) = 22.7, p < .001; and VAS pain scale, F(2) = 46.1, p < .001. CONCLUSION: We demonstrated that besides nipple pain, measures of infant reflux symptoms and maternal breastfeeding self-confidence can improve following full release of the lingual frenulum. Additionally, a patient population was identified that could benefit from increased scrutiny of infant tongue function when initial frenotomy fails to improve breastfeeding symptoms. PMID- 29787681 TI - Higher anthocyanin accumulation associated with higher transcription levels of anthocyanin biosynthesis genes in spinach. AB - Spinach (Spinacia oleracea L.) is widely cultivated as an economically important green leafy vegetable crop for fresh and processing consumption. The red-purple spinach shows abundant anthocyanin accumulation in the leaf and leaf petiole. However, the molecular mechanisms of anthocyanin synthesis in this species are still undetermined. In the present study, we investigated pigment formation and identified anthocyanin biosynthetic genes in spinach. We also analyzed the expression of these genes in purple and green cultivars by quantitative PCR. The accumulation of anthocyanin showed that it was the dominant pigment resulting in the red coloration in spinach. In total, 22 biosynthesis genes and 25 regulatory genes were identified in spinach, based on the spinach genomic and transcriptomic database. Furthermore, the expression patterns of genes encoding enzymes indicated that SoPAL, SoUFGT3, and SoUFGT4 were possible candidate genes for anthocyanin biosynthesis in red-purple spinach. The expression patterns of transcription factors indicated that two SoMYB genes, three SobHLH genes, and one SoWD40 gene were drastically up-regulated and co-expression in red-purple spinach, suggesting an essential role of regulatory genes in the anthocyanin biosynthesis of spinach. These results will enhance our understanding of the molecular mechanisms of anthocyanin biosynthesis in purple spinach. PMID- 29787682 TI - Maternal Perception of Adequacy of Mother's Milk Among Mothers Giving Birth at a Teaching Hospital in Sri Lanka. AB - BACKGROUND: Sri Lanka boasts high rates of early and exclusive breastfeeding. Perceived inadequacy of milk, a global problem, is the main cause for early cessation of breastfeeding. Research Aims: The aims of this study are to (a) determine the prevalence, (b) identify the risk factors, and (c) ascertain the association that maternal psychological distress has with perceived inadequacy of milk (PIM), among mothers during the early postpartum period. Identifying and addressing modifiable risk factors for PIM may improve mothers' satisfaction with breastfeeding. METHODS: A cross-sectional descriptive study of mothers ( n = 249) during the first week after birth was conducted at Colombo North Teaching Hospital (Ragama, Sri Lanka) from May 1, 2016, to June 10, 2016. Participants were recruited when the infant was more than 24 hours but less than 7 days old. A self-administered questionnaire, including the six-item Kessler Psychological Distress Scale, was used. RESULTS: The majority of mothers (78%) perceived their milk quantity to be adequate. A family member telling mothers that their milk supply was low had the most significant associations with perceived inadequacy. Other associations were antenatal maternal complications and birth by cesarean section. Kessler scores indicating psychological distress occurred in 26% of all participating mothers, with a higher mean score in those with PIM. CONCLUSIONS: Sri Lankan family members should be educated further about normal patterns of milk production during the postpartum period. The authors recommend that PIM be included in screening tools for postpartum depression in Sri Lanka. PMID- 29787683 TI - MicroRNAs as potential regulators of platelet function and bleeding diatheses. AB - Although a growing number of studies suggest that microRNAs (miRNAs) play a relevant role in platelet biology, their implications in bleeding diatheses are starting to be investigated. Indeed, several studies have shown that alterations in the intracellular levels of highly expressed platelet miRNAs provoke a thrombotic phenotype. On the other hand, primary immune thrombocytopenia (ITP), which is considered the hallmark of acquired bleeding disorders, has been recently associated with altered levels of miRNAs in peripheral blood mononuclear cells, plasma, and platelets. In this review, we will focus on miRNAs that may affect the hemostatic and thrombotic functions of platelets, and we will discuss the different studies that have attempted to associate miRNAs with regulatory mechanisms of ITP. PMID- 29787684 TI - Trends and variation in prescribing of low-priority treatments identified by NHS England: a cross-sectional study and interactive data tool in English primary care. AB - Objectives NHS England recently announced a consultation seeking to discourage the use of treatments it considers to be low-value. We set out to produce an interactive data resource to show savings in each NHS general practice and to assess the current use of these treatments, their change in use over time, and the extent and reasons for variation in such prescribing. Design Cross-sectional analysis. Setting English primary care. Participants English general practices. Main outcome measures We determined the cost per 1000 patients for prescribing of each of 18 treatments identified by NHS England for each month from July 2012 to June 2017, and also aggregated over the most recent year to assess total cost and variation among practices. We used mixed effects linear regression to determine factors associated with cost of prescribing. Results Spend on low-value treatments was L153.5 m in the last year, across 5.8 m prescriptions (mean, L26 per prescription). Among individual treatments, liothyronine had the highest prescribing cost at L29.6 m, followed by trimipramine (L20.2 m). Over time, the overall total number of low-value prescriptions decreased, but the cost increased, although this varied greatly between treatments. Three treatment areas increased in cost and two increased in volume, all others reduced in cost and volume. Annual practice level spending varied widely (median, L2262 per thousand patients; interquartile range L1439 to L3298). Proportion of patients over 65 was strongly associated with low-value prescribing, as was Clinical Commissioning Group. Our interactive data tool was deployed to OpenPrescribing.net where monthly updated figures and graphs can be viewed. Conclusions Prescribing of low value treatments is extensive but varies widely by treatment, geographic area and individual practice. Despite a fall in prescription numbers, the overall cost of prescribing for low-value items has risen. Prescribing behaviour is clustered by Clinical Commissioning Group, which may represent variation in the optimisation efficiency of medicines, or in some cases access inequality. PMID- 29787685 TI - IBFAN News Brief: Who We Are, What We Do. PMID- 29787686 TI - Social Support for Breastfeeding in the Era of mHealth: A Content Analysis. AB - BACKGROUND: Several barriers to successful breastfeeding exist, including a lack of support from peers or professionals. With the emergence of mobile health (mHealth) tools to provide additional breastfeeding support, a more thorough review of social support resources was needed. Research Aim: The aim of this study was to determine mHealth breastfeeding support resources and characterize the type of social support they provide. METHODS: A content analysis of mHealth programs ( n = 65), including text messaging ( n = 12) and mobile applications ( n = 53), was conducted on the basis of searches of the iTunes and Google Play stores ( n = 50) and PubMed, the Cumulative Index of Nursing and Allied Health, and American Business Information/INFORM Complete Plus ( n = 15). Results were then dual-coded for key characteristics and types of support provided. RESULTS: Thirty-eight apps (76%) were free to users, 14 (28%) were offered in a variety of languages, and 47 (94%) provided informational support. The mobile applications were targeted largely to postpartum women, focused on breastfeeding duration, and included troubleshooting information. Mobile applications often included media components ( n = 12 [24%]); few were tailored or personalized ( n = 5 [10%]) and interactive ( n = 15 [30%]). Text-messaging programs were available in a variety of countries ( n = 7 [58%]) and provided mostly informational support ( n = 5 [42%]), were pro-breastfeeding ( n = 12 [100%]), were targeted to both pregnant and postpartum women ( n = 6 [50%]), focused on both breastfeeding initiation and duration ( n = 9 [75%]), and had two-way interactivity ( n = 6 [50%]) and personalization ( n = 5 [42%]). CONCLUSIONS: Although freely available mobile applications and text-messaging programs exist, with potential for wide reach, the majority provide only informational support. These programs would benefit from additional study of their usefulness. PMID- 29787687 TI - Rapid determination of polar pesticides and plant growth regulators in fruits and vegetables by liquid chromatography/tandem mass spectrometry. AB - A simple high-throughput liquid chromatography/tandem mass spectrometry (LC MS/MS) multiresidue analysis method was developed for the simultaneous determination of polar pesticides, plant growth regulators and other polar compounds. These included amitrole, chlormequat, mepiquat, cyromazine, ETU, PTU, perchlorate, and daminozide using a mixed-mode column. A 10 g test portion was shaken with acidified methanol for 10 min. After centrifugation, the sample extract was injected and analyzed within 11 min by LC-MS-MS. This column eliminated the need for derivatization or the use of ion paring reagent. Two MS MS transitions were monitored in the method for each target compound to achieve true positive identification. Eight isotopically-labeled internal standards corresponding to each analyte were used to correct for matrix suppression effect and/or instrument signal drift. The average recovery for all analytes at 20, 40, and 250 ng/g (n = 6) ranged from 73-136%, with a relative standard deviation of <= 20%. PMID- 29787688 TI - Intake and Factors Associated with Consumption of Pureed Food in Long Term Care: An Analysis of Making the Most of Mealtimes (M3) Project. AB - Residents living in long term care (LTC) who consume a pureed diet tend to have inadequate intake; understanding factors associated with poor intake in this group of residents is not well established. This study examined the adequacy of nutrient intake among LTC residents consuming a pureed diet and the factors associated with this intake (n = 67). Data was collected as part of a cross sectional study conducted in 32 LTC homes. Weighed food intake was measured on three non-consecutive days and analyzed using Food Processor software. Intake of nutrients were adjusted for intra-individual variability and compared to the Estimated Average Requirement or Adequate Intake for women only. Consumers of a pureed diet had low micronutrient intakes. Multivariate analysis found that the average number of staff assisting with a meal was associated with energy and protein intake. Overcoming eating challenges, careful menu planning and nutrient dense options for pureed diets in LTC are recommended. PMID- 29787689 TI - Patient-specific multiscale computational fluid dynamics assessment of embolization rates in the hybrid Norwood: effects of size and placement of the reverse Blalock-Taussig shunt. AB - The hybrid Norwood operation is performed to treat hypoplastic left heart syndrome. Distal arch obstruction may compromise flow to the brain. In a variant of this procedure, a synthetic graft (reverse Blalock-Taussig shunt) is placed between the pulmonary trunk and innominate artery to improve upper torso blood flow. Thrombi originating in the graft may embolize to the brain. In this study, we used computational fluid dynamics and particle tracking to investigate the patterns of particle embolization as a function of the anatomic position of the reverse Blalock-Taussig shunt. The degree of distal arch obstruction and position of particle origin influence embolization probabilities to the cerebral arteries. Cerebral embolization probabilities can be reduced by as much as 20% by optimizing graft position, for a given arch geometry, degree of distal arch obstruction, and particle origin. There is a tradeoff, however, between cerebral pulmonary and coronary embolization probabilities. PMID- 29787690 TI - Breastfeeding Practices Among Hispanic and Non-Hispanic Women at the Postpartum Visit. AB - BACKGROUND: Breastfeeding is an active area in public health advocacy. Despite documented benefits for infants and mothers, exclusive breastfeeding is not universal. Ethnicity, among other variables, has been shown to influence breastfeeding practice. Research aim: Our study aimed to determine which variables are associated with infant feeding patterns at the postpartum visit; compare the sociodemographic variables associated with infant feeding patterns between Hispanic and non-Hispanic mothers; and determine the odds of exclusive breastfeeding, mixed feeding, and exclusive formula feeding associated with sociodemographic characteristics. METHODS: A retrospective, cross-sectional two group comparison design was used. Hispanic and non-Hispanic women's ( N = 666) infant feeding patterns at 6-week postpartum were analyzed. Group comparisons were made of the demographic characteristics and infant feeding practice. RESULTS: Thirty-four percent of Hispanic participants reported exclusive breastfeeding compared with 59% of non-Hispanic White participants. Language and body mass index were significantly associated with infant feeding patterns among Hispanic participants. Compared with non-Hispanic White participants, Hispanic participants had increased odds of reporting mixed feeding and exclusive formula feeding. CONCLUSION: Breastfeeding initiatives should target English-speaking Hispanic mothers and obese Hispanic mothers to align breastfeeding rates with medical recommendations. Healthcare providers may benefit from additional training to address barriers to breastfeeding among obese women and to provide culturally sensitive support that encourages continued breastfeeding in this population. PMID- 29787691 TI - The Influence of Spinal Cord Injury on Breastfeeding Ability and Behavior. AB - BACKGROUND: Lactation dysfunction following spinal cord injury has been noted in the literature. However, researchers have often grouped together all women of physical disability or do not account for injury level. The extent of lactation dysfunction and influence of spinal cord injury on breastfeeding ability and behavior is not well understood. Research aim: This study aimed to identify major barriers to lactation and breastfeeding related to spinal cord injury, specifically comparing high- and low-level injuries. METHODS: A retrospective cross-sectional survey design was used. Two online questionnaires were developed and completed by women ( N = 52) who chose to breastfeed with spinal cord injury, primarily in Canada and Sweden. RESULTS: The first questionnaire was completed by 52 women with spinal cord injury; 38 of the original 52 participants completed the second questionnaire. Of the 52 women, 28 (53.8%) had high-level spinal cord injury (at or above T6) and 24 (46.1%) had low-level injury (below T6). On the second questionnaire, 14 (77.8%) women with high-level injury reported insufficient milk production or ejection. Only 35% of women ( n = 7) with low level injury reported the same. Autonomic dysreflexia was experienced by 38.9% of women ( n = 7) with high-level injury. Exclusive breastfeeding duration was significantly shorter ( p < .05) in the high-level injury group (3.3 months) compared with women with low-level injury (6.5 months). CONCLUSION: These results further support the notion that spinal cord injury (particularly at or above T6) disrupts lactation and is associated with shorter breastfeeding duration. Autonomic dysreflexia should be addressed in prospective mothers with high-level spinal cord injury. PMID- 29787692 TI - Comparing Different Methods of Measuring Accommodative Amplitude with Hofstetter's Normative Values in a Ghanaian Population. AB - AIM: Amplitude of accommodation (AoA) can be determined clinically using different methods. Some methods are known to be more reliable than others for measuring AoA in different age categories. The purpose of this study was to compare Hofstetter's age-expected norms with five recommended methods of measuring AoA in order to determine age-appropriate techniques for a Ghanaian population. MATERIALS AND METHODS: AoA was measured using four subjective methods (push-up, push-down, minus lens, and modified push-up) and one objective method, the modified dynamic retinoscopy. The amplitudes obtained by each technique were compared to each other and also compared to the age-expected amplitudes as predicted by Hofstetter's equations. RESULTS: 352 non-presbyopes aged 10-39 years were included in this study. All five methods except the push-up (p = 0.089) and modified push-up (p = 0.081) differed significantly from Hofstetter's data, while the modified dynamic retinoscopy recorded the strongest agreement with Hofstetter's average (ICC = 0.78, p ? 0.001). With reference to Hofstetter's expected AoA, the minus lens, push-down, modified dynamic retinoscopy, and modified push-up methods underestimated AoA by -4.18D, -1.99D, -0.48D, and 0.43D, respectively. As age increased, underestimated AoA values by the minus lens (10-19 years: -5.57D, 20-29 years: -3.50D, 30-39 years: -2.39D), modified push-up (10-19 years: -1.51D, 20-29 years: +0.40D, 30-39 years: +0.56D), and push down (10-19 years: -2.90D, 20-29 years: -1.07D, 30-39 years: -1.46D) methods decreased but the modified push-up in relation to Hofstetter's expected was most accurate for the older age. The push-up, on the other hand, overestimated accommodation in all age categories by +0.42D (10-19 years: +0.01D, 20-29 years: +0.82D, 30-39 years: 0.67D). Thus, the push-up method became more accurate as age decreased. CONCLUSION: This study suggested that Hofstetter's formulae could be used to predict the amplitudes of Ghanaian non-presbyopes aged 10-39 years using the push-up and modified push-up. With regard to Hofstetter's data, the push-up method was more accurate for the younger age-group 10-19 years while the modified push-up was more accurate for the older age-group 20-39. PMID- 29787693 TI - Quadriceps Rate of Torque Development and Disability in Persons With Tibiofemoral Osteoarthritis. AB - Background Declines in the ability to rapidly generate quadriceps muscle torque may underlie disability in individuals with tibiofemoral osteoarthritis. Objective To determine whether quadriceps rate of torque development (RTD) predicts self-reported disability and physical performance outcomes in individuals with tibiofemoral osteoarthritis. Methods This controlled laboratory, cross-sectional study assessed quadriceps strength and RTD in 76 individuals (55% female; mean +/- SD age, 61.83 +/- 7.11 years) with symptomatic and radiographic tibiofemoral osteoarthritis. Early (0-50 milliseconds), late (100-200 milliseconds), and overall peak RTDs were quantified in the symptomatic (involved) and contralateral limbs and used to calculate bilateral average values. Disability was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale and 3 physical performance tests, including the (1) 20-m fast-paced walk, (2) 30-second chair stand, and (3) timed stair climb. Separate univariate regression models were used to determine the unique associations among measures of quadriceps RTD, WOMAC function score, and physical performance outcomes after accounting for quadriceps strength (change in R2). Results Greater involved-side late RTD and greater bilateral average early RTD were associated with faster walking (change in R2 = 0.05, P = .013 and change in R2 = 0.05, P = .043, respectively). Greater bilateral average late RTD was associated with faster walking (change in R2 = 0.20, P<.001) and faster stair climb (change in R2 = 0.11, P = .001). No quadriceps RTD variable was significantly associated with WOMAC function score (change in R2 range, <0.01-0.017). Conclusion Involved-limb quadriceps RTD was weakly associated with physical performance outcomes, but not self-reported disability, in individuals with tibiofemoral osteoarthritis. Bilateral average quadriceps RTD was moderately associated with walking speed. Level of Evidence Prognosis, level 2b. J Orthop Sports Phys Ther 2018;48(9):694-703. Epub 22 May 2018. doi:10.2519/jospt.2018.7898. PMID- 29787694 TI - Gait Alterations in Femoroacetabular Impingement Syndrome Differ by Sex. AB - Background Femoroacetabular impingement (FAI) syndrome may affect gait kinematics differently between males and females. Objectives To investigate whether individuals with FAI syndrome have different hip and pelvic motion during gait, at their preferred speed and a prescribed speed, compared to individuals of the same sex without pain. Methods Twenty-one participants (11 males and 10 females) with FAI syndrome and 41 participants (19 males and 22 females) without hip pain were included in this case-control laboratory study. There were no differences between the 2 groups in age, body mass index, and activity score. Kinematic data for all participants were collected while walking at a preferred speed and at 1.25 m/s. For sex and walking speed, linear regression analyses were used to examine the effect of group and the interaction of group by limb. Results At both speeds, males with FAI syndrome walked with more than 6 degrees less peak hip extension (P<=.018), 5 degrees greater anterior pelvic tilt (P<=.020), and 5 degrees less posterior pelvic tilt (P<=.018) compared to males without hip pain. Females with FAI syndrome walked with 2 degrees less hip extension (P<=.012) and at least 3 degrees more hip adduction (P<.001) in the more painful hip than in the less painful hip at both speeds. Conclusion Males and females with FAI syndrome have different gait alterations when compared to a same-sex comparison group. In males, differences were between groups. In females with FAI syndrome, differences were between the more painful and the less painful limb. J Orthop Sports Phys Ther 2018;48(8):649-658. Epub 22 May 2018. doi:10.2519/jospt.2018.7913. PMID- 29787695 TI - Incidence of Musculoskeletal Injury in US Army Unit Types: A Prospective Cohort Study. AB - BACKGROUND: Musculoskeletal injuries during military service are a primary source of disability, resulting in 2.4 million annual health care visits and 25 million limited-duty days. While the injury incidence during basic training is well documented, there is little understanding of injury distribution by organization type in the US Army following initial training. OBJECTIVE: To compare injury incidence, distribution, and impact across various military units. METHODS: In this prospective observational cohort study, comprehensive injury data from subject questionnaires and medical chart reviews were collected over 12 months for 1430 initially healthy Army personnel, representing combat, combat support, combat service support, and ranger units. Health care utilization and time loss due to injury were also collected. RESULTS: Of 1430 soldiers, 481 (33.6%) had time-loss injury, 222 (15.5%) were injured without limited work, 60 (4.2%) reported an injury but did not seek medical care, and 667 (46.6%) were uninjured. Across the whole sample, injuries were responsible for 5.9 +/-14.4 medical visits per soldier, 21 902 days of limited work, and $1 337 000 ($1901 +/- $6535 per soldier) in medical costs. Considering only those reporting injury, each person averaged 36.3 +/- 59.7 limited-work days. The injury incidence was highest in combat service support units (65.6%), with a risk ratio 1.60 times that of the reference group (combat, 41.1%). CONCLUSION: Combat support and combat service support personnel were more likely to have 1 or more injuries compared to rangers and combat personnel. The higher relative risk of injury in support units should be explored further. J Orthop Sports Phys Ther 2018;48(10):749-757. Epub 22 May 2018. doi:10.2519/jospt.2018.7979. PMID- 29787696 TI - Impact of Risk Adjustment on Provider Ranking for Patients With Low Back Pain Receiving Physical Therapy. AB - Background The impact of risk adjustment on clinic quality ranking for patients treated in physical therapy outpatient clinics is unknown. Objectives To compare clinic ranking, based on unadjusted versus risk-adjusted outcomes for patients with low back pain (LBP) who are treated in physical therapy outpatient clinics. Methods This retrospective cohort study involved a secondary analysis of data from adult patients with LBP treated in outpatient physical therapy clinics from 2014 to 2016. Patients with complete outcomes data at admission and discharge were included to develop the risk-adjustment model. Clinics with complete outcomes data for at least 50% of patients and at least 10 complete episodes of care per clinician per year were included for ranking assessment. The R2 shrinkage and predictive ratio were used to assess overfitting. Agreement between unadjusted and adjusted rankings was assessed with percentile ranking by deciles or 3 distinct quality ranks based on uncertainty assessment. Results The primary sample included 414 125 patients (mean +/- SD age, 57 +/- 17 years; 60% women) treated by 12 569 clinicians from 3048 clinics from all US states; 82% of patients from 2107 clinics were included in the ranking assessment. The R2 shrinkage was less than 1%, with a predictive ratio of 1. Risk adjustment impacted ranking for 70% or 31% of clinics, based on deciles or 3 distinct quality levels, respectively. Conclusion Important changes in ranking were found after adjusting for basic patient characteristics of those admitted to physical therapy for treatment of LBP. Risk-adjustment profiling is necessary to more accurately reflect quality of care when treating patients with LBP. Level of Evidence Therapy, level 2b. J Orthop Sports Phys Ther 2018;48(8):637-648. Epub 22 May 2018. doi:10.2519/jospt.2018.7981. PMID- 29787697 TI - Rehabilitation Practice Patterns Following Anterior Cruciate Ligament Reconstruction: A Survey of Physical Therapists. AB - BACKGROUND: Recovery from anterior cruciate ligament reconstruction (ACLR) requires an intensive course of postoperative rehabilitation. Although guidelines outlining evidence-based rehabilitation recommendations have been published, actual practice patterns of physical therapists are unknown. OBJECTIVES: To analyze the current landscape of clinical practice as it pertains to rehabilitation progression and the use of time and objective criteria in rehabilitation following ACLR. METHODS: In this cross-sectional study, an online survey was distributed to members of the Academy of Orthopaedic Physical Therapy, the American Academy of Sports Physical Therapy, and the Private Practice Section of the American Physical Therapy Association between January and March 2017. RESULTS: The study analyzed a sample of 1074 responses. Supervised physical therapy was reported to last 5 months or less by 56% of survey respondents. The most frequent time frames for activity progression were 3 to 4 months (58%) for jogging, 4 to 5 months (50%) for modified sports activity, and 9 to 12 months (40%) for unrestricted sports participation. More than 80% of respondents reported using strength and functional measures during rehabilitation. Of those physical therapists who assessed strength, 56% used manual muscle testing as their only means of strength testing. Single-limb hop testing (89%) was the most frequently reported measure used to allow patients to begin modified sports activity following ACLR. Performance criteria for strength and functional tests varied significantly across all phases of rehabilitation. The 45% of respondents who reported using patient-reported outcome measures indicated that just under 10% of those measures involved fear or athletic confidence scales. CONCLUSION: Considerable variation in practice exists among American Physical Therapy Association members regarding rehabilitation following ACLR. This variability in practice may contribute to suboptimal outcomes and confusion among practitioners and patients. J Orthop Sports Phys Ther 2018;48(10):801-811. Epub 22 May 2018. doi:10.2519/jospt.2018.8264. PMID- 29787698 TI - US Ethnic Group Differences in Family Member Support for People With Diabetes in the 2nd Diabetes Attitudes, Wishes and Needs (DAWN2) Study. AB - Purpose The purpose of the study was to describe the perceptions of family members (FM) and people with diabetes (PWD) regarding the frequency and helpfulness of FM support for PWD, including differences among US ethnic groups. Methods The US 2nd Diabetes Attitudes, Wishes and Needs (DAWN2) substudy was a survey of independent samples of 238 adult FM and 540 adult PWD. Outcome measures included ratings by FM and PWD of the frequency and perceived helpfulness of 7 FM support behaviors and composite scores for frequency and helpfulness. Results Ratings of individual FM support behaviors were strongly correlated between FM and PWD but significantly different among behaviors. FM and PWD reported most frequent support for listening, assisting, and doing activities with PWD and reporting PWD was doing poorly least frequently. Both groups reported listening, assisting, and reporting PWD was doing well as most helpful; reporting PWD was doing poorly was least helpful. PWD rated support and helpfulness of most behaviors lower than FM. Composite measures of support frequency and helpfulness were strongly correlated for both FM and PWD. Ethnic minority PWD and FM reported most support behaviors as more frequent and more helpful than non-Hispanic white Americans. Conclusions FM more frequently engage in the support behaviors they view as most helpful, but PWD perceive support to be less frequent and less helpful than FM. FM support differs across ethnic groups, with ethnic minorities reporting higher support frequency and helpfulness. Diabetes care providers should consider ethnic group differences in FM support for PWD. PMID- 29787700 TI - Predictors of excess birth weight in Brazil: a systematic review. AB - OBJECTIVE: To describe the main predictors for excess birth weight in Brazilian children. DATA SOURCES: Systematic review carried out in the bibliographic databases: PubMed/MEDLINE, Cochrane, Scopus, Web of Science, and LILACS. The research in the gray literature was performed using the Google Scholar database. The bias risk analysis was adapted from the Downs and Black scale, used to evaluate the methodology of the included studies. DATA SYNTHESIS: Using the classifications of fetal macrosomia (>4000g or >=4000g) and large for gestational age (above the 90th percentile), 64 risk factors for excess birth weight were found in 33 scientific articles in the five regions of the country. Of the 64 risk factors, 31 were significantly associated with excess birth weight, with excess gestational weight gain, pre-gestational body mass index >=25kg/m2, and gestational diabetes mellitus being the most prevalent. CONCLUSION: The main predictors for excess birth weight in Brazil are modifiable risk factors. The implementation of adequate nutritional status in the gestational period and even after childbirth appears to be due to the quality and frequency of the follow-up of the mothers and their children by public health agencies. PMID- 29787701 TI - The effect of sleep quality on academic performance is mediated by Internet use time: DADOS study. AB - OBJECTIVE: The aims of the present study were to analyze the association of sleep patterns with academic and cognitive performance in adolescents, and to test the potential mediating effect of different activities of screen media usage on this association. METHODS: A sample of 269 adolescents (140 boys) aged 14 years from the baseline data of the Deporte, ADOlescencia y Salud study completed questionnaires about sleep quality, cognitive performance, and leisure-time sedentary behaviors. Sleep duration was objectively computed using a wrist-worn GENEActiv accelerometer and academic performance was analyzed through school records. RESULTS: Sleep quality (but not sleep duration) was associated with all the academic performance indicators (all p<0.05). Analysis of covariance revealed higher grades among adolescents with better sleep quality (PSQI<=5; all p<0.05). These analyses showed no differences regarding cognitive performance. Internet use time was revealed as a mediator of the association between sleep quality and academic performance, being significant for all academic performance indicators (PM ranging from 15.5% to 16.0%). CONCLUSIONS: The association between sleep quality and academic performance in adolescents is mediated by time of Internet use. Overall, reducing Internet use in adolescents could be an achievable intervention for improving sleep quality, with potentially positive effects on academic performance. PMID- 29787702 TI - Lip Morphology in Patients With Facial Asymmetry Can Be Corrected by 2-Jaw Surgery. AB - PURPOSE: Surgical orthodontic patients with facial asymmetry frequently show asymmetry of the lips, and this is often a major complaint of patients. This study investigated whether lip asymmetry associated with the maxilla and mandible was improved when 2-jaw surgery was performed in surgical orthodontic treatment. MATERIALS AND METHODS: Inclusion criteria for this retrospective cohort study were 1) an anteroposterior maxillary relation defined as skeletal Class I; 2) menton (Me) tranverse deviation greater than 5.0 mm; 3) maxillary cant greater than 3.0 degrees ; and 4) 2-jaw surgery. Primary predictor variables in this study were skeletal morphologic measurements (Me deviation, maxillary cant, and maxillary distance ratio) before and after treatment. Outcome variables were lip morphology measurements (labial commissure distance, lip angle, and lip area). Additional variables included age and gender. Vertical distances, angles, and area of the upper and lower lips were measured and compared before and after treatment. Hard tissues were measured using posteroanterior cephalograms. Paired t test and correlation coefficients were calculated. RESULTS: Fourteen patients (4 men [28.5%] and 10 women [71.5%]; mean age, 29 yr) were included. Meaningful changes were observed in distance and angle measurements of the lips from before to after treatment. In area measurement, ratios of the area on the deviated side to that on the contralateral side for the upper and lower lips changed markedly and were close to 1.0 compared with before treatment. A relevant correlation was found between change in Me deviation and change in ratio of the height of the labial commissure. CONCLUSION: In cases of facial asymmetry caused by deviation of the maxilla and mandible, lip asymmetry can be adequately corrected by leveling the canted occlusal plane and positioning the Me toward the midline with 2-jaw surgery. PMID- 29787704 TI - CCTalpha Commands Phospholipid Homeostasis from the Nucleus. AB - Enzyme control by their products facilitates cellular homeostasis, but for phospholipids, feedback mechanisms also arise from changes in membrane physical properties. In this issue of Developmental Cell, Haider et al. (2018) show that in many actively growing cells, an enzyme of phosphatidylcholine synthesis senses lipid packing in the nuclear membrane. PMID- 29787703 TI - Misshapen Connects Food, Mechanosensing, and Intestinal Growth. AB - Adult tissues such as intestinal epithelium can rapidly adapt their growth in response to environmental stimuli. In this issue of Developmental Cell, Li et al. (2018) demonstrate that gut epithelium stretching caused by food ingestion drives Drosophila intestinal growth via Hippo pathway regulation. PMID- 29787705 TI - The Incredible Shrinking Spindle. AB - As cell size decreases during the reductive divisions of early development, intracellular structures must shrink to fit. In this issue of Developmental Cell, Lacroix et al. (2018) identify a conserved mechanism of spindle scaling in nematode and sea urchin embryos whereby spindle microtubule polymerization rates decrease as development proceeds. PMID- 29787706 TI - Circuit Wiring: Neurite Speed Dating versus Stable Synaptic Matchmaking. AB - Understanding the mechanisms establishing the complex but precise pattern of connectivity characterizing neural circuits remains an immense challenge. In a recent issue of Neuron, Mao and colleagues (2018) provide new insights by showing that the activation kinetics of EphB2, a transmembrane receptor tyrosine kinase, control whether dendritic filopodia makes a synapse with candidate axons. PMID- 29787707 TI - Pulmonary Neuroendocrine Cells: Sensors and Sentinels of the Lung. AB - Organisms have developed cellular "antennas" to sense, interpret, and integrate environmental stimuli. In a recent issue of Science, Sui et al. (2018) demonstrate that discrete clusters of pulmonary neuroendocrine cells in the lung can sense airborne allergens and relay signals to stimulate immune cells and induce tissue/organ-wide responses. PMID- 29787708 TI - Emerging Links between Lipid Droplets and Motor Neuron Diseases. AB - Lipid droplets (LDs) are ubiquitous fat storage organelles and play key roles in lipid metabolism and energy homeostasis; in addition, they contribute to protein storage, folding, and degradation. However, a role for LDs in the nervous system remains largely unexplored. We discuss evidence supporting an intimate functional connection between LDs and motor neuron disease (MND) pathophysiology, examining how LD functions in systemic energy homeostasis, in neuron-glia metabolic coupling, and in protein folding and clearance may affect or contribute to disease pathology. An integrated understanding of LD biology and neurodegeneration may open the way for new therapeutic interventions. PMID- 29787710 TI - Microtubule Dynamics Scale with Cell Size to Set Spindle Length and Assembly Timing. AB - Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during embryo cleavage in the nematode Caenorhabditis elegans and sea urchin Paracentrotus lividus. We reveal a common scaling mechanism, where the growth rate of spindle microtubules scales with cell volume, which explains spindle shortening. Spindle assembly timing is, however, constant throughout successive divisions. Analyses in silico suggest that controlling the microtubule growth rate is sufficient to scale spindle length and maintain a constant assembly timing. We tested our in silico predictions to demonstrate that modulating cell volume or microtubule growth rate in vivo induces a proportional spindle size change. Our results suggest that scalability of the microtubule growth rate when cell size varies adapts spindle length to cell volume. PMID- 29787712 TI - Myonuclear Positioning and Aneurysms Are LINC'd by Ariadne. PMID- 29787711 TI - Tild-CRISPR Allows for Efficient and Precise Gene Knockin in Mouse and Human Cells. AB - The targeting efficiency of knockin sequences via homologous recombination (HR) is generally low. Here we describe a method we call Tild-CRISPR (targeted integration with linearized dsDNA-CRISPR), a targeting strategy in which a PCR amplified or precisely enzyme-cut transgene donor with 800-bp homology arms is injected with Cas9 mRNA and single guide RNA into mouse zygotes. Compared with existing targeting strategies, this method achieved much higher knockin efficiency in mouse embryos, as well as brain tissue. Importantly, the Tild CRISPR method also yielded up to 12-fold higher knockin efficiency than HR-based methods in human embryos, making it suitable for studying gene functions in vivo and developing potential gene therapies. PMID- 29787709 TI - Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions. AB - Caspases are best characterized for their function in apoptosis. However, they also have non-apoptotic functions such as apoptosis-induced proliferation (AiP), where caspases release mitogens for compensatory proliferation independently of their apoptotic role. Here, we report that the unconventional myosin, Myo1D, which is known for its involvement in left/right development, is an important mediator of AiP in Drosophila. Mechanistically, Myo1D translocates the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells where Dronc promotes the activation of the NADPH-oxidase Duox for reactive oxygen species generation and AiP in a non-apoptotic manner. We propose that the basal side of the plasma membrane constitutes a non-apoptotic compartment for caspases. Finally, Myo1D promotes tumor growth and invasiveness of the neoplastic scrib RasV12 model. Together, we identified a new function of Myo1D for AiP and tumorigenesis, and reveal a mechanism by which cells sequester apoptotic caspases in a non-apoptotic compartment at the plasma membrane. PMID- 29787714 TI - Genomic Analyses of Pre-European Conquest Human Remains from the Canary Islands Reveal Close Affinity to Modern North Africans. PMID- 29787715 TI - Muscle stem cells. AB - Feige and Rudnicki introduce muscle stem cells. PMID- 29787713 TI - Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+874 A>T polymorphism. AB - INTRODUCTION: Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-gamma production can be influenced by genetic polymorphisms, of which the IFNG+874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG+874 A/T polymorphism on interferon-gamma test performance. METHODS: Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG+874 genotype and the IFN-gamma levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB(r) Gold In-Tube). RESULTS: IFN-gamma production was not influenced by the IFNG+874 genotype, regardless of antigen or mitogen based stimulation, which suggests that other genes may influence IFN-gamma production in response to mycobacteria. The IFNG+874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. CONCLUSIONS: The IFNG+874 polymorphism was not shown to influence QuantiFERON-TB(r) Gold In-Tube test performance in an admixed population from northeastern Brazil. PMID- 29787717 TI - Imminent extinction in the wild of the world's largest amphibian. AB - Species with large geographic ranges are considered resilient to global decline [1]. However, human pressures on biodiversity affect increasingly large areas, in particular across Asia, where market forces drive overexploitation of species [2]. Range-wide threat assessments are often costly and thus extrapolated from non-representative local studies [3]. The Chinese giant salamander (Andrias davidianus), the world's largest amphibian, is thought to occur across much of China, but populations are harvested for farming as luxury food [4]. Between 2013 and 2016, we conducted field surveys and 2,872 interviews in possibly the largest wildlife survey conducted in China. This extensive effort revealed that populations of this once-widespread species are now critically depleted or extirpated across all surveyed areas of their range, and illegal poaching is widespread. PMID- 29787718 TI - Methodological problems in a study of fetal visual perception. AB - Reid et al.[1] analysed data from 39 third-trimester fetuses, concluding that they showed a preferential head-orienting reaction towards lights projected through the uterine wall in a face-like arrangement, as opposed to an inverted triangle of dots. These results imply not only that assessment of visual perceptive responses is possible in prenatal subjects, but also that a measurable preference for faces exists before birth. However, we have identified three substantial problems with Reid et al.'s [1] method and analyses, which we outline here. PMID- 29787716 TI - The Chinese giant salamander exemplifies the hidden extinction of cryptic species. AB - Overexploitation, habitat destruction, human-driven climate change and disease spread are resulting in the extinction of innumerable species, with amphibians being hit harder than most other groups [1]. Few species of amphibians are widespread, and those that are often represent complexes of multiple cryptic species. This is especially true for range-restricted salamanders [2]. Here, we used the widespread and critically endangered Chinese giant salamander (Andrias davidianus) to show how genetically uninformed management efforts can negatively affect species conservation. We find that this salamander consists of at least five species-level lineages. However, the extensive recent translocation of individuals between farms, where the vast majority of extant salamanders now live, has resulted in genetic homogenization. Mitochondrial DNA (mtDNA) haplotypes from northern China now predominate in farms. Unfortunately, hybrid offspring are being released back into the wild under well-intentioned, but misguided, conservation management. Our findings emphasize the necessity of genetic assessments for seemingly well-known, widespread species in conservation initiatives. Species serve as the primary unit for protection and management in conservation actions [3], so determining the taxonomic status of threatened species is a major concern, especially for amphibians. The level of threat to amphibians may be underestimated, and existing conservation strategies may be inadvertently harmful if conducted without genetic assessment. PMID- 29787719 TI - Response to Scheel et al. AB - Scheel et al.[1] highlight three types of methodological concern with the work reported in our recent paper [2], related to analytical decisions, fetal behavior, and how light interfaces with maternal tissue. Here we outline why the issues raised do not detract from our originally reported conclusions. In our view, the procedural and analytical decisions that we made in our study [2] were the most appropriate given the uncharted territory that we explored. The best test of methodological robustness of our approach would be replication by another laboratory. PMID- 29787720 TI - The importance of true collaboration in efforts to increase diversity in genetic analyses. AB - In Michael Gross's recent article ('Mind the genome diversity gap'), he rightly states that global health equity demands an overhaul of the current approach to genetic analysis of psychiatric conditions, which relies heavily on European sample collections. Unfortunately, the article missed the mark in its description of work undertaken by the Broad Institute of MIT and Harvard, the Harvard T.H. Chan School of Public Health, and collaborative partners in Africa and Asia that aims to change the status quo. PMID- 29787721 TI - Memory: Ironing Out a Wrinkle in Time. AB - Individual hippocampal neurons encode time over seconds, whereas large-scale changes in population activity of hippocampal neurons encode time over minutes and days. New research shows how the hippocampus represents these multiple timescales simultaneously. PMID- 29787722 TI - Programmed DNA Elimination: Keeping Germline Genes in Their Place. AB - Each of our cells contains a full set of instructions needed to make an entire human: the genome. But a few special species buck this trend. A new study now identifies the first germline-specific gene in zebra finch, one of a small number of vertebrates that are known to undergo developmentally programmed DNA elimination. PMID- 29787723 TI - Evolution: More Mysticete Mysteries. AB - Fossils of one of the oldest relatives to baleen-bearing whales have been described from Antarctica. Aspects of its anatomy cast doubt on conventional views for the evolution of filter-feeding and body size in whales. PMID- 29787724 TI - Disease Tolerance: Linking Sickness Behaviours to Metabolism Helps Mitigate Malaria. AB - Malaria-infected mice exhibit a range of sickness behaviours, and experience metabolic shifts and physiological pathologies that result in reduced energy expenditure. Treating sick mice with glucose increases disease tolerance by improving the physiological and behavioural symptoms of malaria infection without affecting parasite loads. PMID- 29787725 TI - Sensory Coding: Neurons That Wire Together Fire Longer. AB - Sensory neurons for smell and taste in insects reside in sensilla. Experiments in bumblebees reveal an unusual benefit of this arrangement: interaction between co housed gustatory neurons promotes bursting in their responses and delays their adaptation. PMID- 29787726 TI - Hearing: Representing the Aural Wallpaper. AB - Human listeners appear to represent the textures of sounds through a process of automatic time averaging that exists beyond volition. This process distils likely background sounds into their summary statistics, a computationally efficient way of dealing with complex auditory scenes. PMID- 29787727 TI - Chromosome Biology: The Smc-Kleisin Enzymology Finally Comes of Age. AB - Cohesin and condensin are Smc-kleisin complexes responsible for shaping our chromosomes. Despite extensive genetic and genomic information available on their function, their biochemistry has been hard to study. Two recent studies finally bring exciting new insights into their enzymology. PMID- 29787728 TI - Sex: The End Is All You Need. AB - Sex is rewarding. Out of the many steps needed for successful mating, from courtship through copulation, the ultimate ejaculatory step in male fruit flies has profound rewarding properties. PMID- 29787729 TI - Respiration: Life Without Complex I. AB - Eukaryotic life has developed a fascinating and highly optimized system for energy transduction: the mitochondrial respiratory chain. Typically composed of five core protein complexes, we now learn from two studies that plant hemi parasites of the type Viscum cope without Complex I, the entry point of the classical respiratory system. PMID- 29787731 TI - An assay of optimal cytochrome c oxidase activity in fish gills. AB - Cytochrome c oxidase (COX) catalyzes the terminal oxidation reaction in the electron transport chain (ETC) of aerobic respiratory systems. COX activity is an important indicator for the evaluation of energy production by aerobic respiration in various tissues. On the basis of the respiratory characteristics of muscle, we established an optimal method for the measurement of maximal COX activity. To validate the measurement of cytochrome c absorbance, different ionic buffer concentrations and tissue homogenate protein concentrations were used to investigate COX activity. The results showed that optimal COX activity is achieved when using 50-100 MUg fish gill homogenate in conjunction with 75-100 mM potassium phosphate buffer. Furthermore, we compared branchial COX activities among three species of euryhaline teleost (Chanos chanos, Oreochromis mossambicus, and Oryzias dancena) to investigate differences in aerobic respiration of osmoregulatory organs. COX activities in the gills of these three euryhaline species were compared with COX subunit 4 (COX4) protein levels. COX4 protein abundance and COX activity patterns in the three species occurring in environments with various salinities increased when fish encountered salinity challenges. This COX activity assay therefore provides an effective and accurate means of assessing aerobic metabolism in fish. PMID- 29787732 TI - Randomized, Controlled, Phase 2 Trial of Povidone-Iodine/Dexamethasone Ophthalmic Suspension for Treatment of Adenoviral Conjunctivitis. AB - PURPOSE: To evaluate the efficacy/safety of an ophthalmic suspension of povidone iodine (PVP-I) 0.6% and dexamethasone 0.1% in patients with acute adenoviral conjunctivitis. DESIGN: Multicenter, randomized, vehicle-controlled, double masked trial. METHODS: Adults with a positive Rapid Pathogen Screening Adeno Detector Plus test were randomized 1:1:1 to PVP-I 0.6%/dexamethasone 0.1%, PVP-I 0.6%, or vehicle, bilaterally 4 times daily for 5 days (days 1-5). Patients were evaluated on days 3, 6, and 12 (+1-day window). Efficacy measures included clinical resolution and adenoviral eradication. RESULTS: Overall, 144 patients were included in the efficacy analysis (PVP-I/dexamethasone, n = 48; PVP-I, n = 50; vehicle, n = 46). The proportion of patients with clinical resolution (primary study eye with last observation carried forward [LOCF]) at the day 6 visit was higher with PVP-I/dexamethasone (31.3%) than with vehicle (10.9%; P = .0158) and PVP-I (18.0%; P = nonsignificant). The proportion with adenoviral eradication (primary study eye with LOCF) was higher with PVP-I/dexamethasone than with vehicle at the day 3 (35.4% vs 8.7%; P = .0019) and day 6 (79.2% vs 56.5%; P = .0186) visits and vs PVP-I (day 3 visit, 32.0%; day 6 visit, 62.0%; each P = nonsignificant). Treatment-emergent adverse events (AEs) occurred in 69.0% (vehicle), 62.7% (PVP-I), and 53.4% (PVP-I/dexamethasone) of patients in the safety dataset. Discontinuation owing to AEs occurred in 37 patients (vehicle, n = 16; PVP-I, n = 12; PVP-I/dexamethasone, n = 9). CONCLUSION: PVP I/dexamethasone appeared safe and well tolerated, and significantly improved clinical resolution and adenoviral eradication in patients with acute adenoviral conjunctivitis. PMID- 29787730 TI - Plant-Pathogen Warfare under Changing Climate Conditions. AB - Global environmental changes caused by natural and human activities have accelerated in the past 200 years. The increase in greenhouse gases is predicted to continue to raise global temperature and change water availability in the 21st century. In this Review, we explore the profound effect the environment has on plant diseases - a susceptible host will not be infected by a virulent pathogen if the environmental conditions are not conducive for disease. The change in CO2 concentrations, temperature, and water availability can have positive, neutral, or negative effects on disease development, as each disease may respond differently to these variations. However, the concept of disease optima could potentially apply to all pathosystems. Plant resistance pathways, including pattern-triggered immunity to effector-triggered immunity, RNA interference, and defense hormone networks, are all affected by environmental factors. On the pathogen side, virulence mechanisms, such as the production of toxins and virulence proteins, as well as pathogen reproduction and survival are influenced by temperature and humidity. For practical reasons, most laboratory investigations into plant-pathogen interactions at the molecular level focus on well-established pathosystems and use a few static environmental conditions that capture only a fraction of the dynamic plant-pathogen-environment interactions that occur in nature. There is great need for future research to increasingly use dynamic environmental conditions in order to fully understand the multidimensional nature of plant-pathogen interactions and produce disease resistant crop plants that are resilient to climate change. PMID- 29787733 TI - The major outer membrane protein of Legionella pneumophila Lpg1974 shows pore forming characteristics similar to the human mitochondrial outer membrane pore, hVDAC1. AB - Legionella pneumophila is an aerobic and nonspore-forming pathogenic Gram negative bacterium of the genus Legionella. It is the causative agent of Legionnaires' disease, also known as Legionellosis. The hosts of this organism are diverse, ranging from simple water borne protozoans such as amoebae to more complex hosts such as macrophages in humans. Genome analyses have shown the presence of genes coding for eukaryotic like proteins in several Legionella species. The presence of these proteins may assist L. pneumophila in its adaptation to the eukaryotic host. We studied the characteristics of a protein (Lpg1974) of L. pneumophila that shows remarkable homologies in length of the primary sequence and for the identity/homology of many amino acids to the voltage dependent anion channel (human VDAC1, Porin 31HL) of human mitochondria. Two different forms of Lpg1974 were overexpressed in Escherichia coli and purified to homogeneity: the one containing a putative N-terminal signal sequence and one without it. Reconstituted protein containing the signal sequence formed ion permeable pores in lipid bilayer membranes with a conductance of approximately 5.4 nS in 1 M KCl. When the predicted N-terminal signal peptide of Lpg1974 comprising an alpha-helical structure similar to that at the N-terminus of hVDAC1 was removed, the channels formed in reconstitution experiments had a conductance of 7.6 nS in 1 M KCl. Both Lpg1974 proteins formed pores that were voltage dependent and anion-selective similar to the pores formed by hVDAC1. These results suggest that Lpg1974 of L. pneumophila is indeed a structural and functional homologue to hVDAC1. PMID- 29787734 TI - Osteopathic Manipulative Treatment Including Specific Diaphragm Techniques Improves Pain and Disability in Chronic Nonspecific Low Back Pain: A Randomized Trial. AB - OBJECTIVE: To investigate the effects of an osteopathic manipulative treatment (OMT), which includes a diaphragm intervention compared to the same OMT with a sham diaphragm intervention in chronic nonspecific low back pain (NS-CLBP). DESIGN: Parallel group randomized controlled trial. SETTING: Private and institutional health centers. PARTICIPANTS: Participants (N=66) (18-60y) with a diagnosis of NS-CLBP lasting at least 3 months. INTERVENTIONS: Participants were randomized to receive either an OMT protocol including specific diaphragm techniques (n=33) or the same OMT protocol with a sham diaphragm intervention (n=33), conducted in 5 sessions provided during 4 weeks. MAIN OUTCOME MEASURES: The primary outcomes were pain (evaluated with the Short-Form McGill Pain Questionnaire [SF-MPQ] and the visual analog scale [VAS]) and disability (assessed with the Roland-Morris Questionnaire [RMQ] and the Oswestry Disability Index [ODI]). Secondary outcomes were fear-avoidance beliefs, level of anxiety and depression, and pain catastrophization. All outcome measures were evaluated at baseline, at week 4, and at week 12. RESULTS: A statistically significant reduction was observed in the experimental group compared to the sham group in all variables assessed at week 4 and at week 12 (SF-MPQ [mean difference -6.2; 95% confidence interval, -8.6 to -3.8]; VAS [mean difference -2.7; 95% confidence interval, -3.6 to -1.8]; RMQ [mean difference -3.8; 95% confidence interval, -5.4 to -2.2]; ODI [mean difference -10.6; 95% confidence interval, -14.9 to 6.3]). Moreover, improvements in pain and disability were clinically relevant. CONCLUSIONS: An OMT protocol that includes diaphragm techniques produces significant and clinically relevant improvements in pain and disability in patients with NS-CLBP compared to the same OMT protocol using sham diaphragm techniques. PMID- 29787735 TI - PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin. AB - Cell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho-associated protein kinase (ROCK), LIM-Kinase (LIMK), and cofilin. Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. In this study, we discovered that PRP4 over-expression in HCT116 colon cancer cells induces cofilin dephosphorylation by inhibiting the Rho-ROCK-LIMK-cofilin pathway. Two-dimensional gel electrophoresis, and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4 transfected HCT116 cells. The presence of PRP4 increased the expression of PP1A both at the mRNA and protein levels, which possibly activated cofilin through dephosphorylation and subsequently modulated the cell actin cytoskeleton. Furthermore, we found that PRP4 over-expression did not induce cofilin dephosphorylation in the presence of okadaic acid, a potent phosphatase inhibitor. Moreover, we discovered that PRP4 over-expression in HCT116 cells induced dephosphorylation of migration and invasion inhibitory protein (MIIP), and down-regulation of E-cadherin protein levels, which were further restored by the presence of okadaic acid. These findings indicate a possible molecular mechanism of PRP4-induced actin cytoskeleton remodeling and epithelial mesenchymal transition, and make PRP4 an important target in colon cancer. PMID- 29787736 TI - G-quadruplexes in the BAP1 promoter positively regulate its expression. AB - Accumulating evidence suggests a key role of BAP1 in oncogenesis, but mechanisms regulating BAP1 gene expression remain unexplored. In this report, we revealed that the BAP1 promoter contains multiple G-tracts in its negative strand with high potential of forming G-quadruplex (G4) structures. In circular dichroism studies, synthesized oligonucleotides within these G-rich regions upstream the BAP1 transcription start site showed molar ellipticity at specific wavelengths characteristic of G4 structures. Analyses of these oligonucleotides by native polyacrylamide gel electrophoresis revealed formation of multiple types of G4 structures. In reporter assays, mutations or deletion of predicted G4 structures reduced BAP1 promoter activity. Additionally, DNA helicases CHD2 and CHD7 could reduce BAP1 promoter activity, likely through unwinding its G4 structures. PMID- 29787738 TI - Altered brain activity during withdrawal from chronic alcohol is associated with changes in IL-6 signal transduction and GABAergic mechanisms in transgenic mice with increased astrocyte expression of IL-6. AB - Interleukin-6 (IL-6) is an important neuroimmune factor that is increased in the brain by alcohol exposure/withdrawal and is thought to play a role in the actions of alcohol on the brain. To gain insight into IL-6/alcohol/withdrawal interactions and how these interactions affect the brain, we are studying the effects of chronic binge alcohol exposure on transgenic mice that express elevated levels of IL-6 in the brain due to increased astrocyte expression (IL-6 tg) and their non-transgenic (non-tg) littermate controls. IL 6/alcohol/withdrawal interactions were identified by genotypic differences in spontaneous brain activity in electroencephalogram (EEG) recordings from the mice, and by Western blot analysis of protein activation or expression in hippocampus obtained from the mice after the final alcohol withdrawal period. Results from EEG studies showed frequency dependent genotypic differences in brain activity during withdrawal. For EEG frequencies that were affected by alcohol exposure/withdrawal in both genotypes, the nature of the effect was similar, but differed across withdrawal cycles. Differences between IL-6 tg and non-tg mice were also observed in Western blot studies of the activated form of STAT3 (phosphoSTAT3), a signal transduction partner of IL-6, and subunits of GABAA receptors (GABAAR). Regression analysis revealed that pSTAT3 played a more prominent role during withdrawal in the IL-6 tg mice than in the non-tg mice, and that the role of GABAAR alpha-5 and GABAAR alpha-1 in brain activity varied across genotype and withdrawal. Taken together, our results suggest that IL-6 can significantly impact mechanisms involved in alcohol withdrawal. PMID- 29787737 TI - Resistance training attenuates inflammation and the progression of renal fibrosis in chronic renal disease. AB - Patients with chronic kidney disease (CKD) have progressive renal fibrosis, inflammation, and reduced muscle mass and strength. Resistance training (RT) has been suggested to mitigate the loss of muscle mass, of strength and the inflammation in CKD, but the mechanisms are unknown. The aim of this study was to evaluate the influence of RT on renal fibrosis, renal cytokine expression, creatine kinase levels, and muscle mass and strength in CKD rats. A CKD model was obtained by 5/6 nephrectomy (Nx). Fifteen 8-week-old male rats were divided into 3 groups: Sham (control), Nx SED (CKD sedentary) and Nx RT (CKD trained). The RT consisted of ladder climbing at 70% of the animal's maximal carrying capacity for 10 weeks. Muscle strength, creatine kinase levels, renal fibrosis and mRNA interleukin (IL)-4, IL-6 and IL-10 were analyzed after the RT protocol. There was significant improvement in the muscle strength and creatine kinase levels in the Nx RT group. Moreover, renal fibrosis and inflammation were attenuated, with increased IL-4 and IL-10 expression and reduced IL-6 expression in the Nx RT group compared with that in the Nx SED group. No difference in muscle mass was observed among the groups. In conclusion, RT was effective in reducing fibrosis and inflammation, in addition to increasing muscle strength and creatine kinase levels, in rats with CKD, independent of muscle mass. PMID- 29787739 TI - Apathy in individuals with Parkinson's disease associated with mild cognitive impairment. A neuropsychological investigation. AB - Apathy is frequently reported in individuals with Parkinson's disease (PD) and is hypothesized to be associated with frontal-striatal related cognitive functions. Available data, however, do not provide univocal results. Moreover, this relationship has been poorly investigated in PD patients with mild cognitive impairment (MCI). This study was aimed at investigating the association between severity of apathy of PD patients and their performance on neuropsychological tests investigating executive abilities. Individuals with PD (i.e., with and without MCI) and healthy controls (HCs) were administered a neuropsychological test battery that investigated episodic memory, language, short-term memory and attention, visual-spatial abilities and executive functions. Subjects were also administered additional neuropsychological tests to evaluate the different executive subcomponents (i.e., planning/abstract reasoning, self monitoring/response inhibition, working memory, shifting and fluency). The Apathy Evaluation Scale (AES) was administered to assess apathy severity. Linear regression analyses were applied to the data; results showed that in the PD group with MCI, the best cognitive factor associated to the AES score was patients' scores on the executive tests and, in particular, their scores on tests examining planning/abstract reasoning. By contrast, in the PD group without MCI, the cognitive performance was not significantly associated to apathy severity. Findings of the study document a specific association between reduced efficiency of the executive system and apathy severity in individuals with PD and MCI. This association indirectly supports the hypothesis of a relationship between motivational disorders and dysregulation of the activity of the frontal-striatal networks in PD patients. PMID- 29787740 TI - Conservative Management Following Complete Clinical Response to Neoadjuvant Chemotherapy of Muscle Invasive Bladder Cancer: Contemporary Outcomes of a Multi Institutional Cohort Study. AB - PURPOSE: We report the outcomes in patients with muscle invasive bladder cancer from 2 institutions who experienced a clinically complete response to neoadjuvant platinum based chemotherapy and elected active surveillance. It was unknown whether conservative treatment could be safely implemented in these patients. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with muscle invasive bladder cancer at our institutions who elected surveillance following a clinically complete response to transurethral resection of bladder tumors and neoadjuvant chemotherapy from 2001 to 2017. A clinically complete response was defined as absent tumor on post-chemotherapy transurethral resection of bladder tumor, negative cytology and normal cross-sectional imaging. RESULTS: In the 148 patients followed a median of 55 months (range 5 to 145) the 5-year disease specific, overall, cystectomy-free and recurrence-free survival rates were 90%, 86%, 76% and 64%, respectively. Of the patients 71 (48%) experienced recurrence in the bladder, including 16 (11%) with muscle invasive disease and 55 (37%) with noninvasive disease. Salvage radical cystectomy prevented cancer specific death in 9 of 12 patients (75%) who underwent cystectomy after muscle invasive relapse and in 13 of 14 (93%) after noninvasive relapse. CONCLUSIONS: We observed high rates of overall and disease specific survival with bladder preservation in patients who achieved a clinically complete response to neoadjuvant chemotherapy. These outcomes support the safety of active surveillance in carefully selected, closely monitored patients with muscle invasive bladder cancer. Future studies should aim to improve patient selection by identifying biomarkers predicting invasive relapse and developing novel imaging methods of early detection. PMID- 29787741 TI - The prognostic value of long noncoding RNA Sox2ot expression in various cancers: A systematic review and meta-analysis. AB - BACKGROUND: Several investigations have explored the prognostic value of long noncoding RNA Sox2 overlapping transcript (lncRNA Sox2ot) expression in human cancers, however, with inconsistent results. The aim of this study was to evaluate the prognostic role of lncRNA Sox2ot expression in various cancers. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched to retrieve relevant studies. The relationships between lncRNA Sox2ot expression and prognostic parameters were detected, including overall survival (OS), tumor differentiation, clinical stage, distant metastasis, lymph node metastasis and so on. RESULTS: A total of 10 studies involving 943 cancer patients were finally included into the study. High lncRNA Sox2ot expression was significantly related to shorter OS in cancers (HR = 2.06, 95%CI = 1.67-2.55, P < 0.01). The cancer patients with high lncRNA Sox2ot expression tended to have worse tumor differentiation (P = 0.04), advanced clinical stage (P < 0.01), earlier distant metastasis (P < 0.01), and earlier lymph node metastasis (P = 0.01) compared to those with low lncRNA Sox2ot expression. However, there was no distinct correlation between lncRNA Sox2ot expression and age (P = 0.87), gender (P = 0.48), tumor size (P = 0.08), or vascular invasion (P = 0.07). CONCLUSION: High lncRNA Sox2ot expression was significantly associated with worse OS, advanced clinical stage, worse tumor differentiation, earlier distant metastasis, and earlier lymph node metastasis in various cancers. LncRNA Sox2ot expression might a promising prognostic factor in various cancers. PMID- 29787742 TI - Hidden sites in the distribution of the crayfish plague pathogen Aphanomyces astaci in Eastern Europe: Relicts of genetic groups from older outbreaks? AB - The crayfish plague agent Aphanomyces astaci is one of the world's most threatening invasive species. Originally from North America, the pathogen is being imported alongside American crayfish species, which are used for various purposes. In this study, we investigated the marginal, currently known distribution area of the pathogen in Eastern Europe by sampling narrow-clawed crayfish (Astacus leptodactylus) and spiny-cheek crayfish (Orconectes limosus) populations. In addition, using specific real-time PCR, we tested several marine decapod species, which also occur in brackish waters of the Danube at the West coast of the Black Sea and the Dniester River basin. By sequencing the nuclear chitinase gene, mitochondrial rnnS/rnnL DNA and by genotyping using microsatellite markers, we identified the A. astaci haplogroups of highly infected specimens. The A. astaci DNA was detected in 9% of the investigated A. leptodactylus samples, both in invaded and non-invaded sectors, and in 8% of the studied O. limosus samples. None of the marine decapods tested positive for A. astaci. The results revealed that narrow-clawed crayfish from the Dniester River carried the A. astaci B-haplogroup, while A. astaci from the Danube Delta belonged to the A- and B-haplogroups. In the invaded sector of the Danube, we also identified the A-haplogroup. Microsatellite analysis revealed a genotype identical to the genotype Up. It might be that some of the detected A. astaci haplogroups are relics from older outbreaks in the late 19th century, which may have persisted as a chronic infection for several decades in crayfish populations. PMID- 29787743 TI - Persistence of Central Venous Oxygen Desaturation During Early Sepsis Is Associated With Higher Mortality: A Retrospective Analysis of the ALBIOS Trial. AB - BACKGROUND: Relevance of low (< 70%) central venous oxygen saturation (ScvO2) during early sepsis has been recently questioned by three negative trials (Protocol-Based Care for Early Septic Shock, Australasian Resuscitation in Sepsis Evaluation, and Protocolized Management in Sepsis) on early goal-directed therapy; however, subjects included in those trials had ScvO2 at enrollment as high as 71 +/- 13%, 73 +/- 11%, and 70 +/- 12%. Here we assess the association between ScvO2 < 70% at 6 h and 90-day mortality in subjects enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial, focusing on those with initial ScvO2 < 70%. METHODS: Regardless of treatment assignment (to receive albumin or not), all subjects enrolled in the ALBIOS trial received early goal-directed therapy aiming for ScvO2 >= 70% at 6 h. Using multivariable logistic regression analyses, we tested the association between ScvO2 < 70% at 6 h and 90-day mortality in those with initial ScvO2 < 70% (n = 514) or >= 70% (n = 961). RESULTS: ScvO2 < 70% at 6 h was independently associated with higher 90-day mortality in subjects with initial ScvO2 < 70% (OR, 1.84; 95% CI, 1.19-2.85; P = .007) but not in those with initial ScvO2 >= 70% (OR, 1.25; 95% CI, 0.79-1.95; P = .357). ScvO2 < 70% at enrollment and at 6 h was associated with history and/or signs of cardiac dysfunction but not with greater severity of disease or more aggressive resuscitation (required per protocol). CONCLUSIONS: In the ALBIOS trial, persistence of low ScvO2 was associated with higher 90-day mortality, possibly because it reflected underlying cardiac dysfunction. Subjects with ScvO2 < 70% may benefit most from individually tailored interventions aimed at normalizing the balance between systemic oxygen delivery and consumption. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00707122; URL: www.clinicaltrials.gov. PMID- 29787745 TI - Modeling transposable element dynamics with fragmentation equations. AB - Transposable elements (TEs), segments of DNA capable of self-replication, are abundant in the genomes of most organisms and thus serve as a record of past mutational events. While some work suggests TEs may serve a regulatory function for the host, most empirical and theoretical studies have shown that TEs often have deleterious effects on a host. Because they are not essential, the host genome consists of both full-length (actively replicating) and partial length (inactive remnant) copies of TEs. We developed a novel mathematical formulation of TE dynamics by modeling the density of full and partial length copies resulting from mutations (insertions and deletions) and TE replication within the host genome. More specifically, we model the time-evolution of the complete TE length distribution (full and partial elements) in a genome using fragmentation equations in both a discrete and continuous framework under two models of TE replication. In the first case, we assume that full-length TEs replicate at a constant rate regardless of the number of full-length TEs present in the genome. While this assumption simplifies the underlying biological processes, it allows us to derive an explicit analytical form of the time-varying TE density, as well as the steady-state behavior, under both discrete and continuous formulations. Next, we take into account the potential deleterious effects of TEs by modeling TE replication with a logistic growth equation. Under this assumption, the number of actively replicating TEs in a genome is limited by a carrying capacity. While we are still able to derive to derive analytical forms for the time-varying TE density, for both discrete and continuous length formulations, these solutions are implicit. For all four proposed models, we prove existence and uniqueness of these solutions describing TE length distributions. We compare both models and note that the logistic and exponential models initially agree. Since most TEs have not reached carrying capacity, we use the explicit exponential solution to quantify rates of replication to mutations. We apply our model to present day annotated collections of TEs from the genomes of species of fruit-flies, birds, and primates to uncover quantitative relationships of TE dynamics. With the increasing availability of complete genomes, our method is likely to uncover relationships of biological drivers of genomic variation in many species. PMID- 29787746 TI - Two-photon microscopy of fungal keratitis-affected rabbit cornea ex vivo using moxifloxacin as a labeling agent. AB - Two-photon microscopy (TPM) is a three dimensional (3D) microscopic technique based on nonlinear two-photon fluorescence, which has been tested as an alternative to reflectance confocal microscopy (RCM) for detecting fungal keratitis via optical imaging. Although TPM provided images with better contrast than RCM for fungal keratitis, its imaging speed was relatively low because of weak intrinsic signal. Moxifloxacin, a Food and Drug Administration (FDA) approved antibiotic, was recently used as a cell-labeling agent for TPM. In this study, moxifloxacin was used to label fungal cells for TPM imaging of fungal keratitis models. Fungal cell suspensions and ex vivo fungal keratitis-affected rabbit corneas were prepared using two types of fungal pathogens, Aspergillus fumigatus and Candida albicans, and TPM imaging was performed both with and without moxifloxacin treatment. Fungal cells with enhanced fluorescence were clearly visible by TPM of moxifloxacin-treated fungal cell suspensions. TPM of moxifloxacin-treated fungal keratitis rabbit corneas revealed both the infecting fungal cells and corneal cells similar to those observed in TPM without moxifloxacin treatment, albeit with approximately 10-times enhanced fluorescence. Fungal cells were distinguished from corneal cells on the basis of their distinct morphologies. Thus, TPM with moxifloxacin labeling might be useful for the detection of fungal keratitis at the improved imaging speed. PMID- 29787744 TI - Repression of MAP3K1 expression and JNK activity by canonical Wnt signaling. AB - Morphogenesis is a complex and highly coordinated process orchestrated by temporal spatial activity of developmental pathways. How the different pathways interact to guide the developmental program remains an intriguing and open question. MAP3K1-JNK and Wnt are signaling pathways crucial for embryonic eyelid closure, an epithelial morphogenetic event conserved in mammals. Here we used a mouse model of eyelid development and genetic and biochemistry tools to investigate the relationships between the two pathways. We found that Wnt activation repressed MAP3K1 expression. Using Axin-LacZ reporter mice, spatial Wnt activity was detected in the leading edge of the developing eyelid. Conditional knockout of Wntless (Wls) in ocular surface ectoderm blocked eyelid formation, and significantly increased MAP3K1 expression in eyelid cells at the nasal canthus region. Conversely, knockout of Dkk2, encoding a canonical Wnt antagonist, resulted in an increase of Wnt activity in cells at the upper eyelid margin near the nasal canthus. Up-regulation of Wnt signaling in the Dkk2 knockout embryos corresponded to down-regulation of MAP3K1 expression. In vitro data showed that Wnt3a treatment decreased MAP3K1 promoter activity, whereas activation of Wnt by lithium chloride inhibited MAP3K1 expression, and attenuated MAP3K1-mediated JNK activity. Our data identify a unique signal crosstalk between Wnt signaling and the MAP3K1-JNK pathway in epithelial morphogenesis. PMID- 29787747 TI - Spatially explicit approach to estimation of total population abundance in field surveys. AB - Population abundance is fundamental in ecology and conservation biology, and provides essential information for predicting population dynamics and implementing conservation actions. While a range of approaches have been proposed to estimate population abundance based on existing data, data deficiency is ubiquitous. When information is deficient, a population estimation will rely on labor intensive field surveys. Typically, time is one of the critical constraints in conservation, and management decisions must often be made quickly under a data deficient situation. Hence, it is important to acquire a theoretical justification for survey methods to meet a required estimation precision. There is no such theory available in a spatially explicit context, while spatial considerations are critical to any field survey. Here, we develop a spatially explicit theory for population estimation that allows us to examine the estimation precision under different survey designs and individual distribution patterns (e.g. random/clustered sampling and individual distribution). We demonstrate that clustered sampling decreases the estimation precision when individuals form clusters, while sampling designs do not affect the estimation accuracy when individuals are distributed randomly. Regardless of individual distribution, the estimation precision becomes higher with increasing total population abundance and the sampled fraction. These insights provide theoretical bases for efficient field survey designs in information deficiency situations. PMID- 29787748 TI - Vitamin D Receptor Is Required for Proliferation, Migration, and Differentiation of Epidermal Stem Cells and Progeny during Cutaneous Wound Repair. AB - Epidermal stem cells residing in the skin play an essential role in epidermal regeneration. When skin is injured, the stem cells are first activated to proliferate, and subsequently the progeny migrate and differentiate to regenerate the epidermis. Here, we demonstrate that the vitamin D receptor (VDR) is essential for these processes to occur. The requirement for VDR on epidermal stem cell function was revealed in conditional VDR knockout mice, in which VDR was deleted from stem cells and progeny, and mice were maintained on a low calcium diet. First, self-renewal and niche formation of epidermal stem cells were impaired. Wound-induced activation of epidermal stem cells was blunted associated with a reduction of beta-catenin signaling. Second, wound induced migration of stem cells and progeny was impaired as shown by lineage tracing and delayed migration of VDR silenced cells. Epidermal differentiation of progeny was impaired at the wounding site associated with reduced E-cadherin expression. Deletion of VDR also changed stem cell fate blunting hair development, increasing sebaceous glands, and altering expression and location of epidermal markers. These results suggest that VDR is required for self-renewal, migration, and differentiation of epidermal stem cells and progeny during cutaneous wound healing. PMID- 29787749 TI - Epidermal HMGB1 Activates Dermal Fibroblasts and Causes Hypertrophic Scar Formation in Reduced Hydration. AB - HMGB1 protein is a multifunctional cytokine involved in inflammatory reactions and is known to play a key role in tissue repair and fibrosis. However, the function of HMGB1 in fibrotic skin diseases, such as hypertrophic scar formation, remains unclear. In this study, HMGB1 was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, we found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts. HMGB1 secreted from keratinocytes activated fibroblasts by promoting the nuclear import of MRTF-A, increased the nuclear accumulation of MRTF-A/SRF complexes and consequently enhanced alpha-smooth muscle actin promoter activation. Moreover, blockade of advanced glycation end products or Toll-like receptor 2/4 inhibited the fibroblast activation induced by HMGB1. Finally, local delivery of HMGB1 resulted in marked hypertrophic scar formation in rabbit hypertrophic scar models, while HMGB1 blockade exerted a clear anti-scarring effect. Our results indicate that high HMGB1 levels induced by a reduced hydration status play an important role in hypertrophic scar formation, strongly suggesting that HMGB1 is a novel target for preventing scarring. PMID- 29787750 TI - Erybraedin A is a potential Src inhibitor that blocks the adhesion and viability of non-small-cell lung cancer cells. AB - The adhesion of cancer cells to the extracellular matrix (ECM) is crucial for cell proliferation, survival, and metastasis. Thus, it is necessary to inhibit cell-ECM adhesion by blocking the activation of the associated signaling to control cancer. Here, we identify erybraedin A (EBA) as a potential Src inhibitor that blocks cell adhesion and viability in non-small-cell lung cancer (NSCLC). EBA significantly inhibited the adhesion of NSCLC cells to fibronectin. EBA also markedly inhibited the activation of Src and its downstream targets, including FAK and Akt. The interaction between integrin beta1 or integrin beta3 and Src was inhibited by EBA treatment. A docking study revealed the bindings of EBA to the ATP-binding pocket and the allosteric regulatory site of the Src kinase. Additionally, EBA markedly inhibited the viability and the colony formation of NSCLC cells and induced apoptotic cell death. These results describe novel biological properties of EBA, which can block the Src-mediated adhesion and survival of NSCLC cells, suggesting the potential of EBA as an anticancer Src inhibitor that warrants further development in advanced preclinical and clinical settings. PMID- 29787753 TI - miR-193a inhibits osteogenic differentiation of bone marrow-derived stroma cell via targeting HMGB1. AB - BACKGROUND: miR-193a has been shown to be involved in a variety of biological processes, including cell proliferation, differentiation, and apoptosis. However, little is known about how miR-193a regulates osteogenic differentiation. METHODS: We employed RT-qPCR to determine the level of miR-193a and mRNA level of HMGB1 and osteoblast-specific markers (Runx2, ALP, OSX, OCN). Besides, westernblot was used to probe protein level of phosphorylated MAPK family members and beta catenin. Bioinformatic analysis was used to predict the putative binding sequence of miR-193a to the 3'-UTR of HMGB1 and we confirmed this result by dual luciferase reporter assay. Alizarin red staining assay (ARS) and alkaline phosphatase activity (ALP) were performed to detect osteogenic differentiation. RESULTS: miR-193a was downregulated in OM (osteogenic medium)induced hBMSC. More interestingly, we found that miR-193a mimic attenuated matrix mineralization and alkaline phosphatase activity, whereas miR-193a inhibitor exerted the opposite phenotypes. Mechanistically, we observed that miR-193a played an inhibitory role in expression of osteoblast-specific markers and activation of MAPK and Wnt signaling pathways. Bioinformatic analysis and dual luciferase assay demonstrated that miR-193a directly targeted 3'-UTR of HMGB1. Furthermore, we overexpressed HMGB1 in miR-193a overexpressed hBMSC to establish that HMGB1 acted as downstream target of miR-193a-inhibited osteogenic differentiation. CONCLUSIONS: Here, we reveal miR-193a plays a suppressive role in osteogenic differentiation of hBMSC via targeting HMGB1. These findings provide a novel mechanism underlying osteogenic differentiation and offer therapeutical strategy for bone formation. PMID- 29787751 TI - The N-terminal domain of gastrulation brain homeobox 2 (Gbx2) is required for iridophore specification in zebrafish. AB - Although body color pattern formation by pigment cells plays critical roles in animals, pigment cell specification has not yet been fully elucidated. In zebrafish, there are three chromatophores: melanophore, iridophore, and xanthophore, that are derived from neural crest cells (NCCs). A recent study has reported the differentially expressed genes between melanophores and iridophores. Based on transcriptome data, we identified that Gbx2 is required for iridophore specification during development. In support of this, iridophore formation is suppressed by gbx2 knockdown by morpholino antisense oligonucleotide, at 72 h post fertilization (hpf) in zebrafish. Moreover, gbx2 is expressed in sox10 expressing NCCs and guanine crystal plates-containing iridophores during development at 24 and 48 hpf, respectively. In gbx2 knockdown zebrafish embryos, apoptosis of sox10-expressing NCCs was detected at 24 hpf without any effect on the formation of melanophores and xanthophores at 48 hpf. We further observed that the N-terminal domain of Gbx2 is able to rescue the iridophore formation defect caused by gbx2 knockdown. Our study provides insights into the requirement of N-terminal domain of Gbx2 for iridophore specification in zebrafish. PMID- 29787752 TI - Systemic inhibition of Janus kinase induces browning of white adipose tissue and ameliorates obesity-related metabolic disorders. AB - Browning of white adipose tissue is a promising strategy to tackle obesity. Recently, Janus kinase (JAK) inhibition was shown to induce white-to-brown metabolic conversion of adipocytes in vitro; however effects of JAK inhibition on browning and systemic metabolic health in vivo remain to be elucidated. Here, we report that systemic administration of JAK inhibitor (JAKi) ameliorated obesity related metabolic disorders. Administration of JAKi in mice fed a high-fat diet increased UCP-1 and PRDM16 expression in white adipose tissue, indicating the browning of white adipocyte. Food intake was increased in JAKi-treated mice, while the body weight and adiposity was similar between the JAKi- and vehicle treated mice. In consistent with the browning, thermogenic capacity was enhanced in mice treated with JAKi. Chronic inflammation in white adipose tissue was not ameliorated by JAKi-treatment. Nevertheless, insulin sensitivity was well preserved in JAKi-treated mice comparing with that in vehicle-treated mice. Serum levels of triglyceride and free fatty acid were significantly reduced by JAKi treatment, which is accompanied by ameliorated hepatosteatosis. Our data demonstrate that systemic administration of JAKi has beneficial effects in preserving metabolic health, and thus inhibition of JAK signaling has therapeutic potential for the treatment of obesity and its-related metabolic disorders. PMID- 29787754 TI - Different players generate positive responses in two in vitro cytokine assay formats with aqueous and immobilized TGN1412 analog. AB - To detect potential risk of severe cytokine release syndrome, in vitro assay formats with human cells have been developed. The two major testing platforms are a combination of whole blood with aqueous-phase test articles (whole blood cytokine assay, WBCA) and peripheral blood mononuclear cells with solid-phase articles (PBMC assay). Significant induction of cytokines was seen in both assays after treatment with a widely used control agent, TGN1412 or its analog CD28SA, but the WBCA cytokine profile differed from what was expected from clinical experience. In the WBCA, potential risk of CD28SA was detected by elevation of IL 8 whereas IL-2, a key cytokine after stimulation of CD28, was not induced in approximately 40% of donor samples. Therefore, further mechanistic understanding of the different responses in the in vitro assay was needed. In this study of donor samples treated with CD28SA, we compared the induction of cytokines and identified the cytokine-producing cells in the two assays. IL-2 was markedly elevated in all the donors in the PBMC assay but only in 1 of 3 donors in the WBCA. IL-8, the most sensitive biomarker in the WBCA, was produced by monocytes and granulocytes. T cells, the most relevant player in the PBMC assay with CD28SA, did not contribute to the positive response seen in two donors in the WBCA, which suggests that different players caused the positive cytokine responses to CD28SA in the two assays. PMID- 29787755 TI - Vibsanin A sensitizes human acute myeloid leukemia cells to tyrosine kinase inhibitor-induced myeloid differentiation via activation of PKC and upregulation of Lyn. AB - Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy. PMID- 29787757 TI - Dlx2 overexpression enhanced accumulation of type II collagen and aggrecan by inhibiting MMP13 expression in mice chondrocytes. AB - Genetic studies revealed a crucial role of Distal-homebox (Dlx) genes in skeletal development, and our previous study demonstrated overexpressing Dlx2 in neural crest cells led to abnormal cartilage structure, including ectopic cartilage in the maxillary region and nasal bone in mice. The aim of this study was to investigate how Dlx2 overexpression affects chondrogenesis in mouse chondroblast cell line TMC23 and the underlying mechanism. We first demonstrated that Dlx2 expression was upregulated during chondrogenesis in TMC23 cells. Moreover, forced overexpression of Dlx2 in TMC23 cells led to increased accumulation of aggrecan and type II collagen, markers of early chondrocyte differentiation, but had little effect on mRNA and protein levels of Aggrecan and Col2alpha1, type II collagen gene. Importantly, Dlx2 overexpression decreased mRNA and protein levels of MMP13, a major collagenase degrading aggrecan and type II collagen during late stages of chondrogenesis. Luciferase-reporter and Chromatin-immunoprecipitation analysis demonstrated that MMP13 promoter contained two Dlx2-response elements, and Dlx2 inhibited MMP13 expression by directly binding to these two elements. Based on these observations, we propose that forced overexpression of Dlx2 enhances early chondrocyte differentiation by increasing accumulation of type II collagen and aggrecan, but interferes later stages of chondrocyte differentiation through inhibiting MMP13 expression. PMID- 29787756 TI - Fibronectin Type III Domain Containing 4 attenuates hyperlipidemia-induced insulin resistance via suppression of inflammation and ER stress through HO-1 expression in adipocytes. AB - Although Fibronectin Type III Domain Containing 4 (FNDC4) has been reported to be involved in the modulation of inflammation in macrophages, its effects on inflammation and insulin resistance in adipose tissue are unknown. In the current study, we investigated the effects of FNDC4 on hyperlipidemia-mediated endoplasmic reticulum (ER) stress, inflammation, and insulin resistance in adipocytes via the AMP-activated protein kinase (AMPK)/heme oxygenase-1 (HO-1) mediated pathway. Hyperlipidemia-induced nuclear factor kappaB (NFkappaB), inhibitory kappaBalpha (IkappaBalpha) phosphorylation, and pro-inflammatory cytokines such as TNFalpha and MCP-1 were markedly mitigated by FNDC4. Furthermore, FNDC4 treatment attenuated impaired insulin signaling in palmitate treated differentiated 3T3-L1 cells and in subcutaneous adipose tissue of HFD-fed mice. FNDC4 administration ameliorated glucose intolerance and reduced HFD induced body weight gain in mice. However, FNDC4 treatment did not affect calorie intake. Additionally, treatment with FNDC4 attenuated hyperlipidemia-induced phosphorylation or expression of ER stress markers such as IRE-1, eIF2alpha, and CHOP in 3T3-L1 adipocytes and in subcutaneous adipose tissue of mice. FNDC4 treatment stimulated AMPK phosphorylation and HO-1 expression in 3T3-L1 adipocytes and in subcutaneous adipose tissue of mice. siRNA-mediated suppression of AMPK and HO-1 abrogated the suppressive effects of FNDC4 on palmitate-induced ER stress, inflammation, and insulin resistance. In conclusion, our results show that FNDC4 ameliorates insulin resistance via AMPK/HO-1-mediated suppression of inflammation and ER stress, indicating that FNDC4 may be a novel therapeutic agent for treating insulin resistance and type 2 diabetes. PMID- 29787758 TI - Tissue factor mediates microvesicles shedding from MDA-MB-231 breast cancer cells. AB - Extracellular vesicles, such as microvesicles (MVs), were identified as important players in tumor progression and acquisition of an aggressive phenotype. Tissue factor (TF) is a transmembrane protein that initiates the blood coagulation cascade. In tumor cells, TF has been associated with aggressiveness and cancer progression. Previous studies demonstrate that TF is incorporated into MVs secreted by tumor cells; however, it is unknown whether TF is actively involved in the release of MVs. Here, we investigated the influence of TF expression on the release of MVs. TF silencing was achieved through CRISPR/Cas9 approaches in the human breast cancer cell line, MDA-MB-231. TF knockout in MDA-MB-231 cells efficiently reduced TF-dependent signaling and procoagulant activity. Remarkably, silencing of TF caused a significant decrease in the number of MVs released by MDA-MB-231 cells. We also observed an increase in actin-positive membrane projections in TF knockout cells and a reduction in RhoA expression when compared to TF-expressing cells. Treatment of MDA-MB-231 cells with the RhoA-ROCK signaling pathway inhibitor, fasudil, significantly reduced the release of MVs. Taken together, our results suggest a novel and relevant role for TF in tumor biology by playing an active role in the MVs secretion. PMID- 29787759 TI - Glycosylation status of nicastrin influences catalytic activity and substrate preference of gamma-secretase. AB - gamma-Secretase complex, the assembly of nicastrin (NCT), Presenilin (PS), Presenilin Enhancer-2 (PEN-2) and Anterior pharynx defective 1 (Aph-1), catalyzes the cleavage of amyloid precursor protein to generate amyloid-beta protein (Abeta), the main culprit of Alzheimer's disease. NCT becomes matured through complex glycosylation and play important role in gamma-secretase activity by interacting with catalytic subunit PS. However, the role of NCT glycosylation on gamma-secretase activity and substrate specificity is still unknown. The purpose of this study is to investigate the effect of NCT glycosylation on gamma secretase activity and substrate specificity in a group of glycosylation mutant lectin resistant CHO (Lec) cells. CHO Lec-1 cells lack glycosyltransferase-I, GnT I, thus N-glycan on NCT are all oligomannose type, whereas CHO Lec-2 cells synthesize NCT containing sialic acid deficient oligosaccharides due to the impairment of cytidine 5'-monophosphate-sialic acid transporter. Here, we reported that mutant CHO Lec-1 and Lec-2 reduced gamma-secretase activity in both cell-based and biochemical assays, and that CHO Lec-1 preferentially reduced Abeta generation. Endogenous level of gamma-secretase complex, subcellular distribution of gamma-secretase subunits and the level of functional gamma secretase complex remained unchanged in mutants. Interestingly, Coimmunoprecipitation study revealed that mutant gamma-secretase could recognize substrate as well as parental gamma-secretase. Our data suggests that thorough glycosylation of NCT is critical for enzymatic activity and substrate preference of gamma-secretase. PMID- 29787760 TI - In vivo gene correction with targeted sequence substitution through microhomology mediated end joining. AB - Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo. Our method could realize more efficient sequence substitution than the HDR-based method in vitro using a reporter cell line, and led to the survival of a hereditary tyrosinemia mouse model in vivo. The proposed MMEJ-based TSS approach could provide a novel therapeutic strategy, in addition to HDR, to achieve gene correction from a mutated sequence to a normal sequence. PMID- 29787761 TI - Biophysical studies and modelling indicate the binding preference of TAZ WW domain for LATS1 PPxY motif. AB - The Hippo tumor suppressor pathway is an important regulator of cell proliferation and apoptosis, and signal transduction occurs through phosphorylation of the effector protein TAZ by the serine/threonine kinase LATS1/2. Here, we report the biophysical and computational studies to characterize the interaction between TAZ and LATS1/2 through WW domain-PPxY motif binding. We show that the TAZ WW domain exhibits a binding preference for the second of the two PPxY motifs of LATS1 in vitro. We modelled the structure of the domain in complex with LATS1 PPxY2 peptide and, through molecular dynamics simulations, show that WW domain-PPxY2 complex is stable with some flexibility in the peptide region. Next, we predict and verify that L143 and T150 of the WW domain are important for TAZ binding with the PPxY2 peptide using mutational and isothermal titration calorimetric studies. Furthermore, we suggest that the electrostatic potential of charged residues within the binding pocket may influence the ligand affinity among otherwise highly similar WW domains. PMID- 29787762 TI - Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood brain barrier. AB - Exosomes are nano-vesicles released by tumor cells to modulate extracellular environment. Accumulating evidence revealed that glioblastoma derived exosomes contain multiple pro-angiogenic factors to induce the proliferation of endothelial cells. Here, we investigated the role of GBM-derived exosomes in inducing the permeability of the blood-brain barrier. We found that VEGF-A was over-expressed in hypoxic GBM-derived exosomes, which enhance the permeability of a BBB in vitro model by interrupting the expression of claudin-5 and occludin. In vivo permeability assay showed hypoxic GBM-derived exosomes remained functional in the blood circulation and induced the permeability of BBB. PMID- 29787763 TI - The TORC1 signaling pathway regulates respiration-induced mitophagy in yeast. AB - Mitophagy is an evolutionarily conserved autophagy process that selectively degrades mitochondria. This catabolic event is considered to be a mitochondrial quality control system crucial for cell homeostasis, however, mechanisms regulating mitophagy remain largely unknown. Here we show that the TORC1 (target of rapamycin complex 1) signaling pathway regulates mitophagy in budding yeast via SEACIT (Seh1-associated complex inhibiting TORC1) consisting of Iml1, Npr2, and Npr3. Cells lacking SEACIT displayed significant reductions in mitophagy during prolonged respiratory growth, while the other selective autophagy processes are less affected. Under the same conditions, mitophagy defects were strikingly rescued in the SEACIT mutants (1) treated with rapamycin, a specific TOR kinase inhibitor, (2) lacking Gtr1, a TORC1-stimulating Rag family GTPase downstream of SEACIT, and (3) devoid of Pib2, a phosphatidylinositol 3-phosphate binding TORC1 activator. Notably, loss of Npr2 exacerbated mitophagy defects in cells lacking Atg13, a TORC1 effector crucial for activation of autophagy-related processes, suggesting additional mitophagy-specific regulator(s) downstream of TORC1. Finally, we found that npr2-null cells failed to stabilize the interaction of Atg32 with Atg11, a scaffold protein essential for mitophagy. Collectively, our data implicate SEACIT-mediated inactivation of TORC1 signaling as a critical step to promote respiration-induced mitophagy. PMID- 29787764 TI - APOBEC3B Nuclear Localization Requires Two Distinct N-Terminal Domain Surfaces. AB - The APOBEC3 family of cytosine deaminases catalyzes the conversion of cytosines to-uracils in single-stranded DNA. Traditionally, these enzymes are associated with antiviral immunity and restriction of DNA-based pathogens. However, a role for these enzymes in tumor evolution and metastatic disease has also become evident. The primary APOBEC3 candidate in cancer mutagenesis is APOBEC3B (A3B) for three reasons: (1) A3B mRNA is upregulated in several different cancers, (2) A3B expression and mutational loads correlate with poor clinical outcomes, and (3) A3B is the only family member known to be constitutively nuclear. Previous studies have mapped non-canonical A3B nuclear localization determinants to a single surface-exposed patch within the N-terminal domain (NTD). Here, we show that A3B has an additional, distinct, surface-exposed NTD region that contributes to nuclear localization. Disruption of residues within the first 30 amino acids of A3B (import surface 1) or loop 5/alpha-helix 3 (import surface 2) completely abolish nuclear localization. These import determinants also graft into NTDs of related family members and mediate re-localization from cell-wide-to-nucleus or cytoplasm-to-nucleus. These findings demonstrate that both sets of residues are required for non-canonical A3B nuclear localization and describe unique surfaces that may serve as novel therapeutic targets. PMID- 29787765 TI - Using Single-Molecule Approaches to Understand the Molecular Mechanisms of Heat Shock Protein Chaperone Function. AB - The heat-shock proteins (Hsp) are a family of molecular chaperones, which collectively form a network that is critical for the maintenance of protein homeostasis. Traditional ensemble-based measurements have provided a wealth of knowledge on the function of individual Hsps and the Hsp network; however, such techniques are limited in their ability to resolve the heterogeneous, dynamic and transient interactions that molecular chaperones make with their client proteins. Single-molecule techniques have emerged as a powerful tool to study dynamic biological systems, as they enable rare and transient populations to be identified that would usually be masked in ensemble measurements. Thus, single molecule techniques are particularly amenable for the study of Hsps and have begun to be used to reveal novel mechanistic details of their function. In this review, we discuss the current understanding of the chaperone action of Hsps and how gaps in the field can be addressed using single-molecule methods. Specifically, this review focuses on the ATP-independent small Hsps and the broader Hsp network and describes how these dynamic systems are amenable to single-molecule techniques. PMID- 29787766 TI - Structure and Functional Characterization of Human Histidine Triad Nucleotide Binding Protein 1 Mutations Associated with Inherited Axonal Neuropathy with Neuromyotonia. AB - Inherited peripheral neuropathies are a group of neurodegenerative disorders that clinically affect 1 in 2500 individuals. Recently, genetic mutations in human histidine nucleotide-binding protein 1 (hHint1) have been strongly and most frequently associated with patients suffering from axonal neuropathy with neuromyotonia. However, the correlation between the impact of these mutations on the hHint1 structure, enzymatic activity and in vivo function has remained ambiguous. Here, we provide detailed biochemical characterization of a set of these hHint1 mutations. Our findings indicate that half of the mutations (R37P, G93D and W123*) resulted in a destabilization of the dimeric state and a significant decrease in catalytic activity and HINT1 inhibitor binding affinity. The H112N mutant was found to be dimeric, but devoid of catalytic activity, due to the loss of the catalytically essential histidine; nevertheless, it exhibited high affinity to AMP and a HINT1 inhibitor. In contrast to the active-site mutants, the catalytic activity and dimeric structure of the surface mutants, C84R and G89V, were found to be similar to the wild-type enzyme. Taken together, our results suggest that the pathophysiology of inherited axonal neuropathy with neuromyotonia can be induced by conversion of HINT1 from a homodimer to monomer, by modification of select surface residues or by a significant reduction of the enzyme's catalytic efficiency. PMID- 29787769 TI - Elevating Integrin-linked Kinase expression has rescued hippocampal neurogenesis and memory deficits in an AD animal model. AB - Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3beta pathway. Finally, we found that Fluoxetine, a selective serotonin reuptake inhibitor, could improve the impaired hippocampal neurogenesis and memory by enhancing ILK AKT-GSK3beta pathway activity in APP/PS1 mice. Thus, these findings demonstrated the effects of ILK on neurogenesis and memory recovery, suggesting that ILK is an important therapeutic target for AD prevention and treatment. PMID- 29787767 TI - Influence of gag and RRE Sequences on HIV-1 RNA Packaging Signal Structure and Function. AB - The packaging signal (Psi) and Rev-responsive element (RRE) enable unspliced HIV 1 RNAs' export from the nucleus and packaging into virions. For some retroviruses, engrafting Psi onto a heterologous RNA is sufficient to direct encapsidation. In contrast, HIV-1 RNA packaging requires 5' leader Psi elements plus poorly defined additional features. We previously defined minimal 5' leader sequences competitive with intact Psi for HIV-1 packaging, and here examined the potential roles of additional downstream elements. The findings confirmed that together, HIV-1 5' leader Psi sequences plus a nuclear export element are sufficient to specify packaging. However, RNAs trafficked using a heterologous export element did not compete well with RNAs using HIV-1's RRE. Furthermore, some RNA additions to well-packaged minimal vectors rendered them packaging defective. These defects were rescued by extending gag sequences in their native context. To understand these packaging defects' causes, in vitro dimerization properties of RNAs containing minimal packaging elements were compared to RNAs with sequence extensions that were or were not compatible with packaging. In vitro dimerization was found to correlate with packaging phenotypes, suggesting that HIV-1 evolved to prevent 5' leader residues' base pairing with downstream residues and misfolding of the packaging signal. Our findings explain why gag sequences have been implicated in packaging and show that RRE's packaging contributions appear more specific than nuclear export alone. Paired with recent work showing that sequences upstream of Psi can dictate RNA folds, the current work explains how genetic context of minimal packaging elements contributes to HIV-1 RNA fate determination. PMID- 29787768 TI - The angiotensin II type I receptor antagonist losartan retards amygdala kindling induced epileptogenesis. AB - Blood-brain barrier (BBB) breakdown and the subsequent exposure of the cerebral cortex to serum albumin are known to activate transforming growth factor beta (TGF-beta) signaling in astrocytes and to play key roles in epileptogenesis after brain injury. It was recently reported that the angiotensin II type I receptor antagonist losartan suppresses activation of TGF-beta signaling and prevents epileptogenesis in a rat vascular injury model. Here, we investigated the effects of losartan on epileptogenesis following amygdala kindling in rats. Systemic or intracerebroventricular (i.c.v.) administration of losartan significantly delayed the development of severe behavioral seizures and stimulus-induced seizures on EEG (afterdischarge) in the early stage of amygdala kindling, as assessed by electroencephalography. Losartan also significantly increased the number of stimulations required to reach the fully kindled state. However, losartan had no effects on the threshold for afterdischarge induction, the afterdischarge duration, or seizure severity in fully kindled rats. Evaluation of BBB permeability by Evans blue staining did not indicate BBB breakdown (extravasation of serum albumin) in any region of the brain in the fully kindled animals. Thus, losartan may be useful in preventing epileptogenesis, even in post brain-insult epilepsy, in the absence of BBB breakdown. PMID- 29787770 TI - Lateral hypothalamic orexin glucose-inhibited neurons may regulate reward-based feeding by modulating glutamate transmission in the ventral tegmental area. AB - Glucose inhibits ~60% of lateral hypothalamic (LH) orexin neurons. Fasting increases the activation of LH orexin glucose-inhibited (GI) neurons in low glucose. Increases in spontaneous glutamate excitatory postsynaptic currents (sEPSCs) onto putative VTA DA neurons in low glucose are orexin dependent (Sheng et al., 2014). VTA DA neurons modulate reward-based feeding. We tested the hypothesis that increased activation of LH orexin-GI neurons in low glucose increases glutamate signaling onto VTA DA neurons and contributes to reward-based feeding in food restricted animals. N-methyl-D-aspartate (NMDA) and alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents on putative VTA DA neurons were measured using whole cell voltage clamp recording in horizontal brain slices containing the LH and VTA. Decreased glucose increased the NMDA receptor current for at least one hour after returning glucose to basal levels (P < 0.05; N = 8). The increased current was blocked by an orexin 1 receptor antagonist (P < 0.05; N = 5). Low glucose caused a similar persistent enhancement of AMPA receptor currents (P < 0.05; N = 7). An overnight fast increased the AMPA/NMDA receptor current ratio, an in vivo index of glutamate plasticity, on putative VTA DA neurons. Conditioned place preference (CPP) for palatable food was measured during LH dialysis with glucose. CPP score was negatively correlated with increasing LH glucose (P < 0.05; N = 20). These data suggest that increased activation of LH orexin-GI neurons in low glucose after weight loss, leads to enhanced glutamate signaling on VTA DA neurons, increases the drive to eat rewarding food, and may contribute to weight regain. PMID- 29787771 TI - Inhibition of PTEN protects PC12 cells against oxygen-glucose deprivation induced cell death through mitoprotection. AB - Mitochondria involve in the determination of ischemic neuronal cell fate through regulation of apoptotic and necrotic cell death. Phosphatase and tensin homolog (PTEN) protein negatively regulates Akt/PKB signaling which is the major cell survival pathway. The current study aimed to examine the impact of SF1670, a potent PTEN inhibitor, on mitochondria-mediated cell survival pathways in an in vitro stroke-like model. PC12 cells were exposed to one hour oxygen and glucose deprivation (OGD) followed by different time points of reperfusion (0, 30, 60, 120 and 180 min) and SF1670 treatments. Our findings showed that OGD/R exposure increased reactive oxygen species (ROS) levels, reduced phosphorylated Akt (p Akt), ratios of Bcl-2/BAX, intracellular ATP, mitochondrial vital activity and mitochondrial membrane potential (Deltapsim). OGD/R exposure also increased cleaved caspase 3/pro-caspase 3 and cleaved caspase 9/pro-caspase 9 ratios associated with low cell viability, high lactate dehydrogenase (LDH) release, and greater apoptotic cell death in the TUNEL assay. Conversely, inhibition of PTEN by SF1670 were associated with increased expression of p-Akt and anti-apoptotic proteins (Bcl-2), attenuated pro-apoptotic proteins (BAX) and oxidative stress index (ROS), improved mitochondrial function (restored MMP and ATP), and decreased apoptotic cell death. These results strongly suggest that neuroprotective effect of SF1670 against OGD/R-induced cell death at least is partially mediated through mitoprotective properties of SF1670. PMID- 29787772 TI - Ginkgolide K promotes astrocyte proliferation and migration after oxygen-glucose deprivation via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway. AB - Ischemic stroke is the leading cause of death around the world. Ginkgolide K (GK) has been used to treat ischemic stroke due to its neuroprotective potential. However, the molecular mechanism underlying the neuroprotective effect of GK in ischemic stroke is still almost blank. In this study, astrocytes were divided into four groups: control group, oxygen-glucose deprivation (OGD) group, OGD + GK group and OGD + GK + Compound C (CC) group. The viability and proliferation of astrocytes were examined by Cell Counting Kit-8 assay and 5-ethynyl-20 deoxyuridine (EdU) assay, respectively. Transwell migration and wound scratch assays were conducted to evaluate astrocyte migration. The protein expression in astrocytes were determined by western blot assay. We found that GK pretreatment promoted astrocyte proliferation and migration after OGD as shown by the increase in the viability of astrocytes, glial fibrillary acidic protein level, the number of EdU positive cells and migrated cells, and the migration distance. GK pretreatment induced autophagy after OGD, as indicated by upregulation of autophagy-related protein 7, Beclin-1 protein and increase of microtubule associated protein 1 light chain 3 (LC3)-II/LC3-I, and downregulation of p62 protein. Moreover, GK pretreatment activated the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (m-TOR)/ULK1 pathway in astrocytes following OGD. Notably, CC treatment blocked the promotory effect of GK on astrocyte proliferation and migration after OGD. Collectively, GK promoted astrocyte proliferation and migration after OGD via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway. Our findings suggested that GK might be a potential agent for cerebral ischemia/reperfusion injury. PMID- 29787773 TI - An optimized dose of raspberry ketones controls hyperlipidemia and insulin resistance in male obese rats: Effect on adipose tissue expression of adipocytokines and Aquaporin 7. AB - Obesity constitutes a major worldwide problem in which hyperlipidemia and insulin resistance represents adverse metabolic consequences of it. The present study was conducted to elucidate the role of raspberry ketones (RKs) in controlling body weight gain, hyperlipidemia and insulin resistance in male obese rats through affecting the expression of various adipocytokines. As Aquaporin-7 is co-related with the expression of various adipocytokines and has recently emerged as a modulator of adipocyte metabolism, the present study evaluated the effect of RKs on adipose tissue expression of aquaporin-7(AQP7) in high-fat (HF) diet-fed rats. Groups of male rats were assigned to normal, HF diet-fed control rats and RKs treated (250 and 500 mg/kg) groups. RKs administration effectively abrogated hyperlipidemia and oxidative burden and enhanced insulin sensitivity. In addition, treatment with RKs ameliorated adipose tissue and liver indices and the reduced adipocyte diameters. Moreover, administration of the low dose of RKs ameliorated the expression of apelin and its receptor, and visfatin with upregulating adiponectin expression compared to HF diet control rats. However, both doses effectively downregulated leptin expression. It was obvious that both RKs doses revealed effectiveness in upregulating the AQP7 expression. The present data suggest the promising therapeutic role of RKs in HF diet-induced obesity that is likely attributable, at least in part, to upregulation of AQP7 expression. PMID- 29787774 TI - Silencing of PAQR3 suppresses extracellular matrix accumulation in high glucose stimulated human glomerular mesangial cells via PI3K/AKT signaling pathway. AB - Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism. Our results demonstrated that HG significantly up-regulated the expression of PAQR3 in human MCs. In addition, knockdown of PAQR3 efficiently suppressed MC proliferation and ECM production in HG-stimulated MCs. Furthermore, knockdown of PAQR3 markedly reversed HG-induced PI3K/AKT activation in MCs. In summary, our present study demonstrated that knockdown of PAQR3 suppressed HG-induced the proliferation and ECM accumulation in human MCs, via inhibiting the PI3K/AKT signaling pathway. Thus, PAQR3 may be a potential therapeutic target for the treatment of diabetic nephropathy. PMID- 29787775 TI - Health information exposure from information and communication technologies and its associations with health behaviors: Population-based survey. AB - Health information and communication technologies (ICTs) are increasingly used but little is known about routine exposure to health information from ICTs and its associations with health behaviors. A territory-wide population-based dual landline and mobile telephone survey was conducted in 2016 in Hong Kong, where smartphone ownership and Internet access are among the most prevalent, easiest and fastest in the world. Health information exposure from traditional sources (television/radio/newspaper/magazine), Internet websites, social media sites and instant messaging (IM); and information on smoking, alcohol consumption and physical activity were recorded. Prevalence was weighted by age, sex and education level of the general population. Multinomial logistic regression was used to assess the association of health information exposure with smoking and alcohol consumption, whilst multivariable linear regression was used to assess the association with frequency of moderate and vigorous physical activity (days/week). Of 3063 respondents, most (71.6%) were often or sometimes exposed to health information from traditional sources, followed by Internet websites (40.9%), social media sites (40.7%), and IM (27.0%). Respondents with lower education and household income were less frequently exposed to health information from Internet websites, social media sites and IM (all P < 0.001). Health information exposure from IM was associated with being never smokers, and more frequent moderate and vigorous physical activity (all P for trend <0.05). Health information exposure from IM was least frequent but associated with healthier behaviors. Further public health education campaigns can consider using IM to deliver information, particularly to disadvantaged groups. PMID- 29787776 TI - Intraepidermal nerve fibres are not the exclusive tranducers of nociception. AB - The goal of this article is to provide an insight of the most recent data on cutaneous nociception. Indeed recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intraepidermal free nerve endings are not exclusive transducers of pain. Therefore, the results of neurophysiological studies should be interpreted in the light of this information. PMID- 29787777 TI - Examination of the effects of cannabinoid ligands on decision making in a rat gambling task. AB - Although exposure to delta-9-tetrahydrocannabinol (THC) is perceived to be relatively harmless, mounting evidence has begun to show that it is associated with a variety of cognitive deficits, including poor decision making. THC-induced impairments in decision making are thought to be the result of cannabinoid CB1 receptor activation, and although clinical literature suggests that chronic activation via THC contributes to perturbations in decision making, acute CB1 receptor modulation has yielded mixed results. Using an animal model to examine how CB1-specific ligands impact choice biases would provide significant insight as to how recruitment of the endocannabinoid system may influence decision making. Here, we used the rat gambling task (rGT), a validated analogue of the human Iowa Gambling Task, to assess baseline decision making preferences in male Wistar rats. After acquisition rGT performance was measured. Animals were challenged with the CB1 receptor antagonist rimonabant, the partial agonist THC, and the synthetic agonist WIN55,212-2. Animals were also treated acutely with the fatty acid amide hydrolase (FAAH) inhibitor URB597 to selectively upregulate the endocannabinoid anandamide. Blockade of the CB1 receptor produced a trend improvement in decision making in animals who preferred the advantageous task options, yet left choice unaffected in risk-prone rats. Neither CB1 receptor agonist had strong effects on decision making, but a high dose THC decreased premature responses, whereas WIN55,212-2 did the opposite. URB597 did not affect task performance. These results indicate that although chronic CB1 receptor activation may be associated with impaired decision making, acute modulation has modest effects on choice and instead may play a substantive role in regulating impulsive responding. PMID- 29787778 TI - Monoclonal antibodies against loggerhead sea turtle, Caretta caretta, IgY isoforms reveal differential contributions to antibody titers and relatedness among other sea turtles. AB - Serum from loggerhead sea turtles, Caretta caretta, was collected from the southeast Atlantic Ocean during routine summer monitoring studies in 2017. Serum immunoglobulin IgY was purified and used to develop IgY isoform-specific monoclonal antibodies (mAb). mAb LH12 was developed against the 66 kDa heavy chain of IgY, mAb LH1 was developed against the truncated heavy chain of approximately 37 kDA, and mAb LH9 was developed against the 23 kDa light chains. mAb LH9 reacts with the light chains of all sea turtles, mAb LH12 reacts with the long heavy chain of all sea turtles within the family Cheloniidae, and mAb LH1 reacts with the truncated form of IgY in both olive and Kemp's ridley turtles. Circulating IgY antibodies against three different marine bacterial pathogens were determined in 16 loggerhead samples using these mAbs. mAb LH12 detects higher titers than mAb LH1, and mAb LH9 detects the highest titers. PMID- 29787779 TI - Stichodactyla helianthus' de novo transcriptome assembly: Discovery of a new actinoporin isoform. AB - Transcriptomic profiling of venom producing tissues from different animals is an effective approach for discovering new toxins useful in biotechnological and pharmaceutical applications, as well in evolutionary comparative studies of venomous animals. Stichodactyla helianthus is a Caribbean sea anemone which produces actinoporins as part of its toxic venom. This family of pore forming toxins is multigenic and at least two different isoforms, encoded by separate genes, are produced by S. helianthus. These isoforms, sticholysins I and II, share 93% amino acid identity but differ in their pore forming activity and act synergistically. This observation suggests that other actinoporin isoforms, if present in the venomous mixture, could offer an advantageous strategy to modulate whole venom activity. Using high-throughput sequencing we generated a de novo transcriptome of S. helianthus and determined the relative expression of assembled transcripts using RNA-Seq to better characterize components of this species' venom, focusing on actinoporin diversity. Applying this approach, we have discovered at least one new actinoporin variant from S. helianthus in addition to several other putative venom components. PMID- 29787780 TI - Association of ST2 polymorphisms with atopy, asthma, and leukemia. PMID- 29787781 TI - Regulation of bile secretion by calcium signaling in health and disease. AB - Calcium (Ca2+) signaling controls secretion in many types of cells and tissues. In the liver, Ca2+ regulates secretion in both hepatocytes, which are responsible for primary formation of bile, and cholangiocytes, which line the biliary tree and further condition the bile before it is secreted. Cholestatic liver diseases, which are characterized by impaired bile secretion, may result from impaired Ca2+ signaling mechanisms in either hepatocytes or cholangiocytes. This review will discuss the Ca2+ signaling machinery and mechanisms responsible for regulation of secretion in both hepatocytes and cholangiocytes, and the pathophysiological changes in Ca2+ signaling that can occur in each of these cell types to result in cholestasis. PMID- 29787782 TI - Effect of desensitizing toothpastes on dentine hypersensitivity: A systematic review and meta-analysis. AB - OBJECTIVES: To evaluate the desensitizing effect of toothpastes that contain ingredients that act against dentine hypersensitivity (DH) and to compare this effect with negative controls. SOURCES: Five databases were searched to identify relevant articles published up to November 27, 2017. STUDY SELECTION: Randomized controlled trials (RCTs) comparing desensitizing toothpastes with a toothpastes without desensitizing component in adult patients that suffer from DH were included. The risk of bias was assessed according to the Cochrane guidelines, and the quality of the evidence was evaluated using the GRADE tool. Inverse variance random-effects meta-analyses of standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated using RevMan 5.3 software. DATA: 53 RCTs with 4796 patients were finally included in the meta-analysis. The toothpastes that contain active desensitization ingredients showed a better desensitizing effect on DH than the negative control, except the strontium- and amorphous calcium phosphate-containing toothpastes. The amorphous calcium phosphate-containing toothpaste had very low-quality evidence, the strontium, potassium and strontium, and potassium and stannous fluoride-containing toothpastes had low-quality evidence, and the other five toothpastes had moderate quality evidence. CONCLUSIONS: Our result support the premise that toothpastes containing potassium, stannous fluoride, potassium and strontium, potassium and stannous fluoride, calcium sodium phosphosilicate, arginine, and nano hydroxyapatite relieve the symptoms of DH, but does not advise the use of toothpastes that contain strontium and amorphous calcium phosphate. Furthermore, high-quality studies are needed to confirm our results. (PROSPERO CRD42018085639). PMID- 29787783 TI - Segmentation of the rabies virus genome. AB - We established a system for the recovery of a segmented recombinant rabies virus, the virus genome RNA of which was divided into two parts: segment 1 encoding the nucleoprotein, phosphoprotein, matrix protein, and glycoprotein genes, and segment 2 encoding the large RNA-dependent RNA polymerase gene. The morphology of the segmented recombinant rabies virus was bullet-like in shape with a length of approximately 130 nm, which is shorter than the 200-nm long non-segmented recombinant rabies virus. The segmented recombinant rabies virus was maintained for at least 18 passages. The virus multiplication rate of the segmented recombinant rabies virus was lower than that of the non-segmented recombinant rabies virus during the passages, and the relative amounts of virus genome RNAs for segment 1 and segment 2 differed in the supernatant of the segmented recombinant rabies virus infected cells. These results suggest that the segmented recombinant rabies virus packages either segment 1 or segment 2 into each virus particle. Thus, co-infection with segmented recombinant rabies virus particles packaging segment 1 or segment 2 may be necessary for the production of progeny virus. PMID- 29787784 TI - Heart rate variability response to affective pictures processed in and outside of conscious awareness: Three consecutive studies on emotional regulation. AB - Previous research has increased understanding of the neurobiological basis of emotional regulation. However, less is known concerning the unconscious processing of affective information. Three experiments were performed to investigate the extent to which complex affective stimuli can be processed outside of consciousness and demonstrate possible mechanisms for regulation of resulting emotional responses. In Experiment 1, participants were either instructed to passively observe blocked-picture cues (neutral and negative) or to downregulate their emotions by distancing. Resulting emotional regulation activity was assessed with 0.1-Hz heart rate variability (HRV) indices. In Experiment 2, participants were presented with affective pictures that were rendered consciously invisible by means of continuous flash suppression (CFS). In Experiment 3, two equivalent sets of negative affective pictures were covertly presented and the effect of a cognitive task on emotional regulation was evaluated. Our findings revealed that 0.1-Hz HRV indices exhibited greater change over baseline in response to negative compared to neutral stimuli for both presentation conditions (consciously perceived or not). The implementation of distancing and the cognitive task were both associated with higher 0.1-Hz HRV change scores. These results indicate that even complex affective stimuli can be processed without awareness, resulting in a congruent emotional response that is physiologically detectable. Cognitive strategies can help more effectively regulate this response, implying that conscious perception of a triggering stimulus may not be essential for cognitive regulation. PMID- 29787786 TI - Preparation of 99mTc-levetiracetam intranasal microemulsion as the first radiotracer for SPECT imaging of the Synaptic Vesicle Protein SV2A. AB - Selective receptors imaging using gamma emitting radiopharmaceuticals allows accurate diagnosis and follow up of many brain related disorders. Levetiracetam, a selective SV2A receptor antiepileptic, was successfully radiolabeled using 99mTc. Different conditions affecting the labelling process were studied and optimum radiochemical yield of 89.8% was obtained. 99mTc-levetiracetam was effectively formulated and characterized as microemulsion with particle size of 16.34 +/- 5.58 nm and polydispersity index of 0.382 +/- 0.05. Parallel biodistribution studies were performed comparing brain targeting efficiency of I.V 99mTc-levetiracetam solution, I.N 99mTc-levetiracetam solution and I.N 99mTc levetiracetam microemulsion. Brain radioactivity uptake and brain/blood uptake ratio for I.N 99mTc-levetiracetam microemulsion were higher than the other two routes at all time intervals. Such results present intranasal 99mTc-levetiracetam microemulsion as the first SPECT tracer for imaging SV2A receptor. PMID- 29787785 TI - Junior temperament character inventory together with quantitative EEG discriminate children with attention deficit hyperactivity disorder combined subtype from children with attention deficit hyperactivity disorder combined subtype plus oppositional defiant disorder. AB - Oppositional defiant disorder (ODD) is frequently associated with Attention Deficit Hyperactivity Disorder (ADHD) but no clear neurophysiological evidence exists that distinguishes the two groups. Our aim was to identify biomarkers that distinguish children with Attention Deficit Hyperactivity Disorder combined subtype (ADHD_C) from children with ADHD_C + ODD, by combining the results of quantitative EEG (qEEG) and the Junior Temperament Character Inventory (JTCI). 28 ADHD_C and 22 ADHD_C + ODD children who met the DSMV criteria participated in the study. JTCI and EEG were analyzed. Stability based Biomarkers identification methodology was applied to the JTCI and the qEEG separately and combined. The qEEG was tested at the scalp and the sources levels. The classification power of the selected biomarkers was tested with a robust ROC technique. The best discriminant power was obtained when TCI and qEEG were analyzed together. Novelty seeking, self-directedness and cooperativeness were selected as biomarkers together with F4 and Cz in Delta; Fz and F4 in Theta and F7 and F8 in Beta, with a robust AUC of 0.95 for the ROC. At sources level: the regions were the right lateral and medial orbito-frontal cortex, cingular region, angular gyrus, right inferior occipital gyrus, occipital pole and the left insula in Theta, Alpha and Beta. The robust estimate of the total AUC was 0.91. These structures are part of extensive networks of novelty seeking, self-directedness and cooperativeness systems that seem dysregulated in these children. These methods represent an original approach to associate differences of personality and behavior to specific neuronal systems and subsystems. PMID- 29787787 TI - The antidepressant-like effect of galanin in the dorsal raphe nucleus of rats involves GAL2 receptors. AB - Galanin is a neuropeptide distributed in human and rat brain regions that are involved with emotional regulation, such as the dorsal raphe nucleus (DRN). Galanin effects in the DRN are mediated by GAL1 and GAL2 receptors. Intracerebral infusion of a GAL2 (AR-M1896) or a GAL1 (M617) agonist induced either antidepressant or depressive-like effect, respectively, in rats exposed to the forced swimming test (FST). However, it is not clear if GAL1 and/or GAL2 receptors present in the DRN would be involved in such effects. Therefore, we investigated the effects induced by intra-DRN infusion of galanin (0.3 nmol), AR M1896 (1 nmol, GAL2 agonist), or M617 (GAL1 agonist) in rats exposed to the FST. Galanin and AR-M1896 intra-DRN administration induced antidepressant-like effect in the FST. However, M617 did not induce any change in the FST. Neither M617 nor AR-M1896 changed the locomotor activity of rats in the open field test. Intra-DRN pre-treatment with M871 (1 nmol), a selective GAL2 antagonist, counteracted the antidepressant-like effect induced by galanin. These results suggest that galanin signaling through GAL2 receptors in the DRN produces triggers antidepressant-like effect. PMID- 29787788 TI - Increases in motor cortical excitability during mirror visual feedback of a precision grasp is influenced by vision and movement of the opposite limb. AB - Unimanual grasp movements with mirrored visual feedback (MVF) can improve function and increase excitability of primary motor cortex (M1) ipsilateral to the moving hand. However, no study to date has examined the contribution of vision and movement of the opposite hand during an object-directed precision grasp. In this study, we tested 15 healthy individuals in three conditions: MVF (vision + motor), Movement (motor component), and Action Observation (vision component). We hypothesized that unimanual grasp movements with MVF increases the excitability and reduces intracortical inhibition of the M1 ipsilateral to the moving hand. We found increased excitability in the right primary motor cortex (M1) ipsilateral to the moving right hand for MVF movements compared to Rest (Baseline). In contrast, no change was found in right M1 with only movement of the right hand or observation of object-directed precision grasp with left hand. We also found a reduction in short-interval intracortical inhibition in MVF movements compared to baseline. These findings suggest that excitability in M1 during an object-directed precision grasp is mediated by the combination of viewing the movement performed and performing the movement from the opposite hand. PMID- 29787789 TI - The cognitive up- and down-regulation of positive emotion: Evidence from behavior, electrophysiology, and neuroimaging. AB - Although numerous studies have investigated emotion regulation, the physiological responses and neural substrates of positive emotion regulation remain unclear. To address this question, we explored the effect of reappraisal on subjective experience, zygomatic electromyography (zEMG) response, and blood oxygen level response, using the same materials across three independent experiments. Behaviorally, up-regulating positive emotion increased the valence, arousal, and zEMG response, whereas down-regulating positive emotion decreased the valence, but not arousal or the zEMG response. The neuroimaging results indicate that reappraisal-related prefrontal and cingulate regions were recruited in both the up- and down-regulation conditions, while the bilateral occipital lobe was more active in the up-regulation than in the down-regulation. The psychophysiological interaction analysis revealed that the prefrontal-subcortical (amygdala and ventral striatal) connections were primarily recruited during up-regulation. This study expands the research on emotion regulation and enhances the understanding of the mechanisms underlying the cognitive regulation of positive emotion. PMID- 29787790 TI - A discriminative test among the different theories proposed to explain the origin of the genetic code: The coevolution theory finds additional support. AB - A discriminative statistical test among the different theories proposed to explain the origin of the genetic code is presented. Gathering the amino acids into polarity and biosynthetic classes that are the first expression of the physicochemical theory of the origin of the genetic code and the second expression of the coevolution theory, these classes are utilized in the Fisher's exact test to establish their significance within the genetic code table. Linking to the rows and columns of the genetic code of probabilities that express the statistical significance of these classes, I have finally been in the condition to be able to calculate a chi2 value to link to both the physicochemical theory and to the coevolution theory that would express the corroboration level referred to these theories. The comparison between these two chi2 values showed that the coevolution theory is able to explain - in this strictly empirical analysis - the origin of the genetic code better than that of the physicochemical theory. PMID- 29787791 TI - Pathogen-dependent modulation of milk neutrophils competence, plasma inflammatory cytokines and milk quality during intramammary infection of Sahiwal (Bos indicus) cows. AB - The aim of the current study was to investigate the responses of milk neutrophils and plasma inflammatory cytokines to various mastitis pathogens and subsequently on milk composition. Milk was collected from healthy (n = 10) and clinical mastitis indigenous Sahiwal cows naturally infected either with gram-positive bacteria mainly S. aureus (n = 10) and Strep. agalactiae (n = 10) or with gram negative bacteria, E. coli (n = 10). Phagocytic activity of milk neutrophils decreased in all mastitis cows with the lowest values recorded during gram positive bacterial infections. Maximum plasma cortisol levels were observed in cows infected with gram-positive bacteria and were positively correlated with the milk neutrophils percentage and negatively correlated with the phagocytic activity of neutrophils and expression of glucocorticoid receptor. The plasma concentrations of IL-2 and IL-8 increased in all mastitis groups with maximum values recorded during E. coli infections. Unlike gram-negative bacterial infections, gram-positive bacterial infections evoked a minimal tumor necrosis factor-alpha (TNF-alpha), and IL-6 response. Milk somatic cell counts, fat, protein, pH and electrical conductivity increased in mastitis cows with the highest values exhibited by Strep. agalactiae infection. The expression of chemokine receptors (CXCR1, CXCR2), IL-8 and CD11b was maximum in mastitis neutrophils infected with E. coli. The expression of glucocorticoid receptor (GRalpha) decreased in all mastitis groups with the lowest values were found in S. aureus infection. Among the various mastitis pathogens, Strep. agalactiae showed maximum adverse effect on milk quality. Attenuated neutrophils, TNF-alpha and IL-6 response in cows infected by gram-positive bacteria may contribute to the establishment of chronic mastitis. PMID- 29787792 TI - Age-dependent alterations in expression and co-localization of Pax6 and Ras-GAP in brain of aging mice. AB - As the brain ages, the survival and plasticity of neurons and glia are compromised. The data-mining and in silico studies suggest interactions of Pax6 with Ras and binding sites in Ras-GAP promoter. The Pax6 also shows age-dependent alterations. Therefore, it is presumed that Pax6 may be associated with the Ras GAP, a synaptic protein, either directly or indirectly in brain. The expression, co-localization and interaction of Pax6 and Ras-GAP in different regions of brain of mice during aging were investigated through immunofluorescence assay, co immunoprecipitation and western blotting, respectively. The co-localization of Pax6 and Ras-GAP were observed in dentate gyrus (DG) and sub-granular zone (SGZ) of hippocampus, in glomerular (GlLa) and mitral cells (MiCe) of olfactory lobe, granular cells (GrCe), Purkinje cell (PuCe) and molecular cell layer (MoLa) of cerebellum, internal plexiform layer (InPl), molecular layer (MoLa) of cerebral cortex and in intercalated cells of amygdala (ITC), caudate nucleus regions in brain of aging mice. The expression of Pax6 and Ras-GAP was altered in hippocampus, amygdala, caudate nucleus, olfactory lobe, cerebral cortex and cerebellum from young to old mice. The Pax6 interacts with Ras-GAP in brain of mice. Results indicate impact of Pax6 on Ras-GAP-mediated activities of synapses, learning and memory, emotions and fear as well as motor functions. Alterations in expression and co-localization of Pax6 and Ras-GAP during aging may be responsible for age-associated compromised survival and plasticity of neurons and glia. PMID- 29787793 TI - Chlorogenic acid ameliorates alcohol-induced liver injuries through scavenging reactive oxygen species. AB - The key role of oxidative stress in alcoholic liver disease (ALD) has been established by the large body of evidence from previous studies. Excessive consumption of ethanol induces the production of a variety of reactive oxygen species (ROS) in the liver, such as superoxide, H2O2, and hydroxyl radical. These products activate oxidant-sensitive signaling cascades and modulators of apoptosis. Because ROS accumulation is closely related to ALD, a number of studies have investigated the benefits of antioxidants. Recent studies demonstrated that polyphenol chlorogenic acid (CGA) has antioxidant properties and health benefits, such as reduction of relative risk of cardiovascular diseases and hepatoprotective effects against acetaminophen toxicity. However, the protective effects of CGA against ALD have not been studied in detail. We hypothesize that CGA plays a role in preventing ALD through its antioxidant properties. In this study, we investigated the protective effects of CGA against liver injuries in vivo. Reduced alcohol-induced-steatosis, apoptotic cell death, and fibrosis due to reduced levels of oxidative stress were observed. These findings suggest that CGA treatment can be an effective approach to attenuate ALD through the suppression of oxidative stress. PMID- 29787794 TI - Early growth response gene 1 is essential for urban particulate matter-induced inflammation and mucus hyperproduction in airway epithelium. AB - Particulate matter (PM) has been implicated as a risk factor for human airway disorders. However, the biological mechanisms underlying the correlation between PM exposure and adverse airway effects have not yet been fully clarified. The objective of this study was to explore the possible role of early growth response gene 1 (Egr-1) in PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction in vitro and in vivo. Particulate matter exposure induced a rapid Egr-1 expression in human bronchial epithelial (HBE) cells and in mouse lungs. Genetic blockage of Egr-1 markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells, and these effects were mechanistically mediated by the nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) pathways, respectively. Egr-1-knockout mice displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Moreover, polycyclic aromatic hydrocarbons (PAHs) contained in the PM also induced Egr-1 expression, and also played a role in the inflammatory responses and mucus production. Taken together, our data reveal novel Egr-1 signaling that mediates the NF-kappaB and AP-1 pathways to orchestrate PM-induced pulmonary inflammation and mucus hyperproduction, suggesting that Egr-1 inhibition could be an effective therapeutic approach for airway disorders or disease exacerbations induced by airborne particulate pollution. PMID- 29787796 TI - Prediction of poor neurological outcome within 24 h from cardiac arrest: Can electrophysiology-based indices be helpful? PMID- 29787795 TI - Anti-allergy and anti-tussive activity of Clitoria ternatea L. in experimental animals. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower. AIM OF THE STUDY: Ethanolic extract of Clitoria ternatea flowers (ECT) was evaluated for its anti-allergy and anti-tussive potential in experimental animals. Additionally, the anti-inflammatory potential of ECT was carried out to draw a plausible mechanism of action of the drug. MATERIALS AND METHODS: In-vitro anti-asthmatic activity of ECT was evaluated in goat tracheal chain and isolated guinea pig ileum preparations. Acute and chronic anti asthmatic activity of ECT (100, 200 and 400 mg/kg; p.o.) was estimated in histamine aerosol exposed guinea pigs and in OVA sensitized and challenged mice respectively. Anti-tussive activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against sulfur dioxide- and citric acid-induced cough in experimental animals. Moreover, the anti-inflammatory activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against carrageenan- and acetic acid-induced inflammation in rats. RESULTS: ECT attenuated histamine-induced contraction in both goat tracheal chain and isolated guinea pig ileum preparations. ECT (400 mg/kg) attenuated histamine-induced dyspnoea and OVA-induced changes in differential cell count in broncheoalveolar fluid, levels of interleukins (IL-1beta and IL-6) and immunoglobulin (OVA-sensitive IgG1) in animals. ECT (400 mg/kg) further ameliorated sulfur dioxide- and citric acid-induced cough in experimental animals. Additionally, ECT (400 mg/kg) attenuated inflammation in carrageenan and acetic acid challenged rodents. CONCLUSIONS: Standardized ECT could be considered as a potential therapeutic alternative in the management of allergy-induced asthma. PMID- 29787797 TI - Developing neurites from mouse basal forebrain gonadotropin-releasing hormone neurons use Sonic hedgehog to modulate their growth. AB - Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are required for fertility in all mammalian species studied to date. GnRH neuron cell bodies reside in the basal forebrain, and most extend long neurites in the caudal direction to terminate at the median eminence (ME), the site of hormone secretion. Using in vitro neurite growth assays, histological methods, and genetic deletion strategies in mice we have analysed the role of the morphogen and neurite growth and guidance molecule, Sonic hedgehog (Shh), in the growth of GnRH neurites to their target. Immunohistochemistry revealed that Shh was present in the basal forebrain, the preoptic area (POA) and mediobasal hypothalamus (MBH) at gestational day 14.5 (GD 14.5), a time when GnRH neurites grow towards the ME. Furthermore, in situ hybridization revealed that mRNA encoding the Shh receptor, Smoothened (Smo), was present in GnRH neurons from GD 15.5, when the first GnRH neurites are extending towards the MBH. In vitro neurite growth assays using hypothalamic explants from GD 15.5 fetuses in 3-D collagen gels showed that Shh was able to significantly stimulate GnRH neurite outgrowth. Finally, genetic deletion of Smo specifically from GnRH neurons in vivo, using Cre-loxP technology, resulted in a significant decrease in GnRH neurites innervating the ME. These experiments demonstrate that GnRH neurites use Shh for their neurite development, provide further understanding of the mechanisms by which GnRH nerve terminals arrive at their site of hormone secretion, and identify an additional hypothalamic neuronal population for which Shh/Smo signaling is developmentally important. PMID- 29787798 TI - Comprehensive analysis of a metabolic model for lipid production in Rhodosporidium toruloides. AB - The yeast Rhodosporidium toruloides has been extensively studied for its application in biolipid production. The knowledge of its metabolism capabilities and the application of constraint-based flux analysis methodology provide useful information for process prediction and optimization. The accuracy of the resulting predictions is highly dependent on metabolic models. A metabolic reconstruction for R. toruloides metabolism has been recently published. On the basis of this model, we developed a curated version that unblocks the central nitrogen metabolism and, in addition, completes charge and mass balances in some reactions neglected in the former model. Then, a comprehensive analysis of network capability was performed with the curated model and compared with the published metabolic reconstruction. The flux distribution obtained by lipid optimization with flux balance analysis was able to replicate the internal biochemical changes that lead to lipogenesis in oleaginous microorganisms. These results motivate the development of a genome-scale model for complete elucidation of R. toruloides metabolism. PMID- 29787799 TI - New insights on the phylogenetic relationships among the traditional Philodendron subgenera and the other groups of the Homalomena clade (Araceae). AB - Philodendron (Araceae) is one of the largest Neotropical plant genera, with approximately 500 species and at least 1000 species predicted. There is a considerable ecological diversity in the group, although most species occur in the humid forests of tropical America. Despite being relatively well-studied in taxonomic analyses, the relationships among the traditional morphological groups of the genus are not well-established, mainly regarding the three traditional subgenera, referred here as Philodendron sensu lato (s.l.), P. subg. Pteromischum, P. subg. Philodendron and P. subg. Meconostigma, which was recently recognized as a separate genus, Thaumatophyllum. Therefore, the present work evaluates the phylogenetic position and the monophyly of Philodendron s.l. and its three main subdivisions, and the sister groups within the Homalomena clade, which also includes the Neotropical genus Adelonema, the two Asian genera Homalomena and Furtadoa, and the two African genera Cercestis and Culcasia, by means of molecular phylogenetic approaches including chloroplast DNA (atpF-atpH, rpl32-trnL, trnQ-5'-rps16 and trnV-ndhC) and nuclear (ITS2) markers. The monophyly of Philodendron s.l. and its three lineages is confirmed and our analyses corroborate previous morphologic data indicating Thaumatophyllum as sister to the clade formed by P. subg. Pteromischum and P. subg. Philodendron. PMID- 29787800 TI - The effect of formulation on spray dried Sabin inactivated polio vaccine. AB - The objective of this study was to develop a stable spray dried formulation, containing the three serotypes of Sabin inactivated polio vaccine (sIPV), aiming for minimal loss of native conformation (D-antigen) during drying and subsequent storage. The influence of atomization and drying stress during spray drying on trivalent sIPV was investigated. This was followed by excipient screening, in which monovalent sIPV was formulated and spray dried. Excipient combinations and concentrations were tailored to maximize both the antigen recovery of respective sIPV serotypes after spray drying and storage (T = 40 degrees C and t = 7 days). Furthermore, a fractional factorial design was developed around the most promising formulations to elucidate the contribution of each excipient in stabilizing D-antigen during drying. Serotype 1 and 2 could be dried with 98% and 97% recovery, respectively. When subsequently stored at 40 degrees C for 7 days, the D-antigenicity of serotype 1 was fully retained. For serotype 2 the D antigenicity dropped to 71%. Serotype 3 was more challenging to stabilize and a recovery of 56% was attained after drying, followed by a further loss of 37% after storage at 40 degrees C for 7 days. Further studies using a design of experiments approach demonstrated that trehalose/monosodium glutamate and maltodextrin/arginine combinations were crucial for stabilizing serotype 1 and 2, respectively. For sIPV serotype 3, the best formulation contained Medium199, glutathione and maltodextrin. For the trivalent vaccine it is therefore probably necessary to spray dry the different serotypes separately and mix the dry powders afterwards to obtain the trivalent vaccine. PMID- 29787802 TI - Permeability and diffusivity of nitric oxide in human plasma and red cells. AB - A simple diffusion cell was made to measure the permeability and diffusivity of Nitric Oxide in human plasma and red cells. Nitric oxide was passed through the cell containing plasma or nitrited red cells enclosed by silicone membranes. Steady state permeability (alphaNODNO ) was calculated from the cell dimensions and from the NO bulk flow entering and leaving the cell. The diffusion coefficient (DNO) was calculated in three ways: (i) by dividing the steady state permeability by published values for solubility (alphaNO ) in water at 26 degrees C and 37 degrees C (ii) by a numerical method and (iii) by an analytical method. Mean steady state permeability (95% confidence intervals) were plasma (26 degrees C) 5.57 * 10-11 (2.35 * 10-11-1.32 * 10-10) and (37 degrees C) 5.48 * 10-11 (2.13 * 10-11-1.41 * 10-10) mol cm-1 s-1 atm-1 and red cells (26 degrees C) 6.74 * 10-12 (1.29 * 10-12-3.53 * 10-11) and (37 degrees C) 3.93 * 10-11 (1.39 * 10-11-1.11.10-10) mol cm-1 s-1 atm-1. Median Diffusion Coefficients (DNO) for plasma at 37 degrees C ranged from 3-3.36 * 10-5 cm2 s-1 and red cells 2.41 2.94 * 10-5 cm2 s-1 depending on the method used. These values may be used for modelling NO transport in vivo in the human lung and capillary. Parameters used for modelling in vivo should be measured at 37 degrees C. PMID- 29787801 TI - Looking inside the 'black box': Freezing engineering to ensure the quality of freeze-dried biopharmaceuticals. AB - The freezing step plays a central role in reaching the most stringent requirements of quality, homogeneity and standardization of freeze-dried products. In this paper, a systematic procedure has been proposed to obtain a quantitative estimation of the pore-size variability of lyophilized products resulting from uncontrollable variations of the nucleation temperature. This procedure consisted in collecting the nucleation temperature from a statistically significant number of samples and correlating each nucleation temperature to the corresponding product morphology, using a mathematical model, to obtain a statistical description of the lyophilized product structure. This approach can also be used to obtain an estimation of the variability of the mass transfer resistance to vapor flow and, finally, of the drying time. Two different freezing configurations, i.e., conventional and suspended-vial freezing, have been used as case studies since they can produce significantly different freezing rates. PMID- 29787804 TI - The prognostic significance of preoperative neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma receiving hepatectomy: A systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Numerous reports have indicated that preoperative Neutrophil Lymphocyte ratio (NLR) was correlated with the prognosis of hepatocellular carcinoma who underwent hepatectomy. However, the results still remained controversial. Therefore, the present meta-analysis of 17 studies was performed to evaluate the prognostic value of preoperative NLR in HCC patients. METHOD: Databases of PubMed, Embase, Cochrane Library and Web of Science were retrieved. Hazard Ratio (HR) or Odds Ratio (OR) with its 95% confidence intervals (CI) was used to evaluate the association between preoperative NLR and the prognosis or clinical features of HCC patients. RESULT: A total of 17 studies eventually were included in this meta-analysis. Elevated preoperative NLR had a close relationship with the overall survival (OS) (HR 1.52; 95% CI 1.37-1.69), recurrence-free survival (RFS) (HR 1.64; 95% CI 1.44-1.87) and disease-free survival (DFS) (HR 1.50; 95% CI 1.35-1.67) of hepatocellular carcinoma. Additionally, preoperative NLR was also associated with tumor vascular invasion (OR 2.08; 95% CI 1.60-2.70), HBV (OR 0.68; 95% CI 0.51-0.90) and large tumor size (OR: 4.07; 95% CI 2.60-6.37). CONCLUSION: The present meta-analysis indicated that preoperative NLR had significant association with the prognosis of hepatocellular carcinoma patients and may be an effectively prognostic indicator. PMID- 29787803 TI - Quality of life and functional assessment of facial palsy patients: A questionnaire study. AB - BACKGROUND: Facial palsy leads to functional and aesthetic deficits, which impair the quality of life of affected patients. General health-related and disease specific questionnaires are available for quality of life assessment. In this study, observer-based analysis of facial function (Sunnybrook Facial Grading Scale) was compared patient-based to facial palsy-specific gradings (Facial Clinimetric Evaluation Scale and Facial Disability Index), and general health related quality of life questionnaires (SF-36). We hypothesized that only facial palsy-specific instruments capture functional and social impairments of affected patients. METHODS: Thirty facial palsy patients treated at a tertiary referral centre were included in this study. Inclusion criteria were unilateral facial palsy with stable facial function, age over 18 years and fluency in German. Facial function was assessed with general and disease-specific patient-reported outcome measures and subsequently evaluated by the treating facial plastic surgeon. Statistical analysis included descriptive statistics for all assessed measurements. Correlations were calculated to compare general and facial palsy specific instruments, as well as observer-based grading. RESULTS: Observer-based evaluation of facial function correlated well to the patients-based assessment of physical function, however social subscores did not correlate demonstrating the limited correlation of patient distress and facial nerve impairment. Physical function scores of disease-specific instruments did not correlate with general health assessment scores, while social function scores showed moderate to good correlations. CONCLUSION: Validated disease-specific instruments are essential for the assessment of facial palsy patients. Patient-reported outcome measures like the FaCE Scale and the Facial Disability Index should be applied in addition to standardized observer-based ratings to capture the patients' perspective on functional and social impairments associated with facial palsy to fully assess the burden of disease. PMID- 29787805 TI - N-acylanthranilic acid derivatives with anti-Abeta1-42 aggregation activity from the leaves of Isatis indigotica fortune. AB - Seven new N-acylanthranilic acid derivatives (1-3, 4a/4b, 5a/5b) including two pairs of enantiomers (4a/4b and 5a/5b) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-Abeta1-42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect Abeta1-42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b. PMID- 29787806 TI - Factors associated with post-election psychological distress: The case of the 2016 U.S. presidential election. AB - This study, through the lens of Social Cognitive Theory, examined potential risk factors that may intensify election-related psychological distress. Six weeks after the 2016 U.S. election, 772 U.S. adult citizens filled out an online survey that assessed psychological distress along with sociodemographic characteristics, and a set of variables tapping various dimensions of political self-efficacy (i.e., importance of politics in one's life, preferences for different media outlets, political directness, and voting choices). The findings showed that election-related psychological distress was positively associated with young age, greater reliance on new media, greater importance of politics in one's life, higher political directness, and voting for the candidate who did not win the election. Findings should be valuable for health-care providers informing them about potential risk factors intensifying psychological distress in the context of significant political events. PMID- 29787807 TI - Temperament and characteristics related to nomophobia. AB - Nomophobia is defined as the fear of being out of mobile phone contact and is considered to be a phobia of the modern age. The current study set out to establish the relationship between temperament and personality and the development of nomophobia. The sample was composed of 968 participants selected from the Andalusian population, of which there were 182 males and 785 females aged from 23.19 years. The instruments used were the Questionnaire to Assess Nomophobia (QANIP; Olivencia-Carrion et al., 2018) and the Temperament and Character Inventory Revised (TCI-R; Cloninger et al., 1993). We found that cooperation is a characteristic that significantly reduces nomophobic levels, particularly for the two factors of Mobile Phone Addiction and Negative Consequences. Furthermore, Reward Dependence appears to be positively related to two of the factors involved in nomophobia, namely Mobile Phone Addiction and Loss of Control, suggesting a relationship between Nomophobia and personality. These findings are discussed in terms of their usefulness for identifying the personality predictors of nomophobia in order to develop preventive and intervention strategies. PMID- 29787808 TI - Lipoxin A4 and its analog suppress hepatocarcinoma cell epithelial-mesenchymal transition, migration and metastasis via regulating integrin-linked kinase axis. AB - Epithelial-mesenchymal Transition (EMT) and migration play an important role in tumor progression, and lipoxin (LX), the 'stop signal' for inflammation, has been studied in basic research for its anti-inflammatory or inflammatory pro-resolving properties. Here, in the in vitro experiment, we showed that LXA4 could inhibit the EMT and migration in phorbol myristate acetate (PMA) or activated conditioned medium (ACM)-stimulated Hep3B cells by downregulation of integrin-linked kinase (ILK), a pseudokinase in cytoplasm and these effects were via inhibiting the phosphorylation of Akt and GSK3beta. Morover, LXA4 could not affect the EMT and migration of PMA-stimulated Hep3B cells by knockdown of ILK. In the in vivo experiment, BML-111 (the analog of LXA4) could inhibit the EMT and metastasis of hepatocarcinoma cells. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3beta, decreased expression of MMP-2 and MMP-9. These results showed that LXA4 could be a possible candidate for liver cancer therapy, and blocking ILK axis would be an effective drug target. PMID- 29787810 TI - Comparison of several biomarkers (MMP-2, MMP-9, the MMP-9 inhibitor TIMP-1, CTX II, calprotectin, and COMP) in the synovial fluid and serum of patients with and without septic arthritis. PMID- 29787811 TI - Gout furonculosis. PMID- 29787812 TI - Muscular sarcoidosis under anti-TNF treatment in ankylosing spondylitis. PMID- 29787809 TI - EET enhances renal function in obese mice resulting in restoration of HO-1-Mfn1/2 signaling, and decrease in hypertension through inhibition of sodium chloride co transporter. AB - BACKGROUND: We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity induced renal dysfunction by improving sodium excretion, reducing the sodium chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1alpha dependent mice. METHODS: EET-agonist treatment normalized glucose metabolism, renal ENaC and NCC protein expression, urinary sodium excretion and blood pressure in obese (db/db) mice. A marked improvement in mitochondrial integrity, thermogenic genes, and PGC-1alpha-HO-1 adiponectin signaling occurred. Knockout of PGC-1alpha in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in sodium excretion, elevation of blood pressure and an increase in the pro-inflammatory adipokine nephroblastoma overexpressed gene (NOV). In the elucidation of the effects of EET on peri-renal adipose tissue, EET increased adiponectin, mitochondrial integrity, thermogenic genes and decreased NOV, i.e. "Browning' peri-renal adipose phenotype that occurs under high fat diets. Taken together, these data demonstrate a critical role of an EET agonist in the restoration of healthy adipose tissue with reduced release of inflammatory molecules, such as AngII and NOV, thereby preventing their detrimental impact on sodium absorption and NCC levels and the development of obesity-induced renal dysfunction. PMID- 29787813 TI - Vascular involvement in axial spondyloarthropathies. AB - Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that involves the entheses, causing inflammatory pain and functional impairments. Patients may experience extraarticular manifestations such as uveitis, psoriasis, and inflammatory bowel disease. These, together with the increased risk of cardiovascular disease and osteoporosis and the development of spinal fusion, are the main determinants of adverse disease outcomes. As with many systemic inflammatory diseases, AS is associated with excess cardiovascular mortality due to increased risks of myocardial infarction, stroke, and venous thromboembolism. Studies of markers for subclinical atheroma (endothelial dysfunction, arterial stiffness, and intima-media thickness) have shown earlier onset of arterial disease compared to healthy controls, with the difference being greatest for patients with active AS. The potential vascular effects of drugs used to treat AS have not been established. Few studies have focused on nonsteroidal antiinflammatory drugs and biologics in patients with AS, and their results do not conclusively establish a beneficial or deleterious effect in axial spondyloarthritis. Statins have been found to improve endothelial dysfunction and to decrease mortality. The latest EULAR recommendations on cardiovascular risk management in patients with inflammatory joint disease indicate that statins should be used in compliance with national guidelines. PMID- 29787814 TI - Lipid-modified cell-penetrating peptide-based self-assembly micelles for co delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy. AB - : Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and one therapeutic approach is to target both the AMPK and autophagy pathways in order to synergistically promote programmed cell death. Here, a series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and allowed to self-assemble into micelles loaded with the AMPK activator narciclasine (Narc) and short interfering RNA targeting the unc-51-like kinase 1 (siULK1). The size of these micelles, their efficiency of transfection into cells, and their ability to release drug or siRNA cargo in vitro were pH sensitive, such that drug release was facilitated in the acidic microenvironment of the tumor. Transfecting the micelles into HCC cells significantly inhibited protective autophagy within tumor cells, and delivering the micelles into mice carrying HCC xenografts induced apoptosis, slowed tumor growth, and inhibited autophagy. Our results indicate that co-delivering Narc and siULK1 in biocompatible micelles can safely inhibit tumor growth and protective autophagy, justifying further studies into this promising therapeutic approach against HCC. STATEMENT OF SIGNIFICANCE: We have focused on the targeted therapy of HCC via synergistically inhibiting the autophagy and inducing apoptosis. The lipid modified cell-penetrating peptide can not only aggregate into micelles to load natural product narciclasine and ULK1 siRNA simultaneously, but also facilitate uptake and endosome escape with a pH-sensitive manner in HepG2 cells. HepG2 cell treated with siULK1-M-Narc has increased apoptotic levels and declined autophagy via the targeted regulation of AMPK-ULK1 signaling axis. The in vivo studies have confirmed that siULK1-M-Narc efficiently reduce the growth of tumor on HCC xenograft models with good safety. Thus, we suppose the lipid-modified cell penetrating peptide has good application prospects in the targeted combinational therapy of HCC. PMID- 29787815 TI - Two extracellular sialidases from Bifidobacterium bifidum promote the degradation of sialyl-oligosaccharides and support the growth of Bifidobacterium breve. AB - We investigated the roles of extracellular sialidases (SiaBb1 and SiaBb2) in cross-feeding between sialidase-carrying Bifidobacterium bifidum and sialic acid utilizing Bifidobacterium breve. Using 6' sialyllactose (6'SL) as a carbon source, the number of wild-type B. bifidum cells increased while that of a siabb2 inactivated strain (Deltasiabb2) did not. Coculture of these two strains in the presence of 6'SL resulted in similar increase in cell numbers. Coculture of wild type B. bifidum, but not the Deltasiabb2 strain, with sialic acid-utilizing Bifidobacterium breve, which cannot release sialic acids from carbohydrates, in the presence of 6'SL increased the number of B. breve cells. Moreover, when mucin was used as a carbon source, B. breve growth was increased in cocultures with B. bifidum wild-type and Deltasiabb2 strains, suggesting that SiaBb1 may be involved. Additionally, B. breve cell numbers increased during cultivation with recombinant SiaBb1-and SiaBb2-treated mucin as the sole carbon source. These results indicated that B. bifidum SiaBb2 liberated sialic acid from sialyl-human milk oligosaccharides and -mucin glycans, supporting the growth of B. breve through sialic acid cross-feeding. SiaBb1 may assist in the degradation of mucin glycan. Collectively, our results revealed that both the B. bifidum extracellular sialidases promote the utilization of sialylated carbohydrates and supply free sialic acid to other Bifidobacterium strains. PMID- 29787816 TI - O-GlcNAcylation and neuronal energy status: Implications for Alzheimer's disease. AB - Since the first clinical case reported more than 100 years ago, it has been a long and winding road to demystify the initial pathological events underling the onset of Alzheimer's disease (AD). Fortunately, advanced imaging techniques extended the knowledge regarding AD origin, being well accepted that a decline in brain glucose metabolism occurs during the prodromal phases of AD and is aggravated with the progression of the disease. In this sense, in the last decades, the post-translational modification O-linked beta-N acetylglucosaminylation (O-GlcNAcylation) has emerged as a potential causative link between hampered brain glucose metabolism and AD pathology. This is not surprising taking into account that this dynamic post-translational modification acts as a metabolic sensor that links glucose metabolism to normal neuronal functioning. Within this scenario, the present review aims to summarize the current understanding on the role of O-GlcNAcylation in neuronal physiology and AD pathology, emphasizing the close association of this post-translational modification with the emergence of AD-related hallmarks and its potential as a therapeutic target. PMID- 29787817 TI - Analysis of hepatitis B virus infection in blood sera using Raman spectroscopy and machine learning. AB - This study presents the analysis of hepatitis B virus (HBV) infection in human blood serum using Raman spectroscopy combined with pattern recognition technique. In total, 119 confirmed samples of HBV infected sera, collected from Pakistan Atomic Energy Commission (PAEC) general hospital have been used for the current analysis. The differences between normal and HBV infected samples have been evaluated using support vector machine (SVM) algorithm. SVM model with two different kernels i.e. polynomial function and Gaussian radial basis function (RBF) have been investigated for the classification of normal blood sera from HBV infected sera based on Raman spectral features. Furthermore, the performance of the model with each kernel function has also been analyzed with two different implementations of optimization problem i.e. Quadratic programming and least square. 5-fold cross validation method has been used for the evaluation of the model. In the current study, best classification performance has been achieved for polynomial kernel of order-2. A diagnostic accuracy of about 98% with the precision of 97%, sensitivity of 100% and specificity of 95% has been achieved under these conditions. PMID- 29787818 TI - Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma. AB - The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index, apoptotic index, and microvessel density were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multivariate analyses (hazard ratio = 1.41, 95% confidence interval = 1.03-1.93, P = .031) and was significantly correlated with proliferation index, apoptotic index, and microvessel density (r = .47, P <. 001; r = -.31, P < .001; and r = .40, P < .001, respectively). In conclusion, CD57+ cells, CD68+ cells, and mast cells played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. PMID- 29787819 TI - Budding and tumor-infiltrating lymphocytes - combination of both parameters predicts survival in colorectal cancer and leads to new prognostic subgroups. AB - Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well defined by the International Concensus Conference on Tumor Budding (ITBCC). Tumor-infiltrating lymphocytes (TILs) are also an issue in different human cancers and correlate with prognosis in CRC. Here we evaluate the combination of budding and TILs in CRC with regard to prognosis. Hematoxylin and eosin (H&E)-stained slides of 501 CRC patients, diagnosed between 2005 and 2010, were reevaluated for tumor budding according to the ITBCC criteria. Low (n = 331) was compared to intermediate/high budding (n = 170). The percentage of TILs was also assessed, and the following four groups were established: low budding + TILs >5% (n = 162), low budding + TILS <=5% (n = 169), high budding + TILS >5% (n = 68), high budding + TILs <=5% (n = 93). The combination of both markers revealed highly significant differences in overall survival (OS) between the four groups (P = .001). The low budding/>5% TILs group showed longest OS, followed by high budding/>5% TILs cases, followed by tumors with low budding/<=5% TILs. OS was worst for the high budding/<= 5% TILs group. The combined score also correlated with T, N, M, L, Vstaging, development of disease relapse and distant metastasis. Our study shows that - even in the age of molecular pathology - it is still important to pay special attention to tumor morphology for additional information on tumor behavior and prognosis. Combining different morphological parameters of tumor and tumor environment can help to further subdivide CRC into new prognostic groups. PMID- 29787820 TI - Clinicopathological characteristics of thyroid transcription factor 1-negative small cell lung cancers. AB - Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer; however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (ASCL1, BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (NF1B). Formalin-fixed and paraffin-embedded sections of SCLC tumors were subjected to immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analyses. In a case-control cohort matched for basic clinical factors, expression of ProGRP, synaptophysin, chromogranin A, and ASCL1 was significantly decreased in TTF-1-negative SCLC samples. In contrast, there was no significant correlation between Ki-67 labeling index and TTF-1. In a larger serial case cohort, TTF-1-negative SCLC cases were older at diagnosis, but there was no significant difference in the overall survival of patients with TTF 1-negative and TTF-1-positive SCLC. In conclusion, TTF-1-negative SCLC showed decreased neuroendocrine differentiation, and significantly worse clinical outcomes were not observed. PMID- 29787821 TI - SLC25A13 c.1610_1612delinsAT mutation in an Indian patient and literature review of 79 cases of citrin deficiency for genotype-phenotype associations. AB - Here, we report SLC25A13 c.1610_1612delinsAT mutation from India in a 13-year old boy who presented with recurrent episodes of delirium and hyperammonemia. This is the second case with this mutation; the first case was of Pakistani origin. The boy responded to diet modification, sodium benzoate and arginine supplementation. Furthermore, we have aimed to establish genotype-phenotype correlation of 79 cases of citrin deficiency (46 males and 33 females) reported in 24 studies from all over the world. Inverse association was observed between age of onset and jaundice (r = -0.73). Late age of onset was associated with delirium (r = 0.61), aggressive behaviour (r = 0.67), altered sensorium (r = 0.67) and tremors (r = 0.65). The most common mutations associated with citrin deficiency were c.851_854del4, IVS16ins3kb, 1638-1660dup with a frequency of 42.41%, 16.46% and 6.33%, respectively. The c.851_854del4 mutation showed positive association with alpha feto protein (r = 0.40), ammonia (r = 0.50) and tyrosine (r = 0.40) while showing inverse association with threonine (r = -0.55). The IVS16ins3kb mutation was associated with high total (r = 0.65) and conjugated bilirubin (r = 0.54) along with high aspartate transaminase (r = 0.49) while citrulline levels are lower (r = -0.36). To conclude, all cases of intrahepatic cholestasis and neuropsychiatric abnormalities should be evaluated for citrin deficiency. However, the ethnic group-specific mutation frequencies should be considered in implementing screening. PMID- 29787823 TI - Members of the neuropeptide transcriptional network in Helicoverpa armigera and their expression in response to light stress. AB - Neuropeptides and peptide hormones play central roles in the regulation of various types of insect physiology and behavior. Artificial light at night, a form of environmental stress, has recently been regarded as a source of light stress on nocturnal insects. Because related genomic information is not available, molecular biological studies on the response of neuropeptides in nocturnal insects to light stress are limited. Based on the de novo sequencing of the Helicoverpa armigera head transcriptome, we obtained 124,960 unigenes. Of these, the number of unigenes annotated as neuropeptides and peptide hormones, neurotransmitter precursor processing enzymes, and neurotransmitter receptors were 34, 17, and 58, respectively. Under light stress, there were sex-specific differences in gene expression measured by qRT-PCR. The IMFamide, leucokinin and sNPF genes were differentially expressed at the mRNA level in males but not in females in response to light stress. The results provide new insights on the diversity of the neuropeptide transcriptional network of H. armigera. In addition, some neuropeptides exhibited sex-specific differential expression in response to light stress. Taken collectively, these results not only expand the catalog of known insect neuropeptides but also provide a framework for future functional studies on the physiological roles they play in the light stress response behavior of nocturnal moths. PMID- 29787822 TI - The complete plastome sequence of Rubus takesimensis endemic to Ulleung Island, Korea: Insights into molecular evolution of anagenetically derived species in Rubus (Rosaceae). AB - Previous phylogenetic studies have suggested that Rubus takesimensis (Rosaceae), which is endemic to Ulleung Island, Korea, is closely related to R. crataegifolius, which is broadly distributed across East Asia. A recent phylogeographic study also suggested the possible polyphyletic origins of R. takesimensis from multiple source populations of its continental progenitor R. crataegifolius in China, Japan, Korea, and the Russian Far East. However, even though the progenitor-derivative relationship between R. crataegifolius and R. takesimensis has been established, little is known about the chloroplast genome (i.e., plastome) evolution of anagenetically derived species on oceanic islands and their continental progenitor species. In the present study, we characterized the complete plastome of R. takesimensis and compared it to those of R. crataegifolius and four other Rubus species. The R. takesimensis plastome was 155,760 base pairs (bp) long, a total of 46 bp longer than the plastome of R. crataegifolius (28 from LSC and 18 from SSC). No structural or content rearrangements were found between the species pairs. Four highly variable intergenic regions (rpl32/trnL, rps4/trnT, trnT/trnL, and psbZ/trnG) were identified between R. takesimensis and R. crataegifolius. Compared to the plastomes of other congeneric species (R. corchorifolius, R. fockeanus, and R. niveus), six highly variable intergenic regions (ndhC/psaC, rps16/trnQ, trnK/rps16, trnL/trnF, trnM/atpE, and trnQ/psbK) were also identified. A total of 116 simple sequence repeats (SSRs), including 48 mononucleotide, 64 dinucleotide, and four trinucleotide repeat motifs were characterized in R. takesimensis. The plastome resources generated by the present study will help to elucidate plastome evolution within the genus and to resolve phylogenetic relationships within highly complex and reticulated lineages. Phylogenetic analysis supported both the monophyly of Rubus and the sister relationship between R. crataegifolius and R. takesimensis. PMID- 29787824 TI - Discovery and expression analysis of novel transcripts of the human SR-related CTD-associated factor 1 (SCAF1) gene in human cancer cells using Next-Generation Sequencing. AB - The human SR-related CTD associated factor 1 (SCAF1) gene is a new member of the human SR (Ser/Arg-rich) superfamily of pre-mRNA splicing factors, which has been discovered and cloned by members of our lab. SCAF1 interacts with the CTD domain of the RNA polymerase II polypeptide A and is firmly involved in pre-mRNA splicing. Although it was found to be expressed widely in multiple human tissues, its mRNA levels vary a lot. The significant relation of SCAF1 with cancer has been confirmed by many studies, since SCAF1 mRNA transcript was found to be overexpressed in breast and ovarian tumors, confirming its significant prognostic value as a cancer biomarker in both these human malignancies. In this study, we describe the discovery and cloning of fifteen novel transcripts of the human SCAF1 gene (SCAF1 v.2 - v.16), using nested PCR and NGS technology. In detail, extensive bioinformatic analysis revealed that these novel SCAF1 splice variants comprise a total of nine novel alternative splicing events between the annotated exons of the gene, thus producing seven novel SCAF1 transcripts with open-reading frames, which are predicted to encode novel SCAF1 isoforms and eight novel SCAF1 transcripts with premature termination codons that are likely long non-coding RNAs. Additionally, a novel 3' UTR was discovered and cloned using nested 3' RACE and was validated with Sanger sequencing. In order to validate the NGS findings as well as to investigate the expression profile of each novel transcript, RT-PCR experiments were carried out with the use of variant-specific primers. Since SCAF1 is implicated in many human malignancies, qualifying as a potential biomarker, the quantification of the presented novel transcripts in human samples may have clinical applications in different types of cancer. PMID- 29787825 TI - Congenital sideroblastic anemia: Advances in gene mutations and pathophysiology. AB - Congenital sideroblastic anemia (CSA) is a series of rare, heterogeneous disorders, characterized by iron overload in the mitochondria of erythroblasts and ringed sideroblasts in bone marrow. In recent years, rapid development of next-generation sequencing technology brings great advance in understanding of genetic and pathophysiologic features of CSA. Based on the pathophysiology of mitochondrial iron metabolism, causative genes of CSA can be divided into three subtypes: heme biosynthesis related; iron-sulfur cluster biosynthesis and transportation related; and mitochondrial respiratory chain synthesis related. Patients with CSA present various clinical manifestation due to relevant mutation gene and require different treatment strategies. The recognition of the causative genes and evolution of pathogenicity is critical. In this review, we summarize the recent progress in mutation genes of CSA, and its potential role in the pathogenesis, diagnosis and treatment. PMID- 29787826 TI - Obesity-induced overexpression of miRNA-24 regulates cholesterol uptake and lipid metabolism by targeting SR-B1. AB - Scavenger Receptor B1 (SR-B1) is an 82 kDa integral membrane glycoprotein that mediates selective uptake of high-density lipoprotein cholesteryl ester (CE) in vitro and in vivo. Previously, we defined several kinds of regulatory mechanisms of SR-B1 expression and function. Here, we have dissected the function of a novel miR-24 on SR-B1 expression, HDL uptake and lipid metabolism. We showed that miR 24 was upregulated in HepG2 cells cultured in the mimicked hyperlipidemic condition and in the livers of dietary induced and genetic obesity mice. Overexpression of miR-24 inhibited SR-B1 expression by directly targeting SR-B1 3' UTR and repressed HDL uptake and steroidogenesis in steroidogenic cells. HepG2 cells with miR-24 showed attenuation of TG levels and lipid accumulation. Moreover, we validated that overexpression of miR-24 downregulated the expression of certain genes involved in lipogenesis, FASN, ACLY and SCD1, and increased the expression of genes of cholesterol synthesis, HMGCR, DHCR24 and SREBP2. Taken together, we demonstrated that obesity induced miR-24 repressed HDL uptake, steroid hormone synthesis and lipid metabolism by targeting SR-B1. PMID- 29787827 TI - Genetic variants of fatty acid elongase 6 in Chinese Holstein cow. AB - In the dairy industry, genetic variants have contributed to the improvement of milk production traits. Fatty acid elongase 6 (ELOVL6), which elongates saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), plays a distinct role in the balance of long-chain fatty acids composition in animals. ELOVL6 catalyzes the elongation of palmitic acids (C16:0) which is the most common saturated fatty acid found in animals and also an essential precursor to synthesize other long chain fatty acids. However, the genetic variant research of bovine ELOVL6 on milk quality traits is still unknown. Therefore, our study aimed to detect the single nucleotide polymorphism (SNPs) of bovine ELOVL6 and explored the relationship between SNPs and milk quality traits including milk yield, fat content, protein content and somatic cell score. In this study, three SNPs, including SNP1 (g16379651A>G), SNP2 (g16458976A>G) and SNP3 (g16511290A>G), have been identified in intron 3 and 3'UTR regions of ELOVL6 in Chinese Holstein (CH) cows. Besides, the results of genetic diversity analysis, linkage disequilibrium and haplotype analysis indicated that these SNPs presented moderate polymorphisms which reflected relatively high genetic diversity. No strong linkage among these SNPs were detected in sampled population of cows. Moreover, the results of correlation analyses demonstrated that these SNPs of bovine ELOVL6 were significantly related to milk yield (P < 0.05). The SNP1 was also correlated with somatic cell score, whereas the SNP3 was associated with fat content. The 21 combined genotypes (diplotypes) were highly significantly correlated (P < 0.01) with milk yield. These results revealed that the genetic variants of bovine ELOVL6 influenced the milk production of CH cows. Hence, the three SNPs could be regarded as molecular markers in marker-assisted selection (MAS) of the dairy cow breeding. PMID- 29787828 TI - Negative associations of frozen compared with fresh vegetables. AB - Despite convenience and nutrition advantages of frozen vegetables, consumption of them is low compared with fresh vegetables and continues to decrease. In two studies, we observe a negative bias for frozen vegetables compared with fresh vegetables. In study 1, we used an Implicit Association Test (IAT) to demonstrate that generalized negative associations with frozen vegetables are automatic, robust, and ingrained in long-term memory. In study 2, we conceptually replicate this finding with an explicit measure and extend it by examining the role of transforming the food product in formation of the observed negative bias. We find no improvement in evaluation for frozen spinach when participants contemplate the final cooked product. Instead, we see less favorable evaluations of fresh spinach when participants contemplate the final cooked product. These findings are consistent with previous research that demonstrates that transformation of a food from its "natural" state leads to less favorable evaluations of it. PMID- 29787829 TI - Social reward and social punishment sensitivity in relation to dietary restraint and binge/purge symptoms. AB - Disordered eating symptoms are associated with disrupted sensitivity to reward and punishment, broadly assessed. However, it is unknown how eating pathology is related to sensitivity to social reward and social punishment specifically. Drawing on Reinforcement Sensitivity Theory, the current study utilized a multi method design to test whether disordered eating symptoms, specifically dietary restraint (DR) and binge/purge (BP), were similarly or uniquely related to sensitivity to social punishment and social reward. Female university students (N = 110, M = 18.66, SD = 0.89) completed self-report measures and a novel behavioral task measuring willingness to work for or to avoid social feedback. DR and BP symptoms were related to increased self-reported and behavioral sensitivity to social punishment, yet only when symptoms were tested in isolation. DR was associated with increased sensitivity to social reward across self-report and behavioral paradigms. BP symptoms were uniquely and positively related to self-reported sensitivity to social reward, but decreased behavioral sensitivity to social reward. Findings suggest that sensitivity to punishment may be a common factor related to DR and BP, whereas sensitivity to social reward may be a key factor differentiating disordered eating symptoms. PMID- 29787830 TI - The utility of event-related potentials (ERPs) in understanding food-related cognition: A systematic review and recommendations. AB - Daily dietary decisions have the potential to impact our physical, mental, and emotional health. Event-related potentials (ERPs) can provide insight into cognitive processes, such as attention, working memory, and inhibitory control, that may influence the food-related decisions we make on a daily basis. We conducted a systematic review of the food-related cognition and ERP research in order to summarize the extant literature, identify future research questions, synthesize how food-related ERP components relate to eating habits and appetite, and demonstrate the utility of ERPs in examining food-related cognition. Forty three articles were systematically extracted. In general, results indicated food cues compared to less palatable foods or neutral cues elicited greater ERP amplitudes reflecting early or late attention allocation (e.g., increased P2, P3, late positive potential amplitudes). Food cues were associated with increased frontocentral P3 and N2 ERP amplitudes compared to neutral or less palatable food cues, suggesting increased recruitment of inhibitory control and conflict monitoring resources. However, there was significant heterogeneity in the literature, as experimental tasks, stimuli, and examined ERP components varied widely across studies, and therefore replication studies are needed. In-depth research is also needed to establish how food-related ERPs differ by BMI groups and relate to real-world eating habits and appetite, in order to establish the ecological validity. PMID- 29787831 TI - Oleoylethanolamide increases the expression of PPAR-Alpha and reduces appetite and body weight in obese people: A clinical trial. AB - Obesity is a crucial public health problem worldwide and is considered as the main cause of many chronic diseases. The present study evaluated the effects of Oleoylethanolamide (OEA) supplementation on proximal proliferator-activated receptor-alpha (PPAR-alpha) gene expression, appetite sensations, and anthropometric measurements in obese people. This randomized, double-blind, placebo-controlled clinical trial was carried out on 60 healthy obese people in Tabriz, Iran, in 2016. The eligible subjects were divided into an intervention group (who received two 125 mg OEA capsules daily) and a placebo group (who received the same amount of starches) and treated for 60 days. Anthropometric measurements and body composition were assessed in a fasting state at baseline and at the end of the study. The visual analogue scales (VAS) were used to assess appetite sensations. Quantitative real-time PCR analysis targeting the 16S rRNA gene of PPAR-alpha was done. Analysis was done on 56 participants who continued intervention until the end of the study. A significant increase in PPAR-alpha gene expression was observed in the intervention group (p < 0.001). Weight, body mass index, waist circumference, and fat percent decreased significantly at the end of the study in the intervention group (all p < 0.01). Hunger, the desire to eat, and cravings for sweet foods decreased significantly and fullness increased significantly by the end of study in the intervention group at the end of study (all p < 0.01). The fullness item increased significantly by the end of study in the intervention group (p < 0.001). Use of OEA as a complementary approach could be effective in suppressing appetite and modulating energy balance in obese people. PMID- 29787832 TI - A comparative study of quality of life, functional and bone outcomes in osteogenesis imperfecta with bisphosphonate therapy initiated in childhood or adulthood. AB - Bisphosphonates have been used for treatment of bone fragility disorders for over 25 years to increase bone mineral density (BMD). Anecdotally, bisphosphonate treated Osteogenesis Imperfecta (OI) has a different trajectory to the natural history of untreated OI in terms of fracture incidence, quality of life and physical function, with minimal published evidence to support this clinical observation. This study describes functional outcomes of a cohort of adults with OI, stratified according to severity and treated with intravenous bisphosphonates as children. Reported outcomes included fracture incidence before and after puberty, mobility and BMD outcomes of this cohort. The cohort was compared to adults with OI who were never treated as children. All participants completed four questionnaires: a study specific questionnaire addressing fracture and treatment history, WHOQOL-BREF (quality of life), SF-36 (musculoskeletal function) and IPAQ (physical activity), and medical records were reviewed. Fifty two adults with OI (80% response rate) completed the questionnaires; 33 of whom were treated with bisphosphonates in childhood. The childhood treated cohort had higher lumbar spine BMD than the adult treated cohort (z-score - 0.4 at mean age 21.3 years versus -2.1 at mean age 40.9 years; p = 0.003). Pre-pubertal fracture incidence was reduced for all severities of OI in the childhood treated cohort (less severe OI, p = 0.01; more severe OI, p < 0.001), but post-pubertal fracture incidence was higher for less severe OI (p < 0.001). In less severe OI, childhood treated individuals had higher levels of physical activity (p = 0.004) and physical functioning (p = 0.01) than adult treated individuals. Incidence of scoliosis was not different between cohorts. There were no differences in quality of life scores between the two cohorts. Improvements in BMD do not appear to influence the prevalence of scoliosis. Results suggest that treatment with bisphosphonates at an earlier age improves physical activity, particularly in less severe forms of OI but may not alter quality of life. PMID- 29787833 TI - Dehydroepiandrosterone: Molecular mechanisms and therapeutic implications in osteoarthritis. AB - Dehydroepiandrosterone (DHEA), a 19-carbon steroid hormone primarily synthesized in the adrenal gland, exerts a chondroprotective effect against osteoarthritis (OA) and has been considered an effective candidate of disease-modifying OA drugs (DMOADs) that slow disease progression. We and others previously demonstrated that DHEA exerted a beneficial effect on osteoarthritic cartilage by positively modulating the balance between anabolic and catabolic factors (e.g., MMPs/TIMP-1, ADAMTS/TIMP-3 and cysteine proteinases/cystatin C), inhibiting catabolic signaling pathways (e.g., Wnt/beta-catenin), and suppressing proinflammatory cytokines-mediated low-grade synovial inflammation (e.g., IL-1beta). However, the full picture of the pharmacological molecular mechanism(s) underlying the activity of DHEA against OA is still incomplete, and a comprehensive and up-to date review article in this field is unavailable. In this review, recent findings (apart from the well documented pathogenesis of OA) regarding disease-related mechanisms involving low grade synovial inflammation, cartilage matrix stiffness, chondrocyte autophagy and the roles of a variety of catabolic cellular signaling pathways are discussed. Moreover, the possible relationship between these disease related mechanisms and DHEA action is discussed. Emerging evidence from in vivo and in vitro studies were scrutinized and are concisely presented to demonstrate the investigational and putative mechanisms underlying the anti-OA potential of DHEA. PMID- 29787834 TI - Structure and mechanism of bacterial tripartite efflux pumps. AB - Efflux pumps are membrane proteins which contribute to multi-drug resistance. In Gram-negative bacteria, some of these pumps form complex tripartite assemblies in association with an outer membrane channel and a periplasmic membrane fusion protein. These tripartite machineries span both membranes and the periplasmic space, and they extrude from the bacterium chemically diverse toxic substrates. In this chapter, we summarise current understanding of the structural architecture, functionality, and regulation of tripartite multi-drug efflux assemblies. PMID- 29787837 TI - Comment on "Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma". PMID- 29787835 TI - The expression of the genes involved in leucine catabolism of Pseudomonas aeruginosa is controlled by the transcriptional regulator LiuR and by the CbrAB/Crc system. AB - Pseudomonas aeruginosa metabolizes leucine through the leucine/isovalerate utilization pathway, whose enzymes are encoded in the liuRABCDE gene cluster (liu). In this study, we investigated the role of the LiuR protein in the liu cluster regulation. Our results indicated that liu expression is regulated at the transcriptional level by LiuR. Mobility shift assays using purified recombinant His-tagged LiuR showed that it was able to bind at the promoter region of liuR, in a dose-dependent manner. Results revealed that expression of the liu operon is subjected to carbon catabolite repression control (CCR); protein LiuD was strongly expressed in the presence of leucine, but it was repressed in the presence of glucose or succinate. Furthermore, this CCR control was dependent on LiuR as in the liuR- mutant the LiuD protein was strongly expressed in all the carbon sources tested. In agreement with this result, in the absence of the Crc protein, LiuD was expressed independently of the carbon source used, whereas in a cbrB- mutant its expression was severely impaired. The results indicated that the liu cluster is subjected to a coordinated transcriptional and translational regulation by the LiuR repressor and by the CbrAB/Crc system, respectively, in response to the available carbon source. PMID- 29787838 TI - Optimal Surgical Modality for Early Merkel Cell Carcinoma-Results from the National Cancer Data Base. PMID- 29787836 TI - Increased severity and epidermal alterations in persistent versus evanescent skin lesions in adult-onset Still disease. PMID- 29787839 TI - Reply to: "Comment on 'Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma'". PMID- 29787840 TI - Cutaneous features and diagnosis of primary Sjogren syndrome: An update and review. AB - Sjogren syndrome (SS) is an autoimmune connective tissue disorder (CTD) that principally affects the lacrimal and salivary glands. Although SS is 1 of the 3 most common autoimmune CTDs alongside systemic lupus erythematosus and progressive systemic sclerosis, it is the least researched CTD overall. SS poses a particular diagnostic challenge because it shares multiple clinical and immunologic features with other CTDs. However, there are some characteristic cutaneous clinical features that can precede the well-known sicca symptoms by years. By familiarizing themselves with these clinical features and having a high suspicion for SS, dermatologists can play an important role in the early diagnosis and treatment of this disease. PMID- 29787842 TI - Mesotherapy with Botulinum toxin for the treatment of refractory vascular and papulopustular rosacea. PMID- 29787841 TI - Undifferentiated pleomorphic sarcoma: Factors predictive of adverse outcomes. AB - BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) encompasses rare neoplasms that can arise either in the dermis or in the subfascial soft tissue. The behavior of UPS ranges from indolent to aggressive, but data predicting outcomes are limited. OBJECTIVE: Identify predictors of poor outcomes by analyzing a large collection of UPS cases. METHODS: We evaluated all available cases of UPS (including those termed atypical fibroxanthoma, malignant fibrous histiocytoma, pleomorphic dermal sarcoma, and subfascial UPS) across 3 tertiary care centers. RESULTS: Among the 319 patients, 45 experienced recurrence, 33 experienced metastasis, and 96 died of any cause. Risk factors for recurrence were clinical tumor size larger than 5 cm and invasion beyond subcutaneous fat. Risk factors for distant metastases were tumor site, tumor size larger than 2 cm, invasion beyond subcutaneous fat, and lymphovascular invasion. Risk factors for overall mortality were age, immunosuppression, tumor size larger than 2 cm, and lymphovascular invasion. History of skin cancer was associated with a lower risk of recurrence and metastasis. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Using the unbiased approach of pooling all UPS cases regardless of terminology, we identified clinical and histologic factors predicting poor outcomes. We propose subcategorization of UPS (into superficial versus deep UPS), which is consistent with the American Joint Committee on Cancer staging of soft tissue sarcoma. PMID- 29787843 TI - Adalimumab alleviates skin pain in patients with moderate-to-severe hidradenitis suppurativa: Secondary efficacy results from the PIONEER I and PIONEER II randomized controlled trials. PMID- 29787844 TI - Relative survival analysis in patients with stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery or wide local excision. PMID- 29787845 TI - Teaching pediatric dermoscopy in a resource-limited setting. PMID- 29787846 TI - Chemical study, antioxidant, anti-hypertensive, and cytotoxic/cytoprotective activities of Centaurea cyanus L. petals aqueous extract. AB - This study aimed to optimise the experimental conditions of extraction of the phytochemical compounds and functional properties of Centaurea cyanus petals. The following parameters were determined: the chemical composition (LC-ESI-MS/MS), the effects of pH on the stability and antioxidant activity of anthocyanins, the inhibition of lipid peroxidation, antioxidant activity, anti-hemolytic activity, antimicrobial, anti-hypertensive, and cytotoxic/cytoprotective effect, and the measurements of intracellular reactive oxygen species. Results showed that the temperature and time influenced (p <= 0.05) the content of flavonoids, anthocyanins, and FRAP. Only the temperature influenced the total phenolic content, non-anthocyanin flavonoids, and antioxidant activity (DPPH). The statistical approach made it possible to obtain the optimised experimental extraction conditions to increase the level of bioactive compounds. Chlorogenic, caffeic, ferulic, and p-coumaric acids, isoquercitrin, and coumarin were identified as the major compounds in the optimised extract. The optimised extract presented anti-hemolytic and anti-hypertensive activity in vitro, in addition to showing stability and reversibility of anthocyanins and antioxidant activity with pH variation. The C. cyanus petals aqueous extract exhibited high IC50 and GI50 (>900 MUg/mL) values for all cell lines, meaning low cytotoxicity. Based on the stress oxidative assay, the extract exhibited pro-oxidant action (10-100 MUg/mL) but did not cause damage or cell death. PMID- 29787847 TI - Leaves and stem bark from Allophylus africanus P. Beauv.: An approach to anti inflammatory properties and characterization of their flavonoid profile. AB - The small tree Allophylus africanus, widespread in the African continent, has long been considered valuable, as noted by the number of reports on their multiple medicinal uses. With this work, we aimed to extend the current, and so far restricted, knowledge on the chemical composition of the plant, particularly as source of flavonoids, as well as to assess its potential anti-inflammatory properties. The chemical characterization of the aqueous extract obtained from the leaves allowed the identification and quantitation of 30 flavones, predominantly apigenin derivatives, but also four luteolin derivatives, while the stem bark extract was solely characterized by apigenin di-C-glycosides and mono-C glycosides-O-glycosylated. Strong inhibitory effects towards 5-lipoxygenase were observed with the aqueous extracts obtained from the leaves and stem bark, with IC50 values of 41.28 and 107.77 MUg mL-1, respectively. Both extracts were also found to reduce NO levels in LPS-challenged RAW 264.7 macrophages, without noticeable cytotoxicity. The flavonoid profile of the plant is disclosed for the first time, allowing the identification of several molecules that may contribute to mitigate the inflammatory response. Jointly, with the current study the anti inflammatory use of the leaves and stem bark is partially validated. PMID- 29787849 TI - Application of prickly pear fruit extract to improve domestic shelf life, quality and microbial safety of sliced beef. AB - The research aimed to expand the knowledge on the use of natural bioactive compounds for food preservation. First-crop fruit of prickly pear were subjected to water extraction and evaluated for total polyphenol content, antioxidant activity, in vitro antimicrobial performance against food spoilage and pathogenic bacteria, and betacyanin and betaxanthin content. The extract was then applied by dipping technique to packed sliced beef, to evaluate its effect on physical and chemical parameters, color and texture maintenance, as well as on microbial growth during shelf life at domestic storage conditions. The in vitro antimicrobial assay of prickly pear fruit extract evidenced a wide spectrum activity, since it inhibited the growth of all Gram positive and negative targeted strains. In vivo application of extract effectively reduced microbial growth during refrigerated storage; total mesophilic count was maintained below the limit established by Commission Regulation (EC) No 2073/2005 of 5 * 106 log CFU/g of beef up to 8 d, in comparison to control sample that reached the mentioned limit after 4 d. Moreover, extract addition preserved beef color and texture over the considered storage period, supporting the potential prospect to utilize the extract to improve overall quality and to prolong domestic shelf life of sliced beef. PMID- 29787848 TI - Effects of steaming on contaminants of emerging concern levels in seafood. AB - Seafood consumption is a major route for human exposure to environmental contaminants of emerging concern (CeCs). However, toxicological information about the presence of CeCs in seafood is still insufficient, especially considering the effect of cooking procedures on contaminant levels. This study is one among a few who evaluated the effect of steaming on the levels of different CeCs (toxic elements, PFCs, PAHs, musk fragrances and UV-filters) in commercially relevant seafood in Europe, and estimate the potential risks associated with its consumption for consumers. In most cases, an increase in contaminant levels was observed after steaming, though varying according to contaminant and seafood species (e.g. iAs, perfluorobutanoate, dibenzo(ah)anthracene in Mytilus edulis, HHCB-Lactone in Solea sp., 2-Ethylhexyl salicylate in Lophius piscatorius). Furthermore, the increase in some CeCs, like Pb, MeHg, iAs, Cd and carcinogenic PAHs, in seafood after steaming reveals that adverse health effects can never be excluded, regardless contaminants concentration. However, the risk of adverse effects can vary. The drastic changes induced by steaming suggest that the effect of cooking should be integrated in food risk assessment, as well as accounted in CeCs regulations and recommendations issued by food safety authorities, in order to avoid over/underestimation of risks for consumer health. PMID- 29787850 TI - RIFM fragrance ingredient safety assessment 2-methyl-trans-2-butenoic acid, CAS Registry Number 80-59-1. PMID- 29787852 TI - Evaluating the Construct Validity of a Pulsatile Fresh Frozen Human Cadaver Circulation Model for Endovascular Training. AB - BACKGROUND: We recently described a pulsatile fresh frozen human cadaver model (PHCM) for training endovascular practitioners. This present study aims to assess the construct validity of PHCM; its ability to differentiate between participants of varying expertise. METHODS: Twenty-three participants with varying endovascular experience (12 novice, 4 intermediate, and 7 expert) were recruited. Each attempted catheterization of the left renal artery on PHCM within 10 min under exam conditions. Performances were video recorded and scored using a validated scoring tool by 2 independent endovascular experts, blinded to performer status. Each participant was given a task-specific checklist score (TSC), global rating score (GRS), and overall procedure score (OPS). Finally, examiners were asked whether they would be happy to supervise the participant in theater, with each participant graded as "fail", "borderline," or "pass". RESULTS: All expert and intermediate participants completed the index procedure within the allotted 10 min; however, only one of the 12 novice participants achieved this (P < 0.0005). Endovascular novices had significantly lower TSC, GRS, and OPS than both intermediate participants and endovascular experts. There were no significant differences in TSC, GRS, or OPS between intermediate participants and endovascular experts. When participants were graded as "fail", "borderline," or "pass," there were significant differences between groups (P = 0.001). All of the intermediate and expert participants received a pass. Out of the 12 novice participants, 2 received a pass, 6 received a borderline, and 4 were failed. CONCLUSIONS: The PHCM demonstrates construct validity. Further work is required to determine its educational impact in endovascular training. PMID- 29787853 TI - False Aneurysm of the Popliteal Artery Complicated by a Deep Venous Thrombosis Revealing an Exostosis in a 20-Year-Old Woman. AB - Exostoses or osteochondromas are benign osseous tumors that develop on the bone surface and can be sporadic or hereditary. Their evolution is generally benign, but they may be complicated in some patients by conflicts with the surrounding nervous or vascular structures, in particular arteries. We report a case of false aneurysm of the popliteal artery secondary to an isolated exostosis of the left femur in a 20-year-old woman. A delay in the diagnosis allowed the development of the false aneurysm, which was at the origin of a major venous compression. The surgical treatment consisted in aneurysmectomy and reconstruction by end-to-end anastomosis associated with the resection of the osseous tumor, and the deep venous thrombosis was treated medically. PMID- 29787851 TI - Jetlag related sleep problems and their management: A review. AB - OBJECTIVES: We reviewed Jetlag, particularly in view of its effects on sleep and how it can be managed. METHODS: The Proquest Central database of Kirikkale University, PubMed and Google scholar were used while searching for the following key words: "Jetlag", "symptoms", "sleep", "melatonin" and "treatment". RESULTS: Flight dysrhythmia, otherwise known as jetlag, is caused by flying globally over various time zones. Most passengers who fly over six or more different time zones generally require 4-6 days after travelling to resume their usual sleep patterns and to feel less lethargic during the day. Signs of jet lag can vary between debilitated awareness, insomnia, feeling tired during the day and frequent waking during the night. During the night our pineal glands excrete a hormone called melatonin; dim lights cause the continuation of excretion of these hormones whereas any exposure to bright lights stems the flow of release. Common precautionary measures are specific diets, bright lights and melatonin agonists (Ramelteon, Agomelatine). CONCLUSION: Sleep issues derived from jetlag were found to be most common in passengers who flew through various time belts. Melatonin assumes a critical part in adjusting the body's circadian rhythms and has been utilized restoratively to re-establish irritated circadian rhythms. PMID- 29787854 TI - The Role of Duplex Ultrasound in Detecting Graft Thrombosis and Endoleak after Endovascular Aortic Repair for Abdominal Aneurysm. AB - BACKGROUND: To assess the role of duplex ultrasound (DUS) in detecting endoleaks (ELs) and graft thrombosis (GT) in a cohort of patients submitted to endovascular aortic repair (EVAR) for elective infrarenal abdominal aortic aneurysm (AAA) in 2 centers. METHODS: Data, of all consecutive patients treated in 2 operative units of vascular surgery, from January 01, 2000 to December 31, 2016, were retrospectively collected and evaluated. Follow-up data were analyzed to evaluate survival and device-related complications, both at 30-day and in the midterm. The results of computed tomography angiography (CTA) and DUS which were performed yearly, with a time interval between the 2 examinations lower than 30 days, were paired in terms of maximum transverse diameters of the aneurysmal sac, identification of EL, and of GT. Sensibility (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) of the DUS were calculated with respect to data of each paired CTA and to data of the real clinical diagnosis of either EL or GT. A Student's t-test was performed to compare the aneurysmal sac diameters measured with DUS to those of CTA. "Kappa" coefficient of agreement was also calculated. A P value < 0.05 was the level reference for statistical significance. RESULTS: A total of 920 patients (104 female, 11.3%) underwent EVAR for elective infrarenal AAA. Technical success was achieved in 910 cases (98.9%). At 30 days, there were 5 deaths (0.5%), no GT, and 3 small type II ELs which did not require any adjunctive procedure. Mean follow-up was 64.8 months (range 1-120.3 months). Survival and freedom from complications were estimated to be 78.4% +/- 1.9% and 48.3% +/- 1.7%, respectively, at 10 years. Seventy-six more ELs and 8 GTs were recorded. Considering the CTA as the gold standard, SE, SP, and ACC of DUS in the detection of the EL were 93.2% +/- 5.8%, 98.8% +/- 1.1%, and 97.8%, respectively, with a PPV of 94.5% +/- 5.2% and a NPV of 98.3% +/- 1.4%. Considering, however, the real diagnosis of the EL, SE, SP, and ACC of DUS were slightly lower (89.4% +/- 6.9%, 98.5% +/- 1.3%, and 96.9%, respectively), as well as PPV and NPV (93.1% +/- 5.8% and 97.7% +/- 1.6%, respectively). K coefficient of agreement between the measurements of the sac maximum transverse diameter recorded at DUS and CTA was 0.91, with a little underestimation of the aneurysm diameter at DUS if compared with CTA (mean diameter difference of 2.5 mm, 95% confidence interval: 2.25-2.75 mm). CONCLUSIONS: DUS has proven to be a reliable examination in identifying all GT and most ELs after EVAR, compared with CTA. A good correlation was also observed between the measurements of the sac maximum transverse diameter recorded at DUS and CTA, with a little underestimation of the aneurysm diameter at DUS compared with CTA. PMID- 29787855 TI - Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders. AB - Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice. L. reuteri, a species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. In addition, L. reuteri treatment affected GABA receptor gene expression and protein levels in multiple brain regions. This study identifies bacterial species that are sensitive to an autism related mutation, and further suggests a therapeutic potential for probiotic treatment. PMID- 29787856 TI - The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis. AB - Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score >=18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [>=3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA. PMID- 29787857 TI - High-fructose diet during adolescent development increases neuroinflammation and depressive-like behavior without exacerbating outcomes after stroke. AB - Diseases, disorders, and insults of aging are frequently studied in otherwise healthy animal models despite rampant co-morbidities and exposures among the human population. Stressor exposures can increase neuroinflammation and augment the inflammatory response following a challenge. The impact of dietary exposure on baseline neural function and behavior has gained attention; in particular, a diet high in fructose can increase activation of the hypothalamic-pituitary adrenal axis and alter behavior. The current study considers the implications of a diet high in fructose for neuroinflammation and outcomes following the cerebrovascular challenge of stroke. Ischemic injury may come as a "second hit" to pre-existing metabolic pathology, exacerbating inflammatory and behavioral sequelae. This study assesses the neuroinflammatory consequences of a peri adolescent high-fructose diet model and assesses the impact of diet-induced metabolic dysfunction on behavioral and neuropathological outcomes after middle cerebral artery occlusion. We demonstrate that consumption of a high-fructose diet initiated during adolescent development increases brain complement expression, elevates plasma TNFalpha and serum corticosterone, and promotes depressive-like behavior. Despite these adverse effects of diet exposure, peri adolescent fructose consumption did not exacerbate neurological behaviors or lesion volume after middle cerebral artery occlusion. PMID- 29787859 TI - Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. DESIGN: In a randomised double-blind placebo controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. METHODS: Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640. PMID- 29787860 TI - Tissue transplantation in planarians: A useful tool for molecular analysis of pattern formation. AB - Freshwater planarians are well known for their remarkable plasticity and regenerative capabilities. Most studies of planarian regeneration have specifically examined regeneration after transverse or longitudinal sectioning or during homeostasis in intact adults. However, tissue transplantation, first performed over a century ago, constitutes another important tool in the study of regeneration in planarians, and can be easily performed given this species' extraordinary healing capacity and its lack of a circulatory system. Studies conducted to date have demonstrated the viability of transplantations involving a variety of tissue types of different positional identities, affecting any of the 3 main body axes. Moreover, these grafting experiments have shown that tissues possess axial positional identities, which are retained following transplantation. The confrontation between different positional identities that occurs after any type of tissue transplantation is resolved by the formation of a blastema, consisting of undifferentiated tissue produced by adult pluripotent stem cells (neoblasts). This blastema intercalates the positional identities of the graft and host tissues. The recent discovery of pathways involved in planarian growth, patterning, and organogenesis, as well as corresponding molecular markers, makes tissue transplantation a vital new tool with which to explore pattern formation. Here, we discuss the different grafting approaches used in planarians, and the corresponding intercalary regenerative response, placing particular emphasis on the respective contributions of donor and host tissue. Moreover, we discuss the temporal induction of blastema formation, and present new molecular data on the generation of an ectopic anterior/posterior axis in response to dorsal/ventral confrontations between host and donor tissue. PMID- 29787861 TI - Morphological homeostasis in the fossil record. AB - Morphological homeostasis limits the extent to which genetic and/or environmental variation is translated into phenotypic variation, providing generation-to generation fitness advantage under a stabilizing selection regime. Depending on its lability, morphological homeostasis might also have a longer-term impact on evolution by restricting the variation-and thus the response to directional selection-of a trait. The fossil record offers an inviting opportunity to investigate whether and how morphological homeostasis constrained trait evolution in lineages or clades on long timescales (thousands to millions of years) that are not accessible to neontological studies. Fossils can also reveal insight into the nature of primitive developmental systems that might not be predictable from the study of modern organisms. The ability to study morphological homeostasis in fossils is strongly limited by taphonomic processes that can destroy, blur, or distort the original biological signal: genetic data are unavailable; phenotypic data can be modified by tectonic or compaction-related deformation; time averaging limits temporal resolution; and environmental variation is hard to study and impossible to control. As a result of these processes, neither allelic sensitivity (and thus genetic canalization) nor macroenvironmental sensitivity (and thus environmental canalization) can be unambiguously assessed in the fossil record. However, homeorhesis-robustness against microenvironmental variation (developmental noise)-can be assessed in ancient developmental systems by measuring the level of fluctuating asymmetry (FA) in a nominally symmetric trait. This requires the analysis of multiple, minimally time-averaged samples of exquisite preservational quality. Studies of FA in fossils stand to make valuable contributions to our understanding of the deep-time significance of homeorhesis. Few empirical studies have been conducted to date, and future paleontological research focusing on how homeorhesis relates to evolutionary rate (including stasis), species survivorship, and purported macroevolutionary trends in evolvability would reap high reward. PMID- 29787858 TI - A randomized clinical trial of counseling and nicotine replacement therapy for treatment of African American non-daily smokers: Design, accrual, and baseline characteristics. AB - BACKGROUND: Non-daily smokers (NDS) who smoke on some but not all days are a growing subset of United States (US) tobacco users. Racial/ethnic minorities are more likely to be NDS. African American NDS have strikingly high levels of nicotine and carcinogen exposure, making treatment of this high risk group a priority. METHODS: The current study is one of three ongoing federally-funded clinical trials of NDS and, to our knowledge the only RCT focused on racial/ethnic minority NDS. The design has been guided by input from Patient and Stakeholder Advisory Panels who helped develop the research questions, design the intervention, and select the outcomes. The objective is to compare the effectiveness of smoking cessation counseling alone (C) or smoking cessation counseling plus participant's choice of nicotine replacement therapy (NRT; C + NRT) for African American NDS. Two-hundred seventy-eight African American NDS will be randomized in a 2:1 fashion to C + NRT or C. All participants receive five sessions of smoking cessation counseling; those randomized to C + NRT receive their choice of nicotine gum, patch, and/or lozenge. Treatment in both groups lasts for 12 weeks. We hypothesize that C + NRT will be more effective than C on the primary outcome of biochemically-confirmed abstinence from smoking at week 12. Secondary aims will compare C + NRT and C on patient- and provider desired outcomes including abstinence from smoking at week 26, change in biochemically-verified nicotine and carcinogen exposure, days abstinent, and treatment process measures (e.g., NRT use and side effects). Predictors of abstinence will also be explored. DISCUSSION: Findings will illuminate effective treatment options for African American NDS and contribute to development of evidence-based guidelines for treating the 8.9 million US adult NDS for whom no guidelines currently exist. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02244918. PMID- 29787862 TI - Multiple modes of canalization: Links between genetic, environmental canalizations and developmental stability, and their trait-specificity. AB - The robustness of biological systems against mutational and environmental perturbations is termed canalization. Because reducing phenotypic variability under environmental and genetic perturbations can be adaptive and facilitated by natural selection, it has been suggested that once canalization mechanisms have evolved to buffer the effects of environmental perturbations, they may act to buffer any and all sources of variation. Although whether canalization mechanisms are general or specific to the types of perturbation or phenotypic traits that they buffer is often addressed, the links between different canalization mechanisms remain unclear. In this review, three major sources of phenotypic variation, associated canalization concepts and indicators of the degree of canalization are first outlined. Then, the molecular bases of canalization mechanisms based on recent empirical studies are overviewed. Finally, the links between the underlying processes of different canalization mechanisms are explored. PMID- 29787863 TI - Validity of Targeted Next-Generation Sequencing in Routine Care for Identifying Clinically Relevant Molecular Profiles in Non-Small-Cell Lung Cancer: Results of a 2-Year Experience on 1343 Samples. AB - Theranostic assays are based on single-gene testing, but the ability of next generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non-small-cell lung cancers (n = 1343). The R2 correlation between expected and measured allelic ratio, using commercial samples, was >0.96. Mutation detection threshold was 2% for 10 ng of DNA input. kappa Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97-1.00) for EGFR and 0.98 (95% CI, 0.97-1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associations were found between EGFR and PI3KCA or CTNNB1 and between KRAS and STK11. Potential oncogenic driver mutations or gene amplifications were more frequent in validated oncogenic driver nonmutated samples. This work is a proof of concept that targeted NGS is accessible in routine screening, including large screening, at reasonable cost. Clinical data should be collected and implemented in specific databases to make molecular data meaningful for direct patients' benefit. PMID- 29787864 TI - The neonatal brain in critical congenital heart disease: Insights and future directions. AB - Neurodevelopmental outcomes are impaired in survivors of critical congenital heart disease (CHD) in several developmental domains including motor, cognitive and sensory outcomes. These deficits can extend into the adolescent and early adulthood years. The cause of these neurodevelopmental impairments is multi factorial and includes patient specific risk factors, cardiac anatomy and physiology as well as brain changes seen on MRI. Advances in imaging techniques have identified delayed brain development in the neonate with critical CHD as well as acquired brain injury. These abnormalities are seen even before corrective neonatal cardiac surgery. This review focuses on describing brain changes seen on MRI in neonates with CHD, risk factors for these changes and the association with neurodevelopmental outcome. There is an emerging focus on the impact of cardiovascular physiology on brain health and the complex heart-brain interplay that influences ultimate neurodevelopmental outcome in these patients. PMID- 29787865 TI - A comparison of three fiber tract delineation methods and their impact on white matter analysis. AB - Diffusion magnetic resonance imaging (dMRI) is an important method for studying white matter connectivity in the brain in vivo in both healthy and clinical populations. Improvements in dMRI tractography algorithms, which reconstruct macroscopic three-dimensional white matter fiber pathways, have allowed for methodological advances in the study of white matter; however, insufficient attention has been paid to comparing post-tractography methods that extract white matter fiber tracts of interest from whole-brain tractography. Here we conduct a comparison of three representative and conceptually distinct approaches to fiber tract delineation: 1) a manual multiple region of interest-based approach, 2) an atlas-based approach, and 3) a groupwise fiber clustering approach, by employing methods that exemplify these approaches to delineate the arcuate fasciculus, the middle longitudinal fasciculus, and the uncinate fasciculus in 10 healthy male subjects. We enable qualitative comparisons across methods, conduct quantitative evaluations of tract volume, tract length, mean fractional anisotropy, and true positive and true negative rates, and report measures of intra-method and inter method agreement. We discuss methodological similarities and differences between the three approaches and the major advantages and drawbacks of each, and review research and clinical contexts for which each method may be most apposite. Emphasis is given to the means by which different white matter fiber tract delineation approaches may systematically produce variable results, despite utilizing the same input tractography and reliance on similar anatomical knowledge. PMID- 29787866 TI - Handedness-dependent functional organizational patterns within the bilateral vestibular cortical network revealed by fMRI connectivity based parcellation. AB - Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole brain RSN (P-to-RSN). This approach disclosed handedness-dependency, inter hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples. PMID- 29787867 TI - Investigating common coding of observed and executed actions in the monkey brain using cross-modal multi-variate fMRI classification. AB - Mirror neurons are generally described as a neural substrate hosting shared representations of actions, by simulating or 'mirroring' the actions of others onto the observer's own motor system. Since single neuron recordings are rarely feasible in humans, it has been argued that cross-modal multi-variate pattern analysis (MVPA) of non-invasive fMRI data is a suitable technique to investigate common coding of observed and executed actions, allowing researchers to infer the presence of mirror neurons in the human brain. In an effort to close the gap between monkey electrophysiology and human fMRI data with respect to the mirror neuron system, here we tested this proposal for the first time in the monkey. Rhesus monkeys either performed reach-and-grasp or reach-and-touch motor acts with their right hand in the dark or observed videos of human actors performing similar motor acts. Unimodal decoding showed that both executed or observed motor acts could be decoded from numerous brain regions. Specific portions of rostral parietal, premotor and motor cortices, previously shown to house mirror neurons, in addition to somatosensory regions, yielded significant asymmetric action specific cross-modal decoding. These results validate the use of cross-modal multi-variate fMRI analyses to probe the representations of own and others' actions in the primate brain and support the proposed mapping of others' actions onto the observer's own motor cortices. PMID- 29787869 TI - Shear stress sensitizes TRPV4 in endothelium-dependent vasodilatation. AB - The aim of this study was to better understand the role of TRPV4 in the regulation of blood vessel dilatation by blood flow and activation of GPCRs. Using pressure myography, the dilator responses to the TRPV4 agonist GSK1016790A and to acetylcholine, were examined in rat cremaster arterioles exposed to either no shear stress or to 200 MUl/min flow for 6 min. In control vessels GSK1016709A caused vasodilatation (pEC50 7.73 +/- 0.12 M, DeltaDmax 97 +/- 3%) which was significantly attenuated by the TRPV4 antagonists GSK2193874 (100 nM) (pEC50 6.19 +/- 0.11 M, p < 0.05) and HC067047 (300 nM) (pEC50 6.44 +/- 0.12 M) and abolished by removal of the endothelium. Shear conditioned arterioles were significantly more sensitive to GSK1016790A (pEC50 8.34 +/- 0.11, p < 0.05). Acetylcholine induced vasodilatation (pEC50 7.02 +/- 0.07 M, DeltaDmax 93 +/- 2%) was not affected by shear forces (pEC50 7.08 +/- 0.07 M, DeltaDmax 95 +/- 1%). The dilator response to acetylcholine was unaffected by the TRPV4 antagonist GSK2193874 in control arterioles (pEC50 7.24 +/- 0.07 M, DeltaDmax 97 +/- 2%). However, in shear treated arterioles, the acetylcholine-response was significantly attenuated by GSK2193874 (pEC50 6.25 +/- 0.12 M, p < 0.05) indicating an induced interaction between TRPV4 and muscarinic receptors. TRPV4 antibodies localized TRPV4 to the endothelium and shear stress had no effect on its localisation. Finally, agonist activation of the M3 muscarinic receptor opened TRPV4 in HEK293 cells. We concluded that shear stress increases endothelial TRPV4 agonist sensitivity and links TRPV4 activation to muscarinic receptor mediated endothelium-dependent vasodilatation, providing strong evidence that blood flow modulates downstream signalling from at least one but not all GPCRs expressed in the endothelium. PMID- 29787868 TI - Individualized tractography-based parcellation of the globus pallidus pars interna using 7T MRI in movement disorder patients prior to DBS surgery. AB - The success of deep brain stimulation (DBS) surgeries for the treatment of movement disorders relies on the accurate placement of an electrode within the motor portion of subcortical brain targets. However, the high number of electrodes requiring relocation indicates that today's methods do not ensure sufficient accuracy for all patients. Here, with the goal of aiding DBS targeting, we use 7 Tesla (T) MRI data to identify the functional territories and parcellate the globus pallidus pars interna (GPi) into motor, associative and limbic regions in individual subjects. 7 T MRI scans were performed in seventeen patients (prior to DBS surgery) and one healthy control. Tractography-based parcellation of each patient's GPi was performed. The cortex was divided into four masks representing motor, limbic, associative and "other" regions. Given that no direct connections between the GPi and the cortex have been shown to exist, the parcellation was carried out in two steps: 1) The thalamus was parcellated based on the cortical targets, 2) The GPi was parcellated using the thalamus parcels derived from step 1. Reproducibility, via repeated scans of a healthy subject, and validity of the findings, using different anatomical pathways for parcellation, were assessed. Lastly, post-operative imaging data was used to validate and determine the clinical relevance of the parcellation. The organization of the functional territories of the GPi observed in our individual patient population agrees with that previously reported in the literature: the motor territory was located posterolaterally, followed anteriorly by the associative region, and further antero-ventrally by the limbic territory. While this organizational pattern was observed across patients, there was considerable variability among patients. The organization of the functional territories of the GPi was remarkably reproducible in intra-subject scans. Furthermore, the organizational pattern was observed consistently by performing the parcellation of the GPi via the thalamus and via a different pathway, going through the striatum. Finally, the active therapeutic contact of the DBS electrode, identified with a combination of post-operative imaging and post-surgery DBS programming, overlapped with the high-probability "motor" region of the GPi as defined by imaging-based methods. The consistency, validity, and clinical relevance of our findings have the potential for improving DBS targeting, by increasing patient-specific knowledge of subregions of the GPi to be targeted or avoided, at the stage of surgical planning, and later, at the stage when stimulation is adjusted. PMID- 29787870 TI - Oral hydroxysafflor yellow A reduces obesity in mice by modulating the gut microbiota and serum metabolism. AB - Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our results showed that the average body weight of HF group treated by HSYA was significantly lower than that of the HF group (P < 0.01). HSYA also reduced fat accumulation, ameliorated insulin resistance, restored glucose homeostasis, reduced inflammation, enhanced intestinal integrity, and increased short-chain fatty acids (SCFAs) production in HF diet-fed mice. Sequencing of 16S rRNA genes in fecal samples demonstrated that HSYA reversed HF diet induced gut microbiota dysbiosis. Particularly, HSYA increased the relative abundances of genera Akkermansia and Romboutsia, as well as SCFAs-producing bacteria, including genera Butyricimonas and Alloprevotella, whereas it decreased the phyla Firmicutes/Bacteroidetes ratio of HF diet-fed mice. Additionally, serum metabolomics analysis revealed that HSYA increased lysophosphatidylcholines (lysoPCs), L-carnitine and sphingomyelin, and decreased phosphatidylcholines in mice fed a HF diet, as compared to HF group. These changed metabolites were mainly linked with the pathways of glycerophospholipid metabolism and sphingolipid metabolism. Spearman's correlation analysis further revealed that Firmicutes was positively while Bacteroidetes and Akkermansia were negatively correlated with body weight, fasting serum glucose and insulin. Moreover, Akkermansia and Butyricimonas had positive correlations with lysoPCs, suggestive of the role of gut microbiota in serum metabolites. Our findings suggest HSYA may be a potential therapeutic drug for obesity and the gut microbiota may be potential territory for targeting of HSYA. PMID- 29787871 TI - Spontaneous Intracerebral Hemorrhage in a Plateau Area: A Study Based on the Tibetan Population. AB - OBJECTIVE: To reveal the characteristics of spontaneous intracerebral hemorrhage (sICH) in a plateau area based on the Tibetan population. METHODS: Data of Tibetan and Han patients (control group) with sICH treated at our center from January 2013 to April 2017 were retrospectively reviewed. RESULTS: A total of 122 Tibetan and 927 Han patients were included. Compared with Han patients, Tibetan patients were older (54.7 +/- 11.2 vs. 50.9 +/- 18.3 years, P = 0.027), exhibited higher male-to-female ratios (73.8% vs. 55.0%, P < 0.001), were more overweight (22.1% vs. 13.1%, P = 0.007) had more smokers (36.9% vs. 20.5%, P < 0.001), had a higher concentration of hemoglobin (163.7 +/- 17.6 vs. 134.8 +/- 20.2 g/L, P < 0.001), and included a higher number of patients with hypertension (83.6% vs. 60.5%, P < 0.001), diabetes mellitus (19.2% vs. 9.3%, P = 0.002), and prior hemorrhagic stroke (9.0% vs. 2.0%, P < 0.001). Tibetan patients also experienced more brainstem hemorrhage (11.5% vs. 5.1%, P = 0.039) in the infratentorial region and had a higher risk of in-hospital complications resulting from hematoma enlargement (20.5% vs. 10.4%, P = 0.002) and cerebral infarction (59.0% vs. 9.7%, P < 0.001). During a 6-month follow-up period, they had higher rates of unfavorable outcomes and case mortality (P < 0.05). A multivariable analysis adjusted for confounding factors revealed that the Tibetan race was positively associated with unfavorable clinical outcomes in sICH patients (P < 0.05). CONCLUSIONS: Tibetan sICH patients from the plateau area presented unique characteristics in their baseline measurements, incidence of comorbidities, hematoma location, risk of in-hospital complications, and clinical outcomes compared with Han patients. The Tibetan race was positively associated with unfavorable 6-month outcomes in ICH patients. PMID- 29787872 TI - Development of a Preoperative Simulation Technique for Carotid Endarterectomy in Patients with Contrast Contraindications. AB - BACKGROUND: Vascular and osteological parameters, such as the heights of the carotid bifurcation and distal end of the plaque, are important preoperative considerations for patients undergoing carotid stenosis procedures, such as carotid endarterectomy. However, for patients with contraindications to contrast media, such as allergies or nephropathies, 3-dimensional computed tomography angiography (3D-CTA) is unavailable, and preoperative evaluation remains challenging. In the present study, we aimed to develop a preoperative simulation for use in patients with contrast-contraindicated carotid stenosis. METHODS: Images from noncontrast neck computed tomography scans and magnetic resonance imaging obtained without the Leksell stereotactic frame were uploaded to GammaPlan. Following delineation of various structures, preoperative simulations were performed to determine the relationships between vascular and osteological structures. We applied this technique in 10 patients with carotid stenosis to verify the accuracy of the simulation. RESULTS: In all patients, the GammaPlan simulation successfully visualized the heights of the carotid bifurcation and distal end of the plaque without the use of contrast medium. Furthermore, information regarding the location of internal arterial structures, such as calcifications and unstable plaques, could be incorporated into GammaPlan images. We verified simulation accuracy by comparing the simulation results with 3D-CTA and operative findings. CONCLUSIONS: Simulations created using GammaPlan can be used to obtain accurate vascular and osteological information regarding the heights of the carotid bifurcation and distal end of the plaque, without the use of contrast medium. The reconstruction of delineated structures using this technique may be effective for preoperative evaluation in patients with contrast contraindicated carotid stenosis. PMID- 29787873 TI - Transforaminal Endoscopic Decompression for Foot Drop 12 Years After Lumbar Total Disk Replacement. AB - Lumbar total disk replacement is considered for the treatment of lumbar degenerative disk disease with the hope that by preserving motion, the long-term fusion complication of adjacent segment disease can be avoided. The complications of lumbar total disk replacement can be divided into approach-related and long term complications. Little has been described about the complications and treatment for complications >10 years after the device has been implanted. Here we describe a transforaminal endoscopic diskectomy procedure for a patient presenting with foot drop 12 years after a L5-S1 total disk replacement. PMID- 29787874 TI - Ancient Observation of Spinal Cord Injury: The Case of the Assyrian Lion. AB - The description of paraplegia is considered a milestone in the history of neurology. The Egyptians provided excellent descriptions of spinal cord injuries, the Bible has several references to paraplegia, and, more recently, the pioneers of neurology described the classic syndromes related to spinal injuries and paraplegia. Here, we describe an ancient observation by the Assyrian people of paraplegia in an animal. In ancient Assyria, lion hunting was a ritualized activity conducted for political and religious purposes. The Lion Hunt of Ashurbanipal, a series of Assyrian palace reliefs from the North Palace at Nineveh dating from approximately 645 BCE, which is now in the British Museum in London, UK, shows King Ashurbanipal hunting lions. Applying modern knowledge of mammalian dermatomes to the images, we reveal a detailed and precise observation of paraplegia after spinal cord injury. PMID- 29787875 TI - Minimally Invasive Lateral Access Surgery and Reoperation Rates: A Multi Institution Retrospective Review of 2060 Patients. AB - BACKGROUND: Risk factors for surgical revision remain important because of additional readmission, anesthesia, and morbidity for the patient and significant cost for health care systems. Although the rate of reoperation (RRO) is well described for traditional open posterior (OP) approaches, the RRO in minimally invasive lateral (MIL) surgery remains poorly characterized. This study compares the RRO in patients undergoing decompressive lumbar spine surgery via MIL versus OP approaches. METHODS: Patient demographics and comorbidities were retrospectively collected for 2060 patients undergoing single-stage elective lumbar spinal surgery at multiple institutions. A subset of 1484 patients had long-term data (long-term cohort [LT cohort]). The RRO was compared between approaches through univariate and multivariate analysis. RESULTS: There were 1292 patients (62.7%) who underwent lateral access surgery, whereas 768 patients (37.3%) underwent OP surgery. The MIL cohort was significantly older, had a higher proportion of men, and had more comorbidities than the OP cohort. In the LT cohort, lateral patients were significantly older and had more comorbidities, with a lower body mass index and a lower proportion of men and smokers. Surgical complications between the groups trended to be similar. The MIL cohort had a significantly lower RRO at both 30 days (approximately 57% lower, MIL cohort: 1.01% vs. OP cohort: 2.36%, P = 0.02) and 2 years (approximately 61% lower, MIL cohort: 2.09% vs. OP cohort: 5.37%, P < 0.01) after surgery. On multivariate analysis, surgical approach was the only significant predictor for the RRO at both 30 days (open posterior approach odds ratio [OR], 4.47; 95% confidence interval [CI], 1.33-15.09; P = 0.02) and 2 years (open posterior approach OR, 3.26; 95% CI, 1.26-8.42; P = 0.01). CONCLUSIONS: This study shows that MIL surgical approaches, compared with OP approaches, have a significantly lower RRO after lumbar spine surgery. PMID- 29787876 TI - Risk Analysis Based on the Timing of Tracheostomy Procedures in Patients with Spinal Cord Injury Requiring Cervical Spine Surgery. AB - OBJECTIVE: To determine the optimal moment to perform tracheostomy in a patient requiring anterior cervical fixation. METHODS: A retrospective observational study conducted over an 18-year period included 56 patients who had been admitted to the intensive care unit with acute spinal cord injury and underwent tracheostomy and surgical fixation. The sample was divided into 2 groups: at-risk group (31 patients who had undergone tracheostomy before cervical surgery or <4 days after surgery) and not-at-risk group (25 patients who had undergone tracheostomy >4 days after fixation surgery). Descriptive and comparative studies were carried out. Overall trend of the collected data was analyzed using cubic splines (graphic methods). RESULTS: The only infectious complications diagnosed as related to the surgical procedure were infection of the surgical wound in 2 patients in the not-at-risk group (12%) and deep tissue infection in 1 patient in the at-risk group (3.2%). During the study period, we identified a tendency toward performance of early tracheostomies. CONCLUSIONS: Our results suggest that the presence of a tracheostomy stoma before or immediately after surgery is associated with a low risk of infection of the cervical surgical wound in instrumented spinal fusion. PMID- 29787877 TI - Anatomic Study of Superior Cluneal Nerves: Application to Low Back Pain and Surgical Approaches to Lumbar Vertebrae. AB - OBJECTIVE: The aim of this study was to investigate the anatomy of the superior cluneal nerves more proximal to the posterior layer of the thoracolumbar fascia. METHODS: Twelve sides of 6 fresh-frozen cadavers were used. The age at death ranged from 54 to 88 years. After a transverse skin incision 10 mm above the iliac crest, the superior cluneal nerves were detected by blunt dissection and traced back to the dorsal root ganglia. The diameter of the nerves from L1 to L3 was measured. Also, the relationship to the erector spinae muscle and dorsal ramus was recorded. RESULTS: The mean diameters of the origin of the L1, L2, and L3 were 1.71 +/- 0.29 mm, 1.73 +/- 0.40 mm, and 1.52 +/- 0.55 mm, respectively. On 7 sides (58.3%) for L1, seven sides (58.3%) for L2, and 10 sides (83.3%) for L3, the nerves pierced the iliocostalis muscle. One side (8.3%) for L2 and one (8.3%) for L3 had no cutaneous branch. CONCLUSIONS: The results of this study could help to elucidate the anatomy of the superior cluneal nerves and help avoid complications during surgical approaches to the lumbar spine. PMID- 29787878 TI - Gamma Knife Radiosurgery of the Superior Laryngeal Neuralgia: A Report of 3 Cases. AB - BACKGROUND: Superior laryngeal neuralgia (SLN) is a relatively rare disorder that is characterized by neck pain. There are only a few reported cases and treatment options for SLN to date. In this study, we report 3 patients with SLN who were treated with Gamma Knife radiosurgery (GKRS) at the time of diagnosis. CASE DESCRIPTION: For all 3 patients, GKRS was administered using a 4-mm collimator to deliver a single shot of 80 Gy of radiation (100% isodose line). The target was set at the jugular foramen where the vagus and glossopharyngeal nerves emerge from the skull. Follow-up assessments were performed at 32, 31, and 30 months after GKRS. The 3 patients described pain relief at 3 months, 2 days, and 6 weeks. None of the patients developed neurologic deficits during the follow-up period. CONCLUSIONS: This preliminary report provides encouraging evidence that GKRS represents an effective, safe, and relatively durable noninvasive treatment option for patients with SLN. PMID- 29787879 TI - Management of Pediatric Posttraumatic Thoracolumbar Vertebral Body Burst Fractures by Use of Single-Stage Posterior Transpedicular Approach. AB - PURPOSE: The posterior transpedicular approach (PTA) is a posterior approach that has the advantage of achieving circumferential arthrodesis by a single posterior only approach. The purpose of this study was to analyze our experience with PTA in the management of pediatric traumatic thoracolumbar burst fractures (TTLBFs). METHODS: Consecutive pediatric patients (age <=18 years) with TTLBFs treated with PTA for 6 years were included in this retrospective study. Correction of kyphotic deformity and change in neurologic status were analyzed to assess outcome. The Cobb angle and American Spinal Injury Association (ASIA) grade were used for this purpose. RESULTS: There were 6 male and 8 female patients. Five patients had complete injury (ASIA-A), and 9 had incomplete injury. The mean Thoracolumbar Injury Classification and Severity score was 6.71. The mean preoperative Cobb angle was 14.71 degrees and improved to -3.35 degrees postoperatively (mean kyphosis correction -18.05 degrees ). Two of the patients experienced iatrogenic nerve root injury. There was 1 postoperative mortality due to complications unrelated to the surgery. The mean Cobb angle was -0.07 degrees at the 32.2 month follow-up visit. Six patients experienced cage subsidence, but none required revision surgery. Postoperatively, 11 (78.5%) patients showed neurologic improvement, and none experienced deterioration. The average ASIA score improved from 2.5 to 3.78. A fusion rate of 100% (n = 12) was observed at the last follow up visit. CONCLUSIONS: The present study demonstrates that PTA is a feasible approach in selected pediatric patients with unstable traumatic thoracolumbar burst fractures, with results comparable with those in the adult population. This study demonstrates in detail the procedure, along with the neurologic and radiologic outcomes of this approach in the pediatric population. PMID- 29787880 TI - Comparison of Surgical Invasiveness Between Microdiscectomy and 3 Different Endoscopic Discectomy Techniques for Lumbar Disc Herniation. AB - OBJECTIVE: Muscle injury is inevitable during surgical exposure of the spine. This study compared paraspinal muscle injury after 4 surgical techniques: microdiscectomy (MD), percutaneous endoscopic lumbar discectomy (PELD), percutaneous endoscopic interlaminar discectomy (PEID), unilateral biportal endoscopic discectomy (UBED). METHODS: Eighty patients who underwent MD, PELD, PEID, and UBED were prospectively observed. Creatine phosphokinase (CPK) and C reactive protein levels were measured on admission and postoperative days 1, 3, 5, and 7. CPK ratio was calculated as CPK on postoperative day 1/CPK on admission. Cross-sectional area of the high-intensity lesion in the paraspinal muscle was measured on magnetic resonance imaging after surgery. Operative time and hospital stay duration were also examined. Clinical outcome was evaluated using the visual analog scale for back and leg pain. RESULTS: MD group had the highest CPK levels on postoperative days 1 and 3 and CPK ratio (P < 0.01, P = 0.02, P = 0.04). Serial C-reactive protein levels were highest in MD group (P < 0.01). PELD and PEID groups had lower C-reactive protein level on postoperative day 1 than UBED group. MD group had largest cross-sectional area (P < 0.01). Cross-sectional area was larger in UBED group than in PELD and PEID groups (P < 0.01). Operative time and hospital stay duration were shortest in PELD group (P < 0.01, P < 0.01). MD group had significantly higher visual analog scale scores for back pain on postoperative days 1 and 3 than the other groups (P < 0.01, P = 0.02). CONCLUSIONS: PELD is the least invasive spinal surgical technique. PMID- 29787882 TI - Effect of the surface acid sites of tungsten trioxide for highly selective hydrogenation of cellulose to ethylene glycol. AB - This work studied a facile and template-free hydrothermal route for controlled synthesis of tungsten trioxide in the form of hexagonal nanorod (h-WO3) and monoclinic nanosheet (m-WO3). The surface morphology, crystal plane, surface bound water, and surface acid sites of the two kinds of WO3 nanocrystals were investigated systematically. They were further evaluated as catalysts for selective cellulose hydrolysis. While both of them exhibited good catalytic performance, h-WO3 was found to be more preferential for ethylene glycol (EG) generation. This catalytic performance relied on both the unique active crystal surface (1 0 0) and surface binding water (WO3-H2O) formed by h-WO3 crystals, which provided more Lewis acid sites for degrading cellulose into EG. Results showed that the highest EG yield reaches 77.5% by a combination of loading 1 wt% Ru on the h-WO3 catalyst. PMID- 29787881 TI - Long-Term Follow-Up After Radiosurgery of Papillary Tumor of Pineal Region: 2 Case Reports and Review of Literature. AB - BACKGROUND: Tumors of the pineal region are rare in adulthood, accounting for approximately 1% of intracranial neoplasms in this age range. Because of their rarity, it has proven to be difficult to establish the optimal therapy. Furthermore, microsurgical total resection in this eloquent location is associated with not low rates of morbidity. CASE DESCRIPTION: We describe 2 patients diagnosed with papillary tumors of the pineal region by stereotactic biopsy and referred for Gamma Knife radiosurgery after shunting for hydrocephalus. We report a long-term follow-up of 15 and 20 years, respectively, showing a good response to the treatment. CONCLUSIONS: After a diagnosis of papillary tumors of the pineal region, radiosurgery is an alternative treatment, with high local control and low morbidity. PMID- 29787883 TI - Modeling, experimental validation and optimization of Prosopis juliflora fuelwood pyrolysis in fixed-bed tubular reactor. AB - This work studied the optimal conditions for pyrolysis of Prosopis juliflora wood in fixed-bed tubular reactor. The optimal conditions are measured by performing pyrolysis experiment with respect to wood properties such as particle size, moisture and pyrolysis condition such as, temperatures, heating rates. Higher solid yield (36.8%) was recorded for a slower heating rate of larger particle size at lower temperatures. Further, higher liquid yield (38.3%) was observed while maintaining high heating rate and temperature. It is observed that with increase in particle size, the yield of char and gas decreases and bio-oil increases. The literature reported biomass pyrolysis kinetic model is validated for Prosopis juliflora wood. The kinetic models are able to predict the performance of fixed-bed tubular reactor in terms of pyrolysis product properties. The validated kinetic model may be used for the design of commercial fixed bed pyrolysis reactor to process Prosopis juliflora wood. PMID- 29787884 TI - The pelletization and combustion properties of torrefied Camellia shell via dry and hydrothermal torrefaction: A comparative evaluation. AB - The torrefaction performance and properties of torrefied CS (Camellia shell) bio char obtained via dry and hydrothermal torrefaction have been compared as well as pyrolysis and combustion properties. And making of torrefied pellets and their properties such as pellet density, Meyer hardness, and energy consumption are also investigated. The results showed that dry torrefied bio-char had higher energy and density at 220 degrees C and decreased significantly with temperature, while hydrothermally prepared bio-char had stable energy and mass yield with temperature. The coalification status of hydrothermally bio-char is similar to that of sub-bituminous coal. The pellet formed from dry terrified bio char via quart tube in 220 degrees C with high pellet density (1048 kg/m3) and low energy consumption (17.6 KJ/kg) in spite of low the Meyer hardness (6.8 N/mm2). As for the process kinetics, the activation energy via dry torrefection with auger showed lower activation energy 43.26 KJ/mol as well as lowest ignition temperature (290 degrees C), compared to hydrothermal torrefaction. PMID- 29787885 TI - Exposing splicing forgery based on color temperature estimation. AB - Splicing is one of the most common tampering techniques for image manipulation in many forensic cases. Normally color shift in images due to color temperature of illumination can be seen as intrinsic features relative to imaging process. In splicing forgeries, copied area and pasted target image come from different imaging process, and are likely to have different color shift. In this paper, a novel automated authentication method is presented to expose splicing manipulation and locate manipulated areas by discriminating the inconsistencies of color shift in an image. In order to minimize human interaction on detection of splicing forgeries as well as localization of manipulated areas, a forensic image is divided into blocks with grid-based strategy. After calculation on color temperature of each blocks with white-point algorithm, reference color temperature is obtained with a random restricted algorithm. Then color temperature distance between each block and reference area is calculated sequentially. At last, by comparing color temperature distance with an optimized threshold determined by OSTU algorithm. This method enables us to judge if splicing has occurred and furthermore localize manipulated area simultaneously. Experiments show that the proposed method can speed up the quantitative detection of possible splicing manipulation and localize manipulated area automatically. PMID- 29787886 TI - Monomicrobial Klebsiella pneumoniae necrotizing fasciitis: an emerging life threatening entity. AB - BACKGROUND AND AIMS: Necrotizing fasciitis (NF) although rare, is a potentially fatal infection. The majority of cases are polymicrobial, although a recent surge has been reported in monomicrobial NF caused by Klebsiella pneumoniae (KP-NF). KP NF recently accounted for an average of 16% among all pathogens, with highest mortality rate of 60%. This review discusses the important aspects of KP-NF with additional notes on the implications of multidrug resistant infections. SOURCES: The literature was searched using PubMed. Klebsiella pneumoniae isolated monomicrobially in NF cases was used as the selection criteria. CONTENT: KP-NF predominates in East Asia with the majority of cases reported from Taiwan alone. Reports from the Western hemisphere are also gradually rising. This infection has invariably presented with underlying predisposing factors occurring mostly in individuals with compromised host immunity. Diabetes, chronic liver disease, and instrumentation are important risk factors. With haematogenous spread more common, multifocal involvement via metastasis is reported. Clinical presentations are usually aggressive with rapid progression despite antimicrobial therapy. It may even present with severe sepsis. Clinicians must be aware of the differential diagnosis of such severe presentations. Emergency surgical explorations and microbiological investigations clinch the diagnosis. Outcomes are not favourable, with a high mortality rate of 40% even after appropriate interventions. Nosocomial KP-NF cases are more fulminant and multidrug resistant with even higher mortality rates (approx. 70%). IMPLICATIONS: KP-NF with its virulent course and high mortality, is an emerging life threat. Clinicians must be aware of its key features. Further comprehensive studies are needed for better insights into the spectrum of this fatal infection. PMID- 29787887 TI - Human pegivirus persistence in the human blood virome after allogeneic haematopoietic stem cell transplantation. AB - OBJECTIVES: As commensal viruses are defined by the immunological tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem cell transplantation, may shift the demarcation between innocuous viral resident and disease-causing pathogen. METHODS: We analysed by deep-sequencing the plasma virome of 40 allogeneic haematopoietic stem cell transplant (allo HSCT) patients 1 month post-transplantation. As human pegivirus (HPgV) was highly prevalent, we performed a one-year screening of 122 plasma samples by specific rRT-PCR assay. We used log rank test and the Gray test to assess association with outcomes and Mann-Whitney test and multivariable linear regression model to assess association with T-cell reconstitution. RESULTS: Polyomaviruses (PyV) (20/40 patients), anelloviruses (16/40), pegiviruses (14/40) and herpesviruses (14/40) were most frequently identified, including 10 cytomegalovirus, 3 Epstein Barr, 2 herpes simplex-1, 1 human herpesvirus (HHV)-6b and 1 HHV-7; 18 Merkel cell-PyV, 2 BK-PyV, 3 PyV-6 and 1 JC-PyV. Papillomavirus and adenovirus were identified in 11 and 2 patients, respectively. The HPgV-specific rRT-PCR screening identified 51/122 positive samples, high viral loads and persistent infections up to one year post-transplantation. Comparison between patients with or without HPgV infection at time of transplantation didn't reveal significant difference in infections, engraftment, survival, graft-versus-host disease, relapse or immune reconstitution. CONCLUSION: The blood virome after allo-HSCT includes several DNA viruses notably herpesviruses and polyomaviruses. Among RNA viruses, HPgV is highly prevalent, persisting for several months and thus may deserve special attention in further research on immune reconstitution. PMID- 29787888 TI - Understanding the microbiome of diabetic foot osteomyelitis: insights from molecular and microscopic approaches. AB - OBJECTIVES: Rigorous visual evidence on whether or not biofilms are involved in diabetic foot osteomyelitis (DFO) is lacking. We employed a suite of molecular and microscopic approaches to investigate the microbiome, and phenotypic state of microorganisms involved in DFO. METHODS: In 20 consecutive subjects with suspected DFO, we collected intraoperative bone specimens. To explore the microbial diversity present in infected bone we performed next generation DNA sequencing. We used scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with confocal microscopy to visualize and confirm the presence of biofilms. RESULTS: In 19 of 20 (95%) studied patients presenting with DFO, it was associated with an infected diabetic foot ulcer. By DNA sequencing of infected bone, Corynebacterium sp. was the most commonly identified microorganism, followed by Finegoldia sp., Staphylococcus sp., Streptococcus sp., Porphyromonas sp., and Anaerococcus sp. Six of 20 bone samples (30%) contained only one or two pathogens, while the remaining 14 (70%) had polymicrobial communities. Using a combination of SEM and PNA-FISH, we identified microbial aggregates in biofilms in 16 (80%) bone specimens and found that they were typically coccoid or rod-shaped aggregates. CONCLUSIONS: The presence of biofilms in DFO may explain why non-surgical treatment of DFO, relying on systemic antibiotic therapy, may not resolve some chronic infections caused by biofilm-producing strains. PMID- 29787889 TI - Diagnosis of bloodstream infections from positive blood cultures and directly from blood samples: recent developments in molecular approaches. AB - BACKGROUND: Bloodstream infections are a major cause of death with increasing incidence and severity. Blood cultures are still the reference standard for microbiological diagnosis, but are rather slow. Molecular methods can be used as add-on complementary assays. They can be useful to speed up microbial identification and to predict antimicrobial susceptibility, applied to direct blood samples or positive blood cultures. AIM: To review recent developments in molecular-based diagnostic platforms used for the identification of bloodstream infections, with a focus on assays performed directly on blood samples and positive blood cultures. SOURCES: Peer reviewed articles, conference abstracts, and manufacturers' websites. CONTENT: We give an update on recent developments of molecular methods in diagnosing BSIs. We first describe the currently available molecular methods to be used for positive blood cultures including: a) in situ hybridization-based methods; b) DNA-microarray-based hybridization technology; c) nucleic acid amplification-based methods; and d) combined methods. Subsequently, molecular methods applied directly to whole blood samples are discussed, including the use of nucleic acid amplification-based methods, T2 magnetic resonance-based methods, and metagenomics for diagnosing BSIs. IMPLICATIONS: Advances in molecular-based methods complementary to conventional blood culture diagnostics and antimicrobial stewardship programmes may optimize infection management by allowing rapid identification of pathogens and relevant antimicrobial resistance genes. Rapid diagnosis of the causing microorganism and relevant resistance determinants is important for early administration and modification of appropriate antimicrobial therapy. Ultimately, this may lead to improved quality and cost-effectiveness of health care, as well as reduced antimicrobial resistance selection. PMID- 29787890 TI - Invasive mould disease in haematologic patients: comparison between fusariosis and aspergillosis. AB - OBJECTIVES: To compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF). METHODS: We retrospectively reviewed the charts of 36 patients with IA and 26 with IF diagnosed between 2006 and 2017 in haematologic patients, and compared baseline characteristics, coexisting exposures, clinical manifestations, treatment, and the outcome. RESULTS: Fever was more frequent in IF (96.2% vs. 63.9%, p 0.003), whereas pneumonia (88.9% vs. 50.0%, p 0.001) and sinusitis (63.9% vs. 38.5%, p 0.048) were more frequent in IA. Skin lesions and positive blood cultures occurred exclusively in patients with IF. Among patients with pneumonia, the halo sign was more frequent in IA (62.5% vs. 23.1%, p 0.02). Serum galactomannan was positive in 88.6% of patients with IA and in 73.3% with IF (p 0.18), with no differences in the median number of positive tests and galactomannan values. Positive serum galactomannan plus lung infiltrates was the predominant clinical presentation in IA and occurred in four of 13 patients with IF and lung involvement. The 30-day survival was 77.7% in IA and 46.1% in IF (p 0.01). CONCLUSIONS: IA and IF share the same epidemiologic scenario but different clinical presentations in the majority of cases, with disease in the airways in IA, and fever, metastatic skin lesions, and positive blood cultures in IF. However, a substantial proportion of patients with IF present with a clinical picture similar to IA, with fever, lung infiltrates, and positive serum galactomannan. PMID- 29787891 TI - Development of postural control in infancy in cerebral palsy and cystic periventricular leukomalacia. AB - BACKGROUND: Development of postural problems in Cerebral Palsy (CP) is largely unknown. Postural muscle activity is organized into two levels: 1) direction specificity; 2) fine-tuning of direction-specific activity. AIM: To study development of postural control until 21 months corrected age in subgroups of infants at very high-risk (VHR) of CP: a) with and without CP at 21 months; b) with and without cystic periventricular leukomalacia (cPVL), the brain lesion with highest risk of CP. METHODS AND PROCEDURES: Longitudinal electromyography recordings of postural muscles during reaching were made in 38 VHR-infants (severe brain lesion or clear neurological signs) between 4.7 and 22.6 months (18 CP, of which 8 with cPVL). Developmental trajectories were calculated using linear mixed effect models. OUTCOMES AND RESULTS: VHR-infants with and without CP showed virtually similar postural development throughout infancy. The subgroup of VHR-infants with cPVL improved performance in direction-specificity with increasing age, while they performed throughout infancy worse in fine-tuning of postural adjustments than infants without cPVL. CONCLUSIONS AND IMPLICATIONS: VHR infants with and without CP have a similar postural development that differs from published trajectories of typically developing infants. Infants with cPVL present from early age onwards dysfunctions in fine-tuning of postural adjustments; they focus on direction-specificity. PMID- 29787892 TI - The role of bisphosphonates or denosumab in light of the availability of new therapies for prostate cancer. AB - Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments. These compounds have benefits in terms of overall survival based on the results of pivotal phase 3 studies. The bisphosphonate zoledronic acid and the RANK ligand inhibitor denosumab are indicated for the prevention of SREs in men with metastatic CRPC but studies of these compounds have not demonstrated a survival benefit. The important question of the role of bisphosphonates or denosumab in combination with these new agents has thus materialised. Current and emerging evidence from clinical studies of abiraterone acetate, enzalutamide and radium-223, suggest that addition of bisphosphonates or denosumab to these new therapies may provide further clinical benefits for patients with prostate cancer and bone metastases. This evidence may help to shape clinical practice but are based largely on post hoc analyses of clinical trial data. It is therefore apparent that further data are required from both clinical studies and real-world settings to enable physicians to understand the efficacy and safety of combination therapy with the new agents plus bisphosphonates or denosumab. PMID- 29787893 TI - Effect of glycerol on the physical and mechanical properties of thin gellan gum films for oral drug delivery. AB - In this work, deacylated gellan gum and the plasticizer glycerol were used as primary components for the preparation of thin films intended for the oral delivery of therapeutic molecules. The samples were prepared by a solvent casting method and characterized for their thickness, tensile properties, swelling ability, mucoadhesion capacity and uniform drug distribution. The amount of glycerol was varied from 20% to 75% w/w in order to obtain films with tunable mechanical properties and high drug loading efficiency. The addition of glycerol was able to positively influence the mechanical characteristics of gellan gum thin film overcoming the brittleness caused by the rigid interconnection among the polymeric chains. Plasticized gellan gum films containing 50% w/w of glycerol showed optimal mechanical resistance and mucoadhesion capacity, which were adversely affected by the inclusion of higher concentrations of glycerol. On the contrary, only high amounts of the plasticizer (>=70% w/w) enabled a homogeneous distribution of the model drug fluconazole within the polymeric matrix. Overall, these results indicate that gellan gum-based thin films can be potentially used for buccal drug delivery upon precise selection of the appropriate concentration of glycerol used as a plasticizer. PMID- 29787894 TI - 3D printing of drug-loaded gyroid lattices using selective laser sintering. AB - Three-dimensional printing (3DP) is gaining momentum in the field of pharmaceuticals, offering innovative opportunities for medicine manufacture. Selective laser sintering (SLS) is a novel, high resolution and single-step printing technology that we have recently introduced to the pharmaceutical sciences. The aim of this work was to use SLS 3DP to fabricate printlets (3D printed tablets) with cylindrical, gyroid lattice and bi-layer structures having customisable release characteristics. Paracetamol-loaded constructs from four different pharmaceutical grade polymers including polyethylene oxide, Eudragit (L100-55 and RL) and ethyl cellulose, were created using SLS 3DP. The novel gyroid lattice structure was able to modulate the drug release from all four polymers. This work is the first to demonstrate the feasibility of using SLS to achieve customised drug release properties of several polymers, in a swift, cost effective manner, avoiding the need to alter the formulation composition. By creating these constructs, it is therefore possible to modify drug release, which in practice, could enable the tailoring of drug performance to the patient simply by changing the 3D design. PMID- 29787895 TI - Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. AB - Poly (amidoamine) (PAMAM) dendrimers are well-defined, highly branched macromolecules with numerous active amine groups on the surface. Because of their unique properties, PAMAM dendrimers have steadily grown in popularity in drug delivery, gene therapy, medical imaging and diagnostic application. This review focuses on the recent developments on the application in PAMAM dendrimers as effective carriers for drug and gene (pDNA, siRNA) delivery in cancer therapy, including: a) PAMAM for anticancer drug delivery; b) PAMAM and gene therapy; c) PAMAM used in overcoming tumor multidrug resistance; d) PAMAM used for hybrid nanoparticles; and e) PAMAM linked or loaded in other nanoparticles. PMID- 29787896 TI - Comparison of high pressure homogenization and stirred bead milling for the production of nano-crystalline suspensions. AB - Currently, the two technologies primarily used for the manufacturing of nano crystalline suspensions using top down process (i.e. wet milling) are high pressure homogenization (HPH) and stirred bead milling (SBM). These two technologies are based upon different mechanisms, i.e., cavitation forces for HPH and shear forces for stirred bead milling. In this article, the HPH and SBM technologies are compared in terms of the impact of the suspension composition the process parameters and the technological configuration on milling performances and physical quality of the suspensions produced. The data suggested that both HPH and SBM are suitable for producing nano-crystalline suspensions, although SBM appeared more efficient than HPH, since the limit of milling (d50) for SBM was found to be lower than that obtained with HPH (100 nm vs 200 nm). For both these technologies, regardless of the process parameters used for milling and the scale of manufacturing, the relationship of d90 versus d50 could be described by a unique master curve (technology signature of milling pathway) outlining that the HPH leads to more uniform particle size distribution as compared to SBM. PMID- 29787897 TI - Structural and genetic relatedness of the O-antigens of Escherichia coli O50 and O2. AB - An O-specific polysaccharide (O-antigen) was isolated by mild acid degradation of the lipopolysaccharide of Escherichia coli O50 followed by gel chromatography on Sephadex G-50. The following structure of the tetrasaccharide repeat was established by sugar analysis and 1D and 2D 1H and 13C NMR spectroscopy: ->3) alpha-l-Rhap-(1 -> 2)-alpha-l-Rhap-(1 -> 3)-beta-l-Rhap-(1 -> 4)-beta-d-GlcpNAc (1-> The linear O50 polysaccharide has the same structure as the main chain of the branched O polysaccharide of E. coli O2 studied earlier [Jansson et al., Carbohydr. Res. 161 (1987) 273-279], which differs in the presence of a side chain alpha-d-Fucp3NAc residue. In spite of the difference between the O polysaccharides, the corresponding genes in the O2- and O50-antigen gene cluster are 99-100% identical. The genetic basis for the lack of d-Fucp3NAc from the O50 polysaccharide is evidently a point mutation in the aminotransferase gene fdtB of the d-Fucp3NAc synthesis pathway resulting in a single amino acid change from histidine in O2 to arginine in O50. PMID- 29787898 TI - Long-term effects of air pollution on ankle-brachial index. AB - BACKGROUND: Ankle-brachial index (ABI) has been linked to the risk of cardiovascular events. However, the association between long-term exposure to air pollution and abnormal ABI has not been fully investigated. METHODS: This cross sectional study involved 4544 participants from the KORA Study (2004-2008) in the region of Augsburg, Germany. Participants' residential annual mean concentrations of particulate matter (PM) and nitrogen dioxide (NO2) were predicted with land use regression models, and the traffic information was collected from geographic information systems. We applied multinomial logistic regression models to assess the effects of air pollution on the prevalence of low and high ABI, and quantile regression models to explore the non-monotonic relationship between air pollution and ABI. We also examined effect modification by individual characteristics. RESULTS: Long-term exposure to PM with an aerodynamic diameter <= 10 MUm (PM10) and <= 2.5 MUm (PM2.5) was significantly associated with a higher prevalence of low ABI, with the respective odds ratios (ORs) of 1.82 (95%CI: 1.11-2.97) and 1.59 (95%CI: 1.01-2.51) for a 5th to 95th percentile increment in pollutants. Positive associations with the prevalence of high ABI were observed for PM (e.g., PM10: OR = 1.63, 95%CI: 1.07-2.50) and NO2 (OR = 1.84, 95%CI: 1.15-2.94). Quantile regression analyses revealed similar non-monotonic results. The effects of air pollution on having abnormal ABI were stronger in physically inactive, hypertensive, or non-diabetic participants. CONCLUSIONS: Long-term exposure to PM and NO2 was associated with a higher prevalence of both low and high ABI, indicating the adverse effects of air pollution on atherosclerosis and arterial stiffness in the lower extremities. PMID- 29787899 TI - Dermal contact with furniture fabrics is a significant pathway of human exposure to brominated flame retardants. AB - Despite extensive application in consumer products and concerns over their adverse health effects, how external exposure to brominated flame retardants (BFRs) contributes to their human body burdens is not yet fully understood. While recent studies focused on inadvertent indoor dust ingestion and diet as potential major pathways of exposure, dermal uptake has been largely overlooked. We provide the first experimentally-based assessment of dermal uptake of BFRs via contact with indoor dust and flame-retarded furniture fabrics. Results reveal substantial uptake from furniture fabrics (e.g. 8.1 ng pentaBDE/kg bw/day for adults in summer), exceeding the overall adult intake of pentaBDE estimated previously via other exposure pathways. For HBCDs, despite the low absorption fraction (<2.5%) from the studied fabrics, the estimated dermal uptake of UK adults and toddlers (101 and 76.9 ng/kg bw/day) exceed the reported average daily intakes of 7.9 and 43.0 ng/kg bw/day for these UK age groups. Conversely, uptake from dust was low (0.05 and 0.19 ng pentaBDE/kg bw/day for adults and toddlers, respectively), indicating previous pharmacokinetic approaches may have overestimated the significance of this route. Future exposure and risk assessment studies should consider dermal contact with treated products as a significant pathway of human exposure to BFRs and related chemicals. PMID- 29787900 TI - Associations between prenatal and childhood PBDE exposure and early adolescent visual, verbal and working memory. AB - BACKGROUND: Prenatal and childhood exposure to polybrominated diphenyl ether (PBDE) flame retardants has been inversely associated with cognitive performance, however, few studies have measured PBDE concentrations in samples collected during both prenatal and postnatal periods. METHODS: We examined prenatal (cord) and childhood (ages 2, 3, 5, 7 and 9 years) plasma PBDE concentrations in relation to memory outcomes assessed between the ages of 9 and 14 years. The study sample includes a subset (n = 212) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used multivariable linear regression to examine associations between continuous log10-transformed PBDE concentrations and performance on tests of visual, verbal and working memory in age-stratified models. We additionally used latent class growth analysis to estimate trajectories of exposure across early life, which we analyzed as a categorical variable in relation to memory outcomes. We examined interactions between PBDE exposure and sex using cross-product terms. RESULTS: Associations between prenatal exposure and working memory significantly varied by sex (p-interaction = 0.02), with inverse relations observed only among girls (i.e. betaBDE-47 = -7.55, 95% CI: -13.84, -1.24). Children with sustained high concentrations of BDEs-47, 99 or 100 across childhood scored approximately 5-8 standard score points lower on tests of visual memory. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were not statistically significant. CONCLUSIONS: Exposure to PBDEs during both prenatal and postnatal periods may disrupt memory domains in early adolescence. These findings contribute to a substantial body of evidence supporting the developmental neurotoxicity of PBDEs and underscore the need to reduce exposure among pregnant women and children. PMID- 29787901 TI - Profiling of phenolic compounds and antioxidant properties of European varieties and cultivars of Vicia faba L. pods. AB - Vicia faba L. pods are a by-product generated from the industrial processing of beans for human and animal consumption. As phenolic compounds may play important roles in health, the present work envisaged the phenolic characterization of seven European varieties and cultivars of V. faba (major and minor) pods and the assessment of their antioxidant activity. The V. faba methanolic extracts were characterized by HPLC-DAD-MS/MS for identification of polyphenolic compounds. The total phenolic content and antioxidant capacity of the extracts were evaluated by colorimetric methods (Folin-Ciocalteu, DPPH scavenging capacity assay, and FRAP assay). Main compounds identified by HPLC-DAD-MS/MS were derivatives of caffeic acid, coumaric acid and kaempferol. The broad bean Jogeva variety presented the highest content of free and esterified phenolics (26.3 and 26.7 mg 100 g-1 dry weight, respectively), followed by the horse bean varieties Bauska and Lielplatones. These results were corroborated by the analysis of total phenolic content, DPPH scavenging capacity and FRAP. This study confirmed the rich phenolic content of V. faba pods suggesting to be an interesting novel source for animal nutrition, promoting product quality and consumers' health. PMID- 29787902 TI - Mineralogy and morphology of sand: Key parameters in the durability for its use in artificial beach nourishment. AB - Sand is the third most consumed material in the world, although it is a very scarce material. An exhaustive knowledge of sand and its behaviour against the waves is important for selecting the most suitable material to avoid shoreline erosion. To this end, a pattern of behaviour against accelerated wear test has been sought for 26 sand samples with different characteristics and origins (natural, dredged and quarried), with a focus on their mineralogy as well as a comparison of beach evolution carried out by other authors. Several techniques have been applied for characterization: granulometry, calcimetry, XRD and SEM. The results show that the different degrees of sand grain wear are not only due to their size and mineralogy, but also to the morphology of the particles. PMID- 29787903 TI - Flood risk (d)evolution: Disentangling key drivers of flood risk change with a retro-model experiment. AB - Flood risks are dynamically changing over time. Over decades and centuries, the main drivers for flood risk change are influenced either by perturbations or slow alterations in the natural environment or, more importantly, by socio-economic development and human interventions. However, changes in the natural and human environment are intertwined. Thus, the analysis of the main drivers for flood risk changes requires a disentangling of the individual risk components. Here, we present a method for isolating the individual effects of selected drivers of change and selected flood risk management options based on a model experiment. In contrast to purely synthetic model experiments, we built our analyses upon a retro-model consisting of several spatio-temporal stages of river morphology and settlement structure. The main advantage of this approach is that the overall long-term dynamics are known and do not have to be assumed. We used this model setup to analyse the temporal evolution of the flood risk, for an ex-post evaluation of the key drivers of change, and for analysing possible alternative pathways for flood risk evolution under different governance settings. We showed that in the study region the construction of lateral levees and the consecutive river incision are the main drivers for decreasing flood risks over the last century. A rebound effect in flood risk can be observed following an increase in settlements since the 1960s. This effect is not as relevant as the river engineering measures, but it will become increasingly relevant in the future with continued socio-economic growth. The presented approach could provide a methodological framework for studying pathways for future flood risk evolvement and for the formulation of narratives for adapting governmental flood risk strategies to the spatio-temporal dynamics in the built environment. PMID- 29787904 TI - Effective and sensitive determination of eleven disinfection byproducts in drinking water by DLLME and GC-MS. AB - The aim of this study was to optimize the dispersive liquid-liquid microextraction (DLLME) parameters for simultaneous analysis through DLLME-gas chromatography-mass spectrometry (GC-MS) of six iodo-trihalomethanes, four haloacetonitriles, and one halonitromethane, which are residual disinfection products found in drinking water. Eleven disinfection by-product (DBPs) remaining in aqueous samples were extracted and concentrated using a simple, rapid, and environmentally friendly DLLME method, and then analyzed simultaneously by GC-MS. The optimized DLLME parameters were a sample volume of 5 mL, 100 MUL of dichloromethane as the extraction solvent, 1 mL of methanol as the dispersion solvent, an extraction time of 60 s, and 1.5 g of sodium chloride for the salting out effect. The enrichment factor values obtained using the established DLLME-GC MS method were 19.8-141.5, and the limit of detection and limit of quantification were 0.22-1.19 MUg/L and 0.75-3.98 MUg/L, respectively. The calibration curves had correlation coefficients (r2) of 0.9958-0.9992 in the concentration range of 0.5-40 MUg/L, and they exhibited good linearity in quantitative analysis. This new method could be useful for analyzing eleven DBPs that remain in drinking water. PMID- 29787905 TI - Heavy metal pollution caused by small-scale metal ore mining activities: A case study from a polymetallic mine in South China. AB - Although metal ore mining activities are well known as an important source of heavy metals, soil pollution caused by small-scale mining activities has long been overlooked. This study investigated the pollution of surface soils in an area surrounding a recently abandoned small-scale polymetallic mining district in Guangdong province of south China. A total of 13 tailing samples, 145 surface soil samples, and 29 water samples were collected, and the concentrations of major heavy metals, including Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Pb, and Se, were determined. The results show that the tailings contained high levels of heavy metals, with Cu, Zn, As, Cd, and Pb occurring in the ranges of 739-4.15 * 103, 1.81 * 103-5.00 * 103, 118-1.26 * 103, 8.14-57.7, and 1.23 * 103-6.99 * 103 mg/kg, respectively. Heavy metals also occurred at high concentrations in the mine drainages (15.4-17.9 mg/L for Cu, 21.1-29.3 mg/L for Zn, 0.553-0.770 mg/L for Cd, and 1.17-2.57 mg/L for Pb), particularly those with pH below 3. The mean contents of Cu, Zn, As, Cd, and Pb in the surface soils of local farmlands were up to 7 times higher than the corresponding background values, and results of multivariate statistical analysis clearly indicate that Cu, Zn, Cd, and Pb were largely contributed by the mining activities. The surface soils from farmlands surrounding the mining district were moderately to seriously polluted, while the potential ecological risk of heavy metal pollution was extremely high. It was estimated that the input fluxes from the mining district to the surrounding farmlands were approximately 17.1, 59.2, 0.311, and 93.8 kg/ha/yr for Cu, Zn, Cd, and Pb, respectively, which probably occurred through transport of fine tailings by wind and runoff, and mine drainage as well. These findings indicate the significant need for proper containment of the mine tailings at small-scale metal ore mines. PMID- 29787906 TI - The use of combined treatments for reducing parabens in surface waters: Ion exchange resin and nanofiltration. AB - In this study, the removal of parabens from waters, using a combined treatment of magnetic ion exchange resins and subsequent filtration through nanofiltration membranes, was investigated. The selected parabens were methylparaben, ethylparaben, propylparaben and butylparaben. Two different magnetic anionic exchanger resins, MIEX(r) DOC and MIEX(r) GOLD, and two nanofiltration membranes (NF), NF-90 and DESAL-HL, were tested. The study was carried out using mono and multicomponent systems, using deionized water and natural waters sampled from two different rivers. In this way, competitive and matrix effects could be evaluated. The results showed, that with the combined treatments, higher elimination rates were obtained. The best removal efficiencies were obtained when the DOC resin was combined with both NF-90 and DESAL-HL membranes. Thus, butylparaben and propylparaben reached removal yields around 100% with both membranes, whereas the corresponding values for methylparaben were 91%, when the NF-90 membrane was employed, or 92% when DESAL-HL membrane was utilized. The elimination rates of ethylparaben with the same treatments were 96% with the NF-90 and 97% when the DESAL-HL membrane was combined with the DOC resin. The elimination percentages were higher as the paraben alkyl chain length increased. In addition, no competitiveness or matrix effects were detected. When the MIEX(r) GOLD resin was used for pre-treatment, membrane fouling worsened which indicated that resin selection needs to be carefully considered to achieve the best results. PMID- 29787907 TI - Response of net primary production to land use and land cover change in mainland China since the late 1980s. AB - Land use and land cover patterns in mainland China have substantially changed in the recent decades under the economic reform policies of the government. The terrestrial carbon cycle, particularly the net primary productivity (NPP), has been substantially changed on both local and national scales. With the growing concern over the effects of the terrestrial carbon cycle on global climate changes, the impacts of land use and cover change (LUCC) on NPP need to be understood. In this study, variations in NPP caused by LUCC (e.g., urbanization and conversion of other land use to forest and grassland) in mainland China from the late 1980s to 2015 were evaluated based on land cover datasets and NPPs simulated from the Carnegie-Ames-Stanford Approach model. The results indicate that the national total losses in NPP attributed to urbanization reached 1.695 TgC between the late 1980s and 2015. A large proportion (63.02%) of the total losses was due to the transformation from cropland to urban land. Urban expansion decreased the monthly and total NPPs over southern China, which includes the South China Region, Southwest China Region, and the middle and lower regions of the Yangtze River. However, the total NPP increased in the majority of urbanized areas in Northern China, including the Huang-Huai-Hai Region, Inner Mongolia Region (MGR), Gan-Xin Region (GXR), and Northeast China Region; monthly NPP in GXR and MGR increased throughout the year. By contrast, the conversion to grassland or forestland increased the monthly and total NPPs of Northern China, suggesting that returning to forestland and grassland could increase the carbon sequestration capacity of terrestrial ecosystems in mainland China. Among the sub regions, the Loess Plateau Region contributed the largest increase in NPP, which was prompted by the conversion to grassland and forestland. PMID- 29787908 TI - Impact of fouling on the decline of aeration efficiency under different operational conditions at WRRFs. AB - Biofilm formation influences the most energy-demanding process in the waste water treatment cycle. Biofilm growth on the surface of wastewater aeration diffusers in water resource recovery facilities (WRRFs) can increase the energy requirements up to 50% in less than 2 years. The impact of biofilms in aeration diffusers was quantified and assessed for first time using molecular tools (i.e., Energy-dispersive X-ray, Ra and RMS and Pyrosequencing) and state-of-the-art techniques (i.e., EPS quantification, Hydrophobicity and DNA quantification). To provide a better understanding and quantitative connections between biological activity and aeration energy efficiency, two replicates of the most common diffusers were installed and tested in two different operational conditions (higher and lower organic loading rate processes) during 15 months. Different scenarios and conditions provided for first time comprehensive understanding of the major factors contributing to diffuser fouling. The array of analysis suggested that higher loading conditions can promote specialized microbial populations to halve aeration efficiency parameters (i.e., alphaF) in comparison to lower loading conditions. Biofilms adapted to certain operational conditions can trigger changes in diffuser membrane properties (i.e., biological enhanced roughness and hydrophobicity) and enhance EPS growth rates. Improved understanding of the effects of scaling, biofouling, aging and microbial population shifts on the decrease in aeration efficiency is provided. PMID- 29787909 TI - A modified method of high molecular weight adsorbable organic chlorine measurement in saline water: Dialysis pretreatment. AB - Adsorbable organic halogen is a mean to quantify total organic halogen, which is an important toxicity indicator in disinfection byproduct studies. However, quantification of low concentrations of adsorbable organic chlorine (AOCl) formation in seawater chlorination using the USEPA Method 9020B was found inaccurate due to the presence of high concentrations of chloride. In this study, a dialysis-based pretreatment technique was proposed, optimized and adopted to eliminate the interference of chloride in quantifying low concentrations of AOCl in seawater. A volumetric ratio of dialysis samples to continuous-flow deionized water at 1:1200 was found sufficient to remove over 99% of chloride. As a result, chloride to AOCl ratios can be reduced to less than 20,000, and the interference from chloride can thus be eliminated. The detainment of AOCl by the dialysis pretreatment depends on the molecular weight cutoff of the cellulose seamless dialysis membrane currently used, which was determined to be around 320 to 500 Da. The dialysis pretreatment can be used to measure AOCl concentrations in chlorinated seawater samples at pH 6.5 to 10. PMID- 29787910 TI - Temporal trends and transport of perfluoroalkyl substances (PFASs) in a subtropical estuary: Jiulong River Estuary, Fujian, China. AB - The seasonal variations and spatial distributions of fifteen perfluoroalkyl substances (PFASs) were investigated in the water of the subtropical Jiulong River Estuary (JRE) in Fujian, China. The concentrations and composition profiles of PFASs showed significant seasonal variations. ?PFASs concentrations ranged from 4.8 to 37.6 ng L-1, 12.2 to 110 ng L-1 and 3.3 to 43.0 ng L-1 in the dry, medium and wet seasons, respectively. Perfluorooctane sulfonate (PFOS) was found to be the most abundant PFAS in the dry season, with a composition of 33% +/- 5%, Perfluorohexanoic acid PFHxA (47% +/- 13%) and perfluoropentanoic acid (PFPeA) (52% +/- 15%) were the dominant compounds in the medium and wet seasons, respectively. Seasonal and spatial distributions of ?PFASs were different in the upstream and downstream sections. High concentration of PFHxA occurred in the medium season, and showed a linear decreasing trend from upstream to downstream. The majority of other PFASs did not show clear seasonal variation. Composition profiles indicated that the JRE was mainly contaminated by short-chain perfluoroalkyl carboxylic acids (PFCAs), shipbuilding industry, multiple wastewater and river runoff were identified as major potential sources. PMID- 29787911 TI - Morphology, morphogenesis, and phylogeny of an Anteholosticha intermedia (Ciliophora, Urostylida) population from the United States. AB - A distinct population of Anteholosticha intermedia was isolated from soil in the Great Smoky Mountains of North Carolina, USA, and its morphology, morphogenesis and molecular phylogeny investigated by microscopic observations of live and protargol-prepared specimens and analyses of the sequence of small subunit (SSU) rDNA. Our population closely resembles the populations from Austria and Korea. Members of the genus Anteholosticha have been regarded as ontogenetically diverse, which is confirmed by the present work. The most noteworthy ontogenetic feature of the American population of A. intermedia is that the oral primordium in the proter appears apokinetally at the posterior end of the undulating membranes anlage at the beginning of division and then dedifferentiates midway through morphogenesis. Molecular phylogenetic analyses demonstrate, with high support, that the American population of A. intermedia is clearly distinct from congeners and branches as part of a sister lineage to the Bakuella-Urostyla clade that belongs to the major clade comprising the order Urostylida. PMID- 29787912 TI - High-fat diet-induced lipidome perturbations in the cortex, hippocampus, hypothalamus, and olfactory bulb of mice. AB - Given their important role in neuronal function, there has been an increasing focus on altered lipid levels in brain disorders. The effect of a high-fat (HF) diet on the lipid profiles of the cortex, hippocampus, hypothalamus, and olfactory bulb of the mouse brain was investigated using nanoflow ultrahigh pressure liquid chromatography-electrospray ionization-tandem mass spectrometry in the current study. For 8 weeks, two groups of 5-week-old mice were fed either an HF or normal diet (6 mice from each group analyzed as the F and N groups, respectively). The remaining mice in both groups then received a 4-week normal diet. Each group was then subdivided into two groups for another 4-week HF or normal diet. Quantitative analysis of 270 of the 359 lipids identified from brain tissue revealed that an HF diet significantly affected the brain lipidome in all brain regions that were analyzed. The HF diet significantly increased diacylglycerols, which play a role in insulin resistance in all regions that were analyzed. Although the HF diet increased most lipid species, the majority of phosphatidylserine species were decreased, while lysophosphatidylserine species, with the same acyl chain, were substantially increased. This result can be attributed to increased oxidative stress due to the HF diet. Further, weight cycling (yo-yo effect) was found more critical for the perturbation of brain lipid profiles than weight gain without a preliminary experience of an HF diet. The present study reveals systematic alterations in brain lipid levels upon HF diet analyzed either by lipid class and molecular levels. PMID- 29787913 TI - Modulating the degree of fucosylation of fucosylated chondroitin sulfate enhances heparin cofactor II-dependent thrombin inhibition. AB - Fucosylated chondroitin sulfate (FCS), an unusual glycosaminoglycan with fucose side chains, is a promising anticoagulant agent. To assess the effect of its structure on anticoagulant activity, its derivatives with various degrees of fucosylation (DF), molecular weights (Mw) and sulfation patterns were prepared and characterized. Biological tests showed that their APTT (activated partial thromboplastin time) prolonging activity and intrinsic factor Xase complex (factor IXa-VIIIa-Ca2+-PL complex) inhibitory activity were both reduced in FCS derivatives with lower Mw and DF. However, FCSs with DF at least 16% resulted in greater heparin cofactor II (HCII)-dependent thrombin inhibitory activity in response to decreasing DF, and these activities did not depend on Mw (Mw > 5.2 kDa). Solution competition binding assay further suggested that modulating the DF of FCS derivatives might enhance inhibition of thrombin by activating HCII. These findings imply that FCS derivatives with suitable chain length and DF value may be novel anticoagulants by activating HCII. PMID- 29787914 TI - Free radical rearrangement synthesis and microbiological evaluation of novel 2 sulfoether-4-quinolone scaffolds as potential antibacterial agents. AB - To develop novel antibacterial agents, 2-sulfoether-4-quinolone scaffolds were synthesized by a free radical process and evaluated for their antibacterial abilities. Excellent activities against Gram-positive bacteria were observed, among which compounds 3m, 3n, 3p and 3t possessed the lowest MICs against both S. aureus and B. cereus (0.8 MUM and 1.61 MUM, respectively). The structure-activity relationship (SAR) showed that: (i) the antibacterial activity was related to the substituent, such as 2-SCH3 = 2-SCH2CH3 > 2-S(=O)CH3 > 2-OH, 8-Br > 7-Br > 6-Br; (ii) -CF3 increased the antibacterial activity; (iii) the di-substituted group performed the better activity. The DNA supercoiling inhibitory analysis confirmed their fluoroquinolone characters. The docking showed that compound 3n was nicely bound into the DNA-gryase complex via extensive interactions, including conventional hydrogen bonds, halogen bonds and hydrophobic interactions. The microscopy analysis of compound 3n against S. aureus exhibited the damages on the cell wall construction, which may facilitate the penetration into Gram-positive bacteria. PMID- 29787915 TI - Binding behavior of trelagliptin and human serum albumin: Molecular docking, dynamical simulation, and multi-spectroscopy. AB - This study aims to investigate the interaction mechanism of a hypoglycemic agent, trelagliptin (TLP), and human serum albumin (HSA) through computer simulation and assisted spectroscopy methods. Computer simulation including molecular docking and molecular dynamics analysis was conducted under physiological conditions. Molecular docking results indicate that TLP bound to HSA at site I, and the binding behavior was mainly governed by hydrophobic force. Competitive experiments further verified the theoretical conclusion from molecular docking. Molecular dynamics simulation revealed that TLP indeed stably bound to site I of HSA in the hydrophobic subdomain IIA. Moreover, TLP presented a certain effect on the structural compactness of HSA. In molecular dynamics simulation, hydrogen bonds appeared, which suggested the reliability and stability of the combination. The binding energy of the stable phase is around -250 kJ/mol. Fluorescence quenching studies and time-resolved fluorescence analysis indicated that the evident fluorescence quenching phenomenon of HSA could be due to TLP binding initiated by static quenching mechanism. The binding constants (Ka) of the complex were found to be around 104 via fluorescence data, and the calculated thermodynamic parameters indicated that hydrophobic force played major role in the binding of TLP to HSA. Synchronous fluorescence and three-dimensional fluorescence results demonstrated that TLP slightly disturbed the microenvironment of amino residues. Circular dichroism spectra showed that TLP affected the secondary structure of HSA. The theoretical and experimental results showed excellent agreement. PMID- 29787916 TI - Synthesis and photophysical characterization of isoindigo building blocks as molecular acceptors for organic photovoltaics. AB - Five isoindigo-based donor-acceptor-donor (D-A-D) type small molecules have been synthesized in order to investigate their intramolecular charge transfer characteristics. UV-vis absorption of these dyes exhibits a wide absorption band ranging from 300 to 650 nm with two distinct bands, giving the narrow bandgaps between 1.72 and 1.85 eV. Taking into account their HOMO-LUMO energy levels and bandgaps, isoindigo dyes have been used in the active layer of organic solar cell (OSC) devices. When these small molecule semiconductors were used as acceptors with the donor poly(3-hexylthiophene-2,5-diyl (P3HT) polymer in the inverted OSC devices, the highest power conversion efficiency (PCE) was obtained as 0.10% for pyrene-substituted isoindigo derivative. PMID- 29787917 TI - A2B corroles: Fluorescence signaling systems for sensing fluoride ions. AB - Four free base corroles, 1-4, A2B, (where A = nitrophenyl, and B = pentafluorophenyl, 2, 6-difluoro, 3, 4, 5-trifluoro and 4-carboxymethylphenyl group) have been synthesized, characterized and demonstrated as excellent chemosensor for the detection of fluoride ions selectively in toluene solution. The reported corroles shows highest quantum yield in free base form of porphyrinoid systems so far. All these corrole, 1-4, have the excellent ability to sense fluoride ion. Cumulative effect of static and dynamic factors is responsible for the quenching of fluorescence which indicates the detection of fluoride ion in solution. PMID- 29787918 TI - Management of adsorbent content in waste motor oil regeneration by spectrophotometrical study and effective acidification in production of nano porous clay. AB - In the present work the application of novel technique was highlighted for reduction of adsorbent content in recovery process of waste motor oil by effective acidification. The effects of acidification factors such as acid proportions, adsorbent dose, powder/acid ratio and residence time were analyzed on removal of contaminates from waste oil. Acetic, hydrochloric and sulfuric acids were mixed according to the statistical mixture design algorithm to prepare acidification agents. The dry original clay was submitted into the prepared acidic solutions. The designed instrumental setup allowed the preparation of nano porous powders where the controlled factors were residence time. The distillation of waste oil was carried out in the industrial scale. The significance of independent variables and their interactions were tested by blending the obtained powders with distillated oil and then the adsorption was evaluated, spectrophotometrically. The experimental results revealed the region in which the optimum regeneration of waste oil is obtainable. In order to well understand the role of nano-structured material on regeneration, the adsorbents were characterized through X-ray diffraction, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area measurement and scanning electron microscopy. The employment of acetic acid in combination with sulfuric acid plays an effective role in development porous structure and improvement of contaminant adsorption. The powder produced in optimum condition contains nano-pores with diameter about 11 nm. The employment of this technique provides a potential for reduction of adsorbent content, 33.3 wt%. Finally, it was demonstrated that the efficiency of prepared adsorbent supports further development for commercial application purpose. PMID- 29787919 TI - Optimal use of novel agents in chronic lymphocytic leukemia. AB - Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse. The outcomes differ depending on the underlying clonal architecture, raising the concept that personalized approaches based on clinical evaluation of each patient's clonal architecture might optimize outcomes while minimizing toxicity and cost. PMID- 29787920 TI - Identification and characterization of chemosensory genes in the antennal transcriptome of Spodoptera exigua. AB - Chemical senses are crucial for insect behaviors such as host preference, mate choice and oviposition site selection. Various protein families are involved in these processes, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), chemosensory proteins (CSPs), odorant binding proteins (OBPs) and sensory neuron membrane proteins (SNMPs). To better understand the olfactory mechanism in Spodoptera exigua, we conducted transcriptome analysis of adult antennae and identified a total of 157 candidate chemosensory genes encoding 51 ORs, 20 IRs, 7 GRs, 32 CSPs, 45 OBPs and 2 SNMPs. Quantitative real time PCR (qPCR) analysis of the tissue- and sex-specific expression profiles of ORs, GRs and IRs revealed that these genes could be detected in at least one tissue tested. SexiOR6, 11, 13 and 16, which were predicted to be pheromone receptors based on phylogenetic analysis, exhibited male-specific antennae expression. SexiOR18, 26, 28, 30, 34, 39, and 40 exhibited female-biased expression. SexiGR1, SexiGR2 and SexiGR3, are predicted carbon dioxide receptors, and the former was expressed specifically in antennae, and the latter two were expressed both in antennae and labial palps. SexiIRs had diverse expression profiles. SexiIR8a and SexiIR25a were quite conserved and expressed at high levels. This work will greatly facilitate the understanding of olfactory system in S. exigua and provides valuable information for further functional studies of the chemoreception mechanism in Lepidopteran moths. PMID- 29787921 TI - Diurnal rhythm and salivary electrolyte. PMID- 29787922 TI - The association of panic and hyperventilation with psychogenic non-epileptic seizures: A systematic review and meta-analysis. AB - INTRODUCTION: Psychogenic Non-Epileptic Seizures (PNES) are events that appear epileptic but are instead thought to have a psychological origin. Increased rates of several psychiatric disorders have been reported in PNES, including anxiety and panic disorders. Some theories suggest panic and/or hyperventilation have aetiological roles in PNES, though these remain unproven. METHODS: We conducted a systematic review of associations of panic and hyperventilation with PNES using Ovid Medline and PubMed, and a meta-analysis where appropriate. RESULTS: We found eighteen studies reporting rates of panic in PNES and eight studies reporting hyperventilation. The reported rate of panic attacks in PNES ranged from 17% to 83%, with physical symptoms more commonly reported, and affective symptoms less so. 'Dizziness or light-headedness' was found to be more prevalent than 'fear of dying' by random-effects meta-analysis (68% vs. 23%). A proportion meta-analysis found a weighted occurrence of 20% of panic disorder in PNES. A pooled meta analytic rate of PNES events following voluntary hyperventilation induction was 30%, while the clinically observed rates of peri-ictal hyperventilation in PNES without induction varied from 15 to 46%. CONCLUSIONS: Previous studies have reported moderate rates of association of panic in PNES, though the proportions varied considerably across the literature, with physical symptoms more commonly reported than affective. Hyperventilation is an effective inducer of PNES events in a minority, and can be observed occurring in a minority of patients without induction. These results support an important, albeit not essential, role for panic and hyperventilation in the pathogenesis of PNES events. PMID- 29787923 TI - Epileptic spasms: Evidence for oral corticosteroids and implications for low and middle income countries. AB - Implementation of international guidelines for the treatment of epileptic spasms, is challenging when access to adrenocorticotrophic hormone (ACTH) and vigabatrin is restricted, especially in Low and Middle Income Countries (LMIC). Oral corticosteroids are alternative interventions but evidence for the optimal agent, dose, duration, efficacy and long-term effects is lacking. A systematic review of the literature was performed to assess the quality of evidence of prednisone and prednisolone (oral corticosteroids) for the management of epileptic spasms. There is level C recommendation based on class III evidence to support the efficacy of oral corticosteroids for the acute clinical control of epileptic spasms and EEG resolution. Efficacy of oral corticosteroids in comparison to the internationally recommended intervention of ACTH has class IV evidence supporting level U recommendation. Similarly, there is no data on the risk of relapse with oral corticosteroids (class IV, level U), compared to ACTH. There is class IV evidence supporting level U recommendation for the safety of oral corticosteroids and class II evidence for level B recommendation for ACTH. In terms of oral corticosteroids and effects on long-term development there is class IV evidence leading to level U recommendation, compared to class III evidence supporting level C recommendation for ACTH. Randomized controlled studies are needed to compare oral corticosteroids with ACTH, the optimal dosage and regimen as well as the long-term neurodevelopmental outcomes. Based on the limited existing studies a treatment guideline for LMIC is proposed which could be used to standardize interventions permitting clarification of these unmet questions. PMID- 29787924 TI - Sleep architecture and epileptic characteristics of drug naive patients in childhood absence epilepsy spectrum. A prospective study. AB - PURPOSE: Childhood absence epilepsy (CAE) is an epileptic syndrome presenting between 2nd-10th years. The spells are elicited with hyperventilation (HV) while sleep seems to exacerbate the electrical activity. Our aim is to describe sleep architecture and its relationship with epileptic discharges (EDs) in patients with CAE, before treatment and one year later. METHODS: Twenty-eight, drug-naive children were recruited (21 girls), mean age 90.1 +/- 32.6 months. Routine-EEG and overnight EEG-polygraphy were conducted upon diagnosis and one year later. Patients were separated in two groups of similar mean age, according to their clinical response at the second recording: group A: children with absolute control of absences and group B: children with partial control. Sleep parameters, EDs and arousals were measured. The effect of medication on sleep parameters was examined, according to 2 groups: valproic-treated and non valproic-treated. RESULTS: Group A showed significant improvement in total sleep time, REM-sleep latency, REM-sleep, arousals-number/hour and arousals-duration/hour between the two recordings. Comparing the two groups for each recording separately, group A initially demonstrated greater epileptic activity and worse sleep parameters, whereas in the second recording exhibited total elimination of the EDs and significantly less arousals. Group B demonstrated persisting EDs and slight deterioration in some sleep parameters during the second recording, despite the lower epileptic load initially. No significant difference was identified between valproic and non-valproic treated patients, regarding the effect on sleep parameters. CONCLUSION: Absolute control of absences and normalization of the electroencephalogram are accompanied by more continuous, stable and efficacious sleep in children with CAE. PMID- 29787925 TI - The association between perceived distress tolerance and cannabis use problems, cannabis withdrawal symptoms, and self-efficacy for quitting cannabis: The explanatory role of pain-related affective distress. AB - Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations. PMID- 29787927 TI - Refugees' admission to mental health institutions in Norway: Is there an ethnic density effect? AB - Some recent European research claims that immigrants settle in urban areas with low scores on level-of-living conditions and a high prevalence of health-risk factors, and that these settlement patterns adversely affect their health. Other studies question the association between immigrant segregation and area deprivation on one hand, and negative health outcomes on the other hand, and identify possible beneficial effects of segregation, specifically the ethnic density effect. This paper aims to explore the possible ethnic density effect among refugees, a sub-population that often appears relatively vulnerable compared with immigrants in general. The data comprise 30 871 individuals, aged 20-69, with an (post-1989) officially registered refugee status from six major countries, including Vietnam, Somalia, Iran, Iraq, Sri Lanka and Bosnia. Two outcomes are analysed, covering the 2008-2011 period - the probability of being admitted at least once to a mental health institution and the number of bed days during that period. The results show that all immigrant clusters have relatively high concentrations of negative level-of-living conditions. Despite this finding, refugees living in clusters tend to have less use of mental healthcare services. The results suggest that for most refugee groups, living in clusters has positive health outcomes. Many countries use settlement policies to direct the inflow of refugees away from immigrant-dense areas. Norway's settlement policy is no exception, aiming at a geographic dispersal of refugees to avoid the emergence of socially segregated urban ethnic communities. This paper discusses the relevance of such a policy for refugees' overall integration and level-of-living conditions. PMID- 29787926 TI - Examining community and consumer food environments for children: An urban suburban-rural comparison in Southwestern Ontario. AB - The aim of this study is to evaluate how retail food environments for children in the City of London and Middlesex County, Ontario, Canada, vary according to level of urbanicity and level of socioeconomic distress. Urbanicity in this study is defined as a neighbourhood's designation as urban, suburban, or rural. We assessed community food environments (e.g., the type, location, and accessibility of food outlets) using 800m and 1600m network buffers (school zones) around all public and private elementary schools, and we calculated and compared density of junk food opportunities (JFO) (e.g., fast food and full-service restaurants, grocery stores, and convenience stores) within each school zone in urban, suburban and rural settings. The study also assessed consumer food environments (e.g., the price, promotion, placement, and availability of healthy options and nutrition information) through restaurant children's menu audits using the Children's Menu Assessment tool. Results suggest JFO density is greater around elementary schools in areas with higher levels of socioeconomic distress and urbanicity, while urbanicity is also associated with greater use of branded marketing and inclusion of an unhealthy dessert on children's menus. PMID- 29787928 TI - Principle of K+/Na+ selectivity in the active site of group II intron at various stages of self-splicing pathway. AB - Group II introns are ribozymes which can catalyze its own splicing and relegate itself. They share common structural features and are evolutionarily related to eukaryotic spliceosome. Hence, group II introns are an excellent model system for understanding the mechanism of RNA-splicing in gene expression. Recent advancement of structural studies has provided x-ray structures of group II intron at different stages (Pre-hydrolytic, post-hydrolytic and free intron) of splicing pathway and revealed heteronuclear metal ion cluster (two potassium; K1 and K2, two magnesium; M1 and M2) in the active site as common structural feature of group II introns. It is believed that these four metal ions are very crucial for catalysis. K+ is very important for the function and buffers containing only Na+ can destroy the function of group II introns. Despite the available 3D structures of different stages of self-splicing, the energetic origin of K+ selectivity over Na+ is not known. However, these structures provide sufficiently good models for directly computing the energetics of K+ vs Na+ discrimination that is required for understanding self-splicing. Here, we report extensive (~550 ns) of structure-based molecular dynamics free energy simulations that quantitatively estimated K1 vs Na1 discrimination. We show that the strength of discrimination varies along the self-splicing pathway. The free and pre hydrolytic states are highly selective for K1 and the selectivity is lost in the post-hydrolytic state. The simulations further reveal that Na1 in the free and pre-hydrolytic state is trapped with an unsatisfied first coordination shell in the active site, which is responsible for large discrimination. The Na1 in the active site of post-hydrolytic state allow water entry and satisfy the Na1 bonding requirement, resulting in low discrimination. The results not only give insights into the experimentally unresolved Na1 bound complexes but also provide the link between structures and computed energetics. PMID- 29787929 TI - Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population: the Hisayama Study. AB - BACKGROUND: Epidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)-namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression. METHODS: A total of 2,529 community-dwelling Japanese residents aged >= 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model. RESULTS: The prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28-13.3) had a 4.10 times (95%CI: 1.13-19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30-1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) >= 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP < 1.0 mg/L. LIMITATIONS: Reverse causality is possible due to the cross-sectional study design. CONCLUSIONS: Our findings suggest that a higher serum AA/EPA ratio is associated with a greater likelihood of depressive symptoms in subjects with systemic inflammation in the general Japanese population. PMID- 29787930 TI - Fibro-osseous pseudotumor of digits - Expanding the spectrum of clonal transient neoplasms harboring USP6 rearrangement. AB - Fibro-osseous pseudotumors of the digits (FOPD) is a rare self-limiting lesion composed of bland looking hypercellular fibrous tissue and bone. USP6 rearrangement is a consistent genetic finding in aneurysmal bone cyst, nodular fasciitis, myositis ossificans and giant cell lesions of small bones. We report herein the occurrence of USP6 rearrangement in fibro-osseous pseudotumors of the digits using fluorescence in situ hybridization analysis (FISH). Of the five patients included, three were female and two were male. The age ranged from 33 to 72 years (mean 48 years). Lesions arose in the palm (n = 2), thenar (n = 1), middle finger (n = 1) and great toe (n = 1). All patients underwent resection. Four cases (80%) harbored USP6 rearrangements showing that fibro-osseous pseudotumors of digits belongs to the spectrum of clonal transient neoplasms including aneurysmal bone cyst, nodular fasciitis, myositis ossificans and giant cell lesion of small bones. PMID- 29787931 TI - Prognostic impact of tumor-stroma ratio in oral squamous cell carcinoma - A pilot study. AB - BACKGROUND: Several prognostic indicators have been used for many decades in an attempt to predict clinical behaviour of Oral Squamous Cell Carcinoma (OSCC). The prognostic value of TSR is yet to be explored in OSCC. Hence, the aim of the present study was to evaluate the prognostic value of TSR in OSCC patients. METHODOLOGY: A cohort of 60 histologically diagnosed cases of OSCC who underwent Radical Neck Dissection was included in the study. TSR was assessed and patients with >50% intratumor stroma were quantified as the stroma-poor group and those with <50% as the stroma-rich group. RESULTS: The parametric tests were performed for the statistical evaluation of TSR with the clinico-pathological variables and the survival. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 95.23% and 69.04%, respectively, in stroma-poor group and 77% and 44%, respectively in the stroma-rich group. CONCLUSION: TSR may serve as a reliable histologic prognostic indicator in OSCC and could be used in routine diagnostic pathology. PMID- 29787932 TI - Initial data on adsorption of Cs and Sr to the surfaces of microplastics with biofilm. AB - The adsorption of radiocesium and radiostrontium onto a range of natural materials has been well quantified, but not for the new media of environmental plastics, which may have enhanced adsorption due to surface-weathering and development of biofilms. Microplastic samples were deployed in freshwater, estuarine and marine conditions, then characterised using infrared spectroscopy to document changes to the plastic surface (vs interior). Synchrotron elemental mapping data revealed surfaces that were well-covered by accumulation of reactive water solutes and sulphur, but, in contrast, had highly discrete coverage of elements such as Fe and Ti, indicating adhered mineral/clay-associated agglomerates that may increase overall adsorption capacity. Plastics that had been deployed for nearly five months adsorbed radionuclides in both freshwater and estuarine conditions with the highest Kd for cesium (Cs) in freshwater (80 ml g-1) and lowest for strontium (Sr) in estuarine conditions (5 ml g-1). The degree of Cs and Sr adsorption onto plastics appears to be approximately 2-3 orders of magnitude lower than for sediment reference values. While lower than for sediments, adsorption occurred on all samples and may indicate a significant radionuclide reservoir, given that plastics are relatively buoyant and mobile in water regimes, and are increasing in global aquatic systems. PMID- 29787933 TI - THD-Tricluster: A robust triclustering technique and its application in condition specific change analysis in HIV-1 progression data. AB - Developing a cost-effective and robust triclustering algorithm that can identify triclusters of high biological significance in the gene-sample-time (GST) domain is a challenging task. Most existing triclustering algorithms can detect shifting and scaling patterns in isolation, they are not able to handle co-occurring shifting-and-scaling patterns. This paper makes an attempt to address this issue. It introduces a robust triclustering algorithm called THD-Tricluster to identify triclusters over the GST domain. In addition to applying over several benchmark datasets for its validation, the proposed THD-Tricluster algorithm was applied on HIV-1 progression data to identify disease-specific genes. THD-Tricluster could identify 38 most responsible genes for the deadly disease which includes GATA3, EGR1, JUN, ELF1, AGFG1, AGFG2, CX3CR1, CXCL12, CCR5, CCR2, and many others. The results are validated using GeneCard and other established results. PMID- 29787935 TI - Functional characterization of the eugenol synthase gene (RcEGS1) in rose. AB - The floral volatile compound eugenol is an important constituent in many aromatic plants, being a floral attractant for pollinators as well as having antimicrobial activity. Rose flowers emit eugenol and its derivatives. We recently reported a eugenol synthase gene (RcEGS1) (JQ522949) that was present in petals of R. chinensis cv. Old Blush. RcEGS1 has its highest expression levels in the petals compared to other tissues; it has higher transcript levels at the developmental blooming stage and lower levels at budding and senescence stages. Here, we overexpressed the RcEGS1 protein in Escherichia coli, and showed by Western-blot analysis that its expression was mainly detected in stamens and petals at the flower opening stage. RcEGS1 was principally localized in the upper and lower epidermal layers, which are the major sites of scent emission in roses. Furthermore, we demonstrated that down-regulation of RcEGS1 expression in flowers by virus-induced gene silencing led to a reduction of the relative content of eugenol. We suggested that RcEGS1 was responsible for eugenol biosynthesis in roses. PMID- 29787936 TI - Dynamic remobilization of leaf nitrogen components in relation to photosynthetic rate during grain filling in maize. AB - Remobilization of leaf nitrogen (N) contributes greatly to grain N in maize, but leads to low photosynthetic rate (Pn). Pn is determined by various N components involving in light harvest and CO2 reduction. However, it is less clear which N component is the major contributor for the reduction of photosynthesis in modern stay-green maize hybrids. In this study, we analyzed the relationship between remobilization of different N components and Pn during grain filling stage under low N (no N application) and high N (180 kg N ha-1) in a field experiment. The remobilization efficiency of photosynthetic enzymes (PEPc, PPDK and Rubisco) in the leaf was much higher than that of thylakoid N and other N components. Low N supply increased the remobilization efficiency of all the leaf N components. During grain filling stage, the amount of all the N components decreased together with Pn. The ratio of Pn to the N in the PEPc, PPDK and Rubisco kept increase in the whole grain filling stage, while the ratio of Pn to chlorophyll and thylakoid N decreased. Correlation analysis indicated that Pn was more related to the content of photosynthetic enzymes than to chlorophyll and thylakoid N. It is concluded that photosynthetic enzymes serve as an N storage reservoir at early grain filling stage and their degradation is critical in the reduction of Pn during later grain filling stage. Future breeding targets may be focused on enhancing the efficiency of photosynthetic enzymes during late grain filling stage. PMID- 29787934 TI - How (not) to interpret a non-causal association in sports injury science. AB - OBJECTIVE: To discuss the interpretability of non-causal associations to sports injury development exemplified via the relationship between navicular drop (ND) and running-related injury (RRI) in novice runners using neutral shoes. DESIGN: 1 year prospective cohort study. SETTING: Denmark. PARTICIPANTS: 926 novice runners, representing 1852 feet, were included. MAIN OUTCOME MEASURE: The outcome was "a musculoskeletal complaint of the lower extremity or back caused by running, which restricted the amount of running for at least a week". RESULTS: Fewer feet with small ND than those feet with a reference ND sustained injuries at 50 (risk difference (RD) = -4.1% [95%CI = -7.9%;-0.4%]) and 100 km (RD = -5.3% [95%CI = -9.9%;-0.7%]). Similarly, fewer feet with a large ND sustained injuries than the feet with a reference drop at 250 (RD = -7.6% [95%CI = -14.9%;-0.3%]) and 500 km (RD = -9.8% [95%CI = -19.1%;-0.4%]). CONCLUSION: Non-causal associations can help to identify sub-groups of athletes at an increased or decreased risk of sports injury. Based on the current results, those with a small or large navicular drop sustain fewer injuries than those with a reference drop. Importantly, navicular drop does not cause RRIs, but influences the relationship between training load and RRI. This illustrates that non-causal associations are unsuitable to respond to the question: Why do sports injury develop? PMID- 29787937 TI - Can working memory training improve children's sleep? AB - BACKGROUND: Improving children's sleep could lead to significant benefits in several functional domains. Recent research in adults suggests that intensive, adaptive cognitive training may be beneficial in improving sleep, although there is limited understanding whether this approach yields similar results in children. OBJECTIVE: To determine whether a working memory training program improved sleep latency, sleep problems, and sleep duration on school and nonschool nights and whether there was a differential effect of the timing of training during the school day on sleep outcomes. DESIGN/METHODS: Design: Population-based randomised controlled trial. SETTING: Forty-four schools in Melbourne, Australia. PARTICIPANTS: All Grade 1 children (mean age = 6.9 years, SD 0.4) underwent WM screening using two subtests from the Automated Working Memory Assessment. Children with low verbal and/or visuo-spatial WM scores relative to their peers ('low WM', ~25%) were randomised to intervention or control arms. INTERVENTION: 20 to 25 computerised 25-min training sessions were conducted using the CogMed program, over 5-7 weeks at school. OUTCOMES: Parent reported child sleep characteristics (time, latency, duration and problem) at 6 months post randomisation. RESULTS: A total of 452 (26.0%) of 1723 children screened (64.1% of approached) met trial eligibility criteria, with 226 in each study arm. Of intervention children, 91% completed the minimum 20 days of training. Retention was 90.5% at 6 months. Adjusted regressions showed that intervention children did not have better sleep latency, duration, bedtime consistency or less sleep problems. CONCLUSION: It does not appear that adaptive working memory training during the school day can be used as a novel approach to improve children's sleep attributes up to 6 months post-randomisation, regardless of the time of day training is delivered. PMID- 29787938 TI - Historical overview of lymphangiogenesis. AB - The investigation of the lymphatic system has a very long and intriguing history, with several medical figures which brought important contributions. Work on the lymphatic system began in the 17th century, and by the beginning of the 19th century the anatomy of most of the lymphatic system had been described. This system is an essential component of the immune system, as well as vital to the maintenance of fluid homeostasis within the body. In this review article, I summarize the most important contributions to this field, until to the discovery of a specific lymphangiogenic factor, namely vascular endothelial growth factor-c (VEGF-C) (summarizing figure). PMID- 29787939 TI - DigBody(r): A new 3D modeling tool for nasal virtual surgery. AB - BACKGROUND AND PURPOSE: Recent studies have demonstrated that a significant number of surgical procedures for nasal airway obstruction (NAO) have a high rate of surgical failure. In part, this problem is due to the lack of reliable objective clinical parameters to aid surgeons during preoperative planning. Modeling tools that allow virtual surgery to be performed do exist, but all require direct manipulation of computed tomography (CT) or magnetic resonance imaging (MRI) data. Specialists in Rhinology have criticized these tools for their complex user interface, and have requested more intuitive, user-friendly and powerful software to make virtual surgery more accessible and realistic. In this paper we present a new virtual surgery software tool, DigBody(r). METHODS: This new surgery module is integrated into the computational fluid dynamics (CFD) program MeComLand(r), which was developed exclusively to analyze nasal airflow. DigBody(r) works directly with a 3D nasal model that mimics real surgery. Furthermore, this surgery module permits direct assessment of the operated cavity following virtual surgery by CFD simulation. RESULTS: The effectiveness of DigBody(r) has been demonstrated by real surgery on two patients based on prior virtual operation results. Both subjects experienced excellent surgical outcomes with no residual nasal obstruction. CONCLUSIONS: This tool has great potential to aid surgeons in modeling potential surgical maneuvers, minimizing complications, and being confident that patients will receive optimal postoperative outcomes, validated by personalized CFD testing. PMID- 29787940 TI - Survey on deep learning for radiotherapy. AB - More than 50% of cancer patients are treated with radiotherapy, either exclusively or in combination with other methods. The planning and delivery of radiotherapy treatment is a complex process, but can now be greatly facilitated by artificial intelligence technology. Deep learning is the fastest-growing field in artificial intelligence and has been successfully used in recent years in many domains, including medicine. In this article, we first explain the concept of deep learning, addressing it in the broader context of machine learning. The most common network architectures are presented, with a more specific focus on convolutional neural networks. We then present a review of the published works on deep learning methods that can be applied to radiotherapy, which are classified into seven categories related to the patient workflow, and can provide some insights of potential future applications. We have attempted to make this paper accessible to both radiotherapy and deep learning communities, and hope that it will inspire new collaborations between these two communities to develop dedicated radiotherapy applications. PMID- 29787941 TI - Effect of egg yolk plasma and soybean lecithin on rooster frozen-thawed sperm quality and fertility. AB - This experiment was conducted to study the effects of egg yolk plasma (10%, 15% and 20%), soybean lecithin (0.5%, 1% and 1.5%) and whole egg yolk (WEY) (control) on post-thawed sperm quality, hatchability and fertility outcomes. In experiment 1, sperm motility, abnormalities, membrane integrity, viability, apoptosis status, mitochondrial activity were studied following freeze-thawing. The best quality of frozen-thawed rooster sperm was chosen to be used for the assessment of the hatchability and fertility rate in experiment 2. The significantly higher percentages of post-thawing sperm total and progressive sperm motilities, membrane integrity, viability were observed in 1% soybean lecithin and 20% egg yolk plasma in comparison with 0.5 and 1% soybean lecithin, 10% egg yolk plasma and control, except for 15% egg yolk plasma (P < 0.05). Using 20% egg yolk plasma in the extender improved mitochondrial activity. Supplementation of 1% soybean lecithin and 20% egg yolk plasma into the extender resulted in the least percentages of dead sperm (P < 0.05). Sperm abnormalities and early apoptosis did not differ in various extender supplementations. In experiment 2, higher percentages of hatchability and fertility rate were observed in semen containing 1% soybean lecithin and 20% egg yolk plasma compared with the WEY group. The results showed that supplementation of the rooster sperm extender with 1% soybean lecithin and 20% egg yolk plasma resulted in higher quality of frozen-thawed sperm. PMID- 29787942 TI - Thrombotic and hemorrhagic complications in children and young adult recipients of Hematopoietic Stem Cell Transplant (HSCT). AB - BACKGROUND: Overall incidence of hemostatic complications in pediatric recipients of Hematopoietic Stem Cell Transplant (HSCT) is scarcely studied. This retrospective review explored the incidence and underlying risk factors of bleeding and thrombotic complications in children. PROCEDURE: Clinical characteristics, hemorrhagic events (HE), thrombotic events (TE) and follow up data were abstracted from medical records on patients aged <21 years undergoing HSCT during January 2000-June 2015. RESULTS: From start of conditioning until last follow up, 238 pediatric patients were reviewed during this study. There were 16 symptomatic thrombotic complications in 15 patients, along with 13 major bleeding events. Incidence of HE or TE was higher in allogeneic HSCT compared to autologous HSCT (p = 0.02). Severe thrombocytopenia could not be identified as a major contributor to bleeding. All patients with HE had platelets between 20,000 50,000 * 109/L, except one patient, who had platelets <20,000 * 109/L. All patients with hemorrhagic cystitis (n = 7) had received cyclophosphamide (Cy). For patients with sinusoidal obstruction syndrome, conditioning included either busulfan (Bu)/Cy (n = 5), Cy with total body irradiation (n = 4), or thiotepa (n = 2). Among allogeneic HSCT recipients, 60% of HE and 92% with TE had underlying myeloid neoplasms. Graft versus Host disease contributed to both types of complications (p = 0.07), although not reaching statistical significance. CONCLUSIONS: Allogeneic pediatric HSCT patients had higher overall risk of hemorrhagic or thrombotic complications compared to autologous recipients in this study. HSCT for myeloid malignancies was a risk factor for higher complications. PMID- 29787943 TI - Venous thromboembolism with EGFR monoclonal antibody necitumumab in stage IV non small cell lung cancer: A retrospective cohort analysis. AB - INTRODUCTION: Metastatic non-small cell lung cancer (NSCLC) is a recognized risk factor for VTE. Some systemic treatments may increase this risk further. Here, we present the risk of VTE and its prognostic significance for patients treated with chemotherapy (chemo) and the EGFR monoclonal antibody necitumumab (neci) for metastatic NSCLC. METHODS: Four trials of 1st-line treatment for Stage IV NSCLC were analyzed: two randomized phase 3 studies of cisplatin/gemcitabine +/-neci in squamous NSCLC (SQUIRE: N = 1079) and cisplatin/pemetrexed +/-neci in non squamous NSCLC (INSPIRE: N = 616); JFCL (N = 161), a randomized phase 2 trial of carboplatin/paclitaxel +/-neci in squamous NSCLC; and JFCK (N = 61), a single arm phase 2 trial of cisplatin/gemcitabine +neci in squamous NSCLC. A Cox proportional hazards model with VTE as a time-dependent covariate was used for overall survival (OS) analyses. RESULTS: Neci + chemo was associated with an increased risk of VTE (Relative Risk [RR]: 1.579; 95% CI: 1.155-2.158). History of VTE (RR: 1.899; 95% CI: 1.142-3.156) and prior cardiac/cardiovascular events (RR: 1.514; 95% CI: 1.102-2.082) were associated with increased risk of VTE. Decreased VTE risk was seen with: male sex (RR: 0.696; 95% CI: 0.502-0.964), eastern European geographic region (RR: 0.387; 95% CI: 0.267-0.562) and squamous cell pathology (RR: 0.653; 95% CI: 0.483-0.883). VTE occurrence showed no association with OS (HR: 1.121; 95% CI: 0.930-1.351). CONCLUSION: Our data suggest that certain patient characteristics such as prior history of VTE and non squamous histology might be associated with an increased risk of on-treatment VTE in NSCLC, although in this study, overall survival was not affected. Further studies to develop measures for identifying high-risk patients are needed to inform treatment decisions as well as VTE management and prophylaxis. PMID- 29787944 TI - Statin exposure and thrombosis risk in patients with myeloproliferative neoplasms. PMID- 29787945 TI - Sex-specific age threshold for increased risk of retinal vein occlusion in Koreans. AB - PURPOSE: Retinal vein occlusion (RVO) is one of most common retinal vascular disorders. It can lead to visual impairment and subsequent socioeconomic loss among the working population. RVO peak incidence is known to occur in the fifth and sixth decades of life, and is more predominant in males. To date, there has been no consensus regarding the optimal screening age for individuals at high risk for RVO, or whether sex-dependent cut-offs may be appropriate. Therefore, the purpose of this study was to predict the sex-specific age threshold for increased risk of RVO in Koreans. METHODS: The analysis was based on data from the Korean National Health Insurance Database from 2013. Patients diagnosed with new cases of RVO from January 2013 to December 2013 were included. Individuals younger than 20 years of age and those with other retinal diseases were excluded. Multivariate logistic regression analysis and odds ratios with 95% confidence intervals were conducted to identify the age-related risk factors for RVO. A receiver operating characteristic (ROC) curve for RVO incidence was constructed. RESULTS: Among the 754,749 individuals included in the study, 623 (0.08%) developed RVO. The optimal cut-off age for increased risk of RVO was 54 years overall, (sensitivity 0.78, specificity 0.70), 48 years in males (sensitivity 0.90, specificity 0.58), and 54 years in females (sensitivity 0.80, specificity 0.68). The incidence of RVO in females over 50 years of age was 3 times higher than that in females under the age of 50 after adjusting for confounding factors, and these differences tended to increase with age. The area under the ROC curve was 0.80 (95% CI; 0.79-0.82) overall, 0.81 (95% CI; 0.79-0.83) in males, and 0.79 (95% CI; 0.78-0.81) in females. CONCLUSION: RVO incidence was higher in females, and increased more rapidly with age. The incidence of RVO more than doubled after 50 years of age for both sexes after adjusting for confounding factors. Females had an older age cut-off for RVO than males. However, the clinical impact of the use of sex-specific age cut-offs for RVO would benefit from additional validation from further studies. PMID- 29787946 TI - Environmentally durable superhydrophobic surfaces with robust photocatalytic self cleaning and self-healing properties prepared via versatile film deposition methods. AB - Superhydrophobic (SH) surfaces with self-cleaning photocatalytic properties have become an important research focus in recent years. In this work, we fabricated multifunctional and environmentally durable SH surfaces via a facile one-step reaction of octadecyl isocyanate (ODI) with TiO2 particles. The resulting films possess SH properties, facilitated by a combination of hydrophobic long alkyl chains and the hierarchical crystalline structure. Films can be prepared via spray or blade coating on a variety of hard and soft substrates, and function well when exposed to either air or oil. The coating retains its SH properties for at least 6 months in ambient conditions, and after organic pollution it can recover its SH properties using UV or sun light illumination. After water impalement, the SH properties can self-heal via the self-assembly of long alkyl chains to their original state within several hours at ambient conditions, or within minutes on a heating stage. The covalent bonds between alkyl chains and TiO2, together with hydrogen bonds between adjacent alkyl chains, greatly increased the surface durability of the SH films. This multifunctional SH coating is a very promising material for commercial and industrial coating applications. PMID- 29787947 TI - Supramolecular proteinaceous biofilms as trapping sponges for biologic water treatment and durable catalysis. AB - Inspired by the bacterial biofilms and chorions of living organisms which are made by proteinaceous assemblies and functional for multi-applications, various artificial protein fibrils-based nanoporous films are developed, and show their potential applications in multiple fields. Here, a simple and environmental friendly method was identified to produce bovine serum albumin (BSA) nanofibrils based biofilms, through a combination of protein fibrillation and reverse dialysis. BSA nanofibrils formed biofilms through intermolecular interactions, the resultant biofilms showed tunable thickness by altering the initial protein amount, good stability in organic and salty solvents, transparency and fluorescence properties, hold high capacity of trapping different substances (e.g. nanomaterials, organic dyes, heavy-metal ions and enzymes), and further enabled applications in biologic water treatment and enzyme stabilization. Taken o-phenylenediamine as substrate, the trapped horseradish peroxidase showed a catalytic activity 9-38 folds higher than free ones in organic phase, together with enhanced stability. These protein nanofibrils-based films offered an attractive biologic platform to hybridize diverse materials for on-demand functions and applications. PMID- 29787948 TI - Preparation and application of a molecular capture for safety detection of cosmetics based on surface imprinting and multi-walled carbon nanotubes. AB - A novel composite material for prednisone molecular capture (PS-MC) was prepared by surface imprinting technique in combination with a polyethylene filter plate coated with multi-walled carbon nanotubes for the first time. PS-MC was achieved by using prednisone as the template molecule, 3-aminopropyltriethoxysilane as the monomer, and tetraethoxysilane as the cross-linker. The structure, morphology, and thermal stability of the prepared PS-MC were studied by fourier-transform infrared spectrometry, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and thermogravimetric analysis. PS-MC was assessed by re-binding experiments such as adsorption kinetics, adsorption isotherms, molecular identification, and applied to the separation and enrichment of prednisone in cosmetics. The results indicated that PS-MC has rapid binding kinetic, high adsorption capacity, and favorable reusability. The imprinted materials were coupled with HPLC to selectively separation, purification, and detection of prednisone from spiked cosmetic samples. The recoveries of spiked cosmetic samples were in the range of 83.0-106.0%, with relative standard deviations of less than 2.10%, and the limit of detection of 5 ng/mL (S/N = 3). PMID- 29787949 TI - Liquid-phase laser ablation synthesis of graphene quantum dots from carbon nano onions: Comparison with chemical oxidation. AB - Graphene quantum dots (GQDs) have been synthesized reproducibly by chemical oxidation (CO) of carbon nano-onions (nCNOs) and a one-step pulsed laser ablation (LA) of nCNOs in deionized water. The photoluminescence (PL) spectra show that the LA-GQDs have blue shifted emission relative to the CO-GQDs which is attributed to the effects of both particle sizes and surface functional groups. The CO-GQDs have an average diameter of 4.1(8) nm and a thickness corresponding to two or three graphene layers, while the LA-GQDs have an average diameter of 1.8(6) nm and a thickness comparable to a single layer of graphene. The CO-GQDs favor the presence of carboxylic groups and have a higher fraction of sp2 carbons, while the LA-GQDs prefer the presence of hydroxyl groups and have a higher fraction of sp3 carbons. PL lifetime data suggests that surface functional groups are the main source of radiative deactivation and the sp2 carbon domains are mainly responsible for non-radiative decay. PL lifetimes are measured to be 7.9(6) ns for the emission from the carboxylic groups and 3.18(10) ns from the hydroxyl groups. Compared to CO, liquid-phase LA is a faster and cleaner one-step method for producing GQDs with fewer starting chemicals and byproducts. PMID- 29787950 TI - Macroporous silica nanoparticles for delivering Bcl2-function converting peptide to treat multidrug resistant-cancer cells. AB - The abundance of B cell lymphoma gene 2 (Bcl-2) is closely correlated with the resistance of cancer cells to chemotherapeutic agents, and a peptide derived from orphan nuclear receptor Nur77 can convert Bcl-2 from a protector to a killer of cancer cells. However, successful application of the Bcl-2-converting peptide to treat drug-resistant cancer cells depends on an efficient delivery carrier. Mesoporous silica nanoparticles (MSNs) have been extensively studied as promising candidates for small molecule drug delivery. However, the effective encapsulation and intracellular delivery of peptides using small pore-sized MSNs still remain a great technical challenge. In this paper, an effective delivery platform for Bcl 2-converting peptide was fabricated by us to treat multidrug resistant-cancer cells via tuning the surface functionality of macroporous silica nanoparticles. The resulting large-sized pore silica nanoparticles, especially those modified with thiol group, exhibited the high Bcl-2-converting peptide-loading efficiency of over 40%. Moreover, the peptide induced MCF7/DOX cells into apoptotic status by penetrating cytomembrane into mitochondria and being bound with Bcl-2 to expose the BH3 domain with the aid of various surface functionalities-decorated MSNs. In particular, amine-modified surface of MSNs caused the greater influence on the cell apoptosis-inducing effects of peptide in comparison with other functionalities-modified ones. Taken together, our study, for the first time, demonstrates a special approach towards pore size and surface functionality collectively modulated silica-based nanostructural material for effective delivery of bio-macromolecules (e.g., Bcl-2-converting peptide) to treat the multidrug resistant-cancer cells with elevated Bcl-2 levels. PMID- 29787951 TI - Glutathione-triggered dual release of doxorubicin and camptothecin for highly efficient synergistic anticancer therapy. AB - An amphiphilic biodegradable prodrug (PLG-g-mPEG/CPT) was synthesized by conjugating disulfide-containing camptothecin (CPT) to poly(L-glutamic acid) graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) through esterification reaction. The amphiphilic prodrugs could self-assemble into micellar nanoparticles and encapsulate doxorubicin (DOX) in aqueous solution at pH 7.4. The treatment of the nanoparticles with reducing glutathione (GSH) at cytosolic concentration (10 mM) significantly promoted the in vitro dual release of DOX and CPT from the micelles. The results of flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) manifested that the intracellular release of DOX and CPT from the micelles was enhanced by increasing the intracellular GSH level. Consistently, the MCF-7 cell killing mediated by the micelles was also intracellular GSH concentration-dependent. The low combination index (CI) value of < 0.3 demonstrated the high synergistic effect of DOX and CPT co-delivered by the nanoparticles in tumor cell killing. Therefore, this GSH-triggered dual release drug delivery system is a promising strategy for combination cancer therapy. PMID- 29787952 TI - Effects of partially saturated conditions on the metabolically active microbiome and on nitrogen removal in vertical subsurface flow constructed wetlands. AB - Nitrogen dynamics and its association to metabolically active microbial populations were assessed in two vertical subsurface vertical flow (VF) wetlands treating urban wastewater. These VF wetlands were operated in parallel with unsaturated (UVF) and partially saturated (SVF) configurations. The SVF wetland exhibited almost 2-fold higher total nitrogen removal rate (5 g TN m-2 d-1) in relation to the UVF wetland (3 g TN m-2 d-1), as well as a low NOx-N accumulation (1 mg L-1 vs. 26 mg L-1 in SVF and UVF wetland effluents, respectively). After 6 months of operation, ammonia oxidizing prokaryotes (AOP) and nitrite oxidizing bacteria (NOB) displayed an important role in both wetlands. Oxygen availability and ammonia limiting conditions promoted shifts on the metabolically active nitrifying community within 'nitrification aggregates' of wetland biofilms. Ammonia oxidizing archaea (AOA) and Nitrospira spp. overcame ammonia oxidizing bacteria (AOB) in the oxic layers of both wetlands. Microbial quantitative and diversity assessments revealed a positive correlation between Nitrobacter and AOA, whereas Nitrospira resulted negatively correlated with Nitrobacter and AOB populations. The denitrifying gene expression was enhanced mainly in the bottom layer of the SVF wetland, in concomitance with the depletion of NOx-N from wastewater. Functional gene expression of nitrifying and denitrifying populations combined with the active microbiome diversity brought new insights on the microbial nitrogen-cycling occurring within VF wetland biofilms under different operational conditions. PMID- 29787954 TI - The effectiveness of a cognitive training program in people with mild cognitive impairment: A study in urban community. AB - OBJECTIVE: To assess the effectiveness of a cognitive training program on global cognition among people with mild cognitive impairment. METHODS: In this experimental study, using purposive sampling, 60 participants age 50 years and over who complained of subjective memory impairment were screened in their communities by public health volunteers with the Abbreviated Mental Test. Those with dementia were excluded as well as those with depression, which were screened out by the Thai Geriatric Depression Scale (TGDS-15). Mild cognitive impairment was diagnosed and confirmed by the Montreal Cognitive Assessment (MoCA) and joint agreement between a psychiatrist and a neurologist. The participants were alternately assigned to receive a cognitive training program (intervention group) while the other half received their normal usual therapy (control group). The program involved training of 4 aspects of cognition through 6 sessions; 2 sessions per month for 3 months. The MoCA and TGDS-15 scales were given at baseline and again at week 13, and at months 6 and 9. Independent t-tests were used to compare changes in global cognition among the two groups. RESULTS: MoCA scores at 9 months were significantly higher than at baseline in both groups. However, the mean difference in intervention group was significantly higher than control group. TGDS-15 scores at 6 months was significantly lower than at baseline among the intervention group but not the control group. CONCLUSION: This cognitive training program helped to improve global cognition and reduce depressive symptoms. PMID- 29787953 TI - Public perceptions toward mental illness in Japan. AB - AIM: The purpose was to characterize public perceptions in Japan of mental illness and how they related to stigma-related attitudes for the same. METHODS: Data were obtained using a vignette survey conducted as a part of the Stigma in Global Context - Mental Health Study and contained a nationally representative sample (n = 994). The survey was conducted using a multi-mode approach (face-to face interviews, the drop-off-and-pick-up, postal collection) from September to December 2006, with a multi-stage probability sample of Japanese residents aged 18-64 years. Respondents were randomly assigned one of four vignette conditions that described psychiatric disorders meeting the diagnostic criteria for schizophrenia and major depressive disorder (one vignette for each gender exhibiting each diagnosis). We compared respondents' stigma-related attitudes and perceptions toward mental illness between vignettes. RESULTS: Over 80% of Japanese participants believed that depressive disorder or schizophrenia could be cured via treatment. However, Japanese people still had relatively strong vigilance and denial of competency toward schizophrenia. CONCLUSIONS: Participants expressed the belief that mental illnesses are curable, but stigma toward people with schizophrenia was still relatively strong. PMID- 29787955 TI - Lower P300 amplitudes for internally-generated events in patients with schizophrenia. AB - BACKGROUND: Patients with schizophrenia demonstrate difficulty differentiating internally-generated from externally-generated events. An excessive deployment of attention to external events as well as poor processing of self-generated events has been proposed to explain this misattribution. This study was done to understand the neurophysiological basis of source monitoring bias in schizophrenia. METHODS: Seventeen patients and fourteen healthy controls completed a two-stage source monitoring task involving solving a three-letter jumbled word either by the participant or a computer following which they had to identify the correct source of the word - solved by self (internal source monitoring, ISM) or by computer (external source monitoring, ESM) - while EEG was recorded. P300 amplitude and latency were computed separately for ISM and ESM conditions. RESULTS: P300 amplitude for ISM condition was lower in patients with schizophrenia compared to controls over right and left parietal regions. Additionally, P300 amplitude for ISM condition was lower compared to ESM condition in patients over right and left parietal regions. However, P300 amplitude for ESM condition did not differ significantly between the groups. In contrast to P300 amplitude, there was no significant difference in P300 latency in ISM or ESM condition within or between the groups. CONCLUSION: P300 amplitude was lower for internally-generated but not externally-generated events in patients with schizophrenia. These findings suggest that patients allocate less attentional resources to internally generated events resulting in poorer processing and consequent misattribution of their source of origin. This study provides the first specific electrophysiological evidence of impaired source monitoring in schizophrenia. PMID- 29787956 TI - Gender, self-rated health and functional decline among community-dwelling older adults. AB - OBJECTIVE: This paper examines the association between self-rated health (SRH) and functional decline (FD) in older Ghanaian cohorts and investigates whether the effect differs by gender and also modified by marital status. METHODS: The study used cross-sectional survey data (N = 1200) from an Aging, Health, Psychological Wellbeing and Health-seeking Behavior Study (AHPWHB) study conducted in between August 2016 and January 2017. A four-level gendered stratified logit modeling estimated the SRH-FD association and the interaction terms. RESULTS: Overall, 23% of male respondents and 34% of women revealed significant FD (p < 0.001). The fully-adjusted model showed that SRH status was a strong predictor of FD across genders but the effect was most pronounced among men. Compared with excellent/very good SRH, fair and poor SRH (beta = 0.160; p < 0.05) and (beta = 1.700; p < 0.001) for women and (beta = 2.202; p < 0.001) and (beta= 2.356; p < 0.001) for men respectively were significantly associated with increased FD. However, good (beta = - 1.760; p < 0.001), fair (beta = - 2.800; p < 0.001) and poor SRH (beta = -2.088; p < 0.001) decreased FD if an older woman was married compared with unmarried women with excellent/very good SRH. CONCLUSION: The strength of SRH-FDs association largely differed with gender and also moderated by marital status for women. Improving the SRH and marital quality could be protective of functional abilities, independence and quality of life for older people. PMID- 29787957 TI - Prolonged performance-related neuroendocrine activation and perseverative cognition in low- and high-anxious university music students. AB - Music performances are social-evaluative situations that can elicit marked short term neuroendocrine activation and anxious thoughts especially in musicians suffering from music performance anxiety (MPA). The temporal patterns of neuroendocrine activity and concert-related worry and rumination (perseverative cognition, PC) days before and after a concert in low- and high-anxious musicians are unknown. The first goal of the present study was to investigate the prolonged effects of a solo music performance and the effects of trait MPA on salivary cortisol (sC), alpha-amylase (sAA), and concert-related PC. The second goal was to investigate whether concert-related PC is associated with neuroendocrine activity and mediates the effects of measurement day and trait MPA on neuroendocrine responses. Seventy-two university music students collected saliva samples and reported their PC for seven consecutive days. On the fifth day, they performed solo. Measurement day and trait MPA were tested as main predictors of the diurnal area under the curve with respect to ground (sC AUCg, sAA AUCg), awakening responses, and PC. SC AUCg, sAA AUCg, and concert-related PC were highest on concert day. SC AUCg decreased only partially on post-concert days. SAA AUCg remained elevated on the first post-concert day among students with moderate to very high trait MPA. Throughout the assessment period, trait MPA was associated with smaller sC AUCg and higher concert-related PC. Concert-related PC showed significant positive associations with sC AUCg and sAA AUCg but did not mediate the effects of measurement day and trait MPA on these measures. These findings suggest that solo music performances have prolonged neuroendocrine effects and that trait MPA is an important factor having specific effects on university music students' hypothalamic-pituitary-adrenal axis, autonomic nervous system, and cognitive activity. PMID- 29787958 TI - Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes. AB - BACKGROUND: Tryptophan depletion is a well-replicated biological finding in Major Depressive Disorder (MDD). The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme, indolamine 2,3 dioxygenase (IDO), have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, providing a putative link between inflammation and neuropathology. This study examined circulating concentrations of C-reactive protein (CRP), plasma tryptophan, kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) and whole blood mRNA expression of IDO in patients with major depressive disorder (MDD) compared with healthy controls (HC). METHODS: A diagnosis of major depression was made according to DSM-IV. Depression severity was assessed using the Hamilton depression (HAM-D) rating scale. 74 MDD patients, 39 with a first presentation of MDD (fpMDD) and 35 with chronic or recurrent episodes (rMDD), and 37 HC were recruited to the study. Whole blood and plasma samples were collected. Expression of markers in whole blood were measured by PCR, circulating CRP by ELISA and KP metabolites by LC-MS/MS. Hippocampal cornu ammonis (CA) and subiculum volumes were determined by MRI and calculated using FreeSurfer. RESULTS: Tryptophan concentrations were significantly reduced in MDD compared to HC. There was a positive correlation between QUIN and both CRP concentrations and whole blood IDO1 in MDD. KYNA concentrations were reduced in MDD patients presenting with a first episode (fpMDD) compared to those presenting with recurrent depression (rMDD) and HC. By contrast QUIN concentrations were elevated in rMDD compared to fpMDD and HC. KYNA/QUIN was reduced in MDD and rMDD but not fpMDD compared to HC. Hippocampal subfield volumes were smaller in MDD patients than HC for CA1 (left only), CA2/3 (left and right) and CA4 (right only). CRP and CA1 volumes were negatively correlated bilaterally in MDD patients. KYNA and subiculum volume were positively correlated bilaterally. DISCUSSION: This study found evidence of KP metabolism imbalance in MDD patients in addition to tryptophan reduction and mild immune activation. Relationships between CRP and KYNA with some hippocampal subfield volumes in MDD patients suggest that this inflammatory signature may be associated with reduced hippocampal subfield volumes in depression. PMID- 29787960 TI - Late presentation of ectopia vesica with malignant transformation. A case report and review. AB - INTRODUCTION: Exstrophy of the bladder is a rare congenital anomaly usually treated in neonatal or childhood period. When combined with renal agenesis and presents for the first time in the adulthood with malignant transformation, is an extreme rarity. CASE PRESENTATION: We present a case of 65 years single male who presented with a right irreducible inguinal hernia and an unreconstructed Ectopia Vesicae with fungating tumor. He was anemic with impaired renal function, left renal agenesis and right sided hydronephrosis, hydroureter and distal ureteric stricture. He underwent palliative excision of Ectopia Vesicae and urinary diversion via ureterosegmoidostomy after his condition was optimized. Histopathology showed metaplastic squamous mucosa and a moderately differentiated mucinous adenocarcinoma. Three weeks later he had good continence and normal renal function. He was sent to a distant radio-oncology center for further management. DISCUSSION: In 1851 the first ureterosegmoidostomy for ectopia vesicae was done. Later on it becomes more popular. Some people preferred deferring it until the age of 4 years while others advocates earlier reconstruction. Plastic operation, during neonatal life was also described. In the majority of cases, the fibrotic nature of the bladder and the absence of the sphincter make the reconstruction almost impossible. We performed the only possible option in our setting as our patient had a complex congenital anomalies which present late in life complicated with advanced malignant transformation. CONCLUSION: Despite the plethora of congenital malformation and advanced malignancy, surgical excision and diversion with adjuvant chemo-radiation provided a good palliation for this patient. PMID- 29787959 TI - High-voltage electrical injury complicated by compartment syndrome and acute kidney injury with successful limb salvage: A case report and review of the literature. AB - INTRODUCTION: Although an uncommon form of admission to a burns centre, the deep, penetrating nature of noxious currents mean that electrical burns have the most catastrophic consequences of all burn injuries. Understanding the physics of electricity is crucial to explaining the mechanisms of tissue damage and organ failure in electrical injuries which necessitate special management above and beyond that of regular thermal burns. PRESENTATION OF CASE: We present a young man who suffered significant occupation-related electrical burns that was complicated by compartment syndrome, rhabdomyolysis and acute kidney injury. He required multiple surgeries (including fasciotomy as well as soft tissue reconstruction), critical care and lengthy rehabilitation. DISCUSSION: Rhabdomyolysis is common sequela of electrical burns and may result in severe and permanent metabolic and renal impairment. High cut-off dialysis membranes have shown great promise in myoglobin removal but further studies are required to determine whether this improves clinical outcomes. Debridement and decompression are the cornerstones of initial surgical intervention and are crucial to minimising infectious complications and preserving vital structures. Free tissue transfer has become increasingly popular, but the ideal timing of microsurgery is still uncertain. Nonetheless, pedicled flaps remain widely used and still have an important role in reconstruction of electrical burns. CONCLUSION: Patients with electrical injuries have several unique acute manifestations that differ from other burns. Prognosticating outcomes is difficult, as the full scale of damage is seldom immediately evident. Multiple organ systems are often affected, which makes the treatment of such patients exceptionally challenging, multi disciplinary and resource-intensive. PMID- 29787961 TI - Functional outcome and social cognition in bipolar disorder: Is there a connection? AB - BACKGROUND: Interest in social cognition in bipolar disorder (BD) has increased considerably over the past decade, with studies highlighting major impairments, especially in mental state reasoning, even during euthymia. A causal relationship between social cognition deficits and social functioning has already been established in individuals with schizophrenia, but there is still little information about links between social cognition and social functioning in BD. Our aim was therefore to review the relationship between functional outcome and social cognition in patients with BD. METHODS: We conducted a systematic review of the literature. Relevant articles were identified through literature searches in the MEDLINE/PubMed, EBSCOHost and Google Scholar databases for the years 2000 2017, using the keywords bipolar, social cognition, theory of mind, mentalizing, emotion recognition, emotion processing, and functioning. A total of 20 studies met our inclusion/exclusion criteria. RESULTS: We found that functioning was significantly correlated with three domains of social cognition (ToM, emotion processing, and attribution bias). Twelve of 13 studies reported a correlation with emotion processing, but a correlation with ToM was only found in three of the 11 studies that assessed it. Six studies found an effect of depressive symptoms on emotion processing and no significant association was found with manic symptomatology. CONCLUSIONS: To the best of our knowledge, the present review is the first to specifically explore the relationship between social cognition and social functioning in patients with BD. This exploration is of interest, as it enhances current understanding of this disorder and, by so doing, should improve patient outcomes. PMID- 29787962 TI - Long term outcomes of acute and transient psychotic disorders: The missed opportunity of preventive interventions. AB - BACKGROUND: Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear. METHODS: Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1 st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals. RESULTS: A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83-17.47%), 28.41% at 2-year (95%CI 26.80-30.09%), 33.96% at 3-year (95% CI 32.25-35.75%), 36.85% at 4-year (95%CI 35.07-38.69%), 40.99% at 5-year (95% CI 39.12-42.92%), 42.58% at 6-year (95%CI 40.67-44.55%), 44.65% at 7-year (95% CI 42.66-46.69%), and 46.25% at 8 year (95% CI 44.17-48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09-38.27%). CONCLUSIONS: Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes. PMID- 29787963 TI - SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression. AB - BACKGROUND AND AIMS: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide dependent protein deacetylase. Recent studies have demonstrated that enhancing SIRT1 expression or activity may modulate cholesterol and lipid metabolism. However, pharmacological and molecular regulators for SIRT1 are scarce. Here, we aimed to find novel small molecule modulators of SIRT1 to regulate cholesterol and lipid metabolism. METHODS: A high-throughput screening assay was established to identify SIRT1 activators. Surface plasmon resonance and immunoprecipitation were performed to confirm the interaction of E1231 with SIRT1. Cholesterol assay was performed to demonstrate the in vitro effect of E1231. The in vivo effect of E1231 was evaluated in experimental models. RESULTS: E1231, a piperazine 1,4 diamide compound, was identified as a SIRT1 activator with EC50 value of 0.83 MUM. E1231 interacted with recombinant human SIRT1 protein and deacetylated liver X receptor-alpha (LXRalpha). E1231 increased ATP-binding cassette transporter A1 (ABCA1) expression in RAW 264.7 cells dependent on SIRT1 and LXRalpha. E1231 promoted cholesterol efflux and inhibited lipid accumulation in RAW 264.7 cells via SIRT1 and ABCA1. In the golden hamster hyperlipidemia model, E1231 treatment decreased total cholesterol and triglyceride levels in both serum and the liver, while increased cholesterol content in feces. Moreover, E1231 increased ABCA1 and SIRT1 protein expression in the liver. In ApoE-/- mice, E1231 treatment reduced atherosclerotic plaque development compared with untreated ApoE-/- mice. CONCLUSIONS: We identified a novel SIRT1 activator E1231 and elucidated its beneficial effects on lipid and cholesterol metabolism. Our study suggests that E1231 might be developed as a novel drug for treating atherosclerosis. PMID- 29787964 TI - Comparison of macro and micro Raman measurement for reliable quantitative analysis of pharmaceutical polymorphs. AB - This work reports on the use of micro- and macro-Raman measurements for quantification of mebendazole (MBZ) polymorphs A, B, and C in mixtures. Three Raman spectrophotometers were studied with a laser spot size of 3, 80 and 100 MUm and spectral resolutions of 3.9, 9 and 4 cm-1, respectively. The samples studied were ternary mixtures varying the MBZ polymorphs A and C from 0 to 100% and polymorph B from 0 to 30%. Partial Least Squares (PLS) regression models were developed using the pre-processing spectra (2nd derivative) of the ternary mixtures. The best performance was obtained when the macro-Raman configuration was applied, obtaining RMSEP values of 1.68%, 1.24% and 2.03% w/w for polymorphs A, B, and C, respectively. In general, micro-Raman presented worst results for MBZ polymorphs prediction because the spectra obtained with this configuration does not represent the bulk proportion of mixtures, which have different particle morphologies and sizes. In addition, the influence of these particle features on micro-Raman measurements was also studied. Finally, the results demonstrated that reliable analytical quantifying of MBZ polymorphs can be reached using a laser with wider area illuminated, thus enabling acquisition of more reproductive and representative spectra of the mixtures. PMID- 29787965 TI - Applications of various analytical techniques in quality control of pharmaceutical excipients. AB - Although excipients are pharmacologically inert substances, still they are integral and significant ingredients of a pharmaceutical formulation. Their amount and concentration level along with the active pharmaceutical ingredients is of utmost importance to decide the pharmacokinetics and stability of a dosage form. It is becoming progressively more important to illustrate the purity of excipients throughout the development and manufacture of pharmaceutical products as the safety and efficacy of the pharmaceutical formulation is largely affected by the quality of excipients. Therefore it is essential to analyze these excipients by suitable analytical technique before their incorporation into the formulations. In the present review authors have summarized the reported applications of various analytical techniques being used in excipients analysis. These include capillary electrophoresis, static headspace capillary gas chromatography, gel permeation chromatography/size exclusion chromatography, LC IR hyphenated technique and Near IR etc. Various parameters and conditions optimized are also described along with the techniques. PMID- 29787967 TI - Preparation of alginate fibers coagulated by calcium chloride or sulfuric acid: Application to the adsorption of Sr2. AB - The adsorption behavior of Sr2+ over alginate (Alg) fibers prepared by wet spinning was investigated. Different grades of sodium alginate (Alg-Na) were chosen. The Alg fibers were obtained by coagulation of 1% H2SO4 (Alg-acid) or 5% CaCl2 (Alg-Ca) solutions. In addition, the Sr2+ adsorption percentages of the spherical Alg-Ca beads with a 0.672-mm-diameter was 70.64% which was significantly lower than that Alg-Ca fibers (79.49%). These results suggested that the fibrous shape is more suitable than the spheres as an adsorbent from sea water. For Sr2+ adsorption capacities using different Alg fibers, the Alg-acid fibers obtained from 12% IL-2 and 8% I-2 grade solutions reached adsorption equilibrium at 99.88 and 99.27%, respectively, within 3 min. However, the Alg-Ca fiber obtained from 8% I-2 grade solution reached equilibrium at 80.01% within 30 min. Moreover, the Alg-acid fiber obtained from 8% I-2 grade solution adsorbed up to 34 mg/g of Sr2+ at an initial concentration of 1700 mg/L solutions. However, when Sr2+ co-existing cations (Ca2+, Na+, and mixtures of them) the adsorption capacity of the Alg-Ca fiber obtained from 8% I-2 grade solution slightly decreased since the egg-box structure of Alg-Ca fiber favored the selective Sr2+ adsorption and subsequent ion exchange with Ca2+. PMID- 29787966 TI - Injection drug use, HIV/HCV, and related services in nonurban areas of the United States: A systematic review. AB - BACKGROUND: Injection drug use (IDU) in nonurban areas of the United States is a growing public health concern, but there has been no comprehensive assessment of existing research on injection-related HIV and hepatitis C (HCV) in nonurban communities. We conducted a systematic review to assess the current literature and identify knowledge gaps. METHODS: We systematically searched six databases for relevant articles published between January 1990 and June 2016 and screened, extracted, and analyzed the resulting data. Studies were included if they reported original findings from the nonurban U.S. related to 1) IDU and its role in HIV/HCV transmission, and/or 2) HIV/HCV services for people who inject drugs (PWID). RESULTS: Of 2330 studies, 34 from 24 unique research projects in 17 states met inclusion criteria. Despite increasing HCV and high vulnerability to injection-related HIV outbreaks in nonurban areas, only three studies since 2010 recruited and tested PWID for HIV/HCV. Twelve reported on sharing injection equipment but used varying definitions of sharing, and only eight examined correlates of injection risk. Nine studies on syringe access suggest limited access through syringe exchange programs and pharmacies. Only two studies addressed HCV testing, none addressed HIV testing, and three examined behavioral or other interventions. CONCLUSIONS: Despite growing concern regarding nonurban IDU there are few studies of HIV/HCV and related services for PWID, and the existing literature covers a very limited geographical area. Current research provides minimal insights into any unique factors that influence injection risk and HIV/HCV service provision and utilization among nonurban PWID. PMID- 29787969 TI - Efficacy of batch mode rotary drum composter for management of aquatic weed (Hydrilla verticillata (L.f.) Royle). AB - Invasive aquatic weed management is one of the biggest challenges in the field of solid waste management. Eichhornia crassipes, Pistia stratiotes and Hydrilla verticillata (L.f.) Royle pose some of the world's most noted aquatic weed problems. Previously reported studies on management of H. verticillata, a submersed aquatic plant, have shown that temporary removal, chemical treatment or biological control methods each have advantages and disadvantages. Removal programs that propose to compost harvested H. verticillata biomass may provide a novel technique to manage this issue. However, the properties of such compost as an agriculture resource are unclear. This study presents the different mix proportions of H. verticillata, cow dung and sawdust used for the composting of 550 L rotary drum composter. This work characterizes the biological, physicochemical, and respirometry properties of the various mixes over a 20-day composting period. The results suggest that the biomass of H. verticillata can be beneficially utilized to produce stable compost for potential use in agricultural systems. PMID- 29787968 TI - Background concentrations and quality reference values for some potentially toxic elements in soils of Sao Paulo State, Brazil. AB - Quality reference values (QRV) for potentially toxic elements (PTE) in soils are established as a tool for prevention and monitoring of soil pollution. These values should be periodically revised in order to ensure soil safety for agricultural purposes. Brazil is market leader for several commodities; therefore, the safety of Brazilian soils is of worldwide strategic importance. The objective of this study was to determine the natural background concentrations and the QRV for As, Ba, Cd, Cr, Ni, Pb, Se, and Zn by investigating 30 representative pedotypes in the Sao Paulo State, one of the most important agro-industry economy at worldwide level. Multivariate statistical analysis was applied to determine the sources of PTE and their variability. The mean natural background concentrations of PTE in the soils were generally lower to those reported in literature. QRV, calculated for each element as the 75th and 90th percentiles, were lower (75th for As, Cd, Pb, and Zn), similar (75th for Ba, Cr, and Se) or above (90th for Ba, Cr, and Se and 75-90th for Ni) those previously proposed by the Brazilian environmental protection agencies. The results indicate that 75th percentile may be too restrictive. The PTE in the investigated soils appear to have comes mainly from two primary natural sources: a prevalent one of geogenic and a secondary of pedogenic origin. These results confirm the predominant natural source of selected PTE in the investigated soils, thus sustaining the possibility of using the data set to develop QRV for the State of Sao Paulo. PMID- 29787970 TI - Functional polyaniline/multiwalled carbon nanotube composite as an efficient adsorbent material for removing pharmaceuticals from aqueous media. AB - The composite polyaniline/multiwalled carbon nanotube (PAni/MWCNT, 1:0.1 w/w) was developed with the intention of binding the adsorbent properties of two materials and using it to adsorb pharmaceuticals from aqueous media. PAni/MWCNT was characterized by scanning electron microscopy, thermogravimetry, infrared spectroscopy, pH at the point of zero charge, and the effect on the surface wettability of the material. As proof of concept, adsorption studies were carried out using meloxicam (MLX) as the pharmaceutical and it was evaluated as a function of pH, temperature, ionic strength, contact time and variation in concentration. Kinetics and isothermal models were applied to evaluate the mechanism of the adsorption process. The best MLX adsorption result was at pH 2 with 6 min of contact with PAni/MWCNT. The kinetics models that fitted the experimental data were pseudo-second order and Elovich and the kinetics model was the dual-site Langmuir-Freundlich. Both models suggest that the adsorption occurs by the chemical nature of the surface and in the pores of the energetically heterogeneous composite. The PAni/MWCNT presented an adsorption capacity of 221.2 mg g-1, a very good value when compared with the literature and can be used to remove pharmaceuticals from aqueous environments. PMID- 29787972 TI - Investigation by direct-infusion ESI-MS and GC-MS of an alleged Leuckart route specific impurity of methamphetamine. AB - Impurity profiling has been used as a useful tool for analyzing nearly every drug class currently known on the illicit market. Impurities present within seized samples have the potential to determine source of origin, route of synthesis used, as well as provide a useful clue into the potential reaction mechanisms that are present for each synthetic procedure. Perhaps the most well studied of these impurity profiles exists for methamphetamine, including information to more than one route of synthesis. Within the present study, a complete synthesis of methamphetamine was performed, including a reductive amination of phenylpropanone (P2P) using methylamine hydrochloride and sodium triacetoxyborohydride (STAB) rather than the conventional aluminum mercury amalgam commonly found in the literature. During the analysis of the final product from this reaction, a major impurity within the reaction, bis(1-phenylpropan-2-yl)amine (m/z 253), was detected by GC-MS as well as direct-infusion ESI-MS. This impurity has been previously reported as a Leuckart route-specific impurity. Its detection within the reductive amination of P2P points towards the use of impure methylamine hydrochloride containing some traces of acid, and provides further insight into the reductive amination of P2P. In both the Leuckart reaction and this reductive amination via STAB, the presence of acid and ammonia leads to this impurity. PMID- 29787971 TI - Cellular mechanisms of physicochemical membrane homeostasis. AB - Biological membranes are vital, active contributors to cell function. In addition to specific interactions of individual lipid molecules and lateral organization produced by membrane domains, the bulk physicochemical properties of biological membranes broadly regulate protein structure and function. Therefore, these properties must be homeostatically maintained within a narrow range that is compatible with cellular physiology. Although such adaptiveness has been known for decades, recent observations have dramatically expanded its scope by showing the breadth of membrane properties that must be maintained, and revealing the remarkable diversity of biological membranes, both within and between cell types. Cells have developed a broad palette of sense-and-respond machineries to mediate physicochemical membrane homeostasis, and the molecular mechanisms of these are being discovered through combinations of cell biology, biophysical approaches, and computational modeling. PMID- 29787973 TI - Mitigation of algal organic matter released from Chaetoceros affinis and Hymenomonas by in situ generated ferrate. AB - This study demonstrates the application of in situ ferrate (Fe(VI)) for the efficient removal of dissolved algal organic matter (AOM) from seawater. Sodium hypochlorite (NaOCl) and ferric (Fe(III)) were used to produce in situ Fe(VI) by wet chemical oxidation. First, the removal efficiencies of two model AOM compounds, humic acid (HA) and sodium alginate (SA), were evaluated in the presence of sodium chloride with an initial influent dissolved organic carbon (DOC) concentration of 5.0 mg C L-1 at different pH levels to establish the optimal doses for in situ Fe(VI) generation. The concentration of Fe(VI) was determined by the 2,2-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) ultraviolet-visible spectrophotometry method. In the case of HA, 72% DOC removal was recorded when applied with 1.5 mg L-1 of Fe(III) and 1.5 mg L-1 of NaOCl (in situ Fe(VI) concentration of 1.46 mg L-1) while 42% DOC removal was observed for SA. Subsequently, the removal of AOM extracted from two bloom-forming algal species, Chaetoceros affinis (CA) and Hymenomonas (Hym), cultivated in seawater from the Red Sea, were tested with in situ generated Fe(VI) at the established optimum condition. In situ Fe(VI) recorded superior performance in removing AOM extracted from CA and Hym, showing 83% and 92% DOC removal when the influent DOC concentrations were 2.48 and 2.63 mg L-1, respectively. A detailed AOM characterization was conducted using liquid chromatography-organic carbon detection. PMID- 29787974 TI - Using big data from air quality monitors to evaluate indoor PM2.5 exposure in buildings: Case study in Beijing. AB - Due to time- and expense- consuming of conventional indoor PM2.5 (particulate matter with aerodynamic diameter of less than 2.5 MUm) sampling, the sample size in previous studies was generally small, which leaded to high heterogeneity in indoor PM2.5 exposure assessment. Based on 4403 indoor air monitors in Beijing, this study evaluated indoor PM2.5 exposure from 15th March 2016 to 14th March 2017. Indoor PM2.5 concentration in Beijing was estimated to be 38.6 +/- 18.4 MUg/m3. Specifically, the concentration in non-heating season was 34.9 +/- 15.8 MUg/m3, which was 24% lower than that in heating season (46.1 +/- 21.2 MUg/m3). A significant correlation between indoor and ambient PM2.5 (p < 0.05) was evident with an infiltration factor of 0.21, and the ambient PM2.5 contributed approximately 52% and 42% to indoor PM2.5 for non-heating and heating seasons, respectively. Meanwhile, the mean indoor/outdoor (I/O) ratio was estimated to be 0.73 +/- 0.54. Finally, the adjusted PM2.5 exposure level integrating the indoor and outdoor impact was calculated to be 46.8 +/- 27.4 MUg/m3, which was approximately 42% lower than estimation only relied on ambient PM2.5 concentration. This study is the first attempt to employ big data from commercial air monitors to evaluate indoor PM2.5 exposure and risk in Beijing, which may be instrumental to indoor PM2.5 pollution control. PMID- 29787975 TI - Rethink potential risks of toxic emissions from natural gas and oil mining. AB - Studies have showed the increasing environmental and public health risks of toxic emissions from natural gas and oil mining, which have become even worse as fracking is becoming a dominant approach in current natural gas extraction. However, governments and communities often overlook the serious air pollutants from oil and gas mining, which are often quantified lower than the significant levels of adverse health effects. Therefore, we are facing a challenging dilemma: how could we clearly understand the potential risks of air toxics from natural gas and oil mining. This short study aims at the design and application of simple and robust methods to enhance and improve current understanding of the becoming worse toxic air emissions from natural gas and oil mining as fracking is becoming the major approach. Two simple ratios, the min-to-national-average and the max-to national-average, are designed and applied to each type of air pollutants in a natural gas and oil mining region. The two ratios directly indicate how significantly high a type of air pollutant could be due to natural gas and oil mining by comparing it to the national average records, although it may not reach the significant risks of adverse health effects according to current risk screening methods. The min-to-national-average and the max-to-national-average ratios can be used as a direct and powerful method to describe the significance of air pollution by comparing it to the national average. The two ratios are easy to use for governments, stakeholders, and the public to pay enough attention on the air pollutants from natural gas and oil mining. The two ratios can also be thematically mapped at sampled sites for spatial monitoring, but spatial mitigation and analysis of environmental and health risks need other measurements of environmental and demographic characteristics across a natural gas and oil mining area. PMID- 29787976 TI - Opposite effects of mixtures of commercial formulations of glyphosate with auxinic herbicides on the ten spotted live-bearer fish Cnesterodon decemmaculatus (Pisces, Poeciliidae). AB - We analyzed the acute toxicity of the 48% glyphosate (GLY)-based Credit(r), the 57.71% dicamba (DIC)-based Kamba(r), and the 83.5% 2,4-dichlorophenoxyacetic acid (2,4-D)-based Weedar(r) Full, alone and as mixtures on the fish Cnesterodon decemmaculatus. Mortality revealed the LC50 96h values of 91.73 mg L-1 (range: 86.80-98.00 mg L-1), 1401.57 mg L-1 (range: 1243.78-1527.35) and 678.04 mg L-1 (range: 639.35-718.04 mg L-1) for GLY, DIC and 2,4-D, respectively. Mean values for the toxic unit (TU) that induced 50% mortality (TU50 96h) of fish exposed to equitoxic mixtures were 1.67 (range: 1.65-1.69) for Credit(r) and Kamba(r) and 1.28 (range: 1.20-1.36) for Credit(r) and Weedar(r) Full suggesting that both mixtures are antagonic. Non-equitoxic combinations demonstrated an antagonistic interaction of herbicides Credit(r) and Kamba(r), whereas a synergistic effect was observed for Credit(r) and Weedar(r) Full formulations. GLY and DIC as a mixture demonstrated lower toxicity on non-target species compared to GLY and 2,4 D in combination, at least for C. decemmaculatus, leading to the conclusion that the former combination could be strongly recommended in further agricultural practices. PMID- 29787977 TI - Pollution level and reusability of the waste soil generated from demolition of a rural railway. AB - Railways are typically considered polluted from years of train operation. However, the pollution level of railway in a rural area, which is less exposed to hazardous material from trains and freights, is rarely assessed. This study evaluated common railway pollutants such as heavy metals, total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs) and their chemical properties in the waste soil generated from the renovation of an old railway in rural area of Wonju, South Korea. Furthermore, lab-scale cultivation tests of peas (Pisum sativum) were performed to assess reusability of the waste soil as a soil amendment. Carbonaceous materials were found in the upper layer of the railway (0 to -40 cm) and the concentration of common railway pollutants was comparable to those of the agricultural land nearby. Specifically, total aromatic and aliphatic TPHs were below detection limit; and total PAHs < 1.0 mg kg-1 was 1000-times less than railway functional parts. Applying the carbonaceous waste soil improved the water holding capacity of soil by approximately 10% and sprouts formed on the soil with 10% waste soil composition had greater fresh weight, stem length, and root length than the control. Although this investigation was confined to a small length of the railway route, the results confirm environmental safety and the potential value of the waste generated from rural railways for the first time. PMID- 29787978 TI - Persistence of bacterial pathogens, antibiotic resistance genes, and enterococci in tidal creek tributaries. AB - Intertidal creeks form the primary hydrologic link between estuaries and land based activities on barrier islands. Fecal indicators Enterococcus spp. (Entero1), pathogens Shigella spp. (ipaH), Salmonella spp. (invA), E. coli of EHEC/EPEC groups (eaeA), E. coli of EAEC, EIEC, and UPEC groups (set1B), E. coli of STEC group (stx1); and tetracycline resistance genes (tet(B), tet(C), tet(D), tet(E), tet(K), tet(Q), tet(W), and tet(X); TRG) were detected in the headwater of Oakdale Creek (Sapelo Island, GA) receiving runoffs from Hog Hammock village. Excavation of drainage ditches around the village caused a high increase in the incidence of the above determinants. Water samples were collected from the headwater, transferred to diffusion chambers, submersed in the headwater, saltmarsh, and mouth of the creek; and the determinants were monitored for 3 winter months. With some exceptions, their persistence decreased in order headwater > saltmarsh > mouth. Genes associated with Enterococcus spp. were the most persistent at all the sites, following in the headwater with determinants for Salmonella spp. and E. coli of EAEC, EIEC, and UPEC groups. In the mouth, the most persistent gene was eaeA indicating EHEC, EPEC, and STEC. Tet(B) and tet(C) persisted the longest in headwater and saltmarsh. No TRG persisted after 11 days in the mouth. Most determinants revealed correlations with temperature and pH, and inverse correlations with dissolved oxygen. Decay rates of the above determinants varied in the range of -0.02 to -0.81/day, and were up to 40 folds higher in the saltmarsh and mouth than in the headwater. Our data demonstrated that water parameters could to some extent predict a general trend in the fate of virulence and antibiotic resistance determinants in tidal creek tributaries but strongly suggested that their persistence in these tributaries cannot be predicted from that of enterococci, or extrapolated from one biological contaminant to another. PMID- 29787979 TI - Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism. AB - The interplay between inflammation and metabolism is widely recognized, yet the underlying molecular mechanisms remain poorly characterized. Using experimental database mining and genome-wide gene expression profiling methods, we found that in contrast to other TNFAIP8 family members, TNFAIP8L2 (TIPE2) was preferentially expressed in human myeloid cell types. In addition, Tnfaip8l2 expression drastically decreased in lipopolysaccharide (LPS)-stimulated macrophages. Consequently, Tnfaip8l2 deficiency led to heightened expression of genes that were enriched for leukocyte activation and lipid biosynthesis pathways. Furthermore, mitochondrial respiration rate was increased in Tnfaip8l2-deficient macrophages, as measured by Seahorse metabolic analyzer. Taken together, these results indicate that Tnfaip8l2 serves as a "brake" for immunometabolism, which needs to be released for optimized metabolic reprogramming as well as mounting effective inflammatory responses. The unique anti-inflammatory and metabolic modulatory function of TNFAIP8L2 renders it a novel therapeutic target for cardiovascular diseases and cancer. PMID- 29787980 TI - Autophagy and MHC-restricted antigen presentation. AB - Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle trafficking, and autophagy, play critical roles in presentation of these antigens. We discuss the role of autophagy, a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. We propose the new term "Type 2 cross presentation" (CP2) to define the autophagy-dependent processes leading to MHC II restricted presentation of intracellular antigens by professional antigen presenting cells. A better understanding of Type 2 cross-presentation may guide future efforts to control the immune system through autophagy manipulation. PMID- 29787981 TI - Autologous bridging of rotator cuff tears with a hamstring tendon patch. A cadaver feasibility study and biomechanical testing. PMID- 29787983 TI - Circuit filling factor (CFF) for multiply tuned probes, revisited. AB - The concept of circuit filling factor (CFF) is re-examined for multi-tuned, multi inductor probe circuits. The CFF is the fraction of magnetic stored energy residing in the NMR coil. The CFF theorem states that the CFF sums to unity across all the resonant normal modes. It dictates that improved performance from a large CFF in one mode comes at the expense of CFF (and performance) at the other mode(s). Simple analytical calculations of two-mode circuits are used to demonstrate and confirm the CFF theorem. A triple-resonance circuit is calculated to show the large trade-offs involved there. The theorem can provide guidance for choosing the best circuit and relative inductances in multi-nuclear probes. The CFF is directly accessible from ball frequency-shift measurements. We give experimental measures of the CFF from ball shifts and compare to calculated values of the CFF, with good agreement. PMID- 29787982 TI - Neuroimaging findings of extensive sphenoethmoidal dysplasia in NF1. AB - Whereas isolated sphenoid wing dysplasia (SWD) is a well-known clinical feature in neurofibromatosis 1 (NF1), extensive cranial defects involving multiple bones have been rarely reported in this disorder. In this report, we describe the clinical course of a 20-year-old male with NF1 and an extensive cranial bone dysplasia. The large sphenoethmoidal defect was associated with transethmoidal and orbital cephalocele as well as inferolateral herniation of the frontal lobe. In spite of the large defect, the individual did not have any symptoms or complications resulting from the osteopathy. We review the current knowledge of the pathogenesis and management of cranial bone dysplasia in NF1. PMID- 29787985 TI - RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1. AB - This work aims to explore the roles and related mechanisms of RNA binding protein Lin28B in gastric cancer cells stemness. We found that Lin28B expression was negatively correlated with the overall survival (OS) of gastric cancer patients, and significantly increased in gastric cancer cells compared with that in gastric epithelial cells. Lin28B overexpression increased spheroid formation, expression of gastric cancer stemness-related markers, and decreased cisplatin sensitivity in gastric cancer cells. Mechanistically, Lin28B could directly bind to NRP-1 3'UTR, thus increasing NRP-1 mRNA stability and expression, and activate the downstream Wnt/beta-catenin signaling. Knockdown of NRP-1 or treatment with Wnt/beta-catenin antagonist could rescue the promotive effects of Lin28B on gastric cancer stemness. Thus, thes results indicate that Lin28B could facilitate gastric cancer stemness via directly binding to NRP-1 3'UTR and activating the downstream Wnt/beta-catenin signaling. PMID- 29787984 TI - Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years. AB - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. METHODS: We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 +/- 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. RESULTS: Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ?PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ?PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT3). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T4 (FT4) in males. Prenatal ?PBDEs were not associated with TT4, FT4, or total T3. CONCLUSIONS: These findings suggest an inverse relationship between prenatal ?PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males. PMID- 29787987 TI - Modulation of autophagy as new approach in mesenchymal stem cell-based therapy. AB - Due to their trophic and immunoregulatory characteristics mesenchymal stem cells (MSCs) have tremendous potential for use in a variety of clinical applications. Challenges in MSCs' clinical applications include low survival of transplanted cells and low grafting efficiency requiring use of a high number of MSCs to achieve therapeutic benefits. Accordingly, new approaches are urgently needed in order to overcome these limitations. Recent evidence indicates that modulation of autophagy in MSCs prior to their transplantation enhances survival and viability of engrafted MSCs and promotes their pro-angiogenic and immunomodulatory characteristics. Here, we review the current literature describing mechanisms by which modulation of autophagy strengthens pro-angiogenic and immunosuppressive characteristics of MSCs in animal models of multiple sclerosis, osteoporosis, diabetic limb ischemia, myocardial infarction, acute graft-versus-host disease, kidney and liver diseases. Obtained results suggest that modulation of autophagy in MSCs may represent a new therapeutic approach that could enhance efficacy of MSCs in the treatment of ischemic and autoimmune diseases. PMID- 29787986 TI - Anti-inflammatory effects and mechanism of the total flavonoids from Artemisia scoparia Waldst. et kit. in vitro and in vivo. AB - Artemisia scoparia Waldst. et Kit. is traditionally used for the treatment of jaundice urinary retention, itching wet sores, infectious icteric hepatitis and influenza in Uighur medicine. This study aimed to further illuminate the anti inflammatory effects and mechanism of the total flavonoids (ASTF) from Artemisia scoparia Waldst. et Kit. In vitro, RAW 264.7 cells were pretreated with ASTF 1 h before stimulation with LPS (1 MUg/mL) for 24 h. Then, the concentrations of NO, PGE2, TNF-alpha, IL-6 and MCP-1 in the medium were determined. Intracellular oxidative stress was detected using DCFH-DA. Immunofluorescent analysis, western blot and qRT-PCR were carried out to illuminate the mechanism of anti inflammatory effects of ASTF. In vivo, mice were given an intragastric administration of ASTF 1 h before an intranasal administration of LPS. After 24 h, bronchoalveolar lavage fluid (BALF) was collected to measure the number of total cells, macrophage and neutrophils. The levels of TNF-alpha and IL-6 in BALF were quantified by ELISA kits. Lung specimens were isolated for histopathological examinations and lung wet-to-dry weight (W/D) ratio. We found that ASTF significantly inhibited the production of NO, PGE2, TNF-alpha, IL-6, MCP-1 and reactive oxygen species (ROS) in LPS-stimulated RAW 264.7 cells. ASTF can obviously inhibit the degredation of IkappaBa and inhibit the nucleus translocations of p-NF-kappaB p65, p-ERK1/2 and p-p38 in RAW 264.7 cells stimulated by LPS. ASTF also markedly decreased the protein and mRNA expression of TNF-alpha and IL-6 in a dose-dependent manner. When pretreated with ASTF, alveolar hemorrhage and neutrophil infiltration, as well as pulmonary histopathologic changes, were substantially suppressed in lung tissues in the murine acute lung injury model. The lung wet-to-dry weight (W/D) ratio was strongly decreased. These results suggested that ASTF showed important anti inflammatory activity and might provide protective effects against LPS-induced ALI. The anti-inflammatory effect of ASTF might attribute to its suppression of NF-kappaB and MAPK signaling pathway. PMID- 29787988 TI - MicroRNA-30e promotes hepatocyte proliferation and inhibits apoptosis in cecal ligation and puncture-induced sepsis through the JAK/STAT signaling pathway by binding to FOSL2. AB - INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen 2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model. The hepatocytes were subject to miR-30e mimics, miR-30e inhibitors or siRNA-FOSL2. The expressions of miR-30e, FOSL2, apoptosis- and, JAK/STAT signaling pathway-related genes in liver tissues and hepatocytes were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. MTT assay and flow cytometry were performed to evaluate hepatocyte viability and apoptosis, respectively. RESULTS: The results obtained revealed that in the septic rats, serum levels of inflammatory factors, LPS, ALT and AST, as well as the expression of FOSL2 were elevated and the JAK/STAT signaling pathway was activated, while there was a reduction in the expression of miR-30e. An initial bioinformatics prediction followed by a confirmatory dual luciferase reporter assay determined that miR-30e targeted and negatively regulated FOSL2 expression. MiR-30e inhibited the activation of JSK2/STAT3 signaling pathway by reducing FOSL2 expression, while miR-30e enhanced hepatocyte proliferation and decreased hepatocyte cell apoptosis in septic rats. CONCLUSION: These findings indicated that miR-30e may serve as an independent therapeutic target for sepsis, due to its ability to inhibit apoptosis and induce proliferation of hepatocytes by targeted inhibition of FOSL2 through the JAK/STAT signaling pathway. PMID- 29787989 TI - Downregulation of microRNA-216b contributes to glioma cell growth and migration by promoting AEG-1-mediated signaling. AB - Accumulating evidence indicates microRNA-216b (miR-216b) plays an important role in the development and progression of various cancers. However, little is known about the function of miR-216b in gliomas. In this study, we aimed to investigate the expression level and functional significance of miR-216b in gliomas. We found that miR-216b was significantly downregulated in glioma specimens and cell lines. Overexpression of miR-216b suppressed the growth and migration of glioma cells, while miR-216b inhibition showed the opposite effects. Astrocyte elevated gene-1 (AEG-1) was predicted as a potential target gene of miR-216b by bioinformatics analysis. A dual-luciferase reporter assay showed that miR-216b could directly target the 3'-untranslated region of AEG-1. RT-qPCR and western blot analysis showed that miR-216 negatively regulated AEG-1 expression in glioma cells. Correlation analysis revealed an inverse correlation between miR-216b and AEG-1 in clinical glioma specimens. miR-216b also regulated the activation of nuclear factor-kappaB and Wnt signaling in glioma cells. Moreover, restoration of AEG-1 expression partially reversed the inhibitory effect of miR-216b overexpression on glioma cell growth and migration. Overall, these results revealed a tumor suppressive role of miR-216b in glioma tumorigenesis, and identified AEG-1 as a target gene of miR-216b action. Our study suggests that miR-216b can be potentially targeted for the development of novel therapies for gliomas. PMID- 29787991 TI - Synthetic chalcones as potential tool for acute- and chronic-pain control. AB - The purpose of this study was to validate the potential anti-hypersensitive activity of two chalcones, (2E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1 one (ANCh) and N-{4-[(2E)-3-(4-nitrophenyl)prop-2-enoil]phenyl}acetamide (AcANCh), by different models of acute and persistent pain in mice, besides in silico analysis. Molecules computational investigation for prediction of Lipinki's and Veber's rules to determine solubility, % absorption, drug likeness and toxicity liabilities was performed. Male and female C57BL/6 mice (20-30 g, n = 6) were used. Firstly, mice were pre-treated with the compounds ANCh or AcANCh and then submitted to the models of acute hypersensitivity by the intraplantar injection of different phlogistic agents. The mechanical sensitivity was assessed using von Frey hairs (0.6 g). The obtained data shows that both compounds presented important inhibitory effects on mechanical hypersensitivity induced by carrageenan (with oral bioavailability). The anti-hypersensitive effect was also accompanied by the interference in leukocyte migration, interleukin-1beta (IL 1beta) and tumour necrosis factor (TNF) levels reduction and by the absence of unspecific effects. Added to the in vivo results, the in silico analysis presented none violation in Lipinski's or Veber's rules, good probability to cell membrane permeability and oral bioavailability, positive values of drug likeness and few risk of computational toxicity. ANCh partially reduced the hypersensitivity induced by IL-1beta and TNF, epinephrine and prostaglandin E2 (PGE2). AcANCh had similar effect, except for the absent of inhibition in PGE2 injected mice. Both compounds were capable of reducing the mechanical hypersensitivity presented in all persistent models of hypersensitivity (inflammatory pain, chronic nerve constriction and cancer pain), with emphasis for ANCh. These results suggest that both chalcones could represent good strategies for the control of acute and chronic pain, without important side effects. ANCh seems to involve cell migration and cytokines production as the main mechanism, together with interference in PGE2 neuronal sensitization pathway. In vivo and in silico analyses reinforce the potential characteristics of the compounds to become future drugs. PMID- 29787990 TI - Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice. AB - AIMS: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl4-induced ALI. MAIN METHODS: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl4 administration. Sham and ovx mice were given DMTU, Melo or saline intraperitoneally 30 min before CCl4 or corn oil administration. KEY FINDINGS: ALT levels in ovx mice were significantly increased compared to those in sham mice. DMTU reduced ALT levels in ovx mice to the same levels as those in sham mice after CCl4 injection. CCl4 upregulated TNF-alpha, IL 6, cox-2 and iNOS expression in ovx mice compared to the levels in sham mice. DMTU significantly reduced cox-2 and iNOS expression levels upregulated by CCl4 in ovx mice. However, pretreatment with Melo had no effects on ALT levels and the gene expression levels of TNF-alpha, IL-6 and HO-1 in either sham or ovx mice, indicating that cox-2 may not participate in increase of CCl4-induced ALI caused by estrogen deficiency. SIGNIFICANCE: Ovariectomy accelerated the development of CCl4-induced acute liver injury, and DMTU reduced liver injury. These results suggest that estrogen may act as an antioxidant in the development CCl4-induced acute liver injury. PMID- 29787992 TI - Reliability and validity analysis of the open-source Chinese Foot and Ankle Outcome Score (FAOS). AB - AIM: Develop the first reliable and validated open-source outcome scoring system in the Chinese language for foot and ankle problems. METHODS: Translation of the English FAOS into Chinese following regular protocols. First, two forward translations were created separately, these were then combined into a preliminary version by an expert committee, and was subsequently back-translated into English. The process was repeated until the original and back translations were congruent. This version was then field tested on actual patients who provided feedback for modification. The final Chinese FAOS version was then tested for reliability and validity. Reliability analysis was performed on 20 subjects while validity analysis was performed on 50 subjects. Tools used to validate the Chinese FAOS were the SF36 and Pain Numeric Rating Scale (NRS). Internal consistency between the FAOS subgroups was measured using Cronbach's alpha. Spearman's correlation was calculated between each subgroup in the FAOS, SF36 and NRS. RESULTS: The Chinese FAOS passed both reliability and validity testing; meaning it is reliable, internally consistent and correlates positively with the SF36 and the NRS. DISCUSSION AND CONCLUSIONS: The Chinese FAOS is a free, open source scoring system that can be used to provide a relatively standardised outcome measure for foot and ankle studies. PMID- 29787993 TI - Systematic screening and characterization of Qi-Li-Qiang-Xin capsule-related xenobiotics in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. AB - Qi-Li-Qiang-Xin capsule (QLQX), a well-known traditional Chinese medicine prescription (TCMP), is consisted of eleven commonly used herbal medicines, has been widely used for the treatment of chronic heart failure (CHF). However, the absorbed components and related metabolites after oral administration of QLQX are still remaining unknown. In the present work, a reliable and effective method using ultra performance liquid chromatography coupled with quadrupole time-of flight tandem mass spectrometry (UPLC/Q-TOF-MS) was established to identify QLQX related xenobiotics in rats. Based on a representative structure based homologous xenobiotics identification (RSBHXI) strategy, a total of eleven compounds (salvianolic acid B, formononetin, benzoylmesaconine, alisol A, sinapine thiocyanate, naringin, tanshinone IIA, ginsenoside Rg1, ginsenoside Rb1, astragaloside IV and periplocin), bearing different chemical core structures, were selected and investigated for their metabolism in vivo. And then, comprehensive metabolic profiles of the holistic multi-ingredients in QLQX were achieved. As a result, a total of 121 QLQX-related xenobiotics (47 prototypes and 74 metabolites) were identified or tentatively characterized, among them eight prototypes (mesaconine, hypaconine, songorine, fuziline, neoline, talatizamine formononetin, neocryptotanshinone) and two metabolites (calycosin-gluA, formononetin-guA) were relatively the main existing xenobiotics exposed in blood. All absorbed prototype constituents were mainly from six composed herbal medicines (Aconiti lateralis radix, Astragali radix, Ginseng radix, Alismatis rhizoma, Salvia miltiorrhiza radix, Periploca cortex). The main metabolic reactions were methylation, hydrogenation, hydroxylation, oxidization, sulfation and glucuronidation. This is the first study on in vivo metabolism of QLQX. These results enabled us to focus on several high exposure ingredients in the discovery of effective substances of QLQX, however further pharmacokinetic study on these QLQX-related xenobiotics are needed to be carried out. PMID- 29787995 TI - N-Point Moving Average: A Special Generalized Transfer Function Method for Estimation of Central Aortic Blood Pressure. AB - OBJECTIVE: N-point moving average (NPMA) is a simplified method of central aortic systolic pressure (CASP) estimation in comparison with the generalized transfer function (GTF). The fundamental difference or similarity between the methods is not established. This study investigates theoretical properties of NPMA relative to GTF and explores the integer and fractional denominator for the averaging process in the NPMA. METHODS: Convolution of a specified square wave and the radial (or brachial) blood pressure waveform constituted the NPMA . A single uniform tube model-based TF (MTF) was employed to investigate potential physiological meaning of NPMA. In experimental analysis, invasive, simultaneously recorded aortic and radial pressure waveforms were obtained in 62 subjects under control conditions and following nitroglycerin administration. CASP was estimated by NPMA (), GTF ( ), and MTF (CASP MTF) from radial waveforms by tenfold cross validation. RESULTS: Theoretical analysis showed that NPMA was an inversed constant TF. Its spectrum matched that of MTF in low frequency (<4 Hz for radial and <5 Hz for brachial) by optimizing reflection coefficient and propagation time. Experiment results showed the NPMA optimized fractional denominator of K = 4.4 significantly decreased the mean difference between CASPNPMA and measured CASP to 0.0 +/- 4.7 mmHg from -1.8 +/- 4.6 mmHg for integer denominator of K = 4. CASPNPMA correlated with CASPMTF and CASP GTF (r2 = 0.99 and 0.97, mean difference: -0.3 +/- 1.8 and 0.5 +/- 2.7 mmHg). CONCLUSION: This study demonstrated that NPMA is similar in nature to the GTF. PMID- 29787994 TI - Bioavailability of wilforlide A in mice and its concentration determination using an HPLC-APCI-MS/MS method. AB - Wilforlide A (WA), an active compound in Tripterygium wilfordii Hook F (TW) which is a traditional Chinese medicine for treatment of autoimmune diseases, is a quality control marker for TW product. At present, the bioavailability/pharmacokinetics of WA is not known. Such information is not only essential to evaluate the relevance of WA as a quality control maker, but also important for future clinical efficacy studies. Therefore, a high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometric method (HPLC-APCI-MS/MS) was developed and applied to a bioavailability/pharmacokinetic study of WA. WA and celastrol (the internal standard, IS) were extracted by a liquid-liquid extraction method using methyl tert-butyl ether. Multiple reaction monitoring (MRM) scanning in positive ionization mode was used to monitor the transition of m/z 455.1 to 191.3 for WA and 451.3 to 201.2 for IS. This method was validated and applied to a pharmacokinetic study of WA in mice following intravenous administration (IV, 1.2 mg/kg), intraperitoneal injection (IP, 6 mg/kg) and oral administration (PO, 30 mg/kg). The lower limit of quantification (LLOQ) for WA was 10 ng/ml. The intra- and inter-day precision was found to be within 15.4% while the accuracy within 94.1-115.7% for all the quality control and LLOQ samples. The samples were stable under all the usual storage and experimental conditions. The terminal elimination half-lives were 14.7, 9.1 and 22.7 min following IV, IP and PO dosing, while the absolute bioavailability for IP and PO WA were 9.39% and 0.58% respectively. These results indicated that the HPLC-APCI-MS/MS assay was suitable for the pharmacokinetic study of WA. WA was found poorly absorbed when given orally and therefore it may not be a relevant marker for the oral TW products in the market. PMID- 29787996 TI - Three-Dimensional Weighting in Cone Beam FBP Reconstruction and Its Transformation Over Geometries. AB - GOALS: With substantially increased number of detector rows in multidetector CT (MDCT), axial scan with projection data acquired along a circular source trajectory has become the method-of-choice in increasing clinical applications. Recognizing the practical relevance of image reconstruction directly from the projection data acquired in the native cone beam (CB) geometry, especially in scenarios wherein the most achievable in-plane resolution is desirable, we present a three-dimensional (3-D) weighted CB-FBP algorithm in such geometry in this paper. METHODS: We start the algorithm's derivation in the cone-parallel geometry. Via changing of variables, taking the Jacobian into account and making heuristic and empirical assumptions, we arrive at the formulas for 3-D weighted image reconstruction in the native CB geometry. RESULTS: Using the projection data simulated by computer and acquired by an MDCT scanner, we evaluate and verify performance of the proposed algorithm for image reconstruction directly from projection data acquired in the native CB geometry. CONCLUSION: The preliminary data show that the proposed algorithm performs as well as the 3-D weighted CB-FBP algorithm in the cone-parallel geometry. SIGNIFICANCE: The proposed algorithm is anticipated to find its utility in extensive clinical and preclinical applications wherein the reconstruction of images in the native CB geometry, i.e., the geometry for data acquisition, is of relevance. PMID- 29787997 TI - Depth-Based Whole Body Photoplethysmography in Remote Pulmonary Function Testing. AB - OBJECTIVE: We propose a novel depth-based photoplethysmography (dPPG) approach to reduce motion artifacts in respiratory volume-time data and improve the accuracy of remote pulmonary function testing (PFT) measures. METHOD: Following spatial and temporal calibration of two opposing RGB-D sensors, a dynamic three dimensional model of the subject performing PFT is reconstructed and used to decouple trunk movements from respiratory motions. Depth-based volume-time data is then retrieved, calibrated, and used to compute 11 clinical PFT measures for forced vital capacity and slow vital capacity spirometry tests. RESULTS: A dataset of 35 subjects (298 sequences) was collected and used to evaluate the proposed dPPG method by comparing depth-based PFT measures to the measures provided by a spirometer. Other comparative experiments between the dPPG and the single Kinect approach, such as Bland-Altman analysis, similarity measures performance, intra-subject error analysis, and statistical analysis of tidal volume and main effort scaling factors, all show the superior accuracy of the dPPG approach. CONCLUSION: We introduce a depth-based whole body photoplethysmography approach, which reduces motion artifacts in depth-based volume-time data and highly improves the accuracy of depth-based computed measures. SIGNIFICANCE: The proposed dPPG method remarkably drops the error mean and standard deviation of FEF , FEF , FEF, IC , and ERV measures by half, compared to the single Kinect approach. These significant improvements establish the potential for unconstrained remote respiratory monitoring and diagnosis. PMID- 29787999 TI - Cell intrinsic Wnt/beta-catenin signaling activation. PMID- 29787998 TI - Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice. AB - Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging. PMID- 29788000 TI - Building lipids for myelin. PMID- 29788001 TI - TORC1, stress and the nucleolus. PMID- 29788002 TI - Intraindividual Variation of Meiotic Recombination Parameters in Pig Spermatocytes: A Preliminary Study. AB - Meiotic recombination parameters like crossover (CO) rate or synaptonemal complex (SC) length are known to vary strongly between individuals and between cells from the same individual. The origins of this variability remain elusive, and little is known about the variations that might occur between different samples and/or over time within the same individual. To document this question, pachytene cells from 3 boars of the Large White breed were analyzed twice, at a 1-year interval, using immunocytological techniques. CO rate, SC length, and MLH1 inter-foci distances varied significantly between the 3 individuals. CO rate and SC length differed significantly between the 2 sampling periods for 1 individual. However, no significant differences were observed between the 2 samples for CO distribution and inter-foci distances in the 3 boars studied. PMID- 29788003 TI - Robotic Parathyroid Surgery: Current Perspectives and Future Considerations. AB - Robotic parathyroidectomy represents a novel surgical approach in the treatment of primary hyperparathyroidism when the parathyroid adenoma has been pre operatively localised. It represents the "fourth generation" in the evolution of parathyroid surgery following a process of surgical evolution from cervicotomy and 4-gland exploration to a variety of minimally invasive, open and endoscopic, targeted approaches. The existing evidence (levels 2-3) supports it as a feasible and safe technique with equivalent results to targeted open parathyroidectomy for primary hyperparathyroidism in carefully selected patients. However, it takes longer to perform and is more costly than conventional parathyroidectomy. It offers superior cosmesis by completely avoiding a neck scar making it a valid option for those patients who for biological and/or cultural reasons may wish to avoid a neck scar. Robotic parathyroidectomy is not for every patient, surgeon, or hospital. Its application should be confined to high-volume centres and experienced surgeons. Intensive training and proctorship are required for its safe implementation combined with careful patient selection. This particularly relates to the patient's body habitus (BMI < 30 kg/m2) and concordance among the different imaging modalities used pre-operatively. With robotic market competition driving down costs, its role may change. For now, robotic parathyroidectomy occupies a niche role and can only be justified in a select subset of patients. PMID- 29788004 TI - Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy. AB - The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF) 1alpha was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1alpha was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3beta (GSK-3beta), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury. PMID- 29788005 TI - Morphological Identification of Hair Recovered from Feces for Detection of Cannibalism in Eastern Chimpanzees. AB - Chimpanzees (Pan troglodytes) are primarily frugivorous but consume a variable amount of meat from a variety of organisms, including other chimpanzees. Cannibalism is rare, usually follows lethal aggression, and does not occur following natural deaths. While chimpanzee cannibalism has been documented at multiple sites, many instances of this behavior go unrecorded. Identification of chimpanzee remains in feces, however, can provide indirect evidence of cannibalism. Hair, in particular, typically passes through the gastrointestinal tract undamaged and is commonly used for purposes of identification in wildlife forensics. Here we test the hypothesis that eastern chimpanzee (Pan troglodytes schweinfurthii) guard hair morphology can be reliably distinguished from the hairs of their most common prey species. Methods and results are presented in the context of a case study involving a suspected chimpanzee infanticide from Gombe, Tanzania. We find that chimpanzee guard hair morphology is unique among tested mammals and that the presence of abundant chimpanzee hair in feces is likely the result of cannibalism and not incidental ingestion from grooming or other means. Accordingly, morphological analysis of guard hairs from feces is a promising, cost-effective tool for the determination of cannibalistic acts in chimpanzees. PMID- 29788006 TI - Peripheral Microvascular Abnormalities Detected by Wide-Field Fluorescein Angiography in Eyes with Branch Retinal Vein Occlusion. AB - PURPOSE: To evaluate the location of microvascular abnormalities using wide-field fluorescein angiography (WFFA) and investigate the impact on visual outcome in eyes with branch retinal vein occlusion (BRVO). METHODS: Forty eyes of 39 patients (24 males and 15 females with an average age of 71 years) were retrospectively reviewed. One patient had BRVO bilaterally. WFFA was performed in all patients to evaluate perfusion status and detect microvascular abnormalities. The WFFA images were divided into 3 zones: zone 1, posterior pole; zone 2, mid periphery; zone 3, far periphery, in order to document the presence of microvascular abnormalities. Scatter retinal photocoagulation (PC) was performed for retinal neovascularization (NV) and/or widespread nonperfused areas (NPAs). RESULTS: The incidence of microvascular abnormalities in zone 3 was significantly (p < 0.0001) less than in zones 1 and 2. The presence of larger NPAs in zone 1, but not in zone 3, was associated with the incidence of NV and vitreous hemorrhage. The presence of peripheral lesions and the application of PC did not affect the visual outcome. CONCLUSION: The presence of peripheral abnormalities or scatter PC for NPAs did not affect the visual outcome in eyes with BRVO. PMID- 29788008 TI - What Is New about New Antidepressants? PMID- 29788007 TI - Knowledge about Stroke in Belo Horizonte, Brazil: A Community-Based Study Using an Innovative Video Approach. AB - BACKGROUND AND PURPOSE: Stroke is a leading cause of death in Brazil. Knowledge about the clinical manifestations of stroke as well as its risk factors and its management is still poor in the country. We intended to assess the stroke knowledge of an urban population in Belo Ho-rizonte, Brazil. METHODS: Individuals assisted by a basic health unit were interviewed between February and August 2014. After demographic data collection, the participants were asked to watch a video that consisted of a person presenting stroke signals and they were asked to answer questions about the condition shown on the video. Afterwards, they answered a semi-structured questionnaire to evaluate their stroke knowledge. RESULTS: A total of 703 people were interviewed (62.1% female, mean age 46.7 years). Recognition of a person having a stroke on the presented video was achieved by 56.1% of the subjects. Female sex (p = 0.029) and contact with someone who had had a stroke (family member [p < 0.01], neighbor [p < 0.05]) increased the odds of correctly identifying the condition showed on the video. The most commonly mentioned clinical manifestations of stroke were weakness (34.7%) and speech disturbance (31.6%). Stroke risk factors that were most named were "unbalanced diet" (42.3%) and hypertension (33.7%). Most participants (66.8%) said they would call the emergency medical services, while 17.8% would go directly to a hospital. Only 17 subjects knew thrombolytic therapy for acute stroke. CONCLUSION: Female sex and a family history of stroke increased the odds of recognizing the signs of stroke. Knowledge about the clinical manifestations, risk factors, and management of stroke was low in the studied population. PMID- 29788009 TI - The Effect of Feeding Behavior on Hypothalamus in Obese Type 2 Diabetic Rats with Glucagon-like Peptide-1 Receptor Agonist Intervention. AB - OBJECTIVE: To investigate the utility of intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters in hypothalamus for monitoring the effect of Exendin-4 (Ex-4) intervention on the feeding behavior in obese diabetic rats within early feeding. METHODS: 21 obese and 19 non-obese rats which were treated with streptozotocin injections were initially divided into an obese diabetes group (OD, n = 10), a non-obese diabetes group (D, n = 8), an obese group (O, n = 9) and a non-obese group (N, n = 9). Then, the rats in the 4 groups received subcutaneous injections of Ex-4, and feeding behavior was examined at 5, 35, 65, 95, and 125 min. The hypothalamic function was evaluated by IVIM-DWI. Finally, the relationship between the hypothalamic function and the amount of food intake was analyzed. RESULTS: In comparison with the N group, the food intake significantly decreased in the O , OD, and D groups in response to Ex-4. Furthermore, a significant positive correlation was found between food intake and D values at different times from 5 to 125 min after Ex-4 intervention in all 4 groups. CONCLUSION: A direct correlation between the change of hypothalamic function and feeding behavior was detected in OD rats with Ex-4 intervention in the early feeding period. The hypothalamic D value derived from IVIM-DWI is promising to reflect the dynamic change of hypothalamic function due to intervention. PMID- 29788010 TI - Metaplastic Breast Cancer Masquerading as Liposarcoma of the Breast: A Case Report following Oncoplastic Treatment. AB - Mammary liposarcoma is among the rarest of breast tumours. Here we report the presentation, macroscopic, microscopic, and immunohistochemical features of an extremely rare case of metaplastic carcinoma with extensive pleomorphic liposarcomatous differentiation. A 47-year-old woman presented with bilateral grade III breast ptosis and a 3 * 4 cm mass in the lower outer quadrant of the left breast. Mammography and ultrasound confirmed a well-defined mass. A core biopsy performed was diagnosed as pleomorphic liposarcoma. Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses. Atypical lipoblasts were easily identifiable. Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made. Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ, and/or epithelial differentiation, and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis. PMID- 29788011 TI - Knowledge about Positive Premenstrual Changes and Somatosensory Amplification Increase the Report of Positive Premenstrual Changes: An Experimental Study. PMID- 29788012 TI - Allograft Inflammatory Factor-1 Mediates Macrophage-Induced Impairment of Insulin Signaling in Adipocytes. AB - BACKGROUND/AIMS: Allograft inflammatory factor-1 (AIF-1) is an inflammatory cytokine produced mainly by macrophages within human white adipose tissue. Its expression is increased in obese subjects and positively correlated with insulin resistance. The purpose of this study is to characterize the regulatory role of AIF-1 in insulin signaling of adipocyte. METHODS: AIF-1 was over-expressed via transfection of AIF-1 cDNA into murine RAW 264.7 macrophages, and the constitutive expression of AIF-1 was decreased via transfection of targeting siRNA. Murine 3T3L1 adipocytes were treated with macrophage-conditioned medium or AIF-1 protein. Intracellular lipid accumulation was assayed by oil red O stain. Reactive oxygen species production was determinated by a flow cytometer and adipokine secretion was measured with ELISA. Glucose uptake was detected using the glucose oxidase method and insulin-signal-transduction related molecules were analyzed by Western blot. RESULTS: Short term (48 h) AIF-1 treatment slightly promoted intracellular lipid storage in differentiating 3T3L1 cells. The protein stimulated reactive oxygen species production, provoked TNFalpha, IL6, resistin, but suppressed adiponectin release and insulin-stimulated glucose uptake both under normal basal and insulin resistance conditions. Furthermore, AIF-1 induced NF-kappaB activation, inhibited PPARgamma expression, GLUT4 translocation to plasma membrane and Akt phosphorylation. CONCLUSION: Macrophage-derived AIF-1 up regulated reactive oxygen species production, adipokine TNFalpha, IL6, resistin release, and inhibited adiponectin secretion. Moreover, it suppressed insulin stimulated glucose uptake by down-regulating insulin signaling. Thus, AIF-1 could be related to obesity-related diseases. PMID- 29788014 TI - Persistently Increased Resting Energy Expenditure Predicts Short-Term Mortality in Patients with Acute-on-Chronic Liver Failure. AB - OBJECTIVE: Hypermetabolism based on measurements of resting energy expenditure (REE) is suggested to be a potential biomarker for predicting the clinical outcomes of some diseases. We aimed to evaluate the potential value of hypermetabolism for predicting the short-term (28-day) mortality of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: A total of 105 HBV-ACLF patients, 30 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs) were included in this study. The REE was measured using indirect calorimetry in the morning after 8-10 h of fasting. The predicted REE (REEHB) was determined using Harris-Benedict equation. Persistent hypermetabolism was defined as the REE:REEHB ratio > 1.20 at day 1 and day 7 after admission. The severity of liver disease was estimated using the Model for End-Stage Liver Disease (MELD). Clinical and biochemical variables were determined using blood samples ordered upon admission. These variables were compared between nonsurviving and surviving patients who were classified according to the 28-day mortality. RESULTS: The frequency of hypermetabolism at baseline was significantly higher in ACLF patients than that in HCs and CHB patients. Forty six (43.8%) ACLF patients died within follow-up of 28 days. Persistent hypermetabolism (OR 2.10; 95% CI 1.15-3.69; p = 0.002) and MELD score (OR 1.93; 95% CI 1.47-3.51; p = 0.012) were independent predictive indicators of 28-day mortality. Furthermore, the performance of the 2 variables (persistent hypermetabolism and MELD) together with the area under the receiver operating curve (AUROC: 0.819) was significantly better than that of MELD alone -(AUROC: 0.694) for prediction of short-term mortality (p = 0.014). CONCLUSION: These findings indicate that persistent hypermetabolism is predictive of short-term mortality in this small population. PMID- 29788013 TI - Cerebrospinal Fluid BACE1 Activity and sAbetaPPbeta as Biomarker Candidates of Alzheimer's Disease. AB - BACKGROUND/AIMS: The utility of beta-site amyloid-beta precursor protein (AbetaPP) cleaving enzyme 1 (BACE1) activity and soluble AbetaPP beta (sAbetaPPbeta) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. METHODS: BACE1 activity and sAbetaPPbeta concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAbetaPPbeta to correct diagnostic classification to that of FDG PET. RESULTS: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAbetaPPbeta did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. CONCLUSIONS: Further studies using biomarker underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI. PMID- 29788015 TI - Limb-Bud and Heart Attenuates Growth and Invasion of Human Lung Adenocarcinoma Cells and Predicts Survival Outcome. AB - BACKGROUND/AIMS: The transcription cofactor limb-bud and heart (LBH) is involved in embryonic development. However, its role in human lung cancer, especially lung adenocarcinoma (LUAD), remains unclear. METHODS: A public database and tissue microarray (TMA) were used to compare differences in LBH expression and its relationship with clinical characteristics. Tissue from an additional 70 LUAD patients with follow-up records was used to explore the correlation of LBH expression with prognosis. Cellular and molecular studies validated the role of LBH in LUAD growth and invasion. RESULTS: LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients based on a public database and TMA. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). Cox regression analysis showed that LBH expression status was a favorable independent prognostic factor (hazard ratio = 0.120, 95% confidence interval = 0.016-0.894, P = 0.039). LBH knockdown accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analysis indicated that LBH was significantly related to the cell adhesion pathway. Western blot analysis confirmed that LBH could regulate the expression of integrin family members (integrin-alpha1, integrin-alpha2, integrin alpha4, integrin-alphav, and integrin-beta4). CONCLUSION: Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD and can attenuate cell growth and invasion. LBH may be a potential prognostic biomarker in LUAD patients. PMID- 29788017 TI - The Effect of Hidden Female Smoking on the Association between Smoking and Asthma. AB - BACKGROUND: The association between smoking and asthma remains controversial. In our previous study, we were not able to show an association between asthma and smoking in Korean adults. One Korean study demonstrated underreporting of smoking history by female adults. The aim of the present study was to investigate the effects of hidden female smoking on the association between asthma and smoking in Korean adults. METHODS: Data were acquired from 23,483 men and women aged >=19 years who participated in the Korean National Health and Nutrition Examination Surveys (KNHANES). RESULTS: The prevalence of asthma was 1.5%, the self-reported smoking prevalence was 32.4%, and the cotinine-verified smoking prevalence was 30.3%. Of the male cotinine-verified smokers, 6.4% were self-reported nonsmokers (2.7% never smokers and 3.7% ex-smokers), whereas 48.8% of the female cotinine verified smokers were self-reported nonsmokers (43.2% never smokers and 5.6% ex smokers). In males, the adjusted odds ratio of the association between smoking and asthma was 0.738 (confidence interval, CI: 0.393-1.173) in self-reported and 0.767 (CI: 0.515-1.143) in cotinine-verified smoking; in females, the adjusted odds ratio was 1.945 (CI: 1.348-2.805) in self-reported and 1.531 (CI: 1.076 2.179) in cotinine-verified smoking. CONCLUSIONS: Our study showed smoking was associated with asthma in females but not in males. PMID- 29788016 TI - Aedes communis Reactivity Is Associated with Bee Venom Hypersensitivity: An in vitro and in vivo Study. AB - Mosquito bite is usually followed by a local reaction, but severe or systemic reaction may, in rare cases, occur. Allergic reactions to Aedes communis (Ac) may be underestimated due to the lack of reliable diagnostic tools. In this multicenter study, 205 individuals reporting large local reactions to Ac were enrolled and studied for cutaneous or IgE reactivity to Ac, Blattella germanica, Penaeus monodon, and Dermatophagoides pteronyssinus. Extract and molecular IgE reactivity to bees, wasps, hornets, and yellow jacket venoms were also studied in 119 patients with a clinical history of adverse reaction to Hymenoptera. Immunoblot (IB) analysis and immunoCAP IgE inhibition experiments were carried out in selected sera. Ac sensitization was recorded in 96 (46.8%) patients on SPT. Strict relationship between Ac and D. pteronyssinus, B. germanica, P. monodon, or Apis mellifera reactivity on SPT was observed. Ac IgE recognition was seen in 60/131 (45.8%) patients, 49 (81.6%) of them SPT positive, and 5/14 IB reactors. Ac IgE sensitization was associated with Tabanus spp, A. mellifera, Vespula vulgaris, and Polistes dominula reactivity. A strict relationship between Ac IgE reactivity and Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was recorded. IgE reactivity to AC was inhibited in 9/15 cases after serum absorption with the A. mellifera extract. Both SPT and IgE Ac reactivity is observed in about half of patients with a history of large local reactions to mosquito bites. The significant relationship between Ac sensitization and either extract or single bee venom components is suggestive of a "bee-mosquito syndrome" occurrence. PMID- 29788018 TI - Brain Immunohistopathology in a Patient with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy. AB - BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel meningoencephalomyelitis. However, the pathogenesis of this disease is unclear. We therefore examined a brain biopsy from a patient with autoimmune GFAP astrocytopathy by immunohistopathology. METHODS: We examined brain biopsy sections from a patient with autoimmune GFAP astrocytopathy using hematoxylin and eosin (HE) and Luxol fast blue (LFB) staining, and immunostaining with antibodies for CD4, CD8, CD3, CD20, CD68, CD138, Neu-N, GFAP, myelin oligodendrocyte glycoprotein (MOG), and aquaporin-4 (AQP4). RESULTS: HE staining revealed extensive inflammatory cells (marked lymphocytes) around brain vessels, and LFB showed no signs of demyelination or axon loss. Immunohistochemical analysis showed CD3+ and CD4+ T cells cuffing around brain vessels, accompanied by CD8+ T cells, CD20+ B cells, and CD138+ plasma cells, while some macrophages (CD68+) were scattered throughout the brain parenchyma. There was no loss of AQP4 or MOG expression in this patient, while GFAP was abundantly expressed. CONCLUSIONS: These findings suggest that inflammatory cells, including T cells, B cells, plasma cells, and macrophages, are involved in autoimmune GFAP astrocytopathy. Demyelination and astrocyte loss may not necessarily occur in this disease. PMID- 29788019 TI - Robotic Thyroid Surgery: Current Perspectives and Future Considerations. AB - Robotic transaxillary thyroidectomy, pioneered in South Korea, is firmly established throughout the Far East but remains controversial in Western practice. This relates to important population differences (anthropometry and culture) compounded by the smaller mean size of thyroid nodules operated on in South Korea due to a national thyroid cancer screening programme. There is now level 2 evidence (including from Western World centres) to support the safety, feasibility, and equivalence of the robotic approach to its open counterpart in terms of recurrent laryngeal nerve injury, hypoparathyroidism, haemorrhage, and oncological outcomes for differentiated thyroid cancer. Moreover, robotic thyroidectomy has been shown to be superior to open surgery for certain patient reported outcome measures, namely scar cosmesis and pain. Downsides include its high cost, longer operative time, and risk of complications not encountered in open thyroidectomy (brachial plexus neurapraxia). Careful patient selection is paramount as this procedure is not for every patient, surgeon, or hospital. It should only be undertaken by high-volume surgeons operating as part of a multidisciplinary robotic team in specialised centres. Novel robotic approaches utilising the retroauricular and transoral routes for thyroidectomy have recently been described but further studies are required to establish their respective role in modern thyroid surgery. PMID- 29788020 TI - Genomic Deletion Involving the IMMP2L Gene in Two Cases of Autism Spectrum Disorder. AB - Mutations/deletions of the IMMP2L gene have been associated with different cognitive/behavioral disturbances, including autism spectrum disorders (ASD). The penetrance of these defects is not complete since they often are inherited from a healthy parent. Using array-CGH in a cohort of 37 ASD patients, we found 2 subjects harboring a deletion inside the IMMP2L gene. In both cases, the IMMP2L gene deletion was inherited: from a healthy mother in one case and from a dyslectic father in the other. In the latter family, the IMMP2L deletion was also detected in the patient's brother, who showed delayed language development. In a cohort of 100 normal controls, no deletions including the IMMP2L gene were observed. However, a recent meta-analysis found no association between IMMP2L deletions and ASD. Our data would indicate that deletions involving the IMMP2L gene may contribute to the development of a subgroup of cognitive/behavioral disorders. PMID- 29788022 TI - Hospitalizations in Children with a Penicillin Allergy Label: An Assessment of Healthcare Impact. AB - BACKGROUND: Beta-lactam allergy is overdiagnosed. Diagnosis of penicillin allergy has been associated with a greater use of hospital resources and an increased risk of antibiotic-resistant infections, although this issue remains poorly studied in children. We aimed to compare patient characteristics and use of hospital resources in hospitalized children with and without a record of penicillin allergy. METHODS: We identified all hospitalizations in children labelled as being allergic to penicillin in a database containing all hospitalizations in Portuguese public hospitals between 2000 and 2014, and compared these with a similar number of age-, sex-, and main diagnosis-matched hospitalizations without a penicillin allergy label. Comparisons were made for length of hospital stay, comorbidities (Charlson Comorbidity Index), in-hospital mortality, and hospitalization costs. RESULTS: We identified 1,718 hospitalizations corresponding to children labelled as penicillin-allergic. Compared with patients without such a label, these children had longer hospital stays (mean 5 vs. 4 days, p = 0.03) and a higher comorbidity index (mean 0.11 vs. 0.09, p < 0.001). Hospitalization costs were also higher (EUR 2,071 vs. 1,798), but the difference was not significant (p = 0.12). CONCLUSIONS: Hospitalizations of children labelled as allergic to penicillin are associated with longer hospital stays, more comorbidities, and a tendency towards higher hospitalization costs. An accurate diagnosis of penicillin allergy based on clinical history and confirmatory tests is therefore essential in all paediatric patients. PMID- 29788021 TI - Predictors of Cardioembolic Stroke in Japanese Patients with Atrial Fibrillation in the Fushimi AF Registry. AB - BACKGROUND: Large-scale clinical trials have analyzed risk factors for any ischemic stroke in patients with atrial fibrillation (AF). However, the risk factors for cardioembolic stroke (CES), specifically, have not been reported. To clarify the risk factors for CES and clinically significant cardioembolic infarction, we examined the incidence of CES and larger infarct volume (IV) (> 30 mL) CES, employing the Fushimi AF Registry, a community-based prospective cohort of AF patients in the Fushimi ward, Kyoto, Japan. METHODS: A total of 4,182 Fushimi AF patients were enrolled from March 2011 to December 2014. The risk factors for CES were evaluated using multivariate analysis. RESULTS: Of 4,182 patients enrolled, 3,749 patients were observed for >=1 year. During the follow up period (mean duration, 979 +/- 7.7 days), 91/3,749 patients experienced a CES (2.43%). Significant risk factors associated with CES were older age (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.72; p = 0.046), low body weight (OR, 1.30; 95% CI, 1.03-1.65; p = 0.033), sustained AF (OR, 1.67; 95% CI, 1.05 2.71; p = 0.034), and previous stroke or transient ischemic attack (TIA) (OR, 1.94; 95% CI, 1.22-3.06; p = 0.004). Predictors of a large IV were chronic kidney disease (CKD) (OR, 2.08; 95% CI, 1.09-4.05; p = 0.027) and previous stroke/TIA (OR, 2.27; 95% CI, 1.19-4.24; p = 0.011). CONCLUSIONS: In this population-based cohort of Japanese patients with AF, in addition to previous stroke/TIA and older age, sustained AF and low body weight emerged as risk factors for CES, as opposed to any stroke, which may have a different risk profile. Patients with CKD or previous stroke/TIA who developed cardioembolic infarction exhibited more advanced severity. There is a need for direct oral anticoagulants that can be used safely in patients with comorbid AF and CKD. PMID- 29788023 TI - Weight Status of 7-Year-Old Hungarian Children between 2010 and 2016 Using Different Classifications (COSI Hungary). AB - AIMS: To describe the prevalence of thinness, overweight, and obesity in Hungarian children (age 7.0-7.9 years) according to different classifications, to assess the progress between 2010 and 2016, and to investigate whether tendencies differ according to gender. METHODS: A national representative sample was generated by two-stage cluster sampling, and a total of 2,651 children (50.9% boys; age 7.49 +/- 0.3 years) were measured (weight and height) in October 2016. Population estimates were calculated using the WHO, IOTF, and national cut-offs. RESULTS: Prevalence of thinness (including grade 1 and 2) was 12.6% based on the IOTF criteria and 15.6% based on the WHO definition. 22.5% of children were identified as overweight or obese according to the IOTF classification, compared with 28.4% according to the WHO definition. Between 2010 and 2016, each classification indicated possible stability in overweight and obesity prevalence. In contrast, the prevalence of thinness grade 2 almost doubled in 6 years according to all definitions (p < 0.05). No significant gender difference was observed in the progress. CONCLUSION: Overweight and obesity appeared to be stable over 6 years, but we detected growing thinness rates. Routine collection of high-quality data that are based on standardized and comparable methods is essential to monitor the childhood obesity problem. PMID- 29788024 TI - Extracorporeal Photopheresis: An Efficacious and Well-Tolerated Treatment for Cutaneous and Oral Mucosal Chronic Graft-versus-Host Disease. AB - BACKGROUND: Extracorporeal photopheresis (ECP) is a second-line therapy for steroid-refractory chronic graft-versus-host disease (cGVHD). OBJECTIVE: We describe the long-term efficacy and tolerability of ECP according to the cutaneous phenotype of cGVHD and report on the reduced need for immunosuppressant drugs in this setting. PATIENTS AND METHODS: Fourteen patients (8 females) with cutaneous and/or mucosal cGVHD, treated with ECP between October 2010 and May 2016 within a single center, were included. Final analyses included patients who had received ECP for at least 12 months. We prospectively evaluated the efficacy of ECP using lesion-specific clinical scores and by recording changed doses of systemic immunosuppressants. RESULTS: Of the 14 patients, sclerotic skin lesions were present in 10 (71%). The mRODNAN score decreased in all patients from month 9 onwards, with 40 and 77% reductions at 12 and 36 months, respectively. Six patients (43%) presented with cutaneous lichenoid lesions: this score was reduced in all patients by month 3, reaching a 93% reduction by month 12. Five patients (36%) experienced oral mucosal lichenoid lesions: these scores were decreased by 55% at month 12 and by 100% by month 33. The use of systemic immunosuppressants was reduced in all patients; 4 patients could stop all immunosuppressant drugs after 2 years. ECP was stopped in 3 patients after a complete response. No major ECP-associated adverse effects were observed. DISCUSSION AND CONCLUSION: ECP was an effective long-term therapy for oral and cutaneous cGVHD: consequently, dose levels of therapeutic immunosuppression could be reduced. PMID- 29788025 TI - Does 100% Rapid Review Improve Cervical Cancer Screening? AB - OBJECTIVE: The aim of this work was to evaluate 100% rapid review (100% RR) as a useful tool to detect false negative (FN) results. STUDY DESIGN: A sample of 8,677 swabs was investigated; the unsatisfactory and negative results were referred to 100% RR, concordant results were taken as the final diagnosis, while the discordant results were debated in a consensus meeting to reach a conclusion. The positive results were examined by 2 cytologists. The data were entered into SAS statistical software, and the agreement of the 100% RR results with the final diagnosis was tested with the weighted kappa statistic. RESULTS: There was a significant increase in unsatisfactory results from 348 to 1,927, and of positive results from 174 to 349. On the other hand, there was a substantial decrease in negative results from 8,155 to 6,401. Assessing the relative risk of FN results in smears that were not referred to quality control (100% RR) revealed the following results: atypical squamous cells of undetermined significance (ASC-US), 2.93; low-grade squamous intraepithelial lesion (LSIL), 2.72; high-grade squamous intraepithelial lesion/atypical squamous cells - cannot exclude HSIL (HSIL/ASC H), 2.25. Evaluating by age group, a higher risk for LSIL (4.90) and ASC-US (3.85) was observed in patients aged under 25 years, whereas patients between 25 and 64 years and those over 64 years presented a higher risk for HSIL and ASC-H: 2.46 and 2.75, respectively. CONCLUSION: 100% RR is an effective screening tool for FN results in countries where molecular tests for DNA-HPV and prophylactic vaccines are not available in cervical cancer screening programs. PMID- 29788026 TI - Ragweed Pollen Allergy: Burden, Characteristics, and Management of an Imported Allergen Source in Europe. AB - Ambrosia artemisiifolia, also known as common or short ragweed, is an invasive annual flowering herbaceous plant that has its origin in North America. Nowadays, ragweed can be found in many areas worldwide. Ragweed pollen is known for its high potential to cause type I allergic reactions in late summer and autumn and represents a major health problem in America and several countries in Europe. Climate change and urbanization, as well as long distance transport capacity, enhance the spread of ragweed pollen. Therefore ragweed is becoming domestic in non-invaded areas which in turn will increase the sensitization rate. So far 11 ragweed allergens have been described and, according to IgE reactivity, Amb a 1 and Amb a 11 seem to be major allergens. Sensitization rates of the other allergens vary between 10 and 50%. Most of the allergens have already been recombinantly produced, but most of them have not been characterized regarding their allergenic activity, therefore no conclusion on the clinical relevance of all the allergens can be made, which is important and necessary for an accurate diagnosis. Pharmacotherapy is the most common treatment for ragweed pollen allergy but fails to impact on the course of allergy. Allergen-specific immunotherapy (AIT) is the only causative and disease-modifying treatment of allergy with long-lasting effects, but currently it is based on the administration of ragweed pollen extract or Amb a 1 only. In order to improve ragweed pollen AIT, new strategies are required with higher efficacy and safety. PMID- 29788027 TI - The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes. AB - BACKGROUND: Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. OBJECTIVE: To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. METHODS: This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. RESULTS: Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers' vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. CONCLUSIONS: Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted. PMID- 29788028 TI - Atypical Teratoid/Rhabdoid Tumor of the Spinal Cord in a Child: Case Report and Comprehensive Review of the Literature. AB - INTRODUCTION: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is characterized by SMARCB1/INI deletion or mutation in the long arm of chromosome 22 11(22q11.2), also resulting in loss of nuclear expression of INI1 protein immunohistochemically. AT/RT tumors usually occur in children below 3 years. The tumor is usually seen in the cerebellum or the cerebrum, with an extremely rare incidence in the spinal cord. MATERIALS AND METHODS: We report a rare case of AT/RT in a 6-year-old boy who had a primary spinal cord lesion in the thoracolumbar junction. Pathology revealed loss of nuclear staining of INI1 immunohistochemically. This is the first case reported with mixed intraspinal lesion (intra- and extramedullary). The patient underwent two surgeries and received radiotherapy and chemotherapy; however, he died 16 months after the initial presentation. RESULTS AND DISCUSSION: We reviewed the literature on all children with spinal cord AT/RT. The review showed that the cervical region is the most common location of origin, especially in younger children. Reported cases were treated with a combination of surgery, systemic and intrathecal chemotherapy, and radiation therapy, and a survival time of 18 months represented the best outcome. Overall mean survival time was 10 months. PMID- 29788030 TI - Cortical or Trabecular Bone: What's the Difference? PMID- 29788029 TI - International Task Force on Benzodiazepines. PMID- 29788031 TI - Autologous Neurosensory Retinal Transplantation for Unclosed and Large Macular Holes. AB - PURPOSE: The aim of this study was to demonstrate the surgical technique and clinical outcome of autologous neurosensory retinal patch transplantation for recurrent large macular hole (MH)-induced retinal detachment after failed surgery with internal limiting membrane (ILM) removal or transplantation. METHODS: We reviewed 5 patients with recurrent MH-induced retinal detachment after failed surgeries with ILM removal or transplantation who underwent vitrectomy combined with autologous neurosensory retinal patch transplantations and were followed up over 6 months. In the autologous neurosensory retinal patch transplantation procedure, a small piece of neurosensory retina was removed and transplanted inside the MH. The anatomic outcomes of MH-induced retinal detachment were evaluated by fundus examinations and optical coherence tomography. The pre operative and postoperative best-corrected visual acuities (BCVAs) were compared and the MH closure rates were measured as the main outcomes. RESULTS: A total of 5 patients (3 men and 2 women; average age 35.4 +/- 18.72 years) were included in our study. Complete MH sealing was achieved in 5 eyes after autologous neurosensory retinal patch transplantations, and no complications were observed. The mean BCVA was 2.38 +/- 0.57 (range 1.6-3) before surgery, and 1.46 +/- 0.51 (range 1-2) at 6 postoperative months. There was a significant difference in BCVA before versus after the surgery (p < 0.05, paired t test). CONCLUSIONS: Autologous neurosensory retinal patch transplantation is an effective addition to the surgical options for large MH-induced retinal detachment after failed surgery with ILM removal or transplantation. PMID- 29788032 TI - Tracking changes in frailty throughout later life: results from a 17-year longitudinal study in the Netherlands. AB - Background: to better understand the development of frailty with ageing requires longitudinal studies over an extended time period. Objective: to investigate changes in the degree of frailty during later life, and the extent to which changes are determined by socio-demographic characteristics. Methods: six measurement waves of 1,659 Dutch older adults aged 65 years and over in the Longitudinal Aging Study Amsterdam (LASA) yielded 5,211 observations over 17 years. At each wave, the degree of frailty was measured with a 32-item frailty index (FI), employing the deficit accumulation approach. Socio-demographic characteristics included age, sex, educational level and partner status. Generalized Estimating Equation (GEE) analyses were performed to study longitudinal frailty trajectories. Results: higher baseline FI scores were observed in older people, women, and those with lower education or without partner. The overall mean FI score at baseline was 0.17, and increased to 0.39 after 17 years. The average doubling time in the number of deficits was 12.6 years, and this was similar in those aged 65-74 years and those aged 75+. Partner status was associated with changes over time in FI score, whereas sex and educational level were not. Conclusions: this longitudinal study showed that the degree of frailty increased with ageing, faster than the age-related increase previously observed in cross-sectional studies. Even so, the rate of deficit accumulation was relatively stable during later life. PMID- 29788034 TI - Sleep Disorders, Including Sleep Apnea and Hypertension. AB - There is mounting evidence for an association between sleep disorders and hypertension. In obstructive sleep apnea (OSA), there are plausible biological reasons for the development of hypertension, and treatment of OSA results in modest (2-3 mm Hg), adherence-dependent decreases in blood pressure, with larger effects evident in those with resistant hypertension. However, prospective, population-based cohort studies have not yet convincingly demonstrated a link between OSA and incident hypertension, and adequately powered controlled trials of CPAP for the prevention or treatment or hypertension are lacking. While associations have been identified between short sleep duration, insomnia, restless legs syndrome (RLS), shift work, and hypertension, the causative role of these conditions/circumstances is not proven, and further well-designed pathophysiological and/or interventional studies are needed. Particular emphasis should be placed on defining subgroups of hypertensive OSA patients that stand to benefit most from OSA treatment and in understanding the link between sleep apnea and hypertensive disorders of pregnancy. Well-controlled intervention studies are needed in populations with short sleep duration, insomnia, shift work sleep disorder, and RLS to confirm their putative links with hypertension. PMID- 29788035 TI - A Bayesian hidden Potts mixture model for analyzing lung cancer pathology images. AB - Digital pathology imaging of tumor tissues, which captures histological details in high resolution, is fast becoming a routine clinical procedure. Recent developments in deep-learning methods have enabled the identification, characterization, and classification of individual cells from pathology images analysis at a large scale. This creates new opportunities to study the spatial patterns of and interactions among different types of cells. Reliable statistical approaches to modeling such spatial patterns and interactions can provide insight into tumor progression and shed light on the biological mechanisms of cancer. In this article, we consider the problem of modeling a pathology image with irregular locations of three different types of cells: lymphocyte, stromal, and tumor cells. We propose a novel Bayesian hierarchical model, which incorporates a hidden Potts model to project the irregularly distributed cells to a square lattice and a Markov random field prior model to identify regions in a heterogeneous pathology image. The model allows us to quantify the interactions between different types of cells, some of which are clinically meaningful. We use Markov chain Monte Carlo sampling techniques, combined with a double Metropolis Hastings algorithm, in order to simulate samples approximately from a distribution with an intractable normalizing constant. The proposed model was applied to the pathology images of $205$ lung cancer patients from the National Lung Screening trial, and the results show that the interaction strength between tumor and stromal cells predicts patient prognosis (P = $0.005$). This statistical methodology provides a new perspective for understanding the role of cell-cell interactions in cancer progression. PMID- 29788036 TI - Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) Study of Respiratory Syncytial Virus-Associated Deaths in Pediatric Patients in Canada: 2003 to 2013. AB - Background: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are < 0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centres. Methods: Retrospective case series of children 18 years of age or younger with RSV-associated deaths at centres affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) over the period 2003- 2013, inclusive. Cases were identified using RSV-specific ICD codes to capture all deaths where a diagnosis of RSV infection was present. Results: Eleven centres reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range < 1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Health-care associated RSV infections (HAI) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. Conclusion: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs. The precise impact of these strategies on RSV mortality, however, requires further study. PMID- 29788033 TI - Embolism and mechanical resistances play a key role in dehydration tolerance of a perennial grass Dactylis glomerata L. AB - Background and Aims: More intense droughts under climate change threaten species resilience. Hydraulic strategies determine drought survival in woody plants but have been hardly studied in herbaceous species. We explored the intraspecific variability of hydraulic and morphological traits as indicators of dehydration tolerance in a perennial grass, cocksfoot (Dactylis glomerata), which has a large biogeographical distribution in Europe. Methods: Twelve populations of cocksfoot originating from Mediterranean, Temperate and Northern European areas were grown in a controlled environment in pots. Dehydration tolerance, leaf and stem anatomical traits and xylem pressure associated with 88 or 50 % loss of xylem conductance (P88, P50) were measured. Key Results: Across the 12 populations of cocksfoot, P50 ranged from -3.06 to - 6.36 MPa, while P88 ranged from -5.06 to 11.6 MPa. This large intraspecific variability of embolism thresholds corresponded with the biogeographical distribution and some key traits of the populations. In particular, P88 was correlated with dehydration tolerance (r = 0.79). The dehydration-sensitive Temperate populations exhibited the highest P88 (-6.1 MPa). The most dehydration-tolerant Mediterranean populations had the greatest leaf dry matter content and leaf fracture toughness, and the lowest P88 (-10.4 MPa). The Northern populations displayed intermediate trait values, potentially attributable to frost resistance. The thickness of metaxylem vessel walls in stems was highly correlated with P50 (r = -0.92), but no trade-off with stem lignification was observed. The relevance of the linkage between hydraulic and stomatal traits is discussed for drought survival in perennial grasses. Conclusions: Compared with woody species, the large intraspecific variability in dehydration tolerance and embolism resistance within cocksfoot has consequences for its sensitivity to climate change. To better understand adaptive strategies of herbaceous species to increasing drought and frost requires further exploration of the role of hydraulic and mechanical traits using a larger inter- and intraspecific range of species. PMID- 29788037 TI - Mycoplasma Pneumoniae among Children Hospitalized with Community-acquired Pneumonia. AB - Background: The burden and epidemiology of Mycoplasma pneumoniae (Mp) among U.S. children (<18 years) hospitalized with community-acquired pneumonia (CAP) are poorly understood. Methods: In the Etiology of Pneumonia in the Community (EPIC) study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp-PCR-positive and negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: In the EPIC study, 182(8%) children were Mp-PCR-positive (median age: 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 6/169(4%) isolates. Of 178(98%) Mp-PCR-positive children tested for co-pathogens, 50(28%) had >=1 co-pathogen detected. Variables significantly associated with higher odds of Mp detection included age {10-17 years [adjusted odds ratio (aOR): 7.9 (95% confidence interval (CI): 4.5-13.6)] and 5-9 years [aOR: 4.8 (CI: 2.9-7.8)] vs. 2-4 years}, outpatient antibiotics <=5 days pre-admission [aOR: 2.3 (CI: 1.5-3.4)], and co-pathogen detection [aOR: 2.1 (CI: 1.3-3.1)]. Clinical characteristics often seen included hilar lymphadenopathy, rales, headache, sore throat, and decreased breath sounds. Conclusions: Usually considered as a mild respiratory infection, M. pneumoniae was the most commonly detected bacteria among children >=5 years hospitalized with CAP; one-quarter of whom had co-detections. Although associated with clinically non-specific symptoms, there was a need for intensive care support in some cases. M. pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP. PMID- 29788039 TI - Frailty, Neurocognitive Impairment, or Both in Predicting Poor Health Outcomes Among Adults Living with HIV. AB - Background: Neurocognitive impairment (NCI) is strongly associated with frailty in people living with HIV (PLWH); the overlap of frailty and NCI, and the impact on health outcomes in PLWH is unknown. Methods: PLWH in a longitudinal, observational study of aging completed entry evaluations for frailty and NCI. Outcomes were falls (recurrent), increased limitations in independent activities of daily living, or mortality and were combined. Poisson regression models estimated prevalence ratios (PR) for >=1 outcome over 2 years. Results: Among 987 participants, median age at entry was 51 years, 19% were female, median CD4 count was 616 cells/uL, and HIV-1 RNA was <200 copies/mL in 94%. Most (79%) participants had neither frailty nor NCI; 2% had both; 4% had frailty only and 15% had NCI only. Over 2 years of observation, 100 (10%) participants experienced recurrent falls, 175 (18%) worsening IADL limitation, 17 (2%) died, and 254 (26%) experienced at least one of these poor health outcomes. In adjusted models, frailty with NCI was associated with more than double the risk of poor health outcome (PR 2.65; 95% CI 1.98, 3.54); a significant association was also seen with frailty alone (PR 2.26; 95%CI 1.71, 2.99) and NCI alone (PR 1.73; 95% CI 1.36, 2.20). Conclusions: The presence of frailty with NCI was associated with a greater risk of falls, disability or death in PLWH than NCI alone. Interventions that target prevention or reversal of both frailty and NCI (such as increased physical activity) may significantly limit poor health outcomes among PLWH. PMID- 29788040 TI - Performance Comparison of Field Portable Instruments to the Scanning Mobility Particle Sizer Using Monodispersed and Polydispersed Sodium Chloride Aerosols. AB - This study compared the performance of the following field portable aerosol instrument sets to performance of the reference Scanning Mobility Particle Sizer (SMPS): the handheld CPC-3007, the portable aerosol mobility spectrometer (PAMS), the NanoScan scanning mobility particle sizer (NanoScan SMPS) combined with an optical particle sizer (OPS). Tests were conducted with monodispersed and polydispersed aerosols. Monodispersed aerosols were controlled at the approximate concentration of 1 * 105 particles cm-3 and four monodispersed particle sizes of 30, 60, 100, and 300 nm were selected and classified for the monodispersed aerosol test, while three different steady-state concentration levels (low, medium, and high: ~8 * 103, 5 * 104, and 1 * 105 particles cm-3, respectively) were selected for the polydispersed aerosol test. For all four monodispersed aerosol sizes, particle concentrations measured with the NanoScan SMPS were within 13% of those measured with the reference SMPS. Particle concentrations measured with the PAMS were within 25% of those measured with the reference SMPS. Concentrations measured with the handheld condensation particle counter were within 30% of those measured with the reference SMPS. For the polydispersed aerosols, the particle sizes and concentrations measured with the NanoScan-OPS compared most favorably with those measured with the reference SMPS for three different concentration levels of low, medium, and high (concentration deviations <=10% for all three concentration levels; deviations of particle size <=4%). Although the particle-size comparability between the PAMS and the reference SMPS was quite reasonable with the deviations within 10%, the polydispersed particle concentrations measured with the PAMS were within 36% of those measured with the reference SMPS. The results of this evaluation will be useful for selecting a suitable portable device for our next workplace study phase of respiratory protection assessment. This study also provided the advantages and limitations of each individual portable instrument and therefore results from this study can be used by industrial hygienists and safety professionals, with appropriate caution, when selecting a suitable portable instrument for aerosol particle measurement in nanotechnology workplaces. PMID- 29788038 TI - Testing a longitudinal compensation model in premanifest Huntington's disease. AB - The initial stages of neurodegeneration are commonly marked by normal levels of cognitive and motor performance despite the presence of structural brain pathology. Compensation is widely assumed to account for this preserved behaviour, but despite the apparent simplicity of such a concept, it has proven incredibly difficult to demonstrate such a phenomenon and distinguish it from disease-related pathology. Recently, we developed a model of compensation whereby brain activation, behaviour and pathology, components key to understanding compensation, have specific longitudinal trajectories over three phases of progression. Here, we empirically validate our explicit mathematical model by testing for the presence of compensation over time in neurodegeneration. Huntington's disease is an ideal model for examining longitudinal compensation in neurodegeneration as it is both monogenic and fully penetrant, so disease progression and potential compensation can be monitored many years prior to diagnosis. We defined our conditions for compensation as non-linear longitudinal trajectories of brain activity and performance in the presence of linear neuronal degeneration and applied our model of compensation to a large longitudinal cohort of premanifest and early-stage Huntington's disease patients from the multisite Track-On HD study. Focusing on cognitive and motor networks, we integrated progressive volume loss, task and resting state functional MRI and cognitive and motor behaviour across three sequential phases of neurodegenerative disease progression, adjusted for genetic disease load. Multivariate linear mixed models were fitted and trajectories for each variable tested. Our conceptualization of compensation was partially realized across certain motor and cognitive networks at differing levels. We found several significant network trends that were more complex than that hypothesized in our model. These trends suggest changes to our theoretical model where the network effects are delayed relative to performance effects. There was evidence of compensation primarily in the prefrontal component of the cognitive network, with increased effective connectivity between the left and right dorsolateral prefrontal cortex. Having developed an operational model for the explicit testing of longitudinal compensation in neurodegeneration, it appears that general patterns of our framework are consistent with the empirical data. With the proposed modifications, our operational model of compensation can be used to test for both cross-sectional and longitudinal compensation in neurodegenerative disease with similar patterns to Huntington's disease. PMID- 29788042 TI - Structure-Function Relationships in Endocrinology. PMID- 29788041 TI - Do older and younger patients derive similar survival benefits from novel oncology drugs? A systematic review and meta-analysis. AB - Background: older patients are commonly believed to derive less benefit from cancer drugs, even if they fulfil clinical trial eligibility [Talarico et al. (2004, J Clin Oncol, 22(22):4626-31)]. We aim to examine if novel oncology drugs provide differential age-based treatment outcomes for patients on clinical trials. Methods: a systematic review of randomised control trials (RCTs) cited for clinical efficacy evidence in novel oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between 2006 and 2017 was conducted. Studies reporting age-based subgroup analyses for overall or progression-free survival (OS/PFS) were included. Hazard ratios (HRs) and confidence intervals (CIs) for age-based subgroups were extracted. Meta-analyses with random effects were conducted, examining patient subgroups <65 and >=65 years separately and pooled HRs of studies primary endpoints (OS or PFS) compared to examine if differences existed between age-based subgroups. Sensitivity analyses were conducted for cancer type, primary endpoint and systemic treatment. Results: one-hundred-two RCTs, including 65,122 patients, met the inclusion criteria. One study reported age-based toxicity and none reported age-based quality of life (QOL) results. Pooled HRs [95% CIs] for patients <65 and >=65 years were 0.61 [0.57-0.65] and 0.65 [0.61-0.70], respectively, with no difference between them (P = 0.14). Sensitivity analyses revealed similar results. Conclusion: our results suggest that older and young patients, who fulfil clinical trial eligibility, may derive similar relative survival benefits from novel oncology drugs. There is, however, a need to report age-based toxicity and QOL results to support patient discussions regarding the balance of treatment benefit and harm, to encourage informed decision-making. PMID- 29788043 TI - Reply to Garcia-Granja et al. PMID- 29788044 TI - Clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation: a 7-year experience. AB - Aims: We analysed the early and long-term clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation (TMVI) in an experienced centre. Methods and results: All patients undergoing TMVI from July 2010 to July 2017 in our centre were prospectively included. Indication for TMVI relied on the judgement of the local heart team. Patients were followed at 1 month, 1 year, and yearly thereafter. A total of 91 patients underwent TMVI. The median age was 73 (57-81) years and 70% of patients were women. Patients were at high risk for surgery with a median EuroSCORE II of 9.6 (4.0-14.6) %. Indication for TMVI was bioprosthesis failure (valve-in-valve) in 37.3%, annuloplasty failure (valve-in-ring) in 33.0%, and severe mitral annulus calcification (MAC) in 29.7%. The transseptal approach was used in 92.3% of patients and balloon expandable valves were used in all patients. Technical success was achieved in 84.6% of patients, one patient died during the procedure and haemodynamically significant left ventricular outflow tract obstruction occurred in three patients (3.3%). At 30 days, 7.7% of patients had died, without significant differences between groups, and a major stroke occurred in 2.2% of patients. The cumulative rates of all-cause mortality at 1-year and 2-year follow-up were 21.0% [95% confidence interval (CI) 9.9-38.8] and 35.7% (95% CI 19.2-56.5), respectively, with a higher late mortality in patients with MAC. The 2-year rates of re intervention and valve thrombosis were 8.8% and 14.4%, respectively. At 6 months to 1 year, 68.9% of patients were in New York Heart Association Class I or II, and 90.7% of patients had mild or less mitral regurgitation. The mean transmitral gradient decreased from 9.3 +/- 3.9 mmHg at baseline to 6.0 +/- 2.3 mmHg at discharge (P < 0.001) without changes at 6-month to 1-year follow-up. Conclusion: Transcatheter mitral valve implantation using balloon-expandable valves in selected patients with bioprosthesis or annuloplasty failure or severe MAC was associated with a low rate of peri-procedural complications and acceptable long term outcomes. PMID- 29788046 TI - A carnivore embryo's perspective on essential amino acids and ammonium in culture medium: effects on the development of feline embryos. AB - Carnivores are an interesting model for studies of embryonic amino acid metabolism and ammonium (NH4+) toxicity given the high protein content of their diets. Our objectives were to examine concentration- and stage-specific effects of essential amino acids (EAA; 0x, 0.125x, 0.25x, 0.5x, or 1.0x the concentrations in Minimum Essential Medium) and NH4+ (0, 300, or 600 MUM) on the development and metabolism of feline embryos. The presence of EAA, regardless of concentration, during days 3 to 7 of culture increased (P < 0.01) the proportion of embryos that initiated hatching (>14.3%) and the total number of cells per blastocyst (>148.3 cells) compared to embryos cultured without EAA (0.0% and 113.2 +/- 3.7 cells, respectively). The presence of EAA during days 1 to 3 (0.25x) and 3 to 7 (1.0x) of culture increased (P < 0.01) the proportions of embryos that formed blastocysts (82.9 +/- 4.2%) and initiated hatching (32.9 +/- 5.2%), and the number of cells per blastocyst (247.9 +/- 12.1 cells), compared to control embryos (60.0 +/- 5.3%, 0.0%, 123.2 +/- 8.1 cells, respectively). The presence of NH4+ in the medium did not affect (P > 0.05) development of feline embryos. The addition of EAA or NH4+ during culture did not affect (P > 0.05) the production of Gln by feline embryos, but decreased (P < 0.05) production of Ala and increased (P < 0.05) production of urea. Additional work is needed to determine if our observations are unique to feline embryos or reflect an adaptation to a high protein diet that is conserved in other carnivores. PMID- 29788045 TI - Molecular epidemiology of Candida auris in Colombia reveals a highly-related, country-wide colonization with regional patterns in Amphotericin B resistance. AB - Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in four hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into four zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven (41%) of the 17 people swabbed were found to be colonized. C. auris was isolated from 37/322 (12%) environmental samples. These were collected from a variety of items in all four zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel non-synonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility. PMID- 29788047 TI - Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction. AB - Aims: Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF. Methods and results: Subjects with invasively-proven HFpEF (n = 50) and non cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve. Conclusion: This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF. PMID- 29788049 TI - Evidence that divergent selection shapes a developmental cline in a forest tree species complex. AB - Background and Aims: Evolutionary change in developmental trajectories (heterochrony) is a major mechanism of adaptation in plants and animals. However, there are few detailed studies of the variation in the timing of developmental events among wild populations. We here aimed to identify the climatic drivers and measure selection shaping a genetic-based developmental cline among populations of an endemic tree species complex on the island of Tasmania. Methods: Seed lots from 38 native provenances encompassing the clinal transition from the heteroblastic Eucalyptus tenuiramis to the homoblastic Eucalyptus risdonii were grown in a common-garden field trial in southern Tasmania for 20 years. We used 27 climatic variables to model the provenance variation in vegetative juvenility as assessed at age 5 years. A phenotypic selection analysis was used to measure the fitness consequences of variation in vegetative juvenility based on its impact on the survival and reproductive capacity of survivors at age 20 years. Key Results: Significant provenance divergence in vegetative juvenility was shown to be associated with home-site aridity, with the retention of juvenile foliage increasing with increasing aridity. Our results indicated that climate change may lead to different directions of selection across the geographic range of the complex, and in our mesic field site demonstrated that total directional selection within phenotypically variable provenances was in favour of reduced vegetative juvenility. Conclusions: We provide evidence that heteroblasty is adaptive and argue that, in assessing the impacts of rapid global change, developmental plasticity and heterochrony are underappreciated processes which can contribute to populations of long-lived organisms, such as trees, persisting and ultimately adapting to environmental change. PMID- 29788048 TI - Robustness of Transposable Element Regulation but No Genomic Shock Observed in Interspecific Arabidopsis Hybrids. AB - The merging of two divergent genomes in a hybrid is believed to trigger a "genomic shock", disrupting gene regulation and transposable element (TE) silencing. Here, we tested this expectation by comparing the pattern of expression of transposable elements in their native and hybrid genomic context. For this, we sequenced the transcriptome of the Arabidopsis thaliana genotype Col 0, the A. lyrata genotype MN47 and their F1 hybrid. Contrary to expectations, we observe that the level of TE expression in the hybrid is strongly correlated to levels in the parental species. We detect that at most 1.1% of expressed transposable elements belonging to two specific subfamilies change their expression level upon hybridization. Most of these changes, however, are of small magnitude. We observe that the few hybrid-specific modifications in TE expression are more likely to occur when TE insertions are close to genes. In addition, changes in epigenetic histone marks H3K9me2 and H3K27me3 following hybridization do not coincide with TEs with changed expression. Finally, we further examined TE expression in parents and hybrids exposed to severe dehydration stress. Despite the major reorganization of gene and TE expression by stress, we observe that hybridization does not lead to increased disorganization of TE expression in the hybrid. Although our study did not examine TE transposition activity in hybrids, the examination of the transcriptome shows that TE expression is globally robust to hybridization. The term "genomic shock" is perhaps not appropriate to describe transcriptional modification in a viable hybrid merging divergent genomes. PMID- 29788050 TI - Rabies Preexposure Prophylaxis: Application of Updated World Health Organization Position to Travelers. PMID- 29788051 TI - Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension. AB - Aims: Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Methods and results: Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2 fold increase in having a moderate clinical event. Conclusion: MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH. PMID- 29788053 TI - Reversing Ongoing Chronic Intestinal Inflammation and Fibrosis by Sustained Block of IL-12 and IL-23 Using a Vaccine in Mice. AB - Interleukin (IL)-12 and IL-23 that share subunit p40 are important cytokines in the pathogenesis of inflammatory bowel disease. We reported that mouse p40 peptide-based vaccines ameliorated intestinal inflammation in the prevention of trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. Here, we evaluated whether administration of the vaccine after establishment of colitis would be effective in modifying both TNBS-induced and dextran sulfate sodium (DSS)-induced chronic colitis and the underlying immune mechanisms. We further examined whether vaccination could exacerbate infections. Chronic colitis was developed by either intrarectally administrating TNBS or drinking 4% DSS water. Vaccination started after two TNBS administrations or 7 days of DSS treatment. Results showed that administrating p40 vaccine induced high tittered antibodies to IL-12 and IL-23, improved clinical scores, reduced intestinal inflammation and fibrosis, and down-regulated proinflammatory cytokine productions in colon tissue, compared with control mice. Furthermore, in lamina propria mononuclear cells and/or mesenteric lymph nodes, mice immunized with p40 peptide vaccine exhibited high ratios of Treg/Th1 and Treg/Th17 cells and increased IL-10 expression in CD11c+IL-10+cells. In mice infected with lung chlamydia, in which the protective role of Th1/Th17 is well documented, vaccine immunization did not increase lung bacterial burden. We conclude that p40 vaccine may provide a potential and safe approach for treatment of IBD. 10.1093/ibd/izy142_videoizy142.video5785979965001. PMID- 29788054 TI - Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi. AB - Background: Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Methods: Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Results: Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Conclusions: Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs. PMID- 29788055 TI - Clinical Benefit of Capsule Endoscopy in Crohn's Disease: Impact on Patient Management and Prevalence of Proximal Small Bowel Involvement. AB - Background: Ileocolonoscopy and computed tomography (CT) or magnetic resonance (MR) enterography (CTE/MRE) are utilized to evaluate patients with small bowel (SB) Crohn's disease (CD). The purpose of our study was to estimate the impact of capsule endoscopy (CE) on patient management after clinical assessment, ileocolonoscopy, and CTE/MRE. Methods: We prospectively analyzed 50 adult CD patients without strictures at clinically indicated ileocolonoscopy and CTE/MRE exams. Providers completed pre- and post-CE clinical management questionnaires. Pre-CE questionnaire assessed likelihood of active SBCD and management plan using a 5-point level of confidence (LOC) scales. Post-CE questionnaire assessed alteration in management plans and contribution of CE findings to these changes. A change of >=2 on LOC scale was considered clinically meaningful. Results: Of the 50 patients evaluated (60% females), median age was 38 years, median disease duration was 3 years, and median Crohn's Disease Activity Index (CDAI) score was 238 points. All CTE/MRE studies were negative for proximal disease. CE detected proximal disease in 14 patients (28%) with a median Lewis score of 215 points. CE findings altered management in 17 cases (34%). The most frequent provider perceived benefits of CE were addition of new medication (29%) and exclusion of active SB mucosal disease (24%). Conclusion: CE is a safe imaging modality that alters clinical management in patients with established SBCD by adding incremental information not available at ileocolonoscopy and cross-sectional enterography. PMID- 29788056 TI - Bacterial biofilm formation on the hyphae of ectomycorrhizal fungi: a widespread ability under controls? AB - Ectomycorrhizal (ECM) fungi establish symbiosis with roots of most trees of boreal and temperate ecosystems and are major drivers of nutrient fluxes between trees and the soil. ECM fungi constantly interact with bacteria all along their life cycle and the extended networks of hyphae provide a habitat for complex bacterial communities. Despite the important effects these bacteria can have on the growth and activities of ECM fungi, little is known about the mechanisms by which these microorganisms interact. Here we investigated the ability of bacteria to form biofilm on the hyphae of the ECM fungus Laccaria bicolor. We showed that the ability to form biofilms on the hyphae of the ECM fungus is widely shared among soil bacteria. Conversely, some fungi, belonging to the Ascomycete class, did not allow for the formation of bacterial biofilms on their surfaces. The formation of biofilms was also modulated by the presence of tree roots and ectomycorrhizae, suggesting that biofilm formation does not occur randomly in soil but that it is regulated by several biotic factors. In addition, our study demonstrated that the formation of bacterial biofilm on fungal hyphae relies on the production of networks of filaments made of extracellular DNA. PMID- 29788057 TI - Haustorium-endosperm relationships and the integration between developmental pathways during reserve mobilization in Butia capitata (Arecaceae) seeds. AB - Background and Aims: Palm seeds are interesting models for studying seed reserve mobilization at the tissue level due to the abundance and complexity of reserves stored in their living endosperm cells and the development of a highly specialized haustorium. We studied structural and physiological aspects of the initial phases of reserve mobilization in seeds of a neotropical palm, Butia capitata, and sought to characterize the interactions between the different developmental pathways of the haustorium and endosperm. Methods: Morphological and histochemical evaluations of the haustorium, the endosperm adjacent to the embryo, and the peripheral endosperm of dry, imbibed, dormant seeds and seeds geminating for 2, 5 and 10 d were performed. Biochemical analyses included determinations of endo-beta-mannanase activity, hormonal profiling (20 hormones belonging to eight classes) and H2O2 quantification in various tissues. Key Results: The mobilization of haustorium reserves was associated with germination and involved distinct hormonal alterations in the endosperm related to H2O2 production. The mobilization of endosperm reserves occurred as a post-germination event controlled by the seedling and involved major structural changes in the haustorium, including growth (which increased contact with, and pressure on, the endosperm) and the formation of an aerenchyma (thus facilitating O2 diffusion). The flow of O2 to the endosperm and changes in endogenous contents of H2O2 and hormones (cytokinins, auxins, brassinosteroids and ethylene) induced the establishment of an endosperm digestion zone and the translocation of reserves to the haustorium. Conclusions: The haustorium-endosperm relationship during reserve mobilization plays a pivotal role in signal integration between growth and degradation pathways in germinating seeds of Butia capitata. PMID- 29788058 TI - Modeling Immunization To Infliximab in Children With Crohn's Disease Using Population Pharmacokinetics: A Pilot Study. AB - Background: Antidrug antibodies (ADAs) dramatically increase infliximab clearance and are responsible for underexposure to the drug, leading to treatment failure. This pilot study aimed at developing a population pharmacokinetic model to detect and describe an early increase in infliximab clearance due to ADA. Methods: Twenty children with Crohn's disease (CD) were followed for 1 year or until treatment failure. Infliximab trough concentration, ADA, C-reactive protein (CRP), and Paediatric Crohn's Disease Activity Index (PCDAI) were recorded at each visit. A time-varying clearance population pharmacokinetic model was built to detect and describe an increase in infliximab clearance, independent from ADA testing. Factors associated with clearance variation and the relationships between infliximab concentrations, clearance variation, and clinical response were investigated. Results: The model detected important increases in clearance in 4 patients. These patients had suboptimal early response, with higher mean PCDAI (P = 0.0086) and CRP (P = 0.028) compared with other patients. Two of them had detectable ADA. Clearance increase as described by the model and lower infliximab trough concentration at week 2 were associated with poorer outcomes in a multivariate Cox model (P = 0.001 and P = 0.0048, respectively). Conclusions: Being able to detect an increase in infliximab clearance, this model could allow the early detection of immunization to infliximab and therefore could help with dose adjustment in patients with CD. Moreover, the results suggest that clearance variations could be used as a predictive marker of clinical response. These findings need to be confirmed in a larger cohort, however, and predictive factors of clearance increase have to be investigated. PMID- 29788052 TI - Fast Evolution and Lineage-Specific Gene Family Expansions of Aphid Salivary Effectors Driven by Interactions with Host-Plants. AB - Effector proteins play crucial roles in plant-parasite interactions by suppressing plant defenses and hijacking plant physiological responses to facilitate parasite invasion and propagation. Although effector proteins have been characterized in many microbial plant pathogens, their nature and role in adaptation to host plants are largely unknown in insect herbivores. Aphids rely on salivary effector proteins injected into the host plants to promote phloem sap uptake. Therefore, gaining insight into the repertoire and evolution of aphid effectors is key to unveiling the mechanisms responsible for aphid virulence and host plant specialization. With this aim in mind, we assembled catalogues of putative effectors in the legume specialist aphid, Acyrthosiphon pisum, using transcriptomics and proteomics approaches. We identified 3,603 candidate effector genes predicted to be expressed in A. pisum salivary glands (SGs), and 740 of which displayed up-regulated expression in SGs in comparison to the alimentary tract. A search for orthologs in 17 arthropod genomes revealed that SG-up regulated effector candidates of A. pisum are enriched in aphid-specific genes and tend to evolve faster compared with the whole gene set. We also found that a large fraction of proteins detected in the A. pisum saliva belonged to three gene families, of which certain members show evidence consistent with positive selection. Overall, this comprehensive analysis suggests that the large repertoire of effector candidates in A. pisum constitutes a source of novelties promoting plant adaptation to legumes. PMID- 29788059 TI - Impact of right ventricular volume and function evaluated using cardiovascular magnetic resonance imaging on outcomes after surgical ventricular reconstruction. AB - OBJECTIVES: This study aimed to evaluate whether cardiac magnetic resonance imaging (MRI)-derived right ventricular (RV) assessment can facilitate risk stratification among patients with ischaemic cardiomyopathy who underwent surgical ventricular reconstruction (SVR). METHODS: We retrospectively analysed 53 patients who underwent SVR. The patients were preoperatively evaluated using cardiac MRI. Cine-MRI was acquired for left ventricular (LV) and RV volume. Gadolinium-enhanced MRI was performed to evaluate LV scarring. The mid-term (median, 58 months) risk factors of all-cause mortality and major adverse cardiac events were analysed. RESULTS: A significant reduction in LV end-diastolic and end-systolic volume index and an increase in LV ejection fraction were observed early after SVR. RV end-diastolic volume index (RVEDVI) and RV end-systolic volume index (RVESVI) decreased after SVR (preoperative versus postoperative: RVEDVI, 71 +/- 24 vs 62 +/- 17 ml/m2, P = 0.006; RVESVI, 44 +/- 26 vs 37 +/- 16 ml/m2, P = 0.033), but RV ejection fraction did not change (preoperative versus postoperative: RV ejection fraction 40.8+/-14.6 vs 42.0+/-11.0%, P = 0.067). At follow-up, 25 deaths and 31 major adverse cardiac events occurred. After adjustment for age, creatinine level and preoperative mitral regurgitation grade, the Cox-hazard model indicated that RVEDVI [P = 0.006, hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05] and RVESVI [P = 0.007, HR 1.02, 95% CI 1.01-1.04] were significant predictors for all-cause mortality. As for major adverse cardiac events, RVEDVI (P = 0.007, HR 1.03, 95% CI 1.01-1.05), RVESVI (P = 0.002, HR 1.03, 95% CI 1.01-1.04) and RV ejection fraction (P = 0.018, HR 0.97, 95% CI 0.94-0.99) were significant. CONCLUSIONS: RV parameters were more sensitive than LV parameters for predicting worse outcomes following SVR. Preoperative assessment of RV volume and function using cardiac MRI may improve the risk stratification of SVR. PMID- 29788060 TI - Yeast mitochondria: an overview of mitochondrial biology and the potential of mitochondrial systems biology. AB - Mitochondria are dynamic organelles of endosymbiotic origin that are essential components of eukaryal cells. They contain their own genetic machinery, have multicopy genomes and like their bacterial ancestors they consist of two membranes. However, the majority of the ancestral genome has been lost or transferred to the nuclear genome of the host, preserving only a core set of genes involved in oxidative phosphorylation. Mitochondria perform numerous biological tasks ranging from bioenergetics to production of protein co-factors, including heme and iron-sulfur clusters. Due to the importance of mitochondria in many cellular processes, mitochondrial dysfunction is implicated in a wide variety of human disorders. Much of our current knowledge on mitochondrial function and dysfunction comes from studies using Saccharomyces cerevisiae. This yeast has good fermenting capacity, rendering tolerance to mutations that inactivate oxidative phosphorylation and complete loss of mitochondrial DNA. Here, we review yeast mitochondrial metabolism and function with focus on S. cerevisiae and its contribution in understanding mitochondrial biology. We further review how systems biology studies, including mathematical modeling, has allowed gaining new insight into mitochondrial function, and argue that this approach may enable us to gain a holistic view on how mitochondrial function interacts with different cellular processes. PMID- 29788061 TI - Regulation of the heat shock transcription factor Hsf1 in fungi: implications for temperature-dependent virulence traits. AB - The impact of fungal pathogens on human health is devastating. For fungi and other pathogens, a key determinant of virulence is the capacity to thrive at host temperatures, with elevated temperature in the form of fever as a ubiquitous host response to defend against infection. A prominent feature of cells experiencing heat stress is the increased expression of heat shock proteins (Hsps) that play pivotal roles in the refolding of misfolded proteins in order to restore cellular homeostasis. Transcriptional activation of this heat shock response is orchestrated by the essential heat shock transcription factor, Hsf1. Although the influence of Hsf1 on cellular stress responses has been studied for decades, many aspects of its regulation and function remain largely enigmatic. In this review, we highlight our current understanding of how Hsf1 is regulated and activated in the model yeast Saccharomyces cerevisiae, and highlight exciting recent discoveries related to its diverse functions under both basal and stress conditions. Given that thermal adaption is a fundamental requirement for growth and virulence in fungal pathogens, we also compare and contrast Hsf1 activation and function in other fungal species with an emphasis on its role as a critical regulator of virulence traits. PMID- 29788062 TI - Strained Bedfellows: An Actor-Partner Analysis of Spousal Attachment Insecurity and Sleep Quality. AB - Background: The quality of interpersonal ties-especially closer relationships appears to be associated with physical health outcomes. Sleep is one pathway through which relationships and health appear to be linked, but this has been inadequately investigated in the context of dyadic attachment. Purpose: The present study examined links between relationship-specific attachment anxiety (which can involve preoccupation with one's partner, negative relationship cognitions, and fear of abandonment) and avoidance (e.g., low emotional investment or intimacy) and sleep quality. Methods: Attachment, assessed using the Experience in Close Relationship (ECR), was used to predict Pittsburgh Sleep Quality Inventory (PSQI)-assessed sleep quality in 92 married heterosexual couples via actor-partner interdependence models. Depression was examined as a potential mediator of this association. Results: Consistent with hypotheses, actors' anxious attachment predicted diminished quality of their own sleep, whereas actors' avoidant attachment was unrelated to their own sleep quality. Results further suggested that couples in which both spouses were higher in attachment anxiety experience better sleep quality (b = -0.74, SE = 0.28, p = .0082, 95% CI [-1.287, -0.196]). Conversely, couples in which both spouses were higher in attachment avoidance showed poorer sleep quality (b = 0.56, SE = 0.23, p = .0188, 95% CI [0.095, 1.016]). These effects were found to be independent of marital satisfaction and depression. Some evidence was also consistent with mediation of links between attachment and sleep quality via depression. Conclusions: Results suggest adult romantic attachment and sleep are associated in complex ways, highlighting the importance of dyadic approaches to the study of relationships, sleep, and health. PMID- 29788063 TI - Lack of Difference in Treatment Patterns and Clinical Outcomes Between Black and White Patients With Inflammatory Bowel Disease. AB - Background: Previous reports have shown differences in phenotypes among black patients with inflammatory bowel disease (IBD) compared with other racial groups, but prior studies were limited by small numbers of black patients and cross sectional analyses. We used data from the Sinai-Helmsley Alliance for Research Excellence cohort to compare phenotypes and treatment patterns of black and white patients with IBD in a prospective study. Methods: We compared phenotypes, IBD specific therapies, and health care utilization among black and white patients with IBD. For all analyses, we performed bivariate analyses and multivariable logistic regression to adjust for potential confounders. Results: Among 5537 patients with IBD, 314 (6%) reported black race. Black patients were more likely to report a Crohn's disease (CD)-related complication at baseline (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.06-1.95). Black patients with CD were more likely to develop a new abscess (aOR, 2.27; 95% CI, 1.31-3.93) and initiate an anti-tumor necrosis factor therapy during follow-up (aOR, 1.85; 95% CI, 1.09-3.14). Black patients with ulcerative colitis were more likely to have proctitis (24% vs 13%, P = 0.033) at baseline. There were no differences in surgery or hospitalization rates during the follow-up period. Conclusions: Black patients with CD demonstrated increased complications at baseline and during follow-up in this cohort. Despite more complicated disease, black and white patients with IBD were generally given the same medications and experienced similar rates of hospitalization and surgery during the study period. In our multicenter cohort, clinical outcomes among black and white patients with IBD were similar. PMID- 29788065 TI - Commentary on: The Risk of Skin Necrosis Following Hyaluronic Acid Filler Injection in Patients With a History of Cosmetic Rhinoplasty. PMID- 29788064 TI - Project-based learning methodology in the area of microbiology applied to undergraduate medical research. AB - In the recent years, there has been a decrease in the number of medical professionals dedicated to a research career. There is evidence that students with a research experience during their training acquire knowledge and skills that increase the probability of getting involved in research more successfully. In the Degree of Medicine (University of the Basque Country) the annual core subject 'Research Project' introduces students to research. The aim of this work was to implement a project-based learning methodology, with the students working on microbiology, and to analyse its result along time. Given an initial scenario, the students had to come up with a research idea related to medical microbiology and to carry out a research project, including writing a funding proposal, developing the experimental assays and analyzing and presenting their results to a congress organized by the University. Summative assessment was performed by both students and teachers. A satisfaction survey was carried out to gather the students' opinion. The overall results regarding to the classroom dynamics, learning results and motivation after the implementation were favourable. Students referred a greater interest about research than they had before. They would choose the project based methodology versus the traditional one. PMID- 29788067 TI - Control of Multidrug-Resistant Pseudomonas aeruginosa in Allogeneic Hematopoietic Stem Cell Transplant Recipients by a Novel Bundle Including Remodeling of Sanitary and Water Supply Systems. PMID- 29788066 TI - Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study. AB - Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 +/- 38.4 mg/dL; week 48: 171.0 +/- 35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 +/- 1.2; week 48: 4.0 +/- 1.2), HDL (baseline: 49.1 +/- 12.0 mg/dL; week 48: 49.2 +/- 45.8 mg/dL), LDL (baseline: 119.2 +/- 30.2 mg/dL; week 48: 114.2 +/- 110.7 mg/dL), and triglycerides (baseline: 136.6 +/- 86.8 mg/dL; week 48: 113.4 +/- 67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 +/- 48.8 mg/dL; week 48: 173.4 +/- 36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 +/- 1.6; week 48: 4.0 +/- 1.2), HDL (baseline: 46.4 +/- 12.5 mg/dL; week 48: 52.1 +/- 54.4 mg/dL), LDL (baseline: 127.0 +/- 36.3 mg/dL; week 48: 111.4 +/- 35.8 mg/dL), and triglycerides (baseline: 167.6 +/- 107.7 mg/dL; week 48: 122.7 +/- 72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients. PMID- 29788068 TI - Commentary on: Treatment of Nasal Deviation With Underlying Bony Asymmetry Secondary to Augmentation Rhinoplasty in Asian Patients. PMID- 29788069 TI - Inflammatory Bowel Disease and Parkinson's Disease: A Nationwide Swedish Cohort Study. AB - Background: Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD). Methods: To estimate the incidence and relative risk of PD development in a cohort of adult IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis [UC]: n = 24,422; Crohn's disease [CD]: n = 11,418; IBD-unclassified [IBD-U]: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520). In a cohort design, all incident PD occurring after the index date was included from the NPR. In a case-control design, all incident PD occurring before the index date was included. The association between IBD and PD and vice versa was investigated by multivariable Cox and logistic regression. Results: In IBD, there were 103 cases of incident PD, resulting in hazard ratios (HRs) for PD of 1.3 (95% confidence interval [CI], 1.0-1.7; P = 0.04) in UC, 1.1 (95% CI, 0.7 1.7) in CD, and 1.7 (95% CI, 0.8-3.0) in IBD-U. However, these effects disappeared when adjusting for number of medical visits during follow-up to minimize potential surveillance bias. In a case-control analysis, IBD patients were more likely to have prevalent PD at the time of IBD diagnosis than matched controls, with odds ratios of 1.4 (95% CI, 1.2-1.8) in all IBD patients, 1.4 (95% CI, 1.1-1.9) for UC, and 1.6 (95% CI, 1.1-2.3) for CD patients alone. Conclusions: IBD is associated with an increased risk of PD, but some of this association might be explained by surveillance bias. 10.1093/ibd/izy190_video1izy190.video15785623138001. PMID- 29788071 TI - Educating Australian musicians: are we playing it safe? AB - The effectiveness of health promotion through arts engagement, and the health benefits and social importance of music in particular, are becoming increasingly recognized. However, like sport, music-making is an athletic endeavour, one that often involves high physiological and psychological loadings on the bodies and minds of musicians. Research over the past 30 years has revealed alarming rates of injury among musicians, and has identified health risk factors associated with music performance faced by professional and student musicians. Australia lacks consistent provision of essential health education for musicians, and research shows an unacceptably high prevalence of performance-related health problems among musicians of all ages. This article advocates for effective health promotion to be embraced in the policies and practices of Australian music performance organizations and educational bodies. It argues that a cultural shift is required, recognizing that a settings-based approach to health literacy is as fundamentally important for musicians as it is for any other occupation or athletic activity. Embedding health education into the delivery of music education will not only help to prevent injury over the lifespan of Australian musicians, it will support and sustain their capacity to contribute towards societal wellbeing and public health outcomes. PMID- 29788070 TI - VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice. AB - Background: Chronic mucocutaneous candidiasis (CMC) treatment often induces drug resistance, posing long-term challenges. A novel broad-spectrum fungal CYP51 inhibitor, VT-1598, specifically targets fungal CYP51, but not human CYP enzymes. Objectives: To determine the efficacy of VT-1598 in the treatment of oral Candida infection caused by fluconazole-susceptible and -resistant clinical isolates. Methods: The MICs of VT-1598 and fluconazole for 28 Candida isolates recovered from patients with inherited CMC were determined using CLSI M27-A3 and M27-S4 guidelines. Plasma and tongue VT-1598 or fluconazole concentrations were measured in mice following oral administration to determine tissue distribution. Tongue fungal load was determined in IL-17 signalling-deficient Act1-/- mice following sublingual Candida albicans infection and oral treatment with fluconazole or VT 1598. Results: Among the 28 Candida isolates, 10 (36%) had fluconazole MICs of >=4 mg/L, whereas VT-1598 demonstrated potent in vitro activity against all isolates (MIC90, 0.125 mg/L). After oral administration, VT-1598 levels in mouse plasma and tongue were significantly greater than those of fluconazole. In vivo, VT-1598 exhibited significant efficacy against fluconazole-susceptible and resistant C. albicans, even at low drug doses. Furthermore, after a 10 day washout period, tongue fungal burdens in fluconazole-treated mice returned to vehicle control levels, whereas, in contrast, they were undetectable in mice treated with VT-1598. Conclusions: VT-1598 effectively controls in vitro growth of mucosally derived Candida clinical isolates, including fluconazole-resistant strains. In vivo, VT-1598 eliminates C. albicans, even after a long washout period or at low doses. Therefore, VT-1598 is a promising drug candidate that may significantly improve treatment options for CMC patients. PMID- 29788072 TI - Mathematical Models for Predicting Development of Orius majusculus (Heteroptera: Anthocoridae) and Its Applicability to Biological Control. AB - Complete development of Orius majusculus Reuter (Heteroptera: Anthocoridae) at nine constant temperatures, between 12 and 34 degrees C, was evaluated under laboratory conditions. The maximum developmental period of 90.75 d occurred at 12 degrees C, whereas the minimum of 11.34 d occurred at 30 degrees C. From 30 to 34 degrees C, the developmental period increased to 13.50 d. Between 21 and 33 degrees C the survival rate was more than 80%. The optimal temperature when considering developmental rate and survival was between 24 and 30 degrees C. At constant temperatures, four models were developed, one of which was linear and three nonlinear (Logan type III, Lactin, and Briere). All models were validated under field conditions and diel temperature variations. The values of the adjusted determination coefficients of the linear (>0.77) and nonlinear models (>0.93) were high. The thermal requirement for complete development, from egg to adult, was 284.5 degree-days (DD). In all nonlinear models, elevated levels of accuracy (>=90.31%) in field validation were also obtained, especially in the Briere model. With the results obtained herein, the optimization of O. majusculus mass rearing, its ideal use, and field management in biological control strategies can be improved. PMID- 29788073 TI - Video-assisted thoracoscopic anterior vertebral body tethering for the correction of adolescent idiopathic scoliosis of the spine. AB - Adolescent idiopathic scoliosis affects children aged 11-18 years. Severe disease may necessitate spinal fusion. Vertebral body tethering gradually corrects scoliosis as the patients grow. The application of video-assisted thoracic surgery to the thoracic spine is a new area for further development. PMID- 29788074 TI - Efficacy of anthelminthic drugs and drug combinations against soil-transmitted helminths: a systematic review and network meta-analysis. AB - Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STH) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis, comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pair-wise modelling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). This study is registered with PROSPERO (CRD42016050739). Findings: Our search identified 4876 studies, of which 114 were included in meta-analysis. Results identified several drug combinations with higher efficacy than single dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure 3.22, 95%CI 1.84-5.63; dERR 0.97, 95%CI 0.21-1.74), albendazole-oxantel pamoate (RR 5.07, 95%CI 1.65-15.59; dERR 0.51, 95%CI 0.450-0.52), mebendazole-ivermectin (RR 3.37, 95%CI 2.20-5.16), and tribendimidine-oxantel pamoate (RR 4.06, 95%CI 1.30-12.64). Interpretation: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against A. lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present. PMID- 29788075 TI - Effects of Immunonutrition in Advanced HIV Disease: a Randomized Placebo Controlled Clinical Trial (Promaltia Study). AB - Background: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in HIV-infected subjects initiating ART at advanced HIV disease remain unclear. Methodology: Pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T-cells/ul or AIDS were randomized to either daily PMT25341 (a mixture of prebiotics, probiotics, oligonutrients, DHA, EPA, GLA, and aminoacids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and microbiota composition (Clinicaltrials.gov: NCT00870363). Results: Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221108/ul and mean CD4/CD8 ratio of 0.260.19. PMT25341 was well tolerated; without grade 3 4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in median CD4+ T-cell count change (226 cells/ul vs. 414, P=0.461) or CD4/CD8 ratio change (0.21 vs. 0.48, P=0.854). Similarly, we did not detect differences between treatment arms in the variations of %HLADR+CD38+ or %CD28- T-cells, sCD14, LTA, IL-6, CRP, TNF-?, sCD163, IP-10, IL-7, IL-10, or IL-17 or alpha and beta microbiota diversity. Conclusion: In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the GALT and microbiota. PMID- 29788076 TI - Histological and Molecular Adipose Tissue Changes Are Related to Metabolic Syndrome Rather Than Lipodystrophy in Human Immunodeficiency Virus-Infected Patients: A Cross-Sectional Study. AB - Background: In human immunodeficiency virus (HIV)-infected patients on combination antiretroviral therapy (cART), lipodystrophy shares many similarities with metabolic syndrome, but only metabolic syndrome has objective classification criteria. We examined adipose tissue changes related to lipodystrophy and metabolic syndrome to clarify whether it may be acceptable to focus diagnosis on metabolic syndrome rather than lipodystrophy. Methods: This is a cross-sectional study of 60 HIV-infected men on cART and 15 healthy men. We evaluated lipodystrophy (clinical assessment) and metabolic syndrome (JIS-2009). We compared adipocyte size, leukocyte infiltration, and gene expression in abdominal subcutaneous adipose tissue biopsies of patients with and without lipodystrophy and with and without metabolic syndrome. Results: Lipodystrophy was only associated with increased macrophage infiltration (P = .04) and adiponectin messenger ribonucleic acid ([mRNA] P = .008), whereas metabolic syndrome was associated with larger adipocytes (P < .0001), decreased expression of genes related to adipogenesis and adipocyte function (P values between <.0001 and .08), increased leptin mRNA (P = .04), and a trend towards increased expression of inflammatory genes (P values between .08 and .6). Conclusions: Metabolic syndrome rather than lipodystrophy was associated with major unfavorable abdominal subcutaneous adipose tissue changes. In a clinical setting, it may be more relevant to focus on metabolic syndrome diagnosis in HIV-infected patients on cART with regards to adipose tissue dysfunction and risk of cardiometabolic complications. PMID- 29788078 TI - Reply. PMID- 29788077 TI - IRGM Gene Variants Modify the Relationship Between Visceral Adipose Tissue and NAFLD in Patients With Crohn's Disease. AB - Background: Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized comorbidity in Crohn's disease (CD), but the mechanisms are poorly understood. Autophagy is a highly conserved process regulating innate immunity that contributes to CD susceptibility. Emerging data suggest that variants in the autophagy-governing IRGM gene may contribute to the accumulation of visceral adipose tissue (VAT) and hepatic fat. Our objective was to characterize the relationship between VAT, IRGM gene variants, and NAFLD risk in patients with CD. Methods: We included all CD patients in the Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM) without history of alcohol abuse or liver disease. Hepatic fat was quantified by liver attenuation (LA) on computed tomography, with NAFLD defined by the validated liver:spleen (L:S) ratio. NAFLD severity was estimated by the FIB-4 Index and alanine aminotransferase (ALT). Using logistic regression modeling, we examined the relationship between VAT, autophagy gene variants, and NAFLD risk. Results: Among 462 patients, 52% had NAFLD. Increasing VAT quartile was associated with reduced LA (mean change, -7.43; 95% confidence interval [CI], -10.05 to -4.81; Ptrend < 0.0001). In the fully adjusted model, patients in the highest VAT quartile had a 2.2-fold increased NAFLD risk (95% CI, 1.21 to 4.14; Ptrend = 0.032) and a 4.2 fold increased risk of ALT>upper limit of normal (ULN) (95% CI, 1.19 to 14.76; Ptrend = 0.017). The relationship between VAT and NAFLD was modified by IRGM variants rs4958847 and rs13361189 (Pinteraction = 0.005 and Pinteraction < 0.001, respectively). Conclusions: In a large CD cohort, VAT was directly associated with prevalent NAFLD, and this relationship was augmented by functionally annotated IRGM variants associated with impaired autophagy. PMID- 29788079 TI - Long-Term Ambient Temperature and Externalizing Behaviors in Adolescents. AB - The climate-violence relationship has been debated for decades, and yet most of the supportive evidence has come from ecological or cross-sectional analyses with very limited long-term exposure data. We conducted an individual-level, longitudinal study to investigate the association between ambient temperature and externalizing behaviors of urban-dwelling adolescents. Participants (n = 1,287) in the Risk Factors for Antisocial Behavior Study, in California, were examined during 2000-2012 (aged 9-18 years) with repeated assessments of their externalizing behaviors (e.g., aggression, delinquency). Ambient temperature data were obtained from the local meteorological information system. In adjusted multilevel models, aggressive behaviors significantly increased with rising average temperatures (per 1 degrees C increment) in the preceding 1, 2, or 3 years (respectively, beta = 0.23, 95% confidence interval (CI): 0.00, 0.46; beta = 0.35, 95% CI: 0.06, 0.63; or beta = 0.41, 95% CI: 0.08, 0.74), equivalent to 1.5-3.0 years of delay in age-related behavioral maturation. These associations were slightly stronger among girls and families of lower socioeconomic status but greatly diminished in neighborhoods with more green space. No significant associations were found with delinquency. Our study provides the first individual level epidemiologic evidence supporting the adverse association of long-term ambient temperature and aggression. Similar approaches to studying meteorology and violent crime might further inform scientific debates on climate change and collective violence. PMID- 29788081 TI - Proteomic Characterization of the Extracellular Matrix of Human Uterine Fibroids. AB - Uterine leiomyomas (fibroids) are the most common benign tumors that are associated with increased production of extracellular matrix (ECM). Excessive ECM deposition plays a major role in the enlargement and stiffness of these tumors and contributes to clinical symptoms, such as abnormal bleeding and abdominal pain. However, no study so far has explored the global composition of the ECM of fibroids and normal myometrium. In this study, we performed a systematic ECM enrichment procedure and comparative proteomic analyses to profile the ECM composition of genetically annotated different-sized fibroids (small, medium, and large) and adjacent normal myometrium (ANM). Our matrisome analysis identified a combined total of 108, 126, 126, and 130 unique ECM and ECM-associated proteins with a confidence corresponding to a false discovery rate <1% in ANM and in small, medium, and large fibroids, respectively. The majority of fibroid ECM proteins belong to the core matrisome that includes glycoproteins, collagens, and proteoglycans. Considering that the small-sized fibroids represent the initial stages of leiomyogenesis, we highlighted some of the most abundant and important upregulated ECM proteins in small fibroids (i.e., POSTN, TNC, COL3A1, COL24A1, and ASPN). Furthermore, we revealed 30 unique ECM proteins that exist only in fibroids but that are not present in ANM regardless of MED12 mutation. We propose that some of the proteins identified represent potential novel ECM drug targets that may change the paradigm of fibroid treatment. PMID- 29788082 TI - Statistical testing against baseline in orthodontic research: a meta epidemiologic study. AB - Background/objectives: To assess the prevalence of within-group comparisons from baseline to follow-up in published orthodontic articles and to identify potential associations between this statistical problem and a number of study characteristics. Materials/method: The most recent 24 issues of four leading orthodontic journals with highest impact factor (American Journal of Orthodontics and Dentofacial Orthopedics; AJODO, European Journal of Orthodontics; EJO, Angle Orthodontist; ANGLE, Orthodontics and Craniofacial Research; OCR) were electronically searched until December 31st 2017. The proportion of articles using comparisons against baseline and interpretation of findings according to within-group comparisons were recorded. The association of this practice with journal, year of publication, study design, continent of authorship, number of centres and researchers, statistical significance of results, and statistical analysis was tested. Univariable and multivariable modified Poisson regression were used to identify significant predictors. Results: Overall, 339 articles were eligible for inclusion with the majority published in ANGLE (n = 157, 46%), followed by AJODO (n = 75, 22%), and EJO (n = 75, 22%). A total of 60 studies (18%) presented interpretation of their findings based on within-group comparisons against baseline in isolation. Statistical significance of the primary outcome was a very strong predictor of the prevalence of this flawed approach (RR: 2.33, 95% CIs: 1.22, 4.43; P = 0.01). Limitations: The effect of time since publication was not addressed. Conclusions/implications: Statistical testing and interpretation within groups is prevalent in orthodontic research. Endorsement of accurate conduct and reporting of statistical analyses and interpretation of research findings is important in order to promote optimal inferences to support clinical decision-making. PMID- 29788080 TI - Using Registry Data to Construct a Comparison Group for Programmatic Effectiveness Evaluation: The New York City HIV Care Coordination Program. AB - Many nonrandomized interventions rely upon a pre-post design to evaluate effectiveness. Such designs cannot account for events external to the intervention that may produce the outcome. We describe a method to construct a surveillance registry-based comparison group, which allows for estimating the effectiveness of the intervention while controlling for secular trends in the outcome of interest. Using data from the population-based, human immunodeficiency virus Surveillance Registry in New York City, we created a contemporaneous comparison group for persons enrolled in the New York City human immunodeficiency virus Care Coordination Program (CCP) from December 2009 to March 2013. Inclusion in the Registry-based (non-CCP) comparison group required meeting CCP eligibility criteria. To control for secular trends in the outcome, we randomly assigned persons in the non-CCP, Registry-based comparison group a pseudoenrollment date such that the distribution of pseudoenrollment dates matched the distribution of enrollment dates among CCP enrollees. We then matched CCP to non-CCP persons on propensity for enrollment in the CCP, enrollment dates, and baseline viral load. Registry-based comparison group estimates were attenuated relative to pre-post estimates of program effectiveness. These methods have broad applicability for observational intervention effectiveness studies and programmatic evaluations for conditions with surveillance registries. PMID- 29788083 TI - Evaluation of an Intensive Interdisciplinary Pain Treatment Based on Acceptance and Commitment Therapy for Adolescents With Chronic Pain and Their Parents: A Nonrandomized Clinical Trial. AB - Objective: Parental factors are central in the development and maintenance of chronic pain in youths. Only a handful of studies have investigated the impact of psychological treatments for pediatric chronic pain on parental factors, and the relationships between changes in parental and adolescent factors. In the current study, we evaluated the effects of an intensive interdisciplinary pain treatment (IIPT) program based on Acceptance and Commitment Therapy (ACT) for adolescents with chronic pain, on adolescent and parental variables, and the relationship between parental psychological flexibility and adolescent pain acceptance. Methods: Adolescents (N = 164) with chronic pain were included, with a mean age of 15.5 years, and completed the 3-week treatment with an accompanying parent (N = 164). Linear mixed-effects models were used to analyze change over time (from pretreatment to 3-month follow-up) on parent (depression, health-related quality of life and parent psychological flexibility) and adolescent (physical, social and emotional functioning, and adolescent pain acceptance) variables. Additionally, linear mixed-effects models were used to analyze the relationship between parent psychological flexibility and adolescent pain acceptance. Results: Results illustrated significant improvements over time in depressive symptoms and levels of psychological flexibility in parents. Excluding social development, adolescents improved significantly in all assessed aspects of functioning and pain acceptance. Additionally, changes in parent psychological flexibility were significantly associated with changes in adolescent pain acceptance. Conclusions: Results indicated that treatment had positive effects for parents and adolescents, and a significant positive relationship between changes in parent psychological flexibility and adolescent pain acceptance was found. PMID- 29788084 TI - Microbial activity during a coastal phytoplankton bloom on the Western Antarctic Peninsula in late summer. AB - Phytoplankton biomass during the austral summer is influenced by freezing and melting cycles as well as oceanographic processes that enable nutrient redistribution in the West Antarctic Peninsula (WAP). Microbial functional capabilities, metagenomic and metatranscriptomic activities as well as inorganic 13C- and 15N-assimilation rates were studied in the surface waters of Chile Bay during two contrasting summer periods in 2014. Concentrations of Chlorophyll a (Chla) varied from 0.3 mg m-3 in February to a maximum of 2.5 mg m-3 in March, together with a decrease in nutrients; however, nutrients were never depleted. The microbial community composition remained similar throughout both sampling periods; however, microbial abundance and activity changed with Chla levels. An increased biomass of Bacillariophyta, Haptophyceae and Cryptophyceae was observed along with night-grazing activity of Dinophyceae and ciliates (Alveolates). During high Chla conditions, HCO3- uptake rates during daytime incubations increased 5-fold (>2516 nmol C L-1 d-1), and increased photosynthetic transcript numbers that were mainly associated with cryptophytes; meanwhile night time NO3- (>706 nmol N L-1 d-1) and NH4+ (41.7 nmol N L-1 d-1) uptake rates were 2- and 3 fold higher, respectively, due to activity from Alpha-/Gammaproteobacteria and Bacteroidetes (Flavobacteriia). Due to a projected acceleration in climate change in the WAP, this information is valuable for predicting the composition and functional changes in Antarctic microbial communities. PMID- 29788085 TI - Involving young people in health promotion, research and policy-making: practical recommendations. AB - Youth is a dynamic and complex transition period in life where many factors jeopardise its present and future health. Youth involvement enables young people to influence processes and decisions that affect them, leading to changes in themselves and their environment (e.g. peers, services, communities and policies); this strategy could be applied to improve health and prevent diseases. Nonetheless, scientific evidence of involving youth in health-related programmes is scarce. The aim of this paper is to describe youth involvement as a health promotion strategy and to compile practical recommendations for health promoters, researchers and policy-makers interested in successful involvement of young people in health-related programmes. These suggestions aim to encourage a positive working synergy between adults and youth during the development, implementation and evaluation of policies, research and/or health promotion efforts that target adolescents. PMID- 29788086 TI - Prognostic ability of new T1 descriptors in the tumour, node and metastasis classification of surgically treated non-small-cell lung cancer. AB - OBJECTIVES: In the tumour, node and metastasis (TNM) classification (8th edition) of non-small-cell lung cancer, T (tumour size) is determined solely according to the size of the solid component determined using computed tomography (CT). However, it is unclear whether tumours of equal size but with differing solid and part-solid components should be similarly treated. Herein, we assessed the prognostic significance of the newly proposed T1 descriptors with respect to the size of the solid component. METHODS: We analysed overall survival (OS) and disease-free survival (DFS) between groups of patients (n = 255) with solid or part-solid tumours using propensity score matching. The new staging system was used for classification and comparison of survival. RESULTS: Chest CT detected 7 non-solid tumours, 123 part-solid tumours and 125 solid tumours. The 5-year OS and DFS rates differed significantly between the solid tumour (OS 71.2%; DFS 65.4%) and part-solid tumour (OS 83.2%; DFS 78.2%) groups. However, among 81 propensity score matching pairs (including those matched according to the size of the solid component), OS and DFS did not significantly differ between groups. The 5-year OS rates according to disease stage were as follows: cIA1 88.0%; cIA2 79.4% and cIA3 67.6%. CONCLUSIONS: Propensity score matching of solid tumour and part-solid tumour groups did not reveal a significant difference in survival as a function of the size of the solid component. A study of a larger cohort is required to validate this result. PMID- 29788087 TI - A Murine Frailty index based on Clinical and Laboratory Measurements: Links between Frailty and Pro-inflammatory Cytokines differ in a Sex-specific Manner. AB - A frailty index based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI Clinical scores and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 & 23-months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin-6, interleukin-9 and interferon gamma were associated with higher FI scores in aging females, while levels of interleukin-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally-aging mice differs between the sexes. PMID- 29788089 TI - The Relationship Between Traumatic Brain Injury and Rates of Chronic Symptomatic Illness in 202 Gulf War Veterans. AB - Introduction: Although not a "signature injury" of Operation Desert Shield/Desert Storm (i.e., Gulf War, GW), some GW veterans have a history traumatic brain injury (TBI). For example, a previous study found that 12.2% of the GW veterans from the Fort Devens Cohort Study had self-reported TBIs. The present study sought to build upon this finding by examining the relationship between TBI and chronic symptomatic illness in a different sample of GW veterans. Materials and Methods: Participants were 202 GW veterans recruited from 2014 to 2018 at the San Francisco Veterans Affairs Medical Center as part of a VA-funded study on the effects of predicted exposure to low levels of sarin and cyclosarin on brain structure and function. The Ohio State University TBI identification method was used to determine lifetime history of TBI. The Kansas Gulf War Military History and Health Questionnaire was used to assess symptoms and to determine cases of Kansas Gulf War Illness (GWI) and Centers for Disease Control and Prevention (CDC) Chronic Multisymptom Illness (CMI). Results: Nearly half (47%) the sample had a history of TBI, but only 7% of the TBIs were sustained in injuries that occurred during the GW. Most of the TBIs were sustained in injuries that occurred prior to (73%) or after (34%) the GW. History of TBI was not associated with higher rates of symptomatic illness when it was narrowly defined (i.e., Kansas GWI cases or cases of severe CMI). History of TBI was only associated with higher rates of symptomatic illness when it is broadly defined (i.e., CDC CMI or mild moderate CMI). There was suggestive evidence that veterans who sustained TBIs during the GW (only seven in the present sample) have poorer functional outcomes compared with GW veterans with non-GW related TBIs. Conclusions: While TBIs were uncommon during the GW, many GW veterans sustained TBIs prior or after the GW. Because TBI and GWI/CMI share some overlapping symptoms, history of TBI may appear to be associated with increased rates of chronic symptomatic illness in GW veterans if chronic symptomatic illness is defined broadly (i.e., CDC CMI or mild moderate CMI). History of pre-GW TBI did not affect the veterans' response to exposures/experiences from the GW; however, there was suggestive evidence that veterans who sustained TBIs during the GW may have poorer functional outcomes that GW veterans without TBI or even GW veterans with non-GW-related TBIs. Future, better powered studies with randomly and systematically select participants from the larger population of GW veterans will need to confirm this finding. PMID- 29788088 TI - Corrigendum to: Report: NIA Workshop on Measures of Physiologic Resiliencies in Human Aging. PMID- 29788090 TI - Disease Burden and Outcome in Children and Young Adults With Concurrent Graves Disease and Differentiated Thyroid Carcinoma. AB - Context: Adults with differentiated thyroid cancer (DTC) and Graves disease (GD) demonstrate a greater reported disease burden and aggressive DTC behavior. To date, no studies have examined the impact and long-term outcome of concurrent GD and DTC (GD-DTC) in children and young adults. Design: Single institution, retrospective longitudinal cohort study between 1997 and 2016. Participants: One hundred thirty-nine children and young adults with DTC, diagnosed at median age 15 (range, 5 to 23) years, compared with 12 patients with GD-DTC, median age 18 (range, 12 to 20) years. Major Outcome Measures: Patient demographics, preoperative imaging, fine needle aspiration (FNA) cytology, operative and pathological reports, laboratory studies, treatment, and subsequent 2-year outcomes. Results: Compared with DTC, patients with GD-DTC were significantly older at the time of DTC diagnosis (P < 0.01). Patients with GD-DTC were more likely to exhibit microcarcinoma (P < 0.01), and 2 of 12 (17%) demonstrated tall cell variant papillary thyroid cancer (PTC) vs 2 of 139 (2%) in patients who had DTC alone (P = 0.03). Although patients with DTC showed greater lymphovascular invasion (60% vs 25%; P = 0.03), no group differences were noted in extrathyroidal extension, regional lymph node, and distant or lung metastasis. There were no group differences in the 2-year outcome for remission, persistent disease, or recurrence. Conclusions: Concurrent DTC in pediatric patients with GD is not associated with a greater disease burden at presentation and shows no significant difference in 2-year outcomes compared with DTC alone. Similar to adults, microcarcinoma and tall cell variant PTC is prevalent in pediatric patients with GD-DTC. For patients who have GD-DTC with an identified nodule on ultrasound imaging prior to definitive therapy, FNA biopsy is recommended to guide definitive treatment. PMID- 29788091 TI - Determinants of incentive preferences for health behavior change in Japan. AB - Interest in the use of incentives to promote health behavior change has been growing worldwide. However, to develop an effective incentive program, accurate information regarding individual preferences is essential. Therefore, the aim of this study was to clarify determinants of incentive preferences for health behavior change. A self-completed questionnaire survey regarding incentives for health behavior change was conducted in a Japanese village in 2015. The outcome measures were individual preferences for features of incentives, including item, frequency, type and value. The types of incentives were defined as follows: assured-type (given for participation); effort-type (given if participants make some kind of effort); and outcome-type (given if participants make achievements decided a priori). The associations with respondents' sex, age, presence of lifestyle-related disease and stage in the transtheoretical model of health behavior change were investigated using multivariate analysis. A total of 1469 residents responded to the survey. Significant associations with preference for different incentive features were found as follows: for monetary items, female and elderly; for high frequency, female and maintenance stage; for effort-type, male, action stage and contemplation stage; and for outcome-type, maintenance stage and action stage. Our results appeared to identify determinants of incentive preferences for health behavior change. These findings are expected to promote the development of an incentive program more in tune with individual preferences. PMID- 29788092 TI - Cytokine IL9 Triggers the Pathogenesis of Inflammatory Bowel Disease Through the miR21-CLDN8 Pathway. AB - Background: Cytokine interleukin-9 (IL9) plays an essential role in the pathogenesis of inflammatory bowel disease. However, the molecular mechanism underlying the IL9 pathway remains unknown. Here, we initiate a series of studies to characterize the essential components of this pathway. Methods: The expression of IL9 in colon biopsies from Crohn's disease (CD) and controls were examined by quantitative polymerase chain reaction, immunoblot, and immunohistochemistry. The trinitrobenzene sulfonic acid (TNBS)-induced colitis model was used to verify the therapeutic efficiency of anti-IL9 mAb. Bioinformatics analysis was performed to predict putative candidate microRNAs that mediate the crosstalk between the IL9 proinflammatory signal and the downstream target gene in intestinal barrier function. Caco-2, NCM460, and SW480 cells were used to assess the specific pathway in vitro. Results: We demonstrated the proinflammatory role of IL9 in the colonic mucosa of patients with CD. The junction complex protein Claudin 8 (CLDN8) was identified as a critical downstream component of the IL9 inflammatory cascade. Anti-IL9 treatment alleviated TNBS-induced colitis by restoring CLDN8 levels in the colonic mucosa. Notably, we characterized miR21 as a critical player that mediates the crosstalk between the proinflammatory IL9 and the downstream CLDN8 in both in vitro and in vivo models. Conclusions: Our results, for the first time, uncover a critical role of miR21 and CLDN8 in the complex network that IL9 regulates the intestinal epithelium barrier in the pathogenesis of CD. Interventional blockade of the IL9-miR21-CLDN8 pathway could be a novel therapeutic approach for the management of CD. PMID- 29788093 TI - Reply to Buonfrate and Bisoffi. PMID- 29788094 TI - Risk Factors for Group A Streptococcus Colonization During an Outbreak Among People Experiencing Homelessness in Anchorage, Alaska, 2017. AB - We identified risk factors for any emm type group A streptococcal (GAS) colonization while investigating an invasive emm26.3 GAS outbreak among people experiencing homelessness in Alaska. Risk factors included upper extremity skin breakdown, sleeping outdoors, sharing blankets, and infrequent tooth brushing. Our results may help guide control efforts in future outbreaks. PMID- 29788096 TI - pNaKtide ameliorates renal interstitial fibrosis through inhibition of sodium potassium adenosine triphosphatase-mediated signaling pathways in unilateral ureteral obstruction mice. AB - Background: Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO. Methods: UUO was performed on male C57BL/6J mice. pNaKtide, a mimic of Na/K-ATPase, was administered by intraperitoneal injection on Day 0 and Day 4 after ureteral ligation. Markers of interstitial fibrosis, inflammation and oxidative stress and transforming growth factor-beta1 (TGF beta1) expression were examined after the mice were sacrificed on Day 7. Activation of Src and its downstream signaling effectors, including extracellular regulated protein kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase B (AKT), were evaluated. Results: pNaKtide administration markedly attenuated myofibroblast accumulation and extracellular matrix deposition in obstructed kidneys. Also, pNaKtide significantly reduced the increased expression of 8-iso-prostaglandin F2alpha, TGF-beta1, interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), as well as reduced macrophage infiltration, in UUO animals. All these changes were obtained, along with inhibition of Src and its downstream effector activity. Conclusions: Na/K-ATPase mediated signaling pathways contribute to fibrogenesis and could represent a potential target in the treatment of renal fibrosis. PMID- 29788097 TI - Hypertension treatment for older people-navigating between Scylla and Charybdis. AB - Hypertension is a common condition in older people, but is often one of many conditions, particularly in frail older people, and so is rarely managed in isolation in the real world-which belies the bulk of the evidence upon which is treatment decisions are often based. In this article, we discuss the issues of ageing, including frailty and dementia, and their impact upon blood pressure management. We examine the evidence base for managing hypertension in older people, and explore some therapeutic ideas that might influence treatment decisions and strategies, including shared decision making. PMID- 29788095 TI - Effects of maturity at harvest on the nutritive value and ruminal digestion of Eragrostis tef (cv. Moxie) when fed to beef cattle. AB - Teff (Eragrostis tef cv. Moxie), a warm-season annual grass, could be an excellent forage for beef cattle. However, there is limited information on its nutritive value to cattle when harvested at different stages of maturity. Thus, the objective of this research was to determine the effect of feeding teff hay harvested at the boot (BT), early-heading (EH), or late-heading (LH) stages of maturity on nutrient intake, ruminal fermentation characteristics, omasal nutrient flow, and N utilization in beef cattle. Six ruminally cannulated beef heifers (mean initial BW +/- SD, 476 +/- 32.6) were used in a replicated 3 * 3 Latin square design with 28-d periods (18 d for adaptation and 10 d for measurements). Dry matter intake was measured daily. Indwelling pH loggers were used to measure ruminal pH from days 21 to 28. Ruminal fluid and omasal digesta were collected from days 26 to 28 to determine fermentation characteristics and omasal nutrient flow. Fecal and urine samples to quantify N excretion were also collected (days 26 to 28). Blood samples for plasma urea-N (PUN) determination were collected 3 h post-feeding on day 28. There were no changes (P > 0.28) in the ADF or NDF content of teff with advancing maturity, but indigestible NDF increased (P < 0.01) with increasing maturity. Maturity had no effect (P >= 0.14) on DMI, and ruminal total short-chain fatty acid (SCFA) concentration, pH, digestibility, and outflow of DM, OM, NDF, ADF, and CP. However, the CP content of BT hay was greater (P < 0.01) than for EH and LH hay (18.1, 14.1, and 11.5%, respectively, DM basis), and this resulted in the higher CP intake (P < 0.01) for heifers fed the BT than the EH and LH hay. Consequently, ruminal ammonia-N (NH3 N) concentration was greater (P < 0.01) for heifers fed BT than EH and LH hay, thereby possibly explaining the tendency for a decrease (P = 0.08) in PUN concentration, and a decrease (P < 0.01) in the excretion of total N, urine N, and urea-N (UUN) with advancing maturity. However, fecal N excretion (g/d) did not differ (P = 0.76). In conclusion, despite a decrease in CP intake and ruminal NH3-N concentration, feeding beef heifers EH and LH compared to BT teff hay did not compromise ruminal digestion and outflow of DM, OM, NDF, ADF, and CP, and microbial protein synthesis. Advancing maturity in teff hay also resulted in a decrease in the excretion of total N and urine N and UUN when fed to cattle. PMID- 29788098 TI - Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance. AB - Background: Epidemiological studies have demonstrated an inverse association between Helicobacter pylori infection and the risk of developing inflammatory bowel disease (IBD). The mechanisms by which H. pylori infection protects against IBD are unclear. Here, we explored the possible protective effects and mechanisms of gastric H. pylori colonization on a chronic colitis model, with focus on whether H. pylori exerted its effects through regulating Th17/Treg immune responses. Methods: Chronic colitis was induced by dextran sulfate sodium (DSS) treatment. Flow cytometry analysis was performed to determine Th17 cells, Treg cells, and M1/M2 macrophages in the spleen, mesenteric lymph nodes, and colonic lamina propria. The levels of Th17- and Treg-associated cytokines were measured by quantitative polymerase chain reaction. The direct effect of H. pylori extract on the polarization status of macrophages was determined in vitro. Results: Gastric H. pylori colonization significantly ameliorated the severity of chronic DSS-induced colitis. H. pylori colonization decreased Th17 cells and mRNA levels of IL-17A, IL-17F, and IL-21 in the colon. Simultaneously, H. pylori colonization increased Treg cells and IL-10 expression. As to cytokines driving Th17 and Treg differentiation, H. pylori colonization increased TGFbeta and decreased IL-6 and IL-23. Moreover, H. pylori colonization significantly increased M2 macrophages in the colon. In vitro, H. pylori extract promotion of M2 macrophage polarization was dependent on the presence of CagA. Conclusions: H. pylori colonization protects against chronic DSS-induced colitis via balancing Th17/Treg responses and shifting macrophages toward anti-inflammatory M2 phenotype. Our results strengthen the rationale for gastric H. pylori colonization affecting the immune homeostasis of the colon. PMID- 29788099 TI - Biomarkers for Homologous Recombination Deficiency in Cancer. AB - Defective DNA repair is a common hallmark of cancer. Homologous recombination is a DNA repair pathway of clinical interest due to the sensitivity of homologous recombination-deficient cells to poly-ADP ribose polymerase (PARP) inhibitors. The measurement of homologous recombination deficiency (HRD) in cancer is therefore vital to the appropriate design of clinical trials incorporating PARP inhibitors. However, methods to identify HRD in tumors are varied and controversial. Understanding existing and new methods to measure HRD is important to their appropriate use in clinical trials and practice. The aim of this review is to summarize the biology and clinical validation of current methods to measure HRD, to aid decision-making for patient stratification and translational research in PARP inhibitor trials. We discuss the current clinical development of PARP inhibitors, along with established indicators for HRD such as germline BRCA1/2 mutation status and clinical response to platinum-based therapy. We then examine newer assays undergoing clinical validation, including 1) somatic mutations in homologous recombination genes, 2) "genomic scar" assays using array-based comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) analysis or mutational signatures derived from next-generation sequencing, 3) transcriptional profiles of HRD, and 4) phenotypic or functional assays of protein expression and localization. We highlight the strengths and weaknesses of each of these assays, for consideration during the design of studies involving PARP inhibitors. PMID- 29788101 TI - Left ventricular stroke volume in severe aortic stenosis and preserved left ventricular ejection fraction: prognostic relevance. PMID- 29788100 TI - A Cell-Based Approach to the Treatment of Inflammatory Bowel Disease-Entering an Era of Regenerative Medicine. AB - Corticosteroids, and more recently biologics, have been the mainstay of therapy for patients with inflammatory bowel disease. Unfortunately, both are fraught with side effects and limited by lack of efficacy or loss of response. Many patients ultimately succumb to medically refractory disease and require an operation. As we enter an era of regenerative medicine, a new genre of cell-based therapeutics offers significant promise for both an improved safety profile and improved efficacy compared with conventional treatment approaches. The ability to restore and rebuild health with autologous products rather than react to disease with pharmaceuticals gives hope to those who treat inflammatory bowel disease. The rationale and ongoing trials in an emerging field of medicine-regenerative medicine-is herein discussed. PMID- 29788102 TI - Legalization of Medicinal Marijuana Has Minimal Impact on Use Patterns in Patients With Inflammatory Bowel Disease. AB - Background: Patients with inflammatory bowel disease (IBD) have reported use of marijuana to treat symptoms of the disease, yet its classification as a Schedule 1 substance by the federal government has restricted its use. In 2012, Massachusetts legalized medicinal marijuana. We aimed to assess the impact of legalization on use in IBD. Methods: Consecutive patients with IBD, cared for at a tertiary care center in Boston, were surveyed regarding use of marijuana, including its perceived benefits and attitudes. Data were then compared with results of a similar survey study conducted at our center in 2012, before marijuana's legalization. Results: The survey was completed by 302 patients. There was a significant increase in marijuana use overall from 12.3% in 2012 to 22.8% in 2017 (P < 0.001). However, there was no significant increase in medicinal use from 2012 to 2017. On bivariate analysis, severe disease, as assessed by SIBDQ score, prior hospitalization, biologic therapy use, prior surgery, and chronic abdominal pain, was found to be more predictive of medicinal use now than in 2012. Among patients surveyed who have never used marijuana, 39.4% reported being interested in using medicinal marijuana, and 54.3% indicated that legalization did not affect their likelihood of using medicinal marijuana. Conclusions: In an IBD tertiary care center, we identified an overall upward trend in marijuana use but no significant change in medicinal use since its legalization in 2012. Our data suggests that the legalization of medical marijuana has resulted in an insignificant change in medicinal marijuana use in this population. 10.1093/ibd/izy141_video1izy141.video15786500236001. PMID- 29788103 TI - Post-ischaemic administration of the murine Canakinumab-surrogate antibody improves outcome in experimental stroke. AB - Aims: The CANTOS trial underscored the efficacy of selective antibody-based interleukin (IL)-1beta inhibition with Canakinumab in secondary prevention of cardiovascular events. Despite the success of the trial, incidence of stroke was not reduced likely due to the low number of events and the relatively young age of patients enrolled. Given the established role of IL-1beta in stroke, we tested the efficacy of the murine Canakinumab-equivalent antibody in a mouse model of ischaemic stroke. To mimic the clinical scenario of modern stroke management, IL 1beta inhibition was performed post-ischaemically upon reperfusion as it would be the case in patients presenting to the emergency room and eligible for thrombolytic therapy. Methods and results: Transient middle cerebral artery occlusion (tMCAO) was performed in wild type mice; upon reperfusion, mice were randomly allocated to anti-IL-1beta antibody or vehicle treatment. Following tMCAO, cerebral IL-1beta levels, unlike tumour necrosis factor-alpha, were increased underscoring a role for this cytokine. Post-ischaemic treatment with IL 1beta antibody reduced infarct size, cerebral oedema and improved neurological performance as assessed by 2,3,5-triphenyltetrazolium chloride staining, Bederson and RotaRod tests. Antibody-treated animals also exhibited a reduced neutrophil and matrix metalloproteinase (MMP)-2 but not MMP-9, activity in ipsilateral hemispheres as compared to vehicle-treated mice. Noteworthy, tMCAO associated vascular endothelial-cadherin reduction was blunted in IL-1beta antibody-treated mice compared to vehicle-treated, likely providing the mechanistic explanation for the improved outcome. Conclusion: Our data for the first time demonstrate the efficacy of selective post-ischaemic IL-1beta blockade in improving outcome following experimental ischaemia/reperfusion brain injury in the mouse and encourage further focused clinical studies assessing the potential of the approved IL-1beta antibody Canakinumab, as an adjuvant therapy to thrombolysis in acute ischaemic stroke patients. PMID- 29788104 TI - Erratum. PMID- 29788106 TI - Microsurgical Resection of a Solitary Spinal Epidural Cavernous Angioma: 3 Dimensional Operative Video. AB - Solitary spinal epidural cavernous angiomas are rare vascular malformations. Surgical excision is the treatment of choice, as these lesions tend to grow or bleed at some point. In this 3-dimensional, narrated video, we present the case of a 61-year-old male who presented with progressive pain in the right paravertebral region secondary to an epidural cavernous angioma located at the T6/T7 level. Under intraoperative neurophysiological monitoring, a laminectomy between T5 and T7 was performed. A reddish, well delimited, and highly vascularized epidural mass was identified and dissected from the adjacent dura and nerve root, and an en bloc total resection was achieved. The patient was discharged neurologically intact on postoperative day 4, presenting a remarkable improvement of his pain at 2-month follow-up. Total excision of these lesions is possible in most of cases, remaining the standard treatment, with minimum complications. All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All data related to patient identification were removed from this surgical video and manuscript, with no need of a written informed consent. PMID- 29788105 TI - Associations of Circulating 25-Hydroxyvitamin D3 Concentrations With Incident, Sporadic Colorectal Adenoma Risk According to Common Vitamin D-Binding Protein Isoforms. AB - Concentration of 25-hydroxyvitamin D3 (25(OH)D3), the main circulating form of vitamin D, is inversely associated with incident, sporadic colorectal adenoma risk. We investigated whether this association differs by 2 functional variants in the vitamin D-binding protein (DBP) gene, group-specific component (GC), that encode for common protein isoforms Gc1s, Gc1f, and Gc2 linked to differences in vitamin D metabolism. We pooled data (418 patients with adenoma and 524 polyp free control subjects) from 3 colonoscopy-based case-control studies (Minnesota, 1991-1994; North Carolina, 1994-1997; South Carolina, 2002). We estimated 25(OH)D3-adenoma associations, stratified by DBP isoforms, using multivariable logistic regression. Higher 25(OH)D3 concentrations were inversely associated with colorectal adenoma risk among those with the Gc2 isoform (per 10-ng/mL increase in 25(OH)D3, odds ratio = 0.71, 95% confidence interval: 0.56, 0.90), but not among those with only Gc1 isoforms (odds ratio = 1.07, 95% confidence interval: 0.87, 1.32; P for interaction = 0.03). Thus, the vitamin D-incident, sporadic colorectal adenoma association may differ by common DBP isoforms, and patients with the Gc2 isoform may particularly benefit from maintaining higher circulating 25(OH)D3 concentrations for adenoma prevention. PMID- 29788107 TI - N2 lung cancer is not all the same: an analysis of different prognostic groups. AB - OBJECTIVES: The International Association for the Study of Lung Cancer (IASLC) recently proposed a change in the staging system for N2, based on the metastatic station number: N2a1 (a single metastatic station with no hilar involvement), N2a2 (a single metastatic station with hilar involvement) and N2b (multiple metastatic stations). The aim of our study was to validate the IASLC proposal in a cohort of patients with pathological N2 disease. METHODS: All patients with pathological T1-T2 N2 non-small-cell lung cancer who were operated on between 2006 and 2010 in our department were enrolled. The patients had lobectomy, bilobectomy or pneumonectomy without induction therapy; patients with any type of extended resection were excluded. All patients had adjuvant treatment. The impact of the new IASLC proposal on the overall and disease-free survival rates was then analysed. RESULTS: Ninety-three patients were selected. The median follow-up period and overall survival time were 92 and 28.8 months, respectively. According to the new IASLC proposal, we observed 22 cases of N2a1, 54 N2a2 and 17 N2b. Patients with N2a1 had a significantly better overall survival than those with N2a2 and N2b (P = 0.041); the difference between N2a2 and N2b was not significant (P = 0.19). Patients with N2a1 squamous cell carcinoma had a significantly better overall survival than those with other histological diagnoses (P = 0.046). The disease-free interval was longer in patients with N2a1 than those in other groups (P = 0.021). CONCLUSIONS: Our experience partially validates the IASLC proposal; the introduction of quantitative criteria for N staging might improve stratification of patients and the assignment to the correct therapeutic path. PMID- 29788108 TI - Porphyromonas gingivalis strain dependent inhibition of uterine spiral artery remodeling in the pregnant rat. AB - Porphyromonas gingivalis (Pg), is an important periodontal pathogen that is also implicated in pregnancy complications involving defective deep placentation (DDP). We hypothesized that Pg invasion of the placental bed promotes DDP. Pregnant rats were intravenously inoculated with sterile vehicle, Pg strain W83, or A7436 at gestation day (GD) 14 (acute cohort). Non-pregnant rats received repeated oral inoculations for 3 months before breeding (chronic cohort). Tissues and/or sera were collected at GD18 for analysis. Pg infection status was determined by seroconversion (chronic cohort) and by presence of Pg antigen in utero-placental tissues processed for histology and morphometric assessment of spiral artery remodeling. Mesometrial tissues from seropositive dams were analyzed for expression of interleukin 1beta, 6, and 10, TNF, TGF-beta, follistatin-related protein 3, and inhibin beta A chain since these genes regulate extravillous trophoblast invasion. The in situ distribution of W83 and A7436 antigen in utero-placental tissues was similar in both cohorts. In the acute cohort, mesometrial stromal necrosis was more common with W83, but arteritis was more common with A7436 infection (P < 0.05). Increased vascular necrosis was seen in mesometrium of chronically infected groups (P < 0.05). Only A7436 infected animals had increased fetal deaths, reduced spiral artery remodeling, reduced inhibin beta A expression, and an increased proportion of FSLT3 positive extravillous trophoblasts within spiral arteries. While infection with both Pg strains produced varying pathology of the deep placental bed, only infection with strain A7436 resulted in impaired spiral artery remodeling. PMID- 29788109 TI - Primary graft failure after cardiac transplantation: prevalence, prognosis and risk factors. AB - OBJECTIVES: Primary graft failure (PGF) is a common and devastating complication, despite the advances in perioperative treatment. We aim to evaluate the prevalence of PGF and its impact on survival and to explore associated risk factors. METHODS: From November 2003 through December 2015, 290 patients submitted to cardiac transplantation were classified into non-PGF (243; 84%) and PGF (47; 16%) groups. The characteristics of the recipients were similar regarding age (54.6 +/- 10.6 vs 54.0 +/- 9.4 years; P = 0.74), male gender (78.2% vs 72.3%; P = 0.38) and transpulmonary gradient (9.4 +/- 4.2 vs 10.5 +/- 5.6 mmHg; P = 0.15); donors to the PGF group had similar age (35.5 +/- 11.4 vs 37.5 +/- 10.7 years; P = 0.27) but were predominantly female (21% vs 42.6%; P = 0.002). RESULTS: Mean ischaemic (89.0 +/- 36.8 vs 103.3 +/- 44.7 min; P = 0.019) and cardiopulmonary bypass (92.8 +/- 14.5 vs 126.3 +/- 62.4 min; P < 0.001) times were longer in the PGF group. Length of hospital stay was 13.5 +/- 7.5 vs 28.9 +/ 35.2 days (P= 0.005). Hospital mortality was 4.1% [1.6% for non-PGF and 17% for PGF (P < 0.001)]. Survival at 1, 5 and 10 years was 95.5 +/- 1.3% vs 55.3 +/- 7.3%, 84.1 +/- 2.5% vs 47.4 +/- 7.6% and 67.1 +/- 3.8% vs 14.4 +/- 12%, respectively (P < 0.001). Risk factors for PGF were female donor [odds ratio (OR): 2.56; 95% confidence interval (CI): 1.29-5.09; P = 0.007], total ischaemic time (OR: 1.01; 95% CI: 1.00-1.02; P = 0.032) and preoperative mechanical extracorporeal circulatory support (OR: 11.90; 95% CI: 2.62-54.12; P = 0.001). CONCLUSIONS: Our results demonstrate that PGF is associated with poor outcomes that extend beyond the 1st month and the 1st year after heart transplantation. We found female donor, total ischaemic time and preoperative mechanical extracorporeal circulatory support to be risk factors for PGF. PMID- 29788110 TI - Long-term compliance with a validated intravenous insulin therapy protocol in cardiac surgery patients: a quality improvement project. AB - Quality problem: Safe and efficient blood glucose (BG) level control after cardiac surgery relies on an intensive care unit (ICU) team-based approach, including implementation of a dynamic insulin therapy protocol (ITP). Long-term compliance with such a complex protocol is poorly addressed in the literature. The aim of this study was to assess the long-term compliance of nurses with the ITP, 7 years after its implementation in the ICU. Initial assessment: A professional practice evaluation, integrated in a process of quality improvement program, was retrospectively conducted on 224 consecutive cardiac surgery patients over a 6-month period (PHASE 1). The timing of BG measurements and the insulin infusion rate adjustments (primary endpoints) were correctly performed according to protocol requirements in 35 and 53% of the cases, respectively. Choice of solution and implementation: After systemic analysis of the causes of protocol deviations, four corrective measures aiming at improving both physician and nurse adherence to the protocol were implemented in the ICU. Evaluation: Evaluation of 104 patients in PHASE 2 showed a significant improvement in both the timing of BG measurements (83 %, P < 0.001 vs. PHASE 1), and insulin infusion rate adjustments (76%, P < 0.001). Lessons learned: Seven years after the implementation of a dynamic insulin infusion protocol, major protocol deviations were observed. Identification of several causes after a professional practice evaluation and the implementation of simple corrective measures restored a high level of nurse compliance. PMID- 29788111 TI - Acute Assessment of Traumatic Brain Injury and Post-Traumatic Stress After Exposure to a Deployment-Related Explosive Blast. AB - Introduction: Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are two of the signature injuries in military service members who have been exposed to explosive blasts during deployments to Iraq and Afghanistan. Acute stress disorder (ASD), which occurs within 2-30 d after trauma exposure, is a more immediate psychological reaction predictive of the later development of PTSD. Most previous studies have evaluated service members after their return from deployment, which is often months or years after the initial blast exposure. The current study is the first large study to collect psychological and neuropsychological data from active duty service members within a few days after blast exposure. Materials and Methods: Recruitment for blast-injured TBI patients occurred at the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq. Patients were referred from across the combat theater and evaluated as part of routine clinical assessment of psychiatric and neuropsychological symptoms after exposure to an explosive blast. Four measures of neuropsychological functioning were used: the Military Acute Concussion Evaluation (MACE); the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); the Headminder Cognitive Stability Index (CSI); and the Automated Neuropsychological Assessment Metrics, Version 4.0 (ANAM4). Three measures of combat exposure and psychological functioning were used: the Combat Experiences Scale (CES); the PTSD Checklist-Military Version (PCL-M); and the Acute Stress Disorder Scale (ASDS). Assessments were completed by a deployed clinical psychologist, clinical social worker, or mental health technician. Results: A total of 894 patients were evaluated. Data from 93 patients were removed from the data set for analysis because they experienced a head injury due to an event that was not an explosive blast (n = 84) or they were only assessed for psychiatric symptoms (n = 9). This resulted in a total of 801 blast-exposed patients for data analysis. Because data were collected in-theater for the initial purpose of clinical evaluation, sample size varied widely between measures, from 565 patients who completed the MACE to 154 who completed the CES. Bivariate correlations revealed that the majority of psychological measures were significantly correlated with each other (ps <= 0.01), neuropsychological measures were correlated with each other (ps <= 0.05), and psychological and neuropsychological measures were also correlated with each other (ps <= 0.05). Conclusions: This paper provides one of the first descriptions of psychological and neuropsychological functioning (and their inter-correlation) within days after blast exposure in a large sample of military personnel. Furthermore, this report describes the methodology used to gather data for the acute assessment of TBI, PTSD, and ASD after exposure to an explosive blast in the combat theater. Future analyses will examine the common and unique symptoms of TBI and PTSD, which will be instrumental in developing new assessment approaches and intervention strategies. PMID- 29788114 TI - Magnolol Inhibits Human Glioblastoma Cell Migration by Regulating N-Cadherin. AB - Glioblastoma is a primary malignant brain tumor with a poor prognosis. An effective treatment for glioblastoma is needed. Magnolol is a natural compound from Magnolia officinalis suggested to have antiproliferative activity. The aim of this research was to investigate the anticancer effects of magnolol in glioma, with an emphasis on migration and the underlying mechanism. Magnolol decreased the expression of focal adhesion-related proteins and inhibited LN229 and U87MG glioma cell migration. The levels of phosphorylated myosin light chain (p-MLC), phosphorylated myosin light chain kinase and myosin phosphatase target subunit 1 were reduced in response to magnolol treatment. In addition, immunostaining and membrane fractionation showed that the distribution of N-cadherin at the glioma cell membrane was decreased by magnolol. In an orthotropic xenograft animal model, magnolol treatment not only inhibited tumor progression but also reduced p MLC and N-cadherin protein expression. In conclusion, magnolol reduces cell migration, potentially through regulating focal adhesions and N-cadherin in glioma cells. Magnolol is a potential candidate for glioma treatment. PMID- 29788112 TI - Evolution of Gustatory Receptor Gene Family Provides Insights into Adaptation to Diverse Host Plants in Nymphalid Butterflies. AB - The host plant range of herbivorous insects is a major aspect of insect-plant interaction, but the genetic basis of host range expansion in insects is poorly understood. In butterflies, gustatory receptor genes (GRs) play important roles in host plant selection by ovipositing females. Since several studies have shown associations between the repertoire sizes of chemosensory gene families and the diversity of resource use, we hypothesized that the increase in the number of genes in the GR family is associated with host range expansion in butterflies. Here, we analyzed the evolutionary dynamics of GRs among related species, including the host generalist Vanessa cardui and three specialists. Although the increase of the GR repertoire itself was not observed, we found that the gene birth rate of GRs was the highest in the lineage leading to V. cardui compared with other specialist lineages. We also identified two taxon-specific subfamilies of GRs, characterized by frequent lineage-specific duplications and higher non synonymous substitution rates. Together, our results suggest that frequent gene duplications in GRs, which might be involved in the detection of plant secondary metabolites, were associated with host range expansion in the V. cardui lineage. These evolutionary patterns imply that the capability to perceive various compounds during host selection was favored during adaptation to diverse host plants. PMID- 29788115 TI - Neuropathology Education Using Social Media. AB - Social media use continues to grow among pathologists. Discussions of current topics, posts of educational information, and images of pathological entities are commonly found and distributed on popular sites such as Facebook and Twitter. However, little is known about the presence of neuropathology content in social media and the audience for such content. We designed and distributed a survey to assess the demographics of users viewing neuropathology content and their opinions about neuropathology in social media. User posts on the Facebook group, Surgical Neuropathology, were also analyzed. The results show that there is a demand for neuropathology content of high quality, curated by experts, and that this demand is present among both specialists and nonspecialists. These findings suggest that social media may be useful for rapid dissemination of information in the field of neuropathology. This format also offers a unique opportunity to extend the reach of information to nonneuropathologists who may not receive neuropathology journals or have access to specialty-level neuropathology training, to build networks between professionals, and potentially to influence public opinion of neuropathology on an international scale. PMID- 29788116 TI - American Association of Neuropathologists, Inc. Abstracts of the 94th Annual Meeting, June 7-10, 2018 Louisville, Kentucky. PMID- 29788113 TI - Differences in Performance among Test Statistics for Assessing Phylogenomic Model Adequacy. AB - Statistical phylogenetic analyses of genomic data depend on models of nucleotide or amino acid substitution. The adequacy of these substitution models can be assessed using a number of test statistics, allowing the model to be rejected when it is found to provide a poor description of the evolutionary process. A potentially valuable use of model-adequacy test statistics is to identify when data sets are likely to produce unreliable phylogenetic estimates, but their differences in performance are rarely explored. We performed a comprehensive simulation study to identify test statistics that are sensitive to some of the most commonly cited sources of phylogenetic estimation error. Our results show that, for many test statistics, traditional thresholds for assessing model adequacy can fail to reject the model when the phylogenetic inferences are inaccurate and imprecise. This is particularly problematic when analysing loci that have few informative sites. We propose new thresholds for assessing substitution model adequacy and demonstrate their effectiveness in analyses of three phylogenomic data sets. These thresholds lead to frequent rejection of the model for loci that yield topological inferences that are imprecise and are likely to be inaccurate. We also propose the use of a summary statistic that provides a practical assessment of overall model adequacy. Our approach offers a promising means of enhancing model choice in genome-scale data sets, potentially leading to improvements in the reliability of phylogenomic inference. PMID- 29788117 TI - Are we ready to improve phosphorus homeostasis in rice? AB - Phosphorus (P) is an essential macronutrient which often limits plant growth, but the phosphate rock used for fertilizer production is a finite resource. On the other hand, large amounts of P compounds are entering surface waters, leading to eutrophication. Therefore, improvement of phosphate use efficiency of crop plants is a major task for plant science. Rice as a staple crop has recently been a focus of such efforts with several major discoveries. New transporters controlling phosphate homeostasis in rice have been discovered. Manipulation of expression of the corresponding genes improves different components of phosphate use efficiency, such as delivery of phosphate to the developing seeds and synthesis of phytic acid. Here these new findings are discussed in the context of general P nutrition and with the aim of finding out how far we can optimize P homeostasis in rice. PMID- 29788118 TI - Risk Factors for Treatment Failure and Mortality among Hospitalised Patients with Complicated Urinary Tract Infection: A Multicentre Retrospective Cohort Study, RESCUING Study Group. AB - Background: Complicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among hospitalised patients with cUTIs. Methods: A multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients' files on hospitalised patients with a diagnosis of cUTI during 2013 2014. The primary outcome was treatment failure. Secondary outcomes included all cause mortality 30 days, among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for treatment failure and 30 day mortality. Results: A total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981) of patients; all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis, were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95% C: 1.4-3.18), older age (OR 1.02 for 1 year, 95% CI 1.007-1.03), metastatic cancer (OR 2.89, 95% CI 1.46 5.73), and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171 (64.3%) vs. 116/270 (43%), p<0.005], nevertheless, appropriate empirical antibiotic treatment afforded no advantage in treatment failure rates nor in 30-day mortality in these patients. Conclusions: In patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined. PMID- 29788120 TI - Immediate hypersensitivity to bee pollen granules. PMID- 29788119 TI - The effects of leptin on plasma concentrations of prolactin, growth hormone, and melatonin vary depending on the stage of pregnancy in sheep. AB - The effects of hyperleptinemia and leptin resistance during gestation are unclear. Leptin, an important neuroendocrine regulator, has anorexic effects, but its interactions with other metabolic hormones during pregnancy are unclear. We examined potential roles of leptin in regulating prolactin (PRL), GH, and melatonin plasma concentrations during pregnancy in Polish Longwool ewes. Twelve estrus-synchronized ewes carrying twins after mating were randomly assigned to receive i.v. injections of saline or recombinant ovine leptin (2.5 or 5.0 ug/kg BW). Blood samples were collected (15-min intervals over 4 h) immediately before the first injection at dusk and kept under red light. Treatments were repeated at 2-wk intervals, starting before mating and continuing from days 30 to 135 of gestation. Concentrations of plasma PRL, GH, and melatonin were determined using a validated RIA. The effects of leptin on hormone plasma concentrations varied depending on pregnancy stage and leptin dose. PRL plasma concentrations were affected at most stages of pregnancy and before gestation. In non-, very early- (day 30), and late- (day 120 and 135) pregnant ewes, exogenous leptin stimulated PRL (P < 0.001) plasma concentrations, while during the second month of gestation, it decreased PRL concentrations (P < 0.01). Leptin affected GH plasma concentrations (P < 0.05) only during the first 2 mo of pregnancy, with no effects during the second part of gestation or before pregnancy. In early pregnant ewes (day 30 and 45), leptin decreased melatonin plasma concentrations (P < 0.05), but at day 60, leptin stimulated melatonin plasma concentrations at low (P < 0.01) and high doses (P < 0.05), with no effects in ewes after 105 d of gestation. These data indicate specific pregnancy-induced endocrine adaptations to changes in energy homeostasis, supporting the hypothesis that leptin affects PRL, GH, and melatonin release during gestation. PMID- 29788121 TI - Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging. AB - Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time. Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged >=50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA). Plasma metabolites were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates). Results: Of 148 plasma metabolites (amino acids, biogenic amines, hexoses, glycerophospholipids) measured, eight were significantly associated with gait speed at baseline, independent of age and sex: hexoses (r = -0.148, p < .001), [sphingomyelin (SM) 16:1 (r = -0.091, p = .0009), SM 18:0 (r = -0.085, p = .002), SM 18:1 (r = -0.128, p < .0001], phosphatidylcholine aa 32:3 (r = -0.088, p = .001), lysophosphatidylcholine (LPC) 17:0 (r = 0.083, p = .003), LPC 18:1 (r = 0.089, p = .001), and LPC 18:2 (r = 0.104, p < .0001). Adjusting for baseline age, sex, and chronic diseases, baseline plasma LPC 18:2 was an independent predictor of the rate of change of gait speed over subsequent follow-up (p = .003). No other plasma metabolites were significantly associated longitudinal changes of gait speed over time. Conclusions: Low plasma LPC 18:2, which has previously been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment, is an independent predictor of decline in gait speed in older adults. PMID- 29788122 TI - Viewpoint: Toward the Genetic Architecture of Disease Severity in Inflammatory Bowel Diseases. AB - Inflammatory bowel disease (IBD) is characterized by uneven disease courses with various clinical outcomes. A few prognostic markers of disease severity may help stratify patients and identify those who will benefit the most from early aggressive treatment. The concept of disease severity remains too broad and vague, mainly because the definition must embrace several disease mechanisms, mainly inflammation and fibrosis, with various rates of disease progression. The magnitude of inflammation is an obvious key driver of disease severity in IBD that ultimately influence disease behavior. Advances in the genetics underlying disease severity are currently emerging, but attempts to overlap the genetics of disease susceptibility and severity have until now been unsatisfactory, suggesting that the genetic architecture of disease severity may be distinct from the genetics of disease susceptibility. In this review, we report on the current knowledge on disease severity and on the main research venues to decipher the genetic architecture of disease severity. PMID- 29788123 TI - Gastric Emptying and the Personalized Management of Type 1 Diabetes. PMID- 29788124 TI - Type I secretion system-it takes three and a substrate. AB - Type I secretion systems are widespread in Gram-negative bacteria and mediate the one-step translocation of a large variety of proteins serving for diverse purposes, including nutrient acquisition or bacterial virulence. Common to most substrates of type I secretion systems is the presence of a C-terminal secretion sequence that is not cleaved during or after translocation. Furthermore, these protein secretion nanomachineries are always composed of an ABC transporter, a membrane fusion protein, both located in the inner bacterial membrane, and a protein of the outer membrane. These three membrane proteins transiently form a 'tunnel channel' across the periplasmic space in the presence of the substrate. Here we summarize the recent findings with respect to structure, function and application of type I secretion systems. PMID- 29788125 TI - Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis. AB - There has been a significant reduction in annual tuberculosis incidence since the World Health Organization declared tuberculosis a global health threat. However, treatment of M. tuberculosis infections requires lengthy multidrug therapeutic regimens to achieve a durable cure. The development of new drugs that are active against resistant strains and phenotypically diverse organisms continues to present the greatest challenge in the future. Numerous phylogenomic analyses have revealed that the Mtb genome encodes a significantly expanded repertoire of toxin antitoxin (TA) loci that makes up the Mtb TA system. A TA loci is a two-gene operon encoding a 'toxin' protein that inhibits bacterial growth and an interacting 'antitoxin' partner that neutralizes the inhibitory activity of the toxin. The presence of multiple chromosomally encoded TA loci in Mtb raises important questions in regard to expansion, regulation and function. Thus, the functional roles of TA loci in Mtb pathogenesis have received considerable attention over the last decade. The cumulative results indicate that they are involved in regulating adaptive responses to stresses associated with the host environment and drug treatment. Here we review the TA families encoded in Mtb, discuss the duplication of TA loci in Mtb, regulatory mechanism of TA loci, and phenotypic heterogeneity and pathogenesis. PMID- 29788127 TI - Herpes Zoster in Patients Receiving JAK Inhibitors For Ulcerative Colitis: Mechanism, Epidemiology, Management, and Prevention. AB - Increased risk of herpes zoster (HZ) has been observed in patients with immune mediated diseases, including rheumatoid arthritis (RA), psoriasis (PsO), and inflammatory bowel disease; this risk can be further increased by the use of immunosuppressive therapy. One advancing modality of therapy for these diseases is Janus kinase (JAK) inhibition. Tofacitinib is an oral JAK inhibitor for the treatment of RA and psoriatic arthritis, which is currently under investigation for the treatment of ulcerative colitis (UC) and was previously investigated for psoriasis. JAK inhibitors have been associated with HZ events in patients across a number of indications. The pathogenesis underlying this risk of HZ is currently unknown. An increased risk of HZ has been noted in patients receiving immunosuppressive therapies for UC, including tofacitinib. In clinical trials, there was a dose-dependent risk of HZ (higher dose linked with increased risk). However, the majority of HZ cases are nonserious and noncomplicated, mild to moderate in severity, and manageable without permanent discontinuation of treatment. This review will discuss HZ risk in patients receiving JAK inhibitors, focusing on tofacitinib with respect to the potential mechanisms and epidemiology of HZ. Current guidelines for the prevention of HZ will be highlighted, and proposed management reviewed. PMID- 29788126 TI - Characterizing the acute heat stress response in gilts: II. Assessing repeatability and association with fertility. AB - Mitigating heat stress (HS) in swine production is important as it detrimentally affects multiple aspects of overall animal production efficiency. Study objectives were to determine if gilts characterized as tolerant (TOL) or susceptible (SUS) in response to HS maintain that phenotype later in life and if that phenotype influences reproductive ability during HS. Individual gilts identified as TOL (n = 50) or SUS (n = 50) from a prepubertal HS challenge were selected based on their rectal temperature (TR) during acute HS. The study consisted of 4 experimental periods (P). During P0 (2 d), all pigs were exposed to thermoneutral (TN) conditions (21.1 degrees C). During P1 (14 d), all gilts received Matrix (15 mg altrenogest per day) to synchronize estrus, and were maintained in TN conditions. During P2 (9 d), Matrix supplementation was terminated and gilts were subjected to diurnal HS with ambient temperatures set at 35 degrees C from 1000 to 2200 h and 21 degrees C from 2200 to 1000 h. Also during P2 gilts underwent estrus detection and artificial insemination. During P3 gilts were housed in TN conditions for 41 d at which they were sacrificed and reproductive tracts were collected. During the last 2 d of P1 and throughout the entirety of P2, TR and skin temperature (TS) were recorded. During P2, SUS had increased TR relative to TOL pigs during P2 (0.27 degrees C; P < 0.01). Overall, uterine wet weight, ovarian weight, corpora lutea (CL) count, and embryo survival were 5.6 +/- 0.1 kg, 21.6 +/- 0.3 g, 17.8 +/- 0.3 CLs, and 79 +/- 2%, respectively, and not influenced by prepubertal HS tolerance classification (P >= 0.37). Tolerant gilts had a longer return-to-estrus (6.1 vs. 5.5 d, respectively; P = 0.01) following altrenogest withdrawal and tended to have larger CL diameters (10.3 vs. 10.1 mm; P = 0.06) compared to SUS gilts. Fetal weight (25.4 vs. 23.6 g; P = 0.01) and fetal crown-rump length (74.8 vs. 72.8 mm; P < 0.01) were higher in gilts previously classified as SUS compared to those previously classified as TOL. Additionally, neither litter size nor the number of fetuses detected as a percentage of ovulations was influenced by classification. In summary, SUS gilts had a shorter return-to-estrus, increased fetus size, and tended to have smaller CL diameters compared to TOL gilts. Additionally, SUS gilts also retained their inability to maintain euthermia postpubertally relative to TOL gilts. In conclusion, there appeared to be little reproductive advantage of maintaining a lower TR during HS. PMID- 29788128 TI - Sleep Patterns and Problems Among Army National Guard Soldiers. AB - Introduction: Adequate sleep plays an integral role in the physical and mental health of individuals, while simultaneously influencing their cognitive and work performance. Having recognized this, the U.S. Army has focused efforts on improving soldiers' healthy sleep behaviors. This study examines the extent to which mental health, alcohol use, and certain sleep hygiene behaviors predict sleep problems within an Army National Guard sample (N = 438). Materials and Methods: This manuscript is part of a larger study approved through the Minneapolis Veterans Affairs Medical Center Institutional Review Board. Mailed surveys were sent to Minnesota Army National Guard soldiers collecting data on sleep hygiene behaviors, mental health symptoms (post-traumatic stress disorder and depression), and alcohol use. Predictors of sleep problems were evaluated with ordinary least squares multiple linear regression analyses, regressing Insomnia Severity Index total scores on demographic variables, post-traumatic stress disorder (PTSD), depression, alcohol use, sleep hygiene factors (routine and consumption activity; both derived from exploratory factor analysis), and technology use (multiple device use and use before bed). Results: Overall, the majority of participants did not endorse high levels of sleep impairment, while 16.4% screened positive for moderate or even severe levels of clinical insomnia. Bivariate correlations demonstrated that sleep problems were correlated with PTSD symptoms (r = 0.41, p < 0.001), depression (r = 0.49, p < 0.001), Sleep Hygiene Routine (r = -0.34, p < 0.001), and more frequent use of multiple devices before bed (r = 0.15, p = 0.002). The overall regression model predicting sleep problems was significant (R2 = 0.35, adj R2 = 0.34, F[8,408] = 27.58, p < 0.001). Independent predictors of sleep problems included gender (B = 0.99, beta = 0.09, t = 2.10, p = 0.036), PTSD (B = 0.89, beta = 0.22, t = 4.86, p < 0.001), depression (B = 1.53, beta = 0.20, t = 7.56, p < 0.001), and Sleep Hygiene Routine (B = -0.88, beta = -0.23, t = -5.473, p < 0.001). Alcohol use, Sleep Hygiene Consumption, and technology use did not emerge as independent predictors. Conclusion: Although most soldiers denied sleep problems, a sizeable minority met screening criteria for clinical insomnia. Greater numbers of sleep-related complaints were related to psychological distress including depressive and PTSD symptoms, while adherence to a bedtime routine (Sleep Hygiene Routine) showed an inverse relationship. Alcohol use and sleep hygiene consumption activities were not predictive of sleep problems, suggesting that different sleep hygiene behaviors have differential relationships with sleep problems. Screening and intervention for specific sleep problems may be helpful even very early in Army National Guard service members' careers. Particular focus may be needed for those showing signs of emotional distress, such as PTSD or depression. Future research examining the impact of individual sleep hygiene components is warranted. PMID- 29788129 TI - mTM-align: a server for fast protein structure database search and multiple protein structure alignment. AB - With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop algorithms for efficient protein structure comparisons. In this article, we present the mTM-align server, which consists of two closely related modules: one for structure database search and the other for multiple structure alignment. The database search is speeded up based on a heuristic algorithm and a hierarchical organization of the structures in the database. The multiple structure alignment is performed using the recently developed algorithm mTM-align. Benchmark tests demonstrate that our algorithms outperform other peering methods for both modules, in terms of speed and accuracy. One of the unique features for the server is the interplay between database search and multiple structure alignment. The server provides service not only for performing fast database search, but also for making accurate multiple structure alignment with the structures found by the search. For the database search, it takes about 2-5 min for a structure of a medium size (~300 residues). For the multiple structure alignment, it takes a few seconds for ~10 structures of medium sizes. The server is freely available at: http://yanglab.nankai.edu.cn/mTM-align/. PMID- 29788130 TI - Patient Barriers and Facilitators to Ambulatory and Home Blood Pressure Monitoring: A Qualitative Study. AB - BACKGROUND: Guidelines recommend that patients with newly elevated office blood pressure undergo ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) to rule-out white coat hypertension before being diagnosed with hypertension. We explored patients' perspectives of the barriers and facilitators to undergoing ABPM or HBPM. METHODS: Focus groups were conducted with twenty English- and Spanish-speaking individuals from underserved communities in New York City. Two researchers analyzed transcripts using a conventional content analysis to identify barriers and facilitators to participation in ABPM and HBPM. RESULTS: Participants described favorable attitudes toward testing including readily understanding white coat hypertension, agreeing with the rationale for out-of-office testing, and believing that testing would benefit patients. Regarding ABPM, participants expressed concerns over the representativeness of the day the test was performed and the intrusiveness of the frequent readings. Regarding HBPM, participants expressed concerns over the validity of the monitoring method and the reliability of home blood pressure devices. For both tests, participants noted that out-of-pocket costs may deter patient participation and felt that patients would require detailed information about the test itself before deciding to participate. Participants overwhelmingly believed that out-of-office testing benefits outweighed testing barriers, were confident that they could successfully complete either testing if recommended by their provider, and described the rationale for their testing preference. CONCLUSIONS: Participants identified dominant barriers and facilitators to ABPM and HBPM testing, articulated testing preferences, and believed that they could successfully complete out-of-office testing if recommended by their provider. PMID- 29788131 TI - Is Ivermectin Ineffective for Strongyloidiasis? PMID- 29788134 TI - Novel Insights Into the Impact of Lifestyle-Based Weight Loss and Metformin on Obesity-Associated Biomarkers in Breast Cancer. PMID- 29788133 TI - Randomized Trial of a Group Music and Imagery Method (GrpMI) for Women with Fibromyalgia. AB - Background: Fibromyalgia (FM) affects about 2-4% of the world population. Patients, mostly women, experience chronic widespread pain, fatigue, stiffness, sleep disturbances, and psychological disorders, especially depression and anxiety. Objective: The aim of this study was to examine preliminary efficacy of a Group Music and Imagery (GrpMI) intervention, which included relaxation, music listening, and spontaneous imagery, to improve subjective psychological well being, functional capacity and health, pain perception, anxiety, and depression in women with FM. Methods: Fifty-six women aged 35 to 65 years (M = 51.3) diagnosed with FM were randomly assigned to either GrpMI treatment (n = 33) or control (n = 26) condition. Experimental group participants received 12 weekly GrpMI sessions, and control group participants who did not receive any additional service completed measures at the same time points as the experimental group. Results: Intra-group analyses showed that GrpMI participants had a significant increase in psychological well-being and significant decrease in the impact of FM on functional capacity and health, pain perception, anxiety, and depression post treatment, with sustained benefit at three-month follow-up for all variables except psychological well-being. Control group participants showed decreases in trait anxiety and depression at post-treatment, with no significant benefit at three-month follow-up. Inter-group analyses showed that compared with control participants, GRpMI participants had significantly higher scores for psychological well-being and lower-state anxiety post-treatment; however, no differences were observed between groups at three-month follow-up. Conclusions: Findings offer preliminary evidence for the benefit of GrpMI to improve well being and reduce anxiety in women with FM. Findings also suggest that GrpMI may help diminish pain intensity, state depression, and the impact of FM on functional capacity and health, but further studies are needed to establish efficacy. PMID- 29788132 TI - Freiburg RNA tools: a central online resource for RNA-focused research and teaching. AB - The Freiburg RNA tools webserver is a well established online resource for RNA focused research. It provides a unified user interface and comprehensive result visualization for efficient command line tools. The webserver includes RNA-RNA interaction prediction (IntaRNA, CopraRNA, metaMIR), sRNA homology search (GLASSgo), sequence-structure alignments (LocARNA, MARNA, CARNA, ExpaRNA), CRISPR repeat classification (CRISPRmap), sequence design (antaRNA, INFO-RNA, SECISDesign), structure aberration evaluation of point mutations (RaSE), and RNA/protein-family models visualization (CMV), and other methods. Open education resources offer interactive visualizations of RNA structure and RNA-RNA interaction prediction as well as basic and advanced sequence alignment algorithms. The services are freely available at http://rna.informatik.uni freiburg.de. PMID- 29788135 TI - The Hepatic Glucocorticoid Receptor Is Crucial for Cortisol Homeostasis and Sepsis Survival in Humans and Male Mice. AB - Sepsis is hallmarked by hypercortisolemia, a stress response essential for survival. This elevation in plasma cortisol is partially brought about by suppressed hepatic cortisol breakdown. We demonstrate that a controlled downregulation of the hepatic glucocorticoid receptor (hepatic GR) is crucial. In a mouse model of fluid-resuscitated, antibiotic-treated abdominal sepsis and in human intensive care unit patients, sepsis reduced hepatic GR expression and signaling but increased (free) plasma cortisol/corticosterone, explained by suppressed cortisol/corticosterone-binding proteins and A-ring reductases. However, further experimental inhibition of hepatic GR with short hairpin RNA (shRNA) in septic mice increased mortality fivefold. Acutely, this further hepatic GR suppression prevented the rise in total corticosterone but further reduced binding proteins, resulting in elevated free corticosterone. After 3 days of shRNA-GR inhibition in sepsis, both total and free corticosterone levels were elevated, now explained by an additional reduction in A-ring reductase expression. Hepatic GR inhibition blunted the hyperglycemic stress response without causing hypoglycemia but also markedly increased circulating and hepatic inflammation markers and caused liver destruction, the severity of which explained increased mortality. In human sepsis, glucocorticoid treatment further suppressed hepatic GR expression, which could directly predispose to worse outcomes. In conclusion, sepsis partially suppressed hepatic GR expression, which appeared crucial to upregulate free cortisol/corticosterone availability. However, further sustained hepatic GR suppression evoked lethal excessive liver and systemic inflammation, independent of systemic cortisol/corticosterone availability. PMID- 29788136 TI - An experimental evaluation of the benefits and costs of providing fertility information to adolescents and emerging adults. AB - STUDY QUESTION: Does the provision of fertility (compared to control) information affect fertility-related knowledge, perceived threat of infertility, anxiety, physical stress and fertility plans in adolescents and emerging adults? SUMMARY ANSWER: The provision of fertility information was associated with increased fertility knowledge (emerging adults) and greater infertility threat (adolescents and emerging adults). WHAT IS KNOWN ALREADY: According to fertility education research, adolescents and emerging adults know less than they should know about fertility topics. Fertility knowledge can be improved through the provision of information in older adults. STUDY DESIGN, SIZE, DURATION: Experimental design. Secondary and university students completed pre-information questionnaires, were randomly assigned via computer to an experimental group, read either fertility (FertiEduc group) or healthy pregnancy information (Control group), and completed post-information questionnaires. Data were collected in group sessions via an online portal. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible participants were aged 16-18 (adolescents) or 21-24 years (emerging adults), childless, not currently pregnant (for men, partner not pregnant) or trying to conceive, presumed fertile and intending to have a child in the future. Of the 255 invited, 208 (n = 93 adolescents, n = 115 emerging adults) participated. The FertiEduc group received 'A Guide to Fertility', four online pages of information about fertility topics (e.g. 'When are men and women most fertile?') and the Control group received four online pages from the National Health Service (NHS) pregnancy booklet 'Baby Bump and Beyond'. Participants completed a questionnaire (fertility knowledge, perceived threat of infertility, anxiety, physical stress and fertility plans, moderators) prior to and after the provision of information. Mixed factorial analysis of variance was used to examine the effects of information provision and hierarchical multiple regression to assess potential moderators of knowledge. MAIN RESULTS AND THE ROLE OF CHANCE: The FertiEduc and Control groups were equivalent on age, gender, disability, relationship status and orientation at baseline. Results showed that fertility information significantly increased fertility knowledge for emerging adults only (P < 0.001) and threat of infertility for emerging adults and adolescents (P = 0.05). The moderators were not significant. Participation in the study was associated with an increase in feelings of anxiety but a decrease in physical stress reactions. Adolescents had more optimal fertility plans compared to emerging adults due to being younger. LIMITATIONS, REASONS FOR CAUTION: This was an experimental study on a self-selected sample of men and women from selected educational institutions and only short term effects of information were studied. WIDER IMPLICATIONS OF THE FINDINGS: Provision of fertility information can have benefits (increased fertility knowledge) but also costs (increase potential threat of infertility). Adolescents find fertility information positive but do not learn from it. Fertility education should be tailored according to age groups and created to minimise negative effects. Longitudinal examination of the effects of fertility information in multi-centre studies is warranted and should include measures of perceived threat of infertility. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded this research. All authors have no conflicts of interest to declare. PMID- 29788137 TI - Inflammatory Bowel Disease Telemedicine Clinical Trial: Impact of Educational Text Messages on Disease-Specific Knowledge Over 1 Year. AB - Background: Effective treatments are available for patients with inflammatory bowel disease (IBD); however, suboptimal outcomes occur and are often linked to patients' limited disease knowledge. The aim of this analysis was to determine if delivery of educational messages through a telemedicine system improves IBD knowledge. Methods: TELEmedicine for Patients with IBD (TELE-IBD) was a randomized controlled trial with visits at baseline, 6 months, and 12 months; patient knowledge was a secondary aim of the study. Patients were randomized to receive TELE-IBD every other week (EOW), weekly (TELE-IBD W), or standard of care. Knowledge was assessed at each visit with the Crohn's and Colitis Knowledge (CCKNOW) survey. The primary outcome was change in CCKNOW score over 1 year compared between the TELE-IBD and control groups. Results: This analysis included 219 participants. Participants in the TELE-IBD arms had a greater improvement in CCKNOW score compared with standard care (TELE-IBD EOW +2.4 vs standard care +1.8, P = 0.03; TELE-IBD W +2.0 vs standard care +1.8, P = 0.35). Participants with lower baseline CCKNOW scores had a greater change in their score over time (P < 0.01). However, after adjusting for race, site, and baseline knowledge, there was no difference in CCKNOW score change between the control and telemedicine arms. Conclusions: Telemedicine improves IBD-specific knowledge through text messaging, although the improvement is not additive with greater frequency of text messages. However, after adjustment for confounding variables, telemedicine is not superior to education given through standard visits at referral centers. Further research is needed to determine if revised systems with different modes of delivery and/or frequency of messages improve disease knowledge. PMID- 29788138 TI - Gram-negative bacilli are a major cause of secondary pneumonia in patients with pulmonary tuberculosis: evidence from a cross-sectional study in a tertiary hospital in Nigeria. AB - Background: This study was aimed at describing the profile of bacterial aetiology of secondary pneumonia in pulmonary tuberculosis (PTB) patients. Methods: A 22 month analysis of patients with PTB and secondary bacterial pneumonia was conducted. Data on isolates recovered and the antimicrobial susceptibility profile were recorded. Results: Of the 141 patients, there were 79 (56%) males and the mean age was 35.98+/-15.93. Gram-negative bacilli were isolated with equal frequency as Streptococcus pneumoniae (63 [44.7%]). Most of the isolates tested were sensitive to levofloxacin, ceftriaxone or chloramphenicol. Conclusion: Gram-negative bacilli are a major cause of pneumonia in patients with PTB on treatment. PMID- 29788139 TI - Microsurgical Resection of Spinal Cord Hemangioblastoma: 2-Dimensional Operative Video. AB - This video demonstrates microsurgical resection of spinal cord hemangioblastoma. Hemangioblastomas are rare, benign, highly vascularized tumors classified as grade I according to World Health Organization classification systems. About 3% of all intramedullary tumors are hemangioblastomas.1,2 Spinal cord hemangioblastomas are either sporadic3,4 or manifestations of von Hippel-Lindau (VHL) disease in 20% to 45% of patients.5,6 A 30-year-old male presented with sudden onset urinary incontinence. Magnetic resonance imaging showed contrast enhancing intramedullary tumor with adjacent cyst in T11, and syringomyelia extending to C1. Surgical resection followed rules that apply to resection of arteriovascular malformations: coagulation of arterial feeders precedes the coagulation of the draining vein, which is preserved until the end of surgery.2,4,5,7,8 First, posterior midline myelotomy was performed and the tumor cyst was drained in order to develop a dissection plane. Following this, we continuously separated dorsal nerve roots from the tumor nodule using microsurgical technique. The key step in tumor resection is devascularization of the tumor, achievable in 2 ways.2,7,9-13 The circumferential detachment of the normal pia from the tumor pia is crucial in developing a plane of dissection. The coagulation and division of arterial feeders while preserving the drainage vein further devascularizes the tumor. Once the tumor mural nodule was detached from the spinal cord, the drainage vein was coagulated last and the tumor was removed. The patient fully recovered from his incontinence and was neurologically intact. Screening for VHL disease was negative. Written consent was obtained directly from the patient. PMID- 29788140 TI - Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study. AB - Background: We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. Methods: We included 1297 subjects (mean age +/- standard error 48.0 +/- 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80 degrees C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. Results: After an average at-risk follow up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of >=30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04-1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15-1.55) for IRAE; HR 1.38 (1.06-1.79) for IURAE; HR 1.62 (1.22-2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. Conclusions: IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment. PMID- 29788141 TI - A Single Nucleotide Polymorphism in the Vitamin D Receptor Gene Is Associated With Decreased Levels of the Protein and a Penetrating Pattern in Crohn's Disease. AB - Background: Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR). The synonymous single nucleotide polymorphism (SNP) rs731236, located in the VDR gene, has been associated with a higher risk of Crohn's disease (CD). We analyzed differences in VDR expression levels among CD patients who were homozygous for allelic variants in this SNP and their relevance for disease course. Methods: DNA was extracted from blood samples of CD patients, and SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Fresh blood from patients was used to isolate peripheral blood mononuclear cells (PBMCs) or to determine the expression of adhesion molecules by flow cytometry. We analyzed the gene expression of VDR and several cytokines in PBMCs using real-time polymerase chain reaction and the protein levels of VDR, NFkappaB, and IkappaBalpha by immunoblot. In addition, we collected complete clinical data for a group of 103 patients, including age at diagnosis, disease location, and disease behavior to compare patient characteristics with respect to genotype. Results: We found that CD patients who were homozygous for the risk allele presented lower levels of VDR protein in PBMCs, and that this was associated with an upregulation of IL1beta mRNA and activation of lymphocytic adhesion molecules. These patients had a higher risk of developing a B3-penetrating phenotype and of needing to undergo surgery. Conclusion: Our data highlight the relevance of vitamin D/VDR signaling in modulating the subjacent inflammation that leads to CD-related complications. PMID- 29788142 TI - Molecular Characterization of the 2016 New World Screwworm (Diptera: Calliphoridae) Outbreak in the Florida Keys. AB - New World screwworm (NWS), Cochliomyia hominivorax (Coquerel 1858) (Diptera: Calliphoridae), is a myiasis-causing fly that can be a serious threat to the health of livestock, wildlife, and humans. Its progressive eradication from the southern United States, Mexico, and Central America from the 1950s to 2000s is an excellent example of successful pest management using sterile insect technique (SIT). In late 2016, autochthonous NWS were detected in the Florida Keys, representing this species' first invasion in the United States in >30 yr. Rapid use of quarantine and SIT was successful in eliminating the infestation by early 2017; however, the geographic source of this infestation remains unknown. Here, we use amplicon sequencing to generate mitochondrial and nuclear sequence data representing all confirmed cases of NWS from this infestation, and compare these sequences to preexisting data sets sampling the native distribution of NWS. We ask two questions regarding the FL Keys outbreak. First, is this infestation the result of a single invasion from one source, or multiple invasions from different sources? And second, what is the geographic origin of this invasion? We found virtually no sequence variation between specimens collected from the FL Keys outbreak, which is consistent with a single source of introduction. However, we also found very little geographic resolution in any of the data sets, which precludes identification of the source of this outbreak. Our lack of success in answering our second question speaks to the need for finer-scale genetic or genomic assessments of NWS population structure, which would facilitate source determination of potential future outbreaks. PMID- 29788143 TI - Pedunculated aortic thrombus propagating from the right coronary artery in a patient with IgA nephropathy. PMID- 29788144 TI - Prior Knowledge Guides Speech Segregation in Human Auditory Cortex. AB - Segregating concurrent sound streams is a computationally challenging task that requires integrating bottom-up acoustic cues (e.g. pitch) and top-down prior knowledge about sound streams. In a multi-talker environment, the brain can segregate different speakers in about 100 ms in auditory cortex. Here, we used magnetoencephalographic (MEG) recordings to investigate the temporal and spatial signature of how the brain utilizes prior knowledge to segregate 2 speech streams from the same speaker, which can hardly be separated based on bottom-up acoustic cues. In a primed condition, the participants know the target speech stream in advance while in an unprimed condition no such prior knowledge is available. Neural encoding of each speech stream is characterized by the MEG responses tracking the speech envelope. We demonstrate that an effect in bilateral superior temporal gyrus and superior temporal sulcus is much stronger in the primed condition than in the unprimed condition. Priming effects are observed at about 100 ms latency and last more than 600 ms. Interestingly, prior knowledge about the target stream facilitates speech segregation by mainly suppressing the neural tracking of the non-target speech stream. In sum, prior knowledge leads to reliable speech segregation in auditory cortex, even in the absence of reliable bottom-up speech segregation cue. PMID- 29788145 TI - Long-Term Outcome of Spinal Cord Stimulation in Failed Back Surgery Syndrome: 20 Years of Experience With 224 Consecutive Patients. AB - BACKGROUND: Failed back surgery syndrome (FBSS) is a challenging condition that lacks a curative treatment. In selected patients, spinal cord stimulation (SCS) has provided a satisfactory outcome. OBJECTIVE: To evaluate the long-term outcome of SCS in FBSS, as measured by (1) the explantation rate, (2) complications, and (3) patient satisfaction with the global perceived effect (GPE). METHODS: We studied 224 consecutive FBSS patients who underwent an SCS trial with surgically implanted leads at our hospital between January 1996 and December 2014. The patients' satisfaction with the GPE of treatment was measured through a postal questionnaire at the end of follow-up. RESULTS: Based on a 1-wk trial, permanent SCS was implanted in 175 (78%) patients. Out of these patients, 153 (87%) reported satisfactory outcomes after 2 mo. During the mean follow-up of 6 yr, 34 (19%) of SCS devices were permanently explanted due to inadequate pain relief, and 11 (6%) were explanted for other reasons. Electrode revision due to inadequate pain relief was done for 22 patients. In total, 26 complications were reported due to: 7 deep infections, 11 hardware malfunctions, 1 subcutaneous hematoma, 4 instances of discomfort due to the pulse generator, and 3 electrode migrations. One hundred thirty patients (74%) continued with SCS until the end of follow-up. Of them, 61 (47%) returned the questionnaire, and 42 (69%) reported substantially improved or better GPE. CONCLUSION: SCS can provide a good outcome in the treatment of FBSS. Patient selection could be further improved by developing novel predictive biomarkers. PMID- 29788147 TI - Will the Eu Data Protection Regulation 2016/679 Inhibit Critical Care Research? AB - There is an inherent tension between critical care research and data protection. Because of their condition it is not possible to ask for the patients' informed consent to be enrolled in observational research at the point of admission to the hospital. Often this is not possible at a later moment either. Yet informed consent is the baseline to be enrolled in research with personal data and exceptions must be allowed for by national legislation. This was the case under Directive 95/96/EC and will be the case under the General Data Protection Regulation (GDPR, Regulation 2016/679 EU) which will replace the Directive from 25 May 2018 onwards. Though being a Regulation and therefore directly applicable in the Member States, the long debate about the research exceptions in the GDPR left many aspects of observational research including the exception to the informed consent principle, mainly to the Member States. It may be assumed that most Member States will leave their present state of the law intact in this respect as that was part of the political compromise. We compared existing national privacy legislation from the perspective of critical care research and found great variation. Although this may not impede the collection of emergency and critical care research with data without prior informed consent in countries which are more responsive to such research, it might be a challenge to exchange such data from the national nodes in European wide research collaboration. We make a case that countries which are not responsive to such research should adapt their legislation in the interests of future critical care patients. PMID- 29788148 TI - The Role of Angiogenesis Inhibitors in Hypertension: Following "Ariadne's Thread". AB - Arterial hypertension (HT) is one of the most frequently recorded comorbidities among patients under antiangiogenic therapy. Inhibitors of vascular endothelial growth factor and vascular endothelial growth factor receptors are most commonly involved in new onset or exacerbation of pre-existing controlled HT. From the pathophysiology point of view, data support that reduced nitric oxide release and sodium and fluid retention, microvascular rarefaction, elevated vasoconstrictor levels, and globular injury might contribute to HT. The purpose of this review was to present recent evidence regarding the incidence of HT induced by antiangiogenic agents, to analyze the pathophysiological mechanisms, and to summarize current recommendations for the management of elevated blood pressure in this field. PMID- 29788146 TI - Leaf hydraulic vulnerability triggers the decline in stomatal and mesophyll conductance during drought in rice. AB - Understanding the physiological responses of crops to drought is important for ensuring sustained crop productivity under climate change, which is expected to exacerbate the frequency and intensity of periods of drought. Drought responses involve multiple traits, and the correlations between these traits are poorly understood. Using a variety of techniques, we estimated the changes in gas exchange, leaf hydraulic conductance, and leaf turgor in rice (Oryza sativa) in response to both short- and long-term soil drought. We performed a photosynthetic limitation analysis to quantify the contributions of each limiting factor to the resultant overall decrease in photosynthesis during drought. Biomass, leaf area, and leaf width significantly decreased during the 2-week drought treatment, but leaf mass per area and leaf vein density increased. Light-saturated photosynthetic rate declined dramatically during soil drought, mainly due to the decrease in stomatal conductance (gs) and mesophyll conductance (gm). Stomatal modeling suggested that the decline in leaf hydraulic conductance explained most of the decrease in stomatal closure during the drought treatment, and may also trigger the drought-related decrease of stomatal conductance and mesophyll conductance. The results of this study provide insight into the regulation of carbon assimilation under drought conditions. PMID- 29788149 TI - Randomized trials and propensity score analyses in transcatheter aortic valve replacement: how should we interpret the results? PMID- 29788150 TI - Spotlight on recently published ICVTS articles. PMID- 29788151 TI - Sporulation environment influences spore properties in Bacillus: evidence and insights on underlying molecular and physiological mechanisms. AB - Bacterial spores are resistant to physical and chemical insults, which makes them a major concern for public health and industry. Spores help bacteria to survive extreme environmental conditions that vegetative cells cannot tolerate. Spore resistance and dormancy are important properties for applications in medicine, veterinary health, food safety, crop protection and other domains. The resistance of bacterial spores results from a protective multilayered structure and from the unique composition of the spore core. The mechanisms of sporulation and germination, the first stage after breaking of dormancy, and organization of spore structure have been extensively studied in Bacillus species. This review aims to illustrate how far the structure, composition and properties of spores are shaped by the environmental conditions in which spores form. We look at the physiological and molecular mechanisms underpinning how sporulation media and environment deeply affect spore yield, spore properties like resistance to wet heat and physical and chemical agents, germination and further growth. For example, spore core water content decreases as sporulation temperature increases, and resistance to wet heat increases. Controlling the fate of Bacillus spores is pivotal to controlling bacterial risks and process efficiencies in, for example, the food industry, and better control hinges on better understanding how sporulation conditions influence spore properties. PMID- 29788152 TI - Early Arthritis Is Associated With Failure of Immunosuppressive Drugs and Severe Pediatric Crohn's Disease Evolution. AB - Background: Crohn's disease (CD) is a chronic relapsing inflammatory disease. To optimize therapeutic decision making, it is essential to identify parameters that allow early prediction of a severe disease course. The aim of this study was to assess the link between arthritis and medium-term therapeutic failure in pediatric CD. Methods: We conducted a population-based cohort study with prospectively collected electronic data. To be included, patients must be younger than 17 years and have a confirmed CD diagnosed between 2005 and 2014. The primary outcome was the percentage of patients with at least 1 therapeutic failure of immunosuppressive drugs during the 2 years after the CD diagnosis, with a propensity score analysis. Results: We included 272 patients with CD. The median age was 12.1 years (interquartile [10.1-14.2]). Sixty-five patients (23.9%) developed arthritis, which predominantly occurred during the first year after CD diagnosis. We found a highly significant association between arthritis and therapeutic failure of immunosuppressive drugs after 2 years (OR = 6.9; 95% confidence interval [CI], 2.7-18.0; P < 0.0001; propensity score matching analysis). Arthritis was also significantly associated with introduction of biotherapy due to luminal disease 2 years after diagnosis (OR = 3.2, 95% CI, 1.8 6.0; P = 0.0001). Similar results were obtained after 4 years, and arthritis was significantly associated with a higher number of hospitalizations for luminal flare-up or complications after 4 years (OR = 2.2; 95% CI, 1.2-3.9; P = 0.007). Conclusions: Arthritis was strongly associated with medium-term therapeutic failure of pediatric CD. Occurrence of arthritis early in the disease may justify closer follow-up visits or specific therapeutic management. PMID- 29788153 TI - Aggregate analysis of sentinel events as a strategic tool in safety management can contribute to the improvement of healthcare safety. AB - Objective: To examine if clustering of root causes of sentinel events (SEs) can contribute to organisational improvement of healthcare and patient safety by providing insight into organisational risk factors, patterns and trends. Design: Retrospective, cross-sectional review of SEs from a hospital database reported to the Board of directors in 2016. Setting: A regional teaching hospital in the Netherlands. Intervention(s): Clustering of characteristics and variables of SEs to establish vulnerabilities and patterns of failure factors of the organisation. Main Outcome Measure(s): Characteristics and contributory causes of failure of SEs identified via root cause analysis (RCA). Outcomes reported using descriptive statistics. Results: A total of 21 events were included involving 21 patients. Mean age was 56.7 years (SD 24.4), 71.4% were above 50 years of age. In 81.8%, the care was multi-disciplinary and in 76.2% the event resulted in permanent harm or injury. Of the 132 identified contributory root causes, most were related to human factors (53.8%) and organisational factors (40.2%). Technical and patient related factors were identified in 3.0%. Organisational improvement strategies focused on the care of elderly patients, patients subjected to multi-disciplinary care and on improving knowledge, protocols and coordination of care. Conclusion: Clustering variables of SEs and contributory factors of failure through RCA helps to delineate a hospital-specific profile by providing a detailed insight into risk factors, patterns and trends in an organisation and to determine the best strategies for improvement by drawing lessons across events. PMID- 29788154 TI - Macrovascular Decompression of Facial Nerve With Anteromedial Transposition of a Dolichoectatic Vertebral Artery: 3-Dimensional Operative Video. AB - Most cranial nerve compression syndromes (ie, trigeminal neuralgia and hemifacial spasm) are caused by small arteries impinging on a nerve and are relieved by microvascular decompression. Rarely, cranial nerve compression syndromes can be caused by large artery impingement and can be relieved by macrovascular decompression. When present, this compression often occurs in association with degenerative atherosclerosis in the vertebral arteries (VA) and basilar artery. Conservative treatment is recommended for mild forms, but surgical transposition of the VA away from the root entry zone (REZ) can be considered. This video demonstrates macrovascular decompression of a dolichoectatic VA in a 74-yr-old female with refractory left hemifacial spasm. After obtaining IRB approval, patient consent was sought for the procedure. With the patient in three-quarter prone position, a far-lateral craniotomy was performed. The dentate ligament was cut to free the VA, and the suprahypoglossal portion of the vagoaccessory triangle was widened. VA compressed the REZ of the facial nerve, but was mobilized anteromedially off the REZ. A muslin sling was wrapped around the VA and its tail brought down to the clival dura, which was punctured with a 19-gauge needle and enlarged with a dissector. The sling was pulled anteromedially to this puncture site and secured to the dura with an aneurysm clip, relieving the REZ of all compression. The patient tolerated the procedure with mild, transient hoarseness and her hemifacial spasm resolved completely. This case demonstrates the macrovascular decompression technique with anteromedial transposition of the vertebrobasilar artery, which can also be used for trigeminal neuralgia. PMID- 29788156 TI - Systemic inflammation markers after simplification to atazanavir/ritonavir plus lamivudine in virologically suppressed HIV-1-infected patients: ATLAS-M substudy. AB - Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, 0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation. PMID- 29788157 TI - Weight loss in achalasia is determined by its phenotype. AB - Patients with achalasia present with dysphagia, regurgitation, and varying degrees of weight loss. However, despite it being a disorder of the lower esophageal sphincter with functional obstruction in all patients, it is unclear why certain patients lose significantly more weight compared to others. The aims of this study are to assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population. Patients with diagnosis of achalasia referred to our center between 2009 and 2016 were evaluated. Demographic and physiologic tests between those with and without weight loss were compared. The cohort of patients with initial self-reported weight loss were studied to determine change in weight after intervention (pneumatic dilation or myotomy). The Kruskal-Wallis test was used for comparison of continuous variables between groups and Pearson's chi2 test was used for comparison of categorical variables between groups. 138 patients with achalasia were evaluated. 35 patients were excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients with achalasia [51% male, median age: 56 years]. Weight loss was reported in 51/100 (51%) patients. BMI was lower in patients who reported weight loss (25 vs. 31, P < 0.001) with a median weight loss of 28 lbs (14-40 lbs). There were no significant differences in age at diagnosis, gender, or symptom presentation (dysphagia, regurgitation, or chest pain) between the groups. However, more patients with type II achalasia (63%) reported weight loss as compared to other sub-types (P = 0.013). 73% of type III achalasia denied having weight loss. Patients who denied weight loss had symptoms for longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Postintervention 42% of patients reported no weight regain despite appropriate therapy for achalasia with median follow-up of 22 months (range: 6-90 months). Type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade in achalasia phenotypes deserves special attention. PMID- 29788155 TI - Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. AB - Background: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed. Patients and methods: In this phase I open-label study, in the dose escalation stage, patients were enrolled in a GDC-0575 monotherapy Arm (1) or GDC 0575 combination with gemcitabine Arm (2) to determine the maximum tolerated dose. Patients in arm 2 received either i.v. gemcitabine 1000 mg/m2 (arm 2a) or 500 mg/m2 (arm 2b), followed by GDC-0575 (45 or 80 mg, respectively, as RP2D). Stage II enrolled disease-specific cohorts. Results: Of 102 patients treated, 70% were female, the median age was 59 years (range 27-85), and 47% were Eastern Cooperative Oncology Group PS 0. The most common tumor type was breast (37%). The most frequent adverse events (all grades) related to GDC-0575 and/or gemcitabine were neutropenia (68%), anemia (48%), nausea (43%), fatigue (42%), and thrombocytopenia (35%). Maximum concentrations of GDC-0575 were achieved within 2 hours of dosing, and half-life was ~23 hours. No pharmacokinetic drug-drug interaction was observed between GDC-0575 and gemcitabine. Among patients treated with GDC-0575 and gemcitabine, there were four confirmed partial responses, three occurring in patients with tumors harboring TP53 mutation. Pharmacodynamic data were consistent with GDC-0575 inhibition of gemcitabine-induced expression of pCDK1/2. Conclusion: GDC-0575 can be safely administered as a monotherapy and in combination with gemcitabine; however, overall tolerability with gemcitabine was modest. Hematological toxicities were frequent but manageable. Preliminary antitumor activity was observed but limited to a small number of patients with a variety of refractory solid tumors treated with GDC-0575 and gemcitabine. Clinical trial number: NCT01564251. PMID- 29788159 TI - Perspectives on hypertension treatment in older persons. PMID- 29788160 TI - Mind the eye-squirter! An Anthia sexmaculata sexmaculata-related necrotic burn. AB - We report the case of an Anthia sexmaculata sexmaculata-associated necrotic burn in a French expatriate in Mauritania. Anthia spp.-related injury is a common though underreported health issue in the Sahelo-Saharan area. Deployed soldiers and travellers should be aware of these beetles when adventuring in this region. PMID- 29788158 TI - Cell wall-bound silicon optimizes ammonium uptake and metabolism in rice cells. AB - Background and Aims: Turgor-driven plant cell growth depends on cell wall structure and mechanics. Strengthening of cell walls on the basis of an association and interaction with silicon (Si) could lead to improved nutrient uptake and optimized growth and metabolism in rice (Oryza sativa). However, the structural basis and physiological mechanisms of nutrient uptake and metabolism optimization under Si assistance remain obscure. Methods: Single-cell level biophysical measurements, including in situ non-invasive micro-testing (NMT) of NH4+ ion fluxes, atomic force microscopy (AFM) of cell walls, and electrolyte leakage and membrane potential, as well as whole-cell proteomics using isobaric tags for relative and absolute quantification (iTRAQ), were performed. Key Results: The altered cell wall structure increases the uptake rate of the main nutrient NH4+ in Si-accumulating cells, whereas the rate is only half in Si deprived counterparts. Conclusions: Rigid cell walls enhanced by a wall-bound form of Si as the structural basis stabilize cell membranes. This, in turn, optimizes nutrient uptake of the cells in the same growth phase without any requirement for up-regulation of transmembrane ammonium transporters. Optimization of cellular nutrient acquisition strategies can substantially improve performance in terms of growth, metabolism and stress resistance. PMID- 29788161 TI - New reagents for poultry research: preparation, purification, and in vitro evaluation of non-PEGylated and mono-PEGylated chicken prolactin. AB - Recombinant chicken prolactin (chPRL), expressed in Escherichia coli and purified as a monomer, was successfully PEGylated and purified to homogeneity as a mono PEGylated protein (PEG-chPRL). Its biological activity was estimated by its ability to interact with human prolactin receptor extracellular domain (hPRLR ECD) and stimulate PRLR-mediated proliferation in Nb2-11C cells. PEG-chPRL activity in a cell bioassay was 10-fold lower than that of non-PEGylated chPRL, but only 2-fold lower in a binding assay to hPRLR-ECD. The CD spectra of non PEGylated and PEGylated chPRL were almost identical and similar to that of hPRL, indicating proper refolding. Although the PEGylation of chPRL resulted in lower activity in vitro, PEG-chPRL was absorbed more slowly than chPRL, remained in the circulation 16 h longer. Furthermore the effects of PEG-chPRL injections in chickens on subsequent corticosteroid levels in blood were significantly profound compared to chPRL. These favorable PEGylation-induced pharmacokinetic alterations should improve efficacy of PEG-chPRL in in vivo experiments, as dosing frequency can be reduced due to its prolonged persistence in the circulation, and thus reduce the frequency of dosing. Furthermore, hydrophobic interaction chromatography was successfully adopted to isolate PEG-chPRL as a better alternative for separation of PEGylated PRL, and is likely to be successfully applicable to other proteins. PMID- 29788162 TI - Symposium: avian embryo nutrition and incubation. AB - The embryonic period represents approximately 33 percent of the total productive life of modern broilers and is very important for attaining quality broiler performance at marketing. In this symposium, recent developments in pre-hatch broiler development were discussed with special focus on maternal nutrition, in ovo nutrition, and the regulation and monitoring of the incubational environment. The symposium was concluded with discussion about the implementation of future innovations in incubation technology. PMID- 29788163 TI - Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis. PMID- 29788164 TI - What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis. AB - Background: Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Methods: Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. Results: We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Conclusions: Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta analysis based on individual participant data is in development. PMID- 29788165 TI - Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis. AB - Background: Prostate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality. Materials and methods: Published articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case-control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years. Results: In random effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94-1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80-1.06) and 0.95 (95% CI = 0.85-1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71-0.98, n studies = 13), although that finding became statistically non significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37 0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60-0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55-0.85). Conclusions: Whether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality. PMID- 29788167 TI - Treatment effects measured by restricted mean survival time in trials of immune checkpoint inhibitors for cancer. AB - Background: The hazard ratio (HR) is used routinely to quantify the treatment effect for time-to-event end points in oncology trials, but its use requires that there be proportional hazards in the treatment arms. Non-proportional hazards are observed frequently in cancer immunotherapy trials due to the long-term survival and delayed clinical effect. Although values of HR are quoted in such trials, they are not valid measures of outcome. Methods: Reports of parallel group randomized controlled trials (RCTs) evaluating immune checkpoint inhibitors with overall survival data were eligible. For each trial, the ratio of restricted mean survival time (RMST) between the arms was based on reconstructed individual patient data for overall survival. Results: Twenty-five RCTs totaling 12 870 patients were included in this study. Overall survival was used as primary or coprimary end point in 18 trials (72%). In all trials, there was agreement between the ratio of RMST or RMTL and the reported HR about the direction of treatment effect. Estimates of HR provided larger estimates of treatment effect than the ratio of RMST or RMTL in all these trials. The estimated HR and RMST based measures were in agreement regarding the statistical significance of the effect in all but two trials. Conclusions: Ratio of RMST is a complementary technique that provides alternative method of summarizing treatment effects. Proportional hazards of the treatment effect should not be assumed in RCTs evaluating immune checkpoint inhibitors, and RMST analysis should be reported in such trials. PMID- 29788166 TI - Combined pathologic-genomic algorithm for early-stage breast cancer improves cost effective use of the 21-gene recurrence score assay. AB - Background: The 21-gene recurrence score (RS) (Oncotype DX(r); Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk. PMID- 29788168 TI - Nivolumab combined with ruxolitinib: antagonism or synergy? PMID- 29788169 TI - HPV status, like politics, is local-evaluating p16 staining and a new staging system in a Dutch cohort of oropharynx cancer. PMID- 29788171 TI - It is time to rethink weight loss in cancer. PMID- 29788172 TI - Temporary protection: its impact on healthcare for Syrian refugees in Turkey. PMID- 29788170 TI - Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials. AB - Background: Driven by reduced nutritional intakes and metabolic alterations, malnutrition in cancer patients adversely affects quality of life, treatment tolerance and survival. We examined evidence for oral nutritional interventions during chemo(radio)therapy. Design: We carried out a systematic review of randomized controlled trials (RCT) with either dietary counseling (DC), high energy oral nutritional supplements (ONS) aiming at improving intakes or ONS enriched with protein and n-3 polyunsaturated fatty acids (PUFA) additionally aiming for modulation of cancer-related metabolic alterations. Meta-analyses were carried out on body weight (BW) response to nutritional interventions, with subgroup analyses for DC and/or high-energy ONS or high-protein n-3 PUFA-enriched ONS. Results: Eleven studies were identified. Meta-analysis showed overall benefit of interventions on BW during chemo(radio)therapy (+1.31 kg, 95% CI 0.24 2.38, P = 0.02, heterogeneity Q = 21.1, P = 0.007). Subgroup analysis showed no effect of DC and/or high-energy ONS (+0.80 kg, 95% CI -1.14 to 2.74, P = 0.32; Q = 10.5, P = 0.03), possibly due to limited compliance and intakes falling short of intake goals. A significant effect was observed for high-protein n-3 PUFA enriched intervention compared with isocaloric controls (+1.89 kg, 95% CI 0.51 3.27, P = 0.02; Q = 3.1 P = 0.37). High-protein, n-3 PUFA-enriched ONS studies showed attenuation of lean body mass loss (N = 2 studies) and improvement of some quality of life domains (N = 3 studies). Overall, studies were limited in number, heterogeneous, and inadequately powered to show effects on treatment toxicity or survival. Conclusion: This systematic review suggests an overall positive effect of nutritional interventions during chemo(radio)therapy on BW. Subgroup analyses showed effects were driven by high-protein n-3 PUFA-enriched ONS, suggesting the benefit of targeting metabolic alterations. DC and/or high-energy ONS were less effective, likely due to cumulative caloric deficits despite interventions. We highlight the need and provide recommendations for well-designed RCT to determine the effect of nutritional interventions on clinical outcomes, with specific focus on reaching nutritional goals and providing the right nutrients, as part of an integral supportive care approach. PMID- 29788173 TI - Overexpression of Golgi Phosphoprotein 2 Is Associated With Poor Prognosis in Oral Squamous Cell Carcinoma. AB - Objectives: The aims of this study were to investigate the relationship between Golgi phosphoprotein 2 (GOLPH2) and oral squamous cell carcinoma (OSCC) and explore the clinical significance of GOLPH2 in OSCC. Methods: Tissue microarrays from human OSCC samples were stained for GOLPH2 expression and clinicopathologic features. Kaplan-Meier analysis was used to compare the survival of patients with high GOLPH2 expression and patients with low GOLPH2 expression. Results: We found GOLPH2 is highly expressed in OSCC tissue, and the GOLPH2 expression in metastatic lymph nodes is higher than in tumor tissue. Our data indicate that patients with higher GOLPH2 expression have poor overall survival compared with those with lower GOLPH2 expression. This study demonstrated that GOLPH2 was associated with CD44, SOX2, Slug, B7-H3, B7-H4, TIM3, and VISTA. Conclusions: These findings suggest GOLPH2 is a potential marker for estimating the patient's prognosis and may be a target for molecular-targeted therapy against OSCC. PMID- 29788175 TI - Prevalence of XXY karyotypes in human blastocysts: multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF. AB - STUDY QUESTION: Which is the prevalence of a 47,XXY karyotype in human blastocysts biopsied during preimplantation genetic testing for aneuploidies (PGT A) cycles? SUMMARY ANSWER: The prevalence of a 47,XXY karyotype amongst male blastocysts without autosomal aneuploides is ~1%. WHAT IS KNOWN ALREADY: The prevalence of Klinefelter syndrome is estimated as 0.1-0.2% in male newborns. However, the KS phenotype is extremely variable and there are men with a 47,XXY karyotype and less evident signs, who may go undetected. No risk factor for the 47,XXY karyotype in products of conception has been yet clearly defined, and no data are available regarding the prevalence of this karyotype among human preimplantation embryos. STUDY DESIGN, SIZE, DURATION: This multicentre cohort study involved 7549 blastocysts obtained during 2826 PGT-A cycles performed between April 2013 and September 2017 at six IVF clinics in Italy. PARTICIPANTS/MATERIALS, SETTING, METHODS: During 2826 PGT-A cycles, 7549 blastocysts underwent trophectoderm biopsy and quantitative-PCR-based comprehensive chromosomal testing to predict the karyotype of the corresponding embryos. The results were also presented according to ranges of maternal and paternal age at oocyte retrieval as well as sperm factor and blastocyst quality. Univariate and multivariate logistic regression analyses were conducted to investigate the correlation of possible confounding factors with the prevalence of 47,XXY karyotype. MAIN RESULTS, THE ROLE OF CHANCE: Overall, 62 blastocysts were 47,XXY or had an XXY karyotype associated with autosomal aneuploidies. After exclusion of the latter, the prevalence of a 47,XXY karyotype among male blastocysts without autosomal aneuploidies was 0.9% (n = 17/1794). A significant correlation was only found for maternal age and blastocyst quality (OR: 1.20, 95% CI: 1.01-1.42; P = 0.04 and OR: 1.6, 95% CI: 1.13-2.45; P = 0.01). LIMITATIONS, REASONS FOR CAUTION: These retrospective data have been produced based on a population of infertile couples undergoing IVF and PGT-A, and the women were mainly of advanced maternal age. Moreover, the qPCR technique is validated only to detect full-chromosome uniform aneuploidies in trophectoderm biopsies. WIDER IMPLICATIONS OF THE FINDINGS: The 0.9% prevalence of the 47,XXY karyotype among male blastocysts, when compared with the 0.1-0.2% prevalence reported in the prenatal and postnatal periods, suggests four possible scenarios that require further investigations: (i) the latter prevalence is underestimated; (ii) 47,XXY blastocysts result in a lower implantation rate than euploid embryos (estimated to be ~50%); (iii) 47,XXY blastocysts result in a higher early miscarriage rate than euploid embryos (estimated to be ~10%); or (iv) infertile patients of advanced maternal age and referred to IVF/PGT-A produce a higher rate of 47,XXY blastocysts. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A. PMID- 29788174 TI - Aspirin Abrogates Impairment of Mammary Gland Differentiation induced by Early in Life Second-hand Smoke in Mice. AB - Epidemiological studies show that there is limited evidence that tobacco smoking causes breast cancer in humans. In rodents, many tobacco smoke chemicals cause mammary gland tumors. This study evaluated the mammary gland differentiation in mice exposed to environmental cigarette smoke (ECS), using 3R4F Kentucky reference cigarettes, starting after birth and continuing daily for 10 weeks (total particulate exposure 95 mg/m3; CO 610 ppm). We also analyzed the effects of oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin (1600mg/kg) or naproxen (320mg/kg), on mammary gland differentiation, either in unexposed or ECS-exposed mice. The ECS exposure caused delay of mammary glands development. We speculate that this delay may result from aryl hydrocarbon receptor (AHR) signaling activation, which has an antiestrogenic effect and crosstalk to the estrogen metabolism pathway. Similarly, naproxen impaired gland differentiation in unexposed and ECS-exposed mice, while aspirin hindered its development only in unexposed mice. The lack of differentiation induced by the NSAIDs could be explained by their antiestrogenic effect through inhibition of aldo-keto reductases. In ECS-exposed animals, aspirin induced intense lobular formation, which could indicate that aspirin is counteracting the AHR signaling induced by ECS. Based on the differentiation induced by aspirin in ECS-exposed animals, we postulate that these mice would be less susceptible to mammary carcinogenesis. Our results suggest that exposure to smoke at an early age impairs the development of the mammary gland, thus resulting in a longer period of susceptibility and increased risk of breast cancer. However, addition of aspirin can abrogate this effect. PMID- 29788177 TI - GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models. AB - Due to the involvement of G protein-coupled receptors (GPCRs) in most of the physiological and pathological processes in humans they have been attracting a lot of attention from pharmaceutical industry as well as from scientific community. Therefore, the need for new, high quality structures of GPCRs is enormous. The updated homology modeling service GPCRM (http://gpcrm.biomodellab.eu/) meets those expectations by greatly reducing the execution time of submissions (from days to hours/minutes) with nearly the same average quality of obtained models. Additionally, due to three different scoring functions (Rosetta, Rosetta-MP, BCL::Score) it is possible to select accurate models for the required purposes: the structure of the binding site, the transmembrane domain or the overall shape of the receptor. Currently, no other web service for GPCR modeling provides this possibility. GPCRM is continually upgraded in a semi-automatic way and the number of template structures has increased from 20 in 2013 to over 90 including structures the same receptor with different ligands which can influence the structure not only in the on/off manner. Two types of protein viewers can be used for visual inspection of obtained models. The extended sortable tables with available templates provide links to external databases and display ligand-receptor interactions in visual form. PMID- 29788179 TI - Normative Data for the BTrackS Balance Test of Postural Sway: Results from 16,357 Community-Dwelling Individuals Who Were 5 to 100 Years Old. AB - Background: Postural sway is routinely assessed because increased postural sway is associated with poorer performance of activities of daily living, higher rates of residential care, and increased risk of falling. Force plate technology is one of the most sensitive and objective means of assessing postural sway in the clinic. Objective: The aim of this study was to provide the first set of normative data for the BTrackS Balance Test (BBT) of postural sway. Design: The design was descriptive and population based. Methods: BBT results from 16,357 community-dwelling individuals who were 5 to 100 years old were accumulated and assessed for effects of age, sex, height, and weight. Percentile rankings were calculated for significant groupings. Results: BBT results were dependent on age and sex but not height or weight. Therefore, percentile rankings were determined for male and female individuals in each age category, with no consideration of participant height or weight. Limitations: Data were collected by third-party practitioners with various backgrounds in more than 50 locations across the United States and Canada. There was an imbalance in the sample sizes for age and sex groupings. Conclusions: The findings of this study represent the largest normative dataset ever published for postural sway results. Normative data on the BBT can assist in determining abnormalities in postural sway, which have been linked to negative clinical outcomes. PMID- 29788176 TI - Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii. AB - Toxoplasma gondii virulence depends on the expression of factors packed into specific organelles such as rhoptry and microneme. Although virulence factor expression is tightly regulated, the molecular mechanisms controlling their regulation remain poorly understood. ApiAP2 are a family of conserved transcription factors (TFs) that play an important role in regulating gene expression in apicomplexan parasites. TgAP2XI-5 is able to bind to transcriptionally active promoters of genes expressed during the S/M phase of the cell cycle, such as virulence genes (rhoptries and micronemes genes). We identified proteins interacting with TgAP2XI-5 including a cell cycle-regulated ApiAP2 TF, TgAP2X-5. Using an inducible knock-down strategy and RNA-seq, we demonstrated that the level of expression of number of virulence factors transcripts is affected by the disruption of TgAP2X-5 expression. While TgAP2X-5 disruption has mild effect on parasite invasion, it leads to the strain avirulence in mice. To better understand the molecular mechanisms at stake, we investigated the binding of TgAP2XI-5 at promoters in the TgAP2X-5 mutant strain in a genome-wide assay. We show that disruption of TgAP2X-5 expression leads to defects in TgAP2XI-5 binding to multiple rhoptry gene promoters. Taken together, these data suggest a cooperative contribution of two ApiAP2 TF in the regulation of virulence genes in T. gondii. PMID- 29788178 TI - Evaluation of the Entomopathogenic Fungi Metarhizium anisopliae, Beauveria bassiana and Isaria sp. for the Management of Aphis craccivora (Hemiptera: Aphididdae). AB - Cowpea, Vigna unguiculata ((L.) Walp; Fabales: Fabaceae), is an important indigenous vegetable and grain legume in the tropics where it represents a major diet component. Cowpea aphid, Aphis craccivora (Koch; Hemiptera: Aphididdae) is a major pest causing up to 100% yield losses. Aiming at establishing alternative approach to synthetic insecticides, we evaluated the pathogenicity of 23 fungal isolates including Metarhizium anisopliae ((Metschn.) Sorokin; Hypocreales: Clavicipitaceae), Beauveria bassiana ((Bals.) Vuill.; Hypocreales: Cordycipitaceae), and Isaria sp. (Hypocreales: Cordycipitaceae) against adult A. craccivora in the laboratory. Adult apterous aphids were sprayed with conidial suspensions titred at 1 * 108 conidia ml-1 for pathogenicity tests while 1 * 104, 1 * 105, 1 * 106, 1 * 107 and 1 * 108 conidia ml-1 were used in dose response bioassays. All the fungal isolates were found pathogenic to A. craccivora, causing mortality of between 34.5 and 90%. The lethal 50% mortality time (LT50) values varied between 3.3 and 6.3 d, with the best isolates being ICIPE 62, ICIPE 41 and ICIPE 644. The lethal concentration mortality (LC50) values were 2.3 * 106, 1.3 * 108 and 1.3 * 109 for ICIPE 62, ICIPE 41, and ICIPE 644, respectively. M. anisopliae isolate ICIPE 62 produced more conidia on aphid cadavers (4.5 * 107) than ICIPE 41 (2.7 * 107) and ICIPE 644 (2.1 * 107) 6 d post-treatment. Relative potency comparison showed that ICIPE 62 was more potent than the other two isolates. In the screenhouse, conidia of ICIPE 62 significantly reduced A. craccivora population compared to control but there was no significant difference between emulsifiable and aqueous formulations. Small-holder leafy vegetable producers could gain more profits using fungal-based biopesticides in Aphid-IPM strategies, leading to reduction of pre-harvest intervals after their application compared to synthetic insecticides. PMID- 29788180 TI - Rotavirus Vaccination Is Associated With Reduced Seizure Hospitalization Risk Among Commercially Insured US Children. AB - Rotavirus commonly causes diarrhea but can also cause seizures. Analysis of insurance claims for 1773295 US children with 2950 recorded seizures found that, compared to rotavirus-unvaccinated children, seizure hospitalization risk was reduced by 24% (95% confidence interval [CI], 13%-33%) and 14% (95% CI, 0%-26%) among fully and partially rotavirus-vaccinated children, respectively. PMID- 29788181 TI - Identification of Aggregation-Sex Pheromone of the Korean Monochamus alternatus (Coleoptera: Cerambycidae) Population, the Main Vector of Pine Wood Nematode. AB - We confirmed an aggregation-sex pheromone of the Korean Monochamus alternatus Hope (Coleoptera: Cerambycidae) population, which primarily transmitted the pine wood nematode in Korea. Only the M. alternatus male emitted monochamol which has been previously reported in the Chinese M. alternatus population. In field attraction testing, the monochamol+alpha-pinene+ethanol combination attracted more M. alternatus adult beetles than traps containing only monochamol, ethanol, or alpha-pinene. The bark beetle aggregation pheromone compounds of ipsenol, ipsdienol, and ipsenol+ipsdienol, did not show synergistic effects with the monochamol+alpha-pinene+ethanol combination. No synergistic effects were observed when each host volatile compound of 3-carene, beta-caryophyllene, limonene, myrcene, and beta-pinene was added to traps containing monochamol+alpha pinene+ethanol. The ratio of female beetles was much higher in traps containing the monochamol+alpha-pinene+ethanol combination than that of the natural population. Our results indicated that pheromone and synergists could be useful for managing the M. alternatus population. PMID- 29788183 TI - Membrane Rafts Regulate Sperm Acrosome Reaction via cAMP-dependent Pathway in Chickens (Gallus gallus domesticus). AB - Both transcriptionally and translationally inactive sperm need preassembled pathways into specific cellular compartments to function. Although initiation of the acrosome reaction (AR) involves several signaling pathways including protein kinase A (PKA) activation, how these are regulated remains poorly understood in avian sperm. Membrane rafts are specific membrane regions enriched in sterols and functional proteins and play important roles in diverse cellular processes, including signal transduction. Our recent studies on chicken sperm demonstrated that membrane rafts exist and play a role in multistage fertilization. These, combined with the functional importance of membrane rafts in mammalian sperm AR, prompted us to investigate the roles of membrane rafts in signaling pathways leading to AR in chicken sperm. Using 2-hydroxypropyl-beta-cyclodextrin (2-OHCD), we found that the disruption of membrane rafts inhibits PKA activity and AR without affecting protein tyrosine phosphorylation; however, these inhibitions were abolished in the presence of a cyclic 3',5'-monophosphate (cAMP) analogue. In addition, biochemical experiments showed a decrease in cAMP content in 2-OHCD treated sperm, suggesting the involvement of soluble adenylyl cyclase (sAC) and transmembrane adenylyl cyclase (tmAC). Pharmacological experiments, combined with transcriptome analysis, showed that sAC and tmAC are present and involved in AR induction in chicken sperm. Furthermore, stimulation of both isoforms reversed the inhibition of PKA activity and AR in 2-OHCD-treated sperm. In conclusion, our results demonstrated that membrane rafts play an important role in AR induction by regulating the cAMP-dependent pathway and that they provide a mechanistic insight into membrane regulation of AR and sperm function in birds. PMID- 29788182 TI - GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide. AB - Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest. PMID- 29788184 TI - Adverse effect of the financial crisis in Greece on perinatal factors. AB - Background: Starting in 2008 recession affected many European countries and especially Greece. Previous studies have reported increases in low birth weight, preterm birth and stillbirth rates in Greece during early crisis. In our study we used data on births from 1980 to 2014 that allowed us to distinguish recent changes, which could possibly be attributed to the financial crisis, from long term trends, and controlled for maternal age and country of origin as potential confounders. Our study covered a longer period (up to 2014) than what has been studied before and looked separately at the effect of early and established crisis. Methods: We used national vital statistics data from 1980 to 2014. We performed age standardization and calculated age standardized rates and standardized rate ratios (SRRs) for perinatal factors for three time periods (pre crisis, early crisis and established crisis) for Greek and non-Greek women. Results: We found an increase in low birth weight deliveries independent of maternal age and origin and an increased stillbirth rate in Greek women younger than 25 in early (RR = 1.42 95%CI: 1.12-1.80) and established crisis periods (RR = 1.36 95%CI: 1.07-1.72) compared with pre-crisis. Non-Greek women have also been affected, with their advantage regarding birth outcomes becoming less profound in the established crisis period (low birth weight: established crisis SRR = 0.84 95%CI: 0.82-0.87, pre-crisis SRR = 0.79 95% CI: 0.76- 0.81). Conclusions: The financial crisis has possibly adversely affected perinatal factors in Greece. Our results highlight the need of appropriate public health interventions and family support policies, especially for younger people, unemployed and immigrants. PMID- 29788185 TI - Cyclophosphamide-Induced Disruptions to Appetitive Qualities and Detection Thresholds of NaCl: Comparison of Single-Dose and Dose Fractionation Effects. AB - Chemotherapy is one of the most common treatments for cancer; however, a side effect is often altered taste. This study examined how cyclophosphamide, a chemotherapy drug, affects salt taste in mice. On the basis of previous findings, it was predicted that cyclophosphamide-induced disruptions in salt taste would be observed near days 2-4, 8-12, and 22-24 posttreatment, and that multiple, smaller doses would cause more severe disruptions to taste. To test these predictions, two experiments were performed, one using brief access testing to measure appetitive qualities, and another using operant conditioning to measure detection thresholds. After a single 100 mg/kg cyclophosphamide injection, peak alterations in brief access lick rates were seen near days 5-8 and 15 posttreatment, whereas peak alterations in detection thresholds were seen days 6, 14, and 20 posttreatment. After five 20 mg/kg injections of cyclophosphamide, brief access lick rates revealed disruptions only on postinjection day 8 whereas thresholds appeared to cycle, gradually increased to and decreased from peak elevations on posttreatment days 4, 10, 15, 20, and 23. Although salt taste functions were disrupted by cyclophosphamide, the patterns of these disruptions were less severe and shorter than expected from cell morphology studies, suggesting a functional adjustment to maintain behavioral accuracy. Fractionation of cyclophosphamide dosing had minimum effect on brief access responses but caused longer, cyclic like disruptions of detection thresholds compared to single-dose administration. PMID- 29788187 TI - Distracted Driving and Risk of Crash or Near-crash Involvement among Older Drivers using Naturalistic Driving Data with a Case-crossover Study Design. AB - Background: The purpose of this study was to examine the association between secondary task involvement and risk of crash and near-crash involvement among older drivers using naturalistic driving data. Methods: Data from drivers aged >=70 years in the Strategic Highway Research Program (SHRP2) Naturalistic Driving Study database was utilized. The personal vehicle of study participants was equipped with four video cameras enabling recording of the driver and the road environment. Secondary task involvement during a crash or near-crash event was compared to periods of non-crash involvement in a case-crossover study design. Conditional logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI). Results: Overall, engaging in any secondary task was not associated with crash (OR=0.94, 95% CI 0.68-1.29) or near-crash (OR=1.08, 95% CI 0.79-1.50) risk. The risk of a major crash event with cell phone use was 3.79 times higher than the risk with no cell phone use (95% CI 1.00-14.37). Other glances into the interior of the vehicle were associated with an increased risk of near-crash involvement (OR=2.55, 95% CI 1.24-5.26). Other distractions external to the vehicle were associated with a decreased risk of crash involvement (OR=0.53, 95% CI 0.30-0.94). Interacting with a passenger and talking/singing were not associated with crash or near-crash risk. Conclusions: Older drivers should avoid any cell phone use and minimize non-driving related eye glances towards the interior of the vehicle while driving. Certain types of events external to the vehicle are associated with a reduced crash risk among older drivers. PMID- 29788188 TI - Importance of Fenestration Size for Definitive Treatment of a Quadrigeminal Arachnoid Cyst: Endoscopic Inspection of the Cyst and Surrounding Anatomy: 2 Dimensional Operative Video. AB - Arachnoid cysts are fluid-filled sacs, located between the brain or spinal cord and the arachnoid membrane. Their prevalence in children is between 1% and 3%. Quadrigeminal arachnoid cysts represent 1% to 10% of them and are often associated with hydrocephalus, mostly by an obstructive mechanism, explained by compression of the tectum of the midbrain. When an indication for treatment is retained, 3 surgical options are available: microsurgical excision/fenestration, endoscopic fenestration, and shunt placement. Endoscopic treatment is considered the best compromise of definitive treatment with least surgical morbidity, especially because quadrigeminal cysts are located close to the midline, in intimate relationships with basal cisterns and ventricles. We here present the endoscopic treatment of a prenatally diagnosed quadrigeminal arachnoid cyst type III1 with right lateral extension into the middle cerebral fossa, and associated hydrocephalus, treated at the age of 18 mo.Step-by-step detail of surgical technique is presented in original anatomic conditions. Restoration of better cerebrospinal fluid pathways being the objective of this surgery, ventriculocystic, and cyst-cisternal fenestrations were made. Secondary obstruction of the cyst occurred a few months later, requiring further endoscopic treatment to obtain a larger fenestration that allowed good long-term clinical and radiological outcome. The key point of this video is to compare the 2 procedures, stressing the importance of the dimension of fenestrations, to ensure a long-term patency of both stomas.The patient being a child, both parents gave their consent for publication and signed a form. PMID- 29788186 TI - Nanoparticle-Based Oral Drug Delivery Systems Targeting the Colon for Treatment of Ulcerative Colitis. AB - 10.1093/ibd/izy123_video1izy123.video15786481867001. PMID- 29788190 TI - Benzodiazepines for Psychosis-Induced Aggression or Agitation. PMID- 29788189 TI - Progression of Mineral Ion Abnormalities in Patients With Jansen Metaphyseal Chondrodysplasia. AB - Context: Five different activating PTH/PTH-related peptide (PTHrP) receptor (PTHR1) mutations have been reported as causes of Jansen metaphyseal chondrodysplasia (JMC), a rare disorder characterized by severe growth plate abnormalities and PTH-independent hypercalcemia. Objectives: Assess the natural history of clinical and laboratory findings in 24 patients with JMC and characterize the disease-causing mutant receptors in vitro. Patients and Methods: The H223R mutation occurred in 18 patients. T410P, I458R and I458K each occurred in single cases; T410R was present in a father and his two sons. Laboratory records were analyzed individually and in aggregate. Results: Postnatal calcium levels were normal in most patients, but elevated between 0.15 and 10 years (11.8 +/- 1.37 mg/dL) and tended to normalize in adults (10.0 +/- 1.03 mg/dL). Mean phosphate levels were at the lower end of the age-specific normal ranges. Urinary calcium/creatinine (mg/mg) were consistently elevated (children, 0.80 +/- 0.40; adults, 0.28 +/- 0.19). Adult heights were well below the 3rd percentile for all patients, except for those with the T410R mutation. Most patients with JMC had undergone orthopedic surgical procedures, most had nephrocalcinosis, and two had advanced chronic kidney disease. The five PTHR1 mutants showed varying degrees of constitutive and PTH-stimulated cAMP signaling activity when expressed in HEK293 reporter cells. The inverse agonist [L11,dW12,W23,Y36]PTHrP(7-36) reduced basal cAMP signaling for each PTHR1 mutant. Conclusions: Except for T410R, the other PTHR1 mutations were associated with indistinguishable mineral ion abnormalities and cause similarly severe growth impairment. Hypercalciuria persisted into adulthood. An inverse agonist ligand effectively reduced in vitro PTH-independent cAMP formation at all five PTHR1 mutants, suggesting a potential path toward therapy. PMID- 29788191 TI - Functional characterization of WHY-WRKY75 transcriptional module in plant response to cassava bacterial blight. AB - Cassava is a major food crop in tropical areas, but its productivity and quality are seriously limited by cassava bacterial blight. So far, the key factors regulating cassava immune response remain elusive. In this study, we identified three cassava Whirly genes (MeWHYs) in cassava variety of South China 124 (SC124), and explored the possible roles and utilization of MeWHYs in cassava disease resistance. Gene expression analysis revealed that the transcripts of three MeWHYs were commonly regulated by the highly conserved N-terminal epitope of f lagellin (flg22) and Xanthomonas axonopodis pv. manihotis Hainan (Xam HN) treatments. Overexpression of MeWHYs improved plant disease resistance against X. axonopodis pv. manihotis, while MeWHYs-silenced cassava plants by virus-induced gene silencing exhibited decreased disease resistance. Notably, MeWRKY75 physically interacted with three MeWHYs in yeast and in planta, and served as a transcriptional activator of MeWHY3. Moreover, the physical interaction between MeWHYs and MeWRKY75 promoted the transcriptional activities of each other. Consistently, MeWRKY75 also positively regulated disease resistance against cassava bacterial blight. Taken together, our observations suggested that MeWRKY75 and MeWHYs confer improved disease resistance against cassava bacterial blight through forming an interacting complex of MeWRKY75-MeWHY1/2/3 and transcriptional module of MeWRKY75-MeWHY3. This study facilitates our understanding of the positive effect of the MeWRKY75-MeWHY3 transcriptional module in plant disease resistance. PMID- 29788192 TI - Initial Assessment of the Risk Assessment and Prediction Tool in a Heterogeneous Neurosurgical Patient Population. AB - BACKGROUND: Bundled care payments are increasingly being explored for neurosurgical interventions. In this setting, skilled nursing facility (SNF) is less desirable from a cost perspective than discharge to home, underscoring the need for better preoperative prediction of postoperative disposition. OBJECTIVE: To assess the capability of the Risk Assessment and Prediction Tool (RAPT) and other preoperative variables to determine expected disposition prior to surgery in a heterogeneous neurosurgical cohort, through observational study. METHODS: Patients aged 50 yr or more undergoing elective neurosurgery were enrolled from June 2016 to February 2017 (n = 623). Logistic regression was used to identify preoperative characteristics predictive of discharge disposition. Results from multivariate analysis were used to create novel grading scales for the prediction of discharge disposition that were subsequently compared to the RAPT Score using Receiver Operating Characteristic analysis. RESULTS: Higher RAPT Score significantly predicted home disposition (P < .001). Age 65 and greater, dichotomized RAPT walk score, and spinal surgery below L2 were independent predictors of SNF discharge in multivariate analysis. A grading scale utilizing these variables had superior discriminatory power between SNF and home/rehab discharge when compared with RAPT score alone (P = .004). CONCLUSION: Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. These tools may identify patients who may benefit from expedited discharge to subacute care facilities and decrease inpatient hospital resource utilization following surgery. PMID- 29788193 TI - Ocular toxoplasmosis: adverse reactions to treatment in a Brazilian cohort. AB - Background: The purpose of this study was to estimate the frequency and describe the adverse drug reactions (ADRs) associated with the classic treatment of ocular toxoplasmosis (OT), namely sulfadiazine, pyrimethamine, corticosteroids and folinic acid. Methods: We performed a descriptive study of a prospective cohort of patients with OT treated with the classic therapy. Data were collected during medical consultations and treatment. Results: Of the 147 patients studied, 85% developed one or more ADR. Women presented more ADRs than men (95% vs 77%). Of the total reactions (n=394), 82% were mild, but we found one life-threatening event (Stevens-Johnson syndrome). The most frequent types (71%) of ADRs were gastrointestinal, skin and neurological or psychiatric. The majority of ADRs (90.3%) occurred before the second week of treatment. A third of the patients were treated for the ADR and 10% dropped out of OT treatment. Most (70%) of the ADRs were characterized as being probably caused by the drugs and may be associated with prednisone, sulfadiazine and sulfadiazine/prednisone. Six percent of ADRs were not previously described, such as taste alteration, constipation/bloating, dyspnoea, sweating and somnolence. Conclusions: Our results suggest a high rate of ADRs to OT classic treatment, which requires careful follow-up in order to identify and treat ADRs early. PMID- 29788194 TI - A project to assess the quality of the published guidelines for managing primary spontaneous pneumothorax from the Italian Society of Thoracic Surgeons. AB - OBJECTIVES: A project to assess the existing literature and the quality of past guidelines on the management of primary spontaneous pneumothorax was developed by the Italian Society of Thoracic Surgeons, with particular focus on the assessment of the methods used to produce such recommendations. METHODS: The different items and domains within each guideline were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and scored on a 7-point scale. RESULTS: Five guidelines matched the inclusion criteria and were assessed. A multinational collaboration produced 2 of 5 guidelines. The observers recommended (with modifications) only 2 guidelines. Clarity of presentation, scope and purpose (objectives and health questions target the population) received the best score, whereas the applicability of the guideline received the lowest score. International development positively influenced the scope and purpose of the guidelines. Moreover, improved scores were achieved when the stakeholders were fully involved and had editorial independence. CONCLUSIONS: As assessed by the AGREE II criteria, the quality of the various guidelines was extremely inconsistent. Guidelines with higher AGREE II scores were those developed with the participation of European scientific societies. PMID- 29788195 TI - ESWR1-CREM Fusion in an Intracranial Myxoid Angiomatoid Fibrous Histiocytoma-Like Tumor: A Case Report and Literature Review. AB - Gene fusions of EWSR1 with members of the CREB family of transcription factors (CREB1, ATF1, and CREM) have recently been described in exceptional intracranial myxoid mesenchymal tumors. Although this is a known gene fusion found in various mesenchymal tumors, EWSR1 fusion with CREM has only been observed in 3 intracranial myxoid tumors. In this paper, we present 1 such tumor with in-depth histopathological description and long-term follow-up. There is controversy regarding whether these tumors represent a novel entity or simply an intracranial localization of the myxoid variant of angiomatoid fibrous histiocytoma, a rare soft tissue tumor of the extremities. Out of 11 cases mentioned in the literature, the 3 isolated case reports by Dunham et al, Ochalski et al, and Alshareef et al are designated as angiomatoid fibrous histiocytoma, whereas the others are defined as a novel tumoral entity called intracranial myxoid mesenchymal tumor with EWSR1-CREB fusion. We believe the vast morphological and immunohistochemical spectrum of angiomatoid fibrous histiocytoma makes it difficult to dismiss this diagnosis. PMID- 29788198 TI - Venous Thromboembolism After Intraventricular Hemorrhage: Results From the CLEAR III Trial. AB - BACKGROUND: Venous thromboembolism (VTE) after intracerebral hemorrhage is well studied, but data on patients with spontaneous intraventricular hemorrhage (IVH) are limited. OBJECTIVE: To study the factors associated with VTE, association between VTE and clinical outcomes in IVH, and safety of VTE chemoprophylaxis in IVH treated with intraventricular catheters and thrombolysis. METHODS: Retrospective cohort study of patients enrolled in the CLEAR III trial, a multicenter, randomized trial comparing external ventricular drainage, with administration of intraventricular alteplase vs placebo, for obstructive IVH. Predictor variable was incident VTE in the first 30 d. Outcome measures were factors associated with VTE, and death/severe disability (modified Rankin Score 4 6) at 6 mo. RESULTS: Of the 500 patients with IVH, VTE occurred in 59 patients (11.8%) within the first 30 d. VTE chemoprophylaxis was initiated in 412 (82.4%) patients, but before VTE diagnosis in only 401 (80.2%) at median of 4 d (interquartile range, 1-8) from IVH onset, and was not associated with intracranial bleeding or catheter tract hemorrhage. In the multivariate logistic regression analysis, infection within 30 d (odds ratio, 1.80; confidence interval, 1.03-3.17) was significantly associated with higher odds of VTE occurrence. Starting VTE chemoprophylaxis after 72 h was additionally associated with VTE occurrence after the first week. CONCLUSION: Infection and delay in timely initiation of VTE chemoprophylaxis were associated with VTE occurrence. VTE chemoprophylaxis in IVH appears safe and should not be delayed beyond standard care policies for ICH including when intraventricular catheter placement and thrombolytic therapy are performed. PMID- 29788196 TI - Maternal Weight, Snoring, and Hypertension: Potential Pathways of Associations. AB - BACKGROUND: Hypertensive disorders of pregnancy (HDP) are linked to excessive maternal weight and frequent snoring. However, pathways between maternal excessive weight, pregnancy-onset snoring, and HDP are only partially estimated. We examined and quantified the total and direct associations between excessive maternal weight and incident HDP and their indirect pathway through pregnancy onset snoring. METHODS: Third trimester pregnant women enrolled from prenatal clinics of a large tertiary medical center. Sleep data were collected through a questionnaire. Demographic and pregnancy information and first trimester maternal weight were abstracted from medical charts. After exclusion of women with prepregnancy hypertension and/or chronic snoring, causal mediation analysis was used to estimate the total and direct association between maternal weight and incident HDP and their indirect association through pregnancy-onset snoring. The proportion of the mediated association through pregnancy-onset snoring from the total association of maternal weight and HDP was also quantified. RESULTS: After excluding those with chronic hypertension and/or snoring, the final sample included 1,333 pregnant women. In adjusted analysis, excessive maternal weight was directly associated with incident HDP; odds ratio (OR) = 1.87 (95% confidence interval (CI) 1.30, 2.70). Pregnancy-onset snoring significantly mediated the association between maternal weight and incident HDP; OR = 1.08 (95% CI 1.01, 1.17). The mediated pathway accounted for 15% of the total association between maternal weight and incident HDP. CONCLUSIONS: Pregnancy-onset snoring mediates the association between maternal weight and incident HDP in women without prepregnancy snoring or hypertension. These findings demonstrate the relative contributions of excessive maternal weight and pregnancy-onset snoring to incident HDP. PMID- 29788197 TI - Surrogate Preferences on the Physician Orders for Life-Sustaining Treatment Form. AB - Background and Objectives: The purpose of this study is to compare treatment preferences of patients to those of surrogates on the Physician Orders for Life Sustaining Treatment (POLST) forms. Research Design and Methods: Data were collected from a sequential selection of 606 Massachusetts POLST (MOLST) forms at 3 hospitals, and corresponding electronic patient health records. Selections on the MOLST forms were categorized into All versus Limit Life-Sustaining Treatment. Multivariable mixed effects (grouped by clinician) logistic regression models estimated the impact of using a surrogate decision maker on choosing All Treatment, controlling for patient characteristics (age, severity of illness, sex, race/ethnicity), clinician (physician vs non-physician), and hospital (site). Results: Surrogates signed 253 of the MOLSTs (43%). A multivariable logistic regression model taking into consideration patient, clinician, and site variables showed that surrogate decision makers were 60% less likely to choose All Treatment than patients who made their own decisions (odds ratio = 0.39 [95% confidence interval = 0.24-0.65]; p < .001). This model explained 44% of the variation in the dependent variable (Pseudo-R2 = 0.442; p < .001); mixed effects logistic regression grouped by clinician showed no difference between the models (LR test = 4.0e-13; p = 1.00). Discussion and Implications: Our study took into consideration variation at the patient, clinician, and site level, and showed that surrogates had a propensity to limit life-sustaining treatment. Surrogate decision makers are frequently needed for hospitalized patients, and nearly all states have adopted the POLST. Researchers may want study decision-making processes for patients versus surrogates when the POLST paradigm is employed. PMID- 29788199 TI - Influences of trace mineral nutrition and maternal flock age on broiler embryo bone development. AB - At hatch, the chick skeleton is a miniature of that of the adult bird. The hen deposits calcium, phosphorus, and trace minerals (copper, zinc, and manganese) along with vitamin D into the egg to allow development of the embryonic skeleton. The main source of calcium is the eggshell, whereas phosphorus, trace minerals, and vitamin D are mainly derived from the yolk. Calcium is absorbed from the eggshell and transferred to the embryo and yolk through the chorioallantoic membrane, whereas phosphorus and trace minerals are simultaneously mobilized by the yolk sac membrane. These processes start at day 12 of incubation and peak at around day 17. While the eggshell provides a steady supply of calcium until 19 d of incubation, phosphorus and trace mineral reserves decrease considerably and minimal skeletal development occurs in the last 3 d of incubation. Whether the low levels of phosphorus and trace minerals at late incubation prevent further bone growth, or some other biological control exists preventing further mineralization towards hatching is unknown. Maternal transfer of minerals and the influence of trace mineral form in the hen diet to advance the state of skeletal development at hatch have received increased research attention. Minimal effects on yolk mineral composition and bone growth were observed in the offspring of hens fed different forms of trace minerals. Embryos from young hens had inferior bone development towards the end of incubation and at hatch relative to chicks from older hens. This effect is likely a consequence of limited egg nutrient resources in eggs from young hens. The influence of maternal nutrient transfer on embryonic bone development has been clearly established. However, attempts to increase the state of skeletal development at hatch through increasing egg mineral content have met with limited success. The focus of this paper is the relationship between skeletal mineralization of the chicken embryo throughout incubation and egg mineral supply. PMID- 29788200 TI - Mycoplasma pneumoniae as a Cause of Community-Acquired Pneumonia in Children. PMID- 29788201 TI - Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons. AB - The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro. Loss of one Cntnap2 allele is sufficient to elicit axonal growth alteration, revealing a situation that may be relevant for CNTNAP2 heterozygosity in ASD patients. Then, we show that the two ASD variants I869T and G731S, which present impaired binding to Contactin2/TAG-1, do not rescue axonal growth deficits. We find that the variant R1119H leading to protein trafficking defects and retention in the endoplasmic reticulum has a dominant-negative effect on heterozygous Cntnap2 cortical neuron axon growth, through oligomerization with wild-type Caspr2. Finally, we identify an additional variant (N407S) with a dominant-negative effect on axon growth although it is well-localized at the membrane and properly binds to Contactin2. Thus, our data identify a new neurodevelopmental function for Caspr2, the dysregulation of which may contribute to clinical manifestations of ASD, and provide evidence that CNTNAP2 heterozygous missense variants may contribute to pathogenicity in ASD, through selective mechanisms. PMID- 29788202 TI - Quantitative proteomics reveals neuronal ubiquitination of Rngo/Ddi1 and several proteasomal subunits by Ube3a, accounting for the complexity of Angelman syndrome. AB - Angelman syndrome is a complex neurodevelopmental disorder caused by the lack of function in the brain of a single gene, UBE3A. The E3 ligase coded by this gene is known to build K48-linked ubiquitin chains, a modification historically considered to target substrates for degradation by the proteasome. However, a change in protein abundance is not proof that a candidate UBE3A substrate is indeed ubiquitinated by UBE3A. We have here used an unbiased ubiquitin proteomics approach, the bioUb strategy, to identify 79 proteins that appear more ubiquitinated in the Drosophila photoreceptor cells when Ube3a is over-expressed. We found a significantly high number of those proteins to be proteasomal subunits or proteasome-interacting proteins, suggesting a wide proteasomal perturbation in the brain of Angelman patients. We focused on validating the ubiquitination by Ube3a of Rngo, a proteasomal component conserved from yeast (Ddi1) to humans (DDI1 and DDI2), but yet scarcely characterized. Ube3a-mediated Rngo ubiquitination in fly neurons was confirmed by immunoblotting. Using human neuroblastoma SH-SY5Y cells in culture, we also observed that human DDI1 is ubiquitinated by UBE3A, without being targeted for degradation. The novel observation that DDI1 is expressed in the developing mice brain, with a significant peak at E16.5, strongly suggests that DDI1 has biological functions not yet described that could be of relevance for Angelman syndrome clinical research. PMID- 29788203 TI - Do cost containment policies save money and influence physicians' prescribing behavior? Lessons from South Korea's drug policy for diabetes medication. AB - Objective: We evaluate the effects of drug price reduction policy on pharmaceutical expenditure and prescription patterns in diabetes medication. Design: An interrupted time series study design using generalized estimating equations. Setting: This study used National Health Insurance claim data from 2010 to 2013. Participants: A total of 68 127 diabetes patients and 12 465 hospitals. Intervention(s): The drug price reduction policy. Main Outcome Measures: The primary outcome is pharmaceutical expenditure and prescription rate. To evaluate changes in prescription rate, we measured prescription rates such a brand-name drug and drug price reduction rate. Results: Although the drug price reduction policy associated with decreased pharmaceutical expenditure ( 13.22%, P < 0.0001), the trend (-0.01%, P = 0.9201) did not change significantly compared with the pre-intervention period. In addition, the trends in the monthly prescription rate of brand-name drugs decreased (-0.14%, P = 0.0091), while the immediate change was an increase (5.72%, P < 0.0001). Regardless of the drug reduction rate, the prescription rate after the introduction of the drug price reduction policy decreased compared with the pre-intervention period, and this decline was significant for reduction rates of 0% (-2.74%, P < 0.0001) and 10% ( 0.13%, P = 0.0018). Conclusions: Our results provide evidence of the effects of the drug price reduction policy on pharmaceutical expenditure and prescription patterns. This policy did not affect the prescribing behavior of healthcare providers and did not increase the use of drugs not subject to this policy. Although this study did not observe changes in the cost of pharmaceuticals after the introduction of the drug price reduction policy, further research is needed on the long-term changes in such costs. PMID- 29788204 TI - Rabies Antibody Response After Booster Immunization: A Systematic Review and Meta analysis. AB - Although fatal once symptomatic, rabies is preventable by administration of pre- and post-exposure vaccines. International guidelines suggest lifelong protection by a pre-exposure vaccination scheme followed by timely post-exposure vaccines. Rapidity and magnitude of the antibody recall response after booster inoculation are essential, as many people have been previously immunized a long time ago. The objective of this study was therefore to systematically review the evidence on the boostability of rabies immunization to date. We included 36 studies, of which 19 studies were suitable for meta-analysis. Reduced antibody levels were found after intradermal primary schedules as compared to intramuscular schedules. However, responses after booster immunization were adequate for both routes. Although studies showed that antibody levels decline over time, adequate booster responses were still retained over long time intervals indicating that post exposure treatment is effective without extra measures after long periods of time. PMID- 29788205 TI - The impact of vaccination route on Mycoplasma gallisepticum vaccine efficacy. AB - Mycoplasma gallisepticum infection can lead to major financial losses for poultry producers. Control of M. gallisepticum infection in the layer industry is generally obtained through vaccination due to the nature of the multi-aged flocks in the facilities. Live vaccines can provide significant protection from the pathogenic effects of M. gallisepticum infection. However, differing management practices, including vaccination procedures, can lead to significant variations in the efficacy of the same vaccine. The site of vaccine deposition has been shown to be one important factor significantly influencing the vaccination outcome. Previous research has shown that vaccine applied to the eyes or sprayed on the head is significantly more effective than when sprayed on the body. Vaccine application to the eyes, through the nares (nasal), and 2 routes through the oral cavity were studied to further characterize the most efficient route for delivery. Results of this work demonstrate that eye drop vaccination is significantly more effective than nasal vaccination, and vaccine delivered through the oral cavity has a negligible contribution to overall vaccination outcome. PMID- 29788206 TI - Deletion of PBP1a/LpoA complex compromises cell envelope integrity in Shewanella oneidensis. AB - High molecular weight penicillin-binding proteins (PBPs) are responsible for the biosynthesis of peptidoglycan. In Escherichia coli, PBP1a and PBP1b form multienzyme peptidoglycan-synthesizing complexes with outer membrane lipoproteins LpoA and LpoB, respectively. The two complexes appear to be largely redundant, although their distinct physiological roles remain unclear. PBP1a/LpoA and PBP1b/LpoB also exist in Shewanella oneidensis strain MR-1, but effects of the two complexes on aerobic growth and beta-lactam resistance are quite different. In this study, the phenotypes of strains lacking a certain complex in S. oneidensis were compared. Deletion of PBP1a/LpoA caused aberrant cell morphology (including branches and bulges), enhanced sensitivity to various envelope stresses and outer membrane permeability. On the contrary, strains lacking PBP1b/LpoB displayed phenotypes similar to the wild type. PMID- 29788207 TI - Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain. AB - Hsp104 is a hexameric AAA + ATPase and protein disaggregase found in yeast, which can be potentiated via mutations in its middle domain (MD) to counter toxic phase separation by TDP-43, FUS and alpha-synuclein connected to devastating neurodegenerative disorders. Subtle missense mutations in the Hsp104 MD can enhance activity, indicating that post-translational modification of specific MD residues might also potentiate Hsp104. Indeed, several serine and threonine residues throughout Hsp104 can be phosphorylated in vivo. Here, we introduce phosphomimetic aspartate or glutamate residues at these positions and assess Hsp104 activity. Remarkably, phosphomimetic T499D/E and S535D/E mutations in the MD enable Hsp104 to counter TDP-43, FUS and alpha-synuclein aggregation and toxicity in yeast, whereas T499A/V/I and S535A do not. Moreover, Hsp104T499E and Hsp104S535E exhibit enhanced ATPase activity and Hsp70-independent disaggregase activity in vitro. We suggest that phosphorylation of T499 or S535 may elicit enhanced Hsp104 disaggregase activity in a reversible and regulated manner. PMID- 29788208 TI - The TORC1-Sch9 pathway as a crucial mediator of chronological lifespan in the yeast Saccharomyces cerevisiae. AB - The concept of ageing is one that has intrigued mankind since the beginning of time and is now more important than ever as the incidence of age-related disorders is increasing in our ageing population. Over the past decades, extensive research has been performed using various model organisms. As such, it has become apparent that many fundamental aspects of biological ageing are highly conserved across large evolutionary distances. In this review, we illustrate that the unicellular eukaryotic organism Saccharomyces cerevisiae has proven to be a valuable tool to gain fundamental insights into the molecular mechanisms of cellular ageing in multicellular eukaryotes. In addition, we outline the current knowledge on how downregulation of nutrient signaling through the target of rapamycin (TOR)-Sch9 pathway or reducing calorie intake attenuates many detrimental effects associated with ageing and leads to the extension of yeast chronological lifespan. Given that both TOR Complex 1 (TORC1) and Sch9 have mammalian orthologues that have been implicated in various age-related disorders, unraveling the connections of TORC1 and Sch9 with yeast ageing may provide additional clues on how their mammalian orthologues contribute to the mechanisms underpinning human ageing and health. PMID- 29788209 TI - Musculoskeletal Injuries Among Female Soldiers Working With Dogs. AB - Introduction: Female soldiers serving in the Israeli Defense Forces canine unit may be at increased risk of overuse injuries related to working with military dogs. We hypothesized that this particular type of occupational exposure may lead to an increased strain of the upper extremity due to such non-physiologic motions as pulling the dog's strap or resisting the sudden pulling by the dog, and may result in an increased rate of overuse injuries. Materials and Methods: We compared incidence of overuse injuries in a retrospective cohort of female soldiers who served either in the military working dogs' unit (MWD), or in the light infantry battalions (Infantry) from 2005 to 2015. We compared injury incidence of both groups during two periods: 5 mo of basic training (neither worked with dogs) and 19 or more months of combat service. Incidence was calculated as number of diagnoses per person-months (rate ratios, RR); each diagnosis counted once per study subject. We used RR confidence intervals to compare incidence of injuries between groups. Results: There were 3,443 person months in the MWD group and 194,590 person-months in the Infantry group. There was no difference in injury incidence between groups during the initial period of basic training. During the second period, MWDs had higher incidence of upper limb (RR = 1.45, p = 0.048) and hip (RR = 3.6, p < 0.0001) injuries. The association between service with dogs and upper limb injuries remained significant (RR = 1.09, p = 0.005) after adjusting for confounding variables in the multivariate regression analysis. Other independent predictors of the upper limb overuse injuries included each additional month of service (RR = 1.003, p = 0.008), Eastern European origin compared with Israeli-born recruits (RR = 0.97, p = 0.03), increased body weight in increments of 10 kg (RR = 1.008, p = 0.03), anemia (RR = 1.02, p = 0.02) and fatigue (RR = 1.05, p <= 0.0001). Conclusions: We found that service in the MWD unit was associated with increased risk of upper limb injuries. Identification of the exact mechanism of injury and targeted interventions, as well as treatment of anemia and fatigue may lead to reduction of injuries in this unit. PMID- 29788212 TI - Yogurt Intake and Risk of Cardiovascular Disease Among Hypertensive Individuals: Is It Time for a Clinical Trial? PMID- 29788211 TI - Particle Concentrations in Occupational Settings Measured with a Nanoparticle Respiratory Deposition (NRD) Sampler. AB - There is an increasing need to evaluate concentrations of nanoparticles in occupational settings due to their potential negative health effects. The Nanoparticle Respiratory Deposition (NRD) personal sampler was developed to collect nanoparticles separately from larger particles in the breathing zone of workers, while simultaneously providing a measure of respirable mass concentration. This study compared concentrations measured with the NRD sampler to those measured with a nano Micro Orifice Uniform-Deposit Impactor (nanoMOUDI) and respirable samplers in three workplaces. The NRD sampler performed well at two out of three locations, where over 90% of metal particles by mass were submicrometer particle size (a heavy vehicle machining and assembly facility and a shooting range). At the heavy vehicle facility, the mean metal mass concentration of particles collected on the diffusion stage of the NRD was 42.5 +/- 10.0 ug/m3, within 5% of the nanoMOUDI concentration of 44.4 +/- 7.4 ug/m3. At the shooting range, the mass concentration for the diffusion stage of the NRD was 5.9 ug/m3, 28% above the nanoMOUDI concentration of 4.6 ug/m3. In contrast, less favorable results were obtained at an iron foundry, where 95% of metal particles by mass were larger than 1 um. The accuracy of nanoparticle collection by NRD diffusion stage may have been compromised by high concentrations of coarse particles at the iron foundry, where the NRD collected almost 5-fold more nanoparticle mass compared to the nanoMOUDI on one sampling day and was more than 40% different on other sampling days. The respirable concentrations measured by NRD samplers agreed well with concentrations measured by respirable samplers at all sampling locations. Overall, the NRD sampler accurately measured concentrations of nanoparticles in industrial environments when concentrations of large, coarse mode, particles were low. PMID- 29788210 TI - Carbonyl Reduction of NNK by Recombinant Human Lung Enzymes. Identification of HSD17beta12 as the Reductase important in (R)-NNAL formation in Human Lung. AB - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most abundant and carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke. The major metabolic pathway for NNK is carbonyl reduction to form the (R) and (S) enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which, like NNK, is a potent lung carcinogen. The goal of the present study was to characterize NNAL enantiomer formation in human lung and identify the enzymes responsible for this activity. While (S)-NNAL was the major enantiomer of NNAL formed in incubations with NNK in lung cytosolic fractions, (R)-NNAL comprised ~60 and ~95% of the total NNAL formed in lung whole cell lysates and microsomes, respectively. In studies examining the role of individual recombinant reductase enzymes in lung NNAL enantiomer formation, AKR1C1, AKR1C2, AKR1C3, AKR1C4 and CBR1 all exhibited (S)-NNAL formation activity. To identify the microsomal enzymes responsible for (R)-NNAL formation, 28 microsomal reductase enzymes were screened for expression by real-time PCR in normal human lung. HSD17beta6, HSD17beta12, KDSR, NSDHL, RDH10, RDH11 and SDR16C5 were all expressed at levels >HSD11beta1, the only previously reported microsomal reductase enzyme with NNK reducing activity, with HSD17beta12 the most highly expressed. Of these lung expressing enzymes, only HSD17beta12 exhibited activity against NNK, forming primarily (>95%) (R)-NNAL, a pattern consistent with that observed in lung microsomes. siRNA knockdown of HSD17beta12 resulted in significant decreases in (R)-NNAL formation activity in HEK293 cells. These data suggest that both cytosolic and microsomal enzymes are active against NNK and that HSD17beta12 is the major active microsomal reductase that contributes to (R)-NNAL formation in human lung. PMID- 29788213 TI - Carcass and meat quality of dual-purpose chickens (Lohmann Dual, Belgian Malines, Schweizerhuhn) in comparison to broiler and layer chicken types. AB - Currently, there is an intensive ethical discussion about the practice of culling day-old layer cockerels. One solution to avoid this practice could be using dual purpose types, where males are fattened for meat and females used for egg production. The aim of the present study was to compare fattening performance, carcass conformation, and composition as well as meat quality of Lohmann Dual, a novel dual-purpose type, and 2 traditional dual-purpose types (Belgian Malines and Schweizerhuhn) with 2 broiler types and 1 layer type (Lohmann Brown Plus). Broilers included a conventional line (Ross PM3) and a slower-growing line (Sasso 51) fulfilling requirements of organic farming. Nine birds of each type were fed on a conventional broiler diet. Feed intake and metabolizability of nitrogen and energy were recorded per pen (n = 3), the latter through excreta sampling. For each bird, carcass conformation was assessed, and weights of body, carcass, breast meat, legs, wings, and inner organs were determined. Additionally, breast angle, an indicator for carcass appeal, and skin color were recorded. Meat quality assessment included determinations of thaw and cooking loss, shear force, meat color, and proximate composition of the breast meat. None of the dual purpose types (20 to 30 g ADG) performed as well in growth as the intensively growing broiler line (68 g ADG). However, Lohmann Dual could compete with the slower-growing broiler line (slower growth but better feed efficiency, similar in carcass weight and breast proportion). Also breast angle was quite similar between Lohmann Dual (100 degrees ) and the extensive broiler type (115 degrees C) compared to the intensive broiler line (180 degrees ). Meat quality was most favorable in the intensive broilers with the smallest shear force and thawing loss, whereas meat quality was not different between the other types. The Schweizerhuhn performed only at the level of the layer hybrid, and the Belgian Malines was ranked only slightly better. PMID- 29788214 TI - Treatment Failure of TNF-alpha Inhibitors in Obese Patients With Inflammatory Bowel Disease-A Cohort Study. AB - Background: In treatment of inflammatory bowel disease (IBD) with anti-tumor necrosis factor-alpha agents (anti-TNF-alpha), obesity has been suspected as a cause of accelerated loss of response (LOR). We sought to determine whether overweight IBD patients have accelerated LOR when treated with anti-TNF-alpha agents, compared with normal weight IBD patients. Methods: We identified a cohort of adult IBD patients treated with anti-TNF-alpha agents at a Danish university hospital. Patients were grouped according to body mass index (BMI), and our main outcome was time to LOR. We performed survival analyses on LOR and calculated hazard ratios (HRs) with the normal weight group as the reference, while adjusting for confounders. Results: Of 210 eligible patients, 92 (44%) experienced LOR. One hundred eighty patients were treated with infliximab and 30 with adalimumab, 114 (54%) were normal weight, 51 (24%) were overweight, and 45 (21%) were obese. Regression analysis produced the following adjusted HRs, compared with the normal weight group: overweight 0.89 (95% confidence interval [CI], 0.51-1.56) and obese 1.31 (95% CI, 0.76-2.24), thus showing no statistically significant association between BMI and time to LOR. Subgroup analyses produced similar results, except for obese ulcerative colitis patients having an adjusted HR of 2.42 (95% CI, 1.03-5.70). Conclusions: In IBD patients treated with anti-TNF-alpha agents, we found no overall association between increased BMI and accelerated LOR. PMID- 29788215 TI - An Unusual Presentation of Murine Typhus and Mononucleosis. AB - A 20-year-old female presented to the emergency department complaining of fever, cough, and dyspnea after a recent camping trip. The patient remained ill appearing, persistently tachycardic and dyspneic despite nebulizer treatments, and fluids in the emergency department. She was admitted for observation and gradually improved over the next 4 d. Inpatient laboratory studies indicated acute Epstein-Barr virus infection and she was discharged with a presumptive diagnosis of infectious mononucleosis. However, further testing showed a simultaneous rickettsial infection producing murine typhus. The patient ultimately recovered uneventfully once proper treatment was initiated. This patient's presentation represents a unique description of simultaneous infectious mononucleosis and murine typhus which underscores the importance of maintaining a broad differential diagnosis in the approach to febrile illnesses. PMID- 29788216 TI - Do nano-particles cause recalcitrant vulnerability curves in Robinia? Testing with a four-cuvette Cochard rotor and with water extraction curves. AB - Cavitation resistance is a key trait for characterizing the drought adaption in plants and is usually presented in terms of vulnerability curves. Three principal techniques have been developed to produce vulnerability curves, but curves generated with centrifugation are reported to suffer from artifacts when applied to long-vesseled species. The main cause of this artifact is the issue of open vessels, resulting in a nano-particle effect that may seed premature embolism. We used two methods to test the potential mechanism behind the nano-particle effect in centrifuge-based vulnerability curves. A four-cuvette rotor system based on a traditional Cochard rotor was designed to inhibit effervescence while injecting water, but the recalcitrant vulnerability curves in Robinia could not be eliminated. There may be multiple sources, besides effervescence, of hypothetical nano-particles: they may arise from cut surfaces or they may be always present in the injected water, leading to the premature embolisms. To prevent the entry of the hypothetical nano-particles, water extraction curves in terms of PLV (percentage loss volume of extracted water from stems) vs tensions were constructed. The PLV curves of Robinia showed s-shaped characteristics after subtracting the first Weibull components from water extraction curves, which were not related to the water loss from vessels according to dye staining experiments. The differences between T50 (xylem tension at which 50% of hydraulic conductivity is lost) in mean PLV curve and T50 in percentage loss of conductivity curves determined by the four-cuvette rotor system and by the bench dehydration method were 3.9 MPa and 0.7 MPa, respectively. Hence, PLV curves may be a valid way to measure the cavitation resistance in long-vesseled species with centrifugation. Keeping bark intact in the process of measurement is recommended, otherwise it would increase evaporation from the entire system. PMID- 29788217 TI - Treatment-Free Survival in Patients With Differentiated Thyroid Cancer. AB - Objective: Cancer recurrence is a primary concern for patients with differentiated thyroid cancer; however, population-level data on recurrent or persistent disease do not currently exist. The objective of this study was to determine treated recurrent or persistent thyroid cancer by using a population based registry, identify correlates of poor treatment-free survival, and define prognostic groups for treatment-free survival. Methods: In this population-based study, we evaluated treatment-free survival in 9273 patients from the Surveillance, Epidemiology, and End Results Program-Medicare with a diagnosis of differentiated thyroid cancer between 1998 and 2012. Treated recurrence was defined by treatment of recurrent or persistent differentiated thyroid cancer with surgery, radioactive iodine, or radiation therapy at >=1 year after diagnosis. Multivariable analysis was performed with Cox proportional hazards regression, survival trees, and random survival forests. Results: In this cohort the median patient age at time of diagnosis was 69 years, and 75% of the patients were female. Using survival tree analyses, we identified five distinct prognostic groups (P < 0.001), with a prediction accuracy of 88.7%. The 5-year treatment free survival rates of these prognostic groups were 96%, 91%, 85%, 72%, and 52%, respectively, and the 10-year treatment-free survival rates were 94%, 87%, 80%, 64%, and 39%. Based on survival forest analysis, the most important factors for predicting treatment-free survival were stage, tumor size, and receipt of radioactive iodine. Conclusion: In this population-based cohort, five prognostic groups for treatment-free survival were identified. Understanding treatment-free survival has implications for the care and long-term surveillance of patients with differentiated thyroid cancer. PMID- 29788218 TI - Evolution of the Randomized Controlled Trial in Inflammatory Bowel Disease: Current Challenges and Future Solutions. AB - As knowledge of the pathogenesis of inflammatory bowel disease (IBD) has grown, many new medical therapies have become available. Evaluation of the efficacy and safety of new drugs has conventionally been established with placebo-controlled randomized trials. However, given that highly effective and safe biologic agents such as tumor necrosis factor (TNF) antagonists, vedolizumab, and ustekinumab are currently available, the continued use of placebo-controlled studies to evaluate new molecules should be questioned. Although alternate study designs are available, their implementation presents multiple challenges that need to be overcome. Other challenges in the current investigative landscape include poor recruitment rates, enrollment of highly refractory patients, and substantial changes in the regulatory standards required for drug approval. In this article, we present an overview of these challenges and discuss potential solutions with an emphasis on implications for the practicing clinician. PMID- 29788220 TI - Obstructive Sleep Apnea Syndrome and Metabolic Diseases. AB - With the rapid changes in lifestyle in modern society, including the high nutritional intake and reduced physical activity, the incidence of metabolic diseases has been increasing year by year. Obstructive sleep apnea syndrome (OSAS) is a sleep disorder, usually characterized by sudden pauses of breathing during sleep and an interrupted sleep rhythm. Although the pathological mechanism remains poorly understood, it has been strongly associated with metabolic diseases, including obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD). In the present mini-review, we briefly summarize the connections between OSAS, obesity, T2DM, and NAFLD, which might help us to better understand the pathogenesis of human diseases. PMID- 29788219 TI - Exploiting metamerism to regulate the impact of a visual display on alertness and melatonin suppression independent of visual appearance. AB - Objectives: Artificial light sources such as visual display units (VDUs) elicit a range of subconscious and reflex light responses, including increases in alertness and suppression of pineal melatonin. Such responses employ dedicated retinal circuits encompassing melanopsin photoreceptors. Here, we aimed to determine whether this arrangement can be exploited to modulate the impact of VDUs on melatonin onset and alertness without altering visual appearance. Methods: We generated a five-primary VDU capable of presenting metameric movies (matched for color and luminance) but varying in melanopic-irradiance. Healthy human participants (n = 11) were exposed to the VDU from 18:00 to 23:00 hours at high- or low-melanopic setting in a randomized cross-over design and measured salivary melatonin and self-reported sleepiness at 30-minute intervals. Results: Our VDU presented a 3* adjustment in melanopic-irradiance for images matched photometrically for color and luminance. Participants reported no significant difference in visual appearance (color and glare) between conditions. During the time in which the VDU was viewed, self-reported sleepiness and salivary melatonin levels increased significantly, as would be expected in this phase of the diurnal cycle. The magnitude of the increase in both parameters was significantly enhanced when melanopic-irradiance was reduced. Conclusions: Our data demonstrate that melatonin onset and self-reported sleepiness can be modulated independent of photometric parameters (color and luminance) under a commonly encountered light exposure scenario (evening use of a VDU). They provide the first demonstration that the impact of light on alertness and melatonin production can be controlled independently of visual experience, and establish a VDU capable of achieving this objective. PMID- 29788221 TI - Predictive factors of life quality among packaging workers in Taiwan. AB - The semiconductor plants on the top of high-tech industrial chain hire many packaging workers to carry out miscellaneous packing tasks for various product orders from different companies and countries. Under tremendous workload the quality of life (QoL) of such packaging workers need to be concerned. The aim of this study was to explore factors influencing their QoL. This study recruited 247 packing workers (162 male and 85 female; mean age: 35.6 years old) in 2015 and 2016 from a semiconductor plant in Taiwan by convenience sampling. The questionnaire comprised four parts: demographics, the World Health Organization Quality of Life (WHOQOL-BREF), an occupational burnout inventory and the Nordic Musculoskeletal Questionnaire. The four domains of the WHOQOL-BREF were defined as outcome variables. Predictive factors included gender (reference: male), age (reference: <= 35), BMI (reference: <= 25), educational level (reference: below university), marital/partner status (reference: married/cohabiting), years of work (reference: <= 5), work shift (reference: day shift), personal burnout, work related burnout, over-commitment to work and the number of body parts with discomfort (0-9). The findings showed that physical QoL was negatively correlated with night -shift work, personal burnout, and number of body parts with discomfort. Psychological QoL was negatively correlated with night shift work and personal burnout. Environment QoL was negatively correlated with being male, night shift work and personal burnout. The results showed that the QoL among the packaging workers could be improved by reducing musculoskeletal discomfort, personal burnout and by improving work schedules. PMID- 29788222 TI - Chromatographic and Computational Studies of Molecular Lipophilicity and Drug likeness for few 2-Thioxo-1,3-Thiazolidin-4-one Derivatives and their Analogs. AB - Hydrophobicity of the eight 2-thioxo-1,3-thiazolidin-4-one derivatives was determined experimentally by thin-layer chromatography and predicted by means of commercially available programmers. RM values were determined by reversed-phase thin-layer chromatography with using acetonitrile-water, methanol-water, acetone water, propan-2-ol-water or 1,4-dioxane-water and compared with logP values calculated by using computer programs: HyperChem 8.0.10, Virtual Chemical Calculation Laboratory, ACD/LogP. The drug-likeness has been calculated using Molinspiration. All the heterocycles were found to obey Lipinski's rule of 5 for an orally active drug. PMID- 29788223 TI - OPTIMISATION OF A PAEDIATRIC CT BRAIN PROTOCOL: A FIGURE-OF-MERIT APPROACH. AB - Paediatric head computed tomography (CT) dose optimisation was carried out using three figure-of-merits (FOMs), based on tube voltage, current, noise, volumetric computed tomography dose index (CTDIvol) and contrast-to-noise ratio (CNR). FOM1: spatial resolution and total minimum contrast level (N) against CTDIvol; FOM2: noise against CTDIvol; FOM3: CNR against CTDIvol. Stage 1: Application of FOM1 and FOM2 on a Catphan without current modulation. Stage 2: CTDIvol and noise assessed on an anthropomorphic phantom with current modulation. Stage 3: All FOMs applied to Catphan images acquired with current modulation. Results indicated no single test case outperformed the current protocol (100 kVp, 200 mA) in all FOMs. Some test cases offered a reduction in dose at the cost of higher noise. The 120 kVp, 100-mA combination offered good compromise between dose and noise. Further investigation is required to determine whether this protocol could be added for procedures where higher noise is acceptable (e.g. craniosynostosis). PMID- 29788224 TI - Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease. AB - Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through a direct reduction of microbial iron intake and without affecting bacteria survival or species composition within the microbiota. Metabolomic analyses indicate that this drug reduces the intake of purine nucleosides (guanosine), increases the secretion of metabolite markers of purine catabolism (urate and hypoxanthine), and reduces the secretion of uracil (a pyrimidine nucleobase) in complex multispecies human biofilms. These findings demonstrate a new pathogenic mechanism for dysbiotic microbiota in IBD and characterize a novel mode of action for a class of mesalamine derivatives. Together, these observations pave the way towards a new therapeutic strategy for treatment of patients with IBD. PMID- 29788227 TI - Cessation and reduction in smoking behavior: impact of creating a smoke-free home on smokers. AB - The aim of this study was to assess the effect of a creating a smoke-free home (SFH) on cessation and reduction of cigarette smoking on low-income smokers. This secondary data analysis uses data from study participants who were originally recruited through 2-1-1 information and referral call centers in Atlanta (Georgia, 2013), North Carolina (2014) and the Texas Gulf Coast (2015) across three randomized controlled trials testing an intervention aimed at creating SFHs, pooling data from 941 smokers. Participants who reported adopting a SFH were more likely to report quitting smoking than those who did not adopt a SFH. This was true at 3-month follow-up and even more pronounced at 6-month follow-up and persisted when considering only those who consistently reported no smoking at 3 and 6 months. Among those who did not stop smoking, the number of cigarettes per day declined significantly more and quit attempts were more frequent for those who created a SFH compared with those who did not. Findings suggest that creating a SFH facilitates cessation, reduces cigarette consumption and increases quit attempts. Future studies should assess the long-term impact of SFHs on sustaining cessation. PMID- 29788226 TI - Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness. AB - BACKGROUND: Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K-dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD, but whether early human CKD is associated with vascular vitamin K deficiency is unknown. METHODS: We enrolled 137 adults without HF with varying degrees of renal function: normal estimated glomerular filtration rate (eGFR; >90 ml/min; n = 59), mildly reduced eGFR (stage 2 CKD: eGFR = 60-89 ml/min; n = 53) or at least moderately reduced eGFR (stage 3-5 CKD; eGFR < 60 ml/min; n = 25). Carotid-femoral pulse wave velocity (CF-PWV) was measured with carotid and femoral tonometry. Dephospho-uncarboxylated matrix gla protein (dp-ucMGP) was measured with enzyme-linked immunosorbent assay (ELISA) (VitaK; Maastricht University; The Netherlands). RESULT: Dp-ucMGP levels were progressively increased with decreasing renal function (eGFR >= 90: 247 pmol/l; eGFR 60-89: 488 pmol/l; eGFR < 60: 953 pmol/l; P < 0.0001). These differences persisted after adjustment for multiple potential confounders (eGFR >= 90: 314 pmol/l; eGFR 60-89: 414 pmol/l; eGFR < 60: 770 pmol/l; P < 0.0001). In a multivariable model adjusted for various confounders, dp-ucMGP was a significant independent predictor of CF-PWV (beta = 0.21; P = 0.019). In formal mediation analyses, dp-ucMGP mediated a significant relationship between eGFR and higher CF PWV (beta = -0.16; P = 0.005), whereas no significant dp-ucMGP-independent relationship was present (beta = -0.02; P = 0.80). CONCLUSIONS: CKD is associated with increased (inactive) dp-ucMGP, a vitamin K-dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD. PMID- 29788225 TI - LnChrom: a resource of experimentally validated lncRNA-chromatin interactions in human and mouse. AB - Long non-coding RNAs (lncRNAs) constitute an important layer of chromatin regulation that contributes to various biological processes and diseases. By interacting with chromatin, many lncRNAs can regulate that state of chromatin by recruiting chromatin-modifying complexes and thus control large-scale gene expression programs. However, the available information on interactions between lncRNAs and chromatin is hidden in a large amount of dispersed literature and has not been extensively collected. We established the LnChrom database, a manually curated resource of experimentally validated lncRNA-chromatin interactions. The current release of LnChrom includes 382 743 interactions in human and mouse. We also manually collected detailed metadata for each interaction pair, including those of chromatin modifying factors, epigenetic marks and disease associations. LnChrom provides a user-friendly interface to facilitate browsing, searching and retrieving of lncRNA-chromatin interaction data. Additionally, a large amount of multi-omics data was integrated into LnChrom to aid in characterizing the effects of lncRNA-chromatin interactions on epigenetic modifications and transcriptional expression. We believe that LnChrom is a timely and valuable resource that can greatly motivate mechanistic research into lncRNAs.Database URL: http://biocc.hrbmu.edu.cn/LnChrom/. PMID- 29788229 TI - SubtiWiki in 2018: from genes and proteins to functional network annotation of the model organism Bacillus subtilis. AB - Living cells are made up of individual parts, i.e. the genome, the proteins, the RNA and lipid molecules as well as the metabolites and ions. However, life depends on the functional interaction among these components which is often organized in networks. Here, we present the recent development of SubtiWiki, the integrated database for the model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). SubtiWiki is based on a relational database and provides access to published information about the genes and proteins of B. subtilis and about metabolic and regulatory pathways. We have included a network visualization tool that can be used to visualize regulatory as well as protein-protein interaction networks. The resulting interactive graphical presentations allow the user to detect novel associations and thus to develop novel hypotheses that can then be tested experimentally. To facilitate the mobile use of SubtiWiki, we provide enhanced versions of the SubtiWiki App that are available for iOS and Android devices. Importantly, the App allows to link private notes and pictures to the gene/protein pages that can be synchronized on multiple devices. SubtiWiki has become one of the most complete resources of knowledge on a living organism. PMID- 29788228 TI - Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development. AB - The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits. PMID- 29788230 TI - Tumor-Infiltrating Lymphocytes in Patients Receiving Trastuzumab/Pertuzumab-Based Chemotherapy: A TRYPHAENA Substudy. AB - Background: There is an urgent requirement to identify biomarkers to tailor treatment in human epidermal growth factor receptor 2 (HER2)-amplified early breast cancer treated with trastuzumab/pertuzumab-based chemotherapy. Methods: Among the 225 patients randomly assigned to trastuzumab/pertuzumab concurrently or sequentially with an anthracycline-containing regimen or concurrently with an anthracycline-free regimen in the Tryphaena trial, we determined the percentage of tumor-infiltrating lymphocytes (TILs) at baseline in 213 patients, of which 126 demonstrated a pathological complete response (pCR; ypT0/is ypN0), with 28 demonstrating event-free survival (EFS) events. We investigated associations between baseline TIL percentage and either pCR or EFS after adjusting for clinicopathological characteristics using logistic and Cox regression models, respectively. To understand TIL biology, we evaluated associations between baseline TILs and baseline tumor gene expression data (800 gene set by NanoString) in a subset of 173 patients. All statistical tests were two-sided. Results: Among the patients with measurable TILs at baseline, the median level was 14.1% (interquartile range = 7.1%-32.4%). After adjusting for clinicopathological characteristics, baseline percentage TIL was not associated with pCR (adjusted odds ratio [aOR] for every 10-percentage unit increase in TILs = 1.12, 95% confidence interval [CI] = 0.95 to 1.31, P = .17). At a median follow up of 4.7 years, for every increase in baseline TILs of 10%, there was a 25% reduction in the hazard for an EFS event (aOR = 0.75, 95% CI = 0.56 to 1.00, P = .05) after adjusting for baseline clinicopathological characteristics and pCR. Additionally, genes associated with epithelial-mesenchymal transition, angiogenesis, and T-cell inhibition such as SNAIL1, ZEB1, NOTCH3, and B7-H3 were statistically significantly inversely correlated with percentage TIL. Conclusions: Baseline TIL percentage provides independent prognostic information in patients treated with trastuzumab/pertuzumab-based neoadjuvant chemotherapy. However, further validation is required. PMID- 29788231 TI - Role of quorum sensing and chemical communication in fungal biotechnology and pathogenesis. AB - Microbial cells do not live in isolation in their environment, but rather they communicate with each other using chemical signals. This sophisticated mode of cell-to-cell signalling, known as quorum sensing, was first discovered in bacteria, and coordinates the behaviour of microbial population behaviour in a cell-density-dependent manner. More recently, these mechanisms have been described in eukaryotes, particularly in fungi, where they regulate processes such as pathogenesis, morphological differentiation, secondary metabolite production and biofilm formation. In this manuscript, we review the information available to date on these processes in yeast, dimorphic fungi and filamentous fungi. We analyse the diverse chemical 'languages' used by different groups of fungi, their possible cross-talk and interkingdom interactions with other organisms. We discuss the existence of these mechanisms in multicellular organisms, the ecophysiological role of QS in fungal colonisation and the potential applications of these mechanisms in biotechnology and pathogenesis. PMID- 29788234 TI - Prediagnostic Serum Vitamin D Levels and the Risk of Crohn's Disease and Ulcerative Colitis. PMID- 29788232 TI - Chronic Stress Exposure Reduces Parvalbumin Expression in the Rat Hippocampus through an Imbalance of Redox Mechanisms: Restorative Effect of the Antipsychotic Lurasidone. AB - Background: Psychiatric disorders are associated with altered function of inhibitory neurotransmission within the limbic system, which may be due to the vulnerability of selective neuronal subtypes to challenging environmental conditions, such as stress. In this context, parvalbumin-positive GABAergic interneurons, which are critically involved in processing complex cognitive tasks, are particularly vulnerable to stress exposure, an effect that may be the consequence of dysregulated redox mechanisms. Methods: Adult Male Wistar rats were subjected to the chronic mild stress procedure for 7 weeks. After 2 weeks, both control and stress groups were further divided into matched subgroups to receive chronic administration of vehicle or lurasidone (3 mg/kg/d) for the subsequent 5 weeks. Using real-time RT-PCR and western blot, we investigated the expression of GABAergic interneuron markers and the levels of key mediators of the oxidative balance in the dorsal and ventral hippocampus. Results: Chronic mild stress induced a specific decrease of parvalbumin expression in the dorsal hippocampus, an effect normalized by lurasidone treatment. Interestingly, the regulation of parvalbumin levels was correlated to the modulation of the antioxidant master regulator NRF2 and its chaperon protein KEAP1, which were also modulated by pharmacological intervention. Conclusions: Our findings suggest that the susceptibility of parvalbumin neurons to stress may represent a key mechanism contributing to functional and structural impairments in specific brain regions relevant for psychiatric disorders. Moreover, we provide new insights on the mechanism of action of lurasidone, demonstrating that its chronic treatment normalizes chronic mild stress-induced parvalbumin alterations, possibly by potentiating antioxidant mechanisms, which may ameliorate specific functions that are deteriorated in psychiatric patients. PMID- 29788233 TI - Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes from the European Society for Blood and Marrow Transplantation. AB - Background/Aims: Autologous haematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe, treatment-refractory Crohn's disease (CD). The evidence base for AHSCT for CD is limited, with one randomised trial (ASTIC) suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe outside the ASTIC trial. Methods: We identified 99 patients in the European Society for Blood and Marrow Transplantation (EBMT) registry who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in 7 countries. Results: Median patient age was 30 years (range 20-65). Patients had failed or been intolerant to a median of 6 lines of drug therapy. 61/82 (74%) had had surgery. Following AHSCT, 53/78 (68%) experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months (range 6 174). 22/82 (27%) required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at last follow-up, 57% (24/42) achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at one year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% CI 1.14-4.83, p=0.02). One patient died due to infectious complications (CMV disease) at day +56. Conclusions: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn's disease. Further prospective randomised controlled trials against standard of care are warranted. PMID- 29788235 TI - Heart Under Attack: Cardiac Manifestations of Inflammatory Bowel Disease. AB - There is a well-established association between chronic inflammation and an elevated risk of heart disease among patients with systemic autoimmune conditions. This review aims to summarize existing literature on the relationship between inflammatory bowel disease and ischemic heart disease, heart failure, arrhythmia, and pericarditis, with particular attention to approaches to management and treatment. PMID- 29788238 TI - Atypical bypass tracts: can they be recognized during sinus rhythm? AB - Atypical bypass tracts or variants of ventricular pre-excitation are rare anatomic structures often with rate-dependent slowing in conduction, called decremental conduction. During sinus rhythm, electrocardiographic recognition of those structures may be difficult because unlike in the Wolff-Parkinson-White syndrome where usually overt ventricular pre-excitation is present, the electrocardiogram (ECG) often shows a subtle pre-excitation pattern because of less contribution to ventricular activation over the slow and decrementally conducting bypass. Following the structure described by Ivan Mahaim and Benatt corresponding to a fasciculoventricular pathway, several other new variants of ventricular pre-excitation were reported. In this review, we aim to discuss the electrocardiographic pattern of the different subtypes of variants of ventricular pre-excitation, including the atriofascicular pathway, long and short decrementally conducting atrioventricular pathways, fasciculoventricular pathway, the atrio-Hisian bypass tract, and nodoventricular and nodofascicular fibres. Emphasis will be on the ECG findings during sinus rhythm. PMID- 29788236 TI - A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency. AB - Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology. PMID- 29788241 TI - Microsurgical Treatment of Distal Anterior Cerebral Artery Aneurysms: 3 Dimensional Operative Video. AB - Selecting appropriate patient position for surgery must take into consideration a variety of factors. For an interhemispheric approach to distal anterior cerebral artery (DACA) aneurysms, the patient may be positioned with the head either horizontal or vertical with respect to the floor. We preferentially place the patient in the supine position with the shoulder elevated and the head turned parallel to the floor with the side of the approach down and the vertex tilted 45 degrees up. In this way, gravity is utilized to allow the right frontal lobe to fall away from the falx, eliminating the need for retraction. To demonstrate the importance of individualizing the choice of position to each patient, we present here 2 illustrative cases of DACA aneurysms in which different positioning was selected. One patient presented with a 7-mm bilobed pericallosal artery aneurysm; the aneurysm was approached with the head horizontal with respect to the floor. The second patient had a 3-mm DACA aneurysm and a right frontal proliferative angiopathy and developmental venous anomaly with evidence of prior hemorrhage. Due to the vascular anomaly, we positioned the head in a vertical position for surgery to clip the aneurysm, which was thought to be the source of hemorrhage. The videos illustrate the approach to DACA aneurysms, which typically exposes the aneurysm before complete exposure of the proximal parent artery is obtained. In one case, the use of both frameless guidance and intraoperative angiography was useful in identifying a small previously ruptured aneurysm. All appropriate patient consents were obtained for this submission. Video and Figures (0:57-1:16 and 6:30-6:37), (c) 2017 Department of Neurosurgery, Emory University. Used with permission. PMID- 29788239 TI - Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis. AB - In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 MUg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 * 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 MUg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes. PMID- 29788242 TI - Challenges for family medicine research: a global perspective. PMID- 29788240 TI - Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease. AB - Background: We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods: Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results: Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn's disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohn's disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions: LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening. PMID- 29788237 TI - Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study. AB - Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases (VEO-IBD). The present study aimed at defining how next-generation sequencing (NGS) methods can be used to improve identification of known molecular diagnosis and adapt treatment. Methods: 207 children were recruited in 45 Paediatric centres through an international collaborative network (ESPGHAN GENIUS working group) with a clinical presentation of severe VEO-IBD (n=185) or an anamnesis suggestive of a monogenic disorder (n=22). Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing (WES) of parents-child trios. Genetic findings were validated clinically and/or functionally. Results: Molecular diagnosis was achieved in 66/207 children (32%): 61% with small bowel inflammation, 39% with colitis and perianal lesions and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations and identified large exonic copy number variations previously missed by WES. Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD. PMID- 29788243 TI - Social support and the intimate partner violence victimization among adults from six European countries. AB - Background: Social support may buffer the negative effects of violence on physical and mental health. Family medicine providers play an essential role in identifying the available social support and intervening in intimate partner violence (IPV). Objective: This study aimed at assessing the association between social support and the IPV victimization among adults from six European countries. Methods: This is a cross-sectional multi-centre study that included individuals from Athens (Greece), Budapest (Hungary), London (UK), Ostersund (Sweden), Porto (Portugal) and Stuttgart (Germany). Data collection was carried out between September 2010 and May 2011. The sample consisted of 3496 adults aged 18-64 years randomly selected from the general population in each city. The revised Conflict Tactics Scales was used to assess IPV victimization. Social support was assessed with the Multidimensional Scale of Perceived Social Support. Results: Participants reporting physical assault victimization experienced lower social support (mean +/- SD) than their counterparts, 66.1 +/- 13.96 versus 71.7 +/- 12.90, P < 0.001, for women; and 67.1 +/- 13.69 versus 69.5 +/- 13.52, P = 0.002 for men. Similar results were found regarding sexual coercion victimization, 69.1 +/- 14.03 versus 71.3 +/- 12.97, P = 0.005 for women and 68.0 +/- 13.29 versus 69.3 +/- 13.62, P = 0.021 for men. This study revealed lower levels of social support among participants reporting lifetime and past year victimization, independent of demographic, social and health-related factors. Conclusion: Results showed a statistically significant association between low social support and IPV victimization. Although the specific mechanisms linking social support with experiences of violence need further investigation, it seems that both informal and formal networks may be associated with lower levels of abusive situations. PMID- 29788244 TI - Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease. AB - Background: Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6 MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6 MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype. Methods: Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs). In vitro assays were performed to measure GMPS activity associated with these nsSNPs. Frequency of the nsSNPs was measured in a cohort of 530 Caucasian IBD patients. Results: Two nsSNPs in GMPS (rs747629729, rs61750370) were detected in 11 patients with very high 6-MMP:6-TGN ratios. The 2 nsSNPs were predicted to be damaging by in silico analysis. In vitro assays demonstrated that both nsSNPs resulted in a significant reduction in GMPS activity (P < 0.05). The SNP rs61750370 was significantly associated with 6-MMP:6-TGN ratios >=100 (odds ratio, 5.64; 95% confidence interval, 1.01-25.12; P < 0.031) in a subset of 264 Caucasian IBD patients. Conclusions: The GMPS SNP rs61750370 may be a reliable risk factor for extreme 6MMP preferential metabolism. PMID- 29788245 TI - Implementation science in low-resource settings: using the interactive systems framework to improve hand hygiene in a tertiary hospital in Ghana. AB - Quality issue: Low-resource clinical settings often face obstacles that challenge the implementation of recommended evidence-based practices (EBPs). Implementation science approaches are useful in identifying barriers and developing strategies to address them. Initial assessment: Ridge Regional Hospital (RRH), a tertiary referral hospital in Accra, Ghana experienced a spike in rates of neonatal sepsis and launched a quality improvement (QI) initiative that identified poor adherence to hand hygiene in the neonatal intensive care unit as a potential source of infections. Choice of solution: A multi-modal change package of World Health Organization-recommended solutions was created to address this issue. Implementation: To ensure that the outputs of the QI effort were adopted within the organization, leaders at RRH and Kybele, Inc. used an implementation science framework called the 'Interactive Systems Framework for Dissemination and Implementation' (ISF) to create a package of locally acceptable implementation strategies. The ISF has never been used before to guide implementation in low resource settings. Evaluation: Hand hygiene compliance rose from 67% to 92% overall, including a 36% increase during the night shifts-a group of healthcare workers with typically very low levels of compliance. Lessons learned: The drastic improvement in adherence to hand hygiene suggests the potential value of the joint use of QI and implementation science to promote the creation and application of contextually appropriate EBPs in low-resource settings. Our results also suggest that using an implementation framework such as the ISF could rapidly increase the uptake of other evidence-based interventions in low-resource settings. PMID- 29788247 TI - Letter to the Editor. PMID- 29788248 TI - Respiratory Tract Infections in Patients With Inflammatory Bowel Disease: Safety Analyses From Vedolizumab Clinical Trials. AB - Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates. Results: In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83-1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48-1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation. Conclusions: Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo. PMID- 29788249 TI - Nutritionally Variant Streptococci Infective Endocarditis: A Different View. PMID- 29788246 TI - Hypertension Induced Morphological and Physiological Changes in Cells of the Arterial Wall. AB - Morphological and physiological changes in the vasculature have been described in the evolution and maintenance of hypertension. Hypertension-induced vascular dysfunction may present itself as a contributing, or consequential factor, to vascular remodeling caused by chronically elevated systemic arterial blood pressure. Changes in all vessel layers, from the endothelium to the perivascular adipose tissue (PVAT), have been described. This mini-review focuses on the current knowledge of the structure and function of the vessel layers, specifically muscular arteries: intima, media, adventitia, PVAT, and the cell types harbored within each vessel layer. The contributions of each cell type to vessel homeostasis and pathophysiological development of hypertension will be highlighted. PMID- 29788251 TI - Corrigendum. PMID- 29788250 TI - Comparative Genomics Reveals Thousands of Novel Chemosensory Genes and Massive Changes in Chemoreceptor Repertories across Chelicerates. AB - Chemoreception is a widespread biological function that is essential for the survival, reproduction, and social communication of animals. Though the molecular mechanisms underlying chemoreception are relatively well known in insects, they are poorly studied in the other major arthropod lineages. Current availability of a number of chelicerate genomes constitutes a great opportunity to better characterize gene families involved in this important function in a lineage that emerged and colonized land independently of insects. At the same time, that offers new opportunities and challenges for the study of this interesting animal branch in many translational research areas. Here, we have performed a comprehensive comparative genomics study that explicitly considers the high fragmentation of available draft genomes and that for the first time included complete genome data that cover most of the chelicerate diversity. Our exhaustive searches exposed thousands of previously uncharacterized chemosensory sequences, most of them encoding members of the gustatory and ionotropic receptor families. The phylogenetic and gene turnover analyses of these sequences indicated that the whole-genome duplication events proposed for this subphylum would not explain the differences in the number of chemoreceptors observed across species. A constant and prolonged gene birth and death process, altered by episodic bursts of gene duplication yielding lineage-specific expansions, has contributed significantly to the extant chemosensory diversity in this group of animals. This study also provides valuable insights into the origin and functional diversification of other relevant chemosensory gene families different from receptors, such as odorant-binding proteins and other related molecules. PMID- 29788252 TI - Translation: The Universal Structural Core of Life. AB - The Universal Gene Set of Life (UGSL) is common to genomes of all extant organisms. The UGSL is small, consisting of <100 genes, and is dominated by genes encoding the translation system. Here we extend the search for biological universality to three dimensions. We characterize and quantitate the universality of structure of macromolecules that are common to all of life. We determine that around 90% of prokaryotic ribosomal RNA (rRNA) forms a common core, which is the structural and functional foundation of rRNAs of all cytoplasmic ribosomes. We have established a database, which we call the Sparse and Efficient Representation of the Extant Biology (the SEREB database). This database contains complete and cross-validated rRNA sequences of species chosen, as far as possible, to sparsely and efficiently sample all known phyla. Atomic-resolution structures of ribosomes provide data for structural comparison and validation of sequence-based models. We developed a similarity statistic called pairing adjusted sequence entropy, which characterizes paired nucleotides by their adherence to covariation and unpaired nucleotides by conventional conservation of identity. For canonically paired nucleotides the unit of structure is the nucleotide pair. For unpaired nucleotides, the unit of structure is the nucleotide. By quantitatively defining the common core of rRNA, we systematize the conservation and divergence of the translational system across the tree of life, and can begin to understand the unique evolutionary pressures that cause its universality. We explore the relationship between ribosomal size and diversity, geological time, and organismal complexity. PMID- 29788254 TI - Edith + Eddie. PMID- 29788253 TI - Effectiveness of a Blended Physical Therapist Intervention in People With Hip Osteoarthritis, Knee Osteoarthritis, or Both: A Cluster-Randomized Controlled Trial. AB - Background: Integrating physical therapy sessions and an online application (e Exercise) might support people with hip osteoarthritis (OA), knee OA, or both (hip/knee OA) in taking an active role in the management of their chronic condition and may reduce the number of physical therapy sessions. Objective: The objective of this study was to investigate the short- and long-term effectiveness of e-Exercise compared to usual physical therapy in people with hip/knee OA. Design: The design was a prospective, single-blind, multicenter, superiority, cluster- randomized controlled trial. Setting: The setting included 143 primary care physical therapist practices. Participants: The participants were 208 people who had hip/knee OA and were 40 to 80 years of age. Intervention: e-Exercise is a 3-month intervention in which about 5 face-to-face physical therapy sessions were integrated with an online application consisting of graded activity, exercise, and information modules. Usual physical therapy was conducted according to the Dutch physical therapy guidelines on hip and knee OA. Measurements: Primary outcomes, measured at baseline after 3 and 12 months, were physical functioning and free-living physical activity. Secondary outcome measures were pain, tiredness, quality of life, self-efficacy, and the number of physical therapy sessions. Results: The e-Exercise group (n = 109) received, on average, 5 face-to face sessions; the usual physical therapy group (n = 99) received 12. No significant differences in primary outcomes between the e-Exercise group and the usual physical therapy group were found. Within-group analyses for both groups showed a significant improvement in physical functioning. After 3 months, participants in the e-Exercise group reported an increase in physical activity; however, no objectively measured differences in physical activity were found. With respect to secondary outcomes, after 12 months, sedentary behavior significantly increased in the e-Exercise group compared with the usual physical therapy group. In both groups, there were significant improvements for pain, tiredness, quality of life, and self-efficacy. Limitations: The response rate at 12 months was 65%. Conclusions: The blended intervention, e-Exercise, was not more effective than usual physical therapy in people with hip/knee OA. PMID- 29788255 TI - Reproductive Hormones and Subclinical Cardiovascular Disease in Midlife Women. AB - Context: Reproductive hormones are important to the pathophysiology of cardiovascular disease (CVD) in women. However, standard estradiol (E2) and testosterone (T) assays lack sensitivity at the levels of postmenopausal women. Objective: Investigate relations of mass spectrometry-assessed estrone (E1), E2, and T and SHBG and subclinical CVD in women. Design, Setting, and Participants: Three hundred and four perimenopausal and postmenopausal women aged 40 to 60 years underwent subclinical CVD measurements. E1, E2, and T were assayed using liquid chromatography-tandem mass spectrometry; free T (FT) was estimated using ensemble allostery models. Regression models were adjusted for CVD risk factors. Main Outcome Measures: Carotid artery intima media thickness, interadventitial diameter (IAD), and plaque; brachial flow mediated dilation (FMD). Results: Higher E1 was related to higher FMD [beta(SE) = 0.77 (0.37), P = 0.04], indicating better endothelial function. Higher E2 was related to lower IAD [beta(SE) = -0.07 (0.02), P = 0.004], indicating less carotid remodeling. Higher SHBG was related to higher FMD [beta(SE) = 1.31 (0.40), P = 0.001], yet higher IAD [beta(SE) = 0.15 (0.06), P = 0.02] and plaque [OR (95% CI) = 1.84 (1.16 to 2.91), P = 0.009]; FT showed a similar yet inverse pattern of relations as SHBG. Thus, higher SHBG and lower FT were associated with better endothelial function, yet greater carotid remodeling and plaque. Conclusions: Endogenous E1 levels were related to endothelial function and E2 to vascular remodeling, suggesting distinct roles of these estrogens. SHBG and FT have complex roles depending on the vessel under study. PMID- 29788256 TI - Distinct HLA associations of LGI1 and CASPR2-antibody diseases. AB - The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA DRB1*07:01 was strongly represented [odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 * 10-26]. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 [odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 * 10-6]. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1 derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation. PMID- 29788258 TI - Is the plasma aldosterone-to-renin ratio associated with blood pressure response to treatment in general practice? AB - Background: Individualized antihypertensive treatment based on specific biomarkers such as renin may lead to more effective blood pressure control in patients with newly diagnosed essential hypertension. Recent studies suggested that the plasma aldosterone-to-renin ratio (ARR) may also be a candidate predictor for this purpose. Objective: To assess whether the ARR is associated with the blood pressure response to antihypertensive treatment in patients with newly diagnosed hypertension. Methods: In this prospective cohort study in primary care, we determined the ARR in patients with newly diagnosed hypertension prior to starting treatment. Treatment was categorized in five groups: no medication, use of angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker, use of calcium channel blocker, use of diuretic, or use of beta blocker. We examined the relation between the ARR and blood pressure response within 1 year of treatment, taking into account the type of antihypertensive treatment and adjusting for gender, age, baseline blood pressure, and comorbidity. Results: Out of 304 patients, we used 947 measurements (727 no medication, 220 medication) for analysis. There was no association between the ARR and the response in blood pressure, and this applied to each treatment group. Target blood pressure, defined as systolic blood pressure <140 mmHg, was reached in 31% of patients. There was no association between the ARR and reaching target blood pressure (OR 1.002, 95% CI 0.983-1.022). Conclusion: The ARR is not associated with the response in blood pressure within 1 year of antihypertensive treatment in primary care. PMID- 29788260 TI - Impact of Obesity on Short- and Intermediate-Term Outcomes in Inflammatory Bowel Diseases: Pooled Analysis of Placebo Arms of Infliximab Clinical Trials. AB - Background and aims: To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical trials of infliximab in IBD and using the Yale Open Data Access (YODA) Project. Methods: We obtained IPD from 4 placebo-controlled trials of infliximab in adults with IBD (ACCENT-I and ACCENT-II; ACT-1 and ACT-2). Patients were categorized into quartiles based on body mass index (BMI) or weight at time of trial entry. Primary outcome was clinical remission (Crohn's disease activity index [CDAI]<150, Mayo Clinic Score <3); secondary outcomes were clinical response and mucosal healing. Using multivariable logistic regression analysis, we compared association between quartiles of BMI (or weight) and achieving remission, after adjusting for sex, smoking, disease activity, and concomitant prednisone or immunomodulators. Results: We included 575 placebo-treated patients (mean age 38 years, 51.6% males, 16% obese). Obesity was not associated with odds of achieving clinical remission (Q4 vs Q1: adjusted OR, 1.36; 95% CI, 0.65-2.89; P-value for trend = 0.57), clinical response (Q4 vs Q1: adjusted OR, 1.31; 95% CI, 0.61-2.81; P = 0.45), or mucosal healing remission (Q4 vs Q1: adjusted OR, 0.55; 95% CI, 0.12-2.34; P = 0.31). These results were consistent across strata based on disease type (CD and ulcerative colitis) and trial design (induction and maintenance therapy). Conclusions: Based on IPD pooled analysis of placebo arms, obesity does not significantly impact short- and intermediate-term clinical outcomes in patients with IBD. The impact of obesity on long-term patient important outcomes like surgery and hospitalization merits evaluation. PMID- 29788257 TI - Molecular modularity and asymmetry of the molluscan mantle revealed by a gene expression atlas. AB - Background: Conchiferan molluscs construct a biocalcified shell that likely supported much of their evolutionary success. However, beyond broad proteomic and transcriptomic surveys of molluscan shells and the shell-forming mantle tissue, little is known of the spatial and ontogenetic regulation of shell fabrication. In addition, most efforts have been focused on species that deposit nacre, which is at odds with the majority of conchiferan species that fabricate shells using a crossed-lamellar microstructure, sensu lato. Results: By combining proteomic and transcriptomic sequencing with in situ hybridization we have identified a suite of gene products associated with the production of the crossed-lamellar shell in Lymnaea stagnalis. With this spatial expression data we are able to generate novel hypotheses of how the adult mantle tissue coordinates the deposition of the calcified shell. These hypotheses include functional roles for unusual and otherwise difficult-to-study proteins such as those containing repetitive low complexity domains. The spatial expression readouts of shell-forming genes also reveal cryptic patterns of asymmetry and modularity in the shell-forming cells of larvae and adult mantle tissue. Conclusions: This molecular modularity of the shell-forming mantle tissue hints at intimate associations between structure, function, and evolvability and may provide an elegant explanation for the evolutionary success of the second largest phylum among the Metazoa. PMID- 29788259 TI - Lifetime Smoking History and Risk of Lung Cancer: Results From the Framingham Heart Study. AB - Background: The relative risk of lung cancer decreases with years since quitting (YSQ) smoking, but risk beyond 25 YSQ remains unclear. Current lung cancer screening guidelines, which exclude smokers with more than 15 YSQ, may not detect lung cancers in this population. Methods: We analyzed data from Framingham Heart Study Original (n = 3905) and Offspring cohort (n = 5002) participants for lifetime smoking and lung cancer incidence from 1954 to 1958 (Exam 4) and 1971 to 1975 (Exam 1), respectively, through 2013. We used multivariable-adjusted Cox proportional hazards regression models to compare current, former, and never smokers and lung cancer risk. Smoking status and covariates were time-updated every two years (Original) or four years (Offspring). Primary analyses were restricted to heavy ever smokers with more than 21.3 pack-years; additional analyses included all ever smokers. Results: On follow-up (median = 28.7 years), 284 lung cancers were detected: incidence rates/1000 person-years in current, former, and never smokers were 1.97 (95% confidence interval [CI] = 1.66 to 2.33), 1.61 (95% CI = 1.34 to 1.93), and 0.26 (95% CI = 0.17 to 0.39), respectively. Heavy former (vs never) smokers had elevated lung cancer risk at all YSQ (<5: hazard ratio [HR] = 12.12, 95% CI = 6.94 to 21.17; 5-9: HR = 11.77, 95% CI = 6.78 to 20.45; 10-14: HR = 7.81, 95% CI = 3.98 to 15.33; 15-24: HR = 5.88, 95% CI = 3.19-10.83; >=25: HR = 3.85, 95% CI = 1.80 to 8.26). Heavy former (vs current) smokers had 39.1% lower lung cancer risk within five YSQ. Among all former smokers, 40.8% of lung cancers occurred after more than 15 YSQ. Conclusions: Among heavy former smokers, lung cancer risk drops within five YSQ relative to continuing smokers, yet it remains more than threefold higher than never smokers after 25 YSQ. Four of ten lung cancers occurred in former smokers with more 15 YSQ, beyond the screening window of the current guideline. PMID- 29788261 TI - Behavior Change Techniques Used in Digital Behavior Change Interventions to Reduce Excessive Alcohol Consumption: A Meta-regression. AB - Background: Digital behavior change interventions (DBCIs) appear to reduce alcohol consumption, but greater understanding is needed of their mechanisms of action. Purpose: To describe the behavior change techniques (BCTs) used in DBCIs and examine whether individual BCTs, the inclusion of more BCTs or more Control Theory congruent BCTs is associated with increased effectiveness. Methods: Forty one randomized control trials were extracted from a Cochrane review of alcohol reduction DBCIs and coded for up to 93 BCTs using an established and reliable method. Random effects unadjusted and adjusted meta-regression models were performed to assess associations between BCTs and intervention effectiveness. Results: Interventions used a mean of 9.1 BCTs (range 1-22), 23 different BCTs were used in four or more trials. Trials that used "Behavior substitution" ( 95.112 grams per week [gpw], 95% CI: -162.90, -27.34), "Problem solving" (-45.92 gpw, 95% CI: -90.97, -0.87) and "Credible source" (-32.09 gpw, 95% CI: -60.64, 3.55) were significantly associated with greater alcohol reduction than trials without these BCTs. The "Behavior substitution" result should be treated as preliminary because it was reported in only four trials, three of which were conducted by the same research group. "Feedback" was used in 98% of trials (n = 41); other Control Theory congruent BCTs were used less frequently: for example, "Goal setting" 43% (n = 18) and "Self-monitoring" 29%, (n = 12). Conclusions: "Behavior substitution," "Problem solving," and "Credible source" were associated with greater alcohol reduction. Many BCTs were used infrequently in DBCIs, including BCTs with evidence of effectiveness in other domains, such as "Self monitoring" and "Goal setting." PMID- 29788262 TI - 6-Thioguanine Nucleotide Levels Are Associated With Mucosal Healing in Patients With Crohn's Disease. AB - Background: Level of 6-thioguanine nucleotides (6-TGN) has been reported to be associated with clinical remission in patients with Crohn's disease (CD) receiving maintenance treatment with thiopurines. Whether 6-TGN levels are associated with mucosal healing (MH) has seldom been investigated. We aimed to assess the correlation between 6-TGN levels and MH in patients with CD. Methods: This was a retrospective, cross-sectional, observational, multicenter study of 119 patients with CD treated with thiopurines in 3 inflammatory bowel disease referral centers (France, Australia, and China) between June 2012 and April 2016. Established CD patients who underwent ileocolonoscopy during thiopurine treatment were included. MH was defined as simple endoscopic score-CD <3. Univariate and multivariable regression analyses were used to evaluate variables associated with MH. Results: The mean concentration of 6-TGN in the MH group was higher compared with that in the non-MH group (359.0 +/- 226.7 pmol/8 * 108 red blood cell count [RBC] vs 277.1 +/- 170.5 pmol/8 * 108 RBC; P = 0.017). The cutoff 6-TGN concentration of 397.3 pmol/8 * 108 RBC was 86.7% specific to MH, with a sensitivity of 35.3% and area under curve (AUC) of 0.631 (P = 0.010). On multivariable analysis, 6-TGN levels were associated with MH (odds ratio [OR], 3.287; 95% confidence interval [CI], 1.348-8.017; P = 0.009) whereas late initiation of AZA (longer duration from disease onset) was inversely associated with MH (OR, 0.972; 95% CI, 0.954-0.991; P = 0.004). Conclusions: Higher 6-TGN levels are independently associated with a reduced rate of endoscopically active disease and a higher rate of mucosal healing in CD patients. Prospective studies of adequate sample size are required to confirm these findings. PMID- 29788263 TI - Temporal course of vascular healing and neoatherosclerosis after implantation of durable- or biodegradable-polymer drug-eluting stents. AB - Aims: Delayed healing and endothelial dysfunction may occur with drug-eluting stents (DES), promoting accelerated infiltration of lipids in the neointima and development of neoatherosclerosis (NA). Pathology data suggest durable polymer (DP) of DES to play a major role in this process. Whether biodegradable polymer (BP) may address these issues is uncertain. We compared in vivo vessel healing and NA of current generation BP- or DP-DES using serial optical coherence tomography (OCT) assessments. Methods and results: Ninety patients with multivessel coronary artery disease were randomized 1:1 to BP everolimus-eluting stents (EES, Synergy) or DP zotarolimus-eluting stents (ZES, Resolute Integrity). Co-primary endpoints were the maximum length of uncovered struts at 3 months (powered for non-inferiority) and the percentage of patients presenting with frames of NA at 18 months (powered for superiority) as measured by OCT. The maximum length of uncovered struts at 3 months was 10 +/- 8 mm in the BP-EES group and 11 +/- 7 mm in the DP-ZES group (mean difference -1 mm; upper 97.5% confidence interval +2 mm; P = 0.05 for non-inferiority; P = 0.45 for superiority). The percentage of patients presenting with frames of NA at 18 months was low and similar between BP-EES and DP-ZES groups (11.6% vs. 15.9%; P = 0.56). There was no stent thrombosis in both groups at 24 months. Conclusion: BP EES and DP-ZES showed a similar healing response at 3 months and a low incidence of NA at 18 months. Biocompatible polymers, regardless of whether they are durable or biodegradable, may favourably impact the long-term vascular response to current-generation DES. PMID- 29788265 TI - Gene Expression Profile in Frontal Cortex in Sporadic Frontotemporal Lobar Degeneration-TDP. AB - Molecular alterations compromising key metabolic pathways are poorly understood in sporadic frontotemporal lobar degeneration with TDP-43 pathology (sFTLD-TDP). Whole-transcriptome array, RT-qPCR validation, gel electrophoresis, and Western blotting, and mitochondrial electron transport chain (ETC) activity were comparatively examined in frontal cortex (area 8) of 16 sFTLD-TDP cases and 14 controls. Assessment of 111 genes by RT-qPCR showed deregulation of 81 genes linked to neurotransmission and synapses, neuronal architecture, cytoskeleton of axons and dendrites, vesicle trafficking, purines, mitochondria, and energy metabolism in sFTLD-TDP. Western blotting studies disclosed downregulation of several mitochondrial subunits encoded by genomic DNA and MT-CO1 encoded by the mitochondrial DNA. Mitochondrial ETC activity of complexes I, IV, and V was decreased in sFTLD-TDP. These findings provide robust information about downregulation of genes involved in vital biochemical pathways and in synaptic neurotransmission which may help to increase understanding about the biochemical substrates of clinical manifestations in sFTLD-TDP. PMID- 29788264 TI - MPK-1/ERK pathway regulates DNA damage response during development through DAF 16/FOXO. AB - Ultraviolet (UV) induces distorting lesions to the DNA that can lead to stalling of the RNA polymerase II (RNAP II) and that are removed by transcription-coupled nucleotide excision repair (TC-NER). In humans, mutations in the TC-NER genes CSA and CSB lead to severe postnatal developmental defects in Cockayne syndrome patients. In Caenorhabditis elegans, mutations in the TC-NER genes csa-1 and csb 1, lead to developmental growth arrest upon UV treatment. We conducted a genetic suppressor screen in the nematode to identify mutations that could suppress the developmental defects in csb-1 mutants. We found that mutations in the ERK1/2 MAP kinase mpk-1 alleviate the developmental retardation in TC-NER mutants, while constitutive activation of the RAS-MAPK pathway exacerbates the DNA damage induced growth arrest. We show that MPK-1 act via insulin/insulin-like signaling pathway and regulates the FOXO transcription factor DAF-16 to mediate the developmental DNA damage response. PMID- 29788266 TI - Dietary Magnesium Alleviates Experimental Murine Colitis Through Upregulation of the Transient Receptor Potential Melastatin 6 Channel. AB - Background: Magnesium (Mg) is essential for human health and is absorbed mainly in the intestine. In view of the likely occurrence of an Mg deficit in inflammatory bowel disease (IBD) and the documented role of Mg in modulating inflammation, the present study addresses whether Mg availability can affect the onset and progression of intestinal inflammation. Methods: To study the correlation between Mg status and disease activity, we measured magnesemia by atomic absorption spectroscopy in a cohort of IBD patients. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, fecal occult blood, diarrhea, colon length, and histology. Expression of the transient receptor potential melastatin (TRPM) 6 channel was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry in murine colon tissues. The effect of Mg on epithelial barrier formation/repair was evaluated in human colon cell lines. Results: Inflammatory bowel disease patients presented with a substantial Mg deficit, and serum Mg levels were inversely correlated with disease activity. In mice, an Mg-deficient diet caused hypomagnesemia and aggravated DSS-induced colitis. Colitis severely compromised intestinal Mg2+ absorption due to mucosal damage and reduction in TRPM6 expression, but Mg supplementation resulted in better restoration of mucosal integrity and channel expression. Conclusions: Our results highlight the importance of evaluating and correcting magnesemia in IBD patients. The murine model suggests that Mg supplementation may represent a safe and cost-effective strategy to reduce inflammation and restore normal mucosal function. PMID- 29788268 TI - Serosurvey of West Nile virus in household-reared pigeons in Bauchi metropolis, Nigeria. AB - Background: In Nigeria not much is known about West Nile virus (WNV) in pigeons. This study determined the involvement of household-reared pigeons in the circulation of WNV in Nigeria. Methods: It was a cross-sectional study. Serological detection was done using competitive enzyme-linked immunosorbent assay and a pretested interviewer-administered questionnaire was used to collect information on risk factors related to WNV in households. Results: From the156 households enumerated, 376 pigeon serum samples were collected and tested for antibodies. A total of 3.5% (13/376) of the pigeon sera were positive. Risk factors for WNV in households indicated that not having a blocked or stagnant gutter that is not flowing, and having mosquito nets at the windows and doors were found to be protective (OR=0.69, 95% CI, 0.21-2.29; OR=0.46, 95% CI, 0.14 1.56). Conclusions: Household-reared pigeons contribute to the epidemiology of WNV. There is need for further studies in other species of birds, and education of the populace about its zoonotic transmission. PMID- 29788269 TI - Smoking and the Risk of Pouchitis in Ulcerative Colitis Patients With Ileal Pouch Anal Anastomosis. AB - Background: Ulcerative colitis (UC) patients who undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA) may develop pouchitis, a poorly understood inflammatory condition. There is controversy over whether tobacco use can protect against pouchitis. We undertook this investigation to further evaluate whether smoking reduces the risk of developing pouchitis and to determine whether other previously associated clinical factors change the risk for pouchitis. Methods: We performed a retrospective analysis using a consented inflammatory bowel disease (IBD) natural history registry between the years 1995-2015 from a single tertiary care referral center. Demographic data, medical history, surgical information, medication use, laboratory data, and smoking history were abstracted. Former smokers had quit for at least 1 year. The primary end point was development of pouchitis. Results: Of the 353 UC patients with IPAA in this study, 126 (35.6%) developed pouchitis. Prior tobacco use (P < 0.0001) was more common in patients who developed pouchitis. Former and active smokers were more likely to develop pouchitis compared with those without a history of tobacco use (63.4% vs 27.3% respectively, P < 0.001). There was no significant difference in active smoking rate between those without pouchitis and the group that did develop pouchitis. Multivariate analysis demonstrated that the only independent risk factor associated with pouchitis was a history of tobacco use. Conclusions: These results suggest that smoking cessation may increase the likelihood of developing pouchitis in tobacco users with UC and IPAA, but active smoking does not seem to be more effective in preventing this condition. PMID- 29788271 TI - The Innate Immune System in the Gastrointestinal Tract: Role of Intraepithelial Lymphocytes and Lamina Propria Innate Lymphoid Cells in Intestinal Inflammation. AB - Background: The gastrointestinal tract harbors the largest microbiota load in the human body, hence maintaining a delicate balance between immunity against invading pathogens and tolerance toward commensal. Such immune equilibrium, or intestinal homeostasis, is conducted by a tight regulation and cooperation of the different branches of the immune system, including the innate and the adaptive immune system. However, several factors affect this delicate equilibrium, ultimately leading to gastrointestinal disorders including inflammatory bowel disease. Therefore, here we decided to review the currently available information about innate immunity lymphocyte subsets playing a role in intestinal inflammation. Results: Intestinal innate lymphocytes are composed of intraepithelial lymphocytes (IELs) and lamina propria innate lymphoid cells (ILCs). While IELs can be divided into natural or induced, ILCs can be classified into type 1, 2, or 3, resembling, respectively, the properties of TH1, TH2, or TH17 adaptive lymphocytes. Noteworthy, the phenotype and function of both IELs and ILCs are disrupted under inflammatory conditions, where they help to exacerbate intestinal immune responses. Conclusions: The modulation of both IELs and ILCs to control intestinal inflammatory responses represents a major challenge, as they provide tight regulation among the epithelium, the microbiota, and the adaptive immune system. An improved understanding of the innate immunity mechanisms involved in gastrointestinal inflammation would therefore aid in the diagnosis and further treatment of gastrointestinal inflammatory disorders. PMID- 29788272 TI - Therapeutic Drug Monitoring With Ustekinumab and Vedolizumab in Inflammatory Bowel Disease. AB - In patients with Crohn's disease (CD) and ulcerative colitis (UC), the use of therapeutic drug monitoring (TDM) with TNF-alpha antagonists has led to a personalized approach to optimize treatment and has been shown to be cost effective. The utility of this TDM-based personalized approach for novel biologic agents, which target different inflammatory pathways, is unclear. Commercial assays for ustekinumab (UST) and vedolizumab (VDZ) are available, but there is little available guidance for clinicians regarding the use of TDM with these drugs. Although there is limited evidence for definitive threshold concentrations for UST and VDZ, this review highlights the available literature on the pharmacokinetics of these medications, the association of clinical and endoscopic outcomes with drug concentrations, and the clinical utility of TDM to guide treatment decisions. PMID- 29788270 TI - Determinants of Hearing Aid Use Among Older Americans With Hearing Loss. AB - Background and Objectives: Hearing loss (HL) is common among older adults and is associated with significant psychosocial, cognitive, and physical sequelae. Hearing aids (HA) can help, but not all individuals with HL use them. This study examines how social determinants may impact HA use. Research Design and Methods: We conducted an explanatory sequential mixed methods study involving a secondary analysis of a nationally representative data set, the Health and Retirement Study (HRS; n = 35,572). This was followed up with 1:1 qualitative interviews (n = 21) with community participants to clarify our findings. Both samples included individuals aged 55 and older with a self-reported HL, with or without HA. The main outcome measure was the proportion of participants with a self-reported HL who use HA. Results and Discussion: Analysis of HRS data indicated that younger, nonwhite, non-Hispanic, lower income, and less-educated individuals were significantly less likely to use HA than their referent groups (all p values < .001). Area of residence (e.g., urban) were not significantly associated with HA use. Qualitative findings revealed barriers to HA included cost, stigma, vanity, and a general low priority placed on addressing HL by health care providers. Facilitators to obtaining and using HA included family/friend support, knowledge, and adequate insurance coverage for HA. Implications: Many socioeconomic factors hinder individuals' ability to obtain and use HA, but these obstacles appeared to be mitigated in part when insurance plans provided adequate HA coverage, or when their family/friends provided encouragement to use HA. PMID- 29788267 TI - Ribosomal protein L14 contributes to the early assembly of 60S ribosomal subunits in Saccharomyces cerevisiae. AB - The contribution of most ribosomal proteins to ribosome synthesis has been quite well analysed in Saccharomyces cerevisiae. However, few yeast ribosomal proteins still await characterization. Herein, we show that L14, an essential 60S ribosomal protein, assembles in the nucleolus at an early stage into pre-60S particles. Depletion of L14 results in a deficit in 60S subunits and defective processing of 27SA2 and 27SA3 to 27SB pre-rRNAs. As a result, 27S pre-rRNAs are subjected to turnover and export of pre-60S particles is blocked. These phenotypes likely appear as the direct consequence of the reduced pre-60S particle association not only of L14 upon its depletion but also of a set of neighboring ribosomal proteins located at the solvent interface of 60S subunits and the adjacent region surrounding the polypeptide exit tunnel. These pre-60S intermediates also lack some essential trans-acting factors required for 27SB pre rRNA processing but accumulate practically all factors required for processing of 27SA3 pre-rRNA. We have also analysed the functional interaction between the eukaryote-specific carboxy-terminal extensions of the neighboring L14 and L16 proteins. Our results indicate that removal of the most distal parts of these extensions cause slight translation alterations in mature 60S subunits. PMID- 29788273 TI - The patient safety culture: a systematic review by characteristics of Hospital Survey on Patient Safety Culture dimensions. AB - Purpose: To learn the weaknesses and strengths of safety culture as expressed by the dimensions measured by the Hospital Survey on Patient Safety Culture (HSOPSC) at hospitals in the various cultural contexts. The aim of this study was to identify studies that have used the HSOPSC to collect data on safety culture at hospitals; to survey their findings in the safety culture dimensions and possible contributions to improving the quality and safety of hospital care. Data sources: Medline (via PubMed), Web of Science and Scopus were searched from 2005 to July 2016 in English, Portuguese and Spanish. Study selection: Studies were identified using specific search terms and inclusion criteria. A total of 33 articles, reporting on 21 countries, was included. Data extraction: Scores were extracted by patient safety culture dimensions assessed by the HSOPSC. The quality of the studies was evaluated by the STROBE Statement. Results: The dimensions that proved strongest were 'Teamwork within units' and 'Organisational learning continuous improvement'. Particularly weak dimensions were 'Non-punitive response to error', 'Staffing', 'Handoffs and transitions' and 'Teamwork across units'. Conclusion: The studies revealed a predominance of hospital organisational cultures that were underdeveloped or weak as regards patient safety. For them to be effective, safety culture evaluation should be tied to strategies designed to develop safety culture hospital-wide. PMID- 29788276 TI - Proteomic analysis and prediction of amino acid variations that influence protein posttranslational modifications. AB - Accumulative studies have indicated that amino acid variations through changing the type of residues of the target sites or key flanking residues could directly or indirectly influence protein posttranslational modifications (PTMs) and bring about a detrimental effect on protein function. Computational mutation analysis can greatly narrow down the efforts on experimental work. To increase the utilization of current computational resources, we first provide an overview of computational prediction of amino acid variations that influence protein PTMs and their functional analysis. We also discuss the challenges that are faced while developing novel in silico approaches in the future. The development of better methods for mutation analysis-related protein PTMs will help to facilitate the development of personalized precision medicine. PMID- 29788275 TI - Feasibility and effectiveness of laparoscopic transgastric stapler-assisted circumferential esophageal mucosectomy and simultaneous fundoplication in a pig model. AB - Laparoscopic transgastric stapler-assisted mucosectomy (SAM) has been described for minimally invasive circumferential en bloc resection of Barrett's esophagus (BE). Conceivably long-term disease control might be achieved by adding antireflux surgery after resection of BE by SAM. The aim of this study was to assess the feasibility of combined SAM and fundoplication in one laparoscopic procedure in six pigs. Furthermore, the competence of the gastroesophageal junction (GEJ) was assessed at baseline, after SAM, and after subsequent laparoscopic fundoplication. At each measuring point reflux measurements were repeated 6 times in each pig. Blue-colored water was infused into the stomach to provoke reflux. Intragastric yield pressure and volume were recorded until drainage of blue solution (DBS) was noted. Time to reflux was measured by DBS and by multichannel intraluminal impedance (MII). In all animals SAM followed by laparoscopic fundoplication was feasible in a single session. A weakening of the GEJ was found after SAM, indicated by decreased yield pressure (11.5 mmHg vs. 8.5 mmHg; P < 0.001), time to DBS (90 seconds vs. 60 seconds; P = 0.008) and MII (80 seconds vs. 33 seconds; P < 0.001). After additional Nissen fundoplication the GEJ competence was restored, with measurements returning to baseline values (time to DBS 99 seconds; P = 0.15; MII 76 seconds; P = 0.84). The yield pressure increased from 11.5 mmHg at baseline to 19.7 mmHg after SAM and fundoplication (P < 0.001). Laparoscopic fundoplication and SAM may be combined in a single laparoscopic session. Although the GEJ was weakened after SAM, Nissen fundoplication restored the GEJ as an effective reflux barrier in this experiment. For clinical validation, the results need to be confirmed in a prospective human trial. PMID- 29788274 TI - Arabidopsis SKP1-like protein13 (ASK13) positively regulates seed germination and seedling growth under abiotic stress. AB - SKP1 (S-phase kinase-associated protein1) proteins are key members of the SCF (SKP-cullin-F-box protein) E3 ligase complexes that ubiquitinate target proteins and play diverse roles in plant biology. However, in comparison with other members of the SCF complex, knowledge of SKP1-like proteins is very limited in plants. In the present work, we report that Arabidopsis SKP1-like protein13 (ASK13) is differentially regulated in different organs during seed development and germination and is up-regulated in response to abiotic stress. Yeast two hybrid library screening and subsequent assessment of in vivo interactions through bimolecular fluorescence complementation analysis revealed that ASK13 not only interacts with F-box proteins but also with other proteins that are not components of SCF complexes. Biochemical analysis demonstrated that ASK13 not only exists as a monomer but also as a homo-oligomer or heteromer with other ASK proteins. Functional analysis using ASK13 overexpression and knockdown lines showed that ASK13 positively influences seed germination and seedling growth, particularly under abiotic stress. Taken together, our data strongly suggest that apart from participation to form SCF complexes, ASK13 interacts with several other proteins and is implicated in different cellular processes distinct from protein degradation. PMID- 29788277 TI - Work-related ill-health in radiographers. AB - Background: In the UK in 2015/16, 1.3 million workers self-reported a work related illness (WRI) of which an estimated 41% were due to musculoskeletal disorders (incidence rate 550 cases per 100000 people) and 37% were related to stress, anxiety and depression. Little is known about the incidence of WRIs in radiographers. Aims: To analyse the medically reported incidence of WRIs among radiographers in the UK between 1989 and 2015. Methods: Incident cases reported by physicians to The Health and Occupation Research (THOR) network through its specialist schemes from 1989 to 2015 were analysed, using the Labour Force Survey as denominator where appropriate. Results: In total, 218 cases (966 estimated cases) were reported. Of these 190 were in women. The mean age was 40.2 (20-91 years) SD +/- 11.8 years. Most cases were reported to the Occupational Physicians Reporting Activity (OPRA) scheme (n = 92). A skin diagnosis was the most frequently reported (n = 77), followed by musculoskeletal (n = 60). Within the EPIDERM scheme, radiographers had the highest incidence rate when compared to all other occupations. Conclusions: Radiographers had a higher incidence of WRI compared to all other occupations. The most frequently reported WRI was skin conditions. The observed increase in incidence is likely to be due to the increase in the number of radiographers over that time period, although there was no evidence that WRI within radiographers are declining. PMID- 29788278 TI - Prognostic value of left ventricular reverse remodelling and recurrent mitral regurgitation after personalized surgical treatment of patients with non ischaemic cardiomyopathy and functional mitral regurgitation. AB - OBJECTIVES: The aim of this study was to determine the prevalence of left ventricular reverse remodelling (LVRR) and recurrent mitral regurgitation (MR) at mid-term follow-up (1-2 years after surgery) in patients after personalized surgical treatment of heart failure and functional MR due to non-ischaemic cardiomyopathy and to assess their prognostic impact on long-term clinical outcomes. METHODS: Consecutive patients with refractory heart failure and non ischaemic MR, who underwent mitral valve surgery with or without additional procedures, were identified. Patients with complete preoperative and mid-term echocardiographic data were included. LVRR (>=15% decrease in indexed left ventricular end-systolic volume) and recurrent MR (>= Grade 2) were echocardiographically assessed at mid-term follow-up, and the primary end point was a composite of all-cause mortality and heart transplantation (HTx-free survival). RESULTS: The prevalence of LVRR was 38%, and the prevalence of recurrent MR was 20% at mid-term follow-up. The absence of LVRR and the presence of recurrent MR-which were highly correlated-were significantly associated with worse HTx-free survival. HTx-free survival 1 and 3 years after mid-term follow-up were 100% and 88 +/- 6% in patients with LVRR (n = 29), 82 +/- 7% and 68 +/- 8% in patients without LVRR and without recurrent MR (n = 34), and 49 +/- 14% and 33 +/- 13% in patients without LVRR and with recurrent MR (n = 14). CONCLUSIONS: Patients with LVRR at mid-term follow-up showed favourable HTx-free survival, whereas HTx-free survival was significantly worse in patients without LVRR and without recurrent MR and extremely poor in patients without LVRR and with recurrent MR. Close echocardiographic monitoring is warranted for timely identification of this latter subgroup of patients, in order to re-evaluate additional treatment options and improve their prognosis. PMID- 29788281 TI - A Method for Cranial Nerve XI Silencing During Surgery of the Foramen Magnum Region: Technical Case Report. AB - BACKGROUND AND IMPORTANCE: Skull base surgery involves the microdissection and intraoperative monitoring of cranial nerves, including cranial nerve XI (CN XI). Manipulation of CN XI can evoke brisk trapezius contraction, which in turn may disturb the surgical procedure and risk patient safety. Here we describe a method for temporarily silencing CN XI via direct intraoperative application of 1% lidocaine. CLINICAL PRESENTATION: A 41-yr-old woman presented with symptoms of elevated intracranial pressure and obstructive hydrocephalus secondary to a hemangioblastoma of the right cerebellar tonsil. A far-lateral suboccipital craniotomy was performed for resection of the lesion. During the initial stages of microdissection, vigorous trapezius contraction compromised the course of the operation. Following exposure of the cranial and cervical portions of CN XI, lidocaine was applied to the course of the exposed nerve. Within 3 min, trapezius electromyography demonstrated neuromuscular silencing, and further manipulation of CN XI did not cause shoulder movements. Approximately 30 min after lidocaine application, trapezius contractions returned, and lidocaine was again applied to re-silence CN XI. Gross total resection of the hemangioblastoma was performed during periods of CN XI inactivation, when trapezius contractions were absent. CONCLUSION: Direct application of lidocaine to CN XI temporarily silenced neuromuscular activity and prevented unwanted trapezius contraction during skull base microsurgery. This method improved operative safety and efficiency by significantly reducing patient movement due to the unavoidable manipulation of CN XI. PMID- 29788282 TI - The pericardial tunnel technique might produce optimal morphological repair of the scimitar syndrome. PMID- 29788279 TI - Well-Annotated microRNAomes Do Not Evidence Pervasive miRNA Loss. AB - microRNAs are conserved noncoding regulatory factors implicated in diverse physiological and developmental processes in multicellular organisms, as causal macroevolutionary agents and for phylogeny inference. However, the conservation and phylogenetic utility of microRNAs has been questioned on evidence of pervasive loss. Here, we show that apparent widespread losses are, largely, an artefact of poorly sampled and annotated microRNAomes. Using a curated data set of animal microRNAomes, we reject the view that miRNA families are never lost, but they are rarely lost (92% are never lost). A small number of families account for a majority of losses (1.7% of families account for >45% losses), and losses are associated with lineages exhibiting phenotypic simplification. Phylogenetic analyses based on the presence/absence of microRNA families among animal lineages, and based on microRNA sequences among Osteichthyes, demonstrate the power of these small data sets in phylogenetic inference. Perceptions of widespread evolutionary loss of microRNA families are due to the uncritical use of public archives corrupted by spurious microRNA annotations, and failure to discriminate false absences that occur because of incomplete microRNAome annotation. PMID- 29788283 TI - Criteria for assessing the quality of mHealth apps: a systematic review. AB - Objective: Review the existing studies including an assessment tool/method to assess the quality of mHealth apps; extract their criteria; and provide a classification of the collected criteria. Methods: In accordance with the PRISMA statement, a literature search was conducted in MEDLINE, EMBase, ISI and Scopus for English language citations published from January 1, 2008 to December 22, 2016 for studies including tools or methods for quality assessment of mHealth apps. Two researchers screened the titles and abstracts of all retrieved citations against the inclusion and exclusion criteria. The full text of relevant papers was then individually examined by the same researchers. A senior researcher resolved eventual disagreements and confirmed the relevance of all included papers. The authors, date of publication, subject fields of target mHealth apps, development method, and assessment criteria were extracted from each paper. The extracted assessment criteria were then reviewed, compared, and classified by an expert panel of two medical informatics specialists and two health information management specialists. Results: Twenty-three papers were included in the review. Thirty-eight main classes of assessment criteria were identified. These were reorganized by expert panel into 7 main classes (Design, Information/Content, Usability, Functionality, Ethical Issues, Security and Privacy, and User-perceived value) with 37 sub-classes of criteria. Conclusions: There is a wide heterogeneity in assessment criteria for mHealth apps. It is necessary to define the exact meanings and degree of distinctness of each criterion. This will help to improve the existing tools and may lead to achieve a better comprehensive mHealth app assessment tool. PMID- 29788284 TI - Military Service and Decision Quality in the Management of Knee Osteoarthritis. AB - Background: Decision quality measures the degree to which care decisions are knowledge-based and value-aligned. Because military service emphasizes hierarchy, command, and mandates some healthcare decisions, military service may attenuate patient autonomy in healthcare decisions and lower decision quality. VA is the nation's largest provider of orthopedic care. We compared decision quality in a sample of VA and non-VA patients seeking care for knee osteoarthritis. Methods: Our study sample consisted of patients newly referred to our orthopedic clinic for the management of knee osteoarthritis. None of the study patients were exposed to a knee osteoarthritis decision aid. Consenting patients were administered the Hip/Knee Decision Quality Instrument (HK-DQI). In addition, they were surveyed about decision-making preferences and demographics. We compared results to a non-VA cohort from our academic institution's arthroplasty database. Results: The HK-DQI Knowledge Score was lower in the VA cohort (45%, SD = 22, n = 25) compared with the non-VA cohort (53%, SD = 21, n = 177) (p = 0.04). The Concordance Score was lower in the VA cohort (36%, SD = 49%) compared with the control cohort (70%, SD 46%) (p = 0.003). Non-VA patients were more likely to make a high-quality decision (p = 0.05). Non-VA patients were more likely to favor a shared decision-making process (p = 0.002). Conclusions: Decision quality is lower in Veterans with knee osteoarthritis compared with civilians, placing them at risk for lower treatment satisfaction and possibly unwarranted surgical utilization. Our future work will examine if this difference is from conditioned military service behaviors or confounding demographic factors, and if conventional shared decision-making techniques will correct this deficiency. PMID- 29788285 TI - Altered Asparagine and Glutamate Homeostasis Precede Coronary Artery Disease and Type 2 Diabetes. AB - Context: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for coronary artery disease (CAD), but the overlapping metabolic disturbances preceding both diseases are insufficiently described. Objective: We hypothesized that alterations in metabolism occur years before clinical manifestation of T2DM and CAD and that these alterations are reflected in the plasma metabolome. We thus aimed to identify plasma metabolites that predict future T2DM and CAD. Design: Through use of targeted liquid chromatography-mass spectrometry, 35 plasma metabolites (amino acid metabolites and acylcarnitines) were quantified in 1049 individuals without CAD and diabetes, drawn from a population sample of 5386 in the Malmo Preventive Project (mean age, 69.5 years; 31% women). The sample included 204 individuals who developed T2DM, 384 who developed CAD, and 496 who remained T2DM and CAD free during a mean follow-up of 6.1 years. Results: In total, 16 metabolites were significantly associated with risk for developing T2DM according to logistic regression models. Glutamate (OR, 1.96; P = 5.4e-12) was the most strongly associated metabolite, followed by increased levels of branched chain amino acids. Incident CAD was predicted by three metabolites: glutamate (OR, 1.28; P = 6.6e-4), histidine (OR, 0.76; P = 5.1e-4), and asparagine (OR, 0.80; P = 2.2e-3). Glutamate (OR, 1.48; P = 1.6e-8) and asparagine (OR, 0.75; P = 1.8e-5) were both associated with a composite endpoint of developing T2DM or CAD. Conclusion: Several plasma metabolites were associated with incidence of T2DM and CAD; elevated glutamate and reduced asparagine levels were associated with both diseases. We thus discovered associations that might help shed additional light on why T2DM and CAD commonly co-occur. PMID- 29788280 TI - Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts. AB - Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time. PMID- 29788286 TI - Extracorporeal life support for primary graft dysfunction after heart transplantation. AB - OBJECTIVES: Survival after heart transplantation is steadily improving but primary graft dysfunction (PGD) is still a leading cause of death. Medical management seems useful in mild or moderate PGD, whereas extracorporeal life support (ECLS) could be suggested for severe PGD refractory to conventional treatment. Our aim is to present the results of ECLS for PGD after heart transplantation at a single-centre experience. METHODS: We performed an observational analysis of our local database. According to the International Society for Heart and Lung Transplantation classification, patients were divided into a left and biventricular failure (PGD-LV) or isolated right ventricular failure (PGD-RV) group. The primary end point was survival to hospital discharge. RESULTS: Between January 2010 and December 2016, 38 patients presented with PGD (PGD-LV n = 22, 58%; PGD-RV n = 16, 42%) requiring ECLS support. The mean age was 50.8 +/- 12.4 years and 79% were males. Baseline characteristics were comparable between the 2 groups. PGD-LV patients displayed a significantly higher mortality rate on ECLS support as opposed to PGD-RV patients (46% vs 13%, P = 0.033). The rate of complications during ECLS support was comparable between the 2 groups. Twenty-three (61%) patients were successfully weaned from ECLS (PGD-LV = 50% vs PGD-RV = 75%, P = 0.111) after a mean support of 9.0 +/- 6.4 days. Seventeen (45%) patients survived to hospital discharge (PGD-LV = 41% vs PGD-RV = 50%, P = 0.410). CONCLUSIONS: In case of severe PGD with various manifestations of ventricular failure refractory to conventional treatment, ECLS can be considered as a feasible option with satisfactory survival in this critically ill population. PMID- 29788287 TI - Provider and patient satisfaction with the integration of ambulatory and hospital EHR systems. AB - Objective: The installation of EHR systems can disrupt operations at clinical practice sites, but also lead to improvements in information availability. We examined how the installation of an ambulatory EHR at OB/GYN practices and its subsequent interface with an inpatient perinatal EHR affected providers' satisfaction with the transmission of clinical information and patients' ratings of their care experience. Methods: We collected data on provider satisfaction through 4 survey rounds during the phased implementation of the EHR. Data on patient satisfaction were drawn from Press Ganey surveys issued by the healthcare network through a standard process. Using multivariable models, we determined how provider satisfaction with information transmission and patient satisfaction with their care experience changed as the EHR system allowed greater information flow between OB/GYN practices and the hospital. Results: Outpatient OB/GYN providers became more satisfied with their access to information from the inpatient perinatal triage unit once system capabilities included automatic data flow from triage back to the OB/GYN offices. Yet physicians were generally less satisfied with how the EHR affected their work processes than other clinical and non clinical staff. Patient satisfaction dropped after initial EHR installation, and we find no evidence of increased satisfaction linked to system integration. Conclusions: Dissatisfaction of providers with an EHR system and difficulties incorporating EHR technology into patient care may negatively impact patient satisfaction. Care must be taken during EHR implementations to maintain good communication with patients while satisfying documentation requirements. PMID- 29788288 TI - Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study. AB - Background: Most patients with ulcerative colitis (UC) rely predominantly on medication for disease control. Diet interventions can reduce pharmaceutical expenditures and prolong remission. We designed a prospective study to evaluate whether an immunoglobulin G (IgG)-guided exclusion diet would improve symptoms and quality of life (QoL) in patients with UC. Methods: The 6-month diet intervention included 97 patients with UC, who were randomly divided into an intervention group (n = 49) and a control (n = 48) group. Individual diet plans were created for the intervention group according to IgG titers; the control group ate a healthy diet as normal. Observational indices included disease activity, extraintestinal manifestations, nutritional status, and QoL. Relationships between food-specific IgG antibodies and these indices were also analyzed. Results: At baseline, there were no significant differences between the groups. Food-specific IgG antibodies were detected in 70.10% of participants. After intervention, the Mayo score was significantly lower in the intervention group than in the control group (2.41 +/- 0.89 vs 3.52 +/- 1.15, P < 0.05). The number of patients with extraintestinal manifestations decreased from 7 to 2 in the intervention group and from 6 to 5 in the control group. As for nutritive indices, the intervention group had higher mean body mass index and albumin than the control group (23.88 +/- 3.31 vs 21.50 +/- 6.24 kg/m2, respectively, P < 0.05; 48.05 +/- 6.39 vs 45.72 +/- 5.48 g/L, respectively, P < 0.05), whereas prealbumin and transferrin were not significantly different between the groups. QoL improved after food exclusion (P < 0.05). Conclusions: An IgG-guided exclusion diet ameliorated UC symptoms and improved QoL. Interactions between IgG based food intolerance and UC warrant further study. PMID- 29788290 TI - BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins. AB - Interest in secondary metabolites such as RiPPs (ribosomally synthesized and posttranslationally modified peptides) is increasing worldwide. To facilitate the research in this field we have updated our mining web server. BAGEL4 is faster than its predecessor and is now fully independent from ORF-calling. Gene clusters of interest are discovered using the core-peptide database and/or through HMM motifs that are present in associated context genes. The databases used for mining have been updated and extended with literature references and links to UniProt and NCBI. Additionally, we have included automated promoter and terminator prediction and the option to upload RNA expression data, which can be displayed along with the identified clusters. Further improvements include the annotation of the context genes, which is now based on a fast blast against the prokaryote part of the UniRef90 database, and the improved web-BLAST feature that dynamically loads structural data such as internal cross-linking from UniProt. Overall BAGEL4 provides the user with more information through a user-friendly web-interface which simplifies data evaluation. BAGEL4 is freely accessible at http://bagel4.molgenrug.nl. PMID- 29788289 TI - Sodium chloride decreases cadmium accumulation and changes the response of metabolites to cadmium stress in the halophyte Carpobrotus rossii. AB - Background and Aims: Salinity affects the bioavailability of cadmium (Cd) in soils and Cd accumulation in plants, but the associated mechanisms remain unclear. This study aimed to assess the metabolic response to NaCl and Cd and the relationship between metabolites and Cd accumulation in the halophyte Carpobrotus rossii, which has potential for Cd phytoextraction. Methods: Plants were grown in nutrient solution with 0-400 mm NaCl in the presence of 5 or 15 um Cd, with varied or constant solution Cd2+ activity. Plant growth and Cd uptake were measured, and the accumulation of peptides, and organic and amino acids in plant tissues were assessed. Key Results: The addition of NaCl to Cd-containing solutions improved plant growth along with 70-87 % less shoot Cd accumulation, resulting from decreases in Cd root uptake and root-to-shoot translocation irrespective of Cd2+ activity in solutions. Moreover, Cd exposure increased the concentration of phytochelatins, which correlated positively with Cd concentrations in plants regardless of NaCl addition. In comparison, Cd inhibited the synthesis of organic acids in shoots and roots in the absence of NaCl, but increased it in shoots in the presence of NaCl. While Cd increased the concentrations of amino acids in plant shoots, the effect of NaCl on the synthesis of amino acids was inconsistent. Conclusions: Our data provide the first evidence that NaCl decreased Cd shoot accumulation in C. rossii by decreasing Cd root uptake and root-to-shoot translocation even under constant Cd2+ activity. The present study also supports the important role of peptides and organic acids, particular of phytochelatins, in Cd tolerance and accumulation although the changes of those metabolites was not the main reason for the decreased Cd accumulation. PMID- 29788291 TI - CD1a-Expressing Monocytes as Mediators of Inflammation in Ulcerative Colitis. AB - Background: CD1a-expressing CD14+ monocytes have been identified as inducers of autoreactive T cells. In this study, the link between inflammatory and metabolic signals and CD1a-expressing monocytes in vitro and in vivo was examined, and CD1a was evaluated as a potential therapeutic target for treatment of ulcerative colitis (UC). Methods: Peripheral blood mononuclear cells (PBMCs) from UC patients and non-UC donors were incubated with phosphatidylcholine (PC) for 2 and 7 days and subjected to flow cytometric analysis. Triacylglycerol (TAG) and cholesterol levels and frequencies of CD14+ CD1a+ monocytes were determined in a mouse model of UC that is based on NOD/scid IL2Rgammanull mice reconstituted with PBMCs from UC patients (NSG-UC). NSG-UC mice were treated with anti-CD1a antibodies. Response to treatment was determined by clinical and histological scores, flow cytometric analysis of human leucocytes from the spleen and colon, and expression levels of TGFbeta1, HGF, IFNgamma, and TARC. Results: Incubation of PBMCs with PC resulted in an increase of the frequency of CD1a+ CD14+ monocytes at the expense of CCR2-, CD86-, and TSLPR-expressing CD14+ monocytes. CD1a+ CD14+ monocytes induced the activation of CD4+ T cells and differentiation of Th cells. In vivo, TAG and cholesterol levels increased upon inflammation and correlated positively with CD14+ CD1a+ monocytes. NSG-UC mice benefitted from treatment with anti-CD1a antibodies, as indicated by a reduced histological score and reduced frequencies of CD1a+ CD14+ monocytes in the colon and spleen of mice. Conclusion: CD1a-expressing monocytes might act as sensors and mediators of inflammation in UC. Mice benefitted from treatment with anti-CD1a antibodies. PMID- 29788293 TI - The efficacy of social cognitive theory-based self-care intervention for rational antibiotic use: a randomized trial. AB - Background: Misuse of antibiotics can be described as a failure to complete treatment, skipping of the doses and reuse of leftover medicines and overuse of antibiotics. Health education interventions are expected to enhance awareness and general belief on rational antibiotics use. Therefore, the study aimed to determine the efficacy of social cognitive theory (SCT)-based self-care intervention for rational antibiotic use. Methods: This randomized trial was conducted in a sample of 260 adults. The study participants were randomly assigned as the intervention (n=130) and a control (n=130) groups. The intervention group received self-care educational intervention of four sessions lasting 45-60 min augmented with the text messages and the control groups attended usual education program in health centers. The study participants were invited to complete questionnaires at the baseline and end of the intervention. The data were analyzed using SPSS version 23.0. Chi-square (X2), independent t test and covariance analysis were used for data analysis. P<0.05 was considered statistically significant. Results: After the intervention, all SCT constructs revealed significant differences in the intervention group compared with control groups (P<0.001). Awareness and general beliefs of rational antibiotic use showed a significant difference in intervention group before and after six months (P<0.001) whereas in control group no significant differences (P>0.05). Conclusion: The study suggested that tailored appropriate educational programs based on SCT constructs can reflect a positive impact on appropriate antibiotics use. Therefore, a tailored health promotion intervention should be provided to enhance the awareness and general beliefs of the target groups. PMID- 29788292 TI - Biological Processes Modulating Longevity across Primates: A Phylogenetic Genome Phenome Analysis. AB - Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity. PMID- 29788294 TI - Epigallocatechin-3-gallate protected vanadium-induced eggshell depigmentation via P38MAPK-Nrf2/HO-1 signaling pathway in laying hens. AB - It has been demonstrated that tea polyphenol (TP) epigallocatechin-3-gallate (EGCG) can confer protection against vanadium (V) toxicity in laying hens; however, our understanding of the molecular mechanisms beyond this effect are still limited. In this study, 360 hens were randomly assigned to the 3 groups to study whether the potential mechanism P38MAPK-Nrf2/HO-1 signaling pathway is involved in the protective effect of EGCG on eggshell pigmentation in vanadium challenged laying hens. Treatments included a control group, a 10 mg/kg V (V10), and a V10 plus 130 mg/kg of EGCG group (V10+EGCG130). Both eggshell color and protoporphyrin IX were decreased in the V10 group compared with the control diet, while EGCG130 treatment partially improved shell color and protoporphyrin IX (P < 0.05). The V10 exposure induced higher cell apoptosis rate and oxidative stress in birds as evidenced by the histological apoptosis status, decreased uterine glutathione-S transferase (GST) and high abundance of malondialdehyde (MDA) compared with the control group, whereas EGCG130 markedly alleviated oxidative stress via reducing MDA generation (P < 0.05). Dietary vanadium reduced ferrochelatase, NF-E2-related factor 2 (Nrf2), and heme oxygenase (HO-1) mRNA expression, while EGCG up-regulated Nrf2 and HO-1 expression (P < 0.05). Protein levels of Nrf2, HO-1 and phospho-p38 (P-P38) MAPK were reduced in V10 group, while dietary supplementation with 130 mg/kg EGCG markedly increased Nrf2, HO-1 and P-P38 MAPK protein levels in the uterus compared with the V10 group (P < 0.01). In conclusion, EGCG improved eggshell color and antioxidant system in V10 challenged hens, which seems to be associated with P38MAPK-Nrf2/HO-1 signaling pathway. PMID- 29788296 TI - Comparison of C. difficile Stool Toxin Concentrations in Adults with Symptomatic Infection and Asymptomatic Carriage using an Ultrasensitive Quantitative Immunoassay. AB - Background: We used an ultrasensitive, quantitative Single Molecule Array (Simoa) immunoassay to test whether concentrations of C. difficile toxins A and/or B in the stool of adult inpatients with CDI were higher than in asymptomatic carriers of toxinogenic C. difficile. Methods: Patients enrolled as CDI-NAAT had clinically significant diarrhea and positive nucleic acid amplification testing (NAAT), per US guidelines, and received CDI treatment. Potential carriers had recently received antibiotics and did not have diarrhea; positive NAAT confirmed carriage. Baseline stool samples were tested by Simoa for toxin A and B. Results: Stool toxin concentrations in both CDI-NAAT (n = 122) and Carrier-NAAT (n =44) cohorts spanned five logs (0 pg/mL to >100,000 pg/mL). 79/122 (65%) CDI-NAAT and 34/44 (77%) Carrier-NAAT had toxin A+B concentration >20 pg/mL (clinical cutoff). Median toxin A, toxin B, toxin A+B and NAAT Ct values in CDI-NAAT and Carrier NAAT cohorts were similar (toxin A, 50.6 vs 60.0 pg/mL, p=0.959; toxin B, 89.5 vs 42.3 pg/mL, p=0.788; toxin A+B, 197.2 vs 137.3 pg/mL, p=0.766; Ct, 28.1 vs 28.6, p=0.354). However, when CDI/Carrier cohorts were limited to those with detectable toxin, respective medians were significantly different (A, 874.0 vs 129.7, p=0.021; B, 1317.0 vs 81.7, p=0.003, A+B, 4180.7 vs 349.6, p=0.004; Ct, 25.8 vs 27.7, p=0.015). Conclusions: Toxin concentration did not differentiate an individual with CDI from one with asymptomatic carriage. Median stool toxin concentrations in groups with CDI versus carriage differed, but only when groups were defined by detectable stool toxin (versus positive NAAT). PMID- 29788297 TI - Influence of feeding direct-fed microbial supplementation on growth performance and feeding behavior in naturally fed and conventionally fed finishing cattle with different dietary adaptation periods. AB - To determine the effects of finishing system (conventional vs. natural), dietary adaptation length (14 vs. 28 d), and direct-fed microbial (DFM) supplementation (no DFM vs. DFM) on growth performance and feeding behavior, 120 yearling steers (390 +/- 2.8 kg) were used in a completely randomized design with a 2 * 2 * 2 factorial arrangement of treatments. Feed intake was monitored using the Insentec feeding system. Blood samples were collected every 28 d. After 140 d on feed, steers were slaughtered and carcass characteristics collected. Conventionally fed steers had greater (P <= 0.001) final BW, carcass weight, and dressing %. Dry matter intake was not influenced (P >= 0.31) by treatment. Length of dietary adaptation period did not influence (P >= 016) final BW, ADG, and G:F. There was a feeding system * DFM interaction (P <= 0.02) for ADG and G:F with conventionally fed steers fed DFM having the greatest (P <= 0.05) and naturally fed steers supplemented with DFM having the least (P <= 0.05) ADG and G:F. Number of visits to the feed bunk and number of meals per day did not differ (P > 0.05) among treatments. Time eating per visit and per meal was greater (P = 0.05) in steers supplemented with DFM than in steers not supplemented with DFM. On day 56 and 140, plasma glucose concentration was greater (P <= 0.03) in steers adapted in 14 d than in steers adapted in 28 d. On day 84, plasma glucose concentration was greater (P = 0.02) in naturally fed compared to conventionally fed steers. On day 112, there was a dietary adaptation period * DFM interaction (P = 0.004) for plasma glucose concentration with glucose concentration greatest (P <= 0.05) in steers adapted in 14 d supplemented with DFM and in steers adapted in 28 d not supplemented with DFM, least for steers adapted in 28 d supplemented with DFM, with steers adapted in 14 d not supplemented with DFM intermediate (P <= 0.05). On day 112 and 140, plasma urea N concentration was greater (P <= 0.05) in steers adapted in 28 d than in steers adapted in 14 d. These data indicate that conventionally fed steers generally had improved growth performance compared to naturally fed steers. Length of dietary adaptation and DFM supplementation had minimal effects on growth performance but did interact with feeding system to influence feeding behavior and blood metabolite concentrations. PMID- 29788295 TI - Intrinsic Functional Connectivity Resembles Cortical Architecture at Various Levels of Isoflurane Anesthesia. AB - Cortical single neuron activity and local field potential patterns change at different depths of general anesthesia. Here, we investigate the associated network level changes of functional connectivity. We recorded ongoing electrocorticographic (ECoG) activity from temporo-parieto-occipital cortex of 6 ferrets at various levels of isoflurane/nitrous oxide anesthesia and determined functional connectivity by computing amplitude envelope correlations. Through hierarchical clustering, we derived typical connectivity patterns corresponding to light, intermediate and deep anesthesia. Generally, amplitude correlation strength increased strongly with depth of anesthesia across all cortical areas and frequency bands. This was accompanied, at the deepest level, by the emergence of burst-suppression activity in the ECoG signal and a change of the spectrum of the amplitude envelope. Normalization of functional connectivity to the distribution of correlation coefficients showed that the topographical patterns remained similar across depths of anesthesia, reflecting the functional association of the underlying cortical areas. Thus, while strength and temporal properties of amplitude co-modulation vary depending on the activity of local neural circuits, their network-level interaction pattern is presumably most strongly determined by the underlying structural connectivity. PMID- 29788299 TI - Petar M. Seferovic new HFA President. PMID- 29788298 TI - Cardiac diagnostic work-up of ischaemic stroke. AB - Cardioembolic sources account for 20-30% of ischaemic strokes and are important to identify considering their prognostic and therapeutic implications. During the past years, new developments have been made in the cardiac diagnostic evaluation and management of patients with ischaemic stroke, especially regarding strokes of unknown aetiology. These recent advances have had a major impact on our understanding of embolic strokes, their diagnostic work-up, and clinical management. Herein, we propose a cardiac diagnostic work-up scheme for patients with ischaemic stroke from definite cardioembolic sources and embolic strokes of undetermined source. PMID- 29788300 TI - Heart failure in Diabetic patients. PMID- 29788301 TI - The Comprehensive Heart Failure Centre in Wurzburg, Germany. PMID- 29788302 TI - John McMurray MD FESC. PMID- 29788303 TI - Professor Stuart Cook and IL-11. PMID- 29788304 TI - Measuring the unmeasurable: assessing the quality of science and scientists. PMID- 29788305 TI - Mechanisms and outcomes of heart failure: from HFpEF, HFmrEF, and HFrEF to transplantation. PMID- 29788307 TI - US Black Women and Human Immunodeficiency Virus Prevention: Time for New Approaches to Clinical Trials. PMID- 29788306 TI - Pregnancy-Onset Inflammatory Bowel Disease: A Subtle Diagnosis. AB - Background: Inflammatory bowel diseases (IBDs) are commonly diagnosed during the reproductive years. IBD first manifested during pregnancy (pregnancy-onset IBD [POIBD]) is still an undescribed entity. The aim of the study was to evaluate the characteristics and maternal and neonatal outcomes of patients with POIBD. Methods: Data of all pregnant women with IBD within a single multidisciplinary referral clinic, IBD-MOM, between 2011-2016, were analyzed. Maternal and neonatal characteristics and outcomes were compared between the POIBD group and those diagnosed before pregnancy (non-POIBD). Results: We identified 237 women, 31 (15%) from the POIBD group and 206 (85%) from the non-POIBD group. Eight (3.5%) patients experienced early spontaneous pregnancy loss, all in the non-POIBD group. The POIBD diagnosis occurred in 16 (52%) patients during the first trimester, 10 (32%) in second trimester, and 5 (16%) during third trimester. Diagnosis of ulcerative colitis (UC) was significantly more common in the POIBD group compared with the non-POIBD group (22/31, 71% vs 50/206, 24%, respectively, P < 0.001). More UC than Crohn's disease patients had active disease during pregnancy (69% vs 50%, P = 0.03, respectively). POIBD patients experienced vaginal delivery in 100% of births, compared with 164 (79.6%) in the non-POIBD group (P = 0.017). The mean gestational age at birth and the neonatal weight were similar among the study groups; 38.6 weeks and 3040 g for POIBD patients, compared with 38.7 weeks and 3055 g in the non-POIBD group. Conclusions: POIBD is a unique clinical entity, and the diagnosis is mostly UC. However, the maternal and neonatal outcomes are similar. PMID- 29788308 TI - PheProb: probabilistic phenotyping using diagnosis codes to improve power for genetic association studies. AB - Objective: Standard approaches for large scale phenotypic screens using electronic health record (EHR) data apply thresholds, such as >=2 diagnosis codes, to define subjects as having a phenotype. However, the variation in the accuracy of diagnosis codes can impair the power of such screens. Our objective was to develop and evaluate an approach which converts diagnosis codes into a probability of a phenotype (PheProb). We hypothesized that this alternate approach for defining phenotypes would improve power for genetic association studies. Methods: The PheProb approach employs unsupervised clustering to separate patients into 2 groups based on diagnosis codes. Subjects are assigned a probability of having the phenotype based on the number of diagnosis codes. This approach was developed using simulated EHR data and tested in a real world EHR cohort. In the latter, we tested the association between low density lipoprotein cholesterol (LDL-C) genetic risk alleles known for association with hyperlipidemia and hyperlipidemia codes (ICD-9 272.x). PheProb and thresholding approaches were compared. Results: Among n = 1462 subjects in the real world EHR cohort, the threshold-based p-values for association between the genetic risk score (GRS) and hyperlipidemia were 0.126 (>=1 code), 0.123 (>=2 codes), and 0.142 (>=3 codes). The PheProb approach produced the expected significant association between the GRS and hyperlipidemia: p = .001. Conclusions: PheProb improves statistical power for association studies relative to standard thresholding approaches by leveraging information about the phenotype in the billing code counts. The PheProb approach has direct applications where efficient approaches are required, such as in Phenome-Wide Association Studies. PMID- 29788309 TI - Rethinking the outpatient medication list: increasing patient activation and education while architecting for centralization and improved medication reconciliation. AB - Objective: Identify barriers impacting the time consuming and error fraught process of medication reconciliation. Design and implement an electronic medication management system where patient and trusted healthcare proxies can participate in establishing and maintaining an inclusive and up-to-date list of medications. Methods: A patient-facing electronic medication manager was deployed within an existing research project focused on elder care management funded by the AHRQ, InfoSAGE, allowing patients and patients' proxies the ability to build and maintain an accurate and up-to-date medication list. Free and open-source tools available from the U.S. government were used to embed the tenets of centralization, interoperability, data federation, and patient activation into the design. Results: Using patient-centered design and free, open-source tools, we implemented a web and mobile enabled patient-facing medication manager for complex medication management. Conclusions: Patient and caregiver participation are essential to improve medication safety. Our medication manager is an early step towards a patient-facing medication manager that has been designed with data federation and interoperability in mind. PMID- 29788310 TI - Trajectories of Aging among US Older Adults: Mixed Evidence for a Hispanic Paradox. AB - Objectives: A well-documented paradox is that Hispanics tend to live longer than non-Hispanic Whites (NHW), despite structural disadvantages. We evaluate whether the "Hispanic paradox" extends to more comprehensive longitudinal aging classifications and examine how lifecourse factors relate to these groupings. Methods: We used biennial data (1998-2014) on adults 65-years and older at baseline from the Health and Retirement Study. We use joint latent class discrete time and growth curve modeling to identify trajectories of aging, and multinomial logit models to determine whether US-born (USB-H) and Foreign-born (FB-H) Hispanics experience healthier styles of aging than non-Hispanic Whites (NHW), and test how lifecycle factors influence this relationship. Results: We identify four trajectory classes including, "cognitive unhealthy," "high morbidity," "non accelerated", and "healthy." Compared to NHWs, both USB-H and FB-H have higher relative risk ratios (RRR) of "cognitive unhealthy" and "high morbidity" classifications, relative to "non-accelerated." These patterns persist upon controlling for lifecourse factors. Both Hispanic groups, however, also have higher RRRs for "healthy" classification (vs. "non-accelerated") upon adjusting for adult achievements and health behaviors. Discussion: Controlling for lifefcourse factors USB-H and FB-H have equal or higher likelihood for "high morbidity" and "cognitive unhealthy" classifications, respectively, relative to NHWs. Yet, both groups are equally likely of being in the "healthy" group compared to NHWs. These segregations into healthy and unhealthy groups require more research and could contribute to explaining the paradoxical patterns produced when population heterogeneity is not taken into account. PMID- 29788312 TI - The Composite Spreader Flap. AB - Background: The effect of a spreader flap on the keystone area and the upper bony vault depends on the structural strength and cephalic extent of upper lateral cartilages, both of which can be significantly variable among individuals. Objectives: The authors present a novel cephalically extended osseocartilaginous composite spreader flap technique that was designed to overcome the limitations of a conventional spreader flap on the keystone area upper bony vault, in patients with cephalically short and structurally weak upper lateral cartilages and thin nasal bones. Methods: This study was a retrospective review of the recorded perioperative information to investigate the frequency of the use of the composite spreader flap technique and perioperative parameters that relate to postoperative dorsal deformities. 176 consecutive primary open approach rhinoplasty cases performed by the first author (O. B.) between November 2015 and February 2017 were included in the study. Patient data was obtained from rhinoplasty data sheets, standardized photographs and postoperative physical examinations. Results: Of the 176 cases who underwent primary open approach rhinoplasty whose data were reviewed for the purpose of this study, 38 (32 females, 6 males) had dorsal reconstruction with the use of a composite spreader flap. 17 patients had a deviated nose with an asymmetric bony pyramid. In 8 patients, composite spreader flap was used unilaterally. No patients in the composite spreader flap group had a postoperative dorsal deformity or required surgical revision. Conclusions: Composite flap preparation extends the reliability and the reach of the spreader flap technique beyond its previous borders. PMID- 29788313 TI - Defining Value of Cancer Therapeutics-A Health System Perspective. AB - Because of the rising costs of cancer care and ongoing challenges in ensuring access to quality care, there is an increasing need to prioritize spending and define the benefits of therapy in proportion to costs. The term "value" has gained favor as means to define the relative utility of a medical intervention in terms of benefits, risks, and financial costs, which in turn can help clinicians, patients, and policy makers prioritize "high-value" care. While numerous value concepts have been proposed, a comprehensive discussion of value initiatives along the care continuum is missing. In this Commentary, we propose a health system taxonomy of value initiatives in cancer care to discuss what the field needs to progress. PMID- 29788311 TI - Adipose tissue proteomic analyses to study puberty in Brahman heifers. AB - The adipose tissue has been recognized as an active endocrine organ which can modulate numerous physiological processes such as metabolism, appetite, immunity, and reproduction. The aim of this study was to look for differentially abundant proteins and their biological functions in the abdominal adipose tissue between pre- and postpubertal Brahman heifers. Twelve Brahman heifers were divided into 2 groups and paired on slaughter day. Prepubertal heifers had never ovulated and postpubertal heifers were slaughtered on the luteal phase of their second estrous cycle. After ensuring the occurrence of puberty in postpubertal heifers, abdominal adipose tissue samples were collected. Mass spectrometry proteomic analysis identified 646 proteins and revealed that 171 proteins showed differential abundance in adipose tissue between the pre- and postpuberty groups (adjusted P-value < 0.05). Data are available via ProteomeXchange with identifier PXD009452. Using a list of 51 highly differentially abundant proteins as the target (adjusted P-value < 10-5), we found 14 enriched pathways. The results indicated that gluconeogenesis was enhanced when puberty approached. The metabolism of glucose, lipids, and AA in the adipose tissue mainly participated in oxidation and energy supply for heifers when puberty occurred. Our study also revealed the differentially abundant proteins were enriched for estrogen signaling and PI3K-Akt signaling pathways, which are known integrators of metabolism and reproduction. These results suggest new candidate proteins that may contribute to a better understanding of the signaling mechanisms that relate adipose tissue function to puberty. Protein-protein interaction network analysis identified 4 hub proteins that had the highest degrees of connection: PGK1, ALDH5A1, EEF2, and LDHB. Highly connected proteins are likely to influence the functions of all differentially abundant proteins identified, directly or indirectly. PMID- 29788314 TI - Patterns of E-Cigarette Use Among Youth and Young Adults: Review of the Impact of E-Cigarettes on Cigarette Smoking. AB - Implications: The present article provides a review of the impact of e-cigarette use on subsequent cigarette smoking among youth and YAs. Studies presented here suggest that e-cigarette use among non-smokers is associated with subsequent cigarette smoking, but study designs are subject to numerous limitations. Future research should focus on addressing the characteristics that put youth and YAs at risk of using either product and how appeal and accessibility of these products are related to product use in order to inform future policy-making. PMID- 29788315 TI - Inferring and modeling inheritance of differentially methylated changes across multiple generations. PMID- 29788316 TI - Efficacy of Vaginally Administered Gel Containing Emtricitabine and Tenofovir Against Repeated Rectal Simian Human Immunodeficiency Virus Exposures in Macaques. AB - Vaginal microbicides containing antiretrovirals (ARVs) have shown to prevent vaginally acquired human immunodeficiency virus (HIV), but these products may not protect women who engage in anal sex. Intravaginal dosing with ARVs has shown to result in drug exposures in rectal tissues, thus raising the possibility of dual compartment protection. To test this concept, we investigated whether intravaginal dosing with emtricitabine (FTC)/tenofovir (TFV) gel, which fully protected macaques against repeated vaginal exposures to simian human immunodeficiency virus (SHIV), protects against rectal SHIV exposures. Pharmacokinetic studies revealed rapid distribution of FTC and TFV to rectal tissues and luminal fluids, albeit at concentrations 1-2 log10 lower than those in the vaginal compartment. Efficacy measurements against repeated rectal SHIV challenges demonstrated a 4.5-fold reduction in risk of infection in macaques that received intravaginal FTC/TFV compared to placebo gel (P = .047; log-rank test). These data support the concept of dual compartment protection by vaginal dosing and warrants developing ARV-based vaginal products with improved bidirectional dosing. PMID- 29788317 TI - FragFit: a web-application for interactive modeling of protein segments into cryo EM density maps. AB - Cryo-electron microscopy (cryo-EM) is a standard method to determine the three dimensional structures of molecular complexes. However, easy to use tools for modeling of protein segments into cryo-EM maps are sparse. Here, we present the FragFit web-application, a web server for interactive modeling of segments of up to 35 amino acids length into cryo-EM density maps. The fragments are provided by a regularly updated database containing at the moment about 1 billion entries extracted from PDB structures and can be readily integrated into a protein structure. Fragments are selected based on geometric criteria, sequence similarity and fit into a given cryo-EM density map. Web-based molecular visualization with the NGL Viewer allows interactive selection of fragments. The FragFit web-application, accessible at http://proteinformatics.de/FragFit, is free and open to all users, without any login requirements. PMID- 29788319 TI - Participatory Design in Gerontechnology: A Systematic Literature Review. AB - Purpose of the Study: Participatory design (PD) is widely used within gerontechnology but there is no common understanding about which methods are used for what purposes. This review aims to examine what different forms of PD exist in the field of gerontechnology and how these can be categorized. Design and Methods: We conducted a systematic literature review covering several databases. The search strategy was based on 3 elements: (1) participatory methods and approaches with (2) older persons aiming at developing (3) technology for older people. Results: Our final review included 26 studies representing a variety of technologies designed/developed and methods/instruments applied. According to the technologies, the publications reviewed can be categorized in 3 groups: Studies that (1) use already existing technology with the aim to find new ways of use; (2) aim at creating new devices; (3) test and/or modify prototypes. The implementation of PD depends on the questions: Why a participatory approach is applied, who is involved as future user(s), when those future users are involved, and how they are incorporated into the innovation process. Implications: There are multiple ways, methods, and instruments to integrate users into the innovation process. Which methods should be applied, depends on the context. However, most studies do not evaluate if participatory approaches will lead to a better acceptance and/or use of the co-developed products. Therefore, participatory design should follow a comprehensive strategy, starting with the users' needs and ending with an evaluation if the applied methods have led to better results. PMID- 29788318 TI - Effectiveness and Safety of Vedolizumab in Anti-TNF-Naive Patients With Inflammatory Bowel Disease-A Multicenter Retrospective European Study. AB - Background: Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti TNF)-naive patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naive patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naive patients in an RWE setting. Methods: This retrospective multicenter European pooled cohort study included consecutive active anti-TNF naive IBD patients treated with VDZ. The primary end point was clinical response at week 14. Patients with follow-up beyond week 14 and those discontinuing VDZ at any time were included for maintenance outcomes analysis. Results: Since January 2015, 184 anti-TNF-naive patients from 23 centers initiated VDZ treatment (Crohn's disease [CD], 50; ulcerative colitis [UC], 134). In CD, 42/50 (82%) patients responded by week 14 and 32 (64%) were in clinical remission; 26/50 (52%) achieved corticosteroid-free remission (CSFR). At last follow-up (44 weeks; interquartile range [IQR], 30-52 weeks), 27/35 (77.1%) patients with available data responded to treatment; 24/35 (68.6%) were in clinical remission, 21/35 (60%) were in CSFR. For UC, 116/134 (79.1%) responded to treatment by week 14, including 53 (39.5%) in clinical remission; 49/134 (36.6%) achieved CSFR. At last follow-up (42.5 weeks; IQR, 30-52 weeks), 79/103 (76.7%) patients responded to treatment, 69/103 (67.0%) were in remission, and 61/103 (59.2%) were in CSFR. Adverse effects were reported in 20 (11%) of the patients, leading to treatment discontinuation in 6 (3.3%). Conclusions: VDZ is similarly effective in ant-TNF naive CD and UC patients. The efficacy is higher than reported in anti-TNF experienced patients and is comparable to that of anti-TNF biologics in this population. PMID- 29788320 TI - Chronic Variable Stress Induces Sex-Specific Alterations in Social Behavior and Neuropeptide Expression in the Mouse. AB - Chronic exposure to stressors impairs the function of multiple organ systems and has been implicated in increased disease risk. In the rodent, the chronic variable stress (CVS) paradigm has successfully modeled several stress-related illnesses. Despite striking disparities between men and women in the prevalence and etiology of disorders associated with chronic stress, most preclinical research examining chronic stressor exposure has focused on male subjects. One potential mediator of the consequences of CVS is oxytocin (OT), a known regulator of stress neurocircuitry and behavior. To ascertain the sex-specific effects of CVS in the C57BL/6 mouse on OT and the structurally similar neuropeptide arginine vasopressin (AVP), the numbers of immunoreactive and mRNA-containing neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) were determined using immunohistochemistry and in situ hybridization, respectively. In addition, the mice underwent a battery of behavioral tests to determine whether CVS affects social behaviors known to be regulated by OT and AVP. Six weeks of CVS increased sociability in the female mouse and decreased PVN OT immunoreactivity (ir) and AVP mRNA. In the male mice, CVS decreased PVN OT mRNA but had no effect on social behavior, AVP, or OT-ir. CVS also increased the soma volume for PVN OT neurons. In contrast, OT and AVP neurons in the SON were unaffected by CVS treatment. These findings demonstrate clear sex differences in the effects of CVS on neuropeptides in the mouse, suggest a pathway through which CVS alters sociability and stress-coping responses in females and reveals a vulnerability to CVS in the C57BL/6 mouse strain. PMID- 29788322 TI - Outcomes and risk factors associated with tricuspid valve repair in children with hypoplastic left heart syndrome. AB - : OBJECTIVES: Tricuspid valve (TV) competence is important for successful palliation of hypoplastic left heart syndrome (HLHS). We report our experience with TV repair in HLHS patients with a focus on TV and right ventricular (RV) function and associated clinical outcomes. METHODS: From 2002 to 2012, 219 neonates with HLHS underwent the Norwood operation. Thirty patients who underwent TV repair at various stages comprised our current series cohort. Echocardiographic and clinical data were reviewed to determine the effectiveness of TV repair and outcomes of the patients. RESULTS: Thirty patients received TV repair during Norwood (n = 4), Glenn (n = 17) and Fontan (n = 9) operations. Median age at TV repair was 188 days (range 3-1498). Preoperatively, all patients had >=moderate TV regurgitation and 4 (13%) patients had >=moderate RV dysfunction. After repair, TV regurgitation was none or trivial (n = 12, 40%), mild (n = 8, 27%), >=moderate (n = 10, 33%), whereas 10 (33%) had >=moderate regurgitation at last follow-up; >=moderate RV dysfunction was present in 5 (17%) patients following TV repair and 10 (33%) patients at last follow-up. Competing risk analysis showed that 10 years following TV repair, 21% of patients had TV reoperation, 18% died or underwent transplantation and 61% were alive without subsequent reoperation. Overall, 10-year survival, transplant-free survival and freedom from second TV reoperation were 89%, 71% and 78%, respectively; >=moderate RV dysfunction following TV repair was associated with diminished transplant-free survival (P = 0.0277). CONCLUSIONS: Although TV repair is successful in reducing regurgitation in the majority of HLHS patients, outcomes are restricted by limited repair durability with recurrent significant regurgitation in one-third of the patients. RV dysfunction in these patients is progressive and a major determinant of transplant-free survival. PMID- 29788321 TI - Presentation of oropharyngeal dysphagia and rehabilitative intervention following esophagectomy: a systematic review. AB - No study has systematically reviewed the evidence on presentation of oropharyngeal dysphagia and swallowing rehabilitation following esophagectomy. The purposes of this systematic review are to 1) qualitatively synthesize the current findings on oropharyngeal swallowing abnormalities identified by instrumental swallowing evaluations, 2) describe the reported health-related outcomes in relation to swallowing abnormality following esophagectomy, and 3) examine the efficacy of reported rehabilitative interventions for oropharyngeal dysphagia in patients who underwent esophagectomy. Publications were searched using five electronic databases. No language or publication date restrictions were imposed. Two authors performed a blind review for published or unpublished studies that reported swallowing biomechanics and dysphagic symptoms using instrumental evaluation of swallowing, specifically the videofluoroscopic swallowing study and fiberoptic endoscopic evaluation of swallowing, and/or health-related outcomes in relation to swallowing abnormalities, and/or therapeutic interventions for oropharyngeal dysphagia following esophagectomy. Twelve studies out of 2,193 studies including 458 patients met the inclusion criteria. Reported abnormal swallowing biomechanics included vocal fold immobility, delayed onset of swallowing, reduced hyolaryngeal elevation, and reduced opening of the upper esophageal sphincter. Aspiration (0-81%) and pharyngeal residue (22-100%) were prevalent. Those abnormal swallowing biomechanics and swallowing symptoms were commonly reported following both transhiatal and transthoracic esophagectomy. Pneumonia presented in 5-25% of the study patients. One quasi-experimental study examined the effectiveness of swallowing exercises for postoperative oropharyngeal dysphagia; three case series reported a benefit of the chin-tuck maneuver in reducing aspiration and residue. This review revealed distinct swallowing impairments and increased pneumonia risks following esophagectomy. This review also found that evidence on the efficacy of therapeutic interventions was limited. Future studies are warranted to develop effective rehabilitative interventions for postesophagectomy patients with oropharyngeal dysphagia. PMID- 29788323 TI - Development and Psychometric Properties of the Inflammatory Bowel Disease Distress Scale (IBD-DS): A New Tool to Measure Disease-Specific Distress. AB - Background: Inflammatory bowel disease (IBD) imposes a heavy psychosocial burden, with many patients reporting anxiety, depression, and distress. In diseases such as diabetes, disease-specific distress is associated with concordance with treatments and disease control. IBD distress, distinct from anxiety and depression, is evident in people with IBD. We aimed to develop a questionnaire for assessing IBD-specific distress, validate this against a gold standard distress measure for diabetes, and demonstrate the difference between anxiety, depression, and distress. Methods: The 94-item IBD Distress Scale (IBD-DS) was developed through secondary analysis of 3 qualitative data sets from previous IBD studies. Items were then refined through cognitive interviews in 2 stages (n = 15, n = 3). Three supplementary unscored questions were added to enable patients to identify their overall level of distress, their perceived level of disease activity, and their 3 most distressing issues. Subsequently, the 55-item IBD Distress Scale was subjected to test-retest. Two hundred seventy-five people received the test draft IBD-DS, and 168 responded (60.4%). Of these, 136 (82%) returned the retest draft of IBD-DS 3 weeks later. After analysis, further item reduction was informed by response rates, kappa values, and correlation coefficients, and test-retest was repeated. One hundred fifty-four people received the test final 28-item IBD-DS, and 123 people responded (58.8%). Of these, 95 (77%) returned the retest final IBD-DS. Results: The 94 items were reduced to 28 items. Good intraclass correlation (ICC) was found between test retest scores on 72 complete data sets with unchanged disease status (ICC, 0.92; 95% confidence interval, 0.88-0.95). Cronbach's alpha was 0.95, indicating excellent internal consistency. Factor analysis indicated scoring the items as a single domain (score range, 0-168). Conclusion: The final IBD-DS performs well and offers a tool for assessing IBD-specific distress. PMID- 29788324 TI - The Application of COI Gene for Species Identification of Forensically Important Muscid Flies (Diptera: Muscidae). AB - Muscid Flies (Diptera: Muscidae) are of great forensic importance due to their wide distribution, ubiquitous and synanthropic nature. They are frequently neglected as they tend to arrive at the corpses later than the flesh flies and blow flies. Moreover, the lack of species-level identification also hinders investigation of medicolegal purposes. To overcome the difficulty of morphological identification, molecular method has gained relevance. Cytochrome c oxidase subunit I (COI) gene has been widely utilized. Nonetheless, to achieve correct identification of an unknown sample, it is important to survey certain muscid taxa from its geographic distribution range. Accordingly, the aim of this study is to contribute more geographically specific. We sequenced the COI gene of 51 muscid specimens of 12 species, and added all correct sequences available in GenBank to yield a total data set of 125 COI sequences from 33 muscid species to evaluate the COI gene as a molecular diagnostic tool. The interspecific distances were extremely high (4.7-19.8%) in either the standard barcoding fragment (658 bp) or the long COI sequence (1,019-1,535 bp), demonstrating that these two genetic markers were nearly identical in the species identification. However, the intraspecific distances of the long COI sequences were significantly higher than the barcoding region for the conspecific species that geographical locations vary greatly. Therefore, genetic diversity presented in this study provides a reference for species identification of muscid flies. Nevertheless, further investigation and data from more muscid species are required to enhance the efficacy of species-level identification using COI gene as a genetic marker. PMID- 29788326 TI - In situ transmission electron microscopic observations of redox cycling of a Ni ScSZ cermet fuel cell anode. AB - In situ transmission electron microscopy (TEM) observations of a Ni(O)-Sc2O3 stabilized ZrO2 (ScSZ; 10 mol% Sc2O3, 1 mol% CeO2, 89 mol% ZrO2) anode in a solid oxide fuel cell (SOFC) have been performed at high temperatures under a hydrogen/oxygen gas atmosphere using an environmental transmission electron microscope (ETEM); the specimens were removed from cross-sections of the real SOFC by focused ion beam milling and lifting. When heating the NiO-ScSZ anode under a hydrogen atmosphere of 3 mbar in ETEM, nano-pores were formed at the grain boundaries and on the surface of NiO particles at around 400 degrees C due to the volume shrinkage accompanying the reduction of NiO to Ni. Moreover, densification of Ni occurred when increasing the temperature from 600 to 700 degrees C. High-magnification TEM images obtained in the early stages of NiO reduction revealed that the (111) planes of Ni grew almost parallel to the (111) planes of NiO. In the case of heating Ni-ScSZ under an oxygen atmosphere of 3 mbar in ETEM, oxidation of Ni starting from the surface of the particles occurred above 300 degrees C. All Ni particles became polycrystalline NiO after the temperature was increased to 800 degrees C. Volume expansion/contraction by mass transfer to the outside/inside of the Ni particles in the anode during repeated oxidation/reduction seems to result in the agglomeration of Ni catalysts during long-term SOFC operation. We emphasize that our in situ TEM observations will be applied to observe electrochemical reactions in SOFCs under applied electric fields. PMID- 29788325 TI - Ancestral TCDD Exposure Induces Multigenerational Histologic and Transcriptomic Alterations in Gonads of Male Zebrafish. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the classic aryl hydrocarbon receptor (AhR) agonist, is a potent environmental toxicant and endocrine-disrupting chemical (EDC) with known developmental toxicity in humans, rodents, and fish. Early life exposure to some EDCs, including TCDD, is linked to the occurrence of adult-onset and multigenerational disease. Previous work exposing juvenile F0 zebrafish (Danio rerio) to 50 ppt (parts per trillion) TCDD during reproductive development has shown male-mediated transgenerational decreases in fertility (F0 F2) and histologic and transcriptomic alterations in F0 testes. Here, we analyzed male germline alterations in F1 and F2 adult fish, looking for changes in testicular histology and gene expression inherited through the male lineage that could account for decreased reproductive capacity. Testes of TCDD-lineage F1 fish displayed an increase in spermatogonia (immature germ cells) and decrease in spermatozoa (mature germ cells). No histological changes were present in F2 fish. Transcriptomic analysis of exposed F1 and F2 testes revealed alterations in lipid and glucose metabolism, oxidation, xenobiotic response, and sperm cell development and maintenance genes, all of which are implicated in fertility outcomes. Overall, we found that differential expression of reproductive genes and reduced capacity of sperm cells to mature could account for the reproductive defects previously seen in TCDD-exposed male zebrafish and their descendants, providing insight into the distinct multigenerational effects of toxicant exposure. PMID- 29788327 TI - Tree-ring proxies of larch bud moth defoliation: latewood width and blue intensity are more precise than tree-ring width. AB - Reconstructions of defoliation by larch bud moth (LBM, Zeiraphera diniana Gn.) based on European larch (Larix decidua Mill.) tree rings have unraveled outbreak patterns over exceptional temporal and spatial scales. In this study, we conducted tree-ring analyses on 105 increment cores of European larch from the Valais Alps, Switzerland. The well-documented history of LBM outbreaks in Valais provided a solid baseline for evaluating the LBM defoliation signal in multiple tree-ring parameters. First, we used tree-ring width measurements along with regional records of LBM outbreaks to reconstruct the occurrence of these events at two sites within the Swiss Alps. Second, we measured earlywood width, latewood width and blue intensity, and compared these parameters with tree-ring width to assess the capacity of each proxy to detect LBM defoliation. A total of six LBM outbreaks were reconstructed for the two sites between AD 1850 and 2000. Growth suppression induced by LBM was, on average, highest in latewood width (59%), followed by total ring width (54%), earlywood width (51%) and blue intensity (26%). We show that latewood width and blue intensity can improve the temporal accuracy of LBM outbreak reconstructions, as both proxies systematically detected LBM defoliation in the first year it occurred, as well as the differentiation between defoliation and non-defoliation years. This study introduces blue intensity as a promising new proxy of insect defoliation and encourages its use in conjunction with latewood width. PMID- 29788329 TI - Pharmacokinetic and Pharmacodynamic Properties of Metronidazole in Pediatric Patients With Acute Appendicitis: A Prospective Study. AB - Background: Metronidazole is traditionally dosed every 6-8 hours even though in adults it has a long half-life, concentration-dependent killing, and 3-hour postantibiotic effect. Based on this logic, some pediatric hospitals adopted once daily dosing for appendicitis, despite limited pharmacokinetics-pharmacodynamics (PK/PD) in children. We studied pediatric patients with appendicitis given metronidazole once daily to determine whether this dosing would meet target area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio of >=70 for Bacteroides fragilis. Methods: One hundred pediatric patients aged 4-17 years had an average of 3 blood draws per patient during the first 24 hours after a 30 mg/kg per dose of intravenous metronidazole. Concentrations of drug were determined using validated liquid chromatography and tandem mass spectrometry. A NONMEM model was constructed for determining PK, followed by Monte Carlo simulations to generate a population of plasma concentration-time AUC of metronidazole and hydroxy-metronidazole. Results: Simulated AUC values met target attainment (AUC/MIC ratio of >=70 to B fragilis MICs) for 96%-100% of all patients for an MIC of 2 mcg/mL. For MICs of 4 and 8 mcg/mL, target attainment ranged from 61% to 97% and 9% to 71%, respectively. Areas under the curve were similar to that of adults receiving 1000 mg and 1500 mg q24, or 500 mg q8 hours. Conclusions: Metronidazole, 30 mg/kg per dose, once daily achieved AUC target attainment for B fragilis with an MIC of 2 mcg/mL or less in pediatric appendicitis patients. Based on this and studies in adults, there does not seem to be any PK/PD advantage of more frequent dosing in this population. PMID- 29788331 TI - Clinical and Cardiac Safety of Long-term Levofloxacin in Children Treated for Multidrug-resistant Tuberculosis. AB - Safety concerns persist for long-term pediatric fluoroquinolone use. Seventy children (median age, 2.1 years) treated with levofloxacin 10-20 mg/kg once daily for multidrug-resistant tuberculosis (median observation time, 11.8 months) had few musculoskeletal events, no levofloxacin-attributed serious adverse events, and no Fridericia-corrected QT interval >450 ms. Long-term levofloxacin was safe and well tolerated. PMID- 29788330 TI - The Evolution of Gene Expression Underlying Vision Loss in Cave Animals. AB - Dissecting the evolutionary genetic processes underlying eye reduction and vision loss in obligate cave-dwelling organisms has been a long-standing challenge in evolutionary biology. Independent vision loss events in related subterranean organisms can provide critical insight into these processes as well as into the nature of convergent loss of complex traits. Advances in evolutionary developmental biology have illuminated the significant role of heritable gene expression variation in the evolution of new forms. Here, we analyze gene expression variation in adult eye tissue across the freshwater crayfish, representing four independent vision-loss events in caves. Species and individual expression patterns cluster by eye function rather than phylogeny, suggesting convergence in transcriptome evolution in independently blind animals. However, this clustering is not greater than what is observed in surface species with conserved eye function after accounting for phylogenetic expectations. Modeling expression evolution suggests that there is a common increase in evolutionary rates in the blind lineages, consistent with a relaxation of selective constraint maintaining optimal expression levels. This is evidence for a repeated loss of expression constraint in the transcriptomes of blind animals and that convergence occurs via a similar trajectory through genetic drift. PMID- 29788334 TI - Microsurgical Resection of Ruptured Large Left Temporo-Occipital Arteriovenous Malformation: 3-Dimensional Operative Video. AB - A 59-yr-old man presented with intraventricular hemorrhage and was found to have a large temporo-occipital arteriovenous malformation (AVM), Spetzler-Martin grade 4. The preoperative intra-arterial digital subtraction angiography (IADSA) showed the AVM was 4 * 4 cm2, had superficial and deep venous drainage, and was fed by multiple branches of the posterior cerebral artery and middle cerebral artery. Preoperative embolization was done in 4 stages. He underwent a left temporo occipital craniotomy, mastoidectomy, and retrosigmoid craniotomy with a posterior temporal approach. Intraoperatively, there was a large draining vein draining into the sigmoid sinus in the location of the vein of Labbe, and multiple other feeding arteries and draining veins, including periventricular vessels. Circumferential dissection of the AVM was done from posteriorly, superiorly, anteriorly, and then inferiorly. The technique of temporary clipping and cauterizing the perforating arteries, and then sectioning them after flow arrest is shown in the video. Large arterial feeders were cauterized and divided. Three permanent aneurysm clips were left to control bleeding from the vessels of the trigone of the lateral ventricle. After the large draining vein into the sigmoid sinus was occluded, the AVM was completely removed. The patient had acute nonfluent aphasia postoperatively but improved after speech therapy. The postoperative IADSA demonstrated total resection. At 3-mo follow-up, he had recovered completely (mRS0). This 3-D video shows the technical nuances of microsurgical resection of a complex large AVM. Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides. PMID- 29788335 TI - Detection of Hepatozoon canis in the Brown Dog Tick and Domestic Dogs in Peninsular Malaysia. AB - Hepatozoon canis has been widely reported in dogs. Its prevalence in ticks, however, has not been well-established. Here we determine the occurrence of Hepatozoon DNA in the brown dog tick Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) sensu lato (s.l.) and domestic dogs from Peninsular Malaysia using a polymerase chain reaction (PCR) assay based on amplification of the 18S ribosomal RNA coding sequence. Our results revealed a relatively low prevalence of H. canis DNA in both R. sanguineus s.l. (0.7%) and dogs (3.33%). This study represents the first report of H. canis DNA in R. sanguineus s.l. in Malaysia, highlighting the risk of this infection in dogs. PMID- 29788333 TI - Isolation and characterization of subgroup J Avian Leukosis virus associated with hemangioma in commercial Hy-Line chickens. AB - There was an outbreak of hemangioma associated with avian leukosis virus subgroup J (ALV-J) between 2006 and 2010 in China in commercial layer chickens. Recently, severe hemangiomas broke out in Hy-Line layer chickens on a poultry farm in 2017 where ALV was eradicated earlier. Six isolates of ALV-J, named SDAU1701-SDAU1706, were characterized by virus isolation and sequence analysis of the complete proviral genomes. Avian leukosis virus subgroup J was identified by an immunofluorescence assay with monoclonal antibody JE9, whereas Marek's disease virus or reticuloendotheliosis virus was not detected. Sequence analysis of the complete proviral genome revealed that there was 96.0-99.6% identity between each other and had a homology of 94.6-96.0% when compared with the reference strain. The six isolates formed one distinct lineage separate from the reference sequences in a phylogenetic-tree, which suggested that there were several genetic differences between these groups. Homology analysis of the env, pol, and gag genes of the six isolates showed that the env gene was more variable, especially the gp85 protein, which shared only 88.2-91.9% identity with the reference strains. Sequence comparisons of the gp85 protein indicated that 19 sites were different from those in the NX0101 and HPRS-103 strains inducing myeloid leukosis; among our strains, five mutations were identical to those in the viruses causing hemangioma. Four other distinctive mutations were detected in our six isolates. This study reminds us that the surveillance of viral eradication should be conducted continuously on a farm where ALVs were eradicated. To prevent the prevalence of ALVs, more attention should be paid to daily monitoring. PMID- 29788336 TI - Microsurgical Resection of Posterior Third Ventricular/Pineal Region Papillary Tumor Via Supracerebellar Infratentorial Approach: 3-Dimensional Operative Video. AB - The posterior third ventricle and pineal region can harbor different pathologies. The supracerebellar infratentorial approach allows a direct access to the pineal region and posterior third ventricle and provides wide exposure of the arachnoid planes and deep venous system. In this 3-dimensional video, we present a patient with posterior third ventricular/pineal region tumor who underwent microsurgical resection via supracerebellar infratentorial approach. The patient is a 28-year old woman with history of hydrocephalus who underwent endoscopic third ventriculostomy and biopsy at an outside hospital. The histopatology of the tumor was papillary tumor of the pineal region. The patient was referred for further surgical resection due to enlargement of her tumor on follow-up radiological imaging. The surgery and the patient's postoperative course were uneventful and the patient remained unchanged in the postoperative period. The important steps of the surgical approach and microsurgical resection are demonstrated in this 3 dimensional surgical video. The patient consented to publication of her images. PMID- 29788332 TI - Constitutive Interferon Pathway Activation in Tumors as an Efficacy Determinant Following Oncolytic Virotherapy. AB - Background: Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however. Methods: We performed RNA sequencing and gene set enrichment analysis to identify pathways differentially activated in MV-resistant (n = 3) and -permissive (n = 2) tumors derived from resected human glioblastoma (GBM) specimens and propagated as xenografts (PDX). Using a unique gene signature we identified, we generated a diagonal linear discriminant analysis (DLDA) classification algorithm to predict MV responders and nonresponders, which was validated in additional randomly selected GBM and ovarian cancer PDX and 10 GBM patients treated with MV in a phase I trial. GBM PDX lines were also treated with the US Food and Drug Administration-approved JAK inhibitor, ruxolitinib, for 48 hours prior to MV infection and virus production, STAT1/3 signaling and interferon stimulated gene expression was assessed. All statistical tests were two-sided. Results: Constitutive interferon pathway activation, as reflected in the DLDA algorithm, was identified as the key determinant for MV replication, independent of virus receptor expression, in MV-permissive and -resistant GBM PDXs. Using these lines as the training data for the DLDA algorithm, we confirmed the accuracy of our algorithm in predicting MV response in randomly selected GBM PDX ovarian cancer PDXs. Using the DLDA prediction algorithm, we demonstrate that virus replication in patient tumors is inversely correlated with expression of this resistance gene signature (rho = -0.717, P = .03). In vitro inhibition of the interferon response pathway with the JAK inhibitor ruxolitinib was able to overcome resistance and increase virus production (1000-fold, P = .03) in GBM PDX lines. Conclusions: These findings document a key mechanism of tumor resistance to oncolytic MV therapy and describe for the first time the development of a prediction algorithm to preselect for oncolytic treatment or combinatorial strategies. PMID- 29788337 TI - Improving the timeliness and accuracy of injury severity data in road traffic accidents in an emerging economy setting. AB - Road traffic injuries (RTIs) are among the leading causes of injury and fatality worldwide. RTI casualties are continually increasing in Taiwan; however, because of a lack of an advanced method for classifying RTI severity data, as well as the fragmentation of data sources, road traffic safety and health agencies encounter difficulties in analyzing RTIs and their burden on the healthcare system and national resources. These difficulties lead to blind spots during policy-making for RTI prevention and control. After compiling classifications applied in various countries, we summarized data sources for RTI severity in Taiwan, through which we identified data fragmentation. Accordingly, we proposed a practical classification for RTI severity, as well as a feasible model for collecting and integrating these data nationwide. This model can provide timely relevant data recorded by medical professionals and is valuable to healthcare providers. The proposed model's pros and cons are also compared to those of other current models. PMID- 29788338 TI - Clinical Pharmacology in Adult and Pediatric Inflammatory Bowel Disease. AB - This review describes the clinical pharmacology of the major drugs used for the treatment of patients with inflammatory bowel disease (IBD). Pharmacokinetics, drug metabolism, mechanism of action, efficacy, and safety profile are discussed. Some small molecules were developed to act systemically (eg, ozanimod) or locally (eg, aminosalicylates) and thus have disparate pharmacokinetic properties. In addition, locally acting compounds have been optimized to mitigate systemic exposure-eg, budesonide, which undergoes extensive first-pass metabolism-thereby reducing systemic bioavailability and side effects. Other small molecules such as thiopurines are precursors of their active metabolites and differences in genotype or phenotype of metabolizing enzymes may affect efficacy and safety, requiring therapeutic drug monitoring (TDM). Monoclonal antibodies (MAs) are large molecules administered parenterally, and their pharmacokinetics may be influenced not only by the general immunoglobulin (Ig) G metabolism and recycling pathways but also by antigen properties such as antigen distribution and antigen concentration. In addition, antibody structure, host factors, concurrent medications, and immunogenicity may contribute to the substantial inter- and intrapatient variability in drug exposure and response observed for MAs. Current guidelines recommend reactive TDM of tumor necrosis factor antagonists at the time of loss of response. Evidence for proactive TDM and for the role of TDM for biologics with a different mechanism of action is emerging. Although small molecules offer potential benefits over biologics with oral administration and lack of immunogenicity, there may be risk for more systemic side effects due to off-target binding. Understanding drug metabolism, pharmacokinetic characteristics, and mechanism of action are important in selecting the right drug at the right time at the right dose for patients with IBD.10.1093/ibd/izy189_video1izy189.video15786062223001. PMID- 29788339 TI - Rapid Establishment of a Cold Chain Capacity of -60 degrees C or Colder for the STRIVE Ebola Vaccine Trial During the Ebola Outbreak in Sierra Leone. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788340 TI - Utilizing Nurses to Staff an Ebola Vaccine Clinical Trial in Sierra Leone during the Ebola Outbreak. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788341 TI - Lessons Learned in Clinical Trial Communication During an Ebola Outbreak: The Implementation of STRIVE. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788342 TI - Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788344 TI - Comment: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). PMID- 29788343 TI - Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola. AB - : The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV?G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at <=-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788346 TI - Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788345 TI - The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV?G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788347 TI - Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788348 TI - Participant Retention in a Randomized Clinical Trial in an Outbreak Setting: Lessons From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788349 TI - Operationalizing International Regulatory Standards in a Limited-Resource Setting During an Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) Experience. AB - Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. PMID- 29788350 TI - Relationship among team dynamics, care coordination and perception of safety culture in primary care. AB - Background: There remains a need to improve patient safety in primary care settings. Studies have demonstrated that creating high-performing teams can improve patient safety and encourage a safety culture within hospital settings, but little is known about this relationship in primary care. Objective: To examine how team dynamics relate to perceptions of safety culture in primary care and whether care coordination plays an intermediating role. Research Design: This is a cross-sectional survey study with 63% response (n = 1082). Subjects: The study participants were attending clinicians, resident physicians and other staff who interacted with patients from 19 primary care practices affiliated with Harvard Medical School. Main Measures: Three domains corresponding with our main measures: team dynamics, care coordination and safety culture. All items were measured on a 5-point Likert scale. We used linear regression clustered by practice site to assess the relationship between team dynamics and perceptions of safety culture. We also performed a mediation analysis to determine the extent to which care coordination explains the relationship between perceptions of team dynamics and of safety culture. Results: For every 1-point increase in overall team dynamics, there was a 0.76-point increase in perception of safety culture [95% confidence interval (CI) 0.70-0.82, P < 0.001]. Care coordination mediated the relationship between team dynamics and the perception of safety culture. Conclusion: Our findings suggest there is a relationship between team dynamics, care coordination and perceptions of patient safety in a primary care setting. To make patients safer, we may need to pay more attention to how primary care providers work together to coordinate care. PMID- 29788351 TI - Uninterrupted apixaban for atrial fibrillation ablation is a reasonable alternative, but what is the significance of silent cerebral infarctions? PMID- 29788352 TI - Revisiting the low birthweight paradox using sibling data with implications for the classification of low birthweight. AB - Background: We examined the birthweight threshold for increased odds of neonatal death among second births based on their elder sibling's birthweight category. Methods: This population-based cohort study included 190 575 women who delivered their first two non-anomalous singleton live births in Missouri (1989-2005). We examined the birthweight distribution and neonatal mortality curves of second births whose elder sibling had low versus adequate/high birthweight. We determined the optimal cut-off point for the classification of low birthweight among infants in each group based on the Youden index. Results: Infants whose elder sibling had low birthweight had a lower mean birthweight and a higher percentage of low birthweight infants versus those whose elder sibling had adequate/high birthweight, but low birthweight infants in the former group had a lower rate of neonatal mortality. Upon standardizing the birthweight distribution to a Z-scale, neonatal mortality rates became comparable between the two groups at every rescaled birthweight for Z-scores >=-3.7. The optimal cut-off point for low birthweight was 2500 and 3000 g among infants whose elder sibling had low and adequate/high birthweight, respectively. Conclusions: Using sibling data for the classification of LBW may enable the identification of average-sized infants who may be at increased risk of neonatal mortality. PMID- 29788354 TI - Antiviral effect of the nucleoside analogue cidofovir in the context of sexual transmission of a gammaherpesvirus in mice. AB - Objectives: To investigate the efficacy of cidofovir to block gammaherpesvirus replication in the context of sexual transmission. Methods: A luciferase expressing strain of murid herpesvirus 4 (MuHV-4) was used to monitor genital virus excretion from infected female BALB/c mice and sexual transmission to naive males. The efficiency of cidofovir to block genital excretion from infected females or replication and host colonization of naive males after sexual contact was tested by treating infected females (either once daily or at a single timepoint), naive males before exposure (either once daily or at a single timepoint) or males 24 h post-exposure. Results: We showed that daily treatment of infected females can reduce MuHV-4 genital shedding by 75%. Similarly, daily preventive treatment of naive males was sufficient to block viral replication and latency establishment in males. In contrast, a single administration of cidofovir to infected females at day 14 post-infection or to naive males 2 to 6 days before contact with MuHV-4-excreting females was not sufficient to significantly reduce viral shedding from females or infection of males, respectively. Interestingly, a single administration of cidofovir to males 24 h after contact with MuHV-4 infected females excreting the virus in the genital tract significantly reduced virus replication in males and seroconversion. Conclusions: Altogether, our results show that cidofovir can significantly reduce gammaherpesvirus replication, excretion and colonization of the naive partner in the context of sexual transmission. Such treatments could therefore be recommended in some specific conditions where gammaherpesvirus infections could be deleterious. PMID- 29788353 TI - Hormonal regulation in adventitious roots and during their emergence under waterlogged conditions in wheat. AB - To gain insights into the molecular mechanisms underlying hormonal regulation in adventitious roots and during their emergence under waterlogged conditions in wheat, the present study investigated transcriptional regulation of genes related to hormone metabolism and transport in the root and stem node tissues. Waterlogging-induced inhibition of axile root elongation and lateral root formation, and promotion of surface adventitious and axile root emergence and aerenchyma formation are associated with enhanced expression levels of ethylene biosynthesis genes, ACS7 and ACO2, in both tissues. Inhibition of axile root elongation is also related to increased root indole acetic acid (IAA) and jasmonate (JA) levels that are associated with up-regulation of specific IAA biosynthesis/transport (TDC, YUC1, and PIN9) and JA metabolism (LOX8, AOS1, AOC1, and JAR1) genes, and transcriptional alteration of gibberellin (GA) metabolism genes (GA3ox2 and GA2ox8). Adventitious root emergence from waterlogged stem nodes is associated with increased levels of IAA and GA but decreased levels of cytokinin and abscisic acid (ABA), which are regulated through the expression of specific IAA biosynthesis/transport (TDC, YUC1, and PIN9), cytokinin metabolism (IPT5-2, LOG1, CKX5, and ZOG2), ABA biosynthesis (NCED1 and NCED2), and GA metabolism (GA3ox2 and GA2ox8) genes. These results enhance our understanding of the molecular mechanisms underlying the adaptive response of wheat to waterlogging. PMID- 29788356 TI - Return-to-Duty Rates Following Minimally Invasive Spine Surgery Performed on Active Duty Military Patients in an Ambulatory Surgery Center. AB - Background: Low back pain is a primary health care utilization driver in the US population. Health care evaluation visits for low back pain are as common as medical evaluation for the common cold. Low back pain is the most common reason for reductions in activities of daily living and work activity in the general population. Although these statistics are compelling, in the military population, there is arguably a significantly greater economic impact on the military population, as the cost to train, retain, and deploy a service member is a tremendous cost. Methods: The current study retrospectively examines surgical outcomes, return to duty, and patient-centric outcomes among 82 active duty or reserve military patients who underwent an outpatient minimally invasive spine surgery Laminotomy Foraminotomy Decompression for the treatment of lumbar spinal stenosis in an ambulatory surgery center. Findings: Overall, our results indicate that within the 82 active duty military service members, 100% of the service members return to duty within 3 mo. Additionally, there was a significant reduction in self-reported pain and disability 12 mo postoperative, whereas the average length of surgery was 62 min with an average estimated blood loss of 30.64 mL. Discussion: The current study indicates that minimally invasive procedures for the treatment of lumbar spinal stenosis in an ambulatory surgery center setting are an effective option for active duty servicemen to reduce return-to-duty rates and symptomatic back-related pain and disability. PMID- 29788355 TI - SWISS-MODEL: homology modelling of protein structures and complexes. AB - Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org. PMID- 29788358 TI - Microbial Signatures as a Predictive Tool in IBD-Pearls and Pitfalls. AB - Studies of microbial signatures have improved our understanding of the role of dysbiosis in gut microbiota for the pathogenesis of inflammatory bowel disease (IBD). New technological advances such as next-generation sequencing facilitate investigations on large patient cohorts, but require methodological considerations regarding study design, sample processing, data analysis, and integration. Here, we summarize recent study approaches in microbial ecology with respect to IBD research and discuss crucial process steps for the production and integration of adequate data sets. PMID- 29788357 TI - Reproductive, Physiological, and Molecular Outcomes in Female Mice Deficient in Dhh and Ihh. AB - Ovarian development requires coordinate communications among oocytes, granulosa cells, and theca cells. Two Hedgehog (Hh) pathway ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), are produced by the granulosa cells and work together to regulate theca cell specification and development. Mice lacking both Dhh and Ihh had loss of normal ovarian function, which raised the question of which biological actions are specifically controlled by each ligand during folliculogenesis. By comparing the reproductive fitness, hormonal profiles, and ovarian transcriptomes among control, Dhh single-knockout (KO), Ihh KO, and Dhh/Ihh double-knockout (DKO) mice, we examined the specific roles of Dhh and Ihh in these processes. Dhh/Ihh DKO female mice were infertile because of a lack of theca cells and their steroid product androgen. Although Dhh and Ihh KO mice were fertile with normal folliculogenesis, they had decreased androgen production and alterations in their ovarian transcriptomes. Absence of Ihh led to aberrant steroidogenesis and elevated inflammation responses, which were not found in Dhh KO mouse ovaries, implicating that IHH has a greater impact than DHH on the activation of the Hh signaling pathway in the ovary. Our findings provide insight into not only how the Hh pathway influences folliculogenesis but also the distinct and overlapping roles of Dhh and Ihh in supporting ovarian development. PMID- 29788360 TI - Use of Social Media for Health-Related Tasks by Adolescents With Inflammatory Bowel Disease: A Step in the Pathway of Transition. AB - Background: Social media is commonly used among the adolescent and young adult population, including those with chronic diseases. For adults, these platforms have been shown to be a major source of health information. Our aims were to explore how youth with inflammatory bowel disease (IBD) use social media for (1) disease information gathering, (2) provider communication, (3) sense of belonging to the IBD community, (4) self-expression around IBD, and (5) disease management/monitoring. Methods: An anonymous and voluntary survey was administered to IBD patients age 12 to 25 years at a single center over 4 months. Results: Of 218 patients approached, there were 109 respondents. The mean age of the cohort (SD) was 18 (2.9) years, 65% were male, and 82% had Crohn's disease. Almost all patients accessed the Internet daily, but only 17% reported looking up information about IBD "always" or "often." Less than half (47%) turned to medical websites (WebMD or Crohn's and Colitis Foundation) for information. A small number (16%) connected with other IBD patients. Patients' preferred communication with provider was by e-mail (88%) compared with a phone call to the office (67%) or hospital website/patient portal (52%). Few patients used mobile applications to monitor symptoms (2%) or for medication reminders (9%), although there was professed interest. Conclusions: Adolescents and young adults with IBD are less likely than adults to use social media for health-related activities. They prefer e-mail rather than oral communication between visits, and privacy seems to be less of a concern. Targeted education and skill building may be helpful for this transitioning population. PMID- 29788361 TI - Treatment of Inflammatory Bowel Disease in the Older Patient. AB - The incidence of inflammatory bowel disease (IBD) is increasing, and as our population ages, there is a growing number of IBD patients who are transitioning into advanced age; 15% to 20% of IBD patients are classified as late-onset (between 60-65 years of age). This has led clinicians to treat a large number of older patients with IBD. The principles of management of IBD in older patients are the same as those who are younger. There are, however, phenotypic differences that are unique to late-onset IBD and age-related concerns that clinicians must consider when initiating therapy for their older patients with IBD. Given the increasing number of older IBD patients, the aim of this article is to present an updated, evidence-based review of the therapeutic options and issues that arise in this unique patient population. PMID- 29788359 TI - Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study. AB - Goal: The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population. Background: IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD. Methods: Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS. Results: Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide 1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls. Conclusions: A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy. PMID- 29788362 TI - Similar Inhibition of Dynamic Adhesion of Lymphocytes From IBD Patients to MAdCAM 1 by Vedolizumab and Etrolizumab-s. AB - Background: Although anti-adhesion therapies are a novel mainstay in the treatment of inflammatory bowel diseases (IBDs), the mechanisms controlling integrin-dependent gut homing are poorly elucidated, and the available techniques for translational functional investigations are limited. Methods: We used dynamic adhesion assays to study adhesion of CD4+ T cells, CD8+ T cells, CD19+ B cells, and granulocytes to the addressins MAdCAM-1, VCAM-1, and ICAM-1. The effects of vedolizumab, natalizumab, etrolizumab-s, anti-CD11a, and anti-CD18 antibodies were explored. Results: Adhesion of peripheral blood leukocytes from IBD patients and control donors could be validly assessed, and integrin-mediated addressin adhesion could be specifically inhibited by anti-integrin antibodies. Numbers of adhering cells were partly, but not completely, related to integrin expression. Vedolizumab and etrolizumab-s resulted in similar reduction of adhesion to MAdCAM 1, and preliminary data proposed an association of dynamic adhesion to MAdCAM-1 with response to vedolizumab therapy. Conclusions: Dynamic adhesion assays are an easy and broadly applicable method for IBD research that is useful for future translational studies and potentially also for supporting clinical treatment decisions. 10.1093/ibd/izy077_video1izy077_Video_15786486962001. PMID- 29788363 TI - Early-Life Military Exposures and Functional Impairment Trajectories Among Older Male Veterans: The Buffering Effect of Psychological Resilience. AB - Objectives: Drawing on the life course framework and theoretical concept of resilience, we examine the impact of early-life service-related exposures (SREs) on later-life functional impairment trajectories among older U.S. male veterans. We conceptualize resilience as a psychological resource potentially moderating the lasting negative consequences of traumatic military exposures. Method: Using the 2013 Veterans Mail Survey linked to the Health and Retirement Study 2006-2014 Leave Behind Questionnaire and RAND Data File (v.N), we estimate latent growth curve models of functional impairment trajectories. Results: SRE to death has a persistent positive effect on functional limitations and activities of daily living limitations. Psychological resilience significantly moderates this association, such that veterans maintaining higher levels of resilience in the face of adverse exposures have considerably less functional impairment over time compared to their counterparts with low levels of resilience. Discussion: Our findings point to the importance of psychological resilience in later life, especially within the realm of traumas occurring in early life. We discuss implications for current military training programs, stressing the importance of research considering individual resources and processes that promote adaptation in the face of adverse life events. PMID- 29788364 TI - Effectiveness of Prenatal Vitamin D Deficiency Screening and Treatment Program: A Stratified Randomized Field Trial. AB - Context: Despite evidence on the association between hypovitaminosis D and adverse pregnancy outcomes and the positive impact of vitamin D supplementation, no evidence exists supporting a universal screening program in pregnancy as part of routine prenatal care. Objective: We sought to determine the effectiveness of a prenatal screening program on optimizing 25-hydroxyvitamin D [25(OH)D] levels and preventing pregnancy complications. Also, to identify a safe regimen, we compared several regimens in a subgroup of vitamin D-deficient pregnant women. Design: Two cities of Masjed-Soleyman and Shushtar from Khuzestan province, Iran, were selected as the screening and nonscreening arms, respectively. Within the screening arm, a randomized controlled trial was conducted on 800 pregnant women. Setting: Health centers of Masjed-Soleyman and Shushtar cities. Patients or Participants: Pregnant women aged 18 to 40 years. Intervention: Women with moderate [25(OH)D, 10 to 20 ng/mL] and severe [25(OH)D, <10 ng/mL] deficiency were randomly divided into four subgroups and received vitamin D3 (D3) until delivery. Main Outcome Measure: Maternal concentration of 25(OH)D at delivery and rate of pregnancy complications. Results: After supplementation, only 2% of the women in the nonscreening site met the sufficiency level (>20 ng/mL) vs 53% of the women in the screening site. Adverse pregnancy outcomes, including preeclampsia, gestational diabetes mellitus, and preterm delivery, were decreased by 60%, 50%, and 40%, respectively, in the screening site. A D3 injection in addition to monthly 50,000 IU maintenance therapy contributed the most to achievement of sufficient levels at delivery. Conclusions: A prenatal vitamin D screening and treatment program is an effective approach in detecting deficient women, improving 25(OH)D levels, and decreasing pregnancy adverse outcomes. PMID- 29788366 TI - Relative household wealth and non-fatal road crashes: analysis of population representative data of Kenyan adults. AB - Background: This study aims to examine potential road crash disparities across relative wealth and location of residence in Kenya by analyzing population representative Demographic and Health Survey data. Methods: Relative wealth was measured by household assets, converted into an index by polychoric principal components analysis. Location and sex-stratified associations between wealth quantiles and crashes were flexibly estimated using fractional polynomial models. Structural equation models were fit to examine whether observed differences may operate through previously identified determinants. Results: In rural areas, crashes were least common for both the poorest men (-5.2 percentage points, 95% CI: -7.3 to -3.2) and women (-1.6 percentage points, 95% CI: -2.9 to -0.4). In urban areas, male crashes were lowest (-3.0 percentage points, 95% CI: -5.2 to 0.8) among the wealthiest, while they peaked in the middle of the female wealth distribution (2.0 percentage points, 95% CI: 0.3-3.8). Male differences operate partially though occupational driving and vehicle ownership. Urban female differences operate partially through household vehicle ownership, but differences for rural women were not explained by modeled determinants. Conclusions: Relative wealth and road crash have opposite associations in rural and urban areas. Especially in rural areas, it is important to mitigate potential unintended effects of economic development. PMID- 29788365 TI - Implementation of different feed withdrawal times and water temperatures in managing turkeys during heat stress. AB - This investigation studied the effects of different feed withdrawal times, water temperatures, and their interaction on growth performance, carcass traits, blood parameters, and health aspects of native turkeys (Egyptian local breed). We distributed native turkey poults (n = 180; 4 wk old) into 3 groups according to feed withdrawal time (ad libitum; feed withdrawal from 800 to 1,400 h, FW8 to 14; and feed withdrawal from 1,400 to 2,000 h, FW14 to 20). Each group was further divided into 2 subgroups corresponding to water temperature (ordinary and chilled water). Our results indicated that birds of FW14 to 20 exhibited the highest (P = 0.0001) body weight (BW) and average daily gain (ADG), whereas turkeys that drank chilled water displayed a higher BW than those that drank ordinary water. Turkeys that were kept under FW8 to 14 and drank chilled water displayed the highest BW at marketing and ADG from 4 to 16 wk of age. The lowest feed conversion ratio (FCR) was exhibited in turkeys kept off feed under the FW14 to 20 regime. Birds that were kept under FW14 to 20 and received chilled water showed the lowest FCR. The meat color scores of the birds that drank chilled water were higher than those that drank ordinary water, whereas birds kept off feed under the FW14 to 20 regime displayed the highest tenderness and juiciness, followed by those fed ad libitum. Turkeys reared under FW14 to 20 exhibited the highest albumin/globulin ratio and glucose content but the lowest globulin and aspartate transaminase (AST) values. Birds that were kept under FW14 to 20 and drank chilled water displayed the lowest corticosterone concentration. Turkeys reared under FW14 to 20 presented the lowest body temperature. Birds that drank chilled water exhibited a lower body temperature than those that drank ordinary water. Turkeys that were fed ad libitum and drank chilled water displayed the lowest body temperature. Conclusively, applying feed withdrawal and cold water had benefits in turkeys during heat stress. Applying these treatments as managerial alternatives for raising native turkeys during the summer season is highly recommended. PMID- 29788368 TI - Pyoderma Gangrenosum: A Review for the Gastroenterologist. AB - Pyoderma gangrenosum (PG) is a rare ulcerative skin disease of unknown etiology often associated with systemic inflammatory conditions, most commonly inflammatory bowel disease (IBD). The most common presentation of PG is spontaneous rapid formation of an extremely painful ulcer on the extremities, associated with significant morbidity and mortality. Rarely, PG can also occur as a chronic peristomal complication or as an acute postoperative complication of a surgical wound. The clinical course is unpredictable; it may not correlate with IBD activity and may even precede a diagnosis of IBD. Pyoderma gangrenosum is a diagnosis of exclusion. Treatment is challenging, often involving a variety of immunosuppressive therapies. This review aims to provide an update for the gastroenterologist on the pathogenesis, presentation, diagnosis, and management of PG, a rare complication of IBD. PMID- 29788367 TI - Infantile Onset Intractable Inflammatory Bowel Disease Due to Novel Heterozygous Mutations in TNFAIP3 (A20). AB - Background: Mutations in tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a key player in the negative feedback regulation of nuclear factor-kappaB signaling, have recently been recognized as leading to early onset autoinflammatory and autoimmune syndrome. Here, we have reported the phenotypes of 3 infantile onset intractable inflammatory bowel disease (IBD) patients with TNFAIP3 mutations and reviewed previously reported cases to establish phenotypic features associated with TNFAIP3 monogenicity. Methods: From January 1, 2015, to December 31, 2017, we recruited 58 infantile-onset IBD patients. Targeted sequencing and whole-exome sequencing were performed. Sanger sequencing confirmed the variants and determined the parental origin. We followed all the patients with TNFAIP3 mutations in our cohort and analyzed their clinical data. Results: Genetic screening in all 58 patients with infantile-onset IBD revealed 44 (75.9%) cases of monogenic disorders, and 3 de novo TNFAIP3 mutations were identified, including 1 nonsense and 2 frame shift mutations. All the mutations resulted in premature stop codon. All 3 patients had multiple systemic involvements, with predominant gastrointestinal diseases. Conclusions: Most infantile-onset IBD was associated with monogenetic mutation, and in addition to the 50 reported genes, other rare genetic variants need to be determined. TNFAIP3 may be an important candidate gene. The treatment of TNFAIP3-associated infantile-onset-IBD was challenging. 10.1093/ibd/izy165_video1izy165.video15789607089001. PMID- 29788369 TI - Searching for Disclosure. PMID- 29788370 TI - Large Traumatic Skull Base Internal Carotid Artery Pseudoaneurysm managed With Endovascular Flow Diversion: 2-Dimensional Operative Video. AB - We present a case of a traumatic skull base internal carotid artery (ICA) pseudoaneurysm treated with endovascular flow diversion stenting. The patient was a 27-year-old male who was involved in a motorcycle accident suffering multiple traumatic injuries including a large skull base fracture that extended through the carotid canal. Computed tomography angiography revealed a 2-cm right ICA pseudoaneurysm. Once the patient was stable, a digital subtraction angiography demonstrated enlargement of the pseudoaneurysm. After his other injuries were addressed by trauma and orthopedic surgery, at day 9 after his initial injury, the patient was loaded with aspirin and clopidrogel in preparation for stent reconstruction of his ICA injury. Under conscious sedation and systemic heparinization, the patient underwent endovascular reconstruction of the large pseudoaneurysm using telescoping flow diversion stents. Immediate intra-aneurysm flow stasis was observed. No procedure-related complications occurred. The patient did well and at last follow-up remained neurologically intact. PMID- 29788371 TI - Selective nanopore sequencing of human BRCA1 by Cas9-assisted targeting of chromosome segments (CATCH). AB - Next generation sequencing (NGS) is challenged by structural and copy number variations larger than the typical read length of several hundred bases. Third generation sequencing platforms such as single-molecule real-time (SMRT) and nanopore sequencing provide longer reads and are able to characterize variations that are undetected in NGS data. Nevertheless, these technologies suffer from inherent low throughput which prohibits deep sequencing at reasonable cost without target enrichment. Here, we optimized Cas9-Assisted Targeting of CHromosome segments (CATCH) for nanopore sequencing of the breast cancer gene BRCA1. A 200 kb target containing the 80 kb BRCA1 gene body and its flanking regions was isolated intact from primary human peripheral blood cells, allowing long-range amplification and long-read nanopore sequencing. The target was enriched 237-fold and sequenced at up to 70* coverage on a single flow-cell. Overall performance and single-nucleotide polymorphism (SNP) calling were directly compared to Illumina sequencing of the same enriched sample, highlighting the benefits of CATCH for targeted sequencing. The CATCH enrichment scheme only requires knowledge of the target flanking sequence for Cas9 cleavage while providing contiguous data across both coding and non-coding sequence and holds promise for characterization of complex disease-related or highly variable genomic regions. PMID- 29788373 TI - Hybrid vigour - poplars play it cool. PMID- 29788372 TI - An active role for neurons in glioma progression: making sense of Scherer's structures. AB - Perineuronal satellitosis, the microanatomical clustering of glioma cells around neurons in the tumor microenvironment, has been recognized as a histopathological hallmark of high-grade gliomas since the seminal observations of Scherer in the 1930s. In this review, we explore the emerging understanding that neuron-glioma cell interactions regulate malignancy and that neuronal activity is a critical determinant of glioma growth and progression. Elucidation of the interplay between normal and malignant neural circuitry is critical to realizing the promise of effective therapies for these seemingly intractable diseases. Here, we review current knowledge regarding the role of neuronal activity in the glioma microenvironment and highlight critical knowledge gaps in this burgeoning research space. PMID- 29788374 TI - Presence of Human Papillomavirus (HPV) Apolipoprotein B Messenger RNA Editing, Catalytic Polypeptide-Like 3 (APOBEC)-Related Minority Variants in HPV-16 Genomes From Anal and Cervical Samples but Not in HPV-52 and HPV-58. AB - Background: The aim of this study was to investigate the presence of minority variants (MVs) in high-risk human papillomavirus (HPV) types (HPV-16, -52, and 58) from cervical and anal smears. Methods: Whole HPV genome ultra-deep sequencing (UDS) was performed on cervical and anal smears collected during patient follow-up. Bioinformatics analyses were performed using Bowtie2 (Geneious). Results: We assessed 55 HPV-16-positive, 20 HPV-52-positive, and 17 HPV-58-positive samples, with significant differences in patient characteristics for the 2 anatomic sites. HPV-16 MVs were detected in 20 samples (36%), with no difference between cervical and anal samples. We did not find an association between the presence of MVs and cytovirological parameters. Seven HPV-16 genomes (13%) were apolipoprotein B messenger RNA editing, catalytic polypeptide-like 3 (APOBEC) edited. Among the cervical HPV-16-positive samples, most MVs (55%) resulted from APOBEC-related mutations. MVs were detected in 10 HPV-52-positive (50%) and 12 HPV-58-positive (71%) samples, with no difference between cervical and anal samples. No APOBEC-related mutations were found on HPV-58 or HPV-52 genomes. Conclusions: Overall, high-risk HPV MVs were found in about half of all cases in both anal and cervical samples. Interestingly, we reported for the first time a differential impact of APOBEC3 mutagenic activity depending on high-risk HPV type. PMID- 29788375 TI - Psychometric evaluation of the Smartphone for Clinical Work Scale to measure nurses' use of smartphones for work purposes. AB - Objective: This study reports the development and psychometric evaluation of the Smartphone for Clinical Work Scale (SCWS) to measure nurses' use of smartphones for work purposes. Methods: Items were developed based on literature review and a preliminary study. After expert consultations and pilot testing, a 20-item scale was administered in January-June 2017 to 517 staff nurses from 19 tertiary-level general hospitals in Metro Manila, Philippines. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate construct validity. Structural equation modeling (SEM) was used to test the predictive validity of SCWS on perceived work productivity. Results: EFA results show that 15 out of 20 items loaded on five factors: communication with clinicians via call and text, communication with doctors via instant messaging, information seeking, communication with nurses via instant messaging, and communication with patients via call and text. CFA results suggest that the five factors that form SCWS have adequate fit to the data, thus supporting construct validity. SEM results suggest predictive validity since SCWS was positively associated with perceived work productivity. Conclusions: The 15-item SCWS showed satisfactory psychometric properties for use in future studies. These studies can focus on identifying factors associated with nurses' use of smartphones for work purposes. PMID- 29788376 TI - The Ocean Gene Atlas: exploring the biogeography of plankton genes online. AB - The Ocean Gene Atlas is a web service to explore the biogeography of genes from marine planktonic organisms. It allows users to query protein or nucleotide sequences against global ocean reference gene catalogs. With just one click, the abundance and location of target sequences are visualized on world maps as well as their taxonomic distribution. Interactive results panels allow for adjusting cutoffs for alignment quality and displaying the abundances of genes in the context of environmental features (temperature, nutrients, etc.) measured at the time of sampling. The ease of use enables non-bioinformaticians to explore quantitative and contextualized information on genes of interest in the global ocean ecosystem. Currently the Ocean Gene Atlas is deployed with (i) the Ocean Microbial Reference Gene Catalog (OM-RGC) comprising 40 million non-redundant mostly prokaryotic gene sequences associated with both Tara Oceans and Global Ocean Sampling (GOS) gene abundances and (ii) the Marine Atlas of Tara Ocean Unigenes (MATOU) composed of >116 million eukaryote unigenes. Additional datasets will be added upon availability of further marine environmental datasets that provide the required complement of sequence assemblies, raw reads and contextual environmental parameters. Ocean Gene Atlas is a freely-available web service at: http://tara-oceans.mio.osupytheas.fr/ocean-gene-atlas/. PMID- 29788378 TI - Laboratory Validation and Field Assessment of Petroleum Laboratory Technicians' Dermal Exposure to Crude Oil Using a Wipe Sampling Method. AB - Crude oil may cause adverse dermal effects therefore dermal exposure is an exposure route of concern. Galea et al. (2014b) reported on a study comparing recovery (wipe) and interception (cotton glove) dermal sampling methods. The authors concluded that both methods were suitable for assessing dermal exposure to oil-based drilling fluids and crude oil but that glove samplers may overestimate the amount of fluid transferred to the skin. We describe a study which aimed to further evaluate the wipe sampling method to assess dermal exposure to crude oil, with this assessment including extended sample storage periods and sampling efficiency tests being undertaken at environmental conditions to mimic those typical of outdoor conditions in Saudi Arabia. The wipe sampling method was then used to assess the laboratory technicians' actual exposure to crude oil during typical petroleum laboratory tasks. Overall, acceptable storage efficiencies up to 54 days were reported with results suggesting storage stability over time. Sampling efficiencies were also reported to be satisfactory at both ambient and elevated temperature and relative humidity environmental conditions for surrogate skin spiked with known masses of crude oil and left up to 4 h prior to wiping, though there was an indication of reduced sampling efficiency over time. Nineteen petroleum laboratory technicians provided a total of 35 pre- and 35 post-activity paired hand wipe samples. Ninety-three percent of the pre-exposure paired hand wipes were less than the analytical limit of detection (LOD), whereas 46% of the post-activity paired hand wipes were less than the LOD. The geometric mean paired post-activity wipe sample measurement was 3.09 ug cm-2 (range 1.76-35.4 ug cm-2). It was considered that dermal exposure most frequently occurred through direct contact with the crude oil (emission) or via deposition. The findings of this study suggest that the wipe sampling method is satisfactory in quantifying laboratory technicians' dermal exposure to crude oil. It is therefore considered that this wipe sampling method may be suitable to quantify dermal exposure to crude oil for other petroleum workers. PMID- 29788377 TI - WEGO 2.0: a web tool for analyzing and plotting GO annotations, 2018 update. AB - WEGO (Web Gene Ontology Annotation Plot), created in 2006, is a simple but useful tool for visualizing, comparing and plotting GO (Gene Ontology) annotation results. Owing largely to the rapid development of high-throughput sequencing and the increasing acceptance of GO, WEGO has benefitted from outstanding performance regarding the number of users and citations in recent years, which motivated us to update to version 2.0. WEGO uses the GO annotation results as input. Based on GO's standardized DAG (Directed Acyclic Graph) structured vocabulary system, the number of genes corresponding to each GO ID is calculated and shown in a graphical format. WEGO 2.0 updates have targeted four aspects, aiming to provide a more efficient and up-to-date approach for comparative genomic analyses. First, the number of input files, previously limited to three, is now unlimited, allowing WEGO to analyze multiple datasets. Also added in this version are the reference datasets of nine model species that can be adopted as baselines in genomic comparative analyses. Furthermore, in the analyzing processes each Chi square test is carried out for multiple datasets instead of every two samples. At last, WEGO 2.0 provides an additional output graph along with the traditional WEGO histogram, displaying the sorted P-values of GO terms and indicating their significant differences. At the same time, WEGO 2.0 features an entirely new user interface. WEGO is available for free at http://wego.genomics.org.cn. PMID- 29788380 TI - Good intentions are not enough: how informatics interventions can worsen inequality. AB - Health informatics interventions are designed to help people avoid, recover from, or cope with disease and disability, or to improve the quality and safety of healthcare. Unfortunately, they pose a risk of producing intervention-generated inequalities (IGI) by disproportionately benefiting more advantaged people. In this perspective paper, we discuss characteristics of health-related interventions known to produce IGI, explain why health informatics interventions are particularly vulnerable to this phenomenon, and describe safeguards that can be implemented to improve health equity. We provide examples in which health informatics interventions produced inequality because they were more accessible to, heavily used by, adhered to, or effective for those from socioeconomically advantaged groups. We provide a brief outline of precautions that intervention developers and implementers can take to guard against creating or worsening inequality through health informatics. We conclude by discussing evaluation approaches that will ensure that IGIs are recognized and studied. PMID- 29788381 TI - The Role of Apathy and Depression on Verbal Learning and Memory Performance After Stroke. AB - Objective: Psychiatric symptoms, including depression and apathy, may significantly impede functional and cognitive capabilities following a cerebrovascular event. This study examined the role of apathy and depression on learning and memory performance in stroke patients. Method: Stroke patients (n = 140 [119 ischemic, 21 hemorrhagic], mean age = 60.6 [SD = 15.1]) completed the Apathy Evaluation Scale (AES), the Center for Epidemiologic Studies Depression Scale (CES-D), and the California Verbal Learning Test-Second Edition (CVLT-II). Results: Using a 2 * 2 MANOVA with depression (CESD >= 16) and apathy (AES >= 34) as the independent variables and cognitive performance (i.e., verbal acquisition, short-term free recall, and long-term free recall) as the dependent variables, we found a main effect for apathy (F[3,134] = 2.98, p = .034), such that apathetic stroke patients (n = 24) performed significantly worse on verbal acquisition (F[1,136] = 6.44; p = .012), short-term free recall (F[1,136] = 7.86; p = .006), and long-term free recall (F[1,136] = 8.37; p = .004) than nonapathetic stroke patients (n = 116). There was no main effect of depression on cognitive performance (F[1,136] = 1.72, p = .155). Conclusions: These results suggest that apathy, not depression, is related to verbal memory performance in stroke patients. Future research should explore whether treatment of apathy (e.g., improving motivation) could be a novel target for improving cognition after stroke. Researchers should also examine whether this model can be applied to other aspects of cognition, including executive function and other areas of memory including autobiographical and working memory. PMID- 29788382 TI - Colonic Inhibition of Phosphatase and Tensin Homolog Increases Colitogenic Bacteria, Causing Development of Colitis in Il10-/- Mice. AB - Background: Phosphatase and tensin homolog (Pten) is capable of mediating microbe induced immune responses in the gut. Thus, Pten deficiency in the intestine accelerates colitis development in Il10-/- mice. As some ambient pollutants inhibit Pten function and exposure to ambient pollutants may increase inflammatory bowel disease (IBD) incidence, it is of interest to examine how Pten inhibition could affect colitis development in genetically susceptible hosts. Methods: With human colonic mucosa biopsies from pediatric ulcerative colitis and non-IBD control subjects, we assessed the mRNA levels of the PTEN gene and the gene involved in IL10 responses. The data from the human tissues were corroborated by treating Il10-/-, Il10rb-/-, and wild-type C57BL/6 mice with Pten specific inhibitor VO-OHpic. We evaluated the severity of mouse colitis by investigating the tissue histology and cytokine production. The gut microbiome was investigated by analyzing the 16S ribosomal RNA gene sequence with mouse fecal samples. Results: PTEN and IL10RB mRNA levels were reduced in the human colonic mucosa of pediatric ulcerative colitis compared with non-IBD subjects. Intracolonic treatment of the Pten inhibitor induced colitis in Il10-/- mice, characterized by reduced body weight, marked colonic damage, and increased production of inflammatory cytokines, whereas Il10rb-/- and wild-type C57BL/6 mice treated with the inhibitor did not develop colitis. Pten inhibitor treatment changed the fecal microbiome, with increased abundance of colitogenic bacteria Bacteroides and Akkermansia in Il10-/- mice. Conclusions: Loss of Pten function increases the levels of colitogenic bacteria in the gut, thereby inducing deleterious colitis in an Il10-deficient condition. PMID- 29788379 TI - DNA Damage Response and Repair, DNA Methylation, and Cell Death in Human Neurons and Experimental Animal Neurons Are Different. AB - Neurological disorders affecting individuals in infancy to old age elude interventions for meaningful protection against neurodegeneration, and preclinical work has not translated to humans. We studied human neuron responses to injury and death stimuli compared to those of animal neurons in culture under similar settings of insult (excitotoxicity, oxidative stress, and DNA damage). Human neurons were differentiated from a cortical neuron cell line and the embryonic stem cell-derived H9 line. Mouse neurons were differentiated from forebrain neural stem cells and embryonic cerebral cortex; pig neurons were derived from forebrain neural stem cells. Mitochondrial morphology was different in human and mouse neurons. Human and mouse neurons challenged with DNA-damaging agent camptothecin showed different chromatin condensation, cell death, and DNA damage sensor activation. DNA damage accumulation and repair kinetics differed among human, mouse, and pig neurons. Promoter CpG island methylation microarrays showed significant differential DNA methylation in human and mouse neurons after injury. Therefore, DNA damage response, DNA repair, DNA methylation, and autonomous cell death mechanisms in human neurons and experimental animal neurons are different. PMID- 29788383 TI - Assessment of Quality of Life in Chinese Patients With Inflammatory Bowel Disease and their Caregivers. AB - Background: Chronic diseases such as inflammatory bowel disease (IBD) usually affect the psychological status and health-related quality of life (HRQOL) of patients and their caregivers. The aim of this study was to evaluate the level of anxiety, depression, and HRQOL and find the risk factors predictive of HRQOL in IBD patients and their caregivers in a Chinese population. Methods: One hundred four adult patients with IBD, 102 family caregivers, and 99 healthy controls were enrolled. They completed self-administered surveys related to QOL and psychological questionnaires, including the Short Inflammatory Bowel Disease Questionnaire (patients only), the Short Form-36 Health Survey (SF-36), Self rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Results: Both the mean SAS total score and the mean SDS total score among the patients and the caregivers were found to be significantly higher than those among the general population (P < 0.05). Total SF-36 score was significantly different between the patients and the general population (P = 0.001), and between caregivers and the general population (P = 0.011). The result showed that the total SF-36 score of the patients had a significant negative correlation with SAS score in the patients (P = 0.040), SDS score in the patients (P = 0.004), annual income (P = 0.036), use of biologicals (P = 0.028), frequency of hospitalization in the last year (P = 0.033), and severity of IBD (P = 0.021). The total SF-36 score of the caregivers was significantly and negatively correlated with SDS score in the caregivers (P = 0.010), SDS score in the patients (P = 0.010), use of biologicals (P = 0.013), and frequency of hospitalization in the last year (P = 0.010) of the patients. Conclusions: A large proportion of IBD patients and their caregivers experience a high level of anxiety and depression and an impaired HRQOL. Higher levels of anxiety and depression, annual income, use of biologicals, higher frequency of hospitalization in the last year, and disease activity were independent predictors of reduced patient HRQOL; higher levels of depression in both caregivers and patients, use of biologicals, and frequency of hospitalization in the last year of the patients were independent predictors of reduced caregiver HRQOL. PMID- 29788384 TI - Time-to-Event Modeling of Left- or Right-Censored Toxicity Data in Nonclinical Drug Toxicology. AB - A time-to-event (TTE) model has been developed to characterize a histopathology toxicity that can only be detected at the time of animal sacrifice. The model of choice was a hazard model with a Weibull distribution and dose was a significant covariate. The diagnostic plots showed a satisfactory fit of the data, despite the high degree of left and right censoring. Comparison to a probabilistic logit model shows similar performance in describing the data with a slight underestimation of survival by the Logit model. However, the TTE model was found to be more predictive in extrapolating toxicity risk beyond the observation range of a truncated dataset. The diagnostic and comparison outcomes would suggest using the TTE approach as a first choice for characterizing short and long-term risk from nonclinical toxicity studies. However, further investigations are needed to explore the domain of application of this kind of approach in drug safety assessment. PMID- 29788387 TI - Methodological Issues on the Accuracy and Precision of Clinical Examination in the Diagnosis of Myofascial Pain Syndrome. PMID- 29788385 TI - Systematic Review and Meta-analysis: Vedolizumab and Postoperative Complications in Inflammatory Bowel Disease. AB - Background: Several studies have reported the surgical outcomes of inflammatory bowel disease (IBD) patients exposed to vedolizumab (VDZ) preoperatively, with conflicting results. This meta-analysis aims to evaluate the risk of postoperative complications in IBD patients preoperatively exposed to VDZ in comparison with patients exposed to anti-tumor necrosis factor (anti-TNF) treatment or no biologic therapy. Methods: A systematic review with a meta analysis of the existing literature was conducted. The main outcomes included the odds of developing overall postoperative complications, infectious complications, surgical site infections, need for repeat surgery, and major postoperative complications, as defined by the Clavien-Dindo criteria. Results: Four studies were included in the meta-analysis. The risk of all postoperative complications was not significantly different between IBD patients exposed preoperatively to VDZ vs anti-TNFs (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.21 1.88). In patients with ulcerative colitis (UC), the OR for complications was significantly lower in VDZ-exposed as opposed to anti-TNF-exposed patients (OR, 0.35; 95% CI, 0.14-0.85); the comparison was insignificant in Crohn's disease. There were no significant differences in the risk of infectious complications, surgical site infections, need for reoperation, or major surgical complications in patients exposed to VDZ vs anti-TNFs. There were no significant differences in outcomes when comparing patients exposed to VDZ with those not given biologic therapy. Conclusions: This meta-analysis did not detect an increased risk of postoperative complications with preoperative VDZ exposure; the risk of overall complications may be lower in UC patients in comparison with those with anti-TNF exposure. These results merit further verification in future studies. PMID- 29788386 TI - Diversity, not uniformity: slaughter and electrical waterbath stunning procedures in Belgian slaughterhouses. AB - Data on slaughter and stunning protocols in Belgian poultry abattoirs were collected, and subsequently the survival rate after electrical waterbath stunning in 1,400 animals across 7 selected slaughterhouses was determined. The majority of the abattoirs applied electrical waterbath stunning (72%), whereas the other methods were gas stunning (13%), head-only stunning (6%), and dry stunning (3%). In 6% of the slaughterhouses, the birds were killed without previous stunning, according to religious rites (i.e., ritual or religious slaughter). Although religious slaughter occurred in a substantial number of abattoirs, the customers of the majority of them allowed stunning, provided the animals were not killed by the stunning procedure. Substantial variation both in electrical waterbath devices and technical settings (electrical current type, wave type, voltage, frequency) combinations was observed. These settings did not only differ between slaughterhouses, but also between subsequent visits to the same slaughterhouse. Despite this variation, all systems comprised a constant voltage, multiple bird stunner. The minimum average electrical current that every chicken should receive at a certain frequency, as stated by the European Regulation No 1099/2009, was not achieved for each animal monitored due to the bird's characteristics and the different applied stunning settings, with the exception of all ISA laying hens and broiler breeders in one particular slaughterhouse. The survival rate ranged from 96.0 to 100%, 97.0 to 100%, 68.0%, 72.0 to 85.1%, and 5.6 to 52.4% in 5-wk old broilers, 6-wk-old broilers, LSL laying hens, ISA laying hens, and broiler breeders, respectively. Monitoring of unconsciousness after passing through the waterbath was not always performed and when it was, there was no uniformity in the applied criteria. It was concluded that a large variation in slaughter and stunning practices exists among slaughterhouses in Belgium. Further research should explore the effect of the different settings on inducing a successful stun and on carcass quality, and assess if the observed variation also exists in other EU member states. PMID- 29788388 TI - Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage. AB - BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery. OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation. METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery. RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 +/- 20 vs 40.6 +/- 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery. CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone. PMID- 29788389 TI - Pregnancy after vasectomy: surgical reversal or assisted reproduction? AB - STUDY QUESTION: Should we opt for surgical vasovasostomy or IVF/ICSI after a vasectomy? SUMMARY ANSWER: Both options reveal acceptable pregnancy rates though the time to pregnancy was significantly lower in the immediate IVF/ICSI group. WHAT IS KNOWN ALREADY: About 7.4% of men regret their vasectomy and express a renewed child wish. The choice between surgical vasectomy reversal or ICSI remains difficult for patients and their fertility specialist. STUDY DESIGN, SIZE, DURATION: This study was a retrospective single-center cohort analysis of all males with a vasectomy in the past seeking treatment between 2006 and 2011 (n = 163). One group of patients opted for a reanastomosis procedure while the others opted for an immediate IVF/ICSI treatment. This included 99 males who underwent reanastomosis and 64 couples who immediately underwent ICSI treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All reanastomosis procedures were done by the same surgeon. ICSI was used in all cases where testicular sperm were extracted by fine needle aspiration (FNA) or testicular sperm extraction (TESE). MAIN RESULTS AND THE ROLE OF CHANCE: The mean male age at vasectomy was 35.5 years and 44.4 years at reanastomosis. The mean (range) obstructive interval was 9.53 years (1-27). No significant differences were found between the two groups in female patient characteristics, such as age and parity. In the reversal group, the crude cumulative delivery rate (CDR) was 49.5%. However, in the 45 patients of this group who attempted to conceive spontaneously ('primary reanastomosis' pathway), the crude CDR was 40.0%. The remaining 54 patients (the 'switchers' pathway) who underwent a reversal procedure and later switched to ART, had a crude CDR of 57.4%. Of these, four patients opted for insemination, including two who later decided to switch to IVF/ICSI. The 64 patients who immediately underwent IVF/ICSI ('primary IVF/ICSI' pathway) had a crude CDR of 43.8% and an expected CDR of 51.6%. The difference in delivery rates between the primary reanastomosis group (40.0%) and the primary IVF/ICSI group (43.8%) was not statistically significant. Time to pregnancy was significantly shorter in the primary IVF/ICSI pathway, at 8.2 versus 16.3 months in the reanastomosis group. LIMITATIONS, REASONS FOR CAUTION: The study population was rather small. Furthermore, the study may be limited by the fact that the reason for the renewed child wish in most cases was a new relationship with another woman, a factor which may also play a role in the cause of infertility. WIDER IMPLICATIONS OF THE FINDINGS: Recanalisation of the vas seems to be a reasonable alternative for patients who do not wish to undergo immediate IVF/ICSI. In those who opt for ART immediately, the cumulative pregnancy rates seem comparable but the pregnancies occurred earlier. STUDY FUNDING, COMPETING INTEREST(S): No funding was used for this study. There is no conflict of interest for this study. TRIAL REGISTRATION NUMBER: N/A. PMID- 29788391 TI - Distinct Histopathologic and Molecular Alterations in Inflammatory Bowel Disease Associated Intestinal Adenocarcinoma: c-MYC Amplification is Common and Associated with Mucinous/Signet Ring Cell Differentiation. AB - Background: Chronic idiopathic inflammatory bowel disease (IBD) is a significant risk factor for the development of intestinal adenocarcinoma. The underlying molecular alterations in IBD-associated intestinal adenocarcinoma remain largely unknown. Methods: We compared the clinicopathologic and molecular features of 35 patients with 47 IBD-associated intestinal adenocarcinomas with a consecutive series of 451 patients with sporadic colorectal carcinoma identified at our institution and published data on sporadic colorectal carcinoma. Results: c-MYC amplification was the most frequent molecular alteration identified in 33% of IBD associated intestinal adenocarcinoma that is a significantly higher frequency than in sporadic colorectal carcinoma (8%) (P = 0.0001). Compared to sporadic colorectal carcinoma, IBD-associated intestinal adenocarcinomas more frequently demonstrated mucinous differentiation (60% vs 25%, P < 0.001) and signet ring cell differentiation (28% vs 4%, P < 0.001). Mucinous and signet ring cell differentiation were significantly associated with the presence of c-MYC amplification (both with P < 0.05). HER2 positivity (11%), KRAS exon 2 or 3 mutation (10%), and IDH1 mutation (7%) were less commonly observed in IBD associated intestinal adenocarcinoma. There was an association between poor survival and HER2 status with 3 of 4 patients having HER2-positive adenocarcinoma dead of disease at last clinical follow-up; however, no statistically significant survival effect was identified for any of the molecular alterations identified. Conclusions: We demonstrate that IBD-associated intestinal adenocarcinomas have a high frequency of c-MYC amplification that is associated with mucinous and signet ring cell differentiation. Many of the identified molecular alterations have potential therapeutic relevance, including HER2 amplification, IDH1 mutation, and low frequency KRAS mutation. PMID- 29788392 TI - Prognostic accuracy of different lymph node staging systems in rectal adenocarcinoma with or without preoperative radiation therapy. AB - Background and objective: A variety of different lymph node (LN) staging systems have been developed to describe the lymph node status accurately. We aim to compare the prognostic accuracy of American Joint Committee on Cancer seventh N stage relative to negative number of lymph node (nLN), lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) in rectal adenocarcinoma (RC). Methods: A total of 19 167 Stage II-III rectal cancer patients who underwent surgical resection of rectal adenocarcinoma were identified from Surveillance, Epidemiology and End Results database. Akaike's Information Criterion (AIC) and the Harrell's concordance index (c statistic) were used to evaluate the relative discriminative power of the different LN staging systems. Results: Of the 19 167 patients, 10 958 received preoperative radiotherapy (pre-RT cohort) and 8209 patients were treated with surgical resection directly (SURG cohort). When assessed using categorical cutoff values, LNR has a somewhat better prognostic accuracy both in pre-RT (c-index: 0.62; AIC: 2988.6) and SURG groups (c-index: 0.60; AIC: 3359.8). Further analysis based on different total number of lymph node (TNLN) suggested that when less than 10 lymph nodes were retrieved, LNR exhibited significant superiority (pre-RT: c-index: 0.597, AIC: 1006.8; SURG: c index: 0.560, AIC: 810.5). When analyzed as a continuous variable, the LODDS system performed the best and was not impacted by TNLN. Conclusion: When assessed as a categorical variable, LNR was the most powerful method to predict survival for Stage II-III RC patients with limited TNLN. Rather, LODDS was the most accurate staging system regardless of the TNLN when LN status was modeled as continuous variable. PMID- 29788393 TI - Epidemiology of Symptomatic Chiari Malformation in Tatarstan: Regional and Ethnic Differences in Prevalence. AB - BACKGROUND: Epidemiology can assess the effect of Chiari I malformation (CM1) on the neurological health of a population and evaluate factors influencing CM1 development. OBJECTIVE: To analyze the regional and ethnic differences in the prevalence of CM1. METHODS: The population of the Republic of Tatarstan (RT) in the Russian Federation was evaluated for patients with CM1 symptoms over an 11-yr period. Typical symptoms of CM1 were found in 868 patients. Data from neurological examination and magnetic resonance imaging (MRI) measurement of posterior cranial fossa structures were analyzed. RESULTS: MRI evidence of CM1, defined as cerebellar tonsils lying at least 5 mm inferior to the foramen magnum, was found in 67% of symptomatic patients. Another 33% of symptomatic patients had 2 to 4 mm of tonsillar ectopia, which we defined as "borderline Chiari malformation type 1 (bCM1)." The period prevalence in the entire RT for symptomatic CM1 was 20:100 000; for bCM1 was 10:100 000; and for CM1 and bCM1 together was 30:100 000. Prevalence of patients with CM1 symptoms was greater in the northern than southern districts of Tatarstan, due to a high prevalence (413:100 000) of CM1 in the Baltasy region in one of the northern districts. CONCLUSION: One-third of patients with typical symptoms of CM1 had less than 5 mm of tonsillar ectopia (bCM1). Assessments of the health impact of CM1-type symptoms on a patient population should include the bCM1 patient group. A regional disease cluster of patients with Chiari malformation was found in Baltasy district of RT and needs further study. PMID- 29788390 TI - Cognitive Performance as Predictor and Outcome of Adolescent Bariatric Surgery: A Nonrandomized Pilot Study. AB - Objectives: Evidence in adults suggests that improvements in cognitive performance may follow weight loss resulting from bariatric surgery, and baseline cognitive performance may be associated with weight loss following surgery. This has not been evaluated in adolescents. Method: Participants were 38 adolescents of age 14-21 years composed of three groups: (1) 12 adolescents with severe obesity who received vertical sleeve gastrectomy during the study (VSG); (2) 14 adolescents with severe obesity who were wait-listed for VSG (WL); and (3) 12 healthy weight controls (HC). Participants completed testing of visual memory, verbal memory, and executive functioning at baseline (T1), which occurred presurgery for the VSG group, and approximately 4 months after baseline (T2). Body mass index (BMI) was assessed at T1, T2, and additionally at 6 months following VSG for the adolescents who received surgery. Results: Although there was evidence of greater improvement for the VSG as compared with WL and HC groups in visual and verbal memory, group differences did not reach significance and effect sizes were small (eta2 < 0.01). There was a significant positive association between indices of baseline executive functioning and excess BMI loss at 6 months postsurgery. Conclusions: This small pilot study showed no significant differences by group in cognitive performance post-VSG. There was a significant association of baseline cognitive performance with weight loss outcomes. Given the very preliminary nature of these results in a small sample, future research should examine these relationships in a larger sample and evaluate mechanisms of these associations (e.g., insulin resistance, sleep, physical activity). PMID- 29788395 TI - Psychological Functioning in Patients with Chronic Obstructive Pulmonary Disease: A Preliminary Study of Relations with Smoking Status and Disease Impact. AB - Introduction: Chronic obstructive pulmonary disease (COPD) is a tobacco-related disease associated with several comorbid conditions, including elevated rates of depression and anxiety. Psychological factors that commonly underlie nicotine dependence, depression, and anxiety may represent novel treatment targets, but have not yet been examined among COPD patients. We assessed three psychological factors - anxiety sensitivity (AS; fear of anxiety-related sensations), distress intolerance (DI; inability to withstand distressing states), and anhedonia (Anh; diminished sense of pleasure or interest) - in relation to smoking status, COPD symptom impact, and negative response to COPD symptoms. Methods: We conducted a single-session laboratory assessment with 37 COPD patients (17 current daily smokers and 20 former smokers). All participants completed self-report measures of psychological factors, COPD symptom impact, response to COPD symptoms, and anxiety and depression symptoms. Results: Current vs. former smokers with COPD reported higher levels of AS, DI, and Anh. In univariate regression models, AS, DI, and Anh were each associated with greater COPD symptom impact and breathlessness catastrophizing. Only AS remained a significant predictor of COPD symptom impact and breathlessness catastrophizing after adjusting for general depression and anxiety symptoms. Conclusions: Our preliminary study is the first to assess AS, DI, and Anh among COPD patients. These psychological factors were elevated among current smokers and associated with more negative disease impact, suggesting their potential utility as treatment targets within this clinical population. Implications: While elevated rates of anxiety and depression among COPD patients have been well-characterized, few studies have specifically addressed the causal, modifiable psychological factors that may underlie these disorders. Our preliminary findings demonstrate associations of three psychological factors - anxiety sensitivity, distress intolerance, and anhedonia with smoking status, COPD symptom impact, and negative reaction to symptoms. Cognitive-behavioral interventions targeted to these psychological factors may improve smoking cessation outcomes and disease adjustment among COPD patients. PMID- 29788394 TI - RNA Interference of the Muscle Actin Gene in Bed Bugs: Exploring Injection Versus Topical Application for dsRNA Delivery. AB - Bed bugs are one the most troublesome household pests that feed primarily on human blood. RNA interference (RNAi) is currently being pursued as a potential tool for insect population management and has shown efficacy against some phytophagous insects. We evaluated the different techniques to deliver dsRNA specific to bed bug muscle actin (dsactin) into bed bugs. Initially, stability of dsRNA in human blood was studied to evaluate the feasibility of feeding method. Adult bed bugs were injected with dsRNA between last thoracic segment and first abdominal segment on the ventral side, with a dose of 0.2 ug dsactin per insect. In addition to injection, dsactin was mixed in acetone and treated topically in the abdomens of fifth stage nymphs. We found the quick degradation of dsRNA in blood. Injection of dsactin caused significant depletion of actin transcripts and substantial reduction in oviposition and lethality in female adults. Topically treated dsRNA in fifth stage nymphs had no effect on actin mRNA expression and survival. Our results demonstrated that injection is a reliable method of dsRNA delivery into bed bugs while topical treatment was not successful. This research provides an understanding on effective delivery methods of dsRNA into bed bugs for functional genomics research and feasibility of the RNAi based molecules for pest management purposes. PMID- 29788396 TI - Injury Surveillance and Reporting for Trainees with Bone Stress Injury: Current Practices and Recommendations. AB - Background: Musculoskeletal injuries, including lower extremity bone stress injuries (BSI) significantly impact initial entry training (IET) in the U.S. Army due to limited duty days, trainee attrition, early medical discharge, and related financial costs. Factors complicating trainee BSI surveillance include inconsistent BSI coding practices, attrition documentation as both administrative separations and medical discharges and the inability to code for BSI grade or severity when using International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) codes. Methods: A multidisciplinary expert panel developed policy guidance to enhance clinical and administrative management of BSI, following extensive analysis of current, peer reviewed literature. Policy guidance incorporates leading practices concerning clinical BSI management, including imaging procedures, recommended notifications, early intervention, and ICD-10 diagnostic coding procedures. Policy guidance also standardizes BSI grading criteria for magnetic resonance imaging and skeletal scintigraphy (bone scan). Findings: Multidisciplinary expert opinion indicates inconsistent BSI diagnosis and management across IET due to variability in trainee BSI grading, documentation, and coding practices. Injury surveillance conducted by the United States Army Medical Command (USAMEDCOM) will benefit from routine, standardized musculoskeletal injury data base searches by BSI severity/grade and anatomical location upon implementation of BSI policy guidance. Discussion: Effective injury surveillance is critical for determining trainee BSI incidence and attrition, developing anticipated return to duty (RTD) timelines, and assessing long-term outcomes. BSI RTD timelines should account for gender, BSI grade/severity, anatomical location, and type of intervention. Well defined RTD timelines would benefit administrative decision-making purposes, including whether to grant convalescent leave or enroll in the Warrior Training and Rehabilitation Program during BSI recovery. Enhanced management procedures may improve initial enlistment completion rates for trainees sustaining at least one BSI who eventually complete IET. PMID- 29788398 TI - Inferring Diversification Rate Variation From Phylogenies With Fossils. AB - Time-calibrated phylogenies of living species have been widely used to study the tempo and mode of species diversification. However, it is increasingly clear that inferences about species diversification - extinction rates in particular - can be unreliable in the absence of paleontological data. We introduce a general framework based on the fossilized birth-death process for studying speciation extinction dynamics on phylogenies of extant and extinct species. The model assumes that phylogenies can be modeled as a mixture of distinct evolutionary rate regimes and that a hierarchical Poisson process governs the number of such rate regimes across a tree. We implemented the model in BAMM, a computational framework that uses reversible jump Markov chain Monte Carlo to simulate a posterior distribution of macroevolutionary rate regimes conditional on the branching times and topology of a phylogeny. The implementation we describe can be applied to paleontological phylogenies, neontological phylogenies, and to phylogenies that include both extant and extinct taxa. We evaluate performance of the model on datasets simulated under a range of diversification scenarios. We find that speciation rates are reliably inferred in the absence of paleontological data. However, the inclusion of fossil observations substantially increases the accuracy of extinction rate estimates. We demonstrate that inferences are relatively robust to at least some violations of model assumptions, including heterogeneity in preservation rates and misspecification of the number of occurrences in paleontological datasets. PMID- 29788397 TI - Polyspecific Intravenous Immunoglobulin in Clindamycin-treated Patients With Streptococcal Toxic Shock Syndrome: A Systematic Review and Meta-analysis. AB - We evaluated the effect of intravenous immunoglobulin (IVIG) on mortality in clindamycin-treated streptococcal toxic shock syndrome using a meta-analysis. In association with IVIG, mortality fell from 33.7% to 15.7% with remarkable consistency across the single randomized and four nonrandomized studies. PMID- 29788399 TI - Reply to 'Travellers' diarrhoea in children: a blind spot in the expert panel guidelines on prevention and treatment'. PMID- 29788400 TI - Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study. AB - Trip Doctor(r), a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale. PMID- 29788402 TI - Internationally adopted children: not only infectious diseases! AB - Information on prevalence of special needs in internationally adopted children (IAC) is incomplete. We reviewed data from 422 IAC screened at a single Centre in Italy in 2015-16. Prevalence of special needs reached 17.1% (n = 72). Among these children, the most frequent conditions were fetal alcohol spectrum disorders (FASD; n = 30; 7.1%), cleft lip palate (n = 8; 1.9%) and other congenital malformations (n = 20; 4.7%). Worrisomely, 25 out of 52 (48.1%) Russian children presented with FASD. PMID- 29788401 TI - Enabling clinicians to easily find location-based travel health recommendations is innovation needed? AB - Background: The types of place names and the level of geographic detail that patients report to clinicians regarding their intended travel itineraries vary. The reported place names may not match those in published travel health recommendations, making traveler-specific recommendations potentially difficult and time-consuming to identify. Most published recommendations are at the country level; however, subnational recommendations exist when documented disease risk varies within a country, as for malaria and yellow fever. Knowing the types of place names reported during consultations would be valuable for developing more efficient ways of searching and identifying recommendations, hence we inventoried these descriptors and identified patterns in their usage. Methods: The data analyzed were previously collected individual travel itineraries from pretravel consultations performed at Global TravEpiNet (GTEN) travel clinic sites. We selected a clinic-stratified random sample of records from 18 GTEN clinics that contained responses to an open-ended question describing itineraries. We extracted and classified place names into nine types and analyzed patterns relative to common travel-related demographic variables. Results: From the 1756 itineraries sampled, 1570 (89%) included one or more place names, totaling 3366 place names. The frequency of different types of place names varied considerably: 2119 (63%) populated place, 336 (10%) tourist destination, 283 (8%) physical geographic area, 206 (6%) vague subnational area, 163 (5%) state, 153 (5%) country, 48 (1%) county, 12 (1%) undefined. Conclusions: The types of place names used by travelers to describe travel itineraries during pretravel consultations were often different from the ones referenced in travel health recommendations. This discrepancy means that clinicians must use additional maps, atlases or online search tools to cross-reference the place names given to the available recommendations. Developing new clinical tools that use geographic information systems technology would make it easier and faster for clinicians to find applicable recommendations for travelers. PMID- 29788404 TI - Snakemake-a scalable bioinformatics workflow engine. PMID- 29788403 TI - Evaluating Previous Antibiotic Use as a Risk Factor for Acute Gastroenteritis Among Children in Davidson County, Tennessee, 2014-2015. AB - Background: Epidemiologic studies that evaluate the relationship between previous antibiotic use and acute gastroenteritis (AGE) in the pediatric population are currently lacking. Methods: We analyzed inpatient and outpatient children with AGE and healthy controls from Vanderbilt University Medical Center between December 1, 2014, and November 30, 2015. The following 4 outcome groups were defined: overall AGE, norovirus-associated AGE, rotavirus-associated AGE, and nonnorovirus/nonrotavirus AGE. Multiple logistic regression was performed to evaluate the association between previous antibiotic use and the 4 AGE outcomes and with AGE severity. Results: Reported antibiotic use rates in the 3 months before illness onset were similar across the 4 AGE outcomes (overall AGE, 21%; norovirus-associated AGE, 23%; rotavirus-associated AGE, 28%; and nonnorovirus/nonrotavirus AGE, 22%) but were higher than that reported for healthy controls (9%). Compared with healthy controls, patients with AGE overall were 4.6 (95% confidence interval [CI], 1.8-11.4) times more likely to have reported antibiotic use in the 3 weeks before illness onset and 2.6 (95% CI, 1.7 4.1) times more likely to have reported antibiotic use within 3 months before illness onset. Similar results were found for the other specific AGE outcomes. For the overall AGE group, the odds of antibiotic use in the 3 months before illness onset was 3.5 (95% CI, 1.8-7.1) times higher for inpatients than for outpatients. Conclusions: Previous antibiotic use among children was associated with increased odds of AGE, irrespective of etiology, and this association was stronger with more recent antibiotic use. Previous antibiotic use was associated also with more severe AGE. PMID- 29788405 TI - Cohort Profile: The Swedish Longitudinal Occupational Survey of Health (SLOSH). PMID- 29788406 TI - An informed decision between cleavage-stage and blastocyst-stage transfer in IVF requires data on the transfers of frozen-thawed embryos. PMID- 29788408 TI - Effects of 4-Hydroxy-2,3,3',4',5-Pentachlorobiphenyl (4-OH-CB107) on Liver Transcriptome in Rats: Implication in the Disruption of Circadian Rhythm and Fatty Acid Metabolism. AB - Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1, aryl hydrocarbon receptor nuclear translocator-like protein 1, cryptochrome circadian clock 1, and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase, in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase, indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor related fatty acid metabolism. PMID- 29788409 TI - Wider implications of the differential diagnosis of sarcoid-related pulmonary cavitation. PMID- 29788407 TI - Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells. AB - Background: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage. Methods: Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis. Results: SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells. Conclusions: These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes. PMID- 29788410 TI - Differentiation Between Pediatric Irritable Bowel Syndrome and Inflammatory Bowel Disease Based on Fecal Scent: Proof of Principle Study. AB - Background: The diagnostic work-up of pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) commonly includes invasive tests for discrimination from inflammatory bowel disease (IBD). As this carries a high burden on patients, an ongoing need exists for development of noninvasive diagnostic biomarkers for IBS and FAP-NOS. Several studies have shown microbiota alterations in IBS/FAP, which are considered to be reflected by fecal volatile organic compounds (VOCs). The object of the study was to evaluate whether pediatric IBS/FAP-NOS could be discriminated from IBD and healthy controls by fecal VOC analysis. Methods: IBS/FAP-NOS was diagnosed according to the ROME IV criteria, and de novo IBD patients and healthy controls (HCs) aged 4 to 17 years were matched on age and sex. Fecal VOCs were analyzed by means of field asymmetric ion mobility spectrometry. Results: Fecal VOCs of 15 IBS/FAP NOS, 30 IBD (15 ulcerative colitis, 15 Crohn's disease) patients and 30 HCs were analyzed and compared. Differentiation between IBS/FAP-NOS and IBD was feasible with high accuracy (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.88-1; P < 0.00001). IBS/FAP-NOS profiles could not be differentiated from HCs (AUC, 0.59; 95% CI, 0.41-0.77; P = 0.167), whereas IBD profiles could with high accuracy (AUC, 0.96; 95% CI, 0.93-1; P < 0.00001). Conclusion: Pediatric IBS/FAP-NOS could be differentiated from IBD by fecal VOC analysis with high accuracy, but not from healthy controls. The latter finding limits the potential of fecal VOCs to serve as a diagnostic biomarker for IBS/FAP-NOS. However, VOC could possibly serve as additional noninvasive biomarker to differentiate IBS/FAP NOS from IBD. 10.1093/ibd/izy151_video1izy151.video15786446046001. PMID- 29788411 TI - Pathogenesis of duck circovirus genotype 1 in experimentally infected Pekin ducks. AB - Ducks infected with duck circovirus (DuCV) exhibit feathering disorder, growth retardation, and low body weight. The virus can induce immunosuppression and increase rates of infection caused by other pathogens. The purpose of the present study was to investigate the pathogenesis of DuCV in experimentally infected Pekin ducks. At postmortem examination, gross lesions were observed in the immune organs including bursa of Fabricius (BF), thymus, and spleen. Hemorrhage, lymphocytic depletion, necrosis, and degeneration were observed in the bursal tissues by histological examination. The TUNEL assay was performed with bursal tissue. There was a significant difference of the apoptosis rate between the negative and DuCV-infected ducks. The earliest time point for detection of DuCV DNA in sera, cloacal swabs, and organs was 1 wk post-infection (WPI). Viral shedding was persistent and detectable at the end of the experiment (10 WPI). The findings provide evidence that horizontal transmission and persistent infection are the characteristics of DuCV. The organ with the highest mean viral load was the spleen, followed by BF, cecal tonsil, lung, thymus, liver, and kidney. We successfully established an experimental DuCV genotype 1 (DuCV-1) infection in Pekin ducks and demonstrated the pathogenicity and persistence of DuCV-1. In conclusion, DuCV-1 caused extensive damage to the immune organs that may have resulted in immunosuppression. Pathobiological characteristics of DuCV-1 include systemic infection, persistent infection, and horizontal transmission. These features allow DuCV-1 to circulate more easily in farms and increase the susceptibility of ducks to other diseases. PMID- 29788412 TI - Treatment of Mal de Debarquement Syndrome in a Deployed Environment. AB - We report the case of a 26-year-old Caucasian female with persistent sensations of forward and reverse movement with spontaneous onset. This worsened over 4 wk. The patient reported an episode of these symptoms 5 mo prior, which lasted for 3 mo before improving. Our case details the treatment of Mal de Debarquement syndrome, or Disembarkment Syndrome, in a deployed military environment. Mal de Debarquement was a term originally coined to describe the persistent sensation of rocking back and forth after disembarking a boat and returning to land. This is normal, and usually only lasts for minutes to hours. When it persists, it is called Mal de Debarquement Syndrome. The onset frequently coincides with travel and most commonly by boat, however it can also occur spontaneously as in this case. Currently, there are three different treatment options. The first involves medications that are often sedating. The second uses magnetic resonance imaging at high frequency to stimulate the areas of the brain thought to be involved. The third option is a form of physical therapy termed re-adaptation of the vestibular ocular reflex. As we were in a deployed military environment the first two options were unsafe and unavailable respectively. We employed an improvised version of re-adaptation of the vestibular ocular reflex. The patient demonstrated a 50% reduction in symptoms following 1 wk of treatment and as a result was safely able to complete her deployment. PMID- 29788413 TI - ezTag: tagging biomedical concepts via interactive learning. AB - Recently, advanced text-mining techniques have been shown to speed up manual data curation by providing human annotators with automated pre-annotations generated by rules or machine learning models. Due to the limited training data available, however, current annotation systems primarily focus only on common concept types such as genes or diseases. To support annotating a wide variety of biological concepts with or without pre-existing training data, we developed ezTag, a web based annotation tool that allows curators to perform annotation and provide training data with humans in the loop. ezTag supports both abstracts in PubMed and full-text articles in PubMed Central. It also provides lexicon-based concept tagging as well as the state-of-the-art pre-trained taggers such as TaggerOne, GNormPlus and tmVar. ezTag is freely available at http://eztag.bioqrator.org. PMID- 29788414 TI - The Contribution of Genetic Variation of Streptococcus Pneumoniae to the Clinical Manifestation of Invasive Pneumococcal Disease. AB - Background: Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype. Methods: The index cohort consisted of 349 patients admitted to two Dutch hospitals between 2000-2011 with pneumococcal bacteraemia. We performed genome wide association studies to identify pneumococcal lineages, genes and allelic variants associated with 23 clinical IPD phenotypes. The identified associations were validated in a nationwide (n=482) and a post-pneumococcal vaccination cohort (n=121). The contribution of confirmed pneumococcal genotypes to the clinical IPD phenotype, relative to known clinical predictors, was tested by regression analysis. Results: Among IPD patients, the presence of pneumococcal gene slaA was a nationwide confirmed independent predictor of meningitis (OR=10.5, p=0.001, 5% presence), as was sequence cluster 9 (predominant serotype 7F, OR=3.68, p=0.057, 11% presence). A set of 4 pneumococcal genes co-located on a prophage was a confirmed independent predictor of 30-day mortality (OR=3.4, p=0.003, 48% presence). We could detect the pneumococcal variants of concern in these patients' blood samples. Conclusions: In this study, knowledge of pneumococcal genotypic variants improved the clinical risk assessment for detrimental manifestations of IPD. This provides us with novel opportunities to target, anticipate or avert the pathogenic effects related to particular pneumococcal variants, and indicates that information on pneumococcal genotype is important for the diagnostic and treatment strategy in IPD. Ongoing surveillance is warranted to monitor the clinical value of information on pneumococcal variants in dynamic microbial and susceptible host populations. PMID- 29788415 TI - Association of e-cigarette use with oral health: a population-based cross sectional questionnaire study. AB - Background: The impact of daily or intermittent electronic cigarette (e cigarette) use on oral health is unknown. Methods: We performed a cross-sectional analysis using the 2016 Behavioral Risk Factor Surveillance System data. Poor oral health was determined by the number of permanent teeth removed due to non traumatic causes, and e-cigarette use determined by daily or intermittent use within 30 days prior to survey administration. We performed logistic regression analysis to test associations between e-cigarette use and oral health with adjustment for factors associated with poor oral health, survey clustering, strata and weight. Results: We included survey responses from 456 343 adults. Over half of respondents (51.5%) reported having at least one permanent tooth removed because of tooth decay or gum disease in their lifetime. Daily e cigarette use was reported by 4957 (1.1%) of respondents. In multivariable analysis, daily e-cigarette use, was independently associated with a 78% higher odds of poor oral health (adjusted OR = 1.78, 95% CI: 1.39-2.30; P < 0.001). Conclusions: In a population-based health survey of US adults, self-reported health behavior and outcomes, daily use, but not intermittent use of e-cigarettes was independently associated with poor oral health. Care must be exercised in seeking 'healthier' cigarette alternatives. PMID- 29788416 TI - Evaluation of Rapid vs Standard Infliximab Infusions in the Pediatric Population. AB - Background: Rapid 1-hour infliximab infusions have been safely implemented in adults, but studies of these rapid infusions in pediatric patients are limited. This study's primary objective was to determine the safety of 1-hour infliximab infusions compared with standard 2- to 3-hour infusions in children with inflammatory bowel disease and other autoimmune disorders. Methods: We conducted an institutional review board-approved prospective study using an unmatched historical control group at a freestanding children's hospital comparing rapid vs standard infusion rates of infliximab and the use of premedications and immunomodulatory agents on the frequency of early and delayed infusion reactions. Results: There were 50 subjects with 540 total standard (2- to 3-hour) infusions in the retrospective group and 66 subjects with 545 total rapid (1-hour) infusions assessed in the prospective group. Although the prospective group received a significantly higher infliximab dose, was significantly less likely to receive premedication, and was significantly more likely to receive another immunomodulatory agent, only 2 instances of potential infusion reactions occurred in the 545 rapid infusions (0.36%; 95% confidence interval [CI], 0.22%-11.01%; 3% of patients) administered in the prospective group compared with 1 documented infusion reaction (0.19%; 95% CI, 0.0%-11.47%; 2% of patients) in the retrospective group (odds ratio, 0.65; 95% CI, 0.01-12.93; P = 0.99). Conclusions: This study suggests that rapid infusion of infliximab over 1 hour is not associated with an increased risk of infusion reactions when compared with standard 2- to 3-hour infusions and can be safely used in children with no previous reaction to standard infusions to treat inflammatory bowel disease and other autoimmune diseases. PMID- 29788418 TI - Efficacy of bezlotoxumab based on timing of administration relative to start of antibacterial therapy for Clostridium difficile infection. AB - Background: The fully human monoclonal antibody bezlotoxumab binds Clostridioides (Clostridium) difficile toxin B and reduces recurrence rates in patients with C. difficile infection (CDI) receiving antibacterial treatment for a primary or recurrent episode. Objectives: To investigate whether the timing of bezlotoxumab administration relative to the onset of antibacterial treatment affected clinical outcome in the Phase 3 trials MODIFY I (NCT01241552) and MODIFY II (NCT01513239). Methods: Initial clinical cure and CDI recurrence rates of participants who received bezlotoxumab or placebo were summarized by timing of infusion relative to the start of antibacterial drug treatment for CDI: 0-2, 3-4 and >=5 days after onset. Results: Of 1554 total participants, 649 (41.8%), 469 (30.1%) and 436 (28.1%) received an infusion 0-2, 3-4 and >=5 days after onset of antibacterial treatment for CDI, respectively. Regardless of timing of administration, there were no differences in initial clinical cure rates between participants receiving bezlotoxumab (range 77.8% to 81.4%) or placebo (77.8% to 81.7%). Bezlotoxumab efficacy was unaffected by timing of administration; rates of CDI recurrence were lower versus placebo in all subgroups (range 19.3% to 22.8% for bezlotoxumab and 31.7% to 35.8% for placebo). Timing of administration also had no effect on time to resolution of diarrhoea, which was achieved by the end of antibacterial treatment in ~95% of participants in both bezlotoxumab and placebo groups. Conclusions: Bezlotoxumab is effective in preventing CDI recurrence and can be administered at any time before ending antibacterial drug treatment. PMID- 29788419 TI - Using Vedolizumab to treat Severe Sweet's Syndrome in a Patient with Ulcerative Colitis. PMID- 29788417 TI - Poor feed efficiency in sheep is associated with several structural abnormalities in the community metabolic network of their ruminal microbes. AB - Ruminant animals have a symbiotic relationship with the microorganisms in their rumens. In this relationship, rumen microbes efficiently degrade complex plant derived compounds into smaller digestible compounds, a process that is very likely associated with host animal feed efficiency. The resulting simpler metabolites can then be absorbed by the host and converted into other compounds by host enzymes. We used a microbial community metabolic network inferred from shotgun metagenomics data to assess how this metabolic system differs between animals that are able to turn ingested feedstuffs into body mass with high efficiency and those that are not. We conducted shotgun sequencing of microbial DNA from the rumen contents of 16 sheep that differed in their residual feed intake (RFI), a measure of feed efficiency. Metagenomic reads from each sheep were mapped onto a database-derived microbial metabolic network, which was linked to the sheep metabolic network by interface metabolites (metabolites transferred from microbes to host). No single enzyme was identified as being significantly different in abundance between the low and high RFI animals (P > 0.05, Wilcoxon test). However, when we analyzed the metabolic network as a whole, we found several differences between efficient and inefficient animals. Microbes from low RFI (efficient) animals use a suite of enzymes closer in network space to the host's reactions than those of the high RFI (inefficient) animals. Similarly, low RFI animals have microbial metabolic networks that, on average, contain reactions using shorter carbon chains than do those of high RFI animals, potentially allowing the host animals to extract metabolites more efficiently. Finally, the efficient animals possess community networks with greater Shannon diversity among their enzymes than do inefficient ones. Thus, our system approach to the ruminal microbiome identified differences attributable to feed efficiency in the structure of the microbes' community metabolic network that were undetected at the level of individual microbial taxa or reactions. PMID- 29788420 TI - Effects of rearing systems on reproductive hormones secretion and their receptors gene expression in Xianju chickens under summer conditions. AB - Previous study in our lab showed that indigenous Xianju chickens from free-range system (FRS) under summer conditions had lower egg production than those from conventional cage rearing system (CRS). The objective of this study was to preliminarily determine the FRS-dependent mechanism of depressing laying performance according to determining the effect of rearing systems on reproductive hormones secretion and their receptors mRNA expression in Xianju chickens reared under summer conditions. A total of 360 indigenous Xianju chickens were randomly allocated to CRS and FRS groups, each of which included 5 replicates of 36 hens. The experiment lasted between 21 and 29 wk of age. We found that the ovarian weight, numbers of small yellow follicles, and large white follicles in the FRS group were lower than those in the CRS group (P < 0.05). Changing from CRS to FRS increased serum concentrations of prolactin and decreased serum-luteinizing hormone and progesterone levels (P < 0.05). Gene expressions in the preovulatory follicles from FRS hens were upregulated for prolactin receptor and downregulated for luteinizing hormone receptor and progesterone receptor, compared to those from CRS hens (P < 0.05). It can be concluded that changing from CRS to FRS in the current experimental conditions depressed egg production traits in Xianju chickens by inducing a synergistic activity of reproductive hormones and the gene expressions of their receptors. PMID- 29788421 TI - Predicting Viral Failure in Human Immunodeficiency Virus Perinatally Infected Youth With Persistent Low-Level Viremia on Highly Active Antiretroviral Therapy. AB - Background: Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20-75 copies/mL) and 1000 copies/mL. All patients were perinatally infected, under 22 years of age, observed for at least 24 months of consecutive follow-up between May 2008 and July 2014, and received their HIV care at the University of Miami Miller School of Medicine. Of the 349 subjects screened, 100 were eligible for analysis. Virological failure was defined as 3 or more consecutive VLs greater than 1000 copies/mL. Multiple logistic regression and receiver operator characteristic curves were used to identify patterns in VL that ultimately resulted in VF. Results: Fifteen of the 100 patients experienced VF. Higher log10 mean VL, positive slope of the VL (log10 copies/mL per day), and fewer clinic visits were associated with a higher probability of VF. Sensitivity and specificity were .87 and .95, respectively. Resistance was not found in 12 of 15 patients with VF. Conclusions: Patients with LLV that had fewer clinic visits and a trend toward increasing VLs had an increased risk of VF. Noncompliance seems to be a major component of VF. Physicians should emphasize the critical nature of medication adherence. PMID- 29788422 TI - N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users. AB - Background: Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods: Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results: In right inferior frontal cortex, N-acetyl-aspartate+N acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions: The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users. PMID- 29788423 TI - Variability in adolescent portal privacy features: how the unique privacy needs of the adolescent patient create a complex decision-making process. AB - Objective: Medical privacy policies, which are clear-cut for adults and young children, become ambiguous during adolescence. Yet medical organizations must establish unambiguous rules about patient and parental access to electronic patient portals. We conducted a national interview study to characterize the diversity in adolescent portal policies across a range of institutions and determine the factors influencing decisions about these policies. Methods: Within a sampling framework that ensured diversity of geography and medical organization type, we used purposive and snowball sampling to identify key informants. Semi structured interviews were conducted and analyzed with inductive thematic analysis, followed by a member check. Results: We interviewed informants from 25 medical organizations. Policies established different degrees of adolescent access (from none to partial to complete), access ages (from 10 to 18 years), degrees of parental access, and types of information considered sensitive. Federal and state law did not dominate policy decisions. Other factors in the decision process were: technology capabilities; differing patient population needs; resources; community expectations; balance between information access and privacy; balance between promoting autonomy and promoting family shared decision making; and tension between teen privacy and parental preferences. Some informants believed that clearer standards would simplify policy-making; others worried that standards could restrict high-quality polices. Conclusions: In the absence of universally accepted standards, medical organizations typically undergo an arduous decision-making process to develop teen portal policies, weighing legal, economic, social, clinical, and technological factors. As a result, portal access policies are highly inconsistent across the United States and within individual states. PMID- 29788424 TI - EXPERIMENTAL AND COMPUTATIONAL EVALUATION OF EFFECTIVE CENTRE FROM A LONG COUNTER AT NEUTRON METROLOGY LABORATORY IN BRAZIL. AB - A long counter detector was manufactured by the Institute of Advanced Studies (IEAV) and was characterised in the neutron low scattering room at Brazilian National Ionising Radiation Metrology Laboratory (LNMRI/IRD) to deploy a secondary Standard for neutron fluence. The effective centre was measured experimentally with 252Cf+D2O, 252Cf, 241AmBe and 238PuBe neutron sources, having average energies from 0.55 to 4.16 MeV. The experimental arrangement and detector construction were carefully reproduced in Monte Carlo simulations, and the computational results were found to be in good agreement with those from experiment. PMID- 29788426 TI - Progression of Low-Grade Glioma During Pregnancy With Subsequent Regression Postpartum Without Treatment-A Case Report. AB - BACKGROUND AND IMPORTANCE: This report illustrates a case of a low-grade glioma that showed significant disease progression during pregnancy, and then subsequent regression spontaneously in the postpartum period without treatment. This is a rare case of spontaneous glioma regression in the postpartum period, and may suggest underlying mechanisms of hormonal influences upon glioma progression. CLINICAL PRESENTATION: The patient is a 27-yr-old female who underwent placement of a right-sided ventriculoperitoneal shunt for aqueductal stenosis at 8 wk of age. At the age of 24 yr, she was evaluated for chronic headaches and was found on magnetic resonance imaging (MRI) for the first time to have a small nonenhancing tectal glioma that remained stable on follow-up MRI. At the age of 25 yr, she returned for annual follow-up after giving birth and reported a significant increase in headache frequency and severity during the pregnancy. Repeat imaging now showed a larger, contrast-enhancing lesion. A decision was made to pursue radiosurgery, but during the pretreatment planning phase, the lesion and symptoms regressed spontaneously, and the lesion has remained stable on repeat MRI studies over a 30-mo period since delivery of her child. CONCLUSION: A young woman with a tectal glioma developed symptomatic disease progression during pregnancy, and subsequently had regression of the lesion and symptoms in the postpartum period without treatment. This case supports watchful waiting in select cases and suggests a potential role of hormones in glioma progression. PMID- 29788425 TI - Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles. AB - Background: The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). Methods: We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score >6 or an Adragao score >=3. Results: CKD participants with VC had larger cumulants Rh of CPP2 {370 nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212 nm (IQR 169-315)] and compared with HV [168 nm (IQR 145-352), P < 0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10 nm increase in the Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P = 0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. Conclusions: Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5. PMID- 29788427 TI - Changes in Corticotrope Gene Expression Upon Increased Expression of Peptidylglycine alpha-Amidating Monooxygenase. AB - Throughout evolution, secretion has played an essential role in the ability of organisms and single cells to survive in the face of a changing environment. Peptidylglycine alpha-amidating monooxygenase (PAM) is an integral membrane monooxygenase, first identified for its role in the biosynthesis of neuroendocrine peptides released by the regulated secretory pathway. PAM was subsequently identified in Chlamydomonas reinhardtii, a unicellular green alga, where it plays an essential role in constitutive secretion and in ciliogenesis. Reduced expression of C. reinhardtii PAM resulted in significant changes in secretion and ciliogenesis. Hence, a screen was performed for transcripts and proteins whose expression responded to changes in PAM levels in a mammalian corticotrope tumor cell line. The goal was to identify genes not previously known to play a role in secretion. The screen identified transcription factors, peptidyl prolyl isomerases, endosomal/lysosomal proteins, and proteins involved in tissue-specific responses to glucose and amino acid availability that had not previously been recognized as relevant to the secretory pathway. Perhaps reflecting the dependence of PAM on molecular oxygen, many PAM-responsive genes are known to be hypoxia responsive. The data highlight the extent to which the performance of the secretory pathway may be integrated into a wide diversity of signaling pathways. PMID- 29788428 TI - PUF60-activated exons uncover altered 3' splice-site selection by germline missense mutations in a single RRM. AB - PUF60 is a splicing factor that binds uridine (U)-rich tracts and facilitates association of the U2 small nuclear ribonucleoprotein with primary transcripts. PUF60 deficiency (PD) causes a developmental delay coupled with intellectual disability and spinal, cardiac, ocular and renal defects, but PD pathogenesis is not understood. Using RNA-Seq, we identify human PUF60-regulated exons and show that PUF60 preferentially acts as their activator. PUF60-activated internal exons are enriched for Us upstream of their 3' splice sites (3'ss), are preceded by longer AG dinucleotide exclusion zones and more distant branch sites, with a higher probability of unpaired interactions across a typical branch site location as compared to control exons. In contrast, PUF60-repressed exons show U-depletion with lower estimates of RNA single-strandedness. We also describe PUF60 regulated, alternatively spliced isoforms encoding other U-bound splicing factors, including PUF60 partners, suggesting that they are co-regulated in the cell, and identify PUF60-regulated exons derived from transposed elements. PD associated amino-acid substitutions, even within a single RNA recognition motif (RRM), altered selection of competing 3'ss and branch points of a PUF60-dependent exon and the 3'ss choice was also influenced by alternative splicing of PUF60. Finally, we propose that differential distribution of RNA processing steps detected in cells lacking PUF60 and the PUF60-paralog RBM39 is due to the RBM39 RS domain interactions. Together, these results provide new insights into regulation of exon usage by the 3'ss organization and reveal that germline mutation heterogeneity in RRMs can enhance phenotypic variability at the level of splice-site and branch-site selection. PMID- 29788430 TI - Indicators to assess the functionality of clubfoot clinics in low-resource settings: a Delphi consensus approach and pilot study. AB - Background: This study aims to determine the indicators for assessing the functionality of clubfoot clinics in a low-resource setting. Methods: The Delphi method was employed with experienced clubfoot practitioners in Africa to rate the importance of indicators of a good clubfoot clinic. The consistency among the participants was determined with the intraclass correlation coefficient. Indicators that achieved strong agreement (mean>=9 [SD <1.5]) were included in the final consensus definition. Based on the final consensus definition, a set of questions was developed to form the Functionality Assessment Clubfoot Clinic Tool (FACT). The FACT was used between February and July 2017 to assess the functionality of clinics in the Zimbabwe clubfoot programme. Results: A set of 10 indicators that includes components of five of the six building blocks of a health system-leadership, human resources, essential medical equipment, health information systems and service delivery-was produced. The most common needs identified in Zimbabwe clubfoot clinics were a standard treatment protocol, a process for surgical referrals and a process to monitor dropout of patients. Conclusions: Practitioners had good consistency in rating indicators. The consensus definition includes components of the World Health Organization building blocks of health systems. Useful information was obtained on how to improve the services in the Zimbabwe clubfoot programme. PMID- 29788432 TI - Sucrose challenges to Streptococcus mutans biofilms and the curve fitting for the biofilm changes. AB - The relationship between sugar level and development of dental caries has long been a main topic in dentistry. However, as a ubiquitous component of the modern diet, sucrose is mainly derived from three meals a day, rather than a long time exposure. In this study, various concentrations of sucrose were provided to Streptococcus mutans biofilms for 1 h per exposure (three times per day) to imitate a human meal pattern. And then the relationship between sucrose concentration and changes in the treated biofilms was determined. The results indicated that the components and acid production of the treated biofilms changed in a second-order polynomial curve pattern with sucrose concentration increase, which were confirmed by CLSM and SEM analyses. However, gene expression related to extracellular polysaccharides (EPS) formation, acid production and tolerance was up-regulated with sucrose concentration increase, which might have been due to compensation for the decrease in EPS formation and acid production by the biofilms at higher concentrations of sucrose. These findings suggest that sucrose in the range of 1%-5% can support the highest acid production and accumulation of S. mutans biofilms, which may further increase its cariogenic potential. However, additional studies are required to confirm the relationships in human cariogenic biofilms. PMID- 29788431 TI - Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy. AB - Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM. PMID- 29788429 TI - Corticosteroid use endpoints in neuro-oncology: Response Assessment in Neuro Oncology Working Group. AB - Background: Corticosteroids are the mainstay of treatment for peritumor edema but are often associated with significant side effects. Therapies that can reduce corticosteroid use would potentially be of significant benefit to patients. However, currently there are no standardized endpoints evaluating corticosteroid use in neuro-oncology clinical trials. Methods: The Response Assessment in Neuro Oncology (RANO) Working Group has developed consensus recommendations for endpoints evaluating corticosteroid use in clinical trials in both adults and children with brain tumors. Results: Responders are defined as patients with a 50% reduction in total daily corticosteroid dose compared with baseline or reduction of the total daily dose to <=2 mg of dexamethasone (or equivalent dose of other corticosteroid); baseline dose must be at least 4 mg of dexamethasone daily (or equivalent dose of other corticosteroids) for at least one week. Patients must have stable or improved Neurologic Assessment in Neuro-Oncology (NANO) score or Karnofsky performance status score or Eastern Cooperative Oncology Group (ECOG) (Lansky score for children age <16 y), and an improved score on a relevant clinical outcome assessment tool. These criteria must be sustained for at least 4 weeks after baseline assessment to be considered a response, and are confirmed 4 weeks after that (ie, 8 wk after baseline assessment) to be considered a sustained response. Conclusions: This RANO proposal for corticosteroid use endpoints in neuro-oncology clinical trials may need to be refined and will require prospective validation in clinical studies. PMID- 29788433 TI - Metabolic Footprinting of Fermented Milk Consumption in Serum of Healthy Men. AB - Background: Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. Objective: To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion. Methods: A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2 wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS-based untargeted metabolomics. Results: Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results. Conclusion: Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel health effects of fermented dairy products is warranted.This trial was registered at clinicaltrials.gov as NCT02230345. PMID- 29788435 TI - Air embolism after CT-guided percutaneous lung biopsy. PMID- 29788436 TI - S-25OHD Is Associated With Hand Grip Strength and Myopathy at 5 Years in Girls: An Odense Child Cohort Study. AB - Context: Severe vitamin D deficiency may lead to myopathy in adults. Little is known about vitamin D and muscle strength in children. Objective: To test whether hand grip strength (HGS) in 5-year-old children is associated with serum 25 hydroxyvitamin D (S-25OHD). Design: Observational study in the population-based Odense Child Cohort, Denmark. At 5 years, anthropometrics, body fat percentage by skinfold measurements, HGS (n = 881), and S-25OHD2+3 (n = 499) were obtained. Results: Mean (SD) HGS was higher for boys compared with girls [8.76 (1.76) vs 8.1 (1.64) kg, P < 0.001]. Mean (SD) 5-year S-25OHD was 70.7 (24.5) nmol/L. HGS was directly associated with height in girls and with weight (directly) and body fat percentage (inversely) in both sexes (P < 0.01 for all). In girls, 5-year S 25OHD was associated with HGS, adjusting for height, weight, and body fat percentage [beta = 0.011 (95% CI: 0.004; 0.019), P = 0.003]. S-25OHD >=75 nmol/L was associated with higher HGS compared with values <50 nmol/L [adjusted beta = 0.783 (95% CI: 0.325; 1.241), P = 0.001]. The odds of having myopathy (HGS <10th percentile) were reduced by approximately 70% for S-25OHD >=50 vs <50 nmol/L [adjusted OR: 0.310 (95% CI: 0.126; 0.762), P = 0.011]. No associations were seen for boys. Pregnancy or umbilical cord S-25OHD did not associate with 5-year HGS. Conclusions: Five-year S-25OHD was independently associated with HGS and myopathy in girls but not in boys. Muscle strength may be dependent on vitamin D status even in the higher range in preschool girls. The sex difference remains unexplained. PMID- 29788434 TI - A novel mouse model of testicular granulosa cell tumors. AB - STUDY QUESTION: What is the role of dysregulated transforming growth factor beta (TGFB) signaling in the development of sex cord-stromal tumors in the testis? SUMMARY ANSWER: Overactivation of TGFB signaling results in the development of testicular tumors resembling granulosa cell tumors (GrCTs). WHAT IS KNOWN ALREADY: In an earlier study, we demonstrated that constitutively active TGFB receptor 1 (TGFBR1) in ovarian somatic cells promotes the development of ovarian GrCTs. However, the consequence of dysregulation of TGFB signaling in the pathobiology of the testis, remains poorly defined. STUDY DESIGN, SIZE, DURATION: To identify the impact of dysregulation of TGFB signaling on the testis, we generated mice with constitutive activation of TGFBR1 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase. The effect of constitutively active TGFBR1 on testis development and the timeline of testicular tumor formation were examined. We further investigated the molecular features of testicular tumors and determined the expression of beta-catenin (CTNNB1) known to be involved in testicular GrCT development. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male mice with constitutive activation of TGFBR1 were examined at various developmental stages (i.e. from 1 week up to 6 months) along with controls. Testis samples were collected and processed for histological and molecular analyses, including haematoxylin and eosin (H and E) staining, real time PCR, immunohistochemistry, immunofluorescence and western blotting. Immunostaining/immunoblotting and real-time PCR experiments were performed using at least three animals per genotype. Data are presented as mean +/- SEM. Statistical significance was determined using unpaired two-tail t-test and reported when P value is <0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Mice harboring constitutively active TGFBR1 in the testes developed tumors resembling testicular GrCTs, a rare type of tumors in the testis. The formation of testicular tumors led to altered cell proliferation, loss of germ cells and defective spermatogenesis. Immunohistochemically, these tumors were positive for inhibin alpha (INHA), forkhead box O1 (FOXO1), and more importantly, forkhead box L2 (FOXL2), a protein specifically expressed in the ovary and required for normal granulosa cell differentiation and function. Consistent with the immunohistochemical findings, FOXL2 proteins were only detectable in testes of TGFBR1-CAAcre mice but not those of controls by western blotting, suggesting potential alteration of Sertoli cell fate. To explore mechanisms underlying the tumor-promoting effect of TGFBR1 overactivation, we examined the expression of CTNNB1. The results revealed increased expression of CTNNB1 in testicular tumors in TGFBR1-CAAcre mice. Collectively, this study uncovered tumorigenic function of enhanced TGFB signaling in the testis. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed using mice, and the direct relevance of the experimental paradigm and findings to human testicular GrCTs awaits further investigation. Of note, constitutive activation of TGFBR1 was employed to enhance TGFB/SMAD signaling activity and may not be interpreted as the genetic cause of the disease. WIDER IMPLICATIONS OF THE FINDINGS: This mouse model may prove to be a useful addition to the mouse genetics toolkit for GrCT research. Our finding that dysregulation of TGFB signaling results in the development of testicular GrCTs supports a common origin between Sertoli cells and granulosa cells, and highlights the paramount importance of balanced TGFB signaling in reproduction and development. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Institutes of Health grant R03HD082416 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the New Faculty Start-up Funds from Texas A&M University awarded to Q.L. The authors declare no competing interest. PMID- 29788437 TI - Retromastoid Approach for Posterior Fossa Skull Base Rosai-Dorfman Disease-A Rare Pathology: 3-Dimensional Operative Video. AB - Rosai-Dorfman disease, originally described by Juan Rosai and Ronald F. Dorfman, is a rare benign histiocytic proliferative disorder, classically presenting with massive lymphadenopathy and a self-limiting clinical course.1 Isolated intracranial skull base involvement is extremely rare and often resembles meningiomas, schwannomas, or other benign skull base lesions.2 The disease is difficult to diagnose radiographically, and tissue diagnosis with open skull base approaches has significant perioperative risks.2,3 We present the case of a 48-yr old Caucasian male presenting with progressively worsening headaches, giddiness, hearing difficulty, and diplopia. Magnetic resonance imaging of the brain revealed T1-weighted isointense, T2-weighted hypointense, and contrast-enhancing dural-based lesion in the left cerebellopontine angle. The patient underwent maximally safe resection of the lesion through the retromastoid approach with careful preservation of the lower cranial nerve complex. The intraoperative findings of a variegated and lobulated mass adherent to the skull base, the surgical strategy of safe resection, and eventual good outcome in this patient are depicted in this 3-dimensional video presentation. The majority of patients with skull base Rosai-Dorfman disease reported in literature have had stable or regression of disease (78%) after initial conservative surgical treatment and hence aggressive surgical resection is of unproven efficacy.3 The patient has consented to depiction of his surgical video and intraoperative images in this video manuscript. PMID- 29788438 TI - Efficacy of polymers from spontaneous carotenoid oxidation in reducing necrotic enteritis in broilers. AB - This study evaluated the preventive effect of the spontaneous oxidation of beta carotene (OxC-beta) in broiler chickens with necrotic enteritis by Clostridium perfringens taking into consideration various parameters including clinical signs, body weight, intestinal lesion severity, and bacterial enumeration. The mean body weight of the OxC-beta treatment groups increased significantly (P < 0.05) compared to that of the C. perfringens challenge group. Intestinal lesion scores due to C. perfringens infection were significantly alleviated by OxC-beta treatment (P < 0.05), and the number of clostridial bacteria in intestine was reduced by OxC-beta in a dose-dependent manner. OxC-beta in feed contributes to the prevention of necrotic enteritis in commercial broiler chicken, and has a positive effect in improving productivity. PMID- 29788439 TI - Repair of Temporal Bone Defects via the Middle Cranial Fossa Approach: Treatment of 2 Pathologies With 1 Operation. AB - BACKGROUND: Temporal bone dehiscence (TBD) often results in leakage of cerebrospinal fluid (CSF) and/or encephalocele. TBD can also occur over the superior semicircular canal, causing debilitating vertigo. Both can be repaired surgically, but traditional treatment is focused only on one pathology, not both. OBJECTIVE: To report our experience in the treatment of TBD via the middle cranial fossa (MCF) approach. METHODS: A retrospective review was conducted for all patients who underwent MCF approach for surgical repair of any temporal fossa dehiscence. RESULTS: A total of 34 patients underwent a total of 37 surgeries. Obesity was prevalent; 21 patients (61.8%) were obese (BMI [body mass index] > 30 kg/m2), and 7 (20.6%) were overweight (BMI 25-30 kg/m2). The most common presenting symptom was hearing disturbance (70.3%), followed by otorrhea (51.4%). Empty sella was noted on computed tomography or magnetic resonance imaging in 15 patients (45.5%). Eight of the 34 patients (23.5%) were found to have superior semicircular canal dehiscence (SCD). Hearing improved with surgical intervention in 25 of 26 patients with hearing loss as a presenting symptom (96%). CSF resolved in 18 of 19 cases (95%). Seventy-three percent of patients reported at least minimal improvement in vertigo. CONCLUSION: TBD may present with symptoms of CSF leak/encephalocele, but may also present with superior SCD. We recommend consistent review of the temporal bone imaging to check for superior SCD, and repair of the SCD first to prevent complications involving the labyrinth and cochlea. MCF approach using a multilayer repair without a lumbar drain is highly effective with minimal risk of complications. PMID- 29788440 TI - Exercise-Induced Hypoalgesia After Isometric Wall Squat Exercise: A Test-Retest Reliabilty Study. AB - Background: Isometric exercises decrease pressure pain sensitivity in exercising and nonexercising muscles known as exercise-induced hypoalgesia (EIH). No studies have assessed the test-retest reliability of EIH after isometric exercise. This study investigated the EIH on pressure pain thresholds (PPTs) after an isometric wall squat exercise. The relative and absolute test-retest reliability of the PPT as a test stimulus and the EIH response in exercising and nonexercising muscles were calculated. Methods: In two identical sessions, PPTs of the thigh and shoulder were assessed before and after three minutes of quiet rest and three minutes of wall squat exercise, respectively, in 35 healthy subjects. The relative test-retest reliability of PPT and EIH was determined using analysis of variance models, Person's r, and intraclass correlations (ICCs). The absolute test-retest reliability of EIH was determined based on PPT standard error of measurements and Cohen's kappa for agreement between sessions. Results: Squat increased PPTs of exercising and nonexercising muscles by 16.8% +/- 16.9% and 6.7% +/- 12.9%, respectively (P < 0.001), with no significant differences between sessions. PPTs within and between sessions showed moderately strong correlations (r >= 0.74) and excellent (ICC >= 0.84) within-session (rest) and between-session test-retest reliability. EIH responses of exercising and nonexercising muscles showed no systematic errors between sessions; however, the relative test-retest reliability was low (ICCs = 0.03-0.43), and agreement in EIH responders and nonresponders between sessions was not significant (kappa < 0.13, P > 0.43). Conclusions: A wall squat exercise increased PPTs compared with quiet rest; however, the relative and absolute reliability of the EIH response was poor. Future research is warranted to investigate the reliability of EIH in clinical pain populations. PMID- 29788441 TI - Decision-Making Involvement and Prediction of Adherence in Youth With Type 1 Diabetes: A Cohort Sequential Study. AB - Objective: To assess developmental trajectories of decision-making involvement (DMI), defined as the ways in which parents and children engage each other in decision-making about illness management, in youth with type 1 diabetes (T1D) and examine the effects of DMI on levels of and changes in adherence with age. Methods: Participants included 117 youth with T1D, enrolled at ages 8-16 years and assessed five times over 2 years. The cohort sequential design allowed for the approximation of the longitudinal curve from age 8 to 19 from overlapping cohort segments. Children and parents completed the Decision-Making Involvement Scale, which yields subscales for different aspects of DMI, and a self-report adherence questionnaire. Mixed-effects growth curve modeling was used for analysis, with longitudinal measures nested within participant and participants nested within cohort. Results: Most aspects of DMI (Parent Express, Parent Seek, Child Express, and Joint) increased with child age; scores on some child report subscales (Parent Express, Child Seek, and Joint) decreased after age 12-14 years. After accounting for age, Child Seek, Child Express, and Joint were associated with overall higher levels of adherence in both child (estimates = 0.08-0.13, p < .001) and parent (estimates = 0.07- 0.13, p < .01) report models, but they did not predict changes in adherence with age. Conclusion: These data suggest that helping children to be more proactive in T1D discussions, by encouraging them to express their opinions, share information, and solicit guidance from parents, is a potential target for interventions to enhance effective self-management. PMID- 29788442 TI - Response to the comment on "Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma" by Bielamowicz et al. PMID- 29788443 TI - Pediatric Infectious Diseases Meets the Future. AB - Pediatric infectious diseases physicians are dedicated to the diagnosis, prevention, and management of infections in children. As such, we play large, and important, roles in the clinical care of children from birth to late adolescence and in infection prevention, antimicrobial stewardship, research pertaining to infections, public health, international and global health, and advocacy for children's health. Furthermore, we are critical to the education of future physicians (in general), pediatricians, and infectious diseases doctors. In addition to diagnosing and treating bacterial, fungal, viral, and parasitic infections known through the ages, we have been at the forefront of meeting today's new infectious threats to children's health, which include the following: antibiotic-resistant organisms; hospital-acquired infections; global outbreaks such as Ebola, Zika, human immunodeficiency virus-acquired immune deficiency syndrome, and new strains of influenza; infections in immunocompromised children; vaccine-preventable infections; the inefficient use of medical resources; and the high cost of medical care. PMID- 29788445 TI - Lung Cancer Screening and Smoking Cessation: Never Too Early or Too Late. PMID- 29788444 TI - Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation. AB - Context: In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. Objective: To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Design, Setting, Participants, and Interventions: Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16 degrees C for 2 hours to quantify CIBA. Main Outcome Measures: CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry. Results: Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (beta = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (beta = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and beta = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively). Conclusion: Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain. PMID- 29788446 TI - Differential response to heat stress in outer and inner onion bulb scales. AB - The formation of brown protective skin in onion bulbs can be induced by rapid post-harvest heat treatment. Onions that are peeled to different depths and are exposed to heat stress show that only the outer scales form the dry brown skin, whereas the inner scales maintain high water content and do not change color. Our study demonstrates that browning of the outer scale during heat treatment is due to an enzymatic process that is associated with high levels of oxidation components, such as peroxidase and quercetin glucoside. De novo transcriptome analysis revealed differential molecular responses of the outer and inner scales to heat stress. Genes involved in lipid metabolism, oxidation pathways, and cell wall modification were highly expressed in the outer scale during heating. Defense response-related genes such as those encoding heat-shock proteins, antioxidative stress defense, or production of osmoprotectant metabolites were mostly induced in the inner scale in response to heat exposure. These transcriptomic data led to a conceptual model that suggests sequential processes for the development of browning and desiccation of the outer scale versus processes associated with defense response and heat tolerance in the inner scales. PMID- 29788448 TI - Inhibition of Endothelial Progenitor Cells May Explain the High Cardiovascular Event Rate in Patients with Rheumatoid Arthritis. AB - Background: Rheumatoid arthritis (RA) patients may suffer cardiovascular (CV) events much more than the general population, and CV disease is the leading cause of death in patients with RA. Our hypothesis was that impaired function of endothelial progenitor cells may contribute to endothelial dysfunction and the clinical CV events of patients with RA. Methods: 27 RA patients (9 males and 18 females) with an active disease and 13 healthy subjects who served as the control group (9 males and 4 females) were enrolled to this prospective study. The ability to grow in culture colony-forming units of endothelial progenitor cells (CFU-EPCs) was measured, as well as their endothelial function using high resolution ultrasonography of the brachial artery, and levels of C reactive protein (CRP) in the serum. For statistical analysis we used the students T-test test. Results: As a group, patients with RA were older (p < 0.0001), had severe endothelial dysfunction (<0.0001), with impaired ability to grow CFU-EPCs (<0.0001), and a higher inflammatory state (p = 0001). No difference was observed in BMI. All RA patients had an active disease (DAS28 3.9+/-0.9) for 9.2+/-6.5 years. The same differences were observed in both genders. Conclusions: Patients with RA had an impaired ability to grow endothelial progenitor cells and severe endothelial dysfunction. Inability to grow colonies of endothelial progenitor cells reflects the impaired regenerative capacity of patients with RA, and may explain the endothelial dysfunction and the high CV event rate among patients with RA. PMID- 29788447 TI - Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes. AB - Background: Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy. Methods: Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes, and viral spread in the presence or absence of the NK-1R antagonists aprepitant and rolapitant. Results: VZV infection of HA-sps induced nuclear localization of full-length and truncated NK-1R in the absence of the endogenous ligand, subP, and was associated with extensive lamellipodia formation and viral spread that was inhibited by NK 1R antagonists. Conclusions: We have identified a novel, subP-independent, proviral function of nuclear NK-1R associated with lamellipodia formation and viral spread that is distinct from subP-induced NK-1R cell membrane/cytoplasmic localization without lamellipodia formation. These results suggest that binding of a putative viral ligand to NK-1R produces a dramatically different NK-1R downstream effect than binding of subP. Finally, the NK-1R antagonists aprepitant and rolapitant provide promising alternatives to nucleoside analogs in treating VZV infections, including myelopathy. PMID- 29788450 TI - Callus initiation from root explants employs different strategies in rice and Arabidopsis. AB - Callus formation in tissue culture follows the rooting pathway and newly formed callus seems to be a group of root primordium-like cells. However, it is not clear whether there are multiple mechanisms of callus initiation in different species and in different organs. Here we show that the OsIAA11-mediated pathway is specifically and strictly required for callus initiation in the lateral root (LR) formation region of the primary root (PR) but not for callus initiation at the root tip or the stem base in rice. OsIAA11 and its Arabidopsis homologue AtIAA14 are key players in lateral rooting. However, the AtIAA14-mediated pathway is not strictly required for callus initiation in the LR formation region in Arabidopsis. LRs can be initiated either through the AtIAA14-mediated or AtWOX11 mediated pathway in the Arabidopsis PR, therefore providing optional pathways for callus initiation. By contrast, OsIAA11 is strictly required for lateral rooting in the rice PR, meaning the OsIAA11 pathway is the only choice for callus initiation. Our study suggests that multiple pathways may converge to WOX5 activation during callus formation in different organs and different species. PMID- 29788451 TI - FDG-PET diagnoses of sporadic Creutzfeldt-Jakob disease: radiology-pathology correlation. PMID- 29788449 TI - Antisense transcriptional interference mediates condition-specific gene repression in budding yeast. AB - Pervasive transcription generates many unstable non-coding transcripts in budding yeast. The transcription of such noncoding RNAs, in particular antisense RNAs (asRNAs), has been shown in a few examples to repress the expression of the associated mRNAs. Yet, such mechanism is not known to commonly contribute to the regulation of a given class of genes. Using a mutant context that stabilized pervasive transcripts, we observed that the least expressed mRNAs during the exponential phase were associated with high levels of asRNAs. These asRNAs also overlapped their corresponding gene promoters with a much higher frequency than average. Interrupting antisense transcription of a subset of genes corresponding to quiescence-enriched mRNAs restored their expression. The underlying mechanism acts in cis and involves several chromatin modifiers. Our results convey that transcription interference represses up to 30% of the 590 least expressed genes, which includes 163 genes with quiescence-enriched mRNAs. We also found that pervasive transcripts constitute a higher fraction of the transcriptome in quiescence relative to the exponential phase, consistent with gene expression itself playing an important role to suppress pervasive transcription. Accordingly, the HIS1 asRNA, normally only present in quiescence, is expressed in exponential phase upon HIS1 mRNA transcription interruption. PMID- 29788453 TI - Myofascial Findings and Psychopathological Factors in Patients with Chronic Pelvic Pain Syndrome. AB - Objective: Chronic pelvic pain syndrome (CPPS) is a common pain condition with psychosocial and somatic symptoms. Myofascial findings and psychiatric comorbidities are frequent. Therefore, the aim of the study was to analyze myofascial and psychosocial aspects. Furthermore, the study focuses on correlations between these aspects and gender differences in this topic. Design: Cross-sectional study. Setting: Interdisciplinary outpatient clinic for patients with CPPS at the University Medical Centre Hamburg-Eppendorf, Germany. Methods: Participants underwent a multimodal diagnostic algorithm including physiotherapeutic assessment and psychotherapeutic evaluation. Those with a positive diagnosis of CPPS were included. Descriptive statistics were used to characterize and analyze the sample. Bivariate correlations were calculated for the association between myofascial findings and psychopathological symptoms. Results: A total of 187 patients (56.7% female, mean age +/- SD = 49.06 +/- 17.05 years) were included. Women had significantly higher numbers of tender (mean +/- SD = 17.53 +/- 9.58 vs 13.40 +/- 8.79, P = 0.003) and trigger points (mean +/- SD = 6.23 +/- 6.64 vs 4.09 +/- 7.15, P = 0.036). They had also significantly higher values in the PHQ-15 (mean +/- SD = 11.51 +/- 5.24 vs 9.28 +/- 5.49, P = 0.009) and the SF-MPQ (mean +/- SD = 17.84 +/- 8.95 vs 15.11 +/- 7.97, P = 0.041). Several significant correlations between myofascial findings and psychosocial factors exist. Conclusions: There might be a link between psychosomatic and myofascial aspects in CPPS; thus further studies are needed. Nevertheless, the results stress the urgent need of a multimodal treatment including physiotherapy and psychotherapy in these patients. PMID- 29788452 TI - Glutamine alleviates heat stress-induced impairment of intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers. AB - The aim of this study was to investigate the protective effect of glutamine (Gln) on the intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers exposed to high ambient temperature. Three-hundred-sixty 21 d-old Arbor Acres broilers (half male and half female) were randomly allocated to 4 treatment groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate, for 21 d. The 4 treatment groups were as follows: the control group, in which birds were kept in a thermoneutral room at 22 +/- 1 degrees C (no stress, NS; fed a basal diet); the heat stress group (36 +/- 1 degrees C for 10 h/d from 08:00 to 18:00 h and 22 +/- 1 degrees C for the remaining time, heat stress (HT); fed a basal diet); and heat stress + Gln group (0.5 and 1.0% Gln, respectively). Compared to the NS group, broilers in the HT group had lower villus height (P < 0.05), higher crypt depth (P < 0.05), higher D lactic acid and diamine oxidase (DAO) activity (P < 0.05), higher soluble intercellular adhesion molecule-1 (sICAM-1) concentration (P < 0.05), higher tumor necrosis factor (TNF)-alpha/interleukin (IL)-10 (P < 0.05), and lower tight junction protein expression levels (P < 0.05). Compared with birds in the HT, birds in the HT + Gln group exhibited increased villus height (P < 0.05), decreased D-lactate and DAO activity (P < 0.05), decreased sICAM-1 concentration (P < 0.05), and mediate the secretion of cytokines (P < 0.05), as well as increased zonula occludens-1 (ZO-1), claudin-1, and occludin mRNA expression levels (P < 0.05). In conclusion, these results indicate that supplementation with Gln was effective in partially ameliorating the adverse effects of heat stress on intestinal barrier function in broilers by promoting epithelial cell proliferation and renewal, modifying the function of the intestinal mucosa barrier, and regulating the secretion of cytokines. PMID- 29788455 TI - A 10-yr Analysis of Chronic Pelvic Pain and Chronic Opioid Therapy in the Women Veteran Population. AB - Introduction: Chronic pelvic pain (CPP) affects an estimated 30% of women Veterans. Previous research shows high rates of narcotic abuse in the women Veteran population. Narcotics are not recommended for the treatment of CPP. Understanding how CPP impacts narcotic prescribing in the women Veteran population is critical to addressing the public health crisis of opioid abuse. Our objective was to compare chronic opioid therapy (COT) prescribed 5 yr prior to and following CPP diagnosis and to identify predictors of COT as well as adverse events associated with COT. We choose to look at 10 yr of data because we thought this time period would provide unique insight into the longitudinal associations of CPP and COT and was available in the database. Materials and Methods: Women with non-cancer CPP were included for analyses from the Veteran's Affairs Corporate Database Warehouse. COT was defined as 90 d of opiates/calendar year for each of the 5 yr proceeding and following the diagnosis of CPP. Patient characteristics and potential variables influencing COT were collected. We compared baseline demographics between the women who received COT to the women who did not receive COT to find additional demographic predictors of COT in association with CPP. Multivariable analysis identified predictors of COT in this population of women with CPP. We utilized an interrupted time series analysis to understand the impact of the diagnosis of CPP on COT. Results: A total of 49,601 women met inclusion criteria with an average age of 40.1 +/- 11.5 yr; 37.3% self characterized as being a racial minority and 24% had a history of military sexual trauma. Chronic use increased significantly (p < 0.001) in the 5 yr preceding the diagnosis of CPP from 6.3% (n = 3124) of women at time -5 to 13.6% (n = 6746) at time 0. In the first year following the diagnosis of CPP, 16.8% (n = 8,333) of women with CPP met the criteria for COT (p < 0.001) and 15% (n = 7440) of women with CPP remained in the COT group for the remaining 5 yr following the diagnosis. On average women in the COT group had 250-292 d of opioids/year. When comparing women who received chronic narcotics following the diagnosis of CPP versus those who did not receive chronic narcotics, women who received COT were older, more likely to smoke and more frequently diagnosed with other pain conditions such as back pain, headaches, and fibromyalgia. (All p < 0.001). In the multivariable model, predictors of COT following CPP diagnosis included prior COT (OR = 10.0 (95% CI 9.4, 10.6), a positive history of military sexual trauma, smoking, and other chronic pain conditions. Conclusions: The distinct pattern of prescribing shown in this cohort may mean COT is prescribed for CPP and this prescribing pattern contributes to the adverse events associated with COT. As COT is not recommended for CPP, physicians need more education on the therapies available to help CPP patients. PMID- 29788454 TI - Variation in human chromosome 21 ribosomal RNA genes characterized by TAR cloning and long-read sequencing. AB - Despite the key role of the human ribosome in protein biosynthesis, little is known about the extent of sequence variation in ribosomal DNA (rDNA) or its pre rRNA and rRNA products. We recovered ribosomal DNA segments from a single human chromosome 21 using transformation-associated recombination (TAR) cloning in yeast. Accurate long-read sequencing of 13 isolates covering ~0.82 Mb of the chromosome 21 rDNA complement revealed substantial variation among tandem repeat rDNA copies, several palindromic structures and potential errors in the previous reference sequence. These clones revealed 101 variant positions in the 45S transcription unit and 235 in the intergenic spacer sequence. Approximately 60% of the 45S variants were confirmed in independent whole-genome or RNA-seq data, with 47 of these further observed in mature 18S/28S rRNA sequences. TAR cloning and long-read sequencing enabled the accurate reconstruction of multiple rDNA units and a new, high-quality 44 838 bp rDNA reference sequence, which we have annotated with variants detected from chromosome 21 of a single individual. The large number of variants observed reveal heterogeneity in human rDNA, opening up the possibility of corresponding variations in ribosome dynamics. PMID- 29788457 TI - The reliability of the clinical examination in predicting hemodynamic status in acute febrile illness in a tropical, resource-limited setting. AB - Introduction: The clinical examination alone is widely considered unreliable when assessing fluid responsiveness in critically ill patients. Little evidence exists on the performance of the clinical examination to predict other hemodynamic derangements or more complex hemodynamic states. Materials and methods: Patients with acute febrile illness were assessed on admission, both clinically and per non-invasive hemodynamic measurement. Correlations between clinical signs and hemodynamics patterns were analyzed, and the predictive capacity of the clinical signs was examined. Results: Seventy-one patients were included; the most common diagnoses were bacterial sepsis, scrub typhus and dengue infection. Correlations between clinical signs and hemodynamic parameters were only statistically significant for Cardiac Index (r=0.75, p-value <0.01), Systemic Vascular Resistance Index (r=0.79, p-value <0.01) and flow time corrected (r=0.44, p-value 0.03). When assessing the predictive accuracy of clinical signs, the model identified only 62% of hemodynamic states correctly, even less if there was more than one hemodynamic abnormality. Discussion: The clinical examination is not reliable to assess a patient's hemodynamic status in acute febrile illness. Fluid responsiveness, cardiodepression and more complex hemodynamic states are particularly easily missed. PMID- 29788456 TI - Kinact: a computational approach for predicting activating missense mutations in protein kinases. AB - Protein phosphorylation is tightly regulated due to its vital role in many cellular processes. While gain of function mutations leading to constitutive activation of protein kinases are known to be driver events of many cancers, the identification of these mutations has proven challenging. Here we present Kinact, a novel machine learning approach for predicting kinase activating missense mutations using information from sequence and structure. By adapting our graph based signatures, Kinact represents both structural and sequence information, which are used as evidence to train predictive models. We show the combination of structural and sequence features significantly improved the overall accuracy compared to considering either primary or tertiary structure alone, highlighting their complementarity. Kinact achieved a precision of 87% and 94% and Area Under ROC Curve of 0.89 and 0.92 on 10-fold cross-validation, and on blind tests, respectively, outperforming well established tools (P < 0.01). We further show that Kinact performs equally well on homology models built using templates with sequence identity as low as 33%. Kinact is freely available as a user-friendly web server at http://biosig.unimelb.edu.au/kinact/. PMID- 29788458 TI - Are globals for health, well-being and quality of life interchangeable? A mixed methods study in ankylosing spondylitis patients and controls. AB - Objective: Patients' experience of overall health is often assessed through a single-item global question. Here, we evaluated among patients with AS and population controls whether single-item questions on the constructs health, well being and quality of life (QoL) are interchangeable. Methods: In a mixed quantitative and qualitative approach, all subjects scored the three single-item globals on a numeric rating scale (0-10, best). Next, they indicated for each of the questions which aspects they had been considering when scoring. After forced reflection, globals were scored again. Dissimilarities in scores among constructs, between patients and controls, and before or after reflection were tested using mixed linear models. Themes identified per construct in the qualitative part were linked to the International Classification of Functioning, Disability and Health. The type of themes per construct was compared between patients and controls. Results: Sixty-eight AS patients and 84 controls completed the questionnaire. Patients scored significantly worse on each global than controls (mean 6.1-6.3 vs 7.2-7.6, all P < 0.01). Within groups, however, no significant differences in scores on each construct, or in scores before or after forced reflection were found. Health-related themes were relevant to each construct for patients, but were less relevant for controls when considering well being and QoL. Emotional functions were relevant to well-being in all participants. Social roles and financial situation were more frequently related to well-being and QoL in controls. Conclusion: While patients and controls identified content-related dissimilarities between the three constructs studied, this was not reflected in different scores of the globals. PMID- 29788460 TI - General Principles for Pial Synangiosis in Pediatric Moyamoya Patients: 2 Dimensional Operative Video. AB - Pial synangiosis is a method of indirect surgical revascularization developed at our institution for the treatment of moyamoya disease in pediatric patients. Similar surgical principles are employed in adult cases, often performed because of lack of an adequate donor vessel. Standardized protocols, including preadmission for preoperative intravenous hydration and aspirin administration, as well as intraoperative electroencephalography, are routinely employed to minimize operative risk. Perioperative heparinization is not required. The patient is positioned supine, without skull fixation, and the parietal branch of the superficial temporal artery is mapped with Doppler ultrasonography. The artery is microscopically dissected from distal to proximal, leaving a cuff of tissue around the vessel and elevated from the temporalis. The microscope is then removed, the temporalis is opened in a cruciate fashion, and a generous craniotomy is performed, with care to drill away from the exposed artery. The dura is then opened widely (preserving dural collateral vessels), followed by microscopic opening of the arachnoid in as many areas as possible. The donor vessel is then sutured to the pia with 10-0 nylons. The dural leaflets are laid on the brain (without suturing). Closure is completed with saline-soaked gelfoam, with fixation of the bone flap, and muscle reapproximation in the horizontal plane. The galea is closed, followed by the use of resorbable skin suture in pediatric patients. If indicated, the second hemisphere may be performed under the same anesthetic, reducing anesthetic risks and avoiding delayed revascularization. Postoperatively, the patient is awakened and transferred to the intensive care unit. PMID- 29788459 TI - Correlation between bone quality and microvascular damage in systemic sclerosis patients. AB - Objectives: SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, by trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Methods: Eighty-four SSc patients, 98 RA patients and 60 CNT, were studied. BMD (g/cm2) of the lumbar spine (L1-L4) was analysed by DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed. Results: A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA and BMD was found to be significantly lower than in the CNT (P < 0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (P < 0.001). TBS values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs active and early pattern, P < 0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (P = 0.238). Conclusion: The data obtained showed significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern). PMID- 29788462 TI - Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study. AB - Background: Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. Methods: We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by >=50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. Results: During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54 0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. Conclusions: The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis. PMID- 29788464 TI - Confucian Values as a Buffer Against Age-Based Stereotype Threat for Chinese Older Adults. AB - Objectives: Research has shown that stereotype threat can impair older adults' memory in Western cultures. We tested whether this also occurs for older adults from the East Asian Chinese culture. We also tested whether an intervention that highlighted Confucian principles would protect Chinese older adults from stereotype threat's detrimental effects. Method : Culturally-Chinese older adults residing in the United States completed a memory test either under age-based stereotype threat about cognitive decline or not. Prior to this, some participants were also reminded of Confucian traditions of filial piety and were assured these values had been transmitted to the younger generation. Results: Stereotype threat impaired Chinese older adults' memory performance. However, our intervention was effective in eliminating this deficit. When the Chinese participants were reminded of the Confucian principle of filial piety they did not exhibit stereotype threat effects. Discussion: Confirming that younger adults have an obligation to respect their elders can eliminate the social-evaluative pressure of stereotype threat for Chinese older adults. These findings are noteworthy since population aging is happening at an unprecedented pace in East Asia. Although our results suggest that stereotype threat can adversely affect older adults' cognitive performance in these societies, we also identify a culturally-based intervention to alleviate this impairment. PMID- 29788463 TI - E-Cigarette Science and Its Relevance for Regulatory Actions and Policy. PMID- 29788461 TI - Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis. AB - Objectives: This systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS. Methods: Cochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results. Results: Forty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11-25.2% (13% pooled in AS only). In PsA the range was 9.6-27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores). Conclusion: FM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions. PMID- 29788465 TI - Fact Finders for Patient Safety: Risk of Bleeding with Nonaspirin Nonsteroidal Anti-inflammatory Drugs Before Spine Procedures. PMID- 29788467 TI - Reply: An informed decision between cleavage-stage and blastocyst-stage transfers in IVF requires data on the transfers of frozen-thawed embryos. PMID- 29788466 TI - In vivo and in vitro evaluation of tissue colonization and survival capacity of Salmonella Oranienburg in laying hens. AB - Salmonella enterica serovar Oranienburg (SO) was linked to a human salmonellosis outbreak in the Midwest in 2015 and 2016 from consumption of eggs. However, unlike Salmonella enterica serovar Enteritidis (SE), little is known regarding the potential of SO to colonize in laying hens and contaminate eggs. We used in vivo and in vitro models to evaluate tissue colonization and survival capacity of SO. Twenty eight-week-old laying hens were each challenged with an oral dose of approximately 107 (n = 92) or 109 (n = 96) colony-forming units (CFU) in 1 mL saline and evaluated after 1, 2, and 4 wk. Standard microbiological methods with pre-enrichment and enrichment in selective media were used for detection of SO in tissues, egg shell wash, internal egg contents, and excreta. Peak colonization of spleen (86.9%), ovaries (31.6%), upper oviduct (15.8%), and lower oviduct (34.3%) was detected between 1 and 2 wk post-infection (pi), while at 4 wk SO was only recovered from spleens (25%). Salmonella enterica serovar Oranienburg was not recovered from internal egg contents. However, the presence of SO on egg shells was seen when there were traces of excreta. Shedding in excreta was found in 92 and 100% birds gavaged with 107 and 109 CFU at 2 wk pi, respectively. The invasion and proliferation of SO in ovarian granulosa cells (GC) was compared to that of SE, and while the invasion of SO into GC was comparable to SE, proliferation of SO was significantly lower (P < 0.05). The infective potential of SO was also assessed by enumerating survival in egg white over 4 wk under refrigerated conditions, resulting in 65% survival at 4 wk. Overall, our data suggested that SO infection in layers did not result in egg contamination via vertical transmission, and colonization of egg-forming tissues was limited to 2 wk pi. Survival within GC and egg white demonstrates the ability of SO to withstand antibacterial factors and the potential of SO to penetrate the yolk. PMID- 29788468 TI - CAVIAR: an R package for checking, displaying and processing wood-formation monitoring data. AB - In the last decade, the pervasive question of climate change impacts on forests has revived investigations on intra-annual dynamics of wood formation, involving disciplines such as plant ecology, tree physiology and dendrochronology. This resulted in the creation of many research groups working on this topic worldwide and a rapid increase in the number of studies and publications. Wood-formation monitoring studies are generally based on a common conceptual model describing xylem cell formation as the succession of four differentiation phases (cell division, cell enlargement, cell wall thickening and mature cells). They generally use the same sampling techniques, sample preparation methods and anatomical criteria to separate between differentiation zones and discriminate and count forming xylem cells, resulting in very similar raw data. However, the way these raw data are then processed, producing the elaborated data on which statistical analyses are performed, still remains quite specific to each individual study. Thereby, despite very similar raw data, wood-formation monitoring studies yield results that are still quite difficult to compare. CAVIAR-an R package specifically dedicated to the verification, visualization and manipulation of wood-formation-monitoring data-can help to improve this situation. Initially, CAVIAR was built to provide efficient algorithms to compute critical dates of wood formation phenology for conifers growing in temperate and cold environments. Recently, we developed it further to check, display and process wood-formation-monitoring data. Thanks to new and upgraded functions, raw data can now be consistently verified, standardized and modelled (using logistic regressions and Gompertz functions), in order to describe wood phenology and intra-annual dynamics of tree-ring formation. We believe that CAVIAR will help strengthening the science of wood formation dynamics by effectively contributing to the standardization of its concepts and methods, making thereby possible the comparison between data and results from different studies. PMID- 29788469 TI - Influences and Impact of Anxiety and Depression in the Setting of Inflammatory Bowel Disease. AB - Background: Individuals with inflammatory bowel disease (IBD) are at increased risk of developing anxiety or depression (A&D). Crohn's disease (CD) and ulcerative colitis (UC) with comorbid A&D are both more challenging to manage. IBD providers need to better understand the causes and impact of A&D in order to improve care for IBD patients. We sought to identify clinical factors that influence development of A&D and healthcare utilization in IBD. Methods: This is a retrospective analysis using an IBD natural history registry from a single tertiary care referral center. Presence of A&D was determined based upon responses to the Hospital Anxiety and Depression Scale. Demographic and clinical factors were abstracted to evaluate for significant associations. Results: Four hundred thirty-two IBD patients (132 UC, 256 CD, and 44 indeterminate colitis) were included in this study. One hundred ninety-two (44.4%) had anxiety or depression or both, and most were female (59.4%, P < 0.05). History of surgery (P < 0.05), female gender (P < 0.05), smoking (P < 0.05), and extra-intestinal manifestations (P < 0.01) were each independently predictive of A&D. Inflammatory bowel disease patients with A&D more often underwent imaging studies (53.6% vs 36.7%, P < 0.05), visited the ED (30.7% vs 20.8%, P < 0.05), or were hospitalized (31.7% vs 21.7%, P < 0.05). They were also more frequently prescribed corticosteroids (50.5% vs 36.7%, P < 0.01) and biologic medications (62.5% vs 51.3%, P < 0.05). Finally, they were more likely to have had at least 1 "no-show" (29.2% vs 16.7%, P < 0.01) and had a higher mean number of "no-shows" (0.69 +/- 0.1 vs 0.30 +/- 0.1, P < 0.01) over the study period. Discussion: Anxiety and depression are common in the setting of IBD and are strongly associated with surgical history, disease complications (including extra-intestinal manifestations), smoking, and female gender. Inflammatory bowel disease patients with A&D are also more likely to require therapy and to utilize healthcare resources. This study refines our understanding of A&D development and its impact in IBD and provides additional considerations for management in this setting. PMID- 29788470 TI - Opioids in intensive care unit (ICU): causal agent for sleep apnea, unmasking the undiagnosed sleep apnea or both in the ICU. PMID- 29788472 TI - Marchiafava-Bignami disease. PMID- 29788471 TI - Molecular mechanisms controlling plant growth during abiotic stress. PMID- 29788474 TI - Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency. AB - Background: Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. Methods: We enrolled 9 very early onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. Results: All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. Conclusions: We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001. PMID- 29788475 TI - Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men. AB - Background: Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case control study drawn from participants in three prospective cohort studies. Methods: Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Results: Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. Conclusions: This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men. PMID- 29788476 TI - The flutter-by effect: a comprehensive study of the fluttering cusps of the Perceval heart valve prosthesis. AB - OBJECTIVES: Sutureless aortic valve prostheses are gaining popularity due to the substantial reduction in cross-clamp time. In this study, we report our observations on the cusp-fluttering phenomenon of the Perceval bioprosthesis (LivaNova, London, UK) using a combination of technical and medical perspectives. METHODS: Between August 2014 and December 2016, a total of 108 patients (69% women) with a mean age of 78 years had aortic valve replacement using the Perceval bioprosthesis (34 combined procedures). All patients underwent transoesophageal echocardiography (TOE) intraoperatively. TOE was performed postoperatively to detect paravalvular leakage and to measure gradients, acceleration time, Doppler velocity indices (Vmax and LVOT/Vmax AV) and effective orifice area indices. In addition, a TOE examination was performed in 21 patients postoperatively. Data were collected retrospectively from our hospital database. RESULTS: The retrospective evaluation of the intraoperative TOE examinations revealed consistent fluttering in all patients with the Perceval bioprosthesis. The echocardiographic postoperative measurements showed a mean effective orifice area index of 0.91 +/- 0.12 cm2/m2. The overall mean pressure and peak pressure gradients were in a higher range (13.5 +/- 5.1 mmHg and 25.5 +/- 8.6 mmHg, respectively), whereas acceleration time (62.8 +/- 16.4 ms) and Doppler velocity indices (0.43 +/- 0.11) were within the normal range according to the American Society of Echocardiography or european association of echocardiography (EAE) guidelines. The 2-dimensional TOE in Motion Mode (M-Mode) that was performed in patients with elevated lactate dehydrogenase (LDH) levels revealed remarkable fluttering of the cusps of the Perceval bioprosthesis. CONCLUSIONS: In our study cohort, we observed the fluttering phenomenon in all patients who received the Perceval bioprosthesis, which was correlated with elevated LDH levels and higher pressure gradients. PMID- 29788477 TI - The relationship between sociodemographic factors and reporting having terminated a pregnancy among Ghanaian women: a population-based study. AB - Background: Pregnancy termination is an illegal medical procedure in Ghana and 88% of induced abortions are performed in unsafe conditions, thus recipients face an elevated risk of abortion-related complications. This study aims to explore the associations between sociodemographic factors and reporting having terminated a pregnancy among Ghanaian women. Methods: Logistic regression models were estimated using data from the 2014 Ghana Demographic and Health Survey (n=9396). ORs were computed for the associations between reporting pregnancy termination and select demographic and socio-economic factors. Results: Education level, employment status, financial status and marital status of women are significantly associated with reporting having terminated a pregnancy. Conclusions: Women who are employed, cohabit with a partner and are considered middle class or wealthy are more likely than their counterparts to report having terminated a pregnancy. Ghanaian women with intermediate levels of education are more likely than both their more- and less-educated counterparts to report having terminated a pregnancy. These findings highlight the need for the development of policies aimed at reducing unsafe abortions associated with unintended pregnancies. Specific recommendations include providing family planning education and outreach to high-risk groups to reduce unintended pregnancies and improving working conditions for expectant mothers, including provisions for paid maternity leave and job protection. PMID- 29788480 TI - How should adult patients with neurofibromatosis 1 be managed? PMID- 29788473 TI - Enhancing Psychosis-Spectrum Nosology Through an International Data Sharing Initiative. AB - The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation. PMID- 29788478 TI - A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair. AB - Fanconi Anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer. Of over 20 FA-linked genes, FANCJ uniquely encodes a DNA helicase and mutations are also associated with breast and ovarian cancer. fancj-/- cells are sensitive to DNA interstrand cross-linking (ICL) and replication fork stalling drugs. We delineated the molecular defects of two FA patient-derived FANCJ helicase domain mutations. FANCJ-R707C was compromised in dimerization and helicase processivity, whereas DNA unwinding by FANCJ-H396D was barely detectable. DNA binding and ATP hydrolysis was defective for both FANCJ R707C and FANCJ-H396D, the latter showing greater reduction. Expression of FANCJ R707C or FANCJ-H396D in fancj-/- cells failed to rescue cisplatin or mitomycin sensitivity. Live-cell imaging demonstrated a significantly compromised recruitment of FANCJ-R707C to laser-induced DNA damage. However, FANCJ-R707C expressed in fancj-/- cells conferred resistance to the DNA polymerase inhibitor aphidicolin, G-quadruplex ligand telomestatin, or DNA strand-breaker bleomycin, whereas FANCJ-H396D failed. Thus, a minimal threshold of FANCJ catalytic activity is required to overcome replication stress induced by aphidicolin or telomestatin, or to repair bleomycin-induced DNA breakage. These findings have implications for therapeutic strategies relying on DNA cross-link sensitivity or heightened replication stress characteristic of cancer cells. PMID- 29788482 TI - A telehealth system for automated diagnosis of asthma and chronical obstructive pulmonary disease. AB - This paper presents the development and real-time testing of an automated expert diagnostic telehealth system for the diagnosis of 2 respiratory diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD). The system utilizes Android, Java, MATLAB, and PHP technologies and consists of a spirometer, mobile application, and expert diagnostic system. To evaluate the effectiveness of the system, a prospective study was carried out in 3 remote primary healthcare institutions, and one hospital in Bosnia and Herzegovina healthcare system. During 6 months, 780 patients were assessed and diagnosed with an accuracy of 97.32%. The presented approach is simple to use and offers specialized consultations for patients in remote, rural, and isolated communities, as well as old and less physically mobile patients. While improving the quality of care delivered to patients, it was also found to be very beneficial in terms of healthcare. PMID- 29788479 TI - Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution. AB - Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections. PMID- 29788483 TI - Persisting Embryonal Infundibular Recess (PEIR): Two Case Reports and Systematic Literature Review. AB - Context: The persisting embryonal infundibular recess (PEIR) is a rare anomaly of the floor of the third ventricle with a debated pathogenesis. It can be a cause of misdiagnosis in the case of cystic lesions of the sellar and suprasellar area. Objective: To describe two recently evaluated cases and provide a systematic literature review. Evidence Acquisition and Case Descriptions: PEIR has been previously reported in six adult patients. Because in some cases it was associated with hydrocephalus and/or empty sella, a possible role of altered intracranial pressure in PEIR formation has been postulated. We evaluated two female patients, aged 34 and 50 years, referred to the Pituitary Surgery Clinic of the University of Brescia with the diagnosis of a sellar cyst and craniopharyngioma, respectively. Endocrine screening and visual field testing were normal. No signs of hydrocephalus or empty sella, as well as other indirect signs of intracranial hypertension, were visible on MRI scans. After a multidisciplinary reevaluation, diagnosis of PEIR was made in both cases. Both patients are followed but have not developed any disturbance related to the PEIR in the following 18 months. Conclusions: PEIR is a rare condition, probably unrecognized and the result of dysembriogenesis, which should be included in the differential diagnosis of cystic sellar lesions. Imaging features (funnel pituitary stalk and cyst in the sella) appear pathognomonic. A normal endocrine evaluation might help in the diagnosis and warrants conservative treatment. PMID- 29788484 TI - An E-liquid Flavor Wheel: A Shared Vocabulary based on Systematically Reviewing E liquid Flavor Classifications in Literature. AB - Introduction: E-liquids are available in a high variety of flavors. A systematic classification of e-liquid flavors is necessary to increase comparability of research results. In the food, alcohol and fragrance industry, flavors are classified using flavor wheels. We systematically reviewed literature on flavors related to e-cigarette use, to investigate how e-liquid flavors have been classified in research, and propose an e-liquid flavor wheel to classify e liquids based on marketing descriptions. Methods: The search was conducted in May 2017 using PubMed and Embase databases. Keywords included terms associated with e cigarettes, flavors, liking, learning, and wanting in articles. Results were independently screened and reviewed. Flavor categories used in the articles reviewed were extracted. Results: Searches yielded 386 unique articles of which 28 were included. Forty-three main flavor categories were reported in these articles (e.g., tobacco, menthol, mint, fruit, bakery/dessert, alcohol, nuts, spice, candy, coffee/tea, beverages, chocolate, sweet flavors, vanilla, unflavored). Flavor classifications of e-liquids in literature showed similarities and differences across studies. Our proposed e-liquid flavor wheel contains 13 main categories and 90 subcategories, which summarize flavor categories from literature to find a shared vocabulary. For classification of e liquids using our flavor wheel, marketing descriptions should be used. Conclusions: We have proposed a flavor wheel for classification of e-liquids. Further research is needed to test the flavor wheels' empirical value. Consistently classifying e-liquid flavors using our flavor wheel in research (e.g., experimental, marketing, or qualitative studies) minimizes interpretation differences and increases comparability of results. Implications: We reviewed e liquid flavors and flavor categories used in research. A large variation in the naming of flavor categories was found and e-liquid flavors were not consistently classified. We developed an e-liquid flavor wheel and provided a guideline for systematic classification of e-liquids based on marketing descriptions. Our flavor wheel summarizes e-liquid flavors and categories used in literature in order to create a shared vocabulary. Applying our flavor wheel in research on e liquids will improve data interpretation, increase comparability across studies, and support policy makers in developing rules for regulation of e-liquid flavors. PMID- 29788485 TI - Enzymatic synthesis of random sequences of RNA and RNA analogues by DNA polymerase theta mutants for the generation of aptamer libraries. AB - Nucleic acid aptamers, especially RNA, exhibit valuable advantages compared to protein therapeutics in terms of size, affinity and specificity. However, the synthesis of libraries of large random RNAs is still difficult and expensive. The engineering of polymerases able to directly generate these libraries has the potential to replace the chemical synthesis approach. Here, we start with a DNA polymerase that already displays a significant template-free nucleotidyltransferase activity, human DNA polymerase theta, and we mutate it based on the knowledge of its three-dimensional structure as well as previous mutational studies on members of the same polA family. One mutant exhibited a high tolerance towards ribonucleotides (NTPs) and displayed an efficient ribonucleotidyltransferase activity that resulted in the assembly of long RNA polymers. HPLC analysis and RNA sequencing of the products were used to quantify the incorporation of the four NTPs as a function of initial NTP concentrations and established the randomness of each generated nucleic acid sequence. The same mutant revealed a propensity to accept other modified nucleotides and to extend them in long fragments. Hence, this mutant can deliver random natural and modified RNA polymers libraries ready to use for SELEX, with custom lengths and balanced or unbalanced ratios. PMID- 29788486 TI - Two Endosomal NHX-Type Na+/H+ Antiporters are Involved in Auxin-Mediated Development in Arabidopsis thaliana. AB - In Arabidopsis thaliana, the endosomal-localized Na+/H+ antiporters NHX5 and NHX6 regulate ion and pH homeostasis and are important for plant growth and development. However, the mechanism by which these endosomal NHXs function in plant development is not well understood. Auxin modulates plant growth and development through the formation of concentration gradients in plant tissue to control cell division and expansion. Here, we identified a role for NHX5 and NHX6 in the establishment and maintenance of auxin gradients in embryo and root tissues. We observed developmental impairment and abnormal cell division in embryo and root tissues in the double knockout nhx5 nhx6, consistent with these tissues showing high expression of NHX5 and NHX6. Through confocal microscopy imaging with the DR5::GFP auxin reporter, we identify defects in the perception, accumulation and redistribution of auxin in nhx5 nhx6 cells. Furthermore, we find that the steady-state levels of the PIN-FORMED (PIN) auxin efflux carriers PIN1 and PIN2 are reduced in nhx5 nhx6 root cells. Our results demonstrate that NHX5 and NHX6 function in auxin-mediated plant development by maintaining PIN abundance at the plasma membrane, and provide new insight into the regulation of plant development by endosomal NHX antiporters. PMID- 29788488 TI - Surveillance of Mosquitoes (Diptera: Culicidae) in Southern Iowa, 2016. AB - The mosquito fauna of Iowa has been extensively investigated over several decades, providing a wealth of information regarding species distributions, relative abundance, temporal activity patterns, and identifying vectors of medical importance. However, these investigations have had unequal coverage, leaving the mosquito fauna in some parts of the state, including southern Iowa, largely uncharacterized. With the heightened public health threat of Zika virus in the summer of 2016, greater emphasis was placed on surveying for two potential Zika virus vectors: Aedes (Stegomyia) albopictus (Skuse) and Aedes (Stegomyia) aegypti (Linnaeus). Southern Iowa became an area of interest due to the range of Ae. Albopictus, potentially extending into this part of the state. Employing CO2 baited Centers for Disease Control and Prevention light traps and BG-Sentinel traps, our targeted trapping efforts in southern Iowa did not yield either Ae. albopictus or Ae. aegypti. However, the geographical expansion of our trapping efforts did lend valuable insights into the mosquito fauna of southern Iowa. Mosquito species such as Aedes atropalpus (Coquillett), Culex erraticus (Dyar and Knab), and several Psorophora species once presumed rare or uncommon in the state were found to be more prevalent in this ecologically diverse region, augmenting our understanding of mosquito distributions in the state. Moreover, these surveillance efforts established baseline data for continued monitoring of the potential introduction and spread of invasive mosquito species in Iowa as part of an integrated mosquito management program. PMID- 29788487 TI - The Effects of Metformin and Weight Loss on Biomarkers Associated With Breast Cancer Outcomes. AB - Background: This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 * 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided. Results: A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, >=80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to 1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG. Conclusions: As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality. PMID- 29788489 TI - Contribution of mental and physical disorders to disability in military personnel. AB - Background: Combat operations in Southwest Asia have exposed millions of military personnel to risk of mental disorders and physical injuries, including traumatic brain injury (TBI). The contribution of specific disorders to disability is, however, uncertain. Aims: To estimate the contributions of mental and physical health conditions to disability in military personnel. Methods: The sample consisted of military personnel who participated in the cross-sectional 2013 Canadian Forces Mental Health Survey. Disability was measured using the World Health Organization Disability Assessment. The International Classification of Functioning, Disability, and Health was used to classify participants with moderate/severe disability. Chronic mental disorders and physical conditions were measured by self-reported health professional diagnoses, and their contribution to disability was assessed using logistic regression and resulting population attributable fractions. Results: Data were collected from 6696 military members. The prevalence of moderate/severe disability was 10%. Mental disorders accounted for 27% (95% confidence interval [CI] 23-31%) and physical conditions 62% (95% CI 56-67%) of the burden of disability. Chronic musculoskeletal problems 33% (95% CI 26-39%), back problems 29% (95% CI 23-35%), mood disorders 16% (95% CI 11-19%) and post-traumatic stress disorder (PTSD) 9% (95% CI 5-12%) were the leading contributors to disability. After-effects of TBI accounted for only 3% (95% CI 1 4%) of disability. Mental and physical health interacted broadly, such that those with mental disorders experienced disproportionate disability in the presence of physical conditions. Conclusions: Chronic musculoskeletal conditions, back problems, mood disorders and PTSD are primary areas of focus in prevention and control of disability in military personnel. PMID- 29788490 TI - Effects of a protease and essential oils on growth performance, blood cell profiles, nutrient retention, ileal microbiota, excreta gas emission, and breast meat quality in broiler chicks. AB - A total of 360 Ross male broiler chicks (39.8 +/- 1.8 g) were used in a five week experiment to determine the effect of a protease and essential oils (EO) on growth performance, blood cell profile, nutrient retention, ileal microbiota, excreta gas emission, and breast meat quality in broiler chicks. Broiler chicks were randomly allotted to four dietary treatments with 15 birds/cage and six cages/treatment. Experimental treatments were arranged as a 2 * 2 factorial with two levels of protease (0 and 0.02%) and two levels of EO (0 and 0.03%). For days 8 to 21 and overall, body weight gain and the feed conversion ratio were better in broilers fed diets supplemented with protease (P < 0.05) than in those fed diets without protease supplementation. Protease and/or EO increased (P < 0.05) the total tract retention of dry matter, nitrogen, or gross energy, and decreased the excreta ammonia gas emission. In addition, there was a significant interaction between the protease and EO on total tract retention of nitrogen and excreta ammonia gas emission (P < 0.05). The density of ileal Lactobacillus increased and Escherichia coli decreased in broilers (P < 0.05) by the addition of EO to the diet. There were no significant differences in the measurements of breast meat quality and organ weight of broilers fed diets with protease or EO. In conclusion, diets with a combination of a protease and EO improved total tract retention of nitrogen and excreta ammonia gas emission in growing broiler chicks. PMID- 29788491 TI - Lowering the recurrence rate in pigmented villonodular synovitis: A series of 120 resections. AB - Objectives: Tenosynovial giant-cell tumour or pigmented villonodular synovitis is an aggressive synovial proliferative disease, with the knee joint being the most commonly affected joint. The mainstay of therapy is surgical resection. The aim of this study was to evaluate the main patient characteristics, treatment and outcomes in a large single-centre retrospective study, focusing on meticulous aggressive open surgical procedures. Methods: From 1996 through 2014, 122 surgical interventions were performed in 105 patients. All patients underwent open synovectomy and when the knee joint was affected, combined anterior and posterior synovectomy. Radiotherapy was applied in 2 patients, radiosynoviorthesis in 27 patients. Results: In histopathology, the diffuse type was seen in 66 (54%) lesions. Two patients were lost during follow-up. At a median follow-up time of 71 months (range: 13-238), 22 (18%) lesions recurred within a median of 18 months, >90% in the first 3 years. Out of those 22 recurrences, 9 (11%) were seen in primary disease and 13 (34%) were a second recurrence. After renewed resection, 6 (5%) out of the 120 resections had persistent tumour at the end of follow-up. Based on the number of patients with complete follow-up (n = 103), this represents 5.8%. Conclusion: In diffuse-type pigmented villonodular synovitis, total synovectomy might be difficult to achieve. As shown in our results and also in the literature, meticulous open resection, especially in difficult to approach areas such as the popliteal space, reduces local recurrence rates. External beam radiation is an option in prevention of otherwise non-operable local recurrences or in non-operable disease. PMID- 29788492 TI - Reply to 'Addressing the challenge of proper delineation of lymph node stations in modern radiotherapy for lung cancer'. PMID- 29788493 TI - How the Central American Seaway and an Ancient Northern Passage Affected Flatfish Diversification. AB - While the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the equator diverged during the closure of CAS, whereas those with a northern range diverged after this, hereby suggesting the existence of a postCAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions. PMID- 29788494 TI - Military Factors Associated with Smoking in Veterans. AB - Introduction: Given the high prevalence of smoking among Veterans and the economic, social, and clinical implications, it is important to understand the factors that contribute to smoking in order to focus efforts to mitigate these factors and improve smoking cessation efforts among Veterans. The availability of research on smoking in Veterans compared with civilians is limited given the military-specific differences in their life course. We aimed to identify military specific factors combined with sociodemographic factors for ever smoking and current smoking among Veterans to inform future interventions. Materials and Methods: We used data from the 2010 National Survey of Veterans, the most current, to analyze the association of sociodemographic and military-specific factors with ever versus never smoking, and current versus past smoking using multiple variable logistic regression models (IRB#4125). Results: Among 8,618 respondents, the proportions of current, past, and never smokers were 17%, 48%, and 34%, respectively. Sociodemographic factors associated with ever smoking were female gender, educational attainment of less than a bachelor's degree, and being divorced/separated/widowed. Military-specific factors associated with ever smoking were exposure to dead/dying/wounded soldiers during service, and past, current, and unsure enrollment in Veterans Affairs healthcare. Never smoking was associated with Hispanic ethnicity, income over $75,000, and reporting fair or poor health. Military factors associated with never smoking were presence of a service-connected disability and military service July 1964 or earlier (i.e., pre Vietnam). Among 5,652 ever smokers, sociodemographic factors associated with current smoking were age less than 65, being non-Hispanic black, educational attainment of less than a bachelor's degree, being divorced/separated/widowed, never married, and having no insurance. Factors associated with reduced likelihood of current smoking compared with past smoking included income >$41,000 and reporting fair or poor health. Military-specific variables associated with reduced likelihood of current smoking were service era of May 1975 or later (i.e., post-Vietnam) and 5 or more years of service. Conclusion: Military specific variables are associated with smoking behaviors among Veterans. Findings from this study that exposure to dead/dying/wounded soldiers, service era, duration of service, service-connected disability status, and enrollment in VA care all influence smoking in Veterans, can inform prevention and cessation efforts in part by encouraging alternative healthy habits or cessation techniques in subgroups of Veterans with particular military backgrounds. By assessing risk factors in this unique population future research can leverage these findings to determine mechanisms that help explain these associations. Identifying factors associated with smoking offers insights for smoking cessation and prevention interventions given the military experiences and increased smoking incidence among Veterans. PMID- 29788495 TI - Corrigendum to "The effects of dietary Selenium-yeast level on glutathione peroxidase activity, tissue Selenium content, growth performance, and carcass and meat quality of broilers". PMID- 29788496 TI - Distinguishing Between Convergent Evolution and Violation of the Molecular Clock for Three Taxa. AB - We give a non-technical introduction to convergence-divergence models, a new modeling approach for phylogenetic data that allows for the usual divergence of lineages after lineage-splitting but also allows for taxa to converge, i.e. become more similar over time. By examining the $3$-taxon case in some detail, we illustrate that phylogeneticists have been "spoiled" in the sense of not having to think about the structural parameters in their models by virtue of the strong assumption that evolution is tree-like. We show that there are not always good statistical reasons to prefer the usual class of tree-like models over more general convergence-divergence models. Specifically, we show many $3$-taxon data sets can be equally well explained by supposing violation of the molecular clock due to change in the rate of evolution along different edges, or by keeping the assumption of a constant rate of evolution but instead assuming that evolution is not a purely divergent process. Given the abundance of evidence that evolution is not strictly tree-like, our discussion is an illustration that as phylogeneticists we need to think clearly about the structural form of the models we use. For cases with four taxa, we show that there will be far greater ability to distinguish models with convergence from non-clock-like tree models. [Akaike information criterion; convergence-divergence models; distinguishability; identifiability; likelihood; molecular clock; phylogeny.]. PMID- 29788498 TI - CellAtlasSearch: a scalable search engine for single cells. AB - Owing to the advent of high throughput single cell transcriptomics, past few years have seen exponential growth in production of gene expression data. Recently efforts have been made by various research groups to homogenize and store single cell expression from a large number of studies. The true value of this ever increasing data deluge can be unlocked by making it searchable. To this end, we propose CellAtlasSearch, a novel search architecture for high dimensional expression data, which is massively parallel as well as light-weight, thus infinitely scalable. In CellAtlasSearch, we use a Graphical Processing Unit (GPU) friendly version of Locality Sensitive Hashing (LSH) for unmatched speedup in data processing and query. Currently, CellAtlasSearch features over 300 000 reference expression profiles including both bulk and single-cell data. It enables the user query individual single cell transcriptomes and finds matching samples from the database along with necessary meta information. CellAtlasSearch aims to assist researchers and clinicians in characterizing unannotated single cells. It also facilitates noise free, low dimensional representation of single cell expression profiles by projecting them on a wide variety of reference samples. The web-server is accessible at: http://www.cellatlassearch.com. PMID- 29788497 TI - A study of the focal adhesion kinase inhibitor GSK2256098 in patients with recurrent glioblastoma with evaluation of tumor penetration of [11C]GSK2256098. AB - Background: GSK2256098 is a novel oral focal adhesion kinase (FAK) inhibitor. Preclinical studies demonstrate growth inhibition in glioblastoma cell lines. However, rodent studies indicate limited blood-brain barrier (BBB) penetration. In this expansion cohort within a phase I study, the safety, tolerability, pharmacokinetics (PK), and clinical activity of GSK2256098 were evaluated in patients with recurrent glioblastoma. Biodistribution and kinetics of [11C]GSK2256098 were assessed in a substudy using positron-emission tomography (PET). Methods: Patients were treated with GSK2256098 until disease progression or withdrawal due to adverse events (AEs). Serial PK samples were collected on day 1. On a single day between days 9 and 20, patients received a microdose of intravenous [11C]GSK2256098 and were scanned with PET over 90 minutes with parallel PK sample collection. Response was assessed by MRI every 6 weeks. Results: Thirteen patients were treated in 3 dose cohorts (1000 mg, 750 mg, 500 mg; all dosed twice daily). The maximum tolerated dose was 1000 mg twice daily. Dose-limiting toxicities were related to cerebral edema. Treatment-related AEs (>25%) were diarrhea, fatigue, and nausea. Eight patients participated in the PET substudy, with [11C]GSK2256098 VT (volume of distribution) estimates of 0.9 in tumor tissue, 0.5 in surrounding T2 enhancing areas, and 0.4 in normal brain. Best response of stable disease was observed in 3 patients, including 1 patient on treatment for 11.3 months. Conclusions: GSK2256098 was tolerable in patients with relapsed glioblastoma. GSK2256098 crossed the BBB at low levels into normal brain, but at markedly higher levels into tumor, consistent with tumor-associated BBB disruption. Additional clinical trials of GSK2256098 are ongoing. PMID- 29788501 TI - Reply to "Clinical Examination in the Diagnosis of Myofascial Pain Syndrome; Methodological Issues on Validity and Reliability". PMID- 29788499 TI - Group I introns are widespread in archaea. AB - Group I catalytic introns have been found in bacterial, viral, organellar, and some eukaryotic genomes, but not in archaea. All known archaeal introns are bulge helix-bulge (BHB) introns, with the exception of a few group II introns. It has been proposed that BHB introns arose from extinct group I intron ancestors, much like eukaryotic spliceosomal introns are thought to have descended from group II introns. However, group I introns have little sequence conservation, making them difficult to detect with standard sequence similarity searches. Taking advantage of recent improvements in a computational homology search method that accounts for both conserved sequence and RNA secondary structure, we have identified 39 group I introns in a wide range of archaeal phyla, including examples of group I introns and BHB introns in the same host gene. PMID- 29788500 TI - Microvascular Dysfunction Following Multiwalled Carbon Nanotube Exposure Is Mediated by Thrombospondin-1 Receptor CD47. AB - Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation. Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 ug of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours postexposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT + MWCNT group compared with control (57 +/- 9 vs 90 +/- 2% relaxation), while CD47 KO animals showed no impairment (108 +/- 8% relaxation). Venular leukocyte adhesion and rolling increased by >2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT + MWCNT group. Lung and plasma NOx were reduced in the WT + MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47 + MWCNT group only. In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (*NO) signaling and promotes leukocyte endothelial interactions. Impaired *NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role. PMID- 29788502 TI - Are Fetal-Type Posterior Cerebral Arteries Associated With an Increased Risk of Posterior Communicating Artery Aneurysms? AB - BACKGROUND: Fetal-type posterior cerebral arteries (F-PCAs) might result in alterations in hemodynamic flow patterns and may predispose an individual to an increased risk of posterior communicating artery aneurysms (PCoAAs). OBJECTIVE: To determine the association between PCoAAs and the presence of ipsilateral F PCAs. METHODS: We retrospectively reviewed the radiographic findings from 185 patients harboring 199 PCoAAs that were treated at our institution between 2005 and 2015. Our study population consisted of 4 cohorts: (A) patients with 171 internal carotid arteries (ICAs) harboring unilateral PCoAAs; (B) 171 unaffected ICAs in the same patients from the first group; (C) 28 ICAs of 14 patients with bilateral PCoAAs; and (D) 180 ICAs of 90 patients with aneurysms in other locations. We then determined the presence of ipsilateral F-PCAs and recorded all aneurysm characteristics. RESULTS: Group A had the highest prevalence of F-PCAs (42%) compared to 19% in group B, 3% in group C, and 14% in group D (odds ratio A : B = 3.041; A : C = 19.626; and A : D = 4.308; P < .001). PCoAAs were associated with larger diameters of the posterior communicating arteries (median value 1.05 vs 0.86 mm; P = .001). The presence of F-PCAs was associated with larger sizes of the aneurysm necks (median value 3.3 vs 3.0 mm; P = .02). CONCLUSION: PCoAAs were associated with a higher prevalence of ipsilateral F-PCAs. This variant was associated with larger sizes of the aneurysm necks but was not associated with the sizes of the aneurysm domes or with their rupture statuses. PMID- 29788503 TI - Visual analogue scales for interstitial lung disease: a prospective validation study. AB - Rationale: Visual analogue scales (VAS) are simple symptom assessment tools which have not been validated in interstitial lung disease (ILD). Simple measures of ILD disease burden would be valuable for non-specialist clinicians monitoring disease away from ILD specialist centres. Objective: To validate VAS to assess change in dyspnoea, cough and fatigue in ILD, and to define the minimal clinically important difference (MCID) for change in these. Methods: 64 patients with ILD completed VAS for dyspnoea, cough and fatigue. Baseline King's Brief ILD questionnaire (K-BILD) scores, lung function and 6-minute walk test results were collected. Tests were repeated 3-6 months later, in addition to a 7-point Likert scale. The MCID was estimated using median change in VAS in patients who reported "small but just worthwhile change" in symptoms at follow-up. Methods were repeated in a validation cohort of 31 ILD patients to confirm findings. Results: VAS scores were significantly higher for patients who reported a "small but just worthwhile change" in symptoms versus "no change" or "not worthwhile change" (p < 0.01). The MCID for VAS Dyspnoea was estimated as 22.0mm and 14.5mm for VAS Fatigue. These results were reproducible in the validation cohort. Results were not significant for VAS Cough. Change in VAS Dyspnoea correlated with change in K BILD (r=-0.51, p < 0.01), forced vital capacity (r=-0.32, p = 0.01) and 6-minute walking distance (r=-0.37, p = 0.01). Conclusion: The VAS is valid for assessing change in dyspnoea and fatigue in ILD. The MCID is estimated as 22.0mm for dyspnoea and 14.5mm for fatigue. This could be used to monitor disease in settings away from ILD specialist review. PMID- 29788504 TI - Physiological response of broiler embryos to different incubator temperature profiles and maternal flock age during incubation. 1. Embryonic metabolism and day-old chick quality. AB - Broiler strain, maternal age, and incubation temperature influence embryo metabolism. Hatching eggs were obtained from young (Y; 28 to 34 wk, $?bar{?rm x}$ = 31.2 wk), mid (M; 36 to 45 wk, $?bar{?rm x}$ = 40.5 wk) and old (O; 49 to 54 wk, $?bar{?rm x}$ = 51.4 wk) Ross 708 (n = 88; Experiment 1) and Ross 308 [(n = 45; Experiment 2: (Y; 25 to 34 wk, $?bar{?rm x}$ = 30.5 wk), (M; 35 to 44 wk, $?bar{?rm x}$ = 40.2 wk), and (O; 49 to 54 wk, $?bar{?rm x}$ = 51.6 wk)] breeders. Eggs were stored for 2 to 4 d (18 degrees C, 73% RH), and incubated for 14 d at 37.5 degrees C and 56% RH. At 15 d (E15), 8 fertile eggs per flock age were incubated in individual metabolic chambers at 36.0, 36.5, 37.0, or 37.5 degrees C until E21.5. Each temperature was repeated one additional time. O2 consumption and CO2 production were used to calculate embryonic heat production (EHP). Embryo temperature was measured as eggshell temperature (EST). Initial egg weight was used as a covariate; significance was assessed at P < 0.05. In Ross 708, daily EHP tended to be higher in M and O than Y treatments at E16; EHP of M was higher than Y and O eggs at E18; M and O were higher than O eggs at E19. Incubation at 37.0 degrees C resulted in the highest EHP from E15 to E21, except at E17. Embryos at 37.5 degrees C had reduced EHP beyond E17. Daily EST from E15 to E21 was higher at 37.5 and 37.0 degrees C than at 36.0 and 36.5 degrees C. In Ross 308, daily EST was highest at 37.5 degrees C except at E20. Incubation temperature and EST were highly correlated (R2 = 0.90 to 0.89; P < 0.001). Ross 708 chicks were longer and hatched earlier at 37.0 degrees C than at 36.0 and 37.5 degrees C. EST and EHP increased with incubation temperature in Ross 708. In Ross 308, maternal flock age and incubation temperature did not impact EHP. However, EST was highest at 37.5 degrees C except at E20. Ross 708 was more sensitive to incubation temperature than Ross 308. PMID- 29788505 TI - MEASUREMENT OF NATURAL RADIONUCLIDES AND EXTERNAL RADIATION EXPOSURE DUE TO FLY ASH FROM A COAL-FIRED POWER PLANT (SPAIN) DEPOSITED ON SOILS. COMPARISON USING TWO DIFFERENT MEASUREMENT TECHNIQUES. AB - The evaluation of the radiological impact in soils due to the fly-ash ponds using both in situ techniques and laboratory based measurements is presented. In order to check the in situ techniques capabilities for monitoring this type of industries, a comparison between both techniques was performed. A characterization of external radiation exposure in the fly-ash pond and in its surrounding soils was made. The associated external radiological hazard due to the fly-ash pond has been evaluated. In situ techniques could be used to determine the radiological impact on soils due to fly-ash deposition, but its use could be limited due to the associated uncertainties. PMID- 29788506 TI - Experiences and career intentions of combat-deployed UK military personnel. AB - Background: Most studies of the psychological impact of military deployment focus on the negative and traumatic aspects. Less is known about the full range of deployment experiences nor how these may impact on career intentions. Aims: To examine subjective operational experiences and career intentions in deployed UK military personnel using data gathered toward the end of an operational deployment. Methods: Data were gathered during deployment in Iraq and Afghanistan. A self-report survey collected data on sociodemographic, operational and military factors. Respondents provided their strength of agreement or disagreement with six potentially positive deployment experiences and their endorsement or rejection of six possible career intentions. Two mental health measures assessed symptoms of common mental disorder and post-traumatic stress disorder. Results: Responses were 681 in Iran 2009 (100% response rate); 1421 in Afghanistan in 2010 (100%), 1362 in 2011 (96%) and 860 in 2015 (91%). Five of the potentially positive outcomes were endorsed by >50% of the sample: confidence about remaining healthy after returning home, pride in accomplishments, increased confidence in abilities, improved unit cohesion and experiencing a positive life effect. Ninety per cent of respondents planned to continue in service after returning home. Fewer positive deployment experiences, poorer mental health, lesser unit cohesion and more negative impressions of leadership were significantly associated with intention to leave service. Conclusions: Contrary to the popular belief that UK military personnel deployed to Iraq or Afghanistan experience negative outcomes, this paper shows that deployment can be a positive experience for a substantial majority of deployed personnel. PMID- 29788507 TI - Obesity and health in the North American Fire Service: research points the way to positive culture change. PMID- 29788508 TI - Governments must catch up with workplace non-communicable disease prevention. PMID- 29788509 TI - Comparison of dynamic change of egg selenium deposition after feeding sodium selenite or selenium-enriched yeast. AB - The aim of this study was to compare the dynamic change of egg selenium (Se) deposition after sodium selenite (SS) or selenium-enriched yeast (SY) supplementation for 1, 3, 5, 7, 14, 21, 28, 56, and 84 d. A total of 576 32-wk old Hy-Line Brown laying hens were randomly assigned to 3 groups (192 laying hens per group) with 6 replicates, and fed a basal diet (without Se supplementation) or basal diets with 0.3 mg/kg of Se from SS or 0.3 mg/kg of Se from SY, respectively. The results showed that the Se concentrations in the eggs from hens fed a SY-supplemented diet were significantly higher (P < 0.001) than those from hens fed a SS-supplemented diet or a basal diet after 3 d. And the Se concentrations in the eggs from hens fed a SS-supplemented diet were significantly higher (P < 0.001) than those from hens fed a basal diet after 14 d. There was a positive linear and quadratic correlation between Se concentrations in the eggs from hens fed a SY-supplemented diet (r2 = 0.782, P < 0.001; r2 = 0.837, P < 0.001) or SS-supplemented diet (r2 = 0.355, P < 0.001; r2 = 0.413, P < 0.001) and number of feeding days. The Se concentrations in the breasts from hens fed a SY-supplemented diet were 126.98% higher (P < 0.001) than those from hens fed a SS-supplemented diet, and were 299.44% higher (P < 0.001) than those from hens fed a basal diet after the 84-d feeding period. In conclusion, the dietary Se was gradually transferred into eggs with the extension of the experimental duration. The deposition rate of Se in the eggs from hens fed a SY-supplemented diet was much more rapid than that from hens fed a SS supplemented diet, and the organic Se from SY had higher bioavailability as compared to inorganic Se from SS. PMID- 29788510 TI - Predicting Drug-Induced Liver Injury Using Ensemble Learning Methods and Molecular Fingerprints. AB - Drug-induced liver injury (DILI) is a major safety concern in the drug development process, and various methods have been proposed to predict the hepatotoxicity of compounds during the early stages of drug trials. In this study, we developed an ensemble model using 3 machine learning algorithms and 12 molecular fingerprints from a dataset containing 1241 diverse compounds. The ensemble model achieved an average accuracy of 71.1 +/- 2.6%, sensitivity (SE) of 79.9 +/- 3.6%, specificity (SP) of 60.3 +/- 4.8%, and area under the receiver operating characteristic curve (AUC) of 0.764 +/- 0.026 in 5-fold cross validation and an accuracy of 84.3%, SE of 86.9%, SP of 75.4%, and AUC of 0.904 in an external validation dataset of 286 compounds collected from the Liver Toxicity Knowledge Base. Compared with previous methods, the ensemble model achieved relatively high accuracy and SE. We also identified several substructures related to DILI. In addition, we provide a web server offering access to our models (http://ccsipb.lnu.edu.cn/toxicity/HepatoPred-EL/). PMID- 29788511 TI - Training Effects of Alternated and Pulsed Currents on the Quadriceps Muscles of Athletes. AB - The aim of the study was to evaluate the effects of 6 weeks training with different neuromuscular electrical stimulation (NMES) currents (medium alternated and low-frequency pulsed current) on muscle architecture and neuromuscular performance of competitive athletes. A double-blind controlled and randomized experimental study was carried out with 33 athletes (22.2+/-2.6 yrs, 74.7+/-9.8 kg, 176.8+/-6.0 cm), divided into 3 groups: mid-frequency current (MF, n=12), pulsed current (PC, n=11) and the control group (CG, n=10). Quadriceps maximal voluntary peak torque (PT) and corresponding vastus lateralis electromyographic activity, evoked torque (PT-NMES), vastus lateralis muscle thickness, fascicle length, pennation angle, and level of discomfort were assessed before and after the interventions. NMES training was performed 3 times per week and consisted of 18 sessions, 15 min/session, 6 s duration in each contraction interspersed with 18 s rest. After the training period, muscle thickness increased in the MF and PC groups (p<0.05). PT-NMES increased only in the PC group (p<0.05). All currents produced similar levels of discomfort (p>0.05). Quadriceps NMES training applied through alternated or pulsed currents produced similar effects in architecture and neuromuscular performance in competitive athletes. PMID- 29788512 TI - Adequacy of Fixed-Dose Heparin Infusions for Venous Thromboembolism Prevention after Microsurgical Procedures. AB - BACKGROUND: In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real time, anti-factor Xa (aFXa) level driven heparin dose adjustments. METHODS: This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE. RESULTS: Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%. CONCLUSIONS: Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12 units/kg/h deserve future study in patients undergoing microsurgical procedures to increase the proportion of patients receiving adequate VTE prophylaxis. PMID- 29788513 TI - [Granular Cell Tumor of the Lung - a Visual Diagnosis on Bronchoscopy?] AB - A 38 years old patient presented with a progressive reduction of his general condition and weight loss. Chest imaging revealed consolidations and cavities suggesting a mycobacterial infection. For further diagnosis, a bronchoscopy was performed. In fact, a nontuberculous mycobacterial infection was found. As an incidental finding, we saw a white polypoid tumor in the middle lobe bronchus. The histology of this tumor revealed a granular cell tumor (GCT). The GCT is a rare tumor entity which occurs at different anatomical locations. In the lungs, the GCT may become symptomatic as it can cause bronchial obstruction. In chest imaging, it can manifest as infiltration, atelectasis or nodule. Likewise, GCT can be found as an incidental finding in bronchoscopy. First choice treatment is surgical resection of the tumor. PMID- 29788514 TI - Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy. AB - BACKGROUND: Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non malignant diseases. METHODS: A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications. RESULTS: During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 - 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %. CONCLUSIONS: EBUS TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA. PMID- 29788516 TI - ? PMID- 29788517 TI - ? PMID- 29788515 TI - [Survey of Specialist Pulmonary Medicine Health Care Structures for Patients with Interstitial Lung Disease in Nordrhein-Westfalen, Germany - A Pilot Project of the Western German Respiratory Society (WdGP)]. AB - AIM OF THE STUDY: Survey of specialist pulmonary medicine health care structures for patients with interstitial lung disease (ILD) in Nordrhein-Westfalen, Germany. METHODS: The Western German Respiratory Society initiated a voluntary registration of ILD expert centers. Structural quality and processes were evaluated by questionnaire. RESULTS: 49 centers were registered, 46 allowed analysis of their center data (15 pulmonology specialist practices, 34 hospital pulmonology departments). Specialist practices saw a median of 360 ILD patients per year (26 % first diagnosis), hospital departments a median of 105 ILD patients per year (63 % first diagnosis). 10 centers diagnose more than 100 new ILD cases per year. Specialist practices report median 50 bronchoscopies per year, hospital departments median 1396. 78 % of the centers participate in a multidisciplinary ILD case conference. CONCLUSION: Several ILD expert centers were identified in Nordrhein-Westfalen. Outpatient care mainly involves the monitoring of ILD patients, inpatient services focus on complex initial diagnostics or cases with unusual disease behaviour. ILD centers meeting regional health care needs should be supported in their development. PMID- 29788518 TI - ? PMID- 29788519 TI - ? PMID- 29788520 TI - ? PMID- 29788521 TI - ? PMID- 29788522 TI - ? PMID- 29788524 TI - ? PMID- 29788523 TI - ? PMID- 29788525 TI - ? PMID- 29788526 TI - ? PMID- 29788527 TI - ? PMID- 29788528 TI - [Recurrent Tarsal Tumor in a Patient with Polyposis coli]. PMID- 29788529 TI - [A web-based Colour Vision Test as a Tool for Qualitative Evaluation of Pseudoisochromatic Pfluger Trident Colour Plates]. AB - BACKGROUND: Pseudoisochromatic colour plates are constructed according to specific principles. They can be very different in quality. To check the diagnostic quality, they have to be tested on a large number of subjects, but this procedure is can be tedious and expensive. Therefore, the use of a standardised web-based test is recommended. METHODS: Eight Pfluger trident colour plates (including 1 demo plate) according to the Velhagen edition of 1980 were digitised and inserted into a web-based colour vision test (www.color-vision test.info). After visual display calibration and 2 demonstrations of the demo plate (#1) to introduce the test procedure, 7 red-green colour plates (#3, 4, 10, 11, 12, 13, 16) were presented in a randomised order in 3 different randomised positions each for 10 seconds. The user had to specify the opening of the Pfluger trident by a mouse click or arrow keys. RESULTS: 6360 evaluations of all plates from 2120 randomised subjects were included. Without error, the detection rates of the plates were between 72.2% (plate #3) and 90.7% (plate #16; n = 6360). With an error number of 7 errors per test, the detection rates of the plates were between 21.6% (plate #3) and 67.7% (plate #16; n = 1556). If an error number of 14 errors was used, the detection rates of the plates were between 10.9% (plate #11) and 40.1% (plate #16; n = 606). Plate #16 showed the highest detection rate at zero error number as well as at the 7 and 14 error limit. The diagnostic quality of this plate was low. The colourimetric data were improved. The detection rate was then significantly lower. CONCLUSIONS: The differences in quality of pseudoisochromatic Pfluger trident colour plates can be tested without great effort using a web-based test. Optimisation of a poor quality colour plate can then be carried out. PMID- 29788530 TI - Need For Long-Term Care in Children is Increasingly Caused by Disorders of Psychological Development. Changes in the Care Causing Diagnoses According to German Social Code (SGB XI) Between 2009-2014. AB - AIM OF THE STUDY: There is an ongoing discussion on the increasing number of children with mental and developmental disorders, with some even needing long term care according to the German Social Code XI. This study was performed to identify the main diagnoses justifying such care in children and to analyse their prevalence over time. METHODS: The diagnoses justifying long-term care were evaluated using care assessments of Bavarian children and adolescents between 2009 to 2014 by the medical service of statutory health insurance. RESULTS: Over the years investigated, the percentage of assessments due to a mental and behavioural disorder rose significantly from 36.2 to 42.2%. Since 2012, the most common diagnose changed from Down's syndrome to pervasive developmental disorders with marked increase of also mixed specific developmental disorders. In new applications for nursing insurance services the proportion of pervasive developmental disorders rose gradually from 151 in 2010 to 254 in 2014. During the whole period of time, the overall care dependency in children seemed to be stable. CONCLUSIONS: These observations might rather be influenced by altered awareness of health and illness, increasing readiness to seek help with psychological or developmental impairments as well as changed diagnostic criteria than by a steady increase in affected individuals. PMID- 29788531 TI - [Insufficient Preparation of Ambulatory Physicians for Ebola Virus Disease in Germany]. AB - BACKGROUND: Globalization and climate change increase the likelihood of a global spread of high consequence infectious diseases. OBJECTIVES: We analyzed how outpatient physicians in Germany were prepared to recognize and handle potential Ebola virus-infected patients during the recent Ebola outbreak in West Africa. MATERIALS AND METHODS: Outpatient physicians participated in 2 anonymous surveys (n=166 and 129, respectively) and were asked, among others, about their knowledge of Ebola virus disease, their subjective perception of their own knowledge and the practical implementation in their daily routine. This was compared to a minimum standard defined by 14 members of the German "Permanent Working Group of Competence and Treatment Centres for high consequence infectious diseases" (STAKOB). RESULTS: The Ebola virus-specific knowledge of participants was significantly inferior compared to the defined minimum standard. Of 8 factual questions, an average of merely 5 was answered correctly. The physicians' subjective perception of knowledge presented as 'little'. Although 56% of participants indicated that they had received standard operation procedures, 64% had not implemented them into their daily routine. Merely 22% of surveyed medical doctors participated in Ebola virus-specific education programs. Yet participation led to a significantly better subjective knowledge perception. CONCLUSIONS: Contrary to the official assessment that Germany is well prepared for high consequence infectious diseases, this study suggests that there are deficits in this area. Despite the abundance of information about Ebola virus disease, preparation of outpatient physicians in Germany was inadequate. Yet nearly half of the participants indicated the potential risk of occurrence as 'likely' or 'very likely'. The presented data show the different consequences to be drawn regarding potential future crises and further research. PMID- 29788532 TI - Effect of Adding Magnesium Sulphate to Epidural Bupivacaine and Morphine on Post Thoracotomy Pain Management: A Randomized, Double-Blind, Clinical Trial. AB - Post-thoracotomy pain is very severe and may cause pulmonary complications. Thoracic epidural analgesia can greatly decrease the pain experience and its consequences. However, finding new methods to decrease the amount of administered opioids is an important issue of research. We aimed to evaluate the effect of adding epidural magnesium sulphate to bupivacaine and morphine on pain control and the amount of opioid consumption after thoracotomy. Eighty patients undergoing thoracotomy at a tertiary cardiothoracic referral centre were enrolled in a randomized, double-blind trial. Patients were randomly allocated to two groups. Bupivacaine (12.5 mg) and morphine (2 mg) were administered epidurally to all patients at the end of operation. Patients in the magnesium (Mg) group received epidural magnesium sulphate (50 mg), and patients in the control (C) group received normal saline as an adjuvant. Visual analogue scale (VAS) score and the amount of morphine consumption were measured during 24 hr post-operation. Thirty-nine patients in the Mg group and 41 patients in the C group completed the study. Patients in the Mg group had significantly less VAS score at recovery time (p < 0.05), 2 hr (p < 0.01) and 4 hr (p < 0.05) after surgery. The patient controlled analgesia pump was started earlier in the C group than in the Mg group (p < 0.05). The amount of morphine needed in the Mg group was significantly lower than in the C group (5.64 +/- 1.69 mg/24 hr versus 8.44 +/- 3.98 mg/24 hr; p < 0.001). Pruritus was seen in the C group (9.7%) and absent in the Mg group (p < 0.05). Co-administration of magnesium sulphate with bupivacaine and morphine for thoracic epidural analgesia after thoracotomy leads to a reduction in post operative pain score and the need for opioid administration. PMID- 29788534 TI - Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers. AB - CONTEXT: The 68 Ga-labelled somatostatin analogues (68 Ga-DOTA-SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68 Ga-DOTA-SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and pulmonary neuroendocrine tumours. OBJECTIVE: The aim of our prospective study was to perform head-to-head comparison between 68 Ga DOTATATE PET/CT and standard imaging work-up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography. DESIGN: In this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP-NETs. RESULTS: Thirty-two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron-specific enolase). 68 Ga-DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P = .074). The missed tumours on 68 Ga-DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68 Ga-DOTATATE PET/CT and SRS. Overall, 68 Ga-DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68 Ga-DOTATATE and SRS, respectively). CONCLUSION: Our study shows that 68 Ga-DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco-abdominopelvic CT on region-based analysis. 68 Ga-DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome. PMID- 29788535 TI - Cyp2a5 Promoter-based Gene Reporter Assay: A Novel Design of Cell-based Bioassay for Toxicity Prediction. AB - The murine cytochrome P450 2a5 (Cyp2a5) gene is regulated by complex interactions of various stress-activated transcription factors (TFs). Elevated Cyp2a5 transcription under chemical-induced stress conditions is achieved by interplay between the various TFs - including as aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2) - at the 'stress responding' cluster of response elements on the Cyp2a5 promoter, as well as through mRNA stabilization mediated by interaction of the stress-activated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with the 3'-UTR of the CYP2A5 mRNA. We designed a unique toxicity pathway-based reporter assay to include regulatory regions from both the 5' and the 3' untranslated regions of Cyp2a5 in a luciferase reporter plasmid to reflect in vivo responses to chemical insult. Human breast cancer MCF-7 cells were stably transfected with pGL4.38 Cyp2a5_Wt3k (wild-type) or mutant - pGL4.38-Cyp2a5_StREMut and pGL4.38 Cyp2a5_XREMut - reporter gene to monitor chemical-induced cellular response mediated by AhR and Nrf2 signalling. The recombinant cells were treated with representative of AhR agonist, polycyclic aromatic hydrocarbons, brominated flame retardant, fluorosurfactant, aromatic organic compound and metal, to determine the sensitivity of the Cyp2a5 promoter-based gene reporter assays to chemical insults by measuring the LC50 and EC50 of the respective chemicals. The three assays are sensitive to sublethal cellular responses of chemicals, which is an ideal feature for toxicity pathway-based bioassay for toxicity prediction. The wild-type reporter responded well to chemicals that activate crosstalk between the AhR and Nrf2, whilst the mutant reporters effectively gauge cellular response driven by either Nrf2/StRE or AhR/XRE signalling. Thus, the three gene reporter assays could be used tandemly to determine the predominant toxicity pathway of a given compound. PMID- 29788533 TI - Weight bias internalization and health: a systematic review. AB - A robust literature has documented the negative health effects of being the target of weight bias. Weight bias internalization (WBI) occurs when individuals apply negative weight stereotypes to themselves and self-derogate because of their body weight. Compared with experiences of weight bias, less is known about the relationship between WBI and mental and physical health, although more literature on this topic has emerged in recent years. The current systematic review identified 74 studies assessing the relationship between WBI and health and interventions designed to reduce WBI and improve health. Over half of identified studies were published from 2016 to 2017. Results showed strong, negative relationships between WBI and mental health outcomes. Fewer studies have examined the relationship between WBI and physical health, and results were less consistent. Key directions for future research are highlighted, including the need for prospective and experimental studies with greater sample diversity. PMID- 29788536 TI - Community disassembly under global change: Evidence in favor of the stress dominance hypothesis. AB - Ecological theory suggests that communities are not random combinations of species but rather the results of community assembly processes filtering and sorting species that are able to coexist together. To date, such processes (i.e., assembly rules) have been inferred from observed spatial patterns of biodiversity combined with null model approaches, but relatively few attempts have been made to assess how these processes may be changing through time. Specifically, in the context of the ongoing biodiversity crisis and global change, understanding how processes shaping communities may be changing and identifying the potential drivers underlying these changes become increasingly critical. Here, we used time series of 460 French freshwater fish communities and assessed both functional and phylogenetic diversity patterns to determine the relative importance of two key assembly rules (i.e., habitat filtering and limiting similarity) in shaping these communities over the last two decades. We aimed to (a) describe the temporal changes in both functional and phylogenetic diversity patterns, (b) determine to what extent temporal changes in processes inferred through the use of standardized diversity indices were congruent, and (c) test the relationships between the dynamics of assembly rules and both climatic and biotic drivers. Our results revealed that habitat filtering, although already largely predominant over limiting similarity, became more widespread over time. We also highlighted that phylogenetic and trait-based approaches offered complementary information about temporal changes in assembly rules. Finally, we found that increased environmental harshness over the study period (especially higher seasonality of temperature) led to an increase in habitat filtering and that biological invasions increased functional redundancy within communities. Overall, these findings underlie the need to develop temporal perspectives in community assembly studies, as understanding ongoing temporal changes could provide a better vision about the way communities could respond to future global changes. PMID- 29788537 TI - Ten years of medical education registrars: Value added? AB - OBJECTIVE: There is a paucity of any long-term follow up of trainees' career pathways or organisational outcomes from medical education registrar posts in emergency medicine training. We report on the experience of a selected group of medical education trainees during and subsequent to their post and reflect on the value added to emergency medical education at three institutions. METHODS: We conducted an online survey study, examining quantitative outcomes and qualitative reflections, of emergency physicians who had previously undertaken a medical education registrar post. Descriptive statistics were used to summarise responses to Likert items. The authors independently analysed and interpreted the reflective responses to identify key themes and sub-themes. RESULTS: Nineteen of 21 surveys were completed. Most respondents were in formal educational roles, in addition to clinical practice. The thematic analysis revealed that the medical education registrar experience, and the subsequent contribution of these trainees to medical education, is significantly shaped by external factors. These include the extent of faculty support, and the value placed on medical education by hospitals/departments/leaders. Acquisition of knowledge and skills in medical education was only part of a broader developmental journey and transitioning of identity for the trainees. CONCLUSIONS: Our findings suggest that medical education trainees in emergency medicine progress to educational roles, and most respondents attribute their career progression to the medical education training experience. We recommend that medical education registrar programmes need to be valued within the clinical service, supported by faculty and a 'community of practice', to support trainees' transition to clinician educator leadership roles. PMID- 29788538 TI - Hepatitis E virus in South America: The current scenario. AB - Hepatitis E virus (HEV) is one of the most frequent causes of acute viral hepatitis of enteric transmission worldwide. In South America the overall epidemiology has been little studied, and the burden of the disease remains largely unknown. A research of all scientific articles about HEV circulation in South America until November 2017 was carried out. Human seroprevalences of HEV varied according to the studied population: blood donors presented prevalence rates ranging from 1.8% to 9.8%, while reports from HIV-infected individuals, transplant recipients and patients on hemodialysis showed higher prevalence rates. Only 2 cases of chronic hepatitis in solid-organ transplant patients from Argentina and Brazil have been described. Detection of HEV in the swine population is widely prevalent in the region. Anti-HEV antibodies have also been recently documented in wild boars from Uruguay. Although scarce, studies focused on environmental and food HEV detection have shown viral presence in these kind of samples, highlighting possible transmission sources of HEV in the continent. HEV genotype 3 was the most frequently detected in the region, with HEV genotype 1 detected only in Venezuela and Uruguay. HEV is widely distributed throughout South America, producing sporadic cases of acute hepatitis, but as a possible agent of chronic hepatitis. Finding the virus in humans, animals, environmental samples and food, show that it can be transmitted through many sources, alerting local governments and health systems to improve diagnosis and for the implementation of preventive measures. PMID- 29788539 TI - Responses of Primula vulgaris to light quality in the maternal and germination environments. AB - In the model species Arabidopsis thaliana phytochromes mediate dormancy and germination responses to seasonal cues experienced during seed maturation on the maternal plants. However, the effect of the maternal light environment on seed germination in native wild species has not been well studied. This is particularly important given its practical application in the context of environmental restoration, when there can be marked changes in the canopy. Plants of Primula vulgaris were grown in the field over two vegetative seasons under four shading treatments from low to high ratio of red to far-red light (R:FR). Leaf and seed traits were assessed in response to the light treatments. The germination of seeds from these four maternal environments (pre-dispersal) was investigated at seven light and five temperature treatments (post-dispersal). Thinner leaves, larger leaf area and greater chlorophyll content were found in plants growing in reduced R:FR. Shading in the maternal environment led to increased seed size and yield, although the conditions experienced by the maternal plants had no effect on seed germination. Seeds responded strongly to the cues experienced in their immediate germination environment. Germination was always enhanced under higher R:FR conditions. The observed phenotypic trait variation plays a major role in the ability of P. vulgaris to grow in a wide range of light conditions. However, the increased germination capacity in response to a higher R:FR for all maternal environments suggests potential for seedling establishment under vegetative shade only in the presence of canopy gaps. PMID- 29788540 TI - Unusual presentation of calcific tendinitis of the iliopsoas tendon in a 28-year old female. PMID- 29788541 TI - Increase in incidental detection of thyroid cancer in Osaka, Japan. AB - Using Osaka Cancer Registry data, we examined age-specific and age-adjusted incidence rates of thyroid cancer according to the route of thyroid cancer detection from 1992 to 2012. The detection routes were categorized into "symptomatic" and "incidental detection." Age-specific incidence rates of incidentally-detected thyroid cancer consistently increased during the study period, especially after 2001, for all sex and age groups other than childhood. The rate of symptomatic thyroid cancer did not largely differ among groups. Age adjusted incidence rates of symptomatic thyroid cancer were around 1.5 and 4.5 per 100 000 among men and women, respectively. The rate of incidentally-detected thyroid cancer increased from 0.1 and 0.1 per 100 000 person-years among men and women in 1992-1994 to 2.0 and 4.9, respectively, in 2010-2012. Age-adjusted mortality rates among both sexes during the study period leveled off. This finding suggests that the thyroid cancer incidence rate in Osaka increased with incidental detection. We need to continue careful monitoring to confirm these findings. PMID- 29788542 TI - Accuracy of visual inspection performed by community health workers in cervical cancer screening. AB - BACKGROUND: Cervical cancer remains the leading cause of cancer and mortality in low-resource areas with healthcare personnel shortages. Visual inspection is a low-resource alternative method of cervical cancer screening in areas with limited access to healthcare. OBJECTIVES: To assess accuracy of visual inspection performed by community health workers (CHWs) and licensed providers, and the effect of provider training on visual inspection accuracy. SEARCH STRATEGY: Five databases and four websites were queried for studies published in English up to December 31, 2015. Derivations of "cervical cancer screening" and "visual inspection" were search terms. SELECTION CRITERIA: Visual inspection screening studies with provider definitions, colposcopy reference standards, and accuracy data were included. DATA COLLECTION AND ANALYSIS: A priori variables were extracted by two independent reviewers. Bivariate linear mixed-effects models were used to compare visual inspection accuracy. MAIN RESULTS: Provider type was a significant predictor of visual inspection sensitivity (P=0.048); sensitivity was 15 percentage points higher among CHWs than physicians (P=0.014). Components of provider training were significant predictors of sensitivity and specificity. CONCLUSIONS: Community-based visual inspection programs using adequately trained CHWs could reduce barriers and expand access to screening, thereby decreasing cervical cancer incidence and mortality for women at highest risk and those living in remote areas with limited access to healthcare personnel. PMID- 29788543 TI - New glutathione conjugate of pyrrolizidine alkaloids produced by human cytosolic enzyme-dependent reactions in vitro. AB - RATIONALE: The toxic metabolites of pyrrolizidine alkaloids (PAs) are initially formed by cytochrome P450-mediated oxidation reactions and primarily eliminated as glutathione (GSH) conjugates. Although the reaction between the reactive metabolites and GSH can occur spontaneously, the role of the cytosolic enzymes in the process has not been studied. METHODS: The toxic metabolites of selected PAs (retrorsine, monocrotaline, senecionine, lasiocarpine, heliotrine or senkirkine) were generated by incubating them in 100 mM phosphate buffer (pH 7.4) containing liver microsomes of human, pig, rat or sheep, NADPH and reduced GSH in the absence or presence of human, pig, rat or sheep liver cytosolic fraction. The supernatants were analyzed using liquid chromatography connected to Finnigan LTQ ion-trap, Agilent QTOF or Thermo Scientific Q Exactive Focus quadrupole-orbitrap mass spectrometers. RESULTS: Retrorsine, senecionine and lasiocarpine yielded three GSH conjugates producing [M - H]- ions at m/z 439 (7-GSH-DHP (CHO)), m/z 441 (7-GSH-DHP (OH)) and m/z 730 (7,9-diGSH-DHP) in the presence of human liver cytosolic fraction. 7-GSH-DHP (CHO) was a novel metabolite. Monocrotaline, heliotrine and senkirkine did not produce this novel 7-GSH-DHP (CHO) conjugate. 7 GSH-DHP (CHO) disappeared when incubated with hydroxylamine, and a new oxime derivative was formed. This metabolite was formed only by the human liver cytosolic enzymes but not in the presence of rat or sheep liver cytosolic fractions under otherwise identical reaction conditions. CONCLUSIONS: 7-GSH-DHP (CHO) has not been reported before, and thus it was considered as a novel metabolite of PAs. This may clarify the mechanisms involved in PA detoxification and widely observed but less understood species differences in response to PA exposure. PMID- 29788544 TI - Cochlear implantation using a custom guide catheter in 14 patients with incomplete partition type III. PMID- 29788545 TI - Evaluation of aromatherapy with essential oils of Rosa damascena for the management of premenstrual syndrome. AB - OBJECTIVE: To investigate the efficacy of aromatherapy with essential oils of Rosa damascena for the management of premenstrual syndrome (PMS). METHODS: The present triple-blind randomized clinical trial was conducted between March 5, 2016, and February 20, 2017, among female students attending Shiraz University of Medical Sciences, Shiraz, Iran, who experienced PMS, had a menstrual cycle of 24 35 days, were not using vitamin supplements or hormonal drugs, and did not have any underlying diseases. Block randomization was used to assign participants to an intervention group receiving aromatherapy with R. damascena at a 4% concentration or a control group who received aromatherapy with 100% sweet almond oil. Aromatherapy was performed for 5 minutes, twice daily, for a total of 5 days during the luteal phase. The premenstrual symptoms screening tool questionnaire was completed at baseline and after 1 and 2 months of treatment. Per-protocol analyses were performed with patients and investigators masked to group assignments. RESULTS: There were 66 participants enrolled and 64 completed the study (33 in the intervention group and 31 in the control group). At 2 months, aromatherapy with R. damascena was associated with improved psychological (P<0.001), physical (P<0.001), social (P=0.002), and total (P<0.001) PMS symptoms compared with baseline. By contrast, no improvements were recorded in the control group. CONCLUSION: Aromatherapy with R. damascena improved multiple symptoms of PMS. IRANIAN REGISTRY OF CLINICAL TRIALS: IRCT2016031113940N3. PMID- 29788546 TI - In vitro penetration through the skin layers of topically applied glucocorticoids. AB - Corticoids are actives widely used in the treatment of skin diseases. This work aims to study the penetration of 3 corticoids (betamethasone, clobetasol, and flurandrenolide), their relationship with their Log D values and the effects of the vehicles. The 3 compounds were applied on a Franz-type diffusion cell in propylene glycol solution and their respective commercial creams and ointments. The active amounts found in the stratum corneum, epidermal, and dermal layers of the skin were investigated. Their diffusions were greatly affected by the formulation; moreover higher amounts of substance in the epidermis and dermis were detected in ointments than in creams. The enhancement effect of propylene glycol was also observed. The differences between the 3 substances could be related to their lipophilicity, molecular structure, and molecular weight. The more hydrophobic compounds (clobetasol and betamethasone) are present in higher amounts in the epidermis and dermis, while the hydrophilic compound (flurandrenolide) is mostly present in the receptor fluid. PMID- 29788548 TI - Health perception and adherence with blood pressure control among rural Chinese adults with hypertension. AB - AIM: The aim of this study was to examine associations among blood pressure, personal and illness characteristics, illness perception and medication and self management adherence among adults with hypertension in rural mainland China. BACKGROUND: Despite the high prevalence of hypertension in China, the control rate is only 20%. Identifying factors associated with blood pressure control is critical. DESIGN: Cross-sectional survey. METHODS: Data were collected from 163 hypertensive adults in two rural villages in mainland China. Measures included a demographic questionnaire, the Chinese Illness-Perception Questionnaire-Revised, Medication Adherence Inventory and the Inventory of Adherence to Self-management. Height, weight, and blood pressure were also measured using standard approaches. Hierarchical linear regression was used to assess the association between blood pressure and significant variables identified in bivariate analysis. FINDINGS: The mean systolic pressure observed in this sample was 147 mmHg and the diastolic mean was 81 mmHg. None of the variables analysed were associated with systolic blood pressure. Gender, age, and household annual income were associated with diastolic blood pressure, explaining 23% of the variance in the regression model. Illness coherence contributed an additional 2%. CONCLUSION: These findings suggest: (a) healthcare providers should focus on educating rural hypertensive adults about healthful diets and behaviours to manage hypertension, especially for those with high household income; (b) knowledge-based health education alone is not adequate; (c) illness perception may not be directly associated with blood pressure; and (d) the Chinese Illness-Perception Questionnaire-Revised and the Inventory of Adherence to Self-management require validation and potential revision for use with rural Chinese populations. PMID- 29788547 TI - Premenopausal women with recurrent urinary tract infections have lower quality of life. AB - OBJECTIVES: To examine the impact on quality of life of recurrent acute uncomplicated urinary tract infection among premenopausal Singaporean women, and to determine the risk factors for lower quality of life among these patients. METHODS: A total of 85 patients with recurrent acute uncomplicated urinary tract infection who were referred to the Urology Department at the National University Hospital, Singapore, were prospectively recruited over a 3-year period to complete the validated Short Form 36 Health Survey version 1. In addition, demographic and clinical details including symptomology and medical history were analyzed for factors impacting quality of life. Short Form 36 Health Survey version 1 results were compared with published population norms. RESULTS: After adjusting for age, gender and race, recurrent acute uncomplicated urinary tract infection patients had significantly lower quality of life on seven out of eight Short Form 36 Health Survey version 1 domains when compared with age-, gender- and race-adjusted population norms for Singapore. Among those with recurrent acute uncomplicated urinary tract infection, those who also reported caffeine consumption had significantly lower Short Form 36 Health Survey version 1 scores than those who did not. Those who reported chronic constipation also had consistently lower Short Form 36 Health Survey version 1 scores across all domains. CONCLUSIONS: Recurrent acute uncomplicated urinary tract infection has a negative impact on the quality of life of premenopausal, otherwise healthy women. Recurrent acute uncomplicated urinary tract infection patients who also have chronic constipation or consume caffeine have lower quality of life than those who do not. More studies are required to understand the relationships between these common problems and risk factors. PMID- 29788549 TI - Publication ethic (1) "salami slicing". PMID- 29788551 TI - Defining a land boundary for sustainable livestock consumption. AB - The need for more sustainable production and consumption of animal source food (ASF) is central to the achievement of the sustainable development goals: within this context, wise use of land is a core challenge and concern. A key question in feeding the future world is: how much ASF should we eat? We demonstrate that livestock raised under the circular economy concept could provide a significant, nonnegligible part (9-23 g/per capita) of our daily protein needs (~50-60 g/per capita). This livestock then would not consume human-edible biomass, such as grains, but mainly convert leftovers from arable land and grass resources into valuable food, implying that production of livestock feed is largely decoupled from arable land. The availability of these biomass streams for livestock then determines the boundaries for livestock production and consumption. Under this concept, the competition for land for feed or food would be minimized and compared to no ASF, including some ASF in the human diet could free up about one quarter of global arable land. Our results also demonstrate that restricted growth in consumption of ASF in Africa and Asia would be feasible under these boundary conditions, while reductions in the rest of the world would be necessary to meet land use sustainability criteria. Managing this expansion and contraction of future consumption of ASF is essential for achieving sustainable nutrition security. PMID- 29788550 TI - Ubiquitin-specific protease 22 acts as an oncoprotein to maintain glioma malignancy through deubiquitinating B cell-specific Moloney murine leukemia virus integration site 1 for stabilization. AB - Ubiquitin-specific protease 22 (USP22) is a member of the "death-from-cancer" signature, which plays a key role in cancer progression. Previous evidence has shown that USP22 is overexpressed and correlates with poor prognosis in glioma. The effect and mechanism of USP22 in glioma malignancy, especially cancer stemness, remain elusive. Herein, we find USP22 is more enriched in stem-like tumorspheres than differentiated glioma cells. USP22 knockdown inhibits cancer stemness in glioma cell lines. With a cell-penetrating TAT-tag protein, B cell specific Moloney murine leukemia virus integration site 1 (BMI1), a robust glioma stem-cell marker, is found to mediate the effect of USP22 on glioma stemness. By immunofluorescence, USP22 and BMI1 are found to share similar intranuclear expression in glioma cells. By analysis with immunohistochemistry and bioinformatics, USP22 is found to positively correlate with BMI1 at the post translational level only rather than at the transcriptional level. By immunoprecipitation and in vivo deubiquitination assay, USP22 is found to interact with and deubiquitinate BMI1 for protein stabilization. Microarray analysis shows that USP22 and BMI1 mutually regulate a series of genes involved in glioma stemness such as POSTN, HEY2, PDGFRA and ATF3. In vivo study with nude mice confirms the role of USP22 in promoting glioma tumorigenesis by regulating BMI1. All these findings indicate USP22 as a novel deubiquitinase of BMI1 in glioma. We propose a working model of the USP22-BMI1 axis, which promotes glioma stemness and tumorigenesis through oncogenic activation. Thus, targeting USP22 might be an effective strategy to treat glioma especially in those with elevated BMI1 expression. PMID- 29788553 TI - Enantiomeric resolution of methylamphetamine and ephedrine: Does this affect the delta13 C, delta15 N, and delta2 H stable isotope ratios of the product? AB - The use of stable isotope ratio mass spectrometry (IRMS) as a profiling tool for methylamphetamine has evolved over the last decade. Stable isotope ratios of carbon (delta13 C), nitrogen (delta15 N), and hydrogen (delta2 H) of methylamphetamine are useful in determining the precursor used to manufacture methylamphetamine, and in many cases the synthetic origin of the methylamphetamine precursor. More recently, samples of seized methylamphetamine show that a resolution step is being employed in the manufacturing process. We sought to determine whether the delta13 C, delta15 N, and delta2 H values were affected by either a resolution performed on racemic methylamphetamine or a resolution on racemic ephedrine, a commonly used precursor to methylamphetamine. We found that for the types of resolution studied, IRMS is still able to provide useful information on the provenance of a methylamphetamine sample. PMID- 29788554 TI - Hydrothermal thresholds for seed germination in winter annual forbs from old field Mediterranean landscapes. AB - Under Mediterranean climates with dry-hot summers and cool-wet winters, many forbs with potential for habitat restoration are winter annuals, but there is little information about their germination. We performed laboratory germination experiments on 13 ruderal dicots native to Andalusia (southern Spain). We measured the germination of recently harvested seeds from natural populations across nine temperature treatments (from 5 to 35 degrees C, constant and alternate); two storage periods; and eight water stress treatments (from 0 to 1.0 MPa). We then calculated the hydrothermal thresholds for seed germination. Final germination ranged from 0-100% and results were mixed in response to temperature. Base temperature was below 6 degrees C, optimal temperature was around 14 degrees C and the ceiling temperature around 23 degrees C. For five species, 10 months of storage improved total germination, indicating a dormancy breaking effect, but the other species did not respond or had their germination reduced. All species were relatively tolerant to water stress, with base water potential ranging from -0.8 to -1.8 MPa. Our results suggest that hydrothermal germination thresholds, rather than physiological dormancy, are the main drivers of germination phenology in annual forbs from Mediterranean semi-dry environments. The variation in germination responses of these forb species differs from winter annual grasses, but their seeds are all suitable for being stored before restoration. PMID- 29788555 TI - In Nano, Volume 12, Issue 5. PMID- 29788552 TI - An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy. AB - PURPOSE: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LETd ) is required. In this study, we have developed the analytical LETd calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. METHODS: In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LETd value for the lateral distribution of a pencil beam, the actual LETd increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LETd behavior, we have assumed that the LETs of primary and halo components can take different values (LETp and LEThalo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LETd distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LETd distributions and mean LETd (LETd,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. RESULTS: In the homogeneous phantom, the LETd profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LETd profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LETd,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/MUm in homogeneous phantoms and 0.08 keV/MUm in patient geometries under all tested conditions, respectively. CONCLUSIONS: We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LETd was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs. PMID- 29788557 TI - News & Views in ... Personalized Medicine. PMID- 29788556 TI - Solvent-Mediated End-to-End Assembly of Gold Nanorods. AB - We demonstrate a new method for the bottom-up assembly of anisotropic nanoparticles, showing that alkanethiol molecules can induce controlled end-to end assembly of gold nanorods in mixed water/acetonitrile solutions. The assembly is driven by solvent-mediated interactions among hydrophobic alkanethiol ligands selectively bound to the ends of the nanorods and among hydrophilic cetyltrimethylammonium bromide (CTAB) surfactants on the sides of the rods. It occurs only when the gold-nanorod samples have been aged for approximately two weeks. We compare the kinetics of solvent-mediated assembly using undecanethiol ligands to assembly processes driven by covalent bonding using alpha,omega undecanedithiol ligands and processes driven by hydrogen bonding using 11 mercaptoundecanoic acid ligands. Our experiments demonstrate the different assembly mechanisms involved as well as the conditions needed to obtain selective end-to-end assembly. PMID- 29788559 TI - Letter from the President. PMID- 29788560 TI - Personalized risk stratification for adverse surgical outcomes: innovation at the boundaries of medicine and computation. AB - Patients undergoing surgery exhibit a highly variable risk of mortality and morbidity, even when undergoing similar procedures. Accurately quantifying this risk is critical for preoperative decision-making to ensure patients recieve treatment that is optimal for their individual profile, and for guiding intraoperative and postoperative care. Despite the considerable attention this issue has received, existing models for surgical risk stratification remain grounded in traditional statistical methods and in problem statements that have not evolved significantly over the years. This article explores recent innovations in machine learning and data mining to advance these efforts. Risk stratification models based on sophisticated computational techniques hold the promise of a new generation of predictive analytical tools that are highly accurate and widely deployable. PMID- 29788561 TI - Pharmacogenomics and adverse drug reactions. AB - Adverse drug reactions (ADRs) observed during drug development have been the cause for discontinuing development of many drugs. In addition, serious but rare ADRs observed after marketing have led to withdrawal of some drugs. A priori identification of individuals at risk of developing ADRs for a given drug will help develop strategies to reduce the risk for ADRs in these patients. US FDA initiatives and efforts at reducing ADRs to make drugs safer are described, including updating of drug labels to include genomic information intended to reduce ADRs. Pharmacogenomics can also be harnessed to identify individuals at risk of developing serious ADRs and to treat these individuals with alternative therapy, thus converting ADRs that are traditionally considered unavoidable to avoidable ADRs. PMID- 29788562 TI - Behavioral phenotyping: a tool for personalized medicine. AB - In recent years, genetic mapping has been grabbing the headlines for its promise to revolutionize healthcare and provide us with a way to personalize medicine. Connected health uses objective data and automated feedback to monitor chronic illnesses and has demonstrated exciting possibilities too. This data can create phenotype maps that reveal acquired behaviors and individual responses to health programs. Health interventions can be personalized using a combination of these techniques to maximize the chances of success and minimize adverse reactions. Aggregating this data at a population level can help us leverage collective behavioral trends to alter health-related perceptions at a population level. This method of hyperpersonalization of medicine has proven its worth, and the focus should now shift to testing its feasibility and incorporation into clinical workflow. PMID- 29788564 TI - Collaboration as a foundation for advancing research in personalized medicine in cancer care. AB - Transforming healthcare through collaborative relationships is the key to making successful advances in personalized medicine. The strategies for building a framework to bring together expertise and resources in order to realize all the possibilities of personalized medicine are discussed in this article. The key to this endeavor is the ability to identify potential collaboration with academic medical centers, research laboratories, biotechnology companies and community cancer centers. Translation of research from bench to bedside is only paradigm changing if it can then be translated to community care. The value of clinical prospective biospecimen collection with high quality clinical annotation will be explored. Recognizing the opportunities for performing clinical trials, beta testing of new technology especially in community clinical practice will be emphasized. The goal is to expand the realm of personalized cancer care to allow for integration of molecular marker and individualized therapy to the majority of cancer patients worldwide. PMID- 29788566 TI - Telomere length maintenance: a factor to be considered in personalized medicine? PMID- 29788565 TI - Breath biomarkers for personalized medicine. AB - Personalized medicine, in the near future, has the potential to revolutionize healthcare by allowing physicians to individualize therapy for patients through the early diagnosis of disease and risk assessment to optimize clinical response with minimal toxicity. The identification of biomarkers could detect, diagnose and help guide therapy to improve survival and quality of life by the early identification of responders to the drugs. Volatile organic compounds and stable isotope-labeled 13CO2 in breath can be uniquely utilized as in vivo diagnostic biomarkers of disease and/or lack of enzyme activity to aid physicians to personalize medication. Noninvasive detection of ailments and monitoring therapy by human breath analysis is an emerging field of medical diagnostics representing a rapid, economic and simple alternative to standard invasive blood analysis, endoscopy or harmful imaging techniques such as x-ray and CT scans. PMID- 29788567 TI - U-Health: an example of a high-quality individualized healthcare service. AB - National Taiwan University Hospital (Taipei, Taiwan), which is one of the largest hospitals in Taiwan, is undergoing healthcare service reforms: it is combining the home healthcare service network and sensors network into a new service known as the Ubiquitous Healthcare (U-Health) service system in order to continually provide a personalized healthcare service to patients who live in remote areas. The U-Health service system is comprised of six service components that are introduced in an integrated manner: tele-education, telediagnosis, telemonitoring, teleconsultation, teletherapy and lifetime health. The target patient segments are postdischarge patients, patients suffering from cardiovascular diseases, patients suffering from chronic diseases and patients in hospice care. Since its launch in October 2009, the U-Health service system has effectively reduced the rehospitalization rate from 12% in October 2009 to 6% in May 2010 and the rate of visiting the emergency room from 21% in October 2009 to 9% in May 2010, during the 14-day postdischarge follow-up period. PMID- 29788568 TI - Genetics of osteoporosis: perspectives for personalized medicine. AB - Osteoporosis is the most common metabolic bone disorder worldwide. At least 15 genes (e.g., ESR1, LRP5, SOST, OPG, RANK and RANKL) have been confirmed as osteoporosis susceptibility genes, and another 30 have been highlighted as promising susceptibility genes. Notably, these genes are clustered in three biological pathways: the estrogen endocrine pathway, the Wnt/beta-catenin signaling pathway and the RANK/RANKL/osteoprotegerin (OPG) pathway. In this article, using data pertaining to these three biological pathways as examples, we illustrate possible principles of personalized therapy for osteoporosis. In particular, we propose to use inhibitors (e.g., denosumab) of the RANK/RANKL/OPG signaling pathway to circumvent resistance to estrogen-replacement therapy: a novel idea resulting from the consideration of a mechanistic link between the estrogen endocrine pathway and the RANK/RANKL/OPG signaling pathway. In addition, we call for more attention to be focused on rare variants of major effects in future studies. PMID- 29788569 TI - Personalized medicine conference. PMID- 29788570 TI - HER2 status is an important biomarker in guiding personalized HER2 therapy. AB - The human epidermal growth factor receptor (HER)2 oncoprotein has emerged as an important cellular target for the development of a variety of new cancer therapies. The method used to define the HER2 status is a major factor in determining who will receive these targeted therapies. The HER2 status can be determined by using either tissue tests to look at the primary tumor cells, or an enzyme-linked immunosorbent assay (ELISA) that measures the circulating levels of the extracellular portion of HER2 protein. Tissue test (immunohistochemistry and fluorescence in situ hybridization) results indicate that approximately 20-30% of patients with primary breast cancer have a HER2-positive tumor, whereas ELISA results demonstrate that an average of 45% (range: 23-80%) of metastatic breast cancer (MBC) patients can have an abnormally high (> 15 ng/ml) serum HER2 level, which is evidence that a HER2-positive tumor is present. Published studies show that the HER2 status of a breast cancer patient can differ both by the test method used and the time at which HER2 status is assessed. In this review, data will be shown that demonstrates that not all HER2 test results obtained from the primary breast cancer are correct, and that there is a population of patients categorized as HER2 negative by tissue tests that, in fact, have HER2-positive tumors. This observation has important therapeutic implications for breast cancer patients with HER2-positive tumors that are classified as HER2 negative, since they are not eligible for anti-HER2 therapy, such as trastuzumab. If a patient is found to have an elevated (> 15 ng/ml) serum HER2 level in MBC, then either the original tumor should be re-evaluated for HER2 status, or a metastatic lesion should be tested for HER2 positivity, to determine if the patient is eligible for anti-HER2 therapy. Studies have also shown that lack of adequate validation of a testing method can result in false conclusions concerning the HER2 status. If the goal of personalized medicine is to deliver the right treatment to the right patient at the right time then we need to ensure the validity of all test methods, regardless of whether they are for research purposes or are registered as in vitro diagnostics. In the case of establishing HER2 status, it takes more than one type of test to identify patients with HER2-positive tumors. It is highly likely that the introduction of additional targeted drugs to growth factor receptors or to angiogenesis targets will take a variety and combinations of tests to tailor the most appropriate therapy to the patient. PMID- 29788572 TI - Monogram Biosciences, Inc. AB - Monogram Biosciences, Inc., formerly ViroLogic, Inc., develops and commercializes diagnostic tests to help guide and improve the treatment of infectious diseases, cancer and other serious illnesses. The company's base business is HIV patient and pharmaceutical testing, where individualized medicine has been in practice for many years and is now an established reality. The recent name change reflects the company's broader commitment to extend its pioneering efforts in individualized medicine beyond viral diseases and into oncology and other serious diseases. Monogram's products are designed to help doctors optimize treatment regimens for their patients, which leads to better outcomes and reduced costs. Its technology is also being used by numerous biopharmaceutical companies to develop new and improved antiviral therapeutics and vaccines, in addition to targeted cancer therapeutics. PMID- 29788573 TI - DNA methylation markers - an opportunity to further individualize therapy in breast cancer? AB - Over the last few decades, a wealth of treatment options have become available for breast cancer. To specifically direct those therapies to patients with the highest need who will receive the greatest benefit, biomarkers are urgently needed. Two specific needs seem to be most pressing: first is the need for prognostic markers, which would determine which group of patients may recover without adjuvant chemotherapy. Second, predictive markers for specific treatments, such as different endocrine treatments, chemotherapies or targeted drugs, are expected to play a major role in the near future. Ideally, such markers should be strong single markers, or low-complexity marker panels containing only a few markers, to allow for easier assay development and improved reproducibility. The possibility to measure the marker(s) in formalin-fixed specimens would greatly facilitate integration into routine clinical practice. A common and early event in breast cancer is aberrant DNA methylation within gene regulatory regions, affecting a variety of genes with different functions. Data from recently published studies indicate that altered DNA methylation carries prognostic as well as predictive information in breast cancer. Together with the technical advantages of a DNA-based marker, DNA methylation may well constitute the ideal biomarker to further individualize breast cancer treatment. Here the recent literature is reviewed and the most interesting markers, which have the potential to significantly change breast cancer treatment and, therefore, warrant further systematic clinical validation, are highlighted. PMID- 29788574 TI - Use of pharmacogenetics in clinical medicine: hype or hope? PMID- 29788575 TI - Quantitative in situ cancer proteomics: molecular pathology comes of age with automated tissue microarray analysis. AB - Tissue microarrays provide a high-throughput method for assessing a large number of samples by incorporating small cores of tissue into an array that can fit onto one microscope slide. Analyses of tissue microarrays were previously limited by semiquantitative protein expression analysis using brown stain (chromagen-based) methods. These methods are imperfect for protein expression analyses because of a smaller dynamic range and decreased ability for multiplexing many markers, as compared with objective in situ quantitation of protein expression in tumor samples with fluorescence microscopy by a new technology called Automated Quantitative Analysis (AQUATM). By using AQUA analysis, tissue microarrays can serve a unique role as both a discovery tool and as a validation tool for nucleic acid expression profiling-based target discoveries with results equivalent to enzyme-linked immunosorbent assay quantitation. The identification of novel prognostic markers can identify subsets of patients at high or low risk upon diagnosis, as well as new targets for potential future therapeutic development or metastatic disease treatment decisions. Thus, AQUA provides an unparalleled opportunity to advance personalized medicine through its ability to multiplex, quantitate and localize in situ protein expression. PMID- 29788576 TI - Individualized therapy for childhood acute lymphoblastic leukemia. AB - In the field of oncology, a growing emphasis is now being placed on individualizing treatment in a way that maximizes chance for cure while minimizing unwanted side effects. In childhood acute lymphoblastic leukemia (ALL), several well-established clinical and biologic prognostic variables have traditionally been used to risk stratify therapy for individual patients. While this approach has been very successful, many relapses still occur unpredictably in patients characterized as having favorable features of their disease at diagnosis. Furthermore, it is likely that other children are overtreated. Therefore, current initiatives in childhood leukemia have focused on identifying new prognostic markers to refine treatment decision-making. Recent advances, which include the sequencing of the human genome, and technical developments in high-throughput genomics and proteomics, have facilitated these efforts. This review will chart the evolution of individualized therapy for ALL, the most common malignancy of children. PMID- 29788577 TI - Program for the Assessment of Clinical Cancer Tests (PACCT): assisting the development of tailored cancer therapy. AB - Fulfillment of the promise of the genomic revolution for personalizing cancer therapy will depend on the ability to identify specific alterations in tumor cells that are critical to their growth, and the development of drugs that can target these alterations and inhibit their growth. In this report, examples of where this has been successful are discussed, and the challenges faced in other cases are described. The identification of the patients most likely to benefit from targeted agents requires significant investment in the development and validation of predictive assays. The Program for the Assessment of Clinical Cancer Tests (PACCT) has proposed an approach that should speed the development of the diagnostic tools required and their acceptance into clinical practice. This approach is dependent on determining the most pressing clinical questions confronting clinicians today and the availability of adequate specimens to validate the assays. PMID- 29788578 TI - Pharmacogenomics steps toward personalized medicine. AB - The goal of personalized medicine is to maximize the likelihood of therapeutic efficacy and to minimize the risk of drug toxicity for an individual patient. One of the major contributors to this concept is pharmacogenomics. Marked interindividual genetic variation contributes significantly to both susceptibility to diseases, and response to drugs. Even though pharmacogenomics is not a new science, the translation of pharmacogenomics into clinical practice (i.e., personalized medicine) has not taken place at the same pace as science is delivering new results. It is felt that a large number of recent pharmacogenomic findings allow bold steps to be taken toward personalized medicine. This review collates a variety of examples that have great potential for immediate and effective introduction into clinical practice. In addition, other exploratory examples with a particular focus on drug safety and targeted cancer therapy are summarized. PMID- 29788579 TI - The era of ErbB-receptor-targeted therapies: advances toward personalized medicine. AB - Central themes in medical practice are the diagnosis, prognosis and treatment of disease. Advances have been made in a number of malignanices including breast cancer, where new therapeutic strategies have significantly improved response rates, the disease-free interval and overall survival. However, complete responses to chemotherapy are achieved in only 10-20% of patients. Recent advances in the understanding of the cellular and molecular biology of cancer have led to the identification of oncogenes and tumor suppressor genes that influence the rate of tumor cell proliferation and cancer progression. These oncogenes represent important therapeutic targets and are currently being incorporated into the design of novel therapeutic approaches. This review emphasizes the role of the ErbB oncogenic receptor family, its effect on tumor biologic behavior and its role as a target for various therapeutic regimens. PMID- 29788580 TI - New indication for Herceptin in early stage breast cancer. PMID- 29788581 TI - Workshop: Personalized Medicine Europe: Health, Genes and Society. PMID- 29788582 TI - DxS Ltd. AB - DxS is a personalized medicine company focused on providing genetic analysis services and technologies to enable the delivery of safe and effective medicines. The services provide support for drug development, diagnostic product development and pharmacodiagnostics. There is an increasing demand from the pharmaceutical industry for genetic analysis of clinical trial populations to help to understand individual variation in drug pharmacokinetics and pharmacodynamics. Since these studies are part of a clinical trial it is essential that they are performed in a high quality environment that meets relevant regulatory standards. DxS operates a genotyping service operation that fulfils all of these requirements. One of the expectations deriving from the growing use of pharmacogenetics during clinical development is that some of the genetic markers will be required as diagnostics to allow the identification of suitable patients for a therapy. This combination of a drug and a diagnostic is called personalized medicine. DxS have established a global network of alliance laboratories to allow the rapid translation of tests from clinical development into clinical diagnostics. PMID- 29788583 TI - Workshop Introduction: Personalized medicine: desirable, affordable, attainable? AB - The Human Genome Project, the most celebrated human consortium effort in biomedicine and one of the greatest scientific achievements of modern time, has yet to deliver the anticipated improvements in healthcare [1] . The blueprint of a human being, the complete 3.2 billion nucleotides of the human DNA sequence, has been available since April 2002. Up to the present day, however, we still understand very little about the biology of common complex disorders, such as diabetes, hypertension, osteoarthritis, osteoporosis, Alzheimer's disease, schizophrenia, and depression, despite the fact that the genetic determination of each of these conditions is reliably established. PMID- 29788584 TI - Single nucleotide polymorphisms: discovery, detection and analysis. AB - Single nucleotide polymorphisms (SNPs) are the most abundant and simple form of DNA variation. Analyses of SNPs in the human population have the potential to greatly improve human health, both by predicting susceptibility to disease and guiding choice of therapy. This review describes new tools for SNP discovery, and current and emerging technologies for large-scale SNP analysis, as well as providing a guide to choosing the best approach for SNP analysis. PMID- 29788585 TI - Clinical implementation of psychiatric pharmacogenomic testing. AB - For the past 5 years, many investigators have suggested that psychiatrists are on the verge of using genotyping to guide clinical psycho-pharmacological practice. After much anticipation, the first applications of this new technology are being used to select psychotropic medication and inform individual variation in the appropriate dose of medication. Not surprisingly, the drug-metabolizing enzyme genes have been the first genes to be clinically genotyped for psychiatric practice. PMID- 29788586 TI - Personalized diagnostic and therapeutic strategies in oncology. AB - In our lifetimes we hope to see the genome transform diagnosis and facilitate individualized management of cancer. In the foreseeable future, cancer genomes and transcriptomes will be identified and cataloged, and pathway-specific therapies will continue to be developed. Population-wide databases will be used to assist physicians in guiding patients to the appropriate therapy for their tumor. Already there are early outstanding examples of the successful application of genetic and genomic data to guide cancer therapy. However, truly tailored therapeutics in oncology will require genomic analyses of an individual's tumor as well as a more comprehensive assessment of their genetic background, health, and environment exposures in order to determine the risk of disease, the dose requirements for drugs, and the likelihood of response. Tumor genomics will eventually result in a comprehensive description of cellular processes critical to cancer growth for subsequent therapeutic impact. While there will be significant technical and societal challenges to overcome, the integration of personalized medicine into clinical practice is anticipated by clinicians, expected by patients, and represents the likely future of oncology. PMID- 29788587 TI - Innogenetics NV. AB - Innogenetics NV is a Belgium-based international biopharmaceutical company that has applied its know-how and synergies in molecular biology, immunology and virology to build two distinct businesses: a specialty diagnostics business grounded in personalized medicine, and a pharmaceutical business that is developing therapeutic vaccines. The advantage of this dual model is that the growing revenues from the profitable specialty diagnostics business partially support the development of its biopharmaceutical pipeline. The company employs some 600 persons, with affiliates in Germany, Spain, Italy, France, and the USA. PMID- 29788588 TI - Workshop Abstracts. AB - The first and crucial step in sensory processing, the transduction of stimuli, such as odor, light and sound, into a cellular response, are all regulated by genetic pathways. The past years have provided a significant increase in our understanding of some of these pathways, due in large part to the genes found to be associated with inherited hearing loss (HL). PMID- 29788589 TI - Initial development of an evidence base for personalized medicine's translation to clinical practice and health policy. AB - A major challenge to adoption of personalized medicine approaches, such as pharmacogenomics, is that data to address many critical questions relevant to clinical application, economics, policy and regulation are typically unavailable or widely dispersed. The evidence base we tentatively call Evaluation Data for Assessing Personalized Medicine Translation (EDAPT) would generate the foundation for a database of information. This article begins with a description of the rationale and conceptual framework for this effort. PMID- 29788590 TI - Leading the way to personalized pain therapy. PMID- 29788591 TI - Genetic association studies: where are we now? PMID- 29788592 TI - Legal pressures and incentives for personalized medicine. AB - Legal liability has the potential to be a powerful driver pushing implementation of personalized medicine. Individuals injured by adverse drug effects are increasingly likely to bring lawsuits alleging that they have a polymorphism or biomarker conferring susceptibility to the drug that should have been identified and used to alter their drug treatment. Likely targets of such lawsuits include drug manufacturers, third party payors, physicians and pharmacists, of which physicians are most at risk of substantial liability. PMID- 29788593 TI - Translational pharmacogenetics and risk management in the cardiovascular arena: CYP3A5*3 model for gene-based drug selection. AB - The clinical community is moving rapidly toward the prospective application of gene-based drug dosing. Specifically within the cardiovascular arena, the cytochrome P450 (CYP)3A5*3 allele may represent an optimal starting point. All CYP3A5*3 alleles contain an A6986G transition in intron 3, which reduces enzyme expression through the introduction of a premature stop codon. The current review explores four potential reasons why the clinical and scientific communities should consider including CYP3A5*3 in any panel of gene polymorphisms developed for the purpose of guiding cardiovascular pharmacotherapy: the CYP3A enzyme family metabolizes nearly half of all prescription drugs; the CYP3A enzyme family metabolizes several drugs utilized for primary and secondary risk reduction in the context of coronary artery disease; the CYP3A5*3 allele has been associated with differential outcomes related to lipid lowering therapy; and the CYP3A5*3 allele is highly prevalent in all populations studied to date. PMID- 29788594 TI - Personalized medicine for breast cancer: moving forward and going back. PMID- 29788595 TI - Novel personalized medicine technology: UGT1A1 testing for irinotecan as a case study. AB - Third Wave's Invader(r) UDP glucuronosyltransferase 1A1 (UGT1A1) Molecular Assay, a genotyping system to predict adverse drug reactions in patients receiving the chemotherapeutic agent irinotecan (Camptosar(r), Pzifer, NY, USA) for the treatment of metastatic colorectal cancer (mCRC), was recently approved by the US FDA. Clinical application, economic and regulatory data were collected on this test in the Evaluation Data for Assessing Personalized Medicine Translation (EDAPT) evidence base. This descriptive analysis highlight these data and the issues for the translation of this test to practice, including gaps in the evidence base, issues regarding adoption of the test to clinical practice and the potential societal impact of UGT1A1 testing for irinotecan prescribing. PMID- 29788596 TI - Innovation in personalized medicine: BiDil(r) as a case study for integrating clinical and policy developments. AB - BiDil(r) (hydralazine and isosorbide dinitrate) represents an interesting application of personalized medicine - the first pharmaceutical specifically approved by a regulatory agency, the US FDA, for an indication in a particular population based on race as a surrogate phenotypic marker, without a companion genomic diagnostic directed at measuring drug responsiveness. The focus of this paper is to use BiDil as a case study of a personalized medicine application and evaluate its clinical and policy-relevant characteristics as an illustrative example of the usefulness of the Evaluation Data for Assessing Personalized Medicine Translation (EDAPT) evidence base. PMID- 29788597 TI - Epigenomics AG. AB - Earlier diagnosis and a more individualized choice of treatment options has the potential to greatly improve the outcome of life-threatening diseases. DNA methylation has proven to be a rich source of biomarkers for diagnosis, prognosis and drug response prediction in cancer and other diseases. Epigenomics AG makes use of DNA methylation biomarkers to develop in vitro diagnostic test products. The product pipeline comprises screening tests for the early detection of cancer in body fluids and molecular pathology tests on routinely available tissue samples for cancer prognosis. In collaborations with pharmaceutical and biotechnology companies, Epigenomics provides access to its broad range of technologies for the support of drug development and commercialization by patient stratification and drug response prediction. PMID- 29788599 TI - Letter from the Executive Director. PMID- 29788598 TI - Role of the Opportunity To Test Index in integrating diagnostics with therapeutics. AB - In theory, the introduction of a novel test to accompany a therapy should be simple and automatic. However, In reality, the marriage of a test with therapy will not be a simple one, since each industry operates with its own distinct business model. Of concern to the pharmaceutical industry is the potential commercial dependency of a drug on the performance and implementation of a diagnostic. These concerns are justified since the history of diagnostic tests is frequently one of under use. One of the factors cited by Rogers is the issue of how complex an innovation is to administer. Rogers demonstrates that an innovation that is difficult to administer will be implemented more slowly or be discontinued by the user group it was intended for. It is the author's view that understanding this micro interaction, experience and barriers of testing with the individual provider, in short the complexity of the test, will, in turn, provide those in the pharmaceutical industry with a methodology to consider their risk or exposure to a test upon which their therapy may become dependent in the US market. Since personalized medicine significantly marries the test and treatment decision, it is the perspective of the provider that will be paramount in determining which, if any, test is ordered and the subsequent clinical decision he or she is enabled to take upon the test response. Therefore, a focus of this perspective is to consider the issues of test implementation from the perspective of the US provider who will order and use the information they provide. The Opportunity To Test Index methodology is introduced, which the authors speculate may help quantify the level of risk a pharmaceutical company has to the complexity of a test upon which its therapy will be dependent. The methodology scores five key elements impacting test implementation: reimbursement, turnaround time, test administration, test interpretation and patient engagement. PMID- 29788600 TI - Identification of gene signatures involved in the mechanisms of multidrug resistance. PMID- 29788601 TI - Genomics and personalized medicine: a perspective. AB - Dr Desnick is Professor and Chairman of the Department of Genetics and Genomic Sciences and Associate Dean for Genome-Based Research at The Mount Sinai School of Medicine (NY, USA) and Physician-in-Chief of the Department of Medical Genetics and Genomics at the Mount Sinai Hospital (NY, USA). In 1977 he joined the faculty of The Mount Sinai School of Medicine as the Arthur J and Nellie Z Cohen Professor of Pediatrics and Genetics, and as Chief of the Division of Medical and Molecular Genetics. In 1993 he became the first Chairman of the Department of Genetics and Genomic Sciences at The Mount Sinai School of Medicine. Dr Desnick's research interests include molecular and biochemical genetics. He has published over 600 research papers and chapters, including nine edited books. He is Board Certified in clinical, biochemical and molecular genetics by the American Board of Medical Genetics (MD, USA) and is a Fellow of the American Academy of Pediatrics (IL, USA). He has been the recipient of various fellowships and awards and is a past Chair of the American Association of Medical Colleges (DC, USA), a Fellow of the American Academy for the Advancement of Science (DC, USA) and a member of the Institute of Medicine of the National Academy of Sciences (DC, USA). PMID- 29788602 TI - Personalized Health Care National Conference: translating science into personalized healthcare. PMID- 29788603 TI - A new series of international genetic congresses take place in China. PMID- 29788604 TI - News & Views in Personalized Medicine. PMID- 29788606 TI - Recent advances in personalizing rheumatoid arthritis therapy and management. AB - Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterized by synovial inflammation in diarthrodial joints. There are significant interindividual variations in the degree of inflammation, disease course and the rate of joint progression in patients with RA. A number of clinical, serological, environmental and genetic severity factors have been identified in patients with RA and can be used to help guide treatment. Therapeutic options for RA have significantly expanded in the last decade and now include both synthetic disease-modifying antirheumatic drugs as well as biologic disease-modifying antirheumatic drugs. Owing to the variety of new drugs, their cost and incomplete information on side effects, markers of treatment response are needed. The study of treatment-specific genetic and protein biomarkers of response and toxicity in RA has produced exciting, yet inconsistent, results. Large scale genetic and proteome studies, which can now be performed at a relatively low cost, will likely broaden the scope and significance of biomarker studies in RA. Integration of these results into clinical practice will vastly improve our ability to provide safe and effective therapy to individuals with RA. PMID- 29788607 TI - Vilazodone, a novel, dual-acting antidepressant: current status, future promise and potential for individualized treatment of depression. AB - Vilazodone is a novel antidepressant with a dual mechanism of action that combines selective serotonin reuptake inhibition and partial 5 hydroxytryptamine1A receptor agonism. Vilazodone is undergoing clinical development for the treatment of major depressive disorder and has demonstrated antidepressant efficacy. In addition, in a placebo-controlled, randomized study, vilazodone has been shown to be well tolerated with a low discontinuation rate due to adverse events. Importantly, in this study, the incidence of sexual dysfunction with vilazodone was similar to that of the placebo. A key feature of the vilazodone clinical development program is the identification and development of biomarkers that predict response to therapy. This article will review the pharmacology, efficacy and tolerability, and pharmacogenetic data of vilazodone for the treatment of major depressive disorder. Vilazodone may be the first antidepressant to provide targeted therapy to patients most likely to achieve a response, and to offer an individualized approach to therapy. PMID- 29788608 TI - What do leaders of disease-specific advocacy organizations know about pharmacogenomics and biomarkers, anyway? AB - Disease Advocacy Organizations (DAOs) make meaningful contributions to the development of tests and therapeutics across the development pipeline, from cohort development to actual drug discovery. The process of developing biomarkers and validating them is fraught with a high failure rate and enormous expense. DAOs can harness new information technologies to increase effectiveness, including systems to dynamically consent individuals to participate in registries and trials. These new technologies can alleviate some of the expense in biomarker development. Information aggregation with consumer control of information at its core will eventually permit a national surveillance system for pre- and post treatment analysis. A stronger and more scientific basis on which to build quality control and assurance of biomarker determination is needed. Validation must be supported in the future, in the same manner discovery was in the past, including through federal funding and philanthropic giving. DAOs can accelerate the process of biomarker development by building robust, well-characterized cohorts. PMID- 29788609 TI - Clinical pharmacy consultation for pharmacogenetic testing. AB - The clinical application of pharmacogenetic testing will help to bring personalized medicine into clinical practice. Due to the complex process involved in delivering pharmacogenetic testing, optimal clinical implementation of pharmacogenetic tests will require the coordinated effort of multiple disciplines including medicine, clinical laboratory medicine and clinical pharmacy. This will help to bridge the gap between the basic and laboratory science, and the clinical application of these results. How may clinical pharmacy contribute to the clinical application of pharmacogenetic testing as a member of a multidisciplinary team? In this perspective, we propose a potential new role for pharmacists: as an interpreter of pharmacogenetic test results. Interpreting the results of pharmacogenetic tests, particularly, those intended to guide drug dosing, requires an understanding of pharmacogenetics, pharmacokinetics and pharmacodynamics. Pharmacists who are knowledgeable in these areas may play an important role in interpretation of the test results. PMID- 29788610 TI - Toward an individualizing therapy for colorectal cancer: the example of the anti EGFR monoclonal antibodies. AB - Anti-EGF receptor (EGFR) antibodies (cetuximab and panitumumab) have been demonstrated to be efficient in the treatment of metastatic colorectal cancer. However, these costly and potentially toxic treatments are active in a subset of patients, which renders necessary the identification of factors that are able to better define which patients will benefit from these treatments. Advances in the understanding of signaling pathways inhibited by these targeted therapies led to the identification of KRAS mutations as a strong predictor of resistance to anti EGFR therapies. Other molecular markers, which are involved in the EGF signaling pathway or in the antibody dependent cell-mediated cytotoxicity-related anti tumor effect of these anti-EGFR therapies, are also interesting and will have to be evaluated in future clinical trials. PMID- 29788612 TI - Personalizing medicine through targeted agents, capitalizing on pathway dysregulation and biomarker use. PMID- 29788613 TI - Individualized therapy of breast cancer: are we there yet? PMID- 29788614 TI - The biomarker revolution: a step toward personalized medicine. PMID- 29788615 TI - Interview. AB - Charis Eng is the Chairman and founding Director of the Genomic Medicine Institute of the Cleveland Clinic Foundation, founding Director and attending clinical cancer geneticist of the institute's clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics at Case Western Reserve University School of Medicine. She holds a joint appointment as Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and is a full member of Cleveland Clinic's Taussig Cancer Center and of the CASE Comprehensive Cancer Center. Dr Eng was recently honored with the Sondra J and Stephen P Hardis Endowed Chair in Cancer Genomic Medicine. She continues to hold an honorary appointment at the University of Cambridge. Dr Eng's research interests may be broadly characterized as clinical cancer genetics translational research. Her work on RET testing in multiple endocrine neoplasia type 2 and the characterization of the widening clinical spectra of PTEN gene mutations have been acknowledged as the paradigm for the practice of clinical cancer genetics. PMID- 29788616 TI - News & Views. PMID- 29788617 TI - Latest News & Updates from the Personalized Medicine Coalition. PMID- 29788619 TI - Increased carrier prevalence of deficient CYP2C9, CYP2C19 and CYP2D6 alleles in depressed patients referred to a tertiary psychiatric hospital. AB - OBJECTIVE: This study compared the types and carrier prevalences of clinically significant DNA polymorphisms in the cytochrome P450 (CYP450) genes CYP2C9, CYP2C19 and CYP2D6 in major depressive disorder patients with a control group of nonpsychiatrically ill, medical outpatients. METHOD: We conducted a case-control study using 73 psychiatric outpatients diagnosed with depression and referred to a tertiary center, The Institute of Living (Hartford, CT, USA), for treatment resistance or intolerable side-effects to psychotropic drugs. The controls were 120 cardiovascular patients from Hartford Hospital being treated for dyslipidemia but otherwise healthy and not psychiatrically ill. DNA typing to detect polymorphisms in the genes CYP2C9, CYP2C19 and CYP2D6 was accomplished with the Tag-ItTM mutation detection assay and the Luminex xMAP(r) system. RESULTS: The percentage of individuals in psychiatric versus control groups with two wild-type alleles for CYP2C9, CYP2C19 and CYP2D6 genes, were 50 versus 74% (p < 0.001), 71 versus 73% (not statistically significant) and 36 versus 43% (trend, p < 0.2), respectively. Within the psychiatric population, 57% of individuals were carriers of non-wild-type alleles for 2-3 genes, compared with 36% in the control population (p < 0.0001). The balance, 43% in the psychiatric population and 64% in the control, were carriers of non-wild-type alleles for none or one gene. CONCLUSIONS: These findings reveal that clinically relevant CYP2C9 polymorphisms occur more frequently in depressed psychiatric patients than in nonpsychiatric controls. The same trend was found for polymorphisms in the CYP2D6 gene. We found a significant cumulative metabolic deficiency in the psychiatric population for combinations of the CYP2C9, CYP2C19 and CYP2D6 genes. The significant enrichment of CYP2C9-deficient alleles in the psychiatric population validates a previously reported association of this gene with the risk for depression disorders. The high prevalence of carriers with deficient and null alleles suggests that CYP450 DNA typing may play a role in the management of psychiatric patients at tertiary care institutions. PMID- 29788620 TI - Considerations for a business model for the effective integration of novel biomarkers into drug development. AB - It is 10 years since the introduction of trastuzumab into the US market, and we are still waiting for a validation of the business case for biomarker-driven drug development. While many reasons for the lack of duplication of this model may exist, the need for accelerated innovation in drug development paired with the opportunity of integrating biomarker-driven research into drug development programs may lead to new and creative ways of fostering the cooperation between drug developers and test manufacturers. The rapid increase in knowledge about biomarkers and our understanding of disease and disease mechanisms open unprecedented prospects to make not only better, more informed decisions regarding patient care, but also strategic decisions during drug development. This requires that a biomarker strategy becomes an integral part of (early) drug development and that new, innovative paths are tried towards a model that combines the scientific approach with an economically feasible implementation strategy. Collaborative research, the use of new communication tools, the exploration of alternative ways to position a product in the market, and other considerations are part of such a strategy. This perspective article illustrates the current landscape and takes a look at some of these new ways for more effectively integrating biomarkers into drug development. PMID- 29788621 TI - Molecular pathogenesis of inflammatory bowel disease: relevance for novel therapies. AB - The immense load of microorganisms within the gastrointestinal tract is a great challenge for the mucosal immune system. Whereas the vast majority of commensal bacteria should be tolerated, pathogenic organisms have to be attacked. During inflammatory bowel disease, the balanced interaction between the mucosal flora and the intestinal immune system is disturbed. Various defective components of this complex interaction have been described, such as different susceptibility genes, impaired innate immune responses and environmental factors, suggesting that inflammatory bowel diseases are multifactorial diseases. Based on new insights into the pathogenesis of inflammatory bowel disease, various targets for future drugs have been identified and new substances are emerging. The following article will review the current understanding of inflammatory bowel disease pathogenesis in context with genetic risk factors, imbalanced innate and acquired immune responses, and altered barrier function. Clinical treatment of the diseases will be summarized and emerging therapies as well as individual management based on recent insights into pathogenesis will be discussed. PMID- 29788623 TI - Personalized medicine: a perspective on the patient, disease and causal diagnostics. PMID- 29788622 TI - Pharmacogenetic tools for malaria and TB in the Developing World. AB - Some of the largest therapeutic drug exposures in the planet involve drugs employed against malaria and TB, two main global infectious diseases. Amodiaquine for malaria and isoniazid for TB are two pivotal drugs in the management of these diseases. Both drugs have been associated with severe adverse events. Amodiaquine and isoniazid are metabolized polymorphically by CYP2C8 and N-acetyltransferase 2, respectively. The polymorphic genes coding for these enzymes presently represent the best candidates for the application of personal pharmacogenetics for these diseases. We review the main reasons for this view, while asking the pivotal question of whether it is presently possible for pharmacogenetic-based personalized medicine to be applied in the malaria and TB settings of the Developing World. PMID- 29788624 TI - The right prescription for personalized genetic medicine. PMID- 29788625 TI - Low adoption of pharmacogenetic testing: an exploration and explanation of the reasons in Australia. AB - The research reported here sought to identify and illuminate the reasons for the low adoption of pharmacogenetic tests in Australia. The research initially established possible reasons and propositions drawn from previous studies and surveys on the problem in Europe and the literature on the adoption of innovations. A small-scale exploratory, qualitative study was undertaken in one state in Australia; clinicians and other stake-holders were interviewed about their use of or support for pharmacogenetic tests. The expected, quite extensive individual factors known to influence adoption and rejection of innovations were found to be present in the situations covered. The reasons for nonadoption that were found in previous surveys were also supported. Some other, possibly critical, reasons were also identified. The implications from this initial exploration are discussed and the prospects for the increased use of the tests proposed. PMID- 29788626 TI - Use of miRNA expression profiling to identify novel biomarkers. AB - Micro (mi)RNAs are small, noncoding RNAs that regulate gene expression through binding to the 3'-untranslated region of mRNAs by complementary base pairing and mainly act through cleavage or translational inhibition of mRNAs. Recent studies have shown the roles of miRNAs in development and cancer, revealing the physiological and pathological importance of these tiny molecules. Therefore, as with mRNAs, researchers have focused on the global analyses of miRNAs to seek their potential use as biomarkers for physiological and pathological states of a cell. Methods developed for miRNA profiling are briefly discussed in this review. Recent evidences supporting the use of miRNAs as biomarkers in both differentiation and cancer are presented. The profiling studies may highlight the clinical relevance of miRNAs and will enable the researchers to uncover the enormous potential of these tiny molecules. In the near future, selected miRNA genes based on expression abnormalities will be tested as candidates for miRNA based cancer gene therapy. PMID- 29788628 TI - Advances in understanding of the genetics of autism and learning. PMID- 29788627 TI - NAT2 polymorphisms and their influence on the pharmacology and toxicity of isoniazid in TB patients. AB - Tuberculosis is a global pandemic that threatens to overwhelm healthcare budgets in many developing countries. Despite the availability of adequate effective treatment, many patients default on treatment, experience adverse side effects from antibiotics or fail to respond rapidly and recover. Isoniazid, one of the most important first-line tuberculosis drugs, is acetylated in the liver to a variable degree in different individuals giving rise to fast, intermediate and slow acetylator phenotypes. We present the view that the acetylation status of individuals plays an important contributory role in the tuberculosis pandemic. It is important to study the acetylation alleles, and to understand isoniazid metabolism and the manner in which it could affect patient compliance, isoniazid toxicity and the emergence of drug-resistant strains of mycobacteria. PMID- 29788629 TI - Current status of applied pharmacogenetics in clinical practice. PMID- 29788630 TI - Gene-diet interactions in childhood obesity: paucity of evidence as the epidemic of childhood obesity continues to rise. AB - Childhood obesity is growing rapidly worldwide. Although there have been enormous advances in the genetic underpinnings of obesity in recent years, the pathways that lead to obesity are still not completely understood. One of the ongoing challenges is the lack of a comprehensive definition of the obese phenotype that encompasses intermediary phenotypic expressions of biological and behavioral nature. Interactions between genetic and environmental factors, including nutrient exposures and dietary behaviors, can influence the development of the obese phenotype. Specifically, genes play a decisive role in the etiology of childhood obesity under the permissive circumstances of an obesogenic environment (increase in energy intake with a decrease in physical activity). Like many diseases, the causes of obesity are complex and their investigation requires novel approaches. Given the many contributors to obesity (weight gain, weight loss, weight maintenance, variability in body composition), as well as the dynamic nature of this issue, genomic tools must continue to be employed to evaluate all dimensions of the obesity phenotype, such as biochemical characteristics, susceptibility markers, nutrient intake, feeding practices and gene-environment interactions. Fundamental knowledge of the types of genes involved and available gene-diet interaction studies in children's obesity are reviewed. Although there is a paucity of existing literature in this specific domain of childhood obesity, ongoing investigations utilizing large cohorts have potential for providing the knowledge needed for targeted interventions in the future. PMID- 29788631 TI - Pharmacogenetics of the u-opioid receptor and the treatment of addictions. AB - Evaluation of: Munafo MR, Elliot KM, Murphy MF, Walton RT, Johnstone EC: Association of the u-opioid receptor gene with smoking cessation. Pharmacogenomics J. (2007) (In Press) [1] .This well-designed study examined short- and long-term outcome data from a large clinical trial comparing nicotine replacement therapy (NRT) with placebo in order to test the association between the u-opioid receptor gene and treatment outcomes. In addition to a significant effect of NRT compared with placebo across time periods, analyses revealed a significant genotype * treatment interaction at 12-week follow-up, such that participants who were homozygous for the A allele were more likely to report smoking abstinence in the NRT condition versus placebo compared with carriers of the G allele. These results did not persist after NRT was discontinued, although its temporal contiguity to treatment suggests it is a true pharmacogenetic effect. Importantly, these findings stand in contrast to previous research in the field. Moreover, the study reported provocative interactions between gender and u opioid receptor gene status with regard to long-term treatment outcome, and between abstinence and gender with regard to changes in body mass index. Munafo and colleagues' study has a number of strengths and its overall findings underline the complex ways in which genotype, gender and body mass index may interact in smoking-cessation treatment. The significance of these findings is discussed in the context of pharmacogenetics research in the field of substance use disorders. PMID- 29788633 TI - Clinical phenome scanning. AB - Large population-based cohorts are ideal for the study of common, complex disorders because they allow characterization of gene-gene and gene-environment interactions. We propose a clinical phenome scanning approach to genotype phenotype association studies, as this approach acknowledges the heterogeneous nature of common diseases and takes advantage of the unprecedented density of phenotypic data available in population-based DNA biobanks. By analogy to genome wide scanning, the construction of a clinical phenome scan includes a complete scan of all clinically available information (housed in electronic medical records). This is done on a subject-by-subject basis and the resulting phenomes can subsequently be interrogated for association with a single allele for any given gene. By prioritizing phenotype (rather than genotype), this approach allows investigators to ask the question "Which disease is associated with a given gene?" rather than "Which gene is associated with a given disease?". PMID- 29788632 TI - Healthy People 2010 disease prevalence in the Marshfield Clinic Personalized Medicine Research Project cohort: opportunities for public health genomic research. AB - OBJECTIVES: The purpose of this study was to estimate the prevalence of Healthy People 2010 disease conditions in a large population-based cohort in central Wisconsin (WI, USA) and to consider how these conditions can be prioritized for research based on the use of healthcare services, the prevalence of various disease states and the resulting study power. METHODS: Healthy People 2010 diagnoses were estimated for participants in the Personalized Medicine Research Project (PMRP), a large population-based biobank for residents aged 18 years and older living in central Wisconsin. By interrogating the electronic medical record, three parameters were calculated for each diagnosis: mean number of concomitant diagnoses, mean number of annual clinic visits before diagnosis and mean number of clinic visits after diagnosis. RESULTS: A total of 18,239 adults enrolled in PMRP from September 2002 to May 2005 and were included in the study. They had a mean age of 49 years (standard deviation: 18.5), ranging from 18-98 years; 57% were female. At least one Healthy People 2010 disease was diagnosed in 86.4% of the participants; 13.6% had never been diagnosed with any of these conditions. The median number of diagnoses per subject was three (range: 1-15). The median number of annual visits after diagnosis was lowest for chronic obstructive pulmonary disease (9.1) and highest for sleep apnea (17.9). Subjects with a diabetic retinopathy diagnosis had the highest number of concomitant diagnoses (mean: 6.8). DISCUSSION: All of the diseases within the Healthy People 2010 list are purported to have at least some genetic component, with the exception of injuries. The PMRP cohort is large enough that diseases of public health importance can be studied in the context of a variety of clinical and environmental covariates. This database is being developed as a national resource and is particularly useful where the estimated disease prevalence is 5% or greater. For less common diseases, additional cases can be recruited from throughout the Marshfield Clinic system of care, with population-based controls selected from the main PMRP study cohort. PMID- 29788634 TI - Integrating genomics and neuromarkers for the era of brain-related personalized medicine. AB - The harsh reality is that many medical treatments do not work as expected in a significant percentage of patients, and occasionally there are serious side effects. A new paradigm of personalized medicine is emerging, which proactively tailors treatment to each individual's biological and psychological profile. The first proof-of-concept phase of personalized medicine has now been achieved. However, it has thus far focused on the use of genomic markers and on disorders of the body. The complexity of the brain is likely to require a shift from a single genetic marker focus to a more integrated approach in which additional brain-related information (neuromarkers) is taken into account. Codevelopment of genomic neuromarkers with new compounds in a personalized medicine approach will lead to increased drug R&D and treatment benefits. The emerging genomic neuromarker potential has begun to be incorporated into the template for the next version of the Diagnostic and Statistical Manual (DSM-V). The statistical power of large subject numbers in databases in general (and standardized databases in particular) provides an ideal source for elucidating the best genomic-neuromarker profiles (explaining most of the main-effects variance), which will empower a brain-related personalized medicine into mainstream clinical practice. PMID- 29788637 TI - News & Views in ... Personalized Medicine. PMID- 29788636 TI - Letter from the President. PMID- 29788638 TI - Syntropy, genetic testing and personalized medicine. AB - The concept of syntropic diseases was proposed at the beginning of the last century to emphasize the phenomenon of nonrandom co-occurrence of human disorders. Common genes underlying specific syntropic diseases were called syntropic genes. The application of this concept to contemporary genomic studies will facilitate the understanding of the molecular basis of complex diseases, provide future direction for discovering new targets for therapy and prognosis, and may even lead to the reassessment of disease classification for the practice of more precise personalized medicine. With the acceptance of the syntropic genes theory, new genetic tests, focused on markers pointing to a set of pathogenetically linked diseases rather than to a single nosology, can be developed. PMID- 29788639 TI - Individual genomes and personalized medicine: life diversity and complexity. PMID- 29788641 TI - Longitudinal study of a 9p21.3 SNP using a national electronic healthcare database. AB - AIMS: Genome-wide association studies have identified a number of SNPs associated with complex disease. The longitudinal significance of these variants is uncertain and clinical genomic studies are required to elucidate what clinical value these variants have. Linking DNA to clinical health information databases is a powerful and potentially low-cost means of performing such research. Here, we describe a proof-of-principle study demonstrating the potential of this method. MATERIALS & METHODS: A total of 376 individuals presenting to a hospital with severe coronary artery disease were enrolled into a prospective cohort study. DNA, demographic data, ethnicity and other clinical information was collected in an electronic database. Genotyping for SNPs rs2383207 and rs10757278 was performed using Sequenom(r) (CA, USA) matrix-assisted laser desorption/ionisation-time of flight mass spectrometry. Health outcomes were tracked from when patients were discharged from the hospital using the New Zealand Health Information Service (Wellington, New Zealand). RESULTS: A total of 253 (67%) patients were of New Zealand European descent, 47 (13%) patients were of Maori descent and 21 (6%) were of Pacific Island ancestry. The Maori and Pacific Island group were younger at presentation (63 +/- 11 vs 70 +/- 9 years of age; p < 0.0001) and had a higher prevalence of cardiovascular risk factors. The frequency of the at-risk rs2383207 G allele in the Maori and Pacific group was 70%, compared with 54% in Europeans (p = 0.002). Similarly, the rs10757278 G allele was also present at a higher frequency (68 vs 52%; p = 0.003). No association was seen between the rs10757278 SNP and cardiovascular risk factors or markers of disease severity. GA and GG individuals had a higher rate of cardiovascular (p = 0.04) and all-cause death (p = 0.02). CONCLUSION: The linking of genetic data to electronic medical databases is an effective tool to assess the longitudinal effect of gene variants on health outcomes and will aid in the implementation of personalized medicine. Larger sample sizes with longer study duration may yield clinically useful information that aids preventative healthcare. PMID- 29788642 TI - Personalized psychopharmacology for the affective disorders and schizophrenia: where is the evidence? AB - Individualized medicine is the ultimate aim of many medical specialties. Attempts to individualize psychopharmacology have focused on the genetic polymorphisms of neurotransmitter- and CNS-related genes. While there have been numerous reports on the discovery of possible genetic differences in various psychiatric disorders, clinical psychopharmacology has not yet significantly benefited from such data. At present, individualized psychopharmacology in practice is still largely the choice of drugs with the least side effects for a particular patient. PMID- 29788643 TI - Application of a pharmacogenetic test adoption model to six oncology biomarkers. AB - The ability of genomics to match precise information about the molecular biology of a cancer with the available present and future therapeutics offers tremendous promise for cancer patients. Unfortunately, few genomic-based tests or treatments are available today to benefit these patients. Using a pharmacogenetic test adoption model, previously introduced to model the adoption of HLA-B*5701 testing for abacavir hypersensitivity, six oncology biomarkers, HER2, BCR-ABL quantitation, KRAS mutation, UGT1A1, CYP2D6 for tamoxifen and EGFR expression, test adoption patterns are explored. Developmental milestones and emerging scientific knowledge relating to each of the biomarkers are discussed in the context of their impact on test ordering patterns. Through analysis of the adoption patterns of multiple cancer biomarkers, a pharmacogenetic model emerges which appears to be applicable in five of the six biomarkers. This model may be useful in predicting adoption patterns of new markers and in providing guidance to drug and test developers introducing personalized medicine applications. PMID- 29788644 TI - Is it prime time for personalized medicine in cancer treatment? AB - Over the last decade, with rapidly advancing biotechnology, the understanding of cancer has changed. The genomic era has resulted in an explosion of targeted therapies and prognostic and predictive biomarkers. This article aims to illustrate the advances made in the practice of oncology as well as the potential and limitations of personalized medicine in cancer. PMID- 29788645 TI - Biomarkers and their consequences for the biomedical profession: a social science perspective. AB - Although biomarkers are not altogether new, they are gaining a new life in our postgenomic present. This article takes this as a good reason to explore biomarkers in depth and to speculate about the consequences that biomarkers might engender in clinical practices. First, the article ventures into an endeavor of ordering the dynamic field of biomarkers, suggesting a possible classification of biomarkers, and then argues that we are currently witnessing a 'biomarkerization' of health and disease - defined as an ongoing future-oriented process that seeks to solve biomedical as well as public health problems through investments into biomarker research at the present time. Subsequently, this article reflects on some possible consequences of this phenomenon. It argues that while the movement of candidate biomarkers into the clinic is arduous, biomarkers might develop a life of their own once they arrive in the clinic. This article outlines the direction of two such possible consequences. It suggests that biomarkers might be involved in a change of the actors that order and categorize diseases, as well as trigger transformations in our understanding of what counts as disease in the first place. Hence, this article seeks to shed light on the paradox that while biomarkers are designed to add more evidence into clinical practice, they might actually increase uncertainty and ambiguity. PMID- 29788646 TI - Development of novel drugs for ocular diseases: possibilities for individualized therapy. AB - In clinical ophthalmology, new and old drug regimens are available for the treatment of major eye diseases, including potentially blinding conditions, such as glaucoma, and various macular diseases. In glaucoma, therapeutic treatment mainly deals with control of intraocular pressure at low levels but the clinical courses of patients can be very variable. Very often, specific drug combinations and dosages have to be formulated for individual glaucoma patients. In neovascular age-related macular degeneration, choroidal neovascularization can lead to progressive and irreversible visual impairment if not treated early. In recent years, clinical trials using photodynamic therapy with verteporfin and various anti-VEGF antibodies, such as ranibizumab and bevacizumab, have enhanced the treatment outcomes of neovascular age-related macular degeneration. In diabetic macular edema, intravitreal triamcinolone acetonide and anti-VEGF therapy are effective in some patients. Again, responses to treatment are not uniform in all macular patients. Traditional herbal medicine has long been known to play a role in the practice of personalized formulations in Asia. Potential preventive and therapeutic effects have been claimed in individual eye patients. Meanwhile, advanced technologies in molecular biology have led to identification of genes associated with many eye diseases and development of the concept of individual medicine, in which the genotype of a person can be used as a basis for disease prediction or prophylactic treatments. Moreover, pharmacogenomic studies have demonstrated the association of various genotypes or haplotypes with responses to drug therapies, providing hope for tailormade personalized treatments. The combination of genotypic information with clinical features for the prescription of treatment modes in eye diseases is under vigorous research. PMID- 29788647 TI - Role of proteomics in personalized medicine. PMID- 29788648 TI - Relocating health governance: personalized medicine in times of 'global genes'. AB - To date, governance questions related to personalized medicine - the consideration of the genetic and genomic determinants of varying drug response in patients - have been primarily addressed in terms of ethical implications. However, an analysis of the governance of personalized medicine should reach further. At present, governance issues arise in the context of an ongoing dispersion of national regulatory power. Due to the growing complexity of society, it has become impossible to govern society from a single center or by means of a single privileged governance mechanism. Governing increasingly includes the active participation of nongovernmental and individual actors by means of creating informal norms of conduct. Personalized medicine, due to its core concepts, fosters the emergence of new alliances (private and public, regional and global, for-profit and for-health) and thereby bears the promise to bridge some traditional dichotomies. Much rather than the quest for individualized drugs, it is this characteristic of personalized medicine that attracts so much attention from outside the medical and life science field. PMID- 29788649 TI - Reimbursement and coverage challenges associated with bringing emerging molecular diagnostics into the personalized medicine paradigm. AB - A simple search of the US FDA and the Centers for Medicare and Medicaid Services (CMS) websites demonstrates that the science of personalized medicine is far more advanced than current coverage and reimbursement policies. When one searches the websites of the FDA and CMS for pharmagenomics, personalized medicine and genetic testing, over 1800 hits come up on the US FDA website, and 52 hits come up on the CMS website. Although this is no surprise to those involved in the field of personalized medicine, it does illustrate the uphill battle that we face in educating policy makers on the need to appropriately cover and reimburse molecular diagnostics for use in a personalized medicine paradigm. A fully integrated personalized medicine paradigm will be driven by the ability to eliminate the reimbursement and coverage barriers that impact a patient's ability to access technological innovations in molecular diagnostic testing. For the purpose of this discussion, molecular diagnostic tests will be defined as a clinical diagnostic test performed on DNA, RNA or protein. PMID- 29788650 TI - Human Variome Project to identify all human gene mutations launched. PMID- 29788651 TI - Lay perspective on pharmacogenomics: a literature review. AB - The lay attitude to pharmacogenomics is crucial to successful implementation. The intention of the present literature review is to delineate the considerations, expectations, fears, and so on, described in the literature regarding pharmacogenomics seen from a lay perspective. The literature review was conducted in Medline and EMBASE in March 2005. The combined search in databases, reference lists, and so on, produced a total of 30 relevant articles, of which seven are included in the literature review. Other literature reviews on this issue are included in the discussion. This review documents that, at this time, very little information is available regarding the public's attitude to pharmacogenetic testing and the use of pharmacogenomics in therapy. Thus, studies of lay attitudes to and expectations of pharmacogenomics are highly relevant. Research is increasingly being conducted in the area, and studies have shown that education, income, age, ethnicity and nationality seems to influence lay attitudes. Based on this, it is concluded that knowledge of the relation between national /cross-national cultural and subcultural settings, and attitudes toward pharmacogenomics seem to be important to a successful pharmacogenomics implementation in healthcare. PMID- 29788652 TI - Genomics-based labeling and attribution: a case for integrating social sciences into personalized medicine research. AB - As the field of genomics uncovers the etiology and pathophysiological mechanisms of disease, we will gain a greater understanding of the causes of disease, leading to preventive interventions, early diagnoses and new and improved treatments. Although understanding the specific roles of environment and genetics in disease onset and development will most likely improve health outcomes, the impact of this information for the individual and public remains to be seen. Understanding what factors influence individual and public perceptions and behavioral consequences related to genome-based disease labels and attributions will be critical to a successful transition for personalized medicine. To better understand the impact of genomic-based disease labeling and attribution, social scientists need to be involved in clinical genomics studies to assess the consequences of the use of and response to new personalized diagnoses and treatments. PMID- 29788653 TI - Quality of consent forms in pharmacogenetic studies: a survey of research ethics committees in Spain. AB - OBJECTIVES: To know the quality of consent forms in pharmacogenetic studies submitted for evaluation to Research Ethics Committees (RECs). METHODS: A mail survey to RECs in Spain was conducted; this survey contained questions on the frequency with which different items were included in the consent forms of pharmacogenetic studies reviewed by each REC. RESULTS: A total of 40 out of 69 RECs that answered the questionnaire had reviewed pharmacogenetic studies. RECs considered that information was always or almost always comprehensible in approximately 50% of the forms received. Information regarding reimbursement of patients and commercial interests of the research was scarcely incorporated in the consent forms. In general, RECs estimated that aspects related to the use of samples and genetic information were included in the consent forms with a frequency lower than 50%. The quality of consent forms was considered to be lower by those RECs which had reviewed a higher number of pharmacogenetic studies. CONCLUSION: Significant deficiencies have been found in the consent forms of pharmacogenetic studies reviewed by Spanish RECs. PMID- 29788654 TI - Overview of genetic testing in cancer. AB - Until recently, hereditary tendencies toward multiple diseases, including cancer, were mainly determined by examining the family history of the affected individuals. However, the Human Genome Project has ushered in a genomics revolution and boosted the diagnostic testing industry with the emergence of genetic tests that may be used for the diagnosis and management of both inherited and noninherited malignancies. Genetic tests are already available to identify patients carrying cancer susceptibility genes and predict drug response, thus enabling physicians to carefully tailor a more personalized drug regimen that is more likely to result in a favorable outcome for the patient. However, before gene-based tests become widely available, thought leaders and society in general need to understand and discuss the major technical, ethical and economic ramifications of genetic testing. These issues are currently being reviewed by government, academia, regulatory agencies and professional societies using evidence-based principles. PMID- 29788655 TI - Molecular and cellular approaches to patient management in oncology. AB - Many of the techniques that are employed today by pathologists and oncologists to generate a diagnosis, prognosis or prediction of response have not changed over several decades. However, new molecular and cellular technologies will enable more precise and objective decision-making. This review will detail some of the more recent developments in these areas from Veridex, LLC, academic laboratories and other commercial entities. The discussion of molecular technologies will focus on breast sentinel lymph node biopsy, prostate biopsy, carcinoma of unknown primary, prediction of recurrence in lymph node negative colon and breast cancers and pharmacogenomics. The discussion of cellular technologies will focus on the use of circulating cells to serve in both prognostic and predictive capacities and on the use of molecular methods to interrogate the DNA and RNA isolated from these circulating cells. PMID- 29788656 TI - Matching patients with drugs: triumphs and challenges. AB - The foundations of personalized medicine are built on the premise that laboratory tests can accurately predict the response of individual patients to a particular treatment. Herceptin(r) and the HercepTest(r), which is used to select patients with human epidermal growth factor receptor (HER2)-positive breast cancer, are rightfully the jewels in the crown of this new treatment paradigm. Although over 8 years have past since their joint approval, there remain ongoing concerns about the quality of HER2 testing in community pathology laboratories. The development of predictive epidermal growth factor receptor (EGFR) tests for treatment with Tarceva(r), Iressa(r) and Erbitux(r) has proven more difficult due to the complex biology of the target. It has also exposed some of the business challenges of co developing both a drug and a companion diagnostic test. This article describes Genentech's experience of developing predictive tests for HER2 and EGFR and highlights the need for close collaboration between all parties involved in incorporating predictive diagnostic tests into clinical trials and clinical practice. PMID- 29788657 TI - Individualizing analgesic prescription Part I: pharmacogenetics of opioid analgesics. AB - The current use of analgesics is based on the empiric administration of a given drug with clinical monitoring for efficacy and toxicity. However, individual responses to drugs are influenced by a combination of pharmacokinetic and pharmacodynamic processes, and each of these components, in addition to pain perception and processing, seem to be regulated by genetic factors. Whereas polymorphic drug-metabolizing enzymes and drug transporters may affect the pharmacokinetics of drugs, polymorphic drug targets and disease-related pathways may influence the pharmacodynamic action of drugs. After usual dose, drug toxicity, as well as inefficacy, can be observed depending on the polymorphism, the analgesic considered and the presence or absence of active metabolites. Thus, cytochrome P450 (CYP)2D6 polymorphism influences codeine and tramadol analgesic effects, CYP2C9 has an impact on the disposition of some nonsteroidal anti inflammatory drugs, and opioid receptor polymorphism (118A>G) may reduce morphine potency. Moreover, drug interaction mimics genetic deficiency and contributes to the variability in response to analgesics. This two-part review summarizes the available data on the pharmacokinetic-pharmacodynamic consequences of known polymorphisms of drug-metabolizing enzymes (CYP and uridine diphosphate glucuronosyltransferase), drug transporters (multidrug resistance proteins, multidrug resistance-associated proteins, organic anion-transporting polypeptides, and serotonin transporters), relevant drug targets (such as u opioid receptor, serotonin receptor and cyclooxygenases) and other nonopioid biological systems, on currently prescribed central and peripheral analgesics. PMID- 29788658 TI - Individualizing analgesic prescription. Part II: pharmacogenetics of anti inflammatory analgesics and co-analgesics. PMID- 29788659 TI - Biobanking and biorepositories: looking to the future. PMID- 29788660 TI - Personalized medicine: using effective partnering for managing the risk of legal liability. AB - Beyond the economic cost-benefit analysis of incorporating pharmacogenomics into the process of drug development, it is time for the players in the industry to begin considering the long-term potential legal liabilities that may arise, and to undertake a legal analysis to identify and avoid those risks to the greatest possible extent. The current economic model being considered for pharmacogenomics technologies fails to take this legal risk into consideration, and therefore does not provide a complete picture of the incentives and disincentives of entering into this space. However, the more evenly weighted balance of all of the economic interests - costs, benefits and risks - can be tipped into the positive through effective partnering relationships between the pharmaceutical and diagnostic industries, and the diagnostic industry and pharmacy benefit managers. Such relationships will provide companies not only with needed economic incentives, but also with added protection from the potential future legal liabilities. PMID- 29788661 TI - Gene patents and personalized medicine. PMID- 29788663 TI - Eighth Asian Bioethics Conference. PMID- 29788662 TI - Searching susceptibility genes for antipsychotic-induced weight gain: is the 5 HT2C receptor gene a promising candidate? AB - Evaluation of: de Luca V, Mueller DJ, de Bartolomeis A, Kennedy JL: Association of the HTR2C gene and antipsychotic induced weight gain: a meta-analysis. Int. J. Neuropsychopharmacol. (2007) (Epub ahead print) [1] . Weight gain is a major adverse effect of the second-generation antipsychotics that are widely prescribed in psychiatric practice. Given its variability among patients and indirect evidence of its heritability, antipsychotic-induced weight gain has become a major target of pharmacogenetic studies. The protective effect of the T allele of the 5-HT2C receptor gene -759C/T promoter polymorphism on antipsychotic-induced weight gain has been repeatedly reported in independent studies. However, negative results have also been obtained, especially in subjects treated with clozapine. Recently, de Luca and colleagues investigated the association between the 5-HT2C receptor gene -759C/T promoter polymorphism and antipsychotic-induced weight gain using a meta-analytical approach [1] . The pooled data of eight studies (total 588 subjects) showed a trend of association between the -759T allele and lower weight gain, with evidence of significant between-study heterogeneity. Publication bias and the influence of confounding variables, such as age, gender, ethnicity, clozapine-treated patient proportions, durations of observation and the effect of weight gain cutoff criteria on effect size, were also evaluated in their meta-analysis. To clarify the contribution of the 5-HT2C receptor gene to a complex trait such as antipsychotic-induced weight gain, a greater number of independent studies with larger sample size that carefully consider various confounding factors and gene-environment interactions are required. PMID- 29788664 TI - New insights into the genetics of asthma. PMID- 29788666 TI - Personalizing our diet to improve our health: the potential impact of nutrigenomics. PMID- 29788667 TI - Today's research, tomorrow's health: focus on pharmacogenomics. PMID- 29788665 TI - Valuing personalized medicine: willingness to pay for genetic testing for colorectal cancer risk. AB - OBJECTIVES: Personalized medicine using genetic information is increasing in cancer screening and treatment; however, little is known about perceived value of genetic testing for cancer risk in a general population. The objectives of this report are: to identify a general population's willingness to pay for genetic testing that provids colorectal cancer risk information; examine whether screening intentions (likelihood of testing and test choice) change based on risk; and identify providers' beliefs about patients' perceived value. METHODS: A survey of US general (n = 1087) and physician (n = 100) populations using the willingness-to-pay method was carried out. Physicians responded from the perspective of a typical patient. chi2 tests, t-tests and ordered logistic regression were used to examine factors associated with willingness to pay and intentions to be screened. RESULTS: General population respondents' average willingness to pay for a genetic test for colorectal cancer risk was US$150. Higher willingness to pay was significantly associated with being male, having higher income and education, having private health insurance and reporting a greater likelihood of getting colorectal cancer screening when due. Physicians' beliefs about patients were different than general population responses: physicians believed patients would be willing to pay more (US$212; p < 0.001), fewer believed patients would not pay (1 vs 17%; p<0.001), and if a genetic test indicated higher than average risk, physicians believed patients would be more likely to get screened (65 vs 46%; p < 0.001) and would choose alternative screening tests (62 vs 22%; p < 0.001). CONCLUSION: Respondents valued genetic tests to inform screening decisions and indicated that tests may influence screening choices. Additional studies are needed to examine the implications of physicians' beliefs about patients' choices for screening. PMID- 29788668 TI - Collagen gel droplet-embedded culture drug-sensitivity test and potential for personalizing cancer treatment. AB - Sensitivity testing for general anticancer agents involves culturing cancer cells, exposure to an anticancer agent, and assessing the degree of growth inhibition. One such method is the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Clinical results confirm a close correlation of a better than 75% accuracy between CD-DST results and responses to anticancer agents administered in the clinical setting. Although there have been few randomized, controlled studies of the CD-DST method, the general observation is that cancer patients survive longer if their disease responds to an anticancer agent than if it is ineffective. Therefore, it can be extrapolated that the high diagnostic accuracy of CD-DST is indirect evidence that this method can be used to select the group for whom chemotherapy will be effective, with a resultant prolongation of their survival time, and the group for whom chemotherapy will be ineffective, with no increased survival time. PMID- 29788669 TI - Endocannabinoid system and pathophysiology of adipogenesis: current management of obesity. AB - The endocannabinoids are now known as novel and important regulators of energy metabolism and homeostasis. The endocrine functions of white adipose are chiefly involved in the control of whole-body metabolism, insulin sensitivity and food intake. Adipocytes produce hormones, such as leptin and adiponectin, that can improve insulin resistance or peptides, such as TNF-alpha, that elicit insulin resistance. Adipocytes express specific receptors, such as peroxisome proliferator-activated receptor (PPAR)-gamma, which serve as adipocyte targets for insulin sensitizers such as thiazolidinediones. Recently, endocannabinoids and related compounds were identified in human fat cells. The endocannabinoid system consists primarily of two receptors, cannabinoid (CB)1 and CB2, their endogenous ligands termed endocannabinoids and the enzymes responsible for ligand biosynthesis and degradation. The endocannabinoids 2-arachidonylglycerol and anandamide or N-arachidonoylethanolamine increase food intake and promote weight gain in animals. Rimonabant, a selective CB1 blocker, reduces food intake and body weight in animals and humans. PMID- 29788671 TI - Predictive and prognostic markers in colorectal cancer. AB - Despite recent advances in the treatment of both early and advanced colorectal cancer, it remains the second leading cause of cancer deaths in the western world. There is, therefore, a pressing need to optimize the use of the currently available systemic therapies and to identify active new agents for the treatment of this disease. Pharmacogenomic studies have shown that genetically determined variability in key cellular functions can influence toxicity, response to treatment and survival. Numerous examples of these single 'classical' markers have been identified for a wide range of agents and each has been studied with regard to its effect on response. However, in any individual or tumor it is likely that a number of complex, interacting factors are involved in determining the likelihood of benefit with a given therapeutic agent. Microarray-based gene expression profiling has allowed the complex range of molecular changes occurring in the cell and surrounding stroma to be assessed in relation to response and prognosis. Predictive gene sets have been developed and, along with other markers, are being assessed in prospective clinical trials. Treatment may soon be individualized by using this technology to predict which patients will benefit from a particular systemic therapy or which are likely to develop recurrence. PMID- 29788670 TI - Personalized medicine for eradication of Helicobacter pylori. AB - Regimens for eradication of Helicobacter pylori consist of a proton-pump inhibitor (PPI) and one or two antimicrobial agents, such as amoxicillin, clarithromycin or metronidazole. As the pharmacokinetics and pharmacodynamics of PPIs are affected by polymorphism of CYP2C19, doses and dosing schemes of a PPI should be optimized based on genotype status of each patient in order to yield higher eradication rates. PPIs affect the pharmacokinetics of other substrates of CYP2C19, such as warfarin and diazepam. Acid inhibition induced by a PPI also affects the pharmacokinetics of some drugs, such as itraconazole. Clarithromycin, one of the most frequently used antimicrobial agents in eradication of H. pylori, inhibits activity of CYP3A4, meaning that the pharmacokinetics of substrates of CYP3A4 are affected by clarithromycin. Therefore, clinicians must pay attention to the other drugs dosed to each of their patients. Therefore, the eradication regimen for H. pylori infection should be designed with the CYP2C19 genotype status, bacterial susceptibility to antimicrobial agents, and other drugs being taken by each patient having been taken into consideration. PMID- 29788672 TI - Monogenic disorders of the pancreatic beta-cell: personalizing treatment for rare forms of diabetes and hypoglycemia. AB - Over the past 10-20 years, our understanding of the genetic etiology of monogenic disorders of the pancreatic beta-cell has greatly improved. This has enabled clinicians to provide patients with more accurate information regarding prognosis and inheritance and has influenced treatment. Maturity-onset diabetes of the young and neonatal diabetes are two such examples. Patients with maturity-onset diabetes of the young due to glucokinase mutations can usually be managed by diet alone, while those affected by HNF-1alpha and HNF-4alpha mutations respond well to low doses of sulfonylureas. The identification of mutations in the ATP dependent potassium channel genes KCNJ11 and ABCC8 as the most common cause of permanent neonatal diabetes has improved treatment regimes for affected children. In addition to enabling patients to stop insulin injections, their glycemic control has also improved. These advances show the importance of unravelling the genetics of a disease to achieve the best individualized treatment for the patients affected. PMID- 29788673 TI - Pharmacogenetics of risperidone response and induced side effects. AB - Risperidone is an atypical antipsychotic that has been effectively used to treat several psychiatric diseases. Atypical antipsychotics present some advantages over conventional antipsychotics, primarily because they offer effective treatment alternatives that are relatively free of extrapyramidal symptoms. However, as with all antipsychotics, there are wide individual differences in response to risperidone, both regarding therapeutic effects and adverse effects, imposing some limitations with respect to the therapeutic use of the drug. Genetic factors are thought to play an important role in determining the variability to drug response. A growing number of studies are investigating how genetic polymorphisms of enzymes involved in drug metabolism or of receptors targeted by antipsychotic agents influence drug treatment of several neuropsychiatric diseases. In this article we will review the genetic variability in both the pharmacokinetics of risperidone action and in pharmacodynamic structures mediating risperidone effects, as well as the pharmacogenetic studies performed for these genes. PMID- 29788674 TI - Genetic-based therapies to select nonpathogenic variants of HIV-1. AB - Lentiviral-based genetic therapies offer a valuable addition to the current anti HIV arsenal and allow for a rational directed approach to evolve HIV-1 to a less pathogenic state. Many lentiviral vector systems have been described that can be either replication incompetent, self-inactivating or conditionally replicating. Importantly, lentiviral vectors can be engineered to deliver anti-HIV-1 genes such as antisense RNAs, aptamers and siRNAs to those cells involved in HIV-1 infection: T-cells, hematopoietic stem cells and dendritic cells. Furthermore, the use of HIV-2-based vectors that can be mobilized by wild-type HIV-1 in vivo and spread to those cells targeted by the virus, as well as compete with HIV-1 viral RNA for packaging and access to viral proteins such as Tat and Rev required for viral replication, are of special interest. This review will focus on the rational design of therapeutic lentiviral vectors that can be used in combination with current antiretroviral therapies to essentially direct the evolution of HIV 1 to a less pathogenic state of existence. PMID- 29788677 TI - Utility of topical epinephrine for determining the resection range of eyelid sebaceous carcinoma with dermatitis. PMID- 29788676 TI - Trends in statistical methods in articles published in Archives of Plastic Surgery between 2012 and 2017. AB - This review article presents an assessment of trends in statistical methods and an evaluation of their appropriateness in articles published in the Archives of Plastic Surgery (APS) from 2012 to 2017. We reviewed 388 original articles published in APS between 2012 and 2017. We categorized the articles that used statistical methods according to the type of statistical method, the number of statistical methods, and the type of statistical software used. We checked whether there were errors in the description of statistical methods and results. A total of 230 articles (59.3%) published in APS between 2012 and 2017 used one or more statistical method. Within these articles, there were 261 applications of statistical methods with continuous or ordinal outcomes, and 139 applications of statistical methods with categorical outcome. The Pearson chi-square test (17.4%) and the Mann-Whitney U test (14.4%) were the most frequently used methods. Errors in describing statistical methods and results were found in 133 of the 230 articles (57.8%). Inadequate description of P-values was the most common error (39.1%). Among the 230 articles that used statistical methods, 71.7% provided details about the statistical software programs used for the analyses. SPSS was predominantly used in the articles that presented statistical analyses. We found that the use of statistical methods in APS has increased over the last 6 years. It seems that researchers have been paying more attention to the proper use of statistics in recent years. It is expected that these positive trends will continue in APS. PMID- 29788675 TI - Anti-Tumor Necrosis Factor Therapy in Intestinal Behcet's Disease. AB - Intestinal Behcet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behcet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor alpha, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behcet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti tumor necrosis factor-alpha for the treatment of intestinal Behcet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behcet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-alpha, including vulnerability to infections and malignancy. PMID- 29788678 TI - Treatment of refractory groin lymphocele by surrounding supermicrosurgical lymphaticovenous anastomosis. PMID- 29788679 TI - Delayed bipedicled nasolabial flap in facial reconstruction. AB - BACKGROUND: The nasolabial flap is ideal for reconstruction of the nasal alar subunit due to its proximity, color and contour match, and well-placed donor scar. When raised as a random-pattern flap, there is a risk of vascular compromise to the tip with increased flap length and aggressive flap thinning. Surgical delay can greatly improve the chances of tip survival, allowing the harvest of longer flaps with greater reach. METHODS: We describe our technique of lengthening the nasolabial flap through multiple delay procedures. A bipedicled flap was first raised and then transferred as a unipedicled flap with a 6:1 length-to-width ratio. During the delay process, the flap tip was thinned to the subdermal layer. RESULTS: In our case series of seven patients, defects as far as the medial canthal area and contralateral ala were reconstructed successfully with no incidence of tip necrosis or flap loss. The resultant flaps were thin enough to be folded over for the reconstruction of alar rim defects. CONCLUSIONS: We highlight the success of our surgical technique in creating thin and robust nasolabial flaps for the reconstruction of full-thickness defects around the nose. PMID- 29788680 TI - Two sequential free flaps for coverage of a total knee implant. AB - Knee revision arthroplasty following peri-prosthetic joint infections is a formidable challenge. Patients are at a high risk of recurrent infection, and the soft tissue over the revised implant is often of questionable quality. Flap reconstruction has improved the salvage rates of infected arthroplasties, and should be considered in all cases of revision arthroplasty. We present a challenging case requiring staged reconstruction with two free latissimus dorsi flaps after the initial use of a medial gastrocnemius flap. PMID- 29788681 TI - Use of the facial dismasking flap approach for surgical treatment of a multifocal craniofacial abscess. AB - The decision of which surgical approach to use for the treatment of a multifocal craniofacial abscess is still a controversial matter. A failure to control disease progress in the craniofacial region can potentially put the patient's life at risk. Therefore, understanding the various ways to approach the craniofacial region helps surgeons to obtain satisfactory results in such cases. In this report, we describe a patient who visited the emergency department with a large swelling in his right cheek. A blood test and computed tomography revealed odontogenic maxillary sinusitis. The patient developed sepsis due to a progressive multifocal abscess. An abscess was seen in the temporal muscle, infratemporal fossa, and interorbital region. To control this multifocal abscess, we used the facial dismasking flap (FDF) approach. After debridement using the FDF approach, we succeeded in obtaining sufficient drainage of the abscess, and the patient recovered from sepsis. The advantages of the FDF approach are that it provides a wide surgical field, extending from the parietal region to the mid facial region, and that it leaves no aesthetically displeasing scars on the face. The FDF approach may be one of the best options to approach multifocal abscesses in the craniofacial region. PMID- 29788682 TI - Immediate breast reconstruction following nipple-sparing mastectomy in an Asian population: Aesthetic outcomes and mitigating nipple-areolar complex necrosis. AB - BACKGROUND: Nipple-sparing mastectomies (NSMs) are increasingly performed to obtain the best aesthetic and psychological outcomes in breast cancer treatment. However, merely preserving the nipple-areolar complex (NAC) does not guarantee a good outcome. Darkly pigmented NACs and a tendency for poor scarring outcomes are particular challenges when treating Asian patients. Herein, we review the reconstructive outcomes following NSM at Singapore General Hospital. METHODS: All breasts reconstructed following NSM over an 11-year period from 2005 to 2015 were reviewed. Information was collected from the patients' records on mastectomy indications, operative details, and complications. Patient satisfaction, breast sensation, and aesthetic outcomes were evaluated in 15 patients. Sensation was quantified using the Semmes-Weinstein monofilament test. RESULTS: A total of 142 NSMs were performed in 133 patients for breast cancer (n=122, 85.9%) or risk reduction (n=20, 14.1%). Of the procedures, 114 (80.2%) were autologous reconstructions, while 27 (19.0%) were reconstructions with implants. Complications occurred in 28 breasts (19.7%), with the most common complication being NAC necrosis, which occurred in 17 breasts (12.0%). Four breasts (2.8%) had total NAC necrosis. The overall mean patient satisfaction score was 3.0 (good). The sensation scores were significantly diminished in the skin envelope, areola, and nipple of breasts that had undergone NSM compared to non-operated breasts (P<0.05). Half of the subset of 15 patients in whom aesthetic outcomes were evaluated had reduced nipple projection. CONCLUSIONS: Immediate reconstruction after NSM was performed with a low complication rate in this series, predominantly through autologous reconstruction. Patients should be informed of potential drawbacks, including NAC necrosis, reduced nipple projection, and diminished sensation. PMID- 29788683 TI - Definitions of groove and hollowness of the infraorbital region and clinical treatment using soft-tissue filler. AB - Clarification is needed regarding the definitions and classification of groove and hollowness of the infraorbital region depending on the cause, anatomical characteristics, and appearance. Grooves in the infraorbital region can be classified as nasojugal grooves (or folds), tear trough deformities, and palpebromalar grooves; these can be differentiated based on anatomical characteristics. They are caused by the herniation of intraorbital fat, atrophy of the skin and subcutaneous fat, contraction of the orbital part of the orbicularis oculi muscle or squinting, and malar bone resorption. Safe and successful treatment requires an optimal choice of filler and treatment method. The choice between a cannula and needle depends on various factors; a needle is better for injections into a subdermal area in a relatively safe plane, while a cannula is recommended for avoiding vascular compromise when injecting filler into a deep fat layer and releasing fibrotic ligamentous structures. The injection of a soft-tissue filler into the subcutaneous fat tissue is recommended for treating mild indentations around the orbital rim and nasojugal region. Reducing the tethering effect of ligamentous structures by undermining using a cannula prior to the filler injection is recommended for treating relatively deep and fine indentations. The treatment of mild prolapse of the intraorbital septal fat or broad flattening of the infraorbital region can be improved by restoring the volume deficiency using a relatively firm filler. PMID- 29788684 TI - Evaluation of the donor site after the median forehead flap. AB - BACKGROUND: Forehead flaps are useful for facial reconstruction. Studies of these flaps have mostly focused on the results of the reconstruction. However, due to the scarring and changes on the forehead caused by the median forehead flap (MFF), surgeons may be reluctant to perform this flap. Research into the donor site is needed for practical purposes. METHODS: We examined 42 patients who underwent an MFF at Pusan National University Hospital from 1996 to 2016. Based on a retrospective chart review, we examined the occurrence of complications. We also evaluated scars on the forehead using the Vancouver Scar Scale (VSS) and assessed changes in the eyebrow position of 22 patients. RESULTS: No complications occurred in the 42 patients. The mean VSS score of the 22 patients was 2.8+/-0.79. The ratio of the height of the eyebrow on each side to the distance between the medial canthi increased postoperatively, meaning that both the left and right brows were elevated slightly (P=0.026 and P=0.014). However, the symmetry between the left and right sides did not change (P=0.979). The ratio of the interbrow distance to the distance between the medial canthi decreased slightly, meaning that the interbrow distance narrowed mildly (P<0.001). Moreover, there were no noticeable changes in the brow position as seen in a photo overlay. CONCLUSIONS: There were no notable complications in the forehead. Forehead scarring was acceptable. No change in brow symmetry was observed via photographic measurements and a photo overlay. Therefore, we propose that the MFF is a useful choice for minimizing scarring or deformation of the donor site. PMID- 29788685 TI - The lateral intercostal artery perforator as an alternative donor vessel for free vascularized lymph node transplantation. AB - Chronic lymphedema is caused by an impairment of the lymphatic system due to primary or secondary causes. Vascularized lymph node transplantation (VLNT) is currently the most promising and frequently used technique besides lymphaticovenous anastomosis. However, the vessel anatomy in the lateral thoracic region is sometimes quite variable. Based on our experiences with vascular anatomical inconstancy in the lateral thoracic region, we planned a lateral intercostal artery perforator flap for VLNT in a female patient with chronic stage II lymphedema of both legs after cervical cancer treatment. After surgery, the patient reported significant improvement in limb volume and the accompanying symptoms. The limb circumference was reduced by an average of 19.2% at 6 months postoperatively. Despite having a short pedicle and small vessel caliber, the lateral intercostal artery perforator flap can safely be used for VLNT in lymphedema patients with anatomical variants. PMID- 29788686 TI - Augmented reality and dynamic infrared thermography for perforator mapping in the anterolateral thigh. AB - Dynamic infrared thermography (DIRT) has been used for the preoperative mapping of cutaneous perforators. This technique has shown a positive correlation with intraoperative findings. Our aim was to evaluate the accuracy of perforator mapping with DIRT and augmented reality using a portable projector. For this purpose, three volunteers had both of their anterolateral thighs assessed for the presence and location of cutaneous perforators using DIRT. The obtained image of these "hotspots" was projected back onto the thigh and the presence of Doppler signals within a 10-cm diameter from the midpoint between the lateral patella and the anterior superior iliac spine was assessed using a handheld Doppler device. Hotspots were identified in all six anterolateral thighs and were successfully projected onto the skin. The median number of perforators identified within the area of interest was 5 (range, 3-8) and the median time needed to identify them was 3.5 minutes (range, 3.3-4.0 minutes). Every hotspot was correlated to a Doppler sound signal. In conclusion, augmented reality can be a reliable method for transferring the location of perforators identified by DIRT onto the thigh, facilitating its assessment and yielding a reliable map of potential perforators for flap raising. PMID- 29788687 TI - Trends in breast reconstruction: Implications for the National Health Insurance Service. AB - BACKGROUND: Breast reconstruction has become more common as mastectomy has become more frequent. In Korea, the National Health Insurance Service (NHIS) began covering breast reconstruction in April 2015. This study aimed to investigate trends in mastectomy and breast reconstruction over the past 10 years and to evaluate the impact of NHIS coverage on breast reconstruction. METHODS: Nationwide data regarding mastectomy and breast reconstruction were collected from the Korean Breast Cancer Society registry database. Multiple variables were analyzed in the records of patients who underwent breast reconstruction from January 2005 to March 2017 at a single institution. RESULTS: At Seoul National University Hospital, the total number of reconstruction cases increased 13-fold from 2005 to 2016. The proportion of immediate breast reconstruction (IBR) cases out of all cases of total mastectomy increased from 4% in 2005 to 52.0% in 2016. The proportion of delayed breast reconstruction (DBR) cases out of all cases of breast reconstruction and the overall number of DBR cases increased from 8.8% (20 cases) in 2012 to 18.3% (76 cases) in 2016. After NHIS coverage was initiated, the proportions of IBR and DBR showed statistically significant increases (P<0.05). Among the IBR cases, the percentage of prosthesis-based reconstructions increased significantly (P<0.05), but this trend was not found with DBR. Total mastectomy became significantly more common after the expansion of NHIS coverage (P<0.05). CONCLUSIONS: Over the last decade, there has been an increase in mastectomy and breast reconstruction, and the pace of increase accelerated after the expansion of NHIS coverage. It is expected that breast reconstruction will be a routine option for patients with breast cancer under the NHIS. PMID- 29788688 TI - Effectiveness of double tie-over dressing compared with bolster dressing. AB - BACKGROUND: Skin grafting is a commonly performed operation in plastic and reconstructive surgery. The tie-over dressing is an effective technique to secure the grafted skin by delivering persistent downward pressure. However, if an additional dressing is required due to incomplete graft healing, the process of re-implementing the tie-over dressing may be frustrating for both patients and surgeons. Therefore, we introduce the double tie-over dressing, which readily allows for an additional tie-over dressing after the first dressing, and we present a comparison of its effectiveness with that of the simpler bolster dressing. METHODS: Of 128 patients with a skin defect, 69 received a double tie over dressing and 59 patients received a simple bolster dressing. Using the independent t-test, the mean healing time, which was defined as the mean time it took for the wound to heal completely so that no additional dressing was required and it was washable with tap water, was compared between the 2 groups in both the head and neck region and in other areas. RESULTS: The mean healing time for the head and neck region in the double tie-over dressing group was 9.19+/-1.78 days, while it was 11.05+/-3.85 days in the bolster dressing group. The comparison of the 2 groups by the independent t-test revealed a P-value of 0.003 for the mean healing time. CONCLUSIONS: In the head and neck area, the double tie-over dressing required less time to heal than the simple bolster dressing. PMID- 29788689 TI - Weight analysis of mastectomy specimens and abdominal flaps used for breast reconstruction in Koreans. AB - BACKGROUND: Slim patients or those with large breasts may be ineligible for breast reconstruction with an abdominal flap, as the volume of the flap may be insufficient. This study aimed to establish that abdominal tissue-based breast reconstruction can be well suited for Korean patients, despite their thin body habitus. METHODS: A total of 252 patients who underwent postmastectomy breast reconstruction with an abdominal flap from October 2006 to May 2013 were retrospectively reviewed. The patients' age and body mass index were analyzed, and a correlation analysis was performed between the weight of the mastectomy specimen and that of the initial abdominal flap. RESULTS: The average weights of the mastectomy specimen and initial abdominal flap were 451.03 g and 644.95 g, respectively. The ratio of the weight of the mastectomy specimen to that of the initial flap was 0.71+/-0.23. There was a strong positive linear relationship between the weight of the mastectomy specimen and that of the initial flap (Pearson correlation coefficient, 0.728). Thirty nulliparous patients had a final to-initial flap weight ratio of 0.66+/-0.11. The 25 patients who underwent a contralateral procedure had a ratio of 0.96+/-0.30. The adjusted ratio of the final flap weight to the initial flap weight was 0.66+/-0.12. CONCLUSIONS: Breast weight had a strong positive relationship with abdominal flap weight in Koreans. Abdominal flaps provided sufficient soft tissue for breast reconstruction in most Korean patients, including nulliparous patients. However, when the mastectomy weight is estimated to be >700 g, a contralateral reduction procedure may be considered. PMID- 29788690 TI - Upper eyelid platinum weight placement for the treatment of paralytic lagophthalmos: A new plane between the inner septum and the levator aponeurosis. AB - BACKGROUND: The most common surgical treatment for paralytic lagophthalmos is the placement of a weight implant in the upper eyelid; however, this technique confers the risks of implant visibility, implant extrusion, and entropion. In this study, we present a new technique of placing platinum weight implants between the levator aponeurosis and inner septum to decrease such complications. METHODS: A total of 37 patients with paralytic lagophthalmos were treated between March 2014 and January 2017 with platinum weight placement (mean follow-up, 520.1 days). After dissecting through the orbicularis oculi muscle, the tarsal plate and levator aponeurosis were exposed. The platinum weights (1.0-1.4 g) were fixed to the upper margin of the tarsal plate and placed underneath the orbital septum. RESULTS: Five patients could partially close their eye after surgery. The average distance between the upper eyelid and the lower eyelid when the eyes were closed was 1.12 mm. The rest of the patients were able to close their eye completely. Three patients patient developed allergic conjunctivitis after platinum weight insertion, which was managed with medication. None of the patients complained of discomfort in the upper eyelid after surgery. Visibility or extrusion of the implant were observed in three patients. CONCLUSIONS: Postseptal weight placement is a safe and reproducible method in both primary and secondary upper eyelid surgery for patients with paralytic lagophthalmos. It is a feasible method for preventing implant visibility, implant exposure, and entropion. Moreover, platinum is a better implant material than gold because of its smaller size and greater thinness. PMID- 29788691 TI - A novel concept for determining the direction of implanted hair in hairline correction surgery in East Asian women. PMID- 29788692 TI - Archives of Korean Plastic Surgery. PMID- 29788693 TI - Treatment Using the SpyGlass Digital System in a Patient with Hepatolithiasis after a Whipple Procedure. AB - An 89-year-old man was referred to our hospital for treatment of hepatolithiasis causing recurrent cholangitis. He had undergone a prior Whipple procedure. Computed tomography demonstrated left-sided hepatolithiasis. First, we conducted peroral direct cholangioscopy (PDCS) using an ultraslim endoscope. Although PDCS was successfully conducted, it was unsuccessful in removing all the stones. The stones located in the B2 segment were difficult to remove because the endoscope could not be inserted deeply into this segment due to the small size of the intrahepatic bile duct. Next, we substituted the endoscope with an upper gastrointestinal endoscope. After positioning the endoscope, the SpyGlass digital system (SPY-DS) was successfully inserted deep into the B2 segment. Upon visualizing the residual stones, we conducted SPY-DS-guided electrohydraulic lithotripsy. The stones were disintegrated and completely removed. In cases of PDCS failure, a treatment strategy using the SPY-DS can be considered for patients with hepatolithiasis after a Whipple procedure. PMID- 29788694 TI - Long-term rivaroxaban for the treatment of acute venous thromboembolism in patients with active cancer in a prospective multicenter trial. AB - Background/Aims: Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. Methods: In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. Results: Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. Conclusions: Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer. PMID- 29788695 TI - Usefulness of indirect open reduction via a transconjunctival approach for the treatment of nasal bone fracture associated with orbital blowout fracture. AB - BACKGROUND: Nasal fracture and orbital blowout fracture often occur concurrently in cases of midface blunt trauma. Generally, these multiple fractures treatment is surgery, and typically, the nasal bone and orbit are operated on separately. However, we have found that utilizing a transconjunctival approach in patients with concurrent nasal bone fracture and orbital blowout fracture is a useful method. METHODS: The participants in the present study included 33 patients who visited the Plastic Surgery outpatient department between March 2014 and March 2017 and underwent surgery for nasal fracture and orbital blowout fracture. We assessed patients' and doctors' satisfaction with surgical outcomes after indirect open reduction via a transconjunctival approach for the treatment of nasal bone fracture with associated orbital blowout fracture. RESULTS: According to the satisfaction scores, both patients and doctors were satisfied with transconjunctival approach. CONCLUSION: We presented here that our method enables simultaneous operation of nasal fracture accompanied by orbital blowout fracture, rather than treating the two fractures separately, and it allows precise reduction of the nasal fracture by direct visualization of the fracture site without any additional incisions or difficult surgical techniques. Also, by preventing the use of excessive force during reduction, this method can minimize damage to the nasal mucosa, thereby reducing the incidence of nasal bleeding. PMID- 29788696 TI - Forehead reconstruction with a custom-made three-dimensional titanium implant in a Parry-Romberg syndrome patient. AB - Parry-Romberg syndrome is a rare neurocutaneous syndrome characterized by progressive shrinkage and degeneration of the tissues usually on only one side of the face. It is usually difficult to restore the facial contour due to skin tightness. In this case report, we report a forehead reconstruction with custom made three-dimensional (3D) titanium implant of a Parry-Romberg syndrome patient who was treated with multiple fat grafts but had limited effect. A 36-year-old man presented with hemifacial atrophy. The disease progressed from 5 to 16 years old. The patient had alopecia on frontal scalp and received a surgery using tissue expander. The alopecia lesion was covered by expanded scalp flap done 22 years ago. Also, he was treated with fat grafts on depressed forehead 17 years ago. However, it did not work sufficiently, and there was noted depressed forehead. We planned to make 3D titanium implant to cover the depressed area (from the superior orbital rim to the vertex). During the operation, we confirmed that the custom-made 3D implant accurately fit for the depressed area without any dead spaces. Previously depressed forehead and glabella were elevated, and the forehead contour was improved cosmetically. A custom-made 3D titanium implant is widely used for skull reconstruction and bring good results. In our case, the depressed forehead of a Parry-Romberg syndrome patient was improved by a 3D titanium implant. PMID- 29788697 TI - Natural Course of Posttraumatic Symptoms in Late-Adolescent Maritime Disaster Survivors: Results of A 12-Month Follow-Up Study. AB - Objective: This study is a prospective observational study on 75 late-adolescent survivors of a large passenger ship accident from immediately after the accident to one year later. Methods: Assessments of student survivors were conducted on day 2 and at months 1, 6, and 12. The PTSD Checklist (PCL), Patient Health Questionnaire-9 (PHQ-9), State subscale of the State and Trait Anxiety Inventory (STAI-S), Athens Insomnia Scale (AIS), and Brief Resilience Scale (BRS) were administered. Results: When the assessments for day 2 and month 12 were compared, all the scales, except the PCL-avoidance subscale, showed a significant improvement in symptoms among males. However, among females, all the scales, except the PCL-re-experience subscale and the STAI-S, failed to show a significant improvement. All the symptoms for both males and females showed a pattern that decreased to the lowest level at month 1 (camp-based controlled intervention period), then increased at months 6 and 12 (voluntary individual treatment after returning to school). Conclusion: The rapid deterioration of psychological symptoms was found during the chronic phase, when students returned to their daily routines and received voluntary individual therapy. There is a need to screen high-risk adolescents and be more attentive to them during this period. PMID- 29788698 TI - Electronic Media Exposure and Use among Toddlers. AB - Objective: These days, young children are exposed to a wide range of smart devices and their usage of smart devices is rapidly increasing worldwide. However, the use of smart devices by young children has not been studied in detail yet because smart device is relatively recent. The purpose of this study was to investigate the exposure status of smart devices among 2-5 years old children in Korea. Methods: Four hundred parents of 2- to 5-year-old children were invited to enroll. Data on demographic information and the frequency of media use, time of media use, age at first use of media was self-reported. Results: Among 390 toddlers, 39.3% watched TV almost every day, while 12.0% of children used smartphone on a daily basis. During weekdays, 48% of the children watched TV for over an hour. On weekends, 63.1% of the children watched TV for over an hour. On weekends, 23.4% of children use their smartphones for over an hour. Children using smartphones before 24 months of age were 31.3%. Conclusion: Research has shown that TV and smartphones are the most popular digital devices used by toddlers. Most toddlers began using smart devices at 12-24 months. This study provides comprehensive information on children's contemporary use of media. PMID- 29788700 TI - Cardiovascular Risk Prediction in Korean Adults. PMID- 29788699 TI - Psychiatric Disorders and Recidivism among Korean Adolescents on Probation or Parole. AB - Objective: The percentage of repeat offenders is increasing among juvenile offenders in Korea. The assessment and treatment of the mental health of young offenders may play an important role in reducing the recidivism rate of adolescents. This study examined the prevalence of psychiatric disorders among adolescents on probation or parole and the risk of recidivism associated with specific psychiatric disorders. Methods: We studied 120 adolescents on probation. The Mini-International Neuropsychiatric Interview and Conners' Rating Scale Revised were used to diagnose psychiatric disorders. Results: Almost half of the juvenile offenders had psychiatric disorders, including alcohol use disorder (19.17%), bipolar disorder (18.33%), antisocial personality disorder (11.67%), and attention-deficit/hyperactivity disorder (10.83%). Alcohol use disorder was significantly associated with repeated offenses, but psychiatric disorders, excluding alcohol use disorder, were not significantly associated with repeated offenses. Conclusion: These results suggested that the development of education and treatment programs for psychiatric disorders, including alcohol use disorder, among juvenile offenders on probation or parole may help to prevent repeated criminal behaviour. PMID- 29788702 TI - The Prevalence of Gallstone Disease Is Significantly Lower in Natives than in Migrants of Jeju Island. AB - BACKGROUND: The eating habits of Jeju Island natives are quite different from those of the mainland people because of geographic isolation. Diet is a main factor affecting gallstone disease. We investigated the prevalence of gallstone disease in both Jeju Island natives and migrants and studied the risk factors affecting gallstone disease in the Jeju Island people. METHODS: A total of 20,763 subjects who underwent medical checkups at the Health Promotion Center of Jeju National University Hospital in Korea from January 2003 to December 2015 were enrolled in the study. Ultrasonography was used to determine the presence of gallbladder stones. Body mass index and biochemical parameters, including liver function test results, lipid profiles, and fasting blood glucose levels, were verified, and data on age, birthplace, and sex were collected from medical records. Univariate and multivariate analyses were performed to identify risk factors affecting gallstone disease. RESULTS: The prevalence of gallstone disease in the Jeju Island people was 4.0%: Jeju Island natives, 3.8% and migrants, 4.4% (P=0.047). After multivariate logistic regression analysis, the independent risk factors were older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower high-density lipoprotein cholesterol levels. CONCLUSION: The prevalence of gallstone disease was significantly lower in natives than in migrants from Jeju Island. Older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower highdensity lipoprotein cholesterol levels contributed to gallstone disease prevalence in the Jeju Island people. PMID- 29788701 TI - The Bidirectional Relationship between Diabetes and Depression: A Literature Review. AB - Diabetes is a major public health problem worldwide. Depression is a serious mental condition that decreases mental and physical functioning and reduces the quality of life. Several lines of evidence suggest a bidirectional relationship between diabetes and depression: diabetes patients are twice as likely to experience depression than nondiabetic individuals. In contrast, depression increases the risk of diabetes and interferes with its daily self-management. Diabetes patients with depression have poor glycemic control, reduced quality of life, and an increased risk of diabetes complications, consequently having an increased mortality rate. Conflicting evidence exists on the potential role of factors that may account for or modulate the relationship between diabetes and depression. Therefore, this review aims to highlight the most notable body of literature that dissects the various facets of the bidirectional relationship between diabetes and depression. A focused discussion of the proposed mechanisms underlying this relationship is also provided. We systematically reviewed the relevant literature in the PubMed database, using the keywords "Diabetes AND Depression". After exclusion of duplicate and irrelevant material, literature eligible for inclusion in this review was based on meta-analysis studies, clinical trials with large sample sizes (n>=1,000), randomized clinical trials, and comprehensive national and cross-country clinical studies. The evidence we present in this review supports the pressing need for long, outcome-oriented, randomized clinical trials to determine whether the identification and treatment of patients with these comorbid conditions will improve their medical outcomes and quality of life. PMID- 29788703 TI - Effects of Age at First Childbirth and Other Factors on Central Obesity in Postmenopausal Women: The 2013-2015 Korean National Health and Nutrition Examination Survey. AB - BACKGROUND: Waist circumference is one of the key components of metabolic syndrome. Recent studies demonstrated that the reproductive profile was associated with metabolic syndrome in postmenopausal women. This study focused on the association between central obesity and age at first childbirth. It also considered other factors associated with central obesity in postmenopausal women. METHODS: This study was based on the 2013-2015 Korean National Health and Nutrition Examination Survey and involved 3,143 naturally postmenopausal women. These women were divided into three groups according to their age at first childbirth: 19 years or younger (n=252), 20-29 years (n=2,695), and 30 years or older (n=196). Multivariate analysis using logistic regression was performed to evaluate the effects of various reproductive factors, including other confounding factors. RESULTS: During adjustment for confounding factors, in the early age at first childbirth group, odds ratios (95% confidence intervals) for central obesity decreased. In the final model, younger age at first childbirth was not significantly related to central obesity (waist circumference more than 85 cm) in naturally postmenopausal women after adjusting for other confounding factors. CONCLUSION: Younger age at first childbirth was not significantly associated with central obesity after adjustment for confounding factors. PMID- 29788704 TI - Low Estimated Glomerular Filtration Rate Is Prevalent among North Korean Refugees in South Korea. AB - BACKGROUND: The number of North Korean refugees entering South Korea is rising. Few studies have investigated the risk of non-communicable disease in North Korean refugees. Moreover, kidney insufficiency, a risk factor for cardiovascular disease, has not been studied in this population. We compared the prevalence of non-communicable disease and kidney function in North Korean refugees and South Koreans. METHODS: Our study was conducted using a case-control design. We enrolled 118 North Korean refugees from the Hana Center and selected 472 randomly sampled South Korean individuals as controls, who were age- and sex-matched with the North Korean refugees in a ratio of 1:4, from the 2014 Korea National Health and Nutrition Examination Survey database. RESULTS: The prevalence of non communicable disease did not differ significantly between the groups; however, a low estimated glomerular filtration rate (eGFR; <90 mL/min per 1.73 m2) was more prevalent in the North Korean refugees than in the South Korean population (52.1% vs. 29.9%, P<0.001). After adjusting for covariates and weight gain after escape, the prevalence of a low eGFR was associated with the length of residence in South Korea (odds ratio, 2.84; 95% confidence interval, 1.02-7.89). CONCLUSION: The prevalence of non-communicable disease did not differ between North Korean refugees and the South Korean population, while a low eGFR was more prevalent in North Korean refugees than in South Koreans. Moreover, after adjusting for other covariates, the prevalence of a low eGFR in North Korean refugees was associated with the length of residence in South Korea. PMID- 29788705 TI - The Risk of Microalbuminuria by Obesity Phenotypes according to Metabolic Health and Obesity: The Korean National Health and Nutrition Examination Survey 2011 2014. AB - BACKGROUND: The present study aimed at identifying the difference in the risk of microalbuminuria among individuals with various obesity phenotypes in terms of metabolic health and obesity. METHODS: This cross-sectional study included 15,268 individuals and used data from the National Health and Nutrition Survey conducted from 2011 to 2014. Obesity was defined as body mass index >=25 kg/m2. Metabolically unhealthy was defined as meeting two or more of the following criteria: systolic and diastolic blood pressure >=130/85 mm Hg or current use of hypertensive drugs; triglyceride level >=150 mg/dL; high-density lipoprotein level <40/50 mg/dL (in both men and women); and fasting blood glucose level >=100 mg/dL or current use of oral antidiabetic medications. The participants were further classified into four subgroups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). RESULTS: A significant difference was observed in the microalbuminuria ratio among the four groups. The MHNO group was considered as the reference group, and the MHO, MUNO, and MUO groups were at an increased risk for microalbuminuria by 1.42 fold (95% confidence interval [95% CI], 1.03-1.96), 2.02 fold (95% CI, 1.61-2.53), and 3.40 fold (95% CI, 2.70 4.26), respectively, after adjusting confounding factors. CONCLUSION: The MUNO group had a higher risk of developing microalbuminuria than the MHNO group. Thus, based on this result, differences were observed in the risk of developing microalbuminuria among individuals with various obesity subtypes. PMID- 29788706 TI - The Association between 10-Year Atherosclerotic Cardiovascular Diseases Risk Score Calculated Using 2013 American College of Cardiology/American Heart Association Guidelines and Serum 25-Hydroxyvitamin D Level among Aged 40-79 Years in Korea: The Sixth Korea National Health and Nutrition Examination Surveys. AB - BACKGROUND: We examined the relationship between 10-year predicted atherosclerosis cardiovascular disease (ASCVD) risk score and 25-hydroxyvitamin D in Koreans aged 40-79 years. METHODS: A population-based, cross-sectional design was used from data based on the Korea National Health and Nutrition Examination Survey 2014. RESULTS: A total of 1,134 healthy Koreans aged 40-79 years were included. A positive relationship between serum 25-hydroxyvitamin D level and ASCVD score was shown in women (beta=0.015) after adjusting for central obesity, physical activity, and supplement intake. The chances of being in the moderate to high risk (risk group, ASCVD score >=5%) with vitamin D sufficiency (serum 25 hydroxyvitamin D >=20 ng/mL) was 1.267-fold (95% confidence interval, 1.039 1.595) greater than the chance of being included in the group with vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL) after adjustments in women. CONCLUSION: Our research indicated a significantly positive association between 25-hydroxyvitamin D and ASCVD score. Further detailed studies to evaluate this correlation are needed. PMID- 29788707 TI - Comparison of Fatigue Severity and Quality of Life between Unexplained Fatigue Patients and Explained Fatigue Patients. AB - BACKGROUND: Recently, despite the high prevalence of fatigue in patients, there is a lack of research on the quality of life (QoL) in unexplained fatigue patients, indicating that they are not properly diagnosed and treated. The aim of this study was to compare fatigue severity and QoL between patients with explained and unexplained fatigue. METHODS: The study consisted of 200 Korean adults who complained of fatigue without underlying disease. Fatigue Severity Scale, Short Form Health Survey-36 version 2 (SF-36v2), and Beck Depression Inventory-II (BDI-II) self-questionnaires were administered. Participants were dichotomized to two groups, namely, patients with unexplained or explained fatigue, sorted according to laboratory examination results. The chi-square test, t-test, and Wilcoxon rank-sum test were used, and analysis of covariance was calculated after adjusting for age, sex, body mass index, smoking status, and physical component summary (PCS) of SF-36v2 or BDI-II. RESULTS: PCS of SF-36v2 between the two groups showed significant difference. Compared to patients with explained fatigue, those with unexplained fatigue showed lower physical component scores of QoL. CONCLUSION: QoL of patients with unexplained fatigue could largely diminish than those with explained fatigue. The primary clinician should be aware of poor QoL in patients with unexplained fatigue to identify who is in need of more attention and intervention. PMID- 29788708 TI - Association between Physical Activity and Depressive Mood among Korean Adults with Chronic Diseases. AB - BACKGROUND: This study aimed to investigate the association between physical activity and depressive mood among Korean adults with chronic diseases. METHODS: This study analyzed the 2014 Korean National Health and Nutrition Examination Survey data. The study was restricted to participants aged >=20 years who had completed the survey and were not diagnosed as having depression. After exclusion, 4,676 participants were included in the final analysis. Subjects were categorized according to their level of physical activity. Physical activity was assessed using the International Physical Activity Questionnaire. Patients were categorized into two groups according to depressive traits (normal and depressed) based on the 9-item Patient Health Questionnaire scores. RESULTS: In univariate analysis, significant associations were observed between the level of physical activity and depressive mood in both chronic and healthy groups. Participants with higher levels of physical activity had lower risks of depressive mood than those with lower levels of physical activity, especially patients with chronic diseases (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.31-0.73). Similar trends were observed in multivariate logistic regression analysis (OR, 0.54; 95% CI, 0.34-0.88). CONCLUSION: Physical activity significantly decreased the development of depressive mood among Korean adults with chronic diseases compared with their healthy counterparts. Physical activity must be emphasized in patients with chronic diseases. PMID- 29788709 TI - Influence of Offspring on Self-Rated Health among Older Adults: Evidence from the Korean Longitudinal Study of Aging (2006-2012). AB - BACKGROUND: We investigated whether offspring protect or jeopardize in parents. METHODS: We used data from the Korean Longitudinal Study of Aging and performed a longitudinal analysis of 10,236 individuals at baseline (2006) to estimate the association between offspring-related factors and self-rated health among individuals >=45 years of age. RESULTS: The estimate for self-rated health was 0.612 times lower (95% confidence interval [CI], 0.503-0.746; P<0.0001) for those with zero offspring. The estimate for self-rated health was 0.736 (95% CI, 0.635 0.853; P<0.0001) for those with five offspring or more. The estimate for self rated health was 0.707 (95% CI, 0.528-0.947; P=0.020) for males with zero offspring. The estimate for self-rated health was 0.563 (95% CI, 0.422-0.751; P<0.001) for females with no offspring and for females with five or more offspring. The estimate for self-rated health was 0.686 times lower (95% CI, 0.573-0.822; P<0.0001) for those with five or more offspring compared to females with two offspring. CONCLUSION: Those with more offspring (>=5) and those with no offspring tended to have an increased probability of low self-rated health. Overall, our results suggest that offspring have a significant positive effect on self-rated health, which was evident graphically as an inverted U-shape. PMID- 29788710 TI - Hemiballismus in Uncontrolled Diabetes Mellitus. AB - Hemiballismus, a subtype of chorea, is a rare movement disorder, and is most commonly found secondary to stroke. Movements are involuntary, violent, coarse, and have a wide amplitude. There is increasing report of hemiballismus occurring in non-ketotic hyperglycemia. Spontaneous improvements or remissions were observed in many patients, and treatment should be directed towards the cause of hemiballismus. There is no randomized control trial to guide clinicians in deciding the best treatment option when managing hemiballismus. Symptomatic treatment includes the use of drugs such as dopamine receptor blocker and tetrabenazine. Surgical treatment is reserved for severe, persistent, and disabling hemiballismus. This case is of an elderly woman with long standing uncontrolled diabetes who presented with abnormal movement in her left upper limb for 2 months, which resolved slowly with good control of her glucose levels. Treating physicians need to have a high index of suspicion to prevent mismanagement of the condition. PMID- 29788711 TI - A Rare Case of Renal Impairment Caused by Primary Hypothyroidism. AB - An association between hypothyroidism and renal impairment has rarely been reported in the literature. We describe a case of hypothyroidism that was associated with otherwise unexplained acute kidney impairment, which was reversed with treatment. A 21-year-old female patient presented to her family physician with myalgia, and preliminary investigations revealed an elevated level of creatine kinase and poor renal function. Primary hypothyroidism was diagnosed and no other apparent etiology for renal failure could be identified despite extensive investigations by the Nephrology Department. Notably, the patient's renal impairment showed prompt resolution following thyroid hormone replacement. PMID- 29788712 TI - Correction: Lower Levels of Serum Adiponectin and the T Allele of rs1501299 of the ADIPOQ Gene Are Protective against Polycystic Ovarian Syndrome in Jordan. AB - [This corrects the article on p. 108 in vol. 39.]. PMID- 29788713 TI - Tribochemical Competition within a MoS2/Ti Dry Lubricated Macroscale Contact in Ultrahigh Vacuum: A Time-of-Flight Secondary Ion Mass Spectrometry Investigation. AB - Controlling and predicting the tribological behavior of dry lubricants is a necessity to ensure low friction, long life, and low particle generation. Understanding the tribochemistry of the materials as a function of the environment is of primary interest as synergistic effects exist between the mechanics, the physicochemistry, and the thermodynamics within a contact. However, in most studies the role of the coating internal contaminants in the process is often discarded to the benefit of a more common approach in which the performances of the materials are compared as a function of different atmospheric pressure environments. The study focuses on the understanding of the tribochemical processes occurring between the materials and their internal contaminants inside an AISI440C contact lubricated by a MoS2/Ti coating. Time-of flight secondary ion mass spectrometry is used to study at the molecular level, the material before and after friction. Friction tests with different durations are performed in ultrahigh vacuum at the macroscale to stay relevant to the real application (space). The adsorption/desorption of gaseous species during friction is monitored by mass spectrometry to ensure reliable study of the tribochemical processes inside the contact. The study shows that a competition exists between the Ti- and MoS2-based materials to create the appropriate lubricating materials via (i) recrystallization of MoS2 materials with creation of a MoS xO y material via reactions with internal contaminants (presumably H2O), (ii) reaction of Ti based materials with internal contaminants (mostly H2O and N2). The biphasic material created is highly similar to the one created in both humid air and dry N2 environments and providing low friction and low particle generation. However, the process is incomplete. The study thus brings insight into the possibility of controlling friction via a rational inclusion of reactants in a form of contaminants to control the tribochemical processes governing the low friction and long life. PMID- 29788714 TI - Negative Capacitance beyond Ferroelectric Switches. AB - Negative capacitance transistors are a unique class of switches capable of operation beyond the Boltzmann limit to realize subthermionic switching. To date, the negative capacitance effect has been predominantly attributed to devices employing an unstable insulator with ferroelectric properties, exhibiting a two well energy landscape, in accordance with the Landau theory. The theory and operation of a solid electrolyte field effect transistor (SE-FET) of subthreshold swing less than 60 mV/dec in the absence of a ferroelectric gate dielectric are demonstrated in this work. Unlike ferroelectric FETs that rely on a sudden switching of dipoles to achieve negative capacitance, we demonstrate a distinctive mechanism that relies on the accumulation and dispersion of ions at the interfaces of the oxide, leading to a subthreshold slope (SS) as low as 26 mV/dec in these samples. The frequency of operation of these unscaled devices lies in a few millihertz because at higher or lower frequencies, the ions in the insulator are either too fast or too slow to produce voltage amplification. This is unlike Landau switches, where the SS remains below 60 mV/dec even under quasi static sweep of the gate bias. The proposed FETs show a higher on-current with a thicker oxide in the entire range of gate voltage, clearly distinguishing their scaling laws from those of ferroelectric FETs. Our theory, validated with experiment, demonstrates a new class of devices capable of negative capacitance that opens up alternate methods of steep switching beyond the traditional approach of ferroelectric or memristive FETs. PMID- 29788715 TI - Versatile Electrochemiluminescence Assays for PEDV Antibody Based on Rolling Circle Amplification and Ru-DNA Nanotags. AB - The sensitive and accurate detection methods for PEDV antibody have practical significance for the prevention and treatment of PEDV. In this work, a new multiple pathways signal amplification method was proposed to construct a sensitive electrochemiluminescence (ECL) platform for the detection of PEDV antibody. Using Au NP-modified graphene nanosheet (Au-GN) as the substrate, antibody-antigen reaction as the recognition unit, rolling circle amplification (RCA) for signal enhancement, and assembled cascade Ru-DNA nanotags as signal label, the proposed platform behaved with good specificity and sensitivity. The binding system of biotin-streptavidin, RCA, and Ru(bpy)32+-doped silica nanoparticles (Ru SNPs) showed remarkable amplification efficiency, low background signal, and little nonspecific adsorption. Moreover, the proposed ECL sensor exhibited good analytical performance for PEDV antibody with a wide linear range from 0.1 pg mL-1 to 5000 pg mL-1 with a detection limit of 0.05 pg mL-1 ( S/ N = 3). The proposed strategy exhibited the advantages of excellent stability and sensitivity for determination of the PEDV antibody, which was easy to prepare and had a good application prospect. PMID- 29788716 TI - Porous Silsesquioxane-Imine Frameworks as Highly Efficient Adsorbents for Cooperative Iodine Capture. AB - The efficient capture and storage of radioactive iodine (129I or 131I), which can be formed during nuclear energy generation or nuclear waste storage, is of paramount importance. Herein, we present highly efficient aerogels for reversible iodine capture, namely, porous silsesquioxane-imine frameworks (PSIFs), constructed by condensation of octa(3-aminopropyl)silsesquioxane cage compound and selected multitopic aldehydes. The resulting PSIFs are permanently porous (Brunauer-Emmet-Teller surface areas up to 574 m2/g), thermally stable, and present a combination of micro-, meso-, and macropores in their structures. The presence of a large number of imine functional groups in combination with silsesquioxane cores results in extremely high I2 affinity with uptake capacities up to 485 wt %, which is the highest reported to date. Porous properties can be controlled by the strut length and rigidity of linkers. In addition, PSIF-1a could be recycled at least four times while maintaining 94% I2 uptake capacity. Kinetic studies of I2 desorption show two strong binding sites with apparent activation energies of 77.0 and 89.0 kJ/mol. These energies are considerably higher than the enthalpy of sublimation of bulk I2. PMID- 29788717 TI - Exploiting Crystallographic Regioselectivity To Engineer Asymmetric Three Component Colloidal Nanoparticle Isomers Using Partial Cation Exchange Reactions. AB - The precise placement of different materials in specific regions of a nanocrystal is important for many applications, but this remains difficult to achieve synthetically. Here we show that regioselectivity during partial cation exchange reactions of metal chalcogenide nanocrystals emerges from crystallographic relationships between the precursor and product phases. By maximizing the formation of low-strain interfaces, it is possible to rationally integrate three distinct materials within uniform spherical and rod-shaped colloidal nanoparticles to produce complex asymmetric heterostructured isomers. Through sequential partial exchange of Cu+ in Cu1.8S nanocrystals with Zn2+ and Cd2+, five distinct ZnS/CdS/Cu1.8S nanosphere and nanorod isomers are accessible. PMID- 29788719 TI - Stereocontrolled Synthesis of 3-Sulfonyl Chroman-4-ols. AB - The stereocontrolled reduction of 3-sulfonyl chromen-4-ones by two synthetic methods, NaBH4/LiCl and Pd/C/H2, provides two kinds of 3-sulfonyl chroman-4-ols with three contiguous chiral centers under different reaction conditions. The use of various reaction conditions is investigated for efficient transformation. PMID- 29788718 TI - Morphology and Physical Properties of Hydrophilic-Polymer-Modified Lipids in Supported Lipid Bilayers. AB - Lipid molecules such as glycolipids that are modified with hydrophilic biopolymers participate in the biochemical reactions occurring on cell membranes. Their functions and efficiency are determined by the formation of microdomains and their physical properties. We investigated the morphology and properties of domains induced by the hydrophilic-polymer-modified lipid applying a polyethylene glycol (PEG)-modified lipid as a model modified lipid. We formed supported lipid bilayers (SLBs) using a 0-10 mol % range of PEG-modified lipid concentration ( CPEG). We studied their morphology and fluidity by fluorescence microscopy, the fluorescence recovery after photobleaching method, and atomic force microscopy (AFM). Fluorescence images showed that domains rich in the PEG-modified lipid appeared and SLB fluidity decreased when CPEG >= 5%. AFM topographies showed that clusters of the PEG-modified lipid appeared prior to domain formation and the PEG lipid-rich domains were observed as depressions. Frequency-modulation AFM revealed a force-dependent appearance of the PEG-lipid-rich domain. PMID- 29788720 TI - Transition Metal Oxides as Electrocatalysts for the Oxygen Evolution Reaction in Alkaline Solutions: An Application-Inspired Renaissance. AB - Water splitting is the essential chemical reaction to enable the storage of intermittent energies such as solar and wind in the form of hydrogen fuel. The oxygen evolution reaction (OER) is often considered as the bottleneck in water splitting. Though metal oxides had been reported as OER electrocatalysts more than half a century ago, the recent interest in renewable energy storage has spurred a renaissance of the studies of transition metal oxides as Earth-abundant and nonprecious OER catalysts. This Perspective presents major progress in several key areas of the field such as theoretical understanding, activity trend, in situ and operando characterization, active site determination, and novel materials. A personal overview of the past achievements and future challenges is also provided. PMID- 29788721 TI - Vanishing Thermal Conductance of Carbon Nanotube upon Encapsulation by Zigzag Sulfur Chain. AB - We report an unprecedented enhancement of thermoelectric properties of a single walled carbon nanotube upon encapsulation of a zigzag sulfur chain inside the nanocore. Our calculations on a 70 A long [5, 5] carbon nanotube reveal that the encapsulation of zigzag sulfur chain will lead to a 107% increase in the thermoelectric figure of merit and concomitant quenching of thermal conductance by 90%. We have noticed that finite transmission gradient at the Fermi level combined with destructive quantum interference at the sulfur sites and structural conformation-dependent scattering-induced damping of phonon transmission are attributed to the dramatic improvement of thermoelectric behavior of this material. This finding indeed will help circumvent the long-standing problem in the fabrication of carbon-nanotube-based ultrafast device. PMID- 29788723 TI - Biomineralization of osteoblasts on DLC coated surfaces for bone implants. AB - Diamond like carbon (DLC) films were deposited onto Ti6Al4V and Si wafer substrates by RF plasma enhanced chemical vapor deposition. The influence of dopants such as fluorine (F), silicon (Si), and nitrogen (N) on composition, structure, and biocompatibility was investigated. Ion scattering spectroscopy analysis revealed the presence of dopant atoms in the outer-most layers of the films. Raman studies showed that the position of the G-band shifts to higher frequencies with the fluorine and nitrogen content in the DLC film, whereas the incorporation of Si into DLC induces a decrease of the position of the G peak. The corrosion behavior was studied in simulated body fluid. A higher charge transfer resistance (Rct) was observed for the doped DLC films. The indirect cytotoxicity was performed using L929 fibroblast cells. The coated surfaces were hemocompatible when tested with red blood cells. DLC films were noncytotoxic to L929 cells over a 24 h exposure. Saos-2 osteoblast cell response to the doped and undoped DLC coated surfaces was studied in adhesion, proliferation, differentiation, and mineralization assays. The production of calcium and phosphate by cells on doped DLC, particularly, nitrogen doped DLC, was higher than that on undoped DLC. PMID- 29788724 TI - miR-506 suppresses cervical cancer cell proliferation both in vitro and in vivo. AB - Cervical cancer (CC) is one of the most common gynecological malignancies in women worldwide. Recently increasing evidences indicate aberrant expression of miR-506 was reported to be associated with a variety of tumors. The aimof this study was to evaluate the potential role of miR-506 in CC and verify its effect on the regulation of ABCC4. The expression of miR-506 in cervical cancer tissues and HeLa and C33A cell lines was examined using quantitative Real-time PCR. MTT assay and animals studies were use to examine the effects of miR-506 on cervical cancer proliferation. Luciferase reporter and western blot were used to confirm miR-506 could regulate ABCC4. We found that miR-506 was significantly downregulated in human CC cell lines (HeLa and C33A) and clinical CC specimens as compared with matched cell lines and adjacent normal tissues, while the expression level of ABCC4 was higher in tumor tissues than it in adjacent normal tissues. We also revealed that up-regulated expression of miR-506 could inhibit CC cells proliferation both in vitro and in vivo. Moreover, ABCC4 was identified as a direct target of miR-506 and the inverse relationship between them was also observed. In summary, our finding suggests that miR-506 acts an important role in suppressing CC cell proliferation and suppresses the expression of ABCC4 by directly targeting its 3'-UTR. miR-506 may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in CC, but the role of the miR-506/ABCC4 axis in CC progression needs further study. PMID- 29788725 TI - Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria-dependent apoptosis in lung cancer cells. AB - Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese herb Chuanxiong. Several studies have shown its anti-cancer properties. However, its functions in lung cancer and the underlying cellular mechanisms are relatively unknown. Our present study aimed to investigate the effects of TMPZ on A549 and 95D cells. The MTT assay showed that TMPZ decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that TMPZ strongly suppressed colony formation ability in A549 and 95D cells. Flow cytometric analysis revealed that TMPZ induced S phase arrest in lung cancer cells. In addition, TMPZ induced apoptosis, as shown by the results of propidium iodide/Annexin V double-staining. Furthermore, TMPZ decreased mitochondrial membrane potential (?Psim) in a dose-dependent manner. Finally, western blot analysis of TMPZ-treated cells revealed the activation of Caspase-3 and the increase of the ratio of Bax/Bcl-2. These results demonstrated that TMPZ could suppress carcinogenesis of lung cancer cells through blocking cell cycle and inducing mitochondria-dependent apoptosis by regulating Caspase-3 and Bax/Bcl-2, suggesting that TMPZ may be a promising drug to treat lung cancer. PMID- 29788726 TI - Dynamics of High Risk Clinical Target Volume reduction during Brachytherapy and impact on its coverage in patients with inoperable cervical cancer. AB - Cervical cancer is the third most common cancer in women worldwide. Standard of care for patients with node positive or locally advanced tumors >4 cm is definitive radiotherapy and concurrent chemotherapy. Brachytherapy is an integral part of definitive radiotherapy for cervical cancer. The aim of the study was to show a dynamics of High Risk Clinical Target Volume (HR-CTV) reduction during Brachytherapy (BT) as a part of definitive treatment (External Beam Radiotherapy /EBRT/ +/- Chemotherapy /ChT/) depending on the initial Gross Tumor Volume (GTV) and its impact on HR-CTV coverage in patients with inoperable cervical cancer. We analyzed the dosimetric data for BT of 54 patients who have had Three Dimensional Planning of BT (3D BT). The Gross Tumor Volume, HR-CTV and organs at risk (OARs) were contoured on the magnetic resonance imaging (MRI), subsequently on the co registered MRI images with computed tomography (CT). Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images. Patients were categorized on the basis of whether the 100% isodose line of the point-A prescription dose encompassed the HR-CTV (1st group) or not (2nd group). The 30cc volume has been determined as a cut-off value, which represented the most acceptable value of intermediate size of volumes. The initial mean value of GTV was 42cc. After completion of EBRT/ChT, the mean GTV was 3.24cc what was 91% reduction rate in relation to the initial value. We followed the dynamics of HR CTV reduction during BT and have noted its minimal reduction from 24.3cc (mean value) at the time of the first fraction to the 24.1cc before fourth fraction. The mean V100 was 98% and increased with decreasing of the volume size (p=0.0063, Fisher's exact test). D90 (mean value was 96.3 Gy10) has been correlated with V100 and also, it increased with decreasing of the volume size (p=0.0003). The mean D0.1cc and D2cc of rectum doses were 80 Gy3 and 65.6 Gy3, respectively. The mean ICRU rectal dose for all patients was 67.2 Gy3. The mean D0.1cc (99.5 Gy3), D2cc (79.5 Gy3) and ICRU (75.2 Gy3) of bladder doses were acceptable. Dynamics of HR-CTV reduction during BT was minimal, although, significant reduction of the GTV was achieved after EBRT/ChT. This study revealed that the dose prescription of 7 Gy * 4 fractions to point A was not sufficient indicator for dose coverage of the HR-CTV. However, dosimetric parameters as V100 and D90 were strong indicators for coverage of HR-CTV which was inversely related to the volume of the target and the extension of tumor. However, dosimetric parameters for rectum and bladder (D0.1cc, D2cc and ICRU) did not show dependence on the target volumes. PMID- 29788727 TI - Human Cytomegalovirus (HCMV) infection was not correlated with overall survival in glioblastomas. AB - There were many arguments about the presence of HCMV (Human Cytomegalovirus) in malignant gliomas. This study was to investigate the presence and prognostic value of HCMV in glioblastomas. 68 patients including 64 primary glioblastomas and 4 secondary glioblastomas were involved in this study. Immunofluorescence was adopted for detecting glycoprotein B (gB) and glycoprotein H (gH) of HCMV's in glioblastoma tissues. Kaplan-Meier Analysis and Chi Square were used to evaluate patients' survival and the association between HCMV infection and patients' characteristics respectively. We found that the presence rate of gB and gH were 48.5% (33/68) and 42.6% (29/68) in glioblastomas respectively. The co-occurrence of gB and gH was 30.8%, and the presence rates of either gB or gH in glioblastomas was 60.3%. While IDH R132H mutations were significantly correlated with a better clinical outcome (p=0.006), the presence of neither gB (p=0.551) nor gH (p=0.871) had prognostic values. Furthermore, there was no significant association between the presence of HCMV and gliomas' characteristics, neither with patients' age, gender, KPS, IDH mutations nor PTEN loss. In conclusion, our results supported the fact that HCMV was detected in glioblastomas. However, no predictive value of HCMV was observed, the treatment of glioblastomas targeting HCMV was needed to be revalued by studied again. PMID- 29788728 TI - Clinical characteristics and treatments of patients with alpha-fetoprotein producing gastric carcinoma. AB - Alpha-fetoprotein (AFP) is a well-known tumor marker of hepatic carcinoma and yolk sac tumor. Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare type of gastric cancer with high malignancy and poor prognosis, which make it different from other types of gastric cancer. This rare gastric cancer patient subgroup is likely frequently misdiagnosed which may be related to lack of knowledge of the disease. The purpose of this article is to summarize the mechanism of AFP positive gastric cancer, classification, biological behavior and treatment, in order to assist clinical practitioners to detect AFPGC earlier and treat it better. Previous studies have showed that AFPGC has a complex pathophysiology mechanism. AFPGC is more aggressive and characterized by stronger proliferation, neovascularization, lymphatic invasion and distant metastasis. Furthermore, so far there has been no standard treatment for patients with AFPGC. Nevertheless, our present study summarizes some effective treatments based on previous research outcome. In conclusion, the present study demonstrates that the importance of detecting AFP routinely in serum and tissues in gastric cancer cases, which will greatly improve the diagnosis rate of AFPGC, and in regards to treatment, surgery, chemotherapy, targeted therapy and interventional treatment may have positive impacts on AFPGC treatment outcome. However, further study with a larger sample is required to confirm the reliability and validity of these methods. PMID- 29788729 TI - Three novel microRNAs based on microRNA signatures for gastric mucosa-associated lymphoid tissue lymphoma. AB - This study aimed to identify novel microRNAs (miRNAs) that play crucial regulatory roles in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma by retrieving and analyzing the miRNA expression profile GSE23877. Differentially expressed miRNAs between gastric MALT lymphoma samples and human tonsil tissue samples as well as their target genes were identified. The transcriptional regulatory relationships between miRNAs and target genes were analyzed, and the regulatory network between them was constructed. Target genes annotated as transcription factors (TFs) were screened, and an miRNA-target gene regulatory network was established. Moreover, the expression levels of miRNAs and target genes as well as the correlation between them were verified. In total, 53 upregulated and 25 downregulated miRNAs were obtained, for which 35 and 25 experimentally validated miRNA-target interactions, respectively, were screened. Some miRNAs were significantly enriched in certain pathways; for example, miR 320a was enriched in systemic lupus erythematosus and ribosome, miR-622 in the p53 signaling pathway and chronic myeloid leukemia, and miR-429 in cancer-related pathways. In addition, upregulated miRNAs, including miR-320a, miR-940, and miR 622, and downregulated miRNAs, including miR-331-3p and miR-429, were hub nodes in the miRNA-target gene regulatory network, and the TF MYC was a co-target of miR-320a, miR-622, and miR-429. The expression trends of miR-320a and miR-429 as well as of some of their target genes were consistent with those in the results of microarray analysis. In conclusion, miR-320a, miR-622, and miR-429 are possibly novel miRNAs participating in the pathomechanism of gastric MALT lymphoma. PMID- 29788730 TI - AFP role in predicting recurrence of hepatocellular carcinoma after living donor liver transplantation in HCV patients. AB - HCC is one of the leading causes of death worldwide. Liver transplantation including living donor transplantation is the best available treatment. We have analyzed our experience with LDLT in patients with HCC and HCV in order to determine if alpha feto-protein (AFP) is a better predictor of recurrence than the tumor burden. We have identified all patients with HCV related liver disease and HCC who have undergone LDLT in one center during the period from December 2000 to December 2014. Outcomes from the prospective database were compared for patients who met Milan criteria (single tumor <=5 cm, maximum of 3 total tumors with none >3 cm) or not. Uni- and multi-variable analyses of factors influencing recurrence free survival (RFS) were performed. A total of 142 patients with HCC and HCV associated liver disease underwent LDTL during the study period. RFS was 96.4% at 1 years, 91.8% at 3 years and 91.8% at 5 years. Gender, model for End Stage Liver disease (MELD), pre-transplant therapy, AFP level, tumor number, total tumor size were predictors of recurrence on univariable analysis. On multivariable analysis MELD score (Hazard ratio (HR) 1.16) and Log10 AFP (HR 3.14) were predictors of RFS. In the ROC curve analysis with an AUC of 0.76 the optimal cut-off value of AFP was 26ng/mL. In conclusion MELD score and pre transplant AFP predict recurrence after LDLT for HCC with HCV infection. PMID- 29788731 TI - Claudin-7 (CLDN7) is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, invasion and maintains mesenchymal state. AB - Gastric cancer (GC) ranks as the fourth most common cancer worldwide and is among the most aggressive types of cancer. Claudin-7 (CLDN7) has been found to be aberrantly expressed in some types of cancers. However, the expression and role of CLDN7 on gastric cancer (GC) remain largely unknown. In this study, we have performed the largest expression analysis study to date of CLDN7 in 113 pairs of human GC tissues and non-tumorous adjacent tissues. We found CLDN7 expression is significantly elevated in GC tissues, and the overexpression of CLDN7 is closely related to lymph node metastasis. Furthermore, we observed that CLDN7 executes an oncogenic function, promoting cancer cell proliferation, invasion, and epithelial mesenchymal transition in GC. Given this oncogenic role of CLDN7 in GC formation and progression, CLDN7 may have an indispensable potential for future anti metastatic and therapeutic applications. PMID- 29788732 TI - The current application of ACOSOG Z0011 trial results: Is further implementation of sentinel lymph node intra-operative histopathological examination mandatory in breast cancer patients - a single-centre analysis. AB - The main objective of the ACOSOG Z0011 trial was to determine the impact of abandoning complete axillary lymph node dissection (ALND) on survival of breast cancer patients with sentinel node lymph (SLN) metastasis in whom breast conserving therapy (BCT) had been performed. The aim of our study was to assess the clinical value of intra-operative histopathological examination of SLN. Our study comprised 1284 invasive breast cancer patients in whom sentinel lymph node biopsy (SLNB) was carried out. SLN intra-operative histopathological assessment was routinely performed in patients treated within the first period (07.2013 06.2014). However, the decision regarding intra-operative assessment was made by the surgeon for the patients who underwent this evaluation in the later period 07.2014-06.2015 and were submitted for BCT. BCT was performed in 72.4% of patients. In total, 316 patients (24.6%) developed SLN-metastasis. Within the period 07.2014-06.2015, SLN intra-operative microscopic evaluation was performed in 20.8% of patients submitted for BCT. ALND was omitted in 27.5% of patients demonstrating SLN metastasis, in comparison with 15.5% of the group from the previous period (p=0.0094). The proportion of patients demonstrating macrometastasis in SLN who received conservative treatment to the axilla increased from 5.4% to 23.1% (p=0.0007). The choice of SLN final histopathological assessment may allow for deferral of decision on more extensive surgery of the axilla in patients submitted for SLNB. The omission of routinely performed SLN intra-operative histopathological evaluation has led to a statistically significant increase in the proportion of patients in whom complete ALND was avoided. PMID- 29788733 TI - Sulindac induces differentiation of glioblastoma stem cells making them more sensitive to oxidative stress. AB - Glioblastoma tumors (GBM) are very heterogeneous, being comprised of several cell subtypes, including glioblastoma stem cells (GSC). These tumors have a high rate of recurrence after initial treatment and one of the most prevalent theories to explain this is the cancer stem cell theory, which proposes that glioblastomas arise from mutations that transform normal neural stem cells (NSC) into GSC, which are highly resistant to oxidative stress and anti-cancer therapies. Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has been shown to protect the normal cells against oxidative damage by initiating a preconditioning response, but selectively sensitizes several cancer cell lines to agents that affect mitochondrial respiration, resulting in enhanced killing of the cancer cells. These effects of sulindac are independent of its NSAID activity. There is little information on the effect of sulindac on normal and cancer stem cells. To study the effect of sulindac on both normal and cancer stem cells, we have isolated normal neural stem cells (NSC), from mice hippocampi and glioblastoma stem cells (GSC) from a glioma cell line, U87. As expected from previous studies sulindac can protect normal astrocytes against oxidative stress. Sulindac induces differentiation of both NSC and GSC cells and sulindac upregulates neurogenesis in NSC. The differentiated NSC are also protected from oxidative stress damage, whereas the differentiation of GSC by sulindac increases the sensitivity of these cells to agents that cause oxidative stress. The S epimer of sulindac is more effective than the R epimer in inducing neuronal differentiation in both NSC and GSC. These results indicate that the ability of sulindac to induce GSC differentiation may have therapeutic value in preventing tumour recurrence. PMID- 29788734 TI - Neovascularization in Ewing's sarcoma. AB - Ewing's sarcoma is the second most common bone malignancy in adolescents and young adults after osteosarcoma. Similar to other solid tumors, Ewing's sarcomas require an adequate vascular supply to grow and survive. The development and maintenance of vascular supply is accomplished via three main mechanisms; angiogenesis, vasculogenesis, and tumor cell vasculogenic mimicry. In addition, growth factors, parallel biochemical pathways and the tumor microenvironment are implicated in the initiation and maintenance of neovascularization. This article summarizes the different mechanisms and factors that contribute to neovascularization in Ewing's sarcoma, and discusses the significance of this phenomenon for current treatment options. PMID- 29788735 TI - HPV status and its genomic integration affect survival of patients with cervical cancer. AB - To evaluate the relapse-free and overall survival of HPV-positive patients with regard to the physical status of type 16 HPV and of HPV-negative patients with primary CC. As a main result of the study the predictive value of the physical status of type 16 HPV was determined for relapse-free and overall survival of patients with CC. Episomal form of the virus is a favorable predictive factor. Integrated form of the virus is a severely unfavorable predictive factor and survival of such patients is significantly lower, than for HPV- patients and patients with mixed form of the virus. The results of the research are data on survival of patients with CC depending on the physical status of the virus (for HPV+ patients) and of patients with HPV-negative cancer. PMID- 29788736 TI - Evaluation of overall survival rate of different therapies in the treatment of T1 T3 prostate cancer: a network meta-analysis. AB - We performed this network meta-analysis (NMA) in order to compare the overall survival rate of six different therapies of T1-T3 prostate cancer (PC). The therapies include radiotherapy (RT), endocrine therapy (ET), Cryoablation (CRYO), radical prostatectomy (RP), RT+ET and RP+ET. Pubmed, Embase, Cochrane Library, Google Scholar, Web of Science and MEDLINE were searched to collect relevant literature from the inception of the study till February 2017. Cohort studies meeting the inclusion criteria were included in the study. A combination of direct and indirect evidence was performed to evaluate the odds ratio (OR) and draw surface under the cumulative ranking curves (SUCRA). Nine eligible cohort studies were included in this NMA, including 20,644 patients suffering from T1-T3 PC. The pairwise meta-analysis revealed that compared with the ET regimen, the RP and RP+ET regimens exhibited comparatively higher overall survival rates (OR = 2.81, 95%CI = 2.09 ~ 3.78; OR = 3.15,95%CI = 1.80 ~ 5.50, respectively). The results of SUCRA values demonstrated that the RP + ET regimen occupied the first place (89.5%) in terms of overall survival rate, and the RP regimen came second (84.83%). Thus, the RP+ET regimen had better efficacy in the treatment of T1-T3 PC in combined-therapeutic regimens, and the RP regimen presented better efficacy in mono-therapeutic regimen. Our findings indicate that the RP+ET regimen had better efficacy on improving the overall survival rate of T1-T3 PC patients, and the RP regimen ranked second. PMID- 29788737 TI - Diagnosis for carcinoma of unknown primary site with the aid of simple PCR tests: a single-center experience. AB - This study was aimed to incorporate PCR testing in the determination of organ/tissue origin for cancers of unknown primary site (CUP). We developed a PCR panel consisting of 7 expression markers (CDX2, CDH17, SPB, UGRP, MAM, LPB, TG) and 2 genes frequently mutated in cancer (KRAS and BRAF). The expression tests were intentionally interpreted in a non-quantitative way, i.e. classified tumors either as positive or negative expressors. While applying these tests to 135 cancers belonging to 8 common types of adenocarcinomas (AdCa), we observed that this panel was capable to clearly discriminate between gastrointestinal vs. female reproductive tract vs. lung vs. thyroid tumors in 112 (83%) of cases and provided suggestive clues to correct diagnosis in 20 (15%) of instances. We further assessed the performance of this panel, coupled with the occasional use of 2 additional mutation tests (somatic: EGFR; germ-line: BRCA1), in the real diagnostic setting. The PCR analysis of 20 consecutive CUP with known IHC status turned out to be clinically useful in 19 (95%) cases, with 16 (80%) instances of resolving the existing controversy and 3 (15%) cases of providing valuable confirmation to suspected diagnosis. PCR testing of 20 consecutive CUP with unknown IHC status succeeded to establish tumor organ/tissue origin in 15 (75%) instances and provided suggestive clues to the diagnosis in 3 (15%) patients. We conclude that simple non-expensive laboratory-developed PCR assays may aid CUP diagnosis in a significant proportion of cases. PMID- 29788738 TI - Hashimoto's thyroiditis, nodular goiter or follicular adenoma combined with papillary thyroid carcinoma play protective role in patients. AB - Papillary thyroid carcinoma (PTC) is often combined with other types of thyroid disease, such as Hashimoto's thyroiditis(HT), nodular goiter(NG), Follicular adenoma(FA) and other types. However, the function of these diseases in PTC tumorigenesis and development is not well understood. In this research, 563 PTC patients were recruited and divided into two groups according to pathological diagnosis, namely simple PTC (PTC) and PTC combined with other thyroid diseases (PTC+). Clinicopathological characteristics and BRAFV600E mutation status were compared between PTC and PTC+. Our data showed that there was a statistically significant difference in gender (P=0.007), tumor diameter (5mm, P=0.012; 1cm, P=0.042), lymph node metastasis (P=0.000) and BRAFV600E mutation status (P=0.001) between PTC and PTC+. PTC+ patients have lower lymph node metastasis rate, even if PTC nodule diameter is larger than 5mm (P=0.005) or >=1cm (P=0.049) or BRAFV600E is mutated (P=0.001). In conclusion, our study suggests that HT, NG and FA, are protective factors of PTC patients, and PTC+ patients have lower lymph node metastasis and BRAFV600E mutation rate compared with simple PTC patients. PMID- 29788739 TI - Identification of recurrent risk-related genes and establishment of support vector machine prediction model for gastric cancer. AB - This study sought to investigate genes related to recurrent risk and establish a support vector machine (SVM) classifier for prediction of recurrent risk in gastric cancer (GC).Based on the gene expression profiling dataset GSE26253, feature genes that were significantly associated with survival time and status were screened out. Subsequently, protein-protein interaction (PPI) network was constructed for these feature genes, and genes in this network was optimized using betweenness centrality algorithm in order to identify genes potentially correlated with GC (named as GCGs). In total, 1202 feature genes were identified to be significantly associated with survival time and status of GC, among of which, 65 genes were identified as a classifier that was able to recognize recurrence and nonrecurrence GC cases with a high sensitivity and specificity, predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC). Furthermore, the classifier was able to reasonably classify tumor samples in GSE15459 into high and low recurrent risk groups. Among those genes, a set of genes were predicted to have interactions (e.g. RHOA interacting with TGFBR1, PRKACA and PLCG1; TGFBR1 interacting with TGFBR2) and be involved in pathways like MAPK signaling (e.g. TGFBR1 and TGFBR2), adherens junction (e.g. RHOA) and apoptosis (e.g. PRKACA).The genes in the classifier model may be related to GC recurrence, and the classifier model may contribute to the prediction of recurrent risk in GC. PMID- 29788740 TI - Multiparametric MRI analysis of morphologico-functional features of DCIS - correlation with grade of nuclear atypia. AB - The aim was to analyze morphologico-functional characteristics of ductal carcinoma in situ (DCIS) in breast MRI to assess signs correlating with the degree of nuclear atypia. From 636 malignant lesions, 114 were DCIS (17.92%): 44 cases of high-grade (38.60%), 37 intermediate (32.45%), 33 low-grade (28.95%). MRI characteristics - T2 signal intensity (SI), shape, margins, contrast enhancement, peripheral/ductal enhancement, kinetic curve, presence of restriction of diffusion were correlated with the nuclear grade of DCIS. Statistical analysis was performed, statistical significance and Odds ratio (OR) were calculated. Signs of high-grade lesions were low SI in T2w (p=0.042), nonhomogeneous contrast enhancement (p=0.012), wash-out phenomenon (p=0.04), high SI in diffusion weighted imaging (DWI) (p<0.0001), restriction of diffusion in apparent diffusion coefficient map (p<0.0001). DWI and wash-out phenomenon reached the highest OR (56.00, 9.76). Breast MRI using DWI and multiparametric analysis provides important information about the degree of nuclear atypia. PMID- 29788741 TI - FOXA1 and CK7 expression in esophageal squamous cell carcinoma and its prognostic significance. AB - Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common malignant tumors in human. Some ESCC cells express adenocarcinoma cell markers, such as Cytokeratin 7 (CK7), but the clinical significance of these cells in ESCC is unknown. Immunohistochemical analysis of CK7 and Fork head box protein A1(FOXA1, an upstream regulator of CK7) was performed on 610 ESCC specimens using tissue microarray. In total, positive staining of CK7 was 59/594 (10%). CK7 expression was correlated with ESCC differentiation (P=0.006). The expression of CK7 is associated with poor overall survival (OS) of ESCC patients (P=0.0498). FOXA1 positive staining was 180/586(31%). FOXA1 expression correlates with differentiation (P<0.0001) and vascular invasion status (P=0.016) of ESCC. FOXA1 expression was non-independently correlated with poor prognosis of OS in ESCC patients (P=0.1198), but correlated with the prognosis of ESCC patients in some specific pathological characteristics, such as age less than 61 years (P=0.0066), tumor located in the middle segment of esophagus (P=0.0046), and non-lymph node metastasis (P=0.0377). Correlation analysis between the CK7 and FOXA1 expression was positive (P<0.0001). In conclusion, FOXA1 expression was positive correlated with CK7 expression. CK7 expression is an independent prognostic factor for ESCC, and FOXA1 is a non-independent prognostic factor. CK7 and its upstream factor FOXA1 both can be used as potential targets for ESCC therapy. PMID- 29788742 TI - miR-483 is down-regulated in gastric cancer and suppresses cell proliferation, invasion and protein O-GlcNAcylation by targeting OGT. AB - MicroRNAs (miRNAs) are involved in the gastric carcinogenesis and progression. Here, we confirmed that miR-483 was frequently decreased in gastric cancer patients. The expression levels of miR-483 were negatively correlated with tumor stage, node metastasis and stromal invasion. Log-rank tests demonstrated that low expression of miR-483 was strongly correlated with poor overall survival in patients with gastric cancer. Moreover, ectopic expression of miR-483 remarkably suppressed gastric cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of gastric cancer cells, while low expression of miR-483 exhibited the opposite effect. Bioinformatics analysis revealed that OGT was a potential target of miR-483, and miR-483 inhibited the expression level of OGT mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-483 was negatively correlated with OGT in gastric cancer tissues. In addition, modulation of miR-483 expression could affect the global cellular protein O-GlcNAcylation in gastric cancer cells. Furthermore, silencing of OGT counteracted the effects of miR-483 repression, while its overexpression reversed tumor inhibitory effects of miR-483. In conclusion, our study revealed that miR-483 functions as a tumor suppressor by inhibiting proliferation, invasion and protein O-GlcNAcylation of gastric cancer via targeting OGT, and that miR-483 may serve as prognostic or therapeutic target for gastric cancer. PMID- 29788743 TI - Novel insights into transcriptional dysregulation in colorectal cancer. AB - Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Although CRC has been comprehensively characterized at the molecular level, the tumor heterogeneity hinders the identification of reliable diagnostic, prognostic and predictive biomarkers. Molecular stratification of CRC is based on prevalent gene mutations and transcription profiles but its significance for clinical practice remains obscure. Indeed, activating mutations in the genes KRAS, NRAS and BRAF are the only predictive biomarkers for anti-EGFR antibody therapy routinely tested the clinic for advanced stages of CRC. Gene expression signatures are important for clarifying the molecular mechanisms of CRC development and progression, but only two such tests for predicting recurrence risk are commercially available. The aim of our study was to propose a diagnostic approach based on mutation and gene expression analysis that can be routinely applied in the clinic for defining the most appropriate treatment strategy for each patient. We used qPCR to determine the presence of KRAS mutations and measure the transcription levels of a panel of 26 genes in 24 CRC patients. Statistical analyses were applied to check for associations between clinico pathological and molecular parameters. Our results reveal novel data concerning CRC carcinogenesis: almost universal downregulation of EGFR; differential role of the pro-inflammatory cytokines TNF-alpha and IL-6; overexpression of the vitamin B12 transporter transcobalamin 1; tumor-suppressor function of SETD2, CA7 and GUCA2B. The practical application of these findings has yet to be clarified. PMID- 29788744 TI - General practitioners' participation in cancer treatment in Norway. AB - INTRODUCTION: General practitioners (GPs) participate in a patient's cancer care to different extents at different times, from prevention and diagnosis to treatment and end-of-life care. Traditionally, the GP has had a minor role in cancer treatment. However, oncological and surgical services frequently delegate limited cancer treatment tasks to GPs, especially in rural areas far from hospitals. The aim of this study was to explore the extent of GPs' participation in cancer treatment in Norway. METHODS: This study was an observational questionnaire study. In 2007, the chief municipal medical officer in all 93 municipalities in North Norway and a 25% random sample (85 municipalities) in South Norway was asked to identify up to five GPs who had recently participated in local treatment of cancer patients, and to forward a patient questionnaire to them. RESULTS: Seventy-eight GPs in 49 municipalities returned completed questionnaires for 118 patients, most of them with progressive disease and living in rural areas. All the GPs reported substantial participation in therapeutic tasks for this select group of patients. Not counting palliative treatment, 64% of the GPs participated in cancer treatment either directly, or indirectly through referrals. Twenty patients received chemotherapy; they belonged to no particular diagnostic category. Eighty-eight percent of the GPs prescribed some kind of palliative medicine, such as analgesic, antiemetic, anxiolytic or antidepressant. Morphine was prescribed equally often by GPs and hospitals. Eighty-one percent of GPs reported having had a thorough conversation with the patient about the patient's condition and circumstances. CONCLUSION: In this group of GPs, participation rates were high for most of the therapeutic and communicative tasks suggested in the questionnaire. GP participation is feasible not only in palliative care, but also in some aspects of oncological treatment and in clinical follow-up. Communication with both patient and hospital seemed good in this local setting. GPs are important helpers for some cancer patients. PMID- 29788745 TI - Obesity and physical fitness indices of children aged 5-12 years living on remote and isolated islands. AB - INTRODUCTION: Obesity has become one of the major health risks in childhood, significantly affecting children's health and physical fitness. Although the marked increase of obesity in urban areas is well established, evidence is limited in remote and isolated areas with adverse socioeconomic features. The aim of this study was to examine the prevalence of obesity and its association with physical performance indices in young school-aged children living in 18 remote and isolated Greek islands. METHODS: Four hundred and sixty-three children (244 boys, 219 girls), aged 5-12 years underwent a series of physical fitness tests including 20 m sprint, standing long jump, 1 kg medicine ball throw, agility T test and sit-and-reach test. Age and gender BMI cut-off points were determined according to World Health Organisation (WHO) norms. RESULTS: The prevalence of obesity was 23.8% and 13.2% for boys and girls, respectively. A negative body mass index (BMI) main effect was observed for weight-bearing activities, such as 20 m sprint (F=6.21, p=0.000, η2=0.041) and standing long jump (F=11.369, p=0.000, η2=0.074), while medicine ball throw was positively correlated with BMI in children aged 9-12 years. CONCLUSION: The results of this study confirmed previous findings on obesity prevalence in Greece. A negative association was also found between BMI and physical fitness indices and, in particular, in weight bearing activities. It is critical to establish physical education interventions and physical fitness programs at schools, aiming to increase motivation for physical activity participation. PMID- 29788746 TI - The concept of "harm" in Internet gaming disorder. AB - Internet gaming disorder (IGD) is a proposed condition that refers to persistent gaming leading to clinically significant impairment. However, there have been few attempts to study the different types and degrees of harm caused by IGD. This commentary describes some of the negative intrapersonal and interpersonal effects of an extreme time investment in gaming activities in the context of IGD. Future research should examine the way in which IGD harms may occur at different levels and degrees. This may enhance the screening of individuals whose behavior is suspected to meet the definition of the proposed IGD criteria. PMID- 29788747 TI - Internet pornography viewing preference as a risk factor for adolescent Internet addiction: The moderating role of classroom personality factors. AB - Background and aims Adolescent Internet pornography viewing has been significantly increased in the last decade with research highlighting its association with Internet addiction (IA). However, there is little longitudinal data on this topic, particularly in relation to peer context effects. This study aimed to examine age- and context-related variations in the Internet pornography IA association. Methods A total of 648 adolescents, from 34 classrooms, were assessed at 16 years and then at 18 years to examine the effect of Internet pornography preference on IA in relation to the classroom context. IA was assessed using the Internet Addiction Test (Young, 1998), Internet pornography preference (over other Internet applications) was assessed with a binary (yes/no) question, and classroom introversion and openness to experience (OTE) with the synonymous subscales within the Five Factor Questionnaire (Asendorpf & Van Aken, 2003). Results Three-level hierarchical linear models were calculated. Findings showed that viewing Internet pornography exacerbates the risk of IA over time, while classroom factors, such as the average level of OTE and introversion, differentially moderate this relationship. Discussion and conclusion The study demonstrated that the contribution of Internet pornography preference (as an IA risk factor) might be increased in more extroverted classrooms and decreased in OTE classrooms. PMID- 29788749 TI - University life with ASD: Faculty knowledge and student needs. AB - Increasingly, young adults with autism spectrum disorder are attending 4-year universities. The transition to adulthood can be challenging for these students, and university life poses its own set of demands. The present article takes a mixed-methods approach by including two studies utilizing complementary methodologies. Through in-depth interviews with students with autism spectrum disorder ( n = 13) and college professors ( n = 18), the purpose of the first study was to evaluate the experiences and needs of college students with autism spectrum disorder and identify the knowledge that faculty members possessed about working with these students. Through survey methodology with a larger sample of faculty members ( n = 132), the purpose of the second study was to obtain more information about faculty knowledge of autism spectrum disorder, and to learn whether their pedagogical practices accommodated students with autism spectrum disorder. Findings revealed that autism is often an "invisible" disability on campuses, and there are many things that professors need to know with regard to working with these students in particular. Implications for practice are discussed. PMID- 29788748 TI - The impact of comorbid impulsive/compulsive disorders in problematic Internet use. AB - Background and aims Problematic Internet use (PIU) is commonplace but is not yet recognized as a formal mental disorder. Excessive Internet use could result from other conditions such as gambling disorder. The aim of the study was to assess the impact of impulsive-compulsive comorbidities on the presentation of PIU, defined using Young's Diagnostic Questionnaire. Methods A total of 123 adults aged 18-29 years were recruited using media advertisements, and attended the research center for a detailed psychiatric assessment, including interviews, completion of questionnaires, and neuropsychological testing. Participants were classified into three groups: PIU with no comorbid impulsive/compulsive disorders (n = 18), PIU with one or more comorbid impulsive/compulsive disorders (n = 37), and healthy controls who did not have any mental health diagnoses (n = 67). Differences between the three groups were characterized in terms of demographic, clinical, and cognitive variables. Effect sizes for overall effects of group were also reported. Results The three groups did not significantly differ on age, gender, levels of education, nicotine consumption, or alcohol use (small effect sizes). Quality of life was significantly impaired in PIU irrespective of whether or not individuals had comorbid impulsive/compulsive disorders (large effect size). However, impaired response inhibition and decision-making were only identified in PIU with impulsive/compulsive comorbidities (medium effect sizes). Discussion and conclusions Most people with PIU will have one or more other impulsive/compulsive disorders, but PIU can occur without such comorbidities and still present with impaired quality of life. Response inhibition and decision making appear to be disproportionately impacted in the case of PIU comorbid with other impulsive/compulsive conditions, which may account for some of the inconsistencies in the existing literature. Large scale international collaborations are required to validate PIU and further assess its clinical, cognitive, and biological sequelae. PMID- 29788751 TI - Radiographic analysis of the correlation between ossification of the nuchal ligament and sagittal alignment and segmental stability of the cervical spine in patients with cervical spondylotic myelopathy. AB - Background Ossification of the nuchal ligament (ONL) caused by chronic injury to the nuchal ligament (NL) is very common in instability-related cervical disorders. Purpose To determine possible correlations between ONL, sagittal alignment, and segmental stability of the cervical spine. Material and Methods Seventy-three patients with cervical spondylotic myelopathy (CSM) and ONL (ONL group) and 118 patients with CSM only (control group) were recruited. Radiographic data included the characteristics of ONL, sagittal alignment and segmental stability, and ossification of the posterior longitudinal ligament (OPLL). We performed comparisons in terms of radiographic parameters between the ONL and control groups. The correlations between ONL size, cervical sagittal alignment, and segmental stability were analyzed. Multivariate logistic regression was used to identify the independent risk factors of the development of ONL. Results C2-C7 sagittal vertical axis (SVA), T1 slope (T1S), T1S minus cervical lordosis (T1S-CL) on the lateral plain, angular displacement (AD), and horizontal displacement (HD) on the dynamic radiograph increased significantly in the ONL group compared with the control group. The size of ONL significantly correlated with C2-C7 SVA, T1S, AD, and HD. The incidence of ONL was higher in patients with OPLL and segmental instability. Cervical instability, sagittal malalignment, and OPLL were independent predictors of the development of ONL through multivariate analysis. Conclusion Patients with ONL are more likely to have abnormal sagittal alignment and instability of the cervical spine. Thus, increased awareness and appreciation of this often-overlooked radiographic finding is warranted during diagnosis and treatment of instability-related cervical pathologies and injuries. PMID- 29788750 TI - Exercise motivational regulations and exercise addiction: The mediating role of passion. AB - Background and aims The study explored the mediating role of forms of passion in the relationship between motivational regulations in exercise and exercise addiction (EA). Methods A total of 485 university students (368 males and 117 females; Mage = 20.43, SD = 3.21) completed a questionnaire measuring the frequency and intensity of exercise, motivational regulations in exercise, passion for exercise, and EA. Controlling the effects of age, frequency, and intensity of practice, the relationships between the study variables were examined though a path analysis. Results Both self-determined and non-self determined forms of motivation showed positive association with EA. The forms of motivation with greatest predictive power for EA were introjected and integrated regulations. Both forms of motivation had positive direct and indirect effects through obsessive passion (OP) on EA; however, integrated regulation also showed negative indirect effects through harmonious passion on EA. Conclusions Both forms of passion and, especially, OP, seem to affect how motivational regulations are associated with EA. These findings clarify the association found in previous studies between self-determined forms of motivation and EA. PMID- 29788753 TI - Do gaming disorder and hazardous gaming belong in the ICD-11? Considerations regarding the death of a hospitalized patient that was reported to have occurred while a care provider was gaming. AB - There has been much debate regarding the extent to which different types and patterns of gaming may be considered harmful from individual and public health perspectives. A recent event in which a hospitalized patient was reported to have died while a care provider was gaming is worth considering as an example as to how gaming may distract individuals from work-related tasks or other activities, with potential negative consequences. As the 11th edition of the International Classification of Diseases is being developed, events like these are important to remember when considering entities like, and generating criteria for, disordered or hazardous gaming. PMID- 29788752 TI - Cue-reactivity in behavioral addictions: A meta-analysis and methodological considerations. AB - Background and aims Recent research has applied cue-reactivity paradigms to behavioral addictions. The aim of the current meta-analysis is to systematically analyze the effects of learning-based cue-reactivity in behavioral addictions. Methods The current meta-analysis includes 18 studies (29 data sets, 510 participants) that have used a cue-reactivity paradigm in persons with gambling (eight studies), gaming (nine studies), or buying (one study) disorders. We compared subjective, peripheral physiological, electroencephal, and neural responses toward addiction-relevant cues in patients versus control participants and toward addiction-relevant cues versus control cues in patients. Results Persons with behavioral addictions showed higher cue-reactivity toward addiction relevant cues compared with control participants: subjective cue-reactivity (d = 0.84, p = .01) and peripheral physiological and electroencephal measures of cue reactivity (d = 0.61, p < .01). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, median cingulate cortex, subgenual cingulate, and precentral gyrus. Persons with gambling, gaming, or buying disorders also showed higher cue-reactivity toward addiction-relevant cues compared with control cues: subjective cue-reactivity (d = 0.39, p = .11) and peripheral physiological and electroencephal measures of cue-reactivity (d = 0.47, p = .05). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, angular gyrus, inferior network, and precuneus. Discussion and conclusions Cue-reactivity not only exists in substance-use disorders but also in gambling, gaming, and buying disorders. Future research should differentiate between cue-reactivity in addictive behaviors and cue reactivity in functional excessive behaviors such as passions, hobbies, or professions. PMID- 29788754 TI - Sleep quality as a mediator of problematic smartphone use and clinical health symptoms. AB - Background and aims Although smartphone use brings many benefits for adolescents, it is also associated with many serious health problems. This study examined the relationship between problematic smartphone use (PSU) and clinical health symptoms (e.g., body dysfunction) and the mediating effects of sleep quality on this relationship in adolescents. Methods Participants in this cross-sectional survey were 686 middle- and high-school students (girls = 55.7%, Mage = 12.98 +/- 1.38 years). Participants completed self-report measures of PSU, sleep quality, and physical symptoms. Correlation analyses and structural equation modeling between adolescents' PSU and the variables of interest were conducted. Results This study indicated that there was a significant positive correlation between PSU and health symptoms. Furthermore, sleep quality mediated the relationship between PSU and health symptoms. Discussion and conclusions Findings suggest that to promote health and wellness in adolescents, individuals should be encouraged to place boundaries on smartphone use, especially at bedtime. Reducing adolescents' exposure to smartphone use in this way may hold promise for improving the efficacy of PSU prevention efforts for adolescents. PMID- 29788755 TI - Gaming under the influence: An exploratory study. AB - Background and aims Association between substance use and excessive play of online games exists both in theory and research. However, no study to date examined playing online games under the influence of licit and illicit drugs. Methods We questioned a convenient online sample of 3,952 Czech online gamers on their experiences and motives of using caffeine, alcohol, tobacco, psychoactive pharmaceuticals, and illicit drugs while playing massive multiplayer online games (MMOGs). Results The results showed low prevalence of illicit drug use while playing online games. Substance use was positively associated with intensity of gaming and both addiction and engagement; psychoactive substances with stimulating effect were linked to higher engagement and gaming intensity, whereas use of sedatives was associated with higher addiction score. Substance use varied slightly with the preference of game genre. Discussion Drug use while playing appears as behavior, which is mostly not related to gaming - it concerns mostly caffeine, tobacco, alcohol, or cannabis. For some users, however, drug use was fueled by motivations toward improving their cognitive enhancement and gaming performance. PMID- 29788758 TI - Synthesis and biological evaluation of 2-aminothiazole-thiazolidinone conjugates as potential antitubercular agents. AB - AIM: Mycobacterium tuberculosis, which causes tuberculosis, continues to infect millions of the global population, resulting in 1.8 million deaths worldwide in 2015. METHODOLOGY: Hybrids of 2-amino-4-methylthiazole bearing 5-acetyl/5-ethyl carboxylate functionality with 5-arylidene thiazolidinone moiety (6a-k and 9a-d) were synthesized and screened for antitubercular and antimicrobial activities. RESULTS & DISCUSSION: 5-ethyl carboxylate derivative 6k revealed half antitubercular activity (minimal inhibitory concentration = 1.56 MUg/ml) than the acetyl analog 6c (minimal inhibitory concentration = 0.78 MUg/ml), however, it exhibited more potent broad spectrum antibacterial and antifungal activities in addition to its excellent safety profile with high selectivity toward M. tuberculosis over normal human lung cells. Collectively, these data suggested that compound 6k can be considered as an ideal lead compound for further optimization. PMID- 29788759 TI - Advocating for mutually beneficial access to shelved compounds. PMID- 29788756 TI - Correlates of frequent gambling and gambling-related chasing behaviors in individuals with schizophrenia-spectrum disorders. AB - Background and aims Published research on the relationship between disordered gambling and schizophrenia is limited. However, existing data suggest that individuals with schizophrenia/schizoaffective disorder may have a high prevalence of co-occurring disordered gambling. As such, effective strategies for screening and assessing gambling-related problems in individuals with psychosis are needed. The goal of this study was to explore the correlates of increased gambling frequency and chasing behavior, a hallmark feature of gambling disorder, in a sample of individuals with schizophrenia and schizoaffective disorders. Methods Data from 336 participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder were used to examine differences between non-gamblers, infrequent gamblers, frequent gamblers who do not report chasing, and frequent gamblers who report chasing on a variety of associated features and symptoms of schizophrenia and disordered gambling. Results and discussion The results of the study support the conclusion that chasing behavior in individuals with schizophrenia/schizoaffective disorder lies on a continuum of severity, with more frequent gamblers endorsing greater chasing. Chasing was also associated with indicators of lower functioning across co-occurring disorders, such as greater problems with alcohol and drugs, greater gambling involvement, and a family history of gambling problems. The findings from the study suggest the utility of screening for chasing behavior as a brief and efficient strategy for assessing risk of gambling problems in individuals with psychotic-spectrum disorders. PMID- 29788757 TI - Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction. AB - Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26). Results Expression levels of GluN2A, GluN2D, and GluN3B subunits were not statistically different between game addicts and the control group. However, the mRNA expression of the GluN3A subunit was downregulated in PBLs of game addicts. Discussion and conclusions Transcriptional levels of GluN2A and GluN2D subunits in online computer game addicts are similar to our previously reported data of opioid addiction and are not different from the control group. However, unlike our earlier finding of drug addiction, the mRNA expression levels of GluN3A and GluN3B subunits in PBLs of game addicts are reduced and unchanged, respectively, compared with control subjects. It seems that the downregulated state of the GluN3A subunit of NMDA receptor in online computer game addicts is a finding that deserves more studies in the future to see whether it can serve as a peripheral biomarker in addiction studies, where the researcher wants to rule out the confusing effects of abused drugs. PMID- 29788760 TI - Regression patterns of choroidal melanoma: After palladium-103 (103Pd) plaque brachytherapy. AB - PURPOSE:: To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy. METHODS:: Retrospective interventional case series including 170 consecutive patients treated with 103Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology. RESULTS:: The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2-11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0-7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% ( n = 86/170), amelanotic in 10% ( n = 17/170), and variably pigmented in 39% ( n = 67/170). Tumor pigmentation increased in 64% ( n = 106/166), decreased in 18% ( n = 30/166), and was unchanged in 18% ( n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% ( n = 12/120) had decreased tumor-related vascularity and 90% ( n = 108/120) showed complete resolution. Subretinal fluid was present in 34% ( n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% ( n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% ( n = 91/149) showed increased reflectivity on regression. We noted a crescendo-decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis. CONCLUSION:: Findings related to choroidal melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound. PMID- 29788761 TI - Prevalence of gambling-related harm provides evidence for the prevention paradox. AB - Background The prevention paradox (PP) describes a situation in which a greater number of cases of a disease-state come from low-risk members of a population, because they are more prevalent than high-risk members. Past research has provided only tangential and disputed evidence to support the application of the PP to gambling-related harm. Aims To assess whether the PP applies to gambling, the prevalence of a large set (72) of diverse harmful consequences from gambling was examined across four risk categories for problem gambling, including no-risk, low-risk, moderate-risk, and problem-gambling. Methods Respondents who had gambled on non-lottery forms in the past 6 months completed an online survey (N = 1,524, 49.4% male). The data were weighted to the known prevalence of gambling problems in the Victorian community. Results The prevalence of gambling harms, including severe harms, was generally higher in the combined categories of lower risk categories compared to the high-risk problem-gambling category. There were some notable exceptions, however, for some severe and rare harms. Nevertheless, the majority of harms in the 72-item list, including serious harms such as needing temporary accommodation, emergency welfare assistance, experiencing separation or end of a relationship, loss of a job, needing to sell personal items, and experiencing domestic violence from gambling, were more commonly associated with lower risk gamblers. Conclusion Many significant harms are concentrated outside the ranks of gamblers with a severe mental health condition, which supports a public-health approach to ameliorating gambling-related harm. PMID- 29788763 TI - Progress toward development of a proteostasis drug for myocilin-associated glaucoma. PMID- 29788764 TI - Blood Sugar, Your Pancreas, and Unicorns: The Development of Health Education Materials for Youth With Prediabetes. AB - BACKGROUND: The obesity epidemic has led to an increase in prediabetes in youth, causing a serious public health concern. Education on diabetes risk and initiation of lifestyle change are the primary treatment modalities. There are few existing age-appropriate health education tools to address diabetes prevention for high-risk youth. AIM: To develop an age-appropriate health education tool(s) to help youth better understand type 2 diabetes risk factors and the reversibility of risk. METHOD: Health education tool development took place in five phases: exploration, design, analysis, refinement, and process evaluation. RESULTS: The project resulted in (1) booklet designed to increase knowledge of risk, (2) meme generator that mirrors the booklet graphics and allows youth to create their own meme based on their pancreas' current mood, (3) environmental posters for clinic, and (4) brief self-assessment that acts as a conversation starter for the health educators. CONCLUSION: Patients reported high likability and satisfaction with the health education tools, with the majority of patients giving the materials an "A" rating. The process evaluation indicated a high level of fidelity and related measures regarding how the health education tools were intended to be used and how they were actually used in the clinic setting. PMID- 29788762 TI - Distinct patterns of Internet and smartphone-related problems among adolescents by gender: Latent class analysis. AB - Background and objectives The ubiquitous Internet connections by smartphones weakened the traditional boundaries between computers and mobile phones. We sought to explore whether smartphone-related problems differ from those of computer use according to gender using latent class analysis (LCA). Methods After informed consents, 555 Korean middle-school students completed surveys on gaming, Internet use, and smartphone usage patterns. They also completed various psychosocial instruments. LCA was performed for the whole group and by gender. In addition to ANOVA and chi2 tests, post-hoc tests were conducted to examine differences among the LCA subgroups. Results In the whole group (n = 555), four subtypes were identified: dual-problem users (49.5%), problematic Internet users (7.7%), problematic smartphone users (32.1%), and "healthy" users (10.6%). Dual problem users scored highest for addictive behaviors and other psychopathologies. The gender-stratified LCA revealed three subtypes for each gender. With dual problem and healthy subgroup as common, problematic Internet subgroup was classified in the males, whereas problematic smartphone subgroup was classified in the females in the gender-stratified LCA. Thus, distinct patterns were observed according to gender with higher proportion of dual-problem present in males. While gaming was associated with problematic Internet use in males, aggression and impulsivity demonstrated associations with problematic smartphone use in females. Conclusions An increase in the number of digital media-related problems was associated with worse outcomes in various psychosocial scales. Gaming may play a crucial role in males solely displaying Internet-related problems. The heightened impulsivity and aggression seen in our female problematic smartphone users requires further research. PMID- 29788765 TI - Managing autism spectrum disorder in developing countries by utilizing existing resources: A perspective from Bangladesh. PMID- 29788766 TI - Design, synthesis and 3D QSAR based pharmacophore study of novel imatinib analogs as antitumor-apoptotic agents. AB - AIM: Imatinib possesses various mechanisms for combating cancer, making the development of imatinib analogs an attractive target for cancer research. METHOD: Two series of analogs were designed and synthesized, maintaining the essential pharmacophoric features in imatinib structure. The synthesized compounds were subjected to cell-based antiproliferative assays against nonsmall lung (A549) and colon cancer cell lines. In addition, flow cytometry cell cycle and caspase-3 colorimetric assays were performed. RESULTS: Most compounds showed potent anticancer activity against both cell lines with IC50 = 0.14-5.07 MUM. Three compounds demonstrated ability to reinforce cell cycle arrest at G1 stage in a manner similar to imatinib. In addition, they induced apoptosis via activation of caspase-3. PMID- 29788767 TI - Limitations of current monoclonal antibodies for plaque-type psoriasis and an outlook for the future. PMID- 29788768 TI - Short-Term Impact of tDCS Over the Right Inferior Frontal Cortex on Impulsive Responses in a Go/No-go Task. AB - Inhibitory control, a process deeply studied in laboratory settings, refers to the ability to inhibit an action once it has been initiated. A common way to process data in such tasks is to take the mean response time (RT) and error rate per participant. However, such an analysis ignores the strong dependency between spontaneous RT variations and error rate. Conditional accuracy function (CAF) is of particular interest, as by plotting the probability of a response to be correct as a function of its latency, it provides a means for studying the strength of impulsive responses associated with a higher frequency of fast response errors. This procedure was applied to a recent set of data in which the right inferior frontal gyrus (rIFG) was modulated using transcranial direct current stimulation (tDCS). Healthy participants (n = 40) were presented with a "Go/No-go" task (click on letter M, not on letter W, session 1). Then, one subgroup (n = 20) was randomly assigned to one 20-minutes neuromodulation session with tDCS (anodal electrode, rIFG; cathodal electrode, neck); and the other group (n = 20) to a condition with sham (placebo) tDCS. All participants were finally confronted to the same "Go/No-go" task (session 2). The rate of commission errors (click on W) and speed of response to Go trials were similar between sessions 1 and 2 in both neuromodulation groups. However, CAF showed that active tDCS over rIFG leads to a reduction of the drop in accuracy for fast responses (suggesting less impulsivity and greater inhibitory efficiency), this effect being only visible for the first experimental block following tDCS stimulation. Overall, the present data indicate that boosting the rIFG may be useful to enhance inhibitory skills, but that CAF could be of the greatest relevance to monitor the temporal dynamics of the neuromodulation effect. PMID- 29788770 TI - Synthesis & antitumor activity of epothilones B and D and their analogs. AB - Epothilone is a newly developed antitumor drug; its antitumor principle is to stop the cell cycle by binding to tubulin in tumor cells, promoting tubulin polymerization, inhibiting depolymerization of microtubules, and ultimately inducing apoptosis. There are many analogs of epothilone, such as epothilone B, epothilone D, ixabepilone, sagopilone, 21-amino-epothilone B and KOS-1584. Herein, the synthesis and antitumor activity of epothilones B and D were summed up. The antitumor activity of epothilone analogs was also compared. Synthesis of epothilone and its analogs is more complex, and choosing the proper synthetic method is very important. Moreover, these compounds have obvious antitumor effect. The epothilone and its analogs will continue to play an important role in the future treatment of tumors. PMID- 29788769 TI - Audit of Intrapartum Care Based on the National Guideline for Midwifery and Birth Services. AB - Providing high-quality maternity care is a worldwide health concern that necessitates regular assessment of intrapartum practice. In an observational study, we aimed to audit intrapartum care based on the National Guideline for Midwifery and Birth Services. Using quota sampling, a total of 200 pregnant women, admitted for normal vaginal delivery, were recruited from four educational hospitals in Tehran, Iran. An observational checklist was developed based on the national guideline to assess the quality of provided care. Content and face validity of the tool were checked and confirmed. Reliability of the observational checklist and questionnaire was confirmed using concurrent observation (intrarater reliability; r = .93) and test-retest ( r = .9) methods, respectively. We found that the compatibility of intrapartum care and the national guideline in different domains were as follows: history taking 88.3%, vital sign measurement 64.6%, performing Leopold's maneuver 38.5%, initial assessment 83.4%, labor care 22.5%, using pain relief methods 63.5%, labor progress assessment 71.5%, process of delivery 89.5%, and postpartum management 89.5%. The findings indicate that additional attention and monitoring are required to align current intrapartum care practices with the national guidelines. PMID- 29788771 TI - Understanding Design Vulnerabilities in the Physical Environment Relating to Patient Fall Patterns in a Psychiatric Hospital: Seven Years of Sentinel Events. AB - BACKGROUND: The influence of the physical environment on patient falls has not been fully explored in psychiatric units, despite this patient population's vulnerability and the critical role of the physical environment in patient safety. AIMS: The research objective is to describe the spatial and temporal pattern of falls occurrences and their location in relation to the levels of safety continuum model. METHOD: This article presents an exploratory case study design. Seven years of retrospective data on patient falls, yielding 818 sentinel events, in an 81-bed psychiatric hospital in the United States were collected and analyzed. Data focused on extrinsic factors for falls, emphasizing the physical environment. Through a content analysis of the sentinel event narratives, recorded by the hospital staff, this study explored patient falls related to location and elements of the physical environment. RESULTS: The analysis revealed that 15% of recorded falls were attributed to some aspect of or element within the physical environment. The most typical locations of falls were patient rooms (39%), patient bathrooms (22%), and dayrooms (20%). Also, the results identified patterns of environmental factors that appeared linked to increasing patients' susceptibility to falls. Risk factors included poor nighttime lighting, flooring surfaces that were uneven, and spaces that inadvertently limited visual access and supervision. CONCLUSIONS: The physical environment plays an often-unexamined role in fall events and specific locations. These results are deserving of further research on design strategies and applications to reduce patient falls in psychiatric hospital settings. PMID- 29788772 TI - Conceptualising "dose" in paediatric language interventions: Current findings and future directions. AB - Dose is a particularly important element of treatment for speech and language disorders, yet relatively little is known concerning how best to operationalise dose in clinical settings. This keynote provides an overview of dose as a theoretical and empirical concept and discusses recent findings that question whether "more is better" when treating children with language disorders. Given recent evidence showing that spaced treatments may result in optimal gains for children, I argue that low-frequency therapy sessions can be especially beneficial for children with language disorders when they are highly productive, providing children with high levels of dose. PMID- 29788773 TI - Corrigendum. PMID- 29788774 TI - The Standardization of Diagnostic Criteria for Fetal Alcohol Spectrum Disorder (FASD): Implications for Research, Clinical Practice and Population Health. AB - OBJECTIVE: Fetal Alcohol Spectrum Disorder (FASD) is a preventable disorder caused by maternal alcohol consumption and marked by a range of physical and mental disabilities. Although recognized by the scientific and medical community as a clinical disorder, no internationally standardized diagnostic tool yet exists for FASD. METHODS AND RESULTS: This review seeks to analyse the discrepancies in existing diagnostic tools for FASD, and the repercussions these differences have on research, public health, and government policy. CONCLUSIONS: Disagreement on the adoption of a standardised tool is reflective of existing gaps in research on the conditions and factors that influence fetal vulnerability to damage from exposure. This discordance has led to variability in research findings, inconsistencies in government messaging, and misdiagnoses or missed diagnoses. The objective measurement of the timing and level of prenatal alcohol exposure is key to bridging these gaps; however, there is conflicting or limited evidence to support the use of existing measures. PMID- 29788775 TI - What would help low-income families?: Results from a North American survey of 2-1 1 helpline professionals. AB - Almost half of young American children live in low-income families, many with unmet needs that negatively impact health and life outcomes. Understanding which needs, proactively addressed, would most improve their lives would allow maternal and child health practitioners and social service providers to generate collaborative solutions with the potential to affect health in childhood and throughout the life course. 2-1-1 referral helplines respond to over 16 million inquiries annually, including millions of low-income parents seeking resources. Because 2-1-1 staff members understand the availability of community resources, we conducted an online survey to determine which solutions staff believed held most potential to improve the lives of children in low-income families. Information and referral specialists, resource managers, and call center directors ( N = 471) from 44 states, Puerto Rico, and Canada ranked the needs of 2-1-1 callers with children based on which needs, if addressed, would help families most. Childcare (32%), parenting (29%), and child health/health care (23%) were rated most important. Across all childcare dimensions (e.g. quality affordable care, special needs care), over half of the respondents rated community resources inadequate. Findings will help practitioners develop screeners for needs assessment, prioritize resource referrals, and advocate for community resource development. PMID- 29788776 TI - Lenstar(r) LS 900 vs Pentacam(r)-AXL: Comparative study of ocular biometric measurements and intraocular lens power calculation. AB - PURPOSE:: Comparison of biometric measurements and calculation of intraocular lens with a new biometer (Pentacam(r)-AXL, Oculus, Germany) and a reference biometer (Lenstar LS 900(r), Haag-Streit AG, Switzerland), in order to assess the agreement between these two devices. SETTING:: Centro Hospitalar de Leiria, Portugal. MATERIALS AND METHODS:: Prospective, institutional study, in which measurements of axial length, anterior chamber depth from the corneal epithelium and endothelium to the anterior surface of the lens (anterior chamber depth ext and anterior chamber depth int), central corneal thickness and keratometry readings of the flattest and steepest meridians (K1 and K2) were obtained with the two systems. Intraocular lens calculation was also performed, using the Haigis, SRK/T and HofferQ formulas. RESULTS:: The study sample included 136 eyes of 79 patients. Of these, 42 were women and 37 were men. Statistically significant differences were found (p < 0.05, paired T test) in K1, K2 and central corneal thickness between the 2 biometers. Intraocular lens calculation with the Lenstar(r) and the Pentacam(r) with Haigis, SRK/T and HofferQ formulas showed statistically significant differences (p < 0.05 Paired T test). CONCLUSION:: Axial length measurements obtained with the Pentacam(r) and Lenstar(r) appear to be interchangeable, while measurements of anterior chamber depth, K1 and K2, and central corneal thickness do not appear to be interchangeable between different devices. Statistically significant differences were found in the calculation of intraocular lenses in all formulas used. PMID- 29788777 TI - In Response to Letters to the Editor From the American Diabetes Association and Eli Lilly in Regard to: Insulin Concentration in Vials Randomly Purchased in Pharmacies in the United States: Considerable Loss in the Cold Supply Chain. PMID- 29788778 TI - Validation of the short version of the Cognitive Emotion Regulation Questionnaire for Spanish children. AB - This study aimed to validate a short version of the Cognitive Emotion Regulation Questionnaire for Spanish kids (CERQ-Sk) based on the 18-item version available for adults. A sample of 654 children aged 7-12 years completed the CERQ-Sk and tests for depression and anxiety measures. Confirmatory factor analysis supported the 18-item version and the original nine-factor structure, which includes self blame, acceptance, rumination, positive refocusing, refocus on planning, positive reappraisal, putting into perspective, catastrophizing, and other-blame (comparative fit index = .99, Tucker-Lewis index = .98, root mean square error of approximation = .02). Internal consistency was adequate (ordinal alpha = .80), and the eight-week stability of this version was moderate (intraclass correlation = .69). Criterion validity was supported by correlations among self-blame, rumination, and catastrophizing (positive) and among positive reappraisal and depression and anxiety symptoms (negative). Results suggest that the short version of the CERQ-Sk is a valid and reliable instrument for assessing these cognitive emotion regulation strategies during the middle childhood developmental period. Clinicians and researchers will benefit from this briefer acceptable version when time is not available for the 36-item version. This study offers preliminary results for the first short version of the CERQ for children. PMID- 29788779 TI - Elevated Serum Lipid Peroxidation and Reduced Vitamin C and Trace Element Concentrations Are Correlated With Epilepsy. AB - BACKGROUND: Epilepsy is one of the chronic and heterogeneous epidemic neurological disorders leading to substantial mortality. The aim of the present study was to investigate the serum levels of malondialdehyde (MDA), vitamin C, and trace elements namely zinc (Zn), copper (Cu), and manganese (Mn) in epileptic patients of Bangladesh and to establish if there are any pathophysiological correlations. METHODS: This was a case-control study with 40 generalized epileptic patients and 40 healthy subjects as controls. Epilepsy was determined by the presence of seizure events with an abnormal electroencephalography and magnetic resonance imaging report of brain. RESULTS: Anthropometric parameters highlighted that age is a major risk factor of epilepsy and men are more prone to epilepsy than women. Blood serum analysis demonstrated significantly ( P < .001) higher values of MDA and lower level of vitamin C in the patient group (4.41 +/- 0.76 MUmol/mL and 18.31 +/- 0.84 MUmol/L, respectively) compared with control (1.81 +/- 0.70 MUmol/mL and 29.72 +/- 1.06 MUmol/L, respectively). Pearson's correlation analysis revealed a negative correlation between the serum level of MDA and vitamin C for both patient ( r = -0.023, P = .887) and control group ( r = -0.142, P = .383). This study also revealed that the trace elements (Zn, Cu) were significantly ( P < .05) lower in epileptics (68.32 +/- 4.59 and 50.81 +/- 2.54 MUg/dL, respectively) where the level of Mn in patients (187.71 +/- 9.04 MUg/dL) was almost similar to that of the control group ( P > .05). The univariate analysis demonstrated that zinc <70 MUg/dL (odds ratio = 3.56, P < .05) and copper <50 MUg/dL were associated (odds ratio = 14.73, P < .001) with an increased risk of epilepsy. Establishment of interelement relationship strongly supported that there was a disturbance in the element homeostasis of epileptic patients. CONCLUSIONS: The study results strengthen the role of lipid peroxidation, antioxidants and trace elements in the pathogenesis and warrant larger studies to investigate the association of these biochemical parameters with epilepsy. PMID- 29788781 TI - Purines and triazolo[4,3-e]purines containing pyrazole moiety as potential anticancer and antioxidant agents. AB - AIM: Targeting apoptosis regulators such as caspases aiming at inducing apoptosis is an attractive strategy in cancer therapy. MATERIALS & METHODS: 8-substituted purine incorporating pyrazole moiety were designed, synthesized and evaluated for their anticancer and antioxidant activities. RESULTS: Compounds 7a and 8a displayed potent and selective anticancer activity against lung cancer A549 cell line with low cytotoxicity on peripheral blood mononuclear normal cells. Compounds 7a and 8a induced caspase dependent apoptotic death and DNA damage in all cancer cell lines. In addition, compounds 2, 5, 6a, 7a, 8a, 8c, 11a, 11b and 12b showed good antioxidant activity higher than that of the standard ascorbic acid. CONCLUSION: Compounds 7a and 8a can be considered promising dual anticancer and antioxidant leads inducing caspase-dependent apoptotic death and DNA damage. PMID- 29788780 TI - Isoform selectivity of harmine-conjugated 1,2,3-triazoles against human monoamine oxidase. AB - AIM: There is little information available on the monoamine oxidase isoform selectivity of N-alkyl harmine analogs, which exhibit a myriad of activities including MAO-A, DYRK1A and cytotoxicity to several select cancer cell lines. RESULTS: Compounds 3e and 4c exhibited an IC50 of 0.83 +/- 0.03 and 0.43 +/- 0.002 MUM against MAO-A and an IC50 of 0.26 +/- 0.04 and 0.36 +/- 0.001 MUM against MAO-B, respectively. Molecular docking studies revealed pi-pi interactions between the synthesized molecules and aromatic amino acid residues. Conclusion & future perspective: The current study delineates the structural requirements for MAO-A selectivity and such information may be helpful in designing selective analogs for kinase, DYRK1A and harmine-based cytotoxics without apparent MAO enzyme inhibition. PMID- 29788782 TI - Are SGLT2 inhibitors or GLP-1 receptor agonists more appropriate as a second-line therapy in type 2 diabetes? PMID- 29788783 TI - A Mixed-Methods Approach to Understanding the Palliative Needs of Parkinson's Patients. AB - Parkinson's disease (PD) is the second-most common age-related neurodegenerative disorder. Despite recommendations for a palliative approach, little is known about what palliative needs are unmet by standard care. This study aims to (a) identify palliative needs of PD patients, (b) determine the relationship between palliative needs and health-related quality of life (HRQoL), and (c) probe into factors affecting HRQoL. PD patients and neurologists were recruited for a survey on palliative need; a subset of patients was interviewed. Significant differences between physicians and patients were found in Physical, Psychological, Social, Financial, and Spiritual domains. Physical and Psychological needs predicted HRQoL. Primary themes across interviews included (a) lack of healthcare education and (b) need for care coordination. Secondary themes included (a) the importance of support groups, (b) the role of spirituality/religion, and (c) the narrow perceived role of the neurologist. Findings highlight the importance of coordinated individualized care. PMID- 29788784 TI - Elbow flexion contractures in brachial plexus birth injury: function and appearance related factors. AB - PURPOSE: The purpose of this study was to identify the functional and aesthetic factors associated with an elbow flexion contracture in children with a brachial plexus birth injury who identified their elbow flexion contracture as a problem. MATERIALS AND METHODS: A retrospective cross-sectional study of children with brachial plexus birth injury between 7 and 18 years was conducted to compare the characteristics of children who had treatment for an elbow flexion contracture with those who did not. RESULTS: Fifty of the 200 children included in the study had treatment (one surgical release, 49 serial casting/splinting) for the elbow flexion contracture. Children who had treatment were an average 12.4 years of age, which was significantly older than those who did not have treatment. Elbow extension passive range of motion was an average -40.6 degrees prior to treatment. Stepwise logistical regression model indicated that children who had treatment had greater severity in elbow contracture, higher Brachial Plexus Outcome Measure Activity scores, and lower Brachial Plexus Outcome Measure Self Evaluation Appearance scores. CONCLUSIONS: In addition to severity of contracture and function, perceived appearance of the limb is important factor to evaluate in the management of elbow flexion contractures. Implications for rehabilitation Priority is often given to evaluate the functional implications of elbow flexion contractures in brachial plexus birth injury to determine recommendations for rehabilitation interventions such as serial casting and splinting. Findings in this study indicate that severity of contracture, upper extremity activity function, and perceived upper extremity appearance are important factors in the management of elbow contractures. In addition to upper extremity function, routine evaluation of perceived upper extremity appearance in children and adolescents is important in the management of elbow flexion contractures. PMID- 29788785 TI - Impaired serotonin communication during juvenile development in rats diminishes adult sperm quality. AB - : Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p chloroamphetamine (PCA) (0.03, 0.06, or 0.12 mg). At 65 days of age, rats were euthanized and sperm density, motility, membrane integrity, mitochondrial function, and abnormalities were evaluated in gametes from the vas deferens. Inhibition of synthesis of intratesticular serotonin by PCA diminished the concentrations of testosterone and follicle-stimulating hormone (FSH) but luteinizing hormone (LH) levels were unaltered. Sperm density was not modified in animals injected with the different concentrations of PCA. In contrast, the percentage of sperm with abnormalities increased and the sperm membrane integrity decreased in animals injected at higher PCA concentrations. The functionality of sperm mitochondria in PCA-injected animals decreased only at the highest PCA dose. Our results indicate that testicular serotonin plays a role in testosterone synthesis and in the normal development of sperm, and blocking its effects disrupts the hormonal communication between the testis and hypophysis. ABBREVIATIONS: SS: saline solution; PCA: p-chloroamphetamine; FSH: follicle stimulating hormone; LH: luteinizing hormone; TPH: tryptophan hydroxylase; MAO: monoamine oxidase; AC: absolute control group; PI: propidium iodide; FLICA: fluorescence inhibitor of caspase; 3beta-HSD: 3beta-hydroxysteroid dehydrogenase; 17-KSR: 17-ketosteroid reductase; DHT: 5-dihydrotestosterone. PMID- 29788786 TI - Emergency room visits for chronic obstructive pulmonary disease in Illinois counties: An epidemiological study based on the Social Ecological Model. AB - Objectives This study aimed to determine the predictive capability of the Social Ecological Model for emergency room visits for acute exacerbation of chronic obstructive pulmonary disease. Methods County-level secondary data ( n = 102) on emergency room visits for chronic obstructive pulmonary disease were retrieved from the Illinois Department of Public Health for 2016. Data for variables operationalized from the intrapersonal, interpersonal, institutional, community, and public policy levels of the Social Ecological Model were retrieved from several sources. Geographic information system software was used to examine the spatial distribution of emergency room visits for chronic obstructive pulmonary disease in Illinois. Robust linear regression analysis was used to examine significant predictors of emergency room visits for chronic obstructive pulmonary disease. Results A regression model with all five levels of the Social Ecological Model accounted for 50% of the variability in emergency room visits for chronic obstructive pulmonary disease, F(24,77) = 4.62, p < 0.001. Statistically significant predictors of emergency room visits for chronic obstructive pulmonary disease were observed within the interpersonal, institutional, and community levels of the Social Ecological Model. Discussion Community health practitioners working to develop programs aimed at controlling chronic obstructive pulmonary disease exacerbations in Illinois should consider multiple levels of influence. PMID- 29788788 TI - Diagnostic Performance of the Electroencephalogram in the Elderly Manifesting With Episodes of Unresponsiveness. AB - This study aimed to determine diagnostic performance of the EEG in diagnosing seizures and to ascertain risk factors associated with seizures in the elderly presenting with episodes of unresponsiveness compared with younger patients. This is a cross-sectional study. Only EEGs requested with indication of transient unresponsiveness (TUR) were included. Patients were divided into 2 groups, younger (aged 18-49 years) and elderly (aged >60 years). The EEG was an index test. Reference standard, independently verified by 2 board-certified neurologists, was a clinical diagnosis of presence or absence of epilepsy/probable seizures. Univariate and multivariate analyses were performed to ascertain associated risk factors for epilepsy/probable seizures. Among 2187 total EEG recordings, 244 (11.16%) recordings were requested with indication of TUR. A total of 156 patients (50 younger and 106 elderly) were recruited for analysis. Prevalence of epilepsy/probable seizures in patients with TUR was 26.9%. Prevalence of interictal epileptiform discharges was 16% in the younger and 12.3% in the elderly. Overall diagnostic performance was poorer in the elderly. Associated risk factors for having seizures were presence of intermittent slow waves in the younger and presence of positive motor signs as well as presence of nonepileptiform abnormalities in the elderly. Prevalence of seizures and interictal epileptiform discharges was low in the elderly who manifests with TUR. Overall diagnostic performance of the EEG in diagnosing seizures was poorer in the elderly mainly due to low sensitivity. When we encounter patients with TUR, thorough and detailed history is still a mainstay of a diagnosis of seizures, not the EEG results. PMID- 29788789 TI - Measuring Functional Impairment in Children and Adolescents: Psychometric Properties of the Columbia Impairment Scale (CIS). AB - The role of measuring functional impairment holds an important place in research, clinical practice, and service provision for children and adolescents. Responding to the growing need to measure serious emotional disturbances at the local, state, and national level, the Columbia Impairment Scale (CIS) was developed in the early 1990s and has remained one of the several popular scales for assessing functional impairment. However, despite the growing popularity of the instrument in research and practice, only a few studies to date have specifically examined the psychometric properties of the CIS. In this article, we describe the results of the first item response theory analysis of the CIS utilizing nationally representative data from the Medical Expenditure Panel Survey ( N = 69,966). The results of our analysis lend support to the essential unidimensionality of the CIS and demonstrate that the scale is most reliable for those who exhibit high levels of functional impairment. Given the psychometric properties of the scale identified by our analysis, we contend that the CIS is a viable measure in the ongoing efforts to establish a national epidemiologic surveillance system to track the prevalence and impact of serious emotional disturbances in children and adolescents. PMID- 29788787 TI - Review of bioactive secondary metabolites from marine bryozoans in the progress of new drugs discovery. AB - Marine bryozoans play an important role for the discovery of novel bioactive compounds among marine organisms. In this review, we summarize 164 new secondary metabolites including macrocyclic lactones, sterols, alkaloids, sphingolipids and so forth from 24 marine bryozoans in the last two decades. The structural features, bioactivity, structure-activity relationship, mechanism and strategies to address the resupply of these scarce secondary metabolites are discussed. The structural and bioactive diversity of the secondary metabolites from marine bryozoans indicated the possibility of using these compounds, especially bryostatin 1 (1), bryostatin analog (BA1), alkaloids (50, 53, 127-128 and 134 139), sphingolipids sulfates (148 and 149) and sulfur-containing aromatic compound (160), as the starting points for new drug discovery. PMID- 29788790 TI - EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt Jakob Disease. AB - Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P < .006). On neuroimaging, diffusion restriction in the cortex ( P = .001), caudate ( P < .001), and putamen ( P = .001) was more frequent in CJD. Periodic sharp wave complexes ( P = .001) and generalized suppressed activity ( P = .008) were more common on initial EEG in CJD. On serial EEGs, generalized periodic discharges ( P = .004), generalized suppressed activity (P=0.008), and periodic sharp wave complexes ( P < .001) were detected more in CJD. This study shows that there are a number of differentiating features between CJD and VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions. PMID- 29788791 TI - Nicotine metabolite ratio and smoking outcomes using nicotine replacement therapy and varenicline among smokers with and without psychiatric illness. AB - INTRODUCTION: It has been suggested that the effectiveness of nicotine replacement smoking cessation pharmacotherapy may be enhanced by assessing rates of nicotine metabolism using the nicotine metabolite ratio - which reflects differences in the activity of the CYP2A6 hepatic enzyme - and titrating doses appropriately. To date, supporting evidence is equivocal, with little information regarding the assessment and effectiveness of the nicotine metabolite ratio among smokers with psychiatric conditions. METHODS: The nicotine metabolite ratio of 499 smokers from the FLEX trial was determined using urine samples obtained at baseline. They were randomized to receive either: standard transdermal nicotine (nicotine replacement therapy); extended nicotine replacement therapy + adjunct nicotine agent; or varenicline. Primary cessation outcomes were seven-day point prevalence at 5, 10, 22, and 52 weeks post-target quit date, comparing across treatment and psychiatric status. Our principal analysis employed logistic regression (outcome: abstinence), using slow metabolizers as the reference category. RESULTS: No differences were observed by nicotine metabolite ratio classification (slow, moderate, fast) with respect to any demographic or smoking related variables. Nicotine metabolite ratio class did not predict smoking cessation in either the overall sample, or by treatment condition at any time point (week 52 moderate metabolizers: odds ratio 1.34, 95% confidence interval (0.68-2.63), p=0.394; fast metabolizers: odds ratio 1.04 (0.56-1.91), p=0. 906). CONCLUSION: Our results did not find any associations between nicotine metabolite ratio and cessation outcomes among smokers using nicotine replacement therapy or varenicline with and without lifetime psychiatric conditions. PMID- 29788792 TI - Turning the next generation of clinical physicians into management leaders: The integration of healthcare management into medical training. PMID- 29788793 TI - Environmental enrichment prevents pup mortality in laboratory mice. AB - Early death of mouse pups is a commonly known problem in breeding mice colonies, which is still often regarded as 'normal' or is even overlooked due to the counting procedures applied. As reduced breeding performance probably indicates reduced well-being, this seems to be an underestimated welfare issue in laboratory mouse breeding. The present study compares the influence of three different forms of enrichment in breeding cages on infant survival rate and development of C57BL/6J mice. Our data reveal that lack of enrichment results in greater preweaning pup mortality, reduced weight and delayed development. Changing the environmental conditions after birth cannot prevent litter loss but improves the development of pups born in impoverished environments. Overall, our results underline the importance of early counting of mice for optimizing refinement strategies to ensure well-being and breeding success. PMID- 29788794 TI - Implementation of an Allergic Reaction Reporting Tool for School Health Personnel: A Pilot Study of Three Chicago Schools. AB - Food allergy (FA) impacts 8% of U.S. children, thus it is critical to document allergic reactions to assist schools in managing FAs. We implemented and evaluated an online tool to assist school health personnel in tracking the characteristics of allergic reactions occurring at schools. The Online School Allergic Reaction Registry (OScARR) was modified from the Epinephrine Administration Form developed by the Massachusetts Department of Public Health, adapted for integration into existing school health records, and implemented in three Chicago schools during the 2016-2017 school year. All allergic reactions occurring at participating schools were recorded by school nurses. Twenty-five percent of the 20 allergic reactions reported were characterized as anaphylaxis by school nurses. School nurses reported that they would recommend OScARR for use in other schools. Detailed data obtained from three Chicago schools underscore the importance of proper documentation to improve the understanding of the causative allergen and location and management of allergic reactions in schools. PMID- 29788795 TI - Distress Tolerance Intervention for Improving Self-Management of Chronic Conditions: A Systematic Review. AB - BACKGROUND: The inability to tolerate distress can negatively influence effective self-management (SM) of chronic conditions by interfering with the ability to focus on illness needs and impairing problem-solving and prioritizing capabilities, as well as engagement in SM activities. Interventions to increase distress tolerance offer a holistic approach to chronic disease SM and may enhance the individual's ability to apply SM skills and resources to improve quality of life and overall health. The purpose of this systematic review was to deepen understanding of the relationships among distress tolerance and goal oriented problem-solving as an aspect of chronic disease SM. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were used to develop a search strategy, selection criteria, screening, and identification and extraction procedures. PubMed, CINAHL, PsychInfo, and Scopus were searched from 2006 to December 2017 using the following search terms: distress tolerance, chronic conditions, self-management. RESULTS: Across the 11 studies included in the literature review, there was a high level of heterogeneity in the use of subjective and objective measures to assess distress tolerance, and only one study included instruments to measure goal-oriented problem-solving, the target of distress tolerance interventions that are assumed to influence the selected health outcome. CONCLUSION: Further research is needed on the efficacy of distress tolerance interventions for improving SM of chronic conditions. Theory-driven interventions that explicate the precise goal-oriented problem-solving and SM behaviors that are expected to change as a result of the distress tolerance intervention will provide insight on the efficacy of the intervention and help close the theory-practice gap. PMID- 29788796 TI - Off-Hours Admissions and Mortality in PICU Without 24-Hour Onsite Intensivist Coverage. AB - OBJECTIVE: To evaluate whether the off-hours admission has any effect on risk adjusted mortality and length of stay for nonelective patients admitted to a pediatric intensive care unit (PICU) without 24-hour in-house intensivist coverage. DESIGN: Prospective cohort study. SETTING: A 34-bed tertiary PICU. PATIENTS: All consecutive nonelective patients aged 0 to 14 years admitted from January 2012 to June 2015. MEASUREMENTS AND MAIN RESULTS: A total of 1254 patients were nonelectively admitted to the PICU. They were categorized according to time of PICU admission as either office hours (07:30 to 16:30 from Sunday to Thursday and whenever an intensivist is present in the ICU) or off-hours (16:30 to 07:30, Friday and Saturday and public holidays). Standardized mortality rates (SMRs) of patients admitted during off-hours were compared to SMRs of patients admitted during office hours using Pediatric Risk of Mortality (PRISM2) score. Multivariate logistic regression was used to assess the effect of time of admission on outcome after adjustment for severity of illness using the PRISM2. The mortality observed in the office-hours group was 9.4% and in the off-hours group was 8.1%. The PRISM2-based SMR was 0.83 (95% confidence interval [CI]: 0.43 1.47) for the office-hours group and 0.68 (95% CI: 0.34-1.36) for the off-hours group. No significant differences in length of ICU stay or duration of mechanical ventilation were observed between patients admitted during off-hours and those admitted during office hours. In the logistic regression model, off-hours admission was not significantly associated with a higher mortality (odds ratio: 0.85, 95% CI: 0.57-1.27; P = .44). CONCLUSIONS: The absence of an in-house intensivist during off-hours is not associated with an increase in mortality, length of ICU stay, or duration of mechanical ventilation for patients admitted to our pediatric ICU. PMID- 29788798 TI - Optimizing therapy in bortezomib-exposed patients with multiple myeloma. AB - INTRODUCTION: Multiple myeloma prognosis has improved significantly during the past decade, with survival prolongation mainly due to the incorporation of novel agents. Bortezomib represents one of the main backbone agents of antimyeloma treatment. Areas covered: This review aims to identify possible and available therapeutic options for patients who experience disease refractoriness following bortezomib exposure. Expert commentary: For patients who finally relapse after bortezomib exposure treatment strategy should be individualized. For patients with disease resistant to bortezomib, the combination of lenalidomide dexamethasone with a monoclonal antibody seems to be the most optimal choice for second-line treatment. For third line, pomalidomide-based regimens can be effective even in bortezomib refractory patients. Several novel agents are currently under investigation in order to treat multi-refractory disease.G. PMID- 29788797 TI - Characteristics of the Epithelial-Mesenchymal Transition in Primary and Paired Metastatic Canine Mammary Carcinomas. AB - The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tumor types, including mammary tumors. In this study, we evaluated E-cadherin and vimentin immunolocalization in primary canine mammary carcinomas (20 cases) and their respective metastases, as well as their relationship with the core regulators SNAIL/SLUG. To assess the number of cells undergoing the process of EMT, we quantitated double-positive (E cadherin+/vimentin+) cells using immunofluorescence, via cell counting and image analysis. In addition, SNAIL/SLUG expression was evaluated by established immunohistochemical methods. Primary tumors had significantly more E cadherin+/vimentin+ co-expression than their paired respective lymph node or distant metastasis, respectively. Furthermore, the percentage of E cadherin+/vimentin+ cells in grade II and III carcinomas was significantly higher than in grade I tumors. Primary tumors had significantly higher SNAIL/SLUG expression when analyzed based on the percentage of positive cells compared with their respective distant metastases in pairwise comparisons. An inverse correlation was noted between SNAIL/SLUG immunoreactivity and percentage of E cadherin+/vimentin+ immunopositive cells in primary tumor samples when SNAIL/SLUG immunoreactivity was grouped into 2 categories (high versus low) based on percentage-positive staining. These results show a positive correlation between E cadherin+/vimentin+ cells and higher tumor grade, establish differences between primary tumor and their respective metastases, and provide further support that EMT plays a critical role in the metastasis of canine mammary carcinoma. Furthermore, these data suggest that modulation of this process could provide greater therapeutic control and provide support for further research to determine if E-cadherin+/vimentin+ co-immunoreactivity imparts predictive value in the clinical outcome of patients with canine mammary carcinomas. PMID- 29788800 TI - Relationship between YKL-40 and pulmonary arterial hypertension in systemic sclerosis. AB - OBJECTIVES: Systemic sclerosis (SSc) is an intractable connective tissue disease that causes skin and organ fibrosis. Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) affect its prognosis. YKL-40 protein impacts inflammation and tissue remodeling. Therefore, we evaluated the utility of YKL-40 blood levels in identifying patients with SSc complicated by PAH, as confirmed by immunohistochemistry (IHC) examination. METHODS: We retrospectively analyzed 78 patients with SSc and performed IHC on 7 normal and 7 SSc skin samples in the Japanese population. Age-adjusted YKL-40 serum levels were analyzed. RESULTS: YKL-40 age percentile was significantly elevated in SSc patients. There was no difference between patients with SSc with and without ILD and PAH. YKL-40 age percentile was greater in patients with PAH complication. YKL 40 immunostaining was negative in normal skin and prominent in the subcutaneous vascular wall of all SSc samples. Receiver operating characteristic (ROC) curve analysis indicated that YKL-40 age percentile correctly differentiated between patients with and without PAH with a sensitivity of 80% and a specificity of 94.1%. CONCLUSION: A higher YKL-40 level with PAH may be reflective of angiogenesis due to capillary injury in SSc. YKL-40 may offer a useful and easily applicable diagnostic biomarker of SSc complicated with PAH. PMID- 29788799 TI - Management of the left subclavian artery during TEVAR - complications and mid term follow-up. AB - BACKGROUND: Numerous conditions that affect the boundary between the aortic arch and descending aorta are treated with thoracic endovascular aortic repair (TEVAR). In 40 % of cases, coverage of the left subclavian artery (LSA) cannot be prevented. Subsequently, neurological complications such as stroke or ischemia of the left upper extremity may develop. However, the actual risk of these complications is subject to considerable controversy. The optimal treatment approach, specifically the question whether primary revascularization of the LSA should be performed in all cases, is unclear. PATIENTS AND METHODS: The present retrospective study analyzed the short- and mid-term results of patients treated with TEVAR with complete coverage of the LSA. The postoperative protocol consisted of clinical and noninvasive examinations as well as morphological imaging. Survival, complication, and reintervention rates were recorded. RESULTS: A total of 40 patients, undergoing TEVAR with complete coverage of the LSA between January 2010 and December 2014 were analyzed retrospectively. The 30-day survival rate was 95 %, the survival one year after performed TEVAR was 67.5 %. The average follow-up was 1.5 years. After TEVAR procedure with complete coverage of the LSA, only one patient (2.5 %) developed critical ischemia of the left arm immediately after aortic stent implantation, requiring revascularization by transposition of the LSA. Anterior spinal artery syndrome occurred in another patient (2.5 %) immediately following TEVAR. During follow-up examinations, all patients showed a compensated arterial arm status. None of the patients developed new neurological deficits during the follow-up period. CONCLUSIONS: The study shows that performing TEVAR without primary revascularization of the LSA was justifiable in our cohort. An important risk factor of developing cerebral ischemia seems to be insufficient collateralization through the circle of Willis. PMID- 29788801 TI - Perioperative noninvasive cardiac output monitoring in parturients with singleton and twin pregnancies undergoing cesarean section under spinal anesthesia with prophylactic phenylephrine drip: a prospective observational cohort study. AB - PURPOSE: Spinal anesthesia is considered the gold standard anesthetic technique for cesarean deliveries (CDs) but is associated with a high rate of hypotension. The recent international consensus recommends continuous prophylactic phenylephrine infusion (PPI) administered throughout CD to prevent hypotension. However, little information is available on the hemodynamic profiles of women with twin pregnancies as compared to singleton pregnancies perioperatively. Therefore, in this study, we aim to compare maternal hemodynamic changes both intraoperatively and postoperatively with the use of the NICAS bioimpendence monitor in healthy singleton versus twin parturients undergoing CD deliveries with spinal anesthesia with PPI. MATERIALS AND METHODS: After IRB approval and signed informed consent, healthy term women with either twin or singleton pregnancies undergoing spinal anesthesia for uncomplicated CD were enrolled. The following data were collected - cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), and total peripheral resistance (TPR). Measurements were measured at five time points: (1) before arrival in OR, (2) after spinal anesthesia with PPI, (3) after beginning of oxytocin infusion, (4) in post anesthesia care room, (5) 24 hours postoperatively, and (6) 48 hours postoperatively. All parturients received standardized spinal solution consisting of 12 mg hyperbaric bupivacaine, 20 ug fentanyl and 100-ug preservative-free morphine. PPI administered was titrated to preserve blood pressure to 20% of baseline blood pressure and stopped at the end of surgery. Oxytocin was administered as a continuous infusion (20-units/1000 cm3 Ringer's lactate) at a rate of 100 cm3/h. RESULTS: One hundred and thirty seven parturients with singleton pregnancies and 27 parturients with twin pregnancies completed the study. There were no significant differences between groups in age or BMI. Intraoperatively, there was no difference in any hemodynamic parameter. However, postoperatively at all three times women with twin pregnancies had higher MAP, lower CO and higher TPR compared with parturients with singleton pregnancies. CONCLUSIONS: There were significant hemodynamic changes postoperatively but not intraoperatively in parturients with twin pregnancies compared to women with singleton pregnancies. These changes need to be further investigated. PMID- 29788802 TI - Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers. AB - OBJECTIVE: This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers. METHODS: A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a single menthol condition per session). In each test session (performed at least 24 hours apart), a random order of saline, and two different nicotine infusions of 0.25 mg and 0.5 mg/70 kg of bodyweight were administered, one hour apart, concurrent with menthol inhalation. RESULTS: While menthol did not alter the positive subjective effects of nicotine, menthol significantly enhanced aversive effects of nicotine in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers. In addition, menthol preferring smokers reported blunted positive subjective responses to nicotine and less severe nicotine withdrawal after overnight nicotine deprivation. Finally, compared to non-menthol-preferring smokers, menthol-preferring smokers had a significantly lower baseline nicotine metabolite ratio indicating slower nicotine metabolism within our sample of menthol-preferring smokers. CONCLUSIONS: Our findings did not support an enhancement of nicotine's positive subjective effects from inhaled menthol. However, as compared to non-menthol-preferring smokers, menthol-preferring smokers had blunted positive subjective responses to nicotine and reduced overnight withdrawal severity that may be partly due to inhibition of nicotine metabolism from chronic exposure to inhaled menthol. Collectively, these results reveal a more complex and nuanced role of inhaled menthol in smokers than previously recognized. PMID- 29788804 TI - Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress. AB - Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short- and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure. PMID- 29788803 TI - Establishment of a spontaneously transformed cell line (JU-PI) from a myxoinflammatory fibroblastic sarcoma. AB - Myxoinflammatory fibroblastic sarcoma is a soft-tissue neoplasm most frequently found in the distal extremities of middle-aged adults. Most myxoinflammatory fibroblastic sarcoma are low-grade tumors with propensity for local recurrence after incomplete removal. We report a myxoinflammatory fibroblastic sarcoma which developed in the foot of a 41-year-old male and showed an exceptionally aggressive course with metastatic spread and fatal outcome within 16 months. We managed to establish a spontaneously transformed continuous cell line, called JU PI, from a metastatic lesion. The JU-PI cells have a sub-tetraploid karyotype including the 1;10 chromosomal translocation and amplification of the proximal end of 3p; these features are considered genetic signatures of myxoinflammatory fibroblastic sarcoma. Both the primary tumor and the JU-PI cells showed nuclear expression of the TFE3 transcription factor but TFE3-activating chromosomal rearrangements were not found. To our knowledge, JU-PI is the first established myxoinflammatory fibroblastic sarcoma cell line. JU-PI cells offer a tool for investigating the molecular oncology of myxoinflammatory fibroblastic sarcoma. PMID- 29788805 TI - Proximal row carpectomy, scaphoidectomy with midcarpal arthrodesis or midcarpal tenodesis: when and how to use. AB - I report my personal experience over three decades in the treatment of carpal collapse due to scapholunate collapse and scaphoid nonunion. I have used the proximal carpal row resection performed through palmar approach, the scaphoidectomy and double-column midcarpal arthrodesis, and scaphoidectomy with midcarpal tenodesis. Diagnostic arthroscopy is essential for staging and surgical decision making regarding the type of treatment. The details of the surgical techniques, tips, results and possible complications are described for each method. The advantage of the proximal row carpectomy by palmar approach is the early permitted rehabilitation with better recovery of wrist motility in comparison with the traditional technique. The advantage of the double-column midcarpal arthrodesis lies in its ease of execution. The midcarpal tenodesis is an excellent intervention from the conceptual point of view even if over time there is a progressive carpal collapse even in absence of symptoms. PMID- 29788806 TI - Corrigendum. PMID- 29788807 TI - Evidence for telehealth group-based treatment: A systematic review. AB - Background Interest in the use of telehealth interventions to increase access to healthcare services is growing. Group-based interventions have the potential to increase patient access to highly needed services. The aim of this study was to systematically review the available literature on group-based video teleconference services. Methods The English-language literature was searched using Ovid MEDLINE, PubMed, PsycINFO and CINAHL for terms related to telehealth, group therapy and support groups. Abstracts were reviewed for relevance based on inclusion criteria. Multiple study types were reviewed, including open-label, qualitative and randomised controlled trial study designs. Data were compiled regarding participants, study intervention and outcomes. Specific areas of interest were the feasibility of and satisfaction with telehealth technology, as well as the effect of video teleconference delivery on group dynamics, including therapeutic alliance. Results Forty published studies met the inclusion criteria and were included in the review. Six were randomised controlled trials. Among the studies, there was a broad range of study designs, participants, group interventions and outcome measures. Video teleconference groups were found to be feasible and resulted in similar treatment outcomes to in-person groups. However, few studies were designed to demonstrate noninferiority of video teleconference groups compared with in-person groups. Studies that examined group process factors showed small decreases in therapeutic alliance in the video teleconference participants. Conclusions Video teleconference groups are feasible and produce outcomes similar to in-person treatment, with high participant satisfaction despite technical challenges. Additional research is needed to identify optimal methods of video teleconference group delivery to maximise clinical benefit and treatment outcomes. PMID- 29788808 TI - Epidemiology of cutaneous lupus erythematosus and the associated risk of systemic lupus erythematosus: a nationwide cohort study in Denmark. AB - Objectives The objectives of this paper are to describe the epidemiology of cutaneous lupus erythematosus (CLE) and its subtypes in Denmark, and to investigate the probability of receiving a subsequent diagnosis of systemic lupus erythematosus (SLE) and the related time course. Methods A nationwide registry based cohort study was conducted in Denmark based on data from the Danish National Patient Registry from 1998 to 2013 using International Classification of Diseases, Revision 10. Results We identified 2380 patients with CLE. The annual incidence rate (IR) of CLE was 2.74/100,000 with a female:male ratio of 4:1. During 12,047 person-years of follow-up, 8% were diagnosed with SLE. The probability of receiving a subsequent diagnosis of SLE was 12.9% after 10 years taking death as a competing risk into consideration, and the probability was highest among women and patients diagnosed with subacute CLE. The median time until a diagnosis of SLE was 2.05 years. Conclusions This is the first nationwide study on CLE in Denmark. Although we found the annual IR of CLE and the risk of receiving an additional diagnosis of SLE to be lower than previously described, continued monitoring and thorough information for patients with CLE is important due to the inherent risk of SLE. PMID- 29788809 TI - Using hydroxychloroquine and protecting the retina. PMID- 29788810 TI - Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience. AB - Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002-2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 +/- 8.6 and the disease duration was 6.1 +/- 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis ( p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use >= six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found. PMID- 29788811 TI - Central ECMO for circulatory failure following pediatric liver transplantation. AB - We describe the case of a 4-year-old male with a past medical history significant for nephrotic syndrome, short-bowel syndrome and fulminant hepatic failure status post (s/p) liver transplant (LT) who developed early post-transplant allograft dysfunction (hyperbilirubinemia, coagulopathy) and septic shock requiring central extracorporeal membrane oxygenation (ECMO). He remained on ECMO for 85 hours before he was decannulated without event and later underwent repeat LT. This case highlights the potential of central ECMO to provide the circulatory output necessary to reverse distributive shock physiology in patients with sepsis and hepatic dysfunction following LT. Furthermore, this is the first documented example of central ECMO as a bridge to recovery for repeat LT. PMID- 29788812 TI - A novel technique to visualize true lumen in endovascular treatment of the occlusive carotid dissection and the usefulness of external-internal carotid collateral channel. AB - Background Dissection of the internal carotid artery (ICA) can cause occlusion or severe stenosis and is known to be one of the major causes of ischemic stroke in the young. Endovascular treatment is one of the useful options for carotid dissections, but passing the guidewire through the occlusion (lesion-cross) and confirmation of the true lumen are sometimes difficult. Case presentation A 40 year-old right-handed man complaining of dysarthria and gait disturbance consulted our hospital. Magnetic resonance imaging and angiography revealed right ICA dissection. Because of worsening symptoms with conservative treatment, we performed endovascular treatment. Prior to the lesion-cross, a microcatheter was navigated to the third segment of the internal maxillary artery and a balloon guiding catheter was navigated to the proximal ICA. Under balloon occlusion of the ICA, superselective angiography via the ipsilateral maxillary artery and slow evacuation from the balloon-guiding catheter were performed. Thereafter, the course of the true lumen was clearly visualized, and we were able to navigate another microcatheter without difficulty. Subsequently, angioplasty and stent placement were successfully accomplished. Conclusion We presented a case of ICA dissection and demonstrated a novel technique for a safe lesion-cross for occlusive ICA dissection. PMID- 29788813 TI - De novo aneurysm formation of a feeder artery after embolization of a dural arteriovenous fistula and rupture during second embolization. AB - Objective Hemorrhage during embolization of dural arteriovenous fistula (DAVF) is a rare but devastating complication. This study was undertaken to analyze the causes of hemorrhage and avoid complication. Methods The clinical data of a case of DAVF with hemorrhagic complication were retrospectively collected and analyzed. Results The patient in this case presented with DAVF and two de novo aneurysms of a feeder artery after the first embolization. One de novo aneurysm ruptured during the second embolization of the DAVF because of hemodynamic change. Computed tomography showed a subdural hematoma, and surgical exploration was emergently performed. However, the patient died at postoperative day 10. Conclusions De novo aneurysm of a feeder artery may form after embolization of DAVF because of hemodynamic change. It has a high risk of rupture and should be a primary consideration in embolization of DAVF. PMID- 29788814 TI - Advancing a Model of Secondary Trauma: Consequences for Victim Service Providers. AB - A burgeoning body of scholarship is attempting to understand, normalize, and ameliorate the emotional strain of victim service provision. The literature, however, has yet to fully theorize the hazardous process of empathetic engagement with victims. As a result, concepts, mechanisms, and outcomes are often conflated, making it difficult to understand the etiological path of this occupational risk. The goal of this article is to attend to this gap by accomplishing three objectives. The first is to engage with the perspective of symbolic interaction to theoretically ground a conceptual model of secondary trauma. The second objective is to propose a model of secondary trauma that acknowledges its inherently interactional, interpretive, and, thus, vicariously transmissible nature. The third objective is to begin the work of empirically supporting this model with data from a sample of victim service providers ( n = 94) collected using in-depth interviews, focus groups, ethnographic participant observation, and community-based participatory research. Our findings suggest that victim service provision, in the form of empathetic engagement, can blur the boundary between self and other, and lead to a sense of damage in the self that manifests in unreliable self-agency, untrustworthy coherence of other, desensitized self-affectivity, and fractured self-history. This work has significant implications. We illustrate an important paradox by showing how victim service provision can be helpful to victims but harmful to providers. We also offer a pathway for reducing this harm. By specifying mechanisms of damage, the model can be used to inform policies and practices supportive of victim service providers' health and well-being. PMID- 29788815 TI - Effect of Magnesium Loading Dose on Insulin Resistance in Patients With Stress Induced Hyperglycemia: A Randomized Clinical Trial. AB - OBJECTIVES: There is currently no evidence that whether magnesium supplementation would improve stress-induced hyperglycemia (SIH) in critically ill patients. In this study, effects of magnesium loading dose on insulin resistance (IR) indices were evaluated in critically ill patients without diabetes having SIH. METHODS: Seventy critically ill patients with SIH were assigned to receive a loading dose of magnesium (7.5 g of magnesium sulfate in 500 mL normal saline as intravenous infusion over an 8-hour period) or placebo. Changes in baseline of serum and intracellular magnesium and serum adiponectin (AD) levels, homeostasis model assessment of IR (HOMA-IR), and HOMA-AD ratio were assessed in this study. RESULTS: Serum and intracellular magnesium levels increased significantly in patients in the magnesium group ( P < .001). At day 3, there were significant differences between the magnesium group and the placebo group in the mean changes from baseline in the HOMA (between-group difference: -0.11; 95% confidence interval [CI]: -0.19 to -0.01; P = .02), the AD (between-group difference: 0.94; 95% CI: 0.41-1.48; P = .04), and the HOMA-AD ratio (between-group difference: 0.03; 95% CI: -0.04 to -0.01; P < .001). CONCLUSION: In the present study, a single-loading dose of intravenous magnesium improved IR indices in critically ill patients with SIH. PMID- 29788816 TI - Is maternal serum relaxin associated with preterm delivery in Chinese pregnant women? A meta-analysis. AB - OBJECTIVE: A meta-analysis was performed to study the relationship between serum relaxin and preterm delivery in women with singleton pregnancies without estrogen stimulation. METHODS: Cohort and case-control studies were identified through searching databases (PubMed, Embase, Ovid, CBM, Wan fang, VIP, and CNKI). We carried out a continuous variable meta-analysis. The outcome was preterm delivery (gestation age <37 weeks). RESULTS: Fifteen studies were included, involving 1607 women with a singleton pregnancy. The pooled standard mean deviation (SMD) of 15 studies was 0.559 (95%CI: 0.002-1.196) and the heterogeneity was 96.6%. To reduce the heterogeneity, we chose random effects model and made subgroup analysis according to gestational age at sample testing (<18 weeks and >=18 weeks) and race of included pregnant women. The pooled SMD of gestational age at sample testing >=18 weeks and Chinese were 1.19 (95%CI: 0.63-1.75) and 1.61 (95%CI: 0.82 2.41) and the heterogeneity values (measured by I2) were 93.5% and 76.5%, respectively. CONCLUSIONS: Elevated maternal serum relaxin of later than 18 weeks of gestational age is associated with singleton preterm birth in Chinese women. It might be an important information to prevent singleton preterm delivery in Chinese women. What's already known about this topic? Previous reports reveal that there is a relationship between elevated maternal serum relaxin and preterm birth. However, the included articles contained twin pregnancies and estrogen stimulation, which obviously resulted in higher relaxin concentrations. What does this study add? PMID- 29788817 TI - Inducible nitric oxide inhibitor aminoguanidine, ameliorated oxidative stress, interleukin-6 concentration and improved brain-derived neurotrophic factor in the brain tissues of neonates born from titanium dioxide nanoparticles exposed rats. AB - INTRODUCTION: An interaction between oxidative stress, neuroinflammation, and nitric oxide (NO) has been suggested to have a role neurotoxicity. The aim of current research was to investigate the effect of aminoguanidine (AG) as an inducible NO synthase (iNOS) inhibitor, on brain-derived neurotrophic factor (BDNF), oxidative stress, and interleukin-6 (IL-6) concentrations in the brain tissues of neonates born from the rats exposed to titanium dioxide nanoparticles (TiO2 NPs) during gestation. METHODS: The pregnant rats were grouped into three and received: (1) saline, (2) TiO2 (200 mg/kg, gavage), and (3) TiO2-AG [200 mg/kg intraperitoneal (IP)]. The treatment was started since the second gestation day up to the delivery time. The neonates born from the rats were deeply anesthetized, sacrificed, and the brains were collected for biochemical evaluations. RESULTS: The neonates born from the rats exposed to TiO2 showed a lower BDNF (p < .001) but a higher IL-6 (p < .01) concentrations in their hippocampal tissue. TiO2 exposure also increased malondialdehyde (MDA) (p < .001) and NO metabolites (p < .001), while diminished thiol (p < .001), superoxide (SOD) (p < .001), and catalase (CAT) (p < .001) in all hippocampal, cortical, and cerebellar tissues. Administration of AG improved BDNF (p < .01) but attenuated IL-6 (p < .01) concentrations in the hippocampal tissue. AG also decreased MDA (p < .001) and NO metabolites (p < .01-p < .001), while increased thiol (p < .01-p < .001), SOD (p < .001), and CAT (p < .05-p < .001) in all cerebellar, hippocampal, cortical, and tissues. CONCLUSION: The results of the current research revealed that iNOS inhibitor AG, ameliorated oxidative stress, IL-6 concentration, and improved BDNF in the brain tissues of neonates born from TiO2 NPs exposed rats. PMID- 29788818 TI - A systematic review on the use of deep venous stenting for acute venous thrombosis of the lower limb. AB - Objectives The aim is to evaluate venous stent patency, the development of post thrombotic syndrome, recurrence, quality of life and the optimal post-procedural anticoagulation regimen in the treatment of iliofemoral deep venous thrombosis. Method and results EMBASE and Medline databases were interrogated to identify studies in which acute deep venous thrombosis patients were stented. Twenty-seven studies and 542 patients were identified. Primary, assisted primary and secondary patency rates 12 months after stent placement ranged from 74 to 95, 90 to 95 and 84 to 100%, respectively. The observed post-thrombotic syndrome rate was 14.6%. The incidence of stent re-thrombosis was 8%. In 26% of studies, patients received additional antiplatelet therapy. Quality of life questionnaires employed in 11% of studies, demonstrating an improvement in the chronic venous insufficiency questionnaire (22.67 +/- 3.01 versus 39.34 +/- 6.66). Conclusion Venous stenting appears to be an effective adjunct to early thrombus removal; however, further studies are needed to identify optimal anticoagulant regimen and effect on quality of life. PMID- 29788819 TI - Nurse Spiritual Care: Prevalence and Correlates. AB - Many nurses embrace spiritual care as integral to holistic care. Evidence documenting the frequency of spiritual care provided in acute care settings, however, is sparse and weak. For this cross-sectional, correlational study, data were collected from N = 554 tertiary care nurses using the Nurse Spiritual Care Therapeutics Scale (NSCTS) measuring their self-reported spiritual care with patients/family members over the last 72 to 80 hours at work. While the most frequently endorsed practices centered on presence, listening, and spiritual assessment, the overall NSCTS score remained modest ( M = 37; SD = 12; possible range = 17-85). Several associations were found; 32.4% of the variance in frequency of spiritual care provision was explained by nurse perception that spiritual issues come up often in the work setting, high nurse spirituality score, not working in pediatrics, and having received education about spiritual care. Findings allow for benchmarking of nursing practices that have often been invisible. PMID- 29788820 TI - Injury and infection in dental clinics: Risk factors and prevention. AB - Needlestick and sharp instrument injuries are common in dental practice and present the risk of direct exposure to blood-borne pathogens, including hepatitis B virus. This cross-sectional study was carried out to determine the risk factors of injury and infection in three types of dental clinic in Riyadh, Saudi Arabia. A total of 274 male and 241 female dentists completed a structured questionnaire on demographic factors, compliance with infection control practices, and past exposure to injury and infection hazards. Dentists with more years of professional experience were significantly less likely to report having had an injury in the past (unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.48, 0.27-0.87 and 0.38, 0.16-0.89 for dentists with 10-20 years and for those with over 20 years of experience, respectively). Greater compliance with infection control procedures was associated with significantly fewer reports of previous infection (OR 0.31, 95% CI 0.12-0.84). Experience of occupational safety training was not associated with a lower rate of injury or infection. Greater occupational safety knowledge and compliance with infection control management practices contribute to a reduced risk of injury and infection among dentists. More focused and specialized training on infection control and occupational safety is needed for all practicing dentists and dental students. PMID- 29788821 TI - The Relationship Between Hofstede's Cultural Dimensions, Schwartz's Cultural Values, and Obesity. AB - According to the World Health Organization, obesity is a major public health issue. In 2014, there were more than 600 million obese people around the world. According to the data of the World Health Organization, obesity rates differ among countries. One possible underlying reason of the difference can be culture, more specifically shared cultural values. The strategies and policies regarding obesity were developed; however, the effect of culture is not adequately considered. The aim of the study is to investigate the relationship between obesity rates of countries, Hofstede's cultural dimensions, Schwartz's values, and Gross National Income per capita per country. The data consist of obesity ranking (i.e., the percentage of the population with a body mass index of 30 kg/m2 or higher), Gross National Income per capita for each country, and cultural variables (i.e., Hofstede's cultural dimensions for 54 nations and Schwartz's cultural values for 57 nations). Hierarchical regression analysis results revealed that Gross National Income per capita was not a significantly related obesity at the aggregated level. Among Hofstede's dimensions, individualism and uncertainty avoidance were positively associated with obesity, and long-term orientation was negatively associated with obesity. The relationship between Schwartz's cultural values and obesity was not found to be significant. Findings suggest that Hofstede's cultural dimensions should be considered when developing national level strategies and campaigns to decrease obesity. PMID- 29788822 TI - Paper Spirits and Flower Sacrifices: Hmong Shamans in the 21st Century. AB - INTRODUCTION: Fresno, California, is home to more than 30,000 Hmong. The purpose of this research was to explore the utilization of Hmong shamans 40 years after the first Hmong immigrants arrived in the United States. Hmong shamanism is examined to identify and analyze changes to shamans' practices or patients. METHODS: Using grounded theory, semistructured interviews were conducted with a convenience sample of 20 shamans in their homes. Transcribed data were qualitatively analyzed. RESULTS: Shamans continue to train and practice in this community; utilization by older patients persists while young adult patients have become the fastest-growing group of users. Healing rituals have changed in response to the legalities of animal sacrifice in urban areas and the time demands of work schedules. DISCUSSION: Nurses' awareness that the availability of biomedicine does not preclude the continuing or recurring utilization of traditional healers can facilitate understanding of culturally defined health care needs. PMID- 29788823 TI - Synbiotic supplementation, systemic inflammation, and symptoms of brain disorders in elders: A secondary study from a randomized clinical trial. AB - OBJECTIVES: We aimed to investigate the effect of a symbiotic substance on symptoms of brain disorders and inflammation in the elderly. METHODS: Forty-nine elders, both genders, assigned into two groups: S-group (synbiotic) and P-group (placebo). Evaluations at the beginning and at the end of the experiment: geriatric depressive symptoms scale-15 (GDS-15); mini-mental status examination (MMSE); % of body fat (%fat); serum IL-6, TNF-alpha and IL-10; serum diamine oxidase (DAO), intestinal fatty-acid binding protein (IFABP), and lipopolysaccharide (LPS). RESULTS: Both groups had reduced their %Fat, TNF-alpha, and DAO. The IL-6, GDS-15, and MMSE were increased in both groups. IL-10 was significantly increased only in the S-group, and LPS was significantly reduced only in the P-group. The GDS-15final was negatively explained by DAO, IL-10, TNF alpha, %Fat, being woman, and being allocated in the P-group. The variables that positively explained the GDS-15final were the IL-6, the IFABP, and the LPS. MMSEfinal was positively associated with the IL-10, DAO, being woman, and being allocated in the P-group; and negatively associated with IL-6, TNF-alpha, %Fat, IFABP, and LPS. CONCLUSIONS: We found weak effects of symbiotic on depressive symptoms and more optimistic effects on cognition in apparently healthy elderly. Other studies, with individuals diagnosed with depressive morbidity or cognitive decline, are needed. Registration of Clinical Studies - REBEC (RBR-6qr9xx)]. PMID- 29788824 TI - Activation of AMPK in Human Placental Explants Impairs Mitochondrial Function and Cellular Metabolism. AB - OBJECTIVE: Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor whose phosphorylation increases energy production. We sought to evaluate the placenta-specific effect of AMPK activation on the handling of nutrients required for fetal development. METHODS: Explants were isolated from term placenta of 29 women (pregravid body mass index: 29.1 +/- 9.9 kg/m2) and incubated for 24 hours with 0 to 100 umol/L resveratrol or 0 to 1 mmol/L of 5 aminoimidazole-4-carboxyamide ribonucleoside (AICAR). Following treatment, uptake and metabolism of radiolabeled fatty acids and glucose were measured. Phosphorylation of AMPK was measured by Western blotting. Adenosine diphosphate (ATP) production was assessed using the mitochondrial ToxGlo assay kit. P < .05 was considered statistically significant. RESULTS: Resveratrol and AICAR increased AMPK phosphorylation in human placental explants. Exposure to resveratrol decreased the uptake of polyunsaturated fatty acids, arachidonic acid, and docosahexaenoic acid at 100 umol/L ( P < .0001). Fatty acid oxidation was decreased by 100 umol/L ( P < .05) resveratrol, while esterification was unchanged. Resveratrol decreased glucose uptake at the 50 and 100 umol/L doses ( P < .05). Glycolysis was not significantly affected. AICAR had similar effects, decreasing fatty acid uptake and glycolysis ( P < .05). Production of ATP declined at doses found to decrease nutrient metabolism ( P < .05). CONCLUSIONS: Activation of AMPK in the human placenta leads to global downregulation of metabolism, with mitotoxicity induced at the doses of resveratrol and AICAR used to activate AMPK. Although activation of this pathway has positive metabolic effects on other tissues, in the placenta there is potential for harm, as inadequate placental delivery of critical nutrients may compromise fetal development. PMID- 29788826 TI - Does task-irrelevant colour information create extraneous cognitive load? Evidence from a learning task. AB - Previous studies have shown that task-irrelevant information impedes learning by creating extraneous cognitive load. But still open is whether such intrusion reflects a purely semantic phenomenon or whether it also stands for sheer perceptual interference. Using Cognitive Load Theory as a framework, this study aimed to answer this question by examining whether and how task-irrelevant colour information modifies extraneous cognitive load in relation to a new code-learning paradigm. For this purpose, university students were asked to learn, based on an example, associations between colour-related and colour-unrelated words and digits presented in black or in a mismatched ink colour. Evident costs in learning efficacy were found in learning the associations between words and digits for colour-related, but not for colour-unrelated, word stimuli. This suggests that interference by task-irrelevant information in learning stands for a mere semantic conflict. Implications of the findings for extraneous cognitive load on learning efficacy are discussed. PMID- 29788825 TI - Dioxin-like polychlorinated biphenyls in marine fish from Shandong, China, and human dietary exposure. AB - The occurrence and human dietary exposure of 12 dioxin-like polychlorinated biphenyls (DL-PCBs) in 41 marine fish samples from Shandong Province of China were investigated. The DL-PCB congeners were extracted using automated Soxhlet extraction, purified via a composite column clean-up procedure and analysed by gas chromatography-triple quadrupole mass spectrometry. DL-PCB congeners were found in all analysed samples, with a mean concentration of 0.887 ng/g ww (wet weight). The TEQ concentrations of DL-PCBs in individual fish samples ranged from 0.011 to 9.214 pg WHO TEQ/g ww. The mean dietary intake for all fish species was 36.5 pg TEQ/kg bw/month, which was lower than the provisional tolerable monthly intake of 70 pg TEQ/kg bw/month set by the Joint FAO/WHO Expert Committee on Food Additives. To monitor the trend of DL-PCBs in fish for food safety control, it is necessary to maintain a surveillance programme. PMID- 29788827 TI - Video-based education versus nurse-led education for partner notification in Thai women with sexually transmitted infections: a randomized controlled trial. AB - Health education on sexually transmitted infections (STIs), condom use, and partner notification (PN) is required to increase partner evaluation/treatment (PET) rate. To examine this issue, a randomized controlled trial comparing video based and nurse-led education in women diagnosed with their first STI at the Siriraj Female STI clinic was conducted from March 2015 to March 2017. PN was assessed at two weeks and PET was done at four weeks. Of 330 patients, 225 were included in the analysis (N = 113 and N = 112 for video-based and nurse-led groups, respectively). Each participant reported one partner who needed to be notified. The participants' median age was approximately 30 years old and they had been diagnosed with PID (N = 85), hepatitis B (N = 49), trichomoniasis (N = 45), syphilis (N = 30), and gonorrhea (N = 16). Characteristics were comparable between groups. There was no statistical difference in the PN rates (95.6% vs. 90.2%, p = 0.116), while the PET rate was significantly higher in the nurse-led group (49.6% vs. 67.9%; OR 0.47, 95% CI: 0.27-0.81; p = 0.005). Having endured symptoms for <7 days, being pregnant and detection of STIs during antenatal/pre operative blood tests were positive predictors of PET (OR: 3.34, 95% CI: 1.81 6.14; 18.70, 95% CI: 5.61-62.31; and 22.07, 95% CI: 6.46-75.41, respectively). In conclusion, video-based education is as effective as nurse-led education in terms of PN rate but results in lower PET. PMID- 29788828 TI - Mechanistic kinetic modeling generates system-independent P-glycoprotein mediated transport elementary rate constants for inhibition and, in combination with 3D SIM microscopy, elucidates the importance of microvilli morphology on P glycoprotein mediated efflux activity. AB - INTRODUCTION: In vitro transporter kinetics are typically analyzed by steady state Michaelis-Menten approximations. However, no clear evidence exists that these approximations, applied to multiple transporters in biological membranes, yield system-independent mechanistic parameters needed for reliable in vivo hypothesis generation and testing. Areas covered: The classical mass action model has been developed for P-glycoprotein (P-gp) mediated transport across confluent polarized cell monolayers. Numerical integration of the mass action equations for transport using a stable global optimization program yields fitted elementary rate constants that are system-independent. The efflux active P-gp was defined by the rate at which P-gp delivers drugs to the apical chamber, since as much as 90% of drugs effluxed by P-gp partition back into nearby microvilli prior to reaching the apical chamber. The efflux active P-gp concentration was 10-fold smaller than the total expressed P-gp for Caco-2 cells, due to their microvilli membrane morphology. The mechanistic insights from this analysis are readily extrapolated to P-gp mediated transport in vivo. Expert opinion: In vitro system-independent elementary rate constants for transporters are essential for the generation and validation of robust mechanistic PBPK models. Our modeling approach and programs have broad application potential. They can be used for any drug transporter with minor adaptations. PMID- 29788829 TI - Owner-reported flea treatment measures and skin disease in cats. AB - Objectives The aim of this study was to obtain information regarding the use of flea treatments and owner-reported flea infestation and skin disease. Methods Owners of 1150 cats were recruited into a long-term longitudinal study ('Bristol Cats' study) and asked to complete questionnaires at set time points. Questionnaires 1 and 5 were used and included data collection for kittens aged 2 4 months (T1) and at 2.5 years of age (T2). Owners were asked which brand of flea treatment, if any, was used at each time point. At T2 owners were asked if they had noted signs of skin disease or fleas on their cat within the previous 12 months and if they had sought veterinary attention for the skin disease or fleas. IBM SPSS version 23 was used for statistical analyses. Results Skin disease at T2 was reported by owners of 55/1150 (4.8%; 95% confidence interval [CI] 3.7-6.2) cats. Many owners who reported skin disease (25/55 [45.5%]; 95% CI 32.3-58.7) had not sought veterinary attention. There were 81/1150 (7.0%; 95% CI 5.6-8.5) cats with reported head shaking and/or ear scratching within the past 12 months at T2. The majority of cats (204/286; 71.3%) received prescription flea treatments at both points. Use of non-prescription flea treatment at T2 was more likely to be associated with owner-reported skin disease/flea infestation than those who used prescription flea treatment ( P <0.001). There was a significant association between the reported presence of fleas and reported presence of skin disease at T2 ( P = 0.03). Conclusions and relevance Despite the potential for reverse causality, the association between owner-reported skin disease and/or flea infestation in their cats and the use of non-prescription flea treatment was as expected. Use of flea treatments and, in particular, the type of ectoparasite control used (prescription or non-prescription) should be carefully assessed when managing cats with skin disease. PMID- 29788830 TI - Response, disease-free interval and overall survival of cats with nasal planum squamous cell carcinoma treated with a fractionated vs a single-dose protocol of strontium plesiotherapy. AB - Objectives The main aim of the study was to establish response, disease-free interval (DFI) and overall survival of cats with nasal planum squamous cell carcinoma (SCC) treated with Sr90 plesiotherapy. A secondary aim was to determine whether a fractionated protocol is more effective than a single-dose protocol in terms of response, DFI and overall survival. The third aim was to evaluate whether we can identify prognostic factors that influence overall survival. Methods This was a retrospective study that included cats with a diagnosis of nasal planum SCC treated with Sr90 plesiotherapy at a single institution. Results Seventy-four cats were included in the study. Thirty-two were treated with a fractionated protocol and 42 with a single-dose treatment. Sr90 plesiotherapy was able to induce complete response in 74% of cats with nasal planum SCC. The median DFI was 780 days (95% confidence interval [CI] 383-1177), with 17% of cats experiencing local recurrence. The overall survival for all cats was 1039 days (95% CI 55-1528). The DFI of cats treated with the fractionated Sr90 was significantly longer compared with the single-dose treatment, whereas response and overall survival were not statistically different. Other prognostic factors that influenced the overall survival were early-stage disease, absence of concurrent problems and complete response to the treatment. Acute and long-term toxicity associated with the treatment were minimal and the aesthetic outcome was pleasing in almost all cases. Conclusions and relevance Strontium plesiotherapy is a safe and effective treatment of nasal planum SCC in cats. PMID- 29788831 TI - Lumbosacral transitional vertebrae in cats and its relationship to lumbosacral vertebral canal stenosis. AB - Objectives Although a clear relationship has been demonstrated between the presence of lumbosacral transitional vertebrae and the development of lumbosacral stenosis in dogs, this relationship has not been evaluated in cats. The aim of this study was to investigate the relationship between the presence of lumbosacral transitional vertebrae and lumbosacral stenosis in cats. Methods The medical records and diagnostic imaging studies of 13 cats diagnosed with lumbosacral stenosis were retrospectively reviewed for lumbosacral abnormalities and compared with findings of 405 cats that underwent CT for reasons unrelated to spinal disease. Results Clinical signs associated with lumbosacral stenosis included lumbosacral pain, low tail carriage, difficulty jumping, and urinary or faecal incontinence. Neurological signs included proprioceptive deficits, ambulatory paraparesis, pelvic limb ataxia, reduced spinal reflexes and reduced perianal reflex. Duration of clinical signs ranged from 1 day to 10 months (mean 3 months). Of the 13 cats with lumbosacral stenosis, seven (53.8%) were diagnosed with lumbosacral transitional vertebrae. In the control population of 405 cats, 24 (5.9%) were diagnosed with lumbosacral transitional vertebrae. Results indicated that lumbosacral transitional vertebrae were significantly ( P <0.0001) more prevalent in cats with lumbosacral stenosis compared with the control feline population (odds ratio 18.52, 95% confidence interval 6.1-62.1). Development of clinical signs of lumbosacral stenosis in cats with lumbosacral transitional vertebrae (mean 10.8 years) was not significantly different from that of cats without lumbosacral transitional vertebrae (mean 12.7 years). Likewise, there was no significant influence of breed ( P >0.99) or sex ( P = 0.29) on the occurrence of lumbosacral transitional vertebrae. Conclusions and relevance Despite lumbosacral stenosis being a rare spinal condition in cats, lumbosacral transitional vertebrae can be considered a risk factor for its development. PMID- 29788832 TI - Feline injection site sarcoma: immunohistochemical characteristics. AB - Objectives Feline injection site sarcoma (FISS) is a rapid growing locally aggressive tumor with a low metastatic rate. Its histologic features are clearly defined, but there are few studies regarding its immunohistochemical characteristics. The present study investigated the immunohistochemical characteristics of 21 cases of FISS. Methods FISSs from 12 male and nine female cats, 20 mixed-breed and one Siamese, were included in the study. After histopathological diagnosis, additional histologic sections were immunostained for vimentin, cytokeratin, desmin, S100 protein, viral feline leukemia virus (FeLV) particles, cyclooxygenase 2 (COX-2) and c-KIT. Positive and negative controls were adopted accordingly. Immunostainings were classified as positive and/or negative according to the number of positive cells from a total of 1000 cells per tumor section. Results Histopathologic diagnosis of the tumors revealed 18 (85.7%) fibrosarcomas and three (14.3%) other sarcomas; four fibrosarcomas (22.2%) were grade III, five (27.8%) were grade II and nine (50.0%) were grade I. Two sarcomas were grade III and one was grade II. Seventeen (81%) tumors were negative for desmin. All samples were positive for vimentin. Twenty tumors (95.2%) were positive for S-100 protein. Positivity for c-KIT was observed in four (19%) samples; COX-2 was positive in 13 (61.9%) and FeLV viral particles were positive in nine (42.9%) FISSs. Conclusions and relevance Immunohistochemical findings of FISSs revealed positive immunostainings for desmin, vimentin, S-100 protein, c-KIT, COX-2 and FeLV viral particles. PMID- 29788835 TI - A symbiosis and a beginning. PMID- 29788834 TI - Echocardiography in extracorporeal life support: A key player in procedural guidance, tailoring and monitoring. AB - Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here. PMID- 29788837 TI - EuroELSO 2018 Abstracts. PMID- 29788836 TI - Intracranial hemorrhage in adults on ECMO. AB - RATIONALE: Extracorporeal membrane oxygenation (ECMO) use has exploded over the last decade. However, it remains invasive and associated with significant complications, including tamponade, infection, thrombosis, gas embolism and bleeding. The most dreaded complication is intracranial hemorrhage (ICH). In this article, we review the literature on the incidence, diagnosis, risk factors, pathophysiology, prognosis, prevention and management of ICH in adults on ECMO. MAIN FINDINGS: We found a high incidence of ICH in the literature with a poor prognosis. Important risk factors included pre-ECMO cardiac arrest, sepsis, influenza, renal failure, renal replacement therapy, hemolysis and thrombocytopenia. The optimal anticoagulation strategy is still uncertain. As platelet dysfunction and depletion appear to play an important role in the pathogenesis of ICH in patients on ECMO, a liberal platelet transfusion strategy may be advised. Prompt computed tomography (CT) diagnosis is of great importance as interventions to limit hematoma expansion and secondary neurological injury are most effective if instituted early. Transporting patients to the radiology department can be performed safely while on ECMO. A strategy combining screening CT on admission with a heparin-free period of extracorporeal support was demonstrated to be safe in VV-ECMO patients and resulted in a better prognosis compared to similar cohorts in the literature. CONCLUSION: Despite major technological improvements and all the experience gained in adults, ECMO remains associated with a high incidence of ICH. There are still wide gaps in our understanding of the disease. Optimal management strategies that minimize the risk of ICH and improve prognosis need to be further studied. PMID- 29788838 TI - In vitro and in vivo assessment of oxygenator blood volume for the prediction of clot formation in an ECMO circuit (theory and validation). AB - INTRODUCTION: Clotting is one of the major causes of mortality and morbidity during extracorporeal membrane oxygenation (ECMO). A large meta-analysis study suggests that 29% of patients require the oxygenator to be replaced during ECMO. As clots usually form in the oxygenator, the oxygenator blood volume (OXBV) decreases over time. The currently used pressure gradient as a predicator of clot formation is unreliable. OBJECTIVE: The aim of this study was to develop and validate ultrasound dilution technology in a quantitative assessment of clotting, using measurements of OXBV. METHODS: OXBV was measured using the ELSA monitor (Transonic Systems Inc., Ithaca, NY, USA) from the transit time of a saline bolus passing through the oxygenator as recorded by a sensor placed after the oxygenator. The accuracy and reproducibility (coefficient of variation [CV]) of OXBV measurement and its independence from ECMO flow was assessed in vitro in lambs and from a clinical data archive. RESULTS: The in vitro accuracy compared with volumetric measurements of OXBV of 22-134 ml at flows of 300-700 ml/min was 0.8+/-6.6%. For an OXBV of 355 ml at flows of 1020-7000 ml/min, accuracy was 0.4+/-1.6%. In 88 animal OXBV measurements, the CV was 1.49+/-1.12%. For an OXBV of 153 (range 42-387 ml), clinical measurements at flow ranged from 210-5960 ml/min, with a CV of 3.20+/-2.44 %. CONCLUSION: Dilution technology has the ability to accurately and reproducibly assess the clotting process in the oxygenator. Larger studies are needed to establish guidelines for the prediction of imminent clotting and may help to avoid unnecessary circuit changes. PMID- 29788839 TI - Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation. AB - INTRODUCTION: The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants. METHODS: The aim of the study was to evaluate the individual pharmacokinetics (PK) of phenobarbital and the effect of PK covariates in neonates and infants undergoing ECMO. Sixteen patients (7 neonates, 9 infants) treated with phenobarbital during ECMO (centrifugal-flow pump circuits) were enrolled in the PK study. Phenobarbital serum concentrations were measured using a fluorescence polarization immunoassay. Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model. RESULTS: The mean (SD) Vd and CL values in neonates were 0.46 (0.24) L/kg and 8.0 (4.5) mL/h/kg, respectively. Respective values in infants were 0.56 (0.23) L/kg and 8.5 (3.1) mL/h/kg. PK parameters in neonates and infants were not significantly different. We observed high inter-individual variability in PK parameters (coefficients of variation [CV] were 52% and 53% for CL and Vd, respectively). Doses were adjusted based on therapeutic drug monitoring (TDM) in 87.5% patients. Only 50% of the first measured phenobarbital serum concentrations in each patient were within the therapeutic range of 10-40 mg/L, in comparison with 88.6% concentration measured after TDM implementation. Linear regression models showed that both Vd and CL are significantly related with body weight (BW) and length. Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively. CONCLUSIONS: Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO. PMID- 29788840 TI - New, optimized, dual-lumen cannula for veno-venous ECMO. AB - OBJECTIVE: The present study was designed to assess in vivo a new, optimized, virtually wall-less, dual-lumen, bi-caval cannula for veno-venous ECMO in comparison to a commercially available cannula. METHODS: Veno-venous extracorporeal membrane oxygenation (ECMO) was carried out in a bovine study (n=5, bodyweight 75+/-5kg). Following systemic heparinization, ECMO was established in a trans-jugular fashion through a calibrated 23F orifice, using a new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula (Smartcanula LLC, Lausanne, Switzerland) versus a commercially available 23F bi caval, dual-lumen control cannula (Avalon Elite(r), Maquet, Rastatt, Germany) in a veno-venous ECMO setup. Veno-venous ECMO was initiated at 500 revolutions per minute (RPM) and increased by incremental steps of 500 RPM up to 2500 RPM. Catheter outlet pressure, catheter inlet pressure, oxygen saturation and pump flow were recorded at each stage. RESULTS: Mean flow accounted for 0.37+/-0.04 L/min for wall-less versus 0.29+/- 0.07 L/min for control at 500 RPM, 0.97+/-0.12 versus 0.67+/-0.06 at 1000 RPM, 1.60+/-0.14 versus 1.16+/-0.08 at 1500 RPM, 2.31+/-0.13 versus 1.52+/-0.13 for 2000 RPM and 3.02+/-0.5 versus 2.11+/-0.18 (p<0.004). The mean venous suction required was 19+/-8 mmHg for wall-less versus 20+/-3 mmHg for control at 500 RPM, 7+/-3 versus 9+/-4 for 1000 RPM, -11+/-10 versus -12+/-8 at 1500 RPM, -39+/-15 versus -49+/-10 for 2000 RPM and -60+/-28 versus -94+/-7 for 2500 RPM. The mean venous injection pressure accounted for 29+/-7 mmHg for wall-less versus 27+/-5 mmHg for control at 500 RPM, 50+/-6 versus 61+/-7 at 1000 RPM, 89+/-10 versus 99+/-17 for 1500 RPM, 142+/-14 versus 161+/-9 at 2000 RPM and 211+/-41 versus 252 +/-3 for 2500 RPM. CONCLUSION: Compared to the commercially available control cannula, the new, optimized, virtually wall-less, dual-lumen, bi-caval 24F cannula allows for significantly higher blood flows, requires less suction and results in lower injection pressures in vivo. PMID- 29788841 TI - Heparin-induced thrombocytopenia complicating extracorporeal membrane oxygenation support in pediatric patients: review of the literature and alternative anticoagulants. AB - Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated complication of unfractionated heparin (UFH) and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5-10 days after initial heparin exposure, detection of platelet-activating anti-platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The following article reviews the current knowledge in pediatric HIT, especially in ECMO patients, and the alternative anticoagulation options in the presence of HIT. PMID- 29788842 TI - Veno-arterio-venous ECMO for septic cardiomyopathy: a single-centre experience. AB - INTRODUCTION: The role of extracorporeal support for patients with septic shock remains unclear. METHODS: We conducted a retrospective analysis of our single centre experience with veno-arterio-venous extracorporeal membrane oxygenation (VAV ECMO) in adult patients with severe respiratory failure and septic cardiomyopathy. Clinical data was extracted from electronic medical records including a dedicated ECMO referral and follow-up database. RESULTS: Twelve patients were commenced on VAV ECMO for septic cardiomyopathy for a median of four days (IQR 3.0 to 5.3) between 01/2014 and 12/2017. Five patients (41.7%) had a cardiac arrest prior to initiation of ECMO support. At baseline, median left ventricular ejection fraction was 16.25% (IQR 13.13 to 17.5) and median PaO2/FiO2 ratio was 9 kPa (IQR 6.5 to 12.0) [67.50 mmHg (IQR 48.75 to 90.00)]. The survival rate to hospital discharge for VAV ECMO was 75% in this cohort. None of the surviving patients died within the follow-up period (median six month). CONCLUSION: VAV ECMO is a feasible rescue strategy for a small proportion of patients with combined respiratory and cardiac failure secondary to septic shock with septic cardiomyopathy. We provide a detailed report of our experience with this technique. Further research is required comparing the different extracorporeal strategies directly to conventional resuscitation and against each other. PMID- 29788843 TI - Effect of pump type on outcomes in neonates with congenital diaphragmatic hernia requiring ECMO. AB - PURPOSE: With the exception of neonatal respiratory failure, most centers are now using centrifugal over roller-type pumps for the delivery of extracorporeal membrane oxygenation (ECMO). Evidence supporting the use of centrifugal pumps specifically in infants with congenital diaphragmatic hernia (CDH) remains lacking. We hypothesized that the use of centrifugal pumps in infants with CDH would not affect mortality or rates of severe neurologic injury (SNI). METHODS: Infants with CDH were identified within the ELSO registry (2000-2016). Patients were then divided into those undergoing ECMO with rollertype pumps or centrifugal pumps. Patients were matched based on propensity score (PS) for the ECMO pump type based on pre-ECMO covariates. This was done for all infants and separately for each ECMO mode, venovenous (VV) and venoarterial (VA) ECMO. RESULTS: We identified 4,367 infants who were treated with either roller or centrifugal pumps from 2000-2016. There was no difference in mortality or SNI between the two pump types in any of the groups (all infants, VA-ECMO infants, VV-ECMO infants). However, there was at least a six-fold increase in the odds of hemolysis for centrifugal pumps in all groups: all infants (odds ratio [OR] 6.99, p<0.001), VA ECMO infants (OR 8.11, p<0.001 and VV-ECMO infants (OR 9.66, p<0.001). CONCLUSION: For neonates with CDH requiring ECMO, there is no survival advantage or difference in severe neurologic injury between those receiving roller or centrifugal pump ECMO. However, there is a significant increase in red blood cell hemolysis associated with centrifugal ECMO support. PMID- 29788844 TI - The first five years of neonatal and pediatric transports on extracorporeal membrane oxygenation in the center and south of Italy: The pediatric branch of the Italian "Rete Respira" network. AB - INTRODUCTION: Neonatal and pediatric ECMO is a high-risk procedure that should be performed only in expert centers. Children who are eligible for ECMO and are managed in hospitals without ECMO capabilities should be referred to the closest ECMO center before the severity of illness precludes safe conventional transport. When the clinical situation precludes safe conventional transport, ECMO should be provided on site with the patient transported on ECMO. METHODS: We retrospectively reviewed our institutional database of all ECMO transports for neonatal and pediatric respiratory failure from February 2013 to February 2018. RESULTS: Over the last 5 years, we provided 24 transports covering all requests from the center and south of Italy except for the islands. Of these transports, 20 were performed on ECMO and 4 without ECMO. No patient died during transportation. Five complications were reported only during the ECMO transports, and all of these were managed without compromising the patient's safety. The preferred modes of transport were by ambulance (70%) and ambulance transported into the fixed wing aircraft (30%) for longer national distances. The survival to hospital discharge of the patients transported with ECMO was 75% among the neonatal transports and 83.3% among the pediatric transports. The survival to hospital discharge of the four patients transported without ECMO was 100% for both neonates and children. CONCLUSIONS: Neonatal and pediatric ECMO transports can be safely performed with a dedicated team that maintains stringent adherence to well-designed management protocols. PMID- 29788845 TI - Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study. AB - INTRODUCTION: Relationship between regional tissue oxygenation (rSO2) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO2, microcirculation and systemic hemodynamic parameters in a porcine model of CA. METHODS: Ventricular fibrillation was induced in 24 female pigs (50+/-3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. RESULTS: Brain and peripheral rSO2 showed a gradual decrease during CA and only an increase of brain rSO2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). CONCLUSIONS: Our experimental study confirmed that monitoring brain and peripheral rSO2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO2 reflects the CPR efforts and might be used as a potential quality indicator for CPR. PMID- 29788846 TI - [Patient- vs Physician-Reported Implementation of and Compliance to Anti Osteoporotic Medication One Year after Sustained Fragility Fracture]. AB - Patient- vs Physician-Reported Implementation of and Compliance to Anti Osteoporotic Medication One Year after Sustained Fragility Fracture Abstract. We were interested why therapy recommendations made by specialists are often not followed by general practitioners (GPs) and patients. We evaluated systematic questionnaires comparing both, patient and GP statements (n = 151 each) with regard to the implementation of and compliance to specific therapy recommended by an osteologic specialist one year after an osteoporotic fracture. In 53 % GPs prescribed antiosteoporotic drugs, more often if the indication for treatment was less aggressive (p <0.001). Once prescribed, in 94 % of cases the GPs' medication followed the specialists' recommendations. 74 % of patients followed their GP's prescription. Patients most often stated a missing prescription as the reason for not taking drugs (39 %), whereas GPs cited a missing interest of their patients (44 %). The observed discrepancies call for a melioration in the communication between all parties involved. PMID- 29788847 TI - ? PMID- 29788849 TI - ? PMID- 29788848 TI - [Sports in Patients with Heart Disease: What Should Be Recommended?] AB - Sports in Patients with Heart Disease: What Should Be Recommended? Abstract. Sports is recommended in the European guidelines for the prevention and initial treatment of many cardiovascular diseases as well as the metabolic syndrome. However, the individually recommended intensity and duration of physical activity that unfolds the maximal protective effects in terms of prevention, largely differs. Indeed, a J-curve relationship with regard to exercise training has been postulated, with the assumption that too much sports is equally harmful or potentially even more harmful than too little sports. In this review, we try to answer the question of how much and which sports is optimal for cardiac patients. PMID- 29788850 TI - ? PMID- 29788851 TI - [Micturition Complaints in Men: One Symptom, Multiple Causes]. AB - Micturition Complaints in Men: One Symptom, Multiple Causes Abstract. Micturition complaints in male patients are a common problem in the general practice. The complaints are summarized as lower urinary tract symptoms (LUTS) and are often an expression of prostate enlargement and the resulting bladder outlet -obstruction. Differential diagnosis has to exclude prostate-related LUTS. Basic diagnostics are performed by means of detailed physical history, Combur test and ultrasound. The most common diagnoses can already be made at this point and therapy can be initiated. If -secondary changes of the urinary tract (dilated upper urinary tract, bladder diverticulum formation) already show, specialist -assessment and operative therapy are indicated. PMID- 29788852 TI - ? PMID- 29788853 TI - [CME Answers: "Periinterventional Management of Direct Oral Anticoagulants - Balancing Benefits and Risks", Praxis No. 9-10]. PMID- 29788855 TI - [CME Laboratory 54: Inflammation Markers]. PMID- 29788854 TI - [Myocardial Clefts - Incidental Findings in Parainfectious Myocarditis]. AB - Myocardial Clefts - Incidental Findings in Parainfectious Myocarditis Abstract. We report a 23-year-old woman with parainfectious myocarditis due to gastroenteritis. A transthoracic echocardio-graphy revealed a recess in the left inferobasal ventricle. For further investigation, cardiac magnetic resonance imaging was initiated, which revealed a myocardial cleft, a harmless structural variation of the heart. Cardiac magnetic resonance is a non-invasive imaging technique with a high spatial and temporal resolution that enables a precise depiction of the cardiac anatomy and therefore allows for a differentiation between normal and pathological structural variations of the heart. PMID- 29788856 TI - [CME Rheumatology 16: Tennis Elbow - Epicondylitis]. PMID- 29788857 TI - [CME: Rabies Update: Symptoms, Diagnostics and Therapy]. AB - Rabies is one of the oldest known infectious diseases and certainly one of the most feared because of its impressive course. Despite continuous improvement in medical treatment, the disease continues to be almost always fatal after onset of symptoms. Due to urbanization, rabies has lately somewhat disappeared from the public focus in Central Europe. Because of the remaining high number of fatal cases due to rabies infection worldwide and the persistent risk of contagion on holiday or within Switzerland, e.g. due to illegal import of infected animals, the disease is becoming a frequent topic in the media again. PMID- 29788858 TI - Capacity of Objective Measures of Physical Activity to Predict Brazilian Children's Low Motor Proficiency. AB - This study analyzed the associations between physical activity (PA) and motor proficiency (MP) to determine what level of moderate PA might help avoid low MP in 8-10-year-old Brazilian children. We assessed MP of 98 children using the Bruininks-Oseretsky Motor Proficiency, Second Edition Short Form (BOT-2 SF), and we assessed PA using the GT3X + accelerometer. We analyzed data using means, standard deviations, frequency distribution, spearman correlation coefficients, Mann-Whitney U test, and the Receiver Operating Characteristics curve. There was a difference between groups of children with adequate or better versus low MP in minutes/day of moderate PA (defined as 2,296-4,011 accelerometer counts/minute; U = 666.0, p = .045) such that those with less time engaged in moderate PA had lower MP scores than peers with adequate MP. There was also a positive correlation between moderate PA and the strength and agility MP domain ( rs = .226; p = .025). In addition, minutes/day of moderate PA less than or equal to 142.56 minutes showed predictive capacity for low MP (area under the curve = 0.635; p = .027). Thus, objective measures of PA were able to predict low MP in 8 10-year-old Brazilian children, with an approximate guideline of about 2.5 hours per day of moderate PA needed to protect against low MP. PMID- 29788860 TI - Comparative Effects of Auditory Electromyographic Biofeedback for Participants Who Are Blind and Sighted. AB - This study examined differences in auditory electromyographic biofeedback (AEB) effects between participants who were sighted and blind. Past research makes clear that AEB is effective for people who are blind, particularly because of their reported superiority in auditory processing, but no study has directly compared AEB efficacy between participants who are sighted and blind. A total of 11 participants who were sighted and 10 who were blind performed a motor task requiring 20 nonfatiguing muscle contractions at 20% maximal voluntary contraction (MVC) with or without AEB. AEB reduced the error (calculated as the absolute difference of two consecutive contractions) among both participant groups, and the error for the group without biofeedback was greater for the participants who were blind than that for the sighted participants (5.20% +/- 2.05% MVC and 3.30% +/- 1.26% MVC, respectively; p < .05). This finding was consistent with subjective rating data, also indicating a trend toward greater difficulty for participants who were blind when performing without biofeedback. Moreover, the AEB/no biofeedback condition showed fewer errors for the participants who were blind than for the participants who were sighted during the last part of the task ( p = .036), indicating that participants who were blind were better at maintaining the AEB effect. These data suggest that the poor motor performance of participants who were blind was greatly improved with AEB, suggesting important applications of AEB for assistive technologies, adapted sports, and activities of daily living. PMID- 29788862 TI - Cigarette Smoking Cessation Involving the 5-A Framework. AB - Occupational health nurses (OHNs) need to have adequate knowledge and skills to manage and educate individuals about smoking cessation. PMID- 29788859 TI - Female Judo Athletes' Physical Test Performances Are Unrelated to Technical Tactical Competition Skills. AB - This study analyzed the relationship between generic and judo-specific physical test performances and technical-tactical competition performances among 19 female judo athletes. Participant data were gathered in two stages: (a) physical tests countermovement jump (CMJ), handgrip strength, Special Judo Fitness Test and Judogi Grip Strength Test; and (b) match performances recorded for technical tactical analysis. Pearson's linear correlation and multiple linear regression analysis showed no significant correlations between any technical-tactical parameter and judo-specific physical tests. However, the number of attacks during matches was significantly positively correlated with countermovement jump height (CMJJH; r = 0.69, p = .002), peak power output (CMJPPO; r = 0.53, p = .002), and peak velocity (CMJPV; r = 0.62, p = .001). Effective time during matches was significantly correlated with all CMJ parameters (except maximum force; r = 0.65 0.76, p <= .01) and with right hand grip strength ( r = 0.48, p = .037). Match effectiveness was correlated with CMJPPO ( r = -0.67, p = .001), mean power output (CMJMPO; r = -0.54, p = .017), and CMJPV ( r = -0.54, p = .004). The explained power of variance was low for all variables at 45-54%. We conclude that judo-specific performance tests do not seem to be related to female judo athletes' technical-tactical skills in official competition, though athletes with higher lower limb muscle power and higher handgrip strength showed higher time effectiveness during matches. PMID- 29788863 TI - Erratum for Selenium and Selenoproteins: An Overview on Different Biological Systems. AB - Current Protein and Peptide Science, 2014, 15(6): 598-607. Selenium and Selenoproteins: An Overview on Different Biological Systems Erika Mangiapane*, Alessandro Pessione and Enrica Pessione Regrettably authors of the article entitled "Selenium and Selenoproteins: An Overview on Different Biological Systems" declare that due to a oversight at there end, in the original article, there is an error in the reported name of the bacterial strain. The bacterial strain was reported as Lactobacillus reuteri Lb2 (DSM 16143) but it should have been reported as Lactobacillus reuteri Lb26 (DSM 16341). Therefore, any instances of Lb2 (DSM 16143) should be replaced with Lb26 (DSM 16341). The experimental work was conducted on the strain Lactobacillus reuteri Lb26 (DSM 16341), formerly classified as Lactobacillus buchneri Lb26 (DSM 16341). Unfortunately the strain provided was mislabeled as Lactobacillus reuteri Lb2 (DSM 16143), which does not possess any of the specific traits published. The results of the research were unaffected by this labelling issue. The last reference should read: Lamberti, C.; Mangiapane, E.; Pessione, A.; Mazzoli, R.; Giunta, C.; Pessione, E. Proteomic characterization of a seleniummetabolizing probiotic Lactobacillus reuteri Lb26 (DSM 16341) for nutraceutical applications. Proteomics, 2011, 11(11), 2212-2221. PMID- 29788864 TI - Editorial: Protein and Sarcopenia: Experimental Data and Clinical Evidence. PMID- 29788865 TI - Editorial: Head and Neck Cancer: Recent Findings and New Targets. PMID- 29788866 TI - Editorial: Integrative Approach to Manage Neurological Disorders. PMID- 29788868 TI - Contribution of spinal cord oligodendrocytes to neuroinflammatory diseases and pain. AB - BACKGROUND: Neuroinflammatory diseases that affect spinal cord or associated spinal nerves represent challenging conditions for management in current medicine because of their complex pathology, poor prognosis, and high morbidity, which strikingly reduces the quality of life of patients. In this sense, a better understanding of the cellular and molecular mechanisms of spinal cord neuroinflammation might contribute to the development of novel therapies. Oligodendrocytes have unique and vital biological properties in central nervous system (CNS) homeostasis and physiology. A growing body of experimental evidence demonstrates that these glial cells are involved in the pathophysiological mechanisms underlying many chronic, neurodegenerative, and incapacitating CNS disorders. These cells also have important implications for the development and maintenance of neural plasticity and chronic pain states. On the other hand, evidence indicates that oligodendrocytes and their products may act in favor of CNS promoting beneficial effects orchestrating CNS tissue repair after injury. OBJECTIVE: The present review aims to explore the multi-faceted actions of spinal cord oligodendrocyte progenitors cells (OPCs) and mature oligodendrocytes in CNS inflammation and pathology, addressing their roles in experimental and clinical settings. A major focus was given to spinal cord amyotrophic lateral sclerosis, multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), traumatic injury and pain processing. METHODS: This review analyses and discusses published original research articles regarding the role of OPCs/oligodendrocytes in spinal cord inflammation and pain processing. RESULTS AND CONCLUSION: Findings from a number of clinical and experimental paradigms suggest spinal cord OPCs/oligodendrocytes are a potential therapeutic target for the control of neuroinflammation. PMID- 29788869 TI - Advances in the tyrosinase inhibitors from plant source. AB - Tyrosinase is a multifunctional copper-containing oxidase which catalyses the oxidation of tyrosine to produce melanin. The alteration in melanin biosynthesis occurs in many diseases. The pigment has a protecting role against skin photo carcinogenesis, but anomalous melanin pigmentation is an aesthetic problem in human beings. Moreover, the formation of neuromelanin in human brain could contribute to the neurodegeneration associated with Parkinson's disease. Finally, tyrosinase is also responsible of undesired browning in fruits and vegetables. These topics encouraged the search for new inhibitors of this enzyme for pharmaceutical, cosmetic and foods industries. This review is to report recent trends in the discovery of tyrosinase inhibitors from plant sources, to provide a rationale for the continued study of natural tyrosinase inhibitors, and to recognise the potential therapeutic rewards associated with the identification of these agents. PMID- 29788870 TI - Small molecules as drugs to upregulate metastasis suppressors in cancer cells. AB - It is well-recognized that the majority of cancer-related deaths are attributed to metastasis, which can arise from virtually any type of tumor. Metastasis is a complex multistep process wherein cancer cells must break away from the primary tumor, intravasate into the circulatory or lymphatic systems, extravasate, proliferate and eventually colonize secondary sites. Since these molecular processes involve the coordinated actions of numerous proteins, targeted disruptions of key players along these pathways represent possible therapeutic interventions to impede metastasis formation and reduce cancer mortality. A diverse group of proteins with demonstrated ability to inhibit metastatic colonization have been identified and they are collectively known as metastasis suppressors. Given that the metastasis suppressors are often down regulated in tumors, drug-induced re-expression or upregulation of these proteins represents a promising approach to limit metastasis. Indeed, over 40 compounds are known to exhibit efficacy in upregulating the expression of metastasis suppressors via transcriptional or post-transcriptional mechanisms, and the most promising ones are being evaluated for their translational potentials. These small molecules range from natural products to drugs in clinical use and they apparently target different molecular pathways, reflecting the diverse nature of the metastasis suppressors. In this review, we provide an overview of the different classes of compounds known to possess the ability to upregulate one or more metastasis suppressors, with an emphasis on their mechanisms of action and therapeutic potentials. PMID- 29788871 TI - Biologics for the treatment of Juvenile Idiopathic Arthritis. AB - Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate specific mechanisms of the immune systems, such as TNF-alpha, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidences regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized. PMID- 29788872 TI - Recent Advances in Magnetic Nanoparticle-based Molecular Probes for Hepatocellular Carcinoma Diagnosis and Therapy. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, leading to the second most likely cause of cancer-related deaths. Medical imaging is crucial in clinic for HCC screening and diagnosis. Due to the relatively high special resolution and excellent sensitivity, magnetic resonance imaging (MRI) by using magnetic nanoparticle-based contrast agents has been used so far in HCC imaging and staging, demonstrating great potential and promising in vivo applications. This review focuses on the use of different magnetic nanoparticles for construction of HCC nanoprobes for MR imaging and theranostic purpose. PMID- 29788873 TI - One Molecule, Many Targets and Numerous Effects: The Pleiotropy of Curcumin Lies in its Chemical Structure. AB - Curcumin quite possibly represents one of the most diverse therapeutic agents yet isolated from natural sources. Therapeutic benefits of this extraordinary natural compound have been demonstrated during treatment of a variety of diseases, including cancer, inflammatory processes, immunological disorders, Diabetes, and oxidative stress often associated with hyperlipidemia. Due to its unique molecular chemical structure and functional groups, curcumin may bind with and subsequently either inhibit or activate a variety of endogenous biomolecules, including enzymes, receptors, signaling molecules, metals, transcription factors, and even certain proteins located in cell membranes. In fact, curcumin exerts pharmacologically useful effects through non-covalent interactions with biomolecules. With so many varied biological targets, curcumin (a polyphenol) elicits numerous pleiotropic effects, which is therapeutically advantageous owing to the fact that many pathological disease states involve more than one signaling pathway, receptor, protein/enzyme, or gene. In this paper, we will discuss the underlying mechanisms responsible for the chemical interaction of curcumin with selected classes of biomolecules, rather than attempt to provide an exhaustive list of each and every biomolecule with which curcumin may chemically interact. PMID- 29788874 TI - Hydroxytyrosol: Emerging Trends in Potential Therapeutic Applications. AB - Hydroxytyrosol (HT) and its derivatives represent the minor components of Virgin Olive Oil (VOO) that are of great interest for their pharmacological properties and among the most widely researched natural antioxidant compounds. In this review, the occurrence and metabolic fate of HT and its precursors are presented prior to discussing its beneficial effects on health. Bioavailability studies show that the metabolites detected in plasma depend on the model used (animal or human), the HT source (simple molecule or complex precursors) and the dose administered. However, in all cases HT sulphate appears to be the most ubiquitous metabolite in biofluids and it seems probable that it is responsible to a great extent for HT biological effects. Epidemiological evidence of HT and its derivatives against such lifestyle-associated pathologies as cancer, cardiovascular and neurodegenerative diseases is reviewed together with the newest perspectives on the mechanisms of action based on in-vitro and animal studies. According to the reviewed data, HT and its precursors could have the potential clinical use in cardiovascular diseases; more epidemiological data is needed to demonstrate their neurodegenerative diseases and cancer prevention. PMID- 29788875 TI - Anti-Cancer and Radio-Sensitizing Effects of Curcumin in Nasopharyngeal Carcinoma. AB - Nasopharyngeal Cancer (NPC) is a rare type of head and neck cancer that is mainly treated by radiotherapy, but sometimes it is radioresistant. Curcumin is a polyphenolic natural product with established anticancer effects in various human cancers. Recent studies have shown that curcumin has therapeutic and radiosensitizing effects on NPC cells. In fact, it has been found that curcumin can sensitize NPC cells to radiation through different mechanisms, including modulation of ROS generation, Jab1/CSN5 and non-coding RNAs. As curcumin is safe and lacks systemic toxic effects in humans, it may be considered as a potential candidate to enhance the therapeutic effects of radiation and potentiate the efficacy of chemotherapy in the context of combination regimens. PMID- 29788876 TI - Exploiting Significance of Physical Exercise in Prevention of Gastrointestinal Disorders. AB - BACKGROUND: Physical activity can be involved in the prevention of gastrointestinal (GI)-tract diseases, however, the results regarding the volume and the intensity of exercise considered as beneficial for protection of gastrointestinal organs are conflicting. AIMS AND METHODS: The main objective of this review is to provide a comprehensive and updated overview on the beneficial and harmful effects of physical activity on the gastrointestinal tract. We attempted to discuss recent evidence regarding the association between different modes and intensity levels of exercise and physiological functions of the gut and gut pathology. RESULTS: The regular, moderate exercise can exert a beneficial effect on GI-tract disorders such as reflux esophagitis, peptic ulcers, cholelithiasis, constipation and Inflammatory Bowel Disease (IBD) leading to the attenuation of the symptoms. This voluntary exercise has been shown to reduce the risk of colorectal cancer. On the other hand, there is considerable evidence that the high-intensity training or prolonged endurance training can exert a negative influence on GI-tract resulting in the exacerbation of symptoms. CONCLUSION: Physical activity can exhibit a beneficial effect on a variety of gastrointestinal diseases, however, this effect depends upon the exercise mode, duration and intensity. The accumulated evidence indicate that management of gastrointestinal problems and their relief by the exercise seems to be complicated and require adjustments of physical activity training, dietary measures and medical monitoring of symptoms. More experimental and clinical studies on the effects of physical activity on GI-tract disorders are warranted. Especially, the association between the exercise intensity and data addressing the underlying mechanism(s) of the exercise as the complementary therapy in the treatment of gastrointestinal disorders, require further determination in animal models and humans. PMID- 29788877 TI - Contribution of NRF2 in Gastrointestinal Protection from Oxidative Injury. AB - The human gastrointestinal tract is exposed to a variety of toxic agents, such as Helicobacter pylori (H.pylori), Nonsteroidal Anti-inflammatory Drugs (NSAIDs), gastric acid, enteric pathogenic bacteria, excessive auto immune reactions, and chronic mental stresses. These stressors generate free radicals within the gastrointestinal tissues, causing chronic inflammatory diseases, ulcers, cancers, and functional disturbances. Recent studies have demonstrated that some natural food compounds upregulate the nuclear factor erythroid 2-related factor 2- mediated antioxidant system, ameliorating or preventing these disorders. We have previously shown that dietary intake of sulforaphane-rich broccoli sprouts, ameliorates gastric inflammation induced by H. pylori, prevents NSAIDs-induced small intestinal injury, and improve functional constipation. There have been many other compounds, which enhance the nuclear factor erythroid 2-related factor 2-mediated antioxidant system, sufficient evidence for their clinical efficacy has not yet been provided. In addition, we have to pay attention to some reports, which have shown that excessive stimulation of nuclear factor erythroid 2-related factor 2 enhance chemoresistance and facilitates growth of cancer cells. PMID- 29788878 TI - Cocrystal and its Application in the Field of Active Pharmaceutical Ingredients and Food Ingredients. AB - BACKGROUND: The development of solid drug dosage form and food ingredients is constrained by their low solubility, low dissolution, low bioavailability and poor physicochemical properties. Formation of cocrystal is a novel and promising method to enhance and improve the properties of materials without breaking the covalent bonds. METHODS: The goal of this review is to summarize the cocrystals and their applications in the field of Active Pharmaceutical Ingredients (APIs) and food ingredients (AFIs), mainly on the effective improvements of APIs' and AFIs' pharmacokinetic, physicochemical and mechanical properties by the formation of cocrystals. RESULTS: After years of research and development on cocrystals in the area of pharmaceutical and food industries, significant progress has been made. Formation of cocrystal is an efficient method for improving the solubility, dissolution rate, permeability and in vivo bioavailability of APIs and AFIs, as well as for enhancing stability and mechanical properties. CONCLUSION: Cocrystals exhibit complex structures which can conspicuously affect the physical and chemical properties of original substance, with good clinical performance and outstanding stability during processing and storage. PMID- 29788879 TI - Phase Behavior of Polymorphic Fats in Drug Delivery Systems - A Review of the State of Art. AB - Fats are essential nutrients that have a significant role in the human diet and are essential to provide energy. Fatty acids are present in several types of lipids, such as triglycerides and phospholipids. Fatty acids differ among them, depending on the number of double bonds and on the length of the hydrocarbon chains. If there are no double bonds, the fatty acids are considered saturated and show a linear structure. Compounds with double bonds are unsaturated and have bent structure. The saturated fatty acids are usually solid at room temperature and the unsaturated fatty acids are liquid at that very same temperature. These compounds are of recognized value as raw materials for drug delivery systems, such as lipid nanoparticles. The behaviour of the macroscopic aspects of fat polymorphisms is directly influenced by the melting point, the crystallization and their polymorphic transformations. In this work, we revise the most critical factors contributing for the long-term stability of lipid nanoparticles, as well as the influence of the polymorphism on the loading capacity for drug molecules. PMID- 29788880 TI - Recent Advances in Nanosuspension Technology for Drug Delivery. AB - BACKGROUND: Discovery and development of BCS class 1 drugs through high throughput screening is one of the biggest challenge faced by formulation scientist. METHODS: There are a number of approaches that have been exploited to enhance the solubility and permeability of drugs. Among them, development of nanosuspension has offered several benefits. These techniques may increase effective surface area due to nanonization of drug particles and further increases saturation solubility and dissolution properties for improved bioavailability. Various development methods are patented which are cost effective and easy to scale up. CONCLUSION: Several unique features of nanosuspension make it a versatile delivery system for different routes of administration including oral, dermal, ocular, parenteral and pulmonary. The present review is focused on preparatory techniques and formulation considerations of nanosuspension. Brief information about evaluation parameters, applications of nanosuspension in drug delivery and patented and marketed products available is also discussed. PMID- 29788881 TI - Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology. AB - BACKGROUND: In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. OBJECTIVES: Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. METHODS: Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. RESULTS: The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12+/-0.951% and 86.07+/-1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. CONCLUSION: The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide. PMID- 29788882 TI - Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Taxus-based Drug Development. AB - BACKGROUND: Drug Metabolism and Pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds. Natural and semi-synthetic taxanes may cause and could be affected by Drug-drug Interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. METHOD: Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. RESULTS AND CONCLUSION: DDIs significantly impact the PK/pharmacodynamics performance of taxanes and coadministered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus - involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial to the translation of bench findings to the clinical applications. PMID- 29788885 TI - Application of Traditional Chinese Herbal Medicine By-products as Dietary Feed Supplements and Antibiotic Replacements in Animal Production. AB - Misuse of synthetic antibiotics in livestock leads to the transfer of antibiotic resistant pathogens into humans and deposits toxic residues in meat and milk. There is therefore an urgent need for safe and viable alternative approaches to improve the nutrition and wellbeing of farm animals. An alternative source that has been widely exploited is traditional Chinese herbal medicine (TCHM). These herbal medicines are an important part of the healthcare system in many Asian countries. Such herbs contain several but less toxic bioactive compounds which are generally regarded biodegradable. Recently, advances in knowledge on the importance of TCHM have led to a rapid increase in its production and hence, increasing the amount of by-products generated. Such by-products have become a serious environmental challenge because producers regard them as industrial waste and discard them directly. Incorporating TCHM by-products as feed additives to improve animal health and nutrition has been proposed because they contain high amounts of bioactive compounds which confer several health benefits to animals. TCHM by-products as feed additives apart from being a good alternative for synthetic antibiotics could also minimize the current environmental challenges associated with its disposal. This review summarizes scientific findings on the bioactive compounds in TCHM and TCHM by-products, discusses functional dietary patterns and outlines challenges that may hinder full utilization of TCHM by products in animal production. PMID- 29788886 TI - Novel Pharmacotherapeutic Approaches in Treatment of Alcohol Addiction. AB - In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction has been a global endeavor. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as an adjunct in combination therapy. This review article summarizes the novel pharmacotherapeutic approaches used in the treatment of alcohol addiction by focusing on the drugs, which include neramexane, gabapentin, baclofen, aripiprazole, nalmafene, and quetiapine. PMID- 29788884 TI - Progress of Oral Insulin and Related Drug Delivery Systems and their Pharmacokinetics. AB - BACKGROUND: As society has developed and living standards have improved, diabetes has become a severe public health issue. Insulin plays a crucial role in managing hyperglycemia caused by type I diabetes and particular type II diabetes. Many researchers are seeking alternative, more acceptable methods of insulin delivery, such as oral insulin. An oral formulation has become a new goal for insulin delivery in recent years. METHODS: The PubMed and CNKI databases were searched for "oral insulin, " "drug delivery systems, " and "pharmacokinetics, " and 85 relevant articles were selected from the results as material for this review. These papers were authoritative and had a higher number of citations. RESULTS: Oral insulin would be highly advantageous but is poorly absorbed. The main reason for low absorptivity is the hydrolysis of insulin by enzymes in the gastrointestinal tract. Lack of active transport vectors that pass through the intestinal epithelium is also a non-negligible problem. Additional issues need to be considered to facilitate appropriate research, such as long-term efficacy and safety, clinical data, and toxicological characteristics. CONCLUSION: This review summarized recent advances in oral insulin and the pharmacokinetic profile of the suitable delivery system, providing valuable reference material for future research. PMID- 29788887 TI - Designing Peptidomimetics. AB - The concept of a peptidomimetic was coined about forty years ago. Since then, enormous effort and interest have been devoted to mimic the properties of peptides with small molecules or pseudopeptides. The present report aims to review different approaches described in the past to succeed in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry approach, where parts of the peptide are successively replaced by non-peptide moieties until getting a non-peptide molecule and a biophysical approach, where a hypothesis of the bioactive form of the peptide is sketched and peptidomimetics are designed based on hanging the appropriate chemical moieties on diverse scaffolds. Although both approaches have been used in the past, the former has been more widely used to design peptidomimetics of secretory peptides, whereas the latter is nowadays getting momentum with the recent interest in designing protein-protein interaction inhibitors. The present report summarizes the relevance of the information gathered from structure activity studies, together with a short review of the strategies used to design new peptide analogs and surrogates. In the following section, there is a short discussion on the characterization of the bioactive conformation of a peptide, to continue describing the process of designing conformationally constrained analogs producing first and second generation peptidomimetics. Finally, there is a section devoted to reviewing the use of organic scaffolds to design peptidomimetics based on the information available on the bioactive conformation of the peptide. PMID- 29788883 TI - Models of Drug Induced Liver Injury (DILI) - Current Issues and Future Perspectives. AB - BACKGROUND: Drug-induced Liver Injury (DILI) is an important cause of acute liver failure cases in the United States, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. METHODS: A structured search of bibliographic databases - Web of Science Core Collection, Scopus and Medline for peer-reviewed articles on models of DILI was performed. The reference lists of relevant studies was prepared and a citation search for the included studies was carried out. In addition, the characteristics of screened studies were described. RESULTS: One hundred and six articles about the existing knowledge of appropriate models to study DILI in vitro and in vivo with special focus on hepatic cell models, variations of 3D co-cultures, animal models, databases and predictive modeling and translational biomarkers developed to understand the mechanisms and pathophysiology of DILI are described. CONCLUSION: Besides descriptions of current applications of existing modeling systems, associated advantages and limitations of each modeling system and future directions for research development are discussed as well. PMID- 29788889 TI - Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy. AB - Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction to the computational approaches in GLUT-mediated drug transport and tumor targeting. PMID- 29788890 TI - Inhibition of Pyruvate Dehydrogenase Kinase as a Therapeutic Strategy against Cancer. AB - Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate Dehydrogenase Kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1alpha subunit of pyruvate dehydrogenase complex (PDC) and inactivates it. PDC decarboxylates pyruvate to acetyl CoA, which is further metabolized in mitochondria. Overexpression of PDK was observed in several tumors and is frequently associated with chemotherapy related drug resistance, invasion and metastasis. Elevated expression of PDK leads to a shift in glucose metabolism towards glycolysis instead of oxidative phosphorylation. This review summarizes recent literature related to the role of PDKs in cancer and their inhibition as a strategy. In particular, we discuss the role of PDK in tumor progression, metabolic reprogramming in stem cells, and their regulation by miRNAs and lncRNAs, oncogenes and tumor suppressors. Further, we review strategies aimed at targeting PDK to halt tumor growth and progression. PMID- 29788891 TI - Targeting Sugar Uptake and Metabolism for Cancer Identification and Therapy: An Overview. AB - Metabolic deregulations have emerged as a cancer characteristic, opening a broad avenue for strategies and tools to target cancer through sugar uptake and metabolism. High expression levels of sugar transporters in cancer cells offered glycoconjugation as an approach to achieve enhanced cellular accumulation of drugs and imaging agents, with the sugar moiety anchoring the bioactive cargo to cancer cells. On the other hand, high demand for sugar nutrients in cancers provided a new avenue to target cancer cells with metabolic or sugar uptake inhibitors to induce cancer cells starvation or death. This overview summarizes recent advances in targeting cancer cells through sugar transport for cancer detection and therapy. PMID- 29788888 TI - SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy. AB - Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment. PMID- 29788893 TI - Triple-Valve Endocarditis in a Diabetic Patient: Case Report and Literature Review. AB - BACKGROUND: Despite major advancements since its first description in the 19th century, infective endocarditis remains a significant medical challenge. Although commonly involving a single valve, multiple valve involvement may occur, complicating matters even further. Triplevalve endocarditis is a very rare phenomenon. Poorly studied and described only a handful of times in the literature, little is known about the optimal therapeutic and management options in dealing with this complex entity. CONCLUSION: In this paper we describe the case of a 48-year-old male who was diagnosed with triple-valve endocarditis and provide a review of the literature to delineate what is already known and improve our understanding of this rare phenomenon. PMID- 29788894 TI - Rotational Atherectomy in Acute STEMI with Heavily Calcified Culprit Lesion is a Rule Breaking Solution. AB - BACKGROUND: Calcified coronary lesions represent technical challenges during percutaneous coronary intervention and are associated with a high frequency of restenosis and target lesion revascularization. Rotational atherectomy has been shown to increase procedural success in severely calcified lesions, facilitate stent delivery in undilatable lesions and ensure complete stent expansion. However, rotational atherectomy in ST-elevation Myocardial Infarction (STEMI) is traditionally avoided given the concern for slow or no reflow and considered a contraindication in lesions with a visible thrombus by its manufacturer (Rotablator, Boston Scientific). CONCLUSION: This case demonstrates the successful use of rotational atherectomy to facilitate dilation and revascularization of a heavily calcified culprit lesions in a patient with acute anterior STEMI with ongoing chest pain. PMID- 29788896 TI - Association Between Delayed Graft Function (DGF) Biomarkers and Long-term Outcomes After Living Donor Kidney Transplantation. AB - BACKGROUND AND OBJECTIVES: The association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interleukin-18 (uIL-18) with poor 1 year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is an association between these postoperative biomarkers with important recipient outcomes beyond this time in livedonor transplants. METHODS: NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Moreover, the association between delayed graft function with clinical outcome and Serum Creatinine (SrCr) was evaluated during this period. RESULTS: The Mean age for kidney recipients was 23.9 years. Significant interaction was observed between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). CONCLUSION: Changes in urine NGAL postoperative are associated with worst outcomes, 2 years after kidney transplantation, suggesting its potential role in identifying patients that are at high risk for diminished allograft function, outcome and survival. PMID- 29788892 TI - Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer. AB - Cancer cells have a very different metabolism from that of normal cells from which they are derived. Their metabolism is elevated, which allows them to sustain higher proliferative rate and resist some cell death signals. This phenomenon, known as the "Warburg effect", has become the focus of intensive efforts in the discovery of new therapeutic targets and new cancer drugs. Both glycolysis and glutaminolysis pathways are enhanced in cancer cells. While glycolysis is enhanced to satisfy the increasing energy demand of cancer cells, glutaminolysis is enhanced to provide biosynthetic precursors for cancer cells. It was recently discovered that there is a tyrosine phosphorylation of a specific isoform of pyruvate kinase, the M2 isoform, that is preferentially expressed in all cancer cells, which results in the generation of pyruvate through a unique enzymatic mechanism that is uncoupled from ATP production. Pyruvate produced through this unique enzymatic mechanism is converted primarily into lactic acid, rather than acetyl-CoA for the synthesis of citrate, which would normally then enter the citric acid cycle. Inhibition of key enzymes in glycolysis and glutaminolysis pathways with small molecules has provided a novel but emerging area of cancer research and has been proven effective in slowing the proliferation of cancer cells, with several inhibitors being in clinical trials. This review paper will cover recent advances in the development of chemotherapeutic agents against several metabolic targets for cancer therapy, including glucose transporters, hexokinase, pyruvate kinase M2, glutaminase, and isocitrate dehydrogenase. PMID- 29788897 TI - Biofilm Destruction on Endotracheal Tubes by Photodynamic Inactivation. AB - BACKGROUND: Hospital infections are a public health problem that can occur with the use of catheters and endotracheal tubes (ETT). Pathogenic microorganisms may adhere to surfaces of these materials forming a biofilm and produce an extracellular polymer matrix that promotes resistance of microorganisms to factors such as pH, temperature and drugs. The conventional treatment is being made by antibiotics, which has serious adverse effects in immunocompromised patients. Photodynamic therapy (PDT) is an alternative for microbial inactivation noninvasive without the stimulus of microbial resistance. PDT combines light and a photosensitive molecule for produce reactive oxygen species leading to bacterial death. OBJECTIVE: The objective of this study was to determine the efficacy of a PDT protocol in bacterial inactivation of biofilm ETT. METHOD: The photosensitizer (PS) used was curcumin and the light source LED at 450nm. A statistical experimental design was used for optimization of antimicrobial PDT. RESULTS: The highest microbial inactivation was observed with 70% biofilm reduction in conditions 1.25 mg/mL curcumin, 2 h of PS incubation and 50 J/cm2. CONCLUSION: This study described the photodynamic death of bacteria forming a biofilm on ETT. Parameters optimization was important for clinical application of this system. PMID- 29788895 TI - Synthesis of Nucleosides and Non-nucleosides Based 4,6-disubstituted-2-oxo dihydropyridine-3-carbonitriles as Antiviral Agents. AB - BACKGROUND: Viral diseases are considered main threats that face the humanity worldwide. The emergence of new viruses like influenza viruses emphasizes the significance of designing novel antiviral drugs. METHOD: The aim of this work is to synthesize a new set of nucleoside and non-nucleoside cyanopyridine, characterized and evaluated for their in vitro antiviral properties against various strains. CONCLUSION: More of the compounds showed variable antiviral potential against a panel of eighteen DNA and RNA viruses. The screening data suggested that the order of activity of the active compounds are in the order of O-glycosyl > O-alkyl > N-alkyl > S-alkyl derivatives. In addition, the 4-fluoro substituted compounds are more effective among the O- and N-alkyl analogs, whereas remarkable antiviral activity was ascribed to the methoxylated O-glycosyl derivatives. Most of the active compounds proved to be more selective towards the inhibition of the replication of DNA rather than the RNA-viruses. The analogs 1a, 2a, 12b, 14b and 16b possessed broad spectrum and noticeable antiviral potential against most of the tested DNA- and RNA-viruses (EC50 ~ 0.8-20 uM), accompanied with considerably low cytotoxic margin (MCC ~ 4-20 uM), and comparable with reference standard antiviral agents. PMID- 29788898 TI - Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs. PMID- 29788899 TI - Topical Nanostructured Lipid Carrier Based Hydrogel of Mometasone Furoate for the Treatment of Psoriasis. AB - OBJECTIVE: The aim of the present study was to develop and evaluate nanostructured lipid carrier based topical hydrogel of mometasone furoate for the treatment of psoriasis. METHOD: Drug loaded NLCs were successfully developed by microemulsion technique. Pseudo ternary phase diagrams were constructed using different combinations of surfactant and co-surfactants to study the microemulsion existence range. Different compositions were selected from the phase diagram showing maximum microemulsion region and were converted into NLCs by dilution in water (1:20). The optimized formulation was characterised for droplet size, zeta potential, entrapment efficiency and morphology was studied using Transmission Electron Microscopy. Ex vivo permeation studies were carried out using Wistar rat skin. The potential of this formulation in treating psoriatic inflammation was studied using imiquimod induced skin inflammation animal model. RESULTS: The optimized formulation (F4) has droplet size of 163.2+/ 0.522 nm, zeta potential - 0.086+/-0.099 mV and entrapment efficiency of 60.0+/ 0.187%. Transmission electron microscopy confirmed spherical shape of nanostructured lipid carrier. Carbopol 940 was used to convert NLC dispersion into NLC based hydrogel to improve its viscosity for topical administration. Drug permeation studies showed prolonged drug release from the NLC based gel as compared to marketed formulation following Higuchi release kinetics. The skin deposition of MF loaded NLC based hydrogel was found to 2.5 fold higher than marketed formulation with primary skin irritation index of 0.20. In vivo studies showed complete clearance of parakeratosis by treatment with the prepared NLC formulation. Accelerated stability studies signify high robustness scale of optimized formulation under one month storage period. CONCLUSION: The prepared NLC based formulation has proved to be a promising carrier system for the treatment of psoriasis. PMID- 29788900 TI - Association between vascular comorbidity and progression of Alzheimer's disease: a two-year observational study in Norwegian memory clinics. AB - BACKGROUND: Vascular risk factors increase the risk of Alzheimer's disease (AD), but there is limited evidence on whether comorbid vascular conditions and risk factors have an impact on disease progression. The aim of this study was to examine the association between vascular disease and vascular risk factors and progression of AD. METHODS: In a longitudinal observational study in three Norwegian memory clinics, 282 AD patients (mean age 73.3 years, 54% female) were followed for mean 24 (16-37) months. Vascular risk factors and vascular diseases were registered at baseline, and the vascular burden was estimated by the Framingham Stroke Risk Profile (FSRP). Cerebral medical resonance images (MRIs) were assessed for white matter hyperintensities (WMH), lacunar and cortical infarcts. The associations between vascular comorbidity and progression of dementia as measured by annual change in Clinical Dementia Rating Sum of Boxes (CDR-SB) scores were analysed by multiple regression analyses, adjusted for age and sex. RESULTS: Hypertension occurred in 83%, hypercholesterolemia in 53%, diabetes in 9%, 41% were overweight, and 10% were smokers. One third had a history of vascular disease; 16% had heart disease and 15% had experienced a cerebrovascular event. MRI showed lacunar infarcts in 16%, WMH with Fazekas score 2 in 26%, and Fazekas score 3 in 33%. Neither the vascular risk factors and diseases, the FSRP score, nor cerebrovascular disease was associated with disease progression in AD. CONCLUSIONS: Although vascular risk factors and vascular diseases were prevalent, no impact on the progression of AD after 2 years was shown. PMID- 29788901 TI - Recurrent esophageal stricture from previous caustic ingestion treated with 40 year self-dilation: case report and review of literature. AB - BACKGROUND: Corrosive esophageal strictures are common. The severity of the strictures depends on type, quantity, duration of contact and concentration of the caustic substance ingested. Endoscopic balloon dilation and endoscopic bougienage are a cornerstone in the management of the benign esophageal strictures and are the most widely used treatments, but are expensive and invasive procedures. CASE PRESENTATION: We report the case of an 82-year-old patient with a corrosive esophageal stricture treated for over 40 years by means of home self-bougienage. The procedure has been carried out for the longest lapse of time described in literature, with an excellent control of symptoms. In the case reported, after being carried out for more than 40 years, self-dilation allowed good quality of life and symptoms management, ensuring an excellent nutritional status. CONCLUSIONS: Following an adequate patient training, self dilatation can be a safe and effective option of treatment, avoiding frequent expensive hospital admissions for endoscopic esophageal dilatation. PMID- 29788902 TI - Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation. AB - BACKGROUND: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally. CASE PRESENTATION: A 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum bilaterally. The Burke-Fahn-Marsden Dystonia Rating Scale motor/disability scores improved from 87/25 to 21/13 at 2.5 months postoperatively, 26/14 at 3 years, and 30/14 at 4 years. Subsequent whole exome sequencing identified heterozygosity for the ACTB p.Arg183Trp variant. Brain imaging included 123I-ioflupane single photon emission computed tomography (Dopamine Transporter-SPECT), SPECT with 123I-epidepride (binds to dopamine type 2-receptors) and 18 Fluoro-Deoxy-Glucose (FDG)-PET. Both Epidepride-SPECT and FDG PET showed reduced tracer uptake in the striatum bilaterally, particularly in the putamen. DaT-SPECT was slightly abnormal. CONCLUSIONS: In this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures. PMID- 29788903 TI - Sustained efficacy following resolution of frequent heartburn with an over-the counter regimen of esomeprazole 20 mg or placebo for 14 days: two randomized trials. AB - BACKGROUND: A two-week course of therapy with an over-the-counter proton-pump inhibitor (PPI) is recommended for frequent heartburn. Limited research has been conducted on the sustained efficacy of short-term PPI therapy after treatment cessation. Esomeprazole 20 mg was evaluated in the seven-day follow-up period after the two-week treatment period using pooled data from two identical randomized, double-blind, placebo-controlled studies. METHODS: Adults without confirmed diagnoses of gastroesophageal reflux disease experiencing heartburn at least two days/week in the past four weeks were eligible. Subjects received treatment with esomeprazole 20 mg or placebo once daily for 14 days. Heartburn episodes were documented using daily diaries. Missing data during the two-week treatment period were assumed to be days with heartburn. The proportion of subjects with heartburn resolution while on treatment and during the seven days of follow-up was assessed. Predictors of resolution during this post-treatment period were evaluated using a stepwise logistic regression model. RESULTS: All subjects in the pooled analysis set who reported diary data for at least three follow-up days were analyzed (N = 584). This cut-off was used to ensure that sufficient data were collected for these analyses. Greater run-in heartburn frequency was a significant negative predictor of heartburn resolution during follow-up (P < 0.001). Among the on-treatment efficacy variables, the best predictor of resolution during follow-up was resolution during the last seven days of treatment (odds ratio: 3.81 [95% confidence interval: 2.40, 6.05; P < 0.0001]). CONCLUSIONS: Lower baseline heartburn frequency and heartburn resolution during the last seven days of treatment were associated with a greater likelihood of heartburn resolution during the seven-day follow-up. TRIAL REGISTRATION: Registered at ClinicalTrials.gov June 11, 2011: NCT01370525 ; NCT01370538 . PMID- 29788904 TI - Genetic diversity of BoLA-DRB3 in South American Zebu cattle populations. AB - BACKGROUND: Bovine leukocyte antigens (BoLAs) are used extensively as markers of disease and immunological traits in cattle. However, until now, characterization of BoLA gene polymorphisms in Zebu breeds using high resolution typing methods has been poor. Here, we used a polymerase chain reaction sequence-based typing (PCR-SBT) method to sequence exon 2 of the BoLA class II DRB3 gene from 421 cattle (116 Bolivian Nellore, 110 Bolivian Gir, and 195 Peruvian Nellore Brahman). Data from 1416 Taurine and Zebu samples were also included in the analysis. RESULTS: We identified 46 previously reported alleles and no novel variants. Of note, 1/3 of the alleles were detected only in Zebu cattle. Comparison of the degree of genetic variability at the population and sequence levels with genetic distance in the three above mentioned breeds and nine previously reported breeds revealed that Zebu breeds had a gene diversity score higher than 0.86, a nucleotide diversity score higher than 0.06, and a mean number of pairwise differences greater than 16, being similar to those estimated for other cattle breeds. A neutrality test revealed that only Nellore-Brahman cattle showed the even gene frequency distribution expected under a balanced selection scenario. The FST index and the exact G test showed significant differences across all cattle populations (FST = 0.057; p < 0.001). Neighbor joining trees and principal component analysis identified two major clusters: one comprising mainly European Taurine breeds and a second comprising Zebu breeds. This is consistent with the historical and geographical origin of these breeds. Some of these differences may be explained by variation of amino acid motifs at antigen-binding sites. CONCLUSIONS: The results presented herein show that the historical divergence between Taurine and Zebu cattle breeds is a result of origin, selection, and adaptation events, which would explain the observed differences in BoLA-DRB3 gene diversity between the two major bovine types. This allelic information will be important for investigating the relationship between the major histocompatibility complex and disease, and contribute to an ongoing effort to catalog bovine MHC allele frequencies according to breed and location. PMID- 29788905 TI - Genomic prediction of the polled and horned phenotypes in Merino sheep. AB - BACKGROUND: In horned sheep breeds, breeding for polledness has been of interest for decades. The objective of this study was to improve prediction of the horned and polled phenotypes using horn scores classified as polled, scurs, knobs or horns. Derived phenotypes polled/non-polled (P/NP) and horned/non-horned (H/NH) were used to test four different strategies for prediction in 4001 purebred Merino sheep. These strategies include the use of single 'single nucleotide polymorphism' (SNP) genotypes, multiple-SNP haplotypes, genome-wide and chromosome-wide genomic best linear unbiased prediction and information from imputed sequence variants from the region including the RXFP2 gene. Low-density genotypes of these animals were imputed to the Illumina Ovine high-density (600k) chip and the 1.78-kb insertion polymorphism in RXFP2 was included in the imputation process to whole-genome sequence. We evaluated the mode of inheritance and validated models by a fivefold cross-validation and across- and between family prediction. RESULTS: The most significant SNPs for prediction of P/NP and H/NH were OAR10_29546872.1 and OAR10_29458450, respectively, located on chromosome 10 close to the 1.78-kb insertion at 29.5 Mb. The mode of inheritance included an additive effect and a sex-dependent effect for dominance for P/NP and a sex-dependent additive and dominance effect for H/NH. Models with the highest prediction accuracies for H/NH used either single SNPs or 3-SNP haplotypes and included a polygenic effect estimated based on traditional pedigree relationships. Prediction accuracies for H/NH were 0.323 for females and 0.725 for males. For predicting P/NP, the best models were the same as for H/NH but included a genomic relationship matrix with accuracies of 0.713 for females and 0.620 for males. CONCLUSIONS: Our results show that prediction accuracy is high using a single SNP, but does not reach 1 since the causative mutation is not genotyped. Incomplete penetrance or allelic heterogeneity, which can influence expression of the phenotype, may explain why prediction accuracy did not approach 1 with any of the genetic models tested here. Nevertheless, a breeding program to eradicate horns from Merino sheep can be effective by selecting genotypes GG of SNP OAR10_29458450 or TT of SNP OAR10_29546872.1 since all sheep with these genotypes will be non-horned. PMID- 29788906 TI - Influences on the adoption of patient safety innovation in primary care: a qualitative exploration of staff perspectives. AB - BACKGROUND: Primary care is changing rapidly to meet the needs of an ageing and chronically ill population. New ways of working are called for yet the introduction of innovative service interventions is complicated by organisational challenges arising from its scale and diversity and the growing complexity of patients and their care. One such intervention is the multi-strand, single platform, Patient Safety Toolkit developed to help practices provide safer care in this dynamic and pressured environment where the likelihood of adverse incidents is increasing. Here we describe the attitudes of staff toward these tools and how their implementation was shaped by a number of contextual factors specific to each practice. METHODS: The Patient Safety Toolkit comprised six tools; a system of rapid note review, an online staff survey, a patient safety questionnaire, prescribing safety indicators, a medicines reconciliation tool, and a safe systems checklist. We implemented these tools at practices across the Midlands, the North West, and the South Coast of England and conducted semi structured interviews to determine staff perspectives on their effectiveness and applicability. RESULTS: The Toolkit was used in 46 practices and a total of 39 follow-up interviews were conducted. Three key influences emerged on the implementation of the Toolkit these related to their ease of use and the novelty of the information they provide; whether their implementation required additional staff training or practice resource; and finally factors specific to the practice's local environment such as overlapping initiatives orchestrated by their CCG. CONCLUSIONS: The concept of a balanced toolkit to address a range of safety issues proved popular. A number of barriers and facilitators emerged in particular those tools that provided relevant information with a minimum impact on practice resource were favoured. Individual practice circumstances also played a role. Practices with IT aware staff were at an advantage and those previously utilising patient safety initiatives were less likely to adopt additional tools with overlapping outputs. By acknowledging these influences we can better interpret reaction to and adoption of individual elements of the toolkit and optimise future implementation. PMID- 29788907 TI - Mycobacterium Avium complex vertebral osteomyelitis in the absence of HIV infection: a case report and review. AB - BACKGROUND: Mycobacterium Avium Complex (MAC) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. However, MAC manifesting as vertebral osteomyelitis is less common, and is particularly rare in the absence of Acquired Immunodeficiency Syndrome (AIDS). Prompt diagnosis of MAC vertebral osteomyelitis is challenging, but necessary to prevent serious morbidity or mortality. CASE PRESENTATION: We report a case of MAC osteomyelitis of the lumbar spine in a 70 year-old woman on extended duration corticosteroid therapy for systemic lupus erythematosus who presented with progressive back pain. Upon presentation, imaging revealed osteomyelitis of the lumbar spine with associated paraspinal abscess. Cultures from the surgical evacuation of the paraspinal abscess yielded no pathogen growth and she was therefore treated with empiric antibacterial therapy. Two weeks after her initial hospital discharge she represented with severe back pain and radiologic evidence of progressive disease in her lumbar spine. Two additional vertebral biopsies were required during her first 2 weeks of admission. MAC eventually grew from culture 14 days after collection. She was treated with ethambutol and rifampin and her symptoms resolved in 2 weeks, though therapy was continued for 12 months. CONCLUSIONS: MAC is an unusual cause of vertebral osteomyelitis in patients with AIDS, but is exceedingly rare in those without severe immune compromise. Despite its rarity, it must be considered in cases of vertebral osteomyelitis that do not respond to empiric antibiotic therapy. Multiple biopsies may be necessary to obtain a diagnosis and avoid destructive infectious complications of an untreated infection. PMID- 29788908 TI - Perceptions of insulin use in type 2 diabetes in primary care: a thematic synthesis. AB - BACKGROUND: Increasing numbers of patients with type 2 diabetes mellitus are progressing to insulin therapy, and despite its potency many such individuals still have suboptimal glycaemic control. Insulin initiation and intensification is now often conducted by Practice Nurses and General Practitioners in many parts of the UK. Therefore, gaining insight into perspectives of patients and primary care clinicians is important in determining self-management and engagement with insulin. A thematic synthesis of studies was conducted exploring the views and experiences of people with type 2 diabetes and of healthcare professionals on insulin use and management in the context of primary care. METHODS: Protocol based systematic searches of electronic databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Web of Science) were performed on 1 October 2014 and updated on 31 March 2015, to identify studies that identified the views and experiences of adults with type 2 diabetes or primary care clinicians on the use of insulin in the management of type 2 diabetes. Studies meeting the review inclusion criteria were critically appraised using the CASP qualitative research checklist or Barley's checklist for survey designs. A thematic synthesis was then conducted of the collected studies. RESULTS: Thirty-four studies were selected. Of these, 12 used qualitative interviews (nine with patients and three with healthcare professionals) and 22 were survey based (14 with patients, three with healthcare professionals, and five with both). Twelve key themes were identified and formed three domains, patient perceptions, healthcare professional perceptions, and health professional-patient relationships. The patient-centred themes were: insulin-related beliefs, social influences, psychological factors, hypoglycaemia, and therapy barriers. The clinician-related themes were: insulin skills of general practitioners, healthcare integration, healthcare professional perceived barriers, hypoglycaemia, and explanations for adherence. Healthcare professional-patient relationship themes were drawn from the perspectives of patients and from clinicians. CONCLUSIONS: This review reveals multiple barriers to optimal insulin use in primary care at both the patient and healthcare professional levels. These barriers indicate the need for multimodal interventions to: improve the knowledge and competencies of primary care professionals in insulin use; provide more effective patient education and self management support; and introduce integrated insulin support systems. PMID- 29788910 TI - Infection with high proportion of multidrug-resistant bacteria in conflict related injuries is associated with poor outcomes and excess resource consumption: a cohort study of Syrian patients treated in Jordan. AB - BACKGROUND: Armed conflicts are a major contributor to injury and death globally. Conflict-related injuries are associated with a high risk of wound infection, but it is unknown to what extent infection directly relates to sustainment of life and restoration of function. The aim of this study was to investigate the outcome and resource consumption among civilians receiving acute surgical treatment due to conflict-related injuries. Patients with and without wound infections were compared. METHODS: We performed a cohort study using routinely collected data from 457 consecutive Syrian civilians that received surgical treatment for acute conflict-related injuries during 2014-2016 at a Jordanian hospital supported by Medecins Sans Frontieres. We defined wound infection as clinical signs of infection verified by a positive culture. We used logistic regression models to evaluate infection-related differences in outcome and resource consumption. RESULTS: Wound infection was verified in 49/457 (11%) patients. Multidrug resistance (MDR) was detected in 36/49 (73%) of patients with infection. Among patients with infection, 11/49 (22%) were amputated, compared to 37/408 (9%) without infection, crude relative risk = 2.62 (95% confidence interval 1.42 4.81). Infected patients needed 12 surgeries on average, compared to five in non infected patients (p < .00001). Mean length of stay was 77 days for patients with infection, and 35 days for patients without infection (p = .000001). CONCLUSIONS: Among Syrian civilians, infected conflict-related wounds had a high prevalence of MDR bacteria. Wound infection was associated with poor outcomes and high resource consumption. These results could guide the development of antibiotic protocols and adaptations of surgical management to improve care for wound infections in conflict-related injuries. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02744144 ). Registered April 13, 2016. Retrospectively registered. PMID- 29788909 TI - Whole genome analysis reveals the diversity and evolutionary relationships between necrotic enteritis-causing strains of Clostridium perfringens. AB - BACKGROUND: Clostridium perfringens causes a range of diseases in animals and humans including necrotic enteritis in chickens and food poisoning and gas gangrene in humans. Necrotic enteritis is of concern in commercial chicken production due to the cost of the implementation of infection control measures and to productivity losses. This study has focused on the genomic analysis of a range of chicken-derived C. perfringens isolates, from around the world and from different years. The genomes were sequenced and compared with 20 genomes available from public databases, which were from a diverse collection of isolates from chickens, other animals, and humans. We used a distance based phylogeny that was constructed based on gene content rather than sequence identity. Similarity between strains was defined as the number of genes that they have in common divided by their total number of genes. In this type of phylogenetic analysis, evolutionary distance can be interpreted in terms of evolutionary events such as acquisition and loss of genes, whereas the underlying properties (the gene content) can be interpreted in terms of function. We also compared these methods to the sequence-based phylogeny of the core genome. RESULTS: Distinct pathogenic clades of necrotic enteritis-causing C. perfringens were identified. They were characterised by variable regions encoded on the chromosome, with predicted roles in capsule production, adhesion, inhibition of related strains, phage integration, and metabolism. Some strains have almost identical genomes, even though they were isolated from different geographic regions at various times, while other highly distant genomes appear to result in similar outcomes with regard to virulence and pathogenesis. CONCLUSIONS: The high level of diversity in chicken isolates suggests there is no reliable factor that defines a chicken strain of C. perfringens, however, disease-causing strains can be defined by the presence of netB-encoding plasmids. This study reveals that horizontal gene transfer appears to play a significant role in genetic variation of the C. perfringens chromosome as well as the plasmid content within strains. PMID- 29788911 TI - What drives the shift between sexual and clonal reproduction of Caragana stenophylla along a climatic aridity gradient? AB - BACKGROUND: The reasons that clonal plants shift between sexual and clonal reproduction have persisted as a knowledge gap in ecological literature. We hypothesized that clonal plants' shifts between sexual and clonal reproduction in different environments are driven by the relative costs of sexual and clonal reproduction. Moreover, we hypothesized plants prioritize sexual reproduction over clonal reproduction. To test these hypotheses, we determined the costs of sexual and clonal reproduction, and proportions of sexual and clonal reproduction of Caragana stenophylla along a climatic aridity gradient (semi-arid, arid, very arid and intensively arid zones) in the Inner Mongolia Steppe using several complementary field experiments. RESULTS: The cost of sexual reproduction increased while the cost of clonal reproduction decreased as climatic drought stress increased from the semi-arid to the intensively arid zones. The changes in the costs of these reproductive modes drove a shift in the reproductive mode of C. stenophylla from more sexual reproduction in the semi-arid zone to more clonal propagation in the intensively arid zone. However, because of the evolutionary advantages of sexual reproduction, sexual reproduction still held priority over clonal production in C. stenophylla, with the priority of sexual reproduction gradually increasing from the semi-arid to the intensively arid zones. CONCLUSIONS: Our study suggested that sexual reproduction has relatively high priority in propagation of C. stenophylla. However, if the costs of sexual reproduction are too high, C. stenophylla likely chooses clonal reproduction, and the ratio between sexual and clonal reproduction could be mediated by reproductive cost. These reproductive strategies reflect optimal resource utilization, and allow the persistence of both reproductive modes across stressful conditions depending on their evolutionary advantages. PMID- 29788913 TI - Prevalence and outcome of injury in patients visiting the emergency Department of Yirgalem General Hospital, Southern Ethiopia. AB - BACKGROUND: Traumatic injuries continue to be an important cause of morbidity and mortality in the developing world. Despite the high burden of injury in Ethiopia, the occurrence and health impact have not received due attention. The aim of the study was to assess the prevalence and outcome of injury among patients visiting the Emergency Department (ED) of Yirgalem General Hospital, southern Ethiopia. METHODS: A facility-based prospective cross sectional study was conducted from March, 27 - April, 30/2017. The final calculated sample size was 353 and all eligible trauma patients who visited the ED of Yirgalem General Hospital during the study period were included in the study. Data was collected using a checklist which was adapted from the WHO injury surveillance guideline. The data were entered and analyzed using SPSS version 19. RESULTS: A total of 346 patients, who visited the ED during the study period, participated in the study and of them, 171 (49.4%) were injury cases. Unintentional injuries accounted 123 (71.9%) of the total injuries and the age group <=24 years (48.2%) was the most commonly affected age group. More than half (51.4%) of unintentional injury cases were due to Road Traffic Injuries (RTIs) and 48 (28%) of the cases were attributed to interpersonal violence (assault). The majority of patients, 97 (56.7%), had a minor or superficial injury (like bruises and minor cuts), 44 (25.7%) had a moderate injury and 16 (9.3%) had severe type of injury requiring intensive medical/surgical management; and RTIs accounted for 11 (68%) of all severe injuries. CONCLUSION: The prevalence of injury was considerably high in Yirgalem General Hospital. Road Traffic Injuries (RTIs) accounted for the majority of severe injury cases; therefore, appropriate prevention strategies should be strengthened and implemented against RTIs. We also suggest that children and young adults should be educated in schools and work environments to prevent injuries/accidents. PMID- 29788912 TI - Association between troponin-I levels and outcome in critically ill patients admitted to non-cardiac intensive care unit with high prevalence of cardiovascular risk factors. AB - BACKGROUND: The association of troponin-I levels and outcome in medical-surgical ICU patients has been studied before in populations with low to moderate prevalence of cardiovascular risk factors. The objective in this article is to examine the association of troponin-I levels with hospital mortality in patients with high prevalence of cardiovascular risk factors who were admitted with medical-surgical indications to a non-cardiac intensive care unit. METHODS: This was a retrospective study of adult patients admitted to a tertiary medical surgical ICU between July 2001 and November 2011. Data were extracted from prospectively collected ICU and clinical laboratory databases. Patients were stratified based on the highest troponin-I level in the first 72 h of admission into four groups (Group I < 0.03, Group II = 0.03-0.3, Group III = 0.3-3 and Group IV > 3 ng/mL). Hospital mortality was the primary outcome. To study the association between elevated troponin-I and hospital mortality, we carried out multivariate logistic regression analyses with Group I as a reference group. RESULTS: During the study period, 3368 patients had troponin-I levels measured in the first 72 h, of whom 1293 (38.3%) were diabetic and 1356 (40.2%) were chronically hypertensive. Among the study population, 2719 (81%) had elevated troponin-I levels (0.03 ng/mL and higher). Hospital mortality increased steadily as the troponin-I levels increased. Hospital mortality was 23.4% for Group I, 33.2% for Group II (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 0.84, 1.38), 49.6% for Group III (aOR = 1.64, 95% CI 1.24, 2.17), and 57.4% for Group IV (aOR 1.80, 95% CI 1.30, 2.49). The association of increased mortality with increased troponin level was observed whether patients had underlying advanced heart failure or not. Subgroup analysis showed an increased mortality in patients aged < 50 years, non-diabetics and not on vasopressors. CONCLUSION: In a population with high prevalence of diabetes and hypertension, elevated troponin-I was frequently observed in medical-surgical critically ill patients, and showed a level-dependent association with hospital mortality. PMID- 29788915 TI - The appropriateness of Bland-Altman's approximate confidence intervals for limits of agreement. AB - BACKGROUND: Percentiles are widely used as reference limits for determining the relative magnitude and substantial importance of quantitative measurements. An important application is the advocated Bland-Altman limits of agreement. METHODS: To contribute to the data analysis and design planning of reference limit or percentile research, the purpose of this paper is twofold. The first is to clarify the statistical features of interval estimation procedures for normal percentiles. The second goal is to provide sample size procedures for precise interval estimation of normal percentiles. RESULTS: The delineation demonstrates the theoretical connections between different pivotal quantities for obtaining exact confidence intervals. Moreover, the seemingly accurate approximate methods with equidistant from the principal estimators are shown to have undesirable confidence limits. It is found that the optimal sample size has a minimum for median or mean, and increases as the percentile approaches the extremes. CONCLUSIONS: The exact interval procedure should be used in preference to the approximate methods. Computer algorithms are presented to implement the suggested interval precision and sample size calculations for planning percentile research. PMID- 29788917 TI - Parental-reported allergic disorders and emergency department presentations for allergy in the first five years of life; a longitudinal birth cohort. AB - BACKGROUND: To measure rates of parental-report of allergic disorders and ED presentations for allergic disorders in children, and to describe factors associated with either. METHODS: An existing cohort of 3404 children born between 2006 and 2011 (Environments for Healthy Living) with prospectively collected pre natal, perinatal and follow-up data were linked to i) nationwide Medicare and pharmaceutical data and ii) Emergency Department (ED) data from four hospitals in Australia. Parental-reported allergy was assessed in those who returned follow-up questionnaires. ED presentation was defined as any presentation for a suite of allergic disorders, excluding asthma. Univariate analysis and multivariate logistic regression were used to descibe risk factors for both parental-reported allergy and ED presentation for an allergic disorder. RESULTS: The incidence of parental-reported child allergy at 1, 3 and 5 years of age was 7.8, 7.8 and 12.6%, respectively. Independent predictors of parental-report of allergy in multivariate analysis were parental-report of asthma (OR 2.2, 95% CI 1.4-3.4) or eczema (OR 4.3, 95% CI 3.1-6.1) and age > 6 months at introduction of solids (OR 1.3, 95% CI 1.0-1.7). Factors associated with ED presentations for allergy, which occurred in 3.6% of the cohort, were presence of maternal asthma (OR 2.3 95% CI:1.1, 4.9) and child born in spring (OR 1.7, 95% CI 1.1, 2.7). CONCLUSIONS: More than 10% of children up to 5 years have a parental-reported allergic disorder, and 3.6% presented to ED. Parental-report of eczema and/or asthma and late introduction of solids were predictors of parental-report of allergy. Spring birth and maternal asthma were predictors for ED presentation for allergy. PMID- 29788914 TI - Nutrition care practices of primary care providers for weight management in multidisciplinary primary care settings in Ontario, Canada - a qualitative study. AB - BACKGROUND: Despite the recommended guidelines on addressing diet for the management and prevention of obesity in primary care, the literature highlights that their implementation has been suboptimal. In this paper, we provide an in depth understanding of current nutrition-related weight management practices of primary care providers (PCPs) working in relatively new multidisciplinary health care settings in Ontario. METHODS: Three types of multidisciplinary primary care settings were included (2 Family Health Teams, 3 Community Health Centres and 1 Nurse Practitioner-Led Clinic). Participants (n = 20) included in this study were nurse practitioners (n = 13) and family physicians (n = 7) supporting care for adult patients (18 years or older). In-depth interviews were transcribed, coded and the content was analyzed using an integrated approach. RESULTS: Our analysis showed that most PCPs used anthropometric measures such as weight for screening patients who would benefit from nutrition counselling with a dietitian. The topic of nutrition was generally brought up either during physical examinations, when patients were diagnosed with a chronic disease, or when blood markers were out of normal range. Participants also mentioned that physical examinations are no longer occurring annually, with most PCPs offering episodic care. All participants reported utilizing dietetic referrals, noting the enablers for providing the referral, which included access to an on-site dietitian. Nonetheless, dietetic referrals were mostly used when patients had an obesity related co-morbidity. Participants mentioned that healthy eating advice was reinforced during follow-up visits with patients only when there was enough time to do so. Electronic Health Records (EHRs) were utilized to facilitate message reinforcement by PCPs, who perceived EHRs to be helpful for viewing what was discussed in the session with the dietitian. CONCLUSIONS: PCPs mostly used objective measures to screen for patients who would benefit from nutrition counselling rather than diet assessment, which undermines the importance of dietary intake and overemphasizes weight. With physical examinations occurring less frequently, there will be additional missed opportunities for addressing nutrition-related concerns. The presence of a dietitian on site allowed for PCPs to refer patients to nutrition counselling. Having sufficient time during medical visits and EHRs seemed to facilitate message reinforcement by PCPs in follow-up visits with patients. PMID- 29788919 TI - Prediction of fluid responsiveness in mechanically ventilated cardiac surgical patients: the performance of seven different functional hemodynamic parameters. AB - BACKGROUND: Functional hemodynamic parameters such as stroke volume and pulse pressure variation (SVV and PPV) have been shown to be reliable predictors of fluid responsiveness in mechanically ventilated patients. Today, different minimally- and non-invasive hemodynamic monitoring systems measure functional hemodynamic parameters. Although some of these parameters are described by the same name, they differ in their measurement technique and thus may provide different results. We aimed to test the performance of seven functional hemodynamic parameters simultaneously in the same clinical setting. METHODS: Hemodynamic measurements were done in 30 cardiac surgery patients that were mechanically ventilated. Before and after a standardized intravenous fluid bolus, hemodynamics were measured by the following monitoring systems: PiCCOplus (SVVPiCCO, PPVPiCCO), LiDCOrapid (SVVLiDCO, PPVLiDCO), FloTrac (SVVFloTrac), Philips Intellivue (PPVPhilips) and Masimo pulse oximeter (pleth variability index, PVI). Prediction of fluid responsiveness was tested by calculation of receiver operating characteristic (ROC) curves including a gray zone approach and compared using Fisher's Z-Test. RESULTS: Fluid administration resulted in an increase in cardiac output, while all functional hemodynamic parameters decreased. A wide range of areas under the ROC-curve (AUC's) was observed: AUC SVVPiCCO = 0.91, AUC-PPVPiCCO = 0.88, AUC-SVVLiDCO = 0.78, AUC-PPVLiDCO = 0.89, AUC-SVVFloTrac = 0.87, AUC-PPVPhilips = 0.92 and AUC-PVI = 0.68. Optimal threshold values for prediction of fluid responsiveness ranged between 9.5 and 17.5%. Lowest threshold values were observed for SVVLiDCO, highest for PVI. CONCLUSION: All functional hemodynamic parameters tested except for PVI showed that their use allows a reliable identification of potential fluid responders. PVI however, may not be suitable after cardiac surgery to predict fluid responsiveness. TRIAL REGISTRATION: NCT02571465 , registered on October 7th, 2015 (retrospectively registered). PMID- 29788918 TI - Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation. AB - BACKGROUND: Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI2)-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. METHODS: BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI2-dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. RESULTS: As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI2 production. CONCLUSIONS: In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI2 pathway. PMID- 29788920 TI - A focus group study to understand biases and confounders in a cluster randomized controlled trial on low back pain in primary care in Norway. AB - BACKGROUND: Cluster randomized controlled trials are often used in research in primary care but creates challenges regarding biases and confounders. We recently presented a study on low back pain from primary care in Norway with equal effects in the intervention and the control group. In order to understand the specific mechanisms that may produce biases in a cluster randomized trial we conducted a focus group study among the participating health care providers. The aim of this study was to understand how the participating providers themselves influenced on the study and thereby possibly on the results of the cluster randomized controlled trial. METHODS: The providers were invited to share their experiences from their participation in the COPE study, from recruitment of patients to accomplishment of either the intervention or control consultations. Six clinicians from the intervention group and four from the control group took part in the focus group interviews. The group discussions focused on feasibility of the study in primary care and particularly on identifying potential biases and confounders in the study. The audio-recorded interviews were transcribed verbatim and analyzed according to a systematic text condensation. The themes for the analysis emerged from the group discussions. RESULTS: A personal interest for back pain, logistic factors at the clinics and an assessment of the patients' capacity to accomplish the study prior to their recruitment was reported. The providers were allowed to provide additional therapy to the intervention and it turned out that some of these could be regarded as opposed to the messages of the intervention. The providers seemed to select different items from the educational package according to personal beliefs and their perception of the patients' acceptance. CONCLUSION: The study disclosed several potential biases to the COPE study which may have impacted on the study results. Awareness of these is highly important when planning and conducting a cluster randomized controlled trial. Procedures in the recruitment of both providers and patients seem to be key factors and the providers should be aware of their role in a scientific study in order to standardize the provision of the intervention. PMID- 29788916 TI - In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters. AB - BACKGROUND: The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions. RESULTS: We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species. CONCLUSIONS: B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems. PMID- 29788923 TI - The segmentation of bones in pelvic CT images based on extraction of key frames. AB - BACKGROUND: Bone segmentation is important in computed tomography (CT) imaging of the pelvis, which assists physicians in the early diagnosis of pelvic injury, in planning operations, and in evaluating the effects of surgical treatment. This study developed a new algorithm for the accurate, fast, and efficient segmentation of the pelvis. METHODS: The proposed method consists of two main parts: the extraction of key frames and the segmentation of pelvic CT images. Key frames were extracted based on pixel difference, mutual information and normalized correlation coefficient. In the pelvis segmentation phase, skeleton extraction from CT images and a marker-based watershed algorithm were combined to segment the pelvis. To meet the requirements of clinical application, physician's judgment is needed. Therefore the proposed methodology is semi-automated. RESULTS: In this paper, 5 sets of CT data were used to test the overlapping area, and 15 CT images were used to determine the average deviation distance. The average overlapping area of the 5 sets was greater than 94%, and the minimum average deviation distance was approximately 0.58 pixels. In addition, the key frame extraction efficiency and the running time of the proposed method were evaluated on 20 sets of CT data. For each set, approximately 13% of the images were selected as key frames, and the average processing time was approximately 2 min (the time for manual marking was not included). CONCLUSIONS: The proposed method is able to achieve accurate, fast, and efficient segmentation of pelvic CT image sequences. Segmentation results not only provide an important reference for early diagnosis and decisions regarding surgical procedures, they also offer more accurate data for medical image registration, recognition and 3D reconstruction. PMID- 29788921 TI - Signatures of host specialization and a recent transposable element burst in the dynamic one-speed genome of the fungal barley powdery mildew pathogen. AB - BACKGROUND: Powdery mildews are biotrophic pathogenic fungi infecting a number of economically important plants. The grass powdery mildew, Blumeria graminis, has become a model organism to study host specialization of obligate biotrophic fungal pathogens. We resolved the large-scale genomic architecture of B. graminis forma specialis hordei (Bgh) to explore the potential influence of its genome organization on the co-evolutionary process with its host plant, barley (Hordeum vulgare). RESULTS: The near-chromosome level assemblies of the Bgh reference isolate DH14 and one of the most diversified isolates, RACE1, enabled a comparative analysis of these haploid genomes, which are highly enriched with transposable elements (TEs). We found largely retained genome synteny and gene repertoires, yet detected copy number variation (CNV) of secretion signal peptide containing protein-coding genes (SPs) and locally disrupted synteny blocks. Genes coding for sequence-related SPs are often locally clustered, but neither the SPs nor the TEs reside preferentially in genomic regions with unique features. Extended comparative analysis with different host-specific B. graminis formae speciales revealed the existence of a core suite of SPs, but also isolate specific SP sets as well as congruence of SP CNV and phylogenetic relationship. We further detected evidence for a recent, lineage-specific expansion of TEs in the Bgh genome. CONCLUSIONS: The characteristics of the Bgh genome (largely retained synteny, CNV of SP genes, recently proliferated TEs and a lack of significant compartmentalization) are consistent with a "one-speed" genome that differs in its architecture and (co-)evolutionary pattern from the "two-speed" genomes reported for several other filamentous phytopathogens. PMID- 29788922 TI - Galectin-3 activates TLR4/NF-kappaB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. AB - BACKGROUND: Lung cancer remains the top contributor to cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been reported to participate in normal development and tumorigenesis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is highly expressed in lung cancer and promotes lung cancer cell proliferation and migration. However, the upstream regulatory mechanism still needs investigation. METHODS: In the present study, we investigated the upstream regulators and mechanisms of NEAT1 expression disorders. We first examined NEAT1 expression in lung adenocarcinoma tissues and its correlation with clinic features in patient with lung adenocarcinoma; next, the detailed function of NEAT1 in lung cancer cell proliferation and migration was assessed. To investigate whether NF-kappaB acts as a transcription factor of NEAT1 to activate its expression, we validated the combination between NF-kappaB and NEAT1, and NF kappaB regulation of NEAT1 upon LPS stimulation. Further, the effect of NF-kappaB upstream regulator, TLR4, on NEAT1 expression upon LPS stimulation was examined. Galectin-3 reportedly serves as a ligand of TLR4 and promotes TLR4, MyD88 and p p65 expression; we investigated whether Galectin-3 could modulate lung adenocarcinoma cell proliferation and migration through TLR4/NF-kappaB/NEAT1. Finally, the expression and correlation of the above factors in lung adenocarcinoma tissues was validated. RESULTS: NEAT1 is highly expressed in lung adenocarcinoma tissues and promotes lung cancer cell proliferation and migration. NF-kappaB binds to NEAT1 promoter to activate NEAT1 expression after LPS stimulated p65 nucleus translocation. LPS stimulation activates TLR4 signaling, followed by downstream NF-kappaB activation, and ultimately NEAT1 expression activation. Galectin-3 activates TLR4 signaling thus affecting lung cancer cell proliferation and migration through TLR4/NF-kappaB/NEAT1. Galectin-3 and TLR4 expression are abnormally up-regulated in lung adenocarcinoma tissues, and positively correlated with NEAT1 expression. CONCLUSION: We confirmed that Galectin-3 as a ligand of TLR4 induced TLR4 signaling activation in lung adenocarcinoma cells, thereby activating downstream p65 nucleus translocation, promoting NEAT1 expression, and finally affecting lung adenocarcinoma cell proliferation and migration. Inhibiting Galectin-3-induced TLR4 signaling activation, thus to reduce p65-activated NEAT1 expression might be a promising strategy of suppressing lung adenocarcinoma cell proliferation and migration. PMID- 29788924 TI - Exploration of the association between FOXE1 gene polymorphism and differentiated thyroid cancer: a meta-analysis. AB - BACKGROUND: Several association analyses and linkage researches indicated that inherited genetic variations effectively influence differentiated thyroid carcinogenesis. METHODS: The results from 15 published studies on differentiated thyroid carcinoma (DTC) were combined. The genetic model included rs965513, rs944289 and rs1867277. Meta-analyses were performed and cochran's chi2 based Q statistic and I2 test were performed to assess heterogeneity using STATA software. RESULTS: Significant results were noticed for rs965513(Odds Ratio(OR) = 1.162(1.117, 1.208)), rs944289(OR = 1.082(1.035, 1.131)) and rs1867277(OR = 1.415(1.324, 1.512)). In the subgroup analysis by ethnicity, rs965513 polymorphism conferred that risk of Caucasians (OR = 1.168(1.122, 1.215)) was more than that of East Asians of 1.35 (OR = 0.897(0.680, 1.193)). CONCLUSION: This meta-analysis revealed that common variations of FOXE1 (rs965513, rs944289 and rs1867277) were risk factors associated with increased DTC susceptibility. PMID- 29788927 TI - Chronic Kirschsteiniothelia infection superimposed on a pre-existing non infectious bursitis of the ankle: the first case report of human infection. AB - BACKGROUND: Kirschsteiniothelia is a saprophytic fungus that is abundantly present in the environment. To date, there have been no reports of human infection caused by this fungus. We report a case of Kirschsteiniothelia infection superimposed on a pre-existing non-infectious bursitis of the ankle. CASE PRESENTATION: An 81-year-old immunocompetent female local farmer noticed the presence of a nodule on her right ankle 5 years before her first visit to our hospital. A cystic mass of approximately 45 mm * 30 mm was present at the tip of the right lateral malleolus. Culture of the aspirated fluid revealed visibly black colonies and characteristic blackish hyphae; nucleotide sequence of the internal transcribed spacer region was determined and compared in a GenBank database. The results indicated Kirschsteiniothelia infection. CONCLUSIONS: We described the first case of Kirschsteiniothelia infection manifested as ankle bursitis. The disease seemed to be localized and systemic antibiotics had not been used in this case. However, continued observation is needed because of the possibility of disease progression with the pathogen. PMID- 29788925 TI - De novo transcriptome assembly of the eight major organs of Sacha Inchi (Plukenetia volubilis) and the identification of genes involved in alpha linolenic acid metabolism. AB - BACKGROUND: Sacha Inchi (Plukenetia volubilis L.), which belongs to the Euphorbiaceae, has been considered a new potential oil crop because of its high content of polyunsaturated fatty acids in its seed oil. The seed oil especially contains high amounts of alpha-linolenic acid (ALA), which is useful for the prevention of various diseases. However, little is known about the genetic information and genome sequence of Sacha Inchi, which has largely hindered functional genomics and molecular breeding studies. RESULTS: In this study, a de novo transcriptome assembly based on transcripts sequenced in eight major organs, including roots, stems, shoot apexes, mature leaves, male flowers, female flowers, fruits, and seeds of Sacha Inchi was performed, resulting in a set of 124,750 non-redundant putative transcripts having an average length of 851 bp and an N50 value of 1909 bp. Organ-specific unigenes analysis revealed that the most organ-specific transcripts are found in female flowers (2244 unigenes), whereas a relatively small amount of unigenes are detected to be expressed specifically in other organs with the least in stems (24 unigenes). A total of 42,987 simple sequence repeats (SSRs) were detected, which will contribute to the marker assisted selection breeding of Sacha Inchi. We analyzed expression of genes related to the alpha-linolenic acid metabolism based on the de novo assembly and annotation transcriptome in Sacha Inchi. It appears that Sacha Inchi accumulates high level of ALA in seeds by strong expression of biosynthesis-related genes and weak expression of degradation-related genes. In particular, the up-regulation of FAD3 and FAD7 is consistent with high level of ALA in seeds of Sacha Inchi compared with in other organs. Meanwhile, several transcription factors (ABI3, LEC1 and FUS3) may regulate key genes involved in oil accumulation in seeds of Sacha Inchi. CONCLUSIONS: The transcriptome of major organs of Sacha Inchi has been sequenced and de novo assembled, which will expand the genetic information for functional genomic studies of Sacha Inchi. In addition, the identification of candidate genes involved in ALA metabolism will provide useful resources for the genetic improvement of Sacha Inchi and the metabolic engineering of ALA biosynthesis in other plants. PMID- 29788926 TI - Correlation of increased corrected TIMI frame counts and the topographical extent of isolated coronary artery ectasia. AB - BACKGROUND: The precise relationship between increased thrombolysis in myocardial infarction (TIMI) frame counts and the topographical extent of isolated coronary artery ectasia (CAE) has not been fully explained. New parameters of linear dimension (LD) and the estimated ectatic area (EEA) together with the diameter and ectasia ratio may be associated with the corrected TIMI frame count (CTFC) in isolated CAE patients. METHODS: The topographical parameters of ectatic coronary arteries and/or segments of 77 isolated CAE patients were consecutively studied. The CTFC for each coronary artery was determined by angiographic frame count. RESULTS: Right coronary artery (RCA) was the most frequently affected. The RCA and left circumflex (LCX) had significantly longer LD (p < 0.001 for both), and greater EEA (p < 0.001 for both) than those of left anterior descending artery (LAD). Similarly, the RCA and LCX have higher CTFCs (p = 0.001 and p = 0.008, respectively) than LAD. All topographic parameters and CTFCs were positively correlated with Markis classification. Linear regression analyses revealed that CTFCs were strongly correlated with diameter, LD, ectasia ratio and EEA, while EEA was the best predictor for the CTFC. Among multiple linear and nonlinear regression models, the cubic model between the CTFC and EEA exhibits the best Goodness-of-Fit. CONCLUSION: The severity of the topographical extent of CAE was significantly correlated with increased CTFCs. Both the linear dimension and ectatic diameter (combined as EEA) were important for evaluating decreased coronary flow in isolated CAE patients. PMID- 29788928 TI - Residents' breastfeeding knowledge, comfort, practices, and perceptions: results of the Breastfeeding Resident Education Study (BRESt). AB - BACKGROUND: Physicians have a significant impact on new mothers' breastfeeding practices. However, physicians' breastfeeding knowledge is suboptimal. This knowledge deficit could be the result of limited breastfeeding education in residency. This study aimed to explore pediatric residents' breastfeeding knowledge, comfort level, clinical practices, and perceptions. It also investigated the level and type of education residents receive on breastfeeding and their preferences for improving it. METHODS: Descriptive, cross-sectional, self-reported online questionnaires were sent to all residents enrolled in a Canadian general pediatric residency program, as well as to their program directors. Resident questionnaires explored breastfeeding knowledge, comfort level, clinical practices, perceptions, educational experiences and educational preferences. Program director questionnaires collected data on current breastfeeding education in Canadian centers. For the resident survey, breastfeeding knowledge was calculated as the percent of correct responses. Demographic factors independently associated with overall knowledge score were identified by multiple linear regression. Descriptive statistics were used for the program director survey. RESULTS: Overall, 201 pediatric residents, and 14 program directors completed our surveys. Residents' mean overall breastfeeding knowledge score was 71% (95% CI: 69-79%). Only 4% (95% CI: 2-8%) of residents were very comfortable evaluating latch, teaching parents breastfeeding positioning, and addressing parents' questions regarding breastfeeding difficulties. Over a quarter had not observed a patient breastfeed. Nearly all agreed or strongly agreed that breastfeeding promotion is part of their role. Less than half reported receiving breastfeeding education during residency and almost all wanted more interactive breastfeeding education. According to pediatric program directors, most of the breastfeeding education residents receive is didactic. Less than a quarter of program directors felt that the amount of breastfeeding education provided was adequate. CONCLUSION: Pediatric residents in Canada recognize that they play an important role in supporting breastfeeding. Most residents lack the knowledge and training to manage breastfeeding difficulties but are motivated to learn more about breastfeeding. Pediatric program directors recognize the lack of breastfeeding education. PMID- 29788930 TI - NPBSS: a new PacBio sequencing simulator for generating the continuous long reads with an empirical model. AB - BACKGROUND: PacBio sequencing platform offers longer read lengths than the second generation sequencing technologies. It has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. Due to its extremely wide range of application areas, fast sequencing simulation systems with high fidelity are in great demand to facilitate the development and comparison of subsequent analysis tools. Although there are several available simulators (e.g., PBSIM, SimLoRD and FASTQSim) that target the specific generation of PacBio libraries, the error rate of simulated sequences is not well matched to the quality value of raw PacBio datasets, especially for PacBio's continuous long reads (CLR). RESULTS: By analyzing the characteristic features of CLR data from PacBio SMRT (single molecule real time) sequencing, we developed a new PacBio sequencing simulator (called NPBSS) for producing CLR reads. NPBSS simulator firstly samples the read sequences according to the read length logarithmic normal distribution, and choses different base quality values with different proportions. Then, NPBSS computes the overall error probability of each base in the read sequence with an empirical model, and calculates the deletion, substitution and insertion probabilities with the overall error probability to generate the PacBio CLR reads. Alignment results demonstrate that NPBSS fits the error rate of the PacBio CLR reads better than PBSIM and FASTQSim. In addition, the assembly results also show that simulated sequences of NPBSS are more like real PacBio CLR data. CONCLUSION: NPBSS simulator is convenient to use with efficient computation and flexible parameters setting. Its generating PacBio CLR reads are more like real PacBio datasets. PMID- 29788929 TI - Resveratrol induces autophagy-dependent apoptosis in HL-60 cells. AB - BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student's unpaired t test. RESULTS: We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. CONCLUSIONS: These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways. PMID- 29788931 TI - The prevalence of substance use among Russian, Somali and Kurdish migrants in Finland: a population-based study. AB - BACKGROUND: Substance use is a well-known public health problem, but population based research on migrants' substance use in Europe is limited. Factors related to the cultural background and current life situation might influence substance use among migrants. Here, the prevalence of substance use in Russian, Somali and Kurdish migrants in Finland is reported in comparison with the general population, and the associations between substance use and socio-economic and migration-related background factors among migrants are analysed. METHODS: Cross sectional data from the Finnish Migrant Health and Wellbeing Study (Maamu) and comparison group data of the general Finnish population (n = 1165) from the Health 2011 Survey were used. The survey participants were of Russian (n = 702), Somali (n = 512), and Kurdish (n = 632) origin. Substance use included self reported alcohol use within previous 12 months (AUDIT-C questionnaire), current and lifetime daily smoking and lifetime use of cannabis and intravenous drugs. RESULTS: Binge drinking was less prevalent among all migrant groups than in the general Finnish population (Russian men 65%, p < 0.01; Russian women 30%, p < 0.01, Somali men 2%, p < 0.01, Kurdish men 27%, p < 0.01, Kurdish women 6%, p < 0.01, general population men 87% and women 72%). Current daily smoking was more prevalent among Russian (28%, p = 0.04) and Kurdish (29%, p < 0.01) migrant men compared with the reference group (20%). Younger age and employment were associated with binge drinking among migrants. Socio-economic disadvantage increased the odds for daily smoking in Russian, Somali and Kurdish migrant men. Several migration-related factors, such as age at migration and language proficiency, were associated with substance use. CONCLUSIONS: Binge drinking is less common among migrants than in the Finnish general population. However, current daily smoking was more prevalent among Russian and Kurdish migrant men compared with the general population. Younger age, level of education, employment, duration of residence in Finland and language proficiency were associated with binge drinking and daily smoking with varying patterns of association depending on the migrant group and gender. These findings draw attention to the variation in substance use habits among migrant populations. PMID- 29788934 TI - The lung microbiome in children with HIV-bronchiectasis: a cross-sectional pilot study. AB - BACKGROUND: Data on the lung microbiome in HIV-infected children is limited. The current study sought to determine the lung microbiome in HIV-associated bronchiectasis and to assess its association with pulmonary exacerbations. METHODS: A cross-sectional pilot study of 22 children (68% male; mean age 10.8 years) with HIV-associated bronchiectasis and a control group of 5 children with cystic fibrosis (CF). Thirty-one samples were collected, with 11 during exacerbations. Sputum samples were processed with 16S rRNA pyrosequencing. RESULTS: The average number of operational taxonomy units (OTUs) was 298 +/- 67 vs. 434 +/- 90, for HIV-bronchiectasis and CF, respectively. The relative abundance of Proteobacteria was higher in HIV-bronchiectasis (72.3%), with only 22.2% Firmicutes. There was no correlation between lung functions (FEV1% and FEF25/75%) and bacterial community (r = 0.154; p = 0.470 and r = 0.178; p = 0.403), respectively. Bacterial assemblage of exacerbation and non-exacerbation samples in HIV-bronchiectasis was not significantly different (ANOSIM, RHIV bronchiectasis = 0.08; p = 0.14 and RCF = 0.08, p = 0.50). Higher within community heterogeneity and lower evenness was associated with CF (Shannon-Weiner (H') = 5.39 +/- 0.38 and Pielou's evenness (J) 0.79 +/- 0.10 vs. HIV bronchiectasis (Shannon-Weiner (H') = 4.45 +/- 0.49 and Pielou's (J) 0.89 +/- 0.03. CONCLUSION: The microbiome in children with HIV-associated bronchiectasis seems to be less rich, diverse and heterogeneous with predominance of Proteobacteria when compared to cystic fibrosis. PMID- 29788933 TI - Continue, adjust, or stop antipsychotic medication: developing and user testing an encounter decision aid for people with first-episode and long-term psychosis. AB - BACKGROUND: People with psychosis struggle with decisions about their use of antipsychotics. They often want to reduce the dose or stop, while facing uncertainty regarding the effects these decisions will have on their treatment and recovery. They may also fear raising this issue with clinicians. The purpose of this study was to develop and test a shared decision making (SDM) tool to support patients and clinicians in making decisions about antipsychotics. METHODS: A diverse editorial research team developed an Encounter Decision Aid (EDA) for patients and clinicians to use as part of the psychiatric consultation. The EDA was tested using 24 semistructured interviews with participants representing six stakeholder groups: patients with first-episode psychosis, patients with long-term psychosis, family members, psychiatrists, mental health counselors, and administrators. We used inductive and deductive coding of interview transcripts to identify points to revise within three domains: general impression and purpose of the EDA; suggested changes to the content, wording, and appearance; and usability and potential contribution to the psychiatric consultation. RESULTS: An EDA was developed in an iterative process that yielded evidence-based answers to five frequently asked questions about antipsychotic medications. Patients with long-term psychosis and mental health counselors suggested more changes and revisions than patients with first-episode psychosis and psychiatrists. Family members suggested more revisions to the answers about potential risks of stopping or adjusting antipsychotics than other respondents. CONCLUSIONS: The EDA was perceived as potentially useful and feasible in psychiatric routine care, especially if presented during the consultation. PMID- 29788935 TI - Maternal anemia is a potential risk factor for anemia in children aged 6-59 months in Southern Africa: a multilevel analysis. AB - BACKGROUND: The effect of maternal anemia on childhood hemoglobin status has received little attention. Thus, we examined the potential association between maternal anemia and childhood anemia (aged 6-59 months) from selected Southern Africa countries. METHODS: A cross-sectional study using nationally representative samples of children aged 6-59 months from the 2010 Malawi, 2011 Mozambique, 2013 Namibia, and 2010-11 Zimbabwe demographic and health surveys (DHS) was conducted. Generalized linear mixed models (GLMMs) were constructed to test the associations between maternal anemia and childhood anemia, controlling for individual and community sociodemographic covariates. RESULTS: The GLMMs showed that anemic mothers had increased odds of having an anemic child in all four countries; adjusted odds ratio (aOR = 1.69 and 95% confidence interval [CI]:1.37-2.13) in Malawi, (aOR = 1.71; 95% CI: 1.37-2.13) in Mozambique, (aOR = 1.55; 95% CI: 1.08-2.22) in Namibia, and (aOR = 1.52; 95% CI: 1.25-1.84) in Zimbabwe. Furthermore, the odds of having an anemic child was higher in communities with a low percentage of anemic mothers (aOR = 1.52; 95% CI: 1.19 1.94) in Mozambique. CONCLUSIONS: Despite the long-standing efforts to combat childhood anemia, the burden of this condition is still rampant and remains a significant problem in Southern Africa. Thus, public health strategies aimed at reducing childhood anemia should focus more on addressing infections, and micronutrient deficiencies both at individual and community levels in Southern Africa. PMID- 29788932 TI - Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. AB - Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis. PMID- 29788937 TI - Seroprevalence of transfusion-transmissible infections (HBV, HCV, syphilis and HIV) among prospective blood donors in a tertiary health care facility in Calabar, Nigeria; an eleven years evaluation. AB - BACKGROUND: Provision of constant and safe blood has been a public health challenge in Sub-Saharan Africa with high prevalence of transfusion-transmissible infections (TTIs). This study was aimed at determining the trend and seroprevalence of HBV, HCV, syphilis and HIV across the years within study among prospective blood donors at blood bank in University of Calabar Teaching Hospital (UCTH), Calabar, Nigeria. METHODS: A retrospective analysis of blood donor data from January 2005 to December 2016 was conducted in Blood Bank/Donor Clinic of University of Calabar Teaching Hospital, Calabar, Nigeria. Sera samples were screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (HCV), human immunodeficiency virus (HIV) 1 and 2 and Treponema pallidum using commercially available immunochromatic based kits. RESULTS: Out of the 24,979 screened prospective donors in the 2005-2016 study period, 3739 (14.96%) were infected with at least one infective agent. The overall prevalence of HBV, HCV, syphilis and HIV were 4.1, 3.6, 3.1 and 4.2%, respectively. During the period of study, the percentage of all transfusion-transmissible infections declined significantly with remarkable decline in HIV. The study showed male dominated donor pool (98.7%) with higher prevalence (4.2%) of transfusion-transmissible infections than in female donors (0.0%). Commercial donors constituted majority (62.0%) of the donors and as well had the highest prevalence of transfusion transmissible infections. Majority (62.9%) of the donors were repeat donors. CONCLUSION: HBV, HCV, syphilis and HIV have remained a big threat to safe blood transfusion in Nigeria and Sub-Saharan Africa at large. Strict adherence to selection criteria and algorithm of donor screening are recommended. PMID- 29788936 TI - Association between stress fracture incidence and predicted body fat in United States Army Basic Combat Training recruits. AB - BACKGROUND: A stress fracture (SF) is a highly debilitating injury commonly experienced in United States Army Basic Combat Training (BCT). Body fat (BF) may be associated with this injury but previous investigations (in athletes) have largely used SF self-reports and lacked sufficient statistical power. This investigation developed an equation to estimate %BF and used that equation to examine the relationship between %BF and SF risk in BCT recruits. METHODS: Data for the %BF predictive equation involved 349 recruits with BF obtained from dual energy X-ray absorptiometry. %BF was estimated using body mass index (BMI, weight/height2), age (yr), and sex in the entire population of BCT recruits over an 11-year period (n = 583,651). Medical information was obtained on these recruits to determine SF occurrence. Recruits were separated into deciles of estimated %BF and the risk of SFs determined in each decile. RESULTS: The equation was %BF = - 7.53 + 1.43 ? BMI + 0.13 ? age - 14.73 ? sex, with sex either 1 for men or 0 for women (r = 0.88, standard error of estimate = 4.2%BF). Among the men, SF risk increased at the higher and lower %BF deciles: compared to men in the mean %BF decile, the risk of a SF for men in the first (lowest %BF) and tenth (highest %BF) decile were 1.27 (95%confidence interval (95%CI) = 1.17 1.40) and 1.15 (95%CI = 1.05-1.26) times higher, respectively. Among women, SF risk was only elevated in the first %BF decile with risk 1.20 (95%CI = 1.09-1.32) times higher compared to the mean %BF decile. CONCLUSIONS: Low %BF was associated with higher SF risk in BCT; higher %BF was associated with higher SF risk among men but not women. PMID- 29788938 TI - Symptom prevalence of patients with fibrotic interstitial lung disease: a systematic literature review. AB - BACKGROUND: Those affected by advanced fibrotic interstitial lung diseases have limited treatment options and in the terminal stages, the focus of care is on symptom management. However, quantitatively, little is known about symptom prevalence. We aimed to determine the prevalence of symptoms in Progressive Idiopathic Fibrotic Interstitial Lung Disease (PIF-ILD). METHODS: Searches on eight electronic databases including MEDLINE for clinical studies between 1966 and 2015 where the target population was adults with PIF-ILD and for whom the prevalence of symptoms had been calculated. RESULTS: A total of 4086 titles were screened for eligibility criteria; 23 studies were included for analysis. The highest prevalence was that for breathlessness (54-98%) and cough (59-100%) followed by heartburn (25-65%) and depression (10-49%). The heterogeneity of studies limited their comparability, but many of the symptoms present in patients with other end-stage disease were also seen in PIF-ILD. CONCLUSIONS: This is the first quantitative review of symptoms in people with Progressive Idiopathic Fibrotic Interstitial Lung Diseases. Symptoms are common, often multiple and have a comparable prevalence to those experienced in other advanced diseases. Quantification of these data provides valuable information to inform the allocation of resources. PMID- 29788939 TI - NonTuberculous Mycobacteria infection and lung transplantation in cystic fibrosis: a worldwide survey of clinical practice. AB - BACKGROUND: In people with cystic fibrosis infection with NonTuberculous Mycobacteria is of increasing prevalence. Mycobacterium abscessus complex is of particular concern and has been associated with adverse clinical outcomes. Optimal treatment usually requires multiple antibiotics for over 12 months. When considering lung transplantation for patients with NonTuberculous Mycobacteria potential benefits must be balanced against the risks of uncontrolled infection post-transplant and significant side-effects associated with treatment. In this survey we assessed current international practice with regard to assessing and listing patients for lung transplantation. METHODS: We designed a questionnaire enquiring about local practice regarding screening for NonTuberculous Mycobacteria infection, specific contra-indications to transplantation, management and segregation of patients pre- and post-transplant. The survey was sent via e-mail to 37 paediatric and adult lung transplant centres across Europe, North America and Australia. RESULTS: We gathered complete questionnaires from 21 centres (57% response rate). Few centres (29%) have a clear written policy regarding NonTuberculous Mycobacteria. Sixteen (76%) centres require molecular identification of NonTuberculous Mycobacteria species. Only four centres would consider infection with M. abscessus complex in itself a contra-indication for listing, however 76% regard it as a relative contra-indication. Eighty-six percent require treatment pre-transplantation. Finally, only 61% of centres had a clear policy regarding segration of patients pre-transplant and 48% post transplant. CONCLUSIONS: The issue of NonTuberculous Mycobacteria infection in people with cystic fibrosis requiring lung transplantation is well-recognized however current international recommendations are not detailed and there is variation in practice between centres. There is an urgent requirement for high quality clinical data to inform decision-making. PMID- 29788940 TI - Two cases in which 3D MRI was used to differentiate between a disc mass that mimics a tumor and neurinoma. AB - BACKGROUND: Since disc sequestration that mimics a tumor is rare and sometimes presents with an atypical appearance upon magnetic resonance imaging (MRI), it is often confused with other more common epidural and intradural neoplasms, particularly neurinoma. Open surgery is necessary due to the difficult of achieving a definitive diagnosis using computed tomography, MRI, and gadolinium- enhanced MRI prior to operation. Herein, we describe the use of coronal MR images of 3D fast-field echo with water selective excitation in the diagnosis of disc sequestration mimicking a tumor. CASE PRESENTATION: Two patients were admitted to our hospital with back pain, radiating pain, and hypoesthesia in the right lower limb. MRI revealed tumor-like masses in the lateral recess of L3 and posterior to the body of L4. The initial diagnosis indicated disc sequestration mimicking a tumor and neurinoma. The coronal MR images of 3D fast-field echo with water selective excitation showed a clear boundary between the tumor-like mass and the nerve root. Moreover, the mass was also completely separated from the dura. Therefore, neurinoma was excluded as a possible diagnosis prior to operation. Surgical excision to perform removal of the gross mass was performed in one patient. The histopathological diagnosis was consistent with the 3D fast-field echo with water-selective excitation MRI. Another patient was successfully treated by minimally invasive endoscopic surgery. CONCLUSIONS: Disc sequestration that mimics a tumor is difficult to diagnose preoperatively. As a non-invasive strategy, coronal MR images of 3D fast-field echo with water selective excitation is a helpful imaging tool for differentiating between diagnosis of disc sequestration that mimics a tumor and neurinoma prior to operation. If the disc fragment of mimicking tumor can be identified prior to operation, open surgery may not be necessary for all patients. Minimally invasive endoscopic surgery also is an alternative strategy. PMID- 29788941 TI - Are we really "eating well with Canada's food guide"? AB - BACKGROUND: Canada's Food Guide (CFG) has been an important health promotion tool for over seventy years. The most recent version was released in 2007. This study examined Canadians' exposure to, knowledge, and use of CFG. METHODS: Data came from the Canadian Community Health Survey's Rapid Response on the Awareness and Usage of Canada's Food Guide, which included 10,098 Canadians >=12 y in all ten provinces. Questions were asked on familiarity, awareness and usage of CFG and Canada's Food Guide for First Nations, Inuit and Metis, as well as healthy eating principles and behaviours. Descriptive statistics and logistic regression were used to observe counts and differences among key demographic variables. RESULTS: More than 80% of Canadians have heard of CFG however significantly more women than men were aware of the Guide. Most knew that 'Vegetables and Fruit' had the most recommended servings and that dark green vegetables should be consumed daily; however fewer than half knew this of orange vegetables. Just under one third had a copy in their homes, and the most common sources for obtaining CFG were child's school and health professional/trainer. Those who consulted CFG recently were more likely to consume the recommended servings of vegetables and fruits, and to state that their eating habits were 'much better' than one year previously. CONCLUSIONS: CFG has "brand recognition" among Canadians however there are gaps between awareness and eating behaviours. The new Food Guide could consider additional dissemination tools including social media, videos and workbooks tailored to various age groups, demographic groups and settings. PMID- 29788942 TI - Use of autologous bone marrow stem cell implantation for osteonecrosis of the knee in sickle cell disease: a preliminary report. AB - BACKGROUND: The purpose of our study was to evaluate safety, feasibility and clinical results of bone marrow mononuclear cell (BMC) implantation for early stage osteonecrosis of the knee (OK) secondary to sickle cell disease. METHODS: Thirty-three SCD patients (45 knees) with OK treated with BMC implantation in the osteonecrotic lesion were clinically and functionally evaluated through the American Knee Society Clinical Score (KSS), Knee Functional Score (KFS) and Numeric Rating Scale (NRS) pain score. MRI and radiographic examinations of the knee were assessed during a period of five years after intervention. RESULTS: No complications or serious adverse event were associated with BMC implantation. From preoperative assessment to the latest follow-up, there was a significant (p < 0.001) improvement of clinical KSS (64.3 +/- 9.7, range: 45-80 and 2.2 +/- 4.1, range: 84-100, respectively), KFS (44.5 +/- 8.0, range: 30-55 and 91.6 +/- 5.8, range: 80-100, respectively) and reduction of NRS pain score (6.7 +/- 1.2, range: 4-9 and 3.4 +/- 1.0, range: 2-5, respectively). In total, 87% of patients (29/33) consistently experienced improvements in joint function and activity level as compared to preoperative score. No patient had additional surgery following BMC implantation. Radiographic assessment showed joint preservation and no progression to subchondral collapse at most recent follow-up. CONCLUSIONS: The technique of BMC implantation is a promising, relatively simple and safe procedure for OK in SCD patients. Larger and long-term controlled trials are needed to support its clinical effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT02448121 . Retrospectively registered 19 May 2015. PMID- 29788944 TI - Bronchiectasis: an emerging global epidemic. AB - Bronchiectasis has an increasing profile within respiratory medicine. This chronic and irreversible airways disease is common but suffers from a lack of evidenced based therapy for patients and, a lack of understanding of its inherent heterogeneity. Research focused on bronchiectasis must therefore be prioritized if we are to adequately address this evolving clinical problem. This special issue on bronchiectasis focuses on its clinical, microbiological and therapeutic aspects. By bringing together a unique collection of original research and review articles, we hope this issue will showcase international research efforts, encourage future research collaborations and stimulate debate. In doing so, we hope to bring greater attention to the urgent need for sustained investment into focused, dedicated and collaborative research platforms in bronchiectasis, an emerging "global epidemic". PMID- 29788943 TI - Profiling non-tuberculous mycobacteria in an Asian setting: characteristics and clinical outcomes of hospitalized patients in Singapore. AB - BACKGROUND: Non-tuberculous mycobacteria (NTM) infection is an increasing problem worldwide. The epidemiology of NTM in most Asian countries is unknown. This study investigated the epidemiology, and clinical profile of inpatients in whom NTM was isolated from various anatomical sites in a Singaporean population attending a major tertiary referral centre. METHODS: Demographic profile, clinical data, and characteristics of patients hospitalized with NTM isolates at a major tertiary hospital over two-year period were prospectively assessed (2011-2012). Data collected included patient demographics, ethnicity, smoking status, co morbidities, NTM species, intensive care unit (ICU) treatment, and mortality. RESULTS: A total of 485 patients (62.1% male) with 560 hospital admissions were analysed. The median patient age was 70 years. Thirteen different NTM species were isolated from this cohort. Mycobacterium abscessus (M. abscessus) (38.4%) was most frequently isolated followed by Mycobacterium fortuitum (M. fortuitum) (16.6%), Mycobacterium avium complex (MAC) (16.3%), Mycobacterium kansasii (M. kansasii) (15.4%), and Mycobacterium gordonae (M. gordonae) (6.8%). Most (91%) NTM was isolated from the respiratory tract. The three most common non-pulmonary sites were; blood (2.7%), skin wounds and abscesses (2.1%), and gastric aspirates (1.1%). A third (34.4%) of the study population had prior pulmonary tuberculosis (PTB). There was a significant association between isolated NTM species, and patient age (p = 0.0002). Eleven (2.2%) patients received intensive care unit (ICU) treatment during the study period and all cause mortality within 1 year of the study was 16.9% (n = 82). Of these, 72 (87.8%) patients died of pulmonary causes. CONCLUSIONS: The profile of NTM species in Singapore is unique. M. abscessus is the commonest NTM isolated, with a higher prevalence in males, and in the elderly. High NTM prevalence is associated with high rates of prior PTB in our cohort. PMID- 29788945 TI - Musculoskeletal disorders among preschool teachers: analyzing the relationships among relational demands, work meaning, and intention to leave the job. AB - BACKGROUND: Based on the conservation of resource (COR) theory by Hobfoll, the aim of the present study was to test whether the relationships among relational demands, work meaning, and intention to leave vary as a function of the presence of musculoskeletal disorders (MSDs). METHOD: The study was cross-sectional and non-randomized. Analyses were carried out on a dataset consisting of 429 preschool teachers, who filled out a self-report questionnaire. Of them, 238 reported a MSD diagnosis and 191 were free form MSDs. RESULTS: As expected, among those who reported MSDs, relational demands were significantly associated to intention to leave, and this relationship was mediated by work meaning; moreover, among those free from MSDs, no significant paths among the three variables were found. CONCLUSION: In general, results showed that suffering from MSDs impairs workers' ability to face to relational demands, thus activating a spiral that encompasses diminished work meaning and intention to leave. Practical implications of results will be discussed in the paper. PMID- 29788947 TI - Electronic Health Record (EHR)-Based Community Health Measures: An Exploratory Assessment of Perceived Usefulness by Local Health Departments. AB - BACKGROUND: Given the widespread adoption of electronic health record (EHR) systems in health care organizations, public health agencies are interested in accessing EHR data to improve health assessment and surveillance. Yet there exist few examples in the U.S. of governmental health agencies using EHR data routinely to examine disease prevalence and other measures of community health. The objective of this study was to explore local health department (LHD) professionals' perceptions of the usefulness of EHR-based community health measures, and to examine these perceptions in the context of LHDs' current access and use of sub-county data, data aggregated at geographic levels smaller than county. METHODS: To explore perceived usefulness, we conducted an online survey of LHD professionals in Indiana. One hundred and thirty-three (133) individuals from thirty-one (31) LHDs participated. The survey asked about usefulness of specific community health measures as well as current access to and uses of sub county population health data. Descriptive statistics were calculated to examine respondents' perceptions, access, and use. A one-way ANOVA (with pairwise comparisons) test was used to compare average scores by LHD size. RESULTS: Respondents overall indicated moderate agreement on which community health measures might be useful. Perceived usefulness of specific EHR-based community health measures varied by size of respondent's LHD [F(3, 88) = 3.56, p = 0.017]. Over 70% of survey respondents reported using community health data, but of those < 30% indicated they had access to sub-county level data. CONCLUSION: Respondents generally preferred familiar community health measures versus novel, EHR-based measures that are not in widespread use within health departments. Access to sub county data is limited but strongly desired. Future research and development is needed as LHD staff gain access to EHR data and apply these data to support the core function of health assessment. PMID- 29788946 TI - Patient information, education and self-management in bronchiectasis: facilitating improvements to optimise health outcomes. AB - BACKGROUND: Bronchiectasis is an incurable lung disease characterised by irreversible airway dilatation. It causes symptoms including chronic productive cough, dyspnoea, and recurrent respiratory infections often requiring hospital admission. Fatigue and reductions in quality of life are also reported in bronchiectasis. Patients often require multi-modal treatments that can be burdensome, leading to issues with adherence. In this article we review the provision of, and requirement for, education and information in bronchiectasis. DISCUSSION: To date, little research has been undertaken to improve self management in bronchiectasis in comparison to other chronic conditions, such as COPD, for which there has been a wealth of recent developments. Qualitative work has begun to establish that information deficit is one of the potential barriers to self-management, and that patients feel having credible information is fundamental when learning to live with and manage bronchiectasis. Emerging research offers some insights into ways of improving treatment adherence and approaches to self-management education; highlighting ways of addressing the specific unmet information needs of patients and their families who are living with bronchiectasis. CONCLUSIONS: We propose non-pharmacological recommendations to optimise patient self-management and symptom recognition; with the aim of facilitating measurable improvements in health outcomes for patients with bronchiectasis. PMID- 29788948 TI - GeneChip analysis of resistant Mycobacterium tuberculosis with previously treated tuberculosis in Changchun. AB - BACKGROUND: With the widespread use of rifampicin and isoniazid, bacterial resistance has become a growing problem. Additionally, the lack of relevant baseline information for the frequency of drug-resistant tuberculosis (TB) gene mutations is a critical issue, and the incidence of this infection in the city of Changchun has not investigated to date. However, compared with the slow traditional methods of drug susceptibility testing, recently developed detection methods, such as rifampicin and isoniazid resistance-related gene chip techniques, allow for rapid, easy detection and simultaneous testing for mutation frequency and drug resistance. METHODS: In this study, the rifampicin and isoniazid resistance-related gene mutation chip method was employed for an epidemiological investigation. To assess the gene mutation characteristics of drug-resistant TB and evaluate the chip method, we tested 2143 clinical specimens from patients from the infectious diseases hospital of Changchun city from January to December 2016. The drug sensitivity test method was used as the reference standard. RESULTS: The following mutation frequencies of sites in the rifampicin resistance gene rpoB were found: Ser531Leu (52.6%), His526Tyr (12.3%), and Leu511Pro (8.8%). The multidrug-resistance (MDR)-TB mutation frequency was 34.7% for rpoB Ser531Leu and katG Ser315Thr, 26.4% for rpoB Ser531Leu and inhA promoter - 15 (C -> T), and 10.7% for rpoB His526Tyr and katG Ser315Thr. In addition, drug susceptibility testing served as a reference standard. In previously treated clinical cases, the sensitivity and specificity of GeneChip were 83.1 and 98.7% for rifampicin resistance, 79.9 and 99.6% for isoniazid resistance, and 74.1 and 99.8% for MDR-TB. CONCLUSIONS: Our experimental results show that the chip method is accurate and reliable; it can be used to detect the type of drug-resistant gene mutation in clinical specimens. Moreover, this study can be used as a reference for future research on TB resistance baselines. PMID- 29788949 TI - Range of motion after total knee arthroplasty in hemophilic arthropathy. AB - BACKGROUND: Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as infection and an unsatisfactory range of motion, which have influenced the survival of prostheses. Our retrospective study evaluated the data of hemophilic patients regarding changes in the development of the range of motion. METHODS: The data and clinical outcomes of 72 total knee replacements in 45 patients with hemophilia types A and B were reviewed retrospectively. Patients were operated between 1998 and 2013. All of the patients were systematically followed up to record the range of motion and other parameters before and after surgery. RESULTS: The mean preoperative flexion contracture was 17 degrees +/- 11 degrees (range, 0 degrees -40 degrees ), and it was 7 degrees +/- 12 degrees (range, 0 degrees -60 degrees ) postoperatively. The mean flexion of the knee was 73 degrees +/- 30 degrees (range, 5 degrees -135 degrees ) before the operation and 80 degrees +/- 19 degrees (range, 30 degrees -110 degrees ) at the last follow-up. The mean range of motion was 56 degrees +/- 34 degrees (range, 0 degrees -130 degrees ) before the operation and 73 degrees +/- 24 degrees (range, 10 degrees -110 degrees ) at the last follow-up. CONCLUSIONS: Statistical analysis suggested that the range of motion could be improved until the 9th postoperative week. The patient should be operated on until the flexion contracture reaches 22 degrees to obtain a contracture < 15 degrees postoperatively or until the contracture reaches 12 degrees to obtain less than 5 degrees . The operation generally does not change the flexion of the knee in cases of hemophilic patients, but it reduces the flexion contracture and therefore improves the range. PMID- 29788950 TI - Construct validity and reliability of the Finnish version of the Knee Injury and Osteoarthritis Outcome Score. AB - BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a commonly used knee assessment and outcome tool in both clinical work and research. However, it has not been formally translated and validated in Finnish. The purpose of this study was to translate and culturally adapt the KOOS questionnaire into Finnish and to determine its validity and reliability among Finnish middle-aged patients with knee injuries. METHODS: KOOS was translated and culturally adapted from English into Finnish. Subsequently, 59 patients with knee injuries completed the Finnish version of KOOS, Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short-Form 36 Health Survey (SF-36) and Numeric Pain Rating Scale (Pain-NRS). The same KOOS questionnaire was re-administered 2 weeks later. Psychometric assessment of the Finnish KOOS was performed by testing its construct validity and reliability by using internal consistency, test-retest reliability and measurement error. The floor and ceiling effects were also examined. RESULTS: The cross-cultural adaptation revealed only minor cultural differences and was well received by the patients. For construct validity, high to moderate Spearman's Correlation Coefficients were found between the KOOS subscales and the WOMAC, SF-36, and Pain-NRS subscales. The Cronbach's alpha was from 0.79 to 0.96 for all subscales indicating acceptable internal consistency. The test-retest reliability was good to excellent, with Intraclass Correlation Coefficients ranging from 0.73 to 0.86 for all KOOS subscales. The minimal detectable change ranged from 17 to 34 on an individual level and from 2 to 4 on a group level. No floor or ceiling effects were observed. CONCLUSION: This study yielded an appropriately translated and culturally adapted Finnish version of KOOS which demonstrated good validity and reliability. Our data indicate that the Finnish version of KOOS is suitable for assessment of the knee status of Finnish patients with different knee complaints. Further studies are needed to evaluate the predictive ability of KOOS in the Finnish population. PMID- 29788951 TI - Managing acute ischaemic stroke in a small island developing state: meeting the guidelines in Barbados. AB - BACKGROUND: We describe hospital-based management of acute ischaemic stroke patients in 2010-2013 in Barbados, by comparing documented treatment given in the single tertiary public hospital with international guideline recommendations. METHODS: Evidence-based stroke management guidelines were identified through a systematic literature search. Comparisons were made between these guidelines and documented diagnostic practice (all strokes) and prescribed medication (ischaemic stroke only), using a combination of key informant interviews and national stroke registry data for 2010-2013. RESULTS: Several published international guidelines for the acute management of ischaemic stroke recommended patient management in a dedicated stroke unit or nearest hospital specialised in stroke care. Further, patients should receive clinical diagnosis, CT brain scan, specialist evaluation by a multidisciplinary team and, if eligible, thrombolysis with alteplase within 3-3.5 h of symptom onset. Subsequent secondary prophylaxis, with a platelet aggregation inhibitor and a statin was advised. Barbados had no stroke unit or stroke team, and no official protocol for acute stroke management during the study period. Most of the 1735 stroke patients were managed by emergency physicians at presentation; if admitted, they were managed on general medical wards. Most had a CT scan (1646; 94.9%). Of 1406 registered ischaemic stroke patients, only 6 (0.4%) had been thrombolysed, 521 (37.1%) received aspirin within 24 h of admission and 670 (47.7%) were prescribed aspirin on discharge. CONCLUSIONS: Acute ischaemic stroke diagnosis was consistent with international recommendations, although this was less evident for treatment. While acknowledging the difficulty in implementing international guidelines in a low resource setting, there is scope for improvement in acute ischaemic stroke management and/or its documentation in Barbados. A stroke unit was established in August 2013 and written clinical protocols for acute stroke care were in development at the time of the study; future registry data will evaluate their impact. Our findings have implications for other low-resource settings with high stroke burden. PMID- 29788952 TI - Viruses in bronchiectasis: a pilot study to explore the presence of community acquired respiratory viruses in stable patients and during acute exacerbations. AB - BACKGROUND: Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. METHODS: This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. RESULTS: Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. CONCLUSIONS: This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently. PMID- 29788953 TI - "The missing ingredient": the patient perspective of health related quality of life in bronchiectasis: a qualitative study. AB - BACKGROUND: Bronchiectasis is a heterogeneous disease which affects quality of life. Measuring symptoms and quality of life has proved challenging and research is limited by extrapolation of questionnaires and treatments from other diseases. The objective of this study was to identify the major contributors to quality of life in bronchiectasis and to evaluate existing health related quality of life questionnaires in bronchiectasis. METHODS: Eight adults with bronchiectasis participated in one to one semi-structured interviews. These were recorded and transcribed verbatim. Thematic analysis was used to identify core themes relevant to disease burden and impact. Participant views on current health related quality of life questionnaires were also surveyed. RESULTS: Bronchiectasis symptoms are highly individual. Core themes identified were symptom burden, symptom variation, personal measurement, quality of life and control of symptoms. Themes contributing to quality of life were: social embarrassment, sleep disturbance, anxiety and modification of daily and future activities. Evaluation of 4 existing questionnaires established their individual strengths and weaknesses. A synthesis of the participants' perspective identified desirable characteristics to guide future tool development. CONCLUSIONS: This qualitative study has identified core themes associated with symptoms and quality of life in bronchiectasis. Current treatments and quality of life tools do not fully address or capture the burden of disease in bronchiectasis from the patients' perspective. PMID- 29788955 TI - Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM. METHODS: This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e' as a parameter of left ventricular diastolic function. RESULTS: A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 +/- 8.1 years (mean +/- SD), mean duration of diabetes was 13.5 +/- 8.1 years, and mean HbA1c was 7.9 +/- 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e' ratio 13.7 +/- 3.5-12.1 +/- 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e' ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e' ratio. CONCLUSIONS: This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values. Trial registration UMIN Clinical Trials Registry UMIN000028141. PMID- 29788956 TI - Building Bridges, Paediatric Palliative Care in Belgium: A secondary data analysis of annual paediatric liaison team reports from 2010 to 2014. AB - BACKGROUND: Although continuity of care in paediatric palliative care (PPC) is considered to be an essential element of quality of care, it's implementation is challenging. In Belgium, five paediatric liaison teams (PLTs) deliver palliative care. A Royal Decree issued in 2010 provides the legal framework that defines the PLTs' missions, as ensuring continuity of curative and palliative care between the hospital and home for children diagnosed with life-limiting conditions. This national study describes how PLTs ensure continuity of care by describing their activities and the characteristics of the children they cared for from 2010 to 2014. METHODS: Thematic analysis of open-ended questions was performed and descriptive statistics of aggregated data issued from annual reports, collected by the Belgian Ministry of Public Health through the Cancer Plan was used. A review panel of PLT members discussed the results and contributed to their interpretation. RESULTS: Between 2010 and 2014, 3607 children and young adults (0 21 years) were cared for by the 5 Belgian PLTs (mean of 721/per year). Of these children, 50% were diagnosed with an oncological disease, 27% with a neurological or metabolic disease. Four hundred and twenty eight (428) children had died. For 51% of them, death took place at home. PLT activities include coordination; communication; curative and palliative care; education; research and fundraising. Different perceptions of what constitutes a palliative stage, heterogeneity in reporting diagnosis and the current lack of specific valid indicators to report PPC activities were found. CONCLUSION: PLTs are offering highly individualised, flexible and integrated care from diagnosis to bereavement in all care settings. Improvements in data registration and implementation of outcome measures are foreseen. PMID- 29788954 TI - Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis. AB - Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations. PMID- 29788958 TI - Langerhans cell histiocytosis at L5 vertebra treated with en bloc vertebral resection: a case report. AB - BACKGROUND: Langerhans cell histiocytosis (LCH) in adult lumbar spine is extremely rare, and optimal treatments remain unclear. In literature, only a few cases of lumbar spine LCH were treated using surgery but en bloc vertebral resection has not been used. CASE PRESENTATION: A 50-year-old man presented with unbearable radiating pain at his right leg. Radiological studies revealed a solitary osteolytic lesion, which was moderately enhanced on contrast MR imaging and hyper-metabolic on PET/CT, at the right L5 vertebral body and arch. In biopsy, Langerhans cells were observed, but findings were insufficient to establish a diagnosis of LCH. A modified L5 en bloc vertebral resection via anterior and posterior approaches was performed to remove the right 2/3 portion of the L5 vertebra. The left 1/3 vertebral body and left pedicle of L5, which were not affected, were kept in situ to allow short instrumentation and reconstruction. His leg pain disappeared after the surgery, and a precise diagnosis of LCH was established after a throughout histological study of the removed vertebra. The patient further accepted 1 cycle of low-dose radiotherapy postoperatively. At 18-month follow-up, the lumbosacral spine was fused and no local reoccurrence was noticed. CONCLUSIONS: For lumbar spine LCH, surgery should be considered if there are neurological symptoms or histological diagnosis is indefinite in biopsy. En bloc vertebral resection can be used to alleviate neurological symptoms and prevent local reoccurrence. PMID- 29788957 TI - Endothelial progenitor cells improve the therapeutic effect of mesenchymal stem cell sheets on irradiated bone defect repair in a rat model. AB - BACKGROUND: The reconstruction of bone defects is often impaired by radiotherapy since bone quality is compromised by radiation. This study aims to investigate the therapeutic efficacy of the composite cell sheets-bone marrow mesenchymal stem cell (BMSC) sheets cocultured with endothelial progenitor cells (EPCs)-in the healing of irradiated bone defects and the biological effects of EPCs on the osteogenic properties of BMSC sheets. METHODS: BMSCs and EPCs were isolated from rat bone marrow. BMSCs were used to form cell sheets by the vitamin C inducing method. EPCs were seeded on BMSC sheets to make EPCs-BMSC sheets. Osteogenesis of EPCs-BMSC sheets and BMSC sheets were tested. In vitro osteogenesis tests included ALP, Alizarin Red S, Sirius Red staining, qRT-PCR and Western blot analysis after 3 and 7 days of osteogenic incubation. Subcutaneous osteogenesis was tested by H&E staining and immunohistochemical staining 8 weeks after transplantation. EPCs-BMSC sheets and BMSC sheets were used in the 3 mm defects of non-irradiated and irradiated rat tibias. Micro-CT and histological analysis were used to test the healing of bone defects 4 and 8 weeks after transplantation. RESULTS: EPCs-BMSC sheets showed enhanced osteogenic differentiation in vitro with increased expression of osteoblastic markers and osteogenesis related staining compared with BMSC sheets. In subcutaneous osteogenesis test, EPCs-BMSC sheets formed larger areas of new bone and blood vessels. The EPCs-BMSC group had the highest volume of newly formed bone in the defect area of irradiated tibias. CONCLUSIONS: EPCs improved the osteogenic differentiation of BMSC Sheets and enhanced the ectopic bone formation. EPCs-BMSC sheets promoted bone healing in irradiated rat tibias. EPCs-BMSC sheets are potentially useful in the reconstruction of bone defect after radiotherapy. PMID- 29788959 TI - Internal contracting of health services in Cambodia: drivers for change and lessons learned after a decade of external contracting. AB - BACKGROUND: Since the late 1990s, contracting has been employed in Cambodia in an attempt to accelerate rural health system recovery and improve health service delivery. Special Operating Agencies (SOA), a form of 'internal contracting', was introduced into selected districts by the Cambodia Ministry of Health in 2009. This study investigates how the SOA model was implemented and identifies effects on service delivery, challenges in operation and lessons learned. METHODS: The study was carried out in four districts, using mixed methods. Key informant interviews were conducted with representatives of donors and the Ministry of Health. In-depth interviews were carried out with managers of SOA and health facilities and health workers from referral hospitals and health centres. Data from the Annual Health Statistic Report 2009-2012 on utilisation of antenatal care, delivery and immunisation were analysed. RESULTS: There are several challenges with implementation: limited capacity and funding for monitoring the SOA, questionable reliability of the monitoring data, and some facilities face challenges in achieving the targets set in their contracts. There are some positive effects on staff behaviour which include improved punctuality, being on call for 24 h service, and perceived better quality of care, promoted through adherence to work regulations stipulated in the contracts and provision of incentives. However, flexibility in enforcing these regulations in SOA has led to more dual practice, compared to previous contracting schemes. There are reported increases in utilization of services by the general population and the poor although the quantitative findings question the extent to which these increases are attributable to the contracting model. CONCLUSION: Capacity in planning and monitoring contracts at different levels in the health system is required. Service delivery will be undermined if effective performance management is not established nor continuously applied. Improvements in the implementation of SOA include: better monitoring by the central and provincial levels; developing incentive schemes that tackle the issues of dual practice; and securing trustworthy baseline data for performance indicators. PMID- 29788960 TI - Ecto-5'-nucleotidase (CD73) attenuates inflammation after spinal cord injury by promoting macrophages/microglia M2 polarization in mice. AB - BACKGROUND: Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternatively activated M2 phenotype that confers anti-inflammatory effects. Ecto 5'-nucleotidase (CD73) is an immunosuppressive molecule intricately involved in adaptive and innate immune responses and is able to dephosphorylate AMP to adenosine. However, it is not known if CD73 is able to modulate the macrophages/microglia transformation between the M1 and M2 phenotypes. METHODS: We used gene-deficient mice to determine the role of CD73 in macrophages/microglia polarization post-SCI in vivo. We used small interference RNA (siRNA) or pcDNA3.1 to inhibit or overexpress CD73 in BV2 cells to verify anterior discovery in vitro. A combination of molecular and histological methods was used to detect the macrophages/microglia polarization and explore the mechanism both in vivo and in vitro. RESULTS: We found that SCI induced the upregulation of CD73 expression. CD73 deficient mice were noted to demonstrate overwhelming immune responses, few anti-inflammatory phenotype macrophages/microglia, and had a poorer locomotor recovery in comparison to wild type mice that were also inflicted with SCI. In vitro studies found that CD73 suppression inhibited the expression of characteristic microglial anti inflammatory polarization markers in BV2 cells, while the converse was noted in CD73 overexpression. Subsequent experiments confirmed that CD73 promoted microglia alternative activation by stimulating p38 MAPK. CONCLUSION: We were able to conclude that CD73 imparts neuroprotective effects by mediating macrophages/microglia polarization. These findings allow for better understanding of the modulatory factors involved in triggering the change in macrophages/microglia phenotypes, therefore uncovering additional molecules and pathways that may be targeted in the innovation of novel SCI therapies. PMID- 29788961 TI - Relationships among medication adherence, lifestyle modification, and health related quality of life in patients with acute myocardial infarction: a cross sectional study. AB - BACKGROUND: The healthy adherer effect is a phenomenon in which patients who adhere to medical therapies tend to pursue health-seeking behaviors. Although the healthy adherer effect is supposed to affect health outcomes in patients with coronary artery disease, evaluation of its presence and extent is not easy. This study aimed to assess the relationship between medication adherence and lifestyle modifications and health-related quality of life among post-acute myocardial infarction (AMI) patients. METHODS: A cross-sectional study was conducted in 417 post-AMI patients who underwent percutaneous coronary intervention (PCI). Patients were recruited from 11 university hospitals from December 2015 to March 2016 in South Korea. Details regarding socio-demographic factors, six health behaviors (low-salt intake, low-fat diet and/or weight-loss diet, regular exercise, stress reduction in daily life, drinking in moderation, and smoking cessation), medication adherence using the Modified Morisky Scale (MMS), and HRQoL using the Coronary Revascularization Outcome Questionnaire (CROQ) were surveyed in a one-on-one interview. RESULTS: In the univariate logistic analysis, sex (female), age (>=70 years), MMS score (>=5), and CROQ score were associated with adherence to lifestyle modification. In the multiple logistic analysis, a high MMS score (>=5) was associated with adherence to lifestyle modification after adjusting for sex, age, marital status, education, and family income (adjusted odds ratio [OR] = 11.7, 95% confidence interval [CI] = 1.5-91.3). After further adjusting for the CROQ score, the association between high MMS score and adherence to lifestyle modification was significant (adjusted OR = 11.5, 95% CI = 1.4-93.3). CONCLUSIONS: Adherence to medication was associated with adherence to lifestyle modification, suggesting the possible presence of the healthy adherer effect in post-AMI patients. After further adjusting for HRQoL, the association remained. To improve health outcome in post-AMI patients, early detection of patients with poor adherence to medication and lifestyle modification and motivational education programs to improve adherence are important. In addition, the healthy adherer effect should be considered in clinical research, in particular, in studies evaluating the effects of therapies on health outcomes. PMID- 29788963 TI - Cervical small cell carcinoma frequently presented in multiple high risk HPV infection and often associated with other type of epithelial tumors. AB - BACKGROUND: Small cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk HPV infections. METHODS: The clinicopathological data of 30 cases of cervical primary small cell carcinoma were retrospectively analyzed. In situ hybridization, polymerase chain reaction and reverse dot-blot hybridization were employed to detect HPV DNA in both small cell carcinoma and other coexisting epithelial tumors. Immunohistochemistry was used to detect the protein expression of p16 and p53. RESULTS: Amongst 30 patients with cervical primary small cell carcinoma, 15 patients simultaneously exhibited other types of epithelial tumors, including squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma in situ, and adenocarcinoma in situ. Most tumor cells infected with HPV presented integrated patterns in the nuclei by in situ hybridization. HPV DNA was detected in every small cell carcinoma case (100%) by polymerase chain reaction and reverse dot blot hybridization. 27 cases (90%) harbored type 18, and 15 (50%) displayed multiple HPV18 and 16 infections. The prevalence of HPV 18 infection in small cell carcinoma was higher than in cervical squamous and glandular epithelial neoplasms (P = 0.002). However, similar infection rates of HPV 16 were detected in both tumors (P = 0.383). Both small cell carcinoma and other types of epithelial tumors exhibited strong nuclear and cytoplasmic staining for p16 in all cases. Three cases of small cell carcinoma revealed completely negative p53 immunohistochemical expression in 15 cases of composite tumors, which suggested TP53 nonsense mutation pattern. The pure small cell carcinoma of uterine cervix had similar mutation or wild type pattern for TP53 compared with composite tumor (P = 0.224). CONCLUSIONS: Cervical small cell carcinomas are often associated with squamous or glandular epithelial tumors, which might result from multiple HPV infections, especially HPV 16 infection. Multiple HPV infections were not correlated with tumor stage, size, lymphovascular invasion, lymph node metastasis, or prognosis. Furthermore, careful observation of specimens is very important in finding little proportion of small cell carcinoma in the composite lesions, specifically in cervical biopsy specimens, in order to avoid the missed diagnosis of small cell carcinoma. PMID- 29788962 TI - Phenolics from Barleria cristata var. Alba as carcinogenesis blockers against menadione cytotoxicity through induction and protection of quinone reductase. AB - BACKGROUND: There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. METHODS: The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds. The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model. RESULTS: The ethyl acetate fraction of B. cristata var. alba yielded five known compounds identified as verbascoside (1), isoverbascoside (2), dimethoxyverbascoside (3), p-hydroxy benzoic acid (4), and apigenin-7-O-glucoside (5). Among the tested compounds, isoverbascoside (2) was shown to potently induce the activity of the enzyme in a dose -dependent manner. As a functional assay for detoxification, compound 2 was the strongest to protect Hepa-1c1c7 against the toxicity of menadione, a quinone substrate for NQO1. CONCLUSION: This effect seemed to be attributed to the compound's potential to induce both the catalytic activity and protein expression of NQO1 as revealed by enzyme assay and Western blotting, respectively. PMID- 29788964 TI - RNA sequencing analysis reveals quiescent microglia isolation methods from postnatal mouse brains and limitations of BV2 cells. AB - BACKGROUND: Microglia play key roles in neuron-glia interaction, neuroinflammation, neural repair, and neurotoxicity. Currently, various microglial in vitro models including primary microglia derived from distinct isolation methods and immortalized microglial cell lines are extensively used. However, the diversity of these existing models raises difficulty in parallel comparison across studies since microglia are sensitive to environmental changes, and thus, different models are likely to show widely varied responses to the same stimuli. To better understand the involvement of microglia in pathophysiological situations, it is critical to establish a reliable microglial model system. METHODS: With postnatal mouse brains, we isolated microglia using three general methods including shaking, mild trypsinization, and CD11b magnetic-associated cell sorting (MACS) and applied RNA sequencing to compare transcriptomes of the isolated cells. Additionally, we generated a genome-wide dataset by RNA sequencing of immortalized BV2 microglial cell line to compare with primary microglia. Furthermore, based on the outcomes of transcriptional analysis, we compared cellular functions between primary microglia and BV2 cells including immune responses to LPS by quantitative RT-PCR and Luminex Multiplex Assay, TGFbeta signaling probed by Western blot, and direct migration by chemotaxis assay. RESULTS: We found that although the yield and purity of microglia were comparable among the three isolation methods, mild trypsinization drove microglia in a relatively active state, evidenced by high amount of amoeboid microglia, enhanced expression of microglial activation genes, and suppression of microglial quiescent genes. In contrast, CD11b MACS was the most reliable and consistent method, and microglia isolated by this method maintained a relatively resting state. Transcriptional and functional analyses revealed that as compared to primary microglia, BV2 cells remain most of the immune functions such as responses to LPS but showed limited TGFbeta signaling and chemotaxis upon chemoattractant C5a. CONCLUSIONS: Collectively, we determined the optimal isolation methods for quiescent microglia and characterized the limitations of BV2 cells as an alternative of primary microglia. Considering transcriptional and functional differences, caution should be taken when extrapolating data from various microglial models. In addition, our RNA sequencing database serves as a valuable resource to provide novel insights for appropriate application of microglia as in vitro models. PMID- 29788965 TI - Diagnostic tools of caprine and ovine anaplasmosis: a direct comparative study. AB - BACKGROUND: The diagnosis of anaplasmosis is rather conflicting with other haemoprotozoans. Hence, the study aimed to compare and evaluate the efficiency of competitive ELISA (cELISA), indirect fluorescence antibody (IFA), and Polymerase chain reaction (PCR) for precise diagnosis of Anaplasma spp. and to assess their concordance with microscopic examination (ME). RESULTS: A total of 312 blood samples (189 sheep and 123 goats) were examined for Anaplasma infection during a 1 year period. Giemsa-stained blood smears were examined under the microscope. IFA and cELISA were used for the detection of Anaplasma spp. antibodies. PCR was used as a standard of truth and for the identification of Anaplasma species. Using cELISA assay, 47.4% (148) were positive (93 sheep and 55 goats) with a sensitivity and specificity of 91.9, and 86.9%, respectively. Using IFA, it was found that 57.4% (179)were positive (113 sheep and 66 goats) with a sensitivity and specificity of 100, and 93.3%, respectively. PCR assay identified A. ovis in 49 (25.3%) sheep and 30 (15.5%) goats, and A. phagocytophilumin 74 (38.1%) sheep and 41 (20.8%) goats. CONCLUSIONS: High sensitivity and specificity values of IFA and ELISA tests compared to microscopic examination strongly support their utility in the diagnosis of Anaplasma infection. PCR was a more specific diagnostic tool that allows to discriminate between Anaplasma subspecies, which makes it the method of choice for anaplasmosis diagnosis. PMID- 29788967 TI - Towards a culturally competent health professional: a South African case study. AB - BACKGROUND: South Africa (SA) has a growing multilingual and multicultural population of approximately 55 million people, and faces service delivery challenges due to a shortage in skilled health professionals. Many health care facilities still depict distinct racial and ethnic characteristics that date back to the apartheid era, and there are reports of racial intolerance or preferential treatment at some facilities. There is limited literature in South Africa on cultural competence or on how to train health professionals to provide culturally competent care. This paper describes a study conducted to gain a better understanding of final year medical students' perceptions regarding concepts related to cultural and linguistic competence in the SA healthcare setting. METHODS: An exploratory, cross-sectional, analytical study used a questionnaire to collect data from final year students at the medical school. RESULTS: The demographic profile indicated considerable diversity in the respondents for languages spoken, ethnicity and religion. Responses indicated a level of cultural awareness and, according to the Cross Framework, a position of cultural pre competence. This position was supported by the majority expressing high levels of agreement with the items deemed to indicate responsiveness: a desire for cultural competence to be promoted in the medical curriculum and for professional development to improve delivery of services and support to linguistically and culturally diverse groups. No significant association was found when analysing the latter item against demographic grouping variables. However, although not significant, a diminishing trend emerged in the rankings of monolingualism, bilingualism and multilingualism, suggesting that the ability to speak more than one language could possibly be a facilitating factor in acquiring cultural competence. CONCLUSIONS: In response, it is recommended that specific learning objectives be included in the medical curriculum. Understanding of concepts related to both individual and institutional cultural competence would improve insights into their relevance in responding to the challenges related to culture in SA healthcare. Further research in teaching cultural competence is recommended. In order to respond to local needs, this should include research at a community level to analyse patients' perspectives and satisfaction with the cultural competence of healthcare providers and organisations serving the SA public. PMID- 29788969 TI - Psychosocial predictors for outcome after total joint arthroplasty: a prospective comparison of hip and knee arthroplasty. AB - BACKGROUND: As findings regarding predictors for good outcome after total joint arthroplasty are highly inconsistent, aim of this study was to investigate the influence of the psychosocial variables sense of coherence and social support as well as mental distress on physical outcome after surgery. It should be investigated if different predictors are important in patients after total hip arthroplasty (THA) compared to patients after total knee arthroplasty (TKA). METHODS: In a prospective design, 44 patients undergoing THA and 61 patients undergoing TKA were examined presurgery and 6 and 12 weeks after surgery using WOMAC (disease-specific outcome), SF-36 (health-related quality of life), BSI (psychological distress), SOC-13 (sense of coherence), and F-SozU (social support). Changes over time were calculated by analyses of variance with repeated measures. Stepwise multiple linear regression analyses were computed for each group to predict scores of WOMAC total and all WOMAC subscales 12 weeks postoperatively. RESULTS: THA as well as TKA patients experienced improvements in all parameters (effect sizes for WOMAC scores between eta2 = .387 and eta2 = .631) with THA patients showing even better results than TKA patients. WOMAC scores 12 weeks after surgery were predicted predominantly by WOMAC baseline scores in TKA with an amount of explained variance between 9.6 and 19.5%. In THA, 12-weeks WOMAC scores were predicted by baseline measures of psychosocial aspects (anxiety, sense of coherence, social support). In this group, predictors accounted for 17.1 to 31.6% of the variance. CONCLUSIONS: Different predictors for outcome after total joint arthroplasty were obtained for THA and TKA patients. Although psychosocial aspects seemed to be less important in TKA patients, preoperatively, distressed patients of both groups should be offered interventions to reduce psychological distress to obtain better outcomes after surgery. PMID- 29788966 TI - Dyslipidemia prevalence, awareness, treatment, control, and risk factors in Chinese rural population: the Henan rural cohort study. AB - BACKGROUND: The prevalence of dyslipidemia continue to increase in recent decades in China, however, little is known about the recent prevalence, awareness, treatment, control, and potential risk factors of dyslipidemia in the rural areas of China. METHODS: A total of 39,207 participants aged 18-79 years were recruited for the epidemiological research from the Henan Rural Cohort study. The age- and sex-adjusted means (95% confidence intervals, CI) of serum lipid levels or percentages of prevalence, awareness, treatment, and control overall and in various population subgroups were estimated and compared by multiple linear regression or logistic regression. The multivariable logistic regression model was used to explore the associations between the socio-demographic factors and the prevalence, awareness, treatment and control of dyslipidemia. RESULTS: The age- and sex-adjusted mean levels (95%CI) of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.76(4.75-4.77), 1.68(1.67-1.69),1.33(1.32-1.33), and 2.87 (2.86-2.88) mmol/L, respectively. Overall, the age-standardized prevalence of dyslipidemia was 32.21% (42.85% in men vs. 26.16% in women) in Chinese rural adults, with 5.11, 16.00, 19.27, and 4.76% for high TC, high TG, low HDL-C and high LDL-C, respectively. The age-standardized awareness, treatment and control of dyslipidemia were 15.07, 7.23, and 3.25%, respectively, which were higher in women than men, and increased steeply with age (P trend < 0.05). The proportion of prevalence, awareness, treatment, control of dyslipidemia differed significantly among various subpopulations while the awareness, treatment, and control rates were universally low in all subgroups (< 54, 36, and 15%, respectively). Increasing age, men, unhealthy lifestyles, positive family history of dyslipidemia, abnormal weight, type 2 diabetes mellitus and hypertension were independent risk factors of dyslipidemia. CONCLUSION: Dyslipidemia was common with unacceptably low awareness, treatment and control rates in rural China. Therefore, effective strategies are necessary for improving the status of the prevention, diagnosis, treatment, control of dyslipidemia in Chinese rural residents. TRIAL REGISTRATION: ChiCTR-OOC-15006699. PMID- 29788968 TI - Spatio-temporal mapping of Madagascar's Malaria Indicator Survey results to assess Plasmodium falciparum endemicity trends between 2011 and 2016. AB - BACKGROUND: Reliable measures of disease burden over time are necessary to evaluate the impact of interventions and assess sub-national trends in the distribution of infection. Three Malaria Indicator Surveys (MISs) have been conducted in Madagascar since 2011. They provide a valuable resource to assess changes in burden that is complementary to the country's routine case reporting system. METHODS: A Bayesian geostatistical spatio-temporal model was developed in an integrated nested Laplace approximation framework to map the prevalence of Plasmodium falciparum malaria infection among children from 6 to 59 months in age across Madagascar for 2011, 2013 and 2016 based on the MIS datasets. The model was informed by a suite of environmental and socio-demographic covariates known to influence infection prevalence. Spatio-temporal trends were quantified across the country. RESULTS: Despite a relatively small decrease between 2013 and 2016, the prevalence of malaria infection has increased substantially in all areas of Madagascar since 2011. In 2011, almost half (42.3%) of the country's population lived in areas of very low malaria risk (<1% parasite prevalence), but by 2016, this had dropped to only 26.7% of the population. Meanwhile, the population in high transmission areas (prevalence >20%) increased from only 2.2% in 2011 to 9.2% in 2016. A comparison of the model-based estimates with the raw MIS results indicates there was an underestimation of the situation in 2016, since the raw figures likely associated with survey timings were delayed until after the peak transmission season. CONCLUSIONS: Malaria remains an important health problem in Madagascar. The monthly and annual prevalence maps developed here provide a way to evaluate the magnitude of change over time, taking into account variability in survey input data. These methods can contribute to monitoring sub-national trends of malaria prevalence in Madagascar as the country aims for geographically progressive elimination. PMID- 29788970 TI - An autopsy case of peripheral T cell lymphoma occurring in a postpartum woman: a unique case suggesting changes in the immunocharacteristics of lymphoma cells before and after delivery. AB - BACKGROUND: The occurrence of malignant lymphoma after delivery is an extremely rare event. Although several cases of Hodgkin lymphoma and B cell lymphoma and a few cases of peripheral T cell lymphoma (PTCL) after delivery have been reported, there are no report of autopsy cases of PTCL in the puerperal period. CASE PRESENTATION: A 32-year-old Japanese woman with a past medical history of atopic dermatitis and bronchial asthma presented with generalized eruptions four days after the delivery of her first child; generalized skin induration and lymphadenopathy subsequently emerged. A skin biopsy specimen showed the diffuse proliferation of atypical lymphoid cells that were immunohistochemically-positive for CD4 but negative for CD8. She was diagnosed as PTCL, not otherwise specified (PTCL, NOS). She died one year and three months after the onset of symptoms. At autopsy, the systemic infiltration of lymphoma cells into the whole body was observed. Unexpectedly, these lymphoma cells were immuno-reactive with CD8 but not with CD4. CONCLUSION: The occurrence and development of PTCL after delivery with the shift from CD4 positivity to CD8 positivity may be associated with not only the selection of resistant subclone as a result of chemotherapy but also the changes of immune status before and after delivery. PMID- 29788971 TI - Differential regulation of nimodipine-sensitive and -insensitive Ca2+ influx by the Na+/Ca2+ exchanger and mitochondria in the rat suprachiasmatic nucleus neurons. AB - BACKGROUND: Transmembrane Ca2+ influx is critical for molecular rhythmicity, metabolic activity, and neuropeptide release in the central clock of the suprachiasmatic nucleus (SCN). We previously reported that both the Na+/Ca2+ exchanger (NCX) and mitochondria play a role in regulating intracellular Ca2+ homeostasis in the rat SCN neurons. Here we present evidence to show differential regulation by NCX and mitochondria of nimodipine-sensitive and -insensitive Ca2+ influx. METHODS: Ratiometric Ca2+ imaging was used to measure change in [Ca2+]i and patch clamp recordings to study spontaneous firing, membrane potential, and voltage-dependent Ca2+ channels in neurons from reduced SCN slice preparations. Immunofluorescent staining was used to determine the distribution pattern of CaV1.2 and CaV1.3 and their colocalization with NCX1. RESULTS: Ratiometric Ca2+ imaging indicates that nimodipine (2 MUM) blocked most of 20 (mM) K+-induced, but less so of 50 K+-induced, Ca2+ rise. The nimodipine-sensitive 50 K+-induced Ca2+ transient rose more rapidly but decayed similarly with the nimodipine-insensitive component, suggesting both components were extruded by NCX. Immunofluorescent stains showed the expression of both CaV1.2 and CaV1.3 and their colocalization with NCX1, whereas functional studies suggest that CaV1.2 mediated most of the nimodipine-sensitive Ca2+ rise but had insignificant effect on spontaneous firing. After normalization relative to the Ca2+-free solution, nimodipine reduced ~ 65% of basal Ca2+ influx, and TTX lowered it by ~ 35%, leaving ~ 25% basal Ca2+ influx in the combined presence of TTX and nimodipine. With the mitochondrial uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) to inhibit mitochondrial Ca2+ uptake, 20 K+-induced Ca2+ transients became larger and slower, both in the absence and presence of nimodipine. FCCP markedly enhanced nimodipine-insensitive, but not nimodipine-sensitive, Ca2+ transients, suggesting that mitochondria preferentially buffer nimodipine-insensitive Ca2+ influx. Results from using CaV2 channel blockers further indicate that FCCP enhanced Ca2+ transients mediated by N-, P/Q-, and the blocker cocktail insensitive Ca2+ channels. CONCLUSIONS: The differential regulation of transmembrane Ca2+ influx by NCX and mitochondria suggests that Ca2+ entry via different sources may be regulated differently to play different roles in SCN physiology. PMID- 29788972 TI - Inequity in the utilization of antenatal and delivery care in Yangon region, Myanmar: a cross-sectional study. AB - BACKGROUND: Equity of access to and utilization of healthcare across socio economic groups is important to achieve universal health coverage. Although the utilization of antenatal and delivery care has been increasing in low- and middle income countries, inequities in the utilization of antenatal and delivery care have been reported in many countries, but have not yet been studied in Myanmar. This study aimed to determine whether inequities in the utilization of antenatal and delivery care existed in Yangon region, Myanmar. METHODS: A community-based cross-sectional survey using multistage sampling was conducted from October to November 2016. A wealth index was selected as the main socioeconomic parameter for measuring inequities with respect to early initiation of antenatal care (ANC), number of antenatal care visits, delivery by a skilled birth attendant (SBA) and delivery by cesarean section (CS). Inequities were evaluated using concentration curves and concentration indexes. RESULTS: Of the 762 women who gave birth within the 12-month survey period, there was no evidence of inequity in utilization of ANC; however, inequity of at least one antenatal visit among women aged less than 20 years was found with a concentration index of 0.04. The concentration indexes for delivery by SBA and CS were 0.05 and 0.14, respectively. Delivery by CS was disproportionately higher in adolescents and women with higher education than middle school. CONCLUSION: There was no overall inequity in the utilization of ANC but substantial inequities in delivery by CS and SBA were shown. Social determinants of health, particularly age and education, were associated with inequities in the utilization of delivery care. Adolescent pregnant women were found to be particularly vulnerable, and thus should be a target group for strategic plans to reduce inequities in utilization of delivery care. PMID- 29788973 TI - Homoharringtonine regulates the alternative splicing of Bcl-x and caspase 9 through a protein phosphatase 1-dependent mechanism. AB - BACKGROUND: Homoharringtonine (HHT) is a natural alkaloid with potent antitumor activity, but its precise mechanism of action is still poorly understood. METHODS: We examined the effect of HHT on alternative splicing of Bcl-x and Caspase 9 in various cells using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The mechanism of HHT-affected alternative splicing in these cells was investigated by treatment with protein phosphatase inhibitors and overexpression of a protein phosphatase. RESULTS: Treatment with HHT downregulated the levels of anti-apoptotic Bcl-xL and Caspase 9b mRNA with a concomitant increase in the mRNA levels of pro-apoptotic Bcl-xS and Caspase 9a in a dose- and time-dependent manner. Calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), significantly inhibited the effects of HHT on the alternative splicing of Bcl-x and Caspase 9, in contrast to okadaic acid, a specific inhibitor of PP2A. Overexpression of PP1 resulted in a decrease in the ratio of Bcl-xL/xS and an increase in the ratio of Caspase 9a/9b. Moreover, the effects of HHT on Bcl-x and Caspase 9 splicing were enhanced in response to PP1 overexpression. These results suggest that HHT induced alternative splicing of Bcl-x and Caspase 9 is dependent on PP1 activation. In addition, overexpression of PP1 could induce apoptosis and sensitize MCF7 cells to apoptosis induced by HHT. CONCLUSION: Homoharringtonine regulates the alternative splicing of Bcl-x and Caspase 9 through a PP1-dependent mechanism. Our study reveals a novel mechanism underlying the antitumor activities of HHT. PMID- 29788974 TI - Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice. AB - BACKGROUND: Eicosapentaenoic acid (EPA) is thought to have many beneficial effects, such as anti-atherosclerogenic and anti-inflammatory properties. However, few studies have reported its effects of endothelial dysfunction in diabetes and its direct effects on the aorta. Here, we investigated the effects of EPA treatment on impaired endothelium-dependent relaxation of the aorta in KKAy mice, a model of type 2 diabetes. METHODS: Male KKAy mice were fed a high fat (HF) diet for 8 weeks to induce diabetes, after which they were divided into two groups. One group was fed a HF diet, and the other group was fed a HF diet containing EPA ethyl ester (EPA-E, 10 mg/day) for 4 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if EPA-E administration changed vascular function in these diabetic mice. In addition, we examined effect of EPA-E and its metabolites to vascular action using aorta separated from C57BL/6 J mice. RESULTS: Although EPA-E administration did not change the plasma glucose and insulin levels in diabetic mice, total cholesterol levels were significantly decreased. The aorta extracted from EPA-E untreated diabetic mice showed impaired endothelium-dependent relaxation in response to acetylcholine (ACh). However, EPA-E administration improved the relaxation response to ACh to the control levels observed in non-diabetic C57BL/6 J mice. On the other hand, endothelium-independent relaxation in response to sodium nitroprusside did not significantly differ among these three groups. The enhanced contractile response by phenylephrine in diabetic mice was not altered by the administration of EPA-E. In addition, the direct administration of EPA-E metabolites such as EPA, docosahexaenoic acid, and docosapentaenoic acid led to vasodilation in the aortic rings of C57BL/6 J mice. CONCLUSION: These results showed that chronic EPA-E administration prevented the development of endothelial dysfunction in KKAy mice, partly via the direct action of EPA-E metabolites on the aorta. PMID- 29788976 TI - Improving the analysis of composite endpoints in rare disease trials. AB - BACKGROUND: Composite endpoints are recommended in rare diseases to increase power and/or to sufficiently capture complexity. Often, they are in the form of responder indices which contain a mixture of continuous and binary components. Analyses of these outcomes typically treat them as binary, thus only using the dichotomisations of continuous components. The augmented binary method offers a more efficient alternative and is therefore especially useful for rare diseases. Previous work has indicated the method may have poorer statistical properties when the sample size is small. Here we investigate small sample properties and implement small sample corrections. METHODS: We re-sample from a previous trial with sample sizes varying from 30 to 80. We apply the standard binary and augmented binary methods and determine the power, type I error rate, coverage and average confidence interval width for each of the estimators. We implement Firth's adjustment for the binary component models and a small sample variance correction for the generalized estimating equations, applying the small sample adjusted methods to each sub-sample as before for comparison. RESULTS: For the log-odds treatment effect the power of the augmented binary method is 20-55% compared to 12-20% for the standard binary method. Both methods have approximately nominal type I error rates. The difference in response probabilities exhibit similar power but both unadjusted methods demonstrate type I error rates of 6-8%. The small sample corrected methods have approximately nominal type I error rates. On both scales, the reduction in average confidence interval width when using the adjusted augmented binary method is 17-18%. This is equivalent to requiring a 32% smaller sample size to achieve the same statistical power. CONCLUSIONS: The augmented binary method with small sample corrections provides a substantial improvement for rare disease trials using composite endpoints. We recommend the use of the method for the primary analysis in relevant rare disease trials. We emphasise that the method should be used alongside other efforts in improving the quality of evidence generated from rare disease trials rather than replace them. PMID- 29788975 TI - Activism and scientific research: 20 years of community action by the Vancouver area network of drug users. AB - BACKGROUND: Over the past several decades, there have been numerous peer-reviewed articles written about people who use drugs (PWUDs) from the Downtown Eastside neighborhood of Vancouver, Canada. While individual researchers have engaged and acknowledged this population as participants and community partners in their work, there has been comparatively little attention given to the role of PWUDs and drug user organizations in directing, influencing, and shaping research agendas. METHODS: In this community-driven research, we examine 20 years of peer reviewed studies, university theses, books, and reports that have been directed, influenced, and shaped by members of the activist organization the Vancouver Area Network of Drug Users (VANDU). In this paper, we have summarized VANDU's work based on different themes from each article. RESULTS: After applying the inclusion criteria to over 400 articles, 59 items containing peer-reviewed studies, books, and reports were included and three themes of topics researched or discussed were identified. Theme 1: 'health needs' of marginalized groups was found in 39% of articles, Theme 2: 'evaluation of projects' related to harm reduction in 19%, and Theme 3: 'activism' related work in 42%. Ninety-four percent of co-authors were from British Columbia and 44% of research was qualitative. Works that have been co-authored by VANDU's members or acknowledged their participations created 628 citations. Moreover, their work has been accessed more than 149,600 times. CONCLUSIONS: Peer-based, democratic harm reduction organizations are important partners in facilitating groundbreaking health and social research, and through research can advocate for the improved health and wellbeing of PWUDs and other marginalized groups in their community. This article also recommends that PWUDs should be more respectfully engaged and given appropriate credit for their contributions. PMID- 29788977 TI - Exposure to a multi-level multi-component childhood obesity prevention community randomized controlled trial: patterns, determinants, and implications. AB - BACKGROUND: For community interventions to be effective in real-world conditions, participants need to have sufficient exposure to the intervention. It is unclear how the dose and intensity of the intervention differ among study participants in low-income areas. We aimed to understand patterns of exposure to different components of a multi-level multi-component obesity prevention program to inform our future impact analyses. METHODS: B'more Healthy Communities for Kids (BHCK) was a community-randomized controlled trial implemented in 28 low-income zones in Baltimore in two rounds (waves). Exposure to three different intervention components (corner store/carryout restaurants, social media/text messaging, and youth-led nutrition education) was assessed via post-intervention interviews with 385 low-income urban youths and their caregivers. Exposure scores were generated based on self-reported viewing of BHCK materials (posters, handouts, educational displays, and social media posts) and participating in activities, including taste tests during the intervention. For each intervention component, points were assigned for exposure to study materials and activities, then scaled (0-1 range), yielding an overall BHCK exposure score [youths: mean 1.1 (range 0-7.6 points); caregivers: 1.1 (0-6.7), possible highest score: 13]. Ordered logit regression analyses were used to investigate correlates of youths' and caregivers' exposure level (quartile of exposure). RESULTS: Mean intervention exposure scores were significantly higher for intervention than comparison youths (mean 1.6 vs 0.5, p < 0.001) and caregivers (mean 1.6 vs 0.6, p < 0.001). However, exposure scores were low in both groups and 10% of the comparison group was moderately exposed to the intervention. For each 1-year increase in age, there was a 33% lower odds of being highly exposed to the intervention (odds ratio 0.77, 95% confidence interval 0.69; 0.88) in the unadjusted and adjusted model controlling for youths' sex and household income. CONCLUSION: Treatment effects may be attenuated in community-based trials, as participants may be differentially exposed to intervention components and the comparison group may also be exposed. Exposure should be measured to provide context to impact evaluations in multi-level trials. Future analyses linking exposure scores to the outcome should control for potential confounders in the treatment-on-the-treated approach, while recognizing that confounding and selection bias may exist affecting causal inference. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02181010 . Retrospectively registered on 2 July 2014. PMID- 29788978 TI - Imaging diagnosis for chronic lateral ankle ligament injury: a systemic review with meta-analysis. AB - BACKGROUND: Various imaging techniques have been utilized for the diagnosis of chronic lateral ankle ligament injury. This systemic review will explore the effectiveness of different imaging techniques in diagnosing chronic lateral ankle ligament injury. METHODS: Relative studies were retrieved after searching 3 databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trails). Eligible studies were summarized. Data were extracted to calculate pooled sensitivity and specificity of magnetic resonance imaging (MRI), ultrasonography (US), stress radiography, and arthrography. RESULTS: Fifteen studies met our inclusion and exclusion criteria. A total of 695 participants were included. The pooled sensitivities in diagnosing chronic ATFL injury were 0.83 [0.78, 0.87] for MRI, 0.99 [0.96, 1.00] for US, and 0.81 [0.68, 0.90] for stress radiography. The pooled specificities in diagnosing chronic ATFL injury were 0.79 [0.69, 0.87] for MRI, 0.91 [0.82, 0.97] for US, and 0.92 [0.79, 0.98] for stress radiography. The pooled sensitivities in diagnosing chronic CFL injury were 0.56 [0.46, 0.66] for MRI, 0.94 [0.85, 0.98] for US, and 0.90 [0.73, 0.98] for arthrography. The pooled specificities in diagnosing chronic CFL injury were 0.88 [0.82, 0.93] for MRI, 0.91 [0.80, 0.97] for US, and 0.90 [0.77, 0.97] for arthrography. CONCLUSION: This systematic review with meta-analysis investigated the accuracy of imaging for the diagnosis of chronic lateral ankle ligament injury. Ultrasound manifested high diagnostic accuracy in diagnosing chronic lateral ankle ligament injury. Clinicians should be aware of the limitations of MRI in detecting chronic CFL injuries. PMID- 29788980 TI - Treatment of ventriculoperitoneal shunt infection and ventriculitis caused by Acinetobacter baumannii: a case report. AB - BACKGROUND: Acinetobacter baumannii (A. baumannii) infections are a recognized problem in healthcare, causing ventriculoperitoneal shunt infection and ventriculitis. Such infections are serious intracranial infection that can lead to serious complication and death. Treatment of infection caused by A. baumannii becomes difficult because of its inclination to develop pandrug resistance to the universally used antibiotics. In this case, we focused on pediatric ventriculitis/shunt infection caused by A. baumannii in an extensive follow-up and report the subsequent treatment outcome. Very limited information regarding the therapeutic options against A. baumannii ventriculitis/shunt infection is available in our hospital. Thus, we present one such case and the problems in its treatment. CASE PRESENTATION: We reported the case of a 6-year-old Ethiopian boy who developed ventriculitis/shunt infection from the pandrug-resistant strain of A. baumannii, after decompression of a craniotomy for medulloblastoma. Following the surgical procedure, he had developed hydrocephalus and ventriculoperitoneal shunt infection/ventriculitis as he presented with persistent fever, elevated white blood cell count, reduced glucose level, and the cerebrospinal fluid culture revealed A. baumannii, which was not responding to most of commercially available antibiotics systemically. Our patient was successfully treated with intravenous ampicillin-sulbactam. CONCLUSIONS: We presented our case of pandrug resistant A. baumannii ventriculoperitoneal shunt infection and ventriculitis successfully treated with a systemic ampicillin-sulbactam. Provision of systemic ampicillin-sulbactam should not be undermined. Therefore, this case exemplifies that intravenous administration of ampicillin-sulbactam can be a good therapeutic option against A. baumannii ventriculoperitoneal shunt infection and ventriculitis. PMID- 29788981 TI - Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial. AB - BACKGROUND: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non Asian subpopulations. METHODS: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). RESULTS: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%). CONCLUSIONS: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00720941 , Registered July 22, 2008 ClinicalTrials.gov, NCT01147822 , Registered June 22, 2010. PMID- 29788982 TI - TISU: Extracorporeal shockwave lithotripsy, as first treatment option, compared with direct progression to ureteroscopic treatment, for ureteric stones: study protocol for a randomised controlled trial. AB - BACKGROUND: Urinary stone disease is very common with an estimated prevalence among the general population of 2-3%. Ureteric stones are associated with severe pain as they pass through the urinary tract and have significant impact on patients' quality of life due to the detrimental effect on their ability to work and need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care. However, between one-fifth and one-third of cases require an intervention. The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. ESWL and ureteroscopy are effective in terms of stone clearance; however, they differ in terms of invasiveness, anaesthetic requirement, treatment setting, complications, patient-reported outcomes (e.g. pain after intervention, time off work) and cost. There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the NHS and to society (in terms of impact on patient-reported health and economic burden). The aim of this trial is to determine whether, in adults with ureteric stones, judged to require active intervention, ESWL is not inferior and is more cost-effective compared to ureteroscopic treatment as the initial management option. METHODS: The TISU study is a pragmatic multicentre non-inferiority randomised controlled trial of ESWL as the first treatment option compared with direct progression to ureteroscopic treatment for ureteric stones. Patients aged over 16 years with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) will be randomised to either ESWL or ureteroscopy. The primary clinical outcome is resolution of the stone episode (no further intervention required to facilitate stone clearance) up to six months from randomisation. The primary economic outcome is the incremental cost per quality adjusted life years (QALYs) gained at six months from randomisation. DISCUSSION: Determining whether ESWL is not inferior clinically and is cost-effective compared to ureteroscopic treatment as the initial management in adults with ureteric stones who are judged to require active treatment is relevant not only to patients and clinicians but also to healthcare providers, both in the UK and globally. TRIAL REGISTRATION: ISRCTN registry, ISRCTN92289221 . Registered on 21 February 2013. PMID- 29788983 TI - Role of pulmonary hemodynamics in determining 6-minute walk test result in atrial septal defect: an observational study. AB - BACKGROUND: The presence of altered pulmonary hemodynamics in adult patients with atrial septal defect (ASD) is common. However, there are no observational studies which evaluate the impact of altered pulmonary hemodynamics on the 6-min walk test (6MWT) result. This study aimed to investigate the role of pulmonary hemodynamics in determining 6MWT result of patients with ASD. METHOD: Forty-six consecutive adult patients with ASD were included in this study. Right heart catheterization was performed to obtain the pulmonary hemodynamics profile. Meanwhile, 6MWT was presented as high or low with cut-off point 350 m. Receiver operating characteristic (ROC) was used for analytical methods. RESULT: Abnormal functional capacity was indicated by ROC result of mPAP cut-off value of > 24 mmHg (p = 0.0243; AUC = 0.681). The value of PVR > 3.42 woods unit (WU) showed high specificity in determining abnormal functional capacity (p = 0.0069; AUC = 0.713). Flow ratio with cut-off point <=4.89 had the highest sensitivity (100%) (p = 0.8300; AUC = 0.520). CONCLUSION: Pulmonary hemodynamics can serve as an indicator of 6MWT result in adult ASD patients with values of mPAP> 24 mmHg and PVR > 3.42 WU. PMID- 29788979 TI - MARCKS and MARCKS-like proteins in development and regeneration. AB - BACKGROUND: The Myristoylated Alanine-Rich C-kinase Substrate (MARCKS) and MARCKS like protein 1 (MARCKSL1) have a wide range of functions, ranging from roles in embryonic development to adult brain plasticity and the inflammatory response. Recently, both proteins have also been identified as important players in regeneration. Upon phosphorylation by protein kinase C (PKC) or calcium-dependent calmodulin-binding, MARCKS and MARCKSL1 translocate from the membrane into the cytosol, modulating cytoskeletal actin dynamics and vesicular trafficking and activating various signal transduction pathways. As a consequence, the two proteins are involved in the regulation of cell migration, secretion, proliferation and differentiation in many different tissues. MAIN BODY: Throughout vertebrate development, MARCKS and MARCKSL1 are widely expressed in tissues derived from all germ layers, with particularly strong expression in the nervous system. They have been implicated in the regulation of gastrulation, myogenesis, brain development, and other developmental processes. Mice carrying loss of function mutations in either Marcks or Marcksl1 genes die shortly after birth due to multiple deficiencies including detrimental neural tube closure defects. In adult vertebrates, MARCKS and MARCKL1 continue to be important for multiple regenerative processes including peripheral nerve, appendage, and tail regeneration, making them promising targets for regenerative medicine. CONCLUSION: This review briefly summarizes the molecular interactions and cellular functions of MARCKS and MARCKSL1 proteins and outlines their vital roles in development and regeneration. PMID- 29788984 TI - F-18 FDG PET/CT in 26 patients with SAPHO syndrome: a new vision of clinical and bone scintigraphy correlation. AB - BACKGROUNDS: Whole-body bone scintigraphy (WBBS) and MRI are widely used in assessment of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. However, the value of F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) in SAPHO syndrome was unclear. The aim of this study was to characterize the manifestation of SAPHO syndrome on 18F-FDG PET/CT and explore its relationship with clinical symptoms and WBBS. METHODS: Twenty-six patients who suffered from SAPHO syndrome and had undergone whole-body 18F-FDG PET/CT were recruited in Peking Union Medical College Hospital from 2004 to 2016. Clinical manifestations and laboratory findings were recorded for all patients. Imaging data on 18F-FDG PET/CT and WBBS were collected and analyzed retrospectively. RESULTS: All the 26 patients (20 females and 6 males) exhibited skeletal abnormalities on 18F-FDG PET/CT. Multiple skeletal lesions affecting the anterior chest wall or spine with low to moderate 18F-FDG uptake and coexistence of osteolysis and osteosclerosis presented as the typical features of SAPHO syndrome. Sixteen (61.5%) patients had abnormal 18F-FDG uptake outside the osteoarticular system. PET scan had moderate to substantial agreement with CT and WBBS in revealing lesions in the anterior chest wall and axial skeleton. Nonetheless, the correlation between increased 18F-FDG uptake and clinical symptoms was weak. CONCLUSIONS: SAPHO syndrome exhibits characteristic features on 18F-FDG PET/CT. It showed comparable capacity in revealing skeletal lesions with bone scintigraphy. PMID- 29788986 TI - Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients. AB - BACKGROUND: Pompe disease is a rare metabolic myopathy. In adult patients, progressive weakness of limb-girdle and respiratory muscles often leads to wheelchair and respirator dependency. Clinical studies have shown enzyme replacement therapy (ERT) to positively affect motor and respiratory outcomes. Here we investigate whether ERT reduces patients' risk of needing a wheelchair or respirator. METHODS: Data were collected as part of a prospective international survey, the IPA/Erasmus MC Pompe survey, which was conducted annually between 2002 and 2016. We excluded patients who were already using a wheelchair or respirator, those under 18 at survey entry, and those who had missing information. Time-dependent Cox proportional hazard models were used. RESULTS: The inclusion criteria for analyzing the risk of wheelchair use were met by 189 patients (median age 47 years; range 18-75). During follow-up, 126 (67%) started ERT. Over 1120 person-years of follow-up (median 5 years), 46 became wheelchair dependent, 16 of whom used ERT. After adjustment for disease duration, sex and country, ERT reduced the risk for wheelchair use (HR 0.36; 95% CI 0.17-0.75). For analyses of respirator use, 177 patients met the inclusion criteria (median age 46 years; range 18-73). Over 1190 person-years of follow-up (median 6 years), 125 patients (71%) were treated and 48 started respiratory support, 28 of whom received ERT. We found no association between ERT and the risk for respirator use (HR 1.23; 95% CI 0.61-2.47). CONCLUSIONS: Our study found that ERT reduced the risk for wheelchair dependency. We could not demonstrate an effect on respiratory support. PMID- 29788985 TI - Establishment of lung cancer patient-derived xenograft models and primary cell lines for lung cancer study. AB - BACKGROUND: The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. METHODS: 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines. Tumor growth measurements, histological and immunohistochemistry analysis, Western blotting, EGFR and K-RAS mutation detection and gefitinib sensitive assay were performed to evaluate the characteristic of established PDX models. Immunofluorescence analysis, anchorage independent cell growth, Western blotting and gefitinib sensitive assay were performed to assay the characteristic of established primary cell lines. The whole-exome sequencing was used to compare the characteristic of the patient's tumor tissue, established PDX and primary cell line. RESULTS: Twenty-one lung cancer PDX models (67.74%, 21/31) and ten primary cell lines (32.25%, 10/31) were established from patients' tumor tissues. The histology and pathological immunohistochemistry of PDX xenografts are consistent with the patients' tumor samples. Various signal pathways were activated in different PDX models (n = 5) and primary cell lines (n = 2). EGFR mutation PDX model and primary cell line (LG1) were sensitive to gefitinib treatment. The expression of CK8/18, TTF1 and NapsinA in LG1 and LG50 primary cells were also positive. And the activated signal pathways were activated in LG1 and LG50 primary cell lines. Furthermore, the gene mutation in PDX tumor tissues and primary cell line (LG50) was consistent with the mutation in LG50 patient's tumor tissues. CONCLUSION: These data suggested that established lung cancer PDX models and primary cell lines reserved mostly molecular characteristics of primary lung cancer and could provide a new tool to further understand the mechanisms and explore new therapeutic strategies. PMID- 29788987 TI - Efficacy of the Buzzy(r) device for pain management of children during needle related procedures: a systematic review protocol. AB - BACKGROUND: Needle-related procedures are the most important source of pain in children in hospital setting. Unmanaged pain could result in short- and long-term physiological, psychological, and emotional consequences. Although the efficacy of numerous interventions has been evaluated, procedural pain management is often suboptimal in children undergoing needle-related procedures. The main objective of this systematic review is to examine the evidence for the efficacy of the Buzzy(r) device for needle-related procedural pain in children. METHODS: An electronic search will be conducted in the following databases: CENTRAL, PubMed, MEDLINE, EMBASE, PsycInfo, and CINAHL. There will be no restriction regarding the language, date of publication, and publication status. Eligible studies will be randomized controlled trials using the Buzzy(r) device for pain management in children undergoing needle-related procedures. Selection of studies, data extraction and management, assessment of risk of bias and quality of evidence will be performed by two independent reviewers. A third researcher will be consulted in case of discrepancies. Depending on the availability and quality of the data as well as clinical and statistical heterogeneity, a meta-analysis will be performed. Otherwise, findings will be qualitatively reported. DISCUSSION: This will be the first systematic review to examine the efficacy of the Buzzy(r) device on pain management of children during needle-related procedures. Results of this review will guide clinical practice and recommendations for further research to improve procedural pediatric pain management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017076531. PMID- 29788988 TI - Prevalence and antimicrobial susceptibility patterns of extended spectrum beta lactamase producing Entrobacteriaceae in the University of Gondar Referral Hospital environments, northwest Ethiopia. AB - OBJECTIVE: This study aimed at assessing the magnitude, distribution, and the antimicrobial susceptibility of the extended spectrum beta-lactamase producing Entrobacteriaceae in the University of Gondar Referral Hospital environments. RESULTS: Out of a total of 384 samples, 14.8% were ESBL producing Entrobacteriaceae, where 42.10% Klebsiella pneumoniae, 35.09% Escherchia coli and 7.01% Proteus mirabilis were the predominant isolates. Most ESBL producing isolates, that is, 24.56, 22.8, and 22.8% were found from waste water, sinks and bedside tables respectively. All ESBL producing Entrobacteriaceae were found to be resistant to ceftriaxone, ceftazidime, cefpirome, cefpodoxime, and amoxicillin with Clavulanic acid. Resistance rate was also high for non-beta-lactam antimicrobials, like chloramphenicol (70.18%), cotrimoxazole (64.91%), norfloxacin (42.10%), ciprofloxacin (43.86%), and gentamicin (19.30%). PMID- 29788989 TI - Loop ostomy following laparoscopic low anterior resection for rectal cancer after neoadjuvant chemoradiotherapy. AB - BACKGROUND: Both loop ileostomy (LI) and loop transverse colostomy (LTC) could achieve absolute fecal diversion and have several advantages. This study compared LI and LTC following laparoscopic low anterior resection for rectal cancer after neoadjuvant chemoradiotherapy. METHODS: Between January 2009 and December 2016, 186 patients who underwent laparoscopic low anterior resection for rectal cancer and loop ostomy were included. All patients received preoperative neoadjuvant chemoradiotherapy. Of these, 77 underwent LI and 109 underwent LTC. Demographic characteristics, operative details, and complications were analyzed. RESULTS: In the fecal diversion period, the LTC group showed significantly less dermatitis (p = 0.001) and electrolyte disturbance (p = 0.002), while LI group showed significantly shorter time to first defecation (p = 0.006) and lower incidence of parastomal hernia (p = 0.014). In the stoma closure period, a significantly higher incidence of wound infection was found in LTC group (p = 0.001). CONCLUSIONS: Both LI and LTC have advantages and disadvantages. For its lower wound infection rate, lower incidence of parastomal hernia, and shorter time to first defecation, LI is recommended for all patients except those with potential electrolyte disturbance and sensitive skin. PMID- 29788990 TI - Impact of anticoagulation and vasoactive medication on regained radial artery patency after catheterization: a case-control study. AB - BACKGROUND: Radial artery access is the primary approach for coronary interventions due to higher safety profile in comparison to femoral access. Radial artery occlusion (RAO) is the main complication of transradial catheterization that can lead to severe symptoms and a permanent artery occlusion. The incidence of RAO after transradial access ranges from 5 to 38% and data regarding treatment is scarce. Whether anticoagulation and vasoactive medication provides an additional benefit in recovery of radial artery patency (RAP) after catheterization has not been investigated in detail. AIM: The objective was to investigate the impact of anticoagulation and vasoactive medication on regained patency after documented RAO following transradial catheterization. PATIENTS AND METHODS: Overall 2635 patients were screened. 2215 (84%) catheterizations were performed by femoral and 420 (16%) by radial access. In 30 patients RAO was observed. In case of RAO patients were classified in three groups: Anticoagulation, anticoagulation added with alprostadil and controls. Follow-up was conducted after 3 months with ultrasound and clinical examination. RESULTS: Eight patients received anticoagulation and 11 patients anticoagulation together with alprostadil. Eleven patients served as controls. Recovery of RAP after catheterization was higher following either treatment (79.5%) compared to controls (0%, p = 0.006). Subgroup analysis yielded a higher RAP recovery in patients treated with anticoagulation (62.5%) as compared to controls (0%, p = 0.002). No effect on regained RAP was found with additional alprostadil therapy (33.3%) compared to anticoagulation therapy (62.5%, p = 0.229). CONCLUSION: RAO should be treated with anticoagulation to regain patency. Addition of vasoactive medication does not lead to further beneficial effects. Further research is needed regarding preventive and therapeutic strategies following RAO. PMID- 29788991 TI - Bilateral tympanokeratomas (cholesteatomas) with bilateral otitis media, unilateral otitis interna and acoustic neuritis in a dog. AB - BACKGROUND: An aural cholesteatoma, more appropriately named tympanokeratoma, is an epidermoid cyst of the middle ear described in several species, including dogs, humans and Mongolian gerbils. The cyst lining consists of stratified, keratinizing squamous epithelium with central accumulation of a keratin debris. This case report describes vestibular ganglioneuritis and perineuritis in a dog with chronic otitis, bilateral tympanokeratomas and presumed extension of otic infection to the central nervous system. CASE PRESENTATION: An 11-year-old intact male Dalmatian dog with chronic bilateral otitis externa and sudden development of symptoms of vestibular disease was examined. Due to the dog's old age the owner opted for euthanasia without any further examination or treatment and the dog was submitted for necropsy. Transection of the ears revealed grey soft material in the external ear canals and pearly white, dry material consistent with keratin in the tympanic bullae bilaterally. The brain and meninges were grossly unremarkable. Microscopical findings included bilateral otitis externa and media, unilateral otitis interna, ganglioneuritis and perineuritis of the spiral ganglion of the vestibulocochlear nerve and multifocal to coalescing, purulent meningitis. A keratinizing squamous epithelial layer continuous with the external acoustic meatus lined the middle ear compartments, consistent with bilateral tympanokeratomas. Focal bony erosion of the petrous portion of the temporal bone and squamous epithelium and Gram-positive bacterial cocci were evident in the left cochlea. The findings suggest that meningitis developed secondary to erosion of the temporal bone and ganglioneuritis and/or perineuritis of the vestibulocochlear nerve. CONCLUSIONS: Middle ear tympanokeratoma is an important and potentially life-threatening otic condition in the dog. Once a tympanokeratoma has developed expansion of the cyst can lead to erosion of bone and extension of otic infection to the inner ear, vestibulocochlear ganglion and nerve potentially leading to bacterial infection of the central nervous system. PMID- 29788992 TI - Comparing case-control study for treatment of proximal tibia fractures with a complete metaphyseal component in two centers with different distinct strategies: fixation with Ilizarov frame or locking plates. AB - BACKGROUND: The purpose of this study was to compare two methods of stabilization for proximal tibia fractures (AO 41) with a complete metaphyseal component, external fixation with the Ilizarov wire frame, and internal fixation with locking plates. METHODS: Patients from two level 1 trauma centers treated between 2009 and 2015 were included in a retrospective comparing cohort study. The first center stabilized the non-pathological, proximal tibia fractures exclusively with external fixation and the second with internal plating. Combined clinically and radiologically evaluated, bone healing was the primary outcome. The secondary outcomes included complications, range of motion (ROM) and axial alignment of the knee, the reoperation rate within 6 months, heterotopic ossifications (HTO), and signs of posttraumatic osteoarthritis (PTOA). A logistic regression analysis corrected for uneven distributed parameters. RESULTS: The 62 patients treated with Ilizarov frame and the 68 patients treated with plate fixation were comparable regarding epidemiological parameters, injury characteristics, and comorbidity except for injury severity score (ISS) and smoking behavior. The time of healing was shorter in the group undergoing plate fixation (p = 0.041); however, the incidence of non-unions was equal. Furthermore, there was no difference regarding the rate of deep infections, thrombosis, alignment, reoperations, PTOA, and ROM. Heterotopic ossifications were more prevalent following plate fixation (13.2 vs 1.6%, p = .013). External fixation was associated with a higher rate of superficial infections (40.4 vs 2.9%, p = .000). The initial displacement, the incidence of deep infections, and the classification significantly influenced the incidence of non-unions in both groups (p < 0.02). CONCLUSIONS: Fixation of proximal tibia fractures with plates resulted in a slightly shorter healing time compared to Ilizarov frame stabilization. Furthermore, the complication profiles differ with more heterotopic ossifications and less superficial infections following internal plating. TRIAL REGISTRATION: DRKS, DRKS00013275 , Registered 11/2/2017, Retrospectively registered. PMID- 29788993 TI - Acetylcholine receptor antagonists in acute respiratory distress syndrome: much more than muscle relaxants. AB - Acetylcholine receptor antagonists have been shown to improve outcome in patients with severe acute respiratory distress syndrome. However, it is incompletely understood how these agents improve outcome. In the current editorial, we discuss the mechanisms of action of acetylcholine receptor antagonists beyond neuromuscular blockade. PMID- 29788994 TI - Tick abundance, pathogen prevalence, and disease incidence in two contrasting regions at the northern distribution range of Europe. AB - BACKGROUND: Emergence of tick-borne diseases is impacting humans and livestock across the Northern Hemisphere. There are, however, large regional variations in number of cases of tick-borne diseases. Some areas have surprisingly few cases of disease compared to other regions. The aim here is to provide a first step towards a better understanding of such contrasting regional patterns of disease emergences at the northern distribution range of Ixodes ricinus in Europe. METHODS: We compare disease incidence, vector abundance and pathogen prevalence in eastern and western Norway differing in the number of tick-borne disease cases. First, we analysed the incidence of Lyme borreliosis in humans, tick-borne fever (anaplasmosis) in sheep and anaplasmosis and babesiosis in cattle to verify if incidence differed. Secondly, we analysed extensive field data on questing tick density, pathogen prevalence, as well as the broad spatial pattern of human and livestock distribution as it may relate to tick exposure. RESULTS: The incidences of all diseases were lower in eastern, compared to western, Norway, but this was most marked for the livestock diseases. While the prevalence of Borrelia burgdorferi (sensu lato) in ticks was similar in the two regions, the prevalence of Anaplasma phagocytophilum was markedly lower in eastern, compared to western, Norway. We found overall a lower abundance of questing nymphs in the east. In the east, there were cases of babesiosis in cattle where anaplasmosis was absent, suggesting absence of the pathogen rather than differences in exposure to ticks as part of the explanation for the much lower incidence of anaplasmosis in eastern Norway. CONCLUSIONS: Many factors contribute to different disease incidence across ecosystems. We found that regional variation in tick borne disease incidence may be partly linked to vector abundance and pathogen prevalence, but differently for human and livestock diseases. Further studies are needed to determine if there is also regional variation in specific genospecies and strain frequencies differing in pathogenicity. PMID- 29788995 TI - In vitro chemokine (C-C motif) receptor 6-dependent non-inflammatory chemotaxis during spermatogenesis. AB - BACKGROUND: Chemokine (C-C motif) receptor 6 (CCR6) is present in sperm and plays a significant role in sperm motility and chemotaxis acting in the reproductive tracts. However, the expression and functional significance of CCR6 in testis are still poorly understood, especially in the process of spermatogenesis. METHODS AND RESULTS: CCR6 was expressed in spermatogenic cell lines and its expression was shown in an age-dependent upregulation manner from puberty to adulthood in mouse testis. Immunostaining results confirmed the localization of CCR 6 in testis. Further chemotaxis assays demonstrated that spermatogenic cells GC-1 and 2 exhibited a directional movement toward CCR6-specific ligand such as CCL20 or Sertoli cells in vitro. CONCLUSIONS: The present findings indicate that CCR6 is involved in the chemotaxis of spermatogenic cells in vitro and promotes chemotaxis under non-inflammatory conditions during normal spermatogenesis. PMID- 29788996 TI - Effectiveness and acceptance of a web-based depression intervention during waiting time for outpatient psychotherapy: study protocol for a randomized controlled trial. AB - BACKGROUND: Due to limited resources, waiting periods for psychotherapy are often long and burdening for those in need of treatment and the health care system. In order to bridge the gap between initial contact and the beginning of psychotherapy, web-based interventions can be applied. The implementation of a web-based depression intervention during waiting periods has the potential to reduce depressive symptoms and enhance well-being in depressive individuals waiting for psychotherapy. METHODS: In a two-arm randomized controlled trial, effectiveness and acceptance of a guided web-based intervention for depressive individuals on a waitlist for psychotherapy are evaluated. Participants are recruited in several German outpatient clinics. All those contacting the outpatient clinics with the wish to enter psychotherapy receive study information and a depression screening. Those adults (age >= 18) with depressive symptoms above cut-off (CES-D scale > 22) and internet access are randomized to either intervention condition (treatment as usual and immediate access to the web-based intervention) or waiting control condition (treatment as usual and delayed access to the web-based intervention). At three points of assessment (baseline, post treatment, 3-months-follow-up) depressive symptoms and secondary outcomes, such as quality of life, attitudes towards psychotherapy and web-based interventions and adverse events are assessed. Additionally, participants' acceptance of the web-based intervention is evaluated, using measures of intervention adherence and satisfaction. DISCUSSION: This study investigates a relevant setting for the implementation of web-based interventions, potentially improving the provision of psychological health care. The results of this study contribute to the evaluation of innovative and resource-preserving health care models for outpatient psychological treatment. TRIAL REGISTRATION: This trial has been registered on 13 February 2017 in the German clinical trials register (DRKS); registration number DRKS00010282 . PMID- 29788998 TI - Depression screening and education: an examination of mental health literacy and stigma in a sample of Hispanic women. AB - BACKGROUND: Mental health literacy consists of knowledge of a mental disorder and of the associated stigma. Barriers to depression treatment among Hispanic populations include persistent stigma which is primarily perpetuated by inadequate disease literacy and cultural factors. U.S.-born Hispanics are more likely to have depression compared to Hispanics born in Latin America and are less likely to follow a treatment plan compared to non-Hispanic whites. Hispanic women are more likely to access treatment through a primary care provider, making it an ideal setting for early mental health interventions. METHODS: Baseline data from 319 female Hispanic patients enrolled in Project DESEO: Depression Screening and Education: Options to Reduce Barriers to Treatment, were examined. The study implemented universal screening with a self-report depression screening tool (the 9-item Patient Health Questionnaire (PHQ-9) and took place at one federally qualified health center (FQHC) over a 24-month period. The current analysis examined the relationship between four culturally adapted stigma measures and depression knowledge, and tested whether mental health literacy was comparable across education levels in a sample of Hispanic women diagnosed with depression. RESULTS: Almost two-thirds of the sample had less than a high school education. Depression knowledge scores were significantly, weakly correlated with each the Stigma Concerns About Mental Health Care (rho = - .165, p = .003), Latino Scale for Antidepressant Stigma (p = .124, p = .028), and Social Distance scores (p = .150, p = .007). Depression knowledge (F[2, 312] = 11.82, p < .001, partial eta2 = .071), Social Distance scores (F[2, 312] = 3.34, p = .037, partial eta2 = .021), and antidepressant medication stigma scores (F[2, 312] = 3.33, p = .037, partial eta2 = .015) significantly varied by education category. Participants with at least some college education reported significantly greater depression knowledge and less stigma surrounding depression and medication than participants with lower education levels. CONCLUSIONS: Primary care settings are often the gateway to identifying undiagnosed mental health disorders, particularly for Hispanic women with comorbid physical health conditions. This study is unique in that it aims to examine the specific role of patient education level as a predictor of mental health literacy. For Hispanic women, understanding the mental health literacy of patients in a healthcare setting may improve quality of care through early detection of symptoms, culturally effective education and subsequent engagement in treatment. TRIAL REGISTRATION: The study was registered with https://clinicaltrials.gov/: NCT02491034 July 2, 2015. PMID- 29788999 TI - The first case of multiple pulmonary granulomas with amyloid deposition in a dental technician; a rare manifestation as an occupational lung disease. AB - BACKGROUND: Occupational lung diseases, such as pneumoconiosis, are one of the health problems of dental workers that have been receiving increasing interest. Pulmonary amyloidosis is a heterogenous group of diseases, and can be classified into primary (idiopathic) and secondary (associated with various inflammatory diseases, hereditary, or neoplastic). To date, the development of pulmonary amyloidosis in dental workers has not been reported. CASE PRESENTATION: A 58-year old Japanese female presented with chest discomfort and low-grade fever that has persisted for 2 months. She was a dental technician but did not regularly wear a dust mask in the workplace. Chest X ray and computed tomography revealed multiple well-defined nodules in both lungs and fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the same lesions with a maximal standardized uptake value (SUV [max]) of 5.6. We next performed thoracoscopic partial resection of the lesions in the right upper and middle lobes. The histological examination of the specimens revealed granuloma formation with foreign body-type giant cells and amyloid deposition that was confirmed by Congo red staining and direct fast scarlet (DFS) staining that produce apple-green birefringence under crossed polarized light. Because there were no other causes underlying the pulmonary amyloidosis, we performed electron probe X-ray microanalysis (EPMA) of the specimens and the result showed silica deposition in the lesions. Based on these results, we finally diagnosed the patient with pulmonary granulomas with amyloid deposition caused by chronic silica exposure. Afterward, her symptoms were improved and the disease has not progressed for 2 years since proper measures against additional occupational exposure were implemented. CONCLUSIONS: Our case presented three important clinical insights: First, occupational exposure to silica in a dental workplace could be associated with the development of amyloid deposition in lung. Second, EPMA was useful to reveal the etiology of amyloid deposition in the lungs. Last, proper protection against silica is important to prevent further progression of the disease. In conclusion, our case suggested that occupational exposure to silica should be considered when amyloid deposition of unknown etiology is found in the lungs of working or retired adults. PMID- 29789000 TI - Spontaneous splenic rupture complicating primary varicella zoster infection: a case report. AB - BACKGROUND: Primary varicella zoster virus (VZV) infection is a common illness, predominantly affecting children. Its course is typically benign, although severe complications have been described. Splenic rupture is an extremely rare and potentially fatal complication of primary VZV infection, with only a handful of cases reported in the literature. CASE PRESENTATION: A 32-year-old Romanian man with no significant past medical history, presented with a 2 day history of sudden onset, worsening generalised abdominal pain and a 1 day history of vomiting. The following day he developed fevers and a generalised widespread erythematous rash consisting of clusters of macules, papules and vesicles at different stages of development. There was no history of sore throat, coryza, arthralgia, myalgia, cough, shortness of breath, weight loss, or night sweats. There was no recent illness and no history of trauma. CT abdomen showed splenic rupture with intra-abdominal haemorrhage. Admission bloods showed anaemia and thrombocytopenia, with haemoglobin 110 g/l and platelets 78 * 109/l. Viral PCR of vesicle fluid from the rash was positive for VZV DNA confirming the clinical diagnosis of primary varicella zoster infection. Viral serology also confirmed recent infection. He was haemodynamically resuscitated, and underwent laparotomy and splenectomy. He was commenced on IV acyclovir and completed a 5 day course. Prior to discharge he was commenced on recommended splenectomy secondary prevention treatment. CONCLUSION: There are several reported complications of varicella infection, more commonly in the immunocompromised population. Spontaneous splenic rupture is an unusual complication of primary VZV infection. Here we report the sixth known case in the literature. Splenic rupture should be considered in cases of primary varicella in young adults presenting with abdominal pain. PMID- 29789001 TI - Dissemination and use of WHO family planning guidance and tools: a qualitative assessment. AB - BACKGROUND: As countries continue to improve their family planning (FP) programmes, they may draw on WHO's evidence-based FP guidance and tools (i.e. materials) that support the provision of quality FP services. METHODS: To better understand the use and perceived impact of the materials and ways to strengthen their use by countries, we conducted qualitative interviews with WHO regional advisors, and with stakeholders in Ethiopia and Senegal who use WHO materials. RESULTS: WHO uses a multi-faceted strategy to directly and indirectly disseminate materials to country-level decision-makers. The materials are used to develop national family planning guidelines, protocols and training curricula. Participants reported that they trust the WHO materials because they are evidence based, and that they adapt materials to the country context (e.g. remove content on methods not available in the country). The main barrier to the use of national materials is resource constraints. CONCLUSIONS: Although the system and processes for dissemination work, improvements might contribute to increased use of the materials. For example, providers may benefit from additional guidance on how to counsel women with characteristics or medical conditions where contraceptive method eligibility criteria do not clearly rule in or rule out a method. PMID- 29788997 TI - 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. AB - Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field. PMID- 29789002 TI - The impact of economic and social factors on the prevalence of hepatitis B in Turkey. AB - BACKGROUND: Viral Hepatitis is one of the major global health problems, affecting millions of people every year. Limited information is available on the impact of social and economic factors on the prevalence of Hepatitis B virus (HBV) in Turkey. This study, contrary to other studies in the literature, was undertaken with the aim of examining the Majority of the excluded data come from the volunteers. METHODS: There are medical and the social-economic factors affecting the prevalence of HBV. This research, while taking medical factors as control variables, clarify the social and economic factors affecting the prevalence of HBV by utilising clinical data with the use of the Binary Probit Model (BPM). The BPM estimation is a powerful tool to determine not only the factors but explain also the exact impacts of each factor. RESULTS: The estimations of the BPM shows that economic and social variables such as age, gender, migration, education, awareness, social welfare, occupation are very important factors for determining HBV prevalence. Compared to the youngest population, the 46 to 66+ age group has a higher prevalence of HBV. The male respondents were 5% more likely to develop HBV compared to females. When region-specific differences are taken into account, migrating from the poorest parts of the country such as the eastern and south eastern regions of Turkey are approximately 16% more likely to be infected. The welfare indicators such as a higher number of rooms in the respondent's house or flat decreases the probability of having HBV and, relatively higher income groups are less likely to develop HBV compared to labourers. The Self-employed/Business owner/Public sector worker category are approximately 10% less likely to develop HBV. When people are aware of the methods of prevention of HBV, they are 6% less likely to be infected. Previous HBV infection history increases the probability of having HBV again B by 17%. CONCLUSIONS: These findings strongly suggest that the impact of social and economic factors on the prevalence of HBV is vital. Any improvements in these factors are likely to reduce prevalence of HBV. PMID- 29789003 TI - Mothers' autonomy and childhood stunting: evidence from semi-urban communities in Lao PDR. AB - BACKGROUND: Childhood stunting (height-for-age z-scores below - 2), a form of chronic undernutrition, remains a global health burden. Although a growing literature has examined the association between mothers' autonomy and childhood stunting, these studies have been limited to countries in South Asia or Sub Saharan Africa where women have relatively lower social status than do men. Little research has analyzed the effect of mothers' autonomy on childhood stunting in Lao PDR, where women's social status is relatively high compared to that in other countries. METHODS: We conducted a cross-sectional questionnaire and body scale measurement targeting 100 mothers and their 115 children (<5 years old) from semi-urban communities in Lao PDR, which is the country with the highest prevalence of childhood stunting in the Indochina region. As dimensions of women's autonomy, we measured self-esteem, self-efficacy, decision-making power, freedom of mobility, and control of money. We then analyzed how each dimension was associated with the likelihood of childhood stunting. RESULTS: The likelihood of childhood stunting was significantly lower if mothers had higher self-efficacy for health care (OR = 0.15, p = 0.007), self-esteem (OR = 0.11, p = 0.025), or control of money (OR = 0.11, p = 0.041). In contrast, mothers' decision-making power and freedom of mobility were not significantly associated with childhood stunting. CONCLUSIONS: We clarified which dimensions of women's autonomy were associated with childhood stunting in Lao PDR. A closer examination of mothers' autonomy will aid proper understanding of the determinants of childhood stunting. PMID- 29789004 TI - A population-based study of the risk of osteoporosis and fracture with dutasteride and finasteride. AB - BACKGROUND: Dutasteride is a potent inhibitor of 5-alpha reductase enzymes that reduces concentrations of dihydrotestosterone to a greater extent than finasteride. Whether this has adverse implications for bone health is unknown. We compared the risk of osteoporosis and fractures in older men treated with dutasteride or finasteride. METHODS: We conducted a population-based retrospective cohort study with high-dimensional propensity score matching of Ontario men aged 66 years or older who started treatment with dutasteride or finasteride between January 1, 2006 and December 31, 2012. The primary outcome was a diagnosis of osteoporosis within 2 years of treatment initiation. A secondary outcome was osteoporotic or fragility fractures. RESULTS: We studied 31,615 men treated with dutasteride and an equal number of men treated with finasteride. Dutasteride-treated patients had a lower incidence of osteoporosis than those receiving finasteride [2.2 versus 2.6 per 100 person years; hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.72 to 0.93]. This effect was no longer statistically significant following adjustment for specialty of prescribing physician (HR 0.90; 95% CI 0.78 to 1.02)]. There was no differential risk of fractures with dutasteride (HR 1.04; 95% 0.86 to 1.25). CONCLUSIONS: Despite differential effects on 5-alpha reductase, dutasteride is not associated with an increased risk of osteoporosis or fractures in older men relative to finasteride. These findings suggest that dutasteride does not adversely affect bone health. PMID- 29789005 TI - Ultrasonography in diagnosis and analysis of chronic pain following anterior open inguinal herniorrhaphy. AB - BACKGROUND: Chronic pain as a complication following inguinal herniorrhaphy has attracted increasing attention in recent years. There is evidence that the chronic pain seriously affects patients' quality of life. However, there are few imaging studies and diagnostic techniques of the chronic pain. The aim of this study is to explore the etiology and to analysis ultrasonographic imaging description of chronic pain following anterior open inguinal herniorrhaphy. METHODS: One hundred fifty two patients with the chronic pain following anterior open inguinal herniorrhaphy were performed by ultrasonography to identify the main causes of postoperative chronic pain. Positive ultrasonic diagnoses were confirmed to be correct by the pain relieved when the patients underwent re operation and other clinical operations. Positive diagnoses which appeared simultaneously were grouped for pairwise comparisons. RESULTS: Two hundred sixteen positive ultrasonic diagnoses, 12 categories of postoperative chronic pain were found. They were encapsulated effusion, scrotal wall edema, testitis, hydrocele testis, restricted motion of spermatic cord at the reconstructed deep inguinal ring, varicocele, scar sutured into pubic tubercle, shrinking mesh, accumulational mesh or mesh plug, recurrent hernia, cyst of spermatic cord and epididymal cyst. In the pairwise comparison groups, encapsulated effusion with scrotal wall edema, varicocele with restricted motion of spermatic cord at the reconstructed deep inguinal ring, and shrinking mesh with recurrent hernia had significant differences in each intragroup comparisons(P < 0.05). CONCLUSIONS: Ultrasonography provieds important value in the diagnosis of chronic pain following anterior open inguinal herniorrhaphy. Some positive diagnoses occur simultaneously, which is necessary for doctors to consider comprehensively. PMID- 29789006 TI - Outcomes of lung transplantation in adults with bronchiectasis. AB - BACKGROUND: Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here. METHODS: A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013. RESULTS: Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths. CONCLUSIONS: Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common. PMID- 29789007 TI - Site-dependent differences in the composite fibers of male pelvic plexus branches: an immunohistochemical analysis of donated elderly cadavers. AB - BACKGROUND: Although the pelvic autonomic plexus branches are considered to be a mixture of sympathetic and parasympathetic nerves, little is known regarding the composite fibers of the pelvic plexus branches. This study aimed to investigate the immunohistochemical features of sympathetic and parasympathetic nerves in the pelvic autonomic plexus branches. METHODS: Using 10 donated elderly male cadavers, the detailed topohistology of nerve fibers at and around the bladder, seminal vesicle, prostate, and rectum was examined. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers; tyrosine hydroxylase (TH) was used as a sympathetic nerve marker. The myenteric plexus of the colon was utilized as a positive control. RESULTS: Most nerve fibers in the bladder, seminal vesicle, prostate, and rectum were both nNOS- and TH-positive. Thus, pelvic plexus branches were classified into two types: 1) triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -) and 2) double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -). Notably, triple-positive nerves were localized within the posterosuperior part of the plexus (near the rectum) and travelled anteroinferiorly toward the posterolateral corner of the prostate. The posteriorly and inferiorly located nerves were predominantly composed of parasympathetic, rather than sympathetic, fibers. In contrast, nerve fibers within and along the bladder and seminal vesicle contained either no or few VIP-positive nerves. These superiorly located nerves were characterized by clear sympathetic nerve dominance. CONCLUSIONS: The nerves of the pelvic plexus branches were clearly classified into nerves around the bladder and seminal vesicle (VIP-negative) and nerves around the prostate (VIP-positive). Although nNOS- and VIP-positive nerve fibers are candidate cavernous nerves, cavernous nerve identity cannot be definitively concluded for these nerves in the periprostatic region. PMID- 29789009 TI - Correction to: Antibiotic resistance pattern and virulence genes content in avian pathogenic Escherichia coli (APEC) from broiler chickens in Chitwan, Nepal. AB - The original article [1] contains errors in author panels and their contributions, errors in both the Methodology and the Results sections, and errors with respect to funding sources. The affected sections of the manuscript and their respective regions of corrected text can be viewed ahead. PMID- 29789008 TI - Pharmacological effects of N-[2-[[2-[2-[(2,6 dichlorophenyl)amino]phenyl]acetyl]oxy]ethyl]hyaluronamide (diclofenac Etalhyaluronate, SI-613), a novel sodium hyaluronate derivative chemically linked with diclofenac. AB - BACKGROUND: Osteoarthritis (OA) is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have investigated the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), which is a potentially safer and more effective treatment for OA knee pain. In this study, we evaluated the pharmacological effects of SI-613 in experimental arthritis models. METHODS: We compared the analgesic and anti-inflammatory effects of intra-articularly administered SI-613, hyaluronic acid (HA), and of orally administered diclofenac sodium (DF-Na) in rat silver nitrate-induced arthritis model and rabbit antigen induced arthritis model. RESULTS: A single intra-articular (IA) administration of SI-613 significantly suppressed pain responses in rats in a dose-dependent manner. The analgesic effects were greater than those of HA, a mixture of DF-Na and HA, or an oral once-daily administration of DF-Na. In the rabbit arthritis model, SI-613 significantly reduced knee joint swelling compared with that in the control group on day 1 after a single IA injection. This significant anti inflammatory effect was observed until day 28. In the pharmacokinetic study, the DF concentration in the synovium after SI-613 administration reached its maximum concentration of 311.6 ng/g on day 1, and gradually declined to 10 ng/g by day 28. It fell below the lower limit of quantification on day 35. Thus, a clear correlation was found between pharmacokinetics and pharmacodynamics. These results demonstrate that SI-613 exerts its long-lasting and potent anti inflammatory effect by sustainable release of DF in the knee joint tissues. CONCLUSION: A single IA injection of SI-613 was shown to exert analgesic and anti inflammatory effects for 28 days in non-clinical pharmacological studies, suggesting that SI-613 will be a promising candidate in the treatment of osteoarthritis pain. PMID- 29789010 TI - Perceived behavioural predictors of late initiation to HIV/AIDS care in Gurage zone public health facilities: a cohort study using health belief model. AB - OBJECTIVE: The study was aimed to measure incidence density rate and identify perceived behavioural believes of late initiation to HIV/AIDS care in Gurage zone public health facilities from September 2015 to November 2016. RESULTS: The incidence density rates of late initiation to HIV/AIDS care were 2.21 per 100 person-months of observation. HIV positive individuals who did not perceived susceptibility were 8.46 times more likely delay to start HIV/AIDS care than their counter parts [OR = 8.46 (95% CI 3.92, 18.26)]. HIV infected individuals who did not perceived severity of delayed ART initiation were 6.13 time more likely to delay than HIV infected individuals who perceived its severity [OR = 6.13 (95% CI 2.95, 12.73)]. HIV positive individuals who didn't have self efficacy were 2.35 times more likely delay to start HIV/AIDS care than HIV positive individuals who have self-efficacy [OR = 2.35 (95% CI 1.09, 5.05)]. CONCLUSIONS: The study revealed that high incidence density rates of delayed initiation for HIV care and variations were explained by poor wealth, and perceived threat and benefit. Therefore, interventions should be designed to initiate care at their diagnosis time. PMID- 29789011 TI - Novel Phenoxazinones as potent agonist of PPAR-alpha: design, synthesis, molecular docking and in vivo studies. AB - BACKGROUND: The use of statin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for the treatment of dyslipidemia has been associated with dose limiting hepatoxicity, mytotoxicity and tolerability due to myalgias thereby necessitating the synthesis of new drug candidates for the treatment of lipid disorder. METHODS: The reaction of appropriate benzenesulphonamide with substituted phenoxazinone in the presence of phenylboronic acid gave the targeted compounds. The molecular docking study were carried out using autodock tool against peroxisome proliferator activated receptor alpha. The in vivo lipid profile were assayed using conventional methods. The kidney and liver function test were carried out to assess the effect of the derivatives on the organs. The LD50 of the most active derivatives were determined using mice. RESULTS: The targeted compounds were successfully synthesized in excellent yields and characterized using spectroscopic techniques. The results of the molecular docking experiment showed that they were good stimulant of peroxisome proliferator activated receptor alpha. Compound 9f showed activity at Ki of 2.8 nM and binding energy of 12.6 kcal/mol. All the compounds tested reduced triglyceride, total cholesterol, low density lipoprotein cholesterol and very low density lipoprotein cholesterol level in the mice model. Some of the reported compounds also increased high density lipoprotein cholesterol level in the mice. The compounds did not have appreciable effect on the kidney and liver of the mice used. The LD50 showed that the novel compounds have improved toxicity profile. CONCLUSION: The synthesis of fifteen new derivatives of carboxamides bearing phenoxazinone and sulphonamide were successful. The compounds possessed comparable activity to gemfibrozil. The reported compounds had better toxicity profile than gemfibrozil and could serve as a replacement for the statins and fibrate class of lipid agents. PMID- 29789012 TI - Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury. AB - BACKGROUND: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio indicator of inflammation. We hypothesized the efficacy of novel TNF receptor (TNF-R) inhibitors could be screened using post-traumatic sleep and that these novel compounds would improve functional recovery following diffuse TBI in the mouse. METHODS: Three inhibitors of TNF-R activation were synthesized based on the structure of previously reported TNF CIAM inhibitor F002, which lodges into a defined TNFR1 cavity at the TNF-binding interface, and screened for in vitro efficacy of TNF pathway inhibition (IkappaB phosphorylation). Compounds were screened for in vivo efficacy in modulating post-traumatic sleep. Compounds were then tested for efficacy in improving functional recovery and verification of cellular mechanism. RESULTS: Brain-injured mice treated with Compound 7 (C7) or SGT11 slept significantly less than those treated with vehicle, suggesting a therapeutic potential to target neuroinflammation. SGT11 restored cognitive, sensorimotor, and neurological function. C7 and SGT11 significantly decreased cortical inflammatory cytokines 3 h post-TBI. CONCLUSIONS: Using sleep as a bio indicator of TNF-R-dependent neuroinflammation, we identified C7 and SGT11 as potential therapeutic candidates for TBI. PMID- 29789013 TI - Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors. AB - BACKGROUND: Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors. METHODS: In total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 in these cases. Cases demonstrating >=5% tumor cell expression or any expression (> 1%) of PD-L1 on immune cells were considered positive. CD8+ TILs both within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for each case. RESULTS: Positive expression of PD-L1 was observed in 72 cases (45.3%), including 9 cases (5.7%) with expression exclusively on tumor cells, 46 cases (28.9%) with expression exclusively on immune cells, and 17 cases (10.7%) with the expression on tumor cells and immune cells. PD-L1 expression was associated with necrosis (p < 0.001), high pathologic grade (p < 0.001) and histologic type (p < 0.001). No correlation was observed with overall survival (OS) (p = 0.158) or progression-free survival (PFS) (p = 0.315). In contrast, higher CD8+ T cell density was associated with the absence of vascular invasion (p = 0.004), histologic type (p = 0.005), negative lymph node metastasis (p = 0.005) and lower clinical staging (p = 0.007). Moreover, multivariate analysis revealed that CD8+ stromal TIL was an independent prognostic factor for improved OS (p = 0.009) and PFS (p = 0.002). CONCLUSION: PD-L1 was expressed in approximately half of the PNETs. The majority of the expression was observed in immune cells. Positive expression of PD-L1 showed no correlation with OS or PFS, while higher CD8+ TILs within stroma was proved to be an independent prognostic factor for favorable OS and PFS of PNETs. PMID- 29789016 TI - Unraveling bacterial fingerprints of city subways from microbiome 16S gene profiles. AB - BACKGROUND: Microbial communities can be location specific, and the abundance of species within locations can influence our ability to determine whether a sample belongs to one city or another. As part of the 2017 CAMDA MetaSUB Inter-City Challenge, next generation sequencing (NGS) data was generated from swipe samples collected from subway stations in Boston, New York City hereafter New York, and Sacramento. DNA was extracted and Illumina sequenced. Sequencing data was provided for all cities as part of 2017 CAMDA contest challenge dataset. RESULTS: Principal component analysis (PCA) showed clear clustering of the samples for the three cities, with a substantial proportion of the variance explained by the first three components. We ran two different classifiers and results were robust for error rate (< 6%) and accuracy (> 95%). The analysis of variance (ANOVA) demonstrated that overall, bacterial composition across the three cities is significantly different. A similar conclusion was reached using a novel bootstrap based test using diversity indices. Last but not least, a co-abundance association network analyses for the taxonomic levels "order", "family", and "genus" found different patterns of bacterial networks for the three cities. CONCLUSIONS: Bacterial fingerprint can be useful to predict sample provenance. In this work prediction of provenance reported with over 95% accuracy. Association based network analysis, emphasized similarities between the closest cities sharing common bacterial composition. ANOVA showed different patterns of bacterial amongst cities, and these findings strongly suggest that bacterial signature across multiple cities are different. This work advocates a data analysis pipeline which could be followed in order to get biological insight from this data. However, the biological conclusions from this analysis is just an early indication out of a pilot microbiome data provided to us through CAMDA 2017 challenge and will be subject to change as we get more complete data sets in the near future. This microbiome data can have potential applications in forensics, ecology, and other sciences. REVIEWERS: This article was reviewed by Klas Udekwu, Alexandra Graf, and Rafal Mostowy. PMID- 29789014 TI - A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases. AB - BACKGROUND: Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. METHODS: A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. RESULTS: Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. CONCLUSIONS: There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care. PMID- 29789015 TI - Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. AB - Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments. PMID- 29789018 TI - Pain clinic definitions in the medical literature and U.S. state laws: an integrative systematic review and comparison. AB - BACKGROUND: In response to widespread opioid misuse, ten U.S. states have implemented regulations for facilities that primarily manage and treat chronic pain, called "pain clinics." Whether a clinic falls into a state's pain clinic definition determines the extent to which it is subject to oversight. It is unclear whether state pain clinic definitions model those found in the medical literature, and potential differences lead to discrepancies between scientific and professionally guided advice found in the medical literature and actual pain clinic practice. Identifying discrepancies could assist states to design laws that are more compatible with best practices suggested in the medical literature. METHODS: We conducted an integrative systematic review to create a taxonomy of pain clinic definitions using academic medical literature. We then identified existing U.S. state pain clinic statutes and regulations and compared the developed taxonomy using a content analysis approach to understand the extent to which medical literature definitions are reflected in state policy. RESULTS: In the medical literature, we identified eight categories of pain clinic definitions: 1) patient case mix; 2) single-modality treatment; 3) multidisciplinary treatment; 4) interdisciplinary treatment; 5) provider supervision; 6) provider composition; 7) marketing; and 8) outcome. We identified ten states with pain clinic laws. State laws primarily include the following definitional categories: patient case mix; single-modality treatment, and marketing. Some definitional categories commonly found in the medical literature, such as multidisciplinary treatment and interdisciplinary treatment, rarely appear in state law definitions. CONCLUSIONS: This is the first study to our knowledge to develop a taxonomy of pain clinic definitions and to identify differences between pain clinic definitions in U.S. state law and medical literature. Future work should explore the impact of different legal pain clinic definitions on provider decision-making and state-level health outcomes. PMID- 29789017 TI - Leveraging routine clinical materials and mobile technology to assess CBT fidelity: the Innovative Methods to Assess Psychotherapy Practices (imAPP) study. AB - BACKGROUND: Identifying scalable strategies for assessing fidelity is a key challenge in implementation science. However, for psychosocial interventions, the existing, reliable ways to test treatment fidelity quality are often labor intensive, and less burdensome strategies may not reflect actual clinical practice. Cognitive behavioral therapies (CBTs) provide clinicians with a set of effective core elements to help treat a multitude of disorders, which, evidence suggests, need to be delivered with fidelity to maximize potential client impact. The current "gold standard" for rating CBTs is rating recordings of therapy sessions, which is extremely time-consuming and requires a substantial amount of initial training. Although CBTs can vary based on the target disorder, one common element employed in most CBTs is the use of worksheets to identify specific behaviors and thoughts that affect a client's ability to recover. The present study will develop and evaluate an innovative new approach to rate CBT fidelity, by developing a universal CBT scoring system based on worksheets completed in therapy sessions. METHODS: To develop a scoring system for CBT worksheets, we will compile common CBT elements from a variety of CBT worksheets for a range of psychiatric disorders and create adherence and competence measures. We will collect archival worksheets from past studies to test the scoring system and assess test-retest reliability. To evaluate whether CBT worksheet scoring accurately reflects clinician fidelity, we will recruit clinicians who are engaged in a CBT for depression, anxiety, and/or posttraumatic stress disorder. Clinicians and clients will transmit routine therapy materials produced in session (e.g., worksheets, clinical notes, session recordings) to the study team after each session. We will compare observer-rated fidelity, clinical notes, and fidelity-rated worksheets to identify the most effective and efficient method to assess clinician fidelity. Clients will also be randomly assigned to either complete the CBT worksheets on paper forms or on a mobile application (app) to learn if worksheet format influences clinician and client experience or differs in terms of reflecting fidelity. DISCUSSION: Scoring fidelity using CBT worksheets may allow clinics to test fidelity in a short and effective manner, enhancing continuous quality improvement in the workplace. Clinicians and clinics can use such data to improve clinician fidelity in real time, leading to improved patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03479398 . Retrospectively registered March 20, 2018. PMID- 29789019 TI - Adolescents' perceptions and experiences of pregnancy in refugee and migrant communities on the Thailand-Myanmar border: a qualitative study. AB - BACKGROUND: Adolescent pregnancy remains a global health concern, contributing to 11% of all births worldwide and 23% of the overall burden of disease in girls aged 15-19 years. Premature motherhood can create a negative cycle of adverse health, economic and social outcomes for young women, their babies and families. Refugee and migrant adolescent girls might be particularly at risk due to poverty, poor education and health infrastructure, early marriage, limited access to contraception and traditional beliefs. This study aims to explore adolescents' perceptions and experiences of pregnancy in refugee and migrant communities on the Thailand-Myanmar border. METHODS: In June 2016 qualitative data were collected in one refugee camp and one migrant clinic along the Thailand-Myanmar border by conducting 20 individual interviews with pregnant refugee and migrant adolescents and 4 focus group discussions with husbands, adolescent boys and non pregnant girls and antenatal clinic staff. Inductive thematic analysis was used to identify codes and themes emerging from the data. RESULTS: Study participants perceived adolescent pregnancy as a premature life event that could jeopardise their future. Important themes were premarital sex, forced marriage, lack of contraception, school dropout, fear of childbirth, financial insecurity, support structures and domestic violence. Supportive relationships with mothers, husbands and friends could turn this largely negative experience into a more positive one. The main underlying reasons for adolescent pregnancy were associated with traditional views and stigma on sexual and reproductive health issues, resulting in a knowledge gap on contraception and life skills necessary to negotiate sexual and reproductive choices, in particular for unmarried adolescents. CONCLUSIONS: Adolescents perceive pregnancy as a challenging life event that can be addressed by developing comprehensive adolescent-friendly sexual and reproductive health services and education in refugee and migrant communities on the Thailand-Myanmar border. Creating a more tolerant and less stigmatising environment in these communities and their governing bodies will help to achieve this goal. PMID- 29789020 TI - Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events. AB - BACKGROUND: Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. METHODS: We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. RESULTS: We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). CONCLUSIONS: Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population. PMID- 29789023 TI - Iron supplementation has minor effects on gut microbiota composition in overweight and obese women in early pregnancy. AB - Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks' gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks' gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (>=60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5-10) v. 60 (IQR 60-60) mg/d in the high group (P<0.001). Dietary Fe intake did not differ between the groups (10.0 (IQR 7.4-13.3) v. 9.8 (IQR 8.2-13.2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks' gestation. PMID- 29789022 TI - Healthcare disparities amongst vulnerable populations of Arabs and Jews in Israel. AB - The complex nature of studying health and healthcare disparities in general, and in the context of the Israeli healthcare system in particular, is depicted in two recent IJHPR articles. The first examines Emergency Department (ED) waiting times in a tertiary children's hospital and the second examines disparities in the health care for people with schizophrenia of an ethnic-national minority. Contrary to other Israeli studies on wide disparities in health and healthcare, these studies show no disparities - ED waiting times did not differ among Arab and Jewish children and report no differences in performance of Hemoglobin A1C tests or in surgical interventions in patients with cardiovascular disease between Arabs and Jews with schizophrenia. Thus, the studies reflect areas of equitable health care delivery within the Israeli healthcare system.Future studies should account for the fact that the phenomena of health and healthcare disparities is complex and should utilize rigorous methodologies to take into consideration the various factors that may affect the manifestation of differences amongst population groups. As a result, they may help detect disparities which may otherwise be missed. PMID- 29789021 TI - Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study. AB - INTRODUCTION: Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients. METHODS: Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF). Amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) were used to identify the T790M mutation in ctDNA. Prognosis was analyzed with Kaplan-Meier methods. RESULTS: Overall concordance between the two methods was 78.3%. According to both ARMS and ddPCR, patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups (P < 0.001), and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups (P < 0.001). AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+ patients in all groups who had progressed on EGFR-TKIs; for other treatments, the prognosis of T790M- patient subgroups varied. CONCLUSIONS: The present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influence treatment selection and prognosis. PMID- 29789024 TI - A STUDY OF THE HERITABILITY OF INTELLIGENCE IN SUDAN. AB - SummaryIntelligence was assessed using the Standard Progressive Matrices in 316 MZ and 550 same-sex DZ twins with a mean age of 10 years in Sudan. Heritability was estimated at 0.172 and shared environmental influences at 0.596. PMID- 29789025 TI - Tethered Balloon Technology in Design Solutions for Rescue and Relief Team Emergency Communication Services. AB - The actions taken at the initial times of a disaster are critical. Catastrophe occurs because of terrorist acts or natural hazards which have the potential to disrupt the infrastructure of wireless communication networks. Therefore, essential emergency functions such as search, rescue, and recovery operations during a catastrophic event will be disabled. We propose tethered balloon technology to provide efficient emergency communication services and reduce casualty mortality and morbidity for disaster recovery. The tethered balloon is an actively developed research area and a simple solution to support the performance, facilities, and services of emergency medical communication. The most critical requirement for rescue and relief teams is having a higher quality of communication services which enables them to save people's lives. Using our proposed technology, it has been reported that the performance of rescue and relief teams significantly improved. OPNET Modeler 14.5 is used for a network simulated with the help of ad hoc tools (Disaster Med Public Health Preparedness. 2018;page 1 of 8). PMID- 29789026 TI - Communication Barrier in Family Linked to Increased Risks for Food Insecurity among Deaf Adults who use American Sign Language - CORRIGENDUM. PMID- 29789027 TI - Ethanolamine enhances intestinal functions by altering gut microbiome and mucosal anti-stress capacity in weaned rats. AB - Ethanolamine (Etn) contained in milk is the base constituent of phosphatidylethanolamine and is required for the proliferation of intestinal epithelial cells and bacteria, which is important for maintenance of the gut microbiome and intestinal development. The present study investigated the effect of Etn on intestinal function and microbiome using 21-d-old Sprague-Dawley rats treated with 0, 250, 500 and 1000 MUm Etn in drinking water for 2 weeks immediately after weaning. Growth performance, intestinal morphology, antioxidant capacity and mucosal immunity, as well as gut microbiota community composition, were evaluated. Metagenomic prediction and metabolic phenotype analysis based on 16S RNA sequencing were also carried out to assess changes in metabolic functions. We found that weaned rats administered 500 MUm Etn enhanced mucosal antioxidant capacity, as evidenced by higher superoxide dismutase and glutathione peroxidase levels in the jejunum (P<0.05) compared with those in the control group. Predominant microbes including Bacteroidetes, Proteobacteria, Elusimicrobia and Tenericutes were altered by different levels of Etn compared with the control group. An Etn concentration of 500 um shifted colonic microbial metabolic functions that are in favour of lipid- and sugar-related metabolism and biosynthesis. Etn also altered the metabolic phenotypes such as anaerobic microbial counts, and oxidative stress tolerance at over 250 um. This is the first report for a role of Etn in modifying gut microbiota and intestinal functions. Our findings highlighted the important role of Etn in shaping gut microbial community and promotes intestinal functions, which may provide a better insight of breast-feeding to infant's gut health. PMID- 29789028 TI - Association between serum magnesium and blood lipids: influence of type 2 diabetes and central obesity. AB - To assess the changes in the relationship between serum Mg and blood lipids of Chinese adults with type 2 diabetes (T2D) or central obesity, a total of 8163 subjects (mean age 59.6 years, 54.9 % men) were analysed. Participants were classified according to blood Mg (below 0.65 mmol/l, 0.65-0.95 mmol/l and above 0.95 mmol/l), T2D (yes/no) and central obesity (yes/no). Blood lipids (TAG, total cholesterol (TC), HDL-cholesterol and LDL-cholesterol) were determined by standardised methods and conditions. A significant increase in blood lipids, with the exception of HDL-cholesterol, across progressive Mg groups in all subjects was noted (P0.05). TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D than those without T2D (P<0.05). Multivariable models for TAG and LDL-cholesterol failed to attain statistical significance in diabetics, by using a generalised linear or parsimonious model. TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D or central obesity. Blood lipids, with the exception of HDL cholesterol, were associated with serum Mg, but this association was somehow influenced by T2D in LDL-cholesterol. In addition, multivariable models for both TAG and LDL-cholesterol failed to attain statistical significance among subjects with T2D, different from subjects without T2D. PMID- 29789030 TI - Yes, not now, or never: an analysis of reasons for refusing or accepting emergency department-based take-home naloxone. AB - CLINICIAN'S CAPSULE What is known about the topic? Not all patients at risk of opioid overdose accept emergency department (ED)-based take-home naloxone (THN). What did this study ask? Why do at-risk ED patients refuse or accept THN? What did this study find? Those refusing THN felt: 1) not at risk of overdose; or 2) their ED visit was not the right time or place for THN. Those accepting THN wanted to save the lives of others. Why does this study matter to clinicians? Those refusing ED THN may accept THN elsewhere if referred to appropriate community services for overdose risk education and THN distribution. PMID- 29789029 TI - Pediatric Brain Development in Down Syndrome: A Field in Its Infancy. AB - OBJECTIVES: As surprisingly little is known about the developing brain studied in vivo in youth with Down syndrome (DS), the current review summarizes the small DS pediatric structural neuroimaging literature and begins to contextualize existing research within a developmental framework. METHODS: A systematic review of the literature was completed, effect sizes from published studies were reviewed, and results are presented with respect to the DS cognitive behavioral phenotype and typical brain development. RESULTS: The majority of DS structural neuroimaging studies describe gross differences in brain morphometry and do not use advanced neuroimaging methods to provide nuanced descriptions of the brain. There is evidence for smaller total brain volume (TBV), total gray matter (GM) and white matter, cortical lobar, hippocampal, and cerebellar volumes. When reductions in TBV are accounted for, specific reductions are noted in subregions of the frontal lobe, temporal lobe, cerebellum, and hippocampus. A review of cortical lobar effect sizes reveals mostly large effect sizes from early childhood through adolescence. However, deviance is smaller in adolescence. Despite these smaller effects, frontal GM continues to be largely deviant in adolescence. An examination of age-frontal GM relations using effect sizes from published studies and data from Lee et al. (2016) reveals that while there is a strong inverse relationship between age and frontal GM volume in controls across childhood and adolescence, this is not observed in DS. CONCLUSIONS: Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018, 24, 966-976). PMID- 29789032 TI - Neuropsychological correlates of instrumental activities of daily living in neurocognitive disorders: a possible role for executive dysfunction and mood changes. AB - ABSTRACTSince baseline executive dysfunction predicts worsening Instrumental Activities of Daily Living (i-ADL) over time and progression to Alzheimer's Disease (AD), we aimed to analyze the role of neuropsychological variables to outline which factors can contribute to functional impairment. Specific attention to executive functions (EFs) has been given.A total of 144 subjects complaining of different cognitive deficits - ranging from "MCI likely due to AD" to "mild AD patients" - underwent an overall neuropsychological assessment. The Behavioral Assessment of the Dysexecutive Syndrome was used to analyze EFs. We conducted multiple linear regression analyses to study whether the level of independent living skills - assessed with the Lawton-scale - could be associated with cognitive and behavioral measurements.We found a significant association between i-ADL and specific EFs measured by Rule Shift Cards (p = 0.04) and Modified Six Elements (p = 0.02). Moreover, considering i-ADL scores, we observed an involvement of mood changes and a reduced awareness of deficits in terms of Hamilton Depression Rating Scale (p = 0.02) and Awareness of Deficit Questionnaire - Dementia scale (p < 0.0001), respectively.Our results suggest the importance of considering the association between a reduction in i-ADL and executive dysfunction in patients who have AD etiopathology, for which the ability to inhibit a response, self-monitoring, set-shifting and mood deflection play a key role. Besides, no straightforward associations between i-ADL scores and global cognition, memory, language comprehension, attention, and perspective taking abilities were found. PMID- 29789031 TI - Diurnal behaviors and herd characteristics of dairy cows housed in a compost bedded pack barn system under hot and humid conditions. AB - With international demand for production systems aimed at thermal comfort and animal welfare, milk producers have become increasingly interested in compost barns. However, doubts about the behavioral aspects of cows in tropical and subtropical climates remain, because the compost barn system offers a larger bed area per animal at a lower stocking rate. The objective of this study was to evaluate whether the diurnal behaviors, hygiene and lameness of crossbred dairy cows are influenced by different number of lactations when housed in a compost bedded pack barn system under hot and humid conditions. Crossbred cows (Holstein and Jersey), which were divided into two treatments based on number of lactations (primiparous and multiparous cows), were evaluated during lactation (n=12). The study was conducted from September 2015 to February 2016 in a compost barn in the southwest region of the state of Parana, Brazil. Daytime behavior was observed between milking schedules using focal observations with 0/1 sampling. Cow hygiene and lameness were evaluated using subjective scores ranging from 1 to 4 and 1 to 5, respectively. Animal behavior and welfare was analyzed using Bayesian inference with a mixed effects model. The probabilities of dyspnea and pushing behaviors were higher (P<0.05) in multiparous cows, and the probability increased during the hottest hours of the day. For both multiparous and primiparous cows, the agonistic behaviors of pushing, butting and chasing peaked during the afternoon. Eating behaviors had the highest likelihood values (0.8 at 0800 h). The cows preferred to remain lying down in the morning, while rest and standing rumination were preferred in the afternoon. Primiparous cows were cleaner than multiparous cows, and the hygiene score for this group was significantly lower (P<0.05). The hygiene and lameness scores for all animals were low, and the highest scores were 1 and 2. In conclusion, multiparous cows exhibited more frequent agonistic behaviors during the hottest hours of the day. Regarding hygiene and lameness scores, multiparous cows exhibited a higher degree of dirtiness compared with the primiparous cows. PMID- 29789033 TI - The neurological examination adapted for neuropsychiatry. AB - The neuropsychiatric examination includes standard neurological and cognitive examination techniques with several additional observations and tasks designed to capture abnormalities common among patients with neuropsychiatric disorders or neurocognitive complaints. Although useful as a screening tool, a single standardized rating scale such as the Mini Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) is insufficient to establish a neuropsychiatric diagnosis. Extra attention is paid to findings commonly seen in the setting of psychiatric disorders, dementias, movement disorders, or dysfunction of cortical or subcortical structures. Dysmorphic features, dermatologic findings, neurodevelopmental signs, signs of embellishment, and expanded neurocognitive testing are included. The neuropsychiatric clinician utilizes the techniques described in this article to adapt the examination to each patient's situation, choosing the most appropriate techniques to supplement the basic neurological and psychiatric examinations in support of diagnostic hypotheses being considered. The added examination techniques facilitate diagnosis of neurocognitive disorders and enable neuropsychiatric formulation. PMID- 29789034 TI - Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. AB - Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes. PMID- 29789035 TI - The effect of transportation and lairage on faecal shedding and carcass contamination with Escherichia coli O157 and O26 in very young calves in New Zealand. AB - The effect of transportation and lairage on the faecal shedding and post slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4-7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal-oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves. PMID- 29789036 TI - Dietary CP and amino acid restriction has a different impact on the dynamics of protein, amino acid and fat deposition in entire male, castrated and female pigs. AB - Breeding efforts over the last decades altered markedly empty body (EB) composition of pigs. This study aimed to re-evaluate the dynamics of changes in the composition and deposition rate of fat, protein and amino acids (AA) in the EB from birth to 140 kg BW depending on the dietary CP and AA supply in a current pig genotype. In the experiment 66 entire male, 58 castrated and 66 female Swiss Large White pigs were used. From 20 kg BW onwards, they had either ad libitum access to a control (C) diet or a diet (LP) compared to diet C only 80% of CP, lysine, methione+cystine, threonine and tryptophan. The EB composition was determined at birth on eight boars and eight females, at 10 and 20 kg BW on two boars, two castrates and two females, and at 20 kg intervals from 40 to 140 kg BW, on four pigs per gender and dietary treatment. Each EB fraction was weighed and analysed for protein, fat and AA profile. The AA-to-lysine ratio was calculated and the different chemical component contents were fitted to allometric regressions. Overall, C-boars had the greatest EB protein and AA content and deposition rates, and lowest fat content and deposition rates. At the beginning of the grower period, LP-castrates and females displayed the lowest protein and AA and the highest fat deposition rates. However, compared with their counterparts in the C-group, in LP-castrates and females protein and AA deposition rates were greater above 64 and 40 kg EB weight, respectively, whereas fat deposition rates was lower above 80 kg EB weight. Thus, there seems a great potential to optimise protein and AA efficiency especially in the finisher period in castrates and females. Important individual variations were found in the essential AA-to-lysine ratio of the EB. Phenylalanine and threonine-to-lysine ratios decreased with increasing EB weight. Valine- and threonine-to-lysine ratios in C-castrates and C-females were 5% and 4% greater than recently reported by the National Research Council (NRC) whereas cysteine-, methionine- and tyrosine-to-lysine ratios were lower by 34%, 25% and 10%, respectively. The clear differences found between the EB AA-to-lysine ratios in the present study and the NRC might partly be explained by the genotype and the temporal changes in the relative weight of each EB fraction or changes in the AA profile. Nevertheless, these findings on changes in the essential AA profile of tissue protein warrant further studies. PMID- 29789037 TI - A comparison of statistical and machine-learning techniques in evaluating the association between dietary patterns and 10-year cardiometabolic risk (2002 2012): the ATTICA study. AB - Statistical methods are usually applied in examining diet-disease associations, whereas factor analysis is commonly used for dietary pattern recognition. Recently, machine learning (ML) has been also proposed as an alternative technique in health classification. In this work, the predictive accuracy of statistical v. ML methodologies as regards the association of dietary patterns on CVD risk was tested. During 2001-2002, 3042 men and women (45 (sd 14) years) were enrolled in the ATTICA study. In 2011-2012, the 10-year CVD follow-up was performed among 2020 participants. Item Response Theory was applied to create a metric of combined 10-year cardiometabolic risk, the 'Cardiometabolic Health Score', that incorporated incidence of CVD, diabetes, hypertension and hypercholesterolaemia. Factor analysis was performed to extract dietary patterns, on the basis of either foods or nutrients consumed; linear regression analysis was used to assess their association with the cardiometabolic score. Two ML techniques (k-nearest-neighbor's algorithm and random-forests decision tree) were applied to evaluate participants' health based on dietary information. Factor analysis revealed five and three factors from foods and nutrients, respectively, explaining 54 and 65 % of the total variation in intake. Nutrient and food pattern regression models showed similar accuracy in correctly classifying an individual according to the cardiometabolic risk (R 2=9.6 % and R 2=8.3 %, respectively). ML techniques were superior compared with linear regression in correct classification of the individuals according to the Health Score (accuracy approximately 38 v. 6 %, respectively), whereas the two ML methods showed equal classification ability. Conclusively, ML methods could be a valuable tool in the field of nutritional epidemiology, leading to more accurate disease-risk evaluation. PMID- 29789038 TI - Pain management practices surrounding lumbar punctures in children: A survey of Canadian emergency physicians. AB - CLINICIAN'S CAPSULE What is known about the topic? Few physicians adhere to recommendations surrounding analgesia for pediatric lumbar punctures (LPs). What did this study ask? How willing are emergency physicians to provide analgesia for pediatric LPs? What did this study find? Compared to older children, the willingness to provide analgesia was suboptimal in a young infant. Why does this study matter to clinicians? Knowledge translation should focus on dispelling misconceptions and emphasize the importance of analgesia for young infants undergoing LPs. PMID- 29789039 TI - Prospective association between adherence to dietary recommendations and incident depressive symptoms in the French NutriNet-Sante cohort. AB - A posteriori healthier dietary patterns and several nutrients have been associated with lower risks of depression in various studies; however, evidence is lacking with regard to the prospective association between adherence to nutritional recommendations (food-based and nutrient-based recommendations) and incident depression or depressive symptoms. In this study, we investigate such associations in the NutriNet Sante cohort. The study sample included 26 225 participants (aged 18-86 years) who were initially free of depressive symptoms. Adherence to nutritional recommendations was measured by four scores namely modified French Programme National Nutrition Sante-Guideline Score (mPNNS-GS), Alternative Healthy Eating Index-2010 (AHEI-2010), Probability of Adequate Nutrient Intake Dietary Score (PANDiet) and Diet Quality Index-International (DQI I), using non-consecutive dietary record data during the first 2 years of follow up (mean number of recording days=8, sd 2). Depressive symptoms were defined by a Center for Epidemiologic Studies Depression Scale (CES-D) score >=17 for men and >=23 for women. We used Cox proportional hazards models to estimate hazard ratios and 95 % CI, modelling the dietary scores as standardised continuous variables and as tertiles. Over a mean follow-up of 6 years, we identified 2166 incident cases of depressive symptoms. All dietary scores with the exception of the AHEI 2010 were significantly inversely associated with incident depressive symptoms. In the fully adjusted model, an increase of 1 sd in the mPNNS-GS, PANDiet and DQI I was, respectively, associated with an 8 % (95 % CI 4, 13), 5 % (95 % CI 1, 9) and 9 % (95 % CI 5, 13) reduction in the risk of depressive symptoms. Overall, these findings suggest that diet in accordance with national or international guidelines could have beneficial effects with regard to mental health. PMID- 29789040 TI - Adsorption and Oxidation of As(III) on Iron (Hydro)Oxides. AB - Iron (hydro)oxides, including poorly crystalline ferrihydrite and the more crystalline forms, hematite and magnetite, play an important role in the biogeochemical cycling of arsenic in aquatic environments. In this study, adsorption and oxidation experiments for As(III) were performed on ferrihydrite, hematite, and magnetite, respectively. The results showed that the three iron (hydro)oxides acted as a catalyst for the oxidation of As(III) in the presence of oxygen. The variation in the oxidation states of As(III) on iron (hydro)oxides were confirmed by X-ray Absorption Near-Edge Structure (XANES) spectra. Adsorption kinetics of As(III) followed a pseudo-second-order equation in the three iron (hydro)oxides systems. Oxidation of As(III) on the three iron (hydro)oxides was observed by the determination of total As(V) concentration. The pseudo-first-order equations satisfactorily described the oxidation kinetics data. The oxidation rate constants in the different iron (hydro)oxide systems followed the order: hematite > ferrihydrite > magnetite, that is, 0.0111, 0.0021, and 0.0009 h-1, respectively. PMID- 29789041 TI - Effect of Water Quality and Temperature on the Efficiency of Two Kinds of Hydrophilic Polymers in Soil. AB - In this study, evaluation of two-superabsorbent effects, Super-AB-A-300 and Super-AB-A-200 in a sandy soil on the water retention capability and saturated hydraulic conductivity (Ks) at different water quality and soil temperature were done. The Super-AB-A-200 was less effective in water uptake than Super-AB-A-300. The efficiency of these polymers in water retention was negatively influenced by the water quality and temperature. The efficiency of these polymer treatments in water uptake reduced significantly (P < 0.05) with increasing soil temperature. In the control soil, the Ks stayed nearly constant with increasing soil temperature. As compared to the untreated control, the treated soil demonstrated a significant (P < 0.05) linear increase of Ks with increasing soil temperature. In the control soil, the water holding properties curve did not change with increasing soil temperature. PMID- 29789042 TI - Phytoplankton Functional Groups Variation and Influencing Factors in a Shallow Temperate Lake. AB - The present study was carried out in Luoma Lake, a shallow lake in temperate eastern China. Based on a two-year study, the dynamics of phytoplankton functional groups and influencing factors were analyzed. A total of 178 taxa were identified and sorted into 20 codons, according to the phytoplankton functional group classification. In order to find the environmental factors driving phytoplankton variations, fifteen groups were analyzed in detail using redundancy analysis. Groups P (Fragilaria crotonensis), X2 (Chlamydomonas globosa, C. microsphaera and Chroomonas acuta), and MP (Navicula rotaeana) were dominant during low temperature periods, whereas groups X2, S1 (Pseudanabaena limnetica), and W1 (Euglena sp.) were dominant during high temperature periods. Water temperature, total phosphorus, and ammonium were the significant driving factors explaining phytoplankton succession. Furthermore, total phosphorus and ammonium could be broadly used in risk management for potential algal blooms in Luoma Lake. PMID- 29789043 TI - Statistical Expose of a Multiple-Compartment Anaerobic Reactor Treating Domestic Wastewater. AB - Mainstream anaerobic treatment of domestic wastewater is a promising energy generating treatment strategy; however, such reactors operated in colder regions are not well characterized. Performance data from a pilot-scale, multiple compartment anaerobic reactor taken over 786 days were subjected to comprehensive statistical analyses. Results suggest that chemical oxygen demand (COD) was a poor proxy for organics in anaerobic systems as oxygen demand from dissolved inorganic material, dissolved methane, and colloidal material influence dissolved and particulate COD measurements. Additionally, univariate and functional boxplots were useful in visualizing variability in contaminant concentrations and identifying statistical outliers. Further, significantly different dissolved organic removal and methane production was observed between operational years, suggesting that anaerobic reactor systems may not achieve steady-state performance within one year. Last, modeling multiple-compartment reactor systems will require data collected over at least two years to capture seasonal variations of the major anaerobic microbial functions occurring within each reactor compartment. PMID- 29789044 TI - Shifting Paradigms in Caring for Older Adults. PMID- 29789045 TI - Getting Paid for Clinical Services. AB - Increasingly, pharmacists are providing advanced, patient-centered clinical services. However, pharmacists are not currently included in key sections of the Social Security Act, which determines eligibility to bill and be reimbursed by Medicare. Many state and private health plans also cite the omission from Medicare as the rationale for excluding reimbursement of pharmacists for clinical services. This has prompted forward-thinking pharmacists to seek opportunities for reimbursement in other ways, allowing them to provide value to the health care system, while carving out unique niches for pharmacists to care for patients. PMID- 29789046 TI - Management of Venous Thromboembolism in the Elderly: A Review of the Non-Vitamin K Oral Anticoagulants. AB - Objective To provide an up-to-date review of the available evidence regarding pharmacotherapeutic management of venous thromboembolic events in the geriatric population. Data Sources A PubMed search of articles published through August 2017 was performed using a combination of the following words: apixaban, betrixaban, dabigatran, edoxaban, enoxaparin, geriatric, heparin, idaricizumab, rivaroxaban, and venous thromboembolism. Study Selection/data Extraction Relevant original research, review articles, and guidelines were assessed for the management of elderly patients with venous thromboembolism (VTE). References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results. Data Synthesis VTE, which includes deep vein thrombosis and pulmonary embolism, is common in the geriatric population. Elderly patients are at high risk for VTE, but management is complicated by comorbidities and a higher risk of bleeding. Until recently, warfarin has been the mainstay of therapy. Newer oral anticoagulants, which include apixaban, dabigatran, edoxaban, and rivaroxaban are now available, but there is limited information on their safety and efficacy in the geriatric population. This article reviews the current literature regarding outcomes and summarizes pharmacotherapeutic management of VTE in the elderly population. Conclusion Appropriate management of pharmacotherapy for VTE can help improve outcomes in elderly patients, and pharmacists can provide guidance and education regarding evidence-based therapy. PMID- 29789047 TI - Concerns for Bleeding in the Elderly with the Use of Direct Oral Anticoagulants. AB - Since Food and Drug Administration approval of dabigatran in 2010, direct oral anticoagulants (DOACs) have been alternatives to warfarin for patients who are at risk for cardioembolic complications of nonvalvular atrial fibrillation. Unfortunately, there are limited safety data available on the use of these newer agents in older adults, particularly risks of gastrointestinal, intracranial, and major bleeding (as defined by the International Society on Thrombosis and Haemostasis) in those 75 years of age and older. The purpose of this manuscript is to provide a review of available literature regarding the risk of bleeding in older adults for each DOAC based on available retrospective cohort, secondary, and subgroup analyses, and to highlight the need for additional safety information in this population. PMID- 29789048 TI - Pharmacist Impact on Tacrolimus Serum Concentrations in Liver Transplant Patients. AB - Objective The purpose of this quality-improvement project was to determine if a pharmacist consultation following a liver transplant is associated with an increased percentage of drug levels in range after the patient sees the pharmacist. Setting Tertiary care, multispecialty medical clinic, and hospital providing solid-organ transplant. Practice Description Pharmacist consult service in a tertiary care, multispecialty medical clinic and hospital providing solid organ transplant. Practice InnovationProvision of liver post-transplant consultations, not required by the Centers for Medicare & Medicaid Services, that results in therapeutic drug level improvement. Main Outcome MeasureTacrolimus therapeutic drug levels in range. Results A 96% improvement in quantity of therapeutic tacrolimus levels was seen in liver post-transplant patients after pharmacist post-transplant consultation. Results revealed 59 out of 74 (79.7%) post-liver transplant patients, 25 to 77 years of age (average 59.7 years), had an increased number of therapeutic tacrolimus levels after pharmacist post transplant consultation. ConclusionWithout a pharmacist consultation following a liver transplant, patients may have a higher number of tacrolimus levels out of therapeutic range, placing them at increased risk for possible graft loss from low tacrolimus levels or toxicity resulting from high tacrolimus levels. Improvement in therapeutic tacrolimus levels after liver transplant was observed after patients received consultation and education from a clinical pharmacist. This finding creates an opportunity for pharmacists to implement services for patients after liver transplants to improve therapeutic tacrolimus levels. PMID- 29789050 TI - Long-Term Care: The Thorniest Health Care Problem. PMID- 29789051 TI - Nurses Inspire, Innovate, and Influence. PMID- 29789049 TI - The Impact of Cholinesterase Inhibitors with or without Memantine on Antipsychotic Prescribing. AB - Background Alzheimer's disease (AD) medications have been suggested to positively affect behavior, though not universally in all studies. Their impact on antipsychotic use is not well-defined. Methods This cross-sectional, retrospective study evaluated residents with AD on cholinesterase inhibitors, memantine, both, or neither throughout multiple long-term care facilities during July 2014. Patients were included if they: were between 65 and 89 years of age, had a diagnosis of AD, and had a cognitive assessment within three months of the study period. Patients residing in the facility for 100 days or fewer, or those having a Centers for Medicare & Medicaid Services-approved diagnosis for antipsychotic use were excluded. The primary outcome was the prevalence of antipsychotic prescribing in patients receiving AD medications compared with those without AD therapy. The Texas Tech University Health Sciences Center institutional review board approved the study protocol. Results Of 1,282 patients screened, 285 (161 AD medications and 124 no-AD medications) were analyzed. Median cognitive status scores suggested severe cognitive impairment. Patients receiving AD medications had higher antipsychotic utilization compared with those without AD medications (27% vs. 19%, respectively; P = 0.08). Patients receiving combination AD medications had the highest antipsychotic use. No statistically significant differences were detected in cognitive status subgroups. Of interest is that a post-hoc analysis found a statistically significant association with greater antipsychotic use and increasing number of AD medications. Conclusion Long-term care facility residents with AD receiving AD medications had higher rates of antipsychotic use compared with those not receiving AD treatment. The link between antipsychotic use and the number of AD medications may point to overprescribing in dementia with behavioral disturbances as a potential contributing factor. PMID- 29789052 TI - Congenital Bilateral Eyelid Eversion and Chemosis: A Case Study. AB - This case reports the findings and management of a late preterm female infant born with congenital bilateral eyelid eversion with chemosis. The pathogenic process remains unknown but typically presents at birth, predominantly affecting the upper eyelid of both eyes. Black males, patients with trisomy 21, and collodion infants have a higher incidence of eyelid eversion. Treatment modalities range from conservative therapy including eye patching with antibiotic and lubricating ointment to invasive surgical eyelid suturing. In this case report, successful resolution of chemosis and eyelid inversion occurred with conservative management. PMID- 29789053 TI - Management of Meconium-Stained Newborns in the Delivery Room. AB - The approach to the management of meconium-stained newborns in the delivery room has been changing for over 40 years. The goal is to prevent meconium aspiration syndrome (MAS) and complications related to MAS. For decades, airway obstruction was believed to be a major component of MAS and, consequently, suction maneuvers to remove meconium from the airways were recommended to decrease the frequency and severity of MAS. Initial recommendations were based on observational studies. However, the incidence of MAS and mortality related to MAS has declined since the 1970s, mostly because of a decrease in the number of postterm deliveries. Recently updated guidelines by the American Heart Association and the Neonatal Resuscitation Program have reflected the strength of evidence supporting tracheal intubation and suctioning for nonvigorous, meconium-stained newborns. This article examines practice change since the 1970s in the delivery room management of meconium-stained newborns and evaluates evidence behind the changes. PMID- 29789054 TI - Applying Developmentally Supportive Principles to Diapering in the NICU: What We Know. AB - Developmental care measures are integrated in the NICU, but these measures are largely overlooked when it comes to standard care activities such as diapering. This general review of developmental care in the NICU discusses how caregivers can apply appropriate, individualized developmental care measures to diapering regimens. Numerous opportunities to expand developmental care measures into diapering care are identified; these opportunities can protect and promote sleep for hospitalized infants, enhance the diapering environment, minimize stress that infants may experience with diapering, improve infant skin health outcomes through use of evidence-based skin care practices, and foster family involvement during diapering care in the NICU. A developmental approach to diapering offers hospitalized infants regular opportunities to reach their neurodevelopmental potential. PMID- 29789056 TI - The Six-Hour Window: How the Community Hospital Nursery Can Optimize Outcomes of the Infant with Suspected Hypoxic-Ischemic Encephalopathy. AB - Perinatal hypoxia is a devastating event before, during, or immediately after birth that deprives an infant's vital organs of oxygen. This injury at birth often requires a complex resuscitation and increases the newborn's risk of hypoxic-ischemic encephalopathy (HIE). The resuscitation team in a community hospital nursery may have less experience with complex resuscitation and post resuscitation care of this infant than a NICU. This article provides the neonatal nurse in a Level I or Level II nursery with information about resuscitation and post-resuscitation care of an infant at risk of HIE while awaiting transport to a NICU for therapeutic cooling. The article describes the infant at risk for HIE, discusses pathophysiology and treatment of HIE, and lists essential components of post-resuscitation care while awaiting transport to an NICU, the importance of communication with the receiving NICU, and strategies for supporting the family. PMID- 29789057 TI - Case Study: Cystic Fibrosis in the Newborn. AB - Cystic fibrosis (CF) is considered one of the most commonly occurring fatal genetic disorders. This disorder is associated with pancreatic insufficiency and pulmonary complications. However, at birth the initial complications are associated with bowel obstruction. Cystic fibrosis management warrants an interdisciplinary team because this disorder affects various organ systems. Effective management of the newborn with CF assists in improving the child's overall prognosis. Family support is critical throughout the prenatal and postnatal periods. The case presented reviews a child born with suspected CF and the clinical course within the NICU. PMID- 29789058 TI - Prevention and Treatment of Respiratory Distress Syndrome in Preterm Neonates. AB - Respiratory distress syndrome (RDS) impacts a high proportion of preterm neonates, resulting in significant morbidity and mortality. Advances in pharmacotherapy, specifically antenatal corticosteroids and postnatal surfactant therapy, have significantly reduced the incidence and impact of neonatal RDS. Antenatal corticosteroids accelerate fetal lung maturation by increasing the activity of enzymes responsible for surfactant biosynthesis, resulting in improved lung compliance. Maternal antenatal corticosteroid treatment has improved survival of preterm neonates and lowered the incidence of brain injury. After birth, exogenous surfactant administration improves lung compliance and oxygenation, resulting in reductions in the incidence of pneumothorax and of death. Future research will identify the optimal surfactant product, timing of the initial dose, and mode of delivery. PMID- 29789061 TI - News of the Academy of Neonatal Nursing. PMID- 29789060 TI - Continuing Education Course. PMID- 29789059 TI - When a Baby Is Sent Away: Evidence to Support Best Practice After Neonatal Transport. AB - Every day neonates are transported from the birth hospital to a tertiary neonatal care center. Separation of mother and neonate in the hours immediately following birth interrupts the bonding process and can have long-term implications for the mother-child relationship. This article synthesizes the literature focused on mothers' experiences with a neonate being transported to a tertiary NICU and identifies evidence-based practices specific to these situations. PMID- 29789062 TI - Editorial. PMID- 29789063 TI - NanoElectrocatalysis: From Basic Research to Applications in Energy Conversion. AB - In this article an overview of our research in the field of nanoelectrocatalysis, in particular electrocatalytic energy conversion, is presented. Our research comprises the areas of catalyst preparation as well as performance evaluation of model and applied electrocatalysts with respect to activity, selectivity, and stability. Our aim is to understand the fundamental properties that determine the performance of electrocatalysts for particular processes and to build a bridge between fundamental research and realistic applications. In our research we prepare catalyst materials, study the interface between the catalyst and the electrochemical environment, i.e. the solid-liquid interface, and perform kinetic measurements. Furthermore, such research relies to a large extent on material characterization techniques as well as the development and application of advanced experimental setups. PMID- 29789064 TI - Surface and Defect Chemistry of Oxide Materials. AB - Oxides and oxide-derived materials find ubiquitous applications in many industrial applications. These materials usually contain point defects, the concentration and type depending on the synthesis and operating conditions. Many of the functional properties are determined or strongly affected by the presence of these point defects. Despite steady advances in experimental techniques it is still difficult to unambiguously identify point defects and resulting atomic scale mechanisms from experiment alone. Atomic-scale computational approaches such as density functional theory (DFT) provide an alternative approach that ideally complements experimental investigations. The resulting fundamental understanding of defect-induced mechanisms combined with the knowledge of how to tailor a point-defect profile to induce new functionality opens exciting new avenues to engineer novel material properties. This account discusses some case studies of defect-induced functionality in the area of oxide electronics and photocatalysis, giving a general flavour of our current understanding of the role of defects in these applications. PMID- 29789066 TI - Exploring Modular Glycolipids Involved in Nematode Chemical Communication. AB - Chemical communication in nematodes has been known for over half a century, but the underlying molecular basis remained largely elusive. Recent advances in analytical techniques facilitated the characterization of a modular glycolipid library based on the dideoxysugar L-ascarylose, which modulates behavior and development in the model organism C. elegans. Ascaroside signaling is highly conserved in nematodes and represents a key factor in nematode chemical ecology. Ascaroside biosynthesis depends on the co-option of the peroxisomal beta oxidation cycle and in addition integrates a large diversity of additional building blocks derived from various primary metabolic pathways to give rise to species-specific modular assemblies, thus, transcending the concept of strictly segregated primary versus secondary metabolism. PMID- 29789065 TI - Towards a Synthetic Mitochondrion. AB - Our group at the University of Bern uses biochemical and biophysical techniques to unravel details of the molecular mechanism of membrane proteins. Of special interest are the large multi-subunit complexes of the universally conserved respiratory chain and the ATP synthase that are found in mitochondria and aerobic bacteria. In a bottom-up approach using purified membrane proteins and synthetic lipids, we aim to mimic the basic processes of oxidative phosphorylation. We further develop methodologies to increase the complexity of such artificial systems, paving the way for a synthetic mitochondrion. In this minireview, we summarize recent efforts of our groups and others towards a synthetic respiratory chain. PMID- 29789067 TI - Engineering Aspects of Protein Interactions and Self-assembly. AB - In the new Laboratory for Biochemical Engineering (LBCE) at ETH Zurich researchers combine principles of chemical engineering with microfluidic technology and biophysical methods to investigate the physical determinants of biomolecular self-assembly in living organisms. In this account, we show the impact of this activity on concrete applications in biomedical sciences and biotechnology. We focus in particular on the field of protein aggregation and phase separation, and we highlight examples in the context of diagnosis and treatment of Alzheimer's disease and neurodegenerative disorders, cell compartmentalization as well as manufacturing and delivery of therapeutic proteins. PMID- 29789068 TI - Understanding Chemical Reactions beyond Transition-State Theory. AB - Transition-state theory is one of the most successful theories in chemistry. Not only does it provide a simple formula for computing the rate of a reaction but it defines our understanding of how a chemical reaction occurs - by overcoming an energy barrier. However, the theory is based on classical assumptions and ignores several quantum effects which can be important for certain reactions, particularly those involving hydrogen transfer at low temperatures. We are developing a more general quantum version of transition-state theory which reveals how quantum tunnelling and nonadiabatic effects can strongly affect the rate. PMID- 29789069 TI - Towards the Ultimate Membranes: Two-dimensional Nanoporous Materials and Films. AB - The energy-efficient separation of molecules has been a popular topic in chemistry and chemical engineering as a consequence of the large energy-footprint of separation processes in the chemical industry. The Laboratory of Advanced Separations (LAS) at EPFL, led by Prof. Kumar Varoon Agrawal, is focused to develop next-generation, high-performance membranes that can improve the energy efficiency of hydrogen purification, carbon capture, hydrocarbon and water purification. For this, LAS is seeking to develop the ultimate nanoporous membranes, those with a thickness of 1 nm and possessing an array of size selective nanopores. In this article, the research activities at LAS, especially in the bottom-up and top-down synthesis of chemically and thermally stable, nanoporous two-dimensional materials and membranes are discussed. PMID- 29789070 TI - The Three C's of Cethrene. AB - Molecules that contain one or more unpaired electrons delocalized within a pi conjugated backbone are promising candidates for applications in spin electronics or simply 'spintronics'. Our group develops functional organic materials based on pi-conjugated hydrocarbon molecules, where the electrons are unpaired either in the ground state or in the excited state that is low in energy and can be populated thermally. We aim to learn how to introduce and control a multitude of properties, namely, optical, chiroptical, magnetic, and conductive, in a bulk material made of these molecules, by manipulating spin interactions between the unpaired electrons. The first model system that was developed in our group is a hydrocarbon named cethrene, which has a diradicaloid singlet ground state and a low-lying triplet excited state. In this article, the structural parameters and their impact on the properties and reactivity of cethrene are discussed within the realm of the three C's that symbolize cethrene's C-shape, chirality, and chameleonic reactivity. PMID- 29789071 TI - Dynamic ab initio Methods for Vibrational Spectroscopy. AB - Our group focuses on the development of computational methods derived from quantum mechanics and their application to a variety of challenging systems ranging from (bio-)molecules over coordination compounds to solar light-driven processes. In this review, we describe our recent activities for accurate calculation of spectroscopic properties. Emphasis is put on forefront methods for vibrational spectroscopy, in particular with respect to condensed phase systems, based on ab initio molecular dynamics. This approach has several advantages compared to standard static approaches and proven to be a highly valuable tool for in-depth analysis of complex systems. PMID- 29789072 TI - New Earth-abundant Materials for Large-scale Solar Fuels Generation. AB - The solar resource is immense, but the power density of light striking the Earth's surface is relatively dilute, necessitating large area solar conversion devices in order to harvest substantial amounts of power for renewable energy applications. In addition, energy storage is a key challenge for intermittent renewable resources such as solar and wind, which adds significant cost to these energies. As the majority of humanity's present-day energy consumption is based on fuels, an ideal solution is to generate renewable fuels from abundant resources such as sunlight and water. In this account, we detail our recent work towards generating highly efficient and stable Earth-abundant semiconducting materials for solar water splitting to generate renewable hydrogen fuel. PMID- 29789076 TI - SimplyNano-Experimentierkoffer und die Plattform Swiss Nano-Cube. AB - Die Experimentierkoffer SimplyNano 1 und 2 wurden von der Innovationsgesellschaft mbH entwickelt und von der SimplyScience Stiftung herausgegeben. Sie enthalten Unterrichtsunterlagen fur die Erklarung und Vorstellung einfacher Phanomene der Nanotechnologie. Es stehen Schuleranleitungen, Kommentare fur Lehrpersonen und Vortragsfolien zur Verfugung. Weiterfuhrende Unterlagen und Ideen zu Nanotechnologie im Unterricht bietet die Plattform Swiss Nano-Cube. PMID- 29789077 TI - Open Science in Switzerland. AB - The results of research financed by public funds are regarded as a public good and should be published electronically so that they are immediately and publicly available without charge and can be reused by third parties. The SNSF supports the principle of free accessibility: it has adopted the aim that all publications resulting from its funding will be openly accessible as of 2020. The article is a summary of information provided by the SNSF More information are available on the SNSF website. PMID- 29789079 TI - CHIMIA Report/Company News. PMID- 29789078 TI - Surface Immobilization and Shielding of a Transaminase Enzyme for the Stereoselective Synthesis of Pharmaceutically Relevant Building Blocks. AB - Transaminases are enzymes capable of stereoselective reductive amination; they are of great interest in the production of chiral building blocks. However, the use of this class of enzymes in industrial processes is often hindered by their limited stability under operational conditions. Herein, we demonstrate that a transaminase enzyme from Aspergillus terreus can be immobilized at the surface of silica nanoparticles and protected in an organosilica shell of controlled thickness. The so-protected enzyme displays a high biocatalytic activity, and additionally provides the possibility to be retained in a reactor system for continuous operation and to be recycled. PMID- 29789081 TI - The Need for Global Connection and Collaboration. PMID- 29789082 TI - The Differential Effect of Sustained Operations on Psychomotor Skills of Helicopter Pilots. AB - INTRODUCTION: Flying a helicopter is a complex psychomotor skill requiring constant control inputs from pilots. A deterioration in psychomotor performance of a helicopter pilot may be detrimental to operational safety. The aim of this study was to test the hypothesis that psychomotor performance deteriorates over time during sustained operations and that the effect is more pronounced in the feet than the hands. The subjects were helicopter pilots conducting sustained multicrew offshore flight operations in a demanding environment. The remote flight operations involved constant workload in hot environmental conditions with complex operational tasking. METHODS: Over a period of 6 d 10 helicopter pilots were tested. At the completion of daily flying duties, a helicopter-specific screen-based compensatory tracking task measuring tracking accuracy (over a 5-min period) tested both hands and feet. Data were compared over time and tested for statistical significance for both deterioration and differential effect. RESULTS: A statistically significant deterioration of psychomotor performance was evident in the pilots over time for both hands and feet. There was also a statistically significant differential effect between the hands and the feet in terms of tracking accuracy. The hands recorded a 22.6% decrease in tracking accuracy, while the feet recorded a 39.9% decrease in tracking accuracy. DISCUSSION: The differential effect may be due to prioritization of limb movement by the motor cortex due to factors such as workload-induced cognitive fatigue. This may result in a greater reduction in performance in the feet than the hands, posing a significant risk to operational safety.McMahon TW, Newman DG. The differential effect of sustained operations on psychomotor skills of helicopter pilots. Aerosp Med Hum Perform. 2018; 89(6):496-502. PMID- 29789083 TI - Low Baseline Sympathetic Tone Correlates to a Greater Blood Pressure Change in the Cold Pressor Test. AB - BACKGROUND: The cold pressor test (CPT) involves acute hand or foot exposure to cold water. CPT hyper-responders have unique traits, including risk of hypertension and a greater vasoconstrictor reserve and g force tolerance compared to hypo-responders. The purpose of this study was to uncover differences in cardiovascular and sympathetic biomarkers between responder types. METHODS: Healthy volunteers (N = 30) submerged one hand into cold water (3.3 +/- 0.8 degrees C) for 5 min. Blood pressure, heart rate, cardiac output, and cardiac parameters were recorded using an automated monitor, impedance cardiography, and a beat-to-beat monitoring system. We analyzed for salivary alpha-amylase (SalphaA), which is a convenient biomarker of the sympathetic nervous system. Subjects were stratified post hoc into hyper-responders (>= 22 mmHg) and hypo responders (< 22 mmHg) based on change in systolic blood pressure during CPT. RESULTS: Hyper-responders had a significantly lower baseline heart rate (64 +/- 7 bpm), cardiac output (5.6 +/- 0.9 L . min-1), and SalphaA (60 +/- 37 U . mL-1) compared to hypo-responders (73 +/- 9 bpm, 6.9 +/- 1.3 L . min-1, 165 +/- 122 U . mL-1). During the cold immersion, hyper-responders had significantly higher systolic blood pressure (150 +/- 14 mmHg), diastolic blood pressure (91 +/- 10 mmHg), mean arterial pressure (129 +/- 17 mmHg), and systemic vascular resistance (1780 +/- 640 dyn . s-1 . cm-5) than hypo-responders (130 +/- 14 mmHg, 81 +/- 10 mmHg, 110 +/- 9 mmHg, 1290 +/- 220 dyn . s-1 . cm-5). The change in systolic blood pressure correlated with baseline SalphaA (r = -0.455, P = 0.011) and baseline heart rate (r = -0.374, P = 0.042). DISCUSSION: Baseline characteristics influenced by sympathetic tone such as SalphaA, heart rate, and cardiac output are indicative of responses to CPT. Our data supports the use of baseline values to predict blood pressure response to acute cold exposure and indicates an intrinsic difference between CPT responder phenotypes.Youssef M, Ghassemi A, Carvajal Gonczi CM, Kugathasan TA, Kilgour RD, Darlington PJ. Low baseline sympathetic tone correlates to a greater blood pressure change in the cold pressor test. Aerosp Med Hum Perform. 2018; 89(6):503-509. PMID- 29789084 TI - Amplified Pilot Head Vibration and the Effects of Vibration Mitigation on Neck Muscle Strain. AB - INTRODUCTION: Rotary wing pilot neck strain is increasing in prevalence due to the combined effects of head supported mass (e.g., Night Vision Goggles, head mounted displays) and whole-body vibration. This study examined the physiological responses of pilots during exposure to whole-body vibration (WBV) representative of the National Research Council's Bell 412 helicopter in forward flight. WBV levels were measured and evaluated using the ISO-2631-1-1997 WBV standards. METHODS: Twelve pilots (aged 20-59 yr, 7 of the 12 with 20+ years flight experience) underwent six 15-min vibration trials on a human rated shaker platform. Participants were exposed to three vibration levels (-25%, normal, and +25% amplitude; Levels 1-3, respectively) while seated on an Original Equipment Manufacturer (OEM) or vibration mitigating (MIT) cushion. Upper back and neck electromyography (EMG) and acceleration were continuously recorded. RESULTS: Normalized EMG amplitude was higher using the OEM compared to the MIT during Level 2 (0.18 vs. -0.27) and Level 3 (0.24 vs. -0.14) for the anterior neck muscles. Health weighted vibration amplitude at the head (Mean of 3 levels: OEM = 1.19 and MIT = 1.11 m . s-2) was larger than the vibration amplitude at the seat (Mean of 3 levels: OEM = 0.77 and MIT = 0.70 m . s-2). DISCUSSION: The amplification of head vibration relative to the seat, and the significant effects of vibration level, as well as the vibration mitigation cushion, on neck EMG amplitude support the need for revisions to the ISO-2631-1 standard to account for the head and neck response to whole-body vibration.Wright Beatty HE, Law AJ, Thomas JR, Wickramasinghe V. Amplified pilot head vibration and the effects of vibration mitigation on neck muscle strain. Aerosp Med Hum Perform. 2018; 89(6):510-519. PMID- 29789085 TI - Acute Exposure to Low-to-Moderate Carbon Dioxide Levels and Submariner Decision Making. AB - BACKGROUND: Submarines routinely operate with higher levels of ambient carbon dioxide (CO2) (i.e., 2000 - 5000 ppm) than what is typically considered normal (i.e., 400 - 600 ppm). Although significant cognitive impairments are rarely reported at these elevated CO2 levels, recent studies using the Strategic Management Simulation (SMS) test have found impairments in decision-making performance during acute CO2 exposure at levels as low as 1000 ppm. This is a potential concern for submarine operations, as personnel regularly make mission critical decisions that affect the safety and efficiency of the vessel and its crew while exposed to similar levels of CO2. The objective of this study was to determine if submariner decision-making performance is impacted by acute exposure to levels of CO2 routinely present in the submarine atmosphere during sea patrols. METHODS: Using a subject-blinded balanced design, 36 submarine-qualified sailors were randomly assigned to receive 1 of 3 CO2 exposure conditions (600, 2500, or 15,000 ppm). After a 45-min atmospheric acclimation period, participants completed an 80-min computer-administered SMS test as a measure of decision making. RESULTS: There were no significant differences for any of the nine SMS measures of decision making between the CO2 exposure conditions. DISCUSSION: In contrast to recent research demonstrating cognitive deficits on the SMS test in students and professional-grade office workers, we were unable to replicate this effect in a submariner population-even with acute CO2 exposures more than an order of magnitude greater than those used in previous studies that demonstrated such effects.Rodeheffer CD, Chabal S, Clarke JM, Fothergill DM. Acute exposure to low-to-moderate carbon dioxide levels and submariner decision making. Aerosp Med Hum Perform. 2018; 89(6):520-525. PMID- 29789086 TI - Acute Mild Hypoxic Hypoxia Effects on Cognitive and Simulated Aircraft Pilot Performance. AB - BACKGROUND: The effects of acute mild hypoxic hypoxia (HH) and physical activity on physiological measures, signs and symptoms, mood, fatigue, cognition, and performance on a simulated flight task were investigated between 8000 (8K; 2438 m) and 14,000 ft (14K; 4267 m). METHOD: In a hypobaric chamber, 16 military helicopter pilots were randomly exposed to 4 altitudes and 3 physical exertion levels. After each exercise period, participants identified targets on a designated flight path on a desktop simulator and completed a cognitive test battery. Cerebral regional and finger pulse oxyhemoglobin saturation levels (rSO2 and Spo2), heart and respiration rates were continuously monitored. Participants indicated their symptoms, mood and fatigue. RESULTS: rSO2 and Spo2 were affected by the increase of altitude and exercise level. Target identification accuracy and latency within the simulated flight task showed decrements at 8K, 10K (3048 m), 12K (3658 m), and 14K. Cognitive performance was degraded at 14K. More than 60% of the participants at 8K and 10K and more than 80% at 12K and 14K reported symptoms. Altitude increased symptoms, negative mood, general fatigue, and physical fatigue. DISCUSSION: Our findings indicate a significant influence of mild HH on a number of outcome measures at altitudes above 10K, where operational restrictions are well established. In contrast, there was no clear influence of HH on performance at lower altitudes (i.e., 8K and 10K). The occurrence of HH symptoms and the decrements in target identification latency and accuracy at 8K and 10K may negatively impact flight performance and require further study.Bouak F, Vartanian O, Hofer K, Cheung B. Acute mild hypoxic hypoxia effects on cognitive and simulated aircraft pilot performance. Aerosp Med Hum Perform. 2018; 89(6):526-535. PMID- 29789087 TI - Individual Differences in Adaptability to Isolated, Confined, and Extreme Environments. AB - INTRODUCTION: Future deep space missions will expose astronauts to more intense stressors than previously encountered. Isolation will be greater and more prolonged, living and work areas more confined, and communications and resupply channels to Earth longer and less reliable. Astronauts will need to function more autonomously, with less guidance and support from Earth. Thus, it is important to select and train astronauts who can adapt and function effectively under extreme and variable conditions. In order to identify factors linked to individual adaptability, we conducted a systematic review of the literature on cognitive and behavioral adaptation to isolated, confined, and extreme (ICE) environments. METHODS: We searched PubMed, Embase, Web of Science, and PsychINFO databases for studies addressing individual adaptability to ICE environments. Studies were rated for quality and fidelity to long-duration space missions and key results extracted. RESULTS: There were 73 studies that met all inclusion criteria. Adaptability attributes for ICE environments include intelligence, emotional stability, self-control, openness, achievement facets of conscientiousness, optimism, mastery, introversion, hardiness, task-oriented coping, past experience, low need for social support, and adequate sleep. DISCUSSION: This review identifies individual factors linked to adaptability under ICE conditions. Further studies are needed to verify causal directions and determine the relative importance of these factors.Bartone PT, Krueger GP, Bartone JV. Individual differences in adaptability to isolated, confined, and extreme environments. Aerosp Med Hum Perform. 2018; 89(6):536-546. PMID- 29789088 TI - The Danger Zone for Noise Hazards Around the Black Hawk Helicopter. AB - BACKGROUND: During ground operations, rotary-wing aircraft engines and subsystems produce noise hazards that place airfield personnel at risk for hearing damage. The noise exposure levels outside the aircraft during various operating conditions, and the distances from aircraft at which they drop to safe levels, are not readily available. The current study measured noise levels at various positions around the UH-60 Black Hawk helicopter for three operating conditions typically used when the aircraft is on the ground. METHODS: Microphones were positioned systematically around the helicopter and A-weighted sound pressure levels (SPLs) were computed from the recordings. In addition, the 85-dBA SPL contour around the aircraft was mapped. The resulting A-weighted SPLs and contour mapping were used to determine the noise hazard area around the helicopter. RESULTS: Measurements reported here show noise levels of 105 dB or greater in all operating conditions. The fueling location at the left rear of the aircraft near the auxiliary power unit (APU) is the area of greatest risk for noise-induced hearing loss (NIHL). Additionally, sound field contours indicate noise hazard areas (>85 dBA SPL) can extend beyond 100 ft from the helicopter. CONCLUSIONS: This report details the areas of greatest risk for auditory injury around the UH 60 Black Hawk helicopter. Our findings suggest the area of hazardous noise levels around the aircraft can extend to neighboring aircraft, particularly on the side of the aircraft where the APU is located. Hearing protection should be worn whenever the aircraft is operating, even if working at a distance.Jones HG, Greene NT, Chen MR, Azcona CM, Archer BJ, Reeves ER. The danger zone for noise hazards around the Black Hawk helicopter. Aerosp Med Hum Perform. 2018; 89(6):547 551. PMID- 29789089 TI - +Gz Exposure and Spinal Injury-Induced Flight Duty Limitations. AB - BACKGROUND: The present study aimed to find out if possible differences in early military flight career +Gz exposure level could predict permanent flight duty limitations (FDL) due to spinal disorders during a pilot's career. METHODS: The study population consisted of 23 pilots flying with Gz limitation (max limitation ranging from +2 Gz to +5 Gz) due to spinal disorders and 50 experienced (+1000 flight hours) symptomless controls flying actively in operative missions in the Finnish Air Force. Data obtained for all subjects included the level of cumulative Gz exposure measured sortie by sortie with fatigue index (FI) recordings and flight hours during the first 5 yr of the pilot's career. RESULTS: The mean (+/- SD) accumulation of FI in the first 5 yr of flying high-performance aircraft was 8.0 +/- 1.8 among the pilots in the FDL group and 7.7 +/- 1.7 in the non-FDL group. There was no association between flight duty limitations and early career cumulative +Gz exposure level measured with FI or flight hours. DISCUSSION: According to the present findings, it seems that the amount of cumulative +Gz exposure during the first 5 yr of a military pilot's career is not an individual risk factor for spinal disorders leading to flight duty limitation. Future studies conducted with FI recordings should be addressed to reveal the relationship between the actual level of +Gz exposure and spinal disorders, with a longer follow-up period and larger sample sizes.Honkanen T, Sovelius R, Mantysaari M, Kyrolainen H, Avela J, Leino TK. +Gz exposure and spinal injury induced flight duty limitations. Aerosp Med Hum Perform. 2018; 89(6):552-556. PMID- 29789090 TI - The Giant Hand Illusion Experienced on a Simulator. AB - BACKGROUND: This paper discusses a special kind of a sensory illusion-the Giant Hand illusion-that was experienced during an exercise on a flight simulator equipped with a VR headset. In the first part we describe spatial disorientation and the function of the vestibular apparatus during flight and its consequences. In this part, the sensory illusion simulator used for the experiment is mentioned. In the second part we describe the simulator and test flight. In the third part we discuss data retrieved during simulator flights that are important for explaining the Giant Hand illusion. CASE REPORT: A well-trained pilot experienced the Giant Hand illusion while executing instrument flight rules flight on a simulator. The Giant Hand illusion was detected from the simulation data and confirmed by the pilot afterward. DISCUSSION: The Giant Hand illusion is a rare type of sensory illusion. The pilot falsely evaluated the situation as a malfunction of the aircraft controls. If the pilot had not been informed by the operator that he might have been influenced by the illusion, he would probably have crashed the simulated aircraft. An unrecognized Giant Hand illusion during a flight can lead to fatal consequences. This case report shows the symptoms and data that can be used for early recognition of this type of illusion.Frantis P, Petru A. The Giant Hand illusion experienced on a simulator. Aerosp Med Hum Perform. 2018; 89(6):557-562. PMID- 29789091 TI - Spinal Stiffness in Prone and Upright Postures During 0-1.8 g Induced by Parabolic Flight. AB - INTRODUCTION: The purpose of this study was to analyze posterior-to-anterior spinal stiffness in Earth, hyper-, and microgravity conditions during both prone and upright postures. CASE REPORT: During parabolic flight, the spinal stiffness of the L3 vertebra of a healthy 37-yr-old man was measured in normal Earth gravity (1.0 g), hypergravity (1.8 g), and microgravity (0.0 g) conditions induced in the prone and upright positions. Differences in spinal stiffness were significant across all three gravity conditions in the prone and upright positions. Most effect sizes were large; however, in the upright posture, the effect size between Earth gravity and microgravity was medium. Significant differences in spinal stiffness between the prone and upright positions were found during Earth gravity and hypergravity conditions. No difference was found between the two postures during microgravity conditions. DISCUSSION: Based on repeated measurements of a single individual, our results showed detectable changes in posterior-to-anterior spinal stiffness. Spinal stiffness increased during microgravity and decreased during hypergravity conditions. In microgravity conditions, posture did not impact spinal stiffness. More data on spinal stiffness in variable gravitational conditions is needed to confirm these results.Swanenburg J, Meier ML, Langenfeld A, Schweinhardt P, Humphreys BK. Spinal stiffness in prone and upright postures during 0-1.8 g induced by parabolic flight. Aerosp Med Hum Perform. 2018; 89(6):563-567. PMID- 29789092 TI - Letter to the Editor re: You're the Flight Surgeon: Foot Drop: Response. PMID- 29789093 TI - Letter to the Editor re: You're the Flight Surgeon: Foot Drop: Letter. PMID- 29789094 TI - The Evolving Science of Drug Detection. PMID- 29789095 TI - You're the Flight Surgeon. AB - Holmes RL. You're the flight surgeon: zika virus infection. Aerosp Med Hum Perform. 2018; 89(6):572-575. PMID- 29789096 TI - Use of the Fieseler "Stork" in World War II Aeromedical Evacuation. PMID- 29789097 TI - This Month in Aerospace Medicine History. PMID- 29789098 TI - AsMA Constituent Organization Presidents for 2018-2019. PMID- 29789099 TI - Building capacity for change: evaluation of an organisation-wide leadership development program. AB - Objective. This study evaluated Leading 4 Change, a change leadership development program designed to support healthcare middle managers through a period of significant organisational change and enhance workplace resilience.Methods. A mixed methods evaluation was conducted within the program's framework of a quality improvement activity. Quantitative measures were participant responses (n=160) to online questionnaires, which were compared before and after the program, using an uncontrolled pre-post study design. Four questionnaires were used: Resilience @ Work, General Self-Efficacy, the 11-item Learning Organization Survey and organisational climate. Differences between the pre- and post-program periods were compared using linear mixed-effects models, incorporating repeated measures between 'pre' and 'post' periods. Qualitative data were obtained by interviewing four participants on three occasions during the program, and through text responses provided by participants during a presentation session after the program finished. Both interview data and textual data were subjected to thematic analysis.Results. Integration of data from quantitative and qualitative analyses generated three main findings: (1) participants were satisfied and engaged with the program, which met their learning objectives; (2) the program led to increased workplace resilience, in particular the ability to manage stress and self-efficacy for individuals; and (3) organisational learning perceptions were unchanged.Conclusion. Although conducted during a period of intense internal and external pressure, Leading 4 Change led to demonstrable effects. It effectively engaged middle managers across a health system. However, there was no evidence that the effect of the program extended beyond individual participants to their perceptions of their work environment as a learning organisation.What is known about the topic? Although much has been written about change management and change leadership within healthcare, the failure to manage the 'people' element and engage employees hampers the success of that change. However, how to engage employees and enhance their resilience and self-efficacy (self-belief to proactively manage) during change has been little explored. Further, the concept of a learning organisation has been developed in private, non-healthcare fields and there is little known about it in other areas, such as healthcare, particularly during change.What does this paper add? The paper describes the evaluation of a 16-week change leadership development program (Leading 4 Change) for middle managers of a public health system undergoing significant reform. It assesses how the program engaged employees, and how and to what extent their workplace resilience, self-efficacy and perceptions of their workplace as a learning organisation changed after the program. Based on the present study, individual development of staff does not necessarily translate directly to better staff perceptions of organisational outcomes.What are the implications for practitioners? Despite being clearly engaged with Leading 4 Change, quantitative and qualitative measures suggested mixed effects of the program on participants. Participants' self-rated workplace resilience, ability to manage stress and self efficacy increased after the program. However, there was no evidence that the effect of the program improved staff perceptions of their work as a learning organisation. For complex public sector healthcare organisations to become learning organisations, other organisational factors, in addition to staff development and training, require consideration. PMID- 29789100 TI - Healthcare resource utilisation by patients with coronary heart disease receiving a lifestyle-focused text message support program: an analysis from the TEXT ME study. AB - The 'Tobacco, Exercise and Diet Messages' (TEXT ME) study was a 6-month, single centre randomised clinical trial (RCT) that found a text message support program improved levels of cardiovascular risk factors in patients with coronary heart disease (CHD). The current analyses examined whether receipt of text messages influenced participants' engagement with conventional healthcare resources. The TEXT ME study database (N=710) was linked with routinely collected health department databases. Number of doctor consultations, investigations and cardiac medication prescriptions in the two study groups were compared. The most frequently accessed health service was consultations with a General Practitioner (mean 7.1, s.d. 5.4). The numbers of medical consultations, biochemical tests or cardiac-specific investigations were similar between the study groups. There was at least one prescription registered for statin, ACEI/ARBs and beta-blockers in 79, 66 and 50% of patients respectively, with similar refill rates in both the study groups. The study identified TEXT ME text messaging program did not increase use of Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) captured healthcare services. The observed benefits of TEXT ME reflect direct effects of intervention independent of conventional healthcare resource engagement. PMID- 29789101 TI - Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide. AB - PURPOSE: Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, possesses antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory properties. The aim of the present study was to investigate the effect of licofelone on lipopolysaccharide (LPS)-induced depression in a mouse model and also a possible role for nitric oxide (NO). METHODS: To elucidate the role of NO on this effect of licofelone (5 and 20 mg/kg, i.p.), L-NAME, a non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), a specific inducible NOS (iNOS) inhibitor; 7 nitroindazole (7-NI) a preferential neuronal NOS inhibitor (nNOS) and; L-arginine (L-Arg), as a NO donor, were used. The animal's behaviors were evaluated employing forced swimming test (FST), tail suspension test (TST) and open field test (OFT). RESULTS: LPS (0.83 mg/kg, i.p.) induced depressive-like behavior increasing immobility time in FST and TST. Conversely, licofelone (20 mg/kg i.p.) reversed the depressive effect of LPS and lowered the immobility time in FST and TST. On the other hand, pretreatment with L-Arg also reversed the antidepressant like effect of licofelone (20 mg/kg) in FST and TST. On the other hand, L-NAME (10 and 30 mg/kg), AG (50 and 100 mg/kg) and 7-NI (60 mg/kg) could potentiate licofelone (5 mg/kg) and lowered the immobility duration. CONCLUSIONS: NO down regulation possibly through iNOS and nNOS inhibition may involve in the antidepressant property of licofelone. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 29789103 TI - Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes. AB - PURPOSE: Adefovir is an antiviral drug that exhibits high hydrophilic properties and negligible bioavailability (less than 12%). It is only applied in the form of the ester prodrug adefovir dipivoxil (ADV). The oral bioavailability of ADV is limited (32% to 45%) by its low permeability (Class 3) and biological conversion of the prodrug to adefovir. Ion-pair formation is considered as an alternative approach to a covalent prodrug (ADV) to enhance intestinal permeation of adefovir. METHODS: The effect of various counter-ions (anionic, cationic and two quaternary ammonium salts) on the lipophilicity of adefovir was investigated by means of the n-octanol/buffer partitioning system, an in vitro transport model (PAMPA) and a biological membrane (everted gut sac). RESULTS: Quaternary ammonium salts, cetylpyridinium chloride (CPC) and cetrimide enhanced the lipophilicity of adefovir 136- and 87-fold, respectively. The apparent permeability of adefovir in combination with CPC (counter-ion) was 2.5-fold greater than ADV permeability in the PAMPA model. The apparent permeability of adefovir-CPC (counter-ion) was 1.3 fold greater than that of adefovir dipivoxil permeability in a biologic membrane (everted gut sac). CONCLUSION: These results suggest that the adefovir-CPC ion paired system has potential for improving the permeation of adefovir across the intestinal membrane. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 29789102 TI - An Update on Drug-induced Oral Reactions. AB - Adverse drug reactions (ADRs) are one of the major culprits in the development of oral lesions, which can be misdiagnosed with underlying diseases. The goal of this study is to summarize and update the current knowledge about drug-induced oral reactions. Electronic searches were performed in Scopus, Google Scholar, Cochrane and PubMed databases, for articles published between January 2008 and August 2017. Two authors screened the titles and abstracts for eligibility. Finally, 56 studies included in this review. There was no systematic homogeneity in the included studies; thereby no meta-analysis was performed. The most frequent oral ADR was xerostomia,andthe most reported cause was antihypertensive medications. Cardiovascular drugs were the most reported culprit agents for induction of oral ulcerative and vesiculo-bullous lesions, followed by methotrexate. Nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-blockers were found the most common responsible drugs for induction of oral lichen planus. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID- 29789104 TI - Functionalized Caprolactone-Polyethylene Glycol Based Thermo-Responsive Hydrogels of Silibinin for the Treatment of Malignant Melanoma. AB - PURPOSE: Silibinin, is a natural compound, which has shown anticancer activity in various malignancies. In this study, we evaluated the anticancer effects of silibinin in B16-F10 melanoma cells and developed a novel thermoresponsive hydrogel for local delivery of this compound. METHOD: A thermoresponsive hydrogel loaded with silibinin was prepared using triblock copolymers of poly[(alpha benzyl carboxylate-e-caprolactone)-co-(alpha-carboxyl-e-caprolactone)]ran-b-PEG-b [(alpha-benzyl carboxylate-e-caprolactone) -co-(alpha-carboxyl-e caprolactone)]ran (PCBCL-b-PEG-b-PCBCL), namely PolyGelTM, and compared with a Pluronic F-127 formulation of silibinin. Sol-gel transition temperature of hydrogels was measured by inverse flow method and modulated differential scanning calorimetry (MDSC). Silibinin loading efficiency was measured by HPLC. The MTT and clonogenic assays were used to assess the cytotoxicity and anti-proliferative effects of silibinin on B16-F10 melanoma cells. Flow cytotmetry was used to quantify the induced level of apoptosis and measure the intracellular level of activated STAT3 (pSTAT3) following silibinin treatment in B16.F10 cells. The effects of silibinin on the activation of oncogenic proteins were also evaluated by western blot. RESULTS: Silibinin inhibited cell proliferation (IC50 = 67 uM), provoked cell cycle arrest, induced apoptosis, suppressed key oncogenic pathways (i.e STAT3 and MEK/ERK), and enhanced the cytotoxic effects of doxorubicin in B16 F10 cells. Both PolyGelTM and Pluronic F-127 hydrogels were effective in loading silibinin. A lower drug release pattern within 24h, fitting first- order release kinetics, was observed for the release of silibinin from both gels compared to free drug. PolyGelTM demonstrated enhanced percutaneous absorption of silibinin through increasing mouse skin intracellular lipid fluidity as documented by DSC of skin following PolyGelTM use. Silibinin loaded in PolyGel TM inhibited the growth of B16-F10 cells (IC50 = 30 uM) and effectively suppressed pSTAT3 activity in B16-F10 cells at 10 uM. CONCLUSION: Our results imply a great potential for PolyGel TM formulations of silibinin for local treatment of malignant melanoma. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's content page. PMID- 29789106 TI - Pulmonary Bullae as an Indicator of an Elevated Risk of Renal Carcinoma. PMID- 29789107 TI - Disturbed Microcirculation as Cause. PMID- 29789105 TI - Oral Anticoagulation in Chronic Kidney Disease and Atrial Fibrillation. AB - BACKGROUND: Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. METHODS: This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. RESULTS: Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m2 should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m2), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus VKA are still debated. CONCLUSION: The cardiological societies' recommendation that patients with atrial fibrillation should be given oral anticoagulant drugs applies to the majority of such patients who also have chronic kidney disease. PMID- 29789108 TI - Occurence in Stages of Prediabetes. PMID- 29789109 TI - Supplemental Information Necessary. PMID- 29789110 TI - Amiodarone-Associated Vestibulopathy. PMID- 29789111 TI - Leprosy Neuritis. PMID- 29789112 TI - In Reply. PMID- 29789113 TI - A Fall From a Scaffold, an Ignited Smartphone, and a Burn on the Buttocks. PMID- 29789114 TI - Painful Oculomotor Nerve Palsy. PMID- 29789116 TI - 10th International Conference on managing fatigue: Managing fatigue to improve safety, wellness, and effectiveness. PMID- 29789115 TI - Hints on Diagnosing and Treating Headache. AB - BACKGROUND: Headache, like dizziness, is one of the more common presenting complaints in outpatient care and in the emergency room. More than 200 varieties of headache have been described, and the false impression may arise that the diagnosis and treatment of these syndromes is a highly challenging task. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed. RESULTS: In primary headache, the headache is not a symptom but a disease in its own right. There are four types of primary headache: migraine, tension headache, trigeminal autonomic cephalalgia, and other primary headache disorders. By definition, the physical examination is normal, including the neurological examination. Secondary headache, in contrast, is a symptom of another disease (e.g., a tumor or cerebral hemorrhage). Triptans and nonsteroidal anti inflammatory drugs (NSAID) are the drugs usually given for the acute treatment and prophylaxis of migraine. In tension headache, NSAID are given acutely, and tricyclic drugs for prophylaxis. There are various options for the treatment of trigeminal autonomic cephalalgia syndromes such as cluster headache and paroxysmal hemicrania. For group 4 headaches (other primary headache disorders), the treatment must be chosen on an individual basis; indomethacin is often effective. CONCLUSION: If the patient is clearly suffering from none of the four types of primary headache, the problem must be a headache of a secondary nature, potentially reflecting a dangerous underlying disease. The treatment of headache is usually successful and thus highly rewarding for physicians of all medical specialties. PMID- 29789117 TI - Hemoperitoneum due to delayed gallbladder rupture after abdominal trauma. PMID- 29789118 TI - Septic shock secondary to Mirizzi syndrome resolved in two stages. PMID- 29789119 TI - Hyperostotic esthesioneuroblastoma as a fibrous dysplasia mimicker. PMID- 29789120 TI - SQAB 2017: Quantitative and Comparative Analyses of Behavior. PMID- 29789122 TI - Indexed plasma drug concentrations for drug adherence screening in hypertensive patients. AB - AIM: Due to its high sensitivity, qualitative plasma drug screening by liquid chromatography/tandem mass spectrometry may not be able to distinguish same-day drug intake from drug use on preceding days and cause misclassifications of drug adherence in hypertensive patients. Analysis of plasma drug concentrations may provide more accurate results. PATIENTS AND METHODS: We describe dose-dependent indexing of plasma drug concentrations for expected peak concentrations to define individual screening thresholds for same-day drug use. To explore its utility, plasma samples from 9 hypertensive patients without major comorbidity were prospectively analyzed on two occasions. All were on hydrochlorothiazide with either amlodipine (n=7) and/or valsartan (n=6) at different doses. Drugs were quantitated by mass spectrometry. Non-adherence was defined if an indexed drug concentration was below the expected trough level at 24-hour dosing interval. RESULTS: All patients were adherent by qualitative plasma screening (spectrometric sensitivity). On the first visit (random sampling time), mean plasma concentrations of the drugs were 102+/-70, 15.4+/-6.7 and 2529+/ 1608ng/mL, and mean indexes 84+/-57%, 85+/-35% and 60+/-38%, respectively. Using the study criterion, non-adherence was suspected in three. Intraindividual cross checking retained two. On the second visit (fixed sampling time), amlodipine concentration was 15.6+/-8.5ng/mL (88+/-52% after indexing). Two patients were non-adherent according to the study criterion. CONCLUSION: Indexing of plasma drug concentrations appears practicable and useful for drug adherence screening under clinical conditions. With this technique, same-day drug intake can be easily distinguished which reduces the risk of false positive results associated with qualitative drug screening. PMID- 29789124 TI - Effective utilization of non-invasive enteroscopy. PMID- 29789121 TI - Aire is not essential for regulating neuroinflammatory disease in mice transgenic for human autoimmune-diseases associated MHC class II genes HLA-DR2b and HLA-DR4. AB - The human autoimmune disease-associated HLA alleles HLA-DR2b (DRB1*1501) and HLA DR4 (DRB1*0401) are strongly linked to increased susceptibility for multiple sclerosis (MS) and rheumatoid arthritis (RA), respectively. The underlying mechanisms are not fully understood, but these MHC alleles may shape the repertoire of pathogenic T cells via central tolerance. The transcription factor autoimmune regulator (AIRE) promotes central T cell tolerance via ectopic expression of tissue-specific antigens (TSAs). Aire deficiency in humans causes autoimmune polyendocrinopathy syndrome type 1 (APS1), and Aire knockout mice (Aire-/-) develop spontaneous autoimmune pathology characterized by multi-organ lymphocytic infiltrates. Here, we asked whether impaired TSAs gene expression in the absence of Aire promoted spontaneous MS- or RA-like autoimmune pathology in the context of human HLA alleles in HLA-DR2b or HLA-DR4 transgenic (tg) mice. The results show that reduced TSAs gene expression in the thymus of Aire-deficient HLA-DR2b or HLA-DR4 tg mice corresponded to mild spontaneous inflammatory infiltrates in salivary glands, liver, and pancreas. Moreover, Aire-deficiency modestly enhanced experimental autoimmune encephalomyelitis (EAE) in HLA-DR tg mice, but the animals did not show signs of spontaneous neuroinflammation or arthritis. No significant changes were observed in CD4+ T cell numbers, T cell receptor (TCR) distribution, regulatory T cells (Treg), or antigen-induced cytokine production. Abrogating Treg function by treatment with anti-CTLA-4 or anti-CD25 mAb in Aire-deficient HLA-DR tg mice did not trigger EAE or other autoimmune pathology. Our results suggest a redundant role for Aire in maintaining immune tolerance in the context of autoimmune disease-associated human HLA alleles. PMID- 29789123 TI - Amputation stump perfusion is predictive of post-operative necrotic eschar formation. AB - BACKGROUND: A large proportion of patients develop poor amputation stump healing. We hypothesize that Laser-Assisted Fluorescent Angiography (LAFA) can predict inadequate tissue perfusion and healing. METHODS: Over an 8-month period we reviewed all patients who underwent lower extremity amputation and LAFA. We evaluated intra-operative LAFA global and segmental stump perfusion, and post operative modified Bates-Jensen (mBJS) wound healing scores. RESULTS: In 15 patients, amputation stumps with lower global perfusion demonstrated higher mBJS (P = 0.01). Lower suture-line perfusion also correlated with more eschar formation (P < 0.001). Diabetic patients had higher mBJS (P = 0.009), lower stump perfusion (P = 0.02), and increased eschar volume (P < 0.001). CONCLUSION: LAFA is a useful adjunct for intra-operative stump perfusion assessment and can predict areas of poor stump healing and eschar formation. Diabetic patients seem to be at higher risk of stump eschar formation. PMID- 29789125 TI - Comparison of Changes in mGCIPL Thickness Between Medically and Surgically Treated Eyes With Advanced Glaucoma. PMID- 29789126 TI - A comprehensive review on self-healing of asphalt materials: Mechanism, model, characterization and enhancement. AB - Self-healing has great potential to extend the service life of asphalt pavement, and this capability has been regarded as an important strategy when designing a sustainable infrastructure. This review presents a comprehensive summary of the state-of-the-art investigations concerning the self-healing mechanism, model, characterization and enhancement, ranging from asphalt to asphalt pavement. Firstly, the self-healing phenomenon as a general concept in asphalt materials is analyzed including its definition and the differences among self-healing and some viscoelastic responses. Additionally, the development of self-healing in asphalt pavement design is introduced. Next, four kinds of possible self-healing mechanism and corresponding models are presented. It is pointed out that the continuum thermodynamic model, considering the whole process from damage initiation to healing recovery, can be a promising study field. Further, a set of self-healing multiscale characterization methods from microscale to macroscale as well as computational simulation scale, are summed up. Thereinto, the computational simulation shows great potential in simulating the self-healing behavior of asphalt materials from mechanical and molecular level. Moreover, the factors influencing self-healing capability are discussed, but the action mechanisms of some factors remain unclear and need to be investigated. Finally, two extrinsic self-healing technologies, induction heating and capsule healing, are recommended as preventive maintenance applications in asphalt pavement. In future, more effective energy-based healing systems or novel material-based healing systems are expected to be developed towards designing sustainable long life asphalt pavement. PMID- 29789127 TI - Maternal n-3 polyunsaturated fatty acid dietary supply modulates microglia lipid content in the offspring. AB - The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that are esterified into phospholipids, the major components of cell membranes. They accumulate during the perinatal period when the brain is rapidly developing. Hence, the levels of LC-PUFAs in the brains of the offspring greatly depend on maternal dietary intake. Perinatal n-3 PUFA consumption has been suggested to modulate the activity of microglial cells, the brain's innate immune cells which contribute to the shaping of neuronal network during development. However, the impact of maternal n-3 PUFA intake on microglial lipid composition in the offspring has never been studied. To investigate the impact of maternal dietary n 3 PUFA supply on microglia lipid composition, pregnant mice were fed with n-3 PUFA deficient, n-3 PUFA balanced or n-3 PUFA supplemented diets during gestation and lactation. At weaning, microglia were isolated from the pup's brains to analyze their fatty acid composition and phospholipid class levels. We here report that post-natal microglial cells displayed a distinctive lipid profile as they contained high levels of eicosapentaenoic acid (EPA), more EPA than docosahexaenoic acid (DHA) and large amount of phosphatidylinositol (PI) / phosphatidylserine (PS). Maternal n-3 PUFA supply increased DHA levels and decreased n-6 docosapentaenoic acid (DPA) levels whereas the PI/PS membrane content was inversely correlated to the quantity of PUFAs in the diet. These results raise the possibility of modulating microglial lipid profile and their subsequent activity in the developing brain. PMID- 29789128 TI - Prostaglandin E2 attenuates synergistic bactericidal effects between COX inhibitors and antibiotics on Staphylococcus aureus. AB - PGE2 is found to attenuate the bactericidal effects of kanamycin or ampicillin in Staphylococcus aureus, as well as the methicillin-resistant S. aureus (MRSA). Co treatment with cyclooxygenase (COX) inhibitors (celecoxib, aspirin or naproxen) synergistically enhances kanamycin or ampicillin-induced cell death of S. aureus and MRSA. COX inhibitors repressed bacterial multidrug resistance through down regulating efflux pump activity in antibiotics-treated S. aureus and MRSA. However, this synergistic bactericidal effects are reduced by the treatment with PGE2. PGE2 restores the efflux pump activity as well as increases biofilm formation in S. aureus and MRSA. Collectively, the enhancement of efflux pump activity and biofilm formation with PGE2 might partially explain the resistance to synergistic bactericidal effects between COX inhibitors and antibiotics in PGE2-treated S. aureus. PMID- 29789129 TI - Trends in linoleic acid intake in the United States adult population: NHANES 1999 2014. AB - Linoleic acid (LA), the primary polyunsaturated fatty acid (PUFA) in the US diet, is an essential fatty acid. LA is available from a wide variety of foods, although it is primarily sourced from plant seed oils. Individual-level data on demography and food and nutrient intake were acquired from the NHANES waves 1999 2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012, and 2013 2014. Mean daily intake of (LA) was estimated for each survey wave overall, and by age, gender, educational attainment, race/ethnicity, and income-to-poverty ratio. Linear temporal (1999-2014) trends in LA intake were estimated using univariate linear regression tests, with P < 0.05 and a two-tailed distribution. We found that US adults meet intake recommendation for LA and observed a trend of increasing intake of LA in the US overall and by sub-categories of age, sex, education, race/ethnicity, and income-to-poverty ratio. PMID- 29789130 TI - The effects of alcohol on plasma lipid mediators of inflammation resolution in patients with Type 2 diabetes mellitus. AB - BACKGROUND: Type 2 diabetes mellitus is characterized by peripheral insulin resistance and low-grade systemic inflammation. Inflammation resolution is recognised as an important process driven by specialised pro-resolving mediators of inflammation (SPMs) and has the potential to moderate chronic inflammation. Alcohol has the potential to affect synthesis of SPMs by altering key enzymes involved in SPM synthesis and may influence ongoing inflammation associated with Type 2 diabetes mellitus. AIMS: (i) To examine the effects of alcohol consumed as red wine on plasma SPM in men and women with Type 2 diabetes in a randomised controlled trial and (ii) compare baseline plasma SPM levels in the same patients with those of healthy volunteers. METHODS: Twenty-four patients with Type 2 diabetes mellitus were randomized to a three-period crossover study with men drinking red wine 300 ml/day (~31 g alcohol/day) and women drinking red wine 230 ml/day (~24 g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. The SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), E series resolvins (Rv) (RvE1-RvE3), 17-hydroxydocosahexaenoic acid (17-HDHA), and D-series resolvins (RvD1, 17R-RvD1, RvD2, RvD5), 14-hydroxydocosahexaenoic acid (14-HDHA) and Maresin 1 were measured at the end of each period. A baseline comparison of plasma SPM, hs CRP, lipids and glucose was made with healthy volunteers. RESULTS: Red wine did not differentially affect any of the SPM measured when compared with DRW or water. Baseline levels of the hs-CRP and the SPM 18-HEPE, 17-HDHA, RvD1 and 17R-RvD1 in patients with Type 2 diabetes mellitus were all significantly elevated compared with healthy controls and remained so after adjusting for age and gender. CONCLUSION: Moderate alcohol consumption as red wine does not alter plasma SPM in patients with Type 2 diabetes mellitus. The elevation of SPM levels compared with healthy volunteers may be a homeostatic response to counter ongoing inflammation. PMID- 29789131 TI - Randomized trials of replacing saturated fatty acids with n-6 polyunsaturated fatty acids in coronary heart disease prevention: Not the gold standard? AB - Several trials in the 1950s through 1970s tested the hypothesis that replacing saturated fat in the diet predominantly with n-6 polyunsaturated fat (PUFA) would reduce the incidence of coronary heart disease (CHD), mainly through modifying blood lipid profile. Most of these trials did observe a reduction in serum total cholesterol in the intervention group, but many trials failed to find a significant reduction in the incidence of CHD. However, some meta-analyses have found a reduced incidence of CHD by pooling the results from the trials. Recently, new recovered and reanalyzed data has emerged from two of the old trials. The new findings seemed to counteract the classical diet-heart hypothesis, when they found no cardiovascular benefit and even suggested harm, despite reduction in the serum total cholesterol concentration after replacing saturated fat especially with n-6 PUFA. This has raised criticism regarding the validity of the dietary recommendations that suggest partially replacing saturated fats with n-6 PUFA. This paper introduces the classical diet-heart trials and their main results and how the new findings relate to the overall study data of the cardiovascular effects of the n-6 PUFA. For multiple reasons considered here, it is difficult to draw firm conclusions of the cardiovascular effects of the n-6 PUFA based only on the findings in the old diet-heart trials. A more comprehensive picture emerges when also other lines of evidence is considered. The overall study data, including findings also from prospective cohort studies and from dietary trials with intermediate outcomes, still suggests that replacing saturated fat with n-6 PUFA would rather be beneficial than harmful for the prevention of CHD. PMID- 29789132 TI - Inverted diverticulum of the colon - a cautious diagnosis. PMID- 29789133 TI - Eosinophilic pneumonia induced by non-steroidal anti-inflammatory drugs: An underestimated risk. AB - INTRODUCTION: Eosinophilic pneumonia (EP) is a rare but serious adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: We describe the second published case of EP induced by oral diclofenac. We also reviewed the literature as well as French pharmacovigilance database. Case presentation A 63 year-old woman with polyarthralgia had taken diclofenac for three days for analgesic purposes. Progressively, the patient presented weakness, dyspnea and fever. Computed tomography (CT) scan revealed bilateral interstitial infiltration. Broncho-alveolar lavage (BAL) showed an elevated level of eosinophils. After ruling out all other possible etiologies, drug-induced EP was diagnosed and treatment by corticosteroid was initiated. The patient recovered in three months. RESULTS: In the French pharmacovigilance database, six cases of EP were recorded (3 with naproxen, 2 with ibuprofen, 1 with piroxicam). In the literature, twenty-six cases of EP with NSAIDs were published. The most commonly involved drug was naproxen (n=8), followed by fenbufen (n=4), ibuprofen (n=3) and diclofenac (n=2). A high level of eosinophils was systematically observed in the blood cell count or BAL. Corticosteroid therapy was started in eleven cases. All patients recovered. CONCLUSION: Complete history taking and examination should be done to rule out other etiological diagnoses. BAL is sufficient to diagnose EP. Corticosteroid therapy should be indicated for more severe or refractory cases. This adverse drug reaction is underestimated, healthcare professionals should be informed. PMID- 29789134 TI - Fluoroscopy-guided removal of individualised airway-covered stents for airway fistulas. AB - AIM: To report the techniques and complications associated with fluoroscopy guided removal of individual covered stents for airway fistula disease over a 6 year period. MATERIALS AND METHODS: A retrospective analysis was conducted of 85 patients, 72 male and 13 female, who underwent fluoroscopy-guided stent removal from January 2011 to June 2017. Patients ranged in age from 15 to 81 years (mean, 54.9+/-12.3 years). Before removal, 90 stents had been placed for airway fistula disease. All patients underwent diagnostic flexible bronchoscopy and airway computed tomography (CT) prior to stent removal. The indications for stent removal and post-interventional complications were analysed. RESULTS: Eighty-nine of 90 airway stents were successfully removed from 85 consecutive patients, for a technique success rate of 98.9%. Of these, 14 stents showed strut fracture, one stent showed retained stent pieces, and the remaining 75 stents were removed in one piece. Indications for stent removal included regular removal (n=46), stent migration (n=11), excessive granulation tissue (n=10), strut fracture (n=4), intolerance of stenting (n=6). Complications of stent removal were as follows: retained stent pieces (n=1), mucosal tear with massive bleeding (n=2), re obstruction requiring stenting (n=1), dyspnoea with mechanical ventilation needed (n=1), and dyspnoea with oxygen inhalation needed (n=1). CONCLUSIONS: Airway stents can be safely removed under fluoroscopy guidance. Removal after 31-90 days is recommended for removal to avoid excessive granulation tissue. PMID- 29789135 TI - Combined effects of ocean acidification and temperature on planula larvae of the moon jellyfish Aurelia coerulea. AB - Rapidly rising levels of atmospheric CO2 have caused two environmental stressors, ocean acidification and seawater temperature increases, which represent major abiotic threats to marine organisms. Here, we investigated for the first time the combined effects of ocean acidification and seawater temperature increases on the behavior, survival, and settlement of the planula larvae of Aurelia coerulea, which is considered a nuisance species around the world. Three pH levels (8.1, 7.7 and 7.3) and two temperature levels (24 degrees C and 27 degrees C) were used in the present study. There were no interactive effects of temperature and pH on the behavior, survival, and settlement of planula larvae of A. coerulea. We found that the swimming speed and mortality of the planula larvae of A. coerulea were significantly affected by temperature, and low pH significantly affected settlement. Planula larvae of A. coerulea from the elevated temperature treatment moved faster and showed higher mortality than those at the control temperature. The settlement rate of A. coerulea planulae was significantly higher at the pH level of 7.3 than at other pH levels. These results suggest that seawater temperature increase, rather than reduced pH, was the main stress factor affecting the survival of A. coerulea planulae. Overall, the planula larvae of the common jellyfish A. coerulea appeared to be resistant to ocean acidification, but may be negatively affected by future seawater temperature increases. PMID- 29789136 TI - Penetrating trauma in children on the United States-Mexico border: Hispanic ethnicity is not a risk factor. AB - INTRODUCTION: The United States-Mexico border is perceived as dangerous by the media and current political leaders. Hispanic ethnicity, low socioeconomic status, male gender and adolescent age have previously been identified as risk factors for penetrating trauma (PT). METHODS: A retrospective review of PT was performed in a border region. Children 0-17 years old, admitted to the region's only level I trauma center between 2001 and 2016 were included. Standardized morbidity ratio was used to compare observed to expected morbidity. RESULTS: There were 417 PT admissions. 197 (47%) were non-accidental, 34 (8%) suicide attempts and 186 (45%) accidental. There were 12 homicides, 7 suicides and no accidental deaths. The region contains over 280,000 children, thus yielding a homicide rate of 0.26 per 100,000. The U.S. pediatric homicide rate was 2.6-4.0 over this period. Adolescents 13-17 years old accounted for 237 (57%) admissions, 152 (78%) of non-accidental admissions and 12 (63%) deaths. Most admissions (N = 321, 77%) and 15 of the deaths (79%) were males. Non-accidental injuries were more frequent in ZIP codes associated with low incomes. Hispanic patients accounted for 173 (88%) of non-accidental trauma. However, 40 (20%) non accidental injuries occurred in Mexico and 157 (80%) injuries occurred in an 82% Hispanic region. Therefore, the standardized morbidity ratio for Hispanic ethnicity was 1.048 (CL 0.8-1.2, P = 0.6). CONCLUSION: On the United States Mexico border, the pediatric homicide rate was less than 1/10 the national average. Male adolescents are at risk for non-accidental PT. In a Hispanic majority population, Hispanic ethnicity was not a risk factor for PT. It is possible that economic disparity, rather than race/ethnicity, is a risk factor for PT. PMID- 29789137 TI - Serratus-intercostal interfascial block as an opioid-saving strategy in supra umbilical open surgery. AB - INTRODUCTION: The administration of local anaesthetic in the serratus-intercostal space provides adequate analgesia in non-reconstructive breast surgery. The aim of this study was to evaluate whether the blockage of the last intercostal nerves (T7-T11) can lead to opioid savings in supra-umbilical open surgery procedures. MATERIAL AND METHODS: A prospective observational study was conducted on patients undergoing open supra-umbilical surgery under general anaesthesia and with a serratus-intercostal plane block [modified Blocking the bRanches of IntercostaL nerves in the Middle Axillary line (BRILMA)] as an associated analgesic strategy. Post-operative pain was assessed with the numerical verbal scale (NVS 0 to 10) on admission to the post-anAesthesia recovery unit, at 6, 12, 24, and 48h postintervention and by need for analgesic rescues with opioids (2mg iv of morphine, if values higher than 3 in NVS). Adverse events related to the technique were also recorded. The statistical package used in the analysis of the data was SPSS(r) for Windows. RESULTS: The study recruited 52 patients. Differences, with a p<.05, were found intra-operatively in the consumption of fentanyl: 400 + 80MUg versus 110 + 50MUg in patients who underwent pre-incisional blockade. In the first 24hours, only 3 cases (two gastrectomies and one cholecystectomy) required morphine (single bolus of 2mg). Between 24h and 48h it was necessary to administer several morphine boluses (8 + 2mg) in four patients (three gastrectomies and one cholecystectomy). Four patients presented with nausea and / or vomiting and there were no complications related to the analgesic technique. CONCLUSION: The intercostal nerves block (T7-T11) in the serratus intercostal space may constitute an opioid-sparing analgesic strategy in open supra-umbilical surgery. PMID- 29789138 TI - Introduction to primary hemifacial spasm: A neurosurgical disease. AB - Primary hemifacial spasm is a hyperactive cranial nerve syndrome. The cause is always a neurovascular compression, generally at the root exit zone from the brainstem. Its curative treatment is microvascular decompression, that may be performed as a first option, or secondarily when botulinum toxin injections fail. PMID- 29789139 TI - Medical and Preoperative Evaluation of the Older Adult. AB - Because of age, increased rates of multimorbidity, polypharmacy, functional changes, and cognitive impairment, older adults are at higher risk for perioperative complications. Identifying modifiable risk factors and educating patients and families about what to expect can improve surgical outcomes and satisfaction. Comprehensive preoperative evaluation assesses these potential factors and should include recommendations for risk reduction. The optimal preoperative evaluation for older adults should address medical conditions and other areas pertinent to the care of older adults including assessments of cognition, capacity, delirium risk, function, frailty, nutrition, medications, and treatment preferences. PMID- 29789140 TI - Changes in concentrations of tau-reactive antibodies are dependent on sex in Alzheimer's disease patients. AB - The presence of pre-existing natural antibodies against Alzheimer's disease (AD) pathological proteins might interfere with immune responses to therapeutic vaccination with these proteins. We aimed to compare levels of antibodies in CSF and serum: We observed higher reactivity of natural tau-reactive antibodies towards phosphorylated bovine tau protein than to human recombinant (non phosphorylated) tau protein. Males with MCI-AD had higher amounts of these antibodies than corresponding controls. Concentrations of antibodies were lower in females with the MCI-AD than in control females. These findings may have implications for tau vaccination trials. PMID- 29789142 TI - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases. AB - INTRODUCTION: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern. PATIENTS AND METHODS: We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea. RESULTS AND DISCUSSION: The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions. PMID- 29789141 TI - Patterns of peritraumatic threat perceptions in patients evaluated for suspected acute coronary syndrome according to prior and current posttraumatic stress symptoms. AB - OBJECTIVE: Prior posttraumatic stress disorder (PTSD) and elevated threat perceptions predict posttraumatic psychopathology after evaluation for acute coronary syndrome (ACS), but most research has measured threat retrospectively. We investigated how threat perceptions during ACS evaluation in the emergency department (ED) and upon recall were associated with posttraumatic psychopathology burden due to prior trauma and the suspected ACS. METHODS: Perceived threat was assessed in the ED, and ED threat recall was assessed upon inpatient transfer/discharge, along with acute stress disorder (ASD) symptoms due to suspected ACS and PTSD symptoms due to prior trauma. The sample comprised 894 participants (mean age = 60.7 +/- 13.1 years; 46.8% female; 56.3% Hispanic; 20.5% Black). One-way ANOVAs examined how those with consistent posttraumatic psychopathology (prior PTSD/ASD; 14.8%), prior posttraumatic psychopathology (prior PTSD/no ASD; 6.8%), new-onset posttraumatic psychopathology (no PTSD/ASD; 15.7%), or no posttraumatic psychopathology (no PTSD/no ASD; 62.8%) differed in threat perception, threat recall, and their discrepancy. RESULTS: Threat perception scores ranged from 6 to 24. Participants with consistent posttraumatic psychopathology had higher threat perceptions (M = 14.01) than those with prior posttraumatic psychopathology (M = 12.02) and new-onset posttraumatic psychopathology (M = 12.21) (ps <= 0.001); the latter two did not differ significantly but had higher threat perceptions than those with no posttraumatic psychopathology (M = 9.84) (p < .001). Similar results were observed for threat recall (p < .001). The new-onset posttraumatic psychopathology group also had a greater increase in perceived threat versus the no posttraumatic psychopathology group (p = .06). Results were similar adjusting for potential confounders. CONCLUSIONS: Assessing threat perceptions during ACS evaluation and hospitalization may help identify those at risk for emotional difficulties post ACS. PMID- 29789143 TI - Skin necrosis after septic shock. PMID- 29789144 TI - Papillon-Lefevre Syndrome: A case report. PMID- 29789145 TI - Corrigendum to "Preparation and characterization of antibacterial, eco-friendly edible nanocomposite films containing Salvia macrosiphon and nanoclay" [Int. J. Biol. Macromol. 113(2018) 66-72]. PMID- 29789146 TI - Muir-Torre syndrome. PMID- 29789147 TI - Long-term outcomes of isolated superficial vein thrombosis in patients with active cancer. AB - BACKGROUND: Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown. METHODS: Data from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex). RESULTS: Cancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6-1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5-23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), similar to that of cancer patients with DVT (adjusted cause-specific HR (aCHR) = 1.5[0.4-5.8]) and higher to that of SVT patients without cancer (aCHR = 2.9[0.7-11.9]). In our population, venous thrombosis on varicose veins was associated with a lower risk of death (aHR = 0.6[0.3-1.0]) and DVT-PE recurrence (aCHR = 0.6[0.2-1.7]). CONCLUSION: Our results suggest that cancer patients with SVT have a poor prognosis, similar to that of patients with cancer-related DVT. The high rate of DVT-PE recurrence suggests that such patients may need longer duration of anticoagulant treatment. PMID- 29789148 TI - Breakthrough dynamics of s-metolachlor metabolites in drinking water wells: Transport pathways and time to trend reversal. AB - We present the results of a two years study on the contamination of the Luxembourg Sandstone aquifer by metolachlor-ESA and metolachlor-OXA, two major transformation products of s-metolachlor. The aim of the study was twofold: (i) assess whether elevated concentrations of both transformation products (up to 1000 ng/l) were due to fast flow breakthough events of short duration or the signs of a contamination of the entire aquifer and (ii) estimate the time to trend reversal once the parent compound was withdrawn from the market. These two questions were addressed by a combined use of groundwater monitoring, laboratory experiments and numerical simulations of the fate of the degradation products in the subsurface. Twelve springs were sampled weekly over an eighteen month period, and the degradation rates of both the parent compound and its transformation products were measured on a representative soil in the laboratory using a radiolabeled precursor. Modelling with the numeric code PEARL simulating pesticide fate in soil coupled to a simple transfer function model for the aquifer compartment, and calibrated from the field and laboratory data, predicts a significant damping by the aquifer of the peaks of concentration of both metolachlor-ESA and -OXA leached from the soil. The time to trend reversal following the ban of s-metolachlor in spring protection zones should be observed before the end of the decade, while the return of contaminant concentrations below the drinking water limit of 100 ng/l however is expected to last up to twelve years. The calculated contribution to total water discharge of the fast flow component from cropland and short-circuiting the aquifer was small in most springs (median of 1.2%), but sufficient to cause additional peaks of concentration of several hundred nanograms per litre in spring water. These peaks are superimposed on the more steady contamination sustained by the base flow, and should cease immediately once application of the parent compound stops. PMID- 29789149 TI - The expanding role of murine class Ib MHC in the development and activation of Natural Killer cells. AB - Major Histocompatibility Complex-I (MHC-I) molecules can be divided into class Ia and class Ib, with three distinct class Ib families found in the mouse. These families are designated as Q, T and M and are largely unexplored in terms of their immunological function. Among the class Ib MHC, H2-T23 (Qa-1b) has been a significant target for Natural Killer (NK) cell research, owing to its homology with the human class Ib human leukocyte antigen (HLA)-E. However, recent data has indicated that members of the Q and M family of class Ib MHC also play a critical role in the development and regulation NK cells. Here we discuss the recent advances in the control of NK cells by murine class Ib MHC as a means to stimulate further exploration of these molecules. PMID- 29789150 TI - Compensation for inertial and gravity effects in a moving force platform. AB - Force plates for human movement analysis provide accurate measurements when mounted rigidly on an inertial reference frame. Large measurement errors occur, however, when the force plate is accelerated, or tilted relative to gravity. This prohibits the use of force plates in human perturbation studies with controlled surface movements, or in conditions where the foundation is moving or not sufficiently rigid. Here we present a linear model to predict the inertial and gravitational artifacts using accelerometer signals. The model is first calibrated with data collected from random movements of the unloaded system and then used to compensate for the errors in another trial. The method was tested experimentally on an instrumented force treadmill capable of dynamic mediolateral translation and sagittal pitch. The compensation was evaluated in five experimental conditions, including platform motions induced by actuators, by motor vibration, and by human ground reaction forces. In the test that included all sources of platform motion, the root-mean-square (RMS) errors were 39.0 N and 15.3 N m in force and moment, before compensation, and 1.6 N and 1.1 N m, after compensation. A sensitivity analysis was performed to determine the effect on estimating joint moments during human gait. Joint moment errors in hip, knee, and ankle were initially 53.80 N m, 32.69 N m, and 19.10 N m, and reduced to 1.67 N m, 1.37 N m, and 1.13 N m with our method. It was concluded that the compensation method can reduce the inertial and gravitational artifacts to an acceptable level for human gait analysis. PMID- 29789152 TI - Discussion. PMID- 29789151 TI - Surgical algorithm and results for repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. AB - OBJECTIVE: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is a complex and heterogeneous form of congenital heart disease. There is a controversy regarding the optimal treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. The purpose of this study was to summarize our algorithm and surgical results for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. METHODS: This was a retrospective review of 307 patients undergoing primary surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Excluded from this analysis were patients who had undergone prior surgical treatment at another institution and patients with single ventricle and major aortopulmonary collateral arteries. There were 3 surgical pathways, including midline unifocalization (n = 241), creation of an aortopulmonary window (n = 46), and other (n = 20). RESULTS: For the 241 patients who underwent midline unifocalization, 204 (85.4%) had a single-stage complete repair. There were 37 patients who underwent a midline unifocalization and central shunt, and 24 have subsequently undergone complete repair. Forty-six patients underwent an aortopulmonary window, of whom 36 have subsequently had a complete repair. There were 20 patients who had complex anatomy and underwent procedures other than described, and14 have subsequently undergone complete repair. Thus, for the patients currently eligible, 280 (93.0%) have achieved complete repair. For the 204 patients who had a single-stage complete repair, the mean right ventricle to aortic pressure ratio was 0.36 +/- 0.09. Seventy-six patients underwent a staged repair, and the mean right ventricle to aortic pressure ratio was 0.40 +/- 0.09 (P < .05 compared with single-stage repair). There were 3 (1.5%) early and 8 (4.0%) late deaths for the single-stage complete repair cohort versus 4 (4.0%) early and 15 (14.9%) late deaths for all other procedures (P < .01). CONCLUSIONS: The data demonstrate that more than 90% of patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries achieved complete repair. The overall mortality was significantly lower in the subgroup of patients who underwent single-stage complete repair. PMID- 29789153 TI - Adjunct retrograde cerebral perfusion provides superior outcomes compared with hypothermic circulatory arrest alone: A meta-analysis. AB - OBJECTIVE: Retrograde cerebral perfusion is becoming less frequently used as a method of neuroprotection during aortic surgery. The present meta-analysis aims to compare outcomes after arch surgery with hypothermic circulatory arrest versus hypothermic circulatory arrest + retrograde cerebral perfusion. METHODS: Electronic searches were performed using 7 databases from their inception to September 2016. Relevant comparative studies that included patient groups who underwent aortic arch surgery using hypothermic circulatory arrest with continuous retrograde cerebral perfusion or hypothermic circulatory arrest alone were identified, and data were extracted by 2 independent researchers. Data were aggregated using a random-effects model per predefined clinical end points. RESULTS: Twenty-eight comparative studies were identified, with 2705 hypothermic circulatory arrest cases and 2817 hypothermic circulatory arrest + retrograde cerebral perfusion cases. No significant differences were seen between both groups in terms of age, gender, proportion of dissections and aneurysms, and hemiarch/total arch repair. The hypothermic circulatory arrest + retrograde cerebral perfusion group had slightly longer cardiopulmonary bypass time and lower body arrest time. Mortality was significantly increased for the hypothermic circulatory arrest cohort compared with the hypothermic circulatory arrest + retrograde cerebral perfusion cohort (odds ratio, 1.75; 95% confidence interval, 1.16-2.63; P = .007; I2 = 54%), but not on pooling of adjusted estimates. Stroke was also increased for the hypothermic circulatory arrest cohort (odds ratio, 1.50; 95% confidence interval, 1.07-2.10; P = .02; I2 = 29%). No difference in temporary neurologic deficit was identified (P = .66). Meta-regression found the treatment effect for mortality and stroke to be less pronounced in more contemporary series. CONCLUSIONS: These results suggest that the addition of retrograde cerebral perfusion during aortic arch surgery may provide better outcomes than using hypothermic circulatory arrest alone, although significant confounders exist. Further robust studies are required to confirm the utility of retrograde cerebral perfusion in arch surgery. PMID- 29789154 TI - Improved prescribed performance control for air-breathing hypersonic vehicles with unknown deadzone input nonlinearity. AB - An improved prescribed performance controller is proposed for the longitudinal model of an air-breathing hypersonic vehicle (AHV) subject to uncertain dynamics and input nonlinearity. Different from the traditional non-affine model requiring non-affine functions to be differentiable, this paper utilizes a semi-decomposed non-affine model with non-affine functions being locally semi-bounded and possibly in-differentiable. A new error transformation combined with novel prescribed performance functions is proposed to bypass complex deductions caused by conventional error constraint approaches and circumvent high frequency chattering in control inputs. On the basis of backstepping technique, the improved prescribed performance controller with low structural and computational complexity is designed. The methodology guarantees the altitude and velocity tracking error within transient and steady state performance envelopes and presents excellent robustness against uncertain dynamics and deadzone input nonlinearity. Simulation results demonstrate the efficacy of the proposed method. PMID- 29789155 TI - Endocrine and metabolic profile of peripubertal Standardbred colts. AB - The objectives of this study were to determine the concentrations of reproductive and metabolic hormones during the peripubertal period and to assess their relationship with testicular development and body fat deposition. Blood samples were collected from 23 healthy Standardbred colts every four weeks for twelve months. Colts were weighed monthly, and percent of body fat and testicular volume estimated by ultrasound. Onset of puberty was determined as the month when testosterone was two standard deviations above the previous mean. Plasma FSH, LH, leptin, estradiol-17beta, androstenedione, IGF-1, insulin, inhibin-A, and inhibin B were analyzed for a seven month peripubertal period. Spring born Standardbred colts underwent puberty at 13 months of age; onset of puberty coincided with exponential testicular growth but did not coincide with an increase in cutaneous body fat deposition or leptin (p > 0.05). Plasma inhibin-B concentrations were significantly increased in the postpubertal period (p < 0.05), but no increase was seen in inhibin-A, androstenedione, FSH, LH, or estradiol-17beta. In conclusion, the rise in testosterone and subsequent onset of puberty coincides with rapid testicular growth but is not correlated with an increase in gonadotropins, IGF-1, cutaneous body fat or leptin in the horse. PMID- 29789156 TI - Comparing corneal higher-order aberrations in corneal wavefront-guided transepithelial photorefractive keratectomy versus small-incision lenticule extraction. AB - PURPOSE: To evaluate the changes in corneal higher-order aberrations (HOAs) after corneal wavefront-guided transepithelial photorefractive keratectomy (PRK) and small-incision lenticule extraction (SMILE). SETTING: Yonsei University College of Medicine and Eyereum Eye Clinic, South Korea. DESIGN: Retrospective case series. METHODS: Medical records of patients having either corneal wavefront guided transepithelial PRK or small-incision lenticule extraction were examined. The root-mean-square total HOAs, 3rd-order coma aberration, and 4th-order spherical aberration were measured preoperatively and 6 months postoperatively. Independent t tests and analysis of covariance were used to compare changes in corneal HOAs between the 2 groups. RESULTS: The study comprised 77 eyes having corneal wavefront-guided transepithelial PRK and 81 eyes having small-incision lenticule extraction. The total HOAs and spherical aberration increased after transepithelial PRK (all P < .001), whereas coma aberration was stable after transepithelial PRK. The total HOAs, spherical aberration, and coma aberration increased after small-incision lenticule extraction (P < .001 for total HOAs, spherical aberration; P = .004 for coma). At 6 months postoperatively, total HOAs and spherical aberration were significantly larger in the transepithelial PRK group than in the small-incision lenticule extraction group. Coma aberration was larger in the small-incision lenticule extraction group than in the transepithelial PRK group. Spherical aberration induction was significantly smaller in the small-incision lenticule extraction group than in the transepithelial PRK group (P < .001), and coma aberration induction was larger in the small-incision lenticule extraction group than in the transepithelial PRK group (P = .011). CONCLUSIONS: Small-incision lenticule extraction demonstrated that the induction of total HOAs was comparable to corneal wavefront-guided transepithelial PRK, accompanied by smaller spherical aberration induction and larger coma aberration induction. During small-incision lenticule extraction, surgeons should aim to obtain optimum centration for smaller induction of corneal HOAs. PMID- 29789157 TI - Comparison of fibrotic response in the human lens capsular bag after femtosecond laser-assisted cataract surgery and conventional phacoemulsification. AB - PURPOSE: To compare the effect of different laser pulse energy settings in femtosecond laser-assisted cataract surgery with that of standard phacoemulsification and no energy at all used on posterior capsule opacification (PCO) in vitro. SETTING: Cell and Molecular Biology Research Laboratory, Department of Ophthalmology, Ludwig-Maximilians-University Munich, Real Eyes, Ophthalmology Center, Munich, and Institute for Clinical Pathology, Goethe University Frankfurt, Frankfurt, Germany. DESIGN: Experimental study. METHODS: Fifteen cadaver capsular bags were cultivated from 8 human donors under standard cell culture conditions. For preparation of the capsular bag, 4 groups were established as follows: femtosecond laser-assisted cataract surgery standard energy (n = 3), femtosecond laser-assisted cataract surgery high energy (n = 3), phacoemulsification (n = 6), and hydrodissection without energy (extracapsular cataract extraction) (n = 3). Growth of lens epithelial cells was observed and photodocumented. The days until full cell coverage of the posterior capsule were documented. Capsular bags were stained for fibronectin, alpha-smooth muscle actin, and collagen type 1. RESULTS: Cell growth patterns in all treatment groups were comparable, with no statistically significant differences detected at any timepoint measured (P = .81, Kruskal-Wallis). The markers for fibrosis were equally distributed in all groups, indicating an equal fibrotic reaction in all groups. CONCLUSION: Femtosecond laser-assisted cataract surgery did not increase different cellular responses in PCO formation comparison with phacoemulsification in vitro, even when higher laser pulse energy levels were used. PMID- 29789158 TI - Rap1 promotes proliferation and migration of vascular smooth muscle cell via the ERK pathway. AB - BACKGROUND: Rap1 is involved in a multitude of cellular signal transduction pathways, which has extensively been linked to cell proliferation and migration. It has been shown to be important in the regulation of physiological and pathological processes. The present study aims to elucidate its detailed mechanistic in proliferation and migration. MATERIAL/METHODS: Vascular smooth muscle cells (VSMCs) were transfected with pcDNA3.1(empty vector), pcDNA3.1 containing Myc-Tagged-Rap1V12 (Rap1V12) or pcDNA3.1 containing Flag-Tagged Rap1GAP (Rap1GAP).The cells were presence or absence with 8CPT-2'OMe-cAMP or SDF 1 before transfection. The proliferation and migration were examined by 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and transwell analysis, respectively. Afterwards, western blot was performed to detect the expression of ERK, phosphorylated-ERK, Rap1, Rap1GAP and Rap1GTP. RESULTS: The results showed that proliferation, migration and the expression of Rap1, Rap1GAP, p-EKR were boosted in treatment of Rap1V12-transfection. However, Rap1GAP presented the opposite effects. Subsequently, VSMCs were pretreatment with stimulators Rap1 guanine exchange factor (Rap1GEF), 8CPT-2'OMe-cAMP and stromal cell-derived factor 1 (SDF-1), then transfected with different vectors and the expression of Rap1, Rap1GAP and p-EKR were obviously decreased. CONCLUSIONS: Taken together, these findings indicated for the first time that Rap1 was essential for the VSMCs in proliferation and migration by ERK signaling pathway. PMID- 29789159 TI - Chickenpox: An update. AB - Despite its benign characteristics, chickenpox is a childhood disease responsible for complications and deaths, particularly in the high-risk population. VariZIG(r), not commercialized in France, is a good alternative for seronegative individuals exposed to the virus and not eligible for vaccination. The efficacy of routine vaccination has been demonstrated with a decrease in chickenpox incidence and with the development of herd immunity. Over time, the protective antibody titer of vaccinated people decreases and can be maintained by two doses of the vaccine. A tetravalent measles-mumps-rubella-chickenpox vaccine, used in the United States, has a good tolerability in spite of the occurrence of fever and febrile seizures. Routine vaccination would contribute to make savings in France, by reducing direct and indirect costs of chickenpox. PMID- 29789160 TI - Pneumocystosis and quantitative PCR. AB - OBJECTIVE: Pneumocystis pneumonia (PCP) is now predominantly observed in immunosuppressed non-HIV-infected patients. The sensitivity of the PCR is here higher than direct examination (DE) of respiratory secretions because the infection is caused by a lower inoculum of Pneumocystis jirovecii (P. jirovecii). The objective of our retrospective study was to assess the contribution of quantitative PCR (qPCR) in the diagnosis of PCP. PATIENTS AND METHODS: All patients hospitalized for PCP suspicion with a positive qPCR were included. Irrespective of the qPCR value, patients were initially classified into two groups (infection and colonization [PCP ruled out]) based on clinical, radiological, and microbiological data. Both groups were then compared based on the qPCR value. RESULTS: Between 2013 and 2016, 150 patients were included; 75% of them were not infected with HIV. The diagnosis of PCP was retained for 129 patients and rejected for 21 patients. The DE was negative in 60% of PCP cases. The median value of qPCR was 76,650copies/mL among infected patients and 3220copies/mL among colonized patients. The threshold corresponding to a specificity of 100% was 56,000copies/mL. The optimal value to distinguish an infection from a colonization was 10,100copies/mL. CONCLUSION: Our study confirms the diagnostic value of the qPCR in immunosuppressed patients, especially when the DE is negative. When the qPCR is?56,000copies/mL, the result should be interpreted based on the clinical context and paraclinical examinations. PMID- 29789161 TI - Synthesis of silver-containing calcium aluminate particles and their effects on a MTA-based endodontic sealer. AB - OBJECTIVE: To synthetize calcium aluminate (C3A) and silver-containing C3A particles (C3A+Ag) testing their effects on the properties of a MTA-based endodontic sealer in comparison to an epoxy resin- and a calcium silicate-based sealer. METHODS: Pure C3A and C3A+Ag particles were synthesized by a chemical method and characterized using XRD to identify crystalline phases. SEM/EDS analysis investigated morphology, particle size, and elemental composition of particles. Setting time, flow, radiopacity, water sorption and solubility of commercial and modified sealers were evaluated according to ISO 6876/2012. The pH and ions release were measured using a pHmeter and a microwave induced plasma optical emission spectrometer. The inhibition of biofilm growth was evaluated by confocal laser scanning microscopy (CLSM). Data were rank transformed and analyzed by ANOVA and Tukey test (P<0.05). RESULTS: The C3A particles showed an irregular grain agglomerated structure with voids and pores. In C3A+Ag particles, Ag modified the material morphology, confirming the deposition of Ag. The physicochemical properties of the modified MTA-based sealer were similar to the commercial material, except for the significant increase in Ca+2 release. However, there was no Ag release. Setting time, flow, radiopacity, water sorption and solubility were adequate for all materials. All the materials showed alkaline pH. Antibiofilm effect was improved in the presence of C3A particles, while the biofilm inhibition was lower in the presence of Ag. SIGNIFICANCE: The modified sealer presented improved antibiofilm properties and calcium release, without dramatic effects on the other characteristics. It is expected a positive effect in its antimicrobial behavior. PMID- 29789162 TI - Fatigue failure load of an adhesively-cemented lithium disilicate glass-ceramic: Conventional ceramic etching vs etch & prime one-step primer. AB - OBJECTIVES: To evaluate the effect of different glass-ceramic surface treatments and aging on the fatigue failure load of a lithium disilicate glass-ceramic adhesively cemented to a dentin analogue material. METHODS: One hundred and twenty (120) disc-shaped lithium disilicate specimens (O=10mm, thickness=1.5mm) were produced and randomly allocated (n=20) into 6 groups, considering 2 study factors: "surface treatment" in 3 levels (SIL-silane application only; HF5+SIL-5% hydrofluoric acid etching and silane application; ME&P-etching with an one-step ceramic primer), and "storage" in 2 levels (baseline-storage for 7 days; aging storage for 90 days+12,000 thermal cycles). Ceramic discs were adhesively cemented to discs of a dentin analogue material (O=10mm, thickness=2.0mm) following the manufacturers' instructions. The fatigue failure load was determined by the staircase approach (250,000 cycles; 20Hz; initial load=1050N [~70% of mean load-to-failure]; step size=52.5N [5% of initial load]). Micro morphologic, fractographic, and atomic force microscope analysis were also performed. Fatigue failure load data were evaluated by one-way ANOVA, Bonferroni and t-tests for independent samples. RESULTS: HF5+SIL presented higher fatigue failure load in both conditions (baseline and aging); ME&P presented intermediary mean values, while the SIL group presented the worst performance. All groups had a statistically significant decrease in the fatigue performance after aging. SIGNIFICANCE: Hydrofluoric acid followed by silane application showed the best fatigue performance for an adhesively-cemented lithium disilicate ceramic. Aging negatively influenced the fatigue performance for all tested groups. PMID- 29789163 TI - Biodegradation of resin-dentin interfaces is dependent on the restorative material, mode of adhesion, esterase or MMP inhibition. AB - OBJECTIVE: To measure the effect of simulated human salivary esterases (SHSE) and metalloproteinases (MMP) inhibition on the integrity of restoration-tooth interfaces made from traditional or polyacid-modified resin composites bonded to human dentin by either total-etch or self-etch adhesives. METHODS: Resin-dentin specimens, made from traditional (Z250) or polyacid-modified (Dyract-eXtra) composites were bonded to human dentin using total-etch (TE-Scotchbond) or self etch (SE-EasyBond) adhesives. TE was applied with or without the MMP inhibitor galardin. Specimens were incubated in phosphate-buffer or SHSE (37 degrees C/pH=7.0) for up to 180 days, then suspended in a continuous flow biofilm fermenter cultivating biofilms of Streptococcus mutans UA159. Interfacial bacterial penetration, biofilm biomass and viability were measured by confocal laser scanning microscopy and biomarker dyes and used as interfacial biodegradation markers. RESULTS: All specimens showed increased biofilm penetration and biomass with time regardless of incubation condition. SHSE increased bacterial penetration in all experimental samples after 180days (p<0.05). Galardin reduced interfacial bacterial ingress and bacterial biomass vs. non-MMP-inhibited TE-bonded specimens (p<0.05). TE interfaces showed lower interfacial bacterial biomass vs. SE after 90-day and 180-day (p<0.05). Dyract eXtra specimens showed lower bacterial cell viability within the interface vs. Z250 (p<0.05). SIGNIFICANCE: The biodegradation of resin-tooth interfaces is accelerated by esterases, modulated by MMP inhibition and is dependent on the material's chemistry and mode of adhesion. The in vitro bacterial growth model used in this study facilitates the elucidation of differences in interfacial integrity and biostability between different materials and techniques and is suitable for assessment of their performance prior to clinical evaluation. PMID- 29789164 TI - [Health system, primary care and public health]. PMID- 29789165 TI - [Study of obesity in a rural children population and its relationship with anthropometric variables]. AB - GOALS: To know the prevalence of obesity in primary and secondary school students, and to evaluate the diagnostic accuracy of anthropometric variables for its detection. DESIGN: Cross-sectional study. LOCATION: Rural area of Cordoba. In the year 2014. PARTICIPANTS: Student population. A stratified sampling was performed according to age, gender and educational centers. A total of 323 students from 6 to 16 years were included in the study, all parents had signed informed consent. MAIN MEASUREMENTS: The prevalence of obesity was determined and sociodemographic, anthropometric, physical condition and dietary predictor variables were collected. A binary logistic regression was performed determining crude and adjusted Odds Ratio (OR) values, ROC curves were obtained and cut-off values were determined, calculating the sensitivity, specificity and Youden index. RESULTS: The prevalence of overweight and obesity was 26.2% and 22.3%, respectively. Only 15.2% of school children had an optimal Mediterranean diet. The waist-height ratio (WtHR) was the predictive variable with the highest adjusted OR 7.1 (4.3-11.6) and the largest area under the curve 0.954 (0.928 0.979), from a global cut-off value to discriminate obesity of 0.507. This gave a sensitivity of 90% and specificity of 87.2%. CONCLUSIONS: The high prevalence of obesity, the low-medium adherence to the Mediterranean diet and the low physical fitness make this population a priority target for the prevention of future cardiovascular events. The WtHR has been the best anthropometric predictor of obesity, recommending its use for the diagnosis of obesity in children at the expense of body mass index. PMID- 29789166 TI - [Reflection on "Critical view and argumentation on chronic care programs in Primary and Community Care"]. PMID- 29789167 TI - Prevalence of malnutrition and impact on clinical outcomes in cancer services: A comparison of two time points. AB - BACKGROUND: The prevention and management of malnutrition is increasingly recognised as a significant element of cancer care. By identifying and comparing cancer malnutrition in two large cross-sectional cancer populations, this study aims to provide a greater understanding of clinical characteristics and trajectories relating to cancer malnutrition. METHODS: A multi-centre point prevalence study was conducted in Victoria, Australia at two time points (March 2012, May 2014). Adults with cancer receiving ambulatory chemotherapy, radiotherapy and multi-day inpatients were included. The presence of malnutrition was determined using Patient Generated-Subjective Global Assessment (PG-SGA). Demographic, clinical information and 30-day outcomes were collected. RESULTS: The study included 1677 patients in 2012 (17 sites) and 1913 patients in 2014 (27 sites). Older age, >=5% weight loss, hospital admission and metastatic disease were factors significantly associated with malnutrition. Patients with upper gastrointestinal, head and neck and lung cancers were more likely to be malnourished. Malnutrition was associated with infection and poor outcomes at 30 days. Malnutrition prevalence reduced from 31% in 2012 to 26% in 2014 (p = 0.002). This reflects a reduction in patients with malnutrition receiving ambulatory chemotherapy, those with upper gastrointestinal or colorectal cancers and those residing in regional areas. CONCLUSION: The study has provided a comprehensive description of cancer malnutrition prevalence representative of all treatment settings, tumour types and stages of disease. This provides valuable insight into cancer malnutrition enabling oncology services to identify opportunities to embed identification and prevention strategies into models of care, resulting in improved patient outcomes and reduced health care costs. PMID- 29789168 TI - quanTLC, an online open-source solution for videodensitometric quantification. AB - The image is the key feature of planar chromatography. Videodensitometry by digital image conversion is the fastest way of its evaluation. Instead of scanning single sample tracks one after the other, only few clicks are needed to convert all tracks at one go. A minimalistic software was newly developed, termed quanTLC, that allowed the quantitative evaluation of samples in few minutes. quanTLC includes important assets such as open-source, online, free of charge, intuitive to use and tailored to planar chromatography, as none of the nine existent software for image evaluation covered these aspects altogether. quanTLC supports common image file formats for chromatogram upload. All necessary steps were included, i.e., videodensitogram extraction, preprocessing, automatic peak integration, calibration, statistical data analysis, reporting and data export. The default options for each step are suitable for most analyses while still being tunable, if needed. A one-minute video was recorded to serve as user manual. The software capabilities are shown on the example of a lipophilic dye mixture separation. The quantitative results were verified by comparison with those obtained by commercial videodensitometry software and opto-mechanical slit scanning densitometry. The data can be exported at each step to be processed in further software, if required. The code was released open-source to be exploited even further. The software itself is online useable without installation and directly accessible at http://shinyapps.ernaehrung.uni-giessen.de/quanTLC. PMID- 29789169 TI - Determination of organochlorine compounds in fish liver by ultrasound-assisted dispersive liquid-liquid microextraction based on solidification of organic droplet coupled with gas chromatography-electron capture detection. AB - A simple and rapid method for the extraction of organochlorine compounds (OCs) including poly-chlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in fish liver using ultrasound assisted dispersive liquid-liquid microextraction based on the solidification of floating organic droplet (US-DLLME-SFO) was developed. For reducing the complexity of the matrix, the sample was pre-treated prior to microextraction. Factors affecting US-DLLME-SFO were optimized by using statistical design of experiment (DoE). The analysis was carried out by Gas Chromatography (GC) equipped with micro electron capture detector (MU-ECD). The optimized parameters were 4.8 min of ultrasound, 3.0 mL of Milli-Q and 24 MUL of 1-undecanol as an extraction solvent as determined by DoE. US-DLLME-SFO was validated in terms of limit of detection, limit of quantification, dynamic linearity range, coefficient of determination (linearity) and extraction recovery in fish liver for OCs, and the respective values were (1.06-3.84 ng g-1), (3.50 12.67 ng g-1), (1.0-500 ng g-1), (R2 = 0.994-0.999), (88.5-108.4%). Interday and intraday precisions were evaluated as relative standard deviation (% RSD) and the values were <=10%. PMID- 29789170 TI - Method selectivity evaluation using the co-feature ratio in LC/MS metabolomics: Comparison of HILIC stationary phase performance for the analysis of plasma, urine and cell extracts. AB - Evaluation of the chromatographic separation in metabolomics studies has primarily been done using preselected sets of standards or by counting the number of detected features. An alternative approach is to calculate each feature's co feature ratio, which is a combined selectivity measurement for the separation (i.e. extent of co-elution) and the MS-signal (i.e. adduct formation and in source fragmentation). The aim of this study was to demonstrate how the selectivity of different HILIC stationary phases can be evaluated using the co feature ratio approach. The study was based on three sample types; plasma, urine and cell extracts. Samples were analyzed on an UHPLC-ESI-Q-ToF system using an amide, a bare silica and a sulfobetaine stationary phase. For each feature, a co feature ratio was calculated and used for multivariate analysis of the selectivity differences between the three stationary phases. Unsupervised PCA models indicated that the co-feature ratios were highly dependent on type of stationary phase. For several metabolites a 15-30 fold difference in the co feature ratio were observed between the stationary phases. Observed selectivity differences related primarily to the retention patterns of unwanted matrix components such as inorganic salts (detected as salt clusters), glycerophospholipids, and polyethylene glycols. These matrix components affected the signal intensity of co-eluting metabolites by interfering with the ionization efficiency and/or their adduct formation. Furthermore, the retention pattern of these matrix components had huge influence on the number of detected features. The co-feature ratio approach has successfully been applied for evaluation of the selectivity performance of three HILIC stationary phases. The co-feature ratio could therefore be used in metabolomics for developing selective methods fit for their purpose, thereby avoiding generic analytical approaches, which are often biased, as type and amount of interfering matrix components are metabolome dependent. PMID- 29789172 TI - The Role of the Pulmonologist in a Pulmonary Embolism Response Team (PERT): A Time to Come on Stage. PMID- 29789171 TI - N-Propyl-N'-2-pyridylurea-modified silica as mixed-mode stationary phase with moderate weak anion exchange capacity and pH-dependent surface charge reversal. AB - Herein, we present a novel silica-based stationary phase modified with N-propyl N'-2-pyridylurea selector. Due to the weakly basic properties of the pyridine selector and the presence of residual silanols after selector immobilization, a zwitterionic surface with a pI observed at approximately pH 5.5 was measured by electrophoretic light scattering in pH-dependent zeta-potential determinations. The capability of the new N-propyl-N'-2-pyridylurea-modified silica to serve as mixed-mode stationary phase was investigated. For this purpose, it was characterized under RP and HILIC conditions using test mixtures. Subsequent classification of this stationary phase in comparison to in-house and commercial benchmarks was carried by principal component analysis of resultant retention factors from chromatographic tests. The results show a relatively unique mixed mode character amongst the tested stationary phases. The chromatographic retention characteristics of acidic compounds matched well the zeta-potential determinations. The application of anion-exchange at low pH values (e.g. pH 5) and ion exclusion chromatography at pH 7 for the separation of uridine 5'-mono-, di- and triphosphate demonstrated a pH-dependent umpolung of the stationary phase surface. The combination of these separation principles in a pH gradient from 5 to 7 gave rise to weak anion-exchange selectivity with a charge-inducted elution due to repulsive interactions at higher pH and resulted in a significant faster separation with improved peak shape under mild elution conditions. PMID- 29789173 TI - The Exacerbation Conundrum. PMID- 29789174 TI - Pulmonary Foreign Body Granulomatosis 11 Years After Injection of a Cosmetic Dermal Filler. PMID- 29789175 TI - Macrolide Resistance in Cases of Community-Acquired Bacterial Pneumonia in the Emergency Department. AB - BACKGROUND: Emergency physicians are under pressure to prescribe an antibiotic early in the treatment course of a patient with community-acquired pneumonia (CAP). Macrolides are recommended first-line empirical therapy for the outpatient treatment of CAP in patients without associated comorbidities; however, resistance rates to macrolides in the United States are on the rise. OBJECTIVE: This review considers macrolide use for CAP in the emergency department by reviewing the microbiologic environment in the United States and whether macrolides can overcome in vitro resistance during actual clinical use. Alternatives to macrolides for CAP are briefly discussed. DISCUSSION: Resistance to macrolides is now above 25% in all regions of the United States, and resistance to other antibiotics is also on the rise. The failure of outpatient macrolide treatment for CAP because of resistance rates increases the burden of the disease both in terms of the patient and health economics. No definitive answer is available on whether macrolides will achieve treatment success despite infection with in vitro resistant strains. When selecting a therapy, a balance needs to be struck between spectrum of activity targeted against the probable etiology (including atypical pathogens) for respiratory tract infections and the need for first-time success. CONCLUSIONS: Currently available macrolides are now facing resistance rates that cloud their recommendation as a first-line treatment for CAP. Clinicians need a better understanding of their own local resistance rates, while hospitals need to do a better job in describing low- and high-level resistance rates to better inform their physicians. PMID- 29789176 TI - How to support cancer genetics counselees in informing at-risk relatives? Lessons from a randomized controlled trial. AB - OBJECTIVE: In hereditary and familial cancer, counselees are requested to inform their at-risk relatives. We developed an intervention to support counselees in this task. METHODS: A randomized controlled trial was conducted aimed at improving cancer genetic counselees' i) knowledge, ii) motivation to disclose information, and ii) self-efficacy in this regard. Eligible participants were randomized to telephonic counseling (n = 148), or standard care (n = 157) and assessed at baseline, 1 week post-intervention, and 4 months after study enrolment. RESULTS: No between-group differences were found in participants' knowledge, motivation, and self-efficacy. Knowledge concerning which second degree relatives to inform was lower compared to first-degree relatives. About 60% of the participants was of the opinion that they needed to inform more relatives than stated in their summary letter and only about 50% were correctly aware of which information to disclose. Of note, at baseline, almost 80% of the participants had already correctly informed their at-risk relatives. CONCLUSIONS: Since, unexpectedly, counselees already informed most of their relatives before the intervention was offered, efficacy of the intervention could not convincingly be determined. Counselees' knowledge about whom to inform about what is suboptimal. PRACTICE IMPLICATIONS: Future interventions should target a more homogeneous sample and address counselees' understanding and recall. PMID- 29789177 TI - Hematuria as the only symptom at initial presentation of hypovolemic shock caused by ruptured renal arteriovenous malformations. AB - Gross hematuria is a very common complaint in emergency departments and outpatient clinics. Globally, the incidence of hematuria is 4 per 1000 patients per year. Infection, urolithiasis, and neoplasm are the most common etiologies. However, hematuria rarely causes hypovolemic shock or an emergent, life threatening condition at the initial presentation. In this report, we describe the case of a 64-year-old man who suffered a life-threatening gross hematuria in a very short time due to ruptured renal arteriovenous malformations (AVMs). PMID- 29789178 TI - Corrigendum to "Double Opposing Zplasty with VY Advancement of the Perineum: Long term results of a new technique as an alternative to Fenton's operation for narrowing and splitting of the skin at the posterior vaginal fourchette" [Eur. J. Obstet. Gynecol. Reprod. Biol. 223 (2018) 46-49]. PMID- 29789179 TI - Implementation of molecular techniques for diagnosis of mumps. PMID- 29789180 TI - Epidemiology of tuberculosis in Spain: Areas of improvement in epidemiological surveillance and contributions from the Spanish Network for the Study of Pediatric Tuberculosis. PMID- 29789181 TI - Onychomycosis caused by algae without chlorophyll. PMID- 29789182 TI - Geodermatophilus chilensis sp. nov., from soil of the Yungay core-region of the Atacama Desert, Chile. AB - A polyphasic study was undertaken to establish the taxonomic status of three representative Geodermatophilus strains isolated from an extreme hyper-arid Atacama Desert soil. The strains, isolates B12T, B20 and B25, were found to have chemotaxonomic and morphological properties characteristic of the genus Geodermatophilus. The isolates shared a broad range of chemotaxonomic, cultural and physiological features, formed a well-supported branch in the Geodermatophilus 16S rRNA gene tree in which they were most closely associated with the type strain of Geodermatophilus obscurus. They were distinguished from the latter by BOX-PCR fingerprint patterns and by chemotaxonomic and other phenotypic properties. Average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between the whole genome sequences of isolate B12T and G. obscurus DSM 43160T were 89.28%, 87.27% and 37.4%, respectively, metrics consistent with its classification as a separate species. On the basis of these data, it is proposed that the isolates be assigned to the genus Geodermatophilus as Geodermatophilus chilensis sp. nov. with isolate B12T (CECT 9483T=NCIMB 15089T) as the type strain. Analysis of the whole genome sequence of G. chilensis B12T with 5341 open reading frames and a genome size of 5.5Mb highlighted genes and gene clusters that encode for properties relevant to its adaptation to extreme environmental conditions prevalent in extreme hyper arid Atacama Desert soils. PMID- 29789184 TI - Infused cardioplegia index: A new tool to improve myocardial protection. A cohort study. AB - BACKGROUND: Strategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. DESIGN: All patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. RESULTS: Of 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI=1.18-2.55]), left ventricle ejection fraction (OR 0.95 (95% CI=0.93-0.98]), ICI (OR 0.99 [95% CI=0.991-0.996]) and retrograde cardioplegia (OR 1.2 [95% CI=1.03-1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70-0.83; P<.001) for the absence of postoperative low cardiac output syndrome using the optimum cut-off point of 23.6ml.min-1(100g/m2 of LV)-1. CONCLUSIONS: The infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimising cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualised, adjusting for ischemia time and left ventricle mass index. PMID- 29789183 TI - "Do not do" recommendations of the working groups of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of critically ill patients. AB - The project "Commitment to Quality of Scientific Societies", promoted since 2013 by the Spanish Ministry of Health, seeks to reduce unnecessary health interventions that have not proven effective, have little or doubtful effectiveness, or are not cost-effective. The objective is to establish the "do not do" recommendations for the management of critically ill patients. A panel of experts from the 13 working groups (WGs) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) was selected and nominated by virtue of clinical expertise and/or scientific experience to carry out the recommendations. Available scientific literature in the management of adult critically ill patients from 2000 to 2017 was extracted. The clinical evidence was discussed and summarized by the experts in the course of consensus finding of each WG, and was finally approved by the WGs after an extensive internal review process carried out during the first semester of 2017. A total of 65 recommendations were developed, of which 5 corresponded to each of the 13 WGs. These recommendations are based on the opinion of experts and scientific knowledge, and aim to reduce those treatments or procedures that do not add value to the care process; avoid the exposure of critical patients to potential risks; and improve the adequacy of health resources. PMID- 29789185 TI - Variation in post-thaw sperm quality of white-tailed deer bucks (Odocoileus virginianus) during rut. AB - White-tailed deer farming is a growing industry in the United States, with breeding operations contributing significantly to the industry's economic impact. Artificial insemination with frozen semen allows for selection and dissemination of valuable genetics, yet surprisingly little is known regarding the best time throughout rut to perform semen cryopreservation. The objective of this study was to compare semen quality following cryopreservation of white-tailed deer bucks collected early in the breeding season (September, n = 6), at peak rut (December, n = 8), and late season (March, n = 7). We hypothesized that post-thaw semen quality would be enhanced at peak rut. Mature bucks were anesthetized with tiletamine-zolazepam and xylazine administered intramuscularly via projector. Semen was collected by electroejaculation and cryopreserved using Optixcell extender. Overall and progressive sperm motilities were assessed for each sample before and after cryopreservation using a computer-aided sperm analyzer. Flow cytometry was used for post-thaw assessment of sperm viability (SYBR-14/PI), acrosome integrity (FITC-PNA/PI), and DNA stability (acridine orange). Analysis of variance was applied to normalized data using a general linear mixed model with buck ID as a random variable, and a Tukey HSD test was performed as needed for post-hoc analysis. Pre-freeze overall and progressive sperm motilities were lowest in March, intermediate in September, and highest in December (p <= 0.04). Post-thaw overall and progressive motilities were lowest in September (p <= 0.02), but did not differ between December and March (p >= 0.12). The DNA Fragmentation Index was lowest in December, intermediate in September, and highest in March (p <= 0.05). The percentage of spermatozoa with intact plasma membrane was higher in December than September (p < 0.01), but the percentage of intact acrosomes per sperm with intact plasma membrane was highest in September (p = 0.03). This study confirms that post-thaw semen quality appears to be superior during peak rut (December) in bucks. Though semen collected early or late in rut may present acceptable motility, DNA stability is impaired, which could adversely affect fertility rates. This data suggests that semen cryopreservation during transitional periods should be avoided, though field studies evaluating the translation of these results into satisfactory pregnancy rates are warranted. PMID- 29789186 TI - A Population-Based Assessment of Depression and Anxiety in Patients With Brachial Plexus Injuries. AB - PURPOSE: Reactive depression and anxiety are common after major life changes such as brachial plexus injuries (BPI). The purpose of this study was to evaluate the incidence and risk factors for coded depression and coded anxiety among patients with BPI using a national database of commercial insurance claims. METHODS: We used the Truven MarketScan database from 2007 to 2013 to identify commercially insured patients aged 18 to 64 years who underwent BPI surgery. For comparison, a control group without BPI was frequency-matched 10:1 by age group, sex, number of provider visits, and length of insurance enrollment. Using International Classification of Diseases, Ninth Revision diagnosis codes and pharmacy claims, we identified coded depression and coded anxiety in the 12 months before and 12 months after BPI surgery. Multivariable Cox regression models were used to determine risk factors for coded depression or coded anxiety, adjusting for known risk factors for depression or anxiety (eg, alcohol, substance abuse). RESULTS: We identified 1,843 patients with BPI and 18,430 controls. Within the 12 months preceding surgery, coded depression and coded anxiety were present in 38% and 42%, respectively, of the BPI group; both were present in 25% and either was present in 54%. The rate of new-onset/postoperatively coded depression among patients with BPI was 142.1/1,000 person-years (12%) and of new onset/postoperatively coded anxiety was 273.6/1,000 person-years (20%). Patients with BPI were significantly more likely than controls to develop new onset/postoperatively coded depression (hazard ratio = 1.3; confidence interval [CI], 1.1-1.5) and new-onset/postoperatively coded anxiety (HR = 2.1 [CI, 1.8 2.4]). CONCLUSIONS: Patients undergoing BPI surgery have a high prevalence of coded depression and coded anxiety in the 12 months before surgery and are at higher risk for developing new-onset/postoperatively coded depression and coded anxiety within 1 year after surgery. These findings can be used by BPI surgeons to inform perioperative counseling, guide emotional recovery from injury, and facilitate coordinated or colocated care with mental health professionals. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. PMID- 29789187 TI - A Review of Lymphedema for the Hand and Upper-Extremity Surgeon. AB - Secondary lymphedema of the upper limb is frequently seen in Western countries after cancer treatment (most often breast in women). It is a chronic disease that affects quality of life and functioning. In its extreme form, it may be debilitating. A review is given of the pathology, nonsurgical treatment, and surgical treatment with a protocol. PMID- 29789188 TI - Fractures after multimodality treatment of soft tissue sarcomas with isolated limb perfusion and radiation; likely to occur and hard to heal. AB - OBJECTIVES: Treatment associated fractures (TAFs) are known severe side effects after surgery and radiotherapy for soft tissue sarcoma (STS). There is no literature about TAF after multimodality treatment with isolated limb perfusion (ILP) for locally advanced STS. This study aimed to analyze predictive factors, treatment and outcome for TAF after multimodality treatment with ILP. METHOD: Out of 126 consecutive patients undergoing ILP after 1991 till now, 25 patients were excluded due to no surgery or direct amputation at initial surgery. Therefore, 101 patients were at risk and 12 developed a TAF (12%). RESULTS: The majority of tumors was located at the upper leg and knee (N = 60), and 11 patients developed a TAF (18%) after median 28 (5-237) months. Twenty-five tumors were located at the lower leg, and 1 patient developed a TAF after 12 months (4%). No patients with a tumor at the upper extremities (N = 16) developed a TAF. Ten out of 12 patients with a fracture received adjuvant RT with a dose of 50 Gy, and a median boost dose of 18 (10-20) Gy. Predictive factors were periosteal stripping, age over 65 years at time of treatment and tumor size after ILP >=10 cm. Multivariate analysis showed periosteal stripping and tumor size after ILP >=10 cm as significant predictive factors. The majority of the fractures were treated with intramedullary nailing. Only one of 12 patients without radiotherapy reached bone union (8%). The median survival after developing TAF was 18 (1-195) months. CONCLUSION: The overall risk of TAF after multimodality treatment with ILP was relatively high with 15% at ten years. The incidence of TAF for patients with tumors located at the thigh and knee after resection with periosteal stripping and radiotherapy was even >50%. The treatment of these fractures is challenging due to the high non-union rate, requiring an extensive orthopedic oncological TAF experience. PMID- 29789191 TI - Corrigendum re: "Influence of Modified Posterior Reconstruction of the Rhabdosphincter on Early Recovery of Continence and Anastomotic Leakage Rates after Robot-Assisted Radical Prostatectomy" [Eur Urol 2011;59:72-80]. PMID- 29789189 TI - Antimicrobial Susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States Medical Centers Stratified by Infection Type: Results from the International Network for Optimal Resistance Monitoring (INFORM) Surveillance Program, 2015-2016. AB - A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for beta-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2 95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia. PMID- 29789190 TI - Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to identify MLST clade 4 Clostridium difficile isolates. AB - Clostridium difficile is the leading cause of health care-associated infections. Previous studies suggest that C. difficile MLST clade 4 strains with higher drug resistance rates constitute the major clone spreading in China. Thus development of a rapid and accurate typing method for these strains is needed to monitor the epidemiology of this clone and to guide clinical treatment. A total of 160 non duplicate C. difficile isolates recovered from three large teaching hospitals in Beijing were studied. All the 41 clade 4 C. difficile isolates clustered together on the PCA dendrogram. Spectra peak statistics revealed that five markers (2691.43Da, 2704.91Da, 2711.93Da, 3247.27Da and 3290.76Da) can easily and reliably distinguish between clade 4 and non-clade 4 isolates, with area under the curve (AUC) values of 0.991, 0.997, 0.973, 1 and 1, respectively. In conclusion, MALDI-TOF MS is a very simple and accurate method for identifying C. difficile MLST clade 4 strains. PMID- 29789192 TI - [Educational and information needs of patients under vitamin K antagonist therapy]. AB - BACKGROUND: Adverse events related to vitamin K antagonists (VKA) represent a major public health problem. Informative tools and educative program contributes to the reduction of iatrogenic risk. The purpose of our study is to assess representations and information needs of patients under VKA therapy in order to develop a suitable therapeutic education program. METHODS: Individual semi structured interviews were conducted among both long term VKA therapy patient and patients initiating VKA. The thematic analysis allowed us to explore patient's speech qualitatively and semi-quantitatively. RESULTS: The main needs in information concerned the modalities of treatment (27.6%), side effects (24.1%), precautions and management of VKA treatment (24.1%). Origin of the disease (P=0.022) and drug mechanism of action (0.012) were specially asked about by patients initiating their treatment. CONCLUSION: Patients under VKA therapy reported needs for information on both their pathology and their anticoagulant therapy. The therapeutic education approach will enable us to adapt the educational tools and messages to the needs of patients under VKA therapy. PMID- 29789194 TI - Operative technique for benign submandibular gland mass without identifying the mandibular branch of the facial nerve. AB - OBJECTIVE: The marginal mandibular branch of the facial nerve must be protected during surgery for benign diseases of submandibular gland. Methods for protecting the marginal mandibular branch include the nerve identification method and the non-identification method. METHODS: We performed submandibular gland surgery in 138 patients with benign submandibular gland diseases using the non identification method to preserve the marginal mandibular branch. In brief, the submandibular gland capsule is incised at the inferior border of the gland and detached along the gland parenchyma. The nerve is protected by this procedure without the need for identification. RESULTS: Among 138 patients who underwent this surgical procedure, only 7 patients developed transient paralysis of the lower lip. CONCLUSION: This method of resecting the submandibular gland without identifying the marginal mandibular branch is an effective procedure associated with a low incidence of transient paralysis. Moreover, no patient developed paralysis due to procedural errors. PMID- 29789193 TI - Deoxysphingolipid precursors indicate abnormal sphingolipid metabolism in individuals with primary and secondary disturbances of serine availability. AB - Patients with primary serine biosynthetic defects manifest with intellectual disability, microcephaly, ichthyosis, seizures and peripheral neuropathy. The underlying pathogenesis of peripheral neuropathy in these patients has not been elucidated, but could be related to a decrease in the availability of certain classical sphingolipids, or to an increase in atypical sphingolipids. Here, we show that patients with primary serine deficiency have a statistically significant elevation in specific atypical sphingolipids, namely deoxydihydroceramides of 18-22 carbons in acyl length. We also show that patients with aberrant plasma serine and alanine levels secondary to mitochondrial disorders also display peripheral neuropathy along with similar elevations of atypical sphingolipids. We hypothesize that the etiology of peripheral neuropathy in patients with primary mitochondrial disorders is related to this elevation of deoxysphingolipids, in turn caused by increased availability of alanine and decreased availability of serine. These findings could have important therapeutic implications for the management of these patients. PMID- 29789195 TI - Steroid pulse therapy transiently destroys the discriminative histological structure of tonsils in IgA nephropathy: Tonsillectomy should be performed before or just after steroid pulse therapy. AB - OBJECTIVE: Tonsillectomy combined with steroid-pulse therapy is a widely accepted method for the treatment of IgA nephropathy (IgAN) in Japan. However, the indication of tonsillectomy for IgAN is still controversial, and the timing of tonsillectomy is not clearly defined for the protocol of this therapy. Based on the results of a randomized control trial in Japan, the Evidence-Based Clinical Practice Guidelines for IgA nephropathy 2014 (edited in Japan) recommended tonsillectomy combined with steroid-pulse therapy for Grade C1. However, this is not widely accepted worldwide. To clarify the validity and timing of tonsillectomy, we evaluated how the three-consecutive steroid-pulse therapy method affects the tonsil tissues of IgAN patients. METHODS: We examined tonsil specimens from 35 IgAN patients and 8 chronic tonsillitis patients. We compared the proportion of follicular area to total tonsillar area and the number of germinal centers between each group on hematoxylin and eosin stained pathological specimens to clarify the histopathological characteristics of tonsils from IgAN patients. Based on these findings, we examined the tonsils of patients after three-consecutive steroid-pulse therapy treatments (n=34) to determine the influence of this therapy on the tonsil tissues of IgAN patients. Moreover, we observed chronological changes in tonsil tissues after steroid-pulse therapy. RESULTS: The extrafollicular area was enlarged in IgAN patients before steroid pulse therapy compared with chronic tonsillitis patients. Just after steroid pulse therapy, the follicles became very small with blurry outlines, and the number of germinal centers was remarkably decreased. With a gradual decrease in oral prednisolone, the tonsil tissue structure was gradually restored. CONCLUSION: Tonsillectomy combined with steroid-pulse therapy is considered a reasonable treatment for IgAN. Steroid-pulse therapy-induced histological changes in tonsils were transient, indicating tonsillectomy should be performed before or just after steroid-pulse therapy. PMID- 29789196 TI - Understanding and Manipulating Viral Immunity: Antibody Immunodominance Enters Center Stage. AB - Adaptive immune responses against antigenically variable viruses and cellular pathogens are efficient in many cases, but largely limited to the infecting or immunizing strain. A major factor that limits immunity is immunodominance (ID), the hierarchical focusing of adaptive immune responses on a subset of antigenic determinants. While CD8+ T cell ID has been extensively studied, studies of basic mechanisms of B cell ID are limited, despite the importance of antibodies (Abs) for durable protection against pathogens. Here, we review recent progress in understanding the basic rules and mechanisms of B cell ID, compare B and CD8+ T cell ID, and outline challenges to overcoming ID to develop Ab-based 'universal' vaccines for influenza A and other highly variable viruses. PMID- 29789197 TI - Re: Postoperative nausea and vomiting in facial fracture patients: a randomized and controlled trial on the effect of dexamethasone. PMID- 29789198 TI - Corseting: a new technique for the management of diffuse venous malformations in the head and neck region. AB - A new surgical technique of intra-tumoural ligation for the treatment of low-flow vascular malformations in the head and neck region is proposed. Ninety patients with diffuse low-flow vascular malformations diagnosed clinically and/or radiologically were treated surgically with the corset suturing technique. All patient records and clinical photographs were reviewed retrospectively. Significant clinical results were obtained: a reduction of the turnout tumour mass and a return of the regional facial outline was evident within 4 weeks after surgery. Recurrence of the lesion (seen in 10 patients) and transient facial nerve palsy (seen in seven patients) were the main complications. All incisions were placed within the junction lines of cosmetic subunits and skin tension lines of the head and neck. The advantages of this technique over the widely used and popular Popescu technique are discussed. Also, the indications, disadvantages, operative technique, and complications are described. In conclusion, corset suturing was found to be a simple, aesthetic, and cost-effective method of treating diffuse low-flow vascular malformations of the head and neck. PMID- 29789200 TI - Determination of spatial dose distribution in UCC treatments with LDR brachytherapy using Monte Carlo methods. AB - Using Monte Carlos methods, with the MCNP5 code, a gynecological phantom and a vaginal cylinder were modeled. The spatial distribution of absorbed dose rates in Uterine Cervical Cancer treatment through low dose rate brachytherapy was determined. A liquid water gynecology computational phantom, including a vaginal cylinder applicator made of Lucite, was designed. The applicator has a linear array of four radioactive sources of Cesium 137. Around the vaginal cylinder, 13 water spherical cells of 0.5 cm-diameter were modeled to calculate absorbed dose emulating the procedure made by the treatment planning system. The gamma-ray fluence distribution was estimated, as well as the absorbed doses resulting approximately symmetrical for cells located at upper and lower of vaginal cylinder. Obtained results allow the use of the radioactive decay law to determine dose rate for Uterine Cervical Cancer using low dose rate brachytherapy. PMID- 29789201 TI - Combined deletion of the fibronectin-type III domains and the stalk region results in ligand-independent, constitutive activation of the Interleukin 6 signal-transducing receptor gp130. AB - Gp130 is the common receptor within the Interleukin 6 cytokine family. Gp130 consists of 6 extracellular domains followed by a small stalk region connecting the last extracellular domain with the trans-membrane domain. Whereas the first three extracellular domains bind to IL-6-type cytokines, the domains 4-6 are needed for correct positioning of the intracellular domains to facilitate Janus kinase activation after cytokine binding. Interestingly, deletion within the cytokine-binding domain resulted in cytokine-independent constitutive activation of mutant gp130 receptors. Here, we tested the hypothesis, if deletions of the stalk region and/or domains 4-6 of gp130 might also result in constitutive receptor activation. Shortening of the stalk region of gp130 alone did, however, not result in constitutive receptor activation, whereas a gp130 receptor deletion variant only consisting of the three N-terminal cytokine binding domains but lacking all FNIII domains was biologically inactive. Importantly, combined deletion of the three FNIII domains plus shortening of the stalk region of gp130 resulted in ligand-independent, constitutive receptor activation of gp130. PMID- 29789203 TI - Papillary glioneuronal tumor. A case report. AB - Papillary glioneuronal tumor (PGNT) is a recently described central nervous system neoplasm. In 2007, the World Health Organization classified this tumor as a grade I neuronal-glial neoplasm. Patients are usually juvenile and young adults who commonly present with headache or seizures. We report a case of a 13-year-old boy that was related to our hospital after suffering a mild head injury result of an automobile accident. Emergent CT scan showed a right hypointense temporo occipital lesion. MRI confirmed the presence of a lesion suggestive of a primary brain tumor. The patient underwent total resection of the tumor, followed by an uneventful recovery. Pathological analysis of the lesion revealed characteristic pseudopapillary structure with astrocytes and neurons, compatible with PGNT. We discuss the clinical, Radiological and histological features of this infrequent type of tumors. PMID- 29789202 TI - Relationship between prolonged neural suppression and cerebral hemodynamic dysfunction during hypothermia in asphyxiated piglets. AB - OBJECTIVES: Hypothermia (HT) improves the outcome of neonatal hypoxic-ischemic encephalopathy. Here, we investigated changes during HT in cortical electrical activity using amplitude-integrated electroencephalography (aEEG) and in cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation using near-infrared time-resolved spectroscopy (TRS) and compared the results with those obtained during normothermia (NT) after a hypoxic-ischemic (HI) insult in a piglet model of asphyxia. We previously reported that a greater increase in CBV can indicate greater pressure-passive cerebral perfusion due to more severe brain injury and correlates with prolonged neural suppression during NT. We hypothesized that when energy metabolism is suppressed during HT, the cerebral hemodynamics of brains with severe injury would be suppressed to a greater extent, resulting in a greater decrease in CBV during HT that would correlate with prolonged neural suppression after insult. METHODS: Twenty-six piglets were divided into four groups: control with NT (C-NT, n = 3), control with HT (C-HT, n = 3), HI insult with NT (HI-NT, n = 10), and HI insult with HT (HI-HT, n = 10). TRS and aEEG were performed in all groups until 24 h after the insult. Piglets in the HI-HT group were maintained in a hypothermic state for 24 h after the insult. RESULTS: There was a positive linear correlation between changes in CBV at 1, 3, 6, and 12 h after the insult and low-amplitude aEEG (<5 uV) duration after insult in the HI NT group, but a negative linear correlation between these two parameters at 6 and 12 h after the insult in the HI-HT group. The aEEG background score and low amplitude EEG duration after the insult did not differ between these two groups. DISCUSSION AND CONCLUSION: A longer low-amplitude EEG duration after insult was associated with a greater CBV decrease during HT in the HI-HT group, suggesting that brains with more severe neural suppression could be more prone to HT-induced suppression of cerebral metabolism and circulation. PMID- 29789204 TI - Quantification of the omega5- and gamma-gliadin content in wheat flour and rat plasma with an enzyme-linked immunosorbent assay using antibodies specific to their IgE-binding epitopes. PMID- 29789199 TI - Survival after in-hospital cardiac arrest among cerebrovascular disease patients. AB - Stroke is a leading cause of death and disability, and while preferences for cardiopulmonary resuscitation (CPR) are frequently discussed, there is limited evidence detailing outcomes after CPR among acute cerebrovascular neurology (inclusive of stroke, subarachnoid hemorrhage (SAH)) patients. Systematic review and meta-analysis of PubMed and Cochrane libraries from January 1990 to December 2016 was conducted among stroke patients undergoing in-hospital CPR. Primary data from studies meeting inclusion criteria at two levels were extracted: 1) studies reporting survival to hospital discharge after CPR with cerebrovascular primary admitting diagnosis, and 2) studies reporting survival to hospital discharge after CPR with cerebrovascular comorbidity. Meta-analysis generated weighted, pooled survival estimates for each population. Of 818 articles screened, there were 176 articles (22%) that underwent full review. Three articles met primary inclusion criteria, with an estimated 8% (95% Confidence Interval (CI) 0.01, 0.14) rate of survival to hospital discharge from a pooled sample of 561 cerebrovascular patients after in-hospital CPR. Twenty articles met secondary inclusion criteria, listing a cerebrovascular comorbidity, with an estimated rate of survival to hospital discharge of 16% (95% CI 0.14, 0.19). All studies demonstrated wide variability in adherence to Utstein guidelines, and neurological outcomes were detailed in only 6 (26%) studies. Among the few studies reporting survival to hospital discharge after CPR among acute cerebrovascular patients, survival is lower than general inpatient populations. These findings synthesize the limited empirical basis for discussions about resuscitation among stroke patients, and highlight the need for more disease stratified reporting of outcomes after inpatient CPR. PMID- 29789205 TI - Genetic variants related to urate and risk of Parkinson's disease. AB - INTRODUCTION: Higher urate concentrations have been associated with a lower risk of developing Parkinson's disease (PD) and with slower rates of clinical decline in PD patients. Whether these associations reflect a neuroprotective effect of urate is unclear. Our objective was to assess whether genetic variants that modify circulating urate levels are also associated with altered PD risk. METHODS: Participants were from three large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Cancer Prevention Study II Nutrition Cohort (CPS-IIN). We examined associations between single nucleotide polymorphisms (SNPs) in SLC2A9 and other genes involved in urate transport and PD risk using conditional logistic regression among 1451 cases and 3135 matched controls. We assessed associations between SNPs and plasma urate levels in a subset of 1174 control participants with linear regression models. RESULTS: We found the expected associations between SNPs in SLC2A9 and plasma urate levels among men and women; however, SNPs in other genes tended not to be associated with urate. Each SNP in SLC2A9 explained less than 7% of the variance in plasma urate. We did not find significant associations between the SNPs in SLC2A9 and PD risk among men or women. CONCLUSION: Our results do not support an association between genetic variants associated with circulating urate levels and risk of PD, but larger investigations are needed to determine whether the modest genetic effects on blood urate contribute to predict PD risk. PMID- 29789206 TI - Environmental Signals Influencing Myeloid Cell Metabolism and Function in Diabetes. AB - The environment induces metabolic reprogramming of immune cells via specific signaling pathways. Recent studies have revealed that changes in cell metabolism affect key immune cell functions including cytokine production and migration. In diabetes, these functions are either insufficiently or excessively activated, translating into diabetes-associated complications, including increased susceptibility to infection and accelerated cardiovascular disease. Diabetes alters the abundance of environmental signals, including glucose, insulin, and lipids. Subsequently, changes in environmental signals drive metabolic reprogramming, impair immune cell function, and ultimately contribute to diabetes associated complications. We review here recent studies on changes in innate immune cell metabolism, especially in myeloid cells, that are driven by environmental signals relevant to diabetes, and discuss therapeutic perspectives of targeting metabolism of immune cells in diabetes. PMID- 29789207 TI - Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair. AB - Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on alpha-amylase and significant activity on alpha-glucosidase; however malabaricone B (6) and C (7) were identified as potent alpha-glucosidase inhibitors with IC50 values of 63.70 +/- 0.546, and 43.61 +/- 0.620 uM respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2 deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus. PMID- 29789208 TI - Synthesis of 4'-C-aminoalkyl-2'-O-methyl modified RNA and their biological properties. AB - In this paper, we describe the synthesis of 4'-C-aminoalkyl-2'-O methylnucleosides and the properties of RNAs containing these analogs. Phosphoramidites of 4'-C-aminoethyl and 4'-C-aminopropyl-2'-O-methyluridines were prepared using glucose as starting material, and RNAs containing the analogs were synthesized using the phosphoramidites. Thermal denaturation studies revealed that these nucleoside analogs decreased the thermal stabilities of double stranded RNAs (dsRNAs). Results of NMR, molecular modeling, and CD spectra measurements suggested that 4'-C-aminoalkyl-2'-O-methyluridine adopts an C2'-endo sugar puckering in dsRNA. The 4'-C-aminoalkyl modifications in the passenger strand and the guide strand outside the seed region were well tolerated for RNAi activity of siRNAs. Single-stranded RNAs (ssRNAs) and siRNAs containing the 4'-C aminoethyl and 4'-C-aminopropyl analogs showed high stability in buffer containing bovine serum. Thus, siRNAs containing the 4'-C-aminoethyl and 4'-C aminopropyl analogs are good candidates for the development of therapeutic siRNA molecules. PMID- 29789209 TI - All is not lost: Post-saccadic contributions to the perceptual omission of intra saccadic streaks. AB - Saccades rapidly jerk the eye into new positions, yet we rarely experience the motion streaks imposed on the retinal image. Here we examined spatial and temporal properties of post-saccadic masking-one potential explanation of this perceptual omission. Observers judged the motion direction of a target stimulus, a Gaussian blob, that moved vertically upwards or downwards and then back to its initial position, just as observers made a saccade. We manipulated the onset and offset of the target and of distractors in various spatial relations to the target, and assessed their effect on performance and subjective confidence. Although the presence of the target after the saccade caused the strongest omission, the offset of spatially distant distractor stimuli upon saccade offset also impaired performance. The temporal properties of these two separate effects suggest that, in addition to masking, an independent effect of attentional distraction further accentuates perceptual omission of intra-saccadic motion streaks. PMID- 29789210 TI - Should first blood pressure measurement be performed in the newborn? AB - Dilated cardiomyopathy is the most common form of cardiomyopathy and the main cause of cardiac transplantation in children and in adults. Infants and children have a wider spectrum of etiologies, hampering their identification. The most frequent initial manifestation of dilated cardiomyopathy is symptomatic heart failure during exercise or at rest (although many patients are asymptomatic). Some causes are potentially reversible, therefore the investigation should be carefully planned and immediately performed after diagnosis. In most children no cause is identified, which limits the targeted therapeutic approach and therefore the effectiveness of the treatment. The authors present a case of dilated cardiomyopathy secondary to renovascular hypertension diagnosed in an infant with 3.5 month-old, highlighting the etiological investigation, treatment and evolution. The authors present this case emphasising the fact that the arterial hypertension diagnose in infants is not always easy, questioning the current recommendations relating to an initial evaluation on blood pressure. We postulate that the assessment of blood pressure in newborns can detect early renovascular hypertension (and even other cardiovascular diseases) and help prevent the development of deleterious effects, including fatal episodes. PMID- 29789211 TI - Distress thermometer for preoperative screening of patients with oral squamous cell carcinoma. AB - In this study, we evaluate the association between distress, various demographic and medical variables, and the prevalence of psychosocial distress in preoperative patients with oral squamous cell carcinoma. A total of 100 consecutive patients were recruited into the study and asked to complete the Distress Thermometer (DT) form with the Problem List questionnaire prior to surgical intervention; the average distress score was 5.7 +/- 2.7. The distress score was neither correlated with age (r = -0.025; p = 0.804) nor with tumor size (r = 0.028; p = 0.785). General worries, anxiety, sadness, depression, pain, exhaustion, sleeping disorders, or problems with nutrition resulted in significantly higher distress scores compared to patients without these complaints. Individuals with a DT score of 5 or higher (p = 0.006) were advised to seek out psychological support. There is a strong correlation between a high DT score and emotional disorders, as well as physical problems. PMID- 29789213 TI - Severe hypertriglyceridemia. Clinical characteristics and therapeutic management. AB - INTRODUCTION: The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. OBJECTIVES: The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. METHODS: A cross-sectional study was carried out using the computerised medical records of all patients>18 years of age with a blood triglyceride level>=1,000mg/dL between 1 January 2011 and 31 December 2016. Clinical and laboratory variables were collected. The behaviour of the physicians in the 6 months after the lipid finding was analysed. RESULTS: A total of 420 patients were included (mean age 49.1+/-11.4 years, males 78.8%). The median of triglycerides was 1,329mg/dL (interquartile range 1,174-1,658). No secondary causes were found in 34.1% of the patients. The most frequent secondary causes were obesity (38.6%) and diabetes (28.1%). Physical activity was recommended and a nutritionist was referred to in 49.1% and 44.2% of the patients, respectively. Secondary causes were identified and attempts were made to correct them in 40.7% of cases. The most indicated pharmacological treatments were fenofibrate 200mg/day (26.5%) and gemfibrozil 900mg/day (19.3%). Few patients received the indication of omega 3 fatty acids or niacin. CONCLUSION: This study showed, for the first time in our country, the characteristics of a population with severe hypertriglyceridaemia. The therapeutic measures instituted by the physicians were insufficient. Knowing the characteristics in this particular clinical scenario could improve the current approach of these patients. PMID- 29789212 TI - Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration. AB - Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels. PMID- 29789215 TI - Clinical outcomes and influencing factors of in-stent restenosis after stenting for symptomatic stenosis of the vertebral V1 segment. AB - OBJECTIVE: The objective of this study was to evaluate 30-day and long-term clinical outcomes and influencing factors of in-stent restenosis (ISR) after stenting for symptomatic stenosis of the vertebral V1 segment. METHODS: The clinical and follow-up data of 301 consecutive patients (mean age, 64 +/- 8 years; 252 men) with symptomatic V1 stenosis who underwent stenting at the Fuwai Hospital between January 2010 and June 2016 were collected retrospectively. The 30-day and long-term follow-up of stroke and death after stenting and the recurrence of symptoms, ISR, and repeated revascularization were assessed. RESULTS: Technical success was 100%. The mean stenosis of lesions was reduced from 82.8% +/- 7.6% to 4.4% +/- 4.0% immediately after 312 stents (165 bare-metal stents [BMSs] and 147 drug-eluting stents) were implanted. The overall risk of combined any stroke and death was 1.0% (3/301) within 30 days after stenting. The rates of freedom from any stroke and death were 98.2%, 96.8%, and 91.4% at 1 year, 3 years, and 5 years, respectively. After a mean follow-up of 2.9 +/- 1.5 years, 46 (15.8%) patients developed ISR, of whom 19 (6.5%) were symptomatic. Twenty-two (7.6%) patients with ISR underwent repeated revascularization. The primary and assisted patency rates were 90.0% and 95.4%, 82.6% and 90.3%, and 80.3% and 87.9% at 1 year, 3 years, and 5 years, respectively. BMS (hazard ratio, 2.02; 95% confidence interval, 1.01-4.06; P < .05) and diabetes (hazard ratio, 1.87; 95% confidence interval, 1.04-3.37; P = .04) were independently associated with an increased risk of ISR. CONCLUSIONS: Percutaneous stent placement for symptomatic V1 stenosis is safe and associated with a good long-term patency rate. BMS and diabetes are independent predictive factors of ISR. PMID- 29789214 TI - Emergent carotid endarterectomy versus stenting in acute stroke patients with tandem occlusion. AB - OBJECTIVE: Acute stroke due to tandem cervical internal carotid artery (ICA) and intracranial large-vessel occlusion (ILVO) has a high rate of morbidity and mortality. The most appropriate treatment strategy for the extracranial culprit lesion remains unclear. In this study, we report our institutional outcomes with two approaches: emergent carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: Patients with tandem ICA-ILVO were identified in a prospective mechanical thrombectomy (MT) database between July 2012 and April 2016. Patients had a concomitant complete ICA origin occlusion and occlusion of the intracranial ICA or M1 or M2 middle cerebral artery segment. Baseline characteristics, procedural data, and treatment times were reviewed. End points included good recanalization of both ICA and ILVO, symptomatic intracerebral hemorrhage (defined by clinical decline of >4 points on the National Institutes of Health Stroke Scale), and functional outcome at 90 days. RESULTS: Forty-five patients had tandem ICA-ILVO occlusion; 27 patients underwent emergent CAS and 12 patients underwent emergent CEA after MT. Successful Thrombolysis in Cerebral Infarction grade 2B/3 recanalization was achieved in 92% of the CEA and 96% of the CAS patients (P = .53). Three CAS patients (11%) and none of the CEA patients had symptomatic intracerebral hemorrhage (P = .54). At 90 days, 75% (9/12) of the CEA patients were functionally independent compared with 70% (19/27) in the CAS group (P = 1.0). No deaths were noted in the CEA group compared with five (18.5%) in the CAS arm (P = .30). CONCLUSIONS: Our study indicates that early recanalization with MT followed by emergent CEA is safe and feasible, which suggests that both CAS and CEA should be considered in the emergent treatment of patients with tandem occlusion. PMID- 29789216 TI - The clinical presentation and collateral pathway development of congenital absence of the internal carotid artery. AB - OBJECTIVE: The objective of this study was to investigate the clinical presentation, risks, and collateral pathway development of the congenital absence of the internal carotid artery (ICA). METHODS: Sixty-four patients (10 new patients and 54 patients from the relevant literature) were studied. Data on demographic, clinical, and radiologic features were collected, followed by an analysis of the risks associated with ICA agenesis. RESULTS: There were 31 male and 33 female patients whose ages ranged from 5 months to 75 years, with a mean age of 31.1 years. The range of clinical symptoms recorded included transient ischemic attack (17 patients), subarachnoid hemorrhage (12 patients), developmental delay (13 patients), asymptomatic (8 patients), and other symptoms (15 patients). All 64 patients presented with absence of unilateral or bilateral ICAs, as measured by cervical computed tomography angiography or magnetic resonance angiography. The carotid canal was absent in all patients on computed tomography of the base of the skull, and abnormal development of collateral circulation pathways was observed. Five patients presented with basilar artery dilation on angiography. Aneurysms were observed in the angiography results from 16 patients. Ten patients presented with variations in the ophthalmic artery origin (the ophthalmic artery originated from the ipsilateral middle meningeal artery in six patients and from the ipsilateral middle cerebral artery in four patients). CONCLUSIONS: From analysis of our 10 cases of ICA agenesis and our review of the relevant literature, we conclude that young patients with ICA agenesis may present with developmental delay, subarachnoid hemorrhage, or other developmental abnormalities, whereas older patients most commonly present with transient neurologic events. Complications of carotid agenesis are related to specific anatomic subtypes and the resulting collateral circulation development. PMID- 29789218 TI - Does Too Much MAGIC Lead to Mitophagy? AB - Neurodegeneration-associated hallmarks include an abundance of protein aggregates and amelioration of mitochondrial function. Despite the knowledge of molecular counteracting mechanisms, the molecular dialogue between protein aggregate accumulation and aberrant mitochondrial import is poorly understood. Recent work unraveled a novel role for the mitochondrial import machinery in regulating cytosolic proteostasis. PMID- 29789217 TI - Outcomes and cost of open versus endovascular repair of intact thoracoabdominal aortic aneurysm. AB - OBJECTIVE: Many previous studies have evaluated the outcomes of open and endovascular repair of thoracoabdominal aortic aneurysms (TAAAs). However, little is known about the differences in cost of these procedures and the potential factors driving these differences. The aim of this study was to evaluate the outcomes and cost of open aortic repair (OAR) vs endovascular repair of intact TAAA. METHODS: All patients undergoing repair for intact TAAA were identified in the Premier Healthcare Database (July 2009-March 2015). Categorical and continuous variables were analyzed using the chi2 test, Student t-test, and median test as appropriate. A multivariable generalized linear model was used to examine total in-hospital cost. RESULTS: A total of 879 TAAA repairs were identified (481 [55%) endovascular repairs vs 398 [45%] OARs). Patients undergoing endovascular repair were on average 5 years older (71.2 [+/-10.0] years vs 66.5 [+/-10.9] years; P < .001) and more likely to be female (48% vs 42%; P = .05) and hypertensive (87% vs 80%; P = .009). Otherwise, there were no significant differences in comorbidities between the two groups. Patients undergoing OAR were more likely to stay longer in the hospital (median [interquartile range], 11 [7-20] days vs 5 [2-9] days; P < .001). In-hospital mortality (15% vs 5%; P < .001) and all major complications were two to three times higher after OAR. The median total cost of OAR was significantly higher compared with endovascular repair (cost [interquartile range], $44,355 [$32,177 $54,824] vs $36,612 [$24,395-$53,554]; P = .004). The majority of the cost attributed to TAAA repair was also higher in patients undergoing open repair: room and board ($11,561 vs $4720), operating room ($9230 vs $4929), pharmacy ($2309 vs $900), blood bank ($1189 vs $195), rehabilitation/physical therapy ($378 vs $236), and respiratory therapy ($875 vs $168; all P < .001). Only the cost of central supplies, which includes endovascular grafts and stents, was the highest among patients undergoing endovascular repair ($17,472 vs $5501; P < .001). The cost of diagnostic imaging ($625 vs $595) and anesthesia ($479 vs $478) was similar in both approaches. In a multivariable analysis, the adjusted total hospitalization cost for OAR was $5974 (95% confidence interval, $1828 $10,120; P = .005) higher compared with endovascular repair. However, after adjusting for in-hospital complications, no difference was seen between the two approaches (-$460; 95% confidence interval, -$4390 to $3470; P = .82). CONCLUSIONS: In this large cohort of intact TAAAs, we showed a significantly higher adjusted total hospitalization cost of open compared with endovascular repair despite the additional cost of endografts. This is likely driven by longer length of stay and higher morbidity after OAR. PMID- 29789219 TI - Cap-Independent Translation: What's in a Name? AB - Eukaryotic translation initiation relies on the m7G cap present at the 5' end of all mRNAs. Some viral mRNAs employ alternative mechanisms of initiation based on internal ribosome entry. The 'IRES ideology' was adopted by researchers to explain the differential translation of cellular mRNAs when the cap recognition is suppressed. However, some cellular IRESs have already been challenged and others are awaiting their validation. As an alternative cap-independent mechanism, we propose adopting the concept of cap-independent translation enhancers (CITEs) for mammalian mRNAs. Unlike IRESs, CITEs can be located both within 5' and 3' UTRs and bind mRNA-recruiting translational components. The respective 5' UTRs are then inspected by the scanning machinery essentially in the same way as under cap-dependent translation. PMID- 29789220 TI - ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection. AB - INTRODUCTION: Currently, the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as adjuvant therapy for early-stage non-small-cell lung cancer after complete surgical tumor resection remains under investigation. We present the rationale and study design for the ADAURA (ClinicalTrials.gov identifier, NCT02511106) trial, a multicenter, double-blind, randomized, placebo controlled study. PATIENTS AND METHODS: Study entry will be limited to adults aged >= 18 years (and in Japan and Taiwan, age >= 20 years) with primary nonsquamous stage IB-IIIA non-small-cell lung cancer with central confirmation of an EGFR exon 19 deletion or L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily or placebo once daily until disease recurrence, a treatment discontinuation criterion is met, or patients achieve the maximum treatment duration of 3 years. The primary endpoint of this study is disease-free survival. Secondary endpoints include the disease-free survival rate at 2, 3, and 5 years, overall survival, overall survival rate at 5 years, and safety and tolerability. Health-related quality of life and pharmacokinetics will also be evaluated. The exploratory objectives include assessment of osimertinib efficacy in patients with a confirmed baseline T790M mutation status and postrecurrence outcomes, health resource use, and a comparison of plasma-derived circulating tumor DNA EGFR mutation status at baseline and at disease recurrence. RESULTS: Study enrollment began in August 2015, and results are expected in the third quarter of 2021 (depending on the actual event rate). PMID- 29789221 TI - Germline silencing of UASt depends on the piRNA pathway. PMID- 29789222 TI - Risk of metabolic syndrome in adolescents with polycystic ovarian syndrome: A systematic review and meta-analysis. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is the commonest reproductive disorder in women and is closely associated with the development of metabolic syndrome (MetS). The objective of this systematic review and meta-analysis was to describe the risk of MetS in adolescent with PCOS to help diagnosing and preventing of morbidity and mortality later in life. METHODS: Pubmed, Medline, EMBASE, CINAHL and other sources were searched for metabolic syndrome in adolescents with polycystic ovarian syndrome using PRISMA guidelines (Moher et al., 2009). All type of study design of women aged 10-20 reported association of PCOS with metabolic syndrome was included in this study. Meta-analysis was conducted for MetS and its individual component using bias adjusted quality effect model and we compare the results from quality effects with random effects and IVhet model. Data were presented as prevalence, odds ratio (95% confidence interval and mean difference (95% confidence interval). RESULTS: This systematic review included 9 studies while the meta-analysis included 7 studies. Meta analysis showed that the odds of being experiencing MetS in PCOS groups was 2.69 (1.29, 5.60) times than girls without PCOS. The mean difference between girls with PCOS and without PCOS for systolic blood pressure was 5.00 (1.28, 8.72), diastolic blood pressure was 3.50 (0.48, 6.56), triglycerides level was 4.20 ( 3.99, 12.45), glucose level was 1.30 (-0.46, 3.05), HDL level was -1.40 (-4.85, 2.00). CONCLUSION: This systematic review and meta-analysis support the hypothesis that the risk of MetS is much greater in adolescents with PCOS compared to the normal population. It is important to screen PCOS in early age to prevent MetS and its complications which lead to morbidity and mortality later in life. PMID- 29789223 TI - Vitamin D status in diabetic children and adolescents. AB - INTRODUCTION: Besides its role in calcium homeostasis, vitamin D (VD) has an important immuno-mudulation effect. However, its role in autoimmune diseases such as type 1 diabetes is under discussion. This study designed to investigate serum VD status in children and adolescents with and without diabetes. MATERIALS AND METHODS: In a case-control study, 85 diabetic and 85 non-diabetic control (total 170) aged 1-15 yr. were enrolled. History of breast feeding and vitamin supplementation was obtained; growth indices and serum levels of Calcium, phosphorous, Alkaline-Phosphatase (ALP), Hemoglobin-A1c and VD were measured and analyzed. RESULTS: The mean values for VD in case and control groups were 12.80 +/- 10.59 and 15.85 +/- 9.92 nmol/L, respectively (p = 0.057). Serum VD status in these two groups was sufficient in 5.88% and 9.41%, insufficient in 18% and 14%, and deficient in 75.29% and 76.74%, respectively. Compared to the controls, diabetics had more history of breast-feeding (62.35% vs. 42.35%; p = 0.017) and higher serum ALP levels (772.34 +/- 309.89 vs. 657.99 +/- 395.11 U/L; p = 0.032). CONCLUSION: More frequency of breast-feeding, higher serum ALP and mildly lower serum level of VD in diabetics suggests a significant difference in VD status in diabetics compared to the healthy peers indicating a potential role of this deficiency in the disease process. PMID- 29789225 TI - Grafting for bone defects after curettage of benign bone tumor - Analysis of factors influencing the bone healing. AB - BACKGROUND: Simple bone cyst often weaken bone properties and predispose to pathological fractures, requiring tumor excision and the filling of bone defects with grafts to prevent complications. The purpose of this study was to evaluate factors potentially affecting the quality and efficiency of graft healing. METHODS: This study retrospectively assessed 84 patients with simple bone cysts who had undergone tumor excision and filling of the bone defects with grafts between 2004 and 2014. Various patient-, tumor- and treatment-related factors that could potentially influence radiologic healing status and time to stable healing were evaluated. RESULTS: Bone healing was not related to gender and age. Graft type was not significantly correlated with both radiologic healing status or time to stable healing. Only two of all variables evaluated were significantly correlated with the prognosis: (1) Tumors location: patients with tumors located at proximal femur were significantly more likely to achieve complete healing (Neer I) (OR = 3.2; 95%CI, 1.29-8.00; p = 0.011). (2) Tumor length: patients with a tumor length less than 6.2 cm, complete healing was nearly five times more likely to occur (OR = 4.84; 95% CI, 1.83-12.84; p = 0.002). Degree of graft filling of the bone defects affected the time to stable healing. The average healing times were 4.86 months for filling degree >=90% and 5.94 months for filling degrees <90%, respectively (p = 0.009). Postoperative re-fracture occurred in one case. CONCLUSION: Factors influencing the quality of bone healing following intralesional curettage and bone grafting are proximal femur location and tumor length. A greater degree of graft filling can contribute to higher bone healing efficiency. PMID- 29789226 TI - Engineering E. coli to Have a Hybrid Archaeal/Bacterial Membrane. AB - Bacteria and Archaea have membrane lipids with an opposite stereochemistry. The most plausible explanation for this differentiation implies an unstable heterochiral membrane stage. A recent study engineered Escherichia coli with a significant abundance of archaeal lipids showing higher robustness, disproving heterochirality as the driving force for this differentiation. PMID- 29789228 TI - Distinct kinetics of two pathologies induced in mice by topical treatment with imiquimod cream: Psoriasis-like inflammation and systemic autoimmunity. PMID- 29789227 TI - Cost-effectiveness analysis of sensor-augmented pump therapy with low glucose suspend in patients with type 1 diabetes mellitus and high risk of hypoglycemia in Spain. AB - OBJECTIVE: To compare the cost-effectiveness of sensor-augmented pump therapy (SAP) [continuous subcutaneous insulin infusion (CSII) plus real-time continuous glucose monitoring (RT-CGM)] with low glucose suspend (MiniMedTM VeoTM) and CSII alone in patients with type 1 diabetes mellitus (T1DM) at high risk of hypoglycemia in Spain. METHODS: The IQVIA CORE Diabetes Model was used to estimate healthcare outcomes as life-years gained (LYGs) and quality-adjusted life years (QALYs), and to project lifetime costs. Information about efficacy, resource utilization, and unit costs (?2016) was taken from published sources and validated by an expert panel. Analyses were performed from both the Spanish National Health System (NHS) perspective and the societal perspective. RESULTS: From the NHS perspective, SAP with low glucose suspend was associated to a ?47,665 increase in direct healthcare costs and to increases of 0.19 LYGs and 1.88 QALYs, both discounted, which resulted in an incremental cost-effectiveness ratio (ICER) of ?25,394/QALY. From the societal perspective, SAP with low glucose suspend increased total costs (including direct and indirect healthcare costs) by ?41,036, with a resultant ICER of ?21,862/QALY. Considering the willingness-to pay threshold of ?30,000/QALY in Spain, SAP with low glucose suspend represents a cost-effective option from both the NHS and societal perspectives. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: From both the Spanish NHS perspective and the societal perspective, SAP with low glucose suspend is a cost-effective option for the treatment of T1DM patients at high risk of hypoglycemia. PMID- 29789229 TI - Cryoglobulinemic vasculitis and psoriatic arthritis: Case report of an unusual association. AB - We report the case of a 47-year-old man with a 9-year history of psoriatic arthritis (PsA) in whom we detected renal involvement, hypocomplementemia, peripheral neuropathy, acral necrotic lesions and positive cryoglobulins. The results of the diagnosis led us to conclude that the clinical picture corresponded to cryoglobulinemic vasculitis concomitant with PsA. In addition, we present a review of the literature on the presence of these two diseases in a single patient. PMID- 29789230 TI - Impact of Second-Opinion Interpretation of Breast Imaging Studies in Patients Not Currently Diagnosed With Breast Cancer. AB - PURPOSE: To study the impact of second-opinion interpretation of breast imaging studies submitted from outside facilities to a tertiary cancer center. MATERIALS AND METHODS: A retrospective database review was conducted of second-opinion interpretations rendered at our institution from January 1, 2010, to June 30, 2014, on studies from patients who did not have a concurrent breast cancer diagnosis. A total of 2,253 patients were included. RESULTS: In 800 of 2,253 patients (35.5%), the BI-RADS categories assigned at our institution and at outside facilities were discordant. Of 973 patients assigned BI-RADS category 4 or 5 at outside facilities, 278 (28.6%) were assigned BI-RADS category 1 to 3 (no biopsy necessary) at our institution. Of 923 patients assigned BI-RADS category 1 to 3 at outside facilities, 191 (20.7%) were assigned BI-RADS category 4 or 5 at our institution, and 189 of these had biopsies, which revealed 23 cancers, 15 high-risk lesions, and 151 benign lesions. One high-risk lesion at core biopsy was upgraded to invasive ductal carcinoma and ductal carcinoma in situ (DCIS) on excision, resulting in 24 cancers. Of these, 18 reflected true additional breast cancers detected as a result of second-opinion interpretation: 12 invasive carcinomas and 6 cases of DCIS. These results translate into a 9.4% (18/191) positive predictive value for the number of cancers diagnosed among all biopsies recommended and a 9.5% (18/189) positive predictive value for the number of cancers diagnosed among all biopsies recommended and actually performed. CONCLUSIONS: These findings demonstrate the positive clinical impact of second opinion interpretation at a tertiary cancer center of outside-facility breast imaging studies in patients without a breast cancer diagnosis. PMID- 29789231 TI - Assessment of Appropriate Recovery Time After Liver Biopsy. PMID- 29789232 TI - High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels. AB - PURPOSE: The aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. METHODS: This institutional review board-approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 +/- 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. RESULTS: Rate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). CONCLUSION: A higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer. PMID- 29789233 TI - Amyotrophic neuralgia of atypical presentation associated with exposure to a hepatitis B vaccine. PMID- 29789234 TI - Exploring positive surgical margins after minimally invasive radical prostatectomy: Does body habitus really make a difference ? AB - BACKGROUND: Positive surgical margins (PSMs) at radical prostatectomy (RP) are generally recognized as a surrogate of poor or difficult dissection of the prostatic gland. In open RP cohorts, obesity seems to be associated to an increased risk of PSMs, probably due to the technical challenge that obese men pose to surgical access. Minimally invasive RP has been claimed to possibly reduce PSM rate. Aim of the study was to explore the impact of obesity and body habitus on PSM risk and their localisation during laparoscopic and robotic assisted RP. MATERIALS AND METHODS: We reviewed 539 prospectively enrolled patients undergoing laparoscopic and robotic-assisted RP with pT2 prostate cancer. The outcome measured was rate of PSM according to the BMI and surgical approach (laparoscopic vs robotic-assisted). Patients were categorized in BMI<25kg/m2, BMI 25-29.9kg/m2 and BMI >30kg/m2 groups respectively and compared using Kruskall-Wallis or chi2 test, as appropriate. Uni- and multivariate logistic regression models were constructed to assess the impact of BMI and surgical technique on PSM risk. RESULTS: Overall, 127 (24%) of men had PSMs detected at final specimen evaluation. Mean PSM length was 3.9+/-3.4mm, and 30 (6%) men presented significant margins >=4mm. Analysing the rate of PSMs across BMI categories, no significant association between increased BMI and PSM was detected (all P>0.48). On uni- and multivariate logistic regression BMI was not a statistically significant risk factor for PSM (P=0.14), nor was the minimally invasive technique (laparoscopic vs robotic-assisted) (P=0.54). CONCLUSIONS: In this study obese men do not appear to have a significant increase in risk of PSMs at RP compared to lean and overweight men when operated by a minimally invasive approach. The magnified vision and increased access to the pelvis allowed by a laparoscopic and robotic-assisted approach may be accountable for our findings. Larger studies are needed to validate our results. LEVEL OF PROOF: 4. PMID- 29789235 TI - [Pathology findings after radical prostatectomy for prostate cancer in patients eligible for active surveillance: Contribution of multiparametric MRI to treatment decision]. AB - OBJECTIVES: To analyze, in patients with prostate cancer (PC) potentially eligible for active surveillance (AS), whether multiparametric-MRI (mp-MRI) predicts presence of clinically significant cancer on radical prostatectomy (RP) specimen. METHODS: We identified 77 men with PC eligible for AS (PSA<=15ng/mL, stage<=T2a, Gleason score<=6, up to 3 positive cores, maximal cancer core length<=5mm) who underwent RP between 01/2008 and 08/2015. All patients had prebiopsy mp-MRI followed by systematic+/-targeted biopsies. For each patient, the likelihood of the presence of cancer on mp-MRI was assigned using Likert scale (1 to 5). The predictive factors for the presence of significant cancer on RP specimen (Gleason score>=7 and/or tumoral maximal diameter>10mm) were evaluated using logistic regression. RESULTS: Median age was 61 and median PSA was 6.7ng/mL. Overall, 49 (64%) patients had a positive mp-MRI (score>=3). Clinically significant cancer on RP specimen was found in 45 (58%) patients (69% in MRI-positive patients vs 39% in MRI-negative patients). In multivariate analysis, a positive MRI was a predictive factor for the presence of significant cancer on the surgical specimen (OR=3.0; CI95% [1.01-8.88]; P=0.04), as was age (OR=1.17; CI95% [1.05-1.31]; P=0.004) and PSAD (OR=1.10; CI95% [1.01-1.20]; P=0.02). CONCLUSION: Mp-MRI is a useful exam for selecting patients eligible for AS even if the situation remains unclear after prostate biopsies including targeted biopsies. Upon confirmation by further studies, mp-MRI should be considered as an independent criterion before entering an AS program. LEVEL OF EVIDENCE: 4. PMID- 29789236 TI - [Study of the beneficial effects of triptorelin on lower urinary tract symptoms in Algeria in patients with non-localized prostate cancer]. AB - INTRODUCTION: This study aims to assess the effectiveness of triptorelin on lower urinary tract symptoms (LUTS) in Algerian patients with non-localized prostate cancer in routine practice. MATERIALS: This prospective, observational, non interventional, multicentre study was conducted in Algeria. Included patients who had locally advanced or metastatic prostate cancer and were treated with triptorelin 11.25mg given every 12 weeks. LUTS were evaluated with the International Prostate Symptom Score (IPSS) until week 48 after treatment initiation. An IPSS>7 indicated moderate to severe LUTS. The primary objective of the study was to determine the distribution of IPSS at week 48. RESULTS: This study enrolled 193 patients at 21 centres. A total of 144 participants had IPSS available at baseline and after baseline (136 patients had moderate to severe LUTS and eight had mild LUTS at baseline). At week 48, amongst the 116 patients with IPSS available and moderate to severe LUTS at baseline, 94 (81.0%) had moderate to severe LUTS and 22 (19.0%) had mild LUTS. At week 48, the eight patients with mild symptoms at baseline remained in this category. The proportion of patient with severe LUTS decreased from 53.7% at baseline to 12.1% at week 48. Adverse events were reported in 22.9% of participants. CONCLUSION: A reduction of LUTS is observed in patients with locally advanced or metastatic prostate cancer treated with triptorelin in routine practice. This is in agreement with similar observational studies of triptorelin conducted in other countries. LEVEL OF PROOF: 4. PMID- 29789237 TI - Predictors of biochemical recurrence after radical prostatectomy in an Afro Caribbean population in Guadeloupe (French West Indies). AB - PURPOSE: Few studies have investigated predictive risk factors of biochemical recurrence (BCR) after radical prostatectomy (RP) in other than Caucasian and Asian populations. We aimed to identify pre- and post-operative predictors of BCR after RP in an Afro-Caribbean population in Guadeloupe (French West Indies). PATIENTS AND METHODS: The study included 964 patients who underwent RP for clinically localized prostate cancer between April 1, 2000 and December 31, 2010 in the University Hospital of Guadeloupe. The hazard ratio (HR) and corresponding 95% confidence interval (CI) for single variable associations with BCR were calculated using the Cox proportional hazards regression. Multiple variable analyses for association with BCR were performed, including all variables that reached statistical significance (P value<0.05) in univariate analysis. A backward selection model was then applied with a P value >=0.1 for retention in the final model. Sensitivity analysis was performed and restricted to patients with known values for all variables (complete case analysis). RESULTS: With a median follow-up of 4.8 years, the BCR rate was 26.7%. In multivariable analysis, predictors of BCR before surgery were diabetes mellitus type 2 (DT2) (HR: 1.37, 95% CI: 1.02-1.85; P=0.038), pre-operative PSA>7.5ng/ml (1.49, 1.15-1.92; P=0.002), clinical stage T2 (1.55, 1.21-1.98; P=0.0006), Gleason score>7 or 4+3 (2.12, 1.54-2.91; P<0.0001), and percentage of length of biopsy positive scores (1.66, 1.24-2.20; P=0.0006). Predictors of BCR after surgery were DT2 (HR: 1.37, 95% CI: 1.01-1.85; P=0.045), pre-operative PSA>7.5ng/ml (1.37, 1.06-1.79; P=0.018), pathological Gleason score>7 or 4+3 (2.36, 1.74-3.19; P<0.0001), pathological stage pT3b (1.68, 1.15-2.45; P=0.007), positive surgical margins (1.72, 1.32-2.45; P=0.0001), and perioperative blood loss>2000ml (3.74, 1.37 10.2; P=0.01). The results were virtually the same by sensitivity analysis (complete cases), except for DT2, which was associated with BCR with borderline statistical significance in the pre-operative model and not retained in the post operative model. CONCLUSIONS: Afro-Caribbean populations in French West Indies share the same major clinical and pathological risk factors of BCR after RP identified in other ethnic groups. Perioperative blood loss appears to be an additional and independent predictive factor of BCR. LEVEL OF PROOF: 4. PMID- 29789239 TI - Mandatory influenza vaccination and religious accommodation for healthcare workers: Lessons from recent legal challenges. PMID- 29789238 TI - A phase 1 study of safety and immunogenicity following intradermal administration of a tetravalent dengue vaccine candidate. AB - BACKGROUND: As part of the ongoing search for an effective dengue vaccine, Takeda performed a phase 1b study to investigate the safety and immunogenicity of an early low-dose tetravalent dengue vaccine candidate formulation (LD-TDV), based on an attenuated serotype 2 backbone, when administered intradermally with an injector device (PharmaJet(r)), or needle-syringe. METHODS: The study was performed in two centers in the US, in healthy 18-45 year old subjects with no history of dengue vaccination or disease. One or two vaccine doses were given on Day 0, and another dose or placebo on Day 90. Neutralizing antibodies were measured up to Day 270; safety was assessed as laboratory measurements and solicited and unsolicited adverse events on diary cards. RESULTS: Changes in World Health Organization prequalification guidance for new vaccines concerning storage conditions favored the use of lyophilized preparations, and led to the early cessation of enrolment, but not before 67 subjects were enrolled in four treatment groups. Sixty-five subjects completed the planned schedule. There were no safety signals or serious adverse events. All vaccination regimens elicited neutralizing antibodies. Titers of neutralizing antibodies against serotypes 1 and 2 were higher than those against serotypes 3 and 4. There were no consistent increases in responses with two doses given either concomitantly or 90 days apart. CONCLUSIONS: Simultaneous injection of two LD-TDV doses was shown to have the potential to improve seroconversion rates to serotypes 1 and 2, and to increase serotype 2 antibody titers. A primary dose of LD-TDV administered by PharmaJet was shown to induce more rapid seroconversion to serotypes 1, 2, and 3 compared with administration by needle-syringe (ClinicalTrials.gov: NCT01765426). PMID- 29789240 TI - Effect of maternal immunization against pertussis in Medellin and the metropolitan area, Colombia, 2016-2017. AB - BACKGROUND: In 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence. OBJECTIVE: To assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life. METHODS: A cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015-2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed. RESULTS: We observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16-21%]; umbilical cord: 23.1% [95% CI 19.2-27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000). CONCLUSION: The expected effect of Tdap maternal vaccination against pertussis was observed. PMID- 29789241 TI - Vaccines, inspiring innovation in health. AB - This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of vaccine supply in developing countries. PMID- 29789242 TI - 'What have you HEARD about the HERD?' Does education about local influenza vaccination coverage and herd immunity affect willingness to vaccinate? AB - BACKGROUND: Vaccination protects individuals directly and communities indirectly by reducing transmission. We aimed to determine whether information about herd immunity and local vaccination coverage could change an individual's vaccination plans and concern about influenza. METHODS: We surveyed Minnesota residents >=18 years during the 2016 Minnesota State Fair. Participants were asked to identify the definition of herd immunity, to report their history of and plans to receive influenza vaccine, to report their concern about influenza, and to estimate the reported influenza vaccination coverage in their county. After providing educational information about herd immunity and local vaccination rates, we reassessed vaccination plans and concerns. We used logistic regression to estimate predicted percentages for those willing to be vaccinated, for concern about influenza, and for changes in these outcomes after the intervention. We then compared those individuals with and without prior knowledge of herd immunity, accounting for other characteristics. RESULTS: Among 554 participants, the median age was 57 years; most were female (65.9%), white (91.0%), and non Hispanic/Latino (93.9%). Overall, 37.2% of participants did not know about herd immunity and 75.6% thought that the influenza vaccination coverage in their county was higher than it was reported. Those not knowledgeable about herd immunity were significantly less likely than those knowledgeable about the concept to report plans to be vaccinated at baseline (67.8% versus 78.9%; p = 0.004). After learning about herd immunity and influenza vaccination coverage, the proportion of those not knowledgeable about herd immunity who were willing to be vaccinated increased significantly by 7.3 percentage points (p = 0.001). Educating participants eliminated the significant difference in the proportion planning to be vaccinated between these two groups (80.1% of those knowledgeable and 75.1% of those who were not initially knowledgeable became willing; p = 0.148). CONCLUSIONS: Education about herd immunity and local vaccination coverage could be a useful tool for increasing willingness to vaccinate, generating benefits both to individuals and communities. PMID- 29789243 TI - MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial. AB - BACKGROUND: Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04 adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women. METHODS: In this phase IIIb study (NCT01755689), 1300 healthy 9-25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated. RESULTS: Immunogenicity of MenACWY-TT and AS04 HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04 HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, >=89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified. CONCLUSION: Our data support co-administration of MenACWY-TT with Tdap and AS04 HPV16/18 vaccines in adolescents. PMID- 29789244 TI - Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics. AB - BACKGROUND: Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist. AIM: The aim was to explore the patient perceptions of benefit from management of their sexual dysfunction by a biopsychosocial multi-disciplinary team. METHODS: A survey was e mailed to women patients seen by multi-disciplinary teams at 2 different settings: San Diego Sexual Medicine or Mayo Clinic Women's Health Clinic during a 27-month period. Data are reported using summary statistics for age and count for remaining survey responses. Cochran-Armitage tests for trend were used to compare pre- and post-comfort levels. OUTCOMES: Main outcome measures included perceived benefit of being managed in a team-based model of care, level of benefit and satisfaction from each provider, and difference from pre-conceived level of comfort to actual comfort after each provider visit. RESULTS: 89 of 270 e-mailed surveys were analyzed. Patient populations (mean age 47.6, range 23-77 years) were similar between sites. Overall, 82% of respondents reported moderate/great benefit from the team-based model; 72.1% reported management by all 3 providers valuable/extremely valuable; and 84.3% were somewhat/very satisfied with the model. Women endorsed specific ways in which they benefitted from the team-based model including: improved sexual function (58.1%), feeling validated (72.1%) and listened to (62.8%), that they better understood their health concerns (65.1%), that their partner better understood their health concerns (46.5%), and feeling normal (46.5%). There were no significant differences between the 2 clinics in terms of patient-perceived benefit, value, or satisfaction. CONCLUSIONS: The team based model of care for management of sexual dysfunction in women including a medical provider, physical therapist, and sex therapist is associated with patient-perceived benefit, satisfaction, and value. Rullo J, Faubion S, Hartzell R, et al. Biopsychosocial Management of Female Sexual Dysfunction: A Pilot Study of Patient Perceptions From 2 Multi-Disciplinary Clinics. Sex Med 2018;6:217-223. PMID- 29789245 TI - Outcomes of Arthroscopic Rotator Cuff Repair in Patients Who Are 70 Years of Age or Older Versus Under 70 Years of Age: A Sex- and Tear Size-Matched Case-Control Study. AB - PURPOSE: To compare the structural and clinical outcomes after arthroscopic rotator cuff repair (ARCR) of a case group aged 70 and above with those of a control group younger than 70, with the 2 groups matched for sex and tear size. METHODS: The case group, comprising 53 patients 70 or older, and the control group, comprising 159 patients younger than 70, all received ARCR to 1 shoulder with symptomatic full-thickness rotator cuff tear. The case and the control subjects, who were matched for sex and tear size to minimize bias related to tendon healing, received ARCR during the same period. The mean age was 71.8 +/- 2.6 years in the case group and 59.3 +/- 7.1 years in the control group. The minimum follow-up period was 1 year in both groups. Cuff integrity was evaluated using ultrasonography. Structural and clinical outcomes of the 2 groups were compared. RESULTS: Regarding structural outcomes, the complete healing, partial thickness retear, and full-thickness retear rates were 66% (35/53), 15% (8/53), and 19% (10/53) in the case group, and 68% (108/159), 19% (30/159), and 13% (21/159), respectively, in the control group. The 2 groups had no significantly different retear rates (P = .52). Regarding clinical outcomes, the mean improvements in range of motion, pain, muscle strength, and age- and sex-matched Constant scores were not significantly different between the 2 groups (P > .37). The preoperative tear size was significantly associated with retear in both studied groups (P = .02). CONCLUSIONS: The clinical and structural outcomes of ARCR in patients 70 or older with symptomatic full-thickness rotator cuff tear are comparable with those in patients younger than 70 with at least 1-year follow up. Preoperative tear size, a biological factor, is a strong predictor for retear. LEVEL OF EVIDENCE: Level III, a retrospective comparative (case-control) study. PMID- 29789246 TI - Arthroscopic Latarjet Techniques: Graft and Fixation Positioning Assessed With 2 Dimensional Computed Tomography Is Not Equivalent With Standard Open Technique. AB - PURPOSE: To analyze graft and fixation (screw and EndoButton) positioning after the arthroscopic Latarjet technique with 2-dimensional computed tomography (CT) and to compare it with the open technique. METHODS: We performed a retrospective multicenter study (March 2013 to June 2014). The inclusion criteria included patients with recurrent anterior instability treated with the Latarjet procedure. The exclusion criterion was the absence of a postoperative CT scan. The positions of the hardware, the positions of the grafts in the axial and sagittal planes, and the dispersion of values (variability) were compared. RESULTS: The study included 208 patients (79 treated with open technique, 87 treated with arthroscopic Latarjet technique with screw fixation [arthro-screw], and 42 treated with arthroscopic Latarjet technique with EndoButton fixation [arthro EndoButton]). The angulation of the screws was different in the open group versus the arthro-screw group (superior, 10.3 degrees +/- 0.7 degrees vs 16.9 degrees +/- 1.0 degrees [P < .001]; inferior, 10.3 degrees +/- 0.8 degrees vs 15.7 degrees +/- 0.9 degrees [P < .0001]). The angulation of the EndoButtons was 5.7 degrees +/- 0.5 degrees ; this was different from that of open inferior screws (P = .003). In the axial plane (level of equator), the arthroscopic techniques resulted in lateral positions (arthro-screw, 1.5 +/- 0.3 mm lateral [P < .001]; arthro-EndoButton, 0 +/- 0.3 mm lateral [P < .0001]) versus the open technique (0.9 +/- 0.2 mm medial). At the level of 25% of the glenoid height, the arthroscopic techniques resulted in lateral positions (arthro-screw, 0.3 +/- 0.3 mm lateral [P < .001]); (arthro-EndoButton, 0.7 +/- 0.3 mm lateral [P < .0001]) versus the open technique (1.0 +/- 0.2 mm medial). Higher variability was observed in the arthro-screw group. In the sagittal plane, the arthro-screw technique resulted in higher positions (55% +/- 3% of graft below equator) and the arthro-EndoButton technique resulted in lower positions (82% +/- 3%, P < .0001) versus the open technique (71% +/- 2%). Variability was not different. CONCLUSIONS: This study shows that the position of the fixation devices and position of the bone graft with the arthroscopic techniques are statistically significantly different from those with the open technique with 2-dimensional CT assessment. In the sagittal plane, the arthro-screw technique provides the highest positions, and the arthro-EndoButton technique, the lowest. Overall, the mean position of the bone block with the open Latarjet technique in the axial plane is slightly medial to the joint line, as recommended. Conversely, with the arthroscopic techniques, the bone grafts are more lateral with a slight overhang. The main differences are observed in the dispersion of the values (more extreme positions) with the arthro-screw technique, given the acknowledged limitations. Despite the statistical significance, the clinical significance of these differences is yet unknown. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 29789247 TI - Preoperative Depression Is Negatively Associated With Function and Predicts Poorer Outcomes After Hip Arthroscopy for Femoroacetabular Impingement. AB - PURPOSE: (1) To determine the prevalence of depression in patients undergoing hip arthroscopy for the treatment of femoroacetabular impingement (FAI) syndrome and (2) to determine whether depression has a statistically significant and clinically relevant effect on preoperative and postoperative patient-reported outcome scores. METHODS: Consecutive subjects undergoing hip arthroscopy for FAI syndrome were retrospectively reviewed. The Beck Depression Inventory-II (BDI II), Hip Outcome Score (HOS), and 33-item International Hip Outcome Tool (iHOT 33) were administered preoperatively and postoperatively. Clinically relevant differences were defined by the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state. Comparisons between preoperative and postoperative scores were completed. The Spearman correlation coefficient (r) was used to determine the degree of correlation between the BDI-II score, HOS, and iHOT-33 score preoperatively and postoperatively. RESULTS: We analyzed 77 patients (72.7% female patients; mean age, 35.2 +/- 12.5 years). Depressive symptoms were reported as minimal (75.3%), mild (11.7%), moderate (6.5%), or severe (6.5%). Patients with minimal or mild depression had a superior HOS Activities of Daily Living (Delta17.3 preoperatively [P < .001] and Delta37.8 postoperatively [P < .001]), HOS Sport Specific Subscore (Delta12.8 preoperatively [P = .002] and Delta52.1 postoperatively [P < .0001]), and iHOT-33 score (Delta15.4 preoperatively [P < .0001] and Delta51.3 postoperatively [P < .0001]) compared with patients with moderate or severe depression. There was a weak to moderate negative correlation between the BDI-II score and iHOT-33 score (r = -0.4614, P < .0001 preoperatively; r = -0.327, P < .0001 at 1 year), HOS Activities of Daily Living (r = -0.531, P < .0001 preoperatively), and HOS Sport-Specific Subscore (r = 0.379, P < .0017 at 1 year). CONCLUSIONS: Most patients undergoing hip arthroscopy for FAI have minimal depressive symptoms with the overall prevalence higher than the general population. Patients with minimal or mild depressive symptoms have statistically and clinically better preoperative and postoperative patient-reported outcomes, are more likely to obtain substantial clinical benefit from surgery, and are more likely to reach a patient acceptable symptom state after surgery than patients with moderate to severe depressive symptoms. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 29789248 TI - Native Enthesis Preservation Versus Removal in Rotator Cuff Repair in a Rabbit Model. AB - PURPOSE: The purpose of this study was to explore whether preservation of native enthesis during rotator cuff repair (RCR) results in a histologically and biomechanically better rotator cuff-greater tuberosity (RC-GT) connection in an animal model. METHODS: Thirty-six New Zealand white rabbits were used in this study. The supraspinatus tendons were cut from the footprint to create a rotator cuff tear (RCT) on both shoulders, followed by immediate repair, with a 1 mm thick tendon stump remaining on the footprint. On one side, RCR was performed by attaching the medial rotator cuff to the GT over the footprint stump layer (enthesis preservation [EP] approach). On the other side, the footprint stump and enthesis were fully removed and the footprint was decorticated. The repair was performed by attaching the medial rotator cuff onto the spongy bone surface in the footprint area (enthesis removal [ER] approach). Twelve rabbits were sacrificed at 4, 8, and 12 weeks, of which 6 were used for histological analysis and 6 for biomechanical evaluation. RESULTS: Histological examination revealed that in the EP group, the native enthesis healed well with the reattached cuff tendon, and continuous collagen crossed the tendon-tendon interface area at 12 weeks. However, in the ER group, there was only fibrous scar tissue formation at the tendon-bone interface. Biomechanical testing revealed a significantly higher load to failure (P = .001) of the RC-GT structure in the EP group than that in the ER group at 12 weeks. CONCLUSIONS: For acute RCT with remnant enthesis, EP RCR incorporates the native enthesis functionally in the restored RC-GT connection and enhances the RC-GT connection when compared with ER-RCR at 12 weeks in a rabbit model. CLINICAL RELEVANCE: This finding justifies a human trial because in RCR with a remnant footprint, the EP technique may be adopted for a better RC-GT connection. PMID- 29789249 TI - The Relationship of Femoral Tunnel Positioning in Medial Patellofemoral Ligament Reconstruction on Clinical Outcome and Postoperative Complications. AB - PURPOSE: To analyze the relation of the femoral tunnel (FT) positioning on clinical outcome. METHODS: Patients with recurrent patellar dislocation who underwent medial patellofemoral ligament (MPFL) reconstruction with or without tibial tubercle osteotomy between 1998 and 2012 were included in this retrospective study. Strict postoperative lateral radiographs were mandatory. Knees with previous osseous stabilization surgery, fixed lateral patellar dislocation, valgus knee (>5 degrees ), or open growth plates were excluded. The distance between the FT and the validated radiographic landmark (the "Schoettle point") was measured. An FT with a distance greater than 10 mm was considered as malpositioned. The distance was correlated to subjective outcome measurements (patient satisfaction and Kujala score) and postoperative complications (a loss of range of motion and revision surgery). RESULTS: Sixty-three knees in 60 patients (aged 23.7 +/- 7.5 years at the time of surgery, 79.4% female) were included with a mean follow-up of 5.7 +/- 3.3 years. The FT showed an average distance of 13.3 mm (+/-6.0 mm; 95% confidence interval [CI]: 11.7-14.8) to the Schoettle point, and 45 of 63 knees (71.4%) were deemed malpositioned. The postoperative Kujala score of malpositioned FT (75.9 points; 95% CI: 71.2-80.7) was not significantly inferior to knees with an FT within 10 mm (80.5; 95% CI: 73.7-87.3, P = .315). However, all 5 knees that underwent revision surgery showed an FT outside the 10-mm area. CONCLUSIONS: Malpositioning of the FT in MPFL reconstruction is associated with postoperative complications. However, a malpositioned FT in MPFL reconstruction will not necessarily lead to an unsatisfactory subjective or objective clinical outcome. Other factors, such as surgical indication or graft tensioning, might also significantly influence postoperative outcome. LEVEL OF EVIDENCE: Level IV, case-control study. PMID- 29789250 TI - Sectioning of the Anterior Intermeniscal Ligament Changes Knee Loading Mechanics. AB - PURPOSE: The purpose of this cadaver research project was to describe the biomechanical consequences of anterior intermeniscal ligament (AIML) resection on menisci function under load conditions in full extension and 60 degrees of flexion. METHODS: Ten unpaired fresh frozen cadaveric knees were dissected leaving the knee joint intact with its capsular and ligamentous attachments. The femur and tibia were sectioned 15 cm from the joint line and mounted onto the loading platform. A linear motion x-y table allows the tibial part of the joint to freely translate in the anterior-posterior direction. K-scan sensors were used to define contact area, contact pressure, and position of pressure center of application (PCOA). Two series of analysis were planned: before and after AIML resection, mechanical testing was performed with specimens in full extension (1,400 N load) and in 60 degrees of flexion (700 N load) to approximate heel strike and foot impulsion during the gait. RESULTS: Sectioning of the AIML produced mechanical variations below the 2 menisci when specimens were at full extension and loaded to 1,400 N: increasing the mean contact pressure (delta 0.4 +/- 0.2 MPa, +15% variation P = .008) and maximum contact pressure (delta 1.50 +/ 0.8 MPa, 15% variation P < .0001) and decreasing of tibiofemoral contact area (delta 71 +/- 51 mm2, -15% variation P < .0001) and PCOA (delta 2.1 +/- 0.8 mm). At 60 degrees flexion, significant differences regarding lateral meniscus mechanical parameters were observed before and after AIML resection: mean contact pressure increasing (delta 0.06 +/- 0.1 MPa, +21% variation P = .001), maximal contact-pressure increasing (delta 0.17 +/- 0.9 MPa, +28% variation P = .001), mean contact area decreasing (delta 1.84 +/- 8 mm2, 4% variation P = .3), and PCOA displacement to the joint center (mean displacement 0.6 +/- 0.5 mm). CONCLUSIONS: The section of the intermeniscal ligament leads to substantial changes in knee biomechanics, increasing femorotibial contact pressures, decreasing contact areas, and finally moving force center of application, which becomes more central inside the joint. CLINICAL RELEVANCE: AIML resection performed ex vivo in this study, might potentially be deleterious in vivo. Clinical studies focusing on preserving or even repairing the AIML are needed to evaluate those ex vivo elements. PMID- 29789251 TI - Influence of Tonnis Grade on Outcomes of Arthroscopic Management of Symptomatic Femoroacetabular Impingement. AB - PURPOSE: To define the outcomes of arthroscopic correction of femoroacetabular impingement (FAI) based on Tonnis findings within a previously reported patient population, including a comparative analysis of Tonnis grade 0 and 1 versus grade 2 changes. METHODS: Outcomes (modified Harris Hip Score [mHHS]) of a previously published study of arthroscopic correction of FAI were correlated with Tonnis grade. The inclusion criteria were the first 100 consecutive patients undergoing arthroscopic FAI correction with minimum 2-year follow-up. These procedures were performed between December 2003 and May 2006. Grades were determined independently by 2 experienced clinicians. Tonnis grades 0 and 1 were compared with Tonnis grade 2. Independent variables of sex and age were also evaluated. RESULTS: The average age of the entire group was 34.7 years (range, 13-76 years), with 66 male and 34 female patients. Of the patients, 17 had Tonnis grade 0, 49 had Tonnis grade 1, 29 had Tonnis grade 2, and 4 had Tonnis grade 3 (1 unknown). The average mHHS improvement for Tonnis grade 0 was 20.6 points; Tonnis grade 1, 22.2 points; Tonnis grade 2, 14.9 points; and Tonnis grade 3, 18.8 points. The improvement was statistically (P < .01) and clinically (>8 points) significant across all Tonnis grades. There was no difference (P = .077) between Tonnis grades 0 and 1 (21.8 points) versus grade 2 (14.9 points). There was no difference based on sex or age. CONCLUSIONS: These data support that statistically and clinically meaningful successful patient-reported outcomes (mHHS) at 2 years can be encountered even in the presence of Tonnis grade 2 radiographic features. Neither age nor sex was an indicator of poorer results within similar Tonnis grades. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 29789252 TI - A History of Anterior Cruciate Ligament Reconstruction at the National Football League Combine Results in Inferior Early National Football League Career Participation. AB - PURPOSE: To evaluate whether players with a history of an anterior cruciate ligament reconstruction (ACLR) before the National Football League (NFL) Combine played or started fewer games and/or participated in fewer eligible snaps compared with NFL Combine participants without a history of knee injury or surgery. METHODS: We performed a retrospective review of all players who participated in the NFL Combine between 2009 and 2015 and who had a history of an ACLR. NFL Combine participants were included if they had a previous ACLR or combined anterior cruciate ligament (ACL) injury and nonoperatively managed medial collateral ligament injury. The number of games started, number of games played, draft number, overall draft pick, and snap percentage for each position were determined. The mean value of each outcome metric was compared between case and control players. RESULTS: We identified 110 players who had an ACL injury (n = 76) or a combined ACL and medial collateral ligament injury (n = 34). Players in the ACLR group had a significantly worse mean draft pick number (difference of 30.2, P = .002) and mean draft round (difference of 0.8, P = .019) versus controls. Compared with control players, players in the ACLR group started and played significantly fewer games in both season 1 (difference of 2.7 games started, P < .001; difference of 2.7 games played, P < .001) and season 2 (difference of 7.4 games started, P < .001; difference of 3.0 games played, P = .003) and had a significantly lower snap percentage in both season 1 (difference of 23.1%, P < .001) and season 2 (difference of 24.0%, P < .001). CONCLUSIONS: Athletes at the NFL Combine who previously underwent an ACLR had significantly lower early-career NFL player metrics, including fewer games started, fewer games played, and a lower snap percentage, than uninjured controls. Defensive linemen, defensive backs, and linebackers were the 3 most affected positions. Players with a prior ACLR and combined meniscal-chondral pathology had significantly lower numbers of games started and games played in seasons 1 and 2 and a significantly lower season 2 snap percentage. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 29789253 TI - Topographic Analysis of 2 Alternative Donor Sites of the Ipsilateral Elbow in the Treatment of Capitellar Osteochondritis Dissecans. AB - PURPOSE: To find the best topographic subchondral bone match between the capitellum and 2 proposed alternative donor sites of the ipsilateral elbow for capitellar osteochondral autologous transplantation: the non-articulating part of the radial head and the lateral olecranon tip. METHODS: In our retrospective database, 20 patients with an unremarkable computed tomography scan of the elbow despite clinical suspicion were identified for analysis. Included were patients aged 11 to 20 years with intact osseous structures and a computed tomography slice thickness of 1.25 mm or less. Three-dimensional polygon models were created using a standard predefined threshold, after which 4 articular surface lesions on the capitellum were created: central 40 degrees , central 60 degrees , lateral 40 degrees , and lateral 60 degrees . In addition, 3 donor locations on the non articulating part of the radial head (diameter, 5 mm) and the lateral olecranon tip (diameter, 3.5 mm) were created. For each of 24 donor-recipient combinations, the donor graft surface was virtually placed on the recipient surface to quantify the mean distance between surfaces. RESULTS: The group of 20 patients consisted of 16 male and 4 female patients with a mean age of 15.9 years (range, 12-18 years). For a central 40 degrees lesion, the mean distance across all 6 donor recipient combinations ranged from 0.085 +/- 0.023 to 0.118 +/- 0.036 mm; for a central 60 degrees lesion, the mean distance ranged from 0.075 +/- 0.018 to 0.117 +/- 0.062 mm; for a lateral 40 degrees lesion, the mean distance ranged from 0.087 +/- 0.030 to 0.182 +/- 0.226 mm; and for a lateral 60 degrees lesion, the mean distance ranged from 0.084 +/- 0.048 to 0.115 +/- 0.045 mm. There were no differences in topographic matching between donor-recipient combinations. CONCLUSIONS: The findings of this study show a less than 0.2-mm difference in the topographic subchondral bone match between 4 common lesion locations on the capitellum and 2 alternative donor sites of the ipsilateral elbow for capitellar osteochondral autologous transplantation: the non-articulating part of the radial head and the lateral olecranon tip. CLINICAL RELEVANCE: These findings suggest that the non-articulating part of the radial head and the lateral olecranon tip may potentially be used as a donor source when treating capitellar osteochondritis dissecans. PMID- 29789254 TI - Prediction of the Irreparability of Rotator Cuff Tears. AB - PURPOSE: To determine the influence of preoperative factors on reparability of rotator cuff tears (RCTs) and yield a predictive model for predicting irreparability preoperatively. METHODS: Among patients with full-thickness RCTs, the reparable group underwent arthroscopic rotator cuff repairs for reparable RCTs whereas the irreparable group underwent alternative surgical procedures for irreparable RCTs. We analyzed age, sex, chronic pseudoparalysis (CPP), mediolateral and anteroposterior tear sizes, acromiohumeral distance (AHD), tangent sign, fatty infiltration (FI) (group 1, Goutallier stage 0 or 1; and group 2, Goutallier stage 2, 3, or 4), and tendon involvement (TI) (type 1, supraspinatus; type 2, supraspinatus and subscapularis; type 3, supraspinatus and infraspinatus; and type 4, all 3 tendons). RESULTS: The irreparability rate was 12.5%. Between the reparable (663 patients) and irreparable (95 patients) groups, significant differences were found in age (58.8 +/- 8.3 years vs 65.6 +/- 8.0 years, P < .001); female sex (46.9% vs 63.2%, P = .014); CPP (6.5% vs 36.8%, P < .001); mediolateral tear size (23.7 +/- 12.1 mm vs 47.4 +/- 9.1 mm, P < .001); anteroposterior tear size (17.9 +/- 11.5 mm vs 43.4 +/- 16.2 mm, P < .001); AHD (9.0 +/- 1.7 mm vs 5.8 +/- 1.6 mm, P < .001); tangent sign (2.9% vs 61.1%, P < .001); group 2 FI of the subscapularis (6.9% vs 20.0%, P < .001), supraspinatus (12.1% vs 58.9%, P < .001), infraspinatus (26.8% vs 69.5%, P < .001), and teres minor (4.2% vs 10.5%, P = .008); and type 1, 2, 3, and 4 TI (88.1%, 6.2%, 5.4%, and 0.3%, respectively, vs 29.5%, 21.1%, 28.4%, and 21.1%, respectively; P < .001). Multiple logistic regression analysis showed CPP, mediolateral tear size, AHD, tangent sign, group 2 FI of the supraspinatus, and type 4 TI were significant independent predictors of irreparability, with odds ratios of 3.539 (P = .007), 1.087 (P < .001), 0.624 (P < .001), 6.141 (P < .001), 2.233 (P = .034), and 12.350 (P = .016), respectively. These factors yielded a predictive model for irreparability as follows: Logit P = 1.264 * CPP + 0.084 * Mediolateral tear size - 0.472 * AHD + 0.804 * Group 2 FI of supraspinatus + 1.815 * Tangent sign + 2.514 * Type 4 TI - 3.460. CONCLUSIONS: The irreparability of RCTs is strongly associated with CPP, mediolateral tear size, AHD, tangent sign, group 2 FI of the supraspinatus, and type 4 TI and can be preoperatively calculated using the predictive equation. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 29789255 TI - Combined Tibial Tubercle Osteotomy and Medial Patellofemoral Ligament Reconstruction for Recurrent Lateral Patellar Instability in Patients With Multiple Anatomic Risk Factors. AB - PURPOSE: To report the outcomes for combined tibial tubercle osteotomy (TTO) and medial patellofemoral ligament (MPFL) reconstruction and assess for potential risk factors for recurrent instability and/or poor outcomes. METHODS: The medical record at our institution was reviewed for patients treated with MPFL reconstruction and TTO for recurrent lateral patellar instability from 1998 to 2014. Preoperative imaging was assessed for trochlear dysplasia according to the Dejour classification (high grade = B, C, D) and the presence of patella alta using the Caton-Deschamps ratio (>1.2). The indication for combined MPFL reconstruction and TTO was MPFL insufficiency and a lateralized tibial tubercle. Outcomes were determined by recurrent instability, return to sport, and Kujala and International Knee Documentation Committee (IKDC) scores. RESULTS: Thirty knees in 28 patients (14 M, 14 F) with a mean age of 22.6 +/- 9.1 years (range, 13-51 years) were included with a mean follow-up of 48 +/- 28 months (24-123 months). Seventy-three percent (22/30) had high-grade trochlear dysplasia, and 63% (19/30) had patella alta. One patient had a postoperative dislocation and 1 had a subluxation event. The Caton-Deschamps ratio decreased by a mean of 0.2 (P = .001), leaving 30% with postoperative patella alta. The mean postoperative scores were as follows: Tegner = 5 +/- 2, Kujala = 89 +/- 16 (45-100), and IKDC = 85 +/- 17 (44-100). Eighty-three percent (15/18) returned to their preoperative sport. Female gender was a risk factor for lower IKDC (77.3 vs. 92.6, P = .01) and Kujala (82.2 vs. 95.0, P = .03) scores. Medialization greater than 10 mm was directly correlated to lower IKDC (P = .02) and Kujala (P = .01) scores. CONCLUSIONS: The combination of MPFL reconstruction and TTO in patients with trochlear dysplasia results in low recurrence of instability. Patients on average had good subjective outcomes and were able to return to sport. Female gender and tibial tubercle medialization greater than 10 mm were associated with worse outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 29789256 TI - Systems-level analysis of risk genes reveals the modular nature of schizophrenia. AB - Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent genome-wide association studies) have identified many risk genes for schizophrenia. However, the physical interactions among the proteins encoded by schizophrenia risk genes remain elusive and it is not known whether the identified risk genes converge on common molecular networks or pathways. Here we systematically investigated the network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions (PPI) from the human interactome. We found that schizophrenia risk genes encode a densely interconnected PPI network (P = 4.15 * 10-31). Compared with the background genes, the schizophrenia risk genes in the interactome have significantly higher degree (P = 5.39 * 10-11), closeness centrality (P = 7.56 * 10-11), betweeness centrality (P = 1.29 * 10-11), clustering coefficient (P = 2.22 * 10-2), and shorter average shortest path length (P = 7.56 * 10-11). Based on the densely interconnected PPI network, we identified 48 hub genes and 4 modules formed by highly interconnected schizophrenia genes. We showed that the proteins encoded by schizophrenia hub genes have significantly more direct physical interactions. Gene ontology (GO) analysis revealed that cell adhesion, cell cycle, immune system response, and GABR-receptor complex categories were enriched in the modules formed by highly interconnected schizophrenia risk genes. Our study reveals that schizophrenia risk genes encode a densely interconnected molecular network and demonstrates the modular nature of schizophrenia. PMID- 29789257 TI - HIV pre-exposure prophylaxis: Exploring the potential for expanding the role of pharmacists in public health. AB - OBJECTIVES: The study objectives were to a) assess knowledge and experience; b) describe perceptions and attitudes; and c) identify training needs of community based pharmacists regarding HIV pre-exposure prophylaxis (PrEP). DESIGN: This was a cross-sectional survey study. SETTING AND PARTICIPANTS: The survey was administered online to pharmacists practicing in a community setting in the state of Minnesota. OUTCOME MEASURES: Measures included knowledge of and experience with HIV PrEP, perceptions and attitudes towards pharmacists' involvement, and HIV PrEP-specific training needs for pharmacists. RESULTS: With a survey response rate of approximately 13% (n = 347), most respondents (76.4%) agreed that HIV PrEP can be beneficial in high-risk populations. Forty-six percent of respondents were not aware of U.S. Food and Drug Administration approval of emtricitabine and tenofovir disoproxil fumarate for PrEP. Most respondents (71.1%) were "not at all familiar" with Centers for Disease Control and Prevention guidelines for PrEP. Twenty-one percent of respondents had sufficient knowledge to counsel patients on PrEP. Experience with counseling on PrEP (21.8%), having dispensed PrEP in the last 2 years (33.1%), fewer years in practice (<=10 years), location of practice site (urban or suburban), and having received HIV continuing education in the last 2 years (33.0%) were associated with more knowledge of HIV PrEP. Top concerns with counseling were knowledge about the medication and behavior modification. The most frequently indicated primary concerns with implementing PrEP initiatives were identifying appropriate candidates and patient adherence. CONCLUSION: As pharmacists' roles continue to expand, relevant content in pharmacy education and requisite training (including continuing education) are critical to addressing knowledge gaps and competencies that will enable pharmacists engage more effectively in public health efforts such as HIV prevention. PMID- 29789258 TI - Design, synthesis and biological evaluation of artemisinin derivatives containing fluorine atoms as anticancer agents. AB - Ten novel artemisinin derivatives containing fluorine atoms were synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS technologies in this study. The in vitro cytotoxicity against U87MG, SH-SY5Y, MCF-7, MDA-MB-231, A549 and A375 cancer cell lines was evaluated by MTT assay. Compound 9j was the most potent anti-proliferative agent against the human breast cancer MCF-7 cells (IC50 = 2.1 MUM). The mechanism of action of compound 9j was further investigated by analysis of cell apoptosis and cell cycle. Compound 9j induced cell apoptosis and arrested cell cycle at G1 phase in MCF-7 cells. Our promising findings indicated that the compound 9j could stand as potential lead compound for further investigation. PMID- 29789259 TI - Synthesis, characterization and cytotoxicity studies of 1,2,3-triazoles and 1,2,4 triazolo [1,5-a] pyrimidines in human breast cancer cells. AB - Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is essential for physiological functions of tissues and neovasculature. VEGFR signaling is associated with the progression of pathological angiogenesis in various types of malignancies, making it an attractive therapeutic target in cancer treatment. In the present work, we report the synthesis of 1,4-disubstituted 1,2,3-triazoles and 1,2,4-triazolo[1, 5-a]pyrimidine derivatives via copper (I)-catalyzed azide alkyne cycloaddition (CuAAC) reaction and screened for their anticancer activity against MCF7 cells. We identified 1-(2'-ethoxy-4'-fluoro-[1,1'-biphenyl]-4-yl)-4 phenyl-1H-1,2,3-triazole (EFT) as lead cytotoxic agent against MCF7 cell lines with an IC50 value of 1.69 uM. Further evaluation revealed that EFT induces cytotoxicity on Ishikawa, MDA-MB-231 and BT474 cells with IC50 values of 1.97, 4.81 and 4.08 uM respectively. However, EFT did not induce cytotoxicity in normal lung epithelial (BEAS-2B) cells. Previous reports suggested that 1,2,3-triazoles are the inhibitors of VEGFR1 and therefore, we evaluated the effect of EFT on the expression of VEGFR1. The results demonstrated that EFT downregulates the expression of VEGFR1 in MCF7 cells. In summary, we identified a potent cytotoxic agent that imparts its antiproliferative activity by targeting VEGFR1 in breast cancer cells. The novel compound could serve as a lead structure in developing VEGFR1 inhibitors. PMID- 29789260 TI - Respondent driven sampling in a biomonitoring study of refugees from Burma in Buffalo, New York who eat Great Lakes fish. AB - BACKGROUND: Refugees from Burma who consume fish caught from local waterbodies have increased risk of exposure to environmental contaminants. We used respondent driven sampling (RDS) to sample this hard-to-reach population for the first Biomonitoring of Great Lakes Populations program. In the current study, we examined the interview data and assessed the effectiveness of RDS to sample the unique population. METHODS: In 2013, we used RDS to sample 205 Burmese refugees and immigrants residing in Buffalo, New York who consumed fish caught from Great Lakes waters. RDS-adjusted population estimates of sociodemographic characteristics, residential history, fish consumption related behaviors, and awareness of fish advisories were obtained. We also examined sample homophily and equilibrium to assess how well the RDS assumptions were met in the study. RESULTS: Our sample was diverse with respect to sex, age, years residing in Buffalo, years lived in a refugee camp, education, employment, and fish consumption behaviors, and each of these variables reached equilibrium by the end of recruitment. Burmese refugees in Buffalo consumed Great Lakes fish throughout the year; a majority of them consumed the fish more than two times per week during summer, and about one third ate local fish more than once per week in winter. An estimated 60% of Burmese refugees in Buffalo had heard about local fish advisories. CONCLUSIONS: RDS has the potential to be an effective methodology for sampling refugees and immigrants in conducting biomonitoring and environmental exposure assessment. Due to high fish consumption and limited awareness and knowledge of fish advisories, some refugee and immigrant populations are more susceptible to environmental contaminants. Increased awareness on local fish advisories is needed among these populations. PMID- 29789261 TI - Corrigendum to "Oleamide suppresses inflammatory responses in LPS-induced RAW264.7 murine macrophages and alleviates paw edema in a carrageenan-induced inflammatory rat model" [Int. Immunopharmacol. 56 (2018) 179-185]. PMID- 29789262 TI - Eccentric cycling emphasising a low cardiopulmonary demand increases leg strength equivalent to workload matched concentric cycling in middle age sedentary males. AB - OBJECTIVES: This study determined if eccentric endurance cycling, eliciting a low cardiovascular demand, could stimulate muscle strength adaptations in sedentary middle-aged males. DESIGN: Twenty-four middle-aged sedentary males were allocated to concentric (CON) or matched workload eccentric (ECC) cycling (60% peak concentric workload) according to their maximal voluntary isometric quadriceps strength. METHODS: Seventeen participants [42.7+/-8.3 years, BMI 28.6+/-5.2, peak oxygen consumption [30.5+/-5.8mLkg-1min-1] completed 8 weeks (2 sessions per week) of CON (n=8) or ECC (n=9) cycle training. Incline leg press (6RM), maximal voluntary isometric contraction (MVIC) torque of the quadriceps and peak oxygen consumption were measured at baseline and 8 weeks. RESULTS: Eccentric cycle training resulted in low cardiovascular demand (CON 154+/-2; ECC 95+/-3bmin 1P<0.05) and ratings of perceived exertion (CON 14.9+/-0.3; ECC 9.5+/-0.3/20 P<0.05). Peak oxygen consumption improved within the CON group (Baseline 27.4+/ 2.1; 8 weeks: 30.0+/-1.7mLkg-1min-1P<0.05) and not within the ECC group (Baseline 33.2+/-1.5; 8 weeks 33.3+/-1.6mLkg-1min-1) following training. 6RM (CON 176+/-20; ECC 192+/-11kg) and MVIC (CON 199+/-25; ECC 199+/-25Nm) strength were equivalent at baseline (P>0.05). Both groups significantly increased 6RM (CON 13.0+/-3.0; ECC 10.7+/-3.2%) and MVIC (CON 12.9+/-4.3; ECC 18.8+/-3.0%) relative to their own baseline (P<0.05). Therefore, improved leg strength was equivalent between CON and ECC groups despite the varied training (P>0.05). CONCLUSIONS: In sedentary middle age males, eccentric endurance cycling with a low cardiovascular demand, increased both quadriceps isometric and 6RM strength comparable to a matched workload concentric cycling program. PMID- 29789263 TI - Gross motor skills in toddlers: Prevalence and socio-demographic differences. AB - OBJECTIVES: Gross motor skills (GMS) are a vital component of a child's development. Monitoring levels and correlates of GMS is important to ensure appropriate strategies are put in place to promote these skills in young children. The aim of this study was to describe the current level of GMS development of children aged 11-29months and how these levels differ by age, sex, BMI and socio-economic status. DESIGN: Cross-sectional study. METHODS: This study involved children from 30 childcare services in NSW, Australia. GMS were assessed using the Peabody Developmental Motor Scales Second Edition. Prevalence was reported using the gross motor quotient and both raw and standard scores for locomotor, object manipulation and stationary subtests. Socio-demographics were collected via parent questionnaires. Analyses included t-tests, chi-square tests, one-way ANOVA and linear regression models. RESULTS: This study included 335 children (mean age=19.80+/-4.08months, 53.9% boys). For the gross motor quotient, 23.3% of the children scored below average. For the GMS subtests, 34.3% of children scored below average for locomotion, 10.1% for object manipulation and 0.3% for stationary. Boys were more proficient in object manipulation than girls (p=0.001). GMS were negatively associated with age and a higher socio-economic status (all p<0.05). There were no associations for BMI. CONCLUSIONS: This is the first descriptive study to show the prevalence of below average at locomotor skills in toddlers is higher than reported in normative samples. Early commencement of GMS promotion is recommended with a focus on locomotor skills and girls' object manipulation skills. PMID- 29789264 TI - Talent identification for soccer: Physiological aspects. AB - OBJECTIVES: Soccer coaches are always looking to discover the next star player, without investing the necessary resources, time, and effort into a player's development. In the modern era, talent identification in soccer seems to be a comparative process rather than a developmental process. This article will look at the physiological profiles of soccer players in the modern era and how testing and talent identification processes should coincide with this data. DESIGN: An extensive literature search identifying the physiological attributes of soccer players that are required to compete at an elite level was conducted. An examination of the methods to test these attributes was also conducted. METHODS: Studies were assigned into three areas to understand the physiological aspect of soccer: physiological testing methods, benchmark values, and correlations between different tests. RESULTS: A testing battery was established to test the key physiological attributes of prospective youth soccer players. Benchmark levels were also identified to allow coaches to understand areas of improvement. CONCLUSIONS: Using a physiological testing battery will allow teams to track their players' progress throughout their developmental years. This allows coaches to consistently identify a player's strengths and weaknesses, as well as allow players who may experience late maturation to still be identified. PMID- 29789265 TI - The physiological and perceptual demands of running on a curved non-motorised treadmill: Implications for self-paced training. AB - OBJECTIVES: To compare physiological and perceptual response of running on a curved non-motorized treadmill (cNMT) with running on a motorized treadmill (MT), and to determine the running velocity at which a physiological response>=90% VO2max was elicited. DESIGN & METHODS: 13 trained male runners (mean+/-SD; 36+/ 11years, 1.80+/-0.06m, 70+/-4kg, VO2max: 57.3+/-3.5 mLkg-1min-1) performed an incremental running test on a MT to determine VO2max and the accompanying maximum velocity (Vmax). Participants first completed a familiarization session on the cNMT. Next, participants ran for 4min at five/six progressively higher velocities (40-90% Vmax). These runs were completed on the cNMT and MT in two separate visits in a randomized and counterbalanced order. RESULTS: No participant was able to complete the 4min run at 80% Vmax on the cNMT. Running on the cNMT elicit a higher relative oxygen uptake (%VO2max) across all velocities compared to the MT (32.5+/-5%, p<0.001, ES 3.3+/-0.9), and was accompanied by significantly higher heart rates (16.8+/-3%, p<0.001, ES 3.4+/-1.5), an altered cadence (2.6+/ 0.7%, p<0.001, ES 0.8+/-0.3) and ratings of perceived exertion (27.2+/-5%, p<0.001, ES 2.3+/-0.6). A less efficient running economy was evident when running on the cNMT (+38.4+/-16%, p<0.001, ES 2.73). Individual (n=9) linear interpolation predicted an exercise intensity of 90% VO2max was achieved in the non-motorized condition when running at 62.1+/-3.5% Vmax (R2=0.986+/-0.01), which was lower than MT run in which 90% VO2max was achieved at 81.4+/-5.6% Vmax (R2=0.985+/-0.02; 29.8+/-8%, p<0.001, ES 3.87). CONCLUSIONS: Running on the cNMT has higher physiological and perceptual demands and increases cadence. PMID- 29789266 TI - Microvascular volume in symptomatic Achilles tendons is associated with VISA-A score. AB - OBJECTIVES: The role of neovascularisation in tendinopathy is still poorly understood, potentially due to technical limitations of conventional power Doppler ultrasound. This study aimed to investigate the association between contrast-enhanced ultrasound (CEUS) microvascular volume (MV), Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and intrinsic Achilles tendon tenderness, as well as two different Power Doppler modes. DESIGN: Cross sectional study. METHODS: 20 individuals with uni- or bilateral Achilles tendinopathy completed a VISA-A questionnaire, and underwent microvascular volume measurements of the Achilles tendon mid-portion using both conventional, ultrasensitive (SMITM) power Doppler ultrasound and CEUS. Intrinsic tendon tenderness was assessed with sensation detection threshold to extracorporeal shock waves (ESW). Linear Mixed Model analysis was used to determine the association between microvascular volume (MV), VISA-A, and ESW-detection threshold for both symptomatic and asymptomatic Achilles tendons. RESULTS: There was a significant association between VISA-A and MV (B=-5.3, 95%CI=[-8.5; -2.0], P=0.0004), and between MV and symptom duration (B=-1.7, 95%CI=[-3.2; -5.0], P=0.023). No significant associations were found between power Doppler ultrasound and CEUS-based MV or between CEUS-based MV and ESW-detection threshold. In comparison with conventional power Doppler ultrasound, SMITM showed on average similar detection capacity for neovessels in the mid-portion of the Achilles tendon, whilst being superior for detecting neovessels within Kager's fat pad (t=3.46, 95%CI=[0.27; 1.03], P<0.005). CONCLUSIONS: Our results indicate that CEUS-based MV of the Achilles tendon is moderately associated with Achilles tendon symptoms. In accordance, CEUS-detected MV could be a novel target for treatment as it seems to be more sensitive than PDU and is correlated with symptoms. PMID- 29789267 TI - The effect of lower limb occlusion on recovery following sprint exercise in academy rugby players. AB - OBJECTIVES: The effects of vascular occlusion on recovery of physiological and neuromuscular markers over 24h, and hormonal reactivity to subsequent exercise were investigated. DESIGN: Counterbalanced, randomised, crossover. METHODS: Academy rugby players (n=24) completed six 50-m sprints (5-min inter-set recovery) before occlusion cuff application (thighs) and intermittent inflation to 171-266mmHg (Recovery) or 15mmHg (Con) for 12-min (two sets, 3-min repetitions, 3-min non-occluded reperfusion). Countermovement jumps, blood (lactate, creatine kinase), saliva (testosterone, cortisol), and perceptual (soreness, recovery) responses were measured before (baseline) and after (post, +2h, +24h) sprinting. Saliva was sampled after a 30-min resistance exercise session performed 24h after sprinting. RESULTS: Although sprinting (total: 40.0+/ 2.8s, p=0.238; average: 6.7+/-0.5s, p=0.674) influenced creatine kinase (p<0.001, +457.1+/-327.3MUL-1, at 24h), lactate (p<0.001, 6.8+/-2.3mmolL-1, post), testosterone (p<0.001, -55.9+/-63.2pgmL-1, at 2h) and cortisol (p<0.001, -0.3+/ 0.3MUgdL-1, at 2h) concentrations, countermovement jump power output (p<0.001, 409.6+/-310.1W; -5.4+/-3.4cm, post), perceived recovery (p<0.001, -3.0+/-2.3, post), and muscle soreness (p<0.001; 1.5+/-1.1, at 24h), vascular occlusion had no effect (all p>0.05) on recovery. In response to subsequent exercise performed 24h after vascular occlusion, testosterone increased pre-to-post-exercise (Recovery: p=0.031, 21.6+/-44.9pgmL-1; Con: p=0.178, 10.6+/-36.6pgmL-1) however Deltatestosterone was not significantly different (p=0.109) between conditions. CONCLUSIONS: Vascular occlusion had no effect on physiological or neuromuscular markers 2h or 24h after sprinting or in response to a physical stress test. PMID- 29789268 TI - Making Individual Prognoses in Psychiatry Using Neuroimaging and Machine Learning. AB - Psychiatric prognosis is a difficult problem. Making a prognosis requires looking far into the future, as opposed to making a diagnosis, which is concerned with the current state. During the follow-up period, many factors will influence the course of the disease. Combined with the usually scarcer longitudinal data and the variability in the definition of outcomes/transition, this makes prognostic predictions a challenging endeavor. Employing neuroimaging data in this endeavor introduces the additional hurdle of high dimensionality. Machine learning techniques are especially suited to tackle this challenging problem. This review starts with a brief introduction to machine learning in the context of its application to clinical neuroimaging data. We highlight a few issues that are especially relevant for prediction of outcome and transition using neuroimaging. We then review the literature that discusses the application of machine learning for this purpose. Critical examination of the studies and their results with respect to the relevant issues revealed the following: 1) there is growing evidence for the prognostic capability of machine learning-based models using neuroimaging; and 2) reported accuracies may be too optimistic owing to small sample sizes and the lack of independent test samples. Finally, we discuss options to improve the reliability of (prognostic) prediction models. These include new methodologies and multimodal modeling. Paramount, however, is our conclusion that future work will need to provide properly (cross-)validated accuracy estimates of models trained on sufficiently large datasets. Nevertheless, with the technological advances enabling acquisition of large databases of patients and healthy subjects, machine learning represents a powerful tool in the search for psychiatric biomarkers. PMID- 29789269 TI - Anterior Cingulate Cortex Glutamatergic Metabolites and Mood Stabilizers in Euthymic Bipolar I Disorder Patients: A Proton Magnetic Resonance Spectroscopy Study. AB - BACKGROUND: Bipolar disorder is a chronic and recurrent illness characterized by depressive and manic episodes. Proton magnetic resonance spectroscopy (1H-MRS) studies have demonstrated glutamate (Glu) system abnormalities in BD, but it is unclear how Glu varies among mood states and how medications modulate it. The objective of this study was to investigate the influence of mood stabilizers on anterior cingulate cortex Glu levels using 1H-MRS during euthymia. METHODS: One hundred twenty-eight bipolar I disorder (BDI) euthymic subjects and 80 healthy control subjects underwent 3T brain 1H-MRS imaging examination including acquisition of an anterior cingulate cortex single voxel (8 cm3) 1H-MRS, based on a point resolved spectroscopy (PRESS) sequence with an echo time of 80 ms and a repetition time of 1500 ms (BIPUSP MRS study). The Glu system was described by measuring Glu and the sum of Glu and glutamine (Glx) using creatine (Cre) as a reference. RESULTS: Euthymic BDI subjects presented with higher ratios of Glu/Cre and Glx/Cre compared to healthy control subjects. Glu/Cre ratios were lower among patients using anticonvulsants, while Glx/Cre did not differ between the two groups. Lithium, antipsychotics, and antidepressants did not influence Glu/Cre or Glx/Cre. CONCLUSIONS: We reported Glu/Cre and Glx abnormalities in the largest sample of euthymic BDI patients studied by 1H-MRS to date. Our data indicate that both Glu/Cre and Glx/Cre are elevated in BDI during euthymia regardless of medication effects, reinforcing the hypothesis of glutamatergic abnormalities in BD. Furthermore, we found an effect of anticonvulsants on Glu/Cre during euthymia, which might indicate a mechanism of mood stabilization in BD. PMID- 29789270 TI - Surplus fat rapidly increases fat oxidation and insulin resistance in lipodystrophic mice. AB - OBJECTIVE: Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' posits that the capacity to increase the size and number of adipocytes is finite and that when this limit is exceeded, fat accumulates in ectopic sites and leads to metabolic disease. METHODS: Here we studied the energetic and biochemical consequences of short-term (2-day) excess fat ingestion in a lipodystrophic (A ZIP/F-1) mouse model in which adipose capacity is severely restricted. RESULTS: In wildtype littermates, this acute exposure to high fat diets resulted in excess energy intake and weight gain without any significant changes in macronutrient oxidation rates, glucose, TAG, or insulin levels. In contrast, hyperphagic lipodystrophic mice failed to gain weight; rather, they significantly increased hepatic steatosis and fat oxidation. This response was associated with a significant increase in hyperglycemia, hyperinsulinemia, glucosuria, hypertriglyceridemia, and worsening insulin tolerance. CONCLUSIONS: These data suggest that when adipose storage reserves are saturated, excess fat intake necessarily increases fat oxidation and induces oxidative substrate competition which exacerbates insulin resistance resolving any residual energy surplus through excretion of glucose. PMID- 29789271 TI - Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity. AB - OBJECTIVE: To signal, FGF19 and FGF21 require co-receptor betaKlotho (KLB) to act in concert with FGF receptors, and yet there is appreciable variance in the C terminal sequences of these two novel metabolic hormones where binding is believed to be primary. We seek to determine the functional consequences for these amino acid differences and determine whether such information can be used to design high potency antagonists and agonists. METHODS: We employed a functional in vitro assay to identify C-terminal protein fragments capable of fully blocking KLB-mediated FGF19 and 21 receptor signaling. The key residues in each hormone responsible for support full bioactivity were identified through peptide-based Ala-scanning. Chemical optimization of the peptides was employed to increase their antagonistic potency. An optimized sequence as a substituted part of a full length FGF21 was assessed for enhanced FGFR/KLB-mediated agonism using tissue culture and obese mice. RESULTS: C-terminal FGF19 and FGF21 peptides of relatively short length were observed to potently inhibit the activity of these two hormones, in vitro and in vivo. These FGFs of different sequence also demonstrated a striking conservation of structural determinants to maintain KLB binding. A single C-terminal amino acid in FGF19 was observed to modulate relative activity through FGFR1 and FGFR4. The substitution of native FGF21 C terminal sequence with a peptide optimized for the highest antagonistic activity resulted in significantly enhanced FGF potency, as measured by in vitro signaling and improvements in metabolic outcomes in diet-induced obese mice. CONCLUSIONS: We report here the ability of short C-terminal peptides to bind KLB and function as antagonists of FGF19 and 21 actions. These proteins maintain high conservation of sequence in those residues central to KLB binding. An FGF21 chimeric protein possessing an optimized C-terminal sequence proved to be a super-agonist in delivery of beneficial metabolic effects in obese mice. PMID- 29789272 TI - PSOdisk is a reliable, intuitive instrument for the evaluation of psychological distress, which strongly correlates with DLQI: a preliminary study. AB - BACKGROUND: PSOdisk is a 10-item visual instrument, aimed at assessing the burden of disease in patients with psoriasis. OBJECTIVES: To compare PSOdisk with a scientifically validated questionnaire, the Dermatology Life Quality Index (DLQI), and asses both tools in relation to Psoriasis Severity Index (PASI) and patient acceptance. MATERIALS & METHODS: Fifty patients with cutaneous psoriasis and/or arthritic psoriasis were recruited. Correlation analysis between PSOdisk and DLQI was performed using Pearson's product-moment correlation coefficient. A multivariate linear regression was carried out to investigate the effect of PASI on PSOdisk and DLQI scores. In addition, we evaluated completion times as well as patient satisfaction for both PSOdisk and DLQI. RESULTS: PSOdisk and DLQI mean scores were 22.04 +/- 20.56 and 3.35 +/- 4.52, respectively. The mean value for PASI was 5.98 +/- 5.89 and for age was 55.88 +/- 14.09 years. The mean value of Cronbach's coefficient alpha was 0.88 for PSOdisk and 0.90 for DLQI, suggesting good reliability. A significant correlation was found between PSOdisk and PASI, and a statistically significant correlation between DLQI and PASI. Multivariate linear regression analysis demonstrated a statistically significant effect of PASI on both the DLQI score and PSOdisk score. CONCLUSIONS: PSOdisk demonstrates good correlation with DLQI and PASI, good patient satisfaction, and requires a short completion time. PMID- 29789273 TI - Insulin Resistance as Related to Psychiatric Disorders in Obese Children AB - Objective: The current study aimed to investigate psychiatric consequences of obesity and the relationship between componenets of the metabolic syndrome and psychiatric disorders in children. Our second aim was to elucidate which of the anthropometric parameters or metabolic components were most strongly associated with psychiatric disorders. Methods: The study included 88 obese and overweight children with a body mass index (BMI) greater than 85th percentile. The patients were evaluated for psychiatric disorders by a single child and adolescent psychiatrist. Forty patients diagnosed with psychiatric disorders and 48 patients with normal psychiatric evaluation were compared in terms of anthropometric and metabolic parameters. BMI, BMI-standard deviation score and BMI percentile, waist circumference, waist to hip ratio, blood pressure and pubertal stage of all patients were recorded. Fasting serum glucose, insulin, lipid profile and homeostatic model assessments of insulin resistance (HOMA-IR) were measured to evaluate the metabolic parameters. Serum and 24 hour urine cortisol levels were measured. Results: HOMA-IR in the group with psychiatric disorders was found to be significantly higher than in the group without psychiatric disorders (6.59+/ 3.36 vs 5.21+/-2.67; p=0.035). Other anthropometric measurements and metabolic parameters were not significantly different between the two groups. Conclusion: An understanding of the relationships between obesity related medical comorbidities and psychiatric pathologies is important to encourage patients and their families to make successful healthy lifestyle changes and for weight management in terms of appropriate treatment. PMID- 29789275 TI - Perceived Expressed Emotion, Emotional and Behavioral Problems and Self-Esteem in Obese Adolescents: A Case-Control Study AB - Objective: Obesity is a chronic disease which leads to medical and psychiatric complications. Family climate is a critical factor in the treatment of obesity and comorbid psychiatric disorders. In our study, perceived expressed emotion (EE), psychopathology, self-esteem and emotional and behavioural problems (BP) among obese adolescents were investigated and compared with their non-obese peers. Methods: The subjects were 49 obese adolescents and 47 non-obese adolescents served as the control group. All participants were requested to fill out the Socio-demographic Data Form, Shortened Level of Expressed Emotion Scale, Rosenberg Self-Esteem Scale, Strength and Difficulties Questionnaire-Adolescent Form. Results: In our study, obese adolescents showed a significant difference in perceived EE (p<0.001). Subscales of EE, such as Lack of Emotional Support (p<0.001), intrusiveness (p<0.001), irritability (p<0.001), self-esteem (p<0.001), emotional and BP (p<0.001), attention deficit-hyperactivity disorder (p<0.001), problems in peer relationships (p<0.001) and social skills (p<0.001) were significantly worse when compared with the control group. There was a strong relationship between EE and emotional and BP and self-esteem. Conclusion: The higher rate of perceived EE, psychopathology and low self-esteem among obese adolescents showed that obesity prevention and treatment are also crucial for good mental health in adolescents. The important role of the family in mental health of obese adolescents was emphasized. It was shown that identification of risk factors in childhood that promote obesity should be done so that targeted intervention and prevention programs can be developed. PMID- 29789276 TI - Novel Method to Efficiently Create an mHealth App: Implementation of a Real-Time Electrocardiogram R Peak Detector. AB - BACKGROUND: In parallel to the introduction of mobile communication devices with high computational power and internet connectivity, high-quality and low-cost health sensors have also become available. However, although the technology does exist, no clinical mobile system has been developed to monitor the R peaks from electrocardiogram recordings in real time with low false positive and low false negative detection. Implementation of a robust electrocardiogram R peak detector for various arrhythmogenic events has been hampered by the lack of an efficient design that will conserve battery power without reducing algorithm complexity or ease of implementation. OBJECTIVE: Our goals in this paper are (1) to evaluate the suitability of the MATLAB Mobile platform for mHealth apps and whether it can run on any phone system, and (2) to embed in the MATLAB Mobile platform a real time electrocardiogram R peak detector with low false positive and low false negative detection in the presence of the most frequent arrhythmia, atrial fibrillation. METHODS: We implemented an innovative R peak detection algorithm that deals with motion artifacts, electrical drift, breathing oscillations, electrical spikes, and environmental noise by low-pass filtering. It also fixes the signal polarity and deals with premature beats by heuristic filtering. The algorithm was trained on the annotated non-atrial fibrillation MIT-BIH Arrhythmia Database and tested on the atrial fibrillation MIT-BIH Arrhythmia Database. Finally, the algorithm was implemented on mobile phones connected to a mobile electrocardiogram device using the MATLAB Mobile platform. RESULTS: Our algorithm precisely detected the R peaks with a sensitivity of 99.7% and positive prediction of 99.4%. These results are superior to some state-of-the-art algorithms. The algorithm performs similarly on atrial fibrillation and non atrial fibrillation patient data. Using MATLAB Mobile, we ran our algorithm in less than an hour on both the iOS and Android system. Our app can accurately analyze 1 minute of real-time electrocardiogram signals in less than 1 second on a mobile phone. CONCLUSIONS: Accurate real-time identification of heart rate on a beat-to-beat basis in the presence of noise and atrial fibrillation events using a mobile phone is feasible. PMID- 29789274 TI - Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey AB - Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013 2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2+/-4.2 years and it was not significantly different between girls (9.0+/-4.1 years) and boys (9.4+/-4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58 9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study. PMID- 29789277 TI - Applicability of a Web-Based, Individualized Exercise Intervention in Patients With Liver Disease, Cystic Fibrosis, Esophageal Cancer, and Psychiatric Disorders: Process Evaluation of 4 Ongoing Clinical Trials. AB - BACKGROUND: In the primary and secondary prevention of civilization diseases, regular physical activity is recommended in international guidelines to improve disease-related symptoms, delay the progression of the disease, or to enhance postoperative outcomes. In the preoperative context, there has been a paradigm shift in favor of using preconditioning concepts before surgery. Web-based interventions seem an innovative and effective tool for delivering general information, individualized exercise recommendations, and peer support. OBJECTIVE: Our first objective was to assess feasibility of our Web-based interventional concept and analyze similarities and differences in a sustained exercise implementation in different diseases. The second objective was to investigate the overall participants' satisfaction with our Web-based concept. METHODS: A total of 4 clinical trials are still being carried out, including patients with esophageal carcinoma scheduled for oncologic esophagectomy (internet-based perioperative exercise program, iPEP, study), nonalcoholic fatty liver disease (hepatic inflammation and physical performance in patients with nonalcoholic steatohepatitis, HELP, study), depression (exercise for depression, EXDEP, study), and cystic fibrosis (cystic fibrosis online mentoring for microbiome, exercise, and diet, COMMED, study). During the intervention period, the study population had access to the website with disease-specific content and a disease-specific discussion forum. All participants received weekly, individual tailored exercise recommendations from the sports therapist. The main outcome was the using behavior, which was obtained by investigating the log-in rate and duration. RESULTS: A total of 20 participants (5 from each trial) were analyzed. During the intervention period, a regular contact and a consequent implementation of exercise prescription were easily achieved in all substudies. Across the 4 substudies, there was a significant decrease in log-in rates (P<.001) and log-in durations (P<.001) over time. A detailed view of the different studies shows a significant decrease in log-in rates and log-in durations in the HELP study (P=.004; P=.002) and iPEP study (P=.02; P=.001), whereas the EXDEP study (P=.58; P=.38) and COMMED study (P=.87; P=.56) showed no significant change over the 8 week intervention period. There was no significant change in physical activity within all studies (P=.31). Only in the HELP study, the physical activity level increased steadily over the period analyzed (P=.045). Overall, 17 participants (85%, 17/20) felt secure and were not scared of injury, with no major differences in the subtrials. CONCLUSIONS: The universal use of the Web-based intervention appears to be applicable across the heterogonous collectives of our study patients with regard to age and disease. Although the development of physical activity shows only moderate improvements, flexible communication and tailored support could be easily integrated into patients' daily routine. TRIAL REGISTRATION: iPEP study: ClinicalTrials.gov NCT02478996; https://clinicaltrials.gov/ct2/show/NCT02478996 (Archived by WebCite at http://www.webcitation.org/6zL1UmHaW); HELP study: ClinicalTrials.gov NCT02526732; http://www.webcitation.org/6zJjX7d6K (Archived by WebCite at http://www.webcitation.org/6Nch4ldcL); EXDEP study: ClinicalTrials.gov NCT02874833; https://clinicaltrials.gov/ct2/show/NCT02874833 (Archived by WebCite at http://www.webcitation.org/6zJjj7FuA). PMID- 29789278 TI - The Effectiveness of a Computer-Tailored E-Learning Program for Practice Nurses to Improve Their Adherence to Smoking Cessation Counseling Guidelines: Randomized Controlled Trial. AB - BACKGROUND: Improving practice nurses' (PN) adherence to smoking cessation counseling guidelines will benefit the quality of smoking cessation care and will potentially lead to higher smoking abstinence rates. However, support programs to aid PNs in improving their guideline uptake and adherence do not exist yet. OBJECTIVE: The aim of this study was to assess the effects of a novel computer tailored electronic learning (e-learning) program on PNs' smoking cessation guideline adherence. METHODS: A Web-based randomized controlled trial (RCT) was conducted in which an intervention group (N=147) with full access to the e learning program for 6 months was compared with a control group (N=122) without access. Data collection was fully automated at baseline and 6-month follow-up via online questionnaires, assessing PNs' demographics, work-related factors, potential behavioral predictors based on the I-Change model, and guideline adherence. PNs also completed counseling checklists to retrieve self-reported counseling activities for each consultation with a smoker (N=1175). To assess the program's effectiveness in improving PNs' guideline adherence (ie, overall adherence and adherence to individual counseling guideline steps), mixed linear and logistic regression analyses were conducted, thus accommodating for the smokers being nested within PNs. Potential effect moderation by work-related factors and behavioral predictors was also examined. RESULTS: After 6 months, 121 PNs in the intervention group (82.3%, 121/147) and 103 in the control group (84.4%, 103/122) completed the follow-up questionnaire. Mixed linear regression analysis revealed that counseling experience moderated the program's effect on PNs' overall guideline adherence (beta=.589; 95% CI 0.111-1.068; PHolm-Bonferroni =.048), indicating a positive program effect on adherence for PNs with a more than average level of counseling experience. Mixed logistic regression analyses regarding adherence to individual guideline steps revealed a trend toward moderating effects of baseline levels of behavioral predictors and counseling experience. More specifically, for PNs with less favorable scores on behavioral predictors (eg, low baseline self-efficacy) and high levels of counseling experience, the program significantly increased adherence. CONCLUSIONS: Results from our RCT showed that among PNs with more than average counseling experience, the e-learning program resulted in significantly better smoking cessation guideline adherence. Experienced PNs might have been better able to translate the content of our e-learning program into practically applicable counseling strategies compared with less experienced colleagues. Less favorable baseline levels of behavioral predictors among PNs possibly contributed to this effect, as there was more room for improvement by consulting the tailored content of the e learning program. To further substantiate the effectiveness of e-learning programs on guideline adherence by health care professionals (HCPs), it is important to assess how to support a wider range of HCPs. TRIAL REGISTRATION: Netherlands Trial Register NTR4436; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4436 (Archived by WebCite at http://www.webcitation.org/6zJQuSRq0). PMID- 29789279 TI - Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review. AB - BACKGROUND: Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. OBJECTIVE: The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. METHODS: To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. RESULTS: There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and medical record data continue to be insufficiently robust to provide estimates of the 90-90-90 targets for key populations. CONCLUSIONS: Current reliance on more active data collection processes, including key population-specific surveys, remains warranted until the quality and validity of passively collected routine program and medical record data for key populations is optimized. PMID- 29789280 TI - Factors Affecting Bone Mineral Density Among Snowy Region Residents in Japan: Analysis Using Multiple Linear Regression and Bayesian Network Model. AB - BACKGROUND: As the onset of osteoporosis leads to reduced activities of daily living and may result in patients being bedridden, efforts to prevent decreased bone density are necessary. Various studies on the relationship between sex, age, nutrients, and exercise habits and bone mineral density have been conducted to date. However, for snowy region residents, the magnitude of influence of various factors affecting bone mineral density and the influence level have not been clarified. OBJECTIVE: This study aimed to clarify the degree of influence and factors influencing bone mineral density based on survey results on health conditions and lifestyle habits in heavy snow areas. METHODS: A total of 354 citizens who visited a drugstore in the target area were included in a study that included using the brief-type self-administered diet history questionnaire on lifestyle and exercise habits. Height, weight, body composition, and bone densitometer values were analyzed using multiple regression to calculate their association with bone mineral density. In addition, a Bayesian network model was used to determine the influence level of each factor as a conditional probability. RESULTS: Multiple regression analysis revealed that age, sex, fracture, and calcium intake significantly influenced bone mineral density. In addition, the result of Bayesian network analysis suggested that age and sex affected bone mineral density, whereas nutrients and exercise habits might not have a direct impact. However, calcium intake and the T-score were significant factors affecting the presence or absence of fracture experiences, suggesting that adequate calcium intake is essential for preventing fractures. CONCLUSIONS: In the multiple regression analysis, age, sex, fracture, and calcium intake were selected as factors; however, in the Bayesian analysis, only age and sex affected bone mineral density while nutrients did not. In addition, the fact that calcium intake and the T-score were shown to affect bone fracture history suggests that calcium intake is an important measure that can prevent bone fractures. Overall, these results suggest that measures such as ensuring a bone fracture-free environment and providing nutritional advice for calcium intake can be effective in preventing bone loss. PMID- 29789282 TI - Internet Use, Depression, and Anxiety in a Healthy Adolescent Population: Prospective Cohort Study. AB - BACKGROUND: Psychiatric disorders, including conduct disturbances, substance abuse, and affective disorders, emerge in approximately 20% of adolescents. In parallel with the rise in internet use, the prevalence of depression among adolescents has increased. It remains unclear whether and how internet use impacts mental health in adolescents. OBJECTIVE: We assess the association between patterns of internet use and two mental health outcomes (depression and anxiety) in a healthy adolescent population. METHODS: A total of 126 adolescents between the ages of 12 and 15 years were recruited. Participants reported their typical computer and internet usage patterns. At baseline and one-year follow-up, they completed the Beck Depression Index for primary care (BDI-PC) and the Beck Anxiety Inventory for Primary Care (BAI-PC). Individual linear regressions were completed to determine the association between markers of internet use at baseline and mental health outcomes at one-year follow-up. All models controlled for age, gender, and ethnicity. RESULTS: There was an inverse correlation between minutes spent on a favorite website per visit and BAI-PC score. No association was found between internet use and BDI-PC score. CONCLUSIONS: There is no relationship between internet use patterns and depression in adolescents, whereas internet use may mitigate anxiety in adolescents with higher levels of baseline anxiety. PMID- 29789283 TI - Safety of medicines delivered by homecare companies. PMID- 29789281 TI - Internet and Social Media Access Among Youth Experiencing Homelessness: Mixed Methods Study. AB - BACKGROUND: Youth experiencing homelessness are at a risk for a variety of adverse outcomes. Given the widespread use of the internet and social media, these new technologies may be used to address their needs and for outreach purposes. However, little is known about how this group uses these resources. OBJECTIVE: This study investigated how homeless adolescents use these technologies for general and health-related purposes, whether the scope of their use changes with housing status, and their interest in a website dedicated to youth experiencing homelessness. METHODS: A convenience sample of youth aged 18 to 21 years was recruited from a youth-specific homeless shelter. All participants completed a 47-item survey, with 10 individuals completing a semistructured interview. Descriptive statistics, exact testing, logistic regression, and generalized estimating equation modeling was performed for quantitative data analysis. Interviews were transcribed verbatim, and NVivo 10 (QSR International) was employed to facilitate double coding and thematic analysis. RESULTS: A total of 87 participants completed the survey with a mean age of 19.4 (SD 1.1) years. While experiencing homelessness, 56% (49/87) accessed the internet at least once a day, with 86% (75/87) accessing once a week. Access to a smartphone was associated with a 3.03 greater odds of accessing the internet and was the most frequently used device (66% of participants, 57/87). While experiencing homelessness, subjects reported a 68% decreased odds in internet access frequency (odds ratio [OR] 0.32, P<.001), 75% decreased odds in spending greater amounts of time on the internet (OR 0.25, P<.001), and an 87% decreased odds of social media use (OR 0.13, P=.01). Ten participants completed the semistructured interview. Several themes were identified, including (1) changes in internet behaviors while experiencing homelessness, (2) health status as a major concern and reason for Internet use, and (3) interest in a website dedicated to youth experiencing homelessness. While experiencing homelessness, participants indicated their behaviors were more goal-oriented and less focused on leisure or entertainment activities. CONCLUSIONS: While homeless youth experience changes in the frequency, amount of time, and specific uses of the internet and social media, study participants were able to access the internet regularly. The internet was used to search health-related topics. Given the importance of smartphones in accessing the internet, mobile-optimized websites may be an effective method for reaching this group. PMID- 29789284 TI - A home for patient-oriented research. PMID- 29789285 TI - "All my relations": experiences and perceptions of Indigenous patients connecting with Indigenous Elders in an inner city primary care partnership for mental health and well-being. AB - BACKGROUND: Mental health services in urban settings generally have not been adapted to serve the needs of Indigenous patients. We explored how patients' encounters with Indigenous Elders affected their overall mental health and well being to identify therapeutic mechanisms underlying improvement. METHODS: We conducted qualitative interviews of participants enrolled in a 6-month prospective mixed-methods evaluation of a program for mental health and well being that featured the inclusion of Elders in the direct care of Indigenous patients in an inner city primary care clinic. Individual semistructured interviews were conducted to explore patients' experiences and perceptions of their participation in the Elders program. RESULTS: We included 37 participants from at least 20 different First Nations. All but 1 participant described substantial benefits from their encounters with Elders, and none reported being negatively affected. Five overarching themes were identified: experiencing healing after prolonged periods of seeking and desperation; strengthening cultural identity and belonging; developing trust and opening up; coping with losses; and engaging in ceremony and spiritual dimensions of care as a resource for hope. INTERPRETATION: Our evaluation illustrates that the Elders program was perceived by participants to have a broad range of positive impacts on their care and well-being. Although this study was based on experiences at a single urban clinic, these findings support the Truth and Reconciliation Commission of Canada's calls to action regarding the inclusion of Elders as a strategy to improve care of Indigenous patients in Canadian health care systems. PMID- 29789286 TI - Improving health research among Indigenous Peoples in Canada. PMID- 29789287 TI - Lyme carditis and atrioventricular block. PMID- 29789288 TI - Porphyria cutanea tarda presenting as milia and blisters. PMID- 29789289 TI - Effects of helmet use on costs of motorcycle crashes. PMID- 29789290 TI - Response to: "Some patients with chronic pain need low-dose opioid therapy for survival and quality of life". PMID- 29789291 TI - Is Ontario adding drug prices to EMRs? PMID- 29789292 TI - New fines pose financial catch-22 for Ontario long-term care. PMID- 29789293 TI - Major gaps in supports for medical trainees with disabilities. PMID- 29789294 TI - Public health in the 21st century: Governance for a healthy, just and sustainable future. PMID- 29789295 TI - Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks. AB - Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs. We used the t-distributed stochastic neighbor embedding (t-SNE) method to identify PTM clusters and then integrated each with known protein protein interactions (PPIs) to elucidate functional cell signaling pathways. The CFN identified known and previously unknown cell signaling pathways in lung cancer cells that were not present in normal lung epithelial tissue. In various proteins modified by more than one type of PTM, the incidence of those PTMs exhibited inverse relationships, suggesting that molecular exclusive "OR" gates determine a large number of signal transduction events. We also showed that the acetyltransferase EP300 appears to be a hub in the network of pathways involving different PTMs. In addition, the data shed light on the mechanism of action of geldanamycin, an HSP90 inhibitor. Together, the findings reveal that cell signaling pathways mediated by acetylation, methylation, and phosphorylation regulate the cytoskeleton, membrane traffic, and RNA binding protein-mediated control of gene expression. PMID- 29789296 TI - Tuning ITAM multiplicity on T cell receptors can control potency and selectivity to ligand density. AB - The T cell antigen receptor (TCR) recognizes peptides from pathogenic proteins bound in the major histocompatibility complex (MHC). To convert this binding event into downstream signaling, the TCR complex contains immunoreceptor tyrosine based activation motifs (ITAMs) that act as docking sites for the cytoplasmic tyrosine kinase ZAP-70. Unique among antigen receptors, the TCR complex uses 10 ITAMs to transduce peptide-MHC binding to the cell interior. Using synthetic, drug-inducible receptor-ligand pairs, it was found that greater ITAM multiplicity primarily enhanced the efficiency with which ligand binding was converted into an intracellular signal. This manifested as an increase in the fraction of cells that became activated in response to antigen, and a more synchronous initiation of TCR-proximal signaling, rather than direct amplification of the intracellular signals. Exploiting these findings, the potency and selectivity of chimeric antigen receptors targeted against cancer were substantially enhanced by modulating the number of encoded ITAMs. PMID- 29789298 TI - Challenge anti-migrant policies with evidence, doctors are told. PMID- 29789299 TI - David Oliver: Are comparisons between acute healthcare and the aviation industry invidious? PMID- 29789300 TI - Teamwork on Rounds on an Inpatient Ward Team: An Ethnographic Study. AB - BACKGROUND AND OBJECTIVES: Pediatric hospitalists are expected to be adept at effective teamwork; yet, studies in which researchers describe teamwork practices in general pediatric inpatient settings are lacking. Our aim in this study was to examine the roles that general pediatric team members assume in real-life settings and how team members conduct teamwork practices on family-centered rounds. METHODS: In the ethnographic tradition, we observed a general pediatric team on a hospitalist service, focusing on family-centered rounds, and conducted in-depth interviews with interns, senior residents, and faculty. We collected data in the form of field notes from observations and transcribed interviews and used constant comparison methods to create codes and generate themes. We used Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) as an analytic lens and organizing framework. RESULTS: Communication occurred in both structured and unstructured ways. Situation monitoring happened during routines, such as running the list, and led to creating a plan of patient care through shared decision-making. Some leadership characteristics were not exclusive to 1 team member. Finally, mutual support occurred through task completion and empowering learners; for example, attending physicians empowered senior residents, who also helped interns. CONCLUSIONS: Our findings aligned with some, but not all, teamwork principles from TeamSTEPPS; misalignment may be due to contextual factors, such as the need to provide medical education and the development of grassroots routines (eg, running the list). Context is a key consideration when developing interventions to enhance teamwork on inpatient medical wards. PMID- 29789297 TI - The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms. AB - Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the alpha and alpha-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the delta and epsilon isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1gamma1, CK1gamma2, and CK1gamma3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain. PMID- 29789301 TI - ORBITA2. PMID- 29789303 TI - #Me_Who: Anatomy of Scholastic, Leadership, and Social Isolation of Underrepresented Minority Women in Academic Medicine. AB - In academic medicine, under-represented minority women physician-scientists (URMWP)* are uncommon, particularly in leadership positions. Data from the American Association of Medical Colleges (AAMC) show that among internal medicine chairs, there are 12 Asian males, 10 African/American (blacks; 9 men), 7 Hispanics (2 females) and 137 whites (21 females). In the top 40 ranked cardiology programs, there are no female cardiology chiefs, whereas there are at least 10, 2, 1 and 24 Asian, black, Hispanic and white males respectively. There are more URMWP than URM males, yet URMWP are less likely to be professors and occupy leadership positions in academia. Specifically, among United States medical school faculty, relative proportions at assistant, associate and full professor levels according to race/ethnicity and gender have remained essentially unchanged over the past 20 years. AAMC information demonstrates that only 11%, 9%, 11% and 24% of Asian, black, Hispanic and white women are full professors compared with 21%, 18%, 19% and 36% of Asian, black, Hispanic and white men. Additionally, while there are representative proportions of women and Asians at the lowest faculty levels, they have not equitably progressed in academic medicine, likely reflecting discrimination and structural/organizational barriers that are also applicable to black and Hispanic females1. PMID- 29789302 TI - Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease. AB - BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69+/-0.16 and 0.76+/-0.22, respectively; 97% had >=1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( Pinteraction=0.318) or iFR ( Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( Pinteraction<0.00001) and decreasing iFR ( Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( Pinteraction=0.849) or iFR ( Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( Pinteraction=0.693) nor iFR ( Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593. PMID- 29789304 TI - Neuroimaging findings in Menkes disease: a rare neurodegenerative disorder. AB - Menkes disease is a rare neurodegenerative metabolic disease with a reported incidence of 1 per 300 000 live births. It occurs due to mutations in ATP7A gene located on X-chromosome leading to deficiency of several copper-containing enzymes. The patient presents with history of neuroregression with characteristic kinky hair. MRI is the imaging modality of choice. Characteristic imaging findings are: bilateral subdural hygromas, cerebral and cerebellar atrophy, white matter changes and tortuous intracranial vessels on angiography. The rarity of this condition prompted us to report this case of Menkes disease along with the characteristic neuroimaging findings and brief review of literature. PMID- 29789306 TI - Chronic Madura foot: mycetoma and/or Actinomyces spp or actinomycosis. AB - A 58-year-old agricultural worker from a remote Western province farming community in Saudi Arabia presented with a 2-year history of right plantar foot soft tissue mass. According to the patient, the swelling had gradually increased in size over a few years, but it was painless and thus had not restricted him from continuing to farm until the lesion started to affect mobility. An MRI, microbiology and histopathology reported a rare infectious agent-Actinomyces spp, otherwise referred to as Madura foot. Three-dimensional CT aided in a preoperative surgical plan which included mass excision/debulking for this challenging lesion. Full eradication was not possible, and the patient required prolonged anti-infective therapy (>6 months) along with close surveillance to map resolution of infective symptoms. PMID- 29789305 TI - Ro-positive interstitial lung disease treated with cyclophosphamide. AB - Interstitial lung disease (ILD) comprises a spectrum of conditions involving inflammation and/or fibrosis of the alveolar wall causing limitation in gaseous exchange. Treatment varies depending on the underlying ILD. We describe the case of a woman presenting with a productive cough who was diagnosed with community acquired pneumonia. While on the ward she developed type-1 respiratory failure requiring continuous positive airway pressure and intensive care unit admission. Failing to respond to targeted antimicrobials she was investigated by chest high resolution CT and autoantibody screen to identify non-infective causes of her respiratory signs and symptoms. These demonstrated diffuse ground-glass change with peripheral honeycombing in keeping with fibrosis and alveolitis alongside high titres of anti-SS-A/Ro antibodies. She was managed with reducing course of steroids and immunosuppression with cyclophosphamide. The rational of long-term immunosuppression was based on a presumed diagnosis of lung-dominant connective tissue disease, a disease concept proposed in contemporary medical literature. PMID- 29789307 TI - Overcoming overuse: the way forward is not standing still-an essay by Steven Woloshin and Lisa M Schwartz. PMID- 29789309 TI - GPs have been Luddites for too long and must embrace new technology. PMID- 29789308 TI - High-throughput discovery of functional disordered regions. PMID- 29789311 TI - FDA Tackles Underage E-cigarette Use. AB - In recent weeks, the FDA has taken steps to address underage use of e-cigarettes: The agency has identified and warned retailers selling to minors, issued warning letters to companies selling e-cigarette cartridges in adolescent-appealing packaging, and requested information from e-cigarette companies. The steps are part of the FDA's ongoing effort to prevent middle- and high-school students from using e-cigarette products. PMID- 29789310 TI - CLERK is a novel receptor kinase required for sensing of root-active CLE peptides in Arabidopsis. AB - CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides are secreted endogenous plant ligands that are sensed by receptor kinases (RKs) to convey environmental and developmental inputs. Typically, this involves an RK with narrow ligand specificity that signals together with a more promiscuous co-receptor. For most CLEs, biologically relevant (co-)receptors are unknown. The dimer of the receptor like protein CLAVATA 2 (CLV2) and the pseudokinase CORYNE (CRN) conditions perception of so-called root-active CLE peptides, the exogenous application of which suppresses root growth by preventing protophloem formation in the meristem. clv2 as well as crn null mutants are resistant to root-active CLE peptides, possibly because CLV2-CRN promotes expression of their cognate receptors. Here, we have identified the CLE-RESISTANT RECEPTOR KINASE (CLERK) gene, which is required for full sensing of root-active CLE peptides in early developing protophloem. CLERK protein can be replaced by its close homologs, SENESCENCE ASSOCIATED RECEPTOR-LIKE KINASE (SARK) and NSP-INTERACTING KINASE 1 (NIK1). Yet neither CLERK nor NIK1 ectodomains interact biochemically with described CLE receptor ectodomains. Consistently, CLERK also acts genetically independently of CLV2-CRN We, thus, have discovered a novel hub for redundant CLE sensing in the root. PMID- 29789312 TI - Development of Diagnostic SNP Markers To Monitor Hybridization Between Sika Deer (Cervus nippon) and Wapiti (Cervus elaphus). AB - Sika deer (Cervus Nippon) and wapiti (Cervus elaphus) are closely related species and their hybridization can result in significant allele-shift of their gene pool. Additive genetic effects and putative heterotic effects of their hybridization on growth performance could confer considerable economic advantage in deer farming. Here, we used double-digest restriction site-associated DNA sequencing technology (ddRAD-seq) and detected ~320,000 genome-wide SNPs from 30 captive individuals: 7 sika deer, 6 wapiti and 17 F1 hybrids (reciprocal cross). By screening observed heterozygosity of each SNP across four taxonomic groups, we report for the first time a resource of 2,015 putative diagnostic SNP markers (species-specific SNPs for sika deer and wapiti), which can be used to design tools for assessing or monitoring the degree of hybridization between sika deer and wapiti. These ddRAD-seq data and SNP datasets are also valuable resources for genome-wide studies, including trait discovery for breeders of domestic deer. PMID- 29789315 TI - Quinoline-3-carboxamides such as tasquinimod are not specific inhibitors of S100A9. PMID- 29789313 TI - BLAST-XYPlot Viewer: A Tool for Performing BLAST in Whole-Genome Sequenced Bacteria/Archaea and Visualize Whole Results Simultaneously. AB - One of the most commonly used tools to compare protein or DNA sequences against databases is BLAST. We introduce a web tool that allows the performance of BLAST searches of protein/DNA sequences in whole-genome sequenced bacteria/archaea, and displays a large amount of BLAST-results simultaneously. The circular bacterial replicons are projected as horizontal lines with fixed length of 360, representing the degrees of a circle. A coordinate system is created with length of the replicon along the x-axis and the number of replicon used on the y-axis. When a query sequence matches with a gene/protein of a particular replicon, the BLAST-results are depicted as an "x,y" position in a specially adapted plot. This tool allows the visualization of the results from the whole data to a particular gene/protein in real time with low computational resources. PMID- 29789316 TI - Oral ivermectin for the treatment of head lice infestation. AB - PURPOSE: Published literature describing the use of oral ivermectin for the treatment of head lice infestation is reviewed. SUMMARY: In the United States and globally, head lice infestation, or pediculosis capitis, remains a public health issue with both social and medical implications. Treatment with oral or topical medications is typically required for head lice eradication. Resistance to traditional topical therapies for head lice infestation is increasing, creating a need for consideration of additional treatment options. A growing body of data describing the potential role of oral ivermectin for the treatment or prevention of head lice infestation is available. A literature search identified 5 clinical trials that evaluated safety and/or effectiveness outcomes of oral ivermectin use as an alternative to malathion, other topical prescription medications, and traditional, nonprescription remedies; those studies were conducted in various parts of the world (e.g., Australia, Brazil, Mexico, Egypt) and likely involved varying types and degrees of lice resistance. Clinical research findings to date, while not consistently robust, suggest that oral ivermectin is comparable or superior in effectiveness to other topical treatment options for head lice infestation while being well tolerated and favorably perceived by patients and caretakers. CONCLUSION: Oral ivermectin is an option for the treatment of head lice infestation, especially in individuals who have experienced a treatment failure. Published evidence from clinical trials indicates that oral ivermectin is as effective as currently available topical treatments. PMID- 29789314 TI - Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase. AB - The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers including acute myeloid leukemia (AML). Here we show that the antileukemic activity of the chemotherapeutic nucleoside analogs hydroxyurea and gemcitabine was significantly potentiated by ATR inhibition via a mechanism involving ribonucleotide reductase (RNR) abrogation and inhibition of replication fork progression. When administered in combination with gemcitabine, an inhibitor of the M1 RNR subunit, the ATR inhibitor VX-970, eradicated disseminated leukemia in an orthotopic mouse model, eliciting long term survival and effective cure. These data identify a synergistic interaction between ATR inhibition and RNR loss that will inform the deployment of small molecule inhibitors for the treatment of AML and other hematologic malignancies. PMID- 29789317 TI - Nonprescription availability of the opioid antagonist naloxone. PMID- 29789318 TI - Impact of a pharmacist-physician collaborative care model on patient outcomes and health services utilization. AB - PURPOSE: The impact of a pharmacist-physician collaborative care model on patient outcomes and health services utilization is described. METHODS: Six hospitals from the Carilion Clinic health system in southwest Virginia, along with 22 patient-centered medical home (PCMH) practices affiliated with Carilion Clinic, participated in this project. Eligibility criteria included documented diagnosis of 2 or more of the 7 targeted chronic conditions (congestive heart failure, hypertension, hyperlipidemia, diabetes mellitus, asthma, chronic obstructive pulmonary disease, and depression), prescriptions for 4 or more medications, and having a primary care physician in the Carilion Clinic health system. A total of 2,480 evaluable patients were included in both the collaborative care group and the usual care group. The primary clinical outcomes measured were the absolute change in values associated with diabetes mellitus, hypertension, and hyperlipidemia management from baseline within and between the collaborative care and usual care groups. RESULTS: Significant improvements (p < 0.01) in glycosylated hemoglobin, blood pressure, low-density-lipoprotein cholesterol, and total cholesterol were observed in the collaborative care group compared with the usual care group. Hospitalizations declined significantly in the collaborative care group (23.4%), yielding an estimated cost savings of $2,619 per patient. The return on investment (net savings divided by program cost) was 504%. CONCLUSION: Inclusion of clinical pharmacists in this physician-pharmacist collaborative care based PCMH model was associated with significant improvements in patients' medication-related clinical health outcomes and a reduction in hospitalizations. PMID- 29789319 TI - Faecal immunochemical tests have the potential for correctly ruling out colorectal cancer in symptomatic patients. PMID- 29789320 TI - Intensive versus standard blood pressure treatment improves cardiovascular outcomes without any difference in patient-reported outcomes. PMID- 29789321 TI - Introducing the informed health choices project to Ireland. PMID- 29789322 TI - A missing piece: the spiny mouse and the puzzle of menstruating species. AB - We recently discovered the first known menstruating rodent. With the exception of four bats and the elephant shrew, the common spiny mouse (Acomys cahirinus) is the only species outside the primate order to exhibit menses. There are few widely accepted theories on why menstruation developed as the preferred reproductive strategy of these select mammals, all of which reference the evolution of spontaneous decidualisation prior to menstrual shedding. Though menstruating species share several reproductive traits, there has been no identifiable feature unique to menstruating species. Such a feature might suggest why spontaneous decidualisation, and thus menstruation, evolved in these species. We propose that a >=3-fold increase in progesterone during the luteal phase of the reproductive cycle is a unique characteristic linking menstruating species. We discuss spontaneous decidualisation as a consequence of high progesterone, and the potential role of prolactin in screening for defective embryos in these species to aid in minimising implantation of abnormal embryos. We further explore the possible impact of nutrition in selecting species to undergo spontaneous decidualisation and subsequent menstruation. We summarise the current knowledge of menstruation, discuss current pre-clinical models of menstruation and how the spiny mouse may benefit advancing our understanding of this rare biological phenomenon. PMID- 29789323 TI - The emerging connections between IGF1, the intestinal microbiome, Lactobacillus strains and bone growth. AB - In most animal species, postnatal growth is controlled by conserved insulin/insulin-like growth factor (IGF) signaling. In mammals, juvenile growth is characterized by a longitudinal bone growth resulting from the ossification of the growth plate. This ossification is under IGF1 influence through endocrine and paracrine mechanisms. Moreover, the nutritional status has been largely described as an important factor influencing the insulin/insulin-like growth factor signaling. It is now well established that the gut microbiota modulates the nutrient availability of its host. Hence, studies of the interaction between nutritional status, gut microbiota and bone growth have recently emerged. Here, we review recent findings using experimental models about the impact of gut bacteria on the somatotropic axis and its consequence on the bone growth. We also discuss the perspectives of these studies in opening an entire field for clinical interventions. PMID- 29789324 TI - Smoking and Cutaneous Melanoma: Findings from the QSkin Sun and Health Cohort Study. AB - Background: Previous studies suggest that smokers have lower risks of cutaneous melanoma than nonsmokers, but data from population-based prospective studies are scarce. We investigated associations between smoking and melanoma in a cohort study purpose-designed to investigate skin cancer outcomes.Methods: Participants with no prior history of melanoma (n = 38,697) completed a risk factor survey at baseline (2011). Patients were followed through linkage to the cancer registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between smoking (including intensity, duration, time since quitting) and melanoma using multivariate Cox proportional hazards regression, accounting for death as a competing event.Results: During a mean follow-up of 3.5 years, invasive melanomas developed in 247 participants. Compared with never smokers, former smokers (but not current smokers) had lower risks of invasive melanoma (HR 0.76; 95% CI, 0.57-1.01). Among former smokers, risks were lower with greater quantity of cigarettes smoked (HR 0.75; 95% CI, 0.56-0.98 per 10 cigarettes/day). No association was observed with duration of smoking while longer time since quitting was associated with a relative risk of melanoma that was not significantly different from the null (HR 1.18; 95% CI, 0.91-1.51, for every 10 years since quitting).Conclusions: We observed complex associations between smoking and melanoma, with some suggestion that former smokers had lower risks than never or current smokers. The apparent inverse association among former smokers may be due to residual confounding, although surveillance bias or biological effects cannot be excluded entirely.Impact: Smoking does not increase the risk of cutaneous melanoma. Cancer Epidemiol Biomarkers Prev; 27(8); 874-81. (c)2018 AACR. PMID- 29789326 TI - Hepatocellular Carcinoma Outcome Is Predicted by Expression of Neuronal Calcium Sensor 1. AB - Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer related death worldwide. There is an urgent demand for prognostic biomarkers that facilitate early tumor detection, as the incidence of HCC has tripled in the United States in the last three decades. Biomarkers to identify populations at risk would have significant impact on survival. We recently found that expression of Neuronal Calcium Sensor 1 (NCS1), a Ca2+-dependent signaling molecule, predicted disease outcome in breast cancer, but its predictive value in other cancer types is unknown. This protein is potentially useful because increased NCS1 regulates Ca2+ signaling and increased Ca2+ signaling is a hallmark of metastatic cancers, conferring cellular motility and an increasingly aggressive phenotype to tumors.Methods: We explored the relationship between NCS1 expression levels and patient survival in two publicly available liver cancer cohorts and a tumor microarray using data mining strategies.Results: High NCS1 expression levels are significantly associated with worse disease outcome in Asian patients within these cohorts. In addition, a variety of Ca2+-dependent and tumor growth promoting genes are transcriptionally coregulated with NCS1 and many of them are involved in cytoskeleton organization, suggesting that NCS1 induced dysregulated Ca2+ signaling facilitates cellular motility and metastasis.Conclusions: We found NCS1 to be a novel biomarker in HCC. Furthermore, our study identified a pharmacologically targetable signaling complex that can influence tumor progression in HCC.Impact: These results lay the foundation for using NCS1 as a prognostic biomarker in prospective cohorts of HCC patients and for further functional assessment of the characterized signaling axis. Cancer Epidemiol Biomarkers Prev; 27(9); 1091-100. (c)2018 AACR. PMID- 29789325 TI - Genomic-Epidemiologic Evidence That Estrogens Promote Breast Cancer Development. AB - Background: Estrogens are a prime risk factor for breast cancer, yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Because estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17beta estradiol (E2), and the estrogen receptor ESR1 (ERalpha). Because different types of tumors are characterized by unique sets of cancer driver genes, we also argue that the fraction of driver genes regulated by E2-ESR1 is lower in malignancies not associated with estrogens, e.g., acute myeloid leukemia (AML).Methods: We performed a literature search of each driver gene to determine its E2-ESR1 regulation.Results: Fifty-three of the 82 driver genes (64.6%) identified in breast cancers showed evidence of E2-ESR1 regulation. In contrast, only 19 of 54 mutated driver genes (35.2%) identified in AML were linked to E2-ESR1. Among the 916 driver mutations found in breast cancers, 813 (88.8%) were linked to E2-ESR1 compared with 2,046 of 3,833 in AML (53.4%).Conclusions: Risk assessment revealed that mutations in estrogen-regulated genes are much more likely to be associated with elevated breast cancer risk, while mutations in unregulated genes are more likely to be associated with AML.Impact: These results increase the plausibility that estrogens promote breast cancer development. Cancer Epidemiol Biomarkers Prev; 27(8); 899-907. (c)2018 AACR. PMID- 29789328 TI - BAPIO calls for single visa route for non-EU doctors to boost NHS workforce and prevent brain drain. PMID- 29789327 TI - Antidepressant Use and Risk of Colorectal Cancer in the Women's Health Initiative. AB - Background: Some prior studies have reported reduced colorectal cancer risk among individuals using antidepressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Yet most studies have not considered the potential role of depression or other confounders in their analyses.Methods: We utilized prospectively collected data from 145,190 participants in the Women's Health Initiative, among whom 2,580 incident colorectal cancer cases were diagnosed. Antidepressant use and depressive symptoms were assessed at baseline and follow up study visits. Cox proportional hazards regression models with adjustment for depressive symptoms and other covariates were utilized to estimate HRs and 95% confidence intervals (CIs) for associations between antidepressant use and colorectal cancer.Results: Antidepressant use was reported by 6.9% of participants at baseline, with SSRIs the most common class of antidepressant used. In multivariable analyses, including adjustment for depressive symptomology, we observed no statistically significant association between antidepressant use overall (HR = 0.90; 95% CI, 0.75-1.09) or with SSRIs specifically (HR = 1.08; 95% CI, 0.85-1.37) and colorectal cancer risk. A borderline significant reduction in colorectal cancer risk was observed for use of tricyclic antidepressants (HR = 0.76; 95% CI, 0.56-1.04). Severe depressive symptoms were independently associated with a 20% increased risk of colorectal cancer (HR = 1.21; 95% CI, 1.09-1.48). Results were similar for separate evaluations of colon and rectal cancer.Conclusions: We observed no evidence of an association between antidepressant use, overall or by therapeutic class, and colorectal cancer risk.Impact: These results suggest that antidepressants may not be useful as chemopreventive agents for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 892-8. (c)2018 AACR. PMID- 29789329 TI - New approaches to WHO financing: the key to better health. PMID- 29789330 TI - Trudeau calls for inquiry after Canadian doctor is shot in Gaza. PMID- 29789331 TI - Sugar in food: critics urge tougher regulation as industry fails to meet reduction target. PMID- 29789332 TI - Elevated Potassium Levels in Patients With Congestive Heart Failure: Occurrence, Risk Factors, and Clinical Outcomes: A Danish Population-Based Cohort Study. AB - BACKGROUND: Data on the true burden of hyperkalemia in patients with heart failure (HF) in a real-world setting are limited. METHODS AND RESULTS: Incidence rates of hyperkalemia (first blood test with a potassium level >5.0 mmol/L) in primary or hospital care were assessed in a population-based cohort of patients with incident HF diagnoses in northern Denmark from 2000 to 2012. Risk factors and clinical outcomes were compared in patients with HF with versus without hyperkalemia. Of 31 649 patients with HF, 39% experienced hyperkalemia (mean follow-up, 2.2 years). Risks of experiencing a second, third, or fourth event were 43%, 54%, and 60%, respectively. Among patients with HF with stage 3A, 3B, 4, or 5 kidney dysfunction, 26%, 35%, 44%, and 48% experienced hyperkalemia within the first year. Important hyperkalemia risk factors included chronic kidney disease (prevalence ratio, 1.46; 95% confidence interval [CI], 1.43-1.49), diabetes mellitus (prevalence ratio, 1.38; 95% CI, 1.32-1.45), and spironolactone use (prevalence ratio, 1.48; 95% CI, 1.42-1.54). In patients with HF who developed hyperkalemia, 53% had any acute-care hospitalization 6 months before the hyperkalemia event, increasing to 74% 6 months after hyperkalemia (before after risk ratio, 1.41; 95% CI, 1.38-1.44). Compared with matched patients with HF without hyperkalemia, adjusted 6-month hazard ratios in patients with hyperkalemia were 2.75-fold (95% CI, 2.65-2.85) higher for acute-care hospitalization and 3.39-fold (95% CI, 3.19-3.61) higher for death. CONCLUSIONS: Almost 4 in 10 patients with HF develop hyperkalemia, and many patients have recurrent hyperkalemia episodes. Hyperkalemia risk is strongly associated with degree of reduced kidney function and use of spironolactone. Hyperkalemia is associated with severe clinical outcomes and death in HF. PMID- 29789333 TI - Hyperkalemia in Heart Failure: Probably Not O"K". PMID- 29789334 TI - X-Ray Exposure in Cardiac Electrophysiology: A Retrospective Analysis in 8150 Patients Over 7 Years of Activity in a Modern, Large-Volume Laboratory. AB - BACKGROUND: Only a few studies have systematically evaluated fluoroscopy data of electrophysiological and device implantation procedures. Aims of this study were to quantify ionizing radiation exposure for electrophysiological/device implantation procedures in a large series of patients and to analyze the x-ray exposure trend over years and radiation exposure in patients undergoing atrial fibrillation ablation considering different technical aspects. METHODS AND RESULTS: We performed a retrospective analysis of all electrophysiological/device implantation procedures performed during the past 7 years in a modern, large volume laboratory. We reported complete fluoroscopy data on 8150 electrophysiological/device implantation procedures (6095 electrophysiological and 2055 device implantation procedures); for each type of procedure, effective dose and lifetime attributable risk of cancer incidence and mortality were calculated. Over the 7-year period, we observed a significant trend reduction in fluoroscopy time, dose area product, and effective dose for all electrophysiological procedures (P<0.001) and a not statistically significant trend reduction for device implantation procedures. Analyzing 2416 atrial fibrillation ablations, we observed a significant variability of fluoroscopy time, dose area product and effective dose among 7 different experienced operators (P<0.0001) and a significant reduction of fluoroscopy use over time (P<0.0001) for all of them. Considering atrial fibrillation ablation techniques, fluoroscopy time was not different (P = 0.74) for radiofrequency catheter ablation in comparison with cryoablation, though cryoablation was still associated with higher dose area product and effective dose values (P<0.001). CONCLUSIONS: Electrophysiological procedures involve a nonnegligible x-ray use, leading to an increased risk of malignancy. Awareness of radiation-related risk, together with technological advances, can successfully optimize fluoroscopy use. PMID- 29789335 TI - Prediction of Thrombotic and Bleeding Events After Percutaneous Coronary Intervention: CREDO-Kyoto Thrombotic and Bleeding Risk Scores. AB - BACKGROUND: Prediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention. METHODS AND RESULTS: We developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) and NEXT (Nobori Biolimus-Eluting Versus Xience/Promus Everolimus-Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age >=75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (>=4, n=682) was associated with higher 3-year incidence of thrombotic events than a score that was intermediate (2-3, n=1178) or low (0-1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P<0.0001). A high bleeding risk score (>=3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1-2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P<0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%). CONCLUSIONS: CREDO-Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk. PMID- 29789337 TI - Science and Culture: Artistic endeavors strive to save coral reefs. PMID- 29789340 TI - Death is no longer just in the hands of god or fate, but often a decision. PMID- 29789336 TI - Illness Identity: A Novel Predictor for Healthcare Use in Adults With Congenital Heart Disease. AB - BACKGROUND: To optimize healthcare use of adults with congenital heart disease, all important predictors of healthcare utilization should be identified. Clinical and psychological characteristics (eg, age and depression) have been found to be associated with healthcare use. However, the concept of illness identity, which assesses the degree to which congenital heart disease is integrated into one's identity, has not yet been investigated in association with healthcare use. Hence, the purpose of the study is to examine the predictive value of illness identity for healthcare use. METHODS AND RESULTS: In this ambispective analytical observational cohort study, 216 adults with congenital heart disease were included. The self-reported Illness Identity Questionnaire was used to assess illness identity states: engulfment, rejection, acceptance, and enrichment. After 1 year, self-reported healthcare use for congenital heart disease or other reasons over the past 6 months was assessed including hospitalizations; visits to general practitioner; visits to medical specialists; and emergency room visits. Binary logistic and negative binomial regression analyses were conducted, adjusting for age, sex, disease complexity, and depressive and anxious symptoms. The more profoundly the heart defect dominated one's identity (ie, engulfment), the more likely this person was to be hospitalized (odds ratio=3.76; 95% confidence interval=1.43-9.86), to visit a medical specialist (odds ratio=2.32; 95% confidence interval=1.35-4.00) or a general practitioner (odds ratio=1.78; 95% confidence interval=1.01-3.17), because of their heart defect. CONCLUSIONS: Illness identity, more specifically engulfment, has a unique predictive value for the occurrence of healthcare encounters. This association deserves further investigation, in which the directionality of effects and the contribution of illness identity in terms of preventing inappropriate healthcare use should be determined. PMID- 29789338 TI - Inner Workings: Zebrafish assay forges new approach to drug discovery. PMID- 29789343 TI - Even a $13 meal paid by pharma increases doctors' opioid prescribing, study finds. PMID- 29789341 TI - A novel CHCHD10 mutation implicates a Mia40-dependent mitochondrial import deficit in ALS. AB - CHCHD10 mutations are linked to amyotrophic lateral sclerosis, but their mode of action is unclear. In a 29-year-old patient with rapid disease progression, we discovered a novel mutation (Q108P) in a conserved residue within the coiled-coil helix-coiled-coil-helix (CHCH) domain. The aggressive clinical phenotype prompted us to probe its pathogenicity. Unlike the wild-type protein, mitochondrial import of CHCHD10 Q108P was blocked nearly completely resulting in diffuse cytoplasmic localization and reduced stability. Other CHCHD10 variants reported in patients showed impaired mitochondrial import (C122R) or clustering within mitochondria (especially G66V and E127K) often associated with reduced expression. Truncation experiments suggest mitochondrial import of CHCHD10 is mediated by the CHCH domain rather than the proposed N-terminal mitochondrial targeting signal. Knockdown of Mia40, which introduces disulfide bonds into CHCH domain proteins, blocked mitochondrial import of CHCHD10. Overexpression of Mia40 rescued mitochondrial import of CHCHD10 Q108P by enhancing disulfide-bond formation. Since reduction in CHCHD10 inhibits respiration, mutations in its CHCH domain may cause aggressive disease by impairing mitochondrial import. Our data suggest Mia40 upregulation as a potential therapeutic salvage pathway. PMID- 29789342 TI - CLK2 blockade modulates alternative splicing compromising MYC-driven breast tumors. PMID- 29789344 TI - PGC-1alpha as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer. AB - Colorectal cancer is a significant public health concern. As a multistage and multifactorial disease, environmental and genetic factors interact at each stage of the process, and an individual's lifestyle also plays a relevant role. We set out to review the scientific evidence to study the need to investigate the role of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC 1alpha) gene as a biomarker of the physical activity's (PA) effect on colorectal cancer. PA is a protective factor against colorectal cancer and usually increases the expression of PGC-1alpha This gene has pleiotropic roles and is the main regulator of mitochondrial functions. The development of colorectal cancer has been associated with mitochondrial dysfunction; in addition, alterations in this organelle are associated with colorectal cancer risk factors, such as obesity, decreased muscle mass, and the aging process. These are affected by PA acting, among other aspects, on insulin sensitivity and oxygen reactive species/redox balance. Therefore, this gene demands special attention in the understanding of its operation in the consensual protective effect of PA in colorectal cancer. A significant amount of indirect evidence points to PGC-1alpha as a potential biomarker in the PA-protective effect on colorectal cancer. The article focuses on the possible involvement of PGC-1alpha in the protective role that physical activity has on colorectal cancer. This is an important topic both in relation to advances in prevention of the development of this widespread disease and in its therapeutic treatment. We hope to generate an initial hypothesis for future studies associated with physical activity-related mechanisms that may be involved in the development or prevention of colorectal cancer. PGC-1alpha is highlighted because it is the main regulator of mitochondrial functions. This organelle, on one hand, is positively stimulated by physical activity; on the other hand, its dysfunction or reduction increases the probability of developing colorectal cancer. Therefore, we consider the compilation of existing information about the possible ways to understand the mechanisms of this gene to be highly relevant. This study is based on evidence of PGC-1alpha and physical activity, on PGC 1alpha and colorectal cancer, on colorectal cancer and physical activity/inactivity, and the absence of studies that have sought to relate all of these variables. Cancer Prev Res; 11(9); 523-34. (c)2018 AACR. PMID- 29789345 TI - The hidden costs of infertility treatment. PMID- 29789346 TI - Maternal polycystic ovarian syndrome and offspring growth: the Upstate KIDS Study. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common cause of female infertility and is associated with higher levels of circulating androgens. Exposure to higher levels of androgens in utero may be a risk factor for obesity among children of women with PCOS. METHODS: We examined whether maternal PCOS was associated with differences in offspring growth and obesity in the Upstate KIDS study, a prospective cohort study of infants born in New York State (excluding New York City) oversampled for fertility treatments and multiple births. Measurements of offspring length/height and weight were recorded at doctor's visits through 3 years of age. PCOS diagnosis was self-reported by mothers at baseline. We used linear mixed models with robust SEs to estimate differences in growth by maternal PCOS exposure. We used logistic regression to examine whether infants experienced rapid weight gain at 4, 9 and 12 months. Growth measures were reported by 4098 mothers for 4949 children (1745 twins). Of these, 435 mothers (10.6%) had a diagnosis of PCOS. RESULTS: Compared with children born to mothers without PCOS, children of mothers with PCOS did not have significant differences in weight (4.81 g, 95% CI -95.1 to 104.7), length/height (0.18 cm, 95% CI -0.16 to 0.52) and body mass index (-0.14 kg/m2, 95% CI -0.30 to 0.01) through 3 years of age. We also observed no association between maternal PCOS and offspring rapid weight gain. CONCLUSIONS: Overall, we found little evidence to suggest that maternal PCOS influences early childhood growth in this large, prospective cohort study. PMID- 29789347 TI - Scaling of avian bipedal locomotion reveals independent effects of body mass and leg posture on gait. AB - Birds provide an interesting opportunity to study the relationships between body size, limb morphology and bipedal locomotor function. Birds are ecologically diverse and span a large range of body size and limb proportions, yet all use their hindlimbs for bipedal terrestrial locomotion, for at least some part of their life history. Here, we review the scaling of avian striding bipedal gaits to explore how body mass and leg morphology influence walking and running. We collate literature data from 21 species, spanning a 2500* range in body mass from painted quail to ostriches. Using dynamic similarity theory to interpret scaling trends, we find evidence for independent effects of body mass, leg length and leg posture on gait. We find no evidence for scaling of duty factor with body size, suggesting that vertical forces scale with dynamic similarity. However, at dynamically similar speeds, large birds use relatively shorter stride lengths and higher stride frequencies compared with small birds. We also find that birds with long legs for their mass, such as the white stork and red-legged seriema, use longer strides and lower swing frequencies, consistent with the influence of high limb inertia on gait. We discuss the observed scaling of avian bipedal gait in relation to mechanical demands for force, work and power relative to muscle actuator capacity, muscle activation costs related to leg cycling frequency, and considerations of stability and agility. Many opportunities remain for future work to investigate how morphology influences gait dynamics among birds specialized for different habitats and locomotor behaviors. PMID- 29789348 TI - Gestational low-protein intake enhances whole-kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in rat adult male offspring. AB - Studies have shown that adult offspring of mothers fed a protein-restricted diet during pregnancy present a pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Additionally, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation and inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as a common factor. In the current study, protein and sodium urinary excretion rates were evaluated in rats, and immunohistochemistry and western blot techniques were used to characterize kidney structure changes in 16 week old male offspring of mothers fed a low-protein diet during pregnancy (LP group) compared with age-matched (NP) controls. We also verified the expression of miRNA, mRNA and protein markers of fibrosis and the EMT in whole kidney prepared from LP offspring. We found, surprisingly, that arterial hypertension and long-term hyperfiltration, manifest by proteinuria, were associated with increased renal miR-192 and miR-200 family expression in 16 week old LP relative to age-matched NP rats. Measurement of kidney fibrosis and EMT-related protein markers, by histochemistry and immunoblot techniques, showed a significant rise of TGF-beta1 and type-I collagen content in glomeruli and tubulointerstitial areas, accompanied by enhanced fibronectin and ZEB1 and decreased E-cadherin immunoreactivity in 16 week old LP offspring. The results were partially confirmed by increased gene (mRNA) expression of collagen 1alpha1, collagen 1alpha2 and ZEB1 in LP whole kidneys compared with those of age-matched NP offspring. In view of the presumed functional overload in the remaining nephrons, we suggest that hypertension and proteinuria development following maternal protein restriction may be a preponderant factor for EMT and structural kidney changes in LP offspring. However, our study was not wholly able to establish the precise role of miRNAs in LP kidney disorders. Thus, further studies will be required to assess the contribution of the miR family to renal injury in a gestational protein-restricted model of fetal programming. PMID- 29789349 TI - Passive water collection with the integument: mechanisms and their biomimetic potential. AB - Several mechanisms of water acquisition have evolved in animals living in arid habitats to cope with limited water supply. They enable access to water sources such as rain, dew, thermally facilitated condensation on the skin, fog, or moisture from a damp substrate. This Review describes how a significant number of animals - in excess of 39 species from 24 genera - have acquired the ability to passively collect water with their integument. This ability results from chemical and structural properties of the integument, which, in each species, facilitate one or more of six basic mechanisms: increased surface wettability, increased spreading area, transport of water over relatively large distances, accumulation and storage of collected water, condensation, and utilization of gravity. Details are described for each basic mechanism. The potential for bio-inspired improvement of technical applications has been demonstrated in many cases, in particular for several wetting phenomena, fog collection and passive, directional transport of liquids. Also considered here are potential applications in the fields of water supply, lubrication, heat exchangers, microfluidics and hygiene products. These present opportunities for innovations, not only in product functionality, but also for fabrication processes, where resources and environmental impact can be reduced. PMID- 29789350 TI - Regulatory T Cells and Kidney Transplantation. AB - The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor alpha chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off target, nonspecific, immunosuppressive effects related specially to cancer. PMID- 29789351 TI - Development and validation of two clinical prediction models to inform clinical decision-making for lumbar spinal fusion surgery for degenerative disorders and rehabilitation following surgery: protocol for a prospective observational study. AB - INTRODUCTION: Potential predictors of poor outcome will be measured at baseline: (1) preoperatively to develop a clinical prediction model to predict which patients are likely to have favourable outcome following lumbar spinal fusion surgery (LSFS) and (2) postoperatively to predict which patients are likely to have favourable long-term outcomes (to inform rehabilitation). METHODS AND ANALYSIS: Prospective observational study with a defined episode inception of the point of surgery. Electronic data will be collected through the British Spine Registry and will include patient-reported outcome measures (eg, Fear-Avoidance Beliefs Questionnaire) and data items (eg, smoking status). Consecutive patients (>=18 years) undergoing LSFS for back and/or leg pain of degenerative cause will be recruited. EXCLUSION CRITERIA: LSFS for spinal fracture, inflammatory disease, malignancy, infection, deformity and revision surgery. 1000 participants will be recruited (n=600 prediction model development, n=400 internal validation derived model; planning 10 events per candidate prognostic factor). The outcome being predicted is an individual's absolute risk of poor outcome (disability and pain) at 6 weeks (objective 1) and 12 months postsurgery (objective 2). Disability and pain will be measured using the Oswestry Disability Index (ODI), and severity of pain in the previous week with a Numerical Rating Scale (NRS 0-10), respectively. Good outcome is defined as a change of 1.7 on the NRS for pain, and a change of 14.3 on the ODI. Both linear and logistic (to dichotomise outcome into low and high risk) multivariable regression models will be fitted and mean differences or ORs for each candidate predictive factor reported. Internal validation of the derived model will use a further set of British Spine Registry data. External validation will be geographical using two spinal registries in The Netherlands and Switzerland. ETHICS AND DISSEMINATION: Ethical approval (University of Birmingham ERN_17-0446A). Dissemination through peer-reviewed journals and conferences. PMID- 29789354 TI - UK patients lose legal claim that DePuy metal-on-metal hip implant was "defective". PMID- 29789353 TI - The Power of Social Media in Medicine and Medical Education: Opportunities, Risks, and Rewards. PMID- 29789352 TI - Reporting quality of randomised controlled trial abstracts on age-related macular degeneration health care: a cross-sectional quantification of the adherence to CONSORT abstract reporting recommendations. AB - OBJECTIVE: To assess the reporting quality of randomised controlled trial (RCT) abstracts on age-related macular degeneration (AMD) healthcare, to evaluate the adherence to the Consolidated Standards of Reporting Trials (CONSORT) statement's recommendations on minimum abstract information and to identify journal characteristics associated with abstract reporting quality. DESIGN: Cross sectional evaluation of RCT abstracts on AMD healthcare. METHODS: A PubMed search was implemented to identify RCT abstracts on AMD healthcare published in the English language between January 2004 and December 2013. Data extraction was performed by two parallel readers independently by means of a documentation format in accordance with the 16 items of the CONSORT checklist for abstracts. The total number of criteria fulfilled by an abstract was derived as primary endpoint of the investigation; incidence rate ratios (IRRs) with unadjusted 95% CI were estimated by means of multiple Poisson regression to identify journal and article characteristics (publication year, multicentre design, structured abstract recommendations, effective sample size, effective abstract word counts and journal impact factor) possibly associated with the total number of fulfilled items. STUDY CHARACTERISTICS: 136 of 673 identified abstracts (published in 36 different journals) fulfilled all eligibility criteria. RESULTS: The median number of fulfilled items was 7 (95% CI 7 to 8). No abstract reported all 16 recommended items; the maximum total number was 14, the minimum 3 of 16 items. Multivariate analysis only demonstrated the abstracts' word counts as being significantly associated with a better reporting of abstracts (Poisson regression based IRR 1.002, 95% CI 1.001 to 1.003). CONCLUSIONS: Reporting quality of RCT abstracts on AMD investigations showed a considerable potential for improvement to meet the CONSORT abstract reporting recommendations. Furthermore, word counts of abstracts were identified as significantly associated with the overall abstract reporting quality. PMID- 29789355 TI - HDL functionality and cardiovascular outcome among nondialysis chronic kidney disease patients. AB - CVD remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD profoundly affects HDL composition and functionality, but whether abnormal HDL independently contributes to cardiovascular events in CKD patients remains elusive. In the present study, we assessed whether compositional and functional properties of HDL predict cardiovascular outcome among 526 nondialysis CKD patients who participate in the CARE FOR HOMe study. We measured HDL cholesterol, the content of HDL-associated proinflammatory serum amyloid A (SAA), and activities of the HDL enzymes paraoxonase and lipoprotein associated phospholipase A2 (Lp-PLA2). In addition, we assessed the antioxidative activity of apoB-depleted serum. During a mean follow-up of 5.1 +/- 2.1 years, 153 patients reached the predefined primary endpoint, a composite of atherosclerotic cardiovascular events including cardiovascular mortality and death of any cause. In univariate Cox regression analyses, lower HDL-cholesterol levels, higher HDL-associated SAA content, and lower paraoxonase activity predicted cardiovascular outcome, while Lp-PLA2 activity and antioxidative capacity did not. HDL-cholesterol and HDL-paraoxonase activity lost their association with cardiovascular outcome after adjustment for traditional cardiovascular and renal risk factors, while SAA lost its association after further adjustment for C-reactive protein. In conclusion, our data suggest that neither HDL quantity nor HDL composition or function independently predict cardiovascular outcome among nondialysis CKD patients. PMID- 29789356 TI - Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL. AB - Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 * 109/L or >=10 * 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40. PMID- 29789358 TI - Divide and Conquer: High-Throughput Screening of Chlamydomonas Cell Cycle Mutants. PMID- 29789357 TI - Reactivation of gamma-globin in adult beta-YAC mice after ex vivo and in vivo hematopoietic stem cell genome editing. AB - Disorders involving beta-globin gene mutations, primarily beta-thalassemia and sickle cell disease, represent a major target for hematopoietic stem/progenitor cell (HSPC) gene therapy. This includes CRISPR/Cas9-mediated genome editing approaches in adult CD34+ cells aimed toward the reactivation of fetal gamma globin expression in red blood cells. Because models involving erythroid differentiation of CD34+ cells have limitations in assessing gamma-globin reactivation, we focused on human beta-globin locus-transgenic (beta-YAC) mice. We used a helper-dependent human CD46-targeting adenovirus vector expressing CRISPR/Cas9 (HDAd-HBG-CRISPR) to disrupt a repressor binding region within the gamma-globin promoter. We transduced HSPCs from beta-YAC/human CD46-transgenic mice ex vivo and subsequently transplanted them into irradiated recipients. Furthermore, we used an in vivo HSPC transduction approach that involves HSPC mobilization and the intravenous injection of HDAd-HBG-CRISPR into beta-YAC/CD46 transgenic mice. In both models, we demonstrated efficient target site disruption, resulting in a pronounced switch from human beta- to gamma-globin expression in red blood cells of adult mice that was maintained after secondary transplantation of HSPCs. In long-term follow-up studies, we did not detect hematological abnormalities, indicating that HBG promoter editing does not negatively affect hematopoiesis. This is the first study that shows successful in vivo HSPC genome editing by CRISPR/Cas9. PMID- 29789359 TI - Conserved Responses in a War of Small Molecules between a Plant-Pathogenic Bacterium and Fungi. AB - Small-molecule signaling is one major mode of communication within the polymicrobial consortium of soil and rhizosphere. While microbial secondary metabolite (SM) production and responses of individual species have been studied extensively, little is known about potentially conserved roles of SM signals in multilayered symbiotic or antagonistic relationships. Here, we characterize the SM-mediated interaction between the plant-pathogenic bacterium Ralstonia solanacearum and the two plant-pathogenic fungi Fusarium fujikuroi and Botrytis cinerea We show that cellular differentiation and SM biosynthesis in F. fujikuroi are induced by the bacterially produced lipopeptide ralsolamycin (synonym ralstonin A). In particular, fungal bikaverin production is induced and preferentially accumulates in fungal survival spores (chlamydospores) only when exposed to supernatants of ralsolamycin-producing strains of R. solanacearum Although inactivation of bikaverin biosynthesis moderately increases chlamydospore invasion by R. solanacearum, we show that other metabolites such as beauvericin are also induced by ralsolamycin and contribute to suppression of R. solanacearum growth in vitro Based on our findings that bikaverin antagonizes R. solanacearum and that ralsolamycin induces bikaverin biosynthesis in F. fujikuroi, we asked whether other bikaverin-producing fungi show similar responses to ralsolamycin. Examining a strain of B. cinerea that horizontally acquired the bikaverin gene cluster from Fusarium, we found that ralsolamycin induced bikaverin biosynthesis in this fungus. Our results suggest that conservation of microbial SM responses across distantly related fungi may arise from horizontal transfer of protective gene clusters that are activated by conserved regulatory cues, e.g., a bacterial lipopeptide, providing consistent fitness advantages in dynamic polymicrobial networks.IMPORTANCE Bacteria and fungi are ubiquitous neighbors in many environments, including the rhizosphere. Many of these organisms are notorious as economically devastating plant pathogens, but little is known about how they communicate chemically with each other. Here, we uncover a conserved antagonistic communication between the widespread bacterial wilt pathogen Ralstonia solanacearum and plant-pathogenic fungi from disparate genera, Fusarium and Botrytis Exposure of Fusarium fujikuroi to the bacterial lipopeptide ralsolamycin resulted in production of the antibacterial metabolite bikaverin specifically in fungal tissues invaded by Ralstonia Remarkably, ralsolamycin induction of bikaverin was conserved in a Botrytis cinerea isolate carrying a horizontally transferred bikaverin gene cluster. These results indicate that horizontally transferred gene clusters may carry regulatory prompts that contribute to conserved fitness functions in polymicrobial environments. PMID- 29789361 TI - Breaching Pathogeographic Barriers by the Bat White-Nose Fungus. AB - Bat white-nose syndrome has become associated with unparalleled mortality in bat species across the United States since 2006. In a recent article, Drees and colleagues (mBio 8:e01941-17, 2017, https://doi.org/10.1128/mBio.01941-17) utilized both whole-genome sequencing and microsatellite data to explore the origin and spread of the causative agent of bat white-nose syndrome, Pseudogymnoascus destructans The research by Drees et al. supports the hypothesis that P. destructans was introduced into North America from Europe, with molecular dating suggesting a divergence from European isolates approximately 100 years ago. The approaches described in this study are an important contribution toward pinpointing the origins of this infection and underscore the need for more rigorous international biosecurity in order to stem the tide of emerging fungal pathogens. PMID- 29789362 TI - Reply to Forni et al., "Multiple Selected Changes May Modulate the Molecular Interaction between Laverania RH5 and Primate Basigin". PMID- 29789360 TI - Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles. AB - Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to "recoviruses." Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens.IMPORTANCE Caliciviruses are rapidly evolving viruses that cause pandemic outbreaks associated with significant morbidity and mortality globally. The animal reservoirs for human caliciviruses are unknown; bats represent critical reservoir species for several emerging and zoonotic diseases. Recent reports have identified several bat caliciviruses but have not characterized biological functions associated with disease risk, including their potential emergence in other mammalian populations. In this report, we identified a novel bat calicivirus that is most closely related to nonhuman primate caliciviruses. Using this new bat calicivirus and a second norovirus-like bat calicivirus capsid gene sequence, we generated virus-like particles that have host carbohydrate ligand binding patterns similar to those of human and animal noroviruses and that share antigens with human noroviruses. The similarities to human noroviruses with respect to binding patterns and antigenic epitopes illustrate the potential for bat caliciviruses to emerge in other species and the importance of pathogen surveillance in wild-animal populations. PMID- 29789363 TI - Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis. AB - Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice.IMPORTANCE Collectively, these results demonstrate key roles for the ion channel and PBM domains in optimal virus replication and pathogenesis and suggest that the viral viroporins and PBMs are suitable targets for antiviral therapy and for mutation in attenuated SARS-CoV vaccines. PMID- 29789365 TI - Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial. AB - Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp.IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula. PMID- 29789364 TI - Bacterial Quorum Sensing and Microbial Community Interactions. AB - Many bacteria use a cell-cell communication system called quorum sensing to coordinate population density-dependent changes in behavior. Quorum sensing involves production of and response to diffusible or secreted signals, which can vary substantially across different types of bacteria. In many species, quorum sensing modulates virulence functions and is important for pathogenesis. Over the past half-century, there has been a significant accumulation of knowledge of the molecular mechanisms, signal structures, gene regulons, and behavioral responses associated with quorum-sensing systems in diverse bacteria. More recent studies have focused on understanding quorum sensing in the context of bacterial sociality. Studies of the role of quorum sensing in cooperative and competitive microbial interactions have revealed how quorum sensing coordinates interactions both within a species and between species. Such studies of quorum sensing as a social behavior have relied on the development of "synthetic ecological" models that use nonclonal bacterial populations. In this review, we discuss some of these models and recent advances in understanding how microbes might interact with one another using quorum sensing. The knowledge gained from these lines of investigation has the potential to guide studies of microbial sociality in natural settings and the design of new medicines and therapies to treat bacterial infections. PMID- 29789367 TI - Multiple Selected Changes May Modulate the Molecular Interaction between Laverania RH5 and Primate Basigin. PMID- 29789368 TI - The Case for an Expanded Concept of Trained Immunity. AB - Trained immunity was originally proposed as a program of innate immunity memory by innate immunity cells of hematopoietic origin such as the monocytes/macrophages and the NK cells. Here I discuss some old and new data justifying this program and some specific, still unanswered, questions it raises regarding the model fungus Candida albicans and the chronic, inflammatory vulvovaginal disease it causes. Building upon this well-established program, the recent reports that epithelial cells of mammals can also acquire memory from previous stimulations, and the apparent intrinsic ability of many living cells from bacteria to mammals to learn from experience, I suggest an expansion of the concept of trained immunity to include all cells of different lineages with the potential of memorizing previous microbial encounters. This expansion would better fit the complexity of innate immunity and the role it plays in infectious and inflammatory diseases. PMID- 29789366 TI - Loss of Upc2p-Inducible ERG3 Transcription Is Sufficient To Confer Niche-Specific Azole Resistance without Compromising Candida albicans Pathogenicity. AB - Inactivation of sterol Delta5,6-desaturase (Erg3p) in the prevalent fungal pathogen Candida albicans is one of several mechanisms that can confer resistance to the azole antifungal drugs. However, loss of Erg3p activity is also associated with deficiencies in stress tolerance, invasive hyphal growth, and attenuated virulence in a mouse model of disseminated infection. This may explain why relatively few erg3-deficient strains have been reported among azole-resistant clinical isolates. In this study, we examined the consequences of Erg3p inactivation upon C. albicans pathogenicity and azole susceptibility in mouse models of mucosal and disseminated infection. While a C. albicanserg3Delta/Delta mutant was unable to cause lethality in the disseminated model, it induced pathology in a mouse model of vaginal infection. The erg3Delta/Delta mutant was also more resistant to fluconazole treatment than the wild type in both models of infection. Thus, complete loss of Erg3p activity confers azole resistance but also niche-specific virulence deficiencies. Serendipitously, we discovered that loss of azole-inducible ERG3 transcription (rather than complete inactivation) is sufficient to confer in vitro fluconazole resistance, without compromising C. albicans stress tolerance, hyphal growth, or pathogenicity in either mouse model. It is also sufficient to confer fluconazole resistance in the mouse vaginal model, but not in the disseminated model of infection, and thus confers niche specific azole resistance without compromising C. albicans pathogenicity at either site. Collectively, these results establish that modulating Erg3p expression or activity can have niche-specific consequences on both C. albicans pathogenicity and azole resistance.IMPORTANCE While conferring resistance to the azole antifungals in vitro, loss of sterol Delta5,6-desaturase (Erg3p) activity has also been shown to reduce C. albicans pathogenicity. Accordingly, it has been presumed that this mechanism may not be significant in the clinical setting. The results presented here challenge this assumption, revealing a more complex relationship between Erg3p activity, azole resistance, C. albicans pathogenicity, and the specific site of infection. Most importantly, we have shown that even modest changes in ERG3 transcription are sufficient to confer azole resistance without compromising C. albicans fitness or pathogenicity. Given that previous efforts to assess the importance of ERG3 as a determinant of clinical azole resistance have focused almost exclusively on detecting null mutants, its role may have been grossly underestimated. On the basis of our results, a more thorough investigation of the contribution of the ERG3 gene to azole resistance in the clinical setting is warranted. PMID- 29789369 TI - Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication. AB - Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia wStri, isolated from Laodelphax striatellus, was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that wStri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. wStri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by wStri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into wStri-infected cells. This was partially rescued by the addition of a cholesterol lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia-infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in wStri infected cells. This study's findings increase the potential for application of wStri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection.IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia wStri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia wStri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy. PMID- 29789370 TI - A Single-Domain Response Regulator Functions as an Integrating Hub To Coordinate General Stress Response and Development in Alphaproteobacteria. AB - The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria.IMPORTANCE Two-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross talk, TCSs are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alphaproteobacterial general stress response. Here, we show that in the model organism Caulobacter crescentus an atypical FATGUY-type single domain response regulator, MrrA, is highly promiscuous in accepting and transferring phosphoryl groups from and to multiple up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alphaproteobacteria as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors. PMID- 29789372 TI - Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline. PMID- 29789371 TI - Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses. AB - BACKGROUND: Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. OBJECTIVE: To identify rare, causal CNV in patients with RE. METHODS: We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. RESULTS: We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies (KCTD7, ARHGEF15, CACNA2D1, GRIN2A and ARHGEF4), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. CONCLUSION: Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation. PMID- 29789373 TI - Voltage-Gated Calcium Influx Modifies Cholinergic Inhibition of Inner Hair Cells in the Immature Rat Cochlea. AB - Until postnatal day (P) 12, inner hair cells of the rat cochlea are invested with both afferent and efferent synaptic connections. With the onset of hearing at P12, the efferent synapses disappear, and afferent (ribbon) synapses operate with greater efficiency. This change coincides with increased expression of voltage gated potassium channels, the loss of calcium-dependent electrogenesis, and the onset of graded receptor potentials driven by sound. The transient efferent synapses include near-membrane postsynaptic cisterns thought to regulate calcium influx through the hair cell's alpha9-containing and alpha10-containing nicotinic acetylcholine receptors. This influx activates small-conductance Ca2+-activated K+ (SK) channels. Serial-section electron microscopy of inner hair cells from two 9-d-old (male) rat pups revealed many postsynaptic efferent cisterns and presynaptic afferent ribbons whose average minimal separation in five cells ranged from 1.1 to 1.7 MUm. Efferent synaptic function was studied in rat pups (age, 7-9 d) of either sex. The duration of these SK channel-mediated IPSCs was increased by enhanced calcium influx through L-type voltage-gated channels, combined with ryanodine-sensitive release from internal stores-presumably the near-membrane postsynaptic cistern. These data support the possibility that inner hair cell calcium electrogenesis modulates the efficacy of efferent inhibition during the maturation of inner hair cell synapses.SIGNIFICANCE STATEMENT Strict calcium buffering is essential for cellular function. This problem is especially acute for compact hair cells where increasing cytoplasmic calcium promotes the opposing functions of closely adjoining afferent and efferent synapses. The near membrane postsynaptic cistern at efferent synapses segregates synaptic calcium signals by acting as a dynamic calcium store. The hair cell serves as an informative model for synapses with postsynaptic cisterns (C synapses) found in central neurons. PMID- 29789374 TI - Identification and Characterization of a Novel Spontaneously Active Bursty GABAergic Interneuron in the Mouse Striatum. AB - The recent availability of different transgenic mouse lines coupled with other modern molecular techniques has led to the discovery of an unexpectedly large cellular diversity and synaptic specificity in striatal interneuronal circuitry. Prior research has described three spontaneously active interneuron types in mouse striatal slices: the cholinergic interneuron, the neuropeptide Y-low threshold spike interneuron, and the tyrosine hydroxylase interneurons (THINs). Using transgenic Htr3a-Cre mice, we now characterize a fourth population of spontaneously active striatal GABAergic interneurons termed spontaneously active bursty interneurons (SABIs) because of their unique burst-firing pattern in cell attached recordings. Although they bear some qualitative similarity in intrinsic electrophysiological properties to THINs in whole-cell recordings, detailed analysis revealed significant differences in many intrinsic properties and in their morphology. Furthermore, all previously identified striatal GABAergic interneurons have been shown to innervate striatal spiny projection neurons (SPNs), contributing to the suggestion that the principal function of striatal GABAergic interneurons is to provide feedforward inhibition to SPNs. Here, very surprisingly, paired recordings show that SABIs do not innervate SPNs significantly. Further, optogenetic inhibition of striatal Htr3a-Cre interneurons triggers barrages of IPSCs in SPNs. We hypothesize that these IPSCs result from disinhibition of a population of GABAergic interneurons with activity that is constitutively suppressed by the SABIs. We suggest that the SABIs represent the first example of a striatal interneuron-selective interneuron and, further, that their existence, along with previously defined interneuronal networks, may participate in the formation of SPN ensembles observed by others.SIGNIFICANCE STATEMENT Before ~2010, the main function of the three known subtypes of striatal GABAergic interneurons was assumed to mediate feedforward inhibition of the spiny neurons (SPNs). During the past decade, we and others have described several novel populations of striatal GABAergic interneurons and their synaptic connections and have shown that striatal interneurons and SPNs interact through extensive and highly cell-type-specific connections that form specialized networks. Here, we describe a novel population of striatal GABAergic interneuron and provide several lines of evidence suggesting that it represents the first interneuron-selective interneuron in striatum. Striatal interneurons and their synaptic connections are suggested to play an important role in the formation of ensembles of striatal SPNs interconnected by inhibitory axon collaterals. PMID- 29789375 TI - Neurotrophin Responsiveness of Sympathetic Neurons Is Regulated by Rapid Mobilization of the p75 Receptor to the Cell Surface through TrkA Activation of Arf6. AB - The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is upregulated, resulting in formation of TrkA-p75 complexes, which are high-affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 guanine nucleotide exchange factors. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth, whereas the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system.SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface availability may provide insight into how and why neurodegenerative processes manifest and reveal new therapeutic targets. Results from this study indicate a novel mechanism by which p75NTR can be rapidly shuttled to the cell surface from existing intracellular pools and explores a unique pathway by which NGF regulates the sympathetic innervation of target tissues, which has profound consequences for the function of these organs. PMID- 29789377 TI - Polyamine Modulation of Anticonvulsant Drug Response: A Potential Mechanism Contributing to Pharmacoresistance in Chronic Epilepsy. AB - Despite the development of numerous novel anticonvulsant drugs, ~30% of epilepsy patients remain refractory to antiepileptic drugs (AEDs). Many established and novel AEDs reduce hyperexcitability via voltage- and use-dependent inhibition of voltage-gated Na+ channels. For the widely used anticonvulsant carbamazepine (CBZ), use-dependent block of Na+ channels is significantly reduced both in experimental and human epilepsy. However, the molecular underpinnings of this potential cellular mechanism for pharmacoresistance have remained enigmatic.Here, we describe the mechanism that leads to the emergence of CBZ-resistant Na+ channels. We focused on the endogenous polyamine system, which powerfully modulates Na+ channels in a use-dependent manner. We had shown previously that the intracellular polyamine spermine is reduced in chronic epilepsy, resulting in increased persistent Na+ currents. Because spermine and CBZ both bind use dependently in spatial proximity within the Na+ channel pore, we hypothesized that spermine loss might also be related to diminished CBZ response. Using the pilocarpine model of refractory epilepsy in male rats and whole-cell patch-clamp recordings, we first replicated the reduction of use-dependent block by CBZ in chronically epileptic animals. We then substituted intracellular spermine via the patch pipette in different concentrations. Under these conditions, we found that exogenous spermine significantly rescues use-dependent block of Na+ channels by CBZ. These findings indicate that an unexpected modulatory mechanism, depletion of intracellular polyamines, leads both to increased persistent Na+ currents and to diminished CBZ sensitivity of Na+ channels. These findings could lead to novel strategies for overcoming pharmacoresistant epilepsy that target the polyamine system.SIGNIFICANCE STATEMENT Pharmacoresistant epilepsy affects ~18 million people worldwide, and intense efforts have therefore been undertaken to uncover the underlying molecular and cellular mechanisms. One of the key known candidate mechanisms of pharmacoresistance has been a loss of use-dependent Na+ channel block by the anticonvulsant carbamazepine (CBZ), both in human and experimental epilepsies. Despite intense scrutiny, the molecular mechanisms underlying this phenomenon have not been elucidated. We now show that a loss of intracellular spermine in chronic epilepsy is a major causative factor leading to the development of CBZ-resistant Na+ currents. This finding can be exploited both for the screening of anticonvulsants in expression systems, and for novel strategies to overcome pharmacoresistance that target the polyamine system. PMID- 29789376 TI - Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses. AB - Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin-expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively. An ex vivo preparation of the colon was used for single-fiber analysis of colon sensory afferents of the pelvic nerve. Afferents were characterized using previously described criteria as mucosal, muscular, muscular-mucosal, or serosal and then tested for blue light induced activation. Light activation of colon epithelial cells produced robust firing of action potentials, similar to that elicited by physiologic stimulation (e.g., circumferential stretch), in 50.5% of colon afferents of mice homozygous for ChR2 expression. Light-induced activity could be reduced or abolished in most fibers using a cocktail of purinergic receptor blockers suggesting ATP release by the epithelium contributed to generation of sensory neuron action potentials. Using electromyographic recording of visceromotor responses we found that light stimulation of the colon epithelium evoked behavioral responses in Vil-ChR2 mice that was similar to that seen with balloon distension of the colon. These ex vivo and in vivo data indicate that light stimulation of colon epithelial cells alone, without added mechanical or chemical stimuli, can directly activate colon afferents and elicit behavioral responses.SIGNIFICANCE STATEMENT Abdominal pain that accompanies inflammatory diseases of the bowel is particularly vexing because it can occur without obvious changes in the structure or inflammatory condition of the colon. Pain reflects abnormal sensory neuron activity that may be controlled in part by release of substances from lining epithelial cells. In support of this mechanism we determined that blue-light stimulation of channelrhodopsin-expressing colon epithelial cells could evoke action potential firing in sensory neurons and produce changes in measures of behavioral sensitivity. Thus, activity of colon epithelial cells alone, without added mechanical or chemical stimuli, is sufficient to activate pain-sensing neurons. PMID- 29789380 TI - Metaplasticity in the Visual Cortex: Crosstalk Between Visual Experience and Reactive Oxygen Species. AB - Metaplasticity is the regulation of synaptic plasticity based on the history of previous synaptic activation. This concept was formulated after observing that synaptic changes in the visual cortex are not fixed, but dynamic and dependent on the history of visual information flux. In visual cortical neurons, sustained synaptic stimulation activate the enzymatic complex NOX2, resulting in the generation of reactive oxygen species (ROS). NOX2 is the main molecular structure responsible for translating neural activity into redox modulation of intracellular signaling pathways involved in plastic changes. Here, we studied the interaction between NOX2 and visual experience as metaplastic factors regulating synaptic plasticity at the supergranular layers of the mouse visual cortex. We found that genetic inhibition of NOX2 reverses the polarizing effects of dark rearing from LTP to LTD. In addition, we demonstrate that this process relies on changes in the NMDA receptor functioning. Altogether, this work indicates a role of ROS in the activity-dependent regulation of cortical synaptic plasticity.SIGNIFICANCE STATEMENT Synaptic plasticity in the visual cortex is modulated by the history of sensory experience and this modulation has been defined as metaplasticity. Dark rearing facilitates synaptic potentiation as a mechanism optimizing the range of synaptic modification. This process requires the production of reactive oxygen species mediated by the enzymatic complex NOX2. If the activity of NOX2 is inhibited, then visual deprivation results in synaptic depression. These findings increase our knowledge about metaplasticity and help in our understanding of how neural activity modulates cellular mechanisms of synaptic change. PMID- 29789378 TI - Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production. AB - Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech. PMID- 29789379 TI - Correlated Gene Expression and Anatomical Communication Support Synchronized Brain Activity in the Mouse Functional Connectome. AB - Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting-state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI.SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still primarily unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting-state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be used to streamline preclinical animal studies of disease. PMID- 29789381 TI - WT1-Expressing Interneurons Regulate Left-Right Alternation during Mammalian Locomotor Activity. AB - The basic pattern of activity underlying stepping in mammals is generated by a neural network located in the caudal spinal cord. Within this network, the specific circuitry coordinating left-right alternation has been shown to involve several groups of molecularly defined interneurons. Here we characterize a population of spinal neurons that express the Wilms' tumor 1 (WT1) gene and investigate their role during locomotor activity in mice of both sexes. We demonstrate that WT1-expressing cells are located in the ventromedial region of the spinal cord of mice and are also present in the human spinal cord. In the mouse, these cells are inhibitory, project axons to the contralateral spinal cord, terminate in close proximity to other commissural interneuron subtypes, and are essential for appropriate left-right alternation during locomotion. In addition to identifying WT1-expressing interneurons as a key component of the locomotor circuitry, this study provides insight into the manner in which several populations of molecularly defined interneurons are interconnected to generate coordinated motor activity on either side of the body during stepping.SIGNIFICANCE STATEMENT In this study, we characterize WT1-expressing spinal interneurons in mice and demonstrate that they are commissurally projecting and inhibitory. Silencing of this neuronal population during a locomotor task results in a complete breakdown of left-right alternation, whereas flexor-extensor alternation was not significantly affected. Axons of WT1 neurons are shown to terminate nearby commissural interneurons, which coordinate motoneuron activity during locomotion, and presumably regulate their activity. Finally, the WT1 gene is shown to be present in the spinal cord of humans, raising the possibility of functional homology between these species. This study not only identifies a key component of the locomotor circuitry but also begins to unravel the connectivity among the growing number of molecularly defined interneurons that comprise this neural network. PMID- 29789382 TI - Robustness and universality of surface states in Dirac materials. AB - Ballistically propagating topologically protected states harbor exotic transport phenomena of wide interest. Here we describe a nontopological mechanism that produces such states at the surfaces of generic Dirac materials, giving rise to propagating surface modes with energies near the bulk band crossing. The robustness of surface states originates from the unique properties of Dirac-Bloch wavefunctions which exhibit strong coupling to generic boundaries. Surface states, described by Jackiw-Rebbi-type bound states, feature a number of interesting properties. Mode dispersion is gate tunable, exhibiting a wide variety of different regimes, including nondispersing flat bands and linear crossings within the bulk bandgap. The ballistic wavelike character of these states resembles the properties of topologically protected states; however, it requires neither topological restrictions nor additional crystal symmetries. The Dirac surface states are weakly sensitive to surface disorder and can dominate edge transport at the energies near the Dirac point. PMID- 29789383 TI - T7 phage factor required for managing RpoS in Escherichia coli. AB - T7 development in Escherichia coli requires the inhibition of the housekeeping form of the bacterial RNA polymerase (RNAP), Esigma70, by two T7 proteins: Gp2 and Gp5.7. Although the biological role of Gp2 is well understood, that of Gp5.7 remains to be fully deciphered. Here, we present results from functional and structural analyses to reveal that Gp5.7 primarily serves to inhibit EsigmaS, the predominant form of the RNAP in the stationary phase of growth, which accumulates in exponentially growing E. coli as a consequence of the buildup of guanosine pentaphosphate [(p)ppGpp] during T7 development. We further demonstrate a requirement of Gp5.7 for T7 development in E. coli cells in the stationary phase of growth. Our finding represents a paradigm for how some lytic phages have evolved distinct mechanisms to inhibit the bacterial transcription machinery to facilitate phage development in bacteria in the exponential and stationary phases of growth. PMID- 29789385 TI - Transparency on scientific instruments. PMID- 29789384 TI - Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication. AB - Circadian period and phase of cultivated tomato (Solanum lycopersicum) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1, the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock. PMID- 29789387 TI - Mitochondrial adaptation in obesity is a ClpPicated business. PMID- 29789386 TI - Antagonistic interactions between two MAP kinase cascades in plant development and immune signaling. AB - Mitogen-activated protein kinase (MAPK) signaling plays important roles in diverse biological processes. In Arabidopsis, MPK3/MPK6, MKK4/MKK5, and the MAPKKK YODA (YDA) form a MAPK pathway that negatively regulates stomatal development. Brassinosteroid (BR) stimulates this pathway to inhibit stomata production. In addition, MPK3/MPK6 and MKK4/MKK5 also serve as critical signaling components in plant immunity. Here, we report that MAPKKK3/MAPKKK5 form a kinase cascade with MKK4/MKK5 and MPK3/MPK6 to transduce defense signals downstream of multiple plant receptor kinases. Loss of MAPKKK3/MAPKKK5 leads to reduced activation of MPK3/MPK6 in response to different pathogen-associated molecular patterns (PAMPs) and increased susceptibility to pathogens. Surprisingly, developmental defects caused by silencing of YDA are suppressed in the mapkkk3 mapkkk5 double mutant. On the other hand, loss of YDA or blocking BR signaling leads to increased PAMP-induced activation of MPK3/MPK6. These results reveal antagonistic interactions between a developmental MAPK pathway and an immune signaling MAPK pathway. PMID- 29789388 TI - Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression. AB - A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes attributed to tonic commensal stimulation of this site. In contrast, almost all other tissues contain locally maintained macrophage populations, which coexist with monocyte-replenished cells at homeostasis. In this study, we identified three transcriptionally distinct mouse gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4+CD4+ gut macrophages were found to be locally maintained, while Tim-4-CD4+ macrophages had a slow turnover from blood monocytes; indeed, Tim-4-CD4- macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult mouse gut rapidly turn over from monocytes in a microbiome-dependent manner; instead, these findings supplant it with a model of ontogenetic diversity where locally maintained subsets coexist with rapidly replaced monocyte-derived populations. PMID- 29789389 TI - LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages. AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages. Moreover, inhibition of LRRK2 kinase activity in mouse and human macrophages enhanced Mycobacterium tuberculosis phagosome maturation and mycobacterial control independently of autophagy. In vivo, LRRK2 deficiency in mice resulted in a significant decrease in M. tuberculosis burdens early during the infection. Collectively, our findings provide a molecular mechanism explaining genetic evidence linking LRRK2 to mycobacterial diseases and establish an LRRK2-dependent cellular pathway that controls M. tuberculosis replication by regulating phagosome maturation. PMID- 29789391 TI - MST2 kinase suppresses rDNA transcription in response to DNA damage by phosphorylating nucleolar histone H2B. AB - The heavily transcribed rDNA repeats that give rise to the ribosomal RNA are clustered in a unique chromatin structure, the nucleolus. Due to its highly repetitive nature and transcriptional activity, the nucleolus is considered a hotspot of genomic instability. Breaks in rDNA induce a transient transcriptional shut down to conserve energy and promote rDNA repair; however, how nucleolar chromatin is modified and impacts on rDNA repair is unknown. Here, we uncover that phosphorylation of serine 14 on histone H2B marks transcriptionally inactive nucleolar chromatin in response to DNA damage. We identified that the MST2 kinase localises at the nucleoli and targets phosphorylation of H2BS14p in an ATM dependent manner. We show that establishment of H2BS14p is necessary for damage induced rDNA transcriptional shut down and maintenance of genomic integrity. Ablation of MST2 kinase, or upstream activators, results in defective establishment of nucleolar H2BS14p, perturbed DNA damage repair, sensitisation to rDNA damage and increased cell lethality. We highlight the impact of chromatin regulation in the rDNA damage response and targeting of the nucleolus as an emerging cancer therapeutic approach. PMID- 29789390 TI - The assembly of lipid droplets and their roles in challenged cells. AB - Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change. Cellular stresses such as starvation and invasion are internal insults that evoke changes in droplet metabolism and dynamics. This review will first outline lipid droplet assembly and then discuss how droplets respond to stress and in particular nutrient starvation. Finally, the role of droplets in viral and microbial invasion will be presented, where an unresolved issue is whether changes in droplet abundance promote the invader, defend the host, to try to do both. The challenges of stress and infection are often accompanied by changes in physical contacts between droplets and other organelles. How these changes may result in improving cellular physiology, an ongoing focus in the field, is discussed. PMID- 29789392 TI - FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. AB - To exploit vulnerabilities of tumors, it is urgent to identify associated defects in genome maintenance. One unsolved problem is the mechanism of regulation of DNA double-strand break repair by REV7 in complex with 53BP1 and RIF1, and its influence on repair pathway choice between homologous recombination and non homologous end-joining. We searched for REV7-associated factors in human cells and found FAM35A, a previously unstudied protein with an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single stranded DNA-binding protein RPA, as novel interactor of REV7/RIF1/53BP1. FAM35A re-localized in damaged cell nuclei, and its knockdown caused sensitivity to DNA damaging agents. In a BRCA1-mutant cell line, however, depletion of FAM35A increased resistance to camptothecin, suggesting that FAM35A participates in processing of DNA ends to allow more efficient DNA repair. We found FAM35A absent in one widely used BRCA1-mutant cancer cell line (HCC1937) with anomalous resistance to PARP inhibitors. A survey of FAM35A alterations revealed that the gene is altered at the highest frequency in prostate cancers (up to 13%) and significantly less expressed in metastatic cases, revealing promise for FAM35A as a therapeutically relevant cancer marker. PMID- 29789394 TI - Joining a Multicenter Clinical Trial. PMID- 29789393 TI - Long-Term Outcomes in Patients Aged <=70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis. AB - BACKGROUND AND PURPOSE: We aimed to determine whether subjects aged <=70 years who were treated with intravenous glyburide (RP-1127; BIIB093; glibenclamide) would have better long-term outcomes than those who received placebo. METHODS: GAMES-RP (Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals) was a prospective, double-blind, randomized, placebo-controlled phase 2 clinical trial. Eighty-six participants, aged 18 to 80 years, who presented to 18 centers with large hemispheric infarction (baseline diffusion weighted imaging volumes, 82-300 cm3) randomized within 10 hours of symptom onset were enrolled. In the current exploratory analysis, we included participants aged <=70 years treated with intravenous glyburide (n=35) or placebo (n=30) who met per-protocol criteria. Intravenous glyburide or placebo was administered in a 1:1 ratio. We analyzed 90-day and 12-month mortality, functional outcome (modified Rankin Scale, Barthel Index), and quality of life (EuroQol group 5-dimension). Additional outcomes assessed included blood-brain barrier injury (MMP-9 [matrix metalloproteinase 9]) and cerebral edema (brain midline shift). RESULTS: Participants <=70 years of age treated with intravenous glyburide had lower mortality at all time points (log-rank for survival hazards ratio, 0.34; P=0.04). After adjustment for age, the difference in functional outcome (modified Rankin Scale) demonstrated a trend toward benefit for intravenous glyburide-treated subjects at 90 days (odds ratio, 2.31; P=0.07). Repeated measures analysis at 90 days, 6 months, and 12 months using generalized estimating equations showed a significant treatment effect of intravenous glyburide on the Barthel Index (P=0.03) and EuroQol group 5-dimension (P=0.05). Participants treated with intravenous glyburide had lower plasma levels of MMP-9 (189 versus 376 ng/mL; P<0.001) and decreased midline shift (4.7 versus 9 mm; P<0.001) compared with participants who received placebo. CONCLUSIONS: In this exploratory analysis, participants <=70 years of age with large hemispheric infarction have improved survival after acute therapy with intravenous glyburide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182. PMID- 29789395 TI - Blood Pressure-Attained Analysis of ATACH 2 Trial. AB - BACKGROUND AND PURPOSE: We compared the rates of death or disability, defined by modified Rankin Scale score of 4 to 6, at 3 months in patients with intracerebral hemorrhage according to post-treatment systolic blood pressure (SBP)-attained status. METHODS: We divided 1000 subjects with SBP >=180 mm Hg who were randomized within 4.5 hours of symptom onset as follows: SBP <140 mm Hg achieved or not achieved within 2 hours; subjects in whom SBP <140 mm Hg was achieved within 2 hours were further divided: SBP <140 mm Hg for 21 to 22 hours (reduced and maintained) or SBP was >=140 mm Hg for at least 2 hours during the period between 2 and 24 hours (reduced but not maintained). RESULTS: Compared with subjects without reduction of SBP <140 mm Hg within 2 hours, subjects with reduction and maintenance of SBP <140 mm Hg within 2 hours had a similar rate of death or disability (relative risk of 0.98; 95% confidence interval, 0.74-1.29). The rates of neurological deterioration within 24 hours were significantly higher in reduced and maintained group (10.4%; relative risk, 1.98; 95% confidence interval, 1.08-3.62) and in reduced but not maintained group (11.5%; relative risk, 2.08; 95% confidence interval, 1.15-3.75) compared with reference group. The rates of cardiac-related adverse events within 7 days were higher among subjects with reduction and maintenance of SBP <140 mmHg compared to subjects without reduction (11.2% versus 6.4%). CONCLUSIONS: No decline in death or disability but higher rates of neurological deterioration and cardiac-related adverse events were observed among intracerebral hemorrhage subjects with reduction with and without maintenance of intensive SBP goals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565. PMID- 29789396 TI - Patient-Reported Outcome Measures (PROMs) for Acute Stroke: Rationale, Methods and Future Directions. PMID- 29789397 TI - The Wnt antagonist and secreted frizzled-related protein 5: implications on lipid metabolism, inflammation, and type 2 diabetes mellitus. AB - Various reports have suggested that secreted frizzled-related protein (SFRP) 5 (SFRP5) plays a regulatory role in the processes of cellular proliferation and differentiation, by means of inactivating the Wnt/beta-catenin signaling pathway. Recently, SFRP5 has been identified as an anti-inflammatory adipokine, which may be induced during preadipocyte proliferation, differentiation, and maturation. This review aims to identify the recent progress in the research and development of SFRP5 that can play a role in influencing lipid metabolism, inflammation, and type 2 diabetes mellitus (T2DM). Recent evidence has indicated that SFRP5 is capable of stimulating adipocyte differentiation via inhibition of the Wnt/beta catenin signaling pathway. In addition, SFRP5 binding with wingless-type murine mammary tumor virus integration site family, member 5A (Wnt5a), inhibits the activation of c-Jun N-terminal kinase (JNK) downstream of the Wnt signaling pathway. An antagonistic relationship has been found between the reductions in inflammatory cytokine production and serine phosphorylation of insulin receptor substrate-1 (IRS-1) in regard to inhibition of insulin signaling network. By this mechanism, SFRP5 exerts its influence on metabolic function. Based on our review of the current available literature, we support the notion that SFRP5 can be used as a therapeutic target in the treatment of T2DM. PMID- 29789398 TI - MicroRNA-133a impairs perfusion recovery after hindlimb ischemia in diabetic mice. AB - Objective: Peripheral arterial disease (PAD) patients with diabetes mellitus suffer from impaired neovascularization after ischemia which results in poorer outcomes. MicroRNA (miR)-133a is excessively expressed in endothelial cells under diabetic conditions. Here, we test whether diabetes-induced miR-133a up regulation is involved in the impaired capability of neovascularization in experimental PAD models. Methods and results: MiR-133a level was measured by quantitative RT-PCR and showed a higher expression level in the ischemic muscle from diabetic mice when compared with nondiabetic mice. Knockdown of miR-133a using antagomir improved perfusion recovery and angiogenesis in experimental PAD model with diabetes day 21 after HLI. On the other hand, overexpression of miR 133a impaired perfusion recovery. Ischemic muscle was harvested day 7 after experimental PAD for biochemical test, miR-133a antagonism resulted in reduced malondialdehyde, and it increased GTP cyclohydrolase 1 (GCH1), and cyclic guanine monophosphate (cGMP) levels. In cultured endothelial cells, miR-133a antagonism resulted in reduced reactive oxygen species level, and it increased tube formation, nitric oxide (NO), and cGMP level. Moreover, miR-133a antagonism induced angiogenesis was abolished by GCH1 inhibitor. In contrary, miR-133a overexpression impairs angiogenesis and it reduces GCH1, NO, and cGMP levels in nondiabetic models. Conclusion: Diabetes mellitus-induced miR-133a up-regulation impairs angiogenesis in PAD by reducing NO synthesis in endothelial cells. MiR 133a antagonism improves postischemic angiogenesis. PMID- 29789399 TI - EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease for Chinese patients. AB - Objective: Early B-cell factor 1 (EBF1) is a transcription factor that is expressed in early B-cells, adipocytes, and olfactory neurons, and is essential for the maturation of early B lymphocytes. The present study analyzes the influence of EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease (CAD). Methods: In the present study, 243 CAD cases were enrolled as the CAD group and 215 non-CAD patients as the control group by case-control study. We analyzed their genotypes of the rs987401919, rs36071027, and rs1056065671 loci of the EBF1 gene by Sanger sequencing and detected their content of HDL-C, LDL-C, and TG. Results: The C allele at the rs987401919 and rs36071027 loci of EBF1 was found to be the risk factor for CAD (Odds ratio, OR = 1.233; 95% confidence interval, CI: 1.039-1.421; P=0.017; OR = 1.487; 95% CI: 1.015-1.823; P=0.042). The interaction between single nucleotide polymorphisms (SNP) of the rs987401919 and rs36071027 loci and smoking and drinking were distinctly associated with the incidence of CAD (P<0.05). The content of systolic blood pressure (SBP), diastolic blood pressure (DBP), HDL-C, LDL-C, and TG was distinctly changed after gene mutation at the rs987401919 and rs36071027 loci (P<0.05). Conclusion: The results of the present study show that the mutation (CT+TT) at the rs987401919 and rs36071027 loci of EBF1 and its interaction with smoking and drinking are risk factors for CAD, and that the mechanism may be related to the changes in blood pressure and blood lipid content. PMID- 29789401 TI - Treatment with eucalyptol mitigates cigarette smoke-induced lung injury through suppressing ICAM-1 gene expression. AB - The present study was conducted to investigate the clinical significance of Eucalyptol in treating cigarette smoke-induced lung injury with the potential mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) after they were treated with Eucalyptol (260 mg/kg) orally once a day for 12 weeks. Cell counts of bronchoalveolar lavage fluid (BALF), measurements of mean liner intercept (MLI) and mean alveolar number (MAN), and lung function test were executed in experimental animals. Contents of cytokines and intercellular adhesion molecule (ICAM)-1 in BALF and ICAM-1 protein and mRNA expression in lung tissues were determined by ELISA, immunohistochemistry (IHC), and RT-PCR, respectively. A rat model of chronic obstructive pulmonary disease (COPD) displayed declining lung function, increased cell counts and cytokine production in BALF, and emphysema-like lesions in cigarette smoke-exposed lungs compared with the controls (all P<0.01). Treatment with Eucalyptol partly reversed lung function decline with obvious decrease in inflammatory cell infiltrate, TNF-alpha, IL-6, and ICAM-1 expression levels in the challenged lungs (all P<0.05 and 0.01). Furthermore, oral administration of the drug not only reduced the emphysema-associated lung lesions but also suppressed ICAM-1 protein and mRNA expression in the lungs compared with the control (all P<0.05 or 0.01). Intervention of Eucalyptol mitigates the ongoing inflammatory process in airways and ameliorates the cigarette smoke-induced lung injury through suppressing ICAM 1 gene expression in the diseased lungs. PMID- 29789402 TI - Rod-Specific Ablation Using the Nitroreductase/Metronidazole System to Investigate Regeneration in Xenopus. AB - Genetically controlled cell type-specific ablation provides a reproducible method to induce regeneration that can be temporally and spatially controlled. Until recently, regeneration studies in Xenopus have relied on surgical methods to stimulate regeneration. These methods are labor intensive and not as reproducible as a genetically controlled approach. In this protocol we describe selective ablation of rod photoreceptors in the premetamorphic Xenopus laevis retina using the nitroreductase/metronidazole (NTR/Mtz) system. We use the XOPNTR transgenic line in which the Xenopus Rhodopsin promoter drives rod photoreceptor-specific expression of the bacterial enzyme, NTR. Exposure of transgenic tadpoles to Mtz for 2 d completely ablates rods by 7 d after initial Mtz exposure. Removal of Mtz allows rods to regenerate and makes rod-specific ablation reversible and amenable for regeneration studies. The protocol presented here is applicable to the selective ablation of any cell type with the use of appropriate cell type specific promoters. PMID- 29789403 TI - The Mauthner cell in a fish with top-performance and yet flexibly tuned C-starts. I. Identification and comparative morphology. AB - Archerfish use two powerful C-starts: one to escape threats, the other to secure prey that they have downed with a shot of water. The two C-starts are kinematically equivalent and variable in both phases, and the predictive C-starts - used in hunting - are adjusted in terms of the angle of turning and the final linear speed to where and when their prey will hit the water surface. Presently, nothing is known about the neural circuits that drive the archerfish C-starts. As the starting point for a neuroethological analysis, we first explored the presence and morphology of a pair of Mauthner cells, which are key cells in the teleost fast-start system. We show that archerfish have a typical Mauthner cell in each medullary hemisphere and that these send by far the largest axons down the spinal cord. Stimulation of the spinal cord caused short-latency all-or-none field potentials that could be detected even at the surface of the medulla and that had the Mauthner cell as its only source. The archerfish's Mauthner cell is remarkably similar morphologically to that of equally sized goldfish, except that the archerfish's ventral dendrite is slightly longer and its lateral dendrite thinner. Our data provide the necessary starting point for the dissection of the archerfish fast-start system and of any role potentially played by its Mauthner cell in the two C-start manoeuvres. Moreover, they do not support the recently expressed view that Mauthner cells should be reduced in animals with highly variable fast-start manoeuvres. PMID- 29789400 TI - Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma. AB - Carnosic acid (CA), a major polyphenolic diterpene present in Rosmarinus officinalis, has been reported to have multiple functions, including antitumor activity. The MTT assay, BrdU incorporation, wound healing, and colony formation were used to detect melanoma B16F10 cell growth and proliferation. Flow cytometry was used for cell cycle detection. p21 and p27 expression was detected by Western blotting. B16F10 cell xenograft model was established, and treated with CA, carmustine (BCNU), or lomustine (CCNU). The present study found that CA exhibits significant growth inhibition and cell cycle arrest in melanoma B16F10 cells. We also found that CA triggers cell cycle arrest at G0/G1 phase, and enhances p21 expression. Additionally, CA can enhance BCNU- and CCNU-mediated cytotoxicity and cell cycle arrest in B16F10 cells. Finally, we found that CA inhibits tumor growth, and reduces the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in vivo The present study study concluded that CA may be safe and useful as a novel chemotherapeutic agent. PMID- 29789404 TI - New approaches for assessing squid fin motions: coupling proper orthogonal decomposition with volumetric particle tracking velocimetry. AB - Squid, which swim using a coupled fin/jet system powered by muscular hydrostats, pose unique challenges for the study of locomotion. The high flexibility of the fins and complex flow fields generated by distinct propulsion systems require innovative techniques for locomotive assessment. For this study, we used proper orthogonal decomposition (POD) to decouple components of the fin motions and defocusing digital particle tracking velocimetry (DDPTV) to quantify the resultant 3D flow fields. Kinematic footage and DDPTV data were collected from brief squid, Lolliguncula brevis [3.1-6.5 cm dorsal mantle length (DML)], swimming freely in a water tunnel at speeds of 0.39-7.20 DML s-1 Both flap and wave components were present in all fin motions, but the relative importance of the wave components was higher for arms-first swimming than for tail-first swimming and for slower versus higher speed swimming. When prominent wave components were present, more complex interconnected vortex ring wakes were observed, while fin movements dominated by flapping resulted in more spatially separated vortex ring patterns. Although the jet often produced the majority of the thrust for steady rectilinear swimming, our results demonstrated that the fins can contribute more thrust than the jet at times, consistently produce comparable levels of lift to the jet during arms-first swimming, and can boost overall propulsive efficiency. By producing significant drag signatures, the fins can also aid in stabilization and maneuvering. Clearly, fins play multiple roles in squid locomotion, and when coupled with the jet, allow squid to perform a range of swimming behaviors integral to their ecological success. PMID- 29789405 TI - The Mauthner cell in a fish with top-performance and yet flexibly tuned C-starts. II. Physiology. AB - The parallel occurrence in archerfish of fine-tuned and yet powerful predictive C starts as well as of kinematically identical escape C-starts makes archerfish an interesting system to test hypotheses on the roles played by the Mauthner cells, a pair of giant reticulospinal neurons. In this study, we show that the archerfish Mauthner cell shares all hallmark physiological properties with that of goldfish. Visual and acoustic inputs are received by the ventral and lateral dendrite, respectively, and cause complex postsynaptic potentials (PSPs) even in surgically anaesthetised fish. PSP shape did not indicate major differences between the species, but simple light flashes caused larger PSPs in archerfish, often driving the cell to fire an action potential. Probing archerfish in the classical tests for feedback inhibition, established in the Mauthner-associated networks in goldfish, revealed no differences between the two species, including the indications for electrical and chemical synaptic components. Also, the established hallmark experiments on feed-forward inhibition showed no differences between the goldfish and archerfish Mauthner system. Extending these experiments to visual stimuli also failed to detect any differences between the two species and suggested that acoustical and visual input cause feed-forward inhibition, the magnitude, time course and duration of which match that of the respective PSPs in both archerfish and goldfish. Our findings question simple views on the role of the Mauthner cell and suggest that the archerfish Mauthner cell should be a good system to explore the function of these giant neurons in more sophisticated C start behaviours. PMID- 29789406 TI - Ranking hospitals: do we gain reliability by using composite rather than individual indicators? AB - BACKGROUND: Despite widespread use of quality indicators, it remains unclear to what extent they can reliably distinguish hospitals on true differences in performance. Rankability measures what part of variation in performance reflects 'true' hospital differences in outcomes versus random noise. OBJECTIVE: This study sought to assess whether combining data into composites or including data from multiple years improves the reliability of ranking quality indicators for hospital care. METHODS: Using the Dutch National Medical Registration (2007-2012) for stroke, colorectal carcinoma, heart failure, acute myocardial infarction and total hiparthroplasty (THA)/ total knee arthroplasty (TKA) in osteoarthritis (OA), we calculated the rankability for in-hospital mortality, 30-day acute readmission and prolonged length of stay (LOS) for single years and 3-year periods and for a dichotomous and ordinal composite measure in which mortality, readmission and prolonged LOS were combined. Rankability, defined as (between hospital variation/between-hospital+within hospital variation)*100% is classified as low (<50%), moderate (50%-75%) and high (>75%). RESULTS: Admissions from 555 053 patients treated in 95 hospitals were included. The rankability for mortality was generally low or moderate, varying from less than 1% for patients with OA undergoing THA/TKA in 2011 to 71% for stroke in 2010. Rankability for acute readmission was low, except for acute myocardial infarction in 2009 (51%) and 2012 (62%). Rankability for prolonged LOS was at least moderate. Combining multiple years improved rankability but still remained low in eight cases for both mortality and acute readmission. Combining the individual indicators into the dichotomous composite, all diagnoses had at least moderate rankability (range: 51%-96%). For the ordinal composite, only heart failure had low rankability (46% in 2008) (range: 46%-95%). CONCLUSION: Combining multiple years or into multiple indicators results in more reliable ranking of hospitals, particularly compared with mortality and acute readmission in single years, thereby improving the ability to detect true hospital differences. The composite measures provide more information and more reliable rankings than combining multiple years of individual indicators. PMID- 29789407 TI - Immediate and long-term effects of a team-based quality improvement training programme. AB - BACKGROUND: Although many studies of quality improvement (QI) education programmes report improvement in learners' knowledge and confidence, the impact on learners' future engagement in QI activities is largely unknown and few studies report project measures beyond completion of the programme. METHOD: We developed the Academy for Quality and Safety Improvement (AQSI) to prepare individuals, across multiple departments and professions, to lead QI. The 7-month programme consisted of class work and team-based project work. We assessed participants' knowledge using a multiple choice test and an adapted Quality Improvement Knowledge Assessment Test (QIKAT) before and after the programme. We evaluated participants' postprogramme QI activity and project status using surveys at 6 and 18 months. RESULTS: Over 5 years, 172 individuals and 32 teams participated. Participants had higher multiple choice test (71.9+/-12.7 vs 79.4+/ 13.2; p<0.001) and adapted QIKAT scores (55.7+/-16.3 vs 61.8+/-14.7; p<0.001) after the programme. The majority of participants at 6 months indicated that they had applied knowledge and skills learnt to improve quality in their clinical area (129/148; 87.2%) and to implement QI interventions (92/148; 62.2%). At 18 months, nearly half (48/101; 47.5%) had led other QI projects and many (41/101; 40.6%) had provided QI mentorship to others. Overall, 14 (43.8%) teams had positive postintervention results at AQSI completion and 20 (62.5%) had positive results at some point (ie, completion, 6 months or 18 months after AQSI). CONCLUSIONS: A team-based QI training programme resulted in a high degree of participants' involvement in QI activities beyond completion of the programme. A majority of team projects showed improvement in project measures, often occurring after completion of the programme. PMID- 29789408 TI - The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women. AB - OBJECTIVE: Human aging is accompanied by a decrease in growth hormone secretion and serum insulin-like growth factor (IGF)-1 levels. Also, loss of muscle mass and strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community-dwelling elderly. DESIGN: Observational cohort study (cross-sectional and prospective). METHODS: We studied the association between IGF-1 and handgrip strength, physical performance and falls in participants of the Longitudinal Aging Study Amsterdam. A total of 1292 participants were included (633 men, 659 women). Serum IGF-1 levels were divided into quartiles (IGF-1-Q1 to IGF-1-Q4). Data on falls were collected prospectively for a period of 3 years. All analyses were stratified for age and physical activity and adjusted for relevant confounders. RESULTS: Men with a low physical activity score in IGF-1-Q1 and IGF 1-Q2 of the younger age group had a lower handgrip strength compared to IGF-1-Q4. In younger more active males in IGF-1-Q2 physical performance was worse. Recurrent fallers were less prevalent in older, low active males with low IGF-1 levels. In females, recurrent fallers were more prevalent in older, more active females in IGF-1-Q2. IGF-1 quartile may predict changes in handgrip strength and physical performance in men and women. CONCLUSIONS: Our results indicate that lower IGF-1 levels are associated with lower handgrip strength and worse physical performance, but less recurrent fallers especially in men. Associations were often more robust in IGF-1-Q2. Future studies on this topic are desirable. PMID- 29789409 TI - Characterization of an activating R1353H insulin-like growth factor 1 receptor variant in a male with extreme tall height. AB - OBJECTIVE: The insulin-like growth factor1 receptor (IGF1R) is important in growth and development, and inactivating IGF1R mutations cause short stature and relatively high levels of serum IGF-I. We identified an unclassified IGF1RR1353H variant in a male with extreme tall height, very low levels of serum IGF-I and delayed and prolonged growth spurt. The index case's mother and three sons all carried the variant, but so far only the eldest son (age 18 years) presented with tall height. We hypothesized that the variant could constitute an activating mutation. DESIGN: The IGF1RR1353H variant was investigated in Igf1r-/- mouse embryonic fibroblasts (R-cells) by cell cycle, colony formation and transcriptome analyses. RESULTS: The IGF1RR1353H (R-1353) exhibited significantly increased cell proliferation, G1-S progression and colony formation in soft agar. RNA sequencing identified 195 differentially expressed genes between R-WT and R-1353 (adjusted P < 1E-100). Most genes were upregulated in R-1353, including the gene encoding the androgen receptor (AR). Gene expression profiling showed the most significant enrichment in extracellular matrix organization (P = 2.76E-7), collagen biosynthesis (P = 1.21E-5) and cell adhesion (P = 7.38E-5). Retrospective biochemical analysis of the index case revealed decreased testosterone and sex hormone-binding globulin levels, whereas LH and FSH were within normal ranges. This profile suggests an increased sensitivity to androgen, which is compatible with the enhanced expression of Ar in R-1353 cells. CONCLUSIONS: Our findings suggest that R1353H constitutes an activating IGF1R variant. The possible deregulation of collagen turnover and increased androgen sensitivity implicates an association to tall phenotype in male carriers. PMID- 29789411 TI - Heliox Adjunct Therapy for Neonates With Congenital Diaphragmatic Hernia. AB - BACKGROUND: Congenital diaphragmatic hernia remains a complex disease with significant morbidity and mortality. Hypercarbia is a common derangement in this population, which often requires escalating ventilator support. By decreasing airway turbulence and enhancing CO2 removal, inhaled helium-oxygen mixture (heliox) has the potential to improve ventilation and thereby decrease ventilator support and its associated lung injury. METHODS: Retrospective cohort review of all neonates with congenital diaphragmatic hernia treated at Rady Children's Hospital San Diego during 2011-2015. Clinical characteristics were compared between the infants who were treated with heliox and those who did not receive this intervention. To analyze the effect of heliox in the subgroup that received this treatment, ventilator settings and arterial blood gas values were compared before and after starting heliox by using paired t tests. RESULTS: During the study period, 45 neonates with congenital diaphragmatic hernia were admitted to our neonatal ICU, 28 received heliox, and 27 were analyzed. During heliox treatment, PaCO2 levels decreased from 68 to 49 mm Hg (P < .001), amplitude decreased from 33 to 23 cm H2O (P < .001), ventilator frequency decreased from 28 to 23 breaths/min (P = .02), FIO2 decreased from 0.52 to 0.40 (P < .01), and pH increased from 7.3 to 7.4 (P < .001). CONCLUSIONS: The addition of heliox to the standard practice of permissive hypercapnia facilitated improvement in gas exchange, which allowed a decrease in ventilator settings and oxygen exposure, both of which are known to contribute to lung injury in this population. A prospective trial is needed to more clearly define the acute and long-term impacts of this treatment. PMID- 29789412 TI - Effect of a Nebulizer Holding Chamber on Aerosol Delivery. AB - BACKGROUND: A new holding chamber was designed to be used with the Aerogen Solo nebulizer to increase the aerosol emitted that reach the patient. The aim of this study was to evaluate the efficacy of this holding chamber with the nebulizer and determine its usability with other nebulizers. METHODS: The study was divided into 2 parts. In the first part, aerosol emitted of 1 mL respirable solution (nominal dose of 5000 MUg salbutamol), delivered by using the mesh nebulizer, Pro nebulizer, and jet nebulizer, connected to a T-piece or a holding chamber, was determined by using a breathing simulator set to provide a tidal volume of 500 mL, frequency of 15 breaths/min, and the inspiratory-expiratory ratio of 1:1 for adults as the quiet breathing pattern. Aerodynamic particle size characterizations were determined by using a cooled cascade impactor at an inhalation flow of 15 L/min. In the second part of the study, 12 healthy nonsmoking subjects (6 females) >18 y, with an FEV1 > 90% were enrolled. Inhaled aerosol of 1 mL respirable solution (5,000 MUg salbutamol) was delivered through the mesh nebulizer-holding chamber and an mesh nebulizer-T-piece using normal tidal breathing. The subjects provided urine samples 30 min after dosing and cumulatively collected their urine for 24 h. The samples were analyzed for salbutamol content. RESULTS: The holding chamber significantly increased aerosol emitted by the 3 nebulizers compared with the T-piece (P < .01) and relatively decreased the mass median aerodynamic diameter but with no significant difference. The mesh nebulizer-holding chamber resulted in significantly higher aerosol emitted compared with any other delivery method tested (P < .01). The mesh nebulizer-holding chamber resulted in higher urine samples 30 min after dosing (as an index of lung deposition) and cumulatively collected urine for 24 h (as an index of systemic absorption) compared with the nebulizer-T-piece (P < .05). CONCLUSIONS: The use of the holding chamber with a jet nebulizer, Pro nebulizer, and the Solo nebulizer significantly increased the aerosol delivery. The Solo nebulizer-holding chamber had the highest aerosol emitted compared with all nebulizer-adapter combinations and higher urine samples 30 min after dosing and cumulatively collected urine for 24 h compared with the nebulizer-T-piece. PMID- 29789410 TI - A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly. AB - OBJECTIVE: ATL1103 is a second-generation antisense oligomer targeting the human growth hormone (GH) receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. DESIGN: Twenty-six patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once or twice weekly for 13 weeks and monitored for a further 8-week washout period. METHODS: The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, acid labile subunit (ALS), GH, growth hormone-binding protein (GHBP)), comparison was between baseline and week 14. Safety was assessed by reported adverse events. RESULTS AND CONCLUSIONS: Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups respectively. Compared to baseline, at week 14, twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (P = 0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (P = 0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and remained lower at week 21 than at baseline by a median of 18.7% (P = 0.0005). Compared to baseline, by week 14, IGFBP3 and ALS had declined by a median of 8.9% (P = 0.027) and 16.7% (P = 0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (P = 0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (P = 0.027 and P = 0.005) respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild-to-moderate injection-site reactions. This study provides proof of concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly. PMID- 29789413 TI - Best Protocol for the Sit-to-Stand Test in Subjects With COPD. AB - BACKGROUND: Different protocols for the sit-to-stand test (STS) are available for assessing functional capacity in COPD. We sought to correlate each protocol of the STS (ie, the 5-repetition [5-rep STS], the 30-s STS, and the 1-min STS) with clinical outcomes in subjects with COPD. We also aimed to compare the 3 protocols of the STS, to verify their association and agreement, and to verify whether the 3 protocols are able to predict functional exercise capacity and physical activity in daily life (PADL). METHODS: 23 subjects with COPD (11 men; FEV1 53 +/ 15% predicted) performed 3 protocols of the STS. Subjects also underwent the following assessments: incremental shuttle walking test, 6-min walk test (6MWT), 4-m gait speed test (4MGS), 1-repetition maximum of quadriceps muscle, assessment of PADL, and questionnaires on health-related quality of life and functional status. RESULTS: The 1-min STS showed significant correlations with the 6MWT (r = 0.40), 4MGS (r = 0.64), and PADL (0.40 <= r <= 0.52), and the 5-rep STS and 30-s STS were associated with the 4MGS (r = 0.54 and r = 0.52, respectively). The speed differed for each protocol (5-rep STS 0.53 +/- 0.16 rep/s, 30-s STS 0.48 +/ 0.13 rep/s, 1-min STS 0.45 +/- 0.11 rep/s, P = .01). However, they presented good agreement (intraclass correlation coefficient >= 0.73 for all) and correlated well with each other (r >= 0.68 for all). More marked changes in peripheral oxygen saturation (P = .004), heart rate (P < .001), blood pressure (P < .001), dyspnea (P < .001), and leg fatigue (P < .001) were found after the 1 min STS protocol. Furthermore, the 3 protocols were equally able to identify subjects with low exercise capacity or preserved exercise capacity. CONCLUSIONS: The 1-min STS generated higher hemodynamic demands and correlated better with clinical outcomes in subjects with COPD. Despite the difference in speed performance and physiological demands between the 5-rep STS and 1-min STS, there was a good level of agreement among the 3 protocols. In addition, all 3 tests were able to identify subjects with low exercise capacity or preserved exercise capacity. PMID- 29789414 TI - Development of Personalized Fitting Device With 3-Dimensional Solution for Prevention of NIV Oronasal Mask-Related Pressure Ulcers. AB - BACKGROUND: Pressure ulcers related to oronasal masks used with noninvasive ventilation (NIV), along with patient discomfort, occur due to improper fit of the mask. We developed a personalized fitting device using a 3-dimensional (3D) scanning solution to prevent the formation of NIV mask-related pressure ulcers. This study aimed to evaluate the effectiveness of the proposed personalized fitting device. METHODS: We conducted a randomized crossover experimental study of 20 healthy participants to study the use of this personalized fitting device between the face and an NIV mask designed with 3D solutions. The fitting device was not used under the NIV mask for the control. The outcome measures were the presence of blanchable erythema, standardized redness intensity, discomfort level, and contact pressure. RESULTS: The incidence of blanchable erythema and standardized redness intensity values were significantly lower for subjects who used the fitting device when worn for 30 min (P < .001). The discomfort levels at the forehead, nasal bridge, and both cheeks, as well as leakage, were significantly reduced as well (P = .008, P < .001, P = .001, P = .002, P = .001, P = .02, P < .001, P < .001, P < .001). Contact pressure at the nasal bridge, where pressure ulcers most frequently develop, was significantly decreased with the fitting device (P < .001). CONCLUSIONS: Personalized fitting devices that incorporate 3D scanning solutions may contribute to the prevention of NIV mask related pressure ulcers and the reduction of discomfort. PMID- 29789415 TI - Acute Effects of Different Types of Resistance Training on Cardiac Autonomic Modulation in COPD. AB - BACKGROUND: An exercise modality that has been gaining significant importance in the rehabilitation of subjects with COPD is resistance training. When considering that patients with COPD present alterations in autonomic cardiac modulation caused by the disease itself, it is necessary to investigate the behavior of the autonomic nervous system in relation to this type of exercise. Thus, the objective of this study was to compare the acute effects of resistance training with elastic tubes, elastic bands, and conventional weightlifitng on the behavior of cardiac autonomic modulation in post-exercise recovery in subjects with COPD. METHODS: Thirty-four subjects with COPD performed an single session of resistance training divided according to the therapeutic resource used: elastic tubes (n = 10), elastic bands (n = 11), and conventional bodybuilding (n = 13). For analysis of cardiac autonomic modulation, the heart rate was obtained beat to beat at rest and immediately after the end of the session for 60 min in a seated position. Heart rate variability indices were obtained in the time and frequency domains. RESULTS: The 3 therapeutic resource types used in the single session of resistance training promoted changes in heart rate variability linear indices in the time and frequency domains; however, post-exercise recovery time was similar for all protocols performed. CONCLUSIONS: After single resistance training the elastic tubes group presented a minimum alteration in the post-exercise recovery of cardiac autonomic modulation in the subjects with COPD; however, at 5 min after exercising, the subjects with COPD had already recovered. Therefore, if the purpose of the training is to restore autonomic cardiac modulation, the use of elastic tubes is suggested, when considering their low cost and versatility. PMID- 29789416 TI - Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer. AB - The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study, we find that macrophage-derived granulin contributes to cytotoxic CD8+ T-cell exclusion in metastatic livers. Granulin expression by macrophages was induced in response to colony-stimulating factor 1. Genetic depletion of granulin reduced the formation of a fibrotic stroma, thereby allowing T-cell entry at the metastatic site. Although metastatic PDAC tumors are largely resistant to anti-PD-1 therapy, blockade of PD-1 in granulin-depleted tumors restored the antitumor immune defense and dramatically decreased metastatic tumor burden. These findings suggest that targeting granulin may serve as a potential therapeutic strategy to restore CD8+ T-cell infiltration in metastatic PDAC, thereby converting PDAC metastatic tumors, which are refractory to immune checkpoint inhibitors, into tumors that respond to immune checkpoint inhibition therapies.Significance: These findings uncover a mechanism by which metastatic PDAC tumors evade the immune response and provide the rationale for targeting granulin in combination with immune checkpoint inhibitors for the treatment of metastatic PDAC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4253/F1.large.jpg Cancer Res; 78(15); 4253-69. (c)2018 AACR. PMID- 29789418 TI - Juxtacrine Signaling Inhibits Antitumor Immunity by Upregulating PD-L1 Expression. AB - Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1 targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact induced signaling in cancer immunity. Here, we show that tumor cell contact upregulates PD-L1 expression and reduces T-cell-mediated cell killing through the membrane receptor tyrosine kinase ephrin receptor A10 (EphA10), which is not expressed in normal tissues except testis and is known to mediate cell contact dependent juxtacrine signaling. Knockout of EphA10 in tumor cells increased T cell-mediated antitumor immunity in syngeneic mouse models. EphA10 expression also correlated positively with PD-L1 in human breast tumor tissues. Together, our data reveal that in addition to paracrine/autocrine signaling, cell contact mediated juxtacrine signaling also promotes PD-L1 expression, implying that tumor cells may escape immune surveillance via this mechanism and that targeting EphA10 to boost antitumor immunity may be a new immune checkpoint blockade strategy for female patients with breast cancer.Significance: Regulation of PD-L1 expression by cell contact-mediated signaling promotes immune escape in breast cancer and may lead to the development of an immunotherapy with less adverse effects in female patients. Cancer Res; 78(14); 3761-8. (c)2018 AACR. PMID- 29789419 TI - Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells. AB - The increasing incidence of bladder cancer and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention; however, they suffer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETC), either individually or in clusters, in a clean and segregated environment, which is crucial to minimize cross-contamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression, and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 patients with bladder cancer and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably higher UETC counts in patients with bladder cancer versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; P < 0.0001]. For bladder cancer detection, a stratified 10-fold cross-validation of training data reveals an overall predictive accuracy of 0.84 [95% confidence interval (CI), 0.76-0.93] with an 89.8% (95% CI, 71.5%-86.4%) for sensitivity and 71.5% (95% CI, 59.7%-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity compared with other techniques for the detection of bladder cancer.Significance: A unique and promising diagnostic assay for bladder cancer is proposed with potential clinical utility as a complement for cytology. Cancer Res; 78(14); 4073 85. (c)2018 AACR. PMID- 29789417 TI - Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation. AB - Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma-associated pathways, including Wnt, TGFbeta, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627-41. (c)2018 AACR. PMID- 29789420 TI - Glycosylation of Recombinant Anticancer Therapeutics in Different Expression Systems with Emerging Technologies. AB - Glycosylation, a posttranslational modification, has a major role in recombinant anticancer therapeutic proteins, as most of the approved recombinant therapeutics are glycoproteins. The constant amino acid sequence of therapeutics determines the enzymatic activity, while the presence of glycans influences their pharmacokinetics, solubility, distribution, serum half-life, effector function, and binding to receptors. Glycoproteins expressed in different expression systems acquire their own oligosaccharides, which increases the protein diversity. The heterogeneity of glycans creates hurdles in downstream processing, ultimately leading to variable anticancer therapeutic efficacy. Therefore, glycoproteins require an appropriate expression system to obtain structurally and functionally identical glycans, as in humans. In many expression systems, the N-glycosylation pathway remains conserved in the endoplasmic reticulum, but divergence is observed when the protein enters the Golgi complex. Hence, in recent decades, numerous approaches have been adopted to engineer the Golgi's N-glycosylation pathway to attain human-like glycans. Several researchers have tried to engineer the N-glycosylation pathway of expression systems. In this review, we examine the glycosylation pattern in various expression systems, along with emerging technologies for glycosylation engineering of anticancer therapeutic drugs. Cancer Res; 78(11); 2787-98. (c)2018 AACR. PMID- 29789422 TI - Machine Learning-Based Radiomics for Molecular Subtyping of Gliomas. AB - Purpose: The new classification announced by the World Health Organization in 2016 recognized five molecular subtypes of diffuse gliomas based on isocitrate dehydrogenase (IDH) and 1p/19q genotypes in addition to histologic phenotypes. We aim to determine whether clinical MRI can stratify these molecular subtypes to benefit the diagnosis and monitoring of gliomas.Experimental Design: The data from 456 subjects with gliomas were obtained from The Cancer Imaging Archive. Overall, 214 subjects, including 106 cases of glioblastomas and 108 cases of lower grade gliomas with preoperative MRI, survival data, histology, IDH, and 1p/19q status were included. We proposed a three-level machine-learning model based on multimodal MR radiomics to classify glioma subtypes. An independent dataset with 70 glioma subjects was further collected to verify the model performance.Results: The IDH and 1p/19q status of gliomas can be classified by radiomics and machine-learning approaches, with areas under ROC curves between 0.922 and 0.975 and accuracies between 87.7% and 96.1% estimated on the training dataset. The test on the validation dataset showed a comparable model performance with that on the training dataset, suggesting the efficacy of the trained classifiers. The classification of 5 molecular subtypes solely based on the MR phenotypes achieved an 81.8% accuracy, and a higher accuracy of 89.2% could be achieved if the histology diagnosis is available.Conclusions: The MR radiomics based method provides a reliable alternative to determine the histology and molecular subtypes of gliomas. Clin Cancer Res; 24(18); 4429-36. (c)2018 AACR. PMID- 29789421 TI - Pericytes in the Premetastatic Niche. AB - The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779-86. (c)2018 AACR. PMID- 29789424 TI - The C-terminal region of the yeast monocarboxylate transporter Jen1 acts as a glucose signal-responding degron recognized by the alpha-arrestin Rod1. AB - In response to changes in nutrient conditions, cells rearrange the composition of plasma membrane (PM) transporters to optimize their metabolic flux. Not only transcriptional gene regulation, but also inactivation of specific transporters is important for fast rearrangement of the PM. In eukaryotic cells, endocytosis plays a role in transporter inactivation, which is triggered by ubiquitination of these transporters. The Nedd4 family E3 ubiquitin ligase is responsible for ubiquitination of the PM transporters and requires that a series of alpha arrestin proteins are targeted to these transporters. The mechanism by which an alpha-arrestin recognizes its cognate transporters in response to environmental signals is of intense scientific interest. Excess substrates or signal transduction pathways are known to initiate recognition of transporters by alpha arrestins. Here, we identified an endocytic-sorting signal in the monocarboxylate transporter Jen1 from yeast (Saccharomyces cerevisiae), whose endocytic degradation depends on the Snf1-glucose signaling pathway. We found that the C terminal 20-amino acid-long region of Jen1 contains an amino acid sequence required for association of Jen1 to the alpha-arrestin Rod1, as well as lysine residues important for glucose-induced Jen1 ubiquitination. Notably, fusion of this region to the methionine permease, Mup1, whose endocytosis is normally induced by excess methionine, was sufficient for Mup1 to undergo glucose-induced, Rod1-mediated endocytosis. Taken together, our results demonstrate that the Jen1 C-terminal region acts as a glucose-responding degron for alpha-arrestin-mediated endocytic degradation of Jen1. PMID- 29789423 TI - ATP-binding cassette member B5 (ABCB5) promotes tumor cell invasiveness in human colorectal cancer. AB - ABC member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression. In human-to-mouse CRC tumor xenotransplantation models that exhibited circulating tumor mRNA, we observed that cancer-specific ABCB5 knockdown significantly reduced detection of these transcripts, suggesting that the knockdown inhibited tumor invasiveness. Mechanistically, this effect was associated with inhibition of expression and downstream signaling of AXL receptor tyrosine kinase (AXL), a proinvasive molecule herein shown to be produced by ABCB5-positive CRC cells. Importantly, rescue of AXL expression in ABCB5 knockdown CRC tumor cells restored tumor-specific transcript detection in the peripheral blood of xenograft recipients, indicating that ABCB5 regulates CRC invasiveness, at least in part, by enhancing AXL signaling. Our results implicate ABCB5 as a critical determinant of CRC invasiveness and suggest that ABCB5 blockade might represent a strategy in CRC therapy, even independently of ABCB5's function as an MDR mediator. PMID- 29789425 TI - A heterodimer formed by bone morphogenetic protein 9 (BMP9) and BMP10 provides most BMP biological activity in plasma. AB - Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1. Next, we developed an ELISA that could specifically recognize the BMP9-BMP10 heterodimer and which indicated its presence in both human and mouse plasma. In addition to using available Bmp9-KO mice, we generated a conditional Bmp10-KO mouse strain. The plasma from Bmp10-KO mice, similarly to that of Bmp9-KO mice, completely lacked the ability to activate ALK1-transfected 3T3 cells or phospho-Smad1-5 on endothelial cells, indicating that the circulating BMP activity is mostly due to the BMP9-BMP10 heterodimeric form. This result was confirmed in human plasma that had undergone affinity chromatography to remove BMP9 homodimer. Finally, we provide evidence that hepatic stellate cells in the liver could be the source of the BMP9-BMP10 heterodimer. Together, our findings demonstrate that BMP9 and BMP10 can heterodimerize and that this heterodimer is responsible for most of the biological BMP activity found in plasma. PMID- 29789426 TI - JAK1-mediated Sirt1 phosphorylation functions as a negative feedback of the JAK1 STAT3 pathway. AB - The type III NAD-dependent histone deacetylase Sirt1 plays important roles in a variety of pathobiological functions through targeting either the acetylated histones or transcription factors. However, the molecular mechanisms underlying how the Sirt1 functions are regulated remain vague. Herein we identified that the Janus kinase 1 (JAK1) interacts with Sirt1 and catalyzes its phosphorylation at the tyrosine residues of 280 and 301, both of which are highly conserved and located in the histone deacetylase catalytic domain of Sirt1. IL-6 stimulation enhanced Sirt1 interaction with JAK1 and JAK1-mediated Sirt1 phosphorylation. Interestingly, JAK1-mediated Sirt1 phosphorylation did not alter Sirt1 deacetylase catalytic activity, but instead it is required for Sirt1 interaction with the downstream transcription factor STAT3. JAK1-mediated phosphorylation enhanced Sirt1 suppression of STAT3 acetylation and transcriptional activity. As a consequence, Sirt1 activation attenuates IL-6 activity in protecting cancer cells from chemotherapeutic drug-induced apoptosis. Our studies identify JAK1 as a previously unappreciated tyrosine kinase of Sirt1 and reveal a novel negative feedback of the JAK1-STAT3 pathway. PMID- 29789428 TI - Injury prevention: achieving population-level change. PMID- 29789427 TI - Impact of tobacco-specific nitrosamine-derived DNA adducts on the efficiency and fidelity of DNA replication in human cells. AB - The tobacco-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are known human carcinogens. Following metabolic activation, NNK and NNN can induce a number of DNA lesions, including several 4-(3-pyridyl)-4-oxobut-1-yl (POB) adducts. However, it remains unclear to what extent these lesions affect the efficiency and accuracy of DNA replication and how their replicative bypass is influenced by translesion synthesis (TLS) DNA polymerases. In this study, we investigated the effects of three stable POB DNA adducts (O2-POB-dT, O4-POB-dT, and O6-POB-dG) on the efficiency and fidelity of DNA replication in HEK293T human cells. We found that, when situated in a double stranded plasmid, O2-POB-dT and O4-POB-dT moderately blocked DNA replication and induced exclusively T->A (~14.9%) and T->C (~35.2%) mutations, respectively. On the other hand, O6-POB-dG slightly impeded DNA replication, and this lesion elicited primarily the G->A transition (~75%) together with a low frequency of the G->T transversion (~3%). By conducting replication studies in isogenic cells in which specific TLS DNA polymerases (Pols) were deleted by CRISPR-Cas9 genome editing, we observed that multiple TLS Pols, especially Pol eta and Pol zeta, are involved in bypassing these lesions. Our findings reveal the cytotoxic and mutagenic properties of specific POB DNA adducts and unravel the roles of several TLS polymerases in the replicative bypass of these adducts in human cells. Together, these results provide important new knowledge about the biological consequences of POB adducts. PMID- 29789429 TI - Brown adipose tissue development and function and its impact on reproduction. AB - Although brown adipose tissue (BAT) is one of the smallest organs in the body, it has the potential to have a substantial impact on both heat production as well as fat and carbohydrate metabolism. This is most apparent at birth, which is characterised with the rapid appearance and activation of the BAT specific mitochondrial uncoupling protein (UCP)1 in many large mammals. The amount of brown fat then gradually declines with age, an adaptation that can be modulated by the thermal environment. Given the increased incidence of maternal obesity and its potential transmission to the mother's offspring, increasing BAT activity in the mother could be one mechanism to prevent this cycle. To date, however, all rodent studies investigating maternal obesity have been conducted at standard laboratory temperature (21 degrees C), which represents an appreciable cold challenge. This could also explain why offspring weight is rarely increased, suggesting that future studies would benefit from being conducted at thermoneutrality (~28 degrees C). It is also becoming apparent that each fat depot has a unique transcriptome and show different developmental pattern, which is not readily apparent macroscopically. These differences could contribute to the retention of UCP1 within the supraclavicular fat depot, the most active depot in adult humans, increasing heat production following a meal. Despite the rapid increase in publications on BAT over the past decade, the extent to which modifications in diet and/or environment can be utilised to promote its activity in the mother and/or her offspring remains to be established. PMID- 29789430 TI - Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. AB - Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and >=85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15 <29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean+/-SEM follow-up of 3.4+/-2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75 84, and >=85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients. PMID- 29789432 TI - GATM Mutations Cause a Dominant Fibrillar Conformational Disease in Mitochondria When Eternity Kills. PMID- 29789431 TI - Clinical and Pathology Findings Associate Consistently with Larger Glomerular Volume. AB - Background Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities.Methods We studied kidney biopsy specimens from living kidney donors (n=2453) and patients who underwent radical nephrectomy for a renal tumor (n=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel-Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen.Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (P<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume.Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity. PMID- 29789433 TI - Retraction for Hunter et al., "Lactobacillus bulgaricus Prevents Intestinal Epithelial Cell Injury Caused by Enterobacter sakazakii-Induced Nitric Oxide both In Vitro and in the Newborn Rat Model of Necrotizing Enterocolitis". PMID- 29789434 TI - Erratum for Graham-Brown et al., "Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation". PMID- 29789436 TI - Low Vulnerability to Xylem Embolism in Leaves and Stems of North American Oaks. AB - Although recent findings suggest that xylem embolism represents a significant, drought-induced damaging process in land plants, substantial debate surrounds the capacity of long-vesseled, ring-porous species to resist embolism. We investigated whether recent methodological developments could help resolve this controversy within Quercus, a long-vesseled, ring-porous temperate angiosperm genus, and shed further light on the importance of xylem vulnerability to embolism as an indicator of drought tolerance. We used the optical technique to quantify leaf and stem xylem vulnerability to embolism of eight Quercus species from the Mediterranean-type climate region of California to examine absolute measures of resistance to embolism as well as any potential hydraulic segmentation between tissue types. We demonstrated that our optical assessment reflected flow impairment for a subset of our sample species by quantifying changes in leaf hydraulic conductance in dehydrating branches. Air-entry water potential varied 2-fold in leaves, ranging from -1.7 +/- 0.25 MPa to -3.74 +/- 0.23 MPa, and 4-fold in stems, ranging from -1.17 +/- 0.04 MPa to -4.91 +/- 0.3 MPa. Embolism occurred earlier in leaves than in stems in only one out of eight sample species, and plants always lost turgor before experiencing stem embolism. Our results show that long-vesseled North American Quercus species are more resistant to embolism than previously thought and support the hypothesis that avoiding stem embolism is a critical component of drought tolerance in woody trees. Accurately quantifying xylem vulnerability to embolism is essential for understanding species distributions along aridity gradients and predicting plant mortality during drought. PMID- 29789437 TI - Dynamics of RecA-mediated repair of replication-dependent DNA breaks. AB - Chromosomal replication is the major source of spontaneous DNA double-strand breaks (DSBs) in living cells. Repair of these DSBs is essential for cell viability, and accuracy of repair is critical to avoid chromosomal rearrangements. Repair of replication-dependent DSBs occurs primarily by homologous recombination with a sister chromosome. However, this reaction has never been visualized at a defined chromosomal locus, so little is known about its spatial or temporal dynamics. Repair of a replication-independent DSB generated in Escherichia coli by a rare-cutting endonuclease leads to the formation of a bundle of RecA filaments. In this study, we show that in contrast, repair of a replication-dependent DSB involves a transient RecA focus localized in the central region of the cell in which the DNA is replicated. The recombining loci remain centrally located with restricted movement before segregating with little extension to the period of postreplicative sister-chromosome cohesion. The spatial and temporal efficiency of this reaction is remarkable. PMID- 29789435 TI - Molecular Mechanisms Preventing Senescence in Response to Prolonged Darkness in a Desiccation-Tolerant Plant. AB - The desiccation-tolerant plant Haberlea rhodopensis can withstand months of darkness without any visible senescence. Here, we investigated the molecular mechanisms of this adaptation to prolonged (30 d) darkness and subsequent return to light. H. rhodopensis plants remained green and viable throughout the dark treatment. Transcriptomic analysis revealed that darkness regulated several transcription factor (TF) genes. Stress- and autophagy-related TFs such as ERF8, HSFA2b, RD26, TGA1, and WRKY33 were up-regulated, while chloroplast- and flowering-related TFs such as ATH1, COL2, COL4, RL1, and PTAC7 were repressed. PHYTOCHROME INTERACTING FACTOR4, a negative regulator of photomorphogenesis and promoter of senescence, also was down-regulated. In response to darkness, most of the photosynthesis- and photorespiratory-related genes were strongly down regulated, while genes related to autophagy were up-regulated. This occurred concomitant with the induction of SUCROSE NON-FERMENTING1-RELATED PROTEIN KINASES (SnRK1) signaling pathway genes, which regulate responses to stress-induced starvation and autophagy. Most of the genes associated with chlorophyll catabolism, which are induced by darkness in dark-senescing species, were either unregulated (PHEOPHORBIDE A OXYGENASE, PAO; RED CHLOROPHYLL CATABOLITE REDUCTASE, RCCR) or repressed (STAY GREEN-LIKE, PHEOPHYTINASE, and NON-YELLOW COLORING1). Metabolite profiling revealed increases in the levels of many amino acids in darkness, suggesting increased protein degradation. In darkness, levels of the chloroplastic lipids digalactosyldiacylglycerol, monogalactosyldiacylglycerol, phosphatidylglycerol, and sulfoquinovosyldiacylglycerol decreased, while those of storage triacylglycerols increased, suggesting degradation of chloroplast membrane lipids and their conversion to triacylglycerols for use as energy and carbon sources. Collectively, these data show a coordinated response to darkness, including repression of photosynthetic, photorespiratory, flowering, and chlorophyll catabolic genes, induction of autophagy and SnRK1 pathways, and metabolic reconfigurations that enable survival under prolonged darkness. PMID- 29789440 TI - Objective evaluation of ram and buck sperm motility by using a novel sperm tracker software. AB - This work offers researchers the first version of an open-source sperm tracker software (Sperm Motility Tracker, V1.0) containing a novel suit of algorithms to analyze sperm motility using ram and buck sperm as models. The computer-assisted semen analysis is used in several publications with increasing trend worldwide in the last years, showing the importance of objective methodologies to evaluate semen quality. However, commercial systems are costly and versatility is constrained. In the proposed method, segmentation is applied and the tracking stage is performed by using individual Kalman filters and a simplified occlusion handling method. The tracking performance in terms of precision (number of true tracks), the percentage of fragmented paths and percentage of correctly detected particles were manually validated by three experts and compared with the performance of a commercial motility analyzer (Microptic's SCA). The precision obtained with our sperm motility tracker was higher than the one obtained with a commercial software at the current acquisition frame rate of 25 fps (P < 0.0001), concomitantly with a similar percentage of fragmentized tracks (P = 0.0709) at sperm concentrations ranging 25-37 * 106 cells/mL. Moreover, our tracker was able to detect trajectories that were unseen by SCA. Kinetic values obtained by using both methods were contrasted. The higher values found were explained based on the better performance of our sperm tracker to report speed parameters for very fast motile sperm. To standardize results, acquisition conditions are suggested. This open-source sperm tracker software has a good plasticity allowing researchers to upgrade according requirements and to apply the tool for sperm from a variety of species. PMID- 29789439 TI - Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. AB - Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome-lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells. By screening other human SNAREs, we identified YKT6 as a novel autophagosomal SNARE protein. Depletion of YKT6 inhibited autophagosome-lysosome fusion partially in wild-type and completely in STX17 KO cells, suggesting that YKT6 and STX17 are independently required for fusion. YKT6 formed a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. Recruitment of YKT6 to autophagosomes depends on its N terminal longin domain but not on the C-terminal palmitoylation and farnesylation that are essential for its Golgi localization. These findings suggest that two independent SNARE complexes mediate autophagosome-lysosome fusion. PMID- 29789438 TI - Integrin alpha4beta7 switches its ligand specificity via distinct conformer specific activation. AB - Chemokine (C-C motif) ligand 25 (CCL25) and C-X-C motif chemokine 10 (CXCL10) induce the ligand-specific activation of integrin alpha4beta7 to mediate the selective adhesion of lymphocytes to mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) or vascular cell adhesion molecule-1 (VCAM-1). However, the mechanism underlying the selective binding of different ligands by alpha4beta7 remains obscure. In this study, we demonstrate that CCL25 and CXCL10 induce distinct active conformers of alpha4beta7 with a high affinity for either MAdCAM 1 or VCAM-1. Single-cell force measurements show that CCL25 increases the affinity of alpha4beta7 for MAdCAM-1 but decreases its affinity for VCAM-1, whereas CXCL10 has the opposite effect. Structurally, CCL25 induces a more extended active conformation of alpha4beta7 compared with CXCL10-activated integrin. These two distinct intermediate open alpha4beta7 conformers selectively bind to MAdCAM-1 or VCAM-1 by distinguishing their immunoglobulin domain 2. Notably, Mn2+ fully opens alpha4beta7 with a high affinity for both ligands. Thus, integrin alpha4beta7 adopts different active conformations to switch its ligand-binding specificity. PMID- 29789441 TI - Metformin counteracts the effects of FSH on rat Sertoli cell proliferation. AB - Metformin (MET) is one of the most widely used anti-hyperglycemic agents for treating patients with type 2 diabetes and it has started to be used in pediatric population at ages when Sertoli cells are still proliferating. It is well known that follicle-stimulating hormone (FSH) is the major Sertoli cell mitogen. The aim of the study is to investigate a possible effect of MET, which has been shown to have anti-proliferative properties, on FSH regulation of postnatal Sertoli cell proliferation and on the molecular mechanisms involved in this regulation. The present study was performed in eight-day-old rat Sertoli cell cultures. The results obtained show that MET in the presence of FSH increases phosphorylated acetyl-CoA carboxylase and decreases phosphorylated p70S6K levels. Moreover, we show that MET decreases FSH-stimulated Sertoli cell proliferation, and this decrease is accompanied by a reduction in FSH-stimulated Ccnd1 and Ccnd2 expression and an increase in cell cycle inhibitor p21Cip expression. Altogether, these results suggest that MET can, at least in part, counteract the effect of FSH on postnatal Sertoli cell proliferation. PMID- 29789442 TI - Ovine prenatal growth restriction impacts glucose metabolism and body composition throughout life in both sexes. AB - Low birthweight is a risk factor for later adverse health. Here the impact of placentally mediated prenatal growth restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth restricted pregnancies respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks). Dual-energy X-ray absorptiometry revealed lower bone mineral density in restricted vs normal lambs at 11, 41, 64 and 107 weeks, with males > females from 41 weeks onwards. Body fat percentage was higher in females vs males throughout, in restricted vs normal lambs at weaning (both sexes) and in restricted vs normal females at mid-adulthood. Insulin secretion after glucose challenge was greater in restricted vs normal of both sexes at 7 weeks and in restricted males at 32 weeks. In both sexes, fasting glucose concentrations were greater in restricted offspring across the life course, while glucose area under the curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance. Therefore, prenatal growth restriction has negative consequences for body composition and metabolism throughout the life course with the effects modulated by sex differences in postnatal growth rates, fat deposition and bone mass accrual. PMID- 29789444 TI - Short-term Seizure Outcomes in Childhood Epilepsy. AB - BACKGROUND AND OBJECTIVES: Seizure freedom is the optimal response to antiepileptic treatment. In previous studies, it has been shown that between 61% and 71% of children with epilepsy achieve seizure freedom, whereas 7% to 20% have drug-resistant epilepsy. The definition of drug resistance has not been consistent across studies, and there is a lack of contemporary population-based data. We used data from a large nationwide child cohort to provide such information, implementing the current standard definition of drug resistance. METHODS: The study was based on the Norwegian Mother and Child Cohort Study. Potential epilepsy cases were identified through registry linkages and parental questionnaires. Medical record reviews and parental interviews were used to collect clinical information and to classify seizures, epilepsies, and etiologies. RESULTS: The cohort included 112 745 eligible children aged 3 to 13 years (median age 7 years) at end of follow-up. Of these, 600 were epilepsy cases with at least 1 year of follow-up since epilepsy onset (median follow-up time: 5.8 years). There were 178 (30%) who had developed drug-resistant epilepsy, 353 (59%) who had been seizure free for >=1 year, and 69 (12%) with intermediate seizure outcomes. Having an identified cause of epilepsy (genetic, structural, metabolic, or infectious) was associated with unsatisfactory seizure outcome (48% drug resistance) and influenced the relative risk associated with other prognostic factors. Sociodemographic characteristics were not associated with short-term seizure outcomes. CONCLUSIONS: Drug resistance occurs in 3 out of 10 children with epilepsy, whereas 6 out of 10 become seizure free. Having an identified cause of epilepsy is associated with poor response to treatment. PMID- 29789443 TI - Low-intensity pulsed ultrasound stimulation facilitates in vitro osteogenic differentiation of human adipose-derived stem cells via up-regulation of heat shock protein (HSP)70, HSP90, and bone morphogenetic protein (BMP) signaling pathway. AB - Low-intensity pulsed ultrasound (LIPUS) has positive effects on osteogenic differentiation. However, the effect of LIPUS on osteogenic differentiation of human adipose-derived stem cells (hASCs) is unclear. In the present study, we investigated whether LIPUS could promote the proliferation and osteogenic differentiation of hASCs. hASCs were isolated and osteogenically induced with LIPUS stimulation at 20 and 30 mW cm-2 for 30 min day-1 Cell proliferation and osteogenic differentiation potential of hASCs were respectively analyzed by cell counting kit-8 assay, Alizarin Red S staining, real-time polymerase chain reaction, and Western blotting. The results indicated that LIPUS stimulation did not significantly affect the proliferation of hASCs, but significantly increased their alkaline phosphatase activity on day 6 of culture and markedly promoted the formation of mineralized nodules on day 21 of culture. The mRNA expression levels of runt-related transcription factor, osteopontin, and osteocalcin were significantly up-regulated by LIPUS stimulation. LIPUS stimulation did not affect the expression of heat shock protein (HSP) 27, HSP40, bone morphogenetic protein (BMP)-6 and BMP-9, but significantly up-regulated the protein levels of HSP70, HSP90, BMP-2, and BMP-7 in the hASCs. Further studies found that LIPUS increased the mRNA levels of Smad 1 and Smad 5, elevated the phosphorylation of Smad 1/5, and suppressed the expression of BMP antagonist Noggin. These findings indicated that LIPUS stimulation enhanced osteogenic differentiation of hASCs possibly through the up-regulation of HSP70 and HSP90 expression and activation of BMP signaling pathway. Therefore, LIPUS might have the potential to promote the repair of bone defect. PMID- 29789445 TI - Thermal Effect of a Woolen Cap in Low Birth Weight Infants During Kangaroo Care. AB - BACKGROUND AND OBJECTIVES: World Health Organization guidelines recommend covering the head during kangaroo mother care (KMC), but the effect of a cap on neonatal thermal control during KMC remains to be defined. Our objective was to assess the effectiveness and safety of a woolen cap in maintaining low birth weight infants (LBWIs) in normal thermal range during KMC. METHODS: Three hundred LBWI candidates for KMC in 3 African hospitals were randomly assigned to KMC with (CAP group) or without (NOCAP group) a woolen cap in a 1:1 ratio during the first week after birth. Axillary temperature was measured every 6 hours. Maternal and room temperature and adherence to skin-to-skin contact were registered at the same time points. RESULTS: A total number of 5064 measurements were recorded (median 19 measurements per subject; interquartile range: 10-25). Mean time spent in normal temperature range was 55% (SD 24) in CAP and 56% (SD 24) in NOCAP groups. Multivariable analysis estimated a rate ratio of 0.92 (95% confidence interval: 0.84 to 1.00; P = .06) for the effect of the cap versus no cap on time spent in the normal temperature range. CONCLUSIONS: In these 3 African, low resource settings and so many days post birth, the use of a woolen cap was safe but provided no advantages in maintaining LBWI in the normal thermal range while being in a KMC ward. LBWIs spent only half of the time in the normal temperature range despite warm rooms and skin-to-skin contact. Maintaining normothermia in LBWIs remains an unfinished challenge in low-resource settings. PMID- 29789447 TI - Segment-Tube: Spatio-Temporal Action Localization in Untrimmed Videos with Per Frame Segmentation. AB - Inspired by the recent spatio-temporal action localization efforts with tubelets (sequences of bounding boxes), we present a new spatio-temporal action localization detector Segment-tube, which consists of sequences of per-frame segmentation masks. The proposed Segment-tube detector can temporally pinpoint the starting/ending frame of each action category in the presence of preceding/subsequent interference actions in untrimmed videos. Simultaneously, the Segment-tube detector produces per-frame segmentation masks instead of bounding boxes, offering superior spatial accuracy to tubelets. This is achieved by alternating iterative optimization between temporal action localization and spatial action segmentation. Experimental results on three datasets validated the efficacy of the proposed method, including (1) temporal action localization on the THUMOS 2014 dataset; (2) spatial action segmentation on the Segtrack dataset; and (3) joint spatio-temporal action localization on the newly proposed ActSeg dataset. It is shown that our method compares favorably with existing state-of the-art methods. PMID- 29789448 TI - A Nonlinear Calibration Algorithm Based on Harmonic Decomposition for Two-Axis Fluxgate Sensors. AB - Nonlinearity is a prominent limitation to the calibration performance for two axis fluxgate sensors. In this paper, a novel nonlinear calibration algorithm taking into account the nonlinearity of errors is proposed. In order to establish the nonlinear calibration model, the combined effort of all time-invariant errors is analyzed in detail, and then harmonic decomposition method is utilized to estimate the compensation coefficients. Meanwhile, the proposed nonlinear calibration algorithm is validated and compared with a classical calibration algorithm by experiments. The experimental results show that, after the nonlinear calibration, the maximum deviation of magnetic field magnitude is decreased from 1302 nT to 30 nT, which is smaller than 81 nT after the classical calibration. Furthermore, for the two-axis fluxgate sensor used as magnetic compass, the maximum error of heading is corrected from 1.86 degrees to 0.07 degrees , which is approximately 11% in contrast with 0.62 degrees after the classical calibration. The results suggest an effective way to improve the calibration performance of two-axis fluxgate sensors. PMID- 29789446 TI - Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection. AB - Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS) platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP) consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%). The sensitivity for detecting single nucleotide variants (SNVs) and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM), delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation. PMID- 29789449 TI - Automatic Identification of Alpine Mass Movements by a Combination of Seismic and Infrasound Sensors. AB - The automatic detection and identification of alpine mass movements such as debris flows, debris floods, or landslides have been of increasing importance for devising mitigation measures in densely populated and intensively used alpine regions. Since these mass movements emit characteristic seismic and acoustic waves in the low-frequency range (. PMID- 29789450 TI - Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine. AB - The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax(r) FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A-E). This vaccine consists of inactivated dual subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and >=3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV 1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy. PMID- 29789453 TI - In Situ Determination of Bisphenol A in Beverage Using a Molybdenum Selenide/Reduced Graphene Oxide Nanoparticle Composite Modified Glassy Carbon Electrode. AB - Due to the endocrine disturbing effects of bisphenol A (BPA) on organisms, rapid detection has become one of the most important techniques for monitoring its levels in the aqueous solutions associated with plastics and human beings. In this paper, a glassy carbon electrode (GCE) modified with molybdenum selenide/reduced graphene oxide (MoSe2/rGO) was fabricated for in situ determination of bisphenol A in several beverages. The surface area of the electrode dramatically increases due to the existence of ultra-thin nanosheets in a flower-like structure of MoSe2. Adding phosphotungstic acid in the electrolyte can significantly enhance the repeatability (RSD = 0.4%) and reproducibility (RSD = 2.2%) of the electrode. Under the optimized condition (pH = 6.5), the linear range of BPA was from 0.1 MUM-100 MUM and the detection limit was 0.015 MUM (S/N = 3). When using the as-prepared electrode for analyzing BPA in beverage samples without any pretreatments, the recoveries ranged from 98-107%, and the concentrations were from below the detection limit to 1.7 MUM, indicating its potential prospect for routine analysis of BPA. PMID- 29789454 TI - Magnetorelaxometry in the Presence of a DC Bias Field of Ferromagnetic Nanoparticles Bearing a Viscoelastic Corona. AB - With allowance for orientational Brownian motion, the magnetorelaxometry (MRX) signal, i.e., the decay of magnetization generated by an ensemble of ferromagnet nanoparticles, each of which bears a macromolecular corona (a loose layer of polymer gel) is studied. The rheology of corona is modelled by the Jeffreys scheme. The latter, although comprising only three phenomenological parameters, enables one to describe a wide spectrum of viscoelastic media: from linearly viscous liquids to weakly-fluent gels. The "transverse" configuration of MRX is considered where the system is subjected to a DC (constant bias) field, whereas the probing field is applied perpendicularly to the bias one. The analysis shows that the rate of magnetization decay strongly depends on the state of corona and slows down with enhancement of the corona elasticity. In addition, for the case of "transverse" MRX, we consider the integral time, i.e., the characteristic that is applicable to relaxation processes with an arbitrary number of decay modes. Expressions for the dependence of the integral time on the corona elasticity parameter and temperature are derived. PMID- 29789451 TI - Zebrafish Models of Rare Hereditary Pediatric Diseases. AB - Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even when the mapping results are unambiguous, the affected gene might be of unknown function. In these cases, understanding how a particular genotype can result in a phenotype also needs carefully designed experimental work. Model organism genetics can offer a straightforward experimental setup for hypothesis testing. Containing orthologs for over 80% of the genes involved in human diseases, zebrafish (Danio rerio) has emerged as one of the top disease models over the past decade. A plethora of genetic tools makes it easy to create mutations in almost any gene of the zebrafish genome and these mutant strains can be used in high-throughput preclinical screens for active molecules. As this small vertebrate species offers several other advantages as well, its popularity in biomedical research is bound to increase, with "aquarium to bedside" drug development pipelines taking a more prevalent role in the near future. PMID- 29789455 TI - Map Changes and Theme Evolution in Work Hours: A Co-Word Analysis. AB - (1) Background: Work hours are the basic carrier impacting employees' work-life experience and organizational performance, and employees have greater anxiety in relation to work hours as new technology requires an increasingly faster work rhythm. However, scientific research on this topic lags far behind the practice, calling to attention the need for research on work hours from the perspective of historical evolution; (2) Methods: The Bibliometric method is used to analyze the 6364 articles and their contained 77 high-frequency keywords related to work hours from the Web of Science published between 1901 and 2017. Additionally, an individual-organization-society integrative perspective was adopted to describe the map changes and theme evolution of work hours; (3) Results and conclusions: The hot spots of research at the organizational level changed significantly around 1990, with the theme of "long work hours" becoming the core issue in recent years. Studies on the individual level have gradually moved from physiological aspects to the issues of burnout and psychological distress. Research topics related to the social level are somewhat loose, and mainly focused on work-life conflict areas. In addition, the cluster analysis based on the high-frequency keywords classifies six research types according to their research themes. Based on these findings, future trends are proposed to provide theoretical and practical reference for future studies. PMID- 29789456 TI - Human Health Risk Assessment of Toxic Elements in Farmland Topsoil with Source Identification in Jilin Province, China. AB - The presence of toxic elements in agricultural soils from anthropogenic activities is a potential threat to human health through the food chain. In this study, the concentration of toxic elements in 122 agricultural topsoil composite samples were determined in order to study the current status, identify their sources and assess the level of pollution and human health risk. The results showed that the mean concentrations of Zn, Cu, Pb, Cd, Hg and As in the farmland topsoil were 21.72, 15.09, 36.08, 0.2451, 0.0378 and 4.957 mg.kg-1, respectively. The spatial distribution showed that the soils were mainly contaminated by Cd, Pb and Hg in midwest Jilin but by Cu and As in the east. According to the pollution index (Pi), Nemerow integrated pollution index (PN) and Geo-Accumulation Index (Igeo), Cd and Pb were the main pollutants in the soils. The occurrence of these elements was caused by anthropogenic activities and they were concentrated in the Songyuan-Changchun-Siping economic belt. There is limited non-carcinogenic and carcinogenic health risk to humans. Principal component analyses suggest the Pb, Cd and Hg soil contamination was mainly derived from anthropogenic activities in the Midwest, but all examined toxic elements in the east were mainly due to geogenic anomalies and came from atmospheric deposition. PMID- 29789458 TI - Flying Real-Time Network to Coordinate Disaster Relief Activities in Urban Areas ?. AB - While there have been important advances within wireless communication technology, the provision of communication support during disaster relief activities remains an open issue. The literature in disaster research reports several major restrictions to conducting first response activities in urban areas, given the limitations of telephone networks and radio systems to provide digital communication in the field. In search-and-rescue operations, the communication requirements are increased, since the first responders need to rely on real-time and reliable communication to perform their activities and coordinate their efforts with other teams. Therefore, these limitations open the door to improvisation during disaster relief efforts. In this paper, we argue that flying ad-hoc networks can provide the communication support needed in these scenarios, and propose a new solution towards that goal. The proposal involves the use of flying witness units, implemented using drones, that act as communication gateways between first responders working at different locations of the affected area. The proposal is named the Flying Real-Time Network, and its feasibility to provide communication in a disaster scenario is shown by presenting both a real-time schedulability analysis of message delivery, as well as simulations of the communication support in a physical scenario inspired by a real incident. The obtained results were highly positive and consistent, therefore this proposal represents a step forward towards the solution of this open issue. PMID- 29789452 TI - Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort. AB - Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions. PMID- 29789457 TI - Enhanced Catalytic Reduction of 4-Nitrophenol Driven by Fe3O4-Au Magnetic Nanocomposite Interface Engineering: From Facile Preparation to Recyclable Application. AB - In this work, we report the enhanced catalytic reduction of 4-nitrophenol driven by Fe3O4-Au magnetic nanocomposite interface engineering. A facile solvothermal method is employed for Fe3O4 hollow microspheres and Fe3O4-Au magnetic nanocomposite synthesis via a seed deposition process. Complementary structural, chemical composition and valence state studies validate that the as-obtained samples are formed in a pure magnetite phase. A series of characterizations including conventional scanning/transmission electron microscopy (SEM/TEM), Mossbauer spectroscopy, magnetic testing and elemental mapping is conducted to unveil the structural and physical characteristics of the developed Fe3O4-Au magnetic nanocomposites. By adjusting the quantity of Au seeds coating on the polyethyleneimine-dithiocarbamates (PEI-DTC)-modified surfaces of Fe3O4 hollow microspheres, the correlation between the amount of Au seeds and the catalytic ability of Fe3O4-Au magnetic nanocomposites for 4-nitrophenol (4-NP) is investigated systematically. Importantly, bearing remarkable recyclable features, our developed Fe3O4-Au magnetic nanocomposites can be readily separated with a magnet. Such Fe3O4-Au magnetic nanocomposites shine the light on highly efficient catalysts for 4-NP reduction at the mass production level. PMID- 29789459 TI - The Influence of Shape on the Output Potential of ZnO Nanostructures: Sensitivity to Parallel versus Perpendicular Forces. AB - With the consistent shrinking of devices, micro-systems are, nowadays, widely used in areas such as biomedics, electronics, automobiles, and measurement devices. As devices shrunk, so too did their energy consumptions, opening the way for the use of nanogenerators (NGs) as power sources. In particular, to harvest energy from an object's motion (mechanical vibrations, torsional forces, or pressure), present NGs are mainly composed of piezoelectric materials in which, upon an applied compressive or strain force, an electrical field is produced that can be used to power a device. The focus of this work is to simulate the piezoelectric effect in different ZnO nanostructures to optimize the output potential generated by a nanodevice. In these simulations, cylindrical nanowires, nanomushrooms, and nanotrees were created, and the influence of the nanostructures' shape on the output potential was studied as a function of applied parallel and perpendicular forces. The obtained results demonstrated that the output potential is linearly proportional to the applied force and that perpendicular forces are more efficient in all structures. However, nanotrees were found to have an increased sensitivity to parallel applied forces, which resulted in a large enhancement of the output efficiency. These results could then open a new path to increase the efficiency of piezoelectric nanogenerators. PMID- 29789461 TI - Co-Morbidities as Predictors of Airflow Limitation among Smokers in England. AB - The prevalence of co-morbidities among patients with Chronic Obstructive Pulmonary Disease (COPD) is well documented in the literature. Therefore, this pilot study aimed to identify whether co-morbidities screening would enhance COPD case-finding. Smoking patients were approached at Croydon University Hospital and two local community pharmacies (CPs). Their co-morbidities, respiratory symptoms, smoking pack-years and exercise capacity were collected. Airflow limitation was determined using handheld spirometry (COPD-6) device. The prevalence of airflow limitation was 42% (n = 21/50). The main identified predictors of airflow limitation were: co-morbidities (OR = 9, CI: 1.04-77.81, p = 0.025), respiratory symptoms (OR = 33.54, CI: 1.06-11.77, p = 0.039) and smoking history of >=20 pack years (OR = 3.94, CI: 1.13-13.64, p = 0.029). CPs were the main location for case finding. This study demonstrated the need to screen for co-morbidities for COPD case-finding within CPs. PMID- 29789462 TI - Identifying the Driving Factors of Water Quality in a Sub-Watershed of the Republican River Basin, Kansas USA. AB - Studies have shown that the agricultural expansion and land use changes in the Midwest of the U.S. are major drivers for increased nonpoint source pollution throughout the regional river systems. In this study, we empirically examined the relationship of planted area and production of three dominant crops with nitrate flux in the Republican River, Kansas, a sub-watershed of Mississippi River Basin. Our results show that land use in the region could not explain the observed changes in nitrate flux in the river. Instead, after including explanatory variables such as precipitation, growing degree days, and well water irrigation in the regression model we found that irrigation and spring precipitation could explain >85% of the variability in nitrate flux from 2000 to 2014. This suggests that changes in crop acreage and production alone cannot explain variability in nitrate flux. Future agricultural policy for the region should focus on controlling both the timing and amount of fertilizer applied to the field to reduce the potential leaching of excess fertilizer through spring time runoff and/or over-irrigation into nearby river systems. PMID- 29789463 TI - Properties of Ferrite Garnet (Bi, Lu, Y)3(Fe, Ga)5O12 Thin Film Materials Prepared by RF Magnetron Sputtering. AB - This work is devoted to physical vapor deposition synthesis, and characterisation of bismuth and lutetium-substituted ferrite-garnet thin-film materials for magneto-optic (MO) applications. The properties of garnet thin films sputtered using a target of nominal composition type Bi0.9Lu1.85Y0.25Fe4.0Ga1O12 are studied. By measuring the optical transmission spectra at room temperature, the optical constants and the accurate film thicknesses can be evaluated using Swanepoel's envelope method. The refractive index data are found to be matching very closely to these derived from Cauchy's dispersion formula for the entire spectral range between 300 and 2500 nm. The optical absorption coefficient and the extinction coefficient data are studied for both the as-deposited and annealed garnet thin-film samples. A new approach is applied to accurately derive the optical constants data simultaneously with the physical layer thickness, using a combination approach employing custom-built spectrum-fitting software in conjunction with Swanepoel's envelope method. MO properties, such as specific Faraday rotation, MO figure of merit and MO swing factor are also investigated for several annealed garnet-phase films. PMID- 29789460 TI - Frizzled Receptors as Potential Therapeutic Targets in Human Cancers. AB - Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers. PMID- 29789465 TI - Efficacy, Safety, and Usability of Remifentanil as Premedication for INSURE in Preterm Neonates. AB - Background: We previously reported a 67% extubation failure with INSURE (Intubation, Surfactant, Extubation) using morphine as analgosedative premedication. Remifentanil, a rapid- and short-acting narcotic, might be ideal for INSURE, but efficacy and safety data for this indication are limited. Objectives: To assess whether remifentanil premedication increases extubation success rates compared with morphine, and to evaluate remifentanil's safety and usability in a teaching hospital context. Methods: Retrospective review of remifentanil orders for premedication, at a large teaching hospital neonatal intensive care unit (NICU). We compared INSURE failure rates (needing invasive ventilation after INSURE) with prior morphine-associated rates. Additionally, we surveyed NICU staff to identify usability and logistic issues with remifentanil. Results: 73 remifentanil doses were administered to 62 neonates (mean 31.6 +/- 3.8 weeks' gestation). Extubation was successful in 88%, vs. 33% with morphine premedication (p < 0.001). Significant adverse events included chest wall rigidity (4%), one case of cardiopulmonary resuscitation (CPR) post-surfactant, naloxone reversal (5%), and notable transient desaturation (34%). Among 137 completed surveys, 57% indicated concerns, including delayed drug availability (median 1.1 h after order), rapid desaturations narrowing intubation timeframes and hindering trainee involvement, and difficulty with bag-mask ventilation after unsuccessful intubation attempts. Accordingly, 33% of ultimate intubators were attending neonatologists, versus 16% trainees. Conclusions: Remifentanil premedication was superior to morphine in allowing successful extubation, despite occasional chest wall rigidity and unfavorable conditions for trainees. We recommend direct supervision and INSURE protocols aimed at ensuring rapid intubation. PMID- 29789464 TI - Role of mTOR Complexes in Neurogenesis. AB - Dysregulation of neural stem cells (NSCs) is associated with several neurodevelopmental disorders, including epilepsy and autism spectrum disorder. The mammalian target of rapamycin (mTOR) integrates the intracellular signals to control cell growth, nutrient metabolism, and protein translation. mTOR regulates many functions in the development of the brain, such as proliferation, differentiation, migration, and dendrite formation. In addition, mTOR is important in synaptic formation and plasticity. Abnormalities in mTOR activity is linked with severe deficits in nervous system development, including tumors, autism, and seizures. Dissecting the wide-ranging roles of mTOR activity during critical periods in development will greatly expand our understanding of neurogenesis. PMID- 29789468 TI - In Vitro Evaluation of 2D-Printed Edible Films for the Buccal Delivery of Diclofenac Sodium. AB - Printing technologies have recently emerged in the development of novel drug delivery systems toward personalized medicine, to improve the performance of formulations, existing bioavailability patterns, and patients' compliance. In the context of two-dimensional printing, this article presents the development of buccal films that are designed to efficiently deliver a class II compound (diclofenac sodium), according to the Biopharmaceutics Classification System (BCS), to the oral cavity. The preparation of drug-loaded inks was carried out based on solubility studies and evaluation of rheological properties, combining ethanol and propylene glycol as optimal solvents. Deposition of the drug was achieved by increasing the number of printing layers onto edible substrates, to produce formulations with dose variance. Thermal analysis, X-ray diffraction, and infrared spectroscopy were used to characterize the developed films. Drug loading and water uptake studies complemented the initial assessment of the films, and preliminary in vitro studies were conducted to further evaluate their performance. The in vitro release profiles were recorded in simulated saliva, presenting the complete release of the incorporated active in a period of 10 min. The effect of multiple layers on the overall performance of films was completed with in vitro permeation studies, revealing the correlation between the number of printed layers and the apparent permeability coefficient. PMID- 29789466 TI - Association of Tea Consumption with Risk of Alzheimer's Disease and Anti-Beta Amyloid Effects of Tea. AB - Neurodegenerative disease Alzheimer's disease (AD) is attracting growing concern because of an increasing patient population among the elderly. Tea consumption is considered a natural complementary therapy for neurodegenerative diseases. In this paper, epidemiological studies on the association between tea consumption and the reduced risk of AD are reviewed and the anti-amyloid effects of related bioactivities in tea are summarized. Future challenges regarding the role of tea in preventing AD are also discussed. PMID- 29789467 TI - The Present and Future of Whole Genome Sequencing (WGS) and Whole Metagenome Sequencing (WMS) for Surveillance of Antimicrobial Resistant Microorganisms and Antimicrobial Resistance Genes across the Food Chain. AB - Antimicrobial resistance (AMR) surveillance is a critical step within risk assessment schemes, as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions, and detecting new trends and emerging threats linked to food. Surveillance of AMR is currently based on the isolation of indicator microorganisms and the phenotypic characterization of clinical, environmental and food strains isolated. However, this approach provides very limited information on the mechanisms driving AMR or on the presence or spread of AMR genes throughout the food chain. Whole-genome sequencing (WGS) of bacterial pathogens has shown potential for epidemiological surveillance, outbreak detection, and infection control. In addition, whole metagenome sequencing (WMS) allows for the culture-independent analysis of complex microbial communities, providing useful information on AMR genes occurrence. Both technologies can assist the tracking of AMR genes and mobile genetic elements, providing the necessary information for the implementation of quantitative risk assessments and allowing for the identification of hotspots and routes of transmission of AMR across the food chain. This review article summarizes the information currently available on the use of WGS and WMS for surveillance of AMR in foodborne pathogenic bacteria and food-related samples and discusses future needs that will have to be considered for the routine implementation of these next-generation sequencing methodologies with this aim. In particular, methodological constraints that impede the use at a global scale of these high-throughput sequencing (HTS) technologies are identified, and the standardization of methods and protocols is suggested as a measure to upgrade HTS based AMR surveillance schemes. PMID- 29789470 TI - Physical Activity Recommendations for Health and Beyond in Currently Inactive Populations. AB - Widespread persistent inactivity makes continued efforts in physical activity promotion a persistent challenge. The precise content of physical activity recommendations is not broadly known, and there are concerns that the general messaging of the guidelines, including the recommendations to perform at least 150 min of at least moderate intensity physical activity per week might seem unattainable for and even actually discourage currently inactive people. Here we show that there are a myriad of ways of being physically active, and provide (in part) out-of-the-box examples of evidence based, pragmatic, easily accessible physical activity regimes below 150 min and/or with lower than moderate intensity that yield meaningful health benefits for currently inactive people. PMID- 29789469 TI - Fungal Diversity in Lichens: From Extremotolerance to Interactions with Algae. AB - Lichen symbioses develop long-living thallus structures even in the harshest environments on Earth. These structures are also habitats for many other microscopic organisms, including other fungi, which vary in their specificity and interaction with the whole symbiotic system. This contribution reviews the recent progress regarding the understanding of the lichen-inhabiting fungi that are achieved by multiphasic approaches (culturing, microscopy, and sequencing). The lichen mycobiome comprises a more or less specific pool of species that can develop symptoms on their hosts, a generalist environmental pool, and a pool of transient species. Typically, the fungal classes Dothideomycetes, Eurotiomycetes, Leotiomycetes, Sordariomycetes, and Tremellomycetes predominate the associated fungal communities. While symptomatic lichenicolous fungi belong to lichen forming lineages, many of the other fungi that are found have close relatives that are known from different ecological niches, including both plant and animal pathogens, and rock colonizers. A significant fraction of yet unnamed melanized ('black') fungi belong to the classes Chaethothyriomycetes and Dothideomycetes. These lineages tolerate the stressful conditions and harsh environments that affect their hosts, and therefore are interpreted as extremotolerant fungi. Some of these taxa can also form lichen-like associations with the algae of the lichen system when they are enforced to symbiosis by co-culturing assays. PMID- 29789471 TI - Brownian Motion at Lipid Membranes: A Comparison of Hydrodynamic Models Describing and Experiments Quantifying Diffusion within Lipid Bilayers. AB - The capability of lipid bilayers to exhibit fluid-phase behavior is a fascinating property, which enables, for example, membrane-associated components, such as lipids (domains) and transmembrane proteins, to diffuse within the membrane. These diffusion processes are of paramount importance for cells, as they are for example involved in cell signaling processes or the recycling of membrane components, but also for recently developed analytical approaches, which use differences in the mobility for certain analytical purposes, such as in-membrane purification of membrane proteins or the analysis of multivalent interactions. Here, models describing the Brownian motion of membrane inclusions (lipids, peptides, proteins, and complexes thereof) in model bilayers (giant unilamellar vesicles, black lipid membranes, supported lipid bilayers) are summarized and model predictions are compared with the available experimental data, thereby allowing for evaluating the validity of the introduced models. It will be shown that models describing the diffusion in freestanding (Saffman-Delbruck and Hughes Pailthorpe-White model) and supported bilayers (the Evans-Sackmann model) are well supported by experiments, though only few experimental studies have been published so far for the latter case, calling for additional tests to reach the same level of experimental confirmation that is currently available for the case of freestanding bilayers. PMID- 29789473 TI - Effect of Sewage Irrigation on the CT-Measured Soil Pore Characteristics of a Clay Farmland in Northern China. AB - Sewage irrigation has a strong influence on the physical, chemical, and biological properties of soil. However, the effects of sewage irrigation on the pore characteristics of soil are not well understood. This study compares the effects of sewage irrigation and groundwater irrigation on computed tomography (CT)-measured pore parameters and examines the relationships between CT-measured pore parameters and soil physicochemical and microbial properties. Intact soil cores were collected from S1 irrigated with sewage for 25 years, S2 irrigated with sewage for 52 years, and CK irrigated with groundwater. Various soil pore characteristics were determined, including the total pore number, macropore number (>1 mm diam.), coarse mesopore number (0.264-1 mm diam.), total porosity, macroporosity, coarse mesoporosity, and circularity. The results indicated that sewage irrigation significantly affected soil pore number and porosity. Compared with S1 and S2, CK exhibited a higher average total pore number (91), macropore number (40), coarse mesopore number (51), total porosity (2.08%), macroporosity (1.90%), and coarse mesoporosity (0.18%) throughout the 50-350 mm layer. At depths of 200-350 mm, S2 exhibited the lowest average total pore number (33), macropore number (13), coarse mesopore number (21), total porosity (0.42%), macroporosity (0.35%), and coarse mesoporosity (0.07%) among the three sites. In addition, the average pore numbers and porosity at depths of 200-350 mm decreased with increasing sewage irrigation time. There were significant positive correlations between pore features (including pore numbers and porosity) and soil properties (phosphorus content and fungi numbers). Our results suggest that decreased macropore numbers and macroporosity in the sewage-irrigated farmland may strongly intensify the accumulation of metals and nutrients in the upper layer. The findings of this study are useful for understanding the negative effects of sewage irrigation on soil pore structure and are critical for developing sustainable strategies in agriculture. PMID- 29789472 TI - The Impact of Nutrition and Health Claims on Consumer Perceptions and Portion Size Selection: Results from a Nationally Representative Survey. AB - Nutrition and health claims on foods can help consumers make healthier food choices. However, claims may have a 'halo' effect, influencing consumer perceptions of foods and increasing consumption. Evidence for these effects are typically demonstrated in experiments with small samples, limiting generalisability. The current study aimed to overcome this limitation through the use of a nationally representative survey. In a cross-sectional survey of 1039 adults across the island of Ireland, respondents were presented with three different claims (nutrition claim = "Low in fat"; health claim = "With plant sterols. Proven to lower cholesterol"; satiety claim = "Fuller for longer") on four different foods (cereal, soup, lasagne, and yoghurt). Participants answered questions on perceived healthiness, tastiness, and fillingness of the products with different claims and also selected a portion size they would consume. Claims influenced fillingness perceptions of some of the foods. However, there was little influence of claims on tastiness or healthiness perceptions or the portion size selected. Psychological factors such as consumers' familiarity with foods carrying claims and belief in the claims were the most consistent predictors of perceptions and portion size selection. Future research should identify additional consumer factors that may moderate the relationships between claims, perceptions, and consumption. PMID- 29789475 TI - An Identity-Based Anti-Quantum Privacy-Preserving Blind Authentication in Wireless Sensor Networks. AB - With the development of wireless sensor networks, IoT devices are crucial for the Smart City; these devices change people's lives such as e-payment and e-voting systems. However, in these two systems, the state-of-art authentication protocols based on traditional number theory cannot defeat a quantum computer attack. In order to protect user privacy and guarantee trustworthy of big data, we propose a new identity-based blind signature scheme based on number theorem research unit lattice, this scheme mainly uses a rejection sampling theorem instead of constructing a trapdoor. Meanwhile, this scheme does not depend on complex public key infrastructure and can resist quantum computer attack. Then we design an e payment protocol using the proposed scheme. Furthermore, we prove our scheme is secure in the random oracle, and satisfies confidentiality, integrity, and non repudiation. Finally, we demonstrate that the proposed scheme outperforms the other traditional existing identity-based blind signature schemes in signing speed and verification speed, outperforms the other lattice-based blind signature in signing speed, verification speed, and signing secret key size. PMID- 29789474 TI - Design of a Novel MEMS Microgripper with Rotatory Electrostatic Comb-Drive Actuators for Biomedical Applications. AB - Primary tumors of patients can release circulating tumor cells (CTCs) to flow inside of their blood. The CTCs have different mechanical properties in comparison with red and white blood cells, and their detection may be employed to study the efficiency of medical treatments against cancer. We present the design of a novel MEMS microgripper with rotatory electrostatic comb-drive actuators for mechanical properties characterization of cells. The microgripper has a compact structural configuration of four polysilicon layers and a simple performance that control the opening and closing displacements of the microgripper tips. The microgripper has a mobile arm, a fixed arm, two different actuators and two serpentine springs, which are designed based on the SUMMiT V surface micromachining process from Sandia National Laboratories. The proposed microgripper operates at its first rotational resonant frequency and its mobile arm has a controlled displacement of 40 um at both opening and closing directions using dc and ac bias voltages. Analytical models are developed to predict the stiffness, damping forces and first torsional resonant frequency of the microgripper. In addition, finite element method (FEM) models are obtained to estimate the mechanical behavior of the microgripper. The results of the analytical models agree very well respect to FEM simulations. The microgripper has a first rotational resonant frequency of 463.8 Hz without gripped cell and it can operate up to with maximum dc and ac voltages of 23.4 V and 129.2 V, respectively. Based on the results of the analytical and FEM models about the performance of the proposed microgripper, it could be used as a dispositive for mechanical properties characterization of circulating tumor cells (CTCs). PMID- 29789476 TI - Female Facial Attractiveness Assessed from Three-Dimensional Contour Lines by University Students. AB - BACKGROUND: Three-dimensional (3D) images could provide more accurate evaluation for facial attractiveness than two-dimensional (2D) images. The 3D facial image could be simplified into gray scale 3D contour lines. Whether female facial attractiveness could be perceived in these simplified 3D facial contour lines should be determined. METHODS: A series of 100 2D photographs (one frontal and two lateral views) and 3D contour lines extracted from 3D facial images of females were projected onto a screen. Each image presentation lasted 5 s, and the evaluators marked their impression of each image's facial attractiveness on a five-point Likert scale within 3 s of its presentation. The evaluation of the 3D contour lines was performed twice, 2 weeks apart. The evaluators were university students. RESULTS: High consistency (r = 0.92) was found for the first and second evaluation of 3D facial contour lines for female facial attractiveness. The judgments of unattractive face were more consistent than the judgments of attractive face. Male students tended to give lower scores than female students in the evaluation of female facial attractiveness. CONCLUSIONS: Female facial attractiveness could be evaluated by 3D facial contour lines. 3D facial contour lines should be one of the key factors of facial attractiveness. PMID- 29789478 TI - Strategies to Improve Activity Recognition Based on Skeletal Tracking: Applying Restrictions Regarding Body Parts and Similarity Boundaries. AB - This paper aims to improve activity recognition systems based on skeletal tracking through the study of two different strategies (and its combination): (a) specialized body parts analysis and (b) stricter restrictions for the most easily detectable activities. The study was performed using the Extended Body-Angles Algorithm, which is able to analyze activities using only a single key sample. This system allows to select, for each considered activity, which are its relevant joints, which makes it possible to monitor the body of the user selecting only a subset of the same. But this feature of the system has both advantages and disadvantages. As a consequence, in the past we had some difficulties with the recognition of activities that only have a small subset of the joints of the body as relevant. The goal of this work, therefore, is to analyze the effect produced by the application of several strategies on the results of an activity recognition system based on skeletal tracking joint oriented devices. Strategies that we applied with the purpose of improve the recognition rates of the activities with a small subset of relevant joints. Through the results of this work, we aim to give the scientific community some first indications about which considered strategy is better. PMID- 29789477 TI - MS/MS-Guided Isolation of Clarinoside, a New Anti-Inflammatory Pentalogin Derivative. AB - Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem mass spectrometry (MS) and quantum mechanics (QM) calculations, the tridimensional structure was unravelled after isolation and NMR analysis. The absolute configuration was assigned by comparison of experimental and theoretical synchrotron radiation circular dichroism spectra. Both compounds were tested for anti-inflammatory activity, and compound 1 showed the ability to inhibit the production of interleukin-8 (Il-8) with an IC 50 value of 9.17 MU M. PMID- 29789479 TI - Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter. AB - Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies. PMID- 29789482 TI - The Social Basis of Vaccine Questioning and Refusal: A Qualitative Study Employing Bourdieu's Concepts of 'Capitals' and 'Habitus'. AB - This article is an in-depth analysis of the social nature of vaccine decision making. It employs the sociological theory of Bourdieu and Ingram to consider how parents experience non-vaccination as a valued form of capital in specific communities, and how this can affect their decision-making. Drawing on research conducted in two Australian cities, our qualitative analysis of new interview data shows that parents experience disjuncture and tugs towards 'appropriate' forms of vaccination behavior in their social networks, as these link to broader behaviors around food, school choices and birth practices. We show how differences emerge between the two cities based on study designs, such that we are able to see some parents at the center of groups valorizing their decisions, whilst others feel marginalized within their communities for their decisions to vaccinate. We draw on the work of philosopher Mark Navin to consider how all parents join epistemic communities that reward compliance and conformity with the status quo and consider what this means for interventions that seek to influence the flow of pro-vaccine information through vaccine-critical social groups. PMID- 29789483 TI - Removal of Crystal Violet by Using Reduced-Graphene-Oxide-Supported Bimetallic Fe/Ni Nanoparticles (rGO/Fe/Ni): Application of Artificial Intelligence Modeling for the Optimization Process. AB - Reduced-graphene-oxide-supported bimetallic Fe/Ni nanoparticles were synthesized in this study for the removal of crystal violet (CV) dye from aqueous solutions. This material was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS), Raman spectroscopy, N2-sorption, and X-ray photoelectron spectroscopy (XPS). The influence of independent parameters (namely, initial dye concentration, initial pH, contact time, and temperature) on the removal efficiency were investigated via Box-Behnken design (BBD). Artificial intelligence (i.e., artificial neural network, genetic algorithm, and particle swarm optimization) was used to optimize and predict the optimum conditions and obtain the maximum removal efficiency. The zero point of charge (pHZPC) of rGO/Fe/Ni composites was determined by using the salt addition method. The experimental equilibrium data were fitted well to the Freundlich model for the evaluation of the actual behavior of CV adsorption, and the maximum adsorption capacity was estimated as 2000.00 mg/g. The kinetic study discloses that the adsorption processes can be satisfactorily described by the pseudo-second-order model. The values of Gibbs free energy change (DeltaG0), entropy change (DeltaS0), and enthalpy change (DeltaH0) demonstrate the spontaneous and endothermic nature of the adsorption of CV onto rGO/Fe/Ni composites. PMID- 29789484 TI - Nursing Intervention Practices for Smoking Cessation: A Large Survey in Hong Kong. AB - Previous studies have shown that nursing interventions are effective in helping people to stop smoking, but that the participation of nurses in tobacco control activities has been far from satisfactory. The primary objective of this study is to identify factors that encourage or discourage nurses from participating in providing smoking-cessation interventions to their clients, based on the 5 A's (ask, advise, assess, assist, arrange) framework. A cross-sectional survey was conducted among 4413 nurses in Hong Kong from different clinical specialties. A logistics regression analysis found that predictors for the practicing of all of the 5 A's are nurses who want to receive training in smoking-cessation interventions, those who have received such training, and those who are primarily working in a medical unit or in ambulatory/outpatient settings. The regression model also showed that attitude towards smoking cessation was positively associated with all of the 5 A's. The results indicate a need to encourage and provide nurses with opportunities to receive training on smoking-cessation interventions. Strategies to persuade nurses to provide smoking-cessation interventions are also important, since nurses are motivated to perform smoking cessation interventions when they feel a stronger sense of mission to control tobacco use. PMID- 29789480 TI - Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer. AB - Iron is an essential element for the growth and proliferation of cells. Cellular iron uptake, storage, utilization and export are tightly regulated to maintain iron homeostasis. However, cellular iron metabolism pathways are disturbed in most cancer cells. To maintain rapid growth and proliferation, cancer cells acquire large amounts of iron by altering expression of iron metabolism- related proteins. In this paper, normal cellular iron metabolism and the alterations of iron metabolic pathways in cancer cells were summarized. Therapeutic strategies based on targeting the altered iron metabolism were also discussed and disrupting redox homeostasis by intracellular high levels of iron provides new insight for cancer therapy. Altered iron metabolism constitutes a promising therapeutic target for cancer therapy. PMID- 29789487 TI - Transmitting Pulse Encoding for Beyond-PRT Retransmitting Deception Jamming Detection in Spaceborne Synthetic Aperture Radar (SAR). AB - Retransmitting deception jamming (RDJ) degrades and misleads the Synthetic Aperture Radar (SAR) image interpretation by forming false targets. The beyond Pulse Repetition Time (PRT) RDJ enlarges the effective jamming area without constraining the jammer location to reduce the spaceborne SAR working effectiveness. In order to detect the beyond-PRT RDJ and enhance the working efficiency in electronic countermeasure environment, the transmitting pulse encoding method for use in spaceborne SAR is proposed based on the geometry and signal models of beyond-PRT RDJ. Optimum binary codes with maximum number of detection windows are determined by the encoding procedure. The detected area is found to be proportional to the code length and the encoding efficiencies of even and odd codes are analyzed. The simulation results validate the effectiveness of the transmitting pulse encoding method for beyond-PRT RDJ detection in spaceborne SAR. PMID- 29789485 TI - Association of Plasma Lipids and Polar Metabolites with Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study. AB - The diagnosis of osteoporosis is mainly based on clinical examination and bone mineral density assessments. The present pilot study compares the plasma lipid and polar metabolite profiles in blood plasma of 95 Singaporean-Chinese (SC) menopausal women with normal and low bone mineral density (BMD) using an untargeted metabolomic approach. The primary finding of this study was the association between lipids and femoral neck BMD in SC menopausal women. Twelve lipids were identified to be associated with low BMD by the orthogonal partial least squares (OPLS) model. Plasma concentrations of eight glycerophospholipid, glycerolipid, and sphingolipid species were significantly lower in menopausal women with low BMD but higher in two glycerophospholipid species (phosphatidylinositol and phosphatidic acid). Further, this study found no significant differences in plasma amino acid metabolites. However, trends for lower 4-aminobutyric acid, turanose, proline, aminopropionitrile, threonine, and methionine were found in women with low BMD. This pilot study identified associations between lipid metabolism and femoral neck BMD in SC women. Further studies are required on larger populations for evaluating the bone health effect of these compounds and their usefulness as clinical biomarkers for osteoporosis prediction in women. PMID- 29789486 TI - Prevalence and Risk Factors for Hepatitis B Virus Infection in Roma and Non-Roma People in Slovakia. AB - : Prevalence of Hepatitis B is relatively low in developed European countries. However specific subpopulations may exist within each country with markedly different Hepatitis B burden. Roma minority is very numerous in Slovakia and their lifestyle is completely different to non-Roma population. The aim of this study is to map Hepatitis B prevalence in Roma and compare it to non-Roma population and to explore potential socio-economic and health related risk factors. Cross-sectional epidemiology study was performed in Slovakia that included randomly sampled Roma population and geographically corresponding random sampled non-Roma population. Comprehensive questionnaire about risk factors was administered and blood samples were drawn for Hepatitis B serology and virology tests. Altogether 855 participants were included. Global Hepatitis B surface Antigen (HBsAg) positivity rate was 7.7% (i.e., active Hepatitis B) and anti Hepatitis B core IgG antibody (antiHBcIgG) positivity rate was 34.6%. Roma population had significantly higher prevalence of Hepatitis B, both active chronic infection (12.4%; 95% Confidence Interval (CI) 9.58%-15.97% versus 2.8%; 95% CI 1.56%-4.91%; p < 0.0001) and antiHBcIgG positivity (52.8%; 95% CI 48.17% 57.44% versus 25.9%; 95% CI 12.56%-20.02%; p < 0.0001) Main risk factors for HBsAg positivity were Roma ethnicity, male sex and tattoo. CONCLUSION: There is a very high prevalence of Hepatitis B in Roma communities in Slovakia, with potential for grave medical consequences. PMID- 29789481 TI - Concepts and Methods to Access Novel Antibiotics from Actinomycetes. AB - Actinomycetes have been proven to be an excellent source of secondary metabolites for more than half a century. Exhibiting various bioactivities, they provide valuable approved drugs in clinical use. Most microorganisms are still untapped in terms of their capacity to produce secondary metabolites, since only a small fraction can be cultured in the laboratory. Thus, improving cultivation techniques to extend the range of secondary metabolite producers accessible under laboratory conditions is an important first step in prospecting underexplored sources for the isolation of novel antibiotics. Currently uncultured actinobacteria can be made available by bioprospecting extreme or simply habitats other than soil. Furthermore, bioinformatic analysis of genomes reveals most producers to harbour many more biosynthetic gene clusters than compounds identified from any single strain, which translates into a silent biosynthetic potential of the microbial world for the production of yet unknown natural products. This review covers discovery strategies and innovative methods recently employed to access the untapped reservoir of natural products. The focus is the order of actinomycetes although most approaches are similarly applicable to other microbes. Advanced cultivation methods, genomics- and metagenomics-based approaches, as well as modern metabolomics-inspired methods are highlighted to emphasise the interplay of different disciplines to improve access to novel natural products. PMID- 29789488 TI - Superhydrophobic Natural and Artificial Surfaces-A Structural Approach. AB - Since ancient times humans observed animal and plants features and tried to adapt them according to their own needs. Biomimetics represents the foundation of many inventions from various fields: From transportation devices (helicopter, airplane, submarine) and flying techniques, to sports' wear industry (swimming suits, scuba diving gear, Velcro closure system), bullet proof vests made from Kevlar etc. It is true that nature provides numerous noteworthy models (shark skin, spider web, lotus leaves), referring both to the plant and animal kingdom. This review paper summarizes a few of "nature's interventions" in human evolution, regarding understanding of surface wettability and development of innovative special surfaces. Empirical models are described in order to reveal the science behind special wettable surfaces (superhydrophobic /superhydrophilic). Materials and methods used in order to artificially obtain special wettable surfaces are described in correlation with plants' and animals' unique features. Emphasis is placed on joining superhydrophobic and superhydrophilic surfaces, with important applications in cell culturing, microorganism isolation/separation and molecule screening techniques. Bio inspired wettability is presented as a constitutive part of traditional devices/systems, intended to improve their characteristics and extend performances. PMID- 29789489 TI - Reconciling the Entomological Hazard and Disease Risk in the Lyme Disease System. AB - Lyme disease (LD) is a commonly cited model for the link between habitat loss and/or fragmentation and disease emergence, based in part on studies showing that forest patch size is negatively related to LD entomological risk. An equivalent relationship has not, however, been shown between patch size and LD incidence (LDI). Because entomological risk is measured at the patch scale, while LDI is generally assessed in relation to aggregate landscape statistics such as forest cover, we posit that the contribution of individual patches to human LD risk has not yet been directly evaluated. We design a model that directly links theoretical entomological risk at the patch scale to larger-scale epidemiological data. We evaluate its predictions for relative LD risk in artificial landscapes with varying composition and configuration, and test its ability to predict countywide LDI in a 12-county region of New York. On simulated landscapes, we find that the model predicts a unimodal relationship between LD incidence and forest cover, mean patch size, and mean minimum distance (a measure of isolation), and a protective effect for percolation probability (a measure of connectivity). In New York, risk indices generated by this model are significantly related to countywide LDI. The results suggest that the lack of concordance between entomological risk and LDI may be partially resolved by this style of model. PMID- 29789490 TI - Evaluation of Lactic Acid Bacteria on the Inhibition of Vibrio parahaemolyticus Infection and Its Application to Food Systems. AB - This study tested the effect of lactic acid bacteria (LAB) inhibition on Vibrio parahaemolyticus BCRC (Bioresource Collection and Research Center) 10806 and BCRC 12865 in a food model. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays indicated that Caco-2 cells were not damaged after a two-hour treatment with lactic acid bacteria (LAB) and V. parahaemolyticus. The LAB cell culture and supernatant effectively inhibited the growth of V. parahaemolyticus in a food model. ELISA (Enzyme-linked immunosorbent assay) results indicated the significant inhibition of TNF-alpha; IL-1beta; and IL-6; but Lactobacillus plantarum PM 222 and L. plantarum LP 735 did not significantly affect IL-8 levels. Real-time polymerase chain reaction (PCR) results indicated that LAB could inhibit the mRNA expression of proinflammatory cytokines IL-8; IL-6; and TNF-alpha; which were induced by V. parahaemolyticus. After rat-received LAB; the expression levels of TNF-alpha; IL-6; and IL-8 in the serum decreased significantly. In intestinal histology; the rat that received L. plantarum PM 222 and L. plantarum LP 010 was able to alleviate the intestinal villi damage caused by V. parahaemolyticus; which also helped reduce cell apoptosis. In conclusion; our results indicate that LAB can inhibit inflammatory responses caused by V. parahaemolyticus and can effectively inhibit the growth of V. parahaemolyticus in food products. PMID- 29789492 TI - A Continuum Model for the Effect of Dynamic Recrystallization on the Stress Strain Response. AB - Austenitic Stainless Steels and High-Strength Low-Alloy (HSLA) steels show significant dynamic recovery and dynamic recrystallization (DRX) during hot forming. In order to design optimal and safe hot-formed products, a good understanding and constitutive description of the material behavior is vital. A new continuum model is presented and validated on a wide range of deformation conditions including high strain rate deformation. The model is presented in rate form to allow for the prediction of material behavior in transient process conditions. The proposed model is capable of accurately describing the stress strain behavior of AISI 316LN in hot forming conditions, also the high strain rate DRX-induced softening observed during hot torsion of HSLA is accurately predicted. It is shown that the increase in recrystallization rate at high strain rates observed in experiments can be captured by including the elastic energy due to the dynamic stress in the driving pressure for recrystallization. Furthermore, the predicted resulting grain sizes follow the power-law dependence with steady state stress that is often reported in literature and the evolution during hot deformation shows the expected trend. PMID- 29789491 TI - From Evidence-Based Research to Practice-Based Evidence: Disseminating a Web Based Computer-Tailored Workplace Sitting Intervention through a Health Promotion Organisation. AB - Prolonged sitting has been linked to adverse health outcomes; therefore, we developed and examined a web-based, computer-tailored workplace sitting intervention. As we had previously shown good effectiveness, the next stage was to conduct a dissemination study. This study reports on the dissemination efforts of a health promotion organisation, associated costs, reach achieved, and attributes of the website users. The organisation systematically registered all the time and resources invested to promote the intervention. Website usage statistics (reach) and descriptive statistics (website users' attributes) were also assessed. Online strategies (promotion on their homepage; sending e-mails, newsletters, Twitter, Facebook and LinkedIn posts to professional partners) were the main dissemination methods. The total time investment was 25.6 h, which cost approximately 845 EUR in salaries. After sixteen months, 1599 adults had visited the website and 1500 (93.8%) completed the survey to receive personalized sitting advice. This sample was 38.3 +/- 11.0 years, mainly female (76.9%), college/university educated (89.0%), highly sedentary (88.5% sat >8 h/day) and intending to change (93.0%) their sitting. Given the small time and money investment, these outcomes are positive and indicate the potential for wide-scale dissemination. However, more efforts are needed to reach men, non college/university educated employees, and those not intending behavioural change. PMID- 29789493 TI - Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients. AB - The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD. PMID- 29789494 TI - Evaluating the Intoxicating Degree of Liquor Products with Combinations of Fusel Alcohols, Acids, and Esters. AB - To investigate the effects of fusel alcohols on the intoxicating degree of liquor products, formulated liquors (FLs) were prepared by blending 1-propanol, isobutanol, and isoamyl alcohol with ethanol, organic acids, and corresponding ethyl esters to simulate the formula of traditional Chinese liquors. The prepared FLs were submitted for evaluation of their intoxicating degree (ID). The results showed that the fusel alcohols had a biphasic effect on the IDs of the FLs, depending on the comprehensive coordination of the characteristic minor components. The importance of the suitable ratio of alcohols/acids/esters (RAAE) on the IDs was also revealed. Under an optimal ratio level, the fusel alcohols exhibited negligible effects on the IDs of the FLs. Moreover, the ratio of isoamyl alcohol to isobutanol (IA/IB) showed a strong positive correlation to the IDs of the FLs. This study lays a foundation for the potential application in producing low-ID liquor. PMID- 29789495 TI - Apolipoprotein E and Atherosclerosis: From Lipoprotein Metabolism to MicroRNA Control of Inflammation. AB - Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipoprotein clearance in the liver and protect against macrophage foam cell formation, our recent understanding of the influence that apoE can exert to control atherosclerosis has significantly widened. Among apoE's newfound athero-protective properties include an ability to control exaggerated hematopoiesis, blood monocyte activation and aortic stiffening in mice with hyperlipidemia. Mechanisms responsible for these exciting new properties extend beyond apoE's ability to prevent cellular lipid excess. Rather, new findings have revealed a role for apoE in regulating microRNA controlled cellular signaling in cells of the immune system and vascular wall. Remarkably, infusions of apoE-responsive microRNA mimics were shown to substitute for apoE in protecting against systemic and vascular inflammation to suppress atherosclerosis in mice with hyperlipidemia. Finally, more recent evidence suggests that apoE may control the release of microvesicles that could modulate cellular signaling, inflammation and atherosclerosis at a distance. These exciting new findings position apoE within the emerging field of intercellular communication that could introduce new approaches to control atherosclerosis cardiovascular disease. PMID- 29789496 TI - Determinants of Inappropriate Admissions in County Hospitals in Rural China: A Cross-Sectional Study. AB - Inappropriate admissions have contributed to the rapid increase in hospitalisations in rural China. This study characterised the degree and determinants of inappropriate admissions in county hospitals. We used expert consultation to develop an appropriateness evaluation protocol that included nine requirements for services and 21 indicators of disease severity. A total of 2230 medical records from 2014 were collected from five county hospitals by stratified cluster sampling and evaluated for appropriateness using the protocol in 2016. The determinants of inappropriate admissions were analysed by two-level logistic regression. The overall inappropriate admission rate was 15.2%. Patients aged. PMID- 29789497 TI - Treating p53 Mutant Aggregation-Associated Cancer. AB - p53 is a tumor suppressor protein. Under stressful conditions, p53 tightly regulates cell growth by promoting apoptosis and DNA repair. When p53 becomes mutated, it loses its function, resulting in abnormal cell proliferation and tumor progression. Depending on the p53 mutation, it has been shown to form aggregates leading to negative gain of function of the protein. p53 mutant associated aggregation has been observed in several cancer tissues and has been shown to promote tumor growth. Recent studies show correlation between p53 mutant aggregation, functional loss, and tumor growth. Moreover, p53 aggregation has been observed in biopsies, patient tissues, and in vivo studies. Given the fact that over fifty percent of cancers have p53 mutation and several of them are prone to aggregation, therapeutic strategies are needed for treating p53 mutant aggregation associated cancers. Recent studies using polyarginine analogues and designer peptides for inhibiting p53 aggregation and tumor growth gives further encouragement in treating cancer as a protein aggregation disease. In this review, we highlight the recent efforts in targeting p53 aggregation in cancer and propose the use of small stress molecules as potential p53-antiaggregation drugs. PMID- 29789499 TI - Human Mercury Exposure in Yanomami Indigenous Villages from the Brazilian Amazon. AB - In the Brazilian Amazon, where the majority of Yanomami villages are settled, mercury (Hg) exposure due to artisanal small-scale gold mining (ASGM) has been reported since the 1980s. This study assessed mercury exposure in the Yanomami reserve and whether the level of contamination was related to the ASGM geographical location. It was conducted using a cross-sectional study of 19 villages. Direct interviews were performed and hair samples were used as a bioindicator of Hg exposure. The Prevalence-Ratio (PR) was estimated as an indicator of association between ASGM geographical locations and human exposure to mercury. Mercury levels (239 hair samples) ranged between 0.4 and 22.1 MUg.g-1 and presented substantial differences amongst the villages. In the Waikas-Aracaca region, where current ASGM was reported, we observed the highest Hg concentrations (median = 15.5 MUg.g-1). Almost all participants presented with hair-Hg levels >6 MUg.g-1 (prevalence = 92.3%). In the Paapiu region, we observed the lowest concentrations (median = 3.2 MUg.g-1; prevalence = 6.7%). Our findings showed that the Waikas Ye'kuana and Waikas Aracaca villages presented with 4.4 (PR = 4.4; Confidence Interval (CI) 95% = 2.2-9.0) and 14.0 (PR = 14.0; CI 95% = 7.9-24.9) times higher prevalence of hair-Hg concentration, respectively, compared with Paapiu. Considering seasonal variation of Hg-exposure, the lowest concentrations were observed during the wet season (June-September) and the highest in the dry season (December-April). Our study suggests that there is an association between mercury exposure and ASGM geographical locations. PMID- 29789498 TI - Tools for Detection of Schistosomiasis in Resource Limited Settings. AB - Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention from governments and stakeholders in healthcare. One of the critical areas that is hugely under developed is the development of accurate diagnostics for both intestinal and urogenital schistosomiasis. Diagnosis of schistosomiasis is important for the detection and treatment of disease in endemic and non-endemic settings. A conclusive detection method is also an indispensable part of treatment, both in the clinic and during mass drug administration (MDA), for the monitoring efficacy of treatment. Here, we review the available diagnostic methods and discuss the challenges encountered in diagnosis in resource limited settings. We also present the available diagnostics and cost implications for deployment in resource limited settings. Lastly, we emphasize the need for more funding directed towards the development of affordable diagnostic tools that is affordable for endemic countries as we work towards the elimination of the disease. PMID- 29789500 TI - Human Metapneumovirus Small Hydrophobic Protein Inhibits Interferon Induction in Plasmacytoid Dendritic Cells. AB - Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, encodes a small hydrophobic (SH) protein of unknown function. Here we show that infection of plasmacytoid dendritic cells (pDCs) with a recombinant virus lacking SH expression (rhMPV-DeltaSH) enhanced the secretion of type I interferons (IFNs), which required TLR7 and MyD88 expression. HMPV SH protein inhibited TLR7/MyD88/TRAF6 signaling leading to IFN gene transcription, identifying a novel mechanism by which paramyxovirus SH proteins modulate innate immune responses. PMID- 29789501 TI - Differentiation Between Organic and Non-Organic Apples Using Diffraction Grating and Image Processing-A Cost-Effective Approach. AB - As the expectation for higher quality of life increases, consumers have higher demands for quality food. Food authentication is the technical means of ensuring food is what it says it is. A popular approach to food authentication is based on spectroscopy, which has been widely used for identifying and quantifying the chemical components of an object. This approach is non-destructive and effective but expensive. This paper presents a computer vision-based sensor system for food authentication, i.e., differentiating organic from non-organic apples. This sensor system consists of low-cost hardware and pattern recognition software. We use a flashlight to illuminate apples and capture their images through a diffraction grating. These diffraction images are then converted into a data matrix for classification by pattern recognition algorithms, including k-nearest neighbors (k-NN), support vector machine (SVM) and three partial least squares discriminant analysis (PLS-DA)- based methods. We carry out experiments on a reasonable collection of apple samples and employ a proper pre-processing, resulting in a highest classification accuracy of 94%. Our studies conclude that this sensor system has the potential to provide a viable solution to empower consumers in food authentication. PMID- 29789503 TI - Fully Ab-Initio Determination of the Thermoelectric Properties of Half-Heusler NiTiSn: Crucial Role of Interstitial Ni Defects. AB - For thermoelectric applications, ab initio methods generally fail to predict the transport properties of the materials because of their inability to predict properly the carrier concentrations that control the electronic properties. In this work, a methodology to fill in this gap is applied on the NiTiSn half Heusler phase. For that, we show that the main defects act as donor of electrons and are responsible of the electronic properties of the material. Indeed, the presence of Nii interstitial defects explains the experimental valence band spectrum and its associated band gap reported in the literature. Moreover, combining the DOS of the solid solutions with the determination of the energy of formation of charged defects, we show that Nii defects are also responsible of the measured carrier concentration in experimentally supposed "pure" NiTiSn compounds. Subsequently the thermoelectric properties of NiTiSn can be calculated using a fully ab initio description and an overall correct agreement with experiments is obtained. This methodology can be extended to predict the result of extrinsic doping and thus to select the most efficient dopant for specific thermoelectric applications. PMID- 29789504 TI - The Sound of Words Evokes Affective Brain Responses. AB - The long history of poetry and the arts, as well as recent empirical results suggest that the way a word sounds (e.g., soft vs. harsh) can convey affective information related to emotional responses (e.g., pleasantness vs. harshness). However, the neural correlates of the affective potential of the sound of words remain unknown. In an fMRI study involving passive listening, we focused on the affective dimension of arousal and presented words organized in two discrete groups of sublexical (i.e., sound) arousal (high vs. low), while controlling for lexical (i.e., semantic) arousal. Words sounding high arousing, compared to their low arousing counterparts, resulted in an enhanced BOLD signal in bilateral posterior insula, the right auditory and premotor cortex, and the right supramarginal gyrus. This finding provides first evidence on the neural correlates of affectivity in the sound of words. Given the similarity of this neural network to that of nonverbal emotional expressions and affective prosody, our results support a unifying view that suggests a core neural network underlying any type of affective sound processing. PMID- 29789505 TI - Multilayer Black Phosphorus Near-Infrared Photodetectors. AB - Black phosphorus (BP), owing to its distinguished properties, has become one of the most competitive candidates for photodetectors. However, there has been little attention paid on photo-response performance of multilayer BP nanoflakes with large layer thickness. In fact, multilayer BP nanoflakes with large layer thickness have greater potential from the fabrication viewpoint as well as due to the physical properties than single or few layer ones. In this report, the thickness-dependence of the intrinsic property of BP photodetectors in the dark was initially investigated. Then the photo-response performance (including responsivity, photo-gain, photo-switching time, noise equivalent power, and specific detectivity) of BP photodetectors with relative thicker thickness was explored under a near-infrared laser beam (lambdaIR = 830 nm). Our experimental results reveal the impact of BP's thickness on the current intensity of the channel and show degenerated p-type BP is beneficial for larger current intensity. More importantly, the photo-response of our thicker BP photodetectors exhibited a larger responsivity up to 2.42 A/W than the few-layer ones and a fast response photo-switching speed (response time is ~2.5 ms) comparable to thinner BP nanoflakes was obtained, indicating BP nanoflakes with larger layer thickness are also promising for application for ultra-fast and ultra-high near-infrared photodetectors. PMID- 29789502 TI - Detection of Dystrophin Dp71 in Human Skeletal Muscle Using an Automated Capillary Western Assay System. AB - BACKGROUND: Dystrophin Dp71 is one of the isoforms produced by the DMD gene which is mutated in patients with Duchenne muscular dystrophy (DMD). Although Dp71 is expressed ubiquitously, it has not been detected in normal skeletal muscle. This study was performed to assess the expression of Dp71 in human skeletal muscle. METHODS: Human skeletal muscle RNA and tissues were obtained commercially. Mouse skeletal muscle was obtained from normal and DMDmdx mice. Dp71 mRNA and protein were determined by reverse-transcription PCR and an automated capillary Western assay system, the Simple Western, respectively. Dp71 was over-expressed or suppressed using a plasmid expressing Dp71 or antisense oligonucleotide, respectively. RESULTS: Full-length Dp71 cDNA was PCR amplified as a single product from human skeletal muscle RNA. A ca. 70 kDa protein peak detected by the Simple Western was determined as Dp71 by over-expressing Dp71 in HEK293 cells, or suppressing Dp71 expression with antisense oligonucleotide in rhabdomyosarcoma cells. The Simple Western assay detected Dp71 in the skeletal muscles of both normal and DMD mice. In human skeletal muscle, Dp71 was also detected. The ratio of Dp71 to vinculin of human skeletal muscle samples varied widely, indicating various levels of Dp71 expression. CONCLUSIONS: Dp71 protein was detected in human skeletal muscle using a highly sensitive capillary Western blotting system. PMID- 29789506 TI - Design and Efficacy of Nanogels Formulations for Intranasal Administration. AB - Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration. PMID- 29789509 TI - Wave Propagation in Aluminum Honeycomb Plate and Debonding Detection Using Scanning Laser Vibrometer. AB - Both the aerospace and marine industry have widely relied on a honeycomb sandwich structure (HSS) because of its high strength-to-weight ratio. However, the intrinsic nature of an adhesively bonded multi-layer structure increases the risk of debonding when the structure is under strain or exposed to varying temperatures. Such defects are normally concealed under the surface but can significantly compromise the strength and stiffness of a structure. In this paper, the guided wave method is used to detect debondings which are located between the skin and the honeycomb in sandwich plates. The propagation of guided waves in honeycomb plates is investigated via numerical techniques, with emphasis placed on demonstrating the behavior of structure-based wave interactions (SWIs). The SWI technique is effective to distinguish heterogeneous structures from homogeneous structures. The excitation frequency is necessary to generate obvious SWIs in HSSs; accordingly, a novel strategy is proposed to select the optimal excitation frequencies. A series of experiments are conducted, the results of which show that the presented procedure can be used to effectively detect the locations and the sizes of single- and multi-damage zones in HSSs. PMID- 29789507 TI - Acute Caffeinated Coffee Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study. AB - INTRODUCTION: Studies evaluating caffeinated coffee (CAF) can reveal ergogenic effects; however, studies on the effects of caffeinated coffee on running are scarce and controversial. AIM: To investigate the effects of CAF consumption compared to decaffeinated coffee (DEC) consumption on time trial performances in an 800-m run in overnight-fasting runners. METHODS: A randomly counterbalanced, double-blind, crossover, placebo-controlled study was conducted with 12 healthy adult males with experience in amateur endurance running. Participants conducted two trials on two different occasions, one day with either CAF or DEC, with a one week washout. After arriving at the data collection site, participants consumed the soluble CAF (5.5 mg/kg of caffeine) or DEC and after 60 min the run was started. Before and after the 800-m race, blood pressure and lactate and glucose concentrations were measured. At the end of the run, the ratings of perceived exertion (RPE) scale was applied. RESULTS: The runners were light consumers of habitual caffeine, with an average ingestion of 91.3 mg (range 6-420 mg/day). Time trial performances did not change between trials (DEF: 2.38 + 0.10 vs. CAF: 2.39 + 0.09 min, p = 0.336), nor did the RPE (DEC: 16.5 + 2.68 vs. CAF: 17.0 + 2.66, p = 0.326). No difference between the trials was observed for glucose and lactate concentrations, or for systolic and diastolic blood pressure levels. CONCLUSION: CAF consumption failed to enhance the time trial performance of an 800-m run in overnight-fasting runners, when compared with DEC ingestion. In addition, no change was found in RPE, blood pressure levels, or blood glucose and lactate concentrations between the two trials. PMID- 29789510 TI - Functioning Mediastinal Paraganglioma Associated with a Germline Mutation of von Hippel-Lindau Gene. AB - We report the case of a 21-year old woman presenting with high blood pressure and raised normetanephrine levels. Indium-111-pentetreotide single photon-emission computed tomography with computed tomography (SPECT/CT) and 2-deoxy-2-[fluorine 18]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showing isolated tracer-uptake by a 2 cm tumor close to the costovertebral angle of the third thoracic vertebra. Thoracic surgery led to normalization of normetanephrine levels. Histological findings were consistent with the presence of a paraganglioma. Mutations in SDHA, SDHB, SDHC, SDHD, RET, SDHAF2, TMEM127, MAX, NF1, FH, MDH2, and EPAS1 were absent, but a heterozygous missense mutation, c.311G > T, was found in exon 1 of the von Hippel-Lindau gene, VHL, resulting in a glycine to valine substitution in the VHL protein at position 104, p.Gly104Val. This same mutation was found in both the mother and the 17-year old sister in whom a small retinal hemangioblastoma was also found. We diagnose an unusual functional mediastinal paraganglioma in this young patient with a germline VHL gene mutation, a mutation previously described as inducing polycythemia and/or pheochromocytoma but not paraganglioma or retinal hemangioblastoma. PMID- 29789508 TI - Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in AMPK-Dependent and Independent Manners. AB - Metformin has been reported to have body weight lowering effects while treating type 2 diabetes. However, limited studies examined the effects of metformin on adipogenesis in vitro, and available data are inconclusive and contradictory. In this study, we examined the effects of a variety of concentrations of metformin on adipocyte differentiation of 3T3-L1 preadipocytes and found metformin exhibits a dual effect on adipogenesis. Metformin at lower concentrations (1.25-2.5 mM) significantly induced adipogenesis while at higher concentrations (5-10 mM) metformin significantly inhibited adipogenesis in 3T3-L1 cells. The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels. Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5' monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt. Pretreatment with compound C, a specific AMPK inhibitor, significantly countered high concentration of metformin-induced inhibition of adipogenesis. Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. PMID- 29789511 TI - The Place of Social Recovery in Mental Health and Related Services. AB - This article looks at the place of social recovery in mental health and social care services, alongside personal recovery. Despite its conceptual and practice centrality to the new meaning of recovery, social recovery has remained a relatively neglected dimension. This article attempts to provide an updated critical commentary based on findings from fifty nine studies, including a variety of research methodologies and methods. Definitions of social recovery within the new meaning of recovery are looked at. This is followed by outlining the development and significance of this dimension as reflected in the key areas of shared decision making, co-production and active citizenship, re-entering employment after experiencing mental ill health, being in employment, poverty and coping with poverty, the economic and the scientific cases for social recovery. The article highlights the connections between service users' experiencing mental health and social care systems, and the implications of ideologies and policies reflecting positions on social recovery. The complexity of social recovery is indicated in each of these areas; the related conceptual and methodological frameworks developed to research this dimension, and key achievements and barriers concerning everyday practice application of social recovery. The summary indicates potential future development perspectives of this dimension. PMID- 29789512 TI - Extreme Ultraviolet to Visible Dispersed Single Photon Detection for Highly Sensitive Sensing of Fundamental Processes in Diverse Samples. AB - The detection of a single photon is the most sensitive method for sensing of photon emission. A common technique for single photon detection uses microchannel plate arrays combined with photocathodes and position sensitive anodes. Here, we report on the combination of such detectors with grating diffraction spectrometers, constituting a low-noise wavelength resolving photon spectroscopy apparatus with versatile applicability. We recapitulate the operation principle of such detectors and present the details of the experimental set-up, which we use to investigate fundamental mechanisms in atomic and molecular systems after excitation with tuneable synchrotron radiation. Extensions for time and polarization resolved measurements are described and examples of recent applications in current research are given. PMID- 29789513 TI - Substructural Connectivity Fingerprint and Extreme Entropy Machines-A New Method of Compound Representation and Analysis. AB - Key-based substructural fingerprints are an important element of computer-aided drug design techniques. The usefulness of the fingerprints in filtering compound databases is invaluable, as they allow for the quick rejection of molecules with a low probability of being active. However, this method is flawed, as it does not consider the connections between substructures. After changing the connections between particular chemical moieties, the fingerprint representation of the compound remains the same, which leads to difficulties in distinguishing between active and inactive compounds. In this study, we present a new method of compound representation-substructural connectivity fingerprints (SCFP), providing information not only about the presence of particular substructures in the molecule but also additional data on substructure connections. Such representation was analyzed by the recently developed methodology-extreme entropy machines (EEM). The SCFP can be a valuable addition to virtual screening tools, as it represents compound structure with greater detail and more specificity, allowing for more accurate classification. PMID- 29789514 TI - Electron-Beam-Lithographed Nanostructures as Reference Materials for Label-Free Scattered-Light Biosensing of Single Filoviruses. AB - Optical biosensors based on scattered-light measurements are being developed for rapid and label-free detection of single virions captured from body fluids. Highly controlled, stable, and non-biohazardous reference materials producing virus-like signals are valuable tools to calibrate, evaluate, and refine the performance of these new optical biosensing methods. To date, spherical polymer nanoparticles have been the only non-biological reference materials employed with scattered-light biosensing techniques. However, pathogens like filoviruses, including the Ebola virus, are far from spherical and their shape strongly affects scattered-light signals. Using electron beam lithography, we fabricated nanostructures resembling individual filamentous virions attached to a biosensing substrate (silicon wafer overlaid with silicon oxide film) and characterized their dimensions with scanning electron and atomic force microscopes. To assess the relevance of these nanostructures, we compared their signals across the visible spectrum to signals recorded from Ebola virus-like particles which exhibit characteristic filamentous morphology. We demonstrate the highly stable nature of our nanostructures and use them to obtain new insights into the relationship between virion dimensions and scattered-light signal. PMID- 29789515 TI - A General Cross-Layer Cloud Scheduling Framework for Multiple IoT Computer Tasks. AB - The diversity of IoT services and applications brings enormous challenges to improving the performance of multiple computer tasks' scheduling in cross-layer cloud computing systems. Unfortunately, the commonly-employed frameworks fail to adapt to the new patterns on the cross-layer cloud. To solve this issue, we design a new computer task scheduling framework for multiple IoT services in cross-layer cloud computing systems. Specifically, we first analyze the features of the cross-layer cloud and computer tasks. Then, we design the scheduling framework based on the analysis and present detailed models to illustrate the procedures of using the framework. With the proposed framework, the IoT services deployed in cross-layer cloud computing systems can dynamically select suitable algorithms and use resources more effectively to finish computer tasks with different objectives. Finally, the algorithms are given based on the framework, and extensive experiments are also given to validate its effectiveness, as well as its superiority. PMID- 29789516 TI - Phytochemical Profile of Brown Rice and Its Nutrigenomic Implications. AB - Whole grain foods have been promoted to be included as one of the important components of a healthy diet because of the relationship between the regular consumption of whole-grain foods and reduced risk of chronic diseases. Rice is a staple food, which has been widely consumed for centuries by many Asian countries. Studies have suggested that brown rice is associated with a wide spectrum of nutrigenomic implications such as anti-diabetic, anti-cholesterol, cardioprotective and antioxidant. This is because of the presence of various phytochemicals that are mainly located in bran layers of brown rice. Therefore, this paper is a review of publications that focuses on the bioactive compounds and nutrigenomic implications of brown rice. Although current evidence supports the fact that the consumption of brown rice is beneficial for health, these studies are heterogeneous in terms of their brown rice samples used and population groups, which cause the evaluation to be difficult. Future clinical studies should focus on the screening of individual bioactive compounds in brown rice with reference to their nutrigenomic implications. PMID- 29789517 TI - Fluorescent Proteins for Investigating Biological Events in Acidic Environments. AB - The interior lumen of acidic organelles (e.g., endosomes, secretory granules, lysosomes and plant vacuoles) is an important platform for modification, transport and degradation of biomolecules as well as signal transduction, which remains challenging to investigate using conventional fluorescent proteins (FPs). Due to the highly acidic luminal environment (pH ~ 4.5-6.0), most FPs and related sensors are apt to lose their fluorescence. To address the need to image in acidic environments, several research groups have developed acid-tolerant FPs in a wide color range. Furthermore, the engineering of pH insensitive sensors, and their concomitant use with pH sensitive sensors for the purpose of pH-calibration has enabled characterization of the role of luminal ions. In this short review, we summarize the recent development of acid-tolerant FPs and related functional sensors and discuss the future prospects for this field. PMID- 29789518 TI - Olive Oil and Soybean Oil Based Intravenous Lipid Emulsions, Liver Biochemistry and Clinical Outcomes. AB - Intravenous lipid emulsions are an essential component of parenteral nutrition (PN). Omega-6 reducing strategies may improve outcomes, including reduced PN associated liver disease, however evidence to support this recommendation is insufficient. The primary objective was to compare serum alkaline phosphatase (ALP), among patients provided with either soybean oil (Intralipid) or predominantly olive oil (Clinoleic) lipid emulsions. In this quasi-experimental study, we reviewed the medical records of surgical and medical adult patients who received lipid emulsions for at least seven consecutive days. Among the 206 patients (110-Intralipid, 96-Clinoleic) there was no significant difference in ALP and remaining liver function tests within 2 weeks of PN therapy initiation between groups, even after control for lipid doses. Macronutrient dosing was similar. Triglyceride level was higher by 0.7 mmol/L in the Clinoleic group; confidence interval 0.21 to 1.1; p = 0.004. The 30-day mortality, length of hospital stay, and proportion of patients admitted to intensive care were not significantly different. The Clinoleic group had a higher infection rate (36% vs. 22%, p = 0.031) and longer intensive care stays (p = 0.045). Well-designed randomized clinical trials comparing these lipid emulsions are necessary to confirm Intralipid superiority over Clinoleic in relation to infections and serum triglycerides. PMID- 29789519 TI - A Macaca Fascicularis Knee Osteoarthritis Model Developed by Modified Hulth Combined with Joint Scratches. AB - BACKGROUND Osteoarthritis is a common degenerative disease of joints, and animal models have important significance in the investigation of this disease. The aim of this study was to develop a better method for developing osteoarthritis models in primates by comparing the modified Hulth score combined with joint scratches modeling method with others. MATERIAL AND METHODS We randomly divided 15 young male Macaca fascicularis and 3 old male Macaca fascicularis into 6 groups (n=3). Knee osteoarthritis (KOA) models were developed with different methods: modified Hulth combined with joint scratches (Group A), modified Hulth (Group B), Hulth (Group C), spontaneous models (Group D); sham-operated (Group E), and blank control (Group F). Morphology and pathology of knee joints were observed at the 8th week after surgery. The levels of WBC, IL-1b, and TGF-b1 in synovial fluid were detected by ELISA. The levels of COL-II, ACAN, and MMP-13 in articular cartilage were examined by RT-qPCR and Western blot. RESULTS In Brittberg and modified Mankin score, Group A was higher than B (P<0.05) and lower than C (P<0.05), and there was no statistically significant difference between Group A and D (P>0.05). Except for Group E and F, the differences were statistically significant among others in WBC, IL-1beta, and TGF-beta1 (P<0.05). COL-II and ACAN decreased and MMP-13 increased, and there was no significant difference between Groups A and D (P>0.05) or between Groups E and F (P>0.05). There were statistically significant differences among other groups (P<0.05). CONCLUSIONS The models developed by modified Hulth combined with joint scratches were the closet to spontaneous models at the 8th week after surgery. PMID- 29789520 TI - T1-Weighted Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Distinguish Between Concurrent Cholesterol Granuloma and Invasive Ductal Carcinoma of the Breast: A Case Report. AB - BACKGROUND Cholesterol granuloma is a benign condition that can be misdiagnosed as breast cancer on mammographic and ultrasound imaging. A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast was imaged with ultrasound elastography and magnetic resonance imaging (MRI) methods, including T1-weighted dynamic contrast-enhanced MRI (DCE-MRI), before biopsy and histopathology. CASE REPORT A 52-year-old woman, with a previous history of intraduct papillomas in both breasts, underwent six-monthly follow-up breast imaging. The most recent breast mammogram showed a progressively enlarging oval mass in the upper inner quadrant (UIQ) of the left breast, and an adjacent irregular mass with microcalcifications. Virtual Touch IQ (VTIQ) shear wave elastography was used with ultrasound of the breast lesions. T1-weighted fat saturation (T1WFS) MRI, T2-weighted short-tau inversion recovery (STIR) MRI, and T1-weighted DCE-MRI were used to image the left breast. T1-weighted DCE-MRI showed that the oval lesion had a high T1-weighted signal and mild progressive enhancement, with a Type I (benign) time-signal intensity curve; the second, irregular, mass showed rapid, intense enhancement with a washout pattern or Type III (malignant) time-signal intensity curve. Histopathology confirmed that the oval mass was a cholesterol granuloma, and the irregular mass was an invasive ductal carcinoma. CONCLUSIONS A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast, showed that ultrasound with shear wave elastography and T1-weighted DCE-MRI could distinguish between cholesterol granuloma and invasive ductal carcinoma. PMID- 29789521 TI - Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis. AB - Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses. PMID- 29789523 TI - Focal brain lesions induced with ultraviolet irradiation. AB - Lesion and inactivation methods have played important roles in neuroscience studies. However, traditional techniques for creating a brain lesion are highly invasive, and control of lesion size and shape using these techniques is not easy. Here, we developed a novel method for creating a lesion on the cortical surface via 365 nm ultraviolet (UV) irradiation without breaking the dura mater. We demonstrated that 2.0 mWh UV irradiation, but not the same amount of non-UV light irradiation, induced an inverted bell-shaped lesion with neuronal loss and accumulation of glial cells. Moreover, the volume of the UV irradiation-induced lesion depended on the UV light exposure amount. We further succeeded in visualizing the lesioned site in a living animal using magnetic resonance imaging (MRI). Importantly, we also observed using an optical imaging technique that the spread of neural activation evoked by adjacent cortical stimulation disappeared only at the UV-irradiated site. In summary, UV irradiation can induce a focal brain lesion with a stable shape and size in a less invasive manner than traditional lesioning methods. This method is applicable to not only neuroscientific lesion experiments but also studies of the focal brain injury recovery process. PMID- 29789524 TI - Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3beta pathway in human lung cancer cells. AB - Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti cancer activity. However, the molecular mechanism by which hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (?psim), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3beta is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K/Akt signaling pathway plays a critical role in hirsutine-mediated GSK3beta dephosphorylation and mitochondrial apoptosis. Our in vivo study also showed that hirsutine effectively inhibits tumor growth in a A549 xenograft mouse model through ROCK1/PTEN/PI3K/Akt signaling-mediated GSK3beta dephosphorylation and apoptosis. Collectively, these findings suggest a hierarchical model in which induction of apoptosis by hirsutine stems primarily from activation of ROCK1 and PTEN, inactivation of PI3K/Akt, leading in turn to GSK3beta dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis. These findings could provide a novel mechanistic basis for the application of hirsutine in the treatment of human lung cancer. PMID- 29789522 TI - A20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation. AB - Microglia, the mononuclear phagocytes of the central nervous system (CNS), are important for the maintenance of CNS homeostasis, but also critically contribute to CNS pathology. Here we demonstrate that the nuclear factor kappa B (NF-kappaB) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology. In mice, deletion of A20 in microglia increases microglial cell number and affects microglial regulation of neuronal synaptic function. Administration of a sublethal dose of lipopolysaccharide induces massive microglia activation, neuroinflammation, and lethality in mice with microglia-confined A20 deficiency. Microglia A20 deficiency also exacerbates multiple sclerosis (MS)-like disease, due to hyperactivation of the Nlrp3 inflammasome leading to enhanced interleukin-1beta secretion and CNS inflammation. Finally, we confirm a Nlrp3 inflammasome signature and IL-1beta expression in brain and cerebrospinal fluid from MS patients. Collectively, these data reveal a critical role for A20 in the control of microglia activation and neuroinflammation. PMID- 29789525 TI - Fertilization shapes a well-organized community of bacterial decomposers for accelerated paddy straw degradation. AB - Straw, mainly dry stalks of crops, is an agricultural byproduct. Its incorporation to soils via microbial redistribution is an environment-friendly way to increase fertility. Fertilization influences soil microorganisms and straw degradation. However, our up to date knowledge on the responses of the straw decomposers to fertilization remains elusive. To this end, inoculated with paddy soils with 26-year applications of chemical fertilizers, organic amendments or controls without fertilization, microcosms were anoxically incubated with 13C labelled rice straw amendment. DNA-based stable isotope probing and molecular ecological network analysis were conducted to unravel how straw degrading bacterial species shift in responses to fertilizations, as well as evaluate what their roles/links in the microbiome are. It was found that only a small percentage of the community ecotypes was participating into straw degradation under both fertilizations. Fertilization, especially with organic amendments decreased the predominance of Firmicutes- and Acidobacteria-like straw decomposers but increased those of the copiotrophs, such as beta-Proteobacteria and Bacteroidetes due to increased soil fertility. For the same reason, fertilization shifted the hub species towards those of high degrading potential and created a more stable and efficient microbial consortium. These findings indicate that fertilization shapes a well-organized community of decomposers for accelerated straw degradation. PMID- 29789526 TI - Hox and Wnt pattern the primary body axis of an anthozoan cnidarian before gastrulation. AB - Hox gene transcription factors are important regulators of positional identity along the anterior-posterior axis in bilaterian animals. Cnidarians (e.g., sea anemones, corals, and hydroids) are the sister group to the Bilateria and possess genes related to both anterior and central/posterior class Hox genes. Here we report a previously unrecognized domain of Hox expression in the starlet sea anemone, Nematostella vectensis, beginning at early blastula stages. We explore the relationship of two opposing Hox genes (NvAx6/NvAx1) expressed on each side of the blastula during early development. Functional perturbation reveals that NvAx6 and NvAx1 not only regulate their respective expression domains, but also interact with Wnt genes to pattern the entire oral-aboral axis. These findings suggest an ancient link between Hox/Wnt patterning during axis formation and indicate that oral-aboral domains are likely established during blastula formation in anthozoan cnidarians. PMID- 29789527 TI - Regulator of chromatin condensation 1 abrogates the G1 cell cycle checkpoint via Cdk1 in human papillomavirus E7-expressing epithelium and cervical cancer cells. AB - Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase and plays key roles in nucleo-cytoplasmic transport, mitosis, and nuclear envelope assembly. RCC1 is known to be a critical cell cycle regulator whose loss causes G1 phase arrest, but the molecular basis for this regulation is poorly understood. Furthermore, little is known about the relationship between RCC1 and carcinomas. Human papillomavirus (HPV) infection is highly associated with the development of cervical cancer. The expression and function of RCC1 in HPV-related cervical cancer and cell cycle regulation have not yet been explored. In this study, we first observed that RCC1 immunostaining was mildly increased in cervical cancer tissues and significantly upregulated in HPV E7-expressing cells; this localization was primarily nuclear. We showed that the transcription factor c-Jun transcriptionally upregulates RCC1 via a direct interaction with the RCC1 promoter. Moreover, siRNA-mediated knockdown of RCC1 inhibited G1/S cell cycle progression and DNA synthesis, while overexpression of RCC1 abrogated the G1 checkpoint. RCC1 knockdown downregulated the protein levels of the transcription factor E2F1, especially nuclear E2F1, by promoting its degradation in HPV E7-expressing cells. Overexpression of E2F1 rescued RCC1 knockdown-mediated inhibition of G1/S progression. Additionally, we showed that cyclin-dependent kinase 1 (Cdk1), a known target of E2F1, is involved in G1 checkpoint regulation, as Cdk1 knockdown hindered G1/S progression, while Cdk1 overexpression rescued RCC1 knockdown-mediated effect on G1 cell cycle progression. Furthermore, RCC1 knockdown reduced HPV E7 protein levels, which may in turn downregulate E2F1. Our study explores the function of RCC1 in G1/S cell cycle progression and suggests that RCC1 may be involved in HPV E7-mediated genomic instability. PMID- 29789528 TI - YAP-dependent ubiquitination and degradation of beta-catenin mediates inhibition of Wnt signalling induced by Physalin F in colorectal cancer. AB - Aberrant activation of Wnt/beta-catenin signalling is critical in the progression of human cancers, especially colorectal cancer (CRC). Therefore, inhibition of Wnt/beta-catenin signalling is a significant potential target for CRC therapy. Here, we identified for the first time that Physalin F (PF), a steroid derivative isolated from Physalis angulate, acts as an antagonist of Wnt/beta-catenin signalling. In vitro, PF decreased Wnt3a-induced TOPFlash reporter activity in HEK293T cells and promoted the formation of the beta-catenin destruction complex. Importantly, PF also inhibited Wnt/beta-catenin signalling and accelerated the degradation of beta-catenin in CRC cells. However, PF did not affect the stabilization of Axin or the interaction of beta-catenin with E-cadherin. Interestingly, we further found that PF promoted YAP binding to the beta-catenin destruction complex, which facilitated the ubiquitination and degradation of beta catenin. Silencing and pharmacological inhibition of YAP reversed the formation of the beta-catenin destruction complex induced by PF, implying that YAP binding to the beta-catenin destruction complex was responsible for PF-mediated inhibition of Wnt/beta-catenin signalling. Furthermore, PF observably inhibited tumour growth by down-regulating beta-catenin in tumour-bearing mice. Collectively, our findings indicated that PF inhibited Wnt/beta-catenin signalling by accelerating the ubiquitination and degradation of beta-catenin in a YAP-dependent manner and therefore PF could be a novel potential candidate for CRC therapy. PMID- 29789529 TI - Inhibiting p38 MAPK alpha rescues axonal retrograde transport defects in a mouse model of ALS. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically in the SOD1G93A mouse model of ALS, and have been proposed to play a role in motor neuron degeneration as well as in other pathologies of the nervous system, such as Alzheimer's disease and hereditary neuropathies. In this study, we screen a library of small-molecule kinase inhibitors towards the identification of pharmacological enhancers of the axonal retrograde transport of signalling endosomes, which might be used to normalise the rate of this process in diseased neurons. Inhibitors of p38 mitogen activated protein kinases (p38 MAPK) were identified in this screen and were found to correct deficits in axonal retrograde transport of signalling endosomes in cultured primary SOD1G93A motor neurons. In vitro knockdown experiments revealed that the alpha isoform of p38 MAPK (p38 MAPKalpha) was the sole isoform responsible for SOD1G93A-induced transport deficits. Furthermore, we found that acute treatment with p38 MAPKalpha inhibitors restored the physiological rate of axonal retrograde transport in vivo in early symptomatic SOD1G93A mice. Our findings demonstrate the pathogenic effect of p38 MAPKalpha on axonal retrograde transport and identify a potential therapeutic strategy for ALS. PMID- 29789531 TI - Mitochondrial OXPHOS influences immune cell fate: lessons from hematopoietic AIF deficient and NDUFS4-deficient mouse models. PMID- 29789530 TI - Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping. AB - Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population. PMID- 29789532 TI - Ferroptosis-inducing agents compromise in vitro human islet viability and function. AB - Human islet transplantation has been hampered by donor cell death associated with the islet preparation procedure before transplantation. Regulated necrosis pathways are biochemically and morphologically distinct from apoptosis. Recently, ferroptosis was identified as a non-apoptotic form of iron-dependent regulated necrosis implicated in various pathological conditions. Mediators of islet oxidative stress, including glutathione peroxidase-4 (GPX4), have been identified as inhibitors of ferroptosis, and mechanisms that affect GPX4 function can impact islet function and viability. Ferroptosis has not been investigated directly in human islets, and its relevance in islet transplantation remains unknown. Herein, we sought to determine whether in vitro human islet viability and function is compromised in the presence of two distinct ferroptosis-inducing agents (FIA), erastin or RSL3, and whether these effects could be rescued with ferroptosis inhibitors, ferrostatin-1 (Fer-1), or desferrioxamine (DFO). Viability, as assessed by lactate dehydrogenase (LDH) release, revealed significant death in erastin- and RSL3-treated islets, 20.3% +/- 3.8 and 24.4% +/- 2.5, 24 h post culture, respectively. These effects were ameliorated in islets pre-treated with Fer-1 or the iron chelator, desferrioxamine (DFO). Stimulation index, a marker of islet function revealed a significant reduction in function in erastin-treated islets (control 1.97 +/- 0.13 vs. 50 MUM erastin 1.32 +/- 0.1) (p < 0.05). Fer-1 and DFO pre-treatment alone did not augment islet viability or function. Pre treatment of islets with erastin or Fer-1 did not impact in vivo engraftment in an immunodeficient mouse transplant model. Our data reveal that islets are indeed susceptible to ferroptosis in vitro, and induction of this novel cell death modality leads to compromised islet function, which can be recoverable in the presence of the ferroptosis inhibitors. The in vivo impact of this pathway in islet transplantation remains elusive given the constraints of our study, but warrants continued investigation. PMID- 29789533 TI - SCRaMbLEing to understand and exploit structural variation in genomes. PMID- 29789535 TI - Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. AB - Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ (PAR-binding zinc finger) protein domain to bind PAR with high-affinity. By linking PBZ domains to bimolecular fluorescent complementation biosensors, we developed fluorescent PAR biosensors that allow the detection of temporal and spatial PARylation events in live cells. Exploiting transposon-mediated recombination, we integrate the PAR biosensor en masse into thousands of protein coding genes in living cells. Using these PAR-biosensor "tagged" cells in a genetic screen we carry out a large-scale identification of PARylation targets. This identifies CTIF (CBP80/CBP20-dependent translation initiation factor) as a novel PARylation target of the tankyrase enzymes in the centrosomal region of cells, which plays a role in the distribution of the centrosomal satellites. PMID- 29789534 TI - The novel KLF4/PLAC8 signaling pathway regulates lung cancer growth. AB - Accumulating evidence suggests that placenta-specific 8 (PLAC8) plays an important role in normal cellular process and human diseases, including multiple types of human tumors, and its role is highly relied upon in cellular and physiologic contexts. However, there are no reports on its expression profile and biological roles during lung cancer development. In the current study, both the clinical implications and biological effects of PLAC8 in lung cancer (LC) progression were investigated, and we identified and described the novel Kruppel like factor 4 (KLF4)/PLAC8 regulatory pathway in cancer progression. Elevated PLAC8 levels were positively correlated with tumor size, histological grade, and tumor node metasis (TNM) stage, and LC patients with high PLAC8 expression suffered poor outcomes. In vitro and in vivo assays further revealed that endogenous PLAC8 promoted cell proliferation and tumor formation. We also found downregulated PLAC8 protein in several LC cell lines following the induction of KLF4, and immunohistochemistry analysis of LC tissues by microarray indicated a potential inverse correlation between PLAC8 and KLF4 expression. Luciferase reporter analysis and chromatin immunoprecipitation assays determined that KLF4 negatively regulated PLAC8 promoter activity via directly binding to the promoter region. Furthermore, the growth inhibition resulting from KLF4 overexpression was partially rescued by ectopic PLAC8 expression. Together, our data uncovered a previously unidentified role of PLAC8 as a central mediator in LC progression. PLAC8 was transcriptionally repressed by KLF4, and the novel KLF4/PLAC8 axis may act as a promising candidate target for LC diagnosis and therapy. PMID- 29789536 TI - Long noncoding RNA gastric cancer-related lncRNA1 mediates gastric malignancy through miRNA-885-3p and cyclin-dependent kinase 4. AB - Gastric cancer (GC) is one of the most common malignancy and the third leading cancer-related death in China. Long noncoding RNAs (lncRNAs) have been implicated in numerous tumors, including GC, however, the mechanism of many functional lncRNAs is still unclear. In this study, we identified the abundantly expressed lncRNA, RP11-290F20.3, in GC cells and patient tumor tissues. We named this lncRNA as GC-related lncRNA1 (GCRL1), which could regulate gastric cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, miRNA 885-3p (miR-885-3p) could inhibit the cell proliferation and metastasis in GC by negatively regulating the expression of cyclin-dependent kinase 4 (CDK4) at the post-transcriptional level. Further, GCRL1 promoted the cell proliferation and metastasis by sponging miR-885-3p and hence, positively regulating CDK4 in GC cells. Taken together, our results demonstrate a novel regulatory axis of malignant cell proliferation and invasion in GC, comprising GCRL1, miR-885-3p, and CDK4, which may serve as a potential therapeutic target in GC. PMID- 29789538 TI - Salvianolic acid B inhibits glycolysis in oral squamous cell carcinoma via targeting PI3K/AKT/HIF-1alpha signaling pathway. AB - Our previous study demonstrated a progressive glycolytic perturbation during the course of DMBA-induced hamster oral carcinogenesis, which was attenuated by salvianolic acid B (Sal-B) treatment along with decreased incidences of oral squamous cell carcinoma (OSCC) formation. It was proposed that metabolic modulation should be an additional mode of action attributable to Sal-B's anti carcinogenic activity. However, the molecular mechanisms underlying Sal-B-induced metabolic modulation function remained elusive. In the present study, we performed next-generation sequencing (NGS) profiling in the same animal model and found Sal-B treatment evoked a general downregulation of the phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) and hypoxia inducible factor 1alpha subunit (HIF 1alpha) signaling pathways, which might contribute to Sal-B's metabolic modulation activity. The inhibitory effects of Sal-B on aerobic glycolysis, as well as PI3K/AKT and HIF-1alpha signaling pathways, were validated in two well characterized OSCC cell lines (Cal27 and HN4), and premalignant oral Leuk1 cells and Sal-B treatment led to elevation of the loss of mitochondrial membrane potential (MMP), increased cell apoptosis, and reduced abilities of colony formation. Rescue assays suggested that compared with Sal-B treatment group, Akt or hif-1a overexpression attenuated the inhibitory effect of Sal-B on glucose uptake and intracellular lactate level. Taken together, our results suggested that Sal-B modulated aberrant glucose metabolism via the PI3K/AKT/HIF-1alpha signaling pathways, which might contribute to the anti-carcinogenic activity of Sal-B. PMID- 29789537 TI - Detection of Japanese Encephalitis Virus RNA in Human Throat Samples in Laos - A Pilot study. AB - Japanese encephalitis virus (JEV) is the most commonly identified cause of acute encephalitis syndrome (AES) in Asia. The WHO recommended test is anti-JEV IgM antibody-capture-enzyme-linked-immunosorbent-assay (JEV MAC-ELISA). However, data suggest this has low positive predictive value, with false positives related to other Flavivirus infections and vaccination. JEV RT-PCR in cerebrospinal fluid (CSF) and/or serum is highly specific, but is rarely positive; 0-25% of patients that fulfil the WHO definition of JE (clinical Acute Encephalitis Syndrome (AES) and JEV MAC-ELISA positive). Testing other body fluids by JEV RT-qPCR may improve the diagnosis. As a pilot study thirty patients admitted to Mahosot Hospital 2014 2017, recruited to the South-East-Asia-Encephalitis study, were tested by JEV MAC ELISA and two JEV real-time RT-PCR (RT-qPCR) assays (NS2A and NS3). Eleven (36.7%) were JEV MAC-ELISA positive. Available CSF and serum samples of these patients were JEV RT-qPCR negative but 2 (7%) had JEV RNA detected in their throat swabs. JEV RNA was confirmed by re-testing, and sequencing of RT-qPCR products. As the first apparent report of JEV RNA detection in human throat samples, the provides new perspectives on human JEV infection, potentially informing improving JEV detection. We suggest that testing patients' throat swabs for JEV RNA is performed, in combination with molecular and serological CSF and serum investigations, on a larger scale to investigate the epidemiology of the presence of JEV in human throats. Throat swabs are an easy and non-invasive tool that could be rolled out to a wider population to improve knowledge of JEV molecular epidemiology. PMID- 29789539 TI - Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment. AB - In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes. PMID- 29789540 TI - Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome. AB - Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques. PMID- 29789541 TI - Identifying and characterizing SCRaMbLEd synthetic yeast using ReSCuES. AB - SCRaMbLE is a novel system implemented in the synthetic yeast genome, enabling massive chromosome rearrangements to produce strains with a large genotypic diversity upon induction. Here we describe a reporter of SCRaMbLEd cells using efficient selection, termed ReSCuES, based on a loxP-mediated switch of two auxotrophic markers. We show that all randomly isolated clones contained rearrangements within the synthetic chromosome, demonstrating high efficiency of selection. Using ReSCuES, we illustrate the ability of SCRaMbLE to generate strains with increased tolerance to several stress factors, such as ethanol, heat and acetic acid. Furthermore, by analyzing the tolerant strains, we are able to identify ACE2, a transcription factor required for septum destruction after cytokinesis, as a negative regulator of ethanol tolerance. Collectively, this work not only establishes a generic platform to rapidly identify strains of interest by SCRaMbLE, but also provides methods to dissect the underlying mechanisms of resistance. PMID- 29789543 TI - Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods. AB - Exogenous pathway optimization and chassis engineering are two crucial methods for heterologous pathway expression. The two methods are normally carried out step-wise and in a trial-and-error manner. Here we report a recombinase-based combinatorial method (termed "SCRaMbLE-in") to tackle both challenges simultaneously. SCRaMbLE-in includes an in vitro recombinase toolkit to rapidly prototype and diversify gene expression at the pathway level and an in vivo genome reshuffling system to integrate assembled pathways into the synthetic yeast genome while combinatorially causing massive genome rearrangements in the host chassis. A set of loxP mutant pairs was identified to maximize the efficiency of the in vitro diversification. Exemplar pathways of beta-carotene and violacein were successfully assembled, diversified, and integrated using this SCRaMbLE-in method. High-throughput sequencing was performed on selected engineered strains to reveal the resulting genotype-to-phenotype relationships. The SCRaMbLE-in method proves to be a rapid, efficient, and universal method to fast track the cycle of engineering biology. PMID- 29789542 TI - RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF kappaB-mediated ERK reactivation. AB - Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance. Depletion of RNF25 expression substantially sensitized NSCLC cells to gefitinib treatment, while forced expression of RNF25 augmented gefitinib resistance in sensitive cells. We demonstrated that RNF25 mediates NF-kappaB activation in gefitinib-treated cells, which, in turn, induces reactivation of ERK signal to cause the drug resistance. We identified that the ERK reactivation occurs via the function of cytokines, such as IL-6, whose expression is transcriptionally induced in a gefitinib dependent manner by RNF25-mediated NF-kappaB signals. These results suggest that RNF25 plays an essential role in gefitinib resistance of NSCLC by mediating cross talk between NF-kappaB and ERK pathways, and provide a novel target for the combination therapy to overcome TKI resistance of NSCLC. PMID- 29789544 TI - Development of muscular dystrophy in a CRISPR-engineered mutant rabbit model with frame-disrupting ANO5 mutations. AB - Limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi myopathy type 3 (MMD3) are autosomal recessive muscular dystrophy caused by mutations in the gene encoding anoctamin-5 (ANO5), which belongs to the anoctamin protein family. Two independent lines of mice with complete disruption of ANO5 transcripts did not exhibit overt muscular dystrophy phenotypes; instead, one of these mice was observed to present with some abnormality in sperm motility. In contrast, a third line of ANO5-knockout (KO) mice with residual expression of truncated ANO5 expression was reported to display defective membrane repair and very mild muscle pathology. Many of the ANO5-related patients carry point mutations or small insertions/deletions (indels) in the ANO5 gene. To more closely mimic the human ANO5 mutations, we engineered mutant ANO5 rabbits via co-injection of Cas9 mRNA and sgRNA into the zygotes. CRISPR-mediated small indels in the exon 12 and/or 13 in the mutant rabbits lead to the development of typical signs of muscular dystrophy with increased serum creatine kinase (CK), muscle necrosis, regeneration, fatty replacement and fibrosis. This novel ANO5 mutant rabbit model would be useful in studying the disease pathogenesis and therapeutic treatments for ANO5-deficient muscular dystrophy. PMID- 29789546 TI - A checklist for our community. PMID- 29789547 TI - Empowering peer reviewers with a checklist to improve transparency. AB - Peer review is widely considered fundamental to maintaining the rigour of science, but it often fails to ensure transparency and reduce bias in published papers, and this systematically weakens the quality of published inferences. In part, this is because many reviewers are unaware of important questions to ask with respect to the soundness of the design and analyses, and the presentation of the methods and results; also some reviewers may expect others to be responsible for these tasks. We therefore present a reviewers' checklist of ten questions that address these critical components. Checklists are commonly used by practitioners of other complex tasks, and we see great potential for the wider adoption of checklists for peer review, especially to reduce bias and facilitate transparency in published papers. We expect that such checklists will be well received by many reviewers. PMID- 29789549 TI - Building better yeast. PMID- 29789545 TI - Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism. AB - N6-methyladenosine (m6A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m6A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m6A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs. PMID- 29789548 TI - Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays. AB - Recent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record and manipulate neuronal activity. Combining optical techniques with electrical recordings is of critical importance to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity. However, integration of optical modalities with electrical recordings is challenging due to generation of light-induced artifacts. Here we report a transparent graphene microelectrode technology that eliminates light-induced artifacts to enable crosstalk-free integration of 2 photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. We achieve fabrication of crack- and residue-free graphene electrode surfaces yielding high optical transmittance for 2-photon imaging down to ~ 1 mm below the cortical surface. Transparent graphene microelectrode technology offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations. PMID- 29789550 TI - Neutrophil extracellular traps promote macrophage pyroptosis in sepsis. AB - In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antimicrobial peptides and enzymes, which trap and kill the bacteria extracellularly. In this study, by using a mouse sepsis model, we identified a novel mechanism by which NETs induce macrophage (Mphi) pyroptosis, a caspase-1 dependent regulated cell death. We show that NET-derived HMGB1, acting through RAGE and dynamin-dependent signaling, triggers an intra-Mphi cascade of molecular events including cathepsin B (CatB) release from the ruptured lysosomes, followed by pyroptosome formation and caspase-1 activation, and subsequent Mphi pyroptosis. The study further demonstrates that Mphi pyroptosis augments inflammatory responses following sepsis. These findings shed light on the proinflammatory role of NETs in mediating PMN-Mphi interaction, which therefore influences the progress of inflammation following infection. PMID- 29789551 TI - Epidermal glucocorticoid and mineralocorticoid receptors act cooperatively to regulate epidermal development and counteract skin inflammation. AB - Endogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-kappaB transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation. PMID- 29789552 TI - Similar temperature scale for valence changes in Kondo lattices with different Kondo temperatures. AB - The Kondo model predicts that both the valence at low temperatures and its temperature dependence scale with the characteristic energy TK of the Kondo interaction. Here, we study the evolution of the 4f occupancy with temperature in a series of Yb Kondo lattices using resonant X-ray emission spectroscopy. In agreement with simple theoretical models, we observe a scaling between the valence at low temperature and TK obtained from thermodynamic measurements. In contrast, the temperature scale Tv at which the valence increases with temperature is almost the same in all investigated materials while the Kondo temperatures differ by almost four orders of magnitude. This observation is in remarkable contradiction to both naive expectation and precise theoretical predictions of the Kondo model, asking for further theoretical work in order to explain our findings. Our data exclude the presence of a quantum critical valence transition in YbRh2Si2. PMID- 29789553 TI - Controlling the coherence of a diamond spin qubit through its strain environment. AB - The uncontrolled interaction of a quantum system with its environment is detrimental for quantum coherence. For quantum bits in the solid state, decoherence from thermal vibrations of the surrounding lattice can typically only be suppressed by lowering the temperature of operation. Here, we use a nano electro-mechanical system to mitigate the effect of thermal phonons on a spin qubit - the silicon-vacancy colour centre in diamond - without changing the system temperature. By controlling the strain environment of the colour centre, we tune its electronic levels to probe, control, and eventually suppress the interaction of its spin with the thermal bath. Strain control provides both large tunability of the optical transitions and significantly improved spin coherence. Finally, our findings indicate the possibility to achieve strong coupling between the silicon-vacancy spin and single phonons, which can lead to the realisation of phonon-mediated quantum gates and nonlinear quantum phononics. PMID- 29789554 TI - Synthetic cytokine receptors transmit biological signals using artificial ligands. AB - Cytokine-induced signal transduction is executed by natural biological switches, which among many others control immune-related processes. Here, we show that synthetic cytokine receptors (SyCyRs) can induce cytokine signaling using non physiological ligands. High-affinity GFP- and mCherry-nanobodies were fused to transmembrane and intracellular domains of the IL-6/IL-11 and IL-23 cytokine receptors gp130 and IL-12Rbeta1/IL-23R, respectively. Homo- and heterodimeric GFP:mCherry fusion proteins as synthetic cytokine-like ligands were able to induce canonical signaling in vitro and in vivo. Using SyCyR ligands, we show that IL-23 receptor homodimerization results in its activation and IL-23-like signal transduction. Moreover, trimeric receptor assembly induces trans phosphorylation among cytokine receptors with associated Janus kinases. The SyCyR technology allows biochemical analyses of transmembrane receptor signaling in vitro and in vivo, cell-specific activation through SyCyR ligands using transgenic animals and possible therapeutic regimes involving non-physiological targets during immunotherapy. PMID- 29789555 TI - Revealing missing charges with generalised quantum fluctuation relations. AB - The non-equilibrium dynamics of quantum many-body systems is one of the most fascinating problems in physics. Open questions range from how they relax to equilibrium to how to extract useful work from them. A critical point lies in assessing whether a system has conserved quantities (or 'charges'), as these can drastically influence its dynamics. Here we propose a general protocol to reveal the existence of charges based on a set of exact relations between out-of equilibrium fluctuations and equilibrium properties of a quantum system. We apply these generalised quantum fluctuation relations to a driven quantum simulator, demonstrating their relevance to obtain unbiased temperature estimates from non equilibrium measurements. Our findings will help guide research on the interplay of quantum and thermal fluctuations in quantum simulation, in studying the transition from integrability to chaos and in the design of new quantum devices. PMID- 29789556 TI - FoxM1-dependent RAD51 and BRCA2 signaling protects idiopathic pulmonary fibrosis fibroblasts from radiation-induced cell death. AB - Radiation therapy is critical for the control of many tumors and lung is an important dose-limiting organ that impacts radiation dose prescribed to avoid irreversible pulmonary fibrosis in cancer survivors. Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible lung disease caused by aberrantly activated lung (myo)fibroblasts. The presence of pro-fibrotic, apoptosis resistant fibroblasts in IPF promotes progressive fibrosis and may have a role in other diseases, if these resistant cells are selected for as a consequence of treatment. However, the pathological response of IPF fibroblasts to radiation compared to non-IPF lung fibroblasts is not known. To address this, we examined fibroblast viability following radiation in lung fibroblasts from IPF and non-IPF patients and the underlying mechanism that protects IPF fibroblasts from radiation-induced death. IPF fibroblasts are significantly more resistant to apoptosis compared to non-IPF lung fibroblasts, suggesting that resistance to radiation-induced cell death is a predominant mechanism leading to lung fibrosis. Analysis of gammaH2AX induction demonstrated that radiation-induced DNA damage is reduced in IPF fibroblasts and correlates to the activation of the transcription factor forkhead box M1 (FoxM1) and subsequent upregulation of DNA repair proteins RAD51 and BRCA2. FoxM1 activation occurs secondary to FoxO3a suppression in IPF fibroblasts while restoration of FoxO3a function sensitizes IPF fibroblasts to radiation-induced cell death and downregulates FoxM1, RAD51, and BRCA2. Our findings support that increased FoxO3a/FoxM1-dependent DNA repair may be integral to the preservation of death-resistant fibrotic fibroblasts after radiation and that selective targeting of radioresistant fibroblasts may mitigate fibrosis. PMID- 29789557 TI - Measuring coverage and accuracy of whole-exome sequencing in clinical context. AB - PurposeTo evaluate the coverage and accuracy of whole-exome sequencing (WES) across vendors.MethodsBlood samples from three trios underwent WES at three vendors. Relative performance of the three WES services was measured for breadth and depth of coverage. The false-negative rates (FNRs) were estimated using the segregation pattern within each trio.ResultsMean depth of coverage for all genes was 189.0, 124.9, and 38.3 for the three vendor services. Fifty-five of the American College of Medical Genetics and Genomics 56 genes, but only 56 of 63 pharmacogenes, were 100% covered at 10 * in at least one of the nine individuals for all vendors; however, there was substantial interindividual variability. For the two vendors with mean depth of coverage >120 *, analytic positive predictive values (aPPVs) exceeded 99.1% for single-nucleotide variants and homozygous indels, and sensitivities were 98.9-99.9%; however, heterozygous indels showed lower accuracy and sensitivity. Among the trios, FNRs in the offspring were 0.07 0.62% at well-covered variants concordantly called in both parents.ConclusionThe current standard of 120 * coverage for clinical WES may be insufficient for consistent breadth of coverage across the exome. Ordering clinicians and researchers would benefit from vendors' reports that estimate sensitivity and aPPV, including depth of coverage across the exome.Genetics in Medicine advance online publication, 12 April 2018; doi:10.1038/gim.2018.51. PMID- 29789558 TI - Celastrol alleviates renal fibrosis by upregulating cannabinoid receptor 2 expression. AB - Renal fibrosis is the final manifestation of various chronic kidney diseases, and no effective therapy is available to prevent or reverse it. Celastrol, a triterpene that derived from traditional Chinese medicine, is a known potent anti fibrotic agent. However, the underlying mechanisms of action of celastrol on renal fibrosis remain unknown. In this study, we found that celastrol treatment remarkably attenuated unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis. This was evidenced by the significant reduction in tubular injury; collagen deposition; accumulation of fibronectin, collagen I, and alpha-smooth muscle actin; and the expression levels of pro-fibrotic factors Vim, Cola1, and TGF-beta1 mRNA, as well as inflammatory responses. Celastrol showed similar effects in a folic acid-induced mouse renal fibrosis model. Furthermore, celastrol potentiated the expression of the anti-fibrotic factor cannabinoid receptor 2 (CB2R) in established mouse fibrotic kidney tissues and transforming growth factor beta1 (TGF-beta1)-stimulated human kidney 2 (HK-2) cells. In addition, the CB2R antagonist (SR144528) abolished celastrol-mediated beneficial effects on renal fibrosis. Moreover, UUO- or TGF-beta1-induced activation of the pro-fibrotic factor SMAD family member 3 (Smad3) was markedly inhibited by celastrol. Inhibition of Smad3 activation by an inhibitor (SIS3) markedly reduced TGF-beta1-induced downregulation of CB2R expression. In conclusion, our study provides the first direct evidence that celastrol significantly alleviated renal fibrosis, by contributing to the upregulation of CB2R expression through inhibiting Smad3 signaling pathway activation. Therefore, celastrol could be a potential drug for treating patients with renal fibrosis. PMID- 29789559 TI - Transcriptional and epigenetic modulation of autophagy promotes EBV oncoprotein EBNA3C induced B-cell survival. AB - Epstein-Barr virus (EBV) oncoprotein EBNA3C is indispensable for primary B-cell transformation and maintenance of lymphoblastoid cells outgrowth. EBNA3C usurps two putative cellular pathways-cell-cycle and apoptosis, essentially through modulating ubiquitin-mediated protein-degradation or gene transcription. In cancer cells, these two pathways are interconnected with autophagy,-a survival promoting catabolic network in which cytoplasmic material including mis/un-folded protein aggregates and damaged organelles along with intracellular pathogens are degraded and recycled in lysosomal compartments. Studies have shown that tumor viruses including EBV can manipulate autophagy as a survival strategy. Here, we demonstrate that EBNA3C elevates autophagy, which serves as a prerequisite for apoptotic inhibition and maintenance of cell growth. Using PCR based micro-array we show that EBNA3C globally accelerates autophagy gene transcription under growth limiting conditions. Reanalyzing the ENCODE ChIP-sequencing data (GSE52632 and GSE26386) followed by ChIP-PCR demonstrate that EBNA3C recruits several histone activation epigenetic marks (H3K4me1, H3K4me3, H3K9ac, and H3K27ac) for transcriptional activation of autophagy genes, notably ATG3, ATG5, and ATG7 responsible for autophagosome formation. Moreover, under growth limiting conditions EBNA3C further stimulates the autophagic response through upregulation of a number of tumor suppressor genes, notably cyclin-dependent kinase inhibitors CDKN1B (p27Kip1) and CDKN2A (p16INK4a) and autophagy mediated cell-death modulators-DRAM1 and DAPK1. Together our data highlight a new role of an essential EBV oncoprotein in regulating autophagy cascade as a survival mechanism and offer novel-targets for potential therapeutic expansion against EBV induced B cell lymphomas. PMID- 29789560 TI - Kin discrimination allows plants to modify investment towards pollinator attraction. AB - Pollinators tend to be preferentially attracted to large floral displays that may comprise more than one plant in a patch. Attracting pollinators thus not only benefits individuals investing in advertising, but also other plants in a patch through a 'magnet' effect. Accordingly, there could be an indirect fitness advantage to greater investment in costly floral displays by plants in kin structured groups than when in groups of unrelated individuals. Here, we seek evidence for this strategy by manipulating relatedness in groups of the plant Moricandia moricandioides, an insect-pollinated herb that typically grows in patches. As predicted, individuals growing with kin, particularly at high density, produced larger floral displays than those growing with non-kin. Investment in attracting pollinators was thus moulded by the presence and relatedness of neighbours, exemplifying the importance of kin recognition in the evolution of plant reproductive strategies. PMID- 29789562 TI - Author Correction: A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration. AB - The originally published version of this Article contained an error in the name of the author Salvatore Corallino, which was incorrectly given as Corallino Salvatore. This has now been corrected in both the PDF and HTML versions of the Article. PMID- 29789561 TI - L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast. AB - The synthetic yeast genome constructed by the International Synthetic Yeast Sc2.0 consortium adds thousands of loxPsym recombination sites to all 16 redesigned chromosomes, allowing the shuffling of Sc2.0 chromosome parts by the Cre-loxP recombination system thereby enabling genome evolution experiments. Here, we present L-SCRaMbLE, a light-controlled Cre recombinase for use in the yeast Saccharomyces cerevisiae. L-SCRaMbLE allows tight regulation of recombinase activity with up to 179-fold induction upon exposure to red light. The extent of recombination depends on induction time and concentration of the chromophore phycocyanobilin (PCB), which can be easily adjusted. The tool presented here provides improved recombination control over the previously reported estradiol dependent SCRaMbLE induction system, mediating a larger variety of possible recombination events in SCRaMbLE-ing a reporter plasmid. Thereby, L-SCRaMbLE boosts the potential for further customization and provides a facile application for use in the S. cerevisiae genome re-engineering project Sc2.0 or in other recombination-based systems. PMID- 29789563 TI - Analysis of Moisture Content in Beetroot using Fourier Transform Infrared Spectroscopy and by Principal Component Analysis. AB - The moisture content of beetroot varies during long-term cold storage. In this work, we propose a strategy to identify the moisture content and age of beetroot using principal component analysis coupled Fourier transform infrared spectroscopy (FTIR). Frequent FTIR measurements were recorded directly from the beetroot sample surface over a period of 34 days for analysing its moisture content employing attenuated total reflectance in the spectral ranges of 2614 4000 and 1465-1853 cm-1 with a spectral resolution of 8 cm-1. In order to estimate the transmittance peak height (T p ) and area under the transmittance curve [Formula: see text] over the spectral ranges of 2614-4000 and 1465-1853 cm 1, Gaussian curve fitting algorithm was performed on FTIR data. Principal component and nonlinear regression analyses were utilized for FTIR data analysis. Score plot over the ranges of 2614-4000 and 1465-1853 cm-1 allowed beetroot quality discrimination. Beetroot quality predictive models were developed by employing biphasic dose response function. Validation experiment results confirmed that the accuracy of the beetroot quality predictive model reached 97.5%. This research work proves that FTIR spectroscopy in combination with principal component analysis and beetroot quality predictive models could serve as an effective tool for discriminating moisture content in fresh, half and completely spoiled stages of beetroot samples and for providing status alerts. PMID- 29789564 TI - Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies. AB - Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations. PMID- 29789566 TI - Transcriptome analysis of the adult human Klinefelter testis and cellularity matched controls reveals disturbed differentiation of Sertoli- and Leydig cells. AB - The most common human sex chromosomal disorder is Klinefelter syndrome (KS; 47,XXY). Adult patients with KS display a diverse phenotype but are nearly always infertile, due to testicular degeneration at puberty. To identify mechanisms causing the selective destruction of the seminiferous epithelium, we performed RNA-sequencing of 24 fixed paraffin-embedded testicular tissue samples. Analysis of informative transcriptomes revealed 235 differentially expressed transcripts (DETs) in the adult KS testis showing enrichment of long non-coding RNAs, but surprisingly not of X-chromosomal transcripts. Comparison to 46,XY samples with complete spermatogenesis and Sertoli cell-only-syndrome allowed prediction of the cellular origin of 71 of the DETs. DACH2 and FAM9A were validated by immunohistochemistry and found to mark apparently undifferentiated somatic cell populations in the KS testes. Moreover, transcriptomes from fetal, pre-pubertal, and adult KS testes showed a limited overlap, indicating that different mechanisms are likely to operate at each developmental stage. Based on our data, we propose that testicular degeneration in men with KS is a consequence of germ cells loss initiated during early development in combination with disturbed maturation of Sertoli- and Leydig cells. PMID- 29789569 TI - Value added transformation of ubiquitous substrates into highly efficient and flexible electrodes for water splitting. AB - Herein, we present an innovative approach for transforming commonly available cellulose paper into a flexible and catalytic current collector for overall water splitting. A solution processed soak-and-coat method of electroless plating was used to render a piece of paper conducting by conformably depositing metallic nickel nanoparticles, while still retaining the open macroporous framework. Proof of-concept paper-electrodes are realized by modifying nickel-paper current collector with model electrocatalysts nickel-iron oxyhydroxide and nickel molybdenum bimetallic alloy through electrodeposition route. The paper-electrodes demonstrate exceptional activities towards oxygen evolution reaction and hydrogen evolution reaction, requiring overpotentials of 240 and 32 mV at 50 and -10 mA cm 2, respectively, even as they endure extreme mechanical stress. The generality of this approach is demonstrated by fabricating similar electrodes on cotton fabric, which also show high activity. Finally, a two-electrode paper-electrolyzer is constructed which can split water with an efficiency of 98.01%, and exhibits robust stability for more than 200 h. PMID- 29789565 TI - The wide utility of rabbits as models of human diseases. AB - Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases. Examples include syphilis, tuberculosis, HIV-AIDS, acute hepatic failure and diseases caused by noroviruses, ocular herpes, and papillomaviruses. The use of rabbits for vaccine development studies, which began with Louis Pasteur's rabies vaccine in 1881, continues today with targets that include the potentially blinding HSV-1 virus infection and HIV AIDS. Additionally, two highly fatal viral diseases, rabbit hemorrhagic disease and myxomatosis, affect the European rabbit and provide unique models to understand co-evolution between a vertebrate host and viral pathogens. PMID- 29789567 TI - Precise control of SCRaMbLE in synthetic haploid and diploid yeast. AB - Compatibility between host cells and heterologous pathways is a challenge for constructing organisms with high productivity or gain of function. Designer yeast cells incorporating the Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system provide a platform for generating genotype diversity. Here we construct a genetic AND gate to enable precise control of the SCRaMbLE method to generate synthetic haploid and diploid yeast with desired phenotypes. The yield of carotenoids is increased to 1.5-fold by SCRaMbLEing haploid strains and we determine that the deletion of YEL013W is responsible for the increase. Based on the SCRaMbLEing in diploid strains, we develop a strategy called Multiplex SCRaMbLE Iterative Cycling (MuSIC) to increase the production of carotenoids up to 38.8-fold through 5 iterative cycles of SCRaMbLE. This strategy is potentially a powerful tool for increasing the production of bio-based chemicals and for mining deep knowledge. PMID- 29789571 TI - A novel extracellular vesicle-associated endodeoxyribonuclease helps Streptococcus pneumoniae evade neutrophil extracellular traps and is required for full virulence. AB - Streptococcus pneumoniae (pneumococcus) is a major bacterial pathogen that causes pneumonia and septicemia in humans. Pneumococci are cleared from the host primarily by antibody dependent opsonophagocytosis by phagocytes like neutrophils. Neutrophils release neutrophil extracellular traps (NETs) on contacting pneumococci. NETs immobilize pneumococci and restrict its dissemination in the host. One of the strategies utilized by pneumococci to evade the host immune response involves use of DNase(s) to degrade NETs. We screened the secretome of autolysin deficient S. pneumoniae to identify novel DNase(s). Zymogram analysis revealed 3 bands indicative of DNase activity. Mass spectrometric analysis led to the identification of TatD as a potential extracellular DNase. Recombinant TatD showed nucleotide sequence-independent endodeoxyribonuclease activity. TatD was associated with extracellular vesicles. Pneumococcal secretome degraded NETs from human neutrophils. Extracellular vesicle fraction from tatD deficient strain showed little NET degrading activity. Recombinant TatD efficiently degraded NETs. tatD deficient pneumococci showed lower bacterial load in lungs, blood and spleen in a murine sepsis model compared to wildtype strain, and showed less severe lung pathology and compromised virulence. This study provides insights into the role of a novel extracellular DNase in evasion of the innate immune system. PMID- 29789570 TI - Structural resolution of inorganic nanotubes with complex stoichiometry. AB - Determination of the atomic structure of inorganic single-walled nanotubes with complex stoichiometry remains elusive due to the too many atomic coordinates to be fitted with respect to X-ray diffractograms inherently exhibiting rather broad features. Here we introduce a methodology to reduce the number of fitted variables and enable resolution of the atomic structure for inorganic nanotubes with complex stoichiometry. We apply it to recently synthesized methylated aluminosilicate and aluminogermanate imogolite nanotubes of nominal composition (OH)3Al2O3Si(Ge)CH3. Fitting of X-ray scattering diagrams, supported by Density Functional Theory simulations, reveals an unexpected rolling mode for these systems. The transferability of the approach opens up for improved understanding of structure-property relationships of inorganic nanotubes to the benefit of fundamental and applicative research in these systems. PMID- 29789568 TI - Deficiency of PRKD2 triggers hyperinsulinemia and metabolic disorders. AB - Hyperinsulinemia is the earliest symptom of insulin resistance (IR), but a causal relationship between the two remains to be established. Here we show that a protein kinase D2 (PRKD2) nonsense mutation (K410X) in two rhesus monkeys with extreme hyperinsulinemia along with IR and metabolic defects by using extreme phenotype sampling and deep sequencing analyses. This mutation reduces PRKD2 at both the mRNA and the protein levels. Taking advantage of a PRKD2-KO mouse model, we demonstrate that PRKD2 deletion triggers hyperinsulinemia which precedes to IR and metabolic disorders in the PRKD2 ablation mice. PRKD2 deficiency promotes beta-cell insulin secretion by increasing the expression and activity of L-type Ca2+ channels and subsequently augmenting high glucose- and membrane depolarization-induced Ca2+ influx. Altogether, these results indicate that down regulation of PRKD2 is involved in the pathogenesis of hyperinsulinemia which, in turn, results in IR and metabolic disorders. PMID- 29789572 TI - Glioblastoma single-cell microRaman analysis under stress treatments. AB - Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor characterized by highly heterogeneous subpopulations. In order to reveal the heterogeneous cell response, single cell analysis is an essential requirement. In this study, optical microscopy and Raman microspectroscopy were used to follow the stress response of U251 single cells adherent on a silicon substrate. Cultured cells on silicon substrate were treated with hydrogen peroxide to promote apoptosis. Under these conditions expected changes occurred after a few hours and were revealed by the reduction of cytochrome c, lipid, nucleic acid and protein Raman signals: this ensured the possibility to analyse U251 cell line as grown on Si substrate, and to monitor the response of single cells to stress conditions. As a consequence, we used microRaman to monitor the effects induced by nutrient depletion: a fast change of Raman spectra showed two different sub populations of sensible and resistant U251 cells. Furthermore, spectral variations after DMSO addition were associated to volume changes and confirmed by morphological analysis. Thus, our results highlight the sensitivity of Raman microspectroscopy to detect rapid variations of macromolecule concentration due to oxidative stress and/or cell volume changes at the single cell level. PMID- 29789574 TI - Helicobacter pylori-infected C57BL/6 mice with different gastrointestinal microbiota have contrasting gastric pathology, microbial and host immune responses. AB - C57BL/6 (B6) mice from Taconic Sciences (Tac) and the Jackson Laboratory (Jax) were infected with H. pylori PMSS1 (Hp) for 16 week; there was no significant difference in the gastric histologic activity index between Hp infected Tac and Jax B6. However, the degree of gastric mucous metaplasia and Th1-associated IgG2c levels in response to Hp infection were increased in Tac mice over Jax mice, whereas the colonization levels of gastric Hp were higher by 8-fold in Jax B6 compared with Tac B6. Additionally, mRNA expression of gastric Il-1beta, Il-17A and RegIIIgamma were significantly lower in the infected Tac compared to the infected Jax mice. There were significant differences in the microbial community structures in stomach, colon, and feces between Jax and Tac B6 females. Differences in gastric microbial communities between Jax and Tac B6 females are predicted to affect the metagenome. Moreover, Hp infection perturbed the microbial community structures in the stomach, colon and feces of Jax mice, but only altered the colonic microbial composition of Tac mice. Our data indicate that the GI microbiome of Tac B6 mice is compositionally distinct from Jax B6 mice, which likely resulted in different pathological, immunological, and microbial responses to Hp infection. PMID- 29789576 TI - Ventral striatal response during decision making involving risk and reward is associated with future binge drinking in adolescents. AB - Beginning to engage in heavy alcohol use during adolescence, as opposed to later in life, is associated with elevated risk for a variety of negative consequences, including the development of an alcohol use disorder. Behavioral studies suggest that poor decision making predicts alcohol use during adolescence; however, more research is needed to determine the neurobiological risk factors that underlie this association. Using functional magnetic resonance imaging, brain activation during decision making involving risk and reward was assessed in 47 adolescents (14-15 years old) with no significant history or alcohol or drug use. After baseline assessment, participants completed follow-up interviews every 3 months to assess the duration to onset of binge drinking. Adolescents who made a greater number of risky selections and had greater activation in the nucleus accumbens, precuneus, and occipital cortex during decision making involving greater potential for risk and reward began binge drinking sooner. Findings suggest that heightened activation of reward circuitry during decision making under risk is a neurobiological risk factor for earlier onset of binge drinking. Furthermore, brain activation was a significant predictor of onset to binge drinking, even after controlling for decision-making behavior, suggesting that neurobiological markers may provide additional predictive validity over behavioral assessments. Interventions designed to modify these behavioral and neurobiological risk factors may be useful for curbing heavy alcohol use during adolescence. PMID- 29789573 TI - High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing. AB - Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large scale screening of functional SNPs at disease risk loci. PMID- 29789575 TI - Tamoxifen-induced knockdown of the mitochondrial calcium uniporter in Thy1 expressing neurons protects mice from hypoxic/ischemic brain injury. AB - The mitochondrial calcium uniporter (MCU) mediates high-capacity mitochondrial calcium uptake that stimulates energy production. However, excessive MCU activity can cause ischemic heart injury. To examine if the MCU is also involved in hypoxic/ischemic (HI) brain injury, we have generated conditional MCU knockout mice by tamoxifen (TMX) administration to adult MCU-floxed (MCUfl/fl) mice expressing a construct encoding Thy1-cre/ERT2-eYFP. Relative to TMX/Thy1-cre/ERT2 eYFP controls, HI-induced sensorimotor deficits, forebrain neuron loss and mitochondrial damage were decreased for conditional MCU knockout mice. MCU knockdown by siRNA-induced silencing in cortical neuron cultures also reduced cell death and mitochondrial respiratory deficits following oxygen-glucose deprivation. Furthermore, MCU silencing did not produce metabolic abnormalities in cortical neurons observed previously for global MCU nulls that increased reliance on glycolysis for energy production. Based on these findings, we propose that brain-penetrant MCU inhibitors have strong potential to be well-tolerated and highly-efficacious neuroprotectants for the acute management of ischemic stroke. PMID- 29789577 TI - Long non-coding RNA Gm2199 rescues liver injury and promotes hepatocyte proliferation through the upregulation of ERK1/2. AB - Long non-coding RNAs (lncRNAs) are a new class of regulators of various human diseases. This study was designed to explore the potential role of lncRNAs in experimental hepatic damage. In vivo hepatic damage in mice and in vitro hepatocyte damage in AML12 and NCTC1469 cells were induced by carbon tetrachloride (CCl4) treatments. Expression profiles of lncRNAs and mRNAs were analyzed by microarray. Bioinformatics analyses were conducted to predict the potential functions of differentially expressed lncRNAs with respect to hepatic damage. Overexpression of lncRNA Gm2199 was achieved by transfection of the pEGFP N1-Gm2199 plasmid in vitro and adeno-associated virus-Gm2199 in vivo. Cell proliferation and viability was detected by cell counting kit-8 and 5-ethynyl-2' deoxyuridine assay. Protein and mRNA expressions of extracellular signal regulated kinase-1/2 (ERK1/2) were detected by western blot and quantitative real time reverse-transcription PCR (qRT-PCR). Microarray analysis identified 190 and 148 significantly differentially expressed lncRNAs and mRNAs, respectively. The analyses of lncRNA-mRNA co-expression and lncRNA-biological process networks unraveled potential roles of the differentially expressed lncRNAs including Gm2199 in the pathophysiological processes leading to hepatic damage. Gm2199 was downregulated in both damaged livers and hepatocyte lines. Overexpression of Gm2199 restored the reduced proliferation of damaged hepatocyte lines and increased the expression of ERK1/2. Overexpression of Gm2199 also promoted the proliferation and viability of normal hepatocyte lines and increased the level of p-ERK1/2. Overexpression of Gm2199 in vivo also protected mouse liver injury induced by CCl4, evidenced by more proliferating hepatocytes, less serum alanine aminotransferase, less serum aspartate aminotransferase, and decreased hepatic hydroxyproline. The ability of Gm2199 to maintain hepatic proliferation capacity indicates it as a novel anti-liver damage lncRNA. PMID- 29789578 TI - SK channel activation is neuroprotective in conditions of enhanced ER mitochondrial coupling. AB - Alterations in the strength and interface area of contact sites between the endoplasmic reticulum (ER) and mitochondria contribute to calcium (Ca2+) dysregulation and neuronal cell death, and have been implicated in the pathology of several neurodegenerative diseases. Weakening this physical linkage may reduce Ca2+ uptake into mitochondria, while fortifying these organelle contact sites may promote mitochondrial Ca2+ overload and cell death. Small conductance Ca2+ activated K+ (SK) channels regulate mitochondrial respiration, and their activation attenuates mitochondrial damage in paradigms of oxidative stress. In the present study, we enhanced ER-mitochondrial coupling and investigated the impact of SK channels on survival of neuronal HT22 cells in conditions of oxidative stress. Using genetically encoded linkers, we show that mitochondrial respiration and the vulnerability of neuronal cells to oxidative stress was inversely linked to the strength of ER-mitochondrial contact points and the increase in mitochondrial Ca2+ uptake. Pharmacological activation of SK channels provided protection against glutamate-induced cell death and also in conditions of increased ER-mitochondrial coupling. Together, this study revealed that SK channel activation provided persistent neuroprotection in the paradigm of glutamate-induced oxytosis even in conditions where an increase in ER mitochondrial coupling potentiated mitochondrial Ca2+ influx and impaired mitochondrial bioenergetics. PMID- 29789579 TI - Endogenous authentic OCT4A proteins directly regulate FOS/AP-1 transcription in somatic cancer cells. AB - OCT4A is well established as a master transcription factor for pluripotent stem cell (PSC) self-renewal and a pioneer factor for initiating somatic cell reprogramming, yet its presence and functionality in somatic cancer cells remain controversial and obscure. By combining the CRISPR-Cas9-based gene editing with highly specific PCR assays, highly sensitive immunoassays, and mass spectrometry, we provide unequivocal evidence here that full-length authentic OCT4A transcripts and proteins were both present in somatic cancer cells, and OCT4A proteins were heterogeneously expressed in the whole cell population and when expressed, they are predominantly localized in cell nucleus. Despite their extremely low abundance (approximately three orders of magnitude lower than in PSCs), OCT4A proteins bound to the promoter/enhancer regions of the AP-1 transcription factor subunit c-FOS gene and critically regulated its transcription. Knocking out OCT4A in somatic cancer cells led to dramatic reduction of the c-FOS protein level, aberrant AP-1 signaling, dampened self-renewal capacity, deficient cell migration that were associated with cell growth retardation in vitro and in vivo, and their enhanced sensitivity to anticancer drugs. Taken together, we resolve the long standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. PMID- 29789580 TI - The Effects of Anti-LAP Monoclonal Antibody Down-regulation of CD4+LAP+ T Cells on Allogeneic Corneal Transplantation in Mice. AB - CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN gamma+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-gamma, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-beta1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes. PMID- 29789581 TI - Intron retention and nuclear loss of SFPQ are molecular hallmarks of ALS. AB - Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate ubiquitously expressed regulators of RNA processing. To understand the molecular impact of ALS-causing mutations on neuronal development and disease, we analysed transcriptomes during in vitro differentiation of motor neurons (MNs) from human control and patient-specific VCP mutant induced-pluripotent stem cells (iPSCs). We identify increased intron retention (IR) as a dominant feature of the splicing programme during early neural differentiation. Importantly, IR occurs prematurely in VCP mutant cultures compared with control counterparts. These aberrant IR events are also seen in independent RNAseq data sets from SOD1- and FUS-mutant MNs. The most significant IR is seen in the SFPQ transcript. The SFPQ protein binds extensively to its retained intron, exhibits lower nuclear abundance in VCP mutant cultures and is lost from nuclei of MNs in mouse models and human sporadic ALS. Collectively, we demonstrate SFPQ IR and nuclear loss as molecular hallmarks of familial and sporadic ALS. PMID- 29789583 TI - TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation. AB - Tripartite motif-containing 50 (TRIM50) belongs to the tripartite motif (TRIM) protein family, which has been implicated in the pathogenesis of multiple cancers. However, the role of TRIM50 in hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that TRIM50 expression was significantly decreased in liver cancer tissues compared with corresponding non-cancerous liver tissues, and its decreased expression was significantly correlated with advanced disease progression. Gain-of-function assay by exogenous overexpression of TRIM50 in HCC cells showed that proliferation, colony formation, migration and invasion of HCC cells were significantly inhibited, whereas loss-of-function assay by TRIM50 knockdown showed that these malignant behaviors of HCC cells were significantly increased. Further investigation showed that TRIM50 could directly bind with SNAIL and induced K-48 linked poly-ubiquitous degradation of SNAIL protein, which further reversed SNAIL-mediated epithelial-to-mesenchymal transition (EMT) process of HCC cells. In vivo assay by xenograft tumor model verified the antitumor effect of TRIM50 on HCC. Taken together, these results showed that TRIM50 acted as a tumor suppressor in HCC cells by directly targeting SNAIL and reversing EMT, which further indicated that positive modulation of TRIM50 might be a novel therapeutic strategy for SNAIL overexpressed HCC cells. PMID- 29789582 TI - The concordance between upper and lower respiratory microbiota in children with Mycoplasma pneumoniae pneumonia. AB - In recent years, the morbidity of Mycoplasma pneumoniae pneumonia (MPP) has dramatically increased in China. An increasing number of studies indicate that an imbalance in the respiratory microbiota is associated with respiratory infection. We selected 28 hospitalized patients infected with M. pneumoniae and 32 healthy children. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from healthy children, whereas NP, OP and bronchoalveolar lavage (BAL) specimens were collected from patients. Microbiota analysis was performed on all microbial samples using 16 S ribosomal RNA (16 S rRNA) sequencing. The NP microbial samples in healthy children were divided into two groups, which were dominated by either Staphylococcus or mixed microbial components. The respiratory microbiota in pneumonia patients harbored a lower microbial diversity compared to healthy children, and both the NP and OP microbiota of patients differed significantly from that of healthy children. Hospitalized MPP children with a higher abundance of Mycoplasma in the BAL fluid (BALF) microbiota tended to suffer longer hospitalization lengths and higher peak fevers and serum C-reactive protein levels. Concordance analysis explained the succession of imbalanced NP microbiota to the OP and lung in diseased children. However, the association of the abundance of Mycoplasma in BALF microbiota with that in NP or OP microbiota varied among individuals, which suggested the sensitivity of BALF in MPP diagnostics, mirroring MPP severity. PMID- 29789584 TI - RTK-RAS pathway mutation is enriched in myeloid sarcoma. PMID- 29789586 TI - Paddy-upland rotation for sustainable agriculture with regards to diverse soil microbial community. AB - Diverse soil microbial community is determinant for sustainable agriculture. Rich microbial diversity has presumably improved soil health for economic crops to grow. In this work, the benefits of paddy-upland rotation on soil microbial diversity and specific microbes are thus intensively explored. The microbiome from multiple factor experiment (three fertilizations coupled with two rotation systems) were investigated by novel enrichment and co-occurrence analysis in a field well maintained for 25 years. Using next-generation sequencing technique, we firstly present explicit evidence that different rotation systems rather than fertilizations mightily governed the soil microbiome. Paddy-upland rotation (R1) obviously increase more microbial diversity than upland rotation (R2) whether organic (OF), chemical (CF) or integrated fertilizers (IF) were concomitantly applied. Besides, the specific bacterial composition dominated in OF soil is more similar to that of R1 than to CF, suggesting that paddy-upland rotation might be the best option for sustainable agriculture if chemical fertilizer is still required. Interestingly, the pot bioassay verified clearly the novel analysis prediction, illustrating that greater microbial diversity and specific microbial composition correlated significantly with disease resistance. This finding highlights the eminence of paddy-upland rotation in promoting microbial diversity and specific microbial compositions, preserving soil health for sustainable agriculture. PMID- 29789587 TI - More than an information service: are counselling skills needed by genetics professionals in the genomic era? PMID- 29789585 TI - Hypoxia induces senescence of bone marrow mesenchymal stem cells via altered gut microbiota. AB - Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal D-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded D galactose. Replenishing chronic hypoxic rats with Lactobacillus reduced the accumulation of D-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus induced D-galactose accumulation. PMID- 29789588 TI - Renormalization group theory for percolation in time-varying networks. AB - Motivated by multi-hop communication in unreliable wireless networks, we present a percolation theory for time-varying networks. We develop a renormalization group theory for a prototypical network on a regular grid, where individual links switch stochastically between active and inactive states. The question whether a given source node can communicate with a destination node along paths of active links is equivalent to a percolation problem. Our theory maps the temporal existence of multi-hop paths on an effective two-state Markov process. We show analytically how this Markov process converges towards a memoryless Bernoulli process as the hop distance between source and destination node increases. Our work extends classical percolation theory to the dynamic case and elucidates temporal correlations of message losses. Quantification of temporal correlations has implications for the design of wireless communication and control protocols, e.g. in cyber-physical systems such as self-organized swarms of drones or smart traffic networks. PMID- 29789589 TI - Characterization of different bubble formulations for blood-brain barrier opening using a focused ultrasound system with acoustic feedback control. AB - Focused ultrasound combined with bubble-based agents serves as a non-invasive way to open the blood-brain barrier (BBB). Passive acoustic detection was well studied recently to monitor the acoustic emissions induced by the bubbles under ultrasound energy, but the ability to perform reliable BBB opening with a real time feedback control algorithm has not been fully evaluated. This study focuses on characterizing the acoustic emissions of different types of bubbles: Optison, Definity, and a custom-made nanobubble. Their performance on reliable BBB opening under real-time feedback control based on acoustic detection was evaluated both in-vitro and in-vivo. The experiments were conducted using a 0.5 MHz focused ultrasound transducer with in-vivo focal pressure ranges from 0.1-0.7 MPa. Successful feedback control was achieved with all three agents when combining with infusion injection. Localized opening was confirmed with Evans blue dye leakage. Microscopic images were acquired to review the opening effects. Under similar total gas volume, nanobubble showed a more reliable opening effect compared to Optison and Definity (p < 0.05). The conclusions obtained from this study confirm the possibilities of performing stable opening using a feedback control algorithm combined with infusion injection. It also opens another potential research area of BBB opening using sub-micron bubbles. PMID- 29789590 TI - Heterozygous diploid and interspecies SCRaMbLEing. AB - SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) is a genome restructuring technique that can be used in synthetic genomes such as that of Sc2.0, the synthetic yeast genome, which contains hundreds to thousands of strategically positioned loxPsym sites. SCRaMbLE has been used to induce rearrangements in yeast strains harboring one or more synthetic chromosomes, as well as plasmid DNA in vitro and in vivo. Here we describe a collection of heterozygous diploid strains produced by mating haploid semisynthetic Sc2.0 strains to haploid native parental strains. We subsequently demonstrate that such heterozygous diploid strains are more robust to the effects of SCRaMbLE than haploid semisynthetic strains, rapidly improve rationally selected phenotypes in SCRaMbLEd heterozygous diploids, and establish that multiple sets of independent genomic rearrangements are able to lead to similar phenotype enhancements. Finally, we show that heterozygous diploid SCRaMbLE can also be carried out in interspecies hybrid strains. PMID- 29789593 TI - [177Lu]PSMA-617 radionuclide therapy shows promise. PMID- 29789591 TI - A study of wound repair in Dictyostelium cells by using novel laserporation. AB - We examined the mechanism of cell membrane repair in Dictyostelium cells by using a novel laser-based cell poration method. The dynamics of wound pores opening and closing were characterized by live imaging of fluorescent cell membrane proteins, influx of fluorescent dye, and Ca2+ imaging. The wound closed within 2-4 sec, depending on the wound size. Cells could tolerate a wound size of less than 2.0 um. In the absence of Ca2+ in the external medium, the wound pore did not close and cells ruptured. The release of Ca2+ from intracellular stores also contributed to the elevation of cytoplasmic Ca2+ but not to wound repair. Annexin C1 immediately accumulated at the wound site depending on the external Ca2+ concentration, and annexin C1 knockout cells had a defect in wound repair, but it was not essential. Dictyostelium cells were able to respond to multiple repeated wounds with the same time courses, in contrast to previous reports showing that the first wound accelerates the second wound repair in fibroblasts. PMID- 29789592 TI - Allogenic and Autogenic Signals in the Stratigraphic Record of the Deep-Sea Bengal Fan. AB - The Himalayan-sourced Ganges-Brahmaputra river system and the deep-sea Bengal Fan represent Earth's largest sediment-dispersal system. Here we present detrital zircon U-Pb provenance data from Miocene to middle Pleistocene Bengal Fan turbidites, and evaluate the influence of allogenic forcing vs. autogenic processes on signal propagation from the Himalaya to the deep sea. Our data record the strong tectonic and climatic forcing characteristic of the Himalayan system: after up to 2500 km of river transport, and >1400 km of transport by turbidity currents, the U-Pb record faithfully represents Himalayan sources. Moreover, specific U-Pb populations record Miocene integration of the Brahmaputra drainage with the Asian plate, as well as the rapid Plio-Pleistocene incision through, and exhumation of, the eastern Himalayan syntaxis. The record is, however, biased towards glacial periods when rivers were extended across the shelf in response to climate-forced sea-level fall, and discharged directly to slope canyons. Finally, only part of the record represents a Ganges or Brahmaputra provenance end-member, and most samples represent mixing from the two systems. Mixing or the lack thereof likely represents the fingerprint of autogenic delta-plain avulsions, which result in the two rivers delivering sediment separately to a shelf-margin canyon or merging together as they do today. PMID- 29789595 TI - Endocide-Induced Abnormal Growth Forms of Invasive Giant Salvinia (Salvinia molesta). AB - Giant salvinia (Salvinia molesta) is one of the most noxious invasive species in the world. The fern is known to have primary, secondary, and tertiary growth forms, which are also commonly hypothesized as growth stages. The identification of these forms is primarily based on the size and folding status of the floating leaves. However, we identified 12 forms in the greenhouse and the field. Our experiments showed that the folding of floating leaves is a reversible trait dependent on water access. The floating leaves quickly fold in response to water shortage, reducing water loss and needs, decreasing growth, and avoiding trichome damage. The leaves re-open to allow trichomes repel water and enhance growth when having adequate water supply. Larger secondary or tertiary forms do not produce small-leaf primary forms without high intensity stress. These results do not support the hypothesis that three growth forms represent sequential growth stages. The abnormal small-leaf forms are the result of endocide-induced autotoxicity and some of them never grow into other forms. The development of abnormal forms and reversible leaf folding strategy in response to high stress along with rapid asexual reproduction are major adaptive traits contributing to the invasiveness of S. molesta. PMID- 29789594 TI - In vitro DNA SCRaMbLE. AB - The power of synthetic biology has enabled the expression of heterologous pathways in cells, as well as genome-scale synthesis projects. The complexity of biological networks makes rational de novo design a grand challenge. Introducing features that confer genetic flexibility is a powerful strategy for downstream engineering. Here we develop an in vitro method of DNA library construction based on structural variation to accomplish this goal. The "in vitro SCRaMbLE system" uses Cre recombinase mixed in a test tube with purified DNA encoding multiple loxPsym sites. Using a beta-carotene pathway designed for expression in yeast as an example, we demonstrate top-down and bottom-up in vitro SCRaMbLE, enabling optimization of biosynthetic pathway flux via the rearrangement of relevant transcription units. We show that our system provides a straightforward way to correlate phenotype and genotype and is potentially amenable to biochemical optimization in ways that the in vivo system cannot achieve. PMID- 29789596 TI - Cervical vagus nerve morphometry and vascularity in the context of nerve stimulation - A cadaveric study. AB - Vagus nerve stimulation (VNS) has become a well-established therapy for epilepsy and depression, and is emerging to treat inflammatory disease, with the cervical vagus nerve (CVN) as major stimulation site. CVN morphometries are missing for VNS, considering its variability. Morphometric data were obtained from CVNs in 27 cadavers, including branching patterns and histology. Cross-sectional area, greater and lesser diameters averaged 7.2 +/- 3.1 mm2, 5.1 +/- 1.5 and 4.1 +/- 1.3 mm, and were <=11.0 mm2, <=7.0 and <=5.8 mm in 90% of the specimens, respectively. Midline distance (position lateral to the laryngeal eminence) and skin distance (anterior-posterior from skin) averaged 34.5 +/- 6.2 and 36.2 +/- 9.4 mm, <=49.0 and <=41.0 mm in 90%, respectively. Nerve dimensions and surface topography correlated closely, but without gender-, side- or branching-dependent differences. The nerve fascicle number averaged 5.2 +/- 3.5. Vagal arteries were observed in 49% of the cases. Negative correlations were found for age and cross sectional area, as well as subperineural vessel count. Detailed anatomical data on the CVN and its vascularity are given, forming the morphometric basis for VNS refinement, filling an evident gap in light of the CVN being a structure with variable positions and branching. A 35 * 35-mm rule may apply for the CVN position, irrespective of branching or positional variation. PMID- 29789597 TI - Enhancer of zeste homolog 2-catalysed H3K27 trimethylation plays a key role in acute-on-chronic liver failure via TNF-mediated pathway. AB - Acute-on-chronic liver failure is mainly due to host immunity self-destruction. The histone H3 lysine 27 (H3K27) trimethylating enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene expression and regulates immunity, also involves pathogenesis of several liver diseases. The current study was to determine the role of methyltransferase EZH2 and its catalysed H3K27 trimethylation (H3K27me3) in liver failure, and to further investigate the potential target for liver failure treatment. EZH2 and its catalysed H3K27me3 were determined in peripheral blood mononuclear cells (PBMC) from liver failure patients and Kupffer cells from experimental mice. Furthermore, GSK126 (an inhibitor for EZH2 trimethylation function) was applied in liver failure mice in vivo, and lipopolysaccharide-stimulated mononuclear cells in vitro. EZH2 and H3K27me3 were significantly upregulated in human PBMC from liver failure patients or murine Kupffer cells from the liver failure animals, respectively. GSK126 ameliorated disease severity in liver failure mice, which maybe attribute to down regulate circulating and hepatic proinflammatory cytokines, especially TNF via reducing H3K27me3. In-depth chromatin immunoprecipitation analysis unravelled that decreased enrichment of H3K27me3 on Tnf promotor, resulting in TNF elevation in Kupffer cells from liver failure mice. Nuclear factor kappa B (NF-kappaB) and protein kinase B (Akt) signalling pathways were activated upon lipopolysaccharide stimulation, but attenuated by using GSK126, accompanied with decreased TNF in vitro. In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-kappaB and Akt signalling pathways. PMID- 29789598 TI - Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence. AB - Cancer recurrence after initial diagnosis and treatment is a major cause of breast cancer (BC) mortality, which results from the metastatic outbreak of dormant tumour cells. Alterations in the tumour microenvironment can trigger signalling pathways in dormant cells leading to their proliferation. However, processes involved in the initial and the long-term survival of disseminated dormant BC cells remain largely unknown. Here we show that autophagy is a critical mechanism for the survival of disseminated dormant BC cells. Pharmacologic or genetic inhibition of autophagy in dormant BC cells results in significantly decreased cell survival and metastatic burden in mouse and human 3D in vitro and in vivo preclinical models of dormancy. In vivo experiments identify autophagy gene autophagy-related 7 (ATG7) to be essential for autophagy activation. Mechanistically, inhibition of the autophagic flux in dormant BC cells leads to the accumulation of damaged mitochondria and reactive oxygen species (ROS), resulting in cell apoptosis. PMID- 29789599 TI - Exercise activates the PI3K-AKT signal pathway by decreasing the expression of 5alpha-reductase type 1 in PCOS rats. AB - Hyperandrogenism and hyperinsulinemia are main clinical endocrine features of PCOS. Exercise can adjust the androgen level, as well as increase the sensitivity of insulin by activating PI3K-Akt insulin signaling pathways. 5alphaR1 has certain effects on insulin resistance and can synthesize dihydrotestosterone by metabolizing testosterone. So 5alphaR1 may be the target of androgen and insulin for exercise-induced regulation. To investigate the role of 5alphaR1 in the PI3K Akt signaling pathway in skeletal muscle of PCOS rats activated by exercise, fifty-four female rats were randomly divided into the PCOS group (n = 42) and the control group(n = 12). After injection of testosterone propionate for 28 days, the remaining 36 rats in the PCOS group were randomly assigned to six groups: the sedentary group (PS, n = 6), sedentary and 5alphaRI (5alpha-reductase inhibitor) group (PS + RI, n = 6), sedentary and 5alphaR2I (5alpha-reductase type 2 selective inhibitor) group (PS + R2I, n = 6), exercise group (PE, n = 6), exercise and 5alphaRI group (PE + RI, n = 6), and exercise and 5alphaR2I group (PE + R2I, n = 6). The rats undergoing exercise were trained to swim for 14 days. Finasteride (5alpha-reductase type 2 selective inhibitor) and dutasteride (5alpha reductase inhibitor) were administered once daily and were dosed based on weight. At the end, the expression of 5alphaR1 proteins, the phosphorylation level of PI3K and AKT, were determined by Western blot. The PCOS non-exercise group and the PE + RI group displayed significantly lower phosphorylation of Akt, PI3K p85 and GLUT4 expression, while in the PE + R2I group, the level of Akt phosphorylation and PI3K p85 expression was significantly higher than that of the PCOS non-exercise group and the PE + RI group. In summary, our study demonstrated that exercise can activate the PI3K/AKT signal pathway of PCOS rats by decreasing the expression of 5alphaR1. PMID- 29789600 TI - Hamiltonian path analysis of viral genomes. PMID- 29789601 TI - HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer. AB - High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural transcription factor, participates in a number of tumor biological processes. However, its effect on cervical cancer remains largely indistinct. In this study, we found that HMGA1 was generally overexpressed in cervical cancer tissues and was positively correlated with lymph node metastasis and advanced clinical stage. Via exogenously increasing or decreasing the expression of HMGA1, we showed that HMGA1 affected the proliferation, colony formation, migration and invasion of cervical cancer cells in vitro. Rescue experiments suggested that miR-221/222 could partly reverse HMGA1-mediated migration and invasion processes. Mechanistically, we discovered that HMGA1 accelerated the G1/S phase transition by regulating the expression of cyclin D1 and cyclin E1, which was consistent with the results of the in vivo experiment. Furthermore, we found that HMGA1 regulated the expression of the miR-221/222 cluster at the transcriptional level and that miR-221/222 targeted the 3'UTR of tissue inhibitor of metalloproteinases 3(TIMP3). We propose a fresh perspective that HMGA1 participates in the migration and invasion process via the miR-221/222-TIMP3-MMP2/MMP9 axis in cervical cancer. In summary, our study identified a critical role played by HMGA1 in the progression of cervical cancer and the potential mechanisms by which exerts its effects, suggesting that targeting HMGA1-related pathways could be conducive to the therapies for cervical cancer. PMID- 29789603 TI - Vorinostat and quinacrine have synergistic effects in T-cell acute lymphoblastic leukemia through reactive oxygen species increase and mitophagy inhibition. AB - Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat induced cell death at a non-toxic concentration. Compared to the single treatment, QC plus vorinostat significantly induced apoptosis, disrupted the mitochondrial transmembrane potential, and decreased Mcl-1 and Bcl-2/Bax ratio. Interestingly, the application of QC plus vorinostat resulted in mitophagy blockade, as reflected by the increase in the K63-linked ubiquitination of mitochondria protein and the formation of mitochondrial aggresomes. QC plus vorinostat markedly increased the reactive oxygen species (ROS) level in cells. Moreover, the ROS scavenger N-acetylcysteine (NAC) abrogated QC plus vorinostat induced ROS, decreased the ubiquitination of mitochondria proteins, and cell death. Finally, using a xenograft mouse model, we demonstrated that QC plus vorinostat significantly reduced cell proliferation and induced cell death in vivo. Taken together, our results showed that the combination of QC with vorinostat may represent a novel regimen for the treatment of T-cell acute lymphoblastic leukemia, which deserves clinical evaluation in the future. PMID- 29789602 TI - Hygroscopic compounds in spider aggregate glue remove interfacial water to maintain adhesion in humid conditions. AB - Adhesion in humid environments is fundamentally challenging because of the presence of interfacial bound water. Spiders often hunt in wet habitats and overcome this challenge using sticky aggregate glue droplets whose adhesion is resistant to interfacial failure under humid conditions. The mechanism by which spider aggregate glue avoids interfacial failure in humid environments is still unknown. Here, we investigate the mechanism of aggregate glue adhesion by using interface-sensitive spectroscopy in conjunction with infrared spectroscopy. We demonstrate that glycoproteins act as primary binding agents at the interface. As humidity increases, we observe reversible changes in the interfacial secondary structure of glycoproteins. Surprisingly, we do not observe liquid-like water at the interface, even though liquid-like water increases inside the bulk with increasing humidity. We hypothesize that the hygroscopic compounds in aggregate glue sequester interfacial water. Using hygroscopic compounds to sequester interfacial water provides a novel design principle for developing water resistant synthetic adhesives. PMID- 29789604 TI - Plasma membrane LAT activation precedes vesicular recruitment defining two phases of early T-cell activation. AB - The relative importance of plasma membrane-localized LAT versus vesicular LAT for microcluster formation and T-cell receptor (TCR) activation is unclear. Here, we show the sequence of events in LAT microcluster formation and vesicle delivery, using lattice light sheet microscopy to image a T cell from the earliest point of activation. A kinetic lag occurs between LAT microcluster formation and vesicular pool recruitment to the synapse. Correlative 3D light and electron microscopy show an absence of vesicles at microclusters at early times, but an abundance of vesicles as activation proceeds. Using TIRF-SIM to look at the activated T-cell surface with high resolution, we capture directed vesicle movement between microclusters on microtubules. We propose a model in which cell surface LAT is recruited rapidly and phosphorylated at sites of T-cell activation, while the vesicular pool is subsequently recruited and dynamically interacts with microclusters. PMID- 29789606 TI - The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores. AB - INTRODUCTION: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. METHODS: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil- platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. RESULTS: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. CONCLUSIONS: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use. PMID- 29789605 TI - Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection. AB - Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions. The across-region differences in fMRI signal changes relative to area 3a/3b between tactile and FUS conditions also indicate that FUS modulated the tactile network differently. The significantly faster rising (>1 sec) fMRI signals elicited by direct FUS stimulation at the targeted cortical region suggest that a different neural hemodynamic coupling mechanism may be involved in generating fMRI signals. This is the first demonstration of imaging neural excitation effects of FUS with BOLD fMRI on a specific functional circuit in non human primates. PMID- 29789607 TI - Point of care microspirometry to facilitate the COPD diagnostic process in primary care: a clustered randomised trial. AB - We studied if pre-bronchodilator FEV1/FEV6 determinations with microspirometers by GPs improve the diagnostic process for COPD in a 6-8 month clustered randomised controlled trial in Dutch general practices ( http://www.trialregister.nl : NTR4041). GPs allocated to microspirometry (MI) used COPD-6(r) microspirometers in patients >=50 years old with a smoking history and respiratory complaints that could indicate undiagnosed COPD and ask to refer patients for full spirometry if MI was positive (FEV1/FEV6 <0.73). Introduction of the COPD-6(r) was postponed in the usual care (UC) group. GPs of both study arms were asked to list all patients that fulfilled study criteria and at the end of the study we screened the electronic medical record system for number of patients that fulfilled study criteria and visited their GP within the study period. Main end point was a documented diagnostic conclusion of COPD within 3 months after the patient's visit. We used multilevel logistic regression with correction for relevant covariates. Next, we described the process of care. 21 practices (88 GPs) participated and 416 possible undiagnosed COPD patient visited these practices in the study period. 78 (of 192 visiting) subjects were listed by MI GPs and diagnostic conclusions were documented in 77%, compared to 61 listed (of 224 visiting) subjects and 44% with documented diagnostic conclusions by UC GPs (Odds Ratio: OR: 4.3, 95%CI: 1.6-11.5). Microspirometry improved the diagnostic process for possible underlying COPD in patients who consulted their GP with respiratory symptoms, but the majority of possible undiagnosed COPD patients remained unrecognised by GPs. PMID- 29789609 TI - Author Correction: A B-ARR-mediated cytokinin transcriptional network directs hormone cross-regulation and shoot development. AB - The original version of this Article contained an error in Fig. 3. Panel b was inadvertently duplicated and the correct panel c was originally omitted. This error has been corrected in both the PDF and HTML versions of the Article. PMID- 29789608 TI - Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells. AB - Individuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (EDNRB), and its ligand Endothelin1 (EDN1). Depletion of EDNRB mRNA in cord blood-derived CD34+ cells led to defective B cell differentiation, supporting a hypothesis that low EDNRB expression in T21 contributes to intrinsic lymphoid defects. Further evidence for the role of the EDNRB pathway in B cell differentiation was obtained through CRISPR/Cas9 gene targeting in disomic and trisomic iPS cells. Knockout of EDNRB in both cell backgrounds reduced the capacity for B cell differentiation. Collectively, this work identifies downregulation of EDNRB as a causative factor for impaired B lymphocyte generation in trisomic cells, which may contribute to defects in immune function associated with T21. Furthermore, a novel role for endothelin signaling in regulation of B cell development has been identified. PMID- 29789610 TI - On the scattering directionality of a dielectric particle dimer of High Refractive Index. AB - Low-losses and directionality effects exhibited by High Refractive Index Dielectric particles make them attractive for applications where radiation direction control is relevant. For instance, isolated metallo-dielectric core shell particles or aggregates (dimers) of High Refractive Index Dielectric particles have been proposed for building operational switching devices. Also, the possibility of using isolated High Refractive Index Dielectric particles for optimizing solar cells performance has been explored. Here, we present experimental evidence in the microwave range, that a High Refractive Index Dielectric dimer of spherical particles is more efficient for redirecting the incident radiation in the forward direction than the isolated case. In fact, we report two spectral regions in the dipolar spectral range where the incident intensity is mostly scattered in the forward direction. They correspond to the Zero-Backward condition (also observed for isolated particles) and to a new condition, denoted as "near Zero-Backward" condition, which comes from the interaction effects between the particles. The proposed configuration has implications in solar energy harvesting devices and in radiation guiding. PMID- 29789612 TI - Synthesis and insecticidal efficacy of pyripyropene derivatives focusing on the C 1, C-7, and C-11 positions' substituent groups. AB - The C-1, C-7, and C-11 positions of pyripyropene A were chemically modified to improve the insecticidal activity. Some derivatives showed higher insecticidal activities against aphids than pyripyropene A. In particular, the derivative 5c, which possesses three cyclopropyl carbonyl groups at the C-1, C-7, and C-11 positions, had excellent insecticidal activity levels in field and laboratory trials. PMID- 29789613 TI - Author Correction: Biochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions. AB - The original version of the Supplementary Information associated with this Article contained an error in Supplementary Figure 2 and Supplementary Figure 5 in which the 31P NMR spectral lines were missing. The HTML has been updated to include a corrected version of the Supplementary Information. PMID- 29789611 TI - An Intrinsic Role of Beta Oscillations in Memory for Time Estimation. AB - The neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals. PMID- 29789614 TI - Augmenting the Calvin-Benson-Bassham cycle by a synthetic malyl-CoA-glycerate carbon fixation pathway. AB - The Calvin-Benson-Bassham (CBB) cycle is presumably evolved for optimal synthesis of C3 sugars, but not for the production of C2 metabolite acetyl-CoA. The carbon loss in producing acetyl-CoA from decarboxylation of C3 sugar limits the maximum carbon yield of photosynthesis. Here we design a synthetic malyl-CoA-glycerate (MCG) pathway to augment the CBB cycle for efficient acetyl-CoA synthesis. This pathway converts a C3 metabolite to two acetyl-CoA by fixation of one additional CO2 equivalent, or assimilates glyoxylate, a photorespiration intermediate, to produce acetyl-CoA without net carbon loss. We first functionally demonstrate the design of the MCG pathway in vitro and in Escherichia coli. We then implement the pathway in a photosynthetic organism Synechococcus elongates PCC7942, and show that it increases the intracellular acetyl-CoA pool and enhances bicarbonate assimilation by roughly 2-fold. This work provides a strategy to improve carbon fixation efficiency in photosynthetic organisms. PMID- 29789615 TI - IL-37 isoform D downregulates pro-inflammatory cytokines expression in a Smad3 dependent manner. AB - IL-37 is a new member of IL-1 family and possesses five different isoforms (named as IL-37 a-e). IL-37b has been demonstrated as a physiological suppressor of immune responses. However, the function of other isoforms remains unknown. Here, we show that IL-37d possesses anti-inflammatory roles both in vitro and in vivo. Firstly, IL-37d is expressed in peripheral blood mononuclear cells (PBMCs) and umbilical cords-derived mesenchymal stem cells (UCMSCs). Secondly, IL-37d overexpression markedly inhibits IL-1beta-induced IL-6 production in A549 cells. Consistently, bone marrow-derived macrophages (BMDMs) from IL-37d transgenic mice express low levels of pro-inflammatory cytokines (such as IL-6 and TNF-alpha) following LPS stimulation, compared with those from wild-type mice. Furthermore, IL-37d transgenic mice produce less pro-inflammatory cytokines, and show much less degree of LPS-induced endotoxemia in vivo. Mechanistically, IL-37d interacts with Smad3 and promotes nuclear translocation of pSmad3. SIS3 (a specific Smad3 inhibitor) treatment completely blocks the inhibitory effects of IL-37d. Thus, our data indicate that IL-37d is a functional cytokine that negatively regulates pro-inflammatory cytokines expression in a Smad3-dependent manner. PMID- 29789617 TI - Functional analysis of eliciting plant response protein Epl1-Tas from Trichoderma asperellum ACCC30536. AB - Eliciting plant response protein (Epl) is a small Trichoderma secreted protein that acts as an elicitor to induce plant defense responses against pathogens. In the present study, the differential expression, promoter analysis, and phylogenetic tree analysis of Epl1-Tas (GenBank JN966996) from T. asperellum ACCC30536 were performed. The results showed Epl1-Tas could play an important role in the interaction between T. asperellum ACCC30536 and woody plant or woody plant pathogen. Furthermore, the effect of the Escherichia coli recombinant protein rEpl1-e and the Pichia pastoris recombinant protein rEpl1-p on Populus davidiana * P. alba var. pyramidalis (PdPap) was studied. In PdPap seedlings, rEpl1-e or rEpl1-p induction altered the expression levels of 11 genes in the salicylic acid (SA, three genes), jasmonic acid (JA, four genes) and auxin (four genes) signal transduction pathways, and five kinds of enzymes activities The induction level of rEpl1-p was significantly higher than that of rEpl1-e, indicating that rEpl1-p could be used for further induction experiment. Under 3 mg/mL rEpl1-p induction, the mean height of the PdPap seedlings increased by 57.65% and the mean lesion area on the PdPap seedlings leaves challenged with Alternaria alternata decreased by 91.22% compared with those of the control. Thus, elicitor Epl1-Tas could induce the woody plant resistance to pathogen. PMID- 29789618 TI - The Diversity of Chemoprotective Glucosinolates in Moringaceae (Moringa spp.). AB - Glucosinolates (GS) are metabolized to isothiocyanates that may enhance human healthspan by protecting against a variety of chronic diseases. Moringa oleifera, the drumstick tree, produces unique GS but little is known about GS variation within M. oleifera, and even less in the 12 other Moringa species, some of which are very rare. We assess leaf, seed, stem, and leaf gland exudate GS content of 12 of the 13 known Moringa species. We describe 2 previously unidentified GS as major components of 6 species, reporting on the presence of simple alkyl GS in 4 species, which are dominant in M. longituba. We document potent chemoprotective potential in 11 of 12 species, and measure the cytoprotective activity of 6 purified GS in several cell lines. Some of the unique GS rank with the most powerful known inducers of the phase 2 cytoprotective response. Although extracts of most species induced a robust phase 2 cytoprotective response in cultured cells, one was very low (M. longituba), and by far the highest was M. arborea, a very rare and poorly known species. Our results underscore the importance of Moringa as a chemoprotective resource and the need to survey and conserve its interspecific diversity. PMID- 29789616 TI - rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. AB - Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle cells. Furthermore, expression of rbFOX1 corrects alternative splicing alterations and rescues muscle atrophy, climbing and flying defects caused by expression of expanded CCUG repeats in a Drosophila model of DM2. PMID- 29789619 TI - A Predictive Spatial Distribution Framework for Filovirus-Infected Bats. AB - Tools with predictive capabilities in regards of filovirus outbreaks are mainly anthropocentric and have disregarded the ecological dimension of the problem. Here we contribute to shift the current paradigm by studying the dynamics of the putative main zoonotic niche of filoviruses, bats, and its link to environmental drivers. We propose a framework that combines data analysis, modeling, and the evaluation of sources of variability. We implement a regression analysis using factual data to correlate environmental parameters and the presence of bats to find the distribution of resources. The information inferred by the regression is fed into a compartmental model that describes the infection state. We also account for the lack of knowledge of some parameters using a sampling/averaging technique. As a result we estimate the spatio-temporal densities of bats. Importantly, we show that our approach is able to predict where and when an outbreak is likely to appear when tested against recent epidemic data in the context of Ebola. Our framework highlights the importance of considering the feedback between the ecology and the environment in zoonotic models and sheds light on the mechanisms to propagate filoviruses geographically. We expect that our methodology can help to design prevention policies and be used as a predictive tool in the context of zoonotic diseases associated to filoviruses. PMID- 29789620 TI - Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components. AB - Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here we determine a super-resolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we term the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164, which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs. PMID- 29789621 TI - Taxon-specific aerosolization of bacteria and viruses in an experimental ocean atmosphere mesocosm. AB - Ocean-derived, airborne microbes play important roles in Earth's climate system and human health, yet little is known about factors controlling their transfer from the ocean to the atmosphere. Here, we study microbiomes of isolated sea spray aerosol (SSA) collected in a unique ocean-atmosphere facility and demonstrate taxon-specific aerosolization of bacteria and viruses. These trends are conserved within taxonomic orders and classes, and temporal variation in aerosolization is similarly shared by related taxa. We observe enhanced transfer into SSA of Actinobacteria, certain Gammaproteobacteria, and lipid-enveloped viruses; conversely, Flavobacteriia, some Alphaproteobacteria, and Caudovirales are generally under-represented in SSA. Viruses do not transfer to SSA as efficiently as bacteria. The enrichment of mycolic acid-coated Corynebacteriales and lipid-enveloped viruses (inferred from genomic comparisons) suggests that hydrophobic properties increase transport to the sea surface and SSA. Our results identify taxa relevant to atmospheric processes and a framework to further elucidate aerosolization mechanisms influencing microbial and viral transport pathways. PMID- 29789622 TI - Molecule-based microelectromechanical sensors. AB - Incorporating functional molecules into sensor devices is an emerging area in molecular electronics that aims at exploiting the sensitivity of different molecules to their environment and turning it into an electrical signal. Among the emergent and integrated sensors, microelectromechanical systems (MEMS) are promising for their extreme sensitivity to mechanical events. However, to bring new functions to these devices, the functionalization of their surface with molecules is required. Herein, we present original electronic devices made of an organic microelectromechanical resonator functionalized with switchable magnetic molecules. The change of their mechanical properties and geometry induced by the switching of their magnetic state at a molecular level alters the device's dynamical behavior, resulting in a change of the resonance frequency. We demonstrate that these devices can be operated to sense light or thermal excitation. Moreover, thanks to the collective interaction of the switchable molecules, the device behaves as a non-volatile memory. Our results open up broad prospects of new flexible photo- and thermo-active hybrid devices for molecule based data storage and sensors. PMID- 29789625 TI - Clinical diagnosis of veno-occlusive disease using contrast enhanced ultrasound. PMID- 29789623 TI - MiR-29c reduces the cisplatin resistance of non-small cell lung cancer cells by negatively regulating the PI3K/Akt pathway. AB - In previous studies, miR-29s showed tumor suppressor properties against lung cancer, which improved the survival of patients upon the administration of chemotherapy via an unknown mechanism. Here, we investigated the regulatory effects of miR-29s on the cisplatin resistance of NSCLC cells. The expression of miR-29s was assessed in 130 clinical patients and in cisplatin-treated NSCLS cell lines. MiR-29c expression was decreased in 77% of NSCLC patients. Cisplatin treatment increased the expression of miR-29c and decreased the expression of its oncogenic target AKT2 in NSCLC cell lines. A Kaplan-Meier survival analysis indicated that higher miR-29c levels led to a longer disease-free survival. In particular, patients who experienced cancer recurrences after cisplatin chemotherapy exhibited a lower level of miR-29c expression, suggesting that miR 29c activation may contribute to the chemotherapeutic efficiency of cisplatin. The enforced expression of miR-29c enhanced the cisplatin sensitivity of NSCLC cells, while the knocking down of miR-29c led to cisplatin resistance. MiR-29c amplified the therapeutic effects of cisplatin in vivo. Rescue experiments suggested that miR-29c regulates the cisplatin resistance of NSCLS cells by negatively regulating the PI3K/Akt pathway. Overall, our results demonstrated that miR-29c enhances the sensitivity of NSCLC cells to cisplatin by targeting the PI3K/Akt pathway. PMID- 29789626 TI - Efficacy of cardiac contractility modulation confirmed. PMID- 29789624 TI - Interplay between gut microbiota metabolism and inflammation in HIV infection. AB - HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic analyses. The transcriptionally active microbiota was well-adapted to the inflamed environment, overexpressing pathways related to resistance to oxidative stress. Furthermore, gut inflammation was maintained by the Gram-negative nature of the HIV-associated microbiota and underexpression of anti-inflammatory processes, such as short chain fatty acid biosynthesis or indole production. We performed co-occurrence and metabolic network analyses that showed relevance in the microbiota structure of both taxonomic and metabolic HIV-associated biomarkers. The Bayesian network revealed the most determinant pathways for maintaining the structure stability of the bacterial community. In addition, we identified the taxa's contribution to metabolic activities and their interactions with host health. PMID- 29789627 TI - Publisher Correction: Exosome-based therapy to repair the injured heart. AB - The article originally published online contained an error in the figure in which the scale bar was incorrectly associated with a value of 100 um. This error has been corrected in the HTML and PDF versions of the article to associate the scale bar with the correct value of 1 mm. PMID- 29789629 TI - Non-coding RNAs in Various Stages of Liver Disease Leading to Hepatocellular Carcinoma: Differential Expression of miRNAs, piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. AB - Hepatocellular carcinoma (HCC) was the fifth leading cause of cancer death in men and eighth leading cause of death in women in the United States in 2017. In our study, we sought to identify sncRNAs in various stages of development of HCC. We obtained publicly available small RNA-seq data derived from patients with cirrhosis (n = 14), low-grade dysplastic nodules (LGDN, n = 9), high grade dysplastic nodules (HGDN, n = 6), early hepatocellular carcinoma (eHCC, n = 6), and advanced hepatocellular carcinoma (HCC, n = 20), along with healthy liver tissue samples (n = 9). All samples were analyzed for various types of non-coding RNAs using PartekFlow software. We remapped small RNA-seq to miRBase to obtain differential expressions of miRNAs and found 87 in cirrhosis, 106 in LGDN, 59 in HGDN, 80 in eHCC, and 133 in HCC. Pathway analysis of miRNAs obtained from diseased samples compared to normal samples showed signaling pathways in the microRNA dependent EMT, CD44, and others. Additionally, we analyzed the data sets for piRNAs, lncRNAs, circRNAs, and sno/mt-RNAs. We validated the in silico data using human HCC samples with NanoString miRNA global expression. Our results suggest that publically available data is a valuable resource for sncRNA identification in HCC progression (FDR set to <0.05 for all samples) and that a data mining approach is useful for biomarker development. PMID- 29789630 TI - Preclinical evaluation of ribociclib and its synergistic effect in combination with alpelisib in non-keratinizing nasopharyngeal carcinoma. AB - Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment. (IC50 concentrations: HK1 = 1.42 +/- 0.23 uM; HK1-LMP1 = 2.18 +/- 0.70 uM and C666-1 = 8.26 +/- 0.92 uM). HK1 and C666-1 cells were chosen for analysis of ribociclib on kinase signaling, apoptosis and cell cycle. Treatment with ribociclib for 48 hours consistently showed a dose-dependent reduction in phosphorylated and total RB expression and G1 cycle arrest was only observed. Combining ribociclib with the alpha-specific PI3K inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude mice. The co-treatment induced a significant reduction in tumor volume in both xeno-666 and xeno-2117 compared with ribociclib treatment alone and control (p < 0.01). In summary, ribociclib is active in NPC models and the effect on growth inhibition was augmented when combined with alpelisib. This study supports the clinical evaluation of ribociclib in NPC. PMID- 29789631 TI - Systematic evaluation of a 171Yb optical clock by synchronous comparison between two lattice systems. AB - Optical clocks are the most precise measurement devices. Here we experimentally characterize one such clock based on the 1S0-3P0 transition of neutral 171Yb atoms confined in an optical lattice. Given that the systematic evaluation using an interleaved stabilization scheme is unable to avoid noise from the clock laser, synchronous comparisons against a second 171Yb lattice system were implemented to accelerate the evaluation. The fractional instability of one clock falls below 4 * 10-17 after an averaging over a time of 5,000 seconds. The systematic frequency shifts were corrected with a total uncertainty of 1.7 * 10 16. The lattice polarizability shift currently contributes the largest source. This work paves the way to measuring the absolute clock transition frequency relative to the primary Cs standard or against the International System of Units (SI) second. PMID- 29789628 TI - Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models. AB - T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN 6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models. PMID- 29789633 TI - 3D Interconnected Binder-Free Electrospun MnO@C Nanofibers for Supercapacitor Devices. AB - Rational design of binder-free materials with high cyclic stability and high conductivity is a great need for high performance supercapacitors. We demonstrate a facile one-step synthesis method of binder-free MnO@C nanofibers as electrodes for supercapacitor applications. The topology of the fabricated nanofibers was investigated using FESEM and HRTEM. The X-ray photoelectron spectroscopy (XPS) and the X-ray diffraction (XRD) analyses confirm the formation of the MnO structure. The electrospun MnO@C electrodes achieve high specific capacitance of 578 F/g at 1 A/g with an outstanding cycling performance. The electrodes also show 127% capacity increasing after 3000 cycles. An asymmetric supercapacitor composed of activated carbon as the negative electrode and MnO@C as the positive electrode shows an ultrahigh energy density of 35.5 Wh/kg with a power density of 1000 W/kg. The device shows a superior columbic efficiency, cycle life, and capacity retention. PMID- 29789632 TI - The Developmental Process of the Growing Motile Ciliary Tip Region. AB - Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis. Our results demonstrated that the distal tip region of motile cilia exhibit progressive morphological changes as cilia develop. This developmental process is time dependent and continues after growing cilia reach their full lengths. The structural analysis of growing ciliary tips revealed that B-tubules of axonemal microtubule doublets terminate far away from the tip end, which is led by the flagellar tip complex (FTC), demonstrating that the FTC might not directly mediate the fast turnover of intraflagellar transport (IFT). PMID- 29789634 TI - Giant photovoltaic response in band engineered ferroelectric perovskite. AB - Recently the solar energy, an inevitable part of green energy source, has become a mandatory topics in frontier research areas. In this respect, non centrosymmetric ferroelectric perovskites with open circuit voltage (VOC) higher than the bandgap, gain tremendous importance as next generation photovoltaic materials. Here a non-toxic co-doped Ba1-x(Bi0.5Li0.5) x TiO3 ferroelectric system is designed where the dopants influence the band topology in order to enhance the photovoltaic effect. In particular, at the optimal doping concentration (x opt ~ 0.125) the sample reveals a remarkably high photogenerated field EOC = 320 V/cm (VOC = 16 V), highest ever reported in any bulk polycrystalline non-centrosymmetric systems. The band structure, examined through DFT calculations, suggests that the shift current mechanism is key to explain the large enhancement in photovoltaic effect in this family. PMID- 29789635 TI - Publisher Correction: Quantum engineering of transistors based on 2D materials heterostructures. AB - In the version of this Perspective originally published, in the email address for the author Giuseppe Iannaccone, the surname was incorrectly given as "innaconne"; this has now been corrected in all versions of the Perspective. Also, an error in the production process led to Figs. 1, 2 and 3 being of low resolution; these have now been replaced with higher-quality versions. PMID- 29789636 TI - Cypripedin diminishes an epithelial-to-mesenchymal transition in non-small cell lung cancer cells through suppression of Akt/GSK-3beta signalling. AB - Lung cancer appears to have the highest rate of mortality among cancers due to its metastasis capability. To achieve metastasis, cancer cells acquire the ability to undergo a switch from epithelial to mesenchymal behaviour, termed the epithelial-to-mesenchymal transition (EMT), which is associated with poor clinical outcomes. Drug discovery attempts have been made to find potent compounds that will suppress EMT. Cypripedin, a phenanthrenequinone isolated from Thai orchid, Dendrobium densiflorum, exhibits diverse pharmacological activities. In this study, we found that cypripedin attenuated typical mesenchymal phenotypes, including migratory behaviour, of non-small cell lung cancer H460 cells, with a significant reduction of actin stress fibres and focal adhesion and with weakened anchorage-independent growth. Western blot analysis revealed that the negative activity of this compound on EMT was a result of the down-regulation of the EMT markers Slug, N-Cadherin and Vimentin, which was due to ATP-dependent tyrosine kinase (Akt) inactivation. As a consequence, the increase in the Slug degradation rate via a ubiquitin-proteasomal mechanism was encouraged. The observation in another lung cancer H23 cell line also supported this finding, indicating that cypripedin exhibits a promising pharmacological action on lung cancer metastasis that could provide scientific evidence for the further development of this compound. PMID- 29789639 TI - Fludarabine and neurotoxicity in engineered T-cell therapy. AB - Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension. The lymphodepleting agent fludarabine was suggested as the causative agent, in part due to its known association with neurotoxicity and its ability to induce greater potency. In a similar CAR-T study also incorporating fludarabine in the preconditioning regimen, ZUMA-1 (NCT02348216), one patient died of cerebral edema. However, subsequent deaths in the JCAR-015 study after removal of fludarabine and improved understanding behind the mechanisms of CAR-T-related encephalopathy syndrome (CRES) indicate that fludarabine is not the primary causative agent of cerebral edema and that it can be safely incorporated into the preconditioning regimen for ACT. Since entering clinical use in the late 1980s as a chemotherapy agent, fludarabine and similar analogs have been associated with lethal neurological toxicity, yet the manifestation and timing of symptoms are distinct to those observed recently in ACT. Herein, we review the history of fludarabine development as a chemotherapeutic agent, and discuss the safety of its continued use in preconditioning regimens for ACT. PMID- 29789637 TI - The proton pump inhibitor pantoprazole disrupts protein degradation systems and sensitizes cancer cells to death under various stresses. AB - Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins. Notably, PPI-induced autophagy functioned as a downstream response of proteasome inhibition by PPI, while suppressing protein synthesis abrogated autophagy. Blocking autophagic flux in neutral pH condition or further impairing proteasome function with proteasome inhibitors, significantly aggravated PPI cytotoxicity by worsening protein degradation ability. Interestingly, under conditions of mitochondrial stress, PPI showed significant synergism when combined with Bcl-2 inhibitors. Taken together, these findings provide a new understanding of the impact of PPIs on cancer cells' biological processes and highlight the potential to develop more efficient and effective combination therapies. PMID- 29789641 TI - Diurnal blood pressure changes. AB - The definition of diurnal blood pressure changes varies widely, which can be confusing. Short-term blood pressure variability during a 24-h period and the dipping status of diurnal blood pressure can be captured by ambulatory blood pressure monitoring, and these metrics are reported to have prognostic significance for cardiovascular complications. Morning blood pressure surge also indicates this risk, but its effect may be limited to populations with specific conditions. Meanwhile, the combined use of conventional office blood pressure and out-of-office blood pressure allows us to identify people with white-coat and masked hypertension. Current home devices can measure nocturnal blood pressure during sleep more conveniently than ambulatory monitoring; however, we should pay attention to blood pressure measurement conditions regardless of whether they are in a home, ambulatory, or office setting. The relatively poor reproducibility of diurnal blood pressure changes, including the nocturnal fall of blood pressure, is another underestimated issue to be addressed. Although information on diurnal blood pressure changes is expected to be used more effectively in the future, we should also keep in mind that blood pressure levels have remained central to the primary and secondary prevention of blood pressure-related cardiovascular diseases in clinical practice. PMID- 29789638 TI - Human carbonic anhydrase-8 AAV8 gene therapy inhibits nerve growth factor signaling producing prolonged analgesia and anti-hyperalgesia in mice. AB - Carbonic anhydrase-8 (Car8; murine gene symbol) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates neuronal intracellular calcium release. We previously reported that wild-type Car8 overexpression corrects the baseline allodynia and hyperalgesia associated with calcium dysregulation in the waddle (wdl) mouse due to a 19 bp deletion in exon 8 of the Car8 gene. In this report, we provide preliminary evidence that overexpression of the human wild-type ortholog of Car8 (CA8WT), but not the reported CA8 S100P loss of-function mutation (CA8MT), inhibits nerve growth factor (NGF)-induced phosphorylation of ITPR1, TrkA (NGF high-affinity receptor), and ITPR1-mediated cytoplasmic free calcium release in vitro. In addition, we show that gene transfer using AAV8-V5-CA8WT viral particles via sciatic nerve injection demonstrates retrograde transport to dorsal root ganglia (DRG) producing prolonged V5-CA8WT expression, pITPR1 and pTrkA inhibition, and profound analgesia and anti-hyperalgesia in male C57BL/6J mice. AAV8-V5-CA8WT-mediated overexpression prevented and treated allodynia and hyperalgesia associated with chronic neuropathic pain produced by the spinal nerve ligation (SNL) model. These AAV8-V5-CA8 data provide a proof-of-concept for precision medicine through targeted gene therapy of NGF-responsive somatosensory neurons as a long-acting local analgesic able to prevent and treat chronic neuropathic pain through regulating TrkA signaling, ITPR1 activation, and intracellular free calcium release by ITPR1. PMID- 29789642 TI - Spatial and temporal variations of particulate organic carbon in the Yellow-Bohai Sea over 2002-2016. AB - The Yellow-Bohai Sea (YBS) is a typical marginal sea in the Northwest Pacific Ocean; however, little is known about the dynamics of particulate organic carbon (POC) and underlying mechanisms. Here, we analyze the spatial and temporal variations of surface POC derived from MODIS-Aqua during 2002-2016. Overall, POC is higher in the Bohai Sea (315-588 mg m-3) than in the Yellow Sea (181-492 mg m 3), and higher in the nearshore than in the offshore. Surface POC is highest in spring in the YBS, and lowest in winter (summer) in the Bohai Sea (the Yellow Sea). The spatial and seasonal patterns of POC are due to combined influences of primary productivity, water exchange, sediment resuspension and terrestrial inputs. Surface POC shows an overall decreasing trend prior to 2012 followed by an upward trend until 2015 in the YBS, which is almost opposite to chlorophyll; the decrease (increase) may result from strengthened (weakened) water exchange with the East China Sea through the Yellow Sea Warm Current. Declined terrestrial runoff is also partly responsible for the decrease prior to 2012. Our study suggests that water exchange and sediment resuspension are dominant factors regulating the spatial and temporal variability of POC in the YBS. PMID- 29789643 TI - Changes in pituitary gene expression may underlie multiple domesticated traits in chickens. AB - Domesticated animals share a unique set of morphological and behavioral traits, jointly referred to as the domesticated phenotype. Striking similarities amongst a range of unrelated domesticated species suggest that similar regulatory mechanisms may underlie the domesticated phenotype. These include color pattern, growth, reproduction, development and stress response. Although previous studies have focused on the brain to find mechanisms underlying domestication, the potential role of the pituitary gland as a target of domestication is highly overlooked. Here, we study gene expression in the pituitary gland of the domesticated White Leghorn chicken and its wild ancestor, the Red Junglefowl. By overlapping differentially expressed genes with a previously published list of functionally important genes in the pituitary gland, we narrowed down to 34 genes. Amongst them, expression levels of genes with inhibitory function on pigmentation (ASIP), main stimulators of metabolism and sexual maturity (TSHB and DIO2), and a potential inhibitor of broodiness (PRLR), were higher in the domesticated breed. Additionally, expression of 2 key inhibitors of the stress response (NR3C1, CRHR2) was higher in the domesticated breed. We suggest that changes in the transcription of important modulatory genes in the pituitary gland can account not only for domestication of the stress response in domestic chickens, but also for changes in pigmentation, development, and reproduction. Given the pivotal role of the pituitary gland in the regulation of multiple shared domesticated traits, we suggest that similar changes in pituitary transcriptome may contribute to the domesticated phenotype in other species as well. PMID- 29789640 TI - Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-beta load: A pilot study. AB - The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer's disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-beta load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90 y, were categorised into NAL+ (n = 35) and NAL- (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEepsilon4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL- participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/- as outcome were carried out. After age and APOEepsilon4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEepsilon4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis. PMID- 29789644 TI - Heritability of climate-relevant traits in a rainforest skink. AB - There is justified concern about the impact of global warming on the persistence of tropical ectotherms. There is also growing evidence for strong selection on climate-relevant physiological traits. Understanding the evolutionary potential of populations is especially important for low dispersal organisms in isolated populations, because these populations have little choice but to adapt. Despite this, direct estimates of heritability and genetic correlations for physiological traits in ectotherms-which will determine their evolutionary responses to selection-are sparse, especially for reptiles. Here we examine the heritabilities and genetic correlations for a set of four morphological and six climate-relevant physiological traits in an isolated population of an Australian rainforest lizard, Lampropholis coggeri. These traits show considerable variation across populations in this species, suggesting local adaptation. From laboratory crosses, we estimated very low to moderate heritability of temperature-related physiological traits (h2 < 0.31), but significant and higher heritability of desiccation resistance (h2~0.42). These values contrasted with uniformly higher heritabilities (h2 > 0.51) for morphological traits. At the phenotypic level, there were positive associations among the morphological traits and between thermal limits. Growth rate was positively correlated with thermal limits, but there was no indication that morphology and physiology were linked in any other way. We found some support for a specialist-generalist trade-off in the thermal performance curve, but otherwise there was no evidence for evolutionary constraints, suggesting broadly labile multivariate trait structure. Our results indicate little potential to respond to selection on thermal traits in this population and provide new insights into the capacity of tropical ectotherms to adapt in situ to rapid climate change. PMID- 29789645 TI - Author Correction: Balance between Estrogens and Proinflammatory Cytokines Regulates Chemokine Production Involved in Thymic Germinal Center Formation. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29789646 TI - Age-related differences in limb fat-free mass and fat mass in healthy Chinese Adults. AB - Fat mass (FM) and fat-free mass (FFM) are important elements to evaluate nutritional status. The aims of this study were to establish reference values for FM and FFM of limbs, develop percentile distributions and assess age-related regional differences in body composition by multifrequency bioelectrical impedance analyzer (BIA) in healthy adults. A cross-sectional study was conducted on 3419 healthy subjects, 1595 men and 1824 women. Regional FM and FFM were measured by BIA. FM in men remained stable in both upper and lower limbs, with reference values (25-75th percentile) of 1-1.5 kg and 4.9-7.2 kg, respectively. Women's leg FM remained stable with aging (reference values 6.2-7.9 kg), increasing in their arms (0.9-1.5 kg for youngest, 1.3-2.3 kg oldest). The reference values of upper limbs FFM were 5.3-6.2 kg in men and 3.3-3.9 kg in women. Lower limbs FFM decreased with age in both gender: the reference values were 19.5-23.3 kg (men) and 13.8-15.4 kg (women) for 18-30 age group, and 17.3-20 kg and 11.2-13.1 kg, respectively, for 60+ age group. These data provided reference values of FM and FFM in both limbs, enabling the identification of age and gender-related changes in limb composition in healthy Chinese subjects. PMID- 29789648 TI - DALM, rest in peace: a pathologist's perspective on dysplasia in inflammatory bowel disease in the post-DALM era. AB - There are few abbreviations in surgical pathology that are associated with as much immediate recognition, frustration, and confusion as DALM (dysplasia associated lesion or mass). DALM is used to describe endoscopically visible dysplastic lesions in the surveillance of patients with inflammatory bowel disease. However, the diagnosis of DALM has been complicated by the inconsistent criteria and use of terminology for describing dysplasia in inflammatory bowel disease, and a tendency to relate DALM with the need for colectomy. Fortunately, advancements in both endoscopic visualization and local excision capability have allowed for a more defined management of dysplasia in inflammatory bowel disease. In 2015, the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients International Consensus Recommendations (SCENIC) Development Panel, a panel of predominantly expert gastroenterologists and endoscopists in surveillance of inflammatory bowel disease, published a consensus statement. One recommendation was to abandon DALM related terminology in favor of endoscopic descriptors modified from the Paris endoscopic classification. Recommendations on surveillance and management of dysplastic lesions were also provided. Nevertheless, interval carcinomas and metachronous neoplasia remain persistent issues. This review aims to provide an update on the post-DALM terminology and management recommendations for inflammatory bowel disease-associated dysplasia necessary for a meaningful communication between pathologists and clinicians. PMID- 29789647 TI - Microbial production of novel sulphated alkaloids for drug discovery. AB - Natural products from plants are useful as lead compounds in drug discovery. Plant benzylisoquinoline alkaloids (BIAs) exhibit various pharmaceutical activities. Although unidentified BIAs are expected to be of medicinal value, sufficient quantities of such BIAs, for biological assays, are sometimes difficult to obtain due to their low content in natural sources. Here, we showed that high productivity of BIAs in engineered Escherichia coli could be exploited for drug discovery. First, we improved upon the previous microbial production system producing (S)-reticuline, an important BIA intermediate, to obtain yields of around 160 mg/L, which was 4-fold higher than those of the previously reported highest production system. Subsequently, we synthesised non-natural BIAs (O sulphated (S)-reticulines) by introducing human sulphotransferases into the improved (S)-reticuline production system. Analysis of human primary cells treated with these BIAs demonstrated that they affected a biomarker expression in a manner different from that by the parent compound (S)-reticuline, suggesting that simple side-chain modification altered the characteristic traits of BIA. These results indicated that highly productive microbial systems might facilitate the production of scarce or novel BIAs and enable subsequent evaluation of their biological activities. The system developed here could be applied to other rare natural products and might contribute to the drug-discovery process as a next generation strategy. PMID- 29789649 TI - Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion. AB - We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with the presence of WNT pathway gene alterations, all superficially serrated adenomas showed focal or diffuse nuclear beta-catenin accumulation. Since concurrent KRAS mutations and RSPO fusions are reportedly common in traditional serrated adenomas, we reviewed 129 traditional serrated adenomas and found 15 lesions (12%) that were associated with superficially serrated adenoma components. Remarkably, all but one superficially serrated adenoma-associated traditional serrated adenoma exhibited concurrent KRAS mutations and RSPO fusions/overexpression. The present study suggests that superficially serrated adenoma is a morphologically and molecularly distinct type of colorectal serrated polyp that is histogenetically related to traditional serrated adenoma. PMID- 29789650 TI - Use of DNA flow cytometry in the diagnosis, risk stratification, and management of gastric epithelial dysplasia. AB - The natural history of gastric epithelial dysplasia and the consequential surveillance strategies are not well defined in the West. To date, the diagnosis relies on morphology, and no reliable adjunct methods, either immunohistochemical or molecular, have reproducibly been able to confirm the diagnosis and/or risk stratify gastric epithelial dysplasia. Yet, such a tool would be useful in confirming the diagnosis, and developing objective and rational surveillance guidelines. DNA flow cytometry was performed using formalin-fixed paraffin embedded gastric tissue from 23 cases of high-grade dysplasia and 38 cases of low grade dysplasia. Twenty-four benign background mucosal samples from the same cohort (20 biopsies and 4 surgical resections from 16 low- and 8 high-grade dysplasia cases) were utilized as controls. The presence of DNA content abnormality (aneuploidy or elevated 4N fraction) correlated with increasing levels of dysplasia, as DNA content abnormality was detected in 18 (78%) of 23 high-grade dysplasia, 5 (13%) of 38 low-grade dysplasia, and none of 24 non dysplastic samples. 1 and 4-year detection rates of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 80% (p = 0.003) and 100% (p = 0.005), respectively, whereas patients with low-grade dysplasia but with normal DNA content had 1, 4, and 12 year detection rates of 23, 32, and 54%, respectively. The univariate hazard ratio (HR) for subsequent detection of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality was 6.9 (p = 0.001). Older patients (HR = 1.1, p = 0.005) and those with familial adenomatous polyposis (HR = 9.7, p = 0.029) also had an increased risk for developing high-grade dysplasia or gastric adenocarcinoma in the univariate analysis, but only DNA content abnormality demonstrated a significantly elevated HR of 5.9 in the multivariate analysis (p = 0.005). While older age showed a minimally elevated risk (HR = 1.1, p = 0.013), no other potential risk factors, including male gender, ethnicity, polypoid endoscopic appearance, Helicobacter pylori infection, and intestinal metaplasia, were significantly associated with subsequent detection of high-grade dysplasia or gastric adenocarcinoma in the multivariate analysis. Among the 18 high-grade dysplasia cases with DNA content abnormality, 13 cases (72%) developed gastric adenocarcinoma within a mean follow up time of 9 months, conferring a HR of 2.5; however, this did not reach statistical significance. In conclusion, the presence of DNA content abnormality can identify a subset of low-grade dysplasia patients who are at increased risk for subsequent detection of high-grade dysplasia or gastric adenocarcinoma. It can also provide confirmatory evidence to a morphologic impression or suspicion of high-grade dysplasia. The majority of gastric epithelial dysplasia patients with DNA content abnormality developed high-grade dysplasia or gastric adenocarcinoma within a year and thus may benefit from more thorough and rigorous endoscopic surveillance. PMID- 29789651 TI - Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. AB - In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication. PMID- 29789652 TI - Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease. AB - Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naive cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naive MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD. PMID- 29789653 TI - Ring quantum cascade lasers with twisted wavefronts. AB - We demonstrate the on-chip generation of twisted light beams from ring quantum cascade lasers. A monolithic gradient index metamaterial is fabricated directly into the substrate side of the semiconductor chip and induces a twist of the light's wavefront. This significantly influences the obtained beam pattern, which changes from a central intensity minimum to a maximum depending on the discontinuity count of the metamaterial. Our design principle provides an interesting alternative to recent implementations of microlasers operating at an exceptional point. PMID- 29789654 TI - Direct observation of pitting corrosion evolutions on carbon steel surfaces at the nano-to-micro- scales. AB - The Cl--induced corrosion of metals and alloys is of relevance to a wide range of engineered materials, structures, and systems. Because of the challenges in studying pitting corrosion in a quantitative and statistically significant manner, its kinetics remain poorly understood. Herein, by direct, nano- to micro scale observations using vertical scanning interferometry (VSI), we examine the temporal evolution of pitting corrosion on AISI 1045 carbon steel over large surface areas in Cl--free, and Cl--enriched solutions. Special focus is paid to examine the nucleation and growth of pits, and the associated formation of roughened regions on steel surfaces. By statistical analysis of hundreds of individual pits, three stages of pitting corrosion, namely, induction, propagation, and saturation, are quantitatively distinguished. By quantifying the kinetics of these processes, we contextualize our current understanding of electrochemical corrosion within a framework that considers spatial dynamics and morphology evolutions. In the presence of Cl- ions, corrosion is highly accelerated due to multiple autocatalytic factors including destabilization of protective surface oxide films and preservation of aggressive microenvironments within the pits, both of which promote continued pit nucleation and growth. These findings offer new insights into predicting and modeling steel corrosion processes in mid-pH aqueous environments. PMID- 29789655 TI - Cigarette smoke promotes HIV infection of primary bronchial epithelium and additively suppresses CFTR function. AB - Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway. In our earlier work, we have demonstrated that bronchial epithelium expresses canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. HIV Tat suppresses CFTR mRNA and function via TGF-beta signaling. In the present study, we demonstrate that cigarette smoke (CS) potentiates HIV infection of bronchial epithelial cells by upregulating CD4 and CCR5 expression. HIV and CS individually and additively suppress CFTR biogenesis and function, possibly explaining the increased incidence of lung infections in HIV patients and its exacerbation in HIV smokers. PMID- 29789656 TI - Distribution of different surface modified carbon dots in pumpkin seedlings. AB - The distribution of surface modified carbon dots (CDs) in the pumpkin seedlings was studied by visualization techniques and their potential phytotoxicity was investigated at both the physiological and biochemical levels. The average size of carbon dots was approximately 4 nm. The fluorescent peaks of bared CDs, CD-PEI and CD-PAA were between 420 nm and 500 nm, indicating CDs could emit blue and green fluorescence. Fluorescent images showed that all three types of CDs could accumulate in the pumpkin roots and translocate to the shoots, although the distribution pattern of each CDs was obviously different. At the biochemical level, the elevated antioxidant enzymes in pumpkin roots suggest that all the CDs could potentially trigger the antioxidant defense systems in pumpkin seedlings. Additionally, such alteration was greater in the roots than in the shoots. Our study represents a new perspective on CD visualization in plant tissues and provide useful information for the potential toxicity of different types of CDs to terrestrial plants, which is of importance to agricultural application. PMID- 29789658 TI - Comment on 'Overprescribing of antibiotics by UK ophthalmologists'. PMID- 29789657 TI - The COOH-terminal domain of huntingtin interacts with RhoGEF kalirin and modulates cell survival. AB - Human huntingtin (Htt) contains 3144 amino acids and has an expanded polyglutamine region near the NH2-terminus in patients with Huntington's disease. While numerous binding partners have been identified to NH2-terminal Htt, fewer proteins are known to interact with C-terminal domains of Htt. Here we report that kalirin, a Rac1 activator, is a binding partner to C-terminal Htt. Kalirin and Htt co-precipitated from mouse brain endosomes and co-localized at puncta in NRK and immortalized striatal cells and primary cortical neurons. We mapped the interaction domains to kalirin674-1272 and Htt2568-3144 and determined that the interaction between kalirin and Htt was independent of HAP1, a known interactor for Htt and kalirin. Kalirin precipitated with mutant Htt was more abundant than with wild-type Htt and had a reduced capacity to activate Rac1 when mutant Htt was present. Expression of Htt2568-3144 caused cytotoxicity, partially rescued by co-expressing kalirin674-1272 but not other regions of kalirin. Our study suggests that the interaction of kalirin with the C-terminal region of Htt influences the function of kalirin and modulates the cytotoxicity induced by C terminal Htt. PMID- 29789659 TI - Comparison of glaucoma-diagnostic ability between wide-field swept-source OCT retinal nerve fiber layer maps and spectral-domain OCT. AB - PURPOSE: To compare the diagnostic ability of wide-field swept-source optical coherence tomography (SS-OCT) retinal nerve fiber layer (RNFL) maps with spectral domain OCT (SD-OCT) maps for detection of preperimetric (PPG) and early glaucoma (EG). PATIENTS AND METHODS: One hundred and forty-six eyes, including 37 healthy eyes, 38 eyes with PPG, and 71 eyes with EG, were analyzed. The patients underwent both SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA, USA) and wide-field SS-OCT scanning (DRI-OCT-1 Atlantis; Topcon, Tokyo, Japan). By SD-OCT, circumpapillary RNFL and macular ganglion cell analyses were performed. SS-OCT provides a wide-field RNFL thickness map and a SuperPixel map, which are composed of an RNFL deviation map of the peripapillary area and a deviation map of the composition of the ganglion cell layer with the inner plexiform layer and RNFL [GC-IPL+RNFL] in the macular area. The ability to discriminate PPG and EG from healthy eyes was assessed according to sensitivity, specificity and area under the receiver operating characteristic curve for parameters and criteria provided by SD-OCT and wide-field SS-OCT scanning. RESULTS: The wide-field RNFL thickness map obtained by SS-OCT showed the highest sensitivity to PPG and EG (92.1 and 97.2%, respectively) as compared with the other, SD-OCT criteria. The wide-field RNFL thickness map showed PPG-diagnostic performance comparable to the SD-OCT RNFL thickness and GC-IPL deviation maps (p = 0.453 and 0.180), and PPG diagnostic performance superior to the SD-OCT RNFL deviation and GC-IPL thickness maps (p = 0.003 and 0.039). In EG, the wide-field RNFL thickness and SuperPixel maps showed diagnostic performance comparable to the SD-OCT thickness and deviation maps (p = 0.065 to 0.100), except for the GC-IPL thickness map (p = 0.004). CONCLUSIONS: The wide-field SS-OCT RNFL thickness maps showed a diagnostic ability for distinguishing PPG and EG from healthy eyes that was similar to that of SD-OCT. In the clinical setting, these maps can be effective for detection of early-glaucomatous changes. PMID- 29789660 TI - MultiColorTM imaging in combined hamartoma of the retina and retinal pigment epithelium. AB - PURPOSE: To describe the principle characteristics of combined hamartoma of the retina and retinal pigment epithelium ('combined harmatoma') on MultiColorTM imaging and evaluate its role as a diagnostic and management tool. METHODS: Retrospective, observational case series comprising three patients with unilateral, juxtapapillary combined harmatoma. Complete ophthalmic examination was performed. MultiColorTM, including green reflectance (GR) and near infra-red reflectance (NIRR), optical coherence tomography (OCT) and autofluorescence (AF) imaging were obtained (Heidelberg Spectralis). RESULTS: On MultiColorTM, 'red shifting', indicated partial pigmentation. GR clearly defined epiretinal gliosis, retinal dragging and striations. On NIRR, all lesions were hypo-reflectant with hyper-reflectance at their edges. OCT showed full-thickness retinal thickening and disorganisation, intra-retinal fluid in two cases, sectoral RPE atrophy with photoreceptor loss in one case, RPE thickening and foveal pigment migration in one case; epiretinal membrane associated with 'mini peaks' of the inner retina in all cases and vitreous traction causing retinoschisis in one case. All lesions were hypo-autofluorescent. CONCLUSIONS: MultiColorTM enables combined harmatomas to be further characterised and may represent a valuable diagnostic and management tool: MultiColorTM and NIR define tumour boundaries and macular involvement, which may be useful for assessing visual impact; GR highlights inner retinal distortion, which may aid surgical management decisions. PMID- 29789661 TI - A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses. AB - Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+ T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+ T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells. PMID- 29789662 TI - Spraying dynamics in continuous wave laser printing of conductive inks. AB - Laser-induced forward transfer (LIFT), though usually associated with pulsed lasers, has been recently shown to be feasible for printing liquid inks with continuous wave (CW) lasers. This is remarkable not only because of the advantages that the new approach presents in terms of cost, but also because of the surprising transfer dynamics associated with it. In this work we carry out a study of CW-LIFT aimed at understanding the new transfer dynamics and its correlation with the printing outcomes. The CW-LIFT of lines of Ag ink at different laser powers and scan speeds revealed a range of conditions that allowed printing conductive lines with good electrical properties. A fast-imaging study showed that liquid ejection corresponds to a spraying behavior completely different from the jetting characteristic of pulsed LIFT. We attribute the spray to pool-boiling in the donor film, in which bursting bubbles are responsible for liquid ejection in the form of projected droplets. The droplet motion is then modeled as the free fall of rigid spheres in a viscous medium, in good agreement with experimental observations. Finally, thermo-capillary flow in the donor film allows understanding the evolution of the morphology of the printed lines with laser power and scan speed. PMID- 29789664 TI - The BET bromodomain inhibitor apabetalone induces apoptosis of latent HIV-1 reservoir cells following viral reactivation. AB - The persistence of latent HIV-1 reservoirs throughout combination antiretroviral therapy (cART) is a major barrier on the path to achieving a cure for AIDS. It has been shown that bromodomain and extra-terminal (BET) inhibitors could reactivate HIV-1 latency, but restrained from clinical application due to their toxicity and side effects. Thus, identifying a new type of BET inhibitor with high degrees of selectivity and safety is urgently needed. Apabetalone is a small molecule selective BET inhibitor specific for second bromodomains, and has been evaluated in phase III clinical trials that enrolled patients with high-risk cardiovascular disorders, dyslipidemia, and low HDL cholesterol. In the current study, we examined the impact of apabetalone on HIV-1 latency. We showed that apabetalone (10-50 MUmol/L) dose-dependently reactivated latent HIV-1 in 4 types of HIV-1 latency cells in vitro and in primary human CD4+ T cells ex vivo. In ACH2 cells, we further demonstrated that apabetalone activated latent HIV-1 through Tat-dependent P-TEFB pathway, i.e., dissociating bromodomain 4 (BDR4) from the HIV-1 promoter and recruiting Tat for stimulating HIV-1 elongation. Furthermore, we showed that apabetalone (10-30 MUmol/L) caused dose-dependent cell cycle arrest at the G1/G0 phase in ACH2 cells, and thereby induced the preferential apoptosis of HIV-1 latent cells to promote the death of reactivated reservoir cells. Notably, cardiovascular diseases and low HDL cholesterol are known as the major side effects of cART, which should be prevented by apabetalone. In conclusion, apabetalone should be an ideal bifunctional latency reversing agent for advancing HIV-1 eradication and reducing the side effects of BET inhibitors. PMID- 29789665 TI - Existing and novel biomarkers for precision medicine in systemic sclerosis. AB - The discovery and validation of biomarkers resulting from technological advances in the analysis of genomic, transcriptomic, lipidomic and metabolomic pathways involved in the pathogenesis of complex human diseases have led to the development of personalized and rationally designed approaches for the clinical management of such disorders. Although some of these approaches have been applied to systemic sclerosis (SSc), an unmet need remains for validated, non-invasive biomarkers to aid in the diagnosis of SSc, as well as in the assessment of disease progression and response to therapeutic interventions. Advances in global transcriptomic technology over the past 15 years have enabled the assessment of microRNAs that circulate in the blood of patients and the analysis of the macromolecular content of a diverse group of lipid bilayer membrane-enclosed extracellular vesicles, such as exosomes and other microvesicles, which are released by all cells into the extracellular space and circulation. Such advances have provided new opportunities for the discovery of biomarkers in SSc that could potentially be used to improve the design and evaluation of clinical trials and that will undoubtedly enable the development of personalized and individualized medicine for patients with SSc. PMID- 29789663 TI - Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage. AB - The original PDF version of this Article listed the authors as "Marcus J.G.W. Ladds," where it should have read "Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#".Also in the PDF version, it was incorrectly stated that "Correspondence and requests for materials should be addressed to S. Lin.", instead of the correct "Correspondence and requests for materials should be addressed to S. Lain."This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication. PMID- 29789667 TI - Imputation of missing values in a large job exposure matrix using hierarchical information. AB - Job exposure matrices (JEMs) represent a useful and efficient approach for estimating occupational exposures. This study uses a large dataset of full-shift measurements and employs imputation strategies to develop noise exposure estimates for almost all broad level standard occupational classification (SOC) groups in the US. The JEM was constructed using 753,702 measurements from the government, private industry, and the published literature. Parametric Bayes imputation was used to take advantage of the hierarchical structure of the SOCs and the mean occupational noise exposures were estimated for all broad level SOCs, except those in major group 23-0000, for which no data were available. The estimated posterior mean for all broad SOCs was found to be 82.1 dBA with within- and between-major SOC variabilities of 22.1 and 13.8, respectively. Of the 443 broad SOCs, 85 were found to have an estimated mean exposure >85 dBA while 10 were >90 dBA. By taking advantage of the size and structure of the dataset, we were able to employ imputation techniques to estimate mean levels of noise exposure for nearly all SOCs in the US. Possible sources of errors in the estimates include misclassification of job titles due to limited data, temporal variations that were not accounted for, and variation in exposures within the same SOC. Our efforts have resulted in an almost completely populated noise JEM that provides a valuable tool for the assessment of occupational exposures to noise. Imputation techniques can lead to maximal use of available information that may be incomplete. PMID- 29789669 TI - Consumer behaviour survey for assessing exposure from consumer products: a feasibility study. AB - Evaluating chemical exposures from consumer products is an essential part of chemical safety assessments under REACH and may also be important to demonstrate compliance with consumer product legislation. Modelling of consumer exposure needs input information on the substance (e.g. vapour pressure), the product(s) containing the substance (e.g. concentration) and on consumer behaviour (e.g. use frequency and amount of product used). This feasibility study in Germany investigated methods for conducting a consumer survey in order to identify and retrieve information on frequency, duration, use amounts and use conditions for six example product types (four mixtures, two articles): hand dishwashing liquid, cockpit spray, fillers, paints and lacquers, shoes made of rubber or plastic, and ball-pens/pencils. Retrospective questionnaire methods (Consumer Product Questionnaire (CPQ), and Recall-Foresight Questionnaire (RFQ)) as well as protocol methods (written reporting by participants and video documentation) were used. A combination of retrospective questionnaire and written protocol methods was identified to provide valid information in a resource-efficient way. Relevant information, which can readily be used in exposure modelling, was obtained for all parameters and product types investigated. Based on the observations in this feasibility study, recommendations are given for designing a large consumer survey. PMID- 29789666 TI - Cross-plane coherent acoustic phonons in two-dimensional organic-inorganic hybrid perovskites. AB - Two-dimensional Ruddlesden-Popper organic-inorganic hybrid layered perovskites (2D RPs) are solution-grown semiconductors with prospective applications in next generation optoelectronics. The heat-carrying, low-energy acoustic phonons, which are important for heat management of 2D RP-based devices, have remained unexplored. Here we report on the generation and propagation of coherent longitudinal acoustic phonons along the cross-plane direction of 2D RPs, following separate characterizations of below-bandgap refractive indices. Through experiments on single crystals of systematically varied perovskite layer thickness, we demonstrate significant reduction in both group velocity and propagation length of acoustic phonons in 2D RPs as compared to the three dimensional methylammonium lead iodide counterpart. As borne out by a minimal coarse-grained model, these vibrational properties arise from a large acoustic impedance mismatch between the alternating layers of perovskite sheets and bulky organic cations. Our results inform on thermal transport in highly impedance mismatched crystal sub-lattices and provide insights towards design of materials that exhibit highly anisotropic thermal dissipation properties. PMID- 29789668 TI - Sources of household air pollution and their association with fine particulate matter in low-income urban homes in India. AB - INTRODUCTION: Household air pollution (HAP) is poorly characterized in low-income urban Indian communities. MATERIALS AND METHODS: A questionnaire assessing sources of HAP and 24 h household concentrations of particulate matter less than 2.5 microns in diameter (PM2.5) were collected in a sample of low-income homes in Pune, India. RESULTS: In 166 homes, the median 24 h average concentration of PM2.5 was 167 MUg/m3 (IQR: 106-294). Although kerosene and wood use were highly prevalent (22% and 25% of homes, respectively), primarily as secondary fuel sources, high PM2.5 concentrations were also found in 95 (57%) homes reporting LPG use alone (mean 141 MUg/m3; IQR: 92-209). In adjusted linear regression, log PM2.5 concentration was positively associated with wood cooking fuel (GMR 1.5, 95% CI: 1.1-2.0), mosquito coils (GMR 1.5, 95% CI: 1.1-2.1), and winter season (GMR 1.7, 95% CI: 1.4-2.2). Households in the highest quartile of exposure were positively associated with wood cooking fuel (OR 1.3, 95% CI: 1.1-1.5), incense (OR 1.1, 95% CI: 1.0-1.3), mosquito coils (OR 1.3, 95% CI: 1.1-1.6), and winter season (OR 1.2, 95% CI: 1.1-1.4). DISCUSSION: We observed high concentrations of PM2.5 and identified associated determinants in urban Indian homes. PMID- 29789670 TI - Noise estimation model development using high-resolution transportation and land use regression. AB - Noise pollution is a common phenomenon of the 21st century. Noise prediction models tend to estimate noise levels mainly from road traffic sources (such as cars, public transportation etc.). This paper describes the adoption of land use regression (LUR) modeling methodology to assess noise pollution in two periods of the day (rush hour and off-peak), in two major cities in Israel (Tel Aviv and Beer Sheva). For both rush hour and off-peak times, 20 min short term measurements were used to develop a LUR noise estimation model. We used GIS-based predictors alongside commonly used traffic predictors. The findings show good fits for our model, with rush hour "out of sample" ten folds cross-validated R2 of 0.79 (Tel Aviv) and 0.52 (Beer Sheva). The Tel Aviv model performance was also tested with independent monitoring data in an adjacent city (Bat Yam), presenting a good performance as well (R2 of 0.93). The findings demonstrate the viability of using a LUR approach for applying high-resolution spatial data to estimate and map noise pollution for environmental noise assessment. PMID- 29789671 TI - Wild and domesticated Moringa oleifera differ in taste, glucosinolate composition, and antioxidant potential, but not myrosinase activity or protein content. AB - Taste drives consumption of foods. The tropical tree Moringa oleifera is grown worldwide as a protein-rich leafy vegetable and for the medicinal value of its phytochemicals, in particular its glucosinolates, which can lead to a pronounced harsh taste. All studies to date have examined only cultivated, domestic variants, meaning that potentially useful variation in wild type plants has been overlooked. We examine whether domesticated and wild type M. oleifera differ in myrosinase or glucosinolate levels, and whether these different levels impact taste in ways that could affect consumption. We assessed taste and measured levels of protein, glucosinolate, myrosinase content, and direct antioxidant activity of the leaves of 36 M. oleifera accessions grown in a common garden. Taste tests readily highlighted differences between wild type and domesticated M. oleifera. There were differences in direct antioxidant potential, but not in myrosinase activity or protein quantity. However, these two populations were readily separated based solely upon their proportions of the two predominant glucosinolates (glucomoringin and glucosoonjnain). This study demonstrates substantial variation in glucosinolate composition within M. oleifera. The domestication of M. oleifera appears to have involved increases in levels of glucomoringin and substantial reduction of glucosoonjnain, with marked changes in taste. PMID- 29789673 TI - Peatland vegetation composition and phenology drive the seasonal trajectory of maximum gross primary production. AB - Gross primary production (GPP) is a key driver of the peatland carbon cycle. Although many studies have explored the apparent GPP under natural light conditions, knowledge of the maximum GPP at light-saturation (GPPmax) and its spatio-temporal variation is limited. This information, however, is crucial since GPPmax essentially constrains the upper boundary for apparent GPP. Using chamber measurements combined with an external light source across experimental plots where vegetation composition was altered through long-term (20-year) nitrogen addition and artificial warming, we could quantify GPPmax in-situ and disentangle its biotic and abiotic controls in a boreal peatland. We found large spatial and temporal variations in the magnitudes of GPPmax which were related to vegetation species composition and phenology rather than abiotic factors. Specifically, we identified vegetation phenology as the main driver of the seasonal GPPmax trajectory. Abiotic anomalies (i.e. in air temperature and water table level), however, caused species-specific divergence between the trajectories of GPPmax and plant development. Our study demonstrates that photosynthetically active biomass constrains the potential peatland photosynthesis while abiotic factors act as secondary modifiers. This further calls for a better representation of species-specific vegetation phenology in process-based peatland models to improve predictions of global change impacts on the peatland carbon cycle. PMID- 29789672 TI - Comparison of Fast-Track Versus Conventional Surgery Protocol for Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy: A Chinese Experience. AB - Fast-track surgery (FTS), which includes a series of evidence-based adjustments, is expected to reduce complications, relieve surgical stress reaction, accelerate recovery, and shorten hospitalization, as well as improve safety. The aim of this study was to critically evaluate the safety and effectiveness of FTS in Chinese prostate cancer (Pca) patients who underwent robot-assisted laparoscopic prostatectomy (RALP). A retrospective analysis was performed on 73 consecutive Chinese Pca patients who underwent RALP and who were divided into two groups: conventional surgery (CS) and FTS. Preoperative clinical data, intraoperative characteristics, postoperative outcomes and incidence of complications were compared between the two groups. No significant differences in preoperative parameters were observed between the two groups. Compared with the CS group, the FTS group showed a significantly shorter time to first flatus, time to regular diet, postoperative hospitalization time, lower incidence of complications, and lower reactions of postoperative stress and pain. Our study demonstrates that FTS is feasible and safe for Chinese Pca patients undergoing RALP and that it accelerates recovery, attenuates surgical stress response, and reduces morbidity compared to CS. PMID- 29789674 TI - Tuning Alginate-Gelatin Bioink Properties by Varying Solvent and Their Impact on Stem Cell Behavior. AB - Bioink optimization is considered as one of main challenges in cell-laden 3D bioprinting. Alginate-Gelatin (Alg-Gel) hydrogel have been extensively used as bioink. However, its properties could be influenced by various parameters, and little is known about the evidence featuring the impact of solvent. Here we investigated four Alg-Gel bioink by varying solvent ionic strength (named B-1, B 2, B-3 and B-4). Mechanical properties and printability of bioink samples and their impacts on behaviors of encapsulated epidermal stem cells (ESCs) were tested. Bioink with increased ionic strength of solvent showed decreased stiffness and viscosity, and increased swelling and degradation by printability and mechanical property tests. Due to the increased swelling and degradation was associated with shape-maintenance of post-printing constructs, B-3 and B-4 were hardly observable after 14 days. Cellular behaviors were assessed through viability, proliferation, aggregation and differentiation tests. B-2 with optimal properties resulted in higher viability and proliferation of ESCs, and further facilitated cellular aggregation and lineage differentiation. We demonstrated that the solvent can be tuned by ionic strength to control the properties of Alg Gel bioink and post-printing constructs, which represented a promising avenue for promotion of therapeutic stem cell behaviors in 3D bioprinting. PMID- 29789675 TI - Publisher Correction: Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29789676 TI - The angiotensin-I-converting enzyme insertion/deletion in polymorphic element codes for an AluYa5 RNA that downregulates gene expression. AB - Angiotensin-I-converting enzyme (ACE) is involved in the synthesis and degradation of important bioactive peptides. The ACE gene has a 287-bp insertion/deletion polymorphism that controls ACE expression through a mechanism that remains elusive. In this study, we found that the 287-bp polymorphic element of the ACE gene, a member of the AluYa5 sub-family of Alu elements, codes for an RNA molecule that controls the levels of ACE mRNA. Transient transfection of a plasmid containing a CMV promoter upstream of the ACE polymorphic element resulted in significant expression of an AluYa5 RNA and reduced ACE mRNA expression as well as ACE enzymatic activity in AD 293 cells. The AluYa5 element also independently reduced the expression of other genes, regardless of whether these genes harbored Alu elements within their genomic context. Interestingly, the CMV promoter was not required for the expression of the AluYa5 element in AD 293 cells. The 287-bp sequence was sufficient to produce AluYa5 RNA and led to a significant reduction in ACE gene expression. Moreover, the removal of an 11-bp fragment of the 3' end of the ACE polymorphic sequence, which is specific to this particular AluYa5 element, did not prevent this element from being expressed but did affect its ability to target ACE expression. Thus, the expression of the AluYa5 polymorphic element within the ACE gene could explain why patients carrying the ACE insertion polymorphism have reduced risk of developing several chronic diseases. PMID- 29789677 TI - Taking on the intractable. PMID- 29789678 TI - Dealing with the pain. PMID- 29789679 TI - Live cables over long distances. PMID- 29789680 TI - Keystone taxa as drivers of microbiome structure and functioning. AB - Microorganisms have a pivotal role in the functioning of ecosystems. Recent studies have shown that microbial communities harbour keystone taxa, which drive community composition and function irrespective of their abundance. In this Opinion article, we propose a definition of keystone taxa in microbial ecology and summarize over 200 microbial keystone taxa that have been identified in soil, plant and marine ecosystems, as well as in the human microbiome. We explore the importance of keystone taxa and keystone guilds for microbiome structure and functioning and discuss the factors that determine their distribution and activities. PMID- 29789681 TI - Genomic and ecological study of two distinctive freshwater bacteriophages infecting a Comamonadaceae bacterium. AB - Bacteriophages of freshwater environments have not been well studied despite their numerical dominance and ecological importance. Currently, very few phages have been isolated for many abundant freshwater bacterial groups, especially for the family Comamonadaceae that is found ubiquitously in freshwater habitats. In this study, we report two novel phages, P26059A and P26059B, that were isolated from Lake Soyang in South Korea, and lytically infected bacterial strain IMCC26059, a member of the family Comamonadaceae. Morphological observations revealed that phages P26059A and P26059B belonged to the family Siphoviridae and Podoviridae, respectively. Of 12 bacterial strains tested, the two phages infected strain IMCC26059 only, showing a very narrow host range. The genomes of the two phages were different in length and highly distinct from each other with little sequence similarity. A comparison of the phage genome sequences and freshwater viral metagenomes showed that the phage populations represented by P26059A and P26059B exist in the environment with different distribution patterns. Presence of the phages in Lake Soyang and Lake Michigan also indicated a consistent lytic infection of the Comamonadaceae bacterium, which might control the population size of this bacterial group. Taken together, although the two phages shared a host strain, they showed completely distinctive characteristics from each other in morphological, genomic, and ecological analyses. Considering the abundance of the family Comamonadaceae in freshwater habitats and the rarity of phage isolates infecting this family, the two phages and their genomes in this study would be valuable resources for freshwater virus research. PMID- 29789682 TI - The role of diet in the aetiopathogenesis of inflammatory bowel disease. AB - Crohn's disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene-environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions. PMID- 29789683 TI - BMP-2 restoration aids in recovery from liver fibrosis by attenuating TGF-beta1 signaling. AB - Transforming growth factor-beta (TGF-beta) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP 2 and TGF-beta1. Hepatic BMP-2 was localized in parenchymal hepatocytes and activated HSCs and significantly decreased in human and mouse fibrotic livers, showing an opposite pattern of hepatic TGF-beta1 contents. BMP-2 gene delivery alleviated the elevations of serum hepatic enzymes, cholangiocyte marker CK19, HSC activation markers, and liver fibrosis in both models. Mechanistically, exogenous TGF-beta1 dose dependently reduced BMP-2 expression, whereas BMP-2 significantly suppressed expression of TGF-beta and its cognate type I and II receptor peptides, as well as the induced Smad3 phosphorylation levels in primary mouse HSCs. Aside from its suppressive effects on cell proliferation and migration, BMP-2 treatment prominently attenuated the TGF-beta1-stimulated alpha SMA and fibronectin expression, and reversed the TGF-beta1-modulated epithelial to-mesenchymal transition marker expression in mouse HSCs. The mutual regulation between BMP-2 and TGF-beta1 signaling axes may constitute the anti-fibrogenic mechanism of BMP-2 in the pathogenesis of liver fibrosis. BMP-2 may potentially serve as a novel therapeutic target for treatment of liver fibrosis. PMID- 29789684 TI - Dipeptidyl peptidase IV (DPP-4) inhibition alleviates pulmonary arterial remodeling in experimental pulmonary hypertension. AB - Dipeptidyl peptidase IV (DPP-4) is well known for its role in glucose homeostasis, and DPP-4 inhibitor (DPP-4i) exhibits multiple actions in cardiovascular diseases. However, the effect of DPP-4i on pulmonary hypertension (PH) remains unclear. Therefore, this study aims to investigate the effect of DPP 4i on pulmonary arterial remodeling in rats with PH and the potential underlying mechanisms. Our results show that DPP-4 was expressed in epithelial cells, endothelial cells, smooth muscle cells, and inflammatory cells in lung. DPP-4i (Sitagliptin) attenuated right ventricular systolic pressure (RVSP), right ventricle remodeling, hypertrophy of pulmonary arterial medial layer, inflammatory cell infiltration, and endothelial-mesenchymal transition (EndMT) in monocrotaline (MCT)-induced PH rats. Similarly, DPP-4i also alleviated bleomycin- and chronic hypoxia-induced PH in rats. In cultured human pulmonary arterial smooth muscle cells (PASMCs), DPP-4i inhibited platelet derived growth factor (PDGF)-BB-induced proliferation and migration, which was abolished by phosphatase and tensin homolog deleted on chromosome ten (PTEN) knockout. These results demonstrate that DPP-4 inhibition alleviates pulmonary arterial remodeling in experimental PH by inhibiting proliferation and migration of PASMCs. PMID- 29789685 TI - S100A4 protects mice from high-fat diet-induced obesity and inflammation. AB - As a member from S100 calcium-binding protein family, S100A4 is ubiquitous and elevated in tumor progression and metastasis, but its role in regulating obesity has not been well characterized. In this study, we showed that S100A4 was mainly expressed by stromal cells in adipose tissue and the S100A4 level in adipose tissue was decreased after high-fat diet (HFD). S100A4 deficient mice exhibited aggravated symptoms of obesity and suppressed insulin signaling after 12 weeks of HFD. Aggravated obesity in S100A4 deficient mice were found to be positively correlated with higher inflammatory status of the liver. Then, we found that extracellular S100A4 or overexpressed S100A4 inhibited adipogenesis and decreased mRNA levels of inflammation gene in 3T3-L1 adipocytes in vitro; whereas small interfering RNA (siRNA)-mediated suppression of S100A4 displayed the opposite results. Additionally, the protective effect induced by S100A4 during HFD-induced obesity was tightly related with activation of Akt signaling in adipose tissues, as well as livers and muscles. Taken together, we demonstrate that S100A4 is an inhibitory factor for obesity and attenuates the inflammatory reaction, while activating the Akt signaling, which suggest that S100A4 is a potential candidate for the treatment of diet-induced obesity and its complications. PMID- 29789686 TI - The personal and clinical utility of polygenic risk scores. AB - Initial expectations for genome-wide association studies were high, as such studies promised to rapidly transform personalized medicine with individualized disease risk predictions, prevention strategies and treatments. Early findings, however, revealed a more complex genetic architecture than was anticipated for most common diseases - complexity that seemed to limit the immediate utility of these findings. As a result, the practice of utilizing the DNA of an individual to predict disease has been judged to provide little to no useful information. Nevertheless, recent efforts have begun to demonstrate the utility of polygenic risk profiling to identify groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to disease. In this context, we review the evidence supporting the personal and clinical utility of polygenic risk profiling. PMID- 29789687 TI - First-line genomic diagnosis of mitochondrial disorders. PMID- 29789688 TI - Rapid Authentication of Ginkgo biloba Herbal Products Using the Recombinase Polymerase Amplification Assay. AB - Species adulteration in herbal products (HPs) exposes consumers to health risks. Chemical and morphological methods have their own deficiencies when dealing with the detection of species containing the same active compounds in HPs. In this study, we developed a rapid identification method using the recombinase polymerase amplification (RPA) assay to detect two species, Ginkgo biloba and Sophora japonica (as adulteration), in Ginkgo biloba HPs. Among 36 Ginkgo biloba HP samples, 34 were found to have Ginkgo biloba sequences, and 9 were found to have Sophora japonica sequences. During the authentication process, the RPA-LFS assay showed a higher specificity, sensitivity and efficiency than PCR-based methods. We initially applied the RPA-LSF technique to detect plant species in HPs, demonstrating that this assay can be developed into an efficient tool for the rapid on-site authentication of plant species in Ginkgo biloba HPs. PMID- 29789689 TI - Postmenopausal osteoporosis is associated with elevated aldosterone/renin ratio. AB - Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25 Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 +/- 78.8 vs. 81.8 +/- 71.5 pg/ml, p < 0.01 and 121.0 +/- 78.8 vs. 91.7 +/- 56.2 pg/ml, p < 0.01) and ARR (32.0 +/- 53.6 vs. 9.0 +/- 9.3 pg/MUU, p < 0.01 and 32.0 +/- 53.6 vs. 16.3 +/- 32.1 pg/MUU, p < 0.01) compared to women with normal BMD and osteopenia, respectively. Using ARR >= 37.0 pg/MUU as the cutoff for positive screening, more false-positive was found in the PMO group when compared to the normal BMD group (24 vs. 2%) and osteopenia group (24 vs. 7%), respectively. PAC was negatively associated with lumbar spine BMD T-score (r = -0.239, p < 0.001), femur neck BMD T-score (r = 0.234, p < 0.001) and total hip BMD T-score (r = -0.228, p < 0.001). PTH was positively associated with PAC (r = 0.119, p < 0.05) and ARR (r = 0.136, p < 0.05). PAC and ARR are elevated in women with PMO, which might increase the risk of false-positive for case detection of PA. PMID- 29789690 TI - Health-promoting behaviors and quality of life in older adults with hypertension as compared to a community control group. AB - Hypertension (HTN) related to health-promoting behaviors (HPB) and quality of life (QOL) in older Chinese has not been clearly identified. We sought to compare the HPB and QOL of elderly adults (aged >=60) living with HTN in China to a community normotensive control group. Using multistage stratified cluster sampling, a sample of 543 elderly people with HTN and 550 with normotension were randomly selected and asked to complete questionnaires. The Chinese version of the Health Promoting Lifestyle Profile (HPLP-IICR) and The World Health Organization Quality of life-BREF instrument (WHOQOL-BREF) were used to evaluate the HPB and QOL of elderly adults. As compared to the normotensive elderly, the hypertensive elderly showed significantly lower scores in their spiritual growth and health management (both P < 0.05), but not in the other three domains. Also, the participants with HTN showed significantly lower scores in the QOL overall and physical health (both P < 0.05), but not in other factors, as compared to the participants without HTN. Each HPLP-IICR domain score among the elderly with or without HTN were significantly correlated with their QOL scores (all P < 0.01). It is suggested that more attention should be paid to improving the spiritual growth and health management of HBP, and thus the overall quality of life among hypertensive patients. PMID- 29789691 TI - Performance of NoSAS score versus Berlin questionnaire for screening obstructive sleep apnoea in patients with resistant hypertension. AB - Obstructive sleep apnoea (OSA) is the main secondary form associated with resistant hypertension (RH), but it is largely underdiagnosed and consequently undertreated in clinical practice. The Berlin questionnaire (BQ) is a useful tool among general population, but seems to not perform well among patients with RH. Recently, NoSAS score was validated in a large population, however, has not been tested in the cardiovascular scenario. Thus, we aimed to compare BQ versus the NoSAS score as screening tools for OSA in RH. In the present study, patients with confirmed diagnosis of RH were invited to perform polysomnography. OSA was diagnosed by an apnoea-hypopnoea index (AHI) >=15 events/h. BQ and NoSAS were applied in a blinded way. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the two sleep questionnaires to detect OSA in RH. The frequency of OSA was 64%. The BQ presented a better sensitivity (91 vs. 72%) and higher values of NPV (67 vs. 54%) than NoSAS score. In contrast, the NoSAS score had higher specificity for excluding OSA (58 vs. 33%) and higher PPV (75 vs. 70%). Compared to the BQ, NoSAS score had a better AUC (0.55 vs. 0.64) but these values are in the fail to poor accuracy range. In conclusion, both BQ and NoSAS score had low accuracy for detecting OSA in RH. Considering the high frequency of OSA, objective sleep study may be considered in these patients. PMID- 29789694 TI - Watch and learn. PMID- 29789693 TI - Keeping track of time. PMID- 29789695 TI - Getting in on the action (potential). PMID- 29789692 TI - Pulse pressure amplification and cardiac autonomic dysfunction in patients with type 2 diabetes mellitus. AB - The main aim of this cross-sectional study was to investigate the association between pulse pressure amplification (PPA) and cardiac autonomic activity (baroreflex sensitivity (BRS) and heart rate variability (HRV)) in patients with type 2 diabetes mellitus (T2DM). In addition, we examined the association between cardiac autonomic activity and central hemodynamic parameters that may affect PPA such as augmentation index (AIx), aortic stiffness (pulse wave velocity (PWV)), and common carotid artery stiffness distensibility coefficient (DC). A total of 142 patients with T2DM were included in the study. In multivariate linear regression analysis-after controlling for age, diabetes duration, height, waist circumference, aortic PWV, use of beta-blockers, and BRS-PPA was associated significantly and independently with male gender (standardized regression coefficient (beta) = 0.156, p = 0.007), aortic systolic blood pressure (beta = 0.221, p < 0.001), heart rate (beta = 0.521, p < 0.001), AIotax (beta = -0.443, p < 0.001), and parameters of HRV, such as total power of HRV (beta = -0.157, p = 0.005). No significant associations were found between BRS or parameters of HRV with aortic PWV, AIx, or DC. In patients with T2DM, cardiac autonomic dysfunction was associated with enhanced PPA. This association was independent from the well described effect of resting heart rate, as well as from traditional cardiovascular risk factors or diabetes-related factors. Moreover, it was not mediated by effects of the autonomic dysfunction on arterial stiffness or on pressure wave reflections. These findings suggest that cardiac autonomic dysfunction affects PPA by mechanisms other than resting tachycardia and arterial properties. PMID- 29789697 TI - Setting the pace. PMID- 29789696 TI - Lifting spirits. PMID- 29789698 TI - Secondary findings in exome slices, virtual panels, and anticipatory sequencing. PMID- 29789699 TI - Genomics reveals distinct gastric cancer subtypes. PMID- 29789700 TI - Novel molecular classifications of DLBCL. PMID- 29789701 TI - Neoadjuvant FOLFIRINOX improves outcomes. PMID- 29789703 TI - Renal IL-17 activity in candidiasis. PMID- 29789704 TI - Single-cell RNA sequencing for the study of development, physiology and disease. AB - An ongoing technological revolution is continually improving our ability to carry out very high-resolution studies of gene expression patterns. Current technology enables the global gene expression profiles of single cells to be defined, facilitating dissection of heterogeneity in cell populations that was previously hidden. In contrast to gene expression studies that use bulk RNA samples and provide only a virtual average of the diverse constituent cells, single-cell studies enable the molecular distinction of all cell types within a complex population mix, such as a tumour or developing organ. For instance, single-cell gene expression profiling has contributed to improved understanding of how histologically identical, adjacent cells make different differentiation decisions during development. Beyond development, single-cell gene expression studies have enabled the characteristics of previously known cell types to be more fully defined and facilitated the identification of novel categories of cells, contributing to improvements in our understanding of both normal and disease related physiological processes and leading to the identification of new treatment approaches. Although limitations remain to be overcome, technology for the analysis of single-cell gene expression patterns is improving rapidly and beginning to provide a detailed atlas of the gene expression patterns of all cell types in the human body. PMID- 29789705 TI - The short-term effect of ultrasound and peripheral nerve stimulator-guided femoral nerve block with phenol on the outcomes of patients with traumatic spinal cord injury. AB - STUDY DESIGN: A pre-post descriptive study. OBJECTIVES: To examine the immediate effects of ultrasound-guided femoral nerve block with phenol (UGFNBwP) in managing the lower limb spasticity of individuals with traumatic spinal cord injury (SCI). SETTING: Ankara, Turkey. METHODS: Nineteen patients with traumatic SCI presenting with lower extremity spasticity were treated with UGFNBwP. Modified Ashworth Scale of hip flexion and knee extension, functional independence measure motor subscale, difficulty of catheterization, hygiene score, spasm frequency, sleep quality, and patient satisfaction (PS) were measured in all patients prior to treatment, in the first week and second month. RESULTS: There was a statistically significant decrease in the Modified Ashworth Scale scores in the first week and second month compared to baseline (p < 0.017). Significant improvements were detected in functional independence measure motor subscale, DoC, HS, SF and PS at follow-up examinations compared to baseline (p < 0.017). No statistically significant difference in the SQ score was found. Patients reported no complications during the intervention and follow-up period. CONCLUSIONS: Ultrasound-guided femoral nerve block with phenol is an option worth considering to reduce spasticity and improve function in people with SCI. PMID- 29789702 TI - Parallel descending dopaminergic connectivity of A13 cells to the brainstem locomotor centers. AB - The mesencephalic locomotor region (MLR) is an important integrative area for the initiation and modulation of locomotion. Recently it has been realized that dopamine (DA) projections from the substantia nigra pars compacta project to the MLR. Here we explore DA projections from an area of the medial zona incerta (ZI) known for its role in motor control onto the MLR. We provide evidence that dopaminergic (DAergic) A13 neurons have connectivity to the cuneiform nucleus (CnF) and pedunculopontine tegmental nucleus (PPTg) of the MLR. No ascending connectivity to the dorsolateral striatum was observed. On the other hand, DAergic A13 projections to the medullary reticular formation (MRF) and the lumbar spinal cord were sparse. A small number of non-DAergic neurons within the medial ZI projected to the lumbar spinal cord. We then characterized the DA A13 cells and report that these cells differ from canonical DA neurons since they lack the Dopamine Transporter (DAT). The lack of DAT expression, and possibly the lack of a dopamine reuptake mechanism, points to a longer time of action compared to typical dopamine neurons. Collectively our data suggest a parallel descending DAergic pathway from the A13 neurons of the medial ZI to the MLR, which we expect is important for modulating movement. PMID- 29789706 TI - Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders. AB - STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: The aim was to determine the frequency and magnetic resonance imaging (MRI) features of short segment transverse myelitis (STM) in patients with neuromyelitis optica spectrum disorders (NMOSD) during a myelitis attack. SETTING: Latin American diagnostic centres (Neuroimmunology Unit). A multicenter study from Argentina, Brazil and Venezuela was performed. METHODS: Seventy-six patients with NMOSD were included. We analyzed 346 attacks and reviewed spinal cord MRIs performed within 30 days from spinal attack onset. Sagittal and axial characteristics on cervical and thoracic MRI (1.5 tesla) were observed. Demographics, clinical, serological, and disability data were collected. RESULTS: Among the 76 patients with NMOSD, isolated STM was observed in 8% (n = 6), multisegmental lesions (longitudinally extensive transverse myelitis (LETM) + STM) in 28% (n = 21; 13 had at least one STM), LETM in 42% (n = 32), and normal spinal MRI in 22% (n = 17). However, isolated STM was increased by 10% in patients with NMOSD with spinal lesions (6 out of 59) with mean attacks of 2.5 (+/-0.83) and last follow-up expanded disability status scale (EDSS) of 3.1 (+/-2.63). Positive aquaporin 4 antibodies (AQP4-ab) were found in 50%. Upper-cervical lesion was most frequently observed (5 out of 6). Myelitis was preceded by ON in all isolated patients with STM. Only one had a positive gadolinium lesion and none of these had asymptomatic spinal cord lesion. CONCLUSION: Isolated STM does not exclude NMOSD diagnosis. Therefore, APQ4-ab testing could be useful during a myelitis attack with STM. PMID- 29789707 TI - The natural course of passive tenodesis grip in individuals with spinal cord injury with preserved wrist extension power but paralyzed fingers and thumbs. AB - STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate the natural course of passive tenodesis grip in individuals with spinal cord injury (SCI) with no experience of tenodesis splint application and the related factors for success of the grip. SETTING: Community-dwelling persons with chronic SCI in South Korea. METHODS: Individuals with cervical SCI with preserved wrist extensor power, but completely paralyzed fingers and thumbs, were recruited. For each hand, success or failure of passive tenodesis lateral grip was assessed both in the opening and closing phase. The key task in the Graded and Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) test was also assessed. RESULTS: Fifty-eight hands of 37 individuals with SCI were analyzed. In 35 of the 58 hands, both opening and closing phases of the grip were achieved. During the closing phase of the passive tenodesis lateral grip, the mean (s.d.) value of the second MP joint flexion angle ( degrees ) in the success group was 55.1 (13.6), compared to 38.6 (17.8) in the failure group. The key task in GRASSP was completed in only 14 out of 58 hands. Hands with a wrist extensor power of grade 4 or 5 on a manual muscle test showed higher GRASSP scores than those with a grade 3 wrist extensor power. CONCLUSIONS: The passive tenodesis lateral grip can be achieved in a large number of hands without splint application after SCI, but its use in the key task of the GRASSP is limited. PMID- 29789709 TI - Consumption of green tea but not coffee is associated with the oral health related quality of life among an older Japanese population: Kyoto-Kameoka cross sectional study. AB - BACKGROUND/OBJECTIVES: The consumption of both green tea and coffee is known to induce positive health effects; however, it remains unclear whether there is an association between the consumption of these beverages and oral health-related quality of life (OHRQoL). Thus, the present study investigated the relationship between the consumption of green tea and coffee and OHRQoL. SUBJECTS/METHODS: We analyzed cross-sectional baseline data in 2012. The subjects were 7514 Japanese participants (3563 men, 3951 women; >=65 years of age). Each subject completed a validated self-administered questionnaire that included items on the frequency of the consumption of green tea and coffee. OHRQoL was evaluated using the self reported General Oral Health Assessment Index (GOHAI), which assesses oral health problems in older adults. A GOHAI score <50 points was defined as a poor OHRQoL. RESULTS: Following adjustment for age, body mass index, total energy intake, alcohol, smoking, medication use, coffee, and fruit and vegetable consumption, increased consumption of green tea showed a strong positive association with the GOHAI score in both men and women (Ptrend < 0.001 in both). In contrast, after adjusting for all factors, no statistically significant association was observed between coffee consumption and the GOHAI score in men (Ptrend = 0.538) or women (Ptrend = 0.607). The respective multivariate-odds ratios (95% confidence intervals) for a poor OHRQoL associated with green tea consumption frequencies of none, <1 cup/day, 1-2 cups/day, and >=3 cups/day were 1.00, 1.01 (0.80-1.27), 0.95 (0.74-1.21), and 0.78 (0.61-0.99) (Ptrend = 0.024) in men, and 1.00, 1.19 (0.90-1.57), 0.98 (0.74-1.29), and 0.86 (0.67-1.12) (Ptrend = 0.014) in women. CONCLUSIONS: Regardless of sex, green tea consumption was positively associated with the GOHAI score. Therefore, >=3 cups/day of green tea may reduce the risk of a poor OHRQoL, especially in men. PMID- 29789708 TI - Combined genotyping, microbial diversity and metabolite profiling studies on farmed Mytilus spp. from Kiel Fjord. AB - The blue mussel Mytilus is a popular food source with high economical value. Species of the M. edulis complex (M. edulis, M. galloprovincialis and M. trossulus) hybridise whenever their geographic ranges overlap posing difficulties to species discrimination, which is important for blue mussel aquaculture. The aim of this study was to determine the genetic structure of farmed blue mussels in Kiel Fjord. Microbial and metabolic profile patterns were studied to investigate a possible dependency on the genotype of the bivalves. Genotyping confirmed the complex genetic structure of the Baltic Sea hybrid zone and revealed an unexpected dominance of M. trossulus alleles being in contrast to the predominance of M. edulis alleles described for wild Baltic blue mussels. Culture dependent and -independent microbial community analyses indicated the presence of a diverse Mytilus-associated microbiota, while an LC-MS/MS-based metabolome study identified 76 major compounds dominated by pigments, alkaloids and polyketides in the whole tissue extracts. Analysis of mussel microbiota and metabolome did not indicate genotypic dependence, but demonstrated high intraspecific variability of farmed mussel individuals. We hypothesise that individual differences in microbial and metabolite patterns may be caused by high individual plasticity and might be enhanced by e.g. nutritional condition, age and gender. PMID- 29789710 TI - Is misreporting of dietary intake by weighed food records or 24-hour recalls food specific? AB - BACKGROUND/OBJECTIVES: Healthy eating advice is informed, in part, by dietary surveys that rely on self-reported data. Misreporting of food intake may distort relationships between diet and health outcomes. This study directly quantified the food groups that were under-reported or over-reported in common dietary assessment techniques. SUBJECTS/METHODS: Food and drink consumption of 59 adults, with ad libitum access to a range of familiar foods, was objectively and covertly measured by investigators, and validated against independent measures of energy balance, while participants were resident in the Human Nutrition Unit of the Rowett Institute. Participants self-reported their diets using weighed dietary records (WDR) and multiple-pass 24-hr recalls over two periods of 3 days using a cross-over design. Foods and drinks were aggregated into 41 food groups. RESULTS: The mean daily weight of food and drinks reported was significantly lower than actually consumed; 3.3 kg (p = 0.004, 95% confidence interval (CI) = 3.07-3.55 kg) and 3.0 kg (p < 0.001, CI = 2.80-3.15 kg) for the WDR and 24-hr recall respectively, compared with 3.6 kg for the objective measure. Reported intakes were significantly lower than the objective measure for four and eight food groups (WDR and 24 h recall, respectively), and not significantly different for the remaining food groups. CONCLUSIONS: Although under-reporting was greater for some food groups than for others, 'healthy' foods were not over-reported and 'unhealthy' foods were not consistently under-reported. A better understanding of which foods tend to be misreported could lead to improvements in the methods of self-reported dietary intakes. PMID- 29789711 TI - Physical activity but not sedentary time is associated with vitamin D status in adolescents: study of cardiovascular risk in adolescents (ERICA). AB - BACKGROUND/OBJECTIVES: The association between active lifestyle components and vitamin D status in adolescents remains relatively unexplored. We aimed to investigate independent and joint associations of moderate-to-vigorous physical activity (MVPA) and screen time with serum 25-hydroxyvitamin D [25(OH)D] concentrations in adolescents. METHODS: This multicenter cross-sectional study involved 1152 Brazilian adolescents (age 12-17 years). Serum 25(OH)D was measured in a single laboratory and categorized as <=20, 21-29, or >=30 ng/mL. Demographic and lifestyle characteristics were assessed by self-reports. Ordered logistic regression was used to investigate potential associations of being physically active (MVPA >= 300 min/week) and excessive screen time (>2 h/day) with serum 25(OH)D concentrations. RESULTS: The prevalence of higher serum 25(OH)D concentrations (>=30 ng/mL) was 36.4%. In adjusted models, being physically active was associated with higher serum 25(OH)D concentrations only in boys [proportional odds ratio (POR) = 2.04, 95% CI 1.42-2.93], while excessive screen time was not associated with serum 25(OH)D. Adolescents who were physically active and limited their screen time had higher odds of a higher serum 25(OH)D concentration, but the association was significant only for boys (POR = 2.11, 95% CI 1.19-3.74). CONCLUSIONS: MVPA may play an important role in increasing serum 25(OH)D concentrations in adolescence, especially for boys, regardless of screen time. PMID- 29789712 TI - Distribution and determinants of retinol in Norwegian adolescents, and its relation to bone mineral density: the Tromso Study: Fit Futures. AB - BACKGROUND/OBJECTIVES: Sufficient vitamin A levels are important for many functions-and both too little and too much may have detrimental health effects. The aim of the study was to describe the distribution of retinol levels in Norwegian adolescents, the relation between lifestyle factors and retinol levels, and the relation between retinol levels and bone mineral density (BMD). SUBJECTS/METHODS: Serum retinol was measured in 414 girls and 474 boys aged 15-19 years, participating in the Tromso Study: Fit Futures. Questionnaires regarding health and lifestyle factors were filled in, and physical examinations, body composition, and bone mineral density measurements (DEXA) performed. Multiple regression analyses were used to discover associations between retinol and exposure variables. RESULTS: Retinol levels ranged from 0.26 to 6.46 MUmol/L with a median (2.5-97.5 percentile) of 2.35 (1.01-4.67) MUmol/L. There was no gender difference. In the multivariate models, fat mass, albumin level, physical activity, and lunch habits were positively associated with retinol levels in boys. In girls, fat mass and height were negatively associated with retinol levels, and lean mass, vitamin D, calcium, total cholesterol, and the use of contraceptives were positively associated with retinol levels (p < 0.05). The models explained 18.3% and 14.6% of the variation (R2) in girls and boys, respectively. Retinol levels were not independently associated with BMD. CONCLUSION: Retinol levels in Norwegian adolescents are higher than reported elsewhere, and are to a low degree explained by lifestyle and physical measurements. No independent association with BMD was found. PMID- 29789713 TI - Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer. AB - Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression. Loss of FOXD2-AS1 function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1 expression promoted cancer progression. The enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins were found to serve as binding partners of FOXD2-AS1 and mediators of FOXD2-AS1 function. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. PMID- 29789714 TI - Estrogen receptor beta promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network. AB - Recent studies indicated that the estrogen receptor beta (ERbeta) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERbeta expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERbeta with ERbeta-shRNA and stimulating the transactivation of ERbeta with 17beta-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERbeta-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERbeta-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future. PMID- 29789715 TI - Shared and independent functions of aPKClambda and Par3 in skin tumorigenesis. AB - The polarity proteins Par3 and aPKC are key regulators of processes altered in cancer. Par3/aPKC are thought to dynamically interact with Par6 but increasing evidence suggests that aPKC and Par3 also exert complex-independent functions. Whereas aPKClambda serves as tumor promotor, Par3 can either promote or suppress tumorigenesis. Here we asked whether and how Par3 and aPKClambda genetically interact to control two-stage skin carcinogenesis. Epidermal loss of Par3, aPKClambda, or both, strongly reduced tumor multiplicity and increased latency but inhibited invasion to similar extents, indicating that Par3 and aPKClambda function as a complex to promote tumorigenesis. Molecularly, Par3/aPKClambda cooperate to promote Akt, ERK and NF-kappaB signaling during tumor initiation to sustain growth, whereas aPKClambda dominates in promoting survival. In the inflammatory tumorigenesis phase Par3/aPKClambda cooperate to drive Stat3 activation and hyperproliferation. Unexpectedly, the reduced inflammatory signaling did not alter carcinogen-induced immune cell numbers but reduced IL-4 Receptor-positive stromal macrophage numbers in all mutant mice, suggesting that epidermal aPKClambda and Par3 promote a tumor-permissive environment. Importantly, aPKClambda also serves a distinct, carcinogen-independent role in controlling skin immune cell homeostasis. Collectively, our data demonstrates that Par3 and aPKClambda cooperate to promote skin tumor initiation and progression, likely through sustaining growth, survival, and inflammatory signaling. PMID- 29789716 TI - xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression. AB - Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC. PMID- 29789717 TI - Multicellular detachment generates metastatic spheroids during intra-abdominal dissemination in epithelial ovarian cancer. AB - Ovarian cancer is the most lethal gynecological cancer, where survival rates have had modest improvement over the last 30 years. Metastasis of cancer cells is a major clinical problem, and patient mortality occurs when ovarian cancer cells spread beyond the confinement of ovaries. Disseminated ovarian cancer cells typically spread within the abdomen, where ascites accumulation aids in their transit. Metastatic ascites contain multicellular spheroids, which promote chemo resistance and recurrence. However, little is known about the origin and mechanisms through which spheroids arise. Using live-imaging of 3D culture models and animal models, we report that epithelial ovarian cancer (EOC) cells, the most common type of ovarian cancer, can spontaneously detach as either single cells or clusters. We report that clusters are more resistant to anoikis and have a potent survival advantage over single cells. Using in vivo lineage tracing, we found that multicellular spheroids arise preferentially from collective detachment, rather than aggregation in the abdomen. Finally, we report that multicellular spheroids from collective detachment are capable of seeding intra-abdominal metastases that retain intra-tumoral heterogeneity from the primary tumor. PMID- 29789719 TI - Selective vulnerability of the primitive meningeal layer to prenatal Smo activation for skull base meningothelial meningioma formation. AB - Somatic activating mutations of smoothened (SMO), a component of the embryonic sonic hedgehog (SHH) signaling pathway, are found in 3-5% of grade I meningiomas, most of them corresponding to meningothelial meningiomas located at the anterior skull base. By generating different developmental stage-specific conditional activations in mice, we define a restricted developmental window during which conditional activation of Smo in Prostaglandin D2-synthase-positive mesoderm derived meningeal layer of the skull base results in meningothelial meningioma formation. We show a selective vulnerability of the arachnoid from the skull base to Smo activation to initiate tumor development. This prenatal period and specific topography are correlated to the timing and location of SHH signaling involvement in the formation of craniofacial and meninges patterning, strongly corroborating the hypothesis of a developmental origin for Smo-activated meningiomas. Finally, we provide preclinical in vitro evidence of the efficacy of the SMO-inhibitor Sonidegib, supporting further preclinical and clinical evaluation of targeted treatment for refractory SMO-mutant meningiomas. PMID- 29789718 TI - PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy induced senescence. AB - CDK4/6 inhibitors are being used to treat a variety of human malignancies. In well-differentiated and dedifferentiated liposarcoma their clinical promise is associated with their ability to downregulate the MDM2 protein. The downregulation of MDM2 following treatment with CDK4/6 inhibitors also induces many cultured tumor cell lines derived from different types of malignancies to progress from quiescence into senescence. Here we used cultured human cell lines and defined a role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells. Materials from our previous phase II trials with palbociclib were then used to demonstrate that expression of CDH18 protein was associated with response, measured as both progression-free survival and overall survival. This supports the hypothesis that the biologic transition from quiescence to senescence has clinical relevance for this class of drugs. PMID- 29789720 TI - Change in weight status from childhood to early adulthood and late adulthood risk of colon cancer in men: a population-based cohort study. AB - BACKGROUND: Although weight gain in mid- to late adult life is associated with an increased risk of colon cancer, it is unclear if increases or losses in weight from childhood to early adulthood are differentially associated with risks of adult colon cancer. METHODS: Weight and height were measured at 7 or 13 years and in early adulthood (17-26 years) in 64,675 boys in the Copenhagen School Health Records Register and the Danish Conscription Database. Cases of colon cancer (n = 751) were identified in the Danish Cancer Registry. Boys and young men were categorized as normal weight or overweight. Associations between changes in weight and colon cancer were examined using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with men with a normal weight at 7 years and in early adulthood, men with overweight at both ages had an increased risk of adult colon cancer (HR: 2.73, 95% CI 1.80-4.15). In contrast, men with overweight at 7 years, but not in early adulthood did not have an increased risk of colon cancer (HR: 0.73, 95% CI 0.35-1.54), nor did men with a normal weight at 7 years and overweight in early adulthood (HR: 1.28, 95% CI 0.96-1.70). Similar results were observed for weight status at age 13 years combined with early adulthood. CONCLUSIONS: Childhood overweight that persists into early adulthood is associated with an increased risk of colon cancer, whereas overweight that disappears before early adulthood or developed after childhood is not. PMID- 29789721 TI - Is leptin resistance the cause or the consequence of diet-induced obesity? AB - BACKGROUND/OBJECTIVES: Obesity is strongly associated with leptin resistance. It is unclear whether leptin resistance results from the (over)consumption of energy dense diets or if reduced leptin sensitivity is also a pre-existing factor in rodent models of diet-induced obesity (DIO). We here tested whether leptin sensitivity on a chow diet predicts subsequent weight gain and leptin sensitivity on a free choice high-fat high-sucrose (fcHFHS) diet. METHODS: Based upon individual leptin sensitivity on chow diet, rats were grouped in leptin sensitive (LS, n = 22) and leptin resistant (LR, n = 19) rats (P = 0.000), and the development of DIO on a fcHFHS diet was compared. The time-course of leptin sensitivity was measured over weeks in individual rats. RESULTS: Both on a chow and a fcHFHS diet, high variability in leptin sensitivity was observed between rats, but not over time per individual rat. Exposure to the fcHFHS diet revealed that LR rats were more prone to develop DIO (P = 0.013), which was independent of caloric intake (p >= 0.320) and the development of diet-induced leptin resistance (P = 0.769). Reduced leptin sensitivity in LR compared with LS rats before fcHFHS diet exposure, was associated with reduced leptin-induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3) levels in the dorsomedial and ventromedial hypothalamus (P <= 0.049), but not the arcuate nucleus (P = 0.558). CONCLUSIONS: A pre-existing reduction in leptin sensitivity determines the susceptibility to develop excessive DIO after fcHFHS diet exposure. Rats with a pre-existing reduction in leptin sensitivity develop excessive DIO without eating more calories or altering their leptin sensitivity. PMID- 29789722 TI - How to tell how much wasp stings will hurt. PMID- 29789723 TI - A potential cure for the common cold. PMID- 29789724 TI - A geyser spurts from one of Jupiter's icy moons. PMID- 29789725 TI - Stink bugs leave DNA footprints on produce. PMID- 29789726 TI - Worm-eating mountain mice showcase evolution in action. PMID- 29789727 TI - Soaring overdose death rate fuels rise in organ transplantation. PMID- 29789728 TI - Why dinosaurs arranged their eggs in a doughnut shape. PMID- 29789730 TI - A double-pronged attack on colon tumours succeeds where one doesn't. PMID- 29789729 TI - Europe's open-access drive escalates as university stand-offs spread. PMID- 29789731 TI - Hawaii volcano eruption holds clues to predicting similar events elsewhere. PMID- 29789733 TI - Why your feet slip and slide on ice. PMID- 29789734 TI - Customers put off electric cars ... by electric-car sales staff. PMID- 29789732 TI - Experimental drugs poised for use in Ebola outbreak. PMID- 29789736 TI - Recruit young scientists and local talent to safeguard coral reefs. PMID- 29789737 TI - Chilean Atacama site imperilled by lithium mining. PMID- 29789738 TI - Risks from technology-critical metals after extraction. PMID- 29789739 TI - Publish translations of the best Chinese papers. PMID- 29789741 TI - Pulsars seen through a new lens. PMID- 29789742 TI - Plasmon propagation pushed to the limit. PMID- 29789743 TI - Sizing up human brain evolution PMID- 29789744 TI - How to fit in when you join a lab abroad. PMID- 29789745 TI - The cost of a warming climate. PMID- 29789746 TI - Chinese satellite launch kicks off ambitious mission to Moon's far side. PMID- 29789747 TI - An ultralight way to manipulate brain signals. PMID- 29789748 TI - S ingle-cell approaches to immune profiling. PMID- 29789749 TI - The global south is rich in sustainability lessons that students deserve to hear. PMID- 29789750 TI - Indonesian plan to clamp down on foreign scientists draws protest. PMID- 29789751 TI - Beware: transparency rule is a Trojan Horse. PMID- 29789752 TI - Science needs clarity on Europe's data-protection law. PMID- 29789754 TI - AHR ensures cells rest in peace. PMID- 29789755 TI - Regulatory mechanisms in T cell receptor signalling. AB - The remarkable T cell receptor (TCR) performs essential functions in the initiation of intracellular signals required for T cell development, repertoire selection and effector responses to foreign antigens. How TCR signals elicit such diverse cellular responses and outcomes remains a major question for investigation. Recent years have witnessed important advances in our understanding of the regulatory processes that control and modulate the TCR signalling response. Here, we review newly identified mechanisms for the regulation of TCR signalling and then discuss how the TCR signalling response is regulated to control two critical cellular processes - namely, positive selection and T cell homeostasis. PMID- 29789756 TI - IRF8: identity-keeper for suppressive Th1-like Treg cells. PMID- 29789753 TI - Hydrogen protects lung from hypoxia/re-oxygenation injury by reducing hydroxyl radical production and inhibiting inflammatory responses. AB - Here we investigated whether hydrogen can protect the lung from chronic injury induced by hypoxia/re-oxygenation (H/R). We developed a mouse model in which H/R exposure triggered clinically typical lung injury, involving increased alveolar wall thickening, infiltration by neutrophils, consolidation, alveolar hemorrhage, increased levels of inflammatory factors and recruitment of M1 macrophages. All these processes were attenuated in the presence of H2. We found that H/R-induced injury in our mouse model was associated with production of hydroxyl radicals as well as increased levels of colony-stimulating factors and circulating leukocytes. H2 attenuated H/R-induced production of hydroxyl radicals, up regulation of colony-stimulating factors, and recruitment of neutrophils and M1 macrophages to lung tissues. However, H2 did not substantially affect the H/R induced increase in erythropoietin or pulmonary artery remodeling. Our results suggest that H2 ameliorates H/R-induced lung injury by inhibiting hydroxyl radical production and inflammation in lungs. It may also prevent colony stimulating factors from mobilizing progenitors in response to H/R-induced injury. PMID- 29789757 TI - Locally produced lactic acid bacteria for pathogen inactivation and odor control in fecal sludge. AB - Providing safe fecal sludge (FS) sanitation has remained an important goal of global communities because of the high risks imposed on human health of the exposure to un-sanitized FS. This study used lactic acid fermentation as a pre treatment technology to evaluate the sanitization effect of lactic acid bacteria (LAB) on FS. A combination of fermented rice flour and brown sugar was used as the medium to prepare LAB, and fecal coliforms were used as the indicator organisms. The addition of a LAB suspension grown in fermented rice flour and brown sugar to FS was studied to evaluate the survival of fecal coliforms. The pH decreased during ongoing lactic acid fermentation after the addition of the LAB suspension. The results revealed that fecal coliforms in reactors containing 1:1 and 2:1 w/w of FS and LAB suspension decreased to half of the initial concentration within seven days of the treatment process in comparison with that of the control reactor. Viable plate counts of 0.6 * 108, 0.9 * 108, and 2.4 * 108 CFU/100 mL were recorded from reactors 1:1, 2:1, and the control, respectively. The total elimination of the fecal coliforms below the detection limit (<3 log 10 CFU/100 mL) was observed in both reactors after 15-17 days, whereas the number of fecal coliforms remained at 2.3 * 108 CFU/100 mL in the control reactor. The fecal coliforms were eliminated because of the acidification caused by the LAB during the incubation time. The final pH in the treatment reactors 1:1 and 2:1 was 3.7 and 3.9. While the final pH in the control reactor was 7.91. The results revealed that the bacterial pathogens in FS can be completely eliminated through a low-cost technique and a simple lactic acid fermentation process. PMID- 29789758 TI - Advantages of intraoperative implant for interstitial brachytherapy for accelerated partial breast irradiation either frail patients with early-stage disease or in locally recurrent breast cancer. AB - Purpose: To describe the intraoperative multicatheter implantation technique for accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy (HDR-BT). Secondarily, to evaluate outcomes and toxicity in a series of 83 patients treated with this technique at our institution. Material and methods: Retrospective analysis of a series of patients treated with HDR-BT APBI after intraoperative multicatheter interstitial implant between November 2006 and June 2017 at our institution. We assessed cosmesis, toxicity, overall survival (OS), and disease-free survival (DFS). Results: Eighty-three patients were included: 59 patients (71.1%) with primary early-stage breast cancer and 24 (28.9%) with locally recurrent breast cancer. Tumorectomy was performed in all cases, with intraoperative tumor margin assessment and sentinel node biopsy. Median age was 82 years (range, 44-92). The total prescribed dose was 32 Gy (8 treatment fractions) in 60 patients (72.3%), and 34 Gy (10 fractions) in 23 patients (27.7%). Median follow-up was 40 months (range, 1-136 months). Three year OS and DFS in the recurrent and primary cancer groups were 87% vs. 89%, and 96 % vs. 97.8%, respectively. Five patients died from non-cancer related causes. No local relapses were observed. Rates of acute and late toxicity were low in both groups. The cosmesis was good or excellent in most of patients treated for primary disease; in patients who underwent salvage brachytherapy for local recurrence, cosmesis was good in 49 patients and fair in 6. Conclusions: This technique, although time-consuming, achieves good local disease control with a satisfactory toxicity profile in both early-stage and local recurrent breast cancer patients. It may be especially suitable for frail patients. PMID- 29789759 TI - Combined external beam radiotherapy and vaginal brachytherapy versus vaginal brachytherapy in stage I, intermediate- and high-risk cases of endometrium carcinoma. AB - Purpose: Randomized trials on the effect of external beam radiotherapy (EBRT) with or without vaginal brachytherapy (VBT) for endometrial carcinoma are very few. In view of this, the current study was conducted with the hypothesizes: whether the escalated dose of 26 Gy (VBT alone) in comparison with various major international trials (PORTEC-2) has any difference in rates of disease-free and overall survival with fewer adverse effects in low resource setting like India. Material and methods: An open-labeled, non-inferiority, randomized control trial was undertaken at a regional cancer center among patients with stage IA or IB high-intermediate risk endometrial carcinoma. A total of 50 patients were divided equally among two arms of combined EBRT with VBT (arm I) and VBT alone (arm II). A dose of 50-50.4 Gy in 25-28 fractions of EBRT with 2 fractions of VBT 6.5 Gy each were delivered to patients in arm I and 4 fractions of VBT 6.5 Gy each to patients in arm II, and were followed up for 60 months. Results: During the median follow-up of 36.5 months, two patients developed loco-regional recurrence in arm II, three (arm II), and one (arm I) developed distant metastasis. The 5 year survival rates for arms I and II were 96.0% vs. 92.0% overall, and 88.0% vs. 84.0% disease-free, respectively, and were not found to be statistically significantly different. Dermatological, gastro-intestinal toxicities, and cystitis were lower in the VBT group compared to combined group. Conclusions: VBT alone is as effective as EBRT+VBT in ensuring loco-regional control and achieving comparable survival rates, with fewer toxic effects for patients with stage I intermediate- and high-risk endometrial carcinoma. The dose escalation did not make a difference in the survival rates and was like in the other major trials (PORTEC-2). PMID- 29789760 TI - High-dose-rate brachytherapy in treatment of non-melanoma skin cancer of head and neck region: preliminary results of a prospective single institution study. AB - Purpose: Skin cancers are the most common human malignancy with increasing incidence. Currently, surgery is standard of care treatment for non-melanoma skin cancers. However, brachytherapy is a growing modality in the management of skin cancers. Therefore, we aimed to assess the outcome of patients with non-melanoma skin cancers treated by high-dose-rate (HDR) brachytherapy with surface mold technique. Material and methods: In this prospective study, we recruited patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin who were candidates for definitive or adjuvant brachytherapy during 2013-2014. Alginate was used for making the individualized surface molds for each patient. Patients were treated with afterloading radionuclide HDR brachytherapy machine, with a total dose of 30-52 Gy in 10-13 fractions. Participants were followed for 2 years for radiation toxicity, cosmetic results, and local failures. Results: A total of 60 patients (66.7% male; median age, 71 years) were included, of which 42 (70.0%) underwent definitive radiotherapy. Seventy-five percent of lesions were BCC. The mean total dose was 39.6 +/- 5.4 Gy. Of patients in definitive group, 40/42 (95.2%) experienced complete clinical response after 3 months. The recurrence rate was 2/18 (11.11%) and 1/42 (2.38%) in adjuvant and definitive groups, respectively. The percentage of grade 3-4 acute (3-month post-treatment) and late toxicities (2 years post-treatment) was 6.7% and 0%, respectively. The cosmetic results were good/excellent in 96.2% of patients after 2 years of follow up. Conclusions: With appropriate patient selection and choosing as lowest dose per fraction as possible, HDR brachytherapy with customized surface molds yields good oncological and cosmetic results for the treatment of localized skin BCC and SCC. PMID- 29789761 TI - Visual outcome after posterior uveal melanoma episcleral brachytherapy including radiobiological doses. AB - Purpose: To assess the long-term influence of radiobiological doses in the evolution of visual acuity (VA) in patients with uveal melanoma treated by episcleral brachytherapy. Material and methods: Visual acuity was evaluated prospectively from a case series of 243 patients in 2016 treated with 125I. Data analysis was applied to trend VA outcome and find the accurate best-fit line. Biologically effective dose (BED) was included in survival analysis with the use of Kaplan-Meier and Cox regressions. Hazard ratio (HR) and confidence interval at 95% (CI) were determined. Variables statistically significant were analyzed and compared by log-rank tests. Results: The median follow-up was 74.2 months (range, 3-223). Exponential regression shows a 25% reduction and 50% in visual acuity score (VAS) scale for 5 and 27.8 months, respectively. Cumulative probabilities of survival analysis were 57%, 42%, 27%, and 23% at 3, 5, 10, and 15 years, respectively. Multivariable analysis found tumor height (HR = 1.18, 95% CI: 1.07 1.29), applicator size (HR = 1.22, 95% CI: 1.08-1.36), juxtapapillary localization (HR = 1.70, 95% CI: 1.01-2.84), and dose to foveola (HR = 1.01, 95% CI: 1.00-1.01) significantly associated with VA loss. Log-rank tests were significant for all those variables. BED has a strong influence in univariate model, but not statistically significant in the multivariate one. Conclusions: Visual acuity changes can be modeled by an exponential function for the first 5 years after treatment. No relation between VA loss and BED has been found; nevertheless, apical height, plaque size, juxtapapillary localization, and dose to fovea were found as statistical significant variables. PMID- 29789762 TI - Percutaneous computed tomography-guided permanent 125I implantation as therapy for pulmonary metastasis. AB - Purpose: To evaluate intermediate-term outcomes after computed tomography (CT) guided radioactive 125I seed implantation (CTRISI), and to determine prognostic variables associated with outcomes in patients with pulmonary metastases. Material and methods: Thoracic surgeons evaluated and performed implantation of 125I radioactive seeds under CT guidance or combined with surgical resection. Patients were monitored in the thoracic surgery clinic for recurrence and survival. Results: Fifty patients (31 men, 19 women; median age, 59 years; range, 16-85) underwent CTRISI. The primary cancer was colorectal in 10 (20%), malignant fibrous histiocytoma in 8 (16%), sarcoma in 5 (10%), renal in 4 (8%), and other in 22 (44%) patients. CTRISI was the sole treatment in 45 patients (90%) and was combined with surgical resection in 5 patients (10%). The actuarial D90 of implanted 125I seeds ranged from 90 to 160 Gy (median, 120 Gy). No procedurally related deaths occurred. At a median follow-up of 41.5 months (range, 7-74 months), 6 patients were alive. The median survival time was 42.1 months (95% confidence interval: 26.5-53.4), and the estimated 1-, 3-, and 5-year overall survival rates were 88.0%, 58.0%, and 26.7%, respectively. Lesion size was an important prognostic variable associated with overall and progression-free survival (p < 0.05). Conclusions: CTRISI is safe in this group of patients with pulmonary metastases and provides reasonable results. Surgical resection remains the standard for resectable cases, but CTRISI offers an alternative for selected patients or may be used as a feasible approach in combination with surgical resection for selected patients. PMID- 29789763 TI - Verification of high-dose-rate brachytherapy treatment planning dose distribution using liquid-filled ionization chamber array. AB - Purpose: This study aims to investigate the dosimetric performance of a liquid filled ionization chamber array in high-dose-rate (HDR) brachytherapy dosimetry. A comparative study was carried out with air-filled ionization chamber array and EBT3 Gafchromic films to demonstrate its suitability in brachytherapy. Material and methods: The PTW OCTAVIUS detector 1000 SRS (IA 2.5-5 mm) is a liquid-filled ionization chamber array of area 11 x 11 cm2 and chamber spacing of 2.5-5 mm, whereas the PTW OCTAVIUS detector 729 (IA 10 mm) is an air vented ionization chamber array of area 27 x 27 cm2 and chamber spacing of 10 mm. EBT3 films were exposed to doses up to a maximum of 6 Gy and evaluated using multi-channel analysis. The detectors were evaluated using test plans to mimic a HDR intracavitary gynecological treatment. The plan was calculated and delivered with the applicator plane placed 20 mm from the detector plane. The acquired measurements were compared to the treatment plan. In addition to point dose measurement, profile/isodose, gamma analysis, and uncertainty analysis were performed. Detector sensitivity was evaluated by introducing simulated errors to the test plans. Results: The mean point dose differences between measured and calculated plans were 0.2% +/- 1.6%, 1.8% +/- 1.0%, and 1.5% +/- 0.81% for film, IA 10 mm, and IA 2.5-5 mm, respectively. The average percentage of passed gamma (global/local) values using 3%/3 mm criteria was above 99.8% for all three detectors on the original plan. For IA 2.5-5 mm, local gamma criteria of 2%/1 mm with a passing rate of at least 95% was found to be sensitive when simulated positional errors of 1 mm was introduced. Conclusion: The dosimetric properties of IA 2.5-5 mm showed the applicability of liquid-filled ionization chamber array as a potential QA device for HDR brachytherapy treatment planning systems. PMID- 29789764 TI - A single institution analysis of low-dose-rate brachytherapy: 5-year reported survival and late toxicity outcomes. AB - Purpose: To report the 5-year biochemical relapse-free survival (BRFS), overall survival (OS), and long-term toxicity outcomes of patients treated with low-dose rate (LDR) brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Material and methods: Between 2004 and 2011, 371 patients were treated with LDR brachytherapy as monotherapy. Of these, 102 patients (27%) underwent transurethral resection of the prostate (TURP) prior to implantation. Follow-up was performed every 3 months for 12 months, then every 6 months over 4 years and included prostate specific antigen evaluation. The biochemical relapse-free survival (BRFS) was defined according to the Phoenix criteria. Acute and late toxicities were documented using the Common Terminology Criteria for Adverse Events version 4.0. The BRFS and OS estimates were calculated using Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. Results: The median follow-up of all patients was 5.45 years. The 5-year BRFS and OS rates were 95% and 96%, respectively. The BRFS rates for patients with Gleason score (GS) > 7 and GS <= 6 were 96% and 91% respectively (p = 0.06). On univariate analysis, T1 and T2 staging, risk-group classification, and prostate volumes had no impact on survival at 5 years (p > 0.1). Late grade 2 and 3 genitourinary (GU) toxicities were observed in 10% and 5% of patients respectively. Additionally, patients with prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p = 0.001). There were 14 deaths in total; however, none were attributed to prostate cancer. Conclusions: LDR brachytherapy is an effective treatment option in low- to intermediate-risk prostate cancer patients. We observed low biochemical relapse rates and minimal GU toxicities several years after treatment in patients with or without TURP. However, a small risk of urinary retention was observed in some patients. PMID- 29789765 TI - Successful salvage treatment of refractory recurrence of maxillary sinus carcinoma using image-guided high-dose-rate interstitial brachytherapy. AB - This case report illustrates a treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of maxillary sinus carcinoma. A 61-year-old male was previously admitted to another hospital and received surgery because of left maxillary sinus squamous cell carcinoma (SCC) 6 years ago. Tumor regrowth was noted 2 years after the initial radical surgery. The patient accepted local excision again for the recurrence, followed by external beam radiotherapy. Despite salvage treatment with surgery and external irradiation, the lesion expanded as 4.8 * 4.4 * 4.0 cm3. Because the patient refused palliative resection, we recommended technique of image-guided HDR interstitial brachytherapy. The total doses of 42 Gy in 12 fractions were delivered to the whole recurrent tumor. Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy, guided with ultrasound. The refractory tumor in the patient healed uneventfully after HDR interstitial brachytherapy without recurrence during 8 months of follow-up. This case is remarkable because the patient experienced complete remission by a safe and practicable method with image-guided HDR interstitial brachytherapy. PMID- 29789767 TI - Don't forget the bladder! PMID- 29789766 TI - Salvage high-dose-rate brachytherapy for prostate cancer persistence after brachytherapy: repeated use of a polyethylene glycol hydrogel spacer. AB - Purpose: The aim of this study is to determine if a repeated hydrogel injection in a previously irradiated patient prior to salvage high-dose-rate brachytherapy (HDR-BT) is feasible. Material and methods: A 61-year-old man with an organ confined (cT1c cN0 cM0, Gleason score 3 + 3 = 6, initial prostate-specific antigen [PSA] 7.9 ng/ml) prostate cancer was previously treated with HDR-BT (3 fractions of 11.5 Gy every 2nd week) after hydrogel injection to reduce the rectal dose. Ten months after, an isolated local persistence was seen on a PSMA PET-CT. Nadir PSA was 2.0 ng/ml, 3 months after treatment and was 3.95 ng/ml by the re-treatment. Salvage therapy consisted of HDR-BT (3 fractions of 9 Gy every 2nd week) with a simultaneous integrated boost to the residual region. Again, a hydrogel injection (10 ml) was applied to reduce the rectal dose prior to the treatment. Results: Both hydrogel injection and salvage HDR-BT could be applied without any significant complications or toxicity. A good PSA response was observed with a nadir of 0.42 ng/ml, twelve months after salvage therapy. Acute toxicity (max grade II) resolved within 2 days after treatment. Conclusions: The use of a hydrogel prior to salvage HDR-BT in a patient previously treated with HDR-BT is feasible and could help reduce the rectal exposure in the salvage setting. PMID- 29789768 TI - Radiological and clinical findings following rectal contact X-ray brachytherapy (Papillon technique) - how to assess response. AB - Purpose: Rectal contact X-ray brachytherapy (Papillon radiotherapy) has recently received approval from the National Institute for Health and Care Excellence. In particular, it is suitable for elderly patients who are high-risk for a major operation, but it may also be undertaken for patients who wish to avoid a stoma. It is imperative to be able to identify clinical response or tumor regrowth on surveillance magnetic resonance imaging (MRI) and sigmoidoscopy. This article aims to help clinicians to interpret MRIs and endoscopic appearances following Papillon radiotherapy. Material and methods: MRI and sigmoidoscopy images are presented from a case series of seven non-consecutive, heterogeneously treated patients with T2 to 3C N0 rectal adenocarcinoma. Treatments included transanal excision, adjuvant or neoadjuvant chemo/radiotherapy, and Papillon radiotherapy. These patients wished to avoid a stoma or were high-risk for a major operation. These cases have been chosen to demonstrate response assessment alone. Results: The "black spider" sign of maturing, low signal fibrosis on MRI was found to be reassuring, as was the presence of a flat scar on endoscopy. Residual tumor mass or intermediate signal suggest equivocal response, which may necessitate transanal excision. Loss of low signal fibrosis, or the development of soft tissue nodularity or mass should prompt biopsy. Conclusions: MR scans should be used in combination with endoluminal mucosal assessment (and digital rectal examination) to determine response following Papillon radiotherapy. This is the first paper to describe both the endoscopic and imaging findings following Papillon radiotherapy. PMID- 29789771 TI - Clinical study to monitor dentinal hypersensitivity with episodic use of a desensitising dentifrice. AB - Objectives/Aims: To evaluate continuous and episodic twice-daily usage regimens of a desensitising dentifrice containing 5% calcium sodium phosphosilicate (CSPS). Materials and Methods: In this exploratory, single-centre, randomised, examiner-blind study, subjects with dentinal hypersensitivity were randomised to continuous (24 weeks) use of a 5% CSPS-containing dentifrice or episodic use of the dentifrice comprising two 8-week treatment periods separated by 8 weeks' use of a standard fluoride dentifrice. Sensitivity was assessed by tactile threshold (Yeaple probe) and evaporative (air) sensitivity (Schiff sensitivity score). Other measures included labelled magnitude scales to assess subjects' responses to the evaporative stimulus, the Dentine Hypersensitivity Experience Questionnaire and a tooth sensitivity question. Results: Seventy-six subjects were randomised to continuous (n=38) or episodic (n=38) use. Small but statistically significant improvements from baseline in Schiff sensitivity scores were observed at weeks 8, 16 and 24 with both regimens (all P<0.05). Increases from baseline in tactile threshold were not statistically significant. No significant between-regimen difference was observed for any endpoint. No treatment-related adverse events were reported. Discussion: Dentifrice containing 5% CSPS improved dentinal hypersensitivity with both episodic and continuous twice-daily usage regimens over 24 weeks and was well tolerated. Conclusion: No performance differences were observed between the two usage regimens. PMID- 29789772 TI - Relevance of investigating light transmittance through red protective shields in dentistry. PMID- 29789773 TI - Reply to: Relevance of investigating light transmittance through red protective shields in dentistry. PMID- 29789770 TI - What do expectant mothers need to know about oral health? A cohort study from a London maternity unit. AB - Objective: To determine the oral health knowledge of pregnant women and to report their future plans to provide dental care for their expected child. Design and setting: Prospective cohort study; Ultrasound maternity services at St Thomas' Hospital, London, 2014. Pregnant women attending for a routine ultrasound scan completed a questionnaire. Results: Women did not know that milk, dried fruit or fruit juices can cause caries. Most women knew about the benefit of fluoridated toothpaste, dental floss and sugar-free chewing gum, but only a minority knew about fluoride varnish. Most pregnant women planned to read or seek advice before purchasing their child's first toothpaste. There was no difference regarding knowledge of prevention tools (diet and fluoride supplements) for dental caries (P>0.05) between first-time mothers and those who had children already. Though the latter knew more about toothpaste dose and timing of starting toothbrushing (P<0.05). Discussion: Oral health knowledge among pregnant women was deficient with respect to the cariogenicity of prolonged night-time milk feeding, dried fruits and fruit juice consumption. There was also limited knowledge of the benefit of fluoride varnish and timing of starting toothbrushing. Conclusions: Oral health knowledge amongst pregnant women is still deficient in many aspects. In this study population the need to improve maternal knowledge was shown. PMID- 29780582 TI - The convergent epidemiology of tuberculosis and human cytomegalovirus infection. AB - Although several factors are known to increase the risk of tuberculosis, the occurrence of tuberculosis disease in an infected individual is difficult to predict. We hypothesize that active human cytomegalovirus infection due to recent infection, reinfection or reactivation plays an epidemiologically relevant role in the aetiology of tuberculosis by precipitating the progression from latent tuberculosis infection to disease. The most compelling support for this hypothesis comes from the striking similarity in age-sex distribution between the two infections, important because the age-sex pattern of tuberculosis disease progression has not been convincingly explained. Cytomegalovirus infection and tuberculosis have other overlapping risk factors, including poor socio-economic status, solid organ transplantation and, possibly, sexual contact and whole blood transfusion. Although each of these overlaps could be explained by shared underlying risk factors, none of the epidemiological observations refute the hypothesis. If this interaction would play an epidemiologically important role, important opportunities would arise for novel approaches to controlling tuberculosis. PMID- 29789774 TI - Pilot Study of Dose-Response Effects of Exercise on Change in C-Reactive Protein, Cortisol, and Health-Related Quality of Life Among Cancer Survivors. AB - Fatigue, stress, and depression contribute to poor health-related quality of life (HRQoL) among cancer survivors. This study examined the effects of combined aerobic and resistance training (CART) on HRQoL and biomarkers of stress. Cancer survivors (n = 76, 91% female, 39% breast cancer, 32% gynecologic cancer) were enrolled in CART for three 60-min sessions, weekly, for 26 weeks. Participants completed the National Institutes of Health's Patient Reported Outcomes Measurement Information System (NIH PROMIS) fatigue assessment and the SF-36. Cortisol and c-reactive protein (CRP) were assessed using volunteered blood specimens. Baseline fatigue scores were worse for participants completing treatment within the last year, compared to long-term survivors [F = (2, 59) = 3.470, p = 0.038]. After 26 weeks, fatigue scores improved by a noteworthy two points [M = 52.72, standard deviation, SD = 10.10 vs. M = 50.67, SD = 10.14; t(48) = 1.7145, p = 0.092]. Pre- to postintervention improvements in bodily pain [M = 50.54, SD = 9.51 vs. M = 48.20, SD = 10.07; t(33) = 2.913, p = 0.006] and limitations in social functioning [M = 50.60, SD = 9.17 vs. M = 47.75, SD = 11.66; t(33) = 2.206, p = 0.034], as well as a mean decrease of 1.64 +/- 10.11 mg/L in CRP levels [t(107) = 1.261, p = 5.965], were observed. Participants within 1 year of treatment completion experienced greater improvements in post CRP levels compared to those who had treatment 1-4 years (p = 0.030) and 5 or more years ago (p = 0.023). Physical functioning, fatigue, fear/anxiety, social role satisfaction, and CRP levels improved following participation in this exercise intervention. Oncologists should consider recommending CART as soon as medically feasible following the cessation of cancer treatment. PMID- 29789775 TI - Pathological Internet Use-An Important Comorbidity in Child and Adolescent Psychiatry: Prevalence and Correlation Patterns in a Naturalistic Sample of Adolescent Inpatients. AB - Background: Few studies have examined the prevalence of problematic internet use (PIU) in young people undergoing inpatient treatment in child and adolescent psychiatry centers. The aims of our study were thus (a) to assess the frequency of comorbid PIU in a sample of adolescent psychiatric inpatients and compare it with a control group of nonreferred adolescents and (b) to gain insights into correlations between PIU and psychiatric comorbidities. Methods: 111 child and adolescent psychiatry inpatients (CAP-IP, mean age 15.1 +/- 1.4 years; female : male 72.4% : 27.6%) undergoing routine psychodiagnostics were screened for the presence of PIU. The widely used Compulsive Internet Use Scale (CIUS) was chosen for this purpose. Prevalence rates of PIU were then compared to matched nonreferred control subjects from a school sample. Additionally, comorbidities of inpatients with PIU were compared to inpatients without PIU. Results: Our inpatient sample showed a much higher prevalence of PIU than that found in previous populational samples of young people. Compared with a matched school sample, addictive internet use was 7.8 times higher and problematic internet use 3.3 times higher among our adolescent sample. PIU was significantly associated with characteristic patterns of psychopathology, that is, suicidality, difficulties in establishing stable and consolidated identity, and peer victimization. Conclusion: PIU among adolescents undergoing inpatient psychiatric treatment is much more frequent than among their peers in the general population and is associated with specific patterns of psychopathology. PMID- 29789776 TI - Effect of Electromagnetic Waves from Mobile Phones on Spermatogenesis in the Era of 4G-LTE. AB - Objective: To investigate the effect of long duration exposure to electromagnetic field from mobile phones on spermatogenesis in rats using 4G-LTE. Methods: Twenty Sprague-Dawley male rats were placed into 4 groups according to the intensity and exposure duration: Group 1 (sham procedure), Group 2 (3 cm distance + 6 h exposure daily), Group 3 (10 cm distance + 18 h exposure daily), and Group 4 (3 cm distance + 18 h exposure daily). After 1 month, we compared sperm parameters and histopathological findings of the testis. Results: The mean spermatid count (*106/ml) was 398.6 in Group 1, 365.40 in Group 2, 354.60 in Group 3, and 298.60 in Group 4 (p = 0.041). In the second review, the mean count of spermatogonia in Group 4 (43.00) was significantly lower than in Group 1 (57.00) and Group 2 (53.40) (p < 0.001 and p = 0.010, resp.). The sum of the germ cell counts was decreased in Group 4 compared to Groups 1, 2, and 3 (p = 0.032). The mean Leydig cell count was significantly decreased in Group 4 (p < 0.001). Conclusions: The longer exposure duration of electromagnetic field decreased the spermatogenesis. Our findings warrant further investigations on the potential effects of EMF from mobile phones on male fertility. PMID- 29789777 TI - A Normalized Shear Deformation Indicator for Ultrasound Strain Elastography in Breast Tissues: An In Vivo Feasibility Study. AB - The shear deformation under loads contains useful information for distinguishing benign breast lesions from malignant ones. In this study, we proposed a normalized shear deformation indicator (NSDI) that was derived from the concept of principal strains. Since the NSDI requires both high-quality axial and lateral (parallel and perpendicular to the beam, resp.) displacement estimates, a strategy combining high-quality speckle tracking with signal "denoising" was employed. Both techniques were previously published by our group. Finite element (FE) models were used to identify possible causes for elevated NSDI values in and around breast lesions, followed by an analysis of ultrasound data acquired from 26 biopsy-confirmed in vivo breast lesions. We found that, theoretically, the elevated NSDI values could be attributed to two factors: significantly hardened tissue stiffness and increasing heterogeneity. The analysis of in vivo data showed that the proposed NSDI values were higher (p < 0.05) among malignant cancers as compared to those measured from benign ones. In conclusion, our preliminary results demonstrated that the calculation of NSDI value is feasible and NSDI could add value to breast lesion differentiation with current clinical equipment as a postprocessing tool. PMID- 29789778 TI - Conscious Sedation versus General Anesthesia for Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-Analysis. AB - The aim of this study is to compare the effect of conscious sedation (CS) with general anesthesia (GA) on clinical outcomes in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT). MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017) were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ? 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ? 2 at hospital discharge and one or three months was increased. PMID- 29789780 TI - Quantitative Motion Analysis of Tai Chi Chuan: The Upper Extremity Movement. AB - The quantitative and reproducible analysis of the standard body movement in Tai Chi Chuan (TCC) was performed in this study. We aimed to provide a reference of the upper extremities for standardizing TCC practice. Microsoft Kinect was used to record the motion during the practice of TCC. The preparation form and eight essential forms of TCC performed by an instructor and 101 practitioners were analyzed in this study. The instructor completed an entire TCC practice cycle and performed the cycle 12 times. An entire cycle of TCC was performed by practitioners and images were recorded for statistics analysis. The performance of the instructor showed high similarity (Pearson correlation coefficient (r) = 0.71 ~ 0.84) to the first practice cycle. Among the 9 forms, lay form had the highest similarity (rmean = 0.90) and push form had the lowest similarity (rmean = 0.52). For the practitioners, ward off form (rmean = 0.51) and roll back form (rmean = 0.45) had the highest similarity with moderate correlation. We used Microsoft Kinect to record the spatial coordinates of the upper extremity joints during the practice of TCC and the data to perform quantitative and qualitative analysis of the joint positions and elbow joint angle. PMID- 29789779 TI - Outcomes in Cardiogenic Shock Patients with Extracorporeal Membrane Oxygenation Use: A Matched Cohort Study in Hospitals across the United States. AB - Background: ECMO is increasingly used for patients with critical illnesses. This study examines ECMO use in patients with cardiogenic shock in US hospitals and associated outcomes (mortality, hospital length of stay, and total hospital charges). Methods: A matched cohort retrospective study was conducted using the 2013 Nationwide Emergency Department Sample. Cardiogenic shock visits were matched (1 : 1) and compared based on ECMO use. Results: Patients with ECMO (N = 802) were compared to patients without ECMO (N = 805). Mortality was higher in the ECMO group (48.9% versus 4.0%, p < 0.001). Visits with ECMO use also had higher average hospital charges ($580,065.8 versus $156,436.5, p < 0.001) and average hospital LOS (21.3 versus 11.6 days, p < 0.001). After adjusting for confounders, mortality (OR = 8.52 (95% CI: 2.84-25.58)) and charges (OR = 1.03 (95% CI: 1.02-1.05)) remained higher in the ECMO group, while LOS was similar (OR = 1.01 (95% CI: 0.99-1.02)). Conclusions: Patients with cardiogenic shock who underwent ECMO had increased mortality and higher cost of care without significant increase in LOS when compared to patients with cardiogenic shock without ECMO use. Prospective evaluation of this observed association is needed to improve outcomes and resources' utilization further. PMID- 29789781 TI - Serum Cystatin C Level Is Not a Promising Biomarker for Predicting Clinicopathological Characteristics of Bladder Urothelial Tumors. AB - The role of cystatin C (Cys-C) in tumorigenesis and progression of bladder urothelial tumors (BUT) is still indefinite. We retrospectively collected the clinical information from the records of 425 BUT patients. Pretreatment serum Cys C levels were compared across the various groups. Then we subgroup the patients with GFR >= 90 mg/min/1.73 m2, to exclude the effects of lower renal function on cystatin C. No statistically significant differences in the levels of serum Cys-C were found among the tumor characteristics (all P > 0.05). In conclusion, circulating Cys-C was not a reliable predictor for clinicopathological characteristics of BUT patients. PMID- 29789782 TI - Natural History of Postoperative Adding-On in Adolescent Idiopathic Scoliosis: What Are the Risk Factors for Progressive Adding-On? AB - Purpose: To investigate the natural history of distal adding-on in adolescent idiopathic scoliosis (AIS) and to identify risk factors for its progression. Methods: Sixty-one AIS patients with distal adding-on occurrence were included. We further classify distal adding-on into progressive and nonprogressive group according to its natural evolution. The first radiograph indicating initiation of adding-on (primary adding-on) and the last follow-up radiograph were compared in terms of the deviation of the first vertebra below instrumentation from the CSVL and the angulation of the first disc below instrumentation. Compared to primary adding-on, progressive adding-on was defined as a further increase of deviation > 5 mm or a further increase of angulation > 5 degrees . Risk factors associated with the progression of adding-on were analyzed. Results: Among 61 patients diagnosed with distal adding-on, 24 (39.3%) were progressive and 37 (60.7%) were nonprogressive. Lower Risser grade, open triradiate cartilage, and lowest instrumented vertebra (LIV) proximal to Substantially Stable Vertebra (SSV) were found to be significantly associated with the progressive adding-on. Besides, the distal adding-on was more likely to progress for patients with higher left shoulders than right ones after surgery. Conclusions: The risk factors for the progression of adding-on included skeletal immaturity, LIV proximal to SSV, and higher left shoulders after surgery. PMID- 29789783 TI - miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration. AB - Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT PCR. Using a dual-luciferase reporter assay, we found that miR-142-5p can bind to and decrease expression of VCAM-1 mRNA. Such reduction was prohibited when the miR-142-5p binding site in VCAM-1 3'UTR was deleted, and Western blotting analyses validated the fact that miR-142-5p inhibited the expression of VCAM-1 protein. Bone marrow-derived mesenchymal stem cells (BMMSCs) transfected with miR 142-5p showed a significantly decreased migration ability in a Transwell migration assay. Collectively, these data indicated the important role of miR-142 5p in osteoporosis development involving targeting VCAM-1 and inhibiting BMMSC migration. PMID- 29789786 TI - Isolation and Characterization of Two New Antimicrobial Acids from Quercus incana (Bluejack Oak). AB - Two new compounds [1-2] were purified from ethyl acetate fraction of Quercus incana. The structure of these compounds is mainly established by using advanced spectroscopic technique such as UV, IR, one-dimensional (ID) and two-dimensional (2D) NMR techniques, and EI mass. The structural formula was deduced to be 4 hydroxydecanoic acid [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. Both isolated compounds were tested for their antimicrobial potential and showed promising antifungal activity against Aspergillus niger and Aspergillus flavus. PMID- 29789784 TI - Canine Leishmaniasis: An Overview of the Current Status and Strategies for Control. AB - Canine leishmaniasis (CanL) is a vector-borne disease caused by Leishmania infantum and is transmitted by female phlebotomine sand flies primarily between animals and secondarily to humans. The course of infection may be different from one individual dog to another, ranging from spontaneous cure to acute evolution that leads to death, if proper management and therapy are not adopted. A parasitological cure is rarely achieved and clinical recurrences in CanL are frequent. Vaccination associated with the use of topical insecticides is undoubtedly the most effective form of prevention and control of the disease. In order to integrate the most important scientific knowledge of the literature in one objective publication, this review proposes a short overview of the main points of CanL. PMID- 29789785 TI - Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice. AB - Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo, which may have relevant consequences for the nutritional state and long term health of the organism. PMID- 29789788 TI - Development of Two Analytical Methods Based on Reverse Phase Chromatographic and SDS-PAGE Gel for Assessment of Deglycosylation Yield in N-Glycan Mapping. AB - N-lined glycosylation is one of the critical quality attributes (CQA) for biotherapeutics impacting the safety and activity of drug product. Changes in pattern and level of glycosylation can significantly alter the intrinsic properties of the product and, therefore, have to be monitored throughout its lifecycle. Therefore fast, precise, and unbiased N-glycan mapping assay is desired. To ensure these qualities, using analytical methods that evaluate completeness of deglycosylation is necessary. For quantification of deglycosylation yield, methods such as reduced liquid chromatography-mass spectrometry (LC-MS) and reduced capillary gel electrophoresis (CGE) have been commonly used. Here we present development of two additional methods to evaluate deglycosylation yield: one based on LC using reverse phase (RP) column and one based on reduced sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE gel) with offline software (GelAnalyzer). With the advent of rapid deglycosylation workflows in the market for N-glycan profiling replacing overnight incubation, we have aimed to quantify the level of deglycosylation in a selected rapid deglycosylation workflow. Our results have shown well resolved peaks of glycosylated and deglycosylated protein species with RP-LC method allowing simple quantification of deglycosylation yield of protein with high confidence. Additionally a good correlation, >=0.94, was found between deglycosylation yields estimated by RP-LC method and that of reduced SDS-PAGE gel method with offline software. Evaluation of rapid deglycosylation protocol from GlycanAssureTM HyPerformance assay kit performed on fetuin and RNase B has shown complete deglycosylation within the recommended protocol time when evaluated with these techniques. Using this kit, N-glycans from NIST mAb were prepared in 1.4 hr and analyzed by hydrophilic interaction chromatography (HILIC) ultrahigh performance LC (UHPLC) equipped with a fluorescence detector (FLD). 37 peaks were resolved with good resolution. Excellent sample preparation repeatability was found with relative standard deviation (RSD) of <5% for peaks with >0.5% relative area. PMID- 29789789 TI - Incidental Thoracic and Abdominal Findings in Diagnostic Imaging. PMID- 29789787 TI - Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases. AB - Serine/arginine-rich splicing factors (SRSFs) have one or two RNA recognition motifs in the N terminal and a serine/arginine-enriched domain in the C terminal. SRSFs are essential components of spliceosomes and are involved in alternative splicing, spliceosome assembly, mRNA export, and nonsense-mediated mRNA decay. The maintenance of cellular and tissue homeostasis relies on accurate alternative splicing, and various patterns of abnormal alternative splicing can cause different diseases. SRSF4 is associated with many physiological and pathological processes and has applications in the diagnosis and prognosis of specific diseases. In this review, we discuss knowledge of SRSF4 in physiological and pathological processes and highlight the applications of SRSF4 in the regulation of gene expression and associated diseases. PMID- 29789790 TI - Distinct Epitopes on CD13 Mediate Opposite Consequences for Cell Adhesion. AB - CD13 is a membrane glycoprotein with aminopeptidase activity, expressed on several cell types, including myeloid cells (dendritic cells, monocytes, macrophages, neutrophils, etc.). CD13 participates in several functions such as proteolytic regulation of bioactive peptides, viral receptor, angiogenesis, and tumor metastasis. CD13 has also been proposed to participate in cell adhesion, as crosslinking of CD13 by certain CD13-specific antibodies induces homotypic aggregation of monocytes and heterotypic adhesion of monocytes to endothelial cells. We generated two monoclonal antibodies (mAbs C and E) that block homotypic aggregation of U-937 monocytic cells induced by CD13-specific mAb 452. Moreover, the mAbs cause detachment of cells whose aggregation was induced by CD13 crosslinking. Both mAbs also inhibit heterotypic adhesion of U-937 monocytes to endothelial cells. mAbs C and E recognize membrane CD13 but bind to epitopes different from that recognized by mAb 452. Crosslinking of CD13 by mAb C or E is required to inhibit adhesion, as monovalent Fab fragments are not sufficient. Thus, C and E antibodies recognize a distinct epitope on CD13, and binding to this epitope interferes with both CD13-mediated cell adhesion and enzymatic activity. These antibodies may represent important tools to study cell-cell interactions mediated by CD13 in physiological and pathological conditions. PMID- 29789791 TI - Association between Insulin-Like Growth Factor-1 and Uric Acid in Chinese Children and Adolescents with Idiopathic Short Stature: A Cross-Sectional Study. AB - Objective: The aim of this study was to examine the relationship between insulin like growth factor-1 (IGF-1) and serum uric acid (UA) in Chinese children and adolescents with idiopathic short stature (ISS). Methods: A cross-sectional study of 91 Chinese children and adolescents with ISS was performed. Anthropometric measurements and biochemical parameters were tested. The standard deviation score of IGF-1 (IGF-1 SDS) was calculated. Results: A univariate analysis displayed a significant positive correlation between IGF-1 SDS and UA (P = 0.004). In multivariate piecewise linear regression, the levels of IGF-1 SDS increased with the elevation of UA when UA was between 168 MUmol/L and 301 MUmol/L (beta 0.010, 95% CI 0.004-0.017; P = 0.002). The levels of IGF-1 SDS decreased with the elevation of UA when UA was either less than 168 MUmol/L (beta -0.055, 95% CI 0.081--0.028; P < 0.001) or more than 301 MUmol/L (beta -0.005, 95% CI -0.013 0.002; P = 0.174). Conclusions: This study demonstrated a nonlinear relationship between IGF-1 and UA levels in Chinese children and adolescents with ISS. This finding suggests that either high or low levels of UA may have an adverse effect on IGF-1, whereas appropriate UA levels have a beneficial effect. PMID- 29789792 TI - Remote Ischemic Postconditioning Protects against Myocardial Ischemia-Reperfusion Injury by Inhibition of the RAGE-HMGB1 Pathway. AB - Background: The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods: Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement. The protein levels of RAGE, HMGB1, P-AKT, and ERK1/2 were detected by Western blot 120 min following reperfusion. Results: RIPostC could decrease the infarct size and increase LVEF and FS compared with I/R group. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. The level of p-AKT was significantly higher in the RIPostC group than in the I/R group. LY294002 significantly attenuated RIPostC-increased levels of Akt phosphorylation. Conclusion: RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness. PMID- 29789793 TI - Modern Myoma Treatment in the Last 20 Years: A Review of the Literature. AB - Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased "expulsive" forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time. PMID- 29789794 TI - Biodegradable Alginate-Chitosan Hollow Nanospheres for Codelivery of Doxorubicin and Paclitaxel for the Effect of Human Lung Cancer A549 Cells. AB - A biodegradable alginate coated chitosan hollow nanosphere (ACHN) was prepared by a hard template method and used for codelivery of doxorubicin (DOX) and paclitaxel (PTX) to investigate the effect on human lung cancer A549 cells. PTX was loaded into the nanometer hollow structure of ACHN through adsorption method. DOX was coated on surface of ACHN through electrostatic interaction. Drug release studies exhibited a sustained-release effect. According to X-ray diffraction patterns (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) analysis, DOX structure in the loading samples (DOX PTX-ACHN) was of amorphous state while PTX was microcrystalline. Cytotoxicity experiments showed ACHN was nontoxic as carrier material and the combination of DOX and PTX in DOX-PTX-ACHN exhibited a good inhibiting effect on cell proliferation. Cell uptake experiments demonstrated that DOX-PTX-ACHN accumulated in the cytoplasm. Degradation experiments illustrated that ACHN was a biodegradable material. In summary, these results clearly indicate that ACHN can be utilized as a potential biomaterial to transport multiple drugs to be used in combination therapy. PMID- 29789796 TI - Removal of Nitrate in Simulated Water at Low Temperature by a Novel Psychrotrophic and Aerobic Bacterium, Pseudomonas taiwanensis Strain J. AB - Low temperatures and high pH generally inhibit the biodenitrification. Thus, it is important to explore the psychrotrophic and alkali-resisting microorganism for degradation of nitrogen. This research was mainly focused on the identification of a psychrotrophic strain and preliminary explored its denitrification characteristics. The new strain J was isolated using the bromothymol blue solid medium and identified as Pseudomonas taiwanensis on the basis of morphology and phospholipid fatty acid as well as 16S rRNA gene sequence analyses, which is further testified to work efficiently for removing nitrate from wastewater at low temperature circumstances. This is the first report that Pseudomonas taiwanensis possessed excellent tolerance to low temperature, with 15 degrees C as its optimum and 5 degrees C as viable. The Pseudomonas taiwanensis showed unusual ability of aerobic denitrification with the nitrate removal efficiencies of 100% at 15 degrees C and 51.61% at 5 degrees C. Single factor experiments showed that the optimal conditions for denitrification were glucose as carbon source, 15 degrees C, shaking speed 150 r/min, C/N 15, pH >= 7, and incubation quantity 2.0 * 106 CFU/mL. The nitrate and total nitrogen removal efficiencies were up to 100% and 93.79% at 15 degrees C when glucose is served as carbon source. These results suggested that strain J had aerobic denitrification ability, as well as the notable ability to tolerate the low temperature and high pH. PMID- 29789795 TI - Clinical and Experimental Evidences of Hydrogen Sulfide Involvement in Lead Induced Hypertension. AB - Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (H2S) have been reported previously. However, no studies examined involvement of H2S in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished H2S plasmatic levels. In order to expand our findings, male Wistar rats were divided into four groups: Saline, Pb, NaHS, and Pb + NaHS. Pb-intoxicated animals received intraperitoneally (i.p.) 1st dose of 8 MUg/100 g of Pb acetate and subsequent doses of 0.1 MUg/100 g for seven days and sodium hydrosulfide- (NaHS-) treated animals received i.p. NaHS injections (50 MUmol/kg/twice daily) for seven days. NaHS treatment blunted increases in systolic blood pressure, increased H2S plasmatic levels, and diminished whole-blood lead levels. Treatment with NaHS in Pb-induced hypertension seems to induce a protective role in rat aorta which is dependent on endothelium and seems to promote non-NO-mediated relaxation. Pb intoxication increased oxidative stress in rats, while treatment with NaHS blunted increases in plasmatic MDA levels and increased antioxidant status of plasma. Therefore, H2S pathway may be involved in Pb-induced hypertension and treatment with NaHS exerts antihypertensive effect, promotes non-NO-mediated relaxation, and decreases oxidative stress in rats with Pb-induced hypertension. PMID- 29789797 TI - Impact of Static Magnetic Field on the Antioxidant Defence System of Mice Fibroblasts. AB - Results of research assessing the biological impact of static magnetic fields are controversial. So far, they have not provided a clear answer to their influence on cell functioning. Since the use of permanent magnets both in everyday life and in industry becomes more and more widespread, the investigations are continued in order to explain these controversies and to evaluate positive applications. The goal of current work was to assess the impact of static magnetic field of different intensities on redox homeostasis in cultures of fibroblasts. The use of permanent magnets allowed avoiding the thermal effects which are present in electromagnets. During the research we used 6 chambers, designed exclusively by us, with different values of field flux density (varying from 0.1 to 0.7 T). We have noted the decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The static magnetic fields did not modify the energy state of fibroblasts- adenosine triphosphate (ATP) concentration was stable, as well as the generation of malondialdehyde (MDA)-which is a marker of oxidative stress. Results of research suggest that static magnetic fields generated by permanent magnets do not cause oxidative stress in investigated fibroblasts and that they may show slight antioxidizing activity. PMID- 29789799 TI - The Impact of a Clinical Asthma Pathway on Resident Education. AB - Clinical pathways for asthma management decrease hospital cost and length of stay; however little is known about the educational impact of pathways on residents. Pediatric residents at a children's hospital (N = 114) were invited to complete a 22-item computerized, anonymous survey 6 months before and 6 months after asthma pathway implementation. The survey assessed pathway use and residents (1) pathway knowledge, (2) attitudes and experiences with managing asthma, and (3) perceived educational benefits. Mean pathway knowledge score increased from the case before to the case after implementation [1.5 +/- 1.0 versus 2.6 +/- 1.3, p < 0.001], as did high preparedness to manage asthma [61% versus 91%, p < 0.001] and electronic order set use [28% versus 80%, p < 0.001]. The top three educational benefits of the pathway endorsed by residents were application of evidence-based medicine (57%), ability to assess exacerbations (52%), and skill at communicating respiratory status (47%). After implementation, residents' knowledge and preparedness to manage asthma improved as well as many endorsed educational benefits. PMID- 29789798 TI - The Relation between Sarcopenia and Mortality in Patients at Intensive Care Unit. AB - Background and Aim: Psoas muscle area (PMA) can reflect the status of skeletal muscle in the whole body. It has been also reported that decreased PMA was associated with postoperative mortality or morbidity after several surgical procedures. In this study, we aimed to investigate the relation between PMA and mortality in all age groups in intensive care unit (UNIT). Materials and Method: The study consists of 362 consecutive patients. The demographic characteristics of patients, indications for ICU hospitalization, laboratory parameters, and clinical parameters consist of mortality and length of stay, and surgery history was obtained from intensive care archive records. Results: The mean age was 61.2 +/- 18.2 years, and the percentage of female was 33.3%. The mean duration of stay was 10.3 +/- 24.4 days. Exitus ratio, partial healing, and healing were 25%, 70%, and 5%, respectively. The mean right, left, and total PMA were 8.7 +/- 3.6, 8.9 +/- 3.4, and 17.6 +/- 6.9, respectively. The left and total PMA averages of the nonoperation patients were statistically significantly lower (p = 0.021 p = 0.043). The mean PMA between the ex and recovered patients were statistically significantly lower (p = 0.001, p = 0.001, p < 0.001). Dyspnoea, renal insufficiency, COPD, transfusion rate, operation rate, ventilator needy, and mean duration of hospitalization were statistically significant higher in patients with exitus. There is a significant difference in operation types, anesthesia type, and clinic rates. Conclusion: Our data suggest that sarcopenia can be used to risk stratification in ICU patients. Future studies may use this technique to individualize postoperative interventions that may reduce the risk for an adverse discharge disposition related to critical illness, such as early mobilization, optimized nutritional support, and reduction of sedation and opioid dose. PMID- 29789802 TI - Successful Formulation and Application of Plant Growth-Promoting Kosakonia radicincitans in Maize Cultivation. AB - The global market for biosupplements is expected to grow by 14 percent between 2014 and 2019 as a consequence of the proven benefits of biosupplements on crop yields, soil fertility, and fertilizer efficiency. One important segment of biosupplements is plant growth-promoting bacteria (PGPB). Although many potential PGPB have been discovered, suitable biotechnological processing and shelf-life stability of the bacteria are challenges to overcome for their successful use as biosupplements. Here, the plant growth-promoting Gram-negative strain Kosakonia radicincitans DSM 16656T (family Enterobacteriaceae) was biotechnologically processed and applied in the field. Solid or liquid formulations of K. radicincitans were diluted in water and sprayed on young maize plants (Zea mays L.). Shelf-life stability tests of formulated bacteria were performed under 4 degrees C and -20 degrees C storage conditions. In parallel, the bacterial formulations were tested at three different farm level field plots characterized by different soil properties. Maize yield was recorded at harvest time, and both formulations increased maize yields in silage as well as grain maize, underlining their positive impact on different agricultural systems. Our results demonstrate that bacteria of the family Enterobacteriaceae, although incapable of forming spores, can be processed to successful biosupplements. PMID- 29789800 TI - LraI from Lactococcus raffinolactis BGTRK10-1, an Isoschizomer of EcoRI, Exhibits Ion Concentration-Dependent Specific Star Activity. AB - Restriction enzymes are the main defence system against foreign DNA, in charge of preserving genome integrity. Lactococcus raffinolactis BGTRK10-1 expresses LraI Type II restriction-modification enzyme, whose activity is similar to that shown for EcoRI; LraI methyltransferase protects DNA from EcoRI cleavage. The gene encoding LraI endonuclease was cloned and overexpressed in E. coli. Purified enzyme showed the highest specific activity at lower temperatures (between 13 degrees C and 37 degrees C) and was stable after storage at -20 degrees C in 50% glycerol. The concentration of monovalent ions in the reaction buffer required for optimal activity of LraI restriction enzyme was 100 mM or higher. The recognition and cleavage sequence for LraI restriction enzyme was determined as 5'-G/AATTC-3', indicating that LraI restriction enzyme is an isoschizomer of EcoRI. In the reaction buffer with a lower salt concentration, LraI exhibits star activity and specifically recognizes and cuts another alternative sequence 5' A/AATTC-3', leaving the same sticky ends on fragments as EcoRI, which makes them clonable into a linearized vector. Phylogenetic analysis based on sequence alignment pointed out the common origin of LraI restriction-modification system with previously described EcoRI-like restriction-modification systems. PMID- 29789803 TI - The Productivity Dynamics of China's Environmentally Friendly Production Technologies in terms of Wastewater Treatment Techniques. AB - Low economic profit usually reduces the incentive of producers to operate their wastewater treatment technologies effectively. It is necessary to investigate the performance of environmentally friendly production technologies that reduce wastewater discharges and generate economic outputs simultaneously (EPTWs) in China over the past decade. In this paper, we apply the Malmquist-Luenberger productivity index widely used in the field of economics to evaluate the productivity change of EPTWs for 30 administrative provinces in China during 2003 2015. The pathways of the productivity change are further identified by decomposing the productivity index into two components: technological change and technical efficiency change. The results show that China's environmental productivity index associated with wastewater reduction had undergone a downward trend, and evident spatial disparities are observed among the 30 provincial regions. Moreover, the changes of China's environmental productivity over the whole studied period can mainly be attributed to technological progress, while the technical efficiency component has contributed little, although its annual contributing rate is in an increasing trend. PMID- 29789801 TI - Exercise Prevents Diaphragm Wasting Induced by Cigarette Smoke through Modulation of Antioxidant Genes and Metalloproteinases. AB - Background: The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). Methods: Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks. Gene expression of kelch-like ECH-associated protein 1; nuclear factor erythroid 2 like 2; and heme-oxygenase1 by polymerase chain reaction was performed. Metalloproteinases 2 and 9 activities were analyzed by zymography. Exercise capacity was evaluated by treadmill exercise test before and after the protocol. Results: Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure. This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training. The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group. Conclusions: Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases. PMID- 29789805 TI - In Silico Knockout Screening of Plasmodium falciparum Reactions and Prediction of Novel Essential Reactions by Analysing the Metabolic Network. AB - Malaria is an infectious disease that affects close to half a million individuals every year and Plasmodium falciparum is a major cause of malaria. The treatment of this disease could be done effectively if the essential enzymes of this parasite are specifically targeted. Nevertheless, the development of the parasite in resisting existing drugs now makes discovering new drugs a core responsibility. In this study, a novel computational model that makes the prediction of new and validated antimalarial drug target cheaper, easier, and faster has been developed. We have identified new essential reactions as potential targets for drugs in the metabolic network of the parasite. Among the top seven (7) predicted essential reactions, four (4) have been previously identified in earlier studies with biological evidence and one (1) has been with computational evidence. The results from our study were compared with an extensive list of seventy-seven (77) essential reactions with biological evidence from a previous study. We present a list of thirty-one (31) potential candidates for drug targets in Plasmodium falciparum which includes twenty-four (24) new potential candidates for drug targets. PMID- 29789806 TI - Different Membrane Pathways Mediate Ca2+ Influx in Adrenal Chromaffin Cells Exposed to 150-400 ns Electric Pulses. AB - Exposing adrenal chromaffin cells to 5 ns electric pulses (nsPEF) causes a rapid rise in intracellular Ca2+ ([Ca2+]i) that is solely the result of Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). This study explored the effect of longer duration nsPEF on [Ca2+]i. Single 150, 200, or 400 ns pulses at 3.1 kV/cm evoked rapid increases in [Ca2+]i, the magnitude of which increased linearly with pulse width and electric field amplitude. Recovery of [Ca2+]i to prestimulus levels was faster for 150 ns exposures. Regardless of pulse width, no rise in [Ca2+]i occurred in the absence of extracellular Ca2+, indicating that the source of Ca2+ was from outside the cell. Ca2+ responses evoked by a 150 ns pulse were inhibited to varying degrees by omega-agatoxin IVA, omega-conotoxin GVIA, nitrendipine or nimodipine, antagonists of P/Q-, N-, and L-type VGCCs, respectively, and by 67% when all four types of VGCCs were blocked simultaneously. The remaining Ca2+ influx insensitive to VGCC inhibitors was attributed to plasma membrane nanoporation, which comprised the E-field sensitive component of the response. Both pathways of Ca2+ entry were inhibited by 200 MUM Cd2+. These results demonstrate that, in excitable chromaffin cells, single 150 400 ns pulses increased the permeability of the plasma membrane to Ca2+ in addition to causing Ca2+ influx via VGCCs. PMID- 29789807 TI - Real-Time Measurement of Ocular Wavefront Aberrations in Symptomatic Subjects. AB - The purpose of this work was to study the real-time changes of the optical properties of the eye with accommodation in subjects with symptoms of accommodative disorders. From ocular aberrations, it is possible to compute several parameters like the response and lag of accommodation. The ocular aberrations were measured in 4 subjects, with different accommodative disorders, during several cycles of accommodation/disaccommodation and for different accommodative stimuli. The measurement was done continuously and in real time during different accommodative stimuli. It was possible to see the changes in accommodative response during the several stimuli of accommodation. Subjects with accommodative disorders showed different accommodative responses. The use of wavefront ocular aberrations can be a tool to diagnose accommodative disorders. In some subjects with complaints, this method showed irregularities even when the results of the usual clinical exams were normal. PMID- 29789804 TI - Health Risk Behaviour among Adolescents Living with HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis. AB - The burden of health risk behaviour (HRB) among adolescents living with HIV (ALWHIV) in sub-Saharan Africa (SSA) is currently unknown. A systematic search for publications on HRB among ALWHIV in SSA was conducted in PubMed, Embase, PsycINFO, and Applied Social Sciences Index and Abstracts databases. Results were summarized following PRISMA guidelines for systematic reviews and meta-analyses. Heterogeneity was assessed by the DerSimonian and Laird method and the pooled estimates were computed. Prevalence of current condom nonuse behaviour was at 59.8% (95% CI: 47.9-71.3%), risky sexual partnerships at 32.9% (95% CI: 15.4 53.2%), transactional sex at 20.1% (95% CI: 9.2-33.8%), and the experience of sexual violence at 21.4% (95% CI: 16.3-27.0%) among ALWHIV. From this meta analysis, we did not find statistically significant differences in pooled estimates of HRB prevalence between ALWHIV and HIV uninfected adolescents. However, there was mixed evidence on the occurrence of alcohol and drug use behaviour. Overall, we found that research on HRB among ALWHIV tends to focus on behaviour specific to sexual risk. With such a high burden of HRB for the individuals as well as society, these findings highlight an unmet need for age appropriate interventions to address the behavioural needs of these adolescents. PMID- 29789808 TI - The Value of 18F-FDG PET/CT Mathematical Prediction Model in Diagnosis of Solitary Pulmonary Nodules. AB - Purpose: To establish an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) mathematical prediction model to improve the diagnosis of solitary pulmonary nodules (SPNs). Materials and Methods: We retrospectively reviewed 177 consecutive patients who underwent 18F-FDG PET/CT for evaluation of SPNs. The mathematical model was established by logistic regression analysis. The diagnostic capabilities of the model were calculated, and the areas under the receiver operating characteristic curve (AUC) were compared with Mayo and VA model. Results: The mathematical model was y = exp?(x)/[1 + exp?(x)], x = -7.363 + 0.079 * age + 1.900 * lobulation + 1.024 * vascular convergence + 1.530 * pleural retraction + 0.359 * the maximum of standardized uptake value (SUVmax). When the cut-off value was set at 0.56, the sensitivity, specificity, and accuracy of our model were 86.55%, 74.14%, and 81.4%, respectively. The area under the receiver operating characteristic curve (AUC) of our model was 0.903 (95% confidence interval (CI): 0.860 to 0.946). The AUC of our model was greater than that of the Mayo model, the VA model, and PET (P < 0.05) and has no difference with that of PET/CT (P > 0.05). Conclusion: The mathematical predictive model has high accuracy in estimating the malignant probability of patients with SPNs. PMID- 29789810 TI - RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia. AB - The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization (LTS) training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naive animals. Thus, the behavioral, and a subset of the cellular, modifications characteristic of a form of nonassociative long-term memory (LTM) in Aplysia can be transferred by RNA. These results indicate that RNA is sufficient to generate an engram for LTS in Aplysia and are consistent with the hypothesis that RNA-induced epigenetic changes underlie memory storage in Aplysia. PMID- 29789809 TI - Development of Step-Count Cut Points for School-Day Vigorous Physical Activity. AB - Background: No study has established step-count cut points for varying amounts of accelerometer-assessed vigorous physical activity (VPA) accrued during the school day in children. The purpose of this study was to establish step-count cut points for discriminating children meeting VPA in 5 minutes, 10 minutes, 15 minutes, and 20 minutes per 7-hour school day. Methods: Participants were a convenience sample of 1,053 children (mean age = 8.4 (1.8) years) recruited from 5 schools from the Mountain West region of the USA. Data within students were observed across multiple semesters totaling 2,119 separate observations. Step counts and time in VPA were assessed using ActiGraph wGT3X-BT triaxial accelerometers that were worn during the entirety of a 7-hour school day for one school week. Average censored step counts and minutes in VPA were calculated across 3 to 5 days. Receiver operating characteristic (ROC) curves were employed to derive step counts via calculation of the maximum Youden J statistic. Results: Area-under-the-curve (AUC) scores ranged from AUC = 0.81 (95% CI: 0.78-0.83; p < 0.001) for meeting at least 5 minutes of VPA to AUC = 0.94 (95% CI: 0.88-1.00, p < 0.001) for meeting at least 20 minutes of VPA. Approximately 3,460 steps best discriminated children meeting at least 5 minutes of VPA (sensitivity = 74.0%, specificity = 74.0%, and accuracy = 74.1%) and approximately 5,628 steps best discriminated children meeting at least 20 minutes per day of VPA (sensitivity = 85.7%, specificity = 95.1%, and accuracy = 95.1%). Conclusion: Step counts can discriminate with reasonable accuracy children that meet at least 5 minutes of school-day VPA and with strong accuracy children that meet 20 minutes of school-day VPA. PMID- 29789812 TI - Cannabis and the Opioid Crisis. PMID- 29789811 TI - Uncovering Neuronal Networks Defined by Consistent Between-Neuron Spike Timing from Neuronal Spike Recordings. AB - It is widely assumed that distributed neuronal networks are fundamental to the functioning of the brain. Consistent spike timing between neurons is thought to be one of the key principles for the formation of these networks. This can involve synchronous spiking or spiking with time delays, forming spike sequences when the order of spiking is consistent. Finding networks defined by their sequence of time-shifted spikes, denoted here as spike timing networks, is a tremendous challenge. As neurons can participate in multiple spike sequences at multiple between-spike time delays, the possible complexity of networks is prohibitively large. We present a novel approach that is capable of (1) extracting spike timing networks regardless of their sequence complexity, and (2) that describes their spiking sequences with high temporal precision. We achieve this by decomposing frequency-transformed neuronal spiking into separate networks, characterizing each network's spike sequence by a time delay per neuron, forming a spike sequence timeline. These networks provide a detailed template for an investigation of the experimental relevance of their spike sequences. Using simulated spike timing networks, we show network extraction is robust to spiking noise, spike timing jitter, and partial occurrences of the involved spike sequences. Using rat multineuron recordings, we demonstrate the approach is capable of revealing real spike timing networks with sub-millisecond temporal precision. By uncovering spike timing networks, the prevalence, structure, and function of complex spike sequences can be investigated in greater detail, allowing us to gain a better understanding of their role in neuronal functioning. PMID- 29789813 TI - Cannabis for the Management of Cancer Symptoms: THC Version 2.0? PMID- 29789814 TI - Endolymphatic Ethiodized Oil Intranodal Lymphangiography and Cyanoacrylate Glue Embolization for the Treatment of Postoperative Lymphatic Leak After Robot Assisted Laparoscopic Pelvic Resection. AB - Purpose: To report the approach, technical success, clinical outcomes, complications, and follow-up of ethiodized oil intranodal lymphangiography with cyanoacrylate glue embolization for the treatment of lymphatic leak after robot assisted laparoscopic pelvic resection. Materials and Methods: Four men with mean age 68.7 +/- 14.3 years were treated with ethiodized oil intranodal lymphangiography with cyanoacrylate embolization for postoperative lymphatic leak. Patients underwent either (1) cystoprostatectomy with ileal conduit and bilateral extensive pelvic lymph node dissection for muscle-invasive urothelial carcinoma and presented with postoperative lymphatic ascites (n = 2) or (2) prostatectomy with bilateral standard pelvic lymph node dissection for prostate carcinoma and presented with postoperative pelvic lymphoceles (n = 2). Intranodal lymphangiography and embolization procedural details, technical success, clinical outcomes, and follow-up were recorded. Results: In four patients, a total of six ethiodized oil intranodal lymphangiograms were performed, two procedures being repeated interventions. Inguinal lymph node catheterization and ethiodized oil lymphangiography was technically effective in all procedures. A mean of 5.2 +/- 2.0 mL of ethiodized oil was used for lymphatic opacification. Cyanoacrylate was diluted to 24.2% with ethiodized oil and 0.44 mL of cyanoacrylate was instilled during first time interventions. On repeat procedures, cyanoacrylate was diluted to 51.7%, and 0.52 mL was instilled. The primary clinical success rate was 50% (n = 2/4). Clinical success was achieved in all patients after two interventions (n = 4; 100%). No complications were reported at mean follow-up of 134.7 +/- 79.2 days (range: 59-248 days). Conclusion: Ethiodized oil intranodal lymphangiography with direct cyanoacrylate glue embolization is a minimally invasive treatment option for lymphatic leak after pelvic resection. PMID- 29789815 TI - Challenging Case: Robot-Assisted Laparoscopic Prostatectomy After Prior Suprapubic Open Prostatectomy. AB - Introduction: Given the ubiquity of robot-assisted laparoscopic prostatectomy (RALP) for treatment of localized prostate cancer, more surgeons are encountering challenging cases, either secondary to difficult anatomy, prior abdominal surgery, or prior radiation therapy. Our case is of RALP in a patient after prior suprapubic prostatectomy. Case Presentation: A 61-year-old otherwise healthy Hispanic gentleman presented for consultation after being found to have Gleason 4 + 4 = 8 prostate cancer on transrectal ultrasound-guided biopsy by an outside provider in July 2017. He had previously undergone suprapubic simple prostatectomy for benign prostatic hyperplasia (BPH) in Nicaragua more than a decade prior. The patient underwent RALP with bilateral nerve sparing in September 2017. The surgery was challenging in that extensive lysis of adhesions had to be performed and typical dissecting planes at the bladder neck and apex were distorted, insofar as meticulous care was taken to judiciously use thermal energy and rely on blunt dissection at these critical junctures. That being said, there were no operative or postoperative complications, the patient was discharged on postoperative day 1, and at 3-month follow-up, the patient was fully continent, maintained erections adequate for sexual intercourse, and had a prostate specific antigen <0.1. Pathology report returned Gleason 3 + 3 = 6 disease with negative surgical margins. Discussion: There is only one other example in the literature of RALP being performed after prior suprapubic prostatectomy. Our large RALP case volume (>5000 patients for a single surgeon and counting) provided us with the necessary experience required for encountering atypical anatomy, and thereby contributed to our patient's effective surgical outcome, both oncologic and functional. Conclusion: RALP for treatment of prostate cancer is a safe and appropriate option in men who have previously undergone suprapubic open prostatectomy for BPH, especially in the hands of an experienced surgeon. PMID- 29789816 TI - An anionic sod-type terbium-MOF with extra-large cavities for effective anthocyanin extraction and methyl viologen detection. AB - An anionic sod-type zeolitic metal-organic framework [(CH3)2NH2]9{Tb6(eta6 TATAT)4(H2O)12}.3Cl.DMA.7H2O [1, H6TATAT = 5,5',5''-(1,3,5-triazine-2,4,6 triyltriimino)tri-1,3-benzenedicarboxylic acid] has been synthesized by metal ligand directed assembly of hexacarboxylic acid units and Tb3+ ions. Compound 1 with extra-large cavities can efficiently extract natural product anthocyanins from blackberries and release them rapidly into NaCl aqueous solution. And, the nature of the anionic framework makes it very sensitive to detect cationic methyl viologen (MV2+) with a detection limit as low as 1 * 10-8 M. PMID- 29789817 TI - SO2 absorption in EmimCl-TEG deep eutectic solvents. AB - Deep eutectic solvents (DESs) based on 1-ethyl-3-methylimidazolium chloride (EmimCl) and triethylene glycol (TEG) with different molar ratios (from 6 : 1 to 1 : 1) were prepared. FTIR and theoretical calculation indicated that the C2-H on the imidazolium ring form hydrogen bonds with the hydroxyl group rather than the ether O atom of the TEG. The EmimCl-TEG DESs can efficiently capture SO2; in particular, EmimCl-TEG (6 : 1) can capture 0.54 g SO2 per gram of solvent at 0.10 atm and 20 degrees C, the highest absorption amount for DESs under the same conditions. Theoretical calculation showed that the high SO2 absorption capacity was mainly due to the strong charge-transfer interaction between SO2 and the anion Cl-. Moreover, SO2 desorption in the DESs can be controlled by tuning the interaction between EmimCl and TEG, and the DESs can be cycled many times. PMID- 29789818 TI - The effect of hydration on the electronic structure and stability of the superalkali cation Li3. AB - The interaction of the superalkali cation Li3+ with water molecules, as well as the structures and stability of the resulting water complexes are theoretically studied at the MP2/6-311++G(d,p) level. A great number of geometrical configurations were obtained for the Li3+(H2O)n (n = 1-5) complexes and Li3+ is found to have a maximum coordination number of four. Natural population analysis shows that the charge distribution of Li3+ becomes seriously uneven upon interaction with five water molecules, so it loses ring conjugation and splits in the lowest-energy isomer of Li3+(H2O)5. Localized molecular orbital energy decomposition analysis indicates a dominant contribution of electrostatic interactions to the binding of water molecules to Li3+, which is similar to the case of lithium ion hydrates. However, as the number of water ligands reaches five, the contribution of the exchange-repulsion energy exhibits a sharp increase and even exceeds that of the electrostatic term. PMID- 29789819 TI - Exploring the cellular uptake and localisation of phosphorescent rhenium fac tricarbonyl metallosurfactants as a function of lipophilicity. AB - A systematic study of the cellular uptake of emissive complexes as a function of their lipophilicity is presented. Here a series of amphiphilic rhenium fac tricarbonyl bisimine complexes bearing axial substituted imidazole or thiazole ligands, [Re(bpy)(CO)3(ImCnHm)]+ {n = 1 m = 3 (1+), n = 4 m = 9 (2+), n = 8 m = 17 (3+), n = 12 m = 25 (4+), n = 16 m = 33 (5+), n = 2 m = 3 (6+); bpy = 2,2' bipyridine, Im = imidazole} and [Re(bpy)(CO)3(L)]+ {L = 1-mesitylimidazole, ImMes (7+), 4,5-dimethylthiazole, dmt (8+) and 4-methyl-5-thiazole-ethanol, mte (9+)} is reported. The X-ray crystal structures of 2+, 8+ and 9+ confirm the geometry and expected distribution of ligands and indicated that the plane of the imidazole/thiazole ring is approximately parallel to the long axis of the bipy ligand. Luminescence studies revealed excellent properties for their use in cell imaging with visible excitation and broad emission profiles. Their uptake in two distinct species has been examined by fluorescence imaging of the diplomonad fish parasite Spironucleus vortens (S. vortens) and rod-shaped yeast Schizosaccharomyces pombe (Schiz. pombe) as a function of their lipophilicity. The uptake of the complexes was highest for the more lipophilic 2+-5+ in both S. vortens and Schiz. pombe in which the long alkyl chain aids in crossing bilipid membranes. However, the increased lipophilicity of longer chains also resulted in greater toxicity. Localisation over the whole cell varied with differing alkyl chain lengths with complex 2+ preferentially locating to the nucleus of S. vortens, 3+ showing enhanced nuclear partitioning in Schiz. pombe, and 4+ for the remaining cell wall bound in the case of S. vortens. Interestingly, complexes of intermediate lipophilicity such as 7+ and 8+ showed reasonable uptake, proved to be non-toxic, and were capable of crossing exterior cell walls and localising in the organelles of the cells. PMID- 29789820 TI - Structural mechanisms of oligomer and amyloid fibril formation by the prion protein. AB - Misfolding and aggregation of the prion protein is responsible for multiple neurodegenerative diseases. Works from several laboratories on folding of both the WT and multiple pathogenic mutant variants of the prion protein have identified several structurally dissimilar intermediates, which might be potential precursors to misfolding and aggregation. The misfolded aggregates themselves are morphologically distinct, critically dependent on the solution conditions under which they are prepared, but always beta-sheet rich. Despite the lack of an atomic resolution structure of the infectious pathogenic agent in prion diseases, several low resolution models have identified the beta-sheet rich core of the aggregates formed in vitro, to lie in the alpha2-alpha3 subdomain of the prion protein, albeit with local stabilities that vary with the type of aggregate. This feature article describes recent advances in the investigation of in vitro prion protein aggregation using multiple spectroscopic probes, with particular focus on (1) identifying aggregation-prone conformations of the monomeric protein, (2) conditions which trigger misfolding and oligomerization, (3) the mechanism of misfolding and aggregation, and (4) the structure of the misfolded intermediates and final aggregates. PMID- 29789821 TI - A supramolecular photosensitizer system based on the host-guest complexation between water-soluble pillar[6]arene and methylene blue for durable photodynamic therapy. AB - A supramolecular photosensitizer system WP6-MB was synthesized based on water soluble pillar[6]arene and the photosensitizer methylene blue (MB) via host-guest interaction. MB can complex with WP6 directly with a high complex constant without further modification. In particular, WP6-MB can reduce the dark toxicity of MB remarkably. Furthermore, it can efficiently overcome photobleaching and extend the time for singlet oxygen production of MB upon light irradiation, which is significant for durable photodynamic therapy. PMID- 29789822 TI - Inhibitory effects of catechins on beta-carbolines in tea leaves and chemical model systems. AB - The profile of 18 heterocyclic amines from seven categories (including beta carbolines) in tea leaves during green and black tea processing procedures, as well as commercial tea products was screened by ultrahigh-performance liquid chromatography with tandem mass spectrometry. 2-Amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) were detected in samples; however, the levels were too low for quantification. The beta carboline compounds harman and norharman were quantified in all the samples. During processing, both harman and norharman levels increased significantly (p < 0.01) with the highest levels present in tea leaves during the rolling stage of green tea processing and the drying stage of black tea processing. In commercial products, the highest levels of harman and norharman were found in black tea as 31.49 +/- 3.21 and 59.68 +/- 4.71 ng g-1 sample, respectively. In combination with the catechin levels of tea leaves and the results of chemical model systems, it was demonstrated that ECG, EGC, and EGCG could significantly (p < 0.01) inhibit the formation of harman and norharman by up to 45% and 52%, respectively. PMID- 29789823 TI - Influenza A M2 transmembrane domain tunes its conformational heterogeneity and structural plasticity in the lipid bilayer by forming loop structures. AB - We discovered for the first time that the influenza A virus M2TM tunes its conformational heterogeneity and structural plasticity to respond to environmental cues by undergoing a helix-to-loop transition, resolving controversies regarding the mechanism of proton conduction and plasticity of the M2TM in lipid bilayers. PMID- 29789825 TI - Highly active aluminium catalysts for room temperature ring-opening polymerisation of rac-lactide. AB - A new series of aluminium complexes bearing 'catam' ligands has been synthesised and fully characterised. They were found to exhibit high activity at room temperature for rac-lactide ring-opening polymerisation, a rather rare feature for aluminium-based catalysts. PMID- 29789824 TI - Layered double hydroxide/poly-dopamine composite coating with surface heparinization on Mg alloys: improved anticorrosion, endothelialization and hemocompatibility. AB - Magnesium (Mg) and its alloys are promising cardiovascular stent materials due to their favourable physical properties and complete degradation in vivo. However, rapid degradation and poor cytocompatibility hinder their clinical applications. To enhance the corrosion resistance and endothelialization of the AZ31 alloy, a layered double hydroxide (LDH)/poly-dopamine (PDA) composite coating (LDH/PDA) was successfully fabricated. Polarization curves and the electrochemical impedance spectroscopy Nyquist spectrum test proved that the corrosion resistance of the LDH/PDA sample was significantly improved in vitro. The LDH/PDA sample greatly improved the adherence process and the proliferation rate of human umbilical vein endothelial cells (HUVECs). After culturing for 10 days, the number of living HUVECs on the LDH/PDA sample was comparable to that on the Ti sample whereas the cells barely survived on the AZ31 or LDH coating. Furthermore, heparin was immobilized on LDH/PDA via a covalent bond (LDH/PDA/HEP). The corrosion resistance and long-term proliferation of HUVECs after the introduction of heparin were mildly decreased compared with the L/P sample, but were still greatly improved compared with AZ31, the LDH coating and the PDA coating. Furthermore, the LDH/PDA/HEP sample greatly improved the HUVEC migration rate compared with the LDH/PDA sample, and inhibited platelet adhesion which was intense on the LDH/PDA sample. Both LDH/PDA and LDH/PDA/HEP samples had a low hemolysis rate (2.52% and 0.65%, respectively) in vitro and eliminated the adverse biocompatible effects of the direct PDA coating on the AZ31 substrate in vivo. Our results suggest that the LDH/PDA composite coating with further heparinization is a promising method to modify the surface of Mg alloys by significantly improving corrosion resistance, endothelialization and hemocompatibility. PMID- 29789826 TI - Structural, optoelectronic and charge transport properties of the complexes of indigo encapsulated in carbon nanotubes. AB - Using the dispersion-corrected density functional B97D and 6-31g(d,p) basis set, the structural, stability, electronic, optical and charge transport properties of the complexes formed by encapsulating indigo inside carbon nanotubes (CNTs) of varying diameters are investigated. Based on the stabilization energy of the complexes indigo@(n,n)CNT (where n = 6, 7 and 8), indigo@(7,7)CNT is shown to be the most stable owing to the ideal diameter of (7,7)CNT for encapsulating indigo. The nature of the interaction between the guest and the host is investigated by means of energy decomposition analysis employing the symmetry adapted perturbation theory. Electronic properties such as the ionization energy, the electron affinity and the energy gap between the highest occupied and lowest unoccupied molecular orbitals (DeltaEH-L) of the complexes are determined. The low values of DeltaEH-L (<1 eV) for the complexes suggest that they can act as narrow energy gap semiconductors. All the complexes exhibit high hole and electron mobilities which vary inversely with respect to the diameter of the CNT. Using the time-dependent density functional theoretical method, the absorption properties are predicted for the most stable complex indigo@(7,7)CNT. The presence of charge transfer peaks in the visible and near-infrared regions of the electromagnetic spectrum suggests that the complexes are suitable for optoelectronic devices such as solar cells. PMID- 29789827 TI - Effect of the monostearate/monopalmitate ratio on the oral release of active agents from monoacylglycerol organogels. AB - The delivery of active agents from organogels is becoming an important topic owing to the possibility of releasing, in a controlled way, lipophilic agents. Controlled release from foods is a topic with increasing relevance owing to the growing industrial interest towards functional or medical foods, i.e. foods containing nutraceutical agents or drugs. Anyway, release properties are related to the rheological properties of organogels, and, therefore, a deep knowledge of their microstructure and physical characteristics is necessary to design carriers with expected release properties. In this work, two low molecular weight gelators (i.e. glycerol monopalmitate, GMP, and glycerol monostearate, GMS) have been investigated using rheology, microscopy and infrared spectroscopy, IR, aiming at understanding the effects of different gelator ratios on organogel properties. It was observed that GMP, within the range of investigated compositions, seems to be more effective in yielding consistent organogels and this effect was related to differences in microstructure with respect to GMS. Their ability to control the oral release of active agents was investigated, in vitro, using a chemotherapeutic drug for adenocarcinoma of the gastrointestinal tract, 5 fluorouracil (5-FU). A physical model based on carrier erosion was used to describe the release data, evidencing a good agreement with experimental values. Among the tested samples it seems that the use of 90% of GMS (over total organogelator content) yields promising results allowing a good partition of the released drug between the gastric and intestinal tracts with the largest value (although lower than 40% of loaded amount) of the total released drug. PMID- 29789828 TI - Unravelling the spin-state of solvated [Fe(bpp)2]2+ spin-crossover complexes: structure-function relationship. AB - This paper reports firstly the syntheses, crystal structures, and thermal and magnetic properties of spin crossover salts of formulae [Fe(bpp)2]3[Cr(CN)6]2.13H2O (1) and [Fe(bpp)2][N(CN)2]2.H2O (2) (bpp = 2,6 bis(pyrazol-3-yl)pyridine) exhibiting hydrogen-bonded networks of low-spin [Fe(bpp)2]2+ complexes and [Cr(CN)6]3- or [N(CN)2]- anions, with solvent molecules located in the voids. Desolvation of 1 is accompanied by a complete low spin (LS) to a high-spin (HS) transformation that becomes reversible after rehydration by exposing the sample to the humidity of air. The influence of the lattice water on the magnetic properties of spin-crossover [Fe(bpp)2]X2 complex salts has been documented. In most cases, it stabilises the LS state over the HS one. In other cases, it is rather the contrary. The second part of this paper is devoted to unravelling the reasons why the lattice solvent stabilises one form over the other through magneto-structural correlations of [Fe(bpp)2]2+ salts bearing anions with different charge/size ratios (Xn-). The [Fe(bpp)2]2+ stacking explaining these two different behaviours is correlated here with the composition of the second coordination sphere of the Fe centers and the ability of these anions to form hydrogen bonds and/or pi-pi stacking interactions between them or the bpp ligand. PMID- 29789829 TI - Amplified spontaneous emission in phenylethylammonium methylammonium lead iodide quasi-2D perovskites. AB - Organo-metal-halide perovskites are a promising set of materials for optoelectronic applications such as solar cells, light emitting diodes and lasers. Perovskite thin films have demonstrated amplified spontaneous emission thresholds as low as 1.6 MUJ cm-2 and lasing thresholds as low as 0.2 MUJ cm-2. Recently the performance of perovskite light emitting diodes has rapidly risen due to the formation of quasi 2D films using bulky ligands such as phenylethylammonium. Despite the high photoluminescent yield and external quantum efficiency of quasi 2D perovskites, few reports exist on amplified spontaneous emission. We show within this report that the threshold for amplified spontaneous emission of quasi 2D perovskite films increases with the concentration of phenylethylammonium. We attribute this increasing threshold to a charge transfer state at the PEA interface that competes for excitons with the ASE process. Additionally, the comparatively slow inter-grain charge transfer process cannot significantly contribute to the fast radiative recombination in amplified spontaneous emission. These results suggest that relatively low order PEA based perovskite films that are suitable for LED applications are not well suited for lasing applications. However high order films were able to maintain their low threshold values and may still benefit from improved stability. PMID- 29789830 TI - Anomalous strength characteristics of Stone-Thrower-Wales defects in graphene sheets - a molecular dynamics study. AB - Graphene, viz., the one-atom-thick sheet of carbon, exhibits outstanding mechanical properties, but defects, which are inevitable at the time of synthesis, may strongly affect these properties. In this study, the effects of two types of Stone-Thrower-Wales (namely, STW-1 and STW-2) defects on the mechanical properties of graphene sheets at different temperatures and strain rates were investigated on the basis of molecular dynamics simulations. The authors also investigated the effect of the strain rate and defect concentration on the failure morphology of STW-1 and STW-2 defected graphene sheets. It was observed that, irrespective of the strain rate, the fracture strengths of STW-1 and STW-2 defected graphene sheets are identical in the zigzag and armchair directions, respectively, at low temperatures. It was also observed that the fracture strengths of graphene sheets with STW-1 defects in the armchair direction and STW-2 defects in the zigzag direction decrease drastically at higher temperatures and also at lower strain rates. On the other hand, it was noticed that the fracture strengths of graphene sheets with STW-1 defects in the zigzag direction and STW-2 defects in the armchair direction decrease gradually with an increase in the temperature and a decrease in the strain rate. It was also predicted that the failure morphology of graphene sheets with STW-1 defects in the zigzag direction and STW-2 defects in the armchair direction depends on the defect concentration and the strain rate. PMID- 29789831 TI - A new structure family of oxide-ion conductors Ca0.8Y2.4Sn0.8O6 discovered by a combined technique of the bond-valence method and experiments. AB - Mg3TeO6-type Ca0.8Y2.4Sn0.8O6 has been found as a new structure family of oxide ion conductors. From bond-valence-based energy (BVE) calculations for 147 compositions, which contain tin (Sn) as an essential element, Mg3TeO6-type Ca0.8Y2.4Sn0.8O6 was found to have a low energy barrier for oxide-ion migration. Ca0.8Y2.4Sn0.8O6 was synthesized by the solid-state reaction, and its electrical conductivity and crystal structure were investigated. The total electrical conductivity at various partial oxygen pressures and band gap estimated from the UV-vis spectrum suggested that Ca0.8Y2.4Sn0.8O6 is a pure oxide-ion conductor. The activation energy for the oxide-ion conductivity of Ca0.8Y2.4Sn0.8O6 was 1.39(4) eV. Synchrotron X-ray powder diffraction data of Ca0.8Y2.4Sn0.8O6 at 300 and 1273 K were successfully analyzed with the Mg3TeO6-type structure. The BVE calculation using the refined crystal structure of Ca0.8Y2.4Sn0.8O6 at 1273 K strongly suggested three dimensional oxide-ion diffusion. PMID- 29789832 TI - Photocatalytic chemoselective cleavage of C-O bonds under hydrogen gas- and acid free conditions. AB - In the presence of a palladium-loaded TiO2 photocatalyst, the cleavage of benzyl phenyl ether in low-molecular-weight alcohol solvents under de-aerated conditions afforded toluene and phenol simultaneously in a 1 : 1 molar ratio. PMID- 29789833 TI - Zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration. AB - A novel zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration has been developed, which represents the first example of a non-noble metal-catalyzed reaction between isoxazoles and alkynes. This method allows the facile and atom-economical synthesis of a range of valuable beta-keto enamides. Moreover, the computational study provides further evidence for the feasibility of the proposed reaction mechanism. PMID- 29789834 TI - Time programmable hydrogels: regulating the onset time of network dissociation by a reaction relay. AB - Biological networks are capable of programming temporal evolution of their crosslinking and dissociation reactions. However, replicating this feature in synthetic self-assemblies is challenging. Herein we report the design of dynamic polymeric hydrogels that undergo delayed dissociation with an onset time precisely tuned from minutes to hours by a reaction relay. PMID- 29789835 TI - Insights into the complex interaction between hydrophilic nanoparticles and ionic surfactants at the liquid/air interface. AB - Combinations of nanoparticles and surfactants have been widely employed in many industrial processes, i.e., boiling and condensation in heat transfer and hydraulic fracturing in shale oil and gas production, etc. However, the underlying mechanism for various phenomena resulting from the addition of nanoparticles into the surfactant solutions is still unclear. For instance, there are contradictory conclusions from the literature regarding the variations of surface tension upon the addition of nanoparticles into surfactant solutions. In this work, the dominating factors determining if the surface activity of the surfactant solution will increase or conversely decrease when adding certain kinds of nanoparticles have been investigated. Two typical hydrophilic nanoparticles, SiO2 and TiO2 with anionic or cationic surfactants, respectively, have been considered. The surface tension has been measured in a wide range of nanoparticle and surfactant concentrations. It was found that the surface tension of the ionic surfactant solution can be further reduced only if nanoparticles of the same charge were added. For instance, a system containing 0.25 CMC SDS and 1 wt% SiO2 behaves similar to a 0.34 CMC SDS-only solution. Interestingly, the observed synergistic effect is found to be more significant if the surfactant concentration is much lower than its CMC for a given nanoparticle content. Moreover, the effect is perfectly reversible. When the nanoparticles were separated from the system, the surface tension values recovered fully to that of the pure surfactants. If nanoparticles of opposite charge were added, however, the surface tension of the surfactant solution increased. Zeta potential measurement and centrifugal treatment have been employed to reveal the interplay between nanoparticles and surfactants and the adsorption behavior of their assemblies at the liquid/air interface. Based on the experimental outcomes, a possible physical mechanism was proposed. It was concluded that the electrostatic repulsion between surfactant molecules and nanoparticles should be the dominant factor responsible for the observed reversible synergistic effect. Our study is expected to contribute to a better understanding of the interfacial phenomenon in nanoparticle-surfactant complex systems. PMID- 29789836 TI - Lithium effect on the electronic properties of porous silicon for energy storage applications: a DFT study. AB - Theoretical studies on the effect of Li on the electronic properties of porous silicon are still scarce; these studies could help us in the development of Li ion batteries of this material which overcomes some limitations that bulk silicon has. In this work, the effect of interstitial and surface Li on the electronic properties of porous Si is studied using the first-principles density functional theory approach and the generalised gradient approximation. The pores are modeled by removing columns of atoms of an otherwise perfect Si crystal, dangling bonds of all surfaces are passivated with H atoms, and then Li is inserted on interstitial positions on the pore wall and compared with the replacement of H atoms with Li. The results show that the interstitial Li creates effects similar to n-type doping where the Fermi level is shifted towards the conduction band with band crossings of the said level thus acquiring metallic characteristics. The surface Li introduces trap-like states in the electronic band structures which increase as the number of Li atom increases with a tendency to become metallic. These results could be important for the application of porous Si nanostructures in Li-ion batteries technology. PMID- 29789837 TI - Size effects on rhodium nanoparticles related to hydrogen-storage capability. AB - To unveil the origin of the hydrogen-storage properties of rhodium nanoparticles (Rh NPs), we investigated the electronic and crystal structures of the Rh NPs using various synchrotron based X-ray techniques. Electronic structure studies revealed that the hydrogen-storage capability of Rh NPs could be attributed to their more unoccupied d-DOSs than that of the bulk near the Fermi level. Crystal structure studies indicated that lattice distortion and mean-square displacement increase while coordination number decreases with decreasing particle size and the hydrogen-absorption capability of Rh NPs improves to a greater extent with increased structural disorder in the local structure than with that in the mean structure. The smallest Rh NPs, having the largest structural disorder/increased vacancy spaces and the smallest coordination number, exhibited excellent hydrogen storage capacity. Finally, from the bond-orientational order analysis, we confirmed that the localized disordering is distributed more over the surface part than the core part and hydrogen can be trapped on the surface part of Rh NPs which increases with a decrease in NP diameter. PMID- 29789838 TI - Elastomeric microvalve geometry affects haemocompatibility. AB - This paper reports on the parameters that determine the haemocompatibility of elastomeric microvalves for blood handling in microfluidic systems. Using a comprehensive investigation of blood function, we describe a hierarchy of haemocompatibility as a function of microvalve geometry and identify a "normally closed" v-gate pneumatic microvalve design that minimally affects blood plasma fibrinogen and von Willebrand factor composition, minimises effects on erythrocyte structure and function, and limits effects on platelet activation and aggregation, while facilitating rapid switching control for blood sample delivery. We propose that the haemodynamic profile of valve gate geometries is a significant determinant of platelet-dependent biofouling and haemocompatibility. Overall our findings suggest that modification of microvalve gate geometry and consequently haemodynamic profile can improve haemocompatibility, while minimising the requirement for chemical or protein modification of microfluidic surfaces. This biological insight and approach may be harnessed to inform future haemocompatible microfluidic valve and component design, and is an advance towards lab-on-chip automation for blood based diagnostic systems. PMID- 29789839 TI - A cocktail of 165Er(iii) and Gd(iii) complexes for quantitative detection of zinc using SPECT and MRI. AB - We propose quantitative assessment of zinc by combining nuclear and MR imaging. We use a cocktail of a Gd3+-complex providing a Zn2+-dependent MRI response and its 165Er3+ analogue allowing for concentration assessment. 165Er is readily obtained in a cyclotron and purified, which is indispensable for successful quantification of metal ions. PMID- 29789840 TI - Prominent hydrogenation catalysis of a PVP-stabilized Au34 superatom provided by doping a single Rh atom. AB - A single rhodium atom was precisely doped into a gold cluster Au34 stabilized by poly(N-vinyl-2-pyrrolidone) (Au:PVP) as revealed by mass spectrometry. The Rh atom-doped Au:PVP exhibited remarkable catalytic activity for hydrogenation reactions of olefins, which was much higher than that of recently reported Pd atom-doped Au:PVP. PMID- 29789841 TI - F-Doping effects on carbon-coated Li3V2(PO4)3 as a cathode for high performance lithium rechargeable batteries: combined experimental and DFT studies. AB - F-Doping effects on polyaniline-derived carbon coated Li3V2(PO4)3 (Li3V2(PO4)3 xFx@C) as a cathode for high performance Li rechargeable batteries are systematically investigated with a combined experimental and DFT theoretical calculation approach. The results clearly indicate that the doping amount has a significant impact on the rate capability and long cycle life. The optimal material (Li3V2(PO4)2.88F0.12@C) delivers 123.16 mA h g-1@2C, which is close to the theoretical value (133 mA h g-1), while showing a greatly improved cycle stability. Rietveld refinements show that the F- doping does not obey Vegard's Law, which may be attributed to the generated lower valence of V ions. AC impedance spectroscopy shows that the F-doping can achieve faster interfacial charge transfer for higher reaction reversibility. DFT calculations confirm that the lower V2+ (t2g?)3 does exist in Li3V2(PO4)2.88F0.12, and the mean nearest neighbor Li-O bond length also increases for faster electrochemical kinetics, and further reveal that there is a tendency for a transition from the insulator to the n-type semiconductor due to the F dopant. The combined experimental and calculated results suggest that F-doping indeed greatly facilitates the charge transfer rate of the Li+ insertion/de-insertion process for better reversibility and enhances the Li+ diffusion rate to access the reaction sites, thus resulting in high rate capacity and cycling stability. This work not only offers a facile and effective approach to synthesize high performance Li-ion battery material for very promising practical applications, but also discloses scientific insights on element coating and doping to guide the electrode material design for fast electrode kinetics in energy storage devices. PMID- 29789843 TI - Efficient alkaline hydrogen evolution electrocatalysis enabled by an amorphous Co Mo-B film. AB - An amorphous Co-Mo-B film on a Ti mesh (Co-Mo-B/Ti) is fabricated via one-step electrodeposition exhibiting a dramatically enhanced hydrogen evolution reaction (HER) performance in alkaline media. To attain a current density of 20 mA cm-2, such Co-Mo-B/Ti demands only an overpotential of 110 mV, 190 mV lower than that of the counterpart Co-B/Ti, with strong electrochemical durability to maintain its catalytic activity for at least 32 h. PMID- 29789842 TI - Synthesis of alpha-CF3 and alpha-CF2H amines via the aminofluorination of fluorinated alkenes. AB - A novel synthesis of alpha-CF3 and alpha-CF2H amines via the aminofluorination of gem-difluoroalkenes and mono-fluoroalkenes, respectively, is reported. The method employs Selectfluor as an electrophilic fluorine source and acetonitrile as a nitrogen source. Mechanistic studies revealed a single-electron oxidation/fluorine-abstraction/Ritter-type amination pathway. The protocol allowed the synthesis of a broad range of fluorinated amines including those bearing quaternary carbon centers with good efficiency and functional group tolerance. PMID- 29789844 TI - Fluorescence/phosphorescence-conversion in self-assembled organic microcrystals. AB - Organic molecules of DIDB can inherently assemble into fluorescent green-emissive microwires with a low photoluminescence quantum efficiency (PLQY) of 1.0%. Impressively, by doping DIDB into the nonluminous 4-iodobenzonitrile crystal matrix with a molar ratio of 1 : 100, phosphorescent yellow-emissive microwires with a much higher PLQY of 50.5% are obtained. PMID- 29789845 TI - Photoswitchable transition metal complexes with azobenzene-functionalized imine based ligands: structural and kinetic analysis. AB - We report on the characterization of two imine type ligands containing photoresponsive azobenzene units as side groups and their transition metal ions complexes. The ligands, both free and in their complexes undergo trans- > cis photoisomerization after irradiation with UV light, but binding of metal ions reduces both the photoisomerisation reaction rates and cis isomer concentrations in the photostationary states. The greatest diminution in the photoisomerisation rate was observed for the complex containing Cd(ii), the heaviest among the various transition metal ions tested in this study. PMID- 29789846 TI - Macroscopic and local approaches of phase transition in sol-gel synthesized (Bi0.5Na0.5)TiO3-SrTiO3 thin films. AB - High-quality (1 - x)(Bi0.5Na0.5)TiO3-xSrTiO3 lead-free piezoelectric thin films (x = 0, 0.1, and 0.25) on Pt(111)/Ti/SiO2/Si(100) substrates were prepared by a sol-gel method. The microstructures of the thin films as a function of SrTiO3 doping level and temperature were investigated by X-ray diffraction and Raman spectroscopy. Their temperature- and frequency-dependent piezoelectric properties were studied on the nanoscale using switching spectroscopy piezoresponse force microscopy (SS-PFM). A rhombohedral ferroelectric to pseudocubic relaxor phase transition was observed when either ST content or temperature increased. The significant frequency dependence of both ferroelectric and piezoelectric properties was also disclosed by analyzing polarization hysteresis loops on the macroscopic scale and local switching dynamics at various frequencies. It was determined that the short-range order clusters came out through the long-range ferroelectric order, thus the nanoscale approaches are consistent with macroscopic data at elevated temperatures and various frequency ranges. PMID- 29789848 TI - Enhanced field-emission properties of buckled alpha-borophene by means of Li decoration: a first-principles investigation. AB - In this study, the structures and field-emission properties of Li-decorated buckled alpha-borophene (BBP) were investigated by first-principles density functional theory at the PW91 level. Using the computed binding energies, Hirshfeld- and electrostatic potential-derived charges, induced dipole moments, densities of states, and ionization potentials, we evaluated the influence of an applied electric field on the structural stability, work function, and field emission current of the Li-decorated BBP nanostructures. Furthermore, we also explored the quantitative dependence of the emission current on the electric field, Li concentration, and molecular orbitals. The computed results indicated that increasing the electric field and Li concentration has a considerably positive effect on the field-emission performance of the Li-decorated BBPs. Besides advantages including small work functions and low ionization potentials, most remarkably, the field-emission current can be as high as 48.81 MUA in Li4/BBP (supercell with 36 atoms only) under a rather small applied electric field of 0.05 V A-1, which rivals the highest value of the graphene-BN nanocomposite among all the theoretical nanostructures presented to date. Our results highly support the fact that Li-decorated BBPs can be appealing field emission cathode materials with an extremely high emission current. PMID- 29789847 TI - Streamlined chemoenzymatic total synthesis of prioritized ganglioside cancer antigens. AB - A highly efficient streamlined chemoenzymatic strategy for total synthesis of four prioritized ganglioside cancer antigens GD2, GD3, fucosyl GM1, and GM3 from commercially available lactose and phytosphingosine is demonstrated. Lactosyl sphingosine (LacbetaSph) was chemically synthesized (on a 13 g scale), subjected to sequential one-pot multienzyme (OPME) glycosylation reactions with facile C18 cartridge purification, followed by improved acylation conditions to form target gangliosides, including fucosyl GM1 which has never been synthesized before. PMID- 29789849 TI - Synthesis, characterization and properties of aryl-fused bis-BN dihydropyrenes. AB - A series of aryl-fused bis-BN dihydropyrenes were synthesized via amino-directed borylation reaction. The aryl-fused bis-BN dihydropyrenes showed blue emission, and their physical properties could be finely tuned through varying the fused aryl rings. In particular, their response towards fluoride anions was greatly dependent on the nature of the fused aryl rings. PMID- 29789850 TI - A Ag synchronously deposited and doped TiO2 hybrid as an ultrasensitive SERS substrate: a multifunctional platform for SERS detection and photocatalytic degradation. AB - Ag simultaneously deposited and doped TiO2 (Ag-TiO2) hybrid nanoparticles (NPs) were prepared via a sol-hydrothermal method, as both a sensitive surface-enhanced Raman scattering (SERS) substrate and a superior photocatalyst for the first time. Ag-TiO2 hybrid NPs exhibit excellent SERS performance for several probe molecules and the enhancement factor is calculated to be 1.86 * 105. The detection limit of the 4-mercaptobenzoic acid (4-MBA) probe on the Ag-TiO2 substrate is 1 * 10-9 mol L-1, which is four orders of magnitude lower than that on pure TiO2 as a consequence of the synergistic effects of TiO2 and Ag. This is the highest SERS sensitivity among the reported semiconductor substrates and even comparable to noble metal substrates, and a SERS enhancement mechanism from the synergistic contribution of the semiconductor and noble metal was proposed. And importantly, the Ag-TiO2 hybrid shows excellent photocatalytic degradation activity for the detected species under UV light irradiation at lower concentration conditions, even for the hard to degrade 4-MBA molecule. This makes the Ag-TiO2 hybrid promising as a dual-function platform for both highly sensitive SERS detection and photocatalytic degradation of a pollutant system. Moreover, it also proves that the Ag-TiO2 hybrid can serve as a promising recyclable SERS-active substrate by virtue of its photocatalytic self-cleaning properties for some specific applications, for instance comparative studies of different species on the same SERS platform, in addition to the economic benefit. PMID- 29789851 TI - Atomic-scale understanding of high thermal stability of the Mo/CoFeB/MgO spin injector for spin-injection in remanence. AB - Remanent spin injection into a spin light emitting diode (spin-LED) at zero magnetic field is a prerequisite for future application of spin optoelectronics. Here, we demonstrate the remanent spin injection into GaAs based LEDs with a thermally stable Mo/CoFeB/MgO spin injector. A systematic study of magnetic properties, polarization-resolved electroluminescence (EL) and atomic-scale interfacial structures has been performed in comparison with the Ta/CoFeB/MgO spin injector. The perpendicular magnetic anisotropy (PMA) of the Mo/CoFeB/MgO injector shows more advanced thermal stability than that of the Ta/CoFeB/MgO injector and robust PMA can be maintained up to 400 degrees C annealing. The remanent circular polarization (PC) of EL from the Mo capped spin-LED reaches a maximum value of 10% after 300 degrees C annealing, and even remains at 4% after 400 degrees C annealing. In contrast, the Ta capped spin-LED almost completely loses the remanent PC under 400 degrees C annealing. Combined advanced electron microscopy and spectroscopy studies reveal that a large amount of Ta diffuses into the MgO tunneling barrier through the CoFeB layer after 400 degrees C annealing. However, the diffusion of Mo into CoFeB is limited and never reaches the MgO barrier. These findings afford a comprehensive perspective to use the highly thermally stable Mo/CoFeB/MgO spin injector for efficient electrical spin injection in remanence. PMID- 29789852 TI - Mild rhodium(iii)-catalyzed intramolecular annulation of benzamides with allylic alcohols to access azepinone derivatives. AB - Azepinone derivatives are important frameworks of several natural products and bioactive compounds. They are synthetized using a Rh(iii)-catalyzed intramolecular annulation of benzamide-tethered allylic alcohols. The reaction requires mild conditions at room temperature and affords diversely substituted azepinones bearing a quaternary carbon. PMID- 29789853 TI - Effect of oscillation dynamics on long-range electron transfer in a helical peptide monolayer. AB - Electron transfer (ET) reactions via helical peptides composed of -(Aib-Pro)n- were studied in self-assembled monolayers and compared with -(Ala-Aib)n- peptides. Short Aib-Pro peptides showed slightly higher ET rates due to the better electronic coupling of the Pro residue. But, the 24mer Aib-Pro peptide showed a smaller ET rate than the corresponding Ala-Aib peptide. On the basis of DFT calculations, the deceleration of the ET rate of the longer Aib-Pro peptide is considered to be due to the smaller number of active modes of accordion-like oscillations than the Ala-Aib peptide, which has a strong influence on a long range ET reaction. PMID- 29789854 TI - Theoretical study on the optical and electronic properties of graphene quantum dots doped with heteroatoms. AB - The effects of four heteroatoms (B, N, P, and S) with three doping patterns on graphene quantum dots (GQDs) are systematically investigated using time-dependent density functional theory (TD-DFT). The absorption spectra and HOMO-LUMO gaps are quantitatively analyzed to study the correlations between the optical properties and heteroatom doping of doped GQDs. Heteroatom doping can endow GQDs with various new optical and structural properties, depending on the dopants and doping configurations. Compared with the absorption spectra of pristine GQD, both N and S surface doping demonstrate a slight blue shift, whereas B and P doping lead to a blue shift for edge-doped GQDs with heteroatoms in a pentatomic ring. The absorption process is investigated along with excited state analysis, which includes the density of state, natural transition orbital, and charge difference density. The results indicate that large radius atoms assist charge transfer in the excited state and play an important role in recombining the electron density distribution in the doped GQDs. PMID- 29789855 TI - How Does SCORTEN Score? AB - The Toxic Epidermal Necrolysis-specific severity of illness score (SCORTEN) was developed to predict mortality in patients with Stevens Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several studies have attempted to assess the accuracy of SCORTEN with mixed results. The objective of this study is to compare the predicted and actual mortality for patients with SJS/TEN admitted to a single high-volume burn center.This retrospective study included adult and pediatric patients admitted to our burn center with biopsy-confirmed SJS/TEN between February 2008 and February 2016. SCORTEN scores were calculated for each patient on days 1 and 3 of admission. The primary endpoint was predicted vs actual in hospital mortality. Secondary endpoints included the association of SCORTEN, as well as individual components of SCORTEN, with hospital length of stay, length of stay in the intensive care unit, and in-hospital complications.Of 128 patients included, the mean age was 44.5 years, 40.6% (n = 52) were males, and 50.0% (n = 64) were Caucasians. The median TBSA was 12.25% on day 1 and 25% on day 3. The median SCORTEN at admission was 2 (interquartile range: 1-3.5). There were a total of 20 deaths (17.2%). SCORTEN exhibited good discrimination (c-statistic = 0.83, 95% CI: 0.75-0.91) and performed directionally as expected, but a low but nonsignificant standardized mortality ratio (75.3%, P = .164) and a Hosmer Lemeshow test of borderline significance (P = .088) make the model's fit unclear.The accuracy of the SCORTEN model in predicting mortality for SJS/TEN patients treated in a burn center remains unclear. This study may encourage future multicenter studies to further clarify its predictive ability and may also enhance future investigation into the use of a reformulated or reweighted SCORTEN. PMID- 29789856 TI - Impact of a Laser Service Line for Burn Scar on a Dedicated Burn OR's Flow and Productivity. AB - Our group began performing erbium-YAG 2940 wavelength fractional resurfacing of burn scar in our burn center's dedicated burn operating room (OR) in January 2016. The impact of these procedures on the performance of a mature, dedicated burn OR is unknown. All burn OR cases performed between January 1, 2015 and December 31, 2015 served as a pre-laser (PRE-LSR) historical control. A postintervention cohort of laser-only cases (LSR) performed between January 1, 2016 and August 17, 2016 was then identified. PRE-LSR and LSR cases were retrospectively reviewed for OR component times, and work relative value units (wRVU) billed. A total of 628 burn OR cases were done in 2015 (PRE-LSR), while 488 burn OR cases were done between January 1 and August 17, 2016. Of these 488, 59 cases were LSR (12.1%). Calculated on a monthly basis, significantly more cases were done per day in the LSR era (2.2 +/- 0.4 cases/d) than PRE-LSR (1.6 +/ 2.0 cases/d; P < .0001). The LSR group was significantly shorter than the PRE LSR group for all OR component times (induction, prep, and procedure all P < .0001; transport out, P = .01; room turnover, P = .004). Aggregate OR component time was 79.2 +/- 33.4 minutes for LSR and 157.5 +/- 65.0 minutes for PRE-LSR (P < .0001). LSR yielded 6.9 +/- 3.2 wRVU/h, while PRE-LSR generated 12.2 +/- 8.9 wRVU/h (P < .0001). Despite significantly shorter OR component times and more cases being done per day, laser treatment of burn scar using a single 17108 Current Procedural Terminology code cuts wRVUs generated per hour in a mature burn OR roughly in half. PMID- 29789857 TI - Ongoing Development and Evaluation of a Method of Telemedicine: Burn Care Management With a Smartphone. AB - In cases involving small burns in patients without a comorbidity or associated pathology, a referral from a surgeon is necessary and sometimes it cannot be ascertained when the patient is not brought in by a specialized team. The purpose of this retrospective study was to evaluate the quality of our method for performing telemedicine. This retrospective study included the 323 patients who were initially treated using the telemedicine system implemented between 2011 and 2016. This procedure only involved patients burned over a small portion of their body's surface area (ie, <=15%) who were between 15 and 75 years of age and who did not have a major comorbidity. The purpose of the procedure was to evaluate the need for surgery. The initial diagnosis regarding the need for a surgical procedure was accurate in 94.4% (305/323) of the cases. Eleven patients (3.4%) were transferred unnecessarily as they ultimately did not require surgery, and seven patients (2.2%) were ultimately transferred even though the need for surgery was not initially established at the time that the pictures were viewed. No initial errors in the photographic evaluation caused a worsening in the life threatening, functional, or aesthetic prognoses. We have recently opted to use telemedicine for initial patient management. In 94.4% of cases, the opinion that was provided was accurate. Only 3.2% of the patients for whom outpatient treatment was recommended ultimately underwent surgery without subsequently experiencing the slightest injury due to any delay in therapy. Although it will never replace clinical examination, these results have encouraged us to develop telemedicine based on digital photography. PMID- 29789858 TI - Correction to: Vacuum-Assisted Wound Closure with Mesh-Mediated Fascial Traction Achieves Better Outcomes than Vacuum-Assisted Wound Closure Alone: A Comparative Study. AB - In the original article the credit line for the reuse of Fig. 1 from an article published in the open access journal, World Journal of Emergency Surgery is missing. PMID- 29789859 TI - Fibrous dysplasia: an unusual case of a very aggressive form with costo-vertebral joint destruction and invasion of the contralateral D7 vertebral body. AB - Fibrous dysplasia (FD) is a benign fibro-osseous disease of the bone that may be solitary or multicentric. It is important to distinguish this type of lesion from low-grade osteosarcomas (LGOS) and from secondary sarcomas, because malignant transformation has rarely been reported. It is classically described as having a ground-glass appearance, endosteal scalloping, and thinning of the cortex. Cortical disruption is considered evidence of malignancy, but it can also be present in benign FD with aggressive behavior. We present an unusual case of aggressive FD of the 7th left rib, already diagnosed more than 22 years ago, where cortical and costo-vertebral joint disruption and 7th thoracic vertebral body involvement were not evidence of malignant behavior. From a histological perspective, FD and LGOS are similar; even if histology is of fundamental importance, the diagnosis has to be made based on the clinical and radiological aspects as well, although at imaging, differentiation between FD and LGOS can be difficult. In the present case, even though the histological examination suggested a benign lesion, the radiological examination instead consistently suggests malignancy. It is for this reason that there should be a high index of suspicion during follow-up and a new biopsy should be scheduled in case any changes occur during follow-up. PMID- 29789860 TI - Gastric perforation following cardiopulmonary resuscitation. PMID- 29789861 TI - The use of echocardiographic indices in defining and assessing right ventricular systolic function in critical care research. AB - PURPOSE: Many echocardiographic indices (or methods) for assessing right ventricular (RV) function are available, but each has its strengths and limitations. In some cases, there might be discordance between the indices. We conducted a systematic review to audit the echocardiographic RV assessments in critical care research to see if a consistent pattern existed. We specifically looked into the kind and number of RV indices used, and how RV dysfunction was defined in each study. METHODS: Studies conducted in critical care settings and reported echocardiographic RV function indices from 1997 to 2017 were searched systematically from three databases. Non-adult studies, case reports, reviews and secondary studies were excluded. These studies' characteristics and RV indices reported were summarized. RESULTS: Out of 495 non-duplicated publications found, 81 studies were included in our systematic review. There has been an increasing trend of studying RV function by echocardiography since 2001, and most were conducted in ICU. Thirty-one studies use a single index, mostly TAPSE, to define RV dysfunction; 33 used composite indices and the combinations varied between studies. Seventeen studies did not define RV dysfunction. For those using composite indices, many did not explain their choices. CONCLUSIONS: TAPSE seemed to be the most popular index in the last 2-3 years. Many studies used combinations of indices but, apart from cor pulmonale, we could not find a consistent pattern of RV assessment and definition of RV dysfunction amongst these studies. PMID- 29789864 TI - [Vascularized tumor of the retroauricular skin]. AB - An 84-year-old female patient with loss of hearing and otorrhoea went to an otolaryngologist. On examination, a polypoid mass in the auditory canal and a retroauricular skin lesion, possibly seborrheic keratosis, were found. Only the skin was submitted for histological examination and showed a cutaneous highly vascular lesion with an associated "zellballen" of clear cells without atypia. The initial diagnosis was that of a cutaneous glomangioma. Immunohistochemical findings favored diagnosis of a paraganglioma. Additional clinical information revealed a large mastoid tumor mass. Therefore, the findings were compatible with an jugulotympanic paraganglioma with infiltration of the overlying skin. This possibility was initially not considered in differential diagnosis, as cutaneous glomangiomas are relatively common (typically located on the hands). Cutaneous paragangliomas, however, are not reported. PMID- 29789862 TI - Activating and inhibitory receptors expressed on innate lymphoid cells. AB - Innate lymphoid cells (ILCs) are innate immune cells located in lymphoid and non lymphoid tissues. They are particularly abundant at mucosal and barrier surfaces. Three major ILC subsets are present in humans and mice: group 1 ILCs (comprising natural killer (NK) cells and ILC1s), ILC2s, and ILC3s. ILCs are involved in the maintenance of homeostasis and the regulation of immunity. This review focuses on the extensive array of activating and inhibitory receptors expressed by ILCs for communication with other cell types and their environment in health and disease. PMID- 29789865 TI - The roles of early surgery and comorbid conditions on outcomes of severe necrotizing soft-tissue infections. AB - PURPOSE: Severe necrotizing soft-tissue infections (NSTIs) require immediate early surgical treatment to avoid adverse outcomes. This study aims to determine the impact of early surgery and comorbid conditions on the outcomes of NSTIs. METHODS: A retrospective cohort study was performed on all subjects presenting with NSTI at an academic medical center between 2005 and 2016. Patients were identified based on ICD codes. Those under the age of 18 or with intraoperative findings not consistent with NSTI diagnosis were excluded. RESULTS: There were 115 patients with a confirmed diagnosis of NSTI with a mean age of 55 +/- 18 years; 41% were females and 55% were diabetics. Thirty percent of patients underwent early surgery (< 6 h). There were no significant differences between groups in baseline characteristics. The late group (>= 6 h) had prolonged hospital stay (38 vs. 23 days, p < 0.008) in comparison to the early group (< 6 h). With every 1 h delay in time to surgery, there is a 0.268 day increase in length of stay, adjusted for these other variables: alcohol abuse, number of debridements, peripheral vascular disease, previous infection and clinical necrosis. Mortality was 16.5%. Multivariable analysis revealed that alcohol abuse, peripheral vascular disease, diabetes, obesity, hypothyroidism, and presence of COPD were associated with an increase in mortality. CONCLUSIONS: Early surgical intervention in patients with severe necrotizing soft-tissue infections reduces length of hospital stay. Presence of comorbid conditions such as alcohol abuse, peripheral vascular disease, diabetes, obesity and hypothyroidism were associated with increased mortality. PMID- 29789863 TI - Intricate relationships between naked viruses and extracellular vesicles in the crosstalk between pathogen and host. AB - It is a long-standing paradigm in the field of virology that naked viruses cause lysis of infected cells to release progeny virus. However, recent data indicate that naked virus types of the Picornaviridae and Hepeviridae families can also leave cells via an alternative route involving enclosure in fully host-derived lipid bilayers. The resulting particles resemble extracellular vesicles (EV), which are 50 nm-1 MUm vesicles released by all cells. These EV contain lipids, proteins, and RNA, and generally serve as vehicles for intercellular communication in various (patho)physiological processes. EV can act as carriers of naked viruses and as invisibility cloaks to evade immune attacks. However, the exact combination of virions and host-derived molecules determines how these virus-containing EV affect spread of infection and/or triggering of antiviral immune responses. An underexposed aspect in this research area is that infected cells likely release multiple types of virus-induced and constitutively released EV with unique molecular composition and function. In this review, we identify virus-, cell-, and environment-specific factors that shape the EV population released by naked virus-infected cells. In addition, current findings on the formation and molecular composition of EV induced by different virus types will be compared and placed in the context of the widely proven heterogeneity of EV populations and biases caused by different EV isolation methodologies. Close interactions between the fields of EV biology and virology will help to further delineate the intricate relationship between EV and naked viruses and its relevance for viral life cycles and outcomes of viral infections. PMID- 29789868 TI - Three-Dimensional Imaging in Rhinoplasty: A Comparison of the Simulated versus Actual Result. AB - PURPOSE: Computer imaging has become increasingly popular for rhinoplasty. Three dimensional (3D) analysis permits a more comprehensive view from multiple vantage points. However, the predictability and concordance between the simulated and actual result have not been morphometrically studied. The purpose of this study was to aesthetically and quantitatively compare the simulated to actual rhinoplasty result. METHODS: A retrospective review of 3D images (VECTRA, Canfield) for rhinoplasty patients was performed. Images (preop, simulated, and actual) were randomized. A blinded panel of physicians rated the images (1 = poor, 5 = excellent). The image series considered "best" was also recorded. A quantitative assessment of nasolabial angle and tip projection was compared. Paired and two-sample t tests were performed for statistical analysis (P < 0.05 as significant). RESULTS: Forty patients were included. 67.5% of preoperative images were rated as poor (mean = 1.7). The simulation received a mean score of 2.9 (good in 60% of cases). 82.5% of actual cases were rated good to excellent (mean 3.4) (P < 0.001). Overall, the panel significantly preferred the actual postoperative result in 77.5% of cases compared to the simulation in 22.5% of cases (P < 0.001). The actual nasal tip was more projected compared to the simulations for both males and females. There was no significant difference in nasal tip rotation between simulated and postoperative groups. CONCLUSION: 3D simulation is a powerful communication and planning tool in rhinoplasty. In this study, the actual result was deemed more aesthetic than the simulated image. Surgeon experience is important to translate the plan and achieve favorable postoperative results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 29789869 TI - The race for drug approvals: hasten slowly? PMID- 29789870 TI - Acute kidney injury, agranulocytosis, drug-induced liver injury, and posterior reversible encephalopathy syndrome caused by high-dose methotrexate-possible role of low activity ABC and SLC drug transporters. PMID- 29789867 TI - MAP kinase signalling: interplays between plant PAMP- and effector-triggered immunity. AB - In plants, mitogen-activated protein kinase (MAPK) cascades are involved in regulating many biological processes including immunity. They relay signals from membrane-residing immune receptors to downstream components for defense activation. Arabidopsis MPK3/6 and MPK4 are activated in two parallel MAPK cascades during PAMP-triggered immunity. MPK3/6 have been implicated in the activation of various immune responses and their inactivation leads to compromised defense against pathogens. On the other hand, the MEKK1-MKK1/2-MPK4 cascade plays critical roles in basal resistance. Disruption of this MAPK cascade results in constitutive defense responses mediated by the NB-LRR protein SUMM2. Interestingly, SUMM2 guards the MEKK1-MKK1/2-MPK4 cascade activity indirectly through monitoring the phosphorylation status of CRCK3, which is a substrate of MPK4. From the pathogens' side, a number of effectors are shown to target various components of MAPK cascades in plants. Inactivation of MPK4 by the Pseudomonas effector HopAI1 triggers SUMM2-mediated immunity. Together, these findings suggest intricate interplays between PAMP-triggered immunity and effector triggered immunity via MAPK signaling. PMID- 29789871 TI - Emergency admissions for complicated colonic diverticulitis are increasing: a nationwide register-based cohort study. AB - BACKGROUND: Acute colonic diverticulitis is common in the Western world representing a growing burden on health care. We aimed to report the factual epidemiological and demographic characteristics in patients with acute diverticulitis in a large nationwide population. METHOD: We conducted a population-based cohort study from 2000 to 2012 on the complete Danish population, which included all patients with acute colonic diverticulitis. Data were composed through two national longitudinal registries. The study main outcomes were demographic development regarding hospital admission, age, gender, geographical residency, and seasonal information. RESULTS: A total of 101,963 acute hospital contacts were identified from 2000 to 2012, of these 44,160 were due to acute diverticulitis. From 2000 to 2012, overall admission rates for complicated diverticulitis increased significantly with 42.7%. There was a small increase in hospital admissions due to acute diverticulitis, and uncomplicated diverticulitis accounted for 83-88% of all admissions. No significant development was seen in cases of uncomplicated diverticulitis. The majority of patients were older than 50 years (85%) and 60% were women. The male gender dominated in patients younger than 50 years (58%), whereas women dominated above 50 years (63%). Mean age and dominating age group decreased significantly from 2000 to 2012 for both genders. A significantly larger proportion of male patients had complicated diverticulitis than uncomplicated diverticulitis. Most admissions were seen during autumn. CONCLUSION: We found that acute colonic diverticulitis has been progressing over the last decade with more severe cases of disease. Our findings underline the need for further research to identify the relevant risk factors and causal circumstances. PMID- 29789866 TI - Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation. AB - Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide. Inflammation plays an important role in the development of numerous liver diseases, contributing to the progression to more severe stages, such as non-alcoholic steatohepatitis and hepatocellular carcinoma. Peroxisome proliferator-activated receptors (PPARs) are binder-activated nuclear receptors that are involved in the transcriptional regulation of lipid metabolism, energy balance, inflammation and atherosclerosis. Three isotypes are known: PPAR-alpha, PPARdelta/beta and PPAR-gamma. These isotypes play different roles in diverse tissues and cells, including the inflammatory process. In this review, we discuss current knowledge on the role PPARs in the hepatic inflammatory process involved in NAFLD as well as new pharmacological strategies that target PPARs. PMID- 29789872 TI - Endovascular Thrombectomy for Large-Vessel Occlusion Strokes with Preexisting Intracranial Aneurysms. AB - OBJECTIVE: This study aimed to investigate the safety of endovascular thrombectomy in acute ischemic stroke with preexisting intracranial aneurysms. METHODS: Patients with acute ischemic stroke due to large-artery occlusion combined with intracranial aneurysms, who received endovascular treatment, were analyzed retrospectively, and the procedure-related data were recorded. RESULTS: Among the 124 patients who suffered acute large-artery occlusion and received endovascular recanalization therapy, intracranial aneurysms were found in seven patients (5.6%). All the seven patients achieved successful recanalization, except one patient who suffered subarachnoid hemorrhage due to the rupture of aneurysm during the procedure. CONCLUSIONS: The prevalence of preexisting cerebral aneurysms in patients with acute ischemic stroke is high, leading to a procedure-related rupture risk. Endovascular treatment devices must be used carefully in these patients, especially when the aneurysms are located within the area where the procedure is performed. PMID- 29789873 TI - New Implant-Based Technologies in the Spine. AB - Vertebral compression fractures (VCFs) may result in a kyphotic deformity which can cause potential systemic complications secondary to respiratory and gastrointestinal dysfunction. The use of implants in the spine for VCF treatment represents a paradigm shift away from cement injection on its own, aiming to combine the analgesic and stabilizing effect of injecting cement into the vertebral body with vertebral height restoration and kyphotic angle correction. Spine implants which can be used for VCF treatment include stents, jacks, PEEK cages and fracture reduction systems. Lumbar spinal stenosis (LSS) with neurogenic intermittent claudication is one of the most commonly occurring spinal conditions, usually affecting people older than 50, which can cause disability and a reducted quality of life. Percutaneous interspinous spacers for the relief of symptoms caused by spinal stenosis can be used in patients who are not surgical candidates. The purpose of this article is to describe the basic concepts of spinal implantation in patients with VCF or spinal stenosis. The role of biomechanics and the different types of implants will be described. Controversies concerning techniques and products will be addressed. Finally, the necessity for an individually tailored approach for the use of different implants in different cases and anatomic locations will be emphasized. PMID- 29789874 TI - The Interventional Radiology (IR) Gender Gap: A Prospective Online Survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). AB - AIM: A prospective online survey was conducted by the Cardiovascular Interventional Radiological Society of Europe (CIRSE) to evaluate the gender gap within interventional radiology (IR) and the barriers facing women in IR. MATERIALS AND METHODS: A questionnaire ("Appendix") was devised by the authors and the CIRSE communication and publication team and sent electronically to 750 identifiable female members of CIRSE. Responses were collected from 7 August to 24 August 2017. RESULTS: The response rate was 19.9% (n = 149) with highest responses from UK (18%), Italy (11%), Germany (11%), Spain (7%), Netherlands (5%), France (5%), Sweden (4%), USA (4%). 91% of the respondents were between 31 and 46 years, 83% work full time, 62% spend > 50% of their working time in IR, and 67% practice in a university or tertiary referral institution. 85% were in the minority in their department. 52% had no leadership role in their department, but 67% expressed willingness to consider a leadership position. Their main concerns were work/family life balance, the risks of radiation exposure, the effect of pregnancy on training and practice and the male-dominated work environment. CONCLUSION: This survey highlights issues experienced by women in IR. Clear guidance on concerns regarding radiation exposure particularly during pregnancy is needed. Structured and supportive training is required for female IRs who may wish to train or work flexibly. The male-dominated environment is discouraging, and a scheme to promote female IRs would encourage women to take on senior leadership positions and attract more women into the specialty. PMID- 29789876 TI - [New treatment option-apalutamide for nonmetastatic, castration-resistant prostate cancer]. PMID- 29789877 TI - [Meta-analyses on measurement precision of non-invasive hemodynamic monitoring technologies in adults]. AB - An ideal non-invasive monitoring system should provide accurate and reproducible measurements of clinically relevant variables that enables clinicians to guide therapy accordingly. The monitor should be rapid, easy to use, readily available at the bedside, operator-independent, cost-effective and should have a minimal risk and side effect profile for patients. An example is the introduction of pulse oximetry, which has become established for non-invasive monitoring of oxygenation worldwide. A corresponding non-invasive monitoring of hemodynamics and perfusion could optimize the anesthesiological treatment to the needs in individual cases. In recent years several non-invasive technologies to monitor hemodynamics in the perioperative setting have been introduced: suprasternal Doppler ultrasound, modified windkessel function, pulse wave transit time, radial artery tonometry, thoracic bioimpedance, endotracheal bioimpedance, bioreactance, and partial CO2 rebreathing have been tested for monitoring cardiac output or stroke volume. The photoelectric finger blood volume clamp technique and respiratory variation of the plethysmography curve have been assessed for monitoring fluid responsiveness. In this manuscript meta-analyses of non-invasive monitoring technologies were performed when non-invasive monitoring technology and reference technology were comparable. The primary evaluation criterion for all studies screened was a Bland-Altman analysis. Experimental and pediatric studies were excluded, as were all studies without a non-invasive monitoring technique or studies without evaluation of cardiac output/stroke volume or fluid responsiveness. Most studies found an acceptable bias with wide limits of agreement. Thus, most non-invasive hemodynamic monitoring technologies cannot be considered to be equivalent to the respective reference method. Studies testing the impact of non-invasive hemodynamic monitoring technologies as a trend evaluation on outcome, as well as studies evaluating alternatives to the finger for capturing the raw signals for hemodynamic assessment, and, finally, studies evaluating technologies based on a flow time measurement are current topics of clinical research. PMID- 29789875 TI - CT Angiography in the Lower Extremity Peripheral Artery Disease Feasibility of an Ultra-Low Volume Contrast Media Protocol. AB - PURPOSE: The ALARA principle is not only relevant for effective dose (ED) reduction, but also applicable for contrast media (CM) management. Therefore, the aim was to evaluate the feasibility of an ultra-low CM protocol in the assessment of peripheral artery disease (PAD). MATERIALS AND METHODS: Fifty PAD patients were scanned on third-generation dual-source computed tomography, from diaphragm to the forefoot, as follows: tube voltage: 70 kV, reference effective tube current: 90 mAs, collimation: 192 * 2 * 0.6 mm, with individualized acquisition timing. The protocol ED (mSv) was quantified with dedicated software. CM protocol consisted of 15 ml test bolus and 30 ml main bolus (300 mgI/ml) injected at 5 ml/s, followed by a 40 ml saline chaser at the same flow rate. Aorto-popliteal bolus transit time was used to calculate the overall acquisition time and delay. Objective (hounsfield units-HU; contrast-to-noise ratio-CNR) and subjective image quality (four-point Likert score) were assessed at different anatomical regions from the aorta down to the forefoot. RESULTS: Mean attenuation values were exceeding 250 HU from aorta down to the anterior tibial artery with CNR < 13. However, decline in attenuation was observed in more distal region with mean values of 165 and 199 HU, in left and right dorsalis pedis artery, respectively. Mode subjective image quality from the level of aorta down to the popliteal segment was excellent; below the knee mode score was good. The mean ED per protocol was 1.1 +/- 0.5 mSv. CONCLUSION: Use of an ultra-low CM volume protocol at 70 kV is feasible in the evaluation of PAD, resulting in good to excellent image quality with mean ED of 1.1 +/- 0.5 mSv. LEVEL OF EVIDENCE: Level 3, Local non-random sample. PMID- 29789879 TI - Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation. AB - AIMS/HYPOTHESIS: The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment. METHODS: Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice. RESULTS: At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean +/- SEM: 0.118 +/- 0.01 [n = 3] in Vegf-A mRNA transfected group (VEGF) vs 0.056 +/- 0.01 [n = 3] in no RNA [p < 0.05] vs 0.063 +/- 0.02 [n = 4] in Gfp mRNA transfected group (GFP) [p < 0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085 +/- 0.02 [n = 4] in VEGF vs 0.030 +/- 0.004 [n = 4] in no RNA [p < 0.05] vs 0.034 +/- 0.01 [n = 5] in GFP [p < 0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048 +/- 0.013 [n = 3] in VEGF vs 0.015 +/- 0.0051 [n = 4] in no RNA [p < 0.01] vs 0.013 +/- 0.0046 [n = 4] in GFP [p < 0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049 +/- 0.0042 [n = 8] in VEGF vs 0.029 +/- 0.0052 [n = 5] in no RNA [p < 0.05] vs 0.027 +/- 0.0056 [n = 4] in GFP [p < 0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292 +/- 0.0032 MUl [n = 7] in VEGF vs 0.0178 +/- 0.0021 MUl [n = 5] in no RNA [p < 0.01] vs 0.0129 +/- 0.0012 MUl [n = 4] in GFP [p < 0.001]). CONCLUSIONS/INTERPRETATION: Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants. PMID- 29789878 TI - Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial. AB - AIMS/HYPOTHESIS: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. METHODS: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. RESULTS: A total of 108 participants had post intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by 2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 angstrom [LDL-c<255A]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255A (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. CONCLUSIONS/INTERPRETATION: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada. PMID- 29789880 TI - Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients. AB - Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naive and memory receptors as well as beta2m-associated and beta2m-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age matched controls (CTR). We show that the peripheral CD3+CD8+ T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3+CD8high T cell population enriched in effector-memory CD45RA+ T cells (CD8+ TEMRA) when compared to CTR (P < 0.001), and a less granular CD3+CD8int T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naive (CD8+ TN) and CD8+ TEMRA cells expressing intermediate levels of CD28, i.e., CD3+CD8intCD28int. While the percentage of CD3+CD8int TN cells correlated positively with the number of erythrocytes, the percentage of CD3+CD8int TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32+) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10+) MHC-I conformers. The implications of this distinctive immune signature are discussed. PMID- 29789881 TI - Characterization of recombinant E. coli expressing arsR from Rhodopseudomonas palustris CGA009 that displays highly selective arsenic adsorption. AB - Innovative methods to lower arsenic (As) exposure are sought. The As regulatory protein (ArsR) is reported of having high affinity and specificity to arsenite [As(III)]. Rhodopseudomonas palustris CGA009 is a good model organism for studying As detoxification due to at least three ars operons and four diverse arsRRP1-4 on the genome. In this study, four Escherichia coli harboring arsRRP1-4 derived from CGA009 were engineered and tested regarding their As resistance. The results showed that E. coli (arsRRP2) displayed robust As(III) resistance, and its growth inhibition rate was only 2.9% when exposed to 3.0 mmol/L As(III). At pH 7.0, E. coli (arsRRP2) showed an enhanced As adsorption capacity. As(III) (2.32 mg/g (dry weight, dw)) and 1.47 mg/g arsenate [As(V)] was adsorbed representing a 4.2-fold and 1.3-fold increase respectively compared to the control strain. The adsorption process was well fitted to Langmuir isothermal mode. E. coli (arsRRP2) (1.0~12.0 g/L) could remove 30.3~82.2% of As (III) when exposed to 10 MUg/L As(III). No increase in absorption to copper(II), zinc(II), chromium(III), and lead(II) could be detected. Our studies revealed that arsRRP1 4 from CGA009 could confer As(III) resistance; E. coli (arsRRP2) displayed the highest As resistance, selectivity, and adsorption capacity within a wider pH (5.0~9.0) and salinity (0~15.0 g/L NaCl) range, especially important as it could remove As(III) from low concentration As-containing water. PMID- 29789882 TI - Rapid development of stable transgene CHO cell lines by CRISPR/Cas9-mediated site specific integration into C12orf35. AB - Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production. However, by conventional random integration strategy, development of a high-expressing and stable recombinant CHO cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. Site-specific integration of transgenes into CHO hot spots is an ideal strategy to overcome these challenges since it can generate isogenic cell lines with consistent productivity and stability. In this study, we investigated three sites with potential high transcriptional activities: C12orf35, HPRT, and GRIK1, to determine the possible transcriptional hot spots in CHO cells, and further construct a reliable site specific integration strategy to develop recombinant cell lines efficiently. Genes encoding representative proteins mCherry and anti-PD1 monoclonal antibody were targeted into these three loci respectively through CRISPR/Cas9 technology. Stable cell lines were generated successfully after a single round of selection. In comparison with a random integration control, all the targeted integration cell lines showed higher productivity, among which C12orf35 locus was the most advantageous in both productivity and cell line stability. Binding affinity and N glycan analysis of the antibody revealed that all batches of product were of similar quality independent on integrated sites. Deep sequencing demonstrated that there was low level of off-target mutations caused by CRISPR/Cas9, but none of them contributed to the development process of transgene cell lines. Our results demonstrated the feasibility of C12orf35 as the target site for exogenous gene integration, and strongly suggested that C12orf35 targeted integration mediated by CRISPR/Cas9 is a reliable strategy for the rapid development of recombinant CHO cell lines. PMID- 29789883 TI - Functional characterization of a thermostable endoglucanase belonging to glycoside hydrolase family 45 from Fomitopsis palustris. AB - A gene encoding an endoglucanase belonging to subfamily C of glycoside hydrolase family 45 (GH45) was identified in the brown rot fungus Fomitopsis palustris and functionally expressed in Pichia pastoris. The recombinant protein displayed hydrolytic activities toward various substrates such as carboxymethyl cellulose, phosphoric acid swollen cellulose, glucomannan, lichenan, and beta-glucan. In particular, the enzyme had a unique catalytic efficiency on beta-1,4-glucans rather than mixed beta-1,3/1,4-glucans as compared to other GH45 endoglucanases. The fungal enzyme was relatively thermostable, retaining more than 91.4% activity at 80 degrees C for 1 h. Site-directed mutagenesis studies revealed that the mutants N95D and D117N had significantly reduced enzymatic activities, indicating that both residues are essential for the catalytic reaction. Our study expands knowledge and understanding of the catalytic mechanism of GH45 subfamily C enzymes and also suggests that this thermostable endoglucanase from F. palustris has great potential in industrial applications. PMID- 29789884 TI - Biosphere Reserve for All: Potentials for Involving Underrepresented Age Groups in the Development of a Biosphere Reserve through Intergenerational Practice. AB - Stakeholder participation is of high importance in UNESCO biosphere reserves as model regions for sustainable development; however, certain groups remain underrepresented. The paper proposes Intergenerational Practice (IP) as a means of involving youth and elderly women and explores its options and barriers, using the example of the Salzburger Lungau and Karntner Nockberge Biosphere Reserve in Austria. Case study analysis is used involving mixed methods. The results reveal obstacles and motivations to participating in biosphere reserve implementation and intergenerational activities for the youth and the elderly women and imply that much potential for IP exists in the biosphere reserve region. The authors propose suitable solutions from the intergenerational field to overcome identified participation obstacles and suggest benefits of incorporating IP as a management tool into biosphere reserve activities. Suggestions for future research include evaluating applications of IP in the context of protected areas, testing of methods used in other contexts, and contribution to theory development. PMID- 29789885 TI - Instability of endosperm development in amphiploids and their parental species in the genus Avena L. AB - KEY MESSAGE: The development of oat endosperm is modified by chromatin and nuclei elimination, intrusive growth of cell walls, and polyploidisation of cell clones. The last event is correlated with somatic crossing-over. Grass endosperm is a variable tissue in terms of its cytogenetics and development. Free-nuclear syncytium and starchy and aleurone endosperm were the main focus of the research. These were studied in oat amphiploids (4x, 6x, and 8x) and parental species (2x, 4x, and 6x). What the levels of cytogenetic disorders and developmental anomalies in species versus hybrids are, and, what the factors are determining phenotypes of both tissue components, are open questions for oats. Chromosome bridges and micronuclei are the main cytogenetic disorders showing the elimination of parts of genomes. Bridges are formed by the AT-heterochromatin-rich and -free ends of chromosomes. In the starchy tissue, various sectors are separated structurally due to the elongation or intrusive growth of aleurone cells. The development of the aleurone layer is highly disturbed locally due to the amplification of aleurone cell divisions. Changes related to their structure and metabolism occur in the aleurone cells, for example, clones of small versus large aleurone cells. Somatic crossing-over (SCO) is expressed in clones of large polyploidised cells (r = 0.80***), giving rise to new aleurone phenotypes. The multivariate description of the endosperm instability showed that endospermal disorders were more frequent in amphiploids than in the oat species. Avena strigosa and the amphiploid A. fatua * A. sterilis appeared to be extreme units in an ordination space. Nuclear DNA elimination, periclinal and multidirectional cytokineses, polyploidisation, intrusive growth, and SCO appeared to be important factors determining oat endospermal variations. PMID- 29789887 TI - Proven accuracy for a new dynamic gap measurement in navigated TKA. AB - PURPOSE: Clinical outcome of TKA remains unsatisfactory in 20% of the cases. Navigation has added accuracy in terms of alignment, but has improved clinical outcome only in small series with gap-balanced techniques. Reason for that could be that conventional gap balanced TKA determines gaps in extension and 90 degrees of flexion only. Furthermore, measurement is only static. Therefore, the accuracy of a new dynamic navigation software which allows gap assessment throughout the entire range of motion was tested. The purpose of this study was to investigate the accuracy and reliability of dynamic gap testing during gap balanced TKA. METHODS: In two different centres, a total of 65 TKA procedures were performed in a tibia-first, gap-balanced technique using a new CAS software. At the same and at different time points of surgery, two different surgeons performed gap measurement to provide inter-observer reliability data and repeated gap measurement to provide intra-observer reliability data. These gap measurements were performed throughout the entire ROM under dynamic stress testing to detect maximum gap values. RESULTS: CAS surgery was able to produce correct coronal alignment in 96.4% of the cases (within 3 degrees mechanical alignment). Both inter-observer and intra-observer reliabilities were excellent for gap values throughout the entire ROM. Inter-observer bias of deviation 0.05; 95% limits of agreement of - 2.1 to + 2.21 mm. Intra-observer bias of deviation 0.09; 95% limits of agreement of - 2.27 to + 2.44 mm. CONCLUSIONS: This new CAS software in combination with the presented dynamic gap measurement provides accurate gap values and therefore facilitates balancing TKA. This technique works reproducibly for different surgeons and has proven robustness also for repeated measurements of any surgeon in this study. PMID- 29789888 TI - Diffusion tensor imaging in acute pyelonephritis in children. AB - BACKGROUND: Diffusion-weighted imaging plays a key role in the imaging of acute pyelonephritis by MRI. However the use of respiratory triggering is challenging and time-consuming in children. Diffusion tensor imaging without respiratory triggering might provide satisfying images of the moving kidneys. OBJECTIVE: To compare mean diffusivity diffusion tensor images obtained with free breathing with diffusion-weighted images obtained with respiratory triggering. MATERIALS AND METHODS: Thirty-one children with suspected acute pyelonephritis underwent axial diffusion tensor imaging acquisition with free breathing and axial and coronal diffusion-weighted imaging acquisitions with respiratory triggering. We compared image quality and detection of nephritis between the two sequences. RESULTS: Diffusion tensor imaging demonstrated agreement with diffusion-weighted imaging in all cases, with no difference in the detection of nephritis areas. The image quality was significantly better with diffusion tensor imaging (P<0.01). CONCLUSION: Diffusion tensor imaging could replace diffusion-weighted imaging for diagnosis of acute pyelonephritis. PMID- 29789886 TI - GCTTCA as a novel motif for regulating mesocarp-specific expression of the oil palm (Elaeis guineensis Jacq.) stearoyl-ACP desaturase gene. AB - KEY MESSAGE: TAAAAT and a novel motif, GCTTCA found in the oil palm stearoyl-ACP desaturase (SAD1) promoter are involved in regulating mesocarp-specific expression. Two key fatty acid biosynthetic genes, stearoyl-ACP desaturase (SAD1), and acyl-carrier protein (ACP3) in Elaeis guineensis (oil palm) showed high level of expression during the period of oil synthesis in the mesocarp [12 19 weeks after anthesis (w.a.a.)] and kernel (12-15 w.a.a.). Both genes are expressed in spear leaves at much lower levels and the expression increased by 1.5-fold to 2.5-fold following treatments with ethylene and abscisic acid (ABA). Both SAD1 and ACP3 promoters contain phytohormone-responsive, light-responsive, abiotic factors/wounding-responsive, endosperm specificity and fruit maturation/ripening regulatory motifs. The activities of the full length and six 5' deletion fragments of the SAD1 promoter were analyzed in transiently transformed oil palm tissues by quantitative beta-glucuronidase (GUS) fluorometric assay. The highest SAD1 promoter activity was observed in the mesocarp followed by kernel and the least in the leaves. GUS activity in the D3 deletion construct (- 486 to + 108) was the highest, while the D2 (- 535 to + 108) gave the lowest suggesting the presence of negative cis-acting regulatory element(s) in the deleted - 535 to - 486 (49 bp). It was found that the 49-bp region binds to the nuclear protein extract from mesocarp but not from leaves in electrophoretic mobility shift assay (EMSA). Further fine-tuned analysis of this 49-bp region using truncated DNA led to the identification of GCTTCA as a novel motif in the SAD1 promoter. Interestingly, another known fruit ripening-related motif, LECPLEACS2 (TAAAAT) was found to be required for effective binding of the novel motif to the mesocarp nuclear protein extract. PMID- 29789889 TI - Developing a reference MRI database for temporomandibular joints in healthy children and adolescents. AB - BACKGROUND: Recognition of normal temporomandibular joints (TMJs) is essential to assess arthropathic changes. Few, if any, prior studies have evaluated the morphological appearance of growing TMJs by magnetic resonance (MR) examinations in the pediatric population. OBJECTIVE: This study aimed to determine normative osseous appearance of growing TMJs according to age and gender, both qualitatively and quantitatively, concerning structural and bone marrow changes. MATERIALS AND METHODS: From 1,036 MR scans screened, one joint was included from each of 157 patients (76% female; 2-18 years) presenting with at least one normal appearing TMJ was included. Quantitatively, mandibular condyle was characterized by measuring the following: (i) head-neck angle, (ii) anteversion angle, (iii) condylar dimensions (mediolateral, craniocaudal and anteroposterior [AP]) and (iv) condylar volume. Furthermore, qualitative categorization of condylar shape, into one of three types, and condylar bone marrow type was performed. RESULTS: The head-neck angle significantly correlated with age (bivariable regression beta =0.60, P<0.001), indicating an increase of 1.6 degrees per year. Except for AP diameter of condyles, all other mandibular dimensions and condylar volume increased with age (beta =0.20-0.59, P<=0.001-0.004). Significant age difference was observed among the different condylar shapes (P<0.001), indicating a change from rounded head without anterior tilt to rectangular head with anterior tilt. Lastly, mandibular condylar size, measured by volume and by AP and mediolateral dimensions, appeared larger in males. CONCLUSION: The morphology of the mandibular condyles changes with age. During development, the shape of the condyles changes from round to rectangular in contour with the development of the anterior condylar tilt, as measured by the head-neck angle. PMID- 29789891 TI - [Overview of indicators in the context of environment and health]. AB - BACKGROUND: Evidence-based political measures need reliable information about the health status of a population and the determinants affecting health. Here, environment and health indicators can provide helpful additional insights. AIM: This article provides an overview of existing indicators in the field of environment and health. MATERIALS: There are single indicators and indicator sets describing solely the environment or health as well as some indicators integrating both aspects. RESULTS: The indicator sets cover classical epidemiological indicators but also summary measures of population health, which combine mortality and morbidity as well as simple descriptions of the exposure towards environmental risks. The indicator sets mostly cover water and air quality related aspects. For some of the indicators their influence on health is also presented. Furthermore, environment related health indicators are part of sustainability indicator sets. There are indicators on the international, European, national, and municipal level. DISCUSSION: All indicator sets aim to support policy-making by advising on measures and setting priorities in the area of environment and health protection. However not all indicators reflect the effect of the environment on health adequately. Therefore, further development of the existing indicators is necessary to reflect current progress (e. g. political needs) and to include new scientific evidence in the field of environment and health. A continuous provision, review, and interpretation of meaningful indicators is required to identify trends and to react to these in order to protect the environment and health. This is necessary to adequately pursue the precautionary principle. PMID- 29789892 TI - [The significance of climate and environment protection for health under special consideration of skin barrier damages and allergic sequelae]. AB - The skin, together with gut and respiratory tract, harbor a central epithelial barrier function in regards to the interaction of an individual with the environment. Continuing exposure to environmental influences can cause epithelial barrier damages and thus pave the way for atopy development. The latter describes the tendency for allergies, i. e. hypersensitivity of the skin, intestine, and respiratory tract towards per se unharmful environmental substances.Allergies are classified as non-communicable diseases (NCDs). According to the World Health Organization (WHO), they are presently the most demanding medical challenge. Allergies are the most frequent NCDs and are characterized by a high and multi facetted level of suffering. An enormous socio-economic burden and the urgent need for effective prevention follows as consequence. Prevention options have by no means been sufficiently used. Within the skin barrier's key function in regards to the defense of atopic diseases are so far inadequately used prevention possibilities. They are based on ambitious environmental and climatic policy that pointedly addresses the barrier disrupting environmental factors.On the basis of this proposition, the present article assigns appropriate environmental and climatic policy measures. The two main arguments for such measures are a disburdening of the healthcare system as well as a far better life quality for the affected people. They are the legitimization towards an ambitious environmental and climatic policy. For its realization an integrated approach of (allergy) prevention and environmental research is necessary. Now, campaigning for its acceptance in politics and society is an urgent matter. PMID- 29789890 TI - Surveillance magnetic resonance imaging for isolated optic pathway gliomas: is gadolinium necessary? AB - BACKGROUND: Pediatric optic pathway gliomas are typically indolent but have a variable clinical course. Treatment is dictated by symptoms and changes on contrast-enhanced MRI examinations. Gadolinium retention in children has motivated parsimonious use of gadolinium-based contrast agents. OBJECTIVES: To determine surveillance MR factors that motivate changes in tumor-directed therapies and extrapolate cost-efficacy of a non-contrast follow-up protocol. MATERIALS AND METHODS: Using an imaging database search we identified children with isolated optic pathway gliomas and >=3 follow-up contrast-enhanced MRIs. We reviewed medical records and imaging for: (1) coincident changes on contrast enhanced MRI and tumor-directed therapy, (2) demographics and duration of follow up, (3) motivations for intervention, (4) assessment of gadolinium-based contrast agents' utility and (5) health care utilization data. We assessed cost impact in terms of relative value unit (RVU) burden. RESULTS: We included 17 neurofibromatosis type 1 (NF1) and 21 non-NF1 patients who underwent a median 16.9 and 24.3 cumulative contrast-enhanced MR exams over 7.7 years and 8.1 years of follow-up, respectively. Eight children (one with NF1) had intervention based on contrast-enhanced MR findings alone. For these eight, increased tumor size was the only common feature, and it was apparent on non-contrast T2 sequences. For the median patient, a non-contrast follow-up protocol could result in 15.9 (NF1) and 23.3 (non-NF1) fewer gadolinium-based contrast agent administrations, and a 39% lower yearly RVU burden. CONCLUSION: Pediatric patients with isolated optic pathway gliomas undergo a large number of routine contrast-enhanced MR follow-up exams. Gadolinium might not be needed for these exams to inform management decisions. Secondary benefits of a non-contrast follow-up protocol include decreased cost and risk to the patient. PMID- 29789893 TI - [Integration of sex/gender into environmental health research. Results of the interdisciplinary research network Sex/Gender-Environment-Health (GeUmGe-NET)]. AB - The comprehensive consideration of sex/gender in health research is essential to increase relevance and validity of research results. Contrary to other areas of health research, there is no systematic summary of the current state of research on the significance of sex/gender in environmental health. Within the interdisciplinary research network Sex/Gender-Environment-Health (GeUmGe-NET) the current state of integration of sex/gender aspects or, respectively, gender theoretical concepts into research was systematically assessed within selected topics of the research areas environmental toxicology, environmental medicine, environmental epidemiology and public health research on environment and health. Knowledge gaps and research needs were identified in all research areas. Furthermore, the potential for methodological advancements by using gender theoretical concepts was depicted. A dialogue between biomedical research, public health research, and gender studies was started with the research network GeUmGe NET. This dialogue has to be continued particularly regarding a common testing of methodological innovations in data collection and data analysis. Insights of this interdisciplinary research are relevant for practice areas such as environmental health protection, health promotion, environmental justice, and environmental health monitoring. PMID- 29789894 TI - [Conditio sine qua non: environment and health]. PMID- 29789897 TI - [Pilot study to investigate sleep disorders in the blind and persons with relevant visual impairment]. AB - BACKGROUND: Sleep disorders are associated with serious health problems in blind and visually impaired persons. Loss of light perception may result in a shift of sleep-wake pattern, which may lead to significant impairments in daily life--the so-called non-24-hour sleep-wake disorder. To date, epidemiologic data on non-24 only exist for the USA. This pilot study was conducted to provide first epidemiologic data for the prevalence of non-24 and other sleep disorders among blind and visually impaired persons in Germany. METHODS: Recruited were 111 blind and visually impaired subjects (36 subjects without light perception; male [m] = 56, 27-85 years, average [Mx] = 59.53, standard deviation [SD] = 14.69) and 111 sighted controls (m = 41, 27-88 years, Mx = 58.32, SD = 14.21), who answered a set of validated questionnaires referring to general health status (SF-36), sleep characteristics (PSQI), and daytime sleepiness (ESS). In addition, a questionnaire to predict non-24-hour sleep-wake disorder, which is not yet validated in German, was provided. RESULTS: The prevalence of 72.2% for the non 24-hour sleep-wake disorder in blind people is in accordance with results from the USA. In contrast, our results indicated non-24 in only 21.3% of the subjects with residual light perception. Furthermore, other sleep disorders like problems falling asleep (100% vs. 79.9%), maintaining sleep (90% vs. 88.1%), sleep disordered breathing (19.4% vs. 32%), or sleep-related movement disorders (28.1% vs. 32.9%) were also common in the group of blind or visually impaired persons. DISCUSSION: The non-24-hour sleep-wake disorder is a frequent problem among people with no light perception, associated with problems falling asleep, maintaining sleep, and daytime sleepiness. The perception of light as an external cue for our circadian rhythm plays a key role. However, sleep disruption is not fully explained by non-24, making a detailed sleep history essential. PMID- 29789898 TI - [Clinical parameters of patients with neovascular age-related macular degeneration : Longterm treatment results of an outpatient clinic]. AB - BACKGROUND: The clinical outcome of neovascular age-related macular degeneration (nAMD) depends on constant follow-up and consistent treatment. Data about the long-term course of intensive anti-vascular endothelial growth factor (VEGF) therapy from outpatient clinics are rare. OBJECTIVE: The aim of the study was to characterize a population of nAMD patients with long-term follow-up and intensive anti-VEGF therapy. PATIENTS AND METHODS: In a supra-regional outpatient clinic, we retrospectively identified patients who had received at least 30 intravitreal anti-VEGF injections and were followed for at least 4 years. All patients received an optical coherence tomography(OCT)-controlled Pro-Re-Nata (PRN) therapy regimen according to German guidelines. RESULTS: We identified 43 patients. Visual acuity at baseline was 0.44 +/- 0.24 (1.0-0.1) logMAR. At the end of the follow-up period, visual acuity was 0.63 +/- 3.6 (1.3-0.1) logMAR. Patients received a mean of 36.3 +/- 8.0 (30-62) injections and were followed for a mean of 6.1 +/- 1.8 (4-12) years. They received 6.12 +/- 1.5 (3.1-9.9) injections per year. The number of injections in treatment-year one was with 3.67 +/- 1.9 (1-8) significantly lower than the mean (p < 0.0001). CONCLUSION: Despite intensive PRN therapy, visual acuity slowly decreased over time. The mean number of injections was comparable to that of prospective studies. The low number of injections in treatment-year 1 may have been due to a lack of experience with the new treatment agents. The slow decrease in visual acuity in clinical routine as opposed to clinical studies may be attributed to a delay between occurrence of disease activity and treatment. PMID- 29789899 TI - [Review of clinical trials in retinopathy of prematurity : Current state and future perspectives]. AB - BACKGROUND: The treatment of retinopathy of prematurity (ROP) has gained a new dynamic since the introduction of anti-vascular endothelial growth factor (VEGF) therapy. This review summarizes clinical trial data in order to aid informed decision-making. METHODS: In this article, pivotal clinical trials are summarized and discussed with regard to their implications for ROP therapy. RESULTS: The longest follow-up phase exists for children treated in the CRYO-ROP study, which used retinal cryocoagulation to treat ROP. Based on results of the ETROP study and others, retinal laser therapy has replaced cryotherapy as standard of care. For anti-VEGF treatment, three controlled clinical trials exist to date: BEAT ROP, CARE-ROP, and the PEDIG study. Combined, these studies demonstrate efficacy of anti-VEGF in treating acute ROP. However, they also emphasize the risk of (late) recurrences and the largely unsolved questions regarding choice of drug and dose as well as long-term safety. CONCLUSION: Treatment of ROP remains a highly individual decision in which many variables need to be considered. The data discussed in this article can help in decision-making and emphasize the unique characteristics of the available therapeutic approaches, in particular regarding postoperative follow-up. PMID- 29789895 TI - Diffusion-weighted imaging determinants for acute ischemic stroke diagnosis in the emergency room. AB - PURPOSE: The aim of this study was to investigate the clinical-radiological determinants of diffusion-weighted image (DWI) abnormalities in patients with suspected acute ischemic stroke (AIS) seen at the emergency room (ER). METHODS: During the study period, 882 consecutive patients were screened at Clinica Alemana de Santiago, Chile; 786 had AIS and 711 (90.4%) were included. RESULTS: DWI demonstrated 87.3% sensitivity and 99.0% specificity, with a positive likelihood ratio of 79 and a negative likelihood ratio of 0.13 for the detection of AIS. In the univariate analysis, a positive DWI in AIS was associated with admission National Institute of Health Stroke Scale (NIHSS) score (OR 1.09, 95% CI 1.04-1.1%), time from symptom onset to DWI (OR 1.03, 95% CI 1.01-1.05), presence of a relevant intracranial artery occlusion (OR 3.18, 95% CI 1.75-5.76), posterior circulation ischemia (OR 0.44, 95% CI 0.28-0.7), brainstem location of the AIS (OR 0.16, 95% CI 0.093-0.27), infratentorial location of AIS (OR 0.44, 95% CI 0.28-0.70), and lacunar (OR 0.27, 95% CI 0.11-0.68) or undetermined stroke etiology (OR 0.12, 95% CI 0.3-0.31). In multivariate analysis, only admission NIHSS score (OR 1.07, 95% CI 1.01-1.13), time from symptom onset to DWI (OR 1.04, 95% CI 1.01-1.13), brainstem location (OR 0.13, 95% CI 0.051-0.37), and lacunar (OR: 0.4, 95% CI 0.21-0.78) or undetermined etiology (OR: 0.4, 95% CI 0.22-0.78) remained independently associated. CONCLUSION: DWI detects AIS accurately; the positivity of these evaluations in the ER is associated only with NIHSS on admission, time to DWI, brainstem location, and AIS etiology. PMID- 29789896 TI - An offline technique to evaluate residual motion of the diaphragm during deep inspiratory breath-hold from cone-beam CT datasets. AB - PURPOSE: In radiation therapy, the computer-assisted deep inspiration breath-hold (DIBH) technique is one approach to deal with respiratory motion of tumors in the lung, liver, or upper abdomen. However, inter- and intra-breath-hold deviations from an optimal static tumor position might occur. A novel method is presented to noninvasively measure the diaphragm position and thus estimate its residual deviation (as surrogate for the tumor position) based on cone-beam computed tomography (CBCT) projection data using active breathing control during acquisition. METHODS: The diaphragm dome (DD) position relative to the isocenter of a linear accelerator is known from the static (DIBH) planning CT. A ball bearing phantom (BB) is placed at this position, a CBCT dataset is acquired, and in each projection the position of the projected BB is determined automatically based on thresholding. The position of the DD is determined manually in CBCT projections of a patient. The distance between DD and BB (ideal static setting) in craniocaudal direction is calculated for a given angle based on the distance in the projection plane and the relative position of the BB referring to the source and the detector. An angle-dependent correction factor is introduced which takes this geometrical setting into account. The accuracy of the method is assessed. RESULTS: The method allows a CBCT projection-based estimation of the deviation between the DD and its optimal position as defined in the planning CT, i.e., the residual motion of the DD can be assessed. The error of this estimation is 2.2 mm in craniocaudal direction. CONCLUSIONS: The developed method allows an offline estimation of the inspiration depth (inter- and intra-breath-hold) over time. It will be useful as a reference for comparison to other methods of residual motion estimation, e.g., surface scanning. PMID- 29789900 TI - Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction. AB - Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 +/- 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (beta = - 0.239, p = 0.011), heart rate (beta = 0.216, p = 0.021), LV mass index (beta = 0.231, p = 0.020), and E to e' ratio (beta = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers. PMID- 29789901 TI - Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection. AB - Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy. Gene expression analyses of alpha-smooth muscle actin, endothelial CD31 antigen, alpha-cardiac actin, matrix metalloprotease-2 (MMP2) and tissue inhibitor of matrix metalloprotease-1 (TIMP1) was performed on cDNA obtained from either microdissected neoplastic cells or whole tumor sections. We found very little or absent CD31 and alpha-Smooth Muscle Actin expression in the microdissected cells as compared to the whole tumors, whereas TIMP1 and MMP2 genes were highly expressed in both ones, greater levels being found in patients with embolic phenomena. alpha-Cardiac Actin was not detected. Confocal microscopy disclosed two different signals corresponding to calretinin-positive myxoma cells and to endothelial CD31-positive cells, respectively. In conclusion, the neoplastic (lepidic) cells showed a distinct gene expression pattern and no consistent overlapping with endothelial and smooth muscle cells or cardiac myocytes; the expression of TIMP1 and MMP2 might be related to clinical presentation; larger series studies using also systematic transcriptome analysis might be useful to confirm the present results. PMID- 29789902 TI - Association of plasma pentraxin-3 levels with coronary risk factors and the lipid profile: a cross-sectional study in Japanese patients with stable angina pectoris. AB - The aim of this study was to evaluate the relationships among the traditional risk factors, lipid profile, and pentraxin-3 in stable angina (SAP). Plasma pentraxin-3 and serum LDL, HDL, and high-sensitivity CRP levels were measured in 163 SAP and 28 non-coronary artery disease (CAD) patients. Their relationships with five risk factors, hypertension (HT), dyslipidemia (DL), diabetes mellitus (DM), obesity (body mass index: BMI > 25 kg/m2), and high age (> 75 years), were evaluated. No significant difference was observed in the pentraxin-3 level between patients in SAP and in non-CAD [2.1 (1.4-3.5) ng/ml versus off 2.6 (1.6 3.8) ng/ml, P = 0.56). In SAP patients, pentraxin-3 levels decreased with more risk factors, according to the number of 3 traditional risk factors (HT, DL, and DM) and the number of 5 expanded risk factors (HT, DL, DM, obesity, and high age) (P for trend = 0.01 and 0.05, respectively). Pentraxin-3 showed a positive association with HDL (rs = 0.229; P = 0.050) and an inverse association with LDL (rs = - 0.224; P = 0.045). On multiple logistic regression, the number of 3 traditional risk factors was a significant predictor of pentraxin-3 levels (odds ratio = 0.444; 95% confidence interval 0.205-0.963, P = 0.040) in SAP patients. In SAP patients, the cardiovascular risk factor burden remained a negative impact on pentraxin-3 levels after multivariate analysis, suggesting that they have distinct roles in atherosclerosis.Trial registration: UMIN000023837. PMID- 29789904 TI - Revision knee arthroplasty with rotating hinge systems in patients with gross ligament instability. AB - PURPOSE: The clinical and radiographic outcomes after revision total knee arthroplasty (TKA) for instability with two rotating hinge knee prostheses were compared. METHODS: Fifty-one patients revised for TKA instability were prospectively randomized to either the Link Endo-Model (N = 26) or the EnduRo (N = 25). Clinical and radiographic outcome scores were compared pre-operatively and at 12 months' follow-up. Failure mechanisms were recorded. RESULTS: Age, BMI, operation, and tourniquet-time did not differ significantly between groups. Radiographic evaluation demonstrated correct implant alignment. The Endo-Model was implanted with a higher slope (p = 0.0001) and the mechanical lower extremity axis was straighter (p = 0.0323). Except for the patient function Knee Society Score and the Physical Health Component Summary Score in the EnduRo group, all clinical scores (range of motion/knee function Knee Society Score/Oxford Knee Score/Visual Analog Scale/Mental Health Component Summary Score) improved significantly for both prosthesis designs during the follow-up period. The Visual Analog Scale and Mental Health Component Summary score were significantly better (p = 0.045 and p = 0.0148) in the Endo-Model group at the 12 months' follow-up. In the EnduRo group 2 patients (8%) and in the Endo-Model group 1 patient (3.8%) had to be revised for infection. CONCLUSION: Both prosthetic designs provide significant improvement in pain and function scores after TKA revision for gross instability. We found slight advantages in favor of the Endo-Model; however, no design yielded superior results throughout the study. PMID- 29789903 TI - Stabilization of symptomatic carotid atherosclerotic plaques by statins: a clinico-pathological analysis. AB - Human and animal studies have revealed a stabilization of atherosclerotic plaques by statins. However, the stabilization of human carotid plaques has not been thoroughly described pathologically. This analysis explored the relationship between statin therapy and plaque stability in carotid endarterectomy (CEA) specimens. We analyzed specimens harvested between May 2015 and February 2017, from 79 consecutive patients presenting with > 70% carotid artery stenoses, of whom 66 were untreated (group 1) and 13 treated (group 2) with a statin. Immunohistochemistry was performed, using an endothelial specific antibody to CD31, CD34 and platelet derived growth factor receptor-beta. The prevalence of plaque ruptures (P = 0.009), lumen thrombi (P = 0.009), inflammatory cells (P = 0.008), intraplaque hemorrhages (P = 0.030) and intraplaque microvessels (P < 0.001) was significantly lower in group 2 than in group 1. Among 66 patients presenting with strokes and infarct sizes > 1.0 cm3 on magnetic resonance imaging, the mean infarct volume was significantly smaller (P = 0.031) in group 2 (4.2 +/- 2.5 cm3) than in group 1 (8.2 +/- 7.1 cm3). The difference in mean concentration of low-density lipoprotein cholesterol between group 1 (121 +/- 32 mg/dl) and group 2 (105 +/- 37 mg/dl) was non-significant (P = 0.118). This analysis of plaques harvested from patients undergoing CEA suggests that statin therapy mitigates the plaque instability, which, in patients presenting with strokes, might decrease infarct volume. PMID- 29789905 TI - Pre-operative MRI staging of endometrial cancer in a multicentre cancer network: can we match single centre study results? AB - OBJECTIVES: To evaluate the staging accuracy of magnetic resonance imaging (MRI) for endometrial cancer in daily practice over a 3-year period at a tertiary referral centre receiving scans from a large number of hospitals with varying protocols. To compare these daily practice results to published data from single centre studies. METHODS: After ethical approval, MRI staging records for 270 studies from nine network and three centre hospitals were retrospectively collected and compared with final operative histopathology. The International Federation of Gynaecology and Obstetrics (FIGO) stage, depth of invasion assessment and cervical stromal invasion were analysed and reasons for discrepancies reviewed. RESULTS: MRI-based complete FIGO stage was fully concordant with histopathology in 65.6%. MRI accuracy for depth of myometrial invasion and cervical stromal invasion was 73.3% and 89.3% respectively. Our results did not match the high accuracy previously reported in studies based on single centres. CONCLUSIONS: Published MRI staging accuracy from small single centre studies were not replicated in a tertiary referral centre receiving scans with heterogeneous protocols over a 3-year period. These results highlight the challenges faced in daily practice and may reflect achievable and realistic MRI staging accuracies in large rapid throughput referral networks. Adherence to standardised high-quality protocols may help to improve future results. KEY POINTS: * Three-year MRI-staging accuracy for endometrial cancer in a multicentre cancer network * Daily practice MRI-staging accuracy did not meet results of single-centre studies * Large scale cancer network MRI-staging accuracies should be further evaluated * Treatment recommendations should be based on achievable MRI-staging accuracies. PMID- 29789906 TI - Percutaneous intentional intra-luminal-assisted recanalization (PILAR technique) of challenging chronic total occlusions using a high-frequency vibration device. AB - OBJECTIVES: Recanalization of peripheral chronic total occlusions (CTO) is technically challenging especially in cases of in-stent and/or pre-stent and heavily calcified lesions. A high-frequency vibrational device (HFVD) was first used as a secondary-intention device in CTO recanalizations when they were refractory to a guidewire. The aim of this study was to assess the safety and efficacy of the HFVD as a first-line treatment for challenging CTOs and thus to define the percutaneous intentional intraluminal-assisted recanalization (PILAR) technique. METHODS: Fifty-two patients were treated with the HFVD. Only challenging CTOs were included: 7 pre-stent, 7 in-stent, and 38 highly calcified CTOs. Technical success was defined as the ability to cross the CTO using the HFVD. Secondary outcome was defined as successful intraluminal crossing. Safety endpoints were procedure-related thromboembolism or perforation. Patients were followed up at 3 months and 1 year. RESULTS: The technical success rate for recanalization was 90%, of which 83% were intraluminal. The mean recanalized length was 91 +/- 44 mm. One thromboembolic complication occurred, which was subsequently treated with thromboaspiration. Three-month and 1-year primary patency rates were 92% and 79%, respectively. CONCLUSIONS: HFVD-based PILAR is a safe and effective technique for in-stent or pre-stent CTO recanalization of long and calcified lesions. KEY POINTS: * Intraluminal recanalization is the preferred procedure in heavily calcified or pre-/in-stent CTO. * First-line use of assisted intraluminal recanalization for CTO defines the PILAR technique. * HFVD-based PILAR is safe and provides a high success rate for challenging CTO recanalization. PMID- 29789907 TI - Can quantitative iodine parameters on DECT replace perfusion CT parameters in colorectal cancers? AB - OBJECTIVES: To determine the correlation between iodine concentrations derived from dual-energy CT (DECT) and perfusion CT (PCT) parameters in patients with pathologically proven colorectal cancers (CRC) and to evaluate their reproducibility and respective radiation exposures. METHODS: Institutional review board approval and written informed consents were obtained for this study. Forty one patients with CRCs who underwent same-day DECT and PCT were prospectively enrolled. Three radiologists independently analyzed the iodine concentration of the tumors and iodine ratios [ratio of lesion to aorta (IRa) or to infrarenal IVC (IRv)] from DECT as well as blood flow (BF), blood volume (BV), permeability (PMB), and mean transit time (MTT) from PCT. Pearson R and linear correlation, paired t-test, and intraclass correlation coefficients (ICCs) were used. RESULTS: Significant correlations were found between iodine parameters from DECT and PCT parameters: iodine concentration of tumors and BV (r = 0.32, p = 0.04), PMB (r = 0.34, p = 0.03), and MTT (r = -0.38, p = 0.02); iodine ratio (IRa) and MTT (r = 0.32, p = 0.04); iodine ratio (IRv) and BF (r = 0.32, p = 0.04) and PMB (r = 0.44, p = <0.01). DECT showed better intra- and interobserver agreements (ICC = 0.98, 0.90 in iodine concentration; 0.98, 0.91 in IRa; and 0.91, 0.93 in IRv, respectively) than PCT (ICC = 0.90, 0.78 in BF; 0.82, 0.76 in BV; 0.75, 0.75 in PMB; 0.64, 0.79 in MTT, respectively). As for radiation dosage, CTDIvol and DLP in DECT (10.48 +/- 1.84 mGy and 519.7 +/- 116.7 mGy.cm) were significantly lower than those of PCT (75.76 mGy and 911 mGy.cm) (p < 0.01). CONCLUSION: Iodine parameters from DECT are significantly correlated with PCT parameters, but have higher intra- and interobserver agreements and lower radiation exposure. KEY POINTS: * Quantitative iodine concentrations from DECT are significantly correlated with perfusion CT parameters. * Intra- and interobserver agreements of DECT are better than those of perfusion CT. * Effective radiation doses of DECT are significantly lower than those of perfusion CT. * DECT can be used as an alternative to perfusion CT with lower radiation doses. PMID- 29789908 TI - Triple-rule-out CT angiography using two axial scans with 16 cm wide-detector for radiation dose reduction. AB - OBJECTIVE: To explore the use of two consecutive axial scans in triple-rule-out (TRO) examination on a 16 cm wide-detector CT for radiation dose reduction. MATERIALS AND METHODS: Sixty TRO patients were assigned to either study group (Group A, n = 30) or control group (Group B, n = 30). Group A used a two-phasic contrast injection: 25mgI/kg/s for 12 s in 1st and at 3.0 ml/s injection rate for 7 s in 2nd phase. The pulmonary artery, coronary artery and aorta were scanned in succession with two axial scans using smart-coverage technique. Group B used the conventional protocol of scanning pulmonary arteries first in helical, followed by coronary arteries in axial and aorta in helical mode with contrast injection of 25mgI/kg/s for 14 s. All images were reconstructed with 80% ASIR-V. The qualitative and quantitative image assessment and effective dose of the two groups were statistically compared. RESULTS: The demographic data and quantitative measurements and qualitative image scores between the two groups were statistically the same (p > 0.05). However, Group A reduced radiation dose by 52% (2.67 +/- 0.98 mSv vs. 5.65 +/- 1.37 mSv) (p < 0.001). CONCLUSION: Using two consecutive axial scans in triple-rule-out on a 16 cm wide-detector CT reduces radiation dose while maintaining image quality compared with the conventional TRO protocol. KEY POINTS: * Triple-rule-out can be performed with two-axial scans on a wide-detector CT system. * TRO with two-axial scans maintain image quality compared with conventional protocol. * TRO with two-axial scans reduces 52% radiation dose over conventional protocol. PMID- 29789909 TI - Fast 3-T MR-guided transrectal prostate biopsy using an in-room tablet device for needle guide alignment: a feasibility study. AB - OBJECTIVES: To assess the feasibility of adding a tablet device inside the scanner room to assist needle-guide alignment during magnetic resonance (MR) guided transrectal prostate biopsy. METHODS: Twenty patients with one cancer suspicious region (CSR) with PI-RADS score >= 4 on diagnostic multiparametric MRI were prospectively enrolled. Two orthogonal scan planes of an MR fluoroscopy sequence (~3 images/s) were aligned to the CSR and needle-guide pivoting point. Targeting was achieved by manipulating the needle-guide under MR fluoroscopy feedback on the in-room tablet device. Technical feasibility and targeting success were assessed. Complications and biopsy procedure times were also recorded. RESULTS: Needle-guide alignment with the in-room tablet device was technically successful in all patients and allowed sampling after a single alignment step in 19/20 (95%) CSRs (median size 14 mm, range: 4-45). Biopsy cores contained cancer in 18/20 patients. There were no per-procedural or post-biopsy complications. Using the tablet device, the mean time to first biopsy was 5.8 +/- 1.0 min and the mean total procedure time was 23.7 +/- 4.1 min. CONCLUSIONS: Use of an in-room tablet device to assist needle-guide alignment was feasible and safe during MR-guided transrectal prostate biopsy. Initial experience indicates potential for procedure time reduction. KEY POINTS: * Performing MR-guided prostate biopsy using an in-room tablet device is feasible. * CSRs could be sampled after a single alignment step in 19/20 patients. * The mean procedure time for biopsy with the tablet device was 23.7 min. PMID- 29789910 TI - A radiopaque 3D printed, anthropomorphic phantom for simulation of CT-guided procedures. AB - OBJECTIVES: To develop an anthropomorphic phantom closely mimicking patient anatomy and to evaluate the phantom for the simulation of computed tomography (CT)-guided procedures. METHODS: Patient CT images were printed with aqueous potassium iodide solution (1 g/mL) on paper. The printed paper sheets were stacked in alternation with 1-mm thick polyethylene foam layers, cut to the patient shape and glued together to create an anthropomorphic abdomen phantom. Ten interventional radiologists performed periradicular infiltration on the phantom and rated the phantom procedure regarding different aspects of suitability for simulating CT-guided procedures. RESULTS: Radiopaque printing in combination with polyethylene foam layers achieved a phantom with detailed patient anatomy that allowed needle placement. CT-guided periradicular infiltration on the phantom was rated highly realistic for simulation of anatomy, needle navigation and overall course of the procedure. Haptics were rated as intermediately realistic. Participants strongly agreed that the phantom was suitable for training and learning purposes. CONCLUSIONS: A radiopaque 3D printed, anthropomorphic phantom provides a realistic platform for the simulation of CT-guided procedures. Future work will focus on application for training and procedure optimisation. KEY POINTS: * Radiopaque 3D printing combined with polyethylene foam achieves patient phantoms for CT-guided procedures. * Radiopaque 3D printed, anthropomorphic phantoms allow realistic simulation of CT guided procedures. * Realistic visual guidance is a key aspect in simulation of CT-guided procedures. * Three-dimensional printed phantoms provide a platform for training and optimisation of CT-guided procedures. PMID- 29789911 TI - The role of core needle biopsy in the diagnosis of initially detected thyroid nodules: a systematic review and meta-analysis. AB - OBJECTIVES: To systematically review the published literature and evaluate the efficacy and safety of core needle biopsy (CNB) for initially detected thyroid nodules. METHODS: The Ovid-MEDLINE and Embase databases were searched for studies evaluating CNB for the diagnosis of initially detected thyroid nodules. A meta analysis was performed to evaluate non-diagnostic results, inconclusive results and diagnostic accuracy for a diagnosis of malignancy with CNB. To overcome heterogeneity, multiple subgroup analyses were performed. The complication rate was also evaluated. RESULTS: Thirteen eligible studies, which included a total sample size of 9,166 patients with 13,585 nodules, were included. The pooled proportions were 3.5% (95% CI 2.4-5.1) for non-diagnostic results and 13.8% (95% CI 9.1-20.3) for inconclusive results. Considerable heterogeneity was observed among the studies in terms of the pooled proportions for CNB (I2=92.9%, 97%). With regard to the diagnostic performance for malignancy, the sensitivity was 80% (95% CI 75-85) and the specificity was 100% (95% CI 93-100). Only two major complications of CNB were observed. CONCLUSIONS: CNB demonstrates a low non diagnostic result rate and high diagnostic accuracy for initially detected thyroid nodules and a low major complication rate. These findings indicate that CNB may be a feasible diagnostic tool for patients with initially detected thyroid nodules. KEY POINTS: CNB demonstrates high diagnostic accuracy for initially detected thyroid nodules. CNB demonstrates a low major complication rate. CNB may be a feasible diagnostic tool for patients with initially detected thyroid nodules. PMID- 29789912 TI - Meniscal pathologies on MRI correlate with increased bone tracer uptake in SPECT/CT. AB - OBJECTIVES: To assess the relationship of subchondral bone tracer uptake (BTU) on SPECT/CT and meniscal pathologies on MRI in patients with painful knees. METHODS: Twenty-five patients who had MRI and SPECT/CT within 3 months without knee surgery or grade >=3 cartilage lesions were prospectively included. Maximum values of each subchondral femorotibial area were quantified and a ratio was calculated in relation to a femoral shaft reference region, which represented the BTU background activity. Meniscal lesions were graded (intact/degeneration/tear) and meniscal extrusion (no/yes) was assessed using MRI by two musculoskeletal radiologists blinded to the SPECT/CT findings. One-tailed Spearman correlations served for statistics (p < 0.05). RESULTS: Knees with meniscal degeneration or tear showed a significantly higher BTU in the medial femorotibial compartment (p = 0.045) when compared to intact menisci. Meniscal degeneration was associated with an increased BTU in the lateral femorotibial compartment; however, this was not statistically significant (p = 0.143). Patients with an extruded meniscus showed significantly higher BTU compared to a non-extruded meniscus (p < 0.020). CONCLUSIONS: Medial femorotibial BTU in SPECT/CT was associated with meniscal pathologies. Highest BTU was found in patients with meniscal tears. SPECT/CT appears to be a useful imaging modality to identify patients with overloading or early osteoarthritis. KEY POINTS: * Meniscal degeneration and tears correlate significantly with increased BTU using SPECT/CT. * Medial meniscus extrusion is associated with an increased BTU in SPECT/CT. * SPECT/CT allows detection of overloading and early osteoarthritis. PMID- 29789913 TI - Ethylene vinyl alcohol copolymer for occlusion of specific portal branches during preoperative portal vein embolisation with n-butyl-cyanoacrylate. AB - OBJECTIVES: To evaluate the safety and efficacy of ethylene vinyl alcohol copolymer (EVOH) injection for selective occlusion of portal branches considered at risk for non-target embolisation during preoperative portal vein embolisation (PVE). METHODS: Twenty-nine patients (mean age, 57 +/- 17 years) submitted to PVE with n-butyl-cyanoacrylate (NBCA) and additional EVOH for selected portal branches were retrospectively analysed. Indications for the use of EVOH and the selected portal branches were evaluated. Degree of hypertrophy of the future liver remnant (FLR) and kinetic growth were assessed by CT volumetry performed before and 3-6 weeks after PVE. Clinical outcome and histopathological analysis of portal veins occluded with EVOH were reviewed. RESULTS: EVOH was indicated intraoperatively for embolisation of selected portal branches that the operator reported at risk to provoke non-target embolisation with NBCA. Indications for the use of EVOH were embolisation of segment IV (n = 21), embolisation of segmental portal branches with early bifurcation (n = 7) and PVE in a 1-year-old girl with cystic hamartomas. All targeted portal branches were successfully embolised. There were no cases with non-target embolisation by EVOH. The degree of hypertrophy of the FLR was 14.3 +/- 8.1% and the kinetic growth rate was 2.7 +/- 1.8% per week. CONCLUSION: EVOH is safe and effective for embolisation of selected portal vein branches considered at risk for non-target embolisation. KEY POINTS: * EVOH is another effective liquid embolic agent for preoperative PVE. * EVOH is relatively simple to handle with a minimal risk of non-target embolisation. * During PVE, some portal branches considered complicated to occlude with NBCA may be efficiently embolised with EVOH. PMID- 29789914 TI - Correlation-based perfusion mapping using time-resolved MR angiography: A feasibility study for patients with suspicions of steno-occlusive craniocervical arteries. AB - PURPOSE: To explore the feasibility of using correlation-based time-delay (CTD) maps produced from time-resolved MR angiography (TRMRA) to diagnose perfusion abnormalities in patients suspected to have steno-occlusive lesions in the craniocervical arteries. MATERIALS AND METHODS: Twenty-seven patients who were suspected to have steno-occlusive lesions in the craniocervical arteries underwent both TRMRA and brain single-photon emission computed tomography (SPECT). TRMRA was performed on the supra-aortic area after intravenous injection of a 0.03 mmol/kg gadolinium-based contrast agent. Time-to-peak (TTP) maps and CTD maps of the brain were automatically generated from TRMRA data, and their quality was assessed. Detection of perfusion abnormalities was compared between CTD maps and the time-series maximal intensity projection (MIP) images from TRMRA and TTP maps. Correlation coefficients between quantitative changes in SPECT and parametric maps for the abnormal perfusion areas were calculated. RESULTS: The CTD maps were of significantly superior quality than TTP maps (p < 0.01). For perfusion abnormality detection, CTD maps (kappa 0.84, 95% confidence interval [CI] 0.67-1.00) showed better agreement with SPECT than TTP maps (0.66, 0.46 0.85). For perfusion deficit detection, CTD maps showed higher accuracy (85.2%, 95% CI 66.3-95.8) than MIP images (66.7%, 46-83.5), with marginal significance (p = 0.07). In abnormal perfusion areas, correlation coefficients between SPECT and CTD (r = 0.74, 95% CI 0.34-0.91) were higher than those between SPECT and TTP (r = 0.66, 0.20-0.88). CONCLUSION: CTD maps generated from TRMRA were of high quality and offered good diagnostic performance for detecting perfusion abnormalities associated with steno-occlusive arterial lesions in the craniocervical area. KEY POINTS: * Generation of perfusion parametric maps from time-resolved MR angiography is clinically useful. * Correlation-based delay maps can be used to detect perfusion abnormalities associated with steno-occlusive craniocervical arteries. * Estimation of correlation-based delay is robust for low signal-to-noise 4D MR data. PMID- 29789915 TI - A Potential Diagnostic Approach for Foetal Long-QT Syndrome, Developed and Validated in Children. AB - In patients with Long-QT Syndrome (LQTS), mechanical abnormalities have been described. Recognition of these abnormalities could potentially be used in the diagnosis of LQTS, especially in the foetus where an ECG is not available and DNA analysis is invasive. We aimed to develop and validate a marker for these mechanical abnormalities in children and to test its feasibility in foetuses as a proof of principle. We measured the myocardial contraction duration using colour Tissue Doppler Imaging (cTDI) in 41 LQTS children and age- and gender-matched controls. Children were chosen to develop and validate the measurement of the myocardial contraction duration, due to the availability of a simultaneously recorded ECG. Feasibility of this measurement in foetuses was tested in an additional pilot study among seven LQTS foetuses and eight controls. LQTS children had a longer myocardial contraction duration compared to controls, while there was no statistical difference in heart rate. Measuring the myocardial contraction duration in children had a high inter- and intra-observer validity and reliably correlated with the QT-interval. There was an area under the curve (AUC) of 0.71, and the optimal cut-off value showed an especially high specificity in diagnosing LQTS. Measuring the myocardial contraction duration was possible in all foetuses and had a high inter- and intra-observer validity (ICC = 0.71 and ICC = 0.88, respectively). LQTS foetuses seemed to have a longer myocardial contraction duration compared to controls. Therefore, a prolonged contraction duration may be a potential marker for the prenatal diagnosis of LQTS in the future. Further studies are required to support the measurement of the myocardial contraction duration as a diagnostic approach for foetal LQTS. PMID- 29789917 TI - Comparison of Clinical Profiles in Patients with Protein-Losing Enteropathy With and Without Fontan Circulation. AB - Protein-losing enteropathy (PLE) is a life-threatening complication in patients following the Fontan operation. However, PLE also develops in some patients with congenital heart disease (CHD) after biventricular repair (BVR). This study compared clinical profiles of PLE patients following the Fontan operation with those after BVR. We retrospectively reviewed clinical charts of postoperative CHD patients with PLE. The study population comprised 42 PLE patients (14BVR, 28Fontan). Postoperative follow-up period until onset was significantly shorter in the Fontan group than in the BVR group (14 +/- 2 vs. 8 +/- 1 years, p = 0.02), while there was no difference in PLE onset age between groups. Furthermore, there were no differences in prevalence of clinically relevant arrhythmias, cardiac output, or central venous pressure between the two groups at PLE onset. Percentage of structural lesions (valve regurgitation and/or stenotic lesions) responsible for development of PLE and ventricular end-diastolic pressure were higher in the BVR group than in the Fontan group (93 vs. 50%, p < 0.01), (13.4 +/ 6.3 vs. 7.5 +/- 4.1, p < 0.0001). Catheter intervention was applied in 2Fontan and 6BVR patients, while surgical intervention was required in 8BVR and 7Fontan patients. Of these, catheter intervention was effective in 2 (25%, 1Fontan, 1BVR) and surgical intervention was effective in 4 (26.7%, 1Fontan, 3BVR). Only one patient (5.3%) improved without intervention. Complete PLE remission rate was higher in the BVR group than in the Fontan group (38 vs. 7%, p = 0.02). During follow-up, death of 2 BVR and 8 Fontan patients occurred. There were no group differences in 5- to 10-year survival rates after PLE onset (81 vs. 81%, BVR, 81 vs. 66%, Fontan). Although BVR patients may have greater chance of PLE remission when compared with those exhibiting Fontan pathophysiology, mortality in PLE-CHD patients was significantly high regardless of postoperative hemodynamics. PMID- 29789916 TI - Two-Dimensional Speckle Tracking Echocardiography-Derived Strain Measurements in Survivors of Childhood Cancer on Angiotensin Converting Enzyme Inhibition or Receptor Blockade. AB - Speckle tracking echocardiography (STE)-derived strain indices are believed to detect early cardiac dysfunction in survivors of childhood cancer and have potential to identify patients who may benefit from early heart failure treatment. However, effects of heart failure treatment on STE-derived strain measurements in this population are unknown. The aim of this study was to assess STE-derived strain measurements in survivors of childhood cancer treated with angiotensin converting enzyme inhibition or receptor blockade (ACEi/ARB). Two dimensional speckle tracking analysis was retrospectively performed on echocardiograms from childhood cancer survivors before and during therapy with ACEi/ARB. Global left ventricular longitudinal and circumferential strain (GLS and GCS) and strain rates (LSR and CSR) were assessed and correlated with conventional echocardiographic measures of function. In 22 childhood cancer survivors (median age: 14.8, range 6.4-21.6 years), mean GLS (- 13.83 +/- 0.74% to - 15.94 +/- 0.74%, p = 0.002), GCS (- 18.79 +/- 1.21% to - 20.74 +/- 0.84%, p = 0.027), LSR (- 0.78 +/- 0.04 to - 0.88 +/- 0.04 s-1, p = 0.022), and CSR (- 1.08 +/- 0.07 to - 1.21 +/- 0.06 s-1, p = 0.027) improved on therapy. Improvement in GLS was maintained for greater than 1 year on ACEi/ARB (p = 0.02). Measures of strain and strain rate correlated with standard echocardiographic measures of function and were reproducible. These findings support the use of ACEi/ARB to treat post-chemotherapy-related cardiovascular changes in childhood cancer survivors, provide proof-of-concept that STE-derived strain and strain rate may be used to reliably monitor cardiac function during therapy, and support continued investigation into the clinical benefit of strain measurements in this population. PMID- 29789918 TI - Recent Experience and Follow-Up After Surgical Closure of Secundum Atrial Septal Defect in 120 Children. AB - While percutaneous catheter closure proves an effective treatment for secundum atrial septal defect (ASD2), some child patients require surgical closure. We assessed the risks associated with isolated surgical ASD2 closure by reviewing the outcomes of 120 children operated on between 1999 and 2011 (mean age 4.6 +/- 3.9 years, mean weight 17 +/- 12 kg). Direct sutures were performed in 4% and patch closures in 96%. The mean cardiopulmonary bypass duration was 38 +/- 14 min, aortic cross-clamp time 19 +/- 9 min, intensive care unit length of stay 1.6 +/- 1.1 days, hospital stay 11.2 +/- 5.1 days. There were no complications in 60 patients (50%) and major complications in 8 (6.7%), with 1 patient (0.8%) dying of pneumonia-induced sepsis, 2 (1.7%) requiring revision surgery, 3 (2.5%) requiring invasive treatment (2 pericardial drainage, 1 successful resuscitation), and 2 (1.7%) presenting thromboembolisms (1 cerebral stroke, 1 cardiac thrombus). In hospital minor complications occurred in 22 patients: 17 pericardial effusions (15%), 15 infections requiring treatment (12.5%), 1 sternal instability (0.8%), 4 anemias requiring transfusion (3.3%), 7 pulmonary atelectasis (6%), and 2 post-extubation glottis edema (1.7%). At early outpatient follow-up, complications occurred in 21 patients: 16 (13.3%) pericardial effusions, 4 (3.3%) infections requiring treatment, and 3 (2.5%) keloid scarring. No complications occurred during long-term follow-up. In line with published data, mortality was low (0.8%), yet major complications (6.7%) were more common in these cases than those following percutaneous ASD2 closure. Minor complications were frequent (43%) with no long-term sequelae. PMID- 29789919 TI - Biomarkers of muscle damage increased in anterolateral compared to direct lateral approach to the hip in hemiarthroplasty: no correlation with clinical outcome : Short-term analysis of secondary outcomes from a randomized clinical trial in patients with a displaced femoral neck fracture. AB - : In this study, we found elevated levels of serum CK in the anterolateral approach to the hip compared to the direct lateral approach in patients with a displaced femoral neck fracture. No correlation was found between levels of CK and functional outcomes. INTRODUCTION: To compare increase in serum creatine kinase (CK) and its association with functional outcome between the muscle sparing anterolateral approach and the direct lateral approach to the hip in patients with displaced femoral neck fracture (FNF). METHODS: In this randomized trial, we enrolled eligible patients between 70 and 90 years of age with FNF. Patients were allocated to an uncemented hemiarthroplasty inserted through a direct lateral or an anterolateral approach. The primary endpoints were pain and patient satisfaction assessed by the Visual Analogue Scale (VAS). Among secondary endpoints was increase in CK at 24 and 48 h compared to baseline and its association with surgical parameters, Timed up and Go Test (TUG), Harris Hip Score (HHS), and the presence of a Trendelenburg sign using correlation analysis. This paper reports on increase in serum CK and its association with functional outcome. RESULTS: At 24 h, there was a mean increase from baseline in total CK of 228 U/L (95% CI 187 to 269; P < 0.001). There was a difference between groups at 24 h in CK increase with higher levels in the anterolateral group (mean difference 80 U/L; 95% CI - 0.5 to 162; P = 0.05). Likewise, at 48 h, there was a mean difference of 117 U/L (95% CI 22 to 212; P = 0.01). No correlation was found between CK values and functional assessments. CONCLUSIONS: Compared with the direct lateral approach, the anterolateral approach yielded higher levels of postoperative CK. However, there was no correlation between levels of CK and functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02028468. PMID- 29789920 TI - Iatrogenic dural tear in endoscopic lumbar spinal surgery: full endoscopic dural suture repair (Youn's technique). AB - BACKGROUND: With the advancement of minimally invasive spinal surgery, endoscopic lumbar decompression has been widely used for the treatment of degenerative lumbar spinal diseases. Iatrogenic dural tear is a relatively common complication in endoscopic lumbar spinal surgery. The golden standard of treatment for iatrogenic dural tear is immediate open conversion and direct repair under microscopic visualization. Recently, most of endoscopic spinal surgery is performed under local anesthesia. So, conversion to open surgery is very embarrassing situation because of the need of additional general anesthesia. But, direct endoscopic dural repair is very difficult procedure due to the limitation of manipulation. No report showed direct dural suture under full endoscopic situation. PURPOSE: The purpose of this surgical technique is to provide a method of full endoscopic dural suture repair without conversion to open surgery. PMID- 29789922 TI - Temperature affects phenological synchrony in a tree-killing bark beetle. AB - Phenological synchrony can promote population growth in species with positive density dependence. Variation among life stages in the thermal thresholds for development can foster phenological synchrony under thermal regimes that include frequent occurrence of temperatures between developmental thresholds. The southern pine beetle is an insect with positive density dependence that has recently undergone important shifts in population abundance at the northern extremes of their distribution. We evaluated the hypothesis that cooler winter temperatures in their northern range cause a convergence of the population life stage structure that leads to synchrony in spring flight phenology. We used a combination of approaches. First, in situ laboratory experiments demonstrated a threshold temperature for pupation that was greater than was required for larval development; rearing larvae at lower temperatures increased the pooling of individuals at the end stage of larval development and synchrony in adult emergence. Second, a development rate model showed a similar convergence of the majority of the population at the end stage of larval development when brood experienced the cooler temperatures of the northern region, but not with temperatures from the southern region, or as a null model. Finally, field trapping of wild beetles showed greater synchrony in the pine forests of New Jersey than in the warmer, historically occupied forests of Georgia and Mississippi. Given these results, pine-dominated forests in the northern edge of the southern pine beetle's range may experience more frequent occurrence of outbreaks, due to the positive feedbacks associated with a synchronous spring emergence of this insect. PMID- 29789921 TI - Intervertebral disc damage models in organ culture: a comparison of annulus fibrosus cross-incision versus punch model under complex loading. AB - PURPOSE: Comparison of two annulus fibrosus injury models that mimic intervertebral disc (IVD) herniation, enabling the study of IVD behaviour under three loading regimes in a bovine organ culture model. METHODS: An injury was induced by custom-designed cross-incision tool or a 2-mm biopsy punch in IVDs. Discs were cultured for 14 days under (1) complex (compression and torsion), (2) static, and (3) no load. Disc height, mitochondrial activity, DNA and glycosaminoglycan (GAG) contents, and disc stiffness under complex load were determined. Further, gene expression and histology analysis were performed. RESULTS: While both injury models did not change the compressional stiffness of IVDs, cross-incision decreased disc height under complex load. Moreover, under complex load, the biopsy punch injury induced down-regulation of several anabolic, catabol ic, and inflammatory genes, whereas cross-incision did not significantly differ from control discs. However, DNA and GAG contents were in the range of the healthy control discs for both injury models but did show lower contents under no load and static load. Injury side and contralateral side of the IVD showed a similar behaviour on the biochemical assays tested. CONCLUSION: Compressional stiffness, GAG and DNA contents, did not differ between injury models under complex load. This behaviour was partially attributed to the positive influence of complex loading on matrix regeneration and cell viability. However, disc height was reduced for the cross-incision. Relative gene expression changes of the inflammatory and anabolic genes for the biopsy punch approach might indicate that induced damage was too intense to trigger any inflammatory or repair response. These slides can be retrieved under Electronic Supplementary Material. PMID- 29789923 TI - The HAF2 protein shapes histone acetylation levels of PRR5 and LUX loci in Arabidopsis. AB - MAIN CONCLUSION: The histone acetyltransferase HAF2 facilitates H3 acetylation deposition at the PRR5 and LUX promoters to contribute to robust circadian oscillation. The circadian clock ensures synchronization of endogenous rhythmic processes with environmental cycles. Multi-layered regulation underlies precise circadian oscillation, and epigenetic regulation is emerging as a crucial scheme for robust circadian maintenance. Here, we report that HISTONE ACETYLTRANSFERASE OF THE TAFII250 FAMILY 2 (HAF2) is involved in circadian homeostasis. The HAF2 gene is activated at midday, and its temporal expression is shaped by CIRCADIAN CLOCK-ASSOCIATED 1. The midday-activated HAF2 protein stimulates H3 acetylation (H3ac) deposition at the PRR5 and LUX loci, contributing to establishment of the raising phase. These results indicate that epigenetic waves in circadian networks underlie temporal compartmentalization of circadian components and stable maintenance of circadian oscillation. PMID- 29789924 TI - Correction to: The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer. AB - Two corrections were made to the above publication following its original online publication on 4th May 2018. PMID- 29789925 TI - Associations of polymorphisms of CYP2D6 and CYP2C9 with early onset severe pre eclampsia and response to labetalol therapy. AB - PURPOSE: Early onset preeclampsia (PPE) contributes to life-threatening maternal complications and fetal demise. Pharmacogenomics is a precision medicine, and metabolizing enzymes responsive to antihypertensive remains understudied. The aim of this study was to evaluate the associations of polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with PPE and the relationship among CYP2D6, CYP2C9 polymorphisms and response to labetalol therapy. METHODS: Totally 105 gravidas diagnosed with PPE (case) and 103 healthy gravidas (control) were recruited between August 2013 and July 2016. Labetalol was given to control blood pressures (BP) with PPE. If labetalol administration alone did not exceed the mean dose and effectively controlled the BP, it would be considered to be valid (n = 75). Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686, and rs3892097) were analyzed by TaqMan PCR. Differences in the genotype and allele frequencies were compared between case-control groups, and the responsive and nonresponsive to labetalol in PPE. RESULTS: Out of six variants, only CC and CT genotypes of the CYP2D6 variants (rs28371725) in PPE were significantly higher than those in the control group [18.1% (19/105) vs 14.6% (15/103); 56.2% (59/105) vs 42.7% (44/103); chi2 = 6.707]. However, there were no differences in maternal age, diastolic pressure, BMI, BW, serum triglyceride, and creatinine were observed among women with CC, CT, or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P > 0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5 +/- 2.1) vs (29.5 +/- 1.8) and (29.8 +/- 2.2) weeks] and higher plasma albumin [(27.2 +/- 9.3) vs (20.3 +/- 10.4) and (22.5 +/- 7.4) g/L], but lower systolic pressure and 24 h urine protein (LSD test, all P < 0.05). The G allele frequency in CYP2D6 gene rs1065852 nonresponsive to labetalol group was higher than that in responsive labetalol group [93.3% (56/60) vs 76.0% (114/150), chi2 = 8.351, P = 0.004]. CONCLUSIONS: The polymorphism of CYP2D6 gene rs28371725 may be associated with PPE, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of PPE. PMID- 29789927 TI - Cellular components and circuitry of the presubiculum and its functional role in the head direction system. AB - Orientation in space is a fundamental cognitive process relying on brain-wide neuronal circuits. Many neurons in the presubiculum in the parahippocampal region encode head direction and each head direction cell selectively discharges when the animal faces a specific direction. Here, we attempt to link the current knowledge of afferent and efferent connectivity of the presubiculum to the processing of the head direction signal. We describe the cytoarchitecture of the presubicular six-layered cortex and the morphological and electrophysiological intrinsic properties of principal neurons and interneurons. While the presubicular head direction signal depends on synaptic input from thalamus, the intra- and interlaminar information flow in the microcircuit of the presubiculum may contribute to refine directional tuning. The interaction of a specific interneuron type, the Martinotti cells, with the excitatory pyramidal cells may maintain the head direction signal in the presubiculum with attractor-like properties. PMID- 29789926 TI - Patterns of platinum drug use in an acute care setting: a retrospective study. AB - PURPOSE: Platinum drugs have been in use in cancer treatment for more than 40 years, but little is known about the pattern of their use. The aim of this study was to examine the patterns of platinum drug use, with a secondary aim to describe the occurrence of dose reductions. METHODS: A retrospective analysis was conducted of oncology pharmacy dispensing records from a single hospital in Australia. Data related to drug choice, regimen and dose reductions were included in this study if the patient had received their last round of chemotherapy between November 2014 and July 2015. RESULTS: Of the 156 patients included in the study, 46% were dispensed a platinum drug during their treatment. The most commonly dispensed drugs were cisplatin (40%), carboplatin (40%) and oxaliplatin (15%), while some patients (5%) received more than one platinum drug. Dose reductions were more common in patients who were treated with a platinum drug (73%) compared with patients treated with non-platinum drugs (55%). The most common reason for a dose reduction was cytopenia. CONCLUSIONS: The findings suggest that platinum drugs remain one of the most commonly dispensed drugs to treat cancer patients and most patients receive a dose reduction during treatment. PMID- 29789928 TI - Effects of fundamental nutrient stresses on the lipid accumulation profiles in two diatom species Thalassiosira weissflogii and Chaetoceros muelleri. AB - Microalgae are considered as attractive feedstocks for biofuel production nowadays because of their high lipid contents and easy cultivation. In the present study, two diatoms, Thalassiosira weissflogii and Chaetoceros muelleri, were cultured under various nutrient-limitation conditions to explore their comprehensive lipid accumulation profiles for further commercialization. In T. weissflogii, the highest neutral lipid accumulation and highest lipid productivity (14.28 mg L-1 day-1) were both recorded under P-limitation. In C. muelleri, the highest lipid content (35.03% of dry cell weight), highest neutral lipid accumulation, and highest lipid productivity (29.07 mg L-1 day-1) were all recorded under N-limitation. Besides, the predominant fatty acids of T. weissflogii and C. muelleri were myristic acid (C14:0), palmitic acid (C16:0), and palmitoleic acid (C16:1), with the amounts of 58.4-74.4 and 74.1-87.7% of the total fatty acids, respectively. Moreover, nutrient limitations led to a lower proportion of polyunsaturated fatty acids (PUFA) than that of saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) in both species. The ratios of (SFA + MUFA) to PUFA were from 1.65 to 3.01 in T. weissflogii, and up to 3.61 to 8.59 in C. muelleri. Our results suggested the feasibility of C. muelleri as biodiesel feedstock due to its more suitable fatty acid composition and higher lipid productivity compared to T. weissflogii. PMID- 29789929 TI - Mechanistic simulation of batch acetone-butanol-ethanol (ABE) fermentation with in situ gas stripping using Aspen PlusTM. AB - Process simulations of batch fermentations with in situ product separation traditionally decouple these interdependent steps by simulating a separate "steady state" continuous fermentation and separation units. In this study, an integrated batch fermentation and separation process was simulated for a model system of acetone-butanol-ethanol (ABE) fermentation with in situ gas stripping, such that the fermentation kinetics are linked in real-time to the gas stripping process. A time-dependent cell growth, substrate utilization, and product production is translated to an Aspen Plus batch reactor. This approach capitalizes on the phase equilibria calculations of Aspen Plus to predict the effect of stripping on the ABE fermentation kinetics. The product profiles of the integrated fermentation and separation are shown to be sensitive to gas flow rate, unlike separate steady state fermentation and separation simulations. This study demonstrates the importance of coupled fermentation and separation simulation approaches for the systematic analyses of unsteady state processes. PMID- 29789930 TI - Introduction of a modified double-lumen tube. PMID- 29789931 TI - Relationship between fresh frozen plasma to packed red blood cell transfusion ratio and mortality in cardiovascular surgery. AB - PURPOSE: The aim of this study was to examine the relationship between FFP (fresh frozen plasma)/pRBC (packed red blood cell) transfusion ratio and outcomes in patients undergoing cardiovascular surgery. METHODS: This is a single center retrospective cohort study performed in a cardiovascular center. Patients undergoing cardiovascular surgery between January 2012 and October 2016 with or without massive transfusion (n = 1453). Patients' outcomes were compared based on FFP/pRBC transfusion ratio (FFP/pRBC > 1 or FFP/pRBC <= 1). RESULTS: In hospital mortality and rate of stroke and myocardial infarction was significantly higher in patients with less than 1 of FFP/pRBC transfusion ratio only in patients with massive transfusion (3.0 vs 8.8%, p = 0.001; 0.7 vs 6.4%, p < 0.001; 1.0 vs 3.2%, p = 0.047, respectively). CONCLUSIONS: Higher FFP/RBC ratio was associated with reduced risk of death, stroke and myocardial infarction only in patients with cardiovascular surgery receiving massive transfusion. Clinicians should be aware that judicious FFP replacement plays a critical role in the successful management of massive transfusion in cardiac surgery. PMID- 29789933 TI - Adequacy of usual macronutrient intake and macronutrient distribution in children and adolescents in Spain: A National Dietary Survey on the Child and Adolescent Population, ENALIA 2013-2014. AB - OBJECTIVES: To describe the nutritional profile and assess the National Dietary Survey on the Child and Adolescent Population project in Spain (ENALIA) regarding usual total energy and macronutrient intake. METHODS: A cross-sectional nationally representative sample of 1862 children and adolescents (age 6 months to 17) was surveyed between 2013 and 2014 following European methodology recommendations. Dietary information was collected using two methods, dietary records (for children from age 6 months to 9 years) and 24-h dietary recall (participants age 10 and older). Usual intake was estimated by correcting for within-person intake variance using the Iowa State University (ISU) method. A probability analysis was used to assess compliance with dietary reference intakes in the target population. RESULTS: Protein consumption in the age 1-3 group as a percentage of total energy exceeded the upper limit of the Acceptable Macronutrient Distribution Range (AMDR) by 4.7% for boys and 12.1% for girls. 42.9% of girls age 4-8 were under the lower limit of the AMDR for carbohydrates. 43.4% of boys and 46.9% of girls between 4 and 17 exceeded the AMDR in total fat intake, saturated fatty acids (SFAs) accounting for 12.3% of total energy. CONCLUSIONS: The results suggest that Spanish children and adolescents could improve macronutrient distribution by reducing fat and increasing carbohydrate intake across all age groups, and decreasing protein intake, especially in young children. PMID- 29789932 TI - The cognitive nuances of surprising events: exposure to unexpected stimuli elicits firing variations in neurons of the dorsal CA1 hippocampus. AB - The ability to recognize novel situations is among the most fascinating and vital of the brain functions. A hypothesis posits that encoding of novelty is prompted by failures in expectancy, according to computation matching incoming information with stored events. Thus, unexpected changes in context are detected within the hippocampus and transferred to downstream structures, eliciting the arousal of the dopamine system. Nevertheless, the precise locus of detection is a matter of debate. The dorsal CA1 hippocampus (dCA1) appears as an ideal candidate for operating a mismatch computation and discriminating the occurrence of diverse stimuli within the same environment. In this study, we sought to determine dCA1 neuronal firing during the experience of novel stimuli embedded in familiar contexts. We performed population recordings while head-fixed mice navigated virtual environments. Three stimuli were employed, namely a novel pattern of visual cues, an odor, and a reward with enhanced valence. The encounter of unexpected events elicited profound variations in dCA1 that were assessed both as opposite rate directions and altered network connectivity. When experienced in sequence, novel stimuli elicited specific responses that often exhibited cross sensitization. Short-latency, event-triggered responses were in accordance with the detection of novelty being computed within dCA1. We postulate that firing variations trigger neuronal disinhibition, and constitute a fundamental mechanism in the processing of unexpected events and in learning. Elucidating the mechanisms underlying detection and computation of novelty might help in understanding hippocampal-dependent cognitive dysfunctions associated with neuropathologies and psychiatric conditions. PMID- 29789934 TI - Induction prednisone dosing for childhood nephrotic syndrome: how low should we go? AB - BACKGROUND: Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. METHODS: This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid sparing agent (SSA). RESULTS: Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m2 respectively. Doses <= 2000 mg/m2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses <= 2500 mg/m2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in <= 3000 vs > 3000 mg/m2 doses. CONCLUSIONS: Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m2. Further prospective studies are warranted. PMID- 29789936 TI - Proposal of a form for the collection of videolaryngostroboscopy basic findings. AB - Videolaryngostroboscopy is a useful investigation required for a correct diagnosis of laryngeal diseases and voice disorders. We present a form for the collection of basic laryngostroboscopic findings, which provides for the evaluation of the classical six parameters codified by Hirano (symmetry and periodicity of glottic vibration, glottic closure, profile of vocal fold edge, amplitude of vocal fold vibration, mucosal wave) and six other parameters which we have included in the form for an essential and complete laryngostroboscopic evaluation (supraglottic framework behaviour, seat of phonatory vibration, vocal fold morphology and motility, level of the vocal fold, stops of vocal fold mucosa vibration). This form was created in 2002 during the elaboration of the protocol for the assessment of dysphonia of the Italian Society of Phoniatrics and Logopedics, which follows the guidelines of the European Laryngological Society published in 2001. We used this form for 15 years in our daily laryngological practice with great satisfaction. We propose a more detailed version of this form, which provides for drawings which show the various videolaryngostroboscopic findings, helping the laryngologist in the collection of videolaryngostroboscopic examination basic findings. PMID- 29789937 TI - Visual and auditory steady-state responses in attention-deficit/hyperactivity disorder. AB - We designed a study to investigate the patterns of the steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) in adolescents with attention-deficit/hyperactivity disorder (ADHD) when performing a motor response inhibition task. Thirty 12- to 18-year-old adolescents with ADHD and 30 healthy control adolescents underwent an electroencephalogram (EEG) examination during steady-state stimuli when performing a stop-signal task. Then, we calculated the amplitude and phase of the steady-state responses in both visual and auditory modalities. Results showed that adolescents with ADHD had a significantly poorer performance in the stop-signal task during both visual and auditory stimuli. The SSVEP amplitude of the ADHD group was larger than that of the healthy control group in most regions of the brain, whereas the ASSR amplitude of the ADHD group was smaller than that of the healthy control group in some brain regions (e.g., right hemisphere). In conclusion, poorer task performance (especially inattention) and neurophysiological results in ADHD demonstrate a possible impairment in the interconnection of the association cortices in the parietal and temporal lobes and the prefrontal cortex. Also, the motor control problems in ADHD may arise from neural deficits in the frontoparietal and occipitoparietal systems and other brain structures such as cerebellum. PMID- 29789935 TI - Potential use of stem cells as a therapy for cystinosis. AB - Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity. However, in the case of cystinosis, the defective protein is a transmembrane lysosomal protein, cystinosin. Thus, cystinosin cannot be secreted, and yet, we showed that HSPC transplantation can rescue disease phenotype in the mouse model of cystinosis. In this review, we are describing a different mechanism by which HSPC derived cells provide cystinosin to diseased cells within tissues, and how HSPC transplantation could be an effective one-time treatment to treat cystinosis but also other LSDs associated with a lysosomal transmembrane protein dysfunction. PMID- 29789938 TI - Meta-analysis of physical activity and effects of social function and quality of life on the physical activity in patients with schizophrenia. AB - Schizophrenia patients have increased mortality and morbidity, mainly due to premature cardiovascular disease resulting from decreased physical activity (PA). However, which PA intensity is impaired in the patients and how factors such as social function and quality of life (QoL) are related to decreased PA is unknown. To assess PA, social function and QoL, the International Physical Activity Questionnaire (IPAQ), Social Functioning Scale (SFS) and Schizophrenia Quality of Life Scale (SQLS), respectively, were used in 109 schizophrenia patients and 69 healthy subjects. A meta-analysis comparing PA intensities (vigorous, moderate and light) assessed by the single PA measurement between schizophrenia patients and healthy subjects after including our case-control sample was performed. Furthermore, the effects of social function and QoL on each level of PA intensity were investigated in patients and controls. The meta-analysis in 212 schizophrenia patients and 132 healthy subjects revealed that patients showed lower total PA, particularly vigorous PA, than controls (I2 = 0, Hedges' g = - 0.41, P = 2.80 * 10-4). The decreased total PA was correlated with impaired total SFS scores (beta = 0.24, P = 2.86 * 10-3), withdrawal (beta = 0.23, P = 3.74 * 10 3) and recreation (beta = 0.23, P = 3.49 * 10-3) without significant heterogeneity between patients and controls. In contrast, the decreased total PA was affected by low independence-performance (beta = 0.22, P = 0.034), employment/occupation (beta = 0.27, P = 8.74 * 10-3), psychosocial (beta = - 0.24, P = 0.021) and motivation/energy (beta = - 0.26, P = 0.013), but only in patients. Similar findings were obtained for vigorous PA but not moderate or light PA. Our findings suggest that the impaired vigorous PA in schizophrenia patients may be mediated by schizophrenia-specific factors of social functioning and QoL. Understanding these factors has important implications for increasing PA participation in schizophrenia patients. PMID- 29789939 TI - Effects of heat stress in the leaf mitotic cell cycle and chromosomes of four wine-producing grapevine varieties. AB - Grapevine varieties respond differentially to heat stress (HS). HS ultimately reduces the photosynthesis and respiratory performance. However, the HS effects in the leaf nuclei and mitotic cells of grapevine are barely known. This work intends to evaluate the HS effects in the leaf mitotic cell cycle and chromosomes of four wine-producing varieties: Touriga Franca (TF), Touriga Nacional (TN), Rabigato, and Viosinho. In vitro plants with 11 months were used in a stepwise acclimation and recovery (SAR) experimental setup comprising different phases: heat acclimation period (3 h-32 degrees C), extreme HS (1 h-42 degrees C), and two recovery periods (3 h-32 degrees C and 24 h-25 degrees C), and compared to control plants (maintained in vitro at 25 degrees C). At the end of each SAR phase, leaves were collected, fixed, and used for cell suspensions and chromosome preparations. Normal and abnormal interphase and mitotic cells were observed, scored, and statistically analyzed in all varieties and treatments (control and SAR phases). Different types of chromosomal anomalies in all mitotic phases, treatments, and varieties were found. In all varieties, the percentage of dividing cells with anomalies (%DCA) after extreme HS increased relative to control. TF and Viosinho were considered the most tolerant to HS. TF showed a gradual MI reduction from heat acclimation to HS and the lowest %DCA after HS and 24 h of recovery. Only Viosinho reached the control values after the long recovery period. Extrapolating these data to the field, we hypothesize that during consecutive hot summer days, the grapevine plants will not have time or capacity to recover from the mitotic anomalies caused by high temperatures. PMID- 29789940 TI - Postembryonic development of Arostrilepis microtis Gulyaev et Chechulin, 1997 (Eucestoda: Hymenolepididae) in springtails (Collembola: Entomobryidae). AB - The development of the metacestode stages of Arostrilepis microtis (Eucestoda: Hymenolepididae) studied on the basis of an experimental infection of springtails (Collembola: Entomobryidae) is described for the first time. A complete description of the ontogeny from oncosphere to fully a developed metacestode is given. The postembryonic development within the intermediate host includes one invagination. Cysts are without an anterior invagination pore, and the cercomer does not separate after the full maturation of larva. The comparison of morphology and maturation rate of larval cestodes of A. microtis with A. beringiensis and A. tenuicirrosa is presented. Cysticercoids of A. microtis are significantly larger and require a longer period of development than those of A. beringiensis and A. tenuicirrosa. PMID- 29789941 TI - New variants of porcine epidemic diarrhea virus with large deletions in the spike protein, identified in the United States, 2016-2017. AB - Four types of porcine epidemic diarrhea virus (PEDV) variants with a large deletion in the spike protein were detected, together with the original US PEDV, from pig fecal and oral fluid samples collected during 2016-2017 in the US. Two of the variants are similar to those identified in Japan: one contains a 194-aa deletion, the same as PEDV variant TTR-2/JPN/2014, while the other contains a 204 aa deletion, the same as PEDV variant JKa-292/CS1de204. Two new S1 NTD-del PEDV variants were found: one contains a 201-aa deletion located at residues 30-230 and the other contains a 202-aa deletion located at residues 24-225 of the S protein. This is the first report on coinfection of S1 NTD-del PEDV variants and the original US PEDV strain in US pigs, indicating that PEDV continues to evolve in pigs and might be responsible for disease pattern changes. PMID- 29789942 TI - Analysis of the complete genome sequence of a potyvirus from passion fruit suggests its taxonomic classification as a member of a new species. AB - The complete genomic sequence of a telosma mosaic virus (TeMV) isolate (named PasFru), identified in passion fruit in China, was determined. The entire RNA genome of PasFru comprises 10,049 nucleotides (nt) excluding the poly(A) tail and encodes a polyprotein of 3,173 amino acids (aa), flanked by 5' and 3' untranslated regions (UTR) of 276 and 251 nt, respectively. Compared with the previous TeMV isolate Hanoi from Telosma cordata, the only documented isolate with the entire genome sequence annotated, PasFru had an extra 87 nt and 89 aa residues at the 3'-end of 5'UTR and the N-terminus of the P1 protein, respectively, which contributed to the genome size difference between PasFru and Hanoi (10,049 nt versus 9,689 nt). Pairwise sequence comparisons showed that PasFru shares 73.6% nt and 80.9% aa sequence identity with the Hanoi isolate at the whole-genome and polyprotein level, respectively, and these values are below the corresponding threshold values for species demarcation in the family Potyviridae. These data suggest that TeMV-PasFru should be classified as a new member of the genus Potyvirus. PMID- 29789943 TI - Outcomes of viscocanalostomy and phaco-viscocanalostomy in patients with advanced glaucoma. AB - PURPOSE: To determine the medium-term outcomes for patients with advanced glaucoma undergoing viscocanalostomy. METHODS: All patients with advanced glaucoma (mean deviation (MD) - 12.00 dB or above) and patients with poor visual acuity secondary to advanced glaucoma which precluded formal visual field assessment undergoing viscocanalostomy (VC) and phaco-viscocanalostomy between 2010 and 2014 under the care of a single surgical team were included. Intraocular pressure (IOP), visual acuity (VA) and visual field outcomes were assessed from data prospectively collected into a surgical outcome database. Success was defined at two IOP cut-off points: IOP <= 21 and <= 16 mmHg with (qualified) or without (complete) medications. RESULTS: One hundred thirty-five patients were included. Mean IOP changed from 23.6 +/- 6.4 mmHg pre-operatively to 15.3, 15.8 and 14.8 mmHg at 1, 2 and 3 years, a change of 35, 33.5 and 39% respectively. Qualified success for an IOP <= 21 mmHg was achieved in 95.66, 90.6 and 80% and complete success in 52.5, 48.6 and 30.6% at year 1, 2 and 3. Qualified success for an IOP <= 16 mmHg was achieved in 66.6, 66.05 and 60% and complete success in 44.8, 37.6 and 30.6% at year 1, 2 and 3. The cumulative probability for achieving an IOP <= 21 mmHg with or without drops was 86.1, 81.4 and 81.4% at 12, 24 and 36 months. Eleven patients (8.1%) failed to achieve adequate IOP control and needed further surgical intervention. Eleven (8.1%) patients needed an intervention (Yag goniopuncture) following VC. Four patients (2.9%) had some post-operative complications, which resolved within 2 weeks following surgery. Nine patients (6.7%) lost more than 2 Snellen lines. There was no significant change in the MD across time points. CONCLUSION: Viscocanalostomy and viscocanalostomy combined with phacoemulsification is a safe and effective method of controlling IOP in the medium term in patients with advanced glaucoma. PMID- 29789944 TI - The association between age at menarche and later risk of gestational diabetes is mediated by insulin resistance. AB - AIMS: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic beta-cell function in pregnancy. METHODS: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic beta-cell function (HOMA B) at week 28 of pregnancy. RESULTS: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 * 10-4; quadratic term: p = 1.0 * 10-3; n = 889; overall model p = 8.1 * 10-3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: beta = -0.13, p = 5.2 * 10 4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with beta-cell function (HOMA B: beta = 0.11, p = 2.8 * 10-3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). CONCLUSIONS: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance. PMID- 29789945 TI - Remote monitoring of vibrational information in spider webs. AB - Spiders are fascinating model species to study information-acquisition strategies, with the web acting as an extension of the animal's body. Here, we compare the strategies of two orb-weaving spiders that acquire information through vibrations transmitted and filtered in the web. Whereas Araneus diadematus monitors web vibration directly on the web, Zygiella x-notata uses a signal thread to remotely monitor web vibration from a retreat, which gives added protection. We assess the implications of these two information-acquisition strategies on the quality of vibration information transfer, using laser Doppler vibrometry to measure vibrations of real webs and finite element analysis in computer models of webs. We observed that the signal thread imposed no biologically relevant time penalty for vibration propagation. However, loss of energy (attenuation) was a cost associated with remote monitoring via a signal thread. The findings have implications for the biological use of vibrations by spiders, including the mechanisms to locate and discriminate between vibration sources. We show that orb-weaver spiders are fascinating examples of organisms that modify their physical environment to shape their information-acquisition strategy. PMID- 29789946 TI - Outcome of arthroscopic SLAP repair using knot-tying-suture anchors compared with knotless-suture anchors in athletes. AB - INTRODUCTION: Arthroscopic repair is one option for the surgical treatment of type II superior labrum tears from anterior to posterior (SLAP) lesions in athletes' shoulders. MATERIALS AND METHODS: Sixty-one of 78 (78.2%) athletes were retrospectively examined after isolated arthroscopic SLAP repair (group 1/G1: 28x knot-tying anchors; group 2/G2: 33 knotless anchors; follow-up 24 months) and compared to two specific, separate matched volunteer athlete control groups (group 3/G3: 28 athletes matched to G1; group 4/G4: 33 athletes matched to G2). The assessment of G1-4 included numerical analogue scales (NASs: 1-15 scales) and the Athletic Shoulder Outcome Scoring System (ASOSS) score, and the Shoulder Sport Activity Score (SSAS). The preinjury status (FU-1), the status before surgery (FU0), and at follow-up (FU1) were assessed. RESULTS: High external rotation at abduction (hER) was significantly worse in G1 than G2 (FU1: G1, 86.6 degrees +/- 7.7 degrees versus = vs G2, 91.1 degrees +/- 10.7 degrees ; p = 0.03). The ASOSS and SSAS revealed significant impairment in G1-2 compared to G3 4 (ASOSS FU1: 83.9 +/- 19.9 G1 vs 94.6 +/- 7.7 G3; p = 0.002 and 80.3 +/- 17.7 G2 vs 91.8 +/- 9.1 G4; p = 0.002; SSAS 5.9 +/- 2.7 G1 vs 6.9 +/- 1.8 G3; p = 0.02 and 6.3 +/- 2.5 G2 vs 7.4 +/- 1.4 G4; p = 0.06), with 17-20% loss on ASOSS and 23 25% deficits on SSAS. The NAS analysis detected for pain (4 +/- 3.5 vs 3.2 +/- 2.6), satisfaction (2 +/- 0.8 vs 1.8 +/- 0.9), reduction of function (4.6 +/- 3.9 vs 3.9 +/- 3.8) and proficiency (9.6 +/- 4.7 vs 10.9 +/- 3.9) similar impairments in G1-2 (p > 0.05) and better results in G3 and G4 (all p < 0.001). CONCLUSIONS: After SLAP repair, athletes showed underestimated impairment of shoulder sport resumption and proficiency with high rates of shoulder sports cessation. The present data favor the knotless fixation technique, because this fixation technique allowed bilaterally equivalent ranges of motions. The uninjured shoulder athletes also showed functional deficits with significant shoulder sport impairments, which must be considered in outcome analysis and for the rehabilitation program. LEVEL OF EVIDENCE: III, retrospective cohort study. PMID- 29789948 TI - The application of neuromuscular electrical stimulation (NMES) in cancer rehabilitation: current prescription, pitfalls, and future directions. AB - The plethora of treatment complications associated with cancer can be offset by regular exercise participation; however, adherence to current guidelines is poor, in particular in those unable or not allowed to participate in voluntary exercise due to their underlying disease. Alternative therapies such as neuromuscular electrical stimulation (NMES) are promising although previous results in cancer survivors have been equivocal. This is likely in response to methodological issues such as inappropriate NMES prescription. Therefore, the aim of this commentary is to propose three key areas which should be addressed to increase NMES effectiveness in cancer rehabilitation; (1) NMES exercise should target both the neuromuscular and cardiovascular systems through low- and high-frequency modalities, (2) technological advancements such as mobile app-based systems should be leveraged to improve at-home monitoring of home-based NMES exercise, and (3) prescription and progression should follow the fundamental principles of exercise to overcome the heterogeneity in daily physiological, functional, and psychological factors faced by survivors. Addressing these three key areas in future studies may help improve NMES exercise effectiveness and accelerate patient rehabilitation. PMID- 29789949 TI - Photobiomodulation therapy in the management of oral mucositis: search for the optimal clinical treatment parameters. AB - This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented. PMID- 29789947 TI - Relationship between brain function (aEEG) and brain structure (MRI) and their predictive value for neurodevelopmental outcome of preterm infants. AB - : To improve the prediction of neurodevelopmental outcome in very preterm infants, this study used the combination of amplitude-integrated electroencephalography (aEEG) within the first 72 h of life and cranial magnetic resonance imaging (MRI) at term equivalent age. A single-center cohort of 38 infants born before 32 weeks of gestation was subjected to both investigations. Structural measurements were performed on MRI. Multiple regression analysis was used to identify independent factors including functional and structural brain measurements associated with outcome at a corrected age of 24 months. aEEG parameters significantly correlated with MRI measurements. Reduced deep gray matter volume was associated with low Burdjalov Score on day 3 (p < 0.0001) and day 1-3 (p = 0.0012). The biparietal width and the transcerebellar diameter were related to Burdjalov Score on day 1 (p = 0.0111; p = 0.0002). The final multiple regression analysis revealed independent predictors of neurodevelopmental outcome: intraventricular hemorrhage (p = 0.0060) and interhemispheric distance (p = 0.0052) for mental developmental index; Burdjalov Score day 1 (p = 0.0201) and interhemispheric distance (p = 0.0142) for psychomotor developmental index. CONCLUSION: Functional aEEG parameters were associated with altered brain maturation on MRI. The combination of aEEG and MRI contributes to the prediction of outcome at 24 months. What is Known: * Prematurity remains a risk factor for impaired neurodevelopment. * aEEG is used to measure brain activity in preterm infants and cranial MRI is performed to identify structural gray and white matter abnormalities with impact on neurodevelopmental outcome. What is New: * aEEG parameters observed within the first 72 h of life were associated with altered deep gray matter volumes, biparietal width, and transcerebellar diameter at term equivalent age. * The combination of aEEG and MRI contributes to the prediction of neurodevelopmental outcome at 2 years of corrected age in very preterm infants. PMID- 29789950 TI - 3D vision and maintenance of stable pneumoperitoneum: a new step in the development of laparoscopic right hepatectomy. AB - BACKGROUND: Although laparoscopic liver resection is widely performed, many technical difficulties remain, such as accurate isolation/division of hepatic vessels in laparoscopic right hepatectomy (LRH). Innovative surgical devices, such as three-dimensional (3D) laparoscopy and optimized carbon dioxide (CO2) insufflation system, may help to overcome technical difficulties in LRH. The purpose of this study was to analyze the efficacy of 3D vision associated with active pneumoperitoneum maintenance in LRH. METHODS: In our prospectively maintained database from 2006, 75 consecutive LRH from May 2011 to June 2017 were included in this study. All LRH were performed with 2D vision and standard CO2 insufflator (2D-LRH group, 45 cases) or 3D vision with optimized CO2 insufflator (3D-LRH group, 30 cases). Preoperative clinical characteristics, surgical data including operation time of separate steps within the procedure, and postoperative complications were compared between the two groups. RESULTS: Clinical and pathological factors were comparable between two groups. Total operative time was significantly shorter in 3D-LRH group than in 2D-LRH (360 vs 390 min, P = 0.029). Right hepatic pedicle dissection time was significantly shorter in 3D-LRH group (101 vs 123 min, P = 0.003). Liver parenchyma transection time was also shorter in 3D-LRH group (138 vs 151 min, P = 0.089), although not significant. There was no significant difference in liver mobilization time, intraoperative bleeding/transfusion, and postoperative complications. CONCLUSIONS: 3D vision with maintenance of pneumoperitoneum facilitates hepatic vascular isolation/division, and may contribute to the development of LRH. PMID- 29789952 TI - Carotid Body Ablation: a New Target to Address Central Autonomic Dysfunction. AB - PURPOSE OF REVIEW: An abnormal heightened carotid body (CB) chemoreflex, which produces autonomic dysfunction and sympathetic overactivation, is the common hallmark of obstructive sleep apnea (OSA), resistant hypertension, systolic heart failure (HF), and cardiometabolic diseases. Accordingly, it has been proposed that the elimination of the CB chemosensory input to the brainstem may reduce the autonomic and cardiorespiratory alterations in sympathetic-associated diseases in humans. RECENT FINDINGS: A growing body of evidence obtained in preclinical animal models support that an enhanced CB discharge produces sympathetic hyperactivity, baroreflex sensitivity and heart rate variability impairment, breathing instability, hypertension, and insulin resistance. The elimination CB chemosensory input reduces the sympathetic hyperactivity, the elevated arterial blood pressure in OSA and hypertensive models, abolishes breathing instability and improves animal survival in HF models, and restores insulin tolerance in metabolic models. These results highlight the role played by the enhanced CB drive in the progression of sympathetic-related diseases and support the proposal that the surgical ablation of the CB is useful to restore the autonomic balance and normal cardiorespiratory function in humans. Accordingly, the CB ablation has been used in pilot human studies as a therapeutic treatment for resistant hypertension and HF-induced sympathetic hyperactivity. In this review, I will discuss the supporting evidence for a crucial contribution of the CB in the central autonomic dysfunction and the pros and cons of the CB ablation as a therapy to revert autonomic overactivation. The CB ablation could be a useful method to reverse the enhanced chemoreflex in HF and severe hypertension, but caution is required before extensive use of bilateral CB ablation, which abolished ventilatory responses to hypoxia and may impair baroreceptor function. PMID- 29789951 TI - Sleep in Children with Congenital Malformations of the Central Nervous System. AB - PURPOSE OF REVIEW: Congenital malformations of the central nervous system may be seen in isolation or in association with syndromes that have multiorgan involvement. Among the potential health challenges these children may face, sleep concerns are frequent and may include chronic insomnia, sleep-related breathing disorders, and circadian rhythm disorders. RECENT FINDINGS: In this review, we describe recent research into sleep disorders affecting children with congenital malformations of the CNS including visual impairment, septo-optic dysplasia, agenesis of the corpus callosum, Aicardi syndrome, Chiari malformation, spina bifida, achondroplasia, Joubert syndrome, fetal alcohol spectrum disorders, and congenital Zika syndrome. In many cases, the sleep disturbance can be directly related to observed anatomical differences in the brain (such as in apnea due to Chiari malformation), but in most syndromes, a complete understanding of the underlying pathophysiology connecting the malformation with sleep problem is still being elucidated. Our review provides a synthesis of available evidence for clinicians who treat this patient population, in whom appropriate diagnosis and management of sleep problems may improve the quality of life for both patient and caregiver. PMID- 29789953 TI - Update on Tick-Borne Bacterial Diseases in Travelers. AB - PURPOSE OF REVIEW: Ticks are the second most important vectors of infectious diseases after mosquitoes worldwide. The growth of international tourism including in rural and remote places increasingly exposes travelers to tick bite. Our aim was to review the main tick-borne infectious diseases reported in travelers in the past 5 years. RECENT FINDINGS: In recent years, tick-borne bacterial diseases have emerged in travelers including spotted fever group (SFG) rickettsioses, borrelioses, and diseases caused by bacteria of the Anaplasmataceae family. African tick-bite fever, due to Rickettsia africae, is the most frequent agent reported in travelers returned from Sub-Saharan areas. Other SFG agents are increasingly reported in travelers, and clinicians should be aware of them. Lyme disease can be misdiagnosed in Southern countries. Organisms causing tick-borne relapsing fever are neglected pathogens worldwide, and reports in travelers have allowed the description of new species. Infections due to Anaplasmataceae bacteria are more rarely described in travelers, but a new species of Neoehrlichia has recently been detected in a traveler. The treatment of these infections relies on doxycycline, and travelers should be informed before the trip about prevention measures against tick bites. PMID- 29789954 TI - Genetics of Movement Disorders and the Practicing Clinician; Who and What to Test for? AB - PURPOSE OF REVIEW: This review aims to provide the basic knowledge on the genetics of hypokinetic and hyperkinetic movement disorders to guide clinicians in the decision of "who and what to test for?" RECENT FINDINGS: In recent years, the identification of various genetic causes of hypokinetic and hyperkinetic movement disorders has had a great impact on a better definition of different clinical syndromes. Indeed, the advent of next-generation sequencing (NGS) techniques has provided an impressive step forward in the easy identification of genetic forms. However, this increased availability of genetic testing has challenges, including the ethical issue of genetic testing in unaffected family members, "commercially" available home testing kits and the increasing number and relevance of "variants of unknown significance." The emergent role of genetic factors has important implications on clinical practice and counseling. As a consequence, it is fundamental that practicing neurologists have a proper knowledge of the genetic background of the diseases and perform an accurate selection of who has to be tested and for which gene mutations. PMID- 29789955 TI - A gate-opening controlled metal-organic framework for selective solid-phase microextraction of aldehydes from exhaled breath of lung cancer patients. AB - A stainless steel fiber was coated with a gate-opening controlled metal-organic framework ZIF-7 via a sol-gel method and applied to the solid-phase microextraction of aldehydes (hexanal, heptanal, octanal, nonanal, decanal) from exhaled breath by lung cancer patients. The effects of temperature and time on the sorption and desorption were optimized. Under optimum condition, the modified fiber displays enrichment factors (typically ranging from 300 to 10,000), low limits of detection (0.61-0.84 MUg L-1), and wide linear ranges of hexanal, heptanal (5-500 MUg L-1) and octanal, nonanal, decanal (10-1000 MUg L-1). The high extraction capability for aldehydes is thought to result from (a) the combined effects of the large surface area and the unique porous structure of the ZIF-7, (b) the hydrophobicity and gate-opening effect of the sorbent, (c) the high selectivity of the window, and (d) the presence of unsaturated metal coordination sites. The coated fiber is thermally stable and can be re-used >150 times. The relative standard deviation (RSD) for six replicate extractions using a single fiber ranged from 1.4-15.3% for intra-day and 2.4-16.1% for inter-day. The fiber-to-fiber reproducibility for three fibers prepared in parallel was in the range of 2.4-12.6% (RSD). The method was applied to the extraction of aldehydes from real samples and to the quantitation by gas chromatography. Recoveries from spiked samples ranged from 84 to 113%. Graphical abstract A metal organic framework ZIF-7 coated stainless steel fiber was prepared via sol-gel method. The self-made fiber was applied in the solid phase microextraction of aldehydes from exhaled breath of lung cancer patients. PMID- 29789957 TI - Thalamic Lesions and Aphasia or Neglect. AB - PURPOSE OF REVIEW: When the thalamus is damaged, not only are there neurological symptoms such as sensory impairment, hemianopia, or motor control disorders, but there are also various neuropsychological symptoms. We discuss the basic anatomy and function of the thalamus followed by a discussion of thalamic aphasia and hemineglect. RECENT FINDINGS: Subcortical lesions in patients with hemineglect involved the anatomical network directly linked to the superior temporal gyrus. Furthermore, the pulvinar, part of the thalamus, may be associated with hemineglect. General linguistic tasks activated the thalami, depending on the difficulty, as well as the frontal and temporal lobes. The thalamus may play a role in language and be involved in the activation of cortical language areas, and in the linguistic integration function via verbal memory and semantic mechanisms. Thalamic lesions are associated with aphasia and hemineglect. It is possible the mechanisms and such neuropsychological may be different depending on the size and site of the thalamic lesion. PMID- 29789956 TI - Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation. AB - PURPOSE OF REVIEW: To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents. RECENT FINDINGS: Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool. Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts. PMID- 29789959 TI - Simulating the unimolecular decomposition pathways of cyclotrimethylnitramine (RDX) : Decomposition pathways of RDX. AB - Based on the three known proposed pathways for the uni-molecular decomposition of RDX, we have formulated the rate equations. A kinetic Monte Carlo code has been developed and used to simulate the uni-molecular decomposition of RDX based on these equations. The KMC simulations allow one to explore each of the decomposition pathways individually and also the three competing pathways at a specified temperature and pressure. The pressure dependence is incorporated using Lindemann's formalism. The code is validated by reproducing the species evolution along each pathway. Amongst the three proposed pathways, the most likely path of RDX decomposition and the time evolution of various molecular species at different ambient temperatures and pressures are obtained. An analytical model has been developed to reproduce the decomposition pathways, which matches the simulation results. PMID- 29789958 TI - Prosthetic Joint Infections: an Update. AB - PURPOSE OF REVIEW: Prosthetic joint infection (PJI) is a rare but serious complication that is frequently misdiagnosed. We aimed to highlight the nuances of PJI diagnosis and antimicrobial therapies and provide clarity in key areas of management. RECENT FINDINGS: Current research in PJI centers on a potential role for diagnostic biomarkers, molecular techniques, and implant sonication to reduce culture-negativity rates. The optimal duration of antimicrobial therapy remains controversial. A high clinical index of suspicion for PJI combined with data from multiple preoperative and intraoperative tests enables timely diagnosis and treatment. Biomarkers, molecular methods, and implant sonication are currently adjunctive to traditional diagnostic techniques. Shorter courses of antimicrobial therapies as well as the role of chronic suppressive therapy need confirmation by randomized controlled trials. Existing practices for preoperative dental prophylaxis and treatment of asymptomatic bacteriuria warrant revision based on evidence arguing against risk for PJI. PMID- 29789960 TI - Cutaneous Manifestations of Infections in Solid Organ Transplant Recipients. AB - PURPOSE OF REVIEW: Post-transplant infections present a formidable challenge to the physician due to their varied presentation. Many of these infections begin by inoculation following skin compromise or disseminate to the skin hematogenously, making cutaneous manifestations of infection an important diagnostic clue in the immunocompromised. Quality research in this field is lacking, and this articles seeks to review the literature and present a guide to physicians in order for them to suspect certain infections by their cutaneous presentation. RECENT FINDINGS: The cutaneous presentation of opportunistic infections in transplant patients is extremely varied. However, as more case reports are published, certain patterns specific to individual organisms are emerging. In addition, early recognition is improving outcomes and systemic antibiotic therapy success. Early and correct recognition of disseminated infection in the immunocompromised host can be aided by close attention to cutaneous findings. This allows early and correct antibiotic therapy and improves outcomes. PMID- 29789961 TI - Illnesses Associated with Freshwater Recreation During International Travel. AB - PURPOSE OF REVIEW: International travel, adventure travel, and eco-tourism are increasing over the past few decades. This review aims to summarize the spectrum of infections associated with recreational freshwater activities and international travel. RECENT FINDINGS: Recreational water activities can be associated with a wide range of infections. Acute febrile illnesses due to leptospirosis and schistosomiasis are not uncommon in travelers following extensive freshwater exposure. Aeromonas and other water-associated pathogens are important to consider in a traveler presenting with a skin and soft tissue infection. Recreational water activities are often associated with diarrheal illnesses, especially in children, and the range of enteric pathogens includes bacterial pathogens such as Escherichia coli O157:H7 and Shigella species and the protozoan parasites Cryptosporidium and Giardia duodenalis. Infections due to free-living amebas though rare can lead to fulminant central nervous system infections. A diverse range of infections may be associated with freshwater exposure, and it is important that these entities are considered in a returning traveler presenting with an acute illness. PMID- 29789963 TI - Experimental arid land afforestation in Central Anatolia, Turkey. AB - The afforestation of arid lands faces many challenges, and perhaps the most important key for success is choosing one or more species that are adapted well for local environmental conditions. We explored species that would be suitable for the steppe region of Central Anatolia. Intensive site preparation included ripping the subsoil (to 80 cm) and plowing the upper soil before planting seedlings of Elaeagnus angustifolia, Robinia pseudoacacia, Fraxinus angustifolia, and Pinus nigra were used as tree species. We also tested the success of several shrub species: Amygdalus orientalis, Calligonum polygonoides, and Spartium junceum. After five growing seasons, E. angustifolia showed the highest survival, with 80% of planted seedlings remaining. For the shrubs, A. orientalis was the most successful species with a 95% survival rate. Broad-leaved trees grew a cumulative average of 34 cm in height in 5 years, whereas P. nigra seedings grew only 9 cm. The greatest height growth occurred in the shrubs, with A. orientalis gaining 40 cm in height in 5 years. Overall, E. angustifolia and A. orientalis appeared best suited for afforestation in these areas. R. pseodoacacia and F. angustifolia may also be used as alternative species. PMID- 29789962 TI - Genome-based identification and analysis of ionotropic receptors in Spodoptera litura. AB - The ability to sense and recognize various classes of compounds is of particular importance for survival and reproduction of insects. Ionotropic receptor (IR), a sub-family of the ionotropic glutamate receptor family, has been identified as one of crucial chemoreceptor super-families, which mediates the sensing of odors and/or tastants, and serves as non-chemosensory functions. Yet, little is known about IR characteristics, evolution, and functions in Lepidoptera. Here, we identify the IR gene repertoire from a destructive polyphagous pest, Spodoptera litura. The exhaustive analyses with genome and transcriptome data lead to the identification of 45 IR genes, comprising 17 antennal IRs (A-IRs), 8 Lepidoptera specific IRs (LS-IRs), and 20 divergent IRs (D-IRs). Phylogenetic analysis reveals that S. litura A-IRs generally retain a strict single copy within each orthologous group, and two lineage expansions are observed in the D-IR sub-family including IR100d-h and 100i-o, likely attributed to gene duplications. Results of gene structure analysis classify the SlitIRs into four types: I (intronless), II (1-3 introns), III (5-9 introns), and IV (10-18 introns). Extensive expression profiles demonstrate that the majority of SlitIRs (28/43) are enriched in adult antennae, and some are detected in gustatory-associated tissues like proboscises and legs as well as non-chemosensory organs like abdomens and reproductive tissues of both sexes. These results indicate that SlitIRs have diverse functional roles in olfaction, taste, and reproduction. Together, our study has complemented the information on chemoreceptor genes in S. litura, and meanwhile allows for target experiments to identify potential IR candidates for the control of this pest. PMID- 29789965 TI - An ultrasonically controlled switching system for power management in implantable devices. AB - In this paper, we present an ultrasonically controlled switching system that can save the battery power for implantable devices by turning the system on and off, on-demand. Ultrasonic control is employed to reduce the device size, increase the penetration depth, and reduce misalignment sensitivity associated with alternative techniques using permanent magnet and RF signal. As a proof-of concept demonstration, a 665 kHz ultrasonic signal is used to activate a piezoelectric receiver which in turn switches a battery-powered RF system on-and off. In-vitro tests show a reliable switching functionality at distances of up to 8 cm while consuming 43.5 nW (14.5 nA current consumption with 3 V power supply) when the system is in off-state, a factor of 10-100 times lower than the sleep mode power consumption of typical RF SoC systems. The dimension of fabricated prototype is 6.3 * 16.7 * 2? mm3 allowing it to be easily incorporated into many existing implantable devices. PMID- 29789967 TI - Amorphous titania modified with boric acid for selective capture of glycoproteins. AB - Amorphous titania was modified with boric acid, and the resulting material was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction and X-ray photoelectron spectrometry. The new material, in contrast to conventional boronate affinity materials containing boronic acid ligands, bears boric acid groups. It is shown to exhibit high specificity for glycoproteins, and this was applied to design a method for solid phase extraction of glycoproteins as shown for ribonuclease B, horse radish peroxidase and ovalbumin. Glycoproteins were captured under slightly alkaline environment and released in acidic solutions. The glycoproteins extracted were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The binding capacities for ribonuclease B, horse radish peroxidase and ovalbumin typically are 9.3, 26.0 and 53.0 mg ? g-1, respectively. The method was successfully applied to the selective enrichment of ovalbumin from egg white. Graphical abstract Schematic presentation of the capture of glycoproteins by amorphous titania modified with boric acid. PMID- 29789966 TI - Behcet's Syndrome and Nervous System Involvement. AB - PURPOSE OF REVIEW: Although Behcet's syndrome (BS) is classified as a rare disease in European countries and the USA, its neurologic involvement "neuro Behcet's syndrome (NBS)" is commonly included in the differential diagnosis of many inflammatory and vascular central nervous system (CNS) disorders. Clinical and neuroimaging findings support two major forms of NBS: parenchymal NBS (p-NBS) and an extra-parenchymal form that presents with cerebral venous sinus thrombosis (CVST). The present review summarizes recent findings on the etiopathogenesis and clinico-radiological features of this disorder as well as its treatment options. RECENT FINDINGS: Recent laboratory and clinical findings include the discovery of antibodies to human and mouse neuro-fibrils showing cross-reactivity with Streptococcus spp. and Mycobacterium tuberculosis heat shock proteins (HSP) in NBS. Diagnostically, two distinct magnetic resonance imaging (MRI) patterns of spinal cord involvement have been observed: (a) "Bagel sign" and (b) "motor neuron" patterns. Therapeutic studies have shown that infliximab effectively prevents further relapses and stabilizes the symptoms of patients experiencing ongoing clinical relapses while being treated with single or multiple immunosuppressant drugs. Primary neurological involvement referred to as NBS. The majority of patients with NBS present with parenchymal involvement that commonly affects the brain stem-diencephalic region. Headache, dysarthria, ataxia, and hemiparesis are the main clinical features of NBS. PMID- 29789964 TI - Caring for Women with Multiple Sclerosis Across the Lifespan. AB - PURPOSE OF REVIEW: Caring for women with multiple sclerosis (MS), whose first symptoms typically begin during the childbearing years, requires a comprehensive approach to management across a range of reproductive exposures, and beyond through menopause. RECENT FINDINGS: This article summarizes what is known about the disease course in women with MS, how it differs from men, and the current state of knowledge regarding effects of reproductive exposures (menarche, childbearing, menopause) on MS-related inflammation and neurodegeneration. Recent findings regarding pregnancy-associated relapses in the treatment era, protective effects of breastfeeding, and care for women during the menopausal transition are reviewed. Then, updated recommendations to guiding women during childbearing including pre-conception counseling, discontinuation of MS therapies, and management of postpartum relapses-are provided. Whenever possible, areas of uncertainty and avenues for future research are highlighted. From childhood through the postreproductive life stages, gender and hormonal exposures appear to shape an individual's risk for MS, as well as the experience of living with MS. PMID- 29789968 TI - Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer's disease by evaluating protein interactions through molecular docking and dynamic simulations. AB - Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer's disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer's disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer's disease by inhibiting the protein tyrosine kinase 2 pathway. PMID- 29789971 TI - Compliance with an Enhanced Recovery After a Surgery Program for Patients Undergoing Gastrectomy for Gastric Carcinoma: A Phase 2 Study. AB - BACKGROUND: Enhanced recovery after surgery (ERAS) programs have gained widespread acceptance in different fields of major surgery. However, most elements of perioperative care in ERAS are based on practices that originated from colorectal surgery. This study investigated compliance with the main elements of ERAS for patients undergoing gastrectomy for gastric carcinoma. METHODS: This phase 2 study enrolled 168 patients undergoing elective gastrectomy for gastric carcinoma. An ERAS program consisting of 18 main elements was implemented, and compliance with each element was evaluated (ClinicalTrials.gov, NCT01653496). RESULTS: Distal gastrectomy was performed for 142 patients (84.5%) and total gastrectomy for 26 patients (10.1%). Laparoscopic surgery was performed for 141 patients (86%). The postoperative morbidity rate was 9.5%, and the mortality rate was 0%. The rates of compliance with the 18 main elements of ERAS ranged from 88.1 to 100%. The lowest compliance rate was observed in the restriction of intravenous fluid element (88.1%). Overall, all ERAS elements were successfully applied for 122 patients (72.6%). In the multivariate analysis, the significant factors that adversely affected compliance with ERAS were surgery during the early study period [odds ratio (OR) 0.39; p = 0.038], open surgery (OR 0.15; p <0.001), and postoperative morbidity (OR 0.16; p = 0.003). CONCLUSIONS: Most elements of ERAS can be successfully applied for patients undergoing gastrectomy for gastric carcinoma. Multimodal collaboration between providers is essential to achieve proper application of ERAS. PMID- 29789969 TI - Identification of risk factors for toxicity in patients with hormone receptor positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study. AB - BACKGROUND: In hormone receptor-positive advanced breast cancer, a progression free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. METHODS: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade >= 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. RESULTS: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade >= 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age >= 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade >= 3 adverse events. Upon multivariate analysis, age >= 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade >= 3 adverse events. CONCLUSIONS: Age (>= 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring. PMID- 29789970 TI - Motile Dendritic Cells Sense and Respond to Substrate Geometry. AB - Dendritic cell (DC) migration is required for efficient presentation of antigen to T cells and the initiation of an adaptive immune response. In spite of its importance, many aspects of DC migration have not been characterized. DCs encounter a variety of environments with different stiffness and geometry, but the effect of these parameters on DC migration has not yet been determined. We addressed this question by comparing DC motility on standard migration surfaces (polydimethylsiloxane (PDMS)-coated coverslips) and micropost array detectors (mPADs). These two surfaces differ in both stiffness and geometry. We found that DC migration was affected by substrate type, with significant increases in speed and significant decreases in persistence time on mPADs made of PDMS as compared to spin-coated PDMS coverslips. To determine whether the geometry or compliance of the post arrays was responsible for these changes in DC migration, we quantified DC motility on mPADs of identical geometry but different stiffness. Migration was indistinguishable on these mPADs, suggesting that DCs are responsive to geometry of ligand presentation and not stiffness. Further, by micropatterning ligands on flat PDMS surfaces in similar geometries to the mPAD arrays, we determined that DCs respond to the geometry of printed ligand. Finally, we used a variety of small molecule inhibitors to identify pathways involved in geometry sensing. We saw a significant role for myosin contractility and alpha5beta1 integrin engagement. We also noted significant reorganization of the actin cytoskeleton into dynamic actin rings when DCs were motile on posts. From these experiments, we conclude that DCs are insensitive to substrate compliance in the range tested but respond to changes in geometry via a mechanism that involves integrin function, myosin contractility, and remodeling of the actin cytoskeleton. As a possible explanation, we postulate a consistent role for filopodial extension and contraction as the driver of DC motility. PMID- 29789973 TI - Chromosomal distribution of soybean retrotransposon SORE-1 suggests its recent preferential insertion into euchromatic regions. AB - Retrotransposons constitute a large portion of plant genomes. The chromosomal distribution of a wide variety of retrotransposons has been analyzed using genome sequencing data in several plants, but the evolutionary profile of transposition has been characterized for a limited number of retrotransposon families. Here, we characterized 96 elements of the SORE-1 family of soybean retrotransposons using genome sequencing data. Insertion time of each SORE-1 element into the genome was estimated on the basis of sequence differences between the 5' and 3' long terminal repeats (LTRs). Combining this estimation with information on the chromosomal location of these elements, we found that the insertion of the existing SORE-1 into gene-rich chromosome arms occurred on average more recently than that into gene-poor pericentromeric regions. In addition, both the number of insertions and the proportion of insertions into chromosome arms profoundly increased after 1 million years ago. Solo LTRs were detected in these regions at a similar frequency, suggesting that elimination of SORE-1 via unequal homologous recombination was unbiased. Taken together, these results suggest the preference of a recent insertion of SORE-1 into chromosome arms comprising euchromatic regions. This notion is contrary to an earlier view deduced from an overall profiling of soybean retrotransposons and suggests that the pattern of chromosomal distribution can be more diverse than previously thought between different families of retrotransposons. PMID- 29789972 TI - Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67. AB - BACKGROUND: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. METHODS: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0-5 and Ki67 6-20%. Cox regression analysis with log rank testing for recurrence and survival was performed. RESULTS: The study enrolled 241 patients (86%) with Ki67 0-5% and 39 patients (14%) with Ki67 6-20%. Recurrence was seen in 34 patients (14%) with Ki67 0-5% after a median period of 34 months and in 16 patients (41%) with Ki67 6-20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0-5% and respectively 55 and 26% for Ki67 6-20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. CONCLUSIONS: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed. PMID- 29789976 TI - Scopulibacillus cellulosilyticus sp. nov., a cellulose-degrading bacterium isolated from tea. AB - A Gram-stain positive, aerobic, non-motile, endospore-forming and rod-shaped strain (THG-NT9T) was isolated from a green tea sample. Growth occurred at 20-45 degrees C (optimum 28-35 degrees C), at pH 6.0-8.0 (optimum 7.0) and at 0-2.0% NaCl (optimum 0%). Based on 16S rRNA gene sequence analysis, the near phylogenetic neighbours of strain THG-NT9T were identified as Scopulibacillus daqui DSM 28236T (98.6%), Scopulibacillus darangshiensis DSM 19377T (97.4%), Pullulanibacillus pueri CGMCC 1.12777T (96.7%) and Pullulanibacillus camelliae CGMCC 1.15371T (96.3%). The DNA G + C content of strain THG-NT9T was determined to be 47.5 mol %. DNA-DNA hybridization values between strain THG-NT9T and S. daqui DSM 28236T, S. darangshiensis DSM 19377T, P. pueri CGMCC 1.12777T, P. camelliae CGMCC 1.15371T and Pullulanibacillus naganoensis DSM 10191T were 41.3 +/- 0.1 (39.4 +/- 0.4% reciprocal analysis), 39.1 +/- 0.1 (37.3 +/- 0.1%), 21.4 +/- 0.7 (20.1 +/- 0.3%), 20.7 +/- 0.1 (20.1 +/- 0.4%) and 12.1 +/- 0.2% (8.3 +/- 0.2%). The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The quinone was identified as MK-7. The major fatty acids were C18:3 omega7c, iso C15:0, iso-C16:0, iso-C17:0 and anteiso-C17:0. The cell wall type was determined to be A1gamma peptidoglycan with meso-diaminopimelic acid as the diagnostic diamino acid plus alanine and glutamic acid and glucose as the cell wall sugar. On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics, and DNA-DNA hybridization data, strain THG-NT9T represents a novel species of the genus Scopulibacillus, for which the name Scopulibacillus cellulosilyticus sp. nov. is proposed. The type strain is THG-NT9T (= KCTC 33918T = CGMCC 1.16305T). PMID- 29789974 TI - A prospective feasibility study applying the ACOSOG Z0011 criteria to Japanese patients with early breast cancer undergoing breast-conserving surgery. AB - BACKGROUND: In patients undergoing breast-conserving surgery and having positive sentinel lymph nodes (SLNs), the ACOSOG Z0011 trial showed equivalent loco regional outcomes for patients receiving SLN dissection (SLND) alone and those receiving axillary lymph node dissection (ALND). We conducted a prospective single-arm study to confirm the applicability of the Z0011 criteria to Japanese patients with breast cancer. METHODS: Patients meeting the Z0011 inclusion criteria and providing consent to receive no additional ALND were prospectively enrolled at the Osaka International Cancer Institute from April 2012 to December 2016. Cumulative incidence of loco-regional recurrence was estimated and compared to that of the Z0011 study. RESULTS: Among a total of 881 patients who underwent breast-conserving surgery, 189 fulfilling the Z0011 criteria were enrolled and eligible for the subsequent analysis. Adjuvant chemotherapy was given to 113 (59.8%) patients, adjuvant hormone therapy to 170 (89.9%), and whole breast irradiation to 183 (96.8%). The frequency of tumors with positive lymphovascular invasion (p < 0.0001) and macrometastases in SLNs (p < 0.0001) were significantly higher in our study than in the Z0011 study. At the median follow-up of 36 months (range 10-64 months), only 2 of 189 patients (1.1%) experienced loco-regional recurrence. The 5-year cumulative rate of loco-regional recurrences was 1.3% (95% CI 0-3.1%), and the 3-year distant DFS rate was 96.8% (95% CI 94.0-99.6%). CONCLUSIONS: Our prospective study showed that it is feasible to apply the Z0011 strategy to Japanese patients with clinically node-negative breast cancer undergoing breast-conserving surgery with planned whole breast irradiation. PMID- 29789979 TI - Model of dissolution in the framework of tissue engineering and drug delivery. AB - Dissolution phenomena are ubiquitously present in biomaterials in many different fields. Despite the advantages of simulation-based design of biomaterials in medical applications, additional efforts are needed to derive reliable models which describe the process of dissolution. A phenomenologically based model, available for simulation of dissolution in biomaterials, is introduced in this paper. The model turns into a set of reaction-diffusion equations implemented in a finite element numerical framework. First, a parametric analysis is conducted in order to explore the role of model parameters on the overall dissolution process. Then, the model is calibrated and validated versus a straightforward but rigorous experimental setup. Results show that the mathematical model macroscopically reproduces the main physicochemical phenomena that take place in the tests, corroborating its usefulness for design of biomaterials in the tissue engineering and drug delivery research areas. PMID- 29789977 TI - Effect of missing data on multitask prediction methods. AB - There has been a growing interest in multitask prediction in chemoinformatics, helped by the increasing use of deep neural networks in this field. This technique is applied to multitarget data sets, where compounds have been tested against different targets, with the aim of developing models to predict a profile of biological activities for a given compound. However, multitarget data sets tend to be sparse; i.e., not all compound-target combinations have experimental values. There has been little research on the effect of missing data on the performance of multitask methods. We have used two complete data sets to simulate sparseness by removing data from the training set. Different models to remove the data were compared. These sparse sets were used to train two different multitask methods, deep neural networks and Macau, which is a Bayesian probabilistic matrix factorization technique. Results from both methods were remarkably similar and showed that the performance decrease because of missing data is at first small before accelerating after large amounts of data are removed. This work provides a first approximation to assess how much data is required to produce good performance in multitask prediction exercises. PMID- 29789975 TI - Exploring potential applications of a novel extracellular polymeric substance synthesizing bacterium (Bacillus licheniformis) isolated from gut contents of earthworm (Metaphire posthuma) in environmental remediation. AB - The aim was to isolate, characterize, and explore potentials of gut bacteria from the earthworm (Metaphire posthuma) and imply these bacteria for remediation of Cu(II) and Zn(II). An extracellular polymeric substance (EPS) producing gut bacteria (Bacillus licheniformis strain KX657843) was isolated and identified based on 16S rRNA sequencing and phylogenetic analysis. The strain showed maximum tolerance of 8 and 6 mM for Cu(II) and Zn(II) respectively. It removed 34.5% of Cu(II) and 54.4% of Zn(II) at 25 mg L-1 after 72 and 96 h incubation respectively. The bacteria possessed a great potential to produce indole acetic acid (38.49 MUg mL-1) at 5 mg mL-1 L-tryptophan following 12 days incubation. The sterilized seeds of mung beans (Vigna radiata) displayed greater germination and growth under bacterium enriched condition. We observed that the bacterial strain phosphate solubilization ability with a maximum of 204.2 mg L-1 in absence of Cu(II) and Zn(II). Endowed with biosurfactant property the bacterium exhibited 24% emulsification index. The bacterium offered significant potential of plant growth promotion, Cu(II) and Zn(II) removal, and as such this study is the first report on EPS producing B. licheniformis KX657843 from earthworm which can be applied as powerful tool in remediation programs of Cu(II) and Zn(II) contaminated sites. PMID- 29789980 TI - Metabolic remodeling of substrate utilization during heart failure progression. AB - Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is "an engine out of fuel" has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled. PMID- 29789978 TI - Diauxic growth of Clostridium acetobutylicum ATCC 824 when grown on mixtures of glucose and cellobiose. AB - Clostridium acetobutylicum, a promising organism for biomass transformation, has the capacity to utilize a wide variety of carbon sources. During pre-treatments of (ligno) cellulose through thermic and/or enzymatic processes, complex mixtures of oligo saccharides with beta 1,4-glycosidic bonds can be produced. In this paper, the capability of C. acetobutylicum to ferment glucose and cellobiose, alone and in mixtures was studied. Kinetic studies indicated that a diauxic growth occurs when both glucose and cellobiose are present in the medium. In mixtures, D-glucose is the preferred substrate even if cells were pre grown with cellobiose as the substrate. After the complete consumption of glucose, the growth kinetics exhibits an adaptation time, of few hours, before to be able to use cellobiose. Because of this diauxic phenomenon, the nature of the carbon source deriving from a cellulose hydrolysis pre-treatment could strongly influence the kinetic performances of a fermentation process with C. acetobutylicum. PMID- 29789981 TI - Research Driven Policy: Is Financial Capacity Related to Dangerousness? AB - Current Veterans administration policy directly links a Veteran's adjudged capacity to manage personal financial resources with their ability to purchase or possess a firearm, pursuant to the regulatory authority of the National Instant Criminal Background Check System (NICS). Preventing Veterans' suicide is a highly laudable public health objective. Effectively utilizing scientific research to "inform" public policy is equally important. The authors should be congratulated for their efforts. However, it is important in utilizing large set population based data, especially social science data, to evaluate policy alternatives that there be substantial face (i.e., clinical) validity. Correlation does not necessarily represent causation. PMID- 29789982 TI - Challenges Associated with the Use of Policy to Identify and Manage Risk for Suicide and Interpersonal Violence Among Veterans and Other Americans. PMID- 29789984 TI - The Role of HIV Stigma in ART Adherence and Quality of Life Among Rural Women Living with HIV in India. AB - HIV stigma continues to be a barrier to physical and mental health among people living with HIV globally, especially in vulnerable populations. We examined how stigma is associated with health outcomes and quality of life among rural women living with HIV in South India (N = 600). Interviewer-administered measures assessed multiple dimensions of stigma, as well as loneliness, social support, ART adherence, time since diagnosis, and quality of life. Internalized stigma and a lack of social support were associated with a lower quality of life, while the association between internalized stigma and adherence was mediated by the use of stigma-avoidant coping strategies, suggesting that keeping one's diagnosis a secret may make it more difficult to take one's medications. These findings suggest that these women constitute a vulnerable population who need additional services to optimize their health and who might benefit from peer support interventions and stigma-reduction programs for family and community members. PMID- 29789983 TI - Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy. AB - In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship. PMID- 29789985 TI - Geographic and Individual Associations with PrEP Stigma: Results from the RADAR Cohort of Diverse Young Men Who have Sex with Men and Transgender Women. AB - Increasing the uptake of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition among at-risk populations, such as young men who have sex with men (YMSM), is of vital importance to slowing the HIV epidemic. Stigma and negative injunctive norms, such as the so called "Truvada Whore" phenomenon, hamper this effort. We examined the prevalence and types of PrEP stigma and injunctive norm beliefs among YMSM and transgender women and associated individual and geospatial factors. A newly created measure of PrEP Stigma and Positive Attitudes was administered to 620 participants in an ongoing longitudinal cohort study. Results indicated lower stigma among White, compared to Black and Latino participants, and among participants not identifying as male. Prior knowledge about PrEP was associated with lower stigma and higher positive attitudes. PrEP stigma had significant geospatial clustering and hotspots were identified in neighborhoods with high HIV incidence and concentration of racial minorities, whereas coldspots were identified in areas with high HIV incidence and low LGBT stigma. These results provide important information about PrEP attitudes and how PrEP stigma differs between individuals and across communities. PMID- 29789987 TI - ISCA2 mutations manifest differentially from DARS2 mutations. PMID- 29789986 TI - Optimal equation for estimation of glomerular filtration rate in autosomal dominant polycystic kidney disease: influence of tolvaptan. AB - BACKGROUND: The reliability of various equations for estimating the GFR in ADPKD patients and the influence of tolvaptan on the resulting estimates have not been examined when GFR is calculated on the basis of inulin clearance. METHODS: We obtained baseline and on-tolvaptan measured GFRs (mGFRs), calculated on the basis of inulin clearance, in 114 ADPKD, and these mGFRs were compared with eGFRs calculated according to four basic equations: the MDRD, CKD-EPI, and JSN-CKDI equations and the Cockcroft-Gault formula, as well as the influence of tolvaptan and of inclusion of cystatin C on accuracy of the results. Accuracy of each of the seven total equations was evaluated on the basis of the percentage of eGFR values within mGFR +/- 30% (P30). RESULTS: mGFRs were distributed throughout CKD stages 1-5. Regardless of the CKD stage, P30s of the MDRD, CKD-EPI, and JSN-CKDI equations did not differ significantly between baseline values and on-tolvaptan values. In CKD 1-2 patients, P30 of the CKD-EPI equation was 100.0%, whether or not the patient was on-tolvaptan. In CKD 3-5 patients, P30s of the MDRD, CKD-EPI, and JSN-CKDI equations were similar. For all four equations, regression coefficients and intercepts did not differ significantly between baseline and on tolvaptan values, but accuracy of the Cockcroft-Gault formula was inferior to that of the other three equations. Incorporation of serum cystatin C reduced accuracy. CONCLUSIONS: The CKD-EPI equation is most reliable, regardless of the severity of CKD. Tolvaptain intake has minimal influence and cystatin C incorporation does not improve accuracy. PMID- 29789988 TI - Growth performance, blood parameters, carcass characteristics and meat quality traits in Potchefstroom Koekoek chickens fed Lippia javanica leaf meal. AB - Lippia javanica leaves may have nutraceutical bioactivity and thus could be a viable alternative to antibiotic growth promoters in poultry diets. To test this hypothesis, a feeding trial was carried out to determine the effects of dietary inclusion of Lippia javanica leaf meal (LJ) on growth performance, blood parameters, carcass characteristics and meat quality of indigenous Potchefstroom Koekoek (PK) chickens. The leaf meal was used to dilute a commercial chicken grower diet at a rate of 25 or 50 g/kg diet. Two additional experimental diets, a positive control (commercial chicken grower diet with antibiotics, CON+) and a negative control (commercial chicken grower diet without antibiotics, CON-), were also formulated. Feed intake and growth performance were measured over a period of 13 weeks before slaughtering for carcass and meat quality measurements. Blood was collected in week 11 to determine haematological and serum biochemical parameters. Diet had no effect on overall FCE but significantly (P < 0.05) affected bilirubin, alanine aminotransferase (ALT), aspartate transaminase (AST), sodium, potassium, cholesterol and magnesium levels in blood. When included at 50 g/kg, LJ increased carcass weight (P < 0.05). Meat from CON- (6.07) and LJ50 (6.08) chickens had a higher pH than from CON+ (5.9) and LJ25 (5.8) chickens. Breast muscle in CON- chickens had higher (P < 0.05) lightness (L*) value (53.2) compared to chickens fed on other diets. It was observed that meat from LJ25 chickens had the highest for redness value (2.3). It was concluded that L. javanica leaf meal can be included up to 50 g/kg in Potchefstroom koekoek chicken diets without causing negative effects on the birds' feed intake, utilisation and weight gain. Diet-induced changes observed in blood parameters and meat quality fell within the expected normal ranges for indigenous chickens. PMID- 29789990 TI - Fatal Pulmonary and Cerebellar Zygomycosis due to Rhizomucor pusillus in a Ringed Seal (Pusa hispida). AB - A 4-year-old captive ringed seal (Pusa hispida) was treated with subcutaneous antibacterial injections for pus exuding wounds in the skin and associated blubber following a bite attack. Three months after the incident, the animal presented nystagmus and died the following day. At necropsy, there was a 25 * 18 * 25 mm well-delineated, opaque nodular mass in the lung, besides the skin ulcers and localized areas of discoloration in the blubber correlating with the bite wound and injection sites. Histopathology of the pulmonary mass demonstrated severe eosinophilic inflammatory infiltration among numerous intralesional fungal hyphae. The hyphae were irregularly branched, broad and aseptate, consistent of zygomycosis. Magnetic resonance imaging was conducted on the head, which was initially frozen intact, revealing diffuse areas of hyperintensity in the cerebellum. Restricted histopathologic examination of the cerebellum showed severe granulomatous inflammation well spread within the neuroparenchyma, associated with abundant intralesional fungal hyphae similar to those appreciated in the pulmonary mass. Molecular analyses of the fungi in the pulmonary and cerebellar tissue identified the etiologic agent in both sites as Rhizomucor pusillus. The likely route of infection is through inhalation of R. pusillus spores or fragmented hyphae from the environment that developed into an initial pulmonary infection, becoming the source of hematogenous dissemination to the cerebellum. The skin and blubber lesions likely contributed to immunosuppression. Zygomycosis is uncommon in pinnipeds, and the present report emphasizes the importance of considering zygomycete dissemination even when the primary focus is highly confined. PMID- 29789989 TI - Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population. AB - Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95 +/- 17.16 pg/ml, controls: 70.55 +/- 15.87 pg/ml, p < 0.001). G allele of 603A>G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p = 0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p = 0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738 2.651) and 4.41 fold (95% CI 1.404-13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients. PMID- 29789991 TI - Asymptomatic Histoplasma Pylephlebitis in an Orthotopic Liver Transplant Recipient: A Case Report and Literature Review. AB - Histoplasma capsulatum is one of the most common pathogenic dimorphic fungi in Thailand. Its usual clinical syndrome is progressive disseminated histoplasmosis, whereas isolated hepatic histoplasmosis is extremely rare. Here, we report the world's first reported case of hepatic histoplasmosis with pylephlebitis in a 45 year-old Thai male who underwent orthotopic liver transplantation due to hepatitis B cirrhosis. Histopathology of the recipient's liver showed infiltration of fungal organisms in portal vein and hepatic granulomas. Serum H. capsulatum antibody was positive, and molecular identification from the liver revealed the DNA of H. capsulatum. PMID- 29789992 TI - Precise and economic FIB/SEM for CLEM: with 2 nm voxels through mitosis. AB - A portfolio is presented documenting economic, high-resolution correlative focused ion beam scanning electron microscopy (FIB/SEM) in routine, comprising: (i) the use of custom-labeled slides and coverslips, (ii) embedding of cells in thin, or ultra-thin resin layers for correlative light and electron microscopy (CLEM) and (iii) the claim to reach the highest resolution possible with FIB/SEM in xyz. Regions of interest (ROIs) defined in light microscope (LM), can be relocated quickly and precisely in SEM. As proof of principle, HeLa cells were investigated in 3D context at all stages of the cell cycle, documenting ultrastructural changes during mitosis: nuclear envelope breakdown and reassembly, Golgi degradation and reconstitution and the formation of the midzone and midbody. PMID- 29789995 TI - You Can't Take Your Baby Home Yet: A Longitudinal Study of Psychological Symptoms in Mothers of Infants Hospitalized in the NICU. AB - Evidence suggests that mothers of infants hospitalized in the Neonatal Intensive Care Unit (NICU) experience elevated rates of psychological symptoms. However, previous studies of this population have been mainly cross-sectional and have focused on very preterm infants. Although moderate- to late-preterm infants generally thrive, the possible psychological toll on their mothers has not yet been sufficiently examined. In the current study, we used a longitudinal design to investigate whether mothers of moderate- to late-preterm infants experience elevated rates of psychological symptoms during the infant's hospitalization in the NICU and 6 months later. Results indicated that these mothers did show elevated depression, anxiety, and PTSD symptoms, and that symptom levels were similar in mothers of moderate- versus late-preterm infants. Mothers of moderate- to late-preterm infants hospitalized in the NICU appeared to experience these symptoms steadily over a 6-month period after giving birth. These findings suggest a need for greater support for these mothers while in the NICU. PMID- 29789994 TI - Performance Evaluation of a Semi-automated Method for [18F]FDG Uptake in Abdominal Visceral Adipose Tissue. AB - PURPOSE: Severity of abdominal obesity and possibly levels of metabolic activity of abdominal visceral adipose tissue (VAT) are associated with an increased risk for cardiovascular disease (CVD). In this context, the purpose of the current study was to evaluate the reproducibility and repeatability of a semi-automated method for assessment of the metabolic activity of VAT using 2-deoxy-2 [18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/x-ray computed tomography (CT). PROCEDURES: Ten patients with lung cancer who underwent two baseline whole-body [18F]FDG PET/low-dose (LD) CT scans within 1 week were included. Abdominal VAT was automatically segmented using CT between levels L1 L5. The initial CT-based segmentation was further optimized using PET data with a standardized uptake value (SUV) threshold approach (range 1.0-2.5) and morphological erosion (range 0-5 pixels). The [18F]FDG uptake in SUV that was measured by the automated method was compared with manual analysis. The reproducibility and repeatability were quantified using intraclass correlation coefficients (ICCs). RESULTS: The metabolic assessment of VAT on [18F]FDG PET/LDCT scans expressed as SUVmean, using an automated method showed high inter and intra observer (all ICCs > 0.99) and overall repeatability (ICC = 0.98). The manual method showed reproducible inter observer (all ICCs > 0.92), but less intra observer (ICC = 0.57) and less overall repeatability (ICC = 0.78) compared with the automated method. CONCLUSIONS: Our proposed semi-automated method provided reproducible and repeatable quantitative analysis of [18F]FDG uptake in VAT. We expect this method to aid future research regarding the role of VAT in development of CVD. PMID- 29789997 TI - Non-Gaussian Methods for Causal Structure Learning. AB - Causal structure learning is one of the most exciting new topics in the fields of machine learning and statistics. In many empirical sciences including prevention science, the causal mechanisms underlying various phenomena need to be studied. Nevertheless, in many cases, classical methods for causal structure learning are not capable of estimating the causal structure of variables. This is because it explicitly or implicitly assumes Gaussianity of data and typically utilizes only the covariance structure. In many applications, however, non-Gaussian data are often obtained, which means that more information may be contained in the data distribution than the covariance matrix is capable of containing. Thus, many new methods have recently been proposed for using the non-Gaussian structure of data and inferring the causal structure of variables. This paper introduces prevention scientists to such causal structure learning methods, particularly those based on the linear, non-Gaussian, acyclic model known as LiNGAM. These non-Gaussian data analysis tools can fully estimate the underlying causal structures of variables under assumptions even in the presence of unobserved common causes. This feature is in contrast to other approaches. A simulated example is also provided. PMID- 29789996 TI - Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism. AB - PURPOSE: Women with hypopituitarism have increased morbidity and mortality, and hypogonadism has been suggested to be a contributing mechanism. The purpose of this study was to investigate the prevalence of central hypogonadism and hypoandrogenism in women with hypopituitarism at a single Swedish center. METHODS: All consecutive women (n = 184) who commenced growth hormone (GH) replacement therapy at Sahlgrenska University Hospital in Gothenburg between 1995 and 2015 were included. In accordance with the Endocrine Society Clinical Practice Guidelines, strict criteria, based on menstrual history combined with laboratory measurements, were used to define central hypogonadism. Hypoandrogenism was defined as subnormal levels of dehydroepiandrosterone sulfate and/or androstenedione. RESULTS: Central hypogonadism was present in 78% of the women, in 75% of those <= 52 years and in 82% of those > 52 years of age. Hypoandrogenism was found in 61% of all the women and in 92% of those with adrenocorticotropic hormone (ACTH) deficiency. The estrogen substitution rate in hypogonadal women <= 52 years was lower than the hormonal substitution rate in the other pituitary hormone axes (74% versus 100%, P < 0.001). The use of estrogen substitution tended to decrease between 2000 and 2016. Few women received androgen treatment. CONCLUSIONS: In this first study of hypogonadism in women with hypopituitarism, using stringent diagnostic criteria for hypogonadism, the prevalence of central hypogonadism and low androgen levels was high and estrogen substitution was insufficient. Further studies are needed to elucidate the importance of hypogonadism and insufficient sex steroid replacement for the increased morbidity in hypopituitary women. PMID- 29789993 TI - The role of the epithelial-to-mesenchymal transition (EMT) in diseases of the salivary glands. AB - The link between inflammatory microenvironment and cancer emerged in the last years as a decisive factor in the induction of the pathological epithelial mesenchymal transition (EMT). The EMT induces changes of cell states converting the epithelial cells to mesenchymal cells when this program is fully executed and EMT has emerged as a central driver of tumor malignancy. Cellular pathways activated by chronic inflammation brought about by chronic infections, by immune mediated diseases, or by dysregulated wound healing at sites of repetitive tissue injury, constitute risk factors or initial cell transformation and for cancer progression. EMT and its intermediate states have recently been identified as crucial inducers of organ fibrosis, inflammation and tumor progression. In this review, we discuss the current state-of-the-art and latest findings regarding the link between EMT, inflammation, fibrosis and cancer, highlighting the most recent data on EMT-dependent tissue fibrosis during chronic inflammatory salivary glands conditions and salivary glands tumors. PMID- 29789999 TI - Assessing the correct inflation of the endotracheal tube cuff: a larger pilot balloon increases the sensitivity of the 'finger-pressure' technique, but it remains poorly reliable in clinical practice. AB - The pilot balloon palpation (or 'finger-pressure') method is still widely used to assess the endotracheal tube cuff inflation, despite consistent evidence of its poor sensitivity in recognizing cuff overinflation. It was recently speculated that this may be related to the lower wall tension (due to the smaller radius) of the pilot balloon as compared with the cuff, according to Laplace's law. To verify this hypothesis and, secondarily, to assess whether the use of a 'large' pilot balloon (identical to the cuff) increases the reliability of this technique, 62 anesthetists (41 experienced anesthesiologists and 21 residents) were asked to estimate the pressure of a cuff inflated to 88 mmHg into a simulated trachea by feeling both a usual and a modified 'large' pilot balloon. A similar test was repeated at 40 mmHg. After palpation of the usual pilot balloon, only 35% of participants (49% of experienced anesthesiologists and 10% of residents) recognized considerable overinflation (88 mmHg), as compared with 87% of participants (95% of experienced anesthesiologists and 71% of residents) after palpation of the 'large' pilot balloon. Moreover, 89% of participants (85% of experienced anesthesiologists and 95% of residents) believed that pressure was higher in the 'large' balloon than in the normal one. However, only 32% of participants (51% of experienced anesthesiologists and none of residents) recognized slight overinflation (40 mmHg) after feeling the 'large' balloon. The pilot balloon size affects the sensitivity of the 'finger-pressure' technique, but it remains poorly reliable with a larger pilot balloon. PMID- 29789998 TI - The expression and role of lncRNA AX800134 in hepatitis B virus-related hepatocellular carcinoma. AB - Chronic infection with hepatitis B virus (HBV) is one of most important risk factors for the development of hepatocellular carcinoma (HCC). Several long non coding RNAs (lncRNAs) have been shown to be involved in the etiology of HBV related HCC. AX800134 is one recently identified lncRNA associated with HCC. In this study, we validated the upregulated expression of AX800134 in HBV-positive HCC compared with HBV-negative HCC. Furthermore, we found that HBV X protein (HBx) directly triggered AX800134 expression in human hepatoma HepG2 cells. Pro inflammatory cytokine TNFalpha also induced AX800134 upregulation in HBx expressing HepG2 cells, which could be reversed by reactive oxygen species (ROS) scavenger pyrrolidine dithiocarbamate (PDTC). Additionally, silencing AX800134 with siRNA interference remarkably inhibited the growth and invasion of HBx expressing HepG2 cells. AX800134 antagonism also enhanced spontaneous apoptosis of HepG2 cells under serum deprivation condition. Therefore, our results indicate that highly expressed AX800134 acts as an oncogenic factor in HCC, and its upregulation is related with the viral product HBx and chronic inflammation. PMID- 29790001 TI - Enhanced Up-Conversion Emission in Al3+ Co-Doped ZnGa2O4:Yb3+,Tm3+ Powder Phosphors. AB - Yb3+-Tm3+ co-doped up-conversion powder phosphors using Zn(AlxGa1-x)2O4 (ZAGO) as the host materials were synthesized via solid-state reaction successfully. In addition, the morphology, structural characterization and up-conversion luminescent properties were all investigated by scanning electron microscope (SEM), x-ray diffraction (XRD) and fluorescence spectrophotometer (F-7000), respectively. Under the excitation of a 980 nm laser, all as-prepared powders can carry out blue emission at about 477 nm (corresponding to 1G4 -> 3H6 transition of Tm3+ ions), and red emission at about 691 nm (attributed to 3F3 -> 3H6 transition of Tm3+ ions). Also, the influence of doping Al3+ ions were investigated. In brief, the doping of Al3+ ions has no effect on the position of emission peak. Howbeit the up-conversion efficiency and intensity of ZAGO:Yb,Tm phosphors are stronger than ZGO:Yb,Tm and ZAO:Yb,Tm phosphors, while the crystallinity is the opposite. More particularly, all as-prepared powder phosphors emit strong luminescence, which is observable by the naked eye, demonstrating the potential applications in luminous paint, luminescent dye, etc. PMID- 29790003 TI - Rationalizing the path to a universal graft recipient. AB - The goal of this essay is to take the reader through the logic that would predict universal graft acceptance. The story begins with what we learned from an experiment performed 65 years ago and develops that information in greater depth. The pathway of the analysis leads to the conclusion that controlling the immune system at the level of the T-helper would be the best way to approach a general solution to the problem of graft acceptance. PMID- 29790002 TI - Superior Visual Search and Crowding Abilities Are Not Characteristic of All Individuals on the Autism Spectrum. AB - Individuals with Autism Spectrum Disorder (ASD) often excel on visual search and crowding tasks; however, inconsistent findings suggest that this 'islet of ability' may not be characteristic of the entire spectrum. We examined whether performance on these tasks changed as a function of motor proficiency in children with varying levels of ASD symptomology. Children with high ASD symptomology outperformed all others on complex visual search tasks, but only if their motor skills were rated at, or above, age expectations. For the visual crowding task, children with high ASD symptomology and superior motor skills exhibited enhanced target discrimination, whereas those with high ASD symptomology but poor motor skills experienced deficits. These findings may resolve some of the discrepancies in the literature. PMID- 29790000 TI - O-GlcNAc cycling in the developing, adult and geriatric brain. AB - Hundreds of proteins in the nervous system are modified by the monosaccharide O GlcNAc. A single protein is often O-GlcNAcylated on several amino acids and the modification of a single site can play a crucial role for the function of the protein. Despite its complexity, only two enzymes add and remove O-GlcNAc from proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Global and local regulation of these enzymes make it possible for O-GlcNAc to coordinate multiple cellular functions at the same time as regulating specific pathways independently from each other. If O-GlcNAcylation is disrupted, metabolic disorder or intellectual disability may ensue, depending on what neurons are affected. O GlcNAc's promise as a clinical target for developing drugs against neurodegenerative diseases has been recognized for many years. Recent literature puts O-GlcNAc in the forefront among mechanisms that can help us better understand how neuronal circuits integrate diverse incoming stimuli such as fluctuations in nutrient supply, metabolic hormones, neuronal activity and cellular stress. Here the functions of O-GlcNAc in the nervous system are reviewed. PMID- 29790005 TI - Howell-Jolly bodies in systemic amyloidosis. PMID- 29790004 TI - Exploring sex-specific differences in the presentation and outcomes of ANCA associated vasculitis: a nationwide registry-based cohort study. AB - PURPOSE: Sex-specific differences in the risk of end-stage renal disease (ESRD) in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) stratified by histological classification have not been previously investigated. METHODS: Patients with biopsy-verified pauci-immune necrotizing GN and positive ANCA serology in the Norwegian Kidney Biopsy Registry between 1991 and 2012 were included. Patients with ESRD during follow-up were identified from the Norwegian Renal Registry. ESRD-free survival stratified by histological classifications was investigated. RESULTS: We analyzed 358 patients, of whom 87 progressed to ESRD during follow-up. Overall ESRD-free survival at 1 and 5 years in the entire cohort was 81 and 71% in males versus 90 and 80% in females, respectively; 94 and 84% in males versus 98 and 98% in females with focal histology, respectively; 85 and 76% in males versus 89 and 77% in females with mixed histology, respectively; 72 and 58% in males versus 90 and 78% in females with crescentic histology, respectively; and 52 and 46% in males versus 60 and 38% in females with sclerotic histology, respectively. Males had an increased risk of ESRD (adjusted hazard ratio, 2.44 [1.56-3.82]; p < 0.001). CONCLUSION: Male sex is associated with increased risk of ESRD across all histological classes of ANCA-GN. PMID- 29790006 TI - Screening Urinalysis in Detection of Chronic Kidney Disease in Children. PMID- 29790007 TI - Sublingual Immunotherapy Decreases Expression of Interleukin-33 in Children with Allergic Rhinitis. AB - OBJECTIVES: To identify the expression of IL-33 during SLIT (Sublingual immunotherapy) in AR (Allergic rhinitis) children. METHODS: Thirty children received house dust mite (HDM) allergen extract for SLIT and thirty children received placebo in this study. Serum and nasal lavage samples of cases and controls were collected at different time points during SLIT. Interleukin (IL)-33 and other cytokines were estimated in these samples by enzyme-linked immuno sorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were prepared and stimulated with rhIL-33 (with or without other stimulators) at different time points during SLIT. RESULTS: The present results showed that both serum and nasal lavage of IL-33 levels decreased significantly after 12 mo treatment and this trend maintained at least until 24 mo. The decreased nasal IL-33 level was positively correlated to local Th2 cytokines and increased IL-10 expression at 2 y post SLIT treatment. In vitro experiments showed that IL-33 promotes IL-4 and IL-5 and inhibits IL-10 expression by peripheral blood mononuclear cells (PBMCs) in AR. CONCLUSIONS: Decreased IL-33 expression during SLIT may contribute to low Th2 response and enhanced Regulatory T cell cytokines expression. Thus, IL-33 maybe an important predictor during SLIT. PMID- 29790008 TI - Methylphenidate Induced Acute Dystonic Reaction. PMID- 29790009 TI - A new model of the spinal locomotor networks of a salamander and its properties. AB - A salamander is an ideal animal for studying the spinal locomotor network mechanism of vertebrates from an evolutionary perspective since it represents the transition from an aquatic to a terrestrial animal. However, little is known about the spinal locomotor network of a salamander. A spinal locomotor network model is a useful tool for exploring the working mechanism of the spinal networks of salamanders. A new spinal locomotor network model for a salamander is built for a three-dimensional (3D) biomechanical model of the salamander using a novel locomotion-controlled neural network model. Based on recent experimental data on the spinal circuitry and observational results of gaits of vertebrates, we assume that different interneuron sets recruited for mediating the frequency of spinal circuits are also related to the generation of different gaits. The spinal locomotor networks of salamanders are divided into low-frequency networks for walking and high-frequency networks for swimming. Additionally, a new topological structure between the body networks and limb networks is built, which only uses the body networks to coordinate the motion of limbs. There are no direct synaptic connections among limb networks. These techniques differ from existing salamander spinal locomotor network models. A simulation is performed and analyzed to validate the properties of the new spinal locomotor networks of salamanders. The simulation results show that the new spinal locomotor networks can generate a forward walking gait, a backward walking gait, a swimming gait, and a turning gait during swimming and walking. These gaits can be switched smoothly by changing external inputs from the brainstem. These properties are consistent with those of a real salamander. However, it is still difficult for the new spinal locomotor networks to generate highly efficient turning during walking, 3D swimming, nonrhythmic movements, and so on. New experimental data are required for further validation. PMID- 29790011 TI - Consecutive occurrence of benign epilepsy with centro-temporal spike and childhood absence epilepsy: true coexistence or atypical evolution? PMID- 29790010 TI - Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films. AB - PURPOSE: Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS: Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium. RESULTS: SEM revealed lamellar structures within the films, which had a thickness ranging 40-240 MUm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60-80% of the total amount of metronidazole was released in 30 min depending on the film formulation. CONCLUSIONS: The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe. PMID- 29790012 TI - Evaluation of a nanocomposite of PEG-curcumin-gold nanoparticles as a near infrared photothermal agent: an in vitro and animal model investigation. AB - Hyperthermia is a promising alternative modality for the conventional cancer treatments. Nanoparticle-mediated photothermal therapy (PTT) has been widely applied for hyperthermia cancer therapy by a near-infrared light irradiation. Some special nanoparticles can convert light energy into heat and destroy the tumor cells. Inspired from the photothermal efficacy of the gold nanoparticles, here we synthesized, characterized, and applied novel photothermal polyethylene glycol-curcumin-gold nanoparticles (PEG-Cur-Au NPs) in cancer PTT. The effect of PEG-Cur-Au NPs upon irradiation by an 808-nm laser on C540 (B16/F10) cell line as well as implanted (bearing) melanoma tumor in inbred C57 mice was investigated. In vitro temperature increment, cell viability evaluation, and histological analyses were performed. The results showed a dose-dependent cytotoxicity of PEG Cur-Au NPs toward C540 (B16/F10) cell line at concentrations >= 25 MUg mL-1 with an IC50 value of 42.7 MUg mL-1 in dark (and with no toxicity for 10 MUg mL-1). On the other hand, 808-nm laser irradiation alone (without using PEG-Cur-Au NPs) for 10 min induced killing effect on the C540 (B16/F10) cell line in a laser power dependent manner at power density > 0.5 W cm-2 (no toxicity for 0.5 W cm-2). However, PPT using PEG-Cur-Au NPs was tremendously observed after laser illumination. Even under laser irradiation at a power density of 0.5 W cm-2 of PEG-Cur-Au NPs of concentrations < 10 MUg mL-1, PTT of the cells was substantial. Histological analyses and volume measurements of the induced tumors in the mice revealed an appropriate control of the tumors upon PTT by PEG-Cur-Au NPs. Combination of PEG-Cur-Au NP administration and 808-nm diode laser irradiation destroyed the melanoma cancer cells in the animal model. PMID- 29790014 TI - Biochemical profile of non-enzymatic stress markers in the plant species "Urginea maritima" in a Mediterranean natural reserve exposed to oxidative stress. AB - Protected areas decrease degrading natural ecosystems due to pollution such as air pollution. In 1981, the inhabitants founded Bentael natural reserve in Byblos, Lebanon, to secure their region against urbanization projects, like the recently constructed road that threatens the biodiversity of the reserve. This study was conducted to determine the oxidative stress resulting from this pollution and that menaces 360 floral species among them a rare species "Urginea maritima." In this research, the biomonitoring approach was experienced to assess the oxidative stress. Biomonitoring possesses has the advantage to be low cost and a constructive method to generate valuable data for further examinations. The studied parameters were air pollutants, ascorbic acid, photosynthetic pigments, leave's pH, relative water content, proline, carbohydrates, and hydrogen peroxide, in three chosen spots, near the pollution source (P1), opposite the latter spot (P2), and in an area relatively far from the source of contamination and which was chosen as the control site (Ctrl). The results showed in P1 detection of air pollutants higher of about 80% than in Ctrl, modifications in stress markers: increased concentration of the reactive oxygen species "hydrogen peroxide," rise in the concentration of the osmoregulator amino acid "proline," and depletion in chlorophyll content, in contrast to an increase in pheophytin. All these findings can be exploited as early diagnosis of air pollution and confirmed the ability to use such biomonitor ("Urginea maritima") as a way to assess the environmental pollution levels and consequently affirm the danger of such landscape activities on natural reserves. PMID- 29790016 TI - Correction to: Abstracts of the 27th Annual Conference of APASL, March 14-18, 2018, New Delhi, India. AB - The aim of this erratum is to correct the sequence of the authors which were listed erroneously in the published version. The correct sequence is mentioned below. PMID- 29790013 TI - Effect of photobiomodulation (670 nm) associated with vitamin A on the inflammatory phase of wound healing. AB - Wound healing is a complex biological process with specific phases. Photobiomodulation (PBM) decreases the inflammatory infiltrate, stimulating fibroblast proliferation and angiogenesis, and therefore, is indicated for wound healing. Vitamin A is used to reverse the inhibitory effects on wound healing and accelerate the healthy granulation tissue. The study aimed to evaluate the effect of topical vitamin A and PBM (GaAlAs) in inflammatory phase of cutaneous wounds. Forty Wistar male rats were separated into four groups: (1) control (CG); (2) laser group (LG) GaAlAs, 670 nm, 30 mW, energy per point of 0.9 J, radiating by 1 point in 30 s; (3) vitamin A group (VitAG); and (4) laser group plus vitamin A (LG + VitAG). Wounds were surgically made by a punch biopsy with 10 mm of diameter on the back of the animals and all treatments were started according to the experiment. The treatments were administered for four consecutive days and biopsy was performed on day 4. We performed both H&E and immunohistochemistry analysis. The results were compared between groups by one-way analysis of variance ANOVA test with post hoc Tukey (p < 0.05). Inflammatory infiltrate increased significantly in LG compared to CG and VitAG (p < 0.05). Regarding angiogenesis, VEGF expression was increased significantly in LG and LG + VitAG groups, p < 0.01. The results indicate that proposed treatments were effective on the healing process improved by LG and LG + VitAG. We show that laser plus vitamin A enhances healing by reducing the wound area and may have potential application for clinical management of cutaneous wounds. PMID- 29790017 TI - Machine learning in the integration of simple variables for identifying patients with myocardial ischemia. AB - BACKGROUND: A significant number of variables are obtained when characterizing patients suspected with myocardial ischemia or at risk of MACE. Guidelines typically use a handful of them to support further workup or therapeutic decisions. However, it is likely that the numerous available predictors maintain intrinsic complex interrelations. Machine learning (ML) offers the possibility to elucidate complex patterns within data to optimize individual patient classification. We evaluated the feasibility and performance of ML in utilizing simple accessible clinical and functional variables for the identification of patients with ischemia or an elevated risk of MACE as determined through quantitative PET myocardial perfusion reserve (MPR). METHODS: 1,234 patients referred to Nitrogen-13 ammonia PET were analyzed. Demographic (4), clinical (8), and functional variables (9) were retrieved and input into a cross-validated ML workflow consisting of feature selection and modeling. Two PET-defined outcome variables were operationalized: (1) any myocardial ischemia (regional MPR < 2.0) and (2) an elevated risk of MACE (global MPR < 2.0). ROC curves were used to evaluate ML performance. RESULTS: 16 features were included for boosted ensemble ML. ML achieved an AUC of 0.72 and 0.71 in identifying patients with myocardial ischemia and with an elevated risk of MACE, respectively. ML performance was superior to logistic regression when the latter used the ESC guidelines risk models variables for both PET-defined labels (P < .001 and P = .01, respectively). CONCLUSIONS: ML is feasible and applicable in the evaluation and utilization of simple and accessible predictors for the identification of patients who will present myocardial ischemia and an elevated risk of MACE in quantitative PET imaging. PMID- 29790018 TI - Forget Evil: Autonomy, the Physician-Patient Relationship, and the Duty to Refer. AB - Aulisio and Arora argue that the moral significance of value imposition explains the moral distinction between traditional conscientious objection and non traditional conscientious objection. The former objects to directly performing actions, whereas the latter objects to indirectly assisting actions on the grounds that indirectly assisting makes the actor morally complicit. Examples of non-traditional conscientious objection include objections to the duty to refer. Typically, we expect physicians who object to a practice to refer, but the non traditional conscientious objector physician refuses to refer. Aulisio and Arora argue that physicians have a duty to refer because refusing to do so violates the patient's values. While we agree with Aulisio and Arora's conclusions, we argue value imposition cannot adequately explain the moral difference between traditional conscientious objection and non-traditional conscientious objection. Treating autonomy as the freedom to live in accordance with one's values, as Aulisio and Arora do, is a departure from traditional liberal conceptions of autonomy and consequently fails to explain the moral difference between the two kinds of objection. We outline how a traditional liberal understanding of autonomy would help in this regard, and we make two additional arguments-one that maintains that non-traditional conscientious objection undermines society's autonomy, and another that maintains that it undermines the physician-patient relationship-to establish why physicians have a duty to refer. PMID- 29790019 TI - Development of a Topical 48-H Release Formulation as an Anti-scarring Treatment for Deep Partial-Thickness Burns. AB - The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20-45% of PF was released in the first 7 h and 70-90% released within 48 h. The rheological properties of the ointment remained stable throughout storage at 25 +/- 2 degrees C/60% RH. Animal studies showed treatments of burn wounds during the inflammatory stage of wound healing with PF ointments at different drug concentrations had no adverse effects on reepithelization. Moreover, 6.5% PF ointment (F3) reduced the expression of pro-inflammatory cytokines IL-12p70 and TNFalpha. This study suggests that hydrocarbon base ointment could be a promising dosage form for topical delivery of PF in treatment of deep partial-thickness burns. PMID- 29790020 TI - Can We Accurately Predict Cost Effectiveness Without Access to Overall Survival Data? The Case Study of Nivolumab in Combination with Ipilimumab for the Treatment of Patients with Advanced Melanoma in England. AB - BACKGROUND: Nivolumab with ipilimumab (the Regimen) is the first immuno-oncology combination treatment to demonstrate long-term clinical benefit for advanced melanoma patients. We evaluated the cost effectiveness of the Regimen in this population, with and without the availability of overall survival (OS) data. METHODS: A partitioned survival model and a Markov state-transition model were developed to estimate the lifetime costs and benefits of the Regimen versus ipilimumab. These models were built with and without the availability of OS data, as only progression-free survival data were available from the head-to-head, phase III trial against ipilimumab at the time of the National Institute for Health and Care Excellence (NICE) submission. Patient utilities and resource use data were sourced from trial data or the literature. RESULTS: Incremental cost effectiveness ratios (ICERs) and absolute costs were similar between the models with and without OS data, but the model with OS data generated more than 1 additional quality-adjusted life-year (QALY) across both treatment arms. In both models, based on list prices, the Regimen was the most cost-effective treatment. CONCLUSIONS: The analyses show that the Regimen is a cost-effective treatment for advanced melanoma patients in England, and methods to overcome the lack of OS can give reasonable estimates of QALYs gained and ICERs. PMID- 29790021 TI - The effect of cholecystectomy on 25-hydroxyvitamin D levels and bone mineral density in postmenopausal women. AB - : Vitamin D deficiency has been reported in patients with gastrointestinal disorders. Little is known on the potentially deleterious effect of cholecystectomy on vitamin D levels and osteoporosis. We found that 25 hydroxyvitamin D levels and bone mineral density were lower in patients with prior cholecystectomy. PURPOSE: The influence of bile salts on vitamin D absorption is well-known, and increased incidence of vitamin D deficiency has been reported in patients with gastrointestinal disorders. Little is known on the potentially deleterious effect of cholecystectomy on vitamin D levels and osteoporosis. Herein, we aimed to investigate the effects of cholecystectomy on vitamin D levels and osteoporosis in postmenopausal women. METHODS: The study group comprised 50 postmenopausal women who had previously undergone cholecystectomy; the control group comprised 50 age-matched postmenopausal women. Serum vitamin D, calcium, and phosphorus levels were determined. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. RESULTS: The study group had significantly higher parathyroid hormone levels (94.4 +/- 45.1 vs. 69.2 +/- 37.5, p < 0.001) but significantly lower 25-hydroxyvitamin D levels (16.3 +/- 7.6 vs. 19.8 +/- 8.7, p = 0.03). Compared with the control group, the BMDs of both the lumbar spine (- 1.5 +/- 1.0 vs. - 0.9 +/- 1.0, p = 0.004) and femur (- 0.5 +/- 0.8 vs. 0.19 +/- 1.1, p = 0.001) were significantly lower in the study group. Body mass index [B = 0.81 (CI 0.67-0.98), p = 0.03] and prior cholecystectomy [B = 7.9 (CI 1.0-71.7), p = 0.04] were independent predictors of osteoporosis. CONCLUSION: In postmenopausal women, prior cholecystectomy is associated with lower serum 25-hydroxyvitamin D levels and BMD. PMID- 29790022 TI - Compliance with Pregnancy Prevention Recommendations for Isotretinoin in Estonia in 2012-2016. AB - BACKGROUND: Isotretinoin is an effective treatment for severe acne; no alternative treatment has an equal therapeutic effect. The teratogenic effects of isotretinoin can be avoided, and numerous recommendations and regulations are in force to minimize the risk of pregnancy during treatment. OBJECTIVES: To describe isotretinoin prescription patterns for women aged 15-45 years, assess the concomitancy of isotretinoin and contraceptive use, and determine the rate of potential isotretinoin-exposed pregnancies in Estonia. METHODS: This retrospective, nationwide, population-based, cohort study derived data from national health insurance databases and included female patients aged 15-45 years in Estonia for whom one or more prescriptions for isotretinoin were dispensed between 2012 and 2016. The main outcome was the proportion of women who used systemic isotretinoin and had a concomitant record of (hormonal or intrauterine) contraception use covering the isotretinoin treatment period when pregnancy is contraindicated. RESULTS: Of the 2792 women aged 15-45 years filling an isotretinoin prescription, 15.7% (95% CI 14.4-17.1) had full and 13.9% (95% CI 12.7-15.3) partial (not covering the whole period during which pregnancy is contraindicated) contraceptive coverage. The risk for potential isotretinoin exposed pregnancy was 3.6 (95% CI 2.0-7.0) per 1000 treated women over the 5-year observation period. The odds for full coverage with effective contraception increased with the age of the patient, with the duration of isotretinoin treatment and over the period of observation. CONCLUSION: Our study adds to the existing literature documenting limited compliance with pregnancy prevention programs for isotretinoin-containing products, and calls for program assessment to identify whether new measures should be taken or whether weaknesses in policy or implementation can be corrected. PMID- 29790023 TI - Atria Depolarization in Rats with Alcoholic Cardiomyopathy. AB - Chronotopography of atrial subepicardium depolarization has been studied in a rat model of alcoholic cardiomyopathy. Formation of independent sources of initial atrial activity has been detected in the right and left atria. These sources induced the formation of several depolarization fronts that propagated autonomously, and this can be regarded as the cause of atrial arrhythmia. PMID- 29790024 TI - Mechanism of Activation of Enteric Nociceptive Neurons via Interaction of TLR4 and TRPV1 Receptors. AB - Evidence obtained by immunohistochemical double labeling and confocal laser scanning microscopy suggests that capsaicin, a ligand of the TRPV1 nociceptive vanilloid receptor, increases the number of TLR4-positive neurons in the rat colon myenteric plexus. In colitis caused by trinitrobenzene sulfonate, an increase in TRPV1 expression was more significant in both plexuses. Specific inhibitor of the TLR4 (C34) pattern-recognition receptor reduces TRPV1 expression in enteric neurons of both intact rats and rats with induced acute colitis. Thus, stimulation of nociceptive neurons by means of direct activation of their receptors of innate immunity (TLR4) is one of the possible mechanisms underlying the visceral pain in bacterial invasion and inflammatory bowel diseases. PMID- 29790025 TI - AMPAR-mediated Interictal Discharges in Neurons of Entorhinal Cortex: Experiment and Model. AB - The mechanisms of interictal discharges (IID) were studied under the conditions of the 4-aminopyridine model of spontaneous epileptiform activity in surviving rat brain slice preparations. Addition of the agents blocking GABA and NMDA receptors failed to inhibit IID generation in the entorhinal cortex. A mathematical model of IID has been developed on the basis of the excitatory neuron interaction mediated by the AMPA receptor. Short-term synaptic depression and slow afterspike-hyperpolarization are the key factors required to terminate a single IID. The IID shape-determining factors have been identified. The experimental and model IID features correspond to each other. PMID- 29790026 TI - Pathogenetic Role of the Stress-induced Release of Glucocorticoid Hormones in the Development of Post-traumatic Stress Disorder: An Experimental Study. AB - In the rat experimental model of posttraumatic stress disorder (PTSD), the level of blood corticosterone was at least eight-fold increased (an overrelease). The use of hypobaric hypoxic preconditioning or short-term inhibition of glucocorticoid synthesis by metyrapone injection prevented development of the experimental PTSD. PMID- 29790027 TI - The Influence of Pre- and Postnatal Factors on Early Behavior Formation. AB - The maternal impact on the early behavioral responses in pups was studied in cross-fostering experiments with the newborn Wistar rats (the primiparous females were fostering the pups born to the females parturiated for the second time and vise versa). The maternal experience had a significant influence on the function development in both pre- and postnatal periods. Specific features of prenatal ontogeny of pups born by experienced females resulted in further, more stable development of the early behavioral responses. In the postnatal period, the maternal experience determined synchronization of the behavioral responses, which promoted the formation of the functional systems important for the newborn survival. PMID- 29790028 TI - Stimulus for Glucagon-Like Peptide 1 Secretion in Rats. AB - Blood concentration of glucagon-like peptide-1 (GLP-1) increased 5 min after per os administration of water, sodium chloride solution, or glucose solution. Changes in blood osmolality or blood glucose level did not stimulate GLP-1 release. A method of short-term increase in the gastric capacity in rats using an inflating balloon attached to the Foley catheter was developed in order to test the hypothesis that excitation of the upper gastrointestinal tract receptors is a primary signal for the GLP-1 secretion during oral intake of the substances. Mechanical gastric distension in rats caused elevation of the blood GLP-1 concentration which was comparable to the effects of oral administration of water, sodium chloride, and glucose solutions. PMID- 29790029 TI - A New Functional Role of Oxytocin: Participation in Osmoregulation. AB - After a water load in rats hyperhydration occurs and the secretion of oxytocin increases by the neurohypophysis. This increases the water diuresis, the water is quickly excreted by the kidney, and the recovery of osmotic homeostasis is accelerated. PMID- 29790030 TI - Molecular Heterogeneity of Lectins in Wheat Seedlings under the Action of Stevioside and Heavy Metals. AB - The effect of the diterpene glycoside stevioside and high concentrations of heavy metals on the molecular heterogeneity of lectins was studied in seedlings of Kazanskaya 560 winter wheat cultivar. Stevioside induced the emergence of a new 45-kDa lectin. Cultivation of wheat seedlings in CdSO4 and ZnSO4 solutions resulted in the emergence of the protein with Mr = 88 kDa. We detected the presence of both lectins in seedlings during combined treatment with stevioside and heavy metals. PMID- 29790031 TI - Effect of Selenium-containing Biocomposites from Medicinal Mushrooms on the Potato Ring Rot Causative Agent. AB - The impact of selenium biocomposites obtained from the medicinal macrobasidiomycetes Ganoderma lucidum, Grifola umbellata, Laetiporus sulphureus, Lentinula edodes, and Pleurotus ostreatus on the viability and biofilm formation capability of the phytopathogenic Gram-positive bacterium Clavibacter michiganensis ssp. sepedonicus (Spieck. et Kotth.) (Cms) was studied. Impairment of bacterial cell viability resulting from their incubation with biocomposites was shown. The decisive role of the composites' selenium component on the biological activity under question was established. The dependence of antimicrobial effect of the selenium-containing specimen on the mushroom systematic position was revealed. The maximal activity was found for the biocomposites based on the extracellular metabolites of L. edodes and G. lucidum. When the biopolymer specimen of fungal origin was added to bacterial suspension, the Cms capability of forming biofilms was found to be distinctly dependent of the biocomposite type, and it was substantially reduced in a number of cases. PMID- 29790032 TI - Is the Center of Origin of Long-tailed Hamster Cricetulus longicaudatus Milne Edwards 1867 (Rodentia, Cricetidae) Located in Tibet? AB - First data on morphological and mitochondrial variation in the long-tailed hamster Cricetulus longicaudatus is presented. In contrast to genetically monomorphic populations of Mongolia and Tuva, the northeastern part of the Qinghai-Tibetian Plateau was found to harbor several divergent mtDNA lineages. This pattern suggests a recent expansion of the long-tailed hamster to the northern part of its recent range, which started from Tibet, presumably, in the late Middle Pleistocene. Several populations from the northern edge of the species range were found to be morphologically but not genetically distinct. The apparent disagreement between genetic and morphological data can be explained by rapid morphological evolution in peripheral isolates. PMID- 29790033 TI - Biomechanical properties of polymer-infiltrated ceramic crowns on one-piece zirconia implants after long-term chewing simulation. AB - BACKGROUND: Implant and superstructure provide a complex system, which has to withstand oral conditions. Concerning the brittleness of many ceramics, fractures are a greatly feared issue. Therefore, polymer-infiltrated ceramic networks (PICNs) were developed. Because of its low Young's modulus and high elastic modulus, the PICN crown on a one-piece zirconia implant might absorb forces to prevent the system from fracturing in order to sustain oral forces. Recommendations for the material of superstructure on zirconia implants are lacking, and only one study investigates PICN crowns on these types of implants. Accordingly, this study aimed to examine PICN crowns on one-piece zirconia implants regarding bond strength and surface wear after long-term chewing simulation (CS). METHODS: Twenty-five hybrid ceramic crowns (Vita Enamic, Vita Zahnfabrik) were produced using computer-aided design/computer-aided manufacturing (CAD/CAM) technology and adhesively bonded (RelyXTM Ultimate, 3M ESPE) to zirconia implants. Twenty of the specimens underwent simultaneous mechanical loading and thermocycling simulating a 5-year clinical situation (SD Mechatronik GmbH). Wear depth and wear volume, based on X-ray micro-computed tomography volume scans (Skyscan 1172-100-50, Bruker) before and after CS, were evaluated. All crowns were removed from the implants using a universal testing machine (Z010, Zwick GmbH&Co.KG). Subsequently, luting agent was light microscopically localized (Stemi 2000-C, Zeiss). With a scanning electron microscope (SEM, PhenomTM G2 pro, Phenom World), the area of abrasion was assessed. RESULTS: 1. After CS, none of the tested crowns were fractured or loosened. 2. The maximum vertical wear after CS was M = 0.31 +/- 0.04 mm (mean +/ standard deviation), and the surface wear was M = 0.74 +/- 0.23 mm3. 3. The pull off tests revealed a 1.8 times higher bond strength of the control group compared to the experimental group (t(23) = 8.69, p < 0.001). 4. Luting agent was mostly located in the crowns, not on the implants. 5. The area of abrasion showed avulsion and a rough surface. CONCLUSIONS: PICN on one-piece zirconia implants showed high bond strength and high wear after CS. PMID- 29790035 TI - Feasibility of intracardiac echocardiography imaging from the left superior pulmonary vein for left atrial appendage occlusion. AB - Intracardiac echocardiography (ICE) is considered an alternative imaging modality for left atrium appendage occlusion (LAAO) to avoid general anesthesia. However, the quality of ICE images obtained from right atrium can be suboptimal compared with transesophageal echocardiography (TEE) imaging. Although placing an ICE probe into left atrium can improve imaging quality, there are limited data regarding procedure outcomes of ICE-guided LAAO versus TEE-guided LAAO. One hundred forty four patients who underwent LAAO with Amplatzer Cardiac Plug, Amulet, or Watchman device were enrolled from two referral institutes. TEE-guided LAAO was performed under general anesthesia or deep sedation (n = 103), and ICE guided LAAO was conducted under local anesthesia (n = 41). An ICE probe was placed into left superior pulmonary vein (LSPV) via transseptal approach. The procedure success and complication rates of the ICE-guided LAAO were comparable with the TEE-guided LAAO (100 vs. 97.1%, p = 1.0; 2.4 vs. 6.8%, p = 0.734, respectively). The procedure time and total radiation dose were significantly lower in ICE-guided group compared with TEE-guided group (58.0 [55.0, 61.0] min vs. 80.0 [58.0, 95.0] min, p < 0.001; 456.0 [359.0, 604.0] mGy vs. 625.0 [439.0, 1502.5] mGy, p < 0.001, respectively). In multivariate analysis, younger age, the last time period of procedure, and local anesthesia were independent factors affecting shorter procedure time. ICE imaging from the LSPV provided optimal views for LAAO procedure with a significant reduction of total procedure time through performing under local anesthesia. This approach can be very useful for LAAO procedure especially in patients who are ineligible for general anesthesia. PMID- 29790034 TI - Left atrial myocardial dysfunction after chronic abuse of anabolic androgenic steroids: a speckle tracking echocardiography analysis. AB - Anabolic-androgenic steroids (AAS) are used by power athletes to improve performance. However, the real effects of the chronic consumption of AAS on cardiovascular structures are subjects of intense debate. To detect by speckle tracking echocardiography (STE) underlying left atrial (LA) dysfunction in athletes abusing AAS and assess possible correlation between LA myocardial function and exercise capacity during cardiopulmonary stress test. 65 top-level competitive bodybuilders were selected (45 males), including 35 athletes misusing AAS for at least 5 years (users), 30 anabolic-free bodybuilders (non-users), compared to 40 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis and bicycle ergometric test were performed to assess LA myocardial function and exercise capacity. Athletes showed increased left ventricular (LV) mass index, wall thickness and stroke volume compared with controls, whereas LV ejection fraction, LV end-diastolic diameter and transmitral Doppler indexes were comparable between the three groups. Conversely, LA volume index, LV and LA strain and LV E/Em were significantly increased in AAS users. By multivariate analyses, LV E/Em (beta = - 0.30, p < 0.01), LA volume index (- 0.42, p < 0.001) and number of weeks of AAS use per year (- 0.54, p < 0.001) emerged as the only independent determinants of LA lateral wall peak STE. In addition, a close association between LA myocardial function and VO2 peak during cardiopulmonary exercise testing was evidenced (p < 0.001), showing a powerful incremental value with respect to clinical and standard echocardiographic data. STE represents a promising technique to assess LA myocardial function in athletes abusing steroids. AAS users showed a more impaired LA deformation, associated with reduced functional capacity during physical effort. PMID- 29790038 TI - Development and Testing of an Addiction Treatment Level of Care Determination Tool. AB - Two studies examined inter-rater reliability and content-related validity of an addiction treatment level of care determination tool currently in use in New York, the LOCADTR 3.0. The studies occurred after tool implementation. In study 1, 139 providers used the LOCADTR 3.0 to determine level of care for four case vignettes. Inter-rater reliability coefficients were calculated. In study 2, 387,338 state records from existing data were analyzed to determine how often providers opted to override the LOCADTR 3.0 level of care determination by choosing an alternative level of care. In study 1, an acceptable inter-rater reliability (IRR = .57-.59) was found. Good indication of content-related validity was also found; participants chose the same level of care the study team chose for each vignette 80% of the time. In study 2, the override option was selected only 10% of the time, further establishing the content validity of the tool. These studies provide evidence for acceptable preliminary reliability and validity of the LOCADTR 3.0. PMID- 29790036 TI - Variability of native T1 values: implication for defining regional myocardial changes using MRI. AB - The aim of the present study was to establish T1 variation (T1v) thresholds for duplicated measurements of regional T1 values in left ventricle (LV) using magnetic resonance imaging (MRI). Eighteen healthy volunteers were recruited to undergo two consecutive cardiac MRI scans using modified Look-Locker Inversion recovery (MOLLI) with two spatial resolutions on different days to repeat T1 measurements on LV. The absolute differences (d) and standard deviations (SDs) of regional T1 values were acquired with the two scans and two readers. T1v threshold (mean difference + 2SD), intra-class correlation coefficient (ICC) and coefficient of variation (CoV) were calculated. T1 mapping using the MOLLI sequence (with multiple spatial resolutions) was successfully performed in all 18 volunteers twice. On a per-slice basis, ICCs for intra-observer, inter-observer, inter-resolution and inter-study T1v were 0.988, 0.899, 0.763 and 0.6. CoVs were 0.72, 2.39, 3.90 and 4.28%. T1v thresholds were 22, 66, 118 and 120 ms. On a per segment basis, ICCs for intra-observer, inter-observer, inter-resolution and inter-study T1v were 0.974, 0.859, 0.711 and 0.594. CoVs were 1.09, 3.36, 4.69 and 5.01%. T1v thresholds were 33, 94, 140 and 144 ms. Those thresholds may be useful for discriminating disease-initiated T1v from random errors of T1 measurements. PMID- 29790039 TI - Intimate Partner Violence and Women with Severe Mental Illnesses: Needs and Challenges from the Perspectives of Behavioral Health and Domestic Violence Service Providers. AB - Women with severe mental illnesses face high rates of violence victimization, yet little is understood about the unique needs and challenges these women present to the domestic violence and behavioral health agencies that serve them. To help address this knowledge gap, focus groups were conducted with 28 staff members from local behavioral health and domestic violence service agencies. Results from this exploratory study suggest that women with severe mental illnesses who experience intimate partner violence face additional challenges that exacerbate behavioral health and domestic violence issues and put these women at greater risk for continued victimization. DV and behavioral health agency staff experience individual-, provider-, and system-level barriers to serving this high risk, high-need population. Recommendations and implications for domestic violence and behavioral health providers are discussed. PMID- 29790037 TI - One-year optical coherence tomography findings in patients with late and very late stent thrombosis treated with intravascular imaging guided percutaneous coronary intervention. AB - Patients with late/very-late stent thrombosis (ST) are at high risk of recurrent ST. The mechanisms of recurrent-ST are largely unknown. The objective is to describe the 1-year optical coherence tomography (OCT) findings of patients suffering from late/very-late ST treated with intravascular imaging guided percutaneous coronary intervention (PCI). All consecutive patients with late/very late ST undergoing intravascular imaging guided PCI were screened to undergo coronary angiography and OCT examination at 1 year. Patients were classified according to the observation of stent malapposition as most contributing cause of the ST. Thirty-four patients were included. Stent malapposition was observed in 17 (50%) and the remaining 17 cases were classified as: neoatherosclerosis (n = 9), underexpansion (n = 3) and unknown mechanism (n = 5). Patients with malapposition had a remarkable reduction of the malapposition volume (from 6.4 to 1.3 mm3; p = 0.02) during the ST procedure, but this was not fully corrected in 13 (76.5%). At 12 months, two patients of the malapposition group presented with uneventful target vessel re-occlusion. Persistent malapposition was observed in nine patients (60.0%). Major coronary evaginations (46.7 vs. 0%; p = 0.001) and uncovered struts (6.3 vs. 1.0%; p < 0.001) were also more frequent in patients with malapposition than without malapposition. None of the patients had thin-cap fibroatheroma neoatherosclerosis. Contributing causes of late/very-late ST are diverse and have different healing patterns at 12 months. Patients with stent malapposition treated with intravascular imaging guided PCI showed poor re healing; but patients with other causes of the ST showed optimal stent healing as assessed by OCT. PMID- 29790040 TI - Building Behavioral Health Homes: Clinician and Staff Perspectives on Creating Integrated Care Teams. AB - Adults with serious mental illness and substance use disorders have elevated risk of mortality and higher healthcare costs compared to the general population. As these disparities have been linked to poor management of co-occurring chronic conditions in primary care, the behavioral health setting may be a preferred setting for routine medical screening and treatment. This qualitative study describes early stages of integrating care teams in emerging medical homes based in mental health and addiction treatment settings. Clinicians and staff from ten agencies engaged in the Behavioral Health Home Learning Collaborative participated in qualitative interviews exploring local definitions of "behavioral health home" and initial barriers and facilitators to integration. Facilitators included clear staff roles, flexible scheduling, and interdisciplinary huddles and staff trainings. Challenges included workforce, limited use of electronic health records, and differing professional cultures. Participants advocated for new workflows and payment structures to accommodate scheduling demands and holistic case management. PMID- 29790041 TI - Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men. AB - : Peripheral quantitative computed tomography (pQCT) provides biomechanical estimates of bone strength. Rural South Indian men have reduced biomechanical indices of bone strength compared to US Caucasian and Afro-Caribbean men. This suggests an underlying higher risk of osteoporotic fractures and greater future fracture burden among the rural South Indian men. INTRODUCTION: Geographical and racial comparisons of bone mineral density (BMD) have largely focused on DXA measures of areal BMD. In contrast, peripheral quantitative computed tomography (pQCT) measures volumetric BMD (vBMD), bone structural geometry and provides estimates of biomechanical strength. To further understand potential geographical and racial differences in skeletal health, we compared pQCT measures among US Caucasian, Afro-Caribbean, and rural South Indian men. METHODS: We studied men aged >= 60 years enrolled in the Mobility and Independent Living among Elders Study (MILES) in rural south India (N = 245), Osteoporotic Fractures in Men Study (MrOS) in the US (N = 1148), and the Tobago Bone Health Study (N = 828). RESULTS: The BMI (kg/m2) of rural South Indian men (21.6) was significantly lower compared to the US Caucasians (28) and Afro-Caribbean men (26.9). Adjusting for age, height, body weight, and grip strength; rural South Indian men compared to US Caucasians had significantly lower trabecular vBMD [- 1.3 to - 1.5 standard deviation (SD)], cortical thickness [- 0.8 to - 1.2 SD]; significantly higher endosteal circumference [0.5 to 0.8 SD]; but similar cortical vBMD. Afro Caribbean men compared to US Caucasians had similar trabecular vBMD but significantly higher cortical vBMD [0.9 to 1.2 SD], SSIp [0.2 to 1.4 SD], and tibial endosteal circumference [1 SD], CONCLUSIONS: In comparison to US Caucasians, rural South Indian men have reduced bone strength (lower trabecular vBMD) and Afro-Caribbean men have greater bone strength (higher cortical vBMD). These results suggest an underlying higher risk of osteoporotic fractures and greater future fracture burden among rural South Indian men. PMID- 29790043 TI - Antimycin A inhibits cytochrome b559-mediated cyclic electron flow within photosystem II. AB - The light reactions of photosynthesis are known to comprise both linear and cyclic electron flow in order to convert light energy into chemical energy in the form of NADPH and ATP. Antimycin A (AA) has been proposed as an inhibitor of ferredoxin-dependent cyclic electron flow around photosystem I (CEF-PSI) in photosynthesis research. However, its precise inhibitory mechanism and target site had not been elucidated yet. Here we show that AA inhibits the cyclic (alternative) electron flow via cytochrome b559 (Cyt b559) within photosystem II (CEF-PSII). When AA was applied to thylakoid membranes isolated from spinach leaves, the high potential form of Cyt b559, which was reduced in the dark, was transformed into the lower potential forms and readily oxidized by molecular oxygen. In the absence of AA, the reduced Cyt b559 was oxidized by P680+ upon light illumination and re-reduced in the dark, mainly by the electron from the QB site on the acceptor side of PSII. In contrast, AA suppressed the oxidation of Cyt b559 and induced its reduction under the illumination. This inhibition of Cyt b559 oxidation by AA enhanced photoinhibition of PSII. Based on the above results, we propose caution regarding the use of AA for evaluating CEF-PSI per se and concurrently propose that AA provides for new insights into, and interpretations of, the physiological importance of Cyt b559, rather than that of CEF-PSI in photosynthetic organisms. PMID- 29790044 TI - Status epilepticus and white matter ischemia complicating dural arteriovenous fistula. PMID- 29790045 TI - Basic red 2 and methyl violet adsorption by date pits: adsorbent characterization, optimization by RSM and CCD, equilibrium and kinetic studies. AB - The potential of raw date pits as a natural, widely available and low-cost agricultural waste has been studied in order to adsorb cationic dyes from an aqueous solution. Date pits were characterized by FTIR, SEM, BET, and XRD analysis. To optimize removal of two industrial dyes, basic red 2 (BR2) and methyl violet (MV), from aqueous solution using date pits, response surface methodology (RSM) is employed. Tests were carried out as per central composite design (CCD) with four input parameters namely contact time, temperature, initial concentration of adsorbate, and pH. Second-order polynomial model better fits experimental data for BR2 and MV and optimum values were then determined. In the optimum conditions, kinetic study was conducted and the pseudo-second-order model was found the best fitted model compared to pseudo-first-order model. Moreover, it was shown that intraparticle diffusion was not the sole controlling step and could be associated with other transfer resistance. On other hand, equilibrium isotherms were obtained for BR2 and MV and their maximum adsorption capacities were 92 and 136 mg g-1 respectively. Two-parameter isotherm models like Langmuir, Temkin, Freundlich, Dubinin-Radushkevich, and Halsay were investigated to fit equilibrium data. Three error functions of residual root mean square error, chi square statistic, and average relative error were used to comfort us in the selected models, which were actually Dubinin-Radushkevich and Langmuir for BR2 and Frendlich, Temkin, and Halsay for MV. PMID- 29790046 TI - Energy consumption habits and human health nexus in Sub-Saharan Africa. AB - This study explores the impact of fossil fuels consumption, solid fuels consumption for cooking purposes, economic growth, and carbon emissions on human health, with a key emphasis on the occurrence of tuberculosis and the high mortality rate in Sub-Saharan Africa. For its practical insights, the study develops a system Generalized Method of Moment (GMM) for a panel of 34 middle- and lower-middle-income countries from 1995 to 2015. The study adopts a flexible methodology to tackle endogeneity in the variables. The robust results report that the use of solid fuels (charcoal, peat, wood, wood pellets, crop residues) for cooking purposes and the consumption of fossil fuels (oil, coal, gas) are significantly increasing the occurrence of tuberculosis. In addition, the results highlight that the consumption of both solid fuels and fossil fuels has adverse affects on life expectancy by increasing the mortality rate in Sub-Saharan African countries. Results report that renewable energy sources like sun, wind, and water (all with potential to prevent households from direct exposure to particulate matters and harmful gases) as well as a rise in economic growth serve as helping factors to control the occurrence of tuberculosis and to decrease the mortality rate. Moreover, the use of renewable energy sources is serving to lessen emissions of carbon dioxide, nitrogen dioxides, and particulate matters, which can ultimately decrease the mortality rate and extend the life expectancy in Sub-Saharan Africa. PMID- 29790042 TI - Orthopaedic regenerative tissue engineering en route to the holy grail: disequilibrium between the demand and the supply in the operating room. AB - Orthopaedic disorders are very frequent, globally found and often partially unresolved despite the substantial advances in science and medicine. Their surgical intervention is multifarious and the most favourable treatment is chosen by the orthopaedic surgeon on a case-by-case basis depending on a number of factors related with the patient and the lesion. Numerous regenerative tissue engineering strategies have been developed and studied extensively in laboratory through in vitro experiments and preclinical in vivo trials with various established animal models, while a small proportion of them reached the operating room. However, based on the available literature, the current strategies have not yet achieved to fully solve the clinical problems. Thus, the gold standards, if existing, remain unchanged in the clinics, notwithstanding the known limitations and drawbacks. Herein, the involvement of regenerative tissue engineering in the clinical orthopaedics is reviewed. The current challenges are indicated and discussed in order to describe the current disequilibrium between the needs and solutions made available in the operating room. Regenerative tissue engineering is a very dynamic field that has a high growth rate and a great openness and ability to incorporate new technologies with passion to edge towards the Holy Grail that is functional tissue regeneration. Thus, the future of clinical solutions making use of regenerative tissue engineering principles for the management of orthopaedic disorders is firmly supported by the clinical need. PMID- 29790049 TI - A simple approach to estimate daily loads of total, refractory, and labile organic carbon from their seasonal loads in a watershed. AB - Loads of naturally occurring total organic carbons (TOC), refractory organic carbon (ROC), and labile organic carbon (LOC) in streams control the availability of nutrients and the solubility and toxicity of contaminants and affect biological activities through absorption of light and complex metals with production of carcinogenic compounds. Although computer models have become increasingly popular in understanding and management of TOC, ROC, and LOC loads in streams, the usefulness of these models hinges on the availability of daily data for model calibration and validation. Unfortunately, these daily data are usually insufficient and/or unavailable for most watersheds due to a variety of reasons, such as budget and time constraints. A simple approach was developed here to calculate daily loads of TOC, ROC, and LOC in streams based on their seasonal loads. We concluded that the predictions from our approach adequately match field measurements based on statistical comparisons between model calculations and field measurements. Our approach demonstrates that an increase in stream discharge results in increased stream TOC, ROC, and LOC concentrations and loads, although high peak discharge did not necessarily result in high peaks of TOC, ROC, and LOC concentrations and loads. The approach developed herein is a useful tool to convert seasonal loads of TOC, ROC, and LOC into daily loads in the absence of measured daily load data. PMID- 29790047 TI - Ascorbic acid inhibits cadmium-induced disruption of the blood-testis barrier by regulating oxidative stress-mediated p38 MAPK pathways. AB - Ascorbic acid (AA), one of the best-known reactive oxygen species (ROS) scavengers, exhibits numerous functions such as antioxidant, anti-cancer, and anti-inflammatory effects. Increasing evidence demonstrates that oxidative stress plays an important role in testicular toxicity. In the present study, we investigated the protective effect of AA against cadmium (Cd)-induced blood testis barrier (BTB) disruption. Sprague-Dawley (SD) rats were divided into four groups: the Cd-treated group received a single dose (s.c.) of 2 mg/kg BW cadmium chloride; the AA antagonism group received an injection of AA at a dose of 400 mg/kg BW (200 mg 24 h prior to Cd treatment and 200 mg 24 h following Cd treatment); and the control groups received an equal volume of saline or an equal dose of AA. As expected, ROS expression was upregulated in the Cd-treated rats, accompanied by an increase in malondialdehyde (MDA). Interestingly, AA suppressed Cd-induced oxidative stress by decreasing the levels of ROS and MDA and increasing the activity of superoxide dismutase (SOD) and catalase (CAT). In addition, AA also reduced BTB disruption by inhibiting TGF-beta3 activation and p38 MAPK phosphorylation. Significant decreases in occludin and claudin-11 expression were observed in the Cd-treated rats, whereas AA administration attenuated this effect. Moreover, testicular histopathology and transmission electron microscopy further demonstrated the protective effects of AA against Cd induced BTB damage. In conclusion, the results of the present study suggest that AA protects BTB destruction via the inhibition of oxidative stress and the TGF beta3/p38 MAPK signalling pathway in the testis of Cd-exposed rats. PMID- 29790048 TI - Analysis of mercury adsorption at the gibbsite-water interface using the CD-MUSIC model. AB - Mercury (Hg), one of the most toxic substances in nature, has long been released during the anthropogenic activity. A correct description of the adsorptive behavior of mercury is important to gain a better insight into its fate and transport in natural mineral surfaces, which will be a prerequisite for the development of surface complexation model for the adsorption processes. In the present study, simulation experiments on macroscopic Hg(II) sorption by gibbsite (alpha-Al(OH)3), a representative aluminum (hydr)oxide mineral, were performed using the charge distribution and multi-site complexation (CD-MUSIC) approach with 1-pK triple plane model (TPM). For this purpose, several data sets which had already been reported in the literature were employed to analyze the effect of pH, ionic strength, and co-exisiting ions (NO3- and Cl-) on the Hg(II) adsorption onto gibbsite. Sequential optimization approach was used to determine the acidity and asymmetric binding constants for electrolyte ions and the affinity constants of the surface species through the model simulation using FITEQLC (a modified code of FITEQL 4.0). The model successfully incorporated the presence of inorganic ligands at the dominant edge (100) face of gibbsite with consistent surface species, which was evidenced by molecular scale analysis. The model was verified with an independent set of Hg(II) adsorption data incorporating carbonate binding species in an open gibbsite-water system. PMID- 29790050 TI - Formulation of oil-in-water emulsions for pesticide applications: impact of surfactant type and concentration on physical stability. AB - Oil-in-water (O/W) emulsions can be utilized as effective pesticide delivery systems in the agricultural industry. In this study, the effects of hydrophile lipophile balance (HLB), concentration, and location of surfactants on the formation and physical stability of O/W emulsions suitable for pesticide applications was investigated using dynamic light scattering and vertical laser profiling. A non-polar pesticide (lambda-cyhalothrin) was used as a model. The pesticide emulsion with the highest stability was obtained using a commercial non ionic surfactant (polyoxyethylene castor oil ether, EL-20) with a required HLB value of 10.5. Emulsion stability increased as the surfactant concentration was increased from 2 to 6%, which was attributed to the formation of smaller oil droplets during emulsification. Emulsions prepared with the surfactant initially in the oil phase were more stable than those prepared with it initially in the aqueous phase. The optimum formulation of the pesticide emulsion was determined as follows: 5% lambda-cyhalothrin (active ingredient) and 6% EL-20 (surfactant) dissolved in 5% S-200 (aromatic hydrocarbon, as oil phase), then deionized water up to 100%, which met the quality indicators set by the FAO standards. The present study is expected to provide useful information to improve the stability of pesticide emulsions for commercial applications. PMID- 29790051 TI - Probabilistic risk-based pollution prevention model for a foundry: a case study of casting. AB - Hazardous air pollutants from industrial activities have long been associated with serious health effects. Traditional health risk assessment uses point estimates of inhalation concentrations based on standard Gaussian diffusion models with steady-state emission rate assumptions. This traditional approach was criticized because it does not account for variability and thus leading to a potential overestimate of the health risk from the batch processes. To overcome this deficiency, a probabilistic risk assessment model is proposed. The foundry industry with processes typically associated with several hazardous air pollutants is identified and iron casting is chosen as a case study to compare risk estimates. Existing data, representing historical proprietary information of the case study, were used to deliver representative risk values and help identify potential replacements or interventions in the manufacturing process. A probability distribution function of emitted concentrations was simulated to model the batch process emissions from mold and core resin binders, a major source of pollution. The same method was applied to exposure factors to feed into the risk model resulting in a probabilistic risk evaluation. Several alternative resin binders in commercial use were examined to offer a risk-based substitute to the resin binder in use. The risk results provided an opportunity to consider newer and environmentally friendlier options. A comparison of the results from this approach and those from the point estimate analysis reveals a gross over estimation of risks. The point estimate risk values were about eight time larger than the mean value and about twice the 95th percentile values of the probabilistic risk approach. The wide range of variability among resin binders associated risk results, close to two orders of magnitude in some cases, presented opportunities to select from a variety of binders with lesser emissions and lower risk. Optimal selection will depend on several pollutants emitted from this process to help address cumulative impacts of multiple pollutants. Investigations are underway for a multi-pollutant strategy including trade-offs, and other quality controls vital to the decision-making. PMID- 29790052 TI - Acid and alkaline solubilization (pH shift) process: a better approach for the utilization of fish processing waste and by-products. AB - Several technologies and methods have been developed over the years to address the environmental pollution and nutritional losses associated with the dumping of fish processing waste and low-cost fish and by-products. Despite the continuous efforts put in this field, none of the developed technologies was successful in addressing the issues due to various technical problems. To solve the problems associated with the fish processing waste and low-value fish and by-products, a process called pH shift/acid and alkaline solubilization process was developed. In this process, proteins are first solubilized using acid and alkali followed by precipitating them at their isoelectric pH to recover functional and stable protein isolates from underutilized fish species and by-products. Many studies were conducted using pH shift process to recover proteins from fish and fish by products and found to be most successful in recovering proteins with increased yields than conventional surimi (three cycle washing) process and with good functional properties. In this paper, problems associated with conventional processing, advantages and principle of pH shift processing, effect of pH shift process on the quality and storage stability of recovered isolates, applications protein isolates, etc. are discussed in detail for better understanding. PMID- 29790053 TI - Innovative sludge pretreatment technology for impurity separation using micromesh. AB - In order to reduce the impacts on sludge treatment facilities caused by impurities such as fibers, hairs, plastic debris, and coarse sand, an innovative primary sludge pretreatment technology, sludge impurity separator (SIS), was proposed in this study. Non-woven micromesh with pore size of 0.40 mm was used to remove the impurities from primary sludge. Results of lab-scale tests showed that impurity concentration, aeration intensity, and channel gap were the key operation parameters, of which the optimized values were below 25 g/L, 0.8 m3/(m2 min), and 2.5 cm, respectively. In the full-scale SIS with treatment capacity of 300 m3/day, over 88% of impurities could be removed from influent and the cleaning cycle of micromesh was more than 16 days. Economic analysis revealed that the average energy consumption was 1.06 kWh/m3 treated sludge and operation cost was 0.6 yuan/m3 treated sludge. PMID- 29790054 TI - Removal of cobalt and lead ions from wastewater samples using an insoluble nanosponge biopolymer composite: adsorption isotherm, kinetic, thermodynamic, and regeneration studies. AB - In this study, an insoluble nanosponge biopolymer composite was synthesized, using a combined process of amidation reaction, cross-linking polymerization, and sol-gel method to obtain a phosphorylated multiwalled carbon nanotube cyclodextrin/silver-doped titania (pMWCNT-betaCD/TiO2-Ag). This work mainly emphasized on the removal of lead (Pb2+) and cobalt (Co2+) metal ions from synthetic and real wastewater samples using the synthesized pMWCNT-betaCD/TiO2-Ag as a biosorbent. The new material was characterized by Fourier transform infrared (FTIR) spectroscopy, zeta potential, Brunauer-Emmett-Teller (BET) method, and scanning electron microscopy (SEM). Adsorption studies for the model pollutants were performed in batch mode. The effect of the solution pH, adsorbent dosage and the presence of competiting ions were investigated. The isotherm, kinetic, thermodynamic, and regeneration studies were also undertaken. The ability of the new material to effectively remove Pb2+ and Co2+ from synthetic wastewater and mine effluent samples was tested. The maximum removal capacities achieved for the removal of Pb2+ and Co2+ from mine effluent sample were 35.86 and 7.812 mg/g, respectively. PMID- 29790055 TI - Polybrominated diphenyl ethers (PBDEs) in core sediments from creek ecosystem: occurrence, geochronology, and source contribution. AB - The levels of 15 polybrominated diphenyl ether (PBDE) congeners in grab sediment and sediment cores from the Thane creek were monitored for their spatial and temporal distribution. Total PBDE (SigmaPBDE) concentrations in grab sediments were ranging from 15.98 to 132.72 ng g-1 dry weight. BDE-209 was the most abundant congener with percentage contribution in the range of 19-35% to total PBDEs. Total PBDE show multimode concentration with depth in sediment, among which mode at a depth of 10 cm is predominant. Results of sediment core also indicates PBDEs were enormously used in last two decades in surrounding area. Sedimentation rate at the creek was also evaluated using Pb210 dating technique. Average percentage contribution of commercial penta-BDE (fP), octa-BDE (fO), and deca-BDE (fD) to the profile found in sediments collected across Thane creek were 24 +/- 5, 5 +/- 1 and 69 +/- 7% (p < 0.001) respectively. Levels of all measured PBDEs in sediment met with guideline values except for the penta-BDE (total, BDE 99 and BDE-100) at few locations. PMID- 29790056 TI - A 10-Year Trend in Statin Use Among Older Adults in Australia: an Analysis Using National Pharmacy Claims Data. AB - BACKGROUND: Statins have become standard of care in the prevention and treatment of atherosclerotic cardiovascular disease. The objective of this study was to examine the trends in statin use among Australians aged >= 65 years for the period 2007-2016. METHODS: Data from the Pharmaceutical Benefits Scheme covering a 10% random sample of the Australian population were analysed. The 1-year prevalence and incidence of statin use were determined for each year, as were the percentage of statin dispensations according to statin type or intensity and the percentage of new users prescribed each statin type or intensity. To describe relative changes, age-sex adjusted rate ratios (RRs) and 95% confidence intervals (CIs) were determined via Poisson regression modelling using 2007 as the reference year. RESULTS: The 1-year prevalence of statin use increased consistently each year from 34.2% in 2007 to 44.1% in 2016 (RR 1.29, 95% CI 1.28 1.31). The 1-year incidence was 68.5 per 1000 in 2007 and 59.0 per 1000 in 2016 (RR 0.87, 95% CI 0.84-0.90). Women were 18% (age-adjusted rate ratio [aRR] 0.82, 95% CI 0.79-0.83) less likely than men to initiate statins across all years. The incidence of statin use was also highest among individuals aged 65-74 years, who were about 15% (sex-adjusted rate ratio [sRR] 1.15, 95% CI 1.13-1.16) and 45% (sRR 1.45, 95% CI 1.44-1.47) more likely to initiate statins than those aged 75 84 and >= 85 years, respectively. Atorvastatin was the most commonly dispensed statin across all years. The proportion of new users dispensed high-intensity statins increased year-on-year from 23.6% in 2007 to 30.5% in 2016 (RR 1.26, 95% CI 1.21-1.31). CONCLUSION: The proportion of older adults in Australia using statins has increased over the last decade, although the incidence has declined. Atorvastatin is the most commonly dispensed statin and the use of high intensity statin has increased. PMID- 29790057 TI - Are youth sport talent identification and development systems necessary and healthy? AB - Talent identification and development systems (TIDS) are commonly used in professional sport to convert youth athletes into sporting stars of the future. Acknowledging that only a few athletes can "make it," the necessity and healthiness of TIDS have recently been questioned based on their increased professionalism, high training, and competition volumes, but limited effectiveness. In this short communication, we suggest that the key issues associated with TIDS are not due to their overall concept, but with how they are designed and implemented. It is recommended that researchers and practitioners determine the worth and value of TIDS by also evaluating the positive health of the athlete rather than solely focusing on performance outcomes. To achieve this, TIDS staff should shape and develop their values, expectations, and day-to-day routines to achieve positive health outcomes focusing on personal development and an athlete-centered culture. In business, this has been termed the concept of "Deliberately Developmental Organisation." TIDS can deploy the factors (e.g., high-quality staff, expert support services, quality facilities, and learning routines) characteristic of such organizations, to concurrently ensure positive impacts and minimize predictable negative outcomes without losing focus on a drive for sporting performance. PMID- 29790058 TI - The synergistic effect of organic acids, phytochemicals and a permeabilizing complex reduces Salmonella Typhimurium 1,4,[5],12:i-shedding in pigs. AB - Salmonella Typhimurium (including S.Typhimurium 1,4,[5],12:i-) and other enteric pathogens cause acute infection in pigs during the weaning stage, often evolving into chronic infections responsible for the introduction of zoonotic bacteria into the slaughterhouse and thus determining carcass contamination. In addition to being zoonotic hazards, these pathogens are responsible for economic losses in affected farms. Traditionally, antibiotic treatments have been largely administered in order to reduce the infection burden but it favored, as a direct consequence, an increase in the number of multi-drug resistance strains. In order to overcome antibiotic-resistance concerns, new alternative control strategies should be developed. In this context, a blend of organic acids, phytochemicals and a permeabilizing complex, administered in feed (Group A - 459 piglets) or water (Group B - 458 piglets), was tested in field conditions for its capability of reducing Salmonella-infection in weaned piglets of an endemic farm. Data recorded were compared to results of a control group (Group C - 456 piglets). Zootechnical parameters were recorded in all animals, while microbiological, serological and PCR analyses were conducted in 15 piglets for each group. Results demonstrated that additive administered in feed improved animal weight gain (better average daily gain [A.D.G.] and increment), and rapidly reduced Salmonella-shedding in feces. Administration of additive in feed gave better results than in water. PMID- 29790059 TI - Characteristics of distribution of Mycobacterium tuberculosis lineages in China. AB - The genotyping methods of Mycobacterium tuberculosis would dramatically improve our understanding of the molecular epidemiology of tuberculosis. 3,929 isolates, from a National Survey of Drug-Resistant Tuberculosis in 2007 in China, were successfully genotyped by large sequence polymorphisms and 15 loci variable number tandem repeats. We found that 2,905 (2,905/3,929, 73.9%) cases belonged to Lineage 2, dominated in the east and central regions, 975 cases (975/3,929, 24.8%) were Lineage 4, highly prevailed in the west regions, and 36 and 13 cases were Lineage 3 and Lineage 1, respectively. We also explored the associations between lineages (Lineage 2 vs. Lineage 4) and clinical characteristics by logistic regression. For Lineage 2, the risk factors were Han-ethnicity population and fever. However, for Lineage 4, they were occupation (farmer), and degree of education (non-literate). Fully understanding of the distribution of Mycobacterium tuberculosis lineage and its risk factors would play a critical role in tuberculosis prevention, control, and treatment. PMID- 29790060 TI - Protect chromosomes from end-to-end fusion during meiotic bouquet. PMID- 29790062 TI - Analysis of Pulse Signals Based on Array Pulse Volume. AB - OBJECTIVE: To collect and analyze multi-dimensional pulse diagram features with the array sensor of a pressure profile system (PPS) and study the characteristic parameters of the new multi-dimensional pulse diagram by pulse diagram analysis technology. METHODS: The pulse signals at the Guan position of left wrist were acquired from 105 volunteers at the Shanghai University of Traditional Chinese Medicine. We obtained the pulse data using an array sensor with 3*4 channels. Three dimensional pulse diagrams were constructed for the validated pulse data, and the array pulse volume (APV) parameter was computed by a linear interpolation algorithm. The APV differences among normal pulse (NP), wiry pulse (WP) and slippery pulse (SP) were analyzed using one-way analysis of variance. The coefficients of variation (CV) were calculated for WP, SP and NP. RESULTS: The APV difference between WP and NP in the 105 volunteers was statistically significant (6.26+/-0.28 vs. 6.04+/-0.36, P=0.048), as well as the difference between WP and SP (6.26+/-0.28 vs. 6.07+/-0.46, P=0.049). However, no statistically significant difference was found between NP and SP (P=0.75). WP showed a similar CV (4.47%) to those of NP (5.96%) and SP (7.58%). CONCLUSION: The new parameter APV could differentiate between NP or SP and WP. Accordingly, APV could be considered an useful parameter for the analysis of array pulse diagrams in Chinese medicine. PMID- 29790061 TI - Acute bleeding obstruction pancreatitis after Roux-en-Y anastomosis in total gastrectomy: a single center experience. AB - Anastomotic intraluminal bleeding is a well-known complication after total gastrectomy. Nevertheless, few data are published on acute bleeding obstruction pancreatitis (BOP) due to a bleeding from the jejunojejunostomy (JJ). In this paper we describe our experience. A total of 140 gastrectomies for EGJ cancer were performed in our Institute from January 2012 to January 2017. All reconstructions were performed with a Roux-en-Y anastomosis: a mechanical end-to side esophago-jejunostomy and a mechanical end-to-side JJ. Three patients suffered from a bleeding at the JJ with a consequent BOP. We analyzed the time of diagnosis, the treatment and the outcomes. The three patients presented anemia at the laboratory findings on postoperative day (POD) 1. In patient I laboratory findings of acute pancreatitis were found in POD 2. CT scan was performed and showed signs of BOP. Endoscopic treatment was tried without success. Therefore, patient underwent surgery: JJ take down, bleeding control and anastomosis rebuild were performed. In spite of this the patient died of MOF in POD 4. Patient II had a persistent anemia treated with blood transfusions until POD 3, when laboratory tests showed increased lipase and bilirubin levels. Patient was successfully treated with endoscopy but several blood transfusions and a prolonged recovery were necessary. Patient III had laboratory findings of acute pancreatitis on POD 1. Immediate surgery was performed and patient was discharged on POD 9 without sequelae. BOP is a rare but deadly complication after Roux-en-Y anastomosis. An early diagnosis and an aggressive treatment seem to improve the outcome. PMID- 29790063 TI - In Vitro and In Vivo Evaluation of Antitumor Activity of Ligustrum robustum, A Chinese Herbal Tea. AB - OBJECTIVE: To examine the effect of the aqueous extract of Ligustrum robustum on tumor growth in vitro and in vivo and explore the possible molecular mechanisms. METHODS: In in vitro study, cell viabilities of human cervical carcinoma cells (HeLa), human breast cancer cells (MCF-7), human prostate cancer cells (PC-3), human hepatoma cells (7721) and human colon carcinoma cells (SW480) were evaluated with cell counting kit-8. For L. robustum-treated Hela cells, early or late apoptosis were evaluated by annexin V/PI staining. Mitochondrial membrane potential was measured by staining cells with JC-1. Apoptosis was monitored by nuclear morphology based on chromatin condensation and fragmentation by 4',6 diamidino-2-phenylinole (DAPI) staining. Caspase-3 and -8 activity levels were measured by a colorimetric assay. In vivo, to evaluate the possible mechanism of L. robustum-mediated antitumor effect, nude mouse xenograft study was also conducted. RESULTS: In in vitro study, L. robustum was found to be toxic to HeLa, MCF-7, PC-3, 7721, SW480, with an half maximal inhibitory concentration value of 2-5 mg/mL (P<0.05). Moreover, externalization of phosphatidylserine, loss of mitochondrial membrane potential, DNA fragmentation and activation of caspase-3 and -8 were detected in L. robustum-treated Hela cells. Using a nude mouse model bearing Hela xenografts, we found that L. robustum reduced tumor volume and tumor weight (P<0.05), but had no effect on body weight and histological damage of important organs. Intraperitoneal injection of L. robustum caused a significant reduction in serum aspartate transaminase and alanine transaminase levels (P<0.05). Furthermore, cleaved caspase-3-positive and terminal nucleotidyl transferase-mediated nick end labeling (TUNEL)-positive cells were observed in L. robustum-treated tumor tissues. CONCLUSIONS: L. robustum inhibits tumor cell growth both in vitro and in vivo by inducing apoptosis in a caspase-dependent way without apparent hepatic toxicity and histological damage, which may offer partial scientific support for the ethnopharmacological claims of L. robustum as a herbal tea for its antitumor activity. PMID- 29790065 TI - Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-kappa B and MAPK Pathways. AB - OBJECTIVE: To investigate the anti-neuroinflammation effect of extract of Fructus Schisandrae chinensis (EFSC) on lipopolysaccharide (LPS)-induced BV-2 cells and the possible involved mechanisms. METHODS: Primary cortical neurons were isolated from embryonic (E17-18) cortices of Institute of Cancer Research (ICR) mouse fetuses. Primary microglia and astroglia were isolated from the frontal cortices of newborn ICR mouse. Different cells were cultured in specific culture medium. Cells were divided into 5 groups: control group, LPS group (treated with 1 MUg/mL LPS only) and EFSC groups (treated with 1 MUg/mL LPS and 100, 200 or 400 mg/mL EFSC, respectively). The effect of EFSC on cells viability was tested by methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay. EFSC mediated inhibition of LPS-induced production of pro-inflammatory mediators, such as nitrite oxide (NO) and interleukin-6 (IL-6) were quantified and neuron protection effect against microglia-mediated inflammation injury was tested by hoechst 33258 apoptosis assay and crystal violet staining assay. The expression of pro-inflammatory marker proteins was evaluated by Western blot analysis or immunofluorescence. RESULTS: EFSC (200 and 400 mg/mL) reduced NO, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression in LPS induced BV-2 cells (P<0.01 or P<0.05). EFSC (200 and 400 mg/mL) reduced the expression of NO in LPS-induced primary microglia and astroglia (P<0.01). In addition, EFSC alleviated cell apoptosis and inflammation injury in neurons exposed to microglia-conditioned medium (P<0.01). The mechanistic studies indicated EFSC could suppress nuclear factor (NF)-kappa B phosphorylation and its nuclear translocation (P<0.01). The anti-inflammatory effect of EFSC occurred through suppressed activation of mitogen-activated protein kinase (MAPK) pathway (P<0.01 or P<0.05). CONCLUSION: EFSC acted as an anti-inflammatory agent in LPS induced glia cells. These effects might be realized through blocking of NF-kappa B activity and inhibition of MAPK signaling pathways. PMID- 29790064 TI - Cohort Study on Prognosis of Patients with Metastatic Colorectal Cancer Treated with Integrated Chinese and Western Medicine. AB - OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine (IM) in the treatment of metastatic colorectal cancer (mCRC) in a cohort study. METHODS: The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of Chinese medicine for ? 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the IM cohort (Group A, 110 patients). Patients who did not meet this exposure factor were assigned to the Western medicine cohort (Group B, 225 patients). The overall survival (OS), progression-free survival (PFS), and 1st year, 2nd year, and 3rd year survival in the two cohorts were compared. RESULTS: The median OS in Group A and B were 18 months [95% confidence interval (CI) 15-21] and 16 months (95% CI 14-18), respectively, and the median PFS in Group A and B were 6 months (95% CI 4 7) and 5 months (95% CI 4-6), respectively. No statistically significant differences were observed between the groups (P=0.186, P=0.223). Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, patients with lesions in the right half of the colon, and those who received first-line treatment (P<0.05). In the subgroup of elderly patients (age>65 years), the OS in Group A was longer than that in Group B (P<0.05). CONCLUSION: IM could prolong the survival of patients with mCRC. (Registry No. ChiCTR-IOR-17010497). PMID- 29790066 TI - Treatment and outcome of thrombosed aneurysms of the middle cerebral artery: institutional experience and a systematic review. AB - Thrombosed aneurysms of the middle cerebral artery (MCA) usually show large dimension and complex morphology with neck sclerosis and perforating vessels originating from the sac. Only limited experiences from case reports or small mixed series including thrombosed aneurysms in different locations are available in literature. To systematically review all the pertinent literature, a comprehensive literature review with the search terms "MCA, aneurysm, and thrombosis" and a pooled analysis including our institutional series were performed. We evaluated demographics, ruptured status, aneurysm morphology, topography and size, thrombosis extension, treatment, complications, final occlusion rate, and clinical outcome at follow-up. Data were individually extracted for each patient and included in a pool for the statistical analysis. Forty-two articles published between 1992 and 2016 were selected, including a total of 115 patients. Most of thrombosed aneurysms were saccular (67.6%), large or giant (86.7%), and located at the MCA bifurcation (67.3%). The treatment of choice was surgery in more than 80% of cases compared with the endovascular techniques, though the overall percentage of complications reported in the two groups was similar and around 20% of cases. Clinical outcome was favorable in more than 85% of patients after treatment. This is the first systematic review focusing on treatment and outcome of thrombosed MCA aneurysms. Our data depict their main angioarchictectural and clinical characteristics, proving the feasibility of their treatment with good prognosis in a high percentage of patients. However, complication and mortality rates of about 20 and 3.5%, respectively, are not negligible. PMID- 29790068 TI - Neuritin Attenuates Neuronal Apoptosis Mediated by Endoplasmic Reticulum Stress In Vitro. AB - Neuritin is an extracellular glycophosphatidylinositol-linked protein that promotes neuronal survival, differentiation, function, and repair, but the exact mechanism of this neuroprotective effect remains unclear. Meanwhile, endoplasmic reticulum stress (ERS) induced apoptosis is attracting increased attention. In this work, we hypothesized that neuritin inhibited ERS to protect cortical neurons. To check this hypothesis, we exposed primary cultured cortical neurons to oxygen and glucose deprivation (OGD) for 45 min followed by reperfusion (R) to activate ERS. We then performed resuscitation for 6, 12, 24, and 48 h. ERS related factors such as glucose-regulated protein 78 (GRP78), caspase-12 and CHOP were detected by Western blotting and quantitative real-time polymerase chain reaction assay. Apoptosis was assessed by Annexin V binding and propidium iodide staining. Ultrastructural changes of endoplasmic reticulum were observed under a transmission electron microscope. Results showed that GRP78 expression significantly increased at 12, 24, and 48 h and peaked at 24 h. Caspase-12 and CHOP expression significantly increased in a time-dependent manner at 12, 24, and 48 h. GRP78, caspase-12 and CHOP expression as well as apoptosis rate of primary cultured neurons and the ultrastructural changes of endoplasmic reticulum in the OGD/R + neuritin group significantly improved compared with the OGD/R group. In conclusion, the neuroprotection function of neuritin may be involved in ERS pathways. PMID- 29790069 TI - Antidepressant Effects of the Ginsenoside Metabolite Compound K, Assessed by Behavioral Despair Test and Chronic Unpredictable Mild Stress Model. AB - Depression is a major social and health problem worldwide. Compound K (CK), an intestinal metabolite of panaxadiol ginsenosides, has been demonstrated to possess significant pharmacological effects on the central nervous system (CNS). Here, we set up this study to investigate the antidepressant effect of CK, and to explore the potential mechanisms underlying this activity. The behavioral despair model and chronic unpredictable mild stress (CUMS) model were established in mice or rats, respectively. Forced swimming test (FST), tail suspension test (TST) and locomotor activity were performed in mice, while the open-field test, food consumption and sucrose preference were assessed in rats. To investigate the underlying mechanism, the levels of endogenous noradrenaline, dopamine (DA), 5 hydroxytryptamine (5-HT) and their metabolites in the prefrontal cortex (PFC) and hippocampus were detected by HPLC coupled with electron detector. The dopamine degradation enzyme (COMT and MAO) expression was measured by western blot. The BDNF and NGF expression were investigated by immunohistochemical staining analysis. The results showed CK (10, 30 mg/kg) intragastric administration for 14 days significantly shorten the immobility time in FST and TST, which could be partially reversed by a D1 receptor antagonist Sch23390. For CUMS rats, CK alleviated the depressant-like behaviors, including decreased food consumption, spontaneous locomotor activity and lower sucrose preference, while WAY-100635, a 5-HT1A receptor antagonist, could attenuate this effect. In addition, CK increased the levels of 5-HT, DA and their metabolites in the PFC and hippocampus of CUMS rats, and could reverse overexpression of MAOB in PFC and hippocampus. CK also increased the GSH and GPx activity in the hippocampus and PFC. The IHC results revealed the BDNF and NGF expression were increased in CK-treated rats. The obtained results indicate that CK exhibits antidepressant effects in rodents, which may be due to the regulation of monoamine neurotransmitter concentration, enhancement of antioxidant capacity, as well as increase of neurotrophin expression in the CNS. PMID- 29790067 TI - Receptor for Advanced Glycation End-Products (RAGE) Blockade Do Damage to Neuronal Survival via Disrupting Wnt/beta-Catenin Signaling in Spinal Cord Injury. AB - Wnt signaling are recognized key factors in neuronal development, cell proliferation and axonal guidance. However, RAGE effect on wnt signaling after spinal cord injury (SCI) are poorly understood. Our study aims to explore RAGE blockade effect on wnt signaling after SCI. We constructed Allen SCI model and micro-injected with RAGE neutralizing antibody or IgG after injury. We determined beta-catenin, wnt3a and its receptor frizzled-5 via Western blot. We determined beta-catenin/NeuN expression at 2 weeks after SCI via immunofluorescence (IF). We found that beta-catenin, wnt3a and wnt receptor frizzled5 expression were activated after SCI at 3 days after injury. However, RAGE blockade inhibit beta catenin, wnt3a and frizzled5 expression. We found that beta-catenin accumulation in NeuN cells were activated after SCI via IF, however, RAGE blockade reduced beta-catenin and NeuN positive cells. RAGE blockade attenuated number of survived neurons and decreased area of spared white matter around the epicenter. RAGE signaling may involved in disrupting wnt signaling to aids neuronal recovery after SCI. PMID- 29790070 TI - Genotyping single-sperm cells by universal MARSALA enables the acquisition of linkage information for combined pre-implantation genetic diagnosis and genome screening. AB - PURPOSE: This paper aims to investigate the feasibility of performing pre implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) simultaneously by a universal strategy without the requirement of genotyping relevant affected family members or lengthy preliminary work on linkage analysis. METHODS: By utilizing a universal Mutated Allele Revealed by Sequencing with Aneuploidy and Linkage Analyses (MARSALA) strategy based on low depth whole genome sequencing (~3x), not involving specific primers' design nor the enrichment of SNP markers for haplotype construction. Single-sperm cells and trephectoderm cells from in vitro fertilized embryos from a couple carrying HBB mutations were genotyped. Haplotypes of paternal alleles were constructed and investigated in embryos, and the chromosome copy number profiles were simultaneously analyzed. RESULTS: The universal MARSALA strategy allows the selection of a euploid embryo free of disease mutations for in uterus transfer and successful pregnancy. A follow-up amniocentesis was performed at 17 weeks of gestation to confirm the PGD/PGS results. CONCLUSION: We present the first successful PGD procedure based on genotyping multiple single-sperm cells to obtain SNP linkage information. Our improved PGD/PGS procedure does not require genotyping the proband or relevant family members and therefore can be applicable to a wider population of patients when conducting PGD for monogenic disorders. PMID- 29790071 TI - Impact of polar body biopsy on embryo morphokinetics-back to the roots in preimplantation genetic testing? AB - PURPOSE: Polar body biopsy (PBB) is a common technique in preimplantation genetic testing (PGT) to assess the chromosomal status of the oocyte. Numerous studies have been implemented to investigate the impact of biopsies on embryo development; however, information on embryo morphokinetics is still lacking. Hence, we investigated the impact of PBB on morphokinetic parameters in early embryo development. METHODS: Four hundred four embryos (202 PBB, 202 control) were retrospectively analyzed. Patients were stimulated with a gonadotropin releasing hormone antagonist ovarian hyperstimulation protocol. After fertilization check, embryos were incubated in a time-lapse incubator. The groups were matched for maternal age at time of oocyte retrieval. RESULTS: Mean group times for reaching specific developmental time points showed no significant difference comparing embryos with PBB conducted and without. Likewise, further subdivision of the PBB group in euploid and aneuploid embryos revealed no differences in the early embryo morphokinetic development compared to the control group. Aneuploidy testing revealed a high prevalence of chromosomal aberrations for chromosomes 21, 4, 16, and 19. CONCLUSIONS: In conclusion, PBB does not impact the morphokinetic parameters of the embryo development. PBB can be safely applied without the risk of impairing the reproductive potential of the embryo and can be highly recommended as safe and practicable PGT approach, especially in countries with prevailing restrictions regarding PGT analysis. PMID- 29790074 TI - Attentional modulation of desensitization to odor. AB - Subjective and behavioral responsiveness to odor diminishes during prolonged exposure. The precise mechanisms underlying olfactory desensitization are not fully understood, but previous studies indicate that the phenomenon may be modulated by central-cognitive processes. The present study investigated the effect of attention on perceived intensity during exposure to a pleasant odor. A within-subjects design was utilized with 19 participants attending 2 sessions. During each session, participants continuously rated their perceived intensity of a 10-minute exposure to a pleasant fragrance administered using an olfactometer. An auditory oddball task was implemented to manipulate the focus of attention in each session. Participants were instructed to either direct their attention toward the sounds, but still to rate odor, or to focus entirely on rating the odor. Analysis revealed three 50-second time windows with significantly lower mean intensity ratings during the distraction condition. Curve fitting of the data disclosed a linear function of desensitization in the focused attention condition compared with an exponential decay function during distraction condition, indicating an increased rate of initial desensitization when attention is distracted away from the odor. In the focused-attention condition, perceived intensity demonstrated a regular pattern of odor sensitivity occurring at approximately 1-2 minutes intervals following initial desensitization. Spectral analysis of low-frequency oscillations confirmed the presence of augmented spectral power in this frequency range during focused relative to distracted conditions. The findings demonstrate for the first time modulation of odor desensitization specifically by attentional factors, exemplifying the relevance of top-down control for ongoing perception of odor. PMID- 29790073 TI - Effect of Low Back Pain Risk-Stratification Strategy on Patient Outcomes and Care Processes: the MATCH Randomized Trial in Primary Care. AB - BACKGROUND: The STarT Back strategy for categorizing and treating patients with low back pain (LBP) improved patients' function while reducing costs in England. OBJECTIVE: This trial evaluated the effect of implementing an adaptation of this approach in a US setting. DESIGN: The Matching Appropriate Treatments to Consumer Healthcare needs (MATCH) trial was a pragmatic cluster randomized trial with a pre-intervention baseline period. Six primary care clinics were pair randomized, three to training in the STarT Back strategy and three to serve as controls. PARTICIPANTS: Adults receiving primary care for non-specific LBP were invited to provide data 2 weeks after their primary care visit and follow-up data 2 and 6 months (primary endpoint) later. INTERVENTIONS: The STarT Back risk stratification strategy matches treatments for LBP to physical and psychosocial obstacles to recovery using patient-reported data (the STarT Back Tool) to categorize patients' risk of persistent disabling pain. Primary care clinicians in the intervention clinics attended six didactic sessions to improve their understanding LBP management and received in-person training in the use of the tool that had been incorporated into the electronic health record (EHR). Physical therapists received 5 days of intensive training. Control clinics received no training. MAIN MEASURES: Primary outcomes were back-related physical function and pain severity. Intervention effects were estimated by comparing mean changes in patient outcomes after 2 and 6 months between intervention and control clinics. Differences in change scores by trial arm and time period were estimated using linear mixed effect models. Secondary outcomes included healthcare utilization. KEY RESULTS: Although clinicians used the tool for about half of their patients, they did not change the treatments they recommended. The intervention had no significant effect on patient outcomes or healthcare use. CONCLUSIONS: A resource intensive intervention to support stratified care for LBP in a US healthcare setting had no effect on patient outcomes or healthcare use. TRIAL REGISTRATION: National Clinical Trial Number NCT02286141. PMID- 29790072 TI - Effect of Social Comparison Feedback on Laboratory Test Ordering for Hospitalized Patients: A Randomized Controlled Trial. AB - BACKGROUND: Social comparison feedback is an increasingly popular strategy that uses performance report cards to modify physician behavior. Our objective was to test the effect of such feedback on the ordering of routine laboratory tests for hospitalized patients, a practice considered overused. METHODS: This was a single blinded randomized controlled trial. Between January and June 2016, physicians on six general medicine teams at the Hospital of the University of Pennsylvania were cluster randomized with equal allocation to two arms: (1) those e-mailed a summary of their routine laboratory test ordering vs. the service average for the prior week, linked to a continuously updated personalized dashboard containing patient-level details, and snapshot of the dashboard and (2) those who did not receive the intervention. The primary outcome was the count of routine laboratory test orders placed by a physician per patient-day. We modeled the count of orders by each physician per patient-day after the intervention as a function of trial arm and the physician's order count before the intervention. The count outcome was modeled using negative binomial models with adjustment for clustering within teams. RESULTS: One hundred and fourteen interns and residents participated. We did not observe a statistically significant difference in adjusted reduction in routine laboratory ordering between the intervention and control physicians (physicians in the intervention group ordered 0.14 fewer tests per patient-day than physicians in the control group, 95% CI - 0.56 to 0.27, p = 0.50). Physicians whose absolute ordering rate deviated from the peer rate by more than 1.0 laboratory test per patient-day reduced their laboratory ordering by 0.80 orders per patient-day (95% CI - 1.58 to - 0.02, p = 0.04). CONCLUSIONS: Personalized social comparison feedback on routine laboratory ordering did not change targeted behavior among physicians, although there was a significant decrease in orders among participants who deviated more from the peer rate. TRIAL REGISTRATION: Clinicaltrials.gov registration: #NCT02330289. PMID- 29790075 TI - Pathways from Resilient Coping to Safer Sex Communication Among African, Caribbean, and Black Women in Toronto, Canada: Results from a Cross-sectional Survey. AB - PURPOSE: African, Caribbean, and Black (ACB) women in Canada are disproportionately impacted by HIV and other sexually transmitted infections. Although there is reported suboptimal consistent condom use with ACB women, limited research has explored safer sex communication among this population. Coping frameworks highlight the role that resilient coping and condom use self efficacy may play in facilitating safer sex communication. Structural perspectives stress the need to explore associations between HIV vulnerabilities and food insecurity. We examined pathways from resilient coping to safer sex communication through the mediator of condom use self-efficacy among ACB women in Toronto. METHOD: We conducted a cross-sectional survey with a purposive sample of ACB women aged 16 and older across Toronto, Canada. We conducted path analysis to test the direct effects of resilient coping on safer sex communication, and indirect pathways through the mediator (condom use self-efficacy) while controlling for food insecurity. RESULTS: Participant (n = 80; mean age 27, SD 7.93) ethnicities included African (58.8%, n = 47), Caribbean (30%, n = 24), and others (11.3%, n = 9). Participants with food security reported significantly higher safer sex communication. We found no direct effect of resilient coping on safer sex communication. Findings support the hypothesized mediation process; resilient coping was associated with condom use self-efficacy, which in turn was associated with safer sex communication. CONCLUSION: Findings that condom use self-efficacy mediated the association between resilient coping and safer sex communication align with theoretical assertions of the protective role of adaptive coping strategies. Findings can inform tailored HIV and STI preventive interventions with ACB women. PMID- 29790076 TI - A case of Jackhammer esophagus caused by eosinophilic esophagitis in which per oral endoscopic myotomy resulted in symptom improvement. AB - A 73-year-old female with a 6-month history of progressive dysphagia and chest pain was referred to our hospital. She underwent esophagogastroduodenoscopy, which revealed abnormally strong contractions in the distal esophagus. Esophageal biopsy specimens showed massive eosinophil infiltration into the epithelium, and high-resolution manometry (HRM) also demonstrated abnormally strong contractions in the distal esophagus. Based on these results, she was diagnosed with Jackhammer esophagus (JHE) due to eosinophilic esophagitis (EoE). Treatment was started with 5 mg/day of prednisolone (PSL), and the number of peripheral blood eosinophils quickly decreased without any improvement in the patient's dysphagia. Esophageal biopsy specimens obtained after the PSL treatment showed the disappearance of eosinophils from the epithelium. However, abnormally strong contractions were still detected on HRM. Per-oral endoscopic myotomy (POEM) was performed to treat the JHE. Interestingly, the intraoperative esophageal muscle biopsy sample demonstrated massive eosinophil infiltration into the muscle layer. After the POEM, the patient's symptoms improved, and abnormal contractions were no longer detected on HRM. The current case suggests that when EoE combined with an esophageal motility disorder are refractory to steroid therapy, clinicians should be aware that motility disorders can develop due to eosinophil infiltration deep into the esophageal muscularis propria. PMID- 29790077 TI - From ideas to long-term studies: 3D printing clinical trials review. AB - PURPOSE: Although high costs are often cited as the main limitation of 3D printing (3DP) in the medical field, current lack of clinical evidence is asserting itself as an impost as the field begins to mature. The aim is to review clinical trials in the field of 3DP, an area of research which has grown dramatically in recent years. METHODS: We surveyed clinical trials registered in 15 primary registries worldwide, including ClinicalTrials.gov. All trials which utilized 3DP in a clinical setting were included in this review. Our search was performed on December 15, 2017. Data regarding the purpose of the study, inclusion criteria, number of patients enrolled, primary outcomes, centers, start and estimated completion dates were extracted. RESULTS: A total of 92 clinical trials with [Formula: see text]252 patients matched the criteria and were included in the study. A total of 42 (45.65%) studies cited China as their location. Only 10 trials were multicenter and 2 were registered as international. The discipline that most commonly utilized 3DP was Orthopedic Surgery, with 25 (27.17%) registered trials. At the time of data extraction, 17 (18.48%) clinical trials were complete. CONCLUSIONS: After several years of case reports, feasibility studies and technical reports in the field, larger-scale studies are beginning to emerge. There are almost no international register entries. Although there are new emerging areas of study in disciplines that may benefit from 3DP, it is likely to remain limited to very specific applications. PMID- 29790078 TI - A PRM approach for early prediction of breast cancer response to chemotherapy based on registered MR images. AB - PURPOSE: This study aims to provide and optimize a performing algorithm for predicting the breast cancer response rate to the first round of chemotherapy using Magnetic Resonance Imaging (MRI). This provides an early recognition of breast tumor reaction to chemotherapy by using the Parametric Response Map (PRM) method. METHODS: PRM may predict the breast cancer response to chemotherapy by analyzing voxel-by-voxel temporal intra-tumor changes during one round of chemotherapy. Indeed, the tumor recognizes intra-tumor changes concerning its vascularity, which is an important criterion in the present study. This method is mainly based on spatial image affine registration between the breast tumor MRI volumes, acquired before and after the first cycle of chemotherapy, and region growing segmentation of the tumor volume. To evaluate our method, we used a retrospective study of 40 patients provided by a collaborating institute. RESULTS: PRM allows a color map to be created with the percentages of positive, negative and stable breast tumor response during the first round of chemotherapy, identifying each region with its response rate. We assessed the accuracy of the proposed method using technical and medical validation methods. The technical validation was based on landmarks-based registration and fully manual segmentation. The medical evaluation was based on the accuracy calculation of the standard reference of anatomic pathology. The p-values and the Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated to evaluate the proposed PRM method. CONCLUSION: We performed and evaluated the proposed PRM method to study and analyze the behavior of a tumor during the first round of chemotherapy, based on the intra-tumor changes of MR breast tumor images. The AUC obtained for the PRM method is considered as relevant in the early prediction of breast tumor response. PMID- 29790079 TI - Impact of Spirituality/Religiousness on Cyber Bullying and Victimization in University Students: Mediating Effect of Emotional Intelligence. AB - The aim of the study was to explore the relationship between spirituality/religiousness with cyber bullying and victimization amongst Indian University students and whether emotional intelligence mediates the relationship. Data were collected from 490 University students studying in undergraduate and postgraduate courses across India. IBM AMOS was used to find reliability and validity of instruments and PROCESS macro for IBM SPSS by Preacher and Hayes (Behav Res Methods 36(4): 717-731, 2004) was used for conducting mediation analyses. Both spiritual and existential well-being were found negatively related with cyber bullying and victimization. As far as mediation goes, the negative relationships between spiritual and existential well-being with that of cyber bullying and victimization were significantly mediated by Appraisal of Self Emotions, Appraisal of Other's Emotions and Regulation and control of Emotions dimensions of emotional intelligence. Implication and future directions are also discussed. PMID- 29790080 TI - Religion and Body Weight Among African-American Adults Attempting to Lose Weight: An Exploratory Study. AB - Religion and body weight was explored at two time points among overweight and obese African-American adults. Baseline and follow-up data were collected from 26 adults participating in a weight loss intervention and analyzed using multiple regression analyses of religious measures, body weight, and other variables. Frequent church attendance was significantly associated with greater weight lost from baseline to 16-week follow-up. In this exploratory study, religious interactions and experiences may be involved in shaping body weight among African Americans attempting to lose weight. PMID- 29790081 TI - Transplant renal vein thrombosis in a recipient with aberrant venous anatomy. AB - Renal vein thrombosis in a transplanted kidney is an uncommon but critical complication that can result in graft loss if management is delayed. A 31-year old male with known atresia of the inferior vena cava who received a deceased donor renal transplant 7 years previously presented to hospital with severe graft site pain and a week of nausea, vomiting, and chills. Serum creatinine was markedly elevated from baseline. Sonographic examination revealed external iliac vein thrombosis with extension of the thrombus into the transplant renal vein. Urgent angiographic administration of tissue plasminogen activator and suction thrombectomy was performed, then followed by heparin and clopidogrel post procedure. Within 24 h, his serum creatinine improved, and within 2 weeks returned to his baseline. He was started on lifelong warfarin anti-coagulation to reduce the risk of rethrombosis secondary to his uncorrectable aberrant venous anatomy. Due to the turbulent and sometimes reversed flow in the major veins, lifelong anticoagulation should be strongly considered for such transplant patients with recipient aberrancy of the large veins. PMID- 29790082 TI - Chronic Administration of Pimozide Fails to Attenuate Motor and Pathological Deficits in Two Mouse Models of Amyotrophic Lateral Sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which presently does not have any efficient therapeutic approach. Pimozide, a Food and Drug Administration (FDA)-approved neuroepileptic drug, has been recently proposed as a promising treatment for ALS patients based on apparent stabilization of right hand muscles after a short-time administration. A new clinical trial started at the end of 2017 to recruit patients with a prolonged drug delivery schedule. Here, our aim was to investigate the effects of chronic administration of pimozide on disease progression and pathological events in two mouse models of ALS. Pimozide was administered every 2 days to transgenic mice bearing the ALS-linked A315T mutation on the human TAR DNA-binding protein 43 (TDP-43) gene and to mice carrying the human superoxide dismutase 1 (SOD1) gene with the ALS-linked G93A mutation. Chronic administration of pimozide exacerbated motor performances in both animal models and reduced survival in SOD1G93A mice. In TDP-43A315T, it decreased the percentage of innervated neuromuscular junctions (NMJs) and increased the accumulation of insoluble TDP-43. In SOD1G93A mice, pimozide had no effects on NMJ innervation or motoneuron loss, but it increased the levels of misfolded SOD1. We conclude that a chronic administration of pimozide did not confer beneficial effects on disease progression in two mouse models of ALS. In light of a new clinical trial on ALS patients with a chronic regime of pimozide, these results with mouse models suggest prudence and careful monitoring of ALS patients subjected to pimozide treatment. PMID- 29790083 TI - Point quantification elastography in the evaluation of liver elasticity in healthy volunteers: a reliability study based on operator expertise. AB - PURPOSE: The assessment of liver fibrosis is essential in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard procedure for this purpose, though the recent development of new elastosonographic techniques to measure liver stiffness (LS) noninvasively is promising. Point quantification elastography (PQE) showed good results but less is known about the level of skill needed to obtain reliable results. The aim of the study was to evaluate the reproducibility of PQE in assessing LS in healthy subjects comparing three operators with different expertise. METHODS: Between December 2012 and April 2013, 50 consecutive healthy volunteers (18 males, 32 females), median age 30 years (range 25-66) and BMI 22.4 (range 16.7-33.6) were submitted to PQE (iU22 Philips, Bothell, WA, USA) by three operators: two US and elastography providers (one expert and one with intermediate skill) and a skilled transient elastography (Fibroscan) operator with no expertise in US. Intra- and inter-observer agreements were assessed by intraclass correlation coefficient (ICC). RESULTS: PQE measurement was obtained in all subjects by all evaluators. No significant differences of mean liver stiffness were found among operators (P = 0.980). Intra-observer agreement was excellent 0.918 (0.941 for expert, 0.917 for intermediate and 0.888 for novice). The ICC of the inter-observer agreement among the three ratters was excellent (0.882) and was higher in normal than overweight patients (0.923 vs. 0.603; P = 0.011). CONCLUSION: PQE is a reliable and reproducible non-invasive method for the assessment of LE, and can be performed also by a non-experienced operator. PMID- 29790084 TI - Cloning and expression of nlpA gene as DNA vaccine candidate against Acinetobacter baumannii. AB - Acinetobacter baumannii is one of the highly antibiotic-resistant bacteria that cause infections with high rate of death. This bacterium is one the common causes of infection worldwide leading to endemic and epidemic nosocomial infections. Despite many efforts, there is no effective vaccine against A. baumannii. As NlpA is one of the important antigenic factors in biogenesis of outer membrane vesicles, and OMV-based reported vaccines in A. baumannii stimulated the immune responses, this study was aimed to clone and express nlpA gene in eukaryotic HDF cells and evaluate the induced immunization following the administration of resulting construct as DNA vaccine in BALB/c mice. The nlpA gene of A. baumannii was amplified using PCR. The PCR product was then cloned and subcloned into the pTZ57R/T and pEGFP-C2 vectors respectively. The cloning was confirmed by PCR, restriction enzyme digestion and DNA sequencing. The pEGFP-C2-nlpA recombinant plasmid was transferred into the HDF cells using electroporation and the expression of target gene was validated by RT-PCR. The recombinant construct was injected to BALB/c mice through three IM injections and the levels of IgG, IgM, INF-gamma, IL-2, IL-4, and IL-12 were determined using ELISA assay. The A. baumannii nlpA gene was amplified during PCR as 867 bp band which was successfully cloned in pEGFP-C2-nlpA vector. Obtained data from RT-PCR and presence of the 867 bp fragment in transformed HDF cells confirmed the nlpA gene expression. Following the injection of pEGFP-C2-nlpA showed the increased level of IgG, IgM, INF-gamma, IL-2, IL-4, and IL-12 in serum of immunized mice. Overall, through this study recombinant pEGFP-C2-nlpA was generated and successfully expressed the A. baumannii nlpA gene in eukaryotic cells. Additionally, our in vivo study confirmed that the recombinant construct capable to induce the immune response in immunized mice. These findings suggest the pEGFP C2-nlpA may be considered as DNA vaccine candidate against A. baumannii. PMID- 29790085 TI - White Matter Microstructure in Bipolar Disorder Is Influenced by the Interaction between a Glutamate Transporter EAAT1 Gene Variant and Early Stress. AB - Glutamate is the principal excitatory neurotransmitter in the central nervous system. In mature brains, it is critically involved in neuroplasticity and, at high levels, neurotoxicity. The concentrations of glutamate in the extracellular space are maintained at low physiological levels by molecular glutamate transporters (excitatory amino acid transporters-EAATs). Adverse childhood experiences (ACEs) are highly reported in bipolar disorder (BD) and interact with the glutamatergic system in the brain. The aim of the study is to investigate the effect of a glutamate transporter polymorphism EAAT2-181A > C (rs4354668) and exposure to ACE on white matter microstructure in patients with BD. We assessed 175 bipolar subjects using diffusion tensor imaging, Risky Families Questionnaire, and EEAT2 rs4354668 variants. We observed an interaction between ACE and rs4354668: carriers of the G allele showed lower axial diffusivity compared to T/T homozygotes when exposed to high stress and higher axial diffusivity than T/T when exposed to low stress. Since the mutant G allele has been associated with a reduced transcriptional activity and expression of the transporter protein, and early stress is associated with a reduced expression of the EAAT2, we could hypothesize that after exposure to high levels of ACE G/G homozygotes are more vulnerable to stress reporting the highest damage as a consequence of an excess of free glutamate. PMID- 29790086 TI - Testosterone-mediated activation of androgenic signalling sustains in vitro the transformed and radioresistant phenotype of rhabdomyosarcoma cell lines. AB - PURPOSE: Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. METHODS: Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR. Radiation treatment was delivered to characterise the effects of T treatment on RMS intrinsic radioresistance. RESULTS: Our study showed that RMS cells respond to sub-physiological levels of T stimulation, finally promoting AR-dependent genomic and non-genomic effects, such as the transcriptional regulation of several oncogenes, the phosphorylation-mediated post-transductional modifications of AR and the activation of ERK, p38 and AKT signal transduction pathway mediators that, by physically complexing or not with AR, participate in regulating its transcriptional activity and the expression of T-targeted genes. T chronic daily treatment, performed as for the hormone circadian rhythm, did not significantly affect RMS cell growth, but improved RMS clonogenic and radioresistant potential and increased AR mRNA both in ERMS and ARMS. AR protein accumulation was evident in ERMS, this further developing an intrinsic T-independent AR activity. CONCLUSIONS: Our results suggest that androgens sustain and improve RMS transformed and radioresistant phenotype, and therefore, their therapeutic application should be avoided in RMS post puberal patients. PMID- 29790087 TI - Correlation Between Clinical and Pathologic Staging in Colon Cancer: Implications for Neoadjuvant Treatment. AB - BACKGROUND: Recent randomized trials suggest improved outcomes in patients with locally advanced colon cancer (LACC) treated with neoadjuvant chemotherapy (NAC). Optimal selection of patients for NAC depends on accurate clinical staging. The purpose of this study was to examine the degree of correlation between clinical and pathologic staging in patients with colon cancer (CC). METHODS: Adult patients with non-metastatic CC who underwent surgery were identified from the National Cancer Data Base between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. RESULTS: One hundred five thousand five hundred sixty-nine patients were identified. The overall correlation rate between clinical and pathologic staging for T stage was 80% (kappa 0.7) and 83% for N stage (kappa 0.6). The correlation rate was 54% for T1, 76% for T2, 95% for T3, and 94% for T4 (P < 0.001). This compared with 81% for N0, 82% for N1, and 97% for N2 (P < 0.001). The sensitivity and specificity of clinical staging for identifying T3/T4 vs T1/T2 were 80 and 98%, respectively, compared to 60 and 98% for N1/N2 vs N0 (P < 0.001). CONCLUSIONS: Our findings suggest that current modalities used for clinical staging are accurate in predicting pathologic stage for advanced but not early T and N disease. Further optimization of clinical staging is essential for the accurate selection of patients who may benefit from neoadjuvant therapy and to avoid overtreatment of low-risk patients. PMID- 29790088 TI - Three New Heptelidic Acid Derivatives from the Culture of Mushroom Lentinellus ursinus. AB - Three new heptelidic acid derivatives (1-3) including two new dimeric esters and two known heptelidic acid analogues (4 and 5) were isolated from the solid culture of mushroom Lentinellus ursinus. The structures of new compounds were confirmed by the analysis of NMR and HRESIMS spectroscopic data. The biosynthetic origin of compounds 1-5 was postulated. Compounds 1-5 exhibited no antibacterial activity against Staphylococcus aureus and Escherichia coli at the dose of 100 MUM. PMID- 29790089 TI - Red drum Sciaenops ocellatus growth and expression of bile salt-dependent lipase in response to increasing dietary lipid supplementation. AB - Sciaenops ocellatus has a long history in aquaculture and many difficulties associated with its commercial culture have been addressed and successfully resolved; nevertheless, further research in lipid nutrition could address more comprehensive questions on the way these nutrients are utilized. The purpose of this study was to evaluate S. ocellatus growth and lipase gene expression in response to increasing dietary lipid supplementation. Four experimental diets were formulated to provide 3, 10, 16, or 23% lipid using menhaden fish oil. Twenty juveniles (mean initial weight 2.3 +/- 0.1 g) were stocked per aquaria in a recirculating system; each diet was assigned to three aquaria and fed to fish for 6 weeks. At the end of the study, fish fed 3% of dietary lipid were significantly (P < 0.0001) smaller and showed significantly lower feed efficiency, condition factor, hepatosomatic index, and intraperitoneal fat than fish fed the other diets, but no differences were observed among fish fed 10, 16, or 23% lipid. A straight broken-line regression model for thermal growth coefficient provided an estimated value of 9.4% of dietary lipid as the optimal inclusion level. The bile salt-dependent lipase (BSDL) of red drum was 80.3 kDa. Relative gene expression of BSDL was significantly higher (P = 0.0007) in fish fed 10% lipid, with no differences among the other dietary treatments. Results provided could help monitor the metabolic status of farmed fish and contribute to optimize diet formulations based on maximum gene expression of BSDL for supplementation of dietary lipid. PMID- 29790090 TI - Enhancement of broodstock health and maternal immunity in gilthead seabream (Sparus aurata L.) using ExcelMOS(r). AB - The current study was conducted to investigate the effect of ExcelMOS(r) in enhancing the immune system of Sparus aurata broodstock and their impact on offspring health through displaying the maternal transfer of immunity. Broodstock were divided into two groups: one was injected intraperitoneally with ExcelMOS(r) 1 month before spawning, while the other group was used as a control (without injection). Comprehensive increase in survival rate was observed for larvae hatched from ExcelMOS(r)-injected broodstock than those of the control (P <= 0.05). Hematological analysis showed increases in leukocyte count and hematocrit percentage (P <= 0.05) and significant enhancement in immune assays as phagocytic, respiratory burst, lysozyme activities in ExcelMOS(r)-injected broodstock (P <= 0.05). Additionally, total immunoglobulin levels in the serum, eggs, and larvae resulted from ExcelMOS(r)-injected broodstock were highly significant (P <= 0.05) than those in the control ones. Transmission electron microscopy and semi-thin sections in posterior intestine of ExcelMOS(r)-injected broodstock revealed reinforcement of the epithelial barrier structure, intestinal integrity, and functionality in combination with the stimulation of innate immune system. In conclusion, immunostimulation of Sparus aurata broodstock using ExcelMOS(r) has improved survival of larvae and enhanced both innate and adaptive immune defense mechanisms. Further investigations are required to show the effect of ExcelMOS(r) on fish cultured in intensive culture systems. PMID- 29790091 TI - Effects of acute hyperglycemia stress on plasma glucose, glycogen content, and expressions of glycogen synthase and phosphorylase in hybrid grouper (Epinephelus fuscoguttatus ? * E. lanceolatus ?). AB - In the present study, the hybrid grouper (Epinephelus fuscoguttatus ? * E. lanceolatus ?), a typical carnivorous fish, was chosen as a model to investigate the regulation of glycogen metabolism owning to its characteristic of glucose intolerance. The variation of plasma glucose concentration, glycogen content, and expressions of glycogen metabolism-related genes under acute hyperglycemia stress were measured. Following glucose administration, plasma glucose concentration increased immediately, and the glucose level remained elevated for at least 12 h. The prolonged glucose clearance and hyperglycemia revealed glucose intolerance of this fish species. Meanwhile, the glycogen content in both liver and muscle changed significantly during the clearance of plasma glucose. However, the peak value of hepatic glycogen (1 and 12 h post injection) appeared much earlier than muscle (3 and 24 h post injection). To investigate the regulation of glycogen metabolism from molecular aspect, the complete coding sequence (CDS) of glycogen synthase (GS) and glycogen phosphorylase (GP) in both liver and muscle types were obtained, encoding a polypeptide of 704, 711, 853, and 842 amino acid residues, respectively. The results of gene expression analysis revealed that the expression of liver type and muscle type GS was significantly higher than other time points at 12 and 24 h post glucose injection, respectively. Meanwhile, the highest expressions of GP in both liver and muscle types occurred at 24 h post glucose injection. The response of GS and GP to glucose load may account for the variation of glycogen content at the transcriptional level to some extent. PMID- 29790093 TI - Erratum to: Decellularization Methods for Scaffold Fabrication. AB - The publisher regrets that an author was not mentioned in the chapter by mistake. The details of the author are provided below:Archna Dhasmana - Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee, India. PMID- 29790092 TI - Effects of olive leaf powder supplemented to fish feed on muscle protein of red sea bream. AB - Olive leaf is known to have the high polyphenol content of 6-9% in dry weight. We investigated the effects of olive leaf powder (OLP) supplemented to fish feed on muscle protein of red sea bream (Pagrus major). Fish reared with feed containing 8% OLP for 40 days had 1.4 times higher myofibril content and 2.2 times higher acid-soluble collagen content than fish reared with control feed for the same period. On the other hand, sarcoplasmic protein content and collagenase activity of the muscle were almost the same between the control fish and OLP-diet fish. Microstructure observation of fish muscle showed that OLP-diet fish has more rigid endomysium structure than that of the control-diet fish. Since collagen fiber in endomysium is responsible for the texture of the muscle, feeding OLP to aquaculture fish will lead to a harder muscle texture. The present study suggests that OLP is a useful feed additive to enhance the texture of aquaculture red sea bream muscle through strengthening of the collagen structure in the muscle. PMID- 29790094 TI - Isolation of Cancer Stem Cells from Squamous Cell Carcinoma. AB - Different cancer stem cell (CSC) populations can be found in many types of cancer, including squamous cell carcinoma (SSC). Diverse reports showed that CSC play a crucial role in the relapse of different types of cancer. CSC sustains tumor growth due to their capacity to self-renew and their potential to initiate secondary tumors with metastatic cancer features. Therefore, the development of methods for the isolation of CSC is a key step to explore the mechanisms underlying CSC maintenance. In this chapter, we provide a method for isolating CSC from cutaneous SSC using immunofluorescence labeling to allow the specific purification of CSC by fluorescence-activated cell sorting (FACS). This method is based on the use of CSC membrane markers, allowing as well the isolation CSC from different mouse strains. PMID- 29790095 TI - Full-Thickness Human Skin Equivalent Models of Atopic Dermatitis. AB - Atopic dermatitis is a chronic inflammatory skin disease caused by complex multifactorial etiology. In the recent years, there have been significant advances in tissue engineering and the generation of in vitro skin models representative of healthy and diseased states. This chapter describes the methodology for the fabrication of in vitro human skin equivalent (HSE) from human keratinocytes and fibroblasts using a fibrin-based dermal matrix and serum free culture conditions. Modification of the culture conditions with the supplementation of Th2 cytokines such as interleukin-4 induces the development of atopic dermatitis-like skin model. The chapter also describes the histological and immunohistochemical tools for characterization of the HSE model. The reconstruction of tissue-engineered HSE models that recapitulate the essential features of atopic dermatitis provides powerful tools for deeper understanding of the underlying pathological mechanisms on epidermal level, identification and testing of novel treatment options, and safety and toxicological evaluation in a pathophysiologically relevant system. PMID- 29790096 TI - Metabolomic and Proteomic Analyses of Mouse Primordial Germ Cells. AB - Primordial germ cells (PGCs), the precursors of gametes, are the only cells capable of acquiring totipotency upon fertilization, but the molecular mechanisms regulating germ cell characteristics have not been fully elucidated. Although intracellular metabolic status and regulation are responsible for the control of cell function and differentiation, little is known about the metabolic features of PGCs. Here, we describe use of an integrated metabolomic, proteomic, and energy metabolic analysis method to comprehensively elucidate the metabolic characteristics of PGCs using mass spectrometry. PMID- 29790097 TI - Sex differences in navigation strategy and efficiency. AB - Research on human navigation has indicated that males and females differ in self reported navigation strategy as well as objective measures of navigation efficiency. In two experiments, we investigated sex differences in navigation strategy and efficiency using an objective measure of strategy, the dual-solution paradigm (DSP; Marchette, Bakker, & Shelton, 2011). Although navigation by shortcuts and learned routes were the primary strategies used in both experiments, as in previous research on the DSP, individuals also utilized route reversals and sometimes found the goal location as a result of wandering. Importantly, sex differences were found in measures of both route selection and navigation efficiency. In particular, males were more likely to take shortcuts and reached their goal location faster than females, while females were more likely to follow learned routes and wander. Self-report measures of strategy were only weakly correlated with objective measures of strategy, casting doubt on their usefulness. This research indicates that the sex difference in navigation efficiency is large, and only partially related to an individual's navigation strategy as measured by the dual-solution paradigm. PMID- 29790098 TI - Three-step method for transesophageal echocardiography-guided implantation of the frozen elephant trunk: how to prevent spinal cord injury. AB - Total aortic arch replacement using the frozen elephant trunk (FET) procedure has widely spread all over the world with more sophisticated devices. However, spinal cord injury is one of the most important complications, which limits the use of FET. In our hospital, 80 patients treated with FET had no spinal cord injury. There are three key points to avoid spinal cord injury, (1) The distal end of stent graft should be positioned up to the eighth thoracic vertebrae level; (2) the time for selective left subclavian artery perfusion and distal body circulatory arrest should be shortened within 60 min; and (3) mean blood pressure should be maintained above 70 mmHg. Especially, Key point (1) is the most important. The level of aortic valve, which locates around the seventh thoracic vertebrae level, is an appropriate benchmark. We implanted the stent graft with the use of transesophageal echocardiography guided three-step method. PMID- 29790099 TI - The changes underwent by free fat pads used for pulmonary air leakage repair. AB - The use of free fat pads is effective for repairing pulmonary air leakage clinically. It has been reported that the free pericardial fat pad (FPFP) used to repair the lung remained at the transplanted site in many cases according to images. However, no information is available regarding what type of actual changes these free fat pads with no blood supply undergo. We examined changes in an FPFP that was used to repair pulmonary air leakage in a patient who underwent a surgery for lung cancer 1 year ago. Although the FPFP transplanted to the pleural defect remained without deforming morphologically in this patient 1 year after the first surgery, pathological findings suggested fat necrosis surrounded by fibrous tissue. Our findings suggest that while free fat pads used for pulmonary air leakage repair presumably are not engrafted, they should remain on the lung surface in a thoracolithiasis-like condition. PMID- 29790101 TI - Medical Student Exposure to Integrated Behavioral Health. AB - OBJECTIVE: Integrated behavioral health (IBH) allows for effective care delivery for patients with mental health and behavioral health disorders in primary care settings. This study assesses the state of exposure current medical students have to the IBH model in family medicine clerkships, in order to augment the readiness of students to participate in IBH as developing professionals. METHODS: Clerkship directors at US and Canadian medical schools with a required family medicine run course (n = 141) were asked to estimate the percentage of students exposed to IBH in their clerkships, as part of the Council of Academic Family Medicine Educational Research Alliance (CERA) 2016 survey. RESULTS: The response rate was 86% (n = 118). Forty-four percent of clerkship directors reported that 0-20% of students are exposed to the IBH model in their clerkships. A comparison of schools with low and high exposure showed no significant differences among clerkship characteristics. CONCLUSIONS: A majority of medical students in the USA and Canada are not exposed to IBH models during their primary care clerkship. Larger systematic studies are needed to elucidate the steps necessary to prepare graduating medical students to collaborate in IBH models. PMID- 29790102 TI - Classification of malignant and benign lung nodules using taxonomic diversity index and phylogenetic distance. AB - Lung cancer presents the highest cause of death among patients around the world, in addition of being one of the smallest survival rates after diagnosis. Therefore, this study proposes a methodology for diagnosis of lung nodules in benign and malignant tumors based on image processing and pattern recognition techniques. Mean phylogenetic distance (MPD) and taxonomic diversity index (Delta) were used as texture descriptors. Finally, the genetic algorithm in conjunction with the support vector machine were applied to select the best training model. The proposed methodology was tested on computed tomography (CT) images from the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI), with the best sensitivity of 93.42%, specificity of 91.21%, accuracy of 91.81%, and area under the ROC curve of 0.94. The results demonstrate the promising performance of texture extraction techniques using mean phylogenetic distance and taxonomic diversity index combined with phylogenetic trees. Graphical Abstract Stages of the proposed methodology. PMID- 29790100 TI - The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression. AB - NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981. Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25 6981 was administered (protocol days 6-7) followed by retraining (days 15-18 or 29-32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol. Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29-32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment. Chronological analysis indicated a possible involvement of new mature neurons in the reconfiguration of memory processes. This was attended by behavioral/gene correlations which revealed direct links between spatial memory retrieval enhancement and modified gene activity induced by NR2B/NMDA receptor blockade and upregulation. PMID- 29790103 TI - Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. AB - BACKGROUND: Stimulant medications for the treatment of attention deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on treatment assessment from a higher weight category at baseline. At the last on treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756. PMID- 29790104 TI - Beneficial Effects of Antioxidant Furfuryl Palmitate in Non-pharmacologic Treatments (Prescription Emollient Devices, PEDs) for Atopic Dermatitis and Related Skin Disorders. AB - INTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory skin disease; it requires long-term treatments focused on symptomatic relief. Current first-line treatments include moisturizers and topical corticosteroids. Recently, topical antioxidants have been added to moisturizer formulations to alleviate mild-to-moderate AD. The aim of this review was to evaluate the efficacy and tolerability of furfuryl palmitate, a new antioxidant molecule, and furfuryl derivatives. METHODS: A PubMed/Google Scholar search was conducted using the term "furfuryl palmitate" (and its derivatives, including AR-GG27(r)) combined with "skin," "atopic dermatitis," and "atopic eczema." Existing trials including adult and pediatric patients with AD and related skin disorders were evaluated. The treatment indication(s), number of subjects, treatment protocols, results, and side effects were recorded. RESULTS: Effective treatments with furfuryl palmitate and furfuryl derivatives have been reported for the following conditions: atopic, seborrheic, irritative, and allergic contact dermatitis, eczema, xerosis, and cutaneous inflammatory pathologies. All the products tested showed a good tolerability profile. CONCLUSION: Studies performed up to now showed that furfuryl derivatives can efficaciously contrast signs and symptoms of mild-to moderate AD, erythema, and widespread diffuse cutaneous pathologies in both adult and pediatric patients, representing a real alternative to steroids and a valid aid in the treatment of skin disorders, with no side effects and without requiring precautions in use. FUNDING: Relife S.r.l. - Menarini Group. Plain language summary available for this article. PMID- 29790105 TI - Physostigmine Restores Impaired Autophagy in the Rat Hippocampus after Surgery Stress and LPS Treatment. AB - Tissue damage and pathogen invasion during surgical trauma have been identified as contributing factors leading to neuroinflammation in the hippocampus, which can be protected by stimulation of the cholinergic anti-inflammatory pathway using the acetylcholinesterase inhibitor physostigmine. Macroautophagy, an intracellular degradation pathway used to recycle and eliminate damaged proteins and organelles by lysosomal digestion, seems to be important for cell survival under stress conditions. This study aimed to examine the role of autophagy in physostigmine-mediated hippocampal cell protection in a rat model of surgery stress. In the presence or absence of physostigmine, adult Wistar rats underwent surgery in combination with lipopolysaccharide (LPS). Activated microglia, apoptosis-, autophagy-, and anti-inflammatory-related genes and -proteins in the hippocampus were determined by Real-Time PCR, Western blot and fluorescence microscopy after 1 h, 24 h and 3 d. Surgery combined with LPS-treatment led to microglia activation after 1 h and 24 h which was accompanied by apoptotic cell death after 24 h in the hippocampus. Furthermore, it led to a decreased expression of ATG-3 after 24 h and an increased expression of p62/ SQSTM1 after 1 h and 24 h. Administration of physostigmine significantly increased autophagy related markers and restored the autophagic flux after surgery stress, detected by increased degradation of p62/ SQSTM1 in the hippocampus after 1 h and 24 h. Furthermore, physostigmine reduced activated microglia and apoptosis relevant proteins and elevated the increased expression of TGF-beta1 and MFG-E8 after surgery stress. In conclusion, activation of autophagy may be essential in physostigmine-induced neuroprotection against surgery stress. PMID- 29790106 TI - Imaging Reporter Strategy to Monitor Gene Activation of Microglia Polarisation States under Stimulation. AB - Microglial cells as innate immune key players have a critical and unique role in neurodegenerative disorders. They strongly interact with their microenvironment in a complex manner and react to changes by switching their phenotype and functional activation states. In order to understand the development of brain diseases, it is imperative to elucidate up- or down-regulation of genes involved in microglia polarisation in time-profile by a simple-to-use strategy. Here, we present a new imaging strategy to follow promoter activity of genes involved in microglia polarisation. We lentivirally transduced BV-2 microglia cells in culture with constructs consisting of the induced nitric oxide synthase (iNOS), Fc gamma receptor III (Fcgr3) (both resembling the pro-inflammatory M1-like phenotype) or Chitinase-like 3 (Chil3/Ym1) (resembling the anti-inflammatory M2 like phenotype) promoters and stimulated transgenic cells with potent activators for pro- or anti-inflammatory response, such as lipopolysaccharide (LPS) + interferon gamma (IFN-gamma) or interleukin (IL)-4, respectively. Promoter activities upon polarisation phases were quantitatively assessed by the two imaging reporters Luc2 for bioluminescence and eGFP for fluorescence. PMID- 29790108 TI - The impact of dietary habits on the pathogenesis of rheumatoid arthritis: a case control study. AB - It has not been clear what kinds and how much nutrients could be harmful, preventive, or healthful for development of rheumatoid arthritis. This study aimed to determine the impact of dietary habits on the pathogenesis of rheumatoid arthritis. This case-control study was conducted on a total of 500 rheumatoid arthritis patients and 500 healthy controls refereed to three clinics of Shiraz University of Medical Sciences in 2015-2016. Convenience sampling was used for data collection in both case and control groups. An approved valid and reliable questionnaire including information about the intake of different kinds of beverages, and nutritious and non-nutritious diet was used. Data were analyzed by SPSS, version 20, using t test, chi-square and Multiple Logistic Regression model. The associations between rheumatoid arthritis development and variables including drinking 1-7 cups of coffee (OR = .44, CI .25-.76), >= 8 cups of coffee (OR = .50, CI .28-.90), full-fat milk (OR = 1.01, CI 1.003-1.03) per month, and intake of green tea (OR = .65, CI .45-.93) and solid oils (OR = 2.29, CI:1.57 3.34) were significant. Based on the findings, coffee consumption more than one cup per month and green tea might have preventive effects on developing rheumatoid arthritis. On the other hand, patients who consumed more full-fat milk per month and solid oil might be at risk of development of rheumatoid arthritis. Therefore, modification of diet based on these findings is suggested. Performing a cohort study to determine the causality effect of dietary habits and development and prevention of rheumatoid arthritis is recommended. PMID- 29790107 TI - The Role of Pharmacogenomics in Bipolar Disorder: Moving Towards Precision Medicine. AB - Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions. Pharmacogenetic studies in BD have been for the most part focused on lithium, but the complexity and variability of the response phenotype, together with the unclear mechanism of action of lithium, limited the power of these studies to identify robust biomarkers. Recent pharmacogenomic studies on lithium response have provided promising findings, suggesting that the integration of genome-wide investigations with deep phenotyping, in silico analyses and machine learning could lead us closer to personalized treatments for BD. Nevertheless, to date none of the genes suggested by pharmacogenetic studies on mood stabilizers have been included in any of the genetic tests approved by the Food and Drug Administration (FDA) for drug efficacy. On the other hand, genetic information has been included in drug labels to test for the safety of carbamazepine and valproate. In this review, we will outline available studies investigating the pharmacogenetics and pharmacogenomics of lithium and other mood stabilizers, with a specific focus on the limitations of these studies and potential strategies to overcome them. We will also discuss FDA-approved pharmacogenetic tests for treatments commonly used in the management of BD. PMID- 29790109 TI - Value of three-dimensional speckle tracking echocardiography to assess left ventricular function in hyperuricemia patients. AB - To assess the value of three-dimensional speckle tracking echocardiography (3D STE) in evaluating the left ventricular (LV) function in hyperuricemia patients. We enrolled 15 healthy controls and 40 hyperuricemia patients and collected and analyzed full-volume 3D STE images of the left ventricle in the apical four chamber heart view. Laboratory tests and 3D STE parameters, including left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume (SV), global longitudinal strain (GLS), and global circumferential strain (GCS), were compared between hyperuricemia patients and healthy controls. Hyperuricemia patients exhibited higher body mass index (24.70 +/- 2.9 vs. 21.83 +/- 2.4 kg/m2, p = 0.001), C reactive protein (5.82 +/- 9.4 vs. 1.12 +/- 1.8 g/L, p = 0.012), alanine transaminase (34.26 +/- 26.6 vs. 17.60 +/- 13.0 U/L, p = 0.011), aspartate transaminase (24.90 +/- 11.3 vs. 17.70 +/- 4.1 U/L, p = 0.001), blood urea nitrogen (5.11 +/- 1.6 vs. 4.18 +/- 0.6 mmol/L, p = 0.046), and serum creatinine (90.25 +/- 14.6 vs. 77.93 +/- 10.8 MUmol/L, p = 0.006) levels, as well as a lower estimated glomerular filtration rate (87.87 +/- 16.5 vs. 103.64 +/- 11.3 mL/min/1.73m2, p = 0.002). The 3D STE parameters reflecting LV function, including SV (54.71 +/- 9.6 vs. 61.92 +/- 14.4 mL, p = 0.024), GLS (- 20.51 +/- 4.0 vs. - 23.20 +/- 4.0%, p = 0.019), and GCS (- 31.30 +/- 5.0 vs. - 35.65 +/- 2.5%, p = 0.000), were significantly decreased in hyperuricemia patients. Furthermore, GCS was significantly correlated with the serum uric acid (sUA) level even after adjustment of confounding variables like age, body mass index, and serum creatinine. 3D STE is a novel technique for recognizing the early decline in LV function, with GLS and GCS serving as reliable indicators, in hyperuricemia patients. Moreover, the degree of decline in LV function may be correlated with the sUA level in hyperuricemia patients. PMID- 29790110 TI - Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample. AB - Hyperuricemia is not only a risk factor for gout but also an independent determinant of hypertension, diabetes, and chronic kidney diseases. Although the incidence of gout in Korean adults is increasing, epidemiologic studies on hyperuricemia in the general Korean population are limited. Thus, this study aimed at evaluating the prevalence of hyperuricemia and its associated factors among non-institutionalized Korean adults. The present study included 5548 participants (2403 men and 3145 women) aged >= 19 years from The Korea National Health and Nutrition Examination Survey. Based on the new 2016 census data, the age-standardized prevalence and mean uric acid level were calculated using the chi-square test and t test, respectively. A multivariate logistic regression analysis was performed to evaluate the risk factors associated with hyperuricemia. The age-standardized prevalence of hyperuricemia and mean uric acid level in the general Korean population was 11.4% (17.0% in men and 5.9% in women) and 5.1 mg/dL (5.83 mg/dL in men and 4.36 mg/dL in women), respectively. The prevalence of hyperuricemia was high in young Korean adults, and a U-shaped association was observed between hyperuricemia and age. While obesity, metabolic syndrome, renal impairment, and low-grade inflammation were positively associated with hyperuricemia in both sexes, alcohol consumption, education, and current smoking status had a positive association with hyperuricemia only in women. Hyperuricemia is prevalent in the young population in Korea, and special efforts are necessary to reduce the potential harmful effects of hyperuricemia on the health of adults, particularly the younger-generation adults, in Korea. PMID- 29790111 TI - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. AB - PURPOSE: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies. PMID- 29790113 TI - Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions. AB - There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods. Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes. These epitopes are involved in processes such as cell-cell recognition and are important as cancer biomarkers. Specific information that could be obtained from the intact N glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans. Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna. Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone. Graphical abstract ?. PMID- 29790114 TI - Ivabradine improved left ventricular function and pressure overload-induced cardiomyocyte apoptosis in a transverse aortic constriction mouse model. AB - This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva 10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson's trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice. PMID- 29790112 TI - An Automated, High-Throughput Method for Interpreting the Tandem Mass Spectra of Glycosaminoglycans. AB - The biological interactions between glycosaminoglycans (GAGs) and other biomolecules are heavily influenced by structural features of the glycan. The structure of GAGs can be assigned using tandem mass spectrometry (MS2), but analysis of these data, to date, requires manually interpretation, a slow process that presents a bottleneck to the broader deployment of this approach to solving biologically relevant problems. Automated interpretation remains a challenge, as GAG biosynthesis is not template-driven, and therefore, one cannot predict structures from genomic data, as is done with proteins. The lack of a structure database, a consequence of the non-template biosynthesis, requires a de novo approach to interpretation of the mass spectral data. We propose a model for rapid, high-throughput GAG analysis by using an approach in which candidate structures are scored for the likelihood that they would produce the features observed in the mass spectrum. To make this approach tractable, a genetic algorithm is used to greatly reduce the search-space of isomeric structures that are considered. The time required for analysis is significantly reduced compared to an approach in which every possible isomer is considered and scored. The model is coded in a software package using the MATLAB environment. This approach was tested on tandem mass spectrometry data for long-chain, moderately sulfated chondroitin sulfate oligomers that were derived from the proteoglycan bikunin. The bikunin data was previously interpreted manually. Our approach examines glycosidic fragments to localize SO3 modifications to specific residues and yields the same structures reported in literature, only much more quickly. Graphical Abstract ?. PMID- 29790115 TI - N-(2-hydroxyphenyl)acetamide and its gold nanoparticle conjugation prevent glycerol-induced acute kidney injury by attenuating inflammation and oxidative injury in mice. AB - The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury (AKI) in mice was investigated. NA-2 (50 mg/kg) and NA-2-AuNPs (30 mg/kg) were given to the animals for four days followed by 24-h water deprivation and injection of 50% glycerol (10 ml/kg im). The animals were sacrificed on the next day. Blood and kidneys were collected for biochemical investigations (urea and creatinine), histological studies (hematoxylin and eosin; and periodic acid Schiff staining), immunohistochemistry (actin and cyclooxygenase-2, Cox-2), and real-time RT-PCR (inducible nitric oxide synthase, iNOS; nuclear factor-kappaB p50, NFkappaB; hemeoxygenase-1, HO-1; and kidney injury molecule-1, Kim-1). NA-2 protected renal tubular necrosis and inflammation, though the result of NA-2 AuNPs was better than compound alone and it also exhibited the activity at far less dose. The test compound and its gold nano-formulation decreased the levels of serum urea and creatinine level in the treated animals. Both NA-2 and NA-2 AuNPs also conserved actin cytoskeleton, and lowered COX-2 protein expression. Moreover, the mRNA expressions of iNOS and NFkB p50 were down-regulated, and HO-1 and Kim-1 genes were up-regulated. We conclude that NA-2 and NA-2-AuNPs ameliorates kidney inflammation and injury in glycerol-induced AKI animal model via anti-oxidant and anti-inflammatory mechanisms which make it a suitable candidate for further studies. We believe that these findings will contribute in the understanding of the mechanism of action of paracetamol-like drugs and can be considered for clinical research for the prevention of AKI. PMID- 29790116 TI - Prediction of Shunt Dependency After Intracerebral Hemorrhage and Intraventricular Hemorrhage. AB - BACKGROUND: Spontaneous intracerebral hemorrhage is a disease with high morbidity and mortality. Extension of the hemorrhage into the ventricles is associated with the development of acute hydrocephalus and a poor outcome. Although it can be managed by external ventricular drainage (EVD), a subset of these patients require placement of permanent ventricular shunts. This study aimed to examine the factors on admission that can predict shunt dependency after EVD management. METHODS: Seventy-two patients who underwent EVD were included in this study. Seventeen of these patients underwent placement of a ventriculoperitoneal shunt. Variables analyzed included age, intraventricular hemorrhage (IVH) score, bicaudate index, acute hydrocephalus, initial Glasgow Coma Scale scores, and blood volume in each ventricle. RESULTS: In univariate analysis, IVH score (p = 0.020), bicaudate index (p < 0.001), blood volume in lateral ventricles (p = 0.025), blood volume in the fourth ventricle (p = 0.038), and the ratio of blood volume in lateral ventricles to that in third and fourth ventricles (p = 0.003) were significantly associated with persistent hydrocephalus. The best multiple logistic regression model included blood volume parameters and bicaudate index as predictors with the area under a receiver operating characteristic curve of 0.849. The variance inflation factor (VIF) showed that collinearity was not found among predictors. Patients diagnosed with acute hydrocephalus had less blood volume in the lateral ventricles (OR = 0.910) and had more blood volume in the third ventricle (OR = 3.174) and fourth ventricle (OR = 2.126). CONCLUSIONS: These findings may promote more aggressive monitoring and earlier interventions for persistent hydrocephalus after intraventricular hemorrhage in patients at risk. PMID- 29790119 TI - Dr. Margaret McCallum-Johnston: Canada's first female anesthesiologist. PMID- 29790117 TI - Regulatory roles of miR-155 and let-7b on the expression of inflammation-related genes in THP-1 cells: effects of fatty acids. AB - The main aim of this investigation was to study the regulatory roles of let-7b and miR-155-3p on the expression of inflammation-associated genes in monocytes, macrophages, and lipopolysaccharide (LPS)-activated macrophages (AcM). A second goal was to analyze the potential modulatory roles of different fatty acids, including oleic, palmitic, eicosapentaenoic (EPA), and docosahexaenoic (DHA), on the expression of these miRNAs in the three cell types. This hypothesis was tested in human acute monocytic leukemia cells (THP-1), which were differentiated into macrophages with 2-O-tetradecanoylphorbol-13-acetate (TPA) and further activated with LPS for 24 h. Monocytes, macrophages, and AcM were transfected with a negative control, or mimics for miR-155-3p and miR-let-7b-5p. The expression of both miRNAs and some proinflammatory genes was analyzed by qRT-PCR. Interestingly, let-7b mimic reduced the expression of IL6 and TNF in monocytes, and SERPINE1 expression in LPS-activated macrophages. However, IL6, TNF, and SERPINE1 were upregulated in macrophages by let-7b mimic. IL6 expression was higher in the three types of cells after transfecting with miR-155-3p mimic. Similarly, expression of SERPINE1 was increased by miR-155-3p mimic in monocytes and macrophages. However, TLR4 was downregulated by miR-155-3p in monocytes and macrophages. Regarding the effects of the different fatty acids, oleic acid increased the expression of let-7b in macrophages and AcM and also increased the expression of miR-155 in monocytes when compared with DHA but not when compared with non-treated cells. Overall, these results suggest anti- and proinflammatory roles of let-7b and miR-155-3p in THP-1 cells, respectively, although these outcomes are strongly dependent on the cell type. Noteworthy, oleic acid might exert beneficial anti-inflammatory effects in immune cells (i.e., non-activated and LPS-activated macrophages) by upregulating the expression of let-7b. PMID- 29790118 TI - Screening of acromegaly in adults with obstructive sleep apnea: is it worthwhile? PMID- 29790120 TI - Changes in the augmentation index and postoperative orthostatic intolerance in orthopedic surgery: a prospective cohort study. AB - BACKGROUND: Postoperative orthostatic intolerance (OI) can be a major obstacle to early ambulation and its determinants are poorly understood. We aimed to study postoperative changes in vascular tone and their potential association with OI in various orthopedic surgical settings. METHODS: In this prospective cohort study, 350 patients undergoing total joint arthroplasty under neuraxial anesthesia or spine surgery under general anesthesia were enrolled. We determined the augmentation index (AI) as a measure of vascular tone and studied symptoms of OI using a validated questionnaire at various postoperative time points. RESULTS: The AI was significantly reduced postoperatively (at spinal resolution in patients with neuraxial anesthesia or two hours postoperatively in general anesthesia) compared with baseline values in all procedures and did not subsequently return to baseline throughout the postoperative period in the majority of patients [252/335 (75.2%); P < 0.001]. The majority [260/342 (76.0%); P < 0.001] of patients had postoperative symptoms of OI. Nevertheless, no association was found between postoperative change in AI from baseline and postoperative symptoms of OI. CONCLUSIONS: A significantly prolonged decrease in AI and symptoms of OI are common after orthopedic surgery. Nevertheless, an association between the two measures was not observed. While compensatory mechanisms may limit the influence of an AI decrease on symptoms of OI, more research is needed to understand the contributing factors and aid in the identification of patients at risk of OI. PMID- 29790121 TI - When does reading dirty words impede picture processing? Taboo interference with verbal and manual responses. AB - Picture naming takes longer in the presence of socially inappropriate (taboo) distractor words compared with neutral distractor words. Previous studies have attributed this taboo interference effect to increased attentional capture by taboo words or verbal self-monitoring-that is, control processes scrutinizing verbal responses before articulation. In this study, we investigated the cause and locus of the taboo interference effect by contrasting three tasks that used the same target pictures, but systematically differed with respect to the processing stages involved: picture naming (requiring conceptual processing, lexical processing, and articulation), phoneme decision (requiring conceptual and lexical processing), and natural size decision (requiring conceptual processing only). We observed taboo interference in picture naming and phoneme decision. In size decision, taboo interference was not reliably observed under the same task conditions in which the effect arose in picture naming and phoneme decision, but it emerged when the difficulty of the size decision task was increased by visually degrading the target pictures. Overall, these results suggest that taboo interference cannot be exclusively attributed to verbal self-monitoring operating over articulatory responses. Instead, taboo interference appears to arise already prior to articulatory preparation, during lexical processing and-at least with sufficiently high task difficulty-during prelexical processing stages. PMID- 29790122 TI - Talking points: A modulating circle reduces listening effort without improving speech recognition. AB - Speech recognition is improved when the acoustic input is accompanied by visual cues provided by a talking face (Erber in Journal of Speech and Hearing Research, 12(2), 423-425 1969; Sumby & Pollack in The Journal of the Acoustical Society of America, 26(2), 212-215, 1954). One way that the visual signal facilitates speech recognition is by providing the listener with information about fine phonetic detail that complements information from the auditory signal. However, given that degraded face stimuli can still improve speech recognition accuracy (Munhall et al. in Perception & Psychophysics, 66(4), 574-583, 2004), and static or moving shapes can improve speech detection accuracy (Bernstein et al. in Speech Communication, 44(1/4), 5-18, 2004), aspects of the visual signal other than fine phonetic detail may also contribute to the perception of speech. In two experiments, we show that a modulating circle providing information about the onset, offset, and acoustic amplitude envelope of the speech does not improve recognition of spoken sentences (Experiment 1) or words (Experiment 2), but does reduce the effort necessary to recognize speech. These results suggest that although fine phonetic detail may be required for the visual signal to benefit speech recognition, low-level features of the visual signal may function to reduce the cognitive effort associated with processing speech. PMID- 29790123 TI - Language experience shapes relational knowledge of compound words. AB - Prior studies of noun-noun compound word processing have provided insight into the human capacity for conceptual combination (Gagne and Shoben Journal of Experimental Psychology: Learning, Memory, and Cognition, 23(1), 71 1997; Spalding, Gagne, Mullaly & Ji Linguistische Berichte Sonderheft, 17, 283-315 2010). These studies conclude that relational interpretations of compound words are proposed and appraised by the language system during online word recognition. However, little is known about how the capacity for creating new meanings from existing conceptual units develops within an individual mind. Though current theories imply that individual relational knowledge about the combinability of concepts develops as language experience accumulates, this hypothesis has not been previously tested experimentally. Here, we addressed this hypothesis in a task that assesses individual relational knowledge of English compound words. We report that greater experience with printed language shapes relational knowledge of compound words in two ways. Firstly, individuals with more experience with printed language were able to select a greater number of possible relational meanings for individual compound words. Secondly, individuals with greater experience with printed language were also more precise about which relational meaning was the most semantically plausible out of all possible meanings. Our results confirm that language experience affects an individual's ability to use relational knowledge in order to combine conceptual units. Our findings offer further support for the Lexical Quality Hypothesis (Perfetti, 2007), which states that lexical representations of words become simultaneously more flexible and precise as a result of repeated exposure to their orthographic forms in language usage. PMID- 29790124 TI - Colorectal Cancer: Why Does Side Matter? AB - Colorectal cancer (CRC) is a heterogeneous disease, and the search for clinical and molecular prognostic and predictive factors is thus necessary to better tailor each individual patient's management. Primary tumor location (PTL) seems to act as a master prognostic factor pooling different clinical, pathological, and molecular poor prognostic factors. In fact, right-sided (RS) CRC patients are more frequently female and elderly with microsatellite unstable, BRAF mutated, CpG island methylator phenotype (CIMP)-high, poorly differentiated tumors, compared to left-sided (LS) CRC patients. PTL does not seem to clearly influence disease-free survival (DFS) in localised colon cancer even though the opposite prognostic value of RS tumors on DFS depending on RAS/BRAF mutational status has been recently suggested in these patients. In metastatic CRC (mCRC), the poor prognosis associated with RS tumors is confirmed in the most recent publications in the era of double and triple chemotherapeutic regimens and targeted agents. Concerning the predictive value of PTL, in patients with RAS wild-type mCRC in the first-line setting, anti-epidermal growth factor receptor (EGFR) therapy combined with chemotherapy appears to be more effective than bevacizumab in LS CRC, while patients with RS CRC benefit less from anti-EGFR therapy, and intensive chemotherapy plus bevacizumab may be more appropriate but EGFR antibodies remain an option if objective response is needed. Due to the limitation of the current data (unplanned and retrospective analyses), these conclusions must be interpreted with caution. Clinical trials in RS CRC may be of interest to clarify what is the best treatment strategy in these patients. PMID- 29790125 TI - Management of major bleeding and outcomes in patients treated with direct oral anticoagulants: results from the START-Event registry. AB - The management of major bleeding in patients treated with direct oral anticoagulants (DOACs) is still not well established. START-Events, a branch of the START registry (Survey on anTicoagulated pAtients RegisTer) (NCT02219984), aims to describe the actual management of bleeding or recurrent thrombotic events in routine clinical practice. We here present the results of the management of bleeding patients. The START-Event registry is a prospective, observational, multicenter, international study. Baseline characteristics (demographic, clinical, risk factors) of patients, laboratory data at admission and during follow-up, site of bleeding, therapeutic strategies, and outcomes at the time of hospital discharge and after 6 months were recorded on a web-based case report form. Between January 2015 and December 2016, 117 patients with major bleeding events were enrolled. Non-valvular atrial fibrillation (NVAF) was the indication for treatment in 84% (62% males); 53 patients had intracranial bleeding (13 fatal), 42 had gastrointestinal bleeding (1 fatal), and 22 had bleeding in other sites. Therapeutic interventions for the management of bleeding were performed in 71% of patients. Therapeutic strategies with/without surgery or invasive procedures included: fluid replacement or red blood cells transfusion, prothrombin complex concentrates (3 or 4 factors), antifibrinolytic drugs, and the administration of idarucizumab. Creatinine, blood cell count, and PT/aPTT were the most frequent tests requested, while specific DOAC measurements were performed in 23% of patients. Mortality during hospitalization was 11.9%, at 6 month follow-up 15.5%. Our data confirm a high heterogeneity in the management of bleeding complications in patients treated with DOACs. PMID- 29790127 TI - Noninvasive auto-titrating ventilation (AVAPS-AE) versus average volume-assured pressure support (AVAPS) ventilation in hypercapnic respiratory failure patients: comment. PMID- 29790126 TI - Endocrinopathy-induced euvolemic hyponatremia. AB - Euvolemic hyponatremia results from either the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency. Furthermore, the criteria for diagnosis of SIADH entail the exclusion of hypothyroidism and hypoadrenalism. We aim to assess the yield of euvolemic hyponatremia workup focusing on underlying endocrinopathies in a real-world setting. A single-center retrospective study includes all patients diagnosed with euvolemic hyponatremia in a tertiary hospital between 1.1.2007 and 1.1.2013. Demographic, clinical, and laboratory data were collected from medical charts. Euvolemic hyponatremia was detected in 564 patients. Thyroid function was tested in 69% (391/564) and adrenal function was assessed in 29% (164/564) of cases. Endocrinopathy-induced euvolemic hyponatremia was diagnosed in nine (1.6%) patients: three patients were diagnosed with hypothyroidism-induced hyponatremia, three with adrenal insufficiency as an underlying cause, and three with central hypothyroidism and central hypoadrenalism. All nine had medical history and symptoms suggestive of endocrine deficiencies other than the hyponatremia, which resolved within 1-3 days after administration of hormone replacement therapy. Yield of performed workup for hypothyroidism and hypoadrenalism in euvolemic hyponatremia was low. However, in this real-world study, only a limited number of patients underwent a full ascertainment of hypoadrenalism and hypothyroidism, which was diagnosed only in patients with additional findings supportive of these endocrinopathies; a higher rate of undiagnosed endocrinopathies cannot be ruled out. As both hypoadrenalism and hypothyroidism are easily treatable, potentially life-threatening conditions, there are insufficient data to change current recommendation for their universal evaluation in patients with euvolemic hyponatremia. PMID- 29790128 TI - Evidence That the Length of Bile Loop Determines Serum Bile Acid Concentration and Glycemic Control After Bariatric Surgery. AB - BACKGROUND: Bariatric surgery contributes to the improvement in glucose metabolism that may be related to a postoperative increase in serum bile acids (BAs). Three commonly used types of bariatric procedures, laparoscopic sleeve gastrectomy (LSG) (without creation of a bile loop), Roux-en-Y gastric bypass (RYGB), and omega-loop gastric bypass (OLGB) (with creation of shorter 100-150 cm and longer 200-280 cm bile loops, respectively), differ in their effects on glycemic control. The aim of the study was to compare the effects of various bariatric procedures on serum BA concentration and glucose homeostasis. METHODS: Serum BAs in 26 obese patients were determined by liquid chromatography-mass spectrometry prior to bariatric surgery, as well as 4 days and 3 months thereafter. RESULTS: Four days after the surgery, serum concentrations of BAs in LSG and OLGB groups were similar as prior to the procedure, and a slight decrease in serum BAs was observed in the RYGB group. Serum BA level in the LSG group remained unchanged also at 3 months after the surgery, whereas a significant 0.5- and 3-fold increase in this parameter was noted in the RYGB and OLGB groups, respectively. Serum concentration of BAs correlated positively with the length of the bile loop (R = 0.47, p < 0.05). CONCLUSION: The evident improvement of glycemic control observed 3 months after OLGB might be associated with a postoperative increase in serum BAs, resulting from their better absorption from the longer bile loop. However, the changes in serum BAs probably had little or no impact on insulin sensitivity improvement at 4 days post-surgery. PMID- 29790129 TI - Duodenum Exclusion Alone Is Sufficient to Improve Glucose Metabolism in STZ Induced Diabetes Rats. AB - BACKGROUND: Several studies have found that metabolic surgery can significantly improve glucose homeostasis; however, the intrinsic mechanisms remain unclear. Accumulating evidence suggests that duodenal bypass plays a crucial role in the treatment of type 2 diabetes mellitus (T2DM). Here, we aimed to evaluate the effect of duodenal reflux on glucose metabolism in T2DM. METHODS: A high-fat diet and low-dose streptozotocin (STZ) administration were used to induce T2DM in male rats, which were assigned to three experimental groups: sham operation (SO; n = 10), new duodenal-jejunal bypass (NDJB; n = 10), and new duodenal-jejunal bypass with a tube (NDJBT; n = 10). Weight, food intake, oral glucose tolerance test (OGTT) results, glucagon-like peptide 1 (GLP-1) levels, and histopathology were assessed before or after surgery. Plain abdominal radiography was performed 1 week after the operation. RESULTS: Plain abdominal radiography indicated the occurrence of contrast agent reflux into the duodenum. The body weight and food intake in all three groups did not significantly differ before and after surgery. The NDJB and particularly the NDJBT groups exhibited better glucose tolerance, lower fasting blood glucose (FBG) levels, lower area under the curves for OGTT (AUCOGTT) values, and higher GLP-1 levels, as compared with the sham group postoperatively. The villus height and crypt depth were both shorter in the biliopancreatic limb after NDJBT, as compared with those after SO and NDJB. CONCLUSIONS: Thus, exclusion of the duodenum alone and tube placement can effectively prevent duodenal reflux and improve glucose homeostasis, which further suggests that the duodenum plays an important role in T2DM. PMID- 29790130 TI - An Analysis of Mid-Term Complications, Weight Loss, and Type 2 Diabetes Resolution of Stomach Intestinal Pylorus-Sparing Surgery (SIPS) Versus Roux-En-Y Gastric Bypass (RYGB) with Three-Year Follow-Up. AB - BACKGROUND: For many years, the Roux-en-Y Gastric Bypass (RYGB) was considered a good balance of complications and weight loss. According to several short-term studies, single anastomosis duodenal switch or stomach intestinal pylorus sparing surgery (SIPS) offers similar weight loss to RYGB with fewer complications and better diabetes resolution. No one has substantiated mid-term complication and nutritional differences between these two procedures. This paper seeks to compare complication and nutritional outcomes between RYGB and SIPS. METHODS: A retrospective analysis of 798 patients who either had SIPS or RYGB from 2010 to 2016. Complications were gathered for each patient. Nutritional outcomes were measured for each group at 1, 2, and 3 years. Regression analysis was applied to interpolate each patient's weight at 3, 6, 9, 12, 18, 24, and 36 months. These were then compared with t tests, Fisher's exact tests, and chi-squared tests. RESULTS: RYGB and SIPS have statistically similar weight loss at 3, 6, 9, 12, and 36 months. They statistically differ at 18 and 24 months. At 36 months, there is a trend for weight loss difference. There were only statistical differences in nutritional outcomes between the two procedures with calcium at 1 and 3 years and vitamin D at 1 year. There were statistically significantly more long-term class IIIb-V complications, class I-IIIa complications, reoperations, ulcers, small bowel obstructions, nausea, and vomiting with the RYGB than the SIPS. CONCLUSION: With comparable weight loss and nutritional outcomes, SIPS has fewer short- and long-term complications than RYGB and better type 2 diabetes resolution rates. PMID- 29790131 TI - Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review. AB - OBJECTIVE: Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. METHODS: Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. RESULTS: Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. CONCLUSIONS: Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis. PMID- 29790133 TI - [Spiritual Care for Patients and Their Families in the Intensive Care Unit]. AB - To date, most of the literature in Taiwan on clinical spiritual care has focused either on improving the spiritual well-being of patients or on developing assessment tools suitable for use with end-stage cancer patients. Few articles have discussed spiritual care in the context of intensive care unit (ICU) patients and their family members. When ICU patients face life-threatening and complex physiological problems, spiritual care plays an important role in disease recovery and adaptation and impacts the satisfaction and medical decision-making of critical patients and their family members. This article describes the synergy model and spiritual care guidelines for ICU patients and their families. Furthermore, this article supplements two recent interventional studies that targeted ICU patients in intensive care unit with direct and easily understood instructions for self-implementation of the two dimensions, vertical and horizontal, of spiritual well-being. The author hopes to provide a practical reference for implementing spiritual care with ICU patients and their families in clinical practice. PMID- 29790132 TI - Updates on the research and development of absorbable metals for biomedical applications. AB - Absorbable metals, metals that corrode in physiological environment, constitute a new class of biomaterials intended for temporary medical implant applications. The introduction of these metals has shifted the established paradigm of metal implants from preventing corrosion to its direct application. Interest toward absorbable metals has been growing in the past decade. This is proved by the rapid increase in scientific publication, progressive development of standards, and launching the first commercial products. Iron, magnesium, zinc, and their alloys are the current three absorbable metals families. Magnesium-based metals are the most progressing family with a large data set obtained from both basic and translational research. Iron-based metals are still facing a major challenge of low in vivo corrosion rate despite the significant efforts that have been put to overcome its weakness. Zinc-based metals are the new alternative absorbable metals with moderate corrosion rates that fall between those of iron and magnesium. This manuscript provides a brief review on the latest progress in the research and development of absorbable metals, the most important findings, the remaining challenges, and the perspective on the future direction. PMID- 29790134 TI - [HIV Stigma and Spiritual Care in People Living With HIV]. AB - HIV infection has been a manageable and chronic illness in Taiwan since the highly active antiretroviral therapy was introduced in 1997. HIV infection is a stigmatized disease due to its perceived association with risky behaviors. HIV often carries a negative image, and people living with HIV(PLWH) face discrimination on multiple fronts. Internalized HIV stigma impacts the spiritual health of people living with HIV in terms of increased levels of shame, self blame, fear of disclosing HIV status, and isolation and decreased value and connections with God, others, the environment, and the self. Nursing professionals provide holistic care for all people living with HIV and value their lives in order to achieve the harmony of body, mind, and spirit. This article describes the stigma that is currently associated with HIV and how stigma related discrimination affects the spiritual health of PLWH and then proposes how to reduce discrimination and stigma in order to improve the spiritual health of PLWH through appropriate spiritual care. Reducing HIV stigma and promoting spiritual well-being will enable Taiwan to achieve the 'Three Zeros' of zero discrimination, zero infection, and zero death advocated by the Joint United Nations Programme on HIV/AIDS for ending the AIDS epidemic in 2030. PMID- 29790135 TI - [Spiritual Care of Patients With Depression]. AB - Spiritual care is a component of holistic care. Patients with depression often experience body-mind-spirit health problems and may suffer from spiritual crises, particularly during the acute stage of a diseases, due to low self-esteem, negative attitudes toward life goals, daily life issues, and beliefs caused by physical, psychological, and occupational dysfunctions. Nonetheless, psychical care is the main treatment for patients with depression. This paper focuses on patients with depression and addresses the concepts of spiritual needs and spiritual care, identifying the factors that influence spiritual needs, the essentials of spiritual intervention, and the health effects of spiritual intervention outcomes on patients with depression. Courses that teach practical spiritual interventions are recommended for nurses. These courses should address topics such as individual approaches, building trusting relationships, setting diverse goals for spiritual interventions based on disease stage, and spiritual interventions involving the body-mind-spiritual aspects for patients with depression. PMID- 29790136 TI - [Mutual Support Beyond Suffering and Mortality-Spiritual Care for Families of Terminal Cancer Patients]. AB - With the progression of cancer and the approach of death in terminal cancer patients, the suffering of the family members of patients increases drastically, often leading into a difficult spiritual journey. The needs for spiritual care in this population generally consist of: 1. Empathy: Bearing the psychological stress due to the sharing of physical pain with the patients; 2. Powerlessness: Regretting not having the power to turn the tide; 3. Loneliness: Becoming exhausted due to facing heavy physical workloads alone; 4. Break down: Feeling hopeless in the face of the myriad challenges of care; 5. Despair: Feeling perplexed by the prospects of a desperate future; 6. Sorrow: Feeling bitter due to the realization that the disease is incurable and to being reluctant to acknowledge the parting. The spiritual needs of family members may be met by evaluating the needs for and resistance to spiritual care, followed by the use of religious and non-religious companions and the application of listening and empathy approaches in order to elicit positive thoughts and the values of love, forgiveness, and reconciliation. In strengthening their personal beliefs, family members may find connectedness with god, humanity, and objects; may see hope in life; and may find the meaning of suffering in order to further seek and find inner peace, accomplish themselves, and eventually achieve spiritual sublimation. PMID- 29790137 TI - [Diabetic Foot Neuropathy and Related Factors in Patients With Type 2 Diabetes Mellitus]. AB - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) face a higher risk of diabetic foot neuropathy, which increases the risk of death. The early detection of factors that influence diabetic neuropathy reduces the risk of foot lesions, including foot ulcerations, lower extremity amputation, and mortality. PURPOSE: To explore the demographic, disease-characteristic, health-literacy, and foot self-care-behavior factors that affect diabetic foot neuropathy in patients with T2DM. METHODS: A case-control study design was employed in which cases (Michigan Neuropathy Screening Instrument, MNSI) >= 2 were matched to controls based on age and gender in a medical center. A total of 114 patients diagnosed with T2DM in a medical center were recruited as participants. Data were collected using a structured questionnaire. The collected data were analyzed using Fisher's exact test, Mann-Whitney U test, and logistic regression. RESULTS: The results of multiple logistic regression showed that glycated hemoglobin (B = 1.696, p = .041) and communication and critical health literacy (B = -0.082, p = .034) were significant factors of diabetic foot neuropathy. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study suggest that nurses should assess the health literacy of patients with T2DM before providing health education and should develop a specific foot-care intervention for individuals with poor glycemic control. PMID- 29790139 TI - [The Process of Healing Child Physical Abuse: Sprouting and Twining]. AB - BACKGROUND: Child physical abuse impacts the physical and psychological health of survivors. Healing child abuse is an essential process that helps survivors reorganize the meaning of the trauma and pursue a normal life. Considering the trauma of child physical abuse within the social context allows the experiences of individual survivors to be reflected in their process of healing. PURPOSE: To explore the social interaction and construction process of healing experienced by survivors of child physical abuse. METHODS: A qualitative research design using grounded theory was applied. Purposive and theoretical sampling was used to recruit survivors of childhood physical abuse who had experienced healing. Semi structured, in-depth interviews were used and data were analyzed using open, axial, and selective coding. RESULTS: The process of healing child physical abuse in this study was a process of sprouting and twining. Three core categories emerged: thriving, relationships, and ethics. The healing process was analogous to a seed growing in poor soil, sprouting out from the ground, and striving to live by seeking support. The survivors constantly established interactive relationships with their selves and with others and struggled to keep family bonds grounded and growing within the frame of ethics. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The healing process of sprouting and twining for child physical abuse survivors in Taiwan integrates thriving, relationships, and ethics. Professionals working with child-physical-abuse survivors must recognize conflicts in ethics. Strategies should be developed to assist survivors to cope with the impact of childhood trauma in order to facilitate the healing process. PMID- 29790138 TI - [The Relationship Between Fatigue and Uncertainty in Patients With Liver Cirrhosis]. AB - BACKGROUND: Cirrhosis is a chronic, progressive, and currently incurable disease. Cirrhotic patients often experience uncertainty due to poor control of symptoms and disease recurrence. Although fatigue is a common symptom in patients with liver cirrhosis, this symptom is often ignored by healthcare professionals due to the lack of efficacious treatment options. Improper management of fatigue may trigger greater uncertainty and affect adaptation success. PURPOSE: To explore the relationship between fatigue and uncertainty and the factors that respectively relate to these two concepts in liver cirrhosis patients. METHODS: A cross-sectional, correlational design and convenience sampling were used to recruit 76 liver cirrhotic inpatients from one hospital. Three structured questionnaires, including the Personal Demographic Questionnaire, Brief Fatigue Inventory-Taiwan Form, and Mishel's Uncertainty in Illness Scale, were used for data collection. RESULTS: (1) The participants suffered from fatigue at a moderate or higher level, with an average score of 5.39 +/- 2.34, which affected their daily activities and greatly impacted their recreational activities. Factors that were found to be associated with fatigue included disease severity, albumin level, total bilirubin level, ascites, and the degree to which fatigue affected the performance of daily activities. (2) Uncertainty was found to be at a moderate or higher level, with an average score of 71.81 +/- 10.67. Level of fatigue, the degree to which fatigue affected the performance of daily activities, disease severity, and albumin level were found to relate significantly to level of uncertainty. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Fatigue and uncertainty are prevalent and distressing experiences for patients with liver cirrhosis. A comprehensive assessment and broad-based approach to nursing interventions are necessary in order to alleviate fatigue and uncertainty effectively. PMID- 29790140 TI - [The Relationship Between Quality of Life and Psychological and Behavioral Factors in Patients With Heart Failure Following Cardiac Resynchronization Therapy]. AB - BACKGROUND: While cardiac resynchronization therapy improves the quality of life of patients with heart failure, some psychological and behavioral factors still affect the quality of life of these patients. However, information on the factors that affect the quality of life of these patients is limited. PURPOSE: To describe the quality of life and investigate the relationship between quality of life and behavioral and psychological factors such as depression, smoking, drinking, water and sodium restrictions, exercise, and adherence in patients with chronic heart failure following cardiac resynchronization therapy. METHODS: This cross-sectional study was conducted using the Morisky Medication Adherence Scale, Minnesota Living With Heart Failure Questionnaire, and Cardiac Depression Scale. A convenience sample of 141 patients with heart failure following cardiac resynchronization therapy were recruited from a tertiary academic hospital in Chengdu. RESULTS: The mean overall score of the Minnesota Living With Heart Failure Questionnaire was 30.89 (out of a total possible score of 105). Water restrictions, sodium restrictions, depression, and exercise were all shown to significantly predict quality of life among the participants. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This paper describes the quality of life and defines the behavioral factors that affect the quality of life of patients with heart failure following cardiac resynchronization therapy. The findings suggest that nurses should manage and conduct health education for patients in order to improve their quality of life. PMID- 29790141 TI - [Using TRM to Enhance the Accuracy of Ventilator-Associated Pneumonia Preventive Measures Implemented by Neonatal Intensive Care Unit Medical Staffs]. AB - BACKGROUND & PROBLEMS: Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the neonatal intensive care unit (NICU). The average VAP infection density was 4.70/00 in our unit between June and August 2015. The results of a status survey indicated that in-service education lacked specialization, leading to inadequate awareness among staffs regarding the proper care of newborns with VAP and a lack of related care guides. This, in turn, resulted in inconsistencies in care measures for newborns with VAP. PURPOSE: To improve the accuracy of implementation of preventive measures for VAP among medical staffs and reduce the density of VAP infections in the NICU. RESOLUTIONS: Conduct a literature search and adopt medical team resources management methods; establish effective team communication; establish monitoring mechanisms and incentives; establish mandatory in-service specialization education contents and a VAP preventive care guide exclusively for newborns as a reference for medical staffs during care execution; install additional equipment and aids and set reminders to ensure the implementation of VAP preventive measures. RESULTS: The accuracy rate of preventive measure execution by medical staffs improved from 70.1% to 97.9% and the VAP infection density in the NICU decreased from 4.70/00 to 0.520/00. CONCLUSIONS: Team integration effectively improved the accuracy of implementation of VAP-prevention measures, reduced the density of VAP infections, enhanced quality of care, and ensured that newborns received care that was more in line with specialization needs. PMID- 29790142 TI - [Application of Care Bundles to Reduce Medical-Device-Related Pressure Injury (MDRPI) Incidence in a Coronary Care Unit]. AB - BACKGROUND & PROBLEMS: Pressure injuries increase the cost of medical care and prolong hospitalization. The incidence of pressure injury at the target coronary care unit (CCU) from January to August 2016 was 1.1%, which was significantly higher than the 0.4% defined in the 2015 Taiwan Clinical Performance Indicators (TCPI) system. Medical device related pressure injury (MDRPI) accounted for 73.1% of the pressure injuries (incidence: 0.8%). The main causes of the high incidence of MDRPI were: (1) inadequate decompression dressing and restraint equipment, (2) incomplete implementation of prevention interventions in the CCU, (3) inadequate knowledge of MDRPI prevention among nurses, (4) deficient standards for preventing MDRPI, (5) ineffective MDRPI-related education, and (6) insufficient auditing frequencies. PURPOSE: To reduce the incidence of MDRPI in the target CCU to 0.4% or less. RESOLUTION: Promote a seed-teacher system and a care bundle that "increased skin tolerance, decompression, medical dressing, change, and removal" using education, the adoption of PE-foam binding gloves, and regular audits. RESULTS: The incidence of MDRPI was reduced from 0.8% to 0.3% between October 2016 and April 2017 and further reduced to 0.1% during the maintenance phase between May and July 2017. CONCLUSIONS: The results indicate that the improvement program effectively reduced the incidence of MDRPI and thus increased the quality of nursing care. Therefore, the use of a care bundles should be promoted in intensive care units. PMID- 29790143 TI - [Managing the Adverse Effects Related to Immune Checkpoint Inhibitors]. AB - Immune checkpoint inhibitors (ICIs) have become the new posterchild of cancer treatment in recent years largely due to their impressive clinical efficacy. Drugs targeting cytotoxic T- lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) antibodies, e.g., ipilimumab (Yervoy(r)), pembrolizumab (Keytruda(r)), and nivolumab (Opdivo(r)), reinvigorate cytotoxic T cells to kill cancer cells in patients. Despite the impressive clinical benefits, ICIs may induce immune-related adverse events (irAE) of the skin, gastrointestinal tract, liver, endocrine, and lung with a wide spectrum of severity. Rare but severe irAEs of critical organs such as the heart and central nervous system have also been reported. Clinical practitioners must recognize the early signs and symptoms of irAE as well as related management strategies. PMID- 29790146 TI - RE: The tolerability of Potassium Citrate Tablet in patients with intolerance to Potassium Citrate Powder form. PMID- 29790144 TI - [Prone Position and Nursing Care]. AB - Acute respiratory distress syndrome (ARDS) is a life-threatening disease, as acute inflammation in the lungs typically leads to hypoxia and symptoms of dyspnea. The treatment modalities of ARDS include mechanical ventilation, corticosteroid, extracorporeal membranous oxygenation, inhaled nitrogen oxide, and the prone position. Among these, the prone position is supported by evidence showing significantly reduced mortality in patients that adopt this modality. Lying in the prone position reduces atelectatic lung volumes by recruitment of dependent parts and facilitates normal regulation of alveolar ventilation, giving better-matched ventilation perfusion and, thus, improved oxygenation. Lying in the prone position should be initiated as early as possible and may be implemented when there is limited improvement after 12-24 hours under mechanical ventilation and when the PaO2/FiO2 ratio is less than 150 mmHg. However, the prone position may not be appropriate for patients with increased intracranial pressure, hemodynamic instability, an open abdominal wound, or pregnancy. Prior to setting a patient in the prone position, fixation of tubings should be affirmed, and all tubings should be reexamined after each adjustment in position in order to ensure that they are free of twists and function well. In addition, caution should be given to the skin at pressure points to avoid pressure sores and foam dressings may be applied in advance for protection. This article summarizes the pathophysiology of ARDS, the principle of applying the prone position, and related indications, complications, and nursing care in order to give nurses more confidence in caring for patients using the prone position. PMID- 29790145 TI - [Nursing Experience of Using Mirror Visual Feedback for a Schizophrenia Patient With Visual Hallucinations]. AB - The aim of this paper was to describe the nursing application of mirror visual feedback in a patient suffering from long-term visual hallucinations. The intervention period was from May 15th to October 19th, 2015. Using the five facets of psychiatric nursing assessment, several health problems were observed, including disturbed sensory perceptions (prominent visual hallucinations) and poor self-care (e.g. limited abilities to self-bathe and put on clothing). Furthermore, "caregiver role strain" due to the related intense care burden was noted. After building up a therapeutic interpersonal relationship, the technique of brain plasticity and mirror visual feedback were performed using multiple nursing care methods in order to help the patient suppress her visual hallucinations by enhancing a different visual stimulus. We also taught her how to cope with visual hallucinations in a proper manner. The frequency and content of visual hallucinations were recorded to evaluate the effects of management. The therapeutic plan was formulated together with the patient in order to boost her self-confidence, and a behavior contract was implemented in order to improve her personal hygiene. In addition, psychoeducation on disease-related topics was provided to the patient's family, and they were encouraged to attend relevant therapeutic activities. As a result, her family became less passive and negative and more engaged in and positive about her future. The crisis of "caregiver role strain" was successfully resolved. The current experience is hoped to serve as a model for enhancing communication and cooperation between family and staff in similar medical settings. PMID- 29790147 TI - Sensitivity and specificity of ex vivo dermatoscopy: a case series. AB - BACKGROUND: Sensitivity and specificity of ex vivo dermatoscopy (EVD) for malignancy detection of skin tumors is unknown. We sought to assess whether the use of EVD could be a useful adjunct to histopathological diagnosis of pigmented skin tumors, including cases where complete clinical information is inadequate or missing. MATERIALS AND METHODS: EVD was performed on 195 excised, formalin-fixed pigmented skin tumors. RESULTS: Of 183 eligible lesions, 104 (56.8%) were melanocytic and 79 (43.2%) nonmelanocytic. Overall, 54 (29.5%) were malignant: 10 melanomas, 39 basal cell carcinomas, and five squamous cell carcinomas. Ex vivo images were devoid of red color. The following colors were seen: light and dark brown, grey, blue, black, and white. All structures typical for pigmented melanocytic and nonmelanocytic lesions were observed. In malignant nonmelanocytic lesions, diagnostic accuracy and sensitivity for malignant/benign decision was not better when combining visual assessment and EVD but diagnostic specificity improved by 3.0%. For melanoma, combined diagnostics improved diagnostic accuracy, sensitivity, and specificity for 9.6, 30.0, and 7.5%, respectively. CONCLUSION: For dermatopathologists, EVD offers increased specificity for all categories of tumors and increased diagnostic accuracy, sensitivity, and specificity for melanoma. With EVD view, the dermatopathologist can instantly find areas of interest, thus minimizing the possibility for missing a malignant lesion. PMID- 29790148 TI - Prospective pilot study of cerebral near infrared spectroscopy monitoring during pre-hospital anaesthesia. AB - BACKROUND: Near-infrared spectroscopy (NIRS) provides a non-invasive measure of cerebral tissue oxygenation. The literature on application of this method in pre hospital setting is limited. The aims of this study were to determine the feasibility of cerebral NIRS during pre-hospital anaesthesia and to quantify the changes in front lobe regional oxygen saturation (rSO2 ) during the pre-hospital phase. METHODS: NIRS monitoring (Nonin SenSmart X-100) of front lobe regional oxygen saturation (rSO2) was initiated before induction of anaesthesia in 31 adult patients and continued until hospital arrival. The median age of the patients was 55 years (IQR [range] 43-63 [20-84]), and 20 (65%) of the patients were male. The indications for pre-hospital anaesthesia were neurological reasons (29%), intoxication (23%), traumatic brain injury (23%) and successful resuscitation from cardiac arrest (16%). RESULTS: The NIRS monitoring was successful in 29 of 31 cases (94%; 95% CI: 78-99). One patient could not be monitored due to poor probe-skin contact, and 1 patient had poor contact with 1 hemisphere. Monitoring was performed for a total of 1335 minutes and was successful in both hemispheres 95% (95% CI: 94-96) of the time. The median lowest rSO2 was 8% (IQR [range] 2-13 [0-30]) below baseline, and median peak rSO2 was 7% (IQR [range] 2-11 [0-34]) above the baseline. Changes in rSO2 without accompanying changes in vital signs were observed. CONCLUSION: NIRS is feasible during pre-hospital anaesthesia and substantial changes were observed in some patients. It provides data beyond the standard monitoring used in the pre hospital setting. PMID- 29790150 TI - The emerging role of awake videolaryngoscopy in airway management. PMID- 29790149 TI - Survival after secondary cytoreductive surgery and chemotherapy compared with chemotherapy alone for first recurrence in patients with platinum-sensitive epithelial ovarian cancer and no residuals after primary treatment. A registry based study. AB - INTRODUCTION: To investigate whether secondary cytoreductive surgery and platinum based chemotherapy improved survival among patients with recurrent, platinum sensitive epithelial ovarian cancer compared with those who received platinum based chemotherapy alone, and to identify possible predictors for selection to secondary cytoreductive surgery. MATERIAL AND METHODS: We included 397 patients who had a primary diagnosis of FIGO stage I-IV epithelial ovarian cancer recorded in the Cancer Registry of Norway between 1 January 2002 and 31 December 2012, received primary surgery with no residuals followed by platinum-based chemotherapy, had first recurrence six or more months after completion of primary platinum-based chemotherapy, and received secondary treatment with either secondary cytoreductive surgery and platinum-based chemotherapy (secondary cytoreductive surgery+platinum-based chemotherapy group) or platinum-based chemotherapy alone (platinum-based chemotherapy group). Outcomes were progression free survival to second recurrence or death and overall survival. Hazard ratios were estimated using multivariable Cox regression. RESULTS: There were 75 patients in the secondary cytoreductive surgery+platinum-based chemotherapy group in whom complete resection was achieved for 60 (80%), and 322 patients in the platinum-based chemotherapy group. Both progression-free survival (hazard ratio 0.45, 95% confidence interval 0.32-0.62) and overall survival (hazard ratio 0.50, 95% confidence interval 0.32-0.70) were improved in the secondary cytoreductive surgery+platinum-based chemotherapy compared with the platinum-based chemotherapy group. A survival benefit was only seen in patients with no residuals at secondary cytoreductive surgery. CONCLUSIONS: In selected epithelial ovarian cancer patients with no residuals after primary surgery and a recurrent, platinum sensitive tumor, the complete resection of recurrent tumor at secondary cytoreductive surgery improves progression-free survival and overall survival. Our results suggest that a long treatment-free interval and non-disseminated lesions (three or fewer lesions) on radiological images could be useful predictors for complete resection at secondary cytoreductive surgery. PMID- 29790151 TI - Irreversible modifications of receptor tyrosine kinases. AB - Each group of the 56 receptor tyrosine kinases (RTK) binds with one or more soluble growth factors and coordinates a vast array of cellular functions. These outcomes are tightly regulated by inducible post-translational events, such as tyrosine phosphorylation, ubiquitination, ectodomain shedding, and regulated intramembrane proteolysis. Because of the delicate balance required for appropriate RTK function, cells may become pathogenic upon dysregulation of RTKs themselves or their post-translational covalent modifications. For example, reduced ectodomain shedding and decreased ubiquitination of the cytoplasmic region, both of which enhance growth factor signals, characterize malignant cells. Whereas receptor phosphorylation and ubiquitination are reversible, proteolytic cleavage events are irreversible, and either modification might alter the subcellular localization of RTKs. Herein, we focus on ectodomain shedding by metalloproteinases (including ADAM family proteases), cleavage within the membrane or cytoplasmic regions of RTKs (by gamma-secretases and caspases, respectively), and complete receptor proteolysis in lysosomes and proteasomes. Roles of irreversible modifications in RTK signaling, pathogenesis, and pharmacology are highlighted. PMID- 29790152 TI - Machine learning algorithms for accurate differential diagnosis of lymphocytosis based on cell population data. PMID- 29790153 TI - Centenarians' End-of-Life Thoughts and Plans: Is Their Social Network on the Same Page? AB - OBJECTIVES: To explore how centenarians think about and plan for the end of life (EOL) and to what extent their primary contacts (proxy informants) are aware of these thoughts. DESIGN: Population-based study with semistructured in-person interviews. SETTING: Defined geographical region approximately 60 km around Heidelberg, Germany. PARTICIPANTS: Subsample drawn from the larger study of centenarians (N = 78) with data on centenarians' EOL thoughts from the centenarian and the proxy informant. MEASUREMENTS: Centenarians reported on their thoughts about the EOL, perception of the EOL as threatening, longing for death, engagement in any EOL planning, and type of EOL plan (will, living will, healthcare surrogate) in place. Proxy respondents answered the same set of questions based on what they thought the centenarians' perspective was. RESULTS: In nearly half of cases, proxies misjudged whether the centenarian thought about EOL. Although only few centenarians perceived the EOL as threatening, and approximately one-quarter reported longing for death, proxies overestimated centenarians' reports on the former and underestimated the latter. Proxies reported more centenarian EOL planning than centenarians themselves. CONCLUSION: Even though enrolled proxies were mostly persons very close to the centenarian, many of them did not seem to be well informed about the centenarians' thoughts and plans regarding the EOL, suggesting a lack of communication between centenarians and social network members in this respect. Healthcare professionals should be aware that, even for very old adults approaching the end of their lives, discussions about EOL and EOL planning may need to be actively encouraged and supported. PMID- 29790154 TI - Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer-specific survival. AB - BACKGROUND: Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women. METHODS: Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER) positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation. RESULTS: Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78.5 per cent) were identified as having ER-positive disease; of these, 10 087 (53.9 per cent) had surgery and 8643 (46.1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69.4 and 89.9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival. CONCLUSION: BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit. PMID- 29790155 TI - Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt. AB - OBJECTIVE: The goal of this study was to determine whether combat veterans who have made a suicide attempt postdeployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. METHODS: Demographic and clinical parameters of suicide attempters and non-attempters were assessed. Blood samples were assayed for dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). RESULTS: Suicide attempters had higher Scale for Suicidal Ideation and Montgomery-Asberg Depression Rating Scale (MADRS)-suicidal thoughts item scores in comparison with non-attempters. There was a trend toward higher MADRS scores in the suicide attempter group compared with non-attempters. Suicide attempters had significantly lower levels of DHEA and DHEAS compared with non-attempters. Scale for Suicidal Ideation scores in all study participants combined negatively correlate with DHEA and DHEAS levels. DHEAS levels negatively correlate with Scale for Suicidal Ideation scores in suicide non-attempters but not in suicide attempters. DHEA/DHEAS ratios positively correlate with total adolescence aggression scores, total adulthood aggression scores, and total aggression scale scores in suicide attempters but not in suicide non-attempters. CONCLUSION: There are psychobiological differences between combat veterans with or without a history of suicidal behaviour. PMID- 29790156 TI - Revisiting the impact of red cell storage duration on adverse outcomes after transfusion. PMID- 29790157 TI - Pallister-Killian syndrome: Review of fetal phenotype. AB - Pallister-Killian syndrome is a multi-system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS. PMID- 29790158 TI - Change in Mallampati class during labor: Hypertensive versus normotensive parturients. AB - BACKGROUND: Mallampati class has been shown to increase during labor. There are no prospective studies evaluating airway changes in hypertensive parturients during labor. The aim of our study was to observe the frequency of change in Mallampati class during labor in hypertensive compared to normotensive parturients. METHODS: In this prospective observational cohort study, 60 parturients were enrolled and divided into two groups of 30 each: hypertensive parturients and normotensive parturients. The Mallampati class was evaluated in each parturient at two points; during early labor (cervical dilation 1-3 cm and regular contractions) taken as T1 and at 20 minutes after delivery taken as T2. The change in Mallampati class from T1 to T2 was compared between the two groups. Post-stratification chi-square test was applied and P value <.05 was considered as significant. RESULTS: The change in Mallampati class was significantly more frequent in hypertensive group as compared to normotensive group [80% (24/30) vs 46.7% (14/30); P = .002]. Overall, an increase in Mallampati class during labor was found with statistically significant difference between the hypertensive and normotensive group [80% (24/30) vs 42.9% (12/28); P = .004]. The risk of increase in Mallampati class was 2 times higher in hypertensive women as compared to normotensive 2.44; 95% CI: 1.19 to 5.02]. CONCLUSION: Mallampati class showed 2 fold increase in hypertensive compared to normotensive parturients during labor; requiring additional caution during airway management. PMID- 29790159 TI - Development of a new analgesic index using nasal photoplethysmography. AB - Although surrogate measures to quantify pain intensity have been commercialised, there is a need to develop a new index with improved accuracy. The aim of this study was to develop a new analgesic index using nasal photoplethysmography data. The specially designed sensor was placed between the columella and the nasal septum to acquire nasal photoplethysmography in surgical patients. Nasal photoplethysmography and Surgical Pleth Index(r) (GE Healthcare) data were obtained for 14 min both in the absence (pre-operatively) or presence (postoperatively) of pain in a group of surgical patients, each patient acting as their own control. Various dynamic photoplethysmography variables were extracted to quantify pain intensity; the most accurate index was selected using logistic regression as a classifier. The area under the curve of the receiver-operating characteristic curve was measured to evaluate the accuracy of final model predictions. In total, 12,012 heart beats from 89 patients were used to develop a new Nasal Photoplethysmography Index for analgesic depth quantification. The two variable model (a combination of diastolic peak point variation and heart beat interval variation) was most accurate in discriminating between the presence and absence of pain (numerical rating scale (NRS) >= 3). The accuracy and area under the curve of the receiver-operating characteristic curve for the Nasal Photoplethysmography Index were 75.3% and 0.8018, respectively, and 64.8% and 0.7034, respectively, for the Surgical Pleth Index. The Nasal Photoplethysmography Index clearly distinguished pain (NRS >= 3) in awake surgical patients with postoperative pain. The Nasal Photoplethysmography Index performed better than the Surgical Pleth Index. Further validation studies are needed to evaluate its feasibility to quantify pain intensity during general anaesthesia. PMID- 29790160 TI - I follow, therefore I lead: A longitudinal study of leader and follower identity and leadership in the marines. AB - It is acknowledged that identity plays an important role in a person's leadership development. To date, however, there has been little consideration of the possibility - suggested by the social identity perspective - that individuals who identify as followers may be especially likely to emerge as leaders. We test this possibility in a longitudinal sample of recruit commandos in the Royal Marines. Recruits rated their identification with leader and follower roles five times over the course of their 32-week training programme. Recruits' leadership and followership were evaluated by their commanders, and their leadership was assessed by their peers. Analysis indicated that while recruits who identified as leaders received higher leadership ratings from their commanders, recruits who identified - and were perceived - as followers emerged as leaders for their peers. These findings suggest that follower and leader identities underpin different aspects of leadership and that these are differentially recognized by others. PMID- 29790161 TI - Time after seawater transfer influences immune cell abundance and responses to SAV3 infection in Atlantic salmon. AB - Pancreas disease (PD) caused by salmonid alphavirus (SAV) severely affects salmonid aquaculture during the seawater phase. To characterize immune cells in target tissues for SAV infection, heart, pancreas and pyloric caeca were analysed from two groups of fish adapted to seawater for 2 and 9 weeks. The sections were scored for the relative abundance of cells expressing MHC class II, IgM, CD3, CD8 or neutrophil/granulocyte markers using immuno-histochemical techniques. In general, necrosis of tissue was more severe in fish infected at 2 weeks post seawater transfer (wpt) compared with those infected at 9 wpt. At 9 wpt, there were higher numbers of MHC II+ cells in heart, pancreas and pyloric caeca, IgM+ cells in heart and pancreas, and CD3+ cells in pancreas compared to those infected at 2 wpt. The majority of the immune cells infiltrating PD-affected tissues were MHC II+ and CD3+ cells suggesting that antigen-presenting cells and T lymphocytes are the main types of immune cells responding to SAV infection. All the investigated cell types were also observed in pyloric caeca of infected fish, suggesting that this tissue may play a role in the immune response to SAV. PMID- 29790162 TI - Getting What We Pay For: How Do Risk-Based Payments to Medicare Advantage Plans Compare with Alternative Measures of Beneficiary Health Risk? AB - OBJECTIVE: To estimate the relative health risk of Medicare Advantage (MA) beneficiaries compared to those in Traditional Medicare (TM). DATA SOURCES/STUDY SETTING: Medicare claims and enrollment records for the sample of beneficiaries enrolled in Part D between 2008 and 2015. STUDY DESIGN: We assigned therapeutic classes to Medicare beneficiaries based on their prescription drug utilization. We then regressed nondrug health spending for TM beneficiaries in 2015 on demographic and therapeutic class identifiers for 2014 and used coefficients from this regression to predict relative risk of both MA and TM beneficiaries. PRINCIPAL FINDINGS: Based on prescription drug utilization data, beneficiaries enrolled in MA in 2015 had 6.9 percent lower health risk than beneficiaries in TM, but differences based on coded diagnoses suggested MA beneficiaries were 6.2 percent higher risk. The relative health risk based on drug usage of MA beneficiaries compared to those in TM increased by 3.4 p.p. from 2008 to 2015, while the relative risk using diagnoses increased 9.8 p.p. CONCLUSIONS: Our results add to a growing body of evidence suggesting MA receives favorable, or, at worst, neutral selection. If MA beneficiaries are no healthier and no sicker than similar beneficiaries in TM, then payments to MA plans exceed what is warranted based on their health status. PMID- 29790163 TI - Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis. AB - BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions. PMID- 29790165 TI - IgG1+ B-cell immunity predates IgE responses in epicutaneous sensitization to foods. AB - BACKGROUND: The generation of IgE-mediated food allergy in humans is silent and only diagnosed upon manifestation of clinical symptoms. While experimental models have been used to investigate some mechanisms of allergic sensitization, the generation of humoral immunity and memory remains to be elucidated. Here, we defined the evolution of allergen-specific B-cell responses during epicutaneous sensitization to foods. METHODS: Wild-type and genetic knockout animals, and drug or antibody strategies for cell depletion and immunoglobulin signaling blockade were used to investigate epicutaneous sensitization and disease progression; we analyzed allergen-specific germinal centers and IgG1+ memory B cells by flow cytometry, evaluated humoral responses, and determined clinical reactivity (anaphylaxis). RESULTS: Epicutaneous sensitization caused microscopic skin damage, inflammation, and recruitment of activated dendritic cells to the draining lymph nodes. This process generated allergen-specific IgG1+ germinal center B cells, serum IgG1, and anaphylaxis that was mediated by the alternative pathway. Whether we used peanut and/or ovalbumin from the egg white for sensitization, the allergen-specific IgG1+ memory compartment predominantly exhibited an immature, pro-germinal center phenotype (PDL-2- CD80- CD35+ CD73+ ). Subsequent subclinical exposures to the allergen induced IgE+ germinal center B cells, serum IgE, and likely activated the classical pathway of anaphylaxis. CONCLUSIONS: Our data demonstrate that IgG1+ B-cell immunity against food allergens in epicutaneous sensitization precedes the generation of IgE responses. Therefore, the assessment of allergen-specific cellular and humoral IgG1+ immunity may help to identify individuals at risk of developing IgE-mediated food allergy and hence provide a window for therapeutic interventions. PMID- 29790167 TI - Beware of memes in the interpretation of your results - lessons from gene disrupted mice in fertilization research. AB - For decades, researchers in the fertilization field reported various candidate factors involved in sperm-egg interaction through experiments using enzyme inhibitors and/or antibodies. However, almost all of these factors have been shown to be nonessential by gene disruption experiments. Recently, attention has focused on the low reproducibility of papers in many research fields. In this Review, I retrospectively revisit how fertilization factors were misinterpreted and led to wrong hypotheses in relation to the reportedly low reproducibility of scientific papers. PMID- 29790166 TI - Physical Therapy as the First Point of Care to Treat Low Back Pain: An Instrumental Variables Approach to Estimate Impact on Opioid Prescription, Health Care Utilization, and Costs. AB - OBJECTIVE: To compare differences in opioid prescription, health care utilization, and costs among patients with low back pain (LBP) who saw a physical therapist (PT) at the first point of care, at any time during the episode or not at all. DATA SOURCES: Commercial health insurance claims data, 2009-2013. STUDY DESIGN: Retrospective analyses using two-stage residual inclusion instrumental variable models to estimate rates for opioid prescriptions, imaging services, emergency department visits, hospitalization, and health care costs. DATA EXTRACTION: Patients aged 18-64 years with a new primary diagnosis of LBP, living in the northwest United States, were observed over a 1-year period. PRINCIPAL FINDINGS: Compared to patients who saw a PT later or never, patients who saw a PT first had lower probability of having an opioid prescription (89.4 percent), any advanced imaging services (27.9 percent), and an Emergency Department visit (14.7 percent), yet 19.3 percent higher probability of hospitalization (all p < .001). These patients also had significantly lower out-of-pocket costs, and costs appeared to shift away from outpatient and pharmacy toward provider settings. CONCLUSIONS: When LBP patients saw a PT first, there was lower utilization of high-cost medical services as well as lower opioid use, and cost shifts reflecting the change in utilization. PMID- 29790164 TI - Purinergic receptor stimulation induces calcium oscillations and smooth muscle contraction in small pulmonary veins. AB - KEY POINTS: We investigated the excitation-contraction coupling mechanisms in small pulmonary veins (SPVs) in rat precision-cut lung slices. We found that SPVs contract strongly and reversibly in response to extracellular ATP and other vasoconstrictors, including angiotensin-II and endothelin-1. ATP-induced vasoconstriction in SPVs was associated with the stimulation of purinergic P2Y2 receptors in vascular smooth muscle cell, activation of phospholipase C-beta and the generation of intracellular Ca2+ oscillations mediated by cyclic Ca2+ release events via the inositol 1,4,5-trisphosphate receptor. Active constriction of SPVs may play an important role in the development of pulmonary hypertension and pulmonary oedema. ABSTRACT: The small pulmonary veins (SPVs) may play a role in the development of pulmonary hypertension and pulmonary oedema via active changes in SPV diameter, mediated by vascular smooth muscle cell (VSMC) contraction. However, the excitation-contraction coupling mechanisms during vasoconstrictor stimulation remain poorly understood in these veins. We used rat precision-cut lung slices and phase-contrast and confocal microscopy to investigate dynamic changes in SPV cross-sectional luminal area and intracellular Ca2+ signalling in their VSMCs. We found that the SPV (~150 MUm in diameter) contract strongly in response to extracellular ATP and other vasoconstrictors, including angiotensin II and endothelin-1. ATP-induced SPV contraction was fast, concentration dependent, completely reversible upon ATP washout, and inhibited by purinergic receptor antagonists suramin and AR-C118925 but not by MRS2179. Immunofluorescence showed purinergic P2Y2 receptors expressed in SPV VSMCs. ATP induced SPV contraction was inhibited by phospholipase Cbeta inhibitor U73122 and accompanied by intracellular Ca2+ oscillations in the VSMCs. These Ca2+ oscillations and SPV contraction were inhibited by the inositol 1,4,5 trisphosphate receptor inhibitor 2-APB but not by ryanodine. The results of the present study suggest that ATP-induced vasoconstriction in SPVs is associated with the activation of purinergic P2Y2 receptors in VSMCs and the generation of Ca2+ oscillations. PMID- 29790168 TI - Periodontitis and placental growth factor in oral fluids are early pregnancy predictors of gestational diabetes mellitus. AB - BACKGROUND: Gestational diabetes mellitus (GDM) affects around 7% to 10% of all pregnancies. Early detection of predisposition to GDM is the first step in developing efficacious preventive treatment. The objective of the present study was to establish the utility of placental proteins presents in oral fluids (gingival crevicular fluid [GCF] and saliva), and periodontal disease status as early pregnancy predictors of GDM. METHODS: A nested case control within a prospective cohort was conducted. Pregnant systemically healthy women, aged between 18 and 40 years at 11 to 14 weeks gestation were included. Samples of oral fluids were collected and a complete maternal/obstetric and periodontal history was obtained. The concentration of placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay in a nested case control sample of the prospective cohort. Multiple logistic regression models assessed the association. The evaluation of the diagnostic accuracy of the biomarkers was performed through receiver operating characteristic (ROC) curves by calculating the area under the curve (AUC). RESULTS: There were recruited 212 pregnant women at 11 to 14 weeks of pregnancy, of these, 14 women (i.e., 6.6%) developed GDM, and displayed significant greater bleeding on probing (BOP) [P = 0.0003]; periodontal probing depth (PD) [P = 0.0028]; clinical attachment level (AL) [P = 0.0008] and periodontal inflamed surface area (PISA) [P = 0.0001]. Similarly, initial glycemia and GCF-PlGF concentrations were significantly greater in women with GDM [P = 0.0012, and P = 0.0019, respectively]. When data were subjected to ROC curve analysis, the combination of initial glycemia and GCF-PlGF concentration delivered an area under the ROC curve of 0.897. Multiple logistic regression analyses demonstrate an association between glycemia (OR 1.21, 95% confidence interval [CI] 1.06 to 1.38; P = 0.005) and GCF-PlGF concentrations in women who developed GDM (OR 1.68, CI 1.05 to 2.68 P = 0.03). CONCLUSIONS: Within the limitations of the present study, the results support that first trimester maternal glycemia combined with GCF-PlGF concentrations could be a surrogate biomarker for the future development of GDM in pre-symptomatic women. PMID- 29790169 TI - MET in gastric cancer with liver metastasis: The relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis. AB - BACKGROUND AND OBJECTIVES: Although MET amplification/overexpression was observed in a subset of gastric cancer (GC) patients, the relationship between MET amplification/overexpression in primary GC and liver metastasis was unclear. METHODS: GC samples and matched liver metastases (N = 47) were analyzed by fluorescence/silver in-situ hybridization (FISH/SISH) and by immunohistochemistry for MET amplification and MET expression, respectively. MET-copy number (CN) and Met expression data from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA STAD, N = 356) were also analyzed. RESULTS: Significant overlap existed between MET amplification and Met expression in both primary stomach tumors (P = 0.013) and liver metastasis (P = 0.001). In TCGA-STAD, MET-CN (>=4 copies) and MET expression were also positively correlated (r = 0.761; P = 0.017). Comparative analysis revealed a strong association between MET expression and MET amplification (85% concurrence) in primary stomach tumors and matched liver metastasis. MET status in synchronous liver metastasis (N = 36) was correlated with primary stomach tumors. However, a significant correlation between primary tumors and liver metastases was not observed in patients with metachronous liver metastasis. Survival analyses revealed that both MET amplification and MET overexpression were prognostic of poor outcomes. CONCLUSIONS: MET amplification and Met overexpression were positively correlated in GC. MET status should be re evaluated in GC patients with liver metastasis, especially for metachronous metastasis. PMID- 29790170 TI - Calculation of breast volumes from mammogram: Comparison of four separate equations relative to mastectomy specimen volumes. AB - BACKGROUND AND OBJECTIVES: Accurately assessing breast volume (BV) relative to the volume of breast tissue to be removed could help objectively determine the optimal surgical candidates for breast conserving surgery. The objective of this study was to determine the optimal mammography-based method of BV estimation. METHODS: Mammography data was obtained for patients who underwent mastectomy for breast cancer from 2005 to 2015. This data was used to calculate BV using four previously published equations. Results were compared to mastectomy specimen volumes calculated from specimen weights and breast density. Five practitioners then independently assessed reproducibility and ease of use. RESULTS: Complete mammographic measurements were available for 65 breasts from 45 patients. Median age was 58 years (range 19-82). Mammographic breast density scores were available for 62 breasts. Of the 65 mastectomies performed, 16 (36%) were simple mastectomies. The equation BV = 1/3piRcc Rmlo Hmlo most closely approximated actual breast specimen volumes (R = 0.89, P < 0.0001). Internal correlation of calculated BV was excellent among all practitioners (lowest Pearson R = 0.963). CONCLUSIONS: Breast volumes can be reliably estimated utilizing measurements from a preoperative mammogram. This low-cost method of volumetric analysis can be employed to guide surgical decision making in treatment of patients with invasive breast cancer. PMID- 29790171 TI - Individual variation, population-specific behaviours and stochastic processes shape marine migration phenologies. AB - The phenology of long-distance migrations can influence individual fitness, moderate population dynamics and regulate the availability of ecosystem services to other trophic levels. Phenology varies within and among populations, and can be influenced by conditions individuals experience both prior to departure and encounter en route. Assessing how intrinsic and extrinsic factors (e.g., individual physical condition vs. environmental conditions) interact to influence variation in migratory phenologies across ecological scales is often limited due to logistical constraints associated with tracking large numbers of individuals from multiple populations simultaneously. We used two natural tags, DNA and otolith microstructure analysis, to estimate the relative influence of individual traits (life-history strategy, body size at departure and growth during migration), population-specific behaviours and interannual variability on the phenology of marine migrations in juvenile sockeye salmon Oncorhynchus nerka. We show that the timing and duration of juvenile sockeye salmon migrations were correlated with both life-history strategy and body size, while migration duration was also correlated with departure timing and growth rates during migration. Even after accounting for the effect of individual traits, several populations exhibited distinct migration phenologies. Finally, we observed substantial interannual and residual variation, suggesting stochastic environmental conditions moderate the influence of carry-over effects that develop prior to departure, as well as population-specific strategies. Migratory phenologies are shaped by complex interactions between drivers acting at multiple ecological and temporal scales. Given evidence that intraspecific diversity can stabilize ecological systems, conservation efforts should seek to maintain migratory variation among populations and preserve locally adapted phenotypes; however, variation within populations, which may buffer systems from environmental stochasticity, should also be regularly assessed and preserved. PMID- 29790173 TI - Allergic contact dermatitis caused by octylisothiazolinone in a leather sofa. PMID- 29790172 TI - Cell remodeling and subtilase gene expression in the actinorhizal plant Discaria trinervis highlight host orchestration of intercellular Frankia colonization. AB - Nitrogen-fixing filamentous Frankia colonize the root tissues of its actinorhizal host Discaria trinervis via an exclusively intercellular pathway. Here we present studies aimed at uncovering mechanisms associated with this little-researched mode of root entry, and in particular the extent to which the host plant is an active partner during this process. Detailed characterization of the expression patterns of infection-associated actinorhizal host genes has provided valuable tools to identify intercellular infection sites, thus allowing in vivo confocal microscopic studies of the early stages of Frankia colonization. The subtilisin like serine protease gene Dt12, as well as its Casuarina glauca homolog Cg12, are specifically expressed at sites of Frankia intercellular colonization of D. trinervis outer root tissues. This is accompanied by nucleo-cytoplasmic reorganization in the adjacent host cells and major remodeling of the intercellular apoplastic compartment. These findings lead us to propose that the actinorhizal host plays a major role in modifying both the size and composition of the intercellular apoplast in order to accommodate the filamentous microsymbiont. The implications of these findings are discussed in the light of the analogies that can be made with the orchestrating role of host legumes during intracellular root hair colonization by nitrogen-fixing rhizobia. PMID- 29790174 TI - An update of NIH research funding of AAPM members from 1985 to 2017. PMID- 29790175 TI - Mechanisms of cell regulation - proteolysis, the big surprise. AB - Precise regulation of cellular processes is essential for life. Regarding proteins, many regulatory mechanisms were explored over the years, such as posttranslational modifications (e.g., phosphorylation), enzyme activation or inhibition by small molecules, and modulation of protein-protein interactions. Complete removal of a protein via proteolysis as a regulatory mechanism, however, was denied for a long time, mainly due to economical considerations. Scientists could not believe that a protein which is synthesized at the expense of a lot of energy could be destroyed again. Here, we discuss the landmark discoveries and the use of yeast as a eukaryotic model organism that finally paved the way for our current understanding of proteolysis as an essential regulatory principle in the cell. PMID- 29790176 TI - Tau filaments in neurodegenerative diseases. AB - The ordered assembly of Tau protein into abnormal filamentous inclusions is a defining characteristic of many human neurodegenerative diseases. Thirty years ago, we reported that Tau is an integral component of the intraneuronal filaments of Alzheimer's disease. All six brain Tau isoforms make up those filaments. Twenty years ago, we and others showed that mutations in MAPT, the Tau gene, cause familial forms of frontotemporal dementia, thus proving that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. More recently, we showed that high-resolution structures of Tau filaments from human brain can be determined by electron cryo-microscopy. These filaments may form the seeds that underlie the prion-like properties of aggregated tau. PMID- 29790177 TI - MRI-based EMVI positivity predicts systemic recurrence in rectal cancer patients with a good tumor response to chemoradiotherapy followed by surgery. AB - BACKGROUND: This study aimed to determine the prognostic value of baseline magnetic resonance imaging-based extramural vascular invasion status (EMVI) among rectal cancer patients with a good tumor response to standard chemoradiotherapy followed by surgery. METHODS: A total of 359 patients with ypT0-2/N0 disease from The Yonsei Multicenter Colorectal Cancer Electronic Database were retrospectively included between January 2000 and December 2014. Magnetic resonance images and medical records were reviewed to investigate risk factors for tumor recurrence. RESULTS: When we compared patients without and with EMVI, significant differences were observed in the 5-year disease-free survival rate (DFS) (80.8% vs 57.8%, P = 0.005) and in the 5-year systemic recurrence-free survival rate (SRFS) (86.9% vs 64.3%, P = 0.007). In the multivariate analysis, both mrEMVI and APR independently predicted overall DFS (APR; HR 2.088, 95% CI: 1.082-4.031, P = 0.028, mrEMVI; HR: 2.729, 95% CI: 1.230-6.058, P = 0.014). mrEMVI was only independent prognostic factor for systemic recurrence with statistical significance (HR: 3.321, 95% CI: 1.185-9.309, P = 0.022). CONCLUSION: Even in rectal cancer patients with a good response to chemoradiotherapy followed by curative surgery, extramural vascular invasion and APR may predict poor disease free survival outcomes. Intensified treatment strategy should be considered. PMID- 29790180 TI - Very late sensitization to parabens induced by repeated applications of an anaesthetic therapeutic plaster to non-damaged skin. PMID- 29790179 TI - Merkel cell carcinoma: Clinical outcome and prognostic factors in 351 patients. AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. AIM: To describe clinical outcome and prognostic factors of MCC patients in two expert-centers. METHOD: Patients with histologically confirmed MCC in 1990-2014 were included. Data on patient, tumor characteristics and treatment were retrospectively collected. RESULTS: A total of 351 Patients were evaluated, 153 (44%) males, median age 74 years (range 28-94). Median follow up time was 28 months (IQR 13-58). Median primary tumor size was 17 mm (range 2 135). At time of diagnosis 112 (32%) patients had lymph node metastases. The cohorts' 5-year overall survival (OS) was 58%. Using a competing risk analysis the 5-year relapse and MCC related death was 42% and 22%. Adjuvant radiation therapy (XRT) was associated with reduced recurrence (SDH 0.54; CI 0.3-0.9). Nodal involvement (SDH 2.7; CI 1.1-6.6) and the male gender were associated with higher MCC related death (SDH 3.1; CI 1.2-7.9) CONCLUSION: In a large cohort a low MCC related death, in the presence of a low OS was seen. This indicates that a significant number of MCC patients die due to other causes than MCC. Adjuvant XRT was associated with relapse. Male gender and nodal metastasis were associated with MCC related death. PMID- 29790178 TI - Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer. AB - BACKGROUND: There were limited data available for a head-to-head comparison of the identification rate and survival between the combined method of indocyanine green fluorescence and blue dye versus the traditional blue dye alone method for sentinel lymph node (SLN) biopsy. METHODS: From January 2013 to December 2015, 523 eligible breast cancer patients were included in this nonrandomized prospective analysis. The identification rates, the number of SLNs identified, and the disease-free survival (DFS) between the two mapping methods were compared. RESULTS: The identification rate of SLNs was significantly higher with the combined method than that with the blue dye alone method (99.2% vs 93.3%, respectively; P < 0.001). The average number of SLNs identified per patient in the combined method group was 3.7 +/- 2.4, which was more than that in the blue dye alone group (3.2 +/- 1.6; P = 0.004). With a median follow-up of 29 months, 0.5% patients in the combined group, and 1.3% patients in the blue dye group had axillary recurrences. The DFS between the two groups showed no significant difference (P = 0.161). CONCLUSION: The combined method achieved a higher identification rate and lower rate of axillary recurrence compared to the blue dye alone method. PMID- 29790181 TI - Spatial Semantics, Cognition, and Their Interaction: A Comparative Study of Spatial Categorization in English and Korean. AB - This study has two goals. First, we present much-needed empirical linguistic data and systematic analyses on the spatial semantic systems in English and Korean, two languages that have been extensively compared to date in the debate on spatial language and spatial cognition. We conduct our linguistic investigation comprehensively, encompassing the domains of tight- and loose-fit as well as containment and support relations. The current analysis reveals both cross linguistic commonalities and differences: From a common set of spatial features, each language highlights a subset of those features for its principal categorization, and those primary features are importantly different between English and Korean: English speakers categorize events predominantly by containment and support relations (and do so with prepositions), whereas Korean speakers categorize them by tight-fit and loose-fit relations (and do so with verbs), with a further distinction of containment and support within the loose fit relation. The analysis also shows that the tight-fit domain is more cross linguistically diverse in categorization than is the loose-fit domain. Second, we test the language data against the nonlinguistic categorization results reported in Choi and Hattrup (2012). The results show a remarkable degree of convergence between the patterns predicted from the current linguistic analysis and those found in C&H's nonlinguistic study and thus provide empirical and strong evidence for an influence of language on nonlinguistic spatial cognition. At the same time, the study reveals areas where the two systems closely interact with each other as well as those where one is independent from the other. Taking both parts of the study together, we identify the specific roles that language and spatial perception/cognition play in spatial categorization. PMID- 29790182 TI - Effect of chronic toluene exposure on heart rhythm parameters. AB - BACKGROUND: Toluene is used extensively in various industrial processes, and an increasing number of workers are getting exposed to its vapor. Cardiac abnormalities that have been reported in association with toluene exposure (in toxic doses) are atrioventricular conduction abnormalities, sinus bradycardia, ventricular tachycardia, recurrent myocardial infarction, dilated cardiomyopathy, and coronary vasospasm. HYPOTHESIS: We aimed to investigate the effects of chronic toluene exposure on cardiac rhythm. METHODS: In this study, 40 workers in the polishing industry with more than 3 months of exposure to a mixture of organic solvents including toluene and 38 control subjects working in other fields who were matched by age, sex, smoking, habits, and living accommodation were investigated. Twelve-lead surface electrocardiogram and 24-hour Holter recordings were performed to determine QRS duration, PR duration (P and R wave interval on electrocardiograms), P wave dispersion, corrected QT dispersion, and heart rate variability parameters. RESULTS: The maximum heart rate was significantly lower in the toluene-exposed group compared to the control group (130.5 +/- 15.1 vs 138.6 +/- 16.0, P = 0.02). Corrected low frequency (cLF) and cLF/corrected high frequency (cHF) were also significantly lower in toluene exposed group (43.6 +/- 7.2 vs 50.7 +/- 10.5, P = 0.01 and 1.4 +/- 0.4 vs 2.2 +/- 1.0, P < 0.01, respectively). Mean cHF, root-mean-square successive difference, and standard deviation of all five-minute NN interval means values were significantly higher in the toluene-exposed group (32.8 +/- 8.1 vs 25.4 +/- 8.2, P <= 0.01; 74.0 +/- 46.1 vs 60.3 +/- 59.4, P = 0.02; and 149.5 +/- 77.0 vs 108.9 +/- 43.2, P = 0.01, respectively). CONCLUSIONS: This study implies that chronic toluene exposure disturbs cardiac autonomy, particularly by suppressing sympathetic activity, and parasympathetic suppression also occurs with increased exposure duration. We also demonstrated that chronic toluene exposure was not associated with major cardiac arrhythmias and rhythm conduction system disorders. PMID- 29790183 TI - Fasting Inhibits the Recruitment of Kinesin-1 to Lipid Droplets and Stalls Hepatic Triglyceride Secretion. PMID- 29790185 TI - A combined epicardial implantation and subsequent extraction strategy in pacemaker device infection in pacemaker-dependent patients. AB - INTRODUCTION: Treatment infections is challenging in pacemaker (PM) dependent patients. We proposed a novel implantation strategy for this group of patients. METHODS: Patients who were PM dependent and were admitted with a PM infection received a combined procedure of left ventricular (LV) epicardial implantation of a PM lead and subsequent extraction of the infected system. No temporary pacing wire was used and the PM generator was placed in the left flank. RESULTS: Between 2012 and 2015 we treated 16 patients who were PM dependent and with a PM infection. The majority of patients were male (81% [13/16]) and the median age was 71 years (50-91). The cause of infection was valvular endocarditis in 38% (6/16), lead infection in 25% (4/16), and isolated pocket infection in 38% (6/16). All patients underwent epicardial implantation of a LV lead (1084T bipolar lead; St. Jude Medical Myodex, St. Paul, MN, USA) and extraction of the infected device. There was no occurrence of periprocedural mortality and no postprocedural tamponades. There was one complication in the form of a hemorrhage at the infected device extraction site. In the median follow-up period of 17 months there were four of 16 deaths, none of which were attributable to epicardial LV implantation. LV-lead threshold was 1.1V (+/-0.7V) upon implantation that increased to 1.2V (+/-0.6V) at 0.4-ms pulse duration. There were no reinfections of the epicardial lead or device. CONCLUSION: Epicardial left ventricle PM implantation and subsequent extraction of an infected PM in PM dependent patients is feasible and safe with good long-term outcome. PMID- 29790184 TI - Human Leukocyte Antigen F Locus Adjacent Transcript 10 Overexpression Disturbs WISP1 Protein and mRNA Expression to Promote Hepatocellular Carcinoma Progression. AB - Recently, studies on transcriptome-proteome relationships have revealed mRNA/protein expression discordance for certain genes and speculated that protein posttranslational modification (PTM) may be involved. However, there is currently no evidence to support this hypothesis. Wnt-induced secreted protein-1 (WISP1) is the downstream target gene of beta-catenin and plays an important role in tumorigenesis and progression, but the expression and role of WISP1 in different tumor types are controversial. Here, we first confirmed that WISP1 protein expression was significantly down-regulated in hepatocellular carcinoma (HCC) tissue and could be an independent predictor of poor prognosis for patients with HCC. In vivo and in vitro evidence was provided that WISP1 can suppress HCC cell proliferation. Further studies have found that low WISP1 protein expression was related to expression of human leukocyte antigen F locus adjacent transcript 10 (FAT10), a specific ubiquitin-like protein with both degradation and stabilization functions, which plays an important role in PTM. FAT10 overexpression facilitated WISP1 degradation by FAT10ylation to decrease WISP1 protein expression, thus promoting HCC proliferation. Interestingly, we found and demonstrated that FAT10 overexpression could result in WISP1 protein/mRNA expression discordance, with protein expression decreasing while mRNA expression increased. The underlying mechanism is that FAT10 exerts substrate stabilization and degradation functions simultaneously, while FAT10 overexpression promotes WISP1 mRNA expression by stabilizing beta-catenin and directly degrades WISP1 protein. Conclusion: Our study demonstrated that overexpression of FAT10 results in expression discordance between WISP1 protein and mRNA, thereby promoting HCC progression by down-regulating WISP1 protein expression. PMID- 29790186 TI - Predicting events in clinical trials using two time-to-event outcomes. AB - In clinical trials with time-to-event outcomes, it is of interest to predict when a prespecified number of events can be reached. Interim analysis is conducted to estimate the underlying survival function. When another correlated time-to-event endpoint is available, both outcome variables can be used to improve estimation efficiency. In this paper, we propose to use the convolution of two time-to-event variables to estimate the survival function of interest. Propositions and examples are provided based on exponential models that accommodate possible change points. We further propose a new estimation equation about the expected time that exploits the relationship of two endpoints. Simulations and the analysis of real data show that the proposed methods with bivariate information yield significant improvement in prediction over that of the univariate method. PMID- 29790187 TI - Eosinophilic annular erythema treated with dupilumab. AB - Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cases reported in the English literature, 7 of which are in children. We present a case of recurrent eosinophilic annular erythema in an adolescent that was successfully treated with dupilumab, an interleukin-4 receptor alpha antagonist. PMID- 29790188 TI - Coagulation Failure in Patients With Acute-on-Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio. AB - Balanced hemostasis with hypocoagulable and hypercoagulable features may occur in acute-on-chronic liver failure (ACLF). The characteristics and prognostic impact of the coagulation profile in ACLF are unknown. Consecutive patients with ACLF (n = 36) and acute decompensation (AD; n = 24) were included. Blood samples for thromboelastometry (TE) were obtained at admission and 72 hours thereafter. The coagulation profile was evaluated in patients with and without ACLF and in those with and without systemic inflammatory response syndrome. The impact of the coagulation profile on transfusion requirements, bleeding events, and short-term survival was assessed. At admission, patients with ACLF showed more hypocoagulable characteristics compared to AD subjects, with prolonged time to initial fibrin formation and clot formation time and decreased maximum clot firmness and alpha-angle values. TE parameters worsened at 72 hours in ACLF but improved in patients with AD. Prevalence of a hypocoagulable profile (three or more TE parameters outside range) was significantly higher in patients with ACLF either at admission (61% versus 29% in AD; P = 0.03) or during follow-up. Hypocoagulability correlated with systemic inflammation and was associated with higher 28-day (45% versus 16%; P = 0.02) and 90-day (52% versus 19%; P = 0.01) mortality rates but not with transfusion requirements or bleeding. Prolonged time to initial fibrin formation (extrinsic TE assay >80 seconds) and Model for End Stage Liver Disease score at baseline were independent predictors of 28-day mortality. Conclusion: Patients with ACLF frequently show hypocoagulable features with prolonged time to initial fibrin formation and clot formation time and reduced clot firmness; these alterations worsen after admission, correlate with systemic inflammation, and translate into higher short-term mortality; hypofibrinolysis could contribute to organ failure in ACLF. PMID- 29790189 TI - The identification of a novel antibody for CD133 using human antibody phage display. AB - BACKGROUND: The transmembrane glycoprotein CD133 is believed to be a marker of adult prostate stem cells and cancer stem/initiating cells. Investigating the role of CD133 in the normal biology of the prostate and in cancer is complicated by the lack of a sensitive and accurate antibody for its detection. Here, we describe the characterization of a unique antibody identified using human antibody phage display that can recognize CD133 in both formalin-fixed tissues and cell lines. METHODS: A human single-chain variable fragment (scFv) antibody phage display library possessing a diversity of 8 * 109 was screened against fully glycosylated recombinant CD133. A counter screen was performed against deglycosylated CD133 to select for clones that preferentially recognized a glycosylation-independent epitope. The lead scFv was analyzed by flow cytometry and cloned into a rabbit immunoglobulin scaffold for immunohistochemistry (IHC). RESULTS: The antibody designated HA10 was found to bind a glycosylation independent epitope on the peptide backbone of CD133 with high affinity. As a reagent for flow cytometry, HA10 detected CD133 more accurately than a commonly used commercially available antibody. IHC analysis with HA10 documented the staining of basal cells and luminal cells in healthy prostate sections. Weak staining of luminal cells was observed in adenocarcinoma sections at a very low frequency. Examination of a LuCaP patient-derived xenograft tissue microarray found that only three of the LuCaP models were positive for CD133. The three CD133pos LuCaP models all originated from non-AR driven metastatic prostate cancer with neuroendocrine differentiation. Subsequent interrogation of liver biopsies from a patient who failed second-generation anti-androgen therapy found high levels of CD133 staining. The original transurethral resection of the prostate from that patient was, however, absent of CD133. CONCLUSIONS: We have developed a novel antibody that was able to detect CD133 by both IHC and flow cytometry. Using HA10 as an IHC reagent, we found that CD133 is a marker for a very rare cell type in both healthy prostate and adenocarcinoma sections. Our preliminary investigation also suggests that there may be an association between CD133 and non-AR driven prostate cancer with neuroendocrine differentiation. PMID- 29790191 TI - Pay It Forward: Building Capacity to Treat Hepatitis C by Training Our Own Residents. PMID- 29790190 TI - SimPEL: Simulation-based power estimation for sequencing studies of low prevalence conditions. AB - Power estimations are important for optimizing genotype-phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill-suited for the inherent challenges of studies for low-prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation-based program providing power estimations for the design of low-prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low-frequency condition studies. SimPEL, as a tool, provides researchers studying low-frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform-independent "batteries included" executable and default input files are available at https://github.com/precisionomics/SimPEL. PMID- 29790192 TI - Spontaneous scar-based reentrant atrial flutter: Electrophysiologic characteristics and ablation outcome in a retrospective analysis. AB - BACKGROUND: The understanding of spontaneous scar-based reentrant atrial arrhythmia is limited. We aim to characterize the electrophysiologic and mapping features of spontaneous scar-based atrial flutter (AFL) and outcomes of catheter ablation. METHODS: Consecutive patients with a diagnosis of AFL who underwent catheter ablation from January 2012 to June 2015 were screened. Scars were detected in 12 patients and were included in this study. All had negative coronary angiography. These patients were divided into right AFL (seven patients) and left AFL groups (five patients) based on electrophysiologic mappings. RESULTS: Compared to patients with right AFL, the size of right atrium (RA) was smaller and left atrium (LA) was larger in the left AFL group. The proportion of the scar area was 11.1 +/- 11.7 % in the RA AFL group and 7.8 +/- 2.8 % in the LA AFL group. The difference was significant (P = 0.001). The acute success rates of ablation were 85.7% and 100%, respectively, in patients with right and left AFL (P = 0.304). During the follow-up, expansion of the scar area was noted in three patients with recurrent right AFL. No scar expansion was noted in one patient with recurrent left AFL. In addition, three patients with right AFL required permanent pacemaker implantation for sinus node dysfunction, and no one required pacemaker in patients with left AFL. CONCLUSIONS: Spontaneous scar could serve as substrate for AFL in RA or LA. Compared to left AFL, there was a higher rate of recurrence and pacemaker implantation in patients with right AFL. PMID- 29790193 TI - Myasthenic ophthalmoparesis: Time To resolution after initiating immune therapies. AB - INTRODUCTION: Although immunotherapies such as prednisone are effective in treating myasthenic muscle weakness, their effect on resolution of myasthenic induced persistent ophthalmoparesis is unknown. METHODS: We observed patients with myasthenia gravis during their first year of immunotherapy, documenting ophthalmoplegia scores and drug doses. RESULTS: Seventy-six of 87 cases had persistent ophthalmoparesis. With immunotherapy, the median time to resolution of ophthalmoparesis was 7 months, and 37% of cases resolved within 3 months. Patients starting therapy within 12 months of symptom onset were twice as likely to have resolution in the first year (P = 0.028). Resolution of ophthalmoparesis within 3 months, compared with later resolution, was associated with higher initial prednisone doses (mean 0.5 vs. 0.3 mg/kg/day; P = 0.014). However, 25% of the higher dose group also received intravenous immunoglobulin/plasma exchange; after their exclusion, the finding was not significant. DISCUSSION: One-third of cases with myasthenic ophthalmoparesis resolved within 3 months of immunotherapy, particularly in response to more aggressive immunotherapy. Muscle Nerve 58: 542 549, 2018. PMID- 29790194 TI - The impact of epidural analgesia on the duration of the second stage of labor. AB - BACKGROUND: We aimed to describe the length of second stage of labor in a contemporary cohort. We calculated the 5th, 50th, and 95th percentiles for second stage length stratified by parity and epidural analgesia use and evaluated the effect of labor induction and oxytocin augmentation in our cohort. METHODS: We did a retrospective analysis of all live, singleton, term vaginal deliveries in one tertiary hospital. Multivariate linear regression was used to evaluate second stage duration confounders. First, we calculated the second-stage length and presented it as 5th, 50th, and 95th percentiles stratified by epidural analgesia and parity. Second, we evaluated the effect of labor induction and oxytocin augmentation on second-stage length, and third, we determined the demographic and obstetrical confounders that affected second-stage length. RESULTS: Overall, 15 500 deliveries were included. Nulliparity, oxytocin augmentation, epidural use, birthweight, labor induction, lower body mass index, and higher maternal age were found to be significantly associated with prolongation of the second stage. Epidural use was associated with an additional 82 minutes for the 95th percentile for both nulliparas and multiparas and tripled the rate of prolonged second stage for the entire cohort. Labor induction was associated with clinically significant prolongation of the second stage in nulliparas with epidural analgesia only. Oxytocin was associated with longer duration of the second stage for nulliparas, regardless of epidural use. DISCUSSION: Our findings suggest a significant prolongation of the second stage in women receiving epidural analgesia. Recommendations for management of second stage should be reconsidered by contemporary data. PMID- 29790195 TI - A licence to drive? Neurological illness, loss and disruption. AB - The sense of freedom and independence that being able to drive generates may be taken for granted by many until it is threatened by illness. Drawing on the 'mobility turn' in social sciences that emphasises the social and emotional significance of the car (Sheller and Urry , ), this article presents secondary analysis of narratives of driving and its significance across four neurological conditions (epilepsy, Parkinson's disease, transient ischaemic attack and motor neurone disease). Taking an interactionist approach we explore how the withdrawal of a driving licence can represent not just a practical and emotional loss of independence, but also loss of enjoyment; of a sense and feeling of 'normal' adulthood and social participation; and of an identity (in some cases gendered) of strength and power. Conversely the ability to keep driving can maintain an unbroken thread of narrative, for example enabling people with speech difficulties to feel and look normal behind the wheel. Moments of pleasure and normality illuminate the importance of examining the micro-strands of disruption illness can cause. PMID- 29790196 TI - Rituximab Is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A Phase 2 Randomized Controlled Trial. AB - : Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue, which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the antimitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B-cell depletion therapy will improve fatigue. In our single-center phase 2 randomized controlled trial, 57 participants aged 18 years or older with PBC and moderate to severe fatigue were randomized to receive two doses of either rituximab (1000 mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC-40 fatigue domain at 3 months. Secondary outcome measures included patient reported outcomes and immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference -0.9 [95% confidence interval 4.6 to 3.1]). Little difference was observed in other patient-reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the rituximab group, only but this was not associated with fatigue improvement. No treatment-emergent serious adverse events were seen. CONCLUSIONS: Rituximab was safe over the 12-month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen, potentially linking AMA with muscle bioenergetics dysfunction; however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely ursodeoxycholic acid (UDCA)-responding, early-disease stage cohort. (Hepatology 2018; 00:000 000). PMID- 29790197 TI - Establishing a publicly available national database of US news articles reporting agriculture-related injuries and fatalities. AB - BACKGROUND: The AgInjuryNews system and dataset are a news report repository and information source for agricultural safety professionals, policymakers, journalists, and law enforcement officials. METHODS: AgInjuryNews was designed as a primary storage and retrieval system that allows users to: identify agricultural injury/fatality events; identify injury agents and emerging issues; provide safety messages for media in anticipation of trends; and raise awareness and knowledge of agricultural injuries and prevention strategies. Data are primarily collected through Google Alerts and a digital media subscription service. Articles are screened, reviewed, coded, and entered into the system. RESULTS: As of January 1, 2018, the system contained 3028 unique incidents. Of those, 650 involved youth, and 1807 were fatalities. The system also had registered 329 users from 39 countries. CONCLUSIONS: AgInjuryNews combines injury reports into one dataset and may be the most current and comprehensive publicly available collection of news reports on agricultural injuries and deaths. PMID- 29790198 TI - The role of lysosomes and autophagosomes in frontotemporal lobar degeneration. AB - INTRODUCTION: Cell biological and genetic evidence implicate failures in degrading aggregating proteins, such as tau and TDP-43, through the autophagy or lysosomal pathways in the pathogenesis of frontotemporal lobar degeneration (FTLD). METHODS: We investigated changes in the degradative pathways in 60 patients with different pathological or genetic forms of FTLD employing immunohistochemistry for marker proteins such as lysosomal-associated membrane proteins 1 (LAMP-1) and 2 (LAMP-2), cathepsin D (CTSD) and microtubule-associated protein 1 light chain 3 alpha (LC3A). Immunostained sections were qualitatively and semi-quantitatively assessed for the appearance, distribution and intensity of staining in neurones of the dentate gyrus (DG) and CA4 region of the hippocampus, and the temporal cortex (Tcx). RESULTS: Lower levels of neuronal LAMP-1 immunostaining were present in the DG and Tcx in FTLD-tau compared to FTLD TDP. There was less LAMP-1 immunostaining in FTLD-tau with MAPT mutations, and FTLD-tau with Pick bodies, compared to FTLD-TDP types A and B, and less LAMP-1 immunostaining in FTLD-TDP type C than in FTLD-TDP types A and B. There was greater LAMP-1 immunostaining in GRN mutation which may reflect the underlying type A histology rather than mutation. There were no differences in neuronal LAMP 2, CTSD, EEA-1 or LC3A immunostaining between any of the five FTLD histological or four genetic groups, nor between FTLD-TDP and FTLD-tau. CONCLUSIONS: The underlying pathological mechanism in FTLD-tau may lie with a relative deficiency of lysosomes, or defective vesicular transport, whereas the failure to clear TDP 43 aggregates may lie with lysosomal dysfunction rather than a lack of available lysosomes or degradative enzymes. PMID- 29790200 TI - Sleep duration and mortality - Does weekend sleep matter? AB - Previous studies have found a U-shaped relationship between mortality and (weekday) sleep duration. We here address the association of both weekday and weekend sleep duration with overall mortality. A cohort of 43,880 subjects was followed for 13 years through record-linkages. Cox proportional hazards regression models with attained age as time-scale were fitted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals for mortality; stratified analyses on age (<65 years, >=65 years) were conducted. Among individuals <65 years old, short sleep (<=5 hr) during weekends at baseline was associated with a 52% higher mortality rate (hazard ratios 1.52; 95% confidence intervals 1.15-2.02) compared with the reference group (7 hr), while no association was observed for long (>=9 hr) weekend sleep. When, instead, different combinations of weekday and weekend sleep durations were analysed, we observed a detrimental association with consistently sleeping <=5 hr (hazard ratios 1.65; 95% confidence intervals 1.22-2.23) or >=8 hr (hazard ratios 1.25; 95% confidence intervals 1.05-1.50), compared with consistently sleeping 6-7 hr per day (reference). The mortality rate among participants with short sleep during weekdays, but long sleep during weekends, did not differ from the rate of the reference group. Among individuals >=65 years old, no association between weekend sleep or weekday/weekend sleep durations and mortality was observed. In conclusion, short, but not long, weekend sleep was associated with an increased mortality in subjects <65 years. In the same age group, short sleep (or long sleep) on both weekdays and weekend showed increased mortality. Possibly, long weekend sleep may compensate for short weekday sleep. PMID- 29790199 TI - Relationship between cumulative ultraviolet exposure and cognitive function in a rural elderly Chinese population. AB - OBJECTIVES: Some researchers have focused on the relationship between vitamin D and cognition, but the conclusions are inconsistent. We estimated cumulative UV exposure could be used to represent the individual's long-term vitamin D status and investigated its association with global cognitive function in elderly Chinese. METHODS: A total of 641 participants aged 60 years and over were recruited in a rural area of Shenyang, China. All were interviewed to obtain data regarding sociodemographic characteristics and time spent outdoors. Cognitive function was evaluated using the Montreal Cognitive Assessment-Beijing version (MoCA-BJ). Images of skin from UV-exposed (dorsal hand) and UV-protected (inner forearm) sites from each individual were graded by the Beagley-Gibson system. Differences in skin-grade between the 2 sites were used to indicate cumulative UV exposure level. Subjects were grouped in tertiles based on skin-grade differences (<1.75, 1.75-2.74, and >= 2.75), representing low, medium, and high UV exposure levels, respectively. The MoCA-BJ score was classified in tertiles as low (<19), middle (19-22), and high (>=23) levels of cognition. Associations between cognitive function and UV exposure were analyzed using ordinal regression. RESULTS: Skin-grade differences were associated with self-reported time spent outdoors. After adjustment for age, gender, education, BMI, whether living alone, income, diet, hypertension, and diabetes, a high UV exposure level was associated with better cognitive function (odds ratio = 0.643, 95% confidence interval = 0.427-0.969). CONCLUSIONS: Greater cumulative UV exposure appears to be associated with better cognitive function in elderly adults. PMID- 29790201 TI - Self-employed individuals performing different types of work have different occupational safety and health problems. AB - INTRODUCTION: We assessed the occupational safety and health (OSH) issues of self employed individuals in Korea. METHODS: The working conditions and OSH issues in three groups were analyzed using the Korean Working Conditions Survey of 2014. RESULTS: Among self-employed individuals, "Physical work" was more common among males, whereas "Emotional work" was more common among females. Self-employed individuals performing "Mental work" had more education, higher incomes, and the lowest exposure to physical/chemical and ergonomic hazards in the workplace. In contrast, those performing "Physical work" were older, had less education, lower incomes, greater exposure to physical/chemical and ergonomic hazards in the workplace, and more health problems. Individuals performing "Physical work" were most vulnerable to OSH problems. CONCLUSION: The self-employed are a heterogeneous group of individuals. We suggest development of specific strategies that focus on workers performing "Physical work" to improve the health and safety of self-employed workers in Korea. PMID- 29790202 TI - Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK. AB - AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service L396 million annually, of which L243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources. PMID- 29790203 TI - Land-use trade-offs between tree biodiversity and crop production in the Atlantic Forest. AB - Trade-offs in ecosystem services (ES) have received increasing attention because provisioning services often come at the expense of biodiversity loss. When land use patterns are not maximally efficient relative to productivity, provisioning services, such as crop production, can often be increased without losing biodiversity. The Atlantic Forest (AF) encompasses dense, mixed, and seasonal forests and has high levels of endemism and anthropogenic threat. We examined trade-offs between biodiversity and crop production in the AF to provide insights into land-use management decisions. We developed a biodiversity metric that combines information on tree species richness, evolutionary distinctiveness, and rarity at the local level. We examined the extent to which the nature of ES trade offs differ among the 3 forest types. We assessed how annual deforestation rates and land management practices affect biodiversity and agricultural revenues. Finally, we tested whether it is possible to achieve the same total regional revenue without reducing biodiversity by improving local management practices. The 3 forest types had similar patterns in ES trade-offs, although within mixed forest patterns differed. Biodiversity appeared to be more sensitive to land-use change than crop revenues. Certain crops yielded up to 10 times higher values in some sites. Enhanced crop productivity may increase revenues without reducing biodiversity. Our results showed that to enhance human well-being without further conversion of AF, maximizing crop productivity is needed . Increasing efficiency of management outcomes by maintaining higher biodiversity and increasing provisioning services depends on knowledge of forest type, the comparative advantage of planting crops in the best places, and preserving species in a balanced manner across forests. PMID- 29790204 TI - Mechanistic Insights into Selective Oxidation of Polyaromatic Compounds using RICO Chemistry. AB - Ruthenium-ion-catalyzed oxidation (RICO) of polyaromatic hydrocarbons (PAHs) has been studied in detail using experimental and computational approaches to explore the reaction mechanism. DFT calculations show that regioselectivity in these reactions can be understood in terms of the preservation of aromaticity in the initial formation of a [3+2] metallocycle intermediate at the most-isolated double bond. We identify two competing pathways: C-C bond cleavage leading to a dialdehyde and C-H activation followed by H migration to the RuOx complex to give diketones. Experimentally, the oxidation of pyrene and phenanthrene has been carried out in monophasic and biphasic solvent systems. Our results show that diketones are the major product for both phenanthrene and pyrene substrates. These diketone products are shown to be stable under our reaction conditions so that higher oxidation products (acids and their derivatives) are assigned to the competing pathway through the dialdehyde. Experiments using 18 O-labelled water do show incorporation of oxygen from the solvents into products, but this may take place during the formation of the reactive RuO4 species rather than directly during PAH oxidation. When the oxidation of pyrene is carried out using D2 O, a kinetic isotope effect (KIE) is observed implying that water is involved in the rate-determining step leading to the diketone products. PMID- 29790205 TI - Hyperkalaemia in diabetes: a silent risk predicting poor outcomes. PMID- 29790206 TI - Efficacy and safety of transcatheter valve-in-valve replacement for Mitroflow bioprosthetic valve dysfunction. AB - OBJECTIVES: Bioprostheses with pericardial leaflets mounted externally on the stent pose a high risk for valve-in-valve (ViV) procedures. This study analyzed the efficacy and safety of ViV procedures for treating structural valve deterioration (SVD) in Mitroflow bioprostheses. METHODS: Between January 2012 and August 2017, 11 patients (mean age 80.3 +/- 5.6 years) were treated for SVD of Mitroflow bioprostheses with transcatheter ViV procedures (six transapical [TA] and five transfemoral [TF]) using balloon expandable bioprostheses. RESULTS: All patients but one were in NYHA class III-IV. Mean STS PROM, euroSCORE I, and euroSCORE II were 8 +/- 6.5%, 27.8 +/- 11.5%, and 12 +/- 5.9%, respectively. Two patients had a "porcelain aorta." The size of implanted valves were 23 mm in 10 cases and 26 mm in one case. One patient suffered a coronary occlusion during a TF approach. The mean volume of contrast used in TF implants was 163 +/- 69.8 mL. No contrast media were used in TA procedures. There was one in-hospital death (10%). At 1 year of follow-up, peak and mean aortic gradients were 25.5 +/- 5.8 mmHg and 15.5 +/- 5.7 mmHg, respectively. One patient had mild paravalvular regurgitation. Cumulative survival was 90.9% at 1 year, 70.7% at 2 years, and 53% at 3 years. CONCLUSIONS: ViV procedures with balloon-expandable aortic valves provide good hemodynamic and clinical mid-term results for treating patients with a degenerated Mitroflow aortic bioprosthesis. Special care must be taken in small aortic roots, when the stented valve is in the supra-annular position to avoid coronary ostial obstruction. PMID- 29790207 TI - The repeated bout effect can occur without mechanical and neuromuscular changes after a bout of eccentric exercise. AB - Changes in muscle fascicle mechanics have been postulated to underpin the repeated bout effect (RBE) observed following exercise-induced muscle damage (EIMD). However, in the medial gastrocnemius (MG), mixed evidence exists on whether fascicle stretch amplitude influences the level of EIMD, thus questioning whether changes in fascicle mechanics underpin the RBE. An alternative hypothesis is that neural adaptations contribute to the RBE in this muscle. The aim of this study was to investigate the neuromechanical adaptations during and after repeated bouts of a highly controlled muscle lengthening exercise that aimed to maximize EIMD in MG. In all, 20 subjects performed two bouts of 500 active lengthening contractions (70% of maximal activation) of the triceps surae, separated by 7 days. Ultrasound constructed fascicle length-torque (L-T) curves of MG, surface electromyography (EMG), maximum torque production, and muscle soreness were assessed before, 2 hours and 2 days after each exercise bout. The drop in maximum torque (4%) and the increase in muscle soreness (24%) following the repeated bout were significantly less than following the initial bout (8% and 59%, respectively), indicating a RBE. However, neither shift in the L-T curve nor changes in EMG parameters were present. Furthermore, muscle properties during the exercise were not related to the EIMD or RBE. Our results show that there are no global changes in gastrocnemius mechanical behavior or neural activation that could explain the observed RBE in this muscle. We suggest that adaptations in the non-contractile elements of the muscle are likely to explain the RBE in the triceps surae. PMID- 29790208 TI - Changes in nano-mechanical properties of human epidermal cornified cells depending on their proximity to the skin surface. AB - During formation of the stratum corneum (SC) barrier, terminally differentiated keratinocytes continue their maturation process within the dead superficial epidermal layer. Morphological studies of isolated human corneocytes have revealed differences between cornified envelopes purified from the deep and superficial SC. We used atomic force microscopy to measure the mechanical properties of native human corneocytes harvested by tape-stripping from different SC depths. Various conditions of data acquisition have been tested and optimized, in order to obtain exploitable and reproducible results. Probing at 200 nN allowed us to investigate the total stiffness of the cells (at 50 nm indentation) and that of the cornified envelopes (at 10 to15 nm), and lipid envelopes (at 5 to 10 nm). The obtained data indicated statistically significant differences between the superficial (more rigid) and deep (softer) corneocytes, thus confirming the existence of depth and maturation-related morphological changes within the SC. The proposed approach can be potentially used for minimally invasive evaluation of various skin conditions such as aging, skin hydration, and pathologies linked to SC. PMID- 29790209 TI - Subclinical leaflet thrombosis following transcatheter aortic valve replacement. AB - Since the inception of transcatheter aortic valve replacement (TAVR), there have been significant reductions in complications due to improvements of transcatheter heart valve (THV) designs and technologies. Given expanding TAVR applications, reducing complications further and better understanding THV durability has become a focus within the structural heart space. Recently, dedicated cardiac computed tomographic angiography (CTA) performed at 1 month post-TAVR has identified subclinical leaflet thrombosis (SLT), with rates as high as 40%. From the SLT imaging hallmarks of hypoattenuated leaflet thickening (HALT) to hypoattenuation affecting motion (HAM), a postulated timeline of THV thrombosis advancing to clinical symptoms can be recognized. This review article focuses on leaflet thrombosis particularly following TAVR explaining the spectrum of this disease process, its diagnosis, current treatment options, and future directions in the field. PMID- 29790210 TI - A Highly Stable Two-Dimensional Copper(II) Organic Framework for Proton Conduction and Ammonia Impedance Sensing. AB - This work reports the design and fabrication of a proton conductive 2D metal organic framework (MOF), [Cu(p-IPhHIDC)]n (1) (p-IPhH3 IDC=2-(p-N-imidazol-1-yl) phenyl-1 H-imidazole-4,5-dicarboxylic acid) as an advanced ammonia impedance sensor at room temperature and 68-98 % relative humidity (RH). MOF 1 shows the optimized proton conductivity value of 1.51*10-3 S cm-1 at 100 degrees C and 98 % RH. Its temperature-dependent and humidity-dependent proton conduction properties have been explored. The large amount of uncoordinated carboxylate groups between the layers plays a vital role in the resultant conductivity. Distinctly, the fabricated MOF-based sensor displays the required stability toward NH3 , enhanced sensitivity, and notable selectivity for NH3 gas. At room temperature and 68 % RH, it gives a remarkable gas response of 8620 % to 130 ppm NH3 gas and lower detection limit of 2 ppm towards NH3 gas. It is also found that the gas response of the ammonia sensor increases linearly with the increase of NH3 gas concentration under 68-98 % RH and room temperature. Moreover, the sensor indicates excellent reversibility and selectivity toward NH3 versus N2 , H2 , O2 , CO, CO2 , benzene, and MeOH. Based on structural analyses, activation energy calculations, water and NH3 vapor absorptions, and PXRD determinations, proton conduction and NH3 sensing mechanisms are suggested. PMID- 29790211 TI - Opening the black box: An observational study of teaching and learning interactions for paediatrics trainees on consultant ward rounds. AB - AIM: Ward rounds are complex activities in which education must be balanced against service. Limited evidence exists regarding how to optimise ward round education. In order to improve the educational experience, we aimed to understand the teaching and learning interactions on ward rounds with a particular focus on the experience of paediatric trainees. METHODS: We conducted an initial quantitative survey as a needs assessment regarding learning and teaching in clinical settings using a structured survey of 21 trainees. This was followed by an observational study using focused ethnography of 20 consultant ward rounds in a general medical department of tertiary paediatric hospital. We used a structured observation form to document ward round characteristics and educational interactions. Data were analysed using inductive content analysis to understand key influences on teaching and learning interactions. RESULTS: Trainees reported a discrepancy between the actual educational value of ward rounds (mean rating 2.7/5) and what they desired (mean 4.3/5). Ward round ethnography revealed examples of excellent education and practice alongside missed opportunities. Explicit education on rounds was dominated by technical content with little focus on other aspects of professionalism. Major influences on educational interactions were the ward round model - consultant-as-expert versus learner-centred - and the hidden curriculum. CONCLUSION: There are many examples of excellence in ward round education, yet there remains substantial scope to better harness the education potential of rounds. This requires us to challenge assumptions, enable feedback and reflection and make learning explicit while putting the learner at the centre of educational opportunities. PMID- 29790212 TI - Dopamine in transplantation: Written off or comeback with novel indication? AB - Renal-dose dopamine has fallen out of favor in the intensive care unit (ICU) during past years due to its ineffectiveness to prevent impending or to ameliorate overt renal failure in the critically ill. By contrast, growing evidence indicates that low-dose dopamine administered to the stable organ donor after brain death confirmation improves the clinical course of transplanted organs after kidney and heart transplantation. Ensuring a thorough monitoring for potential circulatory side effects, employment of dopamine at a dose of 4 MUg/kg/min is safe in the deceased donor. Among recipients, the advantageous effect is easy to achieve, inexpensive, and devoid of adverse side effects. The mode of action relies on dopamine's propensity to mitigate injury in various cell systems from isolated transplantable organs under cold storage conditions. The present review article summarizes the clinical evidence of dopamine donor pretreatment in solid organ transplantation and focuses on the underlying molecular mechanisms of cellular protection. Introducing the routine use of low dose dopamine for the management of the brain-dead donor in the ICU before procurement provides an evidence-based strategy to improve graft outcome after kidney transplantation without conferring harm to non-renal grafts, namely to livers and hearts, in cases of multi-organ donation. PMID- 29790213 TI - Integration of Biomaterials into Sensors Based on Organic Thin-Film Transistors. AB - Sensors based on organic thin-film transistors (OTFTs) present various advantages, including high sensitivity and mechanical flexibility, thus possessing potential applications such as wearable devices and biomedical electronics for health monitoring, etc. However, such applications are partially limited by the biocompatibility, biodegradability, and sensitivity to target analytes of OTFT-based sensors, which can be improved by the incorporation of diverse biomaterials. This article presents a brief review from the viewpoint of the type of the integrated biomaterials, including naturally occurring biomacromolecules such as proteins, enzymes, and deoxyribonucleic acid, as well as biocompatible polymers such as polylactide, poly(lactide-co-glycolide), poly(ethylene glycol), cellulose, polydimethylsiloxane, parylene, etc. It is believed that future work in this field should be devoted to the selectivity, sensitivity, and stability improvement as well as the high-level integration and sophistication on the basis of the OTFT-based sensors for physical, chemical, and biological sensing applications. PMID- 29790214 TI - Predictability of demographic rates based on phylogeny and biological similarity. AB - Lack of demographic data for most of the world's threatened species is a widespread problem that precludes viability-based status assessments for species conservation. A commonly suggested solution is to use data from species that are closely related or biologically similar to the focal species. This approach assumes similar species and populations of the same species have similar demographic rates, an assumption that has yet to be thoroughly tested. We constructed a Bayesian hierarchical model with data on 425 plant species to predict demographic rates (intrinsic rate of population growth, recruit survival, juvenile survival, adult survival, and fecundity) based on biological traits and phylogenetic relatedness. Generally, we found small effects of species-level traits (except woody polycarpic species tended to have high adult survival rates that increased with plant height) and a weak phylogenetic signal for 4 of the 5 demographic parameters examined. Patterns were stronger in adult survival and fecundity than other demographic rates; however, the unexplained variances at both the species and population levels were high for all demographic rates. For species lacking demographic data, our model produced large, often inaccurate, prediction intervals that may not be useful in a management context. Our findings do not support the assumption that biologically similar or closely related species have similar demographic rates and provide further evidence that direct monitoring of focal species and populations is necessary for informing conservation status assessments. PMID- 29790216 TI - Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma. AB - BACKGROUND: Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC. METHODS: The expression levels of hsa_circ_0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real-time polymerase chain reaction. The relationships between the expression of hsa_circ_0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa_circ_0137287 as a biomarker for PTC. RESULTS: The expression of hsa_circ_0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa_circ_0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa_circ_0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452-0.9494, P < .0001), 0.6885 (95%CI = 0.5908-0.7862, P = .0009), and 0.6691(95%CI = 0.5641-0.7742, P = .0034), respectively. CONCLUSIONS: Our findings suggest that hsa_circ_0137287 may serve as a novel biomarker for PTC. PMID- 29790215 TI - Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement. AB - NEW FINDINGS: What is the central question of this study? Do systemic sclerosis patients exhibit impaired nitric oxide-mediated vascular function of the lower limb and are these decrements correlated with plasma biomarkers for inflammation and oxidative stress? What is the main finding and its importance? Findings indicate impaired nitric oxide-mediated vascular function, linked to the incidence of digital ulcers and a milieu of inflammation and oxidative stress. However, the absence of significant correlations between individual biomarkers and blood flow responses suggests that the vasculopathy observed in systemic sclerosis may not be solely the result of derangements in the redox balance or inflammatory signalling. ABSTRACT: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, which may be the consequence of inflammation and oxidative stress that ultimately leads to a reduced nitric oxide (NO) bioavailability. Passive leg movement (PLM) is a novel methodology for assessing lower limb vascular function that is predominantly NO dependent. We combined this vascular assessment with a comprehensive panel of plasma biomarkers to assess the axis of inflammation, oxidative stress and NO in SSc patients (n = 12; 62 +/- 11 years of age) compared with healthy control subjects (n = 17; 60 +/ 16 years of age). The PLM-induced changes in leg blood flow (LBF; 191 +/- 104 versus 327 +/- 217 ml min-1 ) and LBF area under the curve (39 +/- 104 versus 125 +/- 131 ml) were reduced in SSc compared with control subjects. Stratification of patients according to history of digital ulcer (DU) formation revealed a further reduction in LBF area under the curve in DU (-13 +/- 83 ml) versus non-DU (91 +/- 102 ml) patients. Biomarkers of inflammation (C-reactive protein) and oxidative stress (malondialdehyde and protein carbonyl) were all elevated in SSc (C reactive protein, 3299 +/- 2372 versus 984 +/- 565 ng ml-1 ; malondialdehyde, 3.2 +/- 1.1 versus 1.1 +/- 0.7 MUm; and protein carbonyl, 0.15 +/- 0.05 versus 0.12 +/- 0.03 nmol mg-1 ), and C-reactive protein was further elevated in patients with a history of DU (4551 +/- 2752 versus 2047 +/- 1019 ng ml-1 ) compared with non-DU, although these were not individually correlated with changes in LBF. These findings of impaired NO-mediated vascular function, linked to DU and a milieu of inflammation and oxidative stress, suggest that redox balance plays an important, but not necessarily deterministic, role in the vascular pathophysiology of SSc. PMID- 29790217 TI - A sonographic classification and reporting system for diagnosing adenomyosis. AB - OBJECTIVE: To develop a uniform classification and standardized reporting system of ultrasound findings of adenomyosis using the Morphological Uterus Sonographic Assessment (MUSA) criteria. METHOD: The opinion presented in this manuscript was built based on a thorough discussion among all authors, including a Delphi procedure. Selected images and videos of typical cases of the different morphological variations of adenomyosis were used in the debates. RESULTS: A classification and reporting system of different types of adenomyosis based on ultrasound was agreed upon including (1) identification of adenomyosis based on MUSA criteria, (2) disease location (anterior, posterior, left lateral, right lateral, fundal), (3) classification of the lesions as focal or diffuse, (4) presence or absence of intralesional cysts, (5) myometrial layer involvement (junctional zone, myometrium, serosal involvement), (6) disease extent (< 25%, 25 50%, > 50% of uterine volume affected by adenomyosis) and (7) lesion size. CONCLUSIONS: We proposes a uniform classification and reporting system of different types of adenomyosis based on ultrasound. The clinical relevance of this approach needs to be evaluated in further studies. This article is protected by copyright. All rights reserved. PMID- 29790218 TI - Lost in transition: finding a path forward for young adults with Type 1 diabetes. PMID- 29790219 TI - Metal-Organic Frameworks Based on Multicenter-Bonded [MI ]8 (M=Mn, Zn) Clusters with Cubic Aromaticity. AB - A new concept for constructing metal-organic frameworks (MOFs) based on multicenter-bonded [MI ]8 (M=Mn, Zn) clusters with cubic aromaticity is discussed. In principle, intermolecular/intramolecular hydrogen-bonding, pi-pi stacking, coordinated covalent bonding and ionic bonding usually account for the structures of MOFs, and multicentered bonds generally exist in cation, anion, neutral and zwitterionic radicals, while rarely appear in MOFs. Meanwhile, aromaticity became one of the most vexing yet fascinating key concepts in chemistry since the proposition of the structure of benzene molecule in 1865. In this context, this concept article exhibits the preparation, structures, characterization methods, theoretical analysis of current research for MOFs which feature with multicentered bonding [MI ]8 (M=Mn, Zn) cluster with cubic aromaticity, followed by their fluorescence probe and magnetic properties are also summarized. Finally, prospective outlook in this field is given. PMID- 29790220 TI - A Novel Linking Strategy of Using 9,10-Dihydroacridine to Construct Efficient Host Materials for Red Phosphorescent Organic Light-Emitting Diodes. AB - Three novel 9,10-dihydroacridine derivatives, 4'-(10-methyl-9,9-diphenyl-9,10 dihydroacridin-4-yl)[1,1'-biphenyl]-4-carbonitrile (MeAcPhCN), 4'-(9,9,10 triphenyl-9,10-dihydroacridin-4-yl)[1,1'-biphenyl]-4-carbonitrile (PhAcPhCN), and 5-[4-(9,9,10-triphenyl-9,10-dihydroacridin-4-yl)phenyl]picolinonitrile (MeAcPyCN), were prepared by the attachment of [1,1'-biphenyl]-4-carbonitrile or 5-phenylpicolinonitrile to the 4-position of 9,10-dihydroacridine. This special linking strategy limited the conjugation length, maintained the triplet energy, and inhibited the intermolecular charge-transfer (ICT) characteristics of these compounds. Notably, the enhanced accepting strength of the picolinonitrile segment relative to that of benzonitrile led to relatively strong ICT characteristics, a low energy gap, and a low triplet energy for MeAcPyCN. The thermal, photophysical, electrochemical, and electroluminescent properties of these host materials were studied systematically. Consequently, (acetylacetonato)bis(2-methyldibenzo[f,h]quinoxaline)iridium(III) [Ir(MDQ)2 (acac)]-based red phosphorescent organic light-emitting diodes (PHOLEDs) were fabricated with these three host materials. As a result, the device hosted by MeAcPhCN showed good device performance with a maximum external quantum efficiency of 20.5 %. PMID- 29790221 TI - Exploring the effect of a lifestyle intervention on cancer risk: 43-year follow up of the randomized Oslo diet and antismoking study. AB - BACKGROUND/OBJECTIVES: The Oslo diet and antismoking study showed that counselling for a healthy lifestyle reduced lifelong coronary mortality in high risk men. We explored whether the same counselling reduced also cancer risk. METHODS: The study randomly allocated males at high coronary risk to either a 5 year intervention for lifestyle changes (cholesterol-lowering dietary changes, weight loss and stopping smoking) or a control group (1 : 1) in 1972/73. We explored the incidence and mortality of all cancers and cancer forms related to smoking, BMI or diet up to 43 years after randomization. RESULTS: A total of 595 men in the intervention and 621 in the control group were included. At inclusion median age was 45 years, 588 (48.4%) subjects were overweight (BMI > 25 kg m-2 ) and 925 (76.1%) current smokers. The intervention did not reduce the risk of cancer after 43 years (adjusted hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.80-1.15). In the first 25 years of follow-up, among the 1088 (89.5%) men who were overweight/obese and/or smokers, the intervention reduced the incidence of those cancer forms related to smoking, BMI or diet (including carcinoma of the respiratory, digestive and urinary tracts; adjusted HR 0.69; 95% CI 0.49-0.99). The intervention had no significant effect on incidence beyond 25 years, or on mortality. CONCLUSIONS: The 5-year counselling for a healthy lifestyle did not reduce the overall cancer risk in the very long term. However, in the first 25 years, the counselling reduced the risk of relevant cancer types in overweight/obese subjects and smokers. PMID- 29790222 TI - Monitoring the Hydrothermal Growth of Cobalt Spinel Water Oxidation Catalysts: From Preparative History to Catalytic Activity. AB - The hydrothermal growth of cobalt oxide spinel (Co3 O4 ) nanocrystals from cobalt acetate precursors was monitored with in situ powder X-ray diffraction (PXRD) in combination with ex situ electron microscopy and vibrational spectroscopy. Kinetic data from in situ PXRD monitoring were analyzed using Sharp-Hancock and Gualtieri approaches, which both clearly indicate a change of the growth mechanism for reaction temperatures above 185 degrees C. This mechanistic transition goes hand in hand with morphology changes that notably influence the photocatalytic oxygen evolution activity. Complementary quenching investigations of conventional hydrothermal Co3 O4 growth demonstrate that these insights derived from in situ PXRD data provide valuable synthetic guidelines for water oxidation catalyst production. Furthermore, the ex situ analyses of hydrothermal quenching experiments were essential to assess the influence of amorphous cobalt containing phases arising from the acetate precursor on the catalytic activity. Thereby, the efficient combination of a single in situ technique with ex situ analyses paves the way to optimize parameter-sensitive hydrothermal production processes of key energy materials. PMID- 29790223 TI - CORRIGENDUM. PMID- 29790224 TI - Left atrial compression and right ventricular outflow tract diameter on echocardiography are independently associated with exercise capacity in patients with large hiatal hernia. AB - INTRODUCTION: Large hiatal hernia (HH) is often associated with left atrial (LA) compression, anteroposterior cardiac compression (manifesting as reduced right ventricular outflow tract (RVOT) diameter), and left ventricular (LV) compression (manifesting as systolic paradoxical outward motion (LV-PM) of the posterobasal LV segment). Exercise impairment, also common in this population, improves following HH surgery. We aimed to identify echocardiographic parameters independently associated with exercise impairment due to HH-mediated cardiogenic compression. METHODS: Patients with a large HH (>30% intra-thoracic stomach, n = 163) referred for cardiac evaluation were included. Echocardiographic parameters were retrospectively analyzed in relation to HH-related LA compression severity and the presence of LV-PM. Echocardiographic parameters independently associated with exercise capacity were identified by multivariable analysis. RESULTS: Mean baseline metabolic equivalents were reduced (70 +/- 28% predicted). Moderate severe LA compression and LV-PM were present in 91 of 163 (56%) and 65 of 162 (40%) patients, respectively. Patients with moderate-severe LA compression and LV PM had decreased LA and LV dimensions. Moderate-severe LA compression was also associated with reduced RVOT diameter while LV-PM predicted a greater reduction in LV volumes. LA compression and RVOT diameter were independently associated with baseline exercise capacity and increased following HH surgery performed in a subgroup (n = 72, LA diameter: 14 +/- 5 vs 20 +/- 4 mm/m2 ; RVOT diameter: 17 +/- 3 vs 19 +/- 3 mm/m2 , P < .001 for both). Conversely, LV-PM was not independently associated with exercise capacity. CONCLUSION: Hiatal hernia-related cardiac compression reduces LA and RVOT dimensions. These parameters are independently associated with baseline exercise capacity and improve following HH surgery. LV PM is associated with decreased LV volumes but not exercise capacity in this population. PMID- 29790225 TI - Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography? AB - In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft-tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5-year all-cause mortality and 5-year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal-Wallis test, Kaplan-Meier curves, and the log-rank test. Over a mean duration of follow-up of 10.4 +/- 2.9 years (range: 0.01-12 years) post-CMR, the overall all-cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR-confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy. PMID- 29790227 TI - Experimental Realisation of Elusive Multiple-Bonded Aluminium Compounds: A New Horizon in Aluminium Chemistry. AB - The synthesis and isolation of stable main group compounds featuring multiple bonds has been of great interest for several decades. A plethora of such multiply bonded complexes have been obtained by using sterically demanding substituents that provide both kinetic and thermodynamic stability. Most of these compounds have unusual structural and electronic properties that challenge the classical concept of covalent multiple bonding. In contrast, analogous aluminium compounds are scarce in spite of its high natural abundance. The parent dialumene (Al2 H2 ) has been calculated to be extremely unstable, thus making compounds containing Al multiple bonds a challenging synthetic target. This Review provides an overview of the recent advances in the cutting edge synthetic approaches and the careful ligand design used to obtain aluminium homo- and heterodiatomic multiply bonded complexes. In addition, the reactivity of these novel compounds towards various small molecules and reagents will be discussed herein. PMID- 29790228 TI - Evidence-based dentistry skill acquisition by second-year dental students. AB - INTRODUCTION: Identification and assessment of Evidence-based dentistry (EBD) outcomes have been elusive. Our objective was to describe EBD skill acquisition during the second (D2) year of pre-doctoral dental education and student competency at the end of the year. METHODS: The first and fourth (final) curricular-required EBD Exercises (ie, application of the first 4 steps of the 5 Step evidence-based practice process applied to a real or hypothetical situation) completed by D2 students (n = 151) during 2014-2015 and 2015-2016 were evaluated to measure skill acquisition through use of a novel rubric with measures of performance from novice to expert. Exercises were evaluated on the performance for each step, identification of manuscript details and reflective commentary on manuscript components. Changes in performance were evaluated using the chi-square test for trend and the Wilcoxon signed-rank test. RESULTS: Seventy-eight per cent of students scored competent or higher on the Ask step at the beginning of the D2 year; scores improved with 58% scoring proficient or expert on the fourth Exercise (P < .001). Most students were advanced beginners or higher in the Acquire, Appraise and Apply steps at the beginning of the D2 year, with minimal growth observed during the year. Identification of manuscript details improved between the first and fourth Exercises (P = .015); however, depth of commentary skills did not change. DISCUSSION: Unlike previous investigations evaluating EBD knowledge or behaviour in a testing situation, we evaluated skill acquisition using applied Exercises. CONCLUSION: Consistent with their clinical and scientific maturity, D2 students minimally performed as advanced beginners at the end of their D2 year. PMID- 29790226 TI - Comparative analysis of AKT and the related biomarkers in uterine leiomyomas with MED12, HMGA2, and FH mutations. AB - Uterine leiomyomas (ULM) are histologically and molecularly heterogeneous and clinically they grow at vastly different rates. Several driver gene mutations have been identified in ULM, including MED12 mutations, HMGA2 overexpression, and biallelic FH inactivation. ULM with different driver mutant genes may use different molecular pathways, but currently no clear correlation between gene mutations and growth related pathways has been established. To better define this relationship, we collected ULM with MED12 (n = 25), HMGA2 (n = 15), and FH (n = 27) mutations and examined the sex steroid hormone, cell cycle, and AKT pathway genes by immunohistochemistry. While ER and PR were highly expressed in all types of ULM, FH ULM showed lower ER expression and higher PR expression. HMGA2 tumors had significantly higher levels of AKT signaling and mitogenic activity than other ULM types. HMGA2 activated AKT signaling through upregulation of IGF2BP2. Silencing HMGA2 in ULM cells resulted in downregulation of AKT and upregulation of p16 and p21, which eventually led to cell senescence. HMGA2 overexpression in ULM is not only related to tumor development but also plays a role in controlling cellular proliferation through the AKT pathway. PMID- 29790229 TI - Global Lung Initiative 2012 spirometry reference values in a large Asian cohort of Malay, Chinese and Indian ancestry. AB - BACKGROUND AND OBJECTIVE: Although the multi-ethnic European Respiratory Society/Global Lung Initiative (ERS/GLI) 2012 reference values have been developed, the Taskforce has called for further validation specifically on subpopulations that were under represented such as the Malays, Chinese and Indians, in which the two latter ethnic groups represent about one-third of the world population. Thus, the aims of this study were to evaluate the appropriateness of the ERS/GLI 2012 reference values in a healthy adult Malaysian population and to construct a local lung function reference for the Malaysia population specific to the three major ethnic groups. METHODS: Acceptable spirometry data were obtained from 30 281 healthy subjects aged 35-70 years comprising Malays, Chinese and Indians from the Malaysian Cohort. Local reference values were calculated using regression analysis and evaluated using ERS/GLI reference values to obtain GLI Z-scores. RESULTS: The mean (SD) of the forced expiratory volume in 1 s (FEV1 ) for males were 2.67 (0.46), 2.89 (0.48) and 2.60 (0.46) and females were 1.91 (0.36), 2.13 (0.37) and 1.86 (0.35) for Malays, Chinese and Indians, respectively. For forced vital capacity (FVC), the mean (SD) for males were 3.03 (0.53), 3.28 (0.58) and 2.92 (0.53) and females were 2.15 (0.40), 2.38 (0.43) and 2.07 (0.41) for Malays, Chinese and Indians, respectively. The mean GLI Z-scores were less than -0.5 for FEV1 and FVC and more than 0.5 for FEV1 /FVC. A large percentage of subjects in all the three ethnic groups were defined lower than the lower limit of normal. CONCLUSION: This present and large multi-ethnic Asian-based study demonstrates clinically significant deviation from ERS/GLI 2012 equations for spirometry. It highlights the importance of validating predicted equations for spirometry in local populations. PMID- 29790231 TI - A qualitative investigation of hospital visitors' experiences using the analytic lens of liminality: Informing nursing practice and policy. AB - This research aimed to inform nursing practice and policy by identifying satisfying and problematic experiences of hospital visitors during the hospitalisation episode of a significant other. An extensive contextual review revealed that healthcare systems in advanced economies face multiple pressures and that in England, the government leaves the determination of hospital visiting rules to individual trusts. The analytic lens of liminality provides rich interpretations of visitors' accounts and demonstrates the importance to visitors of structure (hospital rules and systems) and communitas (social bonding among liminal personae). Supportive hospital structures reduce the challenges of liminality and increase satisfaction. The data further suggest an extension to current understandings of liminality. Strong structure and successful communitas permit a safe exit from liminality after the hospitalisation episode for visitors with a close emotional bond with the patient. PMID- 29790230 TI - Visualizing the quantile survival time difference curve. AB - The difference between the pth quantiles of 2 survival functions can be used to compare patients' survival between 2 therapies. Setting p = 0.5 yields the median survival time difference. Varying p between 0 and 1 defines the quantile survival time difference curve which can be straightforwardly estimated by the horizontal differences between 2 Kaplan-Meier curves. The estimate's variability can be visualized by adding either a bundle of resampled bootstrap step functions or, alternatively, approximate bootstrap confidence bands. The user-friendly SAS software macro %kmdiff enables the straightforward application of this exploratory graphical approach. The macro is described, and its application is exemplified with breast cancer data. The advantages and limitations of the approach are discussed. PMID- 29790232 TI - Rapid Photoactuation of a DNA Nanostructure using an Internal Photocaged Trigger Strand. AB - A reconfigurable DNA nano-tweezer is reported that can be switched between a closed and open state with a brief pulse of UV light. In its initial state, the tweezer is held shut using a hairpin with a single-stranded poly-A loop. Also incorporated in the structure is a poly-T trigger strand bearing seven photocaged residues. Upon illumination with 365 nm light, the cages are removed and the trigger strand hybridizes to the loop, opening the tweezer and increasing the distance between its arms from 4 to 18 nm. This intramolecular process is roughly 60 times faster than adding an external trigger strand, and provides a mechanism for the rapid interconversion of DNA nanostructures with light. PMID- 29790233 TI - Factors regulating carbon sinks in mangrove ecosystems. AB - Mangroves are recognized as one of the richest carbon storage systems. However, the factors regulating carbon sinks in mangrove ecosystems are still unclear, particularly in the subtropical mangroves. The biomass, production, litterfall, detrital export and decomposition of the dominant mangrove vegetation in subtropical (Kandelia obovata) and tropical (Avicennia marina) Taiwan were quantified from October 2011 to July 2014 to construct the carbon budgets. Despite the different tree species, a principal component analysis revealed the site or environmental conditions had a greater influence than the tree species on the carbon processes. For both species, the net production (NP) rates ranged from 10.86 to 27.64 Mg C ha-1 year-1 and were higher than the global average rate due to the high tree density. While most of the litterfall remained on the ground, a high percentage (72%-91%) of the ground litter decomposed within 1 year and fluxed out of the mangroves. However, human activities might cause a carbon flux into the mangroves and a lower NP rate. The rates of the organic carbon export and soil heterotrophic respiration were greater than the global mean values and those at other locations. Only a small percentage (3%-12%) of the NP was stored in the sediment. The carbon burial rates were much lower than the global average rate due to their faster decomposition, indicating that decomposition played a critical role in determining the burial rate in the sediment. The summation of the organic and inorganic carbon fluxes and soil heterotrophic respiration well exceeded the amount of litter decomposition, indicating an additional source of organic carbon that was unaccounted for by decomposition in the sediment. Sediment-stable isotope analyses further suggest that the trapping of organic matter from upstream rivers or adjacent waters contributed more to the mangrove carbon sinks than the actual production of the mangrove trees. PMID- 29790234 TI - ClinVar Miner: Demonstrating utility of a Web-based tool for viewing and filtering ClinVar data. AB - ClinVar Miner is a Web-based suite that utilizes the data held in the National Center for Biotechnology Information's ClinVar archive. The goal is to render the data more accessible to processes pertaining to conflict resolution of variant interpretation as well as tracking details of data submission and data management for detailed variant curation. Here, we establish the use of these tools to address three separate use cases and to perform analyses across submissions. We demonstrate that the ClinVar Miner tools are an effective means to browse and consolidate data for variant submitters, curation groups, and general oversight. These tools are also relevant to the variant interpretation community in general. PMID- 29790236 TI - Forecasting zoonotic cutaneous leishmaniasis using meteorological factors in eastern Fars province, Iran: a SARIMA analysis. AB - OBJECTIVES: To predict the occurrence of zoonotic cutaneous leishmaniasis (ZCL) and evaluate the effect of climatic variables on disease incidence in the east of Fars province, Iran using the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. METHODS: The Box-Jenkins approach was applied to fit the SARIMA model for ZCL incidence from 2004 to 2015. Then the model was used to predict the number of ZCL cases for the year 2016. Finally, we assessed the relation of meteorological variables (rainfall, rainy days, temperature, hours of sunshine and relative humidity) with ZCL incidence. RESULTS: SARIMA(2,0,0) (2,1,0)12 was the preferred model for predicting ZCL incidence in the east of Fars province (validation Root Mean Square Error, RMSE = 0.27). It showed that ZCL incidence in a given month can be estimated by the number of cases occurring 1 and 2 months, as well as 12 and 24 months earlier. The predictive power of SARIMA models was improved by the inclusion of rainfall at a lag of 2 months (beta = -0.02), rainy days at a lag of 2 months (beta = -0.09) and relative humidity at a lag of 8 months (beta = 0.13) as external regressors (P-values < 0.05). The latter was the best climatic variable for predicting ZCL cases (validation RMSE = 0.26). CONCLUSIONS: Time series models can be useful tools to predict the trend of ZCL in Fars province, Iran; thus, they can be used in the planning of public health programmes. Introducing meteorological variables into the models may improve their precision. PMID- 29790235 TI - Self-Reporting Inhibitors: A Single Crystallization Process To Obtain Two Optically Pure Enantiomers. AB - Collection of two optically pure enantiomers in a single crystallization process can significantly increase the chiral separation efficiency but this is difficult to realize. Now a self-reporting strategy is presented for visualizing the crystallization process by a dyed self-assembled inhibitor made from the copolymers with tri(ethylene glycol)-grafting polymethylsiloxane as the main chain and poly(N6 -methacryloyl-l-lysine) as side chains. When applied with seeds together for the fractional crystallization of conglomerates, the inhibitors can label the formation of the secondary crystals and guide the complete separation process of two enantiomers with colorless crystals as the first product and red crystals as the second. This method leads to high optical purity of d/l-Asn?H2 O (99.9 % ee for d-crystals and 99.5 % for l-crystals) in a single crystallization process. It requires a small amount of additives and shows excellent recyclability. PMID- 29790237 TI - Towards a new classification of stable phase schizophrenia into major and simple neuro-cognitive psychosis: Results of unsupervised machine learning analysis. AB - RATIONALE: Deficit schizophrenia, as defined by the Schedule for Deficit Syndrome, may represent a distinct diagnostic class defined by neurocognitive impairments coupled with changes in IgA/IgM responses to tryptophan catabolites (TRYCATs). Adequate classifications should be based on supervised and unsupervised learning rather than on consensus criteria. METHODS: This study used machine learning as means to provide a more accurate classification of patients with stable phase schizophrenia. RESULTS: We found that using negative symptoms as discriminatory variables, schizophrenia patients may be divided into two distinct classes modelled by (A) impairments in IgA/IgM responses to noxious and generally more protective tryptophan catabolites, (B) impairments in episodic and semantic memory, paired associative learning and false memory creation, and (C) psychotic, excitation, hostility, mannerism, negative, and affective symptoms. The first cluster shows increased negative, psychotic, excitation, hostility, mannerism, depression and anxiety symptoms, and more neuroimmune and cognitive disorders and is therefore called "major neurocognitive psychosis" (MNP). The second cluster, called "simple neurocognitive psychosis" (SNP) is discriminated from normal controls by the same features although the impairments are less well developed than in MNP. The latter is additionally externally validated by lowered quality of life, body mass (reflecting a leptosome body type), and education (reflecting lower cognitive reserve). CONCLUSIONS: Previous distinctions including "type 1" (positive)/"type 2" (negative) and DSM-IV-TR (eg, paranoid) schizophrenia could not be validated using machine learning techniques. Previous names of the illness, including schizophrenia, are not very adequate because they do not describe the features of the illness, namely, interrelated neuroimmune, cognitive, and clinical features. Stable-phase schizophrenia consists of 2 relevant qualitatively distinct categories or nosological entities with SNP being a less well-developed phenotype, while MNP is the full blown phenotype or core illness. Major neurocognitive psychosis and SNP should be added to the DSM-5 and incorporated into the Research Domain Criteria project. PMID- 29790239 TI - Ocean warming has a greater effect than acidification on the early life history development and swimming performance of a large circumglobal pelagic fish. AB - Ocean warming and acidification are serious threats to marine life; however, their individual and combined effects on large pelagic and predatory fishes are poorly understood. We determined the effects of projected future temperature and carbon dioxide (CO2 ) levels on survival, growth, morphological development and swimming performance on the early life stages of a large circumglobal pelagic fish, the yellowtail kingfish Seriola lalandi. Eggs, larvae and juveniles were reared in cross-factored treatments of temperature (21 and 25 degrees C) and pCO2 (500 and 985 MUatm) from fertilisation to 25 days post hatching (dph). Temperature had the greatest effect on survival, growth and development. Survivorship was lower, but growth and morphological development were faster at 25 degrees C, with surviving fish larger and more developed at 1, 11 and 21 dph. Elevated pCO2 affected size at 1 dph, but not at 11 or 21 dph, and did not affect survival or morphological development. Elevated temperature and pCO2 had opposing effects on swimming performance at 21 dph. Critical swimming speed (Ucrit ) was increased by elevated temperature but reduced by elevated pCO2 . Additionally, elevated temperature increased the proportion of individuals that responded to a startle stimulus, reduced latency to respond and increased maximum escape speed, potentially due to the more advanced developmental stage of juveniles at 25 degrees C. By contrast, elevated pCO2 reduced the distance moved and average speed in response to a startle stimulus. Our results show that higher temperature is likely to be the primary driver of global change impacts on kingfish early life history; however, elevated pCO2 could affect critical aspects of swimming performance in this pelagic species. Our findings will help parameterise and structure fisheries population dynamics models and improve projections of impacts to large pelagic fishes under climate change scenarios to better inform adaptation and mitigation responses. PMID- 29790238 TI - Personal sleep debt and daytime sleepiness mediate the relationship between sleep and mental health outcomes in young adults. AB - BACKGROUND: Sleep duration and chronotype (i.e., morningness-eveningness) are associated with increased depression and anxiety risk, but differences in individual sleep need and lifestyle may mean these sleep parameters do not present the same risk across all individuals. This study explored the mediating role of sleep debt and daytime sleepiness in the relationship between sleep and mental health symptoms in young adults, a particularly vulnerable population. METHODS: Young adult university students (n = 2,218) and young adults from the general population in the United States (n = 992) provided estimates of actual and optimal sleep duration, and completed validated measures of sleepiness, chronotype, and depression and anxiety risk. Mediation models examining sleepiness and sleep debt (i.e., difference between optimal and actual sleep) as parallel mediators were tested. RESULTS: Sleepiness and sleep debt mediated the relationship between short sleep and depression and anxiety risk in the university sample, while sleepiness mediated these relationships in the general population sample. Sleepiness and sleep debt also mediated the impact of evening type preferences on depression and anxiety risk in university students, but no mediation of this effect was found in young adults from the general population. CONCLUSIONS: This study reports potential mediating mechanisms related to the increased mental health risk conferred by short sleep and evening chronotype. These results have implications for how primary care physicians assess psychopathology risk, arguing for a focus on the assessment of daytime sleepiness and sleep debt in university populations, while for young adults in the general population, these factors may be less important. PMID- 29790240 TI - Understanding mucosal and microbial functionality of the female reproductive tract by metaproteomics: Implications for HIV transmission. AB - The mucosal surface of the female genital tract contains physiological, immunological, and microbial components that collectively comprise a functioning "mucosal system" that is critical for reproductive health. Alterations or imbalances to any of these components can have significant consequences for susceptibility to sexually transmitted infections, such as HIV. In recent years the advent of advanced systems biology technologies, such as metaproteomics, has provided new toolsets to studying mucosal systems. Studies have linked an altered mucosal proteome to many HIV risk factors including mucosal inflammation, bacterial vaginosis, hormonal contraceptives, and reduced efficacy of antiretroviral drugs for HIV prevention. Herein we will discuss how metaproteomics has been used to study mucosal system components, including epithelial barriers, inflammation, and the microbiome, with a focus on what alterations may contribute to increased HIV transmission risk in women. PMID- 29790241 TI - Maternal education and childhood immunization in Turkey. AB - We study the causal effect of maternal education on childhood immunization rates. We use the Compulsory Education Law of 1997, and the differentiation in its implementation across regions, as instruments for schooling of young mothers in Turkey. The Compulsory Education Law increased the compulsory years of schooling of those born after 1986 from 5 to 8 years. We find that education of mothers increases the probability of completing the full course of diphtheria, pertussis, and tetanus and Hepatitis B vaccinations for their children. The results are robust to variations in regression specification and including various individual and community variables. PMID- 29790242 TI - Looking for trouble? Diagnostics expanding disease and producing patients. AB - Novel tests give great opportunities for earlier and more precise diagnostics. At the same time, new tests expand disease, produce patients, and cause unnecessary harm in overdiagnosis and overtreatment. How can we evaluate diagnostics to obtain the benefits and avoid harm? One way is to pay close attention to the diagnostic process and its core concepts. Doing so reveals 3 errors that expand disease and increase overdiagnosis. The first error is to decouple diagnostics from harm, eg, by diagnosing insignificant conditions. The second error is to bypass proper validation of the relationship between test indicator and disease, eg, by introducing biomarkers for Alzheimer's disease before the tests are properly validated. The third error is to couple the name of disease to insignificant or indecisive indicators, eg, by lending the cancer name to preconditions, such as ductal carcinoma in situ. We need to avoid these errors to promote beneficial testing, bar harmful diagnostics, and evade unwarranted expansion of disease. Accordingly, we must stop identifying and testing for conditions that are only remotely associated with harm. We need more stringent verification of tests, and we must avoid naming indicators and indicative conditions after diseases. If not, we will end like ancient tragic heroes, succumbing because of our very best abilities. PMID- 29790244 TI - Relapsing acute disseminated encephalomyelitis followed by optic neuritis in children; a clinical entity associated with anti-MOG antibody. PMID- 29790243 TI - Identifying language impairment in bilingual children in France and in Germany. AB - BACKGROUND: The detection of specific language impairment (SLI) in children growing up bilingually presents particular challenges for clinicians. Non-word repetition (NWR) and sentence repetition (SR) tasks have proven to be the most accurate diagnostic tools for monolingual populations, raising the question of the extent of their usefulness in different bilingual populations. AIMS: To determine the diagnostic accuracy of NWR and SR tasks that incorporate phonological/syntactic complexity as discussed in recent linguistic theory. The tasks were developed as part of the Language Impairment Testing in Multilingual Settings (LITMUS) toolkit, in two different national settings, France and Germany, and investigated children with three different home languages: Arabic, Portuguese and Turkish. METHODS & PROCEDURES: NWR and SR tasks developed in parallel were administered to 151 bilingual children, aged 5;6-8;11, in France and in Germany, to 64 children in speech-language therapy (SLT) and to 87 children not in SLT, whose first language (L1) was Arabic, Portuguese or Turkish. Children were also administered standardized language tests in each of their languages to determine likely clinical status (typical development (TD) or SLI), and parents responded to a questionnaire including questions about early and current language use (bilingualism factors) and early language development (risk factors for SLI). Monolingual controls included 47 TD children and 29 children with SLI. Results were subjected to inter-group comparisons, to diagnostic accuracy calculation, and to correlation and multiple regression analyses. OUTCOMES & RESULTS: In accordance with previous studies, NWR and SR identified SLI in the monolingual children, yielding good to excellent diagnostic accuracy. Diagnostic accuracy in bilingual children was fair to good, generally distinguishing children likely to have SLI from children likely to have TD. Accuracy was necessarily linked to the determination of clinical status, which was based on standardized assessment in each of the child's languages. Positive early development, a composite risk factor for SLI, and not variables related to language exposure and use, generally emerged as the strongest predictor of performance on the two tasks, constituting additional, independent support for the efficacy of NWR and SR in identifying impairment in bilingual children. CONCLUSIONS & IMPLICATIONS: NWR and SR tasks informed by linguistic theory are appropriate for use as part of the diagnostic process for identifying language impairment in bilingual children for whom the language of assessment is different from the home language, in diverse sociolinguistic contexts. PMID- 29790245 TI - P465L-PPARgamma mutation confers partial resistance to the hypolipidaemic action of fibrates. AB - AIMS: Familial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPARgamma. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated with this mutation using a humanized mouse model that recapitulates most of the clinical symptoms observed in patients who have been phenotyped under different experimental conditions. One of the key clinical manifestations observed, both in humans and mouse models, is the ectopic accumulation of fat in the liver. With this study we aim to dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterize the negative effect of this PPARgamma mutation on the activity of PPARalpha in vivo when activated by fibrates. MATERIAL AND METHODS: P465L-PPAR mutant and wild-type mice were divided into 8 experimental groups, 4 different conditions per genotype. Briefly, mice were fed a chow diet or a high-fat diet (HFD 45% Kcal from fat) for a period of 28 days and treated with WY14643 or vehicle for five days before culling. At the end of the experiment, tissues and plasma were collected. We performed extensive gene expression, fatty acid composition and histological analysis in the livers. The serum collected was used to measure several metabolites and to perform basic lipoprotein profile. RESULTS: P465L mice showed increased levels of insulin and free fatty acids (FFA) as well as increased liver steatosis. They also exhibit decreased levels of very low density lipoproteins (VLDL) when fed an HFD. We also provide evidence of impaired expression of a number of well-established PPARalpha target genes in the P465L mutant livers. CONCLUSION: Our data demonstrate that P465L confers partial resistance to the hypolipidemic action of fibrates. These results show that the fatty liver phenotype observed in P465L mutant mice is not only the consequence of dysfunctional adipose tissue, but also involves defective liver metabolism. All in all, the deleterious effects of P465L-PPARgamma mutation may be magnified by their collateral negative effect on PPARalpha function. PMID- 29790246 TI - A review of predation as a limiting factor for bird populations in mesopredator rich landscapes: a case study of the UK. AB - The impact of increasing vertebrate predator numbers on bird populations is widely debated among the general public, game managers and conservationists across Europe. However, there are few systematic reviews of whether predation limits the population sizes of European bird species. Views on the impacts of predation are particularly polarised in the UK, probably because the UK has a globally exceptional culture of intensive, high-yield gamebird management where predator removal is the norm. In addition, most apex predators have been exterminated or much depleted in numbers, contributing to a widely held perception that the UK has high numbers of mesopredators. This has resulted in many high-quality studies of mesopredator impacts over several decades. Here we present results from a systematic review of predator trends and abundance, and assess whether predation limits the population sizes of 90 bird species in the UK. Our results confirm that the generalist predators Red Fox (Vulpes vulpes) and Crows (Corvus corone and C. cornix) occur at high densities in the UK compared with other European countries. In addition, some avian and mammalian predators have increased numerically in the UK during recent decades. Despite these high and increasing densities of predators, we found little evidence that predation limits populations of pigeons, woodpeckers and passerines, whereas evidence suggests that ground-nesting seabirds, waders and gamebirds can be limited by predation. Using life-history characteristics of prey species, we found that mainly long-lived species with high adult survival and late onset of breeding were limited by predation. Single-brooded species were also more likely to be limited by predation than multi-brooded species. Predators that depredate prey species during all life stages (i.e. from nest to adult stages) limited prey numbers more than predators that depredated only specific life stages (e.g. solely during the nest phase). The Red Fox and non-native mammals (e.g. the American Mink Neovison vison) were frequently identified as numerically limiting their prey species. Our review has identified predator-prey interactions that are particularly likely to result in population declines of prey species. In the short term, traditional predator-management techniques (e.g. lethal control or fencing to reduce predation by a small number of predator species) could be used to protect these vulnerable species. However, as these techniques are costly and time-consuming, we advocate that future research should identify land-use practices and landscape configurations that would reduce predator numbers and predation rates. PMID- 29790247 TI - The promotion of tissue engineering blood vessel patency by CGS21680 through regulating pro-inflammatory activities of endothelial progenitor cell. AB - The mobilization and homing of endothelial progenitor cells (EPCs) contribute to the rapid endothelialization of tissue engineering blood vessel (TEBV). Inflammation can affect TEBV patency, and monocytes/macrophages (MM) are the main effector cells. But it is not clear how EPCs interact with MM after TEBV transplantation. Our results showed acellular materials would not directly cause acute and severe inflammatory responses but activate E-selectin expression in homing EPCs, gradually promoting the polarization of MM to the M1. Adenosine A2a receptor agonist CGS21680 promoted the secretion of more proangiogenic factors from MM, inducing EPC migration and mobilization. CGS21680 could inhibit MM polarization to the M1 type through the down-regulation of EPC proinflammatory molecules, such as E-selectin. Chitosan/(2-hydroxypropyl)-beta-cyclodextrin nanoparticles were prepared to control the release of CGS-21680 and then modified to TEBVs through layer-by-layer assembly. Animal experiments showed that this TEBV can maintain patency for 6 months and good endothelialization was observed. In summary, our results showed the regulation of EPC pro-inflammatory activities is a new approach to enhance TEBV patency. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2634-2642, 2018. PMID- 29790248 TI - Diagnosis and management of conductive hearing loss in children with trisomy 21. AB - AIM: The objective of this study is to review the prevalence and degree of hearing loss in children with trisomy 21, their response to intervention and the presence of concomitant pathologies. The project will also highlight the experiences of the children from their parents' and guardians' perspective and the link between perceived service quality and an objective improvement in their hearing after rehabilitation. METHODS: All patients with trisomy 21 who were referred to district general otolaryngology outpatient clinics between 2014 and 2016 were included. A retrospective analysis of the medical notes and audiograms along with a qualitative questionnaire to the children's parents was utilised to gather the information. RESULTS: The study showed that 77% (17/22) of children suffered from hearing loss, with a moderate degree being most prevalent. The majority of patients (14/17, 82%) were managed conservatively, undergoing a period of watchful waiting (9/17, 53%) or receiving hearing aids (5/17, 30%) and 3 of 17 (17%) were managed with grommet insertion. The improvement in hearing with hearing aids was comparable with grommet insertion and hearing aids scored highest in the post-intervention qualitative assessment with grommet insertion scoring the lowest. CONCLUSIONS: Functional hearing has been shown to be key in developing speech and language skills. In children with trisomy 21, behavioural and anatomical abnormalities make the diagnosis and intervention technically more challenging. This study demonstrates that in the absence of other otological symptoms, hearing loss can be managed effectively and with the least distress to the children with hearing aids. PMID- 29790249 TI - The mechanisms of epigenetic inheritance: how diverse are they? AB - Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence. These mechanisms include (i) regulation of transcription by DNA methylation, histone modifications, and transcription factors, (ii) RNA splicing, (iii) RNA-mediated post-transcriptional silencing, (iv) organellar translation, (v) protein processing by truncation, (vi) post translational chemical modifications, (vii) protein folding, and (viii) homologous and non-homologous protein interactions. The breadth of this list suggests that any or almost any regulatory mechanism that participates in gene expression or gene-product functioning, under certain circumstances, may produce EI. Although the modes of EI are highly variable, in many epigenetic systems, stable allelic variants can be distinguished. Irrespective of their nature, all such alleles have an underlying similarity: each is a bimodular hereditary unit, whose features depend on (i) a certain epigenetic mark (epigenetic determinant) in the DNA sequence or its product, and (ii) the DNA sequence itself (DNA determinant; if this is absent, the epigenetic allele fails to perpetuate). Thus, stable allelic epigenetic inheritance (SAEI) does not contradict the hereditary role of DNA, but involves additional molecular mechanisms with no or almost no limitations to their variety. PMID- 29790250 TI - Photochemical Construction of Carbonitride Structures for Red-Light Redox Catalysis. AB - Metal-free carbonitride(CN) semiconductors are appealing light-transducers for photocatalytic redox reactions owing to the unique band gap and stability. To harness solar energy efficiently, CN catalysts that are active over a wider range of the visible spectrum are desired. Now a photochemical approach has been used to prepare a new-type triazine-based CN structure. The obtained CN shows extraordinary light-harvesting characteristics, with suitable semiconductor-redox potentials. The light absorption edge of the CN reaches up to 735 nm, which is significantly longer than that of the conventional CN semiconductor at about 460 nm. As expected, the CN can efficiently catalyze oxidation of alcohols and reduction of CO2 with visible light, even under red-light irradiation. The results represent an important step toward the development of red-light responsive triazine-based structures for solar applications. PMID- 29790251 TI - Chitosan/biphasic calcium phosphate scaffolds functionalized with BMP-2 encapsulated nanoparticles and RGD for bone regeneration. AB - Advancements in bone tissue engineering require the improvement of tissue scaffolds, which should not only exhibit suitable mechanical properties and highly porous structures, but also effectively carry signaling molecules that can mediate bone formation and tissue regeneration. In the present study, we established chitosan/biphasic calcium phosphate (CS/BCP) scaffolds functionalized with Arg-Gly-Asp (RGD) and BMP-2-loaded nanoparticles. The resulting scaffolds were highly similar to natural bone extracellular matrix (ECM) in terms of composition and structural properties. First, we synthesized CS/BCP composite bionic scaffolds via the freeze-drying method. Then, RGD peptides were covalently conjugated onto the scaffolds via the EDC/NHS method. The BMP-2-encapsulated BSA nanoparticles were prepared via a desolvation method and then coated with CS and oxidized alginate to achieve sustained release of BMP-2. In vitro cell culture and in vivo implantation tests confirmed that RGD and BMP-2 synergistically enhanced cell attachment and spreading by providing integrin binding surface and facilitating osteogenic differentiation. In summary, the bioceramic/biopolymer scaffolds functionalized with signaling biomolecules successfully provided a favorable microenvironment for bone formation and thus serve as potential candidates for use in bone tissue engineering. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2613-2624, 2018. PMID- 29790252 TI - Should we still be utilizing warfarin in the type 2 diabetic patient? AB - The frequency of non-valvular atrial fibrillation is increased by 40% in type 2 diabetic individuals and the thromboembolic risk associated with atrial fibrillation is increased by 79% compared with the non-diabetic individual with atrial fibrillation. Warfarin, the traditional anticoagulant used to prevent thromboembolism, is non-specific and affects several proteins outside the coagulation system. Decreasing the levels of matrix Gla protein entails an increase in coronary and renal artery calcification, which has the potential to increase cardiovascular events and accelerate decline in renal function. The direct-acting oral anticoagulants are specific, directly inhibiting either thrombin or factor Xa, and have been shown to be safer and more efficacious in studies of the type 2 diabetic patient. PMID- 29790253 TI - Robotic left colectomy with complete mesocolectomy for splenic flexure and descending colon cancer, compared with a laparoscopic procedure. AB - BACKGROUND: Its relatively low incidence and its surgical complexity mean that a standardized technique for left colectomy has not yet been established for splenic flexure and descending colon cancer (SF-DCC). METHODS: Seventy-three patients (robot-assisted left colectomy with complete mesocolectomy [R-LCCM], n = 20; laparoscopic left colectomy with complete mesocolectomy [L-LCCM], n = 53) with SF-DCC were enrolled at the Asan Medical Center (Seoul, Korea). RESULTS: R LCCM conveniently enables dexterous dissection for the multi-directional approaches during left mesocolic mobilization. A conversion to open surgery was required in two patients of the L-LCCM group, but not in the R-LCCM group. A positive circumferential resection margin was exclusively identified in two patients in the L-LCCM group. Mean lymph node harvest was 21 with no difference between the two groups. CONCLUSIONS: Although R-LCCM provided few remarkable advantages over L-LCCM, it could be considered as an efficient approach in patients with SF-DCC. PMID- 29790254 TI - Chemsex and new HIV diagnosis in gay, bisexual and other men who have sex with men attending sexual health clinics. AB - OBJECTIVES: The aim of the study was to analyse associations between chemsex and new HIV and sexually transmitted infection (STI) diagnoses among gay, bisexual and other men who have sex with men (GBMSM) accessing sexual health clinics. METHODS: A retrospective case note review was carried out for all GBMSM attending two London sexual health clinics between 1 June 2014 and 31 July 2015. RESULTS: Chemsex status was documented for 1734 of 1840 patients. Overall, 27.1% (n = 463) disclosed current recreational drug use, of whom 286 (16.5%) disclosed chemsex participation and 74 of 409 (18.1%) injected drugs. GBMSM who were already HIV positive were more likely to disclose chemsex participation [adjusted odds ratio (AOR) 2.55; 95% confidence interval (CI) 1.89-3.44; P < 0.001]. Those disclosing chemsex participation had higher odds of being newly diagnosed with HIV infection (AOR 5.06; 95% CI 2.56-10.02; P < 0.001), acute bacterial STIs (AOR 3.94; 95% CI 3.00-5.17; P < 0.001), rectal STIs (AOR 4.45; 95% CI 3.37-6.06; P < 0.001) and hepatitis C (AOR 9.16; 95% CI 2.31-36.27; P = 0.002). HIV-negative chemsex participants were also more likely to have accessed post-exposure prophylaxis for HIV in the study period and to report sex with a discordant HIV- or hepatitis C virus-infected partner (P < 0.001). CONCLUSIONS: Chemsex disclosure in sexual health settings is associated with higher rates of STI diagnoses, including HIV infection and hepatitis C. GBMSM attending sexual health services should therefore be assessed for chemsex participation and disclosure should prompt health promotion, harm minimization and wellbeing interventions. PMID- 29790255 TI - Risk of major congenital malformations following first-trimester exposure to vaginal azoles used for treating vulvovaginal candidiasis: a population-based retrospective cohort study. AB - OBJECTIVE: To evaluate the risk for major malformations following first-trimester exposure to vaginal azoles. DESIGN: A population-based retrospective cohort study of women exposed to vaginal azoles from the first day of the last menstrual period until the 90th gestational day. SETTING: A combination of four computerised databases: medications, birth, infant hospitalizations, and pregnancy terminations. POPULATION: All women who gave birth or underwent a pregnancy termination at Soroka Medical Center, Beer-Sheva, Israel, between 1999 and 2009. METHODS: Crude and adjusted relative risks for major congenital malformations and for specific malformations according to organ systems were calculated using a multivariate negative binomial regression. Potential confounders were assessed and controlled for included parity, maternal age, ethnicity, maternal diabetes, smoking, and year of birth or pregnancy termination. Additional analysis using propensity score matching was performed for selected malformations. MAIN OUTCOME MEASURES: Major malformations as well as specific malformations according to organ systems. RESULTS: Of 101 615 pregnancies, 1993 (1.96%) were exposed to clotrimazole vaginal tablets and 313 (0.31%) to miconazole vaginal tablets during the first trimester of pregnancy. No association was found between first-trimester exposure to clotrimazole and major or specific malformations. An association was found between miconazole exposure and musculoskeletal malformation in general and other congenital musculoskeletal anomalies in particular. However, no association was detected when propensity score matching was used. CONCLUSIONS: Intrauterine exposure to vaginal azoles during the first trimester of pregnancy was not associated with either major or specific malformations according to organ systems. TWEETABLE ABSTRACT: First trimester exposure to vaginal azoles is not associated with either major or specific malformations. PMID- 29790256 TI - Platelet characteristics in patients with essential thrombocytosis. AB - BACKGROUND: Essential thrombocytosis (ET) is a myeloproliferative disorder characterized by an increased platelet count. ET is associated with an increased risk of thrombosis, and procoagulant features of the disease may include an increased number of reactive reticulated platelets and an increased aggregation potential. We aimed to explore the association between platelet count, platelet turnover, and platelet aggregation in patients with ET. METHODS: We included 24 ET patients who discontinued antiplatelet therapy prior to blood sampling. Reticulated platelets were assessed as immature platelet count (IPC) and immature platelet fraction by automated flow cytometry (Sysmex XE-5000). Platelet aggregation was investigated by impedance aggregometry (Multiplate(r) Analyzer) and aggregation potential by flow cytometry (NAVIOS). RESULTS: Our results showed that ET patients had increased IPC compared to healthy individuals (median 12.3 vs. median 6.9, P < 0.0001). Furthermore, a positive correlation between platelet count and impedance aggregation was demonstrated using arachidonic acid (r = 0.48, P = 0.02), thrombin-receptor-activating-peptide (r = 0.46, P = 0.03) and adenosine diphosphate (r = 0.56, P = 0.007) as agonists. Finally, an increased aggregation potential was demonstrated in ET patients compared to healthy individuals. CONCLUSIONS: The study showed that ET patients compared to healthy individuals have an increased amount of reticulated platelets and increased aggregation potential. These findings might in part explain the increased thromboembolic risk in patients with ET. (c) 2018 International Clinical Cytometry Society. PMID- 29790257 TI - Functionalized silk fibers from transgenic silkworms for wound healing applications: Surface presentation of bioactive epidermal growth factor. AB - Growth factors play a crucial role in wound healing in general and are promising tools for the treatment of chronic wounds as they can restore the physiological wound healing process. In growth factor-loaded wound dressings, human epidermal growth factor (EGF) is released in a burst and washed out quickly. The developed matrix consists of recombinant EGF produced in transgenic silkworms as a fusion protein with the fibroin light chain. The covalent linkage prevents EGF from draining into the surrounding tissue while presenting the growth factor on the surface. EGF-functionalized silk membranes and nonwovens lead to a 2.5-fold increase in the cell number of fibroblasts, while retaining full bioactivity even after e-beam sterilization. EGF is long-term presented without burst release and significantly reduces the wound area by 15% in an in vitro wound model. Hence, the cost-effective production of a biomaterial using transgenic silkworm larvae in combination with a growth factor paves the way for a promising new multifactorial wound cover for chronic wound healing. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2643-2652, 2018. PMID- 29790258 TI - Distinguishing immunohistochemical features of alopecia areata from androgenic alopecia. AB - BACKGROUND: Distinction between alopecia areata (AA) and androgenic alopecia (AGA) can be made according to clinical presentation and biopsy findings. However, it is sometimes difficult to differentiate them, especially when the diffuse pattern of both AA and AGA is in the differential diagnosis of hair loss in androgen-dependent areas. OBJECTIVES: To evaluate the characteristics of inflammatory cell infiltration using CD3, CD4, CD8, and CD20 antigens, in AA and AGA to find some consistent histological clues for distinguishing these two entities. METHODS: A retrospective analysis of patients with diagnosed AA (30 cases) and AGA (30 cases) was performed based on the clinical and histopathological criteria. We studied immunohistochemical findings for CD3, CD4, CD8, and CD20 in all selected cases. RESULTS: Immunohistochemical stains for CD4 and CD20 were not helpful in differentiating AA from AGA, but the inflammation density for AA was significantly (P-value = .025, .001) higher than AGA in CD3 (specificity= 86.7% and sensitivity= 96.7%) and CD8 (specificity= 50% and sensitivity=86.6%). Our findings revealed that intrafollicular CD3 (P-value = .017) and CD8 (P-value = ?.001) infiltrations were significantly higher in AA samples in comparison with AGA. CONCLUSION: Characterization of CD3 and CD8 in IHC samples is helpful, especially when the density of CD3 and CD8 T cells are significant in more than 50% of the infiltrated cells and are located intrafolliculary. Moreover, the most specific and sensitive test for differentiating of AA from AGA is CD3. PMID- 29790259 TI - Monitoring and evaluation framework for hypertension programs. A collaboration between the Pan American Health Organization and World Hypertension League. AB - The Pan American Health Organization (PAHO)-World Hypertension League (WHL) Hypertension Monitoring and Evaluation Framework is summarized. Standardized indicators are provided for monitoring and evaluating national or subnational hypertension control programs. Five core indicators from the World Health Organization hearts initiative and a single PAHO-WHL core indicator are recommended to be used in all hypertension control programs. In addition, hypertension control programs are encouraged to select from 14 optional qualitative and 33 quantitative indicators to facilitate progress towards enhanced hypertension control. The intention is for hypertension programs to select quantitative indicators based on the current surveillance mechanisms that are available and what is feasible and to use the framework process indicators as a guide to program management. Programs may wish to increase or refine the number of indicators they use over time. With adaption the indicators can also be implemented at a community or clinic level. The standardized indicators are being pilot tested in Cuba, Colombia, Chile, and Barbados. PMID- 29790260 TI - Endogenous GLP-1 alters postprandial functional connectivity between homeostatic and reward-related brain regions involved in regulation of appetite in healthy lean males: A pilotstudy. AB - AIMS: Peripheral infusion of glucagon-like peptide-1 (GLP-1) can affect brain activity in areas involved in the regulation of appetite, including hypothalamic and reward-related brain regions. In contrast, the physiological role of endogenous GLP-1 in the central regulation of appetite has hardly been investigated. MATERIALS AND METHODS: This was a randomized, cross-over trial that involved 12 healthy volunteers who received an intragastric (ig) glucose (gluc) load, with or without intravenous (iv) exendin9-39 (ex9-39; specific GLP-1 receptor antagonist). Functional magnetic resonance imaging was used to investigate the effect of endogenous GLP-1 on resting state functional connectivity (rsFC) between homeostatic and reward-related brain regions. Visual analogue scales were used to rate appetite-related sensations. Blood samples were collected for GI hormone measurements. RESULTS: Administration of iv-ex9-39/ig gluc induced a significantly higher rsFC, relative to ig-gluc administration, between the hypothalamus and the left lateral orbitofrontal cortex (OFC) as well as the left amygdala (P <= .001, respectively). Administration of iv-ex9-39/ig gluc induced a significantly higher rsFC, relative to ig-gluc administration, between the right nucleus accumbens and the right lateral OFC (P < .001). Administration of iv-ex9-39/ig-gluc induced a significantly lower rsFC, relative to ig-gluc administration, between the midbrain and the right caudate nucleus (P = .001). Administration of ig-gluc significantly decreased prospective food consumption and increased sensations of fullness compared to pre-infusion baseline (P = .028 and P = .019, respectively); these effects were not present in the iv-ex9-39/ig-gluc condition. CONCLUSIONS: This pilot trial provides preliminary experimental evidence that glucose-induced endogenous GLP-1 affects central regulation of appetite by modulating rsFC in homeostatic and reward related brain regions in healthy lean male participants in a GLP-1 receptor mediated fashion. PMID- 29790261 TI - "Characterization of ELEKTA SRS cone collimator using high spatial resolution monolithic silicon detector array". AB - PURPOSE: To investigate the accuracy of the dosimetry of radiation fields produced by small ELEKTA cone collimators used for stereotactic radiosurgery treatments (SRS) using commercially available detectors EBT3 GafchromicTM film, IBA Stereotactic diode (SFD), and the recently developed detector DUO, which is a monolithic silicon orthogonal linear diode array detector. METHODS: These three detectors were used for the measurement of beam profiles, output factors, and percentage depth dose for SRS cone collimators with cone sizes ranging from 5 to 50 mm diameter. The measurements were performed at 10 cm depth and 90 cm SSD. RESULTS: The SRS cone beam profiles measured with DUO, EBT3 film, and IBA SFD agreed well, results being in agreement within +/-0.5 mm in the FWHM, and +/-0.7 mm in the penumbra region. The output factor measured by DUO with 0.5 mm air gap above agrees within +/-1% with EBT3. The OF measured by IBA SFD (corrected for the over-response) agreed with both EBT3 and DUO within +/-2%. All three detectors agree within +/-2% for PDD measurements for all SRS cones. CONCLUSIONS: The characteristics of the ELEKTA SRS cone collimator have been evaluated by using a monolithic silicon high spatial resolution detector DUO, EBT3, and IBA SFD diode. The DUO detector is suitable for fast real-time quality assurance dosimetry in small radiation fields typical for SRS/SRT. This has been demonstrated by its good agreement of measured doses with EBT 3 films. PMID- 29790262 TI - The efficacy and tolerability of 5-aminolevulinic acid 5% thermosetting gel photodynamic therapy (PDT) in the treatment of mild-to-moderate acne vulgaris. A two-center, prospective assessor-blinded, proof-of-concept study. AB - BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease, commonly treated with topical or systemic drugs, according to the severity of the condition. Retinoids and antibiotic compounds are considered cornerstone approaches in this condition. However, low adherence to the therapy and the issue of bacterial resistance undermine the efficacy in the long term. Photodynamic therapy (PDT) with 20% aminolevulinic acid (ALA) has shown to be effective in the treatment of inflammatory acne. Skin tolerability, however, could be a limiting factor for a widespread use of this approach. A new formulation of 5% ALA in thermosetting gel has been recently available. This formulation allows a more convenient application procedure without occlusion and better and more efficient release of the active compound in comparison with traditional ALA formulations like creams or ointments. STUDY AIM: To evaluate in a two-center, assessor blinded, prospective, proof-of-concept study, the efficacy, and tolerability of red-light (630 nm) PDT with a new 5-ALA "low-dose" topical gel formulation (5%) in the treatment of inflammatory mild-to-moderate acne vulgaris (AV). SUBJECTS AND METHODS: A total of 35 subjects with moderate AV of the face (mean age: 24 +/ 8 years, 13 men and 22 women) were enrolled, after their written informed consent. The primary outcome was the evolution of GAG (Global Acne Grade System) score at baseline and after an average of three, 630-nm, 15-minute, PDT sessions, performed every 2 weeks. GAG score was also calculated in a follow-up visit 6 months after the last PDT session. Skin tolerability was assessed during PDT sessions with a patient-reported discomfort level evaluation score from 0 (no discomfort at all) to 3 (severe discomfort). RESULTS: At baseline, the GAG score was 21 +/- 6. After the last PDT session, the GAG score evaluated in a blinded fashion (digital photographs) was significantly reduced to 6.5 +/- 5.7, representing a 70% reduction (P = .0001, Wilcoxon test; mean difference 14.9; 95% CI of the difference: 12.1-17.6). At the follow-up visit, the GAG score was 6.7 +/- 6.8. The 5% ALA thermosetting gel Red-light PDT was in general very well tolerated with a discomfort mean level score of 0.5 +/- 1. CONCLUSION: This proof of-concept study supports the efficacy of 5% ALA thermosetting gel red-light PDT in inflammatory acne of the face with a relevant clinical improvement of inflammatory lesions with a very good tolerability profile. Clinical improvement was maintained in the medium term (Trial Registration Number: ISRCTN66066651). PMID- 29790263 TI - Herbicide hormesis can act as a driver of resistance evolution in weeds - PSII target site resistance in Chenopodium album L. as a case study. AB - BACKGROUND: Herbicide hormesis may play a role in the evolution of weed resistance by increasing resistance selection. A standard herbicide rate may be subtoxic to resistant plants and make them more fit than untreated plants. If this increase in fitness is ultimately expressed in reproductive traits, resistance genes can accumulate more rapidly and exacerbate resistance evolution by magnifying the selection differential between resistant and sensitive plants. The hypothesis of hormetically enhanced reproductive fitness was studied for a photosystem II (PSII) target-site resistant (TSR) biotype of Chenopodium album exposed to the triazinone metamitron in comparison with its wild-type. RESULTS: Both biotypes showed an initial hormetic growth increase at different doses leading to fitness enhancements of between 19% and 61% above untreated plants. However, hormetic effects only resulted in higher fitness at maturity in resistant plants with a maximum stimulation in seed yield of 45% above untreated plants. Applying realistic metamitron rates, reproductive fitness of resistant plants was increased by 15-32%. CONCLUSIONS: Agronomically relevant doses of metamitron induced considerable hormesis in a PSII-TSR C. album genotype leading to enhanced relative fitness through reproductive maturity. This increase in relative fitness suggests an impact on resistance selection and can compensate for the oft-reported fitness costs of the mutation studied. Field rates of herbicides can, thus, not only select for resistant plants, but also enhance their reproductive fitness. The finding that herbicide hormesis can be eco evolutionary important may have important implications for understanding the evolution of herbicide resistance in weeds. (c) 2018 Society of Chemical Industry. PMID- 29790264 TI - Immune responses against tumour-associated antigen-derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients. AB - BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumour-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR). CTL responses against 38 TAA-derived epitopes were measured using samples from 26 cholangiocarcinoma patients by interferon-gamma enzyme linked immunospot (ELISPOT)-assay. RESULTS: Most TAAs were expressed in cholangiocarcinoma cell lines and specimens in PCR. Epitopes that stimulated a specific immune response were defined as those that elicited a CTL response in more than 3 patients and little response in healthy volunteers, as measured by ELISPOT-assay. Based on these criteria, there were 18 epitopes that stimulated specific immune responses: squamous cell carcinoma antigen recognized by T cells (SART)1690 , P53161 , multidrug resistance-associated protein (MRP)3503 , Survivin2B80 , melanoma associated antigen (MAGE)-A4143 , receptor tyrosine kinase ErbB-2/neu (Her2/neu)63 , Wilms tumour (WT1)235 , WT1417 , beta-catenin29 , carcinoembryonic antigen (CEA)268 , CEA652 , epithelial cell adhesion molecule (EpCAM)173 , enhancer of zeste homolog (EZH)2291 , mucin 5AC (MUC5AC)716 , glypican-3 (GPC3)298 and kinesin family member 20A (KIF20A)66 . Furthermore, the absolute number of lymphocytes in peripheral blood was significantly correlated with the TAA-specific response. Lastly, the overall survival was significantly prolonged in patients with 2 or more TAA-specific CTL responses compared with none to one. CONCLUSIONS: These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. PMID- 29790265 TI - Lipid-lowering medication is associated with decreased risk of diabetic retinopathy and the need for treatment in patients with type 2 diabetes: A real world observational analysis of a health claims database. AB - AIMS: Fenofibrate and statins reduced the need for diabetic retinopathy (DR) related treatment in clinical trials. We aimed to determine whether use of lipid lowering medication reduces the risk of DR and the need for treatment in patients with type 2 diabetes using a real-world health claims database. METHODS: This was an observational analysis using a nation-wide health claims database of the Japan Medical Data Center (JMDC). Type 2 diabetes was defined according to ICD-10 codes for use of glucose-lowering medication. Use of lipid-lowering medication for at least 1 year was confirmed by the Anatomical Therapeutic Chemical Classification System. DR and diabetic macular edema (DME) were determined by ICD-10 codes. DR related treatments were determined by health insurance claims. A propensity score for use of lipid-lowering medication was estimated, and a doubly robust estimator, using the inverse probability weighting model with regression adjustment, was obtained to determine odds ratios (OR) with 95% confidence interval (95% CI) for cumulative incidence of DR and its treatments over 3 years. RESULTS: There were 69 070 individuals with type 2 diabetes at baseline, among whom DR developed in 5687 over a period of 3 years. Use of lipid-lowering medication was associated with decreased risk of incidence of DR (OR, 0.772; 95% CI, 0.720-0.827; P < .001). Use of lipid-lowering medication was also associated with decreased incidence of DME, any treatments for DR, laser photocoagulation and vitrectomy in patients with DR at baseline. CONCLUSIONS: In a population of patients with type 2 diabetes with a variety of risk profiles, use of lipid lowering medication reduced the risk of DR and thus the risks involved in treatment with laser photocoagulation and vitrectomy. PMID- 29790266 TI - Clindamycin to reduce preterm birth in a low resource setting: a randomised placebo-controlled clinical trial. AB - OBJECTIVE: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH >=5.0. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: Rural southern India. POPULATION: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (>=5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death. CONCLUSION: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH >=5.0. TWEETABLE ABSTRACT: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH >=5.0. PMID- 29790267 TI - Systematic review of platelet-rich plasma (PRP) preparation and composition for the treatment of androgenetic alopecia. AB - BACKGROUND: Platelet-rich plasma (PRP) injections have gained popularity in dermatology practice as a treatment for hair loss. As an autologous blood product, PRP is categorized as a minimally manipulated tissue by the U.S. Food and Drug Administration (FDA) and thus evades extensive regulation. As a result, there is a lack of standardization of its preparation and final composition. OBJECTIVE: This study aims to provide a systematic review of the various PRP preparation protocols and PRP compositions utilized in clinical trials for the treatment of hair loss. METHODS & MATERIALS: A review of the literature was performed using PubMed and Ovid/Medline in November 2017 using the search terms "Platelet-Rich Plasma" and ("Alopecia" or "Hair Loss"), including all publication dates. Human clinical trials in the English language were included. RESULTS: Nineteen studies (in 15 articles) met the inclusion criteria for analysis. Only 21% of these studies reported all PRP preparation factors analyzed, and only 32% of the protocols reported the platelet count for both the initial whole blood and final PRP product. CONCLUSION: The current reporting of PRP preparation methodology and final composition is inconsistent and insufficient to enable comparison between studies and determination of efficacy for particular treatment applications. PMID- 29790268 TI - Ask me: Children's experiences of pain explored using the draw, write, and tell method. AB - PURPOSE: Pain management within emergency departments (ED) remains challenging. Given that unrelieved pain in children is linked to a number of negative physiological and psychological consequences, optimal management of children's pain is paramount. Many studies exploring children's pain have adopted quantitative methods or sought the perspectives of adults. Compared to adults, studies examining children's views on pain and pain management are limited. This study aimed to explore children's pain experiences, their perception of pain management and expectations of the role of the nurse. DESIGN: This was a qualitative descriptive study using an inductive approach. METHODS: Fifteen children, aged 4-8 years who presented to the ED of an Australian tertiary pediatric hospital in acute pain participated. Data were collected using draw, write, and tell (DWT) technique and analyzed using thematic analysis. RESULTS: Three themes emerged (1) "Security," (2) "My pain" with subthemes: "The pain feelings" and "My sad/happy feelings," (3) "Comfort and relief" with subthemes: "Taking my mind off it," "Resting" and "Hospital things." When in pain children needed to feel secure. Parents and nurses were important in fostering a secure environment for children. Children were capable of describing their pain and identified nonpharmacological strategies to help their pain. PRACTICE IMPLICATIONS: Children as young as 4 years old can provide detailed accounts of their pain, which extends beyond physical dimensions to include visual, auditory, and sensory features. Nurses need to listen, be honest, and develop trust with children to be helpful. Nonpharmacological pain-relieving strategies can be implemented by parents and nurses in collaboration with the child. Fostering a secure environment is essential. PMID- 29790269 TI - Thermally Activated Self-metalation of Carboxy-functionalized Porphyrin Films on MgO Nanocubes. AB - We investigated the adsorption of different free-base carboxyl-functionalized porphyrins, 5,10,15,20-tetrakis(4-carboxyphenyl)-21,23H-porphyrin (2H-TCPP) and 5(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-MCTPP), on MgO nanocubes combining IR, UV/Vis and photoluminescence emission spectroscopy. The thermal behavior of the films was monitored in-situ during annealing. Both porphyrins bind to the nanocubes via one and two acid groups respectively, yielding monolayer films consisting of tilted molecules. For 2H-TCPP, two acid groups remain free and give rise to a characteristic IR band. Self-assembly in a tilted adsorbate layer suppresses metalation at room temperature, in contrast to non-functionalized 2H-TPP, which adsorbs flat-lying. Upon heating, 2H-MCTPP undergoes full metalation at temperatures below 280 degrees C, whereas 2H-TCPP does not metalate at all. The hindered metalation reaction is attributed to the rigidity of the adsorbate film preventing complexation. Our results show that the properties of porphyrin films on oxides can be tuned in a wide range via the position and arrangement of carboxyl anchoring groups. PMID- 29790270 TI - Metabolomics reveals the key role of oxygen metabolism in heat susceptibility of an alpine-dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae). AB - Ghost moths inhabiting the alpine meadows of the Tibetan Plateau are cold-adapted stenothermal organisms that are susceptible to heat (dead within 7 days at 27 degrees C exposure). Exploring the metabolic basis of their heat susceptibility would extend our understanding of the thermal biology of alpine-dwelling invertebrates. Here, gas chromatography-mass spectrometry-based metabolomics was combined with physiological and transcriptional approaches to determine the metabolic mechanisms of heat susceptibility in Thitarodes xiaojinensis larvae. The metabolomics results showed that 27 degrees C heat stress impaired the Krebs cycle and lipolysis in T. xiaojinensis larvae, as demonstrated by the accumulation of intermediary metabolites. In addition, carbohydrate reserves were highly and exclusively consumed, and an anaerobic product, lactate, accumulated. This evidence suggested a strong reliance on glycolysis to anaerobically generate energy. The respiration rate and enzymatic activity test results indicated a deficiency in O2 metabolism; in addition, the Krebs cycle capacity was not decreased, and the metabolic flux through aerobic pathways was limited. These findings were further supported by the occurrence of hypoxia symptoms in midgut mitochondria (vacuolation and swelling) and increased transcription of hypoxia induced factor 1-alpha. Overall, heat stress caused O2 limitation and depressed the overall intensity of aerobic metabolism in ghost moths, and less efficient anaerobic glycolysis was activated to sustain their energy supply. As carbohydrates were depleted, the energy supply became deficient. Our study presents a comprehensive metabolic explanation for the heat susceptibility of ghost moths and reveals the relationship between O2 metabolism and heat susceptibility in these larvae. PMID- 29790271 TI - Correlation between neonatal outcomes of twins depends on the outcome: secondary analysis of twelve randomised controlled trials. AB - OBJECTIVE: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies. DESIGN: Secondary analysis of data from 12 RCTs. SETTING: Obstetric care in multiple countries, 2004-2012. POPULATION OR SAMPLE: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy. METHODS: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models. MAIN OUTCOME MEASURES: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome. RESULTS: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies. CONCLUSIONS: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs. TWEETABLE ABSTRACT: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected. PMID- 29790272 TI - Observation of a Metastable P-Heterocyclic Radical by Muonium Addition to a 1,3 Diphosphacyclobutane-2,4-diyl. AB - A 1,3-diphosphacyclobutane-2,4-diyl contains a unique unsaturated cyclic unit, and the presence of radical-type centers have been expected as a source of functionality. This study demonstrates that the P-heterocyclic singlet biradical captures muonium (Mu=[MU+ e- ]), the light isotope of a hydrogen radical, to generate an observable P-heterocyclic paramagnetic species. Investigation of a powder sample of 2,4-bis(2,4,6-tri-t-butylphenyl)-1-t-butyl-3-benzyl-1,3 diphosphacyclobutane-2,4-diyl using muon (avoided) level-crossing resonance (MULCR) spectroscopy revealed that muonium adds to the cyclic P2 C2 unit. The muon hyperfine coupling constant (AMU ) indicated that the phosphorus atom bearing the t-butyl group trapped muonium to provide a metastable P-heterocyclic radical involving the ylidic MuP(<)=C moiety. The observed regioselective muonium addition correlates the canonical formula of 1,3-diphosphacyclobutane-2,4-diyl. PMID- 29790273 TI - Serological, cultural and molecular evidence of Brucella melitensis infection in goats in Al Jabal Al Akhdar, Sultanate of Oman. AB - Brucellosis, one of the most common zoonotic diseases and has significant public health and economic importance worldwide. Few studies and reports have been performed to estimate the true prevalence of animal brucellosis in the Sultanate of Oman; however, no incidence of the disease was previously reported in Al Jabal Al Akhdar. The purpose of this study was to investigate the prevalence of brucellosis in goats in eight villages in Al Jebal Al Akhdar, Sultanate of Oman, namely: Al Aqaieb, Al Helailat, Al Ghilayil, Hail Al Hedap, Da'an Al Hamra, Shnoot, Al Qasha'e and Al Sarah, Al Jabal Al Akhdar in the Sultanate of Oman. In this study we used different diagnostic serological tests, namely, RBT, I-ELISA and CFT to study the prevalence of Brucella infection in goats in Al Jabal Al Akhdar. Statistical analysis using Kappa statistics was used to compare the performance of the serological tests. Biochemical tests and species-specific Multiplex PCR were used to identify the brucella species involved in the infection. A structured questionnaire and Chi-square (x2 ) statistical analysis was used to identify related brucellosis risk factors. This study is the first to reveal brucellosis infection in goats in eight villages in Al Jebal Al Akhdar, Sultanate of Oman, namely: Al Aqaieb, Al Helailat, Al Ghilayil, Hail Al Hedap, Da'an Al Hamra, Shnoot, Al Qasha'e and Al Sarah, with an overall seroprevalence of 11.1%. The study also compared the performance of three different serological tests, namely, RBT, I-ELISA and CFT. Statistical analysis using Kappa statistics showed that the degree of agreement was best seen between RBT and CFT (96%), followed by RBT, I- ELISA (91.4%) and CFT and I- ELISA (89.2%). Biochemical tests and species-specific Multiplex PCR showed the typical profile for B. melitensis. A structured questionnaire and Chi-square (x2 ) statistical analysis indicated that the presence of abortion is the major risk factor for the prevalence of brucellosis, whereas age and sex were not significant factors in the tested animals. Besides, poor knowledge about brucellosis, consumption of unpasteurized milk or milk products, free trade of animals and the introduction of new animal breeds to herds were all contributing risk factors to the prevalence of brucellosis. The prevalence of human brucellosis obtained verbally from pastoralists gave an insight that brucellosis could pose a public health hazard, especially in those high-risk groups, mainly the pastoralists in the study area. Because of their constant and increasing interaction with their animals, pastoralists could be at a high risk of occupational infection. PMID- 29790274 TI - Polymer scaffolds for pancreatic islet transplantation - Progress and challenges. AB - Pancreatic-islet transplantation is a safe and noninvasive therapy for type 1 diabetes. However, the currently applied site for transplantation, ie, the liver, is not the optimal site for islet survival. Because the human body has shortcomings in providing an optimal site, artificial transplantation sites have been proposed. Such an artificial site could consist of a polymeric scaffold that mimics the pancreatic microenvironment and supports islet function. Recently, remarkable progress has been made in the technology of engineering scaffolds. The polymer-islet interactions, the site of implantation, and scaffold prevascularization are critical factors for success or failure of the scaffolds. This article critically reviews these factors while also discussing translation of experimental studies to human application as well as the steps required to create a clinically applicable prevascularized, retrievable scaffold for implantation of insulin-producing cells for treatment of type 1 diabetes mellitus. PMID- 29790275 TI - Suppressor of clathrin deficiency (Scd6)-An emerging RGG-motif translation repressor. AB - Translation control plays a key role in variety of cellular processes. Translation initiation factors augment translation, whereas translation repressor proteins inhibit translation. Different repressors act by distinct mechanisms to accomplish the repression process. Although messenger RNAs (mRNAs) can be repressed at various steps of translation, most repressors have been reported to target the initiation step. We focus on one such translation repressor, an Arginine-Glycine-Glycine (RGG)-motif containing protein Scd6. Using this protein as a model, we present a discourse on the known and possible functions of this repressor, its mechanism of action and its recently reported regulation. We suggest a case for conservation of the mechanism employed by Scd6 along with its regulation in orthologs, and propose that Scd6 family of proteins will be an ideal tool to understand translation control and mRNA fate decision mechanisms across biological systems. This article is categorized under: Translation > Translation Regulation RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes. PMID- 29790277 TI - First identification of the MHC-DPB2 alleles in the rhesus macaques (Macaca mulatta). AB - We report here the identification of three MHC-DPB2 alleles in the rhesus macaques (Macaca mulatta). PMID- 29790276 TI - Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease. AB - Ustekinumab is applied to induce clinical remission in patients with Crohn's disease. Granulocyte and monocyte absorptive apheresis depletes activated myeloid lineage leukocytes and has been applied for active Crohn's disease. This study retrospectively examined the efficacy and safety of combining intensive granulocyte and monocyte absorptive apheresis and ustekinumab for remission induction therapy in refractory Crohn's disease. Between June and September 2017, three consecutive cases (two females) with refractory Crohn's disease were treated with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab. Crohn's disease activity index, and simple endoscopic score for Crohn's disease at baseline and 10 weeks were applied as treatment efficacy outcomes. In all three cases, at week 10, clinical remission was achieved, while simple endoscopic score for Crohn's disease reflected no improvement. Thus, combination therapy with intensive granulocyte and monocyte absorptive apheresis plus ustekinumab appeared to represent a safe and effective intervention for inducing clinical remission. PMID- 29790278 TI - Split-dose 4-L polyethylene glycol regimen for patients with previous colorectal surgery in bowel preparation before colonoscopy: A randomized, controlled, single blind study. AB - OBJECTIVE: We aimed to investigate the efficacy of a split-dose 4-L polyethylene glycol (PEG) regimen for the quality of bowel preparation in Asian patients with previous colorectal surgery for colorectal cancer (CRC). METHODS: This was a prospective, single-center, randomized controlled, endoscopist-blinded study. Patients with previous colorectal surgery for CRC were randomly allocated to a routine, morning-only 2-L PEG (2-MO) group or a split-dose 4-L PEG (4-SD) group. The primary outcome was a successful bowel preparation rate. Secondary outcomes were polyp detection rate (PDR), adenoma detection rate (ADR), patient compliance, satisfaction, tolerance, willingness to repeat the preparation and difficulty of the bowel preparation process. RESULTS: In total, 187 patients were included (93 in the 2-MO group, 94 in the 4-SD group) in this study. The rate of successful bowel preparation in the 4-SD group was higher than in the 2-MO group (89.4% vs 66.7%, P < 0.001) in an intention-to-treat analysis according to the Aronchick score. Patients' satisfaction with the bowel preparation process in the 4-SD group was superior to that in the 2-MO group (93.4% vs 82.2%, P = 0.021). No significant differences were detected in PDR, ADR, patient compliance, tolerance, willingness to repeat the preparation or difficulty of the bowel preparation process. CONCLUSIONS: The 4-SD PEG regimen was superior to a routine, morning only 2-L PEG preparation for bowel preparation in an Asian population with previous colorectal surgery. PMID- 29790279 TI - The novel HLA-A*02:625 allele was identified in a Chinese bone marrow donor. AB - HLA-A*02:625 differs from HLA-A*02:06:01:01 by a single nucleotide substitution at position 806 C>T. PMID- 29790280 TI - Cas9 versus Cas12a/Cpf1: Structure-function comparisons and implications for genome editing. AB - Cas9 and Cas12a are multidomain CRISPR-associated nucleases that can be programmed with a guide RNA to bind and cleave complementary DNA targets. The guide RNA sequence can be varied, making these effector enzymes versatile tools for genome editing and gene regulation applications. While Cas9 is currently the best-characterized and most widely used nuclease for such purposes, Cas12a (previously named Cpf1) has recently emerged as an alternative for Cas9. Cas9 and Cas12a have distinct evolutionary origins and exhibit different structural architectures, resulting in distinct molecular mechanisms. Here we compare the structural and mechanistic features that distinguish Cas9 and Cas12a, and describe how these features modulate their activity. We discuss implications for genome editing, and how they may influence the choice of Cas9 or Cas12a for specific applications. Finally, we review recent studies in which Cas12a has been utilized as a genome editing tool. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA Protein Complexes. PMID- 29790281 TI - Suppressing tawny crazy ant (Nylanderia fulva) by RNAi technology. AB - The tawny crazy ant (Nylanderia fulva) is a new invasive pest in the United States. At present, its management mainly relies on the use of synthetic insecticides, which are generally ineffective at producing lasting control of the pest, necessitating alternative environmentally friendly measures. In this study, we evaluated the feasibility of gene silencing to control this ant species. Six housekeeping genes encoding actin (NfActin), coatomer subunit beta (NfCOPbeta), arginine kinase (NfArgK), and V-type proton ATPase subunits A (NfvATPaseA), B (NfvATPaseB) and E (NfvATPaseE) were cloned. Phylogenetic analysis revealed high sequence similarity to homologs from other ant species, particularly the Florida carpenter ant (Camponotus floridanus). To silence these genes, vector L4440 was used to generate six specific RNAi constructs for bacterial expression. Heat inactivated, dsRNA-expressing Escherichia coli were incorporated into artificial diet. Worker ants exhibited reduced endogenous gene expression after feeding on such diet for 9 d. However, only ingestion of dsRNAs of NfCOPbeta (a gene involved in protein trafficking) and NfArgK (a cellular energy reserve regulatory gene in invertebrates) caused modest but significantly higher ant mortality than the control. These results suggest that bacterially expressed dsRNA can be orally delivered to ant cells as a mean to target its vulnerabilities. Improved efficacy is necessary for the RNAi-based approach to be useful in tawny crazy ant management. PMID- 29790282 TI - Flexible TiO2 /SiO2 /C Film Anodes for Lithium-Ion Batteries. AB - Flexible TiO2 /SiO2 /C films are prepared by using an electrospinning approach and used as self-supporting electrodes for lithium-ion batteries (LIBs), which exhibit excellent high-rate capability with a capacity of 115.5 mAh g-1 at 8 A g 1 (9.8 C rate) and good storage performance. The LIBs also show high long-term cycling stability of 700 cycles at 200 mA g-1 with a capacity of 380.1 mAh g-1 and a high capacity retention of 88.3 %. Thus, the TiO2 /SiO2 /C films have the potential to serve as electrodes for flexible LIBs, owing to their flexibility and excellent electrochemical performance. PMID- 29790283 TI - Evaluating the predicted extinction risk of living amphibian species with the fossil record. AB - Bridging the gap between the fossil record and conservation biology has recently become of great interest. The enormous number of documented extinctions across different taxa can provide insights into the extinction risk of living species. However, few studies have explored this connection. We used generalised boosted modelling to analyse the impact of several traits that are assumed to influence extinction risk on the stratigraphic duration of amphibian species in the fossil record. We used this fossil-calibrated model to predict the extinction risk for living species. We observed a high consensus between our predicted species durations and the current IUCN Red List status of living amphibian species. We also found that today's Data Deficient species are mainly predicted to experience short durations, hinting at their likely high threat status. Our study suggests that the fossil record can be a suitable tool for the evaluation of current taxa specific Red Listing status. PMID- 29790284 TI - A novel HLA-A*24 allele, A*24:231, was identified by sequence-based typing. AB - HLA-A*24:231 has one nucleotide change from HLA-A*24:02:01:01 at position 784 G>C. PMID- 29790285 TI - Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker. AB - IMPORTANCE: The contribution of the microvascular supply to the pathogenesis of Leber's hereditary optic neuropathy (LHON) is poorly understood. BACKGROUND: We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. DESIGN: Prospective, cross-sectional, multicenter, observational study. PARTICIPANTS: Twenty-two LHON patients divided in four groups: unaffected mutation carriers (LHON-u); early sub-acute stage (LHON-e); late sub-acute stage (LHON-l); chronic stage (LHON-ch). METHODS: OCT-A scans centred on the optic disc were obtained by spectral domain OCT system. MAIN OUTCOME MEASURES: VD, retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were compared between groups. RESULTS: Significant VD changes were detected in every sector (P < 0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. CONCLUSIONS AND RELEVANCE: Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibres revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology. PMID- 29790286 TI - Vascular reconstruction technique of a perforated portal vein during a pediatric total pancreatectomy and islet autotransplant. AB - Hereditary pancreatitis (HP) is a progressive disease that can manifest in childhood with debilitating, relapsing pain. A total pancreatectomy and islet autotransplant (TPIAT) is a surgical option to relieve chronic pain while preserving the available beta-cell mass. The clinical course of HP is fraught with pancreatitis-related sequelae that can both necessitate and complicate a TPIAT. We describe a child with HP who developed a pancreatic pseudocyst-portal vein (PV) fistula. Active hemorrhage of the perforated PV into the pseudocyst and PV thrombosis complicated the planned TPIAT procedure and, preoperatively, required urgent image-guided stenting. During the TPIAT procedure, the endovascular stent was found to be protruding through the PV into the pseudocyst. Using the autologous splenic vein from the TPIAT specimen, we performed a vascular reconstruction of the perforated PV. This case underscores the need for evaluation of children with HP by a multidisciplinary pancreatic TPIAT care team to best prepare for the potential ramifications of pancreatitis-related complications. It also illustrates a useful vascular reconstruction technique for PV complications. PMID- 29790287 TI - Synthesis, Biological Activity, and Mechanism of Action of 2-Pyrazyl and Pyridylhydrazone Derivatives, New Classes of Antileishmanial Agents. AB - In this work, we report the antileishmanial activity of 23 compounds based on 2 pyrazyl and 2-pyridylhydrazone derivatives. The compounds were tested against the promastigotes of Leishmania amazonensis and L. braziliensis, murine macrophages, and intracellular L. amazonensis amastigotes. The most potent antileishmanial compound was selected for investigation into its mechanism of action. Among the evaluated compounds, five derivatives [(E)-3-((2-(pyridin-2 yl)hydrazono)methyl)benzene-1,2-diol (2 b), (E)-4-((2-(pyridin-2 yl)hydrazono)methyl)benzene-1,3-diol (2 c), (E)-4-nitro-2-((2-(pyrazin-2 yl)hydrazono)methyl)phenol (2 s), (E)-2-(2-(pyridin-2 ylmethylene)hydrazinyl)pyrazine (2 u), and (E)-2-(2-((5-nitrofuran-2 yl)methylene)hydrazinyl)pyrazine (2 v)] exhibited significant activity against L. amazonensis amastigote forms, with IC50 values below 20 MUm. The majority of the compounds did not show any toxic effect on murine macrophages. Preliminary studies on the mode of action of members of this hydrazine-derived series indicate that the accumulation of reactive oxygen species (ROS) and disruption of parasite mitochondrial function are important for the pharmacological effect on L. amazonensis promastigotes. PMID- 29790288 TI - National Kidney Foundation Spring Clinical Meetings 2018. AB - Ann M. Carracher, Payal H. Marathe, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Carracher, Marathe, and Close review the latest developments relevant to researchers and clinicians. PMID- 29790289 TI - Catalytic Space Engineering of Porphyrin Metal-Organic Frameworks for Combined CO2 Capture and Conversion at a Low Concentration. AB - Porous porphyrin metal-organic frameworks (PMOFs) provide promising platforms for studying CO2 capture and conversion (C3) owing to their versatility in photoelectric, catalytic, and redox activities and porphyrin coordination chemistry. Herein, we report the C3 application of two PMOFs by engineering the coordination space through the introduction of two catalytic metalloporphyrins doped with rhodium or iridium, Rh-PMOF-1 and Ir-PMOF-1, both of which can serve as heterogeneous catalysts for the chemical fixation of CO2 into cyclic carbonates with yields of up to 99 %. Remarkably, the catalytic reactions can effectively proceed under low CO2 concentrations and high yields of 83 % and 73 % can be obtained under 5 % CO2 in the presence of Rh-PMOF-1 and Ir-PMOF-1, respectively. The synergistic effect of the metalloporphyrin ligand and the Zr6 O8 cluster, in combination with the CO2 concentration effect from the pore space, might account for the excellent catalytic performance of Rh-PMOF-1 under low CO2 concentration. Recycling tests of Rh-PMOF-1 show negligible loss of catalytic activity after 10 runs. PMID- 29790290 TI - Tacrolimus prevents von Willebrand factor secretion by allostimulated human glomerular endothelium. AB - Little is known about the endothelial injury caused directly by circulating donor specific antibodies (DSAs) during antibody-mediated rejection. von Willebrand factor (vWF) is a highly thrombotic glycoprotein stored in Weibel-Palade bodies in endothelial cells. It has been shown that its secretion is triggered by allostimulation. Calcineurin-like phosphatases regulate pathways involved in vWF secretion. Therefore, we hypothesized that tacrolimus would prevent alloantibody induced glomerular lesions, in part via inhibition of vWF secretion from endothelial cells. Here, we used a human in vitro model of glomerular endothelium expressing HLA class I and II antigens and demonstrated that anti-HLA class II antibodies elicit a higher endothelial release of vWF than do anti-HLA class I antibodies in cell supernatants. We observed that tacrolimus treatment decreased vWF secretion after stimulation with both classes of anti-HLA antibodies and decreased platelet adhesion on allostimulated endothelial cells in a microfluidic chamber. In kidney recipients, tacrolimus trough levels were negatively associated with vWF blood levels. These results indicate that direct disruption of hemostasis via vWF secretion is a potential mechanism of antibody-mediated injury in patients with DSAs. Our results further suggest that the targeting of microcirculation hemostasis may be beneficial to prevent the development of microangiopathic lesions in antibody-mediated rejection. PMID- 29790292 TI - Failure of voriconazole therapy due to acquired azole resistance in Aspergillus fumigatus in a kidney transplant recipient with chronic necrotizing aspergillosis. AB - Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole-resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months. PMID- 29790291 TI - The Eyes Have it: A Rheumatologist's View of Uveitis. AB - Uveitis is defined as intraocular inflammation. It is an extraarticular manifestation of many forms of joint disease, which include spondyloarthritis, juvenile idiopathic arthritis, and Behcet's disease. Rheumatologists may be asked to consult on the ophthalmologic care of patients with uveitis in order to identify an associated systemic illness. Diagnoses such as spondyloarthritis, sarcoidosis, and interstitial nephritis with uveitis are frequently overlooked by referring ophthalmologists. Alternatively, rheumatologists may be asked to help manage the patient's immunosuppression, including biologic therapy, which can be required to treat a subset of patients with uveitis. This review is intended to provide rheumatologists with the necessary information to facilitate collaboration in the comanagement of patients with uveitis. PMID- 29790293 TI - The Relationship between Self-reported Restless Sleep and Objectively Measured Physical Activity in Adults with Knee Osteoarthritis. AB - OBJECTIVE: Despite many health benefits of physical activity, inactivity is endemic among adults with knee osteoarthritis (KOA). Because sleep quality may be a target to improve physical activity behavior, we investigated the cross sectional relationship between restless sleep and physical activity in participants with or at risk for KOA. METHODS: We analyzed accelerometer-measured physical activity and clinical data from Osteoarthritis Initiative (OAI) participants. We used multiple regression analysis to evaluate physical activity for participants grouped by the reported frequency of restless sleep adjusting for demographic and medical confounders. RESULTS: Of the 1892 OAI participants with complete data, 300 (16%) reported restless sleep 3 or more days in the past week. Participants reporting much (3-4 days/week) and most (5-7 days/week) restless sleep had 11.9% and 23.7% less weekly minutes of moderate-vigorous activity, respectively, compared to participants reporting rare restless sleep (less than 1 day/week) (p for trend 0.021). These differences persisted after accounting for age, gender, race, body mass index, medical comorbidity, KOA severity and pain (p for trend 0.023). Differences related to restless sleep were largely attenuated by the presence of high depressive symptoms and low energy levels. CONCLUSION: Poor sleep quality is associated with less physical activity in persons with or at risk for KOA. Future studies are needed to determine the mechanisms of how poor sleep and physical activity are related, how energy and depression mediate these relationships, and whether interventions that improve sleep quality might result in increased physical activity. This article is protected by copyright. All rights reserved. PMID- 29790294 TI - JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammatory Mediators in Rheumatoid Arthritis. AB - OBJECTIVE: To examine the effects of tofacitinib on metabolic activity, mitochondrial function, and proinflammatory mechanisms in rheumatoid arthritis (RA). METHODS: Ex vivo RA synovial explants and primary RA synovial fibroblasts (RASFs) were cultured with 1 MUM tofacitinib. RASF bioenergetics were assessed using an XF24 analyzer, and key metabolic genes were assessed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Mitochondrial function was assessed using specific cell fluorescent probes and by mitochondrial gene arrays. Mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay, and lipid peroxidation was quantified by enzyme-linked immunosorbent assay (ELISA). The effect of tofacitinib on spontaneous release of proinflammatory mediators from RA whole tissue synovial explants was quantified by ELISAs/MSD multiplex assays, and metabolic markers were quantified by RT-PCR. Finally, RASF invasion, matrix degradation, and synovial outgrowths were assessed by transwell invasion/Matrigel outgrowth assays and ELISA. RESULTS: Tofacitinib significantly decreased mitochondrial membrane potential, mitochondrial mass, and reactive oxygen species production by RASFs and differentially regulated key mitochondrial genes. Tofacitinib significantly increased oxidative phosphorylation, ATP production, and the maximal respiratory capacity and the respiratory reserve in RASFs, an effect paralleled by a decrease in glycolysis and the genes for the key glycolytic enzymes hexokinase 2 (HK2), glycogen synthase kinase 3alpha (GSK-3alpha), lactate dehydrogenase A, and hypoxia inducible factor 1alpha. Tofacitinib inhibited the effect of oncostatin M (OSM) on interleukin-6 (IL-6) and monocyte chemotactic protein 1 and reversed the effects of OSM on RASF cellular metabolism. Using RA whole tissue synovial explants, we found that tofacitinib inhibited the key metabolic genes for glucose transporter 1, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, 3' phosphoinositide-dependent protein kinase 1, HK2, and GSK-3alpha, the proinflammatory mediators IL-6, IL-8, IL-1beta, intercellular adhesion molecule 1, vascular endothelial growth factor, and TIE-2, and RASF outgrowth from synovial explants, RASF invasion, and matrix metalloproteinase 1 activity. CONCLUSION: This study demonstrates that JAK/STAT signaling mediates the complex interplay between inflammation and cellular metabolism in RA pathogenesis. PMID- 29790295 TI - From noise to knowledge: how randomness generates novel phenomena and reveals information. AB - Noise, as the term itself suggests, is most often seen a nuisance to ecological insight, a inconvenient reality that must be acknowledged, a haystack that must be stripped away to reveal the processes of interest underneath. Yet despite this well-earned reputation, noise is often interesting in its own right: noise can induce novel phenomena that could not be understood from some underlying deterministic model alone. Nor is all noise the same, and close examination of differences in frequency, colour or magnitude can reveal insights that would otherwise be inaccessible. Yet with each aspect of stochasticity leading to some new or unexpected behaviour, the time is right to move beyond the familiar refrain of "everything is important" (Bjornstad & Grenfell ). Stochastic phenomena can suggest new ways of inferring process from pattern, and thus spark more dialog between theory and empirical perspectives that best advances the field as a whole. I highlight a few compelling examples, while observing that the study of stochastic phenomena are only beginning to make this translation into empirical inference. There are rich opportunities at this interface in the years ahead. PMID- 29790296 TI - Not Jessner-Kanof But Cutaneous Lymphoid Hyperplasia Induced by Etanercept: Comment on the Clinical Images Report by Abbad et al. PMID- 29790298 TI - Brief Report: Risk of Childhood Rheumatic and Nonrheumatic Autoimmune Diseases in Children Born to Women With Systemic Lupus Erythematosus. AB - OBJECTIVE: Several autoimmune diseases have familial aggregation and, possibly, common genetic predispositions. In a large population-based study, we evaluated whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of rheumatic and nonrheumatic autoimmune diseases versus children born to mothers without SLE. METHODS: Using the Offspring of SLE Mothers Registry, we identified children born live to SLE mothers and their matched controls, and ascertained autoimmune diseases based on >=1 hospitalization or >=2 physician visits with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetric complications, calendar birth year, and sex of child. RESULTS: A total of 509 women with SLE had 719 children, while 5,824 matched controls had 8,493 children. The mean +/- SD follow-up period was 9.1 +/- 5.8 years. Children born to mothers with SLE had a similar frequency of rheumatic autoimmune diagnoses (0.14%; 95% confidence interval [95% CI] 0.01-0.90) versus controls (0.19% [95% CI 0.11-0.32]). There was a trend toward more nonrheumatic autoimmune diseases in SLE offspring (1.11% [95% CI 0.52-2.27]) versus controls (0.48% [95% CI 0.35-0.66]). In multivariate analyses, we did not see a clear increase in rheumatic autoimmune disease (odds ratio [OR] 0.71 [95% CI 0.11 4.82]), but children born to mothers with SLE had a substantially increased risk of nonrheumatic autoimmune disease versus controls (OR 2.30 [95% CI 1.06-5.03]). CONCLUSION: Although the vast majority of offspring have no autoimmune disease, children born to women with SLE may have an increased risk of nonrheumatic autoimmune diseases versus controls. Additional studies assessing offspring through to adulthood would be additionally enlightening. PMID- 29790297 TI - Selected Cardoon (Cynara cardunculus L.) Genotypes Suitable for PDO Cheeses in Mediterranean Regions. AB - Cardoon flower extract is a traditional and exclusive rennet used for some PDO cheeses in several Mediterranean regions, due to its extremely high concentration in cardosins. In this preliminary study, six individual cardoon genotypes (1M - 6M) were selected because they revealed a wide and consistent diversity of total and specific cardosin concentrations in flowers. During three growing seasons, the stability of 12 biochemical characteristics of flower extracts and 26 plant morphological descriptors was confirmed. Surprisingly, the cardosin profiles of each genotype, based on four main groups A0, A1, A and B, were stable during the annual flower harvesting period and over all three years using ion-exchange chromatography and native-PAGE electrophoresis. This knowledge will allow an improvement in the quality and standardization of cardosin profiles from cardoon flowers used for cheese production and other innovative applications. The results obtained are promising for the development of a plant breeding program based on biochemical and morphological characteristics in order to obtain the most adapted plant architecture for combined purposes related to specific cardosins composition, flower and plant biomass production, and ease of harvesting. PMID- 29790299 TI - 4-Oxo-beta-apo-13-carotenone from the Cyanobacterium Anabaena cylindrica PCC 7122. AB - Apocarotenoids are widely distributed among living organisms (bacteria, fungi, algae, plants and even animals) and have been associated with several signaling functions. These compounds are generated by the activity of carotenoid cleavage dioxygenases (CCDs), whose diversity greatly contributes to the large number of apocarotenoids that have been described so far. It is nevertheless expected that a considerable diversity of these molecules is yet to be discovered. In this work, we describe the isolation and structural elucidation of the apocarotenoid 4 oxo-beta-apo-13-carotenone from the cultured freshwater cyanobacterium Anabaena cylindrica PCC 7122, corresponding to the first report of this compound from natural sources. PMID- 29790301 TI - Identification of eight new MHC-DPB1 alleles in the Tibetan macaques (Macaca thibetana). AB - We report here the identification of eight new Math-DPB1 alleles in the Tibetan macaques. PMID- 29790300 TI - Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems. AB - BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. METHODS: We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. RESULTS: The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. CONCLUSIONS: Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia. PMID- 29790302 TI - Bioactive Constituents of Juniperus turbinata Guss. from La Maddalena Archipelago. AB - A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and alpha terpineol, ent-manoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15 formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained only by synthetic route. The phenolic fraction contained biflavonoids: cupressuflavone (9), followed by minor amounts of amentoflavone (10) and hinokiflavone (11). The essential oil and six purified compounds (1 - 4, 8 and 9) were assessed for biological activities, namely antioxidant (assessed by DPPH. , ABTS.+ and FRAP methods) and cytotoxic effects towards selected human tumor cell lines (MDA-MB 231, A375 and HCT116 cells). Compound 3 exhibited higher radical scavenging activity against ABTS.+ radical than the reference Trolox. Noteworthy, compound 8 showed powerful effects towards tumor cell lines, with IC50 values in the range of 0.060 - 0.201 MUm, which make it a promising anticancer drug candidate. PMID- 29790304 TI - Reducing Bacterial Infections and Biofilm Formation Using Nanoparticles and Nanostructured Antibacterial Surfaces. AB - With the rapid spreading of resistance among common bacterial pathogens, bacterial infections, especially antibiotic-resistant bacterial infections, have drawn much attention worldwide. In light of this, nanoparticles, including metal and metal oxide nanoparticles, liposomes, polymersomes, and solid lipid nanoparticles, have been increasingly exploited as both efficient antimicrobials themselves or as delivery platforms to enhance the effectiveness of existing antibiotics. In addition to the emergence of widespread antibiotic resistance, of equal concern are implantable device-associated infections, which result from bacterial adhesion and subsequent biofilm formation at the site of implantation. The ineffectiveness of conventional antibiotics against these biofilms often leads to revision surgery, which is both debilitating to the patient and expensive. Toward this end, micro- and nanotopographies, especially those that resemble natural surfaces, and nonfouling chemistries represent a promising combination for long-term antibacterial activity. Collectively, the use of nanoparticles and nanostructured surfaces to combat bacterial growth and infections is a promising solution to the growing problem of antibiotic resistance and biofilm-related device infections. PMID- 29790303 TI - Association Between Reappearance of Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Subgroup Analysis of Nationwide Prospective Cohort Studies. AB - OBJECTIVE: To evaluate clinical links between levels of myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and relapse in patients with ANCA associated vasculitis (AAV) using a data set from 2 nationwide prospective cohort studies. METHODS: From the cohort studies, MPO-ANCA-positive patients who achieved remission during the 6 months after remission induction therapy were enrolled. We measured MPO-ANCA levels at months 0, 3, 6, 12, 18, 24, and at the time of relapse. The primary outcome measure was relapse. A nested case-control analysis and multivariable analysis were performed to investigate the relationship between ANCA reappearance and relapse. RESULTS: Of 271 patients, 183 were classified as having microscopic polyangiitis, 34 as having granulomatosis with polyangiitis, 15 as having eosinophilic granulomatosis with polyangiitis, and 39 were unclassifiable. The median age was 73 years, and 165 (61%) were female. In 195 patients (72%), MPO-ANCA levels decreased to normal levels within 6 months after commencement of treatment, and MPO-ANCA reappeared in 73 of 181 patients (40%) with complete follow-up data. Reappearance of MPO-ANCA was more frequent in patients with relapse than in 75 age- and sex-matched control patients without relapse (odds ratio 26.2 [95% confidence interval 8.2-101], P < 0.0001) after adjustment for confounding factors. CONCLUSION: Reappearance of MPO ANCA could be a clinically useful biomarker for predicting relapse in patients with MPO-ANCA-positive AAV in remission. This suggests that routine MPO-ANCA monitoring should be implemented in this patient population. PMID- 29790305 TI - Correlation of Lyme Disease-Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic-Refractory Lyme Arthritis. AB - OBJECTIVE: To determine whether IgG subclasses of Borrelia burgdorferi antibodies differ from those of 3 Lyme disease (LD)-associated autoantibodies. METHODS: IgG antibody subclasses were determined by enzyme-linked immunosorbent assay in serum samples from 215 patients with features representative of each of the 3 stages of LD. Antibody and cytokine profiles were measured in matched serum and synovial fluid (SF) samples from patients with Lyme arthritis. Synovial tissue from patients with antibiotic-refractory arthritis was examined for histologic features, IgG subclasses of plasma cells, and messenger RNA (mRNA) subclass expression. RESULTS: B burgdorferi antibodies were primarily of the IgG1 and IgG3 subclasses, and the levels increased as the infection progressed. In contrast, LD associated autoantibodies were mainly of the IgG2 and IgG4 subclasses, and these responses were found primarily in patients with either antibiotic-refractory or antibiotic-responsive arthritis, particularly in SF. However, compared with the responsive group, the inflammatory milieu in SF in the refractory group was enriched for cytokines representative of innate, Th1, Th2, and Th17 responses. Synovial tissue in a subgroup of patients with refractory arthritis showed marked expression of mRNA for IgG4 antibodies and large numbers of IgG4-staining plasma cells. IgG4 autoantibodies in SF to each of the 3 LD-associated autoantigens correlated with the magnitude of obliterative microvascular lesions and fibrosis in the tissue. CONCLUSION: Our findings indicate that the subclasses of IgG antibodies to B burgdorferi differ from those of LD-associated autoantibodies. Furthermore, the correlation of IgG4 autoantibodies with specific synovial pathology in the refractory group suggests a role for these autoantibodies, either protective or pathologic, in antibiotic-refractory Lyme arthritis. PMID- 29790307 TI - Necrotising sialometaplasia: a diagnostic perplexity? An innocent entity to malignant masquerade. AB - objective: Necrotising Sialometaplasia is a benign self limiting reactive condition of major and minor salivary glands, which can arouse suspicion for malignancy, clinically and histopathologically. Here, we report a case of 38-year old female with a painful ulcer on the palate. The case enlightens the importance of clinicopathologic correlation and diligent follow up in diagnosis and management of the case. PMID- 29790306 TI - The role of novel prognostic markers PROX1 and FOXC2 in carcinogenesis of oral squamous cell carcinoma. AB - objective: Oral squamous cell carcinoma is the most common malignant tumor of the head and neck regions and accounts for more than 90% of cancers in the oral cavity. The angiogenesis, lymphangiogenesis and epithelial mesenchymal transition are known to be pivotal for tumor progression and metastasis. In the last decade, much data has been generated concerning the molecular mechanisms of angiogenesis, lymphangiogenesis and its significance in pathological conditions. The main angiogenic and lymphangiogenic factors have been identified as vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR-2), forkhead box (FOX) C2 while vascular endothelial growth factor C/D (VEGF-C/D), vascular endothelial growth factor receptor 3 (VEGFR-3), Prospero homeobox 1 (PROX1), LYVE-1, podoplanin, Tie/Angioprotein (Ang) 2 and EphrinB2 respectively. PROX1 is a mammalian homologue of Drosophilia homeobox protein, prospero and important for the embryonic development of many mammalian tissues. It has been suggested that it plays various tissue dependent functional roles, which reflects both oncogenic potential and a tumor suppressive role. The exact role in OSCC remains controversial. FOXC2 is a transcription factor belongs to large family of protein, forkhead box. It has been shown to be involved in cancer angiogenesis, proliferation and metastasis through its induction of epithelial-to mesenchymal transition while its significance in OSCC remains unknown. Based on these data, this article reviews the role of novel prognostic factors PROX1 and FOXC2 in carcinogenesis of OSCC so that they might be considered as an attractive therapeutic target for both tumor associated blood vessels, lymphatic vessels and tumor cells. PMID- 29790308 TI - Impact of low level radiation on concentrations of some trace elements in radiation workers. AB - Introduction: Small variations in trace element levels may cause important physiological changes in the human body. This study aims to evaluate five important trace elements in radiation workers. Method: In this study, 44 radiation workers and an equal number of non-radiation workers were selected as the case and control group, respectively. The concentrations of iron, magnesium, zinc, copper, and selenium in the serum of the participants were measured using an Atomic Absorption Spectrometry (AAS). Results: The mean concentrations of iron, magnesium, zinc, copper, and selenium for the case group were 107.3 ug/dl, 2.3 mg/dl, 80.9 ug/dl, 112.6 ug/dl and 216.7 ng/ml, respectively. The results for the control group were 121.9 ug/dl, 2.3 mg/dl, 82.3 ug/dl, 112.8 ug/dl and 225.2 ng/ml, respectively. Conclusions: The mean concentration of iron in the case group was significantly lower than the control group (p-value = 0.012), while the concentrations of other elements in both of the groups were not significantly different. In the case group, except magnesium (p-value = 0.021), no significant relationship was found between age and the elemental concentrations. According to Spearman's test, there was a meaningful statistical correlation between the sex and concentration of iron, Mg, Zn, and Se. Also, the correlation between the concentration of magnesium and the weights of radiation workers was significant (p-value =0.044). PMID- 29790309 TI - Assessment of hospital based prevalence of oral cancer among population of Kanpur, Uttar Pradesh. AB - Background: Oral cancer incidence depends on both qualitative and quantitative factors wherein the incidence of oral cancer in patients with smoking and tobacco chewing habit is 8.4 times higher than that of patients with no habit. Aim: To understand about the prevalence of oral cancer in population of Kanpur reported to the hospital and analyse the association with age, gender and tobacco habit. Material and Method: All 320 cases of Squamous cell carcinoma diagnosed histopathologically, since January 2007 to December 2016, were retrieved from the archives and a retrospective study was conducted along with association with the variables such as age, gender, site, habit and histopathological type. Results: A total of 71 cases were reported in the age group of 30-39 (22.18%) and 60 cases (18.75%) were seen to be below 30yrs. Among individuals with habit, 135 (42.18%) were tobacco chewers and smoking was prevalent in about 48 (15%). The prevalence was more in males 37 (15.22%). Amongst both males (44.03%) and females (48.05%) gingivo-buccal sulcus was the most common site. The least common site was seen to be lip with only 10 (3.12%) patients. Well differentiated squamous cell carcinoma was common in both males and females with 155 (63.78%) and 47 (61.03%) respectively. Poorly differentiated squamous cell carcinoma was only reported in 4(1.64%) males. Conclusion: Early detection of these oral cancers will enable appropriate clinical management and monitoring. Moreover, improving the incidence, mortality, and survival rates of oral cancer requires a multi-tier structural approach that targets society, dentists, communities, and the individual. PMID- 29790310 TI - Anticancer activity of chlorhexidine and cranberry extract: an in-vitro study. AB - Introduction: Oral cancer is considered to be a global pandemic. The study was conducted to assess the anti-cancer activities of Chlorhexidine (CHX) and Cranberry against oral cancer cell lines. Material and Methods: Anticancer activity of CHX and Cranberry extract (CE) was assessed against AW13516 (poorly to moderately differentiated squamous cell carcinoma of tongue) and KB (Nasopharyngeal carcinoma) using Sulforhodamine B (SRB) assay at the Advanced Centre for Treatment Research and Education in Cancer (ACTREC) Mumbai, India. Three dose related parameters GI50, TGI and LC50 were calculated for each drug. Results: CE (80ug/ml) showed no anti-cancer property against AW13516 cell line; however it showed 70.6% growth inhibition against KB cell line. CHX demonstrated 80.15% & 95.7% of growth inhibition against AW13516 & KB cell line respectively. Both the drugs were less potential than positive control drug Adriamycin, as reflected by their GI50, TGI and LC50 values. Conclusion: CHX exhibited better anti-cancer properties than CE for both the oral cancer cell lines. PMID- 29790311 TI - Invasive molar pregnancy in rudimentary uterine horn. AB - objective: Incidence of molar pregnancy is 1-3/1000 pregnancies. Invasive mole is a local invasive form of gestational trophoblastic neoplasias which is mostly seen in reproductive age and usually follows a molar pregnancy and rarely has an initial presentation. Ectopic pregnancy in rudimentary uterine horn is extremely rare and is seen in 1/100,000 - 140,000 pregnancies. Invasive mole has seldom been reported in ectopic localizations but not in a patient with Mullerian duct anomaly. Here we represent a case of invasive mole in a reproductive age patient with unicornuate uterus and rudimentary communicating uterine horn. Invasive mole presented initially, mimicking ectopic pregnancy. The patient underwent diagnostic laparoscopy and resection of rudimentary uterine horn was performed. The pathology result was reported as an invasive mole. Serum b-hCG levels normalized on post-operative first month and no additional chemotherapy was needed. PMID- 29790312 TI - Cavitary myiasis and its management. AB - objective: Myiasis is a parasitic disease of humans and vertebrates, caused by fly larvae feeding on the host's necrotic or living tissue. Myiasis is classified into cutaneous and cavitary myiasis. Cavitary myiasis is rare and occurs more frequently in tropical and subtropical regions of Africa and America associated with low economic status and poor hygiene. This article reviews current literature, provides general descriptions, and discusses life cycles of each species. It also gives diagnosis, treatment techniques and descriptions of each type of illness that result from interaction / infestation. PMID- 29790313 TI - Quality of life of cancer patients. AB - objective: Cancer is a one of the major public health problem both in developed and developing countries around the globe. Quality-of-life (QOL) of a cancer patient before and after the treatment is an important issue especially for the cancer survivors, their families, and the care providers. In cancer prospective, Quality-of-life can been defined as a sense of well-being, it is a multidimensional perspective that includes dimensions such as physical, psychological, social, and spiritual, changes in one QOL dimension can influence perceptions in other dimensions also. Cancer patients should demand information related to adverse effects of chemotherapy and actions to be taken to reduce them, also there should be provision of providing sufficient information prior to beginning of the treatment procedure irrespective to type of treatment, so that patient is aware of all the treatment modalities and their side effects and self care strategies so as to reduce treatment-related concerns. PMID- 29790314 TI - Superselective intraarterial cerebral infusion of cetuximab with blood brain barrier disruption combined with Stupp Protocol for newly diagnosed glioblastoma. AB - objective: We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/m2). The second and third SIACI of cetuximab were administered 3 and 6 months later, while the patient continued on maintenance temozolomide. Post-radiation changes on MRI were stable, and there were no signs of recurrence at 4 and 6 months post-resection. Herein, we detail the technical aspects of this novel treatment paradigm and suggest that SIACI of cetuximab after BBB disruption using mannitol, combined with the standard of care chemoradiation therapy, may be an effective treatment method for newly diagnosed EGFR amplified glioblastoma. PMID- 29790315 TI - Inhibitory effects of mushroom extracts on progression of carcinogenesis in mice. AB - objective: Hepatocellular carcinoma is a common primary malignancy of hepatocytes that has caused many fatalities globally. To manage the increasing cases of hepatocellular carcinoma, natural products like mushrooms have been tested for their anti-oxidant, anti-tumour and therapeutic properties. This study aimed to investigate the effect of Agaricus bisporus on progression of chemically induced carcinogenesis in mice. Carcinogenesis was induced in experimental and positive group of mice. Development and progression of carcinogenesis was monitored by quantifying levels of Lactate dehydrogenase, total sialic acid and by histological analysis. The results of the study showed that, unlike lactate dehydrogenase, the levels of sialic acid consistently decreased throughout the experimental period in mice that were fed on mushroom extracts compared to the positive control. Histological analysis also showed protection of the hepatocytes from carcinogenesis progression. Overall, the results from tumour markers and histological analysis, showed that addition of Agaricus bisporus extracts to diet slowed down progression of carcinogenesis and these extracts therefore may be useful as supplementary diet to conventional cancer therapies. PMID- 29790316 TI - Chronic non-healing ulcer of the oral cavity: tuberculosis or carcinoma? AB - objective: Tuberculosis is a chronic granulomatous lesion, which primarily has an affinity for the lungs. It can involve other sites like lymph nodes, kidney, oral cavity. Infection of the oral cavity by M. tuberculosis can be as a Primary infection or as a Secondary infection. Primary presentation of oral tuberculosis is in the form of the chronic non healing ulcer. A Primary infection or an Asymptomatic Secondary infection can impose a great diagnostic dilemma, as it may mimic neoplasia. Here we present a case of a 32-year-old asymptomatic female with secondary infection. PMID- 29790317 TI - Cancer Cell Controller. AB - objective: Cancer is the disease which exists when the cell is uncontrolled. This paper presents a controller for the same. The cancer cell is reviewed via algebraic structures. PMID- 29790318 TI - Cancer medicine: a direction. AB - objective: The medicine of cancer is directed in this paper. The pie theory is applied for the proposed medicine. The improbability and un-constancy are the major theories, which are used to design this anti-cancer medicine. PMID- 29790319 TI - Wideband linear detector arrays for optoacoustic imaging based on polyvinylidene difluoride films. AB - We provide direct experimental comparison of the optoacoustic imaging performance of two different 64-element linear detector array (LDA) units based on polyvinylidene difluoride (PVDF) films. The first LDA unit was based on traditional flexible circuit (FC) technology and consisted of an FC glued to the nonmetalized signal surface of a 28-MUm-thick PVDF film providing 300 / 80-MUm axial resolution/lateral resolution (AR/LR) and 0.4-kPa noise equivalent pressure of its single element. The other LDA unit was manufactured using a technology of low-temperature photolithographic etching (PE) of a signal electrode onto a 25 MUm-thick PVDF film providing 300 / 40-MUm AR/LR and 1 kPa noise equivalent pressure. As compared with a previously reported LDA unit based on a 100-MUm PVDF thick film, the main advantage of using the thinner PVDF films was 10-fold improvement in axial resolution, whereas the main drawback was 10-fold increased noise equivalent pressure. In terms of in vivo imaging performance, higher bandwidth of PE LDA probe was more important than the higher sensitivity of FC LDA unit. PMID- 29790320 TI - Ultrasonic standing wave preparation of a liquid cell for glucose measurements in urine by midinfrared spectroscopy and potential application to smart toilets. AB - Smart toilets could be used to monitor different components of urine in daily life for early detection of lifestyle-related diseases and prompt provision of treatment. For analysis of biological samples such as urine by midinfrared spectroscopy, thin-film samples like liquid cells are needed because of the strong absorption of midinfrared light by water. Conventional liquid cells or fixed cells are prepared based on the liquid membrane method and solution technique, but these are not quantitative and are difficult to set up and clean. We generated an ultrasonic standing wave reflection plane in a sample and produced an ultrasonic liquid cell. In this cell, the thickness of the optical path length was adjustable, as in the conventional method. The reflection plane could be generated at an arbitrary depth and internal reflected light could be detected by changing the frequency of the ultrasonic wave. We could generate refractive index boundaries using the density difference created by the ultrasonic standing wave. Creation of the reflection plane in the sample was confirmed by optical coherence tomography. Using the proposed method and midinfrared spectroscopy, we discriminated between normal urine samples spiked with glucose at different concentrations and obtained a high correlation coefficient. PMID- 29790321 TI - An enquiry into young men at risk of suicide in the UK. AB - Men are at a higher risk of suicide; 70% of people who die by suicide are men. By exploring some of the reasons behind suicide in young men aged 15-29 years old, this article will look at not just the influence of perceived physical strength, but also their mental state of mind. The article combines information from the World Health Organization, research conducted in other countries and the information available in the UK, to hopefully benefit and encourage further research to be carried out. Men's mental health is at the forefront of many campaigns, but there is still a lack of understanding about why suicide occurs. PMID- 29790322 TI - [Editorial.A year full of news for Italian nurses]. PMID- 29790323 TI - [Prevalence and risk factors of overweight and obesity after liver transplantation: retrospective study at three years after transplantation]. AB - BACKGROUND AND AIM: Weight gain is frequently observed among liver transplanted patients. This condition is often associated to the development of other post LT morbidities which might influence the long-term post-transplant survival. However, the risk factors asso- ciated have not yet been identified. The aim of this study was to assess the prevalence of over- weight and obesity, to notice Body Mass Index changes and associated risk factors, within three years after LT. METHODS: All the patients consecutively transplanted at the Liver Transplantation Unit of Fondazione IRCCS "Ca-Granda Ospedale Maggiore Policlinico", Milan between January 2005 and June 2014 were retrospectively evaluated for inclusion. Clinical, Biochemical and pharmaco- logical data were collected at hospital discharge and at 1st,2nd and 3rd years post-LT. RESULTS: 145 patients, 95(66%) male, 53 years (44-59 yr), 48(33%) HBV+HDV positive and 30(21%)alcohol abusers pre LT, were enrolled. At hospital discharge patients' BMI was 21.9 Kg/m2 (IQR: 20.1-24.1 Kg/m2) and the prevalence of overweight was 14%. The same para- meters after 1,2 and 3 years of follow-up were 25.6 Kg/m2 and 40%, 25.5 Kg/m2 and 41%, 25.4 Kg/m2 and 37%. The main weight gain was 9.8 Kg during the 1st year after LT while only 0.9 Kg and 0.5 Kg during the 2nd and 3rd year, respectively, No correlation between weight gain and any clinical, biochemical and pharmacological parameters considered was observed. DISCUSSION: The weight gain and the development of obesity are predominant during the first year after LT; this is probably due to an improper diet and lack of physical activity. PMID- 29790324 TI - [Interruptions during nursing handover: observational study in an italian intensive care unit]. AB - AIM: the purpose of this study is to investigate interruptions as they occur during the nursing handover in an Italian Intensive Care Unit. METHOD: prospective observational study carried out in the Lecco hospital's Department of Anaesthesiology and Critical Care Service (formerly A. Manzoni Hospital) from 15th July 2016 to 30th December 2016. To capture and understand the causes and occurences of interruptions, data were collected through participating observa- tion. RESULTS: the mean handover time was 7.31 (standard deviation [SD] +/-3.27) min with a range of 3-25 min. A total of 422 nursing handovers and 352 interruptions were collected with a mean of interruptions for handover of 0.83 (standard deviation [SD] =+0.66). The first author of the interruptions was detected to be the nursing department staff. The interruptions were observed indepentenly of the place of handover. CONCLUSION: Nurses interrupt and allow themselves to be interrupted by collabora- tors, primarily by their nurse collegues and the frequency of interruptions are particu- rarly worrying. After our results, further studies are needed to gather information and data in setting more heterogeneous. PMID- 29790325 TI - [Pathological gambling and internet addiction among nursing students: a pilot study]. AB - AIM: To assess pathological gambling and Internet addiction among nursing students. METHOD: A monocentric, observational study was carried out from November 2013 to January 2014 at an Italian Nursing Degree Course using the Italian version of the South Oaks Gambling Screen (SOGS) to assess the risk to develop gambling, and the Internet Addiction Test (IAT) to assess the risk to develop Internet addiction. A total of 420 nursing students were enrolled. RESULTS: Two hundred eighty-three students (67.4%) participated; 11.3 % of participants were identified as ''at-risk'' of pathological gambling (SOGS scores of 1 to 4), whereas the 0.7 % of students were identified as probable pathological gamblers (SOGS scores >=5). The prevalence of Internet addiction in the sample was 8.8% (IAT scores >=50). Also, findings showed that students with Internet addiction had a higher risk of developing pathological gambling (B = 0,16; p = 0.005). CONCLUSIONS: The prevalence of pathological gambling and Internet addiction in our sample is relatively small. However, the percentage of students who could be at-risk for gambling and Internet addiction related problems is noteworthy. Further multicenter studies are needed to better understand the association between gambling and Internet addiction among nursing students. PMID- 29790326 TI - [The quality of life as perceived by older people. Results of a phenomenological study]. AB - INTRODUCTION: Elderly Quality of life (QoL) is vulnerable because of the decline in physical and mental capacity, discharge from work, rupture of the family and isolation. Many QoL Scales are made for adults: there is little research investigating how older people perceive QOL. AIM: This study aims to explore and understand the perceptions that older people have about their QOL. METHOD: A qualitative research hermeneutics-phenomenological was done. Narratives were analyzed by mixed method phenomenological-grounded (Mortari, 2007). RESULTS: 16 elderly were interviewed (aged between 80 and 93 years), residents in their home. The analysis of the interviews confirm that QoL is a multidimensional concept that encompasses several components of life. There were 7 shared themes, reflecting the experience of well-being in older people living at home. The dimensions are: living relationships that drive away loneliness, fill the time with activities that follow their own interests, accept themselves as elderly person, choose how and where to live, think about death. CONCLUSIONS: The results of the study show that older people perceive QOL as made of multiple components and variables. Elderly are focused on the remaining capacities, on the acceptance of the positive aspects of their lives rather than on what they can no longer do. This study help to identify some social and health strategies to guarantee the best way to live the last part of life. PMID- 29790327 TI - [The effective educational interventions in the promotion of self-care in people with heart failure: a literature review]. AB - INTRODUCTION: Self-care in people with heart failure is subject of recent middle range and short-range nursing theories and its promotion is recognized as a sensitive nursing outcome, achievable through various strategies including education. PURPOSE: To identify educational interventions that are effective in the promotion of self-care in adults and elderly people with heart failure, evaluating educational methods and tools used and their effectiveness in the medium-long term period. METHOD: We conducted a literature review, beginning with a search of secondary studies consulting Cochrane Library and than searching for the most recent primary studies in these scientific databases: PubMed, CINAHL, Scopus, and PsycINFO. RESULTS: The information meeting, focused on cognitive learning method, is the most frequently used and it shows a good and heterogeneous effectiveness in the promotion of self- care. The best statically significant results were obtained from the integration of this method with patients' training and counseling, relating respectively to the psycho-motor and psycho- affective learning. In support of the hetero-directed interventions were useful informational tools, self-monitoring tools and facilitating tools. The education was effective in promoting self-care until 12 months in most of the studies. CONCLUSIONS: The selected literature shows that is difficult to identify the best method or educational tool and that a single intervention is often not enough to promote self-care. Heal- thcare providers need to think about education as a continuous and dynamic process that includes multiple sessions and encourages the participation of the patient, turning the meeting into a discussion time where any provided is useful to answer to specific situations through activities and relationships. PMID- 29790328 TI - Patients and caregivers' knowledge of chronic obstructive pulmonary disease. AB - BACKGROUND: Knowledge of chronic obstructive pulmonary disease (COPD) is important for the disease self-management. AIM: This study aimed to assess the level of knowledge in Italian patients with COPD and their caregivers and to determine factors influencing their knowledge. METHODS: We used a descriptive correlational design. Knowledge was assessed with the Bristol COPD knowledge questionnaire (BCKQ) that was translated in Italian through the forward-backward translation method. BCKQ was administered to a convenience sample of 142 patients with COPD and 51 caregivers. RESULTS: The mean age for patients and caregivers was respectively 77 years (range 45-93) and 62 years (range 28-85). Patients were mostly men, had a low education level and 30% had severe or very severe COPD, while caregivers were mostly female and with higher education level. The patients answered correctly to 48% of the BCKQ whereas caregivers to 59%. In patient caregiver dyads, a good level of agreement on the knowledge was found in 35 items out of 65. In patients, the knowledge was not correlated with age, gender, education, years or severity of disease whereas in caregivers it was fairly correlated with the education level. CONCLUSIONS: Our study showed that patients and caregivers possess limited knowledge of COPD, especially on chest infections, and exacerbations. Factors that limit or promote the acquisition of knowledge in people with COPD and their caregivers should be investigated. PMID- 29790329 TI - Controllable Synthesis of Multiheteroatoms Co-Doped Hierarchical Porous Carbon Spheres as an Ideal Catalysis Platform. AB - The synthesis of porous carbon spheres with hierarchical porous structures coupled with the doping of heteroatoms is particularly important for advanced applications. In this research, a new route for efficient and controllable synthesis of hierarchical porous carbon spheres co-doped with nitrogen, phosphorus, and sulfur (denoted as NPS-HPCs) was reported. This new approach combines in situ polymerization of hexachlorocyclophosphazene and 4,4' sulfonyldiphenol with the self-assembly of colloidal silica nanoparticles (SiO2 NPs). After pyrolysis and subsequent removal of the SiO2 NPs, the resulting NPS HPCs possess a high surface area (960 m2/g) as well as homogeneously distributed N, P, and S heteroatoms. The NPS-HPCs are shown to be an ideal support for anchoring highly dispersed and uniformly sized noble metal NPs for heterogeneous catalysis. As a proof of concept, Pd NPs are loaded onto the NPS-HPCs using only methanol as a reductant at room temperature. The prepared Pd/NPS-HPCs are shown to exhibit high activity, excellent stability, and recyclability for hydrogenation of nitroarenes. PMID- 29790330 TI - Sub-Parts-per-Million Hydrogen Sulfide Colorimetric Sensor: Lead Acetate Anchored Nanofibers toward Halitosis Diagnosis. AB - Lead(II) acetate [Pb(Ac)2] reacts with hydrogen sulfide to form colored brownish precipitates of lead sulfide. Thus far, in order to detect leakage of H2S gas in industrial sectors, Pb(Ac)2 has been used as an indicator in the form of test papers with a detection limit only as low as 5 ppm. Diagnosis of halitosis by exhaled breath needs sensors able to detect down to 1 ppm of H2S gas. In this work, high surface area and porous Pb(Ac)2 anchored nanofibers (NFs) that overcome limitations of the conventional Pb(Ac)2-based H2S sensor are successfully achieved. First, lead(II) acetate, which melts at 75 degrees C, and polyacrylonitrile (PAN) polymer are mixed and stirred in dimethylformamide (DMF) solvent at 85 degrees C, enabling uniform dispersion of fine liquid droplets in the electrospinning solution. During the subsequent electrospinning, Pb(Ac)2 anchored NFs are obtained, providing an ideal nanostructure with high thermal stability against particle aggregation, numerous reactions sites, and enhanced diffusion of H2S into the three-dimensional (3D)-networked NF web. This newly obtained sensing material can detect down to 400 ppb of H2S at a relative humidity of 90%, exhibiting high potential feasibility as a high-performance colorimetric sensor platform for diagnosis of halitosis. PMID- 29790331 TI - Development of an Electrochemical Paper-Based Analytical Device for Trace Detection of Virus Particles. AB - Viral pathogens are a serious health threat around the world, particularly in resource limited settings, where current sensing approaches are often insufficient and slow, compounding the spread and burden of these pathogens. Here, we describe a label-free, point-of-care approach toward detection of virus particles, based on a microfluidic paper-based analytical device with integrated microwire Au electrodes. The device is initially characterized through capturing of streptavidin modified nanoparticles by biotin-modified microwires. An order of magnitude improvement in detection limits is achieved through use of a microfluidic device over a classical static paper-based device, due to enhanced mass transport and capturing of particles on the modified electrodes. Electrochemical impedance spectroscopy detection of West Nile virus particles was carried out using antibody functionalized Au microwires, achieving a detection limit of 10.2 particles in 50 MUL of cell culture media. No increase in signal is found on addition of an excess of a nonspecific target (Sindbis). This detection motif is significantly cheaper (~$1 per test) and faster (~30 min) than current methods, while achieving the desired selectivity and sensitivity. This sensing motif represents a general platform for trace detection of a wide range of biological pathogens. PMID- 29790332 TI - Atomic Layer Epitaxy of Aluminum Nitride: Unraveling the Connection between Hydrogen Plasma and Carbon Contamination. AB - Atomistic control over the growth of semiconductor thin films, such as aluminum nitride, is a long-sought goal in materials physics. One promising approach is plasma-assisted atomic layer epitaxy, in which separate reactant precursors are employed to grow the cation and anion layers in alternating deposition steps. The use of a plasma during the growth-most often a hydrogen plasma-is now routine and generally considered critical, but the precise role of the plasma is not well understood. We propose a theoretical atomistic model and elucidate its consequences using analytical rate equations, density functional theory, and kinetic Monte Carlo statistical simulations. We show that using a plasma has two important consequences, one beneficial and one detrimental. The plasma produces atomic hydrogen in the gas phase, which is important for removing methyl radicals left over from the aluminum precursor molecules. However, atomic hydrogen also leads to atomic carbon on the surface and, moreover, opens a channel for trapping these carbon atoms as impurities in the subsurface region, where they remain as unwanted contaminants. Understanding this dual role leads us to propose a solution for the carbon contamination problem which leaves the main benefit of the plasma largely unaffected. PMID- 29790333 TI - Autonomous Scanning Probe Microscopy in Situ Tip Conditioning through Machine Learning. AB - Atomic-scale characterization and manipulation with scanning probe microscopy rely upon the use of an atomically sharp probe. Here we present automated methods based on machine learning to automatically detect and recondition the quality of the probe of a scanning tunneling microscope. As a model system, we employ these techniques on the technologically relevant hydrogen-terminated silicon surface, training the network to recognize abnormalities in the appearance of surface dangling bonds. Of the machine learning methods tested, a convolutional neural network yielded the greatest accuracy, achieving a positive identification of degraded tips in 97% of the test cases. By using multiple points of comparison and majority voting, the accuracy of the method is improved beyond 99%. PMID- 29790334 TI - Correction to "Mechanism of the Ferrocyanide-Iodate-Sulfite Oscillatory Chemical Reaction". PMID- 29790335 TI - Accurate Electron-Nucleus Distances from Paramagnetic Relaxation Enhancements. AB - Measurements of paramagnetic relaxation enhancements (PREs) in 1H NMR spectra are an important tool to obtain long-range distance information in proteins, but quantitative interpretation is easily compromised by nonspecific intermolecular PREs. Here we show that PREs generated by lanthanides with anisotropic magnetic susceptibilities offer a route to accurate calibration-free distance measurements. As these lanthanides change 1H chemical shifts due to pseudocontact shifts, the relaxation rates in the paramagnetic and diamagnetic state can be measured with a single sample that simultaneously contains the protein labeled with a paramagnetic and a diamagnetic lanthanide ion. Nonspecific intermolecular PREs are thus automatically subtracted when calculating the PREs as the difference in nuclear relaxation rates between paramagnetic and diamagnetic protein. Although PREs from lanthanides with anisotropic magnetic susceptibilities are complicated by additional cross-correlation effects and residual dipolar couplings (RDCs) in the paramagnetic state, these effects can be controlled by the choice of lanthanide ion and experimental conditions. Using calbindin D9k with erbium, we succeeded in measuring intramolecular PREs with unprecedented accuracy, resulting in distance predictions with a root-mean-square deviation of <0.9 A in the range 11-24 A. PMID- 29790336 TI - Importance of Dermal Absorption of Polycyclic Aromatic Hydrocarbons Derived from Barbecue Fumes. AB - Despite the ubiquity and carcinogenicity of polycyclic aromatic hydrocarbons (PAHs), their dermal absorption for the general population has not been adequately addressed. Aiming to verify the importance of dermal absorption of PAHs, barbecue (BBQ) in Guangzhou, China was chosen as a case study. Urine samples were collected and analyzed for nine hydroxyl (OH)-PAHs. Air, food, and cotton clothing samples were analyzed for 16 PAHs. Dietary exposure was the dominant exposure route with the greatest amounts of OH-PAH excretion and PAH intake. Dermal intake of low molecular-weight PAHs was greater than inhalation intake from the occurrence of atmospheric PAHs. In addition, the net excreted amounts of OH-naphthalene, OH-fluorene, OH-phenanthrene, and OH-pyrene via dermal absorption were 367, 63, 98, and 28 ng, respectively, upon 2.5-h exposure, comparable to those via combined dermal and inhalation exposure, which were 453, 98, 126, and 38 ng. The ratios of excretion to intake via dermal absorption were 0.11, 0.036, and 0.043 for fluorene, phenanthrene, and pyrene, respectively, lower than the ratios from dietary exposure (0.38, 0.14, and 0.060) but higher than the ratios from inhalation (0.097, 0.016, and 0.025). In the case of BBQ fumes, dermal absorption was a more important pathway for intake of low molecular weight PAHs than inhalation. PMID- 29790337 TI - Copper(I)-USY as a Ligand-Free and Recyclable Catalyst for Ullmann-Type O-, N-, S , and C-Arylation Reactions: Scope and Application to Total Synthesis. AB - The copper(I)-doped zeolite CuI-USY proved to be a versatile, efficient, and recyclable catalyst for various Ullmann-type coupling reactions. Easy to prepare and cheap, this catalytic material enables the arylation and heteroarylation of diverse O-, N-, S-, and C-nucleophiles under ligand-free conditions while exhibiting large functional group compatibility. The facility of this catalyst to promote C-O bond formation was further demonstrated with the total synthesis of 3 methylobovatol, a naturally occurring diaryl ether of biological relevance. From a mechanistic viewpoint, two competitive pathways depending on the nature of the nucleophile and consistent with the obtained results have been proposed. PMID- 29790338 TI - Improvement of the Heat Resistance of Prussian Blue Nanoparticles in a Clay Film Composed of Smectite Clay and epsilon-Caprolactam. AB - Prussian blue (PB) is limited in its application by its breakdown at elevated temperatures. To improve the heat resistance of PB, we prepared a composite film comprising PB nanoparticles (NPs), smectite clay, and an organic compound. The composite film had a microstructure in which PB NPs were intercalated between smectite/organic compound layers. The predominant oxidation temperature of the PB NPs in the composite film was around 500 degrees C in air, higher than the oxidation temperature of bulk PB in air (250 degrees C). This improvement in the oxidation temperature may be due to the composite film acting as a barrier to oxygen gas. These results indicate the effectiveness of clay materials for the improvement of heat resistance for low-temperature decomposition compounds, not only PB but also other porous coordination polymers. PMID- 29790341 TI - Transition-Metal-Free Access to Pyridocarbazoles from 2-Alkynylindole-3 carbaldehydes via Azomethine Ylide. AB - An efficient approach for the synthesis of functionalized tetrahydro pyrido/quinolinocarbazoles from 2-alkynylindole-3-carbaldehydes and l-proline utilizing a metal-free decarboxylative cyclization, ring expansion, and ring contraction strategy via the generation of azomethine ylide was developed. The reaction of 2-alkynylindole-3-carbaldehydes with l-thioproline leads to the formation of gamma-carbolines. By virtue of this expedient method, a diverse range of biologically active heteroannulated carbazoles can be synthesized efficiently. PMID- 29790340 TI - alpha-Diimines as Versatile, Derivatizable Ligands in Ruthenium(II) p-Cymene Anticancer Complexes. AB - alpha-Diimines are among the most robust and versatile ligands available in synthetic coordination chemistry, possessing finely tunable steric and electronic properties. A series of novel cationic ruthenium(II) p-cymene complexes bearing simple alpha-diimine ligands, [(eta6- p-cymene)RuCl{kappa2 N-(HCNR)2}]NO3 (R = Cy, [1]NO3; R = 4-C6H10OH, [2]NO3; R = 4-C6H4OH, [3]NO3), were prepared in near quantitative yields as their nitrate salts. [2]NO3 displays high water solubility. The potential of the alpha-diimine ligand in [3]NO3 as a carrier of bioactive molecules was investigated via esterification reactions with the hydroxyl groups. Thus, the double-functionalized derivatives [(eta6- p cymene)RuCl{kappa2 N-(HCN(4-C6H4OCO-R))2}]NO3 (R = aspirinate, [5]NO3; valproate, [6]NO3) and also [4]Cl (R = Me) were obtained in good-to-high yields. UV-vis and multinuclear NMR spectroscopy and cyclic voltammetric studies in aqueous solution revealed only minor ruthenium chloride hydrolytic cleavage, biologically accessible reduction potentials, and pH-dependent behavior of [3]NO3. Density functional theory analysis was performed in order to compare the Ru-Cl bond strength in [1]+ with the analogous ethylenediamine complex, showing that the higher stability observed in the former is related to the electron-withdrawing properties of the alpha-diimine ligand. In vitro cytotoxicity studies were performed against tumorigenic (A2780 and A2780cisR) and nontumorigenic (HEK-293) cell lines, with the complexes bearing simple alpha-diimine ligands ranging from inactive to IC50 values in the low micromolar range. The complexes functionalized with bioactive components, i.e., [5]NO3 and [6]NO3, exhibited a marked increase in the cytotoxicity with respect to the precursor [3]NO3. PMID- 29790339 TI - Highly Oriented Monolayer Graphene Grown on a Cu/Ni(111) Alloy Foil. AB - Fast-growth of single crystal monolayer graphene by CVD using methane and hydrogen has been achieved on "homemade" single crystal Cu/Ni(111) alloy foils over large area. Full coverage was achieved in 5 min or less for a particular range of composition (1.3 at.% to 8.6 at.% Ni), as compared to 60 min for a pure Cu(111) foil under identical growth conditions. These are the bulk atomic percentages of Ni, as a superstructure at the surface of these foils with stoichiometry Cu6Ni1 (for 1.3 to 7.8 bulk at.% Ni in the Cu/Ni(111) foil) was discovered by low energy electron diffraction (LEED). Complete large area monolayer graphene films are either single crystal or close to single crystal, and include folded regions that are essentially parallel and that were likely wrinkles that "fell over" to bind to the surface; these folds are separated by large, wrinkle-free regions. The folds occur due to the buildup of interfacial compressive stress (and its release) during cooling of the foils from 1075 degrees C to room temperature. The fold heights measured by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) prove them to all be 3 layers thick, and scanning electron microscopy (SEM) imaging shows them to be around 10 to 300 nm wide and separated by roughly 20 MUm. These folds are always essentially perpendicular to the steps in this Cu/Ni(111) substrate. Joining of well-aligned graphene islands (in growths that were terminated prior to full film coverage) was investigated with high magnification SEM and aberration-corrected high-resolution transmission electron microscopy (TEM) as well as AFM, STM, and optical microscopy. These methods show that many of the "join regions" have folds, and these arise from interfacial adhesion mechanics (they are due to the buildup of compressive stress during cool-down, but these folds are different than for the continuous graphene films-they occur due to "weak links" in terms of the interface mechanics). Such Cu/Ni(111) alloy foils are promising substrates for the large-scale synthesis of single-crystal graphene film. PMID- 29790342 TI - High Permeation Rates in Liposome Systems Explain Rapid Glyphosate Biodegradation Associated with Strong Isotope Fractionation. AB - Bacterial uptake of charged organic pollutants such as the widely used herbicide glyphosate is typically attributed to active transporters, whereas passive membrane permeation as an uptake pathway is usually neglected. For 1-palmitoyl-2 oleoyl- sn-glycero-3-phosphocholine (POPC) liposomes, the pH-dependent apparent membrane permeation coefficients ( Papp) of glyphosate, determined by nuclear magnetic resonance (NMR) spectroscopy, varied from Papp (pH 7.0) = 3.7 (+/-0.3) * 10-7 m.s-1 to Papp (pH 4.1) = 4.2 (+/-0.1) * 10-6 m.s-1. The magnitude of this surprisingly rapid membrane permeation depended on glyphosate speciation and was, at circumneutral pH, in the range of polar, noncharged molecules. These findings point to passive membrane permeation as a potential uptake pathway during glyphosate biodegradation. To test this hypothesis, a Gram-negative glyphosate degrader, Ochrobactrum sp. FrEM, was isolated from glyphosate-treated soil and glyphosate permeation rates inferred from the liposome model system were compared to bacterial degradation rates. Estimated maximum permeation rates were, indeed, 2 orders of magnitude higher than degradation rates of glyphosate. In addition, biodegradation of millimolar glyphosate concentrations gave rise to pronounced carbon isotope fractionation with an apparent kinetic isotope effect, AKIEcarbon, of 1.014 +/- 0.003. This value lies in the range typical of non-masked enzymatic isotope fractionation demonstrating that glyphosate biodegradation was not subject to mass transfer limitations and glyphosate exchange across the cell membrane was rapid relative to enzymatic turnover. PMID- 29790343 TI - Main-Group-Catalyzed Reductive Alkylation of Multiply Substituted Amines with Aldehydes Using H2. AB - Given the growing demand for green and sustainable chemical processes, the catalytic reductive alkylation of amines with main-group catalysts of low toxicity and molecular hydrogen as the reductant would be an ideal method to functionalize amines. However, such a process remains challenging. Herein, a novel reductive alkylation system using H2 is presented, which proceeds via a tandem reaction that involves the B(2,6-Cl2C6H3)( p-HC6F4)2-catalyzed formation of an imine and the subsequent hydrogenation of this imine catalyzed by a frustrated Lewis pair (FLP). This reductive alkylation reaction generates H2O as the sole byproduct and directly functionalizes amines that bear a remarkably wide range of substituents including carboxyl, hydroxyl, additional amino, primary amide, and primary sulfonamide groups. The synthesis of isoindolinones and aminophthalic anhydrides has also been achieved by a one-pot process that consists of a combination of the present reductive alkylation with an intramolecular amidation and intramolecular dehydration reactions, respectively. The reaction showed a zeroth-order and a first-order dependence on the concentration of an imine intermediate and B(2,6-Cl2C6H3)( p-HC6F4)2, respectively. In addition, the reaction progress was significantly affected by the concentration of H2. These results suggest a possible mechanism in which the heterolysis of H2 is facilitated by the FLP comprising THF and B(2,6-Cl2C6H3)( p HC6F4)2. PMID- 29790344 TI - A Thermal Diode Based on Nanoscale Thermal Radiation. AB - In this work we demonstrate thermal rectification at the nanoscale between doped Si and VO2 surfaces. Specifically, we show that the metal-insulator transition of VO2 makes it possible to achieve large differences in the heat flow between Si and VO2 when the direction of the temperature gradient is reversed. We further show that this rectification increases at nanoscale separations, with a maximum rectification coefficient exceeding 50% at ~140 nm gaps and a temperature difference of 70 K. Our modeling indicates that this high rectification coefficient arises due to broadband enhancement of heat transfer between metallic VO2 and doped Si surfaces, as compared to narrower-band exchange that occurs when VO2 is in its insulating state. This work demonstrates the feasibility of accomplishing near-field-based rectification of heat, which is a key component for creating nanoscale radiation-based information processing devices and thermal management approaches. PMID- 29790345 TI - Characterization of the Major Odor-Active Compounds in Dry Jujube Cultivars by Application of Gas Chromatography-Olfactometry and Odor Activity Value. AB - The volatile compounds of jujube ( Ziziphus jujube Mill.) puree obtained from three cultivars, 'Jinsixiaozao' (Y1), 'Youzao' (Y2), and 'Yuzao' (Y3), were analyzed by gas chromatography-olfactometry (GC-O), gas chromatography-mass spectrometry, gas chromatography-flame photometric detection, and a nitrogen phosphorus detector. The results showed that a total of 37, 37, and 35 odor active compounds were identified by GC-O in samples of Y1, Y2, and Y3, respectively. In addition, the odor activity value (OAV) was used to determine the important compounds. The results demonstrated that hexanal (OAV of 39-85), ( E)-2-octenal (OAV of 32-70), beta-damascenone (OAV of 14-49), ethyl hexanoate (OAV of 22-39), 3-mercaptohexyl acetate (OAV of 17-24), and 2,5-dimethylpyrazine (OAV of 17-22) were key odor-active compounds. It is of great significance to develop high-grade jujube food by determining key odor-active compounds. Furthermore, four volatiles (hexanal, 1-octen-3-ol, 3-mercapohexyl acetate, and benzaldehyde) reduced the overall threshold value by 2.36, 1.01, 1.34, and 1.19, respectively. PMID- 29790346 TI - Ligand-Free Iron-Catalyzed Carbon(sp2)-Carbon(sp2) Cross-Coupling of Alkenyllithium with Vinyl Halides. AB - An efficient ligand-free iron-catalyzed cross-coupling reaction involving alkenyllithium and vinyl iodides was developed to form diene species in moderate to good yields. This new iron-catalyzed cross-coupling reaction provides a mild, inexpensive, and environmentally friendly avenue toward synthesis of diversified diene derivatives. PMID- 29790347 TI - Hydrophobic Collapse of Ubiquitin Generates Rapid Protein-Water Motions. AB - We report time-resolved measurements of the coupled protein-water modes of solvated ubiquitin during protein folding. Kinetic terahertz absorption (KITA) spectroscopy serves as a label-free technique for monitoring large scale conformational changes and folding of proteins subsequent to a sudden T-jump. We report here KITA measurements at an unprecedented time resolution of 500 ns, a resolution 2 orders of magnitude better than those of any previous KITA measurements, which reveal the coupled ubiquitin-solvent dynamics even in the initial phase of hydrophobic collapse. Complementary equilibrium experiments and molecular simulations of ubiquitin solutions are performed to clarify non equilibrium contributions and reveal the molecular picture upon a change in structure, respectively. On the basis of our results, we propose that in the case of ubiquitin a rapid (<500 ns) initial phase of the hydrophobic collapse from the elongated protein to a molten globule structure precedes secondary structure formation. We find that these very first steps, including large-amplitude changes within the unfolded manifold, are accompanied by a rapid (<500 ns) pronounced change of the coupled protein-solvent response. The KITA response upon secondary structure formation exhibits an opposite sign, which indicates a distinct effect on the solvent-exposed surface. PMID- 29790348 TI - Bioinspired Photocatalytic Shark-Skin Surfaces with Antibacterial and Antifouling Activity via Nanoimprint Lithography. AB - By combining antifouling shark-skin patterns with antibacterial titanium dioxide (TiO2) nanoparticles (NPs), we present a simple route toward producing durable multifunctional surfaces that decrease microbial attachment and inactivate attached microorganisms. Norland Optical Adhesive, a UV-crosslinkable adhesive material, was loaded with 0, 10, or 50 wt % TiO2 NPs from which shark-skin microstructures were imprinted using solvent-assisted soft nanoimprint lithography on a poly(ethylene terephthalate) (PET) substrate. To obtain coatings with an exceptional durability and an even higher concentration of TiO2 NPs, a solution containing 90 wt % TiO2 NPs and 10 wt % tetraethyl orthosilicate was prepared. These ceramic shark-skin-patterned surfaces were fabricated on a PET substrate and were quickly cured, requiring only 10 s of near infrared (NIR) irradiation. The water contact angle and the mechanical, antibacterial, and antifouling characteristics of the shark-skin-patterned surfaces were investigated as a function of TiO2 composition. Introducing TiO2 NPs increased the contact angle hysteresis from 30 to 100 degrees on shark-skin surfaces. The hardness and modulus of the films were dramatically increased from 0.28 and 4.8 to 0.49 and 16 GPa, respectively, by creating ceramic shark-skin surfaces with 90 wt % TiO2 NPs. The photocatalytic shark-skin-patterned surfaces reduced the attachment of Escherichia coli by ~70% compared with smooth films with the same chemical composition. By incorporating as low as 10 wt % TiO2 NPs into the chemical matrix, over 95% E. coli and up to 80% Staphylococcus aureus were inactivated within 1 h UV light exposure because of the photocatalytic properties of TiO2. The photocatalytic shark-skin-patterned surfaces presented here were fabricated using a solution-processable and roll-to-roll compatible technique, enabling the production of large-area high-performance coatings that repel and inactivate bacteria. PMID- 29790349 TI - High-Pressure Phase Relations and Crystal Structures of Postspinel Phases in MgV2O4, FeV2O4, and MnCr2O4: Crystal Chemistry of AB2O4 Postspinel Compounds. AB - We have investigated high-pressure, high-temperature phase transitions of spinel (Sp)-type MgV2O4, FeV2O4, and MnCr2O4. At 1200-1800 degrees C, MgV2O4 Sp decomposes at 4-7 GPa into a phase assemblage of MgO periclase + corundum (Cor) type V2O3, and they react at 10-15 GPa to form a phase with a calcium titanite (CT)-type structure. FeV2O4 Sp transforms to CT-type FeV2O4 at 12 GPa via decomposition phases of FeO wustite + Cor-type V2O3. MnCr2O4 Sp directly transforms to the calcium ferrite (CF)-structured phase at 10 GPa and 1000-1400 degrees C. Rietveld refinements of CT-type MgV2O4 and FeV2O4 and CF-type MnCr2O4 confirm that both the CT- and CF-type structures have frameworks formed by double chains of edge-shared B3+O6 octahedra (B3+ = V3+ and Cr3+) running parallel to one of orthorhombic cell axes. A relatively large A2+ cation (A2+ = Mg2+, Fe2+, and Mn2+) occupies a tunnel-shaped space formed by corner-sharing of four double chains. Effective coordination numbers calculated from eight neighboring oxygen A2+ cation distances of CT-type MgV2O4 and FeV2O4 and CF-type MnCr2O4 are 5.50, 5.16, and 7.52, respectively. This implies that the CT- and CF-type structures practically have trigonal prism (six-coordinated) and bicapped trigonal prism (eight-coordinated) sites for the A2+ cations, respectively. A relationship between cation sizes of VIIIA2+ and VIB3+ and crystal structures (CF- and CT types) of A2+B23+O4 is discussed using the above new data and available previous data of the postspinel phases. We found that CF-type A2+B23+O4 crystallize in wide ionic radius ranges of 0.9-1.4 A for VIIIA2+ and 0.55-1.1 A for VIB3+, whereas CT-type phases crystallize in very narrow ionic radius ranges of ~0.9 A for VIIIA2+ and 0.6-0.65 A for VIB3+. This would be attributed to the fact that the tunnel space of CT-type structure is geometrically less flexible due to the smaller coordination number for A2+ cation than that of CF-type. PMID- 29790350 TI - Glutaredoxin Deletion Shortens Chronological Life Span in Saccharomyces cerevisiae via ROS-Mediated Ras/PKA Activation. AB - Glutaredoxins (GRXs), small redox proteins that use reduced glutathione as an electron donor, are key components of the cellular antioxidant system. In this study, we used Saccharomyces cerevisiae as a model system to investigate the effects of GRX deletion on yeast chronological life span (CLS). Deletion of either Grx1 or Grx2 shortened yeast CLS. Quantitative proteomics revealed that GRX deletion decreased the expression of stress-response proteins, leading to increased cellular reactive oxygen species accumulation and, subsequently, intracellular acidification. This activated the Ras/protein kinase A (PKA) signaling pathway. Genetic and biochemical analyses demonstrated that Ras/PKA activation decreased stress resistance and increased biosynthesis, requiring yeast cells to grow under unfavorable conditions and resulting in a shortened CLS. Our results provided new insights into mechanisms underlying exacerbation of the aging process by oxidative stress. PMID- 29790351 TI - Light Absorption Coefficient of CsPbBr3 Perovskite Nanocrystals. AB - Inductively coupled plasma mass spectrometry (ICP-MS) was combined with UV-vis absorption spectroscopy and transmission electron microscopy to determine the size, composition, and intrinsic absorption coefficient MUi of 4 to 11 nm sized colloidal CsPbBr3 nanocrystals (NCs). The ICP-MS measurements demonstrate the nonstoichiometric nature of the NCs, with a systematic excess of lead for all samples studied. Rutherford backscattering measurements indicate that this enrichment in lead concurs with a relative increase in the bromide content. At high photon energies, MUi is independent of the nanocrystal size. This allows the nanocrystal concentration in CsPbBr3 nanocolloids to be readily obtained by a combination of absorption spectroscopy and the CsPbBr3 sizing curve. PMID- 29790352 TI - Constructing Sensitive and Fast Lead-Free Single-Crystalline Perovskite Photodetectors. AB - We developed a high-performance photodetector based on (CH3NH3)3Sb2I9 (MA3Sb2I9) microsingle crystals (MSCs). The MA3Sb2I9 single crystals exhibit a low-trap state density of ~1010 cm-3 and a long carrier diffusion length reaching 3.0 MUm, suggesting its great potential for optoelectronic applications. However, the centimeter single crystal (CSC)-based photodetector exhibits low responsivity (10 6 A/W under 1 sun illumination) due to low charge-carrier collection efficiency. By constructing the MSC photodetector with efficient charge-carrier collection, the responsivity can be improved by three orders of magnitude (under 1 sun illumination) and reach 40 A/W with monochromatic light (460 nm). Furthermore, the MSC photodetectors exhibit fast response speed of <1 ms, resulting in a high gain of 108 and a gain-bandwidth product of 105 Hz. These numbers are comparable to the lead-perovskite single-crystal-based photodetectors. PMID- 29790353 TI - [Back pain treatment]. AB - Spine pain is one of the most common medical problems. Yearly incidence is reported between 15 and 45 %, lifelong is 60-90 %. Neurological examination, radiology examination, CT or magnetic resonance imaging are the basic diagnostics. Acute back pain is usually treated monotherapeutically, NSAIDs is the base. Chronic back pain treatment is multidisciplinary, it combines pharmacotherapy, physiotherapy, psychotherapy and other methods. In pharmacotherapy we proceed according to the WHO three-step ladder, including strong opioid medication for strong back pain. Neuropathic component of pain is usually eased with antidepressants or anticonvulsants. PMID- 29790354 TI - [Opioids and new trends in pain therapy]. AB - Opioids are well known for their ability to reduce the perception of pain without a loss of consciousness. However, the influence of opioids on organism is very complex. Clinical pharmacology of currently available opioid analgesics is determined by three major factors - their opioid receptor properties, pharmacokinetic properties and genetic polymorphism in the opiate receptor and cytochrome P450 isoform. In acute severe pain are opioids very efficient. Long term experience with opioid analgesia in patients with cancer pain has shown high favorable risk/benefit ratio. However, the treatment with opioids has its issues. Life expectancy of chronic pain patients is temporarily unlimited and for that reason the time horizon of opioid therapy is unlimited as well. In comparison with cancer pain opioid responsiveness to chronic non-cancer pain is somewhat different. Clinical experience has shown that exceeding of medium-sized doses of opioids in the treatment of chronic non-cancer pain does not lead to further improvement of analgesia, but only increases degree of physical dependency and tolerance. The most important step is to choose the right patient. Subsequently, the success of opioid therapy depends on a careful search of balance between pain, opioid dosage and analgesia with emphasis on individualization and attention to the prevention and management of side effects. PMID- 29790355 TI - [Pathophysiology of pain and its clinical application]. AB - The article describes the pathophysiology of both acute and chronic pain. Some common mechanisms of chronic pain, including somatic and visceral pains, are highlighted. There are also some painful syndromes and their pathophysiological mechanisms with a direct relationship to their treatment. In addition to the basic pharmacotherapeutic options resulting from the pathophysiology of pain, new possibilities of pain therapy are also mentioned, especially the neuromodulatory and neurostimulatory methods again from the point of view of pathophysiological principles. Therapies also include psychotherapy and placebo effect with the point of evidence-based medicine. PMID- 29790356 TI - [Non-opioid analgesics]. AB - Non-opioid analgesics are commonly used to treat mild and moderate acute and chronic pain. They can be used as monotherapy; however, they have greater efficacy in combination with weak and strong opioids. Unlike opioids, long-term use of non-steroidal anti-inflammatory drugs does not lead to physical dependence. One of the main disadvantages of the NSA is the risk of gastrointestinal side effects, especially bleeding into the digestive tract. This is increased especially in ulcerative disease and in higher doses, but also in the elderly (over 65 years), also with concomitant administration of corticosteroids, anticoagulants or other NSAIDs. PMID- 29790357 TI - [Control (editing) of the genome within reach, or already in our hands?] AB - Although different genome editing tools have been around for decades, the recent emergence of cheap, quick, and accessible CRISPR/Cas9 technology has led to a revolution in this field. The technique has the potential to transform medicine from curative into preventive using a gene therapy. An application of genome editing has proven to be effective for both genetic and non-genetic (e.g. infectious) diseases. However, cancer and rare diseases treatment is at the forefront of interest. Concurrently, the legal and ethical frameworks should be discussed, especially as the technology moves towards a modification of the germ cells or embryos. In addition to a precise molecular genetic diagnosis and choosing the best gene therapy approach for a particular individual, an attention should also be paid to the impacts on the entire human population and the next generations. In this review, we summarize the most important applications of CRISPR/Cas9 technology in the field of medicine. Some interesting results from recent years are presented in the context of used approaches and importance for the future developments in medicine. Finally, ethical and legal conditions in relation to different gene editing applications are discussed. PMID- 29790358 TI - [Esophagogastric junction and its tumours - comments to definition and classification]. AB - In spite of the worldwide decreasing incidence of gastric cancer the number of esophagogastric junction and proximal third of stomach carcinomas has been gradually growing up. The reason of that is an increasing incidence of reflux esophagitis with Barrett's metaplasia and a successful eradication of Helicobacter pylori infection. The aim of this work is to provide various views on definition of the esophagogastric junction and to give an overview of tumours classification schemes being used. PMID- 29790359 TI - [Hereditary breast cancer: genetic etiology and current possibilities of prevention and surgical treatment]. AB - Cancer is the second most common cause of death in our population just after cardiovascular diseases, since each third individual will become affected by it during their lifetime. Breast cancer is the most common malignancy in women. The lifetime cumulative risk of breast cancer in women under the age of 75 is around 8 % according to Czech statistics. In 70-75 % of all individuals sporadic breast carcinomas are found, with 5-10 % of all women suffer from the hereditary breast and ovarian cancer (HBOC) syndrome. Radical, bilateral, removal of the mammary gland is the most effective prevention of breast cancer in BRCA positive women. We present a summary of 37 BRCA positive Czech patients who underwent prophylactic bilateral mastectomy and whose mean age was 46.5 years. Surgical solution is currently the only effective therapeutic way to prevent breast cancer in BRCA positive women with high genetic risk. The cosmetic consequences of this radical surgery can be solved through many reconstruction tasks. PMID- 29790360 TI - [Current and future pharmacotherapy of severe psychiatric disorders]. AB - Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring, but also implementation of general trends into the clinical practice. New pharmacological options include drugs aimed at other than monoaminergic systems and old drugs used before the psychopharmacological era. In pharmacoresistant depression promising options include switch to new multimodal/multifunctional antidepressants, augmentation with new atypical antipsychotics (cariprazine and brexpiprazole) and adjunctive treatment with anti-inflammatory and anti-apoptotic agents and nutraceuticals. Ketamine, opioids and psychedelics are in different phases of clinical testing. Recent advances in technology and emerging knowledge about the dysfunctional brain circuits and neuroplasticity have led to the development of different new neuromodulation techniques usually used as add-on therapy. In schizophrenia the cornerstone of the current treatment is still antipsychotic medications. In addition to aripiprazole two new partial dopamine agonists, brexpiprazole and cariprazine are now available. Especially the group of partial dopamine agonists is in the center of interest. Due to severe consequences of partial adherence, new formulations of long-acting injections of the second-generation antipsychotics with longer interval of application have been developed (3- month paliperidone palmitate). New treatment options not yet available include cannabidiol, glutamate modulators and nicotine receptors agonists. PMID- 29790361 TI - Anti-bacterial effects of components from Sanguisorba officinalis L. on Vibrio vulnificus and their soluble epoxide hydrolase inhibitory activity. AB - Sanguisorba officinalis L. is a traditional herbal medicine, which is prevailingly applied to cure hemorrhoids, wounds and ulcers in Eastern Asian countries. The purpose of this study was to investigate the antibacterial and soluble epoxide hydrolase (sEH) inhibitory effects of the extracts and components from S. officinalis. The methanol extract was divided into ethyl acetate (EtOAc), n-butanol (n-BuOH), and water layers. In our screening procedure, the EtOAc and n BuOH extracts and compounds (1-2) remarkably suppressed the growth of V. vulnificus in a dose-dependent manner. In addition, the EtOAc extract and compound 1 exhibited significant inhibitory effect on the V. vulnificus induced cytotoxicity on HeLa cells. Furthermore, compound 4 displayed an inhibition against sEH with an IC50 value of 7.0 +/- 0.5 MUM. A kinetic analysis demonstrated that the inhibitory effect of compound 4 was a mixed type, with an inhibitory constant (Ki) 0.22 +/- 0.0 MUM. PMID- 29790362 TI - The Untold Advantages of Retzius-Sparing Robotic Radical Prostatectomy. PMID- 29790363 TI - Editorial Comment on: How Reliable Is the Intraoperative Assessment of Residual Fragments During Percutaneous Nephrolithotomy? A Prospective Study by Nevo et al. PMID- 29790364 TI - Editorial Comment on: Effect of Mannitol on Ultrasonographically Measured Optic Nerve Sheath Diameter as a Surrogate for Intracranial Pressure During Robot Assisted Laparoscopic Prostatectomy with Pneumoperitoneum and the Trendelenburg Position by Jun et al. PMID- 29790365 TI - Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with bioprosthetic valves. AB - INTRODUCTION: The non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, apixaban, edoxaban and rivaroxaban, are preferred over vitamin K antagonists for stoke prevention in most patients with non-valvular atrial fibrillation. The NOACs are contraindicated in atrial fibrillation patients with rheumatic mitral stenosis or mechanical heart valves. There is evidence that bioprosthetic heart valves are less thrombogenic than mechanical heart valves, but it is unknown whether the risk of thromboembolism in atrial fibrillation patients with bioprosthetic valves differs from that in patients without such valves. Areas covered: The authors present a review of the efficacy and safety evidence surrounding the use of NOACs for stroke prevention in atrial fibrillation patients with bioprosthetic heart valves. Expert commentary: While the data is limited, there is no significant difference in thromboembolic, and bleeding outcomes in patients with AF and bioprosthetic heart valves treated with NOAC therapy. Future studies are required before definitive conclusions can be drawn regarding the safety and efficacy of NOAC therapy in AF patients bioprosthetic heart valves. PMID- 29790366 TI - Do Illuminated Foot Pedals Improve the Speed and Accuracy of Pedal Activation During Endoscopic Procedures? AB - PURPOSE: Endourologic procedures such as percutaneous nephrolithotomy (PCNL) employ the use of foot pedals in low-light operating room (OR) settings. These pedals can be especially difficult to locate or distinguish when several pedals are present during a single operation. Improper instrument activation in the OR has led to serious complications ranging from unintentional electrocautery to patient burns and even an intraoperative explosion. This study evaluates the impact of color-coded illumination on speed and efficiency of foot pedal activation. MATERIALS AND METHODS: During a simulated PCNL procedure, the foot pedals for a C-arm, laser, and ultrasonic lithotripter (USL) were placed in random positions. Ten participants performed pedal activation in a randomized sequence. Objective outcomes included time to instrument activation, number of attempted pedal presses, number of incomplete pedal presses, and number of incorrect pedal presses. Subjective preferences for pedal illumination were also determined. Data were analyzed using Mann-Whitney U, Wilcoxon signed-rank, and Chi-square tests with p < 0.05 indicating statistical significance. RESULTS: Illuminated foot pedals were associated with decreases in the average activation time for all instruments collectively (3.95 seconds vs 6.49 seconds; p = 0.017) and individually (C-arm: 3.07 seconds vs 4.21 seconds; p = 0.006; laser: 13.04 seconds vs 15.18 seconds; p < 0.001; USL: 3.28 seconds vs 4.91 seconds; p < 0.001) compared with nonilluminated pedals. Illuminated pedals were associated with fewer attempted pedal presses (33.5 vs 39.5; p = 0.007) and incomplete pedal presses (1.5 vs 8.5; p = 0.002). The number of incorrect pedal presses decreased with illumination, but this did not reach statistical significance (0 vs 0.5; p = 0.08). Participants reported that illumination simplified pedal activation and recommended its use (p < 0.01). CONCLUSION: Color-coded illumination improved the speed and efficiency of foot pedal activation during simulated PCNL. Participants subjectively preferred using illuminated foot pedals for endourologic procedures and felt that they improved safety and efficiency. PMID- 29790368 TI - E-iatrogenesis: Unnecessary Ordering of Urine Creatine. PMID- 29790367 TI - Are Hydroethidine-Based Probes Reliable for Reactive Oxygen Species Detection? AB - Detection and quantification of the highly reactive and short-lived superoxide (O*2-) can be challenging. Here, we present a new mass spectrometry (MS)-based method to detect and quantify O*2- using three fluorogenic hydroethidine probes: hydroethidine (HE), mito-hydroethidine (mito-HE), and hydropropidine (HPr+), which measure cytosolic, mitochondrial, and extracellular O*2-, respectively. The probes and their oxidation products were simultaneously quantified by applying multiple reaction monitoring (MRM) with MS that allowed the specific measurement of reactive oxygen species (ROS) distribution within the cell. The advantage of this liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is that coeluting compounds can be precisely distinguished using specific precursor and fragment masses. This method overcomes limitations from spectral overlap of O*2- specific and nonspecific products in fluorescence spectra or the low specificity associated with chromatography-based approaches. However, our experiments showed that these HE probes can be prone to autoxidation during incubation at 37 degrees C in Hank's solution. Cell treatments with strong oxidants did not significantly increase levels of the O*2- radical. Thus, subtle changes in ROS levels in cell culture experiments might not be quantifiable. Our findings raise the question of whether HE-based probes can be used for the reliable detection of O*2- radicals in cell culture. Antioxid. Redox Signal. 00, 000-000. PMID- 29790369 TI - An Innovative Perioperative Pain Program for Chronic Opioid Users: An Academic Medical Center's Response to the Opioid Crisis. AB - Increased utilization of prescription opioids for pain management has led to a nationwide public health crisis with alarming rates of addiction and opioid related deaths. In the surgical setting, opioid prescriptions have been implicated as a contributing factor to the opioid epidemic. The authors developed an innovative model to address aspects of pain management and opioid utilization during preoperative evaluation, acute surgical hospitalization, and postoperative follow-up for chronic opioid users. This program involves multidisciplinary teams that include acute and chronic pain specialists, psychiatrists, integrative medicine specialists, and physical medicine and rehabilitation services. It also features a novel infrastructure for triage and pain management education and treatment. Individualized patient plans are devised that can include preoperative opioid weaning, regional anesthesia that minimizes opioid use, and multimodal techniques for surgical pain treatment. Multidisciplinary programs such as this have the potential to both improve perioperative pain control and prevent escalation of opioid use among chronic opioid users. PMID- 29790370 TI - Environmental Factors on Facebook Reviews: Using Social Media as Feedback to Improve Hospital Quality. PMID- 29790371 TI - Clinical Quality and Patient Experience in the Adult Ambulatory Setting. AB - Quality and patient experience are important dimensions of care delivery. The extent to which they are related in the adult outpatient setting is unknown. This brief study utilized data from a large integrated health system over a 1-year period in 2015 and measured the degree of correlation between physicians' patient experience scores and 8 standardized quality metrics. These quality measures were paired into similar groups to create 4 composite measures: outcome, screening, vaccination, and adherence. Measures of outcome ( r = 0.20, P = .06), vaccination ( r = 0.12, P = .26), and adherence ( r = -0.04, P = .75) were not significantly correlated with patient experience; screening ( r = 0.29, P = .006) was minimally correlated with patient experience. Overall, this study found minimal correlation between measures of patient experience and clinical quality in the outpatient setting. Measurement of both of these domains is essential to understanding patterns of care. PMID- 29790372 TI - Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation. AB - OBJECTIVE: Rheumatoid arthritis (RA) is associated with chronic inflammation. The suppression of inflammation is key to the treatment of RA. Glucocorticoids (GCs) are classical anti-inflammatory drugs with several disadvantages such as poor water solubility and low specificity in the body. These disadvantages are the reasons for the quick elimination and side effects of GCs in vivo. Micelles are ideal carriers for GCs delivery to inflamed synovium. We set out to improve the targeting and pharmacokinetic profiles of GCs by preparing a targeting micelle system. METHODS: In this study, natural chlosterol (CC) and folic acid (FA) were used to fabricate polysialic acid (PSA) micelles for the targeted delivery of Dexamethasone (Dex). The biodistribution and therapeutic efficacy of the resulting micelles were evaluated in vitro and in vivo. RESULTS: PSA-CC and FA PSA-CC micelles showed a size below 100 nm and a moderate negative charge. PSA-CC and FA-PSA-CC micelles could also enhance the intracellular uptake of Dex and the suppression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vitro and in vivo. Arthritis mice showed reduced paw thickness and clinical arthritis index using PSA-CC and FA-PSA-CC micelle treatment. Micellized Dex demonstrated a 4 ~ 5 fold longer elimination half-life and a 2 ~ 3 folds higher bioavailability than commercial Dex injection. FA modification significantly improved the anti-inflammatory efficacy of PSA-CC micelles. CONCLUSION: FA-PSA-CC micelles demonstrated significant advantages in terms of the suppression of inflammation and the treatment of inflammatory arthritis. These reliable and stable micelles possess a high potential to be transferred for clinical use. PMID- 29790374 TI - Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer. AB - Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells. PMID- 29790375 TI - Trifecta Outcomes in Multifocal Tumors: A Comparison Between Robotic and Open Partial Nephrectomy. AB - OBJECTIVES: To report a comparative analysis of outcomes in patients who underwent multiple excisions for unilateral synchronous multifocal renal tumors using both open and robotic approaches. METHODS: We retrospectively reviewed 110 patients who underwent robotic and open partial nephrectomy and had multiple tumor excisions in an ipsilateral kidney. "Trifecta" was defined as negative surgical margins, no urologic complications, and a glomerular filtration rate (GFR) preservation of >=90% at last follow-up. Inverse probability of treatment weighting (IPTW) was applied to equilibrate treatment groups, minimize selection bias, and optimize inference on the basis of each patient's clinicodemographic characteristics. RESULTS: Sixty-eight robotic and 42 open patient approaches had sufficient data for IPTW. After weighting, there were no statistical differences in baseline characteristics between the two groups. On adjusted analyses, robotic partial nephrectomy achieved equivalent rates of trifecta to open surgery (16.3% vs 16.5%, p = 0.99), which persisted on subgroup analyses of patients with two (20.1% vs 23.7%, p = 0.82) or more than two tumors (6.8% vs 7.4%, p = 0.95). There were no differences between robotic and open cohorts for negative margin rates, absence of complications, or GFR >=90%. The robotic cohort had a shorter mean length of stay (3.4 vs 4.9 days, p < 0.001). CONCLUSIONS: Surgical resection remains the mainstay for patients with unilateral, synchronous, and multifocal renal tumors. Our analysis found that both open and robotic approaches to partial nephrectomy are equally likely to achieve the "trifecta" outcome in an equilibrated high-risk group of patients. The robotic approach for these complex patients may be safe and feasible for a carefully selected group of patients. PMID- 29790373 TI - Non-clinical studies of progesterone. AB - Progesterone is a steroid hormone that is essential for the regulation of reproductive function. Progesterone has been approved for several indications including the treatment of anovulatory menstrual cycles, assisted reproductive technology, contraception during lactation and, when combined with estrogen, for the prevention of endometrial hyperplasia in postmenopausal hormonal therapy. In addition to its role in reproduction, progesterone regulates a number of biologically distinct processes in other tissues, particularly in the nervous system. This physiological hormone is poorly absorbed when administered in a crystalline form and is not active when given orally, unless in micronized form, or from different non-oral delivery systems that allow a more constant delivery rate. A limited number of preclinical studies have been conducted to document the toxicity, carcinogenicity and overall animal safety of progesterone delivered from different formulations, and these rather old studies showed no safety concern. More recently, it has been shown in animal experiments that progesterone, its metabolite allopregnanolone and structurally related progestins have positive effects on neuroregeneration and repair of brain damage, as well as myelin repair. These recent preclinical findings have the potential to accelerate therapeutic translation for multiple unmet neurological needs. PMID- 29790377 TI - Cross-Cultural Differences in the Experience of Grandparent-Grandchild Relationships and Related Psychosocial Outcomes. AB - This study examined grandchildren's perceptions of the quality of their relationship with their grandmothers and how these perceptions relate to psychosocial outcomes. Eighty-two youth from Mexico and 99 youth from the United States aged between 13 and 16 participated. Results suggested that both cultures benefit in unique ways from positive relationship with their grandmothers. Yet, there were also differences in the relational experience of grandmother grandchild relationships across cultures. Specifically, grandchildren in the U.S. sample reported higher relationship quality, relational competency, and self efficacy than the grandchildren in the Mexico sample. Within the U.S. sample, relationship quality was associated with grandchildren's relational competence, while in the Mexico sample, relationship quality was associated with self efficacy. Limitations of the present study include restricted generalizability to other age groups and to grandfathers and that only one element of the grandparent grandchild dyad was sampled. Longitudinal research will improve our understanding of the causal dynamics of grandparent-grandchild relationships. PMID- 29790376 TI - Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine. AB - Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments. In addition, based on the results of 16S rRNA analysis of feces in rats after acute plateau, we first confirmed that the plateau environment could cause changes in the number and composition of intestinal microbes. More importantly, these changes in flora could lead to a slower metabolic activity of nifedipine in the body after an acute plateau, resulting in increased bioavailability and therapeutic efficacy of nifedipine. Our research will provide basis and new ideas for changes in the fecal flora of human acutely entering the plateau, and contribute to rational drug use of nifedipine. PMID- 29790378 TI - Effect of Human Wnt10b Transgene Overexpression on Peri-Implant Osteogenesis in Ovariectomized Rats. AB - This study aimed to investigate the efficacy of human Wnt10b (hWnt10b) transgene expression in ovariectomized (OVX) rats to accelerate osseointegration around titanium implants, and to provide a new strategy for treating osteoporosis with implants. An in vivo osteoporosis model was generated via bilateral ovariectomy in rats, and changes in expression of Wnt pathway-related genes were investigated. In OVX rats with a femur defect, hWnt10b expressed from an adenovirus vector was locally delivered to the defect site prior to implant placement. Surrounding femur tissues were collected 1 and 3 weeks after implantation for imaging, biomechanical testing, and molecular and histological analyses. In an in vitro model, bone-marrow stromal cells (BMSCs) transfected with adenovirus containing hWnt10b (Ad-hWnt10b) were cultured for 2 weeks in adipogenic medium followed by 2 weeks in osteogenic induction medium. Alizarin Red staining and Oil Red O staining, as well as reverse transcription polymerase chain reaction and Western blot analyses, were performed to assess the effect of hWnt10b expression on BMSC differentiation. Expression of Wnt pathway genes was significantly downregulated in OVX rats. OVX rats treated with Ad-hWnt10b prior to induction of a femur defect showed markedly increased ALP, Runx-2, and osteocalcin expression and decreased cathepsin K expression. Histological and imaging analysis showed increases in the number of osteocalcin-positive cells and the density of newly formed bone surrounding the implant in the Ad-hWnt10b group relative to the untreated control. Meanwhile, Ad-hWnt10b-BMSCs showed significantly increased osteogenesis and decreased adipogenesis. hWnt10b may accelerate osseointegration around implants and subsequently enhance bone regeneration and implant stabilization under OVX conditions. PMID- 29790379 TI - A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer? AB - SIGNIFICANCE: Hydrogen sulfide (H2S) has been recognized as the third gaseous transmitter alongside nitric oxide and carbon monoxide. In the past decade, numerous studies have demonstrated an active role of H2S in the context of cancer biology. Recent Advances: The three H2S-producing enzymes, namely cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), have been found to be highly expressed in numerous types of cancer. Moreover, inhibition of CBS has shown anti-tumor activity, particularly in colon cancer, ovarian cancer, and breast cancer, whereas the consequence of CSE or 3MST inhibition remains largely unexplored in cancer cells. Intriguingly, H2S donation at high amounts or a long time duration has also been observed to induce cancer cell apoptosis in vitro and in vivo while sparing noncancerous fibroblast cells. Therefore, a bell-shaped model has been proposed to explain the role of H2S in cancer development. Specifically, endogenous H2S or a relatively low level of exogenous H2S may exhibit a pro-cancer effect, whereas exposure to H2S at a higher amount or for a long period may lead to cancer cell death. This indicates that inhibition of H2S biosynthesis and H2S supplementation serve as two distinct ways for cancer treatment. This paradoxical role of H2S has stimulated the enthusiasm for the development of novel CBS inhibitors, H2S donors, and H2S-releasing hybrids. CRITICAL ISSUES: A clear relationship between H2S level and cancer progression remains lacking. The possibility that the altered levels of these byproducts have influenced the cell viability of cancer cells has not been excluded in previous studies when modulating H2S producing enzymes. FUTURE DIRECTIONS: The consequence of CSE or 3MST inhibition in cancer cells need to be examined in the future. Better portrayal of the crosstalk among these gaseous transmitters may not only lead to an in-depth understanding of cancer progression but also shed light on novel strategies for cancer therapy. Antioxid. Redox Signal. 00, 000-000. PMID- 29790380 TI - Application of phenolic compounds as natural dye extracted from date-pits: dyeing studies of modified acrylic fibres. AB - This research work involves the dyeing of acrylic fabric with natural dye extracted from date pits powders using Soxhlet extraction process. The effect of dye bath pH, salt concentration, dyeing time and temperature were studied. The optimal dyeing conditions where pH 4, 0 g/L salt, 60 min, and 80 degrees C. The COD and the BOD5 of the residual dye bath were measured and it was shown from the registered values that the residual dye bath presents an acceptable rate of organic discharge. PMID- 29790381 TI - What do TSECs provide in the menopausal hormone therapy? AB - Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45 mg/BZA 20 mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT). In addition, TSEC has shown improvements in quality of life and vaginal atrophy. In respect to MHT using progestins, the benefits of TSEC are found mainly in the bleeding pattern, amenorrhea rate, and reduction in mammary repercussion (i.e., breast tenderness and radiological density). The objective of this guide will be to analyze the efficacy and safety of TSEC consisting of CE/BZA in postmenopausal women. PMID- 29790382 TI - Toward Respiratory-Gated Retrograde Intrarenal Surgery: A Prospective Controlled Randomized Study. AB - INTRODUCTION: We set out to investigate whether general anesthesia with low ventilation (LV, respiratory rate <=8/minute and tidal volume <500 mL) could reduce renal mobility and thereby facilitate improved retrograde intrarenal surgery (RIRS) compared with general anesthesia with standard ventilation (SV). MATERIALS AND METHODS: All 60 consecutive patients who presented for RIRS in our department from September 1, 2017 to December 31, 2017 were prospectively randomized 1:1 into one group that was selected to receive SV and another that received LV. Significant factors influencing the study endpoints considered fragmentation rate (FR), removal rate (RR), processing rate (PR), and operating rate (OR), were statistically analyzed for the whole group as well as for comparison by level of surgeon expertise. RESULTS: Univariate analysis revealed that LV was a significant factor in improving all endpoints. Some endpoints were also affected by the stone's volume, number, and density as well as the surgeon expertise. LV remained the single independent factor for FR, RR, and PR in the multivariate analysis. LV significantly improved all four of the fellows' endpoints (p < 0.05 for each) and positively influenced the expert's RR (p = 0.04), PR (p = 0.02) and OR (p = 0.04). The performance gap between the fellows and the experts narrowed under LV. The end-tidal CO2 was significantly higher in the LV group (50 vs 36 mm Hg; p < 0.0001), however, without any clinical significance. The overall stone-free rate (97%) and complication rate (5%) were not significantly different between the two groups. The patient's anesthesia related safety was not affected by the mode of ventilation as evidenced by no need to convert from LV to SV during the procedures. CONCLUSIONS: LV during RIRS has a significant positive impact on the overall improvement of surgical performance and effectiveness. It does not negatively affect the patient's anesthesia-related safety and may contribute to considerably improving the performance of in-training endourologists. PMID- 29790383 TI - Focal Treatment for Unilateral Prostate Cancer Using High-Intensity Focal Ultrasound: A Comprehensive Study of Pooled Data. AB - BACKGROUND: Focal therapy for prostate cancer (PCa) remains experimental. Aim of the current study is to review available evidence and perform a pooled analysis exploring oncologic and functional results of high intensity focus ultrasound (HIFU) focal therapy for the treatment of unilateral PCa. METHODS: The National Library of Medicine Database was searched for relevant articles. A wide search was performed, including the combination of following words: "HIFU," "prostate," "cancer," and "focal." Overall, 167 articles were reviewed. Of these, seven articles were identified and eligible for the pooled analysis. Data on HIFU hemiablation or focal prostate ablation, oncologic and functional results were pooled from these seven studies that included 366 men with unilateral PCa. RESULTS: In the 366 analyzed cases, mean age was 67 years (95% confidence interval 66-69), and mean preoperative prostate-specific antigen was 6.4 ng/cc (5.5-7.4). Three studies included PCa up to Gleason 7 (3 + 4), three studies did include also Gleason 7 (4 + 3), whereas one study had no limitation in terms of Gleason score. Regarding early complications, low-grade Clavien-Dindo I-II were reported in 26% (16-37), whereas high-grade Clavien-Dindo >=III were found in 3.8% (0-8.6). Analyzing oncologic outcomes mean follow-up was 26 months (23-31): at one year after HIFU, negative biopsy rate for clinically significant PCa was 87% (79-96), whereas salvage treatment-free survival rate was 92% (85-98). Regarding functional outcomes, reported potency rates were 74% (64-84), and continence 96% (91-100), although definitions of potency and continence were not homogenous across studies. CONCLUSIONS: This pooled analysis of the results of focal HIFU treatment of PCa shows promising oncologic and functional outcomes. Well-selected patients may be candidates for such a conservative partial treatment of the gland. Well-designed trials are awaited to compare HIFU focal treatment with current standard of care. PMID- 29790384 TI - Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells? AB - Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14. PMID- 29790385 TI - Kinect4FOG: monitoring and improving mobility in people with Parkinson's using a novel system incorporating the Microsoft Kinect v2. AB - Parkinson's is a neurodegenerative condition associated with several motor symptoms including tremors and slowness of movement. Freezing of gait (FOG); the sensation of one's feet being "glued" to the floor, is one of the most debilitating symptoms associated with advanced Parkinson's. FOG not only contributes to falls and related injuries, but also compromises quality of life as people often avoid engaging in functional daily activities both inside and outside the home. In the current study, we describe a novel system designed to detect FOG and falling in people with Parkinson's (PwP) as well as monitoring and improving their mobility using laser-based visual cues cast by an automated laser system. The system utilizes a RGB-D sensor based on Microsoft Kinect v2 and a laser casting system consisting of two servo motors and an Arduino microcontroller. This system was evaluated by 15 PwP with FOG. Here, we present details of the system along with a summary of feedback provided by PwP. Despite limitations regarding its outdoor use, feedback was very positive in terms of domestic usability and convenience, where 12/15 PwP showed interest in installing and using the system at their homes. Implications for Rehabilitation Providing an automatic and remotely manageable monitoring system for PwP gait analysis and fall detection. Providing an automatic, unobtrusive and dynamic visual cue system for PwP based on laser line projection. Gathering feedback from PwP about the practical usage of the implemented system through focus group events. PMID- 29790386 TI - Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer. AB - Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E1) was the predominant estrogen in premenopausal breast adipose tissue, and E1 and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E2) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E1 (1519 vs. 3244, p < .05) and E2 (404 vs. 889 pmol/kg, p < .05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05-0.07 vs. 0.17; 0.03 0.2, p = .010) and CYP19A1 (0.08; 0.07-0.14 vs. 0.22; 0.09-0.54, p = .025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E1 and E2 concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer. PMID- 29790387 TI - Crosstalk Between Connexin32 and Mitochondrial Apoptotic Signaling Pathway Plays a Pivotal Role in Renal Ischemia Reperfusion-Induced Acute Kidney Injury. AB - AIMS: Perioperative acute kidney injury (AKI) resulting from renal ischemia reperfusion (IR) is not conducive to the postoperative surgical recovery. Our previous study demonstrated that reactive oxygen species (ROS) transmitted by gap junction (GJ) composed of connexin32 (Cx32) contributed to AKI. However, the precise underlying pathophysiologic mechanisms were largely unknown. This study focuses on the underlying mechanisms related to ROS transmitted by Cx32 responsible for AKI aggravation. RESULTS: In a set of in vivo studies, renal IR was found to cause severe impairment in renal tissues with massive ROS generation, which occurred contemporaneously with activation of NF-kappaB/p53/p53 upregulated modulator of apoptosis (PUMA)-mediated mitochondrial apoptosis pathways. Cx32 deficiency alleviated renal IR-induced AKI, and simultaneously attenuated ROS generation and distribution in renal tissues, which further inhibited NF-kappaB/p53/PUMA-mediated mitochondrial apoptotic pathways. Correspondingly, in a set of in vitro studies, hypoxia reoxygenation (HR)-induced cellular injury, and cell apoptosis in both human kidney tubular epithelial cells (HK-2s) and rat kidney tubular epithelial cells (NRK52Es) were significantly attenuated by Cx32 inhibitors or Cx32 gene knockdown. More importantly, Cx32 inhibition not only decreased ROS generation and distribution in human or rat kidney tubular epithelial cells but also inhibited its downstream NF kappaB/p53/PUMA-mediated mitochondrial apoptotic pathway activation. Innovation and Conclusion: This is the first identification of the underlying mechanisms of IR-induced renal injury integrally which demonstrates the critical role played by Cx32 in IR-induced AKI. Moreover, GJ composed of Cx32 manipulates ROS generation and distribution between neighboring cells, and alters activation of NF kappaB/p53/PUMA-mediated mitochondrial apoptotic pathways. Both inhibiting Cx32 function and scavenging ROS effectively reduce mitochondrial apoptosis and subsequently attenuate AKI, providing effective strategies for kidney protection. Antioxid. Redox Signal. 00, 000-000. PMID- 29790388 TI - Graft function assessment in mouse models of single- and dual-kidney transplantation. AB - Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild-type recipients or vice versa. Dual-kidney transplantation (DKT) provides a more physiological environment for recipients than single-kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications, and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher glomerular filtration rate (GFR) than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 ul/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease. PMID- 29790389 TI - Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat. AB - The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 wk) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a nonobese type 2 diabetic model, and nondiabetic Sprague-Dawley rats. In nondiabetic rats, Ipra increased urinary excretion of Na+ (UNaV) and fluid (UV) associated with increased food and fluid intake. Diabetes increased these four parameters, but Ipra had no further effect, probably because of its antihyperglycemic effect, such that glucosuria and, as a consequence, food and fluid intake were unchanged. Fluid balance and BFV, determined by bioimpedance spectroscopy, were similar among the four groups. To study the impact of food and fluid intake, nondiabetic rats were treated for 7 days with Veh, Ipra, or Ipra+pair feeding+pair drinking (Pair-Ipra). Pair-Ipra maintained a small increase in UV and UNaV versus Veh despite similar food and fluid intake. Pair-Ipra induced a negative fluid balance and decreased BFV, whereas Ipra or Veh had no significant effect compared with basal values. In conclusion, SGLT2 inhibition induces a sustained diuretic and natriuretic tone. Homeostatic mechanisms are activated to stabilize BFV, including compensatory increases in fluid and food intake. PMID- 29790390 TI - Collecting duct principal, but not intercalated, cell prorenin receptor regulates renal sodium and water excretion. AB - The collecting duct is the predominant nephron site of prorenin and prorenin receptor (PRR) expression. We previously demonstrated that the collecting duct PRR regulates epithelial Na+ channel (ENaC) activity and water transport; however, which cell type is involved remains unclear. Herein, we examined the effects of principal cell (PC) or intercalated cell (IC) PRR deletion on renal Na+ and water handling. PC or IC PRR knockout (KO) mice were obtained by crossing floxed PRR mice with mice harboring Cre recombinase under the control of the AQP2 or B1 subunit of the H+ ATPase promoters, respectively. PC KO mice had reduced renal medullary ENaC-alpha abundance and increased urinary Na+ losses on a low Na+ diet compared with controls. Conversely, IC KO mice had no apparent differences in Na+ balance or ENaC abundance compared with controls. Acute treatment with prorenin increased ENaC channel number and open probability in acutely isolated cortical collecting ducts from control and IC PRR KO, but not PC PRR KO, mice. Furthermore, compared with controls, PC KO, but not IC KO mice, had increased urine volume, reduced urine osmolality, and reduced abundance of renal medullary AQP2. Taken together, these findings indicate that PC, but not IC, PRR modulates ENaC activity, urinary Na+ excretion, and water transport. PMID- 29790392 TI - Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury. AB - Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Drug induced/toxic AKI can be caused by a number of therapeutic agents. Cisplatin is an effective chemotherapeutic agent whose administration is limited by significant nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. Although tumor necrosis factor-alpha (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the innate immune signaling pathways that trigger TNF generation in this context require elucidation. In this regard, sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1alpha and IL-1beta. In turn, stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a proinflammatory signaling cascade that induces TNF induction. We therefore hypothesized that IL 1R1 activation exacerbates cisplatin-induced AKI by inducing TNF production, thereby augmenting inflammatory signals between kidney parenchymal cells and infiltrating myeloid cells. IL-1R1+/+ (WT) and IL-1R1-/- (KO) mice were subjected to cisplatin-induced AKI. Compared with WT mice, IL-1R1 KO mice had attenuated AKI as measured by serum creatinine and BUN, renal NGAL mRNA levels, and blinded histological analysis of kidney pathology. In the cisplatin-injured kidney, IL 1R1 KO mice had diminished levels of whole kidney TNF, and fewer Ly6G-expressing neutrophils. In addition, an unbiased machine learning analysis of intrarenal immune cells revealed a diminished number of CD11bint/CD11cint myeloid cells in IL-1R1 KO injured kidneys compared with IL-1R1 WT kidneys. Following cisplatin, IL-1R1 KO kidneys, compared with WTs, had fewer TNF-producing: macrophages, CD11bint/CD11cint cells, and neutrophils, consistent with an effect of IL-1R1 to polarize intrarenal myeloid cells toward a proinflammatory phenotype. Interruption of IL-1-dependent signaling pathways warrants further evaluation to decrease nephrotoxicity during cisplatin therapy. PMID- 29790391 TI - Neutrophil exocytosis induces podocyte cytoskeletal reorganization and proteinuria in experimental glomerulonephritis. AB - Acute glomerulonephritis is characterized by rapid glomerular neutrophil recruitment, proteinuria, and glomerular hypercellularity. The current study tested the hypothesis that the release of neutrophil granule contents plays a role in both the loss of filtration barrier leading to proteinuria and the increase in glomerular cells. Inhibition of neutrophil exocytosis with a peptide inhibitor prevented proteinuria and attenuated podocyte and endothelial cell injury but had no effect on glomerular hypercellularity in an experimental acute glomerulonephritis model in mice. Cultivation of podocytes with neutrophil granule contents disrupted cytoskeletal organization, an in vitro model for podocyte effacement and loss of filtration barrier. Activated, cultured podocytes released cytokines that stimulated neutrophil chemotaxis, primed respiratory burst activity, and stimulated neutrophil exocytosis. We conclude that crosstalk between podocytes and neutrophils contributes to disruption of the glomerular filtration barrier in acute glomerulonephritis. Neutrophil granule products induce podocyte injury but do not participate in the proliferative response of intrinsic glomerular cells. PMID- 29790394 TI - Speech and language pathologists' perceptions and practises of communication partner training to support children's communication with high-tech speech generating devices. AB - PURPOSE: This study examined speech and language pathologists' (SLPs') perceptions and practices of communication partner training with high-tech speech generating devices (SGDs). METHOD: Fifteen SLPs were recruited throughout Sweden. The SLPs answered a study-specific questionnaire on communication partner training in relation to communication partners to children with severe cerebral palsy and intellectual disability. The results were analysed with descriptive statistics (closed-ended questions, responses on Likert scales) and content analysis (open-ended question) using ICF-CY. RESULTS: Twelve SLPs completed the survey. Half had no or one training session with communication partners in the last year. One-third never used documents for goal-setting. Half seldom or never taught communication partner strategies. Three quarters only used verbal instructions. The main obstacles were environmental factors. CONCLUSIONS: This study contributes valuable knowledge about high-tech SGD interventions targeting communication partners. The high-tech SGD intervention may benefit from goal setting, extended number of training sessions and a range of instructional approaches. Implications for Rehabilitation Speech and language pathologist (SLPs) reported that children with severe cerebral palsy and intellectual disability (SSPI) can benefit from speech generating device (SGD) communication. Communication partner strategies and goal-setting supports the development of communication with SGD. SLPs seldom taught stakeholder communication partner strategies and instruments for goal-setting. Because stakeholders may vary in their way of learning SLPs need to use a variety of instructional approaches. SLPs used few instructional approaches, typically verbal information. PMID- 29790395 TI - Hyaluronic acid-conjugated pH-sensitive liposomes for targeted delivery of prednisolone on rheumatoid arthritis therapy. AB - AIM: The treatment of rheumatoid arthritis remains a challenge as available therapies still entail the risk of deleterious off-target effects. The present study describes hyaluronic acid-conjugated pH-sensitive liposomes as an effective drug delivery-targeting strategy to synovial cells. MATERIALS & METHODS: Therapeutic, cytotoxic and targeting potential of developed liposomes were studied in vitro using macrophages and fibroblasts cell lines. RESULTS & CONCLUSION: Results suggest an enhanced cellular uptake of conjugated liposomes, mainly mediated by caveolae- and clathrin-dependent endocytosis. In vitro release studies demonstrated that prednisolone was preferentially released under acidic conditions mimicking intracellular endosomal compartments. Overall, results revealed that conjugated pH-sensitive liposomes are a promising nanoapproach for the targeted delivery of prednisolone within inflamed synovial cells for rheumatoid arthritis treatment. PMID- 29790393 TI - Assistive technology policy: a position paper from the first global research, innovation, and education on assistive technology (GREAT) summit. AB - Increased awareness, interest and use of assistive technology (AT) presents substantial opportunities for many citizens to become, or continue being, meaningful participants in society. However, there is a significant shortfall between the need for and provision of AT, and this is patterned by a range of social, demographic and structural factors. To seize the opportunity that assistive technology offers, regional, national and sub-national assistive technology policies are urgently required. This paper was developed for and through discussion at the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit; organized under the auspices of the World Health Organization's Global Collaboration on Assistive Technology (GATE) program. It outlines some of the key principles that AT polices should address and recognizes that AT policy should be tailored to the realities of the contexts and resources available. AT policy should be developed as a part of the evolution of related policy across a number of different sectors and should have clear and direct links to AT as mediators and moderators for achieving the Sustainable Development Goals. The consultation process, development and implementation of policy should be fully inclusive of AT users, and their representative organizations, be across the lifespan, and imbued with a strong systems-thinking ethos. Six barriers are identified which funnel and diminish access to AT and are addressed systematically within this paper. We illustrate an example of good practice through a case study of AT services in Norway, and we note the challenges experienced in less well-resourced settings. A number of economic factors relating to AT and economic arguments for promoting AT use are also discussed. To address policy-development the importance of active citizenship and advocacy, the need to find mechanisms to scale up good community practices to a higher level, and the importance of political engagement for the policy process, are highlighted. Policy should be evidence-informed and allowed for evidence-making; however, it is important to account for other factors within the given context in order for policy to be practical, authentic and actionable. Implications for Rehabilitation The development of policy in the area of asssitive technology is important to provide an overarching vision and outline resourcing priorities. This paper identifies some of the key themes that should be addressed when developing or revising assistive technology policy. Each country should establish a National Assistive Technology policy and develop a theory of change for its implementation. PMID- 29790396 TI - Biosensor for the detection of Listeria monocytogenes: emerging trends. AB - The early detection of Listeria monocytogenes (L. monocytogenes) and understanding the disease burden is of paramount interest. The failure to detect pathogenic bacteria in the food industry may have terrible consequences, and poses deleterious effects on human health. Therefore, integration of methods to detect and trace the route of pathogens along the entire food supply network might facilitate elucidation of the main contamination sources. Recent research interest has been oriented towards the development of rapid and affordable pathogen detection tools/techniques. An innovative and new approach like biosensors has been quite promising in revealing the foodborne pathogens. In spite of the existing knowledge, advanced research is still needed to substantiate the expeditious nature and sensitivity of biosensors for rapid and in situ analysis of foodborne pathogens. This review summarizes recent developments in optical, piezoelectric, cell-based, and electrochemical biosensors for Listeria sp. detection in clinical diagnostics, food analysis, and environmental monitoring, and also lists their drawbacks and advantages. PMID- 29790398 TI - Acute Inflammatory Biomarker Responses to Diffuse Traumatic Brain Injury in the Rat Monitored by a Novel Microdialysis Technique. AB - Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial cerebrospinal fluid (CSF) to optimize protein capture. Six hourly samples were analyzed for 27 inflammatory biomarkers (9 chemokines, 13 cytokines, and 5 growth factors) using a commercial multiplex biomarker kit. TBI (n = 6) resulted in a significant increase compared with sham-injured controls (n = 6) for five chemokines (eotaxin/CCL11, fractalkine/CX3CL1, LIX/CXCL5, monocyte chemoattractant protein [MCP]1alpha/CCL2, macrophage inflammatory protein [MIP]1alpha /CCL3), 10 cytokines (interleukin [IL]-1alpha, IL-1beta, IL-4, IL-6, IL-10, IL-13, IL-17alpha, IL-18, interferon [IFN]-gamma, tumor necrosis factor [TNF]-alpha), and four growth factors (epidermal growth factor [EGF], granulocyte macrophage colony-stimulating factor [GM-CSF], leptin, vascular endothelial growth factor [VEGF]). Therefore, diffuse TBI was associated with an increased level of 18 of the 27 inflammatory biomarkers at one through six time points, during the observation period whereas the remaining 9 biomarkers were unaltered. The study shows that diffuse TBI induces an acute increase in a number of inflammatory biomarkers. The novel MD technique provides stable MD sampling suitable for further studies on the early neuroinflammatory cascade in TBI. PMID- 29790397 TI - Higher cartilage wear in unipolar than bipolar hemiarthroplasties of the hip at 2 years: A randomized controlled radiostereometric study in 19 fit elderly patients with femoral neck fractures. AB - Background and purpose - The use of unipolar hemi-arthroplasties for femoral neck fractures is increasing in some countries due to reports of higher reoperation rates in bipolar prostheses. On the other hand, it has been proposed that bipolar hemiarthroplasties have clinical advantages and less cartilage wear than unipolar hemiarthroplasties. We compared cartilage wear between bipolar and unipolar hemiarthroplasties using radiostereometric analyses (RSA), in patients aged 70 years or older. Patients and methods - 28 ambulatory, lucid patients were randomized to treatment with a unipolar or a bipolar hemiarthroplasty for an acute femoral neck fracture. Migration of the prosthetic head into the acetabulum was measured using RSA. Secondary outcomes were Harris Hip Score (HHS), and EQ-5D scores. Patients were assessed at 3, 12. and 24 months. Results - 19 patients were available for follow-up at 2 years: mean proximal penetration was 0.83 mm in the unipolar group and 0.24 mm in the bipolar group (p = 0.01). Mean total point movement was 1.3 mm in the unipolar group and 0.95 mm in the bipolar group (p = 0.3). Median HHS was 78 (62-96) in the unipolar group and 100 (70-100) in the bipolar group (p = 0.004). Median EQ-5D Index Score was 0.73 (0.52-1.00) in the unipolar group and 1.00 (0.74-1.00) in the bipolar group (p = 0.01). Median EQ-5D VAS was 70 (50-90) in the unipolar group and 89 (70-95) in the bipolar group (p = 0.03) Interpretation - Patients with unipolar hemiarthroplasties had higher proximal cartilage wear and lower functional outcomes. Unipolar hemiarthroplasties should be used with caution in ambulatory, lucid patients. PMID- 29790399 TI - Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides. AB - An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment. PMID- 29790400 TI - The activity of silver nanoparticles against microalgae of the Prototheca genus. AB - AIM: To investigate the in vitro activity of silver NPs (AgNPs) against pathogenic microalgae of the Prototheca genus. MATERIALS & METHODS: The antialgal potential of AgNPs against Prototheca species of both clinical and environmental origin was assessed from minimum inhibitory (algistatic) and algicidal concentrations. The in vitro cytotoxicity of AgNPs against bovine mammary epithelial cell line was evaluated by means of the standard MTT assay. RESULTS: AgNPs showed a strong killing activity toward Prototheca algae, as the minimal algicidal concentration (MAC) values matched perfectly the corresponding minimum inhibitory concentration (MIC) values for all species (MAC = MIC, 1-4 mg/l), except P. stagnora (MIC > 8 mg/l). The concentrations inhibitory to pathogenic Prototheca spp. (MIC, 1-4 mg/l) were below the concentrations at which any toxicity in epithelial cells could be observed (CC20 > 6 mg/l). CONCLUSION: The study emphasizes the potential of AgNPs as a new therapeutic tool for the management of Prototheca infections. PMID- 29790401 TI - Translational gaps in animal models of human infusion reactions to nanomedicines. AB - Adverse infusion reactions to regulatory approved nanomedicines in human subjects are idiosyncratic, but outwardly reproducible in pigs. A large body of evidence suggests that the porcine reactions are related to robust nanoparticle clearance by pulmonary intravascular macrophages (PIMs), and rapid release of arachidonate metabolites from these cells. Similar to pigs, other animals that have resident PIMs in their lungs also respond to intravenously injected particles, where rapid particle clearance by PIMs correlate with peak periods of cardiopulmonary distress. Normal human lungs, however, do not have PIMs, but 'induced' PIMs have been identified in pulmonary circulation under certain pathological conditions. We question suitability, and limitation of these preclinical models for global assessment of nanomedicine safety, and discuss alternative models and approaches. PMID- 29790402 TI - Vitamin D pathway gene polymorphisms affecting daclatasvir plasma concentration at 2 weeks and 1 month of therapy. AB - AIM: Vitamin D (VD) influences genetic expression through its receptor (VDR). VD pathway gene polymorphisms seem to influence antiviral drug pharmacokinetics and therapeutic outcome/toxicity. We investigated the association between daclatasvir (DCV) plasma concentrations and genetic variants (SNPs) associated with the VD pathway. PATIENTS & METHODS: Chronic hepatitis C patients treated with DCV from 2014 to 2016 were included. Genotypes were assessed through real-time PCR and plasma concentrations through liquid chromatography. RESULTS: A total of 52 patients were analyzed. DCV levels were influenced by CYP24A1 rs2248359T>C polymorphism at 2 weeks and VDR Cdx2 A>G at 1 month of treatment. Linear regression analysis showed baseline BMI, alanine aminotransferase and hematocrit as significant predictors of DCV concentrations at 2 weeks, BMI and hematocrit at baseline, VDR Cdx2 AG/GG and FokI TC/CC at 1 month. CONCLUSION: These results showed a possible role of VD pathway gene polymorphisms in influencing DCV plasma concentrations, but further studies are required. PMID- 29790403 TI - The Amelioration of Pain-Related Behavior in Mice with Chronic Spinal Cord Injury Treated with Neural Stem/Progenitor Cell Transplantation Combined with Treadmill Training. AB - Progress in regenerative medicine is realizing the possibility of neural regeneration and functional recovery in spinal cord injury (SCI). Recently, rehabilitation has attracted much attention with respect to the synergistic promotion of functional recovery in combination with neural stem/progenitor cell (NS/PC) transplantation, even in the chronic refractory phase of SCI. Nevertheless, sensory disturbance is one of the most prominent sequelae, even though the effects of combination or single therapies have been investigated mostly in the context of motor recovery. To determine how combination therapy with treadmill training (TMT) and NS/PC transplantation affects the manifestation of thermal allodynia and tactile hyperalgesia in chronic phase SCI, four groups of SCI mice were used to assess pain-related behavior and histological changes: combined transplantation and TMT therapy, transplantation only, TMT only, and control groups. Thermal allodynia and coarse touch-pressure hyperalgesia exhibited significant recovery in the combined therapy group in comparison with controls, whereas there were no significant differences with fine touch-pressure hyperalgesia and motor function. Further investigation revealed fewer fibers remaining in the posterior funiculus, which contained the tracts associated with the two modalities showing less recovery; that is, touch-pressure hyperalgesia and motor function. A significant correlation was only observed between these two modalities. Although no remarkable histological recovery was found within the lesion epicenter, changes indicating amelioration of pain were observed in the lumbar enlargement of the combination therapy group. Our results suggest that amelioration of thermal allodynia and tactile hyperalgesia can be brought about by the additive effect of NS/PC transplantation and TMT. The degree of recovery seems dependent on the distribution of damage. PMID- 29790404 TI - Clinical and Neurophysiological Changes after Targeted Intrathecal Injections of Bone Marrow Stem Cells in a C3 Tetraplegic Subject. AB - High-level quadriplegia is a devastating condition with limited treatment options. Bone marrow derived stem cells (BMSCs) are reported to have immunomodulatory and neurotrophic effects in spinal cord injury (SCI). We report a subject with complete C2 SCI who received three anatomically targeted intrathecal infusions of BMSCs under a single-patient expanded access investigational new drug (IND). She underwent intensive physical therapy and was followed for >2 years. At end-point, her American Spinal Injury Association Impairment Scale (AIS) grade improved from A to B, and she recovered focal pressure touch sensation over several body areas. We conducted serial neurophysiological testing to monitor changes in residual connectivity. Motor, sensory, and autonomic system testing included motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), electromyography (EMG) recordings, F waves, galvanic skin responses, and tilt-table responses. The quality and magnitude of voluntary EMG activations increased over time, but remained below the threshold of clinically obvious movement. Unexpectedly, at 14 months post injury, deep inspiratory maneuvers triggered respiratory-like EMG bursting in the biceps and several other muscles. This finding means that connections between respiratory neurons and motor neurons were newly established, or unmasked. We also report serial analysis of MRI, International Standards for Neurological Classification of SCI (ISNCSCI), pulmonary function, pain scores, cerebrospinal fluid (CSF) cytokines, and bladder assessment. As a single case, the linkage of the clinical and neurophysiological changes to either natural history or to the BMSC infusions cannot be resolved. Nevertheless, such detailed neurophysiological assessment of high cervical SCI patients is rarely performed. Our findings indicate that electrophysiology studies are sensitive to define both residual connectivity and new plasticity. PMID- 29790405 TI - Poor medication adherence in patients with psoriasis and a successful intervention. AB - BACKGROUND: The medication adherence of psoriasis patients may be influenced by a series combined internal and external factors. Effective methods for improving adherence could improve treatment outcomes. OBJECTIVE: To characterize medication adherence in psoriasis patients in China and to test an intervention to improve psoriasis patients' adherence. METHODS: We investigated 200 patients with psoriasis using questionnaires to determine their medication adherence and the factors that influence adherence. In 117 patients, low medication adherence were identified; we randomized 96 of these patients into intervention group and control groups. The intervention group received health education during six months therapy. One-way Analysis of Variance (one-way ANOVA) was used to analyze the influence factors of medication adherence to further obtain the variables. Logistic regression was used to analyze these data. RESULTS: Adherence of psoriasis patients was poor (41.5%). Factors associated with adherence included sociological characteristics, disease characteristics, medicine type, the cognitive level toward psoriasis, care indicators, and social environment. Patients in the intervention group exhibited greater adherence improvement (83.7%) compared with the control group (6.4%). CONCLUSION: Medication adherence of the psoriasis patients is poor but can be improved by a health education intervention. PMID- 29790406 TI - Highlights from the latest in nanomedicine research. PMID- 29790408 TI - Working Men's Constructions of Visiting the Doctor. AB - To understand influences on medical help seeking in men from traditionally masculine occupations, semistructured interviews with 12 men employed in manual and industrial labor were conducted. The semistructured interview format explored participant men's understanding and experiences of annual exams and medical help seeking, their own and others' reactions to seeking medical help, and influences on their own care and understanding of what it means to seek medical care. Utilizing consensual qualitative research methodology, five domains emerged: Social norms around medical care, managing threat, getting medical help is gendered, work-related influences, and pragmatic contributors to medical help seeking. Results extended the literature by situating men's understanding of physician visits within a gendered and social context, and highlighting the influence of work and coworkers, where messages are often contradictory and inconsistent about medical help seeking. Future research should examine additional contextual factors influencing men's attitudes toward seeking health care, including race, culture, and sexual orientation, as well as seek to develop and evaluate interventions that promote men's utilization of medical services. PMID- 29790407 TI - Age Cohort and Health Service Utilization Among Gay Men. AB - Gay men report unique health disparities and service utilization trends compared to their heterosexual peers including a lack of health-care participation which may lead to chronic health conditions. Limited research has been conducted analyzing group differences among gay men such as the influence of one's age cohort on disparities. The aim of this study was to examine the association age cohort has on health service utilization among gay men. A sample of 383 self identified gay men was collected by the San Francisco Department of Public Health. Older men were less likely to have visited a medical provider in the past 12 months compared to middle-aged men (OR = 0.10; 95% CI [2.47, 39.8]) and younger men (OR = 0.35; 95% CI [1.28, 10.42]). However, older men were more likely to have a usual source of medical care compared to younger men (OR = 4.0; 95% CI [.05, .84]). Age cohort differences in health-care service utilization appear to exist among gay men. This study highlights additional areas for exploration including the impact HIV and socioeconomic status have on health seeking behavior and health service utilization. PMID- 29790410 TI - Perspectives on Electronic Informed Consent From Patients Underrepresented in Research in the United States: A Focus Group Study. AB - Digital informed consent may better inform individuals about health research and increase participation. In the United States and elsewhere, minorities and rural populations are underrepresented in health research and may benefit from well designed electronic informed consent (eIC). Seven focus groups were conducted with 50 Caucasian, African American, and rural patients in the United States. Participants were asked their preferences for a paper versus electronic informed consent document. Participants found the e-version easier to use, more interesting, and better for understanding. Minority participants emphasized limited access, computer literacy, and trust barriers to eIC. Rural participants were concerned about accessibility, connectivity, privacy, and confidentiality. People see value in electronic consenting. Researchers should consider barriers to eIC among underrepresented populations before recruitment. PMID- 29790409 TI - Postural Stability and Physical Activity of Workers Working at Height. AB - The purpose of the study was to analyze the level of postural stability and physical activity of at-height workers. The study included 34 healthy men aged 25 43. Two groups were identified based on the type of work they performed: at height workers (HW) ( n = 17), and office workers (OW) ( n = 17). Physical activity, including physical activity at work, sports activity, and leisure, was assessed with a Baecke questionnaire. For evaluation of postural stability, the one-leg standing test with eyes open and closed was used. The HW group had a higher rate of average physical activity at work than the OW group ( p = .000), whereas the OW group showed greater physical activity during leisure time ( p = .000). No differences were found between the groups in terms of sports activity. Postural stability analysis shows that the HW group ( p < .05) scored statistically significantly higher values in one-leg standing with eyes closed. The groups differed in terms of postural stability in favor of HW. At the same time, despite differences in particular aspects, the overall level of PA was similar. This may indicate that postural stability is rather affected by exposure to distress conditions. PMID- 29790411 TI - Genetic and Environmental Influences on Achievement Outcomes Based on Family History of Learning Disabilities Status. AB - A risk to develop a learning disability has been shown to run in families. Having a positive family history of learning disability seems to account for mean differences in achievement outcomes (reading, math) in that children with a positive family history score significantly lower compared to their peers with no such family history. However, the role of family history status in explaining etiological (genetic and environmental) differences among these subgroups of children has yet to be established. The present study of 872 twins ( Mage = 13.30, SDage = 1.40) from the Florida Twin Project on Reading, Behavior, and Environment utilized a multigroup approach to examine etiological differences on reading, spelling, and math among two subgroups defined by family history status. Results showed significant mean differences on all achievement outcomes, aside from math; however, no significant etiological differences on any achievement outcome were found among the two subgroups. Results support previous literature that the risk for developing a learning disability is transmitted through a family, but this is seemingly not manifested by differential etiology. PMID- 29790412 TI - Career and Technical Education, Inclusion, and Postsecondary Outcomes for Students With Learning Disabilities. AB - We used longitudinal data from Washington State to investigate the relationships among career and technical education (CTE) enrollment, inclusion in general education, and high school and postsecondary outcomes for students with learning disabilities. We replicated earlier findings that students with learning disabilities who were enrolled in a "concentration" of CTE courses had higher rates of employment after graduation than observably similar students with learning disabilities who were enrolled in fewer CTE courses. We also found that students with learning disabilities who spent more time in general education classrooms in high school had higher rates of on-time graduation, college attendance, and employment than observably similar students with learning disabilities who spent less time in general education classrooms in these grades. PMID- 29790413 TI - Specific Language Impairment and Reading Disability: Categorical Distinction or Continuum? AB - Specific language impairment (SLI) and reading disability (RD) are familial, moderately heritable comorbid developmental disorders. The key deficit of SLI is oral language, whereas children with RD exhibit impairment in learning to read. The present study examines the possible co-occurrence of RD and SLI and the nature of this co-occurrence at a linguistic and a cognitive level in an orthographically consistent language. Four groups of children participated in the study: an RD group ( n = 10), an SLI group ( n = 13), a possible comorbid group ( n = 9), and a control-no deficit group ( n = 20). Analysis showed that all three clinical groups in our sample performed similarly in phonological awareness and naming-speed tasks. However, significant group differences were observed in orthographic processing, reading, semantics, and phonological memory measures, thus supporting the view that SLI and RD are distinct disorders. Results are in line with previous findings indicating that SLI and RD share common characteristics, although the two conditions are manifested with different symptoms. PMID- 29790414 TI - Pharmacogenomics in liver transplantation: testing the recipient and the ex-vivo donor liver. PMID- 29790415 TI - A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT. AB - AIM: To determine the influence of polymorphisms on the effects of metformin on HbA1c, daily dose of insulin and metformin plasma concentration. Methods: In a post hoc analysis of a 4.3 year placebo-controlled randomized trial with 390 patients with Type 2 diabetes already on insulin, we analyzed the influence of polymorphisms in genes coding for ATM and the transporters OCT1 and MATE1. Outcome measures were a combined HbA1c + daily dose of insulin Z score and metformin plasma concentrations. RESULTS: rs11212617 (ATM) was associated with an improved Z score and a lower metformin plasma concentration. In addition, the major allele of rs2289669 (MATE1) was also associated with an improved Z score. CONCLUSION: The ATM SNP rs11212617 significantly affected the effect of metformin and metformin plasma concentration. Further research is needed to determine the clinical importance of these findings, in particular the effects on metformin plasma concentration. PMID- 29790416 TI - Interpretation bias and social anxiety: does interpretation bias mediate the relationship between trait social anxiety and state anxiety responses? AB - Two studies aimed to examine whether high socially anxious individuals are more likely to negatively interpret ambiguous social scenarios and facial expressions compared to low socially anxious individuals. We also examined whether interpretation bias serves as a mediator of the relationship between trait social anxiety and state anxiety responses, in particular current state anxiety, bodily sensations, and perceived probability and cost of negative evaluation pertaining to a speech task. Study 1 used ambiguous social scenarios and Study 2 used ambiguous facial expressions as stimuli to objectively assess interpretation bias. Undergraduate students with high and low social anxiety completed measures of state anxiety responses at three time points: baseline, after the interpretation bias task, and after the preparation for an impromptu speech. Results showed that high socially anxious individuals were more likely to endorse threat interpretations for ambiguous social scenarios and to interpret ambiguous faces as negative than low socially anxious individuals. Furthermore, negative interpretations mediated the relationship between trait social anxiety and perceived probability of negative evaluation pertaining to the speech task in Study 1 but not Study 2. The present studies provide new insight into the role of interpretation bias in social anxiety. PMID- 29790417 TI - Systematic evaluation of clinical practice guidelines for pharmacogenomics. AB - AIM: To systematically assess methodological quality of pharmacogenomics clinical practice guidelines. METHODS: Guidelines published through 2017 were reviewed by at least three independent reviewers using the AGREE II instrument, which consists of 23 items grouped into 6 domains and 2 items representing an overall assessment. Items were assessed on a seven-point rating scale, and aggregate quality scores were calculated. RESULTS: 31 articles were included. All guidelines were published as peer-reviewed articles and 90% (n = 28) were endorsed by professional organizations. Mean AGREE II domain scores (maximum score 100%) ranged from 46.6 +/- 11.5% ('applicability') to 78.9 +/- 11.4% ('clarity of presentation'). Median overall quality score was 72.2% (IQR: 61.1 77.8%). CONCLUSION: Quality of pharmacogenomics guidelines was generally high, but variable, for most AGREE II domains. PMID- 29790419 TI - RICTOR gene amplification is correlated with metastasis and therapeutic resistance in triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) is characterized by its aggressive behavior, metastasis and lack of targeted therapies. Herein, we discuss the clinical, histopathological and genetic profile of a woman diagnosed with TNBC. Since the patient had no durable response to chemotherapy, a genetic profiling was carried out. Next-generation sequencing analysis of 592 genes showed a missense mutation, p.E545A in PIK3CA, thus the patient was started on the mTOR inhibitor everolimus, in combination with exemestane, which controlled her pain; however, the disease progressed aggressively. More importantly, next-generation sequencing analysis showed a RICTOR gene amplification (eight copies) suggesting that RICTOR promotes the genesis of TNBC. We conclude that determining regulators of RICTOR and furthermore, their inhibitors might decrease cancer cells proliferation rate in patients with TNBC. PMID- 29790418 TI - Enhanced brain penetration of pretomanid by intranasal administration of an oil in-water nanoemulsion. AB - AIM: To enhance the drug delivery to the brain with an oil-in-water nanoemulsion of pretomanid via intranasal (IN) administration. MATERIALS & METHODS: The study involved 70 male Sprague-Dawley rats (160-180 g) that received either 20 mg/kg body weight (b.w.) a nanoemulsion or a 20 mg/kg b.w. of pretomanid in solution via the IN route. The drug was quantified by liquid chromatography-tandem mass spectrometry to investigate whole tissue-drug concentrations, and mass spectrometric imaging to visualize drug localization in the brain. RESULTS: Nanoemulsion delivery concentrations of pretomanid in the brain reached peak concentrations (Cmax) of 12,062.3 ng/g that is significantly higher than the required therapeutic level. The mass spectrometric imaging analysis clearly showed a time dependent and uniform distribution in the brain. CONCLUSION: The results of this study show that IN delivery of oil-in-water nanoemulsion may be very promising for targeting anatomical tuberculosis reservoirs, such as the brain. PMID- 29790420 TI - Olfactory Training in Post-Traumatic Smell Impairment: Mild Improvement in Threshold Performances: Results from a Randomized Controlled Trial. AB - Traumatic Brain Injury (TBI) can be associated with partial or total smell loss. Recent studies have suggested that olfactory outcome can be positively modulated after olfactory training (OT). This study's aim was to investigate OT's potential role in smell recovery after TBI-induced olfactory loss. A prospective, randomized, and controlled study was developed. Patients with TBI-induced olfactory dysfunction (n = 42) were randomized into an experimental group with OT and a control group without (nOT). OT was performed twice daily with a six odor training set during 12 weeks. Olfactory loss was assessed using subjective olfactometry (Barcelona Smell Test [BAST] 24), a visual analogue scale (VAS), and n-butanol threshold (n-BTt) at baseline at 4, 12, and 24 weeks. Additionally, patients underwent MRI of the olfactory brain and olfactory bulbs (OB). Based on the MRI results, an overall score (0-16) was developed to associate the structural neurological damage with olfactory outcomes. The primary outcome was the change in olfactory measurements (VAS and BAST-24) between baseline and 12 weeks. The secondary outcome was the association of the MRI score with olfactory outcomes at baseline, and the impact on quality of life (QoL). After 12 weeks of training, OT patients showed a significant improvement in n-BTt (0.6 +/- 1.7 OT vs. -0.6 +/- 1.8 nOT, p < 0.05), but not in the smell VAS and BAST-24 scores. Olfactory outcomes (VAS, BAST-24, and n-BTt) were significantly associated with MRI structural findings (p < 0.001), but not with the OB volume or olfactory sulcus length. The present study suggests that 12 weeks of OT mildly improves the olfactory threshold in TBI, whereas the overall MRI score may be used as an imaging marker of olfactory dysfunction and disease severity in TBI patients. PMID- 29790422 TI - Autologous Induced Pluripotent Stem Cell-Derived Neurons to Treat Parkinson's Disease. AB - In 2012, we planned a program to develop a neuron replacement therapy for Parkinson's disease (PD) that would have the greatest promise to help the patients. PD is a movement disorder caused by the progressive, inevitable loss of a specific type of dopamine neuron in the brain. The only viable treatment to reverse the progress of the disease is to replace those neurons; we decided to make dopamine neurons that matched the patients, by differentiating induced pluripotent stem cells that we generated from individuals with PD. This autologous cell therapy is entering the regulatory approval process this year with the U.S. Food and Drug Administration to begin to transplant the cells in the following 1 to 2 years. PMID- 29790421 TI - Facilitators and Barriers to Oncologists' Conduct of Goals of Care Conversations. AB - INTRODUCTION: Goals of care (GoC) conversations optimally begin early in the course of cancer care, yet most happen near the end of life. We sought to describe oncologist-reported facilitators of and barriers to GoC conversations with patients who have advanced cancer. METHODS AND MATERIALS: We conducted individual, semistructured qualitative interviews with oncologists from 4 academic, community, municipal, and rural hospitals in New York and Connecticut. Interview topics included approach to GoC conversations, facilitators, barriers, and organizational influences. We analyzed data using interpretive description. We collected demographic and practice information and surveyed oncologists on their communication skills training. We calculated descriptive statistics for quantitative data. RESULTS: Oncologists (n = 21) had a mean age of 46 years (range: 34-68), 67% were male, 71% were White, 24% were Asian, 10% were Hispanic, and 5% were Black. They reported an average of 20 years in practice (range: 8 42), and 62% had received training on having GoC conversations. Facilitators included patient's poor functional status, patient's high health literacy, family understanding and acceptance, oncologist's practice experience, and a supportive practice environment. Barriers included certain patient demographic and clinical characteristics, patient religion and culture, patient's denial, and lack of time. CONCLUSION: GoC conversations may be facilitated by enabling oncologists to conduct these conversations despite difficult circumstances and emotional reactions by activating patients and family via increased health literacy and by advancing palliative-informed practice environments. PMID- 29790423 TI - Improved Cost-Effectiveness and Blood Product Utilization From Instituting a Blood Ordering Algorithm for Cardiac Surgical Cases. AB - BACKGROUND: Results of a previous study revealed an over-ordering of blood products for cardiac surgery and led to the creation of a new blood ordering algorithm. This follow-up study has been conducted to evaluate improvement in ordering practices. METHODS: Retrospective data were collected for 171 patients who underwent coronary artery bypass grafting or valve surgery from March 2015 to March 2016 to determine the crossmatch-to-transfusion ratio (C:tx) and potential cost savings. Results were compared with pre-algorithm values and considered statistically significant if the 95% confidence interval did not include zero. RESULTS: Prior to the algorithm, 100% of patients undergoing cardiac surgery were crossmatched. After instituting the algorithm, this decreased to 15%. The overall C:tx decreased from 7.97 to 2.14. Cost savings were calculated as $114.79 (coronary artery bypass grafting) and $129.05 (valve surgery) per patient. CONCLUSIONS: The creation of a new algorithm to guide ordering practices has significantly improved the C:tx, reduced unnecessary crossmatching, and lowered costs. PMID- 29790425 TI - Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats. AB - OBJECTIVE: Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning (HPC) was previously demonstrated to provide neuroprotection and brain recovery from either acute or chronic neurodegeneration in several cellular and animal models. Therefore, the present study was designed to investigate the protective effects of hypoxic preconditioning on apoptosis caused by propofol in neonatal rats. METHODS: Propofol (100 mg/kg) was given to 7-day-old (P7) Sprague Dawley pups. Before the propofol injection, hypoxic preconditioning was administered by subjecting rats to five cycles of 10 min of hypoxia (8% O2) and 10 min of normoxia (21% O2), then 2 h of room air. We detected neuronal structure changes and apoptosis by hematoxylin and eosin (HE) staining and TUNEL assay, respectively. Bcl-2, Bax and cleaved-caspase-3 levels were quantified using Western blotting and immunohistochemistry. RESULT: After treatment with propofol, Bcl-2 levels decreased and Bax and cleaved-caspase-3 levels increased. However, our results suggest that hypoxic preconditioning could reverse this change. Conclusion: Our results indicate that pretreatment with hypoxic preconditioning prevents propofol induced neuroapoptosis by increasing the levels of Bcl-2 and decreasing the levels of Bax and cleaved-caspase-3. PMID- 29790424 TI - The Fate of Autologous Endometrial Mesenchymal Stromal Cells After Application in the Healthy Equine Uterus. AB - Because of their distinct differentiation, immunomodulatory, and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded, and fluorescence labeled in culture. Phosphate-buffered saline (PBS) or MSCs (15 * 106) were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion. The inflammatory response to cell infusion was monitored in endometrial cytology samples. MSCs were detected in endometrial sections at 6, 12, and 24 h, but not later (7 or 14 days), after cell infusion. Cells were in all cases located in the uterine lumen, never within the endometrial tissue. No fluorescence signal was detected in blood samples at any time point after infusion. Cytology analyses showed an increase in % of polymorphonuclear neutrophils between 1 and 3 h after uterine infusion with either MSCs or PBS and a further increase by 6 h only in mares infused with PBS. In summary, endometrial MSCs were detected in the uterine lumen for up to 24 h after infusion, but did not migrate into the healthy endometrium. Moreover, MSCs effectively attenuated the inflammatory response to uterine infusion. We conclude that endometrial MSCs obtained from routine uterine biopsies could provide a safe and effective cell source for treatment of inflammatory conditions of the uterus and potentially other tissues. PMID- 29790426 TI - Long-Term Effects of Simulated Microgravity and Vibration Exposure on Skeletal Development in Zebrafish. AB - Most studies utilizing fish to study the effects of simulated microgravity (SMG) only observe the effects during the first week of development. They also do not take into account the potential impact on development of vibrations caused by the equipment. In this study we analyze the effects of both SMG and vibration on development of the skeleton. We analyze three different exposure durations and starting points that coincide with cranial neural crest cell migration. We use a combination of bone staining and morphometrics to analyze the effects. Our data show that both vibration and SMG affect vertebra number and body size; however, not all vertebrae are equally affected by each treatment. We also show that delayed ossification manifests during development, particularly after SMG exposure, and this translates into buckled and bent bones in adults. This study highlights the large impact of even very short exposure periods when they coincide with critical time points of development. PMID- 29790427 TI - Simulated Microgravity Culture Enhances the Neuroprotective Effects of Human Cranial Bone-Derived Mesenchymal Stem Cells in Traumatic Brain Injury. AB - Fundamental cures of central nervous system (CNS) diseases are rarely achieved due to the low regenerative ability of the CNS. Recently, cell-based therapy using mesenchymal stem cells (MSCs) has been explored as an effective treatment for CNS diseases. Among the various tissue-derived MSCs, we have isolated human cranial bone-derived MSCs (cMSCs) in our laboratory. In addition, we have focused on simulated microgravity (MG) as a valuable culture environment of MSCs. However, detailed mechanisms underlying functional recovery from transplantation of MSCs cultured under MG conditions remain unclear. In this study, we investigated the therapeutic mechanisms of transplantation of cMSCs cultured under MG conditions in traumatic brain injury (TBI) model mice. Human cMSCs were cultured under 1G and MG conditions, and cMSCs cultured under MG conditions expressed significantly higher messenger RNA (mRNA) levels of hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta). In TBI model mice, the transplantation of cMSCs cultured under MG conditions (group MG) showed greater motor functional improvement compared with only phosphate-buffered saline administration (group PBS). Moreover, the protein expression levels of tumor necrosis factor alpha (TNF-alpha) and the Bcl-2-associated X protein (Bax)/b cell leukemia/lymphoma 2 protein (Bcl-2) ratio were significantly lower at brain injury sites in mice of group MG than those of group PBS. In addition, an in vitro study showed that the conditioned medium of cMSCs cultured under MG conditions significantly suppressed the cell death of NG108-15 cells exposed to oxidative or inflammatory stress through anti-inflammatory and antiapoptosis effects. These findings demonstrate that culturing cMSCs under simulated MG increases the neuroprotective effects, suggesting that simulated MG cultures may be a useful method for cell-based therapy strategies for CNS diseases. PMID- 29790429 TI - Effects of rapid palatal expansion (RPE) and twin block mandibular advancement device (MAD) on pharyngeal structures in Class II pediatric patients from Cluj Napoca, Romania. AB - OBJECTIVE: To compare cephalometric changes of pharyngeal structures after rapid palatal expansion (RPE) with those induced by a twin block mandibular advancement device (MAD) with palatal expansion capability. METHODS: This retrospective study investigated 55 Class II pediatric patients, divided into two groups: 29 patients treated with RPE and 26 patients treated with MAD. Lateral cephalometric measurements were compared before and after treatment. RESULTS: Changes in pharyngeal airway space were statistically significant in both groups (p < 0.001) from a pre-treatment mean distance measured between the lower posterior pharyngeal wall and the hyoid bone (LPF-H) of 25.42 mm in the MAD group and 28.62 mm in the RPE group, to a post-treatment mean LPF-H of 27.96 mm in the MAD group and 31.52 mm in the RPE group. CONCLUSION: Significant changes in pharyngeal space may be obtained in Class II patients through both rapid palatal expansion and mandibular advancement devices with palatal expansion capability. PMID- 29790428 TI - Multi-ethnic SULT1A1 copy number profiling with multiplex ligation-dependent probe amplification. AB - AIM: To develop a SULT1A1 multiplex ligation-dependent probe amplification assay and to investigate multi-ethnic copy number variant frequencies. METHODS: A novel multiplex ligation-dependent probe amplification assay was developed and tested on 472 African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish individuals. RESULTS: The frequencies of atypical total copy number (i.e., greater or less than two) were 38.7% for Hispanics, 38.9% for Ashkenazi Jewish, 43.2% for Caucasians, 53.6% for Asians and 64.1% for African-Americans. Heterozygous SULT1A1 deletion carriers (slow sulfators) were most common among Caucasians (8.4%), whereas African-Americans had the highest frequencies of three or more copies (rapid sulfators; 60.9%). CONCLUSION: Different ethnic and racial populations have varying degrees of SULT1A1-mediated sulfation activity, which warrants further research and that may have utility for drug response prediction among SULT1A1-metabolized medications. PMID- 29790431 TI - "This Time It's Different" Preparing for Release Through a Prison-Model of CoSA: A Phenomenological and Repertory Grid Analysis. AB - Circles of support and accountability (CoSA) in the prison-model begin prior to the core members' release from prison and continue with them on release in to the community. The purpose of this study was to explore the expectations of release of those convicted of a sexual offense and how this develops during their participation in the prison sessions of CoSA. The research question was to consider how the prison-model of CoSA relates to the desistance of crime, in particular the phases of desistance developed by Gobbels, Ward, and Willis. Data were collected using both phenomenological interviews and repertory grids at two different time points; prior to starting the circle in prison ( n = 9) and just before release ( n = 5). The findings suggest the prison sessions provide a sense of support and "no longer being alone" often absent in those who sexually offend. The additional prison sessions enabled the participants to experience this during their approaching release date; a stressful period that was characterized by anxiety. Further research is now required to explore whether circles in the prison-model are able to encourage and reinforce the cognitive change required for desistance, enabling the core members to successfully manage their underlying anxieties surrounding societal stigmatization. PMID- 29790430 TI - Improvement of cellular health indicators and muscle quality in older women with different resistance training volumes. AB - The main purpose of this study was to compare the effects of resistance training (RT) performed with different training volumes on phase angle (PhA), body water components, and muscle quality (MQ) in untrained older adult women. A second purpose was to assess the relationship between PhA and MQ. Sixty-two older adult women (68.6 +/- 5.0 years, 65.2 +/- 13.3 kg, 156.1 +/- 6.2 cm) were randomly assigned into one of the three groups: two training groups performed either 1 set (G1S) or 3 sets (G3S), or a control group (CG). Body water components and PhA were estimated by bioelectrical impedance (BIA). MQ was determined by dividing skeletal muscle mass estimated by dual-energy absorptiometry (DXA) by total muscle strength from three exercises. After the intervention period, both training groups demonstrated improvements (P < 0.05) when compared with CON for intracellular water, total body water, PhA, and MQ. These results suggest that RT can improve PhA, body water components, and MQ after 12 weeks of RT in untrained older women, regardless of training volume. Furthermore, changes in MQ were positively correlated with changes in PhA (r = 0.60, P < 0.01). PMID- 29790432 TI - Transoral Thyroid and Parathyroid Surgery Vestibular Approach: A Framework for Assessment and Safe Exploration. AB - The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a new approach to the central neck that avoids an anterior cervical incision. This approach can be performed with endoscopic or robotic assistance and offers access to the bilateral central neck. It has been completed safely in both North American and, even more extensively, international populations. With any new technology or approach, complications during the learning curve, expense, instrument limitations, and overall safety may affect its ultimate adoption and utility. To ensure patient safety, it is imperative to define steps that should be considered by any surgeon or group before adoption of this new approach. PMID- 29790433 TI - The influence of foot position on scrum kinetics during machine scrummaging. AB - The purpose of this study was to investigate the effect of variations in the alignment of the feet on scrum kinetics during machine scrummaging. Twenty nine rugby forwards from amateur-level teams completed maximal scrum efforts against an instrumented scrum machine, with the feet in parallel and non-parallel positions. Three-dimensional forces, the moment about the vertical axis and sagittal plane joint angles were measured during the sustained pushing phase. There was a decrease in the magnitude of the resultant force and compression force in both of the non-parallel conditions compared to parallel and larger compression forces were associated with more extended hip and knee angles. Scrummaging with the left foot forward resulted in the lateral force being directed more towards the left and the turning moment becoming more clockwise. These directional changes were reversed when scrummaging with the right foot forward. Scrummaging with the right foot positioned ahead of the left may serve to counteract the natural clockwise wheel of the live scrum and could be used to achieve an anti-clockwise rotation of the scrum for tactical reasons. However, this would be associated with lower resultant forces and a greater lateral shear force component directed towards the right. PMID- 29790435 TI - Abstracts: 23rd Annual RIMS Conference 2018. PMID- 29790434 TI - The model of professional satisfaction of nursing staff in Poland - brief communication. AB - The aim of this study was to create an empirical model that would help understand how to obtain the optimal level of professional satisfaction among Polish nurses. The study was performed using a standardized questionnaire among 1066 nurses. Descriptive and explanatory methods have been used in the statistical analysis of path-analytic approaches. The simulations showed that the model that achieved the highest measure of fit was a simple one which included 15 thematic areas, determining the varying degrees of job satisfaction of Polish nurses. The modeling approach to the process of understanding the professional satisfaction of Polish nurses allows for it to be used in the process of motivating and building organizational commitment of nurses, which creates new opportunities for effective management. This is especially important in an era of growing social needs in the care services sector, not only in Poland but throughout the world. PMID- 29790436 TI - Evaluating the role of genetic variation in the epigenome in health and disease. PMID- 29790437 TI - RIMS Abstracts 2018. PMID- 29790438 TI - RIMS Abstracts 2018. PMID- 29790439 TI - Principles of evolutionary medicine. PMID- 29790440 TI - The secret of getting ahead.... PMID- 29790441 TI - Competences management for improving performance in health organizations. AB - Purpose The purpose of this paper is to describe the design and construction of a privilege mapping system (clinical and organizational competences) of the medical staff of the Niguarda Hospital in Milan, Italy. The second aim is to measure and assess the impact of implementing an evaluation process of clinical competences at the same hospital. Design/methodology/approach The paper retraces the development and implementation of the evaluation of the privilege system, highlighting the subjects involved, the phases and outputs. Moreover, a questionnaire was distributed to 50 heads of unit involved in the planning, building and implementation of competences mapping. Five areas were investigated: competences evaluation for professional development; the impact on work organization and professional roles; professional collaboration; its impact according to context (hospital or unit) and time scale (short or long term); and ability to evaluate clinical outcome. Findings Results reveal success factors for the development and implementation of a privilege mapping system. Furthermore, the survey revealed that clinical leaders are aware of the importance of competences evaluation. In particular, they consider it as a management tool useful for professional development, for identifying excellence and planning operational activities. Originality/value Literature and practical evidence recognize the need to assess the clinical and organizational competences in order to assign tasks and responsibilities. However, there are no studies that describe the construction of systems of evaluation of privileges, as it has never been investigated as professionals perceive these tools. PMID- 29790442 TI - Closing the delivery gap. AB - Purpose The purpose of this paper is to describe the authors' experience operationalizing the care delivery value chain (CDVC) as a management and continuous quality improvement (QI) approach to strengthen HIV/AIDS services provided in Northern Togo through addressing gaps across a care continuum. Design/methodology/approach The authors led a series of discussions to develop a CDVC specific to existing HIV/AIDS services in Northern Togo. Using the CDVC framework, 28 specific gaps in service delivery were identified and integrated into a strategic QI plan. Findings At 12 months, 92 percent of delivery gaps had demonstrated improvement. The CDVC framework proved to be valuable in the following ways. First, it facilitated the first comprehensive mapping of HIV/AIDS services in the Kara region of Togo. Second, it enabled the identification of gaps or insufficiencies in the currently available services across the full continuum of care. Third, it catalyzed the creation of a strategic QI plan based on identified gaps. Research limitations/implications This case description is the authors' experience in one setting and should not be considered comparative in nature. Furthermore, the approach described may not be applicable to all initiatives and/or organizations. As described, the lack of sophisticated and comprehensive data collection systems limited the authors' ability to collect reliable data on some of the QI initiatives planned. Practical implications The operationalization of the CDVC framework is an effective approach to drive continuous QI. Originality/value Through the operationalization of the CDVC, the authors developed a new approach for assessing existing services, identifying gaps in service delivery and directing continuous QI initiatives in a strategic manner. PMID- 29790443 TI - Improvement of laboratory turnaround time using lean methodology. AB - Purpose The purpose of this paper is to discuss the implementation of lean methodology to reduce the turnaround time (TAT) of a clinical laboratory in a super speciality hospital. Delays in report delivery lead to delayed diagnosis increased waiting time and decreased customer satisfaction. The reduction in TAT will lead to increased patient satisfaction, quality of care, employee satisfaction and ultimately the hospital's revenue. Design/methodology/approach The generic causes resulting in increasing TAT of clinical laboratories were identified using lean tools and techniques such as value stream mapping (VSM), Gemba, Pareto Analysis and Root Cause Analysis. VSM was used as a tool to analyze the current state of the process and further VSM was used to design the future state with suggestions for process improvements. Findings This study identified 12 major non-value added factors for the hematology laboratory and 5 major non value added factors for the biochemistry lab which were acting as bottlenecks resulting in limiting throughput. A four-month research study by the authors together with hospital quality department and laboratory staff members led to reduction of the average TAT from 180 to 95minutes in the hematology lab and from 268 to 208 minutes in the biochemistry lab. Practical implications Very few improvement initiatives in Indian healthcare are based on industrial engineering tools and techniques, which might be due to a lack of interaction between healthcare and engineering. The study provides a positive outcome in terms of improving the efficiency of services in hospitals and identifies a scope for lean in the Indian healthcare sector. Social implications Applying lean in the Indian healthcare sector gives its own potential solution to the problem caused, due to a wide gap between lean accessibility and lean implementation. Lean helped in changing the mindset of an organization toward providing the highest quality of services with faster delivery at an optimal cost. Originality/value This paper is an effort to reduce the gap between healthcare and industrial engineering and enhancing the use of lean practices in Indian healthcare. The study is motivated toward implementing lean methodology successfully in services. PMID- 29790444 TI - Data envelopment analysis for estimating efficiency of intensive care units: a case study in Iran. AB - Purpose As hospitals are the most costly service providers in every healthcare systems, special attention should be given to their performance in terms of resource allocation and consumption. The purpose of this paper is to evaluate technical, allocative and economic efficiency in intensive care units (ICUs) of hospitals affiliated by Yazd University of Medical Sciences (YUMS) in 2015. Design/methodology/approach This was a descriptive, analytical study conducted in ICUs of seven training hospitals affiliated by YUMS using data envelopment analysis (DEA) in 2015. The number of physicians, nurses, active beds and equipment were regarded as input variables and bed occupancy rate, the number of discharged patients, economic information such as bed price and physicians' fees were mentioned as output variables of the study. Available data from study variables were retrospectively gathered and analyzed through the Deap 2.1 software using the variable returns to scale methodology. Findings The study findings revealed the average scores of allocative, economic, technical, managerial and scale efficiency to be relatively 0.956, 0.866, 0.883, 0.89 and 0.913. Regarding to latter three types of efficiency, five hospitals had desirable performance. Practical implications Given that additional costs due to an extra number of manpower or unnecessary capital resources impose economic pressure on hospitals also the fact that reduction of surplus production plays a major role in reducing such expenditures in hospitals, it is suggested that departments with low efficiency reduce their input surpluses to achieve the optimal level of performance. Originality/value The authors applied a DEA approach to measure allocative, economic, technical, managerial and scale efficiency of under-study hospitals. This is a helpful linear programming method which acts as a powerful and understandable approach for comparative performance assessment in healthcare settings and a guidance for healthcare managers to improve their departments' performance. PMID- 29790445 TI - A study of deficiencies in teamwork skills among Jordan caregivers. AB - Purpose The purpose of this paper is to present the deficiencies in teamwork skills at Jordan hospitals as seen by team members. The study aims to identify training needs to improve teamwork-related soft skills of caregivers to enhance staff satisfaction and improve quality of care. Moreover, the paper provides a methodology to identify the training needs in any healthcare workplace by repeating the same questionnaire. Design/methodology/approach A self administrated questionnaire was designed to study deficiencies in teamwork and team leadership at Jordan hospitals as seen by team members. Surveyed care providers included physicians, nursing and anesthesiologists operating in emergency departments, surgical operating rooms and intensive care units from various hospitals. Findings With a response rate of 78.8 percent, statistical analysis of collected data of opposing staff members revealed low levels of satisfaction (40.7-48 percent opposing), lack of awareness on the impact of teamwork on quality of care (15.6-22.1 percent opposing), low levels of involvement of top management (27.1-57.3 percent opposing), lack of training (52.5-69.8 percent opposing), lack of leadership skills (29.8-60 percent opposing), lack of communication (22.3-62.1 percent opposing), lack of employee involvement (37.6-50.8 percent opposing) and lack of collaboration among team members (28.6-50 percent opposing). Among the many, results illustrate the need for improving leadership skills of team leaders, improving communication and involving team members in decision making. Originality/value Several studies investigated relationships between teamwork skills and quality of care in many countries. To the authors' knowledge, no local study investigated the deficiencies of teamwork skills among Jordan caregivers and its impact on quality of care. The study provides the ground for management at Jordan hospitals and to healthcare academic departments to tailor training courses to improve teamwork skills of caregivers. Data of this study are collected from the society who is working in the field of healthcare. As the results of this are produced from a real data, it is expected that applying the recommendations will impact the society positively by enhancing the patients' satisfaction. PMID- 29790446 TI - Ninety to Nothing: a PDSA quality improvement project. AB - Purpose The purpose of this paper is to present a case study of a successful quality improvement project in an acute care hospital focused on reducing the time of the total patient visit in the emergency department. Design/methodology/approach A multidisciplinary quality improvement team, using the PDSA (Plan, Do, Study, Act) Cycle, analyzed the emergency department care delivery process and sequentially made process improvements that contributed to project success. Findings The average turnaround time goal of 90 minutes or less per visit was achieved in four months, and the organization enjoyed significant collateral benefits both internal to the organization and for its customers. Practical implications This successful PDSA process can be duplicated by healthcare organizations of all sizes seeking to improve a process related to timely, high-quality patient care delivery. Originality/value Extended wait time in hospital emergency departments is a universal problem in the USA that reduces the quality of the customer experience and that delays necessary patient care. This case study demonstrates that a structured quality improvement process implemented by a multidisciplinary team with the authority to make necessary process changes can successfully redefine the norm. PMID- 29790447 TI - Data-driven process to improve VA surgical flow. AB - Purpose During years 2014-2016, Veterans Health Administration National Surgery Office conducted a surgical flow improvement initiative (SFII) to assist low performing surgery programs to improve their operating room efficiency (ORE). The initiative was co-sponsored by VHA National Surgery Office and VHA Office of Systems Redesign and Improvement. The paper aims to discuss this issue. Design/methodology/approach An SFII algorithm, based on first-time-start (FTS), cancellation rate (CR), lag time (LT) and OR utilization, assigned an ORE performance Level (1-low to 4-high) to each VA Medical Center (VAMC). In total, 15 VAMCs with low-performance surgery programs participated in SFII to assess the current state of their surgical flow processes and used redesign methods to focus on improvement objectives. Findings At the end of the project, 14 VSAs, 40 RPIWs, 45 "90-day projects" and 73 Just-Do-It's were completed with 65 percent (158/243) improvement actions and 86 percent sites improving/sustaining all four ORE metrics. There was a statistically significant difference in improvement across the three stages (baseline, improvement, sustain) for FTS (45.6-68.7 percent; F=44.74; p<0.000); CR (16.1-9.5 percent; F=34.46; p<0.000); LT (63.1-36.3 percent; F=92.00; p<0.000); OR utilization (43.4-57.7 percent; F=6.92; p<0.001) and VAMC level (1.7-3.65; F=80.11; p<0.000). The majority developed "fair to excellent" sustainment (91 percent) and spread (82 percent) plans. The projected annual estimated return-on-investment was $27,949,966. Originality/value The SFII successfully leveraged a small number of faculty, coaches, and industrial engineers to produce significant improvement in ORE across a large national integrated health care network. This strategy can serve healthcare leaders in managing complex healthcare issues in their facilities. PMID- 29790448 TI - Enhancing outpatient appointment scheduling system performance when patient no show percent and lateness rates are high. AB - Purpose High lateness and no-show percentages pose great challenges on the patient scheduling process. Usually this is addressed by optimizing the time between patients in the scheduling process and the percent of extra patients scheduled to account for absent patients. However, since the patient no-show and lateness is highly stochastic we might end up with many patients showing up on time which leads to crowded clinics and high waiting times. The clinic might end up as well with low utilization of the doctor time. The purpose of this paper is to study the effect of scheduled overload percentages and the patient interval on the waiting time, overtime, and the utilization. Design/methodology/approach Actual data collection and statistical modeling are used to model the distribution for common dentist procedures. Simulation and validation are used to model the treatment process. Then algorithm development is used to model and generate the patient arrival process. The simulation is run for various values of basic interval scheduled time between arrivals for the patients. Further, 3D graphical illustration for the objectives is prepared for the analysis. Findings This work initially reports on the statistical distribution for the common procedures in dentist clinics. This can be used for developing a scheduling system and for validating the scheduling algorithms developed. This work also suggest a model for generating patient arrivals in simulation. It was found that the overtime increases excessively when coupling both high basic interval and high overloading percentage. It was also found that: to obtain low overtime we must reduce the basic interval. Waiting time increases when reducing the basic scheduled appointment interval and increase the scheduled overload percentage. Also doctors' utilization is increased when the basic interval is reduced. Research limitations/implications This work was done at a local clinic and this might limit the value of the modeled procedure times. Practical implications This work presents a statistical model for the various procedures and a detailed technique to model the operations of the clinics and the patient arrival time which might assist researches and developers in developing their own model. This work presents a procedure for troubleshooting scheduling problems in outpatient clinics. For example, a clinic suffering from high patient waiting time is directly instructed to slightly increase their basic scheduled interval between patients or slightly reduce the overloading percentage. Social implications This work is targeting an extremely important constituent of the health-care system which is the outpatient clinics. It is also targeting multiple objectives namely waiting times, utilization overtime, which in turn is related to the economics and doctor utilization. Originality/value This work presents a detailed modeling procedure for the outpatient clinics under high lateness and no-show and addresses the modeling procedure for the patient arrivals. This 3D graphical charting for the objectives includes a study of the multiple objectives that are of high concern to outpatient clinic scheduling interested parties in one paper. PMID- 29790449 TI - Pathology of coccidioidomycosis in llamas and alpacas. AB - Coccidioidomycosis is a fungal disease caused by either Coccidioides immitis or Coccidioides posadasii. Anecdotal evidence suggests that camelids are particularly susceptible to this disease and that a relatively large percentage of pneumonias in these animals are caused by Coccidioides spp. In a search of 21 y (1992-2013) of records from the California Animal Health and Food Safety Laboratory, we found 79 cases of coccidioidomycosis diagnosed in camelids; 66 (84%) had pneumonia and 13 (16%) had lesions only in organs other than the lungs. The organs most frequently affected were lung (84%) and liver (78%). Coccidioides spp. were the cause of pneumonia in 66 of 362 (18%) camelid cases during the study period. The lesions in affected organs were multifocal-to-coalescing pyogranulomas, which in most cases were visible grossly. Ten of the 12 formalin fixed, paraffin-embedded lung samples tested by a universal Coccidioides spp. PCR assay were positive (4 C. immitis, 2 C. posadasii); the species could not be determined in 4 of the 10 cases positive by PCR. Coccidioidomycosis is an important cause of pneumonia in camelids in California, and can be caused by either C. immitis or C. posadasii. PMID- 29790450 TI - Opisthotonos and unilateral internal hydrocephalus associated with aberrant migration of Serratospiculum sp. or Serratospiculoides sp. in a prairie falcon. AB - A juvenile, wild-caught prairie falcon ( Falco mexicanus) kept for falconry was presented to a veterinary hospital for intermittent opisthotonos and torticollis. Clinical examination, complete blood count, serum biochemistry panel, and fecal analysis were unremarkable. Clinical signs did not resolve, and the bird was euthanized 6 mo after the appearance of clinical signs. Autopsy revealed a mild, unilateral hydrocephalus and nematodes within the thoracic air sac. Histopathology demonstrated mild, unilateral hydrocephalus; scattered glial nodules; meningeal nematode sections; and meningeal and intraventricular embryonated eggs. Morphology and molecular characterization were consistent with the air sac nematode Serratospiculum or Serratospiculoides spp. Air sac nematode infection can be associated with air sacculitis or pneumonia in falcons. Aberrant migration of air sac filariid nematodes Serratospiculum or Serratospiculoides spp. into the nervous system resulting in clinical disease is rare, but should be included in the differential diagnosis of neurologic diseases in falcons. PMID- 29790451 TI - Genital mycoplasmas of healthy bitches. AB - Little is known about the presence of mycoplasmas in the genital tracts of domestic and stray bitches or in the vaginas of ovariohysterectomized (OHE) bitches. Moreover, to our knowledge, there has been no research to investigate the presence of canine vaginal mycoplasmas during the different stages of the reproductive cycle. We investigated the occurrence of mycoplasmas in the vaginas of healthy domestic and stray intact bitches, to correlate their presence with specific stages of the reproductive cycle, and to compare them with those in OHE bitches. We also investigated the presence of uterine mycoplasmas. Mycoplasmas were isolated from 41 of 122 vaginal swabs (34%) from domestic (27%) and stray (39%) bitches. Mycoplasma canis was the most commonly identified species ( n = 26; 63%), and was detected in both intact (60%) and OHE (73%) bitches. Mycoplasma isolates from the vaginas of healthy bitches did not vary during the various stages of the estrous cycle. Mycoplasmas were not detected in uterine samples. PMID- 29790452 TI - Does biological sex impact intestinal epithelial injury, small intestine permeability, gastrointestinal symptoms and systemic cytokine profile in response to exertional-heat stress? AB - This study aimed to determine the influence of biological sex on intestinal injury, permeability, gastrointestinal symptoms, and systemic cytokine profile in response to exertional-heat stress. Male (n= 13) and eumenorrheic female (n= 11) endurance runners completed 2 h running at 60% VO2max in 35 degrees C. Blood samples were collected pre- and post-exercise and during recovery to determine plasma intestinal fatty-acid binding protein (I-FABP) and systemic cytokine profile. Urinary lactulose:L-rhamnose ratio was used to determine small intestine permeability. I-FABP increased 479% pre- to post-exercise (p< 0.001), with no difference between sexes (p= 0.432). No differences between sexes were observed for small intestine permeability (p= 0.808), gut discomfort, total, upper- and lower-gastrointestinal symptoms. However, males reported significantly higher flatulence (p= 0.049) and abdominal stitch (p= 0.025) compared to females. IL-6, IL-8, IL-10 and IL-1ra increased pre- to post-exercise (p< 0.05), with no difference between sexes. However, IL-1beta increased post-exercise in males only, and was higher in males compared to females (p= 0.044). Findings suggest that when females are in the follicular phase of the menstrual cycle, biological sex has no effect on intestinal epithelial injury and permeability, and minimal effect on gastrointestinal symptoms and systemic cytokine profile in response to exertional-heat stress. PMID- 29790454 TI - XPO5 genetic polymorphisms in cancer risk and prognosis. AB - miRNAs are small noncoding RNA molecules that have a very important role in gene expression regulation and, therefore, in cell homeostasis. SNPs in certain miRNA related genes have been shown to influence cancer risk and prognosis. miRNA cellular processing is complex and involves multiple proteins. XPO5 is a key factor in this process as it is responsible for the nuclear export of the precursor pre-miRNA to the cytoplasm, where it will be further processed to its final miRNA conformation in order to be loaded to RNA inducing silencing complex to exert its regulatory effect. SNPs in miRNA machinery related genes have previously been shown to influence carcinogenesis, but the role of XPO5 SNPs in its expression and function is not yet fully understood. In our review, we elaborate comprehensively on the role of XPO5 and how polymorphisms have been shown to influence cancer risk and prognosis to date. PMID- 29790453 TI - Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations. AB - BACKGROUND: Primary congenital hypothyroidism (CH) affects about 1:3000 newborns worldwide and is mainly caused by defects in thyroid gland development (thyroid dysgenesis [TD]) or hormone synthesis. A genetic cause is identified in <10% of TD patients. The aim was to identify novel candidate genes in patients with TD using next-generation sequencing tools. PATIENT FINDINGS: Whole exome sequencing was used to study two families: a consanguineous Tunisian family (one child with severe thyroid hypoplasia) and a French family (two newborn siblings, with a thyroid in situ that was not enlarged on ultrasound at diagnosis). Variants in candidate genes were filtered according to type of variation, frequency in public and in-house databases, in silico prediction tools, and inheritance mode. Unexpectedly, three different variants of the thyroid peroxidase (TPO) gene were identified. A homozygous missense mutation (c.875C>T, p.S292F) was found in the Tunisian patient with severe thyroid hypoplasia. The two French siblings were compound heterozygotes (c.387delC/c.2578G>A, p.N129Kfs*80/p.G860R) for TPO mutations. All three mutations have been previously described in patients with goitrous CH. In these patients, treatment was initiated immediately after diagnosis, and the effect, if any, of thyrotropin stimulation of these thyroids remains unclear. CONCLUSIONS: The first cases are reported of thyroid hypoplasia at diagnosis during the neonatal period in patients with CH and TPO mutations. These cases highlight the importance of screening for TPO mutations not only in goitrous CH, but also in normal or small-size thyroids, and they broaden the clinical spectrum of described phenotypes. PMID- 29790455 TI - Successful Management of De Novo Acute Hepatitis B Virus Infection With Entecavir in a Living-Donor Liver Transplant Patient. AB - The risk of de novo hepatitis B virus infection is lower after liver transplant using hepatitis B core antibody-negative donors into negative recipients versus hepatitis B core antibody-positive donors but can occur. Here, we present a 34 year-old male patient with acute de novo hepatitis B virus that developed 7 months after successful liver transplant. The case we report here is the first in the literature with regard to both switch from tenofovir to entecavir treatment and the presentation of de novo acute hepatitis B virus after liver transplant. The switch in treatment protocol resulted in significant improvements in serologic and biochemical levels, and the patient was discharged from the hospital on day 35 after admittance. PMID- 29790456 TI - Evaluation of Neuroimaging Findings of Central Nervous System Complications in Heart Transplant Recipients. AB - OBJECTIVES: In this study, we presented neuroradiologic findings and diagnoses of neurologic complications in a series of heart transplant recipients. MATERIALS AND METHODS: A retrospective review was conducted at Baskent University Hospital. We searched the hospital and radiology databases and identified 109 heart transplant recipients. Thirty-one of these recipients had neuroradiologic evaluations secondary to presentation of neurologic symptoms after heart transplant, with 18 patients evaluated with computed tomography and 22 patients evaluated with magnetic resonance imaging (overlap of imaging-defined groups occurred in 9 recipients). Computed tomography and magnetic resonance imaging studies were retrieved from the Picture Archiving and Communication System, with each type of imaging retrospectively evaluated on consensus by 2 radiologists. RESULTS: Radiopathologic findings related to symptoms were detected in 12 of the 31 study patients. The most common abnormality was posterior reversible leukoencephalopathy syndrome (5 patients, 4.6%). The other abnormalities were ischemic stroke (3 patients, 2.8%), hemorrhagic stroke (1 patient, 0.9%), intracranial abscess (2 patients, 1.8%), and intracranial dissemination of sinusoidal fungal infection and related hemorrhagic infarct (1 patient, 0.9%). The other 19 heart transplant recipients who underwent computed tomography and/or magnetic resonance imaging for neurologic complaints showed no neuroradiologic findings related to neurologic symptoms. CONCLUSIONS: Posterior reversible leukoencephalopathy syndrome and ischemic stroke were the most common neurologic complications in our heart transplant recipients. The other complications were hemorrhagic stroke, intracranial abscess, and intracranial dissemination of sinusoidal fungal infection. Neurologic complications are common in heart transplant recipients and should be identified promptly for early treatment. For the recognition of these complications, computed tomography should be performed for initial evaluation to rule out edema or hemorrhage. However, in the presence of serious neurologic symptoms that cannot be explained by computed tomography, magnetic resonance imaging should be indicated. PMID- 29790457 TI - Comparison of Different Conditioning Regimens of Haploidentical Hematopoietic Stem Cell Transplant in Patients With Acute Myeloid Leukemia. AB - OBJECTIVES: We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant. MATERAILS AND METHODS: Twenty patients with primary acute myeloid leukemia had been randomized into busulfan/fludarabine and modified busulfan/cyclophosphamide groups. We retrospectively compared hematopoietic engraftment, regimen-related toxicity, graft-versus-host disease, transplant related mortality, leukemia-free survival, and overall survival between the groups. RESULTS: All patients achieved engraftment with 100% donor chimerism. The median times for the neutrophil and platelet engraftment in the busulfan/fludarabine and modified busulfan/cyclophosphamide groups were 14.1 versus 14.3 days and 12.7 versus 12.2 days, respectively. Significantly lower incidences of pretreatment toxicity, blood transfusion, and virus activation were observed in the busulfan/fludarabine group. Acute grade 1 graft-versus-host disease developed in all patients, which was successfully controlled with methylprednisolone. There were no significant differences in engraftment, graft versus-host disease, leukemia-free survival, and overall survival between groups. Both of these conditioning regimens achieved stable engraftment. Regimen-related toxicity in the busulfan/fludarabine group was well tolerated compared with that in the modified busulfan/cyclophosphamide group, without an increase in relapse rate. CONCLUSIONS: Our results demonstrated that myeloablative busulfan/fludarabine might be a highly effective and low-toxicity alternative for patients with acute myeloid leukemia. PMID- 29790458 TI - Relation of Preoperative and Postoperative Echocardiographic Parameters With Rejection and Mortality in Liver Transplant Patients. AB - OBJECTIVES: Survival in liver transplant after end-stage liver disease is associated with major cardiac functions. In a significant number of patients with end-stage liver disease, cardiac dysfunctions may be observed, which can include high-output heart failure, cardiac valve disease, and pulmonary venous and arterial hypertension. All of these affect perioperative survival. The aim of our study was to determine whether preoperative and postoperative echocardiographic parameters, specifically right heart-related tricuspid regurgitation, estimated systolic pulmonary arterial pressure, and tricuspid annular plane systolic excursion, are associated with rejection and mortality in liver transplant patients. MATERIALS AND METHODS: Adult patients (> 18 years old) who underwent liver transplant at our center between January 2011 and March 2017 were included in the study, with 64 patients retrospectively screened. The echocardiographic images that were taken immediately before and immediately after liver transplant were evaluated. The patients were divided into 2 groups according to rejection data and mortality. All parameters were analyzed for both variables. RESULTS: For the 24 patients with liver rejection and 40 patients without liver rejection, there were no statistically significant differences in terms of demographic data, echocardiographic parameters, and laboratory data. However, when patients were evaluated according to survival, there was a statistically significant difference between these 2 groups concerning the echocardiography parameters of systolic pulmonary arterial pressure (P = .005), tricuspid annular plane systolic excursion (P = .001), and postoperative right ventricular width (P = .01). CONCLUSIONS: Echocardiography, being a simple and easily accessible technique that is reliable in excluding pulmonary hypertension diagnosis, can be used as a guide in the evaluation of right ventricular function and tricuspid regurgitation, particularly in patients who are not hemodynamically stable before and after liver transplant. PMID- 29790459 TI - Problems With Unrelated Donors For Stem Cell Transplant and Proposed Solutions: A Single-Center Experience. PMID- 29790460 TI - Establishment of the European meningococcal strain collection genome library (EMSC-GL) for the 2011 to 2012 epidemiological year. AB - Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation. PMID- 29790461 TI - Measles outbreak in a tertiary level hospital, Porto, Portugal, 2018: challenges in the post-elimination era. AB - A measles outbreak has been occurring in a healthcare setting in Porto, Portugal, since early March 2018, posing public health challenges for a central hospital and the community. Up to 22 April, 96 cases were confirmed, 67 in vaccinated healthcare workers, mostly between 18-39 years old. Following identification of the first cases, control measures were rapidly implemented. Concomitantly, other measles cases were notified in the Northern Region of the country. No common epidemiological link was identified. PMID- 29790463 TI - Predatory Publishing: An Industry that Is Threatening Science. PMID- 29790462 TI - Negligible import of enteric pathogens by newly-arrived asylum seekers and no impact on incidence of notified Salmonella and Shigella infections and outbreaks in Rhineland-Palatinate, Germany, January 2015 to May 2016. AB - IntroductionThe 2015 refugee crisis raised concerns about an import of infectious diseases affecting the German population. Aims: To evaluate public and individual health benefits of stool screening, and explore whether importation of enteric pathogens by newly-arrived asylum seekers impacts on the host population. Methods: We used data from mandatory stool screening to determine the overall, age, sex, and country-specific prevalence of enteric bacteria and helminths. We used surveillance data to assess whether the number of incoming asylum seekers influenced notifications of salmonellosis and shigellosis in Rhineland Palatinate. Results: Salmonella were found in 0.2% (95% confidence interval (CI) 0.2-0.3%) of 23,410 samples collected from January 2015 to May 2016. Prevalence was highest in children under 5 years (0.8%; 95% CI: 0.5-1.3%). No Shigella or invasive Salmonella spp. were detected. In a subset of 14,511 samples, the prevalence of helminth infestation was 2.4% (95% CI: 2.1-2.6%), with highest proportions detected in adolescents (4.6%; 95% CI 3.8-5.4%) and among Eritreans (9.3%; 95% CI: 7.0-12.0%); in the latter particularly Schistosoma mansoni and Taenia spp. The increase in asylum applications did not increase notifications of salmonellosis and shigellosis. No transmission from asylum seekers to German residents was notified. Conclusion: Public health risk associated with imported enteric pathogens is very low overall. Addressing individual and public health risks, we recommend replacing stool screening of all newly-arrived asylum seekers by a targeted approach, with target groups and approaches being adapted if necessary. Target groups supported by our data are children, adolescents, and Eritreans. PMID- 29790464 TI - [Palliative Care in the United Kingdom: My Experience in Manchester]. PMID- 29790465 TI - Multiple Victims of Carbon Monoxide Poisoning in the Aftermath of a Wildfire: A Case Series. AB - INTRODUCTION: Carbon monoxide poisoning may occur in several contexts. MATERIAL AND METHODS: Retrospective of 37 carbon monoxide poisoning cases that underwent hyperbaric oxygen during wildfires in Funchal in August 2016. RESULTS: The studied sample included 37 patients, mean age of 38 years, 78% males. Ten were firefighters, four children and two pregnant victims. Neurological symptoms were the most reported. Median carboxyhemoglobin level was 3.7% (IQR 2.7). All received high-flow oxygen from admission to delivery of hyperbaric oxygen. Persistence of symptoms was the main indication for hyperbaric oxygen. Median time to hyperbaric oxygen was 4.8 hours (IQR 9.5), at 2.5 ATA for 90 minutes, without major complications. Discharge in less than 24 hours occurred in 92% of the cases. Thirty days follow-up: five patients presented clinical symptoms of late neurological syndrome; twelve patients were lost to follow-up. Carboxyhemoglobin levels on admission and mean time to hyperbaric oxygen were no different between those who did and did not develop the syndrome at 30 days (p = 0.44 and p = 0.58, respectively). DISCUSSION: Late neurological syndrome at 30 days occurred in 20% and no new cases were reported at 12 months. CONCLUSION: Use of hyperbaric oxygen appears to have reduced the incidence of the syndrome. This seems to be the first Portuguese series reporting use of hyperbaric oxygen in carbon monoxide poisoning due to wildfires. The authors intend to alert to the importance of referral of these patients because the indications and benefits of this treatment are well documented. This is especially important given the ever growing issue of wildfires in Portugal. PMID- 29790466 TI - Association of Anger Expression-Out with NK Cell Counts in Colorectal Cancer Patients. AB - INTRODUCTION: There is growing evidence describing the relation between psychological factors and the progression of colorectal cancer. Several mechanisms have been proposed but the one showing more promising evidence relies on the modulation of the antitumoral immune response by psychological factors, particularly through natural killer cells. We aimed to study the relation between natural killer cell count and anxiety, depression and anger state, trait and expression in 54 pre-surgical colorectal cancer patients. MATERIAL AND METHODS: We measured peripheral blood natural killer cell count and applied the State Trait Anger Expression Inventory and the Hospital Anxiety and Depression Scale to 54 pre-surgical colorectal cancer patients. We used the Mann-Whitney U test and the Kruskal-Wallis test when appropriate to compare independent groups. RESULTS: Patients with higher Anger Expression-Out had lower natural killer cell numbers than patients with lower Anger Expression-Out (p value = 0.008). No relation was found between natural killer cell levels and Anger State, Anger Trait, or Anger Expression-In. No difference in natural killer cell count was found between patients with and without clinical anxiety or depression. DISCUSSION: These results suggest that, in colorectal cancer patients, natural killer cell counts are influenced by Anger Expression-Out, but not by clinical anxiety or depression. CONCLUSION: The unregulated emotional expression might be a conditioning factor of innate immunity. Additional studies are needed to further investigate this relation and to ascertain the clinical impact of therapeutic interventions regarding emotional regulation on the anti-tumoral immune response. PMID- 29790467 TI - Prevalence of Abdominal Obesity and Excess Weight among Portuguese Children and Why Abdominal Obesity Should Be Included in Clinical Practice. AB - INTRODUCTION: Central adiposity in children has increased to a higher degree than general adiposity however it is not a routine measurement in clinical practice. We aimed to estimate the prevalence of overweight, obesity, and abdominal fat distribution and observe the prevalence of abdominal obesity among non-obese 6-10 year-old children. MATERIAL AND METHODS: Weight, height, and waist circumference were measured in a sample of 793 children (408 girls). International Obesity Task Force cut-offs were used to define overweight and obesity. Abdominal obesity was defined as waist-to-height ratio >= 0.50. Chi-square tests were used to observe the prevalence of the obesity indicators among boys and girls, and the relation between International Obesity Task Force cut-offs and abdominal obesity. RESULTS: The prevalence of overweight, including obesity among children was 21.9% (18.9 - 25.0), 6.1% (4.2 - 8.0) were obese and 21.9% (18.6 - 25.0) had a waist-to-height ratio >= 0.50. Girls had significantly higher prevalence of overweight, including obesity compared to boys (chi2 = 4.59, p = 0.03), but no differences were found for abdominal obesity according to children's gender (chi2 = 3.32, p = 0.07). A proportion of normal (8.2%; 5.9 - 10.6) and overweight children (59.5%; 50.9 - 69.0) were abdominally obese. DISCUSSION: The prevalence of general and abdominal obesity in children living in central Portugal is of concern. Many children with abdominal obesity would not be considered obese with the International Obesity Task Force cut-off points. CONCLUSION: A high proportion of abdominal obesity was observed in children with normal weight or overweight, suggesting that waist-to height ratio should be included in routine clinical practice and might be particularly useful to assess the health status of the child. PMID- 29790468 TI - [Polysaccharide of Escherichia coli in the Prevention of Recurrent Urinary Tract Infection: An Evidence-Based Review]. AB - INTRODUCTION: Recurrent urinary tract infection is frequent and it is related to morbidity, costs and growing antibiotic resistance. OM 8930 vaccine is composed by Escherichia coli polysaccharide and it is a possible prophylactic measure, but there is doubt as to its effectiveness. MATERIAL AND METHODS: We performed a systematic review in evidence-based medicine databases with rigorous bibliography selection. RESULTS: We found an effective decrease of recurrences in test groups. DISCUSSION: We recommend the administration of the vaccine as prophylaxis of recurrent cystitis. CONCLUSION: The vaccine has impact on the recurrent cystitis relapse rate. We suggest that more studies be carried out to evaluate the vaccine cost-benefit and its effectiveness in complicated urinary infections. PMID- 29790469 TI - Intraventricular Ganglioglioma Presenting with Spontaneous Hemorrhage. AB - Intraventricular gangliogliomas presenting with spontaneous hemorrhage are rare. Due to high density of important tracts lateral to the ventricular atrium, the intraparietal trans sulcal approach is a good option to remove lesions in this location. These tracts are displaced and sometimes destroyed by the presence of large masses. A 33-year-old male presented with a sudden headache and a generalized seizure. He had a left visual field hemianopia and left visual field neglect. Brain computer tomography and magnetic resonance imaging revealed a hemorrhagic tumor located in his right atrium. With the help of tractography an optimal corridor to the tumor through the intraparietal sulcus was planned. Gross total removal of a ganglioglioma was possible with recovery of visual impairment and control of epilepsy. The efficacy in using tractography as a planning tool for safe tumor removal is demonstrated with clinical, imagiological and histological data, and a surgical video. PMID- 29790470 TI - [Hidradenocarcinoma of the Scrotum with Lymph Node Metastasis]. AB - Hidradenocarcinoma is a rare neoplasm of the eccrine cells of the sweat glands, usually asymptomatic with slow growing and higher incidence between 50 and 80 years, occurring in both sexes and preferentially located in the palmar, plantar, frontal, axillary and nuchal regions. It has an aggressive behavior, with high rate of local recurrence and distance metastasis, associated with a poor prognosis. We present a case of hidradenocarcinoma of the scrotum manifested by lymph node metastasis through an exercise of clinical and histological differential diagnosis of an inguinal adenopathy in a young adult. PMID- 29790471 TI - Multiple Familial Trichoepithelioma. PMID- 29790472 TI - [Letter to the Editor: Happy Birthday Acta Medica Portuguesa! Almost 40 Years of Indexation at PubMed... (But When Will We Have a Portuguese Journal of Psychiatry Indexed at PubMed?)]. PMID- 29790473 TI - Letter to the Editor: "Limited Health Literacy in Portugal Assessed with the Newest Vital Sign" by Dagmara Paiva and Colleagues. Acta Med Port. 2017;30(12):861-869. PMID- 29790474 TI - Reply to the Letter to the Editor: "Limited Health Literacy in Portugal Assessed with the Newest Vital Sign". PMID- 29790475 TI - Letter to the Editor - Predatory Journals: Bad for All But Especially Authors from Low and Middle Income Countries. PMID- 29790476 TI - [Erratum to "Translation and Validation of the FOUR Scale for Children and its Use as Outcome Predictor: A Pilot Study"]. AB - The article "Translation and Validation of the FOUR Scale for Children and its Use as Outcome Predictor: A Pilot Study", published by Acta Medica Portuguesa on September 2017 [Acta Med Port 2017 Sep;30(9):599-607] exhibited the mistake detailed here below: On page 600, paragrapah 4, where it reads: "(...) only the last two are assessed by the GCS and depth of coma may not be accurately detected.4" It should read: "(...) GCS does not include important indicators for an adequate evaluation of coma severity, that is, it only evaluates the cortical function, not including brainstem function evaluation parameters such as respiratory pattern, pupil size and reflexes, nor eye movements; as such it may not detect the coma depth properly.4" Article published with the error: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/8052. PMID- 29790477 TI - Biolimus A9 polymer-free coated stents in high bleeding risk patients undergoing complex PCI: evidence from the LEADERS FREE randomised clinical trial. AB - AIMS: The LEADERS FREE trial has demonstrated that a polymer-free Biolimus A9 coated stent (BA9-DCS) is superior to a bare metal stent (BMS) for high bleeding risk (HBR) patients when treated with one month of dual antiplatelet therapy (DAPT). This analysis aimed to determine the impact of PCI procedure complexity on the two-year results. METHODS AND RESULTS: Six hundred and sixty-seven (667) patients enrolled in the LEADERS FREE (BA9-DCS 346, BMS 321) underwent a complex PCI, defined by one or more of eight characteristics: total stent length >=60 mm, >=3 vessels or lesions treated, >=3 stents implanted, bifurcation lesion treated with >=2 stents, chronically occluded, restenotic or saphenous vein graft lesion. Patients undergoing complex PCI were older, more often male, and presented with more ACS, diabetes, renal insufficiency, anaemia and multivessel disease. They derived major benefit from DCS over BMS for safety (16.2% vs. 21.7%, HR 0.70 [0.49-0.99], p<0.05) and for efficacy (10.8% vs. 18.1%, HR 0.54 [0.35-0.83], p<0.005). For the 1,746 patients with non-complex PCI, DCS demonstrated superior efficacy (5.3% vs. 9.9%, HR 0.52 [0.36-0.75], p<0.001, p for interaction NS) and similar safety to BMS (11.1% vs. 12.6%, NS, p for interaction NS). CONCLUSIONS: Compared to BMS, the BA9-DCS maintained both efficacy and safety benefits when used in complex PCI procedures. PMID- 29790478 TI - Validation of a novel non-hyperaemic index of coronary artery stenosis severity: the Resting Full-cycle Ratio (VALIDATE RFR) study. AB - AIMS: Randomised controlled trials have reported instantaneous wave-free ratio (iFR) to be non-inferior to fractional flow reserve (FFR) for major adverse cardiovascular events at one year; however, iFR is limited by sensitive landmarking of the pressure waveform, and the assumption that maximal flow and minimal resistance occur during a fixed period of diastole. We sought to validate the resting full-cycle ratio (RFR), a novel non-hyperaemic index of coronary stenosis severity based on unbiased identification of the lowest distal coronary pressure to aortic pressure ratio (Pd/Pa), independent of the ECG, landmark identification, and timing within the cardiac cycle. METHODS AND RESULTS: VALIDATE-RFR was a retrospective study designed to derive and validate the RFR. The primary endpoint was the agreement between RFR and iFR. RFR was retrospectively determined in 651 waveforms in which iFR was measured using a proprietary Philips/Volcano wire. RFR was highly correlated to iFR (R2=0.99, p<0.001), with a mean bias of -0.002 (95% limits of agreement -0.023 to 0.020). The diagnostic performance of RFR versus iFR was diagnostic accuracy 97.4%, sensitivity 98.2%, specificity 96.9%, positive predictive value 94.5%, negative predictive value 99.0%, area under the receiver operating characteristic curve of 0.996, and diagnostically equivalent within 1% (mean difference -0.002; 95% CI: 0.009 to 0.006, p=0.03). The RFR was detected outside diastole in 12.2% (341/2,790) of all cardiac cycles and 32.4% (167/516) of cardiac cycles in the right coronary artery where the sensitivity of iFR compared to FFR was lowest (40.6%). CONCLUSIONS: RFR is diagnostically equivalent to iFR but unbiased in its ability to detect the lowest Pd/Pa during the full cardiac cycle, potentially unmasking physiologically significant coronary stenoses that would be missed by assessment dedicated to specific segments of the cardiac cycle. PMID- 29790479 TI - Long-term clinical outcomes after bioresorbable and permanent polymer drug eluting stent implantation: final five-year results of the CENTURY II randomised clinical trial. AB - AIMS: The aim of this study was to establish the long-term safety and efficacy of a sirolimus-eluting stent with bioresorbable polymer (BP-SES; Ultimaster) by comparison with an everolimus-eluting stent with permanent polymer (PP-EES; XIENCE). METHODS AND RESULTS: CENTURY II (Clinical Evaluation of New Terumo Drug Eluting Coronary Stent System in the Treatment of Patients with Coronary Artery Disease) is a large-scale, prospective, multicentre, randomised single-blind, controlled, non-inferiority trial conducted at 58 study sites globally, including Europe, Japan and Korea, powered to prove non-inferiority for freedom from target lesion failure (TLF: cardiac death, target vessel-related myocardial infarction [MI] and target lesion revascularisation) at nine months. Patients requiring a percutaneous coronary intervention (PCI) were randomised (1:1) to BP-SES (n=551) or PP-EES (n=550). Freedom from TLF at five years was 90.0% in the BP-SES and 91.1% in the PP-EES group (p=0.54). The patient-oriented composite endpoint (all death, any MI, any revascularisation) was 24.1 and 25.6% (p=0.57) with BP-SES and PP-EES, respectively. The very late stent thrombosis rate from one to five years was especially low at 0.2% in both arms. CONCLUSIONS: This randomised clinical trial showed that the BP-SES stent was non-inferior to the benchmark PP-EES stent for TLF. Safety and efficacy measures were comparable up to five-year follow-up after PCI. PMID- 29790480 TI - Two-year clinical outcome of all-comers treated with three highly dissimilar contemporary coronary drug-eluting stents in the randomised BIO-RESORT trial. AB - AIMS: The aim of the study was to evaluate the two-year clinical outcome of all comer trial participants who were treated with two very different thin-strut biodegradable polymer versus thin-strut durable polymer drug-eluting stents (DES). Prolonged clinical outcome after discontinuation of dual antiplatelet therapy is of particular interest, given the highly dissimilar polymer types, amount, distribution, and degradation speed of both biodegradable polymer DES. METHODS AND RESULTS: The BIO-RESORT trial (NCT01674803) randomly assigned 3,514 patients to treatment with biodegradable polymer SYNERGY everolimus-eluting stents (EES) or Orsiro sirolimus-eluting stents (SES), or durable polymer Resolute Integrity zotarolimus-eluting stents (ZES). At two-year follow-up (available in 98.8%), the rate of the primary composite endpoint target vessel failure (TVF) was 8.3% in ZES versus 6.8% in EES (p=0.19) and 6.6% in SES (p=0.12). Landmark analyses at one year revealed differences between SES and ZES in the rates of target lesion revascularisation and target lesion failure (0.6% vs. 1.5%, p=0.04, and 1.1% vs. 2.4%, p=0.02, respectively) as well as other composite secondary endpoints that reached statistical significance. CONCLUSIONS: At two-year follow-up, there was no significant between-DES difference in the rates of the primary endpoint. Landmark analyses provided a signal that the use of SES versus ZES might reduce the risk of repeat revascularisation after one year follow-up. PMID- 29790481 TI - Antiviral combination therapy for cytomegalovirus infection in high-risk infants. AB - BACKGROUND: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection. METHODS: We reviewed medical records of infants <=6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). RESULTS: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads. PMID- 29790483 TI - The effect of changing one's country of residence on the decision to become an organ donor: the experience of religious immigrant women living in Sweden. AB - Aim To explore and elucidate women's knowledge of and willingness to take part in organ donation, and to explore if their opinions were changed by coming to Sweden. Methods The study was designed as a qualitative study using data from interviews with women from Bosnia and Herzegovina, Macedonia, Croatia and Kosovo. The inclusion criteria were women who were immigrants in Sweden and have lived in Sweden for more than 10 years. Five groups including forty-five women were invited to participate in the study and 39 agreed. The women were aged 29 to 73 years (mean 52.5 years). Results Regarding knowledge and information about organ donation, most women found it very important to be able to talk about such things. However, the knowledge and information about organ donation of almost all the women was at a very low level. None of the women changed their opinion on the organ donation and attitudes from their countries of origin. All women firmly emphasized and explained that by coming to another state they do not become a different person and retain all values they had and with which were born in home country. Conclusion It is important to study how to find new ways to communicate and work with minorities and vulnerable groups in order to discuss organ donation with all those who could be potential donors in the Swedish health care system. PMID- 29790482 TI - A study of enterocyte membranes during activation of apoptotic processes in chronic carrageenan-induced gastroenterocolitis. AB - Aim To investigate the lipid membranes of rat enterocytes in chronic carrageenan induced gastroenterocolitis accompanied by the activation of apoptotic processes. Methods Steady-state fluorescence spectroscopy: a study by fluorescent probes - by ortho-hydroxy derivatives of 2,5-diaryl-1,3- oxazole. Activity of apoptosis signal-regulating kinase 1 and poly (ADP-ribose) polymerase in small intestinal homogenates, blood serum levels of matrix metalloproteinase-2 and caspase-3 and the level of DNA fragmentation in small intestinal homogenates were determined. Results Biochemical analysis revealed that an activation of apoptotic processes occurred in the intestinal epithelium of rats during chronic carrageenan-induced gastroenterocolitis. The fluorescence probes showed that activation of apoptotic processes in carrageenan-induced gastroenterocolitis was accompanied by changes in polar regions of rat enterocyte membranes, while no changes were revealed in more hydrophobic regions of the membranes. Conclusion The increase in hydration of membranes was attributed to the activation of the apoptosis of enterocytes. It has been shown that a fluorescent probe (2-(2'-hydroxyphenyl)-5-phenyl-1,3 oxazole) can be used for the detection of apoptosis of enterocytes. PMID- 29790484 TI - The predictive value of the clinical sign of limited hip abduction for developmental dysplasia of the hip (DDH). AB - Aim To assess the relationship between the clinical sign of limited hip abduction and developmental dysplasia of the hip (DDH). Methods A research was conducted on 450 newborns at the Neonatal Unit at the Clinic of Gynaecology and Obstetrics and the Orthopaedics and Traumatology Clinic of the University Clinical Centre, Tuzla, between 30th August 2011 and 30th April 2012. Clinical (degree of hip abduction) and ultrasound examination of all newborns' hips were performed using the Graf method on their first day of life. Results Clinical sign of limited hip abduction showed significant predictive value for DDH. There were 67 (14.7%) newborns with the clinical sign of limited hip abduction, of which 26 (5.7%) were on the left hip, 11 (2.4%) on the right hip and 30 (6.6%) on both hips. Limited hip abduction had a positive predictive value (PPV) of 40.3% and a negative predictive value (NPV) of 80.4% for DDH. Conclusion Limited hip abduction, especially unilateral, is a useful and important clinical sign of DDH. Doctors, who perform the first examination of the child after birth, would have to pay attention to this clinical sign. Newborns with this clinical sign would have to go to an ultrasound examination of the hips for further diagnosis. PMID- 29790485 TI - Bibliometric Analysis of Tumor Immunotherapy Studies. AB - BACKGROUND Cancer immunotherapy is the use of the immune system to treat cancer. After years of research, there have been a significant number of publications in this field. We analyzed the literature and performed a hotspot analysis to identify important areas of future scientific research. MATERIAL AND METHODS Articles (2945) related to cancer immunotherapy published in the past 3 years were selected as the research sample. BICOMB software was then used to retrieve the high-frequency words and construct a text/co-word matrix. Next, gCLUTO software was used to analyze the matrix by double-clustering and visual analysis, in a strategy of hotspot identification. RESULTS We constructed a text and co word matrix composed of 40 high-frequency words and 2945 articles and generated a hotspot "peak map" based on double-clustering analysis. The strategic coordinates were set by use of a co-word matrix and clustering analysis. The distribution of organs or disease and the subclass of cancer immunotherapy were analyzed. CONCLUSIONS In this study, we classified the hot-spots of "tumor immunotherapy" into 6 categories and 8 aspects. Calculation and analysis revealed that the field of tumor immunotherapy shows a slight trend of polarization, and the immune checkpoint inhibitor PD1 blocker shows the greatest potential for future development. PMID- 29790486 TI - [Simplicity or complexity of the radiopharmaceutical production process in the light of optimization of radiation protection of staff - 99mTc vs. 18F]. AB - BACKGROUND: A radiopharmaceutical is a combination of a non-radioactive compound with a radioactive isotope. Two isotopes: technetium-99m (99mTc) and fluorine-18 (18F) are worth mentioning on the rich list of isotopes which have found numerous medical applications. Their similarity is limited only to the diagnostic area of applicability. The type and the energy of emitted radiation, the half-life and, in particular, the production method demonstrate their diversity. The 99mTc isotope is produced by a short-lived nuclide generator - molybdenum-99 (99Mo)/99mTc, while 18F is resulting from nuclear reaction occurring in a cyclotron. A relatively simple and easy handling of the 99Mo/99mTc generator, compared to the necessary use a cyclotron, seems to favor the principle of optimizing the radiological protection of personnel. The thesis on the effect of automation of both the 18F isotope production and the deoxyglucose labelling process on the optimization of radiological protection of workers compared to manual procedures during handling of radiopharmaceuticals labelled with 99Tc need to be verified. MATERIAL AND METHODS: Measurements of personal dose equivalent Hp(0.07) were made in 5 nuclear medicine departments and 2 radiopharmaceuticals production centers. High-sensitivity thermoluminescent detectors (LiF: Mg, Cu, P MCP-N) were used to determine the doses. RESULTS: Among the activities performed by employees of both 18F-fluorodeoxyglucose (18F-FDG) production centers and nuclear medicine departments, the manual quality control procedures and labelling of radiopharmaceuticals with 99mTc isotope manifest the greatest contribution to the recorded Hp(0.07). CONCLUSIONS: The simplicity of obtaining the 99mTc isotope as well as the complex, but fully automated production process of the 18F-FDG radiopharmaceutical optimize the radiation protection of workers, excluding manual procedures labelling with 99mTc or quality control of 18F-FDG. Med Pr 2018;69(3):317-327. PMID- 29790488 TI - Monitoring after radiofrequency ablation of liver tumors: contrast-enhanced ultrasound (CEUS) vs. contrast-enhanced computer tomography (CECT), two days after procedure. AB - AIM: Our research evaluated the ability of contrast-enhanced ultrasound (CEUS) and contrast enhanced computer tomography (CECT), performed 48 h after radiofrequency ablation (RFA), to detect residual tumor tissue. As recently published studies have evaluated periprocedural CEUS performed within 24 h after procedure and their results were not satisfactory, it seems that postponing the control test by one day could increase the sensitivity of both methods. PATIENTS AND METHODS: We evaluated 33 patients with 37 lesions, who met the criteria for our study. The criteria were 1) the treated lesion is sonographically viewable and 2) the patient underwent both CEUS and CECT control 48 h after treatment and additional follow-up 3 months later by CECT. Presence of residual tumor tissue and the size of necrosis were recorded and compared to the results of 3-months CECT. RESULTS: Nine residues were present in our group. CEUS and CECT showed similar sensitivity (66.7% and 77.8%, respectively) and identical specificity (both 96.4%) for detection of residual tumor tissue. CEUS significantly underestimated the size of necrosis in comparison to CECT (on average by 2.4 mm, P=0.0005). Over the 3-months follow-up period the size of necrosis decreased in all patients (on average by 7.2 mm, P<0.0001). CONCLUSION: The quality of tumor residue detection in 48-h CEUS was comparable to that of 48-h CECT. This finding suggests the CEUS being a feasible substitute for CECT. Both methods show reasonable sensitivity; therefore this timing seems to be appropriate for the first post-treatment control while also allowing for early retreatment if residual tumor tissue is found. PMID- 29790487 TI - [1,4-diaminobenzene and diphenylamine-induced severe methemoglobinaemia treated by hyperbaric oxygen therapy - Case report]. AB - Methemoglobin is an oxidized form of hemoglobin that is not capable of carrying oxygen. Exposure to exogenous oxidizing agents can cause severe methemoglobinemia and subsequent hypoxia. This article presents the rare case of a 23-year old patient with methemoglobinemia of 54.2% of total hemoglobin, induced by workplace exposure to 1,4-diaminobenzene and diphenylamine. Following the hyperbaric oxygen therapy the patient was discharged in good general condition and referred to a district hospital for observation. Med Pr 2018;69(3):345-350. PMID- 29790490 TI - A multi-walled carbon nanotube-based magnetic molecularly imprinted polymer as a highly selective sorbent for ultrasonic-assisted dispersive solid-phase microextraction of sotalol in biological fluids. AB - A modified multiwalled carbon nanotube-based magnetic molecularly imprinted polymer (MWCNT-MMIP) was synthesized and applied for selective extraction and preconcentration of sotalol (SOT) in biological fluid samples by using ultrasonic assisted dispersive solid-phase microextraction (UA-DSPME). The synthetic particles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis, vibrating sample magnetometry (VSM) and Fourier transform infrared spectroscopy (FTIR). The screening of UA-DSPME was preliminarily performed by Plackett-Burman design (PBD) and, subsequently, central composite design (CCD) under response surface methodology (RSM) was used individually for evaluation of the significant factors and their possible interaction effects on the adsorption process. Batch mode adsorption studies were performed to evaluate the adsorption kinetics, adsorption isotherms, and selective recognition of MWCNT-MMIPs. The adsorption equilibrium of SOT using MWCNT-MMIPs could be well-defined with the Langmuir isotherm model and the maximum adsorption capacity was calculated to be 79.36 mg g-1. Under optimized conditions, the SOT was selectively and effectively extracted in real biological samples and good linearity was obtained with correlation coefficients (R2) over 0.996 and the detection limit (S/N = 3) was 0.31 ng mL-1. The average recoveries of the spiked human urine and plasma samples at four concentration levels of SOT ranged from 94.60-102.50 and 97.40-101.60 percent, respectively, and the relative standard deviation was found to be lower than 4.50%. The results illustrated that the proposed MWCNT-MMIPs@UA-DSPME extraction method coupled with HPLC-UV determination could be applied for sensitive and selective analysis of trace SOT in biological fluid samples. PMID- 29790489 TI - Inhibitory effect of hop fractions against Gram-positive multi-resistant bacteria. A pilot study. AB - AIM: Our research focused on the antimicrobial effects of purified hop (Humulus lupulus L.) fractions including alpha-bitter acids (humulones), beta-bitter acids (lupulones) and xanthohumol, and a commercial CO2 hop extract of bitter acids against reference and multi-resistant strains of Gram-positive and Gram-negative bacteria and against selected yeast strains. METHODS: In vitro testing of antimicrobial activity was performed according to standard testing protocols (EUCAST). The effects of hop extracts on bacterial/yeast strains at concentrations below MICs were also determined and the antimicrobial potential of hop extracts was compared with selected antibiotics using optical density measurement. RESULTS: The fractions were effective not only against reference strains of Gram-positive bacteria but, more importantly, against their methicillin- and vancomycin-resistant variants. No antimicrobial effect was detected against Gram-negative bacterial strains. Among the tested substances, xanthohumol was identified as the hop fraction with the most potent antimicrobial properties. It was also found that hop substances exerted their antimicrobial effects at concentrations considerably lower than the determined MICs, with the strongest effect in case of alpha-bitter acids in enterococci. CONCLUSION: The search for and research of new compounds with antimicrobial properties represents a possible solution to the current global problem of bacterial resistance. Our data suggest a desirable activity of hop fractions against some multi-resistant bacterial strains. Thus, hops might find use as a source of potential antimicrobial agents applicable in both human and veterinary medicine. PMID- 29790491 TI - Advancements in microfluidic technologies for isolation and early detection of circulating cancer-related biomarkers. AB - Early stage detection of cancer is essential for the improved long-term survival of patients. Currently, costly, extensively complex and invasive procedures, such as surgical tissue biopsies, are used for cancer screening. Thus, over the past few decades, advancements in microfluidics and lab-on-a-chip approaches have been made to develop minimally invasive and miniaturized platforms to identify and segregate circulating cancer biomarkers such as exosomes, circulating tumor cells (CTCs) and cell-free DNA (cfDNA) from body fluids. Our study presents a comprehensive overview of all such microfluidics based approaches for point-of care cancer diagnostics, which have proven to require significantly reduced sample volumes with cost effective and minimally invasive criteria. We have also discussed the need for integrated and more efficient devices to further advance these technologies to be suitable for liquid biopsy in the clinical settings. PMID- 29790492 TI - Cobalt complex catalyzed atom-economical synthesis of quinoxaline, quinoline and 2-alkylaminoquinoline derivatives. AB - A new phosphine-free Co(ii) complex-catalyzed synthesis of various quinoxalines via dehydrogenative coupling of vicinal diols with both o-phenylenediamines and 2 nitroanilines is reported. This complex was also effective for the synthesis of quinolines. The practical aspect of this catalytic system was revealed by the one pot synthesis of 2-alkylaminoquinolines. PMID- 29790494 TI - Channel current analysis estimates the pore-formation and the penetration of transmembrane peptides. AB - We measured the current signal of the transmembrane model peptides using the barrel-stave, toroidal pore, and penetration models in order to establish a precise assignment of the channel signals. In addition, we analyzed the spike signals to estimate the membrane penetration of model cell-penetration peptides of different lengths. PMID- 29790493 TI - Quantum dot conjugated nanobodies for multiplex imaging of protein dynamics at synapses. AB - Neurons communicate with each other through synapses, which show enrichment for specialized receptors. Although many studies have explored spatial enrichment and diffusion of these receptors in dissociated neurons using single particle tracking, much less is known about their dynamic properties at synapses in complex tissue like brain slices. Here we report the use of smaller and highly specific quantum dots conjugated with a recombinant single domain antibody fragment (VHH fragment) against green fluorescent protein to provide information on diffusion of adhesion molecules at the growth cone and neurotransmitter receptors at synapses. Our data reveals that QD-nanobodies can measure neurotransmitter receptor dynamics at both excitatory and inhibitory synapses in primary neuronal cultures as well as in ex vivo rat brain slices. We also demonstrate that this approach can be applied to tagging multiple proteins to simultaneously monitor their behavior. Thus, we provide a strategy for multiplex imaging of tagged membrane proteins to study their clustering, diffusion and transport both in vitro as well as in native tissue environments such as brain slices. PMID- 29790495 TI - Tunable laser interference lithography preparation of plasmonic nanoparticle arrays tailored for SERS. AB - The facile preparation of arrays of plasmonic nanoparticles over a square centimeter surface area is reported. The developed method relies on tailored laser interference lithography (LIL) that is combined with dry etching and it offers means for the rapid fabrication of periodic arrays of metallic nanostructures with well controlled morphology. Adjusting the parameters of the LIL process allows for the preparation of arrays of nanoparticles with a diameter below hundred nanometers independently of their lattice spacing. Gold nanoparticle arrays were precisely engineered to support localized surface plasmon resonance (LSPR) with different damping at desired wavelengths in the visible and near infrared part of the spectrum. The applicability of these substrates for surface enhanced Raman scattering is demonstrated where cost effective, uniform and reproducible substrates are of paramount importance. The role of deviations in the spectral position and the width of the LSPR band affected by slight variations of plasmonic nanostructures is discussed. PMID- 29790496 TI - Luminescence properties of mechanochemically synthesized lanthanide containing MIL-78 MOFs. AB - Three metal-organic framework (MOF) compounds, Ln0.5Gd0.5{C6H3(COO)3}; Ln = Eu, Tb, and Dy with a MIL-78 structure, have been synthesized by a solvent-free mechanochemical method from stoichiometric mixtures of benzene 1,3,5 tricarboxylic acid, C6H3(COOH)3, also known as trimesic acid, and the respective lanthanide carbonates, Ln2(CO3)3.xH2O, Ln = Eu, Gd, Tb and Dy. MIL-78 (Ln0.5Gd0.5) shows the characteristic red, green, and yellow luminescence of Eu3+, Tb3+, and Dy3+, respectively. Efficient intramolecular energy transfer from the ligand triplet state to the excited states of Ln3+ ions can be observed. The lifetimes and quantum yields of these compounds are studied and discussed in detail. Among the three compounds, the Tb3+ containing compound shows the longest lifetime and highest quantum yield due to a smaller contribution from non radiative decay pathways and better matching of the lowest triplet energy level of the benzenetricarboxylate ligand and the resonance level of Tb3+. PMID- 29790497 TI - An enzymatic reaction mediated glucose sensor activated by MnO2 nanosheets acting as an oxidant and catalyst. AB - A self-regulated smart system would be highly desirable for analyte detection, in which a specific environment for detection could be self-modulated and the required reagents could also be in situ generated without further addition. Here, we have designed an intelligent glucose detection system composed of glucose, glucose oxidase (GOx), MnO2 and 3,3',5,5'-tetramethylbenzidine (TMB), based on the enzymatic oxidation of glucose and dual roles of synthesized MnO2 nanosheets acting as both an oxidant and catalyst. Upon the addition of glucose/GOx, the MnO2 nanosheets partially decompose due to H2O2in situ generated via glucose oxidation. Following the addition of TMB, a typical color reaction occurs under slightly acidic conditions, thereby enabling the colorimetric determination of glucose. For this system, the specific conditions and the required reagents for glucose detection can be self-modulated and self-generated via the enzymatic oxidation of glucose to gluconic acid and H2O2, performing smart self-regulated functions. This is an outstanding advantage of our designed glucose sensing system. Moreover, the present sensing system responds to glucose quickly and sensitively with a detection limit of 100 nM, and is stable and specific toward glucose detection. PMID- 29790498 TI - Rooibos tea extracts inhibit osteoclast formation and activity through the attenuation of NF-kappaB activity in RAW264.7 murine macrophages. AB - Rooibos tea is a naturally sweet and aromatic tea that is native to the Western Cape province of South Africa. Rooibos is usually fermented to produce the traditional reddish brown colour and has been found to have numerous health benefits. These include beneficial effects on osteoblasts; however, its effects on osteoclast formation and activity are unknown. Osteoclasts are large, multinucleated cells responsible for bone resorption. Binding of RANKL to its receptor on osteoclast precursors triggers the NF-kappaB signalling pathway leading to the formation of osteoclasts. Certain bone destructive diseases, such as osteoporosis, are characterised by overactive osteoclasts. The inhibition of osteoclasts may offer a potential mode to prevent these diseases. The polyphenol contents of both fermented and unfermented tea extracts were similar although the radical scavenging activity of fermented rooibos tea was lower. Both tea extracts were not cytotoxic and inhibited osteoclast formation. Fermented rooibos tea extract caused a greater reduction in osteoclast resorption and the associated gene expression when compared with unfermented rooibos tea. Both tea extracts were shown to attenuate NF-kappaB activity. Fermented rooibos was found to have a more potent inhibitory effect on osteoclasts than unfermented rooibos extract and therefore may have a beneficial effect on bone health. PMID- 29790499 TI - Mass spectrometric detection of iron nitrosyls, sulfide oxidation and mycothiolation during nitrosylation of the NO sensor [4Fe-4S] NsrR. AB - The bacterial nitric oxide (NO)-sensing transcriptional regulator NsrR binds a [4Fe-4S] cluster that enables DNA-binding and thus repression of the cell's NO stress response. Upon exposure to NO, the cluster undergoes a complex nitrosylation reaction resulting in a mixture of iron-nitrosyl species, which spectroscopic studies have indicated are similar to well characterized low molecular weight dinitrosyl iron complex (DNIC), Roussin's Red Ester (RRE) and Roussin's Black Salt (RBS). Here we report mass spectrometric studies that enable the unambiguous identification of NsrR-bound RRE-type species, including a persulfide bound form that results from the oxidation of cluster sulfide. In the presence of the low molecular weight thiols glutathione and mycothiol, glutathionylated and mycothiolated forms of NsrR were readily formed. PMID- 29790500 TI - Application of lanthanide luminescence in probing enzyme activity. AB - Enzymes play critical roles in the regulation of cellular function and are implicated in numerous disease conditions. Reliable and practicable assays are required to study enzyme activity, to facilitate the discovery of inhibitors and activators of enzymes related to disease. In recent years, a variety of enzyme assays have been devised that utilise luminescent lanthanide(iii) complexes, taking advantage of their high detection sensitivities, long luminescence lifetimes, and line-like emission spectra that permit ratiometric and time resolved analyses. In this Feature article, we focus on recent progress in the development of enzyme activity assays based on lanthanide(iii) luminescence, covering a variety of strategies including Ln(iii)-labelled antibodies and proteins, Ln(iii) ion encapsulation within defined peptide sequences, reactivity based Ln(iii) probes, and discrete Ln(iii) complexes. Emerging approaches for monitoring enzyme activity are discussed, including the use of anion responsive lanthanide(iii) complexes, capable of molecular recognition and luminescence signalling of polyphosphate anions. PMID- 29790501 TI - Catalysis of photooxidation reactions through transformation between Cu2+ and Cu+ in TiO2-Cu-MOF composites. AB - Novel porous TiO2@Cu3(BTC)2 composites, which were synthesized using ionic liquids (ILs) as solvents, exhibited excellent activity for photooxidation of styrene to 4-aryl tetralones and promoting the Glaser coupling reaction with O2 under light irradiation. It was discovered that the transformation between Cu2+ and Cu+ was crucial for enhancing the photocatalytic performance. PMID- 29790502 TI - Inhibition of tau-derived hexapeptide aggregation and toxicity by a self assembled cyclic d,l-alpha-peptide conformational inhibitor. AB - Aggregation and accumulation of amyloid beta and tau proteins to plaques and neurofibrillary tangles are the key pathogenic events in Alzheimer's disease. Here, we studied the capability of the cyclic d,l-alpha-peptide CP-2 as a conformational inhibitor of different amyloids to cross-interact with tau-derived AcPHF6 peptide and inhibit its aggregation, membrane perturbation and toxicity. PMID- 29790503 TI - A voltammetric method for Fe(iii) in blood serum using a screen-printed electrode modified with a Schiff base ionophore. AB - Herein, a potent electrochemical ionophore (SMS-2) based on a Schiff base has been used for the modification of a screen-printed electrode (SPE). The modified disposable electrode can selectively detect ferric ions in an aqueous medium. Redox behavior of the proposed strip was characterized using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Incorporation of the ligand in the ink of the SPE enhanced the analytical performance of the electrode, and its surface modification was confirmed by SEM and EDX analysis. Shifting/quenching of the cathodic peak potential of the ionophore after binding with Fe(iii) ions was used to detect and measure the ferric ion concentration. This sensor can identify Fe(iii) in the detection range from 0.625 MUM to 7.5 MUM. The modified SPE can selectively detect ferric ions in the presence of many other interfering ions and has been successfully used to determine the Fe(iii) content in blood serum samples. The metal-ionophore complex structure was optimized using DFT calculations to study the energetics of the metal-ionophore interactions. PMID- 29790505 TI - Heterogeneous nucleation and growth of highly crystalline imine-linked covalent organic frameworks. AB - A heterogeneous nucleation and growth method is reported to synthesize imine linked covalent organic frameworks (COFs). Excellent crystallinity and a high surface area are obtained. The introduction of heterogeneous nuclei suppresses the fast precipitation of amorphous structures at the early stage while promoting the crystallization of COFs during the growth process. PMID- 29790504 TI - Molecularly imprinted nanoparticles for inhibiting ribonuclease in reverse transcriptase polymerase chain reaction. AB - Molecularly imprinted nanoparticles (nanoMIPs) are synthesized via a solid-phase approach using RNase as the template. The feasibility of employing the nanoMIPs as RNase inhibitor is successfully demonstrated in reverse transcriptase polymerase chain reaction (RT-PCR) assays, suggesting the tailor-made nanomaterials are very promising for use in routine biological assays. PMID- 29790506 TI - Pyrenyl-carbon nanostructures for scalable enzyme electrocatalysis and biological fuel cells. AB - The objective of this article is to demonstrate the electrode geometric area based scalability of pyrenyl-carbon nanostructure modification for enzyme electrocatalysis and fuel cell power output using hydrogenase anode and bilirubin oxidase cathode as the model system. PMID- 29790507 TI - A novel liquid chromatography detector based on a dielectric barrier discharge molecular emission spectrometer with online microwave-assisted hydrolysis for determination of dithiocarbamates. AB - A novel detector for liquid chromatography (LC) for the determination of dithiocarbamate (DTC) fungicides is presented with a miniaturized dielectric barrier discharge-microplasma molecular emission spectrometer and an online microwave-assisted hydrolysis reactor. DTCs in the sample/standard solutions together with SnCl2 were pumped to the reactor to be converted to CS2 with high efficiency, which was then separated from the liquid phase and transformed for the detection of the specific molecular emission at 257.49 nm by the spectrometer. Under optimized conditions, the performance of this new detector was evaluated by its determination of different types of DTC including mancozeb, thiram, zineb, propineb, and metiram, and the limit of detection (LOD) values were found to be in the range 0.1-1.0 MUg mL-1. The results from 20 test vegetable and fruit samples determined with the proposed method agreed well with those obtained using the standard headspace gas chromatography-electron capture detector (GC-ECD) method. Preliminary experimental results showed that the proposed method provided slightly higher LOD values than those obtained using GC ECD. Most importantly, the new LC detector could detect each DTC chemical, whereas the traditional method could not distinguish between analytes of different subclasses of DTC. PMID- 29790508 TI - Towards an atomistic understanding of disordered carbon electrode materials. AB - Disordered nanoporous and "hard" carbons are widely used in batteries and supercapacitors, but their atomic structures are poorly determined. Here, we combine machine learning and DFT to obtain new atomistic insight into carbonaceous energy materials. We study structural models of porous and graphitic carbons, and Na intercalation as relevant for sodium-ion batteries. PMID- 29790509 TI - Palladium-catalyzed cocyclotrimerization of arynes with a pyramidalized alkene. AB - The metal-catalyzed [2+2+2] cocycloaddition of arynes with pyramidalized alkenes is presented. The generation of a highly reactive pyramidalized alkene in the presence of a large excess of in situ-produced arynes led to the corresponding cocyclotrimerization (1 : 2)-adducts in good yields, establishing the first example of a palladium-based reaction of a pyramidalized alkene. PMID- 29790510 TI - Effects of nanostructuring on the bond strength and disorder in V2O5 cathode material for rechargeable ion-batteries. AB - We have investigated the nanostructuring effects on the local structure of V2O5 cathode material by means of temperature dependent V K-edge X-ray absorption fine structure measurements. We have found that the nanostructuring largely affects V O and V-V bond characteristics with a general softening of the local V-O and V-V bonds. The obtained bond strengths correlate with the specific capacity shown by the different systems, with higher capacity corresponding to softer atomic pairs. The present study suggests the key role of local atomic displacements in the diffusion and storage of ions in cathodes for batteries, providing important information for designing new functional materials. PMID- 29790511 TI - Ion collision-induced chemistry in pure and mixed loosely bound clusters of coronene and C60 molecules. AB - Ionization, fragmentation and molecular growth have been studied in collisions of 22.5 keV He2+- or 3 keV Ar+-projectiles with pure loosely bound clusters of coronene (C24H12) molecules or with loosely bound mixed C60-C24H12 clusters by using mass spectrometry. The heavier and slower Ar+ projectiles induce prompt knockout-fragmentation - C- and/or H-losses - from individual molecules and highly efficient secondary molecular growth reactions before the clusters disintegrate on picosecond timescales. The lighter and faster He2+ projectiles have a higher charge and the main reactions are then ionization by ions that are not penetrating the clusters. This leads mostly to cluster fragmentation without molecular growth. However, here penetrating collisions may also lead to molecular growth but to a much smaller extent than with 3 keV Ar+. Here we present fragmentation and molecular growth mass distributions with 1 mass unit resolution, which reveals that the same numbers of C- and H-atoms often participate in the formation and breaking of covalent bonds inside the clusters. We find that masses close to those with integer numbers of intact coronene molecules, or with integer numbers of both intact coronene and C60 molecules, are formed where often one or several H-atoms are missing or have been added on. We also find that super-hydrogenated coronene is formed inside the clusters. PMID- 29790512 TI - Probing the interaction between solid benzene and water using vacuum ultraviolet and infrared spectroscopy. AB - We present results of a combined vacuum ultraviolet (VUV) and infrared (IR) photoabsorption study of amorphous benzene : water mixtures and layers to investigate the benzene-water interaction in the solid phase. VUV spectra of 1 : 1, 1 : 10 and 1 : 100 benzene : water mixtures at 24 K reveal a concentration dependent shift in the energies of the 1B2u, 1B1u and 1E1u electronic states of benzene. All the electronic bands blueshift from pure amorphous benzene towards gas phase energies with increasing water concentration. IR results reveal a strong dOH-pi benzene-water interaction via the dangling OH stretch of water with the delocalised pi system of the benzene molecule. Although this interaction influences the electronic states of benzene with the benzene-water interaction causing a redshift in the electronic states from that of the free benzene molecule, the benzene-benzene interaction has a more significant effect on the electronic states of benzene. VUV spectra of benzene and water layers show evidence of non-wetting between benzene and water, characterised by Rayleigh scattering tails at wavelengths greater than 220 nm. Our results also show evidence of benzene-water interaction at the benzene-water interface affecting both the benzene and the water electronic states. Annealing the mixtures and layers of benzene and water show that benzene remains trapped in/under water ice until water desorption near 160 K. These first systematic studies of binary amorphous mixtures in the VUV, supported with complementary IR studies, provide a deeper insight into the influence of intermolecular interactions on intramolecular electronic states with significant implications for our understanding of photochemical processes in more realistic astrochemical environments. PMID- 29790513 TI - Dynamics in a one-dimensional ferrogel model: relaxation, pairing, shock-wave propagation. AB - Ferrogels are smart soft materials, consisting of a polymeric network and embedded magnetic particles. Novel phenomena, such as the variation of the overall mechanical properties by external magnetic fields, emerge consequently. However, the dynamic behavior of ferrogels remains largely unveiled. In this paper, we consider a one-dimensional chain consisting of magnetic dipoles and elastic springs between them as a simple model for ferrogels. The model is evaluated by corresponding simulations. To probe the dynamics theoretically, we investigate a continuum limit of the energy governing the system and the corresponding equation of motion. We provide general classification scenarios for the dynamics, elucidating the touching/detachment dynamics of the magnetic particles along the chain. In particular, it is verified in certain cases that the long-time relaxation corresponds to solutions of shock-wave propagation, while formations of particle pairs underlie the initial stage of the dynamics. We expect that these results will provide insight into the understanding of the dynamics of more realistic models with randomness in parameters and time dependent magnetic fields. PMID- 29790514 TI - Theoretical investigation of M@Pb122- and M@Sn122- Zintl clusters (M = Lrn+, Lun+, La3+, Ac3+ and n = 0, 1, 2, 3). AB - The positions of lawrencium (Lr), lutetium (Lu), actinium (Ac) and lanthanum (La) in the periodic table have been a controversial topic for quite some time. According to studies carried out by different groups with their justifications, these elements may potentially be placed in the d-block, p-block or all four in a 15 element f-block. The present work looks into this issue from a new perspective, which involves encapsulation of these four elements into Zintl ion clusters, Pb122- and Sn122-, followed by the determination of the structural, thermodynamic and electronic properties of these endohedral M@Pb122- and M@Sn122- clusters (M = Lrn+, Lun+ with n = 0, 1, 2, 3) using first principles based density functional theory (DFT). These parameters are compared with similar clusters encapsulated La3+ and Ac3+ ions in order to seek out similarities and differences to draw conclusions about their placement in the periodic table. For the first time the structural, energetic, and electronic properties of these metal atom/ion encapsulated Pb122- and Sn122- clusters have been investigated thoroughly. Structural parameters such as bond distances, geometry and symmetry, electronic properties viz. the density of states, the molecular orbital ordering, the electron localization function, bond critical point properties and charge distributions have been analyzed. Additionally, the thermodynamic property of the binding energy during the encapsulation process has also been calculated. All M@Pb12+ and M@Sn12+ (M = Lr and Lu) clusters form stable 18 bonding electron magic number systems with shell closing. They show negative values of binding energy and relatively large HOMO-LUMO energy gaps indicating the stability of such clusters. All the calculated parameters for Lr encapsulated clusters closely match with the corresponding calculated parameters of Lu encapsulated clusters, confirming the similarity between Lr and Lu metal atoms in various oxidation states, though their atomic ground state valence electronic configurations are different. The effect of spin orbit coupling has also been investigated using the ZORA approach. It is interesting to discover that La and Ac showed striking similarities to Lr and Lu with respect to all the properties investigated and have formed a stable 18-electron system. PMID- 29790516 TI - Ultrafast excited state decay of natural UV filters: from intermolecular hydrogen bonds to a conical intersection. AB - Kynurenines (KNs) are natural UV filters of the human eye lens, protecting the eye tissues from solar UV radiation. Key points of their effective protection are the intramolecular charge transfer (ICT) in the excited state and the fast dissipation of absorbed light energy into heat via the intermolecular H-bonds. Herein we report that the introduction of an unsaturated double bond in the amino acid side chain, operating as an ICT-enhancing electron donor group, drastically accelerates the internal conversion (IC) due to a conical intersection (CI) between the potential energy surfaces of the excited and ground states. Our photophysical study of a deaminated KN (carboxyketoalkene, CKA), an intrinsic product of KN thermal decomposition, demonstrates an unusually fast excited state decay in a broad range of solvents of different polarity and proticity. The detailed analysis of interactions in the excited state by different computational techniques revealed that the changes in molecular structure - the twist of the carbonyl group from the plane of the aromatic ring followed by the formation of two mutually orthogonal conjugated substructures - are responsible for the CI of the excited and ground state potential energy surfaces. Intermolecular H-bonds facilitate the transition to the CI, but do not play a crucial role in the fast decay of the excited state. An extremely fast and efficient IC in CKA opens the way for the design of new types of organic UV filters and their applications in material science, cosmetics and medicine. PMID- 29790517 TI - The rotation-vibration spectrum of methyl fluoride from first principles. AB - Accurate ab initio calculations on the rotation-vibration spectrum of methyl fluoride (CH3F) are reported. A new nine-dimensional potential energy surface (PES) and dipole moment surface (DMS) have been generated using high-level electronic structure methods. Notably, the PES was constructed from explicitly correlated coupled cluster calculations with extrapolation to the complete basis set limit and considered additional energy corrections to account for core valence electron correlation, higher-order coupled cluster terms beyond perturbative triples, scalar relativistic effects, and the diagonal Born Oppenheimer correction. The PES and DMS are evaluated through robust variational nuclear motion computations of pure rotational and vibrational energy levels, the equilibrium geometry of CH3F, vibrational transition moments, absolute line intensities of the nu6 band, and the rotation-vibration spectrum up to J = 40. The computed results show excellent agreement with a range of experimental sources, in particular the six fundamentals are reproduced with a root-mean square error of 0.69 cm-1. This work represents the most accurate theoretical treatment of the rovibrational spectrum of CH3F to date. PMID- 29790520 TI - Molecular-based upconversion in homo/heterogeneous liquids and in micro/nanostructured solid materials. AB - Radiation upconversion can be an elegant and efficient strategy to minimize waste in energy harvesting and storage processes. The upconversion based on triplet triplet annihilation processes of molecular dyes is a very versatile approach, but it requires a systematic photophysical characterization of the systems to optimize the upconversion yields and develop materials for technological applications. This paper represents an overview of the work carried out in our laboratories for the study and characterization of a molecular dye pair, 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphyrin platinum(ii) (PtOEP) and 1,3,6,8 tetraphenylpyrene (TPPy), suitable as the sensitizer and emitter, respectively, in a triplet-triplet annihilation based upconversion process. The investigation has been carried out in various media with increasing complexity. First, we used the dye pair to characterize the UC-efficiencies in homogeneous solvents of different viscosities and in oil-in-water microemulsions; then we explored the possibility to achieve upconversion in solid materials, like nanostructured silica matrices and liquid filled microcapsules. The possibility to achieve upconversion emission even in confined and rigid media has been confirmed and can inspire further applications of the process. PMID- 29790522 TI - Catalytic promiscuity of the non-native FPP substrate in the TEAS enzyme: non negligible flexibility of the carbocation intermediate. AB - The TEAS, one of the sesquiterpene cyclases (FPPC), shows enzyme promiscuity that can effectively catalyze both the natural substrate (trans,trans)-FPP and the non native (cis,trans)-FPP substrate to generate diverse products/byproducts. So far, the catalytic mechanism of the promiscuous substrate is still unclear. In this work, QM(DFT)/MM MD simulations were employed to illuminate the predominant 1,6 closure pathway reaction mechanism for the non-native substrate (cis,trans)-FPP, while the 1,10-closure pathway is the major reaction for the native substrate. It has been revealed that the catalytic promiscuity of TEAS is mostly attributable to the notable conformational dynamics of the branching intermediate bisabolyl cation. The comparative studies to FSTS (another widely studied FPPC) further indicate that the intrinsic intermediate flexibility in TEAS is highly correlated to the plasticity of the enzyme active site pocket contour. Finally, we propose a general picture for controlling the promiscuity and fidelity in FPPC catalysis, including substrate folding, intermediate flexibility and key residues. PMID- 29790524 TI - Alleviating luminescence concentration quenching in lanthanide doped CaF2 based nanoparticles through Na+ ion doping. AB - Luminescence concentration quenching, mainly due to a cross relaxation (CR) process between lanthanide ions (Ln3+), widely occurs in Ln3+ doped luminescent materials, setting a limit in the dopant content of Ln3+ emitters to withhold the brightness. Here, we introduced Na+ ions into the CaF2 host lattice codoped with Nd3+ emitters that alleviates concentration quenching greatly. And we show that the optimal dopant concentration of Nd3+ in colloidal CaF2:Nd nanoparticles increased from 10 to 30 mol%, resulting in an ~32 times near-infrared (NIR) (1052 nm) brightness under 800 nm laser irradiation. Our mechanistic investigation suggests that the enhancement of NIR photo-luminescence (PL) could be attributed to not only the increasing crystallinity of nanoparticles but also the reducing concentration quenching of Nd3+ by improving the dopant distribution of Nd3+ ions in the CaF2 lattice, as evidenced by the high angle annular dark field images. These result in the optimal concentration increase to produce brightness enhancement greatly. This strategy can be utilized for other Ln3+ doped CaF2 based nanomaterials for bio-imaging. PMID- 29790525 TI - DNA decorated Cu9S5 nanoparticles as NIR light responsive drug carriers for tumor chemo-phototherapy. AB - Recently, near-infrared (NIR) light responsive drug delivery systems have attracted much attention for tumor therapy. Herein, we have successfully constructed a smart nanocarrier system Cu9S5-PEI-DNA-DOX (labelled as CPD-DOX) based on the self-assembly of hydrophobic Cu9S5 nanoparticles (NPs), poly(ethylene imine) (PEI), double-stranded DNA (dsDNA) segments and the anti cancer drug doxorubicin (DOX). Among them, Cu9S5 NPs can serve as a nano transducer for absorbing and converting near-infrared light to heat. Then, the hydrophobic layer of Cu9S5 NPs is coated with the dendritic polymer PEI through a simple approach. According to the temperature of the tumor tissue and the photothermal effect of Cu9S5 NPs, we specially designed a DNA sequence with a suitable melting temperature for NIR-light-promoted denaturation of DNA helices and drug release when DOX intercalated into the dsDNA through noncovalent interaction. Notably, the DOX-loaded dsDNA can be decorated on the surface of Cu9S5 NPs by convenient electrostatic adsorption rather than chemical bonding. The experimental results show that dsDNA can maintain a stable helical structure under physiological conditions but unzip the helix to release DOX upon NIR irradiation. Therefore, DOX can be safely delivered and released into cancer cells to exert anticancer effects. Based on in vitro cell cytotoxicity experiments, the CPD-DOX system has a synergistic effect for cancer cell apoptosis or death because of both the cytotoxicity of light-triggered DOX release and the Cu9S5-NP-mediated photothermal ablation effect. It is expected that the facile synthesis and low cost nanocarrier can improve the anticancer effect in contrast to the single chemotherapy or photothermal therapy mode. PMID- 29790526 TI - Food-grade monoglyceride oil foams: the effect of tempering on foamability, foam stability and rheological properties. AB - Foams with a continuous oil phase may be stabilized using crystalline particles. Those systems are compelling because of their potential in edible oil structuring, modifying sensorial properties and creating healthier food products. This study aimed to relate oleogel (unwhipped state) properties to oil foam (whipped state) properties using a monoglyceride-sunflower oil model system. The properties of crystal-oil mixtures were influenced by time and temperature during preparation and storage. Therefore, oleogels were prepared using different tempering protocols and their resulting microstructure was investigated with rheology, differential scanning calorimetry and X-ray diffraction. The corresponding oil foams were characterized in terms of foamability and foam stability. The properties of both systems were studied immediately after preparation as well as after 4 weeks of storage. We demonstrated that there is a large influence of the time-temperature history on the foam properties. Partially crystallized mixtures were shown to form weaker structures which capture more air because of their lower viscosity and as crystallization would preferentially take place at the interface. They were characterized by larger bubbles and were less stable and firm. It is proposed that their rheological properties are mainly dominated by interfacial contributions. Fully crystallized and stored monoglyceride-oil mixtures were seen to form stronger gel networks which included less air, contained smaller air bubbles and were stable during storage. It is hypothesized that these samples also included an important bulk gelation contribution. PMID- 29790528 TI - Three-dimensionally interconnected Si frameworks derived from natural halloysite clay: a high-capacity anode material for lithium-ion batteries. AB - On account of its high theoretical capacity, silicon (Si) has been regarded as a promising anode material for Li-ion batteries. Extracting Si content from earth abundant and low-cost aluminosilicate minerals, rather than from artificial silica (SiO2) precursors, is a more favorable and practical method for the large scale application of Si anodes. In this work, three-dimensionally interconnected (3D-interconnected) Si frameworks with a branch diameter of ~15 nm are prepared by the reduction of amorphous SiO2 nanotubes derived from natural halloysite clay. Benefiting from their nanostructure, the as-prepared 3D-interconnected Si frameworks yield high reversible capacities of 2.54 A h g-1 at 0.1 A g-1 after 50 cycles, 1.87 A h g-1 at 0.5 A g-1 after 200 cycles, and 0.97 A h g-1 at 2 A g-1 after a long-term charge-discharge process of 500 cycles, remarkably outperforming the commercial Si material. Further, when the as-prepared Si frameworks and commercial LiCoO2 cathodes are paired in full cells, a high anode capacity of 0.98 A h g-1 is achieved after 100 cycles of rapid charge/discharge at 2 A g-1. This work provides a new strategy for the synthesis of high-capacity Si anodes derived from natural aluminosilicate clay. PMID- 29790527 TI - Protective activity of tovophyllin A, a xanthone isolated from Garcinia mangostana pericarps, against acetaminophen-induced liver damage: role of Nrf2 activation. AB - Garcinia mangostana L. (GM, family Guttiferae) is one of the most widely recognized tropical fruits. GM is a wealthy pool of xanthones that exhibit a wide range of bioactivities. Tovophyllin A (TA) separated from GM pericarps was tested for its efficacy to ameliorate acetaminophen (APAP)-induced liver injury. Mice were injected with a single dose of APAP with or without TA pretreatment. The protective effects of TA against APAP-induced liver damage were evident through amelioration of serum indices of hepatotoxicity and improvement of hepatic histopathologic lesions. TA has antioxidant activity because it inhibited APAP induced lipid peroxidation and improved the antioxidant capacity of the liver. Also, TA enhanced the mRNA expression of nuclear erythroid-related factor 2 (Nrf2) and its target genes. Protein expression of Nrf2 and heme oxygenase-1 was enhanced remarkably in TA-pretreated groups. TA suppressed activation of nuclear factor-kappa B (NF-kappaB) and the subsequent release of pro-inflammatory cytokines. In conclusion, TA has a marked protective activity against APAP induced hepatotoxicity which may be linked to its ability to activate Nrf2 and inhibit the NF-kappaB signaling pathway. PMID- 29790530 TI - Balancing the acidity of the pendant urea arm of bis-heteroleptic ruthenium(ii) complex containing pyridyl triazole for improved oxyanion recognition. AB - Two new RuII-based bis-heteroleptic ditopic receptors 1[PF6]2 (C44H34F12N10OP2Ru) and 2[PF6]2 (C40H27F17N10OP2Ru), decorated with a 1-naphthyl and pentafluorophenyl urea pendant arm, respectively, along with the previously reported 3[PF6]2 (C40H31F13N10OP2Ru), containing a pendant 4-fluorophenyl urea unit and 4[PF6]2, devoid of a pendant urea arm, have been studied to establish the role of urea proton acidity on the sensing and extraction of oxyanions in the presence of triazole C-H as an additional hydrogen bonding motif. 1H-NMR, isothermal titration calorimetry (ITC) and photophysical experiments show selective binding of 1[PF6]2 and 2[PF6]2 toward oxyanions such as phosphates (e.g., H2PO4- and HP2O73-) and carboxylates (e.g., CH3CO2- and PhCO2-) like 3[PF6]2. This generalizes the role of triazole C-H and urea in the RuII-based bis heteroleptic ditopic receptors towards recognition of such anions. Interestingly, complex 1[PF6]2 having intermediate acidic urea -NH protons showed the highest binding affinity with phosphates as compared to the other urea analogues 2[PF6]2 and 3[PF6]2 as well as the non-urea analogue, 4[PF6]2 (C32H24F12N8P2Ru). Moreover, 2[PF6]2 having the most acidic -NH protons showed higher binding affinity towards carboxylates as compared to that of 1[PF6]2/3[PF6]2. Detailed photo-physical studies revealed that 1[PF6]2 is a farsuperior and more selective H2PO4- sensor compared to 2[PF6]2/3[PF6]2/4[PF6]2, as evidenced by the higher degree of amplification of RuII center-based MLCT emission, greater change in excited state lifetime, lower detection limit and higher degree of selectivity. Furthermore, 1[PF6]2 also acts as a moderate liquid-liquid extraction agent of H2PO4-, CH3CO2- and PhCO2- anions, which was comparable to 3[PF6]2 and much higher as compared to 2[PF6]2/4[PF6]2. PMID- 29790529 TI - Dimethylmagnesium revisited. AB - A compilation of solvent-free homometallic methyl compounds of the type MMex (x = 1-6) is provided and categorised according to their method of characterisation (powder or single crystal X-ray diffraction, gas electron diffraction (GED), reactivity, unconfirmed). Recrystallisation of polymeric [MgMe2]n from excess GaMe3 led to the formation of highly pure [MgMe2]n suitable for single crystal X ray crystallographic studies. Transient Mg(GaMe4)2 could be detected in excess GaMe3 by NMR spectroscopy, but its isolation as Mg(GaMe4)2 failed. On one occasion tetrameric [Mg(GaMe4)(OMe)]4 could be isolated as a minor co-product. The formation of single-crystalline [MgMe2]n from a saturated ethereal solution could be reproduced as reported earlier by Coates et al. Assessing the reactivity of potassium methoxide methanol adduct toward Mg(AlMe4)2, the protonolysis reaction with MeOH gave unprecedented [Mg(AlMe4){Al(OMe)2Me2}]2 featuring one 8 membered [MgOAlO]2 metalloxane ring and two 4-membered metallacycles. PMID- 29790531 TI - Mechanism of H adatoms improving the O2 reduction reaction on the Zn-modified anatase TiO2 (101) surface studied by first principles calculation. AB - First principles calculations were performed to cast insight into the mechanism of the improvement of O2 reduction reaction (ORR) activity by Zn and H interstitials on the anatase TiO2 (101) surface. For the Zn-modified anatase TiO2 (101) surface, both surface and subsurface Zn interstitials could contribute to O2 adsorption and dissociation, but the dissociation barriers of O2 molecules are still too high, which limits the ORR activity. After a H adatom is introduced onto the Zn-modified anatase TiO2 (101) surface, the highest energy barriers are greatly reduced compared with those of the Zn-modified surface. Meanwhile, it is observed that the dissociation barriers decrease almost linearly with the increase of the charge difference of adsorption O2 between initial and transition state configurations. Specifically, subsurface Zn and surface H interstitials facilitate O2 dissociation and subsequent oxidation reactions, and further frequency analysis shows that these dissociation processes are frequent even at the room temperature of 300 K. In a word, this work provides a theoretical support to design a high ORR activity catalyst of the TiO2 nanocrystal comparable to precious Pt catalysts. PMID- 29790532 TI - Brimstone chemistry under laser light assists mass spectrometric detection and imaging the distribution of arsenic in minerals. AB - Singly charged As2n+1 ion clusters (n = 2-11) were generated from elemental arsenic by negative-ion laser-ablation mass spectrometry. The overall abundance of the gaseous As ions generated upon laser irradiation was enhanced nearly a hundred times when As-bearing samples were admixed with sulfur. However, sulfur does not act purely as an inert matrix: irradiating arsenic-sulfur mixtures revealed a novel pathway to generate and detect a series of [AsSn]- clusters (n = 2-6). Intriguingly, the spectra recorded from As2O3, NaAsO2, Na3AsO4, cacodylic acid and 3-amino-4-hydroxyphenylarsonic acid together with sulfur as the matrix were remarkably similar to that acquired from an elemental arsenic and sulfur mixture. This result indicated that arsenic sulfide cluster-ions are generated directly from arsenic compounds by a hitherto unknown pathway. The mechanism of elemental sulfur extracting chemically bound arsenic from compounds and forming [AsSn]- clusters is enigmatic; however, this discovery has a practical value as a general detection method for arsenic compounds. For example, the method was employed for the detection of As in its minerals, and for the imaging of arsenic distribution in minerals such as domeykite. LDI-MS data recorded from a latent image imprinted on a piece of paper from a flat mineral surface, and wetting the paper with a solution of sulfur, enabled the localization of arsenic in the mineral. The distribution of As was visualized as false-color images by extracting from acquired data the relative intensities of m/z 139 (AsS2-) and m/z 171 (AsS3-) ions. PMID- 29790534 TI - Evidence for the natural origins of anomalously high chromium levels in soils of the Cecina Valley (Italy). AB - The problem of high levels of chromium is one of the most important issues in soils of the Mediterranean area, in particular those deriving from ophiolitic parent materials. Very often the chromium concentration is greater than the threshold values of legislation on soil pollution and the knowledge of the origin of contamination (natural or anthropogenic) is important to formulate risk characterization. This study evaluated the soils from three coastal areas of the Cecina Valley (Tuscany, Italy) to understand the origin of chromium in the soils, where high levels of hexavalent chromium were found in well and spring waters of the areas. The main soil characteristics and the correlations among the values of chromium and nickel were determined. Chromium speciation was evaluated by synchrotron radiation X-ray absorption spectroscopy. The results showed the presence of only trivalent chromium in soil and a positive linear correlation between chromium and nickel (e.g. r = 0.76 for the Marina di Bibbona-Bolgheri area), corroborating the hypothesis of a geogenic origin of contamination. This hypothesis was also supported by the low CRI index for the soils with high total Cr content, indicating a higher presence of refractory minerals in the Marina di Bibbona-Bolgheri area than Cecina and Collemezzano areas. The refractory material found in soils was attributed to the presence of ophiolite outcrops in the surroundings and their sedimentary remnants. The weathering of ultramafic-derived constituents and their regional-scale transport are believed to be responsible for the enrichment of chromium and nickel in the investigated soils. PMID- 29790537 TI - Physical defects in basement membrane-mimicking collagen-IV matrices trigger cellular EMT and invasion. AB - In fibrosis and cancer, degradation of basement membrane (BM) and cell invasion are considered as key outcomes of a cellular transformation called epithelial mesenchymal transition (EMT). Here, we pose a converse question - can preexisting physical defects in the BM matrix cause EMT in normal epithelial cells? On a BM mimicking matrix of collagen-IV-coated polyacrylamide (PA) gel, we have discovered a reverse phenomenon in which preexisting defects trigger EMT in normal epithelial cells. Through spatiotemporal measurements and simulations in silico, we demonstrate that the EMT precedes cellular mechanoactivation on defective matrices, but they occur concurrently on stiff matrices. The defect dependent EMT caused cell invasion though a stroma-mimicking collagen-I layer, which could be disabled through MMP9 inhibition. Our findings reveal that the known BM degradation caused by cellular EMT and invasion is not a one-way process. Instead, normal epithelial cells can exploit physical defects in the BM matrix to undergo disease-like cellular transformations. PMID- 29790538 TI - Highly efficient bluish green organic light-emitting diodes of iridium(iii) complexes with low efficiency roll-off. AB - Two novel iridium(iii) complexes Ir(BTBP)2mepzpy and Ir(BTBP)2phpzpy were successfully synthesized, in which 2',6'-bis(trifluoromethyl)-2,4'-bipyridine (BTBP) was used as the main ligand, and 2-(3-methyl-1H-pyrazol-5-yl)pyridine (mepzpy) and 2-(3-2-(3-phenyl-1H-pyrazol-5-yl))pyridine (phpzpy) were introduced as the ancillary ligands, respectively. Both Ir(iii) complexes displayed bluish green emission peaks at 486 and 487 nm with high quantum efficiencies of 0.73 and 0.69, respectively. The organic light-emitting diodes (OLEDs) with the structure of ITO/HATCN (hexaazatriphenylenehexacarbonitrile, 5 nm)/TAPC (bis[4-(N,N ditolylamino)-phenyl]cyclohexane, 40 nm)/Ir(BTBP)2mepzpy or Ir(BTBP)2phpzpy (10 wt%): 2,6-DCzPPy (2,6-bis(3-(9H-carbazol-9-yl)phenyl)pyridine, 10 nm)/TmPyPB (1,3,5-tri[(3-pyridyl)-phen-3-yl]benzene, 30 nm)/LiF (1 nm)/Al (100 nm) exhibited high efficiencies with low efficiency roll-off. Especially, the device based on the Ir(BTBP)2mepzpy complex achieved a maximum current efficiency of 58.17 cd A-1 and a maximum external quantum efficiency of 25.33% with Commission Internationale de 1'Eclairage coordinates of (0.19, 0.43). These results indicate that novel cyclometalated Ir(iii) complexes for high efficiency OLEDs with low efficiency roll-off were obtained by our rational design. PMID- 29790536 TI - DNA interactions of non-chelating tinidazole-based coordination compounds and their structural, redox and cytotoxic properties. AB - Novel tinidazole (tnz) coordination compounds of different geometries were synthesised, whose respective solid-state packing appears to be driven by inter- and intramolecular lone pairpi interactions. The copper(ii) compounds exhibit interesting redox properties originating from both the tnz and the metal ions. These complexes interact with DNA through two distinct ways, namely via electrostatic interactions or/and groove binding, and they can mediate the generation of ROS that damage the biomolecule. Cytotoxic studies revealed an interesting activity of the dinuclear compound [Cu(tnz)2(MU-Cl)Cl]27, which is further more efficient towards cancer cells, compared with normal cells. PMID- 29790539 TI - Uranium(iii) complexes supported by hydrobis(mercaptoimidazolyl)borates: synthesis and oxidation chemistry. AB - The reaction of [UI3(thf)4] with the sodium or lithium salts of hydrobis(2 mercapto-1-methylimidazolyl)borate ligands ([H(R)B(timMe)2]-) in a 1 : 2 ratio, in tetrahydrofuran, gave the U(iii) complexes [UI{kappa3-H,S,S' H(R)B(timMe)2}2(thf)2] (R = H (1), Ph (2)) in good yields. Crystals of [UI{kappa3 H,S,S'-H(Ph)B(timMe)2}2(thf)2] (2) were obtained by recrystallization from a tetrahydrofuran/acetonitrile solution, and the ion-separated uranium complex [U{kappa3-H,S,S'-H(Ph)B(timMe)2}2(CH3CN)3][I] (3-I) was obtained by dissolution of 2 in acetonitrile followed by recrystallization. One-electron oxidation of 2 with AgBPh4 or I2 resulted in the formation of the cationic U(iv) complexes [U{kappa3-H,S,S'-H(Ph)B(timMe)2}3][X] (X = BPh4 (6-BPh4), I (6-I)), due to a ligand redistribution process. These complexes are the first examples of homoleptic poly(azolyl)borate U(iv) complexes. Treatment of complex 2 with azobenzene led to the isolation of crystals of the U(iv) compound [UI{kappa3 H(Ph)B(timMe)2}2(kappa2-timMe)] (7). Treatment of 2 with pyridine-N oxide (pyNO) led to the formation of the uranyl complex [UO2{kappa2-S,S'-H(Ph)B(timMe)2}2] (8) and of complex 6-I, while from the reaction of [U{kappa3 H(Ph)B(timMe)2}2(thf)3][BPh4] (5) with pyNO, the oxo-bridged U(iv) complex [{U{kappa3-H(Ph)B(timMe)2}2(pyNO)}2(MU-O)][BPh4]2 (9) was also obtained. In the U(iii) and U(iv) complexes, the bis(azolyl)borate ligands bind to the uranium center in a kappa3-H,S,S' coordination mode, while in the U(vi) complex the ligands bind to the metal in a kappa2-S,S' mode. The presence of UH-B interactions in the solid-state, for the nine-coordinate complexes 1, 2, 3, 6 and 7 and for the eight-coordinate complex 9, was supported by IR spectroscopy and/or X-ray diffraction analysis. PMID- 29790540 TI - Luminescent copper(i) complexes with bisphosphane and halogen-substituted 2,2' bipyridine ligands. AB - Heteroleptic [Cu(P^P)(N^N)][PF6] complexes, where N^N is a halo-substituted 2,2' bipyridine (bpy) and P^P is either bis(2-(diphenylphosphino)phenyl)ether (POP) or 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) have been synthesized and investigated. To stabilize the tetrahedral geometry of the copper(i) complexes, the steric demands of the bpy ligands have been increased by introducing 6- or 6,6'-halo-substituents in 6,6'-dichloro-2,2'-bipyridine (6,6' Cl2bpy), 6-bromo-2,2'-bipyridine (6-Brbpy) and 6,6'-dibromo-2,2'-bipyridine (6,6' Br2bpy). The solid-state structures of [Cu(POP)(6,6'-Cl2bpy)][PF6], [Cu(xantphos)(6,6'-Cl2bpy)][PF6].CH2Cl2, [Cu(POP)(6-Brbpy)][PF6] and [Cu(xantphos)(6-Brbpy)][PF6].0.7Et2O obtained from single crystal X-ray diffraction are described including the pressure dependence of the structure of [Cu(POP)(6-Brbpy)][PF6]. The copper(i) complexes with either POP or xantphos and 6,6'-Cl2bpy, 6-Brbpy and 6,6'-Br2bpy are orange-to-red emitters in solution and yellow-to-orange emitters in the solid state, and their electrochemical and photophysical properties have been evaluated with the help of density functional theory (DFT) calculations. The emission properties are strongly influenced by the substitution pattern that largely affects the geometry of the emitting triplet state. [Cu(POP)(6,6'-Cl2bpy)][PF6] and [Cu(xantphos)(6,6'-Cl2bpy)][PF6] show photoluminescence quantum yields of 15 and 17%, respectively, in the solid state, and these compounds were tested as luminophores in light-emitting electrochemical cells (LECs). The devices exhibit orange electroluminescence and very short turn on times (<5 to 12 s). Maximum luminance values of 121 and 259 cd m-2 for [Cu(POP)(6,6'-Cl2bpy)][PF6] and [Cu(xantphos)(6,6'-Cl2bpy)][PF6], respectively, were achieved at an average current density of 100 A m-2. External quantum efficiencies of 1.2% were recorded for both complexes. PMID- 29790541 TI - Supramolecular arrays by the self-assembly of terpyridine-based monomers with transition metal ions. AB - Hierarchical construction of a highly ordered supramolecular array has been, in general, a challenge due to the complexation of building blocks and the hard-to control weak interactions. Herein, we present a type of well-ordered nanoribbon, which was self-assembled via shape complimentary and hydrophobic effects from the bowl-shaped supramolecular components, which were synthesized by combining designer terpyridine-based monomers and two different metal ions (Ru2+, Zn2+). Interestingly, switching counter ions or changing monomer concentrations, a transformation between a uniform nanosphere and nanoribbon occurred. This opens a door to fabricate readily tailorable, large-scale, supramacromolecular materials. PMID- 29790542 TI - A rare example of a compact heteroleptic cyclometalated iridium(iii) complex demonstrating well-separated dual emission. AB - A series of [Ir(C^N)2(NN)][PF6] complexes in which NN is 5-(4-ethynylphenyl)-2,2' bipyridine has been synthesized and characterized by spectroscopic methods. All novel complexes exhibit unique singlet-triplet dual emission in solution with two well-separated emission bands. The mechanism of dual emission has been elucidated on the basis of experimental data and confirmed by TDDFT calculations. PMID- 29790543 TI - A bi-metallic MOF catalyst via sensitive detection & adsorption of Fe3+ ions for size-selective reaction prompting. AB - A cadmium(ii)-based MOF, Cd-MDIP, was successfully prepared by hydrothermal reaction between the tetra-carboxylic ligand 5,5'-methylenebisophthalic acid (H4MDIP) and cadmium perchlorate. The X-ray crystal structure analysis showed that there are two uncoordinated carboxyl groups in each ligand and a 1D elliptical channel along the [001] direction. Because of the existence of uncoordinated carboxyl groups within open frameworks, Cd-MDIP exhibited a high sensitivity (Stern-Volmer constant KSV = 4.13 * 104 L mol-1) and a low detection limit (80 nM) for Fe3+ ions in pure water, which is much lower than the national standard for Fe3+ in daily drinking water (5.4 MUM) set by the Ministry of Environmental Protection of P. R. China. Most importantly, Cd-MDIP also featured the ultrahigh adsorption of Fe3+ in aqueous solution that cannot be destroyed even by EDTA/base. Importantly, the MOF material (Cd-MDIP?Fe3+) after adsorbing Fe3+ could act as the first example of an excellent bi-metallic Lewis-acid catalyst for the cyanosilylation reaction of aromatic aldehydes in a size selective fashion, and its efficiency was almost 10-times higher than that of the original Cd-MDIP. PMID- 29790546 TI - Dietary fibers, prebiotics, and exopolysaccharides produced by lactic acid bacteria: potential health benefits with special regard to cholesterol-lowering effects. AB - The gastrointestinal (GIT) microbiota, which plays a crucial role in human health, is influenced by a number of factors including diet. Consumption of specific dietary ingredients, such as dietary fibers and prebiotics, is an avenue by which the microbiota can be positively modulated. These substances may also reduce serum cholesterol levels through various mechanisms. Interest has increased in methods of reducing blood cholesterol level, because dyslipidemia is recognized as a contributory risk factor for the development of cardiovascular diseases. Several drugs have been developed for the treatment of hypercholesterolemia; however, undesirable side effects were observed, which have caused concerns about their long-term therapeutic use. Alternatively, many nonpharmacological approaches were tested to reduce elevated serum cholesterol levels. Dietary fibers and prebiotics have particularly beneficial effects on the GIT microbiome, and can also reduce serum cholesterol level through various mechanisms. Lactic acid bacteria (LAB) are potentially capable of synthesizing different polysaccharides, e.g. exopolysaccharides (EPS), which may play a role as prebiotics. LAB-based EPS have the potential to affect the gastrointestinal microbiome and reduce cholesterol. However, as dietary fibers comprise a complex group of substances with remarkably diverse structures, properties, and impacts, EPS also differ greatly and show a multitude of beneficial health effects. This review discusses the current knowledge related to the effects of dietary fibers and prebiotics on the human GIT microbiome, the prebiotic properties of EPS produced by LAB, and the health-promoting benefits of these polymers with special emphasis being given to cholesterol lowering. PMID- 29790547 TI - Melissa officinalis L. ethanolic extract inhibits the growth of a lung cancer cell line by interfering with the cell cycle and inducing apoptosis. AB - Melissa officinalis is a plant from the family Lamiaceae, native in Europe particularly in the Mediterranean region. Given our interest in identifying extracts and compounds capable of inhibiting tumor cell growth, and given the antioxidant content and the high consumption of Melissa officinalis in Portugal, this study aimed to test the tumor cell growth inhibitory activity of five different extracts of this plant (aqueous, methanolic, ethanolic, hydromethanolic and hydroethanolic) in three human tumor cell lines: MCF-7, AGS and NCI-H460. All extracts decreased cell growth in all cell lines in a concentration-dependent manner. The ethanolic extract was the most potent one, presenting a GI50 concentration of approximately 100.9 MUg mL-1 in the NCI-H460 lung cancer cells. This extract was characterized by LC-DAD-ESI/MS regarding its phenolic composition, revealing rosmarinic acid as the most abundant compound. The GI75 concentration of this extract affected the cell cycle profile of these cells. In addition, both the GI50 and the GI75 concentrations of the extract induced cellular apoptosis. Moreover, treatment of NCI-H460 cells with this extract caused a decrease in pro-caspase 3 and an increase in p53 levels. This study emphasizes the relevance of the study of natural products as inhibitors of tumor cell growth. PMID- 29790548 TI - Role of flower-like ultrathin Co3O4 nanosheets in water splitting and non-aqueous Li-O2 batteries. AB - The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are both fundamental and essential processes for various energy conversion and storage systems. The kinetics of ORR and OER play a critical role in their energy efficiency and practicality. Here, flower-like ultrathin Co3O4 nanosheets synthesized through a facile solvothermal technique were studied as a bifunctional catalyst for both water splitting and non-aqueous Li-O2 batteries. Due to the novel structure and highly active {110} and {100} exposed facets, which can effectively facilitate mass transfer and enhance catalytic capability, Co3O4 nanosheets exhibit better stability and higher ORR/OER activity than Co3O4 nanoparticles, Co3O4 bulks, Pt/C, and RuO2 in alkaline solution. More importantly, Li-O2 batteries with ultrathin Co3O4 nanosheets catalyst can enhance the initial discharge capacity from 6400 to 8600 mA h g-1 and improve the cyclability up to 160 cycles at 500 mA g-1. Unexpectedly, XRD and UV/Vis techniques suggest that the main product in Co3O4 nanosheets based cathodes is LiOH, with resulting LiOH also demonstrating reversible formation/decomposition behavior, rather than Li2O2 in pure Super P based cathodes. Further investigation confirms that Co3O4 can also catalyze the electrolyte decomposition responsible for the formation of LiOH, and a reaction mechanism was illustrated. This work highlights that the traditional high-efficiency bifunctional catalyst in aqueous media may not be suitable for non-aqueous Li-O2 batteries, and the effect of catalyst on electrolyte besides the discharge product should also be carefully considered for the design of more stable and practical Li-O2 systems. PMID- 29790549 TI - A MOF-derived method to construct well-arranged porous nanosheets for lithium ion batteries. AB - In this work, we report a facile route to fabricate a ZnCo2O4 nanosheet derived from metal-organic frameworks. The as-prepared ZnCo2O4 nanosheet material for lithium-ion batteries shows an excellent electrochemical performance. The obtained ZnCo2O4 nanosheet delivers a high reversible capacity of 1640.8 mA h g-1 at a current density of 100 mA g-1 after 50 cycles. More importantly, even at a current density of 1500 mA g-1, the electrode material still exhibits a discharge capacity of 581.3 mA h g-1 after 190 cycles. These results demonstrate that the ZnCo2O4 nanosheet shows great potential as an anode material for lithium ion batteries. PMID- 29790550 TI - Cs2CO3-promoted methylene insertion into disulfide bonds using acetone as a methylene source. AB - An efficient halogen-free Cs2CO3-promoted methylene insertion into disulfide bonds has been achieved using acetone as a methylene source under mild conditions. This method provides a convenient and practical route to dithioacetals in up to 96% yield with good functional group compatibility. PMID- 29790545 TI - Heteroleptic samarium(iii) halide complexes probed by fluorescence-detected L3 edge X-ray absorption spectroscopy. AB - The addition of various oxidants to the near-linear Sm(ii) complex [Sm(N??)2] (1), where N?? is the bulky bis(triisopropylsilyl)amide ligand {N(SiiPr3)2}, afforded a family of heteroleptic three-coordinate Sm(iii) halide complexes, [Sm(N??)2(X)] (X = F, 2-F; Cl, 2-Cl; Br, 2-Br; I, 2-I). In addition, the trinuclear cluster [{Sm(N??)}3(MU2-I)3(MU3-I)2] (3), which formally contains one Sm(ii) and two Sm(iii) centres, was isolated during the synthesis of 2-I. Complexes 2-X are remarkably stable towards ligand redistribution, which is often a facile process for heteroleptic complexes of smaller monodentate ligands in lanthanide chemistry, including the related bis(trimethylsilyl)amide {N(SiMe3)2} (N''). Complexes 2-X and 3 have been characterised by single crystal X-ray diffraction, elemental analysis, multinuclear NMR, FTIR and electronic spectroscopy. The Lalpha1 fluorescence-detected X-ray absorption spectra recorded at the Sm L3-edge for 2-X exhibited a resolved pre-edge peak defined as an envelope of quadrupole-allowed 2p -> 4f transitions. The X-ray absorption spectral features were successfully reproduced using time-dependent density functional theoretical (TD-DFT) calculations that synergistically support the experimental observations as well as the theoretical model upon which the electronic structure and bonding in these lanthanide complexes is derived. PMID- 29790551 TI - A porous nickel cyclotetraphosphate nanosheet as a new acid-stable electrocatalyst for efficient hydrogen evolution. AB - The stability of non-precious metal-based electrocatalysts for the acidic hydrogen evolution reaction (HER) is of great importance. Here, we have used nickel cyclotetraphosphate (Ni2P4O12) nanosheet arrays as a HER electrocatalyst for the first time. The Ni2P4O12 arrays were obtained through a facile low temperature phosphorylation process and possess superior HER catalytic activities and stability in acid. The Ni2P4O12 delivers a small overpotential of 131.8 mV at -10 mA cm-2 and a low Tafel slope of 47.8 mV dec-1 in 0.5 M H2SO4, comparable to most of the non-precious metal-based catalysts. Importantly, the Ni2P4O12 shows a negligible potential change (6.5 mV) over 80 000 s continuous testing in acid. The remarkable catalytic performances of Ni2P4O12 are mainly attributed to the inductive effect of P4O124- and its polymer-like structure, promoting it as a potential acid-stable HER electrocatalyst. PMID- 29790552 TI - Quantum dot-polymer conjugates for stable luminescent displays. AB - The broad absorption of light in the UV-Vis-NIR region and the size-based tunable photoluminescence color of semiconductor quantum dots make these tiny crystals one of the most attractive antennae in solar cells and phosphors in electrooptical devices. One of the primary requirements for such real-world applications of quantum dots is their stable and uniform distribution in optically transparent matrices. In this work, we prepare transparent thin films of polymer-quantum dot conjugates, where CdSe/ZnS quantum dots are uniformly distributed at high densities in a chitosan-polystyrene copolymer (CS-g-PS) matrix. Here, quantum dots in an aqueous solution are conjugated to the copolymer by a phase transfer reaction. With the stable conjugation of quantum dots to the copolymer, we prevent undesired phase separation between the two and aggregation of quantum dots. Furthermore, the conjugate allows us to prepare transparent thin films in which quantum dots are uniformly distributed at high densities. The CS-g PS copolymer helps us in not only preserving the photoluminescence properties of quantum dots in the film but also rendering excellent photostability to quantum dots at the ensemble and single particle levels, making the conjugate a promising material for photoluminescence-based devices. PMID- 29790553 TI - XPS experimental and DFT investigations on solid solutions of Mo1-xRexS2 (0 < x < 0.20). AB - The synthesis, characterization, experimental X-ray photoelectron spectra (XPS) and density-functional theory (DFT) investigations on solid solutions of Mo1 xRexS2 (x = 0.05, 0.10, 0.15 and 0.20) are reported herein. It is shown that even at a low concentration of dopant Re atoms, clustering occurs. At an Re concentration of 5% the formation of dimer-like impregnations is observed. An increase in the dopant concentration leads to an increase in the amount of clustered rhenium atoms and to the formation of rhombic clusters. The absence of magnetism within the studied Mo1-xRexS2 solid solutions allowed us to suggest a mechanism for the distribution of rhenium inside molybdenum disulphide through the initial formation of rhenium disulphide and its subsequent spreading. PMID- 29790554 TI - Construction of dual-functional polymer nanomaterials with near-infrared fluorescence imaging and polymer prodrug by RAFT-mediated aqueous dispersion polymerization. AB - The performance of functional polymer nanomaterials is a vigorously discussed topic in polymer science. We devoted ourselves to investigating polymer nanomaterials based on near-infrared (NIR) fluorescence imaging and polymer prodrug in this study. Aza-boron dipyrromethene (BODIPY) is an important organic dye, having characteristics such as environmental resistance, light resistance, high molar extinction coefficient, and fluorescence quantum yield. We incorporated it into our target monomer, which can be polymerized without changing its parent structure in a polar solvent and copolymerized with water soluble monomer to improve the solubility of the dye in an aqueous solution. At the same time, the hydrophobic drug camptothecin (CPT) was designed as a prodrug monomer, and the polymeric nanoparticles (NPs) with NIR fluorescence imaging and prodrug were synthesized in situ in reversible addition-fragmentation chain transfer (RAFT)-mediated aqueous dispersion polymerization. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed the final uniform size of the dual-functional polymeric NPs morphology. The dual-functional polymeric NPs had a strong absorption and emission signal in the NIR region (>650 nm) based on the fluorescence tests. In consideration of the long-term biological toxicity, confocal laser scanning microscopy (CLSM) results indicated that the dual-functional NPs with controlled drug content exhibited effective capability of killing HeLa cells. In addition, in vivo imaging of the dual-functional NPs was observed in real time, and the fluorescent signals clearly demonstrated the dynamic process of prodrug transfer. PMID- 29790555 TI - Copper-catalyzed ambient-temperature decarboxylative annulation of isatins with amidine hydrochlorides: a facile access to 2-(1,3,5-triazin-2-yl)aniline derivatives. AB - A copper-catalyzed cascade reaction using isatins and amidine hydrochlorides for the synthesis of 2-(1,3,5-triazin-2-yl)aniline derivatives has been developed. This reaction features commercially available starting materials, mild reaction conditions and good functional group tolerance. PMID- 29790556 TI - Fabricating highly luminescent solid hybrids based on silicon nanoparticles: a simple, versatile and green method. AB - In this work, we report a simple but novel method to transfer highly luminescent silicon nanoparticles (Si NPs) from solutions to solids without sacrificing their excellent photoluminescence (PL) properties. Hybrid Si NP/clay phosphors that glowed ultrabright and had colorful PL properties were first obtained. More importantly, large-area and flexible films with superior PL properties can be easily obtained via combining the Si NP/clay hybrids with different kinds of polymer. The Si NP-based phosphors and films from our method show high stabilities with no significant loss of PL performance after long-term storage (several months). In addition, bright yellow-emitting Si NPs were prepared and used as down-converters for white-light-emitting diodes (W-LEDs). Overall, this work presents a simple, versatile and green method to fabricate Si NP-based solid hybrids with superior PL properties, which has promise to be applied in the future in solid-state lighting fields. PMID- 29790557 TI - Controlling the magic size of white light-emitting CdSe quantum dots. AB - White light-emitting quantum dots (QDs) have shown brilliant prospects as a white light source in solid-state lighting devices, however their commercial application is limited by their low fluorescence quantum yield (QY). Here, we report a facile thermal pyrolyzed organometallic route to synthesize white-light emitting CdSe QDs with enhanced QY, by employing a particular non-coordinating solvent and long carbon chain amine. By clarifying the three distinct growing stages of CdSe nanocrystals, we are able to determine the critical growth parameters for high quality magic size QDs. According to the optical measurement and advanced characterization result, the as-synthesized magic-size QD samples show an enhanced QY (up to 64%) and an ultra-high stability with no degradation even after 120 days, while the fabricated WLED devices also exhibit desirable properties (e.g., high QY and CRI, decent efficacy), demonstrating progress towards the desired efficiency of a commercially viable solid-state lighting device. PMID- 29790558 TI - Proteins as supramolecular hosts for C60: a true solution of C60 in water. AB - Hybrid systems have great potential for a wide range of applications in chemistry, physics and materials science. Conjugation of a biosystem to a molecular material can tune the properties of the components or give rise to new properties. As a workhorse, here we take a C60@lysozyme hybrid. We show that lysozyme recognizes and disperses fullerene in water. AFM, cryo-TEM and high resolution X-ray powder diffraction show that the C60 dispersion is monomolecular. The adduct is biocompatible, stable in physiological and technologically-relevant environments, and easy to store. Hybridization with lysozyme preserves the electrochemical properties of C60. EPR spin-trapping experiments show that the C60@lysozyme hybrid produces ROS following both type I and type II mechanisms. Due to the shielding effect of proteins, the adduct generates significant amounts of 1O2 also in aqueous solution. In the case of type I mechanism, the protein residues provide electrons and the hybrid does not require addition of external electron donors. The preparation process and the properties of C60@lysozyme are general and can be expected to be similar to other C60@protein systems. It is envisaged that the properties of the C60@protein hybrids will pave the way for a host of applications in nanomedicine, nanotechnology, and photocatalysis. PMID- 29790560 TI - Twin-mediated epitaxial growth of highly lattice-mismatched Cu/Ag core-shell nanowires. AB - Lattice-mismatch is an important factor for the heteroepitaxial growth of core shell nanostructures. A large lattice-mismatch usually leads to a non-coherent interface or a polycrystalline shell layer. In this study, a conformal Ag layer is coated on Cu nanowires with dense nanoscale twin boundaries through a galvanic replacement reaction. Despite a large lattice mismatch between Ag and Cu (~12.6%), the Ag shell replicates the twinning structure in Cu nanowires and grows epitaxially on the nanotwinned Cu nanowire. A twin-mediated growth mechanism is proposed to explain the epitaxy of high lattice-mismatch bimetallic systems in which the misfit dislocations are accommodated by coherent twin boundaries. PMID- 29790559 TI - PbTe quantum dots as electron transfer intermediates for the enhanced hydrogen evolution reaction of amorphous MoSx/TiO2 nanotube arrays. AB - Amorphous molybdenum sulfides (a-MoSx) have been demonstrated as economic and efficient hydrogen evolution catalysts for water splitting. Further improvements of their hydrogen evolution reaction (HER) activities could be achieved by coupling them with appropriate electron transfer intermediates via interfacial engineering. In this study, a novel ternary composite electrode comprising PbTe quantum dots (QDs), a-MoSx and TiO2 nanotube arrays (TNAs) was successfully fabricated by a facile combination of successive ionic layer adsorption and reaction (SILAR) and electrodeposition routes. Investigation of the microstructures and electrocatalytic properties of the a-MoSx/PbTe QD/TNA hybrid material show that PbTe QDs can work as electron temporary storage and electron transfer intermediates between the electrocatalyst a-MoSx and electrode-based material TiO2 that significantly lower the impedance of electrode process, enhance the energy band bending at the interface between the electrolyte and electrode surface, and increase the electrochemically active surface area. The electron interphase crossing from a-MoSx to electrolyte and electron transport inside the electrode are greatly strengthened. The ternary PbTe@MoSx/TNA electrode demonstrates lowered onset potential and Tafel slope and superior electrocatalytic activity and cyclic stability towards HER. PMID- 29790561 TI - Polymorphism of Ag29(BDT)12(TPP)43- cluster: interactions of secondary ligands and their effect on solid state luminescence. AB - We present the first example of polymorphism (cubic & trigonal) in single crystals of an atomically precise monolayer protected cluster, Ag29(BDT)12(TPP)43 . We demonstrate that C-Hpi interactions of the secondary ligands (TPP) are dominant in a cubic lattice compared to a trigonal lattice, resulting in a greater rigidity of the structure, which in turn, results in a higher luminescence efficiency in it. PMID- 29790562 TI - Deciphering ion concentration polarization-based electrokinetic molecular concentration at the micro-nanofluidic interface: theoretical limits and scaling laws. AB - The electrokinetic molecular concentration (EMC) effect at the micro-nanofluidic interface, which enables million-fold preconcentration of biomolecules, is one of the most compelling yet least understood nanofluidic phenomena. Despite the tremendous interests in EMC and the substantial efforts devoted, the detailed mechanism of EMC remains an enigma so far owing to its high complexity, which gives rise to the significant scientific controversies outstanding for over a decade and leaves the precise engineering of EMC devices infeasible. We report a series of experimental and theoretical new findings that decipher the mechanism of EMC. We demonstrate the first elucidation of two separate operating regimes of EMC, and establish the first theoretical model that analytically yet concisely describes the system. We further unveil the dramatically different scaling behaviors of EMC in the two regimes, thereby clarifying the long-lasting controversies. We believe this work represents important progress towards the scientific understanding of EMC and related nano-electrokinetic systems, and would enable the rational design and optimization of EMC devices for a variety of applications. PMID- 29790564 TI - Caged cyclopropenes for controlling bioorthogonal reactivity. AB - Bioorthogonal ligations have been designed and optimized to provide new experimental avenues for understanding biological systems. Generally, these optimizations have focused on improving reaction rates and orthogonality to both biology and other members of the bioorthogonal reaction repertoire. Less well explored are reactions that permit control of bioorthogonal reactivity in space and time. Here we describe a strategy that enables modular control of the cyclopropene-tetrazine ligation. We developed 3-N-substituted spirocyclopropenes that are designed to be unreactive towards 1,2,4,5-tetrazines when bulky N protecting groups sterically prohibit the tetrazine's approach, and reactive once the groups are removed. We describe the synthesis of 3-N spirocyclopropenes with an appended electron withdrawing group to promote stability. Modification of the cyclopropene 3-N with a bulky, light-cleavable caging group was effective at stifling its reaction with tetrazine, and the caged cyclopropene was resistant to reaction with biological nucleophiles. As expected, upon removal of the light labile group, the 3-N cyclopropene reacted with tetrazine to form the expected ligation product both in solution and on a tetrazine-modified protein. This reactivity caging strategy leverages the popular carbamate protecting group linkage, enabling the use of diverse caging groups to tailor the reaction's activation modality for specific applications. PMID- 29790563 TI - Backbone conformation affects duplex initiation and duplex propagation in hybridisation of synthetic H-bonding oligomers. AB - Synthetic oligomers equipped with complementary H-bond donor and acceptor side chains form multiply H-bonded duplexes in organic solvents. Comparison of the duplex forming properties of four families of oligomers with different backbones shows that formation of an extended duplex with three or four inter-strand H bonds is more challenging than formation of complexes that make only two H-bonds. The stabilities of 1 : 1 complexes formed between length complementary homo oligomers equipped with either phosphine oxide or phenol recognition modules were measured in toluene. When the backbone is very flexible (pentane-1,5-diyl thioether), the stability increases uniformly by an order of magnitude for each additional base-pair added to the duplex: the effective molarities for formation of the first intramolecular H-bond (duplex initiation) and subsequent intramolecular H-bonds (duplex propagation) are similar. This flexible system is compared with three more rigid backbones that are isomeric combinations of an aromatic ring and methylene groups. One of the rigid systems behaves in exactly the same way as the flexible backbone, but the other two do not. For these systems, the effective molarity for formation of the first intramolecular H-bond is the same as that found for the other two backbones, but additional H-bonds are not formed between the longer oligomers. The effective molarities are too low for duplex propagation in these systems, because the oligomer backbones cannot adopt conformations compatible with formation of an extended duplex. PMID- 29790565 TI - Positioning growth of NPB crystalline nanowires on the PTCDA nanocrystal template. AB - Non-planar organic molecules often form amorphous films via vapor phase deposition on surfaces. In this study, we demonstrate for the first time that direct crystalline growth of non-planar NPB is possible when the orientation of initially deposited molecules on a PTCDA nanocrystal template is controlled to make it analogous to the structure of the molecular crystal. The crystalline NPB nanowires can be further positioned by controlling the site-selective growth of PTCDA nanocrystal templates at pre-determined locations. Short channel bottom contact OFET array with the NPB nanowires directly grown on electrodes were subsequently fabricated. The hole mobility of NPB nanowires is improved by 40 fold in comparison to that of the amorphous films. PMID- 29790566 TI - Night shift work and breast cancer risk: what do the meta-analyses tell us? AB - Objectives This paper aims to compare results, assess the quality, and discuss the implications of recently published meta-analyses of night shift work and breast cancer risk. Methods A comprehensive search was conducted for meta analyses published from 2007-2017 that included at least one pooled effect size (ES) for breast cancer associated with any night shift work exposure metric and were accompanied by a systematic literature review. Pooled ES from each meta analysis were ascertained with a focus on ever/never exposure associations. Assessments of heterogeneity and publication bias were also extracted. The AMSTAR 2 checklist was used to evaluate quality. Results Seven meta-analyses, published from 2013-2016, collectively included 30 cohort and case-control studies spanning 1996-2016. Five meta-analyses reported pooled ES for ever/never night shift work exposure; these ranged from 0.99 [95% confidence interval (CI) 0.95-1.03, N=10 cohort studies) to 1.40 (95% CI 1.13-1.73, N=9 high quality studies). Estimates for duration, frequency, and cumulative night shift work exposure were scant and mostly not statistically significant. Meta-analyses of cohort, Asian, and more fully-adjusted studies generally resulted in lower pooled ES than case-control, European, American, or minimally-adjusted studies. Most reported statistically significant between-study heterogeneity. Publication bias was not evident in any of the meta-analyses. Only one meta-analysis was strong in critical quality domains. Conclusions Fairly consistent elevated pooled ES were found for ever/never night shift work and breast cancer risk, but results for other shift work exposure metrics were inconclusive. Future evaluations of shift work should incorporate high quality meta-analyses that better appraise individual study quality. PMID- 29790567 TI - Regional diversity in the murine cortical vascular network is revealed by synchrotron X-ray tomography and is amplified with age. AB - Cortical bone is permeated by a system of pores, occupied by the blood supply and osteocytes. With ageing, bone mass reduction and disruption of the microstructure are associated with reduced vascular supply. Insight into the regulation of the blood supply to the bone could enhance the understanding of bone strength determinants and fracture healing. Using synchrotron radiation-based computed tomography, the distribution of vascular canals and osteocyte lacunae was assessed in murine cortical bone and the influence of age on these parameters was investigated. The tibiofibular junction from 15-week- and 10-month-old female C57BL/6J mice were imaged post-mortem. Vascular canals and three-dimensional spatial relationships between osteocyte lacunae and bone surfaces were computed for both age groups. At 15 weeks, the posterior region of the tibiofibular junction had a higher vascular canal volume density than the anterior, lateral and medial regions. Intracortical vascular networks in anterior and posterior regions were also different, with connectedness in the posterior higher than the anterior at 15 weeks. By 10 months, cortices were thinner, with cortical area fraction and vascular density reduced, but only in the posterior cortex. This provided the first evidence of age-related effects on murine bone porosity due to the location of the intracortical vasculature. Targeting the vasculature to modulate bone porosity could provide an effective way to treat degenerative bone diseases, such as osteoporosis. PMID- 29790568 TI - [Social cognition and cognitive functions in patients with epilepsy treated with eslicarbazepine acetate]. AB - INTRODUCTION: Epilepsy is accompanied by cognitive disorders, frequently aggravated by the use of antiepileptic drugs, which can affect social empathy. AIM: To analyse the impact of treatment with eslicarbazepine acetate (ESL) on social cognition and prefrontal cognitive functions in adults with focal epilepsy. PATIENTS AND METHODS: We conducted a prospective single-centre study with patients aged between 18 and 65 years with focal seizures treated with ESL. The patients were evaluated in their baseline visit and at six months after starting ESL treatment by means of tasks designed for theory of mind, executive and attentional functions, auditory-verbal memory, quality of life, and anxiety and depression. RESULTS: Forty-one patients were treated with ESL, and 30 completed the follow-up. A significant improvement was observed in the theory of mind tasks. In the analysis stratified by sex, the men showed greater improvement. A cognitive improvement was observed in the Wisconsin Card Sorting Test, Symbol Digit, Backward Digit Span and Stroop tests. No differences were found in the Quality of Life in Epilepsy-31 Inventory or in the Hospital Anxiety and Depression Scale. These results were independent of the reduction in the number of seizures and the ESL dosage. CONCLUSION: Treatment with ESL could improve some aspects of theory of mind in patients with epilepsy, especially in men and independently of the control of seizures, with no changes in quality of life, anxiety or depression. PMID- 29790569 TI - [Laryngeal dystonia: novel forms of therapeutic administration of botulinum toxin by direct routes]. AB - AIM: To describe our experience in the treatment of laryngeal dystonia (in abduction and adduction), with special emphasis given to the technical aspects (approach procedure, dosage and type of botulinum toxin type A used), as well as treatment response and possible side effects. PATIENTS AND METHODS: We conducted a cross-sectional descriptive study of a sample of patients with laryngeal dystonia treated by means of transoral administration of onabotulinumtoxinA or incobotulinumtoxinA over a period of 10 years (2007-2017). Data collected include demographic and clinical variables, treatment response (based on a self-rating scale), the duration of treatment and the appearance of side effects. RESULTS: SAMPLE SIZE: 15 patients (11 women; mean age: 44.06 years) with laryngeal dystonia (mean time since onset of 40 months; 12 patients with dystonia in adduction) and 174 administrations (92% incobotulinumtoxinA; average dosage of 5 U in each vocal cord). The procedure took an average of 11.7 minutes to perform. Response was good in 31% of the procedures and very good in 57.5%. Side effects were recorded in 14.4% of the procedures, although always mild and transitory, with a predominance of dysphagia and dysphonia. CONCLUSION: In our experience, transoral administration of botulinum toxin type A to treat laryngeal dystonia has proved to be a simple, quick, effective and safe technique. PMID- 29790570 TI - ["Man-in-the-barrel" syndrome: atypical manifestation of giant cell arteritis]. AB - INTRODUCTION: "Man-in-the-barrel" syndrome refers to diplegia of the upper extremities in which mobility of the head and lower limbs is preserved. Brachial plexitis that presents as "man-in-the-barrel" syndrome is an unusual manifestation of giant cell arteritis. We report a case of C5-C6 plexitis as part of the clinical features of a patient with giant cell arteritis. CASE REPORT: A 70-year-old male with a two-month history of weight loss, headache, facial pain and jaw claudication, associated with a persistent elevation of acute phase reactants and bilateral brachial plexopathy, with no evidence of neck or brain injuries or occult neoplasm and with negative autoimmunity tests. Results of the biopsy study of the temporal artery were compatible with giant cell arteritis, and the positron emission tomography scan revealed extensive vascular involvement of the aorta and its branches. CONCLUSIONS: Although the typical clinical manifestations of giant cell arteritis are headache, jaw claudication, loss of sight, constitutional symptoms and polymyalgia rheumatica, its presence must be suspected in patients over the age of 50 who manifest alterations affecting the peripheral nerve, including brachial diplegia with no other demonstrable cause. PMID- 29790571 TI - [Epidemiology of Alzheimer's disease and other dementias]. AB - INTRODUCTION: Dementia is a clinical syndrome resulting from a number of causations and which is usually accompanied by progressive and diffuse brain dysfunction. The different subtypes are characterised by a clinical picture with common symptoms that differ in terms of their aetiology, age, clinical presentation, clinical course and associated disorders. AIM: To present an update on the information available about the descriptive epidemiology of dementia and its main subtypes. DEVELOPMENT: The main data on prevalence, incidence and mortality were extracted from a literature review. Alzheimer's disease is the most frequent subtype and accounts for 60-80% of all the cases, followed by vascular dementia and other neurodegenerative dementias, such as dementia due to Lewy bodies, the dementia-Parkinson complex and frontotemporal dementia. Other subtypes of dementias present frequencies below 1%, and the epidemiological indicators available are not very robust. CONCLUSIONS: The prevalence and incidence of dementia increase exponentially from the age of 65 onwards. As a consequence of the progressive ageing of the population and the increase in life expectancy, the number of cases of dementia will rise in the coming decades. Recent studies point to a slight drop in the accumulated risk of dementia adjusted by age groups and sex over the last few decades in some countries. It is possible that by means of primary prevention strategies implemented upon the known risk factors for dementia the burden of dementia on public health will diminish in the future. PMID- 29790572 TI - [Selective dorsal rhizotomy: a review of the literature on this technique for the treatment of spasticity in infantile cerebral palsy]. AB - INTRODUCTION: Infantile cerebral palsy is a well-known condition, the prevalence of which has varied only slightly over the years. The most common subtype is spastic diplegia, and spasticity is the most disabling symptom. Its treatment involves a multidisciplinary intervention that includes rehabilitation, the use of drugs, and orthopaedic and nervous system surgery, where selective dorsal rhizotomy is a prominent procedure. AIM: To present a thorough review of the use, indication and long-term consequences of selective dorsal rhizotomy. DEVELOPMENT: It is a minimally invasive procedure aimed at reducing spasticity in the lower extremities in order to improve the ability to walk, lessen pain, facilitate care in everyday life and diminish the need for orthopaedic surgery. The literature contains a wide range of criteria for its use, and the main indication is spastic diplegia with the absence of dystonia. It is routinely performed in several countries, while we have no evidence of its application in ours. CONCLUSIONS: Following the literature review, we believe there is enough experience to state that selective dorsal rhizotomy is a safe and simple technique from which many patients with spasticity of the lower limbs secondary to infantile cerebral palsy can benefit in both the short and the long term. PMID- 29790573 TI - [Vitiligo with Koebner phenomenon in a patient with multiple sclerosis treated with alemtuzumab]. PMID- 29790574 TI - Investigations on VELVET regulatory mutants confirm the role of host tissue acidification and secretion of proteins in the pathogenesis of Botrytis cinerea. AB - The Botrytis cinerea VELVET complex regulates light-dependent development and virulence. The goal of this study was to identify common virulence defects of several VELVET mutants and to reveal their molecular basis. Growth, differentiation, physiology, gene expression and infection of fungal strains were analyzed, and quantitative comparisons of in planta transcriptomes and secretomes were performed. VELVET mutants showed reduced release of citric acid, the major acid secreted by the wild-type, whereas no significant role for oxalic acid was observed. Furthermore, a common set of infection-related and secreted proteins was strongly underexpressed in the mutants. Quantitative secretome analysis with 15 N metabolic labeling revealed a correlation of changes in protein and mRNA levels between wild-type and mutants, indicating that transcript levels determine the abundance of secreted proteins. Infection sites kept at low pH partially restored lesion expansion and expression of virulence genes by the mutants. Drastic downregulation of proteases in the mutants was correlated with incomplete degradation of cellular host proteins at the infection site, but no evidence was obtained that aspartyl proteases are required for lesion formation. The B. cinerea VELVET complex controls pathogenic differentiation by regulating organic acid secretion, host tissue acidification, gene expression and protein secretion. PMID- 29790575 TI - First identification of the nervous necrosis virus isolated from cultured golden pompano (Trachinotus ovatus) in Guangxi, China. PMID- 29790576 TI - Memory T cell subsets in healthy gingiva and periodontitis tissues. AB - BACKGROUND: In the gingival sulcus, effective and balanced innate and adaptive immune responses against subgingival plaque microbiome are crucial to maintain immune homeostasis. In this study, we investigated the memory T cell subsets in healthy gingiva and periodontitis tissues. METHODS: Anatomical localization of T cells (CD3+ , CD4+ , and CD8+ ) in healthy gingiva and periodontitis tissues were examined immunohistochemically. Subsets of memory T cells from isolated gingival cells were analyzed by flow cytometry using a cocktail of monoclonal antibodies (anti-CD69, anti-CD103, anti-CD45RA, anti-CCR7, anti-CD28, and anti-CD95). Intracellular cytokine staining of interleukin (IL)-17 and interferon (IFN)-gamma expression on memory T cells in periodontitis tissues was also investigated. RESULTS: We found that healthy gingiva contains two memory T cell populations; a CD69- recirculating population and a CD69+ gingiva-resident memory T cell population. CD4+ T cells with transitional memory (TTM ) phenotype (CD45RA- CCR7- CD28+ CD95+ ) constitute the major subset within these two populations. A significant increase in the proportion of CD4+ CD69+ CD103- memory T cells was observed in periodontitis tissues compared with healthy gingiva. CD4+ memory T cells from periodontitis tissues produced either IL-17 or IFN-gamma whereas CD8+ memory T cells produced only IFN-gamma. CONCLUSIONS: Our findings suggest that recirculating and gingiva-resident memory T cells could represent an important part of the immune surveillance network in the connective tissue, maintaining periodontal homeostasis. Imbalance of subgingival bacterial communities could damage gingival barrier allowing bacterial antigens to get access to the deeper connective tissue where they activate memory T cells leading to deleterious inflammation; a hallmark of periodontitis. PMID- 29790578 TI - Mycorrhizal fungi affect orchid distribution and population dynamics. AB - Symbioses are ubiquitous in nature and influence individual plants and populations. Orchids have life history stages that depend fully or partially on fungi for carbon and other essential resources. As a result, orchid populations depend on the distribution of orchid mycorrhizal fungi (OMFs). We focused on evidence that local-scale distribution and population dynamics of orchids can be limited by the patchy distribution and abundance of OMFs, after an update of an earlier review confirmed that orchids are rarely limited by OMF distribution at geographic scales. Recent evidence points to a relationship between OMF abundance and orchid density and dormancy, which results in apparent density differences. Orchids were more abundant, less likely to enter dormancy, and more likely to re emerge when OMF were abundant. We highlight the need for additional studies on OMF quantity, more emphasis on tropical species, and development and application of next-generation sequencing techniques to quantify OMF abundance in substrates and determine their function in association with orchids. Research is also needed to distinguish between OMFs and endophytic fungi and to determine the function of nonmycorrhizal endophytes in orchid roots. These studies will be especially important if we are to link orchids and OMFs in efforts to inform conservation. PMID- 29790579 TI - Extrathoracic subclavian-axillary vein location and morphological features over the first rib for pacemaker and defibrillator lead implantation. AB - BACKGROUND: We aimed to describe the variations of extrathoracic subclavian axillary vein location and its morphology over the first rib by venography in order to facilitate venous puncture using fluoroscopic landmarks without contrast venography, and evaluate the success rate of punctures, which is made with our method. METHODS: Patients who had undergone de novo lead implantation with the help of prepuncture venography between 2011 and 2015 were enrolled. For detection of the segmental location of the axillary vein, the zones were defined (Zone 1: Posterior, Zone 2: Lateral, Zone 3: Medial) at the first rib by fluoroscopy. Additionally, patients, who underwent venous puncture with our method after January 2017, were evaluated in terms of puncture success. RESULTS: Four hundred thirty-three patients who had prepuncture contrast venography for defibrillator or pacemaker lead implantation in 2011-2015 were analyzed. The most common position of the axillary vein was found to be over zone 2 (91%) while the zone 1 location was 8.5% and the zone 3 was 0.5%. Venous valves were detected on the first rib in 98 patients. After January 2017, venous puncture using fluoroscopic landmarks was performed to 171 patients. The punctures were successfully performed over zone 2 with our method in 90.7% of the patients. CONCLUSIONS: The most common radioanatomic position of the extrathoracic subclavian-axillary vein was observed at zone 2 according to our method and the probability of presence of venous valve over the first rib is 22%. Additionally, the success rate of puncture using fluoroscopic landmarks over zone 2 was 90.7%. PMID- 29790577 TI - Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis. AB - BACKGROUND: Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. METHODS: This case-control study included pediatric subjects with EoE (>=15 eosinophils/HPF) and non-EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1-IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. RESULTS: Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2 mg/g protein [interquartile range: 1.0-13.1 mg/g protein] vs 0.2 mg/g protein [0.1-0.9]; P < .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P = .0006); histologic grade (P = .0011) and stage (P = .0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. CONCLUSION: These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally. PMID- 29790580 TI - Preclinical evaluation of potential infection-imaging probe [68 Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation. AB - The development of bacteria-specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10 tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA) conjugated peptide [68 Ga]Ga-DOTA-K-A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68 Ga]Ga-DOTA-K-A9 synthesis omitting the use of acetone was developed, yielding 93 +/- 0.9% radiochemical purity. The in vivo infection binding specificity of [68 Ga]Ga-DOTA-K-A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine-induced inflammation and compared with 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG). The scans showed that [68 Ga]Ga-DOTA-K-A9 accumulated in all the infected mice at injected doses >=3.6 MBq. However, the tracer was not found to be selective towards infection, since the [68 Ga]Ga-DOTA-K-A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5 carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA-K A9, the microscopy results suggested that TAMRA-K-A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [68 Ga]Ga DOTA-K-A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria. PMID- 29790581 TI - The pharmacokinetics, pharmacodynamics and tolerability of PUR0200, a novel tiotropium formulation, in chronic obstructive pulmonary disease. AB - AIMS: PUR0200 is a tiotropium bromide formulation engineered with the iSPERSE dry powder delivery technology. PUR0200 is being developed as a bioequivalent alternative to tiotropium bromide, delivered using Spiriva(r) HandiHaler(r) (HH). We investigated the bronchodilator effects, pharmacokinetics and safety of PUR0200 in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, placebo-controlled, crossover study using different PUR0200 doses and the comparator tiotropium HH. In vitro aerodynamic particle size distribution (aPSD) characterization of PUR0200 and tiotropium HH are presented. The main endpoints included forced expiratory volume in 1 s (FEV1 ) trough and (0-24 h) and pharmacokinetic parameters. RESULTS: The increased fine particle fraction of PUR0200 demonstrated by testing using the next-generation impactor increased the proportion of drug available for lung deposition compared with the tiotropium HH. There was a numerical dose-response effect for PUR0200 on FEV1 , with 3 MUg demonstrating a lower effect than higher doses. The placebo adjusted mean (95% confidence interval) increases from baseline at 24 h postdose were 150 ml (100-200), 210 ml (160-270) and 200 ml (140-250) for 3 MUg, 6 MUg and 9 MUg doses of PUR0200, respectively. Tiotropium HH (18 MUg) caused a mean 169 ml (standard deviation 157ml) improvement in trough FEV1 , which was not significantly different to the PUR0200 effects at any of the tested doses. CONCLUSIONS: PUR0200 treatment caused bronchodilation in COPD patients that was similar in magnitude to that caused by tiotropium HH. This enabled a similar clinical effect on lung function to be achieved with PUR0200 using a lower metered dose of tiotropium compared with tiotropium HH. PMID- 29790583 TI - Stress in biological invasions: Introduced invasive grey squirrels increase physiological stress in native Eurasian red squirrels. AB - Invasive alien species can cause extinction of native species through processes including predation, interspecific competition for resources or disease-mediated competition. Increases in stress hormones in vertebrates may be associated with these processes and contribute to the decline in survival or reproduction of the native species. Eurasian red squirrels (Sciurus vulgaris) have gone extinct across much of the British Isles and parts of Northern Italy following the introduction of North American invasive grey squirrels (Sciurus carolinensis). We extracted glucocorticoid metabolites from faecal samples to measure whether the presence of the invasive species causes an increase in physiological stress in individuals of the native species. We show that native red squirrels in seven sites where they co-occurred with invasive grey squirrels had glucocorticoid concentrations that were three times higher than those in five sites without the invasive species. Moreover, in a longitudinal study, stress hormones in native red squirrels increased after colonisation by grey squirrels. When we experimentally reduced the abundance of the invasive grey squirrels, the concentration of faecal glucocorticoid metabolites in co-occurring red squirrels decreased significantly between pre- and postremoval periods. Hence, we found that the invasive species acts as a stressor which significantly increases the concentrations of glucocorticoids in the native species. Given that sustained elevations in glucocorticoids could reduce body growth and reproductive rate, our results are consistent with previous studies where the co-occurrence of the invasive grey squirrel was associated with smaller size and lower reproductive output in red squirrels. PMID- 29790584 TI - Effects of Psidium guajava leaf extract on secretion systems of Gram-negative enteropathogenic bacteria. AB - We screened a total of 672 plant-tissue extracts to search for phytochemicals that inhibit the function of the type III secretion system (T3SS) of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). Among candidates examined, we found that an extract from the leaves of Psidium guajava (guava) inhibited the secretion of the EspB protein from EPEC and EHEC without affecting bacterial growth. The guava extract (GE) also inhibited EPEC and EHEC from adhering to and injecting EspB protein into HEp-2 cells. GE seemed to block the translocation of EspB from the bacterial cells to the culture medium. In addition to EPEC and EHEC, GE also inhibited the T3SS of Yersinia pseudotuberculosis and Salmonella enterica serovar Typhimurium. After exposure to GE, Y. pseudotuberculosis stopped the secretion of Yop proteins and lost its ability to induce the apoptosis of mouse bone marrow-derived macrophages. S. Typhimurium exposed to GE ceased the secretion of Sip proteins and lost its ability to invade HEp-2 cells. GE inhibited EspC secretion, the type V secretion protein of EPEC, but not Shiga toxin2 from EHEC. Thus, our results suggest that guava leaves contain a novel type of antimicrobial compound that could be used for the therapeutic treatment and prevention of gram-negative enteropathogenic bacterial infections. PMID- 29790585 TI - The intracellular nucleotide-binding leucine-rich repeat receptor (SlNRC4a) enhances immune signalling elicited by extracellular perception. AB - Plant recognition and defence against pathogens employs a two-tiered perception system. Surface-localized pattern recognition receptors (PRRs) act to recognize microbial features, whereas intracellular nucleotide-binding leucine-rich repeat receptors (NLRs) directly or indirectly recognize pathogen effectors inside host cells. Employing the tomato PRR LeEIX2/EIX model system, we explored the molecular mechanism of signalling pathways. We identified an NLR that can associate with LeEIX2, termed SlNRC4a (NB-LRR required for hypersensitive response-associated cell death-4). Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defence responses, whereas silencing SlNRC4 reduces plant immunity. Moreover, the coiled-coil domain of SlNRC4a is able to associate with LeEIX2 and is sufficient to enhance responses upon EIX perception. On the basis of these findings, we propose that SlNRC4a acts as a noncanonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perceptions. PMID- 29790582 TI - Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents. AB - Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for nonalcoholic fatty liver disease (NAFLD) through simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the effect of a liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels, and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose-fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet-induced hepatic steatosis, protein kinase C epsilon activation, and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (approximately 30% to 130%, depending on the length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to approximately a 15% increase in hepatic very low-density lipoprotein production and approximately a 20% reduction in triglyceride clearance by lipoprotein lipase (P <= 0.05). At the molecular level, these changes were associated with increases in liver X receptor/sterol response element-binding protein-1 and decreases in peroxisome proliferator-activated receptor-alpha target activation and could be reversed with fenofibrate co treatment in a high-fat diet mouse model. Conclusion: Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. PMID- 29790587 TI - Prevalence of Venous Thromboembolism Diagnosed in Emergency Department Visits by Cancer Patients and Associated Healthcare Resource Utilization in the United States. PMID- 29790586 TI - Pharmacokinetic and pharmacodynamic model for analysis of adalimumab administered for Crohn's disease. AB - Adalimumab (ADA) is used as a therapeutic agent for Crohn's disease (CD). Although the dosage regimen has been established through clinical trial experience, it has not been analysed theoretically. The present study analysed of sequential changes in the Crohn's disease activity index (CDAI) after repeated administrations of adalimumab using a pharmacokinetic and pharmacodynamic model. In addition, we analysed the validity of the dosage regimen, and the potential efficacy gained by increasing the dose and reducing the interval of administration. The sequential changes in CDAI values obtained with our model were in good agreement with observed CDAI values, which is considered to show the validity of our analysis. We consider that our results showed the importance of a loading dose of adalimumab to obtain remission in an early stage of active CD. In addition, we showed that patients who have an incomplete response to adalimumab can obtain similar efficacy from increasing the dose and reducing the dose interval. In conclusion, our results showed that the present model may be applied to predict the CDAI values of adalimumab for CD. They indicate the validity of the dosage regimen, as well as the efficacy of increasing the dose and reducing the dose interval. PMID- 29790588 TI - The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling. AB - The identification of viability-associated long noncoding RNAs (lncRNAs) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied an RNA interference screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected cancer susceptibility 9 (CASC9) due to the strength of its phenotype, expression, and up regulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by clustered regularly interspaced short palindromic repeats interference and single small interfering RNA (siRNA)-mediated and siRNA pool-mediated depletion of CASC9. Further, CASC9 depletion caused an increase in apoptosis and a decrease of proliferation. We identified the RNA binding protein heterogeneous nuclear ribonucleoprotein L (HNRNPL) as a CASC9 interacting protein by RNA affinity purification and validated it by native RNA immunoprecipitation. Knockdown of HNRNPL mimicked the loss-of-viability phenotype observed upon CASC9 depletion. Analysis of the proteome (stable isotope labeling with amino acids in cell culture) of CASC9-depleted and HNRNPL-depleted cells revealed a set of coregulated genes which implied a role of the CASC9:HNRNPL complex in AKT signaling and DNA damage sensing. CASC9 expression levels were elevated in patient-derived tumor samples compared to normal control tissue and had a significant association with overall survival of HCC patients. In a xenograft chicken chorioallantoic membrane model, we measured decreased tumor size after knockdown of CASC9. Conclusion: Taken together, we provide a comprehensive list of viability-associated lncRNAs in HCC; we identified the CASC9:HNRNPL complex as a clinically relevant viability-associated lncRNA/protein complex which affects AKT signaling and DNA damage sensing in HCC. PMID- 29790589 TI - Genotype-Phenotype Correlation of Hereditary Erythrocytosis Mutations, a single center experience. AB - Hereditary erythrocytosis is associated with high oxygen affinity hemoglobin variants (HOAs), 2,3-bisphosphoglycerate deficiency and abnormalities in EPOR and the oxygen-sensing pathway proteins PHD, HIF2alpha, and VHL. Our laboratory has 40 years of experience with hemoglobin disorder testing and we have characterized HOAs using varied protein and molecular techniques including functional assessment by p50 analysis. In addition, we have more recently commenced adding the assessment of clinically relevant regions of the VHL, BPGM, EPOR, EGLN1 (PHD2), and EPAS1 (HIF2A) genes in a more comprehensive hereditary erythrocytosis panel of tests. Review of our experience confirms a wide spectrum of alterations associated with erythrocytosis which we have correlated with phenotypic and clinical features. Through generic hemoglobinopathy testing we have identified 762 patients with 81 distinct HOA Hb variants (61 beta, 20 alpha), including 12 that were first identified by our laboratory. Of the 1192 cases received for an evaluation specific for hereditary erythrocytosis, approximately 12% had reportable alterations: 85 pathogenic/likely pathogenic mutations and 58 variants of unknown significance. Many have not been previously reported. Correlation with clinical and phenotypic data supports an algorithmic approach to guide economical evaluation; although, testing is expanded if the suspected causes are negative or of uncertain significance. Clinical features are similar and range from asymptomatic to recurrent headaches, fatigue, restless legs, chest pain, exertional dyspnea and thrombotic episodes. Many patients were chronically phlebotomized with reported relief of symptoms. This article is protected by copyright. All rights reserved. PMID- 29790590 TI - Evaluation of biofilm removal and adverse effects on acrylic resin by diluted concentrations of sodium hypochlorite and Ricinus communis solutions. AB - PURPOSE: To verify whether 0.1% and 0.2% sodium hypochlorite (NaOCl), and 8% Ricinus communis (RC) were able to remove denture biofilm without causing deleterious effects to acrylic resin. BACKGROUND: Previous data show that denture cleansers are effective in reducing biofilm; however, they can change acrylic resin properties. METHODS: In a crossover trial, 47 denture wearers brushed and soaked their dentures (20 min/14 d): control, 0.85% saline; SH1, 0.1% NaOCl; SH2, 0.2% NaOCl and RC. Denture biofilm on the intaglio surface was stained, photographed and quantified (Image Tool(r) ). Furthermore, 80 rectangular and 80 disc-shaped specimens (Lucitone 550) were assigned into tested solutions (n = 20), simulating 5 years of daily short immersions (20 minutes). A colorimeter and the National Bureau of Standards units (NBS) determined colour data (DeltaE). Surface roughness and flexural strength were measured using rugosimeter and universal testing machine, respectively. Data were compared by the Friedman test (alpha = .05) followed by Wilcoxon, corrected by Bonferroni (alpha = .005) (clinical) and Kruskal-Wallis followed by the Dunn test (alpha = .05) (laboratorial). RESULTS: SH2 (MR=1.77) showed lower biofilm coverage; SH1 (MR = 2.37) and RC (MR = 2.74) presented intermediated values. RC (1.10 [0.96:1.75]) revealed higher colour alteration than SH1 (0.71 [0.62:0.80]) and SH2 (0.74 [0.58:0.85]); however, NBS classified all solutions as "trace" (0.0-0.5). There was no statistical significance for surface roughness (P = .760) and flexural strength (P = .547). CONCLUSIONS: The 0.2% NaOCl showed the best clinical performance and did not cause adverse effects on acrylic resin on laboratory analyses. PMID- 29790591 TI - Synthesis of 13 C6 -labeled, dual-target inhibitor of cannabinoid-1 receptor (CB1 R) and inducible nitric oxide synthase (iNOS). AB - Cannabinoid-1 receptor (CB1 R) antagonists/inverse agonists have great potential in the treatment of metabolic disorders like dyslipidemia, type 2 diabetes, and nonalcoholic steatohepatitis. Cannabinoid-1 receptor inverse agonists have also been reported to be effective in mitigating fibrotic disorders in murine models. Inducible nitric oxide synthase is another promising target implicated in fibrotic and inflammatory disorders. We have disclosed MRI-1867 as a potent and selective, peripherally acting dual-target inhibitor of the CB1 R and inducible nitric oxide synthase (iNOS). Herein, we report the synthesis of [13 C6 ]-MRI 1867 as a racemate from commercially available chlorobenzene-13 C6 as the starting, stable-isotope label reagent. The racemic [13 C6 ]-MRI-1867 was further processed to the stable-isotope-labeled enantiopure compounds using chiral chromatography. Both racemic [13 C6 ]-MRI-1867 and S-13 C6 -MRI-1867 will be used to quantitate unlabeled S-MRI-1867 during clinical drug metabolism and pharmacokinetics studies and will be used as a liquid chromatography-tandem mass spectrometry bioanalytical standard. PMID- 29790592 TI - Hepatitis B Virus-Upregulated LNC-HUR1 Promotes Cell Proliferation and Tumorigenesis by Blocking p53 Activity. AB - Recent studies have indicated that a number of long noncoding RNAs (lncRNAs) are dysregulated in hepatocellular carcinoma, while their aberrant expressions are associated with tumorigenesis and poor prognosis. To identify hepatitis B virus (HBV)-related lncRNAs, we used RNA deep sequencing to quantify the abundances of lncRNAs in HepG2 cells and HBV transgenic HepG2-4D14 cells. Here, we demonstrate that lnc-HUR1 is significantly upregulated in HepG2-4D14 cells. We found that HBV encoded hepatitis B x protein can enhance the transcription of lnc-HUR1. Overexpression of lnc-HUR1 promotes cell proliferation, whereas knockdown of lnc HUR1 inhibits cell growth. We identified that lnc-HUR1 can interact with p53 and inhibit its transcriptional regulation on downstream genes, such as p21 and B cell lymphoma 2-associated X protein. We generated lnc-HUR1 transgenic mice and performed the partial hepatectomy (PHx) to examine liver regeneration. The data showed that the ratio of liver weight to body weight in lnc-HUR1 transgenic mice is higher than that in wild-type (WT) littermates at day 2 and day 3 following hepatectomy. Consistently, the results of bromodeoxyuridine staining on liver sections following hepatectomy indicate that the ratio of bromodeoxyuridine positive cells in lnc-HUR1 transgenic mice is significantly higher than that in WT mice, suggesting that lnc-HUR1 promotes cell proliferation during liver regeneration. Next, we performed the experiment of diethylnitrosamine-induced tumorigenesis. The data demonstrate that tumor number in lnc-HUR1 transgenic mice is higher compared with control mice, indicating that lnc-HUR1 enhances diethylnitrosamine-induced tumorigenesis. Conclusion: We reveal that HBV upregulated lnc-HUR1 promotes cell proliferation and tumorigenesis by interacting with p53 to block downstream gene transcription. Our findings suggest that lnc HUR1 plays an important role in HBV-related hepatocellular carcinoma development and may serve as a therapeutic marker for hepatocellular carcinoma. (Hepatology 2018; 00:000-000). PMID- 29790593 TI - Efficacy and absorption of topical sirolimus for the treatment of vascular anomalies in children: A case series. AB - BACKGROUND/OBJECTIVES: Efficacy of topical sirolimus has recently been described in lymphatic anomalies but not in other types of vascular anomalies. To our knowledge, systemic absorption of topical sirolimus in these lesions has not yet been reported. The objective was to evaluate the efficacy, tolerance, and absorption of topical sirolimus 0.1% with different types of vascular anomalies in children. METHODS: Sirolimus 0.1% was applied on cutaneous vascular anomalies in six children aged 2-17. These anomalies consisted of three extratruncular micro- and macrocystic lymphatic malformations and one each verrucous venous malformation, truncular lymphatic malformation with angiokeratomas, and infantile hemangioma. Sirolimus blood levels were measured after 1 week, 1 month, and 3 months. RESULTS: A rapid decrease in the size of superficial lymphatic malformations in three of six patients and a significant decrease in discharge from oozing lesions were observed. Response occurred in less than 3 months. The truncular lymphatic malformation, verrucous venous malformation, and infantile hemangioma did not respond to topical sirolimus. Sirolimus levels were undetectable. Adverse effects were limited to local irritation. CONCLUSIONS: Topical sirolimus 0.1% is a useful treatment for cutaneous manifestations of extratruncular lymphatic malformations. The only adverse effect is local irritation. No systemic effects are expected, because blood levels are clinically insignificant. PMID- 29790594 TI - Barriers to and enablers of diabetic retinopathy screening attendance: a systematic review of published and grey literature. AB - AIMS: To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance. METHODS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance. RESULTS: Sixty-nine primary studies were included. We identified six theoretical domains ['environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (51%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers. CONCLUSIONS: Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance. PMID- 29790595 TI - Monetary and nonmonetary household consumption of health services and the role of insurance benefits: An analysis of the Mexico's National Household Income and Expenditure Survey. AB - OBJECTIVES: To study the monetary and nonmonetary consumption of healthcare services at household level in Mexico and the magnitude of the contribution of public programs. METHODS: By using the National Household Income and Expenditure Survey 2012, we performed a cross-sectional and observational analysis of actual household consumption of health services by insurance type (no insurance, social security, Seguro Popular (SP)). Household consumption was divided into 2 categories: consumption related to "monetary" expenditure in health care and "nonmonetary" consumption in health care by the household. Nonmonetary included self-consumption or gifts received from other households and institutional contributions such as government payments or private organization transfers. RESULTS: In SP households, monetary and nonmonetary consumption of health services represented the highest proportion of available household expenditure (11.2%) compared to uninsured (8.4%) and social security (5.9%) households. The prevalence of outpatient consultation and medicine use is the highest among the health service consumption categories regardless of insurance status. Distribution of nonmonetary versus monetary consumption of health services was pro-poor: The poorer the households, the larger the proportion of nonmonetary consumption. CONCLUSIONS: The higher probability of receiving nonmonetary resources as a component of health service consumption in SP households is likely to increase the affordability to health services and likely to reduce healthcare expenditures. Future research should focus on the type of nonmonetary consumption of health services at household level to better understand financial protection and access to health care in Mexico. PMID- 29790596 TI - Rivaroxaban for stroke prevention in people with atrial fibrillation and diabetes mellitus. PMID- 29790597 TI - Stability of structurally entangled protein dimers. AB - We studied stretching, folding and thermodynamic properties of structurally entangled protein dimers. The tests for entanglement involve four-terminal pulling. We study the dynamics of such pulling and contrast it with the standard two-terminal one. The two-chain entanglement is qualitatively characterized by its entangled core, which is defined as the minimal structure that is entangled. The existence of the entangled cores is found to be affecting both the mechanical and folding properties of the proteins. We also show that the folding pathways of the entangled proteins are not universal but the bottleneck is always the formation of the entangled conformation. We demonstrate that entanglement enhances thermodynamic stability. PMID- 29790598 TI - Detection of lichen planus pigmentosus with dermoscopy and reflectance confocal microscopy. PMID- 29790599 TI - Towards a reliable, non-invasive melanin assessment for pigmented skin. PMID- 29790600 TI - Characterizing the tissue dielectric constant of skin basal cell cancer lesions. AB - BACKGROUND: Measuring tissue dielectric constant (TDC) of cancer tissues to distinguish them from normal or non-cancerous tissues has been an active area of research that has targeted several different cancer types usually using in vitro specimens. The goal of this study was to determine if and to what extent TDC values measured in vivo at 300 MHz using a simple hand-held measuring device might differentiate between skin cancer lesions and non-cancerous skin. MATERIALS AND METHODS: Triplicate TDC measurements were made in 32 patients who were subsequently diagnosed with skin basal cell carcinoma (BCC) and in 14 patients subsequently diagnosed as having non-cancerous lesions. Lesion TDC values were compared to contralateral unaffected skin and between lesion types. RESULTS: A significantly lower TDC value (mean +/- SD) of BCC lesions (TDCL ) vs TDC values of contralateral non-affected skin (TDCC ) was found (22.4 +/- 16.2 vs 38.1 +/- 15.2, P < .00001). A similar pattern was found for non-cancerous lesions with lesion TDC values less than non-affected skin (14.5 +/- 9.0 vs 29.1 +/- 9.0, P < .0001). However, TDC values were not statistically different between BCC lesions and non-cancerous lesions (22.4 +/- 16.2 vs 14.5 +/- 9.0, P = .096) and calculated TDCL /TDCC ratios between BCC lesions and non-cancerous lesions also were not significantly different (0.596 +/- 0.345 vs 0.501 +/- 0.261, P = .364). CONCLUSIONS: (1) Main results do not support using TDC measurements to differentiate in vivo skin cancer lesions from non-cancerous lesions. (2) TDC values strongly suggest reduced water content of both cancerous and non-cancerous lesions. (3) Lesion TDC measurements provide reference values for future studies. PMID- 29790601 TI - A method for partitioning the information contained in a protein sequence between its structure and function. AB - Proteins employ the information stored in the genetic code and translated into their sequences to carry out well-defined functions in the cellular environment. The possibility to encode for such functions is controlled by the balance between the amount of information supplied by the sequence and that left after that the protein has folded into its structure. We study the amount of information necessary to specify the protein structure, providing an estimate that keeps into account the thermodynamic properties of protein folding. We thus show that the information remaining in the protein sequence after encoding for its structure (the 'information gap') is very close to what needed to encode for its function and interactions. Then, by predicting the information gap directly from the protein sequence, we show that it may be possible to use these insights from information theory to discriminate between ordered and disordered proteins, to identify unknown functions, and to optimize artificially-designed protein sequences. PMID- 29790602 TI - Folding with a protein's native shortcut network. AB - A complex network approach to protein folding is proposed, wherein a protein's contact map is reconceptualized as a network of shortcut edges, and folding is steered by a structural characteristic of this network. Shortcut networks are generated by a known message passing algorithm operating on protein residue networks. It is found that the shortcut networks of native structures (SCN0s) are relevant graph objects with which to study protein folding at a formal level. The logarithm form of their contact order (SCN0_lnCO) correlates significantly with folding rate of two-state and nontwo-state proteins. The clustering coefficient of SCN0s (CSCN0 ) correlates significantly with folding rate, transition-state placement and stability of two-state folders. Reasonable folding pathways for several model proteins are produced when CSCN0 is used to combine protein segments incrementally to form the native structure. The folding bias captured by CSCN0 is detectable in non-native structures, as evidenced by Molecular Dynamics simulation generated configurations for the fast folding Villin-headpiece peptide. These results support the use of shortcut networks to investigate the role protein geometry plays in the folding of both small and large globular proteins, and have implications for the design of multibody interaction schemes in folding models. One facet of this geometry is the set of native shortcut triangles, whose attributes are found to be well-suited to identify dehydrated intraprotein areas in tight turns, or at the interface of different secondary structure elements. PMID- 29790603 TI - Hyperkalaemia in people with diabetes: occurrence, risk factors and outcomes in a Danish population-based cohort study. AB - AIMS: To examine the incidence, risk factors and clinical outcomes of hyperkalaemia in people with diabetes in a real-world setting. METHODS: Using Danish health registries, we identified a population-based cohort of people with first-time drug-treated diabetes, in the period 2000-2012. First, the cumulative incidence of hyperkalaemia, defined as first blood test with potassium level >5.0 mmol/l after diabetes treatment initiation, was ascertained. Second, in a case control analysis, risk factors were compared in people with vs without hyperkalaemia. Third, clinical outcomes were assessed among individuals with hyperkalaemia in a before-after analysis, and among people with and without hyperkalaemia in a matched cohort analysis. RESULTS: Of 68 601 individuals with diabetes (median age 62 years, 47% women), 16% experienced hyperkalaemia (incidence rate 40 per 1000 person-years) during a mean follow-up of 4.1 years. People who developed hyperkalaemia had a higher prevalence of chronic kidney disease [prevalence ratio 1.74 (95% CI 1.68-1.81)], heart failure [prevalence ratio 2.35 (95% CI 2.18-2.54)], use of angiotensin-converting enzyme inhibitors [prevalence ratio 1.24 (95% CI 1.20-1.28)], use of spironolactone [prevalence ratio 2.68 (95% CI 2.48-2.88)] and potassium supplements [prevalence ratio 1.59 (95% CI 1.52-1.67)]. In people with diabetes who developed hyperkalaemia, 31% were acutely hospitalized within 6 months before hyperkalaemia, increasing to 50% 6 months after hyperkalaemia [before-after risk ratio 1.67 (95% CI 1.61-1.72)]. The 6-month mortality rate after hyperkalaemia was 20%. Compared with matched individuals without hyperkalaemia, the hazard ratio for death was 6.47 (95% CI 5.81-7.21). CONCLUSIONS: One in six newly diagnosed people with diabetes experienced a hyperkalaemic event, which was associated with severe clinical outcomes and death. PMID- 29790604 TI - Synthesis of Dihydroxyalkynyl and Dihydroxyalkyl Nucleotides as Building Blocks or Precursors for Introduction of Diol or Aldehyde Groups to DNA for Bioconjugations. AB - (3,4-Dihydroxybut-1-ynyl)uracil, -cytosine and -7-deazaadenine 2' deoxyribonucleoside triphosphates (dNTPs) were prepared by direct aqueous Sonogashira cross-coupling of halogenated dNTPs with dihydroxybut-1-yne and converted to 3,4-dihydroxybutyl dNTPs through catalytic hydrogenation. Sodium periodate oxidative cleavage of dihydroxybutyl-dUTP gave the desired aliphatic aldehyde-linked dUTP, whereas the oxidative cleavage of the corresponding deazaadenine dNTP gave a cyclic aminal. All dihydroxyalkyl or -alkynyl dNTPs and the formylethyl-dUTP were good substrates for DNA polymerases and were used for synthesis of diol- or aldehyde-linked DNA. The aldehyde linked DNA was used for the labelling or bioconjugations through hydrazone formation or reductive aminations. PMID- 29790606 TI - The significance of spectrophotometric image analysis for diagnosis of the melanocytic skin tumours in association with their thickness. AB - BACKGROUND: Cutaneous melanoma is a melanocytic skin tumour, which has very poor prognosis while it is highly resistant to treatment and tends to metastasize. Thickness of melanoma is one of the most important biomarker for stage of disease, prognosis and surgery planning. In this study, we hypothesized that the analysis of spectrophotometric (SIAscope) images can provide the information about skin tumour thickness. METHODS: The intensity of blood displacement, "erythematous blush", collagen holes, intensity of collagen, dermal and epidermal melanin were estimated in SIAgraphs. Tumour thicknesses were evaluated non invasively in ultrasound images before excision. The diagnosis and Breslow index of each tumour were evaluated during routine histological examination. RESULTS: The logistic regression analysis of two thicknesses groups of melanocytic tumours (<=1 mm, n = 72 and >1 mm, n = 30), using six SIAscopic features lead to achieve the areas under the ROC curves of 0.9 and 0.96 respectively. Overall the sensitivity and specificity of SIAscopy observed in this study is 81.4% and 86.4% respectively. CONCLUSION: The features of SIAgraphs individually are not enough specific for melanoma diagnosis with different thickness. Promising results were observed for differentiation of melanocytic skin tumour, using all 6 SIAscopic features, which correspond to the distribution, location and concentration of skin chromophores. PMID- 29790605 TI - CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome. AB - Premature T-cell immunosenescence with CD57+ CD8+ T-cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T-cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory T cells showing increased PD1 and Eomesodermin expression. In addition, transition of naive to CD57+ CD8+ T cells was not associated with the characteristic telomere shortening. Nevertheless, they showed the increased interferon-gamma secretion, enhanced degranulation and reduced in vitro proliferation typical of senescent CD57+ CD8+ T cells. Thus, hyperactive PI3 kinase signaling favors premature accumulation of a CD57+ CD8+ T-cell population, which shows most functional features of typical senescent T cells, but is different in terms of differentiation and relative telomere shortening. Initial observations indicate that this specific differentiation state may offer the opportunity to revert premature T-cell immunosenescence and its potential contribution to inflammation and immunodeficiency in APDS. PMID- 29790607 TI - Rosacea-like cutaneous localization of small lymphocytic lymphoma unmasked by high-frequency-ultrasound. PMID- 29790608 TI - How accurately do force fields represent protein side chain ensembles? AB - Although the protein backbone is the most fundamental part of the structure, the fine-tuning of side-chain conformations is important for protein function, for example, in protein-protein and protein-ligand interactions, and also in enzyme catalysis. While several benchmarks testing the performance of protein force fields for side chain properties have already been published, they often considered only a few force fields and were not tested against the same experimental observables; hence, they are not directly comparable. In this work, we explore the ability of twelve force fields, which are different flavors of AMBER, CHARMM, OPLS, or GROMOS, to reproduce average rotamer angles and rotamer populations obtained from extensive NMR studies of the 3 J and residual dipolar coupling constants for two small proteins: ubiquitin and GB3. Based on a total of 196 MUs sampling time, our results reveal that all force fields identify the correct side chain angles, while the AMBER and CHARMM force fields clearly outperform the OPLS and GROMOS force fields in estimating rotamer populations. The three best force fields for representing the protein side chain dynamics are AMBER 14SB, AMBER 99SB*-ILDN, and CHARMM36. Furthermore, we observe that the side chain ensembles of buried amino acid residues are generally more accurately represented than those of the surface exposed residues. PMID- 29790609 TI - Detection of hydroquinone by Raman spectroscopy in patients with melasma before and after treatment. AB - BACKGROUND: Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans. MATERIAL AND METHODS: In this work, Raman spectroscopy was used to observe the presence of hydroquinone in the skin of 18 patients who have been under treatment for melasma. RESULTS: A significant increase in the Raman signal was observed in the six bands associated with hydroquinone after melasma treatment. CONCLUSION: The authors believe that monitoring the presence of hydroquinone may be useful for an optimal personalized treatment of melasma and to provide the specialist a support tool to control the administration of this type of bleaching agents. PMID- 29790610 TI - Highly Luminescent Dual Mode Polymeric Nanofiber-Based Flexible Mat for White Security Paper and Encrypted Nanotaggant Applications. AB - Increasing counterfeiting of important data, currency, stamp papers, branded products etc., has become a major security threat which could lead to serious damage to the global economy. Consequences of such damage are compelling for researchers to develop new high-end security features to address full-proof solutions. Herein, we report a dual mode flexible highly luminescent white security paper and nanotaggants composed of nanophosphors incorporated in polymer matrix to form a nanofiber-based mat for anti-counterfeiting applications. The dual mode nanofibers are fabricated by electrospinning technique by admixing the composite of NaYF4 :Eu3+ @NaYF4 :Yb3+ , Er3+ nanophosphors in the polyvinyl alcohol solution. This flexible polymer mat derived from nanofibers appears white in daylight, while emitting strong red (NaYF4 :Eu3+ ) and green (NaYF4 :Yb3+ , Er3+ ) colors at excitation wavelengths of 254 nm and 980 nm, respectively. These luminescent nanofibers can also be encrypted as a new class of nanotaggants to protect confidential documents. These obtained results suggest that highly luminescent dual mode polymeric nanofiber-based flexible white security paper and nanotaggants could offer next-generation high-end unique security features against counterfeiting. PMID- 29790611 TI - Anesthesia effects on the low frequency blood flow oscillations in mouse skin. AB - BACKGROUND: When laboratory animals are used one needs to anesthetize them before recording. However, the influence of anesthesia on animal blood flow oscillations has not been studied. The effects of two ways of anesthesia, zoletil-xylazine, and zoletil-nitrous oxide mixtures, on mouse skin perfusion using laser Doppler flowmetry (LDF) technique were studied. METHODS: BALB/c mice were used. LDF probe was placed on the ventral surface of the left hind paw. Spectral analysis of LDF signals was performed with continuous adaptive wavelet transform to identify and describe peripheral blood flow oscillations in mouse skin. RESULTS: Low-frequency oscillation interval boundaries (myogenic, neurogenic, and endothelial) for mice were shown to coincide with the boundaries determined for human and rats, that demonstrate their independence from the body size. Zoletil-xylazine anesthesia significantly decreased neurogenic and endothelial oscillation amplitudes by 29% and 50% respectively and increased the amplitude of cardiac oscillations by 23% compared to zoletyl-nitrous oxide anesthesia. There were no significant changes of the amplitudes of myogenic and respiratory oscillations with zoletil-nitrous oxide anesthesia compared to the zoletil-xylazine mixture. CONCLUSION: We suggest that the different influence of anesthesia modes on the amplitudes of skin blood flow oscillations is associated with sympathetic activity suppressed by zoletil xylazine anesthesia. PMID- 29790612 TI - Split-axilla comparison study of 0.5-MHz, invasive, bipolar radiofrequency treatment using insulated microneedle electrodes for primary axillary hyperhidrosis. AB - BACKGROUND: Energy-delivering devices can be used to induce thermal coagulation of the eccrine sweat glands for treating primary axillary hyperhidrosis (PAH). OBJECTIVE: The objective of this study was to compare the efficacy and safety of invasive, bipolar radiofrequency (RF) treatment for PAH. METHODS: A split-axilla study was performed to compare the clinical outcomes of 0.5 MHz, invasive, bipolar RF treatment with treatment settings of a longer conduction time and lower power (LC/LP) vs a shorter conduction time and higher power (SC/HP) for treating PAH. RESULTS: The in vivo study revealed median hyperhidrosis disease severity scale scores of 1.5 (interquartile range [IQR], 1-2) at 1 month and 1 (IQR, 1-2) at 3 months after treatment with the LC/LP setting, compared to baseline. Meanwhile, the other side of the axillae treated with the SC/HP setting showed scores of 2 (IQR, 2-2) at 1 month and 2 (IQR, 1.25-2) at 3 months. Analysis via a linear mixed model revealed a significant interaction (group, P = .011; time, P < .001; and group * time, P = .048) between treatment group and time. CONCLUSION: PAH can be effectively and safely treated with invasive, multilayered, multiple-pass, 0.5-MHz, bipolar RF treatment, particularly with LC/LP. PMID- 29790613 TI - New Vistas in Transmetalation with Discrete "AgCF3 " Species: Implications in Pd Mediated Trifluoromethylation Reactions. AB - This work describes the employment of discrete "AgCF3 " complexes as efficient transmetalating agents to PdII to surmount overlooked challenges related to the transmetalation step in Pd-catalyzed trifluoromethylation processes. We report the participation of a unique silver ate (Cs)[Ag(CF3 )2 ] complex, under stoichiometric and catalytic conditions, in the unprecedented one-pot formation of PhCF3 using PhI as starting material. Moreover, we show that the transmetalation step, which is often ignored in these transformations, can also determine the success or failure of the coupling process. PMID- 29790614 TI - Effects of oral supplementation of probiotic strains of Lactobacillus rhamnosus and Enterococcus faecium on diarrhoea events of foals in their first weeks of life. AB - Foal first diarrhoea is one of the most prominent problems in the early life of horses. Probiotics might have the potency to prevent or at least diminish neonatal diarrhoea. We hypothesised that the treatment of foals with probiotic strains of Lactobacillus rhamnosus and Enterococcus faecium starting early after birth and then daily over 2 weeks would prevent or mitigate foal heat diarrhoea. The influence of this probiotic treatment on diarrhoea incidence and growth and health performance of young foals was investigated. Thirty-four foals were randomly allocated to two groups. From day 1 to 14 of life, the foals received either placebo (PG, n = 16) or the probiotic treatment (TG, n = 18). Clinical examination was performed, and the faeces consistency score (FCS, 1-5; with diarrhoea defined by <=3) was recorded once per day in weeks 1 and 2 and once weekly in weeks 3-8 of life (WL). The body height was measured at birth and after two and eight WL. Diarrhoea occurred in the 1st WL in 19% and 61% of PG and TG foals respectively. In the 1st WL, diarrhoea lasted 0.3 +/- 0.8 and 1.6 +/- 1.4 days in PG and TG foals respectively. In the 2nd WL, diarrhoea occurred in 94% and 84% of PG and TG foals, respectively, and lasted for 3.0 +/- 1.5 and 3.7 +/- 1.6 days respectively. At least two periods of diarrhoea developed in 33% and 65% of PG and TG foals respectively. The TG foals grew slightly slower than the PG foals. The results indicated that the probiotic treatment of neonatal foals as performed in this study was not suitable to reduce diarrhoea within the first two WL, because contrary to the hypothesis, the TG foals suffered more frequently and for longer periods from diarrhoea than the PG foals. PMID- 29790615 TI - A journey into the retina: Muller glia commanding survival and death. AB - Muller glial cells (MGCs) are known to participate actively in retinal development and to contribute to homoeostasis through many intracellular mechanisms. As there are no homologous cells in other neuronal tissues, it is certain that retinal health depends on MGCs. These macroglial cells are located at the centre of the columnar subunit and have a great ability to interact with neurons, astrocytes, microglia and endothelial cells in order to modulate different events. Several investigations have focused their attention on the role of MGCs in diabetic retinopathy, a progressive pathology where several insults coexist. As expected, data suggest that MGCs display different responses according to the severity of the stimulus, and therefore trigger distinct events throughout the course of the disease. Here, we describe physiological functions of MGCs and their participation in inflammation, gliosis, synthesis and secretion of trophic and antioxidant factors in the diabetic retina. We invite the reader to consider the protective/deleterious role of MGCs in the early and late stages of the disease. In the light of the results, we open up the discussion around and ask the question: Is it possible that the modulation of a single cell type could improve or even re-establish retinal function after an injury? PMID- 29790616 TI - In vitro and in vivo metabolic profiles of fasiglifam using ultrahigh-performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry. AB - RATIONALE: Fasiglifam is an orally available and selective partial agonist of hGPR40 receptor, which was unexpectedly terminated at phase III clinical trials due to its severe hepatotoxicity. To fully understand the mechanism of action of fasiglifam, it is necessary to investigate its in vitro and in vivo metabolic profiles. METHODS: For in vitro metabolism, fasiglifam was incubated with rat or human liver microsomes in the presence of beta-nicotinamide adenine dinucleotide phosphate tetrasodium salt, glutathione (GSH) and uridine diphosphate glucuronic acid trisodium salt for 60 min. For in vivo metabolism, fasiglifam was orally administered to rats at a single dose of 20 mg/kg and the bile was collected. In vitro and in vivo samples were analyzed by the developed ultrahigh-performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and fragment ions. RESULTS: A total of eight metabolites, including an acyl-GSH adduct, were detected and identified. M1 (acylglucuronide) and M5 (carboxylic acid derivative) were the major metabolites of fasiglifam. Metabolic pathways of fasiglifam involved oxygenation, oxidative dealkylation, dehydrogenation, glucuronidation and GSH conjugation. Fasiglifam may undergo metabolic bioactivation via acylglucuronide. CONCLUSIONS: Oxidative dealkylation and glucuronidation were the predominant metabolic pathways of fasiglifam in vitro and in vivo. Metabolic bioactivation via acylglucuronide may be the perpetrator of its hepatotoxicity. Our findings would be helpful in understanding the disposition of fasiglifam as well as its hepatotoxicity. PMID- 29790618 TI - Intratendinous Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A First-In-Human Trial. AB - Despite relatively good results of current symptomatic treatments for rotator cuff disease, there has been an unmet need for fundamental treatments to halt or reverse the progress of disease. The purpose of this study was to assess the safety and efficacy of intratendinous injection of autologous adipose tissue derived mesenchymal stem cells (AD MSCs) in patients with rotator cuff disease. The first part of the study consists of three dose-escalation cohorts; the low- (1.0 * 107 cells), mid- (5.0 * 107 ), and high-dose (1.0 * 108 ) groups with three patients each for the evaluation of the safety and tolerability. The second part included nine patients receiving the high-dose for the evaluation of the exploratory efficacy. The primary outcomes were the safety and the shoulder pain and disability index (SPADI). Secondary outcomes included clinical, radiological, and arthroscopic evaluations. Twenty patients were enrolled in the study, and two patients were excluded. Intratendinous injection of AD MSCs was not associated with adverse events. It significantly decreased the SPADI scores by 80% and 77% in the mid- and high-dose groups, respectively. Shoulder pain was significantly alleviated by 71% in the high-dose group. Magnetic resonance imaging examination showed that volume of the bursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated that volume of the articular- and bursal-side defects decreased by 83% and 90% in the mid- and high dose groups, respectively. Intratendinous injection of autologous AD MSCs in patient with a partial-thickness rotator cuff tear did not cause adverse events, but improved shoulder function, and relieved pain through regeneration of rotator cuff tendon. Stem Cells 2018;36:1441-1450. PMID- 29790619 TI - Letter to the Editor of Haemophilia. PMID- 29790617 TI - Plant growth chamber design for subambient pCO2 and delta13 C studies. AB - RATIONALE: Subambient pCO2 has persisted across the major Phanerozoic ice ages, including the entire late Cenozoic (ca 30 Ma to present). Stable isotope analysis of plant-derived organic matter is used to infer changes in pCO2 and climate in the geologic past, but a growth chamber that can precisely control environmental conditions, including pCO2 and delta13 C value of CO2 (delta13 CCO2 ) at subambient pCO2 , is lacking. METHODS: We designed and built five identical chambers specifically for plant growth under stable subambient pCO2 (ca 100 to 400 ppm) and delta13 CCO2 conditions. We tested the pCO2 and delta13 CCO2 stability of the chambers both with and without plants, across two 12-hour daytime experiments and two extended 9-day experiments. We also compared the temperature and relative humidity conditions among the chambers. RESULTS: The average delta13 CCO2 value within the five chambers ranged from -18.76 to 19.100/00; the standard deviation never exceeded 0.140/00 across any experiment. This represents better delta13 CCO2 stability than that achieved by all previous chamber designs, including superambient pCO2 chambers. Every pCO2 measurement (n = 1225) was within 5% of mean chamber values. The temperature and relative humidity conditions differed by no more than 0.4 degrees C and 1.6%, respectively, across all chambers within each growth experiment. CONCLUSIONS: This growth chamber design extends the range of pCO2 conditions for which plants can be grown for delta13 C analysis of their tissues at subambient levels. This new capability allows for careful isolation of environmental effects on plant 13 C discrimination across the entire range of pCO2 experienced by terrestrial land plants. PMID- 29790620 TI - A case report on a multicentre cooperative rehabilitation programme for inhibitor positive patients with haemophilia A. PMID- 29790622 TI - Effects of alcohol exposure on the glutamatergic system: a combined longitudinal 18 F-FPEB and 1 H-MRS study in rats. AB - In a longitudinal rat model of alcohol consumption, we showed that exposure to alcohol decreased the concentration of glutamate in the prefrontal cortex, whereas a normalization occurred during abstinence. 18F-FPEB PET scans revealed that pre-exposure mGluR5 availability in the nucleus accumbens was associated with future alcohol preference. Finally, alcohol exposure induced a decrease in mGluR5 availability in the bilateral hippocampus and amygdala compared with baseline, and in the hippocampus and striatum compared with saccharin (Figure). PMID- 29790621 TI - Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy. AB - Adoptive T-cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (TSCM ) cells is expected to overcome this shortcoming as TSCM cells are close to naive T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into TSCM -like cells (iTSCM ) by coculturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9-hDLL1 cells, interleukin (IL)-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iTSCM cells. Epstein-Barr virus-specific iTSCM cells showed much stronger antitumor potentials than conventionally activated T cells in humanized Epstein Barr virus transformed-tumor model mice. Thus, adoptive T-cell therapy with iTSCM offers a promising therapeutic strategy for cancer immunotherapy. PMID- 29790623 TI - The analysis of microbial spectrum and antibiotic resistance of uropathogens isolated from patients with urinary stones. AB - PURPOSE: The characteristics and resistance patterns of urine bacteriology in patients with urinary tract stones have not been extensively studied. This study aims to investigate the microbial spectrum and antibiotic resistance of uropathogens isolated from urinary tract infections in patients with urinary stones and provide a basis for appropriate antimicrobial treatments. METHODS: The results of positive bladder midstream urine cultures and their antimicrobial susceptibility were retrospectively analysed from hospitalised patients with diagnosis of urinary calculi and urinary tract infections between January 2010 and December 2015. RESULTS: A total of 3892 samples were analysed during the study period: 2201 were female patients (56.6%) and 1691 were male patients (43.4%). The 4 most common uropathogens were Escherichia coli (48.7%), Klebsiella pneumoniae (10.4%), Enterococcus faecalis (8.7%) and Proteus mirabilis (5.2%). Both E. coli (60.8%) and Proteus mirabilis (7.5%) were higher in female patients than in male patients (32.8%; 2.3%; P < .05). ESBL-positive E. coli accounted for 59.5% of total number of E. coli, while ESBL-positive K. pneumoniae comprised 42.0% of total K. pneumoniae. The majority of uropathogens in patients with stones had high resistance to fluoroquinolones, ceftriaxone, ceftazidime, cefepime, penicillins, sulfonamides and monobactams (resistance >20%). CONCLUSIONS: The microbial spectrum in patients with urinary stones had a complex pattern. The uropathogens showed marked multidrug resistance and a large proportion of the uropathogens were able to produce beta-lactamase. PMID- 29790624 TI - Effects of rearing system on meat quality, fatty acid and amino acid profiles of Hu lambs. AB - To determine the effects of early rearing system on meat quality traits, fatty acid and amino acid profiles of meat, 48 Hu lambs were selected and randomly divided into four treatments: control lambs were ewe-reared from birth to 60 days of age (ER), while treatment lambs were segregated from their dams at 10, 20 and 30 days of age, then artificially reared with milk replacer until 60 days of age (EW10, EW20 and EW30, respectively). All lambs had no access to the milk replacer or their dams from 61 to 90 days. Creep feed was supplied ad libitum to all lambs from 15 to 90 days of age. Artificially reared lambs (EW10, EW20 and EW30) had higher (p < .05) creep feed intake, average daily gain, slaughter weight, hot carcass weight, meat ether extract content, bright meat color (lightness and yellowness) than ewe-reared lambs. The content of unsaturated fatty acids and monounsaturated fatty acids in EW10 and EW20 were greater (p < .05) than that in ER, whereas the proportions of saturated fatty acids in EW10 and EW20 were lower than that in ER (p < .05). The percentages of C18:0, C18:2, C18:3 and the ratio of polyunsaturated fatty acids and saturated fatty acids of artificially reared lambs were greater than ewe-reared lambs (p < .05). The meat proportions of leucine, alanine and proline were higher (p < .05) in artificially reared lambs than ewe-reared ones. Finally, the artificially reared system increased meat production and changed the fatty acid and amino acid profiles of meat, and it would be appropriate to rear Hu lambs artificially from 10 days with milk replacer. PMID- 29790625 TI - Managing paediatric bleeding disorder patients undergoing surgical procedures: Leveraging the electronic medical record. AB - INTRODUCTION: Individuals with bleeding disorders have a high risk of bleeding complications with surgical procedures. Careful planning and management of peri operative treatment is vital for their safety. Yet, inter-provider communication and communication between patients/families and providers is not reliable. AIM: Our haemophilia treatment centre (HTC) created a care gap report that used the electronic medical record to inform our team when patients with bleeding disorders were scheduled for procedures. METHODS: An electronic medical record based patient registry was linked to the hospital's surgical schedule and a report was run daily by HTC staff for the upcoming 14 days. We determined the number of surgeries scheduled for patients with a bleeding disorder without the knowledge of the HTC, identified by the care gap report during the 6 months prior to and 2 years after implementing the report. RESULTS: Had the report been in effect 6 months prior, the majority of surgery cases would have been detected and planned for an average of 10 days prior to the procedure. Following implementation, the report identified 62 of 225 surgeries on patients with known bleeding disorders where the HTC did not have prior communication from the patient/family or surgical team. CONCLUSION: This surgery care gap report provides the date and time of procedures on bleeding disorder patients without relying on contact from patients/families or the surgical team. Its use has resulted in an improved peri-operative process for patients with bleeding disorders undergoing surgical procedures and potentially prevented surgery cancellations. PMID- 29790626 TI - Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway. AB - Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs. Futhermore, it was showed that S1P could promote EPCs proliferation, which could be significantly inhibited by pretreatment with CAY10444 (an S1PR3 antagonist), VPC23019 (a selective S1PR(1)/S1PR(3) antagonist), or LY294002 (a PI3K inhibitor). Moveover, we discovered that S1P could significantly attenuate H2 O2 -induced apoptosis and activation of caspase 3 in vitro, while W146 (an S1PR1 antagonist), VPC23019, or LY294002 could significantly increase the activation of caspase-3 and subsequent augmented apoptosis. Our results indicated that the protective effect of S1P is mediated by activating the PI3K/Akt pathway. In addition, S1P promotion of EPCs proliferation was observed to be mainly mediated through S1PR3 and attenuation of EPCs apoptosis induced by H2 O2 was mainly mediated through S1PR1; both of these effects are mediated by activating the PI3K/Akt pathway, which provides potentially useful therapeutic targets for coronary artery disease, diabetes mellitus, and cancer treatment. PMID- 29790627 TI - Immunotolerance approach to refractory CNS bleeding in a patient with congenital factor XIII deficiency and acquired alloantibody. PMID- 29790628 TI - Metabolic syndrome and its components are associated with increased chronic kidney disease risk: Evidence from a meta-analysis on 11 109 003 participants from 66 studies. AB - BACKGROUND & AIMS: Observational studies examining the relationship between metabolic syndrome and the risk of chronic kidney disease (CKD) have reported inconclusive results. This meta-analysis was performed to resolve these controversies. METHODS: The MEDLINE, EMBASE, and PubMed databases were systematically searched from their inception until March 2016 to identify all relevant studies. Risk estimates and their corresponding 95% confidence intervals (CIs) for the associations of MetS and its components with CKD risk were extracted and pooled using a random-effects model. RESULTS: A total of 66 studies, including 18 prospective cohorts and 48 cross-sectional studies, with 699 065 CKD patients and 11 109 003 participants were included in the meta analysis. When all definitions were pooled, the presence of MetS was associated with a significant 50% increase of CKD risk (OR = 1.50, 95% CI = 1.43-1.56), with evidence of moderate heterogeneity (I2 = 72.3%, P < .001). The risk of CKD associated with MetS was higher in studies using the American Heart Association/National Heart, Lung, and Blood Institute criteria (OR = 1.68, 95% CI = 1.25-2.10) compared with those using the Adult Treatment Panel III (OR = 1.49, 95% CI = 1.42-1.56) and the International Diabetes Federation (OR = 1.32, 95% CI = 1.22-1.41) definitions. This relationship was independent of diabetes status. Moreover, all individual components of the MetS were significantly associated with CKD, and their coexistence resulted in an escalating dose-response relationship. The sensitivity and subgroup analyses established the stability of the findings. CONCLUSIONS: This meta-analysis strongly suggests that the metabolic syndrome and its components are independently associated with the increased risk of CKD. PMID- 29790630 TI - Principles of haemophilia care: The Asia-Pacific perspective. PMID- 29790631 TI - Allied health clinicians using translational research in action to develop a reliable stroke audit tool. AB - OBJECTIVE: To design and establish reliability of a local stroke audit tool by engaging allied health clinicians within a privately funded hospital. METHODS: Design: Two-stage study involving a modified Delphi process to inform stroke audit tool development and inter-tester reliability. PARTICIPANTS: Allied health clinicians. INTERVENTIONS: A modified Delphi process to select stroke guideline recommendations for inclusion in the audit tool. Reliability study: 1 allied health representative from each discipline audited 10 clinical records with sequential admissions to acute and rehabilitation services. MAIN OUTCOME MEASURES: Recommendations were admitted to the audit tool when 70% agreement was reached, with 50% set as the reserve agreement. Inter-tester reliability was determined using intra-class correlation coefficients (ICCs) across 10 clinical records. RESULTS: Twenty-two participants (92% female, 50% physiotherapists, 17% occupational therapists) completed the modified Delphi process. Across 6 voting rounds, 8 recommendations reached 70% agreement and 2 reached 50% agreement. Two recommendations (nutrition/hydration; goal setting) were added to ensure representation for all disciplines. Substantial consistency across raters was established for the audit tool applied in acute stroke (ICC .71; range .48 to .90) and rehabilitation (ICC.78; range .60 to .93) services. CONCLUSIONS: Allied health clinicians within a privately funded hospital generally agreed in an audit process to develop a reliable stroke audit tool. Allied health clinicians agreed on stroke guideline recommendations to inform a stroke audit tool. The stroke audit tool demonstrated substantial consistency supporting future use for service development. This process, which engages local clinicians, could be adopted by other facilities to design reliable audit tools to identify local service gaps to inform changes to clinical practice. PMID- 29790629 TI - Long non-coding RNA NEAT1 promoted ovarian cancer cells' metastasis through regulation of miR-382-3p/ROCK1 axial. AB - Long non-coding RNA (lncRNA) are extensively involved in various malignant tumors, including ovarian cancer (OC). In the present study, we focused on the expression and function of nuclear enriched abundant transcript 1 (NEAT1) in OC cells' metastasis. We demonstrated that NEAT1 was upregulated in OC tissue specimens and cell lines. In addition, we revealed that depression of NEAT1 inhibited OC cells' metastasis and the expression of Rho associated coiled-coil containing protein kinase 1 (ROCK1), which is a metastasis-related gene. Using online predictive software and a series of luciferase assays, we demonstrated that both NEAT1 and ROCK1 were the targets of microRNA-382-3p (miR-382-3p) and share similar microRNA responding elements (MRE). Furthermore, we illustrated that NEAT1 and miR-382-3p inhibited each other in a reciprocal manner. Finally, through antisense experiments we demonstrated that NEAT1 promoted ROCK1-mediated metastasis by functioning as a ceRNA of miR-382-3p. In summary, the findings of this study revealed that NEAT1 promoted OC cells' metastasis through regulating the miR-382-3p/ROCK1 axial. The present study might provide a new target for treating OC. PMID- 29790632 TI - Rapid and noninvasive quality control of anhydrous milk fat by PTR-MS: The effect of storage time and packaging. AB - In this study, proton transfer reaction-mass spectrometry (PTR-MS), coupled with a time-of-flight mass analyzer and a multipurpose automatic sampler, was evaluated as a rapid and nondestructive tool for the quality control of anhydrous milk fat. Anhydrous milk fats packed in cardboard and bag-in-box were compared during refrigerated shelf life at 4 degrees C for 9 months. Anhydrous milk fat samples were taken at 120, 180, and 240 days and measured by PTR-MS during storage at 50 degrees C for 11 days. Univariate and multivariate data analysis were performed in order to classify samples according to the packaging type and compare aromatic profiles. Markers related to both packaging and storage duration were identified, and all stored samples were clearly distinguishable from reference fresh samples. Significant differences in some key butter aroma compounds such as 2-pentanone, 2-heptanone, 2/3-methylbutanal, acetoin, and butanoic acid were observed between different types of packaging. During the refrigerated storage, differences related to packaging are more evident, while during the storage at 50 degrees C, the fat oxidation induced by the high temperature becomes the most relevant phenomenon independently of the packaging type. These results indicate the importance of avoiding anhydrous milk fat storage at 50 degrees C for long times during industrial production processes. All together data demonstrated the viability of PTR-MS as a rapid and high sensitivity tool in agroindustry quality control program. PMID- 29790633 TI - Diagnostic accuracy of point-of-care ultrasound for evaluation of early blood induced joint changes: Comparison with MRI. AB - INTRODUCTION: Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint bleeding. AIM: The aim of this study was to investigate whether point-of-care ultrasound (POC-US) is an accurate alternative for MRI for the detection of early joint changes. METHODS: In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X-rays were scanned using POC-US and 3 Tesla MRI. POC-US was performed by 1 medical doctor, blinded for MRI, according to the "Haemophilia Early Arthropathy Detection with Ultrasound" (HEAD-US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI). RESULTS: Knees and ankles of 24 haemophilia patients (96 joints), aged 18-34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC-US for synovial tissue was correct (overall accuracy) in 97% (CI: 91-99) with a positive predictive value of 94% (CI: 73-100) and a negative predictive value of 97% (CI: 91-100). The overall accuracy of POC-US for cartilage abnormalities was 91% (CI: 83-96) and for bone surface irregularities 97% (CI: 91-99). CONCLUSION: POC-US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC-US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes. PMID- 29790634 TI - Parenting stress and depressive symptoms in Taiwanese mothers of young children with autism spectrum disorder: Association with children's behavioural problems. AB - BACKGROUND: This study examined the severity of parenting stress and depressive symptoms in Taiwanese mothers of young children with autism spectrum disorder (ASD) compared to mothers of young children with developmental delay (DD). The associations between parenting stress, depressive symptoms, and children's behavioural problems were also tested. METHODS: The study sample included 51 young children with ASD (mean age = 31 months), 51 young children with DD (mean age = 30 months) and their mothers. RESULTS: The results confirmed that mothers of young children with ASD experienced higher levels of parenting stress and depressive symptoms than mothers of young children with DD. In addition, children's behavioural problems were robust predictors of parenting stress and depressive symptoms in mothers of young children with ASD, but not in mothers of young children with DD. CONCLUSION: The findings indicated that one of the critical goals in early intervention for young children with ASD and their families is to reduce children's behavioural problems. PMID- 29790635 TI - The effect of 12-week garlic supplementation on symptom relief in overweight or obese women with knee osteoarthritis. AB - AIMS: Chronic joint pain and stiffness, and functional disability, are the major debilitating features of osteoarthritis (OA). The aim of this study was to assess the effect of 12-week supplementation with a garlic supplement on knee osteoarthritis outcomes in overweight or obese women. METHODS: Seventy-six postmenopausal overweight or obese women (25<=BMI<=40 kg/m2 ) with medically diagnosed knee OA participated in this randomised double-blind, placebo controlled, parallel-design trial. After randomisation into 2 groups, patients received a daily dose of either 1000 mg odourless garlic tablet, or placebo, for 12 weeks. The total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as pain, stiffness and physical function subscales, were evaluated pre- and poststudy. Anthropometric parameters and body composition (using bioelectrical impedance analysis) were also assessed. RESULTS: Following 12-week supplementation in overweight or obese women with OA, stiffness (but not pain, function or WOMAC total score) was significantly lower in the garlic group compared with the placebo group (1.4 +/- 1.6 vs 2.5 +/- 1.9, P = .023). The changes in WOMAC parameters showed no statistically significant differences between the 2 groups. WOMAC total score (38.4 +/- 15.9-30.6 +/- 15.7, P = .004) and all the subscales, including pain (8.3 +/- 3.7-7 +/- 4.4, P = .026), stiffness (2.3 +/- 1.6-1.4 +/- 1.6, P = .013) and physical function (27.7 +/- 11.9-22.2 +/- 12.4, P = .001) improved significantly in the garlic group postintervention compared with pre-intervention; although pain subscale also decreased in the placebo group (9.6 +/- 3.1-6.9 +/- 3.7, P < .001). CONCLUSIONS: Although pre- to postintervention knee OA symptoms were improved in overweight or obese women receiving 12 weeks garlic supplement, there was no significant difference in WOMAC changes compared with the placebo group. Further clinical trials are required to investigate the therapeutic value of garlic ingredients, and the potential role of placebo effect, in the management of OA symptoms. PMID- 29790637 TI - Chemo-enzymatic Total Synthesis of Oxosorbicillinol, Sorrentanone, Rezishanones B and C, Sorbicatechol A, Bisvertinolone, and (+)-Epoxysorbicillinol. AB - The sorbicillinoids are a large family of fungal natural products, many of which possess highly challenging molecular architectures. Depending on their individual structures they exhibit strong biological activities ranging from radical scavenging and anti-infective properties to cytotoxicity. Despite the resulting strong biomedical potential of these natural products and the interest of synthetic chemists owing to their fascinating structures, many sorbicillinoids are currently not synthetically accessible, thus hampering in-depth biological characterization and structural diversification. By using recombinant oxidoreductase SorbC and readily accessible sorbicillin-type synthetic precursors, we have developed enantioselective, one-pot chemo-enzymatic routes to a broad range of sorbicillinoids, thereby establishing total syntheses of oxosorbicillinol, sorrentanone, rezishanones B and C, sorbicatechol A, bisvertinolone, and (+)-epoxysorbicillinol. PMID- 29790636 TI - Amino Acid Assisted Incorporation of Dye Molecules within Calcite Crystals. AB - Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic studies have investigated the cooperative effects of soluble additives. This work addresses this challenge and focuses on the combined effects of amino acids and coloured dye molecules. The experiments demonstrate that strongly coloured calcite crystals only form in the presence of Brilliant Blue R (BBR) and four of the seventeen soluble amino acids, as compared with almost colourless crystals using the dye alone. The active amino acids are identified as those which themselves effectively occlude in calcite, suggesting a mechanism where they can act as chaperones for individual molecules or even aggregates of dyes molecules. These results provide new insight into crystal additive interactions and suggest a novel strategy for generating materials with target properties. PMID- 29790638 TI - Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: A systematic review and network meta analysis. AB - This study (registered with PROSPERO, CRD42018085967) compares the efficacy (i.e. pro-cognitive effects) and acceptability of antidiabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials comparing antidiabetic agents with placebo and/or another active antidiabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4855) evaluating the effects of 6 different antidiabetic drugs (i.e. intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo. Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of antidiabetic agents in AD/MCI. Other antidiabetic agents should also be investigated in future studies. PMID- 29790639 TI - Silylarene Hydrogenation: A Strategic Approach that Enables Direct Access to Versatile Silylated Saturated Carbo- and Heterocycles. AB - We report a method to convert readily available silylated arenes into silylated saturated carbo- and heterocycles by arene hydrogenation. The scope includes alkoxy- and halosilyl substituents. Silyl groups can be derivatized into a plethora of functionalities and find application in organic synthesis, materials science, and pharmaceutical, agrochemical, and fragrance research. However, silylated saturated (hetero- ) cycles are difficult to access with current technologies. The yield of the hydrogenation depends on the amount of the silica gel additive. This silica effect also enables a significant improvement of a previously disclosed method for the hydrogenation of highly fluorinated arenes (e.g., to all-cis-C6 H6 F6 ). PMID- 29790640 TI - Proline Fingerprint in Intrinsically Disordered Proteins. AB - NMR spectroscopy is one of the main techniques used for high-resolution studies of intrinsically disordered proteins (IDPs), permitting mapping of the structural and dynamic features of all the amino acids constituting the polypeptide at atomic resolution. Only proline residues are less straightforward to characterize because they lack any amide proton, thus rendering them not directly visible in the commonly used 2D 1 H,15 N correlation experiments. However, proline residues are highly abundant in IDPs and can mediate important functions. In this work we present an easy and effective way to obtain fingerprints of proline residues in IDPs at high resolution. PMID- 29790641 TI - Potential Use of Squarates and Croconates as Singlet Fission Sensitizers. AB - The geometrical and electronic structures of 44 squarate and croconate derivatives are computationally studied by quantum chemistry methods, in the pursuit of new singlet fission sensitizers. A non-negligible singlet open-shell diradical character is observed for most of the studied molecules, which can be controlled through chemical substitution as well as by the size of the central ring. Such a diradical character is related to small singlet-triplet energy gaps, facilitating the accomplishment of the singlet fission energetic requirements. In general, the present results indicate that squarates hold superior singlet fission capabilities than croconates, although we have identified several derivatives within both families as promising singlet fission sensitizers. PMID- 29790642 TI - After parathyroidectomy: difficult short-term medical management in patients with end-stage renal disease? PMID- 29790643 TI - The association of bicycle-related genital numbness and Sexual Health Inventory for Men (SHIM) score: results from a large, multinational, cross-sectional study. AB - OBJECTIVE: To assess the association of genital numbness and erectile dysfunction in male cyclists. SUBJECTS AND METHODS: Cyclists were recruited through Facebook advertisements and outreach to sporting clubs. This is a secondary analysis of a larger epidemiological population-based study that examined sexual and urinary wellness in athletes. We queried cycling habits and erectile function using Sexual Health Inventory for Men (SHIM). RESULTS: A total of 2 774 male cyclists were included in the analysis. Amongst cyclists, there was a statistically significant increase in the trend of genital numbness presence with more years of cycling (P = 0.002), more frequent weekly cycling (P < 0.001), and longer cycling distance at each ride (P < 0.001). Less frequent use of padded shorts (odds ratio [OR] 0.14, P < 0.001) and lower handlebar (OR 0.49, P < 0.001) were associated with numbness, but body mass index (BMI) (OR 1.1, P = 0.33) and age (OR 1.2, P = 0.15) were not. In a multivariate logistic regression model, after adjusting for age, BMI, and lifetime miles (calculated by average daily cycling mileage * cycling days/week * cycling years.), there were no statistically significant differences in mean SHIM score between cyclists with and cyclists without numbness (20.3 vs 20.2, P = 0.83). However, interestingly, the subset of cyclists who reported numbness in the buttock reported statistically significantly worse SHIM scores (20.3 vs 18.4, P < 0.001). This association was not present in cyclists who reported numbness in the scrotum, penis, or perineum and remained significant after adjusting for overall biking intensity. CONCLUSION: Cyclists report genital numbness in proportion with biking intensity but numbness is not associated with worse sexual function in this cohort. PMID- 29790644 TI - CRISPR/Cas9 Assisted Multiplex Genome Editing Technique in Escherichia coli. AB - Genome editing for site-specific chromosome modification is one of the most significant techniques in biological research. While conventional techniques usually deal with one genomic locus at a time, multiple genomic targets are often required to be modified to develop microbial cell factories. Thus, it is necessary to develop techniques for simultaneous editing of multiple loci. In this work, the authors develop a CRISPR/Cas9 assisted multiplex genome editing (CMGE) technique in Escherichia coli. With this editing method, all functional parts are assembled into replicable plasmids, and stringent inducible expression systems are used to control Cas9 gene expression, which is to decouple transformation from editing process to increase editing efficiency. A modular assembly strategy is designed to enable construction of the complex multi-gRNA plasmid. With this technique, two and three loci are able to be modified with 100% and 88.3% efficiencies, while four loci can be edited with more than 30%, which are the best results reported. Although developed in model organism, the strategy of CMGE can be adapted to other prokaryotic cells. This is a well designed and illustrated technique with no special requirement, can be used by any biological lab easily. PMID- 29790645 TI - The fibrinogen prothrombin time-derived method is not useful in patients anticoagulated with low molecular weight heparins or rivaroxaban. AB - : Essentials Fibrinogen prothrombin time-derived (FIBPT-d) behavior in anticoagulated patients is under studied. FIBPT-d method overestimates fibrinogen in rivaroxaban and low molecular weight heparin samples. Unfractionated heparin and dabigatran samples showed similar bias to the control group. Rabbit brain and human recombinant thromboplastin behavior was different in rivaroxaban samples. SUMMARY: Background The fibrinogen prothrombin time-derived (FIBPT-d) method with photo-optical coagulometers is easy and economical. However, there are few reports on the behavior of this test on samples from patients anticoagulated with direct oral anticoagulants or low molecular weight heparin (LMWH). Objective To compare fibrinogen results obtained with the Clauss (FIB C) method and the FIBPT d method with two thromboplastins in anticoagulated patients. Population The study population comprised 295 consecutive anticoagulated patients: 99 treated with vitamin K antagonists (VKAs), 49 treated with unfractionated heparin (UFH), 47 treated with LMWH, 50 treated with rivaroxaban, 50 treated with dabigatran, and 100 normal controls (NCs). Methods Dabigatran samples were analyzed by the use of FIB C with HemosIL Fibrinogen C or 100 NHI thrombin units mL-1 reagents; rabbit brain and human recombinant thromboplastins with HemosIL PTFibrinogen HS plus (HS) and Recombiplastin 2G (RP) were used for FIBPT-d method. Heparin and rivaroxaban levels were assessed with HemosIL Liq antiXa with specific calibrators; dabigatran levels were determined with the HemosIL Direct Thrombin Inhibitor Assay. All assays were performed on the ACL TOP platform in two laboratories. Percentage biases for the FIBPT-d method versus the FIB C method were calculated by the use of Bland-Altman plots. Results Positive biases of the FIBPT-d method versus the FIB C method with both thromboplastins were seen in NC samples (13.7% and 18.9% for HS and RP, respectively), but biases with HS in rivaroxaban and VKA patient samples were higher than that in NC samples, at 31.9% and 34.0%, respectively. LMWH patient samples showed higher bias than NC samples: 26.5% and 29.3.0% with HS and RP, respectively. UFH and dabigatran patient samples showed similar bias as NC samples. Conclusion The FIBPT-d method should not be used in anticoagulated patients, because the FIBPT-d mathematical algorithm has been validated only in normal subjects, so overestimation could occur in these patients. PMID- 29790646 TI - Schistocytosis occurs in severely anemic B12-deficient patients and does not imply thrombotic thrombocytopenic purpura. PMID- 29790647 TI - Creating a Collaborative Care Curriculum Framework. AB - BACKGROUND: A faculty-wide approach to curriculum design is required to ensure students within all health professional courses are provided with relevant interprofessional education opportunities across their course of study. Within the Faculty of Medicine, Nursing and Health Sciences at Monash University, Australia, a Collaborative Care Curriculum Framework was developed to detail the learning outcomes for collaborative care for pre-registration students. METHODS: A six-stage process was undertaken. A working group was established, and existing literature, interprofessional frameworks and accreditation documents were analysed, and themes extracted. Consensus was obtained across the multiple professions (12 in our context) regarding the main themes and student learning outcomes. Multimedia was engaged to facilitate the communication of the framework across the faculty. DISCUSSION: Keys to the successful development of the framework included reference to profession-specific accreditation requirements, incorporating patient and student perspectives, and working with multimedia to produce clear professional documents. The outcome of the six-stage structured process was the establishment of an agreed framework for use across professions when planning an interprofessional curriculum. Subsequent benefits of developing the framework include a shared language, vision and priorities for the development of new interprofessional curriculum activities. A Collaborative Care Curriculum Framework was developed to detail the learning outcomes for pre registration students CONCLUSION: Each stage of the framework development is outlined to allow others to replicate the process in their local context. The process undertaken and the challenges encountered are described, in addition to the subsequent benefits for faculty members and students. PMID- 29790648 TI - Anxiety sensitivity mediates the relationship between exercise frequency and anxiety and depression symptomology. AB - The anxiolytic and antidepressant effects of regular physical exercise have been well documented, though the mechanisms through which exercise alleviates symptoms of emotion disorders require further investigation. Mounting research indicates that exercise reduces anxiety sensitivity, a known vulnerability factor for the development and maintenance of psychological disorders, presumably via repeated exposure to feared somatic sensations. The purpose of the present study was to examine whether anxiety sensitivity mediates the relation between exercise frequency and symptoms of anxiety and depression. A large community sample of 955 volunteers completed a demographic questionnaire, the Anxiety Sensitivity Index 3, and the Brief Symptom Inventory-18. Exercise frequency significantly predicted anxiety sensitivity, anxiety, depression, and somatization scores. Mediation analyses indicated that anxiety sensitivity mediated the association between exercise frequency and anxiety, depression, and somatization symptoms. The findings provide further support for the association between exercise and negative affective states and suggest that anxiety sensitivity may be one mechanism through which exercise reduces emotional disorder symptomology. The implications of these findings and recommendations for future research are discussed. PMID- 29790650 TI - A Redox-Based Superoxide Generation System Using Quinone/Quinone Reductase. AB - Superoxide (O2.- ) generation in biological systems is achieved through some of the most complex enzymatic systems. Of these, only xanthine/xanthine oxidase has been used for in vitro biochemical studies. However, it suffers from limitations such as a lack of suitable heterologous expression system for xanthine oxidase and the irreversible consumption and low solubility of xanthine under physiological conditions. Herein, we report a redox-based, enzyme-catalyzed system, in which autoxidation of hydroquinone to quinone via semiquinone results in superoxide generation. Quinone is reduced back to hydroquinone by using the NfsB (oxygen-insensitive nitroreductase) enzyme of Escherichia coli strain K-12 and nicotinamide adenine dinucleotide phosphate hydride (NADPH; which is regenerated by using the glucose/glucose dehydrogenase system). This new system relies on quinones that can be recycled and have superior water solubility, as well as enzymes that are heterologously expressed. By using a variety of quinones and reaction conditions, along with a comparison of real-time fluorescence, menadione has been identified as the optimal substrate for superoxide generation. The new redox-based system presents a viable alternative for studying the biochemistry of superoxide under different physiological and pathological conditions. PMID- 29790652 TI - Preparation for making clinical referrals. AB - BACKGROUND: The application of prior learning within medical curricula to real patient care is challenging. Clinical assistantships support UK medical students making the transition to postgraduate practice as doctors. This paper describes a method of teaching clinical referrals: the process of clinicians contacting colleagues for advice or services. The skills required are key to medical practice, and students should be supported to develop them in order to optimally benefit from their assistantships and prepare for practice. METHODS: The referrals workshop consisted of five diverse clinical cases that students explored in groups. Each station presented a realistic scenario. Students assimilated written information and made a telephone call to a faculty member in another room with a clinical request. After each 90-minute session students received both personalised and group feedback. EVALUATION: The workshop was delivered to 108 students over 2 days, and received positive feedback from students and faculty members. Students and faculty members particularly valued the realism of making authentic calls to unseen clinicians, the fidelity of simulated referrals and constructive feedback. They considered this excellent preparation for making referrals in the workplace. Challenges included the moderately large number of faculty members required for each workshop (seven staff) and technical issues with telephone reception. The referrals workshop consisted of five diverse clinical cases that students explored in groups DISCUSSION: These practical, scalable, replicable and well-received learning activities have addressed a key educational need by providing guidance on the integration of prior learning with the performance of core clinical tasks. It has provided valuable preparation for postgraduate practice. Our detailed description should allow others to adapt and evaluate this in their own settings. PMID- 29790651 TI - Epitheliocystis in fish: An emerging aquaculture disease with a global impact. AB - Epitheliocystis is a skin and gill disease in fish caused by pathogenic intracellular bacteria. The disease has been reported in at least 90 species of marine and freshwater fish in both the southern and northern hemispheres. It affects a number of commercially important aquaculture species, including salmon, kingfish and bream. In infected fish, cysts typically develop in the gill epithelia, promoting the fusion of gill lamellae. Infections can lead to respiratory distress and death, particularly in cultured and juvenile fish with cases rarely reported in wild fish. Modern molecular techniques are challenging the conventional wisdoms regarding the epidemiology of epitheliocystis, showing now that a number of distinct bacterial pathogens from completely different phyla can cause this disease. Here, we review the state of knowledge, including updates on aetiology, host range, diagnosis and treatments. Traditionally, bacteria from the phylum Chlamydiae were the only known pathogenic agents of epitheliocystis, but aetiology is now recognized as being more complex, including a range of Proteobacteria. Notwithstanding recent advances in identifying the pathogens, the reservoirs and modes of transmission remain largely unknown. Recent genome sequencing of the growing number of epitheliocystis agents suggests that many bacteria causing this disease are unique to individual species of fish. Environmental conditions that approach or exceed animals' physiological tolerances (e.g. atypical temperature, salinity or pH levels) are thought to contribute to disease development and progression. Empirical data and evidence concerning epidemiology, aetiology and treatments are, however, in many cases limited, highlighting the need for more work to better characterize this disease across the different hosts and locales affected. PMID- 29790649 TI - Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques. AB - The intensity of NMR signals can be enhanced by several orders of magnitude by using various techniques for the hyperpolarization of different molecules. Such approaches can overcome the main sensitivity challenges facing modern NMR/magnetic resonance imaging (MRI) techniques, whilst hyperpolarized fluids can also be used in a variety of applications in material science and biomedicine. This Focus Review considers the fundamentals of the preparation of hyperpolarized liquids and gases by using dissolution dynamic nuclear polarization (d-DNP) and parahydrogen-based techniques, such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP), in both heterogeneous and homogeneous processes. The various new aspects in the formation and utilization of hyperpolarized fluids, along with the possibility of observing NMR signal enhancement, are described. PMID- 29790653 TI - The impact of living with morbid obesity on psychological need frustration: A study with bariatric patients. AB - Guided by self-determination theory, the purpose of this study was to gain an understanding of the previous experiences of living with morbid obesity of 10 postbariatric patients enrolled in a physical activity programme. Qualitative data were collected through interviews and diarized observations. A thematic analysis revealed that participants suffered from health and mobility troubles in their daily life and experienced stigmatization and discrimination in most areas of their social functioning. Participants described how these experiences resulted in the thwarting of their basic psychological needs for autonomy, competence and relatedness. In turn, psychological need frustration contributed to negative consequences such as body image concerns, low self-esteem, anxiety and depression; controlled regulation of their eating behaviour and extrinsic goals; rigid behaviours such as avoiding social situations; and compensatory and self-defeating behaviours such as giving up diet and physical activity regimens and binge eating (i.e., oppositional defiance). This study highlights how living with morbid obesity can impair optimal functioning and well-being via experiences of psychological need frustration. PMID- 29790654 TI - Copper nanoclusters as fluorescence-quenching probes for the quantitative analysis of total iodine. AB - Tannic acid-coated copper nanoclusters (CuNCs@TA) were synthesized and used quantitatively to analyze iodine in kelp. Compared with other methods for iodine detection, the proposed method showed excellent performance. The iodine-induced linear decrease in the fluorescence intensity of CuNCs@TA allowed the quantitative detection of iodine in the range 20-100 MUM, and the limit of detection for iodine was 18 nM. The probe can be used for the determination of iodine in real samples with reliable and accurate results. Modified Stern-Volmer equation and thermodynamic calculation studies were used to discuss the quenching mechanism. PMID- 29790655 TI - Maximising yield of peripheral blood flow cytometry for chronic lymphoproliferative disorders. AB - INTRODUCTION: Flow cytometry is used in the diagnosis of haematological diseases including chronic lymphoproliferative disorders. This audit aims to ascertain the real-world indications for peripheral blood (PB) flow cytometry and which of these are associated with higher diagnostic yields. METHODS: All PB flow cytometry requests for chronic lymphoproliferative disorders from 1 January 2014 to 31 December 2014 were identified using the laboratory information system. Data including patient demographics, specialty of requestor, lymphocyte count and blood film report (if available), indications for tests and subsequent diagnosis were collected. RESULTS: A total of 185 requests with median patient age of 60 years were analysed. The main requestor was the Haematology Unit (n = 109; 58.9%) although the diagnostic yield of their requests was not significantly better than other units combined (16.5% vs 13.2%, P = .49). Factors that significantly improved the diagnostic yield of testing were older age, the presence of atypical lymphocytes on the blood film and lymphocytosis (P < .01). Constitutional symptoms and cytopenias were not found to influence the diagnostic yield. CONCLUSION: PB flow cytometry is a useful tool when used in the appropriate clinical setting. Rationalisation of testing is important to reduce the futility of testing and unnecessary health costs. PMID- 29790656 TI - Clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. AB - INTRODUCTION: Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases. OBJECTIVES: To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. METHODS: The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow-up period with a median length of 48 months (interquartile range 43-54 months). RESULTS: The study enrolled 101 post tuberculosis bronchiectasis patients and 495 non-tuberculosis bronchiectasis patients. Compared with non-post-tuberculosis bronchiectasis, post-tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow-up data indicated that both scoring systems were able to predict 48(43-54) month mortality in post tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well. CONCLUSIONS: There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post-tuberculosis bronchiectasis. PMID- 29790658 TI - Faculty development for junior health professionals. AB - BACKGROUND: The need for faculty development programmes designed to help junior health professionals fulfill their multiple roles, across various institutions, is widely acknowledged. Such programmes are usually logistically difficult for hospital clinicians to access, however, and are discipline based. In 2017, we collaborated with four health care faculties to develop a blended learning, interprofessional faculty development programme that was up to date, relevant, and accessible to clinicians working in the hospital and university settings. The purpose of our study was to explore participants' perceptions of the structure, processes and outcomes of the programme, using the conceptual framework of communities of practice. METHODS: The Clinical Teacher Training (CTT) programme included eight modules delivered using a blended learning format. Participants were provided with education literature, online activities and videos, plus in class opportunities for active participation in small interprofessional learning groups and large group sessions. Quantitative data were collected from participants by questionnaire, and then analysed using descriptive statistics. Qualitative data were collected by focus group. Framework analysis was used to code the data set using 'communities of practice' as a conceptual framework. [Faculty development] programmes are usually logistically difficult for hospital clinicians to access and are discipline based FINDINGS: Participants felt able to achieve most of the CTT programme learning outcomes through active participation, formative assessment and feedback. Participants felt that their learning was enriched through the blended learning platform, and through delivery within an interprofessional context; however, participants suggested it would be beneficial if more content was delivered through face-to-face sessions, particularly regarding 'Journal Club' and 'Mentorship' modules. Although participants felt well prepared to teach students, they felt less well prepared for assessment activities. PMID- 29790657 TI - From low to high pathogenicity-Characterization of H7N7 avian influenza viruses in two epidemiologically linked outbreaks. AB - The ability of low pathogenic (LP) avian influenza viruses (AIV) of the subtypes H5 and H7 to mutate spontaneously to highly pathogenic (HP) variants is the main reason for their stringent control. On-the-spot evidence from the field of mutations in LPAIV to render the virus into nascent HP variants is scarce. Epidemiological investigations and molecular characterization of two spatiotemporally linked outbreaks caused by LP, and subsequently, HPAIV H7N7 in two-layer farms in Germany yielded such evidence. The outbreaks occurred within 45 days on farms 400 m apart. The LP progenitor virus was identified on both farms, with its putative HP inheritor cocirculating and then dominating on the second farm. As postulated before, mutations in the hemagglutinin cleavage site (HACS) proved to be the most decisive change in the genome of HPAIV, in this case, it was mutated from monobasic (LP) PEIPKGR*GLF into polybasic (HP) PEIPKRKRR*GLF. The full-length genome sequences of both viruses were nearly identical with only ten coding mutations outside the HACS scattered along six genome segments in the HPAIV. Five of these were already present as minor variants in the LPAIV quasispecies of the LPAI-only affected farm. H7-specific seroconversion of part of the chicken population together with the codetection of LPAIV HACS sequences in swab samples of the HPAI outbreak farm suggested an initial introduction of the LP progenitor and a subsequent switch to HPAIV H7N7 after the incursion. The findings provide rare field evidence for a shift in pathogenicity of a notifiable AIV infection and re-inforce the validity of current approaches of control measures to curtail low pathogenic H5 and H7 virus circulation in poultry. PMID- 29790659 TI - A CsPbBr3 /TiO2 Composite for Visible-Light-Driven Photocatalytic Benzyl Alcohol Oxidation. AB - Halide perovskites have attracted great attention in the fields of photovoltaics, LEDs, lasers, and most recently photocatalysis, owing to their unique optoelectronic properties. The all-inorganic halide perovskite CsPbBr3 /TiO2 composite material catalyzes selective benzyl alcohol oxidation to benzaldehyde under visible-light illumination. The catalyst, which is prepared by a facile wet impregnation method, shows very good selectivity towards benzaldehyde (>99 % at 50 % conversion). Action spectra and electron spin resonance (ESR) studies reveal that photoexcited electrons formed within CsPbBr3 upon visible-light illumination take part in the reaction via reduction of oxygen to form superoxide radicals. The detailed post-catalysis characterization by UV/Vis and X-ray photoelectron spectroscopy, X-ray diffraction, and high-angle annular dark-field scanning transmission electron microscopy studies further demonstrated the good stability of CsPbBr3 in terms of morphology and crystal structure under the reaction conditions. This study sheds light on promising new photocatalytic applications of halide perovskites. PMID- 29790660 TI - Drama to promote non-verbal communication skills. AB - BACKGROUND: Non-verbal communication skills (NVCS) help physicians to deliver relationship-centred care, and the effective use of NVCS is associated with improved patient satisfaction, better use of health services and high-quality clinical care. In contrast to verbal communication skills, NVCS training is under developed in communication curricula for the health care professions. One of the challenges teaching NVCS is their tacit nature. In this study, we evaluated drama exercises to raise awareness of NVCS by making familiar activities 'strange'. METHODS: Workshops based on drama exercises were designed to heighten an awareness of sight, hearing, touch and proxemics in non-verbal communication. These were conducted at eight medical education conferences, held between 2014 and 2016, and were open to all conference participants. Workshops were evaluated by recording narrative data generated during the workshops and an open-ended questionnaire following the workshop. Data were analysed qualitatively, using thematic analysis. Non-verbal communication skills help doctors to deliver relationship-centred care RESULTS: One hundred and twelve participants attended workshops, 73 (65%) of whom completed an evaluation form: 56 physicians, nine medical students and eight non-physician faculty staff. Two themes were described: an increased awareness of NVCS and the importance of NVCS in relationship building. Drama exercises enabled participants to experience NVCS, such as sight, sound, proxemics and touch, in novel ways. Participants reflected on how NCVS contribute to developing trust and building relationships in clinical practice. DISCUSSION: Drama-based exercises elucidate the tacit nature of NVCS and require further evaluation in formal educational settings. PMID- 29790661 TI - Transanal minimally invasive surgery as a treatment option for a completely occluded anastomosis after low anterior resection: A new approach to severe anastomotic stenosis. AB - New techniques have been developed to treat severe anastomotic strictures after rectal surgery. This report describes a new approach using transanal minimally invasive surgery for the treatment of complete anastomotic occlusion. A 49-year old man presented with a completely occluded anastomosis after low anterior resection with temporary ileostomy for rectal cancer. The lumen was completely obstructed with a blind wall. A transanal surgical approach was used to treat the obstruction. Water-soluble radiopaque contrast medium was injected intraoperatively to identify the proximal lumen, and an incision was made by electrocautery until the luminal diameter was sufficient. There was no sign of bleeding or perforation after surgery. The patient underwent ileostomy takedown after all the chemotherapy sessions were completed. This report shows that transanal minimally invasive surgery is safe and feasible for the treatment of complete anastomotic occlusions requiring invasive interventions. PMID- 29790662 TI - Pathogenic characterization of porcine reproductive and respiratory syndrome virus of Indian origin in experimentally infected piglets. AB - Porcine reproductive and respiratory syndrome (PRRS) is an economically important transboundary viral disease of pigs confronting the swine industry worldwide. This study was aimed to assess the pathogenic potential of PRRS virus belonging to genotype 2 that emerged in India in 2013. Nine 6-week-old piglets were inoculated intranasally with 2 * 105.75 TCID50 /ml of PRRSV (Ind-297221/2013). Three piglets were kept as uninfected controls. Blood and nasal swabs were collected daily up to 7 days post-infection (dpi) and on alternate days subsequently. Piglets were necropsied for tissue sample collection either on death or after euthanasia on 7, 14 or 21 dpi (one uninfected control and three PRRSV-infected piglets per interval). The virus caused high fever, typical blue ear, weight loss, respiratory distress, diarrhoea and leucopenia between 2 and 8 dpi. Two infected piglets died (on 3 and 17 dpi) during the course of study. The presence of virus in serum and nasal secretion was observed up to 19 and 17 dpi, respectively, with the maximum load between 4 and 7 dpi. Seroconversion started 6 dpi and the mean PRRSV antibody titre reached up to 640 by 21 dpi. Virus load was highest in tonsils at all the intervals, whereas in spleen and lymph nodes load was higher in later intervals. Major microscopic lesions in PRRSV-infected piglets included moderate to severe interstitial pneumonia, lymphoid depletion in tonsils and lymph nodes (cystic), thymic atrophy, reactive hyperplasia followed by lymphoid depletion in spleen. PRRSV antigen was consistently demonstrated by immunoperoxidase test in the lungs, spleen, tonsils and lymph nodes. Antigen distribution was more widespread on 7 and 14 dpi than on 21 dpi. The findings establish that the Indian PRRSV is highly pathogenic to piglets. PMID- 29790663 TI - A distinctively expressed long noncoding RNA, RP11-466I1.1, may serve as a prognostic biomarker in hepatocellular carcinoma. AB - It is urgent to explore effective diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). Now, both lncRNAs and lipid metabolism are involved in tumor pathogenesis. Long noncoding RNA, RP11-466I1.1, could likely be linked to lipid metabolism according to our bioinformatics analysis, yet studies about RP11-466I1.1 expression in tumors and its potential functions are still lacking. We aimed to explore the expression and correlations with clinical features of a long noncoding RNA, RP11-466I1.1, and further analyze its diagnostic and prognostic values in hepatocellular carcinoma. Expression levels of RP11-466I1.1 were detected by quantitative real-time PCR (qRT-PCR) in tissue and serum level, and expression differences were analyzed by independent 2-tailed t tests. Clinical features were obtained, and their correlations with RP11 466I1.1 were analyzed by chi-squared test. Receiver operating characteristic (ROC) curve was performed to assess the diagnostic value. Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of RP11-466I1.1. Results showed that RP11-466I1.1 was upregulated in HCC tissues (P < .01) and serum (P < .05). Significant upregulation of RP11-466I1.1 in HCC tissues with poor histological grade (P < .01) and incomplete tumor capsule (P < .01) was found compared to that with better histological grade and complete tumor capsule, respectively. The diagnostic value of RP11-466I1.1 was not supported by ROC curve analysis (AUROC=0.665, P = .079). Yet, the significant correlation of RP11 466I1.1 with poor prognosis indicated its potential prognostic value in HCC. This study suggested that RP11-466I1.1 is distinctively expressed in HCC and may serve as a promising novel prognostic biomarker. The concrete mechanisms of RP11 466I1.1 playing roles in HCC pathogenesis need further study. PMID- 29790664 TI - The dynamics of a healthy and infected red blood cell in flow through constricted channels: A DPD simulation. AB - Understanding the dynamics of red blood cell (RBC) motion under in silico conditions is central to the development of cost-effective diagnostic tools. Specifically, unraveling the relationship between the rheological properties and the nature of shape change in the RBC (healthy or infected) can be extremely useful. In case of malarial infection, RBC progressively loses its deformability and tends to occlude the microvessel. In the present study, detailed mesoscopic simulations are performed to investigate the deformation dynamics of an RBC in flow through a constricted channel. Specifically, the manifestation of viscous forces (through flow rates) on the passage and blockage characteristics of a healthy red blood cell (hRBC) vis-a-vis an infected red blood cell (iRBC) are investigated. A finite-sized dissipative particle dynamics framework is used to model plasma in conjunction with a discrete model for the RBC. Instantaneous wall boundary method was used to model no-slip wall boundary conditions with a good control on the near-wall density fluctuations and compressibility effects. To investigate the microvascular occlusion, the RBC motion through 2 types of constricted channels, viz, (1) a tapered microchannel and (2) a stenosed-type microchannel, were simulated. It was observed that the deformation of an infected cell was much less compared with a healthy cell, with an attendant increase in the passage time. Apart from the qualitative features, deformation indices were obtained. The deformation of hRBC was sudden, while the iRBC deformed slowly as it traversed through the constriction. For higher flow rates, both hRBC and iRBC were found to undergo severe deformation. Even under low flow rates, hRBC could easily traverse past the constricted channel. However, for sufficiently slow flow rates (eg, capillary flows), the microchannel was found to be completely blocked by the iRBC. PMID- 29790665 TI - Long noncoding RNA UFC1 is activated by E2F1 and exerts oncogenic properties by functioning as a ceRNA of FOXP3. AB - Cervical cancer is one of the most common gynecologic cancers around the world. Long noncoding RNAs (lncRNAs) are considered to be important regulators of some biological processes. Recently, it has been reported that linc-UFC1 is a putative oncogene in some cancers. However, the functional roles of linc-UFC1 have not been investigated in cervical cancer. Here, it was demonstrated that linc-UFC1 expression was significantly increased in cervical cancer tissues, and its overexpression was associated with the poor survival of patients with cervical cancer. Loss-of-function assays indicated that linc-UFC1 exerted as an oncogene because it promoted the growth and metastasis of cervical cancer cells in vitro and in vivo. Mechanistic investigations revealed that linc-UFC1 upregulated FOXP3 expression through competitively binding miR-34a. Finally, luciferase reporter and chromatin immunoprecipitation (ChIP) assays provided evidence that E2F1 could directly bind to the linc-UFC1 promoter region and enhance its transcription. Taken together, our findings indicate that the linc-UFC1 expression signature may serve as a novel biomarker for the diagnosis and prognosis of cervical cancer, and it is also highlighted that the E2F1-linc-UFC1/miR-34a/FOXP3 axis may be a potentially therapeutic target of cervical cancer. PMID- 29790666 TI - Rolapitant for the prevention of nausea in patients receiving highly or moderately emetogenic chemotherapy. AB - Most patients receiving highly or moderately emetogenic chemotherapy experience chemotherapy-induced nausea and vomiting without antiemetic prophylaxis. While neurokinin-1 receptor antagonists (NK-1RAs) effectively prevent emesis, their ability to prevent nausea has not been established. We evaluated the efficacy of the long-acting NK-1RA rolapitant in preventing chemotherapy-induced nausea using post hoc analyses of data from 3 phase 3 trials. Patients were randomized to receive 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Nausea was assessed by visual analog scale during the acute (<=24 hours), delayed (>24-120 hours), and overall (0-120 hours) phases. Post hoc analyses by treatment group (rolapitant vs control) were performed on pooled data within patient subgroups receiving cisplatin-based, carboplatin-based, or anthracycline/cyclophosphamide (AC)-based chemotherapy. In the cisplatin-based chemotherapy group, significantly more patients receiving rolapitant than control reported no nausea (NN) in the overall (52.3% vs 41.7% [P < .001]; absolute benefit [AB] = 10.6%), delayed (55.7% vs 44.3% [P < .001]; AB = 11.4%), and acute (70.5% vs 64.3% [P = .030]; AB = 6.2%) phases. Similar results were observed in the carboplatin-based chemotherapy group, with significantly more patients receiving rolapitant than control reporting NN in the overall (62.5% vs 51.2% [P = .023]; AB = 11.3%) and delayed (64.1% vs 53.6% [P = .034]; AB = 10.5%) phases. In the AC-based chemotherapy group, patients receiving rolapitant or control reported similar NN rates during the overall and delayed phases. Rolapitant effectively prevents nausea during the overall and delayed phases in patients receiving cisplatin- or carboplatin-based chemotherapy. PMID- 29790667 TI - Differences in cancer survival among white and black cancer patients by presence of diabetes mellitus: Estimations based on SEER-Medicare-linked data resource. AB - Diabetes prevalence and racial health disparities in the diabetic population are increasing in the US. Population-based cancer-specific survival estimates for cancer patients with diabetes have not been assessed. The Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage provided data on cancer specific deaths and diabetes prevalence among 14 separate cohorts representing 1 068 098 cancer patients ages 66 + years diagnosed between 2000 and 2011 in 17 SEER areas. Cancer-specific survival estimates were calculated by diabetes status adjusted by age, stage, comorbidities, and cancer treatment, and stratified by cancer site and sex with whites without diabetes as the reference group. Black patients had the highest diabetes prevalence particularly among women. Risks of cancer deaths were increased across most cancer sites for patients with diabetes regardless of race. Among men the largest effect of having diabetes on cancer specific deaths were observed for black men diagnosed with Non-Hodgkin lymphoma (NHL) (HR = 1.53, 95%CI = 1.33-1.76) and prostate cancer (HR = 1.37, 95%CI = 1.32 1.42). Diabetes prevalence was higher for black females compared to white females across all 14 cancer sites and higher for most sites when compared to white and black males. Among women the largest effect of having diabetes on cancer-specific deaths were observed for black women diagnosed with corpus/uterus cancer (HR = 1.66, 95%CI = 1.54-1.79), Hodgkin lymphoma (HR = 1.62, 95%CI = 1.02-2.56) and breast ER+ (HR = 1.39, 95%CI = 1.32-1.47). The co-occurrence of diabetes and cancer significantly increases the risk of cancer death. Our study suggests that these risks may vary by cancer site, and indicates the need for future research to address racial and sex disparities and enhance understanding how prevalent diabetes may affect cancer deaths. PMID- 29790668 TI - The effects of aberrant expression of LncRNA DGCR5/miR-873-5p/TUSC3 in lung cancer cell progression. AB - Lung cancer is the most common cause of cancer-related mortality worldwide, and nonsmall cell lung cancer (NSCLC) accounts for 80% of all pulmonary carcinomas. Recently, long noncoding RNAs (lncRNAs) have been paid attention for exploring treatment of various diseases. Upregulation of DiGeorge syndrome critical region gene 5 (DGCR5) predicts better lung squamous cell carcinoma prognosis; therefore, we explore the role of DGCR5 in lung cancer in our present study. Consecutive patients with LC were treated in our hospital between January 2015 and January 2016. qRT-PCR demonstrated that DGCR5 was significantly lower in neoplastic tissues than in non-neoplastic tissues. For in vitro experiments, cell growth, migration, and invasion were significantly lower in A549 cells transfected with pcDNA3.1-DGCR5 than pcDNA3.1, which were verified by 5-diphenyltetrazolium bromide (MTT) assay, scratch test, and transwell assay, respectively, with no significant induction on cell apoptosis that was demonstrated by flow cytometry (FCM) assay. Bioinformatics analysis predicted that 3' untranslated region (UTR) of tumor suppressor candidate 3 (TUSC3, 49-55 bp) and DGCR5 (801-807 bp) shared a common hsa-miR-873-5p binding site, and the direct interaction between DGCR5 and hsa-miR-873-5p or hsa-miR-873-5p and TUSC3 was verified by dual-luciferase reporter assay. qRT-PCR demonstrated that hsa-miR-873-5p was dramatically higher and TUSC3 was significantly lower in neoplastic tissues than in non-neoplastic tissues. DGCR5 decreased the protein level of TUSC3 by miR-873-5p which was demonstrated by Western blot and immunofluorescence. The role of DGCR5 in tumorigenesis in vivo was consistent with in vitro assays, Ki-67-positive cell number (exhibited by immunohistochemical staining), tumor size, and tumor weight of A549-DGCR5 group were significantly lower in comparison with A549-control group. PMID- 29790669 TI - Genetically determined height was associated with lung cancer risk in East Asian population. AB - The association between adult height and risk of lung cancer has been investigated by epidemiology studies, but the results are inconsistent. Mendelian randomization (MR) analyses with individual-level data from two genome-wide association studies, including a total of 7127 lung cancer cases and 6818 controls, were carried out to explore whether adult height is causally associated with risk of lung cancer. A weighted genetic risk score (wGRS) was created based on genotypes of 101 known height-associated genetic variants. Association between the wGRS and risk of lung cancer was analyzed by logistic regression for each study separately. The combined effect was calculated using fixed effect meta analysis. MR analyses showed that increased risk of lung cancer (OR = 1.19, 95%CI: 1.05-1.35, P = 0.006) associated with taller genetically determined height. Compared with individuals in the lowest tertile of the height-associated wGRS, those in the highest tertile had 1.10-fold (95% CI: 1.01-1.20) increased risk of developing lung cancer. Sensitivity analyses excluding BMI-associated genetic variants demonstrated consistent association. Our study suggested that genetically taller height was associated with increased risk of lung cancer in East Asian population, indicating that increasing height may have a causal role in lung cancer carcinogenesis. PMID- 29790670 TI - Reference equations for the interpretation of forced expiratory and plethysmographic measurements in infants. AB - BACKGROUND: Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. METHODS: Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. RESULTS: The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. CONCLUSIONS: Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment. PMID- 29790671 TI - Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. AB - Breast cancer (BRCA) is the second leading cause of cancer-related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LACTB dysregulation in BRCA have not been reported. In the present study, we find that LACTB is repressed in BRCA and associated with poor prognosis by BRCA tissue microarray (TMA) analysis. Moreover, we confirm that LACTB is a direct target of miR-374a, which is significantly overexpressed and associated with malignancies in BRCA. Mechanistically, applying loss-of-function and gain-of-function approaches in a series of in vitro and in vivo experiments show that miR-374a knockdown suppresses the cell proliferative and colony formation activity, as well as migration and invasion capacity, but LACTB silencing in these cells reverses this change. Furthermore, we find that miR-374a silencing markedly reduces the tumor growth in xenograft mouse models. In summary, our findings suggest the miR-374a/LACTB axis plays a critical role in the tumorigenicity and progression of BRCA. miR-374a/LACTB axis may be a potential target in the development of therapeutic strategies for BRCA patients. PMID- 29790672 TI - Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy. AB - We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis-free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence-free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis-free survival in patients with HNC treated with RT. PMID- 29790673 TI - N-terminal-probrain natriuretic peptide as a biomarker of moderate to severe bronchopulmonary dysplasia in preterm infants: A prospective observational study. AB - OBJECTIVE: N-terminal-probrain natriuretic peptide (NT-proBNP) is a marker of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. In this study, we assessed whether NT-proBNP levels could predict the risk of moderate to severe bronchopulmonary dysplasia (BPD) and/or death. METHODS: This was an observational prospective study of preterm infants with GA <=32 weeks. Infants who died within the first 48 h or who had major congenital malformations or incomplete information were excluded. NT-proBNP was determined at 48-96 h of life and at 5-10 days of life. The predictive capacity of NT-proBNP for the combined outcome of BPD and/or death was evaluated using receiver operator characteristic (ROC) curves and multivariate regression. RESULTS: Of the 125 eligible patients, 110 completed the analysis. Twenty-eight developed BPD (n = 15) and/or died (n = 13). Infants who developed BPD and/or died had higher NT proBNP levels at 48-96 h (26,848 ng/L, interquartile range [IQR] 7818-60,684 vs 3008 ng/L, IQR 1425-9876) and at 5-10 days (8849 ng/L, IQR 3796-19,526 vs 1427 ng/L, IQR 907-2889). The NT-proBNP levels at 5-10 days, but not at 48-96 h, were independently associated with BPD and/or death after adjustments for HsPDA and other confounders (OR = 3.36; 95%CI: 1.52-7.4, P = 0.006). For the prediction of this result, a cutoff of 3348 ng/L had a sensitivity and specificity of 82% and 83%, respectively (area under the curve [AUC] = 0.87; 95%CI: 0.79-0.95). CONCLUSION: The NT-proBNP levels at 5-10 days of life may identify preterm infants with an HsPDA who are at high risk of BPD or death and may be useful for individualized preventive and therapeutic strategies. PMID- 29790674 TI - Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis. AB - PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity. PMID- 29790675 TI - Loss of cyclin-dependent kinase-like 2 predicts poor prognosis in gastric cancer, and its overexpression suppresses cells growth and invasion. AB - Cyclin-dependent kinase-like 2 (CDKL2), a new member of the cyclin-dependent kinase family, may be involved in gastric cancer (GC) progression. Thus, we conducted this study to explore the clinical effect of CDKL2 in GC. Immunohistochemistry was used to measure CDKL2 levels in gastric tissues. The association of a high CDKL2 level with clinical and pathological characteristics, and the correlation between the CDKL2 level and disease-free and overall survival were analyzed. Transfection was employed to overexpress CDKL2 in GC cells and to investigate the effect of CDKL2 overexpression on cell proliferation and invasion. Loss of CDKL2 was positively correlated with several clinical and pathological characteristics, and patients with a low CDKL2 level had significantly poorer disease-free and overall survival than those with a high level (P = .005 and .001, respectively). Univariate analysis using the Cox proportional hazards model indicated that a low CDKL2 level was a prognosticator for inferior disease-free survival (P = .007). Based on immmunoblotting data, AGS and HGC-27 GC cells were chosen for CDKL2 overexpression. Cellular studies revealed that CDKL2 overexpression impaired cell proliferation and invasion. Loss of CDKL2 may serve as a biomarker for predicting GC patient outcomes and a potential therapeutic target for GC treatment. PMID- 29790676 TI - Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma. AB - This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis. The GP regimen compared with the FP regimen had significantly higher 1-year survival rate (relative risk (RR) = 1.07, 95% confidence interval (CI): 1.01-1.13), significantly better performance in the fixed-effect model (RR = 1.16, 95%CI: 1.04-1.30) and significantly higher remission rate (RR = 1.17, 95%CI: 1.05-1.29). Significant differences between regimens were found in gastrointestinal effects (RR = 0.58, 95%CI: 0.45-0.74). No significant differences between regimens were found in reduced hemoglobin rate (RR = 0.55, 95%CI: 0.36-1.21), neutropenia (RR = 1.84, 95%CI: 0.93-5.02), or reduced platelet (RR = 1.25, 95%CI: 0.85-1.75) and mucosal inflammation (RR = 0.81, 95%CI: 0.57-1.16). Sensitivity analysis indicated the results remained stable. The funnel plot indicated some publication bias. In conclusion, the GP regimen outperforms the FP regimen in treatment of advanced nasopharyngeal carcinoma with no difference in adverse effects. We may consider the GP regimen a better choice, but this conclusion should be confirmed by high-quality trials. PMID- 29790678 TI - Pediatric pulmonology year in review 2017: Part 1. AB - Pediatric Pulmonology publishes original research, case reports and review articles on topics related to a wide range of children's respiratory disorders. In this article (Part 1 of a series), we summarize the past year's publications in our major topic areas, as well as selected literature in these areas from other journals. In Part 1, we review selected articles on diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases. PMID- 29790677 TI - Predicting healthcare outcomes in prematurely born infants using cluster analysis. AB - AIMS: Prematurely born infants are at high risk of respiratory morbidity following neonatal unit discharge, though prediction of outcomes is challenging. We have tested the hypothesis that cluster analysis would identify discrete groups of prematurely born infants with differing respiratory outcomes during infancy. METHODS: A total of 168 infants (median (IQR) gestational age 33 (31-34) weeks) were recruited in the neonatal period from consecutive births in a tertiary neonatal unit. The baseline characteristics of the infants were used to classify them into hierarchical agglomerative clusters. Rates of viral lower respiratory tract infections (LRTIs) were recorded for 151 infants in the first year after birth. RESULTS: Infants could be classified according to birth weight and duration of neonatal invasive mechanical ventilation (MV) into three clusters. Cluster one (MV <=5 days) had few LRTIs. Clusters two and three (both MV >=6 days, but BW >=or <882 g respectively), had significantly higher LRTI rates. Cluster two had a higher proportion of infants experiencing respiratory syncytial virus LRTIs (P = 0.01) and cluster three a higher proportion of rhinovirus LRTIs (P < 0.001) CONCLUSIONS: Readily available clinical data allowed classification of prematurely born infants into one of three distinct groups with differing subsequent respiratory morbidity in infancy. PMID- 29790679 TI - The influence of a 3-week body mass reduction program on the metabolic parameters and free amino acid profiles in adult Polish people with obesity. AB - BACKGROUND: Previous studies have showed differences in the amino acid (AA) composition in the plasma of people with obesity when compared to lean individuals, but the perturbations of AA concentrations in obesity and the dynamics of AA changes after weight loss is not fully understood. OBJECTIVES: The objective of the study was to evaluate the effect of a short-term weight reduction program on the metabolic status and plasma AA levels in individuals with obesity. MATERIAL AND METHODS: A total of 24 adult Polish patients with a BMI between 34 and 49 kg/m2 were enrolled in a 3-week controlled body mass reduction program based on everyday physical activity and a hypocaloric diet (25 30% less than total daily energy requirements). At baseline and after the program, anthropometric measurements, biochemical parameters and free AA profiles were determined. RESULTS: After the weight loss program, significant changes in body mass and metabolic parameters (e.g., low-density lipoprotein, triglyceride, fasting glucose, and insulin levels) were observed. Positive changes in a homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) following the program were also found. The levels of 10 AAs (alpha-amino-n-butyric acid, alanine, citrulline, glutamine, glycine, hydroxyproline, isoleucine, proline, sarcosine, and threonine) had significantly increased following weight loss. Only aspartic acid was present at a significantly lower concentration after the program. CONCLUSIONS: Using a 3 week controlled body mass reduction program based on physical activity and a hypocaloric diet, we were able to demonstrate significant changes in biochemical parameters and free AA profiles. To better understand these changes, future studies should involve a long-term program with more patients. PMID- 29790680 TI - Spirometry testing among the homeless. AB - BACKGROUND: Many literature reports have indicated the fact that the percentage of active smokers among the homeless is high, often several times higher than that of the general population. The homeless are known to have worse spirometric parameters than the general population. OBJECTIVES: The question of what the principal and exclusive cause of airway obstruction among the homeless is remains unanswered. Verification of the above-mentioned hypothesis is possible by comparing the spirometric parameters in homeless people with those in the general population, based on the data related to subgroups with similar tobacco smoke exposure, which are homogenous in terms of sex, race and age. MATERIAL AND METHODS: The spirometric parameters in 58 homeless male smokers were compared with those in 55 male smokers living normal lives. Neither group differed in age, duration of smoking or the number of pack-years. All of the subjects were Caucasian. RESULTS: The mean values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/ FVC, both corrected and expressed as absolute figures, were lower amongst the smoking homeless men than amongst men living normal lives. In 27.59% of the homeless subjests not receiving treatment for lung diseases, airway obstruction was identified. CONCLUSIONS: Our results suggest that smoking is not the only cause of the worse spirometric parameters found among the homeless. PMID- 29790681 TI - Multiple primary lung cancer: A literature review. AB - Nowadays, lung cancer is a leading cause of death in both men and women worldwide. There is no clear explanation for its mortality rate. However, it is already known that genetic and environmental factors as well as oncological treatment are involved. As the incidence of lung cancer soars, the number of patients diagnosed with multiple primary lung cancers (MPLC) is also rising. While differentiating between MPLC and intrapulmonary metastasis of lung cancer is important for treatment strategy and prognosis, it is also quite complicated, particularly in the cases with similar histologies. It is also important not to delay the diagnosis. The aim of this paper was to discuss MPLC in general, and the differentiation between MPLC and intrapulmonary lung cancer metastasis in particular. Based on a review of statistical data and the current literature, we discuss the diagnostic criteria and the molecular, genetic and radiographic methods used to distinguish between MPLC and intrapulmonary metastases. PMID- 29790682 TI - Assessment of quality of life in patients with laryngeal cancer: A review of articles. AB - This article presents a review of the medical literature published between 1994 and 2014 with the use of the PubMed database concerning quality-of-life instruments for head and neck cancer patients used to assess general well-being of patients with laryngeal cancer. The PubMed database was searched for articles containing the keywords "quality of life", "laryngeal neoplasm" and "questionnaires". The resulting articles were reviewed and analyzed. After the identification of questionnaires, an additional search was performed. The articles and questionnaires were described and analyzed. In 43 articles, the authors used questionnaires specific to the head and neck regions in order to assess the quality of life in patients with laryngeal cancer. Four different questionnaires were identified. The European Organization for Research and Treatment of Cancer (EORTC) questionnaire is most commonly used to assess the quality of life in patients with laryngeal cancer. Questionnaires are generally used in order to select from a range of different treatment methods. There are a few head and neck cancer-related quality-of-life instruments which are widely used to assess the quality of life in patients with laryngeal cancer, but they are not dedicated to that region of the body. Today, there is much more attention paid to the quality of life; therefore, there is a real need to develop specific scales for different types of cancer. PMID- 29790684 TI - The effect of music on the cardiac activity of a fetus in a cardiotocographic examination. AB - BACKGROUND: Music therapy as an adjunct to treatment is rarely used in perinatology and obstetrics, despite the proven therapeutic effect. Auditory stimulation through music positively impacts the health of adults and infants, its special role being observed in the development of prematurely born neonates. It is equally interesting how music impacts fetuses. OBJECTIVES: The aim of this study is to assess the parameters of fetuses through cardiotocographic recording in women in the 3rd trimester of pregnancy while listening to Pyotr Tchaikovsky's "Sleeping Beauty" and "Swan Lake". MATERIAL AND METHODS: The study was conducted in 2015 at Dr. Jan Biziel 2nd University Hospital in Bydgoszcz, on 48 women in the 3rd trimester of pregnancy. The cardiotocographic parameters of the fetus were examined by means of a Sonicaid Team Standard Oxford apparatus (Huntleigh Healthcare, Cardiff, United Kingdom). RESULTS: Significant changes were observed in the number of uterine contractions, accelerations, episodes of higher variability, and fetal movements after listening to the music. CONCLUSIONS: Listening to classical music can serve as a successful method of prophylaxis against premature deliveries, indicated by the lower number of uterine contractions, and in stimulating fetal movement in the case of a non-reactive non stress test (NST). Music therapy, as a therapeutic method which is inexpensive and soothing, should be used more frequently in obstetrics wards, indicated by pathological pregnancies, isolation from the natural environment, and distress resulting from diagnostics and from being in an unfamiliar environment. PMID- 29790683 TI - Surgical and oncological outcomes of free dermal fat graft for breast reconstruction after breast-conserving surgery. AB - BACKGROUND: Oncoplastic breast surgery originated in order to improve the esthetic result of breast-conserving surgery (BCS). Autologous free dermal fat graft (FDFG) is an emerging oncoplastic technique to improve the cosmetic outcome of breast-conserving surgery. OBJECTIVES: The aim of this study was to analyze our experience with FDFGs in breast reconstruction after breast-conserving surgery. Oncological outcomes, surgical complications and cosmetic results were considered. MATERIAL AND METHODS: This retrospective chart review study considered all consecutive oncoplastic breast treatment by means of FDFG reconstruction during the period between September 2011 and September 2012 in our Clinic of Surgery (University of Udine, Italy). The data collected included patient and tumor characteristics and outcomes (cosmetic and oncological). RESULTS: During the study period, 37 women were treated by breast cancer surgery and immediate breast reconstruction by FDFG. At a 3-year follow-up, we found no cases of recurrence among breast cancer patients treated by FDFG; at a 18-month follow-up, we found a prevalence of 75.0% of women extremely satisfied with their oncoplastic surgery and a high prevalence of excellent or good cosmetic outcomes (70.3%) according to objective and subjective cosmetic assessment. CONCLUSIONS: Immediate breast reconstruction by FDFG after BCS in a population selected for a low risk of breast cancer recurrence seems to be an oncologically safe option, with a good cosmetic outcome and a high prevalence of women satisfied with the treatment. PMID- 29790685 TI - F2-isoprostanes and F4-neuroprostanes as markers of intracranial aneurysm development. AB - BACKGROUND: Intracranial aneurysms are common, occurring in about 1-2% of the population. Saccular aneurysm is a pouch-like pathological dilatation of an intracranial artery that develops when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. OBJECTIVES: The aim of this study was to determine whether the development of intracranial aneurysms and subarachnoid hemorrhage (SAH) affects neuronal phospholipid metabolism, and what influence different invasive treatments have on brain free radical phospholipid metabolism. MATERIAL AND METHODS: The level of polyunsaturated fatty acid (PUFA) cyclization products - F2-isoprostanes and F4-neuroprostanes - was examined using liquid chromatography - mass spectrometry (LC-MS) in the plasma of patients with brain aneurysm and resulting subarachnoid hemorrhage. RESULTS: It was revealed that an aneurysm leads to the enhancement of lipid peroxidation with a significant increase in plasma F2-isoprostanes and F4-neuroprostanes (more than 3 fold and 11-fold, respectively) in comparison to healthy subjects. The rupture of an aneurysm results in hemorrhage and an additional increase in examined prostaglandin derivatives. The embolization and clipping of aneurysms contribute to a gradual restoration of metabolic homeostasis in brain cells, which is visible in the decrease in PUFA cyclization products. CONCLUSIONS: The results indicate that aneurysm development is associated with enhanced inflammation and oxidative stress, factors which favor lipid peroxidation, particularly in neurons, whose membranes are rich in docosahexaenoic acid, a precursor of F4 neuroprostanes. PMID- 29790686 TI - The expression of selected molecular markers of immune tolerance in psoriatic patients. AB - BACKGROUND: Psoriasis is a chronic autoinflammatory disease whose underlying molecular mechanisms remain unclear. The disease is mediated by the cells and molecules of both the innate and adaptive immune systems. Some T cell surface molecules, including neuropilin-1 (NRP1), programmed death 1 (PD-1) and the human leukocyte antigen G (HLA-G), are known to play a role in the maintenance of immune tolerance. OBJECTIVES: The aim of this study was to investigate HLA-G, NRP1 and programmed cell death gene (PDCD1) mRNA expression in psoriatic patients. MATERIAL AND METHODS: The study included 72 psoriatic patients and 35 healthy individuals. Twentyone patients (29.17%) suffered from concomitant psoriatic arthritis. The mRNA expression of HLA-G, NRP1, and PDCD1 were determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The severity of skin lesions was assessed by means of the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), the Patient Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI). RESULTS: The median value of the PASI was 11.5, and of BSA was 15.8%. The expressions of NRP1 and PDCD1, but not HLA-G, were significantly lower in psoriatic patients in comparison with the control group. The expression of HLA-G, NRP1 and PDCD1 were not significantly different in the psoriatic arthritis and psoriasis vulgaris patients. CONCLUSIONS: The results of this study suggest that the molecular markers of immune tolerance, i.e., HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients. PMID- 29790687 TI - Expression profiles of selected genes in tumors and matched surgical margins in oral cavity cancer: Do we have to pay attention to the molecular analysis of the surgical margins? AB - BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are associated with an interplay between genetics and the environment; they account for 3% of all diagnosed malignant tumors in men and 2% of those in women. OBJECTIVES: The aim of the study was to analyze the significance of TIMP3, SFRP1, SFRP2, CDH1, RASSF1, RORA, and DAPK1 gene expression in head and neck squamous cell carcinoma tumors, and in matching surgical margin samples. We also analyzed the association between clinical parameters and the expression of the selected genes. MATERIAL AND METHODS: Following surgical resection, 56 primary HNSCC tumors and matching surgical margin samples were collected from patients at the Clinic of Oncological and Reconstructive Surgery of Maria Sklodowska-Curie Memorial Cancer Center and the Institute of Oncology in Gliwice, Poland. The gene expression levels were analyzed by quantitative reverse transcription (qRT)-PCR. RESULTS: SFRP1 gene expression was statistically significantly lower in the tumor samples than in the surgical margins (0.30 +/-0.36 vs 0.62 +/-0.36; p < 0.01). No correlation was found between gene expression and clinical parameters, except DAPK1, where low expression correlated with alcohol abuse (0.85 +/-1.19 vs 1.97 +/-3.22; p = 0.074). Moreover, patients with G3 grade tumors, i.e., poorly differentiated tumors, had significantly higher values of DAPK1 gene expression than the G1 (well-differentiated tumors) and G2 (moderately differentiated) groups. CONCLUSIONS: There are many different reasons and concepts for altered gene expression in tumors and surgical margin tissue. Tumor heterogeneity and its microenvironment are undoubtedly linked to the biology of HNSCC. In order to understand specific tumor behavior and the microenvironment, further studies are needed. To find markers connected with cancer development and to provide insight into the earliest stages of cancer development, attention should also be focused on molecular analysis of the surgical margins. PMID- 29790688 TI - Loganic acid and anthocyanins from cornelian cherry (Cornus mas L.) fruits modulate diet-induced atherosclerosis and redox status in rabbits. AB - BACKGROUND: Cornelian cherry (Cornus mas L.) is a plant growing in southeast Europe, in the past used in folk medicine. There are many previous publications showing the preventive effects of (poly)phenolic compounds, especially anthocyanins, on cardiovascular diseases, but there is a lack of studies comparing the effects of (poly)phenolics and other constituents of fruits. OBJECTIVES: We have attempted to determine if iridoids and anthocyanins from cornelian cherry fruits may affect the formation of atherosclerotic plaques in the aorta as well as lipid peroxidation and oxidative stress in the livers of cholesterol-fed rabbits. MATERIAL AND METHODS: Fractions of iridoids and anthocyanins were analyzed using the high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods. Loganic acid (20 mg/kg b.w.) and a mixture of anthocyanins (10 mg/kg b.w.) were administered orally for 60 days to rabbits fed with 1% cholesterol. Histopathological samples of the aortas and the livers were stained with hematoxylin and eosin. Lipid peroxidation (malondialdehyde - MDA) and redox status (glutathione - GSH, glutathione peroxidase - Gpx and superoxide dismutase - SOD) were analyzed using spectrophotometrical methods. RESULTS: Both loganic acid (an iridoid) and a mixture of anthocyanins diminished the formation of atherosclerotic plaques in the aorta. Both substances also diminished lipid peroxidation, measured as a decrease of MDA, and attenuated oxidative stress, measured as an increase of GSH in the livers depleted by cholesterol feeding. Unexpectedly, cholesterol feeding decreased the Gpx activity in the liver, which was reversed by both investigated substances. CONCLUSIONS: We have shown that both iridoids and anthocyanins help prevent fed-induced atherosclerosis, and the consumption of fruits rich in these substances may elicit beneficial effects on the cardiovascular system. PMID- 29790689 TI - Detection of Brucella abortus by immunofluorescence assay using anti outer membrane protein of 19 kDa antibody. AB - BACKGROUND: Brucellosis in humans is one of the most prevalent zoonotic diseases around the world with more than 500,000 new cases per year. It is a weakening disease that requires long-term antibiotic treatment, often resulting in permanent and disabling consequences. Outer membrane proteins (OMPs) of Brucella, which are non-lipopolysaccharide (LPS) antigens, have been used for the diagnostic kits of brucellosis and vaccine design. OBJECTIVES: The aim of this study was to identify Brucella abortus with an immunofluorescence (IF) test using an antibody against recombinant outer membrane protein (OMP) of 19 kDa of this bacterium. MATERIAL AND METHODS: The OMP19 gene of Brucella spp. was synthesized, cloned and expressed in Escherichia coli cells. The OMP19 protein was purified by metal chelate affinity chromatography and subsequently used for the immunization of rabbits to produce a polyclonal antibody. Then, this antibody was conjugated to fluorescein isothiocyanate (FITC) and used for the detection of Brucella by an IF test. Also, the sensitivity and specificity of this antibody for the diagnosis of clinical isolates was calculated. RESULTS: Outer membrane protein 19 was expressed well and reacted with a commercial antiserum against His-tag in an immunoblot assay. Polyclonal antibodies obtained from the serum of rabbits immunized with the purified protein showed strong reactivity in the enzyme-linked immunosorbent assay (ELISA). Moreover, the polyclonal antibody conjugated to FITC was able to properly identify Brucella abortus. Sensitivity and specificity of this IF test in comparison with a polymerase chain reaction (PCR) assay was 84.2% and 50%, respectively. CONCLUSIONS: This high-titer antibody could potentially be valuable for the specific diagnostic test of brucellosis. PMID- 29790690 TI - Validation of the Portuguese version of Addenbrooke's Cognitive Examination III in mild cognitive impairment and dementia. AB - BACKGROUND: Cognitive assessment is central to the diagnosis of cognitive impairment and dementia, and it should be performed in all patients in the early stages of the disease. Recently, the 3rd version of Addenbrooke's Cognitive Examination (ACE-III) has been developed in order to improve the previous versions. OBJECTIVES: The aim of this study was to determine the psychometric properties of the Portuguese version of ACE-III, namely: reliability and discriminative validity (sensitivity and specificity) in the identification of mild cognitive impairment (MCI) and dementia, in comparison to other neuropsychological screening tests, as well as to establish its concurrent and divergent validity. MATERIAL AND METHODS: The study encompassed a sample of 90 participants distributed into 3 groups: Control (n = 30), MCI (n = 30) and Dementia (n = 30). In addition to ACE-III, Clinical Dementia Rating (CDR) and Montreal Cognitive Assessment (MoCA) were also used. RESULTS: The reliability of ACE-III was very good (alpha = 0.914). ACE-III significantly differentiated the 3 groups. The receiver operating characteristic (ROC) curves significantly favored ACE-III in comparison to another screening test - MoCA. ACE-III presented higher levels of sensitivity and specificity. Its total score correlated positively with the results on MoCA (rho = 0.912; p < 0.001) and negatively with a depression scale (rho = -0.505; p < 0.001). CONCLUSIONS: The Portuguese version of ACE-III has very good reliability and high diagnostic capacity in the context of MCI and dementia. ACE-III also holds concurrent and divergent validity. PMID- 29790691 TI - The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters. AB - BACKGROUND: Ovarian torsion is one of the most common gynecological emergencies, which especially affects women of reproductive age. OBJECTIVES: We aimed to evaluate the effect of Ginkgo biloba (GB) supplementation in ovarian ischemia/ reperfusion injury in an experimental torsion/de-torsion rat model. MATERIAL AND METHODS: This study was carried out in the Ege University Faculty of Medicine in Izmir, Turkey. Thirty mature female Sprague-Dawley albino rats were randomly divided into 5 groups: in Group 1 (control), the abdominal wall was only opened and closed; in the torsion group (Group 2), ischemia was induced for 3 h, using atraumatic vascular clips to create a torsion model; in the torsion/GB group (Group 3), the rats were given 80 mg/kg (oral gavage) of GB 30 min before torsion was induced and the torsion model was formed; in the torsion/de-torsion group (Group 4), the rats underwent 3 h of ischemia and then the vascular clips were removed and reperfusion took place for 3 h; in the torsion/de-torsion/GB group (Group 5), the rats underwent 3 h of ischemia followed by GB (oral gavage) 30 min prior to a 3-h reperfusion period. Ovarian tissue damage was evaluated by a histopathological scoring system. Ovarian tissue malondialdehyde (MDA) and plasma pentraxin-3 were measured. RESULTS: In comparison with the sham group, both the torsion and torsion/de-torsion groups had significantly higher scores for follicular degeneration, vascular congestion, edema, hemorrhage, and leukocyte infiltration. Ginkgo biloba significantly decreased these scores in both groups. Ovarian malondialdehyde and plasma pentraxin 3 were significantly higher both in the torsion and torsion/de-torsion groups compared with the sham group. Ginkgo biloba decreased these levels significantly both in the torsion/GB and torsion/de torsion/GB groups. CONCLUSIONS: Supplementing GB during a surgical procedure decreases ischemia/reperfusion injury to an ovary in an experimental rat model based on histopathological parameters, tissue malondialdehyde, and plasma pentraxin-3 levels. PMID- 29790692 TI - Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: Are we closer to understand the mechanism of action of propranolol on hemangiomas? AB - BACKGROUND: Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction. OBJECTIVES: The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications. MATERIAL AND METHODS: The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations. RESULTS: All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US. CONCLUSIONS: Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy. PMID- 29790694 TI - Advances in antibody therapeutics targeting small-cell lung cancer. AB - The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials. It was demonstrated that chemotherapy in combination with bevacizumab can improve the progression-free survival (PFS) in phase III trials. The insulin-like growth factor-1 receptor (IGF-1R) is associated with a poor prognosis in SCLC, while the anti-IGF-1R monoclonal antibody figitumumab has a potential therapeutic value. Tarextumab, an antibody that blocks both Notch2 and Notch3 signaling, in combination with etoposide and platinum (EP) in patients with untreated extensive stage SCLC, proved to be well-tolerated and showed dosedependent anti-tumor activity. The therapeutic effect of sacituzumab govitecan, BW-2 and lorvotuzumab mertansine in SCLC warranted further evaluation. Bec2/BCG as an adjuvant vaccination in patients with limited-disease SCLC could not improve the survival, PFS, or quality of life. Thus, clinical studies are essential to confirm the anti tumor efficacy of trastuzumab in SCLC. PMID- 29790693 TI - Hounsfield units from unenhanced 18F-FDG-PET/CT are useful in evaluating supradiaphragmatic lymph nodes in children and adolescents with classical Hodgkin's lymphoma. AB - BACKGROUND: The precise identification of the primarily-affected nodal regions in Hodgkin's lymphoma(HL) is essential in determining the stage of the disease and the intensity of chemotherapy and radiotherapy. OBJECTIVES: The aim of this study was to use the degree of X-ray attenuation (XRA) in Hounsfield units(HU) and the lymph node-to-muscle attenuation ratio (LN/M) in computed tomography (CT) unenhancedimaging, routinely performed with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET),to distinguish HL-affected supradiaphragmatic lymph nodes. MATERIAL AND METHODS: The study included 52 patients with classical HL treated according to the EuroNet-PHL-C1 protocol. Patients received 2 chemotherapy cycles after 18F-FDG-PET/CT testing, followedby re-examination. The lymph nodes were evaluated according to the Society for Pediatric Oncology andHematology's GPOH-HD-2002 study and Lugano criteria as not-involved (NI-LN) and involved (I-LN). RESULTS: A significant difference (p < 0.001) was found in the XRA and LN/M values between NI-LN andI-LN before treatment and after the 2 chemotherapy cycles. The optimal cut-off point for XRA (44.7 HU) andLN/M (0.79) values distinguishing I-LN from NI-LN nodes was determined by receiver operating characteristic(ROC) analysis. After 2 cycles of chemotherapy, higher XRA (p = 0.002) and LN/M (p = 0.001) values in thegroup with inadequate early CTx response were found. CONCLUSIONS: The use of XRA in HU and LN/M, together with the existing standard, can improve the qualificationof supradiaphragmatic lymph nodes in HL. PMID- 29790695 TI - Elevated beta-thromboglobulin and mean platelet volume levels may show persistent platelet activation in systemic lupus erythematosus patients. AB - BACKGROUND: Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombotic events. Platelets become more active and they enlarge to release proteins from alpha granules for aggregation during the plaque formation period. Beta-thromboglobulin is one of the proteins released from alpha-granules when platelets are activated and used as a marker of platelet activation in vivo. OBJECTIVES: The aim of this study was to evaluate the plasma levels of beta thromoglobulin and mean platelet volume as markers of the presence of platelet activation in systemic lupus erythematosus patients compared with healthy controls. MATERIAL AND METHODS: Thirty-seven SLE patients with a mean disease duration of 4.96 years and without any organ involvement as well as 30 healthy volunteers were included in the study. All patients were in remission of SLE. RESULTS: The mean beta-thromboglobulin level was 97.36 +/-55.8 ng/mL in the SLE group and 72.67 +/-33.5 ng/mL in the control group (p = 0.029). The mean platelet volume level was 8.27 +/-1.68 fL in the SLE group and 9.16 +/-1.52 fL (p = 0.031) in the controls. CONCLUSIONS: Elevated beta-thromboglobulin levels in systemic lupus erythematosus patients may be associated with platelet activation in the early stages of disease, whereas lower mean platelet volume levels in the same population may be due to the effects of hydroxychloroquine and the inactivity of SLE. PMID- 29790696 TI - Lotus tetragonolobus, Ulex europaeus, Maackia amurensis, and Arachis hypogaea (peanut) lectins influence the binding of Helicobacter pylori to gastric carbohydrates. AB - BACKGROUND: The carbohydrates of gastric mucins and other sugar structures are involved in interactions with Helicobacter pylori (H. pylori) adhesins. The binding of bacteria to mucins can protect the epithelium from direct contact with the pathogen and from developing infection because of a specific barrier created by the mucus. The pathogen also interacts with other carbohydrate structures of the epithelium. Direct contact between the bacteria and the epithelial cells facilitates infection development. OBJECTIVES: The aim of this study was to assess the influence of Maackia amurensis (MAA), Lotus tetragonolobus (LTA), Ulex europaeus (UEA), and Arachis hypogaea (PNA) lectins on the binding of gastric carbohydrates with H. pylori adhesins. MATERIAL AND METHODS: Three patients' gastric juices and 12 H. pylori strains were included in the study. An ELISA test was used to assess the presence of MUC1 and MUC5AC mucins and the sugar structures recognized by all examined lectins. The binding of the bacterium to the sugar structures was analyzed by the ELISA method with and without the gastric juices pretreated with lectins. RESULTS: In the majority of the samples examined, MAA, LTA, UEA, and PNA lectins enhanced the binding of H. pylori to specific carbohydrate structures of gastric mucins. CONCLUSIONS: Substances which influence the binding of the pathogen with specific carbohydrate receptors on gastric epithelial cells can favor inflammation development. However, if H. pylori binds with mucins, the bacterium can have difficulty reaching the epithelium and progressing with infection. PMID- 29790697 TI - The inhibition of c-MYC transcription factor modulates the expression of glycolytic and glutaminolytic enzymes in FaDu hypopharyngeal carcinoma cells. AB - BACKGROUND: Cancer cells are dependent on aerobic glycolysis for energy production and increased glutamine consumption. HIF-1alpha and c-MYC transcription factors regulate the expression of glycolytic and glutaminolytic genes. Their activity may be repressed by SIRT6. Head and neck carcinomas show frequent activation of c-MYC function and SIRT6 down-regulation, which contributes to a strong dependence on glucose and glutamine availability. OBJECTIVES: The aim of this study was to compare the influence of HIF-1alpha and c-MYC inhibitors (KG-548 and 10058-F4, respectively) and potential SIRT6 inducers - resveratrol and its synthetic derivative DMU-212 with the effect of glycolysis and glutaminolysis inhibitors (2-deoxyglucose and aminooxyacetic acid, respectively) on the metabolism and expression of metabolic enzymes in FaDu hypopharyngeal carcinoma cells. MATERIAL AND METHODS: Cell viability was assessed by means of an MTT assay. Quantitative PCR was performed to evaluate the expression of SIRT6, HIF-1alpha, c-MYC, GLUT1, SLC1A5, HK2, PFKM, PKM2, LDHA, GLS, and GDH. The release of glycolysis and glutaminolysis end-products into the culture medium - lactate and ammonia, respectively - was assessed using standard colorimetric assays. RESULTS: Lactate production was significantly inhibited by 10058-F4, KG-548, and 2-deoxyglucose. Moreover, 10058-F4 strongly reduced the amount of ammonia release. The effects of 10058-F4 activity can be attributed to a reduction in the expression of PKM2 and LDHA. On the other hand, the induction of SIRT6 expression by resveratrol and DMU-212 was not associated with significant modulation of the expression of metabolic enzymes. CONCLUSIONS: Overall, the results of this study indicate that the inhibition of c-MYC may be considered to be a promising strategy of the modulation of cancer-related metabolic changes in head and neck carcinomas. PMID- 29790698 TI - Inhibition of migration and invasion by berberine via inactivation of PI3K/Akt and p38 in human retinoblastoma cell line. AB - BACKGROUND: As a clinically important natural isoquinoline alkaloid, berberine has been reported to possess various pharmacological effects. OBJECTIVES: This study was aimed to investigate the effect of berberine on cell migration and invasion in human retinoblastoma (Rb) cells. MATERIAL AND METHODS: The cytotoxicity of berberine was estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. After being stimulated with berberine under various concentrations, the cell migration and invasion were evaluated by transwell assay. Then, the expression levels of epithelial-mesenchymal transition (EMT) markers were determined by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. Furthermore, the phosphorylation levels of protein kinase B (Akt) and p38 were detected by western blot analysis. Finally, the effect of phosphatidylinositol-3-kinase (PI3K) and p38 inhibitors on cell migration and invasion was estimated by transwell assay. Untreated cells acted as control for all the experiments. RESULTS: The concentrations of berberine for further studies were controlled in a range of 0 to 100 MUM. The cell migration and invasion were both suppressed by berberine in a dose-dependent manner compared to the control (p < 0.05 or p < 0.001). Berberine remarkably down regulated expression of E-cadherin and up-regulated expression of vimentin and alpha-SMA compared to the control (p < 0.01 or p < 0.001). Furthermore, the phosphorylation levels of Akt and p38 were both down-regulated by berberine in comparison to the control. Furthermore, the addition of berberine accompanied by LY294002 or SB203580 significantly suppressed cell migration and invasion compared to the addition of berberine alone (p < 0.05). CONCLUSIONS: Berberine suppressed cell migration and invasion via inactivation of PI3K/Akt and p38. PMID- 29790699 TI - Evaluation of the secretion and release of vascular endothelial growth factor from two-dimensional culture and three-dimensional cell spheroids formed with stem cells and osteoprecursor cells. AB - BACKGROUND: Co-culture has been applied in cell therapy, including stem cells, and has been reported to give enhanced functionality. OBJECTIVES: In this study, stem-cell spheroids were formed in concave micromolds at different ratios of stem cells to osteoprecursor cells, and the amount of secretion of vascular endothelial growth factor (VEGF) was evaluated. MATERIAL AND METHODS: Gingiva derived stem cells and osteoprecursor cells in the amount of 6 * 105 were seeded on a 24-well culture plate or concave micromolds. The ratios of stem cells to osteoprecursor cells included: 0:4 (group 1), 1:3 (group 2), 2:2 (group 3), 3:1 (group 4), and 4:0 (group 5). RESULTS: The morphology of cells in a 2-dimensional culture (groups 1-5) showed a fibroblast-like appearance. The secretion of VEGF increased with the increase in stem cells, and a statistically significant increase was noted in groups 3, 4 and 5 when compared with the media-only group (p < 0.05). Osteoprecursor cells formed spheroids in concave microwells, and no noticeable change in the morphology was noted with the increase in stem cells. Spheroids containing stem cells were positive for the stem-cell markers SSEA-4. The secretion of VEGF from cell spheroids increased with the increase in stem cells. CONCLUSIONS: This study showed that cell spheroids formed with stem cells and osteoprecursor cells with different ratios, using microwells, had paracrine effects on the stem cells. The secretion of VEGF increased with the increase in stem cells. This stem-cell spheroid may be applied for tissue-engineering purposes. PMID- 29790700 TI - Early hypophosphatemia in very low birth weight preterm infants. AB - Background: Refeeding Syndrome (RFS) is a well-known group of symptoms which occur after the introductionof enteral or parenteral nutrition in undernourished patients. Intrauterine growth restriction (IUGR)is the equivalent of postnatal RFS following the beginning of feeding. The aggressive parenteral nutritionof neonates with very low birth weight (VLBW) resulting from the termination of intrauterine transplacentalnutrition is a source of biochemical disorders. Objectives: The aim of this study was to analyze metabolic disorders in preterm infants during the 1st weekof life and to determine the hypophosphatemia risk factors in low birth weight neonates receiving parenteralnutrition. The retrospective analysis covered 49 neonates, aged between 24 0/7 and 32 6/7 weeks of gestation. Material and methods: The examined patients were divided into 2 groups according to the level of phosphatesduring the 1st week of life: HP (n = 18) with aggravated hypophosphatemia (<=3.1 mg/dL) and NP(n = 31) with normal phosphatemia (>3.1 mg/dL). Results: Hypophosphatemia was observed in the first days of life in 61% of children, in 45% of whoma subsequent test revealed a further fall in the phosphate level. In the rest of the preterm neonates (39%),hypophosphatemia was revealed between the 4th and 7th day of life. The risk of early hypophosphatemiawas higher in neonates with IUGR (p = 0.0001; RR 5.2, 95% CI 2.2-12.4) and extremely low birth weight(ELBW) preterm infants (p < 0.05). Conclusions: Early hypophosphatemia should be closely monitored early in life, especially in newborns withELBW and IUGR. Further research is needed to develop an optimal nutritional regimen from the first days of life. PMID- 29790702 TI - PRACTICE Stepping into a culture of safety Onboarding programs help retain nurses, strengthen patient care. PMID- 29790701 TI - The clinical importance of changes in Treg and Th17 lymphocyte subsets in splenectomized patients after spleen injury. AB - BACKGROUND: Splenectomized patients are more prone to bacterial infections due to their immunocompromised status. Little is known about the role of T helper 17 (Th17) and T regulatory cells (Treg) in the immune system of patients after the removal of the spleen. OBJECTIVES: The aim of the present study was to analyze possible changes in CD4+ lymphocyte T subsets, especially Treg and Th17, in patients who had undergone splenectomy. MATERIAL AND METHODS: The study included a group of 67 male patients (41.74 +/-16.22 years). All patients had undergone splenectomy because of spleen injury. Mean time elapsed from splenectomy to analysis was 9.1 +/-4.6 years. Control samples were obtained from 20 male healthy volunteers. The percentages and absolute counts of Th17 and Treg were measured using the flow cytometry method. RESULTS: The analysis of the antibody titer against 23 serotypes of Streptococcus pneumoniae (S. pneumoniae) in the splenectomized patients revealed its elevated values compared to controls (p = 0.0016). Higher percentages and absolute counts of Treg cells were found in the splenectomized group vs controls (p < 0.000007). Lower percentages and absolute counts of the Th17 subset were found in the study group vs controls (p < 0.000002 and p < 0.00006, respectively). The Treg cell percentage was positively correlated with the antibody titer against S. pneumoniae (p < 0.02). Th17 cells were reversely correlated with the antibody titer (p < 0.004 and p < 0.001 for absolute counts and percentage values, respectively). The Th17 subset values were significantly lower in the splenectomized patients who reported a higher frequency of upper respiratory tract infections (URTI) (p < 0.0001). No correlations were found between the time elapsed since splenectomy and the Treg or Th17 cell values in the study group. CONCLUSIONS: Splenectomy results in an important deterioration of the Treg/Th17 cell balance with a predominance of immunoregulatory Tregs, which can contribute to insufficient immune response to infection. PMID- 29790703 TI - SAFETY Supply and demand Health care professionals share information, strategies on drug shortages. PMID- 29790704 TI - Partnering to promote safety in the nursing profession. PMID- 29790705 TI - Addressing the challenge of medication errors. PMID- 29790706 TI - NURSING PRACTICE AND WORK ENVIRONMENT Beyond folding washcloths: An innovation for diversional activity. PMID- 29790707 TI - APRN FOCUS The role of clinical nurse specialists in transforming health care. PMID- 29790708 TI - [FETAL LOSSES DURING THE MATURATION OF THE PLACENTA AND THE RELATIONSHIP WITH SOME PROCOAGULANT CONDITIONS.] AB - Among the major causes and risk factors for fetal loss are chromosomal abnormalities, genetic syndromes, placental abnormalities, thrombophilia (FVL, Fil G20210A, C677T MTHFR, PAl-1 4G /-5G), infection and inflammation (IL-3, IL-4, IL-17, IL-10), antiphospholipid syndrome, maternal diseases such as hypertension, diabetes and obesity. Pregnancy is a prothrombotic state as a result of specific physiological changes with multifactorial ethio-pathogenesis, leading to increased procoagulant factors and structural changes turned a sTasis, inflammatory component and contribution of individual genetic and acquired thrombophilic risk factors. Understanding of the molecular mechanisms of control over the process of embryogenesis, placentation and fetal development and impact of the factors of hemodtasis, inflammation and apoptosis, contributes to the application- of appropriate therapy and increase the chance of successful completion of pregnancy. PMID- 29790709 TI - [INFLUENCE OF DIANATALO OBSTETRIC GEL ON THE LENGTH OF SECOND STAGE OF LABOR.] AB - One of the risk factors for the occurrence of occult anal sphincter injuries (OASIS) and pelvic floordamage is the increased duration of the second stage of labor; leading to a relatively high incidence of perineal trauma, which in the majority of cases remains unrecognized. If we can decrease the duration of second stage of labor we could also expect a statistically significant decrease the incidence of OASIS in clinical practice. Purpose and Goals To identify changes in the length of the second slage of labor fater adminidtration of Dianatal(r) obstetric gel. Material and methods The study enrolled 33 primiparous women after vaginal delivery in General Hospital Trbovlje, Slovenia between January and June 2012. We also included 19 more patients, delivered between May and July 2011 in the Department of Obstetrics, University Hospital - Pleven, and 8 patients, delivered between February and October 2013 in Women's Health Hospital "Nadezhda" - Sofia Results We were able to observe a significant decrease in second slage of labor in relation with administration of Dianatal(r) obstetric gel. Discussion Shortening the period of expulsion of the fetus through the use of obstetric gel can significantly reduce the incidence of birth trauma and minimize complications related to delivery trauma - anal and urinary incontinence, changes in the statics of pelvic organs, sexual dysfunction and as a result poor quality of life. PMID- 29790710 TI - [EVALUATION OF INCIDENCE OF POSTPARTUM OCCULT ANAL SPHINCTER INJURIES BY ENDOANAL ULTRASONOGRAPHY.] AB - The estimated overall risk of intrapartum damage of the anal sphincter (IUAS) is 1% of all vaginal births. The so called "occult" anal sphincter injuries (defects of the anal sphincter established by endoanal ultrasonography - OASIS) occur in 33% of primiparous women after vaginal birth. The most logical explanation for OASIS is that they are either completely missed or detected, but not mentioned in the patient's documentation, or erroneously classified as a low grade tear. Objectives To es7ablish the actual values of OASIS in the study population using endoanal ultrasonography. Material and methods The study included 29 vaginal deliveries in Porodnisnica Ljubljana in the January to June 2009 period, and 34 patients from July 2009 to May 2010, who gave birth in ObsTetric Clinic of the University Hospital - Pleven. Results The identified UAS frequency in our dtudy (25.4%) confirms the results of the incidence of such damage, cited in the literature. Discussion The results vary extensively from reported frequency of anal sphincter injuries among researched population, reflecting underesTimation of the problem, diagnostic gaps and inadequate clinical management behavior and tracking patients. PMID- 29790711 TI - [MICROSATELLITE INSTABILITY AND SURVIVAL IN PATIENTS WITH ENDOMETRIAL CANCER.] AB - Microsatellite-unstable genotype associated with deficiency mismach repaired enzymes leads to the accumulation of a series of mutations in the coding and regulatory regions of the genes having a role in carcinogenesis in endometrial cancer (ECs). The aim of this study was to investigate the correlation between the expression of four main mismach repaired enzyme (MLH-1, MSH-2, MSH-6 and PMS 2) with patients survival. ECs from 70 women (median of 63 years, range of 43-79 years) were assessed immunohistochemically for microsatellite instability (MSI). In our study we found that the presence of MSI, determined by the absence of immunohistochemically expression of at least one of the test four of the enzyme mismach repaired system is associated, not statistically significant, with longer survival (p = 0.558). In conclusion we may state that the immunohistochemical analysis who indicates MSI in biopsy tissue is a one step forward for the determination of survival and progression of endometrial carcinoma. PMID- 29790712 TI - [LAPAROSCOPIC MYOMECTOMY AFTER ULIPRISTAL ACFTATF TRFATMFMT.] AB - Uterine myoma is the most common benign uterine tumor in women of reproductive age and occurs in 20-25 % of the worldwide population. Heavy menstrual bleeding, pelvic pressure and pain and reproductive disfunction are common symptoms that impair women's health and quality of live. No currently approved medical treatment is able to completely eliminate fibroids. Until recently, gonadotropin releasing hormone agonist were the only available drugs for preoperative treatment of fibroids. Since February 2012, ulipristal acetate (UPA) is also approved in Europe for preoperative fibroid treatment. One-third from them need adjuvant surgical treatment. PMID- 29790713 TI - [THE ROLE OF COLPOSCOPY AS A METHOD OF METHODOLOGY FOR EARLY AND RAPID ETIOLOGIC DIAGNOSIS IN THE STUDY OF ENDOCERVICITIS CHLAMYDIALIS.] AB - The aim of this study was: 1. To analyze and study the specifics of colposcopic picture of ecto-and endo-cervix in endocervicitis chlamydialis. 2. To demonstrate the leading role of colposcopy method as part of the methodology for early and rapid etiologic diagnosis of chlamydial cervicitis in order to conduct etriotropian treatment.Results 1. Determine the frequency of incidence of endocervicitis chlamydialis, to cause Chl.trachomatis 45,1%, (319 DIF(+) patients out of 708 surveyed), p <0.05 in the Ruse region. 2. Demonstrated statistically significant relationship between the incidence of endocetvicitis chlamydialis, examined by DIF, and the presence of colposcopic amendments Baza and Ectopia. The difference of the two samples in terms of variable baza e statistically significant. The difference of the two samples in terms of variable ectopia e statistically significant at alpha<0,05, and when alpha<0,1 statistically significant. 3. There was no statistically significant association between the incidence of endocervicitis chlamydialis, proven by DIF, and the presence of colposcopic changes - mosaic zone of transformation, presence of blood vessels. 4.It has been proven leading role of colposcopy method as a method complementary to the early and rapid diagnosis of endocervicitis chlaamydialis, in order to hold further etiotrop treatment. PMID- 29790714 TI - [ULTRASOUND OF THE PLACENTA. NORMAL FINDINGS AND PLACENTAL ABNORMALITIES: A REVIEW.] AB - The placenta has a fundamental role for fetal growth and health throughout pregnancy. Normal placental function is essential for a healthy pregnancy outcome. A complete ultrasound survey at any stage of the pregnancy should include full assessment of the fetus and placenta. Timely detection of placental abnormalities cbn give the clinician the opportunity to make important management decisions. The primary aim is healthy pregnancy outcome. Prenatal diagnosis and correct obstetric managment reduce fetal and maternal morbidity and mortality. Familiarity with the normal and abnormal imaging appearance of the placenta is therefore necessary for the obstetrician. Despite the fundamental role of the placenta for the pregnancy outcome, ultrasound examination of the placenta is often considered secondary to the fetus. Location, size, shape and architecture are easily ascertained with two-dimensional techniques. Three-dimensional techniques and Doppler techniques are more detailed methods for evaluation uteroplacental structure and function. PMID- 29790715 TI - [NEW TECHNIQUE FOR UTERINE ARTERY IDENTIFICATION.] AB - Laparoscopic myomectomy and total laparoscopic hysterectomy are challenging surgical procedures for gynecologists, which can result in great blood loss. Most of the conversions to laparotomy happened because of intraoperative bleeding. Blocking uterine perfusion during,, Class II" laparoscopic procedures is valuable and feasible for the management of our patients. We present our modification of uterine artery identification and clipping. PMID- 29790716 TI - [TRANSVAGINAL LAPAROSCOPY FOR PELVIC ENDOMETRIOSIS.] AB - Transvaginallaparoscopy (TVL) has been described by S. Gords in 1990's. Comparig to histerosaqlpingograpy (HSG) it allows visualization of tubal mucosa. Transvaginal laparoscopy is alternative of conventional laparoscopy for infertility patients. It has significant advantage regarding minimal invasiveness and absence of abdominal incisions. Literature data shows 96.1% accuracy of TVL against laparoscopy regarding operative findings. Presence of operative port ensures possibility of doing minimal interventions like adhesiolysis, ovarian drilling and endometrioma ablation. Although these advantages this procedure is not very popular in our country yet. PMID- 29790718 TI - Ultrasound/CT combined with CA125 in the diagnosis and prognosis prediction of primary ovarian tumors. PMID- 29790717 TI - [POST-PARTUM SEPTIC SACROILIITIS- CASE REPORT AND REVIEW.] AB - : The incidence of septic postparten sacroilitis is low, described in the literature cases are less than 20 in number. CLINICAL CASE: It is about a girl 17 years and 9 months,transported to OG Clinic at University Hospital "St. George" 10 days after a normal vaginal delivery, with complaints of fever and debilitating hip pain in left gluteal area. Streptococcus pyogenes was isolated as in the culture of lochial secretions, as well as in the tested blood culture. The data obtained from completed development. The patient was subjected to a total of 6 weeks of antibiotic therapy. Conclusion Timely diagnosis of the condition is challenging because of its nonspecific clinical manifestations. Septic sacroilitis should be considered in the differential diagnosis when all women in puerperium, presenting with disablina hip pain and fever. PMID- 29790719 TI - Less is more: the "As Less As Reasonably Achievable Stenting" (ALARAS) strategy in the femoropopliteal area. AB - Although evidence supports that the performance of drug coated balloons seems to be lesion complexity independent, it is quite clear that in long lesions, severe calcified lesions and chronic total occlusions, the bail out stent ratio is very high and that the "leaving nothing behind" strategy remains a dream in a lot of our daily cases. On the other side of the spectrum, "full metal jackets" of nitinol stents are creating even more problems. Stent fractures, intimal hyperplasia and reintervention difficulties complicate the recurrent vascular disease treatment. The go-between with the "As Less As Reasonably Achievable Stenting" strategy (ALARAS), earlier named with a bad name "spot" stenting, seems the most attractive one. Scaffolding where needed and allowing freedom of vessel motion will lead to reduction of target lesion revascularization (TLR) rates. New technologies like the Tack Endovascular System and the Vascuflex MultiLOC MSD are responding very well tot this idea. Animal tests and pivotal trials (like TOBA and LOCOMOTIVE trials) already showed with both devices good results in terms of patencies and freedom from target lesion revascularizations, and with less metallic implants. Primary patency at 12 months was 76.4% and 85.7% in the TOBA and LOCOMOTIVE trial respectively. Target lesion revascularization at 12 months was 10.5% and 9.3%, respectively. In an era of "leaving nothing behind," post angioplasty dissections are more frequent than ever. With a direct link between lesion complexity, dissections and increase of TLR rates, scaffolding solutions remains essential. The ALARAS strategy tries to leave as little metal behind as possible, minimizing the risk of stent fractures, allowing freedom of vessel motion and reducing TLR rates. However, the lack of clear strategies and guidelines in where to scaffold which kind of dissections is the biggest issue at the moment. More objective classifications based on newer types of imaging like intraoperative ultrasound, intravascular ultrasound, optical coherence tomography, and/or fractional flow reserve pressure wire gradient measurements will potentially offer more solutions in this interesting field. PMID- 29790721 TI - Techniques and outcomes of secondary endovascular repair for postdissection TAA/TAAA. AB - Postdissection aortic aneurysms (PDAA) affect 20-40% of patients with aortic dissection. Open repair remains the first line therapy of PDAA, but is still associated with high mortality and morbidity rates. Endovascular repair is increasingly being used as a less invasive treatment option. Thoracic endovascular aneurysm repair (TEVAR) covering only the proximal entry tear has proven to be insufficient in most patients with chronic PDAA and has a limited role only for PDAA with distal sealing zone in the thoracic aorta. In PDAA extending to the thoracoabdominal aorta, a more complex repair is needed to achieve aneurysm exclusion. Fenestrated and branched stent-grafts have been used lately in some expert centres to treat PDAA of the thoracoabdominal aorta with good preliminary results despite the technical difficulties in these patients (narrow true lumen, stiff chronic dissection flap, target vessels that originate from the false lumen [FL]). A subset of patients with aneurysmal degeneration mainly in the descending thoracic aorta, can be treated with TEVAR landing proximal to the celiac artery along with adjuvant techniques such as coils, plugs, glue or "Candy-Plug" and "Knickerbocker" concepts to occlude the FL, preventing retrograde flow and reducing the pressure in the aneurysm. Other options that have been used in limited numbers of patients with PDAA include the PETTICOAT (provisional extension to induce complete attachment) and STABILISE (Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair) techniques. This article aims to review the outcomes of different endovascular techniques and strategies available for the repair of PDAA. PMID- 29790720 TI - Recanalization of CTOs with SoundBiteTM Active Wire. AB - BACKGROUND: The aim of this study was to examine the safety and efficacy of the SoundBiteTM Crossing System for the recanalization of infrainguinal chronic total occlusion (CTO) lesions. CTOs are frequent among patients with severe claudication or critical limb ischemia. Failure to recanalize CTOs remains common and is associated with poor prognosis. The SoundBiteTM Crossing System (SoundBite Medical Solutions Inc., Montreal, QC, Canada) is a newly developed device that uses a 0.018-inch wire (SoundBiteTM Active Wire) to deliver acoustic shock waves to the distal tip of a steerable guidewire to facilitate directed penetration of the proximal cap and crossing of the occlusion. METHODS: Symptomatic patients with de novo infrainguinal CTOs from 3 centers were enrolled in a prospective, single-arm feasibility study. The primary endpoint was 30-day device success defined as composite of technical success, defined as penetration and progression within the CTO with the SoundBiteTM Active Wire followed by complete recanalization, and freedom from device-related major adverse events including death, urgent amputation, clinically-driven target vessel revascularization, perforation, type >=C dissection, or distal embolization requiring intervention. RESULTS: Thirty-seven patients including 41 CTO lesions were enrolled in this study. CTO length ranged from 10 mm to 270 mm (mean 97.9+/-77.4 mm), and moderate to-severe calcification was present in 24 (58.5%) of the treated lesions. CTOs were successfully crossed in 34 (91.9%) patients. No device-related adverse events occurred, resulting in a 30-day device success rate of 91.9%. Compared with baseline, 30-day ankle brachial index (0.66+/-0.24 versus 0.89+/-0.20; P<0.001) and Rutherford class (3 [2, 4] versus 0 [0, 1], P<0.001) significantly improved. CONCLUSIONS: The SoundBiteTM Active Wire Crossing System feasibility study demonstrates a favorable safety and efficacy profile for the SoundBiteTM Active Wire in infrainguinal CTOs. PMID- 29790722 TI - Minimally invasive endoscopic-assisted approaches to the posterior fossa. AB - Modern surgical approaches are becoming more minimalistic, associated with the term 'minimally invasive'. The endoscope provides a more panoramic anatomical view in addition to the ability to access narrow deep corners with decent illumination and clear visualization. Endoscopic assisted microsurgery through a tailored small craniotomy is the foundation of keyhole surgery. The endoscope can be advanced deeper into the field, thus enhancing an exposure and allowing bimanual dissection, thus prompting smaller craniotomies and tailored key exposures. The term 'minimally invasive' became associated with reduction of overall tissue injury, decreased potential complications, reduced recovery times/hospital stay, and overall reduced costs. This minimally invasive concept became successfully applicable to diverse pathologies in the three cranial fossae. The posterior fossa, houses the most critical neurovascular structures of the brain in an intricate and complex anatomical organization. In this manuscript, we describe keyhole endoscopic-assisted approaches to different regions of the posterior fossa. Five corridors for these approaches are described: 1. Midline supracerebellar- infratentorial to the pineal region, 2. Upper cerebellopontine angle (CPA) to the trigeminal region, 3. Middle cerebellopontine angle to the vestibulocochlear region and internal auditory meatus, 4. Inferior cerebellopontine angle to the jugular foramen region and lower cranial nerves, and 5. Midline infracerebellar to posterior foramen magnum and the craniocervical junction. We then present a general review of the published literature and case examples demonstrating the effectiveness of the endoscopic-assisted keyhole concept. PMID- 29790723 TI - Training the skull base surgeon of the future: a comprehensive approach. AB - The tremendous advances in endoscopic skull base surgery added new a set of intricate less invasive approaches to the neurosurgical armamentarium. The new generations of neurosurgeons face the challenge of adopting the ever-changing technology and quickly learning modern surgical techniques beyond the traditional neurosurgery comfort zone. The future skull base surgeon must be well trained and knowledgeable in all surgical portals to the skull base in order to select the safest least invasive, most direct approach that offers the optimum exposure to handle a complex skull base pathology. The multi portal/corridor philosophy is often adopted in order to achieve superior surgical and clinical outcomes. Neurosurgeons need to consider such an approach when appropriate as it may offer a superior outcome while minimizing the morbidity associated with large exposures. PMID- 29790724 TI - Neuroprotection in traumatic brain injury. AB - Traumatic brain injury (TBI) has a high incidence worldwide and is associated with significant morbidity and mortality. TBI has enduring implications in several domains and limits overall quality of life even in the survivors. Assessment of failures of different strategies attempted at improving outcomes in traumatic brain injury is required. Several neuroprotective strategies have been studied to limit the morbidity and mortality associated with TBI. Various approaches, both pharmacologic and surgical, have been tried. In this article, we will review the epidemiology of TBI, the impact of secondary brain injury on outcomes and different strategies in traumatic brain injury. Furthermore, discussion into failure of different strategies and necessary future approach will be discussed. TBI remains a challenging condition to intervene on due to its heterogeneity. Future work should incorporate a multi-disciplinary as well as multi-center approach to target specific subset of patient population. PMID- 29790725 TI - The utilization of fluorescein in brain tumor surgery: a systematic review. AB - INTRODUCTION: Sodium Fluorescein (SF) is a green, water-soluble dye with the capacity to accumulate in cerebral areas as a result of damaged blood-brain barrier (BBB); this property allows SF to concentrate specifically at the tumor site of various types of brain neoplasms, making the tumor tissue more clearly visible. EVIDENCE ACQUISITION: A literature search (1947-2018) was conducted with the keywords "fluorescein neurosurgery", "YELLOW neurosurgery", "fluorescein brain tumor", "YELLOW brain tumor". We included clinical studies, clinical trials, observational studies, only conducted on humans and concerning surgery; in addition, we have included 3 articles derived from the analysis of the references of other papers. Ultimately, 57 articles were included for further analysis. EVIDENCE SYNTHESIS: Fluorescein as a fluorescent tracer in neuro oncology is gaining a wider acceptance in the neurosurgical literature: until February 1st, 2018, at least 1099 neuro-oncological patients have been operated through fluorescein-assistance, mostly only after 2012. The most important application remains the aim to improve tumor visualization and extent of resection for high-grade gliomas (HGG), but the nonspecific mechanism of action is the theoretical base for its use also for tumors different from HGG. Nevertheless, no homogenous protocol of fluorescein utilization in neurosurgical oncology can be found in literature. CONCLUSIONS: Fluorescein-guided surgery is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration, with a growing evidence-based background. PMID- 29790726 TI - Minimally invasive approaches to craniosynostosis. AB - Craniosynostosis (CS) is defined as the premature fusion of one or more calvarial sutures. This carries several consequences, including abnormal/asymmetric cranial vault development, increased intracranial pressure, compromised neurocognitive development, and craniofacial deformity. Definitive management is surgical with the goal of protecting cerebral development by re-establishing normal cranial vault expansion and correcting cosmetic deformity. In today's practice, CS surgery has advanced radically from simple craniectomies to major cranial vault reconstructive (CVR) procedures. More recently there has been considerable interest in endoscopic assisted surgery (EAS). Theoretical benefits include decreased operative time, morbidity, blood loss, postoperative pain, cost and faster recovery times. In this focused review, we summarize the current body of literature reporting clinical outcomes in EAS and review the data comparing EAS and CVR. PMID- 29790727 TI - Pathophysiology of severe traumatic brain injury. AB - Traumatic brain injury is a leading cause of morbidity and mortality globally, particularly among young people, with significant social and economic effects. The World Health Organization (WHO) estimates that more than five million people die each year from traumatic injuries worldwide. While public health initiatives such as seatbelts and airbags have had a major impact, it will be impossible to prevent traumatic brain injury.Therefore, it is important that we understand the pathophysiology of secondary brain injury to be able to effectively treat our patient and also to develop novel targets of future interventions. The mechanisms of secondary brain injury are complex involving alterations in cerebral perfusion, activation of inflammatory cytokines and excitotoxicity. While our understanding of these mechanisms has advanced greatly over the last decade, there is still much to learn and great uncertainty at the bedside. There has been some recent success with the discovery of some simple interventions that can reduce secondary brain injury and improve outcomes in patients after traumatic brain injury. In this review we summarize the current understanding of mechanisms and pathophysiology of primary and secondary brain injury, the goals for current treatment and potential targets for future therapy. PMID- 29790728 TI - Hydroxylated Polybrominated Biphenyl Ethers Exert Estrogenic Effects via Non Genomic G Protein-Coupled Estrogen Receptor Mediated Pathways. AB - BACKGROUND: Numerous studies have indicated the estrogenic effects of polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs (OH-PBDEs). However, the previous mechanistic studies focused on their estrogenic effects through genomic transcriptional activation of estrogen receptors. OBJECTIVE: The present study aimed to investigate the estrogenic effects of PBDEs and OH-PBDEs via nongenomic G protein-coupled estrogen receptor (GPER) pathways. METHODS: The binding affinities of 12 PBDEs and 18 OH-PBDEs with GPER were determined by a fluorescence competitive binding assay in a human breast cancer cell line (SKBR3). Molecular docking was performed to simulate the interactions. Their activities on GPER pathways were investigated by detecting calcium mobilization and cyclic adenosine monophosphate (cAMP) accumulation in SKBR3 cells. The effects on SKBR3 cell migration were investigated using Boyden chamber and wound healing assays. RESULTS: Our results showed that 11 of the OH-PBDEs but none of the PBDEs bound to GPER directly. Relative binding affinities ranged from 1.3% to 20.0% compared to 17beta-estradiol. Docking results suggested that the hydroxyl group played an essential role in the binding of OH-PBDEs to GPER by forming hydrogen bond interactions. Most of the OH-PBDEs activated subsequent GPER signaling pathways. Among them, 4'-OH-BDE-049, 5'-OH-BDE-099, and 3'-OH-BDE-154 displayed the highest activity with lowest effective concentrations (LOECs) of 10 100 nM. These three OH-PBDEs also promoted SKBR3 cell migration via GPER pathways with LOECs of 0.1-1 MUM. CONCLUSION: OH-PBDEs could bind to GPER, activate the subsequent signaling pathways, and promote SKBR3 cell migration via GPER pathways. OH-PBDEs might exert estrogenic effects by a novel nongenomic mechanism involving the activation of GPER at nanomolar concentrations. https://doi.org/10.1289/EHP2387. PMID- 29790730 TI - Energy-Saving Synthesis of MOF-Derived Hierarchical and Hollow Co(VO3)2-Co(OH)2 Composite Leaf Arrays for Supercapacitor Electrode Materials. AB - A one-step and energy-saving method was proposed to synthesize hierarchical and hollow Co(VO3)2-Co(OH)2 composite leaf arrays on carbon cloth, which expressed high capacitance (522 mF cm-2 or 803 F g-1 at the current density of 0.5 mA cm 2), good rate capability (79.5% capacitance retention after a 30-fold increase of the current density) and excellent cycling stability (90% capacitance retention after 15 000 charge-discharge cycles) when tested as a supercapacitor electrode. PMID- 29790731 TI - Electrochemical Properties of the LiNi0.6Co0.2Mn0.2O2 Cathode Material Modified by Lithium Tungstate under High Voltage. AB - An amount (5 wt %) of lithium tungstate (Li2WO4) as an additive significantly improves the cycle and rate performances of the LiNi0.6Co0.2Mn0.2O2 electrode at the cutoff voltage of 4.6 V. The 5 wt % Li2WO4-mixed LiNi0.6Co0.2Mn0.2O2 electrode delivers a reversible capacity of 199.2 mA h g-1 and keeps 73.1% capacity for 200 cycles at 1 C. It retains 67.4% capacity after 200 cycles at 2 C and delivers a discharge capacity of 167.3 mA h g-1 at 10 C, while those of the pristine electrode are only 44.7% and 87.5 mA h g-1, respectively. It is shown that the structure of the LiNi0.6Co0.2Mn0.2O2 cathode material is not affected by mixing Li2WO4. The introduced Li2WO4 effectively restrains the LiPF6 and carbonate solvent decomposition by consuming PF5 at high cutoff voltage, forming a stable cathode/electrolyte interface film with low resistance. PMID- 29790732 TI - Proton-Controlled Organic Microlaser Switch. AB - Microscale laser switches have been playing irreplaceable roles in the development of photonic devices with high integration levels. However, it remains a challenge to switch the lasing wavelengths across a wide range due to relatively fixed energy bands in traditional semiconductors. Here, we report a strategy to switch the lasing wavelengths among multiple states based on a proton controlled intramolecular charge-transfer (ICT) process in organic dye-doped flexible microsphere resonant cavities. The protonic acids can effectively bind onto the ICT molecules, which thus enhance the ICT strength of the dyes and lead to a red-shifted gain behavior. On this basis, the gain region was effectively modulated by using acids with different proton-donating ability, and as a result, laser switching among multiple wavelengths was achieved. The results will provide guidance for the rational design of miniaturized lasers with performances based on the characteristic of organic optoelectronic materials. PMID- 29790733 TI - Mechanically Robust Gels Formed from Hydrophobized Cellulose Nanocrystals. AB - Cellulose nanocrystals (CNCs) that bind to each other through associative hydrophobic interactions have been synthesized by modifying sulfated CNCs (sCNCs) with hydrophobic moieties. These octyl-CNCs form gels at significantly lower concentrations than parent sCNCs, producing extremely strong hydrogels. Unlike sCNCs, these octyl-CNCs do not form ordered liquid crystalline phases indicating a random association into a robust network driven by hydrophobic interactions. Furthermore, involvement of the octyl-CNCs into multicomponent supramolecular assembly was demonstrated in combination with starch. AFM studies confirm favorable interactions between starch and octyl-CNCs, which is thought to be the source of the dramatic increase in gel strength. PMID- 29790729 TI - Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort. AB - BACKGROUND: There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype. OBJECTIVES: We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008. METHODS: Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained. RESULTS: In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (?DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of ?DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ?DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery. CONCLUSIONS: In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. https://doi.org/10.1289/EHP2358. PMID- 29790734 TI - Palladium Supported on an Amphiphilic Triazine-Urea-Functionalized Porous Organic Polymer as a Highly Efficient Electrocatalyst for Electrochemical Sensing of Rutin in Human Plasma. AB - Metal nanoparticle-containing porous organic polymers have gained great interest in chemical and pharmaceutical applications owing to their high reactivity and good recyclability. In the present work, a palladium nanoparticle-decorated triazine-urea-based porous organic polymer (Pd@TU-POP) was designed and synthesized using 1,3-bis(4-aminophenyl)urea with cyanuric chloride and palladium acetate. The porous structure and physicochemical properties of the electrode material Pd@TU-POP were observed using a range of standard techniques. The Pd@TU POP material on the electrode surface showed superior sensing ability for rutin (RT) because the Pd dispersion facilitated the electrocatalytic performance of TU POP by reducing the overpotential of RT oxidation dramatically and improving the stability significantly. Furthermore, TU-POP provides excellent structural features for loading Pd nanoparticles, and the resulting Pd@TU-POP exhibited enhanced electron transfer and outstanding sensing capability in a linear range between 2 and 200 pM having a low detection value of 5.92 * 10-12 M (S/N = 3). The abundant porous structure of Pd@TU-POP not only provides electron transport channels for RT diffusion but also offers a facile route for quantification sensing of RT with satisfactory recoveries in aqueous electrolyte containing human plasma and red wine. These data reveal that the synthetic Pd@TU-POP is an excellent potential platform for the detection of RT in biological samples. PMID- 29790737 TI - Environmental Stability of Plasmonic Biosensors Based on Natural versus Artificial Antibody. AB - Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are considered to be highly promising for on chip and point-of-care biodiagnostics. However, most of the current plasmonic biosensors employ natural antibodies as biorecognition elements, which can easily lose their biorecognition ability upon exposure to environmental stressors (e.g., temperature and humidity). Plasmonic biosensors relying on molecular imprints as recognition elements (artificial antibodies) are hypothesized to be an attractive alternative for applications in resource-limited settings due to their excellent thermal, chemical, and environmental stability. In this work, we provide a comprehensive comparison of the stability of plasmonic biosensors based on natural and artificial antibodies. Although the natural antibody-based plasmonic biosensors exhibit superior sensitivity, their stability (temporal, thermal, and chemical) was found to be vastly inferior to those based on artificial antibodies. Our results convincingly demonstrate that these novel classes of artificial antibody-based plasmonic biosensors are highly attractive for point-of care and resource-limited conditions where tight control over transport, storage, and handling conditions is not possible. PMID- 29790736 TI - Desymmetrization of meso-Dibromocycloalkenes through Copper(I)-Catalyzed Asymmetric Allylic Substitution with Organolithium Reagents. AB - The highly regio- and enantioselective (up to >99:1 dr, up to 99:1 er) desymmetrization of meso-1,4-dibromocycloalk-2-enes using asymmetric allylic substitution with organolithium reagents to afford enantioenriched bromocycloalkenes (ring size of 5 to 7) has been achieved. The cycloheptene products undergo an unusual ring contraction. The synthetic versatility of this Cu(I)-catalyzed reaction is demonstrated by the concise stereocontrolled preparation of cyclic amino alcohols, which are privileged chiral structures in natural products and pharmaceuticals and widely used in synthesis and catalysis. PMID- 29790735 TI - Sensing DNA through DNA Charge Transport. AB - DNA charge transport chemistry involves the migration of charge over long molecular distances through the aromatic base pair stack within the DNA helix. This migration depends upon the intimate coupling of bases stacked one with another, and hence any perturbation in that stacking, through base modifications or protein binding, can be sensed electrically. In this review, we describe the many ways DNA charge transport chemistry has been utilized to sense changes in DNA, including the presence of lesions, mismatches, DNA-binding proteins, protein activity, and even reactions under weak magnetic fields. Charge transport chemistry is remarkable in its ability to sense the integrity of DNA. PMID- 29790738 TI - Design and Development of Polysaccharide-Doxorubicin-Peptide Bioconjugates for Dual Synergistic Effects of Integrin-Targeted and Cell-Penetrating Peptides for Cancer Chemotherapy. AB - Polymer-drug conjugation is an attractive approach for target delivering insoluble and highly toxic drugs to tumor sites to overcome the side-effects caused by cancer chemotherapy. In this study we designed and synthesized novel polymer-drug-peptide conjugates for improved specificity on targeting cancer cells. Chemically modified polysaccharide, carboxymethylcellulose (CMC), was conjugated with doxorubicin (DOX) anticancer drug by amide bonds and dually biofunctionalized with integrin-target receptor tripeptide (RGD) and l-arginine (R) as cell-penetrating amino acid for synergistic targeting and enhancing internalization by cancer cells. These bioconjugates were tested as prodrugs against bone, breast, and brain cancer cell lines (SAOS, MCF7, and U87) and a normal cell line (HEK 293T, reference). The physicochemical characterization showed the formation of amide bonds between carboxylates (-RCOO-) from CMC biopolymer and amino groups (-NH2) from DOX and peptides (RGD or R). Moreover, these polymer-drug-peptide bioconjugates formed nanoparticulate colloidal structures and behaved as "smart" drug delivery systems (DDS) promoting remarkable reduction of the cytotoxicity toward normal cells (HEK 293T) while retaining high killing activity against cancer cells. Based on cell viability bioassays, DNA-staining, and confocal laser microscopy, this effect was assigned to the association of physicochemical aspects with the difference of the endocytic pathways and the drug release rates in live cells caused by the biofunctionalization of the macromolecule-drug systems with RGD and l-arginine. In addition, chick chorioallantoic membrane (CAM) assay was performed as an in vivo xenograft model test, which endorsed the in vitro results of anticancer activities of these polymer-drug systems. Thus, prodrug nanocarriers based on CMC DOX-peptide bioconjugates were developed for simultaneously integrin-targeting and high killing efficacy against cancer cells, while preserving healthy cells with promising perspectives in cancer chemotherapy. PMID- 29790739 TI - Universal Coatings Based on Zwitterionic-Dopamine Copolymer Microgels. AB - Multifunctional coatings that adhere to chemically distinct substrates are vital in many industries, including automotive, aerospace, shipbuilding, construction, petrochemical, biomedical, and pharmaceutical. We design well-defined, nearly monodisperse microgels that integrate hydrophobic dopamine methacrylamide monomers and hydrophilic zwitterionic monomers. The dopamine functionalities operate as both intraparticle cross-linkers and interfacial binders, respectively providing mechanical strength of the coatings and their strong adhesion to different substrates. In tandem, the zwitterionic moieties enable surface hydration to empower antifouling and antifogging properties. Drop-casting of microgel suspensions in ambient as well as humid environments facilitates rapid film formation and tunable roughness through regulation of cross-linking density and deposition conditions. PMID- 29790741 TI - Entrapment of Prostate Cancer Circulating Tumor Cells with a Sequential Size Based Microfluidic Chip. AB - Circulating tumor cells (CTCs) are broadly accepted as an indicator for early cancer diagnosis and disease severity. However, there is currently no reliable method available to capture and enumerate all CTCs as most systems require either an initial CTC isolation or antibody-based capture for CTC enumeration. Many size based CTC detection and isolation microfluidic platforms have been presented in the past few years. Here we describe a new size-based, multiple-row cancer cell entrapment device that captured LNCaP-C4-2 prostate cancer cells with >95% efficiency when in spiked mouse whole blood at ~50 cells/mL. The capture ratio and capture limit on each row was optimized and it was determined that trapping chambers with five or six rows of micro constriction channels were needed to attain a capture ratio >95%. The device was operated under a constant pressure mode at the inlet for blood samples which created a uniform pressure differential across all the microchannels in this array. When the cancer cells deformed in the constriction channel, the blood flow temporarily slowed down. Once inside the trapping chamber, the cancer cells recovered their original shape after the deformation created by their passage through the constriction channel. The CTCs reached the cavity region of the trapping chamber, such that the blood flow in the constriction channel resumed. On the basis of this principle, the CTCs will be captured by this high-throughput entrapment chip (CTC-HTECH), thus confirming the potential for our CTC-HTECH to be used for early stage CTC enrichment and entrapment for clinical diagnosis using liquid biopsies. PMID- 29790740 TI - Organometallic Gold(III) Reagents for Cysteine Arylation. AB - An efficient method for chemoselective cysteine arylation of unprotected peptides and proteins using Au(III) organometallic complexes is reported. The bioconjugation reactions proceed rapidly (<5 min) at ambient temperature in various buffers and within a wide pH range (0.5-14). This approach provides access to a diverse array of S-aryl bioconjugates including fluorescent dye, complex drug molecule, affinity label, poly(ethylene glycol) tags, and a stapled peptide. A library of Au(III) arylation reagents can be prepared as air-stable, crystalline solids in one step from commercial reagents. The selective and efficient arylation procedures presented in this work broaden the synthetic scope of cysteine bioconjugation and serve as promising routes for the modification of complex biomolecules. PMID- 29790742 TI - Surface Modification of Silicon Nanoparticles by an "Ink" Layer for Advanced Lithium Ion Batteries. AB - Owing to its high specific capacity, silicon is considered as a promising anode material for lithium ion batteries (LIBs). However, the synthesis strategies for previous silicon-based anode materials with a delicate hierarchical structure are complicated or hazardous. Here, Prussian blue analogues (PBAs), widely used in ink, are deposited on the silicon nanoparticle surface (PBAs@Si-450) to modify silicon nanoparticles with transition metal atoms and a N-doped carbon layer. A facile and green synthesis procedure of PBAs@Si-450 nanocomposites was carried out in a coprecipitation process, combined with a thermal treatment process at 450 degrees C. As-prepared PBAs@Si-450 delivers a reversible charge capacity of 725.02 mAh g-1 at 0.42 A g-1 after 200 cycles. Moreover, this PBAs@Si-450 composite exhibits an exceptional rate performance of ~1203 and 263 mAh g-1 at current densities of 0.42 and 14 A g-1, respectively, and fully recovered to 1136 mAh g-1 with the current density returning to 0.42 A g-1. Such a novel architecture of PBAs@Si-450 via a facile fabrication process represents a promising candidate with a high-performance silicon-based anode for LIBs. PMID- 29790743 TI - Correction to "Identification of Different Bile Species and Fermentation Times of Bile Arisaema Based on an Intelligent Electronic Nose and Least Squares Support Vector Machine". PMID- 29790744 TI - Myristic Acid-Modified DA7R Peptide for Whole-Process Glioma-Targeted Drug Delivery. AB - The clinical treatment of aggressive glioma has been a great challenge, mainly because of the complexity of the glioma microenvironment and the existence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hampers the effective accumulation of most therapeutic agents in the glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis, and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma-targeted drug delivery strategy was proposed. The DA7R peptide has effective BBTB-penetrating and notable glioma-, angiogenesis-, and VM-targeting abilities. Herein, we designed a myristic acid modified DA7R ligand (MC-DA7R), which combines tumor-homing DA7R with BBB-penetrable MC. MC-DA7R was then immobilized to PEGylated liposomes (MC DA7R-LS) to form a whole-process glioma-targeting system. MC-DA7R-LS exhibited exceptional internalization in glioma, tumor neovascular, and brain capillary endothelial cells. Enhanced BBTB- and BBB-traversing efficiencies were also observed on MC-DA7R-LS. Ex vivo imaging on brain tumors also demonstrated the feasibility of MC-DA7R-LS in intracranial glioma-homing, whereas the immunofluorescence studies demonstrated its GSC and angiogenesis homing. Furthermore, doxorubicin-loaded MC-DA7R-LS accomplished a remarkable therapeutic outcome, as a result of a synergistic improvement on the glioma microenvironment. Our study highlights the potential of the MC-modified DA7R peptide as a great candidate for the whole-process glioma-targeted drug delivery. PMID- 29790745 TI - Vanillin-Ameliorated Development of Azoxymethane/Dextran Sodium Sulfate-Induced Murine Colorectal Cancer: The Involvement of Proteasome/Nuclear Factor kappaB/Mitogen-Activated Protein Kinase Pathways. AB - Vanillin is a natural dietary flavoring widely used in the food industry. Colorectal cancer (CRC) is one of the common malignancies in the world. Chronic intestinal inflammation is a risk factor for the development of CRC. We have previously found that vanillin improves and prevents colitis in mice. Here we evaluated the inhibitory activities of vanillin on a mouse model of colitis induced CRC. Mice were challenged intraperitoneally with azoxymethane (AOM) and orally with dextran sodium sulfate (DSS). Various dosages of vanillin were orally administered for 13 consecutive weeks. Vanillin alleviated the development of tumors in AOM/DSS-induced mice. The total number of tumors in 100 mg/kg vanillin group was significantly reduced by 57.14 +/- 7.67%, compared with sham group. Gene expression analysis showed that vanillin downregulated the expression levels of proteasome genes in colon tissues. Moreover, vanillin at 10 mM significantly suppressed proteasome activities in HCT-116 cells by 41.27 +/- 0.41%. Furthermore, vanillin diminished the phosphorylation of mitogen-activated protein kinases (MAPKs) and reduced the number of p65-positive cells, proliferating cells, and granulocytes in colon tissues with statistical significance. In conclusion, our data suggested that vanillin was a bioactive compound that ameliorated the development of AOM/DSS-induced colon cancer in mice. Moreover, the amelioration of vanillin might be associated with the downregulation of proteasome, nuclear factor-kappaB, and MAPK pathways. PMID- 29790746 TI - Neuroprotective Compound from an Endophytic Fungus, Colletotrichum sp. JS-0367. AB - Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death. PMID- 29790747 TI - Characterization of Potent Aroma Compounds in Preserved Egg Yolk by Gas Chromatography-Olfactometry, Quantitative Measurements, and Odor Activity Value. AB - To characterize potent odor-active compounds in preserved egg yolk (PEY), volatile compounds were isolated by headspace solid-phase microextraction and solvent-assisted flavor evaporation. Gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS) analyses identified a total of 53 odor-active compounds by comparing the odor characteristics, MS data, and retention indices with those of reference compounds. Twenty-seven odorants were detected in at least five isolates that were extracted and analyzed by the same method, and their flavor dilution (FD) factors, ranging from 1 to 2048, were measured by aroma extract dilution analysis (AEDA). To further determine their contribution to the overall aroma profile of PEY, 22 odorants with FD factors >=16 and GC-MS responses were quantitated, and their odor activity values (OAVs) were calculated. According to the OAV results, 19 odorants with OAVs >= 1 are the potent odorants that greatly contribute to the characteristic aroma of PEY. Nine compounds were identified for the first time: (E,Z)-2,6-nonadienal, (E)-2 nonenal, 2-methylbutanal, dimethyl disulfide, trimethylamine, methional, dimethyl trisulfide, diisopropyl disulfide, and diethyl disulfide. PMID- 29790748 TI - Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4- d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza Compounds. AB - Alkylation of 4-methoxy-1 H-pyrazolo[3,4- d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-methyl product 4-methoxy-2 methyl-2 H-pyrazolo[3,4- d]pyrimidine (3b) in an 8/1 ratio over N1-methyl product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient stimulated echo (PFG-STE) NMR defined the molecular weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO. PMID- 29790750 TI - Tandem One-Pot Approach To Access 1,2,3-Triazole-fused Isoindolines through Cu Catalyzed 1,6-Conjugate Addition of Me3SiN3 to p-Quinone Methides followed by Intramolecular Click Cycloaddition. AB - A Cu-catalyzed one-pot approach has been developed for the synthesis of 1,2,3 triazole-fused tricyclic heterocycles. This tandem approach actually involves the 1,6-conjugate addition of Me3SiN3 to o-alkynylated p-quinone methides followed by an intramolecular [3+2]-cycloaddition reaction. This protocol allowed us to access a wide range of 1,2,3-trazole-fused isoindoline derivatives in moderate to good yields. PMID- 29790749 TI - Anti-inflammatory Activity of 8-Hydroxydaidzein in LPS-Stimulated BV2 Microglial Cells via Activation of Nrf2-Antioxidant and Attenuation of Akt/NF-kappaB Inflammatory Signaling Pathways, as Well As Inhibition of COX-2 Activity. AB - It was demonstrated that isoflavones can cross the blood-brain barrier, making them desirable candidate agents for the prevention of neurological symptoms. 8 Hydroxydaidzein (8-OHD, 4',7,8-trihydoxyisoflavone) is an isoflavone found only in fermented soy food. Current results showed that 8-OHD inhibited LPS-stimulated production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, by inhibiting gene expression in BV2 microglial cells. Moreover, 8-OHD markedly quenched reactive oxygen species (ROS) and activated NF-E2-related factor 2 (Nrf2) so as to upregulate expression of Phase II enzymes, including heme oxygenase (HO)-1, NAD(P)H quinone dehydrogenase 1 (NQO1), and the modifier subunit of glutamate cysteine ligase (GCLM). 8-OHD also suppressed LPS-stimulated phosphorylation of Akt and NF-kappaB p65. The anti-inflammatory activity of 8-OHD was attenuated by the HO-1 inhibitor zinc protoporphyrin (Znpp) but augmented by the PI3K/Akt inhibitor LY294002. 8 OHD also diminished LPS-induced prostaglandin E2 (PGE2) production without affecting cyclooxygenase (COX)-2 expression. In vitro assay shows that 8-OHD displayed mixed-type inhibition of COX-2 with an IC50 of 8.9 +/- 1.2 MUM. These data suggest that the anti-inflammatory activity of 8-OHD may be associated with the activation of Nrf2/HO-1 and attenuation of Akt/NF-kappaB signaling pathways as well as inhibition of COX-2 enzyme activity. In conclusion, 8-OHD, a potent Nrf2 activator, Akt/NF-kappaB activation suppressor, and COX-2 enzyme inhibitor, may have health-promoting effects for mitigating microglia activation and preventing neuroinflammation. PMID- 29790751 TI - Fluorescence of Cyclopropenium Ion Derivatives. AB - The synthesis of cyclopropenium-substituted amino compounds and analysis of their photophysical properties is described. Systematic structural modifications of these derivatives lead to measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory (TD-DFT) calculations, the origin of these trends was traced to internal charge transfer (ICT) coupled with ensuing structural reorganization for select naphthalene functionalized derivatives. Associated with this structural reorganization was an inward gearing of the cyclopropenium ring and twisting of the peri-NMe2 group into coplanarity with the naphthalene ring system. Further, reinforcement of an intramolecular H-bond (IMHB) in the excited state of these derivatives alludes to the importance of photoinduced H-bonding in this new class of cyclopropenium based fluorophores. PMID- 29790752 TI - Experiment and Computational Study on the Regioselectivity of Nucleophilic Addition to Unsymmetrical p-Benzynes Derived from Bergman Cyclization of Enediynes. AB - The regioselectivity in addition of nucleophiles to the p-benzyne intermediates derived from unsymmetrical aza-substituted enediynes via Bergman cyclization was studied. Computational studies [using UB3LYP/6-31G(d,p) level of theory] suggest that the p-benzyne intermediate retains its similar electrophilic character at the two radical centers even under unsymmetrical electronic perturbation, thus supporting the predicted model of nucleophilic addition to p-benzyne proposed by Perrin and co-workers (Perrin et al. J. Am. Chem. Soc. 2007, 129, 4795-4799) and later by Alabugin and co-workers (Peterson et al. Eur. J. Org. Chem. 2013, 2013, 2505-2527). However, observed experimental results suggest that there was small but definite regioselectivity (~5-25%), the extent varying with the electronic nature of the substituents. Differential solvated halide ion concentrations around the vicinity of two radical centers arising due to surrounding surface electrostatic potential (computationally calculated) may be one of the possible factors for such selectivity in some of the examined p-benzynes. However, other complicated dynamical issues like the trajectory of the attacking nucleophile to the radical center which can be influenced by electronic and/or steric perturbation of starting enediyne conformation cannot be ruled out. The overall yield of the anionic addition was in the range of 80-99%. PMID- 29790753 TI - Target-Decoy-Based False Discovery Rate Estimation for Large-Scale Metabolite Identification. AB - Metabolite identification is a crucial step in mass spectrometry (MS)-based metabolomics. However, it is still challenging to assess the confidence of assigned metabolites. We report a novel method for estimating the false discovery rate (FDR) of metabolite assignment with a target-decoy strategy, in which the decoys are generated through violating the octet rule of chemistry by adding small odd numbers of hydrogen atoms. The target-decoy strategy was integrated into JUMPm, an automated metabolite identification pipeline for large-scale MS analysis and was also evaluated with two other metabolomics tools, mzMatch and MZmine 2. The reliability of FDR calculation was examined by false data sets, which were simulated by altering MS1 or MS2 spectra. Finally, we used the JUMPm pipeline coupled to the target-decoy strategy to process unlabeled and stable isotope-labeled metabolomic data sets. The results demonstrate that the target decoy strategy is a simple and effective method for evaluating the confidence of high-throughput metabolite identification. PMID- 29790755 TI - Incrementing Stokes Shifts through the Formation of 2,2'-Biimidazoldiium Salts. AB - The formation of biimidazoldiium structures by the introduction of methyl substituents on the N atoms at the 3 and 3' positions of 2,2'-biimidazoles led to increments in the Stokes shift of these structures. Based on time-dependent density functional theory (TDDFT) calculations, the imidazolium rings become distorted and the N atoms of the imidazolium rings underwent structural changes through sp2 to sp3 rehybridization in the excited states. PMID- 29790754 TI - EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data. AB - Epigenetics has become a fundamental scientific discipline with various implications for biology and medicine. Epigenetic marks, mostly DNA methylation and histone post-translational modifications (PTMs), play important roles in chromatin structure and function. Accurate quantification of these marks is an ongoing challenge due to the variety of modifications and their wide dynamic range of abundance. Here we present EpiProfile 2.0, an extended version of our 2015 software (v1.0), for accurate quantification of histone peptides based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. EpiProfile 2.0 is now optimized for data-independent acquisition through the use of precursor and fragment extracted ion chromatography to accurately determine the chromatographic profile and to discriminate isobaric forms of peptides. The software uses an intelligent retention time prediction trained on the analyzed samples to enable accurate peak detection. EpiProfile 2.0 supports label-free and isotopic labeling, different organisms, known sequence mutations in diseases, different derivatization strategies, and unusual PTMs (such as acyl-derived modifications). In summary, EpiProfile 2.0 is a universal and accurate platform for the quantification of histone marks via LC-MS/MS. Being the first software of its kind, we anticipate that EpiProfile 2.0 will play a fundamental role in epigenetic studies relevant to biology and translational medicine. EpiProfile is freely available at https://github.com/zfyuan/EpiProfile2.0_Family . PMID- 29790757 TI - Cyclic Anion-Responsive pi-Electronic Molecules That Overcome Energy Losses Induced by Conformation Changes. AB - Preorganized structures suitable for anion binding were prepared by introducing dipyrrolyldiketone BF2 complexes as acyclic anion-responsive pi-electronic molecules into macrocycles. Pyrrole-inverted conformations, which typically present low stability in the case of acyclic derivatives, were obtained by covalent linkages through ring-closing olefin metathesis, exhibiting extremely high affinity for different anions. PMID- 29790756 TI - Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B. AB - A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity. PMID- 29790758 TI - Rhodium-Catalyzed Asymmetric Dearomative [4 + 3]-Cycloaddition of Vinylindoles with Vinyldiazoacetates: Access to Cyclohepta[ b]indoles. AB - A rhodium-catalyzed enantioselective formal [4 + 3]-cycloaddition of vinylindoles with vinyldiazoacetates has been developed, affording the dearomative cyclization products containing a newly formed seven-membered ring in up to 99% ee. Rh2( S DOSP)4 has been proven to be the best catalyst for the cycloaddition of 3 vinylindoles with vinyldiazoacetates, whereas Rh2( S-TCPTTL)4 has enhanced the enantioselectivity for 2-vinylindoles. PMID- 29790760 TI - Copper-Catalyzed Dehydrogenative Diels-Alder Reaction. AB - A practical and effective copper-catalyzed dehydrogenative Diels-Alder reaction of gem-diesters and ketone with dienes has been established. The active dienophiles were generated in situ via a radical-based dehydrogenation process, which reacted with a wide variety of dienes to afford various polysubstituted cyclohexene derivatives in good to excellent yields. PMID- 29790759 TI - Cyclization of Ketones with Nitriles under Base: A General and Economical Synthesis of Pyrimidines. AB - A facile, general, and economical synthesis of diversely functionalized pyrimidines has been realized under basic conditions via the copper-catalyzed cyclization of ketones with nitriles. The reaction proceeds via a novel pathway involving the nitriles acting as electrophiles and consecutive C-C bond and two C N bond formations and shows broad substrate scope and good tolerance of many important functional groups. This strategy represents a new platform for constructing pyrimidine structures. PMID- 29790761 TI - Selectivity Controlled Palladium-Catalyzed Carbonylative Synthesis of Propiolates and Chromenones from Phenols and Alkynes. AB - An interesting selectivity-controlled palladium-catalyzed oxidative carbonylation procedure for the synthesis of propiolates and chromenones has been developed. Starting from phenols and alkynes, under slightly different conditions, various propiolates and chromenones can be isolated in moderate to good yields. Additionally, this also presents the first example of direct carbonylative annulation of nonpreactivated phenols and terminal alkynes to produce chromenones. PMID- 29790762 TI - Reagent-Controlled Synthesis of the Branched Trisaccharide Fragment of the Antibiotic Saccharomicin B. AB - A concise synthesis of a branched trisaccharide, alpha-l-Dig-(1 -> 3)-[alpha-l Eva-(1 -> 4)]-beta-d-Fuc, corresponding to saccharomicin B, has been developed via reagent-controlled alpha-selective glycosylations. Starting from the d-fucose acceptor, l- epi-vancosamine was selectively installed using 2,3-bis(2,3,4 trimethoxyphenyl)cyclopropene-1-thione/oxalyl bromide mediated dehydrative glycosylation. Following deprotection, l-digitoxose was installed using the AgPF6/TTBP thioether-activation method to produce the trisaccharide as a single alpha-anomer. This highly functionalized trisaccharide can potentially serve as both a donor and an acceptor for the total synthesis of the antibiotic saccharomicin B. PMID- 29790763 TI - Decarbonylative Coupling of alpha-Keto Acids and Ynamides for Synthesis of beta Keto Imides. AB - A novel decarbonylative coupling of alpha-keto acids and ynamides with extrusion of CO for synthesis of beta-keto imides is reported. This process features mild reaction conditions, a broad substrate scope, and high efficiency. An isotope labeling reaction and GC analysis were conducted to elucidate a plausible reaction mechanism. PMID- 29790764 TI - C-Me Bond Formation at All Methylene Bridges of the Calix[4]arene Scaffold. AB - A reaction of a distal dibromo diketocalix[4]arene with excess MeLi, followed by acid-catalyzed dehydration, yields a derivative with a pair of opposite exocyclic double bonds, and a pair of trans methyl groups at the bridges. A reaction of a tetrabromo calix[4]arene derivative with excess MeLi yields a calix[4]arene derivative with all methylene bridges monomethylated in all- cis fashion. PMID- 29790765 TI - Metal Template Assisted Proximal Arrangement of a Nucleophile and an Electrophile: Site-Selective Acylation of alpha-Hydroxyamides in Polyols. AB - Site-selective acylation of alpha-hydroxyl groups in amides has been achieved in the presence of other primary hydroxyl groups with intrinsic high reactivity. In this methodology, a relatively stable pyridine aldoxime ester was exploited as an acyl donor to suppress undesired acylation. The catalytic activation of a pyridine aldoxime ester with a Lewis acid produced a cationic complex, which preferentially attracted the Lewis basic alpha-hydroxyamide via a template effect, to thus facilitate o-acylation. PMID- 29790766 TI - Tetraphenylethylenepyrrolo[3,2- b]pyrrole Hybrids as Solid-State Emitters: The Role of Substitution Pattern. AB - Two hybrid dyes possessing tetraphenylethylene moieties weakly conjugated with a pyrrolo[3,2- b]pyrrole core have been synthesized. Both dyes display a weak emission in solution, however, in the solid state a ~100-fold increase in the fluorescence quantum yield is observed. The position of the molecular rotors about the core greatly influences the photophysical characteristics. The variances in emission properties were assigned to entirely different changes in dihedral angles upon excitation, which in turn have substantial effects on radiative rate constants, allowed transitions, and HOMO/LUMO distribution. PMID- 29790767 TI - Copper-Promoted 6- endo-trig Cyclization of beta,gamma-Unsaturated Hydrazones for the Synthesis of 1,6-Dihydropyridazines. AB - A novel and efficient strategy for the synthesis of 1,6-dihydropyridazines via copper-promoted 6- endo-trig cyclization of readily available beta,gamma unsaturated hydrazones have been developed. A series of 1,6-dihydropyridazines have been synthesized by this method with good yields, high functional group tolerance, and remarkable regioselectivity under mild conditions. Importantly, the 1,6-dihydropyridazines can be efficiently converted to biologically important pyridazines in the presence of NaOH. PMID- 29790768 TI - Trapping of N-Acyliminium Ions with Enamides: An Approach to Medium-Sized Diaza Heterocycles. AB - Enamides equipped with N-acyliminium ion precursors were obtained through reduction of ynamides tethered to N-imides. Intramolecular TMSOTf-mediated trapping of N-acyliminium ions provided a variety of polyfunctionalized medium sized diaza-heterocycles of putative pharmacological interest. PMID- 29790769 TI - Synthesis of 1,2,3-Triazines Using the Base-Mediated Cyclization of ( Z)-2,4 Diazido-2-alkenoates. AB - A highly efficient and convenient method for the synthesis of 6-aryl-1,2,3 triazine-4-carboxylate esters has been developed using readily accessible ( Z)-4 aryl-2,4-diazido-2-alkenoates. This reaction is performed under mildly basic conditions without the assistance of any transition metals or strong acid. PMID- 29790771 TI - Child abuse: Awareness is the first step to action. AB - Most of the physical injuries that children are subjected to affect the head and neck region; approximately 50% of injuries due to child abuse occur in the orofacial region and almost 15% of these injuries are confined to the head region (Cairns A.M.). For this reason, the dental team has a key role in identifying and detecting child abuse. In addition, having paediatric dentists an ongoing relationship with their young patients and families give them the opportunity to observe and assess not only the physical and psychological condition of the children, but also the family environment (the majority of abuse cases toward children are from the caregiver or the parents). These types of lesions could be confused with occasional children traumatic injuries, and this is why dentist should be trained to detect the signs of child abuse, as well be informed on how these cases should be reported to authorities. In a recent research about child abuse in the United Arab Emirates-UAE (H. Al Hajeri et al. Assessment of the knowledge of United Arab Emirates dentists of child maltreatment, protection and safeguarding) more than half of the respondents (54.6%) were not aware of such guidelines/procedures. According to the authors, the main factors affecting the decision of reporting were the lack of knowledge on the appropriate reporting procedure (60%), and the fear of family retaliation toward the child (59%). The Arab colleagues rightly concluded: "diagnosis is a shared responsibility of the child protection team and no matter what obstacles and fears the dentist may have; the main priority is the child". More efforts should be made to improve knowledge, attitude and practice of dentists in this social problem in order to decrease child abuse worldwide. PMID- 29790770 TI - Multicomponent Synthesis and Binding Mode of Imidazo[1,2- a]pyridine-Capped Selective HDAC6 Inhibitors. AB - The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode. PMID- 29790772 TI - Influence of occlusal characteristics, food intake and oral hygiene habits on dental caries in adolescents: a cross-sectional study. AB - AIM: Dental caries is one of the most common oral diseases affecting children. The complex multifactorial aetiology of caries involves host (saliva composition and tooth enamel characteristics), oral microflora and substrate (oral hygiene quality and dietary habits composition). Occlusal characteristics may be also a factor in dental caries development. The aim of this aepidemiologic study was to verify the association between DMFT (Decayed, Missed, Filled Teeth) index and occlusal characteristics, dietary habits, oral hygiene habits and parents' education level in a sample of 12-year-old schoolchildren from Southern Italy. MATERIALS AND METHODS: A sample of 536 children was examined to detect dental caries status and several occlusal variables (i.e. molar relationship, overjet and overbite, presence of crossbite, scissor bite, crowding, diastemas and/or midline deviation). A questionnaire to retrieve parents' educational level, patient's dietary and oral hygiene habits was administered. The associations among these variables were assessed statistically through the ?2 test. RESULTS: A positive association was found between caries, parents' social status and some occlusal disorders. va specificato, l'abstract non puo essere una caccia al tesoro. In relation to occlusal variables, crossbite (?2=3.96, P=0.04) was significantly associated to caries. A significant association was also found between the education level of mothers (?2=7.74, P<0.01) and fathers (?2=6.35, P=0.01) and the presence of caries. Dietary habits, oral hygiene and remaining occlusal characteristics were not associated with caries presence (all P>0.05). CONCLUSIONS: Of the evaluated occlusal characteristics only posterior crossbite was associated with caries prevalence. Education level of the parents was the other factor significantly associated with caries. Dietary habits, oral hygiene frequency and the remaining occlusal characteristics were not associated with dental caries. PMID- 29790773 TI - Decisions on repositioning of intruded permanent incisors; a review and case presentation. AB - BACKGROUND: Traumatic intrusion is a luxation type of injury where the tooth is displaced along the axis of the tooth, into the alveolus. This injury is regarded as serious because of the tissue damage that it causes. The traumatic movement is associated with severe damage to the periodontal ligament, pulpal tissue, root and alveolar socket. Despite its severity, the rare occurrence of this injury in permanent teeth has resulted in limited studies of immature and mature permanent incisors. The purpose of this paper is to review this luxation injury of permanent immature incisors, and to describe its diagnosis, treatment and management. In particular, we describe the repositioning strategies used in cases of intrusion injury. These include (i) monitoring spontaneous re-eruption, (ii) active orthodontic repositioning and (iii) surgical repositioning. Firstly, monitoring spontaneous re-eruption is observing and waiting for the intruded tooth to return to its original position. This process is not a normal developmental eruption and the outcome is not always predictable, nor is the time needed for this to happen. Secondly, active orthodontic repositioning is used to describe the process of rapidly moving the intruded tooth to its original position with the aid of an orthodontic appliance. Active orthodontic repositioning is often misunderstood as normal orthodontic movement. Orthodontic movement allows for periodontal ligament remodelling, using light intermittent forces. In contrast the active orthodontic repositioning used to move intruded incisors is rapid, and the primary aim is to achieve correct tooth position as rapidly as possible. Thirdly, surgical repositioning uses surgical intervention to bring the tooth back to its original position. A case of an intruded immature permanent incisor is presented, with a particular emphasis on these critical decisions on repositioning and showing the use of the three modalities of treatment in sequence, in order to achieve an outcome. PMID- 29790774 TI - Assessment of the knowledge of United Arab Emirates dentists of Child Maltreatment, protection and safeguarding. AB - AIM: Child safeguarding is society's responsibility. Dentists are uniquely positioned to recognise Child Abuse and Neglect (CAN) in dental practice and the wider society. The United Arab Emirates (UAE) introduced a child protection law in 2016. We aimed to assess the awareness of UAE dentists of child maltreatment, protection and safeguarding. Study Design A cross-sectional survey. MATERIALS AND METHODS: We surveyed 381 UAE dentists about the knowledge and practice of CAN and safeguarding issues using a self-administered anonymous questionnaire. Statistical analysis was carried out using Chi-square, t-test, ANOVA and Pearson's correlation test and statistical significance was set as p <0.05. RESULTS: Over 39 % (n=152) of the responders suspected CAN; male dentists suspected more CAN than females (p=0.015). Orthodontists, paediatric dentists (p<0.001) and female dentists (p=0.001) were more knowledgeable about diagnosing CAN. Paediatric dentists attended more CAN-related postgraduate training (p<0.001) than other specialties. Over 90% (n=346) believed that CAN should be addressed, 58.1% (n=224) and 54.1% (n=206) had CAN undergraduate and postgraduate training respectively but 53.5% (n=204) were unaware of local child protection guidelines. Dentists barriers to child protection reporting were; fear of family violence (59.6%, n=227), lack of knowledge of referral process (60.2%, n=228) and lack of diagnosis certainty (54.9%, n=206). UAE dentists qualified in Western and Asian countries had fewer barriers for child protection reporting (p=0.022) than the Arab and Gulf Cooperation Council qualified dentists. CONCLUSIONS: A large minority of UAE dentists suspected CAN. Factors influencing child protection reporting were identified. Dentists' gender, specialty, and country of qualification affected their knowledge of CAN and practice of safeguarding. Child protection training is recommended. PMID- 29790775 TI - Dental, periodontal and salivary conditions in diabetic children associated with metabolic control variables and nutritional plan adherence. AB - AIM: Diabetes mellitus is a chronic disease that has manifestations other than alterations in endocrine regulation or in metabolic pathways. Several diseases of the oral cavity have been associated with diabetes mellitus type 1 and 2 in young people according to their evolution. Scarce information exists regarding the role of diabetes and its association with the oral health status in paediatric diabetic patients. The aims of the study were to assess the quality of saliva, saliva acidogenicity, dental caries experience, fluorosis and periodontal status in diabetic patients and to evaluate their relationship with metabolic control variables and nutritional plan adherence. MATERIALS AND METHODS: The study population consisted of 60 paediatric patients with both types of diabetes mellitus. Saliva testing included stimulated flow, pH (using pH indicator strips), buffer capacity and Snyder's Test. DMFT/dmft and dental caries experience were determined on the basis of ICDAS II codes. The periodontal status was assessed by PI and GI and fluorosis by FI. Nutritional plan adherence was established from the subscale "Dietary Control" of the Diabetes Self-Management Profile questionnaire. Medical Data was retrieved from the clinical registers in the Diabetic Clinic. RESULTS: We describe the main characteristics of the oral cavity related variables of our population that might guide the clinical practice in similar settings; we found a dmft/DMFT of 1.71 +/- 1.74 and 0.64 +/- 1.03, PI of 1.91 +/- 0.75, GI of 0.50 +/- 0.56 and a fluorosis prevalence of 61%. We identified several correlated variables, which indicate strong associations between the nutritional habits of the patients and co-occurrence of oral cavity physiopathological alterations. Several correlations were found between acidogenic activity of the saliva (Snyder Test) and the percentage of adherence to the nutritional plan and to the dmft index. Furthermore, a significant correlation between the buffering capacity of the saliva and the glycemic control of the participants was found. Neither an association nor a difference among means was found between treatment regime and the plaque index. CONCLUSION: The results of the present study concluded that there was a significant relationship between diabetes mellitus and an increased prevalence of oral cavity related diseases in the paediatric population. These are also associated with a poor adherence to the nutritional plan. PMID- 29790776 TI - Oral health challenges facing Dubai children with Autism Spectrum Disorder at home and in accessing oral health care. AB - AIM: To investigate the challenges faced by Autism Spectrum Disorder (ASD) children and their families in Dubai from three different perspectives of dental care: oral care at home, oral care at the dentist and access to oral care, and to compare the results to their normally developing peers. MATERIALS AND METHODS: A case-control comparative study of 84 ASD and 53 healthy children attending special needs centres and schools in Dubai including siblings of the autistic children. Data collection was by a survey questionnaire completed by parents or guardians. RESULTS: More parents of ASD children compared to parents of healthy children reported difficulties across almost all oral care variables explored. The majority of ASD children's parents (83.3%) reported that their children need assistance in brushing their teeth compared with 15.4% of the healthy controls (p value < 0.001). The ASD children's uncooperative behaviour increased during dental visits and significantly more parents (37%) rated their child's experience as negative compared with 9.5% among the parents of control children (p value=0.006). The autistic children had visited a dentist mostly for extractions. CONCLUSION: This study indicates that autistic children in Dubai experience more challenges and barriers to oral care than their typically developing healthy peers. PMID- 29790777 TI - Oral management of children with Henoch-Schonlein Purpura and associated Glomerulonephritis: a scoping review. AB - AIM: To perform a scoping review of the existing literature in order to gather the most relevant information in the paediatric dentistry field related to the oral management of children affected by Henoch-Schonlein Purpura and associated Glomerulonephritis (HSPG). MATERIALS AND METHODS: Using scoping review methodology for the screening and selection of valid articles, the steps of this review were the following: first, to pose a research question; second, to identify relevant studies; third, to select and retrieve the studies; fourth, to chart the critical data, and finally, to collate, summarise, and report the results from the included articles. Relevant articles published over a 25-year period, up to July 31, 2017, were identified and retrieved from four Internet databases: PubMed; EMBASE/Ovid; Ebsco/Dentistry & Oral Science Source, and the Cochrane Collaboration Library. RESULTS: By title and abstract screening and after removing duplicates, four articles were finally included in the scoping review. According to the extracted data, the following are the most important clinical issues to be considered: (1) the disease can appear as a consequence of a dental treatment, such as those indicated for oral infectious processes; (2) children with HSPG are highly susceptible to dental caries and apical periodontitis, and (3) in affected children, oral infectious foci must be exhaustively eradicated in order to avoid the dissemination of the infection. CONCLUSIONS: Paediatric Dentists should be aware of HSPG, because the disease can be triggered or worsen subsequent to dental treatment. Adequate treatment of oral active infectious processes, together with an exhaustive oral preventive programme and long-term patient screening, are the best management approaches for children with HSPG. PMID- 29790778 TI - Survey of family-related factors of children treated under dental general anaesthesia. AB - AIM: Treatment under general anaesthesia (DGA) is a rising trend in Finland. There is a great need to investigate the causes leading to it. Our purpose was to examine family-related factors reported by parents, such as the family size and favoring DGA in the family, and their influence on children being treated under DGA. This survey was based on a questionnaire targeted to parents of children whose dental treatment could not be performed in a conventional setting. MATERIALS AND METHODS: Guardians of 87 healthy children treated under DGA at a municipal health center in the city of Oulu, Finland, between November 2014 and December 2015 answered the questionnaire on family-related background factors and on the respondent's own as well as their child's presumed dental fear. RESULTS: According to most guardians (83.9% of the cases), the reason for DGA was caries. Male gender, vague family structure, large number of siblings (?4), and DGA history in the family were all important family-related background factors leading to DGA. Self-reported parental dental fear was quite common (25.3%). Children's dental fear reported by parents was associated with DGA in almost half of the cases (46.0%). CONCLUSIONS: The survey highlights the role of the entire family in association with children ending up being treated under DGA. It is essential for the success of dental health care to also consider family-related factors when planning the treatment, particularly with children demanding DGA. PMID- 29790779 TI - The Two by Four appliance: a nationwide cross-sectional survey. AB - AIM: The aim of the study was to investigate how widespread is the use of the 2 x 4 appliance among Italian general dentists and specialists in orthodontics, as well as the type of treatment employed and length of use. MATERIALS AND METHODS: We conducted a nationwide cross-sectional survey from July 14, 2016 to January 12, 2017 using an online questionnaire of 8 multiple choice questions, created by the SurveyMonkey(r) Company, on a population of Italian dentists and specialists in orthodontics affiliated with the Italian Society of Paediatric Dentistry (SIOI). This was made to assess how many clinicians knew and used this device in their clinical practice. We included 200 Italian dentists, 99 specialists in orthodontics and 101 general dentists of a mean age of 45 +/- 15 years. RESULTS: Results show that 93.94% of orthodontists have knowledge of and use this device in their clinical practice, while only 51.49% of the general dentists have knowledge of and use it (p<0.001). The 51.92% of dentists and the 52.13% of orthodontists used the 2x4 appliance to treat both space management and incorrect overjet. Most of general dentists and orthodontists combined the 2x4 appliance with pre-adjusted brackets and accessory components such as coil springs and power chains. While most of dentists (45.90%) used the 2x4 in association with appliances for space management, most of specialists (46.15%) applied the 2*4 in combination with both appliances for space management and high-pull headgear. Statistically significant differences were found also for the answers to the question "what is the average time of treatment?" among general dentists: the 32.79% used the 2 x 4 for less than 6 months of treatment, and the 67.21% used the 2 x 4 for more than 6 months of treatment. On the other hand 49.46% of orthodontists used the 2 x 4 for less than 6 months of treatment, and 50.54% of them for more than 6 months of treatment (p=0.041). CONCLUSIONS: We conclude that the 2 x 4 appliance is widespread among orthodontists and about half of the general dentists, 93.94% and 51.49% (p<0.001) respectively. We found that 67.21% of general dentists used the 2 x 4 for a more than 6 months of treatment. As far as the orthodontists, 49.46% used the device for less than 6 months of treatment and 50.54% of them for more than 6 months of treatment. These differences were statistically significant (p=0.041). PMID- 29790781 TI - Relationship between Severe Early Childhood Caries and dental development. AB - AIM: Severe early childhood caries (sECC) is a public health problem that continues to affect infants and preschool children worldwide. Knowledge of the changes in dental development is important for paediatric dentists in order to determine a treatment plan. The aim of this study was to investigate dental development in children with sECC, compared to age and gender-matched controls, by calculating the dental age (DA). MATERIALS AND METHODS: A total of 300 children (144 females, 156 males) with sECC aged 5 years were studied and compared with 300 control subjects (caries-free), case-matched for gender and age. The dental development was assessed using the DA estimation method of Demirjian et al. [1973], and data were statistically analysed using a 2-sided t test and chi-squared test. RESULTS: The mean differences between the DA and chronological age (CA) in the sECC females and males were 0.67+/-0.6 years and 0.98+/-0.6 years, respectively, whereas the results of the case controls were 1.44+/-0.8 years for the females and 1.57+/-0.6 years for the males. The differences between the sECC and case control groups were significant for both genders (p<0.001). CONCLUSION: Children with severe early childhood caries have lower rates of dental development when compared to normal children. PMID- 29790780 TI - Sagittal dentoskeletal modifications associated with different activation protocols of rapid maxillary expansion. AB - AIM: The aim of this study is to compare the sagittal dentoskeletal changes associated with different activation protocols of maxillary expander. MATERIALS AND METHODS: A total of 101 subjects with constricted maxillary arches (49 males and 52 females; mean age 10.08 +/- 1.57 years) were enrolled in the study. The study comprised also a control group of 20 subjects (11 females and 9 males, mean age 10.27 +/- 1.24 years) who were not treated during the observation period. All the subjects underwent rapid maxillary expansion with a stainless steel banded expander cemented to the maxillary first molars. The expansion screw was randomly activated with two different rapid maxillary expansion protocols (one-quarter per day or two-quarters per day). A statistical comparison between the sagittal cephalometric variations obtained in the two expansion groups was made, and compared with the untreated control group. Data were then stratified for skeletal maturation of each subject. RESULTS: The Wilcoxon rank-sum test shows statistically significant differences between the two RME activation protocols only for overjet. Statistically significant differences were reported in comparison with the control group. CONCLUSIONS: This study suggests that the increase in overjet after RME could be associated with faster activation protocols especially in subjects with lower skeletal maturation. PMID- 29790782 TI - Prevalence and progression of early childhood caries in Nis, Serbia. AB - AIM: Early childhood caries (ECC) entails the presence of one or more decayed, missing, or filled teeth in children aged up to 71 months. Our aim is to present the prevalence and progression of ECC in Nis, Serbia. MATERIALS AND METHODS: The study was performed at the Clinic of Dentistry in Nis;, involving 250 children aged 3 to 6 years. The prevalence of caries was presented using the dmf index. Depending on the progression, tooth decay was reported as dI (superficial decay), dII (deep decay), dp (pulpitis), dg (dental gangrene), and dx (chronic apical periodontitis). RESULTS: Our results show that in Nis; the dmf index was 2.38 in the studied children. Of all the decayed teeth, dI was found in 73.18%, and dII in 22.38% of the children. The complications of tooth decay (pulpitis, gangrene, periodontitis) were not highly prevalent: dp=1.41%; dg=1.01%; and dx=2.02%. CONCLUSION: Based on the obtained results, it can be concluded that the prevalence of early childhood caries is relatively high. Therefore, health education for parents has to be intensified, focusing on the significance of preservation of health of the primary teeth all the way to their physiological replacement with the permanent teeth. PMID- 29790783 TI - Dental Sealants. Part 2: Who should get dental sealants and when. AB - BACKGROUND: Despite the remarkable achievements in recent decades in oral prevention, sealants are still underused even if their efficacy is well documented and clinical practice guidelines are available in almost every developed country. The clinician should know who needs dental sealants and when, with particular focus on high risk patients and pre-school children. PMID- 29790784 TI - Neonatal Pulmonary Magnetic Resonance Imaging of Bronchopulmonary Dysplasia Predicts Short-Term Clinical Outcomes. AB - RATIONALE: Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current National Institute of Child Health and Human Development (NICHD)/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. OBJECTIVES: We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD-defined BPD disease severity and predict short-term respiratory outcomes. METHODS: A total of 42 neonates (20 severe BPD, 6 moderate, 7 mild, 9 non-BPD control subjects; 40 +/- 3-wk postmenstrual age) underwent quiet-breathing structural pulmonary MRI (ultrashort echo time and gradient echo) in a neonatal ICU-sited, neonatal-sized 1.5 T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared with clinical severity and short-term respiratory outcomes. Outcomes were predicted using univariate and multivariable models, including clinical data and scores. MEASUREMENTS AND MAIN RESULTS: MRI scores significantly correlated with severities and predicted respiratory support at neonatal ICU discharge (P < 0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support. CONCLUSIONS: Quiet-breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short-term outcomes more accurately than any individual standard clinical measure. Importantly, this nonionizing technique can be implemented to phenotype disease, and has potential to serially assess efficacy of individualized therapies. PMID- 29790785 TI - Mental health trajectories among women in Australia as they age. AB - OBJECTIVES: To ascertain the trajectories of mental health among women in Australia assessed in repeat waves from their early 70 s to the end of their lives or their mid 80 s. METHOD: Secondary analysis of data contributed by the 1921-26 cohort of the Australian Longitudinal Study of Women's Health Waves 1-6. Primary outcome was the 4-item SF-36 Vitality Subscale, which assesses mental health as life satisfaction, social participation, energy and enthusiasm. Structural, individual and intermediary factors were assessed using study specific and standardised measures. Trajectories were identified using Growth Mixture Modelling and associations with baseline characteristics with Structural Equation Modelling. RESULTS: 12,432 women completed Survey One. Three mental health trajectories: stable high (77%); stable low (18.2%) and declining from high to low (4.8%) were identified. Compared to the stable high group, women in the stable low group were significantly less physically active, had more nutritional risks, more recent adverse life events, fewer social interactions and less social support, reported more stress and were more likely to have a serious illness or disability at Survey One. The declining group had similar characteristics to the stable high group, but were significantly more likely to report at baseline that they had experienced recent financial, physical and emotional elder abuse. These interact, but not directly with socioeconomic position and marital status. CONCLUSION: Mental health among older women is related to social relationships, general health, access to physical activity and healthy nutrition, coincidental adverse life events and experiences of interpersonal violence, in particular elder abuse. PMID- 29790786 TI - The Impact of Disruption of the Care Delivery System by Commercial Laboratory Testing in a Children's Health Care System. AB - CONTEXT: - Disruption of outpatient laboratory services by routing the samples to commercial reference laboratories may seem like a cost-saving measure by the payers, but results in hidden costs in quality and resources to support this paradigm. OBJECTIVE: - To identify differences when outpatient tests are performed at a Children's Hospital lab compared to a commercial reference lab, and the financial costs to support the reference laboratory testing. DESIGN: - Outpatient testing was sent to 3 different laboratories, specified by the payer. Orders were placed in the Children's electronic health record, blood samples were drawn by the Children's phlebotomists, samples were sent to the testing laboratory, and results appeared in the electronic health record. Data comparing the time to result, cancelled samples, and cost to sustain the system of ordering and reporting were drawn from multiple sources, both electronic and manual. RESULTS: - The median time from phlebotomy to result was 0.7 hours for testing at the children's lab and 20.72 hours for the commercial lab. The median time from result posting to caregiver acknowledgment was 5.4 hours for the Children's lab and 18 hours for the commercial lab. The commercial lab cancelled 2.7% of the tests; the Children's lab cancelled 0.8%. The financial cost to support online ordering and resulting for testing performed at commercial labs was approximately $640,000 per year. CONCLUSIONS: - Both tangible monetary costs, plus intangible costs in delay in resulting, occur when the system of laboratory testing is disrupted. PMID- 29790787 TI - Colorectal Liver Metastases: A Pathologist's Guide to Creating an Informative Report and Improving Patient Care. AB - CONTEXT: - In this era of minimally invasive procedures for diagnosis, prognosis, and treatment, pathologists are at the forefront of analyzing specimens and are expected to make more specific diagnoses, providing additional information from the material they receive. OBJECTIVE: - To familiarize pathologists with the essential components of surgical pathology reports for colorectal liver metastases (CRLM) resections. DATA SOURCES: - Colorectal cancer is the third most common cancer in the world and the liver is the most frequent site of metastases. Not all patients are candidates for surgery initially and may be treated with neoadjuvant chemotherapy, most commonly with FOLFOX (5-fluorouracil/leucovorin and oxaliplatin) and FOLFIRI (5-fluorouracil/leucovorin and irinotecan), after which they may become surgical candidates. When CRLM resections are received post neoadjuvant, the pathologist needs to not only report margin status but also report details regarding the tumor's response to treatment, and should evaluate the nonneoplastic parenchyma for chemotherapy-related injury, such as sinusoidal obstruction syndrome and/or steatohepatitis that may be caused by treatment. If ancillary tests, such as molecular studies (eg, KRAS, BRAF, NRAS, and microsatellite instability), have been previously conducted, these results should be included in the report. If not, they should be ordered for the resection specimen. CONCLUSIONS: - In this review, we will describe strategies and practical approaches to maximize the information gained from CRLM resections. A checklist is provided that may be used while signing out these cases to remind pathologists of additional components they may wish to include in their reports to best guide patient management. PMID- 29790788 TI - No association of moon phase with stroke occurrence. AB - Stroke occurrence shows strong correlations with sleep disorders and even subtle sleep disturbances have been shown to affect ischemic stroke (IS) occurrence. Chronobiology also exerts effects, like the morning surge in IS occurrence. Lunar cycles have also been shown to affect sleep and other physiological processes, but studies on moon phases and its possible association with occurrence of stroke are rare and nonconclusive. Therefore, we studied the effects of moon phases on stroke hospitalizations and in-hospital mortality nationwide in Finland in 2004 2014. All patients aged >=18 years with IS or intracerebral hemorrhage (ICH) as primary discharge diagnosis were included. Daily number of admissions was treated as a response variable while moon phase, year and astronomical season were independent variables in Poisson regression modeling. We found no association between moon phases and stroke occurrence. The overall occurrence rates did not vary between different moon phases for IS or ICH (p = 0.61 or higher). There were no differences between moon phases in daily admission rates among men, women, young and old patients for any of the stroke subtypes. There was no difference in in-hospital mortality with regard to moon phase for IS or ICH overall (p = 0.19 or higher), nor in subgroup analyses. There were no significant interactions between moon phase and astronomical season for stroke occurrence or in-hospital mortality. To conclude, in this over a decade-long nationwide study including a total of 46 million person years of follow-up, we found no association between moon phases and occurrence or in-hospital mortality rates of IS or intracerebral hemorrhage. PMID- 29790789 TI - Assessment of the association between the frequency of micronucleus and p16INK4a/Ki-67 co-expression in patients with cervical intraepithelial lesions. AB - Human papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16INK4a and Ki-67 (p16INK4a/Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes. We analyzed the association between the frequency of MN in PBL and the amount of p16INK4a/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16INK4a/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16INK4a/Ki-67 co-expression restricted to the lower part of the epithelium and were considered low positive and the remaining 60% of cases were negative. The frequency of MN, NPBs and NBUDs differed significantly among groups. We found a statistically significant positive correlation between p16INK4a/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16INK4a/Ki-67 double immunostaining for histological samples with CIN 1. MN frequency in PBL might be useful for detecting genomic instability in cases of HPV infection and CIN. PMID- 29790790 TI - The effects of amantadine on traumatic brain injury outcome: a double-blind, randomized, controlled, clinical trial. AB - INTRODUCTION: Amantadine, as a dopamine receptor agonist, may stimulate and help the recovery of the nervous system after traumatic brain injury (TBI). METHODS: We performed this study as a double-blind, randomized, controlled clinical trial with target population including all patients with TBI who scored nine or lower on the Glasgow Coma Scale (GCS), admitted to our hospital between January 2013 and April 2014. The protocol included administration of the drug (placebo or amantadine) for 6 weeks and patient evaluation using the GCS and FOUR score on the first, third and seventh days after the drug was started. After 6 months from starting study drug, the patients were evaluated on the Mini-Mental State Examination, Glasgow Outcome Study, Disability Rating Scale and Karnofsky Performance Scale. RESULTS: We included 40 patients in the study. The mean age of the patients was 36.77 +/- 18.21. As an only important finding, the amantadine group registered an important rise between the first and the seventh day of study drug (?GCS7-GCS1) with p-value = 0.044. CONCLUSION: Based on our findings during the first week and the 6 months (since starting drug) follow-ups, prescribing amantadine did not lead to reportable effects on the patients' level of consciousness, memory, disability, cognition, mortality and performance. PMID- 29790791 TI - Age associated decrease of sialin in salivary glands. AB - Aging salivary glands are characterized by a reduced volume of acini, increased duct volume, decline in the rate of synthesis of proteins and their mRNA, and decreased saliva flow. Sialin is a versatile anion transporter that is highly expressed in salivary glands and may also participate in maintenance of salivary gland function. We investigated age-associated sialin expression in salivary glands. Submandibular glands of mice and human parotid gland were collected at different ages. Western blot and real-time reverse transcription-polymerase chain reaction were used to analyze the protein and mRNA expression levels of sialin, respectively. Immunohistochemical and immunofluorescence staining were used to evaluate the histological pattern of sialin expression. We found that the protein and mRNA expression levels of sialin decreased with aging. The expression of sialin in the striated and excretory ducts of both mouse and human glands were reduced with age. In the mouse glands, the basal 2/3 of the cytoplasm was stained, while in the human glands the stain extended to the luminal surface. Sialin was expressed in the basal cytoplasmic membrane of acini and in some myoepithelial-like cells in young salivary glands, but had nearly disappeared in the aged salivary glands. Changes in sialin expression may be associated with changes in physiological function of salivary glands with aging. PMID- 29790792 TI - Dorsal Plating for Intra-articular Middle Phalangeal Base Fractures With Volar Instability. AB - BACKGROUND: Intra-articular middle phalangeal base fractures with volar instability are rare injuries with scant literature on optimal management. Our purpose is to describe our method of dorsal plating and report postoperative outcomes. METHODS: This study is a retrospective case review of 5 patients with intra-articular middle phalangeal base fractures with volar proximal interphalangeal joint instability, measuring subjective, clinical, and radiographic outcomes. RESULTS: Patient age averaged 38.2 years (range, 23-56 years), and 80% were male. Sporting injuries were the most common mechanism (80%). Time to surgery averaged 7 days, and postoperative follow-up duration averaged 19.6 months (median 8 months). All fractures were intra-articular at the proximal interphalangeal joint with volar instability. There were no complications and no patients required secondary surgery. Grip strength was maintained and range of motion was good, based on the American Society for Surgery of the Hand Total Active Motion score. Average Quick Disability of the Arm, Shoulder and Hand was 0.5 (range, 0-2.3), 100% of patients were satisfied, and average visual analog pain score was 1.2. Patients returned to work at a median of 4 days. There was radiographic union at an average of 6.6 weeks (range, 6-7 weeks) in all fractures. CONCLUSIONS: Dorsal plating using a 1.5-mm modular hand plate is a viable option for rigid fixation of intra-articular middle phalangeal base fractures with volar instability. This fixation method allows for early range of motion without complications in this case series. All fractures united, and patients had minimal functional deficits and were able to maintain good range of motion. PMID- 29790793 TI - Increased arterial stiffness - similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well controlled hypertension. AB - PURPOSE: Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. MATERIALS AND METHODS: A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. RESULTS: Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. CONCLUSIONS: Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension. PMID- 29790794 TI - Association of morning blood pressure surge with carotid intima-media thickness and cardiac dysfunction in patients with cardiac syndrome-X. AB - : Background & hypothesis: We hypothesized that exaggerated morning blood pressure surge, may contribute in cardiac dysfunction and arterial stiffness in patients with cardiac syndrome X. Thus we investigated the impact of morning blood pressure surge on cardiac function and carotid intima-media thickness in subjects with cardiac syndrome X. METHODS: We studied patients with cardiac syndrome X using ambulatory blood pressure monitoring and investigated the association of morning blood pressure surge with carotid intima thickness, left atrial volume index and left ventricular filling (E/e'). Seventy patients with cardiac syndrome X were enrolled for the study and compared with 70 age and sex matched controls. RESULTS: Patients with cardiac syndrome X were stratified based on the systolic morning blood pressure surge value of control subjects to patients with exaggerated blood pressure surge (n = 42) and those with normal morning blood pressure surge (n = 28). Basal heart rate (p < .05), high sensitive C-reactive protein (p < .01), left atrial volume index (p < .01), E/e' (p < .01); carotid intima-media thickness (p < .001) and percentage of detected plaque (p < .005) were significantly higher in patients with exaggerated morning blood pressure surge group than those with morning blood pressure surge group. Morning blood pressure surge was significantly correlated with carotid intima-media thickness, high sensitive C-reactive protein, left atrial volume index and E/e' ratio in patients with cardiac syndrome X. In multivariate analysis, exaggerated morning blood pressure surge was the only independent predictor of increased carotid intima-media thickness (OR = 2.379; p < .001), and diastolic dysfunction (OR = 2.464; p < .001) in patients with cardiac syndrome X. CONCLUSION: Our data suggest that excessive morning blood pressure surge is an independent predictor for arterial stiffness and diastolic dysfunction in patients with cardiac syndrome X. PMID- 29790795 TI - Octa-arginine modified poly(amidoamine) dendrimers for improved delivery and cytotoxic effect of paclitaxel in cancer. AB - Cell penetrating peptides (CPP) have the ability to penetrate the cell membrane and have been associated with various cargos for their facile intracellular translocation. The current study involves the synthesis of a CPP, octa-arginine (R8)-modified poly(amidoamine) dendrimer of generation 4 (G4), which has additionally been PEGylated and conjugated to the poorly soluble anticancer drug, paclitaxel (PTX). The synthesized dendrimer conjugates were characterized by proton nuclear magnetic resonance (1H-NMR) Spectroscopy and zeta potential measurements and evaluated in vitro in cell monolayers and 3D spheroids. Cellular uptake study in human cervical cancer cell line (HeLa) revealed that R8 modification significantly improved the cell association of conjugates. G4-PTX- polyethylene glycol (PEG)-R8 conjugate demonstrated enhanced cytotoxic potential and higher induction of apoptosis compared to free PTX and G4-PTX-PEG. Further, the penetrability of fluorescently labeled F-G4-PTX-PEG-R8 was evaluated in 3D spheroids of HeLa at various depths by using confocal microscopy. G4-PTX-PEG-R8 induced cell death and inhibited the growth in 3D spheroids as competently as in monolayers. The enhanced intracellular translocation of R8-modified dendrimers resulted in improved anticancer efficacy of PTX. Therefore, the newly developed dendrimer system is efficient for the intracellular delivery of PTX in cancer cells and has a strong potential to be utilized as an effective chemotherapeutic agent for cancer. PMID- 29790796 TI - In vitro coagulation triggers anti-Aspergillus fumigatus neutrophil response. AB - AIM: To explore Aspergillus interactions with platelets in the blood, especially during clot formation. MATERIALS & METHODS: Aspergillus fumigatus resting or swollen conidia, germlings or hyphae were inoculated into blood sampled into tubes with or without anticoagulant. Interactions were explored using microscopy, and chemokine levels were determined. RESULTS: Anatomopathological examination of the clot revealed conidia and germlings colocalization with platelet aggregates, and neutrophil recruitment around aggregates. Transmission electron microscopy showed conidia and hyphae surrounded by neutrophils. Increased CCL5 and CXCL4 when conidia or germlings but not hyphae were added suggested they could be involved in neutrophil recruitment around aggregates. CONCLUSION: These data suggest platelets could trigger coagulopathy and activate neutrophils during aspergillosis. They open up new perspectives for aspergillosis management. PMID- 29790798 TI - Introductory paragraph. PMID- 29790797 TI - Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy. AB - HYPOTHESIS: The antitumor applications of curcumin (CUR) are limited because of its low water solubility, poor stability, and low bioavailability. We developed novel nanocarrier systems for tumour targeting and controlled CUR release and evaluated their therapeutic efficacy. EXPERIMENTS: The surface of mesoporous silica nanoparticles (MSN) was modified with hyaluronan (HA) or polyethyleneimine folic acid (PEI-FA) via disulfide bonds. The capacity of the resultant nanocarriers (MSN-HA and MSN-PEI-FA, respectively) for CUR delivery was evaluated in a breast cancer cell line and a mouse xenograft model. FINDINGS: MSN/CUR-PEI FA and MSN/CUR-HA were cytotoxic to MDA-MB-231 breast cancer cells. Both formulations showed an enhanced cellular uptake compared with that of a non targeted nanocarrier, with a greater cellular uptake of FA-modified nanoparticles than that of HA-modified nanoparticles. Accordingly, MSN-PEI-FA showed more precise targeting and higher accumulation in tumours than did MSN-HA, as visualized by live imaging. Both types of nanoparticles had good biocompatibility and low toxicity, and MSN/CUR-PEI-FA inhibited the tumour growth to a greater degree than did free CUR. Thus, MSN/CUR-PEI-FA are a promising drug delivery system for the treatment of breast cancer. PMID- 29790800 TI - Resolution of late-onset heart and liver failures after reversion of jejuno-ileal bypass: a case report. AB - OBJECTIVES: Jejuno-ileal bypass (JIB) was a kind of bariatric surgery performed from 1960s to 1980s, able to induce sustainable weight loss by creating a surgical short bowel syndrome. MATERIALS AND METHODS: We report a case of an octogenarian woman who underwent in the early eighties this kind of surgery with consequent 40 kg weight loss. After 27 years, she first developed a reversible metabolic cardiomyopathy that began with signs and symptoms of heart failure. Thereafter, she was diagnosed with severe intractable liver insufficiency. RESULTS: Despite her old age, the patient underwent reversal of JIB with consequent early improvement of hepatic function. CONCLUSIONS: This case demonstrate that in case of long-term and life-threatening complications, it is possible to successfully reverse JIB surgery after upto 30 years. The hypothesis on pathophysiology of heart and liver insufficiency are discussed. PMID- 29790802 TI - Anesthesia Technique Effects on Pain and Hospital Stay in Patients Undergoing Hemorrhoidectomy. PMID- 29790801 TI - Development and characterisation of polymeric microparticle of poly(d,l-lactic acid) loaded with holmium acetylacetonate. AB - Biodegradable polymers containing radioactive isotopes such as Holmium 166 (166Ho) have potential applications as beta particle emitters in tumour tissues. It is also a gamma ray emitter, allowing nuclear imaging of any tissue to be acquired. It is frequently used in the form of complexes such as holmium acetylacetonate (HoAcAc), which may cause damages in tissues next to the targets cancer cells, as it is difficult to control its linkage or healthy tissues radiotherapy effects. Poly(d,l-lactic acid), PDLLA, was used to encapsulate holmium acetylacetonate (HoAcAc) using an emulsion solvent extraction/evaporation technique. Microspheres with sizes between 20-53 um were extensively characterised. HoAcAc release from the microspheres was assessed through studies using Inductively Coupled Plasma - Optical Emission Spectroscopy, and the microspheres showed no holmium leakage after a period of 10 half-lives and following gamma irradiation. Thus, HoAcAc loaded microspheres are here presented as a potential system for brachytherapy and imaging purposes. PMID- 29790804 TI - The efficacy and safety of other cryotherapy compounds for the treatment of genital warts: a randomized controlled trial. AB - BACKGROUND: Cryotherapy using Wartner compound that contains a mixture of dimethyl ether (75%) and propane (25%) has been recently reported as an effective treatment for warts. The present study aimed to evaluate the safety and efficacy of Wartner in male patients with genital warts. METHODS: A Phase II parallel randomized clinical trial was performed on 16 Iranian men affected by genital warts who were referred to a dermatology clinic at Tehran University of Medical Sciences. Two genital warts of each patient were selected and randomly assigned to receive either Wartner (intervention) or liquid nitrogen (control). RESULTS: Two weeks after the treatment, the sizes of the lesions in control and intervention groups decreased by 17.87 +/- 2.14 mm2 and 15.81 +/- 1.80 mm2, respectively (p = .299). Fourteen days after a single session of treatment, 81% of lesions in the control group and 50% in the Wartner group were completely eradicated, however, the difference was not statistically significant (p = .063). CONCLUSIONS: The Wartner compound is as effective as the conventional cryotherapy method for treating genital warts. It is particularly valuable when there are contraindications or no access to common treatment options. PMID- 29790805 TI - Climbing the ladder from neuron to brain in Harold Atwood's laboratory. AB - Twenty years spent in one laboratory is sufficient to build a legacy of publications and a body of work to make an impact. However, the impact of our work was highest at the personal level, and time spent in Harold Atwood's laboratory was not a culmination of my career but rather a crucial path toward learning and maturing as a researcher. During that time, I experienced discoveries and lessons that shaped the next steps of my career. This article is written in gratitude for wonderful experiences and describes a few highlights that were especially memorable and influential. PMID- 29790803 TI - Ultrasound-guided delivery of thymidine kinase-nitroreductase dual therapeutic genes by PEGylated-PLGA/PIE nanoparticles for enhanced triple negative breast cancer therapy. AB - AIM: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. Since no targeted therapy is available, gene-directed enzyme prodrug therapy (GDEPT) could be an attractive strategy for treating TNBC. MATERIALS & METHODS: Polyethylene glycol (PEG)ylated-poly(lactic-co-glycolic acid)/polyethyleneimine nanoparticles (PLGA/PEI NPs) were synthesized and complexed with TK-NTR fusion gene. Ultrasound (US) and microbubble (MB) mediated sonoporation was used for efficient delivery of the TK-NTR-DNA-NP complex to TNBC tumor in vivo for cancer therapy. Therapeutic effect was evaluated by treating TNBC cells in vitro and tumor xenograft in vivo by using prodrugs ganciclovir (GCV) and CB1954. RESULTS: TNBC cells treated with GCV/CB1954 prodrugs after transfection of TK-NTR-DNA by PEGylated-PLGA/PEI NP resulted in high apoptotic-index. US-MB image-guided delivery of TK-NTR-DNA-NP complex displayed significant expression level of TK NTR protein and showed tumor reduction when treated with GCV/CB1954 prodrugs in TNBC xenograft in vivo. CONCLUSION: US-MB image-guided delivery of TK-NTR gene by PEGylated-PLGA/PEI NPs could be a potential prodrug therapy for TNBC in the clinic. PMID- 29790806 TI - Bisphenol S modulates concentrations of bisphenol A and oestradiol in female and male mice. AB - Concern over endocrine-disrupting actions of bisphenol A (BPA) has prompted some manufacturers to remove it from consumer products. Among the chemical replacements in "BPA-free" products are other bisphenol analogues, such as bisphenol S (BPS). Given evidence that BPA and BPS possess similar oestrogenic activity, their capacity to interact and disrupt oestrogen homeostasis should be examined. We investigated whether BPS can modulate concentrations of 14C-BPA, exogenous 3H-oestradiol (E2), or natural E2. CF-1 mice were each given a single subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BPS, then given a dietary supplement containing either 50 MUg/kg 14C-BPA or 5 MUCi (14.5 ng) 3H-E2. BPS treatment elevated 14C-BPA concentrations in blood serum and certain reproductive organs of both sexes, but reduced 3H-E2 concentrations in blood serum of females. In another experiment, natural E2 was measured in urine 2 12 h after injection of 0 (vehicle), 1, or 3 mg BPS. BPS reduced E2 concentrations at 10 h after injection in both sexes. These results are consistent with evidence that BPS and BPA compete for access to metabolic enzymes, and that BPS can disrupt oestrogen homeostasis. These findings demonstrate the importance of considering multiple toxicants when determining regulatory exposure limits. PMID- 29790807 TI - Study of mitochondrial DNA A1555G and C1494T mutations in a large cohort of women individuals. AB - Mammalian mitochondrial A1555G and C1494T mutations are the most common causes of aminoglycoside-induced and non-syndromic hearing loss. However, these two mutations always are studied in the subject of pedigrees analysis. In the present study, we aimed to investigate the genetic characteristic of the A1555G and C1494T mutations on the population-level sampling, and to study the A1555G pattern of maternal transmission in three heteroplasmic families. Four thousand two hundred and ten unrelated women with normal hearing were enrolled as subjects. We used a mutation detection kit to screen the prevalence of these two mutations and used denaturing high performance liquid chromatography (DHPLC) and DNA sequencing to detect three A1555G heteroplasmic pedigrees. The carrier rate of A1555G was 0.33%, and the carrier rate of C1494T was 0.02% in our cohort, but the rate of heteroplasmy in A1555G mutant carriers reached 21.4%. Mitochondrial A1555G mutation rate was significantly decreased during maternal transmission of the mutant. Strong purifying selection may determine the fate of mtDNA A1555G in the transmission of human population. PMID- 29790808 TI - Comparison of time to engraftment between autologous patients receiving washed versus non-washed cryopreserved peripheral blood stem cell products. AB - Washing cryopreserved peripheral blood stem cell (PBSC) products can decrease infusion-related adverse reactions but can also result in cell loss and reduced cell viability. To assess the risk and benefit of washing products, we compared the time to neutrophil and platelet engraftment between autologous patients that received washed products (n = 201) and non-washed products (n = 89). The effect of the other variables, including age, gender, diagnosis, transplant dose, method of stem cell mobilization, and growth factor support regimen post-transplant, was assessed. In multivariate analysis, direct thaw and infusion of non-washed products resulted in significantly faster neutrophil engraftment (p = .003) and platelet engraftment (p = .017) than washed products. The mean neutrophil and platelet engraftment times were 1.07 days faster and 2.27 days faster, respectively. In conclusion, direct thaw and infusion of cryopreserved PBSC without washing results in significantly shorter time to recovery of neutrophils and platelets after autologous transplantation. PMID- 29790809 TI - Characterization of in vitro and in vivo metabolism of leelamine using liquid chromatography-tandem mass spectrometry. AB - Leelamine is a diterpene compound found in the bark of pine trees and has garnered considerable interest owing to its potent anticancer properties. The aim of the present study was to investigate the metabolic profile of leelamine in human liver microsomes (HLMs) and mice using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that leelamine undergoes only Phase I metabolism, which generates one metabolite that is mono-hydroxylated at the C9 carbon of the octahydrophenanthrene ring (M1) both in vitro and in vivo. The structure and metabolic pathway of M1 were determined from the MSn fragmentation obtained by collision-induced dissociation using LC-MS/MS in HLMs. Cytochrome p450 (CYP) 2D6 was found to be the dominant CYP enzyme involved in the biotransformation of leelamine to its hydroxylated metabolite, whereas CYP2C19, CYP1A1, and CYP3A4 contributed to some extent. Moreover, we identified only one metabolite M1, in the urine, but none in the feces. In conclusion, leelamine was metabolized to a mono-hydroxyl metabolite by CYP2D6 and mainly excreted in the urine. PMID- 29790810 TI - A review of novel technologies and techniques associated with identification of bloodstream infection etiologies and rapid antimicrobial genotypic and quantitative phenotypic determination. AB - INTRODUCTION: The antimicrobial aspect of management of patients with blood stream infections (BSI) and sepsis is time critical. In an era of increasing antimicrobial resistance, rapid detection and identification of bacteria with antimicrobial susceptibility is crucial to direct therapy early in the course of illness. Molecular techniques offer a potential solution to this. Areas covered: In the present review the authors have discussed a number of novel solutions utilizing a variety of molecular techniques for pathogen detection, identification and antimicrobial susceptibility. The review is not designed to be an exhaustive literature review covering all diagnostic solutions ever developed, instead the authors have focused on what they have had experience using, evaluating or currently view as new and exciting with potential to revolutionize BSI diagnosis. The authors searched PubMed (Medline) and Google Scholar with terms: BSI, Bacteraemia, Candidaemia, Diagnostics, AST, Rapid, AMR, Novel and Blood Culture. The authors attended recent clinical microbiology technology congresses. Expert commentary: There are multiple exciting novel technologies at differing stages of development with potential to revolutionize diagnosis of BSI. More work is needed as well as a standardized assessment of different platforms in order to better understand the clinical and financial impacts these will have in clinical microbiology laboratories. PMID- 29790811 TI - Nanoscaffolds in promoting regeneration of the peripheral nervous system. AB - The ability to surgically repair peripheral nerve injuries is urgently needed. However, traditional tissue engineering techniques, such as autologous nerve transplantation, have some limitations. Therefore, tissue engineered autologous nerve grafts have become a suitable choice for nerve repair. Novel tissue engineering techniques derived from nanostructured conduits have been shown to be superior to other successful functional neurological structures with different scaffolds in terms of providing the required structures and properties. Additionally, different biomaterials and growth factors have been added to nerve scaffolds to produce unique biological effects that promote nerve regeneration and functional recovery. This review summarizes the application of different nanoscaffolds in peripheral nerve repair and further analyzes how the nanoscaffolds promote peripheral nerve regeneration. PMID- 29790812 TI - Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. AB - Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, an Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1.7 DIII-DIV linker (L3) as phosphorylation sites of Fyn. Whole cell recordings revealed that FynCA evoked larger changes in Nav1.7 biophysical properties when expressed in ND7/23 cells than in Human Embryonic Kidney (HEK) 293 cells, suggesting a cell type-specific modulation of Nav1.7 by Fyn kinase. In HEK 293 cells, substitution of both tyrosine residues with phenylalanine dramatically reduced current amplitude of mutant channels, which was partially rescued by expressing mutant channels in ND7/23 cells. Phenylalanine substitution showed little effect on FynCA-induced changes in Nav1.7 activation and inactivation, suggesting additional modifications in the channel or modulation by interaction with extrinsic factor(s). Our study demonstrates that Nav1.7 is a substrate for Fyn kinase, and the effect of the channel phosphorylation depends on the cell background. Fyn-mediated modulation of Nav1.7 may regulate DRG neuron excitability and contribute to pain perception. Whether this interaction could serve as a target for developing new pain therapeutics requires future study. PMID- 29790814 TI - A de novo mutation in PRICKLE1 associated with myoclonic epilepsy and autism spectrum disorder. AB - Homozygous recessive mutations in the PRICKLE1 gene were first described in three consanguineous families with myoclonic epilepsy. Subsequent studies have identified neurological abnormalities in humans and animal models with both heterozygous and homozygous mutations in PRICKLE1 orthologs. We describe a 7-year old with a novel de novo missense mutation in PRICKLE1 associated with epilepsy, autism spectrum disorder and global developmental delay. PMID- 29790815 TI - Maternal psychosocial stress and children's ADHD diagnosis: a prospective birth cohort study. AB - OBJECTIVE: Examine the association of mothers' psychosocial stressors before and during pregnancy with their children's diagnosis of attention deficit hyperactivity disorder (ADHD). METHODS: This study included 2140 mother-child pairs who had at least one postnatal pediatric visit at the Boston Medical Center between 2003 and 2015. Child ADHD was determined via International Classification of Diseases, Ninth Revision (ICD-9) codes documented in electronic medical records. Latent factors of maternal stress and social support and measures of the physical home environment and psychosocial adversities were constructed using exploratory factor analysis. The association between the latent factors and child ADHD diagnosis was examined using multiple logistic regression, controlling for known risk factors for ADHD. RESULTS: Children were 1.45 (95% CI: 1.06, 1.99) and 3.03 (95% CI: 2.19, 4.20) times more likely to receive an ADHD diagnosis if their mother experienced a major stressful event during pregnancy or reported a high level of perceived stress, respectively. The number of family adversities increases the risk of ADHD diagnosis [second quartile: OR = 1.90; CI (1.31, 2.77); third quartile: OR = 1.96 CI (1.34, 2.88); fourth quartile: OR = 2.89 CI (2.01, 4.16)] compared to first quartile. CONCLUSIONS: In this prospective, predominantly urban, low-income, minority birth cohort, mothers' psychosocial stress before and during pregnancy appears to be an independent risk factor for the development of ADHD in their children. PMID- 29790816 TI - The effect of elevated alpha1-acid glycoprotein on the pharmacokinetics of TAK 272 (SCO-272), an orally active renin inhibitor, in rats. AB - The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. Following intravenous administration of TAK-272 to the turpentine-treated rats, the systemic clearance and volume of distribution decreased with the elevated plasma alpha1-acid glycoprotein (AGP) levels. The elevated plasma AGP levels were negatively correlated with the plasma unbound fraction of TAK-272 in the rats. Although the AUCs of total TAK-272 in the turpentine-treated rats were higher than those in the control rats after intravenous and oral administration, those of unbound TAK-272, which seem to directly contribute to the pharmacological effect and safety, were nearly equal between the turpentine-treated and control rats in the respective dose routes. TAK-272 has been shown to primarily bind to AGP in the human plasma. These results strongly suggested that the pharmacokinetic of TAK-272 in humans would also be affected by the variation in the plasma AGP levels and should be discussed with not only the total concentrations but also the unbound concentrations in the clinical trial for patients with elevated plasma AGP levels. PMID- 29790817 TI - Letter Regarding the "Comparison of the Tight Rope Technique and Clavicular Hook Plate for the Treatment of Rockwood Type III acromioclavicular Joint Dislocation". PMID- 29790813 TI - Increased Nav1.7 expression in the dorsal root ganglion contributes to pain hypersensitivity after plantar incision in rats. AB - Postoperative pain remains a complex problem that is difficult to manage in the clinical context, seriously affecting rehabilitation and the quality of life of patients after surgery. Nociceptors, of which the cell bodies are located in the dorsal root ganglion, are crucial for initiating and conducting the pain signal. The peripheral voltage-gated sodium channels, including Nav1.7, which is mainly expressed in the dorsal root ganglion, are key to understanding the mechanism underlying postoperative pain. Nav1.7, in particular, of which mutations in the encoding gene ( SCN9A) can determine whether pain occurs, has aroused most attention. Previous studies have shown that Nav1.7 in dorsal root ganglion is critical for the development of inflammatory pain and some neuropathic pain. However, the expression of Nav1.7 in the dorsal root ganglion after surgery and its role in postoperative pain hypersensitivity remain unclear. Therefore, in this study, in order to gain a better understanding of the role of dorsal root ganglion Nav1.7 in pain hypersensitivity following operation, we dynamically examined the pain-related behavior and expression of Nav1.7 in L4-L6 dorsal root ganglion before and after plantar incision in rats (an acute postoperative pain model). After plantar incision, the mechanical and thermal pain threshold decreased significantly, the cumulative pain score was increased significantly, meanwhile quantitative polymerase chain reaction and Western blotting results showed that expression of Nav1.7 in L4-L6 dorsal root ganglion was enhanced significantly. After pretreatment using SCN9A-RNAi-LV delivered via an intrathecal tube, immunohistochemistry showed that increased expression of Nav1.7 in L4-L6 dorsal root ganglion after plantar incision was inhibited, as also confirmed by quantitative polymerase chain reaction and Western blotting. Moreover, pain hypersensitivity was alleviated. These results suggested that Nav1.7 of L4-L6 dorsal root ganglion plays an important role in the development of pain hypersensitivity after plantar incision. PMID- 29790818 TI - Endosomal and Phagosomal SNAREs. AB - The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking. Of the 38 SNAREs present in humans, 30 have been identified at endosomes and/or phagosomes. Many of these SNAREs are targeted by viruses and intracellular pathogens, which thereby reroute intracellular transport for gaining access to nutrients, preventing their degradation, and avoiding their detection by the immune system. A fascinating picture is emerging of a complex transport network with multiple SNAREs being involved in consecutive trafficking routes. PMID- 29790819 TI - Effects of astragaloside IV on the pharmacokinetics of puerarin in rats. AB - 1. Radix astragali and puerarin are always used together for cardiovascular disease in China clinics. 2. This study investigates the effects of astragaloside IV (AS-IV, the main components of radix astragali) on the pharmacokinetics of puerarin in rats. 3. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without AS-IV pretreatment (100 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using LC-MS/MS method, and the pharmacokinetics profiles were calculated and compared. Caco-2 cell transwell model was also used to investigate the effects of AS-IV on the transport pf puerarin. 4. The results showed that when the rats were pretreated with AS-IV, the maximum concentration (Cmax) of puerarin decreased from 760 to 467 ng/mL (P < 0.05, n = 6, 90%CI, 293 +/- 61.28), and the area under the concentration-time curve from zero to infinity (AUC0-inf) also decreased from 4097 to 2330 MUg.h/L (P < 0.05, n = 6). The oral clearance of puerarin increased significantly from 11.9 to 22.4 L/h/kg (P < 0.05, n = 6). The Caco-2 cell transwell experiments indicated that AS-IV could increase the efflux ratio of puerarin from 1.81 to 2.79 through inducing the activity of P-gp. 5. In conclusion, these results indicated that AS-IV could affect the pharmacokinetics of puerarin, possibly by decreasing the systemic exposure of puerarin by inducing the activity of P-gp. PMID- 29790820 TI - Towards quantitative [18F]FDG-PET/MRI of the brain: Automated MR-driven calculation of an image-derived input function for the non-invasive determination of cerebral glucose metabolic rates. AB - Absolute quantification of PET brain imaging requires the measurement of an arterial input function (AIF), typically obtained invasively via an arterial cannulation. We present an approach to automatically calculate an image-derived input function (IDIF) and cerebral metabolic rates of glucose (CMRGlc) from the [18F]FDG PET data using an integrated PET/MRI system. Ten healthy controls underwent test-retest dynamic [18F]FDG-PET/MRI examinations. The imaging protocol consisted of a 60-min PET list-mode acquisition together with a time-of-flight MR angiography scan for segmenting the carotid arteries and intermittent MR navigators to monitor subject movement. AIFs were collected as the reference standard. Attenuation correction was performed using a separate low-dose CT scan. Assessment of the percentage difference between area-under-the-curve of IDIF and AIF yielded values within +/-5%. Similar test-retest variability was seen between AIFs (9 +/- 8) % and the IDIFs (9 +/- 7) %. Absolute percentage difference between CMRGlc values obtained from AIF and IDIF across all examinations and selected brain regions was 3.2% (interquartile range: (2.4-4.3) %, maximum < 10%). High test-retest intravariability was observed between CMRGlc values obtained from AIF (14%) and IDIF (17%). The proposed approach provides an IDIF, which can be effectively used in lieu of AIF. PMID- 29790822 TI - The serotonin transporter polymorphism (5-HTTLPR) and cortisol stress responsiveness: preliminary evidence for a modulating role for sleep quality. AB - The short (S) allele of a functional polymorphism (5-HTTLPR) within the promoter region of the serotonin transporter gene (SLC6A4) is found to predispose the risk for stress-related affective disorders relative to the long (L) allele. Evidence suggests that elevated stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association although there is little understanding about the origin of inconsistent findings. Since inadequate sleep is commonly known to promote HPA stress reactivity, it might well play an important modulating role. The present study tested this hypothesis by investigating whether sleep quality moderates the relationship between 5-HTTLPR and cortisol stress responsiveness. From a large 5-HTTLPR database (n = 771), a sample of healthy male and female participants homozygous for either the 5-HTTLPR S-allele (n = 25) or L-allele (n = 25) were assessed for sleep quality and salivary cortisol secretion during acute laboratory stress. Diminished sleep quality was found to exclusively potentiate cortisol stress reactivity in the homozygous L allele genotype. Accounting for this 5-HTTLPR-dependent influence enhanced the predictive value of 5-HTTLPR on cortisol stress responsiveness, revealing greater HPA reactivity in S-allele relative to L-allele carriers. Current findings suggest that variations in sleep quality may serve as a confounding factor in the search for genetic differences in stress sensitivity and related affective disorders. PMID- 29790821 TI - Effects of immuno-related gene polymorphisms on a bispecific antibody targeting colorectal cancer cell. AB - BACKGROUND: Colorectal cancer (CRC) represents the third most common type of cancer and the third leading cause of death from cancer around the world. M701 is a CD3/EpCAM bispecific antibody that shows promising cytotoxicity toward CRC cells. AIM: To investigate the influence of immuno-related gene polymorphisms on M701 mediated cytotoxicity to CRC cell HCT116. METHOD: We analyzed the influence of the effect of M701 on the activation and cytotoxicity of peripheral mononuclear blood cells from 129 healthy volunteers with different genotypes. RESULT: When incubated with M701, peripheral mononuclear blood cells from CD247 rs2949655 AA homozygotes showed significantly lower cytotoxicity than those from AG/GG heterozygotes. CONCLUSION: CD247 rs2949655 was significantly associated with the cytotoxicity of M701 to HCT116, which might contribute to personalized medicine of M701. PMID- 29790823 TI - The world of the identified or digital neuron. AB - In general, neurons in insects and many other invertebrate groups are individually recognizable, enabling us to assign an index number to specific neurons in a manner which is rarely possible in a vertebrate brain. This endows many studies on insect nervous systems with the opportunity to document neurons with great precision, so that in favourable cases we can return to the same neuron or neuron type repeatedly so as to recognize many separate morphological classes. The visual system of the fly's compound eye particularly provides clear examples of the accuracy of neuron wiring, allowing numerical comparisons between representatives of the same cell type, and estimates of the accuracy of their wiring. PMID- 29790824 TI - Addressing the challenges of ECMO simulation. AB - INTRODUCTION/AIM: The patient's condition and high-risk nature of extracorporeal membrane oxygenation (ECMO) therapy force clinical services to ensure clinicians are properly trained and always ready to deal effectively with critical situations. Simulation-based education (SBE), from the simplest approaches to the most immersive modalities, helps promote optimum individual and team performance. The risks of SBE are negative learning, inauthenticity in learning and over reliance on the participants' suspension of disbelief. This is especially relevant to ECMO SBE as circuit/patient interactions are difficult to fully simulate without confusing circuit alterations. METHODS: Our efforts concentrate on making ECMO simulation easier and more realistic in order to reduce the current gap there is between SBE and real ECMO patient care. Issues to be overcome include controlling the circuit pressures, system failures, patient issues, blood colour and cost factors. Key to our developments are the hospital university collaboration and research funding. RESULTS: A prototype ECMO simulator has been developed that allows for realistic ECMO SBE. The system emulates the ECMO machine interface with remotely controllable pressure parameters, haemorrhaging, line chattering, air bubble noise and simulated blood colour change. CONCLUSION: The prototype simulator allows the simulation of common ECMO emergencies through innovative solutions that enhance the fidelity of ECMO SBE and reduce the requirement for suspension of disbelief from participants. Future developments will encompass the patient cannulation aspect. PMID- 29790825 TI - Epidemiological and clinical features of visceral leishmaniasis in children in Alicante Province, Spain. AB - BACKGROUND: Visceral leishmaniasis (VL) is endemic to the Mediterranean basin. In children, VL often presents with non-specific symptoms and can be life threatening without proper treatment. AIM: To describe the epidemiological and clinical features of pediatric VL in children in Alicante, Spain. METHODS: The study included all paediatric (<15 years) cases admitted to three hospitals in the province of Alicante from May 1992 to May 2015 with diagnosis of VL (detection was either by anti-Leishmania antibodies in serology or Leishmania in blood and/or bone marrow aspirates). RESULTS: There were 38 cases of pediatric VL (18 aged <24 months, 15 aged 24-59 months and 5 aged >=5 years). The main symptoms were fever (97.4%), followed by pallor (75.0%) and loss of appetite (46.4%). Eighty-seven per cent of patients were anaemic (haemoglobin < 9 g/dL), 73.7% had neutropenia and 68.4% had thrombocytopenia. Before 2004, 92.3% of patients were treated with meglumine antimoniate (MA) and 7.7% with liposomal amphotericin B (LAmB); after 2004, 84% were treated with LAmB and just one (16%) with MA (p < 0.001). LAmB performed better than MA in terms of mean treatment length (7.4 days vs 25.9 days, p < 0.001), time to becoming afebrile (1.7 vs 13.7 days, p < 0.001), and length of hospital stay (10.9 vs 19.4 days, p = 0.001). CONCLUSION: Paediatric VL in Alicante mainly affects children under five. Children aged <=24 months present with a lower haemoglobin and white blood cell count. Treatment with LAmB reduces treatment length, time to becoming afebrile and length of hospital stay. PMID- 29790826 TI - Free Clinics and the Need for Nursing Action in Uncertain Political Times. AB - Free clinics have been a source of health care for uninsured and low-income Americans for half a century and serve some of the nation's most vulnerable within their home community. Despite parallels to nursing's significant involvement in the formation of free public clinics and commitment to care for all, there is paucity of nursing literature about free clinics. This article details the history of U.S. free clinics and the intersections among free clinics and value-based care, health reform, and tax reform, including the Patient Protection and Affordable Care Act of 2010 and the Tax Cuts and Jobs Act of 2017. Challenges impacting free clinics are detailed, as well as strategies nurses may employ to support survival of free clinics and enhance service to their target populations. Roles for nurses in free clinic governance, management, and practice are described as well as suggestions for research, education, and public policy. PMID- 29790828 TI - The influence of pharmacogenomics on the protective effect of light-to-moderate alcohol use. PMID- 29790829 TI - Evaluating Implicit Emotions of Chinese University Students With Different Levels of Social Adjustment: Implicit Measurement Based on the Go/No-go Association Task. AB - In this study, 60 university students were selected as research participants based on the Chinese Student Adjustment Scale. Participants were divided into two groups: high level of social adjustment and low level of social adjustment. Then using the Go/No-go Association Task as the implicit association experimental paradigm, implicit emotions were evaluated by having participants respond to different facial expressions as quickly as possible. The group of participants with higher levels of social adjustment performed better when responding to self concepts with positive facial expressions, compared to responding to non-self concepts with either positive or negative facial expressions. Thus, they showed an implicit preference for processing information about self with positive emotions. The group of participants with lower levels of social adjustment did not show the same benefit when responding to self-concepts. Instead, they performed better when responding to other-related concepts with different facial expressions, irrespective of the emotional content. Thus, they manifested an implicit preference for processing information about others with different emotions, suggesting a deficiency in processing their own emotions. In addition, the results validated the objectivity of the Chinese Student Adjustment Scale as an assessment tool. PMID- 29790827 TI - The effect of maternal HIV status and treatment duration on body composition of HIV-exposed and HIV-unexposed preterm, very and extremely low-birthweight infants. AB - BACKGROUND: There is an evidence gap regarding the relationship between HIV exposure, body composition (and the quality thereof) and preterm infants. AIM: This study determined the body composition of HIV-exposed, preterm very low birthweight (VLBW) and extremely low-birthweight (ELBW) infants and to assess the effect of maternal HAART duration on the body composition of this vulnerable population. METHODS: A descriptive cross-sectional study was conducted. HIV exposed and -unexposed preterm infants (<37 weeks) with a birthweight of <=1200g were included. Maternal medical background was recorded. Infant body composition measurements were recorded weekly during the 28-day follow-up period. RESULTS: Thirty preterm infants (27%) were HIV-exposed. HIV-exposed infants had significantly (=0.01) lower gestational ages than HIV-unexposed infants (25-28 weeks). HIV-exposed infants had significantly lower measurements on day 21 and day 28 for triceps skinfold (TSF) (2.5 mm vs 2.7 mm, = 0.02 and 2.6 mm vs 2.9 mm, <0.01), subscapular skinfold (SSSF) (2.3 mm vs 2.6 mm, = 0.02 and 2.4 mm vs 2.7 mm, =<0.01) and fat mass percentage (FM%) (0.9% vs 1.4%, = 0.02 and 1.0% vs 1.5%, = 0.03). HIV-exposed infants whose mothers received HAART for >= 20 weeks were heavier and had a higher FM% and lower fat-free mass percentage (FFM%) at birth than HIV-exposed preterm infants whose mothers received highly active antiretroviral therapy for >= 4- < 20 weeks. CONCLUSION: Mothers receiving HAART could have increased risk of preterm delivery, and the duration of maternal HAART affects postnatal body composition of their infants. Body composition differs between HIV-exposed and HIV-unexposed preterm infants. PMID- 29790830 TI - Empyema necessitans in a six-month-old girl. AB - Empyema necessitans is a rare complication of acute bacterial pneumonia, especially in children. It is a complication of empyema characterised by the extension of pus from the pleural cavity into the thoracic wall to form a mass of purulent fluid in the adjacent soft tissue. An inflammatory chest wall mass following pneumonia caused by Streptococcus pneumonia in a six-month-old infant is reported. The case emphasises that children presenting with persistent fever and a painful chest wall mass following pneumonia should be investigated immediately as there might be an urgent need for surgery. PMID- 29790831 TI - Informal Recyclers' Health Inequities in Vancouver, BC. AB - We explore informal recyclers' perceptions and experiences of the social determinants of health in Vancouver, Canada, and investigate the factors that contribute to the environmental health inequities they experience. Based on in depth interviews with 40 informal recyclers and 7 key informants, we used a social determinants of health framework to detail the health threats that informal recyclers associated with their work and the factors that influenced their access to health-related resources and services. Our analysis reveals that the structural factors influencing environmental health inequities included insufficient government resources for low-income urbanites; the potential for stigma, clientization, and discrimination at some health and social service providers; and the legal marginalization of informal recycling and associated activities. We conclude that Vancouver's informal recyclers experience inequitable access to health-related resources and services, and they are knowledgeable observers of the factors that influence their own health and well being. PMID- 29790832 TI - Without Warning: Worker Deaths From Heat 2014-2016. AB - Worker deaths from heat exposure are unlike heat deaths in the general population; workers tend to be outside in variable temperatures and younger than sixty-five years. Climate change will increase the frequency, duration, and variability of hot temperatures. Public health warning systems, such as the Heat Index of the National Weather Service, do not generally account for workers' greater likelihood of exposure to direct sunlight or exertion. Only 28% of the 79 worker heat-related fatalities during 2014-2016 occurred on days when the National Weather Service warning would have included the possibility of fatal heat stroke. Common heat illness prevention advice ignores workers' lack of control over their ability to rest and seek cooler temperatures. Additionally, acclimatization, or phased-in work in the heat, may be less useful given temperature variability under climate change. Workers' vulnerability and context of heat exposure should inform public health surveillance and response to prevent heat illness and death. PMID- 29790833 TI - Alterations in the cortical control of standing posture during varying levels of postural threat and task difficulty. AB - Cortical excitability increases during the performance of more difficult postural tasks. However, it is possible that changes in postural threat associated with more difficult tasks may in themselves lead to alterations in the neural strategies underlying postural control. Therefore, the purpose of this study was to examine whether changes in postural threat are responsible for the alterations in corticospinal excitability and short-interval intracortical inhibition (SICI) that occur with increasing postural task difficulty. Fourteen adults completed three postural tasks (supported standing, free standing, or standing on an unstable board) at two surface heights (ground level or 3 m above ground). Single and paired-pulse magnetic stimuli were applied to the motor cortex to compare soleus (SOL) and tibialis anterior (TA) test motor-evoked potentials (MEPs) and SICI between conditions. SOL and TA test MEPs increased from 0.35 +/- 0.29 to 0.82 +/- 0.41 mV (SOL) and from 0.64 +/- 0.51 to 1.96 +/- 1.45 mV (TA), respectively, whereas SICI decreased from 52.4 +/- 17.2% to 39.6 +/- 15.4% (SOL) and from 71.3 +/- 17.7% to 50.3 +/- 19.9% (TA) with increasing task difficulty. In contrast to the effects of task difficulty, only SOL test MEPs were smaller when participants stood at high (0.49 +/- 0.29 mV) compared with low height (0.61 +/- 0.40 mV). Because the presence of postural threat did not lead to any additional changes in the excitability of the motor corticospinal pathway and intracortical inhibition with increasing task difficulty, it seems unlikely that alterations in perceived threat are primarily responsible for the neurophysiological changes that are observed with increasing postural task difficulty. NEW & NOTEWORTHY We examined how task difficulty and postural threat influence the cortical control of posture. Results indicated that the motor corticospinal pathway and intracortical inhibition were modulated more by task difficulty than postural threat. Furthermore, because the presence of postural threat during the performance of various postural tasks did not lead to summative changes in motor-evoked potentials, alterations in perceived threat are not responsible for the neurophysiological changes that occur with increasing postural task difficulty. PMID- 29790835 TI - Tuning for rate and duration of frequency-modulated sweeps in the mammalian inferior colliculus. AB - Responses of auditory duration-tuned neurons (DTNs) are selective for stimulus duration. We used single-unit extracellular recording to investigate how the inferior colliculus (IC) encodes frequency-modulated (FM) sweeps in the big brown bat. It was unclear whether the responses of so-called "FM DTNs" encode signal duration, like classic pure-tone DTNs, or the FM sweep rate. Most FM cells had spiking responses selective for downward FM sweeps. We presented cells with linear FM sweeps whose center frequency (CEF) was set to the best excitatory frequency and whose bandwidth (BW) maximized the spike count. With these baseline parameters, we stimulated cells with linear FM sweeps randomly varied in duration to measure the range of excitatory FM durations and/or sweep rates. To separate FM rate and FM duration tuning, we doubled (and halved) the BW of the baseline FM stimulus while keeping the CEF constant and then recollected each cell's FM duration tuning curve. If the cell was tuned to FM duration, then the best duration (or range of excitatory durations) should remain constant despite changes in signal BW; however, if the cell was tuned to the FM rate, then the best duration should covary with the same FM rate at each BW. A Bayesian model comparison revealed that the majority of neurons were tuned to the FM sweep rate, although a few cells showed tuning for FM duration. We conclude that the dominant parameter for temporal tuning of FM neurons in the IC is FM sweep rate and not FM duration. NEW & NOTEWORTHY Reports of inferior colliculus neurons with response selectivity to the duration of frequency-modulated (FM) stimuli exist, yet it remains unclear whether such cells are tuned to the FM duration or the FM sweep rate. To disambiguate these hypotheses, we presented neurons with variable duration FM signals that were systematically manipulated in bandwidth. A Bayesian model comparison revealed that most temporally selective midbrain cells were tuned to the FM sweep rate and not the FM duration. PMID- 29790834 TI - Interference between competing motor memories developed through learning with different limbs. AB - Learning from motor errors that occur across different limbs is essential for effective tool use, sports training, and rehabilitation. To probe the neural organization of error-driven learning across limbs, we asked whether learning opposing visuomotor mappings with the two arms would interfere. Young right handers first adapted to opposite visuomotor rotations A and B with different arms and were then reexposed to A 24 h later. We observed that relearning of A was never faster nor were initial errors smaller than prior A learning, which would be expected if there was no interference from B. Rather, errors were greater than or similar to, and learning rate was slower than or comparable to, previous A learning depending on the order in which the arms learned. This indicated robust interference between the motor memories of A and B when they were learned with different arms in close succession. We then proceeded to uncover that the order-dependent asymmetry in performance upon reexposure resulted from asymmetric transfer of learning from the left arm to the right but not vice versa and that the observed interference was retrograde in nature. Such retrograde interference likely occurs because the two arms require the same neural resources for learning, a suggestion consistent with that of our past work showing impaired learning following left inferior parietal damage regardless of the arm used. These results thus point to a common neural basis for formation of new motor memories with different limbs and hold significant implications for how newly formed motor memories interact. NEW & NOTEWORTHY In a series of experiments, we demonstrate robust retrograde interference between competing motor memories developed through error-based learning with different arms. These results provide evidence for shared neural resources for the acquisition of motor memories across different limbs and also suggest that practice with two effectors in close succession may not be a sound approach in either sports or rehabilitation. Such training may not allow newly acquired motor memories to be stabilized. PMID- 29790836 TI - Minocycline promotes posthemorrhagic neurogenesis via M2 microglia polarization via upregulation of the TrkB/BDNF pathway in rats. AB - Intracerebral hemorrhage (ICH) is a devastating disease worldwide with increasing mortality. The present study investigated whether minocycline was neuroprotective and induced M2 microglial polarization via upregulation of the TrkB/BDNF pathway after ICH. ICH was induced via injection of autologous blood into 150 Sprague Dawley rats. A selective TrkB antagonist [N2-2-2-oxoazepan-3-yl amino] carbonyl phenyl benzo (b) thiophene-2-carboxamide (ANA 12)] and agonist [ N-[2-(5-hydroxy 1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC)] were used to investigate the mechanism of minocycline-induced neuroprotection. Minocycline improved ICH-induced neurological deficits and reduced M1 microglia marker protein (CD68, CD16) expression as well as M2 microglial polarization (CD206 and arginase 1 protein). Minocycline administration enhanced microglia-neuron cross talk and promoted the proliferation of neuronal progenitor cells, such as DCX- and Tuj-1-positive cells, 24 h after ICH. Minocycline also increased M2 microglia derived brain-derived neurotrophic factors (BDNF) and the upstream TrkB pathway. ANA 12 reversed the neuroprotective effects of minocycline. HIOC exhibited the same effects as minocycline and accelerated neurogenesis after ICH. This study demonstrated for the first time that minocycline promoted M2 microglia polarization via upregulation of the TrkB/BDNF pathway and promoted neurogenesis after ICH. This study contributes to our understanding of the therapeutic potential of minocycline in ICH. NEW & NOTEWORTHY The present study gives several novel points: 1) Minocycline promotes neurogenesis after intracerebral hemorrhage in rats. 2) Minocycline induces activated M1 microglia into M2 neurotrophic phenotype. 3) M2 microglia secreting BDNF remodel the damaged neurocircuit. PMID- 29790837 TI - Modulation of spinal motor networks by astrocyte-derived adenosine is dependent on D1-like dopamine receptor signaling. AB - Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways. Here, we demonstrate that adenosine produced upon astrocytic stimulation modulates locomotor-related activity by counteracting the excitatory effects of D1LR signaling and does not act by previously described dopamine-independent pathways. In spinal cord preparations from postnatal mice, a D1LR agonist, SKF 38393, increased the frequency of locomotor-related bursting induced by 5 hydroxytryptamine and N-methyl-d-aspartate. Bath-applied adenosine reduced burst frequency only in the presence of SKF 38393, as did adenosine produced after activation of protease-activated receptor-1 to stimulate astrocytes. Furthermore, the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced burst frequency only in the presence of SKF 38393, indicating that endogenous adenosine produced by astrocytes during network activity also acts by modulating D1LR signaling. Finally, modulation of bursting by adenosine released upon stimulation of astrocytes was blocked by protein kinase inhibitor-(14-22) amide, a protein kinase A (PKA) inhibitor, consistent with A1R-mediated antagonism of the D1LR/adenylyl cyclase/PKA pathway. Together, these findings support a novel, astrocytic mechanism of metamodulation within the mammalian spinal cord, highlighting the complexity of the molecular interactions that specify motor output. NEW & NOTEWORTHY Astrocytes within the spinal cord produce adenosine during ongoing locomotor-related activity or when experimentally stimulated. Here, we show that adenosine derived from astrocytes acts at A1 receptors to inhibit a pathway by which D1-like receptors enhance the frequency of locomotor related bursting. These data support a novel form of metamodulation within the mammalian spinal cord, enhancing our understanding of neuron-astrocyte interactions and their importance in shaping network activity. PMID- 29790838 TI - Release of taurine and glutamate contributes to cell volume regulation in human retinal Muller cells: differences in modulation by calcium. AB - Neuronal activity in the retina generates osmotic gradients that lead to Muller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Muller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Muller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca2+ dependency in MIO-M1 cells. Swelling induced [3H]Tau/[3H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [3H]Tau and [3H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [3H]Tau efflux was mainly dependent on Ca2+ release from intracellular stores. RVD was unaffected in a Ca2+-free medium, probably due to Ca2+-independent Tau and Glu release, but was reduced by chelating intracellular Ca2+. The inhibition of phosphatidylinositol-3-kinase reduced [3H]Glu efflux but also the Ca2+-insensitive [3H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca2+-independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Muller cells. The observed disparities in Ca2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Muller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regulatory volume decrease response in a human Muller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca2+-dependent and -independent regulatory mechanisms, which strongly suggests that Muller cells may express different VRAC heteromers formed by the recently discovered leucine-rich repeat containing 8 (LRRC8) proteins. PMID- 29790839 TI - How to monitor breathing in laboratory rodents: a review of the current methods. AB - Accurately measuring respiration in laboratory rodents is essential for many fields of research, including olfactory neuroscience, social behavior, learning and memory, and respiratory physiology. However, choosing the right technique to monitor respiration can be tricky, given the many criteria to take into account: reliability, precision, and invasiveness, to name a few. This review aims to assist experimenters in choosing the technique that will best fit their needs, by surveying the available tools, discussing their strengths and weaknesses, and offering suggestions for future improvements. PMID- 29790840 TI - Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy. AB - Background Severe acute malnutrition (SAM) affects nearly 20 million children worldwide and is responsible for up to 1 million deaths per year in children under the age of 5 years. Current WHO guidelines recommend oral amoxicillin for children with uncomplicated malnutrition and parenteral benzylpenicillin and gentamicin for those with complicated malnutrition. Because of cost pressures and increasing antimicrobial resistance, the administration of empirical antibiotics for children with SAM has recently been debated. Methods A systematic review of the current published literature was undertaken to assess the efficacy, safety, cost-effectiveness and pharmacokinetics of antimicrobial treatment of children with SAM in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results The initial search found 712 papers, eight of which met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. International guidelines and clinical data registries were also reviewed which identified inconsistencies in current first- and second-line therapies and dosing regimens. Conclusion Current evidence supports the continued use of broad-spectrum oral amoxicillin for treating children with uncomplicated SAM as outpatients. There is no strong evidence to justify changing the current parenteral therapy guidelines for children admitted with complicated SAM, although they should be clarified to harmonise the dosage regimen of amoxicillin for the treatment of SAM to 40 mg/kg twice daily, and to continue parenteral antimicrobials beyond 2 days if indicated by the clinical condition. PMID- 29790841 TI - Guidelines for the management of paediatric cholera infection: a systematic review of the evidence. AB - Background Vibrio cholerae is a highly motile Gram-negative bacterium which is responsible for 3 million cases of diarrhoeal illness and up to 100,000 deaths per year, with an increasing burden documented over the past decade. Current WHO guidelines for the treatment of paediatric cholera infection (tetracycline 12.5 mg/kg four times daily for 3 days) are based on data which are over a decade old. In an era of increasing antimicrobial resistance, updated review of the appropriate empirical therapy for cholera infection in children (taking account of susceptibility patterns, cost and the risk of adverse events) is necessary. Methods A systematic review of the current published literature on the treatment of cholera infection in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was undertaken. International clinical guidelines and studies pertaining to adverse effects associated with treatments available for cholera infection were also reviewed. Results The initial search produced 256 results, of which eight studies met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. Conclusions In view of the changing non-susceptibility rates worldwide, empirical therapy for cholera infection in paediatric patients should be changed to single-dose azithromycin (20 mg/kg), a safe and effective medication with ease of administration. Erythromycin (12.5 mg/kg four times daily for 3 days) exhibits similar bacteriological and clinical success and should be listed as a second line therapy. Fluid resuscitation remains the cornerstone of management of paediatric cholera infection, and prevention of infection by promoting access to clean water and sanitation is paramount. PMID- 29790843 TI - Empirical antibiotic treatment for children suffering from dysentery, cholera, pneumonia, sepsis or severe acute malnutrition. PMID- 29790842 TI - Reviewing the WHO guidelines for antibiotic use for sepsis in neonates and children. AB - Background Guidelines from 2005 for treating suspected sepsis in low- and middle income countries (LMIC) recommended hospitalisation and prophylactic intramuscular (IM) or intravenous (IV) ampicillin and gentamicin. In 2015, recommendations when referral to hospital is not possible suggest the administration of IM gentamicin and oral amoxicillin. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for treating sepsis (taking into account susceptibility patterns, cost and risk of adverse events) in neonates and children is necessary. Methods Systematic literature review and international guidelines were used to identify published evidence regarding the treatment of (suspected) sepsis. Results Five adequately designed and powered studies comparing antibiotic treatments in a low-risk community in neonates and young infants in LMIC were identified. These addressed potential simplifications of the current WHO treatment of reference, for infants for whom admission to inpatient care was not possible. Research is lacking regarding the treatment of suspected sepsis in neonates and children with hospital-acquired sepsis, despite rising antimicrobial resistance rates worldwide. Conclusions Current WHO guidelines supporting the use of gentamicin and penicillin for hospital-based patients or gentamicin (IM) and amoxicillin (oral) when referral to a hospital is not possible are in accordance with currently available evidence and other international guidelines, and there is no strong evidence to change this. The benefit of a cephalosporin alone or in combination as a second-line therapy in regions with known high rates of non susceptibility is not well established. Further research into hospital-acquired sepsis in neonates and children is required. PMID- 29790844 TI - Antibiotic use for community-acquired pneumonia in neonates and children: WHO evidence review. AB - Background Pneumonia is the most common cause of death in children worldwide, accounting for 15% of all deaths of children under 5 years of age. This review summarises the evidence for the empirical antibiotic treatment of community acquired pneumonia in neonates and children and puts emphasis on publications since the release of the previous WHO Evidence Summary report published in 2014. Methods A systematic search for systematic reviews and meta-analyses of antibiotic therapy for community-acquired pneumonia was conducted between 1 January 2013 and 10 November 2016. Results The optimal dosing recommendation for amoxicillin remains unclear with limited pharmacological and clinical evidence. There is limited evidence from surveillance to indicate whether amoxicillin or broader spectrum antibiotics (e.g. third-generation cephalosporins) are being used most commonly for paediatric CAP in different WHO regions. Data are lacking on clinical efficacy in the context of pneumococcal, staphylococcal and mycoplasma disease and the relative contributions of varying first-line and step down options to the selection of such resistance. Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia. PMID- 29790847 TI - The development of a short version of TEMPS-A in Hungarian non-clinical samples. AB - BACKGROUND: The Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire (TEMPS-A) is a widely used measure of affective temperaments. Affective temperaments refer to people's prevailing moods and are important precursors of affective disorders. With the two studies presented in this paper, we aimed to develop a short version of the Hungarian TEMPS-A. METHODS: A total number of 1857 university students participated in two studies. The original 110 item version and the newly developed short version of TEMPS-A, the anger, depression, and anxiety scales of the PROMIS Emotional Distress item bank, the Altman Self-Rating Mania Scale, the Satisfaction With Life Scale, and the Well Being Index were administered to participants. RESULTS: Out of the original 110 items, 40 items of TEMPS-A loaded on five factors that represented the five affective temperaments. Factors of the short version showed moderate to strong correlations with their original counterparts. All factors had good to excellent internal reliability. Factors of the newly developed short version of TEMPSA showed meaningful correlations with measures of emotional distress, mania, and indices of psychological well-being. CONCLUSIONS: The short version of the Hungarian TEMPS-A is a promising instrument both in clinical fields and for academic research. The newly developed short version proved to be a valid and reliable measure of affective temperaments. PMID- 29790846 TI - Salipaludibacillus halalkaliphilus sp. nov., a moderately haloalkaliphilic bacterium from a coastal-marine wetland. AB - A Gram-stain-positive, endospore-forming rod-shaped non-motile, moderately halophilic and alkaliphilic bacterium, strain GASy1T, was isolated from a water sample from Gomishan, a marine wetland in Iran. GASy1T required at least 0.5 % (w/v) NaCl for growth and was able to grow at NaCl concentrations of up to 15 % (w/v), with optimum growth occurring at 5 % (w/v) NaCl. The optimum pH and temperature for growth were pH 8.5-9.0 and 30 degrees C, respectively, while it was able to grow over a pH range and a temperature range of 7.5-10.0 and 4-40 degrees C, respectively. GASy1T was catalase-positive and oxidase-negative. Analysis of 16S rRNA gene sequences revealed that GASy1T represents a member of the genus Salipaludibacillus, family Bacillaceae within the order Bacillales, showing 97.4 % sequence similarity to Salipaludibacillus neizhouensis JSM 071004T, and 96.2 and 95.7 % sequence similarity to Salipaludibacillus agaradhaerens AC 13T and Salipaludibacillus aurantiacus S9T, respectively. The DNA G+C content of GASy1T was 38.8 mol%. The polar lipids of the strain were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and two unidentified phospholipids and its major cellular fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C15 : 0. The isoprenoid quinone was MK-7. DNA-DNA hybridization experiments revealed a low level of relatedness between GASy1T and Salipaludibacillus neizhouensis IBRC-M 10892T (18 %). On the basis of a combination of phenotypic, chemotaxonomic and phylogenetic features, GASy1T represents a novel species of the genus Salipaludibacillus, for which the name Salipaludibacillus halalkaliphilus sp. nov. is proposed. The type strain of Salipaludibacillus halalkaliphilus is GASy1T (=IBRC M 10902T=LMG 28385T). PMID- 29790848 TI - [Assessing suicide risk using the Brief Suicide Questionnaire - preliminary results]. AB - The authors tested the clinical applicability of a self-developed, 6-item, clinician-rated questionnaire evaluating suicide risk in suicidal and non suicidal psychiatric inpatients and healthy controls. Results have shown that the questionnaires able to detect marked suicide risk in psychiatric inpatients with a high sensitivity and specificity which indicates its usefulness and good applicability in clinical practice. PMID- 29790849 TI - [N-methyl-D-aspartate receptor antibody encephalitis: the Janus-faced disorder]. AB - The recognition of the antibody-mediated encephalitis as a separate entity among the immune disorders of the central nervous system was one of the greatest breakthroughs of the last two decades in neurology. Unlike viral or tumor-related encephalitis, the antibody-mediated form has a good response to immunotherapy, which gives a special clinical importance to the discovery. Anti-N-methyl-D aspartate receptor (anti-NMDAR) encephalitis is one of the first fully characterized antibody-mediated encephalitises. This article attempts to summarize the clinical features of this complex neuropsychiatric disorder with the aim to help its early recognition and to report the clinical course and the outcome of our six seropositive anti-NMDAR cases. The disease appears typically in young females and often combined with ovarian teratoma. However, the antibody production could develop without any malignancy. The course of the illness is usually monophasic, but 10% of the cases are relapsing. The anti-NMDAR encephalitis is the result of disturbed glutamatergic neurotransmission due to the internalization of the receptor-antibody complexes. The disease usually develops after a common viral infection, but recent data proved that anti-NMDAR encephalitis could also develop after herpes simplex virus-1 encephalitis. The Janus-faced clinical course of the disease is the obstacle of the early recognition. Psychiatric symptoms - like delusion, hallucination and agitation - dominate in the first, cortical phase of the illness, which are indistinguishable from the signs of primary psychosis. The true nature of the disease only reveals later, with the appearance of the basal ganglia territory and brainstem sings, such as perioral hyperkinesia and bradycardia. Further delays the diagnosis that the leading symptoms of the second phase could be interpreted as the side effects of the initial treatment. According to expert psychiatrists, the unusual dynamic of the psychotic symptoms and the lack of response to the neuroleptic drugs could lead toward the idea of the anti-NMDAR encephalitis. The final diagnosis depends on the detection of the anti-NMDAR antibody from the cerebrospinal fluid or the serum, respectively. Haloperidol is the most potent drug to treat the psychotic symptoms of the cortical phase; however due to its antidopaminergic side effect atypical neuroleptics are recommended by the experts. The immunological treatment is the administration of intravenous corticosteroid combined with plasma exchange or with intravenous IgG infusion. The immunotherapy in most of the cases is successful, but the recovery is long and it requires strong cooperation between the psychiatrists, neurologists and intensive care therapists. PMID- 29790845 TI - Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence. AB - BACKGROUND: Shigella remains the primary cause of diarrhoea in paediatric patients worldwide and accounts for up to 40,000 deaths per year. Current guidelines for the treatment of shigellosis are based on data which are over a decade old. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for shigellosis in children is necessary, taking into account susceptibility patterns, cost and the risk of adverse events. METHODS: A systematic review of the current published literature on the treatment of shigella dysentery was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: The initial search produced 131 results, of which nine studies met the inclusion criteria. The quality of the studies was assessed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. International guidelines were also reviewed. There is a lack of current research regarding the clinical treatment of shigellosis in paediatric and adult patients, despite rising antimicrobial resistance worldwide. In particular, there is a lack of studies assessing the non-susceptibility of community-acquired strains, with almost all published research pertaining to microbiological data from hospital based settings. DISCUSSION: Current WHO guidelines support the use of fluoroquinolones (first-line), beta-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against the risk of dissemination of extended-spectrum beta lactamase-producing organisms. PMID- 29790850 TI - [The practical considerations of antidepressant use during pregnancy and breastfeeding]. AB - Main indications of antidepressants (ADs) as major depressive disorder (MDD) and different kinds of anxiety disorders are quite prevalent during pregnancy and the postpartum period. Due to the possible hazards of in utero and breast milk exposition of ADs, both psychiatrists and mothers frequently have concerns about the use of ADs during the periods of pregnancy and breastfeeding. However, we should also bear in mind that affective disorders left untreated during these periods are also associated with health risks for the mother and the baby as well. Accordingly, the treatment of affective disorders during these periods is essential. For mild cases of affective disorders the recommended treatment modality is typically psychotherapy while for the severe cases pharmacotherapy (including AD treatment) is recommended. Unfortunately, due to the lack of well designed prospective studies, only sparse information is available on the efficacy and safety of AD treatment in pregnant and breastfeeding women. In this review we try to provide some practical advice in terms of the use of ADs during the periods in question. PMID- 29790851 TI - RIG-I enhances interferon-alpha response by promoting antiviral protein expression in patients with chronic hepatitis B. AB - BACKGROUND: Interferon (IFN)-alpha is widely used for the treatment of chronic hepatitis B (CHB) infection due to the high rate of hepatitis B surface antigen (HBsAg) seroconversion. However, IFN-alpha treatment has a number of side effects. Thus, identification of molecular biomarkers to predict IFN-alpha therapeutic effect would be useful in the clinic. In this study, we aimed to investigate the role of retinoic acid-inducible gene-I (RIG-I) in prediction of IFN-alpha curative effect of CHB patients. METHODS: A total of 65 CHB patients treated with pegylated IFN-alpha weekly for 48 weeks were enrolled. Real-time PCR was performed for detection of RIG-I and IFN-stimulated gene (ISG) expression. In vitro, the HepG2 cells were transfected with siRNA and levels of RIG-I and anti HBV proteins were detected by western blot. The P-values were calculated in SPSS 18.0. The statistical significance level was accepted as P<0.05. RESULTS: In this study, we found RIG-I expression in peripheral blood mononuclear cells was higher in responder than non-responder CHB patients treated with IFN-alpha therapy. In HBV-transfected HepG2 and Huh7 cells, RIG-I enhanced IFN-alpha response by promoting anti-HBV protein expression such as double-stranded RNA-dependent protein kinase (PKR), oligoadenylate synthetase (OAS), adenosine deaminase (ADAR1) and Mx protein. Knocking down of RIG-I could downregulate the expression of these proteins. Inhibited RIG-I expression by RIG-I siRNA deceased STAT1 phosphorylation. CONCLUSIONS: Our results revealed RIG-I enhanced IFN-alpha response by promoting antiviral protein expression via the STAT1 pathway. RIG-I may be a new predictive factor for prediction of IFN-alpha efficacy in CHB patients. PMID- 29790852 TI - The lower symmetry electron-density distribution and the charge transport anisotropy in cubic dodecaboride LuB12. AB - High-quality single crystals of LuB12 are grown using the induction zone melting method. The x-ray data are collected at temperatures 293, 135, 95, 50 K. The crystal structure of LuB12 can be refined with record low R-factor in the cubic Fm [Formula: see text] m symmetry group despite reiterated observations of the cubic symmetry distortions both in the unit-cell values and in the physical properties. A peculiar computing strategy is developed to resolve this contradiction. True symmetry of the electron-density distribution in LuB12 is proved to be much lower than cubic as a result, which correlates very accurately with anisotropy of transport properties of LuB12. PMID- 29790853 TI - Wide-band 'black silicon' with atomic layer deposited NbN. AB - Antireflection surfaces are often utilized in optical components to reduce undesired reflection and increase absorption. We report on black silicon (b-Si) with dramatically enhanced absorption over a broad wavelength range (250-2500 nm) achieved by applying a 10-15 nm conformal coating of NbN with atomic layer deposition (ALD). The improvement is especially pronounced in the near infrared (NIR) range of 1100-2500 nm where absorption is increased by >90%. A significant increase of absorption is also observed over the ultraviolet range of 200-400 nm. Preceding NbN deposition with a nanostructured ALD Al2O3 (n-Al2O3) coating to enhance the NbN texture was also examined. Such texturing further improves absorption in the NIR, especially at longer wavelengths, strong absorption up to 4-5 MUm wavelengths has been attested. For comparison, double side polished silicon and sapphire coated with 10 nm thick NbN exhibited absorption of only ~55% in the NIR range of 1100-2500 nm. The results suggest a positive correlation between the surface area of NbN coating and optical absorption. Based on the wide band absorption, the presented NbN-coated b-Si may be an attractive candidate for use in e.g. spectroscopic systems, infrared microbolometers. PMID- 29790854 TI - Superior ionic and electronic properties of ReN2 monolayers for Na-ion battery electrodes. AB - Excellent monolayer electrode materials can be used to design high-performance alkali-metal-ion batteries. Here, we propose two-dimensional ReN2 monolayers as superior sodium-ion battery materials. Our total energy optimization results in a buckled tetragonal structure for the ReN2 monolayer, and our phonon spectrum and elastic moduli prove that it is dynamically and mechanically stable. Further investigations show that it is metallic and still keeps its metallic feature after the adsorption of Na or K atoms, and the adsorption of Na (or K) atoms changes the lattice parameters by 3.2% (or 3.8%) at most. Its maximum capacity reaches 751 mA h g-1 for Na-ion batteries or 250 mA h g-1 for K-ion batteries, and the diffusion barrier is only 0.027 eV for the Na atom or 0.127 eV for the K atom. The small lattice changes, high storage capacity, metallic feature, and extremely low ion diffusion barriers make the ReN2 monolayers a superior electrode material for Na-ion rechargeable batteries with ultrafast charging/discharging processes. PMID- 29790855 TI - Rhombohedral R3c to orthorhombic Pnma phase transition induced by Y-doping in BiFeO3. AB - In this work we study, by means of ab initio calculations, the structural, electronic and magnetic properties of Y-doped BiFeO3 compounds. We determine that there is a morphotropic phase boundary at an yttrium concentration of [Formula: see text], where the structure changes from R3c to Pnma. This structural transition is driven by the chemical pressure induced by the dopant. By analyzing the evolution of the oxygen octahedral tilts we find an enhanced antiferrodistortive distortion when increasing the Y-doping, together with a reduction of the ferroelectric distorsion, that gives rise to a smaller value of the electric polarization. These cooperative effects should lead to a larger canting of the Fe magnetic moments and to a larger ferromagnetic response in the R3c phase, as it is observed in the experiments. PMID- 29790856 TI - Surface terminations of hematite (alpha-Fe2O3) exposed to oxygen, hydrogen, or water: dependence on the density functional theory methodology. AB - Hematite (alpha-Fe2O3) is the most stable and abundant iron oxide in nature, and is used in many important environmental and industrial technologies, such as waste-water treatment, gas sensors, and photoelectrocatalysis. A clear understanding of the structure, composition, and chemistry of the hematite surface is crucial for improving its function in these technologies. Here we employ density functional theory (DFT) together with the DFT+U approach using semi-local functionals, as well as hybrid functionals, to study the structure, stability, and electronic properties of the (0 0 0 1) surface exposed to oxygen, hydrogen, or water. The use of hybrid functionals allow for a description of strong correlation without the need for atom-specific empirical parameters (i.e. U). However, we find that PBE+U, and in part also PBE, give similar results as the hybrid functional HSE(12%) in terms of structure optimization. When it comes to stability, work function, as well as electronic structure, the results are sensitive to the choice of functionals, but we cannot judge which level of functional is most appropriate due to the lack of experimental observations. PMID- 29790858 TI - Focused electron-beam-induced deposition for fabrication of highly durable and sensitive metallic AFM-IR probes. AB - We report on the fabrication of metallic, ultra-sharp atomic force microscope tips for localized nanoscale infrared (IR) spectrum measurements by using focused electron-beam-induced deposition of platinum or tungsten. The tip length can be controlled by changing the duration time of the electron beam. Probes of 12.0 +/- 5.0 nm radius-of-curvature can be routinely produced with high repeatability and near-100% yield. The near-field-enhancement appears stronger at the extremity of the metallic tip, compared with commercial pristine silicon-nitride probe tip. Finally, the performance of the modified metallic tips is demonstrated by imaging PVDF and PMMA thin films, which shows that spatial resolution is greatly enhanced. In addition, the signal intensity of the localized nanoscale IR spectrum is increased offering greater sensitivity for chemical IR imaging. PMID- 29790859 TI - Neutron track length estimator for GATE Monte Carlo dose calculation in radiotherapy. AB - The out-of-field dose in radiation therapy is a growing concern in regards to the late side-effects and secondary cancer induction. In high-energy x-ray therapy, the secondary neutrons generated through photonuclear reactions in the accelerator are part of this secondary dose. The neutron dose is currently not estimated by the treatment planning system while it appears to be preponderant for distances greater than 50 cm from the isocenter. Monte Carlo simulation has become the gold standard for accurately calculating the neutron dose under specific treatment conditions but the method is also known for having a slow statistical convergence, which makes it difficult to be used on a clinical basis. The neutron track length estimator, a neutron variance reduction technique inspired by the track length estimator method has thus been developped for the first time in the Monte Carlo code GATE to allow a fast computation of the neutron dose in radiotherapy. The details of its implementation, as well as the comparison of its performances against the analog MC method, are presented here. A gain of time from 15 to 400 can be obtained by our method, with a mean difference in the dose calculation of about 1% in comparison with the analog MC method. PMID- 29790860 TI - Long-lived photoluminescence polarization of localized excitons in liquid exfoliated monolayer enriched WS2. AB - Monolayer transition metal dichalcogenides (TMDs) constitute a family of materials, in which coupled spin-valley physics can be explored and which could find applications in novel optoelectronic devices. However, before applications can be designed, a scalable method of monolayer extraction is required. Liquid phase exfoliation is a technique providing large quantities of the monolayer material, but the spin-valley properties of thus obtained TMDs are unknown. In this work, we employ steady-state and time-resolved photoluminescence (PL) to investigate the relaxation dynamics of localized excitons (LXs) in liquid exfoliated WS2. The results reveal that the circular polarization lifetime of the PL exceeds by at least an order of magnitude the PL lifetime. A rate equations model allows us to reproduce quantitatively the experimental data and to conclude that the observed large and long-lived PL polarization originates from efficient trapping of free excitons at localization sites hindering the intervalley relaxation. Furthermore, our results show that the depolarization process is inefficient for LXs. We discuss various mechanisms leading to this effect such as suppression of intervalley scattering of the LXs or inefficient spin relaxation of the holes. PMID- 29790857 TI - Attenuation correction for brain PET imaging using deep neural network based on Dixon and ZTE MR images. AB - Positron emission tomography (PET) is a functional imaging modality widely used in neuroscience studies. To obtain meaningful quantitative results from PET images, attenuation correction is necessary during image reconstruction. For PET/MR hybrid systems, PET attenuation is challenging as magnetic resonance (MR) images do not reflect attenuation coefficients directly. To address this issue, we present deep neural network methods to derive the continuous attenuation coefficients for brain PET imaging from MR images. With only Dixon MR images as the network input, the existing U-net structure was adopted and analysis using forty patient data sets shows it is superior to other Dixon-based methods. When both Dixon and zero echo time (ZTE) images are available, we have proposed a modified U-net structure, named GroupU-net, to efficiently make use of both Dixon and ZTE information through group convolution modules when the network goes deeper. Quantitative analysis based on fourteen real patient data sets demonstrates that both network approaches can perform better than the standard methods, and the proposed network structure can further reduce the PET quantification error compared to the U-net structure. PMID- 29790861 TI - Assessing MR-linac radiotherapy robustness for anatomical changes in head and neck cancer. AB - The MR-Linac will provide excellent soft tissue contrast for on-treatment imaging. It is well known that the electron return effect (ERE) results in areas of increased and decreased dose at air/tissue boundaries, which can be compensated for in plan optimisation. However, anatomical changes may affect the quality of this compensation. In this paper we aim to quantify the interaction of anatomical changes with ERE in head and neck (H&N) cancer patients. Twenty patients treated with either 66 Gy or 60 Gy in 30 fractions were selected. Ten had significant weight-loss during treatment requiring repeat CT (rCT) and ten had PTVs close to the sinus cavity. Plans were optimised using Monaco to meet the departmental dose constraints and copied to the rCT and re-calculated. For the sinus patients, we optimised plans with full and empty sinus at both 0 T and 1.5 T. The effect of the opposite filling state was next evaluated. No clinically relevant difference between the doses in the PTV and OARs were observed related to weight-loss in 0 T or 1.5 T fields. Variable sinus filling caused greater dosimetric differences near the walls of the sinus for plans optimised with a full cavity in 1.5 T, indicating that optimising with an empty sinus makes the plan more robust to changes in filling. These findings indicate that current off line strategies for adaptive planning for H&N patients are also valid on an MR linac, if care is taken with sinus filling. PMID- 29790862 TI - A type-I van der Waals heterobilayer of WSe2/MoTe2. AB - We present a joint theoretical/experimental study of a van der Waals heterobilayer with type-I band alignment formed by monolayers of WSe2 and MoTe2. Our first-principles computation suggests that both the valence band maximum and the conduction band minimum of the WSe2/MoTe2 heterobilayer reside in the MoTe2 layer. The type-I band alignment allows efficient transfer of excitons from WSe2 to MoTe2. Since monolayer MoTe2 is a direct semiconductor with a bandgap in the infrared range, this heterobilayer is attractive for infrared light emission applications. Time-resolved measurements of photocarrier dynamics were conducted to provide experimental evidence of the type-I nature of this heterobilayer. In these measurements, we found that excitation energy can transfer from WSe2 to MoTe2 efficiently, but not along the opposite direction. The efficient energy transfer can serve as an optical gain or wavelength conversion mechanism for efficient emission from MoTe2, which can be utilized in ultrathin and efficient infrared light sources. PMID- 29790863 TI - Fabrication of ion bombardment induced rippled TiO2 surfaces to influence subsequent organic thin film growth. AB - Control over organic thin film growth is a central issue in the development of organic electronics. The anisotropy and extended size of the molecular building blocks introduce a high degree of complexity within the formation of thin films. This complexity can be even increased for substrates with induced, sophisticated morphology and anisotropy. Thus, targeted structuring like ion beam mediated modification of substrates in order to create ripples, pyramids, or pit structures provides a further degree of freedom in manipulating the growth morphology of organic thin films. We provide a comprehensive review of recent work on para-hexaphenyl (C36H26, 6P) as a typical representative of the class of small, rod-like conjugated molecules and rutile TiO2(1 1 0) as an example for a transparent oxide electrode to demonstrate the effect of ion beam induced nanostructuring on organic thin film growth. Starting from molecular growth on smooth, atomically flat TiO2(1 1 0) (1 * 1) surfaces, we investigate the influence of the ripple size on the resulting 6P thin films. The achieved 6P morphologies are either crystalline nano-needles composed of flat lying molecules or islands consisting of upright standing 6P, which are elongated in ripple direction. The islands' length-to-width ratio can be controlled by tuning the ripples' shape. PMID- 29790864 TI - Implementing Comprehensive Primary Care Referral Tracking in a Patient-Centered Medical Home. AB - The Patient-Centered Medical Home care model emphasizes efficient, coordinated care distributed among interdisciplinary team members. One key function to care coordination is referral/test tracking. This study evaluated the referral practices in a nurse-managed Patient-Centered Medical Home primary care clinic. The major findings corroborate the need for a well-organized referral-tracking system that is centralized and contains safety nets to reduce the number of delayed or missed referrals. PMID- 29790865 TI - Effect of Joint Camp on Patient Outcomes Following Total Joint Replacement. AB - Two major cost concerns related to joint replacement surgery are patient length of stay (LOS) and 30-day hospital readmission rates. A quality improvement project was implemented to evaluate the impact of a joint replacement program on patient readmissions and hospital LOS. A total of 1425 patients older than 50 years participated. At the end of the project period, readmission rates decreased from 6.19% to 2.8% and average LOS decreased from 5.87 days to 2.7 days. PMID- 29790866 TI - Audit and Feedback: A Quality Improvement Study to Increase Pneumococcal Vaccination Rates. AB - The purpose of this quality improvement study was to explore the impact of audit and feedback on the pneumococcal immunization rate for at-risk adults in ambulatory settings. Study findings support the hypothesis that timely, individualized audit and feedback can have a positive impact on immunization rate; generalized feedback that did not provide actionable information did not have the same impact. The difference between the interventions was significant, chi (1, N = 1993) = 124.7, P <.001. PMID- 29790867 TI - Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases: a pilot study. AB - PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18 fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV*SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS: MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r= 0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION: Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization. PMID- 29790869 TI - The effect of caffeine on the ventilatory response to hypercarbia in preterm infants. AB - BackgroundWe tested the hypotheses that caffeine therapy would increase the ventilatory response to hypercarbia in infants above the effect of maturation and those with a weaker ventilatory response to hypercarbia would be more likely to subsequently develop apnea that required treatment.MethodsInfants born at less than 34 weeks of gestation underwent a steady-state hypercarbic challenge using 0, 2, and 4% carbon dioxide soon after birth that was repeated at weekly intervals. The results of the initial study were compared between infants who did or did not subsequently develop apnea requiring treatment with caffeine.ResultsTwenty-six infants born at a median gestation of 32 (range 31-33) weeks were assessed. Caffeine administration was associated with an increase in CO2 sensitivity, and the mean increase was 15.3 (95% CI: 1-30) ml/kg/min/% CO2. Fourteen infants subsequently developed apnea treated with caffeine. After controlling for gestational age and birth weight, they had significantly lower carbon dioxide sensitivity at their initial study compared with those who did not require treatment.ConclusionCaffeine administration was associated with an increase in the ventilatory response to hypercarbia. An initial weaker ventilatory response to hypercarbia was associated with the subsequent development of apnea requiring treatment with caffeine. PMID- 29790868 TI - Altered prefrontal correlates of monetary anticipation and outcome in chronic pain. AB - Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain. PMID- 29790871 TI - Phenotypic expansion illuminates multilocus pathogenic variation. AB - PurposeMultilocus variation-pathogenic variants in two or more disease genes-can potentially explain the underlying genetic basis for apparent phenotypic expansion in cases for which the observed clinical features extend beyond those reported in association with a "known" disease gene.MethodsAnalyses focused on 106 patients, 19 for whom apparent phenotypic expansion was previously attributed to variation at known disease genes. We performed a retrospective computational reanalysis of whole-exome sequencing data using stringent Variant Call File filtering criteria to determine whether molecular diagnoses involving additional disease loci might explain the observed expanded phenotypes.ResultsMultilocus variation was identified in 31.6% (6/19) of families with phenotypic expansion and 2.3% (2/87) without phenotypic expansion. Intrafamilial clinical variability within two families was explained by multilocus variation identified in the more severely affected sibling.ConclusionOur findings underscore the role of multiple rare variants at different loci in the etiology of genetically and clinically heterogeneous cohorts. Intrafamilial phenotypic and genotypic variability allowed a dissection of genotype-phenotype relationships in two families. Our data emphasize the critical role of the clinician in diagnostic genomic analyses and demonstrate that apparent phenotypic expansion may represent blended phenotypes resulting from pathogenic variation at more than one locus.Genetics in Medicine advance online publication, 26 April 2018; doi:10.1038/gim.2018.33. PMID- 29790870 TI - Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities. AB - PURPOSE: Infants admitted to a level IV neonatal intensive care unit (NICU) who do not survive early childhood are a population that is probably enriched for rare genetic disease; we therefore characterized their genetic diagnostic evaluation. METHODS: This is a retrospective analysis of infants admitted to our NICU between 1 January 2011 and 31 December 2015 who were deceased at the time of records review, with age at death less than 5 years. RESULTS: A total of 2,670 infants were admitted; 170 later died. One hundred six of 170 (62%) had an evaluation for a genetic or metabolic disorder. Forty-seven of 170 (28%) had laboratory-confirmed genetic diagnoses, although 14/47 (30%) diagnoses were made postmortem. Infants evaluated for a genetic disorder spent more time in the NICU (median 13.5 vs. 5.0 days; p = 0.003), were older at death (median 92.0 vs. 17.5 days; p < 0.001), and had similarly high rates of redirection of care (86% vs. 79%; p = 0.28). CONCLUSION: Genetic disorders were suspected in many infants but found in a minority. Approximately one-third of diagnosed infants died before a laboratory-confirmed genetic diagnosis was made. This highlights the need to improve genetic diagnostic evaluation in the NICU, particularly to support end-of life decision making. PMID- 29790872 TI - Genomic sequencing identifies secondary findings in a cohort of parent study participants. AB - PurposeClinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability.MethodsExome/genome sequencing and analysis of 789 "unaffected" parents was performed.ResultsPathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the American College of Medical Genetics and Genomics. These 25 individuals self-reported either relevant clinical diagnoses (5); relevant family history or symptoms (13); or no relevant family history, symptoms, or clinical diagnoses (7). A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate pairs (n = 365) to identify cases in which both parents were carriers for the same recessive disease, yielding three such cases (0.8%), two of which had children with the relevant recessive disease. Four participants had two findings (one carrier and one noncarrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings.ConclusionWe provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design and implementation of research and clinical sequencing efforts to identify such findings.Genetics in Medicine advance online publication, 12 April 2018; doi:10.1038/gim.2018.53. PMID- 29790873 TI - Diversity of genetic events associated with MLH1 promoter methylation in Lynch syndrome families with heritable constitutional epimutation. AB - PurposeConstitutional epimutations are an alternative to genetic mutations in the etiology of genetic diseases. Some of these epimutations, termed secondary, correspond to the epigenetic effects of cis-acting genetic defects transmitted to the offspring following a Mendelian inheritance pattern. In Lynch syndrome, a few families with such apparently heritable MLH1 epimutations have been reported so far.MethodsWe designed a long-range polymerase chain reaction next-generation sequencing strategy to screen MLH1 entire gene and applied it to 4 French families with heritable epimutations and 10 additional patients with no proven transmission of their epimutations.ResultsThis strategy successfully detected the insertion of an Alu element in MLH1 coding sequence in one family. Two previously unreported MLH1 variants were also identified in other epimutation carriers: a nucleotide substitution within intron 1 and a single-nucleotide deletion in the 5'-UTR. Detection of a partial MLH1 duplication in another family required multiplex ligation-dependent probe amplification technology. We demonstrated the segregation of these variants with MLH1 methylation and studied the functional consequences of these defects on transcription.ConclusionThis is the largest cohort of patients with MLH1 secondary epimutations associated with a broad spectrum of genetic defects. This study provides further insight into the complexity of molecular mechanisms leading to secondary epimutations.GENETICS in MEDICINE advance online publication, 12 April 2018; doi:10.1038/gim.2018.47. PMID- 29790874 TI - Point-of-care whole-exome sequencing of idiopathic male infertility. AB - PURPOSE: Nonobstructive azoospermia (NOA) affects 1% of the male population; however, despite state-of-the-art clinical assessment, for most patients the cause is unknown. We capitalized on an analysis of multiplex families in the Middle East to identify highly penetrant genetic causes. METHODS: We used whole exome sequencing (WES) in 8 consanguineous families and combined newly discovered genes with previously reported ones to create a NOA gene panel, which was used to identify additional variants in 75 unrelated idiopathic NOA subjects and 74 fertile controls. RESULTS: In five of eight families, we identified rare deleterious recessive variants in CCDC155, NANOS2, SPO11, TEX14, and WNK3 segregating with disease. These genes, which are novel to human NOA, have remarkable testis-specific expression, and murine functional evidence supports roles for them in spermatogenesis. Among 75 unrelated NOA subjects, we identified 4 (~5.3%) with additional recessive variants in these newly discovered genes and 6 with deleterious variants in previously reported NOA genes, yielding an overall genetic etiology for 13.3% subjects versus 0 fertile controls (p = 0.001). CONCLUSION: NOA affects millions of men, many of whom remain idiopathic despite extensive laboratory evaluation. The genetic etiology for a substantial fraction of these patients (>50% familial and >10% sporadic) may be discovered by WES at the point of care. PMID- 29790875 TI - Visible light induced electropolymerization of suspended hydrogel bioscaffolds in a microfluidic chip. AB - The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell based units for advanced biomedical studies, e.g., for 3D bio-models or bio actuators in the future. PMID- 29790876 TI - Novel chemiluminescent immunochromatographic assay using a dual-readout signal probe for multiplexed detection of pesticide residues. AB - A novel immunochromatographic assay (ICA) using a dual-readout signal probe was developed for multiplexed detection of pesticide residues by adopting methyl parathion and fenpropathrin as model analytes. Luminol-reduced Au nanoparticles (LRAuNPs) were synthesized and utilized in the proposed ICA platform as a colorimetric/chemiluminescent (CL) dual-readout probe. The methyl parathion antibody and fenpropathrin antibody were tagged with the prepared LRAuNPs to conduct spatially-resolved multiplexed detection. After the occurrence of two immunoreactions on the test strip, the probes were captured by the immobilized antigens on the two test zones. The red color resulting from the accumulation of captured LRAuNPs was adopted as the visual and semi-quantitative readout. For the sensitive quantitative detection of the analytes, the CL signals caused by the luminophore in the LRAuNPs were collected after triggering the luminol-H2O2 CL reaction. Under the optimal conditions, the detection limits for methyl parathion and fenpropathrin were 0.17 ng mL-1 and 0.10 ng mL-1 (S/N = 3), respectively. The whole procedure for ICA was completed within 15 min. The present ICA protocol was successfully applied for detection of pesticide residues in spiked traditional Chinese medicine samples. This dual-readout ICA platform showed merits such as low cost, time efficiency, easy operation and high sensitivity. Its application potential has been demonstrated in the rapid screening and field detection of multiple pesticide residues. PMID- 29790877 TI - Two-dimensional porous cuprous oxide nanoplatelets derived from metal-organic frameworks (MOFs) for efficient photocatalytic dye degradation under visible light. AB - Bottom-up synthesis is a promising method to design and control the morphology of metal-organic frameworks (MOFs). Here, square shaped two-dimensional (2D) MOF nanoplatelets with a thickness of ~80 nm and a lateral dimension of 4-6 MUm were successfully synthesized through a facile solvothermal treatment of Cu(NO3)2 and 4,4'-bipyridine in the presence of polyvinyl pyrrolidone (PVP). The growth of a cross-weaved structure assembled via 1D chains linked with 4,4'-bipyridine along the layer stacking direction was hindered by PVP, resulting in a high-aspect ratio of the nanoplatelets. Subsequent annealing treatment converted the Cu-based MOFs into porous N-doped Cu2O/carbon composites, retaining the 2D square morphology. This annealed product showed a higher performance in the degradation of methyl orange under visible light compared to previously reported Cu2O composites. By using a small amount of the catalyst, the degradation rate could reach up to 2.5 mg min-1 gcat-1 as a result of the efficient absorption of visible light and high surface area of the porous catalysts. PMID- 29790879 TI - Exploring matrix effects and quantifying organic additives in hydraulic fracturing associated fluids using liquid chromatography electrospray ionization mass spectrometry. AB - Hydraulic fracturing (HF) operations utilize millions of gallons of water amended with chemical additives including biocides, corrosion inhibitors, and surfactants. Fluids injected into the subsurface return to the surface as wastewaters, which contain a complex mixture of additives, transformation products, and geogenic chemical constituents. Quantitative analytical methods are needed to evaluate wastewater disposal alternatives or to conduct adequate exposure assessments. However, our narrow understanding of how matrix effects change the ionization efficiency of target analytes limits the quantitative analysis of polar to semi-polar HF additives by means of liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). To address this limitation, we explored the ways in which matrix chemistry influences the ionization of seventeen priority HF additives with a modified standard addition approach. We then used the data to quantify HF additives in HF-associated fluids. Our results demonstrate that HF additives generally exhibit suppressed ionization in HF-associated fluids, though HF additives that predominantly form sodiated adducts exhibit significantly enhanced ionization in produced water samples, which is largely the result of adduct shifting. In a preliminary screening, we identified glutaraldehyde and 2-butoxyethanol along with homologues of benzalkonium chloride (ADBAC), polyethylene glycol (PEG), and polypropylene glycol (PPG) in HF-associated fluids. We then used matrix recovery factors to provide the first quantitative measurements of individual homologues of ADBAC, PEG, and PPG in HF-associated fluids ranging from mg L-1 levels in hydraulic fracturing fluid to low MUg L-1 levels in PW samples. Our approach is generalizable across sample types and shale formations and yields important data to evaluate wastewater disposal alternatives or implement exposure assessments. PMID- 29790889 TI - Strong-coupling theory of counterions between symmetrically charged walls: from crystal to fluid phases. AB - We study thermal equilibrium of classical pointlike counterions confined between symmetrically charged walls at distance d. At very large couplings when the counterion system is in its crystal phase, a harmonic expansion of particle deviations is made around the bilayer positions, with a free lattice parameter determined from a variational approach. For each of the two walls, the harmonic expansion implies an effective one-body potential at the root of all observables of interest in our Wigner strong-coupling expansion. Analytical results for the particle density profile and the pressure are in good agreement with numerical Monte Carlo data, for small as well as intermediate values of d comparable with the Wigner lattice spacing. While the strong-coupling theory is extended to the fluid regime by using the concept of a correlation hole, the Wigner calculations appear trustworthy for all electrostatic couplings investigated. Our results significantly extend the range of accuracy of analytical equations of state for strongly interacting charged planar interfaces. PMID- 29790897 TI - Six cycles of R-CHOP-21 are not inferior to eight cycles for treatment of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Population-based Study. PMID- 29790899 TI - Advances in the systemic treatment of melanoma brain metastases. AB - Of the solid tumor types that metastasize to the brain, melanoma has the highest propensity to form brain metastases. In addition, much remains unknown regarding the pathophysiology involved in melanoma cell extravasation through the blood brain barrier, which enables interactions with the microenvironment, and melanoma cell transcriptomic responses to brain-specific cues. However, recent developments in targeted therapy and immunotherapy have generated considerable optimism regarding the treatment of metastatic melanoma. Although robust efficacy data exist on systemic therapy treatment of extracranial melanoma, data in the setting of melanoma brain metastases (MBM) are limited, primarily because patients with MBM are typically excluded from clinical trials. However, several clinical trials focusing on patients with MBM are now complete, and more are underway. Clinical evaluation of serine/threonine-protein kinase B-Raf inhibition in combination with MEK inhibition for MBM produced intracranial response rates of close to 60%, suggesting that inhibition of the mitogen-activated protein kinase pathway has the potential to further improve MBM outcomes. For immunotherapy, there is now increasing evidence that checkpoint inhibitors may also be effective in MBM with a high rate of durable intracranial responses observed with combination therapy. Furthermore, radiotherapy-particularly MBM treatment with mainstay stereotactic radiosurgery-appears to be safe and effective when combined with systemic therapy. Finally, evolving magnetic resonance imaging capabilities have inspired new approaches to the measurement of tumor burden and treatment responses. This review evaluates current published evidence describing MBM as a multifaceted disease and presents an overview of currently available and investigational treatments for patients with MBM. PMID- 29790900 TI - GSCALite: a web server for gene set cancer analysis. AB - Summary: The availability of cancer genomic data makes it possible to analyze genes related to cancer. Cancer is usually the result of a set of genes and the signal of a single gene could be covered by background noise. Here, we present a web server named Gene Set Cancer Analysis (GSCALite) to analyze a set of genes in cancers with the following functional modules. (i) Differential expression in tumor versus normal, and the survival analysis; (ii) Genomic variations and their survival analysis; (iii) Gene expression associated cancer pathway activity; (iv) miRNA regulatory network for genes; (v) Drug sensitivity for genes; (vi) Normal tissue expression and eQTL for genes. GSCALite is a user-friendly web server for dynamic analysis and visualization of gene set in cancer and drug sensitivity correlation, which will be of broad utilities to cancer researchers. Availability and implementation: GSCALite is available on http://bioinfo.life.hust.edu.cn/web/GSCALite/. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790898 TI - EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in triple negative breast cancer. AB - Breast cancer is one of the most common malignancies in women. ERalpha, PR, and HER2 triple negative breast cancer (TNBC) is the current research focus because of the lack of effective targeted therapies. In our study, lentivirus systems were used to overexpress EZH2 and miR-1301 in TNBC cell lines. Western blot analysis and RT-qPCR were used to detect the protein and microRNA levels. The TCGA and Kaplan Meier plotter databases were used to analyze the EZH2 and miR 1301 expression levels in breast cancer. The effect of miR-1301 overexpression on cell proliferation, migration and colony formation were determined by using the sulforhodamine B (SRB) assay, wound healing assay and colony formation assay, respectively. Furthermore, an xenograft mouse model was used to investigate the function of miR-1301 overexpression in vivo. Finally, dual luciferase reporter assay was used to verify the binding site of EZH2 and miR-1301. We found that EZH2 induced the expression of miR-1301 in two TNBC cell lines, HCC1937 and HCC1806. Overexpression of miR-1301 suppressed TNBC cell proliferation, migration and colony formation, as well as the xenograft tumor growth in immunodeficient mice. Interestingly, miR-1301 inhibited the expression of EZH2 by binding to the 3'-UTR of EZH2 gene. These data suggest that EZH2 induces the expression of miR 1301 as a negative feedback control mechanism in TNBC. PMID- 29790901 TI - PARPi related toxicities: do we need more appropriate instruments to evaluate it? PMID- 29790902 TI - Combining probabilistic alignments with read pair information improves accuracy of split-alignments. AB - Motivation: Split-alignments provide base-pair-resolution evidence of genomic rearrangements. In practice, they are found by first computing high-scoring local alignments, parts of which are then combined into a split-alignment. This approach is challenging when aligning a short read to a large and repetitive reference, as it tends to produce many spurious local alignments leading to ambiguities in identifying the correct split-alignment. This problem is further exacerbated by the fact that rearrangements tend to occur in repeat-rich regions. Results: We propose a split-alignment technique that combats the issue of ambiguous alignments by combining information from probabilistic alignment with positional information from paired-end reads. We demonstrate that our method finds accurate split-alignments, and that this translates into improved performance of variant-calling tools that rely on split-alignments. Availability and implementation: An open-source implementation is freely available at: https://bitbucket.org/splitpairedend/last-split-pe. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790903 TI - New formulation, new drug? The importance of assessing the safety of new supportive care formulations in oncology. PMID- 29790904 TI - Exploring drug space with ChemMaps.com. AB - Motivation: Easily navigating chemical space has become more important due to the increasing size and diversity of publicly-accessible databases such as DrugBank, ChEMBL or Tox21. To do so, modelers typically rely on complex projection techniques using molecular descriptors computed for all the chemicals to be visualized. However, the multiple cheminformatics steps required to prepare, characterize, compute and explore those molecules, are technical, typically necessitate scripting skills, and thus represent a real obstacle for non specialists. Results: We developed the ChemMaps.com webserver to easily browse, navigate and mine chemical space. The first version of ChemMaps.com features more than 8000 approved, in development, and rejected drugs, as well as over 47 000 environmental chemicals. Availability and implementation: The webserver is freely available at http://www.chemmaps.com. PMID- 29790905 TI - The hard road to patient-centered care: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer? PMID- 29790906 TI - bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens. AB - Summary: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings among similar sequences in the barcode library in a statistically principled manner, and be computationally efficient. Herein we present bcSeq, an open source R package that implements a fast and parallelized algorithm for mapping high-throughput sequencing reads to a barcode library while tolerating sequencing error. The algorithm uses a Trie data structure for speed and resolves ambiguous mappings by using a statistical sequencing error model based on Phred scores for each read. Availability and implementation: The package source code and an accompanying tutorial are available at http://bioconductor.org/packages/bcSeq/. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790907 TI - Application of network smoothing to glycan LC-MS profiling. AB - Motivation: Glycosylation is one of the most heterogeneous and complex protein post-translational modifications. Liquid chromatography coupled mass spectrometry (LC-MS) is a common high throughput method for analyzing complex biological samples. Accurate study of glycans require high resolution mass spectrometry. Mass spectrometry data contains intricate sub-structures that encode mass and abundance, requiring several transformations before it can be used to identify biological molecules, requiring automated tools to analyze samples in a high throughput setting. Existing tools for interpreting the resulting data do not take into account related glycans when evaluating individual observations, limiting their sensitivity. Results: We developed an algorithm for assigning glycan compositions from LC-MS data by exploring biosynthetic network relationships among glycans. Our algorithm optimizes a set of likelihood scoring functions based on glycan chemical properties but uses network Laplacian regularization and optionally prior information about expected glycan families to smooth the likelihood and thus achieve a consistent and more representative solution. Our method was able to identify as many, or more glycan compositions compared to previous approaches, and demonstrated greater sensitivity with regularization. Our network definition was tailored to N-glycans but the method may be applied to glycomics data from other glycan families like O-glycans or heparan sulfate where the relationships between compositions can be expressed as a graph. Availability and implementation Built Executable: http://www.bumc.bu.edu/msr/glycresoft/ and Source Code: https://github.com/BostonUniversityCBMS/glycresoft. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790908 TI - Grass-legume mixtures sustain strong yield advantage over monocultures under cool maritime growing conditions over a period of 5 years. AB - Background and Aims: Grassland-based livestock systems in cool maritime regions are commonly dominated by grass monocultures receiving relatively high levels of fertilizer. The current study investigated whether grass-legume mixtures can improve the productivity, resource efficiency and robustness of yield persistence of cultivated grassland under extreme growing conditions over a period of 5 years. Methods: Monocultures and mixtures of two grasses (Phleum pratense and Festuca pratensis) and two legumes (Trifolium pratense and Trifolium repens), one of which was fast establishing and the other temporally persistent, were sown in a field trial. Relative abundance of the four species in the mixtures was systematically varied at sowing. The plots were maintained under three N levels (20, 70 and 220 kg N ha-1 year-1) and harvested twice a year for five consecutive years. Yields of individual species and interactions between all species present were modelled to estimate the species diversity effects. Key Results: Significant positive diversity effects in all individual years and averaged across the 5 years were observed. Across years, the four-species equi-proportional mixture was 71 % (N20: 20 kg N ha-1 year-1) and 51 % (N70: 70 kg N ha-1 year-1) more productive than the average of monocultures, and the highest yielding mixture was 36 % (N20) and 39 % (N70) more productive than the highest yielding monoculture. Importantly, diversity effects were also evident at low relative abundances of either species group, grasses or legumes in the mixture. Mixtures suppressed weeds significantly better than monocultures consistently during the course of the experiment at all N levels. Conclusions: The results show that even in the less productive agricultural systems in the cool maritime regions grass-legume mixtures can contribute substantially and persistently to a more sustainable agriculture. Positive grass-legume interactions suggest that symbiotic N2 fixation is maintained even under these marginal conditions, provided that adapted species and cultivars are used. PMID- 29790909 TI - EBIC: an evolutionary-based parallel biclustering algorithm for pattern discovery. AB - Motivation: Biclustering algorithms are commonly used for gene expression data analysis. However, accurate identification of meaningful structures is very challenging and state-of-the-art methods are incapable of discovering with high accuracy different patterns of high biological relevance. Results: In this paper, a novel biclustering algorithm based on evolutionary computation, a sub-field of artificial intelligence, is introduced. The method called EBIC aims to detect order-preserving patterns in complex data. EBIC is capable of discovering multiple complex patterns with unprecedented accuracy in real gene expression datasets. It is also one of the very few biclustering methods designed for parallel environments with multiple graphics processing units. We demonstrate that EBIC greatly outperforms state-of-the-art biclustering methods, in terms of recovery and relevance, on both synthetic and genetic datasets. EBIC also yields results over 12 times faster than the most accurate reference algorithms. Availability and implementation: EBIC source code is available on GitHub at https://github.com/EpistasisLab/ebic. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790910 TI - SoS Notebook: an interactive multi-language data analysis environment. AB - Motivation: Complex bioinformatic data analysis workflows involving multiple scripts in different languages can be difficult to consolidate, share and reproduce. An environment that streamlines the entire processes of data collection, analysis, visualization and reporting of such multi-language analyses is currently lacking. Results: We developed Script of Scripts (SoS) Notebook, a web-based notebook environment that allows the use of multiple scripting language in a single notebook, with data flowing freely within and across languages. SoS Notebook enables researchers to perform sophisticated bioinformatic analysis using the most suitable tools for different parts of the workflow, without the limitations of a particular language or complications of cross-language communications. Availability and implementation: SoS Notebook is hosted at http://vatlab.github.io/SoS/ and is distributed under a BSD license. PMID- 29790911 TI - PANDA-view: an easy-to-use tool for statistical analysis and visualization of quantitative proteomics data. AB - Summary: Compared with the numerous software tools developed for identification and quantification of -omics data, there remains a lack of suitable tools for both downstream analysis and data visualization. To help researchers better understand the biological meanings in their -omics data, we present an easy-to use tool, named PANDA-view, for both statistical analysis and visualization of quantitative proteomics data and other -omics data. PANDA-view contains various kinds of analysis methods such as normalization, missing value imputation, statistical tests, clustering and principal component analysis, as well as the most commonly-used data visualization methods including an interactive volcano plot. Additionally, it provides user-friendly interfaces for protein-peptide spectrum representation of the quantitative proteomics data. Availability and implementation: PANDA-view is freely available at https://sourceforge.net/projects/panda-view/. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790912 TI - Pregnancy Screening and Monitoring of Albendazole Therapy for Neurocysticercosis. PMID- 29790913 TI - Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention. AB - Background: Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. Methods: The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models. Results: Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant. Conclusions: Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. Clinical Trials Registration: NCT03245879. PMID- 29790914 TI - Females engage in stronger relationships: positive and negative effects of shrubs are more intense for Poa ligularis females than for males. AB - Background and Aims: Dioecious plants are of particular concern in view of global environmental changes because reproductive females are more sensitive to abiotic stresses, thus compromising population viability. Positive interactions with other plants may counteract the direct effects of any abiotic environmental stress, allowing them to thrive and maintain a viable population in suboptimal habitats, although this process has not been tested for dioecious species. Furthermore, almost no data are available on the outcome of such species interactions and their link with local spatial patterns and sex ratios. Methods: We set up a field experiment with Poa ligularis, a dioecious native grass from the arid grasslands of South America. We studied the interaction of male and female plants with cushion shrubs of contrasting ecological strategies. We experimentally limited direct shrub-grass competition for soil moisture and transplanted plants to evaluate the amelioration of abiotic stress by shrub canopies (i.e. sun and wind) on grasses. We also studied the distribution of naturally established female and male plants to infer process-pattern relationships. Key Results: Positive canopy effects as well as negative below ground effects were more intense for females than for males. Deep-rooted Mulinum spinosum shrubs strongly facilitated survival, growth and reproduction of P. ligularis females. Naturally established female plants tended to distribute more closely to Mulinum than co-occurring males. Female growth suffered intensive negative root competition from the shallow-rooted Senecio filaginoides shrub. Conclusions: Interactions with other plants may reduce or enhance the effect of abiotic stresses on the seemingly maladapted sex to arid environments. We found that these biased interactions are evident in the current organization of sexes in the field, confirming our experimental findings. Therefore, indirect effects of climate change on population sex ratios may be expected if benefactor species abundances are differentially affected. PMID- 29790916 TI - Diagnosis and Treatment of Neurocysticercosis: Issues That Need to Be Addressed. PMID- 29790915 TI - YAMDA: thousandfold speedup of EM-based motif discovery using deep learning libraries and GPU. AB - Motivation: Motif discovery in large biopolymer sequence datasets can be computationally demanding, presenting significant challenges for discovery in omics research. MEME, arguably one of the most popular motif discovery software, takes quadratic time with respect to dataset size, leading to excessively long runtimes for large datasets. Therefore, there is a demand for fast programs that can generate results of the same quality as MEME. Results: Here we describe YAMDA, a highly scalable motif discovery software package. It is built on Pytorch, a tensor computation deep learning library with strong GPU acceleration that is highly optimized for tensor operations that are also useful for motifs. YAMDA takes linear time to find motifs as accurately as MEME, completing in seconds or minutes, which translates to speedups over a thousandfold. Availability and implementation: YAMDA is freely available on Github (https://github.com/daquang/YAMDA). Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790917 TI - Reply to Garg et al, Smith et al, and Persichino and Miller. PMID- 29790919 TI - Antiparasitic Dosing Discrepancy in the 2017 Neurocysticercosis Guidelines. PMID- 29790918 TI - Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 messenger ribonucleic acid (mRNA) is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail. In contrast, how much SMN protein is produced at different developmental time points and in different tissues remains under-characterized. In this study, we addressed this issue by determining SMN protein expression levels at three developmental time points across six different mouse tissues and in two distinct mouse models of SMA ('severe' Taiwanese and 'intermediate' Smn2B/- mice). We found that, in healthy control mice, SMN protein expression was significantly influenced by both age and tissue type. When comparing mouse models of SMA, we found that, despite being transcribed from genetically different alleles, control SMN levels were relatively similar. In contrast, the degree of SMN depletion between tissues in SMA varied substantially over time and between the two models. These findings offer an explanation for the differential vulnerability of tissues and organs observed in SMA and further our understanding of the systemic and temporal requirements for SMN with direct relevance for developing effective therapies for SMA. PMID- 29790920 TI - Elucidating the Role of the Maternal Embryonic Leucine Zipper Kinase in Adrenocortical Carcinoma. AB - Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5-year survival rate <35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified maternal embryonic leucine zipper kinase (MELK) as 4.1-fold overexpressed in ACC compared with normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells. In vitro treatment with the MELK inhibitor, OTSSP167, resulted in a dose-dependent decrease in rates of cell proliferation, colony formation, and cell survival, with relative sensitivity of each ACC cell line based upon the level of MELK overexpression. To confirm a MELK-specific antitumorigenic effect, MELK was inhibited in H295R cells via multiple short hairpin RNAs. MELK silencing resulted in 1.9-fold decrease in proliferation, and 3- to 10-fold decrease in colony formation in soft agar and clonogenicity assays, respectively. In addition, although MELK silencing had no effect on survival in normoxia, exposure to a hypoxia resulted in a sixfold and eightfold increase in apoptosis as assessed by caspase-3 activation and TUNEL, respectively. Together these data suggest that MELK is a modulator of tumor cell growth and survival in a hypoxic microenvironment in adrenal cancer cells and support future investigation of its role as a therapeutic kinase target in patients with ACC. PMID- 29790922 TI - Artificial intelligence for melanoma diagnosis: How can we deliver on the promise? PMID- 29790921 TI - MASCOT: parameter and state inference under the marginal structured coalescent approximation. AB - Motivation: The structured coalescent is widely applied to study demography within and migration between sub-populations from genetic sequence data. Current methods are either exact but too computationally inefficient to analyse large datasets with many sub-populations, or make strong approximations leading to severe biases in inference. We recently introduced an approximation based on weaker assumptions to the structured coalescent enabling the analysis of larger datasets with many different states. We showed that our approximation provides unbiased migration rate and population size estimates across a wide parameter range. Results: We extend this approach by providing a new algorithm to calculate the probability of the state of internal nodes that includes the information from the full phylogenetic tree. We show that this algorithm is able to increase the probability attributed to the true sub-population of a node. Furthermore we use improved integration techniques, such that our method is now able to analyse larger datasets, including a H3N2 dataset with 433 sequences sampled from five different locations. Availability and implementation: The presented methods are part of the BEAST2 package MASCOT, the Marginal Approximation of the Structured COalescenT. This package can be downloaded via the BEAUti package manager. The source code is available at https://github.com/nicfel/Mascot.git. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790923 TI - Missed Opportunities to Prescribe Preexposure Prophylaxis in South Carolina, 2013 2016. AB - Introduction: Expanding use of preexposure prophylaxis (PrEP) in ways that address current racial/ethnic disparities is an important HIV prevention goal. We investigated missed opportunities to provide PrEP during healthcare visits occurring prior to HIV infection. Methods: This retrospective cohort study linked South Carolina HIV case surveillance data to 3 statewide healthcare databases. Characteristics of patients, health care visits and providers, sexually transmitted diseases (STD), and other diagnoses, were assessed for medical encounters occurring before an initial HIV diagnosis. Adjusted odds ratios were used to identify correlates of missed opportunities for PrEP provision. Results: Of 885 persons newly diagnosed during the study period, 586 (66%) had 4,029 visits to a health care facility prior to their HIV diagnosis (mean of 6.9 visits) with missed opportunities for provision of PrEP. Emergency medicine trained clinicians conducted (61%) and primary care clinicians (family practice or internal medicine) conducted. 10% of visits. 42% of visits were by persons who were uninsured or self-paid, 36% had public insurance, and 18% had commercial insurance In multivariable analyses, being female, African American, or < 30 years of age were statistically significant predictors of having prior health care visits. Among persons at least one health care visit prior to their HIV diagnosis, 28.5% had a diagnosis of gonorrhea, syphilis, or chlamydia at any visit. Conclusion: Healthcare visits occurring among persons who would benefit from provision of PrEP, especially persons with diagnosed STDs, should be leveraged to increase use of PrEP and reduce the risk of HIV acquisition. PMID- 29790924 TI - Typhoidal Salmonella serovars: ecological opportunity and the evolution of a new pathovar. AB - Typhoid and paratyphoid fever are severe systemic infections caused by human adapted typhoidal Salmonella serovars that are indistinguishable in their clinical presentation, but differ from human gastroenteritis caused by zoonotic non-typhoidal Salmonella serovars. Typhoidal Salmonella serovars evolved from ancestral gastrointestinal pathogens through genetic changes that supported a change in pathogen ecology. Typhoidal Salmonella serovars share virulence properties that were acquired through convergent evolution and therefore this group is not defined by the presence of shared virulence genes that are absent from non-typhoidal Salmonella serovars. One feature distinguishing typhoidal Salmonella serovars from gastrointestinal pathogens is their ability to avert the respiratory burst of neutrophils. Furthermore, typhoidal Salmonella serovars possess several mechanisms to moderate intestinal inflammation, which are absent from non-typhoidal Salmonella serovars. Collectively, these shared virulence mechanisms enable typhoidal Salmonella serovars to breach an intact mucosal barrier and reach the gall bladder, a new ecological niche that is important because chronic gall bladder carriage promotes disease transmission. Thus, the morbidity and mortality resulting from the severe systemic infection that enables typhoidal Salmonella serovars to reach the gall bladder is coupled to their capacity for infectious transmission, which is the principal driving force of natural selection directing the emergence of this pathovar. PMID- 29790926 TI - Bathyarchaeota: globally distributed metabolic generalists in anoxic environments. AB - Bathyarchaeota, formerly known as the Miscellaneous Crenarchaeotal Group, is a phylum of global generalists that are widespread in anoxic sediments, which host relatively high abundance archaeal communities. Until now, 25 subgroups have been identified in the Bathyarchaeota. The distinct bathyarchaeotal subgroups diverged to adapt to marine and freshwater environments. Based on the physiological and genomic evidence, acetyl-coenzyme A-centralized heterotrophic pathways of energy conservation have been proposed to function in Bathyarchaeota; these microbes are able to anaerobically utilize (i) detrital proteins, (ii) polymeric carbohydrates, (iii) fatty acids/aromatic compounds, (iv) methane (or short chain alkane) and methylated compounds, and/or (v) potentially other organic matter. Furthermore, bathyarchaeotal members have wide metabolic capabilities, including acetogenesis, methane metabolism, and dissimilatory nitrogen and sulfur reduction, and they also have potential interactions with anaerobic methane oxidizing archaea, acetoclastic methanogens and heterotrophic bacteria. These results have not only demonstrated multiple and important ecological functions of this archaeal phylum, but also paved the way for a detailed understanding of the evolution and metabolism of archaea as such. This review summarizes the recent findings pertaining to the ecological, physiological and genomic aspects of Bathyarchaeota, highlighting the vital role of this phylum in global carbon cycling. PMID- 29790925 TI - Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design. AB - Background: Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged >=65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods: Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged >=65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results: Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%-91.5%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%-73.3%). Conclusions: Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged >=65 years following introduction into a national immunization program. PMID- 29790928 TI - Using meshes for MeSH term enrichment and semantic analyses. AB - Summary: Medical Subject Headings (MeSH) is the NLM controlled vocabulary used to manually index articles for MEDLINE/PubMed. MeSH provides unique and comprehensive annotations for life science. The meshes package implements measurement of the semantic similarity of MeSH terms and gene products to help using MeSH vocabulary in knowledge mining. Enrichment analysis to extract the biological meanings from gene list, expression profile and genomic regions is also provided using MeSH annotation. Meshes supports more than 70 species and provides high quality visualization methods to help interpreting analysis results. Availability and implementation: meshes is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (https://www.bioconductor.org/packages/meshes). Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790927 TI - Syntrophin binds directly to multiple spectrin-like repeats in dystrophin and mediates binding of nNOS to repeats 16-17. AB - Mutation of the gene encoding dystrophin leads to Duchenne and Becker muscular dystrophy (DMD and BMD). Currently, dystrophin is thought to function primarily as a structural protein, connecting the muscle cell actin cytoskeleton to the extra-cellular matrix. In addition to this structural role, dystrophin also plays an important role as a scaffold that organizes an array of signaling proteins including sodium, potassium, and calcium channels, kinases, and nitric oxide synthase (nNOS). Many of these signaling proteins are linked to dystrophin via syntrophin, an adapter protein that is known to bind directly to two sites in the carboxyl terminal region of dystrophin. A search of the dystrophin sequence revealed three additional potential syntrophin binding sites (SBSs) within the spectrin-like repeat (SLR) region of dystrophin. Binding assays revealed that the site at SLR 17 bound specifically to the alpha isoform of syntrophin while the site at SLR 22 bound specifically to the beta-syntrophins. The SLR 17 alpha-SBS contained the core sequence known to be required for nNOS-dystrophin interaction. In vitro and in vivo assays indicate that alpha-syntrophin facilitates the nNOS dystrophin interaction at this site rather than nNOS binding directly to dystrophin as previously reported. The identification of multiple SBSs within the SLR region of dystrophin demonstrates that this region functions as a signaling scaffold. The signaling role of the SLR region of dystrophin will need to be considered for effective gene replacement or exon skipping based DMD/BMD therapies. PMID- 29790930 TI - A Machine Learning Recommender System to Tailor Preference Assessments to Enhance Person-Centered Care Among Nursing Home Residents. AB - Background and Objectives: Nursing homes (NHs) using the Preferences for Everyday Living Inventory (PELI-NH) to assess important preferences and provide person centered care find the number of items (72) to be a barrier to using the assessment. Research Design and Methods: Using a sample of n = 255 NH resident responses to the PELI-NH, we used the 16 preference items from the MDS 3.0 Section F to develop a machine learning recommender system to identify additional PELI-NH items that may be important to specific residents. Much like the Netflix recommender system, our system is based on the concept of collaborative filtering whereby insights and predictions (e.g., filters) are created using the interests and preferences of many users. The algorithm identifies multiple sets of "you might also like" patterns called association rules, based upon responses to the 16 MDS preferences that recommends an additional set of preferences with a high likelihood of being important to a specific resident. Results: In the evaluation of the combined apriori and logistic regression approach, we obtained a high recall performance (i.e., the ratio of correctly predicted preferences compared with all predicted preferences and nonpreferences) and high precision (i.e., the ratio of correctly predicted rules with respect to the rules predicted to be true) of 80.2% and 79.2%, respectively. Discussion and Implications: The recommender system successfully provides guidance on how to best tailor the preference items asked of residents and can support preference capture in busy clinical environments, contributing to the feasibility of delivering person centered care. PMID- 29790929 TI - miR172 downregulates the translation of cleistogamy 1 in barley. AB - Background and Aims: Floret opening in barley is induced by the swelling of the lodicule, a trait under the control of the cleistogamy1 (cly1) gene. The product of cly1 is a member of the APETALA2 (AP2) transcription factor family, which inhibits lodicule development. A sequence polymorphism at the miR172 target site within cly1 has been associated with variation in lodicule development and hence with the cleistogamous phenotype. It was unclear whether miR172 actually functions in cly1 regulation and, if it does, which miR172 gene contributes to cleistogamy. It was also interesting to explore whether miR172-mediated cly1 regulation occurs at transcriptional level or at translational level. Methods: Deep sequencing of small RNA identified the miR172 sequences expressed in barley immature spikes. miR172 genes were confirmed by computational and expression analysis. miR172 and cly1 expression profiles were determined by in situ hybridization and quantitative expression analysis. Immunoblot analysis provided the CLY1 protein quantifications. Definitive evidence of the role of miR172 in cleistogamy was provided by a transposon Ds-induced mutant of Hv-miR172a. Key Results: A small RNA analysis of the immature barley spike revealed three isomers, miR172a, b and c, of which miR172a was the most abundant. In situ hybridization analysis showed that miR172 and cly1 co-localize in the lodicule primordium, suggesting that these two molecules potentially interact with one another. Immunoblot analysis showed that the sequence polymorphism at the miR172 target site within cly1 reduced the abundance of the CLY1 protein, but not that of its transcript. In a Ds-induced mutant of Hv-miR172a, which generates no mature miR172a, the lodicules fail to grow, resulting in a very small lodicule. Conclusions: Direct evidence is presented to show that miR172a acts to reduce the abundance of the CLY1 protein, which enables open flowering in barley. PMID- 29790931 TI - GSK3beta Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels. AB - Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3beta knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3beta influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3beta and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3beta role in synaptic plasticity. PMID- 29790932 TI - SELEX Screen for Zona Pellucida-Binding DNA Aptamers. PMID- 29790933 TI - The Impact of Rotavirus Vaccines on Genotype Diversity: A Comprehensive Analysis of 2 Decades of Australian Surveillance Data. AB - Background: Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states. Methods: From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays. Results: G1P[8] was the dominant genotype nationally in the prevaccine era (1995 2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix. Conclusions: The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia. PMID- 29790934 TI - Pediatric Pituitary Adenomas: Early and Long-Term Surgical Outcome in a Series of 85 Consecutive Patients. AB - BACKGROUND: Young age has been reported as a negative prognostic factor for pituitary adenomas (PAs). They are very uncommon in children and adolescents; therefore, surgical outcomes are poorly described. OBJECTIVE: To report results of microsurgical transsphenoidal approach (MTSA) in pediatric PAs. METHODS: The study retrospectively analyzed 3040 PAs treated in our institute, according to the adenoma subtype and then divided into pediatric (<=18 yr) and adult groups (>18 yr). The average follow-up after surgery was 58 mo (n = 2906). RESULTS: In the pediatric group, the majority of adenomas were hormone-secreting (89.5%) with a female sex prevalence (78%) in prolactinomas and nonfunctioning pituitary adenomas (NFPAs); the maximum diameter of growth hormone (GH)-secreting adenomas was greater (28.1 +/- 4.1 mm) than in adults (18 +/- 0.3 mm, P = .002). Surgical remission rate at 6 mo was similar in both groups for all adenoma subtypes: 72.1% and 76% in pediatric and adult Cushing's disease, 69.3% and 59.3% in prolactinomas, 55.6% and 61% in gigantism or acromegaly, 55.6% and 61.5% in NFPAs. Recurrences after remission occurred more frequently in pediatric GH secreting adenomas compared to adults (40.0% vs 5.3%, P = .028) despite similar follow-up (38 +/- 17 and 48.1 +/- 2.2 mo, P = .7). Mortality was zero in the pediatric and 0.2% in the adult group (P = .7); major morbidity was 2.4% and 2.2%, respectively (P = .8). CONCLUSION: MTSA was safe and effective in children and adolescents as in adults, with the only exception of higher recurrence rate in pediatric GH-secreting adenomas. No complications related to young age appeared. PMID- 29790935 TI - Intake and feed utilization in two breeds of pregnant beef cows fed forages with high-fiber concentrations. AB - Hereford and Charolais beef cows (n = 24 per breed) were used to study the effect of breed and to evaluate late-cut reed canarygrass (RC) and whole-crop oats plus urea (WCO) compared with late-cut timothy (TG) with respect to feed intake and digestibility, rumination time, fecal particle size (PS) distribution, N excretion, and ruminal microbial CP production (MCP). The TG and RC were cut at flowering and WCO at hard dough stage of maturity. Cows were group-housed, 6 groups per breed, and fed 3 diets ad libitum in 3 periods. The study was designed as two 3 * 3 Latin squares amalgamated to form a 3 * 6 rectangle for each breed. All data were statistically analyzed on group level. Indigestible NDF (iNDF) and urinary creatinine excretion were used as markers to estimate apparent diet digestibility and daily urine volume, respectively. Fecal PS distribution was determined by dry sieving, and ruminal MCP synthesis was estimated based on urinary output of purine derivatives. The TG diet had a higher apparent digestibility of OM and NDF (P < 0.001) than RC and WCO, which did not differ. The TG diet resulted in the greatest daily DMI, followed by WCO and RC (P < 0.001). Intake of NDF (NDFI, kg/d and % of BW) was greatest for TG, followed by RC and WCO (P < 0.001). Rumination time per kg DMI was longest for RC (P < 0.001), and RC and WCO resulted in longest rumination time per kg NDFI (P < 0.001). The WCO diet resulted in the largest geometric mean fecal PS and proportion of large particles and in the smallest proportion of small particles, whereas the opposite was found for RC, with TG being intermediate (P < 0.001). Intakes in kg per day were higher for Charolais than for Hereford (P = 0.002), but no breed effect was detected when intake was expressed in relation to BW. Charolais ruminated longer per kg NDFI corrected for BW (P = 0.02) and had smaller mean fecal PS (P = 0.049) than Hereford. Total N excretion was highest for RC and lowest for WCO (P < 0.001). The TG diet stimulated MCP production to a greater extent than RC and WCO (P < 0.001). The results indicate that late-cut RC and WCO could be suitable alternatives to late-cut TG for ad libitum feeding of early pregnant beef cows, and that intake was associated with cow BW, but not with breed. The variations in NDF and iNDF concentrations between forage diets were reflected in their effects on intake, rumination, apparent digestibility, and fecal PS. PMID- 29790936 TI - SimExTargId: a comprehensive package for real-time LC-MS data acquisition and analysis. AB - Summary: Liquid chromatography mass spectrometry (LC-MS) is the favored method for untargeted metabolomic analysis of small molecules in biofluids. Here we present SimExTargId, an open-source R package for autonomous analysis of metabolomic data and real-time observation of experimental runs. This simultaneous, fully automated and multi-threaded (optional) package is a wrapper for vendor-independent format conversion (ProteoWizard), xcms- and CAMERA- based peak-picking, MetMSLine-based pre-processing and covariate-based statistical analysis. Users are notified of detrimental instrument drift or errors by email. Also included are two shiny applications, targetId for real-time MS2 target identification, and peakMonitor to monitor targeted metabolites. Availability and implementation: SimExTargId is publicly available under GNU LGPL v3.0 license at https://github.com/JosieLHayes/simExTargId, which includes a vignette with example data. SimExTargId should be installed on a dedicated data-processing workstation or server that is networked to the LC-MS platform to facilitate MS1 profiling of metabolomic data. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790937 TI - Test duration for water intake, ADG, and DMI in beef cattle. AB - Water is an essential nutrient, but the effect it has on performance generally receives little attention. There are few systems and guidelines for collection of water intake (WI) phenotypes in beef cattle, which makes large-scale research on WI a challenge. The Beef Improvement Federation has established guidelines for feed intake (FI) and ADG tests, but no guidelines exist for WI. The goal of this study was to determine the test duration necessary for collection of accurate WI phenotypes. To facilitate this goal, individual daily WI and FI records were collected on 578 crossbred steers for a total of 70 d using an Insentec system at the Oklahoma State University Willard Sparks Beef Research Unit. Steers were fed in five groups and were individually weighed every 14 d. Within each group, steers were blocked by BW (low and high) and randomly assigned to one of four pens containing approximately 30 steers per pen. Each pen provided 103.0 m2 of shade and included an Insentec system containing six feed bunks and one water bunk. Steers were fed a constant diet across groups and DMI was calculated using the average of weekly percent DM within group. Average FI and WI for each animal were computed for increasingly large test durations (7, 14, 21, 28, 35, 42, 49, 56, 63, and 70 d), and ADG was calculated using a regression formed from BW taken every 14 d (0, 14, 28, 42, 56, and 70 d). Intervals for all traits were computed starting from both the beginning (day 0) and the end of the testing period (day 70). Pearson and Spearman correlations were computed for phenotypes from each shortened test period and for the full 70-d test. Minimum test duration was determined when the Pearson correlations were greater than 0.95 for each trait. Our results indicated that minimum test duration for WI, DMI, and ADG were 35, 42, and 70 d, respectively. No comparable studies exist for WI; however, our results for FI and ADG are consistent with those in the literature. Although further testing in other populations of cattle and areas of the country should take place, our results suggest that WI phenotypes can be collected concurrently with DMI, without extending test duration, even if following procedures for decoupled intake and gain tests. PMID- 29790939 TI - Nextstrain: real-time tracking of pathogen evolution. AB - Summary: Understanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualization platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, open to health professionals, epidemiologists, virologists and the public alike. Availability and implementation: All code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org. PMID- 29790938 TI - The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells. AB - Mature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids. PMID- 29790940 TI - PyCoTools: a Python toolbox for COPASI. AB - Motivation: COPASI is an open source software package for constructing, simulating and analyzing dynamic models of biochemical networks. COPASI is primarily intended to be used with a graphical user interface but often it is desirable to be able to access COPASI features programmatically, with a high level interface. Results: PyCoTools is a Python package aimed at providing a high level interface to COPASI tasks with an emphasis on model calibration. PyCoTools enables the construction of COPASI models and the execution of a subset of COPASI tasks including time courses, parameter scans and parameter estimations. Additional 'composite' tasks which use COPASI tasks as building blocks are available for increasing parameter estimation throughput, performing identifiability analysis and performing model selection. PyCoTools supports exploratory data analysis on parameter estimation data to assist with troubleshooting model calibrations. We demonstrate PyCoTools by posing a model selection problem designed to show case PyCoTools within a realistic scenario. The aim of the model selection problem is to test the feasibility of three alternative hypotheses in explaining experimental data derived from neonatal dermal fibroblasts in response to TGF-beta over time. PyCoTools is used to critically analyze the parameter estimations and propose strategies for model improvement. Availability and implementation: PyCoTools can be downloaded from the Python Package Index (PyPI) using the command 'pip install pycotools' or directly from GitHub (https://github.com/CiaranWelsh/pycotools). Documentation at http://pycotools.readthedocs.io. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 29790942 TI - Exposing the Science in Citizen Science: Fitness to Purpose and Intentional Design. AB - Citizen science is a growing phenomenon. With millions of people involved and billions of in-kind dollars contributed annually, this broad extent, fine grain approach to data collection should be garnering enthusiastic support in the mainstream science and higher education communities. However, many academic researchers demonstrate distinct biases against the use of citizen science as a source of rigorous information. To engage the public in scientific research, and the research community in the practice of citizen science, a mutual understanding is needed of accepted quality standards in science, and the corresponding specifics of project design and implementation when working with a broad public base. We define a science-based typology focused on the degree to which projects deliver the type(s) and quality of data/work needed to produce valid scientific outcomes directly useful in science and natural resource management. Where project intent includes direct contribution to science and the public is actively involved either virtually or hands-on, we examine the measures of quality assurance (methods to increase data quality during the design and implementation phases of a project) and quality control (post hoc methods to increase the quality of scientific outcomes). We suggest that high quality science can be produced with massive, largely one-off, participation if data collection is simple and quality control includes algorithm voting, statistical pruning, and/or computational modeling. Small to mid-scale projects engaging participants in repeated, often complex, sampling can advance quality through expert-led training and well-designed materials, and through independent verification. Both approaches-simplification at scale and complexity with care-generate more robust science outcomes. PMID- 29790941 TI - ASaiM: a Galaxy-based framework to analyze microbiota data. AB - Background: New generations of sequencing platforms coupled to numerous bioinformatics tools have led to rapid technological progress in metagenomics and metatranscriptomics to investigate complex microorganism communities. Nevertheless, a combination of different bioinformatic tools remains necessary to draw conclusions out of microbiota studies. Modular and user-friendly tools would greatly improve such studies. Findings: We therefore developed ASaiM, an Open Source Galaxy-based framework dedicated to microbiota data analyses. ASaiM provides an extensive collection of tools to assemble, extract, explore, and visualize microbiota information from raw metataxonomic, metagenomic, or metatranscriptomic sequences. To guide the analyses, several customizable workflows are included and are supported by tutorials and Galaxy interactive tours, which guide users through the analyses step by step. ASaiM is implemented as a Galaxy Docker flavour. It is scalable to thousands of datasets but also can be used on a normal PC. The associated source code is available under Apache 2 license at https://github.com/ASaiM/framework and documentation can be found online (http://asaim.readthedocs.io). Conclusions: Based on the Galaxy framework, ASaiM offers a sophisticated environment with a variety of tools, workflows, documentation, and training to scientists working on complex microorganism communities. It makes analysis and exploration analyses of microbiota data easy, quick, transparent, reproducible, and shareable. PMID- 29790943 TI - Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures. AB - Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org. PMID- 29790944 TI - The reducing clade IIb polyketide synthase PKS14 acts as a virulence determinant of the entomopathogenic fungus Beauveria bassiana. AB - The reducing clade IIb polyketide synthase gene, pks14, is preserved throughout the evolution of entomopathogenic fungi. We examined the functions of pks14 in Beauveria bassiana using targeted gene disruption, and pks14 disruption was verified by Southern blot and PCR analyses. The radial growth, cell dry weight and conidial germination of Deltapks14 were comparable to that of the wild type. Our sequence and gene expression analyses of the pks14 biosynthetic cluster demonstrated: (i) cotranscription and constitutive expression of nearly all the genes of the aforementioned cluster including the C2H2 zinc finger transcription regulator gene, but not pks14 and the cytochrome P450 gene; (ii) expression of the pks14 gene in the insect-containing culture condition only; and (iii) a KAR9 like gene in direct proximity with pks14 is the only gene showing co-regulation. The Deltapks14-infected Spodoptera exigua larvae survived significantly longer than those infected by the wild type, indicating a marked reduction in the virulence of Deltapks14 against the insect. LT50 of Deltapks14 was increased by 1.55 days. Hyphal body formation was decreased in the hemolymph of insects infected by Deltapks14 as compared with those inoculated by the wild type. Our results suggest that PKS14-catalyzed polyketide enhances virulence and pathogenicity of B. bassiana on insects. PMID- 29790946 TI - A microbial endocrinology-based simulated small intestinal medium for the evaluation of neurochemical production by gut microbiota. AB - Microbial endocrinology represents the union of microbiology and neurobiology and is concerned with the ability of neurochemicals to serve as an evolutionary-based language between host and microbiota in health and disease. The recognition that microorganisms produce, modify and respond to the same neurochemicals utilized in the various signaling pathways of their mammalian hosts is increasingly being recognized as a mechanism by which the host and microbiota may interact to influence the progression of infectious disease as well as influence behavior through the microbiota-gut-brain axis. While the capacity for bacteria to produce neurochemicals has been recognized for decades, the degree to which this occurs in the environment of the gastrointestinal tract is still poorly understood. By combining techniques used in analytic chemistry, food science and environmental microbiology, a novel culture-based method was developed which generates a medium utilizing animal feed which resembles the contents of the small intestine. The usage of this medium allows for the in vitro growth of bacteria native to the gastrointestinal tract in an environment that is reflective of the small intestinal host-based milieu. We describe a detailed protocol for the preparation of this medium and the quantification of neurochemicals by microorganisms grown therein. Catecholamines including dopamine and its precursor L-3,4 dihydroxyphenalanine (L-DOPA) as well as biogenic amines including tyramine and its precursor tyrosine, serve as prototypical examples of neurochemicals that are quantifiable with the methods described herein. PMID- 29790945 TI - The effects of protein supplementation of fall calving beef cows on pre- and postpartum plasma insulin, glucose and IGF-I, and postnatal growth and plasma insulin and IGF-I of calves. AB - Fall calving (September to October) cows (n = 189 calvings in 5 replications; body weight [BW] = 626 +/- 6 kg, body condition score [BCS] = 4.76 +/- 0.06) grazing native dormant range were used to determine the effects of protein supplementation on performance and endocrine function of cows and calves. Cows were individually fed either a control (CON; 1.82 kg/d of 38% crude protein [CP]) or restricted (RES; 0.2 kg/d of 8% CP) protein supplement from mid-November to mid-March for 6 consecutive years. During each year, cows were reassigned dietary treatments according to calving date and BCS, and half of the CON and half of the RES cows remained on the same diets as the previous year and the other halves were assigned to the other diet. Statistical analyses were performed with the general linear model procedure utilizing a 2 * 2 factorial arrangement and a complete randomized design. Cows on CON diets lost less BW from November to January compared with RES cows (-25.9 +/- 2.6 and -45.0 +/- 2.6 kg, respectively; P < 0.001). Protein supplementation increased plasma concentrations of insulin of CON compared with RES cows during treatment (P < 0.05). Calf birth weight did not differ between prenatal supplemention of CON and RES (P = 0.87). A prenatal * postnatal effect was detected for BW of calves; prenatal RES and postnatal CON calves (RES-CON; 189.4 +/- 4.2, P = 0.05) had greater 205-d adjusted weaning weights compared with prenatal RES and postnatal RES (RES-RES) and prenatal CON and postnatal RES (CON-RES) calves (163.0 +/- 4.2 and 177.8 +/- 4.2 kg, respectively). There was a prenatal * postnatal effect on gain of calves from January to weaning (P = 0.05); RES-CON gained more than RES-RES and CON-RES calves. Adjusted yearling 365-d BW was least (P = 0.02) for RES-RES calves. Prenatal protein supplementation of cows decreased (P = 0.03) final BW of calves at harvest (23 mo). Prenatal and postnatal supplementation of cows did not influence carcass characteristics of calves (P > 0.10). In conclusion, increasing protein supplementation of fall calving beef cows from November to March, during breeding and early pregnancy, reduced BW loss of cows, decreased the interval from calving to pregnancy, increased plasma concentrations of insulin in December, January, and March, and increased plasma insulin-like growth factor-I in December without alteration in pregnancy rate. Reduced protein supplementation prenatally increased BW of calves at harvest. PMID- 29790947 TI - Antibodies Against Chlamydia trachomatis and Ovarian Cancer Risk in Two Independent Populations. AB - Background: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. Methods: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. Results: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. Conclusions: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer. PMID- 29790948 TI - Cardioprotection Induced by Activation of GPER in Ovariectomized Rats With Pulmonary Hypertension. AB - Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s.c. injection of either vehicle or G1, a GPER agonist, (400 ug/kg/day) for 14 days after the onset of disease. Rats with PH exhibited exercise intolerance and cardiopulmonary alterations, including reduced pulmonary artery flow, biventricular remodeling, and left ventricular systolic and diastolic dysfunction. The magnitude of these PH-induced changes was significantly greater in OVX versus SHAM rats. G1 treatment reversed both cardiac and skeletal muscle functional aberrations caused by PH in OVX rats. G1 reversed PH-related cardiopulmonary dysfunction and exercise intolerance in female rats, a finding that may have important implications for the ongoing clinical evaluation of new drugs for the treatment of the disease in females after the loss of endogenous estrogens. PMID- 29790949 TI - Fecal microbiota composition changes after a BW loss diet in Beagle dogs. AB - In developed countries, dogs and cats frequently suffer from obesity. Recently, gut microbiota composition in humans has been related to obesity and metabolic diseases. This study aimed to evaluate changes in body composition, and gut microbiota composition in obese Beagle dogs after a 17-wk BW loss program. A total of six neutered adult Beagle dogs with an average initial BW of 16.34 +/- 1.52 kg and BCS of 7.8 +/- 0.1 points (9-point scale) were restrictedly fed with a hypocaloric, low-fat and high-fiber dry-type diet. Body composition was assessed with dual-energy X-ray absorptiometry scan, before (T0) and after (T1) BW loss program. Individual stool samples were collected at T0 and T1 for the 16S rRNA analyses of gut microbiota. Taxonomic analysis was done with amplicon-based metagenomic results, and functional analysis of the metabolic potential of the microbial community was done with shotgun metagenomic results. All dogs reached their ideal BW at T1, with an average weekly proportion of BW loss of -1.07 +/- 0.03% of starting BW. Body fat (T0, 7.02 +/- 0.76 kg) was reduced by half (P < 0.001), while bone (T0, 0.56 +/- 0.06 kg) and muscle mass (T0, 8.89 +/- 0.80 kg) remained stable (P > 0.05). The most abundant identified phylum was Firmicutes (T0, 74.27 +/- 0.08%; T1, 69.38 +/- 0.07%), followed by Bacteroidetes (T0, 12.68 +/- 0.08%; T1, 16.68 +/- 0.05%), Fusobacteria (T0, 7.45 +/- 0.02%; T1, 10.18 +/- 0.03%), Actinobacteria (T0, 4.53 +/- 0.02%; T1, 3.34 +/- 0.01%), and Proteobacteria (T0, 1.06 +/- 0.01%; T1, 1.40 +/- 0.00%). At genus level, the presence of Clostridium, Lactobacillus, and Dorea, at T1 decreased (P = 0.028), while Allobaculum increased (P = 0.046). Although the microbiota communities at T0 and T1 showed a low separation level when compared (Anosim's R value = 0.39), they were significantly biodiverse (P = 0.01). Those differences on microbiota composition could be explained by 13 genus (alpha = 0.05, linear discriminant analysis (LDA) score > 2.0). Additionally, differences between both communities could also be explained by the expression of 18 enzymes and 27 pathways (alpha = 0.05, LDA score > 2.0). In conclusion, restricted feeding of a low-fat and high fiber dry-type diet successfully modifies gut microbiota in obese dogs, increasing biodiversity with a different representation of microbial genus and metabolic pathways. PMID- 29790951 TI - Internet Use and Preventive Health Behaviors Among Couples in Later Life: Evidence from the Health and Retirement Study. AB - Background and Objectives: The aim of this study was to examine the link between internet use and preventive health behaviors. We focused on couples to examine whether there were cross-partner associations between internet use and preventive health behaviors. Research Design and Methods: The data for this study came from the 2010 and 2012 waves of the Health and Retirement Study and the sample consisted of 5,143 pairs of coupled-individuals. Preventive health behaviors included cancer screenings (mammogram and prostate tests), cholesterol tests, and flu shots. Logistic multilevel actor-partner interdependence models were employed to test the study hypotheses. Results: Internet use was associated with a higher likelihood of receiving prostate exams and cholesterol tests for husbands, net of demographic and health characteristics, and insurance status. We found that wives' internet use was associated with a higher likelihood of receiving flu shots and prostate exams for husbands, but husbands' internet use was not associated with wives' preventive health behaviors. Discussion and Implications: Research linking internet use and preventive health behaviors is important because such behaviors are associated not only with health of the older population but also with substantial reductions in health care expenditures. Our findings suggested that internet use of older adults is associated with their own preventive health behaviors, as well as their spouses' preventive health behaviors. Interventions and programs to facilitate older adults' preventive health behaviors should consider couple-based approaches. PMID- 29790950 TI - The research data management platform (RDMP): A novel, process driven, open source tool for the management of longitudinal cohorts of clinical data. AB - Background: The Health Informatics Centre at the University of Dundee provides a service to securely host clinical datasets and extract relevant data for anonymized cohorts to researchers to enable them to answer key research questions. As is common in research using routine healthcare data, the service was historically delivered using ad-hoc processes resulting in the slow provision of data whose provenance was often hidden to the researchers using it. This paper describes the development and evaluation of the Research Data Management Platform (RDMP): an open source tool to load, manage, clean, and curate longitudinal healthcare data for research and provide reproducible and updateable datasets for defined cohorts to researchers. Results: Between 2013 and 2017, RDMP tool implementation tripled the productivity of data analysts producing data releases for researchers from 7.1 to 25.3 per month and reduced the error rate from 12.7% to 3.1%. The effort on data management reduced from a mean of 24.6 to 3.0 hours per data release. The waiting time for researchers to receive data after agreeing a specification reduced from approximately 6 months to less than 1 week. The software is scalable and currently manages 163 datasets. A total 1,321 data extracts for research have been produced, with the largest extract linking data from 70 different datasets. Conclusions: The tools and processes that encompass the RDMP not only fulfil the research data management requirements of researchers but also support the seamless collaboration of data cleaning, data transformation, data summarization and data quality assessment activities by different research groups. PMID- 29790952 TI - Why, when and how should exposure be considered at the within-host scale? A modelling contribution to PRRSv infection. AB - Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore the impact on the within-host response not only of the exposure dose, but also of its duration and peak, for contrasted virulence levels. We used an integrative modelling approach of the within-host dynamics at the between-cell level. We focused on the porcine reproductive and respiratory syndrome virus, a major concern for the swine industry. We quantified the impact of exposure and virulence on the viral dynamics and immune response by global sensitivity analyses and descriptive statistics. We found that the area under the viral curve, an indicator of the infection severity, was fully determined by the exposure intensity. The infection duration increased with the strain virulence and, for a given strain, exhibited a positive linear correlation with the exposure intensity logarithm and the exposure duration. Taking into account the exposure intensity is hence necessary. Besides, representing the exposure due to contacts by a single punctual dose would tend to underestimate the infection duration. As the infection severity and duration both contribute to the pig infectiousness, a prolonged exposure of the adequate intensity would be recommended in an immuno-epidemiological context. PMID- 29790953 TI - Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice. AB - Antisense oligonucleotides that are dependent on RNase H for cleavage and subsequent degradation of complementary RNA are being developed as therapeutics. Besides the intended RNA target, such oligonucleotides may also cause degradation of unintended RNA off-targets by binding to partially complementary target sites. Here, we characterized the global effects on the mouse liver transcriptome of four oligonucleotides designed as gapmers, two targeting Apob and two targeting Pcsk9, all in different regions on their respective intended targets. This study design allowed separation of intended- and off-target effects on the transcriptome for each gapmer. Next, we used sequence analysis to identify possible partially complementary binding sites among the potential off-targets, and validated these by measurements of melting temperature and RNase H-cleavage rates. Generally, our observations were as expected in that fewer mismatches or bulges in the gapmer/transcript duplexes resulted in a higher chance of those duplexes being effective substrates for RNase H. Follow-up experiments in mice and cells show, that off-target effects can be mitigated by ensuring that gapmers have minimal sequence complementarity to any RNA besides the intended target, and that they do not have exaggerated binding affinity to the intended target. PMID- 29790955 TI - Letter: Guidelines for the Use of Electrophysiological Monitoring for Surgery of the Human Spinal Column and Spinal Cord. PMID- 29790954 TI - Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. AB - This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed. PMID- 29790957 TI - Cultivating Collaborations: Site Specific Design for Embodied Science Learning. AB - Immersion in well-designed outdoor environments can foster the habits of mind that enable critical and authentic scientific questions to take root in students' minds. Here we share two design cases in which careful, collaborative, and intentional design of outdoor learning environments for informal inquiry provide people of all ages with embodied opportunities to learn about the natural world, developing the capacity for understanding ecology and the ability to empathize, problem-solve, and reflect. Embodied learning, as facilitated by and in well designed outdoor learning environments, leads students to develop new ways of seeing, new scientific questions, new ways to connect with ideas, with others, and new ways of thinking about the natural world. Using examples from our collaborative practises as experiential learning designers, we illustrate how creating the habits of mind critical to creating scientists, science-interested, and science-aware individuals benefits from providing students spaces to engage in embodied learning in nature. We show how public landscapes designed in creative partnerships between educators, scientists, designers, and the public have potential to amplify science learning for all. PMID- 29790958 TI - Corrigendum. PMID- 29790956 TI - 5-Hydroxymethylcytosine alterations in the human postmortem brains of autism spectrum disorder. AB - Autism spectrum disorders (ASDs) include a group of syndromes characterized by impaired language, social and communication skills, in addition to restrictive behaviors or stereotypes. However, with a prevalence of 1.5% in developed countries and high comorbidity rates, no clear underlying mechanism that unifies the heterogeneous phenotypes of ASD exists. 5-hydroxymethylcytosine (5hmC) is highly enriched in the brain and recognized as an essential epigenetic mark in developmental and brain disorders. To explore the role of 5hmC in ASD, we used the genomic DNA isolated from the postmortem cerebellum of both ASD patients and age-matched controls to profile genome-wide distribution of 5hmC. We identified 797 age-dependent differentially hydroxymethylated regions (DhMRs) in the young group (age <= 18), while no significant DhMR was identified in the groups over 18 years of age. Pathway and disease association analyses demonstrated that the intragenic DhMRs were in the genes involved in cell-cell communication and neurological disorders. Also, we saw significant 5hmC changes in the larger group of psychiatric genes. Interestingly, we found that the predicted cis functions of non-coding intergenic DhMRs strikingly associate with ASD and intellectual disorders. A significant fraction of intergenic DhMRs overlapped with topologically associating domains. These results together suggest that 5hmC alteration is associated with ASD, particularly in the early development stage, and could contribute to the pathogenesis of ASD. PMID- 29790959 TI - Peripheral blood gene expression reveals an inflammatory transcriptomic signature in Friedreich's ataxia patients. AB - Transcriptional changes in Friedreich's ataxia (FRDA), a rare and debilitating recessive Mendelian neurodegenerative disorder, have been studied in affected but inaccessible tissues-such as dorsal root ganglia, sensory neurons and cerebellum in animal models or small patient series. However, transcriptional changes induced by FRDA in peripheral blood, a readily accessible tissue, have not been characterized in a large sample. We used differential expression, association with disability stage, network analysis and enrichment analysis to characterize the peripheral blood transcriptome and identify genes that were differentially expressed in FRDA patients (n = 418) compared with both heterozygous expansion carriers (n = 228) and controls (n = 93 739 individuals in total), or were associated with disease progression, resulting in a disease signature for FRDA. We identified a transcriptional signature strongly enriched for an inflammatory innate immune response. Future studies should seek to further characterize the role of peripheral inflammation in FRDA pathology and determine its relevance to overall disease progression. PMID- 29790960 TI - ComplexContact: a web server for inter-protein contact prediction using deep learning. AB - ComplexContact (http://raptorx2.uchicago.edu/ComplexContact/) is a web server for sequence-based interfacial residue-residue contact prediction of a putative protein complex. Interfacial residue-residue contacts are critical for understanding how proteins form complex and interact at residue level. When receiving a pair of protein sequences, ComplexContact first searches for their sequence homologs and builds two paired multiple sequence alignments (MSA), then it applies co-evolution analysis and a CASP-winning deep learning (DL) method to predict interfacial contacts from paired MSAs and visualizes the prediction as an image. The DL method was originally developed for intra-protein contact prediction and performed the best in CASP12. Our large-scale experimental test further shows that ComplexContact greatly outperforms pure co-evolution methods for inter-protein contact prediction, regardless of the species. PMID- 29790962 TI - In response to letter: Opioids use in ICU: a causal agent for sleep apnea, unmasking the undiagnosed sleep apnea or both in the ICU. PMID- 29790961 TI - Increased vulnerability to attentional failure during acute sleep deprivation in women depends on menstrual phase. AB - Study Objectives: To investigate sex differences in the effect of sleep deprivation on performance, accounting for menstrual phase in women. Methods: We examined alertness data from 124 healthy women and men (40 women, 84 men; aged 18 30 years) who maintained wakefulness for at least 30 hr in a laboratory setting using a constant routine protocol. Objective alertness was assessed every 2 hr using a 10 min psychomotor vigilance task. Subjective alertness was assessed every hour via the Karolinska Sleepiness Scale. Results: Women in the follicular phase of the menstrual cycle demonstrated the poorest level of performance. This poor performance was most pronounced at times corresponding to the typical sleep episode, demonstrating a window of vulnerability at night during this menstrual phase. At 24 hr awake, over 60 per cent of their responses were lapses of >500 ms and over one-third of their responses were longer lapses of at least 3 s in duration. Women in the luteal phase, however, were relatively protected from alertness failure, performing similar or better than both follicular-phase women and men. Conclusions: These results have important implications for education and intervention programs for shift workers, specifically during times of vulnerability to attentional failure that increase risk of injury. PMID- 29790965 TI - Rotavirus Vaccines: Mind Your Ps and Gs. PMID- 29790963 TI - The presenilin loop region is essential for glycogen synthase kinase 3 beta (GSK3beta) mediated functions on motor proteins during axonal transport. AB - Neurons require intracellular transport of essential components for function and viability and defects in transport has been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). One possible mechanism by which transport defects could occur is by improper regulation of molecular motors. Previous work showed that reduction of presenilin (PS) or glycogen synthase kinase 3 beta (GSK3beta) stimulated amyloid precursor protein vesicle motility. Excess GSK3beta caused transport defects and increased motor binding to membranes, while reduction of PS decreased active GSK3beta and motor binding to membranes. Here, we report that functional PS and the catalytic loop region of PS is essential for the rescue of GSK3beta-mediated axonal transport defects. Disruption of PS loop (PSDeltaE9) or expression of the non-functional PS variant, PSD447A, failed to rescue axonal blockages in vivo. Further, active GSK3beta associated with and phosphorylated kinesin-1 in vitro. Our observations together with previous work that showed that the loop region of PS interacts with GSK3beta propose a scaffolding mechanism for PS in which the loop region sequesters GSK3beta away from motors for the proper regulation of motor function. These findings are important to uncouple the complex regulatory mechanisms that likely exist for motor activity during axonal transport in vivo. PMID- 29790966 TI - TCRmodel: high resolution modeling of T cell receptors from sequence. AB - T cell receptors (TCRs), along with antibodies, are responsible for specific antigen recognition in the adaptive immune response, and millions of unique TCRs are estimated to be present in each individual. Understanding the structural basis of TCR targeting has implications in vaccine design, autoimmunity, as well as T cell therapies for cancer. Given advances in deep sequencing leading to immune repertoire-level TCR sequence data, fast and accurate modeling methods are needed to elucidate shared and unique 3D structural features of these molecules which lead to their antigen targeting and cross-reactivity. We developed a new algorithm in the program Rosetta to model TCRs from sequence, and implemented this functionality in a web server, TCRmodel. This web server provides an easy to use interface, and models are generated quickly that users can investigate in the browser and download. Benchmarking of this method using a set of nonredundant recently released TCR crystal structures shows that models are accurate and compare favorably to models from another available modeling method. This server enables the community to obtain insights into TCRs of interest, and can be combined with methods to model and design TCR recognition of antigens. The TCRmodel server is available at: http://tcrmodel.ibbr.umd.edu/. PMID- 29790967 TI - Common Genetic Basis of Eye and Pigment Loss in Two Distinct Cave Populations of the Isopod Crustacean Asellus aquaticus. AB - Repeated evolution of similar phenotypes is a widespread phenomenon found throughout the living world and it can proceed through the same or different genetic mechanisms. Cave animals with their convergent traits such as eye and pigment loss, as well as elongated appendages, are a striking example of the evolution of similar phenotypes. Yet, few cave species are amenable to genetic crossing and mapping techniques making it challenging to determine the genetic mechanisms causing their similar phenotypes. To address this limitation, we have been developing Asellus aquaticus, a freshwater isopod crustacean, as a genetic model. Many of its cave populations originate from separate colonization events and thus independently evolved their similar cave-related phenotypes which differ from the still existent ancestral-like surface populations. In our prior work, we identified genomic regions responsible for eye and pigment loss in a single cave population from Slovenia. In this study we examined another, independently evolved cave population, also from Slovenia, and asked whether the same or different genomic regions are responsible for eye and pigment loss in the two cave populations. We generated F2 and backcross hybrids with a surface population, genotyped them for the previously identified genomic regions, and performed a complementation test by crossing individuals from the two cave populations. We found out that the same genomic regions are responsible for eye and pigment loss and that at least one of the genes causing pigment loss is the same in both cave populations. Future studies will identify the actual genes and mutations, as well as examine additional cave populations to see if the same genes are commonly associated with eye and pigment loss in this species. PMID- 29790968 TI - "Macrovascular" Decompression of Dolichoectatic Vertebral Artery Causing Hemifacial Spasm Using Goretex Sling: 2-Dimensional Operative Video. AB - Hemifacial spasm is characterized by painless and involuntary spasms of the muscles supplied by the facial nerve, most commonly involving the orbicularis oculi. The most common cause of hemifacial spasm is compression of the facial nerve's root by the anterior inferior, or posterior inferior, cerebellar arteries (AICA or PICA). However, in <1% of cases, the compression can be due to a dolichoectatic vertebral artery. Microvascular decompression using Teflon patties may be sufficient when the offending artery is small (eg, AICA or PICA). However, the size and tortuosity of the vertebral artery (especially one that is dolichoectatic) may require a more robust means of decompression (ie, "macrovascular decompression"). In this operative video we demonstrate our technique for managing a patient with hemifacial spasm due to a dolicoectatic vertebral artery. We use a Goretex(r) (W.L. Gore & Associates Inc, Newark, Delaware) sling secured to the dura of the posterior petrous ridge to suspend the vertebral and posterior inferior cerebellar arteries, thereby decompressing the root entry zone of the facial nerve. Teflon felt pieces are added as a second layer of security. Key steps to this technique include: (1) visualization of the root entry zone, (2) extensive arachnoid dissection to allow adequate mobilization of the vertebral artery, 12 and (3) securing the sling in a trajectory that prevents kinking of the vertebral artery and its branches. PMID- 29790964 TI - Evidence of evolutionary history and selective sweeps in the genome of Meishan pig reveals its genetic and phenotypic characterization. AB - Background: Meishan is a pig breed indigenous to China and famous for its high fecundity. The traits of Meishan are strongly associated with its distinct evolutionary history and domestication. However, the genomic evidence linking the domestication of Meishan pigs with its unique features is still poorly understood. The goal of this study is to investigate the genomic signatures and evolutionary evidence related to the phenotypic traits of Meishan via large-scale sequencing. Results: We found that the unique domestication of Meishan pigs occurred in the Taihu Basin area between the Majiabang and Liangzhu Cultures, during which 300 protein-coding genes have underwent positive selection. Notably, enrichment of the FoxO signaling pathway with significant enrichment signal and the harbored gene IGF1R were likely associated with the high fertility of Meishan pigs. Moreover, NFKB1 exhibited strong selective sweep signals and positively participated in hyaluronan biosynthesis as the key gene of NF-kB signaling, which may have resulted in the wrinkled skin and face of Meishan pigs. Particularly, three population-specific synonymous single-nucleotide variants occurred in PYROXD1, MC1R, and FAM83G genes; the T305C substitution in the MCIR gene explained the black coat of the Meishan pigs well. In addition, the shared haplotypes between Meishan and Duroc breeds confirmed the previous Asian-derived introgression and demonstrated the specific contribution of Meishan pigs. Conclusions: These findings will help us explain the unique genetic and phenotypic characteristics of Meishan pigs and offer a plausible method for their utilization of Meishan pigs as valuable genetic resources in pig breeding and as an animal model for human wrinkled skin disease research. PMID- 29790969 TI - Microcatheter "First-Pass Effect" Predicts Acute Intracranial Artery Atherosclerotic Disease-Related Occlusion. AB - BACKGROUND: The differentiation between intracranial atherosclerotic stenosis (ICAS) and intracranial embolism as the immediate cause of acute ischemic stroke requiring endovascular therapy is important but challenging. In cases of ICAS, we often observe a phenomenon we call the microcatheter "first-pass effect," which is temporary blood flow through the occluded intracranial artery when the angiographic microcatheter is initially advanced through the site of total occlusion and immediately retrieved proximally. OBJECTIVE: To evaluate whether this microcatheter first-pass effect can be used to differentiate ICAS from intracranial embolism. METHODS: A total of 61 patients with acute ischemic stroke resulting from large intracranial artery occlusion and in whom recanalization was achieved by endovascular treatment were included in the study. The microcatheter first-pass effect was tested in these patients. The sensitivity, specificity, positive predictive values (PPV), and accuracy of the microcatheter first-pass effect for prediction of ICAS were assessed. RESULTS: The microcatheter first pass effect was more frequently observed in patients with ICAS than in those with intracranial embolism (90.9% vs 12.8%, P < .001). For identifying ICAS, sensitivity, specificity, PPV, and accuracy of the microcatheter first-pass effect were 90.9%, 87.2%, 80.0%, 88.5%, respectively. CONCLUSION: The sensitivity and PPV of the microcatheter first-pass effect are high for prediction of ICAS in patients with acute symptoms. PMID- 29790970 TI - Balloon Occlusion Testing to Assess Retinal Collateral and Predict Visual Outcomes in the Management of a Fusiform Intraorbital Ophthalmic Artery Aneurysm: Technical Note and Literature Review. AB - BACKGROUND AND IMPORTANCE: Aneurysms of the ophthalmic artery (OA) within the orbit and optic canal are extremely rare. Given the peripheral location of these aneurysms and the fact that most are fusiform, parent artery occlusion is preferred for symptomatic aneurysms. However, the impact of OA occlusion on vision is not always innocuous. Balloon occlusion testing (BOT) of the OA has the potential to gauge the possibility of visual compromise, in addition to assessing collaterals. While BOT has been assessed for carotid artery occlusion, its role in OA occlusion has not been well defined. CLINICAL PRESENTATION: We describe a patient with a 6-mm intracanalicular OA aneurysm who was treated with endovascular coil embolization of the aneurysm and occlusion of the parent artery. We performed a 30-min balloon occlusion test, in which we verified intact visual and neurological function. Collateral vascularity was confirmed. Complete occlusion was achieved and the patient recovered with intact visual and neurological function. We provide a review of literature pertaining to parent artery occlusion of OA aneurysms that occur within optic canal and orbit. A brief note on anatomy of OA and collaterals is provided. CONCLUSION: Endovascular parent artery occlusion is an effective treatment for OA aneurysms that occur in optic canal and orbit. Assessment of effect of occlusion on vision is important. BOT can assess this and provide valuable information. Recovery or preservation of visual function is highly dependent on preoperative visual status. PMID- 29790971 TI - Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia. AB - Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. Results: Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. Conclusions: Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors. PMID- 29790972 TI - Isolation and biological characterization of mesenchymal stem cells from goose dermis. AB - The skin is a natural target of stem cell research because of its large size and easy accessibility. Cutaneous mesenchymal stem cells have shown to be a promising source of various adult stem cell or progenitor cell populations, which provide an important source of stem cell-based investigation. Nowadays, much work has been done on dermal-derived mesenchymal stem cells (DMSCs) from humans, mice, sheep, and other mammals, but the literature on avian species has been rarely reported. As an animal model, the goose is an endemic species abounding in dermal tissues which is important in the global economy. In this study, we isolated and established the mesenchymal stem cell line from dermis tissue of goose, which were subcultured to passage 21 in vitro without loss of their functional integrity in terms of morphology, renewal capacity, and presence of mesenchymal stem cell markers. Cryopreservation and resuscitation were also observed in different passages. To investigate the biological characteristics of goose DMSCs, immunofluorescence, reverse transcription-polymerase chain reaction, and flow cytometry were used to detect the characteristic surface markers. Growth curves and the capacity of colony forming were performed to test the self-renew and proliferative ability. Furthermore, the DMSCs are induced to osteoblasts, adipocytes, and chondrocytes in vitro. Our results suggest that DMSCs isolated from goose embryos possess similar biological characteristics to those from other species. The methods in establishment and cultivation of goose DMSCs line demonstrated a good self-renew and expansion potential in vitro, which provided a technological platform for preserving the valuable genetic resources of poultry and a great inspiration for in vitro investigation of avian MSCs. PMID- 29790973 TI - Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins. AB - Background: Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Methods: Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P < 0.05 as significant. Results: Correlation of AlbBCG and AlbBCP was r = 0.948 (p < 0.0001), but mean difference was large. Bland-Altman plots showed greater bias at lower albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (< 1 g/L). The AlbBCG assay bias shows a good correlation with alpha-1-globulin concentrations (r = 0.758); moderate and weak correlations were observed with CRP (r = 0.729) and alpha-2-globulin (r = 0.585); we found no correlation with beta-globulin (r = 0.120) or gamma-globulin (r = -0.303). Mean aCa based on AlbBCG and AlbBCP methods were 2.34 +/- 0.15 mmol/L and 2.46 +/- 0.16 mmol/L (p < 0.01), with a mean BCG-BCP difference of -0.12. Conclusion: Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG. PMID- 29790975 TI - In Reply: Guidelines for the Use of Electrophysiological Monitoring for Surgery of the Human Spinal Column and Spinal Cord. PMID- 29790974 TI - CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins. AB - CRISPR (clustered regularly interspaced short palindromic repeats) arrays and their associated (Cas) proteins confer bacteria and archaea adaptive immunity against exogenous mobile genetic elements, such as phages or plasmids. CRISPRCasFinder allows the identification of both CRISPR arrays and Cas proteins. The program includes: (i) an improved CRISPR array detection tool facilitating expert validation based on a rating system, (ii) prediction of CRISPR orientation and (iii) a Cas protein detection and typing tool updated to match the latest classification scheme of these systems. CRISPRCasFinder can either be used online or as a standalone tool compatible with Linux operating system. All third-party software packages employed by the program are freely available. CRISPRCasFinder is available at https://crisprcas.i2bc.paris-saclay.fr. PMID- 29790976 TI - Cancer Dissemination, Hydrocephalus, and Survival After Cerebral Ventricular Entry During High-Grade Glioma Surgery: A Meta-Analysis. AB - BACKGROUND: The consequences of ventricular entry during resection of high-grade gliomas (HGG) are uncertain and often not detectable clinically. OBJECTIVE: To reveal odds of tumor dissemination, hydrocephalus, and mortality in adult patients who had ventricular entry during surgical resection of HGG. METHODS: Titles and abstracts of published journals in the NCBI/NLM PubMed and OVID EMBASE databases were searched without language restriction and systematically screened. Outcomes extracted included the odds of leptomeningeal dissemination and hydrocephalus in patients with ventricular entry during HGG resection compared to without. They were analyzed using a random-effects model to calculate summary odds ratios (sORs). Overall survival data were also compared between patients with and without ventricular entry. RESULTS: Twenty final studies with 2251 total patients were included from the 6910 retrieved. Patients with ventricular entry during HGG resection demonstrated higher odds of leptomeningeal dissemination (sOR: 3.91 [95% confidence interval (CI): 1.89-8.10]; P = .0002; 86/410 vs 57/847 patients in 9 studies) and hydrocephalus (sOR: 7.78 [95% CI: 3.77-16.05]; P < .00001; 58/431 vs 11/565 patients in 11 studies). They also had decreased survival (median survival: 16.8 vs 19.1 mo; 413 vs 322 patients in 10 studies; hazard ratio: 1.25 [95% CI: 1.05-1.48], P = .01). CONCLUSION: The association between ventricular entry during HGG resection and tumor dissemination, hydrocephalus, and decreased survival invites investigations to understand this link. Neurosurgeons and neuro-oncologists must be aware of the consequences of ventricular entry during surgery for HGG. PMID- 29790977 TI - alpha-Synuclein aggregates in labial salivary glands of idiopathic rapid eye movement sleep behavior disorder. AB - Study Objectives: To assess whether biopsy of the labial minor salivary glands safely detects phosphorylated alpha-synuclein (pAS) deposits in idiopathic rapid eye movement sleep behavior disorder (IRBD), a condition that precedes the cardinal manifestations of synuclein disorders associated with Lewy-type pathology, namely, Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Methods: In a prospective study, labial biopsy of the minor salivary glands was performed in 62 patients with IRBD, 13 patients with PD, and 10 patients with DLB who were initially diagnosed with IRBD, and in 33 controls. Aggregates of pAS were assessed by immunohistochemistry using antiserine 129-pAS antibody and the conformation-specific 5G4 antibody. Results: Sufficient biopsy material containing glandular parenchyma was obtained in all participants. Deposits of pAS were found in 31 of 62 (50%) participants with IRBD, 7 of 13 (54%) with PD, 5 of 10 (50%) with DLB, and in one of the 33 (3%) controls. Participants with IRBD, PD, and DLB with and without pAS immunoreactivity did not differ in demographic and clinical features. Adverse events were lip bruising (9.2%), swelling (6.6%), pain (2.4%), and numbness (1.7%) which were mild and transitory and did not require treatment. Conclusions: Labial minor salivary glands biopsy proved to be a safe and useful procedure to identify pAS in participants with IRBD, and in participants with PD and DLB initially diagnosed with IRBD. The biopsy provides direct histopathological evidence that IRBD represents a synucleinopathy and that could be useful for histological confirmation of synuclein pathology in PD and DLB. PMID- 29790978 TI - Mobilization of the Anterior/Posterior Inferior Cerebellar Artery on the Cerebellar Surface in Microvascular Decompression Surgery for Hemifacial Spasm: Potential Effect on Hearing Preservation. AB - BACKGROUND: The infrafloccular approach in microvascular decompression (MVD) for hemifacial spasm (HFS) reduces the risk of postoperative hearing impairment. However, location of the anterior/posterior inferior cerebellar artery (AICA/PICA) on the cerebellar surface in the surgical route requires mobilization to maintain the approach direction for the protection of hearing function. OBJECTIVE: To evaluate the effectiveness of mobilization of the AICA/PICA on the cerebellar surface in the surgical route. METHODS: Retrospective review of 101 patients dividing their cases into 2 groups, the mobilized group and nonmobilized group. Surgical results, brainstem auditory evoked potentials (BAEPs), age, and duration of microsurgery were compared. In the mobilized group, whether the artery was responsible for the HFS or not, and whether the artery branched perforators to the cerebellar surface or choroid plexus or not, were analyzed. RESULTS: No permanent hearing impairment occurred in any patient. The AICA/PICA was mobilized in 26 patients. No significant difference was found in surgical results, BAEP findings, and duration of microsurgery between the 2 groups, but age was younger in the mobilized group (P < .01). The mobilized artery was responsible in 14 cases and branched perforators in 7 cases in the mobilized group. The perforators did not obstruct mobilization. CONCLUSION: Mobilization of the AICA/PICA from the cerebellar surface is a useful technique to maintain the infrafloccular approach in MVD for HFS. This technique reduces the risk of postoperative hearing impairment. PMID- 29790979 TI - Petrosal Meningiomas: Factors Affecting Outcome and the Role of Intraoperative Multimodal Assistance to Microsurgery. AB - BACKGROUND: Petrous meningiomas (PMs) represent a subset of posterior fossa tumors accounting for ~8% of all intracranial meningiomas. Surgical treatment of PMs is challenging because of their relationships with vital neurovascular structures of the cerebellopontine angle. OBJECTIVE: To investigate independent pre- and intraoperative predictors of PM surgery outcome. METHODS: We reviewed the surgical and outcome data of patients who underwent microsurgical resection of PMs from 1997 to 2016. From 2007 onward, a multimodal intraoperative protocol consisting of intraoperative neuromonitoring (IONM), endoscopy, and indocyanine green (ICG) videoangiography was applied. Outcome variables included extent of resection, Karnofsky performance status (KPS), overall survival, and progression free survival (PFS). RESULTS: A total of 54 patients were included. Independent predictors of gross total resection (GTR) included retromeatal location (P < .0175; odds ratio [OR] 4.05), absence of brainstem compression (P < .02; OR 3.55), and histological WHO grade I (P < .001; OR 3.47). Nongiant size (P < .012; OR 4.38), and WHO grade I (P < .0001; OR 7.7) were independent predictors of stable or improved KPS. The use of multimodal intraoperative tools to assist surgery independently predicted GTR (P < .002; OR 6.8) and good KPS (P < .018; OR 4.23). Nongiant size (P = .01) and WHO grade I (P = .002) were significantly associated with increased PFS. CONCLUSION: Notwithstanding the limitations of a retrospective study, our results suggest that support of microsurgery by a combination of IONM, endoscopy, and ICG videoangiography may improve patient outcome in PM surgery. PMID- 29790981 TI - Economic Impact of Aging on the Initial Spine Care of Patients With Acute Spine Trauma: From Bedside to Teller. AB - BACKGROUND: Aging of the population has prompted an escalation of service utilization and costs in many jurisdictions including North America. However, relatively little is known on the economic impact of old age on the management of acute spine trauma (AST). OBJECTIVE: To examine the potential effects of age on the service utilization and costs of the management of patients with acute spine trauma. METHODS: This retrospective cohort study included consecutive patients with AST admitted to an acute spine care unit of a Canadian quaternary university hospital between February, 2002 and September, 2007. The study population was grouped into elderly (>=65 yr) and younger individuals. All costing data were converted and updated to US dollars in June/2017. RESULTS: There were 55 women and 91 men with AST (age range: 16-92 yr, mean age of 49.9 yr) of whom 37 were elderly. The mean total hospital costs for initial admission after AST in the elderly (USD $19 338 +/- $4892) were significantly greater than among younger individuals (USD $13 775 +/- $1344). However, elderly people had significantly lower per diem total, fixed, direct, and indirect costs for AST than younger individuals. Both groups were comparable regarding the proportion of services utilized in the acute care hospital. CONCLUSION: Given the escalating demand for surgical and nonsurgical spine treatment in the age of aging population, the timely results of this study underline key aspects of the economic impact of the spine care of the elderly. Further investigations are needed to fulfill significant knowledge gaps on the economics of caring for elderly with AST. PMID- 29790982 TI - Peritumoral Edema Relative to Meningioma Size Predicts Functional Outcomes after Resection in Older Patients. AB - BACKGROUND: Resection of meningiomas in older adults is associated with increased complications and postoperative functional deficits. Extent of peritumoral edema (PTE), which has been associated with surgical prognosis, may represent a preoperative risk marker for poorer outcomes in older adults. OBJECTIVE: To quantitatively evaluate the relationship between preoperative PTE and postresection outcomes in older meningioma patients. METHODS: One hundred twelve older meningioma patients (age >= 60) with evidence of PTE on MRI were reviewed. Extent of PTE, measured as a ratio of edema to tumor volume (edema index, EI) using semiautomatic image-processing software, was correlated with postresection outcomes. Other preoperative factors were included as covariates in multivariate analyses. Results were compared to matched nonedema older patients. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off EI values to predict postoperative outcomes. RESULTS: EI was associated with functional decline (as measured by Karnofsky Performance Status, KPS) at 6 mo, 1, 2 yr, and most recent follow-up (Ps < .05), but not among the nonedema matched patients. Seizure or prior stroke additionally trended towards increasing the likelihood of lower KPS at 2 yr (odds ratio = 3.06) and last follow-up (odds ratio = 5.55), respectively. ROC curve analysis found optimal cut-off values for EI ranging from 2.01 to 3.37 to predict lower KPS at each follow-up interval. Sensitivities ranged from 60% to 80%, specificities from 78% to 89%, and positive and negative predictive values from 38% to 58% and 80% to 97%. CONCLUSION: Preoperative PTE may represent a significant marker of poor functional outcome risk in older adults and provides a quantitative measurement to incorporate into surgical decision-making. PMID- 29790980 TI - Contrasting Patterns of Genomic Diversity Reveal Accelerated Genetic Drift but Reduced Directional Selection on X-Chromosome in Wild and Domestic Sheep Species. AB - Analyses of genomic diversity along the X chromosome and of its correlation with autosomal diversity can facilitate understanding of evolutionary forces in shaping sex-linked genomic architecture. Strong selective sweeps and accelerated genetic drift on the X-chromosome have been inferred in primates and other model species, but no such insight has yet been gained in domestic animals compared with their wild relatives. Here, we analyzed X-chromosome variability in a large ovine data set, including a BeadChip array for 943 ewes from the world's sheep populations and 110 whole genomes of wild and domestic sheep. Analyzing whole genome sequences, we observed a substantially reduced X-to-autosome diversity ratio (~0.6) compared with the value expected under a neutral model (0.75). In particular, one large X-linked segment (43.05-79.25 Mb) was found to show extremely low diversity, most likely due to a high density of coding genes, featuring highly conserved regions. In general, we observed higher nucleotide diversity on the autosomes, but a flat diversity gradient in X-linked segments, as a function of increasing distance from the nearest genes, leading to a decreased X: autosome (X/A) diversity ratio and contrasting to the positive correlation detected in primates and other model animals. Our evidence suggests that accelerated genetic drift but reduced directional selection on X chromosome, as well as sex-biased demographic events, explain low X-chromosome diversity in sheep species. The distinct patterns of X-linked and X/A diversity we observed between Middle Eastern and non-Middle Eastern sheep populations can be explained by multiple migrations, selection, and admixture during the domestic sheep's recent postdomestication demographic expansion, coupled with natural selection for adaptation to new environments. In addition, we identify important novel genes involved in abnormal behavioral phenotypes, metabolism, and immunity, under selection on the sheep X-chromosome. PMID- 29790984 TI - Co-translational protein targeting in bacteria. AB - About 30% of all bacterial proteins execute their function outside of the cytosol and have to be transported into or across the cytoplasmic membrane. Bacteria use multiple protein transport systems in parallel, but the majority of proteins engage two distinct targeting systems. One is the co-translational targeting by two universally conserved GTPases, the signal recognition particle (SRP) and its receptor FtsY, which deliver inner membrane proteins to either the SecYEG translocon or the YidC insertase for membrane insertion. The other targeting system depends on the ATPase SecA, which targets secretory proteins, i.e. periplasmic and outer membrane proteins, to SecYEG for their subsequent ATP dependent translocation. While SRP selects its substrates already very early during their synthesis, the recognition of secretory proteins by SecA is believed to occur primarily after translation termination, i.e. post-translationally. In this review we highlight recent progress on how SRP recognizes its substrates at the ribosome and how the fidelity of the targeting reaction to SecYEG is maintained. We furthermore discuss similarities and differences in the SRP dependent targeting to either SecYEG or YidC and summarize recent results that suggest that some membrane proteins are co-translationally targeted by SecA. PMID- 29790986 TI - Monitoring substrate enables real-time regulation of a protein localization pathway. AB - Protein localization machinery supports cell survival and physiology, suggesting the potential importance of its expression regulation. Here, we summarize a remarkable scheme of regulation, which allows real-time feedback regulation of the machinery expression. A class of regulatory nascent polypeptides, called monitoring substrates, undergoes force-sensitive translation arrest. The resulting ribosome stalling on the mRNA then affects mRNA folding to expose the ribosome-binding site of the downstream target gene and upregulate its translation. The target gene encodes a component of the localization machinery, whose physical action against the monitoring substrate leads to arrest cancellation. Thus, this scheme of feedback loop allows the cell to adjust the amount of the machinery to correlate inversely with the effectiveness of the process at a given moment. The system appears to have emerged late in evolution, in which a narrow range of organisms selected a distinct monitoring substrate machinery combination. Currently, regulatory systems of SecM-SecA, VemP-SecDF2 and MifM-YidC2 are known to occur in different bacterial species. PMID- 29790983 TI - Climate change and One Health. AB - The journal The Lancet recently published a countdown on health and climate change. Attention was focused solely on humans. However, animals, including wildlife, livestock and pets, may also be impacted by climate change. Complementary to the high relevance of awareness rising for protecting humans against climate change, here we present a One Health approach, which aims at the simultaneous protection of humans, animals and the environment from climate change impacts (climate change adaptation). We postulate that integrated approaches save human and animal lives and reduce costs when compared to public and animal health sectors working separately. A One Health approach to climate change adaptation may significantly contribute to food security with emphasis on animal source foods, extensive livestock systems, particularly ruminant livestock, environmental sanitation, and steps towards regional and global integrated syndromic surveillance and response systems. The cost of outbreaks of emerging vector-borne zoonotic pathogens may be much lower if they are detected early in the vector or in livestock rather than later in humans. Therefore, integrated community-based surveillance of zoonoses is a promising avenue to reduce health effects of climate change. PMID- 29790988 TI - Evaluation of a Music Therapy Social Skills Development Program for Youth with Limited Resources. AB - Background: Children living in low-resource communities are at risk for poorer socio-emotional development and academic performance. Emerging evidence supports use of group music therapy experiences to support social development through community afterschool programming. Objective: To examine the potential benefit of a music therapy social skills development program to improve social skills and academic performance of school-aged children with limited resources in an afterschool program. Method: We used a single-group pre/post-test design, and recruited 20 students (11 females, 9 males), ages 5 to 11 years, from an afterschool program. The music therapy social skills program consisted of eight 50-minute sessions, and we measured social competence and antisocial behavior using the Home & Community Social Behavioral Scale (HCSBS; Merrell & Caldarella, 2008), and social skills, problem behaviors, and academic competence using the Social Skills Improvement System (SSIS; Gresham & Elliot, 2008a, 2008b). Results: Only students who attended a minimum of six sessions (N = 14) were included in data analysis. Results showed no significant change in individual HBSC subscale scores; however, the total number of low-performance/high-risk skills significantly decreased. SSIS teacher results indicated significant improvement in communication, significant decrease of hyperactivity, autistic behavioral tendencies and overall problem behaviors, and marginal decreases in internalization. Parent ratings mirrored, in part, those of the teacher. Conclusions: Results indicated that music therapy has the potential of being an effective intervention for promoting social competence of school-aged children with limited resources, particularly in the areas of communication and low performance/high-risk behaviors. Teaching skills through song lyrics and improvisation emerged as salient interventions. PMID- 29790987 TI - Structural accommodations accompanying splicing of a group II intron RNP. AB - Group II introns, the putative progenitors of spliceosomal introns and retrotransposons, are ribozymes that are capable of self-splicing and DNA invasion. In the cell, group II introns form ribonucleoprotein (RNP) complexes with an intron-encoded protein, which is essential to folding, splicing and retromobility of the intron. To understand the structural accommodations underlying splicing, in preparation for retromobility, we probed the endogenously expressed Lactococcus lactis Ll.LtrB group II intron RNP using SHAPE. The results, which are consistent in vivo and in vitro, provide insights into the dynamics of the intron RNP as well as RNA-RNA and RNA-protein interactions. By comparing the excised intron RNP with mutant RNPs in the precursor state, confined SHAPE profile differences were observed, indicative of rearrangements at the active site as well as disengagement at the functional RNA-protein interface in transition between the two states. The exon-binding sequences in the intron RNA, which interact with the 5' exon and the target DNA, show increased flexibility after splicing. In contrast, stability of major tertiary and protein interactions maintains the scaffold of the RNA through the splicing transition, while the active site is realigned in preparation for retromobility. PMID- 29790985 TI - The way is the goal: how SecA transports proteins across the cytoplasmic membrane in bacteria. AB - In bacteria, translocation of most soluble secreted proteins (and outer membrane proteins in Gram-negative bacteria) across the cytoplasmic membrane by the Sec machinery is mediated by the essential ATPase SecA. At its core, this machinery consists of SecA and the integral membrane proteins SecYEG, which form a protein conducting channel in the membrane. Proteins are recognised by the Sec machinery by virtue of an internally encoded targeting signal, which usually takes the form of an N-terminal signal sequence. In addition, substrate proteins must be maintained in an unfolded conformation in the cytoplasm, prior to translocation, in order to be competent for translocation through SecYEG. Recognition of substrate proteins occurs via SecA-either through direct recognition by SecA or through secondary recognition by a molecular chaperone that delivers proteins to SecA. Substrate proteins are then screened for the presence of a functional signal sequence by SecYEG. Proteins with functional signal sequences are translocated across the membrane in an ATP-dependent fashion. The current research investigating each of these steps is reviewed here. PMID- 29790990 TI - Women's mental health in the perinatal period according to migrant status: the French representative ELFE birth cohort. AB - Background: Mental health problems in the perinatal period are common. We examined associations between different categories of migrant status and region of origin in relation to mental health during pregnancy and at 2 months post partum. Methods: We analyzed data from the French nationally representative Etude Longitudinale Francaise depuis l'Enfance birth cohort (n = 17 988). Migrant status was divided into five categories: 'majority population', 'descendants with one migrant parent', 'descendants with two migrant parents', 'naturalized migrant' and 'non-naturalized migrant women'. Multivariate logistic regression models were implemented to examine associations between migrant status and mental health outcomes: persistent psychological difficulties during pregnancy as well as mother's depression and poor self-reported health at 2 months post-partum. Results: After adjusting for covariates, migrant status was not associated with psychological difficulties during pregnancy. Descendants of migrants had comparable mental health to the majority population. Non-naturalized migrant women were more likely to experience depression (odd's ratio (OR)= 1.66, 95%confidence interval (CI): 1.27, 2.20) and poor self-reported health (OR = 1.45, 95%CI: 1.06, 1.98) during the post-partum period. The region of origin was associated with post-partum health independently of migrant status, such that women from Africa and Turkey were most likely to have depression or poor self rated health. Conclusion: First, but not second, generation migrant women appear to have high levels of mental health difficulties during the post-partum period. Women from North Africa, Sub-Saharan Africa, and Turkey have higher levels of distress than those from other regions. In particular, non-naturalized migrant appear to be a vulnerable group; they may disproportionately face stressors that increase their risk for post-partum depressive symptoms. PMID- 29790989 TI - The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. AB - Galaxy (homepage: https://galaxyproject.org, main public server: https://usegalaxy.org) is a web-based scientific analysis platform used by tens of thousands of scientists across the world to analyze large biomedical datasets such as those found in genomics, proteomics, metabolomics and imaging. Started in 2005, Galaxy continues to focus on three key challenges of data-driven biomedical science: making analyses accessible to all researchers, ensuring analyses are completely reproducible, and making it simple to communicate analyses so that they can be reused and extended. During the last two years, the Galaxy team and the open-source community around Galaxy have made substantial improvements to Galaxy's core framework, user interface, tools, and training materials. Framework and user interface improvements now enable Galaxy to be used for analyzing tens of thousands of datasets, and >5500 tools are now available from the Galaxy ToolShed. The Galaxy community has led an effort to create numerous high-quality tutorials focused on common types of genomic analyses. The Galaxy developer and user communities continue to grow and be integral to Galaxy's development. The number of Galaxy public servers, developers contributing to the Galaxy framework and its tools, and users of the main Galaxy server have all increased substantially. PMID- 29790991 TI - Understanding delays in acute stroke care: a systematic review of reviews. AB - Background: Stroke is the leading cause of adult long-term disability in Western countries. Intravenous thrombolytic therapy with recombinant tissue plasminogen activator is safe and effective within the first 4.5 h after the onset of stroke. Various factors delaying acute stroke care have been identified in the literature. This review aimed to provide an overview of factors delaying acute stroke care and attempted to show how they interact in a synthetic framework. Methods: We conducted a systematic review of literature reviews published in Medline and DORIS until 2016 on factors influencing acute stroke pathway timeframe. Results: We analyzed 31 reviews that cover all factors of delays from stroke onset to treatment. We identified 27 factors that had a significant impact on acute stroke care and can be categorized into four distinct categories: patient-related factors, training, resources and lack of coordination. We also reported associations between factors observed in both between categories (mainly between patients and organizational/logistical factors) and within categories. Conclusion: This review provides a wide overview of factors influencing acute stroke pathway. Since it was observed that the identified factors were interrelated, they needed to be analyzed in a systematic way. We hence created a synthetic framework that combines several categories of factors while assuming that factor weight varies from a study context to another. Better knowledge on underlying mechanisms between factors would provide crucial improvement of the interventions aiming at reducing delays in both pre-hospital and inhospital stages. For future research, we recommend adopting a systemic perspective on factors influencing acute stroke pathway. PMID- 29790992 TI - Investing in public health-driving prosperity for the present and future generations. PMID- 29790993 TI - Sleep pirates-are we really living through a sleep deprivation epidemic and what's stealing our sleep? PMID- 29790995 TI - Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer. AB - This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6-12 months, (ii) 12-24 months, (iii) 24-36 months, (iv) 36-48 months and (v) 48-60 months after PBT. Late (>=6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383-8.). CT scans of 113 patients (median follow-up, 36 months; range, 24-137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6-62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12-21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes. PMID- 29790996 TI - DNA methylation and inflammation marker profiles associated with a history of depression. AB - Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified six significant (Sidak corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidak corrected P = 1.27 * 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL 6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype. PMID- 29790998 TI - Association of Smokeless Tobacco Use and Oral Cancer: A Systematic Global Review and Meta-Analysis. AB - Introduction: Smokeless tobacco products have been linked to precancerous and cancers of oral cavity for long. Evidence was available on the association between smokeless tobacco (SLT) products and oral cancers at regional but not at global level. Present meta-analysis is aimed to evaluate the risk of oral cancer with the use of SLT products among "ever" versus "never" users. Method: Studies published for the period (1960-2016) are retrieved using Pubmed, Indmed, EMBASE, and Google Scholar search engines for the subject "ever" versus "never" users of SLT products and estimated the risk association with oral cancer. Summary odds ratios (relative risk) are estimated and meta-analysis was performed using random effects model. Results: Thirty-seven studies from four of six WHO regions, Southeast Asia region (SEAR), the Eastern Mediterranean Region (EMR), Europe, and region of Americas (North and South) are included in the analysis. Significant risk with SLT products with oral cancer was found for SEAR (4.44, 95% CI = 3.51 to 5.61) and for EMR (1.28, 95% CI = 1.04 to 1.56). Significantly higher risk (p < .001) was found for females (5.83, 95% CI = 2.93 to 11.58). Product wise analysis for different SLT products revealed various levels of risk viz. gutkha (8.67, 95% CI = 3.59 to 20.93), pan tobacco / betel liquid (7.18, 95% CI = 5.48 to 9.41), oral snuff (4.18, 50% CI = 2.37 to 7.38), Mainpuri tobacco (3.32, 95% CI = 1.32 to 8.36), and snus (0.86, 95% CI = 0.58 to 1.29). Conclusion: A significant positive association was observed between SLT use and the risk of oral cancer, in SEAR, EMRs, and among women users. Implications: The present meta analysis demonstrates SLT product use and the risk of oral cancer at global level. Moreover, the present analysis provided data on the risk associated with individual SLT product. The results fulfil the gap in the data on independent effect of individual SLT product use on the outcome of oral cancer at global level, conclusively. Chewing SLT products was associated with higher risk of oral cancer than other types of SLT. This can serve as a useful tool for policy makers in forming strict policies in controlling SLT menace. Hence, we propose that in addition to smoking, efforts should be directed towards SLT product cessation as well in reducing oral cancer incidence. PMID- 29790997 TI - A multi-institutional study of independent calculation verification in inhomogeneous media using a simple and effective method of heterogeneity correction integrated with the Clarkson method. AB - In inhomogeneous media, there is often a large systematic difference in the dose between the conventional Clarkson algorithm (C-Clarkson) for independent calculation verification and the superposition-based algorithms of treatment planning systems (TPSs). These treatment site-dependent differences increase the complexity of the radiotherapy planning secondary check. We developed a simple and effective method of heterogeneity correction integrated with the Clarkson algorithm (L-Clarkson) to account for the effects of heterogeneity in the lateral dimension, and performed a multi-institutional study to evaluate the effectiveness of the method. In the method, a 2D image reconstructed from computed tomography (CT) images is divided according to lines extending from the reference point to the edge of the multileaf collimator (MLC) or jaw collimator for each pie sector, and the radiological path length (RPL) of each line is calculated on the 2D image to obtain a tissue maximum ratio and phantom scatter factor, allowing the dose to be calculated. A total of 261 plans (1237 beams) for conventional breast and lung treatments and lung stereotactic body radiotherapy were collected from four institutions. Disagreements in dose between the on-site TPSs and a verification program using the C-Clarkson and L-Clarkson algorithms were compared. Systematic differences with the L-Clarkson method were within 1% for all sites, while the C-Clarkson method resulted in systematic differences of 1-5%. The L-Clarkson method showed smaller variations. This heterogeneity correction integrated with the Clarkson algorithm would provide a simple evaluation within the range of -5% to +5% for a radiotherapy plan secondary check. PMID- 29790999 TI - Editorial: Reflections on Bioethics and Law: Yesterday, Today and Tomorrow. PMID- 29791000 TI - Gross Negligence (Medical) Manslaughter and the Puzzling Implications of Negligent Ignorance: Rose v R [2017] EWCA Crim 1168. AB - This commentary explores the Court of Appeal's decision in the case of Rose1 in order to assess the risk of liability for gross negligence manslaughter currently faced by the medical profession in the event that negligence causes the death of a patient. Subtly modifying the test established in Adomako,2Rose confirms that in order to be potentially liable, there must be a serious risk of death that was, rather than ought to have been, obvious/foreseeable to the defendant. Consequently, in more complex cases where the serious risk of death is not immediately obvious, negligently failing to assess risk seems to prevent potential liability on the basis that the putative defendant was in a position of negligent ignorance. PMID- 29791001 TI - Plain language emergency alert codes: The importance of direct impact statements in hospital emergency alerts. AB - The nature of an emergency is not predictable, and no two emergencies are alike. In response to this unpredictable nature, healthcare facilities across the nation have adopted a system of emergency codes to notify staff of an emergent situation, often without alerting patients and visitors to the crises. However, the system of emergency codes varies significantly within most states and even within healthcare coalition regions. This variation in codes leads to not only the potential for staff confusion, considering many healthcare providers work within multiple healthcare centers, but also decreases the amount of transparency a healthcare center projects to its patients and visitors. The research conducted as part of this study indicated that an overwhelming majority of healthcare professionals would prefer voluntary plain language emergency code standardization to the current individual code systems. PMID- 29791002 TI - Optimizing stadium evacuation by integrating geocomputation and affordance theory. AB - Football is culturally and economically important in the United States, and football stadiums are part of the country's critical infrastructure, thus receiving government protection against hazard events. In this project, an agent based evacuation model was implemented to optimize evacuation time from The University of Southern Mississippi's M.M. Roberts Stadium (football) by accounting for evacuees' age, gender, physical fitness, alcohol consumption, and prior experience with hazard events. The findings revealed that (i) the age and gender of an individual impact his/her locomotion speed and (ii) evacuation route choice is influenced by evacuees' perception of its safety and effectiveness. The estimated evacuation times for all evacuees to exit only the stadium and the stadium plus the surrounding campus were 20.82 and 165.01 minutes, respectively. Both of these times were shorter than the evacuation times determined by models employing location-unspecific locomotion speeds. One-way analysis of variance revealed that there were statistically significant differences between use of location-specific and location-unspecific within-stadium evacuation times (p <= 0.001 with alpha = 0.05). These results suggest that using local data is vital to accurately estimate evacuation time. PMID- 29791003 TI - Evacuate or shelter in place: A view from the water's edge. AB - Hospitals are faced with the difficult decision as whether to evacuate their patients or shelter in place when a strong hurricane is predicted to affect the facility. This decision must balance for patients the risk of transport with the risk of staying. This article discusses the experience of a hospital faced with this problem in two consecutive years. The approach taken differed and the evaluation of the implications are discussed. PMID- 29791004 TI - Stories after disaster survival: Preparing, heeding warnings, and self-reliance. AB - OBJECTIVE: The purpose of the study was to examine the content of stories told by people personally impacted by disasters. DESIGN: Semistructured, qualitative interviews. SETTING: Northwest part of a mid-south state. PARTICIPANTS: Fourteen disaster survivors who were recruited through their attendance at an emergency preparedness-related fair. MAIN OUTCOME MEASURES: Interview schedule based on previous research using the family resilience framework. RESULTS: Three themes emerged: prior emergency preparation, heeding warnings of impending disaster, and rural self-reliance. CONCLUSIONS: Participants had made prior emergency preparedness plans, but their personal experiences led to them adjusting their plans, or making more relevant plans for future disasters. Participants expressed the importance of sharing their experiences with family and community members, expressing hope that others would learn, vicariously rather than first-hand, from their experiences. PMID- 29791005 TI - No one left behind: Postevent experiences of differently abled individuals in Denmark. AB - PURPOSE: This descriptive study explored barriers and difficulties faced by individuals with a physical disability (IPD) in Denmark in situations of disaster and in everyday problems. METHODS: Semistructured interviews were conducted with 12 IPD who had experienced a possible traumatic event. Due to a lack of participants who experienced a traumatic event, the authors expanded their recruitment strategy to include IPD, who had experienced other critical situations (eg, accidents and personal crises). RESULTS: Difficulties centered on four major themes: (1) lack of guidelines and evacuation plans, (2) differences in reaction to crisis, (3) a lack of empathy and special care from professionals and a general lack of communication directly to the IPD, and (4) great inequality in the municipals and no consistent rules for what a IPD is entitled to. CONCLUSIONS: This study has identified significant gaps in predisaster and postdisaster service provision for IPD. There is a need for general evacuation guidelines and more specialized professional help to provide better aftercare according to the different needs of the IPD. The results of this study can inform policy makers to enhance existing services and/or develop new guidelines and evacuation plans targeted at this population. PMID- 29791006 TI - Examining the influence of professional emergency management coordinators driving preparedness and resilience on university campuses. AB - OBJECTIVE: To characterize the compliance with disaster management recommendations of ensuring a full-time, dedicated professional is responsible for coordinating disaster management programs. This research targets a subset of institutions of higher education (IHEs) in the United States at risk of annual hurricane threats or having experienced an active shooter incident near campus. DESIGN: A comprehensive Web-based assessment was conducted to determine the Web presence of emergency management of 265 IHEs with student enrollment greater than 2,000 in coastal states at risk of annual Atlantic Hurricane landfalls. Results were displayed spatially using ArcGIS. RESULTS: Although the Web sites of 91 percent of IHEs with enrollment greater than 20,000 displayed easily accessible information on a dedicated professional leading emergency management, only 42 percent of the Web sites of those IHEs with enrollment between 10,000 and 20,000 did so. As enrollment declined, the compliance rate declined. Compliance rates for IHEs with different enrollments were as follows: 6,001-9,999, 30 percent; 3,001-6,000, 23 percent; 2,000-3,000, 13 percent. CONCLUSIONS: A full-time, dedicated professional coordinating emergency preparedness is a best practice as evidenced by various accrediting bodies, but this practice is not mandated for IHEs. Our results suggest that proximity to significant annual hurricane threats does not influence the adoption of this recommendation. Despite IHEs being core stakeholders in assuring disaster resilience, gaps exist in preparedness practice. PMID- 29791007 TI - Should all patients with adrenal insufficiency or a subgroup of patients with prediabetes be treated with dual-release hydrocortisone? PMID- 29791008 TI - The Pharmacology, Pharmacokinetics, Efficacy, and Adverse Events Associated With Kava. AB - Kava is a plant with numerous kavapyrones that can induce pharmacologic effects and drug interactions through the cytochrome P450 and P-glycoprotein systems. Kava is used recreationally and for the treatment of anxiety. Clinical trials verify anxiolytic effects in excess of placebo, but the effects are not seen immediately and the optimal dose and dosing schedule needs to be determined. Clinical trials usually lasting for 4 weeks found generally good tolerability and safety; however, dermatologic, hepatologic, and cognitive adverse effects may occur. Some of these adverse effects are known to occur from the kavapyrones themselves, while others can be caused or exacerbated by use of substandard kava products. There is tremendous variability in the constitution of a kava product based on the parts of the plant that are being extracted and the extraction method. The most commonly studied extract for the treatment of anxiety is the acetone extract. PMID- 29791009 TI - WITHDRAWN: Interventions for replacing missing teeth: 1- versus 2-stage implant placement. AB - BACKGROUND: Implants may be placed penetrating the oral mucosa (1-stage procedure) or can be completely buried under the oral mucosa (2-stage procedure) during the healing phase of the bone at the implant surface. With a 2-stage procedure the risk of having unwanted loading onto the implants is minimized, but a second minor surgical intervention is needed to connect the healing abutments and more time is needed prior to start the prosthetic phase because of the wound healing period required in relation to the second surgical intervention. OBJECTIVES: To evaluate whether a 1-stage implant placement procedure is as effective as a 2-stage procedure. SEARCH METHODS: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched. Handsearching included several dental journals. Authors of all identified trials, an Internet discussion group and 55 dental implant manufacturers were contacted to find unpublished randomised controlled trials (RCTs). The last electronic search was conducted on 21 January 2009. SELECTION CRITERIA: All RCTs of osseointegrated dental implants comparing the same dental implants placed according to 1- versus 2-stage procedures with a minimum follow up of 6 months after loading. Outcome measures were: prosthesis failures, implant failures, marginal bone level changes on intraoral radiographs, patient preference including aesthetics, aesthetics evaluated by dentists, and complications. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Authors were contacted for missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. MAIN RESULTS: Five RCTs were identified and included reporting data on 239 patients in total. On a patient, rather than per implant basis, the meta-analyses showed no statistically significant differences for prosthesis and implant failures, though trends, especially in fully edentulous patients, favoured 2-stage (submerged) implants. AUTHORS' CONCLUSIONS: The number of patients included in the trials was too small to draw definitive conclusions. The 1-stage approach might be preferable in partially edentulous patients since it avoids one surgical intervention and shortens treatment times, while a 2-stage submerged approach could be indicated when an implant has not obtained an optimal primary stability or when barriers are used for guided tissue regeneration, or when it is expected that removable temporary prostheses could transmit excessive forces on the penetrating abutments especially in fully edentulous patients. PMID- 29791010 TI - New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis. AB - BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care. PMID- 29791011 TI - A Pharmacokinetic and Pharmacogenetic Analysis of Osteosarcoma Patients Treated With High-Dose Methotrexate: Data From the OS2006/Sarcoma-09 Trial. AB - Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials.gov. Identifier: NCT00470223). PK data were analyzed using the nonlinear mixed-effect modeling software program Monolix. The influence of each SNP was evaluated using a stepwise procedure under additive, recessive, or dominant genetic model. The likelihood ratio test was used to test the effect of each SNP on PK parameters. Overall, 187 patients with 7898 MTX blood concentrations were included in the PK-pharmacogenetic analysis. A 2-compartment model adequately described the data. Although high-dose MTX dosing recommendations in pediatric patients are currently based on body surface area, body weight was more predictive of clearance between-subject variability than body surface area. The most significant polymorphism associated with MTX clearance was rs13120400 (on the ABCG2 gene) under the recessive genetic model (P < .0001). GG genotype carriers for rs13120400 appeared to have a moderate decrease in MTX exposure compared to AA or GA carriers. PMID- 29791012 TI - A systematic mixed studies review of women's experiences of perineal trauma sustained during childbirth. AB - AIM: To explore the quantitative/qualitative literature on women's experiences of perineal trauma sustained during childbirth and the impact it may have on psychological/emotional wellbeing BACKGROUND: Obstetric complications during childbirth can be a risk factor for postpartum psychological distress. Perineal trauma is one of the most frequent obstetric complications and it is important to understand any impact on psychological/emotional wellbeing. DESIGN: A convergent qualitative design using a hybrid deductive-inductive thematic synthesis approach to data transformation was used. DATA SOURCES: Web of knowledge, CINAHL, MEDLINE, AMED, PsyArticles, PsycInfo until May 2017. REVIEW METHODS: Stage 1: transforming findings from the qualitative, quantitative and mixed methods studies into themes using thematic synthesis. Stage 2: integrating themes from the quantitative studies into those derived from the qualitative studies RESULTS: Records (N=2152) found of which 11 qualitative 22 quantitative and 1 mixed methods were included in this review. Five themes were derived from thematic synthesis of qualitative studies 'The mystery of perineal trauma', 'The misery of perineal suturing', 'The postnatal perineum', 'Normalisation and feeling dismissed' and 'Adjusting to a new normal - Coping and compromise' and five themes identified from the quantitative studies, experience of birth (N=4), Sexual functioning (N=12), Social functioning (N=2), Psychological health (N=8) and Quality of Life (N=5). CONCLUSION: Perineal trauma can have a negative impact on psychological/emotional wellbeing, however the literature is conflicted and in need of clarification. Future research should clearly describe the perineal status of the women in the sample, use validated measures and consider the timing of such measures. This article is protected by copyright. All rights reserved. PMID- 29791015 TI - Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis. PMID- 29791016 TI - Clarification-safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis. PMID- 29791013 TI - Frontline Science: Buprenorphine decreases CCL2-mediated migration of CD14+ CD16+ monocytes. AB - HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14+ CD16+ monocytes are a mature subpopulation that is increased in number in the peripheral blood of HIV-infected people. Mature monocytes can be productively infected with HIV, and they transmigrate preferentially across the BBB in response to CCL2, a chemokine elevated in the CNS and CSF of HIV-infected people even with ART. Buprenorphine, an opioid derivate, is an opioid replacement therapy for heroin addiction. It is a partial agonist of MU-opioid receptor and full antagonist of kappa-opioid receptor. The effects of buprenorphine on CCL2 mediated CD14+ CD16+ monocytes transmigration across the BBB, a critical mechanism that promotes neuroinflammation and HAND, have not been characterized. We showed for the first time that buprenorphine decreases several steps of CCL2 mediated human mature monocyte transmigration. We propose that buprenorphine treatment in the context of HIV infection could serve a dual purpose, to treat opioid addiction and also to reduce neuroinflammation. Additionally, buprenorphine may be used as a treatment for HAND not only in the context of opioid abuse. PMID- 29791014 TI - Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady-state disposition of lamotrigine in adults with epilepsy. AB - AIMS: To investigate the impact of glucuronidation enzyme (UGT1A4*3 142T>G, UGT1A4*2 70C>A, UGT2B7 -161C>T) and transporter (MDR1/ABCB1 1236C>T, ABCG2 421C>A) polymorphisms on steady-state disposition of lamotrigine and on the lamotrigine-valproate interaction. METHODS: Adults with epilepsy on lamotrigine monotherapy (n = 131) or lamotrigine + valproate treatment (n = 74) were genotyped and steady-state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring. RESULTS: No effect of UGT and MDR1/ABCB1 polymorphisms was observed. In the entire cohort, ABCG2 421A allele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine-only patients, variant allele (vs. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR) = 0.76, 95% confidence interval (CI) 0.59-0.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR = 1.72, 95%CI 1.14-2.62); (ii) valproate cotreatment was overall associated with markedly higher troughs vs. lamotrigine monotherapy (GMR = 3.49, 95%CI 2.73-4.44), but more so in variant allele carriers (GMR = 5.24, 95%CI 3.38-8.15) than in wild type homozygotes (GMR = 2.32, 95%CI 1.89-2.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36-fold (95%CI 1.39-3.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs. CONCLUSION: This study is first to indicate a potentially relevant interaction between ABCG2 421C>A polymorphism and valproate in their effects on lamotrigine disposition. PMID- 29791017 TI - Addressing the vexed issue of authorship and author order: A discussion paper. AB - AIMS: To review and discuss authorship and author order in the context of nursing and midwifery publications and to present a set of principles to guide and justify author order. BACKGROUND: Variation in author order trends is evident across different authors, disciplines and countries. Confusion and conflict between authors give rise to important issues concerning ethics and collaboration and may delay publication. Lack of transparency in authorship practices also impedes judgements when individual contributions are used in support of employment, promotion, tenure and/or research funding applications. DESIGN: Discussion paper. DATA SOURCES: A literature search of BioMed Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE with Full Text and PubMed for original peer-reviewed papers published in English between 2007 - 2017, in the disciplines of nursing and midwifery. IMPLICATIONS FOR NURSING: Much is written about authorship practices across disciplines and countries. Despite existing authorship guidelines, author order remains an area of confusion and contention. Disputes about authorship and author order have the potential to cause distrust and breakdowns in research relationships, thereby disrupting nursing and midwifery scholarship and research. The main issues concern honorary and ghost authorship, authorship versus acknowledgement, confusion about collaboration, author order, research students as co-authors, equal author credit and the need for explicit guidelines. CONCLUSION: Good communication and mutual respect are crucial to the authorship process. However, clear instructions are needed to guide decisions on authorship and author order. It is recommended that the "first-last-author-emphasis" be adopted uniformly internationally across nursing and midwifery research. PMID- 29791018 TI - A rare case of a solitary fibrous tumour of bone showing NAB2-STAT6 exon 3-exon 19 fusion. PMID- 29791019 TI - WITHDRAWN: Treatments for adults with prominent lower front teeth. AB - BACKGROUND: Prominent lower front teeth may be associated with a large or prognathic lower jaw (mandible) or a small or retrusive upper jaw (maxilla). Edward Angle, who may be considered the father of modern orthodontics, classified the malocclusion in this situation as Class III. The individual is described as having a negative or reverse overjet as the lower front teeth are more prominent than the upper front teeth. OBJECTIVES: The purpose of this systematic review was to evaluate different treatments of Angle Class III malocclusion in adults. SEARCH METHODS: The following databases were searched: Cochrane Oral Health Group Trials Register (to 22 March 2012); CENTRAL (The Cochrane Library 2012, Issue 1); MEDLINE via OVID (1950 to 22 March 2012); EMBASE via OVID (1980 to 22 March 2012); LILACs (1982 to 22 March 2012); BBO (1986 to 22 March 2012); and SciELO (1997 to 22 March 2012). SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of treatments for adults with an Angle Class III malocclusion were included. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility of the identified reports. Two review authors independently extracted data and assessed the risk of bias in the included studies. The mean differences with 95% confidence intervals were calculated for continuous data. MAIN RESULTS: Two randomized controlled trials were included in this review. There are different types of surgery for this type of malocclusion but only trials of mandible reduction surgery were identified. One trial compared intraoral vertical ramus osteotomy (IVRO) with sagittal split ramus osteotomy (SSRO) and the other trial compared vertical ramus osteotomy (VRO) with and without osteosynthesis. Neither trial found any difference between the two treatments. The trials did not provide adequate data for assessing effectiveness of the techniques described. AUTHORS' CONCLUSIONS: There is insufficient evidence from the two included trials, to conclude that one procedure is better or worse than another. The included trials compared different interventions and were at high risk of bias and therefore no implications for practice can be given. Further high quality randomized controlled trials with long term follow-up are required. PMID- 29791020 TI - Discursive constructions of professional identity in policy and regulatory discourse. AB - AIM: To examine and describe disciplinary discourses conducted through professional policy and regulatory documents in nursing and midwifery in Ireland. BACKGROUND: A key tenet of discourse theory is that group identities are constructed in public discourses and these discursively constructed identities become social realities. Professional identities can be extracted from both the explicit and latent content of discourse. Studies of nursing's disciplinary discourse have drawn attention to a dominant discourse that confers nursing with particular identities, which privilege the relational and affective aspects of nursing and, in the process, marginalize scientific knowledge and the technical and body work of nursing. DESIGN: We used critical discourse analysis to analyse a purposive sample of nursing and midwifery regulatory and policy documents. METHOD: We applied a four-part, sequential approach to analyse the selected texts. This involved identifying key words, phrases and statements that indicated dominant discourses that, in turn, revealed latent beliefs and assumptions. The focus of our analysis was on how the discourses construct professional identities. FINDINGS: Our analysis indicated recurring narratives that appeared to confer nurses and midwives with three dominant identities: "the knowledgeable practitioner," the "interpersonal practitioner" and the "accountable practitioner." The discourse also carried assumptions about the form and content of disciplinary knowledge. CONCLUSIONS: Academic study of identity construction in discourse is important to disciplinary development by raising nurses' and midwives' consciousness, alerting them to the ways that their own discourse can shape their identities, influence public and political opinion and, in the process, shape public policy on their professions. PMID- 29791022 TI - The Very Little Lady...Who Wasn't So Little: Steve Olshansky,* "The Otter". PMID- 29791021 TI - ImmTAC/Anti-PD-1 antibody combination to enhance killing of cancer cells by reversing regulatory T-cell-mediated immunosuppression. AB - Recently, bi-functional molecules that can redirect immune effectors to tumour cells have emerged as potentially robust mediators of tumour regression in clinical trials. Two modalities in particular, bi-specific antibodies for T-cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC), are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy. In light of this, we evaluated the impact of induced regulatory T (iTreg) cells on the efficacy of tumour cell killing redirected by ImmTAC and demonstrated down-regulation of T cell proliferation and expression of CD25, CD107a, Granzyme B and Perforin by ImmTAC-redirected T cells. Significant recovery of ImmTAC potency, however, could be achieved when combined with an anti-programmed cell death protein 1 monoclonal antibody. Furthermore, we found that among lung cancer patients failing to respond to ImmTAC therapy, there was a significantly higher fraction of Treg cells in the peripheral blood mononuclear cells of lung cancer patients than in healthy donors. These results provide in vitro evidence for an iTreg cell mediated immunosuppression of ImmTAC-redirected T-cell responses. Whilst immune checkpoint blockade can reverse the Treg cell suppression, it forms a rational basis for a combination of the blockade with ImmTAC in clinical trials. PMID- 29791024 TI - Implantable cardioverter-defibrillator bridging from temporariness to permanence. PMID- 29791023 TI - Comparison of the Cockcroft-Gault, MDRD and CKD-EPI equations for estimating ganciclovir clearance. AB - AIMS: Accurately estimating kidney function is essential for the safe administration of renally cleared drugs such as ganciclovir. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault equation. There are no data on the utility of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in ganciclovir dosing. To evaluate which renal function equation best predicts ganciclovir clearance. METHODS: The performance of the Cockcroft-Gault equation, isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD study (MDRD4-IDMS) equation and CKD-EPI equation in determining ganciclovir clearance were assessed retrospectively in patients treated with ganciclovir from 2004-2015. The MDRD4-IDMS and CKD-EPI equations adjusted to individual body surface area (MDRD4-IDMS.BSA and CKD-EPI.BSA, respectively) were also evaluated. Patients with intravenous ganciclovir peak and trough concentrations in their medical records were included in the study. Ganciclovir clearance was calculated from serum concentrations using a one-compartment model. The five equations were compared based on their predictive ability, the coefficient of determination, through a linear regression analysis. The results were validated in a group of patients. RESULTS: One hundred patients were included in the final analysis. Seventy-four patients were analysed in the learning group and 26 in the validation group. The coefficient of determination was 0.281 for Cockcroft-Gault, 0.301 for CKD-EPI.BSA, 0.308 for MDRD4-IDMS.BSA, 0.324 for MDRD4-IDMS and 0.360 for CKD-EPI. Subgroup analysis also showed that CKD-EPI is a better predictor of ganciclovir clearance. Analysis of the validation group confirmed these results. CONCLUSIONS: The CKD-EPI equation correlates better with ganciclovir clearance than the Cockcroft-Gault and MDRD4-IDMS equations, even the clinical difference between the equations is scarce. PMID- 29791025 TI - Factors associated with quality of life of dementia caregivers: Direct and indirect effects. AB - AIMS: To examine the direct and indirect relationships between the characteristics of people with dementia and caregivers associated with caregivers' quality of life. BACKGROUND: Complex relationships exist among the factors associated with caregivers' quality of life. DESIGN: This study was a retrospective cross-sectional design. METHODS: The data were retrospectively extracted from participants who had visited the Center for Diagnosis of Dementia at Kyoto Prefectural University of Medicine from April 2013-March 2016. The data search was conducted on 21 April 2017. In total, 110 people with dementia and their caregivers participated. The characteristics of people with dementia were evaluated in terms of cognitive function, basic and instrumental activities of daily living and neuropsychiatric symptoms. We also evaluated caregivers' quality of life, depressive symptoms and care burden. Path analysis was used to investigate direct and indirect relationships. RESULTS: The path analysis revealed that care burden and depressive symptoms directly affected caregivers' quality of life. Furthermore, declines in instrumental activities of daily living among people with dementia indirectly affected caregivers' quality of life, while declines in cognitive function of people with dementia also indirectly affected caregivers' care burden and depressive symptoms. CONCLUSION: Caregiver quality of life was directly and indirectly affected by the characteristics of caregivers and people with dementia. The present findings provided evidence that factors related to both people with dementia and caregivers should be considered when nursing interventions are conducted. PMID- 29791026 TI - CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation. AB - Leukocyte entry into the CNS is a crucial step in the development of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Adhesion molecules mediating the docking of leukocytes to the endothelium of the blood-brain barrier (BBB) represent valuable targets for interference with the disease. However, little is known about the adhesion and signaling mechanisms in endothelial cells that mediate the diapedesis through the BBB. Here, we show that conditional Tie-2-Cre driven gene inactivation of CD99L2 inhibits leukocyte entry into the CNS during active MOG35-55 -induced EAE and alleviates severity of the disease. No detrimental effect on the immune response was observed. The number of perivascular cuffs around vessels of the CNS was reduced, as was the number of inflammatory foci, sites of demyelination and expression levels of pro inflammatory cytokines. Three-dimensional analysis of vibratome sections of the CNS revealed an accumulation of leukocytes between endothelial cells and the underlying basement membrane, whereas leukocyte docking to the luminal surface of the endothelium of the BBB was unaffected. Collectively, these results suggest that CD99L2 participates in the development of EAE by supporting diapedesis of leukocytes through the endothelial basement membrane of blood vessels of the BBB in the CNS. PMID- 29791027 TI - Phenotypic and molecular changes in nodule-in-nodule hepatocellular carcinoma with pathogenetic implications. AB - AIMS: Nodule-in-nodule (N/N) hepatocellular carcinoma (HCC) is a convincing proof of multistep hepatocarcinogenesis. In this lesion, an inner HCC develops within an outer, more differentiated, tumour, which can be rapidly taken over by the former so that N/N HCC is rarely detected. METHODS AND RESULTS: Ten resected N/N HCCs arising in cirrhotic background and characterized: (i) as outer lesions by early (n = 3) and G1 (n = 7) HCC; (ii) as inner lesions by G1 (n = 3) and G2 (n = 7) HCC. The largest/smallest diameters of outer and inner nodules were, respectively, 20/6 mm and 16/4 mm. We investigated vascular (CD34 and endocan), hepatocellular VEGF, GS, GPC3, HSP70 and CHC) and molecular (TERT promoter and beta-catenin) changes taking place from the outer neoplastic compartment to the inner neoplastic compartment (INC). A diffuse pattern of CD34+ capillarized vessels and focal endocan immunoreactivity were major distinctive features acquired in the INC; VEGF immunoreactivity was inversely related to CD34 staining. A gain in the number of cells immunoreactive for GPC3, HSP70, and CHC, but not of GS-immunoreactive cells, also occurred in the INC. TERT promoter mutations were seen in half of the cases in both compartments, whereas beta catenin mutations were more rarely detectable. CONCLUSIONS: Major phenotypic changes take place in the INC of N/N HCC. TERT promoter mutations take place frequently and very early, and, in contrast to beta-catenin mutations, do not appear to be acquired during N/N growth. These findings suggest that inner nodules represent a step further along the pathway of tumour progression, in contrast to earlier, simply initiated, lesions, and that complete neovascularisation predicts a change in HCC biology. PMID- 29791028 TI - Response to letter "Implantable cardioverter-defibrillator bridging from temporariness to permanence". PMID- 29791029 TI - Development of a 3D ultrasound guidance system for permanent breast seed implantation. AB - PURPOSE: Permanent breast seed implantation (PBSI) is a promising radiotherapy technique for early-stage breast cancer, completed in a single visit by permanently implanting 103 Pd seeds using needles inserted through a template and guided by two-dimensional (2D) ultrasound (US). However, operator dependence has been highlighted as a limitation of this procedure. Consequently, we propose and have developed an intraoperative guidance system using three-dimensional (3D) US and an instrumented mechanical arm to provide intraoperative 3D imaging and needle template tracking. METHODS: A mechatronic 3D US scanner reconstructs a 3D image from 150 2D images. A tracked mechanical arm mounted to the scanner locates four fiducial points on the template, registering the template to the 3D image. 3D reconstruction was validated for linear and volumetric measurement accuracy using phantoms of known geometry. In vivo breast US image quality was evaluated in a healthy volunteer. The encoded arm was calibrated and validated using a jig with divots at known locations relative to the scanner and the scanner registered to the 3D US image using intersecting strings in a fluid-filled test jig. Template registration accuracy was assessed using a machined test jig. Tracking accuracy was assessed in a liquid medium by comparing tracked and imaged needle tip positions. Finally, the system was used to guide a mock procedure in a patient-specific phantom and micro-CT imaging used to evaluate its accuracy. RESULTS: Geometric validation showed median distances within +/-1.1% of expected values and volumetric validation showed differences of <=4.1%. Tracking arm point measurements showed an average error of 0.43 mm and 3D US volume registration showed target registration error <=0.9 mm. Mean template registration accuracy in each axis of translation/rotation was <=1.3 mm/1.0 degrees . Mean needle targeting error was 2.5 mm and 1.6 degrees for needle tips and trajectories, respectively. Mean needle tip and angular errors of the phantom procedure were 2.1 mm and 2.6 degrees . Modeled seed displacement of the phantom procedure showed mean error of 2.6 mm and a maximum of 3.8 mm. CONCLUSIONS: A 3D US guidance system for PBSI has been developed. Benchtop performance and image quality in volunteer scans are satisfactory. A phantom PBSI procedure was successfully delivered using the system with maximum seed error within dosimetric benchmarks (<5 mm). Translation of the device into the clinic is forthcoming. PMID- 29791030 TI - Antiepileptic drugs as prophylaxis for postcraniotomy seizures. AB - BACKGROUND: This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). OBJECTIVES: To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. SEARCH METHODS: For the latest update we searched the following databases on 26 June 2017: Cochrane Epilepsy Group Specialized Register, the CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions. SELECTION CRITERIA: We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. DATA COLLECTION AND ANALYSIS: Three review authors (JW, JG, YD) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots. MAIN RESULTS: We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence.Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability.We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. AUTHORS' CONCLUSIONS: There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients. PMID- 29791032 TI - Social egg freezing-Better early than never. PMID- 29791031 TI - Ocean acidification stimulates particulate organic carbon accumulation in two Antarctic diatom species under moderate and high natural solar radiation. AB - Impacts of rising atmospheric CO2 concentrations and increased daily irradiances from enhanced surface water stratification on phytoplankton physiology in the coastal Southern Ocean remain still unclear. Therefore, in the two Antarctic diatoms Fragilariopsis curta and Odontella weissflogii, the effects of moderate and high natural solar radiation combined with either ambient or future pCO2 on cellular particulate organic carbon (POC) contents and photophysiology were investigated. Results showed that increasing CO2 concentrations had greater impacts on diatom physiology than exposure to increasing solar radiation. Irrespective of the applied solar radiation regime, cellular POC quotas increased with future pCO2 in both diatoms. Lowered maximum quantum yields of photochemistry in PSII (Fv /Fm ) indicated a higher photosensitivity under these conditions, being counteracted by increased cellular concentrations of functional photosynthetic reaction centers. Overall, our results suggest that both bloom forming Antarctic coastal diatoms might increase carbon contents under future pCO2 conditions despite reduced physiological fitness. This indicates a higher potential for primary productivity by the two diatom species with important implications for the CO2 sequestration potential of diatom communities in the future coastal Southern Ocean. PMID- 29791033 TI - Diabetes-related lower-extremity complications are a leading cause of the global burden of disability. AB - Globally ~435 million people have diabetes [1], and an estimated 19-34% (~83-148 million people) of those will be expected to develop foot ulcers in their lifetime [2]. Foot ulcers are typically precipitated by other diabetes-related lower-extremity complications, (DRLECs) including peripheral neuropathy and peripheral vascular disease [2,3]. Collectively, DRLECs are a leading cause of infection, hospitalization and amputation outcomes [2-5], yet, these outcomes are readily preventable with evidence-based care [6,7]. This suggests the burden caused by DRLECs is a large, yet reducible, cause of the global burden of disease. This article is protected by copyright. All rights reserved. PMID- 29791034 TI - High expression of CD10 in anaplastic thyroid carcinomas. AB - AIMS: CD10 is an endopeptidase that degrades various bioactive peptides in the extracellular matrix. In addition to enzymatic degradation, it affects multiple intracellular signal transduction pathways. CD10 expression has been extensively studied in human epithelial cancers of numerous organs and sites. However, its presence in thyroid carcinomas, especially in anaplastic thyroid carcinoma (ATC), has not been fully determined. An actual CD10 expression in thyroid lesions including a large series of ATC was evaluated. METHODS AND RESULTS: We examined CD10 by immunohistochemistry (IHC) in 152 thyroid lesions: nine adenomatous goitres (AGs) and 143 tumours, including 47 anaplastic carcinomas. IHC showed diffuse and strong positivity for CD10 in the epithelial components of almost all ATCs. However, epithelia with squamous metaplasia and oncocytic change from AGs, follicular adenomas and differentiated carcinomas had focal CD10 reactivity. Some papillary thyroid carcinomas (PTCs), along with the PTC components of some ATCs, showed CD10 positivity in fibroblast-like stromal cells and fibrous material. CONCLUSION: Our results imply that the CD10 expression pattern depended on the histotypes of thyroid lesions. When possible metastatic tumours and non epithelial tumours are excluded, high CD10 expression may be useful in determining whether a primary thyroid carcinoma includes an anaplastic component. PMID- 29791035 TI - Uncovering cryptic diversity of Lyngbya: the new tropical marine cyanobacterial genus Dapis (Oscillatoriales). AB - Cyanobacteria comprise an extraordinarily diverse group of microorganisms and, as revealed by increasing molecular information, this biodiversity is even more extensive than previously estimated. In this sense, the cyanobacterial genus Lyngbya is a highly polyphyletic group composed of many unrelated taxa with morphological similarities. In this study, the new genus Dapis was erected from the genus Lyngbya, based on a combined molecular, chemical, and morphological approach. Herein, two new species of cyanobacteria are described: D. pleousa and D. pnigousa. Our analyses found these species to be widely distributed and abundant in tropical and subtropical marine habitats. Seasonally, both species have the ability to form extensive algal blooms in marine habitats: D. pleousa in shallow-water, soft bottom habitats and D. pnigousa on coral reefs below depths of 10 m. Electron microscopy showed that D. pleousa contains gas vesicles, a character not previously reported in Lyngbya. These gas vesicles, in conjunction with a mesh-like network of filaments that trap oxygen released from photosynthesis, provide this species with an unusual mechanism to disperse in coastal marine waters, allowing D. pleousa to be present in both benthic and planktonic forms. In addition, both D. pleousa and D. pnigousa contained nitrogen fixing genes as well as bioactive secondary metabolites. Several specimens of D. pnigousa biosynthesized the secondary metabolite lyngbic acid, a molecule that has also been isolated from many other marine cyanobacteria. Dapis pleousa consistently produced the secondary metabolite malyngolide, which may provide a promising chemotaxonomic marker for this species. PMID- 29791036 TI - Neuroplasticity in cholinergic neurons of the laterodorsal tegmental nucleus contributes to the development of cocaine addiction. AB - The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus that sends cholinergic, glutamatergic, and gamma-aminobutyric acid (GABA)-ergic projections to the ventral tegmental area (VTA), a key brain region associated with reward information processing and reinforcement learning, and thus, with addiction induced by drugs of abuse, including cocaine. Recent studies have revealed that the LDT, in addition to the VTA, plays important roles in the development and expression of cocaine-induced addiction and stress-induced enhancement of addictive behaviors. Additionally, neuroplasticity induced in LDT cholinergic neurons by repeated cocaine administration critically contributes to these behaviors. Elucidation of the underlying mechanisms of cocaine-induced neuroplasticity in the LDT that influences reward circuit activity may lead to the development of therapeutic strategies to treat cocaine addiction and stress induced reinstatement of cocaine use. This review summarizes recent progress in the study of the LDT, specifically neuroplasticity in LDT cholinergic neurons induced by cocaine and its functional roles in the development and modulation of addictive behaviors associated with cocaine. PMID- 29791037 TI - Discrepancies Between Retrospective and Actual Self-Reports of Peer Victimization Six Years Earlier. AB - Retrospective peer victimization reports may be inaccurate. With an ethnically and sexually diverse sample, this study compared adolescents' self-reported peer victimization in 6th grade to their own retrospective reports of 6th-grade victimization when they were in the 12th grade, controlling for past and current adjustment. Overall, 12th graders' retrospective victimization reports correlated with their own earlier 6th-grade self-reports and there was a general tendency to underreport retrospectively. Underreporters were distinguished by worse past 6th grade adjustment, whereas overreporters were distinguished by worse current (12th grade) adjustment. Higher current depressive symptoms and social anxiety, and lower current self-worth may be important control variables when collecting retrospective reports of victimization because current adjustment may augment participants' recollection of past experiences. PMID- 29791038 TI - Special issue: Proceedings of 16th international conference on chiroptical spectroscopy, Rennes 2017. PMID- 29791039 TI - Racial differences in completion of the living kidney donor evaluation process. AB - Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live <=50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.26 0.47 0.83; P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.41 0.620.94; P = .02) and from clearance to donation (aHR: 0.28 0.510.91; P = .02), compared with from referral to medical screening (aHR: 0.78 1.021.33; P = .95) and from in-person evaluation to clearance (aHR: 0.59 0.931.44; P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities. PMID- 29791040 TI - Presence of chronic diabetic foot ulcers is associated with more frequent and more advanced retinopathy. AB - AIMS: To clarify the frequency and severity of diabetic retinopathy in a group of people with Type 2 diabetes and chronic diabetic foot ulcers, and to compare visual acuity, levels of retinopathy and clinical significant macular oedema with a matched control group of people with Type 2 diabetes without a history of chronic diabetic foot ulcers. METHODS: Visual acuity and fundus imaging were evaluated in 90 white people with at least 3 months' duration of full-thickness diabetic foot ulcers below the ankle and the results compared with those in 180 white people with Type 2 diabetes without a history of chronic diabetic foot ulcers (control group). Controls were matched for age, sex and duration of diabetes. RESULTS: Despite similar age and diabetes duration, severe non proliferative or proliferative diabetic retinopathy was present in 41% of the people in the diabetic foot ulcer group as compared to 15% in the control group (P<0.001). Only 6% in the diabetic foot ulcer group was without any diabetic retinopathy as compared to 34% among controls. Proliferative diabetic retinopathy was more common in the diabetic foot ulcer group (31% vs 8%; P<0.001), but time to-proliferative diabetic retinopathy did not differ between groups. Clinically significant macular oedema was more frequently present, and the diabetic foot ulcer group exhibited significantly worse results in best and worst eye visual acuity testing. CONCLUSIONS: In this northern European setting almost all people with Type 2 diabetes and chronic diabetic foot ulcers had diabetic retinopathy. Almost one-third had proliferative diabetic retinopathy as compared to <10% in our matched control group. More advanced diabetic retinopathy was linked to worse visual acuity. PMID- 29791042 TI - Behavioural state-specific neurons in the mouse medulla involved in sleep-wake switching. AB - The medullary reticular formation (RF) is involved in the maintenance of several vital physiological functions and level of vigilance. In this study, in nonanesthetised, head-fixed mice, I examined the role of medullary RF neurons in the control of sleep-wake states, that is, wakefulness (W), slow-wave sleep (SWS) and paradoxical (or rapid eye movement) sleep (PS). I showed, for the first time, that the mouse medullary RF contains presumed SWS-promoting, SWS-on neurons that remain silent during W, display a sharp increase in discharge rate at sleep onset, and discharge tonically and selectively during SWS. In addition, I showed the presence in the medullary RF of both PS-on and PS-off neurons, which, respectively, commence discharging or cease firing selectively just prior to, and during, PS. PS-off neurons were located in the raphe nuclei and ventral medulla, while PS-on neurons were found in both the lateral part of the ventral gigantocellular reticular nucleus and the raphe nuclei, as were SWS-on neurons. PS-off and SWS-on neurons appear to play an important role in both the W-SWS and SWS-PS switches, while PS-on and PS-off neurons play an important role in the PS W switch. The present findings on the trends in spike activity at the transitions from SWS to PS and from PS to W are in line with the reciprocal interaction hypothesis according to which PS occurs as a result of the cessation of discharge of PS-off neurons, while PS ends as a result of the start of discharge of PS-off neurons. PMID- 29791041 TI - Polymorphism, Weak Interactions and Phase Transitions in Chalcogen-Phosphorus Heterocycles. AB - A series of P-E-containing heterocycles (E=chalcogen) with aromatic backbones were synthesised and characterised by single-crystal and powder XRD, microanalysis and mass spectrometry. Solution- and solid-state 31 P and 77 Se NMR spectroscopy revealed significant differences between the NMR parameters in solution and in the solid state, related to conformational changes in the molecules. Many compounds were shown to exhibit a number of different polymorphic structures (identified by single-crystal XRD), although the bulk material studied by solid-state NMR spectroscopy often contained just one major polymorph. For the unoxidised heterocycles, the presence of weak intermolecular J couplings was also investigated by DFT calculations. PMID- 29791043 TI - Infection with ibrutinib in patients with chronic lymphocytic leukemia: How strong is the association? PMID- 29791044 TI - What happens to offspring when parents are inbred, old or had a poor start in life? Evidence for sex-specific parental effects. AB - Parental effects on offspring performance have been attributed to many factors such as parental age, size and condition. However, we know little about how these different parental characteristics interact to determine parental effects, or the extent to which their effect on offspring depends on either the sex of the parent or that of the offspring. Here we experimentally tested for effects of variation in parents' early diet and inbreeding levels, as well as effects of parental age, and for potential interactive effects of these three factors on key aspects of offspring development in the mosquitofish (Gambusia holbrooki). Older mothers produced offspring that were significantly smaller at birth. This negative effect of maternal age on offspring size was still evident at maturation as older mothers had smaller daughters, but not smaller sons. The daughters of older mothers did, however, reach maturity sooner. Paternal age did not affect offspring body size, but it had a complex effect on their sons' relative genital size. When initially raised on a food-restricted diet, older fathers sired sons with relatively smaller genitalia, but when fathers were initially raised on a control diet their sons had relatively larger genitalia. The inbreeding status of mothers and fathers had no significant effects on any of the measured offspring traits. Our results indicate that the manifestation of parental effects can be complex. It can vary with both parent and offspring sex; can change over an offspring's life; and is sometimes evident as an interaction between different parental traits. Understanding this complexity will be important to predict the role of parental effects in adaptation. PMID- 29791045 TI - Person-specific validation and testing of functional relations in cognitive behavioural case formulation: Guidelines and options. AB - Although a number of manuals describe how to develop a cognitive-behavioural case formulation (CBCF) to assist the clinician in developing and implementing tailored CB treatment for complex or comorbid cases, methods to evaluate and test functional hypotheses in the formulation for a particular case are not widely known or used. Thus, formulation-based, tailored treatments for such cases are likely to be guided by case formulations of uncertain validity. The present article presents guidelines and choices available to the clinical trainee, researcher, or practitioner planning to use a person-specific (PS) approach to testing CBCF hypotheses about functional relations between triggers, cognitions, and distress or dysfunction. This approach involves repeated assessments completed by the client using an individualized questionnaire that includes both nomothetic and idiographic items of greatest relevance to the client. Guidelines and options for developing this questionnaire and for data collection within the context of a collaborative therapist-client relationship are described. PS data analyses are then used to test case formulation hypotheses that vary in complexity from simple bivariate relations to complex dynamic mediation. A case example using this PS approach is described. Simpler options for the PS evaluation of a CBCF usable by practitioners and trainees as well as more complex options for clinical researchers are included. PMID- 29791046 TI - Impact of intensive dosing of mycophenolate on pancreas allograft survival. AB - PURPOSE: To evaluate the effect of mycophenolate (mycophenolic acid, MPA) dose on pancreas allograft survival following simultaneous pancreas kidney (SPK) transplant. METHODS: This was an observational study of adult SPK recipients transplanted between 1/1/2002 and 6/30/2015. Recipients were divided into cohorts based on MPA dose at discharge: high dose (HD), 1000 mg three times daily mycophenolate mofetil (MMF) and standard dose (SD), 1000 mg twice daily MMF. Primary outcome was pancreas allograft survival. Secondary endpoints included kidney allograft survival, pancreas allograft rejection, infection, time to initial dose decrease, and patient survival (PS). RESULTS: In all, 453 patients met inclusion criteria: 324 in HD-MPA group and 129 in SD-MPA group. HD-MPA patients had higher rates of pancreas graft survival (P = .003). There were no differences in rates of pancreas allograft rejection (P = .8), kidney graft survival (P = .15), overall infection (P = .4), overall malignancy (P = .93), time to first dose reduction (P = .35), or patient survival (P = .3). In a multivariable analysis adjusted for differences between groups and known confounders, dosing group continued to significantly affect incidence of pancreas allograft failure (P = .02). CONCLUSIONS: HD-MPA significantly impacted pancreas allograft survival in SPK recipients independent of graft rejection. Further studies are warranted to investigate the etiology of this finding and determine the optimal duration of HD-MPA associated with positive graft outcomes. PMID- 29791047 TI - Cell-Surface Engineering for Advanced Cell Therapy. AB - Stem cells opened great opportunity to overcome diseases that conventional therapy had only limited success. Use of scaffolds made from biomaterials not only helps handling of stem cells for delivery or transplantation but also supports enhanced cell survival. Likewise, cell encapsulation can provide stability for living animal cells even in a state of separateness. Although various chemical reactions were tried to encapsulate stolid microbial cells such as yeasts, a culture environment for the growth of animal cells allows only highly biocompatible reactions. Therefore, the animal cells were mostly encapsulated in hydrogels, which resulted in enhanced cell survival. Interestingly, major findings of chemistry on biological interfaces demonstrate that cell encapsulation in hydrogels have a further a competence for modulating cell characteristics that can go beyond just enhancing the cell survival. In this review, we present a comprehensive overview on the chemical reactions applied to hydrogel-based cell encapsulation and their effects on the characteristics and behavior of living animal cells. PMID- 29791048 TI - Long-term course of inflammatory bowel disease after the Great East Japan Earthquake. AB - BACKGROUND AND AIM: This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. METHODS: We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. RESULTS: Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. CONCLUSIONS: The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse. PMID- 29791049 TI - 2-Benzoylpyridine Ligand Complexation with Gold Critical for Propargyl Ester Based Protein Labeling. AB - In previously reported work, AuIII complexes coordinated with 2-benzoylpyridine ligand, BPy-Au, were prebound to a protein and used to discover a novel protein directed labeling approach with propargyl ester functional groups. In this work, further examination discovered that gold catalysts devoid of the 2 benzoylpyridine ligand (e.g., NaAuCl4) had significantly reduced levels of protein labeling. Mechanistic investigations then revealed that BPy-Au and propargyl esters undergo a rare example of C(sp2 )-C(sp) aryl-alkynyl cross coupling, likely through spontaneous reductive elimination. Overall, these observations appear to suggest that BPy-Au-mediated, propargyl ester-based protein labeling acts via an activated ester intermediate, which contributes to our understanding of this process and will aid the expansion/optimization of gold catalyst usage in future bioconjugation applications, especially in vivo. PMID- 29791050 TI - A novel CLCN5 pathogenic mutation supports Dent disease with normal endosomal acidification. AB - Dent disease is an X-linked recessive renal tubular disorder characterized by low molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. Inactivating mutations of CLCN5, the gene encoding the 2Cl- /H+ exchanger ClC-5, have been reported in patients with Dent disease 1. In vivo studies in mice harboring an artificial mutation in the "gating glutamate" of ClC-5 (c.632A > C, p.Glu211Ala) and mathematical modeling suggest that endosomal chloride concentration could be an important parameter in endocytosis, rather than acidification as earlier hypothesized. Here, we described a novel pathogenic mutation affecting the "gating glutamate" of ClC-5 (c.632A>G, p.Glu211Gly) and investigated its molecular consequences. In HEK293T cells, the p.Glu211Gly ClC-5 mutant displayed unaltered N-glycosylation and normal plasma membrane and early endosomes localizations. In Xenopus laevis oocytes and HEK293T cells, we found that contrasting with wild-type ClC-5, the mutation abolished the outward rectification, the sensitivity to extracellular H+ and converted ClC-5 into a Cl- channel. Investigation of endosomal acidification in HEK293T cells using the pH-sensitive pHluorin2 probe showed that the luminal pH of cells expressing a wild-type or p.Glu211Gly ClC-5 was not significantly different. Our study further confirms that impaired acidification of endosomes is not the only parameter leading to defective endocytosis in Dent disease 1. PMID- 29791051 TI - From learning to action: the integration of dorsal striatal input and output pathways in instrumental conditioning. AB - Considerable evidence suggests that the learning and performance of instrumental actions depend on activity in basal ganglia circuitry; however, these two functions have generally been considered independently. Whereas research investigating the associative mechanisms underlying instrumental conditioning has identified critical cortical and limbic input pathways to the dorsal striatum, the performance of instrumental actions has largely been attributed to activity in the dorsal striatal output pathways, with direct and indirect pathway projection neurons mediating action initiation, perseveration and cessation. Here, we discuss evidence that the dorsal striatal input and basal ganglia output pathways mediate the learning and performance of instrumental actions, respectively, with the dorsal striatum functioning as a transition point. From this perspective, the issue of how multiple striatal inputs are integrated at the level of the dorsal striatum and converted into relatively restricted outputs becomes one of critical significance for understanding how learning is translated into action. So too does the question of how learning signals are modulated by recent experience. We propose that this occurs through recurrent corticostriatothalamic feedback circuits that serve to integrate performance signals by updating ongoing action-related learning. PMID- 29791052 TI - High-performance liquid chromatography quantification of enantiomers of a Dihydroxylated tetrahydrofuran natural product. AB - Both enantiomers of petromyroxol are putative pheromones in sea lamprey (Petromyzon marinus). Here, we describe the separation and quantification of the petromyroxol enantiomers using high-performance liquid chromatography tandem mass spectrometry. The separation was tested on a wide range of chiral columns with normal phases, and effects of the chromatographic parameters such as mobile phase and temperature on the separation were optimized. The AD-H column showed the best separation of enantiomers with n-hexane and ethanol as the mobile phase. The enantiomers were detected by multiple reaction monitoring with a positive atmospheric-pressure chemical ionization on triple quadrupole mass spectrometer. Validation revealed that the method was specific, accurate, and precise. The validated method was applied to measure the amount of petromyroxol enantiomers in water conditioned with sea lamprey larvae, the source of the putative pheromone. This method will be applied in quantifying the natural scalemic petromyroxol mixture, enabling further investigations of a rare non-racemic enantiomeric pheromone mixture in a vertebrate species. PMID- 29791053 TI - Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. AB - INTRODUCTION: Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown. PATIENTS AND METHODS: We reported on 159 myelofibrosis patients (pts) with a median age of 59 years (r: 28-74) who received reduced intensity ASCT between 2000 and 2015 in eight German centers from related (n = 23), matched (n = 86) or mismatched (n = 50) unrelated donors. Forty-six (29%) patients received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30 mg (range 10-40 mg) and the median duration of treatment was 4.9 months (range 0.4-39.1 months). RESULTS: Primary graft failure was seen in 2 pts (4%) in the ruxolitinib and 3 (2%) in the non ruxolitinib group. Engraftment and incidence of acute GVHD grade II to IV and III/IV did not differ between groups (37% vs 39% and 19% vs 28%, respectively), nor did the non-relapse mortality at 2 years (23% vs 23%). A trend for lower risk of relapse was seen in the ruxolitinib group (9% vs 17%, P = .2), resulting in a similar 2 year DFS and OS (68% vs 60% and 73% vs 70%, respectively). No difference in any outcome variable could be seen between ruxolitinib responders and those who failed or lost response to ruxolitinib. CONCLUSIONS: These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation. PMID- 29791054 TI - Incidence of childhood Type 1 diabetes mellitus in Crete. AB - AIM: To investigate the epidemiology of childhood Type 1 diabetes mellitus in Crete over the last 25 years and to evaluate incidence trends over time. METHODS: The study included all children aged 0-14 years who live in Crete and were diagnosed during the 25-year period from 1 January 1992 to 31 December 2016. RESULTS: A total of 271 children were diagnosed with Type 1 diabetes during the 25-year period: 148 boys and 123 girls (boy:girl ratio 1.2). The median (interquartile range) age at diagnosis was 8.3 (5.0-12.0) years for boys and 8.0 (5.3-11.3) years for girls. The standardized annual incidence rate was 10.5 per 100 000 children (95% CI 9.2 to 11.8). Incidence rates were higher in children aged 5-9 years. During the 25-year study period an average 4.4% annual increase in incidence was documented and was most prominent in the age group 5-14 years. Incidence seemed to remain relatively stable for the age group 0-4 years in the last decade. No seasonality of the clinical onset of Type 1 diabetes was observed. CONCLUSIONS: The recent increase in Type 1 diabetes incidence places Crete among regions with high incidence as per the World Health Organization DiaMond project classification. The rising trends in incidence confirmed by this study are in accordance with the reported global trends in Type 1 diabetes incidence. PMID- 29791055 TI - High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood. AB - AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34 40. METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975 1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within +/-1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries. RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher. CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight. PMID- 29791056 TI - Dactylomonas gen. nov., a Novel Lineage of Heterolobosean Flagellates with Unique Ultrastructure, Closely Related to the Amoeba Selenaion koniopes Park, De Jonckheere & Simpson, 2012. AB - We report the discovery of a new genus of heterolobosean flagellates, Dactylomonas gen. nov., with two species, D. venusta sp. nov. and D. crassa sp. nov. Phylogenetic analysis of the SSU rRNA gene showed that Dactylomonas is closely related to the amoeba Selenaion, the deepest-branching lineage of Tetramitia. Dactylomonads possess two flagella, and ultrastructural studies revealed an unexpected organization of the flagellar apparatus, which resembled Pharyngomonada (the second lineage of Heterolobosea) instead of Tetramitia: basal bodies were orthogonal to each other and a putative root R1 was present in the mastigont. On the other hand, Dactylomonas displayed several features uncommon in Heterolobosea: a microtubular corset, a distinctive rostrum supported by the main part of the right microtubular root, a finger-like projection on the proximal part of the recurrent flagellum, and absence of a ventral groove. In addition, Dactylomonas is anaerobic and seems to have lost mitochondrial cristae. Dactylomonas and Selenaion are accommodated in the family Selenaionidae fam. nov. and order Selenionida ord. nov. The taxonomy of Tetramitia is partially revised, and the family Neovahlkampfiidae fam. nov. is established. PMID- 29791057 TI - Refining noninvasive support strategies to help babies breathe. PMID- 29791058 TI - Gene flow does not prevent personality and morphological differentiation between two blue tit populations. AB - Understanding the causes and consequences of population phenotypic divergence is a central goal in ecology and evolution. Phenotypic divergence among populations can result from genetic divergence, phenotypic plasticity or a combination of the two. However, few studies have deciphered these mechanisms for populations geographically close and connected by gene flow, especially in the case of personality traits. In this study, we used a common garden experiment to explore the genetic basis of the phenotypic divergence observed between two blue tit (Cyanistes caeruleus) populations inhabiting contrasting habitats separated by 25 km, for two personality traits (exploration speed and handling aggression), one physiological trait (heart rate during restraint) and two morphological traits (tarsus length and body mass). Blue tit nestlings were removed from their population and raised in a common garden for up to 5 years. We then compared adult phenotypes between the two populations, as well as trait-specific Qst and Fst . Our results revealed differences between populations similar to those found in the wild, suggesting a genetic divergence for all traits. Qst -Fst comparisons revealed that the trait divergences likely result from dissimilar selection patterns rather than from genetic drift. Our study is one of the first to report a Qst -Fst comparison for personality traits and adds to the growing body of evidence that population genetic divergence is possible at a small scale for a variety of traits including behavioural traits. PMID- 29791059 TI - Use of high-resolution colonic manometry to establish etiology and direct treatment in patients with constipation: Case series with correlation to histology. AB - BACKGROUND AND AIM: Different clinical treatments are available to treat patients with constipation. We aimed to study the etiology and direct treatment in a case series of patients with constipation by the use of high-resolution colonic manometry (HRCM). METHODS: High-resolution colonic manometry was used to record the colorectal peristaltic contractions of the entire colon in patients. Based on the results of HRCM, 151 patients with constipation were classified into groups and received different clinical treatment such as a total or subtotal colectomy, local excision, or conservative treatment. Paraffin-embedded samples obtained after resection were studied using hematoxylin and eosin, as well as immunohistochemical staining. RESULTS: All patients underwent HRCM over 24 h. Based on the amplitude, intensity, and trends in peristaltic contractions recorded by HRCM, we observed 117 patients with slow-transit constipation and 34 with functional outlet obstruction constipation. After an overall evaluation of the results of HRCM and anorectal function, 26, 23, 27, and 75 patients were treated with total colectomy, subtotal colectomy, local excision, and conservative treatment, respectively. Furthermore, histological examination of surgical samples showed vacuolar degeneration of nerve plexuses as well as of the muscularis propria, which also showed fibrosis in its outer layers in patients with constipation. CONCLUSION: Different types of constipation showed different colonic motility patterns and morphological changes in the colonic wall. HRCM plays an important role in the diagnosis and classification of patients with constipation. Furthermore, HRCM can accurately identify the diseased colonic segments and help to choose the appropriate treatment. PMID- 29791060 TI - Implementing an innovated preservation technology: The American Society of Transplant Surgeons' (ASTS) Standards Committee White Paper on Ex Situ Liver Machine Perfusion. AB - The pervasive shortage of deceased donor liver allografts contributes to significant waitlist mortality despite efforts to increase organ donation. Ex vivo liver perfusion appears to enhance preservation of donor organs, extending viability and potentially evaluating function in organs previously considered too high risk for transplant. These devices pose novel challenges for organ allocation, safety, training, and finances. This white paper describes the American Society of Transplant Surgeons' belief that organ preservation technology is a vital advance, but its use should not change fundamental aspects of organ allocation. Additional data elements need to be collected, made available for organ assessment by transplant professionals to allow determination of organ suitability in the case of reallocation and incorporated into risk adjustment methodology. Finally, further work is needed to determine the optimal strategy for management and oversight of perfused organs prior to transplantation. PMID- 29791061 TI - Antidiuretic hormone release associated with increased intracranial pressure independent of plasma osmolality. AB - OBJECTIVE: Introduce and evaluate a new model which explains the release of brain antidiuretic hormone (ADH) independent of plasma osmolality. METHODS: Systematic review and critical analysis of the professional literature. RESULTS: Primary electronic database searches using key terms revealed 57,432 hits. Secondary searches with application of specific inclusion and exclusion criteria and manual inspection for completeness reduced the total number of studies to fourteen (N = 14). Twelve (N = 12) studies investigated human subjects in the hospital settings, and two (N = 2) studies investigated animals (rhesus monkeys and dog) under invasive experimental conditions. All fourteen studies included direct or indirect indicators of intracranial pressure (ICP), measurements of plasma ADH, and plasma osmolality or urine osmolality. Findings, in brief, reveal a stable and positive association between increased intracranial pressure (ICP) and increased ADH release, in patients with low or normal blood osmolality. Findings are reliable and reproducible across human and animal populations. CONCLUSIONS: Findings support the proposed model, which explains increase secretion of brain ADH when plasma osmolality is low or within normal limits. Mechanical pressures exerted on hypothalamic nuclei, especially paraventricular and supra-optic nuclei, as a consequence of increased intracranial pressure, produce release of ADH, independent of plasma osmolality. The mechanical pressure model explains release of ADH previously unexplained by traditional plasma osmolality models. Findings have important clinical implications for the medical and surgical management of patients. PMID- 29791062 TI - Antinocioceptive Effects of Spinal Cord Stimulation by Activation of Periaqueductal Gray Matter and Rostral Ventromedial Medulla: A Mechanism Beyond the Gate Control Theory. PMID- 29791063 TI - Ten-year follow-up of dental implants used for immediate loading in the edentulous mandible: A prospective clinical study. AB - PURPOSE: The purpose of this study is to evaluate the 10-year outcome of 25 patients with immediate loading in the edentulous mandible. MATERIAL AND METHODS: Twenty-five patients were consecutively treated with 5 immediately loaded fluoride-modified implants in the edentulous mandible. Implant survival and bone loss were evaluated by an external researcher comparing digital periapical radiographs taken during recall visits with baseline (at implant insertion). Statistical descriptive analysis and nonparametric tests were performed using SPSS v23, multilevel analysis was performed by means of R version 3.1.0. to identify risk factors for bone loss. RESULTS: Twenty-one patients (8 males, 13 females, mean age 68.4, range 49-84) responded to the 10-year recall invitation. No implants were lost during follow-up, resulting in a 100% survival rate. After 10 years, bleeding on probing and plaque were present at 49.5% and 67.6% of the sites, respectively. The mean pocket probing depth was 3.77 mm (SD 0.73, range 3.0-6.83). Bone loss on implant level after 3, 12, 24, and 120 months was 0.16 mm (SD 0.33, range 0-1.75), 0.14 mm (SD 0.24, range 0-1.05), 0.17 mm (SD 0.27, range 0-1.5), and 0.49 mm (SD 1.08, range 0-7.8). Five implants were identified with or at risk for progressive bone loss. Forty-seven percent of the implants did not show any bone loss after 10 years in function and 87% lost less than 1 mm. Multilevel statistical analysis identified 2-year bone loss as a predictor for bone loss after 10 years of function. CONCLUSION: Immediate loading of 5 fluoride modified dental implants with a fixed prosthetic rehabilitation is a predictable and reliable treatment in the edentulous mandible, based on a 100% implant survival and limited peri-implant bone loss. Implants used for immediate loading in the edentulous mandible who are showing early bone loss may be at higher risk to develop peri-implantitis. PMID- 29791064 TI - Abdomino-perineal excision for low rectal cancer performed by double laparoscopy approach with no position change - a video vignette. PMID- 29791065 TI - Risk Factors for Valproic Acid-induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy. AB - This study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic patients, treated with VPA as monotherapy, were enrolled and classified into hyperammonaemia and control groups according to their blood ammonia level (cut-off value 50 MUmol/L). Serum concentrations of VPA and its major metabolites were simultaneously determined by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Six single nucleotide polymorphisms in the candidate genes, CYP2C9, CYP2A6, CYP2B6 and CPS1, were analysed by a matrix-assisted laser desorption ionization-time of flight mass spectrometry method or nested PCR. Significant differences in age, aspartate transaminase level and the incidence of liver injury were observed between patients of hyperammonaemia and control groups. Genotype distributions of CYP2C9*3, CYP2A6*4 and CPS1 4217C>A allelic variants were also significantly different between the two groups. According to multiple regression analysis, a significant negative correlation was detected between age and the blood ammonia level, while liver injury, the concentration-dose ratio (CDR) of VPA and 2-propyl 4-pentenoic acid (4-ene VPA), and the presence of CYP2A6*4 or CPS1 4217C>A showed positive correlations with the blood ammonia level. In addition, the risk factors for hyperammonaemia identified by logistic regression analysis were as follows: a younger age (odds ratio [OR] = 0.85; 95% confidence interval [CI] = 0.76-0.96; p = 0.007), occurrence of liver injury (OR = 4.60; 95% CI = 1.27-16.74; p = 0.021), higher CDR of 4-ene VPA (OR = 1.08; 95% CI = 1.03-1.14; p = 0.001), and carrying mutant alleles of CYP2C9*3 (OR = 3.42; 95% CI = 1.15-10.19; p = 0.028), CYP2A6*4 (OR = 3.23; 95% CI = 1.40-7.48; p = 0.006) and CPS1 4217C>A (OR = 3.25; 95% CI = 1.52-6.94; p = 0.002). Our findings indicated that multiple genetic and non genetic risk factors that were identified can be used to predict the development of VPA-induced hyperammonaemia in Chinese paediatric patients with epilepsy. PMID- 29791066 TI - Application of denaturing capillary electrophoresis for the detection of prognostic mutations in isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 genes in brain tumors. AB - Malignant transformation in gliomas is frequently supplemented by somatic mutations in isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 genes. It has recently emerged that mutations in these genes are associated with prolonged survival and should be used as prognostic factor in management of brain cancer patients. There are several approaches in use for the detection of isocitrate dehydrogenase 1 and 2 mutations; however, these often exhibit shortcomings such as convoluted protocols with long processing time, complex (and costly) dedicated fluorescent probes, and/or demand on amounts of input DNA. Therefore, a simple and rapid method would be highly desired. Here, we present development and validation of simple and reliable isocitrate dehydrogenase 1 and 2 mutation detection assay using denaturing capillary electrophoresis. The detection sensitivity in terms of the limiting mutated allele fraction detectable estimated from a series of dilution runs was 2.9%. The method was validated by comparing to results obtained by a widely accepted detection technique, the multiplex ligation dependent probe amplification, on a set of 85 brain tumors. The concordance of both methods was 100%, but denaturing capillary electrophoresis assay required fivefold lower input of DNA (1 versus 5 MUL of DNA at concentrations typically between 10 and 30 ng/MUL). PMID- 29791067 TI - Synergistic-Catalysis-Enabled Reaction of 2-Indolymethanols with Oxonium Ylides for the Construction of 3-Indolyl-3-Alkoxy Oxindole Frameworks. AB - A synergistic-catalysis-enabled reaction of 2-indolymethanols with oxonium ylides has been established that makes use of a three-component reaction between 3 diazooxindoles, alcohols, and 2-indolymethanols under the cooperative catalysis of a metal complex and a Bronsted acid. This reaction has not only provided a new approach for the construction of 3-indolyl-3-alkoxy oxindole scaffolds by utilizing the C3-electrophilicity of an indole, but it is also the first example of a nucleophilic addition of a metal-associated ylide to 2-indolylmethanols. In addition, this reaction also includes a rarely reported trapping of onium ylides with aryl electrophiles. PMID- 29791068 TI - CDPBC: A Software Application for Estimation of Concentration Dependent Plasma Binding Capacity of Small Molecule. AB - Drug-plasma binding (DPB) is an important aspect during pharmacokinetics (PK) studies. DPB of small molecule cannot be evaluated through computational means. Here we present CDPBC; a standalone application for evaluation of small molecule for its capacity (concentration dependent) of binding with plasma proteins. This application is freely available at URL (https://github.com/undwive di/CDPBC.git). The application is enriched with evaluation of five major proteins of plasma. Input for application is a docked complex against the suggested PDBs of plasma proteins. As part of the analysis, software compares interaction of query compound with control compound. Main output comes as plot as well as table displaying percentage of binding in reference of concentration gradient of small molecule used in docking. The application is an advanced add-on component to ADME analysis of small molecules as well as lead optimization. PMID- 29791069 TI - Rethinking performance benchmarks in kidney transplantation. PMID- 29791070 TI - Role of oral examination in newly diagnosed multiple myeloma patients: A safe and simple way to detect light chain amyloidosis. AB - OBJECTIVE: Up to 30% of multiple myeloma (MM) patients have subclinical amyloid deposits. These patients are under-recognized and are more susceptible to drug toxicity, bleeding and death. Early diagnosis and adjustment of treatment are crucial. Biopsies of oral mucosa might be a potentially useful diagnostic tool. The objective of this study was to assess the prevalence and characteristics at presentation of oral amyloidosis in a large cohort of MM patients. METHODS: The prevalence and characteristics of oral amyloidosis in a large cohort of MM patients who were referred for oral evaluation before and during bisphosphonate therapy were assessed, retrospectively. RESULTS: Among 212 patients analysed, 13 (6%) were diagnosed with concomitant light chain (AL) amyloidosis. In 54% (n = 7), lesions in the oral cavity compatible with amyloid deposition were detected by examination. CONCLUSIONS: The salient feature of this study is the high prevalence of oral manifestations among MM patients with amyloidosis. These results highlight the value of routine oral cavity examination and biopsy as a safe and simple method for detecting light chain amyloidosis. PMID- 29791071 TI - Plastic rates of development and the effect of thermal extremes on offspring fitness in a cold-climate viviparous lizard. AB - Populations at the climatic margins of a species' distribution can be exposed to conditions that cause developmental stress, resulting in developmental abnormalities. Even within the thermal range of normal development, phenotypes often vary with developmental temperature (i.e., thermal phenotypic plasticity). These effects can have significant consequences for organismal fitness and, thus, population persistence. Reptiles, as ectotherms, are particularly vulnerable to thermal effects on development and are, therefore, considered to be at comparatively high risk from changing climates. Understanding the extent and direction of thermal effects on phenotypes and their fitness consequences is crucial if we are to make meaningful predictions of how populations and species will respond as climates warm. Here, we experimentally manipulated the thermal conditions experienced by females from a high-altitude, cold-adapted population of the viviparous skink, Niveoscincus ocellatus, to examine the consequences of thermal conditions at the margins of this population's normal temperature range. We found strong effects of thermal conditions on the development of key phenotypic traits that have implications for fitness. Specifically, we found that offspring born earlier as a result of high temperatures during gestation had increased growth over the first winter of life, but there was no effect on offspring survival, nor was there an effect of developmental temperature on the incidence of developmental abnormalities. Combined, our results suggest that advancing birth dates that result from warming climates may have positive effects in this population via increased growth. PMID- 29791072 TI - Massive hemothorax after computed tomography-guided lung tumor biopsy: An unusual but disastrous complication. AB - Intercostal artery injury during transthoracic puncture is rare but is accompanied by high rates of morbidity and mortality. We report a case with metachronous double primary esophageal cancers and development of multiple lung nodules. Tissue proof for the lung nodules is required to guide the following treatment protocol. Our patient died soon after computed tomography-guided lung tumor biopsy was performed, as a result of procedure-related massive and uncontrolled hemothorax. The cause is likely intercostal artery injury related to the transthoracic puncture. After review of our case and the wide variation in intercostal artery courses, we identify several considerations that should be included in procedural planning to further decrease the risk of intercostal artery injury during transthoracic puncture, including avoiding choosing target lesions at the posterior lung, keeping the puncture needle as close to the superior rib margin as possible, and checking the density of new pleural fluid. In addition, it is important to inform clinical doctors when the risk of periprocedural vascular injury is high. PMID- 29791073 TI - Elevated histone H3 acetylation is associated with genes involved in T lymphocyte activation and glutamate decarboxylase antibody production in patients with type 1 diabetes. AB - AIMS/INTRODUCTION: Genetic and epigenetic mechanisms have been implicated in the pathogenesis of type 1 diabetes, and histone acetylation is an epigenetic modification pattern that activates gene transcription. However, the genome-wide histone H3 acetylation in new-onset type 1 diabetes patients has not been well described. Accordingly, we aimed to unveil the genome-wide promoter acetylation profile in CD4+ T lymphocytes from type 1 diabetes patients, especially for those who are glutamate decarboxylase antibody-positive. MATERIALS AND METHODS: A total of 12 patients with new-onset type 1 diabetes who were glutamate decarboxylase antibody-positive were enrolled, and 12 healthy individuals were recruited as controls. The global histone H3 acetylation level of CD4+ T lymphocytes from peripheral blood was detected by western blot, with chromatin immunoprecipitation linked to microarrays to characterize the promoter acetylation profile. Furthermore, we validated the results of particular genes from chromatin immunoprecipitation linked to microarrays by using chromatin immunoprecipitation quantitative polymerase chain reaction, and analyzed the transcription level by real-time quantitative polymerase chain reaction. RESULTS: Elevated global histone H3 acetylation level was observed in type 1 diabetes patients, with 607 differentially acetylated genes identified between type 1 diabetes patients and controls by chromatin immunoprecipitation linked to microarrays. The hyperacetylated genes were enriched in biological processes involved in immune cell activation and inflammatory response. Gene-specific assessments showed that increased transcription of inducible T-cell costimulator was in concordance with the elevated acetylation in its gene promoter, along with positive correlation with glutamate decarboxylase antibody titer in type 1 diabetes patients. CONCLUSIONS: The present study generates a genome-wide histone acetylation profile specific to CD4+ T lymphocytes in type 1 diabetes patients who are glutamic acid decarboxylase antibody-positive, which is instrumental in improving our understanding of the epigenetic involvement in autoimmune diabetes. PMID- 29791074 TI - Access to the Enantiopure Axially Chiral Cyclophane Isoplagiochin D through Atropo-diastereoselective Heck Coupling. AB - Macrocyclization is typically the key step in the syntheses of cyclophane-type natural products. Considering cyclophanes with axially chiral biaryl moieties, the control of atroposelectivity is essential with biological activity and is synthetically challenging. We report an atroposelective approach involving Heck cyclization, which for the first time enables the total synthesis of an enantiopure macrocyclic bis(bibenzyl), namely isoplagiochin D. An enantiopure sulfinyl auxiliary in the ortho position of a biaryl axis (still flexible) was used to induce an atropo-diastereoselective Heck coupling (up to 98 % de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with 98 % ee as well. PMID- 29791075 TI - Erythrocyte sedimentation rate measured using microhemagglutination is not elevated in monoclonal gammopathy compared with other diseases. AB - BACKGROUND: The erythrocyte sedimentation rate (ESR) as measured using the Westergren method is extremely elevated in patients with monoclonal gammopathy (MG) owing to the abundance of positively charged paraproteins. However, it has not been determined if the ESR is likewise high in patients with MG when measured using alternate ESR methods. METHODS: The ESR was measured using both the modified Westergren and microhemagglutination method (TEST1) in 36 patients with MG and in 159 individuals with other diseases. RESULTS: Erythrocyte sedimentation rates measured by the Westergren vs microhemagglutination methods showed substantial, but not remarkably high correlation. ESR measured using the Westergren method was higher in MG than in non-MG patients; however, ESR measured using microhemagglutination was not different in the 2 groups, resulting in a larger DeltaESR (microhemagglutination ESR-Westergren ESR) in MG patients. When considered as continuous variables, none of the tested interfering plasma proteins (C-reactive protein, globulin, or fibrinogen) showed substantial correlations with Westergren or microhemagglutination ESRs. MG and low hematocrit were the only factors independently associated with DeltaESR on multivariate analysis. CONCLUSION: We demonstrated, for the first time, that the ESR as measured by microhemagglutination is not elevated in patients with MG compared with those without. The ESR does not correlate with a particular plasma protein, showing that its measurement is multifactorial. The presence of MG is an independent factor for DeltaESR. PMID- 29791076 TI - Effects of endurance training on hippocampus DJ-1, cannabinoid receptor type 2 and blood glucose concentration in diabetic rats. AB - AIMS/INTRODUCTION: To investigate the effect of endurance training on hippocampus DJ-1 and cannabinoid receptor type 2 (CB2 ) protein and blood glucose concentration in diabetic rats. MATERIALS AND METHODS: A total of 32 rats were randomly divided into diabetic (D), diabetic and exercise (DE), exercise (E) and control (C) groups. The endurance training was carried out five times per week for 6 weeks. The hippocampus DJ-1 and CB2 were measured using an enzyme-linked immunosorbent assay method. RESULTS: The level of DJ-1 in the D group was significantly higher than the other groups (P <= 0.01). However, the level of DJ 1 was not significantly different between the C, E and DE groups. In addition, the level of CB2 was significantly lower in the D group compared with the other groups (P <= 0.01). Blood glucose was significantly higher in the D group compared with the DE group (P <= 0.05). Furthermore, a significant positive correlation between the level of DJ-1 and blood glucose was observed (r = 0.67, P <= 0.001). There was also a significant inverse correlation between the level of CB2 and blood glucose (r = -0.77, P <= 0.001). CONCLUSIONS: The results of this study suggest that the level of DJ-1 and CB2 might change in response to diabetes, and regular aerobic exercise could mediate the effect of DJ-1 and CB2 on diabetes-induced neurodegenerative diseases. PMID- 29791077 TI - Alterations of brain network hubs in reflex syncope: Evidence from a graph theoretical analysis based on DTI. AB - OBJECTIVE: We evaluated global topology and organization of regional hubs in the brain networks and microstructural abnormalities in the white matter of patients with reflex syncope. METHODS: Twenty patients with reflex syncope and thirty healthy subjects were recruited, and they underwent diffusion tensor imaging (DTI) scans. Graph theory was applied to obtain network measures based on extracted DTI data, using DSI Studio. We then investigated differences in the network measures between the patients with reflex syncope and the healthy subjects. We also analyzed microstructural abnormalities of white matter using tract-based spatial statistics analysis (TBSS). RESULTS: Measures of global topology were not different between patients with reflex syncope and healthy subjects. However, in reflex syncope patients, the strength measures of the right angular, left inferior frontal, left middle orbitofrontal, left superior medial frontal, and left middle temporal gyrus were lower than in healthy subjects. The betweenness centrality measures of the left middle orbitofrontal, left fusiform, and left lingual gyrus in patients were lower than those in healthy subjects. The PageRank centrality measures of the right angular, left middle orbitofrontal, and left superior medial frontal gyrus in patients were lower than those in healthy subjects. Regarding the analysis of the white matter microstructure, there were no differences in the fractional anisotropy and mean diffusivity values between the two groups. CONCLUSIONS: We have identified a reorganization of network hubs in the brain network of patients with reflex syncope. These alterations in brain network may play a role in the pathophysiologic mechanism underlying reflex syncope. PMID- 29791078 TI - Molecular subtype classification of urothelial carcinoma in Lynch syndrome. AB - Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. PMID- 29791079 TI - Overexpression of Tet3 in donor cells enhances goat somatic cell nuclear transfer efficiency. AB - Ten-eleven translocation 3 (TET3) mediates active DNA demethylation of paternal genomes during mouse embryonic development. However, the mechanism of DNA demethylation in goat embryos remains unknown. In addition, aberrant DNA methylation reprogramming prevalently occurs in embryos cloned by somatic cell nuclear transfer (SCNT). In this study, we reported that TET3 is a key factor in DNA demethylation in goat pre-implantation embryos. Knockdown of Tet3 hindered DNA demethylation at the two- to four-cell stage in goat embryos and decreased Nanog expression in blastocysts. Overexpression of Tet3 in somatic cells can initiate DNA demethylation, reduce 5-methylcytosine level, increase 5 hydroxymethylcytosine level and promote the expression of key pluripotency genes. After SCNT, overexpression of Tet3 in donor cells corrected abnormal DNA hypermethylation of cloned embryos and significantly enhanced in vitro and in vivo developmental rate (P < 0.05). We conclude that overexpression of Tet3 in donor cells significantly improves goat SCNT efficiency. PMID- 29791081 TI - The Sanguicolous Apostome Metacollinia luciensis Jankowski 1980 (Colliniidae, Apostomatia, Ciliophora) Is Not Closely Related to Other Sanguicolous Apostomes. AB - The apostome family Colliniidae includes species that are adapted to the hemocoel/blood of various invertebrates, particularly crustaceans. To explore the phylogeny of these sanguicolous apostomes, Metacollinia luciensis was collected in August 2015 at Roscoff from the amphipod host, Orchestia gammarellus. Ciliates were Protargol stained and DNA was extracted. The small subunit rRNA (SSUrRNA) and cytochrome c oxidase subunit I (cox1) genes were amplified. Molecular phylogenetic analyses of the SSUrRNA genes unambiguously grouped M. luciensis with other apostomes with robust bootstrap support, but separated it distinctly from the pseudocolliniid clade. While there are only cox1 sequences for a subset of these apostomes, M. luciensis was also distant from the pseudocolliniids and separated from them by species of the exuviotrophic apostome Hyalophysa. These results confirm the distinctness of the families Colliniidae and Pseudocolliniidae. PMID- 29791080 TI - One-Step Lignocellulose Fractionation by using 2,5-Furandicarboxylic Acid as a Biogenic and Recyclable Catalyst. AB - To develop novel biorefinery concepts, the use of bio-based catalysts and solvents must be aligned with the principles of green chemistry. In this context, biogenic 2,5-furandicarboxylic acid (FDCA) is a very promising yet underused molecule with high potential for application as an acid catalyst, combining feasibility and sustainability with efficient and straightforward recovery. In this study, FDCA was evaluated as a catalyst in the recently developed OrganoCat pretreatment, a biphasic lignocellulose fractionation system. The catalyst was investigated for the efficient fractionation of the three main components-lignin, cellulose and noncellulosic sugars-with particular focus on the lignin quality, on the effect on enzymatic hydrolysis of the cellulosic residue, and on the noncellulosic sugar extraction. To address recovery of FDCA from the OrganoCat system, a method was developed, leading to the recovery of >97 % of FDCA with a spectroscopic purity of >99 %, maintaining full activity in consecutive runs. PMID- 29791082 TI - Higher Acenes by On-Surface Dehydrogenation: From Heptacene to Undecacene. AB - A unified approach to the synthesis of the series of higher acenes up to previously unreported undecacene has been developed through the on-surface dehydrogenation of partially saturated precursors. These molecules could be converted into the parent acenes by both atomic manipulation with the tip of a scanning tunneling and atomic force microscope (STM/AFM) as well as by on-surface annealing. The structure of the generated acenes has been visualized by high resolution non-contact AFM imaging and the evolution of the transport gap with the increase of the number of fused benzene rings has been determined on the basis of scanning tunneling spectroscopy (STS) measurements. PMID- 29791083 TI - Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase. AB - Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives. PMID- 29791085 TI - Sulfonylation of Benzylic C-H Bonds through the Reaction of Aryl(o tolyl)methanones with Sulfonyl Hydrazides or Sulfonyl Chlorides. AB - A sulfonylation of benzylic C-H bonds of aryl(o-tolyl)methanones with arylsulfonyl hydrazides or arylsulfonyl chlorides has been developed. Arylsulfonyl hydrazides and arylsulfonyl chlorides were employed as sulfonylating reagents respectively to complete this transformation. During the reaction, enols were generated in situ from aryl(o-tolyl)methanones under UV irradiation, and subsequently reacted with sulfonyl radicals to provide a range of aryl(2 (arylsulfonylmethyl)aryl)methanones. PMID- 29791084 TI - The Hospital Readmissions Reduction Program-learning from failure of a healthcare policy. AB - Heart failure is the leading cause of readmissions in patients aged >=65 years with high associated societal and economic costs. The utilization metric of 30 day risk standardized readmission rates (RSRRs) has therefore become a target to reduce healthcare costs. In this review, we discuss in detail the implementation, effectiveness, and unintended consequences of the Hospital Readmissions Reduction Program (HRRP)-the major healthcare policy approach in the U.S. to reduce readmissions by financially penalizing hospitals with higher than average 30-day RSRRs. The HRRP was enacted by the Patient Protection and Affordable Care Act of 2010 (popularly known as 'Obamacare'). The public reporting of RSRRs began in June 2009 and the HRRP readmission penalties went into effect starting fiscal year 2013. The policy had limited success in achieving its primary objective of reducing readmissions as the achieved reduction in heart failure readmissions was much smaller (~9%) than anticipated (~25%) with some of the reduction in RSRRs attributable to the artifact of administrative upcoding post-HRRP rather than an actual decline in readmissions. From the time of passage of this law, there have been significant concerns regarding gaming of the system such as increase in observation stays, delaying readmissions beyond discharge day 30, and inappropriate triage strategies in emergency departments in order to achieve lower readmission rates to avoid penalties. A series of independent reports have now suggested that implementation of the HRRP was associated with an increase in 30-day, 90-day, and 1-year risk-adjusted heart failure mortality in the U.S. with reversal in decade long trend of declining heart failure mortality. We review the evidence behind effect of the HRRP on readmissions and mortality outcomes as well as discuss various lessons to be learned from the design, implementation, and consequences of this policy. PMID- 29791086 TI - Modular In Situ Functionalization Strategy: Multicomponent Polymerization by Palladium/Norbornene Cooperative Catalysis. AB - Herein, we report a cooperatively palladium/norbornene-catalyzed polymerization, which simplifies the synthesis of functional aromatic polymers, including conjugated polymers. Specifically, an A2 B2 C-type multicomponent polymerization that is based on an ortho amination/ipso alkynylation reaction was developed for the preparation of various amine-functionalized arylacetylene-containing polymers. Within a single catalytic cycle, the amine side chains are site selectively installed in situ by C-H activation during the polymerization process, which represents a major difference from conventional cross-coupling polymerizations. This "in situ functionalization" strategy enables the modular incorporation of functional side chains starting from simple monomers, thereby conveniently affording a diverse range of functional polymers. PMID- 29791087 TI - Sexual and somatic development of wood frog tadpoles along a thermal gradient. AB - All amphibian species are known to have genetic sex determination. However, a variety of environmental conditions can moderate sexual differentiation, in some cases leading to sex reversal and skewed sex ratios. While there has been a recent focus on chemically-induced sex reversal in amphibians, temperature can also influence sexual differentiation. Building upon a classic 1929 study by Emil Witschi, we assessed temperature-mediated sex reversal. Witschi found that the wood frog sex ratio is 100% male at a high temperature (32 degrees C) compared to a 50:50 sex ratio at 20 degrees C. This pattern is consistent with multiple models of environmentally mediated sexual differentiation in vertebrates. To better understand thermally mediated sex reversal, we raised wood frogs at temperature increments of ~1 degrees C between 19 and 34 degrees C. Mirroring earlier findings, wood frog metamorph sex ratios are indistinguishable from 50:50 at the lowest temperature and entirely male at the highest temperatures. In between, sex ratios become increasingly male-dominated as temperatures increase, implying a steadily increasing tendency toward female-to-male sex reversal in warmer environments. There was no evidence of a threshold temperature effect on reversal patterns. We also show that, compared to males, females metamorphose larger and later in cooler conditions but earlier and smaller under warmer conditions. While the ecological relevance in this species is unknown, these results conform to the Charnov-Bull model of sex determination (in which female to-male sex reversal can increase fitness to genetic females at higher temperatures), suggesting the system would reward further study. PMID- 29791088 TI - Healthcare Costs and Utilization Project (HCUP): Opportunities to Improve Mental Health Care in Alabama. PMID- 29791089 TI - Making Care Transitions Safer: The Pivotal Role of Nurses. PMID- 29791090 TI - Electronic Nicotine Delivery Systems: Are You Prepared to Have a Conversation With Your Patients? PMID- 29791091 TI - Nurses Lead in Fighting Opioid Crisis. PMID- 29791092 TI - Is It Against the Law for Any Nurse Other Than Public Health Nurses to Fill Patients' Weekly Medication Containers. PMID- 29791094 TI - Copperhead Snake Bites. PMID- 29791093 TI - Nurse-Managed Clinic Paves the Way for an Interprofessional Student-Run Free Clinic. PMID- 29791096 TI - [MODULATION OF LACTATE PRODUCTION, TRANSPORT AND RECEPTION BY CELLS IN THE MODEL OF BRAIN NEUROVASCUL. UNIT I.] AB - Metabolic activity of cells within a neurovascular unit is among the factors determining structural and functional integritY of the blood-brain barrier and the an- giogenesis process. in order to verify the hypothesis about the role Of g1YcolYtic activity in the perivascula astroglialcells associated with lactate release in the development of functioning of cerebral microvessel endothelial cells, we have used a three-component model of the brain neurovascular unit in vitro. The cells o f n o n -en d o th elia l o rig in w ere in c u b a te d in th e p rese n ce o f m o d u la to rs o f la c ta te pro d u c n ago ni glu c ose ta a G ly c o s o) , bas t h e oe t a n t a at- blocker of monocarboxylate transporters MCTlprCT and recepltiors of3Ctate0produasan (2-donisyoflactate G e8 breceptor) Iasa estbishe vthat that te suppression of lactate production and transport, prdc o1,adrcpin(C-O-Aa n (2gdoxysgflucoase as a glycolysis inhibitor), transport (phloretin as a sukr of lacaroduto transport , aswellasastimultionof3lactate receptors in astroglial cells, lead to aberrant development of endothelial layer, ther by u g g e tin t h efor atio o f anti ngi gencmi roen ircm ent for cerebral endothelium due to inappropriate lactate-m ediated effects. KeYw.ords:-n-eur-ovascular unit; metabolism; glYcolysis; lactate. PMID- 29791095 TI - [COMPARATIVE STUDY OF THE INFLUENCE OF BENZIMIDAZOLE DERIVATIVE RU-1205, DIAZEPAM, AND SODIUM VALPROATE ON THE SEIZURE THRESHOLD, ANTICONVULSANT TOLERANCE, AND REBOUND EFFECTS.] AB - We have studied the effects of acute administration of benzimidazole derivative RU-1205 (9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo(1,2-alpha)benzi- midazole), diazepam, and sodium valproate on the threshold for myoclonic and clonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ) in mice. Furthermore, the effects of chronic administrations of RU-1205 and diazepam on the development of anticonvulsant tolerance and rebound phenomena were evaluated. The TID50 values (the dose of anticonvulsant required to increase the PTZ seizure threshold by 50%) of RU-1205, diazepam, and valproate for my- oclonic seizures were 7.9, 120.4, and 1.2 mg/kg (i.p.), respectively. TID50 of RU-1205, diazepam, and valproate for clonic seizures were 7.9, 116.9, and 1.3 mg/kg (i.p.), respectively The chronic administration of RU-1205 (31 mg/kg, i.p., 28 days) did not lead to the development of anticonvulsant tolerance or rebound effect after discontinuation of treatment. The anticonvulsant effect of diazepam (5 mg/kg, i.p., 28 days) in chronically treated mice was gradually abo- lished and the rebound effect was observed after the discontinuation of treatment. PMID- 29791098 TI - [INCREASING EFFICACY OF PREGRAVIDAR PREPARATION IN MARRIED COUPLES SUFFERING OF INCREASED RISK OF PREGNANCY MISCARRIAGE.] AB - This study was aimed at revealing clinical and laboratory peculiarities in the health of married couples suffering of pregnancy miscarriage and the possibility of correcting this state by preconception therapy with reamberin, based on analysis of the results of observations and investigations for 196 married couples. At the first stage, we have studied the influence of provoking factors on the miscarriage during first trimester, including the presence and degree of chronic nonspe- cific intoxication. The patients were divided into groups: first (main) group including 40 couples, in which the pregnancy was complicated by the risk of pre- gnancy termination in the first trimester and second (comparison) group of 74 couples, in which abortion in the first trimester was followed by complex precon- ception therapy. The control group included 82 couples with normal course of pregnancy in the first trimester. At the second stage, we have studied the efficacy of including reamberin in the scheme of therapy. For this purpose, patients in the second (comparison) group were separated into subgroups. In subgroup I, 50 male patients received reamberin (i.v., dropwise, 400 mL per day at a rate of 60 - 70 drops/min, over 10 days), while 24 male patients of subgroup II were treated according to commonly accepted schemes (involving recommendations concerning regime and diet, psychological aid, and polyvitamins in prophylac- tic doses). Analysis of the obtained data revealed the presence of nonspecific intoxication in patients of the main group comparison groups, which was related to the increased level of intermediate metabolism products and osmotic state of plasma, and disorders in the hepatobiliary system as manifested by hyperbiliru- binemia, increased level of transaminases, urea, creatinine, etc. In addition, most patients also exhibited changes in spermograms, including astenozospermia (75.9 ? 7.9%) and teratozospermia (69 ? 8.6%) on the background of relative androgenous insufficiency, and bacterospermia in 26.7 ? 8.1% of patients from couples where the pregnancy of females was complicated by risk of miscarriage in the first trimester, and in 34.3 ? 5.8% of patients from couples receiving re- habilitation care upon abortion in the first trimester. The inclusion of reamberin in the scheme of complex preconception therapy of male in pairs with miscarri- age problems increased the efficacy of therapy. This was manifested by decrease in the parameters of intoxication (on the average by 21 % (d = 0.017), positive dynamics of the main indices of spermograms, and improvement of the general state, which led in turn to increased probability of the onset and maintenance of pregnancy. PMID- 29791097 TI - [EFFECT OF CAPTOPRIL ON THE ARTERIAL PRESSURE AND RHEOLOGICAL PROPERTIES OF BLOOD, THE VASODILATOR ACTIVITY OF ENDOTHELIUM, AND RELATIONSHIP OF THESE INDICES IN SHR RATS.] AB - Prevention of cardiovascular complications is one of the objectives of antihyperiensive therapy. However, the expected effect cannot be fully achieved by me- ans of the blood pressure control only. The authors studied the effect of captopril administration in SHR rats by monitoring the following parameters: arterial blood pressure, rheological properties of blood, and endothelial index of vasodilator activity (IVA), as well as their correlations. In SHR rats, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher by 28 - 33% as compared to WKY rats. In comparison to normotensive animals, the blood vis- cosity (BV) at shear rates from 30 to 450 sec -1 in SHR rats was increased by 12 - 15% (p = 0.020), the aggregation of red blood cells was increased by 22% (p = 0.012), and their plasticity in the range of shear stresses within 3 - 20 Pa was decreased by 2 - 8% (p = 0.028). The IVA value in SHR rats was lower by 26 % (p = 0.030) than that in WKY rats. The administration of captopril decreased the SBP and DBP values down to the level in normotensive animals, but did not influence the rheological properties of blood and its IVA value. In WKY rats, the BV exhibited reliable correlation with IVA (with r from +0.60 ai +0.67, p <0.05) at shear rates ranging within 30 - 450 sec -1, while the rheological parameters were correlated with neither SBP nor DBP. In SHR rats, the BV corre- lated with IVA only at 450 sec -1 (with r =+0.50, p = 0.025), and there were relationships between SBP and BV (r = + 0.64, p = 0.008) and the aggregation in- dex (r = +0.69, p = 0.003). Rats treated with captopril showed no correlations between hemorheological and hemodynamic parameters. Therefore, captopril decreases the arterial blood pressure, but it also violates the contour of vascular tone regulation associated with changes in shear stress on the vascular wall, which plays an important role in ensuring adequate local blood flow. PMID- 29791099 TI - [ANTIOXIDANT AND CYTOPROTECTOR PROPERTIES OF GENISTEIN - ISOFLAVONE WITH ESTROGENIC ACTIVITY.] AB - Phytoestrogen genistein can exhibit cytoprotective and antioxidant properties, providing chemopreventive action, and produce cytotoxic effects on some tu- mors. In this work, the cytotoxic, cytoprotective, and antioxidant properties of genistein have been studied on model tumor cells (human cervical cancer HeLa cells) and normal cells (rat dermal fibroblasts, RDF). For assessing the cytotoxic effect of genistein (spectrophotometric MTT assay), the reference drug was cis-diaminodichloroplatinum (cisplatin); for evaluating antioxidant action, beta-estradiol was the reference drug. It is established that genistein produces a cyto- toxic effect only at high concentrations, IC50 = 20 mM and 14 mM for RDF and HeLa cells, respectively, which is 30 and 10 times higher than IC50 for cisplatin on these cells. Genistein like estradiol, but unlike cisplatin, had no effect on the mitochondrial pore induction from rat liver mitochondria. Thus, genistein at physiological concentrations (up to 200 n) acts as a cytoprotective agent. High antioxidant activity of genistein also suggests the possibility of its use as a chemopreventive drug. PMID- 29791101 TI - [SPECIFIC FEATURES AND PROSPECTS OF THE PHARMACOKINETIC STUDY OF HISTOCHROME.] AB - The review summarizes available data on the pharmacokinetics of new Russian drug histochrome, the active substance in which is a quinoid pigment of marine invertebrates, echinochrome A (2,3,5,6,8-pentahydroxy-7-ethyl-1,4 naphthoquinone). Based on the modem notions about close connection of the pharmacoki- netics and pharmacodynamics of drugs, the authors consider prospects for studying the histochrome pharmacokinetics, including the issues of echinochrome A metabolism and the probability of formation of a biologically active metabolite. In assessing the pharmacokinetic aspects of the new drug, the authors draw at- tention of researchers to profound study of histochrome administration schemes and dosing regime in the context of improving its therapeutic applications. PMID- 29791100 TI - [EXPERIMENTAL MODELS OF ALCOHOLIC NEUROPATHY IN RATS.] AB - The aim of this work was to study the behavioral and histopathomorphological signs of peripheral neuropathy development in male Wistar rats on the model of alcoholic neuropathy. Chronic consumption of ethanol solution with concentration increasing from 7.47 to 26.2% (w/w) resulted in neuropathy (allodynia) de- velopment after 8 weeks of chronic alcohol administration. The behavioral signs of allodynia became significant on the 8th week and were retained up to the end of experiment (15 weeks of ethanol administration). The reference drug gabapentin effectively reduced the manifestation of allodinia. Histological exami- nation of sciatic nerve preparations from animals killed after ethanol consumption for 5, 10 and 15 weeks revealed the development of histopathomorphological pattern with increasing duration of chronic alcoholization. At the initial stage, the morphological basis of observed behavioral manifestations was provided by excess lipid deposition in peri/epineurium of nerve specimens). The further increase in treatment duration (up to 10 and 15 weeks) was associated with demye- lination and development of inflammation of the sciatic nerve. This experimental model allows one to investigate the efficacy of new neuroprotective and ana- lgesic substances - potential drugs for both prevention and management of neuropathy. PMID- 29791102 TI - [STUDYING ANXIOLYTIC AND ANTIDEPRESSANT PROPERTIES OF 2,2,6,6 TETRAMETHYLPIPERIDONE DERIVATIVE.] AB - Neuropharmacological properties of LK-998 (3,4,5-trimethoxy-N'-(2,2,6,6 tetramethylpiperidin-4-yliden)benzohydrazide), a 2,2,6,6-tetramethylpiperidone de rivative have been studied. LK-998 exhibited anxiolytic activity in doses of 10 and 20 mg/kg, significantly increasing the duration of animal staying of in open arms of the elevated plus maze as well as the number of arm entries. The efficiency of drug tested in a dose of 10 mg/kg was comparable with that of afobazole in a dose of 5 mg/kg. In marble burying test, it was also found that animals treated with LK-998 at 10 mg/kg buried a close number of balls to that as rodents treated with afobazole at 5 mg/kg. At the same time, LK-998 in doses 10 and 20 mg/kg did not produce any antidepressant action in the learned helplessness test. Thus, LK-998 in a dose of 10 mg/kg has anxiolytic and anticompulsive effects comparable to those of afobazole at a dose of 5 mg/kg. The study of potenti- al side effects of LK- 998 in a dose of 200 mg/kg (i.e., 20 times the therapeutic dose of 10 mg/kg) showed that the drug tested caused neither side effects nor symptoms of neurological deficiency within 24 hours and on longer terms (4, 10 and 14 days after administration). PMID- 29791103 TI - [ANALGESIC ACTIVITY OF SOME NEW DECAHYDROQUINOLINE DERIVATIVES.] AB - The work was aimed at assessing in vivo the analgesic properties of ten decahydroquinoline derivatives (pharmacologically active substances, PAS) and deter- mining the role of opioid receptors in mechanism of their action. Among the derivatives studied, pronounced analgesic properties at a dose of 1/4 LD50 was ob- served for two compounds (PAS-70 and PAS-71), while four compounds (PAS 66, PAS-69, PAS-74, PAS-76) produced weak and short anesthetic effects. PAS-70 and PAS-71 showed analgesic action even in a dose of 1/8 LD50. The maximum effect of PAS-70 and PAS-71 was developed within 20 - 60 min after administration and lasted for two hours (PAS-70 in a dose of 1/4 LD50, PAS-71 in doses of 1/4 and 1/8 LD50). The analgesic effect of PAS-70 (at 1/4 LD5,) and PAS-71 (at 1/4 and 1/8 LD50) significantly exceeds that of reference drugs metamizol (1/4 LD5) and ketorolac (1/4 LD50). The mechanism of drug action is not related to opioid receptors. PMID- 29791104 TI - [EFFECT OF FLIXOTIDE ON ELECTRON-MICROSCOPIC CHANGES IN LUNG TISSUE OF GUINEA PIGS WITH BRONCHIAL ASTHMA MODEL.] AB - Chronic experiments on nonlinear short-hair guinea pigs with bronchial asthma model caused by administration of ovalbumin without treatment showed the ap- pearance of electron-microscopic changes of the lungs tissue in the form of chronic allergic inflammation. Significant changes in air - blood barrier with a loo- sening of intercellular contacts, degenerative changes in alveolocytes, and circulatory disorders with symptoms of vascular dilatation and stasis of blood cor- puscles were revealed. Treatment with inhaled fluticasone propionate in the form of flixotide preparation (GlaxoSmithKline, UK) for 3 months (2 times a day for 30 - 45 sec) partially reduced disorders of circulation and transcapillary exchange, decreased edema and degenerative changes in the cells, and restored in- tercellular contacts and pinocytic activity of the air - blood barrier. The obtained results show the expediency of further studies for determining the optimal du- ration of basic treatment during remission of bronchial asthma. PMID- 29791105 TI - [NEW APPROACH TO COMPARING NSAID EFFICACY BY LONG-TERM MONITORING OF EXPERIMENTAL INFLAMMATION MODELS.] AB - Experiments on inflammatory edema modeling by sub-plantar injection of carrageenan lambda (1 %) and formalin (2 %) showed substantial differences betwe- en the two models during long-term observation, including irreversible damage caused by formalin (at reversible carrageenan action) and high intensity of for- malin edema (in contrast to carrageenan edema) in mice. We propose a new approach to evaluation of the so-called total inflammatory burden (experimental analog of disease outcome) by calculating the area under the inflammation intensity versus time curve. With the use of this approach, we showed the absence of any effect of conventional NSAIDs (naproxen, diclofenac. indomethacin) on the total inflammatory burden induced by carrageenan or formalin injections in mice and rat paw edema models. These results show the need for using new approaches in the search for potential anti-inflammatory agents. PMID- 29791106 TI - [EFFICACY OF ANTIARRHYTHMIC AGENTS UNDER CONDITIONS OF STIMULATION OF THE SYMPATHETIC NERVOUS SYSTEM.] AB - The problem of weakening of the action of antiarrhythmic drugs under conditions of activation of the sympathetic nervous system draws increasing attention of researchers. These conditions are frequently encountered in clinical practice in cases of ischemia, myocardial infarction, and in patients with sustained ventricular arrhythmia. In addition, sympathetic, hyperactivity is a characteristic feature of serious cardiovascular diseases including heart failure. The beta-adrenergic stimulation can significantly modulate the electrophysiological action of antiarrhythmic drugs. There are significant differences in the ability of antiarrhythmic drugs to retain efficacy on the background of sympathetic stimulation. Additional administration of beta-blockers to patients with ventricular tachycardia, cardiac insufficiency, cardiomyopathy and patients after myocardial infarction is highly effective and is worth of addition al investigation. The search for drugs whose effect is not affected by sympathetic stimulation is still topical. PMID- 29791107 TI - [PHARMACOGENETIC MARKERS OF THE EFFECTIVENESS OF TREATMENT OF CHILDREN WITH ATOPIC BRONCHIAL ASTHMA.] AB - Data on the pharmacogenetic markers of the effectiveness of treatment of children with atopic asthma are presented, which reveal a variability of the response to treatment with glucocorticosteroids, leukotriene receptor antagonists, and b2 adrenoreceptor agonists in children with bronchial asthma. The association of genotype Gly/Glyl6 gene b2-adrenergic receptor with insufficient effect of the therapy with short-acting b2-agonists is demonstrated. The Glyl6 allele, CYP2D6 - 1934GGd contributes to the formation of a phenotype with severe asthma and tolerance to therapy with b2-agonists and inhaled corticosteroids. PMID- 29791108 TI - [FOOD - DRUG INTERACTIONS: TYPES AND MECHANISMS.] AB - Types and mechanisms of drug - food interactions are described. The most frequently encountered interaction is of the pharmacokinetic type, by which food components change the absorption of drugs from the gastrointestinal tract and affect the biotransformation of drugs. The majority of such interactions is of cli- nical significance and must be taken into account in recommendations concerning methods of drug administration. PMID- 29791109 TI - [ASSESSMENT OF SPECIFIC PHARMACOLOGIC ACTIVITY OF UNIFUSOL ON ENDOTHELIUM DYSFUNCTION MODEL INDUCED BY N-NITRO-L-ARGININE METHYL ETHER.] AB - Specific pharmacologic activity of sodium-L-arginine succinate (unifusol) was studied on endothelium dysfunction model (EDM) in rats. EDM was induced by daily administration of N-nitro-L-arginine methyl ether (L-NAME). The effectiveness of experimental therapy with unifusol was assessed by changes in the arterial pressure level, duration of endothelium-dependent and -independent vasodilation, and the blood concentration of endothelial dysfunction markers including VEGF, NO, endothelin-I and the number of desquamated endotheliocytes. Administration of unifusol favors correction of blood vessel endothelium state manifested by normalization of its functional activity and reduction of the apoptosis of endotheliocytes. In addition, the obtained results unambiguously confirm considerable vasodilating and antihypertensive effects of unifusol. PMID- 29791110 TI - [National and international aspects of the medico-legal examination of injured witnesses and defendants in criminal proceedings]. AB - Depending on the type of offence, the medico-legal examination of victims of violence for the purpose of collecting evidence in criminal proceedings requires prompt physical examination of the victim, the exact description and, wherever possible, photographic documentation of the injuries and their forensically correct interpretation. Examination, documentation and assessment have to meet minimum standards. In addition it must be ensured that the examiner or expert has an independent organisational, administrative and financial status. An independent expert must not be an organisational part of the police force, the public prosecution and the court. Legal regulations have to make sure that the expert cannot be influenced "through official channels". His or her financial independence must make attempted bribery at least improbable. The independence of the expert is particularly important, if persons become victims of violence while they are under the custody of the state, especially the police, in prisons and after compulsory commitment to a psychiatric hospital. PMID- 29791111 TI - [Matching bite marks using modeling wax plates]. AB - Bite marks are rarely seen in forensic medical examinations. In most cases one can easily differentiate whether a bite mark is of human or animal origin due to the arched shape and crushed character of human bite marks. From a forensic point of view it is more interesting whether a dental imprint has been caused by an adult or a child, because children are often abused for a defensive statement. Two cases of bite injuries in children are presented. In the first case, a two month-old infant was presented by pediatricians. The second case deals with a one year-old boy who had allegedly been bitten several times by a two-year-old girl in a nursery school. A comparison could be performed between the bite mark impressions on the victim's skin (based on photographic documentation) and dental imprints of single teeth measuring the tooth width on the one hand and the intercanine distance on the other hand with the help of modeling wax plates. This procedure showed good correlations between the bite marks on the victim and the dental status of the biter. Especially for taking bite impressions on children, modeling wax plates are a simple, fast and cheap alternative to dental impression taking. PMID- 29791112 TI - [Drinking study on the pharmacokinetics of the grappa congener 2-butanol]. AB - A drinking study on the pharmacokinetics of the typical grappa congeners 2 butanol and 2-butanone (methyl ethyl ketone) was performed. It was expected that the concentration ratio might provide a means to estimate the time of ingestion of a grappa beverage. Twelve subjects drank a volume of the grappa "Vecchio di Prosecco" (42 vol%) to reach a blood alcohollevel of 1.20 %o. In the congener analyses in serum, a median 2-butanol concentration of 0.79 mg/1 (range 0.45-1.34 mg/1) and of 1.01 mg/I (0.44-1.62 mg/1) for 2-butanone were measured. The concentration-time curve was biphasic starting with a slow and plateau-like elimination. However, considerable inter-individual differences were observed. Only in 3 subjects, a 2-butanol : 2-butanone ratio below 1 suggested ingestion within the last 6 hours. The majority of the subjects exhibited higher concentrations of 2-butanone than of 2-butanol such that the ratio was always smaller than 1. According to the present results the concentrations of 2-butanol and 2-butanone or their ratio do not provide a reliable basis to draw conclusions on the time of grappa ingestion. PMID- 29791113 TI - [Rare causes of iatrogenic pericardial tamponade - 2 case reports]. AB - Two rare causes of iatrogenic pericardial effusions are presented. In the first case, a 61-year-old woman who had undergone laparoscopic surgery for a diaphragmatic hernia was resuscitated without success the next day. As cause of death circulatory failure as a result of post-operative pulmonary embolism was reported. Autopsy results showed that the pericardium and the heart had been sewn to the diaphragm. The suture was torn from the tissue, which caused a hemorrhage into the pericardium and the chest cavity, so that death was diagnosed to be due to cardiac tamponade and hemothorax after an iatrogenic heart injury. In the second case, a 62-year-old man who had developed a massive incisional hernia after treatment of an abdominal gunshot wound underwent open herniotomy with mesh repair. Postoperatively, the man complained about increasing pain and shortness of breath. He was transferred to another hospital for further assessment, where a cardiac tamponade was diagnosed. Autopsy results showed that three of the plastic staples used to fix the mesh had perforated the diaphragm and the pericardium thus injuring the adjacent right ventricle with subsequent perforation and development of a hemopericardium. PMID- 29791114 TI - [Stature estimation from teeth and jaw]. AB - After the discovery of skeletonized human remains, the estimation of stature is an important element of the so-called "biological profile". Typically, long bone lengths are used in regression formulas. If long bones are not available, predictions of stature cannot be made. Human skulls are often the subject of forensic osteological examination, sometimes even detached. Therefore, it seems reasonable to search for skull measurements that have a sufficiently good correlation to stature. The aim of the study presented was to measure odonto stomatological parameters using post-mortem CT data to check whether the esti- mation of stature was possible on this basis. Three classic tooth dimensions (MD, BL, ZL), two diagonal tooth dimensions (MBDL, DBML) first described by Lund and Mornstad in 1999, two tooth dimensions defined for the first time in this study (MKDO, DKMO), the mesiodistal index (MDS) and also the palatal arch dimensions (arch length, arch width, molar length and dental length) - each at maxilla and mandible - were digitally measured on a total of 799 teeth of 48 virtual 3-D reconstructed skulls (33 males and 15 females). For most of the aforementioned measurements no statistically significant relation to stature was found. There were positive correlations by Pearson at a significance level of 99 % (2-sided) at three measurements: ZL 15, MKDO 14 and MKDO 15. Positive correlations by Pearson at a significance level of 95 % (2-sided) could be determined for eight measurements, but an applicable regression formula could not be calculated for any of the parameters. Despite a statistical correlation of a few teeth parameters with body length, they must be considered unsuitable for estimating stature. PMID- 29791115 TI - [A case of acrania?]. AB - The article reports on the case of a premature and stillborn child. As a first step it had to be clarified whether the child had been alive. The pathological examination of the placenta performed after autopsy could prove a retroplacental hematoma as the cause of death. Furthermore the autopsy revealed a severe skull deformity that would probably have made the survival of the child impossible. PMID- 29791116 TI - Identification of novel alternative splicing variants within swine Setd8 gene and their high mRNA expression in testis. AB - SET domain containing (lysine methyltransferase) 8 (Setd8), a histone modification enzyme, affects cell cycling, chromosome condensation, high efficient repair of DNA double strand breaks and so on. The objective of this study was to identify novel alternative splicing variants of pig Setd8 gene and its mRNA expression. Four 180-day-old male Guanzhong Black (GZB) pigs and six male Landrace piglets (including three 30-day-old and three 7-day-old pigs) were collected to study Setd8 gene. Herein, two novel variants, Setd8a and Setd8b, were found in pig. The entire sequences of Setd8a and Setd8b variants were 1,039 bp and 958 bp, respectively. qRT-PCR results showed that Setd8a and Setd8b were highly expressed in brains and testes of 180-day-old GZB pigs. Moreover, the expressions of the two Setd8 variants were significantly higher in testis than brain of GZB pig (P < 0.05). Further study on testis showed that the mRNA expression of Setd8a variant was significantly lower than Setd8b variant in 30 day-old and 7-day-old pigs (P < 0.05). The mRNA expression of Setd8a variant'was lower than Setd8b variant in GZB pigs (P > 0.05). Moreover, the expressions of the two Setd8 variants were significantly higher along with age enlargement. In conclusion, Setd8a and Setd8b were firstly identified in pigs and both were expressed in pig testis. Setd8b was the major splicing variant of pig Seid8 gene transcript product. Moreover, the expressions of Setd8 variants were time dependent. All these findings would enrich the study of Setd8 gene in pig testis. PMID- 29791117 TI - Anti-neoplastic effects of topoisomerase inhibitors in canine mammary carcinoma, melanoma, and osteosarcoma cell lines. AB - Numerous topoisomerase inhibitors with proven efficacy have been used extensively to treat various human neoplasms. However, among these, only doxorubicin has been used and studied extensively in veterinary oncology. The current study was performed to evaluate the responsiveness of canine osteosarcoma (cOSA), mammary gland tumour (cMGT), and malignant melanoma (cMM) cell lines to several topoisomerase inhibitors. In addition, the correlation between the sensitivity to treatment and multi-drug resistant (MDR) factors was investigated. cOSA cell lines exhibited higher sensitivity than cMGT and cMM cell lines to all the topoisomerase inhibitors tested in vitro; this was associated with the levels of multi-drug resistance protein 1 (MDR1) gene expression in the cOSA cell lines. Treatment of cOSA (HMPOS) and cMGT cell line (CHMp) xenograft mouse models with etoposide markedly delayed tumour progression in HMPOS xenografts, but failed to elicit lasting anti-tumour effects on CHMp xenograft mice. The present findings suggest that MDR1 represents a molecular signature for prediction of treatment efficacy of topoisomerase inhibitors, especially that of etoposide, which may be a clinically useful anti-tumour agent for cOSA; however, further study is necessary to refine the treatment protocol. PMID- 29791118 TI - Particle-Induced X-ray Emission Analysis of Zierum Trace and Major Elements in Cattle with Acute Coliform Mastitis. AB - The aim of the present study was to examine the applicability of the direct determination of trace and major element concentrations in serum samples collected from Holstein dairy cattle with acute coliform mastitis (n = 53) compared with a healthy control group (n = 39). Twenty-eight elements (Na, Mg, Al, Si, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ce, Ni, Cu, Zn, Ga, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, and Pb) were detected by particle-induced X-ray emission (PIXE). Significant differences were observed in serum K, Fe, Zn, and Br concentrations, but not in those of the remaining twenty-four elements. Furthermore, serum Fe concentrations (0.751 +/- 0.583 MUg/ml, n = 18) were significantly lower in dairy cattle with a poor prognosis than in those with a good prognosis (0.945 +/- 0.393 MUg/ml, n = 35, P < 0.05) and healthy controls (1.458 +/- 0.391 MUg/ml, n = 39, P < 0.01). We proposed a diagnostic cut-off point for serum Fe concentrations of <0.82 MUg/ml based on receiver operating characteristic (ROC) curves in order to identify cattle with a poor prognosis. The results of the present study indicated that assessing the elemental composition of serum, particularly iron, is a promising prognostic tool for determining the outcomes of cattle with severe acute coliform mastitis. PMID- 29791119 TI - Antibody detection from Middendorf's vole (Microtus middendorffii) against Tula virus captured in Mongolia. AB - Mongolia in 2010 and 2011. A total of 76 voles belonging to the genera Myodes and Microtus were captured. Most of the voles that were seropositive to Tula virus antigen were Middendorf's voles (Microtus middendorffii (6/31)). Two of the 18 Myodes voles were also seropositive to Tula virus antigen. On the other hand, only one vole was seropositive to Puumala virus antigen. The results suggest that Tula virus was maintained in Middendorf's vole. This is the first report of detection of anti-Tula virus antibody in the central part of the Eurasia continent. PMID- 29791120 TI - Amenorative effects of exogenous gonadotropins on reproductive profiles of replacement gilts with delayed puberty in a farm in Thailand. AB - This study was to investigate the effect of gonadotropins on reproductive profiles of replacement gilts with delayed puberty. Totally, 136 Landrace X Yorkshire crossbred gilts, were categorized into control (n = 58) and treatment (n = 78) groups. Gonadotropins (400 U eCG plus 200 IU hCG) were administered in treatment group only. The results revealed that gilts in treatment group had higher number of gilts with estrus (92.3 vs 25.9%, P < 0.001), shorter onset to estrus (4.7 +/- 0.3 vs 9.0 +/- 0.8 d, P < 0.001), higher number of dominant follicles (18.0 +/- 0.2 vs 13.2 +/- 0.3 follicles, P < 0.001), and higher farrowing rate (87.5 vs 53.3%, P = 0.002) than those in control group. In conclusion, gonadotropins containing 400 IU eCG plus 200 IU hCG could improve reproductive profiles in replacement gilts with delayed puberty. PMID- 29791121 TI - Early and Midterm Results of the Arterial Switch Operation: A 9-Year, Single Center Experience. PMID- 29791122 TI - Daptomycin eosinophilic pneumonia: an adverse effect to be aware of. PMID- 29791123 TI - [Candida parapsilosis infection in a corneal transplant patient]. PMID- 29791124 TI - [Unusual Gram-negative bacteria as etiologic agents of nosocomial infections in a Neonatal Intensive Care Unit]. PMID- 29791125 TI - Pregnancies in perinatally HIV-infected women: antiretroviral treatment strategies, obstetric and virologic outcomes. PMID- 29791126 TI - A case of otitis externa caused by non-01/non-0139 Vibrio cholerae after exposure at a Mediterranean bathing site. PMID- 29791127 TI - What to know before raising a research question? AB - With the purpose of establishing a research question adequately, it is necessary to update the state of knowledge in scientific publications, in order to verify the originality of the hypothesis; for this it is necessary to have acquired the training that allows to read and adequately criticize the methodology and the analysis of the medical literature. PMID- 29791128 TI - Donor-Acceptor Supramolecular Organic Nanofibers as Visible-Light Photoelectrocatalysts for Hydrogen Production. AB - Perylene tetracarboxylic diimide (PTCDI) derivatives have been extensively studied for one-dimensional (1D) self-assembled systems and for applications in photocatalysis. Herein, we constructed a PTCDI-based donor-acceptor (D-A) supramolecular system via in situ self-assembly on an indium tin oxide conductive glass surface. The self-assembled PTCDI nanostructures exhibit well-defined nanofibril morphologies and strong photocurrents. Interestingly, a strong and reversible electrochromic color change was observed during cyclic voltammetry. The color of the nanofibers changed from red to blue and then to violet as the reduction progressed to the radical anion and then to the dianion. This series of one-electron reductions was confirmed by UV absorption, electron paramagnetic resonance spectroscopy, and hydrazine reduction. Most importantly, these PTCDI nanofibers exhibit efficient photoelectrocatalytic hydrogen production with remarkable stability under xenon lamp illumination (lambda >= 420 nm). Among the three nanofibers prepared, the fibers assembled from PTCDI molecule 2 were found to be the most effective catalyst with 30% Faradaic efficiency. In addition, the nanofibers produced hydrogen at a steady-state for more than 8 h and produced repeatable results in 3 consecutive testing cycles, giving them great potential for practical industrial applications. Under an applied bias voltage, the 1D intermolecular stacking along the long axis of the nanofibers affords efficient separation and migration of photogenerated charge carriers, which play a crucial role in the photoelectrocatalytic process. As a proof-of-concept, the D-A structured PTCDI nanofibers presented herein may guide future research on photoelectrocatalysis based on self-assembled supramolecular systems by providing more options for material design of the catalysts to achieve greater efficiencies. PMID- 29791129 TI - Formation of Deep Electron Traps by Yb3+ Codoping Leads to Super-Long Persistent Luminescence in Ce3+-Doped Yttrium Aluminum Gallium Garnet Phosphors. AB - The Y3Al2Ga3O12:Ce3+-Cr3+ compound is one of the brightest persistent phosphors, but its persistent luminescence duration is not so long because of the relatively shallow Cr3+ electron trap. To compare the vacuum referred binding energy of the electron trapping state by Cr3+ and lanthanide ions, we selected Yb3+ as a deeper electron trapping center. The Y3Al2Ga3O12:Ce3+-Yb3+ phosphors show Ce3+:5d -> 4f green persistent luminescence after blue light excitation. The formation of Yb2+ was confirmed by the increased intensity of absorption due to Yb2+:4f-5d at 585 nm during the charging process. This result indicates that the Yb3+ ions act as electron traps by capturing an electron. From the thermoluminescence glow curves, it was found that the Yb3+ trap makes a much deeper electron trap with a 1.01 eV depth than the Cr3+ electron trap with a 0.81 eV depth. This deeper Yb3+ trap provides a much slower detrapping rate of filled electron traps than the Cr3+ codoped persistent phosphor. In addition, by preparing transparent ceramics and optimizing Ce3+ and Yb3+ concentrations, the Y3Al2Ga3O12:Ce3+(0.2%)-Yb3+(0.1%) as made transparent ceramic phosphor showed super-long persistent luminescence for over 138.8 h after blue light charging. PMID- 29791130 TI - Quantification of Serum High Mobility Group Box 1 by Liquid Chromatography/High Resolution Mass Spectrometry: Implications for Its Role in Immunity, Inflammation, and Cancer. AB - High mobility group box 1 (HMGB1) is a non-histone chromosomal protein, which can be secreted through a variety of pathways and bind to pattern recognition receptors to release pro-inflammatory cytokines. Previous studies have suggested that HMGB1 is upregulated in numerous inflammatory diseases and that it could be a biomarker for such diseases. However, these studies used immunoassay-based methods to analyze serum HMGB1. Autoantibodies to HMGB1 in serum are found in healthy control subjects as well as in patients with different diseases. HMGB1 also binds to haptoglobin, a highly abundant plasma protein. This means that antibodies used in immunoassays must compete with binding of HMGB1 to endogenous serum HMGB1 autoantibodies and haptoglobin. To overcome these potential problems, we developed and validated a specific and sensitive assay based on stable isotope dilution and immunopurification to quantify HMGB1 in plasma and serum using two dimensional nano-ultra-high-performance liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry. Using this assay, we found that serum HMGB1 in 24 healthy control subjects (6.0 +/- 2.1 ng/mL) was above the mean concentration reported for 18 different diseases (5.4 +/- 2.8 ng/mL) where the analyses were conducted with immunoassay methodology. In light of our finding, the role of HMGB1 in these diseases will have to be re-evaluated. The concentration of HMGB1 in citrated and EDTA-treated plasma from the same healthy control subjects was below the limit of detection of our assay (1 ng/mL), confirming that HMGB1 in serum arises when blood is allowed to clot. This means that future studies on the role of HMGB1 in vivo should be conducted on plasma rather than serum. PMID- 29791131 TI - Sensitivity Enhancement of Forster Resonance Energy Transfer Immunoassays by Multiple Antibody Conjugation on Quantum Dots. AB - Quantum dots (QDs) are not only advantageous for color-tuning, improved brightness, and high stability, but their nanoparticle surfaces also allow for the attachment of many biomolecules. Because IgG antibodies (AB) are in the same size range of biocompatible QDs and the AB orientation after conjugation to the QD is often random, it is difficult to predict if few or many AB per QD will lead to an efficient AB-QD conjugate. This is particularly true for homogeneous Forster resonance energy transfer (FRET) sandwich immunoassays, for which the AB on the QD must bind a biomarker that needs to bind a second AB-FRET-conjugate. Here, we investigate the performance of Tb-to-QD FRET immunoassays against total prostate specific antigen (TPSA) by changing the number of AB per QD while leaving all the other assay components unchanged. We first characterize the AB-QD conjugation by various spectroscopic, microscopic, and chromatographic techniques and then quantify the TPSA immunoassay performance regarding sensitivity, limit of detection, and dynamic range. Our results show that an increasing conjugation ratio leads to significantly enhanced FRET immunoassays. These findings will be highly important for developing QD-based immunoassays in which the concentrations of both AB and QDs can significantly influence the assay performance. PMID- 29791132 TI - Perturbation Theory/Machine Learning Model of ChEMBL Data for Dopamine Targets: Docking, Synthesis, and Assay of New l-Prolyl-l-leucyl-glycinamide Peptidomimetics. AB - Predicting drug-protein interactions (DPIs) for target proteins involved in dopamine pathways is a very important goal in medicinal chemistry. We can tackle this problem using Molecular Docking or Machine Learning (ML) models for one specific protein. Unfortunately, these models fail to account for large and complex big data sets of preclinical assays reported in public databases. This includes multiple conditions of assays, such as different experimental parameters, biological assays, target proteins, cell lines, organism of the target, or organism of assay. On the other hand, perturbation theory (PT) models allow us to predict the properties of a query compound or molecular system in experimental assays with multiple boundary conditions based on a previously known case of reference. In this work, we report the first PTML (PT + ML) study of a large ChEMBL data set of preclinical assays of compounds targeting dopamine pathway proteins. The best PTML model found predicts 50000 cases with accuracy of 70-91% in training and external validation series. We also compared the linear PTML model with alternative PTML models trained with multiple nonlinear methods (artificial neural network (ANN), Random Forest, Deep Learning, etc.). Some of the nonlinear methods outperform the linear model but at the cost of a notable increment of the complexity of the model. We illustrated the practical use of the new model with a proof-of-concept theoretical-experimental study. We reported for the first time the organic synthesis, chemical characterization, and pharmacological assay of a new series of l-prolyl-l-leucyl-glycinamide (PLG) peptidomimetic compounds. In addition, we performed a molecular docking study for some of these compounds with the software Vina AutoDock. The work ends with a PTML model predictive study of the outcomes of the new compounds in a large number of assays. Therefore, this study offers a new computational methodology for predicting the outcome for any compound in new assays. This PTML method focuses on the prediction with a simple linear model of multiple pharmacological parameters (IC50, EC50, Ki, etc.) for compounds in assays involving different cell lines used, organisms of the protein target, or organism of assay for proteins in the dopamine pathway. PMID- 29791133 TI - Design, Construction, and Validation of Histone-Binding Effectors in Vitro and in Cells. AB - Chromatin is a system of nuclear proteins and nucleic acids that plays a pivotal role in gene expression and cell behavior and is therefore the subject of intense study for cell development and cancer research. Biochemistry, crystallography, and reverse genetics have elucidated the macromolecular interactions that drive chromatin regulation. One of the central mechanisms is the recognition of post translational modifications (PTMs) on histone proteins by a family of nuclear proteins known as "readers". This knowledge has launched a wave of activity around the rational design of proteins that interact with histone PTMs. Useful molecular tools have emerged from this work, enabling researchers to probe and manipulate chromatin states in live cells. Chromatin-based proteins represent a vast design space that remains underexplored. Therefore, we have developed a rapid prototyping platform to identify engineered fusion proteins that bind histone PTMs in vitro and regulate genes near the same histone PTMs in living cells. We have used our system to build gene activators with strong avidity for the gene silencing-associated histone PTM H3K27me3. Here, we describe procedures and data for cell-free production of fluorescently tagged fusion proteins, enzyme linked immunosorbent assay-based measurement of histone PTM binding, and a live cell assay to demonstrate that the fusion proteins modulate transcriptional activation at a site that carries the target histone PTM. This pipeline will be useful for synthetic biologists who are interested in designing novel histone PTM binding actuators and probes. PMID- 29791134 TI - Identification of YTH Domain-Containing Proteins as the Readers for N1 Methyladenosine in RNA. AB - N1-methyladenosine (m1A) is an important post-transcriptional modification in RNA; however, the exact biological role of m1A remains to be determined. By employing a quantitative proteomics method, we identified multiple putative protein readers of m1A in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to m1A in RNA. We also found that Trp432 in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N6-methyladenosine (m6A), is required for its recognition of m1A. An analysis of previously published data revealed transcriptome-wide colocalization of YTH domain containing proteins and m1A sites in HeLa cells, suggesting that YTH domain containing proteins can bind to m1A in cells. Together, our results uncovered YTH domain-containing proteins as readers for m1A in RNA and provided new insight into the functions of m1A in RNA biology. PMID- 29791135 TI - Optically Active CdSe-Dot/CdS-Rod Nanocrystals with Induced Chirality and Circularly Polarized Luminescence. AB - Ligand-induced chirality in semiconductor nanocrystals (NCs) has attracted attention because of the tunable optical properties of the NCs. Induced circular dichroism (CD) has been observed in CdX (X = S, Se, Te) NCs and their hybrids, but circularly polarized luminescence (CPL) in these fluorescent nanomaterials has been seldom reported. Herein, we describe the successful preparation of l- and d-cysteine-capped CdSe-dot/CdS-rods (DRs) with tunable CD and CPL behaviors and a maximum anisotropic factor ( glum) of 4.66 * 10-4. The observed CD and CPL activities are sensitive to the relative absorption ratio of the CdS shell to the CdSe core, suggesting that the anisotropic g-factors in both CD and CPL increase to some extent for a smaller shell-to-core absorption ratio. In addition, the molar ratio of chiral cysteine to the DRs is investigated. Instead of enhancing the chiral interactions between the chiral molecules and DRs, an excess of cysteine molecules in aqueous solution inhibits both the CD and CPL activities. Such chiral and emissive NCs provide an ideal platform for the rational design of semiconductor nanomaterials with chiroptical properties. PMID- 29791136 TI - Precisely Striking Tumors without Adjacent Normal Tissue Damage via Mitochondria Templated Accumulation. AB - Ignored damage in adjacent normal tissue is fatal especially in some specific tumor therapy such as brain tumors, but it remains a great challenge to conquer due to random drug diffusion and tumor complexity. Herein, we show that hyperthermia in mitochondria, an interparticle plasmonic coupling effect activated nanoevent, selectively strikes tumor tissues without damaging adjacent normal tissues. Spherical gold nanoparticles with a mitochondria-targeting moiety, triphenyl phosphonium, preferentially accumulated inside tumor mitochondria and reached the threshold to activate interparticle plasmonic coupling effect among gold nanoparticles, realizing selective light-thermal conversion and mitochondrial dysfunction in tumor, whereas little hyperthermia and mitochondrial dysfunction were observed in adjacent normal tissues. In vivo study revealed that the temperature increment in tumor tissue with irradiation was nearly 4-fold that in adjacent normal tissue. This subcellular organelle templated accumulation strategy provides a therapeutic model for highly selective tumor therapy with negligible local side effects. PMID- 29791137 TI - The Chemistry of Lyophilized Blood Products. AB - With the development of new biologics and bioconjugates, storage and preservation have become more critical than ever before. Lyophilization is a method of cell and protein preservation by removing a solvent such as water from a substance followed by freezing. This technique has been used in the past and still holds promise for overcoming logistic challenges in safety net hospitals with limited blood banking resources, austere environments such as combat, and mass casualty situations where existing resources may be outstripped. This method allows for long-term storage and transport but requires the bioconjugation of preservatives to prevent cell destabilization. Trehalose is utilized as a bioconjugate in platelet and red blood cell preservation to maintain protein thermodynamics and stabilizing protein formulations in liquid and freeze-dried states. Biomimetic approaches have been explored as alternatives to cryo- and lyopreservation of blood components. Intravascular hemostats such as PLGA nanoparticles functionalized with PEG motifs, topical hemostats utilizing fibrinogen or chitosan, and liposomal encapsulated hemoglobin with surface modifications are effectively stored long-term through bioconjugation. In thinking about the best methods for storage and transport, we are focusing this topical review on blood products that have the longest track record of preservation and looking at how these methods can be applied to synthetic systems. PMID- 29791138 TI - Three-Dimensional Printed Poly(vinyl alcohol) Substrate with Controlled On-Demand Degradation for Transient Electronics. AB - Electronics that degrade after stable operation for a desired operating time, called transient electronics, are of great interest in many fields, including biomedical implants, secure memory devices, and environmental sensors. Thus, the development of transient materials is critical for the advancement of transient electronics and their applications. However, previous reports have mostly relied on achieving transience in aqueous solutions, where the transience time is largely predetermined based on the materials initially selected at the beginning of the fabrication. Therefore, accurate control of the transience time is difficult, thereby limiting their application. In this work, we demonstrate transient electronics based on a water-soluble poly(vinyl alcohol) (PVA) substrate on which carbon nanotube (CNT)-based field-effect transistors were fabricated. We regulated the structural parameters of the PVA substrate using a three-dimensional (3D) printer to accurately control and program the transience time of the PVA substrate in water. The 3D printing technology can produce complex objects directly, thus enabling the efficient fabrication of a transient substrate with a prescribed and controlled transience time. In addition, the 3D printer was used to develop a facile method for the selective and partial destruction of electronics. PMID- 29791139 TI - Dynamic Ligand Presentation in Biomaterials. AB - The native cell microenvironment is extraordinarily dynamic, with reciprocal regulation pathways between cells and the extracellular matrix guiding many physiological processes, such as cell migration, stem cell differentiation, and tissue formation. Providing the correct sequence of biochemical cues to cells, both in vivo and in vitro, is critical for triggering specific biological outcomes. There has been a diversity of methods developed for exposing cells in culture to spatiotemporally varying cues, many of which have centered on dynamic control over cell-material interactions in an attempt to recapitulate the role of the extracellular matrix in cell signaling. This review highlights several mechanisms that have been employed to control bioactive ligand presentation in biomaterials, and looks ahead toward the potential for genetically encoded approaches to dynamically regulate material bioactivity using light. PMID- 29791140 TI - Correlative Stimulated Emission Depletion and Scanning Ion Conductance Microscopy. AB - Correlation microscopy combining fluorescence and scanning probe or electron microscopy is limited to fixed samples due to the sample preparation and nonphysiological imaging conditions required by most probe or electron microscopy techniques. Among the few scanning probe techniques that allow imaging of living cells under physiological conditions, scanning ion conductance microscopy (SICM) has been shown to be the technique that minimizes the impact on the investigated sample. However, combinations of SICM and fluorescence microscopy suffered from the mismatch in resolution due to the limited resolution of conventional light microscopy. In the last years, the diffraction limit of light microscopy has been circumvented by various techniques, one of which is stimulated emission depletion (STED) microscopy. Here, we aimed at demonstrating the combination of STED and SICM. We show that both methods allow recording a living cellular specimen and provide a SICM and STED image of the same sample, which allowed us to correlate the membrane surface topography and the distribution of the cytoskeletal protein actin. Our proof-of-concept study exemplifies the benefit of correlating SICM with a subdiffraction fluorescence method and might form the basis for the development of a combined instrument that would allow the simultaneous recording of subdiffraction fluorescence and topography information. PMID- 29791141 TI - Fluorogenic Probing of Membrane Protein Trafficking. AB - Methods to differentially label cell-surface and intracellular membrane proteins are indispensable for understanding their function and the regulation of their trafficking. We present an efficient strategy for the rapid and selective fluorescent labeling of membrane proteins based on the chemical-genetic fluorescent marker FAST (fluorescence-activating and absorption-shifting tag). Cell-surface FAST-tagged proteins could be selectively and rapidly labeled using fluorogenic membrane-impermeant 4-hydroxybenzylidene rhodanine (HBR) analogs. This approach allows the study of protein trafficking at the plasma membrane with various fluorometric techniques, and opens exciting prospects for the high throughput screening of small molecules able to restore disease-related trafficking defects. PMID- 29791142 TI - Reassessment of the Transport Mechanism of the Human Zinc Transporter SLC39A2. AB - The human zinc transporter SLC39A2, also known as ZIP2, was shown to mediate zinc transport that could be inhibited at pH <7.0 and stimulated by HCO3-, suggesting a Zn2+/HCO3- cotransport mechanism [Gaither, L. A., and Eide, D. J. (2000) J. Biol. Chem. 275, 5560-5564]. In contrast, recent experiments in our laboratory indicated that the functional activity of ZIP2 increases at acidic pH [Franz, M. C., et al. (2014) J. Biomol. Screening 19, 909-916]. The study presented here was therefore designed to reexamine the findings about the pH dependence and to extend the functional characterization of ZIP2. Our current results show that ZIP2-mediated transport is modulated by extracellular pH but independent of the H+ driving force. Also, in our experiments, ZIP2-mediated transport is not modulated by extracellular HCO3-. Moreover, a high extracellular [K+], which induces depolarization, inhibited ZIP2-mediated transport, indicating that the transport mechanism is voltage-dependent. We also show that ZIP2 mediates the uptake of Cd2+ ( Km ~ 1.57 MUM) in a pH-dependent manner ( KH+ ~ 66 nM). Cd2+ transport is inhibited by extracellular [Zn2+] (IC50 ~ 0.32 MUM), [Cu2+] (IC50 ~ 1.81 MUM), and to a lesser extent [Co2+], but not by [Mn2+] or [Ba2+]. Fe2+ is not transported by ZIP2. Accordingly, the substrate selectivity of ZIP2 decreases in the following order: Zn2+ > Cd2+ >= Cu2+ > Co2+. Altogether, we propose that ZIP2 is a facilitated divalent metal ion transporter that can be modulated by extracellular pH and membrane potential. Given that ZIP2 expression has been reported in acidic environments [Desouki, M. M., et al. (2007) Mol. Cancer 6, 37; Inoue, Y., et al. (2014) J. Biol. Chem. 289, 21451-21462; Tao, Y. T., et al. (2013) Mol. Biol. Rep. 40, 4979-4984], we suggest that the herein described H+ mediated regulatory mechanism might be important for determining the velocity and direction of the transport process. PMID- 29791144 TI - Environmental Risks of Medium-Chain Chlorinated Paraffins (MCCPs): A Review. AB - Chlorinated paraffins are industrial chemicals that can be subdivided into short chain (SCCP), medium-chain (MCCP), and long-chain (LCCP) chlorinated paraffins. The global production volumes of MCCPs are nowadays suspected to be much higher than those of S- and LCCPs, and the few available studies on the environmental occurrence of chlorinated paraffins report often higher MCCP concentrations than S- or LCCP concentrations in the environment. The present review focuses, therefore, on MCCPs specifically and provides a literature overview and a data analysis of the production volumes, PBT properties (persistence, bioaccumulation potential, and toxicity), and the worldwide measured concentrations of MCCP in environmental samples, biota, and humans. Furthermore, we include our own measurements of technical CP formulations from China, the major global producing country, to estimate the global production amounts of MCCPs. The key findings from this review are that (1) MCCPs are toxic to the aquatic environment, and the available data suggest that they are also persistent; (2) available time trends for MCCPs in soil, biota, and most of the sediment cores show increasing time trends over the last years to decades; and (3) MCCP concentrations in sediment close to local sources exceed toxicity thresholds (i.e., the PNEC). Our study shows that overall, MCCPs are of growing concern, and regulatory actions should be considered seriously. PMID- 29791143 TI - Water-Soluble Silver(I) Complexes Featuring the Hemilabile 3,7-Dimethyl-1,3,5 triaza-7-phosphabicyclo[3.3.1]nonane Ligand: Synthesis, Characterization, and Antimicrobial Activity. AB - This paper describes the preparation and comprehensive characterization of a series of water-soluble cationic silver(I)-centered complexes featuring the hemilabile P, N-ligand known as 3,7-dimethyl-1,3,5-triaza-7 phosphabicyclo[3.3.1]nonane (herein abbreviated as PTN(Me)) and differing types of monoanionic counterions including known biologically active sulfadiazine and triclosan. The complexes primarily differed though the number of coordinating PTN(Me) ligands. The bis-substituted Ag(I) complexes revealed P, N bidentate coordination, while the only P-monocoordination of the metal center was observed for the tris-substituted systems. The bis-ligated silver compounds were observed to quickly degrade upon photoexposure or in contact with air. In contrast, the tris-ligated complexes demonstrated greater stability, in particular, a high resistance to photo-decomposition. Calculated geometry optimized models using the density functional theory method (BP86) revealed for the bis-substituted PTN(Me) Ag(I) species that the total enthalpy of the tetrahedral C2-symmetric structure is marginally lower by -0.6 kcal mol-1 compared to the planar C2 h structure, which is analogous for the corresponding [Au(PTN(Me))2]+ complex with Delta H = 0.5 kcal mol-1. Hence both types of complexes feature free rotation of the PTN ligand about the M-P bond axis. This series of Ag(I) and bis-PTN(Me) Au(I) complexes were evaluated using the agar well diffusion test for potential antimicrobial and antifungal activity. The nature of the counterion was found to have a strong correlation with the area of microbiological growth inhibition. Silver(I) complexes bearing the deprotonated triclosan as the counterion demonstrated the greatest activity, with large zones of growth inhibition, with the tris-ligated triclosan complex obtaining of a high clearance of 42 mm against the Gram-negative Escherichia coli. In contrast, the previously reported [Au(PTN(Me))2]Cl complex demonstrated activity only against E. coli, which is lower than that observed for the silver(I) PTN(Me) species. PMID- 29791145 TI - Slow-Starter Enzymes: Role of Active-Site Architecture in the Catalytic Control of the Biosynthesis of Taxadiene by Taxadiene Synthase. AB - Taxadiene synthase (TXS) catalyzes the formation of natural product taxa 4(5),11(12)-diene (henceforth taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anticancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of taxadiene by TXS using a hybrid quantum mechanics-molecular mechanics potential in conjunction with free energy simulation methods. The obtained free-energy landscape displays initial endergonic steps followed by a stepwise downhill profile, which is an emerging free-energy fingerprint for type I terpene synthases. We identify an active-site Trp residue (W753) as a key feature of the TXS active-site architecture and propose that this residue stabilized intermediate cations via pi-cation interactions. To validate our proposed active TXS model, we examine a previously reported W753H mutation, which leads to the exclusive formation of side product cembrene A. The simulations of the W753H mutant show that, in the mutant structure, the His side chain is in the perfect position to deprotonate the cembrenyl cation en route to cembrene formation and that this abortive deprotonation is an energetically facile process. On the basis of the current model, we propose that an analogous mutation of Y841 to His could possibly lead to verticillane. The current simulations stress the importance of the precise positioning of key active-site residues in stabilizing intermediate carbocations. In view of the great pharmaceutical importance of taxadiene, a detailed understanding of the TXS mechanism can provide important clues toward a synthetic strategy for Taxol manufacturing. PMID- 29791146 TI - Effect of Cholesterol on Membrane Dipole Potential: Atomistic and Coarse-Grained Molecular Dynamics Simulations. AB - The effect of cholesterol on membrane dipole potential has been the subject of a great number of experimental and theoretical investigations, but these studies have yielded different findings and interpretations at high cholesterol concentrations. This suggests that the underlying mechanism of the cholesterol effect is not well addressed. Moreover, as far as we know, none of the previously proposed coarse-grained (CG) models (including MARTINI and its improved versions) have been successfully used to probe the effect of cholesterol on membrane dipole potential, owing to either an inaccurate description of water-cholesterol electrostatics or the neglect of the contribution of cholesterol to membrane dipole potential. In our previous works, we proposed a CG model CAVS (charge attached to virtual site) for lipid and water, showing the advantage of the CAVS model in the calculations of membrane dipole potential as compared to the MARTINI model. In this work, we present the CAVS model for cholesterol in order to enable us to investigate the effect of cholesterol on membrane dipole potential at large spatial scale. Our works showed that the CAVS and CHARMM models produced similar results in the study of the effects of cholesterol on lipid bilayer structures and membrane dipole potential. In particular, by combining the CHARMM and CAVS simulations, we explicitly calculated the individual contributions of membrane components (cholesterol, water, and lipid) to membrane dipole potential at different cholesterol concentrations, and we discovered that an increase in cholesterol content would result in a nonlinear variation of the individual contributions of water and lipid with cholesterol concentration. On the other side, we observed that the individual contribution of cholesterol to membrane dipole potential would nonlinearly increase with increasing cholesterol concentration. Thus, the effect of cholesterol on membrane dipole potential is complicated owing to the different variation of individual contributions of membrane components (water, lipid, and cholesterol) with cholesterol concentration. PMID- 29791147 TI - Investigations of the Magnetic and Spectroscopic Properties of V(III) and V(IV) Complexes. AB - Herein, we utilize a variety of physical methods including magnetometry (SQUID), electron paramagnetic resonance (EPR), and magnetic circular dichroism (MCD), in conjunction with high-level ab initio theory to probe both the ground and ligand field excited electronic states of a series of V(IV) ( S = 1/2) and V(III) ( S = 1) molecular complexes. The ligand fields of the central metal ions are analyzed with the aid of ab initio ligand-field theory (AILFT), which allows for a chemically meaningful interpretation of multireference electronic structure calculations at the level of the complete-active-space self-consistent field with second-order N-electron valence perturbation theory. Our calculations are in good agreement with all experimentally investigated observables (magnetic properties, EPR, and MCD), making our extracted ligand-field theory parameters realistic. The ligand fields predicted by AILFT are further analyzed with conventional angular overlap parametrization, allowing the ligand field to be decomposed into individual sigma- and pi-donor contributions from individual ligands. The results demonstrate in VO2+ complexes that while the axial vanadium-oxo interaction dominates both the ground- and excited-state properties of vanadyl complexes, proximal coordination can significantly modulate the vanadyl bond covalency. Similarly, the electronic properties of V(III) complexes are particularly sensitive to the available sigma and pi interactions with the surrounding ligands. The results of this study demonstrate the power of AILFT-based analysis and provide the groundwork for the future analysis of vanadium centers in homogeneous and heterogeneous catalysts. PMID- 29791148 TI - Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate. AB - Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for simple diffusion. The free energy profile allowed us to obtain a direct rigorous estimate of the pre-exponential factor for the folding dynamics. PMID- 29791149 TI - A Tricopper(I) Complex Competent for O Atom Transfer, C-H Bond Activation, and Multiple O2 Activation Steps. AB - Oxygenation of a tricopper(I) cyclophanate (1) affords reactive transients competent for C-H bond activation and O atom transfer to various substrates (including toluene, dihydroanthracene, and ethylmethylsulfide) based on 1H NMR, gas chromatography/mass spectrometry (MS), and electrospray ionization (ESI)/MS data. Low product yields (<1%) are determined for C-H activation substrates (e.g, toluene, ethylbenzene), which we attribute to competitive ligand oxidation. The combined stopped-flow UV/visible, electron paramagnetic resonance, ESI/MS, 1H NMR, and density functional theory (DFT) results for reaction of 1 with O2 are consistent with transient peroxo- and di(oxo)-bridged intermediates. DFT calculations elucidate a concerted proton-coupled electron transfer from toluene to the di(MU-oxo) intermediate and subsequent radical rebound as the C-H activation mechanism. Our results support a multicopper oxidase-like mechanism for O2 activation by 1, traversing species similar to the coplanar Cu3O2 unit in the peroxy and native intermediates. PMID- 29791150 TI - Elastin-like Polypeptide (ELP) Charge Influences Self-Assembly of ELP-mCherry Fusion Proteins. AB - Self-assembly of protein-polymer bioconjugates presents an elegant strategy for controlling nanostructure and orientation of globular proteins in functional materials. Recent work has shown that genetic fusion of globular protein mCherry to an elastin-like polypeptide (ELP) yields similar self-assembly behavior to these protein-polymer bioconjugates. In the context of studying protein-polymer bioconjugate self-assembly, the mutability of the ELP sequence allows several different properties of the ELP block to be tuned orthogonally while maintaining consistent polypeptide backbone chemistry. This work uses this ELP sequence tunability in combination with the precise control offered by genetic engineering of an amino acid sequence to generate a library of four novel ELP sequences that are used to study the combined effect of charge and hydrophobicity on ELP-mCherry fusion protein self-assembly. Concentrated solution self-assembly is studied by small-angle X-ray scattering (SAXS) and depolarized light scattering (DPLS). These experiments show that fusions containing a negatively charged ELP block do not assemble at all, and fusions with a charge balanced ELP block exhibit a weak propensity for assembly. By comparison, the fusion containing an uncharged ELP block starts to order at 40 wt % in solution and at all concentrations measured has sharper, more intense SAXS peaks than other fusion proteins. These experiments show that charge character of the ELP block is a stronger predictor of self-assembly behavior than the hydrophobicity of the ELP block. Dilute solution small-angle neutron scattering (SANS) on the ELPs alone suggests that all ELPs used in this study (including the uncharged ELP) adopt dilute solution conformations similar to those of traditional polymers, including polyampholytes and polyelectrolytes. Finally, dynamic light scattering studies on ELP-mCherry blends shows that there is no significant complexation between the charged ELPs and mCherry. Therefore, it is proposed that the superior self-assembly of fusion proteins containing uncharged ELP block is due to effective repulsions between charged and uncharged blocks due to local charge correlation effects and, in the case of anionic ELPs, repulsion between like charges within the ELP block. PMID- 29791151 TI - Recent Advances and Progress on Melanin-like Materials and Their Biomedical Applications. AB - Melanins are well-known biopolymers that are ubiquitous in nature, distributed widely in microorganisms, plants, and animals, and play significant physiological roles. They are mostly biopolymers formed from phenolic compounds by polymerization via quinones. Poly(dopamine) (PDA), a melanin-like material, is similar in structure and properties to eumelanin and has attracted considerable interest for various types of biological applications. This review outlines the recent advances in the structure and synthesis of PDA and discusses applications of PDA in many biological fields, such as biological imaging, photothermal therapy, and drug delivery systems. The purpose of this review is to give a brief overview of the synthesized procedures, structure, biomedical applications, and prospects of melanin-like materials. PMID- 29791152 TI - Improved Force Fields for Peptide Nucleic Acids with Optimized Backbone Torsion Parameters. AB - Peptide nucleic acids are promising nucleic acid analogs for antisense therapies as they can form stable duplex and triplex structures with DNA and RNA. Computational studies of PNA-containing duplexes and triplexes are an important component for guiding their design, yet existing force fields have not been well validated and parametrized with modern computational capabilities. We present updated CHARMM and Amber force fields for PNA that greatly improve the stability of simulated PNA-containing duplexes and triplexes in comparison with experimental structures and allow such systems to be studied on microsecond time scales. The force field modifications focus on reparametrized PNA backbone torsion angles to match high-level quantum mechanics reference energies for a model compound. The microsecond simulations of PNA-PNA, PNA-DNA, PNA-RNA, and PNA DNA-PNA complexes also allowed a comprehensive analysis of hydration and ion interactions with such systems. PMID- 29791153 TI - A Probabilistic Framework for Constructing Temporal Relations in Replica Exchange Molecular Trajectories. AB - Knowledge of the structure and dynamics of biomolecules is essential for elucidating the underlying mechanisms of biological processes. Given the stochastic nature of many biological processes, like protein unfolding, it is almost impossible that two independent simulations will generate the exact same sequence of events, which makes direct analysis of simulations difficult. Statistical models like Markov chains, transition networks, etc. help in shedding some light on the mechanistic nature of such processes by predicting long-time dynamics of these systems from short simulations. However, such methods fall short in analyzing trajectories with partial or no temporal information, for example, replica exchange molecular dynamics or Monte Carlo simulations. In this work, we propose a probabilistic algorithm, borrowing concepts from graph theory and machine learning, to extract reactive pathways from molecular trajectories in the absence of temporal data. A suitable vector representation was chosen to represent each frame in the macromolecular trajectory (as a series of interaction and conformational energies), and dimensionality reduction was performed using principal component analysis (PCA). The trajectory was then clustered using a density-based clustering algorithm, where each cluster represents a metastable state on the potential energy surface (PES) of the biomolecule under study. A graph was created with these clusters as nodes with the edges learned using an iterative expectation maximization algorithm. The most reactive path is conceived as the widest path along this graph. We have tested our method on RNA hairpin unfolding trajectory in aqueous urea solution. Our method makes the understanding of the mechanism of unfolding in the RNA hairpin molecule more tractable. As this method does not rely on temporal data, it can be used to analyze trajectories from Monte Carlo sampling techniques and replica exchange molecular dynamics (REMD). PMID- 29791154 TI - High-Precision Megahertz-to-Terahertz Dielectric Spectroscopy of Protein Collective Motions and Hydration Dynamics. AB - The low-frequency collective vibrational modes in proteins as well as the protein water interface have been suggested as dominant factors controlling the efficiency of biochemical reactions and biological energy transport. It is thus crucial to uncover the mystery of the hydration structure and dynamics as well as their coupling to collective motions of proteins in aqueous solutions. Here, we report dielectric properties of aqueous bovine serum albumin protein solutions as a model system using an extremely sensitive dielectric spectrometer with frequencies spanning from megahertz to terahertz. The dielectric relaxation spectra reveal several polarization mechanisms at the molecular level with different time constants and dielectric strengths, reflecting the complexity of protein-water interactions. Combining the effective-medium approximation and molecular dynamics simulations, we have determined collective vibrational modes at terahertz frequencies and the number of water molecules in the tightly bound and loosely bound hydration layers. High-precision measurements of the number of hydration water molecules indicate that the dynamical influence of proteins extends beyond the first solvation layer, to around 7 A distance from the protein surface, with the largest slowdown arising from water molecules directly hydrogen bonded to the protein. Our results reveal critical information of protein dynamics and protein-water interfaces, which determine biochemical functions and reactivity of proteins. PMID- 29791155 TI - Deciphering Stability of Five-Membered Heterocyclic Radicals: Balancing Act Between Delocalization and Ring Strain. AB - Computational studies on five-membered heterocycles with single heteroatom and their isomeric dehydro-borole 1a-1c, cyclopentadiene 2a-2c, pyrrole 3a-3c, furan 4b-4c, phosphole 5a-5c, and thiophene 6b-6c radicals have been carried out. Geometrical aspects through ground state electronic structures and stability aspects using bond dissociation energies (BDE) and radical stabilization energies (RSE) have been envisaged in this regard. Spin densities, electrostatic potentials (ESP), and natural bond orbital (NBO) analysis unveiled the extent of spin delocalization. The estimated nucleus-independent chemical shifts (NICS) values revealed the difference in aromaticity characteristics of radicals. Particularly the heteroatom centered radicals exhibit odd electron pi-delocalized systems with a quasi-antiaromatic character. Various factors such as, the relative position of the radical center with respect to heteroatoms, resonance, ring strain and orbital interactions influence the stability that follows the order: heteroatom centered > beta-centered > alpha-centered radicals. Among the influences of various factors, we confirmed the existence of a competition between delocalization and the ring strain, and the interplay of both decides the overall stability order. PMID- 29791156 TI - Ab Initio Potential Energy Surfaces of C3 Collision with Proton and Quantum Dynamics of Rotational Transition. AB - New ab initio potential energy surfaces have been generated for the ground state and low-lying excited states of the H+ + C3 system using the multireference configuration interaction (MRCI) method with Dunning's augmented correlation consistent polarized valence quadruple-zeta (aug-cc-pVQZ) basis sets. The ground state and low-lying excited states show avoided crossing, indicating nonadiabatic coupling. The anisotropy of the ground-state surface has been analyzed by computing the multipolar expansion coefficients with the frozen C-C equilibrium bond length. The asymptotic potential has been merged with the interaction potential by spline fit. This potential is then used in the full close coupling calculations of rotational excitation in C3 collision with the proton for rotational levels j = 0, 2, 4, 6, 8 at very low collision energy. By averaging the cross sections over a Boltzmann distribution of velocities of the incoming atom, we obtain and discuss corresponding rate coefficients of C3 collision with the proton in the interstellar medium. PMID- 29791157 TI - Hybrid Correlation Energy (HyCE): An Approach Based on Separate Evaluations of Internal and External Components. AB - A novel hybrid correlation energy (HyCE) approach is proposed that determines the total correlation energy via distinct computation of its internal and external components. This approach evolved from two related studies. First, rigorous assessment of the accuracies and size extensivities of a number of electron correlation methods, that include perturbation theory (PT2), coupled-cluster (CC), configuration interaction (CI), and coupled electron pair approximation (CEPA), shows that the CEPA(0) variant of the latter and triples-corrected CC methods consistently perform very similarly. These findings were obtained by comparison to near full CI results for four small molecules and by charting recovered correlation energies for six steadily growing chain systems. Second, by generating valence virtual orbitals (VVOs) and utilizing the CEPA(0) method, we were able to partition total correlation energies into internal (or nondynamic) and external (or dynamic) parts for the aforementioned six chain systems and a benchmark test bed of 36 molecules. When using triple-zeta basis sets it was found that per orbital internal correlation energies were appreciably larger than per orbital external energies and that the former showed far more chemical variation than the latter. Additionally, accumulations of external correlation energies were seen to proceed smoothly, and somewhat linearly, as the virtual space is gradually increased. Combination of these two studies led to development of the HyCE approach, whereby the internal and external correlation energies are determined separately by CEPA(0)/VVO and PT2/external calculations, respectively. When applied to the six chain systems and the 36-molecule benchmark test set it was found that HyCE energies followed closely those of triples-corrected CC and CEPA(0) while easily outperforming MP2 and CCSD. The success of the HyCE approach is more notable when considering that its cost is only slightly more than MP2 and significantly cheaper than the CC approaches. PMID- 29791158 TI - Electronic Structure of OsSi Calculated by MS-NEVPT2 with Inclusion of the Relativistic Effects. AB - The electronic states of OsSi are calculated by multi-state N-electron valence state second order perturbation theory (MS-NEVPT2) with all-electron basis sets. The relativistic effects are considered comprehensively that allows us to identify the X3Sigma0+- ground state. The theoretical equilibrium bond length 2.103 A is close to the experimental measurement of 2.1207 A while the vibrational frequency 466 cm-1 is smaller than the experimental value of 516 cm 1. Two excited states, namely 3Pi1(I) and 3Pi1(II), are located at 15568 and 18316 cm-1 above the ground state, respectively. The 3Pi1(I) <- X3Sigma0+- transition has been assigned to the experimental spectra at 15729 cm-1 and 3Pi1(II) <- X3Sigma0+- may produce the bands near 18469 cm-1. Although the latter transition energy is in accord with the experimental spectra, theoretical calculations give too small oscillator strength. Moreover, plenty of excited states with considerable oscillator strengths are located that could serve as reference data in future experiments. The four low-lying states of OsC are also calculated for comparison. PMID- 29791159 TI - Reaction Kinetics of Hydrogen Atom Abstraction from C4-C6 Alkenes by the Hydrogen Atom and Methyl Radical. AB - Alkenes are important ingredients of realistic fuels and are also critical intermediates during the combustion of a series of other fuels including alkanes, cycloalkanes, and biofuels. To provide insights into the combustion behavior of alkenes, detailed quantum chemical studies for crucial reactions are desired. Hydrogen abstractions of alkenes play a very important role in determining the reactivity of fuel molecules. This work is motivated by previous experimental and modeling evidence that current literature rate coefficients for the abstraction reactions of alkenes are still in need of refinement and/or redetermination. In light of this, this work reports a theoretical and kinetic study of hydrogen atom abstraction reactions from C4-C6 alkenes by the hydrogen (H) atom and methyl (CH3) radical. A series of C4-C6 alkene molecules with enough structural diversity are taken into consideration. Geometry and vibrational properties are determined at the B3LYP/6-31G(2df,p) level implemented in the Gaussian-4 (G4) composite method. The G4 level of theory is used to calculate the electronic single point energies for all species to determine the energy barriers. Conventional transition state theory with Eckart tunneling corrections is used to determine the high-pressure-limit rate constants for 47 elementary reaction rate coefficients. To faciliate their applications in kinetic modeling, the obtained rate constants are given in the Arrhenius expression and rate coefficients for typical reaction classes are recommended. The overall rate coefficients for the reaction of H atom and CH3 radical with all the studied alkenes are also compared. Branching ratios of these reaction channels for certain alkenes have also been analyzed. PMID- 29791160 TI - Interaction of Zwitterionic and Ionic Monomers with Graphene Surfaces. AB - Measurement of the interaction force between two materials provides important information on various properties, such as adsorption, binding, or compatibility for coatings, adhesion, and composites. The interaction forces of zwitterionic and ionic monomers with graphite platelets (G) and reduced graphene oxide (rGO) surfaces were systematically investigated by atomic force microscopy (AFM) in air and water. The monomers examined were 2-(methacryloyloxy)ethyl 2 (trimethylammonio)ethyl phosphate (MPC), [2-(methacryloyloxy)ethyl]dimethyl-(3 sulfopropyl)ammonium hydroxide (SBE), [2-(acryloyloxy)ethyl]trimethylammonium chloride (ATC), and 2-methyl-2-propene-1-sulfonic acid sodium (MSS). The AFM studies revealed that MSS and SBE monomers with sulfonate units have stronger interaction forces with G surface in air and that MPC and ATC monomers with quaternary ammonium units have higher interaction forces in water. In the case of rGO surface, the monomers with quaternary ammonium units showed stronger interactions regardless of the medium. These interactions could be rationalized by the interaction mechanism between the monomers with graphene surfaces, such as cation-pi for MPC and ATC and anion-pi for MSS and SBE. Overall, cation-pi interactions were effective in water, whereas anion-pi interactions are effective in air with G surface. The adhesion values of MPC, SBE, ATC, and MSS on rGO were lower than the values measured on G surface. Among the monomers, MPC showed the highest dispersibility for aqueous graphene dispersions. Further, the adsorption of MPC on G and rGO surfaces was verified by high-resolution transmission electron microscopy and X-ray diffraction patterns. PMID- 29791161 TI - A Tetrazine-Labile Vinyl Ether Benzyloxycarbonyl Protecting Group (VeZ): An Orthogonal Tool for Solid-Phase Peptide Chemistry. AB - The vinyl ether benzyloxycarbonyl (VeZ) protecting group is selectively cleaved by treatment with tetrazines via an inverse electron-demand Diels-Alder reaction. This represents a new orthogonal protecting group for solid-phase peptide synthesis, with Fmoc-Lys(VeZ)-OH as a versatile alternative to Fmoc-Lys(Alloc)-OH and Fmoc-Lys(Dde)-OH, as demonstrated by the synthesis of two biologically relevant cyclic peptides. PMID- 29791163 TI - Relationship between Excited State Lifetime and Isomerization Quantum Yield in Animal Rhodopsins: Beyond the One-Dimensional Landau-Zener Model. AB - We show that the speed of the chromophore photoisomerization of animal rhodopsins is not a relevant control knob for their light sensitivity. This result is at odds with the momentum-driven tunnelling rationale (i.e., assuming a one dimensional Landau-Zener model for the decay: Zener, C. Non-Adiabatic Crossing of Energy Levels. Proc. R. Soc. London, Ser. A 1932, 137 (833), 696-702) holding that a faster nuclear motion through the conical intersection translates into a higher quantum yield and, thus, light sensitivity. Instead, a model based on the phase-matching of specific excited state vibrational modes should be considered. Using extensive semiclassical hybrid quantum mechanics/molecular mechanics trajectory computations to simulate the photoisomerization of three animal rhodopsin models (visual rhodopsin, squid rhodopsin and human melanopsin), we also demonstrate that phase-matching between three different modes (the reactive carbon and hydrogen twisting coordinates and the bond length alternation mode) is required to achieve high quantum yields. In fact, such "phase-matching" mechanism explains the computational results and provides a tool for the prediction of the photoisomerization outcome in retinal proteins. PMID- 29791162 TI - Manganese-Catalyzed Direct Conversion of Ester to Amide with Liberation of H2. AB - A simple and efficient Mn-catalyzed acylation of amines is achieved using both acyl and alkoxy functions of unactivated esters with the liberation of molecular hydrogen as a sole byproduct. The present protocol provides an atom-economical and sustainable route for the synthesis of amides from esters by employing an earth-abundant manganese salt and inexpensive phosphine-free tridentate ligand. PMID- 29791164 TI - Preparation of Thioanisole Biscarbanion and C-H Lithiation/Annulation Reactions for the Access of Five-Membered Heterocycles. AB - The synthesis, isolation, and X-ray structure of a thioanisole-based trilithium complex are reported. On the basis of the double-lithiation strategy, two novel synthetic methodologies have been developed under mild reaction conditions (room temperature): (1) reactions of lithiated thioanisoles with nitriles give benzoisothiazoles via a [3 + 2]-type of approach with two new bond formations and (2) formation of benzothiophenes from thioanisoles and amides through a [4 + 1] pattern forming 4 new chemical bonds. PMID- 29791165 TI - Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug Polymer Blends at Ambient Pressure. AB - Rational selection of polymers for amorphous drug stabilization is necessary for further successful development of solid dispersion technology. In this paper, we investigate the effect of polymer chain length on the inhibition of amorphous drug recrystallization. To consider this problem, we prepared a drug-polymer blend (in 10:1 drug to polymer ratio) containing bicalutamide (BIC) and polyvinylpyrrolidone (PVP) with different chain lengths K10, K30, and K90. We applied broadband dielectric spectroscopy to compare the molecular dynamics of investigated samples and thoroughly recognize their crystallization tendencies from supercooled liquid state. Despite the lack of differences in molecular dynamics, we noticed significant changes in their crystallization rates. To rationalize such behavior, we performed positron annihilation lifetime spectroscopy measurements. The results showed that the value of free volume was the highest for blend with PVP K90, which at the same time was characterized by the greatest tendency to crystallize. We postulate that the polymer chain, depending on its length, can have different configurations in the space, leading to better or worse sample stabilization. Our results highlight how important is detailed understanding of physical properties of polymers for judicious selection of the best stabilization approach. PMID- 29791167 TI - Vibration-Assisted and Vibration-Hampered Excitonic Quantum Transport. AB - The interplay between excitons and vibrations is considered to be a key factor in determining the exciton-transfer properties in light-harvesting complexes. Here we study this interplay theoretically in a model for exciton transport, composed of two chromophores coupled to an exciton source and sink in the presence of vibrations. We consider two cases that show qualitatively distinct transport features. In the first, the vibrations are global and affect the two chromophores simultaneously. In the second case, the vibrations are localized on each chromophore. For global vibrations, the current exhibits antiresonances as a function of the chromophore energy difference, which are due to exciton-polaron interference. For local vibrations, on the contrary, the currents show tunneling resonances at multiples of the vibration energy. Counterintuitively, both effects increase with increasing temperature. Our results demonstrate that an environment can either assist or hamper exciton transport and is in accord with the current understanding of energy transfer in natural exciton-transfer complexes. PMID- 29791166 TI - Intervalley Scattering of Interlayer Excitons in a MoS2/MoSe2/MoS2 Heterostructure in High Magnetic Field. AB - Degenerate extrema in the energy dispersion of charge carriers in solids, also referred to as valleys, can be regarded as a binary quantum degree of freedom, which can potentially be used to implement valleytronic concepts in van der Waals heterostructures based on transition metal dichalcogenides. Using magneto photoluminescence spectroscopy, we achieve a deeper insight into the valley polarization and depolarization mechanisms of interlayer excitons formed across a MoS2/MoSe2/MoS2 heterostructure. We account for the nontrivial behavior of the valley polarization as a function of the magnetic field by considering the interplay between exchange interaction and phonon-mediated intervalley scattering in a system consisting of Zeeman-split energy levels. Our results represent a crucial step toward the understanding of the properties of interlayer excitons with strong implications for the implementation of atomically thin valleytronic devices. PMID- 29791168 TI - Impact of surgery on quality of life in Crohn's disease patients: final results of Czech cohort. AB - INTRODUCTION: Crohns disease (CD) belongs to chronic diseases that highly affect the patient's quality of life (QoL). The effect of the disease and impairment of QoL in CD patients is already known. The aim was to assess how surgical treatment influences the patients QoL and determine factors that can affect postoperative QoL. METHODS AND PATIENTS: We compared the QoL before and after surgery in patients who had undergone a bowel resection at our department due to CD between 2010-2016. The patients filled in a standardized QLQ-CR29 questionnaire to assess QoL in the preoperative period and the postoperative period after a 2-month interval. The control groups were CD patients who had not undergone surgical treatment (bowel resection) and a healthy cohort. In the QoL evaluation, 132 patients with CD who had undergone surgery (bowel resection), 83 patients with CD without an operation and 104 healthy subjects were enrolled. RESULTS: 104 of the operated patients experienced a postoperative improvement of the overall QoL (78.8 %), 2 patients did not register any changes in QoL (1.5 %) and 26 patients (19.7 %) experienced a worsening of their postoperative QoL. The results were statistically significant (p < 0.001). CONCLUSION: We detected a significant improvement of the overall QoL after surgical resection in CD patients (measured 2 months after surgery). Gender was identified as the only statistically relevant factor with influence on postoperative QoL.Key words: bowel resection - Crohn's disease - Czech cohort - inflammatory bowel disease - quality of life - surgical treatment. PMID- 29791169 TI - [Epicardial fat and osteoprotegerin - does a mutual relation exist? Pilot study]. AB - INTRODUCTION: Epicardial fat (EPI) plays important role in development of metabolic and cardiovascular diseases. According to population studies EPI represents independent risk factor of cardiovascular diseases (CVD) and also for neoplasms. Osteoprotegerin (OPG) is a glycoprotein which have role in regulation of immune and cardiovascular systems. High serum levels of OPG are connected with high cardiovascular risk. The aim of our study was to evaluate possible correlation between EPI and OPG level in asymptomatic relatives of patients with CVD. MATERIAL AND METHODS: 53 asymptomatic relatives (37 male) (median age 53 years) of patients with CVD (ischemic heart disease, cerebrovascular disease) were included. Physical examination and biochemistry analysis were performed. GE Vivid 7 (GE Medical) was used for echocardiography. EPI was measured according to guidelines using parasternal long axis in diastole as a space in front of right ventricle. RESULTS: EPI was present in 46 subjects (86.8 %) with mean value of 2.91 mm. In 10 subjects was the amount of EPI > 5 mm. Spearmann correlation analysis found statistically significant correlation between EPI and OPG (r = 0.271; p = 0.05) and age (r = 0.500; p < 0.0001). We have not found correlation between EPI, glycaemia and level of insulin, glycated Hb, total, LDL, HDL cholesterol and triglycerides. CONCLUSION: We have found positive correlation between EPI and OPG. More studies are needed to confirm applicability of this correlation in risk stratification.Key words: cardiovascular risk - epicardial fat - osteoprotegerin. PMID- 29791170 TI - Effectiveness and safety of lixisenatide for treatment of diabetes in the real world: data from the Monitoring Registry in a Real-Life Cohort in the Czech and Slovak Republic. AB - INTRODUCTION: GLP1 receptor agonist lixisenatide has demonstrated its efficacy in numerous clinical trials, nevertheless its real-life effectiveness data is limited. AIM: To describe effectiveness and safety of lixisenatide in routine clinical practice in the Czech Republic and the Slovak Republic, as recorded by the Registry-Based Observational Study. METHODS: Multinational, multicenter, observational, non-interventional, 6-month prospective product registry of patients with type 2 diabetes mellitus aged > 18 years who were initiating therapy with lixisenatide. Patients were enrolled into this registry, provided written informed consent, between 1 May 2013 and 31 December 2015. Evaluations were performed at baseline and after 3 and 6 months of lixisenatide treatment. The primary objective of the study was the absolute change in glycated hemoglobin (HbA1c) from baseline to month 6 after lixisenatide initiation. The study was approved by responsible ethics committees and performed in accordance with the Helsinki Declaration. Informed consent was obtained from all patients before enrolment in the study. RESULTS: Overall 772 eligible patients (51.4 % males), mean age 56.7 (+/- 9.3) years, with mean diabetes duration 7.7 (+/- 5.5) years, mean duration of treatment with oral antidiabetic drugs 6.8 (+/- 4.9) years, and body mass index 37.6 (+/- 5.9) kg/m2 were enrolled in the study. Overall, 93.6 % were obese, 86.3 % subject were treated for hypertension, and 76.0 % for dyslipidemia. In total 96.1 % of patients completed the 6 months therapy. Lixisenatide significantly reduced HbA1c (decrease by 9.7 +/- 14.4 mmol/mol [3.1 +/- 0.2 % DCCT] after 6 months in per protocol population), and body weight (decrease by 3.5 +/- 5.4 kg). The best responders to the treatment were younger patients with higher BMI, who had a shorter duration of diabetes. Overall safety profile of lixisenatide was satisfactory in the study. The most frequent adverse events were functional disorders affecting the gastrointestinal system. There was no episode of severe hypoglycemia reported throughout the study. CONCLUSION: In a real-life practice cohort of patients with type 2 diabetes mellitus 6 months treatment with once-daily GLP1 receptor agonist lixisenatide significantly improved glucose control and decreased body weight without increasing the risk of symptomatic and/or severe hypoglycemia risk. FUNDING: Sanofi Czech Republic.Key words: GLP1 receptor agonist - glycated hemoglobin - HbA1c - lixisenatide - oral antidiabetic drugs (OAD) - observational study - hypoglycemia - type 2 diabetes mellitus. PMID- 29791171 TI - [Diagnosis of MODY - brief overview for clinical practice]. AB - Maturity Onset Diabetes of the Young (MODY) comprises inherited forms of diabetes mellitus caused by the mutations in the genes involved in the development, differentiation and function of beta-cells. The majority of patients with MODY remains misdiagnosed and erroneously classified as type 1 or type 2 diabetic patients. Correct MODY diagnosis is, however, essential since it enables individualization of treatment, assessment of the prognosis and identification of diabetes among patient's relatives. Clinical presentation of MODY is highly variable and it could resemble other types of diabetes, thus identification of MODY patients might be difficult. In this review, we describe typical clinical presentation of the most common MODY subtypes, we summarize current diagnostic guidelines in confirmation of MODY and we raise the question of possible need for extension of current clinical criteria indicating a patient for molecular-genetic testing.Key words: clinical course - diagnosis - differential diagnosis - glucokinase - hepatocyte nuclear factors - MODY. PMID- 29791172 TI - [Current treatment options in Maturity-Onset Diabetes of the Young]. AB - The discovery of MODY (Maturity-Onset Diabetes of the Young) and the elucidation of its heritability enabled more precise clinical characteristics of different MODY subtypes and led to understanding that glucokinase MODY (GCK-MODY) is not associated with vascular complications in long term follow-up, whereas MODY of transcription factors (e.g. HNF1A-MODY) is in case of bad metabolic control connected with the acceleration of particularly microvascular complications. There is a strong evidence of the needlessness of any specific antidiabetic treatment in prognosticaly favourable GCK-MODY (except for the pregnancy). On the contrary, in MODY of transcription factors, including the most common one - HNF1A MODY, the treatment, traditionally based on sulphonylurea derivatives (and after their failure on insulin) is required. Due to wider spectrum of available antidiabetic agents offering individualization of the treatment, the question of efficacy of other antidiabetic agents in MODY patients arises. This review article summarizes current knowledge of therapeutic options in patients with MODY.Key words: insulin - MODY - oral hypoglycemic drugs - treatment. PMID- 29791173 TI - [Rotational thromboelastometry in therapy of life threatening bleeding]. AB - Bleeding and coagulopathy is a common problem in the fields of internal medicine. In case of life-threatening bleeding, rotational thromboelastometry (ROTEM) has critical role in diagnosis and therapy of coagulopathy. In contrast to commonly used tests such as prothrombin time and activated partial thromboplastin time, ROTEM evaluates coagulation of the whole blood as a bedside method. The use of ROTEM for rapid diagnosis and targeted therapy of coagulopathy leads to reduction in bleeding and thus to reduction in administration of blood transfusion products. ROTEM is a viscoelastic method incorporated in current European and Czech-Slovak guidelines for managing life-threatening bleeding. In this article, we provide the reader with information on the method and also a simple scheme for the treatment of coagulopathy guided by ROTEM.Key words: bleeding - coagulopathy thromboelastometry. PMID- 29791174 TI - [Drug and herbal hepatotoxicity: an overview of clinical classifications]. AB - Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests. Laboratory tests may be helpful to specify immunopathogenetic origin, but negative results does not exclude diagnosis. The exclusion of other possible etiological factors is the crucial condition of diagnosis statement. Key words: DILI/drug induced liver toxicity - DILIn network - RUCAM classification. PMID- 29791175 TI - [Dyslipidemia and hypertension - what to worry about more?] AB - Dyslipidemia is present in every other patient with arterial hypertension. With increasing blood pressure and cholesterol levels, the risk of cardiovascular events increases proportionally. Treatment of dyslipidemia appears to lower cardiovascular mortality to a greater extent than treatment of hypertension. A significant proportion of patients with dyslipidemia indicated for drug therapy are not treated at all or treated insufficiently and do not reach the target values. Concurrent treatment of hypertension and dyslipidemia reduces the incidence of cardiovascular events significantly more than treating only one of these diseases. An even better efficacy of combined treatment of hypertension and dyslipidemia can be achieved by improving patient adherence using fixed drug combinations.Key words: arterial hypertension - cardiovascular events - dyslipidemia - fixed combinations -treatment. PMID- 29791176 TI - [A consensual therapeutic recommendation for type 2 diabetes mellitus by the Slovak Diabetes Society (2018)]. AB - Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.Key words: biguanides - gliflozins - gliptins - glitazones - GLP-1-receptor agonists - insulin - sulfonylurea. PMID- 29791177 TI - [Acquired hemophilia A: case report]. AB - Case report of a 74-year-old male with acquired hemophilia A, whose etiology was not found, confirmed by hemocoagulation examinations, with clinical manifestation of protracted macroscopic hematuria, spontaneous skin and intramuscular bleedings. Treatment comprised conservative therapy administration of hemostyptics, red blood cells transfusions application of recombinant human factor VII (rFVII) and immunosuppression. Finally, patient died due to nosocomial infection caused by multidrug-resistant pulmonary pathogen.Key words: acquired hemophilia A - bleeding. PMID- 29791178 TI - [Rare combination of Turner syndrome and congenital adrenal hyperplasia with 21 hydroxylase deficiency: case report]. AB - Combination of Turner syndrome (TS) and classic congenital adrenal hyperplasia (CAH) is rare. Globally, the incidence of CAH, autosomal recessive disorder caused by enzyme defect of steroidogenic pathway, is very low (1 : 10 000-16 000). 90 % of CAH cases are caused by 21-hydroxylase gene mutation (CYP21A2). Globally, the incidencie of Turner syndrome reaches 1 : 2 500. Phenotypically, females with TS may render wide spectrum of clinical features. Dominant symptoms are lowered terminal height and gonadal dysgenesia, ultimately leading to absence of puberty and infertility. Virilisation may be evident among TS women with chromosome Y 45, X/46, XY. We present a 57 year old woman suffering from both TS 45, X/46, XX and 21-hydroxylase deficiency. Based on the intersex, she was misdiagnosed as a male after the birth. Dominant signs were intrauterine growth retardation and Prader 5 virilisation of the external genitalia. Testes were not palpable. Laparoscopy at the age of 6 showed uterus and ovaries. After this examination, clitoroplasty and vaginoplasty was performed. Karyotyping revealed a 45, X/46, XX pattern. The presence of virilising features at the time of puberty however could not be explained with the diagnosis of Turner syndrome. Laboratory tests revealed elevated level of 17-hydroxyprogesterone, dehydroepiandrosterone with low cortisol concentration and elevated ACTH. With the genomic analysis CYP21A2 gene, namely IN2G (IVS 2-13 A/C>G), large deletion/conversion was detected. Glucocorticoid treatment was initiated. Due to increased plasma renin concentration, fludrocortisone therapy was also initiated. Within this therapy, patient's state improved significantly.Key words: congenital adrenal hyperplasia CYP21A2 - Turner syndrome - 21-hydroxylase deficiency. PMID- 29791179 TI - [Virilization as demonstration of hypertestosteronism by ovarian tumor: case report]. AB - Hypertestosteronism as part of hyperandrogenic states in women is generally defined as abundance of male hormones (in this case abundance of testosterone). Spectrum of clinical symptoms include menstrual disorders, amenorrhoea, different range of hirsutism and virilization. Statistically, most androgen secreting tumors are ovarian aetiology (testosterone secreting tumors located in suprarenal gland are very rare). This rare tumor may produce excess amounts of testosterone, as well as its precursor androstenedione. The highest incidence is between 20-40 years and in postmenopausal period. The treatment is essentially surgical; with gradual adjustment of the hormones.Key words: androgen secreting ovarian tumors - hyperandrogenic states - testosterone - virilisation. PMID- 29791180 TI - [Heart transplantation and follow-up treatment with AL-amyloidosis in 5 patients]. AB - The prognosis for patients with cardiac impairment due to AL-amyloid deposition and severe cardiac insufficiency is poor, with a survival median in the order of months. The classical treatment of AL-amyloidosis in combination with cardiac insufficiency is very poorly tolerated and the treatment of such patients is associated with considerably higher mortality than among other patients with AL amyloidosis. If, however, patients with an isolated or another dominating cardiac impairment, without severe damage to other organs and tissues, have a heart transplant performed, their cardiovascular condition will significantly improve as a result, along with their ability to tolerate any kind of treatment for AL amyloidosis including that using high-dose chemotherapy with a transplant of autologous hematopoietic stem cells. The achievement of complete remission of AL amyloidosis is a precondition for long-term survival, since when not achieved, amyloid deposition also arises in the transplanted heart. At the Centre for Cardiovascular and Transplantation Surgery, Brno, the first heart transplant due to its impairment by AL-amyloidosis was performed in 2010. By the year 2017 the number of patients with AL-amyloidosis, who had first undergone a heart transplant with subsequent treatment for AL-amyloidosis, increased to 5. The median age at which a heart transplant was performed is 60 (48-65) years. Four patients were men, one was a woman. The median monitoring equals 65 (88-15) months. Complete remission of AL-amyloidosis was achieved in all the patients. There were 5 lines of treatment needed for the first patient to attain it, of that twice high-dose melphalan with autologous stem cell transplantation, for the second patient a second-line treatment, high-dose melphalan and bortezomib-based therapy. No specific therapy was needed for the third patient, as immunosuppressive therapy following the heart transplant containing prednison led to complete remission of AL-amyloidosis. In the fourth case, sustainable complete remission was reached by high-dose melphalan and in the fifth case by one line of bortezomib-based therapy. The aforementioned data illustrate that a heart transplant is the first step which makes the patients with a severe heart failure, not tolerating any efficient therapy of AL-amyloidosis, capable of undergoing intense treatment of AL-amyloidosis. Sometimes one high-dose chemotherapy is sufficient, while at other times multiple treatment lines are needed to reach complete remission of AL-amyloidosis.Key words: AL-amyloidosis - autologous hematopoietic stem cells transplantation - bortezomib - cardiomyopathy - lenalidomide - thalidomide - heart transplantation. PMID- 29791181 TI - [Cyclic Cushings syndrome: a case study and overview]. AB - Cushings syndrome and especially Cushing's disease represent diagnostically and therapeutically complicated medical situations. In some patients, cyclic changes in cortisol production additionally hamper the diagnosis in terms of source identification and management of hormone overproduction. It may not be clear, whether the patient is cured or not even years after the treatment. It is a rare disorder variant, but we assume that it is underdiagnosed and it's incidence is actually higher. The article deals with a complicated course of diagnosis and treatment in a patient with cyclic Cushings syndrome.Key words: Cushing's disease - cyclic Cushing's syndrome - hypercortisolism. PMID- 29791182 TI - Season-Ending Shoulder Injuries in the National Collegiate Athletic Association: Data From the NCAA Injury Surveillance Program, 2009-2010 Through 2013-2014. AB - BACKGROUND: Examination of the incidence of shoulder season-ending injury (SEI) in the collegiate athlete population is limited. PURPOSE: To determine the incidence of shoulder SEI in the National Collegiate Athletic Association (NCAA) and to investigate the risk factors for a shoulder injury ending an athlete's season. STUDY DESIGN: Descriptive epidemiology study. METHODS: All shoulder injuries from the NCAA Injury Surveillance Program database for the years 2009 2010 to 2013-2014 were extracted, and SEI status was noted. The incidences of SEI and non-SEI were calculated for athlete, activity, and injury characteristics and compared via univariable analysis and risk ratios to determine risk factors for an injury being season ending. RESULTS: Shoulder injuries were season ending in 4.3% of cases. The overall incidence of shoulder SEI was 0.31 per 10,000 athlete exposures (AEs), as opposed to 7.25 per 10,000 AEs for all shoulder injuries. Shoulder instability constituted 49.1% of SEI, with an incidence of 0.15 per 10,000 AEs, while fractures had the highest rate of being season ending (41.9%). Men's wrestling had the highest incidence of shoulder SEI (1.65 per 10,000 AEs), while men's soccer had the highest proportion of shoulder injuries that ended a season (14.6%). Overall, men had a 6.3-fold higher incidence of SEI than women and a 2.4-fold increased likelihood that an injury would be season ending. CONCLUSION: Injury to the shoulder of an NCAA athlete, while somewhat infrequent, can have significant implications on time lost from play. Incidence of these injuries varies widely by sport and injury, with a number of associated risk factors. Athletes sustaining potentially season-ending shoulder injuries, with their coaches and medical providers, may benefit from these data to best manage expectations and outcomes. PMID- 29791183 TI - A 2-Year Prospective Cohort Study of Overuse Running Injuries: The Runners and Injury Longitudinal Study (TRAILS). AB - BACKGROUND: The National Center for Injury Prevention and Control, noting flaws in previous running injury research, called for more rigorous prospective designs and comprehensive analyses to define the origin of running injuries. PURPOSE: To determine the risk factors that differentiate recreational runners who remain uninjured from those diagnosed with an overuse running injury during a 2-year observational period. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Inclusion criteria were running a minimum of 5 miles per week and being injury free for at least the past 6 months. Data were collected at baseline on training, medical and injury histories, demographics, anthropometrics, strength, gait biomechanics, and psychosocial variables. Injuries occurring over the 2-year observation period were diagnosed by an orthopaedic surgeon on the basis of predetermined definitions. RESULTS: Of the 300 runners who entered the study, 199 (66%) sustained at least 1 injury, including 73% of women and 62% of men. Of the injured runners, 111 (56%) sustained injuries more than once. In bivariate analyses, significant ( P <= .05) factors at baseline that predicted injury were as follows: Short Form Health Survey-12 mental component score (lower mental health-related quality of life), Positive and Negative Affect Scale negative affect score (more negative emotions), sex (higher percentage of women were injured), and knee stiffness (greater stiffness was associated with injury); subsequently, knee stiffness was the lone significant predictor of injury (odds ratio = 1.18) in a multivariable analysis. Flexibility, quadriceps angle, arch height, rearfoot motion, strength, footwear, and previous injury were not significant risk factors for injury. CONCLUSION: The results of this study indicate the following: (1) among recreational runners, women sustain injuries at a higher rate than men; (2) greater knee stiffness, more common in runners with higher body weights (>=80 kg), significantly increases the odds of sustaining an overuse running injury; and (3) contrary to several long-held beliefs, flexibility, arch height, quadriceps angle, rearfoot motion, lower extremity strength, weekly mileage, footwear, and previous injury are not significant etiologic factors across all overuse running injuries. PMID- 29791185 TI - Safety of Ibuprofen for Postoperative Pain After Palatoplasty: A Pilot Study. AB - OBJECTIVE: To determine the safety of ibuprofen used for postoperative pain control following palatoplasty in pediatric patients. DESIGN: Retrospective chart review. SETTING: Tertiary care, pediatric hospital. PARTICIPANTS: Patients who received ibuprofen for postoperative pain control after palatoplasty. MAIN OUTCOME MEASURES: Number of doses of ibuprofen given during hospitalization and the presence of postoperative primary or secondary bleeding following palatoplasty. Detection of postoperative hemorrhage was obtained from (1) chart review from inpatient hospitalization after palatoplasty, (2) chart review of each patient's 3-week postoperative clinic visit, and (3) phone call to caretakers from primary author. RESULTS: Thirty-two patients underwent palatoplasty who received ibuprofen for control of postoperative pain. Mean number of inpatient doses given was 4.8 (range: 1-17). None (0%) experienced hemorrhage in the hospital before discharge. Thirty-two (100%) patients were seen at a 3-week follow-up and no (0%) episodes of postoperative hemorrhage were noted. Seventeen (53%) caretakers of patients responded to contact by phone and confirmed no subsequent bleeding. CONCLUSIONS: Ibuprofen may not increase postoperative hemorrhage after palatoplasty. Further studies will be needed to evaluate safety on a larger scale. PMID- 29791186 TI - Markedly Elevated Intracranial Pressure Treated With Cranial Vault Expansion, Instead of CSF Shunting, in a Child With Hurler-Scheie Syndrome and Multiple Suture Craniosynostosis. AB - Despite a known association of mucopolysaccharidoses (MPS) and craniosynostosis, treatment of elevated intracranial pressure (ICP) in these patients is primarily cerebrospinal fluid (CSF) shunting. We present a unique case of Hurler-Scheie syndrome with multisuture craniosynostosis and elevated ICP, without ventriculomegaly, where elevated ICP was successfully treated with extensive cranial vault expansion and shunt placement was avoided. Patients with MPS should be evaluated for craniosynostosis, and calvarial vault expansion may be considered as a viable treatment alternative to CSF shunting for elevated ICP in select patients. PMID- 29791187 TI - A Single Lab Test to Aid Pierre Robin Sequence Severity Diagnosis. AB - OBJECTIVE: The workup of patients with Pierre Robin sequence (PRS) consists of a physical examination, O2 saturation, and polysomnography to determine the severity of respiratory obstruction and need for surgery. We suggest that capillary blood gas (CBG) may be a better physiologic representation of airway obstruction and should be routinely used in the management of patients with PRS. DESIGN: This is a multicenter study based on a retrospective review of medical records. SETTING: The study was performed at tertiary care centers. INTERVENTIONS: Patients with PRS <1 year old underwent mandibular distraction osteogenesis. MAIN OUTCOME MEASURE: Using successful treatment outcome as a reference standard, receiver operating characteristic (ROC) curve was used to determine the accuracy of the diagnostic test and values for the best sensitivity and specificity to determine the need for surgical intervention. RESULTS: Of 73 patients, 48 had sporadic PRS, 23 had syndromes, 2 had micrognathia, not otherwise specified. Mandibular distraction osteogenesis was performed in 62 patients at a mean age of 39 days. The mean initial Apnea-Hypopnea Index (AHI) in nonsurgical versus surgical groups was 10 versus 31 ( P = .063), pH 7.41 versus 7.34 ( P = .003), pCO2 43 versus 56 ( P < .001), and HCO3 27 versus 30 ( P = .022). The ROC curve showed that pCO2 of 49.5 has the best specificity (100%) and sensitivity (72.6%) profile in terms of need for definitive airway. CONCLUSION: A simple CBG heel stick may better predict the physiologic effects of obstructive apnea; therefore, it should be added to the algorithm of PRS workup. PMID- 29791188 TI - The Effects of Cognitive and Visual Workload on Peripheral Detection in the Detection Response Task. AB - OBJECTIVE: The independent effects of cognitive and visual load on visual Detection Response Task (vDRT) reaction times were studied in a driving simulator by performing a backwards counting task and a simple driving task that required continuous focused visual attention to the forward view of the road. The study aimed to unravel the attentional processes underlying the Detection Response Task effects. BACKGROUND: The claim of previous studies that performance degradation on the vDRT is due to a general interference instead of visual tunneling was challenged in this experiment. METHOD: vDRT stimulus eccentricity and stimulus conspicuity were applied as within-subject factors. RESULTS: Increased cognitive load and visual load both resulted in increased response times (RTs) on the vDRT. Cognitive load increased RT but revealed no task by stimulus eccentricity interaction. However, effects of visual load on RT showed a strong task by stimulus eccentricity interaction under conditions of low stimulus conspicuity. Also, more experienced drivers performed better on the vDRT while driving. CONCLUSION: This was seen as evidence for a differential effect of cognitive and visual workload. The results supported the tunnel vision model for visual workload, where the sensitivity of the peripheral visual field reduced as a function of visual load. However, the results supported the general interference model for cognitive workload. APPLICATION: This has implications for the diagnosticity of the vDRT: The pattern of results differentiated between visual task load and cognitive task load. It also has implications for theory development and workload measurement for different types of tasks. PMID- 29791184 TI - A Narrative Review of Medical and Genetic Risk Factors among Children Age 5 and Younger with Severe Obesity. AB - Severe obesity defined as an age- and gender-specific body mass index >=120% of the 95th percentile in children younger than 5 years is well recognized as a significant challenge for prevention and treatment. This article provides an overview of the prevalence, classification of obesity severity, patterns of weight gain trajectory, medical and genetic risk factors, and comorbid disorders among young children with an emphasis on severe obesity. Studies suggest rapid weight gain trajectory in infancy, maternal smoking, maternal gestational diabetes, and genetic conditions are associated with an increased risk for severe obesity in early childhood. Among populations of young children with severe obesity seeking care, co-morbid conditions such as dyslipidemia and fatty liver disease are present and families report behavioral concerns and developmental delays. Children with severe obesity by age 5 represent a vulnerable population of children at high medical risk and need to be identified early and appropriately managed. PMID- 29791189 TI - Late-onset stress symptomatology (LOSS) scale - short form: development and validation. AB - OBJECTIVES: Late-onset stress symptomatology (LOSS) is a phenomenon observed in older combat veterans who experience increased combat-related thoughts, feelings, and reminiscences corresponding with the changes and challenges of aging. Previously, we developed the LOSS Scale to assess LOSS. This paper describes the development and validation of a LOSS Scale short form (LOSS-SF) to screen veterans in various settings who may be actively re-examining their past wartime experiences. METHOD: Three studies examined the reliability and validity of the LOSS-SF in separate samples of male combat veterans age 55 and older (total N = 346). Veterans were administered measures via telephone and mail survey. Correlation and regression analyses examined the reliability and validity of the LOSS-SF. RESULTS: The LOSS-SF exhibited strong internal consistency (alpha = .93), test-retest reliability (2 week interval on average; r = .88), and good concurrent validity with the LOSS Scale (r = .81). Convergent and divergent validity were supported by the pattern of correlations between the LOSS-SF and other construct measures. CONCLUSION: The LOSS-SF is a reliable and valid measure to quickly assess thoughts, feelings, and reminiscences about past combat experiences in older veterans and identify those veterans in distress who may benefit from psychological interventions.. PMID- 29791190 TI - The Comprehensive Primary Care Initiative: Effects On Spending, Quality, Patients, And Physicians. AB - The Comprehensive Primary Care Initiative (CPC), a health care delivery model developed by the Centers for Medicare and Medicaid Services (CMS), tested whether multipayer support of 502 primary care practices across the country would improve primary care delivery, improve care quality, or reduce spending. We evaluated the initiative's effects on care delivery and outcomes for fee-for-service Medicare beneficiaries attributed to initiative practices, relative to those attributed to matched comparison practices. CPC practices reported improvements in primary care delivery, including care management for high-risk patients, enhanced access, and improved coordination of care transitions. The initiative slowed growth in emergency department visits by 2 percent in CPC practices, relative to comparison practices. However, it did not reduce Medicare spending enough to cover care management fees or appreciably improve physician or beneficiary experience or practice performance on a limited set of Medicare claims-based quality measures. As CMS and other payers increasingly use alternative payment models that reward quality and value, CPC provides important lessons about supporting practices in transforming care. PMID- 29791191 TI - Effects of Bone Incorporation After Arthroscopic Stabilization Surgery for Bony Bankart Lesion Based on Preoperative Glenoid Defect Size. AB - BACKGROUND: Recurrent shoulder instability occurs more frequently after soft tissue surgery when the glenoid defect is greater than 20%. However, for lesions less than 20%, no scientific guidance is available regarding what size of bone fragments may affect shoulder functional restoration after bone incorporation. Purpose/Hypothesis: The purpose was to analyze how preoperative glenoid defect size and bone fragment incorporation alter postoperative clinical outcomes, we compared the functional outcomes of shoulders with and without bony Bankart lesion. It was hypothesized that differences in postoperative clinical outcomes between patients with and without bony fragments would be found only in patients with a larger glenoid defect. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 223 patients who underwent arthroscopic stabilization surgery for recurrent anterior shoulder instability were divided into two groups based on the presence of anterior glenoid bone fragments. In each group, postoperative shoulder functional outcomes, sports activity level, and recurrence rates were evaluated according to preoperative glenoid defect size (small, <10%; medium, 10% 15% and 15%-20%; large, >20%). RESULTS: In patients with small or medium defects, no significant differences were found in postoperative clinical outcomes and sports activity levels between the two groups. However, in patients with a large defect, the patients with bone fragments (mean +/- SD American Shoulder and Elbow Surgeons [ASES] score, 92.3 +/- 2.7; Rowe score, 90.9 +/- 5.4) showed significantly superior clinical outcomes compared with patients who did not have fragments (ASES score, 87.3 +/- 6.2, P = .02; Rowe score, 84.8 +/- 7.3, P = .04). Among patients without bone fragments, recurrence increased significantly with increasing preoperative glenoid defect size (recurrence rates: 0% in small defects, 7.4% in medium defects, 22.2% in large defects), whereas patients with bone fragments showed no tendency for increasing or decreasing recurrence rates (0% in small defects, 7.9% in medium defects, 5.9% in large defects). CONCLUSION: In the treatment of bony Bankart lesion, the effect of bone fragment incorporation was different according to preoperative glenoid defect size. In patients with preoperative glenoid defects less than 20% of the glenoid width, bone fragment incorporation after arthroscopic bony Bankart repair did not alter clinical outcomes, sports activity levels, or recurrence rates, whereas in patients with defects greater than 20% of the glenoid width, bone fragment incorporation improved clinical outcomes and recurrence rates. PMID- 29791192 TI - Perceived pubertal timing and borderline personality pathology in female adolescent inpatients. AB - Borderline personality pathology typically onsets during adolescence. An important consideration in understanding adolescent psychopathology is pubertal development. Perceived pubertal timing is one facet of puberty that is especially relevant to adolescent psychopathology, especially when timing is perceived to be early. Despite links between early pubertal timing and core features of borderline personality disorder, and between early pubertal timing and disruptions in the interpersonal context, perceived pubertal timing has yet to be studied in relation to adolescent borderline pathology. This preliminary study aimed to test the association between perceived pubertal timing and borderline symptoms in adolescent girls, controlling for internalizing and externalizing pathology. Forty-two female adolescent inpatients (ages 12-15, Mage = 14.02, 81% White) completed measures of perceived pubertal development and borderline symptoms and a diagnostic interview. Results indicated that earlier perceived pubertal timing was uniquely associated with higher borderline symptoms even when internalizing and externalizing disorders were covaried. PMID- 29791193 TI - Shame and interpersonal sensitivity: Gender differences and the association between internalized shame coping strategies and interpersonal sensitivity. AB - The present study investigated gender differences in interpersonal sensitivity and internalized shame coping strategies in 252 undergraduate students. To measure interpersonal sensitivity and shame coping strategies, the self assessment forms Interpersonal Sensitivity Measure and Compass of Shame Scale were used. The analyses revealed that compared to men, women display interpersonal sensitivity to a higher degree, and they use internalized shame coping strategies to a greater extent. The results also showed that interpersonal sensitivity is highly correlated with shame coping strategies. However, in contrast to earlier research, no gender difference was found, and gender did not significantly mediate the association between interpersonal sensitivity and internalized shame coping. These results could aid clinicians and researchers in promoting, designing, delivering, and evaluating treatments for patients with, for example, depression, anxiety, and interpersonal and/or relational problems. PMID- 29791194 TI - Word count as an indicator of suicide risk in an inpatient setting. AB - The current study replicates a previously used methodology with a suicidal inpatient sample regarding word counts generated by participants writing about suicidal constructs. Word counts (i.e., the number of written words) on the Suicide Status Form from initial sessions with suicidal inpatients were compared to self-rated suicide risk scores as well as to continuous and repeated measures of hopelessness and suicide ideation assessed over the course of inpatient care. Results showed that higher word counts were associated with initially higher suicide ideation scores that steadily declined over the course of treatment. Lower word counts were associated with lower initial hopelessness scores that increased during treatment before ultimately decreasing. In addition, word count was not found to be a significant predictor of self-rated suicide risk. Clinical implications of these data and future directions are discussed. PMID- 29791196 TI - Determining Success or Failure After Foot and Ankle Surgery Using Patient Acceptable Symptom State (PASS) and Patient Reported Outcome Information System (PROMIS). AB - BACKGROUND: As the role of generic patient-reported outcomes (PROs) expands, important questions remain about their interpretation. In particular, how the Patient Reported Outcome Measurement Instrumentation System (PROMIS) t score values correlate with the patients' perception of success or failure (S/F) of their surgery is unknown. The purposes of this study were to characterize the association of PROMIS t scores, the patients' perception of their symptoms (patient acceptable symptom state [PASS]), and determination of S/F after surgery. METHODS: This retrospective cohort study contacted patients after the 4 most common foot and ankle surgeries at a tertiary academic medical center (n = 88). Patient outcome as determined by phone interviews included PASS and patients' judgment of whether their surgery was a S/F. Assessment also included PROMIS physical function (PF), pain interference (PI), and depression (D) scales. The association between S/F and PASS outcomes was evaluated by chi-square analysis. A 2-way analysis of variance (ANOVA) evaluated the ability of PROMIS to discriminate PASS and/or S/F outcomes. Receiver operator curve (ROC) analysis was used to evaluate the ability of pre- (n = 63) and postoperative (n = 88) PROMIS scores to predict patient outcomes (S/F and PASS). Finally, the proportion of individuals classified by the identified thresholds were evaluated using chi square analysis. RESULTS: There was a strong association between PASS and S/F after surgery (chi-square <0.01). Two-way ANOVA demonstrated that PROMIS t scores discriminate whether patients experienced positive or negative outcome for PASS ( P < .001) and S/F ( P < .001). The ROC analysis showed significant accuracy (area under the curve > 0.7) for postoperative but not preoperative PROMIS t scores in determining patient outcome for both PASS and S/F. The proportion of patients classified by applying the ROC analysis thresholds using PROMIS varied from 43.0% to 58.8 % for PASS and S/F. CONCLUSIONS: Patients who found their symptoms and activity at a satisfactory level (ie, PASS yes) also considered their surgery a success. However, patients who did not consider their symptoms and activity at a satisfactory level did not consistently consider their surgery a failure. PROMIS t scores for physical function and pain demonstrated the ability to discriminate and accurately predict patient outcome after foot and ankle surgery for 43.0% to 58.8% of participants. These data improve the clinical utility of PROMIS scales by suggesting thresholds for positive and negative patient outcomes independent of other factors. LEVEL OF EVIDENCE: II, prospective comparative series. PMID- 29791195 TI - Psychometric evaluation of the Inventory of Interpersonal Problems 32. AB - The Inventory of Interpersonal Problems 32 (IIP-32; Horowitz, Aiden, Wiggins, & Pincus, 2000) is a brief, 32-item, self-report questionnaire used to screen for interpersonal problems. While studies of the IIP-32's psychometric properties have been conducted in other nations, and studies have examined the psychometric properties of the IIP-32's circumplex structure, no studies have examined the factor-analytic structure in the United States since the original standardization sample. The aim of this study was to examine the psychometric properties of the IIP-32 in American college women for the first time and explore its structural validity as a circumplex measure and its concurrent validity with measures of attachment. The current study found that internal consistency estimates and interscale correlations were generally high and confirmed the proposed circumplex structure. In addition, concurrent validity was evidenced by confirming theorized relations between attachment and the IIP-32 subscales. However, IIP-32 subscales were limited with regard to divergent validity. PMID- 29791197 TI - Gender differences in psychosocial determinants of self-perceived health among Portuguese older adults in nursing homes. AB - OBJECTIVES: Self-perceived health declines with age, varies by gender and is a predictor of mortality, morbidity, physical and psychological functioning. However, gender differences in health and illness perception are complex and not yet fully understood. This study aimed to explore gender-related differences in psychosocial determinants of self-perceived health among older adults living in nursing homes. METHOD: Nationwide face-to-face survey of the Portuguese population aged 65 and over. A representative sample of nursing homes residents was obtained through a multistage cluster random sampling of nursing homes, stratified by main Portuguese administrative regions (NUTS II). RESULTS: Overall, 1186 nursing homes residents voluntarily enrolled in this study (participation rate, 93%) and a total of 515 participants (70.1% women) were considered to have adequate cognitive functioning to answer all questionnaires. A significant association between self-rated health and gender was found: 90.6% of all women (95% CI: 85.7-93.9) and 82.3% of all men (95% CI: 72.9-88.9) rated their health as less than good (p = 0.023). Gender-stratified analyses showed differences in psychosocial determinants of self-perceived health. While symptoms of depression and loneliness feelings were the major psychosocial determinants of poor self perceived health among women, age and subjective financial well-being were the only determinants among men. CONCLUSION: Factors associated with perceived health, as representative of healthy ageing, were identified by gender, leading to future avenues for fruitful investigation. The acknowledgement of interpersonal and socioeconomic factors that determine the experience of ageing at a national level is crucial to improve the health of elders. PMID- 29791198 TI - Updates on ultrasound research in implant dentistry: a systematic review of potential clinical indications. AB - OBJECTIVES: Ultrasonography has shown promising diagnostic value in dental implant imaging research; however, exactly how ultrasound was used and at what stage of implant therapy it can be applied has not been systematically evaluated. Therefore, the aim of this review is to investigate potential indications of ultrasound use in the three implant treatment phases, namely planning, intraoperative and post-operative phase. METHODS: Eligible manuscripts were searched in major databases with a combination of keywords related to the use of ultrasound imaging in implant therapy. An initial search yielded 414 articles, after further review, 28 articles were finally included for this systematic review. RESULTS: Ultrasound was found valuable, though at various development stages, for evaluating (1) soft tissues, (2) hard tissues (3) vital structures and (4) implant stability. B-mode, the main function to image anatomical structures of interest, has been evaluated in pre-clinical and clinical studies. Quantitative ultrasound parameters, e.g. sound speed and amplitude, are being developed to evaluate implant-bone stability, mainly in simulation and pre clinical studies. Ultrasound could be potentially useful in all three treatment phases. In the planning phase, ultrasound could evaluate vital structures, tissue biotype, ridge width/density, and cortical bone thickness. During surgery, it can provide feedback by identifying vital structures and bone boundary. At follow-up visits, it could evaluate marginal bone level and implant stability. CONCLUSIONS: Understanding the current status of ultrasound imaging research for implant therapy would be extremely beneficial for accelerating translational research and its use in dental clinics. PMID- 29791199 TI - Localization of the inferior alveolar canal using ultralow dose CT with iterative reconstruction techniques. AB - OBJECTIVES:: To compare subjective and objective localization of the inferior alveolar canal (IAC) on multidetector CT (MDCT) images obtained by ultralow doses in combination with the reconstruction techniques of filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASIR), or model-based iterative reconstruction (MBIR) as compared to standard dose MDCT and FBP. METHODS:: Three cadavers were imaged with a reference standard dose MDCT examination (volume CT dose index: 29.4 mGy) reconstructed with FBP and 5 low dose protocols (LD1-5) (volumeCT dose index: 4.19, 2.64, 0.99, 0.53, 0.29 mGy) reconstructed with FBP, ASIR 50, ASIR 100, and MBIR. Linear measurements from the crest of the ridge to the roof of the IAC were recorded. The results from the test protocols were compared with those from the reference using Bland-Altman plots. RESULTS:: Only three test protocols allowed the identification of the position of the IAC on all the sample sites: LD1/FBP and LD1/ASIR 100 and LD2/FBP. All three protocols allowed identification of the IAC with comparable results to the reference dose protocol; the 95% confidence interval limits for the measurement differences were +/- 0.41 mm, but the differences were not statistically significant. The calculated effective dose for the LD2 protocol, for a scan length of 5 cm, was 27.7 uSv. CONCLUSIONS:: Using FBP, comparable IAC measurements were achieved with 91% reduction in dose compared with a standard exposure protocol. The use of ASIR and MBIR did not improve identification of the IAC in MDCT low dose images. PMID- 29791201 TI - Performance of an Additional Task During Level 2 Automated Driving: An On-Road Study Comparing Drivers With and Without Experience With Partial Automation. AB - OBJECTIVE: To investigate the influence of prior experience with Level 2 automation on additional task performance during manual and Level 2 partially automated driving. BACKGROUND: Level 2 automation is now on the market, but its effects on driver behavior remain unclear. Based on previous studies, we could expect an increase in drivers' engagement in secondary tasks during Level 2 automated driving, but it is yet unknown how drivers will integrate all the ongoing demands in such situations. METHOD: Twenty-one drivers (12 without, 9 with Level 2 automation experience) drove on a highway manually and with Level 2 automation (exemplified by Volvo Pilot Assist generation 2; PA2) while performing an additional task. In half of the conditions, the task could be interrupted (self-paced), and in the other half, it could not (system-paced). Drivers' visual attention, additional task performance, and other compensatory strategies were analyzed. RESULTS: Driving with PA2 led to decreased scores in the additional task and more visual attention to the dashboard. In the self-paced condition, all drivers looked more to the task and perceived a lower mental demand. The drivers experienced with PA2 used the system and the task more than the novice group and performed more overtakings. CONCLUSIONS: The additional task interfered more with Level 2 automation than with manual driving. The drivers, particularly the automation novice drivers, used some compensatory strategies. APPLICATIONS: Automation designers need to consider these potential effects in the development of future automated systems. PMID- 29791200 TI - Evaluation of mandibular odontogenic keratocyst and ameloblastoma by panoramic radiograph and computed tomography. AB - OBJECTIVES:: The purpose of this study was to describe and compare the main imagenological features of mandibular ameloblastomas and odontogenic keratocyst (OKC) using panoramic radiograph (PR) and CT. METHODS:: The sample consisted of nine cases of ameloblastomas and nine cases of OKC. PR and CT images were analyzed according to shape, internal structure, borders, associated unerupted tooth, root resorption, expansion and perforation of cortical bones. RESULTS:: PR evaluation allowed the identification of the lesion's location, presence of sclerosis in the periphery, presence of associated non-erupted tooth and expansion of the mandible's lower border cortical bone. CT was more accurate than PR in the assessment of the lesion shape, presence of inner bone septa, root resorption, buccolingual expansion and rupture of cortical bone. Most cases of ameloblastoma and OKC presented buccolingual expansion and erosion of cortical bone. Only ameloblastomas showed tooth root resorption. CONCLUSIONS:: Although PR is very helpful and widely used, CT provides more precise information on buccolingual expansion, calcification, bone septa, perforation of cortical bones and tooth resorption, features that are frequently underdescribed in the literature, particularly in OKC. PMID- 29791202 TI - Different MR features for differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma according to tumor size. AB - OBJECTIVE: To identify reliable magnetic resonance (MR) features for distinguishing mass-forming type of intrahepatic cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) based on tumor size. METHODS: This retrospective study included 395 patients with pathologically confirmed IMCCs (n = 180) and HCCs (n = 215) who underwent pre-operative contrast-enhanced MRI including diffusion-weighted imaging (DWI). MR features were evaluated and clinical data were also recorded. All the characteristics were compared in small (<=3 cm) and large tumor (>3 cm) groups by univariate analysis and subsequently calculated by multivariable logistic regression analysis. RESULTS: Multivariable analysis revealed that rim arterial phase hyperenhancement [odds ratios (ORs) = 13.16], biliary dilation (OR = 23.42) and CA19-9 (OR = 21.45) were significant predictors of large IMCCs (n = 138), and washout appearance (OR = 0.036), enhancing capsule appearance (OR = 0.039), fat in mass (OR = 0.057), chronic liver disease (OR = 0.088) and alpha fetoprotein (OR = 0.019) were more frequently found in large HCCs (n = 143). For small IMCCs (n = 42) and HCCs (n = 72), rim arterial phase hyperenhancement (OR = 9.68), target appearance at DWI (OR = 12.51), alpha fetoprotein (OR = 0.12) and sex (OR = 0.20) were independent predictors in multivariate analysis. CONCLUSION: Valuable MR features and clinical factors varied for differential diagnosis of IMCCs and HCCs according to tumor size. Advances in knowledge: MR features for differential diagnosis of large IMCC and HCC (>3 cm) are in keeping with that recommended by LI-RADS. However, for small IMCCs and HCCs (<=3 cm), only rim enhancement on arterial phase and target appearance at DWI are reliable predictors. PMID- 29791203 TI - Short-term thermoneutral housing alters glucose metabolism and markers of adipose tissue browning in response to a high-fat diet in lean mice. AB - Systemic insulin resistance and glucose intolerance occur with as little as 3 days of a high-fat diet (HFD) in mice and humans; the mechanisms that initiate acute insulin resistance are unknown. Most laboratories house mice at 22 degrees C, which is below their thermoneutral temperature (~30 degrees C). Cold stress has been shown to increase white adipose tissue (WAT) browning, alter lipid trafficking, and impair immune function, whereas energy intake and expenditure decrease with increasing ambient temperature; importantly, dysregulation of these parameters has been strongly linked to obesity-induced insulin resistance. Therefore, we compared acute changes in glucose metabolism and the metabolic phenotype in lean mice in response to a control diet or HFD housed at standard vivarium (22 degrees C) and thermoneutral (30 degrees C) temperatures. Glucose intolerance occurred following 1 or 5 days of HFD and was independent of housing temperature or adiposity; however, the reduction in tissue-specific glucose clearance with HFD diverged by temperature with reduced brown adipose tissue (BAT) glucose uptake at 22 degrees C but reduced soleus glucose uptake at 30 degrees C. Fasting glucose, food intake, and energy expenditure were significantly lower at 30 degrees C, independent of diet. Additionally, markers of browning in both BAT and inguinal subcutaneous WAT, but not perigonadal epididymal WAT, decreased at 30 degrees C. Together, we find housing temperature has a significant impact on the cellular pathways that regulate glucose tolerance in response to an acute HFD exposure. Thus, even short-term changes in housing temperature should be highly considered in interpretation of metabolic studies in mice. PMID- 29791204 TI - Role of adenosine signaling in coordinating cardiomyocyte function and coronary vascular growth in chronic fetal anemia. AB - Fetal anemia causes rapid and profound changes in cardiac structure and function, stimulating proliferation of the cardiac myocytes, expansion of the coronary vascular tree, and impairing early contraction and relaxation. Although hypoxia inducible factor-1alpha is sure to play a role, adenosine, a metabolic byproduct that increases coronary flow and growth, is implicated as a major stimulus for these adaptations. We hypothesized that genes involved in myocardial adenosine signaling would be upregulated in chronically anemic fetuses and that calcium handling genes would be downregulated. After sterile surgical instrumentation under anesthesia, gestationally timed fetal sheep were made anemic by isovolumetric hemorrhage for 1 wk (16% vs. 35% hematocrit). At 87% of gestation, necropsy was performed to collect heart tissue for PCR and immunohistochemical analysis. Anemia increased mRNA expression levels of adenosine receptors ADORA 1, ADORA2A, and ADORA2B in the left and right ventricles (adenosine receptor ADORA3 was unchanged). In both ventricles, anemia also increased expression of ectonucleoside triphosphate diphosphohydrolase 1 and ecto-5'-nucleotidase. The genes for both equilibrative nucleoside transporters 1 and 2 were expressed more abundantly in the anemic right ventricle but were not different in the left ventricle. Neither adenosine deaminase nor adenosine kinase cardiac levels were significantly changed by chronic fetal anemia. Chronic fetal anemia did not significantly change cardiac mRNA expression levels of the voltage-dependent L type calcium channel, ryanodine receptor 1, sodium-calcium exchanger, sarcoplasmic/endoplasmic reticulum calcium transporting ATPase 2, phospholamban, or cardiac calsequestrin. These data support local metabolic integration of vascular and myocyte function through adenosine signaling in the anemic fetal heart. PMID- 29791205 TI - Physiological hyperinsulinemia caused by acute hyperglycemia minimizes renal sodium loss by direct action on kidneys. AB - This study used acute, renal artery insulin infusion in conscious rats to test the hypothesis that hyperinsulinemia attenuates glucose-induced natriuresis by a direct renal mechanism. We reported previously that hyperinsulinemia was required to prevent ad libitum eating or an acute glucose bolus from causing excessive renal sodium loss. Rats were instrumented with renal artery, aortic, and femoral vein catheters and Data Sciences International blood pressure telemeters and were housed in metabolic cages. Insulin was clamped chronically at normal levels in two groups [vehicle infused (irV) and insulin infused (irI)] by administering streptozotocin and then infusing insulin intravenously 24 h/day to maintain normal blood glucose. Bolus glucose administration was used as a meal substitute to produce hyperglycemia that was not different between groups, and urinary sodium excretion (UNaV) was measured over the next 4 h. In the irV and control (C) rats, vehicle was infused in the renal artery during that period, whereas insulin was infused in the renal artery of the irI rats. Plasma insulin increased significantly in C rats but not in either of the clamped groups. UNaV in the irV rats, which could not increase circulating insulin levels, was approximately threefold greater than in C rats, similar to our previous report. However, allowing the kidney of irI rats to experience hyperinsulinemia via the renal artery insulin infusion completely prevented this, with no blood pressure differences. These data support our hypothesis that meal-induced increases in plasma insulin are a major component of normal sodium homeostasis, and that this occurs by direct action of insulin on the kidney. PMID- 29791206 TI - Effect of CT window settings on size measurements of the solid component in subsolid nodules: evaluation of prediction efficacy of the degree of pathological malignancy in lung adenocarcinoma. AB - OBJECTIVE: To investigate the predictive value of size measurements of the solid components in pulmonary subsolid nodules with different CT window settings and to evaluate the degree of pathological malignancy in lung adenocarcinoma. Methods: The preoperative chest CT images and pathological data of 125 patients were retrospectively evaluated. The analysis included 127 surgically resected lung adenocarcinomas that manifested as subsolid nodules. All subsolid nodules were divided into two groups: 69 in group A, including 22 adenocarcinomas in situ (AIS) and 47 minimally invasive adenocarcinomas (MIA); 58 in group B that included invasive pulmonary adenocarcinomas (IPA). The size of the solid component in the pulmonary subsolid nodules were calculated in one dimensional, two dimensional and three dimensional views using lung and mediastinal windows that were recorded as 1D-SCLW, 2D-SCLW, 3D-SCLW, 1D-SCMW, 2D-SCMW and 3D-SCMW, respectively. Furthermore, the volume of solid component with a threshold of 300HU was measured using lung window (3D-SCT). All the quantitative features were evaluated by the Mann-Whitney U test. Multivariate analysis was used to identify the significant predictor of the degree of pathological malignancy. Results: The 1D-SCLW, 2D-SCLW, 3D-SCLW, 1D-SCMW, 2D-SCMW, 3D-SCMW and 3D-SCT views of group B were significantly larger than those of group A (p < 0.001). The multivariate logistic regression analysis indicated that 3D-SCT (OR = 1.018, 95%CI: 1.005 ~ 1.03, p <0.05=was the independent predictive factor. The larger SCT was significantly associated with IPAs. Conclusion: 3D-SCT of subsolid nodules during preoperative CT can be used to predict the degree of pathological malignancy in lung adenocarcinoma, which may provide a more objective and convenient selection criterion for clinical application. Advances in knowledge: Applying threshold of -300 HU with lung window setting would be better than other window setting for the evaluation of solid component in subsolid nodules. Computer-aided volumetry of the solid component in subsolid nodules can more accurately predict the degree of pathological malignancy than the other dimensional measurements. PMID- 29791207 TI - Activation of TRPV4 stimulates transepithelial ion flux in a porcine choroid plexus cell line. AB - The choroid plexus (CP) epithelium plays a major role in the production of cerebrospinal fluid (CSF). A polarized cell line, the porcine CP-Riems (PCP-R) line, which exhibits many of the characteristics of the native epithelium, was used to study the effect of activation of the transient receptor potential vanilloid 4 (TRPV4) cation channel found in the PCP-R cells as well as in the native epithelium. Ussing-style electrophysiological experiments showed that activation of TRPV4 with a specific agonist, GSK1016790A, resulted in an immediate increase in both transepithelial ion flux and conductance. These changes were inhibited by either of two distinct antagonists, HC067047 or RN1734. The change in conductance was reversible and did not involve disruption of epithelial junctional complexes. Activation of TRPV4 results in Ca2+ influx, therefore, we examined whether the electrophysiological changes were the result of secondary activation of Ca2+-sensitive channels. PCP-R cells contain two Ca2+ activated K+ channels, the small conductance 2 (SK2) and the intermediate conductance (IK) channels. Based on inhibitor studies, the former is not involved in the TRPV4-mediated electrophysiological changes whereas one of the three isoforms of the IK channel (KCNN4c) may play a role in the apical secretion of K+. Blocking the activity of this IK isoform with TRAM34 inhibited the TRPV4 mediated change in net transepithelial ion flux and the increased conductance. These studies implicate TRPV4 as a hub protein in the control of CSF production through stimulation by multiple effectors resulting in transepithelial ion and subsequent water movement. PMID- 29791208 TI - Human soluble phospholipase A2 receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I. AB - Murine membrane-bound phospholipase A2 receptor 1 (PLA2R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2R. This study examined whether human soluble PLA2R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA2R (rsPLA2R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin beta1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2R suppressed integrin beta1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2R released from HEK293 cells transfected with a construct encoding human soluble PLA2R. rsPLA2R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2R with collagen-I. In addition, rsPLA2R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membrane-bound, full-length PLA2R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2R in human plasma. In conclusion, human recombinant soluble PLA2R inhibits integrin beta1 mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2R in human plasma has the same properties as rsPLA2R. PMID- 29791209 TI - Binding of intercellular adhesion molecule 1 to beta2-integrin regulates distinct cell adhesion processes on hepatic and cerebral endothelium. AB - Flowing polymorphonuclear neutrophils (PMNs) are forced to recruit toward inflamed tissue and adhere to vascular endothelial cells, which is primarily mediated by the binding of beta2-integrins to ICAM-1. This process is distinct among different organs such as liver and brain; however, the underlying kinetic and mechanical mechanisms regulating tissue-specific recruitment of PMNs remain unclear. Here, binding kinetics measurement showed that ICAM-1 on murine hepatic sinusoidal endothelial cells (LSECs) bound to lymphocyte function-associated antigen-1 (LFA-1) with higher on- and off-rates but lower effective affinity compared with macrophage-1 antigen (Mac-1), whereas ICAM-1 on cerebral endothelial cells (BMECs or bEnd.3 cells) bound to LFA-1 with higher on-rates, similar off-rates, and higher effective affinity compared with Mac-1. Physiologically, free crawling tests of PMN onto LSEC, BMEC, or bEnd.3 monolayers were consistent with those kinetics differences between two beta2-integrins interacting with hepatic sinusoid or cerebral endothelium. Numerical calculations and Monte Carlo simulations validated tissue-specific contributions of beta2 integrin-ICAM-1 kinetics to PMN crawling on hepatic sinusoid or cerebral endothelium. Thus, this work first quantified the biophysical regulation of PMN adhesion in hepatic sinusoids compared with cerebral endothelium. PMID- 29791211 TI - 'Knowing where I am': self-monitoring of blood glucose in diabetes. AB - Although the prevalence of all types of chronic conditions is increasing, diabetes is one of the few long-term metabolic disorders that individuals can successfully manage, monitor and control on a day-to-day basis. Self-monitoring of blood glucose (SMBG) is considered an essential component of diabetes self care management. When used appropriately, SMBG can help to identify factors associated with hyper- and hypoglycaemia, facilitate learning, and empower people with diabetes to make changes to improve their glycaemic control. SMBG can be a useful tool for healthcare providers, who can teach individuals to monitor glucose at specific times to assess the effectiveness of medications and guide medication management. However, there is an ongoing debate regarding whether, as is the case with type 1 diabetes, all people with type 2 diabetes should also be given the opportunity to learn about the value of, and skills required to, monitor blood glucose as appropriate to their specific needs. PMID- 29791212 TI - Indian novice nurses' perceptions of their role in caring for women who have experienced intimate partner violence. AB - BACKGROUND: intimate partner violence (IPV) is a significant health problem and a gross violation of the human rights of women. Nurses play an important role in providing support for these women. There is limited research on nurses' understanding and perceptions of their role in caring for women with IPV issues in India. AIM: to assess novice nurses' perceptions of self-efficacy, educational preparedness and their role in this area. METHODS: this was a cross-sectional descriptive survey carried out among a convenience sample of novice nurses (n=83) at a tertiary care centre using self-reported questionnaires. RESULTS: a majority of the subjects were confident and had adequate knowledge in dealing with women who have experienced IPV. A significantly positive relationship was found between educational preparedness and self-efficacy and attitudes towards nurses' roles in caring for these women. CONCLUSION: novice nurses were confident and held positive attitudes towards women who experienced IPV. Yet their self-efficacy in caring for these patients could be improved through continuing education and there is an urgent need to integrate comprehensive training on IPV to improve clinical competencies, including how to refer women for further support. PMID- 29791213 TI - Nurses' perspectives on pharmacology: why, what and at which point of the curricula should education be delivered? AB - AIMS AND OBJECTIVES: the study aimed to capture the views of nursing students and qualified nurses about pharmacology education and at which point the subject should be taught. BACKGROUND: drug errors are common in clinical practice. However, the presence of pharmacology education in nursing curricula varies, with few higher education institutes focusing on the topic in pre-registration years. DESIGN: a cross-sectional survey was carried out with 46 pre-registration, 18 post-qualification and 15 post-qualification nurse prescribing course students. RESULTS: most agreed that pharmacology education was crucial for practice. Post qualification participants ranked the topics of ethics and law as applied to pharmacology higher than pre-registration students. Qualified nurses ranked the topic of pharmacokinetics statistically higher than pre-registration students. Equal numbers of qualified participants favoured having pharmacology education as part of pre- and post-qualification programmes, either as a discrete module or incorporated in core modules. Pre-registration participants thought pharmacology education should be integrated throughout the programme. Most participants thought it should be taught face to face in the classroom. CONCLUSION: pharmacology education is valued by all nurses. Respondents mostly favoured a gradual integration of the subject in a programme of study, face to face. PMID- 29791214 TI - National Diabetes Inpatient Audit: how can inpatient teams make patients feel safer? PMID- 29791215 TI - Non-pharmacological approaches to non-cognitive symptoms in dementia. PMID- 29791216 TI - From staff nurse to nurse consultant: Continuing professional development part 2: What opportunities do you have? AB - John Fowler, Educational Consultant, explores continued professional development for the clinically based nurse, looking at making the most of opportunities. PMID- 29791217 TI - Prevention of dehydration in hospital patients. AB - Dehydration is widely linked to increased risk of mortality in patients who are acutely unwell, and it also increases the risk of further illness. Despite being recognised nationwide as a cause for concern, 45% of hospital patients will become dehydrated upon admission, suggesting that more needs to be done to prevent dehydration. The use of bedside water devices allows patients to drink freely without assistance. Access to these can reduce a patient's length of stay in hospital and minimise the risk of developing a urinary tract infection. However, further research is needed to fully assess the impact of having such devices at the bedside. PMID- 29791218 TI - Menace of predatory journals. PMID- 29791219 TI - Approaches to leadership and managing change in the NHS. AB - The NHS is continually changing as research evidence leads to new practices and technology transforms the workplace. Resistance to some changes may occur because of staff fears about adapting to and coping with new methods. This is where change models and leadership are important. This article discusses changes taking place in the NHS, and some theoretical models of change. Leadership styles are also discussed, including those most useful for the nurse to use when leading a team and implementing change. PMID- 29791220 TI - Independent acute hospitals must act to improve patient safety. AB - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent University, discusses a Care Quality Commission (CQC) report on independent acute hospitals. PMID- 29791221 TI - An insight into living with diabetes. AB - Laura Lennard, Children's Diabetes Nurse, West Hertfordshire Hospitals NHS Trust, reflects on the challenges of encouraging behaviour change and the importance of understanding patients' real-life experiences. PMID- 29791222 TI - Celebrating contemporary nursing practice. PMID- 29791223 TI - Flexible working in the NHS. AB - Sam Foster, Chief Nurse, Oxford University Hospitals, questions whether NHS policies around flexible working are fit for purpose. PMID- 29791224 TI - Developing standards of care for children with ongoing health needs. AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses a recently published report from a consortium of health agencies led by the Royal College of Paediatrics and Child Health. PMID- 29791225 TI - My first experiences of nurse leadership. AB - Alan Nobbs reflects on his early experiences of nurse leadership, most of which have thankfully not stood the test of time. PMID- 29791226 TI - CNO summit: professional collaboration and patient involvement are key. AB - Ian Peate, Editor-in-Chief, British Journal of Nursing, reports on the issues highlighted at the recent meeting of nursing and midwifery leaders, including nurse-patient ratios, resilient leadership and integrated care. PMID- 29791228 TI - Considering the numbers. PMID- 29791227 TI - Jordanian oncology nurses' knowledge of managing chemotherapy-induced nausea and vomiting. AB - BACKGROUND: health practitioners, especially oncology nurses, play an important role in assessing and managing chemotherapy-induced nausea and vomiting (CINV). Oncology nurses need adequate knowledge and skills to optimally assess and manage CINV in oncology settings. AIM: the study intended to assess Jordanian oncology nurses' knowledge of assessing and managing CINV. METHODS: a cross-sectional design was used to survey 229 oncology nurses working in oncology units in three hospitals. FINDINGS: most participants were female (62.9%). The age rage was 21 55 years, with a mean age of 29.9 years (SD=6.2). The mean overall knowledge score was low at 4.7 (SD=3.5) (95% CI=4.40-5.01). Poor knowledge of CINV assessment and management were noted. CONCLUSION: oncology nurses' knowledge about the assessment and management of CINV is inadequate, and improvements in knowledge are needed. An educational intervention is recommended, which needs to be tested to ensure that it is both effective and feasible to provide. PMID- 29791229 TI - Can we give culturally competent care? AB - Sophie Kelly, currently studying for MA Nursing (children and young people), University of Salford, reflects on the challenges of providing care for families with differing cultural backgrounds. PMID- 29791230 TI - Assessing anxiety and depression in cancer patients. AB - BACKGROUND: empirical evidence suggests that anxiety and depression in cancer patients is underdiagnosed and subsequently this patient population receives little or no support or intervention to address their psychosocial needs. It is often difficult to distinguish between normal emotional distress experienced following a cancer diagnosis and anxiety and depression, which can have a significant impact on coping mechanisms and subsequent outcomes. AIM: a qualitative study using the Hospital Anxiety and Depression Scale (HADS) was undertaken in the National Centre for Cancer Care and Research in Qatar. The driver for change was to provide evidence of the need for an assessment to be incorporated into the nursing admission process as a means of early detection and onward referral for more formal interventions if required. The sample size was 57. FINDINGS: the evidence from the outcome data supported the hypothesis that anxiety and depression were present in a significant number of the sample group. This would support the proposal of early screening and onward referral. A number of patients surveyed expressed moderate to severe depression, which may impact negatively on outcomes. CONCLUSION: screening for anxiety and depression in adult cancer patients should form part of an early nursing assessment to identify those who may benefit from more structured interventions. HADS is a useful screening tool; however, further research is required on validating tools used to screen for anxiety and depression in cancer and chronic disease in different cultures to ensure validity and reliability of outcome data. PMID- 29791231 TI - The Future Is Today. PMID- 29791232 TI - The Role of Interleukin-31 Polymorphisms in Non-Small Cell Lung Cancer Genetic Susceptibility and Clinical Outcome. AB - BACKGROUND: Interleukin-31 (IL-31), a novel T helper type 2 effector cytokine, is known to have an important effect on the pathogenesis of allergic disease and tumors. However, the impact of IL-31 on human lung cancer remains unclear. METHODS: This study explored the role of IL-31 polymorphisms in lung cancer and sought to characterize how IL-31 polymorphisms correlate with lung cancer tumorigenesis and patient survival rates. Using a single-nucleotide polymorphism genotype assay, we examined the expression of two IL-31 polymorphisms (rs7977932 and rs4758680) in samples from 302 lung cancer patients and 493 control cases. RESULTS: Lung cancer patients who were homozygous CC for rs7977932 or carried the G allele of rs4758680 had significantly poorer prognoses compared to those who did not have these genotypes. Moreover, the rs7977932 CC genotype was significantly associated with metastasis and poor survival status in lung adenocarcinoma. CONCLUSION: Our study indicates the importance of IL-31 polymorphisms for susceptibility and survival status in lung cancer. PMID- 29791233 TI - Association of a Chromosome Locus 9p21.3 CDKN2B-AS1 Variant rs4977574 with Hypertension: The TAMRISK Study. AB - AIMS: Chromosome locus 9p21.3 CDKN2B antisense RNA 1 (CDKN2B-AS1) has been found to contain multiple genetic markers for coronary artery disease (CAD) by genome wide association studies (GWAS). Of these, the association of variants rs4977574, rs10757274, and rs2383206 with hypertension was studied in the Tampere adult population cardiovascular risk study (TAMRISK). MATERIALS AND METHODS: A Finnish cohort of 336 subjects diagnosed with hypertension and 444 controls was analyzed. Samples were genotyped for the CDKN2B-AS1 polymorphisms using Kompetitive Allele Specific PCR (KASP) or TaqMan techniques. RESULTS: Individuals with the minor genotype GG of rs4977574 had less hypertension compared to the other genotypes (p = 0.048, OR 1.58, 95% CI 1.01-2.48). The variants rs2383206 and rs10757274 were not associated with hypertension. CONCLUSIONS: Our findings suggest that the GG genotype of the CDKN2B-AS1 gene variant rs4977574, which has been previously associated with an increased CAD risk, is also associated with a decreased susceptibility to the development of hypertension. PMID- 29791234 TI - Searching for the Great Oxidation Event in North America: A Reappraisal of the Huronian Supergroup by SIMS Sulfur Four-Isotope Analysis. AB - Sedimentological observations from the Paleoproterozoic Huronian Supergroup are suggested to mark the rise in atmospheric oxygen at that time, which is commonly known as the Great Oxidation Event (GOE) and typically coupled with a transition from mass-independent fractionation (MIF) to mass-dependent fractionation (MDF) of sulfur isotopes. An early in situ study of S three-isotopes across the Huronian Supergroup by Papineau et al. ( 2007 ) identified a weak MIF-MDF transition. However, the interpretation and stratigraphic placement of this transition is ambiguous. In this study, all four S isotopes were analyzed for the first time in two Huronian drill cores by secondary ion mass spectrometer (SIMS), and both Delta33S and Delta36S were calculated. Based on improved precision and detailed petrography, we reinterpret the dominance of pyrrhotite in the studied sections, which was previously proposed as "early authigenic" in origin, as resulting from regional metamorphism. Small but analytically resolvable nonzero values of Delta33S (from -0.070/00 to +0.380/00) and Delta36S (from -4.10/00 to +1.00/00) persist throughout the lower Huronian Supergroup. Neither pronounced MIF-S signals nor a MIF-MDF transition are seen in this study. Four scenarios are proposed for the genesis of small nonzero Delta33S and Delta36S values in the Huronian: homogenization by regional metamorphism, recycling from older pyrite, dilution by magmatic fluids, and the occurrence of MDF. We argue that the precise location of the MIF-MDF transition in the Huronian remains unsolved. This putative transition may have been erased by postdepositional processes in the lower Huronian Supergroup, or may be located in the upper Huronian Supergroup. Our study highlights the importance of integrated scanning electron microscopy and secondary ion mass spectrometry techniques in deep-time studies and suggests that different analytical methods (bulk vs. SIMS) and diagenetic history (primary vs. metamorphic) among different basins may have caused inconsistent interpretations of S isotope profiles of the GOE successions at a global scale. Key Words: Great Oxidation Event (GOE)-Secondary ion mass spectrometer (SIMS) Paleoproterozoic-Sulfur isotopes-Mass independent fractionation (MIF). Astrobiology 18, 519-538. PMID- 29791235 TI - Long-Term Planetary Habitability and the Carbonate-Silicate Cycle. AB - The potential habitability of an exoplanet is traditionally assessed by determining whether its orbit falls within the circumstellar "habitable zone" of its star, defined as the distance at which water could be liquid on the surface of a planet (Kopparapu et al., 2013 ). Traditionally, these limits are determined by radiative-convective climate models, which are used to predict surface temperatures at user-specified levels of greenhouse gases. This approach ignores the vital question of the (bio)geochemical plausibility of the proposed chemical abundances. Carbon dioxide is the most important greenhouse gas in Earth's atmosphere in terms of regulating planetary temperature, with the long-term concentration controlled by the balance between volcanic outgassing and the sequestration of CO2 via chemical weathering and sedimentation, as modulated by ocean chemistry, circulation, and biological (microbial) productivity. We developed a model that incorporates key aspects of Earth's short- and long-term biogeochemical carbon cycle to explore the potential changes in the CO2 greenhouse due to variance in planet size and stellar insolation. We find that proposed changes in global topography, tectonics, and the hydrological cycle on larger planets result in proportionally greater surface temperatures for a given incident flux. For planets between 0.5 and 2 R?, the effect of these changes results in average global surface temperature deviations of up to 20 K, which suggests that these relationships must be considered in future studies of planetary habitability. Key Words: Planets-Atmospheres-Carbon dioxide Biogeochemistry. Astrobiology 18, 469-480. PMID- 29791236 TI - The Anthropocene Generalized: Evolution of Exo-Civilizations and Their Planetary Feedback. AB - We present a framework for studying generic behaviors possible in the interaction between a resource-harvesting technological civilization (an exo-civilization) and the planetary environment in which it evolves. Using methods from dynamical systems theory, we introduce and analyze a suite of simple equations modeling a population which consumes resources for the purpose of running a technological civilization and the feedback those resources drive on the state of the host planet. The feedbacks can drive the planet away from the initial state the civilization originated in and into domains that are detrimental to its sustainability. Our models conceptualize the problem primarily in terms of feedbacks from the resource use onto the coupled planetary systems. In addition, we also model the population growth advantages gained via the harvesting of these resources. We present three models of increasing complexity: (1) Civilization planetary interaction with a single resource; (2) Civilization-planetary interaction with two resources each of which has a different level of planetary system feedback; (3) Civilization-planetary interaction with two resources and nonlinear planetary feedback (i.e., runaways). All three models show distinct classes of exo-civilization trajectories. We find smooth entries into long-term, "sustainable" steady states. We also find population booms followed by various levels of "die-off." Finally, we also observe rapid "collapse" trajectories for which the population approaches n = 0. Our results are part of a program for developing an "Astrobiology of the Anthropocene" in which questions of sustainability, centered on the coupled Earth-system, can be seen in their proper astronomical/planetary context. We conclude by discussing the implications of our results for both the coupled Earth system and for the consideration of exo civilizations across cosmic history. Key Words: Anthropocene-Astrobiology Civilization-Dynamical system theory-Exoplanets-Population dynamics. Astrobiology 18, 503-518. PMID- 29791237 TI - The future of chronic lymphocytic leukemia: potential directions from ASH 2017. AB - INTRODUCTION: Novel targeted therapies - including ibrutinib, venetoclax, and idelalisib - have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). Therefore, studying combinations of novel agents (NAs) with a distinct mechanism of action and nonoverlapping toxicities is challenging. Area covered: The 2017 American Society Hematology Annual Meeting has represented a showcase for several trials combining NAs. These studies are currently evaluating the efficacy NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody), and NA plus chemo-immunotherapy. Expert commentary: The development of well-tolerated, highly effective combination strategies with curative potential for patients with CLL is becoming a realistic goal in CLL. From a practical standpoint, it is hard to determine which regimen will be most beneficial. Until studies of association will provide more mature results, the sequencing of NA remains a reasonable approach. PMID- 29791238 TI - Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series. AB - The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 ug/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects. PMID- 29791243 TI - AMCP Partnership Forum: Managing Care in the Wave of Precision Medicine. AB - Precision medicine, the customization of health care to an individual's genetic profile while accounting for biomarkers and lifestyle, has increasingly been adopted by health care stakeholders to guide the development of treatment options, improve treatment decision making, provide more patient-centered care, and better inform coverage and reimbursement decisions. Despite these benefits, key challenges prevent its broader use and adoption. On December 7-8, 2017, the Academy of Managed Care Pharmacy convened a group of stakeholders to discuss these challenges and provide recommendations to facilitate broader adoption and use of precision medicine across health care settings. These stakeholders represented the pharmaceutical industry, clinicians, patient advocacy, private payers, device manufacturers, health analytics, information technology, academia, and government agencies. Throughout the 2-day forum, participants discussed evidence requirements for precision medicine, including consistent ways to measure the utility and validity of precision medicine tests and therapies, limitations of traditional clinical trial designs, and limitations of value assessment framework methods. They also highlighted the challenges with evidence collection and data silos in precision medicine. Interoperability within and across health systems is hindering clinical advancements. Current medical coding systems also cannot account for the heterogeneity of many diseases, preventing health systems from having a complete understanding of their patient population to inform resource allocation. Challenges faced by payers, such as evidence limitations, to inform coverage and reimbursement decisions in precision medicine, as well as legal and regulatory barriers that inhibit more widespread data sharing, were also identified. While a broad range of perspectives was shared throughout the forum, participants reached consensus across 2 overarching areas. First, there is a greater need for common definitions, thresholds, and standards to guide evidence generation in precision medicine. Second, current information silos are preventing the sharing of valuable data. Collaboration among stakeholders is needed to support better information sharing, awareness, and education of precision medicine for patients. The recommendations brought forward by this diverse group of experts provide a set of solutions to spur widespread use and application of precision medicine. Taken together, successful adoption and use of precision medicine will require input and collaboration from all sectors of health care, especially patients. DISCLOSURES This AMCP Partnership Forum and the development of the proceedings document were supported by Amgen, Foundation Medicine, Genentech, Gilead, MedImpact, National Pharmaceutical Council, Precision for Value, Sanofi, Takeda, and Xcenda. PMID- 29791242 TI - Liver-targeted delivery of insulin-loaded nanoparticles via enterohepatic circulation of bile acids. AB - Liver is the primary acting site of insulin. In this study, we developed innovative nanoparticles for oral and liver-targeted delivery of insulin by using enterohepatic circulation of bile acids. The nanoparticles were produced from cholic acid and quaternary ammonium modified chitosan derivative and hydroxypropyl methylcellulose phthalate (HPMCP). The nanoparticles had a diameter of 239 nm, an insulin loading efficiency of 90.9%, and a loading capacity of 18.2%. Cell culture studies revealed that the cholic acid groups effectively enhanced the transport of the nanoparticles through Caco-2 cell monolayer and greatly increased the absorption of the nanoparticles in HepG-2 cells via bile acid transporter mechanism. Ex vivo fluorescence images of ileum section, gastrointestinal tract, and liver demonstrated that the HPMCP increased the mucoadhesion of the nanoparticles in ileum, and the cholic acid groups facilitated the absorptions of the nanoparticles in both ileum and liver by use of bile acid transporters via enterohepatic circulation of bile acids. The therapy for diabetic mice displayed that the oral nanoparticle group could maintain hypoglycemic effect for more than 24 h and its pharmacological availability was about 30% compared with the insulin injection group. For the first time, this study demonstrates that using enterohepatic circulation of bile acids is an effective strategy for oral delivery of insulin. PMID- 29791241 TI - Neutrophil-mediated delivery of pixantrone-loaded liposomes decorated with poly(sialic acid)-octadecylamine conjugate for lung cancer treatment. AB - Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)-octadecylamine conjugate (PSA-ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity. Simultaneously, in vitro and in vivo cellular uptake studies confirmed that PSA-decorated liposomes provided an enhanced accumulation of liposomes in PBNs. An in vivo study presented that the anti-tumor activity of Pix PSL was superior to that of other Pix formulations, probably due to the efficient targeting of PBNs by Pix-PSL, after which PBN containing Pix-PSL (Pix-PSL/PBNs) in the blood circulation are recruited by the tumor microenvironment. These findings suggest that PSA-decorated liposomal Pix may provide a neutrophil mediated drug delivery system (DDS) for the eradication of tumors, which represents a promising approach for the tumor targeting of chemotherapeutic treatments. PMID- 29791244 TI - The need for mapping personal goals to exercise dosage in community-based exercise programs for people with Parkinson's disease. AB - PURPOSE: Community-based exercise can support long-term management of Parkinson's disease, although it is not known if personal goals are met in these programs. The objectives of this study were to: (1) examine the goals of community based exercise programs from the participant and instructor perspectives; (2) establish the extent to which these programs meet self-described exercise outcomes; and (3) explore participant and instructor perspectives on barriers to meeting exercise expectations. MATERIALS AND METHODS: This study explores the experiences of people with Parkinson's disease participating in a structured exercise program at six community sites. A mixed-methods approach was used, including participant and instructor interviews, assessment of exercise intensity, and mapping of exercise dosage to participant goals. Twenty-four exercise participants provided interview, quality of life, and exercise intensity data. RESULTS: Twenty-one participants exercised for primary management of their Parkinson's disease. None met the exercise dosage necessary to meet this primary objective, although 60% met exercise dosage required to prevent disuse deconditioning. Participants and instructors did not describe similar goals for the community-based exercise program. CONCLUSIONS: Community-based exercise programs could be optimized by better aligning participant goals and exercise intensity. PMID- 29791245 TI - PI(3,5)P2 controls vacuole potassium transport to support cellular osmoregulation. AB - Lysosomes are dynamic organelles with critical roles in cellular physiology. The lysosomal signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a key regulator that has been implicated to control lysosome ion homeostasis, but the scope of ion transporters targeted by PI(3,5)P2 and the purpose of this regulation is not well understood. Through an unbiased screen in Saccharomyces cerevisiae, we identified loss-of-function mutations in the vacuolar H+-ATPase (V ATPase) and in Vnx1, a vacuolar monovalent cation/proton antiporter, as suppressor mutations that relieve the growth defects and osmotic swelling of vacuoles (lysosomes) in yeast lacking PI(3,5)P2. We observed that depletion of PI(3,5)P2 synthesis in yeast causes a robust accumulation of multiple cations, most notably an ~85 mM increase in the cellular concentration of potassium, a critical ion used by cells to regulate osmolarity. The accumulation of potassium and other cations in PI(3,5)P2-deficient yeast is relieved by mutations that inactivate Vnx1 or inactivate the V-ATPase and by mutations that increase the activity of a vacuolar cation export channel, Yvc1. Collectively, our data demonstrate that PI(3,5)P2 signaling orchestrates vacuole/lysosome cation transport to aid cellular osmoregulation. PMID- 29791246 TI - Curative Stereotactic Ablative Radiotherapy for a Locally Advanced Basal Cell Carcinoma in an Elderly Patient. PMID- 29791248 TI - ddY Mice Fed 10% Fat Diet Exhibit High p27KIP Expression and Delayed Hepatocyte DNA Synthesis During Liver Regeneration. AB - BACKGROUND: Excessive intake of a high-calorie diet has been implicated in the development of non-alcoholic fatty liver disease (NAFLD). Several studies have investigated the effect of NAFLD on liver regeneration, but the effects of simple steatosis have been found to be inconsistent. We aimed to assess whether the initial phase of diet-induced lipid accumulation, induced by a diet containing moderate levels of fat, impairs liver regeneration after partial hepatectomy (PHx) of mice. METHODS: Male ddY mice are prone to obesity, even when fed a relatively low-fat diet (FD). A model of early simple steatosis was created by feeding a 10% FD for 6 weeks to male ddY mice. Liver regeneration rate, DNA synthesis in hepatocytes, and DNA damage were then assessed. RESULTS: FD-fed mice had a slightly higher body mass (44.5 +/- 2.6 grams vs. 48.1 +/- 3.6 grams, P < 0.05), but not liver mass (2.55 +/- 0.37 grams vs. 2.69 +/- 0.26 grams). Lipid droplets appeared in FD-fed mouse hepatocytes and Oil Red O staining was five times as intense as in control mice. In FD-fed mice, liver regeneration rate after two-thirds PHx was lower and impaired DNA replication was also observed. FD induced the expression of the cyclin-dependent kinase inhibitor p27KIP, but not p21CIP. Moreover, greater histone 2A.X phosphorylation was observed, indicating that FD caused DNA damage. CONCLUSIONS: Even short-term feeding of a moderately high FD to male ddY mice results in lipid accumulation in hepatocytes, DNA damage, and greater expression of p27KIP, implying lower DNA synthesis. PMID- 29791247 TI - A Randomized Trial of a Family-Support Intervention in Intensive Care Units. AB - BACKGROUND: Surrogate decision makers for incapacitated, critically ill patients often struggle with decisions related to goals of care. Such decisions cause psychological distress in surrogates and may lead to treatment that does not align with patients' preferences. METHODS: We conducted a stepped-wedge, cluster randomized trial involving patients with a high risk of death and their surrogates in five intensive care units (ICUs) to compare a multicomponent family support intervention delivered by the interprofessional ICU team with usual care. The primary outcome was the surrogates' mean score on the Hospital Anxiety and Depression Scale (HADS) at 6 months (scores range from 0 to 42, with higher scores indicating worse symptoms). Prespecified secondary outcomes were the surrogates' mean scores on the Impact of Event Scale (IES; scores range from 0 to 88, with higher scores indicating worse symptoms), the Quality of Communication (QOC) scale (scores range from 0 to 100, with higher scores indicating better clinician-family communication), and a modified Patient Perception of Patient Centeredness (PPPC) scale (scores range from 1 to 4, with lower scores indicating more patient- and family-centered care), as well as the mean length of ICU stay. RESULTS: A total of 1420 patients were enrolled in the trial. There was no significant difference between the intervention group and the control group in the surrogates' mean HADS score at 6 months (11.7 and 12.0, respectively; beta coefficient, -0.34; 95% confidence interval [CI], -1.67 to 0.99; P=0.61) or mean IES score (21.2 and 20.3; beta coefficient, 0.90; 95% CI, -1.66 to 3.47; P=0.49). The surrogates' mean QOC score was better in the intervention group than in the control group (69.1 vs. 62.7; beta coefficient, 6.39; 95% CI, 2.57 to 10.20; P=0.001), as was the mean modified PPPC score (1.7 vs. 1.8; beta coefficient, 0.15; 95% CI, -0.26 to -0.04; P=0.006). The mean length of stay in the ICU was shorter in the intervention group than in the control group (6.7 days vs. 7.4 days; incidence rate ratio, 0.90; 95% CI, 0.81 to 1.00; P=0.045), a finding mediated by the shortened mean length of stay in the ICU among patients who died (4.4 days vs. 6.8 days; incidence rate ratio, 0.64; 95% CI, 0.52 to 0.78; P<0.001). CONCLUSIONS: Among critically ill patients and their surrogates, a family-support intervention delivered by the interprofessional ICU team did not significantly affect the surrogates' burden of psychological symptoms, but the surrogates' ratings of the quality of communication and the patient- and family centeredness of care were better and the length of stay in the ICU was shorter with the intervention than with usual care. (Funded by the UPMC Health System and the Greenwall Foundation; PARTNER ClinicalTrials.gov number, NCT01844492 .). PMID- 29791249 TI - Keeping Your Cool - Doing Ebola Research during an Emergency. PMID- 29791250 TI - Interview: The New Silk Road-Health as Soft Power. PMID- 29791251 TI - Prevalence of CTX-M-Type Extended-Spectrum beta-Lactamase-Producing Escherichia coli B2-O25-ST131 H30R Among Residents in Nonacute Care Facilities in Japan. AB - We investigated the prevalence and characteristics of extended-spectrum beta lactamase (ESBL)-producing Escherichia coli among 258 residents of long-term care facilities (LTCFs) in Japan. Out of 258 fecal samples collected from nine LTCFs between November 2015 and March 2017, we recovered 59 ESBL-producing E. coli isolates. All isolates carried blaCTX-M genes, mainly blaCTX-M-27 (42.4%), blaCTX M-14 (23.7%), and blaCTX-M-15 (18.6%). The isolates showed 7 serotypes (STs), including ST131 (n = 49, 83.1%) and ST38 (n = 4, 6.8%), and 47 (79.7%) out of 49 isolates belonging to ST131 were identified as H30R. The 59 ESBL producers were divided into four groups, B2 (86.4%), D (8.5%), A (3.4%), and C (1.7%); 44 (74.6%) were epidemic clone B2-O25-ST131 H30R, of which 21, 11, and 6 harbored blaCTX-M-27, blaCTX-M-15, and blaCTX-M-14, respectively. Most plasmids were of IncF replicon types (n = 33), and 22 blaCTX-M-27-carrying plasmids showed multiple replicon types, including IncFII, FIA, and FIB. The ESBL producers were susceptible to imipenem, amikacin, and fosfomycin, but resistant to ceftazidime (49.2%), and ciprofloxacin (88.1%); in particular, the isolates harboring the blaCTX-M-15 gene showed significantly high resistance rate to ceftazidime (p < 0.01). Our findings indicate that a considerable proportion of the examined LTCF residents carried ESBL-producing E. coli isolates in feces and had high prevalence of epidemic clone B2-O25-ST131. Furthermore, continuous investigations would be very necessary to monitor actual carriage states of ESBL-producers among the LTCF residents from the viewpoint of both public health and healthcare viewpoints. PMID- 29791252 TI - Immediate effects of a distal gait modification during stair descent in individuals with patellofemoral pain. AB - BACKGROUND: Knee pain during stair managing is a common complaint among individuals with PFP and can negatively affect their activities of daily living. Gait modification programs can be used to decrease patellofemoral pain. Immediate effects of a stair descent distal gait modification session that intended to emphasize forefoot landing during stair descent are described in this study. OBJECTIVES: To analyze the immediate effects of a distal gait modification session on lower extremity movements and intensity of pain in women with patellofemoral pain during stair descent. METHOD: Nonrandomized controlled trial. Sixteen women with patellofemoral pain were allocated into two groups: (1) Gait Modification Group (n = 8); and 2) Control Group (n = 8). The intensity of pain (visual analog scale) and kinematics of knee, ankle, and forefoot (multi segmental foot model) during stair descent were assessed before and after the intervention. RESULTS: After the gait modification session, there was an increase of forefoot eversion and ankle plantarflexion as well as a decrease of knee flexion. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. CONCLUSION: The distal gait modification session changed the lower extremity kinetic chain strategy of movement, increasing foot and ankle movement contribution and decreasing knee contribution to the task. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. To emphasize forefoot landing may be a useful intervention to immediately relieve pain in patients with patellofemoral pain during stair descent. Clinical studies are needed to verify the gait modification session effects in medium and long terms. PMID- 29791253 TI - Nurse-Led Communication in the Intensive Care Unit. PMID- 29791255 TI - The Calorie-Labeling Saga - Federal Preemption and Delayed Implementation of Public Health Law. PMID- 29791256 TI - NLRP6 Induces Pyroptosis by Activation of Caspase-1 in Gingival Fibroblasts. AB - NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, has been reported to participate in inflammasome formation. Activation of inflammasome triggers a caspase-1-dependent programming cell death called pyroptosis. However, whether NLRP6 induces pyroptosis has not been investigated. In this study, we showed that NLRP6 overexpression activated caspase-1 and gasdermin-D and then induced pyroptosis of human gingival fibroblasts, resulting in release of proinflammatory mediators interleukin (IL)-1beta and IL-18. Moreover, NLRP6 was highly expressed in gingival tissue of periodontitis compared with healthy controls. Porphyromonas gingivalis, which is a commensal bacterium and has periodontopathic potential, induced pyroptosis of gingival fibroblasts by activation of NLRP6. Together, we, for the first time, identified that NLRP6 could induce pyroptosis of gingival fibroblasts by activation of caspase-1 and may play a role in periodontitis. PMID- 29791254 TI - A genome-wide microRNA screen identifies regulators of tetraploid cell proliferation. AB - Tetraploid cells, which are most commonly generated by errors in cell division, are genomically unstable and have been shown to promote tumorigenesis. Recent genomic studies have estimated that ~40% of all solid tumors have undergone a genome-doubling event during their evolution, suggesting a significant role for tetraploidy in driving the development of human cancers. To safeguard against the deleterious effects of tetraploidy, nontransformed cells that fail mitosis and become tetraploid activate both the Hippo and p53 tumor suppressor pathways to restrain further proliferation. Tetraploid cells must therefore overcome these antiproliferative barriers to ultimately drive tumor development. However, the genetic routes through which spontaneously arising tetraploid cells adapt to regain proliferative capacity remain poorly characterized. Here, we conducted a comprehensive gain-of-function genome-wide screen to identify microRNAs (miRNAs) that are sufficient to promote the proliferation of tetraploid cells. Our screen identified 23 miRNAs whose overexpression significantly promotes tetraploid proliferation. The vast majority of these miRNAs facilitate tetraploid growth by enhancing mitogenic signaling pathways (e.g., miR-191-3p); however, we also identified several miRNAs that impair the p53/p21 pathway (e.g., miR-523-3p), and a single miRNA (miR-24-3p) that potently inactivates the Hippo pathway via down regulation of the tumor suppressor gene NF2. Collectively, our data reveal several avenues through which tetraploid cells may regain the proliferative capacity necessary to drive tumorigenesis. PMID- 29791257 TI - The use of direct oral anticoagulants in the treatment of acute venous thromboembolism in cancer patients. AB - INTRODUCTION: After the CLOT study, LMWHs (low-molecular weight heparins) have gradually replaced warfarin as the treatment of choice for VTE (venous thromboembolism) in cancer patients. Randomized controlled studies comparing DOACs (direct oral anticoagulants) to LMWHs in cancer patients are still limited. However, new emerging data are supporting the use of DOACs in cancer-associated thrombosis. Areas covered: This review will discuss the recent studies that addressed the utilization of such agents in the treatment of VTE in cancer patients. It will also address challenges that can be encountered while using these agents particularly in cancer patients. Expert commentary: Up until the Hokusai VTE Cancer study, data on the use of DOACs in cancer patients have been limited but supportive of their use in such patients. The Hokusai VTE Cancer study shows that edoxaban is non-inferior to dalteparin in prevention of recurrent VTE but at expense of higher major bleeding namely in patients with gastrointestinal cancer. Although further studies involving other DOACs may reinforce the efficacy of DOACs in this population of patients, studies looking at subpopulation of cancer patients may be of more clinical value to clinicians who are trying to balance between treatment of thrombosis and risks of bleeding. PMID- 29791260 TI - Assessment of the Power Required for Optimal Use of Current Inhalation Devices. AB - BACKGROUND: Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a clear overview on performance requirements of standard inhalation devices that should be met by the patient's breathing power and to develop a new method to measure the individual performance data. MATERIALS AND METHODS: An optimum and still acceptable required breathing power (P in watts) was calculated for each device with the aid of individual device flow rates (determined by a literature search) and the flow resistances (by measuring the pressure drop over the different inhalation devices). For the in vivo part of the study, peak inspiratory flow and peak inspiratory pressure drop were measured in 21 adult patients with asthma or chronic obstructive pulmonary disease and healthy volunteers and the peak inspiratory power (PIPO in watts) was calculated. RESULTS: Nearly no power is needed to achieve optimum results when using pressurized metered dose inhalers. For dry powder inhalers, the required power depends on the specific inhalation device. CONCLUSIONS: Inhalation devices impose differing demands on the inspiratory breathing power of patients. To ensure adequate use of the different devices, a cheap and simple assessment of patients' PIPO may be one option. PMID- 29791259 TI - A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation. AB - BACKGROUND: Whether financial incentives, pharmacologic therapies, and electronic cigarettes (e-cigarettes) promote smoking cessation among unselected smokers is unknown. METHODS: We randomly assigned smokers employed by 54 companies to one of four smoking-cessation interventions or to usual care. Usual care consisted of access to information regarding the benefits of smoking cessation and to a motivational text-messaging service. The four interventions consisted of usual care plus one of the following: free cessation aids (nicotine-replacement therapy or pharmacotherapy, with e-cigarettes if standard therapies failed); free e cigarettes, without a requirement that standard therapies had been tried; free cessation aids plus $600 in rewards for sustained abstinence; or free cessation aids plus $600 in redeemable funds, deposited in a separate account for each participant, with money removed from the account if cessation milestones were not met. The primary outcome was sustained smoking abstinence for 6 months after the target quit date. RESULTS: Among 6131 smokers who were invited to enroll, 125 opted out and 6006 underwent randomization. Sustained abstinence rates through 6 months were 0.1% in the usual-care group, 0.5% in the free cessation aids group, 1.0% in the free e-cigarettes group, 2.0% in the rewards group, and 2.9% in the redeemable deposit group. With respect to sustained abstinence rates, redeemable deposits and rewards were superior to free cessation aids (P<0.001 and P=0.006, respectively, with significance levels adjusted for multiple comparisons). Redeemable deposits were superior to free e-cigarettes (P=0.008). Free e cigarettes were not superior to usual care (P=0.20) or to free cessation aids (P=0.43). Among the 1191 employees (19.8%) who actively participated in the trial (the "engaged" cohort), sustained abstinence rates were four to six times as high as those among participants who did not actively engage in the trial, with similar relative effectiveness. CONCLUSIONS: In this pragmatic trial of smoking cessation, financial incentives added to free cessation aids resulted in a higher rate of sustained smoking abstinence than free cessation aids alone. Among smokers who received usual care (information and motivational text messages), the addition of free cessation aids or e-cigarettes did not provide a benefit. (Funded by the Vitality Institute; ClinicalTrials.gov number, NCT02328794 .). PMID- 29791258 TI - Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide induced hepatotoxicity via up-regulation of the Nrf2 pathway. AB - Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18alpha glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated in vitro and in vivo, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including UGT1A, BSEP, and MRP2, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG. PMID- 29791261 TI - A systematic review of grounded theory studies in physiotherapy. AB - AIM: This systematic review aimed at appraising the methodological rigor of grounded theory research published in the field of physiotherapy to assess how the methodology is understood and applied. A secondary aim was to provide research implications drawn from the findings to guide future grounded theory methodology (GTM) research. METHODS: A systematic search was conducted in MEDLINE, CINHAL, SPORT Discus, Science Direct, PubMed, Scopus, and Web of Science to identify studies in the field of physiotherapy that reported using GTM and/or methods in the study title and/or abstract. The descriptive characteristics and methodological quality of eligible studies were examined using grounded theory methodology assessment guidelines. FINDINGS: The review included 68 studies conducted between 1998 and 2017. The findings showed that GTM is becoming increasingly used by physiotherapy researchers. Thirty-six studies (53%) demonstrated a good understanding and appropriate application of GTM. Thirty-two studies (47%) presented descriptive findings and were considered to be of poor methodological quality. CONCLUSIONS: There are several key tenets of GTM that are integral to the iterative process of qualitative theorizing and need to be applied throughout all research practices including sampling, data collection, and analysis. PMID- 29791262 TI - Flow Recirculation in Cartilaginous Ring Cavities of Human Trachea Model. AB - BACKGROUND: Despite the prevailing assumption of "smooth trachea walls" in respiratory fluid dynamics research, recent investigations have demonstrated that cartilaginous rings in the trachea and main bronchi have a significant effect on the flow behavior and in particle deposition. However, there is not enough detailed information about the underlying physics of the interaction between the cartilage rings and the flow. MATERIALS AND METHODS: This study presents an experimental observation of a simplified Weibel-based model of the human trachea and bronchi with cartilaginous rings. A transparent model and refractive index matching methods were used to observe the flow, particularly near the wall. The flow was seeded with tracers to perform particle image velocimetry and particle tracking velocimetry to quantify the effect the rings have on the flow near the trachea and bronchi walls. The experiments were carried out with a flow rate comparable with a resting state (trachea-based Reynolds number of ReD = 2650). RESULTS: The results present a previously unknown phenomenon in the cavities between the cartilaginous rings: a small recirculation is observed in the upstream side of the cavities throughout the trachea. This recirculation is due to the adverse pressure gradient created by the expansion, which traps particles within the ring cavity, thus affecting the treatment of patients suffering from lung disease and other respiratory conditions. CONCLUSIONS: The detection of recirculation zones in the cartilage ring cavities sheds light on the particle deposition mechanism and helps explain results from previous studies that have observed an enhancement of particle deposition in models with cartilage rings. These results bring to light the importance of including cartilage rings in experimental, numerical, and theoretical models to better understand particle deposition in the trachea and bronchi. In addition, the results provide scientists and medical staff with new insights for improving drug delivery. PMID- 29791263 TI - Transgender Embodiment: A Lacanian Approach. AB - The author uses Lacanian psychoanalysis to conceptualize transgender embodiment, focusing on the Lacanian concept "objet a" to analyze how transpeople may be uniquely attuned to a fundamental lack in being endemic to all subjects of language. Objet a is central to the Imaginary register where body images and sex morphology intermingle. The author discusses objet a in relation to the mirror (and the Other's cisgender gaze), anxiety, postsurgical scars, linguistics, and Thing-like feelings of monstrosity (born of transphobia). For those who are transgender, the a may register as an embodied disjunction between gender identity and natal sex assignment. PMID- 29791264 TI - The Economic Problem of Candidacy. AB - Candidates frequently accept one or multiple low-fee cases as part of their training experience. Although the practical and unconscious meanings of the formerly taboo topic of money have recently been discussed in the literature, the candidate's experience in regard to the fee is rarely discussed. The author argues that the candidate is positioned to face a Gordian knot of personal, training, and clinical intensity in the duration of training that impacts casework. This paper discusses two prototypical characterological constellations related to the fee. Psychoanalytic training involves immersion, and thereby differs from training in psychoanalytic psychotherapy programs or from a residency in psychiatry. The candidate's economic experience is unique and under recognized in today's practice climate. The present article recommends open discussion about the fee among psychoanalysts and candidates. PMID- 29791266 TI - Building Castles Made of Pleasure. AB - To outlive the suicide of one's beloved, an ineffable trauma, entails a complicated grieving process. This paper illustrates the importance of understanding body and self as malleable, invested objects. The treatment of traumatized patients involves redrawing body frontiers, and subsequent reassurance that the body, once delineated and inhabited, won't betray its host. The concepts of objet a and transitional objects help distinguish anxieties related to external loss from anxieties related to the incorporation or reabsorption of an object whose cruel proximity threatens the internal integrity of body experience. The movement toward mourning can be complicated by melancholic incorporation of the deceased, especially in cases of suicide; the volitional nature of such acts retroactively disrupts life narratives, forcing one to create new answers to questions of who and what one was for the other who chose death and to give new connotations to one's prior encounters with death. PMID- 29791268 TI - Differences in Firearm Suicides by Residential Location in Texas, 2006-2015. AB - This study used Texas state vital statistics records, 2006-2015, to examine firearm use rates among 28,010 suicide decedents by residential location (urbanized vs. all others). Firearms were responsible for 44% of all teenage suicides and 76-90% and 50-60% of suicides of men and women aged 60 + years, respectively, and firearm use rates remained steady for both genders during the study period. Logistic regression analysis showed a significantly higher firearm use rate (AOR = 1.35, 95% CI = 1.28-1.42) among decedents who resided in nonurbanized areas. Differences in firearm use rates by residential location likely reflect higher firearm ownership in smaller communities and rural than urban areas. The findings underscore the importance of community- and individual level suicide prevention strategies. PMID- 29791267 TI - Jealousy as a Driving Force for Murder. AB - This essay draws on analytic concepts and artistic examples in order to explore murder as the ultimate fate of jealousy. The paper first explores two seemingly neurotic forms of possessive fury that result in a crime of passion. Both cases probe the criminal potential of a supposedly normal subject and question the frontiers of narcissism and self-love, while discussing gender stereotypes. The author then examines criminal jealousy from the vantage point of the specular stakes at play: the enamoration of the double pervaded with aggressiveness that stems from the pre-oedipal fraternal complex and leads to outbursts of psychotic allure. Furthermore, this contribution appraises the hedonistic possibilities created by crimes of passion that are "beyond the pleasure principle." Finally, the figure of the jealous criminal is understood as a radicalization of a universal logic, according to which primary narcissistic wounds are felt to be an unbearable injustice that requires reparation through an infringement of the law. PMID- 29791269 TI - The cystic dilation of ventriculus terminalis with neurological symptoms: Three case reports and a literature review. AB - CONTEXT: The ventriculus terminalis (VT) is a very small ependymal-lined residual lumen in the conus medullaris. It is normally present in all subjects during fetal development. VT in adults appears as an unusual pathology with an uncertain pathogenesis. FINDINGS: In this paper, we described three case reports of symptomatic fifth ventricle cystic dilations. All of them were female and their mean age was 59 years. We treated them surgically and all three patients were improved based on clinical and imaging assessments. CONCLUSION: Our cases suggested that surgical decompression was a safe and effective treatment in symptomatic patients and the neurosurgeons should be aware of such rare situations. A complete list of differential diagnosis about other cystic dilations of the conus medullaris should be emphasized to select the correct clinical approach. PMID- 29791270 TI - Potential for Spread of Hand Infection after Elastic Exsanguination. PMID- 29791271 TI - Language Skills, but Not Frequency Discrimination, Predict Reading Skills in Children at Risk of Dyslexia. AB - This study evaluated the claim that auditory processing deficits are a cause of reading and language difficulties. We report a longitudinal study of 245 children at family risk of dyslexia, children with preschool language impairments, and control children. Children with language impairments had poorer frequency discrimination thresholds than controls at 5.5 years, but children at family risk of dyslexia did not. A model assessing longitudinal relationships among frequency discrimination, reading, language, and executive function skills showed that frequency discrimination was predicted by executive skills but was not a longitudinal predictor of reading or language skills. Our findings contradict the hypothesis that frequency discrimination is causally related to dyslexia or language impairment and suggest that individuals at risk for dyslexia or who have language impairments may perform poorly on auditory processing tasks because of comorbid attentional difficulties. PMID- 29791272 TI - Are Bullying Perpetration and Victimization Associated with Adolescent Deliberate Self-Harm? A Meta-Analysis. AB - This study sought to appraise internationally published literature investigating bullying in its association with deliberate self-harm (DSH). A systematic review and series of meta-analyses using random effects models were conducted. A total of 68 effect sizes, analyzing data from 156,284 adolescents aged 11-19 years were examined. Results showed significant associations between both traditional bullying perpetration (OR 1.81, 95% CI [1.33, 2.47], p < .0001) and victimization (OR 2.34, 95% CI [1.89, 2.89], p < .0001) and DSH. Cyber-bullying victimization (OR 3.55, 95% CI [2.71, 4.65], p < .0001) and the co-occurrence of traditional and cyber-bullying victimization (OR 3.39, 95% CI [1.56, 7.37], p = .002) were also associated with DSH. Moderator analyses showed variation in results based on methodological- and sample-level variables. Findings suggested that exposure to bullying, either as perpetrators or victims, poses risks for DSH. PMID- 29791273 TI - Survivorship care needs among LGBT cancer survivors. AB - OBJECTIVE: To better understand survivorship care needs among LGBT cancer survivors. DESIGN: We administered an anonymous online survey. SAMPLE: LGBT cancer survivors living in the United States. METHODS: Participants were recruited via the National LGBT Cancer Project. The survey measured sociodemographic characteristics, social support, posttraumatic stress, and survivorship care needs. RESULTS: Approximately 72% of our 114 participants were cisgender male and 87% were white. Almost all participants reported at least some unmet survivorship care needs (73%), with over half of participants reporting unmet psychological and sexuality care needs. Participants who reported their oncologist was not LGBT-competent had greater unmet needs (t(82) = 2.5, p = 0.01) and greater posttraumatic stress (t(91) = 2.1, p = 0.035). CONCLUSIONS: LGBT cancer survivors have significant unmet survivorship care needs, and lack of oncologist LGBT-competence is associated with unmet needs. Implications for Psychosocial Providers: Our results suggest the need for LGBT competency training for providers. PMID- 29791274 TI - Cathodal tDCS of the Left Posterior Parietal Cortex Increases Proprioceptive Drift. AB - In aiming movements the limb position drifts away from the defined target after some trials without visual feedback, a phenomenon defined as proprioceptive drift (PD). There are no studies investigating the association between the posterior parietal cortex (PPC) and PD in aiming movements. Therefore, cathodal and sham transcranial direct current stimulation (tDCS) were applied to the left PPC concomitantly with the performance of movements with or without vision. Cathodal tDCS applied without vision produced a higher level of PD and higher rates of drift accumulation while it decreased peak velocity and maintained the number of error corrections, not affecting movement amplitude. The proprioceptive information seems to produce an effective reference to movement, but with PPC stimulation it causes a negative impact on position. PMID- 29791276 TI - Isolating the Association of Sleep, Depressive State, and Other Independent Indicators for Suicide Ideation in United States Teenagers. AB - According to the Centers for Disease Control and Prevention, suicide is the second leading cause of death in American teenagers, and is a growing public health concern. This study uses multivariable logistic regression to investigate the independent relationship between suicide ideation and sleep duration in teenagers using the 2015 Youth Behavior Risk Surveillance Study, controlling for demographic, behavioral, and other factors found to be associated. Sleep durations of 4-5 hours and 6-7 hours per night were associated with approximately 75-80% and 20-40% increased adjusted odds of suicide ideation, as compared to teens sleeping the recommended 8 hours or more, and should be considered as a potential important indicator for adolescent suicidal ideation in primary-care screens. PMID- 29791277 TI - Peer Rejection and Internalizing Behavior: The Mediating Role of Peer Victimization in Preschool. AB - The author examined the relationship among peer rejection, peer victimization, and internalizing behaviors. The author hypothesized that physical and relational victimization would have a different indirect effect on the relationship between peer rejection and internalizing behaviors. Participants were 94 preschool children (37 girls; average age 49.97 months) from two university preschools located in the northern part of the United States. The results indicated that internalizing behaviors predicted the mediating variables only regarding relational victimization. Relational victimization indirectly affected the association between peer rejection and internalizing behaviors. The study provides evidence of the mediating effect of victimization behaviors on the relationship among peer rejection, victimization, and internalizing behaviors. PMID- 29791275 TI - Effects of web-based instruction and patient preferences on patient-reported outcomes and learning for women with advanced ovarian cancer: A randomized controlled trial. AB - A randomized controlled trial was conducted of a web-based intervention to improve advanced care planning in women with ovarian cancer. A secondary analysis of 35 randomized women focused on changes in distress and knowledge about ovarian cancer through distress monitoring and information tailored to patients' cognitive coping style (monitoring, blunting). Pre-/postresults indicated the Intervention group demonstrated lower distress (p = 0.06); blunting was associated with lower depression (p = 0.04); knowledge in both groups was unchanged. Women in the Intervention vs. Control group reported their family was less likely to be upset by cancer information (p = 0.0004). This intervention reduced distress while incorporating patient preferences. PMID- 29791278 TI - Specificity of Postural Control: Comparing Expert and Intermediate Dancers. AB - The expert-novice approach is inappropriate for studying postural control in sport and dance when novices are completely unable to perform relevant postural tasks and experts cannot demonstrate specific skills on everyday postural tasks. We tested expertise-specific differences on 6 static everyday and 5 dynamic dance like postural tasks of varying difficulty in 13 professional and 12 intermediate nonprofessional dancers. Results showed a clear expert advantage on sway area for dance-like postural tasks, but not for static everyday tasks. This effect was also found for the control parameter of root mean square (RMS) velocity and partly for RMS amplitude of the difference signal between CoP and CoG line location. Results indicate that the expert advantage is task-specific and deliver new insights into the specificity of experts' postural performance. PMID- 29791279 TI - Loneliness in senior housing communities. AB - There are many studies on loneliness among community-dwelling older adults; however, there is limited research examining the extent and correlates of loneliness among older adults who reside in senior housing communities. This study examines the extent and correlates of loneliness in three public senior housing communities in the St. Louis area. Data for this project was collected with survey questionnaires with a total sample size of 148 respondents. Loneliness was measured using the Hughes 3-item loneliness scale. Additionally, the questionnaire contained measures on socio-demographics, health/mental health, social engagement, and social support. Missing data for the hierarchical multivariate regression models were imputed using multiple imputation methods. Results showed approximately 30.8% of the sample was not lonely, 42.7% was moderately lonely, and 26.6% was severely lonely. In the multivariate analyses, loneliness was primarily associated with depressive symptoms. Contrary to popular opinion, our study found the prevalence of loneliness was high in senior housing communities. Nevertheless, senior housing communities could be ideal locations for reducing loneliness among older adults. Interventions should focus on concomitantly addressing both an individual's loneliness and mental health. PMID- 29791280 TI - The Effects of Publicized Suicide Deaths on Subsequent Suicide Counts in Israel. AB - This study investigated associations between indiscriminate media reporting of suicides and later inflated suicide counts among Israel's general population between the years 2008 and 2012. Self-inflicted deaths that received post-suicide media exposure (referred to as "publicized suicides") were selected via Google news search-hit appraisals. Distributions of suicides were inspected and risk ratios (RRs) estimated by comparing population suicide rates 4 weeks before and 4 weeks after each publicized suicide ("reference" vs. "affected" periods, respectively). Poisson time series regression was employed to account also for secular trends and seasonality. A total of 2,119 people died by suicide, 13 of whom received noticeable media attention throughout the study. No meaningful impact following the 13 deaths on subsequent suicide counts during the observation window (affected vs. reference phase) was found. Poisson regression confirmed that suicide counts following publicized suicides were independent of media coverage. Given the pronounced search hits following the publicized suicides developing regulation practices that constrain indiscreet media reporting should officially be included as part of suicide prevention practices. Future research should focus on imitation suicide effects as a function of post suicide media exposure, while including both risk and protective factors. PMID- 29791281 TI - Disparities in psychological well-being based on subjective and objective eating disorder recovery statuses, and recovery status concordance. AB - This research examines how eudaimonic psychological well-being (PWB) relates to variant levels of eating disorder (ED) recovery (full, partial, active ED), both self-defined and objectively determined, and to subjective-objective recovery status concordance. Participants (N = 132; Mage = 30.1) completed an online survey targeting ED symptomology, PWB, and recovery. MANOVAs revealed idiosyncratic relationships between recovery and PWB when objective criteria, subjective perceptions, and concordance were considered. Generally, superior levels of recovery were associated with superior PWB. PWB and clients' perceptions of recovery should be considered during treatment and in establishing a uniform definition of ED recovery. PMID- 29791283 TI - Understanding the Expanding Roles of Interferon and Cytokines in Health and Disease. PMID- 29791282 TI - Quantitation of Plasmacytoid Dendritic Cells in Chronic Hepatitis B Patients with HBeAg Positivity During PEG-IFN and Entecavir Therapy. AB - Plasmacytoid dendritic cells (pDCs) are crucial for control of chronic hepatitis B (CHB) virus infection. In this study, we evaluated the frequencies of pDCs and expression of functional molecules on pDCs in patients treated with PEG-IFN-alpha 2a or entecavir (ETV) and investigated changes during treatment. The mean fluorescence intensity of CD86 (CD86MFI) on the surface of pDCs and frequencies of pDCs and CD86+ pDCs in peripheral blood were measured. Compared with baseline, CD86+ pDC% and CD86MFI increased obviously after PEG-IFN-alpha-2a treatment for 12 and 24 weeks. For patients treated with ETV, only pDC% increased observably after treatment weeks 12 and 24 (P < 0.001) compared with baseline. Hepatitis B surface antigen (HBsAg) decline was significantly associated with elevated CD86+ pDC% (r = 0.348, P = 0.015) during PEG-IFN-alpha-2a treatment. In the HBsAg response group, CD86+ pDC% and CD86MFI (P < 0.001) increased observably after PEG IFN-alpha-2a therapy, whereas only CD86MFI had a statistically significant difference after therapy compared with baseline (12 weeks versus 0 weeks, P = 0.022; 24 weeks versus 0 weeks, P = 0.015) in the HBsAg nonresponse group. CD86+ pDC% between the 2 groups had statistically significant differences at baseline (P = 0.001) and at the treatment time points of 12 and 24 weeks (P < 0.001), respectively. For patients receiving ETV therapy, pDC% increased observably, but CD86+ pDC% decreased significantly (P < 0.001) in the HBV DNA nonresponse group during early treatment with ETV. In CHB patients, HBsAg response in PEG-IFN-alpha 2a therapy correlated with the increase of CD86+ pDC% and HBV DNA nonresponse in ETV treatment correlated with the decrease of CD86+ pDC%. PMID- 29791284 TI - Risk-Imaging Mismatch in Cardiac Imaging Practices for Women Receiving Systemic Therapy for Early-Stage Breast Cancer: A Population-Based Cohort Study. AB - Purpose To assess prechemotherapy cardiac imaging practices in relation to patients' heart failure (HF) risk. Methods We performed a population-based retrospective cohort study of women receiving chemotherapy for early-stage breast cancer in Ontario between 2007 and 2012. We surveyed for baseline cardiac imaging 6 months before chemotherapy or within 30 days thereafter. The proportion of patients who underwent imaging and cumulative incidence of major adverse cardiac event (MACE) rates was determined based on chemotherapy regimen and HF risk factors. Logistic regression was used to assess predictors of pretreatment cardiac imaging. Results We studied 18,444 women who had been treated with chemotherapy (median age, 55 years). There was near-universal imaging of women treated with trastuzumab-containing regimens, including those without additional HF risk factors. Women who received anthracyclines without trastuzumab underwent imaging more frequently if they had additional HF risk factors (73.3% v 62.6%; P < .001). The 5-year incidence of MACE was two to six times higher in patients with HF risk factors across all treatment regimens. Patients with HF risk factors who received anthracyclines without trastuzumab had a higher 5-year incidence of MACE (4.5%) than patients without HF risk factors who received trastuzumab without anthracyclines (2.6%). However, cardiac imaging was less frequent in the former group (73.3% v 93.6%; P < .001). Logistic regression indicated that most variation in baseline imaging was related to chemotherapy, followed by physician level factors. The odds of imaging were doubled with female physicians. Patient specific factors, including HF risk factors, made minimal contribution to variation in imaging. Conclusion Baseline cardiac imaging was driven by chemotherapy regimen rather than HF risk. This risk-imaging mismatch is an impetus to reconsider current cardiac imaging practices in patients who receive chemotherapy for breast cancer. PMID- 29791286 TI - Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. AB - Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer guidelines . PMID- 29791285 TI - Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data. AB - Purpose Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments. Methods For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with >= 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left sided and right-sided breast cancer were compared. Results Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( Ptrend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were -5.0, 2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( Ptrend = .002). Conclusion For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized. PMID- 29791288 TI - Strikingly Heterogeneous Results Among Studies on Interim Fluorodeoxyglucose Positron Emission Tomography-Adapted Treatment in Advanced-Stage Hodgkin Lymphoma. PMID- 29791289 TI - Minimally Invasive Lung Cancer Surgery Performed by Thoracic Surgeons as Effective as Thoracotomy. AB - Purpose The prevalence of minimally invasive lung cancer surgery using video assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients > 65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P < .001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P < .001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy. PMID- 29791287 TI - BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. AB - Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations. PMID- 29791291 TI - Additional Evidence That End-of-Treatment Fluorodeoxyglucose-Positron Emission Tomography Evaluation Is Necessary in Advanced Hodgkin Lymphoma. PMID- 29791290 TI - Reply to H.J.A. Adams et al and C. Mesguich et al. PMID- 29791292 TI - Sepsis Caused by Streptococcus suis Serotype 2 in a Eurasian River Otter ( Lutra lutra) in the Republic of Korea. AB - An adult male Eurasian river otter ( Lutra lutra) was diagnosed with systemic infection. Microbiologic findings identified Streptococcus suis serotype 2, clonal complex 28, and sequence type 629. Genetic analysis strongly suggested the transmission of S. suis isolate from pigs to wild animals through environmental contamination. PMID- 29791293 TI - Thelazia callipaeda, an Endemic Parasite of Red Foxes ( Vulpes vulpes) in Western Romania. AB - Thelazia callipaeda (Spirurida, Thelaziidae) is a vector-borne zoonotic nematode parasite of the conjunctival sac of a large spectrum of hosts, currently having an expanding distribution range throughout Europe. In Romania, the parasite has a relatively large distribution range and host spectrum. However, the presence of T. callipaeda in red foxes ( Vulpes vulpes) has not yet been confirmed. The aim of the present study was to assess the prevalence and geographical distribution of T. callipaeda in red foxes from Romania. A total of 514 animals originating from 10 counties of western Romania were evaluated for the presence of T. callipaeda. Overall, 151 red foxes (29.38%) were positive. No significant differences were noticed between sex and age groups of positive foxes. In total, 3,350 adult nematodes were recovered. The intensity of infection had a mean value of 23.2, while the sex ratio was 2.2:1 in favor of females. In 91 foxes, both eyes were affected, while 60 harbored unilateral infection. Sequence analysis of the cox 1 gene of one nematode from each positive fox ( n=151) revealed the exclusive presence of haplotype h1. We report a relatively high prevalence and distribution range of T. callipaeda infection in red foxes in Romania, highlighting their potential role as a wildlife reservoir. PMID- 29791295 TI - ULTRASONOGRAPHIC DETECTION OF INGESTED FISHING LINES IN LOGGERHEADS ( CARETTA CARETTA). AB - Loggerhead sea turtles ( Caretta caretta) are among the most frequent victims of bycatch in drifting longlines, and the ingestion of fish hooks and fishing lines is one of the most frequent causes of death of sea turtles. The aim of this study was to evaluate whether coelomic ultrasound (US) can be decisive, not only for diagnosis but also to optimize surgical planning based on preoperative evaluation of the bowel conditions and, in addition, to see if there are characteristic sonographic findings in sea turtles associated with the ingestion of fishing lines. Physical examination, hematology, blood chemistry, radiographs, and US examination were performed in 37 loggerhead sea turtles with suspected or known ingestion of fish hooks or monofilament fishing lines. During the ultrasonographic examinations, the loggerhead sea turtles were placed in dorsal recumbency and the prefemoral left and right acoustic windows were used. Nine wild loggerheads had sonographic findings of intestinal and coelomic abnormalities, and the sonographic images were compared with the surgical findings. Ultrasonography positively identified the foreign body in 89% (8/9) animals. The presence of intestinal plication (in all loggerhead turtles) and ultrasonographic visualization of the linear foreign body was always consistent with the ingestion of a fishing line. In sea turtles, fishing lines cause a corrugated appearance in the small intestine due to increased/unproductive peristalsis. The affected small bowel loops are usually dilated with fluid. In the present study, coelomic US allowed us to make a thorough evaluation of the characteristics, number, and severity of the bowel wall lesions in the animals, thus ensuring the planning of a correct surgical procedure. We suggest that US examination of the coelomic cavity should be complementary to radiographic survey in cases of suspected ingestion of fish hooks and fishing lines by sea turtles. PMID- 29791294 TI - A SURVEY OF PARASITE LESIONS IN WILD RED DEER ( CERVUS ELAPHUS) FROM ARGENTINA. AB - In Argentina there is little information about diseases that affect exotic ungulates and the health risks that they pose to native wildlife, livestock, and humans. The aim of this study was to evaluate the health status of red deer ( Cervus elaphus) in the Nahuel Huapi National Park and surrounding areas in Patagonia, Argentina. During three consecutive hunting seasons, necropsies were performed on 101 red deer, and tissues were examined histologically. The most common lesions were those associated with hepatic and pulmonary parasites. Fasciola hepatica was observed in 15 red deer and was associated with cholangiohepatitis (8%) and/or cholangitis (10%). Dictyocaulus sp. (likely Dictyocaulus eckerti) was associated with interstitial pneumonia (5%), bronchitis (5%), pulmonary emphysema (13%), and bronchus-associated lymphoid tissue hyperplasia (13%). Other findings included Sarcocystis spp. cysts in the myocardium (89%) associated with interstitial, focal, lymphoplasmacytic myocarditis (8%); periportal lymphoplasmacytic hepatitis (8%); hepatic centrilobular necrosis (6%); lymphoplasmacytic interstitial nephritis (25%); and follicular hyperplasia in mediastinal, prescapular, and prefemoral lymph nodes (86%). Our report of lesions caused by endemic parasites of livestock in free ranging exotic red deer in Patagonia sets the foundation for a health-monitoring and -surveillance system of wildlife in this region, which is essential for the sustainable management of threatened Argentinean native fauna. PMID- 29791296 TI - Attending to What and Where: Background Connectivity Integrates Categorical and Spatial Attention. AB - Top-down attention prioritizes the processing of goal-relevant information throughout visual cortex based on where that information is found in space and what it looks like. Whereas attentional goals often have both spatial and featural components, most research on the neural basis of attention has examined these components separately. Here we investigated how these attentional components are integrated by examining the attentional modulation of functional connectivity between visual areas with different selectivity. Specifically, we used fMRI to measure temporal correlations between spatially selective regions of early visual cortex and category-selective regions in ventral temporal cortex while participants performed a task that benefitted from both spatial and categorical attention. We found that categorical attention modulated the connectivity of category-selective areas, but only with retinotopic areas that coded for the spatially attended location. Similarly, spatial attention modulated the connectivity of retinotopic areas only with the areas coding for the attended category. This pattern of results suggests that attentional modulation of connectivity is driven both by spatial selection and featural biases. Combined with exploratory analyses of frontoparietal areas that track these changes in connectivity among visual areas, this study begins to shed light on how different components of attention are integrated in support of more complex behavioral goals. PMID- 29791297 TI - Late Positive Component Event-related Potential Amplitude Predicts Long-term Classroom-based Learning. AB - It is difficult to predict whether newly learned information will be retrievable in the future. A biomarker of long-lasting learning, capable of predicting an individual's future ability to retrieve a particular memory, could positively influence teaching and educational methods. ERPs were investigated as a potential biomarker of long-lasting learning. Prior ERP studies have supported a dual process model of recognition memory that categorizes recollection and familiarity as distinct memorial processes with distinct ERP correlates. The late positive component is thought to underlie conscious recollection and the frontal N400 signal is thought to reflect familiarity [Yonelinas, A. P. Components of episodic memory: The contribution of recollection and familiarity. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 356, 1363-1374, 2001]. Here we show that the magnitude of the late positive component, soon after initial learning, is predictive of subsequent recollection of anatomical terms among medical students 6 months later. PMID- 29791298 TI - The Influence of Dopamine on Cognitive Flexibility Is Mediated by Functional Connectivity in Young but Not Older Adults. AB - Dopaminergic signaling in striatum is strongly implicated in executive functions including cognitive flexibility. However, there is a paucity of multimodal research in humans defining the nature of relationships between endogenous dopamine, striatal network activity, and cognition. Here, we measured dopamine synthesis capacity in young and older adults using the PET tracer 6-[18F]fluoro-l m-tyrosine and examined its relationship with cognitive performance and functional connectivity during an fMRI study of task switching. Aging is associated with alteration in dopamine function, including profound losses in dopamine receptors but an apparent elevation in dopamine synthesis. A compensatory benefit of upregulated dopamine synthesis in aging has not been established. Across young and older adults, we found that cognitive flexibility (low behavioral switch cost) was associated with stronger task-related functional connectivity within canonical fronto-striato-thalamic circuits connecting left inferior frontal gyrus, dorsal caudate nucleus (DCA) and ventral lateral/ventral anterior thalamic nuclei. In young adults, functional connectivity mediated the influence of DCA dopamine synthesis capacity on switch cost. For older adults, these relationships were modified such that DCA synthesis capacity and connectivity interacted to influence switch cost. Older adults with most elevated synthesis capacity maintained the pattern of connectivity-cognition relationships observed in youth, whereas these relationships were not evident for older adults with low synthesis capacity. Together, these findings suggest a role of dopamine in tuning striatal circuits to benefit executive function in young adults and clarify the functional impact of elevated dopamine synthesis capacity in aging. PMID- 29791299 TI - Spatial Attention Enhances the Neural Representation of Invisible Signals Embedded in Noise. AB - Recent evidence suggests that voluntary spatial attention can affect neural processing of visual stimuli that do not enter conscious awareness (i.e., invisible stimuli), supporting the notion that attention and awareness are dissociable processes [Wyart, V., Dehaene, S., & Tallon-Baudry, C. Early dissociation between neural signatures of endogenous spatial attention and perceptual awareness during visual masking. Frontiers in Human Neuroscience, 6, 1 14, 2012; Watanabe, M., Cheng, K., Murayama, Y., Ueno, K., Asamizuya, T., Tanaka, K., et al. Attention but not awareness modulates the BOLD signal in the human V1 during binocular suppression. Science, 334, 829-831, 2011]. To date, however, no study has demonstrated that these effects reflect enhancement of the neural representation of invisible stimuli per se, as opposed to other neural processes not specifically tied to the stimulus in question. In addition, it remains unclear whether spatial attention can modulate neural representations of invisible stimuli in direct competition with highly salient and visible stimuli. Here we developed a novel EEG frequency-tagging paradigm to obtain a continuous readout of human brain activity associated with visible and invisible signals embedded in dynamic noise. Participants ( n = 23) detected occasional contrast changes in one of two flickering image streams on either side of fixation. Each image stream contained a visible or invisible signal embedded in every second noise image, the visibility of which was titrated and checked using a two interval forced-choice detection task. Steady-state visual-evoked potentials were computed from EEG data at the signal and noise frequencies of interest. Cluster based permutation analyses revealed significant neural responses to both visible and invisible signals across posterior scalp electrodes. Control analyses revealed that these responses did not reflect a subharmonic response to noise stimuli. In line with previous findings, spatial attention increased the neural representation of visible signals. Crucially, spatial attention also increased the neural representation of invisible signals. As such, the present results replicate and extend previous studies by demonstrating that attention can modulate the neural representation of invisible signals that are in direct competition with highly salient masking stimuli. PMID- 29791300 TI - Which Chart Elements Accurately Identify Emergency Department Visits for Suicidal Ideation or Behavior? AB - OBJECTIVE: In an emergency department (ED) sample, we investigated the concordance between identification of suicide-related visits through standardized comprehensive chart review versus a subset of three specific chart elements: ICD 9-CM codes, free-text presenting complaints, and free-text physician discharge diagnoses. METHODS: Review of medical records for adults (>=18 years) at eight EDs across the United States. RESULTS: A total of 3,776 charts were reviewed. A combination of the three chart elements (ICD-9-CM, presenting complaints, and discharge diagnoses) provided the most robust data with 85% sensitivity, 96% specificity, 92% PPV, and 92% NPV. CONCLUSIONS: These findings highlight the use of key discrete fields in the medical record that can be extracted to facilitate identification of whether an ED visit was suicide-related. PMID- 29791301 TI - The Significance of Interleukin-6 in the Early Detection of Surgical Site Infections after Definitive Operation for Gastrointestinal Fistulae. AB - BACKGROUND: Surgical site infections (SSIs) are among the most common complications after definitive treatment for intestinal fistulae. Serum inflammatory markers including white blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), as well as procalcitonin (PCT) have been used to help diagnosis post-operative complications. OBJECTIVE: The goal of this study was to assess the clinical value of inflammatory markers, specifically IL-6, in predicting SSIs after intestinal fistulae resection. METHODS: A total of 184 consecutive patients who underwent elective intestinal fistula resection were enrolled prospectively. All patients were screened to exclude patients with existing clinical infection. Plasma IL-6 concentrations, serum PCT, and CRP concentrations were measured pre-operatively and on post-operative days one, three, and seven. The predictive value of each laboratory marker for SSI was calculated. RESULTS: The incidence of SSI after elective intestinal fistula resection was 26.7%. Interleukin-6, PCT, and CRP concentrations were higher in patients with SSIs compared with patients without. In contrast, there was no statistical difference for WBC counts between the two groups. Receiver operating characteristic curves demonstrated that IL-6 had the highest diagnostic effectiveness for post-operative SSI on post-operative day one, with an area under the curve of 0.77, and a sensitivity of 85.7% and specificity of 63.9%. CONCLUSION: A concentration of IL-6 above 95.6 ng/L on post-operative day one and 52.5 ng/L on post-operative day three, and a concentration of PCT exceeding 0.61 mcg/L predict the occurrence of SSI after definitive operations for gastrointestinal fistulae. PMID- 29791302 TI - Preferences of adults with spinal cord injury for widely used health-related quality of life and subjective well-being measures. AB - OBJECTIVE: To describe preferences for survey instruments on health-related quality of life (HRQOL) and subjective well-being (SWB) among adults with spinal cord injury (SCI), and compare perspectives on the instruments between the United States and the United Kingdom. DESIGN: We conducted 20 in-depth interviews. SETTING: Participants were interviewed in their homes, some in person and some via Skype. PARTICIPANTS: A convenience sample of 20 adults with SCI (10 in the US and 10 in the UK) were recruited via print and on-line advertisements. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interviewees reviewed six instruments and rated how important it was for their medical providers to know answers to each survey. Two coders analyzed verbatim transcriptions independently using an inductive approach. Keyword-in-context (KWIC) analysis identified the most frequently used words by interviewees to discuss the merits of each instrument. RESULTS: Participants in both samples identified the Fatigue Severity Scale (FSS) as "vital" that their medical providers know about it. This was followed by the Spinal Cord Injury Independence Measure III, and a stand-alone Eudaimonic Well-Being question. The KWIC analysis showed that the most distinctive words used to discuss FSS were "fatigue" and "pain." CONCLUSIONS: Understanding what HRQOL and SWB measures are valued by adults living with SCI can lead to selection of informative instruments, which could help clinicians to complement and tailor established care and rehabilitation protocols for individual needs. Participants identified fatigue as a significant issue, and the FSS as a vitally important instrument to share with medical providers. PMID- 29791303 TI - Suicide Timing in 18 States of the United States from 2003-2014. AB - OBJECTIVES: We investigated suicide timing over different time periods by age, sex and race/ethnicity. METHODS: 122,107 suicide deaths were identified from the population-based U.S. National Violent Death Reporting System in 18 U.S. States from 2003 through 2014. RESULTS: Suicides significantly increased (p < 0.05) from March to peak in September before falling, the first week of the month, and early in the week. Suicides also significantly increased (p < 0.05) in the morning, mainly peaking during the afternoon, although suicides in adolescents peaked in the evening and in those 65 years and older peaked in the morning. CONCLUSIONS: Comprehensive prevention efforts should focus on those at overall increased suicide risk and at peaks of high suicide frequency, especially among those vulnerable subgroups. PMID- 29791304 TI - Common Pathways to NSSI and Suicide Ideation: The Roles of Rumination and Self Compassion. AB - We investigated whether rumination and self-compassion moderate and/or mediate the relationships between negative affect and both non-suicidal self-injury (NSSI) and suicide ideation. Undergraduate university students (n = 415) completed well-validated measures of negative affect, rumination, self compassion, NSSI, and suicide ideation. Neither rumination nor self-compassion moderated associations between negative affect and NSSI and suicide ideation. However, both rumination and self-compassion mediated associations between negative affect and lifetime history of NSSI and suicide ideation. Self compassion additionally mediated the association between negative affect and both 12-month NSSI and suicide ideation. The salience of self-compassion, particularly in predicting recent NSSI and suicide ideation, offers promise for early intervention initiatives focusing on less judgmental or self-critical means of self-relation. PMID- 29791305 TI - Commercial Frozen Mice Used by Owners to Feed Reptiles are Highly Externally Contaminated with Salmonella Enteritidis PT8. AB - Salmonella remains one of the most prevalent zoonoses worldwide. Although salmonellosis is commonly associated with the consumption of contaminated food, it has been estimated that up to 11% of Salmonella infections overall are acquired from direct or indirect contact with animals, including reptiles. In 2016, an outbreak of Salmonella Enteritidis involving multiple cases, especially children, associated with reptile contact and contaminated feeder mice was reported in the United Kingdom. The aim of this study was to investigate Salmonella external and internal contamination of stored commercial frozen feeder mice used to feed reptiles and obtained from the same supplier involved in the outbreak. In this study a total of 295 mice were tested (60 pinkies, 60 fuzzies, 60 small, 60 large, and 55 extra large). In this study, both external (integument) and internal (selected organs) contamination were evaluated. Salmonella Enteritidis PT8 and PT13 were isolated from 28.8% (n = 17) of the 59 batches tested, with the exception of the large mice category. Positive mice were mostly contaminated externally (92.3% vs. 26.9% for carcass wash and viscera, respectively). All isolates were sensitive to all 16 antimicrobials tested. The high level of external contamination of the rodent carcasses might have played a role in the human outbreak in 2016. Reptile owner management of the rodent carcasses at home could be an important source of salmonellosis outbreaks. Collaboration among public health officials, pet industry, veterinarians, and reptile owners is needed to help prevent the risk of salmonellosis associated with animal-based food intended for reptiles. PMID- 29791306 TI - Cause of Caregiver Death and Surviving Caregiver Coping Style Predict Thwarted Belongingness in Bereaved Youth. AB - Both bereavement and thwarted belongingness serve as risk markers for youth suicide-related behaviors. This study examined candidate predictors of thwarted belongingness among bereaved youth, including caregiver cause of death and surviving caregiver coping style. A group of 43 caregiver-bereaved families (58 children aged 7-13-years-old) participated in a longitudinal study investigating associations between hypothesized bereavement-related contextual factors and youth thwarted belongingness. Cause of caregiver deaths included anticipated deaths preceded by illness (37%; n = 16), sudden natural deaths (25.6%; n = 11), accidental deaths (20.9%; n = 9), death by suicide (9.3%; n = 4), and death from drug overdose (7.0%; n = 3). Children's thwarted belongingness was significantly higher among youth bereaved by suicide compared to youth bereaved by sudden natural death, accident, and anticipated death by illness. Surviving caregivers' use of behavioral disengagement and positive reinterpretation and growth as coping strategies at Time 1 predicted lower thwarted belongingness in children at Time 2. Implications for risk screening and assessment of suicide risk among bereaved youth are discussed. PMID- 29791307 TI - Symptomatic pneumocephalus: A rare complication of discal herniation's surgery. AB - Context We report the case of a 40-year-old woman with no pathological history, operated from an L4-L5 disc herniation by a left unilateral approach. The dura mater enveloping the left L5 root was accidentally injured at its lateral face causing a breach with CSF leakage. This breach could not be sutured. A few hours after waking, the patient presented an agitation followed by three generalized tonico-clonic seizures. Cerebral imaging revealed pneumocephalus. The patient was hospitalized in an intensive care unit. The symptoms gradually faded and the patient was discharged 3 days after surgery. Findings Pneumocephalus is defined by the presence of air inside the skull. The symptoms of pneumocephalus are generally non-specific and varied, and this complication should also be kept in mind to prevent potentially severe course. The prevention of postoperative pneumocephalus depends on a well-defined strategy in the case of iatrogenic dural tear. Conclusions Symptomatic pneumocephalus is a very rare complication in the course of lumbar surgery. Conservative therapy may be appropriate even in severe symptomatic manifestations. PMID- 29791308 TI - Optimal level and order detection in wavelet decomposition for PCG signal denoising. AB - The recorded phonocardiogram (PCG) signal is often contaminated by different types of noises that can be seen in the frequency band of the PCG signal, which may change the characteristics of this signal. Discrete wavelet transform (DWT) has become one of the most important and powerful tools of signal representation, but its effectiveness is influenced by the issue of the selected mother wavelet and decomposition level (DL). The selection of the DL and the mother wavelet are the main challenges. This work proposes a new approach for finding an optimal DL and optimal mother wavelet for PCG signal denoising. Our approach consists of two algorithms designed to tackle the problems of noise and variability caused by PCG acquisition in a real clinical environment for different categories of patients. The results obtained are evaluated by examining the coherence analysie (Coh) correlation coefficient (Corr) and the mean square error (MSE) and signal-to noise ratio (SNR) in simulated noisy PCG signals. The experimental results show that the proposed method can effectively reduce noise. PMID- 29791309 TI - Retraction of: External Quality Assessment Programs in the US with an emphasis on urinary sediment testing: the College of American Pathologists experience. PMID- 29791310 TI - Ways of Knowing as a Framework for Developing Reflective Practice among Nursing Students. AB - : Abstract Background:Nursing students face the challenge of developing a comprehensive understanding of the complex role of the registered nurse across various clinical settings. Frameworks such as the "ways of knowing", help students conceptualize and critically reflect upon important processes in their professional learning. However, the academic language used to describe frameworks can be challenging. PURPOSE: This manuscript has two purposes. First, to briefly describe the historical climate influencing the development of nursing as a discipline. Second, two clinical practicum scenarios in acute care and community based care are explored with the application of Carper's four fundamental ways of knowing in nursing (empirical, aesthetic, self-knowledge, ethical), and Chinn and Kramer's fifth, emancipatory, knowing as foundational to developing reflexivity in clinical practice. CONCLUSION: These practical descriptions and concrete examples can assist students in incorporating the five ways of knowing into their reflective practice and thereby more fully develop their construct of nursing. PMID- 29791311 TI - Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury. AB - Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean +/- SD and significance was set at p<=0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility. PMID- 29791312 TI - African crocus (Curculigo pilosa) and wonderful kola (Buchholzia coriacea) seeds modulate critical enzymes relevant to erectile dysfunction and oxidative stress. AB - Background The seeds of African crocus (AC) (Curculigo pilosa) and wonderful kola (WK) (Buchholzia coriacea) are commonly used in folklore medicine in managing erectile dysfunction (ED) without the full understanding of the possible mechanism of actions. This study investigated and compared the effects of aqueous extracts from the seeds of AC and WK on arginase and acetylcholinesterase (AChE) activities and some pro-oxidant [FeSO4 and sodium nitroprusside (SNP)]-induced lipid peroxidation in rat penile homogenate in vitro. Method Aqueous extracts of AC and WK were prepared, and their effects on arginase and AChE activities as well as FeSO4- and SNP-induced lipid peroxidation in rat penile homogenate were assessed. Furthermore, phenolic constituents of the extract were determined using high-performance liquid chromatography coupled with diode-array detector (HPLC DAD). Results Both extracts exhibited concentration-dependent inhibition on arginase (AC, IC50=0.05 mg/mL; WK, IC50=0.22 mg/mL) and AChE (AC, IC50=0.68 mg/mL; WK, IC50=0.28 mg/mL) activities. The extracts also inhibited FeSO4- and SNP-induced lipid peroxidation in rat penile homogenate. HPLC-DAD analysis revealed the presence of phenolic acids (gallic, caffeic, ellagic and coumaric acids) and flavonoids (catechin, quercetin and apigenin) in AC and WK. AC had higher arginase inhibitory and antioxidative activities but lower AChE inhibitory properties when compared with WK. Conclusions These effects could explain the possible mechanistic actions of the seeds in the management/treatment of ED and could be as a result of individual and/or synergistic effect of the constituent phenolic compounds of the seeds. PMID- 29791313 TI - Acute and subacute toxicity of aqueous extract of the tuber of Kedrostis africana (L.) Cogn in Wistar rats. AB - Kedrostis africana (L.) Cogn (Cucurbitaceae) is used in South African traditional medicine and pharmacopoeia as an emetic, purgative and diuretic, and it is used against dropsy in the management of obesity. Aim of the study In this study, acute and subacute toxicity of aqueous extract of K. africanatuber was evaluated in male and female Wistar rats in order to assess its safety profile. Materials and methods In acute toxicity, the effects of a single oral dose (2,000 and 5,000 mg/kg) of aqueous extract was determined in both sexes. General behavior, adverse effects and mortality were determined for 3 h and then periodically for 14 days. The subchronic toxicity test was performed in rats. The effects of the extract in daily single oral administration at the doses of 200, 400 and 600 mg/kg for 28 days were determined. Food and water intakes were monitored daily while body weight was monitored on a weekly bases. Hematological, biochemical and organ parameters were determined at the end of the 28-day administration. Results In the acute study, a single administration of the aqueous extract at the doses of 2,000 and 5,000 mg/kg did not induce mortality. Thus, the LD50 of the aqueous extract of K. africana (AEKA) has been estimated to be higher than 5,000 mg/kg. In the subchronic study, daily oral administration of the AEKA did not result in death of the rats or significant changes in hematological or biochemical parameters at the highest dose of 600 mg/kg. No alteration was observed in body weight, food and water intake. Liver, kidney and heart histopathology did not reveal morphological alteration. Conclusions The results showed that the aqueous tuber extract of K. africana did not cause any death, nor did it cause abnormalities in necropsy and histopathology findings. There were no acute or subchronic toxicity observed, and this indicates that the plant extract could be considered safe for oral medication. PMID- 29791314 TI - Analgesic, anti-inflammatory and anti-arthritic properties of aqueous and methanolic stem bark extracts from Nauclea pobeguinii (Rubiacee) in rats. AB - Background Nauclea pobeguinii is a plant species found in the centre region of Cameroon. The stem bark of this plant is traditionally used to ease pain and cure inflammation. Method This study was undertaken to evaluate the effects of doses 150 and 300 mg/kg of the aqueous and methanolic stem bark extracts from Nauclea pobeguinii on acute pain, acute and chronic inflammation induced by formalin and arthritis induced by zymosan A in rats. Oxidative stress parameters such as catalase, malondialdehyde and nitric oxide were measured in rats subjected to chronic inflammation. The standard used was diclofenac at 5 mg/kg. Results Aqueous extract as well as methanolic extract of Nauclea pobeguinii led to a significant reduction in the second phase of formalin induced pain with 54.22 and 48.02% of inhibition percentage, respectively. The formalin-induced inflammatory oedema was reduced by both extracts, and this effect remains significant until the tenth day of treatment. Equally, extracts significantly increased the catalase activity and inhibited the production of malondialdehyde (MDA) in serum, brain and spinal cord and NO reduction only in serum. Both extracts significantly reduced the articular oedema induced by zymosan A for 6 h and for 5 days. Furthermore, the histological study of the articulations shows a non-altered synovial membrane and a small cartilage in all treated animals versus negative control group. Conclusions From these results, it can be concluded that pain, inflammation and arthritic healing activities of both stem bark extracts were expressed in rats and could conciliate the use of this vegetable by traditional African healers. PMID- 29791316 TI - Roles of the exon junction complex components in the central nervous system: a mini review. AB - The exon junction complex (EJC) consists of four core proteins: Magoh, RNA binding motif 8A (Rbm8a, also known as Y14), eukaryotic initiation factor 4A3 (eIF4A3, also known as DDX48), and metastatic lymph node 51 (MLN51, also known as Casc3 or Barentsz), which are involved in the regulation of many processes occurring between gene transcription and protein translation. Its main role is to assemble into spliceosomes at the exon-exon junction of mRNA during splicing. It is, therefore, a range of functions concerning post-splicing events such as mRNA translocation, translation, and nonsense-mediated mRNA decay (NMD). Apart from this, proteins of the EJC control the splicing of specific pre-mRNAs, for example, splicing of the mapk transcript. Recent studies support essential functions of EJC proteins in oocytes and, after fertilization, in all stages of zygote development, as well as the growth of the embryo, including the development of the nervous system. During the development of the central nervous system (CNS), the EJC controls mitosis, regulating both symmetric and asymmetric cell divisions. Reduced levels of EJC components cause microcephaly. In the adult brain, Y14 and eIF4A3 appear to be involved in synaptic plasticity and in learning and memory. In this review, we focus on the involvement of EJC components in brain development and its functioning under normal conditions. PMID- 29791318 TI - The inhibitors - a challenge for the management of patients with hereditary haemophilia A. AB - INTRODUCTION: Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management. METHODS: Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included "haemophilia A", "inhibitors", "plasma-derived factor VIII" and "recombinant factor VIII". RESULTS: The risk factors for inhibitors occurrence may be patients-related (genetic and nongenetic) and treatment related. The possibility of a correlation between the increased purity of factor VIII given as substitution treatment and the occurrence of inhibitors is discussed in the light of literature data. Plasma-derived factor VIII is less immunogenic, but not entirely safe from the point of view of the possibility of transmitting biological agents. It is obvious that there is not enough plasma derived factor VIII for the planet's needs. Recombinant factor VIII products have revolutionized the treatment of patients with haemophilia A over the past 3 decades by the disappearance of transfusion-related infections and their complications. They are safer in terms of pathogens and the new long-acting factor VIII products are based on recombinant DNA technology. CONCLUSION: Plasma derived or recombinant factor VIII products must co-exist on the market for the benefit of haemophilic patients. Future solutions could be: less immunogenic factor VIII products, nonfactor replacement strategies, or bispecific antibody that mimics the function of coagulation factor VIII. PMID- 29791319 TI - Malignancy in a retrospective cohort of 17 patients with Dermatomyositis or Polymyositis in southern Tunisia. AB - INTRODUCTION: The prognosis of dermatomyositis (DM)/ polymyositis (PM) in adults is partly related to their association with neoplasia. The aim of our study was to report the epidemiologic, clinical, paraclinical, therapeutic and evolutionary aspects of DM associated with malignancy in patients from Sfax, south eastern of Tunisia. METHODS: A retrospective cohort study of patients with DM or PM admitted in Dermatology and Internal Medicine Departments of Hedi Chaker University Hospital of Sfax between 1996 and 2015. Cases of DM or PM associated with malignancy were retained. RESULTS: Seventeen cases (13.5%) of DM or PM associated with malignancy were noted. Fourteen patients had DM and 3 patients had PM. The Sex ratio M / F was 0.3 and the mean age at diagnosis was 56.5 years. In DM patients, malignancy preceded the myositis in 64.2% of cases. In PM patients, only one patient was known to have breast cancer and the myositis revealed the cancer for 2 others. Treatment consisted of corticosteroids associated with methotrexate in 4 cases. Outcome was fatal in 5 cases (29.4%), due to the underlying cancer in 3 cases. Swallowing disorders related to DM/PM were responsible for death in 2 cases. CONCLUSION: There are no specific clinical or biological features in paraneoplastic DM. In our series, breast neoplasm represented the first cancer associated with DM. Cancers of nasopharynx, colon and urinary tract had the second position. PMID- 29791320 TI - Modelling the cerebral haemodynamic response in the physiological range of PaCO2. AB - OBJECTIVE: Arterial CO2 (PaCO2) has a strong effect on cerebral blood flow (CBF), but its influence on CBF regulatory mechanisms and circulatory systemic variables has not been fully described over the entire physiological range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in 45 healthy volunteers (19 male, mean age 37.5 years, range 21-71) at baseline, and in response to hypo- (-5 mm Hg and -10 mm Hg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: CBFV, cerebral dynamic autoregulation index (ARI), heart rate (HR), arterial blood pressure (ABP), critical closing pressure (CrCP) and resistance-area product (RAP) changed significantly (all p < 0.0001) for hypo- and hyper-capnia. These parameters were shown to follow a logistic curve relationship representing a 'dose-response' curve for the effects of PaCO2 on the cerebral and systemic circulations. The four logistic model parameters describing each 'dose-response' curve were specific to each of the modelled variables (ANOVA p < 0.0001). SIGNIFICANCE: The ability to model the CBFV, ARI, HR, ABP, CrCP and RAP dependency of PaCO2 over its entire physiological range is a powerful tool for physiological and clinical studies, including the need to perform adjustments in disease populations with differing values of baseline PaCO2. PMID- 29791317 TI - Romanian Registry of Hypertrophic Cardiomyopathy - overview of general characteristics and therapeutic choices at a national level. AB - INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a disease with increased left ventricular (LV) wall thickness not solely explained by abnormal loading conditions, with great heterogeneity regarding clinical expression and prognosis. The aim of the present study was to collect data on HCM patients from different centres across the country, in order to assess the general characteristics and therapeutic choices in this population. METHODS: Between December 2014 and April 2017, 210 patients from 11 Romanian Cardiology centres were enrolled in the National Registry of HCM. All patients had to fulfil the diagnosis criteria for HCM according to the European Society of Cardiology guidelines. Clinical, electrocardiographic, imaging and therapeutic characteristics were included in a predesigned online file. RESULTS: Median age at enrolment was 55 +/- 15 years with male predominance (60%). 43.6% of the patients had obstructive HCM, 50% non obstructive HCM, while 6.4% had an apical pattern. Maximal wall thickness was 20.3 +/- 4.8 mm (limits 15-37 mm) while LV ejection fraction was 60 +/- 8%. Heart failure symptoms dominated the clinical picture, mainly NYHA functional class II (51.4%). Most frequent arrhythmias were atrial fibrillation (28.1%) and non sustained ventricular tachycardia (19.9%). Mean sudden cardiac death risk score (SCD-RS) was 3.0 +/- 2.3%, with 10.4% of the patients with high risk of SCD. However, only 5.7% received an ICD. Patients were mainly treated with beta blockers (72.9%), diuretics (28.1%) and oral anticoagulants (28.6%). Invasive treatment of LVOT obstruction was performed in a small number of patients: 22 received myomectomy and 13 septal ablation. Cardiac magnetic resonance was reported in only 14 patients (6.6%). CONCLUSIONS: The Romanian registry of HCM illustrates patient characteristics at a national level as well as the gaps in management which need improvement - accessibility to high-end diagnostic tests and invasive methods of treatment. PMID- 29791315 TI - Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis. AB - Objective To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. Methods We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Results Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of <=3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Conclusion Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis. PMID- 29791321 TI - Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients. AB - OBJECTIVE: It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. APPROACH: A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger-ear, PATf-e; toe-finger, PATt-f; and toe-ear PATt-e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. MAIN RESULTS: After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt-e and PATt-f measurements, with median values of 150 ms versus 172 ms in the HC group (p = 0.02), and 104 ms versus 118 ms in the HC group (p = 0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. SIGNIFICANCE: This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation. PMID- 29791322 TI - A low-complexity algorithm for detection of atrial fibrillation using an ECG. AB - OBJECTIVES: We present a method for automatic processing of single-lead electrocardiogram (ECG) with duration of up to 60 s for the detection of atrial fibrillation (AF). The method categorises an ECG recording into one of four categories: normal, AF, other and noisy rhythm. For training the classification model, 8528 scored ECG signals were used; for independent performance assessment, 3658 scored ECG signals. APPROACH: Our method was based on features derived from RR interbeat intervals. The features included time domain, frequency domain and distribution features. We assessed the performance of three different classifiers (linear and quadratic discriminant analysis, and quadratic neural network (QNN)) on the training set using 100-fold cross-validation. The QNN was selected as the highest performing classifier, and a further performance assessment on the test data made. MAIN RESULTS: On the test set, our method achieved an F1 score for the normal, AF, other and noisy classes of 0.90, 0.75, 0.68 and 0.32, respectively. The overall F1 score was 0.78. SIGNIFICANCE: The computational cost of our algorithm is low as all features are derived from RR intervals and are processed by a single hidden layer neural network. This makes it potentially suitable for low-power devices. PMID- 29791324 TI - Unimorph mirror for adaptive optics in space telescopes. AB - This paper presents a unimorph deformable mirror intended to be used as secondary corrector in space telescopes. The deformable mirror consists of a single-crystal silicon wafer (76.2 mm diameter, 500 MUm thickness) covered with an optical coating on the front side and an array of 25 independent piezoelectric transducer (PZT) actuators acting in d31 mode on the back side. The mirror is mounted on an isostatic support with three position linear actuators controlling the rigid-body motion. The first part of the paper presents the experimental results obtained with the manufactured prototype. The mirror was tested in terms of root mean square (RMS) wavefront error, open-loop long-term stability, voltage budget for active control, rigid-body actuation, reflectivity, and dynamic response. The prototype is fully compliant with the requirements set by the European Space Agency (ESA). The second part of the paper, purely based on numerical simulations, presents a robust way to face thermal distortion, inherent to unimorph architecture. PMID- 29791323 TI - Male and Female Characteristics of Facial Soft Tissue Thickness in Different Orthodontic Malocclusions Evaluated by Cephalometric Radiography. AB - BACKGROUND The facial profile is determined by the facial soft tissue thickness (FSTT) and dentoskeletal characteristics. The aim of this study was to compare male and female characteristics of FSTT in different orthodontic malocclusions using cephalometric radiography. MATERIAL AND METHODS One hundred and twenty lateral cephalometric radiography-derived cephalograms of adult male (n=47) and female (n=73) orthodontic patients, aged between 16-22 years were classified according to their dentoskeletal relationships as Class I (n=30), Class II Division 1 (n=30), Class II Division 2 (n=30), Class III (n=30). Burstone analysis of seven linear dimensions of FSTT was used. RESULTS Men had a thicker FSTT in dentoskeletal relationships Class I, Class II Division 2, and Class III. Sex differences varied from significant (t=2.056; p<0.05) for the sub-nasal area in Class II Division 2, to highly significant (t=3.772; p<0.001) for the upper lip sulcus in Class II Division 2. Women in Class II Division 1 had significantly thicker FSTT in the lower jaw area (t=2.800; p<0.01) and for the lower lip sulcus and the chin area (t=3.961; p<0.001). CONCLUSIONS Men with orthodontic malocclusions were characterized by thicker facial soft tissue compared with female patients in Class I and Class II Division 2; female patients in Class II Division 1 were characterized by thicker facial soft tissue of the mentolabial sulcus and chin. Men and women with a skeletal jaw relationship in Class III showed no significant difference in their FSTT. PMID- 29791325 TI - Design of an ultrasensitive SPR biosensor based on a graphene-MoS2 hybrid structure with a MgF2 prism. AB - We propose, to the best of our knowledge, a new configuration of a biosensor based on the graphene-MoS2 hybrid structure by adopting the lower refractive index MgF2 prism in order to improve the sensitivity and the figure of merit (FOM). We can obtain an ultrasensitive sensor with values of sensitivity and FOM as high as 540.8 degrees /RIU and 145/RIU, respectively, by modulating the parameters in the configuration and comparatively choosing a different absentee layer material. The proposed structure is applicable in the realization of an integrated device for the surface plasmon resonance biosensor. PMID- 29791326 TI - Gamma and gamma-coupled beams. AB - A new class of scalar, rotationally symmetric Gaussian-like beams is introduced. The slowly varying amplitudes of such beams are represented as analytical solutions to the paraxial wave equation, described in terms of the incomplete gamma functions and their products with quadratic exponential and power functions of different kinds. The specific functional forms of these solutions give rise to such names as gamma, gamma-Gaussian, gamma-parabolic, and gamma-anti-Gaussian beams. It is established that, within a focal volume specified by a waist size and the depth of field of about three Rayleigh lengths of the fundamental Gaussian beam of the same waist size, the parametrically optimized zero-order gamma and gamma-coupled beams possess more stabilized transverse sizes, very weak transverse irradiance sidelobes, more uniform axial irradiance distributions, and more steep controllable fall-offs of the last distributions relative to those that are inherent in the above fundamental Gaussian beam and the Bessel-Gauss beams with linear and quadratic radial dependence and the same waist size. PMID- 29791327 TI - Signature of phase singularities in diffusive regimes in disordered waveguide lattices: interplay and qualitative analysis. AB - Coexistence and interplay between mesoscopic light dynamics with singular optics in spatially disordered waveguide lattices are reported. Two CW light beams of a 1.55 MUm operating wavelength are launched as inputs to 1D waveguide lattices with controllable weak disorder in a complex refractive index profile. Direct observation of phase singularities in the speckle pattern along the length is numerically demonstrated. Quantitative analysis of the onset of such singular behavior and diffusive wave propagation is analyzed for the first time, to the best of our knowledge. PMID- 29791328 TI - Silicon microsphere whispering gallery modes excited by femtosecond-laser inscribed glass waveguides. AB - We report on the coupling of whispering gallery modes in a 500-MUm-radius silicon microsphere to a femtosecond-laser-inscribed glass optical waveguide. The shallow glass waveguide with a large mode field diameter in the near-infrared is written at a depth of 25 MUm below the glass surface, resulting in a high excitation impact parameter of 525 MUm for the microsphere. The excited whispering gallery modes of the silicon microsphere have quality factors of approximately 105 in the 90 degrees elastic scattering and 0 degrees transmission. Integration of such spherical silicon microresonators on femtosecond-laser-inscribed glass waveguides is promising for photonic communication, computation, and sensing applications. PMID- 29791329 TI - Polarization-insensitive, ultra-broadband, and compact metamaterial-inspired optical absorber via wide-angle and highly efficient performances. AB - Because of exhibiting extraordinary features, metamaterial absorbers have captured considerable attention in recent years, especially at visible frequencies. In this paper, a new design of a metamaterial-inspired perfect visible absorber (MIPVA) is investigated, which exhibits ultra-broadband, polarization-independent, and wide-angle performances. The proposed MIPVA provides a flat and near unity absorbance (>99%) in an ultra-broad range of radiation wavelengths from lambda=500 to 625 nm, while retaining its convincing absorptivity over the entire visible wavelengths. A comprehensive parametric study is accomplished to demonstrate the effects of structural parameters on the absorptivity of the designed MIPVA. To clarify the physical mechanism of absorption, the electric field and surface current distributions of MIPVA are also monitored and elaborately discussed throughout the paper. The results show that the proposed MIPVA exhibits a polarization-insensitive absorption behavior in a wide range of incident wave angles. The interference theory is also utilized to verify the results. In addition, our MIPVA has a compact and low-profile design, while its ability to absorb solar radiation is significantly improved with respect to preceding studies in terms of both the frequency bandwidth and absorptivity; thereby, it is a worthy candidate to play an essential role in different visible-range applications. PMID- 29791330 TI - Quantitative measurement of thin phase objects: comparison of speckle deflectometry and defocus-variant lateral shear interferometry. AB - The two techniques of lateral shear interferometry and speckle deflectometry are analyzed in a common optical system for their ability to measure phase gradient fields of a thin phase object. The optical system is designed to introduce a shear in the frequency domain of a telecentric imaging system that gives a sensitivity of both techniques in proportion to the defocus introduced. In this implementation, both techniques successfully measure the horizontal component of the phase gradient field. The response of both techniques scales linearly with the defocus distance, and the precision is comparative, with a random error in the order of a few rad/mm. It is further concluded that the precision of the two techniques relates to the transverse speckle size in opposite ways. While a large spatial coherence width, and correspondingly a large lateral speckle size, makes lateral shear interferometry less susceptible to defocus, a large lateral speckle size is detrimental for speckle correlation. The susceptibility for the magnitude of the defocus is larger for the lateral shear interferometry technique as compared to the speckle deflectometry technique. The two techniques provide the same type of information; however, there are a few fundamental differences. Lateral shear interferometry relies on a special hardware configuration in which the shear angle is intrinsically integrated into the system. The design of a system sensitive to both in-plane phase gradient components requires a more complex configuration and is not considered in this paper. Speckle deflectometry, on the other hand, requires no special hardware, and both components of the phase gradient field are given directly from the measured speckle deformation field. PMID- 29791331 TI - Investigation on surface/subsurface deformation mechanism and mechanical properties of GGG single crystal induced by nanoindentation. AB - In this paper, nanoindentation tests of GGG single crystal are performed on an Agilent G200 nanoindenter. The surface morphology and subsurface deformation mechanism induced by the nanoindentation are analyzed by a scanning electron microscope and a transmission electron microscope (TEM), respectively. The ductile deformation mechanism of GGG single crystal induced by the nanoindentation is a combination of "polycrystalline nanocrystallites" and "amorphous transformation." In addition, the relationships between the normal force and elastic recovery, microhardness, elastic modulus, and fracture toughness of GGG single crystal are researched. Due to the size effect caused by the tip radius of the indenter, the elastic recovery rate and fracture toughness decrease first and then tend to be stable as the normal force increases, while the microhardness and elastic modulus increase first and then decrease to be stable as the normal force increases. The stress-strain curve of GGG single crystal is developed by using the nanoindentation test with a spherical indenter. When GGG single crystal deforms from the elastic regime into the ductile regime, the original single crystal is changed into "polycrystalline nanocrystallites" and "amorphous transformation" structures verified by TEM. Therefore, the material strength decreases, which results in a discontinuity of the stress strain curve for GGG single crystal. PMID- 29791332 TI - Polarization-dependent wide-angle color filter incorporating meta-dielectric nanostructures. AB - A metadielectric nanostructure with narrow cavities is proposed, behaving as a reflective color filter for TM-polarized light while as a broadband reflector for TE-polarized light. By varying the cavity depth or changing the incident light polarization, reflective colors of the proposed structure cover the entire visible spectrum conveniently. In particular, the reflections of this proposed structure show good angular tolerance up to 50 degrees for both polarizations. Furthermore, it can display colors even with two grating slits, which shows high printing resolution up to 70555 dpi, having great potential for applications of a large area color imaging and anticounterfeiting devices. PMID- 29791333 TI - Modeling of microjoule and millijoule energy LIDARs with PMT/SiPM/APD detectors: a sensitivity analysis. AB - This paper demonstrates a renewed concept and applications of the generalized methodology for atmospheric light detection and ranging (LIDAR) capability prediction as a continuation of a series of our previous works, where the dimensionless parameterization appeared as a tool for comparing systems of a different scale, design, and applications. The modernized concept applied to microscale and milliscale LIDARs with relatively new silicon photomultiplier detectors and traditional photomultiplier tube and avalanche photodiode detectors allowed prediction of the remote sensing instruments' performance and limitations. Such a generalized, uniform, and objective concept is applied for evaluation of the increasingly popular class of limited-energy LIDARs using the best optical detectors, operating on different targets (back-scatter or topographic, static or dynamic) and under intense sky background conditions. It can be used in the LIDAR community to compare different instruments and select the most suitable and effective ones for specific applications. PMID- 29791334 TI - Improved force prediction model for grinding Zerodur based on the comprehensive material removal mechanism. AB - There have been few investigations dealing with the force model on grinding brittle materials. However, the dynamic material removal mechanisms have not yet been sufficiently explicated through the grain-workpiece interaction statuses while considering the brittle material characteristics. This paper proposes an improved grinding force model for Zerodur, which contains ductile removal force, brittle removal force, and frictional force, corresponding to the ductile and brittle material removal phases, as well as the friction process, respectively. The critical uncut chip thickness agc of brittle-ductile transition and the maximum uncut chip thickness agmax of a single abrasive grain are calculated to identify the specified material removal mode, while the comparative result between agmax and agc can be applied to determine the selection of effective grinding force components. Subsequently, indentation fracture tests are carried out to acquire accurate material mechanical properties of Zerodur in establishing the brittle removal force model. Then, the experiments were conducted to derive the coefficients in the grinding force prediction model. Simulated through this model, correlations between the grinding force and grinding parameters can be predicted. Finally, three groups of grinding experiments are carried out to validate the mathematical grinding force model. The experimental results indicate that the improved model is capable of predicting the realistic grinding force accurately with the relative mean errors of 6.04% to the normal grinding force and 7.22% to the tangential grinding force, respectively. PMID- 29791335 TI - Paraxial design of an optical element with variable focal length and fixed position of principal planes. AB - In this article, we analyze the problem of the paraxial design of an active optical element with variable focal length, which maintains the positions of its principal planes fixed during the change of its optical power. Such optical elements are important in the process of design of complex optical systems (e.g., zoom systems), where the fixed position of principal planes during the change of optical power is essential for the design process. The proposed solution is based on the generalized membrane tunable-focus fluidic lens with several membrane surfaces. PMID- 29791336 TI - Optimization of optical properties of photonic crystal fibers infiltrated with carbon tetrachloride for supercontinuum generation with subnanojoule femtosecond pulses. AB - A photonic crystal fiber (PCF) made of fused silica glass, infiltrated with carbon tetrachloride (CCl4), is proposed as a new source of supercontinuum (SC) light. Guiding properties in terms of effective refractive index, attenuation, and dispersion of the fundamental mode are studied numerically. As a result, two optimized structures are selected and verified against SC generation in detail. The dispersion characteristic of the first structure has the zero-dispersion wavelength at 1.252 MUm, while the dispersion characteristic of the second structure is all-normal and equals -4.37 ps.nm-1.km-1 at 1.55 MUm. SC generation was demonstrated for the wavelengths 1.064 MUm, 1.35 MUm, and 1.55 MUm. We prove the possibility of coherent, octave-spanning SC generation with 300 fs pulses with only 0.8 nJ of energy in-coupled into the core with each of the studied structures. Proposed fibers are fully compatible with all-silica fiber systems and PCFs with wide mode area, and can also be used for all-fiber SC sources. The proposed solution may lead to new low-cost all-fiber optical systems. PMID- 29791337 TI - Applicability of a model with average inversion level to a cladding-pumped multicore erbium-doped fiber amplifier. AB - This paper investigates the applicability of a model of a cladding-pumped multicore erbium-doped fiber amplifier (CP-MC-EDFA) that employs the average inversion level of an erbium ion. The model is modified to include the effects of multiple cores for modifications of the background loss coefficient of the pump light. The model is validated experimentally by measurements of the pump power, gain transient, and intercore cross-gain modulation of a cladding-pumped 12-core EDFA in which the pump light is uniformly distributed in the inner cladding. The calculated and measured pump power, gain transient response, and gain change caused by the intercore cross-gain modulation agree well, suggesting the modified model is useful for characterizing a CP-MC-EDFA. PMID- 29791338 TI - Imaging photonic crystals using hemispherical digital condensers and phase recovery techniques. AB - We describe experiments where Fourier ptychographic microscopy (FPM) and dual space microscopy (DSM) are implemented for imaging photonic crystals using a hemispherical digital condenser (HDC). Phase-recovery imaging simulations show that both techniques should be able to image photonic crystals with a period below the Rayleigh resolution limit. However, after processing the experimental images using both phase-recovery algorithms, we found that DSM can, but FPM cannot, image periodic structures with a period below the diffraction limit. We studied the origin of this apparent contradiction between simulations and experiments, and we concluded that the occurrence of unwanted reflections in the HDC is the source of the apparent failure of FPM. We thereafter solved the problem of reflections by using a single-directional illumination source and showed that FPM can image photonic crystals with a period below the Rayleigh resolution limit. PMID- 29791339 TI - Rapid measurement and compensation method of eccentricity in automatic profile measurement of the ICF capsule. AB - In this paper, we propose a new measurement and compensation method for the eccentricity of the inertial confinement fusion (ICF) capsule, which combines computer vision and the laser differential confocal method to align the capsule in rotation measurement. This technique measures the eccentricity of the capsule by obtaining the sub-pixel profile with a moment-based algorithm, then performs the preliminary alignment by the two-dimensional adjustment. Next, we use the laser differential confocal sensor to measure the height data of the equatorial surface of the capsule by turning it around, then obtain and compensate the remaining eccentricity ultimately. This method is a non-contact, automatic, rapid, high-precision measurement and compensation technique of eccentricity for the capsule. Theoretical analyses and preliminary experiments indicate that the maximum measurement range of eccentricity of this proposed method is 1.8 mm for the capsule with a diameter of 1 mm, and it could eliminate the eccentricity to less than 0.5 MUm in 30 s. PMID- 29791340 TI - Design of a delayed XOR phase detector for an optical phase-locked loop toward high-speed coherent laser communication. AB - Optical phase-locked loops are an effective detection method in high-speed and long-distance laser communication. Although this method can detect weak signal light and maintain a small bit error rate, it is difficult to perform because identifying the phase difference between the signal light and the local oscillator accurately has always been a technical challenge. Thus, a series of studies is conducted to address this issue. First, a delayed exclusive or gate (XOR) phase detector with multi-level loop compound control is proposed. Then, a 50 ps delay line and relative signal-to-noise ratio control at 15 dB are produced through theoretical derivation and simulation. Thereafter, a phase discrimination module is designed on a 15 cm*5 cm printed circuit board board. Finally, the experiment platform is built for verification. Experimental results show that the phase discrimination range is -1.1 to 1.1 GHz, and the gain is 0.82 mV/MHz. Three times the standard deviation, that is, 0.064 V, is observed between the test and theoretical values. The accuracy of phase detection is better than 0.07 V, which meets the design standards. A coherent carrier recovery test system is established. The delayed XOR gate has good performance in this system. When the communication rate is 5 Gbps, the system realizes a bit error rate of 1.55*10-8 when the optical power of the signal is -40.4 dBm. When the communication rate is increased to 10 Gbps, the detection sensitivity drops to -39.5 dBm and still shows good performance in high-speed communications. This work provides a reference for future high-speed coherent homodyne detection in space. Ideas for the next phase of this study are presented at the end of this paper. PMID- 29791341 TI - Fabrication of a silica-based complex Fourier-transform integrated-optic spatial heterodyne spectrometer incorporating 120 degrees optical hybrid couplers. AB - We demonstrate a silica-based planar waveguide spatial heterodyne spectrometer incorporating 120 degrees optical hybrid 3*3 MMI couplers as the output couplers in 32 MZIs, which enabled us to derive the spectrum without use of the previously reported dynamic phase shifting. The free spectral range was 640 GHz, and the spectral resolution was 14 GHz. We used a CO2 laser irradiation method to calibrate the light powers from all the output ports of the couplers and to measure the optical phases and amplitudes at the individual MZIs. We solved the resultant system of three linear equations at each MZI and performed a complex Fourier transformation to derive a narrowband light spectrum. The background noise level of the retrieved spectrum was 0.05 with respect to the peak even when no window function was applied. PMID- 29791342 TI - Solution of dispersion relations of multilayer optical fibers: a comprehensive study. AB - The exact solution of the modal dispersion relation of multilayer optical fibers is very critical and complicated, especially in the case of complex refractive indices of some layers added to the fiber. In this paper, a different methodology is proposed to solve the complex dispersion relations for cladding modes, based on the well-defined proper expressions of electromagnetic fields in the different layers of optical fibers. An optical fiber, coated by a dielectric nonlinear layer, is analyzed using the exact four-layer model, and the results obtained are compared with those analyzed in the literature based on the approximate three layer model, where the effect of the coating layer is neglected when solving the dispersion relation. The results obtained show a remarkable difference between the exact and the approximate values of the effective refractive indices of the cladding modes. Inappropriate values of the effective refractive indices strongly affect phase matching and coupling between modes, which are required in different applications such as second-harmonic generation. The proposed approach for solving general dispersion relations is also employed to obtain complex values of the effective refractive indices of the cladding modes for a five-layer optical fiber with a metallic thin film inserted between the nonlinear layer and the fiber cladding. Using the appropriate expressions that describe the electric field in the different dielectric and metallic layers of optical fibers, field distributions are displayed for some cladding modes. PMID- 29791343 TI - Research on a surface-relief optical waveguide augmented reality display device. AB - Recently, an optical waveguide display device that has light weight, high transparency, and full color has become more and more popular in the wearable augmented reality display application. But existing waveguide display devices are less than satisfactory because of cost, safety, and mass production. Therefore, a type of surface-relief optical waveguide display device is proposed in this paper. First, the geometrical relationship of a waveguide display device structure is confirmed according to the design method of the optical waveguide display device. Then, the influence of the waveguide structure for the image quality is analyzed, and the rationality of the surface-relief waveguide scheme is verified by simulation. Finally, the prototype of the surface-relief optical waveguide display device with polycarbonate materials, field of view of 38 degrees , thickness of 4.5 mm, and transmittance of about 80% is fabricated and demonstrated. PMID- 29791344 TI - Analytical-performance improvement of laser-induced breakdown spectroscopy for the processing degree of wheat flour using a continuous wavelet transform. AB - Quality and safety of food are two of the most important matters in our lives. Wheat is one of the most important products in the modern agricultural processing industry. Issues of mislabeling and adulteration are of increasingly serious concern in the grain market. They threaten the credibility of producers and traders and the rights of the consumers. Therefore, it is very significant to guarantee the processing degree of wheat flour. In this work, two different spectral peak recognition methods, i.e., artificial spectral peak recognition and automatic spectral peak recognition, are carried out to study the adulteration problem in the food industry. Three grades of the processing degree of wheat flour from northern China are classified by laser-induced breakdown spectroscopy (LIBS). To search for an automatic classification model, continuous wavelet transform is used for the automatic recognition of the LIBS spectrum peak. Principal component analysis is used to reduce the collinearity of LIBS spectra data. First, 20 principal components were selected to represent the spectral data for the following discrimination analysis by a support vector machine. The results showed that the classification accuracies of automatic spectral peak recognition are better than those of artificial spectral peak recognition. The classification accuracies of artificial spectral peak recognition and automatic spectral peak recognition are 95.33% and 98.67%; the fivefold cross-validation classification accuracies are 94.67% and 96.67%; and the operation times were 240 min and 2 min, respectively. It can be concluded that LIBS can provide simpler and faster classification without the use of any chemical reagent, which represents a decisive advantage for applications dedicated to rapidly detecting the processing degree of wheat flour and other cereals. PMID- 29791345 TI - Piezo-, elasto- and acousto-optic properties of Tl3AsS4 crystals. AB - Complete matrices of piezo-optic and elasto-optic tensors are experimentally determined for Tl3AsS4 crystals. It is revealed that the piezo-optic coefficients are very high, ~10-11 N/m2 in the order of magnitude. This implies that Tl3AsS4 can be referred to the best piezo-optic materials. The same concerns the elasto optic coefficients, of which absolute values are in the interval 0.28-0.54. It is also found that, at the anisotropic and isotropic interactions with the slowest transverse and longitudinal acoustic waves, the acousto-optic figure of merit reaches extremely high values (1.99*10-12 s3/kg and 9.45*10-13 s3/kg, respectively). In other words, the Tl3AsS4 crystals can be referred to as one of the best acousto-optic materials for the visible and infrared spectral ranges. PMID- 29791346 TI - Characterization of the focusing performance of axial line-focused spiral zone plates. AB - Axial line-focused spiral zone plates were developed for operation at optical wavelengths. The design, fabrication, and diffraction properties of the proposed element are presented. Numerical results showed that hollow beams could be generated, and that the element can be employed for a multi-wavelength operation. The hollow beam within the focal depth was demonstrated experimentally, using a charge-coupled device camera and sliding guide. The results were consistent with those obtained by the simulations. The proposed optical device exhibits significant potential for various applications including optical manipulation and lithography. PMID- 29791347 TI - Freeform characterization based on nanostructured diffraction gratings. AB - The in-line characterization of freeform optical elements during the production cycle is challenging. Recently, we presented a compact sensor setup for the characterization of the wavefront generated by freeform optical elements in transmission. The sensor is based on a common-path interferometer consisting of diffractive components and Fourier filtering being adapted to the subsequent numerical post processing. Additionally, it offers several degrees of freedom for enlarging the measurement range of the wavefront gradients. In this contribution, we propose an advanced sensor setup for the measurement of wavefronts generated by freeform elements in reflection. The main advantage is the uni-axial illumination of the test object and the measuring system without the need for conventional beamsplitters. Due to this uni-axial arrangement, the main challenge is to avoid the effect of stray light and back reflections on the measurement signal-to-noise ratio. This is achieved by implementing a highly absorbing amplitude grating based on nanostructured silicon. We demonstrate the experimentally realized measurement system and compare its performance to a commercial Shack-Hartmann sensor. PMID- 29791348 TI - Detection of iron atoms by emission spectroscopy and laser-induced fluorescence in solid propellant flames. AB - Planar laser-induced fluorescence on atomic iron is investigated in this paper, and a measurement strategy is proposed to monitor the fluorescence of iron atoms with good sensitivity. A model is proposed to fit the experimental fluorescence spectra, and good agreement is found between simulated and experimental spectra. Emission and laser-induced fluorescence measurements are performed in the flames of ammonium perchlorate composite propellants containing iron-based catalysts. A fluorescence signal from iron atoms after excitation at 248 nm is observed for the first time in propellant flames. Images of the spatial distribution of iron atoms are recorded in the flame in which turbulent structures are generated. Iron fluorescence is detected up to 1.0 MPa, which opens the way to application in propellant combustion. PMID- 29791349 TI - Polarimetric learning: a Siamese approach to learning distance metrics of algal Mueller matrix images. AB - Polarimetric measurements are becoming increasingly accurate and fast to perform in modern applications. However, analysis on the polarimetric data usually suffers from its high-dimensional nature spatially, temporally, or spectrally. This paper associates polarimetric techniques with metric learning algorithms, namely, polarimetric learning, by introducing a distance metric learning method called Siamese network that aims to learn good distance metrics of algal Mueller matrix images in low-dimensional feature spaces. As an experimental example, 12,162 Mueller matrix images of eight algal species are measured via a forward Mueller matrix microscope. Eight classical metric learning algorithms, including principle component analysis, multidimensional scaling, isometric feature mapping, t-distributed stochastic neighbor embedding, Laplacian eigenmaps, locally linear embedding, linear discriminant analysis, and metric learning to rank, are considered, by which the algal Mueller matrix images are mapped to two dimensional (2D) feature spaces with different distance metrics. Support-vector machine-based holdout sample classification accuracies of the 2D feature vectors are provided in a supervised manner for quantitative comparisons of the low dimensional distance metrics, including the results of the eight metric learning algorithms and 16 Siamese architectures with varying convolution, inception, and full connection modules. This study shows that the Siamese approach is an effective metric learning algorithm that can adaptively extract features exhibiting empirical correlations with the fast-axis-orientation-dependent and spatially variant algal retardance induced by the algal microstructures. PMID- 29791350 TI - Compact InGaAsP/InP nonblocking 4 * 4 trench-coupler-based Mach-Zehnder photonic switch fabric. AB - The existing photonic switch matrices usually show the drawbacks of either a large footprint or high cross talk. Here, we propose a compact InGaAsP/InP rearrangeable nonblocking 4*4 photonic switch fabric based on 2*2 Mach-Zehnder interferometer (MZI) switch elements in a Benes architecture. Each switch element consists of two frustrated total internal reflection (TIR) couplers and TIR mirrors serving as 90 degrees waveguide bends, forming the square layout configuration of the 2*2 MZI switches. We investigate the design parameters of the switch element and 4*4 photonic switch matrix by using FDTD and transfer matrix methods, respectively. Our analysis results show that the proposed device exhibits an ultracompact chip size of ~340 MUm*120 MUm, the minimum cross talk of -23 dB in the 1.5~1.6 MUm wavelength range, the total insertion loss of ~3.9 dB, the low electrical energy of ~0.4 pJ/bit, and an operation speed up to 50 GHz. Experimentally, we can demonstrate the feasibility of fabricating 2*2 MZI switches and an operational low-loss trench-coupler. The enabling component of the 2*2 MZI switch can scale its pattern in the 2D directions. This as-formed compact 4*4 switch fabric can be potentially applied in large-scale InP-based photonic integrated circuits. PMID- 29791351 TI - Ultrashort polarization beam splitter based on liquid-filled dual-core photonic crystal fiber. AB - An ultrashort polarization beam splitter (PBS) is proposed based on liquid-filled dual-core photonic crystal fiber (DCPCF). The two cores of DCPCF are formed by two side elliptical holes and a central circular hole in the horizontal direction. The properties of the PBS are analyzed first with a non-filled DCPCF by the finite element method. Then, the performances of the PBS are discussed when the DCPCF is filled with liquids in the central hole. As a result, an ultrashort PBS is realized with a length of 78 MUm when glycerol solution with a concentration of 37% is filled in the central hole. In this case, an extinction ratio of 87 dB is obtained at 1550 nm wavelength. The significantly short device shows a great advantage when being integrated in ultra-compact optical systems. PMID- 29791352 TI - Analyzing characteristics of spiral vector beams generated by mixing of orthogonal LP11 modes in a few-mode optical fiber. AB - We have demonstrated a method for the generation of spiral vector beams using a few-mode optical fiber. The beams are generated due to the combination of orthogonal linearly polarized modes with a tilted polarization vector in the few mode optical fiber. The excitation of these modes is controlled by the incident state of polarization and coupling conditions at the input end of the fiber. The beams with clockwise and counterclockwise nature of spiral polarization are generated, and switching between them is demonstrated. The obtained results emphasize the strong dependency of polarization of generated spiral vector beams and other orthogonal linearly polarized modes on the input state of polarization. The simulated results of mode mixing are verified experimentally with good agreement. PMID- 29791353 TI - Deep-learning-generated holography. AB - We present a method for computer-generated holography based on deep learning. The inverse process of light propagation is regressed with a number of computationally generated speckle data sets. This method enables noniterative calculation of computer-generated holograms (CGHs). The proposed method was experimentally verified with a phase-only CGH. PMID- 29791354 TI - Improved three-dimensional reconstruction algorithm from a multifocus microscopic image sequence based on a nonsubsampled wavelet transform. AB - In the multifocus microscopic image measurement method, the distortion of the three-dimensional (3D) reconstruction model has always been an important factor affecting the measurement result. In spatial domains, the focus measure algorithm is based on the gradient change of the pixel point to determine the degree of focus of the pixel. So it will be difficult to accurately extract the focus of the pixel in the areas where color difference is not obvious, resulting in 3D model distortion. According to the optical principle, the high-frequency coefficients of the clear image are larger than the high-frequency coefficients of the blurred image. Based on this characteristic, this paper proposes a new multifocus microscopic image 3D reconstruction algorithm using a nonsubsampled wavelet transform (NSWT). The NSWT does not consider the downsampling in wavelet decomposition and has translational invariance. Therefore, the wavelet transform value of each pixel can be calculated in the image, so the high-frequency coefficient of each pixel can be obtained; then the convolution calculation is performed on the high-frequency coefficients of the pixel points in the fixed window as the focus measure value of the pixel point. Compared with the traditional algorithm, the algorithm proposed in this paper can show better unimodal and antinoise performance on the focusing measure curve. In this paper, the reconstruction of the experimental object is Alicona standard block triangular and semicylindrical. The proposed algorithm and the traditional algorithm for comprehensive measure use the root mean square error, peak signal to noise ratio, and correlation coefficient as the measure index. The experimental results and comparative analysis prove the correctness of the proposed algorithm and enable more accurate reconstruction of 3D models based on multifocus microscopic images. PMID- 29791355 TI - Laser coarse-fine coupling tracking by cascaded rotation Risley-prism pairs. AB - Rotation Risley prisms are increasingly used for laser tracking due to high precision and good dynamic performance. In this paper, a novel laser coarse-fine coupling tracking method based on two pairs of rotation Risley prisms is proposed to perform the forward and inverse tracking function. The second pair of rotation Risley prisms with narrower wedge angle can achieve higher precision tracking with narrower field of view than the first one, enriching the coarse-fine coupling tracking trajectory patterns. Moreover, an inverse algorithm based on the two-step method and Newton's iterative method is applied to solve the inverse issue for laser coarse-fine coupling tracking. Two cases further demonstrate that the motion switching strategy executed with the inverse solutions can steer the beam to track the desired motion trajectory. An experiment validates the availability of the cascaded rotation Risley-prism pairs to perform the laser coarse-fine coupling tracking function. PMID- 29791356 TI - Linewidth in saturated absorption spectroscopy for two-level atoms: an empirical formula. AB - We present an empirical formula for linewidth in saturated absorption spectroscopy for two-level atoms with cycling transition lines, taking the coherence term in the Doppler-broadened limit into account. The full width at half-maximum is obtained as (1+(1+as0)b)gammat, where s0 is the on-resonance saturation parameter, gammat is the transverse decay rate, and a and b are the parameters that depend on gammat. We find that as gammat increases, a and b approach 1 and 1/2, respectively. These are the typical values in the case without the coherence term. PMID- 29791357 TI - Synthetic model of nonlinearity errors in laser heterodyne interferometry. AB - The development of laser heterodyne interferometry raises the requirements of measurement resolution and accuracy. However, periodic nonlinearity errors mainly suppress the accuracy of laser heterodyne interferometry. Based on the generation mechanism of nonlinearity errors, the sources of nonlinearity errors in laser heterodyne interferometry are first analyzed in this paper. Then, a synthetic model is established to analyze the influences of various nonlinearity error sources on the first- and second-harmonic nonlinearity errors. The first-harmonic nonlinearity errors can be reduced and suppressed by adjusting the orientation error of optical elements in a heterodyne interferometer. Furthermore, the azimuthal misalignment of the polarization beam splitter (PBS) is the main source of the second-harmonic nonlinearity errors. Therefore, when in heterodyne interferometer, the azimuthal misalignment of the PBS should be avoided if possible. This study provides theoretical basis for reducing and compensating nonlinearity errors in a laser heterodyne interferometer. PMID- 29791358 TI - Partial saturation-aided resolution enhancement for digital holography. AB - Because of the limited dynamic range of common detectors, high-frequency components weaker than the threshold of the detector used are lost in digital holography (DH) even with the aid of coherent diffraction imaging (CDI)-based iterative computation, and this makes DH less preferable for many interesting applications. To overcome this problem, the partially saturated diffraction pattern was adopted to enhance the resolution of DH iteratively. Since more high frequency components were retrieved in comparison with our former CDI-based digital holographic method, the resolution of DH was improved further. The feasibility of the proposed method is demonstrated both numerically and experimentally. PMID- 29791359 TI - Efficient high power, narrow linewidth 1.9 MUm fiber hydrogen Raman amplifier. AB - We report here an efficient, high power, narrow linewidth 1.9 MUm gas Raman amplifier by means of a hydrogen-filled hollow-core fiber. A 1.9 MUm narrow linewidth continuous wave seed laser is coupled into the hollow-core fiber together with a high power pulsed 1064 nm MOPA laser through a shortpass dichroic mirror, and then amplified by stimulated Raman scattering of hydrogen. With 2 m fiber length and 4.5 bar gas pressure, the maximum average 1908 nm Stokes power of 570 mW is obtained, a record average power level for such experiments. The maximum peak power is about 50 kW, the linewidth is about 1 GHz, and the quantum efficiency is about 51%. This work has demonstrated the potential to get a high average power gas Raman laser in a hollow-core fiber, and it further provides the possibility to achieve a high average power 4 MUm midinfrared fiber laser by cascaded gas stimulated Raman scattering. PMID- 29791360 TI - High-speed focal-distance-modulated fiber-coupled confocal sensor for coordinate measuring systems. AB - This article presents a new robust, precise, high-frequency focal-distance modulated confocal point sensor for probing in coordinate measuring systems (CMSs). While maintaining the known advantages of the confocal measurement principle, the sensor represents an innovative combination of a fiber-coupled confocal illumination and detection with a tuneable, acoustically driven gradient index fluid lens for modulation of the focus distance and a novel signal processing utilizing a lock-in amplifier. The new arrangement is able to achieve an approximately linear characteristic curve for the optimized feedback control of the CMS in scanning sample mode. This article emphasizes the optical application and the signal processing of the setup. PMID- 29791361 TI - No-reference stereoscopic image quality assessment based on hue summation difference mapping image and binocular joint mutual filtering. AB - The no-reference (NR) quality assessment for stereoscopic images plays a significant role in 3D technology, but it also faces great challenges. In this paper, a novel NR stereo image quality assessment (SIQA) method is proposed. Based on the human visual system, this method mimics the summation and difference channels, which consider the binocular interactive perception property, to process the visual information. Especially, the summation and difference images are calculated by the contrast of hue and luminance in color patches. Meanwhile, considering the interactive filtering between the left and right viewpoints, this method uses the filtered information as the weighting factor to integrate the visual information of the summation and difference channels to form the summation difference mapping image (SDMI). Then, energy entropy, bivariate generalized Gaussian distribution for the joint distribution of SDMI and the depth map subband coefficients, and the local log-Euclidean multivariate Gaussian descriptor are detected as the feature descriptors. Support vector regression, trained by the features, is utilized to predict the quality of stereoscopic images. Experimental results demonstrate that the proposed algorithm achieves high consistency with subjective assessment on four SIQA databases. PMID- 29791362 TI - Real-time super-resolved 3D in turbid water using a fast range-gated CMOS camera. AB - We present a range-gated camera system designed for real-time (10 Hz) 3D estimation underwater. The system uses a fast-shutter CMOS sensor (1280*1024) customized to facilitate gating with 1.67 ns (18.8 cm in water) delay steps relative to the triggering of a solid-state actively Q-switched 532 nm laser. A depth estimation algorithm has been carefully designed to handle the effects of light scattering in water, i.e., forward and backward scattering. The raw range gated signal is carefully filtered to reduce noise while preserving the signal even in the presence of unwanted backscatter. The resulting signal is proportional to the number of photons that are reflected during a small time unit (range), and objects will show up as peaks in the filtered signal. We present a peak-finding algorithm that is robust to unwanted forward scatter peaks and at the same time can pick out distant peaks that are barely higher than peaks caused by sensor and intensity noise. Super-resolution is achieved by fitting a parabola around the peak, which we show can provide depth precision below 1 cm at high signal levels. We show depth estimation results when scanning a range of 8 m (typically 1-9 m) at 10 Hz. The results are dependent on the water quality. We are capable of estimating depth at distances of over 4.5 attenuation lengths when imaging high albedo targets at low attenuation lengths, and we achieve a depth resolution (sigma) ranging from 0.8 to 9 cm, depending on signal level. PMID- 29791363 TI - Design of a portable phantom device to simulate tissue oxygenation and blood perfusion. AB - We propose a portable phantom system for calibration and validation of medical optical devices in a clinical setting. The phantom system comprises a perfusion module and an exchangeable tissue-simulating phantom that simulates tissue oxygenation and blood perfusion. The perfusion module consists of a peristaltic pump, two liquid storage units, and two pressure suppressors. The tissue simulating phantom is fabricated by a three-dimensional (3D) printing process with microchannels embedded to simulate blood vessels. Optical scattering and absorption properties of biologic tissue are simulated by mixing graphite powder and titanium dioxide powder with clear photoreactive resin at specific ratios. Tissue oxygen saturation (StO2) and blood perfusion are simulated by circulating the mixture of blood and intralipid at different oxygenation levels and flow rates. A house-made multimodal imaging system that combines multispectral imaging and laser speckle imaging are used for non-invasive detection of phantom oxygenation and perfusion, and the measurements are compared with those of a commercial Moor device as well as numerical simulation. By acquiring multimodal imaging data from one phantom and applying the calibration factors in different settings, we demonstrate the technical feasibility to calibrate optical devices for consistent measurements. By simulating retina tissue vasculature and acquiring functional images at different tissue oxygenation and blood perfusion levels, we demonstrate the clinical potential to simulate tissue anomalies. Our experiments imply the clinical potential of a portable, low-cost, and traceable phantom standard to calibrate and validate medical optical devices for improved performance. PMID- 29791364 TI - Synchronization of pairs of nanosecond pulses from a laser with two gain crystals pumped with two different sources. AB - We report a laser that emits two Q-switched pulses, one at 1.047 MUm and the other at 1.064 MUm, generated by a Nd:YLF and a Nd:YVO4, respectively. The crystals are pumped by two fiber-coupled diode lasers (808 nm and 880 nm); the delay between the pulses can be controlled by adjusting the power of the pumps. Two kinds of Q-switching techniques are reported, passive (Cr:YAG saturable absorber) and active (electro-optic modulator). We model both the active and passive Q switching and make a comparison between numerical simulations and experiments. We show experimentally and theoretically that in both cases the pulses can be synchronized; however, the stability of the synchronization (sensitivity to pump power fluctuations) is better for active than for passive Q switching. We also report that under certain experimental conditions a third wavelength is obtained, 1156 nm, which corresponds to the first Stokes shift of the 1047 nm pulse produced by stimulated Raman scattering from the Nd:YVO4 crystal. PMID- 29791365 TI - 3D-printed polymer antiresonant waveguides for short-reach terahertz applications. AB - In this work, we present a 3D-printed waveguide that provides effective electromagnetic guidance in the THz regime. The waveguide is printed using low cost polycarbonate and a conventional fused deposition modeling printer. Light guidance in the hollow core is achieved through antiresonance, and it improves the energy effectively transported to the receiver compared to free space propagation. Our demonstration adds to the field of 3D-printed terahertz components, providing a low-cost way of guiding terahertz radiation. PMID- 29791366 TI - Optimization of all-dielectric structures for color generation. AB - In this work, we propose an inversion scheme to tailor the chromatic response of an all-dielectric structure. To this end, we couple, through a previously defined objective functional involving the concept of color difference, a forward solver with an optimization algorithm. The former is based on the differential method, whereas the latter is based on particle swarm optimization. The optimal geometrical parameters of the structure that generates a specific color are obtained through the solution of an approximation problem. We illustrate the performance of our inversion scheme through examples and discuss its limitations and potential applications. PMID- 29791367 TI - Improved space object detection using short-exposure image data with daylight background. AB - Space object detection is of great importance in the highly dependent yet competitive and congested space domain. The detection algorithms employed play a crucial role in fulfilling the detection component in the space situational awareness mission to detect, track, characterize, and catalog unknown space objects. Many current space detection algorithms use a matched filter or a spatial correlator on long-exposure data to make a detection decision at a single pixel point of a spatial image based on the assumption that the data follow a Gaussian distribution. Long-exposure imaging is critical to detection performance in these algorithms; however, for imaging under daylight conditions, it becomes necessary to create a long-exposure image as the sum of many short-exposure images. This paper explores the potential for increasing detection capabilities for small and dim space objects in a stack of short-exposure images dominated by a bright background. The algorithm proposed in this paper improves the traditional stack and average method of forming a long-exposure image by selectively removing short-exposure frames of data that do not positively contribute to the overall signal-to-noise ratio of the averaged image. The performance of the algorithm is compared to a traditional matched filter detector using data generated in MATLAB as well as laboratory-collected data. The results are illustrated on a receiver operating characteristic curve to highlight the increased probability of detection associated with the proposed algorithm. PMID- 29791368 TI - Design and analysis for a bend-resistant and large-mode-area photonic crystal fiber with hybrid cladding. AB - In this paper, an asymmetric large-mode-area photonic crystal fiber (LMA-PCF) with low bending loss at a smaller bending radius is designed. The finite-element method with a perfectly matched layer boundary is used to analyze the performance of the PCF. To achieve LMA-PCF with low bending loss, the air holes with double lattice constants and different sizes at the core are designed. Numerical results show that this structure can achieve low bending loss and LMA with a smaller bending radius at the wavelength of 1.55 MUm. The effective mode area of the fundamental mode is larger than 1000 MUm2 when the bending radius is >=10 cm. The bending loss of the fundamental mode is just 0.0113 dB/m, and the difference between the fundamental and high-order modes of the bending loss is larger than 103 when the bending radius is 10 cm. Simulation results show this novel PCF can achieve LMA and have effective single-mode operation when the bending orientation angle ranges in +/-110 degrees . This novel photonic crystal has potential application in high-power fiber lasers. PMID- 29791369 TI - Three-dimensional shape measurement using a structured light system with dual projectors. AB - This paper introduces a structured light system with two projectors and one camera for three-dimensional (3D) shape measurement to alleviate problems created by a single projector such as the shadow problem. In particular, we developed (1) a system calibration framework that can accurately calibrate each such camera projector system; (2) a residual error correction method based on the system error function; and (3) a data fusion method utilizing the angle between the projection direction and surface normal. Experimental results demonstrate that the proposed dual-projector structured light system improves the measurement accuracy besides extending the measurement range of a single projector system. PMID- 29791370 TI - Band optimization of passive methane gas leak detection based on uncooled infrared focal plane array. AB - Current methane gas leak detection technology uses infrared imaging in the medium wave (MW) or long wave (LW) bands, essentially applying cooled infrared detectors. In this study, a simplified three-layer radiative transfer model is adopted based on methane gas detection theory, considering background radiation, atmospheric infrared absorption, gas absorption, and emission characteristics to analyze the contrast of methane gas thermography in different infrared bands. The analysis results suggest that under certain conditions, the 6.6-8.6 MUm LW band provides higher contrast compared to the 3-5 MUm MW band. The optimal imaging wavelength band is selected according to imaging contrast advantages and disadvantages, and infrared optical systems and infrared filters are designed and optimized. We build a passive methane gas leak detection system based on uncooled infrared focal plane array detectors. By collecting gas images under different conditions, the imaging detection capabilities for methane gas leaks in the MW and LW bands in a laboratory environment are compared. Finally, the developing trends in methane gas detection technology are analyzed. PMID- 29791371 TI - Ultrahigh sensitivity refractive index sensor of a D-shaped PCF based on surface plasmon resonance. AB - We propose a D-shaped photonic crystal fiber (PCF) refractive index sensor with ultrahigh sensitivity and a wide detection range. The gold layer is deposited on the polished surface, avoiding filling or coating inside the air holes of the PCF. The influences of the gold layer thickness and the diameter of the larger air holes are investigated. The sensing characteristics of the proposed sensor are analyzed by the finite element method. The maximum sensitivity can reach 31,000 nm/RIU, and the refractive index detection range is from 1.32 to 1.40. Our proposed PCF has excellent sensing characteristics and is competitive in sensing devices. PMID- 29791372 TI - Theoretical compensation of static deformations of freeform multimirror substrates. AB - Varying temperatures influence the figure errors of freeform metal mirrors by thermal expansion. Furthermore, different materials lead to thermo-elastic bending effects. The paper presents a derivation of a compensation approach for general static loads. Utilizing perturbation theory, this approach works for shape compensation of substrates that operate in various temperature environments. Verification is made using a finite element analysis, which is further used to produce manufacturable CAD models. The remaining low spatial frequency errors are deterministically correctable using diamond turning or polishing techniques. PMID- 29791373 TI - Broadband TE-pass slot waveguide polarizer using an asymmetrical directional coupler. AB - A compact TE-pass polarizer for silicon-based slot waveguides is numerically proposed based on a directional coupler where an asymmetrical slot waveguide (ASW) and hybrid plasmonic waveguide (HPW) are involved. The input section is linearly tapered to an ASW to markedly enlarge the modal birefringence. Beneficially, only the TM mode can be coupled into the adjacent HPW and attenuated while the injected TE mode just passes through the slot waveguide without coupling by properly choosing the dimensions. As a consequence, an efficient TE-pass polarizer can be implemented. From the simulation results, the proposed polarizer has an extinction ratio (ER) of 45 dB and insertion loss (IL) of 0.44 dB at 1.55 MUm, and its bandwidth exceeds 130 nm with the ER>30 dB and IL<1 dB. In addition, fabrication tolerances to the key structural parameters are analyzed and field evolution along the propagation distance is also demonstrated. PMID- 29791374 TI - Enhancement of Goos-Hanchen shift due to a Rydberg state. AB - This paper hints at the Goos-Hanchen shift properties of a cavity containing an ensemble of atoms using a four-level atomic system involving a Rydberg state. By means of the stationary phase theory and density matrix formalism in quantum optics, we study theoretically the Goos-Hanchen shifts in both reflected and transmitted light beams. It is realized that as a result of the interaction between Rydberg and excited states in such a four-level atom-light coupling scheme the maximum positive and negative Goos-Hanchen shifts can be obtained in reflected and transmitted light beams owning to the effect of the Rydberg electromagnetically induced transparency (EIT) or Rydberg electromagnetically induced absorption. In particular, when the switching field is absent and the Rydberg EIT is dominant in the medium, a giant Goos-Hanchen shift can be achieved for both reflected and transmitted light beams. PMID- 29791375 TI - Tunable double-mode sensor for multi-gas detection based on the external-cavity diode laser. AB - An optoelectronic sensor system based on a thermoelectrically cooled (TEC) continuous-wave (CW) double-mode external-cavity diode laser (ECDL) is demonstrated for a multi-gas analysis in this paper. An ECDL that can simultaneously emit at two different wavelengths in the range from 1275 to 1340 nm was utilized as the excitation source for molecule absorption. Each wavelength can be independently tuned. The ECDL was combined with an off-axis cavity enhanced absorption spectroscopy (OA-CEAS) cell to perform multi-gas sensing. It was shown that the sensor system can be used for detection of multiple trace gases (H2O, CO2, and CH4). The advantages of the reported sensor system are that a single laser and detector system are utilized and that there is no overlapping between the two modes on the mirror surfaces because of the single fiber output from the ECDL. PMID- 29791376 TI - TM01 mode in a cylindrical hybrid plasmonic waveguide with large propagation length. AB - This study reports on a cylindrical hybrid plasmonic waveguide (CHPW) consisting of a high-index dielectric core, a sandwiched low-index dielectric layer, and a metal cladding. The CHPW supports the TM01 mode with a radially polarized transverse component of the electric field. Optical fields can be significantly enhanced in the sandwiched low-index dielectric region with nanoscale thickness down to 5 nm, and tight mode confinement with the same order of the normalized mode area compared with that of the plasmonic waveguide is achieved. Moreover, the mode propagation loss is well compensated by adjusting dimensions of the waveguide to obtain a longer propagation distance. The calculated figure of merit reaches a value several times greater than that in the similarly reported structure. The results indicate that this novel type of hybrid structure can support the limited propagation of a radially polarized mode with good confinement and low loss, consummate the whole system of manipulating the cylindrical vector beams, and show great potential of applications for various integrated nano-photonic devices. PMID- 29791377 TI - 27.5 W/m2 collection efficiency solar laser using a diffuse scattering cooling liquid. AB - We report a solar pumped solid state laser using a 20 mm long, 3 mm diameter neodymium-doped yttrium aluminum garnet laser rod. This rod was placed in a liquid cooling chamber using a water-white-emulsion-paint mix. This mix provides cooling for the laser crystal and also doubles as a diffuse light scattering liquid. This enhances sunlight scattering and leads to a greater absorption in the laser rod. We numerically model the solar absorption in the laser rod using a ray-tracing model and predict a 2.6 times enhancement in absorption when a 98% reflective diffuse scatter is modelled compared to 0% scattering. We experimentally demonstrated this, showing a 2.58 times increase in average output power of the solar laser compared to the use of pure water as a cooling liquid. Using the water-white-paint scattering cooling liquid, we demonstrated a laser with an output power of 2.3 W and with a collection efficiency of 27.5 W/m2. PMID- 29791378 TI - Design of an adjustable bipod flexure for a large-aperture mirror of a space camera. AB - An adjustable bipod flexure (ABF) technique for a large-aperture mirror of a space camera is presented. The proposed flexure mount can decrease the surface distortions caused by the machining error and the assembly error of the mirror assembly (MA) in a horizontal optical testing layout. Through the analysis of the compliance matrix of conventional bipod flexure, the positional relationship between the rotation center and the apex of the flexure is investigated. Then, the principle of the adjustable flexure, known as the trapezoidal switching principle, is proposed based on the analysis result. The structure and application of the flexure are also described. The optical performance of the mirror mounted by the adjustable flexures in different misalignments was performed using finite element methods. The result shows that the astigmatic aberration due to gravity is effectively reduced by adjusting the mount, and the root-mean-square value of the mirror can be minimized with the misalignment between the flexure pivot and the neutral plane minimized. New monolithic bipod flexures, based on the optimal regulating variable Deltau according to the measurement results, are manufactured to replace the ABFs to secure the mirror's safety against launch loads. Modal analysis verified the mechanical safety of the MA with respect to the new monolithic flexures. PMID- 29791379 TI - Decision feedback equalizer for holographic data storage. AB - Holographic data storage (HDS) has attracted much attention as a next-generation storage medium. Because HDS suffers from two-dimensional (2D) inter-symbol interference (ISI), the partial-response maximum-likelihood (PRML) method has been studied to reduce 2D ISI. However, the PRML method has various drawbacks. To solve the problems, we propose a modified decision feedback equalizer (DFE) for HDS. To prevent the error propagation problem, which is a typical problem in DFEs, we also propose a reliability factor for HDS. Various simulations were executed to analyze the performance of the proposed methods. The proposed methods showed fast processing speed after training, superior bit error rate performance, and consistency. PMID- 29791380 TI - Polarization-sensitive laser feedback interferometry for specular reflection removal. AB - Specular reflection from the surface of targets or prepared specimens represents a significant problem in optical microscopy and related optical imaging techniques as usually the surface reflection does not contribute to the desired signal. Solutions exist for many of these imaging techniques; however, remedial techniques for imaging based on laser feedback interferometry (LFI) are absent. We propose a reflection cancellation technique based on crossed-polarization filtering that is tailored for a typical LFI configuration. The technique is validated with three experimental designs, and a significant improvement of about 40 dB in the ratio of the diffuse and specular LFI signal is observed. Applications of this principle extend from specular reflection removal to characterization of target materials in industrial to biomedical domains. PMID- 29791381 TI - Fringe projection system for high-temperature workpieces-design, calibration, and measurement. AB - In the Collaborative Research Centre 1153, Tailored Forming, the geometry of hot measurement objects needs to be captured quickly, areally, and with high precision. The documentation of the hybrid components' shrinkage behavior directly after the forming process can yield insight into the development of residual stresses. In this paper, we present a fringe projection measurement setup designed for the topography measurement of high-temperature steel shafts, comprising two cameras with different lenses and a projector. In order to separate the measurement signal from light by self-radiation, a green bandpass filter is installed in front of the measurement camera's sensor. The optical sensors are protected from the measurement object's temperature and possible scale by a glass panel and a working distance of at least 250 mm. High-resolution measurements are guaranteed due to a telecentric measurement camera and a triangulation angle of about 30 degrees . The triangulation angle requires an additional entocentric calibration camera to provide a highly accurate projector model estimation. Special attention is therefore devoted to the developed calibration routine, the glass panel effect, and the applied distortion models. The quality of the calibration routine is validated by a reference sphere measurement. Furthermore, the geometry data of a red-glowing heating rod (approximately 1020 degrees C) is acquired to demonstrate the performance of the presented system. In future applications, the presented setup will be used with a force-controlled clamping unit to enable secure and position stable topography acquisition of hot measurement objects. PMID- 29791382 TI - Polychromatic wave-optics models for image-plane speckle. 1. Well-resolved objects. AB - Polychromatic laser light can reduce speckle noise in wavefront-sensing and imaging applications that use direct-detection schemes. To help quantify the achievable reduction in speckle, this paper investigates the accuracy and numerical efficiency of three separate wave-optics methods. Each method simulates the active illumination of extended objects with polychromatic laser light. In turn, this paper uses the Monte Carlo method, the depth-slicing method, and the spectral-slicing method, respectively, to simulate the laser-object interaction. The limitations and sampling requirements of all three methods are discussed. Further, the numerical efficiencies of the methods are compared over a range of conditions. The Monte Carlo method is found to be the most efficient, while spectral slicing is more efficient than depth slicing for well-resolved objects. Finally, Hu's theory is used to quantify method accuracy when possible (i.e., for well-resolved objects). In general, the theory compares favorably to the simulation methods. PMID- 29791383 TI - Polychromatic wave-optics models for image-plane speckle. 2. Unresolved objects. AB - Polychromatic laser light can reduce speckle noise in many wavefront-sensing and imaging applications. To help quantify the achievable reduction in speckle noise, this study investigates the accuracy of three polychromatic wave-optics models under the specific conditions of an unresolved object. Because existing theory assumes a well-resolved object, laboratory experiments are used to evaluate model accuracy. The three models use Monte-Carlo averaging, depth slicing, and spectral slicing, respectively, to simulate the laser-object interaction. The experiments involve spoiling the temporal coherence of laser light via a fiber-based, electro optic modulator. After the light scatters off of the rough object, speckle statistics are measured. The Monte-Carlo method is found to be highly inaccurate, while depth-slicing error peaks at 7.8% but is generally much lower in comparison. The spectral-slicing method is the most accurate, always producing results within the error bounds of the experiment. PMID- 29791384 TI - Copying of holograms by spot scanning approach. AB - To replicate holograms, contact copying has conventionally been used. In this approach, a photosensitive material is fixed together with a master hologram and illuminated with a coherent beam. This method is simple and enables high-quality copies; however, it requires a large optical setup for large-area holograms. In this paper, we present a new method of replicating holograms that uses a relatively compact optical system even for the replication of large holograms. A small laser spot that irradiates only part of the hologram is used to reproduce the hologram by scanning the spot over the whole area of the hologram. We report on the results of experiments carried out to confirm the copy quality, along with a guide to design scanning conditions. The results show the potential effectiveness of the large-area hologram replication technology using a relatively compact apparatus. PMID- 29791386 TI - Single-frequency 3D synthetic aperture imaging with dynamic metasurface antennas. AB - Through aperture synthesis, an electrically small antenna can be used to form a high-resolution imaging system capable of reconstructing three-dimensional (3D) scenes. However, the large spectral bandwidth typically required in synthetic aperture radar systems to resolve objects in range often requires costly and complex RF components. We present here an alternative approach based on a hybrid imaging system that combines a dynamically reconfigurable aperture with synthetic aperture techniques, demonstrating the capability to resolve objects in three dimensions (3D), with measurements taken at a single frequency. At the core of our imaging system are two metasurface apertures, both of which consist of a linear array of metamaterial irises that couple to a common waveguide feed. Each metamaterial iris has integrated within it a diode that can be biased so as to switch the element on (radiating) or off (non-radiating), such that the metasurface antenna can produce distinct radiation profiles corresponding to different on/off patterns of the metamaterial element array. The electrically large size of the metasurface apertures enables resolution in range and one cross range dimension, while aperture synthesis provides resolution in the other cross range dimension. The demonstrated imaging capabilities of this system represent a step forward in the development of low-cost, high-performance 3D microwave imaging systems. PMID- 29791385 TI - Airborne lidar detection and mapping of invasive lake trout in Yellowstone Lake. AB - The use of airborne lidar to survey fisheries has not yet been extensively applied in freshwater environments. In this study, we investigated the applicability of this technology to identify invasive lake trout (Salvelinus namaycush) in Yellowstone Lake, Yellowstone National Park, USA. Results of experimental trials conducted in 2004 and in 2015-16 provided lidar data that identified groups of fish coherent with current knowledge and models of lake trout spawning sites, and one identified site was later confirmed to have lake trout. PMID- 29791387 TI - Shape reconstruction based on zero-curl gradient field estimation in a fringe reflection technique. AB - A novel shape reconstruction method based on zero-curl gradient field estimation is presented in this paper. Zero-curl field estimation makes the most of curl information to obtain the ideal gradient data, and achieves the reconstruction with the quality map path integration method. In the estimation process, an algebraic approach is adopted to enforce integrability, which maintains the local information well. Moreover, we use the residual gradients of surface obtained from the Southwell zonal reconstruction algorithm as the raw gradient data in zero-curl field estimation, which has a stable tradeoff between smoothness and local shape confinement. The performance of the proposed method over antinoise capability is discussed and demonstrated by the simulations. The measurement experiment of an ultraprecision sphere mirror identifies the validity over general shapes, and the reconstruction results of hyperbolic surface with a local shape map demonstrate the better performance on local details retention. Therefore, this method performs well in handling complex objects with local mutation regions and high accuracy requirement of local information in practical measurement. PMID- 29791388 TI - Calibration of focusing lens artifacts in a dual rotating-compensator Mueller matrix ellipsometer. AB - A focusing lens consisting of two or more elements is widely used in ellipsometers for spatial resolution. In a typical ellipsometer layout, a lens is placed before the sample to focus light emerging to the sample, and another after the sample to collect the scattered light from the sample. Accurately calibrating the artifacts of the focusing lens is of great importance. In this paper, a method to improve calibration accuracy is proposed. A general analytical model is deduced to describe the artifacts of the focusing lens. This model can be applied to a system model of a dual rotating-compensator Mueller matrix ellipsometer. By adding a uniaxial crystal to calibration samples, with its optical axis neither parallel nor perpendicular to the incident plane, we can better separate artifacts from the lens before and after the sample. The system model also includes depolarization effects due to a finite numerical aperture (NA) that is related to the focusing lens. Similar effects due to the finite spectral bandwidth are also considered. Our simulation's results have validated the proposed method. PMID- 29791390 TI - Rapid optical imaging of polycrystalline material structures. AB - The physical properties of polycrystalline materials that are widely used in various optical applications are determined by their structure, wherein grain size and form and grain boundaries play a crucial role. Currently, there is no simple and fast method to generate a direct image of polycrystalline material structures. In this study, we propose a method for direct optical imaging of a crystalline material structure based on the difference between the optical properties of the grains and grain boundaries near the fundamental absorption edge of the material. Our results indicate the possible utility of the method in diverse imaging applications. PMID- 29791389 TI - Gaussian probe beam with high spherical aberration for glucose concentration measurement. AB - We demonstrate that an optical probe beam with high spherical aberration used for glucose concentration measurements gives better sensitivity compared to a probe beam free of aberrations, under similar conditions. We place a singlet focusing lens at a large distance from a laser source with a Gaussian intensity profile to obtain a spherically aberrated probe beam with negligible truncation. The aberrated probe beam propagates through a transparent liquid sample. Intensity profiles of the transmitted beam are recorded by means of a homodyne profiler to perform the glucose concentration measurements accurately. PMID- 29791391 TI - Effects of aberrations on effective point spread function in STED microscopy. AB - Like other imaging techniques, stimulated emission depletion (STED) microscopy suffers from aberrations. While their effects on depletion patterns have been explicitly investigated, the study on how aberrations affect the effective point spread function (PSF) in STED microscopy is still missing. For STED researchers, however, this study is beneficial, as it directly bridges image qualities and aberrations. In this paper, we quantitatively analyze the effects of primary aberrations, including astigmatism, coma, trefoil, and spherical aberration, in two-dimensional (2D) and three-dimensional (3D) STED microscopy, and further discuss the corresponding aberration tolerance. Specifically, attention is given to the modification of the shape, the size, and the peak intensity of the effective PSF in the presence of these aberrations. PMID- 29791392 TI - Wide field-of-view crossed Dragone optical system using anamorphic aspherical surfaces. AB - A side-fed crossed Dragone telescope provides a wide field of view. This type of telescope is commonly employed in the measurement of cosmic microwave background polarization, which requires an image-space telecentric telescope with a large focal plane over broadband coverage. We report the design of a wide field-of-view crossed Dragone optical system using anamorphic aspherical surfaces with correction terms up to the 10th order. We achieved a Strehl ratio larger than 0.95 over 32*18 square degrees at 150 GHz. This design is an image-space telecentric and fully diffraction-limited system below 400 GHz. We discuss the optical performance in the uniformity of the axially symmetric point-spread function and telecentricity over the field of view. We also address the analysis to evaluate the polarization properties, including the instrumental polarization, extinction rate, and polarization angle rotation. This work is a part of a program to design a compact multi-color wide-field-of-view telescope for LiteBIRD, which is a next-generation cosmic microwave background (CMB) polarization satellite. PMID- 29791393 TI - On the use of deep neural networks in optical communications. AB - Information transfer rates in optical communications may be dramatically increased by making use of spatially non-Gaussian states of light. Here, we demonstrate the ability of deep neural networks to classify numerically generated, noisy Laguerre-Gauss modes of up to 100 quanta of orbital angular momentum with near-unity fidelity. The scheme relies only on the intensity profile of the detected modes, allowing for considerable simplification of current measurement schemes required to sort the states containing increasing degrees of orbital angular momentum. We also present results that show the strength of deep neural networks in the classification of experimental superpositions of Laguerre-Gauss modes when the networks are trained solely using simulated images. It is anticipated that these results will allow for an enhancement of current optical communications technologies. PMID- 29791394 TI - Optical measurement of high-temperature melt flow rate. AB - This paper presents an optical method and system for contactless measurement of the mass flow rate of melts by digital cameras. The proposed method is based on reconstruction of melt stream geometry and flow velocity calculation by cross correlation, and is very cost-effective due its modest hardware requirements. Using a laboratory test rig with a small inductive melting pot and reference mass flow rate measurement by weighing, the proposed method was demonstrated to have an excellent dynamic response (0.1 s order of magnitude) while producing deviations from the reference of about 5% in the steady-state flow regime. Similar results were obtained in an industrial stone wool production line for two repeated measurements. Our method was tested in a wide range of melt flow rates (0.05-1.2 kg/s) and did not require very fast cameras (120 frames per second would be sufficient for most industrial applications). PMID- 29791395 TI - Fiber-optic Fabry-Perot pressure sensor based on low-temperature co-fired ceramic technology for high-temperature applications. AB - In this study, a novel batch-producible fiber-optic Fabry-Perot (FP) pressure sensor based on a low-temperature co-fired ceramic technology is proposed and experimentally demonstrated for high-temperature applications. The sensor is fabricated by inserting a well-cut single-mode fiber (SMF) into a zirconia fiber ferrule, followed by insertion of the overall structure into an alumina sensor head. The FP cavity in the sensor is formed by placing the end face of the SMF in parallel to the diaphragm. The external pressure can be detected by demodulating the FP cavity length of the sensor. A theoretical analysis indicates that the pressure sensitivity can be designed flexibly by adjusting the parameters of the ceramic diaphragm, radius, and thickness. Experimental results demonstrate that the pressure sensor exhibits a high linear sensitivity of approximately 0.1 MUm/kPa at room temperature in the pressure range up to 160 kPa. The repeatability error and nonlinear error of three repeatable experiments are approximately 2.60% and smaller than 0.101%, respectively. The temperature coefficient and coefficient of the pressure-sensitivity changes with temperature are 0.023 MUm/ degrees C and 0.205 nm/(kPa degrees C) in the temperature range of 20 degrees C-300 degrees C. PMID- 29791396 TI - Effective freeform TIR lens designed for LEDs with high angular color uniformity. AB - Most LED luminaires face the problem of color nonuniformity in illumination fields, which seriously degrades their lighting quality. To address this issue, we proposed a freeform TIR lens, which could be applied to the most widely adopted phosphor-converted LEDs and multicolor LED arrays. Based on light pattern overlap and energy mapping, the novel TIR lens comprised the freeform panel and the collimator. Analysis of angular color uniformity (ACU), based on a phosphor converted white LED model, proved that the normalized standard deviation (NSD) of the LED integrated with the freeform TIR lens significantly decreased from 0.792 to 0.232, compared with the NSD of the traditional TIR lens. Moreover, the proposed TIR lens was also applied to a multiple LED array for color mixing. Both the theoretical analysis and simulation results demonstrated their capability to enhance the ACU. These results demonstrated the effectiveness of the proposed method to improve the uniformity of the LED sources regardless of single or multiple LEDs. The improved lighting quality guarantees good employment of LEDs, especially in the fields of entertainment and architectural lighting. PMID- 29791397 TI - High-repetition-rate single-frequency Ho:YAG MOPA system. AB - A stable, 2.09 MUm single-frequency Ho:YAG master oscillator and power amplifier (MOPA) system at a pulse repetition frequency of 1.25 kHz is demonstrated. The maximum output energy of the single-frequency injection-seeded laser is 13.76 mJ, and the corresponding pulse width is 178.9 ns. The seed laser is a continuous wave Ho:YAG non-planar ring oscillator laser. The half-width of the pulse spectrum is measured to be 2.65 MHz by using the heterodyne technique, which is about 1.06 times Fourier transform limited. PMID- 29791398 TI - Ultralow chirp photonic crystal fiber Mach-Zehnder interferometer. AB - A photonic crystal fiber Mach-Zehnder interferometer design was optimized to obtain high performance and ultralow chirp. Two long-period gratings were used to excite the cladding modes, and the rich structure of the cladding was tailored to obtain a slightly chirped free spectral range, as required by the Telecommunication Standardization Sector of the International Telecommunication Union (ITU-T) Norm G.694.1. Finally, a fabrication tolerance analysis was performed. The advantages of the proposed device are an ultralow chirp, high bandwidth, and fabrication robustness tolerance. PMID- 29791399 TI - Highly efficient in situ oxidization of metal ions in porous media with high power laser. AB - Metal ions in ground are hard to remove and constitute a serious environmental challenge. This paper reports a new laser-based method for in situ soil decontamination at high efficiency, in which a focused CO2 laser is used to oxidize metal contaminants from soil and fuse them with silica (base materials of soil), thus preventing undesired transport of metal ions within soil. Three types of metal ions (copper, nickel, and cadmium) adsorbed on porous silica plates are exposed to continuous laser irradiation. The lithographic mode of operation allows the accurate quantitation of laser effects. The effects of power, speed, frequency, and energy consumption on the efficiency of oxidation have been examined with high accuracy. The affected area increases with increases in laser power and decreases in scan speed and frequency. This method is promising for large scale in situ soil recovery due to high efficient oxidation of metal ions by high power laser. PMID- 29791400 TI - Temperature-independent hygrometry using micromachined photonic crystal fiber. AB - An in-fiber Mach-Zehnder interferometer (MZI) is proposed and experimentally demonstrated for relative humidity (RH) and temperature measurements. The MZI is formed by a grapefruit-shaped photonic crystal fiber (G-PCF) cascaded with a short section of multimode fiber that serves as a mode coupler. To enhance sensitivity to humidity, femtosecond laser micromachining was performed to remove a portion of cladding of the G-PCF to expose its core to the ambient medium. The output interference spectrum is fast Fourier transformed to produce a spatial frequency spectrum that describes the intensity composition of the cladding modes in the MZI. In our investigation, it was observed that the interference dip intensity has a sensitivity of -0.077 dB/% RH to the change of RH in the range of 25%-80% RH, whereas the dip wavelength has a temperature sensitivity of ~3.3 pm/ degrees C in the range of 25 degrees C-70 degrees C. In addition, the dip intensity was insensitive to temperature. These characteristics have provided convenience in eliminating temperature cross talk and achieving accurate humidity measurement. PMID- 29791401 TI - Investigation of index change in compression molding of As40Se50S10 chalcogenide glass. AB - Chalcogenide glasses are emerging as alternative materials for low-cost and high volume glass molding processes for infrared optics. In precision glass molding, it is well documented that the refractive index variation in the molded elements can lead to substantial amounts of aberrations. The variation has such a significant effect that the optical designs with molded lenses need to be carefully considered and compensated for index variation to achieve targeted optical performance. This research is aimed to evaluate the refractive index change of a chalcogenide glass during the molding process by both finite element method-based simulation and optical experiment. First, a set of mold inserts was designed and machined by high-speed single-point diamond milling. The structure of the lower mold insert was semiclosed and detachable, which facilitated the molded infrared prisms' release from the mold. Second, finite element method simulation was implemented to predict the refractive index change during the cooling phase by using the Tool-Narayanaswamy-Moynihan model for structural relaxation behavior. It was confirmed that refractive index variation occurred inside the molded wedge due to rapid thermal cycling. However, the amount of variation in the molded element indicates that the refractive index change during the molding process was not uniform. Finally, the refractive index of the molded wedge was measured by an optical setup. The results showed that the index shift is approximately -0.0226 for As40Se50S10, which matched the numerical result by simulation. Compared with oxide glass materials, the index drop of As40Se50S10 has a significant effect on optical performance of molded optics, and the postmolding refractive index should be taken into account in the optical design. In summary, the results presented in this article provided reliable references for refractive index change of As40Se50S10 glass, crucial for precision glass molding or similar applications. PMID- 29791402 TI - Determination of the damage growth threshold of multilayer dielectric gratings by picosecond laser pulses based on saturation damage size analysis. AB - We propose two efficient methods of determining damage growth threshold (DGT) based on the saturation damage size analysis (SDSA) for multilayer dielectric gratings by picosecond pulsed lasers. The damage size at laser fluences above DGT increases with the shot number and finally saturates due to the Gaussian focal spot. The DGT is extracted by mapping the boundary of a saturation damage site obtained at single fluence to the beam profile, which is called the monofluence SDSA method. Meanwhile, the saturation damage size decreases when reducing laser fluence. The fitting and extrapolation of the saturation damage sizes at different fluences are also useful to accurately determine the DGT, which is called the multifluence SDSA method. Although the saturation damage site is asymmetric, the DGTs measured with two SDSA methods are almost identical for the same axis, and both are in very good agreement with those obtained with the growth probability method. The underlying mechanisms and advantages of two SDSA methods are extensively discussed. The consistence of two SDSA methods in determining DGT is attributed to the same morphology of the initial damage and the saturation damage boundary, as well as the local damage dynamics. The relation of the lifetime damage threshold and DGT obtained with the SDSA method is also revealed. PMID- 29791403 TI - Quality enhancement and GPU acceleration for a full-color holographic system using a relocated point cloud gridding method. AB - The calculation of realistic full-color holographic displays is hindered by the high computational cost. Previously, we suggested a point cloud gridding (PCG) method to calculate monochrome holograms of real objects. In this research, a relocated point cloud gridding (R-PCG) method is proposed to enhance the reconstruction quality and accelerate the calculation speed in GPU for a full color holographic system. We use a depth camera to acquire depth and color information from the real scene then reconstruct the point cloud model virtually. The R-PCG method allows us to classify groups of object points with the same depth values into grids in the red, green, and blue (RGB) channels. Computer generated holograms (CGHs) are obtained by applying a fast Fourier transform (FFT) diffraction calculation to the grids. The feasibility of the R-PCG method is confirmed by numerical and optical reconstruction. PMID- 29791404 TI - Third-order aberration coefficients of a thick lens with a given value of its focal length. AB - The formulas are derived for calculation of the third-order aberration (Seidel) coefficients for a thick spherical lens in air with a given value of its focal length and for an object at infinity in this paper. The explicit analytic dependence of individual aberration coefficients on a lens thickness is derived. Equations were described for the re-calculation of aberration coefficients for a different value of focal length and different values of entrance pupil and object positions. Such formulas make it possible to analyze analytically an influence of the lens thickness on lens aberration properties and the replacement of a thin lens optical system by a thick lens model. PMID- 29791405 TI - Local blur analysis and phase error correction method for fringe projection profilometry systems. AB - We introduce a flexible error correction method for fringe projection profilometry (FPP) systems in the presence of local blur phenomenon. Local blur caused by global light transport such as camera defocus, projector defocus, and subsurface scattering will cause significant systematic errors in FPP systems. Previous methods, which adopt high-frequency patterns to separate the direct and global components, fail when the global light phenomenon occurs locally. In this paper, the influence of local blur on phase quality is thoroughly analyzed, and a concise error correction method is proposed to compensate the phase errors. For defocus phenomenon, this method can be directly applied. With the aid of spatially varying point spread functions and local frontal plane assumption, experiments show that the proposed method can effectively alleviate the system errors and improve the final reconstruction accuracy in various scenes. For a subsurface scattering scenario, if the translucent object is dominated by multiple scattering, the proposed method can also be applied to correct systematic errors once the bidirectional scattering-surface reflectance distribution function of the object material is measured. PMID- 29791406 TI - Controllable long focal length microlens based on thermal expansion. AB - A novel method to fabricate a microlens array with a long focal length has been developed in this paper. It is based on the fabricating and heating of a microlens consisting of two materials with a great difference in coefficient of thermal expansion. A thermal expansion process leads to considerable deformation of the microlens surface and significant increase in focal length, which could be controlled by altering the processing temperature. Cylindrical polymeric microlens arrays with different focal lengths were successfully fabricated. By measuring the focal length and temperature dependence of the cylindrical microlens geometry, the formation mechanism was analyzed and validated. While the temperature is ranged from 20 degrees C to 50 degrees C, the focal length of the cylindrical microlens has been extended by 38.2% and the longest focal length was obtained up to 6.6 mm for the microlens with a linewidth of 240 MUm. PMID- 29791407 TI - Stokes polarimeter performance: general noise model and analysis. AB - We calculate the photometric Stokes parameter covariance matrices and SNRs estimated by polarimeters exposed to general noise distributions, such as mixed Poisson-Gaussian (PG) noise. The measurement model includes the effects of optical losses and detector quantum efficiency, enabling quantitative comparison of instruments that have different photometric efficiencies. We demonstrate this capability by comparing the performance of many common polarimeter configurations, including diattenuator-based systems, such as Azzam's four detector polarimeter [Opt. Lett.10, 309 (1985)OPLEDP0146 959210.1364/OL.10.000309] and Kudenov's stacked photovoltaic polarimeter [Opt. Express24, 14737 (2016)OPEXFF1094-408710.1364/OE.24.014737]. Working with the full covariance matrix under mixed PG noise, we also show that instruments optimized under assumptions of Gaussian noise simultaneously exhibit optimal behavior under Poisson noise. PMID- 29791408 TI - Correction of phase-delay distortion for alpha-beta circular scanning. AB - alpha-beta circular scanning with a large scanning field of view and high reliability can be widely applied in laser scanning imaging systems and laser processing. However, mechanical inertia of the galvanometers introduces phase delay and ultimately leads to scanning distortions in alpha-beta circular scanning in both constant angular velocity scanning (CAVS) and constant line velocity scanning (CLVS). To compensate for the phase-delay distortions, two correction models are respectively proposed for CAVS and CLVS, which utilize phase-frequency relationships based on the galvanometer's transfer function. Experimental results show that the presented models can effectively correct rotation distortion in CAVS and tortuosity distortion in CLVS. The correction of phase-delay distortion can improve the image quality and refine positioning accuracy in laser scanning systems. PMID- 29791409 TI - Measurement of three-dimensional wavefronts using the Ichikawa-Lohmann-Takeda solution to the irradiance transport equation. AB - In this paper, we use the irradiance transport equation and the Fourier transform based experimental solution given by Ichikawa-Lohmann-Takeda. We analyze experimental factors such as the digital filter, the introduced error for the rotation and period of the Ronchi ruling, and a new method is demonstrated for the measurement of 3D wavefront information. PMID- 29791410 TI - Fluorescence resonance energy-transfer-based fluoride ion sensor. AB - The present work describes an energy-transfer-based fluoride sensor using the highly photo-stable Coumarin 540a (C540a)-Rhodamine 6g (Rh6g) dye pair. Rh6g exhibits a decrease in fluorescence emission, whereas C540a shows no change in response to fluoride. The increase in fluoride concentration decreases the energy transfer efficiency between the C540a donor and Rh6g acceptor in acetonitrile, leading to a subsequent recovery of fluorescence emission from C540a molecules. The sensing mechanism using fluorescence resonance energy transfer is found to be highly specific towards fluoride detection when compared to the response towards other anions. The fluorescence emission of both dyes is monitored to enable fluoride detection within a broad range. PMID- 29791411 TI - Optical nondestructive dynamic measurements of wafer-scale encapsulated nanofluidic channels. AB - Nanofluidic channels are of great interest for DNA sequencing, chromatography, and drug delivery. However, metrology of embedded or sealed nanochannels and measurement of their fill-state have remained extremely challenging. Existing techniques have been restricted to optical microscopy, which suffers from insufficient resolution, or scanning electron microscopy, which cannot measure sealed or embedded channels without cleaving the sample. Here, we demonstrate a novel method for accurately extracting nanochannel cross-sectional dimensions and monitoring fluid filling, utilizing spectroscopic ellipsometric scatterometry, combined with rigorous electromagnetic simulations. Our technique is capable of measuring channel dimensions with better than 5-nm accuracy and assessing channel filling within seconds. The developed technique is, thus, well suited for both process monitoring of channel fabrication as well as for studying complex phenomena of fluid flow through nanochannel structures. PMID- 29791413 TI - Measurement of optical fiber parameters and thermal core diffusion characteristics by digital image processing. AB - The simultaneous measurement of the numerical aperture (NA) and mode field diameter (MFD) of single-mode fibers was performed on several commercial fibers by means of digital image processing of the output light projected into a screen. In addition, the changes induced by core diffusion in an ultra-high (UH) NA fiber at several heat depositions from a CO2 laser source were measured. The measurement method was demonstrated to be useful to monitor the adiabaticity of this process, by taking the product of the NA and MFD to verify if it remains constant. The method provides a cheap alternative to measure these optical fiber parameters by using simple optomechanical elements and a readily available smartphone camera, and it can be easily implemented in the laboratory. PMID- 29791412 TI - Shock-wave imaging by density recovery from intensity measurements. AB - A method for quantitative estimation of density variation in high-speed flow, which uses light as an interrogating tool, is described. The wavefront distortion of the interrogating beam induced by the compressible flow field is estimated quantitatively, in which the density gradient of the flow field is seen as refractive-index gradient by the probing beam. The distorted wavefront is measured quantitatively by using the cross-sectional intensities of the distorted wavefront along the optical axis. Iterative algorithms are developed using both deterministic (Gauss-Newton) and stochastic (ensemble Kalman filter) update strategies to recover unknown parameters such as the phase of the wavefront or the refractive index distribution in the flow directly from the measured intensities. With phase recovered in the first step, a ray tomography algorithm is used to obtain the refractive index and density distributions in the flow from the phase. Experiments are conducted to quantitatively visualize the shock-wave induced flow field in a shock-tunnel facility. The reconstructed density cross sections, obtained using different reconstruction methods, are presented and compared with those obtained by solving the Navier-Stokes equation using computational fluid dynamic routines. It is observed that the iterative algorithms always outperform those depending on solution of the transport-of intensity equation. In particular, when using the iterative algorithms, the stochastic search scheme outperforms the Gauss-Newton method. PMID- 29791414 TI - Calibrating a paracatadioptric camera by the property of the polar of a point at infinity with respect to a circle. AB - Two methods are presented for calibrating a paracatadioptric camera. A sphere in 3D space is projected to two parallel circles on which two tangents of a point and its antipode are parallel on the unit viewing sphere and intersect at the point at infinity. The direction of the polar of the point at infinity is orthogonal to the direction of the point at infinity with respect to the circle. The imaged circular points and orthogonal vanishing points can be obtained to solve the intrinsic camera parameters. Simulations and real data were used to demonstrate the effectiveness of the two algorithms. PMID- 29791416 TI - Oncological outcomes in extended time intervals betweenpreoperative chemoradiotherapy with capecitabine and surgery inoperable rectal adenocarcinoma. AB - OBJECTIVE: To assess whether extended time intervals (8-12, 13-20 and >20 weeks) between the end of neoadjuvant chemoradiotherapy and surgery affect overall survival, disease-free survival. MATERIALS AND METHODS: Retrospective study in 120 patients with rectal adenocarcinoma without evidence of metastasis (T1-4/N0 2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant chemoradiotherapy with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at the National Cancer Institute of Peru. Dates were evaluated by Kaplan-Meier method, log- rank test and Cox regression analysis. RESULTS: Of the 120 patients, 70 were women (58%). The median age was 63(26-85) years. All received neoadjuvant chemoradiotherapy. No significant difference was found between the association of the median radial (0.6, 0.7 and 0.8 cm; p=0.826) and distal edge (3.0, 3.5 and 4.0 cm; p=0.606) with time interval groups and similarly the mean resected (18.8, 19.1 and 16.0; p=0.239) and infiltrated nodules (1.05, 1.29 and 0.41); p=0.585). The median follow-up time of overall survival and desease free survival was 40 and 37 months, respectively. No significant differences were observed in overall survival (79.0%, 74.6% and 71.1%; p=0.66) and disease-free survival (73.7%, 68.1% and 73.6%; p=0.922) according to the three groups studied at the 3-year of follow-up. CONCLUSIONS: We found that widening the time intervals between the end of neoadjuvant chemoradiotherapy and surgery at 24 weeks does not affect the overall survival, disease-free survival and pathological outcomes. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery. PMID- 29791418 TI - [ERCP success after 72 hours of pre-cut]. AB - INTRODUCTION: Despite the advances of bile duct catheterization, its success is still not guaranteed. Few studies have been published regarding a second ERCP attempt, however those reports enhance the catheterization success Objective: To determine whether an ERCP performed 72 hours after a first precut papillotomy enhances the bile duct catheterization. MATERIAL AND METHODS: A cohort study was performed including all patients that had ERCP with precut papilotomy without catheterization of the bile duct and 72 hours later were programmed to a new ERCP between September 2015 and September 2016. These patients did not have any distinctive characteristic such as age, gender or anatomy that were associated with the failure to catheterize the bile duct, compared to the general population. RESULT: 16 patients were included with a mean age of 61,3 years (SD: 10,6), bile duct catheterization was successful in 14 cases. No complications presented after precut papilotomy. Both failures went to surgery. CONCLUSIONS: Our experience about an 87% successful bile duct catheterization, 72 hours after precut papillotomy allows us to suggest it as an alternative before considering surgery. PMID- 29791417 TI - [Accuracy of ASGE predictors in diagnosis of coledocolithiasis in a public hospital of Lima, Peru]. AB - BACKGROUND: The predictors proposed by the American Society of Gastrointestinal Endoscopy (ASGE) are commonly used topredict the presence and management of choledocholithiasis. OBJECTIVE: To evaluate the performance and precision of thepredictors of choledocholithiasis proposed by ASGE. MATERIALS AND METHODS: Prospective and longitudinal study performed ata third level hospital during January 2015 to June 2017. All patients with high and intermediate probability of choledocholithiasiswho underwent endoscopic retrograde cholangiopancreatography (ERCP) were included according to the criteria proposedby the ASGE. RESULTS: A total of 246 patients with suspected choledocholithiasis were analyzed. Of the 228 patients withhigh probability criteria 144 (63.2% = performance) had choledocholithiasis in ERCP with an accuracy of 62% (sensitivity:94.1% and specificity: 9.7%). Among the 18 patients with intermediate probability criteria, 9 (50% = performance) hadcholedocholithiasis with an accuracy of 38% (sensitivity: 5.9% and specificity: 90.3%). In the multivariate analysis, the presenceof stone in the bile duct by ultrasonography (OR: 1.937, 95% CI 1.048 3.580, p=0.035) and age 55 and over (OR: 2.121, 95%CI, 1.101-4.088, p=0.025) were the strongest predictors for choledocholithiasis. CONCLUSIONS: The application of the criteriaof the ASGE to predict the probability of choledocholithiasis, in our population has a performance greater than 50%, however,it is necessary to improve these parameters to avoid an unnecessary performance of ERCP. PMID- 29791419 TI - [Endoscopic treatment of rectal neuroendocrine tumors: multicentre study in Peru]. AB - INTRODUCTION: The incidental detection of rectal neuroendocrine tumors (NET) has increased but there is no proper consensus about treatment. OBJECTIVE: Evaluate the efficacy and safety of endoscopic treatment for rectal NET less than 20 mm, with emphasis in "standardized treatment". MATERIAL AND METHODS: From January 2012 to April 2016, we included patients with rectal NET less than 20 mm resected by conventional EMR, EMR-B and ESD. We considered as "standardized treatment" the one that has precise indication and technical rigor (EMR-B for lesions <= 10 mm and ESD for lesions between 11 and 20 mm). We evaluate complete resection rates and incidence of complications. RESULTS: 23 patients with 23 rectal NET were included. The mean age was 52.96 +/- 12.44 years. The mean tumor diameter was 8.8 +/- 3.4 mm. The complete resection rates by conventional EMR, EMR-Band ESD were 50 (3/6), 92.8 (13/14) and 100% (3/3), respectively; while by standardized and conventional treatment were 100 (14/14) and 55.5% (5/9), respectively. Complications occurred in 4 cases (17.4%), bleeding in 2 and perforation in 2, all of them solved by endoscopy. CONCLUSIONS: Endoscopic treatment by EMR-B and ESD is efficacious and safe for rectal NET <= 20 mm. Standardized treatment improve the efficacy of endoscopic treatment. PMID- 29791420 TI - Upper gastrointestinal endoscopy applied in pediatrics: endoscopic and histological findings, including Helicobacter pylori. AB - OBJECTIVE: To present and discuss the endoscopic and histological results, as well as the incidence of Helicobacter pylori and other diseases, indications and characteristics of upper digestive endoscopies performed in children. MATERIAL AND METHODS: Twenty-five endoscopies were performed in children aged six months to 11 years (mean 7.69 years), from February 2013 to January 2016. In 200 patients, endoscopies were diagnostic and serial biopsies were performed (esophagus, stomach and duodenum), in 120 of them. RESULTS: The indication of endoscopy was diagnosed in 88.89% of the patients, and in 26 patients, a therapeutic procedure was performed. The most frequent endoscopic findings were esophagitis in 49 patients, gastritis in 84 and duodenitis in 16 patients. Four duodenal ulcers were diagnosed. In the therapeutic endoscopies, six gastrostomies were performed, 14 foreign body withdrawals, five nasoenteral tube passages and esophageal dilatation. The H. pylori survey was performed by anatomopathological method and was positive in 26 (13%) of the 200 patients in whom it was searched. CONCLUSION: pediatric endoscopy is an important niche of the digestive endoscopy, where it is important to emphasize the relevance of the institutional structure that performs these procedures, in order to conduct them safely, being able to treat possible and feasible complications. PMID- 29791421 TI - [Autoimmune hepatitis recurrence after liver transplantation: 15 years experience in Peru]. AB - INTRODUCTION: The recurrence of autoimmune hepatitis (HAI) following liver transplantation occurs between 8-68%. In our experience, autoimmune liver diseases are a major indication of liver transplantation. OBJECTIVE: To determine the recurrence of autoimmune hepatitis in 15 years of experience and to evaluate the risk factors associated with the recurrence of HAI. MATERIALS AND METHODS: Retrospective, descriptive and cross-sectional study. From March 2000 to December 2015; 200 transplants were performed on 190 liver transplants; 36 patients were diagnosed for hepatic cirrhosis by HAI and underwent liver biopsy if transaminase (TGP-TGO >2 ULN) in 2 consecutive measurements. The diagnosis was made by histological criteria. RESULTS: The indication for hepatic transplantation for HAI was 19%. Mean age was 35 years (range 16-64 years) relationship between Sex F / M 2.2, the most common HAI subtype is type 1 (89%). The HAI histological recurrence was 31% (11/36). The mean follow-up was 54 months (range 8-169 months). CONCLUSIONS: Autoimmune hepatitis is the most frequent indication of liver transplantation in our experience, accounting for 19%. The recurrence of post-transplant HAI was 31%. No association was found between the degree of severity of histological activity in the explants and the type of HLA in the presentation of the recurrence. PMID- 29791422 TI - Prevalence of non A to E hepatitis in Mumbai, India. AB - INTRODUCTION: Acute viral hepatitis is a common problem in India. World wide data shows that 5 to 20 percent of this is caused by non A-E hepatitis. There is no data in India regarding non A-E hepatitis. We carried out this study to evaluate the epidemiology, clinical features, risk factors and outcome of non A-E hepatitis. MATERIAL AND METHODS: In this single centre study, we evaluated all patients admitted with features of acute viral hepatitis at our hospital between the period of February to July 2015. A detailed history about the epidemiology, risk factors and clinical features was done. Patients were evaluated with bilirubin, transaminases and prothrombin time. Each patient was investigated for IgM HAV, IgM HEV, HBsAg and Antibody against hepatitis C. Patients turning out negative were investigated for presence of autoimmune hepatitis or Wilson's disease. All viral markers were repeated a week later to confirm non A-E status. RESULTS: A total 265 patients were included of which 41 (15.4%) patients were non A-E hepatitis. They had higher age (28.55 vs 34.99, p<0.05) but similar gender and sub urban location. Median SEC classification was A2 in hepatitis A/E group as compared to A3 in non A-E group. The duration of symptoms and clinical features between the two groups were similar with Anorexia, Malasie, Nausea/vomiting being most common. The risk factors between the two groups were similar. The bilirubin and transaminases were non significantly lower than hepatitis A/E patients while albumin levels were significantly lower. The outcomes of both groups were similar with no mortality or fulminant hepatitis. CONCLUSION: Non A-E hepatitis patients tends to be older, lower SEC class and had lower albumin levels as compared to hepatitis A/E. PMID- 29791424 TI - [Primary biliary cholangitis. Part 2. State of the art, diagnosis, associated diseases, treatment and prognosis]. AB - Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others. The first line treatment is ursodeoxycholic acid (UDCA), that improves liver function tests and delay the progression to cirrhosis. Currently, there are new treatments and adjuvant therapies on study. The purpose of this review is to offer an update in this topic, which is very important in gastroenterology and internal medicine. We formed an interdisciplinary team to search in the data base Medline thorough PubMed with the keywords describe below, we made a critical lecture of the titles and abstracts of each article to write this paper. PMID- 29791423 TI - [Helicobacter pylori: How do we treat it in 2018?] AB - This work is a review on the basic aspects of the treatment of Helicobacter pylori, highlighting the causes of treatment failure and strategies exist to optimize the treatment according to the best evidence posted. Stands out the antimicrobial resistance as the main cause of treatment failure, as well as the different compartments where the microorganism is hosted. Shows major schemes currently available and how to choose therapies first, second, third line and rescue therapies. PMID- 29791425 TI - [Endoscopic submucosal dissection of a transpyloric early gastric cancer. A case report and literature review]. AB - The endoscopic sumucosal disection (ESD) is an advanced endoscopic technique that achieves the curative resection of superficial neoplasms of the gastrointestinal tract, getting block exeresis with margins free of neoplasia avoiding surgery. However, tumors located in the esophagogastric junction, or pylorus, are technically more complex to resect by ESD. When a neoplasm settles in the pylorus, the anatomical characteristics of this region can affect the adequate assessment of the margins and the performance of the procedure. We present the case of a 70-year-old male patient who, in a high digestive endoscopy, showed a flat multilobulated lesion of 18 mm x 10 mm, located mostly in the lower 2 quadrants of the pyloric canal and minimal compromise of the upper-posterior quadrant, it mainly covers the gastric side of the pyloric channel and extends into the duodenum. Therefore, it was decided to perform en bloc resection of the lesion with the endoscopic submucosal dissection technique. The ERBEJET system was used with a knife type Hybrid knife, saline injection with methylene blue diluted 0.04% on the distal margin, submucosal injection being complemented with 0.4% hyaluronic acid. A "capsule" or straight transparent distal plastic device was used to be able to pull the lesion and allow anterograde visualization of the margins of resection, including the intraduodenal portion, allowing adequate submucosal dissection. Histopathology showed a moderately differentiated tubular adenocarcinoma with surgical edges free of injury. Thanks to the DSE strategy used, our patient could benefit from the curative resection of his gastric cancer with preservation of the organ and with perfect functionality. This case, the first described in the country, shows the progress of national therapeutic endoscopy. PMID- 29791426 TI - [Familiar adenomatous polyposis: report of 2 cases]. AB - Familial Adenomatous polyposis (FAP) it is based on an autosomal dominant mutation which results in loss of function of theAPC tumor suppressor gene. On the other hand, Gardner syndrome is a type of FAP and is characterized for multiple colonic adenomatous polyps and extracolonic abnormalities as desmoid tumors, osteomas, lipomas, dental abnormalities, dermoid cysts and duodenal adenomas. This report aims to present two patients with FAP: The first one is a patient who presented with osteomas and hematochezia, being diagnosed with Gardner Syndrome after the colonoscopy. The second patient has a family history of colon cancer, who is diagnosed with FAP with tubular adenocarcinoma. We decide to report both cases due to the absence of previous reports in Peru. PMID- 29791427 TI - [Insulinoma found in patient with apparent mental disorder: a case report]. AB - Pancreatic Insulinoma is a neuroendocrine tumor of the beta cells of the islets of Langerhans, has an incidence of 4 cases per 1 000 000 persons. We report the case of a 36-year-old woman with altered behavior associated with melancholy. Psychiatry describes an abnormal mental examination and diagnosed double depression; however, the patient had the Whipple triad and insulin/glucose ratio higher than 0.3. The insulinoma was localized by magnetic resonance imaging and treated with surgery. Insulinomas can mimic mental disorders, making early diagnosis difficult. We compare health care data in our locality with others obtained from the global literature. We conclude that despite the technical limitations, insulinoma should be included in the differential diagnosis of mental disorders with hypoglycemia. PMID- 29791428 TI - [Acute liver failure as presentation of adult T-cell leukemia in an HTLV-1 patient]. AB - Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission. PMID- 29791429 TI - [Clinical practice guideline for the evaluation and management of upper gastrointestinal bleeding for the Peruvian Social Security (EsSalud)]. AB - OBJECTIVE: To provide evidence-based clinical recommendations for the evaluation and management of patients with upper gastrointestinal bleeding (UGB) in the Peruvian Social Security (EsSalud). MATERIALS AND METHODS: A local guideline development group (local GDG) was established, including specialists in gastroenterology and methodologists. The local GDG formulated 11 clinical questions to be answered by this clinical practice guide (CPG). We searched and selected CPG of UGB published from 2012, which answered the posed questions and obtained a score higher than 60% in domains 1 and 3 of the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. During September 2017, bibliographic searches were conducted in Pubmed, to update 9 clinical questions of the preselected CPGs, and to answer 2 de novo questions. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG reviewed the evidence and formulated the recommendations, points of good clinical practice and the flowchart of evaluation and management, using the GRADE methodology Lastly, the CPG was approved with Resolucion N degrees 80 IETSI-ESSALUD-2017. RESULTS: This CPG addressed 11 clinical questions, divided into four themes: risk assessment, initial management, management of non-variceal UGB, and management of variceal UGB. Based on these questions, 10 recommendations (7 strong recommendations and 3 weak recommendations), 24 points of good clinical practice, and 2 flow charts were formulated. CONCLUSION: This article is the summary of the EsSalud' CPG, where the available scientific evidence on evaluation and management of UGB was evaluated. PMID- 29791431 TI - Pseudo porphyria or porphyria cutanea tarda? PMID- 29791430 TI - Ex vivos models to teaching therapeutic endoscopic ultrasound (T-EUS). AB - BACKGROUND: Endoscopic ultrasound training has a learning curve greater than the other endoscopic therapeutic techniques. One of the preclinical teaching methods is the use of ex vivo porcine models. AIM: To describe five ex vivo porcine models for training in therapeutic echoendoscopic procedures. MATERIALS AND METHODS: Using porcine digestive tract containing esophagus, stomach, duodenum, spleen, liver and gallbladder, five models for therapeutic echoendoscopy training were described. With other segments of the porcine pieces (such as the bladder, spleen segment and omentum segment) and with easily accessible materials (such as grape and ultrasound gel), lesions were simulated to be treated. These models were applied in the Hands on course at the IRCAD (Institut de recherche contre les cancers de l'appareil digestif) Barretos of 2017. Endoscopic equipment and instruments are the same as those used in clinical practice. RESULT: The models are easily reproducible and do not require exchange during the hands on course period. Endoscopic and echographic imaging and tactile sensitivity are similar to the real one. CONCLUSION: The models described in this study demonstrated to be realistic, easy to reproduce and allow repetition during the same session. However, comparative studies are necessary to verify the real impact on teaching. PMID- 29791432 TI - Logistical constraints lead to an intermediate optimum in outbreak response vaccination. AB - Dynamic models in disease ecology have historically evaluated vaccination strategies under the assumption that they are implemented homogeneously in space and time. However, this approach fails to formally account for operational and logistical constraints inherent in the distribution of vaccination to the population at risk. Thus, feedback between the dynamic processes of vaccine distribution and transmission might be overlooked. Here, we present a spatially explicit, stochastic Susceptible-Infected-Recovered-Vaccinated model that highlights the density-dependence and spatial constraints of various diffusive strategies of vaccination during an outbreak. The model integrates an agent-based process of disease spread with a partial differential process of vaccination deployment. We characterize the vaccination response in terms of a diffusion rate that describes the distribution of vaccination to the population at risk from a central location. This generates an explicit trade-off between slow diffusion, which concentrates effort near the central location, and fast diffusion, which spreads a fixed vaccination effort thinly over a large area. We use stochastic simulation to identify the optimum vaccination diffusion rate as a function of population density, interaction scale, transmissibility, and vaccine intensity. Our results show that, conditional on a timely response, the optimal strategy for minimizing outbreak size is to distribute vaccination resource at an intermediate rate: fast enough to outpace the epidemic, but slow enough to achieve local herd immunity. If the response is delayed, however, the optimal strategy for minimizing outbreak size changes to a rapidly diffusive distribution of vaccination effort. The latter may also result in significantly larger outbreaks, thus suggesting a benefit of allocating resources to timely outbreak detection and response. PMID- 29791433 TI - The Belfast Youth Development Study (BYDS): A prospective cohort study of the initiation, persistence and desistance of substance use from adolescence to adulthood in Northern Ireland. AB - BACKGROUND: Substance misuse persists as a major public health issue worldwide with significant costs for society. The development of interventions requires methodologically sound studies to explore substance misuse causes and consequences. This Cohort description paper outlines the design of the Belfast Youth Development (BYDS), one of the largest cohort studies of its kind in the UK. The study was established to address the need for a long-term prospective cohort study to investigate the initiation, persistence and desistance of substance use, alongside life course processes in adolescence and adulthood. The paper provides an overview of BYDS as a longitudinal data source for investigating substance misuse and outlines the study measures, sample retention and characteristics. We also outline how the BYDS data have been used to date and highlight areas ripe for future work by interested researchers. METHODS: The study began in 2000/1 when participants (n = 3,834) were pupils in their first year of post-primary education (age 10/11 years, school year 8) from over 40 schools in Northern Ireland. Children were followed during the school years: Year 9 (in 2002; aged 12; n = 4,343), Year 10 (in 2003; aged 13; n = 4,522), Year 11 (in 2004; aged 14; n = 3,965) and Year 12 (in 2005; aged 15; n = 3,830) and on two more occasions: 2006/07 (aged 16/17; n = 2,335) and 2010/11 (aged 20/21; n = 2,087). Data were collected on substance use, family, schools, neighbourhoods, offending behaviour and mental health. The most novel aspect of the study was the collection of detailed social network data via friendship nominations allowing the investigation of the spread of substance use via friendship networks. In 2004 (school year 11; respondents aged 14), a sub-sample of participants' parents (n = 1,097) and siblings (n = 211) also completed measures on substance use and family dynamics. RESULTS: The most recent wave (in 2010/2011; respondents aged 20/21 years) indicated lifetime use of alcohol, tobacco and cannabis among the cohort was 94, 70 and 45 per cent, respectively. The paper charts the development of drug use behaviour and some of the key results to date are presented. We have also identified a number of key areas ripe for analysis by interested researchers including sexual health and education. CONCLUSIONS: We have established a cohort with detailed data from adolescence to young adulthood, supplemented with parent and sibling reports and peer network data. The dataset, allowing for investigation of trajectories of adolescent substance use, associated factors and subsequent long-term outcomes, constitutes an important resource for longitudinal substance misuse research. A planned further wave as the cohort enter their late twenties and potential to link to administrative data sources, will further enrich the datasets. PMID- 29791434 TI - Food fraud and the perceived integrity of European food imports into China. AB - BACKGROUND/AIMS: Persistent incidents of food fraud in China have resulted in low levels of consumer trust in the authenticity and safety of food that is domestically produced. We examined the relationship between the concerns of Chinese consumers regarding food fraud, and the role that demonstrating authenticity may play in relieving those concerns. METHODS: A two-stage mixed method design research design was adopted. First, qualitative research (focus groups n = 7) was conducted in three Chinese cities, Beijing, Guangzhou and Chengdu to explore concerns held by Chinese consumers in relation to food fraud. A subsequent quantitative survey (n = 850) tested hypotheses derived from the qualitative research and theoretical literature regarding the relationship between attitudinal measures (including risk perceptions, social trust, and perceptions of benefit associated with demonstrating authenticity), and behavioral intention to purchase "authentic" European products using structural equation modelling. RESULTS: Chinese consumers perceive food fraud to be a hazard that represents a food safety risk. Food hazard concern was identified to be geographically influenced. Consumers in Chengdu (tier 2 city) possessed higher levels of hazard concern compared to consumers in Beijing and Guangzhou (tier 1). Structural trust (i.e. trust in actors and the governance of the food supply chain) was not a significant predictor of attitude and intention to purchase authenticated food products. Consumers were shown to have developed 'risk relieving' strategies to compensate for the lack of trust in Chinese food and the dissonance experienced as a consequence of food fraud. Indexical and iconic authenticity cues provided by food manufacturers and regulators were important elements of product evaluations, although geographical differences in their perceived importance were observed. CONCLUSIONS: Targeted communication of authenticity assurance measures, including; regulations; enforcement; product testing; and actions taken by industry may improve Chinese consumer trust in the domestic food supply chain and reduce consumer concerns regarding the food safety risks associated with food fraud. To support product differentiation and retain prestige, European food manufactures operating within the Chinese market should recognise regional disparities in consumer risk perceptions regarding food fraud and the importance of personal risk mitigation strategies adopted by Chinese consumers to support the identification of authentic products. PMID- 29791435 TI - Immunogenicity and efficacy following sequential parenterally-administered doses of Salmonella Enteritidis COPS:FliC glycoconjugates in infant and adult mice. AB - In sub-Saharan Africa, invasive nontyphoidal Salmonella (iNTS) infections with serovars S. Enteritidis, S. Typhimurium and I 4,[5],12:i:- are widespread in children < 5 years old. Development of an efficacious vaccine would provide an important public health tool to prevent iNTS disease in this population. Glycoconjugates of S. Enteritidis core and O-polysaccharide (COPS) coupled to the homologous serovar phase 1 flagellin protein (FliC) were previously shown to be immunogenic and protected adult mice against death following challenge with a virulent Malian S. Enteritidis blood isolate. This study extends these observations to immunization of mice in early life and also assesses protection with partial and full regimens. Anti-COPS and anti-FliC serum IgG titers were assessed in infant and adult mice after immunization with 1, 2 or 3 doses of S. Enteritidis COPS:FliC alone or co-formulated with aluminum hydroxide or monophosphoryl lipid A (MPL) adjuvants. S. Enteritidis COPS:FliC was immunogenic in both age groups, although the immune responses were quantitatively lower in infants. Kinetics of antibody production were similar for the native and adjuvanted formulations after three doses; conjugates formulated with MPL elicited significantly increased anti-COPS IgG titers in adult but not infant mice. Nevertheless, robust protection against S. Enteritidis challenge was seen for all three formulations when three doses were given either during infancy or as adults. We further found that significant protection could be achieved with two COPS:FliC doses, despite elicitation of modest serum anti-COPS IgG antibody titers. These findings guide potential immunization strategies that may be translated to develop a human pediatric iNTS vaccine for sub-Saharan Africa. PMID- 29791437 TI - A randomized controlled trial on the effect of a silver carboxymethylcellulose dressing on surgical site infections after breast cancer surgery. AB - BACKGROUND: The incidence of surgical site infections (SSIs) after breast cancer surgery is relatively high; ranging from 3 to 19%. The role of wound dressings in the prevention of SSI after breast cancer surgery is unclear. This study compares a silver carboxymethylcellulose dressing (AQUACEL Ag Surgical (Aquacel) with standard wound dressing in SSI rate after breast cancer surgery. PATIENTS AND METHODS: A single-centre randomized controlled trial among women >=18 years, diagnosed with breast cancer, undergoing breast conserving or ablative surgery, was conducted in a combined in and outpatient setting. The intervention was the use of Aquacel, compared with standard gauze dressing. Primary outcome measure was SSI following CDC criteria. RESULTS: A total of 230 patients were analysed: 106 in the Aquacel group and 124 controls. Seven patients (6.6%) developed SSI in the Aquacel group and 16 patients (12.9%) in the control group (RR 0.51 [95% Confidence Interval (CI): 0.22-1.20]; p = 0.112; adjusted OR 0.49 [0.19-1.25] p = 0.135)). Unplanned exploratory subgroup analysis of breast conserving surgery patients showed that SSI rate was 1/56 (1.8%) in the Aquacel group vs. 7/65 (10.8%) in controls; adjusted OR 0.15 [0.02-1.31] p = 0.087. The Aquacel group showed better patient satisfaction (median 8 vs. 7 on a Numerical Rating Scale, p = 0.006), fewer dressing changes within 48 hours(adjusted OR 0.12 [0.05-0.27] p<0.001), fewer re-operations (0% vs. 3.2%, p = 0.062), and lower mean wound related treatment costs, both in a high (?265.42 (SD = 908) vs. ?470.65 (SD = 1223) [p<0.001]) and low (?59.12 (SD = 129) vs. ?67.55 (SD = 172) [p<0.001]) attributable costs of SSI model. CONCLUSION: In this randomized controlled trial in women undergoing surgery for breast cancer, the use of AQUACEL Ag Surgical wound dressing did not significantly reduce the occurrence of SSIs compared to standard gauze dressing. The use of Aquacel resulted in significantly improved patient satisfaction, reduced dressing changes and reduced wound-related costs. TRIAL REGISTRATION: www.trialregister.nl: NTR5840. PMID- 29791438 TI - Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens. AB - Identification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized in analysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections. Using the inferred IBD status at genomic locations, we have also developed a novel statistic for identifying loci under positive selection and propose relatedness networks as a means of exploring shared haplotypes within populations. We evaluate the performance of our methodologies for detecting IBD and selection, including comparisons with existing tools, then perform an exploratory analysis of whole genome sequencing data from a global Plasmodium falciparum dataset of more than 2500 genomes. This analysis identifies Southeast Asia as having many highly related isolates, possibly as a result of both reduced transmission from intensified control efforts and population bottlenecks following the emergence of antimalarial drug resistance. Many signals of selection are also identified, most of which overlap genes that are known to be associated with drug resistance, in addition to two novel signals observed in multiple countries that have yet to be explored in detail. Additionally, we investigate relatedness networks over the selected loci and determine that one of these sweeps has spread between continents while the other has arisen independently in different countries. IBD analysis of microorganisms using isoRelate can be used for exploring population structure, positive selection and haplotype distributions, and will be a valuable tool for monitoring disease control and elimination efforts of many diseases. PMID- 29791436 TI - The genomic landscape at a late stage of stickleback speciation: High genomic divergence interspersed by small localized regions of introgression. AB - Speciation is a continuous process and analysis of species pairs at different stages of divergence provides insight into how it unfolds. Previous genomic studies on young species pairs have revealed peaks of divergence and heterogeneous genomic differentiation. Yet less known is how localised peaks of differentiation progress to genome-wide divergence during the later stages of speciation in the presence of persistent gene flow. Spanning the speciation continuum, stickleback species pairs are ideal for investigating how genomic divergence builds up during speciation. However, attention has largely focused on young postglacial species pairs, with little knowledge of the genomic signatures of divergence and introgression in older stickleback systems. The Japanese stickleback species pair, composed of the Pacific Ocean three-spined stickleback (Gasterosteus aculeatus) and the Japan Sea stickleback (G. nipponicus), which co occur in the Japanese islands, is at a late stage of speciation. Divergence likely started well before the end of the last glacial period and crosses between Japan Sea females and Pacific Ocean males result in hybrid male sterility. Here we use coalescent analyses and Approximate Bayesian Computation to show that the two species split approximately 0.68-1 million years ago but that they have continued to exchange genes at a low rate throughout divergence. Population genomic data revealed that, despite gene flow, a high level of genomic differentiation is maintained across the majority of the genome. However, we identified multiple, small regions of introgression, occurring mainly in areas of low recombination rate. Our results demonstrate that a high level of genome-wide divergence can establish in the face of persistent introgression and that gene flow can be localized to small genomic regions at the later stages of speciation with gene flow. PMID- 29791439 TI - Multi-biomarker disease activity score as a predictor of disease relapse in patients with rheumatoid arthritis stopping TNF inhibitor treatment. AB - OBJECTIVE: Successfully stopping or reducing treatment for patients with rheumatoid arthritis (RA) in low disease activity (LDA) may improve cost effectiveness of care. We evaluated the multi-biomarker disease activity (MBDA) score as a predictor of disease relapse after discontinuation of TNF inhibitor (TNFi) treatment. METHODS: 439 RA patients who were randomized to stop TNFi treatment in the POET study were analyzed post-hoc. Three indicators of disease relapse were assessed over 12 months: 1) restarting TNFi treatment, 2) escalation of any DMARD therapy and 3) physician-reported flare. MBDA score was assessed at baseline. Associations between MBDA score and disease relapse were examined using univariate analysis and multivariate logistic regression. RESULTS: At baseline, 50.1%, 35.3% and 14.6% of patients had low (<30), moderate (30-44) or high (>44) MBDA scores. Within 12 months, 49.9% of patients had restarted TNFi medication, 59.0% had escalation of any DMARD and 57.2% had >=1 physician-reported flare. MBDA score was associated with each indicator of relapse. At least one indicator of relapse was observed in 59.5%, 68.4% and 81.3% of patients with low, moderate or high MBDA scores, respectively (P = 0.004). Adjusted for baseline DAS28-ESR, disease duration, BMI and erosions, high MBDA scores were associated with increased risk for restarting TNFi treatment (OR = 1.85, 95% CI 1.00-3.40), DMARD escalation (OR = 1.99, 95% CI 1.01-3.94) and physician-reported flare (OR = 2.00, 95% 1.06-3.77). CONCLUSION: For RA patients with stable LDA who stopped TNFi, a high baseline MBDA score was independently predictive of disease relapse within 12 months. The MBDA score may be useful for identifying patients at risk of relapse after TNFi discontinuation. PMID- 29791440 TI - Cost-effectiveness of dog rabies vaccination programs in East Africa. AB - BACKGROUND: Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost effectiveness of dog rabies vaccination programs in East Africa. METHODS: RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). RESULTS: Without dog vaccination, over 10 years there would a total of be approximately 44,000-65,000 rabid dogs and 2,100-2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000-1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000-1,900 human deaths averted, and cost $404 $305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). CONCLUSIONS: Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs. PMID- 29791441 TI - The impact of young maternal age at birth on neonatal mortality: Evidence from 45 low and middle income countries. AB - OBJECTIVES: This study explores the impact of early motherhood on neonatal mortality, and how this differs between countries and regions. It assesses whether the risk of neonatal mortality is greater for younger adolescent mothers compared with mothers in later adolescence, and explores if differences reflect confounding socio-economic and health care utilisation factors. It also examines how the risks differ for first or subsequent pregnancies. METHODS: The analysis uses 64 Demographic and Health Surveys collected between 2005 and 2015 from 45 countries to explore the relationship between adolescent motherhood (disaggregated as <16 years, 16/17 years and 18/19 years) and neonatal mortality. Both unadjusted bivariate association and logistic regression are used. Regional level multivariate models that adjust for a range of socio-economic, demographic and health service utilisation variables are estimated. Further stratified models are created to examine the excess risk for first and subsequent births separately. FINDINGS: The risk of neonatal mortality in all regions was markedly greater for infants with mothers under 16 years old, although there was marked heterogeneity in patterns between regions. Adjusting for socio-economic, demographic and health service utilisation variables did not markedly change the odds ratios associated with age. The increased risks associated with adolescent motherhood are lowest for first births. CONCLUSION: Our findings particularly highlight the importance of reducing adolescent births among the youngest age group as a strategy for addressing the problem of neonatal mortality, as well ensuring pregnant adolescents have access to quality maternal health services to protect the health of both themselves and their infants. The regional differences in increased risk are a novel finding which requires more exploration. PMID- 29791444 TI - Correction: Solving the influence maximization problem reveals regulatory organization of the yeast cell cycle. AB - [This corrects the article DOI: 10.1371/journal.pcbi.1005591.]. PMID- 29791442 TI - Bacillus cereus, a serious cause of nosocomial infections: Epidemiologic and genetic survey. AB - Bacillus cereus is the 2nd most frequent bacterial agent responsible for food borne outbreaks in France and the 3rd in Europe. In addition, local and systemic infections have been reported, mainly describing individual cases or single hospital setting. The real incidence of such infection is unknown and information on genetic and phenotypic characteristics of the incriminated strains is generally scarce. We performed an extensive study of B. cereus strains isolated from patients and hospital environments from nine hospitals during a 5-year study, giving an overview of the consequences, sources and pathogenic patterns of B. cereus clinical infections. We demonstrated the occurrence of several hospital cross-contaminations. Identical B. cereus strains were recovered from different patients and hospital environments for up to 2 years. We also clearly revealed the occurrence of inter hospital contaminations by the same strain. These cases represent the first documented events of nosocomial epidemy by B. cereus responsible for intra and inter hospitals contaminations. Indeed, contamination of different patients with the same strain of B. cereus was so far never shown. In addition, we propose a scheme for the characterization of B. cereus based on biochemical properties and genetic identification and highlight that main genetic signatures may carry a high pathogenic potential. Moreover, the characterization of antibiotic resistance shows an acquired resistance phenotype for rifampicin. This may provide indication to adjust the antibiotic treatment and care of patients. PMID- 29791443 TI - Traceability, reproducibility and wiki-exploration for "a-la-carte" reconstructions of genome-scale metabolic models. AB - Genome-scale metabolic models have become the tool of choice for the global analysis of microorganism metabolism, and their reconstruction has attained high standards of quality and reliability. Improvements in this area have been accompanied by the development of some major platforms and databases, and an explosion of individual bioinformatics methods. Consequently, many recent models result from "a la carte" pipelines, combining the use of platforms, individual tools and biological expertise to enhance the quality of the reconstruction. Although very useful, introducing heterogeneous tools, that hardly interact with each other, causes loss of traceability and reproducibility in the reconstruction process. This represents a real obstacle, especially when considering less studied species whose metabolic reconstruction can greatly benefit from the comparison to good quality models of related organisms. This work proposes an adaptable workspace, AuReMe, for sustainable reconstructions or improvements of genome-scale metabolic models involving personalized pipelines. At each step, relevant information related to the modifications brought to the model by a method is stored. This ensures that the process is reproducible and documented regardless of the combination of tools used. Additionally, the workspace establishes a way to browse metabolic models and their metadata through the automatic generation of ad-hoc local wikis dedicated to monitoring and facilitating the process of reconstruction. AuReMe supports exploration and semantic query based on RDF databases. We illustrate how this workspace allowed handling, in an integrated way, the metabolic reconstructions of non-model organisms such as an extremophile bacterium or eukaryote algae. Among relevant applications, the latter reconstruction led to putative evolutionary insights of a metabolic pathway. PMID- 29791445 TI - The search for instantaneous vection: An oscillating visual prime reduces vection onset latency. AB - Typically it takes up to 10 seconds or more to induce a visual illusion of self motion ("vection"). However, for this vection to be most useful in virtual reality and vehicle simulation, it needs to be induced quickly, if not immediately. This study examined whether vection onset latency could be reduced towards zero using visual display manipulations alone. In the main experiments, visual self-motion simulations were presented to observers via either a large external display or a head-mounted display (HMD). Priming observers with visually simulated viewpoint oscillation for just ten seconds before the main self-motion display was found to markedly reduce vection onset latencies (and also increase ratings of vection strength) in both experiments. As in earlier studies, incorporating this simulated viewpoint oscillation into the self-motion displays themselves was also found to improve vection. Average onset latencies were reduced from 8-9s in the no oscillating control condition to as little as 4.6 s (for external displays) or 1.7 s (for HMDs) in the combined oscillation condition (when both the visual prime and the main self-motion display were oscillating). As these display manipulations did not appear to increase the likelihood or severity of motion sickness in the current study, they could possibly be used to enhance computer generated simulation experiences and training in the future, at no additional cost. PMID- 29791446 TI - Nitrogen limitation, toxin synthesis potential, and toxicity of cyanobacterial populations in Lake Okeechobee and the St. Lucie River Estuary, Florida, during the 2016 state of emergency event. AB - Lake Okeechobee, FL, USA, has been subjected to intensifying cyanobacterial blooms that can spread to the adjacent St. Lucie River and Estuary via natural and anthropogenically-induced flooding events. In July 2016, a large, toxic cyanobacterial bloom occurred in Lake Okeechobee and throughout the St. Lucie River and Estuary, leading Florida to declare a state of emergency. This study reports on measurements and nutrient amendment experiments performed in this freshwater-estuarine ecosystem (salinity 0-25 PSU) during and after the bloom. In July, all sites along the bloom exhibited dissolved inorganic nitrogen-to phosphorus ratios < 6, while Microcystis dominated (> 95%) phytoplankton inventories from the lake to the central part of the estuary. Chlorophyll a and microcystin concentrations peaked (100 and 34 MUg L-1, respectively) within Lake Okeechobee and decreased eastwards. Metagenomic analyses indicated that genes associated with the production of microcystin (mcyE) and the algal neurotoxin saxitoxin (sxtA) originated from Microcystis and multiple diazotrophic genera, respectively. There were highly significant correlations between levels of total nitrogen, microcystin, and microcystin synthesis gene abundance across all surveyed sites (p < 0.001), suggesting high levels of nitrogen supported the production of microcystin during this event. Consistent with this, experiments performed with low salinity water from the St. Lucie River during the event indicated that algal biomass was nitrogen-limited. In the fall, densities of Microcystis and concentrations of microcystin were significantly lower, green algae co-dominated with cyanobacteria, and multiple algal groups displayed nitrogen-limitation. These results indicate that monitoring and regulatory strategies in Lake Okeechobee and the St. Lucie River and Estuary should consider managing loads of nitrogen to control future algal and microcystin-producing cyanobacterial blooms. PMID- 29791447 TI - Development of an RP-UHPLC-PDA method for quantification of free gossypol in cottonseed cake and fungal-treated cottonseed cake. AB - Cottonseed cake biomass, which is a residue of oil extraction, is potentially appropriate for use as animal feed, given the high mineral, fibre and protein content. The presence of free gossypol, however, a toxic pigment in the glands of the cotton plant, limits use of this biomass for monogastric livestock. A promising method to detoxify cottonseed cake relies on fermentation by fungi, which can eliminate up to 100% of gossypol. In order to quantify trace levels of free gossypol in different cotton materials, including cottonseed cake treated with macrofungi, a simple and rapid chromatographic detection method was developed and validated. Under optimized conditions, extraction was performed using 70% acetone. The extract was then analysed by Ultra High-Performance Liquid Chromatography (UHPLC), with gradient elution on a C18 reverse phase column KINETEX(r) (100 x 2.10 mm, 2.6 MUm). Methanol-0.1% TFA aqueous solution was employed as mobile phase and PDA detection conducted at 254 nm. The optimized method was validated by analysis of specificity, linearity and range, limit of detection, limit of quantification, precision and accuracy. Detection and quantification limits were observed at 0.2 and 0.5 MUg/mL, respectively. With good reproducibility, with precision (RSD)<10% and recovery greater than 94%, the developed assay was appropriate for quantification of low quantities of free gossypol. The validated method was successfully applied to determine trace levels of free gossypol cottonseed treated with a macrofungus. PMID- 29791448 TI - Abundance and distribution of microplastics within surface sediments of a key shellfish growing region of Canada. AB - The abundance and distribution of microplastics within 5 sediment size classes (>5000 MUm, 1000-5000 MUm, 250-1000 MUm, 250-0.63 MUm and < 0.63 MUm) were determined for 16 sites within Lambert Channel and Baynes Sound, British Columbia, Canada. This region is Canada's premier growing area for the Pacific oyster (Crassostrea gigas). Microplastics were found at all sampling locations indicating widespread contamination of this region with these particles. Three types of microplastics were recovered: microbeads, which occurred in the greatest number (up to 25000/kg dry sediment) and microfibers and microfragments, which were much less in number compared with microbeads and occurred in similar amounts (100-300/kg dry sediment). Microbeads were recovered primarily in the < 0.63 MUm and 250-0.63 MUm sediment size class, whereas microfragments and microfibers were generally identified in all 5 sediment size classes. Abundance and distribution of the three types of microplastics were spatially dependent with principal component analysis (PCA) indicating that 84 percent of the variation in abundance and distribution was due to the presence of high numbers of microbeads at three locations within the study region. At these sites, microbeads expressed as a percent component of the sediment by weight was similar to key geochemical components that govern trace metal behavior and availability to benthic organisms. Microbeads have been shown to accumulate metals from the aquatic environment, hence in addition to the traditional geochemical components such as silt and organic matter, microplastics also need to be considered as a sediment component that can influence trace metal geochemistry. Our findings have shown that BC's premier oyster growing region is highly contaminated with microplastics, notably microbeads. It would be prudent to assess the degree to which oysters from this region are ingesting microplastics. If so, it would have direct implications for Canada's oyster farming industry with respect to the health of the oyster and the quality of product that is being farmed and sets an example for other shellfish growing regions of the world. PMID- 29791449 TI - Impact of involvement of non-formal health providers on TB case notification among migrant slum-dwelling populations in Odisha, India. AB - BACKGROUND: Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from "friendly neighbourhood" non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. METHODS: Adopting a quasi experimental before-after design, four RNTCP units from two major urban industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population. RESULTS: The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p<0.001) cases. The increase was immediate, evident from the rise in level in the time series analysis by 50.42(10.28, 90.55; p = 0.02) cases. CONCLUSION: Engagement with NFHPs contributed to an increase in TB notification to RNTCP from key under reached, slum-dwelling migrant populations. PMID- 29791450 TI - Significant acceleration of emergency response using smartphone geolocation data and a worldwide emergency call support system. AB - IMPORTANCE: When patients are disorientated or experience language barriers, it is impossible to activate the emergency response system. In these cases, the delay for receiving appropriate help can extend to several hours. OBJECTIVES: A worldwide emergency call support system (ECSS), including geolocation of modern smartphones (GPS, WLAN and LBS), was established referring to E911 and eCall systems. The system was tested for relevance in quickly forwarding abroad emergency calls to emergency medical services (EMS). DESIGN: To verify that geolocation data from smartphones are exact enough to be used for emergency cases, the accuracy of GPS (global positioning system), Wi-Fi (wireless LAN network) and LBS (location based system) was tested in eleven different countries and compared to actual location. The main objective was analyzed by simulation of emergencies in different countries. The time delay in receiving help in unsuccessful emergency call cases by using the worldwide emergency call support system (ECSS) was measured. RESULTS: GPS is the gold standard to locate patients with an average accuracy of 2.0 +/- 3.3 m. Wi-Fi can be used within buildings with an accuracy of 7.0 +/- 24.1 m. Using ECSS, the emergency call leads to a successful activation of EMS in 22.8 +/- 10.8 min (Median 21 min). The use of a simple app with one button to touch did never cause any delay. CONCLUSIONS AND RELEVANCE: The worldwide emergency call support system (ECSS) significantly improves the emergency response in cases of disorientated patients or language barriers. Under circumstances without ECSS, help can be delayed by 2 or more hours and might have relevant lifesaving effects. This is the first time that Wi Fi geolocation could prove to be a useful improvement in emergencies to enhance GPS, especially within or close to buildings. PMID- 29791451 TI - Exploring adverse parent-child relationships from the perspective of convicted child murderers: A South African qualitative study. AB - Child homicide is the most extreme form of violence against children. Within South Africa, children face the highest risk of homicide by parents/caregivers. It is suggested that prolonged exposure to adverse relationships with one's own parents may be linked to committing child homicide as it may lead to psychological damage and disturb neurological functioning. This paper explores the adverse parent-child relationships of 22 men and women incarcerated for the murder of either a biological child, a stepchild or a child in their care and draws on 49 in-depth interviews with these participants. We illustrate that traumatic parent-child experiences in the form of absent parents, neglect and abuse have a profound impact on establishing unhealthy attachment styles and emphasize the importance of early adverse parent-child bonds in setting the tone for future bonds as adults. The pathway to adopting an adverse attachment with one's own child is argued to be influenced by these early traumatic emotional experiences within the home. This study highlights the need to acknowledge the impact that adverse parent-child experiences have on the formation of violent forms of parental behavior. It is imperative to reduce children's emotional vulnerabilities by implementing strategies to strengthen current parenting practices, to promote the development of less violent parent-child relationships and to work towards resolving parents' experiences of trauma in reducing child homicide. PMID- 29791452 TI - Validity and reliability of two alternate versions of the Montreal Cognitive Assessment (Hong Kong version) for screening of Mild Neurocognitive Disorder. AB - OBJECTIVE: Repeated testing using the Montreal Cognitive Assessment (MoCA) increases risks for practice effects which may bias measurements of cognitive change. The objective of this study is to develop two alternate versions of the MoCA (Hong Kong version; HK-MoCA) and to investigate the validity and reliability of the alternate versions in patients with DSM-5 Mild Neurocognitive Disorder (Mild NCD) and cognitively healthy controls. METHODS: Concurrent validity and inter-scale agreement were examined by Pearson correlation of the total scores between the original and alternate versions and the Bland-Altman Method. Criterion validity of the two alternate versions in differentiating patients with Mild NCD was tested using receiver operating characteristic curve (ROC) analysis. One-month test-retest and inter-rater reliability were examined in 20 participants. Internal consistency of the alternate versions was measured by the Cronbach's alpha. RESULTS: 30 controls (age 73.4 [4.5] years, 60% female) and 30 patients (age 75.4 [5.5] years, 73% female) with Mild NCD were recruited. Both alternate versions significantly correlated with the original version (r = 0.79 0.87, p<0.001). Mean differences of 0.17 and -0.40 points were found between the total scores of the alternate with the original versions with a consistent level of agreement observed throughout the range of cognitive abilities. Both alternate versions significantly differentiated patients with Mild NCD from healthy controls (area under ROC 0.922 and 0.724, p<0.001) and showed good one-month test retest reliability (intra-class correlation [ICC] = 0.92 and 0.82) and inter rater reliability (ICC = 0.99 and 0.87) and high internal consistency (Cronbach alpha = 0.79 and 0.75). CONCLUSION: The two alternate versions of the HK-MoCA are useful for Mild NCD screening. PMID- 29791453 TI - The association between food insecurity and incident type 2 diabetes in Canada: A population-based cohort study. AB - BACKGROUND: A pervasive and persistent finding is the health disadvantage experienced by those in food insecure households. While clear associations have been identified between food insecurity and diabetes risk factors, less is known about the relationship between food insecurity and incident type 2 diabetes. The objective of this study is to investigate the association between household food insecurity and the future development of type 2 diabetes. METHODS: We used data from Ontario adult respondents to the 2004 Canadian Community Health Survey, linked to health administrative data (n = 4,739). Food insecurity was assessed with the Household Food Security Survey Module and incident type 2 diabetes cases were identified by the Ontario Diabetes Database. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type 2 diabetes as a function of food insecurity. RESULTS: Canadians in food insecure households had more than 2 times the risk of developing type 2 diabetes compared to those in food secure households [HR = 2.40, 95% CI = 1.17-4.94]. Additional adjustment for BMI attenuated the association between food insecurity and type 2 diabetes [HR = 2.08, 95% CI = 0.99, 4.36]. CONCLUSIONS: Our findings indicate that food insecurity is independently associated with increased diabetes risk, even after adjustment for a broad set of measured confounders. Examining diabetes risk from a broader perspective, including a comprehensive understanding of socioeconomic and biological pathways is paramount for informing policies and interventions aimed at mitigating the future burden of type 2 diabetes. PMID- 29791454 TI - Development and validation of a short food questionnaire to screen for low protein intake in community-dwelling older adults: The Protein Screener 55+ (Pro55+). AB - In old age, sufficient protein intake is important to preserve muscle mass and function. Around 50% of older adults (65+ y) consumes <=1.0 g/kg adjusted body weight (BW)/day (d). There is no rapid method available to screen for low protein intake in old age. Therefore, we aimed to develop and validate a short food questionnaire to screen for low protein intake in community-dwelling older adults. We used data of 1348 older men and women (56-101 y) of the LASA study (the Netherlands) to develop the questionnaire and data of 563 older men and women (55-71 y) of the HELIUS study (the Netherlands) for external validation. In both samples, protein intake was measured by the 238-item semi-quantitative HELIUS food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to predict protein intake <=1.0 g/kg adjusted BW/d (based on the HELIUS FFQ). Candidate predictor variables were FFQ questions on frequency and amount of intake of specific foods. In both samples, 30% had a protein intake <=1.0 g/kg adjusted BW/d. Our final model included adjusted body weight and 10 questions on the consumption (amount on average day or frequency in 4 weeks) of: slices of bread (number); glasses of milk (number); meat with warm meal (portion size); cheese (amount and frequency); dairy products (like yoghurt) (frequency); egg(s) (frequency); pasta/noodles (frequency); fish (frequency); and nuts/peanuts (frequency). The area under the receiver operating characteristic curve (AUC) was 0.889 (95% CI 0.870-0.907). The calibration slope was 1.03 (optimal slope 1.00). At a cut-off of <=0.8 g/kg adjusted BW/d, the AUC was 0.916 (96% CI 0.897-0.936). Applying the regression equation to the HELIUS sample, the AUC was 0.856 (95% CI 0.824-0.888) and the calibration slope 0.92. Regression coefficients were therefore subsequently shrunken by a linear factor 0.92. To conclude, the short food questionnaire (Pro55+) can be used to validly screen for protein intake <=1.0 g/kg adjusted BW/d in community-dwelling older adults. An online version can be found at www.proteinscreener.nl. External validation in other countries is recommended. PMID- 29791455 TI - National patterns of physician management of sleep apnea and treatment among patients with hypertension. AB - STUDY OBJECTIVES: Sleep apnea is associated with hypertension, and treatment may improve outcomes. We examine national burden of sleep apnea, rates of sleep apnea treatment, and whether racial/ethnic disparities exist among patients with hypertension. METHODS: Data from the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS), 2005 2012, were analyzed (N = 417,950). We identified hypertension patient visits where sleep apnea diagnosis or complaint was recorded. Primary outcome measures were sleep study, medication, or behavioral therapy (diet, weight loss, or exercise counseling). We used multivariate logistic regression to examine treatment by demographic/clinical factors. RESULTS: Among patients with hypertension, sleep apnea was identified in 11.2-per-1,000 visits. Overall, patients with hypertension and a sleep disorder were referred for sleep study in 14.4% of visits, prescribed sleep medication in 11.2% of visits, and offered behavioral therapy in 34.8% of visits. Adjusted analyses show behavioral therapy more likely to be provided to obese patients than normal/overweight (OR = 4.96, 95%CI[2.93-8.38]), but less likely to be provided to smokers than nonsmokers (OR = 0.54, 95%CI[0.32-0.93]). Non-Hispanic blacks were less likely to receive medications than non-Hispanic whites (OR = 0.19, 95% CI[0.06-0.65]). CONCLUSIONS: In the U.S., sleep apnea were observed in a small proportion of hypertension visits, a population at high-risk for the disorder. One explanation for the low prevalence of sleep apnea observed in this patient population at high risk for the disorder is under-diagnosis of sleep related breathing disorders. Behavioral therapy was underutilized, and non-Hispanic Blacks were less likely to receive medications than non-Hispanic Whites. PMID- 29791457 TI - A feasibility study of colorectal cancer diagnosis via circulating tumor DNA derived CNV detection. AB - Circulating tumor DNA (ctDNA) has shown great promise as a biomarker for early detection of cancer. However, due to the low abundance of ctDNA, especially at early stages, it is hard to detect at high accuracies while keeping sequencing costs low. Here we present a pilot stage study to detect large scale somatic copy numbers variations (CNVs), which contribute more molecules to ctDNA signal compared to point mutations, via cell free DNA sequencing. We show that it is possible to detect somatic CNVs in early stage colorectal cancer (CRC) patients and subsequently discriminate them from normal patients. With 25 normal and 24 CRC samples, we achieve 100% specificity (lower bound confidence interval: 86%) and ~79% sensitivity (95% confidence interval: 63% - 95%,), though the performance should be considered with caution given the limited sample size. We report a lack of concordance between the CNVs detected via cfDNA sequencing and CNVs identified in parent tissue samples. However, recent findings suggest that a lack of concordance is expected for CNVs in CRC because of their sub-clonal nature. Finally, the CNVs we detect very likely contribute to cancer progression as they lie in functionally important regions, and have been shown to be associated with CRC specifically. This study paves the path for a larger scale exploration of the potential of CNV detection for both diagnoses and prognoses of cancer. PMID- 29791456 TI - Multi-species suppression of herbivores through consumptive and non-consumptive effects. AB - Most studies investigating the importance of non-consumptive interactions for herbivore suppression focus on pairwise interactions between one predator and one prey, ignoring any community context. Further, the potential for non-consumptive interactions to arise between herbivores and non-enemy organisms is commonly overlooked. We investigated the relative contributions of consumptive and non consumptive effects to aphid suppression by a wasp assemblage containing both enemies and non-enemies. We examined the suppression of two aphid species with different defensive strategies, pea aphids (Acyrthosiphon pisum), which drop from their host plant to the ground, and green peach aphids (Myzus persicae), which remain on the plant and merely walk away. The expectation was that riskier defensive behaviors, like abandoning the plant, would result in larger non consumptive effects. We found that the outcome of multi-species interactions differed depending on the mechanism of suppression, with interference among wasps in their consumptive effects and additivity in their non-consumptive effects. We also found that, despite differences in defensive strategies, the non-consumptive effects of wasps on aphid abundance were significant for both aphid species. Furthermore, when part of a multi-species assemblage, non-enemies enhanced aphid suppression via complementary non-consumptive effects with lethal enemies, but this increase in suppression was offset by disruption in the consumptive suppression of aphids by lethal enemies. We conclude that non-consumptive effects arise from interactions with both enemy and non-enemy species and that both can contribute to herbivore suppression when part of a broader community. We predict that encouraging the presence of non-enemy organisms may provide insurance against fluctuations in the size of consumptive enemy populations and buffer against herbivore outbreaks. PMID- 29791458 TI - Incidence of lung cancer histologic cell-types according to neighborhood factors: A population based study in California. AB - BACKGROUND: The relationships between neighborhood factors (i.e., neighborhood socioeconomic status (nSES) and ethnic enclave) and histologic subtypes of lung cancer for racial/ethnic groups, particularly Hispanics and Asian American/Pacific Islanders (AAPIs), are poorly understood. METHODS: We conducted a population-based study of 75,631 Californians diagnosed with lung cancer from 2008 through2012. We report incidence rate ratios (IRRs) for lung cancer histologic cell-types by nSES among racial/ethnic groups (non-Hispanic (NH) Whites, NH Blacks, Hispanics and AAPIs) and according to Hispanic or Asian neighborhood ethnic enclave status among Hispanics and AAPIs, respectively. In addition, we examined incidence jointly by nSES and ethnic enclave. RESULTS: Patterns of lung cancer incidence by nSES and ethnic enclave differed across race/ethnicity, sex, and histologic cell-type. For adenocarcinoma, Hispanic males and females, residing in both low nSES and high nSES neighborhoods that were low enclave, had higher incidence rates compared to those residing in low nSES, high enclave neighborhoods; males (IRR, 1.17 [95% CI, 1.04-1.32] and IRR, 1.15 [95% CI, 1.02-1.29], respectively) and females (IRR, 1.29 [95% CI, 1.15-1.44] and IRR, 1.51 [95% CI, 1.36-1.67], respectively). However, AAPI males residing in both low and high SES neighborhoods that were also low enclave had lower adenocarcinoma incidence. CONCLUSIONS: Neighborhood factors differentially influence the incidence of lung cancer histologic cell-types with heterogeneity in these associations by race/ethnicity and sex. For Hispanic males and females and AAPI males, neighborhood ethnic enclave status is strongly associated with lung adenocarcinoma incidence. PMID- 29791459 TI - Species identification and connectivity of marine amphipods in Canada's three oceans. AB - Monitoring the distribution of marine biodiversity is a crucial step to better assess the impacts of global changes. Arctic marine fauna is dominated by amphipods in terms of abundance and biomass. These peracarids are an important marine order of crustaceans but the number of species found in the different Canadian oceans is currently unknown. Furthermore, most species are difficult to identify due to poor taxonomic descriptions and morphological convergence. The aim of this study was to assess the species diversity of marine amphipods in the three Canadian oceans using DNA barcoding. To do so, we produced a database of DNA barcodes of amphipods from the three Canadian Oceans publicly available from the BOLD website to which we added 310 new sequences from the Canadian Arctic Archipelago. We first delimited amphipod species based on barcode gap detection techniques and tree based method (bPTP) and then compared the composition of amphipods among the three oceans in order to assess the influence of past transarctic exchanges on Arctic diversity. Our analysis of 2309 sequences which represent more than 250 provisional species revealed a high connectivity between the Atlantic and Arctic Oceans. Our results also suggest that a single threshold to delimitate species is not suitable for amphipods. This study highlights the challenges involved in species delimitation and the need to obtain complete barcoding inventories in marine invertebrates. PMID- 29791460 TI - Are saving appearance responses typical communication patterns in Alzheimer's disease? AB - INTRODUCTION: To keep up appearances, people with dementia sometimes pretend to know the correct answer, as seen during administration of neuropsychological tests such as the Mini-Mental State Examination (MMSE). These saving appearance responses (SARs) of people with dementia often lead to caregivers and/or medical staff underestimating the severity of dementia and impede proper early initiation of treatment. However, most descriptions of SARs are based on empirical knowledge of clinicians. In this study, we investigated whether SARs are typical communication patterns in people with Alzheimer's disease (AD), compared with mild cognitive impairment (MCI) or dementia with Lewy bodies (DLB). METHODS: The participants were 107 outpatients with AD, 16 with mixed AD with cerebrovascular dementia, 55 with MCI, and 30 with DLB. We assessed the occurrence of SARs during the MMSE. The relationships between the SARs and AD were examined by the chi2 test and logistic regression analysis. RESULTS: People with AD who showed SARs were 57.9%, whereas those with MCI were 18.2% and DLB were 20.0% (P with Bonferroni correction < 0.05). Although there were significant differences in some variables in each group of diagnosis, logistic regression analysis showed that people with AD were more likely to show SARs than those with MCI (Odds ratio = 3.48, 95% Confidential Interval = 1.18-10.28) and DLB (Odds ratio = 4.24, 95% Confidential Interval = 1.50-12.01), even after controlling for sex, estimated disease duration, MMSE, and frontal assessment battery scores. CONCLUSION: The occurrence of SARs could be found most frequently in people with AD. Clinicians should develop a respectful attitude toward dementia patients with SARs because SARs imply conflicted feelings about questions that patients cannot answer correctly. PMID- 29791461 TI - A discrete mathematical model for the aggregation of beta-Amyloid. AB - Dementia associated with the Alzheimer's disease is thought to be correlated with the conversion of the beta - Amyloid (Abeta) peptides from soluble monomers to aggregated oligomers and insoluble fibrils. We present a discrete-time mathematical model for the aggregation of Abeta monomers into oligomers using concepts from chemical kinetics and population dynamics. Conditions for the stability and instability of the equilibria of the model are established. A formula for the number of monomers that is required for producing oligomers is also given. This may provide compound designers a mechanism to inhibit the Abeta aggregation. PMID- 29791462 TI - Using within-day hive weight changes to measure environmental effects on honey bee colonies. AB - Patterns in within-day hive weight data from two independent datasets in Arizona and California were modeled using piecewise regression, and analyzed with respect to honey bee colony behavior and landscape effects. The regression analysis yielded information on the start and finish of a colony's daily activity cycle, hive weight change at night, hive weight loss due to departing foragers and weight gain due to returning foragers. Assumptions about the meaning of the timing and size of the morning weight changes were tested in a third study by delaying the forager departure times from one to three hours using screen entrance gates. A regression of planned vs. observed departure delays showed that the initial hive weight loss around dawn was largely due to foragers. In a similar experiment in Australia, hive weight loss due to departing foragers in the morning was correlated with net bee traffic (difference between the number of departing bees and the number of arriving bees) and from those data the payload of the arriving bees was estimated to be 0.02 g. The piecewise regression approach was then used to analyze a fifth study involving hives with and without access to natural forage. The analysis showed that, during a commercial pollination event, hives with previous access to forage had a significantly higher rate of weight gain as the foragers returned in the afternoon, and, in the weeks after the pollination event, a significantly higher rate of weight loss in the morning, as foragers departed. This combination of continuous weight data and piecewise regression proved effective in detecting treatment differences in foraging activity that other methods failed to detect. PMID- 29791463 TI - Recurrent spatio-temporal modeling of check-ins in location-based social networks. AB - Social networks are getting closer to our real physical world. People share the exact location and time of their check-ins and are influenced by their friends. Modeling the spatio-temporal behavior of users in social networks is of great importance for predicting the future behavior of users, controlling the users' movements, and finding the latent influence network. It is observed that users have periodic patterns in their movements. Also, they are influenced by the locations that their close friends recently visited. Leveraging these two observations, we propose a probabilistic model based on a doubly stochastic point process with a periodic-decaying kernel for the time of check-ins and a time varying multinomial distribution for the location of check-ins of users in the location-based social networks. We learn the model parameters by using an efficient EM algorithm, which distributes over the users, and has a linear time complexity. Experiments on synthetic and real data gathered from Foursquare show that the proposed inference algorithm learns the parameters efficiently and our method models the real data better than other alternatives. PMID- 29791464 TI - The influence of increased distal loading on metabolic cost, efficiency, and kinematics of roller ski skating. AB - The purpose of the present study was to examine the influence of increased loading of the roller ski on metabolic cost, gross efficiency, and kinematics of roller ski skating in steep and moderate terrain, while employing two incline specific techniques. Ten nationally ranked male cross-country skiers were subjected to four 7-minute submaximal intervals, with 0, 0.5, 1.0, and 1.5 kg added beneath the roller-ski in a randomized order. This was done on two separate days, with the G2 skating at 12% incline and 7 km/h speed and G3 skating at 5% incline and 14 km/h speed, respectively. At 12% incline, there was a significant increase in metabolic rate and a decrease in gross efficiency with added weight (P<0.001 and P = 0.002). At 5% incline, no change in metabolic rate or gross efficiency was found (P = 0.89 and P = 0.11). Rating of perceived exertion (RPE) increased gradually with added weight at both inclines (P>0.05). No changes in cycle characteristics were observed between the different ski loadings at either incline, although the lateral and vertical displacements of the foot/skis were slightly altered at 12% incline with added weight. In conclusion, the present study demonstrates that increased loading of the ski increases the metabolic cost and reduces gross efficiency during steep uphill roller skiing in G2 skating, whereas no significant effect was revealed when skating on relatively flat terrain in G3. Cycle characteristics remained unchanged across conditions at both inclines, whereas small adjustments in the displacement of the foot coincided with the efficiency changes in uphill terrain. The increased RPE values with added ski-weight at both inclines indicates that other factors than those measured here could have influenced effort and/or fatigue when lifting a heavier ski. PMID- 29791466 TI - Understanding health advocacy in family medicine and psychiatry curricula and practice: A qualitative study. AB - BACKGROUND: We explored understanding and experiences of health advocacy among psychiatry and family medicine residents and faculty and the implications for clinical care and teaching through the lens of relationship-centred care. METHODS: This qualitative study was conducted in the psychiatry and family medicine departments at a large urban university. We interviewed 19 faculty members and conducted two focus groups with 18 residents. Semi-structured questions explored the relational meaning of health advocacy, how residents and faculty learned about the role and ethical considerations involved in incorporating advocacy work into clinical practice within a relationship-centred care framework. RESULTS: Four themes emerged from the interviews and focus groups: 1) health advocacy as an extension of the relationship to self; 2) health advocacy and professional boundaries in the physician-patient relationship; 3) health advocacy within a team-based approach; and 4) health advocacy and the physician-community/organization relationship. Participants described implications for practice of the challenges of health advocacy, including perceived institutional risks, professional boundaries and the appropriation of patient voice. CONCLUSIONS: Our study provides insights into the relational complexities of the health advocate role in residency curriculum and clinical practice. All participants described health advocacy as a broad spectrum of actions that are guided by relationships among patients, health care professionals and communities. Our analysis revealed that some challenges that participants identified with a health advocacy role could be addressed by anchoring the role within a specific theoretical framework. This would better enable us to create a culture of advocacy in the training and development of physicians. PMID- 29791465 TI - Predictors of subclinical carotid atherosclerosis in middle-aged women. AB - BACKGROUND: Traditional strategies for primary cardiovascular prevention have been insufficient in reducing the high rates of coronary ischemic events in women, probably because these women are often stratified into low-risk groups. However, cardiovascular diseases continue to be the main cause of morbidity and mortality in women worldwide. We hypothesized that carotid atherosclerosis (CA) is common in middle-aged women. METHODS: We prospectively evaluated asymptomatic peri- and post-menopausal women with no cardiovascular diseases or the use of hormone therapy from two gynecologic clinics. All the patients underwent full clinical and laboratory evaluation and underwent a B-mode ultrasound for carotid evaluations. The presence of CA was defined as the presence of plaque and/or carotid intima-media thickness (CIMT)>1.00 mm. We performed logistic regression to evaluate independent predictors of CA. RESULTS: We studied 823 women (age: 54.4+/-5.4 years; body mass index-BMI: 28.5+/-4.9 kg/m2; diabetes:10%; hypertension: 58%). The prevalence of CA was 12.7% for the entire population and 11% for the low-risk sub-group as defined by a Framingham risk score <5%. In the multivariate model, age: odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.25-1.89,p<0.001; current smoker status: OR = 2.69, 95% CI = 1.48-4.91, p = 0.001; total cholesterol: OR = 1.13, 95% CI = 1.03-1.24, p = 0.008; and systolic blood pressure: OR = 1.01, 95% CI = 1.00-1.02, p = 0.030 remained independently associated with CA. CONCLUSION: Subclinical CA is common among asymptomatic middle-aged women, and traditional risk factors are independently associated with CA. These findings are particularly relevant for improving cardiovascular health in women. PMID- 29791468 TI - Do altmetrics correlate with the quality of papers? A large-scale empirical study based on F1000Prime data. AB - In this study, we address the question whether (and to what extent, respectively) altmetrics are related to the scientific quality of papers (as measured by peer assessments). Only a few studies have previously investigated the relationship between altmetrics and assessments by peers. In the first step, we analyse the underlying dimensions of measurement for traditional metrics (citation counts) and altmetrics-by using principal component analysis (PCA) and factor analysis (FA). In the second step, we test the relationship between the dimensions and quality of papers (as measured by the post-publication peer-review system of F1000Prime assessments)-using regression analysis. The results of the PCA and FA show that altmetrics operate along different dimensions, whereas Mendeley counts are related to citation counts, and tweets form a separate dimension. The results of the regression analysis indicate that citation-based metrics and readership counts are significantly more related to quality, than tweets. This result on the one hand questions the use of Twitter counts for research evaluation purposes and on the other hand indicates potential use of Mendeley reader counts. PMID- 29791467 TI - Scan patterns during scene viewing predict individual differences in clinical traits in a normative sample. AB - The relationship between viewer individual differences and gaze control has been largely neglected in the scene perception literature. Recently we have shown a robust association between individual differences in viewer cognitive capacity and scan patterns during scene viewing. These findings suggest other viewer individual differences may also be associated with scene gaze control. Here we expand our findings to quantify the relationship between individual differences in clinical traits and scene viewing behavior in a normative sample. The present study used Successor Representation Scanpath Analysis (SRSA) to quantify the strength of the association between individual differences in scan patterns during real-world scene viewing and individual differences in viewer attention deficit disorder, autism spectrum disorder, and dyslexia scores. The SRSA results revealed individual differences in vertical scan patterns that explained more than half of the variance in attention-deficit scores, a third of the variance in autism quotient scores, and about a quarter of the variance in dyslexia scores. These results suggest that individual differences in attention-deficit disorder, autism spectrum disorder, and dyslexia scores are most strongly associated with vertical scanning behaviors when viewing real-world scenes. More importantly, our results suggest scene scan patterns have promise as potential diagnostic tools and provide insight into the types of vertical scan patterns that are most diagnostic. PMID- 29791469 TI - Ffuzz: Towards full system high coverage fuzz testing on binary executables. AB - Bugs and vulnerabilities in binary executables threaten cyber security. Current discovery methods, like fuzz testing, symbolic execution and manual analysis, both have advantages and disadvantages when exercising the deeper code area in binary executables to find more bugs. In this paper, we designed and implemented a hybrid automatic bug finding tool-Ffuzz-on top of fuzz testing and selective symbolic execution. It targets full system software stack testing including both the user space and kernel space. Combining these two mainstream techniques enables us to achieve higher coverage and avoid getting stuck both in fuzz testing and symbolic execution. We also proposed two key optimizations to improve the efficiency of full system testing. We evaluated the efficiency and effectiveness of our method on real-world binary software and 844 memory corruption vulnerable programs in the Juliet test suite. The results show that Ffuzz can discover software bugs in the full system software stack effectively and efficiently. PMID- 29791470 TI - Quality of community basic medical service utilization in urban and suburban areas in Shanghai from 2009 to 2014. AB - Urban areas usually display better health care services than rural areas, but data about suburban areas in China are lacking. Hence, this cross-sectional study compared the utilization of community basic medical services in Shanghai urban and suburban areas between 2009 and 2014. These data were used to improve the efficiency of community health service utilization and to provide a reference for solving the main health problems of the residents in urban and suburban areas of Shanghai. Using a two-stage random sampling method, questionnaires were completed by 73 community health service centers that were randomly selected from six districts that were also randomly selected from 17 counties in Shanghai. Descriptive statistics, principal component analysis, and forecast analysis were used to complete a gap analysis of basic health services utilization quality between urban and suburban areas. During the 6-year study period, there was an increasing trend toward greater efficiency of basic medical service provision, benefits of basic medical service provision, effectiveness of common chronic disease management, overall satisfaction of community residents, and two-way referral effects. In addition to the implementation effect of hypertension management and two-way referral, the remaining indicators showed a superior effect in urban areas compared with the suburbs (P<0.001). In addition, among the seven principal components, four principal component scores were better in urban areas than in suburban areas (P = <0.001, 0.004, 0.036, and 0.022). The urban comprehensive score also exceeded that of the suburbs (P<0.001). In summary, over the 6-year period, there was a rapidly increasing trend in basic medical service utilization. Comprehensive satisfaction clearly improved as well. Nevertheless, there was an imbalance in health service utilization between urban and suburban areas. There is a need for the health administrative department to address this imbalance between urban and suburban institutions and to provide the required support to underdeveloped areas to improve resident satisfaction. PMID- 29791471 TI - Brown bear (Ursus arctos) attacks resulting in human casualties in Scandinavia 1977-2016; management implications and recommendations. AB - Human persecution and habitat loss have endangered large carnivore populations worldwide, but some are recovering, exacerbating old conflicts. Carnivores can injure and kill people; the most dramatic form of wildlife-human conflict. In Scandinavia, the brown bear (Ursus arctos) population increased from ~500 bears in 1977 to ~3300 in 2008, with an increase in injuries, fatalities, and public fear of bear attacks. We reviewed media coverage and interviewed victims to explore how bear population trends, hunter education, and other factors may have influenced the number of injuries and fatalities in Scandinavia from 1977 to 2016. We found 42 incidents with 42 injuries and 2 fatalities; 42 were adult men, one was an adult woman conducting forestry work, and one was a boy skiing off piste. Thirty-three adult men were hunting bears, moose, or small game, often with a hunting dog, and 26 had shot at the bear at 8+/-11 m before injury. Eleven nonhunters were conducting forestry work, inspecting a hunting area, picking berries, tending livestock, hiking, harassing a denned bear, and one person was killed outside his house at night. Eight of the 11 incidents of nonhunters involved female bears with cubs; three of these family groups were in dens and two were on carcasses. The annual number of hunters injured/killed was mostly influenced by the increase in the bear population size. The pattern was similar regarding injuries/fatalities to other outdoor users, but the relation with the bear population size was weaker than for hunters, and the null model was equally supported. Bear physiology at denning may make encounters with bears more risky in the fall, when bears show prehibernation behavior. Awareness and education efforts, especially among hunters, seem important to ensure human safety. Recreationists and forestry workers should avoid dense vegetation or make noise to warn bears of their presence. PMID- 29791474 TI - Growth differentiation factor-15 levels and the risk of contrast induced nephropathy in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A retrospective observation study. AB - AIMS: To investigate the association between growth differentiation factor-15 (GDF-15) and contrast-induced nephropathy (CIN) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 311 patients with AMI were studied retrospectively. All patients were divided into two groups according to the occurrence of CIN after PCI. Baseline clinical data were compared between two groups. Multivariate logistic regression analysis was used to identify the risk factors for CIN. Cox regression analysis was used to identify the association between GDF-15, CIN and short-term outcome. RESULTS: There were 80 patients in CIN group (average age was 71.60 +/- 13.00 years; 67.5% male) and 231 patients in non-CIN group (average age was 63.80 +/- 11.70 years; 71.9%male). The concentration of GDF-15 in CIN group was higher than that of non-CIN group (1232 +/- 366.6 ng/L vs. 939.20 +/- 309.6 ng/L, P <0.001). According to GDF-15 quartiles, patients were divided into four groups. Multivariate logistic model indicated that the highest quartile(Q4) was significantly associated with an increased risk of CIN compared with lower level of GDF-15 (Q1, Q2 and Q3) (OR : 3.572, 1.803-7.078, P < 0.001). Of 243 patients who could calculate the ACEF risk score, area under the curve (AUC) of GDF-15 was 0.793, 95%CI: 0.729-0.856, P < 0.001, while AUC of ACEF was 0.708, 95%CI: 0.630 0.786, P < 0.001. Using 10% and 30% as arbitrary thresholds to define patients at low, intermediate, and high risk, GDF-15 achieved a net reclassification improvement (NRI) of 0.32 (95%CI: 0.123-0.518, P = 0.001) compared with the ACEF risk score. Cox regression model showed that high concentration of GDF-15 (Q4) was significantly associated with an increased risk of all-cause mortality and major adverse clinical events (MACE) (HR: 8.434, 95%CI: 2.650-26.837, P <0.001; HR: 3.562, 95%CI: 1.658-7.652, P = 0.001) compared with low level of GDF-15 (Q1, Q2 and Q3). CIN was an independent predictor of all-cause mortality and MACE in AMI patients (HR: 3.535, 95%CI: 1.135-11.005, P = 0.029; HR: 5.154, 95%CI: 2.228 11.925, P <0.001). CONCLUSION: GDF-15 levels increased in CIN group in AMI patients underwent PCI. GDF-15 was an independent risk factor for CIN in AMI patients underwent PCI. GDF-15 level and CIN are independent risk factors for all cause mortality and MACE in short-term follow-ups. PMID- 29791472 TI - Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway. AB - Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by gram-negative bacteria, induces autistic-like behaviors. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism. We selected pioglitazone to block or ease the impairments induced by LPS because although this drug was designed as an anti-diabetic drug (it has an insulin effect), it also exerts anti-inflammatory effects. Juvenile offspring were treated daily with pioglitazone, and the main behaviors related to autism, namely, socialization (play behavior) and communication (50-kHz ultrasonic vocalizations), were studied. Biomarkers linked to autism and/or pioglitazone were also studied to attempt to understand the mechanisms involved, namely, IL-6, TNF-alpha, MCP-1, insulin, and leptin. Prenatal LPS exposure induced social deficits and communicational abnormalities in juvenile rat offspring as well as elevated plasma IL-6 levels. Daily postnatal pioglitazone treatment blocked the impairments found in terms of the time spent on social interaction, the number of vocalizations (i.e., autistic-like behaviors) and the elevated plasma IL-6 levels. Thus, pioglitazone appears to be a relevant candidate for the treatment of autism. The present findings may contribute to a better understanding and treatment of autism and associated diseases. PMID- 29791475 TI - Ten-year experience with ophthalmic artery chemosurgery: Ocular and recurrence free survival. AB - PURPOSE: To report associations between disease- and treatment-related variables and rates of recurrence-free survival and ocular survival in eyes treated with ophthalmic artery chemosurgery (OAC) for retinoblastoma. DESIGN: Pre-post study. SUBJECTS: All eyes treated with OAC for retinoblastoma at Memorial Sloan Kettering Cancer Center between May 2006 and February 2017. METHODS: This retrospective review included 452 retinoblastoma eyes treated with OAC. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS), progression-free survival (PFS) and ocular survival (OcS), and Cox regression was used to estimate hazard ratios. Eyes treated in the pre-intravitreous chemotherapy era were analyzed separately from eyes treated in the intravitreal era. MAIN OUTCOME MEASURES: Recurrence-free survival, ocular survival, associations with risk of recurrence. RESULTS: Disease and treatment characteristics were recorded over a median 23.6 month follow-up. One-year OcS, PFS and RFS were 96% (95% CI 93-99%), 88% (95% CI 88-94%) and 74% (95% CI 67-81%) in the pre-intravitreal era and 96% (95% CI 94-99%), 93% (95% CI 89-96%) and 78% (95% CI 72-83%) in the intravitreal era, respectively. Presence of vitreous seeds was associated with increased risk of recurrence in the pre-intravitreal era but not in the intravitreal era. Longer time interval between OAC sessions was associated with increased risk of recurrence and majority OAC access via the ophthalmic artery was associated with decreased risk of recurrence in both eras. CONCLUSIONS: Approximately a quarter of eyes initially treated with ophthalmic artery chemosurgery develop recurrent disease, with the majority of recurrences within the first year following completion of OAC. Despite this, these eyes have a very good chance of salvage. In eyes with vitreous seeds at presentation, intravitreal injections are useful in minimizing future vitreous recurrence. Eyes that receive the majority of drug infusions via non-ophthalmic artery routes or greater interval between OAC are more likely to recur and might warrant closer monitoring. PMID- 29791473 TI - The fecal bacterial microbiota of bats; Slovenia. AB - METHODS: Fecal samples were collected from 92 bats in Slovenia, consisting of 12 different species, and the bacterial microbiota was assessed via next generation sequencing of the 16S rRNA gene V4 region. RESULTS: Sequences were assigned to 28 different phyla, but only Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria accounted for >=1% of sequences. One phylum (Proteobacteria), one class (Gammaproteobacteria), three orders (Pseudomonadales, Lactobacillales, Bacillales), four families (Enterobacteriaceae, Pseudomonadaceae, Staphylococcaceae, Carnobacteriaceae), and five genera (Pseudomonas, Staphylococcus, Carnobacterium, an unclassified Enterobacteriaceae, Acinetobacter) accounted for 50% of sequences. There were no significant differences in the relative abundances of any phyla between bat species, but various differences were noted at lower taxonomic levels, such as Enterobacteriaceae (P = 0.007, most abundant in M. blythii), Pseudomonadaceae (P = 0.007, most abundant in Rhinolophus hipposideros) and Chlamydiaceae (P = 0.04, most abundant in Myotis myotis). There were significant differences in richness between species in both adults and juveniles/subadults, but there was no impact of sex on any alpha diversity index. When only adults are considered, there were significant differences in community membership between M. blythii and M. emarginatus (P = 0.011), and M. blythii and R. hipposideros (P = 0.004). There were also significant differences in community structure between M. blythii and M. emarginatus (P = 0.025), and M. blythii and R. hipposideros (P = 0.026). When adults of the four main species were compared, 14 OTUs were identified as differentially abundant using LEfSe. Only one difference was identified when comparing R. hipposideros adults and juvenile/subadults, with Klebsiella over represented in the younger bats. CONCLUSIONS: Bats have a complex and diverse microbiota with a high relative abundance of Proteobacteria. The relevance of this difference is unclear and requires further study. Differences in the microbiota were observed between bat species, perhaps reflecting different diets and environmental exposures. PMID- 29791476 TI - Identifying county characteristics associated with resident well-being: A population based study. AB - BACKGROUND: Well-being is a positively-framed, holistic assessment of health and quality of life that is associated with longevity and better health outcomes. We aimed to identify county attributes that are independently associated with a comprehensive, multi-dimensional assessment of individual well-being. METHODS: We performed a cross-sectional study examining associations between 77 pre-specified county attributes and a multi-dimensional assessment of individual US residents' well-being, captured by the Gallup-Sharecare Well-Being Index. Our cohort included 338,846 survey participants, randomly sampled from 3,118 US counties or county equivalents. FINDINGS: We identified twelve county-level factors that were independently associated with individual well-being scores. Together, these twelve factors explained 91% of the variance in individual well-being scores, and they represent four conceptually distinct categories: demographic (% black); social and economic (child poverty, education level [ 0.24 mg/dl (median SCr absolute increase), delta NGAL 0-6 hours and 6-hours NGAL values were higher compared with patients with SCr elevation below the defined threshold (p = 0.049 and p = 0.056). The ROC analysis showed that a 6 hours NGAL value > 96 ng/ml significantly predicted an absolute SCr increase > 0.24 mg/dl after contrast exposure with sensitivity of 53% and specificity of 74% (AUC 0.819, 95% CI: 0.656 to 0.983, p = 0.005). The use of bedside NGAL assessment may significantly hasten diagnosis and treatment of CI-AKI, with remarkable clinical prognostic consequences. PMID- 29791498 TI - A systematic approach to parameter selection for CAD-virtual reality data translation using response surface methodology and MOGA-II. AB - Advanced graphics capabilities have enabled the use of virtual reality as an efficient design technique. The integration of virtual reality in the design phase still faces impediment because of issues linked to the integration of CAD and virtual reality software. A set of empirical tests using the selected conversion parameters was found to yield properly represented virtual reality models. The reduced model yields an R-sq (pred) value of 72.71% and an R-sq (adjusted) value of 86.64%, indicating that 86.64% of the response variability can be explained by the model. The R-sq (pred) is 67.45%, which is not very high, indicating that the model should be further reduced by eliminating insignificant terms. The reduced model yields an R-sq (pred) value of 73.32% and an R-sq (adjusted) value of 79.49%, indicating that 79.49% of the response variability can be explained by the model. Using the optimization software MODE Frontier (Optimization, MOGA-II, 2014), four types of response surfaces for the three considered response variables were tested for the data of DOE. The parameter values obtained using the proposed experimental design methodology result in better graphics quality, and other necessary design attributes. PMID- 29791496 TI - PBP2b plays a key role in both peripheral growth and septum positioning in Lactococcus lactis. AB - Lactococcus lactis is an ovoid bacterium that forms filaments during planktonic and biofilm lifestyles by uncoupling cell division from cell elongation. In this work, we investigate the role of the leading peptidoglycan synthase PBP2b that is dedicated to cell elongation in ovococci. We show that the localization of a fluorescent derivative of PBP2b remains associated to the septal region and superimposed with structural changes of FtsZ during both vegetative growth and filamentation indicating that PBP2b remains intimately associated to the division machinery during the whole cell cycle. In addition, we show that PBP2b-negative cells of L. lactis are not only defective in peripheral growth; they are also affected in septum positioning. This septation defect does not simply result from the absence of the protein in the cell growth machinery since it is also observed when PBP2b-deficient cells are complemented by a catalytically inactive variant of PBP2b. Finally, we show that round cells resulting from beta-lactam treatment are not altered in septation, suggesting that shape elongation as such is not a major determinant for selection of the division site. Altogether, we propose that the specific PBP2b transpeptidase activity at the septum plays an important role for tagging future division sites during L. lactis cell cycle. PMID- 29791497 TI - Xenin is a novel anorexigen in goldfish (Carassius auratus). AB - Xenin, a highly conserved 25 amino acid peptide cleaved from the N-terminus of the coatomer protein alpha (COPA), is emerging as a food intake regulator in mammals and birds. To date, no research has been conducted on xenin biology in fish. This study aims to identify the copa mRNA encoding xenin in goldfish (Carassius auratus) as a model, to elucidate its regulation by feeding, and to describe the role of xenin on appetite. First, a partial sequence of copa cDNA, a region encoding xenin, was identified from goldfish brain. This sequence is highly conserved among both vertebrates and invertebrates. RT-qPCR revealed that copa mRNAs are widely distributed in goldfish tissues, with the highest levels detected in the brain, gill, pituitary and J-loop. Immunohistochemistry confirmed also the presence of COPA peptide in the hypothalamus and enteroendocrine cells on the J-loop mucosa. In line with its anorexigenic effects, we found important periprandial fluctuations in copa mRNA expression in the hypothalamus, which were mainly characterized by a gradually decrease in copa mRNA levels as the feeding time was approached, and a gradual increase after feeding. Additionally, fasting differently modulated the expression of copa mRNA in a tissue-dependent manner. Peripheral and central injections of xenin reduce food intake in goldfish. This research provides the first report of xenin in fish, and shows that this peptide is a novel anorexigen in goldfish. PMID- 29791500 TI - Retraction: Calcium Channel Blockers and Risk of Breast Cancer: A Meta-Analysis of 17 Observational Studies. PMID- 29791499 TI - Perturbation of the metabolic network in Salmonella enterica reveals cross-talk between coenzyme A and thiamine pathways. AB - Microorganisms respond to a variety of metabolic perturbations by repurposing or recruiting pathways to reroute metabolic flux and overcome the perturbation. Elimination of the 2-dehydropantoate 2-reductase, PanE, both reduces total coenzyme A (CoA) levels and causes a conditional HMP-P auxotrophy in Salmonella enterica. CoA or acetyl-CoA has no demonstrable effect on the HMP-P synthase, ThiC, in vitro. Suppressors aimed at probing the connection between the biosynthesis of thiamine and CoA contained mutations in the gene encoding the ilvC transcriptional regulator, ilvY. These mutations may help inform the structure and mechanism of action for the effector-binding domain, as they represent the first sequenced substitutions in the effector-binding domain of IlvY that cause constitutive expression of ilvC. Since IlvC moonlights as a 2 dehydropantoate 2-reductase, the resultant increase in ilvC transcription increased synthesis of CoA. This study failed to identify mutations overcoming the need for CoA for thiamine synthesis in S. enterica panE mutants, suggesting that a more integrated approach may be necessary to uncover the mechanism connecting CoA and ThiC activity in vivo. PMID- 29791501 TI - Stillbirths in urban Guinea-Bissau: A hospital- and community-based study. AB - BACKGROUND: Stillbirth rates remain high in many low-income settings, with fresh (intrapartum) stillbirths accounting for a large part due to limited obstetrical care. We aimed to determine the stillbirth rate and identify potentially modifiable factors associated with stillbirth in urban Guinea-Bissau. METHODS: The study was carried out by the Bandim Health Project (BHP), a Health and Demographic Surveillance System site in the capital Bissau. We assessed stillbirth rates in a hospital cohort consisting of all deliveries at the maternity ward at the National Hospital Simao Mendes (HNSM), and in a community cohort, which only included women from the BHP area. Stillbirth was classified as fresh (FSB) if fetal movements were reported on the day of delivery. RESULTS: From October 1 2007 to April 15 2013, a total of 38164 deliveries were registered at HNSM, among them 3762 stillbirths (99/1000 births). Excluding deliveries referred to the hospital from outside the capital (9.6%), the HNSM stillbirth rate was 2786/34490 births (81/1000). During the same period, 15462 deliveries were recorded in the community cohort. Of these, 768 were stillbirths (50/1000). Of 11769 hospital deliveries among women from Bissau with data on fetal movement, 866 (74/1000) were stillbirths, and 609 (70.3%) of these were FSB, i.e. potentially preventable. The hospital FSB rate was highest in the evening from 4 pm to midnight (P = 0.04). In the community cohort, antenatal care (ANC) attendance correlated strongly with stillbirth reduction; the stillbirth rate was 71/1000 if the mother attended no ANC consultations vs. 36/1000 if she attended >=7 consultations (P<0.001). CONCLUSION: In Bissau, the stillbirth rate is alarmingly high. The majority of stillbirths are preventable FSB. Improving obstetrical training, labour management (including sufficient intrapartum monitoring and timely intervention) and hospital infrastructure is urgently required. This should be combined with proper community strategies and additional focus on antenatal care. PMID- 29791502 TI - Anthropometry-based 24-h urinary creatinine excretion reference for Chinese children. AB - To establish 24-h urinary creatinine excretion reference ranges based on anthropometry in healthy Chinese children, a cross-sectional survey was conducted using twice-sampled 24-h urine and anthropometric variables. Age- and sex specific 24-h creatinine excretion reference ranges (crude and related to individual anthropometric variables) were derived. During October 2013 and May 2014, urine samples were collected. Anthropometric variables were measured in the first survey. Data of 710 children (377 boys and 333 girls) aged 8-13 years who completed the study were analyzed. No significant difference was observed in 24-h urine volumes between the two samples (median [interquartile range): 855.0 [600.0 1272.0) mL vs. 900.0 [660.0-1220.0) mL, P = 0.277). The mean 24-h urine creatinine excretion was regarded as representative of absolute daily creatinine excretion in children. Sex-specific, body-weight-adjusted creatinine excretion reference values were 15.3 mg/kg/day (0.1353 mmol/kg/day) for boys and 14.3 mg/kg/day (0.1264 mmol/kg/day) for girls. Differences were significant between boys and girls within the same age group but not across different age groups within the same sex. Ideal 24-h creatinine excretion values for height were derived for potential determination of the creatinine height index. These data can serve as reference ranges to calculate ratios of analyte to creatinine. The creatinine height index can be used to assess somatic protein status. PMID- 29791504 TI - Periconceptional maternal dairy-rich dietary pattern is associated with prenatal cerebellar growth. AB - BACKGROUND: Maternal nutrition during pregnancy has been related to intrauterine brain development and neurodevelopmental disabilities in adult life. We aim to investigate associations between periconceptional maternal dietary patterns and prenatal cerebellar growth from the first trimester onwards. MATERIALS AND METHODS: 126 women with singleton non-malformed pregnancies were enrolled before 8 weeks of gestation in the Rotterdam periconceptional cohort between 2013 and 2015. Periconceptional maternal dietary patterns were extracted from food frequency questionnaires and associated with blood biomarkers and micronutrient intakes. Serial two-dimensional and three-dimensional ultrasound scans were performed at 9, 11, 22, 26 and 32 weeks of gestation for transcerebellar diameter (TCD) measurement. Linear mixed models were estimated to investigate associations between periconceptional maternal dietary patterns and longitudinal TCD measurements as a function of gestational age. RESULTS: We performed a median of 4 scans per pregnancy, resulting in 570 total datasets. The success rate of TCD measurements was 87% (range 65-100%), depending on gestational age. The Mediterranean, Western, egg-rich and dairy-rich dietary patterns were extracted, explaining 37.2% of the overall variance of food intake in this population. The dairy-rich dietary pattern was positively associated with cerebellar growth trajectories (beta = 0.02 (95% CI: 0.01; 0.03) ?mm, p = 0.01). Maternal strong adherence to this dietary pattern increased TCD measurements by 0.8 standard deviation scores (SDs) compared to weak adherence, reflected in increased TCD estimates of 0.44 mm at 9 weeks (+6.8%), 0.88 mm at 22 weeks (+3.6%), and 1.17 mm at 32 weeks (+2.8%). No significant associations were detected for the Mediterranean, Western and egg-rich dietary patterns. CONCLUSIONS: This study shows a positive association between periconceptional maternal adherence to a dairy-rich dietary pattern and human prenatal TCD measurements as a proxy of cerebellar growth. Next step is the investigation of the impact on neurodevelopmental outcomes in the offspring. PMID- 29791503 TI - [18F]FDG and [18F]FLT PET for the evaluation of response to neo-adjuvant chemotherapy in a model of triple negative breast cancer. AB - RATIONALE: Pathological response to neo-adjuvant chemotherapy (NAC) represents a commonly used predictor of survival in triple negative breast cancer (TNBC) and the need to identify markers that predict response to NAC is constantly increasing. Aim of this study was to evaluate the potential usefulness of PET imaging with [18F]FDG and [18F]FLT for the discrimination of TNBC responders to Paclitaxel (PTX) therapy compared to the response assessed by an adapted Response Evaluation Criteria In Solid Tumors (RECIST) criteria based on tumor volume (Tumor Volume Response). METHODS: Nu/nu mice bearing TNBC lesions of different size were evaluated with [18F]FDG and [18F]FLT PET before and after PTX treatment. SUVmax, Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) and Proliferation (TLP) were assessed using a graph-based random walk algorithm. RESULTS: We found that in our TNBC model the variation of [18F]FDG and [18F]FLT SUVmax similarly defined tumor response to therapy and that SUVmax variation represented the most accurate parameter. Response evaluation using Tumor Volume Response (TVR) showed that the effectiveness of NAC with PTX was completely independent from lesions size at baseline. CONCLUSIONS: Our study provided interesting results in terms of sensitivity and specificity of PET in TNBC, revealing the similar performances of [18F]FDG and [18F]FLT in the identification of responders to Paclitaxel. PMID- 29791505 TI - Rapid direct aperture optimization via dose influence matrix based piecewise aperture dose model. AB - In the traditional two-step procedure used in intensity-modulated radiation therapy, fluence map optimization (FMO) is performed first, followed by use of a leaf sequencing algorithm (LSA). By contrast, direct aperture optimization (DAO) directly optimizes aperture leaf positions and weights. However, dose calculation using the Monte Carlo (MC) method for DAO is often time-consuming. Therefore, a rapid DAO (RDAO) algorithm is proposed that uses a dose influence matrix based piecewise aperture dose model (DIM-PADM). In the proposed RDAO algorithm, dose calculation is based on the dose influence matrix instead of MC. The dose dependence of aperture leafs is modeled as a piecewise function using the DIM. The corresponding DIM-PADM-based DAO problem is solved using a simulated annealing algorithm.The proposed algorithm was validated through application to TG119, prostate, liver, and head and neck (H&N) cases from the common optimization for radiation therapy dataset. Compared with the two-step FMO-LSA procedure, the proposed algorithm resulted in more precise dose conformality in all four cases. Specifically, for the H&N dataset, the cost value for the planned target volume (PTV) was decreased by 32%, whereas the cost value for the two organs at risk (OARs) was decreased by 60% and 92%. Our study of the proposed novel DIM-PADM-based RDAO algorithm makes two main contributions: First, we validate the use of the proposed algorithm, in contrast to the FMO-LSA framework, for direct optimization of aperture leaf positions and show that this method results in more precise dose conformality. Second, we demonstrate that compared to MC, the DIM-PADM-based method significantly reduces the computational time required for DAO. PMID- 29791506 TI - SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy. AB - HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the molecular target of JIB-04, a small molecule compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass spectrometry analysis of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex. Importantly, knockdown of SHMT1,2 or BRCC36, or exposure of cells to JIB-04, strongly increased Tat K63Ub-dependent destruction via autophagy. Moreover, point mutation of multiple lysines in Tat, or knockdown of BRCC36 or SHMT1,2, was sufficient to prevent destruction of Tat by JIB-04. We conclude that HIV-1 Tat levels are regulated through K63Ub-selective autophagy mediated through SHMT1,2 and the BRCC36 deubiquitinase. PMID- 29791508 TI - Does arterial hypertension influence the onset of Huntington's disease? AB - Huntington's disease (HD) age of onset (AO) is mainly determined by the length of the CAG repeat expansion in the huntingtin gene. The remaining AO variability has been attributed to other little-known factors. A factor that has been associated with other neurodegenerative diseases is arterial hypertension (AHT). The aim of this study is to evaluate the contribution of AHT to the AO of HD. We used data from a cohort of 630 European HD patients with adult onset collected by the REGISTRY project of the European Huntington's Disease Network. Multiple linear regression and ANOVA, controlling for the CAG repeat number of the expanded allele (CAGexp) of each patient, were performed to assess the association between the AHT condition and the AO of the motor symptoms (mAO). The results showed a significant association between AHT and mAO, especially when we only considered the patients diagnosed with AHT prior to manifesting any HD signs (pre-HD AHT). Remarkably, despite the low number of cases, those patients developed motor symptoms 5-8 years later than normotensive patients in the most frequent CAGexp range (40-44). AHT is an age-related condition and consequently, the age of the patient at the time of data collection could be a confounder variable. However, given that most pre-HD AHT patients included in our study had started treatment with antihypertensive drugs prior to the onset of HD, and that antihypertensive drugs have been suggested to confer a neuroprotective effect in other neurodegenerative diseases, raises the interest in elucidating the impact of AHT and/or AHT treatment in HD age of onset in further studies. A confirmation of our results in a larger sample set would open the possibility to significantly improve HD management. PMID- 29791507 TI - A novel mouse model of Campylobacter jejuni enteropathy and diarrhea. AB - Campylobacter infections are among the leading bacterial causes of diarrhea and of 'environmental enteropathy' (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress. PMID- 29791509 TI - Health outcomes and adherence to a healthy lifestyle after a multimodal intervention in people with multiple sclerosis: Three year follow-up. AB - BACKGROUND: Modifiable risk factors such as smoking and sedentary lifestyle adversely affect multiple sclerosis (MS) progression. Few multimodal behavioural interventions have been conducted for people with MS, and follow-up beyond 1 year is rare for lifestyle interventions. This study assessed adoption and adherence to healthy lifestyle behaviours and health outcomes 3 years after a lifestyle modification intervention, using generalized estimating equation models to account for within-participant correlation over time. METHODS: 95 people with MS completed baseline surveys before participating in 5-day MS lifestyle risk-factor modification workshops. 76 and 78 participants completed the 1-year and 3-year follow-up surveys respectively. Mean age at 3-year follow-up was 47 years, 72% were female, most (62.8%) had MS for 5 years or less, and 73% had relapsing remitting MS (RRMS). RESULTS: Compared to baseline, participants reported clinically meaningful increases in physical (mean difference (MD): 8.0, 95% Confidence Interval (CI): 5.2-10.8) and mental health (MD: 9.2, CI: 5.8-12.6) quality of life (QOL) at 1-year, and physical (MD: 8.7, CI: 5.3-12.2) and mental health (MD: 8.0, CI: 4.2-11.8) QOL at 3-year follow-up. There was a small decrease in disability from baseline to 1-year follow-up (MD: 0.9, CI: 0.9,1.0) and to 3-year follow-up (MD: 1.0, CI: 0.9,1.0), which was not clinically meaningful. Of those with RRMS, compared to baseline, fewer had a relapse during the year before 1-year follow-up (OR: 0.1, CI 0.0-0.2) and 3-year follow-up (OR: 0.15, CI 0.06-0.33). Participants' healthy diet score, the proportion meditating >=1 hours a week, supplementing with >= 5000IU vitamin D daily, and supplementing with omega-3 flaxseed oil increased at 1-year follow-up and was sustained, although slightly lower at 3-year follow-up. However, there was no evidence for a change in physical activity and not enough smokers to make meaningful comparisons. Medication use increased at 1-year follow-up and at 3-year follow up. CONCLUSION: The results provide evidence that lifestyle risk factor modification is feasible and sustainable over time, in a small self-selected and motivated sample of people with MS. Furthermore, participation in a lifestyle intervention is not associated with a decrease in MS medication use. PMID- 29791510 TI - The importance of manager support for the mental health and well-being of ambulance personnel. AB - Interventions to enhance mental health and well-being within high risk industries such as the emergency services have typically focused on individual-level factors, though there is increasing interest in the role of organisational-level interventions. The aim of this study was to examine the importance of different aspects of manager support in determining the mental health of ambulance personnel. A cross-sectional survey was completed by ambulance personnel across two Australian states (N = 1,622). Demographics, manager support and mental health measures were assessed. Hierarchical multiple linear regressions were conducted to determine the explanatory influence of the employee's perception of the priority management places upon mental health issues (manager psychosocial safety climate) and managers' observed behaviours (manager behaviour) on employee common mental disorder and well-being within ambulance personnel. Of the 1,622 participants, 123 (7.6%) were found to be suffering from a likely mental disorder. Manager psychosocial safety climate accounted for a significant amount of the variance in levels of employee common mental health disorder symptoms (13%, p<0.01) and well-being (13%, p<0.01). Manager behaviour had a lesser, but still statistically significant influence upon symptoms of common mental disorder (7% of variance, p<0.01) and well-being (10% of variance, p<0.05). The perceived importance management places on mental health and managers' actual behaviour are related but distinct concepts, and each appears to impact employee mental health. While the overall variance explained by each factor was limited, the fact that each is potentially modifiable makes this finding important and highlights the significance of organisational and team-level interventions to promote employee well-being within emergency services and other high-risk occupations. PMID- 29791511 TI - Caspase-11-dependent pyroptosis of lung epithelial cells protects from melioidosis while caspase-1 mediates macrophage pyroptosis and production of IL 18. AB - Infection with Burkholderia pseudomallei or B. thailandensis triggers activation of the NLRP3 and NLRC4 inflammasomes leading to release of IL-1beta and IL-18 and death of infected macrophages by pyroptosis, respectively. The non-canonical inflammasome composed of caspase-11 is also activated by these bacteria and provides protection through induction of pyroptosis. The recent generation of bona fide caspase-1-deficient mice allowed us to reexamine in a mouse model of pneumonic melioidosis the role of caspase-1 independently of caspase-11 (that was also absent in previously generated Casp1-/- mice). Mice lacking either caspase-1 or caspase-11 were significantly more susceptible than wild type mice to intranasal infection with B. thailandensis. Absence of caspase-1 completely abolished production of IL-1beta and IL-18 as well as pyroptosis of infected macrophages. In contrast, in mice lacking caspase-11 IL-1beta and IL-18 were produced at normal level and macrophages pyroptosis was only marginally affected. Adoptive transfer of bone marrow indicated that caspase-11 exerted its protective action both in myeloid cells and in radio-resistant cell types. B. thailandensis was shown to readily infect mouse lung epithelial cells triggering pyroptosis in a caspase-11-dependent way in vitro and in vivo. Importantly, we show that lung epithelial cells do not express inflammasomes components or caspase-1 suggesting that this cell type relies exclusively on caspase-11 for undergoing cell death in response to bacterial infection. Finally, we show that IL-18's protective action in melioidosis was completely dependent on its ability to induce IFNgamma production. In turn, protection conferred by IFNgamma against melioidosis was dependent on generation of ROS through the NADPH oxidase but independent of induction of caspase-11. Altogether, our results identify two non-redundant protective roles for caspase-1 and caspase-11 in melioidosis: Caspase-1 primarily controls pyroptosis of infected macrophages and production of IL-18. In contrast, caspase-11 mediates pyroptosis of infected lung epithelial cells. PMID- 29791512 TI - CPR-IR is an insulin resistance index that is minimally affected by hepatic insulin clearance-A preliminary research. AB - BACKGROUND: Increased hepatic insulin clearance (HIC) is important in the pathophysiology of type 2 diabetes mellitus (T2DM). The aim of this study is to analyze an effective insulin resistance (IR) index that is minimally affected by HIC. METHODS: Our study involved 20 participants with T2DM and 21 healthy participants without diabetes (Non-DM). Participants underwent a meal tolerance test from which plasma glucose, insulin and serum C-peptide immunoreactivity (CPR) were measured, and HOMA-IR and HIC were calculated. Participants then underwent a hyperinsulinemic-euglycemic clamp from which the glucose disposal rate (GDR) was measured. RESULTS: The index CPR-IR = 20/(fasting CPR * fasting plasma glucose) was correlated more strongly with GDR, than was HOMA-IR, and CPR IR could be used to estimate GDR. In T2DM participants with HIC below the median, HOMA-IR and CPR-IR were equally well correlated with GDR. In T2DM with high HIC, CPR-IR correlated with GDR while HOMA-IR did not. In Non-DM, CPR-IR and HOMA-IR were equally well correlated with GDR regardless of HIC. The mean HIC value in T2DM was significantly higher than that of Non-DM. CONCLUSIONS: CPR-IR could be a simple and effective index of insulin resistance for patients with type 2 diabetes that is minimally affected by HIC. PMID- 29791515 TI - Comparison of oscillometric, Doppler and invasive blood pressure measurement in anesthetized goats. AB - Arterial blood pressure (BP) can be measured directly using an invasive intra arterial method. This method is considered a gold standard, however it is potentially hazardous and requires expensive equipment and professional skills. Therefore, two non-invasive methods-Doppler ultrasonic sphygmomanometry and oscillometry-have been introduced in veterinary medicine. Their accuracy has so far been reliably evaluated in various animal species, however only one study included a small group of goats. Therefore, we carried out a large-scale study which aimed to evaluate agreement between the two non-invasive methods and invasive intra-arterial BP measurement in anesthetized goats at various age. The study included 122 goats of two Polish local breeds (Polish White Improved and Polish Fawn Improved): 67 adult females, 35 adult males, and 20 two-month-old female kids. Goats were anesthetized with the intravenous mixture of xylazine and ketamine. BP was measured simultaneously with the three methods in each goat with 7 measurements on average taken. The study showed that according to the criteria of the American College of Veterinary Internal Medicine (ACVIM) oscillometric method yielded BP measurements sufficiently consistent with invasive intra arterial method in anesthetized adult goats- 95% of oscillometric BP measurements were expected to differ from invasive BP measurements by at most +/-20-25 mmHg. The agreement was worse in goat kids-oscillometry significantly overestimated invasive BP measurements, which resulted in highly asymmetrical 95% limits of agreement. Doppler systolic BP very poorly conformed to invasive systolic BP both in adult goats and in kids and all the ACVIM criteria were violated. Concluding, oscillometry, but not Doppler ultrasonic sphygmomanometry, may be regarded as an alternative to invasive BP measurement in large-scale scientific studies involving adult goats, however, individual oscillometric BP measurements should be treated with caution as estimated 95% limits of agreement were wide. PMID- 29791513 TI - Vaccine-induced antibodies to herpes simplex virus glycoprotein D epitopes involved in virus entry and cell-to-cell spread correlate with protection against genital disease in guinea pigs. AB - Herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit antigen is included in many preclinical candidate vaccines. The rationale for including gD2 is to produce antibodies that block crucial gD2 epitopes involved in virus entry and cell-to-cell spread. HSV-2 gD2 was the only antigen in the Herpevac Trial for Women that protected against HSV-1 genital infection but not HSV-2. In that trial, a correlation was detected between gD2 ELISA titers and protection against HSV-1, supporting the importance of antibodies. A possible explanation for the lack of protection against HSV-2 was that HSV-2 neutralization titers were low, four-fold lower than to HSV-1. Here, we evaluated neutralization titers and epitope-specific antibody responses to crucial gD2 epitopes involved in virus entry and cell-to-cell spread as correlates of immune protection against genital lesions in immunized guinea pigs. We detected a strong correlation between neutralizing antibodies and protection against genital disease. We used a high throughput biosensor competition assay to measure epitope-specific responses to seven crucial gD2 linear and conformational epitopes involved in virus entry and spread. Some animals produced antibodies to most crucial epitopes while others produced antibodies to few. The number of epitopes recognized by guinea pig immune serum correlated with protection against genital lesions. We confirmed the importance of antibodies to each crucial epitope using monoclonal antibody passive transfer that improved survival and reduced genital disease in mice after HSV-2 genital challenge. We re-evaluated our prior study of epitope-specific antibody responses in women in the Herpevac Trial. Humans produced antibodies that blocked significantly fewer crucial gD2 epitopes than guinea pigs, and antibody responses in humans to some linear epitopes were virtually absent. Neutralizing antibody titers and epitope-specific antibody responses are important immune parameters to evaluate in future Phase I/II prophylactic human vaccine trials that contain gD2 antigen. PMID- 29791514 TI - High prevalence of syndemic health problems in patients seeking post-exposure prophylaxis for sexual exposures to HIV. AB - INTRODUCTION: The standard clinical approach to non-occupational HIV post exposure prophylaxis (nPEP) focuses on biomedical aspects of the intervention, but may overlook co-occurring or 'syndemic' psychosocial problems that reinforce future vulnerability to HIV. We therefore sought to determine the prevalence of syndemic health problems in a cohort of Ontario nPEP patients, and explored the relationship between syndemic burden and HIV risk. METHODS: Between 07/2013 08/2016, we distributed a self-administered questionnaire to patients presenting to three clinics in Toronto and Ottawa seeking nPEP for sexual HIV exposures. We used validated screening tools to estimate the prevalence of depression (CES-D score >=16), harmful alcohol use (AUDIT >=8), problematic drug use (DUDIT >=6 men/>=2 women), and sexual compulsivity (SCS >=24) among men who have sex with men (MSM) respondents. In exploratory analyses, we examined the relationships between syndemic conditions using univariable logistic regression models, and the relationship between syndemic count (total number of syndemic conditions per participant) and HIV risk, as estimated by the HIRI-MSM score, using linear regression models. RESULTS: The 186 MSM included in the analysis had median age 31 (IQR = 26-36), including 87.6% having a college/undergraduate degree or higher. Overall, 53.8% screened positive for depression, 34.4% for harmful alcohol use, 30.1% for problematic drug use, and 16.1% for sexual compulsivity. Most participants (74.2%) had at least one syndemic condition and 46.8% had more than one. Exploratory analyses suggested positive associations between depression and harmful alcohol use (OR = 2.11, 95%CI = 1.13, 3.94) and between harmful alcohol use and problematic drug use (OR = 1.22, 95%CI = 0.65, 2.29). Syndemic count was associated with increased HIRI-MSM risk scores in univariable (2.2, 95%CI = 1.0, 3.3 per syndemic condition) and multivariable (2.1, 95%CI = 0.6, 3.6) linear regression models. CONCLUSIONS: The prevalence of syndemic conditions in MSM seeking nPEP for sexual exposure is alarmingly high, and is associated with underlying HIV risk. Routine screening for these conditions may identify opportunities for intervention and could alleviate future vulnerability to HIV. PMID- 29791517 TI - Costs of cold acclimation on survival and reproductive behavior in Drosophila melanogaster. AB - Fitness is determined by the ability of an organism to both survive and reproduce; however, the mechanisms that lead to increased survival may not have the same effect on reproductive success. We used nineteen natural Drosophila melanogaster genotypes from the Drosophila Genetic Reference Panel to determine if adaptive plasticity following short-term acclimation through rapid cold hardening (RCH) affects mating behavior and mating success. We confirmed that exposure to the acclimation temperature is beneficial to survival following cold stress; however, we found that this same acclimation temperature exposure led to less efficient male courtship and a significant decrease in the likelihood of mating. Cold tolerance and the capacity to respond plastically to cold stress were not correlated with mating behavior following acclimation, suggesting that the genetic control of the physiological effects of the cold temperature exposure likely differ between survival and behavioral responses. We also tested whether the exposure of males to the acclimation temperature influenced courtship song. This exposure again significantly increased courtship duration; however, courtship song was unchanged. These results illustrate costs of short-term acclimation on survival and reproductive components of fitness and demonstrate the pronounced effect that short-term thermal environment shifts can have on reproductive success. PMID- 29791516 TI - The relevance of restrained eating behavior for circadian eating patterns in adolescents. AB - BACKGROUND: Restrained Eating, i.e. the tendency to restrict dietary intake to control body-weight, often emerges during adolescence and may result in changes in circadian eating patterns. OBJECTIVE: The objective of the present investigation was to determine the cross-sectional relevance of restrained eating for characteristics of circadian eating pattern in adolescents and whether changes in restrained eating are accompanied by concurrent changes in circadian eating pattern over the course of adolescence. METHODS: Two questionnaires assessing restrained eating (Score 0-30) with parallel 3-day weighed dietary records from two different time points were available from 209 (?:101, ?:108) 11 18 year old adolescents of the DONALD study. Mixed linear regression models were used to analyze whether restrained eating was associated with eating occasion frequency, snack frequency and morning and evening energy intake [in % of daily energy intake, %E]. Linear regression models were used to examine whether changes in restrained eating were associated with changes in the mentioned variables. RESULTS: Among girls, greater restrained eating was cross-sectionally associated with higher morning energy intake (p = 0.03). Further, there was a tendency towards lower evening energy intake with higher levels of restrained eating for the whole sample (p = 0.06). No cross-sectional associations were found with eating occasion or snack frequency. Each one-point increase in restrained eating during adolescence was related to a concurrent decrease in eating occasion frequency by 0.04 (95% CI -0.08; -0.01, p = 0.02) and in evening energy intake by 0.36%E (95% CI -0.70; -0.03, p = 0.04). A tendency towards decreasing snack frequency with increasing restrained eating was observed (beta = -0.03, 95% CI 0.07; 0.00, p = 0.07). No association was found between changes in restrained eating and concurrent changes in morning energy intake. CONCLUSION: We found indications for cross-sectional and prospective associations between restrained eating and chronobiological aspects of food intake in adolescents. Our results suggest that restrained eating should be considered a relevant determinant of circadian eating patterns. PMID- 29791519 TI - Physical quality of seeds of Moquiniastrum polymorphum. AB - This study aimed to analyze the physical properties of the seeds of Moquiniastrum polymorphum when processed by mini-SAS, X-ray and seed blower systems. The seeds were purchased from Seeds Caicara, located in Penapolis-SP. After purchase, the seed lot was characterized by standard tests. In the X-ray test the seeds were classified according to their internal morphology as filled, unfilled or malformed. The seed blower was set at six opening settings, resulting in light and heavy fractions. The evaluations were performed by weighing the seeds that remained in the blower (heavy fraction) and by the amount of filled seeds indicated by the X-ray test. The germination tests were composed of four replicates of 50 seeds. The mini-SAS was used for external evaluation. It was concluded that the combined use of the seed blower and the X-ray test was efficient for the evaluation and determination of the physical quality of the seeds of M. polymorphum. The seed blower at opening settings 5 resulted in the best lot quality. The external parameters were not able to qualitatively evaluate the seeds of M. polymorphum. PMID- 29791520 TI - Use of direct oral anticoagulants for chronic thromboembolic pulmonary hypertension. AB - OBJECTIVES: Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study. RESULTS: Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall. CONCLUSIONS: Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use. PMID- 29791518 TI - Multi-Operational Selective Computer-Assisted Targeting of hepatocellular carcinoma-Evaluation of a novel approach for navigated tumor ablation. AB - OBJECTIVE: To facilitate precise local ablation of hepatocellular carcinoma (HCC) in a setting of combined ablation and transarterial chemoembolization (TACE), we evaluated accuracy and efficiency of a novel technique for navigated positioning of ablation probes using intrahepatic tumor referencing and electromagnetic (EM) guidance, in a porcine model. METHODS: An angiographic wire with integrated EM reference sensor at its tip was inserted via a transarterial femoral access and positioned in the vicinity of artificial liver tumors. The resulting offset distance between the tumor center and the intrahepatic endovascular EM reference was calculated. Subsequently, EM tracked ablation probes were inserted percutaneously and navigated toward the tumor center, relying on continuous EM guidance via the intrahepatic reference. Targeting accuracy was assessed as the Euclidean distance between the tip of the ablation probe and the tumor center (Target Positioning Error, TPE). Procedural efficiency was assessed as time efforts for tumor referencing and tumor targeting. RESULTS: In 6 animals, 124 targeting measurements were performed with an offset distance < 30 mm (clinically most feasible position), resulting in a mean TPE of 2.9 +/- 1.6 mm. No significant correlation between the TPE and different intrahepatic offset distances (range 21 to 61 mm, n = 365) was shown as long as the EM reference was placed within the liver. However, the mean TPE increased when placing the EM reference externally on the animal skin (p < 0.01). TPE was similar when targeting under continuous ventilation or in apnea (p = 0.50). Mean time for tumor referencing and navigated targeting was 6.5 +/- 3.8 minutes and 14 +/- 8 seconds, respectively. CONCLUSION: The proposed technique allows precise and efficient navigated positioning of ablation probes into liver tumors in the animal model. We introduce a simple approach suitable for combined ablation and TACE of HCC in a single treatment session. PMID- 29791522 TI - Improving the Management of Hereditary Angioedema. PMID- 29791521 TI - Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions. AB - OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of Sao Paulo School of Medicine, Hospital das Clinicas, Sao Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis. PMID- 29791523 TI - einstein (Sao Paulo) an innovative way to publish your research. PMID- 29791524 TI - All publishers are predatory - some are bigger than others. PMID- 29791525 TI - 2,3,8-Trisubstituted Quinolines with Antimalarial Activity. AB - Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P. falciparum NF54 (IC50 = 22 nM) and low cytotoxicity. We performed a detailed evaluation of the substituents to improve the metabolic stability and solubility liabilities of the original hit and identified derivatives with enhanced physicochemical and/or PK properties and that maintained biological activity. However the high potency was not retained on testing against drug resistant plasmodium strains. PMID- 29791526 TI - Geomorphology-based unit hydrograph models for flood risk management: case study in Brazilian watersheds with contrasting physiographic characteristics. AB - Heavy rainfall in conjunction with an increase in population and intensification of agricultural activities have resulted in countless problems related to flooding in watersheds. Among the techniques available for direct surface runoff (DSR) modeling and flood risk management are the Unit Hydrograph (UH) and Instantaneous Unit Hydrograph (IUH). This study focuses on the evaluation of predictive capability of two conceptual IUH models (Nash and Clark), considering their original (NIUH and CIUH) and geomorphological approaches (NIUHGEO and CIUHGEO), and their advantages over two traditional synthetics UH models - Triangular (TUH) and Dimensionless (DUH), to estimate DSR hydrographs taking as reference two Brazilian watersheds with contrasting geomorphological and climatic characteristics. The main results and conclusions were: i) there was an impact of the differences in physiographical characteristics between watersheds, especially those parameters associated with soil; the dominant rainfall patterns in each watershed had an influence on flood modeling; and ii) CIUH was the most satisfactory model for both watersheds, followed by NIUH, and both models had substantial superiority over synthetic models traditionally employed; iii) although geomorphological approaches for IUH had performances slightly better than TUH and DUH, they should not be considered as standard tools for flood modeling in these watersheds. PMID- 29791527 TI - Characteristics of women who do not consult a doctor: a population-based study. AB - OBJECTIVE To analyze the prevalence of not consulting a doctor within a year. METHODS Cross-sectional population-based study, including women aged 20-60 years, living in the urban area of Sao Leopoldo, state of Rio Grande do Sul, in 2015. The association between variables and outcome was assessed using prevalence ratios and 95% confidence intervals (95%CI). The adjusted analysis was performed using Poisson regression with robust variance. RESULTS Among the 1,127 women participating in the study, 954 (84.6%, 95%CI 82.5-86.7) reported having consulted a physician in the year prior to the interview, 173 (15.4%, 95%CI 13.2 17.5) did not. Women belonging to lower income classes D and E, younger, and smokers had higher prevalences of no medical visits. The participants with hypertension had a higher prevalence of consultations. CONCLUSIONS There was no expected evolution in the local health system, despite the emergence of the policies implemented in this period. It is necessary to provide care for those in less favored socioeconomic conditions and for younger women. PMID- 29791528 TI - Offer of primary care services and detection of tuberculosis incidence in Brazil. AB - OBJECTIVE To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35- -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41-3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48 2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98 2.76). CONCLUSIONS The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases. PMID- 29791529 TI - Prevalence and correlates of insufficient physical activity in school adolescents in Peru. AB - OBJECTIVE To assess the prevalence and correlates of insufficient physical activity in adolescents in Peru. METHODS We used a self-administered questionnaire developed from Global school-based Student Health Survey to collect information from secondary school students in North Lima and Callao in 2015. We carried out Poisson regression with robust variance using generalized linear models to estimate the crude and adjusted prevalence ratios (APR) with 95% confidence intervals (95%CI) of insufficient physical activity for its correlates. RESULTS We have found that 78% of the adolescents did not meet the global recommendation of the World Health Organization on physical activity in the last week before the survey. Female respondents (APR = 1.13, 95%CI 1.04 1.21), respondents who perceived themselves as overweight (APR = 1.10, 95%CI 1.03 1.18), and respondents who consumed insufficient vegetables and fruits [no vegetables (APR = 1.30, 95%CI 1.06-1.59), no fruits (APR = 1.15, 95%CI 1.00-1.31) as compared to those who consumed >= 2 servings every day in the last seven days] were more likely to report insufficient physical activity. Adolescents who worked after school (APR = 0.92, 95%CI 0.84-0.99), had physical education classes five times per week (APR = 0.94, 95%CI 0.88-0.99), and had parental supervision (APR = 0.92, 95%CI 0.87-0.98) were less likely to report insufficient physical activity. CONCLUSIONS Sex, work after school, perceived body weight, physical education class, parental support, and healthy dietary behaviors were associated with insufficient physical activity. Attempts to improve physical activity should look for ways to enhance leisure-time physical activity, parental support, physical education classes, healthy dietary behaviors, and normal body weight maintenance in adolescents with integrated efforts from the family and school. PMID- 29791530 TI - Consumption of vegetables and their relation with ultra-processed foods in Brazil. AB - OBJECTIVE To characterize the household purchase and the individual consumption of vegetables in Brazil and to analyze their relation with the consumption of ultra-processed foods. METHODS We have used data on the purchase of food for household consumption and individual consumption from the 2008-2009 Brazilian Household Budget Survey. The Brazilian Household Budget Survey studied the purchase of food of 55,970 households and the food consumption of 34,003 individuals aged 10 years and over. The foods of interest in this study were vegetables (excluding roots and tubers) and ultra-processed foods. We have described the amount of vegetables (grams) purchased and consumed by all Brazilians and according to the quintiles of caloric intake of ultra-processed food. To this end, we have calculated the crude and predicted values obtained by regression models adjusted for sociodemographic variables. We have analyzed the most commonly purchased types of vegetables (% in the total amount) and, in relation to individual food consumption, the variety of vegetables consumed (absolute number), the participation (%) of the types of culinary preparations based on vegetables, and the time of consumption. RESULTS The adjusted mean household purchase of vegetables was 42.9 g/per capita/day. The adjusted mean individual consumption was 46.1 g. There was an inverse relation between household purchase and individual consumption of vegetables and ultra-processed foods. Ten types of vegetables account for more than 80% of the total amount usually purchased. The variety consumed was, on average, 1.08 type/per capita/day. Approximately 60% of the vegetables were eaten raw, and the amount consumed at lunch was twice that consumed at dinner; individuals with higher consumption of ultra-processed foods tended to consume even less vegetables at dinner. CONCLUSIONS The consumption of vegetables in Brazil is insufficient, and this is worse among individuals with higher consumption of ultra-processed foods. The most frequent habit was to consume raw vegetables at lunch and with limited variety. PMID- 29791532 TI - Meanings of HIV/AIDS prevention and sexuality for young Catholics. AB - OBJECTIVE To analyze the the social representations of young Catholics about HIV/AIDS prevention and sexuality. METHOD Mixed study, based on the theory of social representations, held in 2015 with 84 young Catholics participating in the group "World Youth Day" on Facebook. The data were collected through the technique of free association of words and in-depth interview. For the information analysis, the software Tri-Deux-Mots and Alceste were used. RESULTS Sexuality is processed in the representational field of young people as being associated with the sexual practice. In turn, the prevention of HIV, a phenomenon represented as intrinsic to sexuality, occurs through the use of condoms or fidelity within marriage. CONCLUSION Young Catholics represent the prevention of HIV/AIDS as a transverse phenomenon to sexuality, whose sexual practices are anchored both in hegemonic and progressive discourses. PMID- 29791533 TI - Complementary therapies as resources for mental health in Primary Health Care. AB - OBJECTIVE To verify the knowledge of Primary Care professionals about Integrative and Complementary Practices (PIC - "Praticas Integrativas e Complementares") and if they perceive these Practices as a care resource in Mental Health. METHOD Quantitative study carried out with 70 professionals from a Basic Unit of Health in the city of Sao Paulo between May and June of 2016. The data were collected through a questionnaire elaborated by the researchers. For statistical analysis, the frequency distribution of the variables and the Fisher test were considered. RESULTS The professionals said that they were aware of some PIC (73.9%), that users of the service with Mental Health issues would benefit from them (94.2%), that they would like to receive training (91.3%), and that they consider the practices a possible resource for care in Mental Health (92.8%). CONCLUSION The professionals' knowledge needs to be deepened. Still, they consider PIC as a resource for Mental Health in Primary Care. PMID- 29791534 TI - Biosafety in beauty centers: knowledge and practices in a state capital in Northeast Brazil. AB - OBJECTIVE To evaluate the knowledge and biosafety practices adopted by professionals of the beauty segment. METHODS Descriptive study, of survey type. 238 professionals of the beauty segment were interviewed between August 2014 and 2015. The variables were expressed by means of absolute and relative frequencies, as well as average and standard deviation. RESULTS 62.6% of the interviwed professionals reported having had contact with blood from customers when they were not wearing gloves; 74.4% said they washed their hands before and after each service, and only 16.8% of the respondents reported reusing nonsterilizable materials. None of them was able to inform the correct number of sets of tools needed , and 32.8% of the respondents did not use Personal Protective Equipment during their work activities. CONCLUSIONS The most frequently reported diseases associated with the risk of infection and transmission in the work activities were viral hepatitis, HIV and fungi. Regarding the biosafety procedures adopted, autoclave is the least used method for sterilizing devices. PMID- 29791531 TI - Educational interventions in health services and oral health: systematic review. AB - OBJECTIVE To analyze the effectiveness of educational interventions performed in health services in the improvement of clinical behaviors and outcomes in oral health. METHODS We have carried out a systematic review of the literature searching the PubMed, Lilacs, and SciELO databases. We have included studies that have investigated interventions performed by health professionals working in health services and who have used educational actions as main approach to improve behavioral and clinical outcomes in oral health. RESULTS The search amounted to 832 articles and 14 of them met all the inclusion criteria. Five studies have only exclusively evaluated the effectiveness of interventions on caries reduction, three have exceptionally evaluated oral health behaviors, and the other articles have evaluated the effectiveness of interventions for both clinical outcomes (dental caries and periodontal conditions) and behaviors in oral health. Most of the studies (n = 9) were based on randomized controlled trials; the other ones have evaluated before and after the intervention. Five studies have reported a significant reduction of dental caries, and five of the six studies evaluating behavioral outcomes have found some positive change. CONCLUSIONS Most studies evaluating behavioral and periodontal outcomes have shown significant improvements in favor of interventions. All studies evaluating caries have shown a reduction in new lesions or cases of the disease in the groups receiving the interventions, although only five of the eleven articles have found a statistically significant difference. Educational interventions carried out by health professionals in the context of their practice have the potential to promote oral health in the population. PMID- 29791535 TI - Safe patient care in the preparation and administration of medicines. AB - OBJECTIVE To evaluate the compliance with the assistance and the adhesion of nursing professionals for the safe administration of drugs in an Intensive Care Unit of a public hospital in Sergipe, Brazil. METHOD Quantitative, descriptive and cross-sectional study carried out by direct non-participant observation. Data collection performed in 2015. Non-probabilistic sample, for convenience, consisting in the observation of 557 doses of prepared and administered drugs. For data analysis, descriptive statistics were used for data analysis. RESULTS The items classified as safe care were: correct via (85.7%) and correct form (100%). The items classified as undesirable care were: correct patient (33.3%), correct medication (66.67%), correct dose (50%), correct register (33.33%), correct orientation (0%), and correct time (50%). CONCLUSION The practice was evaluated according to Carte's positivity index as undesirable care, considering that six of the eight items had low adhesion. The found weaknesses compromised the whole process of drug administration. PMID- 29791536 TI - The parental care partnership in the view of parents of children with special health needs. AB - OBJECTIVE To understand how the care partnership was experienced by parents of children with special healthcare needs. METHOD Qualitative, descriptive and exploratory study, carried out from December 2013 to February 2014. The method used was the narrative. The population corresponded to parents of children admitted to a medical service of a Pediatric Hospital in Portugal. The sample consisted of 10 parents. The data collection included the sociodemographic characterization and the etnobiografic orientation interview. Once transcribed, the interviews yielded 10 narratives of partnership experiences between the parents and the nursing team. RESULTS It was noted, as partnership opportunities, the training of parents and the collaborative decision-making, established in a dynamic, unique and ongoing relational process. CONCLUSION The opportunities for partnership are key assumptions for the care delivery focusing on the child and on the parents as their resources. PMID- 29791537 TI - The family of the child with cancer: socioeconomic needs. AB - OBJECTIVE To identify the socioeconomic variables which influence the families of the child with cancer. METHODS Quantitative, descriptive, correlational research with 128 families of children with cancer. Three instruments were used: "Questionnaire assessing the impact on the family of children with cancer", "Social Support Satisfaction Scale", and "Graffar Scale". RESULTS Families report increased economic spending due to the disease, with the displacements to hospital and medication. The loss of income by one of the parents also exacerbates the economic impact of the disease. Families with greater support needs and lower social support present greater economic impact. CONCLUSION The social support assumes an important role in the decrease of the economic needs incited by the disease. Nurses must identify the economic needs of the families and become part of the support network of them, being a source of support so they can strengthen themselves in caring. PMID- 29791538 TI - Complications in pregnancy in women aged 35 or older. AB - OBJECTIVE To verify the frequency and factors associated with complications during pregnancy and the association between complications with premature birth and type of delivery in pregnant women aged 35 years or older. METHODS This is a cross-sectional study based on the records of pregnant women admitted between January and July 2012, totalling 430 pregnant women. To identify possible factors associated with complications during pregnancy, data were subjected to univariate analysis using the Poisson regression model. The chi-squared test was used to study the association of complications with premature birth ad type of delivery. RESULTS Complications occurred in 77.7% of the cases. Complications in pregnancy as an explanatory variable for premature birth (p < 0.001) and C-section (p = 0.002) was statistically significant. CONCLUSION The factors younger age, the absence of prenatal care, and the non-occurrence of morbidity prior to gestation were associated with complications in pregnancy. PMID- 29791539 TI - Therapeutic communication in the interaction between health workers and hypertensive patients in the family health strategy. AB - OBJECTIVE To analyze the therapeutic communication in the interaction between health professionals and hypertensive patients in the Family Health Strategy. METHODS Descriptive study with qualitative approach. The sample consisted of 14 hypertensive patients and two health professionals of the Family Health Strategy (ESF - "Estrategia Saude Familia") in a city of the state of Ceara, Brazil, in 2016. In the data collection, a checklist was used for non-participant systematic observation containing the strategies of therapeutic communication, namely: expression, clarity, validation, and a field diary, being these subjected to content analysis. RESULTS It was noted that ESF professionals do not adequately use therapeutic communication, indicating the need of investment in this device, which acts as a bridge for users, enhances care practices and opens paths that instrumentalize interpersonal relationships. CONCLUSIONS It was realized that health professionals are not fully exploring therapeutic communication strategies, therefore being necessary to develop skills to use these techniques correctly when caring for hypertensive patients. PMID- 29791540 TI - Strengthening the leadership of the Commission on Education-Service Integration for permanent health education. AB - OBJECTIVE To know the performance of universities in the Permanent Commission of Education-Service Integration in the West Region of Santa Catarina, with a view to strengthening its role in the development of continuing education initiatives in health. METHODOLOGY Convergent Care Research developed in the first half of 2014, involving interviews with university professors, workshops with the Technical Board of the Permanent Commission of Education-Service Integration and participation in meeting with representatives of the Region. RESULTS Three categories were identified concerning the role of universities in the development of health education actions, as well as the role of the Commission as a favourable space to the articulation of these institutions. FINAL THOUGHTS Universities play a key role in the development of permanent education actions in health, considering the reality of the territory and services, as well as demands and potential of the actors involved, which favours the teaching-service integration in the Region. PMID- 29791541 TI - Maintenance of tobacco withdrawal by former smokers: a phenomenological study. AB - OBJECTIVE To understand the experience of former smokers maintaining tobacco abstinence. METHODS Qualitative research using the theoretical-methodological reference of the Social Phenomenology, as defined by Alfred Schutz. The phenomenological interview was carried out in 2016 with 12 former smokers from a city in the state of Minas Gerais, Brazil. The statements were organized into categories and discussed based on the literature. RESULTS The maintenance of tobacco abstinence was revealed in the categories: "Health, sociability, and financial gains"; "Living with the urge to smoke and with the increase of body weight"; "Self-determination and use of replacement strategies"; and "Staying away from cigarettes." CONCLUSIONS These results alert health professionals to the need to provide support to former smokers so they can remain smoke-free. This implies considering not only the negative effects of the tobacco abstinence, but also the social context in which former smokers are inserted that might have an impact on the maintenance or not of the cigarette withdrawal. PMID- 29791543 TI - Rapidly growing pulmonary ground-glass nodule caused by metastatic melanoma lacking uptake on 18F-FDG PET-CT. PMID- 29791542 TI - Impact of smoking on sputum culture conversion and pulmonary tuberculosis treatment outcomes in Brazil: a retrospective cohort study. AB - OBJECTIVE: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. METHODS: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. RESULTS: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). CONCLUSIONS: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never smokers, as was the probability of a poor treatment outcome. PMID- 29791544 TI - Tuberculosis: where are we? PMID- 29791545 TI - Knowledge and perceptions of tuberculosis transmission and prevention among physicians and nurses in three Brazilian capitals with high incidence of tuberculosis. PMID- 29791546 TI - Rapid molecular test for tuberculosis: impact of its routine use at a referral hospital. AB - OBJECTIVE: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. METHODS: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octavio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. RESULTS: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. CONCLUSIONS: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients. PMID- 29791548 TI - The role of the Brazilian Tuberculosis Research Network in national and international efforts to eliminate tuberculosis. PMID- 29791547 TI - Predictors of mortality among intensive care unit patients coinfected with tuberculosis and HIV. AB - OBJECTIVE: To identify factors predictive of mortality in patients admitted to the ICU with tuberculosis (TB)/HIV coinfection in the Manaus, Amazon Region. METHODS: This was a retrospective cohort study of TB/HIV coinfected patients over 18 years of age who were admitted to an ICU in the city of Manaus, Brazil, between January of 2011 and December of 2014. Sociodemographic, clinical, and laboratory variables were assessed. To identify factors predictive of mortality, we employed a Cox proportional hazards model. RESULTS: During the study period, 120 patients with TB/HIV coinfection were admitted to the ICU. The mean age was 37.0 +/- 11.7 years. Of the 120 patients evaluated, 94 (78.3%) died and 62 (66.0%) of those deaths having occurred within the first week after admission. Data on invasive mechanical ventilation (IMV) and ARDS were available for 86 and 67 patients, respectively Of those 86, 75 (87.2%) underwent IMV, and, of those 67, 48 (71.6%) presented with ARDS. The factors found to be independently associated with mortality were IMV (p = 0.002), hypoalbuminemia (p = 0.013), and CD4 count < 200 cells/mm3 (p = 0.002). CONCLUSIONS: A high early mortality rate was observed among TB/HIV coinfected ICU patients. The factors predictive of mortality in this population were IMV, hypoalbuminemia, and severe immunosuppression. PMID- 29791549 TI - Nontuberculous mycobacterial lung disease in a high tuberculosis incidence setting in Brazil. AB - OBJECTIVE: The incidence of lung disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. In Brazil, there are few studies about nontuberculous mycobacterial lung disease (NTMLD), and its prevalence is yet to be known. Our objective was to determine the specific etiology of the disease in the state of Rio Grande do Sul, Brazil, as well as the frequency and diversity of NTM species in our sample of patients. METHODS: This is a retrospective analysis of the medical records of patients diagnosed with NTMLD treated in a referral center located in the city of Porto Alegre, Brazil, between 2003 and 2013. RESULTS: Our sample comprised 100 patients. The most prevalent NTM species were Mycobacterium avium complex (MAC), in 35% of the cases; M. kansasii, in 17%; and M. abscessus, in 12%. A total of 85 patients had received previous treatment for tuberculosis. Associated conditions included structural abnormalities in the lungs, such as bronchiectasis, in 23% of the cases; COPD, in 17%; and immunosuppressive conditions, such as AIDS, in 24%. CONCLUSIONS: MAC and M. kansasii were the most prevalent species involved in NTMLD in the state, similarly to what occurs in other regions of Brazil. Data on regional epidemiology of NTMLD, its specific etiology, and associated conditions are essential to establish appropriate treatment, since each species requires specific regimens. Most patients with NTMLD had received previous tuberculosis treatment, which might lead to development of resistance and late diagnosis. PMID- 29791550 TI - Inclusion and exclusion criteria in research studies: definitions and why they matter. PMID- 29791551 TI - Eliminating tuberculosis in Latin America: making it the point. PMID- 29791553 TI - Epidemiological aspects, clinical manifestations, and prevention of pediatric tuberculosis from the perspective of the End TB Strategy. AB - Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy. PMID- 29791554 TI - Chest X-ray and chest CT findings in patients diagnosed with pulmonary tuberculosis following solid organ transplantation: a systematic review. AB - The objective of this systematic review was to select articles including chest X ray or chest CT findings in patients who developed pulmonary tuberculosis following solid organ transplantation (lung, kidney, or liver). The following search terms were used: "tuberculosis"; "transplants"; "transplantation"; "mycobacterium"; and "lung". The databases used in this review were PubMed and the Brazilian Biblioteca Virtual em Saude (Virtual Health Library). We selected articles in English, Portuguese, or Spanish, regardless of the year of publication, that met the selection criteria in their title, abstract, or body of text. Articles with no data on chest CT or chest X-ray findings were excluded, as were those not related to solid organ transplantation or pulmonary tuberculosis. We selected 29 articles involving a collective total of 219 patients. The largest samples were in studies conducted in Brazil and South Korea (78 and 35 patients, respectively). The imaging findings were subdivided into five common patterns. The imaging findings varied depending on the transplanted organ in these patients. In liver and lung transplant recipients, the most common pattern was the classic one for pulmonary tuberculosis (cavitation and "tree-in-bud" nodules), which is similar to the findings for pulmonary tuberculosis in the general population. The proportion of cases showing a miliary pattern and lymph node enlargement, which is most similar to the pattern seen in patients coinfected with tuberculosis and HIV, was highest among the kidney transplant recipients. Further studies evaluating clinical data, such as immunosuppression regimens, are needed in order to improve understanding of the distribution of these imaging patterns in this population. PMID- 29791552 TI - Risk factors for tuberculosis: diabetes, smoking, alcohol use, and the use of other drugs. AB - Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions. PMID- 29791555 TI - Who are the patients with tuberculosis who are diagnosed in emergency facilities? An analysis of treatment outcomes in the state of Sao Paulo, Brazil. AB - OBJECTIVE: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. METHODS: We analyzed data from the Sao Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. RESULTS: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. CONCLUSIONS: In the state of Sao Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement. PMID- 29791556 TI - Clinical aspects in patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex, in the Brazilian Amazon. AB - OBJECTIVE: To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). METHODS: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. RESULTS: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. CONCLUSIONS: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM. PMID- 29791558 TI - Giant pulmonary artery aneurysm in a patient with schistosomiasis-associated pulmonary arterial hypertension. PMID- 29791557 TI - New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis. AB - Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported. PMID- 29791559 TI - Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis. AB - OBJECTIVE: To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. METHODS: This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. RESULTS: We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. CONCLUSIONS: The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts. PMID- 29791560 TI - Tuberculosis series. PMID- 29791561 TI - Lymph node calcifications. PMID- 29791562 TI - Critical analyses when modeling tree biomass to ensure additivity of its components. AB - It is presented the theme additivity of biomass of tree components. To evaluate and discuss this context, experimental information collected in forests of Acacia mearnsii De Wild. was used. Equations for components (stem and crown) and total biomass were fitted by means of two procedures: 1) generalized nonlinear least squares and 2) weighted-nonlinear seemingly unrelated regressions. Analyzing the performance of the estimators, it can be concluded that the two tested procedures are equivalent. On the other hand, this conclusion differs when evaluated the consistency and efficiency of the estimators. Fitting equations for the components and for the total biomass by an independent way is not realistic, because from a biological point of view the estimates of biomass are inconsistent, i.e., are not additive. The biomass estimates of the components and of the total, resulting from equations adjusted by means of systems of equations, provided narrower confidence intervals in relation to the equations adjusted independently, and is therefore more efficient. The second procedure presents better biological properties and statistics to estimate allometric equations for biomass of the components and for the total when compared with the independent estimation, thus it should be the method to be used. PMID- 29791563 TI - Insects galls of Pantanal areas in the State of Mato Grosso do Sul, Brazil: characterization and occurrence. AB - Two Pantanal areas were investigated in Corumba, Mato Grosso do Sul. The field works were carried out in five trails, in August and December/2011 and April/2012. Seventy-six gall morphotypes were found in 52 host plants, 22 of them were identified at species level and 30 at genus. Fabaceae, Myrtaceae and Sapindaceae were the plant families with the greatest richness of gall. Leaves were the plant organ with the greatest gall richness. Six gall shapes were found globoid, lenticular, fusiform, cylindrical, conical, and marginal roll. The three first were the most common. Five colors were observed - green, brown, red, yellow, and black. Green and brown predominated. Most were glabrous and one chambered. These features have been indicated in several Brazilian biomes. Diptera (Cecidomyiidae) were the most frequent gallers. The associated fauna comprised parasitoids (Eulophidae, Braconidae, Eupelmidae, Eurytomidae, Platygastridae, and Pteromalidae), inquilines (Cecidomyiidae: Trotteria Kieffer, 1902, Hymenoptera: Tanaostigmoides Ashmead, 1896, Hemiptera, Lepidoptera and Thysanoptera) and predators (Pseudoscorpionida: Olpiolum medium Beier, 1931, Cecidomyiidae: Lestodiplosini and Hymenoptera: Formicidae). Parasitoids were the most frequent. Multiparatism was observed. Our data represent the first contribution to the knowledge of the associated fauna in the Pantanal. PMID- 29791564 TI - Morphology and morphometry of upland lakes over lateritic crust, Serra dos Carajas, southeastern Amazon region. AB - High-resolution satellite images, digital elevation models, bathymetric and sedimentological surveys coupled with statistical analysis were used to understand the physical environment and discuss their influence on water quality of the five upland lakes of Serra Sul dos Carajas, southeast Amazonia. The lakes have mid-altitude ranges (elevation), very small (catchment) and shallow to very shallow (central basins). Based on the length, area and volume, Violao and TI (Tres Irmas)-3 lakes may present large vertical movements of the water due to wind action and weakly stratified waters. Trophic conditions based on depth and shore development (Ld) parameters must be used with caution, since Amendoim Lake is relatively deep, but it is oligotrophic to ultra-oligotrophic. Ld values suggest that the lakes are circular to subcircular and are likely formed by solution process, as also suggested by volume development. TI-2 Lake is only presenting convex central basin and has highest dynamic ratio (DR), thus it may have high sedimentation and erosion rates. Based on the relationship between studied parameters, morphometric index and DR likely influence temperature and dissolved oxygen of waters of TI-2 Lake due to its depth profile and wind-induced surface mixing. Nevertheless, water quality parameters are controlled by catchment characteristics of the lakes. PMID- 29791565 TI - A giant on the ground: another large-bodied Atractus (Serpentes: Dipsadinae) from Ecuadorian Andes, with comments on the dietary specializations of the goo-eaters snakes. AB - Body-size is significantly correlated with the number of vertebrae (pleomerism) in multiple vertebrate lineages, indicating that somitogenesis process is an important factor dictating evolutionary change associated to phyletic allometry and, consequently, species fitness and diversification. However, the role of the evolution of extreme body sizes (dwarfism and gigantism) remains elusive in snakes, mainly with respect to postnatal ontogeny in dietary preferences associated with evolution of gigantism in many lineages. We described herein a new species in the highly diversified and species-rich genus Atractus on the basis of four specimens from the southeastern slopes of the Ecuadorian Andes. The new species is morphologically similar and apparently closely related to two other allopatric giant congeners (A. gigas and A. touzeti), from which it can be distinguished by their distinct dorsal and ventral coloration, the number of supralabial and infralabial scales, the number of maxillary teeth, and relative width of the head. In addition, we discuss on the ontogenetic trajectories hypotheses and dietary specializations related to evolution of gigantism in the goo-eaters genus Atractus. PMID- 29791566 TI - Cytidine-phosphate-guanosine oligodeoxynucleotides in combination with CD40 ligand decrease periodontal inflammation and alveolar bone loss in a TLR9 independent manner. AB - : Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. OBJECTIVE: This study aimed to explore whether such effect is dependent on TLR9 signaling. MATERIAL AND METHODS: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses. We determined B cell numbers using a hemocytometer at 24 h and 48 h. Percentages of CD1dhiCD5+ B cells were detected by flow cytometry. Interleukin-10 (IL-10) mRNA expression and protein secretion were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and by ELISA, respectively. The silk ligature was tied around the maxillary second molars for 14 days, during which the CpG+CD40L mixture or PBS was injected into palatal gingiva on days 3, 6, and 9. RESULTS: For both WT and TLR9 KO mice, CpG significantly induced B cell proliferation, increased IL-10 mRNA expression and protein secretion of IL-10 but reduced CD1dhiCD5+ B cells population; local injection of CpG+CD40L mixture significantly decreased alveolar bone loss and the number of TRAP-positive cells adjacent to the alveolar bone surface, and significantly increased the gingival mRNA expression of IL-10 and decreased RANKL and IFN-gamma mRNA expression. CONCLUSIONS: These results indicated that CpG plus CD40L decreased periodontal inflammation and alveolar bone loss in a TLR9-independent manner in ligature induced experimental periodontitis. PMID- 29791567 TI - Immunohistological study of the effect of vascular Endothelial Growth Factor on the angiogenesis of mature root canals in rat molars. AB - Tissue bioengineering has been applied to Endodontics to seek a more biological treatment. The presence of blood vessels is crucial for cell nutrition during tissue formation. Objective This study analysed the application of vascular endothelial growth factor (VEGF) in the angiogenesis of mature root canals. Material and methods Upper first molars of twelve 13-week old Wistar male rats were used. The root pulp of the mesiobuccal canal was removed and the root canal instrumented with K-files up to size #25. Periapical bleeding was induced into the root canal by introducing a #15 K-file beyond the apex. The teeth on the right side of the arch were filled up with blood clot (G1), whereas those on the left side were filled up with blood clot plus 50 ng/ml of VEGF (G2). Teeth were sealed with light-curing glass-ionomer cement and the animals were sacrificed after 60 days. The maxilla was dissected and fixed before obtaining serial sections for histological processing with haematoxylin-eosin (HE) and immunohistochemical factor-VIII. Immunohistochemical labelling was evaluated using scores for statistical analysis. Results Immunohistological analysis demonstrated the presence of angiogenesis in both groups, but with higher angiogenic maturation in G2 during the experimental period (p<0.05). HE staining showed connective tissue with absence of odontoblasts in all specimens. Conclusions It can be concluded that it is possible to obtain angiogenesis in mature root canals with or without the use of VEGF, although the latter tends to accelerate blood vessel formation. PMID- 29791569 TI - Solubility, porosity and fluid uptake of calcium silicate-based cements. AB - OBJECTIVE: To evaluate the absorption/fluid uptake, solubility and porosity of White mineral trioxide aggregate (MTA) Angelus, Biodentine (BIO), and zinc oxide eugenol (ZOE). MATERIAL AND METHODS: Solubility was evaluated after immersion in distilled water for 7 and 30 days. Porosity was evaluated using digital inverted microscope, scanning electron microscope (SEM) and micro-computed tomography (micro-CT). For the fluid uptake test, specimens were immersed in Hank's balanced salt solution (HBSS) for 1, 7, 14 and 28 days. Fluid absorption, solubility and porosity of the materials were measured after each period. Statistical evaluation was performed using one-way analysis of variance (ANOVA) and Tukey tests, with a significance level at 5%. RESULTS: After 7 and 30 days, BIO showed the highest solubility (p<0.05). All methods demonstrated that MTA had total porosity higher than BIO and ZOE (p<0.05). Micro-CT analysis showed that MTA had the highest porosity at the initial period, after its setting time (p<0.05). After 7 and 30 days, ZOE had porosity lower than MTA and BIO (p<0.05). Absorption was similar among the materials (p>0.05), and higher fluid uptake and solubility were observed for MTA in the fluid uptake test (p<0.05). CONCLUSIONS: BIO had the highest solubility in the conventional test and MTA had higher porosity and fluid uptake. ZOE had lower values of solubility, porosity and fluid uptake. Solubility, porosity and fluid uptake are related, and the tests used provided complementary data. PMID- 29791568 TI - Assessing the association between hypoxia during craniofacial development and oral clefts. AB - Objectives To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods The study with the animal model used zebrafish embryos at 8 hours post fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p<0.0001). For the families, there was no under-transmitted allele among the affected progeny (p>0.05). Conclusion Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans. PMID- 29791571 TI - Better Technology, More Spending, Worse Outcomes. PMID- 29791570 TI - Osteoradionecrosis of the jaws: case series treated with adjuvant low-level laser therapy and antimicrobial photodynamic therapy. AB - BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. METHODS: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. RESULTS: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. CONCLUSION: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ. PMID- 29791573 TI - Infections in Heart Failure - Impact on Mortality. PMID- 29791572 TI - Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? AB - BACKGROUND: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. OBJECTIVE: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. METHODS: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) * (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) * (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. RESULTS: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. CONCLUSION: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders. PMID- 29791574 TI - Applicability of Longitudinal Strain of Left Ventricle in Unstable Angina. AB - BACKGROUND: Unstable angina (UA) is a common cause of hospital admission; risk stratification helps determine strategies for treatment. OBJECTIVE: To determine the applicability of two-dimensional longitudinal strain (SL2D) for the identification of myocardial ischemia in patients with UA. METHODS: Cross sectional, descriptive, observational study lasting 60 days. The sample consisted of 78 patients, of which fifteen (19.2%) were eligible for longitudinal strain analysis. The value of p < 0.05 was considered significant. RESULTS: The group of ineligible patients presented: a lower proportion of women, a higher prevalence of diabetes mellitus (DM), use of ASA, statins and beta-blockers and larger cavity diameters. The main causes of non-applicability were: presence of previous infarction (56.4%), previous CTA (22.1%), previous MRI (11.5%) or both (16.7%) and the presence of specific electrocardiographic abnormalities (12.8%). SL2D assessment revealed a lower global strain value in those with stenosis greater than 70% in some epicardial coronary arteries (17.1 [3.1] versus 20.2 [6.7], with p = 0.014). Segmental strain assessment showed an association between severe CX and RD lesions with longitudinal strain reduction of lateral and inferior walls basal segments; (14 [5] versus 21 [10], with p = 0.04) and (12.5 [6] versus 19 [8], respectively). CONCLUSION: There was very low SL2D applicability to assess ischemia in the studied population. However, the global strain showed a correlation with the presence of significant coronary lesion, which could be included in the UA diagnostic arsenal in the future. PMID- 29791576 TI - Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure. PMID- 29791575 TI - Primary Ventricular Fibrillation in a Patient with Mild Hypercalcemia. PMID- 29791577 TI - Speckle-Tracking Echocardiography - Ready for Use in Acute Coronary Syndrome? PMID- 29791578 TI - High-Intensity Interval Training for Early Post-Acute Myocardial Infarction - A Promising Approach for Rats, but what about Human Beings? PMID- 29791579 TI - Case 2/2018 - 73-Year-Old Male with Ischemic Cardiomyopathy, Cachexia and Shock. PMID- 29791580 TI - Influence of Aerobic Training on The Mechanics of Ventricular Contraction After Acute Myocardial Infarction: A Pilot Study. AB - The study of myocardial contractility, based on the new anatomical concepts that govern cardiac mechanics, represents a promising strategy of analysis of myocardial adaptations related to physical training in the context of post infarction. We investigated the influence of aerobic training on physical capacity and on the evaluation parameters of left ventricular contraction mechanics in patients with myocardial infarction. Thirty-one patients (55.1 +/- 8.9 years) who had myocardial infarction in the anterior wall were prospectively investigated in three groups: interval training group (ITG) (n = 10), moderate training group (MTG) n = 10) and control group (CG) (n = 10). Before and after 12 weeks of clinical follow-up, patients underwent cardiopulmonary exercise testing and cardiac magnetic resonance imaging. The trained groups performed supervised aerobic training on treadmill, in two different intensities. A statistically significant increase in peak oxygen uptake (VO2) was observed in the ITG (19.2 +/ 5.1 at 21.9 +/- 5.6 ml/kg/min, p < 0.01) and in the MTG 18.8 +/- 3.7 to 21.6 +/- 4.5 ml/kg/min, p < 0.01). The GC did not present a statistically significant change in peak VO2. A statistically significant increase in radial strain (STRAD) was observed in the CG: basal STRAD (57.4 +/- 16.6 to 84.1 +/- 30.9%, p < 0.05), medial STRAD (57.8 +/- 27, 9 to 74.3 +/- 36.1%, p < 0.05) and apical STRAD (38.2 +/- 26.0 to 52.4 +/- 29.8%, p < 0.01). The trained groups did not present a statistically significant change of the radial strain. The present study points to a potential clinical application of the parameters of ventricular contraction mechanics analysis, especially radial strain, to discriminate post-infarction myocardial adaptations between patients submitted or not to aerobic training programs. PMID- 29791581 TI - Simultaneous Dual Coronary Fistulas. PMID- 29791582 TI - Incidence of Atrial High-Rate Episodes in Chagas Disease Patients. PMID- 29791584 TI - Risk factors for early-onset ventilator-associated pneumonia in aneurysmal subarachnoid hemorrhage patients. AB - This study aimed to investigate the risk factors related to ventilator-acquired pneumonia (VAP) in aneurysmal subarachnoid hemorrhage (SAH) patients. From January 2011 to December 2015, a single-center retrospective study including 200 SAH patients requiring mechanical ventilation (MV) >=48 h was performed. The clinical data of these patients were collected and analyzed. The age range of the patients were 41-63 and 72 (36%) were male. The Glasgow coma scale score range was 5-15 and the Simplified Acute Physiology Score II range was 31-52. One hundred and forty-eight (74%) patients had a World Federation of Neurosurgeons (WNFS) score >=III. Aneurysm was secured with an endovascular coiling procedure in 168 (84%) patients and 94 (47%) patients presented VAP. Male gender (OR=2.25, 95%CI=1.15-4.45), use of mannitol (OR=3.02, 95%CI=1.53-5.94) and enteral feeding above 20 kcal.kg-1.day-1 (OR=2.90, 95%CI=1.26-6.67) after day 7 were independent factors for VAP. Patients with early-onset VAP had a longer duration of sedation (P=0.03), MV (P=0.001) and ICU length of stay (P=0.003) and a worse Glasgow Outcome Scale score (P<0.001), but did not have a higher death rate. PMID- 29791583 TI - What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day. AB - Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women's kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. PMID- 29791585 TI - Protective effect and mechanism of Lactobacillus on cerebral ischemia reperfusion injury in rats. AB - The present study was designed to investigate the protective effects and mechanism of inactivated lactobacillus (ILA) on cerebral ischemia reperfusion injury (CIRI) in rats. In this experiment, 30 male Sprague Dawley rats were randomly divided into control group, IRI groups, and ILA group. A middle cerebral artery occlusion and reperfusion model was prepared. The rats were killed after 24 hours of recovery of blood flow of cerebral ischemia resulting from 60-min occlusion. The cerebral infarction volume and neurological scores were assayed by staining and behavioral observation. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assayed by biochemical kits. Cell apoptosis was assayed by Tunnel and the Toll-like receptor (TLR)-4, IkB, and A20 were assayed by western blot. The neurobehavioral scores in IRI rats were significantly lower compared to the control group while ILA improved the neurobehavioral scores of the ILA groups. The cerebral infarction volume and neural cell apoptosis of rats in the ILA groups decreased significantly compared with those in the IRI group. In addition, MDA level in the ILA groups decreased whereas SOD activity increased compared to the IRI group. Moreover, ILA also inhibited the expression of TLR-4 and promoted the expression of IkB and A20. ILA inhibited the apoptosis of neural cells, decreased cerebral infarction volume, and reduced oxidative stress through inhibition of TLR-4/NF-kappa B signaling, improving neurobehavioral scores. Thus from the present study it was concluded that ILA has protective effect on CIRI. PMID- 29791587 TI - Association study of AFF1 rs340630 polymorphism with genetic susceptibility to rheumatoid arthritis in Chinese population. AB - This study was performed to examine whether the AF4/FMR2 family, member 1 (AFF1) rs340630 polymorphism is involved in the genetic background of rheumatoid arthritis (RA) in a Chinese population. Two different study groups of RA patients and controls (328 RA patients and 449 healthy controls in the first study group; 232 RA patients and 313 controls in the second study group) were included in our study. Overall, there was no significant difference in either genotype (P=0.71 and 0.64 in the first and second study group, respectively) nor allele (in the first study group: A vs G, P=0.65, OR=1.05, 95%CI=0.85-1.29; in the second study group: G vs A, P=0.47, OR=1.10, 95%CI=0.86-1.40) frequencies of AFF1 rs340630 polymorphism between RA patients and controls. Our study represents the first report assessing the association of AFF1 rs340630 polymorphism with RA risk. No significant evidence was found for the dominant or recessive models. Further case control studies with larger sample sizes and fine-mapping studies are needed to clarify the role of AFF1 in the genetic basis of RA. PMID- 29791586 TI - Hypoxia-induced hyperpermeability of rat glomerular endothelial cells involves HIF-2alpha mediated changes in the expression of occludin and ZO-1. AB - This study aimed to investigate the role of hypoxia-inducible factor-2alpha (HIF 2alpha) in the expression of tight junction proteins and permeability alterations in rat glomerular endothelial cells (rGENCs) under hypoxia conditions. The expression level of HIF-2alpha and tight junction proteins (occludin and ZO-1) in rGENCs were examined following 5% oxygen density exposure at different treatment times. HIF-2alpha lentivirus transfection was used to knockdown HIF-2alpha expression. Cells were divided into four groups: 1) control group (rGENCs were cultured under normal oxygen conditions), 2) hypoxia group (rGENCs were cultured under hypoxic conditions), 3) negative control group (rGENCs were infected with HIF-2alpha lentivirus negative control vectors and cultured under hypoxic conditions), and 4) Len group (rGENCs were transfected with HIF-2alpha lentivirus and cultured under hypoxic conditions). The hypoxia, negative control, and Len groups were kept in a hypoxic chamber (5% O2, 5% CO2, and 90% N2) for 24 h and the total content of occludin and ZO-1, and the permeability of rGENCs were assessed. With increasing hypoxia time, the expression of HIF-2alpha gradually increased, while the expression of occludin decreased, with a significant difference between groups. ZO-1 expression gradually decreased under hypoxia conditions, but the difference between the 24 and 48 h groups was not significant. The permeability of cells increased following 24-h exposure to hypoxia compared to the control group (P<0.01). The knockdown of HIF-2alpha expression significantly increased occludin and ZO-1 content compared with hypoxia and negative control groups (P<0.01), while permeability was reduced (P<0.01). Hypoxia increased HIF-2alpha content, inducing permeability of rGENCs through the reduced expression of occludin and ZO-1. PMID- 29791588 TI - MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment. AB - Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221 3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA 34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA 451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants. PMID- 29791589 TI - Non-invasive messenger RNA transcriptional evaluation in human kidney allograft dysfunction. AB - The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670-0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment. PMID- 29791590 TI - lncRNA CCAT1 promotes cell proliferation, migration, and invasion by down regulation of miR-143 in FTC-133 thyroid carcinoma cell line. AB - Thyroid cancer is a common malignant tumor. Long non-coding RNA colon cancer associated transcript 1 (lncRNA CCAT1) is highly expressed in many cancers; however, the molecular mechanism of CCAT1 in thyroid cancer remains unclear. Hence, this study aimed to investigate the effect of CCAT1 on human thyroid cancer cell line FTC-133. FTC-133 cells were transfected with CCAT1 expressing vector, CCAT1 shRNA, miR-143 mimic, and miR-143 inhibitor, respectively. After different treatments, cell viability, proliferation, migration, invasion, and apoptosis were measured. Moreover, the regulatory relationship of CCAT1 and miR 143, as well as miR-143 and VEGF were tested using dual-luciferase reporter assay. The relative expressions of CCAT1, miR-143, and VEGF were tested by qRT PCR. The expressions of apoptosis-related factors and corresponding proteins in PI3K/AKT and MAPK pathways were analyzed using western blot analysis. The results suggested that CCAT1 was up-regulated in the FTC-133 cells. CCAT1 suppression decreased FTC-133 cell viability, proliferation, migration, invasion, and miR-143 expression, while it increased apoptosis and VEGF expression. CCAT1 might act as a competing endogenous RNA (ceRNA) for miR-143. Moreover, CCAT1 activated PI3K/AKT and MAPK signaling pathways through inhibition of miR-143. This study demonstrated that CCAT1 exhibited pro-proliferative and pro-metastasis functions on FTC-133 cells and activated PI3K/AKT and MAPK signaling pathways via down regulation of miR-143. These findings will provide a possible target for clinical treatment of thyroid cancer. PMID- 29791591 TI - Searching for the best real-time RT-PCRs to detect Zika virus infections: the importance of comparing several protocols. AB - Clinical manifestations of Zika, dengue, and chikungunya virus infections are very similar, making it difficult to reach a diagnosis based only on clinical grounds. In addition, there is an intense cross-reactivity between antibodies directed to Zika virus and other flaviviruses, and an accurate Zika diagnosis is best achieved by real-time RT-PCR. However, some real-time RT-PCR show better performance than others. To reach the best possible Zika diagnosis, the analytic sensitivity of some probe-based real-time RT-PCR amplifying Zika virus RNA was evaluated in spiked and clinical samples. We evaluated primers and probes to detect Zika virus, which had been published before, and tested sensitivity using serum spiked and patient samples by real-time RT-PCR. When tested against spiked samples, the previously described primers showed different sensitivity, with very similar results when samples from patients (serum and urine) were analyzed. Real time RT-PCR designed to amplify Zika virus NS1 showed the best analytical sensitivity for all samples. PMID- 29791592 TI - Pathogenesis of gallbladder adenomyomatosis and its relationship with early-stage gallbladder carcinoma: an overview. AB - The exact pathogenesis of gallbladder adenomyomatosis is still lacking and some controversies over its diagnosis and treatment exist. Originally recognized as a precancerous lesion, adenomyomatosis is currently recognized by recent studies as a benign alteration of the gallbladder that is often associated with cholecystitis and cholecystolithiasis. Gallbladder carcinoma is an extremely malignant disease with a 5-year survival rate of less than 5%. Therefore, it is important to diagnose, differentiate, and confirm the relationship between adenomyomatosis and early-stage gallbladder carcinoma. However, the early clinical symptoms of adenomyomatosis are extremely similar to those of gallbladder stones and cholecystitis, increasing the difficulty to identify and treat this disease. This article summarizes the research progress on gallbladder adenomyomatosis, aiming to improve the understanding of the pathogenesis of adenomyomatosis and further provide insight for its clinical diagnosis and treatment. PMID- 29791593 TI - Efficacy of cognitive behavioral therapy in children and adolescents with insomnia: a systematic review and meta-analysis. AB - Insomnia is highly prevalent in children and adolescents. However, the efficacy of cognitive behavioral therapy for insomnia (CBT-i) in children and adolescents remains controversial. Therefore, this systematic review and meta-analysis aimed to assess the efficacy of CBT-i in children and adolescents. We conducted a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO to select primary studies evaluating CBT-i in children and adolescents that were primarily diagnosed through standardized diagnostic criteria. The primary outcomes of the meta-analysis included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). Six randomized controlled trials and four open-label trials met all inclusion criteria. A total of 464 participants (ranging from 5-19 years of age) were included. Based on the results from sleep logs, a significant pooled effect size was observed for SOL and SE%. However, no significant pooled effect size was found for WASO or TST. Results from actigraphy were consistent with the sleep logs. A significant pooled effect size was observed for SOL and SE%, and no significant pooled effect size was found for WASO or TST. CBT-i might be effective in the treatment of children and adolescents with insomnia. PMID- 29791594 TI - Low-protein diet does not alter reproductive, biochemical, and hematological parameters in pregnant Wistar rats. AB - The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8) or a low protein (LP, 8% protein, n=14) diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05) in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein) between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation), mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05) at the end of pregnancy. Reproductive parameters (the dam offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates) were also not different (P>0.05) between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats. PMID- 29791595 TI - microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb. AB - Several microRNAs (miRNAs) have been reported as oncogenes or tumor suppressors in many cancers, including gastric cancer (GC). However, the role and molecular mechanism of miR-3129 in GC is largely unknown. We aimed to explore the function and the underlying molecular mechanism of miR-3129 in GC. Cancer tissues and corresponding adjacent tissues were collected from 50 patients with GC, and the expression of miR-3129 was detected by RT-qPCR. The expression of miR-3129 and pRb in human GC cell line SCG7091 was altered by transient transfection. Thereafter, MTT and flow cytometry assays were used to analyze cell viability and cell cycle. The expression of cyclin E, CDK2, CDK2 inhibitors (p16 and 21), and pRb were detected by RT-qPCR and western blot. A significant up-regulation of miR 3129 was observed in GC tissues compared to adjacent tissues. Overexpression of miR-3129 significantly improved cell viability after 4 days of post-transfection. Flow cytometry assay results showed that the miR-3129 overexpression arrested more SGC7901 cells at S phase. Moreover, overexpression of miR-3129 down regulated the expression of CDK2 inhibitors while it up-regulated the expression levels of cyclin E, CDK2, and pRb. Interestingly, we found that pRb inhibition reversed the effect of miR-3129 inhibitor on cell proliferation in SGC7901 cells, increased cell viability, reduced cells at G0/1 phase, and modulated the expression of proliferation-related factors. Our results revealed that miR-3129 functioned as an oncogene through positive regulation of pRb and may prove to be a promising option for molecular therapy of GC. PMID- 29791597 TI - Retraction notice for: Therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis. [Braz J Med Biol Res (2018) 51(2): e6812]. PMID- 29791596 TI - Treatment with Ilex paraguariensis (yerba mate) aqueous solution prevents hepatic redox imbalance, elevated triglycerides, and microsteatosis in overweight adult rats that were precociously weaned. AB - Early weaning (EW) leads to overweight, visceral obesity, hyperleptinemia, and insulin resistance in adulthood. Treatment with Ilex paraguariensis (yerba mate) improves obesity and insulin resistance in these animals. Here, we evaluated the effects of chronic treatment with yerba mate on the redox balance and liver morphology of overweight early-weaned rats. To induce EW, we wrapped the dams with bandages to interrupt milk access during the last 3 days of lactation. Control pups (C) had free access to maternal milk for the full 21 days of lactation. On postnatal day (PN) 150, EW offspring were subdivided into the EW+YM group, which received the aqueous extract of yerba mate (1 g/kg bw by gavage once a day for 30 days) and the EW group, which received water by gavage for the same period. All rats were euthanized on PN180. The EW group showed higher bound carbonyl (a marker of total protein oxidation), higher TBARS levels (a marker of lipid peroxidation), and lower superoxide dismutase (SOD) activity in liver tissue than the C group, as well as higher triglyceride content and microsteatosis. In plasma, the EW offspring showed higher TBARS levels. One month of yerba mate treatment normalized these parameters. Thus, we have shown evidence that yerba mate improved antioxidant defenses and mitigated liver dysfunction in overweight adult rats that were weaned prematurely. PMID- 29791598 TI - Chemical characterization, antioxidant and antimicrobial activity of propolis obtained from Melipona quadrifasciata quadrifasciata and Tetragonisca angustula stingless bees. AB - In this study, we investigated the chemical composition, and antioxidant and antibacterial properties of ethanolic extracts of propolis (EEP) from Melipona quadrifasciata quadrifasciata and Tetragonisca angustula. Chemical composition of EEP was determined by colorimetry and chromatographic (HPLC-DAD and UPLC-Q/TOF MS/MS) analysis. Antimicrobial activity of EEP was evaluated against gram positive (S. aureus, methicillin-resistant S. aureus, E. faecalis) and gram negative (E. coli and K. pneumoniae) bacteria by the minimal inhibitory concentration (MIC) test using the microdilution method. Furthermore, the growth curve and integrity of cell membrane of S. aureus and E. coli were investigated using standard microbiological methods. HPLC-DAD analysis showed that the EEP of M. quadrifasciata quadrifasciata has a more complex chemical composition than the EEP of T. angustula. Moreover, UPLC-MS analyses of M. quadrifasciata quadrifascita indicated flavonoids and terpenes as major constituents. The bactericidal activity of both EEPs was higher against gram-positive bacteria than for gram-negative bacteria. The EEP from M. quadrifasciata quadrifasciata presented MIC values lower than the EEP from T. angustula for all tested bacteria. The EEP from M. quadrifasciata quadrifasciata caused lysis of the bacterial wall and release of intracellular components from both E. coli and S. aureus. Our findings indicate that the chemical composition of propolis from stingless bees is complex and depends on the species. The extract from M. quadrifasciata quadrifascita was more effective against gram-positive than gram negative strains, especially against S. aureus and methicillin-resistant S. aureus compared to T. angustula extract, by a mechanism that involves disturbance of the bacterial cell membrane integrity. PMID- 29791599 TI - Ultra-short-term heart rate variability during resistance exercise in the elderly. AB - Despite the appeal of ultra-short-term heart rate variability (HRV) methods of analysis applied in the clinical and research settings, the number of studies that have investigated HRV by analyzing R-R interval (RRi) recordings shorter than 5 min is still limited. Moreover, ultra-short-term HRV analysis has not been extensively validated during exercise and, currently, no indications exist for its applicability during resistance exercise. The aim of the present study was to compare ultra-short-term HRV analysis with standard short-term HRV analysis during low-intensity, dynamic, lower limb resistance exercise in healthy elderly subjects. Heart rate (HR) and RRi signals were collected from 9 healthy elderly men during discontinuous incremental resistance exercise consisting of 4-min intervals at low intensities (10, 20, 30, and 35% of 1-repetition maximum). The original RRi signals were segmented into 1-, 2-, and 3-min sections. HRV was analyzed in the time domain (root mean square of the of differences between adjacent RRi, divided by the number of RRi, minus one [RMSSD]), RRi mean value and standard deviation [SDNN] (percentage of differences between adjacent NN intervals that are greater than 50 ms [pNN50]), and by non-linear analysis (short term RRi standard deviation [SD1] and long-term RRi standard deviation [SD2]). No significant difference was found at any exercise intensity between the results of ultra-short-term HRV analysis and the results of standard short-term HRV analysis. Furthermore, we observed excellent (0.70 to 0.89) to near-perfect (0.90 to 1.00) concordance between linear and non-linear parameters calculated over 1- and 2-min signal sections and parameters calculated over 3-min signal sections. Ultra-short-term HRV analysis appears to be a reliable surrogate of standard short-term HRV analysis during resistance exercise in healthy elderly subjects. PMID- 29791600 TI - Unilateral spatial neglect in the acute phase of ischemic stroke can predict long term disability and functional capacity. AB - OBJECTIVE: The aim of this study was to assess the relationship between the degree of unilateral spatial neglect during the acute phase of stroke and long term functional independence. METHODS: This was a prospective study of right ischemic stroke patients in which the independent variable was the degree of spatial neglect and the outcome that was measured was functional independence. The potential confounding factors included sex, age, stroke severity, topography of the lesion, risk factors, glycemia and the treatment received. Unilateral spatial neglect was measured using the line cancellation test, the star cancellation test and the line bisection test within 48 hours of the onset of symptoms. Functional independence was measured using the modified Rankin and Barthel scales at 90 days after discharge. The relationship between unilateral spatial neglect and functional independence was analyzed using multiple logistic regression that was corrected for confounding factors. RESULTS: We studied 60 patients with a median age of 68 (34-89) years, 52% of whom were male and 74% of whom were Caucasian. The risk for moderate to severe disability increased with increasing star cancellation test scores (OR=1.14 [1.03-1.26], p=0.01) corrected for the stroke severity, which was a confounding factor that had a statistically positive association with disability (OR=1.63 [1.13-2.65], p=0.01). The best chance of functional independence decreased with increasing star cancellation test scores (OR=0.86 [0.78-0.96], p=0.006) corrected for the stroke severity, which was a confounding factor that had a statistically negative association with independence (OR=0.66 [0.48-0.92], p=0.017). CONCLUSION: The severity of unilateral spatial neglect in acute stroke worsens the degree of long-term disability and functional independence. PMID- 29791602 TI - Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP): Achieving Better Agreement By Refining Diagnostic Criteria. PMID- 29791601 TI - Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users. AB - OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID- 29791603 TI - Evaluation Instruments for Quality of Life Related to Melasma: An Integrative Review. AB - The aim of this study was to analyze scientific production concerning the validation and cultural adaptation of quality of life evaluation instruments for patients with melasma and to offer a critical reflection on these methods. A literature review was performed based on a search of the Web of Science, Bireme, PubMed, Elsevier Scopus, and Google Scholar databases. All published articles from indexed periodicals in these electronic databases up to December 2015 were included. Eight articles were identified, of which only one (12.5%) referred to the development and validation of a specific instrument for evaluation of the quality of life of melasma patients. An additional six articles (75%) referred to transcultural adjustment and validation of the same instrument in other languages, and another (12.5%) article reported the development of a generic instrument for evaluation of quality of life in patients with pigment disorders. This review revealed only one specific instrument developed and validated in different cultures. Despite being widely used, this instrument did not follow the classic construction steps for psychometric instruments, which paves the way for future studies to develop novel instruments. PMID- 29791604 TI - Translation and cultural adaptation of the stroke impact scale 2.0 (SIS): a quality-of-life scale for stroke. AB - BACKGROUND: No specific quality-of-life scale for stroke patients has previously been translated and evaluated for reproducibility, for use in the Portuguese language. Internationally, the instrument for this purpose is the Stroke Impact Scale 2.0 (SIS). Use of of SIS enables comprehensive analysis on the impact of mild and moderate stroke on patients' lives. The aims here were to translate SIS into Portuguese, adapt it culturally, evaluate its reproducibility and correlate it with SF-36 among stroke patients. DESIGN AND SETTING: Translation and validation study. METHODS: The process of initial and retrograde translation was performed, in addition to cultural adaptation to the Brazilian language and culture. SIS was applied to 40 patients, who answered the questions three times. On the first day, the scale was applied twice by two independent researchers (to evaluate interobserver reproducibility). Fifteen days later, the scale was applied for a third time by another researcher (intraobserver reproducibility). The intraclass correlation coefficient (ICC) was used to measure the reproducibility of the SIS scale. RESULTS: The reproducibility of the whole scale was very good (ICC: 0.73 to 0.99). Intraobserver reproducibility in all domains was also very good (ICC: 0.85 to 0.95). Comparison of SIS with SF-36 showed that the domains of strength, mobility and activities of daily living (ADLs) correlated moderately with the functional capacity domain, as did the ADL domain with general health status. The other correlations were weak. The depression domain showed a moderate negative correlation with the memory and communication domains. CONCLUSION: The translation of the SIS 2.0 scale was easy to understand and it had good reproducibility among stroke patients. PMID- 29791606 TI - Evidence-based medicine. PMID- 29791605 TI - Athlete's heart in a Brazilian paralympic judo team. Case series study. AB - BACKGROUND: Athlete's heart is a term describing the cardiovascular effects of long-term conditioning among highly trained athletes. It is a variation of normal standards. DESIGN AND SETTING: Case series study at the cardiology division of a public university hospital. METHODS: We studied 14 visually handicapped paralympic athletes (8 men) in the national judo team. They were 26.3 +/- 6.4 years old, with body mass index 25 +/- 14, and had been practicing judo for 9.2 +/- 7.9 years. Clinical evaluations, electrocardiograms, exercise testing and echocardiograms were performed by independent observers. RESULTS: Signs of athlete's heart were found in all athletes, comprising left ventricular hypertrophy (5 cases), sinus bradycardia (5), T-wave juvenile pattern (3), T wave juvenile pattern (3), left atrial hypertrophy (2) and increased left ventricular volume (9 cases; 62.22 +/- 6.46 ml/m2). There were very strong correlations between left ventricular mass/body surface and endurance time (r: 0.91) and estimated peak oxygen uptake (r: 0.8). The correlations between left ventricular internal diastolic dimension and endurance time (r: 0.91) and estimated peak oxygen uptake (r: 0.8) were strong. Despite increased left ventricular dimensions (4 cases), atrial dimensions (1) and relative wall thickness (4), all athletes had normal left ventricular mass/body surface (89.98 +/- 21.93 g/m2). The exercise testing was normal: exercise duration 706 +/- 45 seconds and estimated peak oxygen uptake 62.70 +/- 9.99 mlO2/min. CONCLUSIONS: Signs of athlete's heart were seen frequently in the paralympic judo team. These demonstrated the presence of mild cardiac adaptations to training. PMID- 29791607 TI - Arteriosclerosis in Brazil. Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). PMID- 29791608 TI - HIV-1 genetic diversity and resistance to antiretroviral drugs among pregnant women in Ribeirao Preto (SP), Brazil. Cross-sectional study. AB - BACKGROUND: Increasing genetic diversity of HIV-1 and emergence of drug-resistant mutations may reduce the efficacy of antiretroviral therapy and prophylaxis that are used to prevent mother-to-child transmission. The aim of this study was to assess the genetic diversity and prevalence of drug-resistant mutations among HIV infected pregnant women. DESIGN AND SETTING: Cross-sectional study at an outpatient clinic for infectious diseases within gynecology and obstetrics. METHODS: This study evaluated the dynamics of HIV-1 subtypes and the prevalence of transmitted and acquired drug-resistant mutations among 38 HIV-infected pregnant women (20 previously exposed to antiretroviral therapy and 18 naive), in Ribeirao Preto (SP), Brazil, between 2010 and 2011. Genotyping was performed by means of molecular sequencing of the protease and reverse transcriptase regions of the HIV-1 pol gene. RESULTS: Subtype B was identified in 84.2% of the samples, recombinant forms between B and F in 7.9%, subtype F1 in 5.3% and the recombinant form K/F in 2.6%. No mutation associated with transmitted drug resistance was detected in the samples from the naive pregnant women, whereas mutations associated with acquired drug resistance were found in 35.0% of the pregnant women previously exposed to antiretroviral therapy. CONCLUSION: The results showed that subtype B predominated, while there was low prevalence of sequences with transmitted drug resistance. PMID- 29791609 TI - Association between multidrug resistance-1 C3435T gene polymorphism and right ventricular dysfunction in patients with chronic obstructive pulmonary disease: cross-sectional study. AB - BACKGROUND: Right ventricular (RV) dysfunction may develop over the course of chronic obstructive pulmonary disease (COPD) and is an important predictor of morbidity and mortality. Polymorphism of the multidrug resistance-1 (MDR-1) gene has been correlated with worse clinical findings among patients with COPD. Our aim here was to investigate the relationship between MDR-1 C3435T gene polymorphism and RV dysfunction in COPD patients. DESIGN AND SETTING: This was a cross-sectional study investigating the relationship between RV dysfunction and genetic defects in COPD patients. METHODS: Forty-one consecutive patients diagnosed with COPD and hospitalized due to acute exacerbation were enrolled. Polymorphism was analyzed using the strip assay technique. RV parameters were evaluated, and RV dysfunction was identified via transthoracic echocardiography. Patients were categorized into three groups according to gene polymorphism: MDR-1 CC (wild type, n = 9), MDR-1 CT (heterozygote mutant, n = 21) or MDR-1 TT (homozygote mutant, n = 11). RESULTS: The study included 14 males and 27 females (mean age 65 +/- 11 years). The mean systolic pulmonary artery pressure was 31.4 +/- 8 mmHg in the wild-type group, 42.2 +/- 12 mmHg in the heterozygote mutant group and 46.5+/-14 mmHg in the homozygote mutant group (P = 0.027). Presence of RV dilatation was significantly different among the three groups (33%, 71%, and 100%, respectively; P = 0.005). In multiple logistic regression analysis, MDR-1 C3435T gene polymorphism (OR = 9.000, P = 0.019) was an independent predictor of RV dysfunction after adjustment for potential confounders. CONCLUSION: MDR-1 C3435T gene polymorphism was associated with RV dysfunction in patients with COPD. PMID- 29791610 TI - What do Cochrane systematic reviews say about cardiac arrest management? AB - CONTEXT AND OBJECTIVE: Cardiac arrest is associated with high morbidity and mortality and imposes a significant burden on the healthcare system. Management of cardiac arrest patients is complex and involves approaches with multiple interventions. Here, we aimed to summarize the available evidence regarding the interventions used in cardiac arrest cases. DESIGN AND SETTING: Review of systematic reviews (SRs), conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo. METHODS: A systematic search was conducted to identify all Cochrane SRs that fulfilled the inclusion criteria. Titles and abstracts were screened by two authors. RESULTS: We included nine Cochrane SRs assessing compression techniques or devices (three SRs), defibrillation (two SRs) and other interventions (two SRs on hypothermia interventions, one on airway management and one on pharmacological intervention). The reviews included found qualities of evidence ranging from unknown to high, regarding the benefits of these interventions. CONCLUSION: This review included nine Cochrane systematic reviews that provided a diverse range of qualities of evidence (unknown to high) regarding interventions that are used in management of cardiac arrest. High-quality evidence was found by two systematic reviews as follows: (a) increased survival until hospital discharge with continuous compression, compared with interrupted chest compression, both administered by an untrained person and (b) no difference regarding the return of spontaneous circulation, comparing aminophylline and placebo, for bradyasystolic patients under cardiac arrest. Further studies are needed in order to reach solid conclusions. PMID- 29791611 TI - Effective scientific communication: reflections and tips. PMID- 29791612 TI - Application of a Brazilian test of expressive vocabulary in European Portuguese children. AB - Objective to investigate the performance of European Portuguese children in a Brazilian test of expressive vocabulary, seeking to identify differences between age groups and gender, and to verify its applicability in this population. Methods the sample consisted of 150 typical developed children, of both genders, between the ages of 5 and 6. All children attended public schools in the north area of Portugal. To assess the semantic performance, the expressive vocabulary sub-test of the language test (ABFW) was used, considering the percentage of usual verbal assignments and the classification (adequate/inadequate) according to the Brazilian reference values. Results the performance of the European Portuguese children indicated that at age 6 they have a higher percentage of correct answers in expressive vocabulary. As for the gender, there were only occasional differences: the girls showed a greater dominance in the semantic fields of clothing (both ages) and furniture and utensils (at age 5), whereas the boys showed more dominance in the semantic field means of transportation (6 years). Regarding classification, there was no difference between age groups in overall performance. Only the semantic field shapes and colors had more individuals of 6 years with inadequate performance. Conclusion the reference values adopted in the Brazilian population for semantic performance indicated that more than 80% of the children of each age group could have their performance classified as adequate. Such evidence suggests that this tool shows potential as an instrument of quantitative vocabulary's assessment of 5 and 6-years old children in European Portuguese. PMID- 29791613 TI - Speech-language pathology program for reading comprehension and orthography: effects on the spelling of dyslexic individuals. AB - Purpose Prepare a Speech-language Pathology Program for Reading Comprehension and Orthography and verify its effects on the reading comprehension and spelling of students with Developmental Dyslexia. Methods The study sample was composed of eleven individuals (eight males), diagnosed with Developmental Dyslexia, aged 09 11 years. All participants underwent a Speech-language Pathology Program in Reading Comprehension and Orthography comprising 16 individual weekly sessions. In each session, tasks of reading comprehension of texts and orthography were developed. At the beginning and end of the Program, the participants were submitted to a specific assessment (pre- and post-test). Results The individuals presented difficulty in reading comprehension, but the Cloze technique proved to be a useful remediation tool, and significant improvement in their performance was observed in the post-test evaluation. The dyslexic individuals showed poor performance for their educational level in the spelling assessment. At the end of the program, their performance evolved, but it remained below the expected, showing the same error pattern at the pre- and post-tests, with errors in both natural and arbitrary spelling. Conclusion The proposed Speech-language Pathology Program for Reading Comprehension and Orthography produced positive effects on the reading comprehension, spelling, and motivation to reading and writing of the participants. This study presents an unprecedented contribution by proposing joint stimulation of reading and writing by means of a program easy to apply and analyze in individuals with Developmental Dyslexia. PMID- 29791614 TI - Correlation between the Voice Handicap and Swallowing Quality of Life in patients with laryngeal cancer submitted to chemoradiotherapy. AB - Purpose To verify the correlation between the voice handicap and swallowing quality of life in individuals submitted to chemoradiotherapy for laryngeal cancer treatment. Methods Cross-sectional, observational and quantitative study. Fourteen male individuals diagnosed with laryngeal cancer were submitted to exclusive chemoradiotherapy treatment. The individuals completed the Voice Handicap Index (VHI) and the Swallowing Quality of Life (SWAL-QOL) questionnaires. Data were submitted to descriptive and inferential analysis using Spearman's Correlation Test to verify possible correlations among the scores of these instruments. Values of p <= 0.05 were considered statistically significant. Results No significant correlation was found between the total VHI and overall SWAL-QOL scores. However, there was significant correlation between the domain Functional of the VHI and the domains Fatigue and Social of the SWAL-QOL, between the domain Organic in the VHI and the SWAL-QOL domain Social, and total VHI score and SWAL-QOL domain Swallowing as a burden. Furthermore, chemoradiotherapy treatment had a greater impact on the voice than on the swallowing for the studied individuals. Conclusion The data showed a significant correlation between voice handicap and the impact of quality of life involving swallowing in individuals with laryngeal cancer submitted to chemoradiotherapy. This may affect individuals' emotional and social aspects, impacting their overall quality of life. PMID- 29791615 TI - Health literacy and self-rated health in adults primary care patients. AB - Purpose To verify the association between health literacy, social determinants and self-rated health in adult's primary health care patients. Methods this is an Observational cross-sectional study in which a total of 380 patients of the Unified Health System in the context of primary health care were interviewed. The sample was probabilistic, stratified by gender, age, and Basic Health Unit. Health literacy was evaluated by an instrument of analysis of the perception of adults about the understanding of health orientations and possible difficulties in this process (Health Literacy Scale). Descriptive and association analyses were performed (Pearson's chi-square test, p<=0.05). Results It was verified that the majority of the interviewees belongs to classes C1 and C2 and attended high school (complete or incomplete). Regarding self-rated health, to be considered healthy and with good health were the predominant perceptions. In the Health Literacy Scale, it was verified that most patients reported never presenting difficulties in the situations of this instrument, except understanding written orientations. It was observed the association with a statistical significance of the better perception of health literacy with higher educational level and economic classification, as well as with self-rated of good health. Conclusion There was a statistical association between health literacy, social determinants, and self-rated health in the analyzed adults. It is noteworthy the contribution of the Health Literacy Scale for emphasizing the perception of difficulties in everyday health situations. It is necessary to develop dialogic relationships that build more robust communication processes between professionals and healthcare patients to favor health literacy skills. PMID- 29791616 TI - Short- and long-latency auditory evoked potentials in individuals with vestibular dysfunction. AB - Purpose Evaluate the auditory pathway at the brainstem and cortical levels in individuals with peripheral vestibular dysfunction. Methods The study sample was composed 19 individuals aged 20-80 years that presented exam results suggestive of Peripheral Vestibular Disorder (PVD) or Vestibular Dysfunction (VD). Participants underwent evaluation of the auditory pathway through Brainstem Auditory Evoked Potentials (BAEP) (short latency) and P1, N1, P2, N2, and P300 cortical potentials (long latency). Results Nine individuals presented diagnosis of VD and 10 participants were diagnosed with PVD. The overall average of the long latency potentials of the participants was within the normal range, whereas an increased mean was observed in the short latency of waves III and V of the left ear, as well as in the I - III interpeak interval of both ears. Association of the auditory potentials with VD and PVD showed statistically significant correlation only in the III - V interpeak interval of the right ear for short latency. Comparison between the long and short latencies in the groups showed differences between VD and PVD, but without statistical significance. Conclusion No statistically significant correlation was observed between VD/PVD and the auditory evoked potentials; however, for the long latency potentials, individuals with VD presented higher latency in P1, N1, P2, and N2, where as participants with PVD showed higher latency in P300. In the short latency potentials, there was an increase in the absolute latencies in the VD group and in the interpeak intervals in the PVD group. PMID- 29791617 TI - Speech perception task with pseudowords. AB - Purpose Prepare a list of pseudowords in Brazilian Portuguese to assess the auditory discrimination ability of schoolchildren and investigate the internal consistency of test items and the effect of school grade on discrimination performance. Methods Study participants were 60 schoolchildren (60% female) enrolled in the 3rd (n=14), 4th (n=24) and 5th (n=22) grades of an elementary school in the city of Sao Paulo, Brazil, aged between eight years and two months and 11 years and eight months (99 to 136 months; mean=120.05; SD=10.26), with average school performance score of 7.21 (minimum 5.0; maximum 10; SD=1.23). Forty-eight minimal pairs of Brazilian Portuguese pseudowords distinguished by a single phoneme were prepared. The participants' responses (whether the elements of the pairs were the same or different) were noted and analyzed. The data were analyzed using the Cronbach's Alpha Coefficient, Spearman's Correlation Coefficient, and Bonferroni Post-hoc Test at significance level of 0.05. Results Internal consistency analysis indicated the deletion of 20 pairs. The 28 items with results showed good internal consistency (alpha=0.84). The maximum and minimum scores of correct discrimination responses were 34 and 16, respectively (mean=30.79; SD=3.68). No correlation was observed between age, school performance, and discrimination performance, and no difference between school grades was found. Conclusion Most of the items proposed for assessing the auditory discrimination of speech sounds showed good internal consistency in relation to the task. Age and school grade did not improve the auditory discrimination of speech sounds. PMID- 29791618 TI - Performance of children with speech sound disorders in the dynamic evaluation of motor speech skills. AB - Purpose To compare performance between children with typical speech acquisition, phonological disorders, and childhood apraxia of speech for the variables overall articulatory accuracy and consistency of the Dynamic Evaluation of Motor Speech Skill - Brazilian Portuguese version (DEMSS-BR). Methods Study participants were 18 children of both genders aged 4 years and 6 months to 5 years and 8 months. The sample was divided into three groups: six children with typical speech acquisition (TSA), six children with phonological disorder (PD), and six individuals with childhood apraxia of speech (CAS). All participants were submitted to the DEMSS-BR and had their subscores of speech accuracy and consistency measured. Performance comparison between the groups was statistically evaluated using the Mann-Whitney U Test. Results Participants in the group with CAS presented poorer performance for the variables overall articulatory accuracy and consistency compared with those of participants in the other two groups. Conclusion The group of children with childhood apraxia of speech presented poorer performance on the DEMSS-BR compared with those of the groups with typical speech acquisition and phonological disorders. The study demonstrated that the DEMSS-BR assists with differential diagnosis of children with speech sound disorders. PMID- 29791619 TI - Temporal ordering and reading competence of words and pseudowords: a preliminary study. AB - Purpose Analyze the association of simple and complex auditory temporal ordering skills with reading competence tasks in students. Methods Pilot phase of a cross sectional study conducted with a non-probabilistic sample of 22 schoolchildren aged eight to ten years. Instruments for evaluation of reading competence tasks and simple and complex auditory temporal ordering abilities were used. Results Most participants obtained adequate results in the tests of simple auditory temporal ordering (SATO) and reading competence (RC), but inadequate results in the test of complex auditory temporal ordering (CATO). The association of reading competence with temporal processing showed no statistical significance. Conclusion The study evidenced the importance to conduct more robust studies on the theme and the viability of data collection in the school scenario. PMID- 29791620 TI - Intervention time until discharge for newborns on transition from gavage to exclusive oral feeding. AB - Purpose Measure the intervention time required for transition from gavage to exclusive oral feeding, comparing newborns exposed exclusively to the mother's breast with those who, in addition to breastfeeding, received supplementation using a cup or baby bottle. Methods Analytical, longitudinal, cohort study conducted with 165 newborns (NB) divided into groups according to severity of medical complications (G1-with no complications; G2-with significant complications), and into subgroups according to feeding mechanism (A and B). All NBs were low birth weight, on Kangaroo Mother Care, and breast stimulated according to medical prescription and hospital routine. Regarding feeding pattern, subgroup A comprised NBs exclusively breastfed at hospital discharge, whereas subgroup B was composed of NBs fed through cup/bottle at some time during hospitalization. The number of days spent in each stage of transition was recorded for each NB. Results History of clinical complications significantly influenced total intervention time. Study participants in subgroups G1-A (10 days), G1-B (9 days), and G2-A (12 days) displayed greater chances of early discharge compared with those in subgroup G2-B (16 days). Conclusion NBs with no important history of clinical complications displayed greater chances of early hospital discharge. NBs with significant history of clinical complications that underwent gavage to exclusive breastfeeding transition presented smaller intervention time than those that required supplementation using cup/bottle. Feeding transition using the gavage-to-exclusive oral feeding technique is recommended for Speech-language Pathology practice in Neonatology. PMID- 29791621 TI - Speech-language pathology aspects in a pediatric case of head and neck arthrogryposis. AB - Arthrogryposis is a rare, multiple, congenital syndrome of non-progressive nature characterized by a series of genetic malformations, as well as stiffness and joint contractures. This is a clinical case study whose objective is to describe speech-language pathology disorders through the evaluation process in a case of arthrogryposis in Pediatrics. The medical records of a patient were analyzed from birth. A complete clinical evaluation of pediatric dysphagia was performed, establishing a diagnosis of severe oropharyngeal dysphagia evidenced by functional and structural impairments. Hearing loss was detected in association with this condition. PMID- 29791622 TI - Profile of the body mass index and associated factors in active elderlies. AB - OBJECTIVE: Identifying the profile of Body Mass Index and associated factors in active elderlies. METHOD: This is an analytical type of research with cross sectional design and quantitative approach, with sample represented by 105 elderly people. The research instrument consisted of Cognitive assessment, Sociodemographic data, Health conditions and Motor performance evaluation. The data were analyzed by using descriptive analysis and binary logistic regression. RESULTS: The elderlies without partners have 7.753 times the chance of presenting excess weight when compared to those with partners. Having an income higher than a minimum wage represents 6.014 times the chance of being overweight. Not having health problems amounts to 0.015 times the chance of being overweight. In the motorperformance, not presenting limitation of balance represents 6.785 times the possibility of being affected by excess weight. PMID- 29791623 TI - Social representation of elderly people on falls: structural analysis and in the light of Neuman. AB - OBJECTIVE: To understand the symbolic elements and the hierarchical system of representations of elderly people on falls, according to Abric's structural analysis and Neuman's theory. METHOD: Abric structural approach developed at the home of primary care users in a city of Minas Gerais. A free evocation technique of images triggered by images was performed in 2016 with elderly individuals (>=65 years old). Data treated by dictionary of equivalent terms; processed in Evoc 2000 software converging, analytically, according to Neuman. Ethical/legal criteria were met. RESULTS: 195 people participated, 78.5% were women, and 45.1% were aged >=75 years. Summarized 897 words; 155 different ones. Central nucleus containing cognates: dizziness-vertigo-labyrinthitis and slipper-shoes (behavioral and objective dimension). The word disease integrated the area of contrast. Environmental and personal stressors were identified according to Neuman. Final considerations: Objects and risk behaviors for falls integrated the representations, although environmental and personal stressors indicate the need for preventive interventions in the environment and in the intrapersonal dimension. PMID- 29791624 TI - The meaning of religion/religiosity for the elderly. AB - OBJECTIVE: To understand the meaning of religion/religiosity for the elderly. METHOD: A qualitative, phenomenological study, based on Martin Heidegger. Thirteen older women registered in an Urban Social Center of Salvador, Bahia, Brazil aged between 60 and 84 years participated in the study. The collection of testimonies was carried out from November 2013 to May 2014 through phenomenological interviews. RESULTS: Hermeneutics has unveiled the unit of meaning: Meanings of religion/religiosity in the daily life of the elderly. Religion/religiosity offers comfort and well-being to the elderly person, helping to overcome changes arising from the aging process. Final considerations: The nurse, while providing care, should expand his/her vision in relation to the subjectivity of the elderly, in order to understand that religion/religiosity gives meaning to their existence. PMID- 29791625 TI - Self-care of elderly people after the diagnosis of acquired immunodeficiency syndrome. AB - OBJECTIVE: to characterize the seropositive elderly for the Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome (HIV/AIDS) in their socio-demographic aspects; to understand how the elderly take care of themselves from the diagnosis of HIV/AIDS. METHOD: Qualitative, descriptive, exploratory research conducted at a Voluntary Counseling and Testing Center with 10 elderly people receiving treatment for HIV/AIDS. The data were analyzed according to the content analysis. RESULTS: Data show the elderly people's lack of knowledge about HIV/AIDS transmission, the experience of being elderly and having HIV/AIDS, caring for oneself and life after diagnosis of HIV/AIDS in their daily lives. Final considerations: The diagnosis of HIV/AIDS seropositivity in the elderly generates a blend of feelings and fears that lead to food changes, adherence to treatment and the renunciation of daily and social habits, manifested as ways of self-care. PMID- 29791626 TI - Aging and quality of life of elderly people in rural areas. AB - OBJECTIVE: To evaluate the quality of life and health of elderly in rural areas of Minas Gerais State's center-west. METHOD: Cross-sectional study, in four municipalities of Minas Gerais State, by interviewing elderly people. Associations between socio-demographic and quality of life variables were tested, separated into "satisfactory"/"unsatisfactory" with values from the median of positive answers. It was used the chi-square test, Fisher's test and regression. RESULTS: 182 elderly answered the questions and showed a relation with the "satisfactory" quality of life - bivariate (p < 0.05): age by 69 years (61.6%), married (61.7%), living by 54 years in rural areas (68%), with no financial support (59.5%), living with someone else (61%), non-smoker (60%), presenting good health (76.7%), satisfied with life (69.6%); regression: not having financial support, living with someone else and not smoking. CONCLUSION: Elderly people in rural areas present good quality of life/health in the cognitive aspect, access to services, goods, habits, but awareness must be constant due to their weakness. PMID- 29791627 TI - Emergency care units and dimensions of accessibility to health care for the elderly. AB - OBJECTIVE: to understand the conception of the elderly and their caregivers about the accessibility to health mediated by the service in Emergency Care Units. Methodo: a qualitative study conducted with 25 elderly patients and caregivers at Emergency Care Units in a city of Parana, using Grounded Theory as a methodological reference. RESULTS: According to the participants, the resources available in these services guarantee medical consultation and provide access to exams and medicines. Such resources have attracted patients and caused excess demand, which implies a set of compromising factors for the quality of care in these services. Final considerations: Investments in the restructuring of the care network, especially in primary care, with an increase in the number of consultations and the creation of a bond, can contribute to the emergency care units achieving the goal of access to qualified assistance to the elderly population. PMID- 29791628 TI - Validation of the Falls Efficacy Scale - International in a sample of Portuguese elderly. AB - OBJECTIVE: to translate and adapt Falls Efficacy Scale - International (FES-I). To analyze the psychometric properties of the FES-I Portugal version. METHOD: psychometric study. Sample consisting of 170 elderly people residing in the Autonomous Region of Madeira. A two- part form was used (sociodemographic characterization and FES-I Portugal). The cross-cultural adaptation was performed and the following psychometric properties were evaluated: validity (construct, predictive, and discriminant), reliability (Cronbach's alpha), and inter-rater reliability. RESULTS: the results allow us to verify a dimension of less demanding physical activities and another of more demanding physical activities. The inter-rater reliability study was 0.62, with an interclass correlation coefficient of 0.859, for a 95% confidence interval. The internal consistency of the Portuguese version was 0.962. CONCLUSION: the validity and reliability of the FES-I Portugal are consistent with the original version and proved to be appropriate instruments for evaluating the "impaired walking" and "risk of falls" nursing diagnoses in the older people. PMID- 29791629 TI - Self-perceived health and clinical-functional vulnerability of the elderly in Belo Horizonte/Minas Gerais. AB - OBJECTIVE: To determine the self-perceived health status and clinical-functional vulnerability of the elderly attended at a Reference Center of Minas Gerais, Brazil and to evaluate the association between these variables through the Clinical-Functional Vulnerability Index (IVCF-20) instrument. METHOD: This is an epidemiological, retrospective study of 311 medical records. Statistical analyses were performed using the Stata program; the evaluations were by Pearson's Chi square test and Poisson regression models. RESULTS: The majority of the elderly presented negative self-perceived health status(70.10%); there was statistical significance between negative self-perceived health and the variables of mood and recent hospitalization. CONCLUSION: Perceived health status influences the morbidity and mortality of the elderly. Mood disorders and recent hospitalizations directly interfere with active aging. PMID- 29791630 TI - Violence against the Brazilian elderlies: an analysis of hospitalizations. AB - OBJECTIVE: to identify the prevalence of physical aggression and neglect and abandonment in the hospitalizations of Brazilian elderly people for violence and assault from 2008 to 2013 and the association of these causes with socio demographic variables related to hospitalization. METHOD: quantitative, descriptive, cross-sectional study with elderlies hospitalized for assault. INCLUSION CRITERIA: to be 60 years old or over, to have been hospitalized in the Unified Health System (SUS) for assault or neglect and abandonment, between 2008 and 2013. The data were collected in February 2016, in Datasus database and descriptive and inferentially, using the Chi-square distribution, in the Epi Info 3.5.4 program. RESULTS: the prevalence of hospitalizations due to assaults and violence prevailed among 60 and 69 years old men in the public sector. For abandonment and neglect, there was a higher prevalence in women, over 80 years old, in the public sector. CONCLUSION: nurses must be able to identify and prevent violence against the elderly. PMID- 29791631 TI - Educational technology: a facilitating instrument for the elderly care. AB - OBJECTIVE: To develop educational technology with caregivers of older people based on the needs, difficulties and concerns related to the elderly care expressed by the caregivers themselves. METHOD: Research of qualitative nature, with participant observation, based on concepts used by Paulo Freire. Data collection and analysis used the "World Cafe" methodology and the thematic content analysis, respectively. RESULT: The needs of these caregivers refer to their training and information on aging. The difficulties highlighted are deterrents to quality assistance to older adults, such as: insufficient resources, environmental factor and relationship with the family. The interests are evident in relation to the care and to its more subjective relationship. Final considerations: Educational technologies, printed matter and media, developed along with the caregivers, contribute to orientation and information of caregiver, population and professionals as facilitating instruments, regarding elderly care. PMID- 29791632 TI - Population aging and the Nursing commitment. PMID- 29791633 TI - Elderly and caregiver demand: proposal for a care need classification. AB - OBJECTIVE: To propose a care need classification for elderly people by identifying their functional demands. METHOD: Cross-sectional study carried out in Sao Paulo, in 2006, with 1,413 elderly (>= 60 years old), participants in the Health, Well-being and Aging study (SABE - Saude, Bem Estar e Envelhecimento). For the care need classification, we used the Guttman Scaling method e the frequency of assistance required by the elderly. RESULTS: The hierarchy of activities of daily living had good internal consistency (alpha = 0.92) and satisfactory coefficients of reproducibility (98%), scalability (84%) and minimum marginal reproducibility (87%). Care need was categorized into: no need (requires no caregiver), minimum need (requires caregiver sporadically), moderate need (requires caregiver intermittently) and maximum need (requires full-time caregiver). CONCLUSION: This classification will allow identifying elderly that need assistance in everyday activities and will orientante health professionals in the development of a line of care. PMID- 29791634 TI - Effects of health education in the elderly with mild cognitive impairment. AB - OBJECTIVE: to analyze the effects of health education on both cognition and depressive/anxiety symptoms in the elderly with Mild Cognitive Impairment (MCI). METHOD: this is a randomized and controlled clinical trial. Participants (n=22) were recruited from a specialized outpatient clinic, and assigned into two groups: a Health Education Group (HEG) (n=10) and a Control Group (CG) (n=12). The participants were evaluated before and after the intervention, which was composed of classes and dynamics. The intervention consisted of 20 meetings, over a period of five months. The assessment was performed by means of the Addenbrooke's Cognitive Examination - Revised (ACER), the Mini-Mental State Examination to access participant's cognitive state, and the Beck's Scale to access depressive/anxiety symptoms. A Memory Complaints Scale (EQM) was also used. The analysis was carried out using the Student's t test for paired samples. RESULTS: the HEG group demonstrated an improvement in attention/orientation (p= 0,026), memory (p=0.001), language (p= 0.033), and ACE-R (p= 0.003). On the other hand, the CG did not present improvement. CONCLUSION: the results highlight the importance of non-pharmacological interventions in older adults with MCI to reduce cognitive deficits. PMID- 29791635 TI - Elderly people with mental disorders: experiencing the use of psychotropic medicines. AB - OBJECTIVE: To interpret the experience of the elderly with mental disorder in the use of psychotropic medicines. METHOD: Qualitative study in the interpretative modality, supported by the Grounded Theory. It was carried out from interviews with 16 elderly people with mental disorder and six relatives, totaling 22 participants. RESULTS: In the experience of the use of psychotropic medicines, the elderly with mental disorders become aware of their condition, attribute meaning and establish strategies for the correct use. On the other hand, they express their dissatisfaction with being dependent on psychotropic medicines to live without symptoms, face their side effects and do not always use them correctly. CONCLUSION: The use of psychotropic medicines is a priority in the life of the elderly and, in view of the fragilities found, it is necessary a continuous monitoring of health professionals. PMID- 29791636 TI - Family health strategy: relevance to the functional capacity of older people. AB - OBJECTIVE: to identify the functional capacity of older people based on their performance on basic activities of daily living. METHOD: a cross-sectional study, carried out through the record of the Family Health teams working in the urban area of a city in northern Minas Gerais, in 2015. To assess the functional capacity of 373 older people, the Katz Scale was applied, which includes dimensions on the performance of daily living activities. The interviews took place in the participants' households. RESULTS: of the total participants, 6.9% had some degree of dependence. Those aged over 80 years old and were living without a partner had about three times more chances of presenting higher levels of functional dependence. CONCLUSION: most older people enrolled in a Family Health Strategy had their functional capacity preserved. PMID- 29791637 TI - Board games: gerotechnology in nursing care practice. AB - OBJECTIVE: To create a board game as a form of gerotechnology to promote active and healthy aging. METHOD: This was a qualitative, convergent care study conducted with 32 older adults. Individual interviews, creativity and sensitivity techniques, group discussions, and participant observations guided by Paulo Freire's theoretical framework of problematization were used to produce data. The participants and researchers assessed the entire production process at the end of the study, after the gerotechnology was implemented in the groups. French discourse analysis was adopted. RESULTS: Patented under registration no. BR 1020160107725, the game was created as a technological product based on the discussions with older adults, considering the conceptions, knowledge and practices shared by them about aging. Final considerations: The gerotechnology implemented in clinical nursing practices functioned as a playful resource to exercise self-determination and independence among older adults, boosting memory, self-esteem, socialization processes, exchanging experiences and shared learning. PMID- 29791638 TI - Assessment of ulceration risk in diabetic individuals. AB - OBJECTIVE: To identify the risk factors for foot ulceration through the tracing of diabetic peripheral neuropathy and peripheral arterial disease in individuals with type I and II diabetes, who were assisted in reference centers of the Federal District, Brazil. METHOD: a cross-sectional and analytical study, with the assessment of 117 individuals in outpatient clinics of the Federal District. Continuous variables were compared through Mann-Whitney test, and categorized variables, through Chi-square test for univariate analysis and Logistics regression test for multivariate analysis. RESULTS: painful diabetic peripheral neuropathy was present in 37 (75.5%) of the individuals with neuropathy. Deformities and loss of protective plant sensibility were related to neuropathy (p=0.014 and p=0.001, respectively). Of the 40 (34.2%) individuals in the sample who presented peripheral arterial disease, 26 (65%) presented calcification risk. CONCLUSION: signs of painful peripheral polyneuropathy, peripheral arterial disease, deformities, loss of protective plantar sensibility, and dry skin were identified as risk factors for ulceration. PMID- 29791639 TI - Validity and reliability of the Brazilian version of the Caregiver Reaction Assessment. AB - OBJECTIVE: To analyze the validity based on the internal structure and reliability of the Brazilian version of the Caregiver Reaction Assessment (CRA) applied to informal caregivers of dependent elderly. METHOD: A methodological study with 120 informal caregivers of the elderly. Validity based on the internal structure evaluated by exploratory factorial analysis, with extraction of main factorial axes, varimax orthogonal rotation and retention of factors by parallel analysis. Reliability assessed by Cronbach's alpha. RESULTS: The instrument revealed a factorial structure different from the original version: three factors were identified, equivalent to subscales, self-esteem, daily activities and family support, with explained variance of 42%. The values of the Cronbach alpha for the items belonging to each subscale were, respectively: 0.71, 0.81 and 0.83. CONCLUSION: The Brazilian version of CRA presents good evidence of validity based on internal structure and is reliable, and can be used to assess the overload of informal caregivers of dependent elderly. PMID- 29791640 TI - Factors associated to the dependence of older adults with diabetes mellitus type 2. AB - OBJECTIVE: to identify factors associated to the dependence of older adults with Diabetes Mellitus, Type 2 Method: analytical and epidemiological study with 99 older adults. The Brazilian Multidimensional Functional Assessment Questionnaire and a questionnaire composed by socio-demographic and clinical variables were used. The independent variables were described and compared to the level of dependence obtained by the chi-square test or the Fisher test, the strength of association was estimated by Odds Ratio and multiple regression. RESULTS: the level of dependence prevailed in 79.8% of the sample. Higher chances of dependence were associated to: cutting toenails; performing household chores; presenting geriatric problems; urinary incontinence; time of diagnosis of diabetes; falls in the past year; and physical inactivity. CONCLUSION: considering the positive association of diabetes mellitus to the increased chance of dependence among older adults, there is need for direction and adoption of effective measures to ensure the functionality and quality of life of older adults with diabetes mellitus in a fair and democratic way. PMID- 29791641 TI - Suicidal ideation and attempt of older women in Northeastern Brazil. AB - OBJECTIVE: to associate the life experiences of older women from the Northeast of Brazil with their suicidal ideation and attempts. METHOD: Qualitative study with fourteen older adults from Piripiri (PI), Teresina (PI), Fortaleza (CE) and Recife (PE) who were interviewed between November 2013 and July 2014. The organization of data originated the themes: experiences of abuse throughout their lives; marital fractures and social isolation; weakened motherhood. RESULTS: The women were born and lived most of their life in the countryside, amid poverty and social exclusion. They had a history of abuse, physical and sexual violence, perpetrated by intimate partners and/or family members. They experienced social isolation, weakened emotional bonds and several suicide attempts. Final considerations: The life of these older women was affected by traumatic events that enhanced feelings of hopelessness, depressive symptoms and the absence of a plan for the future, making them consider suicide as a way to anticipate death. PMID- 29791642 TI - Integrative review of literature: nursing care to aged people with HIV. AB - OBJECTIVE: To identify evidences in scientific Brazilian literature on nursing care to aged people with HIV. METHOD: Integrative review of literature from databases: Latin American and Caribbean Literature on Health Sciences (LILACS), Scientific Eletronic Library Online (SciELO), Cochrane and the Nursing Database (BDENF). The applied inclusion criteria were publications that were fully available from 2001 to 2015 and answered to the guiding question of this study. RESULTS: We included 13 studies; and the categories that allowed a better presentation of the scientific evidence on nursing care to aged people with HIV carrier were: Epidemiological profile, perceptions and experiences of aged people with HIV and nursing care to aged people with HIV. CONCLUSION: The studies address nursing care from a clinic that follows NANDA diagnoses of strong individualizing approach and low consideration of social aspects. PMID- 29791643 TI - Conversation map: an educational strategy in the care of elderly people with diabetes mellitus. AB - OBJECTIVE: To report the experience of using diabetes conversation maps as an educational strategy for diabetic elderly people. METHOD: Experience report, conducted from July to December 2016 in a specialized outpatient clinic for diabetics, in Fortaleza, Ceara, Brazil. A total of 72 users participated, between diabetics and those accompanying them. RESULTS: The participants talked about issues that were not addressed in personal consultations, and could see themselves through the stories of others, thus realizing they were not alone and that others also experienced the same difficulties as them. Through empathy and the accounts of others, participants built knowledge and practices for their own daily lives. Final Considerations: The conversation map enables professionals to empower patients with diabetes, promoting self-care and ensuring better control over the disease, in order to prevent or delay the onset of related complications. PMID- 29791644 TI - Temporal analysis of the functional status of older people in the state of Paraiba, Brazil. AB - OBJECTIVE: To verify the profile and the functional status of older people living in the state of Paraiba, Brazil, from a temporal perspective. METHOD: This was a descriptive study with secondary analysis of data from the Health Indicator and Aging Policy Monitoring system (SISAP-Idoso - Sistema de Indicadores de Saude e Acompanhamento de Politicas do Idoso) between 2000 and 2010. RESULTS: Over the analyzed period, there was a growth of older women, people older than 85 years, residents of urban areas, older people who live alone and who are not responsible for the household. There was also a decrease of illiterate older people, with monthly income of up to one minimum wage and in poverty situations. Concerning the functional status, the proportion of older people who reported any permanent mental, motor, visual or hearing disabilities has increased. CONCLUSION: We suggest that the assistance must be directed towards environmental variables that can influence the functional state, such as illiteracy, low income and disabilities that contribute to the weakening of older people and must be overcome. PMID- 29791645 TI - Gerontological contributions to the care of elderly people in long-term care facilities. AB - OBJECTIVE: To analyze Brazilian scientific productions from the last 11 years which show the contributions of nursing to elderly people in long-term care facilities. METHOD: This is an integrative literature review. The search took place in the Virtual Health Library (VHL) in the BDENF and LILACS databases and the SCIELO virtual library, between June and October 2016, using the keyword long term care facility and the descriptors nursing and geriatrics. RESULTS: Eleven studies were selected, published 2005 and 2016, with various methodological approaches that enabled discussion of the proposed objective. CONCLUSION: The contributions of nursing to institutionalized elderly people were linked to health promotion measures, as well as simple interventions, such as listening, interacting, offering recreation and helping in psychoaffective relationships. These activities contributed to raising the self-esteem of the individuals. PMID- 29791646 TI - Repercussions of hospitalization due to fall of the elderly: health care and prevention. AB - OBJECTIVE: To know the repercussions of the fall reported by the elderly and their caregiver during hospitalization in a public hospital in Florianopolis city from October to December 2014. METHOD: Exploratory research with a qualitative approach, conducted by depth interviews with 16 participants, the eight elderly were hospitalized for falls and eight elderly caregivers. Data analysis were performed through the Thematic Content Analysis. RESULTS: It was evidenced the thematic axis: Faller Elderly supported by four thematic categories: Changes caused by Falls, I am a faller, I take care of me and Prevention of the Fall. The repercussions of the fall were evidenced in the impairment of the health condition, self-care and functional capacity. We observed the naturalization of the phenomenon and the passivity with the harmful consequences of the event. Final Considerations: The fall is valued the more negative its repercussion, such as the need for hospitalization and surgery. Managing the vulnerability of the elderly, especially in primary care, evaluating their comorbidities and their internal and external environment, will minimize unfavorable consequences and the social and financial cost of hospitalizations. PMID- 29791647 TI - Active methodologies for graduation in nursing: focus on the health care of older adults. AB - OBJECTIVE: To describe the experience of the use of simulation as active teaching methodology in the Developmental Psychology discipline and share its impacts on the students' learning process. METHOD: Based on Active Methodologies, the students in Nursing of Universidade do Oeste Paulista - Presidente Prudente-SP developed simulated visits to older users of the Family Health Strategies. RESULTS: In accordance with the 2014 National Curriculum Guidelines and the Brazilian Unified Health System, particularities of the needs of older adults at their homes were problematized. Final considerations: Addressing the biopsychosocial needs and integrality associated with the health of older adults in simulated home visits provides a differentiated instrument in the development of skills and competence of future nurses. PMID- 29791648 TI - Time use by family caregivers of elderly with dementia: an integrative review. AB - OBJECTIVE: To describe the development of measures used between 1993 and 2016 to evaluate time use by family caregivers of elderly with dementia and to find out the patterns of time use identified in the literature. METHOD: An integrative review of articles was performed, indexed by the following terms: time use management, family caregiver and elderly. RESULTS: A total of 17 articles were found, of which seven were methodological. Among these seven articles, five were psychometric. The most frequently used measures were self-reporting (matrices, questionnaires and inventories), validated through objective measures of occurrence and duration. Longitudinal, prospective, clinical and correlational studies showed that care time covaries with the receptors' dependence and that the caregivers' subjective well-being is more affected by the time restriction to free choice activities than the burden resulting from obligatory activities. Final considerations: Valid self-reporting measures are widely used nowadays and they are considered to be effective to assess the objective and subjective costs of health care for dementia. PMID- 29791649 TI - Bouts of exercise elicit discordant testosterone: cortisol ratios in runners and non-runners. AB - OBJECTIVE: The testosterone:cortisol ratio (T:C) is suggested to be used in order to examine whether physical exercise generates either a "catabolic environment" or an "anabolic environment". The present study aims to evaluate the acute time course profile of cortisol and testosterone due to an episode of physical exercise. A biphasic profile in the T:C ratio response was hypothesized. MATERIALS AND METHODS: Morning sessions of treadmill running at two different intensities (Heart Rate at 65% and 80% of the maximum cardiac reserve) were performed by 6 male non-runners (NR) and 12 trained male runners (subdivided into trained runners T1 and T2). Cortisol and testosterone were measured in saliva. NR and T1 ran for 30 minutes at both intensities, and T2 ran for 46 minutes (+/- 4.1) at 65% and 42 minutes (+/- 3.5) at 80%. RESULTS: In the 80% heart rate target, both groups of runners showed the biphasic time-profile, while the non runners group did not. However, at the 65% level, none of the groups presented the hypothesized biphasic response. CONCLUSIONS: A biphasic time-profile in the testosterone:cortisol ratio can be seen in short-bout, high intensity exercise (treadmill running) during the morning in men trained for this specific physical activity. PMID- 29791650 TI - Metabolic syndrome components are associated with oxidative stress in overweight and obese patients. AB - OBJECTIVE: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. SUBJECTS AND METHODS: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI >= 30 kg/m2. RESULTS: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). CONCLUSIONS: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects. PMID- 29791652 TI - Inflammatory myopathy in the context of an unusual overlapping laminopathy. AB - Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Kobberling-like); mild hypertrophic cardiomyopathy, with Wolff-Parkinson- White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant. PMID- 29791653 TI - Waist circumference is an effect modifier of the association between bone mineral density and glucose metabolism. AB - OBJECTIVE: The role of bone markers on insulin resistance (IR) remains controversial. The objective of this study is to evaluate the association between bone mineral density (BMD) and glucose metabolism and investigate if visceral hyperadiposity, evaluated by waist circumference (WC), is an effect modifier of this association. SUBJECTS AND METHODS: Cross-sectional analysis with 468 young adults from the fourth follow-up of the 1978/79 Ribeirao Preto prospective birth cohort, Brazil. BMD, total osteocalcin (OC), fasting plasma glucose and insulin concentrations were assessed. IR, sensitivity (S) and secretion (beta) were estimated by homeostasis model assessment (HOMA) indexes. Multiple linear regression models were constructed to estimate the association between BMD and glucose metabolism. Beta coefficient, R2 and p-values were provided. WC was tested as an effect modifier and OC as a confounder. The covariates were selected based on Direct Acyclic Graph. RESULTS: Significant interaction between BMD (femoral neck and proximal femur areas) and WC on glucose metabolism was observed in the adjusted models. Subjects with increased WC presented a positive association between BMD and log HOMA1-IR while an inverse association was found in those with normal WC (femoral neck R2 = 0.17, p = 0.036; proximal femur R2 = 0.16, p = 0.086). BMD was negatively associated with log HOMA2-S in individuals with increased WC and positively in those with normal WC (femoral neck R2 = 0.16, p = 0.042; proximal femur R2 = 0.15, p = 0.097). No significant associations between BMD, log HOMA2-beta and OC and glucose metabolism markers were observed. CONCLUSIONS: BMD was associated with glucose metabolism, independently of OC, and WC modifies this association. PMID- 29791651 TI - Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy. AB - OBJECTIVES: Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. SUBJECTS AND METHODS: Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). RESULTS: Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. CONCLUSIONS: It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice. PMID- 29791654 TI - Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study. AB - OBJECTIVE: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. SUBJECTS AND METHODS: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. RESULTS: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). CONCLUSIONS: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency. PMID- 29791655 TI - Accuracy of sentinel lymph node mapping in detecting occult neck metastasis in papillary thyroid carcinoma. AB - OBJECTIVES: The objectives of this study were to evaluate the following: 1) the accuracy of sentinel lymph node mapping (SLNM) in detecting metastasis in papillary thyroid carcinoma (PTC), and 2) if SLNM could modify the American Joint Committee on Cancer (AJCC) staging of previous cN0 PTC patients. SUBJECTS AND METHODS: Forty SLNM were performed prospectively in 38 consecutive cN0 PTC patients, with total thyroidectomy and elective compartment neck dissection (CND). The results of SLNM were compared with CND pathological findings to verify the accuracy of sentinel SLNM. RESULTS: The mean patients' follow-up was 36 months. A total of 133 SLN were found at levels VI, II, III and IV. The SLN was identified in 95% of the patients with one false negative, 95% sensitivity, a 94% negative predictive value and 97% accuracy. The SLNM upstaging from cN0 to pN+ was 49%, and to stages III and IVa, it was 21%. CONCLUSIONS: For this series of cN0 PTC patients: 1) SLNM accuracy was 97%, and 2) SLNM upstaging from cN0 to pN+ was 49%, whereas to stages III and IVa, it was 21%. PMID- 29791656 TI - Long term maintenance of glucose and lipid concentrations after Roux-en-Y gastric bypass. AB - OBJECTIVE: Roux-en-Y gastric bypass (RYGB) reduces body weight and the comorbidities associated with obesity. The aim of this study was to evaluate whether glucose and lipid profiles were maintained during a 5-year follow-up period after RYGB. SUBJECTS AND METHODS: Anthropometric and laboratory data from 323 patients who had undergone this operation were analyzed. Differences in laboratory variables between the baseline and 12, 24, 36, 48 and 60 months postoperatively (PO) were assessed using a one-way ANOVA test to compare the three groups. Delta significance using one-way ANOVA was performed to assess anthropometric variable in the postoperative period (p < 0.05). RESULTS: 77 patients (24%) were included in Group 1 (G1), 101 (32%) in Group 2 (G2), and 141 (44%) in Group 3 (G3). The majority of patients, 71.7% in G1, 82.8% in G2, and 70% in G3, showed high triglycerides (TG) before surgery. A decrease in weight loss was observed in all groups followed by an increase in body weight in G2 and G3 at 36, 48 and 60 months. Laboratory results for G1, G2 and G3 showed no significant differences between groups at baseline and during the post-operative period. CONCLUSION: Our results suggest that weight regain after RYGB has no significant impact on the long-term evolution of the lipid profile and glycemia. PMID- 29791657 TI - Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system. AB - OBJECTIVE: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). SUBJECTS AND METHODS: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (>= 20 years of age) hospitalized from 2012--2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). RESULTS: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis --of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. CONCLUSION: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil. PMID- 29791658 TI - Self-report of psychological symptoms in hypoparathyroidism patients on conventional therapy. AB - OBJECTIVE: Hypoparathyroidism is characterized by parathyroid hormone deficiency and hypocalcemia. It has been demonstrated that these patients may also present psychiatric symptoms and decrease of quality of life. The aims of this study were to evaluate the presence of psychopathological symptoms in a cohort of patients with hypoparathyroidism and compare to a control group. SUBJECTS AND METHODS: Patients were submitted to a cross-sectional Symptom Checklist-90-R (SCL-90-R) questionnaire that evaluates psychopathological symptoms by means of the Global Severity Index (GSI), Positive Symptoms Total (PST) and Positive Symptom Distress Index (PSDI). A score based in the positive symptoms was calculated (T-score). The test group was composed of patients with hypoparathyroidism, and control by thyroidectomized patients without hypoparathyroidism. A correlation between the presence of psychological symptoms and clinical features was analyzed. RESULTS: The study included 57 patients with a mean age of 51.1 +/- 16.4 years; 20 as a control and 37, test group. There were no differences between groups regarding gender, mean age and age at diagnose. Hypoparathyroidism patients presented higher GSI index than the control group (p = 0.038). Mean T-score of the test group was as elevated as 58.2 +/- 5.3 (reference range < 55). No correlation of the number of psychological symptoms to clinical and laboratorial parameters was observed. CONCLUSION: Patients with hypoparathyroidism attending our outpatient clinics presented an increase in the number of self-report of psychological symptoms when compared with a control group. However, no correlation with hypocalcemia and clinical parameters was observed. Future studies are necessary to evaluated if the absence of PTH play a role on it. PMID- 29791659 TI - Serum TSH level stability after 5 years in euthyroid adults at low risk for thyroid dysfunction. AB - OBJECTIVE: To evaluate changes in thyroid function after 5 years, the interval proposed for new assessment, in initially euthyroid adults. SUBJECTS AND METHODS: Initially, 1,426 apparently healthy adults considered low risk for thyroid dysfunction, were evaluated by measurement of TSH. After 5 years, 1,215 (85.2%) subjects were reevaluated. RESULTS: After 5 years, four subjects were receiving levothyroxine (L-T4) replacement therapy and 25 others had TSH > 4 mIU/L, only two of them with TSH > 10 mIU/L. All of these subjects had TSH > 3 mIU/L in the initial evaluation. During reassessment, none of the subjects had been or was treated for hyperthyroidism and 22 had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). Nineteen of these subjects had TSH <= 0.6 mIU/L in the initial evaluation. Among the 1,098 subjects with TSH between 0.6 and 3 mIU/L in the initial evaluation, reassessment showed that none of the subjects was using L-T4; only three had TSH > 4 mIU/L (none of them > 10 mIU/L); none had been or was treated for hyperthyroidism, and only three had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). These results did not differ between men and women or between subjects <= 60 and > 60 years. CONCLUSION: Repeat TSH measurement within an interval of only 5 years would not be cost-effective in adults without known thyroid disease or risk factors for dysfunction who exhibit TSH between 0.6 and 3 mIU/L. PMID- 29791661 TI - Effectiveness and safety of carbohydrate counting in the management of adult patients with type 1 diabetes mellitus: a systematic review and meta-analysis. AB - OBJECTIVE: This study aimed to evaluate the effectiveness and safety of carbohydrate counting (CHOC) in the treatment of adult patients with type 1 diabetes mellitus (DM1). MATERIALS AND METHODS: We performed a systematic review of randomized studies that compared CHOC with general dietary advice in adult patients with DM1. The primary outcomes were changes in glycated hemoglobin (HbA1c), quality of life, and episodes of severe hypoglycemia. We searched the following electronic databases: Embase, PubMed, Lilacs, and the Cochrane Central Register of Controlled Trials. The quality of evidence was analyzed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 3,190 articles were identified, and two reviewers independently screened the titles and abstracts. From the 15 potentially eligible studies, five were included, and 10 were excluded because of the lack of randomization or different control/intervention groups. Meta-analysis showed that the final HbA1c was significantly lower in the CHOC group than in the control group (mean difference, random, 95% CI: -0.49 (-0.85, -0.13), p = 0.006). The meta-analysis of severe hypoglycemia and quality of life did not show any significant differences between the groups. According to the GRADE, the quality of evidence for severe hypoglycemia, quality of life, and change in HbA1c was low, very low, and moderate, respectively. CONCLUSION: The meta-analysis showed evidence favoring the use of CHOC in the management of DM1. However, this benefit was limited to final HbA1c, which was significantly lower in the CHOC than in the control group. PMID- 29791660 TI - Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer. AB - Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC. PMID- 29791662 TI - Graves' ophthalmopathy: low-dose dexamethasone reduces retinoic acid receptor alpha gene expression in orbital fibroblasts. AB - OBJECTIVE: Graves' ophthalmopathy (GO) is an autoimmune disease that leads to ocular proptosis caused by fat accumulation and inflammation, and the main treatment is corticosteroid therapy. Retinoid acid receptor-alpha (RARalpha) seems to be associated with inflammation and adipocyte differentiation. This study aimed to assess the effect of glucocorticoid treatment on orbital fibroblasts of GO patient treated or not with different glucocorticoid doses. MATERIALS AND METHODS: Orbital fibroblasts collected during orbital decompression of a female patient with moderately severe/severe GO were cultivated and treated with 10 nM and 100 nM dexamethasone (Dex). rRARalpha gene expression in the treated and untreated cells was then compared. RESULTS: Fibroblast RARalpha expression was not affected by 100 nM Dex. On the other hand, RARalpha expression was 24% lower in cells treated with 10 nM Dex (p < 0.05). CONCLUSIONS: Orbital fibroblasts from a GO patient expressed the RARalpha gene, which was unaffected by higher, but decreased with lower doses of glucocorticoid. PMID- 29791664 TI - [Competition in the arts of midwifery in the city of Rio de Janeiro from 1835 to 1900]. AB - The article discusses competition between midwives and doctors offering birth related services in the city of Rio de Janeiro from 1835 to 1900. The research analyzed minutes from meetings, textbooks on births, and terms from qualification examinations for physicians, surgeons, apothecaries, and midwives at the Rio de Janeiro Medical School (Faculdade de Medicina do Rio de Janeiro), as well as announcements by and advertisements for doctors and midwives in columns featuring advertisements and useful recommendations in the Jornal do Commercio newspaper. An increase in the number of delivery physicians, and their scientific discourses led midwives to feel an obligation to diversify their clientele, consequently establishing themselves and working in lower-class and inhospitable areas. PMID- 29791663 TI - [Evolution and revolution: the anarchist geographers Elisee Reclus and Petr Kropotkin and their connection to modern science in the nineteenth and twentieth centuries]. AB - This text examines the construction of a line of scientific thinking by a group of anarchist geographers who were active in the nineteenth and twentieth centuries, most famously represented by Elisee Reclus and Petr Kropotkin. The members of this network were simultaneously intellectuals and activists, and the originality of their scientific production stands out in comparison with the science of that time. They were also interested in disciplines such as sociology, anthropology, and pedagogy, and used the scientific tools from the leading intellectual trains of thought of that era (such as positivism and especially evolutionism) in an attempt to reach different conclusions that did not justify social inequalities, but rather could be used to construct a fairer society. PMID- 29791666 TI - Prevalence of polymorphisms in the ANKK1, DRD2, DRD3 genes and metabolic syndrome in refractory schizophrenia. AB - OBJECTIVE: to estimate the prevalence of TaqIA, -141C and rs6280 polymorphisms of the ANKK1, DRD2 and DRD3 genes and evaluate their association with the occurrence of metabolic syndrome in patients with refractory schizophrenia. METHOD: cross sectional study conducted in the Extended Western Region of Minas Gerais, with refractory schizophrenic patients using the antipsychotic clozapine. Sociodemographic, clinical, anthropometric, biochemical and genetic data were collected. Univariate analysis of the data was performed. RESULTS: seventy-two patients participated in the study and the occurrence of Metabolic Syndrome was observed in 47.2% of them. There was no association between Metabolic Syndrome and the studied polymorphisms. There was a statistically significant difference in the low HDL parameter with homozygous genotype for the C allele of the -141C polymorphism of the DRD2 gene. CONCLUSION: a high prevalence of MS was evidenced. The -141C polymorphism was associated with low HDL. Genetic analysis and identification of metabolic alterations in this group of patients can guide drug treatment and provide a better quality of life. PMID- 29791665 TI - Serial album validation for promotion of infant body weight control. AB - OBJECTIVE: to validate the content and appearance of a serial album for children aged from 7 to 10 years addressing the topic of prevention and control of body weight. METHOD: methodological study with descriptive nature. The validation process was attended by 33 specialists in educational technologies and/or in excess of infantile weight. The agreement index of 80% was the minimum considered to guarantee the validation of the material. RESULTS: most of the specialists had a doctoral degree and a graduate degree in nursing. Regarding content, illustrations, layout and relevance, all items were validated and 69.7% of the experts considered the album as great. The overall agreement validation index for the educational technology was 0.88. Only the script-sheet 3 did not reach the cutoff point of the content validation index. Changes were made to the material, such as title change, inclusion of the school context and insertion of nutritionist and physical educator in the story narrated in the album. CONCLUSION: the proposed serial album was considered valid by experts regarding content and appearance, suggesting that this technology has the potential to contribute in health education by promoting healthy weight in the age group of 7 to 10 years. PMID- 29791667 TI - Good practices in normal childbirth: reliability analysis of an instrument by Cronbach's Alpha. AB - OBJECTIVES: to analyze the internal consistency of the evaluation instrument of the adherence to the good practices of childbirth and birth care in the professionals, through Cronbach's Alpha Coefficient for each of the dimensions and for the total instrument. METHOD: this is a descriptive and cross-sectional study performed in obstetric centers of eleven public hospitals in the Federal District, with a questionnaire applied to 261 professionals who worked in the delivery care. RESULTS: The study was attended by 261 professionals, 42.5% (111) nurses and 57.5% (150) physicians. The reliability evaluation of the instrument by the Cronbach Alfa resulted in 0.53, 0.78 and 0.76 for dimensions 1, 2 and 3, after debugging that resulted in the exclusion of 11 items. CONCLUSIONS: the instrument obtained Cronbach's alpha of 0.80. There is a need for improvement in the items of dimension 1 that refer to attitudes, knowledge, and practices of the organization of the network of care to gestation, childbirth, and birth. However, it can be applied in the way it is used to evaluate practices based on scientific evidence of childbirth care. PMID- 29791668 TI - Phlebitis and infiltration: vascular trauma associated with the peripheral venous catheter. AB - OBJECTIVE: to determine the incidence rate and risk factors for the nursing sensitive indicators phlebitis and infiltration in patients with peripheral venous catheters (PVCs). METHOD: cohort study with 110 patients. Scales were used to assess and document phlebitis and infiltration. Socio-demographic variables, clinical variables related to the PVC, medication and hospitalization variables were collected. Descriptive and inferential analysis and multivariate logistic models were used. RESULTS: the incidence rate of phlebitis and infiltration was respectively 43.2 and 59.7 per 1000 catheter-days. Most PVCs with these vascular traumas were removed in the first 24 hours. Risk factors for phlebitis were: length of hospital stay (p=0.042) and number of catheters inserted (p<0.001); risk factors for infiltration were: piperacillin/tazobactan (p=0.024) and the number of catheters inserted (p<0.001). CONCLUSION: the investigation documented the incidence of nursing-sensitive indicators (phlebitis and infiltration) and revealed new risk factors related to infiltration. It also allowed a reflection on the nursing care necessary to prevent these vascular traumas and on the indications and contraindications of the PVC, supporting the implementation of the PICC as an alternative to PVC. PMID- 29791669 TI - Transcultural adaptation and new proposal for the nursing outcome, Physical condition (2004). AB - OBJECTIVES: cross-culturally adapt to the Spanish context and make a new proposal for the nursing outcome, Physical Condition (2004), of the Nursing Outcomes Classification (NOC) for its precise use in clinical practice. METHOD: a cross cultural adaptation study and a proposal for the nursing outcome, Physical Condition, was conducted and supported by the opinion of 26 experts. The data was obtained through an electronic form, and a quantitative analysis was conducted, using the SPSS software. RESULTS: the version adapted to the Spanish context was obtained and the proposal of the outcome, Physical Condition, received agreement from 26 experts, with a mean score greater than 7.6 for adequacy of the outcome definition and its indicators, and 8.5 for the relevance of the indicators. CONCLUSIONS: the version adapted to the Spanish context and a new proposal for Physical Condition were obtained. The results obtained indicate a high level of adequacy and relevance, an instrument of great utility in the clinic, and research was obtained to evaluate the interventions directed to the improvement of the physical condition. PMID- 29791670 TI - Cross-cultural validation of the Child Adolescent Teasing Scale for Colombian students. AB - OBJECTIVE: to carry out the cross-cultural validation of the instrument "Child Adolescent Teasing Scale" for the Colombian student population. METHOD: methodological study carried out with students aged 8 to 15, from public and private educational institutions in the municipality of Ibague, Colombia. The form for the characterization of students and the Child Adolescent Teasing Scale were used. RESULTS: the cross-cultural adaptation process was organized in seven steps: comparison of the Spanish version of the instrument with the original English version, back-translation, consensus version, face validity and terminology adjustment by students, face and content validity by experts, assessment committee for the final version, pilot test and reliability. CONCLUSION: the version adapted to the Spanish spoken in Colombia of the Child Adolescent Teasing Scale (Escala de burlas para ninos y adolescentes), which assesses the frequency and distress caused by teasing, showed desirable results in terms of validity and reliability. PMID- 29791671 TI - Validation of a moral distress instrument in nurses of primary health care. AB - OBJECTIVE: to validate an instrument to identify situations that trigger moral distress in relation to intensity and frequency in primary health care nurses. METHOD: this is a methodological study carried out with 391 nurses of primary health care, applied to the Brazilian Scale of Moral Distress in Nurses with 57 questions. Validation for primary health care was performed through expert committee evaluation, pre-test, factorial analysis, and Cronbach's alpha. RESULTS: there were 46 questions validated divided into six constructs: Health Policies, Working Conditions, Nurse Autonomy, Professional ethics, Disrespect to patient autonomy and Work Overload. The instrument had satisfactory internal consistency, with Cronbach's alpha 0.98 for the instrument, and between 0.96 and 0.88 for the constructs. CONCLUSION: the instrument is valid and reliable to be used in the identification of the factors that trigger moral distress in primary care nurses, providing subsidies for new research in this field of professional practice. PMID- 29791672 TI - Jacobson and Truax Method: evaluation of the clinical effectiveness of a home care program after prostatectomy. AB - OBJECTIVE: to exemplify the applicability of the Jacobson and Truax Method in a nursing intervention study that analyzed the effectiveness of a home care teaching program after radical prostatectomy. METHOD: this is a descriptive study concerning the applicability of the Jacobson and Truax Method in the data analysis of a clinical trial. The intervention consisted of a teaching program for hospital discharge after radical prostatectomy through oral guidance, writing, and telephonic reinforcement. Thirty-four men participated in the intervention group and 34 men participated in the control group. A reliable index of change and clinical significance was calculated for the knowledge variable in both groups. Scatterplots were presented to demonstrate the effectiveness of the method. RESULTS: for 30 individuals in the intervention group, the intervention presented clinically relevant change than in knowledge. In the control group, none of the 34 individuals presented clinical significance of the results related to this variable, that is, the statistical significance identified by the inferential tests did not have clinically relevant changes in the knowledge variable. CONCLUSION: the educational intervention carried out through the combination of oral, written and telephone counseling was shown to be clinically effective in improving knowledge about home care. PMID- 29791673 TI - Development of a clinical protocol for detection of cervical cancer precursor lesions. AB - OBJECTIVE: to develop and validate the content of a clinical protocol aimed at prevention of cervical cancer in primary care. METHOD: technological research according to the steps: (1) submission of the project to the research ethics committee; (2) bibliographic survey; (3) elaboration of the clinical protocol; and (4) content validation. In the third step, the information was collected through bibliographic research and gynecology specialists were consulted. For the final step, four judges were selected to evaluate the clinical protocol according to AGREE 2. Domains that reached the minimum level of agreement of 75% in the scores were considered validated. RESULTS: the scores obtained in each domain of the instrument were as follows: domain 1 (scope and purpose) = 87.5%; domain 2 (stakeholder involvement) = 83.3%; domain 3 (development rigor) = 79.7%; domain 4 (clarity of presentation) = 76.3%; domain 5 (applicability) = 78.1%; and domain 6 (editorial independence) = 85.4. CONCLUSION: the clinical protocol proved to be a validated material with scores above the minimum required. The protocol obtained positive recommendations with modifications and went through adjustments in order to make it more effective. PMID- 29791674 TI - Disseminating health evidence summaries to increase evidence use in health care. AB - OBJECTIVE: To verify whether an intervention based on disseminating health evidence summaries by e-mail to health professionals increases access to health evidence databases, and whether health professionals intend to apply the evidence received by e-mail in their clinical practice. METHODS: This quantitative study started with a survey to collect demographic data and patterns of access to health evidence databases. It was followed by a longitudinal intervention, over 48 weeks, that disseminated 143 health evidence summaries to 339 health professionals with higher education degree who work in the Brazilian Unified Health System. In the longitudinal intervention phase, health professionals voluntarily assessed the received health evidence summaries using the information assessment method. Finally, the study concluded with a survey to identify changes in accessing health evidence databases. RESULTS: Of the 339 Brazilian health professionals participating in this research, 90 (26.5%) answered the initial and final surveys. After 48 weeks, there was an increase in the use of health evidence databases; 186 (54.9%) participants submitted 7,942 assessments of health evidence summaries, which were relevant for patient care in 5,409 (68%) assessments. CONCLUSIONS: The dissemination of health evidence summaries by e mail to health professionals in Brazil increases the reported use of evidence in clinical practice. PMID- 29791675 TI - Development of a Diet Quality Index Adapted for Pregnant Women. AB - OBJECTIVE: To develop a Diet Quality Index Adapted for Pregnant Women (IQDAG) and to evaluate its relation with the characteristics of women treated at the Brazilian Unified Health System. METHODS: The data on food intake come from a cross-sectional study carried out with 785 adult pregnant women in the city of Ribeirao Preto, state of Sao Paulo, Brazil, between 2011 and 2012. The index was based on the recommendations of the Brazilian Ministry of Health, previous national dietary indexes, and the new Dietary Guidelines for the Brazilian Population. We used the ANOVA, Kruskal-Wallis, and chi-square tests to describe the quality of the diet according to the characteristics of the mother. RESULTS: The IQDAG has nine components, and it is represented by three food groups (in servings/1,000 kcal), five nutrients, and a moderator component. A high proportion of pregnant women reached the maximum score for the components of legumes and vegetables. However, few women reached the maximum score for consumption of fresh fruits, fiber, omega-3, calcium, folate, iron, and ultra processed foods. We verified a better quality of diet among older and eutrophic pregnant women who reported practicing more physical activity and taking dietary supplements. We also observed the highest index score among women with higher intake of carbohydrates, proteins, vitamins C, E, and A, and minerals calcium, folate, and iron, as well as among those with lower intake of total fats and saturated fats. CONCLUSIONS: This dietary index is unprecedented in incorporating the recommendation of the new Dietary Guidelines for the Brazilian Population regarding the moderation of the consumption of ultra-processed foods. It was useful in evaluating the quality of the diet of pregnant women and we verified a higher score among older and eutrophic women who reported a healthy lifestyle. Strategies are needed to promote a higher consumption of fresh fruits, foods high in fiber, omega-3, calcium, folate, iron, and minimally processed foods in pregnant women. PMID- 29791676 TI - Suicide in Brazilian indigenous communities: clustering of cases in children and adolescents by household. AB - OBJECTIVE To estimate age and sex-specific suicide rates, compare suicide rates between indigenous communities, and quantify the frequency of intrafamilial suicide clustering. METHODS We performed a retrospective cohort study involving 14,666 indigenous individuals in reservations in Dourados, state of Mato Grosso do Sul, Brazil, from 2003 through 2013 using national and local census. RESULTS The overall suicide rate was 73.4 per 100,000 person-years. Adolescent males aged 15-19 and girls aged 10-14 had the highest rates for each sex at 289.3 (95%CI 187.5-391.2) and 85.3 (95%CI 34.9-135.7), respectively. Comparing the largest reservations, Bororo had a higher suicide rate than Jaguapiru (RR = 4.83, 95%CI 2.85-8.16) and had significantly lower socioeconomic indicators including income and access to electricity. Nine of 19 suicides among children under 15 occurred in household clusters. Compared with adult suicides, a greater proportion of child (OR = 5.12, 95%CI 1.89-13.86, p = 0.001) and adolescent (OR = 3.48, 95%CI 1.29-9.44, p = 0.017) suicides occurred within household clusters. CONCLUSIONS High rates of suicide occur among children and adolescents in these indigenous reservations, particularly in poor communities. Nearly half of child suicides occur within household clusters. These findings underscore the need for broad public health interventions and focused mental health interventions in households following a suicide. PMID- 29791677 TI - Multifactorial intervention for diabetes control among older users of insulin. AB - OBJECTIVE: To evaluate if the closer follow-up with the supply of insulin pens and the measurement of capillary blood glucose improve the management of older patients with type 2 diabetes without adequate glycemic control despite extensive therapy. METHODS: This is a prospective, non-randomized, quasi-experimental study. We have included 45 patients over 60 years old, from both sexes, with glycated hemoglobin (HbA1c) > 8.5% using oral hypoglycemic agents and insulin. The intervention consisted of monthly medical visits, with the provision of insulin pens and strips for blood glucose measurement. All patients received insulin pen, refills of Neutral Protamine Hagedorn and regular insulin, needles for the pen, blood glucose meter, and capillary blood glucose tests (three tests/day). Treatment was adjusted with the same endocrinologist monthly for six months. Glycated hemoglobin was measured at baseline and 12 and 24 weeks after intervention. RESULTS: Glycated hemoglobin at baseline was 10.34% (SE = 0.22%) and 8.54% (SE = 0.24%, p < 0.001) and 8.09% (SE = 0.21%, p < 0.001) at 12 and 24 weeks after intervention, respectively, with a significant reduction from baseline. CONCLUSIONS: More frequent medical visits, with treatment inputs including the use of insulin pens and self-monitoring, have improved glycemic control (reduction of 2.25% in HbA1C, on average, at 24 weeks of follow-up). Our data support a change in the management and medical behavior of older patients with chronically decompensated diabetes. PMID- 29791678 TI - Utilization of basic health units of FHS according to private health insurance. AB - OBJECTIVE To describe the utilization of basic health units according to coverage by discount card or private health insurance. METHODS Household survey in the area covered by Family Health Strategy in Pelotas, state of Rio Grande do Sul, Brazil, from December 2007 to February 2008, with persons of all age groups. The frequency of (medical or non-medical) healthcare seeking at the basic health units in the last six months and the prevalence of basic health unit utilization for the last medical consultation (in case it had been performed up to six months before, for a non-routine reason) were analyzed by Poisson regression adjusted for the sampling design. RESULTS Of the 1,423 persons, 75.6% had no discount card or private health insurance. The average frequency of (medical or non-medical) healthcare seeking was 1.6 times in six months (95%CI 1.3-2.0); this frequency was 55.8% lower (p < 0.001) among privately insured persons compared to those with no discount card or private health insurance. Among the last medical consultations, 35.8% (95%CI 25.4-47.7) had been performed at the basic health units; this prevalence was 36.4% lower (p = 0.003) among persons covered by discount card and 87.7% lower (p = 0.007) among privately insured persons compared to those without both coverages. CONCLUSIONS Private health insurance and, to a lesser degree, discount card coverage, are related to lower utilization of basic health units. This can be used to size the population under the accountability of each Family Health Strategy team, to the extent that community health workers are able to differentiate discount card from PHI during family registration. PMID- 29791679 TI - School health promotion and use of drugs among students in Southern Brazil. AB - OBJECTIVE: To analyze the relationship between the health promotion conditions in schools and the consumption of alcohol and other drugs by students. METHODS: This is a cross-sectional study with a probabilistic sample of 3,464 students aged 12 to 17 from all schools of the cities of Lajeado and Sapiranga, state of Rio Grande do Sul, Brazil, and 53 managers from the same schools; the data was collected in 2012. Reports of the use of tobacco, alcohol, and illicit drugs in 2012 were used as outcomes, and the health promotion score in the school environment was used as the exposure of interest. We submitted the data to multilevel analysis. RESULTS: The prevalence of the annual use of tobacco was 9.8% (95%CI 8.8-10.8), alcohol was 46.2% (95%CI 44.5-47.8), and other drugs was 10.9% (95%CI 9.9-12.0). In the crude analysis, only the use of tobacco was associated with less health promoting schools (OR = 1.89, 95%CI 1.16-3.09) when compared to those with better conditions. This association lost statistical significance in the adjusted analysis (OR = 1.27, 95%CI 0.74-2.19). CONCLUSIONS: The effects of the school environment on the use of drugs, especially tobacco and alcohol, are manifested mainly by the individual and family conditions of the adolescents. PMID- 29791681 TI - THE INFLUENCE OF EDUCATIONAL DANCE ON THE MOTOR DEVELOPMENT OF CHILDREN. AB - OBJECTIVE: The purpose of this study was to compare the motor development of children who practiced educational dance with the motor development of children who did not practice it and to verify the results obtained after six to eight months after the end of the intervention. METHODS: The study was carried out with 85 children enrolled in the first year of elementary school in two schools located in the south of Sao Paulo city (Sao Paulo, Brazil). Children were randomized by lot in two groups (intervention and control). Children with intellectual and/or physical disabilities and the premature ones were excluded from the analysis. The two groups had their motor development evaluated in three moments: before the intervention, after the intervention and six to eight months after the end of the intervention. The intervention group participated in an educational dance class program for seven months. Control and intervention groups were compared by chi-square and t-test. RESULTS: Children who participated in the educational dance program, compared to children who did not, achieved significant gains in their general motor development and on the following bases: balance, fine motor and overall praxis. CONCLUSIONS: Educational dance helped the children's motor development, and the results were partially maintained months after the end of the intervention. PMID- 29791682 TI - BODY DISSATISFACTION, PHYSICAL ACTIVITY, AND SEDENTARY BEHAVIOR IN FEMALE ADOLESCENTS. AB - OBJECTIVE: To evaluate the association of body image with physical activity level, body composition, and sedentary behavior (SB) of female adolescents. METHODS: Exploratory cross-sectional study conducted with 120 female adolescents aged between 14-19 years, from the city of Vicosa, Minas Gerais, Southeast Brazil. Body image was evaluated with a Body Silhouette Scale (BSS) and a Body Shape Questionnaire (BSQ). Weight, height, and waist circumference values were analyzed, as well as the waist-to-height ratio and body fat percentage. The physical activity level (PAL) was assessed by 24-hour Physical Activity Recall and SB by screen time, that is, time spent in front of a TV, playing video game, on the computer and using tablets, and, separately, the cell phone time. RESULTS: Mean age was 16.5+/-1.5 years, and most adolescents were eutrophic (77.6%), sedentary/low PAL (84.2%), with high screen time (85.2%) and cell phone time (58.7%). Body dissatisfaction was stated in 40.6% of BSQ and 45.8% of BSS evaluations. Body distortion was identified in 52.9% of participants. All body composition measures, along with cell phone time and PAL, were associated with body dissatisfaction, the more active adolescents presenting higher levels of dissatisfaction. CONCLUSIONS: This study concluded that female adolescents with higher cell phone time also present higher body dissatisfaction, as well as the most physically active ones. All body composition measurements were associated with body dissatisfaction, mainly body mass index, waist circumference, and waist to-height ratio. PMID- 29791683 TI - The T-loop in details. AB - INTRODUCTION: The T-loop as designed by Burstone is a space closure spring used in the rational application of orthodontic biomechanics. Despite the diversity of studies, there is still no consensus on the optimal parametric characteristics for its conformation. OBJECTIVE: This study aimed at reviewing the literature on the force systems released by different conformations of the T-loop, according to the type of anchorage and the main characteristics and factors that influence them. RESULTS: Comparing the studies, the need for standardization was perceived in the methodology to shape the loops, regarding the variables that influence the force system. Most of the experimental studies with this loop do not report the vertical movement, nor the steps and angles that occur in the brackets. Clinical studies have obtained more variable results in relation to vertical acting forces, considering the influence of chewing. CONCLUSION: There is great potential for future studies with this type of loop, especially using nickel titanium alloys, in order to achieve a pure translational movement without friction, with optimal and constant levels of force. PMID- 29791680 TI - Impact of stressful life events on central adiposity in the Pelotas Birth Cohort. AB - OBJECTIVE: To investigate how stressful life events and social support relate to central adiposity in Southern Brazil. METHODS: Data included information from 802 participants in the 1982 Pelotas Birth Cohort that was collect in 2004-2005 and 2006. Stratifying by sex, we studied self-reported stressful life events during the year before 2004-2005 in relation to change in waist circumference between 2004-2005 and 2006 and waist-to-hip ratio in 2006, using both bivariate and multivariate linear regression models. RESULTS: In adjusted models, the experience of stressful life events during the year before 2004-2005 predicted a change in waist circumference in 2006 in men and a change in both waist-to-hip ratio in 2006 and waist circumference between 2004-2005 and 2006 in women. Men who experienced two or more stressful events had on average a one centimeter increase in their waist circumference between 2004-2005 and 2006 (beta = 0.97, 95%CI 0.02-1.92), compared to those reporting no stressful events. For women, those who had one and those who had two or more stressful life events had over a 1 cm increase in their waist circumference from 2004-2005 to 2006 (beta = 1.37, 95%CI 0.17-2.54; beta = 1.26, 95%CI 0.11-2.40, respectively), compared to those who did not experience any stressful event. For both sexes, social support level was not significantly related to either waist-to-hip ratio or change in waist circumference, and it did not modify the association between stress and central adiposity. CONCLUSIONS: The experience of more than one stressful life event was associated with distinct indicators of central adiposity for men versus women. PMID- 29791684 TI - Stability of the anterior arm of three different Hyrax hybrid expanders: an in vitro study. AB - INTRODUCTION: The force applied to the teeth by fixed orthopaedic expanders has previously been studied, but not the force applied to the orthodontic mini implant (OMI) used to expand the maxilla with Hyrax hybrid expanders (HHE). OBJECTIVE: The aim of this article was to evaluate the clinical safety of the components (OMI, abutment and double wire arms) of three different force transmitting systems (FTS) for conducting orthopaedic maxillary expansion: Jeil Medical & Tiger DentalTM, MicrodentTM and OrtholoxTM. METHODS: For the realization of this in vitro study of the resistance to mechanical load, three different abutment types (bonded, screwed on, and coupling) and three different OMIs' diameters (JeilTM 2.5 mm, MicrodentTM 1.6 mm and OrtholoxTM 2.2 mm) were used. Ten tests for each of these three FTS were carried out in a static lateral load in artificial bone blocks (SawbonesTM) by a Galdabini universal testing machine, then comparing its performance. Comparisons of loads, deformations and fractures were carried out by means of radiographs of FTS components in each case. RESULTS: At 1- mm load and within the elastic deformation, FTS values ranged from 67 +/- 13 N to 183 +/- 48 N. Under great deformations, Jeil & TigerTM was the one who withstood the greatest loads, with an average 378 +/- 22 N; followed by MicrodentTM, with 201 +/- 18 N, and OrtholoxTM, with 103 +/- 10 N. At 3 mm load, the OMIs shaft bends and deforms when the diameter is smaller than 2.5 mm. The abutment fixation is crucial to transmit forces and moments. CONCLUSIONS: The present study shows the importance of a rigid design of the different components of HHEs, and also that HHEs would be suitable for maxillary expansion in adolescents and young adults, since its mean expansion forces exceed 120N. Furthermore, early abutment detachment or smaller mini-implants diameter would only be appropriate for children. PMID- 29791685 TI - Relationship between mandibular symphysis dimensions and mandibular anterior alveolar bone thickness as assessed with cone-beam computed tomography. AB - OBJECTIVE: To determine the relationship between symphysis dimensions and alveolar bone thickness (ABT) of the mandibular anterior teeth. METHODS: Cone beam computed tomography images of 51 patients were collected and measured. The buccal and lingual ABT of the mandibular anterior teeth was measured at 3 and 6 mm apical to the cemento-enamel junction (CEJ) and at the root apices. The symphysis height and width were measured. The symphysis ratio was the ratio of symphysis height to symphysis width. Kendall's tau correlation coefficient was used to determine the relationships between the variables at a 0.05 significance level. RESULTS: The mandibular anterior teeth lingual and apical ABT positively correlated with symphysis width (p<0.05). Moreover, these thicknesses negatively correlated with the symphysis ratio (p<0.05). Symphysis widths and ratios showed higher correlation coefficients with total and buccal apical ABT, compared with lingual ABT. Buccal ABT at 3 and 6 mm apical to the CEJ was not significantly correlated with most symphysis dimensions. The mean thickness of the buccal alveolar bone at the upper root half was only 0.2-0.6 mm, which was very thin, when compared with other regions. CONCLUSION: For mandibular anterior teeth, the apical alveolar bone and lingual alveolar bone tended to be thicker in patients with a wide and short symphysis, compared to those with a narrow and long symphysis. Buccal alveolar bone was, in general, very thin and did not show a significant relationship with most symphysis dimensions. PMID- 29791686 TI - Extruded upper first molar intrusion: Comparison between unilateral and bilateral miniscrew anchorage. AB - OBJECTIVE: The aim of his study was to evaluate the stress on tooth and alveolar bone caused by orthodontic intrusion forces in a supraerupted upper molar, by using a three-dimensional Finite Element Method (FEM). METHODS: A superior maxillary segment was modeled in the software SolidWorks 2010 (SolidWorks Corporation, Waltham, MA, USA) containing: cortical and cancellous bone, supraerupted first molar, periodontal tissue and orthodontic components. A finite element model has simulated intrusion forces of 4N onto a tooth, directed to different mini-screw locations. Three different intrusion mechanics vectors were simulated: anchoring on a buccal mini-implant; anchoring on a palatal mini implant and the association of both anchorage systems. All analyses were performed considering the minimum principal stress and total deformation. Qualitative analyses exhibited stress distribution by color maps. Quantitative analysis was performed with a specific software for reading and solving numerical equations (ANSYS Workbench 14, Ansys, Canonsburg, Pennsylvania, USA). RESULTS: Intrusion forces applied from both sides (buccal and palatal) resulted in a more homogeneous stress distribution; no high peak of stress was detected and it has allowed a vertical resultant movement. Buccal or palatal single-sided forces resulted in concentrated stress zones with higher values and tooth tipping to respective force side. CONCLUSION: Unilateral forces promoted higher stress in root apex and higher dental tipping. The bilateral forces promoted better distribution without evidence of dental tipping. Bilateral intrusion technique suggested lower probability of root apex resorption. PMID- 29791687 TI - An interview with Chris Chang. PMID- 29791688 TI - Periodontal clinical evaluation before and after surgically assisted rapid maxillary expansion. AB - INTRODUCTION: The surgically assisted rapid maxillary expansion is a procedure that reduces the resistance of the sutures correcting the posterior crossbite in adults. OBJECTIVE: The aim of this study was to evaluate the periodontal status of 17 adults submitted to this procedure. METHODS: The clinical attachment level (CAL), gingival recession, attached gingiva and bleeding were evaluated in maxillary first premolars and molars, central and lateral incisors of right and left sides before surgery, 5 days and 6 months after. Means, standard deviation, medians, minimum and maximum values were compared among the evaluations using the Friedman and McNemar tests. RESULTS: There was a statistically significant increase in CAL in the right central incisor, right and left premolars and right and left molars. There was a statistically significant increase in gingival recession in the right and left premolars and molars. The amount of attached gingiva significantly decreased in right premolars and right and left molars. There was increase in bleeding in most of the teeth. CONCLUSION: Results indicated that the surgically assisted rapid maxillary expansion might cause alterations in periodontal tissue. PMID- 29791689 TI - Tooth transposition: a multidisciplinary approach. AB - Tooth transposition is one of the most difficult dental anomalies to treat in the dental clinic. Several factors must be taken into account with a view of making the best decision. The aim of this study was to discuss treatment modalities for tooth transposition, their advantages and disadvantages. Additionally, it aims at presenting a clinical case of transposition between canine and lateral incisor in the upper quadrant on the right side. The treatment of choice was extraction of one transposed tooth. A multidisciplinary approach involving Orthodontics, Cosmetic Dentistry, and Periodontology was necessary to allow proper esthetic and functional outcomes to be achieved. PMID- 29791690 TI - Impact of two early treatment protocols for anterior dental crossbite on children's quality of life. AB - OBJECTIVE: To assess the impact of two early treatment protocols for anterior dental crossbite on children's quality of life. METHODS: Thirty children, 8 to 10 years of age, with anterior dental crossbite, participated in this study. Individuals were divided into two groups: Group 1 - 15 children undergoing treatment with an upper removable appliance with digital springs; Group 2 - 15 children undergoing treatment with resin-reinforced glass ionomer cement bite pads on the lower first molars. Quality of life was evaluated using the Brazilian version of the Child Perceptions Questionnaire (CPQ8-10), which contains four subscales: oral symptoms (OS), functional limitations (FL), emotional well-being (EW), and social well-being (SW). A higher score denotes a greater negative impact on children's quality of life. Children answered the questionnaire before treatment (T1) and twelve months after orthodontic treatment onset (T2). Descriptive statistics, the Wilcoxon test and analysis of covariance (ANCOVA) were performed. RESULTS: Children's mean age was 9.07 +/- 0.79 years in Group 1 and 9.00 +/- 0.84 years in Group 2. For Group 1, the FL and EW subscale scores and the overall CPQ8-10 were significantly higher in T1 as compared to T2 (p= 0.004, p= 0.012 and p= 0.015, respectively). For Group 2, there were no statistically significant differences. The ANCOVA showed no significant difference regarding quality of life at T2 between groups, after controlling for quality of life measures at T1. CONCLUSIONS: The difference regarding the impact on quality of life between groups is not related to the protocol used. PMID- 29791691 TI - Evaluation of miniscrew angulation in the posterior maxilla using cone-beam computed tomographic image. AB - OBJECTIVE: This study aimed at evaluating whether changes in the insertion angle is a determining factor in the positioning of the miniscrews body in a region with larger interradicular space in the posterior maxilla. METHODS: Analysis of 60 posterior maxillary quadrants were made using images obtained by means of cone beam computed tomographic image (CBCT), with 0.076-mm voxel, which presented a real miniscrew inserted in the mesial region of the maxillary first molars, serving as reference point for the placement of the virtual miniscrews. Measurements of the distances between roots were made in three points on the body of the virtual miniscrews (A, B and C), at four different angulations, 70o, 60o, 50o and 40o (T1 to T4), in relation to the long axis of the second premolar. This evaluation was made in four groups, selected in accordance with the disposition of the roots of the second premolars and first molars: Group 1 (all types of roots), Group 2 (convergent roots), Group 3 (divergent roots) and Group 4 (parallel roots). RESULTS: There were no statistically significant differences in the measurements of points A, B and C, at the different angles (70o, 60o, 50o and 40o) and in the different groups (p > 0.05). CONCLUSIONS: Changes in the insertion angle is not a determinant factor in the positioning of miniscrews body in regions with larger interradicular space in posterior maxilla. PMID- 29791692 TI - Prosthetic, orthodontic and implant-supported rehabilitation of five maxillary anterior teeth with alveolar bone loss. AB - INTRODUCTION: Treatment of maxillofacial injuries is complex and requires the establishment of a comprehensive and accurate diagnosis and correct treatment planning. OBJECTIVE: The objective of this case report was to describe the re treatment of a 27-year-old woman who was involved in a severe car accident that resulted in the loss of five anterior teeth and alveolar bone, and whose previous orthodontic and surgical treatments had been unsuccessful. CASE REPORT: In this case, the space for the missing mandibular molar was reopened to allow for rehabilitation. The positions of the mandibular incisors were improved. The right mandibular canine was moved to the mesial, allowing for correction of the Class II canine relationship on that side, and implants were placed to replace the maxillary anterior teeth. CONCLUSION: Anterior aesthetic and functional rehabilitation using a multidisciplinary approach was essential to improve the patient's facial aesthetics, to obtain great improvement in function and to achieve occlusal stability after 2 years of follow-up. PMID- 29791693 TI - Decoronation followed by dental implants placement: fundamentals, applications and explanations. AB - Dental arches areas with teeth presenting dentoalveolar ankylosis and replacement root resorption can be considered as presenting normal bone, in full physiological remodeling process; and osseointegrated implants can be successfully placed. Bone remodeling will promote osseointegration, regardless of presenting ankylosis and/or replacement root resorption. After 1 to 10 years, all dental tissues will have been replaced by bone. The site, angulation and ideal positioning in the space to place the implant should be dictated exclusively by the clinical convenience, associated with previous planning. One of the advantages of decoronation followed by dental implants placement in ankylosed teeth with replacement resorption is the maintenance of bone volume in the region, both vertical and horizontal. If possible, the buccal part of the root, even if thin, should be preserved in the preparation of the cavity for the implant, as this will maintain gingival tissues looking fully normal for long periods. In the selection of cases for decoronation, the absence of microbial contamination in the region - represented by chronic periapical lesions, presence of fistula, old unconsolidated root fractures and active advanced periodontal disease - is important. Such situations are contraindications to decoronation. However, the occurrence of dentoalveolar ankylosis and replacement resorption without contamination should neither change the planning for implant installation, nor the criteria for choosing the type and brand of dental implant to be used. Failure to decoronate and use dental implants has never been reported. PMID- 29791694 TI - Filling Open Screw Holes in the Area of Metaphyseal Comminution Does Not Affect Fatigue Life of the Synthes Variable Angle Distal Femoral Locking Plate in the AO/OTA 33-A3 Fracture Model. AB - INTRODUCTION: The aim of this study is to evaluate the biomechanical effect of filling locking variable angle (VA) screw holes at the area of metaphyseal fracture comminution in a Sawbones(r) (Sawbones USA, Vashon, Washington) model (AO/OTA 33A-3 fracture) using a Synthes VA locking compression plate (LCP) (Depuy Synthes, Warsaw, Indiana). MATERIALS AND METHODS: Seven Sawbones(r) femur models had a Synthes VA-LCP placed as indicated by the manufacturers technique. A 4cm osteotomy was then created to simulate an AO/OTA 33-A3 femoral fracture pattern with metaphyseal comminution. The control group consisted of four constructs in which the open screw holes at the area of comminution were left unfilled; the experimental group consisted of three constructs in which the VA screw holes were filled with locking screws. One of the control constructs was statically loaded to failure at a rate of 5mm/min. A value equal to 75% of the ultimate load to failure was used as the loading force for fatigue testing of 250,000 cycles at 3Hz. Cycles to failure was recorded for each construct and averages were compared between groups. RESULTS: The average number of cycles to failure in the control and experimental groups were 37524+/-8187 and 43304+/-23835, respectively (p=0.72). No significant difference was observed with respect to cycles to failure or mechanism of failure between groups. In all constructs in both the control and experimental groups, plate failure reproducibly occurred with cracks through the variable angle holes in the area of bridged comminution. CONCLUSIONS: The Synthes VA-LCP in a simulated AO/OTA 33-A3 comminuted metaphyseal femoral fracture fails in a reproducible manner at the area of comminution through the "honeycomb" VA screw holes. Filling open VA screw holes at the site of comminution with locking screws does not increase fatigue life of the Synthes VA LCP in a simulated AO/OTA 33-A3 distal femoral fracture. Further studies are necessary to determine whether use of this particular plate is contraindicated when bridging distal femoral fractures with metaphyseal comminution. PMID- 29791695 TI - Current Strategies to Prevent Iatrogenic Ureteral Injury During Colorectal Surgery. AB - Iatrogenic ureteral injuries are a source of major concern among surgeons performing colorectal procedures. Although they are uncommon, these lesions lead to severe morbidity and long-term functional disabilities, as well as an increase in mortality, hospital stay, and cost. The laparoscopic approach has gained popularity in the field of colorectal surgery and is associated with improved global postoperative outcomes. However, it is also considered to increase the risk of ureteral injury when compared to open surgery, especially during left colonic and rectal resections. To overcome these difficulties, surgical techniques have been improved over time through standardization of both open and laparoscopic procedures. However, these techniques are not infallible, and, in difficult cases, instrumental aids such as preoperative ureteral stenting may be used. To substitute the reduced haptic feedback in laparoscopic surgery, lighted stents have been developed. Unfortunately, prophylactic stenting, whether standard or lighted, is also associated with its own morbidity and its benefit risk ratio remains highly controversial. To enhance the surgeon's visualization capabilities, augmented reality technologies have been developed. Near-infrared fluorescence and hyperspectral imaging are two promising techniques, which have been tested both in the preclinical and clinical settings. Early results show that these technologies could improve our ability to identify and protect the ureters, although technical limitations remain to be solved. Reviewing the current literature, this article aims to evaluate pre- and intraoperative techniques to identify the ureters and potentially to avoid iatrogenic injury. In addition, future trends are explored. PMID- 29791696 TI - Monocenter Experience with 532 Nm-Laser Photoselective-Vaporization of the Prostate by GreenLight XPS? Laser: Is It Really an Endourological Joker Card? AB - INTRODUCTION: In our study, we reported on our monocenter experience with GreenLight (GL) Xcelerated Performance System (XPS)? /MoXy? laser fiber (American Medical Systems Inc., Minnetonka, Minnesota), examining its efficacy, safety, and its ability to effectively treat lower urinary tract symptoms (LUTS) in benign prostate obstruction (BPO). We also explored and compared the three different endoscopic approaches used for GL treatment of benign prostatic hyperplasia (BPH), standard photovaporization (PVP), anatomical PVP, and GreenLight XPS? enucleation of the prostate. MATERIALS AND METHODS: Between February 2013 and April 2017, 140 patients, with an average age of 67.7 years (range 47-85), were treated using the XPS?/MoXy? system in a single-operative urologic center. The data were retrospectively analyzed with an assessment of the main intra- and postoperative outcomes at three, six, 12, and 18 months comparing both subjective (international prostate symptom score [IPSS]) and objective (uroflow [Qmax] parameters and prostate volume) parameters to the preoperative data. Patients underwent standard PVP, anatomical PVP, or prostate photo-selective en-bloc enucleation (PEBE) according to surgeon preferences. RESULTS: Median prostate volume (MPV) and prostate-specific antigen (PSA) were 69cc and 3.24 ng/dl, respectively. An indwelling catheter, at the time of surgery, was observed in 15% of men. Median operative-laser time and energy applied were 56.4 minutes, 26.5 minutes, and 245813 kJ. Outpatient surgery was feasible with median length of stay at 48 hours. Significant improvement in IPSS and Qmax are observed at all endpoints. No significant intraoperative complications were reported. When stratifying postoperative complications according to the Cavien-Dindo classification, only two cases of high-degree emerged (grades III-IV). CONCLUSION: Our data confirm that in treating men with symptomatic benign prostate disease, the GreenLight XPS?/MoXy? laser fiber is safe and able to achieve challenging results in terms of clinical outcomes and prostate volume reduction. Balance between functional outcomes and complications was great without statistically significant differences, in terms of outcomes, between the different surgical techniques. PMID- 29791697 TI - Total Laparoscopic Hysterectomy in the Setting of Prior Bilateral Renal Transplant, a Case Report and Review of the Literature. AB - In recent years, more women are undergoing renal transplantation as a treatment for end-stage renal disease. Women with kidney transplants are prone to certain gynecologic issues which might necessitate hysterectomy. Laparoscopic hysterectomy can safely be performed in patients with prior unilateral or bilateral renal transplantation. Laparoscopy offers magnification of anatomy, decreased wound-related problems, and continuation of immunosuppression therapy. We present a case report and review of the literature for total laparoscopic hysterectomy and bilateral salpingectomy for a patient with prior bilateral renal transplant. PMID- 29791698 TI - Stryker Orthopaedic Modeling and Analytics (SOMA): A Review. AB - Due to the differences in bone morphology between demographics such as age, gender, body mass index, and ethnicity, the development of orthopaedic implants requires a large number of anatomical data from various patient populations. In an effort to assess these demographic variations, Stryker Orthopaedic Modeling and Analytics (SOMA) has been developed. SOMA is a suite of tools which utilizes a comprehensive database of computed tomography scans (CT-scans), plus associated three-dimensional (3D) bone models, allowing the user to assess population differences in bone morphology, bone density, and implant fit for the purposes of research and development. Several additional software tools are currently in development to further analyze bone density and have the potential to enhance component fit. These tools, in combination with the database, have been previously utilized for development of many implant designs and techniques in hip and knee arthroplasty, as well as in trauma surgery. PMID- 29791699 TI - A Comparative Effectiveness Study for Non-Operative Treatment Methods for Knee Osteoarthritis. AB - A number of non-operative treatment options are commonly prescribed for patients presenting with degenerative osteoarthritis of the knee, where surgery is not yet recommended. However, there is a paucity of studies evaluating the comparative effectiveness of these treatment options to best inform both patients and providers. This study examined the comparative effectiveness of a home exercise program versus bracing or a combination of the two (brace-only, exercise-only, and brace and exercise cohorts) on the following: 1) objective functional measures (quadriceps muscle strength, Self-Paced Walk Test [SPWT], and Timed "Up & Go" [TUG] Test); 2) subjective functional measures (Lower Extremity Function Scale [LEFS] and Health Survey [VR-12] outcomes); 3) pain using Visual Analog Scale [VAS-10]; 4) patient metrics (patient treatment preference, perceptions, and compliance); and 5) progression to total knee arthroplasty (TKA) over a 12 week period. Subjects exhibited significant improvements from baseline on all measures regardless of group assignment; however, the only significant difference between groups was the larger improvement in pain scores between the brace-only and the exercise-only cohorts (p = 0.022). The brace-only regimen may be more efficacious; however, larger studies are needed to confirm this. These findings suggest that patients who are provided with either treatment option may be able to achieve a better quality of life and return to activity that may delay an elective joint arthroplasty surgery. PMID- 29791700 TI - Closing the Gap: Novel Abdominal Wound Closure Techniques. AB - Traditionally, surgical procedures within the realm of both general and gynecological surgery employ the use of staples and interrupted sutures that run continuously with knot tying or subcuticular sutures to ensure closure of large wound incisions, subcuticular incisions, and fascial repair. However, these methods may not always be cosmetically favorable and, thus, result in an unpleasant outcome for the patient, adding to their surgery-related stress. It is, therefore, imperative that surgeons and gynecologists are aware of alternative methods of wound closure that are not only cosmetically favorable, but also ensure rapid wound recovery and infection control. Two such products available include DERMABOND? PRINEO? Skin Closure System (Ethicon Inc., Somerville New Jersey) and STRATAFIX? Symmetric PDS? Plus Knotless Tissue Control Device (Ethicon Inc., Somerville New Jersey). The DERMABOND? PRINEO? Skin Closure System is a topical mesh and skin adhesive that creates a strong polymeric bond across wound edges. This permits natural healing to occur, but with a synthetic flexible microbial barrier providing in vitro protection against organisms. The STRATAFIX? Symmetric PDS? Plus, on the other hand, is a knotless tissue control device that permits soft tissue approximation in appropriate situations where such absorbable sutures are permitted. This can be used for large fascial closure as well as on the skin. The purpose of this article is to review and share our experience with two alternative methods of wound closure (one for fascia and one for skin) with a review of their composition and benefits and to illustrate their common applications in gynecologic or general surgery when laparotomy is necessary. PMID- 29791701 TI - Microbial Load of Trocars: Potential Source of Contamination and Surgical Site Infection. AB - Surgical site infection (SSI) is a common complication that is associated with delayed recovery, prolonged length of hospital stay, exorbitant cost, and mortality. The present prospective longitudinal study aimed to evaluate the relationships between the microbial load of trocars used in laparoscopic gynecological surgery, microbiota in surgical sites, and SSI. The final sample consisted of 24 patients, including 68 swab samples and 48 trocars. Microorganisms were recovered in 100.0% of the swabs collected from the umbilicus and vaginal fornix and in 58.3% (14/24) of the swabs collected from skin at the left McBurney's point. Most of the samples collected from trocars (87.5%) did not exhibit bacterial growth, suggesting proper disinfection. In addition, antisepsis was effective for decolonization of the skin to create an aseptic surgical field. PMID- 29791702 TI - All-Inside Technique for ACL-Reconstruction using a FlipCutter(r) and the TightRope(r) System. AB - There have been many innovations in the field of ACL-reconstruction over the years, including the FlipCutter(r) and TightRope(r) system (both from Arthrex Inc.). The FlipCutter(r) is a combined guide pin and reamer that allows minimally invasive socket-creation from the inside out, especially in difficult-to-reach areas. The TightRope(r) is a further development of the well-known Endobutton? (Smith & Nephew plc) that consists of a four-point knotless locking system. Its main advantage is its adjustability, which makes it possible to fill the entire bone socket with the graft without any empty space. The all-inside technique using a FlipCutter(r) and TightRope(r) offers several advantages: 1. No additional accessory portals and no hyperflexion of the knee are necessary during creation of the femoral canal. Using the FlipCutter(r), which is a "retro drill," an outside-in technique is applied. This avoids the problems that arise when using the anteromedial portal for creation of the femoral canal. 2. The thickness of the femoral wall can be accurately measured before drilling. 3. There is no empty space in the femoral canal. 4. Only one tendon is needed. Usually only the semitendinosus tendon is used. 5. There is no need for a tibial canal through the cortex. The procedure starts with diagnostic knee arthroscopy to confirm the ACL tear and to address any possible additional meniscal or cartilaginous lesions. Graft harvest and preparation (usually only the semitendinosus tendon is needed) is then performed. Next, the knee is prepared by creation of a femoral canal: after the entry point of the femoral canal is localized, while viewing through the medial portal with the knee held at 90 degrees of flexion, the femoral canal is created using the appropriate femoral guide and a FlipCutter(r). The tibial canal is then created using the tibial guide and a FlipCutter(r). Finally, the graft is passed through the medial portal to the femoral socket and stabilized with the TightRope(r). The tibial end is passed through the tibial canal and stabilized with a TightRope(r) ABS Button. In summary, this all inside technique for ACL- Reconstruction using FlipCutter(r) and TightRope(r) offers several advantages over traditional techniques, including no need for hyperflexion or an additional accessory medial portal while creating the femoral socket, accurate measurement of the whole thickness of the femoral condyle before drilling, the possibility of minor changes according to the desired femoral canal length, the ability to achieve no empty space in the femoral canal between the graft and bony canal, and the need for only one tendon (semitendinosus). Additionally, with this technique, the surgeon can easily place isometric sockets in the femur and tibia. PMID- 29791703 TI - Biological Intercalary Reconstruction with Bone Grafts After Joint-Sparing Resection of the Lower Limb: Is this an Effective and Durable Solution for Joint Preservation? AB - Due to advances in neoadjuvant therapies and preoperative imaging modalities, joint-sparing resections have become appealing in bone tumor surgery. However, the intercalary reconstruction of metadiaphyseal bone defects of the femur and the tibia after juxta-articular tumor resection remains challenging. Both biological and prosthetic reconstructions have been used for joint-sparing resections, but little is known about the long-term outcome of these procedures. The authors reviewed a consecutive series of 64 patients treated with joint sparing intercalary resection and reconstruction with bone grafts. Inclusion criteria were an osteotomy line within 5 cm from the knee and ankle joint surface and an osteotomy line proximal to 1 cm below the lesser trochanter at the hip level. Intra-epiphyseal resection was performed in 25 patients (39%)and intercalary resection was performed in 39 (61%). Reconstruction included 49 allograft + vascularized fibular graft (VFG), 10 allografts, and 5 VFG + structural allogenic grafts. At a mean follow-up of 117 months (range 12-305), 51 patients (80%) were continuously disease-free, and 6 showed no evidence of disease after treatment of local recurrence or metastatic lesion. One patient was alive with lung metastases at 26 months of follow-up and six patients died of disease. In the entire series of 64 patients, 26 had a non-oncological complication that required surgical revision (40.6%). Overall survival (OS) of reconstruction was 92% at 5 years and 90% at 10 and 15 years. Limb salvage survival (LSS) was 94% at 5, 10 and 15 years. Twenty-two fractures occurred in 17 patients (26.5%). There were a total of nine non-unions (14%). Six patients (9.3%) presented early wound dehiscence (average 1.8 months, range 0-6). A deep infection occurred in 3 cases (4.7 %). In 12 patients treated with VGF reconstruction (12/54:22%), a donor-site complication was observed. The overall Musculoskeletal Tumor Society (MSTS) functional score in 54 evaluable patients, who were alive with reconstruction in situ, was 27 points (range 18-30). Biologic intercalary reconstructions with bone grafts resulted in effective joint-sparing resections of the lower limb, allowing joint preservation in all but one case who required a total knee replacement for varus osteoarthritis. Despite the high rate of complications requiring surgical revision, at 15 years, overall survival of the reconstruction was 90% and limb salvage survival was 94%. In our experience, revision-free survival was better with VFG reconstruction than with allograft alone and the combination of VFG and allogenic graft seems to favor spontaneous fracture-healing and to decrease the non-union rate. PMID- 29791704 TI - Use of Neuromuscular Electrical Stimulation During Physical Therapy May Reduce the Incidence of Arthrofibrosis After Total Knee Arthroplasty. AB - INTRODUCTION: Arthrofibrosis remains a major complication following total knee arthroplasty (TKA) that negatively impacts patient outcomes and exhausts healthcare resources. The use of neuromuscular electrical stimulation (NMES) has demonstrated the ability to facilitate quadriceps muscle recovery and reduce pain. Therefore, the purpose of this study was to compare TKA patients who received physical therapy (PT) and adjuvant NMES therapy versus physical therapy alone in terms of: 1) rates of manipulation under anesthesia (MUA) to treat arthrofibrosis; and 2) post-therapy range of motion (ROM). MATERIALS AND METHODS: This was a retrospective review of TKA patients from multiple institutions who underwent physical therapy versus physical therapy and adjuvant NMES therapy following primary TKA. A total of 206 patients were reviewed in the two cohorts that either received PT alone (n=86) or PT and adjuvant NMES therapy (n=120). Data regarding the requirement of MUA postoperatively for treatment of arthrofibrosis were collected for every patient. Additionally, pre- and post therapy knee ROM data was also collected. Outcomes in both cohorts were then compared and analyzed. RESULTS: Lower rates of arthrofibrosis requiring MUA were recorded in patients who used NMES therapy and PT when compared to PT alone (7.5% vs. 19.8%; p=0.009). Log regression analysis revealed lower odds of needing MUA in patients who utilized NMES therapy in adjunct with PT (odds ratio [OR]=0.36; 95% CI: 0.115 to 0.875; p=0.023). Patients who received the NMES therapy were shown to have a statistically greater mean improvement in ROM when compared to those patients who did not receive NMES (+2.63, p=0.04). Log regression analysis also demonstrated that post-PT ROM decreased the odds of receiving MUA with a larger ROM (OR=92; 95% CI: 0.824 to 0.9855; p<0.001). CONCLUSION: This study demonstrated that the use of NMES during PT may reduce the incidence of arthrofibrosis and improve patient ROM. Prospective, randomized controlled, and larger-scale studies are needed to validate these results. Nevertheless, this novel report demonstrated the positive outcomes for a new application of the NMES therapy. PMID- 29791705 TI - Is There a Role for VATS Sleeve Lobectomy in Lung Cancer? AB - Lung cancer is the second most commonly diagnosed cancer and continues to be the leading cause of death for both men and women, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Once a lung mass is visualized on imaging, accurate staging is required for determination of treatment options and, when possible, surgical resection is recommended as it has been proven to have the best survival rates versus non-surgical treatment. If a patient has advanced or metastatic disease, therapeutic options include chemotherapy and radiation, while immunotherapy and specific agents that target tumor mutations are only recommended for appropriate candidates. Additionally, surgical options differ based on whether the tumor is peripherally or centrally located in the lung parenchyma. This article will review relevant literature concerning current surgical techniques for resection of centrally located NSCLC using thoracotomy and will emphasize the benefits and challenges of a video assisted thoracic surgery (VATS) approach. PMID- 29791706 TI - Use of a NobleStitch? EL Device for PFO Closure. AB - Cryptogenic stroke is the final diagnosis in almost 40% of ischemic acute cerebrovascular events. There is currently no definitive clinical evidence that percutaneous closure of patent foramen ovale (PFO) can prevent the recurrence of stroke or transient ischemic attack (TIA). Identification of the causes of neurologic ischemic syndromes is essential for any strategy intended to prevent the catastrophic consequences of cerebral infarction. Since the initial reports of an unexpectedly high prevalence of PFO in younger patients with cryptogenic stroke in 1988, there has been growing interest and experience in diagnosing and treating these patients, both medically and/or with percutaneous closure, in particular for the potential to eliminate paradoxical embolism via PFO, which is a likely mechanism for stroke in these patients. Selection of the appropriate occluder device is of paramount importance for the success of the procedure. While devices like the Amplatzer? PFO Occluder (St. Jude Medical), which, based on the extended follow-up of the RESPECT Trial, was approved by the U.S. Food and Drug Administration last year for recurrent stroke prevention, have become generally accepted as being better than medical therapy for patients needing treatment, concerns remain regarding device- and procedure-related complications. NobleStitch? EL is a novel device that offers a simple non-prosthetic implant method of PFO closure without the inherent risks seen with septal occluders: no risk of device embolization, device thrombosis or late erosion, and probably no risk of arrhythmia. Futhermore, there is no material that would hinder future access to the left atrium and no requirement for anti-coagulation. PMID- 29791707 TI - Evaluation of the Safety and Efficacy of a Novel Radiofrequency Device for Vaginal Treatment. AB - INTRODUCTION: Vaginal laxity and atrophy are caused mainly by aging and vaginal childbirth, which lead to a loss of strength and flexibility within the vaginal wall. As a result, women may experience vaginal, pelvic, sexual and urinary symptoms that significantly affect their quality of life. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a novel radiofrequency (RF) device for internal and external vaginal treatment. METHODS: Thirty women who had been diagnosed with symptoms of vaginal laxity and pelvic relaxation received a single treatment that consisted of continuous RF in the internal genitalia and continuous RF followed by fractional RF in the external vulva. Three different treatment conditions were examined. The results were evaluated by questionnaires and photos at two months post-treatment compared to baseline. RESULTS: For all parameters that were scored in the questionnaires, including vaginal symptoms, sexual matters, quality of life, pelvic floor impact and Stress Urinary Incontinence, significant improvements were found at a 2-month follow-up, compared to baseline (p<0.001). No significant or unexpected adverse events were noted. CONCLUSIONS: The present results suggest that this novel RF-based device with continuous and fractional RF technologies is useful, safe and effective for treating vaginal relaxation and atrophy symptoms. PMID- 29791708 TI - D3 Extended Mesenterectomy in Right Colectomy for Cancer: A Cadaver Simulation Model. AB - BACKGROUND: D3 extended mesenterectomy (D3EM) for right colon cancer has received increased attention owing to suggested improvement of oncological outcomes. The aim of this study was to evaluate the proficiency-based progression of content valid metrics in a cadaveric model for right colectomy with D3EM. MATERIALS AND METHODS: Three expert surgeons were enrolled. Surgeon one performed the procedure robotically and surgeons two and three performed open D3EM. Proficiency-based progression was recorded for eight content-valid outcomes. The superior mesenteric vein (SMV) and artery were cannulated by independent observers to evaluate vascular tears. The specimens were analyzed for lymph node harvest by a pathologist blinded to surgical access and to the surgeon. RESULTS: Operating times did not differ among surgeons (50.2, 32.4 and 43.7 min). SMV tears occurred in procedures A and B only. There was no significant progression in lymph node harvest for D2 (p=0.913) and D3EM (p=0.264). CONCLUSIONS: Cadaveric training in D3EM was associated with progression in avoidance of vascular tears with no significant changes in operating time and lymph node harvest. PMID- 29791709 TI - Sub-Trochanteric Hip Fracture Following Core Decompression for Osteonecrosis in a Patient with a Pre-Existing Contralateral Occult Femoral Neck Fracture. AB - We present a unique case of a 62-year-old patient with bilateral osteonecrosis of the femoral heads secondary to corticosteroid use. She presented with an occult right femoral neck fracture and was treated with percutaneous pinning of the right femoral neck and a left-sided percutaneous drilling. Despite apparent appropriate technique, the patient sustained a left sub-trochanteric hip fracture while shifting in bed in the postoperative care unit and was taken back for cephalo-medullary nail fixation. Femoral head osteonecrosis may be an under reported risk factor for development of pathological neck fractures. We present an overview of this topic along with suggestions for joint preservation treatment of similar patients at higher risk for perioperative fracture. PMID- 29791711 TI - Percutaneous Edge-to-Edge Transcatheter Mitral Valve Repair: Current Indications and Future Perspectives. AB - Mitral regurgitation (MR) is the most prevalent valvular heart disease (VHD) and represents an important cause of heart failure. Medical therapy has a limited role in improving symptoms and does not hinder the progression of valvular disease. Surgery is the treatment of choice for severe symptomatic MR; valve repair is currently the preferred surgical approach because it reduces peri operative mortality and ensures a good medium- to long-term survival outcome. Nevertheless, a non-negligible proportion of patients with indications for surgical correction are considered to be at prohibitive perioperative risk, mainly because of old age and multiple comorbidities. The introduction of percutaneous interventions to clinical practice has changed the natural history of this population. Percutaneous edge-to-edge transcatheter mitral valve repair (Mitraclip(r), Abbott Vascular, Menlo Park, CA) is a state-of-the-art therapy for approaching MR in patients with a high surgical risk. Despite having been only recently introduced, this transvenous transfemoral percutaneous intervention has already been performed in more than 40,000 subjects worldwide, with reassuring post-operative results in terms of safety, feasibility, mortality and morbidity. Since Mitraclip(r) is considered to be minimally invasive, it is currently indicated in "frail" patients with severe comorbidities. We provide a critical review of the literature to clarify current indications, procedural details, patient selection criteria, and future perspectives for this innovative technique. PMID- 29791710 TI - Postoperative Pain and Analgesia: Is There a Genetic Basis to the Opioid Crisis? AB - BACKGROUND: Multiple factors have been implicated in determining why certain patients have increased postoperative pain, with the potential to develop chronic pain. The purpose of this study was to: 1) identify and describe genes that affect postoperative pain perception and control; 2) address modifiable risk factors that result in epigenetic altered responses to pain; and 3) characterize differences in pain sensitivity and thresholds between opioid-naive and opioid dependent patients. MATERIALS AND METHODS: Three electronic databases were used to conduct the literature search: Pubmed, EBSCO host, and SCOPUS. A total of 372 abstracts were reviewed, of which 46 studies were deemed relevant and are included in this review. RESULTS: Specific gene alterations that were shown to affect postoperative pain control included single nucleotide polymorphisms in the mu, kappa, and delta opioid receptors, ion channel genes, cytotoxic T-cells, glutamate receptors and cytokine genes, among others. Alcoholism, obesity, and smoking were all linked with genetic polymorphisms that altered pain sensitivity. Opioid abuse was found to be associated with a poorer response to analgesics postoperatively, as well as a risk for prescription overdose. CONCLUSION: Although pain perception has multiple complex influences, the greatest variability seen in response to opioids among postoperative patients known to date can be traced to genetic differences in opioid metabolism. Further study is needed to determine the clinical significance of these genetic associations. PMID- 29791712 TI - Surgical Management After Hysteroscopic Sterilization: Minimally Invasive Approach Incorporating Intraoperative Fluoroscopy for Symptomatic Patients with >2 Essure(r) Devices. AB - OBJECTIVE: To describe a non-hysterectomy surgical technique for symptomatic patients with >2 Essure(r) (Bayer Healthcare, Whippany, New Jersey) devices. DESIGN: Patients (n=4) presented with sharp pelvic pain, irregular vaginal bleeding, dyspareunia, weight gain, hair loss, fatigue, and/or diffuse skin rash, all of which were absent before undergoing hysteroscopic sterilization (HS). Hysterosalpingogram obtained before surgical excision of contraceptive tubal implants confirmed more than two Essure(r) devices in all patients. Except for HS associated complaints, all patients were in otherwise good general health and none had any history of prior pelvic pathology. Hysteroscopy was followed by 5mm triple-port laparoscopic cornual dissection, modified partial bilateral salpingectomy, and foreign body removal under fluoroscopy and/or radiographic guidance. RESULTS: In this group, mean+/-SD patient age was 41+/-8yrs and interval between HS and device removal was 6.4+/-2.7yrs. At the conclusion of each case (mean+/-SD operative time=179+/-11min), imaging studies were reviewed by an attending radiologist and verified no retained metal in the abdomen. Conversion to laparotomy, hysterectomy, or blood transfusion was unnecessary for any patients, and all were discharged home within three hours. Their postoperative course continues to be satisfactory. CONCLUSION: Patients with more than two Essure(r) devices comprise an unusual group with a complex pelvic foreign body presentation. This is the first report on surgical management for such patients, underscoring the importance of localizing these contraceptive devices with careful imaging before, during, and after surgery. Moreover, hysterectomy is not absolutely mandatory in this setting and intraoperative fluoroscopy/radiography can facilitate complete, safe removal of all implants on an out-patient basis. Creation of ICD-10 modifiers for various post-HS complaints would allow for improved surveillance of the Essure(r) phenomenon. PMID- 29791713 TI - The Transradial Approach for Lower Extremity Vascular Intervention. AB - Simultaneous technological advancements in both imaging as well as devices have resulted in an expansion of endovascular options for vascular access. In particular, radial access has traditionally been more favored for coronary interventions; its use in the aortoiliac and lower extremity vasculature has been constrained by the length of devices and the size of sheaths required. However, with increasing catheter shaft lengths, in addition to new thin-walled sheaths allowing for downsizing, the ability to perform transradial interventions on infrainguinal and infrageniculate vessels has been more readily facilitated. In this review, we analyze the potential for transradial therapies in the treatment of peripheral arterial disease (PAD). PMID- 29791714 TI - The Problem of Seroma After Ventral Hernia Repair. AB - Seroma is a common postoperative finding after ventral hernia repair with an incidence of 20%. Often, it can be managed conservatively, but in the case of persistent or chronic seroma, reinterventions may be required. Closed drain suction has been the mainstay of seroma management for the last 40 years. Other alternative technologies have been evaluated to improve outcomes with mixed results. Because seroma is common, it is often an accepted outcome. Patient morbidity and costs to the healthcare system are underestimated, which begs for a re-evaluation of the current state of seroma management that is nearly a half century old. PMID- 29791715 TI - Genome skimming provides new insight into the relationships in Ludwigia section Macrocarpon, a polyploid complex. AB - PREMISE OF THE STUDY: Interpreting relationships within groups containing polyploids, which are frequent in angiosperms, can be greatly assisted by genomic techniques. In this study, we used a genome-skimming approach to investigate the evolutionary relationships and origins of polyploids in the monophyletic group, Ludwigia section Macrocarpon (Onagraceae), which includes diploid, tetraploid, and hexaploid taxa. METHODS: We sampled all known taxa and ploidy levels in the section and conducted shotgun sequencing. We assembled plastomes, mitochondrial sequences, and completed nuclear ribosomal regions, reconstructed phylogenies, and conducted comparative genomic analyses for plastomes to gain insights into the relationships among studied taxa. KEY RESULTS: Within the section, results showed that the South American diploid taxa L. bonariensis and L. lagunae were closely related. We reported the first chromosome count (2n = 4* = 32) for L. neograndiflora, which is closely related to the two South American diploid taxa, although its exact origin remains unclear. The samples of the widespread, polyploid taxon L. octovalvis do not form a monophyletic group. Both tetraploid and hexaploid L. octovalvis lineages have originated more than once. At least one tetraploid in the L. octovalvis lineage may have been involved in the origins of hexaploids. One or more extinct/unsampled intermediate tetraploids in the L. octovalvis lineages had also likely been involved in the origins of hexaploids. CONCLUSIONS: Genome skimming provided important insights into the complex evolutionary relationships within sect. Macrocarpon, but additional sampling and data from single-copy nuclear regions are necessary to further elucidate the origins of the polyploids in this section. PMID- 29791716 TI - A traditional Chinese remedy points to a natural skin habitat: indirubin (indigo naturalis) for psoriasis and the Malassezia metabolome. PMID- 29791717 TI - Termination of pregnancy following a prenatal diagnosis of Down syndrome: A qualitative study of the decision-making process of pregnant couples. AB - INTRODUCTION: In Denmark, first trimester screening has a very high uptake (>90%). If Down syndrome is diagnosed, termination rates are high (>95%). The aim of this study was to investigate the timing of the decision to terminate pregnancy following a diagnosis of Down syndrome and the factors influencing this decision. MATERIAL AND METHODS: Semi-structured, qualitative interview study with 21 couples who had received a prenatal diagnosis of Down syndrome and decided to terminate the pregnancy. Participants were recruited from obstetric departments between February 2016 and July 2017. Data were analyzed using thematic analysis. RESULTS: Five themes were identified: "initial decision-making", "consolidating the decision", "reasons and concerns shaping the termination of pregnancy decision", "the right decision is also burdensome", and "perceived influences in decision-making". For most couples, the initial decision to terminate pregnancy was made before or during the diagnostic process, but it was re-addressed and consolidated following the actual diagnosis. Imagining a family future with a severely affected Down syndrome child was the main factor influencing the termination of pregnancy decision. The decision was articulated as "right" but also as existentially burdensome for some, due to fear of regret and concern about ending a potential life. The decision to terminate pregnancy was considered a private matter between the couple, but was refined through interactions with clinicians and social networks. CONCLUSION: All couples made an initial decision prior to receiving the Down syndrome diagnosis. Knowledge of the couple's initial decision may facilitate patient-centered communication during and after the diagnostic process. Couples may benefit from counseling to deal with grief and existential concerns. PMID- 29791719 TI - Molecular and morphological diversity of Trebouxia microalgae in sphaerothallioid Circinaria spp. lichens1. AB - Three vagrant (Circinaria hispida, Circinaria gyrosa, and Circinaria sp. 'paramerae') and one crustose (semi-vagrant, Circinaria sp. 'oromediterranea') lichens growing in very continental areas in the Iberian Peninsula were selected to study the phycobiont diversity. Mycobiont identification was checked using nrITS DNA barcoding: Circinaria sp. 'oromediterranea' and Circinaria sp. 'paramerae' formed a new clade. Phycobiont diversity was analyzed in 50 thalli of Circinaria spp. using nrITS DNA and LSU rDNA, with microalgae coexistence being found in all the species analyzed by Sanger sequencing. The survey of phycobiont diversity showed up to four different Trebouxia spp. as the primary phycobiont in 20 thalli of C. hispida, in comparison with the remaining Circinaria spp., where only one Trebouxia was the primary microalga. In lichen species showing coexistence, some complementary approaches are needed (454 pyrosequencing and/or ultrastructural analyses). Five specimens were selected for high-throughput screening (HTS) analyses: 22 Trebouxia OTUs were detected, 10 of them not previously known. TEM analyses showed three different cell morphotypes (Trebouxia sp. OTU A12, OTU S51, and T. cretacea) whose ultrastructure is described here in detail for the first time. HTS revealed a different microalgae pool in each species studied, and we cannot assume a specific pattern between these pools and the ecological and/or morphological characteristics. The mechanisms involved in the selection of the primary phycobiont and the other microalgae by the mycobiont are unknown, and require complex experimental designs. The systematics of the genus Circinaria is not yet well resolved, and more analyses are needed to establish a precise delimitation of the species. PMID- 29791718 TI - Alopecia areata: a review of disease pathogenesis. AB - BACKGROUND: Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation. Objectives In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion. METHODS: We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis. RESULTS: The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune-cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon-gamma, interleukin-15, MICA and NKG2D, have been identified as contributing to the autoimmune process. CONCLUSIONS: Alopecia areata remains incurable, although it has been studied for years. Available treatment options at best are beneficial for milder cases, and the rate of relapse is high. Understanding the exact mechanisms of hair loss in alopecia areata is therefore of utmost importance to help identify potential therapeutic targets. PMID- 29791720 TI - C4 photosynthesis and transition of Kranz anatomy in cotyledons and leaves of Tetraena simplex. AB - PREMISE OF THE STUDY: Tetraena simplex is an independently evolved C4 species in the Zygophylloideae (Zygophyllaceae) and a characteristic forb of saline flats in hot and sandy desert habitats. During early ontogeny, the species had a morphological shift from planar cotyledons (dorsiventral symmetry) to terete, succulent leaves (radial symmetry). We tested whether this shift had a corresponding change in internal Kranz anatomy and tissue patterning. METHODS: For a comprehensive characterization of C4 photosynthesis across early ontogeny in T. simplex, structural and ultrastructural anatomical properties and localization patterns, activities, and immunoblotting of key C4 photosynthetic enzymes were compared in mesophyll and bundle sheath tissues in cotyledons and leaves. KEY RESULTS: Cotyledons and leaves possessed different types of Kranz anatomy (atriplicoid type and a "Tetraena" variant of the kochioid type, respectively), reflecting the change in leaf morphology. In bundle sheath cells, key differences in ultrastructural features included increased organelle numbers and chloroplast thylakoid stacking. C4 enzymes had strict tissue-specific localization patterns within bundle sheath and mesophyll cells in both cotyledons and leaves. The decarboxylase NAD-ME maintained the highest activity, increasing from cotyledons to leaves. This classified T. simplex as fully C4 across ontogeny and a strictly NAD-ME biochemical subtype. CONCLUSIONS: Tetraena simplex cotyledons and leaves showed differences in Kranz type, with associated progression in ultrastructural features, and differing activities/expression levels of C4 enzymes. Furthermore, leaves characterized a new "Tetraena" variation of the kochioid Kranz anatomy. PMID- 29791721 TI - Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naive patients from the French National Health Insurance database (SNIIRAM). AB - BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naive patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naive (mean age 48.6 years; males 57.3%, mean follow-up 3.6 years). The mean +/- SD length of follow-up for biologic-naive patients was 3.6 +/- 2.4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61.9% for the first, 33.3% for the third and 22.6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics. PMID- 29791722 TI - Does Lindioil (indirubin) treatment affect the composition of Malassezia species on psoriatic skin? PMID- 29791723 TI - Incomplete functional and morphological recovery after acute and acute recurrent pancreatitis in children. AB - BACKGROUND AND AIM: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. METHODS: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (MUg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DIo ) (mmol/L) (beta-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. RESULTS: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 +/- 150.94 (AP), 135.70 +/- 103.80 (ARP), 46.56 +/- 30.20 (CP), and 240.00 +/- 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DIo (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively. CONCLUSION: There was high frequency of biochemical evidence of exocrine insufficiency. beta-Cell function (DIo ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging. PMID- 29791724 TI - Resolving ambiguities in SUDEP classification. AB - OBJECTIVE: To examine the consistency of applying the Nashef et al (2012) criteria to classify sudden unexpected death in epilepsy (SUDEP). METHODS: We reviewed cases from the North American SUDEP Registry (n = 250) and Medical Examiner Offices (n = 1301: 698 Maryland, 457 New York City, 146 San Diego). Two epileptologists with expertise in SUDEP and epilepsy-related mortality independently reviewed medical records, scene investigation, autopsy, and toxicology and assigned a SUDEP class. RESULTS: Major areas of disagreement arose between adjudicators concerned differentiating (1) Definite SUDEP Plus Comorbidity from Possible SUDEP and (2) Resuscitated (Near) SUDEP from SUDEP. In many cases, distinguishing between contributing and competing causes of death when trying to classify Definite SUDEP Plus Comorbidity versus Possible SUDEP is ambiguous and relies on judgement. Similarly, determining if an intervention was lifesaving or not (Resuscitated SUDEP or Not SUDEP), or if resuscitation merely delayed SUDEP (Resuscitated SUDEP or SUDEP) is often a judgement call and can differ between experienced adjudicators. Given these persisting ambiguities, we propose more explicit criteria for distinguishing these categories. SIGNIFICANCE: Accurate and consistent classification of cause of death among individuals with epilepsy remains a dire public health concern. SUDEP is likely underestimated in national health statistics. Greater standardization of criteria among epilepsy researchers, medical examiners, and epidemiologists to determine cause and classify death will lead to more accurate tracking of SUDEP and other epilepsy related mortalities. PMID- 29791725 TI - Measuring the implementation of early childhood development programs. AB - In this paper we describe ways to measure variables of interest when evaluating the implementation of a program to improve early childhood development (ECD). The variables apply to programs delivered to parents in group sessions and home or clinic visits, as well as in early group care for children. Measurements for four categories of variables are included: training and assessment of delivery agents and supervisors; program features such as quality of delivery, reach, and dosage; recipients' acceptance and enactment; and stakeholders' engagement. Quantitative and qualitative methods are described, along with when measures might be taken throughout the processes of planning, preparing, and implementing. A few standard measures are available, along with others that researchers can select and modify according to their goals. Descriptions of measures include who might collect the information, from whom, and when, along with how information might be analyzed and findings used. By converging on a set of common methods to measure implementation variables, investigators can work toward improving programs, identifying gaps that impede the scalability and sustainability of programs, and, over time, ascertain program features that lead to successful outcomes. PMID- 29791726 TI - Building capacity in health and education systems to deliver interventions that strengthen early child development. AB - Building capacity within health and education systems of low- and middle-income countries in order to deliver high-quality early childhood services requires coordinated efforts across sectors, effective governance, sufficient funding, an adequate workforce, reliable data systems, and continuous monitoring, evaluation, and improvement cycles; it also requires partnerships with the private sector, communities, and parents. In addition, building capacity requires leadership, innovation of strategies to fit into existing structures, evidence-based intervention models, and effective partnerships that help make interventions more culturally relevant, help finance them, and help create institutional long-term support and sustainability for them. In this article, we focus on identifying eight critical aspects of enabling systemic support for early childhood services. Every action that strengthens these critical aspects should be seen as necessary, but insufficient, steps toward a national strong governance structure for delivering a locally relevant and comprehensive early child development program that promotes children's developmental potentials. PMID- 29791727 TI - Measuring the cost of investing in early childhood interventions and applications of a standardized costing tool. AB - In this paper we analyze the need for consistent and accurate cost data on early childhood development (ECD) interventions as a basis for increasing and improving the effectiveness of current spending on ECD. We establish the key components necessary in a costing model and present a new standardized costing tool intended for use across a broad range of stakeholders and contexts. Learnings from piloting the tool in Bangladesh, Malawi, Mali, Mexico, and Mozambique are shared. Providing a standardized methodology for costing ECD is an important contribution to the field and has the potential to improve both the volume and effectiveness of ECD financing. PMID- 29791728 TI - State of the science on implementation research in early child development and future directions. AB - We summarize the state of the field of implementation research and practice for early child development and propose recommendations. First, conclusions are drawn regarding what is generally known about the implementation of early childhood development programs, based on papers and discussions leading to a published series on the topic. Second, recommendations for short-term activities emphasize the use of newly published guidelines for reporting data collection methods and results for implementation processes; knowledge of the guidelines and a menu of measures allows for planning ahead. Additional recommendations include careful documentation of early-stage implementation, such as adapting a program to a different context and assessing feasibility, as well as the process of sustaining and scaling up a program. Using existing implementation information by building on and improving past programs and translating them into policy are recommended. Longer term goals are to identify implementation characteristics of effective programs and determinants of these characteristics. PMID- 29791729 TI - Implementation of Reach Up early childhood parenting program: acceptability, appropriateness, and feasibility in Brazil and Zimbabwe. AB - Young children need nurturing care, which includes responsive caregiver-child interactions and opportunities to learn. However, there are few extant large scale programs that build parents' abilities to provide this. We have developed an early childhood parenting training package, called Reach Up, with the aim of providing an evidence-based, adaptable program that is feasible for low-resource settings. Implementation of Reach Up was evaluated in Brazil and Zimbabwe to inform modifications needed and identify challenges that implementers and delivery agents encountered. Interview guides were developed to collect information on the program's appropriateness, acceptability, and feasibility from mothers, home visitors, and supervisors. Information on adaptation was obtained from country program leads and Reach Up team logs, as well as quality of visits from observations conducted by supervisors. The program was well accepted by mothers and visitors, who perceived benefits for the children; training was viewed as appropriate, and visitors felt well-prepared to conduct visits. A need for expansion of supervisor training was identified and the program was feasible to implement, although challenges were identified, including staff turnover; implementation was less feasible for staff with other work commitments (in Brazil). However, most aspects of visit quality were high. We conclude that the Reach Up program can expand capacity for parenting programs in low- and middle income countries. PMID- 29791730 TI - Integration of parenting and nutrition interventions in a community health program in Pakistan: an implementation evaluation. AB - Policy and program implementers require evidence on whether integrated psychosocial stimulation and nutrition interventions can be effectively delivered at-scale, how, and at what cost? To address some of these issues, a comprehensive evaluation of implementation was designed for a trial in Pakistan that integrated psychosocial stimulation and nutrition interventions in a community health service. The first objective was to describe, analyze, and assess the quality and accuracy of the implementation of the interventions. The second objective was to identify barriers and facilitators for uptake of interventions. A mixed-methods evaluation of implementation processes was conducted. Interventions were accepted by the community and health providers and there was evidence for behavior change uptake of the care for early childhood care recommendations. The new interventions did not dilute delivery of routine services. However, fidelity and quality required supportive supervision and active use of monitoring data, which would require attention in scale-up. PMID- 29791731 TI - Translation of evidence to practice to promote early childhood development programs. AB - The 2018 special issue of Annals of the New York Academy of Sciences on implementation research and practice for early childhood development brings together emerging evidence on implementing effective nurturing care programs, addressing issues of quality and scale. Translating evidence to practice requires addressing the barriers perceived by policy makers, which have been highlighted in the published literature. Here, I describe how UNICEF and other global partners are addressing these barriers. PMID- 29791733 TI - Implementation research for early childhood development programming in humanitarian contexts. AB - Young children living in conditions of war, disaster, and displacement are at high risk for developmental difficulties that can follow them throughout their lives. While there is robust evidence supporting the need for early childhood development (ECD) in humanitarian settings, implementation of ECD programming remains sparse, largely due to the lack of evidence of how and why these programs can improve outcomes in humanitarian settings. In order to build the evidence base for ECD in humanitarian settings, we review the current state of implementation research for ECD programming (targeting children 0-8) in humanitarian settings, through a literature review and a series of key informant interviews. Drawing from existing frameworks of implementation research and the findings from our analysis, we present a framework for ECD implementation research in humanitarian settings and propose an agenda for future research. PMID- 29791732 TI - Care for Child Development in rural Malawi: a model feasibility and pilot study. AB - Evidence demonstrates that encouraging stimulation, early communication, and nutrition improves child development. Detailed feasibility studies in real-world situations in Africa are limited. We piloted Care for Child Development through six health surveillance assistants (HSAs) in group and individual sessions with 60 caregivers and children <2 years and assessed recruitment, frequency, timings, and quality of intervention. We collected baseline/endline anthropometric, child development (MDAT), maternal stress (SRQ), and family care indicators (FCIs) data and determined acceptability through 20 interviews with caregivers and HSAs. HSAs could only provide coverage on 14.2% of eligible children in their areas; 86% of group sessions and a mean of 3.6/12 individual sessions offered to mothers were completed. Pre- and post-assessment of children demonstrated significant changes in MDAT language and social Z-scores and FCIs. Caregivers perceived sessions as beneficial and HSAs good leaders but that they could be provided through other mechanisms. Integrated Care for Child Development programs for 0-2 years old are readily accepted in Malawi, but they are not feasible to conduct universally through HSAs due to limited coverage; other models need to be considered. PMID- 29791734 TI - Implementing aeioTU: quality improvement alongside an efficacy study-learning while growing. AB - Effectiveness trials of increasing childhood development interventions across low and middle-income countries have shown significant variability. The strength and consistency of benefits for children are dependent on program quality, and this requires paying attention to program implementation. In this paper, we summarize findings on program quality and teacher practices and perceptions for the aeioTU program, a center-based Reggio-inspired program in Colombia, now serving more than 13,000 children. The research found engaged, committed staff who valued the emergent approach and understood the children as requiring opportunities to express themselves, being the source for the curriculum, and having relationships with the materials around them. Although the average classroom quality was low in 2011, it increased significantly by 2014, particularly in the language and reasoning and interactions items. Indicator-level analyses showed that higher order interactions and language processes were observed in a large proportion of classrooms by 2014. Teachers' self-reports on the environment and their teaching and learning showed high levels of quality by 2013. These findings illustrate the significance of process data for program improvement, especially when a program is young. Program quality can be raised after teachers improve their skills, have experience enacting a curriculum, and after training has been strengthened in response to information, while simultaneously scaling up the program. PMID- 29791735 TI - Practical considerations for transitioning early childhood interventions to scale: lessons from the Saving Brains portfolio. AB - Small pilot studies of young children have frequently shown promise, but very few have been successfully scaled to the regional or national levels. How can we ensure that these promising approaches move from a suite of pilots to full-scale implementation that can deliver sustainable impact for hundreds of millions of children? To elucidate concrete lessons learned and suggestions on accelerating the transition to impact at scale, we reviewed the Saving Brains portfolio to better understand three points: (1) the extent to which useful signals of impact could be extracted from data at the seed phase, (2) the ways in which innovators (project leaders) were approaching human resource challenges critical for scaling, and (3) the multisector diversity of the portfolio and the way innovators entered partnerships. The findings suggest key considerations for transitioning early childhood development interventions to scale and sustainability: strong entrepreneurial leadership, rigorous measurement and active use of data in support of adaptive learning, and champions acting at subnational levels. Together, these can enable flexible, iterative learning that can make the scaling process an opportunity to increase the level of benefit each child receives from an intervention. PMID- 29791736 TI - Program to Improve Private Early Education (PIPE): a case study of a systems approach for scaling quality early education solutions. AB - FSG is a mission-driven nonprofit organization supporting leaders in creating large-scale, lasting social change. A survey conducted by FSG in 2015 across 4407 low-income families in urban India showed that 95% of them send their children to preschools, a majority of choosing affordable private preschools (APSs), as parents perceive the quality of government schools to be poor. Parents use and value rote-based methods (e.g., reciting poems) to assess their children's learning in school; however, these methods fail to measure conceptual understanding. The APS system delivers on these rote approaches using inappropriate pedagogy, leading to poor learning outcomes. Affordable high quality activity-based preschool solutions exist and could be brought to the APS to significantly improve the classroom environment and learning outcomes. This requires changing mindsets of all actors-solution provider companies, APS owners, APS teachers, and low-income parents. We present FSG's approach to shaping demand for quality preschool services and to improve learning outcomes in urban Indian APSs through the implementation of the pilot Program to Improve Private Early Education (PIPE). PMID- 29791737 TI - Reporting guidelines for implementation research on nurturing care interventions designed to promote early childhood development. AB - Meta-analyses of interventions such as parenting, stimulation, and early childhood education have reported consistent medium-to-high effect sizes on early childhood development (ECD) and early learning outcomes. However, few effective interventions promoting ECD have achieved scale. In order to increase the access to effective or high-quality services, greater focus on implementation research of interventions promoting ECD is necessary. In this paper, we describe the development of reporting guidelines for implementation research of nurturing care interventions designed to promote ECD following an expert consensus-building process. The goal of these guidelines is to support a transparent and standard reporting of implementation evidence on nurturing care interventions designed to promote early childhood development. PMID- 29791738 TI - Designing, testing, and implementing a sustainable nurse home visiting program: right@home. AB - Nurse home visiting (NHV) offers a potential platform to both address the factors that limit access to services for families experiencing adversity and provide effective interventions. Currently, the ability to examine program implementation is hampered by a lack of detailed description of actual, rather than expected, program development and delivery in published studies. Home visiting implementation remains a black box in relation to quality and sustainability. However, previous literature would suggest that efforts to both report and improve program implementation are vital for NHV to have population impact and policy sustainability. In this paper, we provide a case study of the design, testing, and implementation of the right@home program, an Australian NHV program and randomized controlled trial. We address existing gaps related to implementation of NHV programs by describing the processes used to develop the program to be trialed, summarizing its effectiveness, and detailing the quality processes and implementation evaluation. The weight of our evidence suggests that NHV can be a powerful and sustainable platform for addressing inequitable outcomes, particularly when the program focuses on parent engagement and partnership, delivers evidence-based strategies shown to improve outcomes, includes fidelity monitoring, and is adapted to and embedded within existing service delivery systems. PMID- 29791739 TI - What implementation evidence matters: scaling-up nurturing interventions that promote early childhood development. AB - Research in early childhood development (ECD) has established the need for scaling-up multisectoral interventions for nurturing care to promote ECD, for improved socioeconomic outcomes for sustainable societies. However, key elements and processes for implementation and scale-up of such interventions are not well understood. This special series on implementation research and practice for ECD brings together evidence to inform effectiveness, quality, and scale in nurturing care programs; identifies knowledge gaps; and proposes further directions for research and practice. This paper frames the dimensions and components fundamental to the understanding of implementation processes for nurturing care interventions, factors for improving implementation of interventions, and strategies to scale by embedding interventions in delivery systems. We discuss emerging issues in implementation research for ECD, including (1) the role of context in adaptation and implementation, (2) standardized reporting of implementation research, (3) the importance of feasibility studies to inform scale-up and capacity building, (4) fidelity and program quality improvement, and (5) intervention integration into existing systems. Effective implementation of nurturing care interventions is at the heart of achieving positive developmental outcomes for young children. It is pivotal to adapt and implement these interventions based on evidence for high impact, especially in low-resource settings. PMID- 29791740 TI - The Irie Classroom Toolbox: developing a violence prevention, preschool teacher training program using evidence, theory, and practice. AB - In this paper, I describe the development of the Irie Classroom Toolbox, a school based violence prevention, teacher training program for use with children aged 3 6 years. In-depth interviews were conducted with Jamaican preschool teachers, who had participated in a trial of a classroom behavior management program, at posttest (n = 35) and 5 years later (n = 20). An on-going process evaluation was also conducted. Teachers' preferred behavior management strategies and training methods were documented, and enablers and barriers to implementation were identified. Teachers were most likely to adopt strategies that they liked, found easy to use, and were effective. These included paying attention to positive behavior and explicitly teaching children the expected behavior. Teachers preferred active, hands-on training strategies based on social-cognitive theories. Enablers to intervention implementation included positive teacher facilitator relationships, choice, collaborative problem solving, teachers recognizing benefits of the intervention, group support, and provision of materials. Barriers to intervention implementation were also identified. These data were integrated with behavior change theory (i.e., the behavior change wheel and theoretical domains framework) to develop an intervention grounded in common core elements of evidence-based programs while also utilizing teachers' perspectives. The resulting program is a low cost, adaptable intervention that should be suitable for training preschool teachers in other low-resource settings. PMID- 29791741 TI - Diffusing and scaling evidence-based interventions: eight lessons for early child development from the implementation of perinatal home visiting in South Africa. AB - Most low- and middle-income countries lack resources with which to implement public health programs. As such, there is a necessity to facilitate programing that judiciously makes use of what resources there are. However, despite evidence for the efficacy of many interventions, translating these into real-world effectiveness, and then into scalability, is complex and has often been neglected. We draw on a case study of Philani+ (a maternal and child health intervention implemented in South Africa) to distil eight features of health programing that aid intervention effectiveness. We argue that implementation science should turn its attention to the human resource "process" features of interventions. We describe the importance of staff selection (rigorous selection and hiring procedures); training (developing a set of common core pragmatic problem-solving skills); monitoring (feedback about quality); community and institutional support (rapport with intervention communities); the importance of stable leadership (consistent leadership focusing on how to optimize the potential of staff); the importance of implementing with sustainable, long-term change in mind; and, finally, we describe how cultivating consistency within an organization requires disciplined action and disciplined focus on the organization's vision. PMID- 29791742 TI - What policymakers need from implementation evaluations of early childhood development programs. AB - As early childhood interventions move from small- to large-scale programs, the partnerships among researchers, policymakers, communication experts, practitioners, and local communities become increasingly critical for successful implementation. The results from evaluations of programs need to guide policymakers so that they can make informed administrative and fiscal decisions. This commentary makes five recommendations for researchers to consider when designing early childhood programs for scale. PMID- 29791743 TI - A network for early childhood development. AB - Political action and investment are critical to meet the development needs of vulnerable young children today. Early childhood development (ECD) has become a global priority: an ECD target and other ECD-related targets are included in the sustainable development goals, over 75 countries have officially adopted multisectoral ECD policy instruments, and ECD is a programmatic focus in major global institutions (including UNICEF, UNESCO, the WHO, and the World Bank). However, lack of clear and strong ownership of and champions for ECD, operational and communication siloes of constituent sectors that constitute ECD, political pressures for investment in other arenas, and low international investment in ECD inhibit making a compelling and cohesive investment case for ECD. This commentary explores how a global ECD network can facilitate systematic alignment and action across sectors to support country systems, strengthen political will, and increase investment to deliver results for young children's development. The ECD Action Network is in formation and offers an opportunity for the field to share knowledge among countries and sectors, identify pathways for sectoral coordination and collaboration, and undertake advocacy to generate the scale of political and financial support necessary to ensure that every child receives the nurturing care he/she needs. PMID- 29791745 TI - Nursing as a pathway to women's empowerment and intergenerational mobility. AB - AIM AND OBJECTIVE: To assess the impact of nursing education on the intergenerational mobility of graduates of nursing upskilling programmes. BACKGROUND: Challenges for low- and middle-income countries include poverty and limited access to health, education and social services compounded by workforce shortages, inequality and female disempowerment. Little is known about the impact of nursing education on women's empowerment and intergenerational mobility in such settings. DESIGN: A cross-sectional study using data collected through an online alumni survey. METHODS: Data were collected March to May 2016 using an online questionnaire, as part of a larger nursing programme alumni survey. Intergenerational mobility was assessed by comparing the respondents' educational qualification with their fathers' and mothers' education levels. Descriptive statistics were analysed using frequencies and percentages. Associations between parental and respondents' education levels were assessed using chi-square tests. RESULTS: Out of 446 female respondents who completed the survey, 379 and 366 indicated their fathers' and mothers' education level, respectively. A third of the respondents' mothers had no formal schooling; lower levels of parental education are significantly associated with increase in respondents age (p < 0.001) and associated shift from Uganda to Kenya and Tanzania (p < 0.001). Respondents had a marked upward intergenerational education mobility with 76% (278/366) and 59% (223/379) of them achieving a qualification two levels above their mothers and fathers, respectively. Tanzanian respondents had significantly higher rates of upward mobility than Kenyan and Ugandan respondents. CONCLUSIONS: Nursing education positively impacted gender, economic factors and health outcomes. Further research is needed to confirm the "triple impact" of nursing education on improving health, gender equality and economic growth in low- and middle-income countries. RELEVANCE TO CLINICAL PRACTICE: Nurses are frontline providers of healthcare services. Provision of high-quality nursing upgrade programmes enhances nursing leadership ability, with aligned improvements in health outcomes while supporting gender empowerment and intergenerational mobility. PMID- 29791744 TI - PF-06526290 can both enhance and inhibit conduction through voltage-gated sodium channels. AB - BACKGROUND AND PURPOSE: Pharmacological agents that either inhibit or enhance flux of ions through voltage-gated sodium (Nav ) channels may provide opportunities for treatment of human health disorders. During studies to characterize agents that modulate Nav 1.3 function, we identified a compound that appears to exhibit both enhancement and inhibition of sodium ion conduction that appeared to be dependent on the gating state that the channel was in. The objective of the current study was to determine if these different modulatory effects are mediated by the same or distinct interactions with the channel. EXPERIMENTAL APPROACH: Electrophysiology and site-directed mutation were used to investigate the effects of PF-06526290 on Nav channel function. KEY RESULTS: PF 06526290 greatly slows inactivation of Nav channels in a subtype-independent manner. However, upon prolonged depolarization to induce inactivation, PF 06526290 becomes a Nav subtype-selective inhibitor. Mutation of the domain 4 voltage sensor modulates inhibition of Nav 1.3 or Nav 1.7 channels by PF-06526290 but has no effect on PF-06526290 mediated slowing of inactivation. CONCLUSIONS AND IMPLICATIONS: These findings suggest that distinct interactions may underlie the two modes of Nav channel modulation by PF-06526290 and that a single compound can affect sodium channel function in several ways. PMID- 29791747 TI - Commentary on "The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal model of epilepsy". PMID- 29791748 TI - A bright forecast for autoregulation monitoring? PMID- 29791746 TI - Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus. AB - Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide (AgRP) and anorexigenic pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC), yet nicotine and other nAChR agonists decrease food intake in mice. Viral mediated knockdown of the beta4 nAChR subunit in all neuronal cell types in the ARC prevents the nicotinic agonist cytisine from decreasing food intake, but it is not known whether the beta4 subunit is selectively expressed in anorexigenic neurons or how other nAChR subtypes are distributed in this nucleus. Using translating ribosome affinity purification (TRAP) on ARC tissue from mice with ribosomes tagged in either AgRP or POMC cells, we examined nAChR subunit mRNA levels using real-time PCR. Both AgRP and POMC cells express a comparable panel of nAChR subunits with differences in alpha7 mRNA levels and a trend for difference in alpha4 levels, but no differences in beta4 expression. Immunoprecipitation of assembled nAChRs revealed that the beta4 subunit forms assembled channels with alpha3, beta2 and alpha4, but not other subunits found in the ARC. Finally, using cell type-selective, virally delivered small hairpin RNAs targeting either the beta4 or alpha7 subunit, we examined the contribution of each subunit in either AgRP or POMC cells to the behavioural response to nicotine, refining the understanding of nicotinic regulation of this feeding circuit. These experiments identify a more complex set of nAChRs expressed in ARC than in other hypothalamic regions. Thus, the ARC appears to be a particular target of nicotinic modulation. PMID- 29791750 TI - Tiled array-based sequencing identifies enrichment of loss-of-function variants in the highly homologous filaggrin gene in African-American children with severe atopic dermatitis. AB - Filaggrin (FLG) loss-of-function (LOF) variants are a major risk factor for the common inflammatory skin disease, atopic dermatitis (AD) and are often population specific. African-American (AA) children are disproportionately affected with AD, often later developing asthma and/or allergic rhinitis and comprise an atopy health disparity group for which the role of FLG LOF is not well known. Discovery of FLG LOF using exome sequencing is challenging given the known difficulties for accurate short-read alignment to FLG's high homology repeat variation. Here, we employed an array-based sequencing approach to tile across each FLG repeat and discover FLG LOF in a well-characterized cohort of AA children with moderate-to severe AD. Five FLG LOF were identified in 23% of our cohort. Two novel FLG LOF singletons, c.488delG and p.S3101*, were discovered as well as p.R501*, p.R826* and p.S3316* previously reported for AD. p.S3316* (rs149484917) is likely an African ancestral FLG LOF, reported in African individuals in ExAC (Exome Aggregation Consortium), Exome Variant Server (ESP), and 4 African 1000G population databases (ESN, MSL, ASW, and ACB). The proportion of FLG LOF (11.5%) among the total FLG alleles in our cohort was significantly higher in comparisons with FLG LOF reported for African individuals in ExAC (2.5%; P = 4.3 * 10-4 ) and ESP (1.7%; P = 3.5 * 10-5 ) suggesting a disease-enrichment effect for FLG LOF. Our results demonstrate the utility of array-based sequencing in discovering FLG LOF, including novel and population-specific, which are of higher prevalence in our AA severe AD group than previously reported. PMID- 29791749 TI - Reactivity of 3,3,3-Trifluoropropyne at Rhodium Complexes: Development of Hydroboration Reactions. AB - The rhodium compounds [Rh(C=CCF3 )(PEt3 )3 ] (2), fac-[RhH(C=CCF3 )2 (PEt3 )3 ] (3), and fac-[Rh{(E)-CH=CHCF3 }(C=CCF3 )2 (PEt3 )3 ] (4) were synthesized by reactions of the rhodium(I) complexes [Rh(H)(PEt3 )3 ] (1) and [Rh(Bpin)(PEt3 )3 ] (5, HBpin=pinacolborane) with the alkyne 3,3,3-trifluoropropyne. Reactivity studies of [Rh(C=CCF3 )(PEt3 )3 ] (2) were performed with CO and 13 CO to form [Rh(C=CCF3 )(CO)(PEt3 )3 ] (7) and subsequently trans-[Rh(C=CCF3 )(CO)(PEt3 )2 ] (8) as well as the labeled derivatives. Using 1-4 as catalysts, hydroboration reactions selectively afforded borylated building blocks. PMID- 29791751 TI - Reducing branched-chain amino acid intake to reverse metabolic complications in obesity and type 2 diabetes. PMID- 29791752 TI - Subcentimetre non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). PMID- 29791753 TI - Double Jeopardy - Missed care for the vulnerable in community settings. PMID- 29791755 TI - Commentary: 2017 clinical Epilepsia prize. PMID- 29791754 TI - ATP triggers a robust intracellular [Ca2+ ]-mediated signalling pathway in human synovial fibroblasts. AB - NEW FINDINGS: What is the central question of this study? What are the main [Ca2+ ]i signalling pathways activated by ATP in human synovial fibroblasts? What is the main finding and its importance? In human synovial fibroblasts ATP acts through a linked G-protein (Gq ) and phospholipase C signalling mechanism to produce IP3 , which then markedly enhances release of Ca2+ from the endoplasmic reticulum. These results provide new information for the detection of early pathophysiology of arthritis. ABSTRACT: In human articular joints, synovial fibroblasts (HSFs) have essential physiological functions that include synthesis and secretion of components of the extracellular matrix and essential articular joint lubricants, as well as release of paracrine substances such as ATP. Although the molecular and cellular processes that lead to a rheumatoid arthritis (RA) phenotype are not fully understood, HSF cells exhibit significant changes during this disease progression. The effects of ATP on HSFs were studied by monitoring changes in intracellular Ca2+ ([Ca2+ ]i ), and measuring electrophysiological properties. ATP application to HSF cell populations that had been enzymatically released from 2-D cell culture revealed that ATP (10-100 MUm), or its analogues UTP or ADP, consistently produced a large transient increase in [Ca2+ ]i . These changes (i) were initiated by activation of the P2 Y purinergic receptor family, (ii) required Gq -mediated signal transduction, (iii) did not involve a transmembrane Ca2+ influx, but instead (iv) arose almost entirely from activation of endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate (IP3 ) receptors that triggered Ca2+ release from the ER. Corresponding single cell electrophysiological studies revealed that these ATP effects (i) were insensitive to [Ca2+ ]o removal, (ii) involved an IP3 -mediated intracellular Ca2+ release process, and (iii) strongly turned on Ca2+ -activated K+ current(s) that significantly hyperpolarized these cells. Application of histamine produced very similar effects in these HSF cells. Since ATP is a known paracrine agonist and histamine is released early in the inflammatory response, these findings may contribute to identification of early steps/defects in the initiation and progression of RA. PMID- 29791756 TI - Interactions between insulin and diet on striatal dopamine uptake kinetics in rodent brain slices. AB - Diet influences dopamine transmission in motor- and reward-related basal ganglia circuitry. In part, this reflects diet-dependent regulation of circulating and brain insulin levels. Activation of striatal insulin receptors amplifies axonal dopamine release in brain slices, and regulates food preference in vivo. The effect of insulin on dopamine release is indirect, and requires striatal cholinergic interneurons that express insulin receptors. However, insulin also acts directly on dopamine axons to increase dopamine uptake by promoting dopamine transporter (DAT) surface expression, counteracting enhanced dopamine release. Here, we determined the functional consequences of acute insulin exposure and chronic diet-induced changes in insulin on DAT activity after evoked dopamine release in striatal slices from adult ad-libitum fed (AL) rats and mice, and food restricted (FR) or high-fat/high-sugar obesogenic (OB) diet rats. Uptake kinetics were assessed by fitting evoked dopamine transients to the Michaelis-Menten equation and extracting Cpeak and Vmax . Insulin (30 nm) increased both parameters in the caudate putamen and nucleus accumbens core of AL rats in an insulin receptor- and PI3-kinase-dependent manner. A pure effect of insulin on uptake was unmasked using mice lacking striatal acetylcholine, in which increased Vmax caused a decrease in Cpeak . Diet also influenced Vmax , which was lower in FR vs. AL. The effects of insulin on Cpeak and Vmax were amplified by FR but blunted by OB, consistent with opposite consequences of these diets on insulin levels and insulin receptor sensitivity. Overall, these data reveal acute and chronic effects of insulin and diet on dopamine release and uptake that will influence brain reward pathways. PMID- 29791757 TI - Organ donation after euthanasia, morally acceptable under strict procedural safeguards. AB - In this paper, we will present a case of organ donation after active euthanasia (ODE) in the Netherlands from a patient who had his life ended at his explicit and voluntary request. The form of ODE we describe here concerns patients who are not unconscious and on life support, but who are conscious and want to have their life ended because of their hopeless and unbearable suffering, for instance due to a terminal illness such as Amyotrophic Lateral Sclerosis (ALS) or Multiple Sclerosis (MS). This form of ODE is of course only possible in jurisdictions where euthanasia is allowed. In these jurisdictions, organ donation after euthanasia is an option that may be considered. We believe ODE is worthwhile to pursue, as it can strengthen patient autonomy, can give meaning to the inevitable death of the patient, and be an extra source of much needed donor organs. To ensure voluntariness of both euthanasia and organ donation and avoid conflict of interest by physicians, ODE does need strict procedural safeguards however. The most important safeguard is a strict separation between the 2 procedures. The paper discusses several ethical issues such as who should broach the subject of organ donation and who should perform the euthanasia, and how a conflict of interest can be avoided. PMID- 29791758 TI - Posttraumatic stress symptomatology following exposure to perceived traumatic perinatal events within the midwifery profession: The impact of trait emotional intelligence. AB - AIMS: To explore factors associated with, and predictors of, posttraumatic stress symptoms in midwives. To explore factors associated with, and potential moderating effects of, trait emotional intelligence. Secondary analysis explored predictors of resilience. BACKGROUND: Midwives may experience vicarious trauma responses due to exposure to certain perinatal events in their professional lives. This may have adverse psychological outcomes for midwives, and women and children in their care. DESIGN: A cross-sectional, online and paper survey of midwives in the United Kingdom was conducted. METHODS: Between February and October 2016, 113 midwives who met inclusion criteria provided demographic information, and completed scales measuring posttraumatic stress symptoms, trait emotional intelligence, empathy, resilience, social support, and attitudes towards emotional expression. RESULTS: Higher resilience and trait emotional intelligence scores were associated with reduced posttraumatic stress symptoms. Higher empathy, perceived social support, and resilience were associated with higher trait emotional intelligence. Lower resilience significantly predicted posttraumatic stress symptoms. Trait emotional intelligence did not moderate relationships between resilience and posttraumatic stress symptoms, but may protect against posttraumatic stress symptoms in midwives with higher empathy. Higher trait emotional intelligence, and lower empathy and need for support, significantly predicted resilience. Notably, when trait emotional intelligence was higher, the negative relationship between empathy and resilience was reduced. CONCLUSION: Approximately one-fifth of midwives were experiencing posttraumatic stress symptoms at clinically significant levels. Trait emotional intelligence may protect against posttraumatic stress symptoms by supporting resilience, while enabling midwives to remain empathic. The negative correlation between resilience and empathy needs careful consideration by policy makers. PMID- 29791759 TI - CTNNAL1 inhibits ozone-induced epithelial-mesenchymal transition in human bronchial epithelial cells. AB - NEW FINDINGS: What is the central question of this study? What is the effect of catenin alpha-like 1 (CTNNAL1), an asthma-related epithelial adhesion molecule that plays a vital role in airway epithelial wound repair, on airway epithelial mesenchymal transition? What is the main finding and its importance? CTNNAL1 inhibits ozone-induced airway epithelial-mesenchymal transition features, mediated by repressing the expression of Twist1 mRNA and reducing TGF-beta1 levels. These findings contribute to our understanding of the pathology of airway EMT and may indicate a possible therapeutic target for airway remodelling in bronchial asthma. ABSTRACT: Epithelial-mesenchymal transition (EMT), a crucial event occurring during epithelial and mesenchymal repair, was reported to be a possible mechanism for airway remodelling. Our previous work showed that the expression of catenin alpha-like 1 (CTNNAL1) was down-regulated in the bronchial epithelial cells of asthmatic models and played a vital role in airway epithelial wound repair. The aim of this study was to investigate the effect of CTNNAL1 on airway EMT. Overexpression or silencing of CTNNAL1 in human bronchial epithelial cells was induced by stable transfection. CTNNAL1 was silenced in primary mouse airway epithelial cells with an effective siRNA vector. Cells were stressed by ozone for 4 days at 30 min day-1 to induce EMT. EMT features, changes in the function of co-cultured lung fibroblasts, changes in the expression of the transcriptional repressors Snail/Slug and Twist1/Twist2 and changes in the secretion of transforming growth factor beta1 (TGF-beta1) were assayed in different cell lines with or without ozone exposure. Both ozone exposure and silencing of CTNNAL1 induced EMT features in airway epithelial cells. Functional changes in lung fibroblasts increased after co-culture with (ozone-stressed) CTNNAL1-silenced cells. Snail and Twist1 expression increased, and the level of TGF-beta1 was enhanced. Conversely, CTNNAL1 overexpression reversed EMT features, repressed mRNA levels of Twist1 and reduced the secretion of TGF-beta1, both alone and in combination with ozone exposure. Our results indicate that ozone exposure induces airway EMT and that CTNNAL1 inhibits ozone-induced airway EMT. CTNNAL1 may play a role in airway EMT by repressing the expression of Twist1 mRNA and reducing the level of TGF-beta1. PMID- 29791761 TI - Nerve action potential amplitude, a robust marker of diabetic peripheral neuropathy. PMID- 29791762 TI - Ethical dilemmas in nursing: An integrative review. AB - AIMS: To identify themes and gaps in the literature to stimulate researchers to develop strategies to guide decision-making among clinical nurses faced with ethical dilemmas. BACKGROUND: The concept of ethical dilemmas has been well explored in nursing because of the frequency of ethical dilemmas in practice and the toll these dilemmas can take on nurses. Although ethical dilemmas are prevalent in nursing practice, frequently leading to moral distress, there is little guidance in the literature to help nurses resolve them. DESIGN: This study is an integrative review of published research from 2000 to 2017. METHODS: The keywords ethics, ethical dilemmas and nurs* were searched in CINAHL, PubMed, OVID and SCOPUS. Exclusion criteria were sources not available in English, not in acute care, and without an available abstract. Seventy-two studies were screened; 35 were retained. Garrard's matrix was utilised to analyse and synthesise the studies. RESULTS: Ethical dilemmas arose from end-of-life issues, conflict with physicians or families, patient privacy concerns and organisational constraints. Differences were found in study location, and yet international research confirms that ethical dilemmas are universally prevalent and must be addressed globally to protect patients and nurses. CONCLUSIONS: This review offers an analysis of the available evidence regarding ethical dilemmas in acute care, identifying themes, limitations and gaps in the literature. The gaps in quantitative intervention work, US paucity of research, and lack of comparisons across practice settings/nursing roles must be addressed. Further exploration is warranted in the relationship between ethical dilemmas and moral distress, the significance patient physical appearance plays on nurse determination of futility, and strategies for pain management and honesty. RELEVANCE TO NURSING PRACTICE: Understanding and addressing gaps in research is essential to develop strategies to help nurses resolve ethical dilemmas and to avoid moral distress and burnout. PMID- 29791763 TI - Payments for ecosystem services in Mexico reduce forest fragmentation. AB - Forest fragmentation can lead to habitat reduction, edge increase, and exposure to disturbances. A key emerging policy to protect forests is payments for ecosystem services (PES), which offers compensation to landowners for environmental stewardship. Mexico was one of the first countries to implement a broad-scale PES program, enrolling over 2.3 Mha by 2010. However, Mexico's PES did not completely eliminate deforestation in enrolled parcels and could have increased incentives to hide deforestation in ways that increased fragmentation. We studied whether Mexican forests enrolled in the PES program had less forest fragmentation than those not enrolled, and whether the PES effects varied among forest types, among socioeconomic zones, or compared to the protected areas system. We analyzed forest cover maps from 2000 to 2012 to calculate forest fragmentation. We summarized fragmentation for different forest types and in four socioeconomic zones. We then used matching analysis to investigate the possible causal impacts of the PES on forests across Mexico and compared the effects of the PES program with that of protected areas. We found that the area covered by forest in Mexico decreased by 3.4% from 2000 to 2012, but there was 9.3% less forest core area. Change in forest cover was highest in the southern part of Mexico, and high-stature evergreen tropical forest lost the most core areas ( 17%), while oak forest lost the least (-2%). Our matching analysis found that the PES program reduced both forest cover loss and forest fragmentation. Low-PES areas increased twice as much of the number of forest patches, forest edge, forest islets, and largest area of forest lost compared to high-PES areas. Compared to the protected areas system in Mexico, high-PES areas performed similarly in preventing fragmentation, but not as well as biosphere reserve core zones. We conclude that the PES was successful in slowing forest fragmentation at the regional and country level. However, the program could be improved by targeting areas where forest changes are more frequent, especially in southern Mexico. Fragmentation analyses should be implemented in other areas to monitor the outcomes of protection programs such as REDD+ and PES. PMID- 29791760 TI - Neopterin/7,8-dihydroneopterin is elevated in Duchenne muscular dystrophy patients and protects mdx skeletal muscle function. AB - NEW FINDINGS: What is the central question of this study? We examined whether the macrophage-synthesized antioxidant 7,8-dihydroneopterin was elevated in Duchenne muscular dystrophy (DMD) patients. We then examined whether 7,8-dihydroneopterin could protect dystrophic skeletal mouse muscle from eccentric contraction-induced force loss and improve recovery. What is the main finding and its importance? Urinary neopterin/creatinine and 7,8-dihydroneopterin/creatinine were elevated in DMD patients. 7,8-Dihydroneopterin attenuated eccentric contraction-induced force loss of dystrophic skeletal mouse muscle and accelerated recovery of force. These results suggest that eccentric contraction-induced force loss is mediated, in part, by an oxidative component and provides a potential protective role for 7,8 dihydroneopterin in DMD. ABSTRACT: Macrophage infiltration is a hallmark of dystrophin-deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage-synthesized pterins, neopterin and 7,8-dihydroneopterin, compared with unaffected age-matched control subjects. Urinary neopterin/creatinine and 7,8 dihydroneopterin/creatinine were elevated in DMD patients, and 7,8 dihydroneopterin/creatinine was associated with patient age and ambulation. Urinary 7,8-dihydroneopterin corrected for specific gravity was also elevated in DMD patients. Given that 7,8-dihydroneopterin is an antioxidant, we then identified a potential role for 7,8-dihydroneopterin in disease pathology. We assessed whether 7,8-dihydroneopterin could: (i) protect against isometric force loss in wild-type skeletal muscle exposed to various pro-oxidants; and (ii) protect wild-type and mdx muscle from eccentric contraction-induced force loss, which has an oxidative component. Force loss was elicited in isolated extensor digitorum longus (EDL) muscles by 10 eccentric contractions, and recovery of force after the contractions was measured in the presence of exogenous 7,8 dihydroneopterin. 7,8-Dihydroneopterin attenuated isometric force loss by wild type EDL muscles when challenged by H2 O2 and HOCl, but exacerbated force loss when challenged by SIN-1 (NO* , O2* , ONOO- ). 7,8-Dihydroneopterin attenuated eccentric contraction-induced force loss in mdx muscle. Isometric force production by EDL muscles of mdx mice also recovered to a greater degree after eccentric contractions in the presence of 7,8-dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8-dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate that oxidative stress contributes to eccentric contraction-induced force loss in mdx skeletal muscle. PMID- 29791765 TI - Resources for work-related well-being: A qualitative study about healthcare employees' experiences of relationships at work. AB - AIMS AND OBJECTIVES: To explore municipal healthcare employees' experiences of relationships with care recipients and colleagues. The specific research questions were when do the relationships enhance well-being, and what prerequisites are needed for such relationships to occur? BACKGROUND: Employees in health and social care for older people often depict their work in negative terms, and they often take a high number of sick leaves. Despite the heavy workload, other employees express well-being at work and highlight social relationships as one reason for this. However, a greater understanding of how these relationships can act as resources for workplace well-being is needed. DESIGN: The design of the study was qualitative and exploratory. METHODS: Qualitative interview studies were conducted with 23 healthcare employees in municipal health care. Thematic analysis was used to analyse the data. RESULTS: Two themes were identified as resources for promoting relationships between employees and care recipients or colleagues: (a) Being personal-a close interpersonal relationship to a care recipient-and (b) Colleague belongingness-a sense of togetherness within the working group. Spending quality time together, providing long-term care and providing additional care were prerequisites for a close interpersonal relationship with care recipients. Trust, mutual responsibility and cooperation were prerequisites for a sense of togetherness within the working group. CONCLUSIONS: The findings provide an empirical base to raise awareness of relationships with care recipients and colleagues as health aspects. Relationships among employees in health care are vital resources that must be considered to create sustainable workplaces and consequently improve the quality of care. RELEVANCE TO CLINICAL PRACTICE: The results of this study advocate health promotion efforts based on interpersonal relationships at the workplace. Dialogues in the working groups, based on the employees' experiences of positive daily situations, may be a promoting method for the work-related well being of the employees. PMID- 29791766 TI - Protein Regulation by Intrinsically Disordered Regions: A Role for Subdomains in the IDR of the HIV-1 Rev Protein. AB - Intrinsically disordered regions (IDRs) in proteins are highly abundant, but they are still commonly viewed as long stretches of polar, solvent-accessible residues. Here we show that the disordered C-terminal domain (CTD) of HIV-1 Rev has two subregions that carry out two distinct complementary roles of regulating protein oligomerization and contributing to stability. We propose that this takes place through a delicate balance between charged and hydrophobic residues within the IDR. This means that mutations in this region, as well as the known mutations in the structured region of the protein, can affect protein function. We suggest that IDRs in proteins should be divided into subdomains similarly to structured regions, rather than being viewed as long flexible stretches. PMID- 29791767 TI - Increased body size along urbanization gradients at both community and intraspecific level in macro-moths. AB - Urbanization involves a cocktail of human-induced rapid environmental changes and is forecasted to gain further importance. Urban-heat-island effects result in increased metabolic costs expected to drive shifts towards smaller body sizes. However, urban environments are also characterized by strong habitat fragmentation, often selecting for dispersal phenotypes. Here, we investigate to what extent, and at which spatial scale(s), urbanization drives body size shifts in macro-moths-an insect group characterized by positive size-dispersal links-at both the community and intraspecific level. Using light and bait trapping as part of a replicated, spatially nested sampling design, we show that despite the observed urban warming of their woodland habitat, macro-moth communities display considerable increases in community-weighted mean body size because of stronger filtering against small species along urbanization gradients. Urbanization drives intraspecific shifts towards increased body size too, at least for a third of species analysed. These results indicate that urbanization drives shifts towards larger, and hence, more mobile species and individuals in order to mitigate low connectivity of ecological resources in urban settings. Macro-moths are a key group within terrestrial ecosystems, and since body size is central to species interactions, such urbanization-driven phenotypic change may impact urban ecosystem functioning, especially in terms of nocturnal pollination and food web dynamics. Although we show that urbanization's size-biased filtering happens simultaneously and coherently at both the inter- and intraspecific level, we demonstrate that the impact at the community level is most pronounced at the 800 m radius scale, whereas species-specific size increases happen at local and landscape scales (50-3,200 m radius), depending on the species. Hence, measures such as creating and improving urban green infrastructure-to mitigate the effects of urbanization on body size will have to be implemented at multiple spatial scales in order to be most effective. PMID- 29791764 TI - Synergy between peroxisome proliferator-activated receptor gamma agonist and radiotherapy in cancer. AB - Angiogenesis and inflammation are crucial processes through which the tumor microenvironment (TME) influences tumor progression. In this study, we showed that peroxisome proliferator-activated receptor gamma (PPARgamma) is not only expressed in CT26 and 4T1 tumor cell lines but also in cells of TME, including endothelial cells and tumor-associated macrophages (TAM). In addition, we showed that rosiglitazone may induce tumor vessel normalization and reduce TAM infiltration. Additionally, 4T1 and CT26 tumor-bearing mice treated with rosiglitazone in combination with radiotherapy showed a significant reduction in lesion size and lung metastasis. We reported that a single dose of 12 Gy irradiation strongly inhibits local tumor angiogenesis. Secretion of C-C motif chemokine ligand 2 (CCL2) in response to local irradiation facilitates the recruitment of migrating CD11b+ myeloid monocytes and TAM to irradiated sites that initiate vasculogenesis and enable tumor recurrence after radiotherapy. We found that rosiglitazone partially decreases CCL2 secretion by tumor cells and reduces the infiltration of CD11b+ myeloid monocytes and TAM to irradiated tumors, thereby delaying tumor regrowth after radiotherapy. Therefore, combination of the PPARgamma agonist rosiglitazone with radiotherapy enhances the effectiveness of radiotherapy to improve local tumor control, decrease distant metastasis risks and delay tumor recurrence. PMID- 29791768 TI - Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models. AB - Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with Toll like receptor (TLR)3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In the present study, 4 different ovalbumin (OVA)-expressing tumor cell lines were implanted into syngeneic mice and subjected to anti-tumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a TLR3-specific agonist that does not activate the mitochondrial antiviral-signaling protein (MAVS) pathway, and thus does not induce systemic inflammation. Dendritic cell priming and proliferative CTL were induced by ARNAX + OVA, but complete remission was achieved only in a PD-L1-low cell line of EG7. Addition of anti-PD-L1 antibody to the ARNAX + OVA therapy brought complete remission to another PD-L1-high subline of EG7. Tumor shrinkage but not remission was observed in MO5 in that regimen. We analyzed tumor cells and tumor-infiltrating immune cells to identify factors associated with successful ARNAX vaccine therapy. Tumors that responded to ARNAX therapy expressed high levels of MHC class I and low levels of PD-L1. The tumor infiltrating immune cells in ARNAX-susceptible tumors contained fewer immunosuppressive myeloid cells with low PD-L1 expression. Combination with anti PD-L1 antibody functioned not only within tumor sites but also within lymphoid tissues, augmenting the therapeutic efficacy of the ARNAX vaccine. Notably, ARNAX therapy induced memory CD8+ T cells and rejection of reimplanted tumors. Thus, ARNAX vaccine + anti-PD-L1 therapy enabled permanent remission against some tumors that stably present antigens. PMID- 29791769 TI - Bioprospecting from marine coastal sediments of Colombian Caribbean: screening and study of antimicrobial activity. AB - AIMS: To isolate micro-organisms associated with marine coastal sediments of Colombian Caribbean Sea and for evaluating its antimicrobial activity in order to identify the most active strains. METHODS AND RESULTS: One hundred and four strains were isolated from sediment samples of the Colombian Caribbean Sea. First at all, an antimicrobial activity screening was made using agar well diffusion method against the pathogens: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, Candida tropicalis and Pseudomonas aeruginosa. Seventeen strains showed strong antimicrobial activity and were identified as members of the Streptomyces, Micrococcus and Bacillus genera. Organic extracts were produced by liquid-liquid extraction and HPLC profiles of the most active extracts were obtained. Then, the antimicrobial activity of the extracts was evaluated with the broth microdilution test, finding antimicrobial activities superior to 90% against S. aureus MRSA and C. albicans. HPLC profiles indicated the presence of different antimicrobial compounds. CONCLUSION: This study demonstrates that the microorganisms isolated from the Colombian Caribbean Sea are possible sources of antimicrobial compounds against pathogenic strains. SIGNIFICANCE AND IMPACT OF STUDY: These results contribute to the knowledge of the biotechnological potential of the Colombian biodiversity for the development of pharmaceutical products that can counteract the increasing problem of pathogen resistance. PMID- 29791770 TI - Modelling of factors influencing the effect of osmotic solution on reduction of selected microorganisms. AB - AIMS: The goal of this research is to model the effects of two osmotic solutions factors on the reduction of selected microorganisms, and to assess the application in osmotic dehydration process of animal raw materials from the aspect of microbiological safety. METHODS AND RESULTS: Sugar beet molasses and aquatic osmotic solution were prepared and inoculated with Escherichia coli, Listeria monocytogenes and Salmonella spp. Varied factors of osmotic solutions were: time, temperature and concentration of osmotic solutions. Samples of osmotic solutions were subjected to standard and modified microbiological ISO methods. The result showed that increase in factors had a positive effect on the reduction of microbiological load, while the time of the process was the most influential technological parameter. Number of L. monocytogenes was reduced to <10 CFU per g at the end of the process in the highest concentration of sugar beet molasses at all process temperatures. CONCLUSIONS: Developed mathematical models of reduction ratios for tested microorganisms were statistically significant, allowing good prediction of reduction ratio values based on applied factors. SIGNIFICANCE AND IMPACT OF THE STUDY: Obtained levels of reduction of all tested microorganisms present good base for the production of safe osmotically dehydrated products of animal origin. PMID- 29791773 TI - Vaginal microbiome studies in pregnancy must also analyse host factors. PMID- 29791771 TI - Minimal Information About an Immuno-Peptidomics Experiment (MIAIPE). AB - Minimal information about an immuno-peptidomics experiment (MIAIPE) is an initiative of the members of the Human Immuno-Peptidome Project (HIPP), an international program organized by the Human Proteome Organization (HUPO). The aim of the MIAIPE guidelines is to deliver technical guidelines representing the minimal information required to sufficiently support the evaluation and interpretation of immunopeptidomics experiments. The MIAIPE document has been designed to report essential information about sample preparation, mass spectrometric measurement, and associated mass spectrometry (MS)-related bioinformatics aspects that are unique to immunopeptidomics and may not be covered by the general proteomics MIAPE (minimal information about a proteomics experiment) guidelines. PMID- 29791772 TI - Characterization, culture medium optimization and antioxidant activity of an endophytic vitexin-producing fungus Dichotomopilus funicola Y3 from pigeon pea [Cajanus cajan (L.) Millsp.]. AB - AIMS: The aim of this study was to characterize a fungal endophyte Y3 from pigeon pea (Cajanus cajan [L.] Millsp), as a novel producer of vitexin, and its culture medium optimization and antioxidant activity. METHODS AND RESULTS: The endophyte from the leaves of pigeon pea was identified as Dichotomopilus funicola by the morphological and molecular characteristics. The most important medium variables affecting vitexin production in liquid culture of D. funicola Y3 were screened by Plackett-Burman design, and three culture medium constituents (i.e. l phenylalanine, salicylic acid and CuSO4 .5H2 O) were identified to play significant roles in vitexin production. The most significant factors were further optimized using by central composite design with response surface methodology. The DPPH radical-scavenging assay indicated that fungal vitexin exhibited notable antioxidant activity with an EC50 value of 164 MUg l-1 . CONCLUSIONS: First, a novel endophyte vitexin-producing Dichotomopilus funicola Y3 was isolated from pigeon pea (Cajanus cajan[L.] Millsp.). The maximum vitexin yield was obtained as 78.86 mg l-1 under the optimum culture medium constituents: 0.06 g l-1 l-phenylalanine, 0.21 g l-1 salicylic acid, and 0.19 g l-1 CuSO4 .5H2 O in medium, which is 4.59-fold higher than that in the unoptimized medium. Also, fungal vitexin clearly demonstrated its antioxidant potential. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings provide an alternative source for large-scale production of vitexin by endophytic fungal fermentation and have a promising prospect in food and pharmaceutical industry. PMID- 29791774 TI - Serotonergic regulation of insulin secretion. AB - The exact physiological role for the monoamine serotonin (5-HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signalling network in islets involving 5-HT is being unravelled. With more than fourteen different 5-HT receptors expressed in human islets and receptor-independent mechanisms in insulin-producing beta-cells, our understanding of 5-HT's regulation of insulin secretion is increasing. It is now widely accepted that failure of the pancreatic beta-cell to release sufficient amounts of insulin is the main cause of type 2 diabetes (T2D), an ongoing global epidemic. In this context, 5-HT signalling may be of importance. In fact, 5-HT may serve an essential role in regulating the release of insulin and glucagon, the two main hormones that control glucose and lipid homoeostasis. In this review, we will discuss past and current understanding of 5-HT's role in the endocrine pancreas. PMID- 29791775 TI - Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. AB - OBJECTIVES: To explore differences in the vaginal microbiome between preterm and term deliveries. DESIGN: Nested case-control study in 3D cohort (design, develop, discover). SETTING: Quebec, Canada. SAMPLE: Ninety-four women with spontaneous preterm birth as cases [17 early (<34 weeks) and 77 late (34-36 weeks) preterm birth] and 356 women as controls with term delivery (>=37 weeks). METHODS: To assess the vaginal microbiome by sequencing the V4 region of the 16S ribosomal RNA (rRNA) gene in swabs self-collected during early pregnancy. MAIN OUTCOME MEASURES: Comparison of relative abundance of bacterial operational taxonomic units and oligotypes and identifying vaginal community state types (CSTs) in early or late spontaneous preterm and term deliveries. RESULTS: Lactobacillus gasseri/ Lactobacillus johnsonii (coefficient -5.36, 95% CI -8.07 to -2.65), Lactobacillus crispatus (99%)/ Lactobacillus acidophilus (99%) (-4.58, 95% CI 6.20 to -2.96), Lactobacillus iners (99%)/ Ralstonia solanacearum (99%) (-3.98, 95% CI -6.48 to -1.47) and Bifidobacterium longum/ Bifidobacterium breve (-8.84, 95% CI -12.96 to -4.73) were associated with decreased risk of early but not late preterm birth. Six vaginal CSTs were identified: four dominated by Lactobacillus; one with presence of bacterial vaginosis-associated bacteria (Gardnerella vaginalis, Atopobium vaginae and Veillonellaceae bacterium) (CST IV); and one with nondominance of Lactobacillus (CST VI). CST IV was associated with increased risk of early (4.22, 95% CI 1.24-24.85) but not late (1.63, 95% CI 0.68-5.04) preterm birth, compared with CST VI. CONCLUSIONS: Lactobacillus gasseri/L. johnsonii, L. crispatus/L. acidophilus, L. iners/R. solanacearum and B. longum/B. breve may be associated with decreased risk of early preterm birth. A bacterial vaginosis-related vaginal CST versus a CST nondominated by Lactobacillus may be associated with increased risk of early preterm birth. TWEETABLE ABSTRACT: Largest study of its kind finds certain species of vaginal Lactobacillus + Bifidobacterium may relate to lower risk of preterm birth. PMID- 29791776 TI - Polymorphism in disease-related apolipoprotein C-II amyloid fibrils: a structural model for rod-like fibrils. AB - Human apolipoprotein (apo) C-II is one of several plasma apolipoproteins that form amyloid deposits in vivo and is an independent risk factor for cardiovascular disease. Lipid-free apoC-II readily self-assembles into twisted ribbon amyloid fibrils but forms straight, rod-like amyloid fibrils in the presence of low concentrations of micellar phospholipids. Charge mutations exerted significantly different effects on rod-like fibril formation compared to their effects on twisted-ribbon fibril formation. For instance, the double mutant, K30D-D69K apoC-II, readily formed twisted-ribbon fibrils, while the rate of rod-like fibril formation in the presence of micellar phospholipid was negligible. Structural analysis of rod-like apoC-II fibrils, using hydrogen deuterium exchange and NMR analysis showed exchange protection consistent with a core cross-beta structure comprising the C-terminal 58-76 region. Molecular dynamics simulations of fibril arrangements for this region favoured a parallel cross-beta structure. X-ray fibre diffraction data for aligned rod-like fibrils showed a major meridional spacing at 4.6 A and equatorial spacings at 9.7, 23.8 and 46.6 A. The latter two equatorial spacings are not observed for aligned twisted-ribbon fibrils and are predicted for a model involving two cross-beta fibrils in an off-set antiparallel structure with four apoC-II units per rise of the beta-sheet. This model is consistent with the mutational effects on rod-like apoC-II fibril formation. The lipid-dependent polymorphisms exhibited by apoC-II fibrils could determine the properties of apoC-II in renal amyloid deposits and their potential role in the development of cardiovascular disease. PMID- 29791777 TI - Counting on Death - Quantitative aspects of Bcl-2 family regulation. AB - The Bcl-2 protein family members critically regulate mitochondrial outer membrane permeabilization (MOMP), a point-of-no-return in the intrinsic and extrinsic apoptosis pathways. The common view on qualitative interaction and activation patterns of the three subclasses, the BH3-only proteins, prosurvivals, and effectors, is static and currently being revolutionized by an emerging understanding of the complex dynamic equilibria that govern cellular fate. Recent experimental evidence on protein associations with the mitochondrial outer membrane, retrotranslocation to the cytosol, and differential binding affinities in aqueous and membranous environments instigate the development of a revised model of Bcl-2 family interplay. Likely, the dynamic processes and their respective timescales need to be taken into account to authentically understand and, by extension, to generate reliable predictions on cellular decision-making. Here, we review the quantitative aspects of Bcl-2 family-regulated MOMP. In particular, we discuss affinity binding constants of protein-protein associations and velocities of post-translational modifications, membrane (retro-) translocations, and effector oligomerization. Moreover, we provide insights into how these kinetic and network information enable systems biological approaches, further enhancing our understanding of the complex molecular mechanisms governing MOMP. PMID- 29791778 TI - Tailor-made robotic anterior resection and hysterectomy - a video vignette. PMID- 29791779 TI - A Recent Perspective on Noncovalently Formed Polymeric Hydrogels. AB - Chemically crosslinked covalent hydrogels form a permanent and often strong network, and have been extensively used so far in drug delivery and tissue engineering. However, it is more difficult to induce dynamic and highly tunable changes in these hydrogels. Noncovalently formed hydrogels show promise as inherently reversible systems with an ability to change in response to dynamic environments, and have garnered strong interest recently. In this Personal Account, we elucidate a few key attractive properties of noncovalent hydrogels and describe recent developments in hydrogels crosslinked using various different noncovalent interactions. These hydrogels offer huge control for modulating material properties and could be more relevant mimics for biological systems. PMID- 29791780 TI - Solid-State Electrolyte Anchored with a Carboxylated Azo Compound for All-Solid State Lithium Batteries. AB - Organic electrode materials are promising for green and sustainable lithium-ion batteries. However, the high solubility of organic materials in the liquid electrolyte results in the shuttle reaction and fast capacity decay. Herein, azo compounds are firstly applied in all-solid-state lithium batteries (ASSLB) to suppress the dissolution challenge. Due to the high compatibility of azobenzene (AB) based compounds to Li3 PS4 (LPS) solid electrolyte, the LPS solid electrolyte is used to prevent the dissolution and shuttle reaction of AB. To maintain the low interface resistance during the large volume change upon cycling, a carboxylate group is added into AB to provide 4-(phenylazo) benzoic acid lithium salt (PBALS), which could bond with LPS solid electrolyte via the ionic bonding between oxygen in PBALS and lithium ion in LPS. The ionic bonding between the active material and solid electrolyte stabilizes the contact interface and enables the stable cycle life of PBALS in ASSLB. PMID- 29791783 TI - In silico and Wet Bench Interactomics Sheds Light on the Similitudes and Differences between Human ROCO Proteins. AB - Defining a common and specific function for homologs of a novel protein family is not a trivial task. In their recent study, Tomkins and colleagues have addressed this challenge for the ROCO protein family by exploring interactomes of its four human members: MASL1, DAPK1, LRRK1, and LRRK2. ROCO proteins are characterized by a Ras-GTPase domain embedded in complex multidomain proteins and a functional descriptor for this protein family has been elusive despite accumulating research, particularly for LRRK2, a protein implicated in Parkinson's disease. Tomkins et al. have combined an in silico weighted literature mining approach with novel interactomics data obtained on protein chips for all four proteins under strictly comparable conditions. The combination of these approaches has allowed the prudent formulation of common functions for ROCO proteins, including their involvement in stress response and cell projection organization. In addition, the study also confirms functional specificity for the individual ROCOs with such functions as cell death and apoptosis assigned to DAPK1, cellular, and neuronal development associated with LRRK1 and intracellular transport and organization assigned to LRRK2. PMID- 29791781 TI - A dual role of miR-22 in rhabdomyolysis-induced acute kidney injury. AB - AIM: In acute kidney injury (AKI), regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia-inducible factor (HIF) is limited. Here, we studied miR-22, a potential HIF repressor, in normal kidneys, as well as in rhabdomyolysis-induced AKI, a condition where miR-22 is up regulated. METHODS: AKI in mice was provoked by IM injection of glycerol. Tissue homogenates were processed to determine the levels of candidate RNAs and proteins, as well as global gene expression profiles. Reporter assays quantified in vitro miR-22 activity and its modulation by mimic or inhibitor molecules, under normoxia or hypoxia (1% O2 ) respectively. In vivo, anti-miR-22 molecules were applied to normal mice or prior to induction of AKI. Renal outcome was assessed by measuring plasma creatinine, plasma urea and the levels of the injury markers Kim-1 and Ngal. RESULTS: Renal miR-22 is inducible by hypoxia and represses hypoxia-inducible factor (HIF). Specific inhibition of miR-22 regulates 1913 gene transcripts in kidneys controls and 3386 in AKI, many of which are involved in development or carcinogenesis. Specific inhibition of miR-22 up regulates tissue protective HIF target genes, yet renal function and injury markers are unchanged or worsened. CONCLUSIONS: miR-22 is a HIF repressor constitutively expressed in the adult kidney and up-regulated in AKI. Specific inhibition of miR-22 is efficient in vivo and profoundly affects renal gene expression in health and disease, including up-regulation of HIF. However, the net effect on rhabdomyolysis-induced AKI outcome is neutral or even negative. PMID- 29791784 TI - Chitosan Hydrogels and Bionanocomposites Formed through the Mineralization and Regulated Charging. AB - The account presents survey of our systematic studies on chitosan. Only this polysaccharide bears cationic charges, possesses antimicrobial activity and wound healing ability that make it highly appropriate for using in medicine, biomedical engineering, cosmetics, food, packaging. However, its application meets with severe limitation. Chitosan belongs to polysaccharides that do not jellify solutions. Main approaches are based on the chemical modifications and cross linking, but these treatments impairs therewith the biocompatibility and biological activity of chitosan. We have developed approaches in which monolithic hydrogels are fabricated via the mineralization of polysaccharide by method of green sol-gel chemistry and via the formation of polyelectrolyte complex with oppositely charged counterparts in the regime of its charging by means of regulated acidification. The latter approach was also extended for the preparation of chitosan bionanocomposites and films with nanoparticles. PMID- 29791782 TI - Obesity leads to impairments in the morphology and organization of human skeletal muscle lipid droplets and mitochondrial networks, which are resolved with gastric bypass surgery-induced improvements in insulin sensitivity. AB - AIMS: Skeletal muscle lipid stores and mitochondrial function have been appointed as key players in obesity-induced insulin resistance. However, there are conflicting reports in the literature based on in vitro quantitative measurements. Here, we test the hypothesis that it is not the quantity but the quality that matters. METHODS: This study combines quantitative and qualitative structural measurements of lipid stores and mitochondrial dynamics in skeletal muscle from lean subjects, and subjects with morbid obesity, with and without type 2 diabetes, before and after gastric bypass surgery. RESULTS: The structural organization of muscle mitochondrial networks in type II muscle fibres from subjects with morbid obesity is impaired. In addition, the amount of skeletal muscle perilipin 2 protein per intramyocellular lipid is reduced in subjects with morbid obesity, resulting in qualitative alterations in perilipin 2 coat around some lipid droplets. Gastric bypass surgery-induced weight loss and insulin resistance remission were associated with decreases in intramyocellular lipid stores and, qualitative improvements in lipid droplets' morphology, perilipin 2 coat and mitochondrial dynamics. CONCLUSION: Morbid obesity leads to severe qualitative alterations of both skeletal muscle lipid stores and mitochondrial networks. The degree of structural improvements after gastric bypass surgery was proportional to the improvements in whole body insulin sensitivity, suggesting an association between these events. PMID- 29791785 TI - Expressed exome capture sequencing: A method for cost-effective exome sequencing for all organisms. AB - Exome capture is an effective tool for surveying the genome for loci under selection. However, traditional methods require annotated genomic resources. Here, we present a method for creating cDNA probes from expressed mRNA, which are then used to enrich and capture genomic DNA for exon regions. This approach, called "EecSeq," eliminates the need for costly probe design and synthesis. We tested EecSeq in the eastern oyster, Crassostrea virginica, using a controlled exposure experiment. Four adult oysters were heat shocked at 36 degrees C for 1 hr along with four control oysters kept at 14 degrees C. Stranded mRNA libraries were prepared for two individuals from each treatment and pooled. Half of the combined library was used for probe synthesis, and half was sequenced to evaluate capture efficiency. Genomic DNA was extracted from all individuals, enriched via captured probes, and sequenced directly. We found that EecSeq had an average capture sensitivity of 86.8% across all known exons and had over 99.4% sensitivity for exons with detectable levels of expression in the mRNA library. For all mapped reads, over 47.9% mapped to exons and 37.0% mapped to expressed targets, which is similar to previously published exon capture studies. EecSeq displayed relatively even coverage within exons (i.e., minor "edge effects") and even coverage across exon GC content. We discovered 5,951 SNPs with a minimum average coverage of 80*, with 3,508 SNPs appearing in exonic regions. We show that EecSeq provides comparable, if not superior, specificity and capture efficiency compared to costly, traditional methods. PMID- 29791787 TI - DNA barcoding of microgastrine parasitoid wasps (Hymenoptera: Braconidae) using high-throughput methods more than doubles the number of species known for Australia. AB - The Microgastrinae are a hugely diverse subfamily of endoparasitoid wasps of lepidopteran caterpillars. They are important in agriculture as biological control agents and play a significant ecological role in the regulation of caterpillar populations. Whilst the group has been the focus of intensive rearing and DNA barcoding studies in the Northern Hemisphere, the Australian fauna has received little attention. In total, 99 species have been described from or have been introduced into Australia, but the real species diversity for the region is clearly much larger than this. In this study, museum ethanol samples and recent field collections were mined for hundreds of specimens of microgastrine wasps, which were then barcoded for the COI region, ITS2 ribosomal spacer and the wingless nuclear genes, using a pooled sequencing approach on an Illumina Miseq system. Full COI sequences were obtained for 525 individuals which, when combined with 162 publicly available sequences, represented 417 haplotypes, and a total of 236 species were delimited using a consensus approach. By more than doubling the number of known microgastrine wasp species in Australia, our study highlights the value of DNA barcoding in the context of employing high-throughput sequencing methods of bulk ethanol museum collections for biodiversity assessment. PMID- 29791786 TI - Matrine suppresses KRAS-driven pancreatic cancer growth by inhibiting autophagy mediated energy metabolism. AB - Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level. We also found that either pyruvate or alpha-ketoglutarate supplementation markedly rescues pancreatic cancer cell growth following matrine treatment. Inhibition of mitochondrial energy production results from matrine-mediated autophagy inhibition by impairing the function of lysosomal protease. Matrine-mediated autophagy inhibition requires stat3 downregulation. Furthermore, we found that the antitumor effect of matrine on pancreatic cancer growth depends on the mutation of the KRAS oncogene. Together, our data suggest that matrine can suppress the growth of KRAS-mutant pancreatic cancer by inhibiting autophagy mediated energy metabolism. PMID- 29791788 TI - Shift in skin microbiota of Western European women across aging. AB - AIMS: The objective of our study was to compare the microbiota diversity between two different age groups of Western European women. METHODS AND RESULTS: Skin swab samples were collected directly on the forehead of 34 healthy Western European women: 17 younger (21-31 years old) and 17 older individuals (54-69 years old). Bacterial communities were evaluated using the 16S rRNA gene sequencing. Data revealed a higher alpha diversity on the skin of older individuals compared with younger ones. Overall microbiota structure was different between the two age groups, as demonstrated by beta diversity analysis, which also highlighted a high interpersonal variation within older individuals. Furthermore, taxonomic composition analysis showed both an increase in Proteobacteria and a decrease in Actinobacteria on the older skin. At the genus level, older skin exhibited a significant increase in Corynebacterium and a decrease in Propionibacterium relative abundance. CONCLUSIONS: Our study revealed a shift in the distribution of skin microbiota during chronological aging in Western European women. SIGNIFICANCE AND IMPACT OF STUDY: Altogether these results could become the basis to develop new approaches aiming to rebalance the skin microbiota, which is modified during the aging process. PMID- 29791789 TI - Subclavian central venous catheter, complications at insertion AB - Background: Central Venous Catheters (CVC) are used as a tool in critically ill patients requiring hemodynamic monitoring and vasopressor support, as well as in stable patients requiring parenteral nutrition or chemotherapy. Placement of a CVC subclavian (CVCs) can present severe complications, even fatal. The aim of the present study was to determine the success of the placement of CVCs without ultrasonographic guidance and the number and type of complications associated with insertion.of these. Methods: In this retrospective cohort study we included all patient who were submitted to CVCs at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI. The variables studied were: medical indication for the placement, insertion site, duration, withdrawal motive and if there were complications type number and management of these. Results: 283 patients aged 16 95 years were studied. Fifty-five percent of the patients had already had a catheter placed during a previous hospitalization. In 45% of the patients was the first placement, the antecedent of a previous placement did not increase the complications. The indications for the CVCs were: NPT, preoperative use, severe patients, chemotherapy, inability to channel, and plasmapheresis. Conclusions: Placement of a subclavian central venous catheter by trained personnel in patients without risk factors and even without ultrasonographic support is safe and effective, with a success rate of close to 100% in placement, severe complications below 2%, and zero mortality. If the attempts are reduced to two punctures the morbidity can be reduced to almost zero. PMID- 29791790 TI - Hemorrheologic effect of diuretics in the control of blood pressure in the hypertensive patient AB - Background: Diuretics are the first choice as an antihypertensive,because of its efficacy and cost, however its mechanismof action is not well understood. The aim of this work was toanalyze the hemorrheological effect of the diuretics as vasodilatorsin patients with newly diagnosed arterial hypertension. Methods: Patients with hypertension were given diet and exercise recommendations and 25 mg of chlorthalidone per day were prescribed; Hemoglobin/hematocrit, viscosity, and basal nitric oxide (ON) were determined at 15 and 45 days and compared with healthy subjects. Results: We included 28 patients with average age of 48 years old; systolic blood pressure in the treated patients decreased from baseline at 15 days from 130 to 119 mm Hg and at 114 mmHg at 15 to 45 days; diastolic blood pressure decreased from baseline at 15 days from 103 to 97 mm Hg, and at 93 mmHg at 15 to 45 days. The hematocrit increased in both men and women with a statistical significance of the baseline period at 15 days, after that, it remained without significative changes. The viscosity increased similarly to the hematocrit, which conditioned the ON elevation. Conclusions: The increase in hematocrit due to diuretic caused an increase in blood viscosity, which led to an increase in nitric oxide, resulting in lower blood pressure. PMID- 29791791 TI - Risk of lethality due to nosocomial infections in a tertiary-level hospital AB - Background: Infections associated with health care, previously known as nosocomial infections, constitute one of the main causes of morbidity and mortality in hospital. The aim of this study is to estimate the lethality of HAI, as well as the risk of dying from HAI versus mortality by other causes. Methods: We analyzed the historical cohort of IAAS of the Epidemiology service of a tertiary-level hospital, from 2012 to 2017. The incidence analysis and the probability of death of IAAS were made against other causes, as well as the analysis of age, period-cohort of lethality of IAAS. Results: The incidence of IAAS ranged from 27.9 to 31.5 IAAS/1000 person-days between 2012 and 2017, the probability of having an IAAS in ICU is 3.51 (CI95%: 2.93-4.20), p < 0.01, NAVM lethality against any other causes of death had a relative risk (RR) of 6.06 (CI95%: 2.91-12.6) in 2016, RR was 4.01 (CI95%: 1.59-10.09) in ITUAC in 2015, no effect of age, cohort or period in the case of IAAS was identified. Conclusions: IAAS remain to be an important public health problem in our country, without excluding our medical unit, it is important to redirect efforts to reduce them in the medium term. PMID- 29791792 TI - Normalizing Tumor Microenvironment Based on Photosynthetic Abiotic/Biotic Nanoparticles. AB - Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O2 generation in vivo. Under 660 nm laser irradiation, the PLANT system exhibited intracellular O2 generation and the anaerobic respiration of the multicellular tumor spheroid was suppressed by PLANT as well. In vivo, it was found that PLANT could not only normalize the entire metabolic network but also adjust the abnormal structure and function of the tumor vasculature. It was demonstrated that PLANT could significantly enhance the efficacy of phototherapy or antiangiogenesis therapy. This facile approach for normalizing the tumor microenvironment will find great potential in tumor therapy. PMID- 29791793 TI - Assays for Nucleotide Competitive Reversible and Irreversible Inhibitors of Ras GTPases. AB - Although the Ras protein has been seen as a potential target for cancer therapy for the past 30 years, there was a tendency to consider it undruggable until recently. This has changed with the demonstration that small molecules with a specificity for (disease related mutants of) Ras can indeed be found, and some of these molecules form covalent adducts. A subgroup of these molecules can be characterized as competing with binding of the natural ligands GTP and GDP. Because of the distinct properties of Ras and related GTPases, in particular the very high nucleotide affinities and associated very low dissociation rates, assays for characterizing such molecules are not trivial. This is compounded by the fact that Ras family GTPases tend to be thermally unstable in the absence of a bound nucleotide. Here, we show that instead of using the unstable nucleotide free Ras, the protein can be isolated as a 1:1 complex with a modified nucleotide (GDP-beta-methyl ester) with low affinity to Ras. With this nucleotide analogue bound to the protein, testing of inhibitors is made experimentally more convenient and we present assays that allow the rapid assessment of the kinetic constants describing the inhibition process. PMID- 29791794 TI - Photolysis of Mono- and Dichloramines in UV/Hydrogen Peroxide: Effects on 1,4 Dioxane Removal and Relevance in Water Reuse. AB - Growing demands and increasing scarcity of fresh water resources necessitate potable water reuse, which has been implemented with the aid of UV-based advanced oxidation processes (UV/AOPs) that remove potentially hazardous trace organic contaminants from reclaimed water. During the potable reuse treatment process, chloramines are added to prevent membrane fouling that are carried over to the UV/AOP, where hydrogen peroxide (H2O2) is commonly added. However, the impact of chloramines on the photolysis of H2O2 and the overall performance of the UV/AOP remains unknown. This study investigated the impacts of the photochemistry of monochloramine (NH2Cl) and dichloramine (NHCl2) associated with the photolysis of H2O2 on the degradation of 1,4-dioxane (1,4-D), a trace organic contaminant ubiquitous in recycled water. Results indicated that NH2Cl and NHCl2 alone functioned as oxidants upon UV photolysis, which produced HO* and Cl2*- as the two primary oxidative radicals. The speciation of chloramines did not have a significant impact on the degradation kinetics. The inclusion of monochloramine in UV/H2O2 greatly decreased 1,4-D removal efficiency. HO* was the major radical in the mixed H2O2/chloramine system. Results from this study suggest that recognizing the existence of chloramines in UV/H2O2 systems is important for predicting UV/AOP performance in the treatment train of potable reuse. PMID- 29791795 TI - Surface-Acoustic-Wave (SAW)-Driven Device for Dynamic Cell Cultures. AB - In the last few decades, new types of cell cultures have been introduced to provide better cell survival and development, with micro- and nanoenvironmental physicochemical conditions aimed at mimicking those present in vivo. However, despite the efforts made, the systems available to date are often difficult to replicate and use. Here, an easy-to-use surface-acoustic-wave (SAW)-based platform is presented for realizing dynamic cell cultures that is compatible with standard optical microscopes, incubators, and cell-culture dishes. The SAW chip is coupled to a standard Petri dish via a polydimethylsiloxane (PDMS) disc and consists of a lithium niobate (LN) substrate on which gold interdigital transducers (IDTs) are patterned to generate the SAWs and induce acoustic streaming in the dish. SAW excitation is verified and characterized by laser Doppler vibrometry, and the fluid dynamics is studied by microparticle image velocimetry (MUPIV). Heating is measured by an infrared (IR) thermal camera. We finally tested this device with the U-937 monocyte cell line for viability and proliferation and cell-morphological analysis. The data demonstrate that it is possible to induce significant fluid recirculation within the Petri dish while maintaining negligible heating. Remarkably, cell proliferation in this condition was enhanced by 36 +/- 12% with respect to those of standard static cultures. Finally, we show that cell death does not increase and that cell morphology is not altered in the presence of SAWs. This device is the first demonstration that SAW-induced streaming can mechanically improve cell proliferation and further supports the great versatility and biocompatibility of the SAW technology for cell manipulation. PMID- 29791796 TI - Tracking of Engineered Bacteria In Vivo Using Nonstandard Amino Acid Incorporation. AB - The rapidly growing field of microbiome research presents a need for better methods of monitoring gut microbes in vivo with high spatial and temporal resolution. We report a method of tracking microbes in vivo within the gastrointestinal tract by programming them to incorporate nonstandard amino acids (NSAA) and labeling them via click chemistry. Using established machinery constituting an orthogonal translation system (OTS), we engineered Escherichia coli to incorporate p-azido-l-phenylalanine (pAzF) in place of the UAG (amber) stop codon. We also introduced a mutant gene encoding for a cell surface protein (CsgA) that was altered to contain an in-frame UAG codon. After pAzF incorporation and extracellular display, the engineered strains could be covalently labeled via copper-free click reaction with a Cy5 dye conjugated to the dibenzocyclooctyl (DBCO) group. We confirmed the functionality of the labeling strategy in vivo using a murine model. Labeling of the engineered strain could be observed using oral administration of the dye to mice several days after colonization of the gastrointestinal tract. This work sets the foundation for the development of in vivo tracking microbial strategies that may be compatible with noninvasive imaging modalities and are capable of longitudinal spatiotemporal monitoring of specific microbial populations. PMID- 29791797 TI - Modulating Macrophage Polarization through CCR2 Inhibition and Multivalent Engagement. AB - Excessive or prolonged recruitment of inflammatory monocytes to damaged tissue can significantly worsen patient outcomes. Monocytes migrate to sites of tissue inflammation in response to high local concentrations of CCL2, a chemokine that binds to and signals through the CCR2 receptor. While the role of CCR2 in cellular migration is well studied, it is unclear how CCR2 inhibition affects macrophage polarization and if multivalency can increase downstream signaling effects. Using affinity selection with a phage library, we identified a novel single-chain variable fragment (scFv) (58C) that binds specifically and with high affinity to the N-terminal domain of CCR2 ( KD = 59.8 nM). The newly identified 58C-scFv bound to native CCR2 expressed on macrophages and MDA-MB-231 cells, inhibited migration, and induced a pro-inflammatory M1-phenotype in macrophages. The M1/M2 macrophage phenotype ratio for monomeric 58C-scFv was significantly increased over the negative control by 1.0 * 104-fold (iNOS/Arg-1), 5.1 * 104 fold (iNOS/Mgl2), 3.4 * 105-fold (IL-6/Arg-1), and 1.7 * 106-fold (IL-6/Mgl2). The multivalent display of 58C-scFv on liposomes further reduced migration of both cell types by 25-40% and enhanced M1 polarization by 200% over monomeric 58C scFv. These studies demonstrate that CCR2 inhibition polarizes macrophages toward an inflammatory M1 phenotype, and that multivalent engagement of CCR2 increases the effects of 58C-scFv on polarization and migration. These data provide important insights into the role of multivalency in modulating binding, downstream signaling, and cellular fate. PMID- 29791798 TI - Non-Natural Linker Configuration in 2,6-Dipeptidyl-Anthraquinones Enhances the Inhibition of TAR RNA Binding/Annealing Activities by HIV-1 NC and Tat Proteins. AB - The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of anti-retrovirals by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle. Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidyl-anthraquinones as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to the basic side chains. We show here that the non-natural linker configuration imparted unexpected TAR RNA targeting properties to the 2,6-peptidyl-anthraquinones and significantly enhanced their potency. Even if the new compounds were able to interact directly with the NC protein, they manifested a consistently higher affinity for the TAR RNA substrate and their TAR-binding properties mirrored their ability to interfere with NC-TAR interactions. Based on these findings, we propose that the viral Tat protein, sharing the same RNA substrate but acting in distinct phases of the viral life cycle, constitutes an additional druggable target for this class of peptidyl-anthraquinones. The inhibition of Tat-TAR interaction for the test compounds correlated again with their TAR-binding properties, while simultaneously failing to demonstrate any direct Tat-binding capabilities. These considerations highlighted the importance of TAR RNA in the elucidation of their inhibition mechanism, rather than direct protein inhibition. We have therefore identified anti-TAR compounds with dual in vitro inhibitory activity on different viral proteins, demonstrating that it is possible to develop multitarget compounds capable of interfering with processes mediated by the interactions of this essential RNA domain of HIV-1 genome with NC and Tat proteins. PMID- 29791799 TI - Oxidation of Microcystins by Permanganate: pH and Temperature-Dependent Kinetics, Effect of DOM Characteristics, and Oxidation Mechanism Revisited. AB - Oxidative degradation of six representative microcystins (MCs) (MC-RR, -LR, -YR, LF, -LW, and -LA) by potassium permanganate (KMnO4; Mn(VII)) was investigated, focusing on the temperature- and pH-dependent reaction kinetics, the effect of dissolved organic matter (DOM), and the oxidation mechanisms. Second-order rate constants for the reactions of the six MCs with Mn(VII) ( kMn(VII),MC) were determined to be 160.4-520.1 M-1 s-1 (MC-RR > -LR ~ -YR > -LF ~ -LW > -LA) at pH 7.2 and 21 degrees C. The kMn(VII),MC values exhibited activation energies ranging from 15.1 to 22.4 kJ mol-1. With increasing pH from 2 to 11, the kMn(VII),MC values decreased until pH 5, and plateaued over the pH range of 5-11, except for that of MC-YR (which increased at pH > 8). Species-specific second order rate constants were calculated using predicted p Ka values of MCs. The oxidation of MCs in natural waters was accurately predicted by the kinetic model using kMn(VII),MC and Mn(VII) exposure (?[Mn(VII)]dt) values. Among different characteristics of DOM in natural waters, UV254, SUVA254, and the abundance of humic-like substances characterized by fluorescence spectroscopy exhibited good correlation with ?[Mn(VII)]dt. A thorough product study of MC-LR oxidation by Mn(VII) was performed using liquid chromatography-mass spectrometry. PMID- 29791800 TI - Tip-Enhanced Raman Scattering from Nanopatterned Graphene and Graphene Oxide. AB - Tip-enhanced Raman spectroscopy (TERS) is particularly sensitive to analytes residing at plasmonic tip-sample nanojunctions, where the incident and scattered optical fields may be localized and optimally enhanced. However, the enhanced local electric fields in this so-called gap-mode TERS configuration are nominally orthogonal to the sample plane. As such, any given Raman active vibrational eigenstate needs to have projections (of its polarizability derivative tensor elements) along the sample normal to be detectable via TERS. The faint TERS signals observed from two prototypical systems, namely, pristine graphene and graphene oxide are a classical example of the aforementioned rather restrictive TERS selection rules in this context. In this study, we demonstrate that nanoindentation, herein achieved using pulsed-force lithography with a sharp single-crystal diamond atomic force microscope probe, may be used to locally enhance TERS signals from graphene and graphene oxide flakes on gold. Nanoindentation locally perturbs the otherwise flat graphene structure and introduces out-of-plane protrusions that generate enhanced TERS. Although our approach is nominally invasive, we illustrate that the introduced nanodefects are highly localized, as evidenced by TERS nanoscale chemical mapping. As such, the described protocol may be used to extend and generalize the applicability of TERS for the rapid identification of two-dimensional material systems on the nanoscale. PMID- 29791801 TI - Magnetically Controlled Liposome Aggregates for On-Demand Release of Reactive Payloads. AB - A colloidal system able to act as a miniature reactor for on-demand release of reactive payloads has been demonstrated. The system is based on submicrometer aggregates consisting of anionic liposomes that act as storage reservoirs for the reactants, superparamagnetic iron oxide nanoparticles (SPIONs) that enable magnetic positioning in space and controlled release of reactants from the liposomes by radiofrequency stimulation, and an oppositely charged polyelectrolyte (poly-l-lysine) that keeps the constituent elements within the aggregates at a defined ratio. The kinetics of liposome-PLL-SPION heteroaggregation was systematically mapped and a suitable composition of the liposome bilayer was found such that the system exhibits stability at ambient conditions and radiofrequency triggered release at physiological temperature. The functionality of the system was demonstrated using a reaction between resazurin and ascorbic acid. The ability to release the reactants on-demand at defined time points was demonstrated. The system opens up opportunities for the controlled local delivery of unstable of highly bioactive molecules produced in situ and on demand from stable precursors. PMID- 29791802 TI - The Power of Shielding: Low Toxicity and High Transfection Performance of Cationic Graft Copolymers Containing Poly(2-oxazoline) Side Chains. AB - We show the potential of oligo(2-ethyl-2-oxazoline) (Oxn)-shielded graft copolymers of (2-aminoethyl)-methacrylate and N-methyl-(2-aminoethyl) methacrylate for pDNA delivery in HEK cells. For the effect of grafting density and side chain length concerning improved transfection properties through the concept of shielding to be investigated, copolymers were synthesized via the macromonomer method using a combination of cationic ring opening polymerization and reversible addition-fragmentation chain transfer polymerization to vary the degree of grafting (DG = 10 and 30%) as well as the side chain degree of polymerization (DP = 5 and 20). Investigations of the polyplex formation, in vitro flow cytometry, and confocal laser scanning microscopy measurements on the copolymer library revealed classical shielding properties of the Ox side chains, including highly reduced cytotoxicity and a partial decrease in transfection efficiency, as also reported for polyethylene glycol shielding. In terms of the transfection efficiency, the best performing copolymers (A- g-Ox5(10) and M- g Ox5(10)) revealed equal or better performances compared to those of the corresponding homopolymers. In particular, the graft copolymers with low DG and side chain DP transfected well with over 10-fold higher IC50 values. In contrast, a DG of 30% resulted in a loss of transfection efficiency due to missing ability for endosomal release, and a side chain DP of 20 hampered the cellular uptake. PMID- 29791803 TI - Bacteria-Activated Janus Particles Driven by Chemotaxis. AB - In the development of biocompatible nano-/micromotors for drug and cargo delivery, motile bacteria represent an excellent energy source for biomedical applications. Despite intense research of the fabrication of bacteria-based motors, how to effectively utilize the instinctive responses of bacteria to environmental stimuli in the fabrication process, particularly, chemotaxis, remains an urgent and critical issue. Here, by developing a molecular-dynamics model of bacterial chemotaxis, we present an investigation of the transport of a bacteria-activated Janus particle driven by chemotaxis. Upon increasing the stimuli intensity, we find that the transport of the Janus particle undergoes an intriguing second-order state transition: from a composite random walk, combining power-law-distributed truncated Levy flights with Brownian jiggling, to an enhanced directional transport with size-dependent reversal of locomotion. A state diagram of Janus-particle transport depending on the stimuli intensity and particle size is presented, which allows approaches to realize controllable and predictable propulsion directions. The physical mechanism of these transport behaviors is revealed by performing a theoretical modeling based on the bacterial noise and Janus geometries. Our findings could provide a fundamental insight into the physics underlying the transport of anisotropic particles driven by microorganisms and highlight stimulus-response techniques and asymmetrical design as a versatile strategy to possess a wide array of potential applications for future biocompatible nano-/microdevices. PMID- 29791804 TI - Environmentally Relevant Freeze-Thaw Cycles Enhance the Redox-Mediated Morphological Changes of Silver Nanoparticles. AB - Silver nanoparticles (AgNPs) are inevitably released into natural systems, particularly into aquatic environments, where they are oxidized and release Ag+, which is reduced back to AgNPs. Environmental freeze-thaw cycles or freezing may accelerate the dynamic transformation between AgNPs and Ag+. Herein, the significant morphological changes caused by freezing treatments were assessed by UV-vis spectroscopy and high-resolution transmission electron microscopy, which revealed that reductive regeneration, particle fusion, and coalescence of the AgNPs occurred. In addition, a stable Ag isotope was used to track the AgNP redox reaction, which was found to be accelerated under freezing and freeze-thaw cycles relative to the reaction of particles stored at a normal temperature (4 degrees C, 25 degrees C). Furthermore, natural organic matter was found to stabilize the particle morphology. Ca2+ and Cl- intensified the morphological changes and redox reaction through Ca2+-induced particle coalescence and Cl--enhanced reduction of Ag+ during the freeze-thaw treatment. These physicochemical changes also occurred for an environmentally relevant concentration of AgNPs (50 ng L-1) in simulated environmental conditions and natural water samples after freeze-thaw cycles. Since the morphological changes and redox acceleration induced by environmental freezing conditions could dramatically influence the mobility, bioavailability, toxicity, and environmental fate of AgNPs, the freeze-thaw-induced effects should be considered in the environmental risk assessment of AgNPs. PMID- 29791805 TI - Identifying the Nonradical Mechanism in the Peroxymonosulfate Activation Process: Singlet Oxygenation Versus Mediated Electron Transfer. AB - Select persulfate activation processes were demonstrated to initiate oxidation not reliant on sulfate radicals, although the underlying mechanism has yet to be identified. This study explored singlet oxygenation and mediated electron transfer as plausible nonradical mechanisms for organic degradation by carbon nanotube (CNT)-activated peroxymonosulfate (PMS). The degradation of furfuryl alcohol (FFA) as a singlet oxygen (1O2) indicator and the kinetic retardation of FFA oxidation in the presence of l-histidine and azide as 1O2 quenchers apparently supported a role of 1O2 in the CNT/PMS system. However, the 1O2 scavenging effect was ascribed to a rapid PMS depletion by l-histidine and azide. A comparison of CNT/PMS and photoexcited Rose Bengal (RB) excluded the possibility of singlet oxygenation during heterogeneous persulfate activation. In contrast to the case of excited RB, solvent exchange (H2O to D2O) did not enhance FFA degradation by CNT/PMS and the pH- and substrate-dependent reactivity of CNT/PMS did not reflect the selective nature of 1O2. Alternatively, concomitant PMS reduction and trichlorophenol oxidation were achieved when PMS and trichlorophenol were physically separated in two chambers using a conductive vertically aligned CNT membrane. This result suggested that CNT-mediated electron transfer from organics to persulfate was primarily responsible for the nonradical degradative route. PMID- 29791806 TI - Seasonal dynamics of the bacterioplankton community in a large, shallow, highly dynamic freshwater lake. AB - The spatiotemporal shifts of the bacterioplankton community can mirror their transition of functional traits in an aquatic ecosystem. However, the spatiotemporal variation of the bacterioplankton community composition structure (BCCS) within a large, shallow, highly dynamic freshwater lake is still poorly understood. Here, we examined the seasonal and spatial variability of the BCCs within Poyang Lake by sequencing the 16S rRNA gene amplicon to explore how hydrological changes affect the BCCs. Principal coordinate analysis showed that the BCCs varied significantly among four sampling seasons, but not spatially. The seasonal changes of the BCCs were mainly attributed to the differences between autumn and spring-winter. Higher alpha diversity indices were observed in autumn. Redundancy analysis indicated that the BCCs co-variated with water level, pH, temperature, total phosphorus, ammoniacal nitrogen, electrical conductivity, total nitrogen, and turbidity. Among them, water level was the key determinant separating autumn BCCs from the BCCs in other seasons. A significantly lower relative abundance of Burkholderiales (betI and betVII) and a higher relative abundance of Actinomycetales (acI, acTH1, and acTH2) were found in autumn than in other seasons. Overall, our results suggest that water level changes associated with pH, temperature, and nutrient status shaped the seasonal patterns of the BCCs within Poyang Lake. PMID- 29791807 TI - Beliefs About Behavioral Determinants of Obesity in Appalachia, 2011-2014. AB - The populations of many Appalachian communities have high rates of unhealthy body weight. This study aimed to identify differences in beliefs about obesity between Appalachians and non-Appalachians. Our analyses explored health beliefs and behaviors among US adults aged >=18 (n = 14 451) who responded to the Health Information National Trends Survey (2011-2014), of whom 1015 (8%) resided within the 420 counties recognized as Appalachian by the Appalachian Regional Commission. Using weighted regression analyses and controlling for sociodemographic characteristics and general health, we determined that self reported body mass index was higher among Appalachians than among non Appalachians ( B = 0.75, P = .03, 95% confidence interval, 0.08-1.47) and that Appalachians were less likely than non-Appalachians to believe that lifestyle factors were related to obesity ( B = -0.37, P = .03, 95% confidence interval, 0.04 to -0.71). Results suggest that Appalachians may regard behavioral prevention differently from non-Appalachians, perhaps with less confidence in the effectiveness of certain behaviors to reduce obesity risk. Future research may determine whether such beliefs could complicate efforts to encourage healthy lifestyles throughout the region. PMID- 29791808 TI - Pseudomonads contribute to regulation of Pratylenchus penetrans (Nematoda) populations on apple. AB - Inoculation with antagonistic soil microorganisms has shown potential to suppress replant disease of apple in orchard soils. Pseudomonas spp. may have the potential to reduce Pratylenchus penetrans populations on apple. Pseudomonas spp. were isolated from the rhizosphere of sweet cherry and screened for antagonistic characteristics. Two highly antagonistic Pseudomonas isolates, P10-32 and P10-42, were evaluated for growth promotion of apple seedlings, suppression of P. penetrans populations, and root colonization in soil from three orchards. During the isolate screening, Pseudomonas fluorescens P10-32 reduced in vitro growth of fungal pathogens, had protease activity, had capacity to produce pyrrolnitrin, suppressed P. penetrans populations, and increased plant biomass. Pseudomonas fluorescens P10-42 reduced in vitro growth of fungal pathogens, had protease activity, suppressed P. penetrans populations, and increased plant biomass. In potted orchard soil, inoculating apple with P. fluorescens P10-32 suppressed P. penetrans populations in one of the three soils examined. Inoculation with P. fluorescens P10-42 improved plant growth in two of the soils and suppressed P. penetrans abundance in one soil. In one of the soils, P. fluorescens P10-42 was detected on the roots 56 days postinoculation. Overall, we conclude that Pseudomonas spp. play a role in suppressing P. penetrans on apple in orchard soil. PMID- 29791809 TI - Phagocytosis: what's on the menu? AB - Phagocytosis is an evolutionarily conserved process. In Protozoa, phagocytosis fulfills a feeding mechanism, while in Metazoa, phagocytosis diversified to play multiple organismal roles, including immune defence, tissue homeostasis, and remodeling. Accordingly, phagocytes display a high level of plasticity in their capacity to recognize, engulf, and process targets that differ in composition and morphology. Here, we review how phagocytosis adapts to its multiple roles and discuss in particular the effect of target morphology in phagocytic uptake and phagosome maturation. PMID- 29791810 TI - Anal fibropapillomas containing bovine papillomavirus type 2 DNA in two groups of heifers. AB - CASE HISTORY Anal warts were observed in heifers in two unrelated groups of animals. Heifers in one group developed visible warts 4 months after manual rectal examination and heifers in the other group developed warts 5 months after examination using a hand-held rectal ultrasound probe. CLINICAL FINDINGS Large exophytic proliferative anal masses were observed in 5/15 (33%) heifers in one group and 13/149 (9%) heifers in the second group. Heifers in the second group were also noted to have similar masses on the underside of the tail at sites previously used for venepuncture and some of the heifers had skin warts. Despite the large size of the anal masses, none of the heifers showed clinical signs of systemic illness. HISTOPATHOLOGICAL FINDINGS An anal mass was removed from one heifer in each of the two groups. Sections from both masses showed hyperplastic epithelium covering a proliferation of well-differentiated fibroblasts consistent with fibropapillomas. Small numbers of cells within the epidermis had clear cytoplasm with clumped keratohyalin granules. MOLECULAR BIOLOGY Bovine papillomavirus (BPV) type 2 DNA was amplified from both fibropapillomas by PCR. DIAGNOSIS Multiple anal fibropapillomas associated with BPV-2. CLINICAL RELEVANCE Bovine anal fibropapillomas have only been reported in heifers that have undergone rectal examination, and infection of anal microabrasions in an immunologically naive animal appears to be associated with disease development. The source and method of spread of BPV-2 within these groups could not be determined. However spread of BPV-2 within the groups by the veterinarian performing rectal examinations may have been most likely. While these fibropapillomas had a dramatic appearance, like fibropapillomas elsewhere on the body, they did not have any significant effect on the health of the affected heifers. As these lesions can be diagnosed by clinical examination and self resolve without treatment, it is important that veterinarians are aware of this rare manifestation of papillomavirus infection of cattle. PMID- 29791811 TI - The putative transient receptor potential channel protein encoded by the orf19.4805 gene is involved in cation sensitivity, antifungal tolerance, and filamentation in Candida albicans. AB - Transient receptor potential (TRP) channels, an ancient family of cation channels, are highly conserved in eukaryotes and play various physiological functions, ranging from sensation of ion homeostasis to reception of pain and vision. Calcium-permeable TRP channels have been identified from the plant Arabidopsis thaliana (AtCsc1) and the budding yeast Saccharomyces cerevisiae (ScCsc1). In this study, we characterized the functions of the Csc1 homolog, orf19.4805, in Candida albicans. Orf19.4805 is a protein of 866 amino acids and 11 transmembrane domains, which shares 49% identity (69% similarity) in amino acid sequence with ScRsn1. Here, we demonstrate that deletion of the orf19.4805 gene causes C. albicans cells to be sensitive to SDS (sodium dodecyl sulfate) and antifungal drugs, and tolerance to zinc, manganese, and cadmium ions. Candida albicans cells lacking orf19.4805 show a defect in filamentation in vitro. Therefore, orf19.4805 is involved in the regulation of cation homeostasis and filamentation in C. albicans. PMID- 29791812 TI - Automated oestrus detection using multimetric behaviour recognition in seasonal calving dairy cattle on pasture. AB - AIM To evaluate the performance of a novel accelerometer-based oestrus detection system (ODS) for dairy cows on pasture, in comparison with measurement of concentrations of progesterone in milk, ultrasonographic examination of ovaries and farmer observations. METHODS Mixed-breed lactating dairy cows (n=109) in a commercial, seasonal-calving herd managed at pasture under typical farming conditions in Ireland, were fitted with oestrus detection collars 3 weeks prior to mating start date. The ODS performed multimetric analysis of eight different motion patterns to generate oestrus alerts. Data were collected during the artificial insemination period of 66 days, commencing on 16 April 2015. Transrectal ultrasonographic examinations of the reproductive tract and measurements of concentrations of progesterone in milk were used to confirm oestrus events. Visual observations by the farmer and the number of theoretically expected oestrus events were used to evaluate the number of false negative ODS alerts. The percentage of eligible cows that were detected in oestrus at least once (and were confirmed true positives) was calculated for the first 21, 42 and 63 days of the insemination period. RESULTS During the insemination period, the ODS generated 194 oestrus alerts and 140 (72.2%) were confirmed as true positives. Six confirmed oestrus events recognised by the farmer did not generate ODS alerts. The positive predictive value of the ODS was 72.2 (95% CI=65.3 78.4)%. To account for oestrus events not identified by the ODS or the farmer, four theoretical missed oestrus events were added to the false negatives. Estimated sensitivity of the automated ODS was 93.3 (95% CI=88.1-96.8)%. The proportion of eligible cows that were detected in oestrus during the first 21 days of the insemination period was 92/106 (86.8%), and during the first 42 and 63 days of the insemination period was 103/106 (97.2%) and 105/106 (99.1%), respectively. CONCLUSIONS and CLINICAL RELEVANCE The ODS under investigation was suitable for oestrus detection in dairy cows on pasture and showed a high sensitivity of oestrus detection. Multimetric analysis of behavioural data seems to be the superior approach to developing and improving ODS for dairy cows on pasture. Due to a high proportion of false positive alerts, its use as a stand alone system for oestrus detection cannot be recommended. As it is the first time the system was investigated, testing on other farms would be necessary for further validation. PMID- 29791813 TI - Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. AB - BACKGROUND: Previous studies showed a higher incidence of lung cancer among young women than among young men in the United States. Whether this pattern has continued in contemporary birth cohorts and, if so, whether it can be fully explained by sex differences in smoking behaviors are unknown. METHODS: We examined the nationwide population-based incidence of lung cancer according to sex, race or ethnic group, age group (30 to 34, 35 to 39, 40 to 44, 45 to 49, and 50 to 54 years), year of birth (1945 to 1980), and calendar period of diagnosis (1995-1999, 2000-2004, 2005-2009, and 2010-2014), and we calculated female-to male incidence rate ratios. We also examined the prevalence of cigarette smoking, using data from the National Health Interview Survey from 1970 to 2016. RESULTS: Over the past two decades, the age-specific incidence of lung cancer has generally decreased among both men and women 30 to 54 years of age in all races and ethnic groups, but the declines among men have been steeper. Consequently, among non-Hispanic whites, the female-to-male incidence rate ratios increased, exceeding 1.0 in the age groups of 30 to 34, 35 to 39, 40 to 44, and 45 to 49 years. For example, the female-to-male incidence rate ratio among whites 40 to 44 years of age increased from 0.88 (95% confidence interval [CI], 0.84 to 0.92) during the 1995-1999 period to 1.17 (95% CI, 1.11 to 1.23) during the 2010-2014 period. The crossover in sex-specific rates occurred among non-Hispanic whites born since 1965. Sex-specific incidence rates converged among non-Hispanic blacks, Hispanics, and non-Hispanic Asians and Pacific Islanders but crossed over from a higher incidence among men to a higher incidence among women only among Hispanics. The prevalence of cigarette smoking among women born since 1965 has approached, but generally not exceeded, the prevalence among men. CONCLUSIONS: The patterns of historically higher incidence rates of lung cancer among men than among women have reversed among non-Hispanic whites and Hispanics born since the mid-1960s, and they are not fully explained by sex differences in smoking behaviors. Future studies are needed to identify reasons for the higher incidence of lung cancer among young women. (Funded by the American Cancer Society.). PMID- 29791815 TI - Incidence of Cellulitis among Children with Primary Lymphedema. PMID- 29791814 TI - Case 16-2018: A 45-Year-Old Man with Fever, Thrombocytopenia, and Elevated Aminotransferase Levels. PMID- 29791817 TI - p53 and Me. PMID- 29791816 TI - Fast Forward - Neoadjuvant Cancer Immunotherapy. PMID- 29791818 TI - Retinal Vasculitis in Takayasu's Arteritis. PMID- 29791819 TI - ECMO for Severe ARDS. PMID- 29791820 TI - Patient Age and the Seasonal Pattern of Onset of Kawasaki's Disease. PMID- 29791821 TI - Tinea Capitis in a Newborn. PMID- 29791823 TI - Doughnuts and Discounts - Changes to Medicare Part D under the Bipartisan Budget Act of 2018. PMID- 29791824 TI - Consequences of the 340B Drug Pricing Program. PMID- 29791825 TI - Inhaled Glucocorticoids in Asthma. PMID- 29791826 TI - Subscribing to Your Patients - Reimagining the Future of Electronic Health Records. PMID- 29791822 TI - Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. AB - BACKGROUND: The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS: In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS: At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (+/-SD) of 6.5+/-9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2). CONCLUSIONS: Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Developpement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .). PMID- 29791828 TI - Diagnosis and Management of the Antiphospholipid Syndrome. PMID- 29791827 TI - A Shocking Turn of Events. PMID- 29791829 TI - Burosumab Therapy in Children with X-Linked Hypophosphatemia. AB - BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. RESULTS: The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. CONCLUSIONS: In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ). PMID- 29791830 TI - Learning from a Trial Stopped by a Data and Safety Monitoring Board. PMID- 29791831 TI - The Lymph Node and the Metastasis. PMID- 29791832 TI - Rationale, Opportunities, and Reality of Biosimilar Medications. PMID- 29791833 TI - Maternal and postnatal high-fat diets with high ?6:?3 ratios affect the reproductive performance of male offspring in the mouse. AB - High-fat diets (HFDs) are an acknowledged risk factor for male subfertility, but the underlying mechanisms remain unclear. In the present study we compared the effects of two HFDs with different omega6:omega3 ratios, one enriched with soy oil (SOD; omega6:omega3=9.62) and another enriched with sunflower oil (SFOD; omega6:omega3=51.55), with those of a commercial diet (CD; omega6:omega3=19.87), supplied from pregnancy to adulthood, on morphometric parameters and reproductive performance in adult male mice (recommended omega6:omega3 for rodents=1-6). Bodyweight was significantly higher in the SFOD than CD group, and relative testicular weight was significantly lower in the SFOD than the other two groups. SFOD altered sperm performance: it reduced sperm viability (mean+/-s.e.m.; 76.00+/-1.35% vs 82.50+/-1.45% and 80.63+/-1.00% in the SFOD vs CD and SOD groups respectively; P<0.05) and increased the percentage of immature spermatozoa (71.88+/-7.17% vs 51.38+/-5.87% and 48.00+/-5.72% in the SFOD vs CD and SOD groups respectively; P<0.05). The epididymal omega6:omega3 ratio was higher in the SFOD versus CD and SOD groups, whereas the unsaturation index was higher in the SOD and SFOD groups than in CD group. Sperm membrane integrity was diminished in both the SOD and SFOD groups, but there was no difference in sperm reactive oxygen species production in these two groups compared with the CD group. The fertilisation rate was lower in the SFOD compared with the CD and SOD groups. In conclusion, although both HFDs affected sperm quality, the fertilising ability was more altered by the excessive dietary omega6:omega3 ratio than by the net omega6 content. PMID- 29791836 TI - Trpv4 Mediates Hypotonic Inhibition of Central Osmosensory Neurons via Taurine Gliotransmission. AB - The maintenance of hydromineral homeostasis requires bidirectional detection of changes in extracellular fluid osmolality by primary osmosensory neurons (ONs) in the organum vasculosum laminae terminalis (OVLT). Hypertonicity excites ONs in part through the mechanical activation of a variant transient receptor potential vanilloid-1 channel (dn-Trpv1). However, the mechanism by which local hypotonicity inhibits ONs in the OVLT remains unknown. Here, we show that hypotonicity can reduce the basal activity of dn-Trpv1 channels and hyperpolarize acutely isolated ONs. Surprisingly, we found that mice lacking dn-Trpv1 maintain normal inhibitory responses to hypotonicity when tested in situ. In the intact setting, hypotonicity inhibits ONs through a non-cell-autonomous mechanism that involves glial release of the glycine receptor agonist taurine through hypotonicity activated anion channels (HAAC) that are activated subsequent to Ca2+ influx through Trpv4 channels. Our study clarifies how Trpv4 channels contribute to the inhibition of OVLT ONs during hypotonicity in situ. PMID- 29791834 TI - Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus. AB - Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles for noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization has lagged. We profiled mouse noradrenergic neurons in vivo, defining over 3,000 high-confidence transcripts expressed therein, including druggable receptors. We uncovered remarkable sex differences in gene expression, including elevated expression of the EP3 receptor in females-which we leverage to illustrate the behavioral and pharmacologic relevance of these findings-and of Slc6a15 and Lin28b, both major depressive disorder (MDD)-associated genes. Broadly, we present a means of transcriptionally profiling locus coeruleus under baseline and experimental conditions. Our findings underscore the need for preclinical work to include both sexes and suggest that sex differences in noradrenergic neurons may underlie behavioral differences relevant to disease. PMID- 29791835 TI - Nicotinic Cholinergic Receptors in VTA Glutamate Neurons Modulate Excitatory Transmission. AB - Ventral tegmental area (VTA) glutamate neurons are important components of reward circuitry, but whether they are subject to cholinergic modulation is unknown. To study this, we used molecular, physiological, and photostimulation techniques to examine nicotinic acetylcholine receptors (nAChRs) in VTA glutamate neurons. Cells in the medial VTA, where glutamate neurons are enriched, are responsive to acetylcholine (ACh) released from cholinergic axons. VTA VGLUT2+ neurons express mRNA and protein subunits known to comprise heteromeric nAChRs. Electrophysiology, coupled with two-photon microscopy and laser flash photolysis of photoactivatable nicotine, was used to demonstrate nAChR functional activity in the somatodendritic subcellular compartment of VTA VGLUT2+ neurons. Finally, optogenetic isolation of intrinsic VTA glutamatergic microcircuits along with gene-editing techniques demonstrated that nicotine potently modulates excitatory transmission within the VTA via heteromeric nAChRs. These results indicate that VTA glutamate neurons are modulated by cholinergic mechanisms and participate in the cascade of physiological responses to nicotine exposure. PMID- 29791837 TI - Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation. AB - Zinc finger protein ZFP24, formerly known as ZFP191, is essential for oligodendrocyte maturation and CNS myelination. Nevertheless, the mechanism by which ZFP24 controls these processes is unknown. We demonstrate that ZFP24 binds to a consensus DNA sequence in proximity to genes important for oligodendrocyte differentiation and CNS myelination, and we show that this binding enhances target gene expression. We also demonstrate that ZFP24 DNA binding is controlled by phosphorylation. Phosphorylated ZFP24, which does not bind DNA, is the predominant form in oligodendrocyte progenitor cells. As these cells mature into oligodendrocytes, the non-phosphorylated, DNA-binding form accumulates. Interestingly, ZFP24 displays overlapping genomic binding sites with the transcription factors MYRF, SOX10, and OLIG2, which are known to control oligodendrocyte differentiation. Our findings provide a mechanism by which dephosphorylation of ZFP24 mediates its binding to regulatory regions of genes important for oligodendrocyte maturation, controls their expression, and thereby regulates oligodendrocyte differentiation and CNS myelination. PMID- 29791838 TI - Dorsolateral Striatum Engagement Interferes with Early Discrimination Learning. AB - In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning. PMID- 29791839 TI - Ubiquitylation Dynamics of the Clock Cell Proteome and TIMELESS during a Circadian Cycle. AB - Circadian clocks have evolved as time-measuring molecular devices to help organisms adapt their physiology to daily changes in light and temperature. Transcriptional oscillations account for a large fraction of rhythmic protein abundance. However, cycling of various posttranslational modifications, such as ubiquitylation, also contributes to shape the rhythmic protein landscape. In this study, we used an in vivo ubiquitin labeling assay to investigate the circadian ubiquitylated proteome of Drosophila melanogaster. We find that cyclic ubiquitylation affects MEGATOR (MTOR), a chromatin-associated nucleoporin that, in turn, feeds back to regulate the core molecular oscillator. Furthermore, we show that the ubiquitin ligase subunits CULLIN-3 (CUL-3) and SUPERNUMERARY LIMBS (SLMB) cooperate for ubiquitylating the TIMELESS protein. These findings stress the importance of ubiquitylation pathways in the Drosophila circadian clock and reveal a key component of this system. PMID- 29791841 TI - Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans. AB - Candida albicans is a leading cause of death due to fungal infection. Treatment of systemic candidiasis often relies on echinocandins, which disrupt cell wall synthesis. Resistance is readily acquired via mutations in the drug target gene, FKS1. Both basal tolerance and resistance to echinocandins require cellular stress responses. We performed a systematic analysis of 3,030 C. albicans mutants to define circuitry governing cellular responses to echinocandins. We identified 16 genes for which deletion or transcriptional repression enhanced echinocandin susceptibility, including components of the Pkc1-MAPK signaling cascade. We discovered that the molecular chaperone Hsp90 is required for the stability of Pkc1 and Bck1, establishing key mechanisms through which Hsp90 mediates echinocandin resistance. We also discovered that perturbation of the CCT chaperonin complex causes enhanced echinocandin sensitivity, altered cell wall architecture, and aberrant septin localization. Thus, we provide insights into the mechanisms by which cellular chaperones enable crucial responses to echinocandin-induced stress. PMID- 29791840 TI - Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex. AB - Impulses generated by a multicellular, bioelectric signaling center termed the sinoatrial node (SAN) stimulate the rhythmic contraction of the heart. The SAN consists of a network of electrochemically oscillating pacemaker cells encased in a heterogeneous connective tissue microenvironment. Although the cellular composition of the SAN has been a point of interest for more than a century, the biological processes that drive the tissue-level assembly of the cells within the SAN are unknown. Here, we demonstrate that the SAN's structural features result from a developmental process during which mesenchymal cells derived from a multipotent progenitor structure, the proepicardium, integrate with and surround pacemaker myocardium. This process actively remodels the forming SAN and is necessary for sustained electrogenic signal generation and propagation. Collectively, these findings provide experimental evidence for how the microenvironmental architecture of the SAN is patterned and demonstrate that proper cellular arrangement is critical for cardiac pacemaker biorhythmicity. PMID- 29791842 TI - Plant Endocytosis Requires the ER Membrane-Anchored Proteins VAP27-1 and VAP27-3. AB - Through yet-undefined mechanisms, the plant endoplasmic reticulum (ER) has a critical role in endocytosis. The plant ER establishes a close association with endosomes and contacts the plasma membrane (PM) at ER-PM contact sites (EPCSs) demarcated by the ER membrane-associated VAMP-associated-proteins (VAP). Here, we investigated two plant VAPs, VAP27-1 and VAP27-3, and found an interaction with clathrin and a requirement for the homeostasis of clathrin dynamics at endocytic membranes and endocytosis. We also demonstrated direct interaction of VAP27 proteins with phosphatidylinositol-phosphate lipids (PIPs) that populate endocytic membranes. These results support that, through interaction with PIPs, VAP27-proteins bridge the ER with endocytic membranes and maintain endocytic traffic, likely through their interaction with clathrin. PMID- 29791844 TI - Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3. AB - T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORgammat, but the underlying mechanism is not well understood. Nuclear receptor mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-beta/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC 3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORgammat-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORgammat-dependent gene expression in Th17 cell-driven autoimmune diseases. PMID- 29791845 TI - Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability. AB - T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs and the reutilization of biomolecules, processes that require active participation of metabolite transporters. Here, we show that equilibrative nucleoside transporter 3 (ENT3) is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells. ENT3 deficiency leads to an enlarged and disturbed lysosomal compartment, resulting in accumulation of surplus mitochondria, elevation of intracellular reactive oxygen species, and DNA damage in T cells. Our results identify ENT3 as a vital metabolite transporter that supports T cell homeostasis and activation by regulating lysosomal integrity and the availability of nucleosides. Moreover, we uncovered that T cell lysosomes are an important source of salvaged metabolites for survival and proliferation. PMID- 29791843 TI - Cell-Cycle Regulation of Dynamic Chromosome Association of the Condensin Complex. AB - Eukaryotic cells inherit their genomes in the form of chromosomes, which are formed from the compaction of interphase chromatin by the condensin complex. Condensin is a member of the structural maintenance of chromosomes (SMC) family of ATPases, large ring-shaped protein assemblies that entrap DNA to establish chromosomal interactions. Here, we use the budding yeast Saccharomyces cerevisiae to dissect the role of the condensin ATPase and its relationship with cell-cycle regulated chromosome binding dynamics. ATP hydrolysis-deficient condensin binds to chromosomes but is defective in chromosome condensation and segregation. By modulating the ATPase, we demonstrate that it controls condensin's dynamic turnover on chromosomes. Mitosis-specific phosphorylation of condensin's Smc4 subunit reduces the turnover rate. However, reducing turnover by itself is insufficient to compact chromosomes. We propose that condensation requires fine tuned dynamic condensin interactions with more than one DNA. These results enhance our molecular understanding of condensin function during chromosome condensation. PMID- 29791846 TI - Myosin IIa Promotes Antibody Responses by Regulating B Cell Activation, Acquisition of Antigen, and Proliferation. AB - B cell responses are regulated by antigen acquisition, processing, and presentation to helper T cells. These functions are thought to depend on contractile activity of non-muscle myosin IIa. Here, we show that B cell-specific deletion of the myosin IIa heavy chain reduced the numbers of bone marrow B cell precursors and splenic marginal zone, peritoneal B1b, and germinal center B cells. In addition, myosin IIa-deficient follicular B cells acquired an activated phenotype and were less efficient in chemokinesis and extraction of membrane presented antigens. Moreover, myosin IIa was indispensable for cytokinesis. Consequently, mice with myosin IIa-deficient B cells harbored reduced serum immunoglobulin levels and did not mount robust antibody responses when immunized. Altogether, these data indicate that myosin IIa is a negative regulator of B cell activation but a positive regulator of antigen acquisition from antigen presenting cells and that myosin IIa is essential for B cell development, proliferation, and antibody responses. PMID- 29791847 TI - Neutrophils Provide a Favorable IL-1-Mediated Immunometabolic Niche that Primes GLUT4 Translocation and Performance in Skeletal Muscles. AB - Metabolic immunomodulation involving IL-1 has been investigated for unfavorable metabolic effects, including obesity, but a potentially favorable role for IL-1 remains unclear. Here, we find mechanistic interactions between working skeletal muscles and locally recruited neutrophils expressing IL-1beta, which supports muscle performance through priming exercise-dependent GLUT4 translocation. Thus, during exercise, both IL-1alpha/beta-deficient and neutrophil-depleted mice similarly exhibit increased fatigability associated with impaired muscle glucose homeostasis due to GLUT4 dysregulation. Deficiency of IL-1-producing neutrophils results in intrinsic abnormalities represented by aberrant Rac1 signaling and irregular GLUT4-storage vesicles, suggesting that these properties are maintained by local IL-1 produced by recruited neutrophils upon exercise, possibly on a daily basis. We propose that neutrophils are highly engaged in skeletal muscle performance via IL-1 regulation, which coordinates favorable inflammatory microenvironments supporting muscle glucose metabolism. PMID- 29791848 TI - Pre-synaptic Muscarinic Excitation Enhances the Discrimination of Looming Stimuli in a Collision-Detection Neuron. AB - Visual neurons that track objects on a collision course are often finely tuned to their target stimuli because this is critical for survival. The presynaptic neural networks converging on these neurons and their role in tuning them remain poorly understood. We took advantage of well-known characteristics of one such neuron in the grasshopper visual system to investigate the properties of its presynaptic input network. We find the structure more complex than hitherto realized. In addition to dynamic lateral inhibition used to filter out background motion, presynaptic circuits include normalizing inhibition and excitatory interactions mediated by muscarinic acetylcholine receptors. These interactions preferentially boost responses to coherently expanding visual stimuli generated by colliding objects, as opposed to spatially incoherent controls, helping to discriminate between them. Hence, in addition to active dendritic conductances within collision-detecting neurons, multiple layers of inhibitory and excitatory presynaptic connections are needed to finely tune neural circuits for collision detection. PMID- 29791849 TI - Activation of Entorhinal Cortical Projections to the Dentate Gyrus Underlies Social Memory Retrieval. AB - Social interactions are essential to our mental health, and a deficit in social interactions is a hallmark characteristic of numerous brain disorders. Various subregions within the medial temporal lobe have been implicated in social memory, but the underlying mechanisms that tune these neural circuits remain unclear. Here, we demonstrate that optical activation of excitatory entorhinal cortical perforant projections to the dentate gyrus (EC-DG) is necessary and sufficient for social memory retrieval. We further show that inducible disruption of p21 activated kinase (PAK) signaling, a key pathway important for cytoskeletal reorganization, in the EC-DG circuit leads to impairments in synaptic function and social recognition memory, and, importantly, optogenetic activation of the EC DG terminals reverses the social memory deficits in the transgenic mice. These results provide compelling evidence that activation of the EC-DG pathway underlies social recognition memory recall and that PAK signaling may play a critical role in modulating this process. PMID- 29791851 TI - Distinct Frequency Specialization for Detecting Dark Transients in Humans and Tree Shrews. AB - Despite well-known privileged perception of dark over light stimuli, it is unknown to what extent this dark dominance is maintained when visual transients occur in rapid succession, for example, during perception of moving stimuli. Here, we address this question using dark and light transients presented at different flicker frequencies. Although both human participants and tree shrews exhibited dark dominance for temporally modulated transients, these occurred at different flicker frequencies, namely, at 11 Hz in humans and 40 Hz and higher in tree shrews. Tree shrew V1 neuronal activity confirmed that differences between light and dark flicker were maximal at 40 Hz, corresponding closely to behavioral findings. These findings suggest large differences in flicker perception between humans and tree shrews, which may be related to the lifestyle of these species. A specialization for detecting dark transients at high temporal frequencies may thus be adaptive for tree shrews, which are particularly fast-moving small mammals. PMID- 29791850 TI - The Memory of Environmental Chemical Exposure in C. elegans Is Dependent on the Jumonji Demethylases jmjd-2 and jmjd-3/utx-1. AB - How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A in C. elegans. We show that Bisphenol A (BPA) exposure causes the derepression of an epigenomically silenced transgene in the germline for 5 generations, regardless of ancestral response. Chromatin immunoprecipitation sequencing (ChIP-seq), histone modification quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3, as well as with reproductive dysfunctions, including germline apoptosis and embryonic lethality. Furthermore, targeting of the Jumonji demethylases JMJD-2 and JMJD-3/UTX-1 restores H3K9me3 and H3K27me3 levels, respectively, and it fully alleviates the BPA-induced transgenerational effects. Together, our results demonstrate the central role of repressive histone modifications in the inheritance of reproductive defects elicited by a common environmental chemical exposure. PMID- 29791852 TI - Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina. AB - Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position. PMID- 29791853 TI - p27Kip1 Modulates Axonal Transport by Regulating alpha-Tubulin Acetyltransferase 1 Stability. AB - The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the alpha-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. PMID- 29791855 TI - Myocardial Angiopoietin-1 Controls Atrial Chamber Morphogenesis by Spatiotemporal Degradation of Cardiac Jelly. AB - The four-chamber structure of the mammalian heart is established during embryonic development. While key regulators for ventricular development are well studied, regulatory mechanisms for atrial chamber morphogenesis remain poorly understood. Here, we found that angiopoietin-1 (Angpt1), a vascular maturation factor, is highly and specifically expressed in atrial myocardium during heart development. Loss of myocardial Angpt1 in mouse embryo led to severe impairment in atrial chamber morphogenesis. We revealed that Angpt1 deficiency results in excessive deposition of cardiac jelly, which disturbs regulation of myocardial growth, thereby impairing maturation of atrial chambers. Mechanistically, myocardial Angpt1 activates endocardial Tie2 and positively regulates expression of ADAMTS proteases, which is crucial for proper degradation of cardiac jelly. Accordingly, loss of Tie2 also impairs ADAMTS-mediated degradation of cardiac jelly in atrium. Collectively, myocardial Angpt1/endocardial Tie2 signaling in atrium promotes spatiotemporal degradation of cardiac jelly during early cardiac development and is therefore indispensable for atrial chamber morphogenesis. PMID- 29791854 TI - Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells. AB - Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. Studies on a null mutation in mice previously revealed that Nup133 is essential for embryonic development but not for mouse embryonic stem cell (mESC) proliferation. Using single-pore detection and average NE fluorescence intensity, we find that Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. However, loss of Nup133 specifically perturbs the formation of the nuclear basket as manifested by the absence of Tpr in about half of the NPCs combined with altered dynamics of Nup153. We further demonstrate that its central domain mediates Nup133's role in assembling Tpr and Nup153 into a properly configured nuclear basket. Our findings thus revisit the role of the Y-complex in pore biogenesis and provide insights into the interplay between NPC scaffold architecture, nuclear basket assembly, and the generation of heterogeneity among NPCs. PMID- 29791856 TI - Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential. AB - Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4. Blood cells generated from arterial HE were more than 100-fold enriched in T cell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and beta-globin. Together, these findings provide an innovative strategy to aid in the generation of definitive lymphomyeloid progenitors and lymphoid cells from hPSCs for immunotherapy through enhancing arterial programming of HE. PMID- 29791857 TI - A Cytoplasmic Argonaute Protein Promotes the Inheritance of RNAi. AB - RNAi-elicited gene silencing is heritable and can persist for multiple generations after its initial induction in C. elegans. However, the mechanism by which parental-acquired trait-specific information from RNAi is inherited by the progenies is not fully understood. Here, we identified a cytoplasmic Argonaute protein, WAGO-4, necessary for the inheritance of RNAi. WAGO-4 exhibits asymmetrical translocation to the germline during early embryogenesis, accumulates at the perinuclear foci in the germline, and is required for the inheritance of exogenous RNAi targeting both germline- and soma-expressed genes. WAGO-4 binds to 22G-RNAs and their mRNA targets. Interestingly, WAGO-4-associated endogenous 22G-RNAs target the same cohort of germline genes as CSR-1 and contain untemplated addition of uracil at the 3' ends. The poly(U) polymerase CDE-1 is required for the untemplated uridylation of 22G-RNAs and inheritance of RNAi. Therefore, we conclude that, in addition to the nuclear RNAi pathway, the cytoplasmic RNAi machinery also promotes RNAi inheritance. PMID- 29791860 TI - The Olfactory Logic behind Fruit Odor Preferences in Larval and Adult Drosophila. AB - Despite the comprehensive knowledge on odor coding, our understanding of the relationship between sensory input and behavioral output in Drosophila remains weak. Here, we measure the behavioral responses generated by larval and adult flies in response to 34 fruit odors and find that larval preference for fruit odors differs from that of adult flies. Next, we provide a functional analysis of the full repertoire of the peripheral olfactory system using the same comprehensive stimulus spectrum. We find that 90% and 53% of larval and adult olfactory receptors tested here, respectively, are involved in evaluating these fruit odors. Finally, we find that the total amount of olfactory neuronal activity correlates strongly positively with behavioral output in larvae and correlates weakly negatively in adult flies. Our results suggest that larval and adult flies have evolved different mechanisms for detection and computation of fruit odors, mechanisms likely mirroring the different lifestyles of both developmental stages. PMID- 29791861 TI - Hyperglucagonemia Mitigates the Effect of Metformin on Glucose Production in Prediabetes. PMID- 29791859 TI - Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission. AB - Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report that combining NGN2 programming with SMAD and WNT inhibition generates human patterned induced neurons (hpiNs). Single-cell analyses showed that hpiN cultures contained cells along a developmental continuum, ranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene and exhibited greater functionality, including NMDAR-mediated synaptic transmission. We conclude that utilizing single-cell and reporter gene approaches for selecting successfully programmed cells for study will greatly enhance the utility of hpiNs and other programmed neuronal populations in the modeling of nervous system disorders. PMID- 29791858 TI - A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes. AB - Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease susceptible conditions. Integration of acquired omics dimensions suggested FARP1 as a candidate essential for podocyte function, which could be substantiated by genetic analysis in humans and knockdown experiments in zebrafish. This work exemplifies how the integration of multi-omics datasets can identify a framework of cell-type-specific features relevant for organ health and disease. PMID- 29791862 TI - Hormone-dependent breast cancer: Targeting autophagy and PI3K overcomes Exemestane-acquired resistance. AB - The leading cause of cancer death in women around the world is breast cancer. The aromatase inhibitors (AIs) are considered - as first-line treatment for estrogen receptor-positive (ER+) breast tumors, in postmenopausal women. Exemestane (Exe) is a powerful steroidal AI, however, despite its therapeutic success, Exe acquired resistance may occur leading to tumor relapse. Our group previously demonstrated that autophagy acts as a pro-survival process in Exe-induced cell death of ER+ sensitive breast cancer cells. In this work, the role of autophagy and its relationship with the PI3K/AKT/mTOR pathway in Exe-acquired resistance was explored. In that way, the mechanism behind the effects of the combination of Exe with pan-PI3K, or autophagic inhibitors, was studied in a long-term estrogen deprived ER+ breast cancer cell line (LTEDaro cells). Our results indicate that Exe induces autophagy as a cytoprotective mechanism linked to acquired resistance. Moreover, it was demonstrated that by inhibiting autophagy and/or PI3K pathway it is possible to revert Exe-resistance through apoptosis promotion, disruption of cell cycle, and inhibition of cell survival pathways. This work provides new insights into the mechanisms involved in Exe-acquired resistance, pointing autophagy as an attractive therapeutic target to surpass it. Thus, it highlights new targets that together with aromatase inhibition may improve ER+ breast cancer therapy, overcoming AIs-acquired resistance. PMID- 29791863 TI - Role of GW182 protein in the cell. AB - GW182 proteins interact directly with the argonaute proteins and constitute key components of miRNA repressor complexes (miRISC) in metazoans. As argonautes are insufficient for silencing they recruit the GW182 s that act as scaffold proteins inducing downstream translational repression, target mRNA deadenylation and exonucleolytic mRNA degradation. Besides their role as part of repressor complexes inside the cell, they function in wide variety of cellular processes as highlighted in this review. The present review summarises and discusses in detail our current knowledge of the GW182 s and their role inside the cell. PMID- 29791864 TI - LncRNA TUG1 interacting with miR-144 contributes to proliferation, migration and tumorigenesis through activating the JAK2/STAT3 pathway in hepatocellular carcinoma. AB - Recently, it is reported that taurine upregulated gene 1 (TUG1) participates in the tumor progression by acting as a competing endogenous RNA (ceRNA) of miRNAs. Nonetheless, whether TUG1 could serve as a ceRNA of miR-144 in hepatocellular carcinoma (HCC) progression remains undefined. Here, our results indicated that there was a marked rise in TUG1 expression in HCC tissues and cells, and downregulation of TUG1 hindered proliferation and migration of HCC cells. Additionally, TUG1 was validated to act as a molecular sponge of miR-144. Furthermore, we found that TUG1 interacting with miR-144 contributed to proliferation and migration of HCC cells via activating the JAK2/STAT3 pathway in vitro. Moreover, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-144 via inactivation of the JAK2/STAT3 pathway. In conclusion, TUG1 interacting with miR-144 contributed to proliferation, migration and tumorigenesis through activation of the JAK2/STAT3 pathway in HCC. PMID- 29791865 TI - Executive and arousal vigilance decrement in the context of the attentional networks: The ANTI-Vea task. AB - BACKGROUND: Vigilance is generally understood as the ability to detect infrequent critical events through long time periods. In tasks like the Sustained Attention to Response Task (SART), participants tend to detect fewer events across time, a phenomenon known as "vigilance decrement". However, vigilance might also involve sustaining a tonic arousal level. In the Psychomotor Vigilance Test (PVT), the vigilance decrement corresponds to an increment across time in both mean and variability of reaction time. NEW METHOD: The present study aimed to develop a single task -Attentional Networks Test for Interactions and Vigilance - executive and arousal components (ANTI-Vea)- to simultaneously assess both components of vigilance (i.e., the executive vigilance as in the SART, and the arousal vigilance as in the PVT), while measuring the classic attentional functions (phasic alertness, orienting, and executive control). RESULTS: In Experiment #1, the executive vigilance decrement was found as an increment in response bias. In Experiment #2, this result was replicated, and the arousal vigilance decrement was simultaneously observed as an increment in reaction time. COMPARISON WITH EXISTING METHOD: The ANTI-Vea solves some issues observed in the previous ANTI-V task with the executive vigilance measure (e.g., a low hit rate and no vigilance decrement). Furthermore, the new ANTI-Vea task assesses both components of vigilance together with others typical attentional functions. CONCLUSIONS: The new attentional networks test developed here may be useful to provide a better understanding of the human attentional system. The role of sensitivity and response bias in the executive vigilance decrement are discussed. PMID- 29791866 TI - 17 beta-Estradiol exacerbates methamphetamine-induced anxiety-like behavior in female mice. AB - The present experiment investigated the effect of 17 beta-estradiol (E2) on anxiety-like behavior following methamphetamine administration in female, Swiss Webster mice. Mice underwent bilateral ovariectomy (OVX) followed by a subcutaneous implantation of a Silastic capsule containing either sesame oil (OVX + Oil) or E2 (36 MUg/ml; OVX + E2). One week later, mice were placed in an open field chamber for an 8-h session. During the first 3 h of the session, mice were permitted to run in the absence of any drug (baseline). Then, mice were injected intraperitoneally with methamphetamine (0.25, 0.5 or 1.0 mg/kg) or vehicle (physiological saline) and returned to the open-field chamber for the remaining five hours of the session. Mice were injected with vehicle or a different methamphetamine dose once a week for 4 weeks. Four measures of anxiety were assessed: distanced traveled, vertical counts, time in the center, and time resting in the perimeter of the chamber. OVX + E2 were less active and spent less time in the center than OVX + Oil mice during Hour 1 at certain doses, but not during remaining baseline hours (Hours 2-3). Furthermore, group differences were not observed during the Stimulant Phase (Hour 4) following injection of any methamphetamine dose (0.25, 0.5 or 1.0 mg/kg) or the vehicle. However, OVX + E2 mice were less active, spent less time in the center, and spent more time resting in the perimeter of the chamber compared to OVX + Oil mice during certain hours of the Clearance Phase (Hours 5-8) following injection of the high (1.0 mg/kg), but not the low (0.25 mg/kg) or moderate (0.5 mg/kg), methamphetamine doses. These results suggest that E2 exacerbates anxiety-like behavior during acute clearance from a high methamphetamine dose in OVX female mice, perhaps indicating that E2 contributes to drug relapse in women by worsening anxiety-related withdrawal symptoms. PMID- 29791867 TI - Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review. AB - In addition to the burden of a life-threatening diagnosis, cancer patients are struggling with adverse side-effects from cancer treatment. Chemotherapy has been linked to an array of cognitive impairments and alterations in brain structure and function ("chemobrain"). In this review, we summarized the existing evidence that evaluate the changes in cognitive functioning and brain with chemotherapy, as assessed using structural and functional MRI-based techniques in a longitudinal design. This review followed the latest PRISMA guidelines using Embase, Medline, PsychINFO, Scopus, and Web of Science databases with date restrictions from 2012 to 2017. Fourteen research articles met the key inclusion criteria: (i) the studies involved adult cancer patients (mean age >= 18); (ii) the use of chemotherapy in the treatment of cancer; (iii) pre-post assessment of behavioral and brain-based outcomes; and (iv) abstracts written in English. Effect sizes of subjective and objective cognitive impairments from the reviewed studies were estimated using Cohen's d or z-scores. We calculated percentage of mean change or effect sizes for main neuroimaging findings when data were available. Strength of the correlations between brain alterations and cognitive changes was obtained using squared correlation coefficients. Small to medium effect sizes were shown? on individual tests of attention, processing speed, verbal memory, and executive control; and medium effect sizes on self-report questionnaires. Neuroimaging data showed reduced grey matter density in cancer patients in frontal, parietal, and temporal regions. Changes in brain function (brain activation and cerebral blood flow) were observed with cancer across functional networks involving (pre)frontal, parietal, occipital, temporal, and cerebellar regions. Data from diffusion-weighted MRI suggested reduced white matter integrity involving the superior longitudinal fasciculus, corpus callosum, forceps major, and corona radiate, and altered structural connectivity across the whole brain network. Finally, we observed moderate-to-strong correlations between worsening cognitive function and morphological changes in frontal brain regions. While MRI is a powerful tool for detection of longitudinal brain changes in the 'chemobrain', the underlying biological mechanisms are still unclear. Continued work in this field will hopefully detect MRI metrics to be used as biomarkers to help guide cognitive treatment at the individual cancer patient level. PMID- 29791869 TI - Ghrelin and the heart. AB - Ghrelin, a growth hormone-releasing peptide that was first discovered in the stomach of rats in 1999, is an endogenous ligand of growth hormone secretagogue receptor. Ghrelin exerts its potent growth hormone-releasing and orexigenic activities by binding to specific receptors in the brain. Subsequent studies showed that ghrelin participates in the regulation of diverse processes, including energy balance, body weight maintenance, and glucose and fat metabolism, and demonstrated that ghrelin is beneficial for treatment of cardiac diseases. In animal models of chronic heart failure, administration of ghrelin improves cardiac function and remodeling, and these findings were recapitulated in human patients with heart failure. Also in animal models, ghrelin administration effectively diminishes pulmonary hypertension induced by monocrotaline or chronic hypoxia. In addition, repeated administration of ghrelin to cachectic chronic obstructive pulmonary disease patients has positive effects on body composition, including amelioration of muscle wasting, improvement of functional capacity, and sympathetic activity. Moreover, administration of ghrelin early after myocardial infarction decreases the frequency of fatal arrhythmia and improved the survival rate. In ghrelin-deficient mice, both exogenous and endogenous ghrelin protects against fatal arrhythmia and promotes remodeling after myocardial infarction. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system have not been fully elucidated, some evidence suggests that its beneficial effects are mediated through both direct actions on cardiovascular cells and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiac disease. PMID- 29791868 TI - Ontogeny of white matter, toll-like receptor expression, and motor skills in the neonatal ferret. AB - Inflammation caused by perinatal infection, superimposed with hypoxia and/or hyperoxia, appears to be important in the pathogenesis of preterm neonatal encephalopathy, with white matter particularly vulnerable during the third trimester. The associated inflammatory response is at least partly mediated through Toll-like receptor (TLR)-dependent mechanisms. Immunohistochemistry, gene expression, and behavioral studies were used to characterize white matter development and determine TLR3 and TLR4 expression and accumulation in the neonatal ferret brain. Expression of markers of white matter development increased significantly between postnatal day (P)1 and P10 (NG2, PDGFRalpha) or P15 (Olig2), and either remained elevated (NG2), or decreased again at P40 (PDGFRalpha, Olig2). Olig2 immunostaining within the internal capsule was also greatest at P15. Myelin basic protein (MBP) immunostaining and mRNA expression increased markedly from P15 to P40 and into adulthood, which correlated with increasing performance on behavioral tests (negative geotaxis, cliff aversion, righting reflex, and catwalk gait analysis). TLR4 and TLR3 positive staining was low at all ages, but TLR3 and TLR4 mRNA expression both increased significantly from P1 to P40. Following lipopolysaccharide (LPS) and hypoxia/hyperoxia exposure at P10, meningeal and parenchymal inflammation was seen, including an increase in TLR4 positive cells. These data suggest that the neuroinflammation associated with prematurity could be modeled in the newborn ferret. PMID- 29791870 TI - MYC-induced metabolic stress and tumorigenesis. AB - The MYC oncogene is commonly altered across human cancers. Distinct from the normal MYC proto-oncogene, which is under tight transcriptional, translational, and post-translational control, deregulated oncogenic MYC drives imbalanced, non linear amplification of transcription that results in oncogenic 'stress.' The term 'stress' had been a euphemism for our lack of mechanistic understanding, but synthesis of many studies over the past decade provides a more coherent picture of oncogenic MYC driving metastable cellular states, particularly altered metabolism, that activate and depend on cellular stress response pathways to allow for continued growth and survival. Both deregulated metabolism and these stress response pathways represent vulnerabilities that can be exploited therapeutically. PMID- 29791871 TI - Network-Based Disease Module Discovery by a Novel Seed Connector Algorithm with Pathobiological Implications. AB - Understanding the genetic basis of complex diseases is challenging. Prior work shows that disease-related proteins do not typically function in isolation. Rather, they often interact with each other to form a network module that underlies dysfunctional mechanistic pathways. Identifying such disease modules will provide insights into a systems-level understanding of molecular mechanisms of diseases. Owing to the incompleteness of our knowledge of disease proteins and limited information on the biological mediators of pathobiological processes, the key proteins (seed proteins) for many diseases appear scattered over the human protein-protein interactome and form a few small branches, rather than coherent network modules. In this paper, we develop a network-based algorithm, called the Seed Connector algorithm (SCA), to pinpoint disease modules by adding as few additional linking proteins (seed connectors) to the seed protein pool as possible. Such seed connectors are hidden disease module elements that are critical for interpreting the functional context of disease proteins. The SCA aims to connect seed disease proteins so that disease mechanisms and pathways can be decoded based on predicted coherent network modules. We validate the algorithm using a large corpus of 70 complex diseases and binding targets of over 200 drugs, and demonstrate the biological relevance of the seed connectors. Lastly, as a specific proof of concept, we apply the SCA to a set of seed proteins for coronary artery disease derived from a meta-analysis of large-scale genome-wide association studies and obtain a coronary artery disease module enriched with important disease-related signaling pathways and drug targets not previously recognized. PMID- 29791873 TI - RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton. AB - The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rbeta, and the expression of PDGF-Rbeta in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rbeta inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction. In addition, PDGF-BB-mediated cell proliferation and migration were suppressed by PDGF-Rbeta inhibition, RhoA suppression, and ROCK inhibition, suggesting that PDGF-BB promotes phenotypic modulation of HA VSMCs by activating the RhoA/ROCK pathway via the PDGF receptor. Moreover, suppressing both ROCK1 and ROCK2 blocked cell cycle progression from G0/G1 to S phase by decreasing the transcription and protein expression of cyclin D1, CDK2, and CDK4 via JNK/c-Jun pathway, thus reducing cell proliferation in PDGF-BB treated HA-VSMCs. ROCK1 deletion, rather than ROCK2 suppression, significantly inhibited PDGF-BB-induced migration by reducing the expression of vimentin and preventing the remodeling of vimentin and phospho-vimentin. Furthermore, ROCK1 deletion suppressed vimentin by inhibiting the phosphorylation of Smad2/3 and the nuclear translocation of Smad4. These findings suggested that ROCK1 and ROCK2 might play different roles in PDGF-BB-mediated cell proliferation and migration in HA-VSMCs. In addition, PDGF-BB and its receptor participated in neointima formation and vascular remodeling by promoting cell cycle protein expression via the JNK pathway and enhancing vimentin expression in a rat balloon injury model; effects that were inhibited by treatment with fasudil. Together, the results of this study reveal a novel mechanism through which RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton. PMID- 29791872 TI - Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes. AB - Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development. PMID- 29791874 TI - Fabrication of electrospun poly(vinyl alcohol)/dextran nanofibers via emulsion process as drug delivery system: Kinetics and in vitro release study. AB - A green electrospinning was used for the fabrication of PVA/Dex (dextran sulfate) nanofibers as a carrier for drug delivery. Core-shell nanofibers were fabricated by emulsion electrospinning from PVA/Dex loaded with ciprofloxacin (Cipro) as a model drug. The ratio of the PVA/Dex mixture was optimized and nanofibers were stabilized against disintegration in water by thermal treatment at 120 degrees C. The morphology of the prepared nanofibers was observed by scanning electron microscopy (SEM) and the core-shell structure of the nanofibers was confirmed by transmission electron microscopy (TEM). Drug entrapment was confirmed by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The interaction between PVA and Dex was affirmed by differential scanning calorimetry (DSC). In vitro drug release was monitored by UV-vis spectrophotometer and its associated mechanism was studied using diverse kinetic models. The release study demonstrated that the core-shell nanofibers can sustain the Cipro release compared with the blending electrospinning nanofibers. Moreover, the drug release mechanism is controlled by the Dex content of the polymer blends and can occur by diffusion within the delivery system. It is anticipated that Cipro@PVA/Dex nanofibers are promising eco-friendly drug delivery system which can be prepared by a green method. PMID- 29791875 TI - Effects of potassium fertilization on potato starch physicochemical properties. AB - Potato starch serves as an excellent raw material or food additive in the food industry. With the advancement of the potato staple food strategy in China, improving the potato starch yield and quality has attracted more and more attention. Potassium is an essential nutrient for potato due to its direct effects on the yield and quality of potato tubers. Here, the effects of three different potassium levels on potato starch physicochemical properties were evaluated by field experiments. With increasing potassium fertilization rates, the amylose content, phosphorus content and particle size decreased, thereby resulting in low gelatinization temperature, breakdown and setback viscosity, and high swelling power, relative crystallinity and transparency. Our study indicated that enhanced potassium fertilization improved the resistance to heat and shear stress and decreased the retrogradation of starch, and the 270 kg/ha potassium fertilization rate could obtain the highest tuber and starch production with desirable starch physicochemical properties. The integrated results also provide some novel insights into the management of the fertilization conditions to obtain native starches with special properties. PMID- 29791876 TI - Extraction and characterization of cashew tree (Anacardium occidentale) gum; use in aceclofenac dental pastes. AB - In the current work, the usefulness of extracted cashew tree gum (CG) as pharmaceutical excipient in dental pastes containing aceclofenac (AC) for the pain management in the periodontitis treatment was investigated. CG was extracted from crude exudate of cashew tree (Anacardium occidentale, family: Anacardiaceae) (yield 19.22%). Physicochemical characteristics like colour, odour, taste, solubility, pH and viscosity of extracted CG were estimated; the phytochemical identification tests indicated the presence of carbohydrates and mucilage within it. It was also characterized by FTIR spectroscopy and 1H NMR analyses. Using the extracted CG (as natural mucoadhesive polymer) with calcium carbonate (abrasive agent), glycerin (humectant and cosolvent), methyl paraben (preservative), sodium lauryl sulfate (surfactant) and camphor (flavoring agent), 1% w/w AC dental pastes was formulated via conventional trituration. The drug contents, viscosities and pHs, tube extrudabilities and tube spreadabilities of these dental pastes were observed within permissible ranges. The dental pastes demonstrated sustained AC releasing over 6 h, in vitro and also revealed good adhesion to the oral mucosal membrane. These 1% w/w AC dental pastes can be used in the effectual management of dental inflammation and pain through local delivery of AC over a prolonged in the periodontitis treatment. PMID- 29791878 TI - Computational design of antibodies. AB - Antibody design aims to create new antibodies with biological activity that can be used in therapy and research. Traditional methods for antibody discovery, such as animal immunization and large-scale library screening, generate antibodies that bind to the target of interest, but do not necessarily have the desired functional effect. Computational methods can be utilized as a means to guide the search for biologically relevant antibodies, focusing on specificity and affinity determinants to target a particular region of the antigen. Such an approach would allow for the design of epitope-specific antibodies that will have the desired effect on the function of the targeted protein. PMID- 29791879 TI - Seizure imitators monitored using video-EEG in children with intellectual disabilities. AB - Diagnosis of seizure imitators in children is often challenging, and individuals with intellectual disability (ID) could be at additional risk of seizure imitator misdiagnosis. We aimed to elucidate distinct features of clinical semiology among children of different intellectual levels, which may help in distinguishing seizure imitators from epilepsy in such individuals. We retrospectively compared semiological features of seizure imitators in children with and without ID captured using video-electroencephalography (video-EEG). Seizure imitators were classified based on the definition of the International League Against Epilepsy (ILAE). A total of 67 individuals (mean age: 8.4 years, SD: 4.2 years) with seizure imitators documented using long-term video-EEG were identified, in which 27 patients had normal IQ/DQ, 20 had moderate ID, and 20 had severe ID. There was no statistically significant difference in the semiological features of seizure imitators between individuals with ID and those without ID; similarly, no difference was found between those with moderate ID and severe ID compared with individuals with normal IQ/DQ. Among all the patients, altered responsiveness mimicking cognitive or absence seizures was most frequently observed (36%), followed by jerks mimicking myoclonic seizures (22%). The most common seizure imitators among all the patients were unclassifiable nonepileptic seizures per the ILAE definition (28 cases, 42%), followed by day dreaming (24 cases, 36%) and physiological myoclonus (14 cases, 21%). In summary, the present study found no marked difference in semiological features of seizure imitators between patients with ID and those without ID regardless of ID severity, suggesting the necessity of early video-EEG for correct diagnosis. PMID- 29791877 TI - Enzyme-assisted extraction, chemical characteristics, and immunostimulatory activity of polysaccharides from Korean ginseng (Panax ginseng Meyer). AB - In this study, enzyme-assisted extraction was used to isolate functional polysaccharides from Korean ginseng (Panax ginseng Meyer) and the physicochemical and biological properties of the extracted polysaccharides were investigated, comparing with those from traditional hot-water extraction (FGWP). In macrophages, their effects on cytokines production could be ordered as FGEP-CA >= FGEP-A > FGEP-C > FGWP, suggesting that FGEP-CA (combined cellulase- and alpha amylase-extracted polysaccharide) is a potent immunostimulator. In addition, enzymatic digestion led to differences in the monosaccharide profile of the extract. FGWP mainly consisted of rhamnose, arabinose, galactose, galacturonic acid, and glucose in molar percentages of 1.8:10.1:9.2:17.8:60.6, whereas FGEP-CA was 3.2:11.4:16.5:22.3:45.8, respectively, suggesting that enzyme-assisted extraction of ginseng polysaccharides produces a higher proportion of pectin polysaccharides. The HPLC profile of FGEP-CA also showed lower and more heterogeneous molecular weights than FGWP did. In cyclophosphamide-induced immunosuppressed mice, FGEP-CA administration ameliorated decreased spleen and thymus indices (200 mg/kg), lymphocyte proliferation, natural killer cell activity, leukocyte counts, and the serum cytokines, interleukin-2, interleukin 6, and interferon-gamma (100 and 200 mg/kg). These results suggest that enzyme assisted extraction using cellulase and alpha-amylase is an effective method for the preparation of functional polysaccharides from fresh Korean ginseng, and FGEP CA could be utilized as a potential immune-stimulatory agent. PMID- 29791880 TI - Dietary cadmium intake from rice and vegetables and potential health risk: A case study in Xiangtan, southern China. AB - Soil contamination in some areas of southern China has resulted in elevated dietary intake of cadmium (Cd), posing a potential risk to human health. A survey of paired soil-rice (n = 200) and soil-vegetable (n = 142) samples was conducted in Xiangtan county of Hunan province, southern China. The concentrations of Cd in all the samples were determined by inductively coupled plasma mass spectrometry. Dietary intakes of Cd from the consumption of locally produced rice and vegetables were estimated for different age groups. Among the 342 crop samples collected in the survey, 88% and 29% of rice grain and vegetable samples, respectively, exceeded the Chinese maximum permissible limit for Cd (0.2 mg dry weight kg-1, 0.2 mg fresh weight kg-1 and 0.1 mg fresh weight kg-1 for rice, leafy vegetables and for rootstalk and legume vegetables, respectively). The median dietary Cd intake varied from 66.5 to 116 MUg Cd kg-1 body weight (BW) month-1, with children (4-11 years) exhibiting the highest intake. These values are 2.7-4.6 times the tolerable dietary intake of 25 MUg kg-1 BW month-1 recommended by the Joint FAO/WHO Expert Committee on Food Additives. For the general population in Xiangtan county, rice contributed the majority (81%) of the Cd intake with vegetables contributing only 19%. The median hazard quotient calculated from dietary Cd intake was 2.4 times the permissible level, indicating a high risk to the local residents. This study highlights an urgent need to reduce the transfer of Cd from soil to the food chain in the investigated region. PMID- 29791882 TI - Simulation-based assessment of the impact of fertiliser and herbicide application on freshwater ecosystems at the Three Gorges Reservoir in China. AB - Dams have profound impacts on river ecosystems, amongst them inundation of land, altered dynamics of the water body or uprising reservoir backwaters influencing tributary or upstream river sections. Along the outstandingly ecologically important Yangtze River in China, the Three Gorges Reservoir (TGR) is the largest project, covering an area of 1080 km2. From the beginning, the dam-project came in for criticism on increasing environmental risks due to sub-merging former industrial and urban areas. We simulated dynamics of biotic and abiotic components of the TGR ecosystem (trophic guilds of aquatic organisms, hydrodynamics, nutrients), as well as the behaviour of the herbicidal substance propanil and its metabolites 3,4-Dichloroaniline (DCA) and 3,3',4,4' tetrachloroazoxybenzene (TCAB). A modelling environment, provided by the AQUATOX software, was adapted to the specific situation at a tributary reach to the Yangtze river 'Daning River'. As the simulated food web contained several interconnected trophic levels, a significant biomagnification of metabolites was demonstrated by our simulation studies. In particular, newly emerging stagnant downstream sections of tributaries exhibited high probabilities due to accumulating pesticides from upstream sources. The common problem of algal blooms in the TGR-region was addressed by dose-response simulation experiments with essential nutrients. Impacts on structure and abundance of populations of aquatic organisms were shown. However, even high nutrient loads resulted in only slight changes of densities of organisms of all trophic levels. Nevertheless, the probabilities for large-scale algal blooms affecting drinking water quality were considered low because of high flow velocities and discharge rates towards the Yangtze River. We see high potential of simulation-based assessments that provide information for risk managers dealing with whole catchment areas. They are put in the position to differentiate the magnitude of impacts of various factors and decide about the most effective remediation measures. PMID- 29791881 TI - Effect of methane partial pressure on the performance of a membrane biofilm reactor coupling methane-dependent denitrification and anammox. AB - Complete nitrogen removal has recently been demonstrated by integrating anaerobic ammonium oxidation (anammox) and denitrifying anaerobic methane oxidation (DAMO) processes. In this work, the effect of methane partial pressure on the performance of a membrane biofilm reactor (MBfR) consisting of DAMO and anammox microorganisms was evaluated. The activities of DAMO archaea and DAMO bacteria in the biofilm increased significantly with increased methane partial pressure, from 367 +/- 9 and 58 +/- 22 mg-N L-1d-1 to 580 +/- 12 and 222 +/- 22 mg-N L-1d-1, respectively, while the activity of anammox bacteria only increased slightly, when the methane partial pressure was elevated from 0.24 to 1.39 atm in the short term batch tests. The results were supported by a long-term (seven weeks) continuous test, when the methane partial pressure was dropped from 1.39 to 0.78 atm. The methane utilization efficiency was always above 96% during both short term and long-term tests. Taken together, nitrogen removal rate (especially the nitrate reduction rate by DAMO archaea) and methane utilization efficiency could be maintained at high levels in a broad range of methane partial pressure (0.24 1.39 atm in this study). In addition, a previously established DAMO/anammox biofilm model was used to analyze the experimental data. The observed impacts of methane partial pressure on biofilm activity were well explained by the modeling results. These results suggest that methane partial pressure can potentially be used as a manipulated variable to control reaction rates, ultimately to maintain high nitrogen removal efficiency, according to nitrogen loading rate. PMID- 29791883 TI - Relationship between modification of activated sludge wastewater treatment and changes in antibiotic resistance of bacteria. AB - Biological treatment processes at wastewater treatment plants (WWTPs), which are the most common methods of sewage treatment, could cause selective elimination and/or changes in the proportions of phenotypes/genotypes within bacterial populations in effluent. Therefore, WWTPs based on activated sludge used in sewage treatment constitute an important reservoir of enteric bacteria which harbour potentially transferable resistance genes. Together with treated wastewater, these microorganisms can penetrate the soil, surface water, rural groundwater supplies and drinking water. Because of this, the aim of this study was to determine the impact of various modification of sewage treatment (the conventional anaerobic/anoxic/oxic (A2/O) process, mechanical-biological (MB) system, sequencing batch reactors (SBR), mechanical-biological system with elevated removal of nutrients (MB-ERN)) on the amount of antibiotic resistant bacteria (ARB) (including E. coli) and antibiotic resistance genes (ARGs) in sewage flowing out of the 13 treatment plants using activated sludge technology. There were no significant differences in ARB and ARGs regardless of time of sampling and type of treated wastewater (p > 0.05). The highest percentage of reduction (up to 99.9%) in the amount of ARB and ARGs was observed in WWTPs with MB and MB-ERN systems. The lowest reduction was detected in WWTPs with SBR. A significant increase (p < 0.05) in the percentage of bacteria resistant to the new generation antibiotics (CTX and DOX) in total counts of microorganisms was observed in effluents (EFF) from WWTPs with A2/O system and with SBR. Among all ARGs analyzed, the highest prevalence of ARGs copies in EFF samples was observed for sul1, tet(A) and qepA, the lowest for blaTEM and blaSHV. Although, the results of presented study demonstrate high efficiency of ARB and ARGs removal during the wastewater treatment processes, especially by WWTPs with MB and MB-ERN systems, EFF is still an important reservoir of ARGs which can be transferred to other microorganisms. PMID- 29791884 TI - Rainfall as primary driver of discharge and solute export from rock glaciers: The Col d'Olen Rock Glacier in the NW Italian Alps. AB - Three hypotheses exist to explain how meteorological variables drive the amount and concentration of solute-enriched water from rock glaciers: (1) Warm periods cause increased subsurface ice melt, which releases solutes; (2) rain periods and the melt of long-lasting snow enhance dilution of rock-glacier outflows; and (3) percolation of rain through rock glaciers facilitates the export of solutes, causing an opposite effect as that described in hypothesis (2). This lack of detailed understanding likely exists because suitable studies of meteorological variables, hydrologic processes and chemical characteristics of water bodies downstream from rock glaciers are unavailable. In this study, a rock-glacier pond in the North-Western Italian Alps was studied on a weekly basis for the ice-free seasons 2014 and 2015 by observing the meteorological variables (air temperature, snowmelt, rainfall) assumed to drive the export of solute-enriched waters from the rock glacier and the hydrochemical response of the pond (water temperature as a proxy of rock-glacier discharge, stable water isotopes, major ions and selected trace elements). An intra-seasonal pattern of increasing solute export associated with higher rock-glacier discharge was found. Specifically, rainfall, after the winter snowpack depletion and prolonged periods of atmospheric temperature above 0 degrees C, was found to be the primary driver of solute export from the rock glacier during the ice-free season. This occurs likely through the flushing of isotopically- and geochemically-enriched icemelt, causing concomitant increases in the rock-glacier discharge and the solute export (SO42-, Mg2+, Ca2+, Ni, Mn, Co). Moreover, flushing of microbially-active sediments can cause increases in NO3- export. PMID- 29791885 TI - Multi-barrier approach for removing organic micropollutants using mobile water treatment systems. AB - The diversity of organic micropollutants (OMPs) in aquatic environments has been increasing rapidly during the last decade. Therefore, it is important to monitor and attenuate emerging contaminants before they can negatively affect the aquatic environment. However, due to the diversity and complexity of OMPs, there are limitations to using a single method for treating a combination of these pollutants. To address this issue, a mobile water treatment system (MWTS) equipped with different treatment units was designed to remove OMPs under field conditions. The MWTS was configured with various modular units including coagulation, flocculation, dissolved air flotation, membrane filtration, ozone oxidation, granular activated carbon, and UV disinfection. Each treatment unit could be operated either individually or in different combinations to identify the optimal configuration of treatment units for the removal of OMPs. To investigate the effectiveness of the MWTS, twelve OMPs were selected and introduced simultaneously into the feed water samples collected from different rivers throughout Korea. The current study proved that the MTWS is an effective solution to treat OMPs and is a time saving treatment system. The combined effects of the different treatment units removed over 99% of the selected OMPs, regardless of their physicochemical properties. Moreover, since the system is mobile, on-site analyses can be conducted to identify the most effective treatment method and configuration for each OMP. PMID- 29791886 TI - The emission of BTEX compounds during movement of passenger car in accordance with the NEDC. AB - The results of the research in the field of benzene, toluene, ethylbenzene and xylene isomers (BTEX) concentrations in exhaust gases of spark ignition engines under different operating conditions are presented in this paper. The aim of this paper is to gain a clearer insight into the impact of different engine working parameters on the concentrations of BTEX. The experimental investigation has been performed on the SCHENCK 230 W test stand with the controlled IC engine. The engine operating points have been chosen based on the results of a simulation and they are considered as the typical driving conditions according to the New European Driving Cycle. Concentration levels of BTEX compounds in exhaust gas mixtures have been determined by gas chromatography technique by using the combination of Supelcowax 10-Polyethylene glycol column and the PID detector. Based on the experimental research results, the emission model of BTEX compounds has been defined by the simulation of movement of a Fiat Punto Classic passenger car in accordance with the NEDC cycle. Using the results obtained within the simulation, the official statistics on the number of gasoline-powered cars on the territory of the Republic of Serbia and the European Commission data on the annual distance traveled by car, the amounts of BTEX compounds emitted annually per car have been estimated, as well as the emissions of the entire Serbian car fleet. PMID- 29791887 TI - Long-term no-tillage application increases soil organic carbon, nitrous oxide emissions and faba bean (Vicia faba L.) yields under rain-fed Mediterranean conditions. AB - The introduction of legumes into crop sequences and the reduction of tillage intensity are both proposed as agronomic practices to mitigate the soil degradation and negative impact of agriculture on the environment. However, the joint effects of these practices on nitrous oxide (N2O) and ammonia (NH3) emissions from soil remain unclear, particularly concerning semiarid Mediterranean areas. In the frame of a long-term field experiment (23 years), a 2 year study was performed on the faba bean (Vicia faba L.) to evaluate the effects of the long-term use of no tillage (NT) compared to conventional tillage (CT) on yield and N2O and NH3 emissions from a Vertisol in a semiarid Mediterranean environment. Changes induced by the tillage system in soil bulk density, water filled pore space (WFPS), organic carbon (TOC) and total nitrogen (TN), denitrifying enzyme activity (DEA), and bacterial gene (16S, amoA, and nosZ) abundance were measured as parameters potentially affecting N gas emissions. No tillage, compared with CT, significantly increased the faba bean grain yield by 23%. The tillage system had no significant effect on soil NH3 emissions. Total N2O emissions, averaged over two cropping seasons, were higher in NT than those in CT plots (2.58 vs 1.71 kg N2O-N ha-1, respectively; P < 0.01). In addition, DEA was higher in NT compared to that in CT (74.6 vs 18.6 MUg N2O-N kg-1 h-1; P < 0.01). The higher N2O emissions in NT plots were ascribed to the increase of soil bulk density and WFPS, bacteria (16S abundance was 96% higher in NT than that in CT) and N cycle genes (amoA and nosZ abundances were respectively 154% and 84% higher in NT than that in CT). The total N2O emissions in faba bean were similar to those measured in other N-fertilized crops. In conclusion, a full evaluation of NT technique, besides the benefits on soil characteristics (e.g. TOC increase) and crop yield, must take into account some criticisms related to the increase of N2O emissions compared to CT. PMID- 29791888 TI - Boosted nutritional quality of food by CO2 enrichment fails to offset energy demand of herbivores under ocean warming, causing energy depletion and mortality. AB - The CO2-boosted trophic transfer from primary producers to herbivores has been increasingly discovered at natural CO2 vents and in laboratory experiments. Despite the emerging knowledge of this boosting effect, we do not know the extent to which it may be enhanced or dampened by ocean warming. We investigated whether ocean acidification and warming enhance the nutritional quality (C:N ratio) and energy content of turf algae, which is speculated to drive higher feeding rate, greater energy budget and eventually faster growth of herbivores. This proposal was tested by observing the physiological (feeding rate, respiration rate and energy budget) and demographic responses (growth and survival) of a common grazing gastropod (Phasianella australis) to ocean acidification and warming in a 6-month mesocosm experiment. Whilst we observed the boosting effect of ocean acidification and warming in isolation on the energy budget of herbivores by either increasing feeding rate on the more nutritious algae or increasing energy gain per feeding effort, their growth and survival were reduced by the sublethal thermal stress under ocean warming, especially when both climate change stressors were combined. This reduced growth and survival occurred as a consequence of depleted energy reserves, suggesting that the boosting effect via trophic transfer might not sufficiently compensate for the increased energy demand imposed by ocean warming. In circumstances where ocean acidification and warming create an energy demand on herbivores that outweighs the energy enhancement of their food (i.e. primary producers), the performance of herbivores to control their blooming resources likely deteriorates and thus runaway primary production ensues. PMID- 29791889 TI - A straightforward method for measuring the range of apparent density of microplastics. AB - Density of microplastics has been regarded as the primary property that affect the distribution and bioavailability of microplastics in the water column. For measuring the density of microplastis, we developed a simple and rapid method based on density gradient solutions. In this study, we tested four solvents to make the density gradient solutions, i.e., ethanol (0.8 g/cm3), ultrapure water (1.0 g/cm3), saturated NaI (1.8 g/cm3) and ZnCl2 (1.8 g/cm3). Density of microplastics was measured via observing the float or sink status in the density gradient solutions. We found that density gradient solutions made from ZnCl2 had a larger uncertainty in measuring density than that from NaI, most likely due to a higher surface tension of ZnCl2 solution. Solutions made from ethanol, ultrapure water, and NaI showed consistent density results with listed densities of commercial products, indicating that these density gradient solutions were suitable for measuring microplastics with a density range of 0.8-1.8 g/cm3. PMID- 29791890 TI - A robust and non-invertible fingerprint template for fingerprint matching system. AB - Fingerprint Recognition System is widely deployed in variety of application domain, ranging from forensic to mobile phones. Its widespread deployment in various applications were person authentication are required, has caused concern that a leaked fingerprint template may be used to reconstruct the original fingerprint and the reconstructed fingerprint can be used to circumvent all the applications the person is enrolled. In this paper, a non-invertible fingerprint template that stores only the relative geometric information about the minutiae points is proposed. The spatial location of the minutiae points in original fingerprint and its orientations are not available in the proposed template which makes it impossible to estimate the orientation of fingerprint from the template. The proposed template is invariant to rotation, translation and distortion and immune to reconstruction algorithm. The proposed system is experimented using standard FVC2000 database and yields better results in terms of EER and FMR as compared with latest techniques. PMID- 29791891 TI - Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma. AB - AIM: Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. METHODS: In this retrospective multicenter, observational cohort study, outcome after TEM only (n = 41) and completion surgery (n = 40) following TEM for a pT2-3 rectal adenocarcinoma was compared. RESULTS: Median follow-up was 29 months for the TEM only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. CONCLUSIONS: Although local recurrence after TEM-only for pT2-3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended. PMID- 29791893 TI - Reply to the Letter by Dr. Antonio Ponzetto Regarding "The Role of History of Gastro-Duodenal Ulcer in Patients with Upper Gastrointestinal Bleeding". PMID- 29791892 TI - Containing the Costs of Recurrent Gastro-Duodenal Ulcer Bleeding. PMID- 29791894 TI - Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells. AB - BACKGROUND/AIMS: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. METHODS: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. RESULTS: Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. CONCLUSION: Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells. PMID- 29791895 TI - Effect of Postprandial Administration of Esomeprazole on Reflux Symptoms in Gastroesophageal Reflux Disease: A Randomized, Controlled Trial. AB - BACKGROUND: Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD). METHODS: Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36). RESULTS: Thirty-two patients (17 [53.1%] men, aged 53.5 +/- 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Delta9.0 +/- 7.2 vs. Delta10.0 +/- 8.1, p = 0.29; Delta6.6 +/- 6.8 vs. Delta10.2 +/- 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Delta10.7 +/- 10.5 vs. Delta10.0 +/- 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period. CONCLUSION: Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals. PMID- 29791896 TI - Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation. AB - BACKGROUND: Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). METHODS: Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. RESULTS: By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 +/- 44 um) and high CtPo (60.3 +/- 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. CONCLUSIONS: Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD. PMID- 29791897 TI - Cutis Marmorata Telangiectatica Congenita Presenting as a Fetal Hemothorax. AB - We report a case of a fetus diagnosed at 28 weeks' gestation with a spontaneous prenatal hemothorax. Fetal intervention consisted of 2 thoracenteses with analysis of the pleural effusion. The pregnancy was further complicated by recurrence of the hemothorax, with subsequent mediastinal shift, hydrops, and nonreassuring antenatal testing requiring delivery at 31 weeks' gestation. Postnatal workup established the diagnoses of cutis marmorata telangiectatica congenita (CMTC) and pulmonary lymphangiectasia. The child is currently 4 years old and without any active medical issues or sequelae from the CMTC, pulmonary lymphangiectasia, or prenatal interventions. PMID- 29791898 TI - Intraoperative Analgesic Regimen and Cholecystectomy: A Closer Look. PMID- 29791899 TI - National Practice Patterns for Prenatal Monitoring in Gastroschisis: Gastroschisis Outcomes of Delivery (GOOD) Provider Survey. AB - BACKGROUND: Gastroschisis is an abdominal wall defect with increasing incidence. Given the lack of surveillance guidelines among maternal-fetal medicine (MFM) specialists, this study describes current practices in gastroschisis management. MATERIALS AND METHODS: An online survey was administered to MFM specialists from institutions affiliated with the North American Fetal Therapy Network (NAFTNet). Questions focused on surveillance timing, testing, findings that changed clinical management, and delivery plan. RESULTS: Responses were obtained from 29/29 (100%) NAFTNet centers, comprising 143/371 (39%) providers. The majority had a regimen for antenatal surveillance in patients with stable gastroschisis (94%; 134/141). Antenatal testing began at 32 weeks for 68% (89/131) of MFM specialists. The nonstress test (55%; 72/129), biophysical profile (50%; 63/126), and amniotic fluid index (64%; 84/131) were used weekly. Estimated fetal weight (EFW) was performed monthly by 79% (103/131) of providers. At 28 weeks, abnormal EFW (77%; 97/126) and Doppler ultrasound (78%; 99/127) most frequently altered management. In stable gastroschisis, 43% (60/140) of providers delivered at 37 weeks, and 29% (40/ 140) at 39 weeks. DISCUSSION: Gastroschisis management differs among NAFTNet centers, although the majority initiate surveillance at 32 weeks. Timing of delivery still requires consensus. Prospective studies are necessary to further optimize practice guidelines and patient care. PMID- 29791900 TI - Re-Operative Pancreaticoduodenectomy: Challenges and Outcomes. AB - BACKGROUND: Tata Memorial Centre (TMC) is a high-volume centre for pancreatic tumour resections. We found a continually increasing referral of pancreatic tumours for re-evaluation for surgery, after an initial unsuccessful attempt at resection. AIM: To evaluate reasons of initial in-operability, the feasibility of re-operative pancreatico-duodenectomy (R-PD) and short- and long-term outcomes after R-PD. METHODS: Data was collected from a prospective database of GI and hepato-pancreato-biliary service, TMC, Mumbai from January 2008 to December 2016. RESULTS: Forty patients with periampullary/pancreatic head tumours were referred to us after exploration. Thirty were planned for re-exploration, of whom 25 patients underwent successful R-PD, either upfront (n = 12) or after neo-adjuvant therapy (n = 13). Twenty were adenocarcinomas, 5 had other histologies. Majority of the patients were deemed inoperable in view of suspected vascular involvement at the time of initial surgery (68%). R0 resection was achieved in 90% of adenocarcinoma cases (n = 18). Postoperative major morbidity was 20% and mortality was 4% (n = 1). The estimated 1-, 2- and 5-year survival for those with adenocarcinoma was 83, 71.2, and 29.9% respectively. CONCLUSION: R-PD is safe and should be performed in experienced centres and can achieve long-term outcomes, comparable to conventional PD. The most common reason for denying resection at initial surgery was suspected or perceived vascular involvement. PMID- 29791901 TI - Exeunt Lateral Decubitus Radiographs. PMID- 29791902 TI - The Molecular Pathology of Myelodysplastic Syndrome. AB - The diagnosis and classification of myelodysplastic syndromes (MDS) are based on cytomorphology and cytogenetics (WHO classification). Prognosis is best defined by the Revised International Prognostic Scoring System (IPSS-R). In recent years, an increasing number of molecular aberrations have been discovered. They are already included in the classification (e.g., SF3B1) and, more importantly, have emerged as valuable markers for better classification, particularly for defining risk groups. Mutations in genes such as SF3B1 and IDH1/2 have already had an impact on targeted treatment approaches in MDS. PMID- 29791904 TI - The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against Mycobacterium tuberculosis Infection. AB - Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo. In DCs, this adaptor molecule was important for Ifn-beta expression and IL-12 production as well as for the surface expression of the activation markers CD40 and CD86. We also documented that Mtb DNA induces STING activation in murine fibroblasts. In vivo Mtb aerogenic infection induced the upregulation of the STING and cGAS (cyclic GMP-AMP synthase) genes, and Ifn-beta pulmonary expression was dependent on both sensors. However, mice deficient for STING or cGAS presented a similar outcome to wild type controls, with no major alterations in body weight gain, bacterial burden, or survival. Lung inflammation, proinflammatory cytokine production, and inflammatory cell recruitment were similar in STING- and cGAS-deficient mice compared to wild-type controls. In summary, although the STING pathway seems to be crucial for DC activation during Mtb infection, it is dispensable for host protection in vivo. PMID- 29791905 TI - Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study. AB - BACKGROUND: Chronic kidney disease (CKD) imposes a substantial burden on health care systems. There are some especially vulnerable groups with a high CKD burden, one of which is women. We performed an analysis of gender disparities in the prevalence of all CKD stages and renal replacement therapy (defined as impaired kidney function [IKF]) in 195 countries. METHODS: We used estimates produced by the Global Burden of Disease (GBD) Study 2016 revision using a Bayesian regression analytic tool, DisMoD-MR 2.1. Data on gross domestic product based on purchasing power parity per capita (GDP PPP) was obtained via the World Bank International Comparison Program database. To estimate gender disparities, we calculated the male:female all-age prevalence rate ratio for each IKF condition. RESULTS: In 2016, the global number of individuals with IKF reached 752.7 million, including 417.0 million females and 335.7 million males. The most prevalent form of IKF in both groups was albuminuria with preserved glomerular filtration rate. Geospatial analysis shows a very heterogeneous distribution of the male:female ratio for all IKF conditions, with the most prominent contrast found in kidney transplant patients. The median male:female ratio varies substantially according to GDP PPP quintiles; however, countries with different economic states could have similar male:female ratios. A strong correlation of GDP PPP with dialysis-to-transplant ratio was found. CONCLUSIONS: The GBD study highlights the prominent gender disparities in CKD prevalence among 195 countries. The nature of these disparities, however, is complex and must be interpreted cautiously taking into account all possible circumstances. PMID- 29791903 TI - A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression. AB - In mucosal inflammatory disorders, the protective influence of heme oxygenase-1 (HO-1) and its metabolic byproducts, carbon monoxide (CO) and biliverdin, is a topic of significant interest. Mechanisms under investigation include the regulation of macrophage function and mucosal cytokine expression. While there is an increasing recognition of the importance of epithelial-derived factors in the maintenance of intestinal mucosal homeostasis, the contribution of intestinal epithelial cell (IEC) HO-1 on inflammatory responses has not previously been investigated. We examined the influence of modulating HO-1 expression on the inflammatory response of human IECs. Engineered deficiency of HO-1 in Caco-2 and T84 IECs led to increased proinflammatory chemokine expression in response to pathogenic bacteria and inflammatory cytokine stimulation. Crosstalk with activated leukocytes also led to increased chemokine expression in HO-1-deficient cells in an IL-1beta dependent manner. Treatment of Caco-2 cells with a pharmacological inducer of HO-1 led to the inhibition of chemokine expression. Mechanistic studies suggest that HO-1 and HO-1-related transcription factors, but not HO-1 metabolic products, are partly responsible for the influence of HO-1 on chemokine expression. In conclusion, our data identify HO-1 as a central regulator of IEC chemokine expression that may contribute to homeo-stasis in the intestinal mucosa. PMID- 29791906 TI - Comparison of the Thermal Spread of Three Different Electrosurgical Generators on Rat Uterus: A Preliminary Experimental Study. AB - BACKGROUND/AIMS: The objective of this study was to compare the depth and width of thermal spread caused on rat uterine tissue after application of 3 different electrosurgical generators. METHODS: Alsa Excell 350 MCDSe (Unit A), Meditom DT 400P (Unit M), and ERBE Erbotom VIO 300 D (Unit E) electrosurgical units (ESUs) were used. The number of Wistar Hannover rats required to obtain valid results was 10. The primary objective of the study was to compare the 3 ESUs using the same instrument and the same waveform. The secondary objective of the study was to compare the differences between monopolar and bipolar systems of each ESU separately using the same waveform. RESULTS: The thermal spread caused by each ESU using monopolar instruments with continuous and interrupted waveforms was significantly different. Among the 3 devices, Unit A caused the largest thermal uterine tissue spread. On the other hand, Unit E caused the most superficial thermal tissue spread, and the smallest thermal spread among all ESUs. CONCLUSIONS: Surgeons should note that different ESUs used with the same power output might create different thermal effects especially in the monopolar configuration within the same waveform, for the same duration, and with the same instrument. PMID- 29791907 TI - Toll-Like Receptor 3 Signaling Contributes to Regional Neutrophil Recruitment in Cultured Human Glomerular Endothelial Cells. AB - BACKGROUND: Given the importance of neutrophil recruitment in the pathogenesis of glomerulonephritis (GN), the representative neutrophil chemoattractant C-X-C motif chemokine 1 (CXCL1)/GROalpha and the adhesion molecule E-selectin in glomerular endothelial cells (GECs) play a pivotal role in the development of GN. Endothelial Toll-like receptor 3 (TLR3) is thought to be involved in the inflammatory response via innate immunity. However, the role of endothelial TLR3 signaling in the expression of neutrophil chemoattractants and adhesion molecules remains to be elucidated. Thus, we aimed to examine this issue. METHODS: We treated normal human GECs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expressions of CXCL1 and E selectin using quantitative real-time reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against TLR3, interferon (IFN)-beta, nuclear factor (NF)-kappaB p65, and IFN regulatory factor (IRF) 3. We also used immunofluorescence to examine the endothelial expression of CXCL1 in biopsy specimens from patients with crescentic and non-crescentic purpura nephritis (PN). RESULTS: We found that the activation of TLR3 induced the endothelial expression of CXCL1 and E-selectin, and that this involved TLR3, -NF-kappaB, IRF3, and IFN-beta. Intense endothelial CXCL1 expression was observed in biopsy specimens from patients with crescentic PN. CONCLUSION: These findings support a role for glomerular antiviral innate immunity in the pathogenesis of GN. Intervention of glomerular TLR3 signaling may therefore be a suitable therapeutic strategy for treating GN in the future. PMID- 29791908 TI - A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia. AB - Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations. PMID- 29791909 TI - Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine. AB - BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss. PMID- 29791910 TI - Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus. AB - OBJECTIVE/AIM: Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats. METHODS: In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment - group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis. RESULTS: Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001). CONCLUSION: The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials. PMID- 29791911 TI - Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury. AB - BACKGROUND: Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. SUMMARY: Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success. PMID- 29791912 TI - Differential Expression of MicroRNAs in Breast Cancers from Four Different Ethnicities. AB - INTRODUCTION: Breast cancer outcomes vary across different ethnic groups. MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression across a range of pathologies, including breast cancer. The aim of this study was to evaluate the presence and expression of miRs in breast cancer samples from different ethnic groups. MATERIALS AND METHODS: Breast cancer tissue from 4 ethnic groups, i.e., British Caucasian, British Black, Nigerian, and Indian, were identified and matched for patients' age, tumour grade/type, and 10 * 10 um sections taken. Tumour areas were macrodissected, total RNA was extracted, and cDNA was synthesised. cDNA was applied to human miScript PCR arrays allowing the quantification of 84 of the most abundantly expressed/best-characterised miRs. RESULTS: Differential expression of 9 miRs was seen across the 4 groups. Significantly higher levels of miR-140-5p, miR-194 and miR-423-5p (the last of which harbours the single-nucleotide polymorphism rs6505162) were seen in the breast tumours of Nigerian patients when compared with other ethnic groups (all p < 0.0001). miR-101 was overexpressed in breast cancers in the Indian patients. An in silico analysis of miR-423-5p showed that the AC genotype is mainly associated with Europeans (57%), while Asians display mostly CC (approx. 60%), and Africans mainly AA (approx. 60%). CONCLUSIONS: This study shows divergence in miR expression in breast cancers from different ethnic groups, and suggests that specific genetic variants in miR genes may affect breast cancer risk in these groups. Predicted targets of these miRs may uncover useful biomarkers that could have clinical value in breast cancers in different ethnic groups. PMID- 29791913 TI - Lymphadenectomy and Adjuvant Therapy Improve Survival with Uterine Carcinosarcoma: A Large Retrospective Cohort Study. AB - OBJECTIVE: Uterine carcinosarcoma is a rare, aggressive subtype of endometrial cancer. Treatment consists of hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy (LND). The survival benefit of LND in relation to adjuvant radio- and/or chemotherapy is unclear. We evaluated the impact of LND on survival in relation to adjuvant therapy in uterine carcinosarcoma. METHODS: Retrospective data on 1,140 cases were combined from the Netherlands Cancer Registry (NCR) and the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). LND was defined as the removal of any nodes. Additionally, cases where 10 nodes or less (LND <=10) or more than 10 nodes (LND > 10) were removed were analyzed separately. Adjuvant therapy was evaluated as radiotherapy, chemotherapy, or radiochemotherapy. Associations were analyzed by chi2 test, log rank test, and Cox regression analysis. RESULTS: Overall survival (OS) had improved after total abdominal hysterectomy with bilateral salpingo-oophorectomy with LND > 10 (HR 0.62, 95% CI 0.47-0.83). Adjuvant therapy was related to OS with an HR of 0.64 (95% CI 0.54-0.75) for radiotherapy, an HR of 0.65 (95% CI 0.48-0.88) for chemotherapy, and an HR of 0.25 (95% CI 0.13-0.46) for radiochemotherapy. Additionally, adjuvant treatment was related to OS when lymph nodes were positive (HR 0.22, 95% CI 0.11-0.42), but not when they were negative. CONCLUSION: LND is related to improved survival when more than 10 nodes are removed. Adjuvant therapy improves survival when LND is omitted, or when nodes are positive. PMID- 29791914 TI - Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease. AB - BACKGROUND/AIMS: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. METHODS: In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. RESULTS: We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. CONCLUSION: Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. PMID- 29791915 TI - Costaria costata Extract Suppresses Development of Atopic Dermatitis in chloro 2,4-dinitrobenzene-treated NC/Nga Mice. AB - We investigated the potential effects of Costaria costata (CC) on atopic dermatitis (AD) development in chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. CC is a brown alga distributed across the seas of Korea, China, and Japan. A total of 40 mice were randomly assigned to 5 groups with 8 mice per group: untreated Balb/c mice, AD control (0.1% w/v DNCB-treated NC/Nga mice), positive control (i.e., DNCB-treated NC/Nga mice fed a dietary supplement of 66.6 mg/kg of body weight [b.w.] of CJLP133), DNCB-treated NC/Nga mice fed a dietary supplement of 100 mg/kg b.w. of CCE10 (CCE10 100), and DNCB-treated mice fed a dietary supplement of 300 mg/kg b.w. of CCE10 (CCE10 300) groups. The CCE10 100 and CCE10 300 treatment groups suppressed AD development including clinical and histopathological changes and a reduction in skin hydration induced by DNCB. In addition, Th2 cytokine production in primary splenocytes, serum IgE and histamine production, and mast cell infiltration into the skin were suppressed in the CCE10 300 mice compared to the CCE10 100 mice. Our finding demonstrated an inhibitory effect of CCE10 in AD development by means of improving the Th1/Th2 cytokine balance and anti-inflammatory effect in an in vivo model. PMID- 29791916 TI - Diclofenac Sodium 3% in Hyaluronic Acid 2.5% Gel Significantly Diminishes the Actinic Keratosis Area and Severity Index. AB - BACKGROUND/AIMS: Actinic keratosis area and severity index (AKASI) is a new assessment tool to quantify the severity of actinic damage on the head. Thus far, it has not been evaluated in monitoring the efficacy of field-directed topical treatments in actinic keratosis (AK) in routine clinical practice. Thus, the aim of this study was to determine treatment outcomes by using AKASI 3 months after the initiation of topical application of diclofenac sodium 3% in hyaluronic acid 2.5% gel (DFS) in patients with AKs on the head. METHODS: We performed a retrospective analysis of patients with AKs who had AKASI scores prior to and after treatment with DFS. RESULTS: Of the 24 patients included, 20 (83.3%) showed an improvement in AKASI, 2 (8.3%) a stable AKASI, and 2 (8.3%) a worsening of AKASI after a median (interquartile range) follow-up period of 91.5 days (89.8 104.3). The median AKASI reduction was 31.4% (16.7-59.1). The Wilcoxon test showed significant differences (p = 0.0008) between baseline and posttreatment AKASI values. CONCLUSIONS: AKASI is an easy-to-use quantitative tool for assessing the treatment outcome of field-directed therapies. Field-directed therapies of AK should no longer be monitored by assessments based on lesion counts alone. PMID- 29791917 TI - Hybrid Diffuse Reflectance Spectroscopy: Non-Erythemal in vivo Testing of Sun Protection Factor. AB - BACKGROUND/AIMS: In order to define a label sun protection factor (SPF) of topically applied sunscreens, in vivo test methods like ISO 24444, FDA guideline, or the Australian standard are used worldwide. The basis of all these methods is provoking an erythemal skin reaction by UV irradiation to find the level of unprotected and protected minimal erythemal doses (MED). In vitro methods replacing the human skin by any kind of non-human material are still not available. Thus, offering the new hybrid diffuse reflectance spectroscopy (HDRS) technique that is able to stay on an in vivo level for SPF testing but meanwhile neglecting the UV-dose-related erythemal skin reaction is a perfect combination to take care of sun protection and any ethical concerns in SPF testing nowadays. METHODS: HDRS is a combination of in vivo diffuse reflectance spectroscopy (DRS) measurements on the skin and in vitro transmission measurements of a sunscreen on a roughened polymethylmethacrylate plate. By this technique, the in vivo behavior of the investigated sunscreen on the skin is measured as well as the UVB absorption, which is still non-visible in the reflectance technique. In order to establish an alternative method for in vivo SPF testing, a huge number of sunscreens (80 samples) was measured by HDRS and compared to the worldwide accepted standard ISO 24444. The variety of sunscreens measured reflects a wide range of different types of formulations as well as a wide range of SPFs (5-120) to validate this new alternative SPF testing procedure. RESULTS: The applied quantity of product as well as skin color dependencies of signal generation are shown to support any basic correlation of DRS signal generation and sun protection expectations. Far-reaching statistical data analyses show an excellent link of the new non-erythemally driven HDRS-SPF technique and ISO 24444 results. In the same way, HDRS-UVA-PF results can be correlated with UVA-PF values calculated from ISO 24443. CONCLUSION: Due to the elimination of any erythemal relevant UVB and UVA doses, absolutely no skin reaction occurs. Consequently there is no need to define a MED any more. For the first time an alternative way to SPF is shown without any ethical concerns of SPF testing in vivo and/or any restriction of SPF testing in vitro. Regardless of the type of formulation or the level of protection, an excellent correlation of SPFHDRS and SPF24444 for sunscreen labeling could be found. By this new alternative non-erythemal technique, not only SPF values can be measured, but also UVA-PF values can be calculated with an excellent correlation to ISO 24443 from the same set of data. For the first time a robust alternative test method of SPF- and UVA-PF values is described, taking into account the interaction of sunscreen formulation and skin. PMID- 29791921 TI - Does GastroPlus Support Similarity and Dissimilarity Factors of in vitro-in vivo Prediction in Biowaiver Studies? A Lower Strength Amlodipine As a Model Drug. AB - BACKGROUND: Many generic pharmaceutical products are currently available on the market place worldwide. Recently, there is a growing concern on the quality and efficacy of generic products. However, health care professionals such as physicians and pharmacists are in difficult situations to choose among alternatives. PURPOSE: The aim of this study is to assess the effectiveness of the in silico technique (Gastro Plus(r)) in the biowaiver study and whether similarity and dissimilarity factors (f 2 and f 1 respectively) are effective in this regard. METHOD: The concentration of amlodipine in the sample was calculated by comparing the absorbance of the sample with that of a previously prepared amlodipine standard solution using validated HPLC method. The dissolution profile for each product (brand and generics) was constructed. The similarity (f2) and dissimilarity (f 1) factors were calculated for the generic product according to equation 1 and 2. GastroPlusTM software (version 9.0, Simulations Plus Inc., Lancaster, CA, USA) was used to predict the absorption profiles of amlodipine from the generic product Amlovasc(r) and the reference Norvasc(r). CONCLUSION: These results may provide a rationale for the interchangeability between the RLD and generic version based on in vitro release profiles in silico technique especially in a lower strength dose drug. PMID- 29791922 TI - P2Y12 Polymorphisms and the Risk of Adverse Clinical Events in Patients Treated with Clopidogrel: A Meta-Analysis. AB - BACKGROUND AND STUDY AIM: Some studies have reported an association between P2Y12 gene polymorphisms and clopidogrel adverse outcomes with inconsistent results. We aimed to explore the relationship between P2Y12 polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel through a meta analysis. METHODS: A systematic search of PubMed, Web of Science and the Cochrane Library was conducted. Retrieved articles were comprehensively reviewed and eligible studies were included, and the relevant data was extracted for this meta analysis. All statistical tests were performed by the Review Manager 5.3 software. RESULTS: A total of 14 studies involving 8,698 patients were included. In the Han Chinese population, ischemic events were associated with P2Y12 T744C polymorphism in the CC vs TT+CT genetic model (OR=3.32, 95%CI=1.62-6.82, P=0.001), and the events were associated with P2Y12 C34T polymorphism in the TT+TC vs CC genetic model (OR=1.70, 95%CI=1.22-2.36, P=0.002). However, ischemic events were not related to P2Y12 G52T polymorphism (TT+TG vs GG: OR=1.13, 95%CI=0.76-1.68, P=0.56; TT vs GG+TG: OR=2.02, 95%CI=0.65-6.28, P=0.22). The associations between the P2Y12 polymorphism and ischemic events were not significant in T744C, G52T and C34T genotype for another subgroup of the Caucasian population (P>0.05). Only two studies referring to bleeding events were included in this analysis of C34T polymorphism, and no significant association was found (TT+TC vs CC: OR=1.07, 95%CI=0.37-3.15, P=0.90). CONCLUSIONS: In the Caucasian population, P2Y12 gene polymorphisms are not associated with clinical events. However, in the Chinese Han population, P2Y12 T744C and C34T polymorphisms are significantly associated with adverse clinical events. PMID- 29791923 TI - Inhaled Treprostinil-Prodrug Lipid Nanoparticle Formulations Provide Long-Acting Pulmonary Vasodilation. AB - Treprostinil (TRE), a prostanoid analogue approved in the USA for the treatment of pulmonary arterial hypertension, requires continuous infusion or multiple dosing sessions per day for inhaled and oral routes of administration due to its short half-life. The inhaled drug is known to induce adverse systemic and local effects including headache, nausea, cough, and throat irritation which may be due at least in part to transiently high drug concentrations in the lungs and plasma immediately following administration [1]. To ameliorate these side effects and reduce dosing frequency we designed an inhaled slow-release TRE formulation. TRE was chemically modified to be an alkyl prodrug (TPD) which was then packaged into a lipid nanoparticle (LNP) carrier. Preclinical screening in a rat model of hypoxia-induced pulmonary vasoconstriction led to selection of a 16-carbon alkyl ester derivative of TRE. The TPD-LNP demonstrated approximately 10-fold lower TRE plasma Cmax compared to inhaled TRE solution while maintaining an extended vasodilatory effect. The favorable PK profile is attributed to gradual dissociation of TPD from the LNP and subsequent conversion to TRE. Together, this sustained presentation of TRE to the lungs and plasma is consistent with a once- or twice-daily dosing schedule in the absence of high Cmax-associated adverse events which could provide patients with an improved treprostinil therapy. PMID- 29791924 TI - Return to Sport after ACL Surgery: A Comparison between Two Different Reconstructive Techniques. AB - The anterior cruciate ligament reconstruction (ACLR) has become a very common surgical procedure. One of the main success indicators of the surgical procedure is the return to preinjury sporting level. In recent years, reconstructive techniques have been geared toward less morbidity and optimized ligaments process to speed up the recovery of sports activity. This study compares clinical and imaging data, to evaluate the timing of return to sport, of two populations undergoing ACLR using two different techniques: ACLR with hamstring maintaining tibial insertion (MHG) and an all-inside technique with complete hamstring detachment (DHG). Patients were clinically evaluated with Marx rating scale, International Knee Documentation Committee (IKDC) score, and Tegner activity scale at a minimum follow-up (FU) of 4 years. The two groups have homogeneous characteristics: age, sex, type, and level of sports activity. Since November 2012, 59 patients with unilateral ACL insufficiency underwent ACLR: 31 patients using the MHG technique and 28 patients using the DHG technique. In both groups, a significant improvement in the clinical scores of the administered tests was observed. The MHG group reported a higher percentage of normal knees (83.8%) compared with the DHG group (78.6%). IKDC subjective score improved at each FU. Comparing the two techniques, at 12 months' FU the MHG group achieved better IKDC results (89.6) compared with the DHG technique (84.2). Marx and Tegner score values improved over time reaching comparable results at final FU. At final FU, 98% of patients returned to the same preinjury professional sporting level. Both techniques have been able to provide good clinical results. The MHG group, however, had a resumption of sports activity of the same level and intensity slightly longer (6.3 months) than that in the DHG group (5.9 months). Furthermore, the resumption of training and athletic gestures for the type of sport practiced was earlier than the DHG group. However, in the long run the level of sporting activity leveled in both groups, demonstrating the effectiveness of both techniques. PMID- 29791925 TI - Patient-Specific Instrumentation Affects Perioperative Blood Loss in Total Knee Arthroplasty. AB - Patient-specific instrumentation (PSI) may contribute to reduced blood loss related to total knee arthroplasty (TKA). The purpose of this study was to compare the estimated hemoglobin (Hb) and red blood cell volume (RBC) losses in two groups of patients undergoing TKA with PSI and conventional instrumentation. Pre- and postoperative blood samples were collected from 22 patients randomly assigned to receive a PSI-assisted or conventional TKA. Post- to preoperative Hb difference was calculated and RBC loss was estimated according to Sehat et al. A significant difference in Hb reduction in favor of the PSI group was registered on the last day of stay (p = 0.0084) and significant treatment effect (p = 0.027) on Hb reduction after intervention was found with a regression model for longitudinal measurements. This study demonstrated that PSI leads to a significant trend in earlier Hb regain. These promising results suggest a beneficial effect of PSI in blood loss reduction. PMID- 29791926 TI - Meniscus Repair in Children and Adolescents: A Systematic Review of Treatment Approaches, Meniscal Healing, and Outcomes. AB - Although the consequences of traumatic meniscus tears and the importance of meniscal repair are well-established in adults, the same cannot be said for the young population. Better evidence regarding the outcomes following traumatic meniscal tears in children would improve our understanding of this increasing pathology and help define important factors in deciding the best treatment option. A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines using the Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, and MEDLINE PubMed databases. Inclusion criteria were as follows: studies reporting the outcomes of meniscal repair in patients 18 years old or younger, with a minimum mean follow-up of 12 months, Portuguese, Spanish, or English languages, and human studies including 10 or more patients. Our search identified 2,534 individual titles. After application of the inclusion and exclusion criteria, 8 studies were included, evaluating 287 patients with repaired meniscal tears. All eight studies were classified as level of evidence IV. The mean methodological index for nonrandomized studies score was 8.6 +/- 1.4. Meniscal repair included all meniscal zones and tear patterns. Anterior cruciate ligament tear was the most common associated injury. The all-inside and inside-out techniques were predominantly reported. The majority of the patients reported good to excellent outcomes and had clinical signals of meniscal healing; meniscectomies following meniscal repair were performed in just 44 cases. In conclusion, meniscal tears in pediatrics are not uncommon. Repairs of this injury were associated with good to excellent outcomes in most patients, regardless of the injury pattern, zone, or technique. Reported complications were minimal; however, higher quality studies are needed to confirm the findings of this systematic review. This is a systematic review study with Level IV. PMID- 29791927 TI - Treatment Outcome of Reconstruction for Isolated Posterior Cruciate Injury: Subjective and Objective Evaluations. AB - There is no consensus regarding the treatment method and outcome of posterior cruciate ligament (PCL) injury. We hypothesized that although the outcome of PCL reconstruction was favorable in terms of knee stability, the outcome was unsatisfactory in terms of patient-based assessments. The purpose of this study is to evaluate the treatment outcomes of knees that underwent reconstruction for PCL injury by subjective and objective assessments, and to analyze the correlation between various assessments. Twenty-three patients who underwent PCL reconstruction were studied. All reconstructions were performed arthroscopically by the single-bundle technique using a hamstring tendon autograft. Patients were evaluated clinically before operation and 24 months after operation using the 36 Item Short Form Health Survey (SF-36) which is a patient-based health assessment survey, Lysholm score, tibial translation ratio, Visual Analogue Scale (VAS) for pain, and range of motion (ROM) in the knee. The correlation of these assessment methods was analyzed. For the SF-36 survey, significant improvement was observed after operation in only 3 of 7 subscales compared with before surgery. Furthermore, the scores reached the national standard scores in only 3 subscales. While the Lysholm score and tibial translation ratio were improved significantly, no significant improvement in the VAS pain score was observed. For ROM assessment, approximately 30% of the patients had flexion restriction after operation, and the degree of restriction correlated positively with the VAS score. The present results indicated that although the outcome of PCL reconstruction was favorable in terms of knee stability and motor function, the outcome was unsatisfactory in terms of patient-based assessments. Since pain associated with flexion restriction appears to be a poor prognostic factor and there is a dissociation between subjective and objective assessments, improvement of the surgical method is necessary. PMID- 29791928 TI - The Impact of Medical Comorbidities on Primary Total Knee Arthroplasty Reimbursements. AB - Medical comorbidities have been shown to cause an increase in peri-and postoperative complications following total knee arthroplasty (TKA). However, the increase in cost associated with these complications has yet to be determined. Factors that influence cost have been of great interest particularly after the initiation of bundled payment initiatives. In this study, we present and quantify the influence of common medical comorbidities on the cost of care in patients undergoing primary TKA. A retrospective level of evidence III study was performed using the PearlDiver supercomputer to identify patients who underwent primary TKA between 2007 and 2015. Patients were stratified by medical comorbidities and compared using analysis of variance for reimbursements for the day of surgery and over 90 days postoperatively. A cohort of 137,073 US patients was identified as having undergone primary TKA between 2007 and 2015. The mean entire episode-of care reimbursement was $23,701 (range: $21,294-26,299; standard deviation [SD] $2,611). The highest reimbursements were seen in patients with chronic obstructive pulmonary disease (mean $26,299; SD $3,030), hepatitis C (mean $25,662; SD $2,766), morbid obesity (mean $25,450; SD $2,154), chronic kidney disease (mean $25,131, $3,361), and cirrhosis (mean $24,890; SD $2,547). Medical comorbidities significantly impact reimbursements, and therefore cost, after primary TKA. Comprehensive preoperative optimization for patients with medical comorbidities undergoing TKA is highly recommended and may reduce perioperative complications, improve patient outcome, and ultimately reduce cost. PMID- 29791929 TI - Documenting Routinely What Matters to People: Standardized Headings for Health Records of Patients with Chronic Health Conditions. AB - OBJECTIVE: Specifying the content in electronic health records (EHRs) through standardized headings based on international reference classifications will facilitate their semantic interoperability. The objective of this study was to specify potential chapter headings for EHRs aligned with the World Health Organization's (WHO) International Classification of Functioning, Disability, and Health (ICF) based on the perspectives of people living with chronic health conditions, carers, and professionals. METHODS: A multistage process was established including (1) a patient workshop, (2) an online survey of both patients and carers, and (3) an online consultation with patient and professional bodies. The ICF served as a starting point. Based on the first stage, a first draft of the headings was developed and further refined based on the feedback at each stage. We examined in a fourth step whether items from existing assessment tools support the operationalization of the identified headings. Therefore, we used the WHO Disability Assessment Schedule 2.0 (WHODAS2.0), a patient-reported instrument, and interRAI, a clinician-administered instrument. RESULTS: The first workshop was attended by eight people, the survey was completed by 250 persons, and the online consultation received detailed feedback by 18 professional bodies. This study resulted in 16 potential chapter headings for EHRs which capture aspects related to the body, such as emotions, motivation, sleep, and memory or thoughts, to being involved in social life, such as mobility, social activities, and finances, as well as to the care process, such as understanding of health issues and treatment or care priorities and goals. When using the WHODAS2.0 and interRAI together, they capture all except one of the proposed headings. CONCLUSION: The identified headings provide a high level structure for the standardized recording, use, and sharing of information. Once implemented, these headings have the potential to facilitate the delivery of personalized care planning for patients with long-term health problems. PMID- 29791931 TI - Effectiveness of a Crocus sativus Extract on Burn Wounds in Rats. AB - Crocus sativus is a spice with various pharmacological properties. Crocin, picrocrocin, and safranal are the main compositions of saffron that have recently been considered in the therapy of many diseases. High-performance liquid chromatography analysis revealed presence of these compounds in our saffron extract. This study was carried out to evaluate the effect of saffron on burn wound healing at an in vivo model. Saffron was topically applied on burn wounds in rats; the percentage of wound closure, wound contraction, and the levels of main cytokines and growth factors were measured. The saffron extract was also applied to evaluate the proliferation and migration of human dermal fibroblast (HDF) cells using in vitro scratch assay and resulted in active proliferation and migration of the HDF cells in a dose-dependent manner. A clear enhanced healing was observed in the saffron-treated wounds compared to the silver sulfadiazine and negative control groups. Decreased expression of interleukin-1beta and transforming growth factor-beta1 (TGF-beta1) during the inflammatory phase demonstrated the role of saffron in promoting wound healing. In addition, enhanced TGF-beta1 expression during the proliferative phase and basic fibroblast growth factor during the remodeling phase represented regenerative and anti scarring role of saffron, respectively. Our histological and biochemical findings also confirmed that saffron significantly stimulated burn wound healing by modulating healing phases. Therefore, saffron can be an optimal option in promoting skin repair and regeneration. Application of this herbal medicinal drug should be encouraged because of its availability and negligible side effects. PMID- 29791930 TI - The Pediatric Emergency Care Applied Research Network Registry: A Multicenter Electronic Health Record Registry of Pediatric Emergency Care. AB - BACKGROUND: Electronic health record (EHR)-based registries allow for robust data to be derived directly from the patient clinical record and can provide important information about processes of care delivery and patient health outcomes. METHODS: A data dictionary, and subsequent data model, were developed describing EHR data sources to include all processes of care within the emergency department (ED). ED visit data were deidentified and XML files were created and submitted to a central data coordinating center for inclusion in the registry. Automated data quality control occurred prior to submission through an application created for this project. Data quality reports were created for manual data quality review. RESULTS: The Pediatric Emergency Care Applied Research Network (PECARN) Registry, representing four hospital systems and seven EDs, demonstrates that ED data from disparate health systems and EHR vendors can be harmonized for use in a single registry with a common data model. The current PECARN Registry represents data from 2,019,461 pediatric ED visits, 894,503 distinct patients, more than 12.5 million narrative reports, and 12,469,754 laboratory tests and continues to accrue data monthly. CONCLUSION: The Registry is a robust harmonized clinical registry that includes data from diverse patients, sites, and EHR vendors derived via data extraction, deidentification, and secure submission to a central data coordinating center. The data provided may be used for benchmarking, clinical quality improvement, and comparative effectiveness research. PMID- 29791932 TI - B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss. AB - Mutations in B3GALNT2, encoding a glycosyltransferase enzyme involved in alpha dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2-related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2. The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker-Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2 related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2-related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype-phenotype correlation in these cases. PMID- 29791933 TI - Infantile Basal Ganglia Stroke after Mild Head Trauma Associated with Mineralizing Angiopathy of Lenticulostriate Arteries: An Under Recognized Entity. AB - Basal ganglia infarction in young children, mostly after mild head trauma, has been repeatedly reported. The pathogenesis and the risk factors are not fully understood. Lenticulostriate vasculopathy, usually referred to as basal ganglia calcification, is discussed as one of them. We describe five young (7-13 months old on presentation) male children who suffered from hemiparesis due to ischemic stroke of the basal ganglia, four of them after minor head trauma. All of them had calcification in the basal ganglia visible on computed tomography or cranial ultrasound but not on magnetic resonance imaging. Follow-up care was remarkable for recurrent infarction in three patients. One patient had a second symptomatic stroke on the contralateral side, and two patients showed new asymptomatic infarctions in the contralateral basal ganglia on imaging. In view of the scant literature, this clinic-radiologic entity seems under recognized. We review the published cases and hypothesize that male sex and iron deficiency anemia are risk factors for basal ganglia stroke after minor trauma in the context of basal ganglia calcification in infants. We suggest to perform appropriate targeted neuroimaging in case of infantile basal ganglia stroke, and to consider prophylactic medical treatment, although its value in this context is not proven. PMID- 29791934 TI - Discrepancies Between Nomenclature and Indications of Psychotropics. AB - INTRODUCTION: While the current nomenclature of psychotropic drugs is disease based, their approved indications do not always match their classifications. METHODS: Information on approved indications of "second-generation antipsychotics" and "newer antidepressants" that are available in the United States (US), the United Kingdom (UK), France, Germany, and Japan were extracted from their packet inserts. RESULTS: A significant proportion of "atypical antipsychotics" were approved for psychiatric conditions other than psychotic disorders (i. e., bipolar disorder, major depressive disorder, and autistic disorder) as follows: 76.9% in the US, 66.7% in the UK, 66.7% in France, 60.0% in Germany, and 44.4% in Japan. Likewise, more than half of "newer antidepressants" had approved indications for psychiatric conditions other than depression (e. g., panic disorder, obsessive compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder): 56.3% in the US, 69.2% in the UK, 69.2% in France, 50.0% in Germany, and 62.5% in Japan. CONCLUSIONS: Our results raise concerns regarding generic terminologies of "antipsychotics" and "antidepressants" since the conventional indication-based nomenclature does not fit well with the official indication. PMID- 29791935 TI - [Impact of OSA Therapy on Established Polyphasic Sleep]. AB - AIM OF STUDY: The prevalence of polyphasic sleep (PS) in patients with sleep apnoea (OSA) is investigated in this study. In established PS the possible impact of OSA therapy on sleep behaviour was examined. METHODS: Sleep patterns in 24 hours of initial recepted OSA patients were recorded by questionnaire (n = 163). In polyphasic sleepers the sleep patterns were reevaluated after OSA therapy initiation. In additional patients polyphasic therapy usage was investigated by telemonitoring data (n = 487). RESULTS: 39,6 % of the patients had PS. After OSA therapy initiation in 97,0 % of the polyphasic sleepers a monophasic device usage was established while 3,0 % had a polyphasic usage. PS was switched to monophasic sleep in 81,8 % of the patients. 15.2 % had preserved PS without device usage on daytimes. 2,9 % of the telemonitoring patients showed a polyphasic usage pattern. CONCLUSIONS: The prevalence of PS in OSA patients is higher than in the general population. PS is converted to monophasic sleep in 81,8 % after OSA therapy initiation. In preserved PS the majority of patients doesn't use the therapy while napping. Polyphasic device usage was 2,9 % in telemonitoring patients and 3,0 % of the controls of this study. PMID- 29791936 TI - Is Right Sleeve Lower Lobectomy Necessary? Is It Safe? AB - OBJECTIVES: The right sleeve lower lobectomy is the least used of the bronchial sleeve operations. There are only case-based studies in the literature. In this study, we compared this technique to those used in patients who underwent a right lower bilobectomy. METHODS: We retrospectively reviewed the data of patients who had been operated on due to non-small cell lung cancer (NSCLC) from January 2005 to December 2015 from a dataset that was formed prospectively. Of the 4,166 patients who underwent resections due to NSCLC, the files of those who had a right sleeve lower lobectomy (group S) and those who had a right lower bilobectomy (group B) were evaluated. The remaining 25 patients in group B and 18 patients in group S were compared in terms of demographic data, morbidity, hospitalization time, mortality, histopathology, recurrence, and total survival. RESULTS: No significant differences in the demographic or clinical characteristics were observed between the two groups, except that group S had more female patients. Postoperative complications developed in 52% of the patients in group B and 11.1% of the patients in group S (p = 0.006). Mean hospitalization time was 9.6 +/- 3.6 (range, 6-19) days in group B and 6.72 +/- 1.5 (range, 4-9) days in group S (p = 0.001). All patients received complete resections. The mean patient follow-up time was 42.9 months. No significant difference was found between local and distant recurrences (p = 1, p = 0.432). Mean survival time was 89.6 months (5-year rate = 73%), which was 90.6 months (5 year rate = 75.3%) in group B and 63.1 months (5-year rate = 69.3%) in group S (p = 0.82). CONCLUSION: This technique allows for reduced filling of the thoracic cavity by a prolonged air leak and a reduced prevalence of complications. Additionally, the hospitalization time is shortened. It does not produce any additional mortality burden, and total survival and oncological outcomes are reliable. This technique can be used in selected patients at experienced centers. PMID- 29791937 TI - Nicoline Schiess, MD, MPH. PMID- 29791938 TI - The Importance of Global Medical Collaboration. PMID- 29791939 TI - Neurology Training Worldwide. AB - Neurology training is essential for providing neurologic care globally. Large disparities in availability of neurology training exist between higher- and lower income countries. This review explores the worldwide distribution of neurology training programs and trainees, the characteristics of training programs in different parts of the world, and initiatives aimed at increasing access to neurology training in under-resourced regions. PMID- 29791940 TI - Global Neurology: Navigating Career Possibilities. AB - Neurology has not typically been associated with international relief work; however, with the growth of chronic cardiovascular disease and stroke associated with unhealthy eating and sedentary ways, the appearance of "new" neurologic diseases, such as the Zika and West Nile viruses, and the high numbers of seizure disorders resulting from neuroinfectious diseases, more opportunities are arising for international and globally oriented neurologists. Multiple opportunities exist for developing a global clinician-educator career pathway, including private institutions, nongovernmental organizations, government-funded opportunities such as Medical Education Partnership Initiative, Fogarty and Fulbright Scholarships, and the American Academy of Neurology's Global Health Section. Furthermore, increasing research capacity in developing countries and increased funding opportunities for global health research have led to new opportunities for neurologists to establish global health research careers. These opportunities could not have come at a better time, as many faculty members have noted a particularly strong interest in global neurology from medical students and residents. Career categories and opportunities for neurologists desiring to work globally are discussed along with the emerging "global neurologist" academic pathway. PMID- 29791941 TI - Understanding Refugees' Health. AB - According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health profile is markedly different from that of the population in the country of asylum. The aim of this study is to review the major issues physicians need to be aware of when treating asylum seekers, with a special focus on the neurological problems of asylum seekers and refugees. The major impact factors on refugees' health are linked to experiences and exposure (1) in the country of origin, (2) in refugee camps and en route to Europe, and (3) in the process of immigration into the host country and living in European asylum centers. Refugees' health is also affected by psychological problems and by infectious diseases. Additionally, chronic diseases resulting in polymorbidity, cancer, and neurological diseases are easy to overlook and demand special attention. Neurological injuries/diseases may be traumatic (e.g., spinal cord injuries), posttraumatic (e.g., chronic pain syndromes), the result of cerebral infections, or the consequences of starvation (e.g., epilepsy, ataxia, and paraesthesia). The main challenges for physicians are lack of awareness of the asylum seekers' specific health care problems, language and intercultural communication problems, as well as access and integration of asylum seekers into the health care system. The health issues of asylum seekers are manifold and challenging to physicians. Awareness of these conditions is mandatory to ensure good clinical practice for this patient population, which has a huge burden in chronic, infectious, mental, and neurological diseases. PMID- 29791942 TI - Emerging Viral Infections and Their Impact on the Global Burden of Neurological Disease. AB - Emerging viral infections of the nervous system represent a major global public health concern in the 21st century. They are caused primarily by RNA viruses and are mostly associated with acute or subacute encephalitis. The spectrum of associated central or peripheral nervous system disorders is broad, and results either from a direct viral effect or due to the host immune responses against the infection. Emerging viral infections impose substantial neurological morbidity and mortality, particularly in low- and middle-income regions. In the past five decades, vector-borne viruses primarily transmitted by arthropods, or arboviruses, have been responsible for epidemics with a high burden of neurological disease, like the 2015-2016 Zika virus epidemic in the Americas. Viruses that have become neurovirulent for humans after geographical expansion include West Nile, Dengue, and Zika viruses. Factors such as animal migration, disruption of ecological niches, and cross-species contact have caused old viruses to reappear and cause neurological disease, as is the case of Ebola virus. In addition to these biological challenges, current preventive strategies, vaccination, and diagnostic and therapeutic approaches remain limited. We review the clinical-virological features and global impact of the most relevant emerging viral infections of the nervous system as they are projected over the 21st century. PMID- 29791943 TI - The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism". AB - "Stem cell tourism" is defined as the unethical practice of offering unproven cellular preparations to patients suffering from various medical conditions. This phenomenon is rising in the field of neurology as patients are requesting information and opportunities for treatment with stem cells for incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, despite their clinical research and experimental designation. Here, we review the recent trends in "stem cell tourism" in both the United States and abroad, and discuss the recent reports of neurological complications from these activities. Finally, we frame critical questions for the field of neurology regarding training in the ethical, legal, and societal issues of the global "stem cell tourism," as well as suggest strategies to alleviate this problem. Although there are ongoing legitimate clinical trials with stem cells for neurological diseases, procedures offered by "stem cell clinics" cannot be defined as clinical research. They lack the experimental and state-of-the-art framework defined by peers and the FDA that focus on human research that safeguard the protection of human subjects against economical exploitation, unwanted side effects, and futility of unproven procedures. "Stem cell tourism" ultimately exploits therapeutic hope of patients and families with incurable neurological diseases and can put in danger the legitimacy of stem cell research as a whole. We posit that an improvement in education, regulation, legislation, and involvement of authorities in global health in neurology and neurosurgery is required. PMID- 29791944 TI - The Global Burden of Headache. AB - At the turn of the century, most of the world's population lived in regions where the prevalence of headache was unknown and its impact poorly understood. Lifting The Burden (LTB), a nonprofit organization in official relations with the World Health Organization, established the Global Campaign against Headache, with the ultimate purpose of reducing the burden of headache worldwide. First, the scope and scale of this burden had to be known. LTB embarked upon a program of population-based studies in countries in all world regions in order to achieve its aim. Its studies have demonstrated a high prevalence of headache disorders, including migraine, tension-type headache, and medication-overuse headache, and their associations with impaired quality of life, substantial lost productivity, and high economic costs in every country surveyed. Informed by these, the Global Burden of Disease study ranks headache disorders as the second leading cause of years lived with disability worldwide; migraine alone is third among people aged 15 to 49 years. With interventions urgently needed to reduce these burdens throughout the world, we review the epidemiological studies conducted by LTB, examine proposed interventions to improve provision of headache care including a three-tier system of structured headache services, and consider the challenges still remaining in providing effective, efficient, and equitable headache care especially in low-income countries. PMID- 29791945 TI - Global Health: Epilepsy. AB - Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone-related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own. PMID- 29791947 TI - Global Burden of Stroke. AB - Stroke is the second leading cause of death and a major cause of disability worldwide. Its incidence is increasing because the population ages. In addition, more young people are affected by stroke in low- and middle-income countries. Ischemic stroke is more frequent but hemorrhagic stroke is responsible for more deaths and disability-adjusted life-years lost. Incidence and mortality of stroke differ between countries, geographical regions, and ethnic groups. In high-income countries mainly, improvements in prevention, acute treatment, and neurorehabilitation have led to a substantial decrease in the burden of stroke over the past 30 years. This article reviews the epidemiological and clinical data concerning stroke incidence and burden around the globe. PMID- 29791946 TI - Global Health: Pediatric Neurology. AB - Neurologic disorders contribute significantly to both morbidity and mortality among children in resource-limited settings, but there are a few succinct studies summarizing the epidemiology of neurologic disorders in these settings. A review of available literature was performed to identify data on the prevalence, etiology, outcomes, and treatment of neurologic disorders in children in resource limited settings. The burden of neurologic disorders in children is high in resource-limited settings. Barriers to optimal care include lack of trained personnel, limited access to diagnostic technology, and limited availability of drugs used to treat common conditions. Several solutions have been suggested to deal with these challenges including increased collaborations to train neurologists willing to practice in resource-limited settings and increased training of physician extenders or community health workers. Further studies are necessary to improve our understanding of the epidemiology of neurologic disorders in resource-limited settings. Future epidemiologic studies should incorporate multiple countries in resource-limited settings and utilize standardized definitions and methodologies to enable comparison across regions. PMID- 29791948 TI - Multiple Sclerosis. AB - Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a significant contribution from B cells and cells of the innate immune system. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease. The diagnosis of MS remains clinical despite recent advances in diagnostics and relies on demonstrating dissemination in space and time while excluding alternative diagnoses. The Mc Donald diagnostic criteria, with their recent 2017 revision, are currently widely accepted in the MS community. Although no cure is yet available, many disease-modifying therapies (DMTs) have shown different levels of efficacy in preventing relapses, accumulation of lesions on magnetic resonance imaging (MRI), and disability progression. Current treatment strategies include gradual escalation based on clinical and radiological criteria that determine treatment response, or initial induction with high efficacy DMTs especially in patients with an early aggressive course. PMID- 29791950 TI - Global Health Neurology: HIV/AIDS. AB - With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the world, many of whom reside in resource-limited settings. The majority of studies have focused on individuals residing in the developed world, while the impact of HIV disproportionately affects people living in developing countries. This review focuses on recent domestic and international studies regarding neurologic complications related to HIV, including opportunistic infections, peripheral neuropathy, cerebrovascular disease, and HIV-associated neurocognitive disorders, in light of the growing population affected by these conditions. PMID- 29791949 TI - The Global Neurological Burden of Tuberculosis. AB - Central nervous system (CNS) involvement of tuberculosis (TB) is the most severe manifestation of TB and accounts for approximately 5 to 10% of all extrapulmonary TB (EPTB) cases and approximately 1% of all TB cases. TB meningitis (TBM) is the most common form of CNS TB, though other forms occur, often in conjunction with TBM, including intracranial tuberculomas, tuberculous brain abscesses, and spinal tubercular arachnoiditis. CNS TB often presents with nonspecific clinical features that mimic symptoms of other neurological conditions, often making diagnosis difficult. Defining neuroimaging characteristics of TBM include thick basal meningeal enhancement, hydrocephalus, and parenchymal infarctions most commonly involving the basal ganglia and internal capsule. Traditional cerebrospinal fluid sample analysis frequently requires lengthy times-to-result and have low sensitivity. Given the pitfalls of conventional CNS TB diagnostic methods, various molecular-based methods, including immunoassays and polymerase chain reaction (PCR)-based assays have emerged as alternative diagnostic tools due to their rapidity, sensitivity, and specificity. Expert panels on TBM have recently emphasized the need for standard research procedures with updated case definitions and standardized study methods, which will hopefully pave the way for more robust multicenter international studies. In this article, we review the epidemiology, diagnosis, molecular factors associated with disease presentation and outcome, and treatment of CNS TB. PMID- 29791951 TI - Nervous System Infections and the Global Traveler. AB - Neurological complications of infectious diseases are associated with high rates of morbidity and mortality. It is imperative that neurologists be up-to-date on current developments including typical and atypical presentations of neurological infections in travelers, diagnostic and treatment recommendations, and emerging pathogen resistance patterns to avoid fatal outcomes and long-term sequelae. This article will address concepts of emerging and reemerging infectious diseases, and will provide updates on the neurological manifestations of select emerging and reemerging infections, including Ebola virus, bacterial meningitis, enterovirus 71, Zika virus, cerebral malaria, and Japanese encephalitis. Emerging and reemerging neurotropic infectious diseases, including Zika virus, have recently been major global health threats. Factors contributing to the emergence of infectious diseases include closer contact with zoonoses, population growth in cities, globalization, environmental changes, and the rise in antibiotic resistance. Serotype replacement of bacterial meningitis, the possibility of viral persistence in the central nervous system in Ebola virus, antibiotic resistance of malaria, and the evolution of neurovirulent strains of Zika virus display some of the developing challenges that accompany various neurotropic infectious diseases. Neurologists should be aware of the factors contributing to the emergence and reemergence of neurotropic infectious diseases. As emerging and reemerging neurotropic infectious continue to be a major global health security threat, clinicians should be aware of the risks to travelers and current guidelines on prevention and management. PMID- 29791952 TI - Skin Punctures in Preterm Infants in the First 2 Weeks of Life. AB - OBJECTIVE: The objective of this study was to investigate frequency and trends of skin punctures in preterm infants. STUDY DESIGN: A prospective audit of preterm infants less than 35 weeks admitted over a 6-month period to a tertiary neonatal intensive care unit. Each skin puncture performed in the first 2 weeks of life was documented in a specifically designed audit sheet. RESULTS: Ninety nine preterm infants were enrolled. Infants born at < 32 weeks' gestation had significantly more skin punctures than infants > 32 weeks (median skin punctures 26.5 vs. 17, p-value < 0.05). The highest frequency of skin punctures occurred during the first week of life for infants > 28 weeks' gestation (medians 17.5 in 28-31 + 6 weeks' gestation, and 15 in > 32 weeks), and during the second week of life for those born at < 28 weeks (median 17.5). Infants with sepsis had more skin punctures (p-value < 0.001), but this was not significant on multivariate analysis. Median skin punctures in the second week of life were statistically higher in the sepsis group on multivariate analysis (odds ratio: 1.07, 95% confidence interval: 1.00-1.14, p = 0.041). CONCLUSION: Frequency of skin punctures is influenced by gestational age and postnatal age. Skin punctures were not an independent risk factor for sepsis. PMID- 29791953 TI - Past and Present: A Review of Antenatal Corticosteroids and Recommendations for Late Preterm Birth Steroids. AB - Since 1972, the beneficial neonatal effects of antenatal corticosteroids (ACSs) have been repeatedly demonstrated in pregnancies at risk of preterm birth before 34 weeks' gestation. While ACS utilization before 34 weeks has been high since the 1990s, knowledge gaps regarding the risks and benefits of ACS continue to exist. Recent evidence has been published regarding the benefit of ACS in the late preterm period. This review addresses the evidence and knowledge gaps for ACS use before and after 34 weeks' gestation. We also provide recommendations for ACS use in the late preterm period. PMID- 29791954 TI - Muscle and Nerve Imaging. PMID- 29791955 TI - Muscle-Tendon-Enthesis Unit. AB - Injuries to the muscle-tendon-enthesis unit are common and a significant source of pain and loss of function. This article focuses on the important anatomical and biomechanical considerations for each component of the muscle-tendon-enthesis unit. We review normal and pathologic conditions affecting this unit, illustrating the imaging appearance of common disorders on magnetic resonance imaging and ultrasound. Knowledge of the anatomy and biomechanics of these structures is crucial for the radiologist to make accurate diagnoses and provide clinically relevant assessments. PMID- 29791956 TI - Accessory Muscles of the Extremities. AB - Accessory muscles and variations are not uncommon at the upper and lower extremity. They are often overlooked because they are asymptomatic and present as incidental findings on imaging. However, they may present as a soft tissue swelling, thereby mimicking soft tissue tumors. Other symptoms are attributed to impingement on neurovascular structures and to exercise-related pain. Thorough knowledge of the anatomy, systematic imaging analysis, and the awareness of it are the clues to correct identification. On ultrasound, accessory muscles have a similar echotexture as other muscles, whereas the signal intensity on magnetic resonance imaging (MRI) is similar to muscle. Because of the intrinsic contrast with the adjacent intermuscular fat, accessory muscles are best depicted on MRI without fat suppression. This article provides a short overview of the anatomy of most prevalent accessory muscles of the upper and lower limb and its potential pathogenic nature. PMID- 29791957 TI - Myositis and Fasciitis: Role of Imaging. AB - Imaging plays an important role in the evaluation of patients presenting with possible myositis, with magnetic resonance imaging the most appropriate modality but ultrasound also playing a complementary role. This article reviews the imaging appearance of the inflammatory myopathies, other forms of myositis, and mimickers of myositis, with a discussion of distinguishing features for each entity. The fascia and disease processes that preferentially involve the fascia are also reviewed. PMID- 29791958 TI - Imaging Patterns of Muscle Atrophy. AB - The role of muscle imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI) is increasingly being used for diagnostic purposes, especially with its capability of whole-body musculature assessment. The assessment and quantification of muscle involvement in muscle diseases can be of diagnostic value by identifying a certain involvement pattern and thus narrowing the differential diagnosis and supporting the clinical diagnosis. In addition, more recently the role of imaging has gone beyond diagnostic purposes and includes disease as well as treatment monitoring. Conventional and quantitative muscle MRI techniques allow for the detection of subclinical disease progression (e.g., in muscular dystrophies) and is a powerful surrogate outcome measure in clinical trials. We present and discuss recent data on the role of conventional and quantitative MRI in the diagnosis and monitoring of inherited dystrophic muscle diseases as well as muscle denervation. PMID- 29791960 TI - Ultrasound of the Brachial Plexus. AB - Examination of the brachial plexus with ultrasound is efficient because it allows many parts of the brachial plexus as well as the surrounding soft tissues to be assessed with high spatial resolution. The key to performing good ultrasound of the brachial plexus is being familiar with the anatomy and the common variants. That makes it possible to concentrate solely on the ultrasound appearances free of simultaneously wondering about the anatomy. Ultrasound of the brachial plexus is particularly good for assessing nerve sheath tumor, perineural fibrosis, metastases, some inflammatory neuropathies, neuralgic amyotrophy, and posttraumatic sequalae. It is limited in the assessment of thoracic outlet syndrome and in the acute/subacute trauma setting. This review addresses the anatomy, ultrasound technique, as well as pathology of the brachial plexus from the cervical foramina to the axilla. PMID- 29791959 TI - Sarcopenia: Beyond Muscle Atrophy and into the New Frontiers of Opportunistic Imaging, Precision Medicine, and Machine Learning. AB - As populations continue to age worldwide, the impact of sarcopenia on public health will continue to grow. The clinically relevant and increasingly common diagnosis of sarcopenia is at the confluence of three tectonic shifts in medicine: opportunistic imaging, precision medicine, and machine learning. This review focuses on the state-of-the-art imaging of sarcopenia and provides context for such imaging by discussing the epidemiology, pathophysiology, consequences, and future directions in the field of sarcopenia. PMID- 29791961 TI - Getting Started with Magnetic Resonance Neurography. AB - This article provides a review of magnetic resonance neurography (MRN) and how to get started. It explains step by step how to establish MRN at an institution: how to set up MRN protocols, how to train technicians, what a report needs to contain, and how relevant findings should be communicated to the referring physician. Advanced imaging techniques such as diffusion tensor imaging are only briefly discussed at the end of the article because most of those techniques are difficult for beginners and are still not considered standard in the clinical routine. PMID- 29791962 TI - Nerve Entrapment Syndromes at the Wrist and Elbow by Sonography. AB - Nerve entrapment syndromes of the upper extremity are associated with structural abnormalities or by an intrinsic abnormality of the nerve. Nerve entrapment syndromes generally have a typical clinical presentation, and findings on physical examination and in conjunction with electrodiagnostic studies imaging is used to evaluate the cause, severity, and etiology of the entrapment. With the development of high-frequency linear array transducers (12-24 MHz), ultrasound (US) is incomparable in terms of spatial resolution to depict morphological aspects and changes in nerves. US can identify the abnormalities causing entrapment, such as fibrous bands, ganglia, anomalous muscles, and osseous deformities, with the advantage of dynamic assessment under active and passive examination. US is a unique diagnostic modality that allows superb visualization of both large and small peripheral terminal nerve branches of the upper extremity and enables the correct diagnosis of various nerve entrapment syndromes. PMID- 29791964 TI - Ultrasound-Guided Treatment of Peripheral Nerve Pathology. AB - High-resolution ultrasound serves as a fast, accessible, reliable, and radiation free tool for anatomical and dynamic evaluation of various peripheral nerves. It can be used not only to identify and diagnose peripheral nerve and perineural pathology accurately but also to guide various nerve and perineural interventions. We describe the normal and pathologic appearances of peripheral nerves, the pathologies commonly affecting the individual peripheral nerves, and the current ultrasound-guided peripheral nerve interventions and techniques. Future directions are also highlighted. PMID- 29791963 TI - Nerve Entrapment in Ankle and Foot: Ultrasound Imaging. AB - Peripheral nerve entrapment of the ankle and foot is relatively uncommon and often underdiagnosed because electrophysiologic studies may not contribute to the diagnosis. Anatomy of the peripheral nerves is variable and complex, and along with a comprehensive physical examination, a thorough understanding of the applied anatomy is essential. Several studies have helped identify specific areas in which nerves are commonly compressed. Identified secondary causes of nerve compression include previous trauma, osteophytes, ganglion cysts, edema, accessory muscles, tenosynovitis, vascular lesions, and a primary nerve tumor. Imaging plays a key role in identifying primary and secondary causes of nerve entrapment, specifically ultrasound (US) and magnetic resonance imaging. US is a dynamic imaging modality that is cost effective and offers excellent resolution. Symptoms of nerve entrapment may mimic other common foot and ankle conditions such as plantar fasciitis. PMID- 29791965 TI - Searching for non-transposable targets of planarian nuclear PIWI in pluripotent stem cells and differentiated cells. AB - Nuclear PIWIs together with their guide RNAs (piRNAs) epigenetically silence various genes including transposons in many organisms. In planarians, the nuclear piwi family gene, DjpiwiB is specifically transcribed in adult pluripotent stem cells (adult PSC, neoblast), but not in differentiated cells. However, the protein accumulates in the nuclei of both neoblasts and their descendant differentiated cells. Interestingly, PIWI(DjPiwiB)-piRNA complexes are indispensable for the repression of transposable genes at the onset of differentiation from neoblasts. Here, we conducted a comparative transcriptome analysis between control and DjpiwiB(RNAi) animals to identify non-transposable target genes of the DjPiwiB-piRNA complexes. Using bioinformatic analyses and RNAi we demonstrate that DjPiwiB-piRNA complexes are required for the proper expression of Djmcm2 and Djhistone h4 in neoblasts and that DjPiwiB-piRNA complexes regulate the transient expression of Djcalu during neoblast differentiation. Thus, DjPiwiB-piRNA complexes regulate the correct expression patterns during neoblast self-renewal and differentiation. PMID- 29791966 TI - Outcomes of Bethesda categories III and IV thyroid nodules over 5 years and performance of the Afirma gene expression classifier: A single-institution study. AB - OBJECTIVE: The second edition Bethesda System for Reporting Thyroid Cytology estimates 6%-18% malignancy rate of category III (B3) and 10%-40% for category IV (B4) nodules; however, reported malignancy rates have considerable variability among institutions. Use of molecular classifiers (including Afirma Gene Expression Classifier, GEC) can be utilized in management of thyroid nodules. Our objective was to analyse malignancy rates of B3 and B4 nodules and determine clinical outcomes of GEC Benign nodules. METHODS: A retrospective analysis of 2019 thyroid FNAs was performed at the University of Colorado from 2011 to 2015, including molecular, surgical and clinical follow-up. RESULTS: Of 2019 FNAs analysed, 231 (11.4%) were diagnosed as B3 and 80 (4.0%) as B4. GEC was obtained in 54.1% of B3 cases, with nearly half (48.8%) having a Benign result. Surgery was performed in 40.7% B3 cases with a 24.5% malignancy rate, ranging 8%-38% by year. In the B4 group, 52.5% underwent molecular testing with 28.6% as GEC Benign. About 68.8% of B4 cases underwent surgery with a 20% malignancy rate, ranging 0%-42% by year. Seventy-three GEC Benign cases were reviewed: 5 (6.8%) underwent surgery, with none demonstrating malignancy in the target nodule. Size remained stable for most GEC Benign nodules: 75.9% (B3) and 71.4% (B4) with no malignancy on repeat FNA. CONCLUSIONS: Our 5-year review demonstrated that malignancy rates of B3 and B4 nodules showed year-to-year variability. We suggest that clinicians use a multi-year average of their institution's malignancy rates to optimally manage patients. Follow-up for GEC Benign cases thus far supports their indolent nature. PMID- 29791968 TI - Multimodality treatment of hepatocellular carcinoma: How field practice complies with international recommendations. AB - BACKGROUND: Management of hepatocellular carcinoma (HCC) is framed within standardized protocols released by Scientific Societies, whose applicability and efficacy in field practice need refining. AIM: We evaluated the applicability and effectiveness of guidelines for the treatment of HCC of the American Association for the Study of the Liver (AASLD). METHODS: 370 consecutive cirrhotic patients with de novo HCC in different stages, 253 BCLC A, 66 BCLC B, 51 BCLC C received treatment through a multidisciplinary team (MDT) decision and were followed until death or end of follow-up. RESULTS: Treatment was adherent to AASLD recommendations in 205 (81%) BCLC A patients, 36 (54%) BCLC B, and 27 (53%) BCLC C. Radiological complete response was achieved in 165 (45%) patients after the first-line treatment, in 22 (19%) after a second-line and in 9 (23%) after a third-line treatment. Adherence to AASLD recommendation allowed a lower yearly mean mortality rate in BCLC A patients compared with other treatment (5.0% vs 10.4% P = .004), whereas upward treatment stage migration compared with the standard of care was associated with reduced yearly mortality in BCLC B (8.6% vs 20.7%, P = .029) and BCLC C (42.6% vs 59.0%, P = .04) patients. CONCLUSIONS: HCC multimodality treatment including other than first-line therapy is common in clinical practice and impact on the achievement of complete response. Personalized treatment was able to provide survival benefits to patients whose profile is not accounted for by international recommendations, which need to be amended. PMID- 29791967 TI - Global Emergency Medicine: A review of the literature from 2017. AB - OBJECTIVES: The Global Emergency Medicine Literature Review (GEMLR) conducts an annual search of peer-reviewed and gray literature relevant to global emergency medicine (EM) to identify, review, and disseminate the most important new research in this field to a global audience of academics and clinical practitioners. METHODS: This year, 17,722 articles written in three languages were identified by our electronic search. These articles were distributed among 20 reviewers for initial screening based on their relevance to the field of global EM. Another two reviewers searched the gray literature, yielding an additional 11 articles. All articles that were deemed appropriate by at least one reviewer and approved by their editor underwent formal scoring of overall quality and importance. Two independent reviewers scored all articles. RESULTS: A total of 848 articles met our inclusion criteria and underwent full review. 63% were categorized as emergency care in resource-limited settings, 23% as disaster and humanitarian response, and 14% as emergency medicine development. 21 articles received scores of 18.5 or higher out of a maximum score 20 and were selected for formal summary and critique. Inter-rater reliability testing between reviewers revealed a Cohen's Kappa of 0.344. CONCLUSIONS: In 2017, the total number of articles identified by our search continued to increase. Studies and reviews with a focus on infectious diseases, pediatrics, and trauma represented the majority of top-scoring articles. This article is protected by copyright. All rights reserved. PMID- 29791969 TI - Preparation of four 1,4-dihydropyridine derivatives (DHPs) labeled with carbon 14. AB - The importance of DHPs compounds and the need for examining the mechanism of their effect, mandated us to synthesize a number of carbon-14 labeled 1,4 dihydropyridine derivatives for pharmacological studies. Simple preparation and suitable radiochemical yield were advantages of this preparation. PMID- 29791970 TI - Effect of high-intensity resistance circuit-based training in hypoxia on aerobic performance and repeat sprint ability. AB - Recent acute studies have shown that high-intensity resistance circuit-based (HRC) training in hypoxia increases metabolic stress. However, no intervention studies have yet proven their effectiveness. This study aimed to analyze the effect of 8 weeks of HRC in hypoxia on aerobic performance, resting energy expenditure (REE), repeat sprint ability (RSA) and hematological variables. Twenty-eight subjects were assigned to hypoxia (FiO2 = 15%; HRChyp : n = 15; age: 24.6 +/- 6.8 years; height: 177.4 +/- 5.9 cm; weight: 74.9 +/- 11.5 kg) and normoxia (FiO2 = 20.9%; HRCnorm : n = 13; age: 23.2 +/- 5.2 years; height: 173.4 +/- 6.2 cm; weight: 69.4 +/- 7.4 kg) groups. Each training session consisted of two blocks of three exercises (Block 1: bench press, leg extension, front pull down; 2: deadlift, elbow flexion, ankle extension). Each exercise was performed at 6 repetitions maximum. Participants exercised twice weekly for 8 weeks and before and after the training program blood test, REE, RSA and treadmill running test were performed. Fatigue index in the RSA test was significantly decreased in the HRChyp (-0.9%; P < .01; ES = 2.75) but not in the HRCnorm . No changes were observed in REE and hematological variables. Absolute (4.5%; P = .014; ES = 0.42) and relative (5.2%; P = .008; ES = 0.43) maximal oxygen uptake (VO2 max), speed at VO2 max (4%; P = .010; ES = 0.25) and time to exhaustion (4.1%; P = .012; ES = 0.26) were significantly increased in HRChyp but not in the HRCnorm . No significant differences between groups were found. Compared with normoxic conditions, 8 weeks of HRC training under hypoxic conditions efficiently improves aerobic performance and RSA without changes in REE and red blood O2 -carrying capacity. PMID- 29791972 TI - Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis. AB - Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the thoracic and abdominal organs. Many intra-abdominal and vessel anomalies have been reported in association with SIT. However, there have been no reports on the use of laparoscopic radical nephrectomy with thrombectomy for renal vein thrombus, which is considered as a safe and feasible procedure, in patients with SIT. We herein present the case of an 80-year-old man with SIT who was preoperatively diagnosed with a right renal tumor and renal vein tumor thrombus. The patient underwent laparoscopic right nephrectomy and tumor thrombectomy with no intraoperative complications. To ensure a safe procedure, the anatomy and vessels were carefully evaluated preoperatively using 3-D multiplanar reconstructed CT imaging. Assessing anatomical structures leads to safer laparoscopic radical nephrectomy for renal cell carcinoma with venous tumor thrombus in patients with SIT. PMID- 29791971 TI - Predictors of treatment success after collagenase Clostridium histolyticum injection for Peyronie's disease: development of a nomogram from a multicentre single-arm, non-placebo controlled clinical study. AB - OBJECTIVE: To build a nomogram able to predict treatment success after collagenase Clostridium histolyticum (CCH) for Peyronie's disease (PD). MATERIALS AND METHODS: Between November 2016 and November 2017, we enrolled 135 patients with PD into a multicentre single-arm prospective study. All patients enrolled received CCH treatment. Success of therapy was defined as a decrease in penile curvature (PC) of >=20 degrees from baseline. Treatment satisfaction was assessed using a scale from 1 to 10, and high satisfaction was arbitrarily defined as a score of >=8. Calcification level was classified as: absence of calcification; low perilesional calcification; and high calcification. RESULTS: The median (interquartile range [IQR]) patient age was 56.0 (45.0-65.0) years and the median (IQR) was PC was 30 (30.0-60.0) degrees . After the treatment protocol, we observed a significant median change in PC of -20.0 degrees (P < 0.01). The median (IQR) PC improvement was 44 (28.0-67.0)%. Overall median (IQR) satisfaction score was 8.0 (7.0-9.0). Treatment efficacy was reported in a total of 77 patients (57.04%). When analysing factors associated with PC improvement after treatment, we found that baseline PC (odds ratio [OR] 1.14; P < 0.01), basal plaque (OR 64.27; P < 0.01), low calcification (OR 0.06; P < 0.01) and high calcification (OR 0.03; P < 0.01) were significant predictors of PC improvement. The c-index for the model was 0.93. CONCLUSIONS: Patients with longer PD duration, greater baseline PC and basal plaque location had a greater chance of treatment success. These results could be applied to clinical practice before external validation of our nomogram. PMID- 29791973 TI - A forbidden topic at the end of life: "What about you after I'm gone?" PMID- 29791974 TI - Isolation and identification of Vibrio species in the Rio Bravo/Grande and water bodies from Reynosa, Tamaulipas. AB - : The Rio Bravo (Rio Grande) adjoins various states in the Mexican region and has a great importance in water distribution in the northeast Tamaulipas (Mexico). In this work 161 strains were isolated, identified and characterized from the water samples taken from the flow of the Rio Bravo and the two inner canals that cover Reynosa city. The strains were identified as Vibrio cholerae (74.5%), Vibrio spp. (1.2%) and Vibrio mimicus (0.6%). Furthermore, the detected virulence genes in the V. cholerae strains, were the hlyA, ompU, tcpA, toxR genes in 78.3, 62.5, 15.8 and 90.8% respectively. Only the ompU and vmh genes were detected in the V. mimicus strain. These results indicate the presence of multi-toxigenic V. cholerae strains in the Rio Bravo/Grande and in the water bodies from Reynosa city, which could represent a risk for the exposed population. SIGNIFICANCE AND IMPACT OF THE STUDY: Water quality is associated with public health, as it plays an important role in the transmission and epidemiology of pathogens such as Vibrio, since this species have been responsible for human diseases around the world. This study demonstrated the presence of toxigenic Vibrio species in water bodies in Reynosa surroundings, indicating that water bodies may be a source of public health risk. PMID- 29791975 TI - CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma. AB - BACKGROUND: Tumour metastasis has been associated with cancer stem cells, a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to cells from the tumour bulk. Our aim was to evaluate the immunoexpression of the putative cancer stem cell biomarkers ALDH1 and CD44 in primary tumour and corresponding metastatic lymph nodes. METHODS: Tumour tissue specimens (n = 50) and corresponding metastatic lymph nodes (n = 25) were surgically obtained from 50 patients with oral squamous cell carcinoma and submitted to immunohistochemistry. CD44 and ALDH1 were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic lymph nodes as a whole. A combined score was obtained by multiplying both parameters and later dichotomized into a final score classified as low (<=2) or high (>2) immunoexpression. RESULTS: ALDH1 immunoexpression and CD44 immunoexpression were detected in both tumour sites, although the means of ALDH1 (P = .0985) and CD44 (P = .4220) cells were higher in metastasis compared to primary tumours. ALDH1high was positively associated (P = .0184) with angiolymphatic invasion, while CD44high was positively associated (P = .0181) with metastasis (N+). At multivariate analysis, CD44 significantly increased the odds of lymph node metastasis, regardless of T stage (OR = 8.24; 1.64-65.64, P = .0088). CONCLUSIONS: CD44 immunoexpression was a significant predictor of lymph node metastasis, while ALDH1high immunostaining was associated with angiolymphatic invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with oral squamous cell carcinoma invasion and metastasis. PMID- 29791976 TI - A CIPK protein kinase targets sucrose transporter MdSUT2.2 at Ser254 for phosphorylation to enhance salt tolerance. AB - Soil salinity is one of the major abiotic stressors that negatively affect crop growth and yield. Salt stress can regulate antioxidants and the accumulation of osmoprotectants. In the study, a sucrose transporter MdSUT2.2 was identified in apple. Overexpression of MdSUT2.2 gene increased salt tolerance in the transgenic apple, compared with the WT control "Gala." In addition, it was found that protein MdSUT2.2 was phosphorylated at Ser254 site in response to salt. A DUAL membrane yeast hybridization system through an apple cDNA library demonstrated that a protein kinase MdCIPK13 interacted with MdSUT2.2. A series of transgenic analysis in apple calli showed that MdCIPK13 was required for the salt-induced phosphorylation of MdSUT2.2 protein and enhanced its stability and transport activity. Finally, it was found that MdCIPK13 improved salt resistance in an MdSUT2.2-dependent manner. These findings had enriched our understanding of the molecular mechanisms underlying abiotic stress. PMID- 29791977 TI - No association between rate of torque development and onset of muscle activity with increased risk of hamstring injury in elite football. AB - Hamstring injuries remain a significant burden in sports that involve high-speed running. In elite male football, hamstring injury has repeatedly been identified as the most common non-contact injury, representing 12% of all injuries. As the incidence remains high, investigations are aimed at better understanding how to improve prevention efforts. Intrinsic risk factors such as strength have been investigated extensively in a cohort of professional football players; however, other intrinsic measures of neuromuscular function have not been studied in this cohort. This study aims to investigate the association between timing of hamstring muscle activity onset and the rate of torque development during the early phase of isokinetic strength testing with risk of hamstring injury in professional football players in a prospective cohort study. All teams (n = 18) eligible to compete in the premier football league in Qatar underwent a comprehensive strength assessment during their annual periodic health evaluation at Aspetar Orthopaedic and Sports Medicine Hospital in Doha, Qatar. Variables included rate of torque development and timing of muscle activity onset. A total of 367 unique players (60.6% of all QSL players) competed for 514 player seasons (103 players competed both seasons) and sustained 65 hamstring injuries. There was no difference in the onset of muscle activity between the biceps femoris and medial hamstrings comparing the injured to uninjured players. For both onset of muscle activity and rate of torque development, there were no significant differences between any of the variables (P > .05), with small effect sizes detected across all the different variables (d < 0.3). Rate of torque development and onset of muscle activity were not associated with a risk of future hamstring injury. The use of these measures as part of a periodic health evaluation to identify risk of hamstring injury is unsupported. PMID- 29791978 TI - Combination of endoscopic submucosal dissection and transanal minimally invasive surgery for the resection of early rectal cancer with fibrosis after prior partial excision. AB - Endoscopic submucosal dissection is an effective procedure for treating non invasive colorectal tumors. However, in cases of severe fibrosis, endoscopic submucosal dissection may be technically difficult, leading to incomplete resection. Here, we describe the case of a 74-year-old man who had early rectal cancer along with severe submucosal fibrosis caused by prior local excision. Combination treatment with endoscopic submucosal dissection and transanal minimally invasive surgery successfully enabled complete resection. PMID- 29791980 TI - Pulmonary artery dissection caused by extension of acute type B aortic dissection through the ductus arteriosus. PMID- 29791981 TI - Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report. AB - We report herein a patient with an inguinoscrotal hernia containing the urinary bladder. The hernia was safely repaired using the laparoscopic transabdominal preperitoneal repair technique. A 76-year-old man was admitted to our hospital with abdominal pain, vomiting, and diarrhea. His scrotum was swollen to fist size. Abdominal CT showed herniation of the sigmoid colon and the bladder into the right inguinal region, and his abdominal pain was attributed to incarceration of the sigmoid colon; this was manually reduced. About 1 month later, we performed transabdominal preperitoneal repair. After the direct hernial orifice was identified, the bladder was noted to be sliding from the medial side of the hernia; this was reduced. Peeling on the medial side was carried out to the middle of the abdominal wall, and the myopectineal orifice was covered with mesh. The patient was discharged on postoperative day 1. PMID- 29791983 TI - [Management of Gallstone]. AB - Gallstones are one of the most common diseases worldwide. Recently, the incidence of gallstones has increased and the pattern of gallstones has changed in Korea. Laparoscopic cholecystectomy is the standard treatment for symptomatic gallstones. Expectant management is considered the most appropriate choice in patients with asymptomatic gallstones. The dissolution of cholesterol gallstones by oral bile acid, such as ursodeoxycholic acid, can be considered in selected patients with gallstones. Although the advent of laparoscopic cholecystectomy has moved interest away from the pharmacologic treatment of gallstones, several promising agents related to various mechanisms are under investigation. PMID- 29791982 TI - [Management of Intrahepatic Duct Stone]. AB - Intrahepatic duct (IHD) stone is the presence of calculi within the intrahepatic bile duct specifically located proximal to the confluence of the left and right hepatic ducts. This stone is characterized by its intractable nature and frequent recurrence, requiring multiple therapeutic interventions. Without proper treatment, biliary strictures and retained stones can lead to repeated episodes of cholangitis, liver abscesses, secondary biliary cirrhosis, portal hypertension, and death from sepsis or hepatic failure. The ultimate treatment goals for IHD stones are complete removal of the stone, the correction of the associated strictures, and the prevention of recurrent cholangitis. A surgical resection can satisfy the goal of treatment for hepatolithiasis, i.e., complete removal of the IHD stones, stricture, and the risk of cholangiocarcinogenesis. On the other hand, in some cases, such as bilateral IHD stones, surgery alone cannot achieve these goals. Therefore, the optimal treatments require a multidisciplinary approach, including endoscopic and radiologic interventional procedures before and/or after surgery. Percutaneous transhepatic cholangioscopic lithotomy (PTCS-L) is particularly suited for patients at poor surgical risk or who refuse surgery and those with previous biliary surgery or stones distributed in multiple segments. PTCS-L is relatively safe and effective for the treatment of IHD stones, and complete stone clearance is mandatory to reduce the sequelae of IHD stones. An IHD stricture is the main factor contributing to incomplete clearance and stone recurrence. Long-term follow-up is required because of the overall high recurrence rate of IHD stones and the association with cholangiocarcinoma. PMID- 29791984 TI - [The Management of Common Bile Duct Stones]. AB - Common bile duct (CBD) stone is a relatively frequent disorder with a prevalence of 10-20% in patients with gallstones. This is also associated with serious complications, including obstructive jaundice, acute suppurative cholangitis, and acute pancreatitis. Early diagnosis and prompt treatment is the most important for managing CBD stones. According to a recent meta-analysis, endoscopic ultrasonography and magnetic resonance cholangiopancreatography have high sensitivity, specificity, and accuracy for the diagnosis of CBD stones. Endoscopic ultrasonography, in particular, has been reported to have higher sensitivity between them. A suggested management algorithm for patients with symptomatic gallstones is based on whether they are at low, intermediate, or high probability of CBD stones. Single-stage laparoscopic CBD exploration and cholecystectomy is superior to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy with respect to technical success and shorter hospital stay in high risk patients with gallstones and CBD stones, where expertise, operative time, and instruments are available. ERCP plus laparoscopic cholecystectomy is usually performed to treat patients with CBD stones and gallstones in many institutions. Patients at intermediate probability of CBD stones after initial evaluation benefit from additional biliary imaging. Patients with a low probability of CBD stones should undergo cholecystectomy without further evaluation. Endoscopic sphincterotomy and endoscopic papillary balloon dilation in ERCP are the primary methods for dilating the papilla of Vater for endoscopic removal of CBD stones. Endoscopic papillary large balloon dilation is now increasingly performed due to the usefulness in the management of giant or difficult CBD stones. Scheduled repeated ERCP may be considered in patients with high risk of recurrent CBD stones. PMID- 29791979 TI - Functional and structural characterization of zebrafish ASC. AB - : The zebrafish genome encodes homologs for most of the proteins involved in inflammatory pathways; however, the molecular components and activation mechanisms of fish inflammasomes are largely unknown. ASC [apoptosis-associated speck-like protein containing a caspase-recruitment domain (CARD)] is the only adaptor involved in the formation of multiple types of inflammasomes. Here, we demonstrate that zASC is also involved in inflammasome activation in zebrafish. When overexpressed in vitro and in vivo in zebrafish, both the zASC and zASC pyrin domain (PYD) proteins form speck and filament structures. Importantly, the crystal structures of the N-terminal PYD and C-terminal CARD of zebrafish ASC were determined independently as two separate entities fused to maltose-binding protein. Structure-guided mutagenesis revealed the functional relevance of the PYD hydrophilic surface found in the crystal lattice. Finally, the fish caspase-1 homolog Caspy, but not the caspase-4/11 homolog Caspy2, interacts with zASC through homotypic PYD-PYD interactions, which differ from those in mammals. These observations establish the conserved and unique structural/functional features of the zASC-dependent inflammasome pathway. DATABASE: Structural data are available in the PDB under accession numbers 5GPP and 5GPQ. PMID- 29791985 TI - [Management of Acute Cholecystitis]. AB - Acute cholecystitis is a common serious complication of gallstones. The reported mortality of acute cholecystitis is approximately 3%, but the rate increases with age or comorbidity of the patient. If appropriate treatment is delayed, complications can develop as a consequence with a grave prognosis. The current standard of care in acute cholecystitis is an early laparoscopic cholecystectomy with the appropriate administration of fluid, electrolyte, and antibiotics. On the other hand, the severity of the disease and patient's operational risk must be considered. In those with high operational risks, gall bladder drainage can be performed as an alternative. Currently percutaneous and endoscopic drainage are available and show clinical success in most cases. After recovering from acute cholecystitis, the patients who have undergone drainage should be considered for cholecystectomy as a definitive treatment. However, in elderly patients or patients with significant comorbidity, operational risks may still be high, making cholecystectomy inappropriate. In these patients, gallstone removal using the percutaneous tract or endoscopy may be considered. PMID- 29791986 TI - [Revision of Quality Indicators for the Endoscopy Quality Improvement Program of the National Cancer Screening Program in Korea]. AB - Gastroscopy and colonoscopy are widely used for the early diagnosis of stomach and colorectal cancer. The present revision integrates recent data regarding previous quality indicators and novel indicators suggested for gastroscopy and colonoscopy procedures for the National Cancer Screening Program in Korea. The new indicators, developed by the Quality Improvement Committee of the Korean Society for Gastrointestinal Endoscopy, vary in the level of supporting evidence, and most are based solely on expert opinion. Updated indicators validated by clinical research were prioritized, but were chosen by expert consensus when such studies were absent. The resultant quality indicators were graded according to the levels of consensus and recommendations. The updated indicators will provide a relevant guideline for high-quality endoscopy. The future direction of quality indicator development should include relevant outcome measures and an evidence based approach to support proposed performance targets. PMID- 29791987 TI - [Management of Patients on Antithrombotic Agents Undergoing Endoscopy]. AB - Antithrombotic agents are used increasingly in Asia. The management of patients on antithrombotics undergoing elective or emergency endoscopy has become an increasing clinical challenge for gastroenterologists. Current practice guidelines have been developed by societies from western countries. On the other hand, these guidelines cannot meet the specific needs of the Asian Pacific region, raising the need for separate guidelines in Asia. This review compares the recommendations of previous guidelines with the most recently published Asian guidelines regarding the management of patients on antithrombotic agents undergoing elective and emergency endoscopy. PMID- 29791988 TI - [Liver Abscess Secondary to Perforation after Duodenal Endoscopic Resection]. AB - Duodenal perforation is a complication of endoscopic mucosal resection. Liver abscess secondary to iatrogenic perforation is extremely rare. A 43-year-old female visited the hospital to remove a sub-epithelial tumor on the duodenal bulb. After endoscopic mucosal resection with band ligation, duodenal perforation occurred. Endoscopic closure was performed successfully using a clipping device to manage duodenal perforation. After 4 weeks, the patient visited our outpatient clinic due to abdominal pain and fever. Abdominal computed tomography showed liver abscess that involved segment three. Liver abscess was resolved with a 10 week antibiotic treatment. To the best of our knowledge, no case of liver abscess secondary to duodenal perforation by endoscopic resection was reported to date in Korea. Here, we report a case of liver abscess caused by a duodenal perforation after endoscopic mucosal resection. PMID- 29791989 TI - An Unexpected Adverse Event during Colonoscopy Screening: Bochdalek Hernia. AB - Bochdalek hernia (BH) is defined as herniated abdominal contents appearing throughout the posterolateral segment of the diaphragm. It is usually observed during the prenatal or newborn period. Here, we report a case of an adult patient with herniated omentum and colon due to BH that was discovered during a colonoscopy. A 41-year-old woman was referred to our hospital with severe left chest and abdominal pain that began during a colonoscopy. Her chest radiography showed colonic shadow filling in the lower half of the left thoracic cavity. A computed tomography scan revealed an approximately 6-cm-sized left posterolateral diaphragmatic defect and a herniated omentum in the colon. The patient underwent thoracoscopic surgery, during which, the diaphragmatic defect was closed and herniated omentum was repaired. The patient was discharged without further complications. To the best of our knowledge, this case is the first report of BH in an adult found during a routine colonoscopy screening. PMID- 29791990 TI - Annular Pancreas in Adult. PMID- 29791991 TI - The Role of Serum HBV-RNA Levels as a Marker of Intrahepatic Viral and Histologic Activity. PMID- 29791993 TI - Rate Constant for the Recombination Reaction CH3 + CH3 -> C2H6 at T = 298 and 202 K. AB - The recombination of methyl radicals is the major loss process for methyl in the atmospheres of Saturn and Neptune. The serious disagreement between observed and calculated levels of CH3 has led to suggestions that the atmospheric models greatly underestimated the loss of CH3 due to poor knowledge of the rate of the reaction CH3 + CH3 + M -> C2H6 + M at the low temperatures and pressures of these atmospheric systems. In an attempt to resolve this problem, the absolute rate constant for the self-reaction of CH3 has been measured using the discharge-flow kinetic technique coupled to mass spectrometric detection at T = 202 and 298 K and P = 0.6-2.0 Torr nominal pressure (He). CH3 was produced by the reaction of F with CH4, with [CH4] in large excess over [F], and detected by low energy (11 eV) electron impact ionization at m/ z = 15. The results were obtained by graphical analysis of plots of the reciprocal of the CH3 signal vs reaction time. At T = 298 K, k 1(0.6 Torr) = (2.15 +/- 0.42) * 10-11 cm3 molecule-1 s-1 and k 1(1 Torr) = (2.44 +/- 0.52) * 10-11 cm3 molecule-1 s-1. At T = 202 K, the rate constant increased from k 1(0.6 Torr) = (5.04 +/- 1.15) * 10-11 cm3 molecule-1 s-1 to k 1(1.0 Torr) = (5.25 +/- 1.43) * 10-11 cm3 molecule-1 s-1 to k 1(2.0 Torr) = (6.52 +/- 1.54) * 10-11 cm3 molecule-1 s-1, indicating that the reaction is in the falloff region. Klippenstein and Harding had previously calculated rate constant falloff curves for this self-reaction in Ar buffer gas. Transforming these results for a He buffer gas suggest little change in the energy removal per collision, -d, with decreasing temperature and also indicate that d for He buffer gas is approximately half of that for Argon. Since the experimental results seem to at least partially affirm the validity of the Klippenstein and Harding calculations, we suggest that, in atmospheric models of the outer planets, use of the theoretical results for k 1 is preferable to extrapolation of laboratory data to pressures and temperatures well beyond the range of the experiments. PMID- 29791994 TI - Letter to the Editor Regarding "Optical Coherence Tomography in the Management of Skull Base Fibrous Dysplasia with Optic Nerve Involvement". PMID- 29791992 TI - Role of the Duodenum in the Pathogenesis of Functional Dyspepsia: A Paradigm Shift. AB - Functional dyspepsia (FD) is a common disorder characterized by chronic epigastric pain or burning, or bothersome postprandial fullness or early satiation, without a definitive organic cause. The pathogenesis of FD is likely heterogeneous. Classically, motor disorders, visceral hypersensitivity, and brain gut interactions have been implicated in the pathophysiology of FD, but recently an important role for chronic low-grade inflammation and infection in FD has been reported and confirmed. Duodenal low-grade inflammation is frequently observed in FD in those with and without documented previous gastroenteritis. Duodenal eosinophils and in some cases mast cells may together or separately play a key role, and immune activation (eg, circulating homing small intestinal T cells) has been observed in FD. Low-grade intestinal inflammation in patients with FD may provoke impairment in motor-sensory abnormalities along the gastrointestinal neural axis. Among FD patients, the risk of developing dyspeptic symptoms after a bout of gastroenteritis is 2.54 (95% CI, 1.76-3.65) at more than 6 months after acute gastroenteritis. Gut host and microbial interactions are likely important, and emerging data demonstrate both quantitative and qualitative changes of duodenal mucosal and fecal microbiota in FD. Food antigens (eg, wheat proteins) may also play a role in inducing duodenal inflammation and dyspepsia. While causation is not established, the hypothesis that FD is a disorder of microscopic small intestinal inflammation in a major subset is gaining acceptance, opening the possibility of novel treatment approaches that may be able to alter the natural history of the disorder. PMID- 29791995 TI - Letter to the Editor Regarding "Minimally Invasive Alternative Approaches to Pterional Craniotomy: A Systematic Review of the Literature". PMID- 29791997 TI - Letter to the Editor Regarding "Rupture Risk of Cerebral Arteriovenous Malformations During Pregnancy and Puerperium: A Single-Center Experience and Pooled Data Analysis". PMID- 29791996 TI - Do Gliomas Behave Differently in Patients with Human Immunodeficiency Virus? PMID- 29791998 TI - Discussion on the Hemorrhagic Risk of Female AVM Patients During Their Pregnancy and Puerperium Periods. PMID- 29791999 TI - Full Endoscopic Vascular Decompression: Is It What We Should Aim for? PMID- 29792000 TI - Endoscopic Microvascular Decompression for Trigeminal Neuralgia: Is It What We Should Aim for? PMID- 29792001 TI - Epistemology and the World of Neurosurgery Research. PMID- 29792002 TI - Emergence of multi-drug resistant Salmonella. PMID- 29792003 TI - Rheumatic heart disease: Strategies for prevention and control. PMID- 29792005 TI - Immunodiagnosis in osteoarticular tuberculosis by ELISA. AB - BACKGROUND: It was previously difficult to confirm a clinical diagnosis of tuberculosis by a cheap test, but recently ELISA for circulating antibodies has been found to be reliable in certain cases. We have used this test in osteoarticular tuberculosis. METHODS: We studied 50 patients with the disease (34 confirmed by biopsy and 16 who responded to chemotherapy) and compared them with 50 matched control subjects. ELISA was performed using Antigen 60-a cell wall cytoplasmic antigen of Mycobacterium tuberculosis. RESULTS: The test was positive in 27 out of 34 biopsy proven cases, 11 out of 16 patients who responded to chemotherapy and in only 1 out of 50 control subjects. CONCLUSIONS: ELISA using Antigen 60 may be a useful confirmatory test for osteoarticular tuberculosis. PMID- 29792004 TI - A rheumatic fever and rheumatic heart disease control programme in a rural community of north India. AB - BACKGROUND: This study was conducted in a rural community of north India to evaluate a rheumatic fever and rheumatic heart disease control programme which used the existing health and educational infrastructure. METHODS: A health education campaign was launched in a rural community block (population 140 000) with a similar non-contiguous block (population 180 000) serving as a control. In the intervention block, 74 primary health workers, 773 teachers and 12 500 students were trained to suspect the disease. Twelve medical officers in four health centres registered patients, who were put on secondary prophylaxis with penicillin or sulphonamide, and monitored their compliance. All the cases were examined by a cardiologist to confirm the diagnosis; if the diagnosis was not confirmed secondary prophylaxis was stopped. RESULTS: In the two years preceding intervention, 13 cases (case detection rate 3.6/100 000 population/year) were detected from the health centre records in the control and 22 (7.8/100 000/year) from the intervention block. During the two years of study 16 new cases (4.4/100 000/year) were registered in the control block whereas 254 suspected cases of rheumatic fever and rheumatic heart disease were referred to medical officers in the intervention block. Of these, 77 new cases (27.5/100 000/year) were registered, of which 61 (79%) were subsequently confirmed to have the disease- 48 had chronic rheumatic disease and 13 their first attack of acute rheumatic fever. Secondary prophylaxis in the form of penicillin or sulphonamide was instituted in these patients with a compliance of 85% to 95%. CONCLUSIONS: In developing countries, it is possible to successfully apply a secondary prevention programme for the early detection of rheumatic fever and rheumatic heart disease using existing primary health care auxiliaries, school teachers and pupils at an affordable additional cost. PMID- 29792006 TI - Antisense molecular biology. PMID- 29792008 TI - Bombay's kidney commerce and Arab patients. PMID- 29792007 TI - Haematopoietic growth factors. PMID- 29792009 TI - Lymphocytes and gene therapy. PMID- 29792010 TI - Stress and the Blood-Brain Barrier. PMID- 29792011 TI - How to evaluate causation. PMID- 29792012 TI - Peripheral blood smear. PMID- 29792013 TI - Purchasing expensive medical equipment. PMID- 29792015 TI - Acquisition of spongiform encephalo-pathies in India through sheep-brain rabies vaccination. PMID- 29792014 TI - Letter from London. PMID- 29792016 TI - Erratum PMID- 29792017 TI - Correlations of serum cystatin C and hs-CRP with vascular endothelial cell injury in patients with active systemic lupus erythematosus. AB - BACKGROUND: To investigate the correlations of serum cystatin C and high sensitivity C-reactive protein (hs-CRP) with vascular endothelial cell injury in patients with active systemic lupus erythematosus (SLE). METHODS: A total of 80 patients with SLE treated in our hospital from January 2016 to September 2017 were selected and randomly divided into stable-stage group (n=40) and active stage group (n=40) using a random number table. The expressions of cystatin C and hs-CRPin stable and active stages were compared, and the inner diameters of brachial artery and levels of vascular endothelial growth factors in stable and active stages were also compared.The correlationsof expressions of cystatin C and hs-CRP in active stage with the inner diameter of brachial artery and vascular endothelial growth factor were analyzed. At the same time, the correlation between vascular endothelial growth factor and inner diameter of brachial artery in active stage was analyzed. RESULTS: The level of cystatin C in active stage was higher than that in stable stage (P<0.05), and the expression level of hs-CRP in active stage was also higher than that in stable stage (P<0.05). The inner diameter of brachial artery in active stage was smaller than that in stable stage (P<0.05), butthe level of vascular endothelial growth factor was higher than that in stable stage (P<0.05). The expressions of cystatin C and hs-CRP were negatively correlated with the inner diameter of brachial artery in active stage (P<0.05). The expressions of cystatin C and hs-CRP were positively correlated with vascular endothelial growth factor in active stage (P<0.05). Moreover, there was a negative correlation between vascular endothelial growth factor and inner diameter of brachial artery in active stage (P<0.05). CONCLUSIONS: Levels of cystatin C and hs-CRP are significantly increased in patients with active SLE, and the increase degrees are negatively correlated with the inner diameter of brachial artery under ultrasound, but positively correlated with the level of vascular endothelial growth factor in vivo. PMID- 29792018 TI - Predictive factors of a poor outcome following revascularization for critical limb ischemia: implications for practice. AB - BACKGROUND: Advancements in open and endovascular techniques have brought a widespread indication of revascularization in the majority of patients with critical limb ischemia (CLI). However, some cases still have a dismal short-term outcome. Identifying preoperative variables that characterize these patients could be important to prevent futile decisions. The aim of this study was to define predictive risk factors of mortality and/or major amputation after revascularization for CLI. METHODS: Retrospective study of 515 consecutive patients (mean age=73 years; 73% males) undergoing open (N.=228; 44.3%) or endovascular (N.=287; 55.7%) surgery for CLI between 2005 and 2015. Neither redo procedures (ipsilateral or contralateral) nor acute limb ischemia patients were included as new cases. RESULTS: Thirty-day amputation, mortality or combined event rates were 1.4% (N.=7), 4.5% (N.=23) and 5.6% (N.=29), while at 90 days were 4.1 (N.=21), 9.1% (N.=47) and 12.8% (N.=66), respectively. We found no significant differences between open or endovascular surgery. Risk factors associated with a 90-day combined event were age (OR=1.04, P=0.014), preoperative hemoglobin (OR=0.80; P=0.003), history of acute myocardial infarction (OR=2.68; P=0.007), ischemic ulcers (OR=2.57; P=0.014) and below-the-knee revascularization (OR=2.20; P=0.007). The discrimination of the model was good (area under ROC curve=0.75). Model predicted probabilities of the combined death and/or lower limb major amputation end-point ranged (95% interval) from 1.1% to 38.1%. CONCLUSIONS: Certain preoperative variables can predict satisfactorily the short term outcome after revascularization for CLI, although they are not sufficiently useful to identify the patient in whom revascularization can be clearly futile. Further research is needed to refine a predictive model suitable for decision making. PMID- 29792019 TI - Alcohol use disorders, cardiomyopathy and heart transplantation: a new management. PMID- 29792020 TI - Daclatasvir and asunaprevir combination therapy for patients with chronic hepatitis C virus genotype 1b infection in real world. AB - Background/Aims: Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world. Methods: We enrolled 278 patients (184 treatment-naive patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure. Results: The mean age of patients was 59.5 +/- 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure. Conclusions: DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events. PMID- 29792021 TI - Evaluation of tooth discoloration after the use of experimental medication as root canal dressings: an in vitro study. AB - BACKGROUND: Endodontic infections require the use of root canal dressings to reduce microorganisms, and studies of new intracanal medications are common. Two experimental intracanal medications that contain antibiotics and chlorhexidine have been proposed. However, given the composition of these medications, tooth discoloration with subsequent impacts on aesthetic parameters is a concern. The objective of this study is to evaluate tooth discoloration after the use of experimental intracanal medications for up to 180 days. METHODS: Thirty extracted bovine teeth were divided into 3 groups according to intracanal medication as follows: group I: experimental intracanal medication 1; group II: experimental intracanal medication 2; and group III: no medication (negative control). Color change was assessed using a spectrophotometer on day 0 (before the placement of the material); daily until the seventh day; and 8, 15, 60 and 180 days after removal of the medications. The values obtained were compared using ANOVA and Tukey's tests at a significance level of 5% (P<0.05). RESULTS: Up to 60 days after the removal of the medication, the teeth did not exhibit color changes. However, at 180 days, compared with the other medications, experimental intracanal medication 2 significantly promoted tooth staining (P<0.05). CONCLUSIONS: In contrast to experimental intracanal medication 2, intracanal medication 1 did not promote tooth discoloration. PMID- 29792022 TI - Bidirectional Synthesis of Di- tert-butyl (2 S,6 S,8 S)- and (2 R,6 R,8 R)-1,7 Diazaspiro[5.5]undecane-2,8-dicarboxylate and Related Spirodiamines. AB - Efficient syntheses of both enantiomers of a spirodiamine diester from (l)- and (d)-aspartic acid are described. The key transformation was the conversion of Boc protected tert-butyl aspartate into the derived aldehyde, two-directional Horner Wadsworth-Emmons olefination, hydrogenation, and selective acid-catalyzed Boc deprotection and spirocyclization. An alternative, two-directional approach to derivatives of 1,7-diazaspiro[5.5]undecane is described. PMID- 29792023 TI - Fern-9(11)-ene-2alpha,3beta-diol Action on Insulin Secretion under Hyperglycemic Conditions. AB - The objective of this study was to investigate the effect and the mechanism of action of fernenediol as an insulin secretagogue. Wistar rats were treated with 0.1, 1, and 10 mg/kg fernenediol before inducing hyperglycemia by oral glucose. The glycaemia, insulin, LDH, calcium, and hepatic glycogen were analyzed. Considering the intestine and pancreas as targets for the triterpene action, the duodenum was used to verify the influence of fernenediol on intestinal glycosidases. Additionally, pancreatic islets were used for studies of 14C deoxyglucose uptake and the influx of 45Ca2+ in hyperglycemic media with/without fernenediol in the presence/absence of an inhibitor/activator of KATP channels, glibenclamide, diazoxide, nifedipine, calcium chelator (BAPTA-AM), and H-89 and ST, the inhibitors of the PKA and PKC enzymes. Fernenediol significantly reduced glycaemia, potentiated glucose-induced insulin secretion, and stimulated liver glycogen deposition in hyperglycemic rats after an in vivo treatment without changing intestinal disaccharidases activities and showing no influence on intestinal glucose absorption. Also, it stimulated the glucose uptake and calcium influx in pancreatic islets. The involvement of voltage-dependent L-type calcium channels and ATP-dependent potassium channels and the release of calcium from intracellular stores are mandatory for the stimulatory effect of fernenediol on calcium influx. Fernenediol did not change PKA and PKC activities or modify calcium levels. This triterpene is a potent antihyperglycemic agent with a strong insulin secretagogue effect on glycogen accumulation as well. As a whole, this compound presents significant perspectives as a future new drug for the treatment of insulin resistance and/or diabetes. PMID- 29792025 TI - Hierarchical Nanostructures of Nitrogen-Doped Porous Carbon Polyhedrons Confined in Carbon Nanosheets for High-Performance Supercapacitors. AB - Interconnected close-packed nitrogen-doped porous carbon polyhedrons (NCPs) confined in two-dimensional carbon nanosheets (CNSs) have been prepared through a sustainable one-pot pyrolysis of a simple solid mixture of zeolitic imidazolate framework-8 (ZIF-8) crystals and with organic potassium as the precursors. The hierarchically organized framework of the NCP-CNS composites enables NCPs and CNSs to act as well-defined electrolyte reservoirs and mechanical buffers accommodating large volume expansions of NCPs, respectively. Among the unique composite nanostructures, the NCPs with vast micropores provide electric double layer capacitances, while the CNSs bridge the individual NCPs to form a conductive pathway with a hierarchical porosity. As a result, the NCP-CNS composites with high electrical integrity and structural stability are used as electrode materials for high-performance supercapacitors, which exhibit excellent electrochemical capacitive characteristics in terms of an outstanding capacitance of 300 F g-1 at 1 A g-1, large energy density of 20.9 W h kg-1, and great cycling performance of 100% retention after 6000 cycles. This work therefore presents a one-pot and efficient strategy to prepare an ordered arrangement of ZIF-8-derived porous carbons toward new electrode materials in promising energy storage systems. PMID- 29792026 TI - CO-Bridged H-Cluster Intermediates in the Catalytic Mechanism of [FeFe] Hydrogenase CaI. AB - The [FeFe]-hydrogenases ([FeFe] H2ases) catalyze reversible H2 activation at the H-cluster, which is composed of a [4Fe-4S]H subsite linked by a cysteine thiolate to a bridged, organometallic [2Fe-2S] ([2Fe]H) subsite. Profoundly different geometric models of the H-cluster redox states that orchestrate the electron/proton transfer steps of H2 bond activation have been proposed. We have examined this question in the [FeFe] H2ase I from Clostridium acetobutylicum (CaI) by Fourier-transform infrared (FTIR) spectroscopy with temperature annealing and H/D isotope exchange to identify the relevant redox states and define catalytic transitions. One-electron reduction of Hox led to formation of HredH+ ([4Fe-4S]H2+-FeI-FeI) and Hred' ([4Fe-4S]H1+-FeII-FeI), with both states characterized by low frequency MU-CO IR modes consistent with a fully bridged [2Fe]H. Similar MU-CO IR modes were also identified for HredH+ of the [FeFe] H2ase from Chlamydomonas reinhardtii (CrHydA1). The CaI proton-transfer variant C298S showed enrichment of an H/D isotope-sensitive MU-CO mode, a component of the hydride bound H-cluster IR signal, Hhyd. Equilibrating CaI with increasing amounts of NaDT, and probed at cryogenic temperatures, showed HredH+ was converted to Hhyd. Over an increasing temperature range from 10 to 260 K catalytic turnover led to loss of Hhyd and appearance of Hox, consistent with enzymatic turnover and H2 formation. The results show for CaI that the MU-CO of [2Fe]H remains bridging for all of the "Hred" states and that HredH+ is on pathway to Hhyd and H2 evolution in the catalytic mechanism. These results provide a blueprint for designing small molecule catalytic analogs. PMID- 29792027 TI - Fast and Ultrasensitive Detection of a Nerve Agent Simulant Using Carbazole-Based Nanofibers with Amplified Ratiometric Fluorescence Responses. AB - In this work, we report the fast and ultrasensitive detection of a nerve agent simulant in the gas phase, diethyl chlorophosphate (DCP), by using carbazole based nanofibers from 1. When exposed to trace DCP, the formed pyridine phosphorylated product in 1 nanofibers can cause amplified ratiometric fluorescence responses, i.e., amplified fluorescence quenching via quenching excitons within the diffusion length of 1 nanofibers and simultaneously amplified turn-on fluorescence responses via harvesting excitons within the diffusion length to give the intramolecular charge transfer (ICT) emission at a longer wavelength. On the basis of these amplified ratiometric fluorescence responses, detection of DCP with fast response (ca. 3 s), ultrasensitivity (4 ppb), and improved selectivity is achieved. PMID- 29792028 TI - In Situ Structural Elucidation and Selective Pb2+ Ion Recognition of Polydopamine Film Formed by Controlled Electrochemical Oxidation of Dopamine. AB - Owing to the versatility and biocompatibility, a self-polymerized DA (in the presence of air at pH 8.5 tris buffer solution) as a polydopamine (pDA) film has been used for a variety of applications. Indeed, instability under electrified condition (serious surface-fouling) and structural ambiguity of the pDA have been found to be unresolved problems. Previously, pDA films (has hygroscopic and insoluble property) prepared by various controlled chemical oxidation methods have been examined for the structural analysis using ex situ solid-state NMR and mass spectroscopic techniques. In this work, a new in situ approach has been introduced using an electrochemical quartz crystal microbalance (EQCM) technique for the improved structural elucidation of pDA that has been formed by a controlled electrochemical oxidation of DA on a carboxylic acid functionalized multiwalled carbon nanotube-Nafion (cationic perfluoro polymer) modified electrode (f-MWCNT-Nf) system in pH 7 phosphate buffer solution. Key intermediates like 5,6-dihydroxy indole (DHI; 150.7 g mol-1), dopamine (154.1 g mol-1), Na+, PO42-, and polymeric product of high molecular weight, 2475 g mol-1, have been trapped on f-MWCNT-Nf surface via pi-pi (sp2 carbon of MWCNT and aromatic e-s), covalent (amide-II bonding, minimal), hydrogen, and ionic bonding and identified its molecular weights successfully. The new pDA film system showed well-defined peaks at E degrees ' = 0.25 V and -0.350 vs Ag/AgCl corresponding to the surface-confined dopamine/dopamine quinone and DHI/5,6-indolequinone redox transitions without any surface-fouling complication. As an electroanalytical application of pDA, selective recognition of Pb2+ ion via {(pDA)-hydroquinone Pb0} complexation with detection limit (signal-to-noise ratio = 3) 840 part-per trillion has been demonstrated. PMID- 29792029 TI - Stratification in Drying Films Containing Bidisperse Mixtures of Nanoparticles. AB - Large scale molecular dynamics simulations for bidisperse nanoparticle suspensions with an explicit solvent are used to investigate the effects of evaporation rates and volume fractions on the nanoparticle distribution during drying. Our results show that "small-on-top" stratification can occur when Pe sphi s ? c with c ~ 1, where Pe s is the Peclet number and phi s is the volume fraction of the smaller particles. This threshold of Pe sphi s for "small-on-top" is larger by a factor of ~alpha2 than the prediction of the model treating solvent as an implicit viscous background, where alpha is the size ratio between the large and small particles. Our simulations further show that when the evaporation rate of the solvent is reduced, the "small-on-top" stratification can be enhanced, which is not predicted by existing theories. This unexpected behavior is explained with thermophoresis associated with a positive gradient of solvent density caused by evaporative cooling at the liquid/vapor interface. For ultrafast evaporation the gradient is large and drives the nanoparticles toward the liquid/vapor interface. This phoretic effect is stronger for larger nanoparticles, and consequently the "small-on-top" stratification becomes more distinct when the evaporation rate is slower (but not too slow such that a uniform distribution of nanoparticles in the drying film is produced), as thermophoresis that favors larger particles on the top is mitigated. A similar effect can lead to "large-on-top" stratification for Pe sphi s above the threshold when Pe s is large but phi s is small. Our results reveal the importance of including the solvent explicitly when modeling evaporation-induced particle separation and organization and point to the important role of density gradients brought about by ultrafast evaporation. PMID- 29792031 TI - Composition in the Interface between Clay Mineral Surfaces and Divalent Cation Electrolytes. AB - The interfacial free energy of a solid, which determines its adsorption properties, depends on interactions between the surface and the fluid. A change in surface composition can completely change the behavior of the solid. Decades of work have explored adsorption and its effects at solid-fluid interfaces from the macroscopic perspective and using molecular modeling, so the concept of the electric double layer (EDL) is well established in the community. However, direct, molecular level, experimental observations of the composition within the interface region, and its change with time and conditions, are not abundant. We used cryogenic X-ray photoelectron spectroscopy (cryoXPS) to observe the composition in the clay mineral-solution interface region as a function of bulk solution composition, on illite and chlorite in MgCl2 and CaCl2 electrolytes, over a range of concentrations (1-125 mM), in situ, on vitrified samples. These samples were prepared from very thin smears of centrifuged wet paste that were instantaneously chilled to liquid N2 temperature. They preserved the adsorbed solution in its amorphous state, maintaining the location of the ions and water with respect to the solid, without the disruption that occurs during drying or the rearrangement that results as water crystallizes during freezing. With decreasing ionic strength, we could directly monitor the loss of negative charge in the interface region, producing an anion deficiency, as predicted by theory. The Cl-/Me2+ ratio dropped below 1 for chlorite at 12-25 mM MeCl2 and for illite at 75-100 mM. In addition to better understanding of clay mineral behavior in solution, this work demonstrates that only those clay minerals where surface charge density is the same or lower than that for chlorite contribute to a low salinity enhanced oil recovery response (LS EOR). This explains many of the contradictory results from studies about the role of clay minerals in LS EOR. PMID- 29792030 TI - Role of Counterions in Molecularly Imprinted Polymers for Anionic Species. AB - Small-molecule oxoanions are often imprinted noncovalently as carboxylates into molecularly imprinted polymers (MIPs), requiring the use of an organic counterion. Popular species are either pentamethylpiperidine (PMP) as a protonatable cation or tetraalkylammonium (TXA) ions as permanent cations. The present work explores the influence of the TXA as a function of their alkyl chain length, from methyl to octyl, using UV/vis absorption, fluorescence titrations, and HPLC as well as MD simulations. Protected phenylalanines (Z-l/d-Phe) served as templates/analytes. While the influence of the counterion on the complex stability constants and anion-induced spectral changes shows a monotonous trend with increasing alkyl chain length at the prepolymerization stage, the cross imprinting/rebinding studies showed a unique pattern that suggested the presence of adaptive cavities in the MIP matrix, related to the concept of induced fit of enzyme-substrate interaction. Larger cavities formed in the presence of larger counterions can take up pairs of Z-x-Phe and smaller TXA, eventually escaping spectroscopic detection. Correlation of the experimental data with the MD simulations revealed that counterion mobility, the relative distances between the three partners, and the hydrogen bond lifetimes are more decisive for the response features observed than actual distances between interacting atoms in a complex or the orientation of binding moieties. TBA has been found to yield the highest imprinting factor, also showing a unique dual behavior regarding the interaction with template and fluorescent monomer. Finally, interesting differences between both enantiomers have been observed in both theory and experiment, suggesting true control of enantioselectivity. The contribution concludes with suggestions for translating the findings into actual MIP development. PMID- 29792032 TI - Twisted-Intramolecular-Charge-Transfer-Based Turn-On Fluorogenic Nanoprobe for Real-Time Detection of Serum Albumin in Physiological Conditions. AB - Two cyanine-based fluorescent probes, ( E)-2-(4-(diethylamino)-2-hydroxystyryl)-3 ethyl-1,1-dimethyl-1 H-benzo[ e]indol-3-ium iodide (L) and ( E)-3-ethyl-1,1 dimethyl-2-(4-nitrostyryl)-1 H-benzo[ e]indol-3-ium iodide (L1), have been designed and synthesized. Of these two probes, the twisted-intramolecular-charge transfer (TICT)-based probe, L, can preferentially self-assemble to form nanoaggregates. L displayed a selective turn-on fluorescence response toward human and bovine serum albumin (HSA and BSA) in ~100% aqueous PBS medium, which is noticeable with the naked eye, whereas L1 failed to sense these albumin proteins. The selective turn-on fluorescence response of L toward HSA and BSA can be attributed to the selective binding of probe L with HSA and BSA without its interfering with known drug-binding sites. The specific binding of L with HSA led to the disassembly of the self-assembled nanoaggregates of L, which was corroborated by dynamic-light-scattering (DLS) and transmission-electron microscopy (TEM) analysis. Probe L has a limit of detection as low as ~6.5 nM. The sensing aptitude of probe L to detect HSA in body fluid and an artificial urine sample has been demonstrated. PMID- 29792033 TI - pSBMA-Conjugated Magnetic Nanoparticles for Selective IgG Separation. AB - Two types of zwitterionic polymer-modified magnetic nanoparticles (NPs) are fabricated by conjugating pSBMA onto PEI-precoated NPs via either a one-step method (1S NPs) or two-step method (2S NPs). For both methods, divinyl sulfone is used as the linker molecule. Although 1S NPs were capable of resisting both IgG and BSA, 2S NPs exhibited specificity toward IgG adsorption in complex biological fluids, e.g., in a mixture of serums and IgG. The moderate interactions ( Kd ~ 1.2 MUM) between IgG and 2S NPs are 3 orders of magnitude lower than IgG binding with protein A ( Kd 10 nM). Through complementary characterizations and analyses, we rationalize that the surface developed herein with IgG specificity contains two key components: polyzwitterions with a short chain length and sulfone groups with a high density. PMID- 29792024 TI - Metabotropic Glutamate Receptors in Alcohol Use Disorder: Physiology, Plasticity, and Promising Pharmacotherapies. AB - Developing efficacious treatments for alcohol use disorder (AUD) has proven difficult. The insidious nature of the disease necessitates a deep understanding of its underlying biology as well as innovative approaches to ameliorate ethanol related pathophysiology. Excessive ethanol seeking and relapse are generated by long-term changes to membrane properties, synaptic physiology, and plasticity throughout the limbic system and associated brain structures. Each of these factors can be modulated by metabotropic glutamate (mGlu) receptors, a diverse set of G protein-coupled receptors highly expressed throughout the central nervous system. Here, we discuss how different components of the mGlu receptor family modulate neurotransmission in the limbic system and other brain regions involved in AUD etiology. We then describe how these processes are dysregulated following ethanol exposure and speculate about how mGlu receptor modulation might restore such pathophysiological changes. To that end, we detail the current understanding of the behavioral pharmacology of mGlu receptor-directed drug-like molecules in animal models of AUD. Together, this review highlights the prominent position of the mGlu receptor system in the pathophysiology of AUD and provides encouragement that several classes of mGlu receptor modulators may be translated as viable treatment options. PMID- 29792034 TI - Soft Hydrogel Zwitterionic Coatings Minimize Fibroblast and Macrophage Adhesion on Polyimide Substrates. AB - Minimizing the foreign body reaction to polyimide-based implanted devices plays a pivotal role in several biomedical applications. In this work, we propose materials exhibiting nonbiofouling properties and a Young's modulus reflecting that of soft human tissues. We describe the synthesis, characterization, and in vitro validation of poly(carboxybetaine) hydrogel coatings covalently attached to polyimide substrates via a photolabile 4-azidophenyl group, incorporated in poly(carboxybetaine) chains at two concentrations of 1.6 and 3.1 mol %. The presence of coatings was confirmed by attenuated total reflectance Fourier transform infrared spectroscopy. White light interferometry was used to evaluate the coating continuity and thickness (between 3 and 6 MUm under dry conditions). Confocal laser scanning microscopy allowed us to quantify the thickness of the swollen hydrogel coatings that ranged between 13 and 32 MUm. The different hydrogel formulations resulted in stiffness values ranging from 2 to 19 kPa and led to different fibroblast and macrophage responses in vitro. Both cell types showed a minimum adhesion on the softest hydrogel type. In addition, both the overall macrophage activation and cytotoxicity were observed to be negligible for all of the tested material formulations. These results are a promising starting point toward future advanced implantable systems. In particular, such technology paves the way for novel neural interfaces able to minimize the fibrotic reaction, once implanted in vivo, and to maximize their long-term stability and functionality. PMID- 29792035 TI - 3-Substituted 1,5-Diaryl-1 H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 2: Selection and Evaluation of [11C]PS13 for Quantitative Imaging. AB - In our preceding paper (Part 1), we identified three 1,5-bis-diaryl-1,2,4 triazole-based compounds that merited evaluation as potential positron emission tomography (PET) radioligands for selectively imaging cyclooxygenase-1 (COX-1) in monkey and human brain, namely, 1,5-bis(4-methoxyphenyl)-3-(alkoxy)-1 H-1,2,4 triazoles bearing a 3-methoxy (PS1), a 3-(2,2,2-trifluoroethoxy) (PS13), or a 3 fluoromethoxy substituent (PS2). PS1 and PS13 were labeled from phenol precursors by O-11C-methylation with [11C]iodomethane and PS2 by O-18F-fluoroalkylation with [2H2,18F]fluorobromomethane. Here, we evaluated these PET radioligands in monkey. All three radioligands gave moderately high uptake in brain, although [2H2,18F]PS2 also showed undesirable radioactivity uptake in skull. [11C]PS13 was selected for further evaluation, mainly based on more favorable brain kinetics than [11C]PS1. Pharmacological preblock experiments showed that about 55% of the radioactivity uptake in brain was specifically bound to COX-1. An index of enzyme density, VT, was well identified from serial brain scans and from the concentrations of parent radioligand in arterial plasma. In addition, VT values were stable within 80 min, suggesting that brain uptake was not contaminated by radiometabolites. [11C]PS13 successfully images and quantifies COX-1 in monkey brain, and merits further investigation for imaging COX-1 in monkey models of neuroinflammation and in healthy human subjects. PMID- 29792036 TI - Meeting the challenge for effective antimicrobial stewardship programs in regional, rural and remote hospitals - what can we learn from the published literature? AB - INTRODUCTION: Antimicrobial resistance (AMR) has been recognised as an urgent health priority, both nationally and internationally. Australian hospitals are required to have an antimicrobial stewardship (AMS) program, yet the necessary resources may not be available in regional, rural or remote hospitals. This review will describe models for AMS programs that have been introduced in regional, rural or remote hospitals internationally and showcase achievements and key considerations that may guide Australian hospitals in establishing or sustaining AMS programs in the regional, rural or remote hospital setting. METHODS: A narrative review was undertaken based on literature retrieved from searches in Ovid Medline, Scopus, Web of Science and the grey literature. 'Cited' and 'cited by' searches were undertaken to identify additional articles. Articles were included if they described an AMS program in the regional, rural or remote hospital setting (defined as a bed size less than 300 and located in a non metropolitan setting). RESULTS: Eighteen articles were selected for inclusion. The AMS initiatives described were categorised into models designed to address two different challenges relating to AMS program delivery in regional, rural and remote hospitals. This included models to enable regional, rural and remote hospital staff to manage AMS programs in the absence of on-site infectious diseases (ID) trained experts. Non-ID doctor-led, pharmacist-led and externally led initiatives were identified. Lack of pharmacist resources was recognised as a core barrier to the further development of a pharmacist-led model. The second challenge was access to timely off-site expert ID clinical advice when required. Examples where this had been overcome included models utilising visiting ID specialists, telehealth and hospital network structures. Formalisation of such arrangements is important to clarify the accountabilities of all parties and enhance the quality of the service. Information technology was identified as a facilitator to a number of these models. The variance in availability of information technology between hospitals and cost limits the adoption of uniform programs to support AMS. CONCLUSION: Despite known barriers, regional, rural and remote hospitals have implemented AMS programs. The examples highlighted show that difficulty recruiting ID specialists should not inhibit AMS programs in regional, rural and remote hospitals, as much of the day-to-day work of AMS can be done by non-experts. Capacity building and the strengthening of networks are core features of these programs. Descriptions of how Australian regional, rural and remote hospitals have structured and supported their AMS programs would add to the existing body of knowledge sourced from international examples. Research into AMS programs predominantly led by GPs and nursing staff will provide further possible models for regional, rural and remote hospitals. PMID- 29792037 TI - The effect of iodopovidone versus bleomycin in chemical pleurodesis. AB - Background Malignant pleural effusion continues to be a common problem in patients with metastatic disease. This study was conducted to compare the efficacy and safety of bleomycin pleurodesis with povidone-iodine pleurodesis through a chest drain as palliative treatment for recurrent malignant pleural effusion. Methods Sixty cancer patients (36 males and 24 females) with recurrent malignant pleural effusion were enrolled in a prospective randomized trial. Thirty patients received povidone-iodine pleurodesis and 30 received bleomycin pleurodesis. Age, sex, side of the primary pathology, treatment outcome (recurrence and relapse time), and complications were analyzed. Results The mean age was 59.63 +/- 7.68 years in the povidone-iodine group and 57.97 +/- 9.27 years in the bleomycin group ( p = 0.452). The complications were identical in both groups: 2 (6.7%) patients had chest pain, 2 (6.7%) had fever, and one (3.3%) had hypotension. There was a good response to therapy in 20 (66.7%) patients in the bleomycin group and 25 (83.3%) in the povidone-iodine group ( p = 0.136). Conclusion The results of this study indicate that povidone-iodine should be considered as a selective chemical agent to perform pleurodesis in patients with recurrent malignant pleural effusion because it has the same effect but costs less than bleomycin. PMID- 29792039 TI - Identifying Palliative Care Needs Among Older Adults in Nonclinical Settings. AB - Though palliative care is appropriate for patients with serious illness at any stage of the illness and treatment process, the vast majority of palliative care is currently delivered in inpatient medical settings in the past month of life during an acute hospitalization. Palliative care can have maximal benefit to patients when it is integrated earlier in the illness trajectory. One possible way to increase earlier palliative care use is to screen for unmet palliative care needs in community settings. The goal of this study was to assess the rates of unmet palliative care needs in older adults who attend New York City-based senior centers. The results of this study revealed that 28.8% of participants screened positive for unmet palliative care needs. Lower education and living alone were predictors of positive palliative care screens, but age, gender, marital status, and race were not. This study determined that the rate of unmet palliative care needs in community-based older adults who attend senior center events was high and that living arrangement and education level are both correlates of unmet palliative care needs. Screening for unmet palliative care needs in community settings is a promising approach for moving palliative care upstream to patients who could benefit from the additional supportive services prior to an acute hospitalization. PMID- 29792038 TI - Downregulation of Cancer Stemness by Novel Diterpenoid Ovatodiolide Inhibits Hepatic Cancer Stem Cell-Like Traits by Repressing Wnt/[Formula: see text] Catenin Signaling. AB - The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities. Our fluorescence-activated cell sorting (FACS) and quantitative RT-PCR analyses of side population (SP) indicated that CD133+ cells were [Formula: see text]-catenin-overexpressing, more aggressive, and resistant to the conventional anticancer agents, Cisplatin and Doxorubicin, when compared to [Formula: see text]-catenin-downregulated group. We demonstrated that marked upregulation of [Formula: see text]-catenin and its downstream targets effectively enhanced hepatosphere formation, with an associated induction of CD133, OCT4 and Sox2 expression and also caused an significant enhancement of HCC proliferation. However, treatment with Ovatodiolide induced downregulation of [Formula: see text]-catenin and its downstream effector genes, abolished hepatosphere formation and reversed the [Formula: see text]-catenin-associated enhancement of HCC growth. In summary, we demonstrated for the first time that Ovatodiolide suppressed the canonical Wnt signaling pathway, and inhibited the generation of liver CSCs; Thus, projecting Ovatodiolide as a putatively effective therapeutic agent for anti-HCC target therapy. PMID- 29792040 TI - Lung cancer screening with MRI: characterization of nodules with different non enhanced MRI sequences. AB - Background There is increased interest in pulmonary magnetic resonance imaging (MRI) as a radiation-free alternative to computed tomography (CT) for lung cancer screening. Purpose To analyze MRI characteristics of pulmonary nodules with different non-enhanced sequences. Material and Methods Eighty-two participants of a lung cancer screening were included. MRI datasets of 32 individuals with 46 different nodules >= 6 mm were prospectively evaluated together with 50 controls by two readers. Acquired sequences were T2- short tau inversion recovery (STIR), T2, balanced steady-state free precession (bSSFP), 3D-T1, and diffusion-weighted imaging (DWI). Each sequence was randomly and separately viewed blinded to low dose CT (LDCT). Size, shape, and contrast of nodules were evaluated on each sequence and then correlated with LDCT and histopathology. Results All eight carcinomas were detected by T2-STIR, T2, and bSSFP, and 7/8 by 3D-T1. Contrast was significantly higher for malignant nodules on all sequences. The highest contrast ratio between malignant and benign nodules was provided by T2-STIR. Of eight carcinomas, seven showed restricted diffusion. Size measurement correlated significantly between MRI and LDCT. Sensitivity/specificity for nodules >= 6 mm was 85-89%/92-94% for T2-STIR, 80-87%/93-96% for T2, 65-70%/96-98% for bSSFP, and 63-67%/96-100% for 3D-T1. Seven of eight subsolid nodules were visible on T2 sequences with significantly lower lesion contrast compared to solid nodules. Two of eight subsolid nodules were detected by bSFFP, none by 3D-T1. All three calcified nodules were detected by 3D-T1, one by bSSFP, and none by T2-sequences. Conclusion Malignant as well as calcified and subsolid nodules seem to have distinctive characteristics on different MRI sequences. T2-imaging was most suitable for the detection of nodules >= 6 mm. PMID- 29792041 TI - Increased diagnostic confidence in the diagnosis of pituitary micro-lesions with the addition of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions sequences. AB - Background Conventional magnetic resonance imaging (MRI) is adversely affected by thick slices, small intersection gaps, and the partial volume effect, leading to the missed diagnosis or misdiagnosis of pituitary micro-lesions. Purpose To evaluate the diagnostic yield of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-T2 SPACE) sequences compared with a standard MRI protocol for the diagnosis of pituitary micro-lesions. Material and Methods The MRI findings of 664 patients with clinically suspected pituitary lesions were retrospectively analyzed. All patients underwent coronal 3D-T2 SPACE sequences followed by T1-weighted (T1W) imaging. Conventional scanning sequences included coronal and sagittal T1W imaging and post-contrast enhanced coronal and sagittal T1 imaging. All images were independently evaluated by two experienced neuroradiologists. The inter observer agreement was analyzed using kappa statistics. Results Compared with conventional sequences, there was an increase in diagnostic confidence of 60.3% for the diagnosis of pituitary micro-lesions with the addition of 3D-T2 SPACE sequences. The lesion conspicuity scores of combined conventional and 3D-T2 SPACE sequences were significantly higher than those of conventional imaging (z = 6.403, P < 0.01) and 3D-T2 SPACE sequences (z = -4.243, P < 0.01). In addition, the inter-observer agreement of 3D-T2 SPACE sequences was good (kappa = 0.826). Conclusion Combined with routine sequences, post-contrast enhanced 3D-T2 SPACE sequences effectively improve diagnostic confidence in the diagnosis of pituitary micro-lesions. Post-contrast enhanced 3D-T2 SPACE is suitable for detecting pico adenomas, micro-lesions adjacent to the cavernous sinuses or sellar floor, lesions between the anterior and posterior lobes, and lesions with early phase enhancement. PMID- 29792042 TI - Imaging predictors of outcome in acute spontaneous subarachnoid hemorrhage: a review of the literature. AB - Spontaneous subarachnoid hemorrhage (SAH) accounts for about 5% of strokes, but has a very high morbidity and mortality. Many survivors are left with important cognitive impairment and are severely incapacitated. Prediction of complications such as vasospasm and delayed cerebral ischemia, and of clinical outcome after SAH, is challenging. Imaging studies are essential in the initial evaluation of SAH patients and are increasingly relevant in assessing for complications and prognosis. In this article, we reviewed the role of imaging studies in evaluating early brain injury and predicting complications as well as clinical and neuropsychological prognosis after acute SAH. PMID- 29792043 TI - Does the mass of sample loaded affect faecal haemoglobin concentration using the faecal immunochemical test? AB - Background Quantitative faecal immunochemical tests (FIT) for haemoglobin are being used for colorectal cancer (CRC) screening for asymptomatic populations and are being indicated as a suitable test to rule out CRC in symptomatic populations. Faecal samples are typically collected by patients using a probe attached to the cap of a device which is inserted into a collection device into the preservative buffer, passing through a collar to remove excess sample: this process has potential for pre-analytical error. This study investigates whether faecal haemoglobin concentration (f-Hb) results are affected by the mass and method of sample collection. Methods Faecal samples with detectable f-Hb were loaded into collection devices from four manufacturers using increasing masses of sample. The f-Hb in the device buffer was measured using the relevant analyser. The results from the minimum recommended load were compared with results of 'sample overloading'. Results The variation in the faecal mass added to the probe (overall CVs: EXTEL HEMO AUTO-MC Collection Picker 300%, OC-Auto Sampling Bottle 3 237%, SENTiFIT pierceTube 264%, Specimen Collection Container A 250%), was more than the variation in f-Hb (respective overall CVs: 62%, 35%, 47%, 39%). The mass of faeces added to the probes increased significantly ( P < 0.0001 for all four devices), but the f-Hb did not increase significantly (EXTEL HEMO AUTO-MC Collection Picker P = 0.6820, OC-Auto Sampling Bottle 3 P = 0.9368, SENTiFIT pierceTube P = 0.7551, Specimen Collection Container A P = 0.6864). Conclusion The mass of sample loaded onto the probe did not impact the f-Hb significantly using all four tested devices. PMID- 29792044 TI - An assessment of the effect of haemoglobin variants on detection by faecal immunochemical tests. AB - Background Faecal immunochemical tests (FIT) for haemoglobin (Hb) are being used in the investigation of colorectal cancer. These tests use antibodies raised to the globin moiety of human Hb. Where the globin structure is abnormal or reduced, it is possible that antibody binding, and thus Hb-detection may be affected. Methods Lysates prepared from whole blood samples of patients with known variants were diluted in manufacturer-specific buffer to 10, 100 and 500 MUg Hb/g faeces. These samples were analysed on four FIT analysers and the results compared with samples with no known variant present (normal samples). Results The results from this study show that of 20 variants tested, three showed a decrease in detection by all four analysers. These were beta-thalassaemia major and two fetal cord blood samples. Conclusions Of 20 common Hb variants studied, 17 did not affect detection of Hb by the FIT systems tested. Hb variants leading to a reduction in the presence of a globin chain caused a reduction in Hb detection; in such cases, cancers could be missed. PMID- 29792045 TI - Renal stones. AB - Renal stone disease is a worldwide problem which carries significant morbidity. It frequently requires specialist urology intervention. Patients with recurrent disease and those at high risk require specialist investigations and review. Certain cases benefit from medical and surgical intervention. In this review, we discuss the pathophysiology, risk assessment, specialist investigations and various interventions, their rationale and evidence base. This review aims to provide an update of the previous publication in 2001 in this journal on this topic. PMID- 29792046 TI - Fast screening of N-glycosylation disorders by sialotransferrin profiling with capillary zone electrophoresis. AB - Background Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most frequently used screening method is sialotransferrin profiling using isoelectric focusing (IEF). Capillary zone electrophoresis (CZE) may be a simple and fast alternative. We investigated the CapillarysTM CDT assay (Sebia, France) to screen for N-glycosylation disorders, using IEF as gold standard. Methods Intra- and inter-assay precision were established, and analyses in heparin-anticoagulated plasma and serum were compared. Accuracy was assessed by comparing IEF and CZE profiles of 153 samples, including 49 normal, 53 CDG type I, 2 CDG type II, 1 combined CDG type I and type II and 48 samples with a Tf-polymorphism. Neuraminidase-treated plasma was analysed to discriminate CDG and Tf-polymorphisms using samples of 52 subjects (25 had a confirmed Tf-polymorphism). Age-dependent reference values were established using profiles of 312 samples. Results Heparin-plasma is as suitable as serum for CDG screening with the CapillarysTM CDT assay. The precision of the method is high, with a limit of quantification (LOQ) of 0.5%. All profiles, including CDG and Tf-polymorphisms, were correctly identified with CZE. Forty nine of 52 neuraminidase-treated samples correctly identified the presence/absence of a Tf-polymorphism. Interferences in 3/52 samples hampered interpretation. Sialo-Tf profiles were dependent of age, in particular in the first three months of age. Conclusions CZE analysis with the CapillarysTM CDT kit (Sebia) is a fast and reliable method for screening of N-glycosylation defects. Tf-polymorphisms could be excluded after overnight incubation with neuraminidase. PMID- 29792047 TI - Phenotyping and relative quantification of vitamin D binding protein in a paediatric population by using liquid chromatography-tandem mass spectrometry. AB - Background Adequate concentrations of vitamin D are required to ensure bone health and minimize the incidence of multiple extraskeletal diseases. Although total 25-hydroxyvitamin D (25OHD) remains the recommended biomarker for assessing vitamin D status, it has been speculated that free 25OHD correlates better with clinical outcomes. The calculation of free 25OHD depends on the concentrations of vitamin D binding protein (DBP), the determination of which involves different immunoassays and has led to varying results and conclusions. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous identification and relative quantification of DBP isoforms. Methods We used serum samples from healthy children ( n = 79), mainly Caucasian (88%). Proteins were denatured, reduced, alkylated and digested with trypsin. Purified peptides were analysed by LC-MS/MS. The DBP phenotype was established by using the combinations of tryptic peptides associated with each of the three isoforms and one peptide common to all of them to perform relative quantification. The genotyping of volunteers ( n = 7) facilitated verification of the ability of our method to correctly identify the DBP phenotype. Results The DBP phenotype was correctly established in all samples from volunteers, based on the 100% correlation observed with the genotype. The most common DBP phenotype in Caucasian children was 2/1S (34%) and the rarest 1F/1F (2%). The relative quantification of DBP concentrations did not show statistically significant differences between phenotypes ( P = 0.11). Conclusions LC-MS/MS enabled simultaneous phenotyping and relative quantification of DBP, while avoiding the analytical limitations of immunoassays and confirming similar concentrations of DBP in all phenotypes. PMID- 29792049 TI - Five-Year Suicidal Ideation Trajectories Among Women Receiving or Being Denied an Abortion. AB - OBJECTIVE: The aim of this study was to assess the effects of receiving compared with being denied an abortion on women's experiences of suicidal ideation over 5 years. METHOD: The authors recruited 956 women from 30 U.S. abortion facilities. Women were interviewed by telephone 1 week after their abortion visit, then every 6 months for 5 years. Women who received near-limit abortions were compared with women who were denied an abortion and carried their pregnancies to term (turnaway birth group). Women completed the suicidal ideation items on the Brief Symptom Interview (BSI) and the Patient Health Questionnaire (PHQ-9). The Sheehan Suicidality Tracking Scale was used to assess imminent suicidality. Adjusted mixed-effects regression analyses accounting for clustering by site and individual were used to assess whether levels and trajectories of suicidality differed by group. RESULTS: One week after abortion seeking, 1.9% of the near limit group and 1.3% of the turnaway-birth group reported any suicidal ideation symptoms on the BSI. Over the 5-year study period, the proportion of women with any suicidal ideation symptoms on the BSI declined significantly to 0.25% for women in the near-limit group and nonsignificantly to 0.21% for those in the turnaway-birth group. In four out of 7,247 observations (0.06%), women reported being imminently suicidal. There was no statistically significant differential loss to follow-up by baseline report of suicidal ideation or history of depression or anxiety. There were no statistically significant group differences on any suicidal ideation outcome over the 5-year study period. CONCLUSIONS: Levels of suicidal ideation were similarly low between women who had abortions and women who were denied abortions. Policies requiring that women be warned that they are at increased risk of becoming suicidal if they choose abortion are not evidence based. PMID- 29792048 TI - A novel high-throughput assay for the measurement of salivary progesterone by liquid chromatography tandem mass spectrometry. AB - Background Liquid chromatography tandem mass spectrometry (LC-MS/MS) enables specific and sensitive quantification of steroids with a high throughput. Saliva sampling is advantageous for multisample profiling over longer periods of time, as it is non-invasive, cheap, can be carried out at home and does not require the attendance of clinical personnel. We developed a rapid LC-MS/MS for the measurement of salivary progesterone, frequently assessed as ovulation marker in patients desiring fertility. Methods Samples (300 MUL) were prepared by supported liquid extraction using dichloromethane and were reconstituted in 40% methanol. Chromatography was performed using a C8 column with a water/methanol gradient containing 0.1% formic acid and 2 mmol/L ammonium acetate. Quantification was performed with a Waters TQ-S mass spectrometer. Results Total run time was 5.5 min. The lower limit of quantification was 20 pmol/L (1.2 fmol on column). Inter- and intra-assay comparison showed coefficients of variation and bias between measured and nominal concentrations of less than 11%. Mean recovery was 91%. Interference with a large set of natural and synthetic steroids was excluded. The assay was successfully applied to measure progesterone variation during the menstrual cycle ( n = 9) and diurnal variations during luteal phase ( n = 7) in regularly cycling women. Discussion We present a novel LC-MS/MS assay for the determination of salivary progesterone with high-throughput potential. The applicability of the assay for progesterone profiling during the menstrual cycle is demonstrated. PMID- 29792050 TI - Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The authors conducted a systematic review and meta-analysis to determine whether the risk of psychosis is higher in past or future episodes in patients with major depression with psychotic features than in patients with nonpsychotic depression. METHOD: PubMed, Embase, and PsycINFO were searched, and studies were selected that 1) identified patients with unipolar major depression, 2) made diagnoses of psychosis based on the presence of delusions or hallucinations, 3) characterized past or subsequent episodes as psychotic or nonpsychotic, and 4) were published in English. Two meta-analyses were then conducted using data from patients having index depressive episodes with or without psychosis at study entry to determine the risk of any prior or subsequent psychotic episode and the risk of psychosis in all episodes. RESULTS: Twelve studies met the inclusion criteria, and altogether they included 546 psychotic and 1,583 nonpsychotic patients with unipolar depression. In seven of the studies, the risk ratio for a prior or subsequent psychotic episode in patients whose index depressive episode was psychotic compared with those whose index episode was nonpsychotic was 9.98 (95% CI=4.75, 20.94). In eight studies, the risk ratio for psychosis among all episodes of depression in the subgroups with psychotic and nonpsychotic index episodes was 7.24 (95% CI=5.03, 10.43). Differences in risk of psychosis between these subgroups remained robust when potential sources of heterogeneity were explored. CONCLUSIONS: The findings support the hypothesis that psychotic depression runs true to form, and they support the distinction between psychotic and nonpsychotic depression. Because patients with psychotic depression are at high risk for psychosis in future episodes, determination of effective preventive treatments is imperative. PMID- 29792051 TI - Predicting Suicide Attempts and Suicide Deaths Following Outpatient Visits Using Electronic Health Records. AB - OBJECTIVE:: The authors sought to develop and validate models using electronic health records to predict suicide attempt and suicide death following an outpatient visit. METHOD:: Across seven health systems, 2,960,929 patients age 13 or older (mean age, 46 years; 62% female) made 10,275,853 specialty mental health visits and 9,685,206 primary care visits with mental health diagnoses between Jan. 1, 2009, and June 30, 2015. Health system records and state death certificate data identified suicide attempts (N=24,133) and suicide deaths (N=1,240) over 90 days following each visit. Potential predictors included 313 demographic and clinical characteristics extracted from records for up to 5 years before each visit: prior suicide attempts, mental health and substance use diagnoses, medical diagnoses, psychiatric medications dispensed, inpatient or emergency department care, and routinely administered depression questionnaires. Logistic regression models predicting suicide attempt and death were developed using penalized LASSO (least absolute shrinkage and selection operator) variable selection in a random sample of 65% of the visits and validated in the remaining 35%. RESULTS:: Mental health specialty visits with risk scores in the top 5% accounted for 43% of subsequent suicide attempts and 48% of suicide deaths. Of patients scoring in the top 5%, 5.4% attempted suicide and 0.26% died by suicide within 90 days. C-statistics (equivalent to area under the curve) for prediction of suicide attempt and suicide death were 0.851 (95% CI=0.848, 0.853) and 0.861 (95% CI=0.848, 0.875), respectively. Primary care visits with scores in the top 5% accounted for 48% of subsequent suicide attempts and 43% of suicide deaths. C statistics for prediction of suicide attempt and suicide death were 0.853 (95% CI=0.849, 0.857) and 0.833 (95% CI=0.813, 0.853), respectively. CONCLUSIONS:: Prediction models incorporating both health record data and responses to self report questionnaires substantially outperform existing suicide risk prediction tools. PMID- 29792052 TI - Randomized Clinical Trial of Computerized and Clinician-Delivered CBT in Comparison With Standard Outpatient Treatment for Substance Use Disorders: Primary Within-Treatment and Follow-Up Outcomes. AB - OBJECTIVE: Previous trials have demonstrated the efficacy and durability of computer-based cognitive-behavioral therapy (CBT4CBT) as an add-on to standard outpatient care in a range of treatment-seeking populations. In this study, the authors evaluated the efficacy and safety of CBT4CBT as a virtual stand-alone treatment, delivered with minimal clinical monitoring, and clinician-delivered cognitive-behavioral therapy (CBT) compared with treatment as usual in a heterogeneous sample of treatment-seeking outpatients with substance use disorders. METHOD: This was a randomized clinical trial in which 137 individuals who met DSM-IV-TR criteria for current substance abuse or dependence were randomly assigned to receive treatment as usual, weekly individual CBT, or CBT4CBT with brief weekly monitoring. RESULTS: Rates of treatment exposure differed by group, with the best retention in the CBT4CBT group and the poorest in the individual CBT group. Participants who received CBT or CBT4CBT reduced their frequency of substance use significantly more than those who received treatment as usual. Six-month follow-up outcomes indicated continuing benefit of CBT4CBT (plus monitoring) over treatment as usual, but not for clinician delivered CBT over treatment as usual. Analysis of secondary outcomes indicated that participants in the CBT4CBT group demonstrated the best learning of cognitive and behavioral concepts, as well as the highest satisfaction with treatment. CONCLUSIONS: This first trial of computerized CBT as a virtual stand alone intervention delivered in a clinical setting to a diverse sample of patients with current substance use disorders indicated that it was safe, effective, and durable relative to standard treatment approaches and was well liked by participants. Clinician-delivered individual CBT, while efficacious within the treatment period, was unexpectedly associated with a higher dropout rate and lower effects at follow-up. PMID- 29792053 TI - Proceedings of the 2018 Spring Meeting of the Society of British Neurological Surgeons. PMID- 29792054 TI - Corrigendum. PMID- 29792055 TI - The effect of the modes of delivery on the maternal and neonatal dynamic thiol disulfide homeostasis. AB - BACKGROUND: Thiols are organic compounds containing sulfhydryl groups which exert antioxidant effects via dynamic thiol-disulfide homeostasis. The shift towards disulfide indicates the presence of oxidative environment. The thiol-disulfide homeostasis has not been studied in different mode of delivery before. AIMS: To investigate the effects of mode of parturition on the thiol-disulfide homeostasis in mothers and term infants. STUDY DESIGN: The participants were grouped according to the mode of their delivery: group vaginal delivery (VD, n = 40) and group cesarean section (C/S, n = 40). Three serum samples were collected: from mothers at the beginning of labor, from the cord blood (CB), and from the infants at the 24th hour after birth. The dynamic thiol-disulfide homeostasis in both groups were compared. RESULTS: The levels of native-thiol and total-thiol in CB were significantly higher in VD group than those with C/S group. The levels of disulfide were higher in infants born by C/S compared with those born by VD. The disulfide-to-native thiol ratio, disulfide-to-total thiol ratio, and native thiol to-total thiol ratio were similar between two groups. CONCLUSION: Our results showed that the dynamic thiol-disulfide homeostasis of the neonate was greatly influenced by the way of delivery and supported that vaginally delivered infants have less oxidative stress. PMID- 29792056 TI - Placenta in intrauterine fetal demise (IUFD): a comprehensive study from a tertiary care hospital. AB - BACKGROUND: Intrauterine fetal demise (IUFD) is an unpredictable and challenging obstetric complication. Its etiology is multifactorial with more than 60% attributed to the placental cause. The present study was done with a primary objective of understanding the placental lesions underlying IUFD. METHODS: In this retrospective observational study, IUFD cases (>22 weeks) between January 2012 and September 2015 were collected from pathology database. The clinical details with ultrasound findings were collected from mother's charts. The lesions were classified into (A) maternal vascular malperfusion (MVM) including retroplacental hematomas, (B) fetal vascular malperfusion (FVM), (C) inflammatory lesions, and (D) idiopathic. The contributor to fetal death was classified as direct, major, minor, unlikely, or unknown. Placental findings of fetal hypoxia were recorded. RESULTS: The study included 100 cases of IUFD. The mean maternal age was 26 years (18-36 years). Primipara were 46. There were 65 early preterm (PT) (<34 weeks), 20 late PT (34 weeks to <37 weeks) and 15 term (>37 weeks) IUFD. The mean gestation age was 30 weeks. The ratio of male:female fetuses was 1:1.7. Relevant obstetric complications included preeclampsia (n = 39), intrauterine growth restriction (IUGR) (n = 7), pre-gestational diabetes (n = 7), bad obstetric history (n = 6), oligohydramnios (n = 5). The mean placental weight was 256 g. Maternal vascular malperfusion had the highest incidence (30%), followed by combined maternal and FVM (10%). Exclusive inflammatory lesions and FVM were seen in 12 and 6%, respectively. No cause was identified in 18%. Direct contributor to IUFD was identified in 51 cases and major, minor, unlikely contribution in 21, 11 and nine cases, respectively. In nine cases, it was unknown. Lesions indicating fetal hypoxia were noted in 35 cases. In both early and late PT, MVM featured more commonly (23 and 5%). In term placentas, the most common cause was idiopathic. CONCLUSIONS: Lesions of MVM were the most common cause of IUFD and served as a direct contributor to fetal demise. PMID- 29792057 TI - Optimizing Pyxis to Reduce the Cost of Hyperinflation Medications. PMID- 29792058 TI - Utilization of progesterone and cervical length screening for prevention of recurrent preterm birth. AB - OBJECTIVE: To assess utilization of progesterone and cervical length (CL) screening among women with prior spontaneous preterm birth (sPTB). METHODS: This is a retrospective cohort study of women with prior sPTB. Primary outcomes were the use of progesterone and CL screening. Secondary outcomes were reasons for failure to utilize interventions and factors associated with use of recommended interventions. RESULTS: 180 women had a prior sPTB. Of 171 women eligible for progesterone, 125 (74%) utilized it. Women who utilized progesterone were more likely to have a prior sPTB <28 weeks (50% vs 26%, OR 2.54 (1.18-5.42) p = .006) and a higher number of prior sPTB (1.5 +/- 0.9 vs 1.2 +/- 0.5, p = .02), and less likely to have a prior full term delivery (54% vs 72%, OR 0.47 (0.22-0.99), p = .04). Of 176 women eligible for CL screening, 157 (89%) utilized it. Women who utilized CL screening were less likely to have a prior full term delivery (59% vs 84%, OR 0.27 (0.07-0.95, p = .01)). The most frequent reason for lack of progesterone and CL screening was patient declining. CONCLUSION: Most women with prior sPTB received progesterone and CL screening. Those at highest risk for PTB based on obstetric history are more likely to utilize recommended interventions. PMID- 29792059 TI - Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture. AB - Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture (LP) remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, LP is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematologic tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo LP. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with LP. PMID- 29792060 TI - Warfarin monitoring with viscoelastic haemostatic assays, thrombin generation, coagulation factors and correlations to Owren and Quick prothrombin time. AB - The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66 0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis. PMID- 29792061 TI - Diet and exercise for preeclampsia prevention in overweight and obese pregnant women: systematic review and meta-analysis. AB - OBJECTIVE: To investigate the effect of diet and/or exercise in overweight or obese pregnant women on the risk of preeclampsia (PE). METHODS: We performed a systematic review and meta-analysis of randomized controlled trials examining the effect of diet and/or exercise interventions in overweight and obese pregnant women on the risk of PE and hypertensive disorders. We completed a literature search through PubMed, Embase, Cinahl, Web of science, Cochrane CENTRAL Library from their earliest entries to November 2017 and from references of other systematic reviews. No language restrictions were applied. Relative risks (RR) with random effect were calculated with their 95% confidence intervals (CI). RESULTS: There were 23 eligible trials (7236 participants), including 11 (5023 participants) investigating the effect of diet and three (387 participants) investigating the effect of exercise on risk of PE, 14 (4345 participants) investigating the effect of diet, five (884 participants) investigating the effect of exercise and one (304 participants) investigating the effect of diet and exercise on risk of hypertensive disorders. Most studies were considered to be at low risk of bias for random sequence allocation and incomplete outcome data but at high risk of bias for blinding of participant and personnel. The heterogeneity of the studies on PE was low (I2 = 0-11%), but the heterogeneity of the studies on hypertensive disorders was variable (I2 = 0-53%). In women randomized to diet and/or exercise, compared to expectant management, there was no significant difference in the risk of PE (RR 1.01, 95% CI 0.80-1.27; p = .96) or hypertensive disorders of pregnancy (RR 0.87, 95% CI 0.70-1.06; p = .17). In the intervention group, compared to expectant management, gestational weight gain was significantly lower (-1.47 kg, 95% CI -1.97 to -0.97; p < .00001). Metaregression weighted by the size of the studies showed no significant association between gestational weight gain and the risk of PE or hypertensive disorders (p = .314 and p = .124, respectively). CONCLUSIONS: Diet and exercise in overweight or obese pregnant women are beneficial in reducing gestational weight gain. However, these interventions do not reduce the risk of PE or hypertensive disorders of pregnancy. PMID- 29792062 TI - Analysis of the Blood Viscosity Behavior in the Sicilian Study on Juvenile Myocardial Infarction. AB - Considering the role of hemorheology in coronary circulation, we studied blood viscosity in patients with juvenile myocardial infarction. We examined whole blood viscosity at high shear rate using the cone-on-plate viscosimeter Wells Brookfield 1/2 LVT and at low shear rate employing a viscometer Contraves LS30 in 120 patients (aged <46 years) with myocardial infarction, at the initial stage and subsequently 3 and 12 months after. At the initial stage, patients had an increased whole blood viscosity in comparison to normal controls. This hemorheological profile was not influenced by the cardiovascular risk factors, nor by the extent of coronary lesions, even if some differences were evident between patients with ST-segment elevation myocardial infarction (STEMI) and non STEMI (NSTEMI). The blood viscosity pattern at the initial stage did not influence recurring ischemic events or the onset of heart failure during an 18 months' follow-up. The neutrophil to lymphocyte ratio did not affect the blood viscosity pattern. We reevaluated 83 patients 3 months after and 70 patients 12 months after the acute coronary syndrome, and we found that the hemorheological parameters were still altered in comparison to normal controls at both times. We observed an impairment of the hemorheological pattern in young patients with myocardial infarction, partially influenced by the infarction type (STEMI and NSTEMI) and persisting in the long term. PMID- 29792064 TI - The effect and importance of physical activity on behavioural and psychological symptoms in people with dementia: A systematic mixed studies review. AB - Background People with dementia may benefit from the effect of physical activity on behavioural and psychological symptoms of dementia. Qualitative synthesis of the importance of physical activity might complement and help clarify quantitative findings on this topic. The purpose of this systematic mixed studies review was to evaluate findings from both quantitative and qualitative methods about the effect and importance of physical activity on behavioural and psychological symptoms of dementia in people with dementia. Methods The systematic literature search was conducted in EMBASE, CINAHL, PubMed, PEDro and PsycINFO. Inclusion criteria were: people with a light to moderate degree of dementia, interventions including physical activity and outcomes focusing on behavioural and psychological symptoms of dementia or quality of life. To assess the methodological quality of the studies, the AMSTAR and GRADE checklists were applied for the quantitative studies and the CASP qualitative checklist for the qualitative studies. Results A small reduction in depression level and improved mood were seen in some quantitative studies of multi-component physical activity interventions, including walking. Due to high heterogeneity in the quantitative studies, a single summary of the effect of physical activity on behavioural and psychological symptoms of dementia should be interpreted with some caution. Across the qualitative studies, the common themes about the importance of physical activity were its 'socially rewarding' nature, the 'benefits of walking outdoors' and its contribution to 'maintaining self-hood'. Conclusion For people with dementia, there was a small, quantitative effect of multi-component physical activity including walking, on depression level and mood. People with dementia reported the importance of walking outdoors, experiencing the social rewards of physical activity in groups, as well as physical activity were a means toward maintaining self-hood. PMID- 29792063 TI - Integrating childhood obesity resources into the patient-centered medical home: Provider perspectives in the United States. AB - Pediatric primary care providers play a critical role in managing obesity yet often lack the resources and support systems to provide effective care to children with obesity. The objective of this study was to identify system-level barriers to managing obesity and resources desired to better managing obesity from the perspective of pediatric primary care providers. A 64-item survey was electronically administered to 159 primary care providers from 26 practices within a large pediatric primary care network. Bivariate analyses were performed to compare survey responses based on provider and practice characteristics. Also factor analysis was conducted to determine key constructs that effect pediatric interventions for obesity. Survey response rate was 69% ( n = 109), with the majority of respondents being female (77%), physicians (67%), and without prior training in obesity management (74%). Time constraints during well visits (86%) and lack of ancillary staff (82%) were the most frequently reported barriers to obesity management. Information on community resources (99%), an on-site dietitian (96%), and patient educational materials (94%) were most frequently identified as potentially helpful for management of obesity in the primary care setting. Providers who desired more ancillary staff were significantly more likely to practice in clinics with a higher percentage of obese, Medicaid, and Hispanic patients. Integrating ancillary lifestyle expert support into primary care practices and connecting primary care practices to community organizations may be a successful strategy for assisting primary care providers with managing childhood obesity, especially among vulnerable populations. PMID- 29792065 TI - Impaired sleep predicts onset of low back pain and burnout symptoms: evidence from a three-wave study. AB - In a three-wave questionnaire study of 405 working participants, who were initially free of low back pain (LBP) and emotional exhaustion, sleep problems were evaluated as a potential risk factor for the development of LBP and burnout up to three years later. Prospective risk paths were compared between the sexes and between two age-groups (18 to 45 years and older than 45 years). A longitudinal structural equation model showed a good fit with empirical data (RMSEA = .04, SRMR = .06, CFI = .97). Prospective risk paths between the latent constructs showed sleep problems to significantly predict self-reported LBP (beta = .15, p = .011) and burnout (beta = .24, p < .001) two years later. Sleep problems also predicted the occurrence of burnout three years later (beta = .18, p = .002). Sleep-related risk of burnout after two years was greater in older than younger participants (betaolder = .42 vs. betayounger = .13, p < .001). Sleep problems seem to precede LBP and burnout in working individuals. Health promotion initiatives should use sleep quality as an important early risk indicator, and interventions should focus on promoting better quality sleep, in an attempt to reduce the incidence of LBP and burnout. PMID- 29792066 TI - Capabilities of Next-Generation Patch Pump: Improved Precision, Instant Occlusion Detection, and Dual-Hormone Therapy. AB - Insulin pumps allow patients to attain better blood glucose control with more lifestyle flexibility. Their size and cost, however, limit their usefulness. Current CSII pumps are bulky, intrusive, and expensive. SFC Fluidics is addressing these problems by developing a new type of wearable patch pump based on the patented electro-chemiosmotic (ECO) microfluidic pumping technology. This nonmechanical pumping technology allows accurate and precise delivery of very small amounts of insulin and/or other drugs, including concentrated insulin. The pump engine is small and can be made inexpensively from injection molded parts, allowing its use in a disposable or semidisposable pod format. In addition, a single ECO pump engine can be used to deliver two drugs through independent pathways. Other features of SFC Fluidics' pod include latching safety valves that prevent accidental overdosing of insulin due to pressure changes and an instantaneous occlusion sensor that can immediately detect delivery failure at the first missed dose. These features allow for the development of a series of patch pumps that will offer users the benefit of CSII therapy in a more discreet and reliable patch pump form. PMID- 29792067 TI - Application of Machine Learning to Predict Dietary Lapses During Weight Loss. AB - BACKGROUND: Individuals who adhere to dietary guidelines provided during weight loss interventions tend to be more successful with weight control. Any deviation from dietary guidelines can be referred to as a "lapse." There is a growing body of research showing that lapses are predictable using a variety of physiological, environmental, and psychological indicators. With recent technological advancements, it may be possible to assess these triggers and predict dietary lapses in real time. The current study sought to use machine learning techniques to predict lapses and evaluate the utility of combining both group- and individual-level data to enhance lapse prediction. METHODS: The current study trained and tested a machine learning algorithm capable of predicting dietary lapses from a behavioral weight loss program among adults with overweight/obesity (n = 12). Participants were asked to follow a weight control diet for 6 weeks and complete ecological momentary assessment (EMA; repeated brief surveys delivered via smartphone) regarding dietary lapses and relevant triggers. RESULTS: WEKA decision trees were used to predict lapses with an accuracy of 0.72 for the group of participants. However, generalization of the group algorithm to each individual was poor, and as such, group- and individual-level data were combined to improve prediction. The findings suggest that 4 weeks of individual data collection is recommended to attain optimal model performance. CONCLUSIONS: The predictive algorithm could be utilized to provide in-the-moment interventions to prevent dietary lapses and therefore enhance weight losses. Furthermore, methods in the current study could be translated to other types of health behavior lapses. PMID- 29792068 TI - Loneliness, life satisfaction and psychological distress among out-of-school adolescents in a Nigerian urban city. AB - Loneliness is the feeling of distress that arises when an individual perceives his or her social relationships as being less satisfying than what is desired. Life satisfaction is a global assessment of an individual's quality of life based on his chosen criteria. This descriptive cross sectional study assessed loneliness, life satisfaction and psychological distress among 480 out of school adolescents using the UCLA loneliness scale, the Satisfaction with life scale (SWLS) and the General Health questionnaire. Reasons for out of school are poverty (45.0%), eager to do business (30.0%) and death of parents (20.0%). 25.8% experienced frequent loneliness while 24.2% had psychological distress. Findings were discussed in line with literature reviewed and recommendations made. PMID- 29792070 TI - Chondral Delamination of Fresh Osteochondral Allografts after Implantation in the Knee: A Matched Cohort Analysis. AB - Introduction Delamination of the chondral surface of an osteochondral allograft (OCA) from the underlying cancellous bone has been described as a mode of failure after implantation in the knee. Our hypothesis was that increased storage time of the OCA is associated with increased risk of graft delamination after implantation. Methods Prospective data on 13 patients with evidence of OCA delamination identified on magnetic resonance imaging or during subsequent surgery from 2000 to 2015 were reviewed. A cohort of 33 patients without evidence of graft delamination were then matched to the delamination group based on recipient age, sex, body mass index (BMI), and chondral defect location. The matched cohort size was established based on a power calculation for determining differences in OCA storage times. All patients had a minimum 2-year follow-up. Results There was no difference in donor age, donor sex, and graft storage time between groups (30 vs. 31 days, P = 0.78). There were no differences between number of previous ipsilateral knee surgeries (1.8 vs. 0.84, P = 0.26), BMI (26.8 vs. 25.0 kg/m2, P = 0.31), total chondral defect size (6.5 vs. 5.8 cm2, P = 0.41) or preoperative Marx activity scores between groups. Conclusion There is no association between OCA storage time, activity level scores, or number of previous ipsilateral knee surgeries and graft delamination in our patient population. Further work is needed to identify the etiology for this mode of failure of OCAs. PMID- 29792069 TI - Maternal nutrition and the developmental origins of osteoporosis in offspring: Potential mechanisms and clinical implications. AB - Osteoporosis, the most frequent metabolic disorder of bone, is a complex disease with a multifactorial origin that is influenced by genes and environments. However, the pathogenesis of osteoporosis has not been fully elucidated. The theory of "Developmental Origins of Health and Disease" indicates that early life environment exposure determines the risks of cardiometabolic diseases in adulthood. However, investigations into the effects of maternal nutrition and nutrition exposure during early life on the development of osteoporosis are limited. Recently, emerging evidence has strongly suggested that maternal nutrition has long-term influences on bone metabolism in offspring, and epigenetic modifications maybe the underlying mechanisms of this process. This review aimed to address maternal nutrition and its implications for the developmental origins of osteoporosis in offspring. It is novel in providing a theoretical basis for the early prevention of osteoporosis. Impact statement Our review aimed to address maternal nutrition and its implications for the developmental origins of osteoporosis in offspring, that can novelly provide a theoretical basis for the early prevention of osteoporosis. PMID- 29792071 TI - Phosphoramidates and phosphonamidates (ProTides) with antiviral activity. AB - Following the first report on the nucleoside phosphoramidate (ProTide) prodrug approach in 1990 by Chris McGuigan, the extensive investigation of ProTide technology has begun in many laboratories. Designed with aim to overcome limitations and the key resistance mechanisms associated with nucleoside analogues used in the clinic (poor cellular uptake, poor conversion to the 5' monophosphate form), the ProTide approach has been successfully applied to a vast number of nucleoside analogues with antiviral and anticancer activity. ProTides consist of a 5'-nucleoside monophosphate in which the two hydroxyl groups are masked with an amino acid ester and an aryloxy component which once in the cell is enzymatically metabolized to deliver free 5'-monophosphate, which is further transformed to the active 5'-triphosphate form of the nucleoside analogue. In this review, the seminal contribution of Chris McGuigan's research to this field is presented. His technology proved to be extremely successful in drug discovery and has led to two Food and Drug Administration-approved antiviral agents. PMID- 29792072 TI - Contextualizing acculturative stress among Latino immigrants in the United States: a systematic review. AB - PURPOSE: This systematic review of the literature informed of (a) the relationship between acculturation and acculturative stress, (b) examined the determinants of acculturative stress among Latino immigrants in the U.S., and (c) provided a conceptual framework that can be used to specify the interactive effect of various factors on acculturative stress. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review synthesized the results of thirty studies published between 2000 and 2015 that investigated the influence of several socio-demographic and cultural contexts on acculturative stress among Latino immigrants categorized using Family Stress Management (FSM) theory as a framework. RESULTS: Studied highlighted several protectors from and risks to acculturative stress. Historical context protective factors included having a choice over the decision to migrate and social support; risks included discrimination, family left abroad, and fear of deportation. Economic context protective factors included higher income. The development context protective factors included English skills, years in the U.S., and being married; risks included being female. Cultural context protective factors included being culturally competent and acculturation; risks included family cultural conflict and ethnic enclave pressures. Internal context protectors included post-immigration religious coping, church attendance, and family values. IMPLICATIONS: The results highlighted incorporating cultural aspects (i.e. family values and social support) in mental health practice with Latino immigrants. A less stressful integration experience can be achieved if age-related stressors and experiences of discrimination are acknowledged and the need for social support and harmonious family dynamics was prioritized in service plans. PMID- 29792073 TI - Burnout and depressive symptoms are not primarily linked to perceived organizational problems. AB - In this 257-participant study (76% female; mean age: 44.84), we examined two ideas that are widespread among burnout researchers: (a) the idea that burnout is primarily related to occupational-level factors; and (b) the idea that burnout should be considered a sentinel indicator in research on negative occupational outcomes. We investigated the links between burnout and a series of generic and work-related variables, namely, depressive symptoms, neuroticism, extraversion, effort-reward imbalance in the job [ERI], social support at work (SSW), and turnover intention. Burnout was assessed with the Shirom-Melamed Burnout Measure, depressive symptoms with the PHQ-9, neuroticism and extraversion with the NEO Five Factor Inventory, ERI with the 10-item version of the Effort-Reward Imbalance Questionnaire, SSW with the Job Content Questionnaire, and turnover intention with a dedicated 3-item measure. Correlation, multiple regression, and relative weight analyses were conducted. Burnout was not found to be more strongly linked to organizational and work-contextualized variables than to personality traits. In addition, turnover intention was not associated to a greater extent with burnout than with ERI. Burnout and depressive symptoms were highly correlated and exhibited overlapping nomological networks. Overall, our findings question the way burnout has been generally conceived. PMID- 29792074 TI - Lessons learned conducting a multi-center trial with a military population: The Tinnitus Retraining Therapy Trial. AB - Background The Tinnitus Retraining Therapy Trial (TRTT), a randomized, placebo controlled, multi-center trial, evaluated the efficacy of tinnitus retraining therapy and its individual components, tinnitus-specific educational counseling and sound therapy versus the standard of care, in military practice to improve study participants' quality of life. The trial was conducted at six US military hospitals to take advantage of the greater prevalence of tinnitus in the military population. Methods During the trial, various challenges arose that were uniquely related to the military setting. To convey these challenges to investigators planning future multi-center trials in military hospitals, we itemized various challenges that arose during the trial, interviewed clinic directors and coordinators to elicit their viewpoints, and then collated and organized their responses, together with those challenges presented while conducting the Tinnitus Retraining Therapy Trial. Results We encountered challenges in site selection, the approval process, administrative issues, study personnel training and retention, participant recruitment methods and issues, adherence to protocol, reimbursement issues, and military security. Site selection involved visiting 20 military hospitals to identify six sites that enrolled and followed study participants. We found that commitment for the trial must be obtained from the full military chain of command, but with ongoing changes in staff or military priorities, initial commitments were insufficient to sustain support throughout the entire trial. More time is required to obtain necessary administrative approvals by various military authorities and institutional review boards than is typically experienced in civilian settings. Recruitment strategies must be flexible due to changing military regulations regarding display of materials. Protracted periods of inactivity were due to sequestration and delays in institutional review board approval of required study personnel or protocol amendments. While mostly adherent to the protocol, study staff had difficulties in integrating study visits into the military clinical schedule. Unexpected study expenses revolved around hiring civilian study staff and obtaining associated security clearance while maintaining a consistent flow of funds to each site. The added expense negated cost savings realized by conducting the National Institutes of Health-funded trial at federal institutions, whose personnel could not be reimbursed for their efforts. Military security concerns impacted the use of web based data systems and led to increased time and effort required for site visits. Conclusion Overall, US military hospitals provide a unique setting to conduct multi-center trials. Challenges arise mainly due to ever-changing authority personnel and military priorities. Pre-planning and flexibility are keys in overcoming these challenges. Multi-center trials conducted in the military will likely take longer to initiate and complete than those in the civilian sector due to multiple levels of command and administrative approvals. PMID- 29792075 TI - Cancer/health communication and breast/cervical cancer screening among Asian Americans and five Asian ethnic groups. AB - OBJECTIVES: This paper is an examination of cancer/health communication factors (i.e. cancer/health information seeking, patient-provider communication (PPC), cancer screening information from providers) and screening for breast and cervical cancer among Asian Americans and five Asian ethnic groups (Chinese, Filipinos, Japanese, Koreans, Vietnamese) in comparison to Whites. Additionally, the relationship between cancer/health communication disparity and cancer screening gaps between Asian Americans and Whites was investigated. DESIGN: Data comes from a nationally representative sample of 2011-2014 Health Information National Trends Surveys (HINTS). RESULTS: Asian Americans and most Asian ethnic groups reported significantly lower rates of cancer/health information seeking and lower evaluations for PPC as compared to Whites, though differences within Asian ethnic groups were observed (Koreans' greater cancer/health information seeking, Japanese' higher PPC evaluation). When the cancer/health communication factors were controlled, Asian Americans' odds of cancer screening were increased. Especially, Asian Americans' odds of adhering to the breast cancer screening guideline became nearly 1.4 times greater than Whites. CONCLUSION: This research demonstrates that health organizations, providers, and Asian American patients' collaborative efforts to increase the access to quality cancer information, to make culturally competent but straightforward screening recommendations, and to practice effective communication in medical encounters will contribute to diminishing cancer disparities among Asian Americans. PMID- 29792076 TI - Emotion regulation in autism: Reappraisal and suppression interactions. AB - Emotion regulation has been proposed to be a transdiagnostic factor in the development and maintenance of psychopathology in the general population, yet the nature of the relationships between emotion regulation strategy use and psychological well-being has not been comprehensively explored in individuals with autism spectrum disorder (ASD). The aim of this study was to assess how the individual differences in self-reported emotion regulation strategy use relate to levels of both positive and negative psychological well-being. In total, 56 individuals with ASD aged 14-24 years (Mage = 18.15; SDage = 2.30) completed Emotion Regulation Questionnaire, Diagnostic and Statistical Manual of Mental Disorders-5 Generalized Anxiety Disorder Dimensional Scale, Patient Health Questionnaire-9, Warwick-Edinburgh Mental Well-being Scale and Autism-Spectrum Quotient - Short. Individuals were grouped into four clusters based on their Emotion Regulation Questionnaire subscale scores. Individuals in the high suppression and low reappraisal group expressed higher depressive symptoms and lower positive well-being when compared with the low suppression and high reappraisal group. Interestingly, individuals who self-reported using both high suppression and reappraisal expressed relatively high positive well-being and low depression symptoms. We suggest that the maladaptive effect of habitual suppression usage may be buffered by the habitual use of reappraisal, and this interaction between adaptive and maladaptive emotion regulation strategy use has clinical implications. PMID- 29792077 TI - Symptoms of PTSD in Frontline Journalists: A Retrospective Examination of 18 Years of War and Conflict. AB - OBJECTIVE: The objective of the current study was to determine the frequency and severity of symptoms of posttraumatic stress disorder (PTSD) in journalists covering conflict. METHODS: PTSD data (Impact of Event Scale-Revised) collected over an 18-year period from 684 conflict journalists were analyzed retrospectively for frequency and severity of reexperiencing, avoidance, and arousal symptoms. Conflicts covered were civil wars in the Balkans ( n = 140 journalists), 9/11 attack in New York City ( n = 46), Iraq war ( n = 84), Mexico drug wars ( n = 104), civil war in Syria ( n = 59), Kenya election violence/Al Shabab terror ( n = 57), state-sanctioned media intimidation in Iran ( n = 114), and the current migration crisis in Europe ( n = 80). RESULTS: The mean age of the sample was 38.59 (SD = 8.35) years, 461 (67%) journalists were men, and the mean duration of conflict work was 13.42 (SD = 7.74) years. The 5 most frequently endorsed symptoms were in the reexperiencing/intrusion category. Mean intrusion (1.31, SD = 0.97), avoidance (1.08, SD = 0.89), and arousal (1.07, SD = 0.96) scores for the entire sample were in the mild range. Being female and less educated independently predicted PTSD symptoms. CONCLUSIONS: PTSD phenomenology in a group of conflict journalists with well over a decade of frontline experience is dominated by reexperiencing symptoms. While symptom severity is for the most part mild, group means can obscure those individuals with significantly more severe difficulties. PMID- 29792078 TI - Ethical values of academic nurses: A pilot study. AB - BACKGROUND: While academics contribute to the development of society through all the subjects that they work on, they also have other important tasks to fulfill, such as being role models for their students and society. Therefore, the place of academic ethical values is a significant topic for academic nurses. OBJECTIVE: The main objective of this research was to examine the attitudes of academic nurses toward academic ethics. RESEARCH DESIGN: This descriptive and cross sectional research study was conducted between March and June 2017 in three different public universities in Turkey. The research sample consisted of 132 nurses in different professional positions at different universities who volunteered to participate in the study. The data were collected with an Information Form and an Academic Ethical Values Scale developed in Turkey. Ethical considerations: Ethical approval was granted by the institutions involved, and all participants provided informed verbal consent. FINDINGS: The attitudes of academics participating in the research on academic ethical values were found to be highly positive. When the sub-dimensions of the scale were examined, the dimension with the highest average attitudinal score is found to be "values regarding the teaching process" and the dimension with the lowest average attitude score is found to be "values regarding society." Depending on the participants' academic position, it was determined that the total average score for the Academic Ethical Values Scale and the average scores of the "values regarding scientific research" and "values regarding the teaching process" sub dimensions differed significantly (p < 0.05). CONCLUSION: It was found that academic nurses had highly positive attitudes of toward academic ethical values. It can be argued that academics act more responsibly with regard to the ethical values of the teaching process than other areas. In addition, academics who are professors are most sensitive in their perception of academic ethical values. PMID- 29792080 TI - Stakeholders' resistance to telemedicine with focus on physicians: utilizing the Delphi technique. AB - Introduction Sufficient infrastructure for information and communications technology (ICT) and a well-established policy are necessary factors for smooth implementation of telemedicine. However, despite these necessary conditions being met, there are situations where telemedicine still fails to be accepted as a system due to the low receptivity of stakeholders. In this study, we analyse stakeholders' resistance to an organization's implementation of telemedicine. Focusing on the physicians' interests, we propose a strategy to minimize conflicts and improve acceptance. Methods The Delphi study involved 190 telemedicine professionals who were recommended by 485 telemedicine-related personnel in South Korea. Results Out of 190 professionals, 60% of enrolled participants completed the final questionnaires. The stakeholders were categorized into four groups: policy-making officials, physicians, patients, and industrialists. Among these, the physicians were most opposed to the adoption of telemedicine. The main causes of such opposition were found to be the lack of a medical services delivery system and the threat of disruption for primary care clinics. Very little consensus was observed among the stakeholders, except on the following points: the need for expansion of the national health insurance budget by the government, and the need for enhancement of physicians' professional autonomy to facilitate smooth agreements. Discussion Our analysis on the causes of the resistance to telemedicine, carried out with the groups mentioned above, has important implications for policy-makers deriving strategies to achieve an appropriate consensus. PMID- 29792079 TI - Parent perspectives of neonatal tele-homecare: A qualitative study. AB - Introduction Neonatal homecare for preterm infants is a method of supporting families and monitoring infant growth in the home setting. Telehealth may be used to deliver specialist neonatal care remotely, using online communication methods. This study explored parental experiences with neonatal tele-homecare (NTH). Methods Semi-structured interviews were conducted with 49 parents whose preterm infants had received NTH from a neonatal intensive care unit (NICU) in Denmark. Interview transcripts were analysed using Malterud's systematic text condensation. Results Parents experienced NTH as a personalised method for linking to specialist staff in the NICU. NTH promoted the parent's role as the primary care provider, further strengthening the parent-infant relationship. Discussion From the perspective of parents with preterm infants requiring specialist care, NTH is a useful method of supporting families in the home. Telehealth provides effective communication links with NICU specialists and encourages family-centred care. PMID- 29792082 TI - Mining concepts of health responsibility using text mining and exploratory graph analysis. AB - BACKGROUND: Occupational therapists need to know about people's beliefs about personal responsibility for health to help them pursue everyday activities. AIM: The study aims to employ state-of-the-art quantitative approaches to understand people's views of health and responsibility at different ages. METHODS: A mixed method approach was adopted, using text mining to extract information from 233 interviews with participants aged 5 to 96 years, and then exploratory graph analysis to estimate the number of latent variables. The fit of the structure estimated via the exploratory graph analysis was verified using confirmatory factor analysis. RESULTS: Exploratory graph analysis estimated three dimensions of health responsibility: (1) creating good health habits and feeling good; (2) thinking about one's own health and wanting to improve it; and 3) adopting explicitly normative attitudes to take care of one's health. The comparison between the three dimensions among age groups showed, in general, that children and adolescents, as well as the old elderly (>73 years old) expressed ideas about personal responsibility for health less than young adults, adults and young elderly. CONCLUSIONS: Occupational therapists' knowledge of the concepts of health responsibility is of value when working with a patient's health, but an identified challenge is how to engage children and older persons. PMID- 29792081 TI - Efficacy of a Word- and Text-Based Intervention for Students With Significant Reading Difficulties. AB - We examine the efficacy of an intervention to improve word reading and reading comprehension in fourth- and fifth-grade students with significant reading problems. Using a randomized control trial design, we compare the fourth- and fifth-grade reading outcomes of students with severe reading difficulties who were provided a researcher-developed treatment with reading outcomes of students in a business-as-usual (BAU) comparison condition. A total of 280 fourth- and fifth-grade students were randomly assigned within school in a 1:1 ratio to either the BAU comparison condition ( n = 139) or the treatment condition ( n = 141). Treatment students were provided small-group tutoring for 30 to 45 minutes for an average of 68 lessons (mean hours of instruction = 44.4, SD = 11.2). Treatment students performed statistically significantly higher than BAU students on a word reading measure (effect size [ES] = 0. 58) and a measure of reading fluency (ES = 0.46). Though not statistically significant, effect sizes for students in the treatment condition were consistently higher than BAU students for decoding measures (ES = 0.06, 0.08), and mixed for comprehension (ES = -0.02, 0.14). PMID- 29792083 TI - A systematic review and meta-analysis of the association between vitamin A intake, serum vitamin A, and risk of liver cancer. AB - BACKGROUND: Previous evidence supports that vitamin A decreases the risk of several types of cancer. However, the association between vitamin A and liver cancer is inconclusive. AIM: This systematic review and meta-analysis summarizes the existing literature, discussing the association between vitamin A intake, serum vitamin A, and liver cancer in adult populations. METHODS: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to vitamin A (e.g. retinol, alpha-carotene, beta-carotene, and beta-cryptoxanthin) and hepatic cancer without applying any time restriction. A meta-analysis was performed using random effect models. RESULTS: The meta-analysis of five studies showed no association between serum retinol and liver cancer (pooled risk ratio = 1.90 (0.40-9.02); n = 5 studies, I2 = 92%). In addition, the systematic review of studies from 1955 to July 2017 found studies that indicated no association between the intake and serum level of alpha-carotene ( n = 2) and beta cryptoxanthin ( n = 1) and the risk of liver cancer. Further, the associations between retinol intake ( n = 3), beta-carotene intake ( n = 3), or serum beta carotene ( n = 3) and liver cancer were inconclusive. CONCLUSIONS: Current information on the association between vitamin A intake and liver cancer or serum vitamin A and liver cancer are limited. Most studies demonstrated no association between dietary vitamin A and the risk of liver cancer. However, the finding was based on a small number of studies with potential publication bias. Therefore, large observational studies should be conducted to confirm these associations. PMID- 29792084 TI - Lethal disseminated tuberculosis in patients under biological treatment - two clinical cases and a short review. AB - Tumour necrosis factor (TNF)-alpha inhibitors are highly used in Romania for the treatment of autoimmune disorders, such as rheumatoid arthritis (RA), psoriasis, inflammatory bowel diseases, and ankylosing spondylitis. Biological therapy using TNF-alpha inhibitors is very effective but is associated with an increased risk of opportunistic infections, including active tuberculosis. Here, two cases are presented of patients with RA and psoriasis under biological therapy who developed very aggressive forms of disseminated tuberculosis, with a rapid progression to death. The authors conclude that patients undergoing biological therapy require thorough evaluation prior to initiating treatment, followed by continuous and rigorous monitoring by a multidisciplinary team during biological treatment, particularly in countries with a high incidence of tuberculosis. PMID- 29792085 TI - Role of selenium supplementation in prevention of late onset sepsis among very low birth weight neonates: a systematic review of randomized controlled trials. AB - BACKGROUND: Neonatal sepsis is one of the most common causes of neonatal morbidity and mortality. Selenium has antioxidant and immune-modulating properties. AIM: The aim of this systematic review is to evaluate role of selenium supplementation in the prevention of late onset sepsis (LOS) among very low birth weight (VLBW) neonates. METHODS: We searched literature for this review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) electronic PubMed, Embase, and Google Scholar. We also searched for ongoing clinical trials. RESULTS: This review included two randomized controlled trials (RCTs) that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of LOS in the intervention group [23.7 versus 35.6%; relative risk (RR) 0.67; 95% CI 0.52-0.86; p= .001; number needed to treat (NNT) 8.4; 95% CI 5.2-20.96]. However, mortality due to any cause prior to hospital discharge was not statistically significant in between the groups (6.1% intervention group versus 6.9% control group; RR 0.88; 95% CI 0.49-1.61; p= .68). CONCLUSIONS: Evidences from current systematic review revealed that selenium supplementation has some role in the prevention of LOS. However, due to limited evidences and heterogeneity between studies, large RCTs are recommended among VLBW neonates. PMID- 29792087 TI - Effects of intensive short-term dynamic psychotherapy on social cognition in major depression. AB - BACKGROUND: Social cognition is commonly affected in psychiatric disorders and is a determinant of quality of life. However, there are few studies of treatment. OBJECTIVE: To investigate the efficacy of intensive short-term dynamic psychotherapy on social cognition in major depression. METHOD: This study used a parallel group randomized control design to compare pre-test and post-test social cognition scores between depressed participants receiving ISTDP and those allocated to a wait-list control group. Participants were adults (19-40 years of age) who were diagnosed with depression. We recruited 32 individuals, with 16 participants allocated to the ISTDP and control groups, respectively. Both groups were similar in terms of age, sex and educational level. RESULTS: Multivariate analysis of variance (MANOVA) demonstrated that the intervention was effective in terms of the total score of social cognition: the experimental group had a significant increase in the post-test compared to the control group. In addition, the experimental group showed a significant reduction in the negative subjective score compared to the control group as well as an improvement in response to positive neutral and negative states. CONCLUSION: Depressed patients receiving ISTDP show a significant improvement in social cognition post treatment compared to a wait-list control group. PMID- 29792088 TI - Experimental evaluation of ontology-based HIV/AIDS frequently asked question retrieval system. AB - This study presents the results of experimental evaluations of an ontology-based frequently asked question retrieval system in the domain of HIV and AIDS. The main purpose of the system is to provide answers to questions on HIV/AIDS using ontology. To evaluate the effectiveness of the frequently asked question retrieval system, we conducted two experiments. The first experiment focused on the evaluation of the quality of the ontology we developed using the OQuaRE evaluation framework which is based on software quality metrics and metrics designed for ontology quality evaluation. The second experiment focused on evaluating the effectiveness of the ontology in retrieving relevant answers. For this we used an open-source information retrieval platform, Terrier, with retrieval models BM25 and PL2. For the measurement of performance, we used the measures mean average precision, mean reciprocal rank, and precision at 5. The results suggest that frequently asked question retrieval with ontology is more effective than frequently asked question retrieval without ontology in the domain of HIV/AIDS. PMID- 29792086 TI - Risk of further surgery on the same or opposite side and mortality after primary total hip arthroplasty: A multi-state analysis of 133,654 patients from the Swedish Hip Arthroplasty Register. AB - Background and purpose - The hip-related timeline of patients following a total hip arthroplasty (THA) can vary. Ideally patients will live their life without need for further surgery; however, some will undergo replacement on the contralateral hip and/or reoperations. We analyzed the probability of mortality and further hip-related surgery on the same or contralateral hip. Patients and methods - We performed a multi-state survival analysis on a prospectively followed cohort of 133,654 Swedish patients undergoing an elective THA between 1999 and 2012. The study used longitudinally collected information from the Swedish Hip Arthroplasty Register and administrative databases. The analysis considered the patients' sex, age, prosthesis type, surgical approach, diagnosis, comorbidities, education, and civil status. Results - During the study period patients were twice as likely to have their contralateral hip replaced than to die. However, with passing time, probabilities converged and for a patient who only had 1 non-revised THA at 10 years, there was an equal chance of receiving a second THA and dying (24%). It was 8 times more likely that the second hip would become operated with a primary THA than that the first hip would be revised. Multivariable regression analysis reinforced the influence of age at operation, sex, diagnosis, comorbidity, and socioeconomic status influencing state transition. Interpretation - Multi-state analysis can provide a comprehensive model of further states and transition probabilities after an elective THA. Information regarding the lifetime risk for bilateral surgery, revision, and death can be of value when discussing the future possible outcomes with patients, in healthcare planning, and for the healthcare economy. PMID- 29792089 TI - Retrieval of a migrated N-butyl-2 cyanoacrylate cast using a snare-kit system during dural AVF embolization: A case report. AB - N-butyl-2 cyanoacrylate (NBCA) is a liquid embolic material that is widely used in various endovascular procedures because of its permanent and rapid vascular occluding effect regardless of the coagulation profile of the patient. However, NBCA migration to unintended vessels may result in serious complications. This report describes the retrieval of a migrated NBCA cast from the transverse sigmoid sinus during dural arteriovenous fistula embolization using a transvenous snaring technique. PMID- 29792092 TI - The Relationship Between Narcissism and Personality Traits of the Five-Factor Model in Adolescents and Young Adults. AB - Narcissism is seen as a multidimensional construct that consists of two manifestations: grandiose and vulnerable narcissism. In order to define these two manifestations, their relationship to personality factors has increasingly become of interest. However, so far no studies have considered the relationship between different phenotypes of narcissism and personality factors in adolescents. Method: In a cross-sectional study, we examine a group of adolescents ( n = 98; average age 16.77 years; 23.5 % female) with regard to the relationship between Big Five personality factors and pathological narcissism using self-report instruments. This group is compared to a group of young adults ( n = 38; average age 19.69 years; 25.6 % female). Results: Grandiose narcissism is primarily related to low Agreeableness and Extraversion, vulnerable narcissism to Neuroticism. We do not find differences between adolescents and young adults concerning the relationship between grandiose and vulnerable narcissism and personality traits. Discussion: Vulnerable and grandiose narcissism can be well differentiated in adolescents, and the pattern does not show substantial differences compared to young adults. PMID- 29792091 TI - Rete mirabile of the ICA: Report of three cases. AB - Carotid rete mirabile is an arterial meshwork, occurring at the cavernous portion of the internal carotid artery (ICA). Rete mirabile in humans is not present during normal development of the intracranial circulation and hence is considered as a collateral pathway that develops as a consequence of segmental agenesis of the ICA. We report three cases of this rare entity encountered at our institute. PMID- 29792090 TI - Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke. AB - Objective Embolism due to coagulopathy might be the main pathomechanism underlying cancer-related stroke (CRS). CRS patients with a large artery occlusion could be candidates for endovascular recanalization therapy (ERT), although its procedural and clinical outcomes are not well known. This study aimed to investigate the procedural and clinical outcomes of ERT in CRS patients and the characteristics associated with outcomes compared with those of conventional stroke patients. Methods A registry of consecutive acute ischemic stroke patients who underwent ERT between January 2011 and October 2015 was retrospectively reviewed. CRS patients are described as those who had (a) cryptogenic stroke with advanced or metastatic cancer; (b) no other possible causes of stroke such as cardioembolism (CE) and large artery atherosclerosis (LAA); and (c) elevated D-dimer levels or diffusion-restricted lesions in multiple vascular territories. We compared procedural and clinical outcomes at discharge among CRS, CE, and LAA patients. Results A total of 329 patients were finally enrolled in this study; of these, 19 were CRS patients. The rate of successful recanalization, defined as modified treatment in cerebral infarction grade 2b or 3, was lower in the CRS group than in the LAA and CE groups (63% versus 84% versus 84%, p = .06). CRS subtype was an independent predictor for successful recanalization after ERT in the multivariate analysis (odds ratio, 0.317; 95% confidence interval, 0.116-0.867; p < .001). No significant difference in the rate of good clinical outcomes at discharge was observed among groups. Conclusions Although clinical outcomes at discharge were similar for CE and LAA patients, complete recanalization seemed more difficult to achieve in CRS patients than in conventional stroke patients. PMID- 29792094 TI - Regulatory context and validation of assays for clinical mass spectrometry proteomics (cMSP) methods. AB - Clinical mass spectrometry proteomics (cMSP) assays are being increasingly used in clinical laboratories for analyzing peptides and proteins. It has therefore become urgent to characterize and validate the methods available for liquid chromatography-tandem mass spectrometry (LC/MS-MS) targeted quantification of peptide and protein biomarkers in biological fluids in the context of in vitro diagnostics. LC-MS/MS for the detection of peptides and proteins is currently the main approach used in the field of cMSP. As a result of their selectivity, low reagent costs and the fact that these methods can be used for absolute quantification and multiplexing, they will likely eventually replace immunoassays. Although LC-MS/MS is known to be the main reference method involved in reference measurement procedures (RMPs), it needs to meet the requirements of in vitro diagnostic (IVD) regulations and standards. This review shows that cMSP is fully compatible with the regulatory IVD requirements and provides an overview of the characterization and validation of the use of LC-MS/MS targeted quantification of clinical protein biomarkers in biological fluids. PMID- 29792095 TI - What is the effect of intertwin delivery interval on the outcome of the second twin delivered vaginally? AB - OBJECTIVE: Optimal management of twin deliveries is controversial. We aimed to assess if intertwin delivery interval, after vaginal delivery of the first twin, may have an influence on adverse neonatal outcomes of the second twin Study design: This is a retrospective observational study including diamniotic twin pregnancies with vaginal delivery of the first twin, between January 2000 and July 2017. Inclusion criteria were diamniotic pregnancies and vaginal delivery of the first twin. We excluded higher twin order, monoamniotic pregnancies, cesarean delivery of the first twin and patients with missing data. RESULTS: A number of 400 diamniotic twin pregnancies met the inclusion criteria and were divided, considering intertwin delivery interval into (1) <=30 minutes (n = 365); and (2) >30 minutes (n = 35). Considering the two study groups, maternal and first twin characteristics and outcomes were similar. Second twin reported higher incidence of cesarean section and vacuum delivery, but similar incidence of neonatal adverse outcomes, in case of intertwin interval >30 minutes. At multivariate analysis, a difference between second and first twin weight >=25% was correlated to neonatal adverse outcome, while we did not found this correlation with a cut off of 30 minutes. CONCLUSIONS: In our study, growth discrepancy between twins was significantly correlated to adverse neonatal outcomes, while intertwin delivery time was not an influencing factor. So, in line with this result, in our clinical practice, we do not use a fixed time in which both twins should be delivered, neither in monochorionic nor in dichorionic pregnancies, when fetal wellbeing was demonstrated during labor. PMID- 29792096 TI - Neonatal outcome in preterm deliveries before 34-week gestation - the influence of the mechanism of labor onset. AB - PURPOSE: To evaluate neonatal outcomes in preterm infants with less than 34 weeks after spontaneous labor, preterm premature rupture of membranes (PPROM) or iatrogenic delivery and to clarify whether the mechanism of labor onset is a risk factor for adverse short-term neonatal outcome. METHODS: We performed a retrospective case-control study, which included 266 preterm newborns with less than 34-week gestation, between 2011 and 2015. Neonatal outcomes were compared according to the mechanism of labor onset. Our primary outcomes were neonatal death, sequelae on hospital discharge and a composite of these two variables (combined neonatal outcome). RESULTS: Compared to spontaneous preterm labor, iatrogenic preterm newborns were at increased risk of respiratory distress syndrome (RDS) [Odds Ratio (OR) 3.05 (95%CI 1.31; 7.12)], and need of exogenous surfactant administration [OR 3.87 (95%CI 1.60; 9.35)]. PPROM was associated with higher risk of neonatal sepsis [OR 12.96 (95%CI 1.18; 142.67)]. There were no differences regarding the combined outcome for iatrogenic [OR 0.94 (95%CI 0.33; 2.71)] or PPROM [OR 1.11 (95%CI 0.35; 3.49)] groups. CONCLUSIONS: In our study, the different mechanisms of labor onset are associated with different neonatal outcomes. Iatrogenic preterm birth was associated with an increased risk of RDS and a higher need of exogenous surfactant administration than spontaneous group. The rate of neonatal sepsis was significantly higher in PPROM group along with a higher prevalence of histological chorioamnionitis. PMID- 29792097 TI - The effect of loneliness on depression: A meta-analysis. AB - BACKGROUND: Negative emotions, which have a common, chronic and recurrent structure, play a vital role in the development and maintenance of psychopathology. In this study, loneliness as a negative emotion was considered to be a predisposing factor in depression. AIM: The aim of this meta-analysis is to determine the effect of loneliness on depression. METHOD: Initially, a literature scan was performed and all related literature was pooled together ( n = 531). Based on scales determined by the researchers, it was decided to include 88 studies in the analysis. This study obtained a sampling group of 40,068 individuals. RESULTS: The results of using a random effects model for analysis showed that loneliness had a moderately significant effect on depression. None of the variables of study sampling group, type of publication and publication year were found to be moderator variables. CONCLUSION: According to the results of the research, loneliness may be said to be a significant variable affecting depression. The findings obtained are discussed in light of the literature. PMID- 29792098 TI - P-wave and QT dispersion in hypertensive disorders of pregnancy. AB - AIM: To compare P-wave and QT dispersion values in hypertensive disorders of pregnancy and controls and also in preeclampsia, chronic hypertension, and gestational hypertension separately. MATERIAL AND METHODS: We included 140 hypertensive pregnants and 110 healthy age-matched pregnants in this study. The hypertensive pregnants were divided into three subgroups: preeclampsia (n = 43), chronic hypertension (n = 51), and gestational hypertension (n = 46). P-wave and QT dispersion values were compared between groups. RESULTS: Hypertensive pregnants had higher P-wave (41.74 +/- 5.51 vs. 37.73 +/- 5.62, p < .001) and QTc dispersion (45.44 +/- 7.62 vs. 39.77 +/- 8.34, p < .001) values. In subgroup analysis, P-wave dispersion and QTc dispersion were different between preeclamptic, chronic hypertensive, and gestational hypertensive patients. Also, they were significantly higher in chronic hypertension as compared to gestational hypertension and they were higher in preeclampsia than in gestational hypertension. No difference was found according to these parameters between preeclampsia and chronic hypertension. In correlation analysis, both P-wave dispersion and QTc dispersion were positively correlated with systolic (r = 0.409, p < .001 and r = 0.306, p < .001) and diastolic blood pressure (r = 0.390, p < .001 and r = 0.287, p < .001) which are main clinical determinants of hypertensive disorders. CONCLUSION: In clinical practice, chronic hypertensive pregnants are generally followed up in their future life for cardiovascular disorders. Also, we recommend that we must inform and follow preeclamptic patients for future cardiovascular diseases. PMID- 29792099 TI - Speak up: Preparing for international clinical placements. PMID- 29792100 TI - Difficult debriefing situations: A toolbox for simulation educators. AB - BACKGROUND: Simulation-based education (SBE) has emerged as an essential modality for health professions education. One of the central tenants of effective SBE is reflective practice, typically guided by a facilitated debriefing. The debriefing conversation has the possibility of becoming a difficult conversation based on learner and situation-related factors. Difficult debriefing situations may threaten the learning environment, thus requiring an appreciation and understanding of the various ways that learners may react adversely to simulation and debriefing. AIM: This article provides a review of the various phenotypes of difficult debriefing situations and a toolbox of proactive and reactive strategies to help guide the simulation educator to manage these situations, with the ultimate goal of achieving learning objectives. PMID- 29792101 TI - Utility of a novel elastic traction system in endoscopic thyroidectomy via breast approach: initial experience with 34 patients. AB - Objective To summarize our experiences in using an elastic traction, space-making technique for endoscopic thyroidectomy via breast approach in the treatment of early-stage differentiated papillary thyroid carcinoma. Methods A retrospective analysis was performed on patients who underwent endoscopic thyroidectomy via breast approach for thyroid carcinoma in our department. We used our self developed "mini elastic traction space-maker" in a group of 34 patients; another 45 patients who underwent the procedure with the conventional CO2 insufflation method were enlisted as the control group. Results All patients had successful unilateral lobectomy and central lymph node dissection (CLND) surgeries. The adoption of the intraoperative elastic traction system increased the height of the subcutaneous working space (by 1 cm) and significantly decreased the times required for lobectomy and CLND compared with the controls (46.7 +/- 4.7 min vs. 50.7 +/- 4.9 min). However, there was no significant difference between the two groups in the set-up time to create the working space. Conclusions The elastic traction, space-making technique is a safe and feasible technique for endoscopic thyroidectomy via breast approach. PMID- 29792102 TI - Entrusting internal medicine residents to use point of care ultrasound: Towards improved assessment and supervision. AB - BACKGROUND: Internal medicine physicians and trainees are increasingly using, and seeking training in, diagnostic point of care ultrasound (POCUS). Numerous internal medicine training programs have described their curricula, but little has been written about how learners should be assessed, supervised, and allowed to progress toward independent practice, yet these practices are imperative for safe and effective use. Entrustable professional activities (EPAs) offer a practical method to assess observable units of professional work and make supervision decisions. METHODS: An EPA for POCUS is used as a framework to assess and determine appropriate levels of supervision in an internal medicine residency program. RESULTS: All learners have been able to advance to level 2 with a mandatory introductory boot camp course. Learners have been able to advance to higher levels of independence, often after taking formal elective programmatic coursework. However, not all learners taking the same coursework have been granted the same level of independence. CONCLUSIONS: It is feasible to assess and supervise internal medicine residents' ability to use diagnostic point of care ultrasound using an EPA. PMID- 29792103 TI - Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures. AB - BACKGROUND: Most preterm infants are exposed to a variable duration of antibiotic therapy after birth despite negative cultures. Data is emerging about the risks of prolonged antibiotics. We sought to assess the association between length of initial antibiotic course and neonatal outcomes in a cohort from a single large perinatal center. METHODS: Retrospective cohort study of prospectively collected data on all infants with a birth weight of less than 1250 g hospitalized in our NICU in a 4 year window and who had negative blood and CSF cultures in the first 2 days of life. The primary outcome is a composite of necrotizing enterocolitis (NEC), late onset sepsis (LOS) and death evaluated using multivariable regression analysis. RESULTS: A total of 620 infants less than 1250 g with negative cultures were eligible for study over a 4 year period. The 238 infants with more than 5 days initial antibiotic use were significantly smaller and of lower gestational age than the 382 infants who received up to 5 days of antibiotics. Their mothers had more clinical chorioamnionitis, less maternal hypertension and greater perinatal use of antibiotics. On multivariate analysis, infants who received empiric antibiotics for longer than 5 days had higher rates of neonatal morbidities after adjusting for gestational age, SNAP II, small-for-gestational age status, gender, maternal hypertension, prenatal steroid treatment, clinical chorioamnionitis, intrapartum antibiotic treatment, and multiple births. Composite outcome OR: 1.83 (1.15 to 2.92), LOS OR: 2.02 (1.20 to 3.39), bronchopulmonary dysplasia OR: 1.58 (1.04 to 2.29). Mortality and NEC were not significantly different. CONCLUSION: More than 5 days of antibiotic treatment in very preterm infants with negative cultures was associated with increased morbidity in our population, and that included BPD. It is of note that patterns of increased morbidity and/or mortality differ between studies. Prospective trials of clinical protocols for starting and stopping antibiotics in the very preterm infants are required. PMID- 29792104 TI - Association of Hip and Foot Factors With Patellar Tendinopathy (Jumper's Knee) in Athletes. AB - Background Investigations on the causes of patellar tendinopathy should consider impairments at the hip and foot/ankle because they are known to influence movement patterns and affect patellar tendon loading. Objectives To investigate hip and foot/ankle impairments associated with patellar tendinopathy in volleyball and basketball athletes using classification and regression tree analysis. Methods In this clinical measurement, cross-sectional study, 192 athletes were assessed for impairments of the hip and foot/ankle, including shank forefoot alignment, dorsiflexion range of motion (ROM), iliotibial band flexibility, passive hip internal rotation ROM, and hip external rotator and hip abductor isometric strength. Athletes with tenderness and/or pain at the inferior pole of the patella were considered to have patellar tendinopathy. Athletes with scores higher than 95 points on the Victorian Institute of Sport Assessment patella (VISA-P), no pain during the single-leg decline squat, and no history of patellar tendon pain were considered not to have patellar tendinopathy. Classification and regression tree analyses were performed to identify interacting factors associated with patellar tendinopathy. Results Interactions among passive hip internal rotation ROM, shank-forefoot alignment, and hip external rotator and abductor strength identified athletes with and without patellar tendinopathy. The model achieved 71.2% sensitivity and 74.4% specificity. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval: 0.70, 0.84; P<.001). Conclusion Impairments of the hip and foot/ankle are associated with the presence of patellar tendinopathy in volleyball and basketball athletes. Future studies should evaluate the role of these impairments in the etiology of patellar tendinopathy. J Orthop Sports Phys Ther 2018;48(9):676-684. Epub 23 May 2018. doi:10.2519/jospt.2018.7426. PMID- 29792105 TI - Risk Factors for Groin Injury and Groin Symptoms in Elite-Level Soccer Players: A Cohort Study in the Dutch Professional Leagues. AB - Background Groin injury and groin symptoms are common in soccer players. The relationship of groin injury and groin symptoms to reduced hip range of motion (ROM) and previous injury is unclear. Objectives To conduct a retrospective assessment of associations between previous injury and preseason hip ROM and preseason prevalence of severe groin symptoms, and to prospectively identify risk factors for within-season groin injury. Methods During the period of 2015 to 2016, 190 players from 9 Dutch professional soccer clubs participated in this cohort study with prospective and retrospective elements. Univariate and multivariate logistic regressions were used to predict preseason severe groin symptoms, identified using the Copenhagen Hip and Groin Outcome Score, from a history of previous groin injury, general injury (minimum of 1 week in duration) in the previous season, and hip ROM. Cox regression was used to predict within season groin injury. Results Point prevalence of severe groin symptoms was 24% and within-season incidence of groin injury was 11%. Total, training, and match groin injury incidences were 0.5, 0.2, and 2.6 injuries per 1000 playing hours, respectively. A history of more than 1 previous groin injury was associated with current severe groin symptoms (odds ratio = 3.0; 95% confidence interval: 1.0, 8.3; P = .038). General injury sustained in the previous season (ankle, knee, thigh, shoulder; median, 9 weeks of time loss) was a risk factor for groin injury (hazard ratio = 5.1; 95% confidence interval: 1.8, 14.6; P = .003). Conclusion Severe injuries in the previous season to locations other than the groin increase the risk of groin injury the next season. A history of groin injury is associated with current severe groin symptoms. Preseason hip ROM does not identify players at risk for groin injury. Level of Evidence Prevention, level 2b. J Orthop Sports Phys Ther 2018;48(9):704-712. Epub 23 May 2018. doi:10.2519/jospt.2018.7990. PMID- 29792106 TI - Psychometric Properties of the Photograph Series of Daily Activities-Short Electronic Version (PHODA-SeV) in Patients With Chronic Low Back Pain. AB - Background The Photograph Series of Daily Activities-short electronic version (PHODA-SeV) assesses perceived harmfulness of daily activities in patients with low back pain (LBP). Although there is some evidence that the PHODA-SeV is a reliable and valid tool, its psychometric properties have not been fully investigated. Objectives To investigate the test-retest reliability, measurement error, interpretability, construct validity, and internal and external responsiveness of the PHODA-SeV in patients with chronic LBP. Methods Ninety-one patients were included in the analysis for this prospective cohort study. For reliability purposes, the PHODA-SeV was administered twice, with a 1-week interval before beginning treatment. Pain, disability, and measures of pain related fear (ie, PHODA-SeV, Fear-Avoidance Beliefs Questionnaire [FABQ], and Tampa Scale of Kinesiophobia [TSK]) were collected before and after the 8-week treatment period. Results The PHODA-SeV showed excellent reliability (intraclass correlation coefficient model 2,1 = 0.91), without evidence of ceiling and floor effects. The construct validity analysis demonstrated fair correlations (r = 0.25 0.50) of the PHODA-SeV with the FABQ, but no correlation with the TSK (r<0.25). For internal responsiveness, the PHODA-SeV showed an effect size of 0.87 and a standardized response mean of 0.92, interpreted as a large effect (greater than 0.80). For external responsiveness, the correlations between the PHODA-SeV and changes in the TSK and FABQ were considered low, and the receiver operating characteristic curve analyses revealed an area under the curve lower than the proposed threshold of 0.70. Conclusion The PHODA-SeV is a reliable tool that can detect changes over time in pain-related fear in patients with chronic LBP undergoing physical therapy treatment. This tool, however, failed to identify those patients who did or did not improve, according to other pain-related fear measures. J Orthop Sports Phys Ther 2018;48(9):719-727. Epub 23 May 2018. doi:10.2519/jospt.2018.7864. PMID- 29792107 TI - Hand-Grip Strength: Normative Reference Values and Equations for Individuals 18 to 85 Years of Age Residing in the United States. AB - Background Hand-grip strength is an indicator of overall strength and a predictor of important outcomes. Up-to-date, population-specific reference values for measurements of grip strength are needed to properly interpret strength outcomes. Objectives To provide population-based grip-strength reference values and equations for US residents 18 to 85 years of age. Methods Hand-grip data from 1232 participants 18 to 85 years of age were extracted from the database of the 2011 normative phase of the US National Institutes of Health Toolbox project in this cross-sectional study. Descriptive reference values and equations were derived from the data. Results The authors present grip-strength reference values using summary statistics (mean, standard deviation, and percentile). The mean grip strength ranged from 49.7 kg for the dominant hand of men 25 to 29 years of age to 18.7 kg for the nondominant hand of women 75 to 79 years of age. The researchers also present reference regression equations for the dominant and nondominant sides of men and women. The explanatory variables in the equations are age, height, and weight. Conclusion The normative reference values and equations provided in this study may serve as a guide for interpreting grip strength measurements obtained from tested individuals. J Orthop Sports Phys Ther 2018;48(9):685-693. Epub 23 May 2018. doi:10.2519/jospt.2018.7851. PMID- 29792108 TI - Does maximalist footwear lower impact loading during level ground and downhill running? AB - A new model of running shoes which features an extreme cushioning and an oversized midsole, known as the maximalist (MAX) was launched. This design claims to provide excellent shock absorption, particularly during downhill running. This study sought to assess the effects of MAX on the external impact loading, footstrike pattern, and stride length during level ground and downhill running on an instrumented treadmill. Twenty-seven distance runners completed four 5-minute running trials in the two footwear conditions (MAX and traditional running shoes (TRS)) on a level surface (0%) and downhill (10%-declination). Average and instantaneous loading rates (ILRs), footstrike pattern and stride length were measured during the last minute of each running trial. A 12% greater ILR was observed in downhill running with MAX (p = .045; Cohen's d = 0.44) as compared to TRS. No significant difference was found in the loading rates (p > .589) and stride length (p = .924) when running on a level surface. Majority of runners maintained the same footstrike pattern in both footwear conditions. Findings of this study suggested that MAX might not reduce the external impact loading in runners during level and downhill treadmill running. Instead, this type of footwear may conceivably increase the external impact loading during downhill treadmill running. PMID- 29792109 TI - Computational functional genomics-based approaches in analgesic drug discovery and repurposing. AB - Persistent pain is a major healthcare problem affecting a fifth of adults worldwide with still limited treatment options. The search for new analgesics increasingly includes the novel research area of functional genomics, which combines data derived from various processes related to DNA sequence, gene expression or protein function and uses advanced methods of data mining and knowledge discovery with the goal of understanding the relationship between the genome and the phenotype. Its use in drug discovery and repurposing for analgesic indications has so far been performed using knowledge discovery in gene function and drug target-related databases; next-generation sequencing; and functional proteomics-based approaches. Here, we discuss recent efforts in functional genomics-based approaches to analgesic drug discovery and repurposing and highlight the potential of computational functional genomics in this field including a demonstration of the workflow using a novel R library 'dbtORA'. PMID- 29792110 TI - A comparative study of anterior cruciate ligament reconstruction with double, single, or selective bundle techniques. AB - PURPOSE: Reconstruction of the anterior cruciate ligament (ACL) is the most frequently performed reconstructive surgery in the knee. Biomechanical studies have shown that double bundle (DB) reconstruction is better than single bundle (SB) reconstruction with regard to rotational stability. It is postulated that resection of ACL fibres that remain in continuity may be counterproductive for the knee as these fibres have the capacity to produce collagen. In this study, we aimed to evaluate the efficacy among selective bundle, DB and SB ACL reconstructions over a 2-year post-operative follow-up period. METHODS: A retrospective comparative study was conducted for comparison between selective bundle, DB and SB reconstructions. Between 2012 and 2014, 291 ACL reconstructions were performed. Of these, 68 patients had selective ACL reconstructions (group SLB), 147 had DB ACL reconstructions (group DB) and 76 had SB ACL reconstructions (group SB). Institutional Review Board approval was obtained, and all patients provided informed consent. Clinical results were assessed with the International Knee Documentation Committee (IKDC), Lysholm and Tegner scores. Stability was measured using Lachman, pivot shift and anterior drawer stress tests using the KT1000 at 30 degrees of knee flexion. RESULTS: There was no significant difference in ligament grade, function grade, IKDC grade, as well as Tegner and Lysholm means among all three groups after a 2-year follow-up period. CONCLUSION: Selective bundle reconstruction provides comparable results to DB and SB reconstruction techniques. It is a viable alternative for patients with partial tears. PMID- 29792111 TI - Improving hemolysis levels associated with cardiotomy suction. AB - BACKGROUND:: The major source of hemolysis during cardiopulmonary bypass (CPB) remains the cardiotomy suction.1 Previous research has shown that the combination of negative pressures and the massive air-blood interface exponentially increases hemolysis in suctioned blood. OBJECTIVE:: This research aims to decrease hemolysis by eliminating the air-to-blood interface by implementing the Venturi effect to create powerful suction. This research effort hypothesizes that the Venturi suction will result in less hemolysis, indicated by lower plasma free hemoglobin levels (PFH) compared to current vacuum suction. METHOD:: The research hypothesizes that a paradigm approach to cardiotomy suction that utilizes the Venturi effect with shorter tubing lengths and weighted sucker tips will further reduce hemolysis. RESULTS:: The vacuum-suctioned blood showed PFH levels significantly increased from baseline levels (p=0.0039). Neither the Venturi nor paradigm groups showed PFH levels significantly increased from baseline levels (p=0.0625 and p=0.125, respectively). There was a significant difference in PFH levels among the three conditions (p<0.0001). The vacuum condition showed significantly higher levels of PFH compared to both the Venturi and the paradigm conditions (p<0.001 for both). There was no significant difference in the PFH levels between the Venturi and the paradigm groups (p=1.00). CONCLUSION:: This study concludes that vacuum suction causes excessive hemolysis. A Venturi-powered suction system does not cause hemolysis and can be employed to reduce the damaging effects of vacuum suction on blood. PMID- 29792112 TI - Analytical and computational study of an individual-based network model for the spread of heavy drinking. AB - Two simple models for the spread of heavy drinking among a network of individuals are re-introduced and analysed. We provide theorems on the spread of alcohol abuse for these models in cases involving simple connection schemes. Indicators for this spread that resemble the [Formula: see text] used in disease assessment are suggested and studied. We further provide computations with our models on general application networks and begin to study the reliability of the spread indicators. PMID- 29792113 TI - The influence of hold regularity on perceptual-motor behaviour in indoor climbing. AB - Climbers often train on indoor climbing walls, which are modifiable to simulate features of outdoor climbing environments at different levels of difficulty. The aim of this study was to evaluate the influence of regularity of climbing holds on emergent perceptual-motor behaviours. Skilled climbers performed six repetitions of two topographically similar routes on an indoor climbing wall. One route was composed of 18 different types of hand holds (irregular route), whereas the other route had only two types of hand holds (regular route). Preview and climbing durations, as well as visual search behaviours, were recorded. Participants rated the regular route as more difficult to climb, requiring greater perceived effort to complete. The time spent previewing, and then climbing the routes, was reduced on average by 12% and 16%, respectively in the irregular route compared to the regular route. There were more fixations made when climbing the regular route (281 vs. 222 fixations per trial). It seems the climbers were more careful and thorough in their gaze behaviours with the regular route because of the additional technical demands it presented, whereas the irregular route afforded a more superficial visual exploration with use of more frequent saccades between holds. The findings suggest how irregularity in the environment is exploited by skilled climbers, apparently making the practice context easier to perceive and act in. PMID- 29792114 TI - Innovating urinary catheter design: An introduction to the engineering challenge. AB - Every day, people around the world rely on intermittent and indwelling urinary catheters to manage bladder dysfunction, but the potential or actual harm caused by these devices is well-recognised. Current catheter designs can cause urinary tract infection and septicaemia, bladder and urethral trauma and indwelling devices frequently become blocked. Furthermore, the devices can severely disrupt users' lives, limiting their daily activities and can be costly to manage for healthcare providers. Despite this, little significant design innovation has taken place in the last 80 years. In this article current catheter designs and their limitations are reviewed, common catheter-associated problems are outlined and areas of design ripe for improvement proposed. The potential to relieve the individual and economic burden of catheter use is high. PMID- 29792115 TI - Using Machine Learning to Advance Personality Assessment and Theory. AB - Machine learning has led to important advances in society. One of the most exciting applications of machine learning in psychological science has been the development of assessment tools that can powerfully predict human behavior and personality traits. Thus far, machine learning approaches to personality assessment have focused on the associations between social media and other digital records with established personality measures. The goal of this article is to expand the potential of machine learning approaches to personality assessment by embedding it in a more comprehensive construct validation framework. We review recent applications of machine learning to personality assessment, place machine learning research in the broader context of fundamental principles of construct validation, and provide recommendations for how to use machine learning to advance our understanding of personality. PMID- 29792116 TI - The epistemic culture in an online citizen science project: Programs, antiprograms and epistemic subjects. AB - In the past decade, some areas of science have begun turning to masses of online volunteers through open calls for generating and classifying very large sets of data. The purpose of this study is to investigate the epistemic culture of a large-scale online citizen science project, the Galaxy Zoo, that turns to volunteers for the classification of images of galaxies. For this task, we chose to apply the concepts of programs and antiprograms to examine the 'essential tensions' that arise in relation to the mobilizing values of a citizen science project and the epistemic subjects and cultures that are enacted by its volunteers. Our premise is that these tensions reveal central features of the epistemic subjects and distributed cognition of epistemic cultures in these large scale citizen science projects. PMID- 29792117 TI - The Rockwood classification in acute acromioclavicular joint injury does not correlate with symptoms. AB - PURPOSE: Rockwood classified acromioclavicular (AC) joint injuries by displacement of the joint on radiographs. This classification has driven the management dogma of acute AC dislocation. The correlation between Rockwood grade and symptoms has not been described in acute injury. This study assesses that relationship. METHODS: This series included 77 patients with acute AC joint injury (<6 weeks), treated between 2006 and 2015. Objective and patient-reported measures enabled correlation between clinical measures and Rockwood grade. RESULTS: The mean age was 32 years (+/-11.86; range 17-59 years); 88% were male. Forty-four per cent were professional athletes and 43% suffered injury during rugby. The mean time from injury to presentation was 2 weeks (+/-1.64; range 0-5 weeks). There was poor correlation between Rockwood classification and pain (visual analogue scale) ( rs = 0.05; p = 0.752). Poor correlation was noted between Rockwood grade and functional deficit (elevation ( rs = 0.18; p = 0.275), abduction ( rs = 0.19; p = 0.246) and strength ( rs = 0.09; p = 0.579) vs. contralateral side). Oxford and Constant scores did not correlate with Rockwood grade ( rs = 0.13; p = 0.972 and 0.01; p = 0.448, respectively). CONCLUSION: The Rockwood grade does not correlate with clinical symptoms in acute AC joint injury. Previous evidence demonstrates the Rockwood classification's limitations in predicting the structures injured. Therefore, the reliability of using the Rockwood grade as a decision-making tool in the management of acute AC joint dislocation is unclear. PMID- 29792118 TI - Extracorporeal membrane oxygenation support in individuals with thoracic insufficiency. AB - INTRODUCTION:: Respiratory failure is the leading cause of mortality in individuals with congenital spine and rib deformities. We present a case report of a child with Jeune syndrome surviving respiratory failure using extracorporeal membrane oxygenation (ECMO). We also summarize thoracic insufficiency syndrome cases reported in the Extracorporeal Life Support Organization (ELSO) registry. CASE REPORT:: A two-year-old male with a chest circumference less than a third percentile for age was admitted with influenza pneumonia developing a peak oxygenation index of 103.5. The child survived to baseline pulmonary function after nine days of venous-arterial ECMO support. DISCUSSION:: The ELSO registry contained 27 individuals with a surrogate diagnosis of thoracic insufficiency (0.05%). There was no significant difference in survival to discharge for thoracic insufficiency patients (52%) compared to a previously healthy population supported with ECMO. CONCLUSION:: ECMO is safe and may be effective in supporting individuals with thoracic insufficiency. PMID- 29792119 TI - MAPLE 2.3.0: an improved system for evaluating the functionomes of genomes and metagenomes. AB - MAPLE is an automated system for inferring the potential comprehensive functions harbored by genomes and metagenomes. To reduce runtime in MAPLE analyzing the massive amino acid datasets of over 1 million sequences, we improved it by adapting the KEGG automatic annotation server to use GHOSTX and verified no substantial difference in the MAPLE results between the original and new implementations. PMID- 29792121 TI - ABCG2 Polymorphism rs2231142 and hypothyroidism in metastatic renal cell carcinoma patients treated with sunitinib. AB - Background and aim Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics. Patients and methods We included 79 mRCC patients who started sunitinib between November 2005 and March 2016. Serum thyroid function markers were collected at start and during sunitinib therapy. Germ-line DNA genotyping for 16 SNPs in 8 candidate genes was performed. Endpoints were time to increase in thyroid stimulating hormone (TSH) and time to decrease in T4 or free T4 (FT4) on day 1 and day 28 of each sunitinib cycle. Results Patients with the ABCG2 rs2231142 CC-genotype had a significantly longer time-to-TSH-increase on day 1 (11 vs. 5 cycles; p = 0.0011), and time-to-T4/FT4-decrease on day 1 (not reached vs. 10 cycles; p = 0.013) and day 28 (28 vs. 7 cycles; p = 0.03) compared to CA-carriers. Patients with the CYP3A5 rs776746 GG-genotype had a significantly longer time-to-TSH-increase at day 1 compared to GA-patients: 11 vs. 5 cycles (p = 0.0071). Significant associations were also found between PDGFRA rs35597368 and rs1800812 and time-to-TSH-increase at day 28. Conclusion Polymorphism rs2231142 in the efflux pump ABCG2 is associated with hypothyroidism in mRCC patients treated with sunitinib. PMID- 29792122 TI - Drug cost avoidance in clinical trials of breast cancer. AB - Background The objectives of this study were to determine if clinical trials in breast cancer, with an investigational drug, created direct drug cost savings for the healthcare system related to cost avoidance of the best standard of care treatments used in these studies. The aim was to quantify this potential drug cost avoidance. Methods We conducted a retrospective observational study of the drug cost avoidance during the study period (2014-2016). We included clinical trials with investigational drug, managed by pharmacy department and provided by the sponsor. The patients included had a therapeutic alternative defined as standard treatment that should have been received in case of not participating in the clinical trial. Direct cost savings, to national healthcare system, associated to clinical trials were calculated. Results Thirty-seven clinical trials with a total of 89 breast cancer patients were included in the study. A total of 62.2% were phase III and 75.7% belonged to the pharmaceutical industry. They provided a total cost avoidance of 957,246? (1,130,028$), an average cost avoidance per patient of 10,756? (12,697$). Conclusions Our study suggests that those clinical trials in which investigational drug are provided or refunded by the sponsor provide substantial cost savings. Due to the shortage of published articles that calculate the cost avoided in medication, we cannot compare directly the results obtained in the different institutions. PMID- 29792123 TI - User acceptance of an app-based adherence intervention: Perspectives from patients taking oral anticancer medications. AB - Background Widespread adoption by patients is imperative for the success of app based interventions for enhancing adherence to oral anticancer medications. Patients' attitudes and beliefs should be evaluated to understand determinants of their acceptance and adoption of such interventions. Objective To identify factors that influence cancer patients' intention to adopt an app-based system for enhancing oral anticancer medication adherence. Methods This study was conducted as part of the usability evaluation of an app-based system for enhancing adherence. We followed the grounded theory approach employing audio recorded face-to-face interviews for data collection from patients taking oral anticancer medications (n = 15) and caregivers of such patients (n = 3). Data analysis involved verbatim transcription of all interviews, coding of the transcripts and field notes, detailed memo writing, and constant comparative evaluation of emergent categories. Results A conceptual framework of facilitating and hindering factors for users' adoption intention for an oral anticancer medication adherence app was developed. Findings suggest that facing difficulties in maintaining adherence and patients' perceived superiority of the app over their current methods facilitate adoption intention. In contrast, having to pay, lack of language options and users' perception of low competence in using an app were the hindrance factors. Conclusion This study showed that adoption of adherence apps could be explained by technology acceptance constructs, such as performance expectancy. Adoption intention was also facilitated by patients perceived vulnerabilities in maintaining adherence to their medications, which was a health behaviour construct. Implementation of app-based programs should address patients' perceived vulnerabilities and relative advantage of the app over their current methods. Clinicians and app developers should also consider the financial, technological and language barriers for end users. PMID- 29792124 TI - Hypersensitivity to alemtuzumab. A safe and effective desensitization protocol: A case report. AB - We describe a successful desensitization to alemtuzumab in one patient diagnosed with T-cell prolymphocytic leukaemia. Alemtuzumab treatment was initiated during infusion number 18, the patient showed cutaneous eruption with a miliary pattern, despite premedication with corticosteroids and antihistamines. The eruption returned with successive alemtuzumab infusions (infusions 19, 20 and 21), remained present for longer and was more severe with each infusion. The patient was referred to our Allergy Unit as it was necessary to maintain alemtuzumab treatment. Total immunoglobulin E level was 3 UI/ml and specific immunoglobulin E against more common pneumo-allergens, food, latex and hamster were inferior to 0.35 UI/ml. Prick test using the undiluted drug (30 mg/ml) and intradermal tests using serial dilutions (1/10, 1/100) were performed. The result of alemtuzumab skin prick test was 4 mm. The intradermal skin test result was positive at 1/100 dilution (papule: 8 mm; erythema: 12 mm). The basophil activation test with alemtuzumab was performed concluding that 10% of the basophils were activated by alemtuzumab. The patient underwent alemtuzumab desensitization according to a 12 step protocol that resolved to be safe and efficacious. Our experience may be helpful for similar clinical cases where the therapeutic options are very limited and a life-threatening condition such T-cell prolymphocytic leukaemia is present. In addition, a careful risk/benefit ratio should be considered and accurate informed consent is mandatory. PMID- 29792125 TI - Characteristics of Apixaban-Treated Patients, Evaluation of the Dose Prescribed, and the Persistence of Treatment: A Cohort Study in Catalonia. AB - BACKGROUND: Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. OBJECTIVES: (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients. METHODS: Cohort study using data from primary care (System for Research in Primary Care database, users of the Institut Catala de la Salut; Catalonia, Spain) from August 2013 to December 2015. RESULTS: Mean age for apixaban-treated patients was 71.8 years (standard deviation = 11.1) and 55.6% were male. In all, 3.2% of patients receiving apixaban were taking drugs described as potentially related to either pharmacokinetic or pharmacodynamic interactions. According to the summary of product characteristics, 81.1% of patients with a recommended dose of 2.5 mg twice daily and 51.8% with a recommended dose of 5 mg twice daily actually took this dose. After 1 year of follow-up, 62.6% of the apixaban users showed good adherence. CONCLUSION: The prescribed dose of apixaban did not fully follow the recommended dose, particularly in patients who were treatment naive. Patients with a prior history of anticoagulant treatment were more likely to remain persistent to treatment with apixaban. PMID- 29792126 TI - Neuropathological profile of the pentylenetetrazol (PTZ) kindling model. AB - INTRODUCTION: There are three phases of seizure developing in pentylenetetrazol (PTZ)-induced kindling animal model: (i) pre-kindling phase; (ii) kindling phase or after animals are fully kindled; (iii) post-kindling phase with non-provoked spontaneous recurrent seizures. The aims of this review were to summarize the progress over time of the electroencephalographic features and neuropathological alterations in kindled PTZ treated animals. MATERIALS AND METHODS: Keywords relevant to PTZ kindling were used to a guide a literature search on Pubmed, Medline and Cochrane Library. RESULTS: Clonic seizures induced PTZ at kindling phase led to a strong c-Fos expression in the hippocampus. Although, decline hippocampal neuron and metabolism disturbances were detected at pre-kindlig phase. Repeated PTZ induced seizures alter the GABA-mediated inhibition and glutamate-mediated excitation, which may contribute to increased seizure susceptibility. Similar to chemical animal models such as the pilocarpine and the kainic acid models, mossy fiber sprouting, hippocampal damage, and glucose hypometabolism had been seen after PTZ induced seizures. CONCLUSION: PTZ kindling model may improve understanding of the seizures development provided that the differences existing between the phases of kindling model are taken into account. PMID- 29792127 TI - Listeria monocytogenes infection enhances the interaction between rat non classical MHC-Ib molecule and Ly49 receptors. AB - Murine NK cell Ly49 receptors, functionally analogous to KIRs in humans recognize MHC class I molecules and play a key role in controlling NK cell function. We have previously shown that the paired activating Ly49s4 and inhibitory Ly49i4 receptors recognize undefined non-classical MHC-Ib ligands from the RT1-CE region in rats. Here, the RT1-CE16 gene of the RT1d haplotype was stably transfected into the mouse RAW macrophage cell line, termed RAW-CE16d cells. Combining RAW CE16d cells with Ly49 expressing reporter cells demonstrated Ly49i4 and Ly49s4 specificity for CE16d. The Ly49s4/i4:CE16d interaction was confirmed by specific MHC-I blocking monoclonal Abs. Further, we used our in vitro model to study the effect of Listeria monocytogenes (LM) on CE16d after infection. LM infection and IFN-gamma stimulation both led to enhanced CE16d expression on the surface of transfected RAW-CE16d cells. Interestingly, the reporter cells displayed increased response to LM-infected RAW-CE16d cells compared with IFN-gamma-treated RAW-CE16d cells, suggesting a fundamental difference between these stimuli in supporting enhanced Ly49 recognition of CE16d. Collectively, our data show that Ly49s4 and Ly49i4 recognize the non-classical RT1-CE16d molecule, which in turn is up-regulated during LM infection and thereby may contribute to NK-mediated responses against infected cells. PMID- 29792129 TI - Exploring Intimate Partner Violence Before, During, and After Pregnancy in Bangladesh. AB - Intimate partner violence (IPV) against pregnant or postpartum women is known to have multiple detrimental effects on women and their children. Although results from past research suggest much continuity in trajectories of IPV, it is unclear whether pregnancy interrupts or augments these patterns. Little is known about how physical, sexual, and psychological IPV change and overlap throughout a woman's transition to parenthood. Relying on population-based data, this study examines the prevalence, co-occurring nature, and the changing patterns of physical, sexual, and psychological IPV before, during, and after pregnancy in Bangladesh. Cross-sectional survey data were collected between October 2015 and January 2016 in the Chandpur District of Bangladesh from 426 new mothers, aged 15 to 49 years, who were in the first 6 months postpartum. IPV was assessed with a validated set of survey items. The frequencies of different types of IPV victimization according to the period of occurrence were calculated separately and in a cumulative, co-occurring manner. The prevalence of physical IPV before, during, and after pregnancy was 52.8%, 35.2%, and 32.2%, respectively. The comparative figures for psychological IPV were 67.4%, 65%, and 60.8%, and for sexual IPV were 21.1%, 18.5%, and 15.5%, respectively. The results demonstrate a notable continuity in IPV victimization before, during, and after pregnancy. Psychological IPV is the only type to exhibit a significant reduction during and after pregnancy, compared with before pregnancy, but it commonly overlaps with physical IPV, which shows a significant change during pregnancy and little change in the postpartum period. At the same time, pregnancy and childbirth offer little protection against IPV for women in relationships characterized by psychological or sexual victimization, both of which commonly overlap with physical IPV. Results reinforce the need to conduct routine screening during pregnancy to identify women with a history of IPV and to offer necessary help and support. PMID- 29792130 TI - Weekday-weekend variations in mother-/father-child physical activity and screen time relationship: A cross-sectional study in a random sample of Czech families with 5- to 12-year-old children. AB - This study assessed the associations between these factors in a random sample of Czech families with preschool and school-aged children. A nationally representative sample comprised 185 families with preschool children and 649 families with school-aged children (dyads; both parents and child n = 365, mother and child n = 730, and father and child n = 469). The participants wore Yamax Digiwalker SW-200 pedometers at least four weekdays and both weekend days and completed family logbooks (anthropometric parameters, daily step counts (SC), and screen time (ST)). When a parent (fathers at weekends and mothers both on weekdays and at weekends) achieved 10,000 SC per day, their children were also significantly (OR = 2.93-6.06, 95% CI = 2.02-9.26) more likely to meet the daily SC recommendation. On the contrary, the involvement of fathers in organized leisure-time PA reduced their children's odds of meeting the SC recommendation on weekdays (OR = 0.53, 95% CI = 0.31-0.89) and at weekends (OR = 0.41, 95% CI = 0.24-0.72). The excessive ST of parents at weekends reduced the odds of their children meeting the SC recommendation (mother-child dyads: OR = 0.44, 95% CI = 0.26-0.72; father-child dyads: OR = 0.63, 95% CI = 0.37-1.06). High levels of parents' PA contribute to the achievement of the recommended daily PA in children on weekdays and at weekends. Excessive weekend ST of parents reduces their odds of their children achieving the recommended daily PA; however, the influence of parents' PA on their children's achieving the recommended daily PA is stronger than the inhibitory effect of ST. PMID- 29792131 TI - Management of Nursing Workplace Incivility in the Health Care Settings: A Systematic Review. AB - Workplace incivility is a well-documented issue in nursing in the health care setting. It has the potential to cause emotional and physical distress in victims and potentially affects the quality of care provided. The purpose of this study was to critique and summarize the most recent, available evidence related to interventions in assisting nursing staff working in health care settings in managing incivility. This systematic review of literature yielded 10 studies meeting the criteria. The studies were mostly identified as lower quality research. Despite the lower quality of research, the collection of evidence suggests the use of a combination of educational training about workplace incivility, training about effective responses to uncivil workplace behaviors, and active learning activities to practice newly learned communication skills, in assisting nurses in improving their ability to manage incivility in the workplace. PMID- 29792132 TI - Relationships of Musculoskeletal Symptoms, Sociodemographics, and Body Mass Index With Leisure-Time Physical Activity Among Nurses. AB - Nurses have a high prevalence of musculoskeletal symptoms from patient handling tasks such as lifting, transferring, and repositioning. Comorbidities such as musculoskeletal symptoms may negatively affect engagement in leisure-time physical activity (LTPA). However, limited data are available on the relationship between musculoskeletal symptoms and LTPA among nurses. The purpose of this study was to describe musculoskeletal symptoms and LTPA, and to examine the relationships of musculoskeletal symptoms, sociodemographics, and body mass index with LTPA among nurses. Cross-sectional data on sociodemographics, employment characteristics, musculoskeletal symptoms, body mass index, and LTPA were collected from a statewide random sample of 454 California nurses from January to July 2013. Descriptive statistics, bivariate and multiple logistic regressions were performed. We observed that non-White nurses were less likely to engage in regular aerobic physical activity than White nurses (odds ratio [OR] = 0.61; 95% confidence interval [CI] = [0.40, 0.94]). Currently working nurses were less likely to engage in regular aerobic physical activity than their counterparts (OR = 0.48; 95% CI = [0.25, 0.91]). Nurses with higher body mass index were less likely to perform regular aerobic physical activity (OR = 0.93; 95% CI = [0.89, 0.97]) or muscle-strengthening physical activity (OR = 0.92; 95% CI = [0.88, 0.96]). This study found no evidence that musculoskeletal symptoms may interfere with regular engagement in LTPA. Physical activity promotion interventions should address employment-related barriers, and particularly target racial minority nurses and those who have a high body mass index. PMID- 29792133 TI - Impact of Collaborative Shared Medical Appointments on Diabetes Outcomes in a Family Medicine Clinic. AB - Purpose The purpose of this study is to evaluate the impact of a collaborative diabetes shared medical appointment on patient outcomes in an urban family medicine practice. Methods Fifty-nine patients were enrolled to participate in multiple shared medical appointments (SMAs) over 12 months. Baseline data included hemoglobin (A1C), lipids, systolic blood pressure (SBP), weight, adherence to American Diabetes Association (ADA) guidelines, and surveys, including the Problem Areas in Diabetes (PAID-2) scale and the Spoken Knowledge in Low Literacy in Diabetes Scale (SKILLD). A1C and SBP were evaluated at each visit. Lipid control was assessed at baseline and at 6 and 12 months. Adherence to ADA guidelines, SKILLD and PAID-2 survey scores, and number of antihyperglycemic and antihypertensive medications were also evaluated at 12 months. Results Thirty-eight patients completed the study. Compared with baseline, A1C and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly over 12 months ( P < .001 and P = .004, respectively). More patients became compliant with the ADA guidelines throughout the course of the study. Specifically, more patients achieved the LDL-C goal of <=100 mg/dL (2.59 mmol/L; P < .001), were prescribed appropriate antihypertensive medications ( P < .001) and aspirin ( P < .001), and received the pneumonia vaccine ( P < .001). PAID-2 and SKILLD survey scores also significantly improved over the course of the study ( P <= .001 and P = .003, respectively). Conclusion Short-term interdisciplinary SMAs decreased A1C and LDL-C, improved patient adherence to ADA guidelines, improved emotional distress related to diabetes, and increased knowledge of diabetes. PMID- 29792134 TI - Editorial: Advances in Psychopharmacological Treatment. PMID- 29792135 TI - Modified LDL immune complexes and cardiovascular disease. AB - Modified forms of LDL, both spontaneously formed in the organism or prepared in the laboratory, are immunogenic. As a consequence, antigen-antibody complexes (immune complexes, IC) formed in vivo can be measured in the peripheral blood, and their levels are strong predictors of cardiovascular disease (CVD). It has been possible to generate antibodies that recognize different LDL modifications, allowing the analysis of circulating IC constitution. Clinical studies showed that the antigenic constitution of the IC has a modulating effect on the development of CVD. Patients whose IC react strongly with antibodies to copper oxidized LDL (oxLDL) show progressive development of atherosclerosis as shown by increased intima-media thickness and increased coronary calcification scores. In contrast, patients whose IC react strongly with antibodies to the heavily oxidized malondialdehyde LDL prepared in vitro (MDA-LDL) are at a high risk of acute vascular events, mainly myocardial infarction. In vitro studies have shown that while oxLDL IC induce both cell proliferation and mild to moderate macrophage apoptosis, MDA-LDL IC induce a more marked macrophage apoptosis but not cell proliferation. In addition, MDA-LDL IC induce the release of higher levels of matrix metalloproteinases and TNF than oxLDL IC. High levels of TNF are likely to be a major factor leading to apoptosis and high levels of metalloproteinases are likely to play a role in the thinning of the fibrous cap of the atheromatous plaque. The combination of apoptosis and fibrous cap thinning are well-known characteristics of vulnerable plaques, which are more prone to rupture and responsible for the majority of acute cardiovascular events. PMID- 29792136 TI - SGLT-2 inhibitors in diabetic kidney disease: what lies behind their renoprotective properties? AB - BACKGROUND: Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD. METHODS: A systematic literature search of bibliographic databases to identify preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on DKD. RESULTS: Preclinical studies performed in animal models of DKD support the renoprotective action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly supported by human studies showing that these agents prevent the progression of albuminuria and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors is not fully explained by their glucose lowering properties. Attenuation of glomerular hyperfiltration and improvement in a number of surrogate risk factors, including associated reduction in systemic blood pressure, body weight, and serum uric acid levels may represent plausible mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors. Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway with protective activities. CONCLUSION: SGLT-2 inhibition emerges as a novel therapeutic approach of type 2 diabetes with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are clearly warranted to elucidate this favorable effect in patients with overt DKD. PMID- 29792137 TI - Recent Trends in Nanocrystals for Pharmaceutical Applications. AB - BACKGROUND: As the quick development of modern methods and technologies currently, more and more drugs have been invented with a better efficiency. However, the poor water solubility has limited the drugs' pharmaceutical application. METHODS: Tremendous research has been put in the design and development of nanocrystals for pharmaceutical applications over the past few decades. The nanocrystals not only have the chance to solve the poor solubility problem, but also could conquer the bioavailability and even the specific delivery problems. The physical properties of drugs can be changed dramatically due to the change of their size in a nanodimension. Therefore, the nanocrystals have great potential to overcome the challenge to design and development of new drugs for pharmaceutical applications. RESULTS: In this review, we provide an overview of the recent trends in nanocrystals for pharmaceutical applications. CONCLUSION: The current technologies including top-down, bottom-up, and combinative technologies for nanocrystals were fully examined. Most importantly, the emphasis is put on the pharmaceutical applications including their formulation, administration methods, safety, and toxicity. The commercial status, limitations, challenges, and future trends of the nanocrystals for pharmaceutical applications were also discussed. PMID- 29792138 TI - Therapeutic Potential of Phytomedicines and Novel Polymeric Strategies for Significant Management of Candidiasis. AB - BACKGROUND: Candidiasis is one of the most common opportunistic fungal infections caused by genus Candida. The genus is composed of around 200 species. The most virulent among all are, Candida albicans followed by various nonalbicans species. Despite various treatments available, the incidence of severe systemic fungal infections is increasing, and with it the related morbidity and mortality, in relation to the misuse of antimicrobials and the emergence of drug-resistant fungal species. Therefore, various novel therapeutic approaches need to be developed and explored to overcome these limitations and effective management of candidiasis. OBJECTIVE: In this review, we focused on natural herbal remedies and significance of novel formulation approaches for the treatment of candidiasis. CONCLUSION: The reported studies suggested the promising role of phytomedicines and novel polymeric drug delivery systems in therapeutic management of candidiasis. Phytomedicines are effective substitutes of synthetic drugs as they are inexpensive with lesser number of side effects. Various novel particulate approaches can be successfully used to reduce fungal burden at the target site. PMID- 29792139 TI - Process Intensification Techniques for the Production of Nano- and Submicronic Particles for Food and Medical Applications. AB - BACKGROUND: Nowadays, nanoparticles are of great interest for the industry due to their numerous possible applications in several fields. Research on this topic seeks to develop many procedures to produce nanoparticles, mostly at lab scale, batch-wise and with low yield. These procedures generally do not suit industrial needs of continuous, high capacity production. Moreover, the product characteristics require targeting narrow particle size distributions and high quality, which is difficult to achieve by traditional equipment. METHODS: Process intensification techniques aim to minimize plant size of continuous, high yield equipment capable to produce specific sized, high quality nanoparticles, combined with an increase in energy efficiency, safety and cost reduction. DISCUSSION: This paper reviews some adopted Process Intensification (PI) techniques for nanoparticles synthesis processes employed in the food and pharmaceutical sector. CONCLUSION: By reducing the technology transfer gap, nanotechnologies may become convenient and feasible, allowing both industries to achieve the production of higher quality products with particular characteristics without sensibly increasing additional costs. This will represent in the next future a strategic key feature of industries in the global market. PMID- 29792140 TI - A Convenient Method for the Synthesis of Chromeno[4,3-b]pyridines Via Three component Reaction. AB - AIM AND OBJECTIVE: The importance of Chromeno[4,3-b]pyridines in bioactive compounds, highlighted the ongoing research on developing novel methods for the construction of this heterocyclic scaffold. Regarding the advantageous features of multi-component reactions in organic synthesis, we will try to synthesize pyridocoumarins through this method. MATERIALS AND METHODS: Chromeno[4,3 b]pyridines were conveniently prepared from a threecomponent condensation reaction between 4-hydroxy coumarin, ammonia and ethyl 2,4-dioxo-4- arylbutanoates in refluxing n-propanol. The synthesized compounds were characterized by NMR, IR and Mass spectroscopy. RESULTS: The reaction proceeded through an in situ formed 4-amino coumarin, affording eight new target compounds in good yields. CONCLUSION: This method introduce a novel approach to ethyl 4 aryl-5-oxo-5H-chromeno[4,3- b]pyridine-2-carboxylate derivatives and allow organic chemists to prepare 4-aminocoumarin in reaction medium. PMID- 29792141 TI - Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions. AB - AIM AND OBJECTIVE: Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available. MATERIALS AND METHODS: We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs. RESULTS: These models obtain an overall area under the receiver operating characteristic curve (AUROC) of 0.843 and an overall area under the precision-recall curve (AUPR) of 0.395, outperforming seven structural fingerprint-based prediction models. Using the method, we predicted skin striae for fluticasone propionate, dermatitis acneiform for mometasone, and decreased libido for irinotecan, as demonstrations. Furthermore, we analyzed the top binding proteins associated with some of the ADRs, which can help to understand and/or generate hypotheses for underlying mechanisms of ADRs. CONCLUSION: Machine learning combined with molecular docking can help to predict ADRs for drug molecules and provide possible explanations for the ADR mechanisms. PMID- 29792143 TI - Recent Updates on Novel Approaches in Insulin Drug Delivery: A Review of Challenges and Pharmaceutical Implications. AB - Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic beta-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major research is ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance the pharmaceutical performance of the insulin therapy. Despite facing substantial challenges in developing efficient delivery systems for insulin, vast research studies have been carried out for the development of smart delivery systems to deliver insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market. PMID- 29792144 TI - Biomedical Applications of Aromatic Azo Compounds. AB - Azo dyes are widely used in textile, fiber, cosmetic, leather, paint and printing industries. Besides their characteristic coloring function, azo compounds are reported as antibacterial, antiviral, antifungal and cytotoxic agents. They have the ability to be used as drug carriers, either by acting as a 'cargo' that entrap therapeutic agents or by prodrug approach. The drug is released by internal or external stimuli in the region of interest, as observed in colon targeted drug delivery. Besides drug-like and drug carrier properties, a number of azo dyes are used in cellular staining to visualize cellular components and metabolic processes. However, the biological significance of azo compounds, especially in cancer chemotherapy, is still in its infancy. This may be linked to early findings that declared azo compounds as one of the possible causes of cancer and mutagenesis. Currently, researchers are screening the aromatic azo compounds for their potential biomedical use, including cancer diagnosis and therapy. In this review, we highlight the medical applications of azo compounds, particularly related to cancer research. The biomedical significance of cis-trans interchange and negative implications of azo compounds are also discussed in brief. PMID- 29792142 TI - Collaboration of the Joint Research Centre and European Customs Laboratories for the Identification of New Psychoactive Substances. AB - BACKGROUND: The emergence of psychoactive designer drugs has significantly increased over the last few years. Customs officials are responsible for the control of products entering the European Union (EU) market. This control applies to chemicals in general, pharmaceutical products and medicines. Numerous products imported from non-EU countries, often declared as 'bath salts' or 'fertilizers', contain new psychoactive substance (NPS). REVIEW: These are not necessarily controlled under international law, but may be subject to monitoring in agreement with EU legislation. This situation imposes substantial challenges, for example, for the maintenance of spectral libraries used for their detection by designated laboratories. The chemical identification of new substances, with the use of powerful instrumentation, and the time needed for detailed analysis and interpretation of the results, demands considerable commitment. The EU Joint Research Centre endeavors to provide scientific support to EU Customs laboratories to facilitate rapid identification and characterisation of seized samples. In addition to analysing known NPS, several new chemical entities have also been identified. Frequently, these belong to NPS classes already notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) by the European Early- Warning System (EWS). CONCLUSION: The aim of this paper is to discuss the implementation of workflow mechanisms that are in place in order to facilitate the monitoring, communication and management of analytical data. The rapid dissemination of this information between control authorities strives to help protect EU citizens against the health risks posed by harmful substances. PMID- 29792145 TI - 1,2,4-Oxadiazole as a Privileged Scaffold for Anti-inflammatory and Analgesic Activities: A Review. AB - 1,2,4-Oxadiazole is one of the important heterocycles used by medicinal chemists in designing a new therapeutic molecule. The compounds containing this nucleus are reported to have a wide range of pharmaceutical and biological applications including anti-inflammatory and analgesic activities. The fused and pendent 1,2,4 oxadiazole moiety has been traced in a number of well established, commercially available drugs. This review article provides an up to date information about techniques adopted for the synthesis of 1,2,4-oxadiazoles, and their therapeutic importance as anti-inflammatory and analgesic agents. PMID- 29792147 TI - Crystal Structure of Mistletoe Lectin I (ML-I) from Viscum album in Complex with 4-N-Furfurylcytosine at 2.85 A Resolution. AB - BACKGROUND: Viscum album (the European mistletoe) is a semi-parasitic plant, which is of high medical interest. It is widely found in Europe, Asia, and North America. It contains at least three distinct lectins (i.e. ML-I, II, and III), varying in molecular mass and specificity. Among them, ML-I is in focus of medical research for various activities, including anti-cancer activities. To understand the molecular basis for such medical applications, a few studies have already addressed the structural and functional analysis of ML-I in complex with ligands. In continuation of these efforts, we are reporting the crystal structure of ML from Viscum album in complex with the nucleic acid oxidation product 4-N furfurylcytosine (FC) refined to 2.85 A resolution. FC is known to be involved in different metabolic pathways related to oxidative stress and DNA modification. METHODS: X-ray suitable hexagonal crystals of the ML-I/FC complex were grown within four days at 294 K using the hanging drop vapor diffusion method. Diffraction data were collected up to a resolution of 2.85 A. The ligand affinity was verified by in-silico docking. RESULTS: The high-resolution structure was refined subsequently to analyze particularly the active site conformation and a binding epitope of 4-N-furfurylcytosine. A distinct 2Fo-Fc electron density at the active site was interpreted as a single FC molecule. The specific binding of FC is achieved also through hydrophobic interactions involving Tyr76A, Tyr115A, Glu165A, and Leu157A of the ML-I A-chain. The binding energy of FC to the active site of ML-I was calculated as well to be -6.03 kcal mol-1. CONCLUSION: In comparison to other reported ML-I complexes, we observed distinct differences in the vicinity of the nucleic acid base binding site upon interaction with FC. Therefore, data obtained will provide new insights in understanding the specificity, inhibition, and cytotoxicity of the ML-I A-chain, and related RIPs. PMID- 29792146 TI - Use of Bipolar Radiofrequency Catheter Ablation in the Treatment of Cardiac Arrhythmias. AB - BACKGROUND: Arrhythmia management is a complex process involving both pharmacological and non-pharmacological approaches. Radiofrequency ablation is the pillar of nonpharmacological arrhythmia treatment. Unipolar ablation is considered to be the gold standard in the treatment of the majority of arrhythmias; however, its efficacy is limited to specific cases. In particular, the creation of deep or transmural lesions to eliminate intramurally originating arrhythmias remains inadequate. Bipolar ablation is proposed as an alternative to overcome unipolar ablation boundaries. RESULTS: Despite promising results gained from in vitro and animal studies showing that bipolar ablation is superior in creating transmural lesions, the use of bipolar ablation in daily clinical practice is limited. Several studies have been published showing that bipolar ablation is effective in the treatment of clinical arrhythmias after failed unipolar ablation, however, there is inconsistency regarding the safety of bipolar ablation within the available research papers. According to research evidence, the most common indications for bipolar ablation use are ventricular originating rhythmic disorders in patients with structural heart disease resistant to standard radiofrequency ablation. CONCLUSION: To allow wider clinical application the efficiency and safety of bipolar ablation need to be verified in future studies. PMID- 29792148 TI - Homopiperazine Derived Female Controlled Vaginal Trichomonacidal Contraceptive: An Addition to Structure-Activity Relationship. AB - BACKGROUND: In our previous work, several piperazine derived bis(dialkylaminethiocarbonyl) disulfides and disulfide esters of dithiocarbamic acid have been synthesized and evaluated for their spermicidal and microbicidal efficacy. These studies have provided some promising compounds for developing a dually active vaginal microbicidal contraceptive which is under pre-clinical stage. OBJECTIVE: The main objective of this study was the design synthesis and biological evaluation of bis(dialkylaminethiocarbonyl) disulfides (4-15) and 2,2' disulfanediylbis (3-(substituted-1-yl) propane-2,1-diyl) disubstituted-1 carbodithioates (19-28) as non-surfactant molecules capable of eliminating Trichomonas vaginalis as well as irreversibly immobilizing 100% human sperm promptly. METHOD: Spermicidal, anti-trichomonas, cytotoxicity and biocompatibility study of the synthesized compounds was done as per the reported methodologies. RESULT: Among bis(dialkylaminethiocarbonyl) disulfides (4-15, Table 1), compound 4 (MEC 0.02 mM) was found to be the most desirable for spermicidal activity as it was 40 times more active than Nonoxynol-9 (N-9), and also active against Trichomonas vaginalis (MIC 0.02 &1.10 mM). 2, 2' disulfanediylbis (3-(substituted- 1-yl) propane-2, 1-diyl) disubstituted-1 carbodithioates (19-28, Table 2), and compounds (19, 22, 23, and 24 MEC 0.05 mM) were sixteen times more active than N-9 with promising Trichomonacidal activity. CONCLUSION: This study suggested that the disulfide linkage alone and dithiocarbamate along with disulfide group within the same chemical entity impart the desired multiple activities of compounds. PMID- 29792150 TI - Synthesis and biological evaluation of novel 2,3-disubstituted benzofuran analogues of GABA as neurotropic agents. AB - BACKGROUND: Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries. OBJECTIVE: To evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. METHODS: The ligands with the best physicochemical attributes were docked on two GABA receptors (the alpha-1 subunit of GABAA-R and GBR1 subunit of GABAB R). Selected benzofuran derivatives were synthesized by a multistep procedure and characterized. To examine the neurotropic effects, mice were pretreated with different concentrations of the compounds prior to PTZ- or 4-AP-induced seizures. We assessed acute toxicity, motor behavior, and the effects on seizures. RESULTS: The tested ligands that complied with Lipinski's rule of five were tested in silico with GABAA-R (DeltaG = -5.51 to -5.84 kcal/mol) at the allosteric site for benzodiazepines. They bound to a similar cluster of residues as the reference compound (gaboxadol, DeltaG = -5.51 kcal/mol). Synthesis was achieved with good overall yields (42-9.7%). Two compounds were selected for biological tests (BZF-7 and rac-BZF-10) on a mouse model of seizures, induced by pentylenetetrazol (PTZ) or 4-aminopyridine (4-AP). PTZ-induced seizures are associated with GABA receptors, and those 4-AP-induced with the blockage of the delayed rectifier-type potassium channel, which promotes the release of the NMDA-sensitive glutamatergic ionotropic receptor and other neurotransmitters. The biological assays demonstrated that BZF-7 and rac-BZF-10 do not protect against seizures. Indeed, BZF-7 increased the number of PTZ-induced seizures and decreased latency time. The 4-AP model apparently showed a potentiation of seizure effects after administration of the BZF-analogues, evidenced by the incidence and severity of the seizures and reduced latency time. CONCLUSIONS: The results suggest that the test compounds are GABAergic antagonists with stimulatory activity on the CNS. PMID- 29792151 TI - Pyrazole and imidazo[1,2-b]pyrazole derivatives as new potential anti tuberculosis agents. AB - BACKGROUND: We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening showed that many compounds are able to totally inhibit Mycobacterium growth (>90 %). Among the most active compounds, we selected some new possible hits based on their similarities and, at the same time, their novelty respect to the pipeline drugs. METHODS: In order to increase the potency and obtain more information about structure activity relationship (SAR), we design and synthesized three new series of compounds (2a-e, 3a-e, and 4a-l). CONCLUSIONS: Performed tests confirmed that both new pyrazoles and imidazo pyrazoles could represent a new starting point to obtain more potent compounds and further work is now underway to identify the protein targets of this new class of anti-TB agents. PMID- 29792149 TI - Inhibition of Mutated Isocitrate Dehydrogenase 1 in Cancer. AB - BACKGROUND: R132H mutation of isocitrate dehydrogenase 1 (IDH1) is found in ~75% of low-grade gliomas and secondary glioblastomas as well as in several other types of cancer. More chemotypes of inhibitors of IDH1(R132H) are therefore needed. OBJECTIVE: The study aimed to develop a new class of IDH1(R132H) inhibitors as potent antitumor agents. METHOD: A biochemical assay was developed to find inhibitors of IDH1(R132H) mutant enzyme. Chemical synthesis and structure activity relationship studies were used to find compounds with improved potency. Antitumor activities of selected compounds were evaluated. RESULTS: A series of aromatic sulfonamide compounds was found to be novel, potent inhibitors of IDH1(R132H) with Ki values as low as 0.6 uM. Structure-activity relationships of these compounds are discussed. Enzyme kinetics studies showed that one compound is a competitive inhibitor against the substrate alpha-KG and a non-competitive inhibitor against the cofactor NADPH. Several inhibitors were found to have no activity against wild-type IDH1, showing a high selectivity. Two potent inhibitors exhibited strong activity against proliferation of BT142 glioma cells with IDH1 R132H mutation, while these compounds did not significantly affect the growth of glioma cells without IDH1 mutation. CONCLUSION: This novel series of IDH1(R132H) inhibitors have potential to be further developed for the treatment of glioma with IDH1 mutation. PMID- 29792152 TI - Sorbinil, an aldolase reductase inhibitor, in fighting against diabetic complications. AB - BACKGROUND: Aldose reductase (AR) is involved in pathogenesis of diabetes, which is one of the major threats to global public health. OBJECTIVE: In this review article, we have discussed the role of sorbinil, an AR inhibitor (ARI), in preventing diabetic complications. RESULTS: AR contributes in diabetes by generating excess intracellular superoxide and other mediators of oxidative stress through polyol pathway. Inhibition of AR activity thus might be potential approach for the management of diabetic complications. Experimental evidences indicated that sorbinil can decrease AR activity and inhibit polyol pathway. Both in vitro and animal model studies reported the efficacy of sorbinil in controlling the progression of diabetes. Moreover, Sorbinil has been found to be comparatively safer than other ARIs for human use. But, it is still in early phase testing for the treatment of diabetic complications clinically. CONCLUSION: Sorbinil is an effective ARI, which could play therapeutic role in treating diabetes and diabetic complications. However, advanced clinical trials are required for sorbinil so that it could be applied with the lowest efficacious dose in humans. PMID- 29792153 TI - Antimicrobial Evaluation of Erythrinan Alkaloids from Erythrina cristagalli L. AB - BACKGROUND: Several species of the genus Erythrina have been used as sedative, antidepressant, and anticonvulsant. Erythrina crista-galli is native to the Pampa Biome and is widely used for medicinal purposes. Erythrinan alkaloids exhibit a range of pharmacological properties. OBJECTIVE: The aim of this study was to evaluate the basic fractions and the alkaloids isolated from E. crista-galli bark against a collection of bacteria and fungi for the first time. METHODS: Erythrina crista-galli stem bark was extracted with MeOH under reflux. The crude extract was dissolved in water, acidified and extracted with diethyl ether. Basification of the aqueous solution followed by diethyl ether and ethyl acetate extractions gave the basic ether and basic ethyl acetate fractions. Chromatographic purification of these fractions afforded five known alkaloids: erytharbine (1), erysotrine (2), erysotramidine (3), erysotrine N-oxide (4) and erythratidine (5) along with a new alkaloid named here erythratidine N-oxide (6). Alkaloids 1-6 were investigated against a collection of bacteria and fungi using the broth micro dilution method. RESULTS: In this work, a new alkaloid was isolated from E. crista-galli. The most significant bacterial inhibitory effect of alkaloidal fractions was observed against the Gram-negative Pseudomas aeroginosa (MIC values of 31.25 ug.mL-1). Basic ether fraction displayed good antimicrobial activity against Shigella sonnei with MIC= 62.5 ug.mL-1. Isolated alkaloids 1-6 showed inhibitory activity against all bacteria tested (MIC values of 50-100 ug.mL-1). In addition, the crude extract and alkaloids 1, 2, and 5 also showed good antifungal potential against Candida krusei (MICs between 12.5 and 31.25 ug.mL 1). The previously undescribed alkaloid 6 presented MIC values between 50 and 100 ug.mL-1 against all tested microorganisms. CONCLUSION: In general, as with a considerable number of phytochemicals with antimicrobial activity, alkaloids 1-6 may be considered with potential as antibacterial/antifungal agents. The MIC values of the extract, alkaloidal fractions and compounds 1-6 indicate that, at least in part, the isolates were responsible for the antimicrobial activity observed. PMID- 29792154 TI - Exploration of (hetero)aryl derived thienylchalcones for antiviral and anticancer activities. AB - BACKGROUND: Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. OBJECTIVE: With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. METHOD: A focused set of thienyl chalcone derivaties II-VI was screened for selected viruses Hepatitis B virus (HBV), Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), Dengue virus 2 (DENV2), Influenza A (H1N1) virus, MERS coronavirus, Poliovirus 1 (PV 1), Rift Valley fever (RVF), Tacaribe virus (TCRV), Venezuelan equine encephalitis virus (VEE) and Zika virus (ZIKV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. Additionally, a cyclopropylquinoline derivative IV has been screened for 60 human cancer cell lines using the Development Therapeutics Program (DTP) of NCI. RESULTS: All thienyl chalcone derivatives II-VI displayed moderate to excellent antiviral activity towards several viruses tested. Compounds V and VI were turned out be active compounds towards human cytomegalovirus for both normal strain (AD169) as well as resistant isolate (GDGr K17). Particularly, cyano derivative V showed very high potency (EC50: <0.05 uM) towards AD169 strain of HCMV compared to standard drug Ganciclovir (EC50: 0.12 uM). Additionally, it showed moderate activity in the secondary assay (AD169; EC50: 2.30 uM). The cyclopropylquinoline derivative IV displayed high potency towards Rift Valley fever virus (RVFV) and Tacaribe virus (TCRV). The cyclopropylquinoline derivative IV is nearly 28 times more potent in our initial in vitro visual assay (EC50: 0.39 MUg/ml) and nearly 17 times more potent in neutral red assay (EC50: 0.71 MUg/ml) compared to the standard drug Ribavirin (EC50: 11 MUg/ml; visual assay and EC50: 12 MUg/ml; neutral red assay). It is nearly 12 times more potent in our initial in vitro visual assay (EC50: >1 MUg/ml) and nearly 8 times more potent in neutral red assay (EC50: >1.3 MUg/ml) compared to the standard drug Ribavirin (EC50: 12 MUg/ml; visual assay and EC50: 9.9 MUg/ml; neutral red assay) towards Tacaribe virus (TCRV). Additionally, cyclopropylquinoline derivative IV has shown strong growth inhibitory activity towards three major cancer (colon, breast, and leukemia) cell lines and moderate growth inhibition shown towards other cancer cell lines screened. CONCLUSION: Compounds V and VI were demonstrated viral inhibition towards Human cytomegalovirus, whereas cyclopropylquinoline derivative IV towards Rift Valley fever virus and Tacaribe virus. Additionally, cyclopropylquinoline derivative IV has displayed very good cytotoxicity against colon, breast and leukemia cell lines in vitro. PMID- 29792155 TI - Design, Synthesis and Investigation of New Diphenyl Substituted Pyridazinone Derivatives as Both Cholinesterase and Abeta-Aggregation Inhibitors. AB - : Backround: With respect to the increase in the average life expectancy, Alzheimer Disease (AD), the most common form of age-related dementia, has become a major threat to the population over the age of 65 during the past several decades. The majority of AD treatments are focused on cholinergic and amyloid hypotheses. OBJECTIVE: In this study, three series of diphenyl-2-(2-(4 substitutedpiperazin-1-yl)ethyl)pyridazin-3(2H)-one derivatives were designed, synthesized and investigated for their ability to inhibit both cholinesterase enzymes and amyloid-beta aggregation. METHOD: The inhibitory activities of the synthesized compounds on AChE (from electric eel) and BChE (from equine serum) were determined by the modified Ellman's method. The reported thioflavin T-based fluorometric assay was performed to investigate the effect of the selected compounds on the aggregation of Abeta1-42. The cytotoxic effect of the compounds (4g, 11g and 18g) was monitored in 3T3 cell lines to gain insight into therapeutic potential of the compounds by using MTT assay. The crystal structures of the AChE (1EVE) and BChE (1P0I) enzymes were retrieved from the RCSB Protein Data Bank and Molecular Operating Environment (MOE) software was used for molecular docking of the ligands. RESULTS: Among the tested compounds, 5,6 diphenyl derivative 18g was identified as the most potent and selective AChE inhibitor (IC50 = 1.75 uM, Selectivity Index for AChE > 22.857). 4,6-Diphenyl derivative 11g showed the highest and the most selectivity for BChE (IC50= 4.97 uM, SI for AChE < 0.124). Interestingly, 4,5-diphenyl derivative 4g presented dual cholinesterase inhibition (AChE IC50= 5.11 uM; BChE IC50= 14.16 uM, SI for AChE = 2.771). CONCLUSION: Based on biological activity results and low toxicity of the compounds, it can be said that diphenyl substituted pyridazinone core is a valuable scaffold. Especially, dual inhibitory potencies of 4,5-diphenylpyridazin 3(2H)-one core for the cholinesterase enzymes and Abeta-aggregation makes this core a promising disease-modifying agent. PMID- 29792156 TI - Design, synthesis and biological evaluation of 1H-1,2,3-Triazole-Linked-1H Dibenzo[b,h]xanthenes as Inductors of ROS-Mediated Apoptosis in the Breast Cancer Cell Line MCF-7. AB - BACKGROUND: Low molecular weight 1,2,3-triazoles and naphthoquinones are endowed with various types of biological activity, such as against cancer, HIV and bacteria. However, in some cases, the conjugation of these two nuclei considerably increases their biological activities Objective: In this work, we decided to study the synthesis and screening of bis-naphthoquinones and xanthenes tethered to 1,2,3-triazoles against cancer cell lines, specifically the human breast cancer cell line MCF-7. RESULTS: Starting from lawsone and aryl-1H-1,2,3 triazole-4-carbaldehydes (10a-h) several new 7-(1-aryl-1H-1,2,3-triazol-4-yl)-6H dibenzo[b,h]xanthene-5,6,8,13(7H)-tetraones (12a-h) and 3,3'-((1-aryl-1H 1,2,3-triazol-4-yl)methylene)bis(2-hydroxynaphthalene-1,4-diones) 11a-h were synthesized and evaluated for their cytotoxic activities using the human breast cancer cell line MCF-7 and the non-tumor cell line MCF10A as control. We performed test of cell viability, cell proliferation, intracellular ATP content and cell cytometry to determine reactive oxygen species (ROS) formation. CONCLUSIONS: Based on these results, we found that compound 12a promote ROS production, interfering with energy metabolism, cell viability and proliferation, and thus promoting an whole cell damage. PMID- 29792157 TI - Long-term health and germline transmission in transgenic cattle following transposon-mediated gene transfer. AB - BACKGROUND: Transposon-mediated, non-viral gene delivery is a powerful tool for generating stable cell lines and transgenic animals. However, as multi-copy insertion is the preferred integration pattern, there is the potential for uncontrolled changes in endogenous gene expression and detrimental effects in cells or animals. Our group has previously reported on the generation of several transgenic cattle by using microinjection of the Sleeping Beauty (SB) and PiggyBac (PB) transposons and seeks to explore the long-term effects of this technology on cattle. RESULTS: Transgenic cattle, one female (SNU-SB-1) and one male (SNU-PB-1), reached over 36 months of age with no significant health issues and normal blood parameters. The detection of transgene integration and fluorescent signal in oocytes and sperm suggested the capacity for germline transmission in both of the founder animals. After natural breeding, the founder transgenic cow delivered a male calf and secreted milk containing fluorescent transgenic proteins. The calf expressed green fluorescent protein in primary cells from ear skin, with no significant change in overall genomic stability and blood parameters. Three sites of transgene integration were identified by next generation sequencing of the calf's genome. CONCLUSIONS: Overall, these data demonstrate that transposon-mediated transgenesis can be applied to cattle without being detrimental to their long-term genomic stability or general health. We further suggest that this technology may be usefully applied in other fields, such as the generation of transgenic animal models. PMID- 29792158 TI - Landraces of snake melon, an ancient Middle Eastern crop, reveal extensive morphological and DNA diversity for potential genetic improvement. AB - BACKGROUND: Snake melon (Cucumis melo var. flexuosus, "Faqqous") is a traditional and ancient vegetable in the Mediterranean area. A collection of landraces from 42 grower fields in Israel and Palestinian territories was grown and characterized in a "Common Garden" rain-fed experiment, at the morphological horticultural and molecular level using seq-DArT markers. RESULTS: The different landraces ("populations") showed extensive variation in morphology and quantitative traits such as yield and femaleness, and clustered into four horticultural varieties. Yield was assessed by five harvests along the season, with middle harvests producing the highest yields. Yield correlated with early vigor, and with femaleness, but not with late vigor. At the molecular level, 2784 SNP were produced and > 90% were mapped to the melon genome. Populations were very polymorphic (46-72% of the markers biallelic in a 4 individuals sample), and observed heterozygosity was higher than the expected, suggesting gene flow among populations and extensive cross pollination among individuals in the field. Genetic distances between landraces were significantly correlated with the geographical distance between collecting sites, and with long term March precipitation average; variation in yield correlated with April temperature maxima. CONCLUSIONS: The extensive variation suggests that selection of local snake melon could result in yield improvement. Correlations between traits and climatic variables could suggest local adaptation of landraces to the diverse environment in which they evolved. This study stresses the importance of preserving this germplasm, and its potential for breeding better snake melons as an heirloom crop in our region. PMID- 29792159 TI - On the possibility of death of new genes - evidence from the deletion of de novo microRNAs. AB - BACKGROUND: New genes are constantly formed, sometimes from non-genic sequences, creating what is referred to as de novo genes. Since the total number of genes remains relatively steady, gene deaths likely balance out new births. In metazoan genomes, microRNAs (miRs) genes, small and non-coding, account for the bulk of functional de novo genes and are particularly suited to the investigation of gene death. RESULTS: In this study, we discover a Drosophila-specific de novo miRNA (mir-977) that may be facing impending death. Strikingly, after this testis specific gene is deleted from D. melanogaster, most components of male fitness increase, rather than decrease as had been expected. These components include male viability, fertility and males' ability to repress female re-mating. Given that mir-977 has a negative fitness effect in D. melanogaster, this de novo gene with an adaptive history for over 60 Myrs may be facing elimination. In some other species where mir-977 is not found, gene death may have already happened. CONCLUSION: The surprising result suggests that de novo genes, constantly rising and falling during evolution, may often be transiently adaptive and then purged from the genome. PMID- 29792160 TI - NextSV: a meta-caller for structural variants from low-coverage long-read sequencing data. AB - BACKGROUND: Structural variants (SVs) in human genomes are implicated in a variety of human diseases. Long-read sequencing delivers much longer read lengths than short-read sequencing and may greatly improve SV detection. However, due to the relatively high cost of long-read sequencing, it is unclear what coverage is needed and how to optimally use the aligners and SV callers. RESULTS: In this study, we developed NextSV, a meta-caller to perform SV calling from low coverage long-read sequencing data. NextSV integrates three aligners and three SV callers and generates two integrated call sets (sensitive/stringent) for different analysis purposes. We evaluated SV calling performance of NextSV under different PacBio coverages on two personal genomes, NA12878 and HX1. Our results showed that, compared with running any single SV caller, NextSV stringent call set had higher precision and balanced accuracy (F1 score) while NextSV sensitive call set had a higher recall. At 10X coverage, the recall of NextSV sensitive call set was 93.5 to 94.1% for deletions and 87.9 to 93.2% for insertions, indicating that ~10X coverage might be an optimal coverage to use in practice, considering the balance between the sequencing costs and the recall rates. We further evaluated the Mendelian errors on an Ashkenazi Jewish trio dataset. CONCLUSIONS: Our results provide useful guidelines for SV detection from low coverage whole-genome PacBio data and we expect that NextSV will facilitate the analysis of SVs on long read sequencing data. PMID- 29792161 TI - A website to identify shared genes in Saccharomyces cerevisiae homozygous deletion library screens. AB - BACKGROUND: The homozygous yeast deletion library includes approximately 4800 diploid strains each containing one deleted non-essential gene. Hundreds of publications have arisen through experimentation using this genome-wide biological resource. As part of this work over 677 genesets have been collated from these experiments representing the phenotypic responses of the library to a diverse set of chemical and physical challenges. DESCRIPTION: A website called the Saccharomyces cerevisiae Homozygous Deletion Library Tools (ScHo DeLiTo-96) has been developed with the primary goal of browsing and identifying genes shared between these responsive phenotypes (available at yeastdb.org ). Geneset comparisons have been performed for each phenotype against all others to identify common genes. Genesets and other curated information are stored in a relational database and a website interface allows users to query and browse the data in an intuitive way to reveal commonality between selected phenotypic responses. The most commonly occurring genes in all of the stored phenotypes are highly over represented in the GO slim term "cellular ion homeostasis" indicating that genes shared between phenotypes may highlight a common cellular response. Additionally, user derived genesets can be uploaded and intersected against the stored data to reveal common responses which may otherwise have been obscure. CONCLUSION: These tools provide a simple method to perform niche enquiries between datasets derived from the yeast deletion library. PMID- 29792162 TI - Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones. AB - BACKGROUND: The sense of smell is unrivaled in terms of molecular complexity of its input channels. Even zebrafish, a model vertebrate system in many research fields including olfaction, possesses several hundred different olfactory receptor genes, organized in four different gene families. For one of these families, the initially discovered odorant receptors proper, segregation of expression into distinct spatial subdomains within a common sensory surface has been observed both in teleost fish and in mammals. However, for the remaining three families, little to nothing was known about their spatial coding logic. Here we wished to investigate, whether the principle of spatial segregation observed for odorant receptors extends to another olfactory receptor family, the V2R-related OlfC genes. Furthermore we thought to examine, how expression of OlfC genes is integrated into expression zones of odorant receptor genes, which in fish share a single sensory surface with OlfC genes. RESULTS: To select representative genes, we performed a comprehensive phylogenetic study of the zebrafish OlfC family, which identified a novel OlfC gene, reduced the number of pseudogenes to 1, and brought the total family size to 60 intact OlfC receptors. We analyzed the spatial pattern of OlfC-expressing cells for seven representative receptors in three dimensions (height within the epithelial layer, horizontal distance from the center of the olfactory organ, and height within the olfactory organ). We report non-random distributions of labeled neurons for all OlfC genes analysed. Distributions for sparsely expressed OlfC genes are significantly different from each other in nearly all cases, broad overlap notwithstanding. For two of the three coordinates analyzed, OlfC expression zones are intercalated with those of odorant receptor zones, whereas in the third dimension some segregation is observed. CONCLUSION: Our results show that V2R-related OlfC genes follow the same spatial logic of expression as odorant receptors and their expression zones intermingle with those of odorant receptor genes. Thus, distinctly different expression zones for individual receptor genes constitute a general feature shared by teleost and tetrapod V2R/OlfC and odorant receptor families alike. PMID- 29792163 TI - Different patterns of inflammatory and angiogenic factors are associated with peritoneal small solute transport and peritoneal protein clearance in peritoneal dialysis patients. AB - BACKGROUND: Both peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties. METHODS: Stable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl. RESULTS: A total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 +/- 14.2 years and a median PD duration of 32.5 (9.0 56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl. CONCLUSIONS: MTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors. PMID- 29792164 TI - A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10. AB - BACKGROUND: Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. CASE PRESENTATION: This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. CONCLUSIONS: When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10. PMID- 29792165 TI - Molecular characterization and differential expression suggested diverse functions of P-type II Ca2+ATPases in Triticum aestivum L. AB - BACKGROUND: Plant P-type II Ca2+ATPases are formed by two distinct groups of proteins (ACAs and ECAs) that perform pumping of Ca2+ outside the cytoplasm during homeostasis, and play vital functions during development and stress management. In the present study, we have performed identification and characterisation of P-type II Ca 2+ ATPase gene family in an important crop plant Triticum aestivum. RESULTS: Herein, a total of 33 TaACA and 9 TaECA proteins were identified from the various chromosomes and sub-genomes of Triticum aestivum. Phylogenetic analysis revealed clustering of the homoeologous TaACA and TaECA proteins into 11 and 3 distinct groups that exhibited high sequence homology and comparable structural organization as well. Both TaACA and TaECA group proteins consisted of eight to ten transmembrane regions, and their respective domains and motifs. Prediction of sub-cellular localization was found variable for most of the proteins; moreover, it was consistent with the evolutionarily related proteins from rice and Arabidopsis in certain cases. The occurrence of assorted sets of cis-regulatory elements indicated their diverse functions. The differential expression of various TaACA and TaECA genes during developmental stages suggested their roles in growth and development. The modulated expression during heat, drought, salt and biotic stresses along with the occurrence of various stress specific cis-regulatory elements suggested their association with stress response. Interaction of these genes with numerous development and stress related genes indicated their decisive role in various biological processes and signaling. CONCLUSION: T. aestivum genome consisted of a maximum of 42 P-type II Ca 2+ ATPase genes, derived from each A, B and D sub-genome. These genes may play diverse functions during plant growth and development. They may also be involved in signalling during abiotic and biotic stresses. The present study provides a comprehensive insight into the role of P-type II Ca 2+ ATPase genes in T. aestivum. However, the specific function of each gene needs to be established, which could be utilized in future crop improvement programs. PMID- 29792168 TI - Trends in the incidence and associated factors of late-onset sepsis associated with improved survival in extremely preterm infants born at 23-26 weeks' gestation: a retrospective study. AB - BACKGROUND: To investigate the trends in the incidence and associated factors of late-onset sepsis (LOS) associated with improved survival in extremely preterm infants. METHODS: Medical records of 364 infants who were born at 23-26 weeks' gestation from 2000 to 2005 (period I, n = 124) and from 2006 to 2011 (period II, n = 240) were retrospectively reviewed. The infants were stratified into subgroups of 23-24 and 25-26 weeks' gestation within each period, and survival, LOS rate, and clinical characteristics were analyzed. Multivariate logistic regression analyses were completed to identify the clinical factors associated with LOS. RESULTS: The survival rate of 75.8% during period I significantly improved to 85.4% during period II, especially in infants at 23-24 weeks' gestation (55.1% vs. 78.1%, respectively). The LOS rate of 33.1% during period I significantly reduced to 15.8% during period II, especially in infants at 25-26 weeks' gestation (32.0% vs. 8.9%, respectively). The LOS rate per 1000 hospital days of 4.0 during period I significantly reduced to 1.8 during period II. Candida presence reduced from 21.3% during period I to 4.7% during period II. In multivariate analyses, during period I, prolonged intubation, especially in infants at 25-26 weeks' gestation, and necrotizing enterocolitis, especially in infants at 23-24 weeks' gestation, were significantly associated with LOS. CONCLUSIONS: Improved survival of infants at 23-24 weeks' gestation was associated with a simultaneous reduction of LOS incidence in infants at 25-26 weeks' gestation. Less-invasive assisted ventilation may be one of the details of improved perinatal and neonatal care that has contributed to lowering risk of infection or death among periviable infants. PMID- 29792167 TI - Association between glaucoma severity and driving cessation in subjects with primary open-angle glaucoma. AB - BACKGROUND: The aim of this study, which included a baseline cross-sectional study and a 3-year follow-up prospective study, was to investigate the association between glaucomatous visual field damage and driving cessation in subjects with primary open-angle glaucoma (POAG). METHODS: A total of 211 POAG subjects divided into 3 groups according to POAG severity (mild, moderate, or severe) in the better eye were enrolled along with 148 control subjects; subjects were asked about changes in their driving status. In the 3-year follow-up study, 185 of the POAG subjects and 80 of the controls annually reported their driving status. Adjusted odds ratios and 95% confidence intervals for the prevalence and incidence of driving cessation were estimated with a multiple logistic regression model. RESULTS: In the original cross-sectional study, 11/148 (7%) members of the control group reported having given up driving over the previous 5 years; the corresponding figures for the mild POAG, moderate POAG, and severe POAG groups were 9/173 (5%), 0/22 (0%), and 5/16 (31%), respectively (p = 0.001, Fisher's exact test), with severe POAG found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (odds ratio 11.52 [95% CI 2.87-46.35], ref. control, p = 0.001). In the follow-up study, the proportions of subjects who ceased driving were 1/80 (1.3%) in the control group, 8/152 (5.3%) in the mild POAG group, 5/22 (22.7%) in the moderate POAG group, and 2/11 (18.2%) in the severe POAG group (p = 0.001, Fisher's exact test). Moderate POAG and severe POAG in the better eye were found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (moderate POAG in the better eye: odds ratio 37.7 [95% CI 3.7-383.8], ref. control, p = 0.002, and severe POAG in the better eye: odds ratio 52.8 [95% CI 3.5-797.0], ref. control, p = 0.004). CONCLUSION: Moderate and Severe POAG in the better eye is associated with driving cessation. PMID- 29792166 TI - The PDGFRbeta/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer. AB - BACKGROUND: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. METHODS: The expression of CDCP1, PDGFRbeta and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRbeta was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFRbeta in TNBC clinical samples. RESULTS: We discovered that PDGF-BB-mediated activation of PDGFRbeta increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock down of PDGFRbeta in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFRbeta immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFRbeta axis in the modulation of CDCP1 expression. CONCLUSION: We have identified PDGF BB/PDGFRbeta-mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFRbeta and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs. PMID- 29792169 TI - Use of synthetic adrenocorticotropic hormone in patients with IgA nephropathy. AB - BACKGROUND: Synthetic adrenocorticotropic hormone (ACTH) has been demonstrated to be effective in patients with membranous nephropathy, minimal change disease and some histological subtypes of focal segmental glomerulosclerosis. Its clinical impact in patients with IgA nephropathy is currently unclear. CASE PRESENTATION: In this report, we describe the clinical use of ACTH in patients with IgA nephropathy. Three female patients (24-44 years) with overt proteinuria received intramuscular (IM) ACTH for varying time periods (8-14 months). Pre-treatment urine protein varied from 2.9 g/d to 4.3 g/d. CONCLUSIONS: There was complete remission in one patient on ACTH monotherapy and in the other two when prescribed as a steroid-sparing agent in combination with cyclophosphamide. All three had resolution in proteinuria to less than 1 g/d and maintained their GFR to baseline values. There were no reported side effects at a once a week dose. This study illustrates that ACTH is an effective agent that is well tolerated with minimal side effects and can be used as an alternative to prednisone in patients with IgA nephropathy. PMID- 29792170 TI - Liddle's-like syndrome associated with nephrotic syndrome secondary to membranous nephropathy: the first case report. AB - BACKGROUND: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) beta or gamma subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria. CASE PRESENTATION: A 65-year-old Japanese man presented with nephrotic syndrome. He had no remarkable family history, but had a medical history of hypertension and hyperlipidemia. On admission, hypertension, spironolactone-resistant hypokalemia (2.43 mEq/l), hyporeninemic hypoaldosteronism, and metabolic alkalosis, which suggested Liddle's syndrome, were observed. Treatment with triamterene together with a steroid for nephrotic syndrome resulted in rapid and remarkable effective on improvements of hypertension, hypokalemia, and edema of the lower extremities. Renal biopsy revealed membranous nephropathy (MN) as the cause of nephrotic syndrome, and advanced gastric cancer was identified on screening examination for cancers that could be associated with the development of MN. After total gastrectomy, triamterene was not required and proteinuria decreased. A mutation in the beta or gamma subunits of the ENaC gene was not identified. CONCLUSION: We reported for the first time a case of Liddle's-like syndrome associated with nephrotic syndrome secondary to MN. Aberrant activation of ENaC was suggested transient during the period of high proteinuria, and the activation was reversible with a decrease in proteinuria. PMID- 29792172 TI - Oral health and orofacial pain in people with dementia admitted to acute hospital wards: observational cohort study. AB - BACKGROUND: Orofacial pain in people with dementia is difficult to detect, and often under-treated. Our aim was to investigate the prevalence of orofacial pain in people with dementia in acute hospitals in the UK. Secondary aims were to examine oral health status and explore associations between orofacial pain and oral health factors. METHODS: This cross-sectional observational study was carried out in two UK hospitals. Using the Orofacial Pain Scale in Non-Verbal Individuals (OPS-NVI) to identify orofacial pain, 101 participants with dementia, admitted to acute medical wards, were observed for at least 3 min during rest and chewing. Verbal participants were then asked about presence of orofacial pain, using self-report pain scales. Finally, a brief oral assessment was performed. RESULTS: Orofacial pain, assessed with the OPS-NVI, was present in 11.9% (95% C.I. 5.9, 18.8) of participants at rest and 21.9% (95% C.I. 14.6, 31.3) whilst chewing. Participants who were no longer able to self-report pain were significantly more likely to experience orofacial pain. Oral health in both dentate and edentate participants was poor. Brush frequency, indication of chewing quality, consistency of the food, presence of extra-oral abnormalities, person who performed mouth care, and oral hygiene in dentate participants were significant predictors for the presence of orofacial pain. CONCLUSION: Improving oral care in acute hospital patients with dementia, particularly those who cannot self-report pain, may significantly reduce pain and suffering in this population. PMID- 29792171 TI - Embryonic transcriptome and proteome analyses on hepatic lipid metabolism in chickens divergently selected for abdominal fat content. AB - BACKGROUND: In avian species, liver is the main site of de novo lipogenesis, and hepatic lipid metabolism relates closely to adipose fat deposition. Using our fat and lean chicken lines of striking differences in abdominal fat content, post hatch lipid metabolism in both liver and adipose tissues has been studied extensively. However, whether molecular discrepancy for hepatic lipid metabolism exists in chicken embryos remains obscure. RESULTS: We performed transcriptome and proteome profiling on chicken livers at five embryonic stages (E7, E12, E14, E17 and E21) between the fat and lean chicken lines. At each stage, 521, 141, 882, 979 and 169 differentially expressed genes were found by the digital gene expression, respectively, which were significantly enriched in the metabolic, PPAR signaling and fatty acid metabolism pathways. Quantitative proteomics analysis found 20 differentially expressed proteins related to lipid metabolism, PPAR signaling, fat digestion and absorption, and oxidative phosphorylation pathways. Combined analysis showed that genes and proteins related to lipid transport (intestinal fatty acid-binding protein, nucleoside diphosphate kinase, and apolipoprotein A-I), lipid clearance (heat shock protein beta-1) and energy metabolism (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and succinate dehydrogenase flavoprotein subunit) were significantly differentially expressed between the two lines. CONCLUSIONS: For hepatic lipid metabolism at embryonic stages, molecular differences related to lipid transport, lipid clearance and energy metabolism exist between the fat and lean chicken lines, which might contribute to the striking differences of abdominal fat deposition at post-hatch stages. PMID- 29792174 TI - Perspectives on clinical use of bioimpedance in hemodialysis: focus group interviews with renal care professionals. AB - BACKGROUND: Inadequate volume control may be a main contributor to poor survival and high mortality in hemodialysis patients. Bioimpedance measurement has the potential to improve fluid management, but several dialysis centers lack an agreed fluid management policy, and the method has not yet been implemented. Our aim was to identify renal care professionals' perceived barriers and facilitators for use of bioimpedance in clinical practice. METHODS: Qualitative data were collected through four focus group interviews with 24 renal care professionals: dieticians, nephrologists and nurses, recruited voluntarily from a nation-wide selection of hemodialysis centers, having access to a bioimpedance-device. The participants were connected to each other and a moderator via equipment for telemedicine and the sessions were recorded. The interviews were semi-structured, focusing on the participants' perceptions of use of bioimpedance in clinical practice. Thematic content analysis was performed in consecutive steps, and data were extracted by employing an inductive, interactive, comparative process. RESULTS: Several barriers and facilitators to the use of bioimpedance in clinical practice were identified, and a multilevel approach to examining barriers and incentives for change was found to be applicable to the ideas and categories that arose from the data. The determinants were categorized on five levels, and the different themes of the levels illustrated with quotations from the focus groups participants. CONCLUSIONS: Determinants for use of bioimpedance were identified on five levels: 1) the innovation itself, 2) the individual professional, 3) the patient, 4) the social context and 5) the organizational context. Barriers were identified in the areas of credibility, awareness, knowledge, self-efficacy, care processes, organizational structures and regulations. Facilitators were identified in the areas of the innovation's attractiveness, advantages in practice, and collaboration. Motivation, team processes and organizational capacities appeared as both barriers and facilitators. PMID- 29792173 TI - Impact of growth pH and glucose concentrations on the CodY regulatory network in Streptococcus salivarius. AB - BACKGROUND: Streptococcus salivarius is an abundant isolate of the human oral microbiota. Since both pH and glucose availability fluctuate frequently in the oral cavity, the goal of this study was to investigate regulation by CodY, a conserved pleiotropic regulator of Gram positive bacteria, in response to these two signals. The chemostat culture system was employed to precisely control the growth parameters, and the transcriptomes of wild-type S. salivarius 57.I and its CodY-null derivative (DeltacodY) grown at pH 7 and 5.5, with limited and excessive glucose supply were determined. RESULTS: The transcriptomic analysis revealed that CodY was most active at pH 7 under conditions of glucose limitation. Based on whether a CodY binding consensus could be located in the 5' flanking region of the identified target, the transcriptomic analysis also found that CodY shaped the transcriptome via both direct and indirect regulation. Inactivation of codY reduced the glycolytic capacity and the viability of S. salivarius at pH 5.5 or in the presence of H2O2. Studies using the Galleria mellonella larva model showed that CodY was essential for the toxicity generated from S. salivarius infection, suggesting that CodY regulation was critical for immune evasion and systemic infections. Furthermore, the CodY-null mutant strain exhibited a clumping phenotype and reduced attachment in biofilm assays, suggesting that CodY also modulates cell wall metabolism. Finally, the expression of genes belonging to the CovR regulon was affected by codY inactivation, but CodY and CovR regulated these genes in opposite directions. CONCLUSIONS: Metabolic adaptation in response to nutrient availability and growth pH is tightly linked to stress responses and virulence expression in S. salivarius. The regulation of metabolism by CodY allows for the maximal utilization of available nutrients and ATP production. The counteractive regulation of the CovR regulon could fine tune the transcriptomes in response to environmental changes. PMID- 29792175 TI - Pulse actinomycin D as first-line treatment of low-risk post-molar non choriocarcinoma gestational trophoblastic neoplasia. AB - BACKGROUND: Little data exists predicting the resistance to actinomycin D (Act-D) single-agent for gestational trophoblastic neoplasia (GTN). The objective was to determine the overall success of pulse Act-D and the factors predictive of resistance to pulse Act-D in the treatment of low-risk, non-choriocarcinoma post molar GTN. METHODS: From January 2013 to October 2016, according to the FIGO criteria for the diagnosis of post-molar disease and the FIGO risk-factor scoring system for GTN, a total of 135 patients with post-molar non-choriocarcinoma GTN who were chemotherapy-naive with a FIGO score < 7 were treated with single-agent pulse Act-D as a first-line regimen, in Peking Union Medical College Hospital. The pulse Act-D regimen is defined as 1.25 mg/m2 (max 2 mg) IV push every other week. All patients were followed until May 2017. Epidemiological and clinical data were compared between patients with remission and resistance to Act-D to determine predictive factors by univariate and multivariate analysis. RESULTS: Ninety-six of 135 patients (71.1%) achieved complete remission after first-line chemotherapy of pulse Act-D. In multivariate analysis, existing invasive uterine lesions observed by pre-chemotherapy transvaginal ultrasound (odds ratio [OR] 7.5, 95% confidence intervals [CI] 2.7-20.8), FIGO score >= 5 (OR 15.2, 95% CI 1.5-156.1) and pre-chemotherapy levels of beta-hCG >= 4000 IU/L (OR 3.1, 95% CI 1.2-8.3) were independent high-risk factors predicting resistance to pulse Act-D as single-agent chemotherapy. During follow-up, no relapse, treatment-associated serious adverse events, or death occurred. CONCLUSIONS: As first-line chemotherapy, pulse Act-D was effective and tolerable for patients with low-risk post-molar non-choriocarcinoma. Existing invasive uterine lesions observed by pre chemotherapy transvaginal ultrasound, a FIGO score >= 5, and pre-chemotherapy levels of beta-hCG >= 4000 IU/L were independent factors for resistance to pulse Act-D. PMID- 29792176 TI - Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis with detection of myeloperoxidase and phospholipase A2 receptor in membranous nephropathy lesions: report of two patients with microscopic polyangiitis. AB - BACKGROUND: Podocyte phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic adult membranous nephropathy (MN). Histological PLA2R staining in the renal tissue has proven to be useful for the detection of idiopathic MN. However, glomerular PLA2R deposits have also been recently observed in several patients with secondary MN, such as hepatitis B virus-associated, hepatitis C virus-associated, and neoplasm-associated MN. Certain inflammatory environments have been suggested to lead to abnormal expression of PLA2R epitopes, with the resulting production of PLA2R autoantibodies. CASE PRESENTATION: We report two patients diagnosed with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis with MN-lesions, in whom ANCA titers for myeloperoxidase (MPO) were persistently positive. The first patient was a 52-years-old man who presented with interstitial pneumonitis. Microscopic hematuria and proteinuria were found when the interstitial pneumonitis became more severe. Renal biopsy findings yielded a diagnosis of ANCA-associated glomerulonephritis (mixed class) with MN-lesions. The second patient was a 63-years-old woman who had been treated for relapsing polychondritis. Her renal tissue showed evidence of focal ANCA associated glomerulonephritis with MN-lesions. Interestingly, both MPO and PLA2R were detected in the glomerular subepithelial deposits of both patients. Immunoglobulin G (IgG) 1 and IgG2 were positive in the glomeruli of patient 2, and all subclasses of IgGs were positive in patient 1. CONCLUSION: The present cases suggest that ANCA-associated glomerulonephritis could expose PLA2R, leading to the development of MN-lesions. PMID- 29792178 TI - Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative miller fisher syndrome and Bickerstaff brainstem encephalitis: a case report. AB - BACKGROUND: Guillain-Barre syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes. CASE PRESENTATION: We report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode. CONCLUSION: This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder. PMID- 29792179 TI - Hopkins syndrome following the first episode of bronchial asthma associated with enterovirus D68: a case report. AB - BACKGROUND: Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection. CASE PRESENTATION: A 5-year-old girl developed acute respiratory distress. On the fourth hospital day, both her legs became paralyzed except for slight muscle contraction in the right lower limb. Tendon reflexes in the lower limbs were diminished and there was a positive Babinski sign on the right. Sensation was normal in all modalities, and there was no uro-rectal disturbance. Spinal magnetic resonance imaging identified T2-hyperintense lesions with spinal cord edema, mainly involving the bilateral T11 to L1 anterior horns, with left side dominance extending to the left posterior horn. The neurological and neuro-radiological findings of our case were suggestive of HS; however, she had no history of bronchial asthma. An acetylcholine inhalation challenge eventually proved the presence of reversible airway hyper-responsiveness, allowing us to diagnose HS. We identified enterovirus D68 in the patient's intratracheal aspirates using a sensitive polymerase chain reaction assay. Intravenous immunoglobulin administrations at 2 g/kg2 for 5 consecutive days were repeated every month up to four times. After these treatments, the muscle strength of her right lower limb slightly improved while her left lower leg remained completely paralyzed. CONCLUSION: This case emphasizes the importance of provocation tests to reveal the presence of airway hyper-responsiveness when a child shows neurological signs mimicking HS following acute respiratory distress. Furthermore, the present case suggests a possible link between HS and acute flaccid paralysis following lower respiratory tract infection by enterovirus D68. PMID- 29792180 TI - Screening for congenital fetal anomalies in low risk pregnancy: the Kenyatta National Hospital experience. AB - BACKGROUND: Congenital malformations contribute significantly to the disease burden among children globally. A study conducted in Kenya on understanding the burden of surgical congenital anomalies, highlights the need for Kenyan health systems to go beyond the medical dimensions of illness. This could be achieved by linking knowledge of the severe congenital anomalies (CAs) and their impact of varying disability to the delivery of local health services and public health program planning. Subsequently, early detection of these congenital anomalies is vital and can be achieved through fetal ultrasonography. Studies have proven that antenatal ultrasound can successfully diagnose fetal abnormalities in many cases and therefore aid in counseling of parents and planning for early intervention. Although there are studies on screening of congenital anomalies in various populations, very few have been done in the African population and none to the best of our knowledge has been done in Kenya. METHODS: The patients, who underwent routine obstetric ultrasounds, were recruited into the study. The study population comprised patients who were referred from the obstetric clinic, casualty and other clinics within the hospital vicinity. Data of antenatal ultrasounds was statistically analyzed on structured data collection form to determine the prevalence of congenital anomalies. RESULTS: Fifteen fetal anomalies were diagnosed in 500 women who came for routine ultrasound (3%). The mean age of the mothers was 28.2 years (SD +/- 4.5) with an age range from 15 to 44 years. 400 (80%) of the mothers were aged between 27 and 34 years. The most frequently observed fetal anomalies involved the head (8/ 500; 1.6%). Each of the remaining anomalies affected less than 1% of the fetuses and included anomalies of the spine (2/ 500; 0.4%), pulmonary (2/ 500; 0.4%), renal and urinary tract (2/ 500; 0.4%) and skeletal systems (2/ 500; 0.4%). Majority, 9 of 15 (60%) of the fetuses with anomalies detected on prenatal ultrasound resulted in postnatal mortality within days of delivery. CONCLUSION: Congenital anomalies prevalence in our setting compares with those found in other studies. From this study, major birth defects are a major cause of perinatal mortality. PMID- 29792177 TI - Investigation of the thermophilic mechanism in the genus Porphyrobacter by comparative genomic analysis. AB - BACKGROUND: Type strains of the genus Porphyrobacter belonging to the family Erythrobacteraceae and the class Alphaproteobacteria have been isolated from various environments, such as swimming pools, lake water and hot springs. P. cryptus DSM 12079T and P. tepidarius DSM 10594T out of all Erythrobacteraceae type strains, are two type strains that have been isolated from geothermal environments. Next-generation sequencing (NGS) technology offers a convenient approach for detecting situational types based on protein sequence differences between thermophiles and mesophiles; amino acid substitutions can lead to protein structural changes, improving the thermal stabilities of proteins. Comparative genomic studies have revealed that different thermal types exist in different taxa, and few studies have been focused on the class Alphaproteobacteria, especially the family Erythrobacteraceae. In this study, eight genomes of Porphyrobacter strains were compared to elucidate how Porphyrobacter thermophiles developed mechanisms to adapt to thermal environments. RESULTS: P. cryptus DSM 12079T grew optimally at 50 degrees C, which was higher than the optimal growth temperature of other Porphyrobacter type strains. Phylogenomic analysis of the genus Porphyrobacter revealed that P. cryptus DSM 12079T formed a distinct and independent clade. Comparative genomic studies uncovered that 1405 single-copy genes were shared by Porphyrobacter type strains. Alignments of single-copy proteins showed that various types of amino acid substitutions existed between P. cryptus DSM 12079T and the other Porphyrobacter strains. The primary substitution types were changes from glycine/serine to alanine. CONCLUSIONS: P. cryptus DSM 12079T was the sole thermophile within the genus Porphyrobacter. Phylogenomic analysis and amino acid frequencies indicated that amino acid substitutions might play an important role in the thermophily of P. cryptus DSM 12079T. Bioinformatic analysis revealed that major amino acid substitutional types, such as changes from glycine/serine to alanine, increase the frequency of alpha-helices in proteins, promoting protein thermostability in P. cryptus DSM 12079T. Hence, comparative genomic analysis broadens our understanding of thermophilic mechanisms in the genus Porphyrobacter and may provide a useful insight in the design of thermophilic enzymes for agricultural, industrial and medical applications. PMID- 29792181 TI - Six underlying health conditions strongly influence mortality based on pneumonia severity in an ageing population of Japan: a prospective cohort study. AB - BACKGROUND: Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. METHODS: Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age >= 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. RESULTS: In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28-14.99), recent hospitalization (2.21; 1.36-3.60), age >= 85 years (2.15; 1.08-4.28), low body mass index (1.99, 1.25 3.16), neoplastic disease (1.82; 1.17-2.85), and male gender (1.78; 1.16-2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0-10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 >= 3) (risk ratio: 7.24, 95%CI: 3.08-25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94-2.50). CONCLUSIONS: Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion. PMID- 29792182 TI - BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues. AB - BACKGROUND: Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power. RESULTS: Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation. CONCLUSIONS: Our findings support the use of BoostMe as a preprocessing step for WGBS analysis. PMID- 29792183 TI - Estimated intraoperative blood loss correlates with postoperative cardiopulmonary complications and length of stay in patients undergoing video-assisted thoracoscopic lung cancer lobectomy: a retrospective cohort study. AB - BACKGROUND: The purpose of our study was to estimate the influence of estimated intraoperative blood loss (EIBL) on postoperative cardiopulmonary complications (PCCs) in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: We conducted a single center retrospective analysis on the clinical data of consecutive patients in our institution between April 2015 and February 2016. Demographic differences between PCC group and non-PCC group were initially assessed. Receiver operating characteristic (ROC) analysis was performed to determine the threshold value of EIBL for the prediction of PCCs. Demographic differences in the PCC rates and length of stay between two groups of patients divided by this cutoff were further evaluated. A multivariable logistic-regression model involving the clinicopathological parameters with P-value< 0.05 was finally established to identify independent risk factors for PCCs. RESULTS: A total of 429 patients with operable NSCLC were included and 80 of them developed PCCs (rate = 18.6%). The mean EIBL in PCC group was significantly higher than that in non-PCC group (133.3 +/- 191.3 vs. 79.1 +/- 107.1 mL; P < 0.001). The ROC analysis showed an EIBL of 100 mL as the threshold value at which the joint sensitivity (50.0%) and specificity (73.4%) was maximal. The PCC rate in patients with EIBL>=100 mL was significantly higher than that in patients with EIBL< 100 mL (30.1 vs. 13.5%; P < 0.001). Both the length of stay and chest tube duration were significantly prolonged in the patients with EIBL>=100 mL. Finally, EIBL>=100 mL was identified to be predictive of PCCs by multivariable logistic-regression analysis (odds ratio = 3.01; 95% confidence interval = 1.47-6.16; P = 0.003). CONCLUSIONS: EIBL serves as a significant categorical predictor for cardiopulmonary complications following VATS lobectomy for NSCLC. Thoracic surgeons should minimize the EIBL and strive for the 'bloodless' goal to optimize surgical outcomes. PMID- 29792184 TI - Knowledge of orthodontic tooth movement through the maxillary sinus: a systematic review. AB - BACKGROUND: To investigate the feasibility, safety and stability of current interventions for moving teeth through the maxillary sinus (MTTMS) by performing a systematic review of the literature. METHODS: The electronic databases PubMed, Embase, CENTRAL, Web of Science, CBM, CNKI and SIGLE were searched without a language restriction. The primary outcomes were parameters related to orthodontic treatment, including orthodontic protocols, magnitude of forces, type of tooth movement, duration and rate of tooth movement, and remolding of alveolar bone and the maxillary sinus floor. The secondary outcomes were safety and stability, including root resorption, perforation of the sinus floor, loss of pulp vitality and periodontal health and relapse. RESULTS: Nine case reports with 25 teeth were included and systematically analyzed. Fifty to two hundred g of force was applied to move teeth through the maxillary sinus. Bodily movement was accomplished, but initial tipping was observed in 7 cases. The rate was 0.6-0.7 mm/month for molar intrusion and 0.16-1.17 and 0.05-0.16 mm/month for mesial-distal movement of premolars and molars, respectively. Bone formation and remolding of the sinus floor occurred in 7 cases. Root resorption within 6 to 30 months was observed in 3 cases, while no cases of perforation of the sinus floor, loss of pulp vitality, periodontal health impairment or relapse were reported. CONCLUSIONS: At the present stage, no evidence-based protocol could be recommended to guide MTTMS. The empirical application of constant and light to moderate forces (by TAD, segment and multibrackets) to slowly move teeth through or into the maxillary sinus in adults appears to be practical and secure. Bodily movement was accomplished, but teeth appear to be easily tipped initially, potentially resulting in root resorption. However, this conclusion should be interpreted with caution as the currently available evidence is based on only a few case reports or case series and longitudinal or controlled studies are lacking in this area. PMID- 29792185 TI - Assessment of the use of contrast enhanced ultrasound in guiding microdissection testicular sperm extraction in nonobstructive azoospermia. AB - BACKGROUND: The aim of this study is to assess the value of contrast-enhanced ultrasound (CEUS) as a new non-invasive approach to locate the testicular area in which spermatogenesis is most likely to be found in non-obstructive azoospermic testes and to evaluate the accuracy of CEUS as a predictor of successful sperm retrieval. METHODS: CEUS was performed in 120 nonobstructive azoospermia (NOA) patients. Microdissection testicular sperm extraction (M-TESE) was performed on the best and poorest perfusion areas selected by CEUS and on conventional areas. RESULTS: In the 187 testicles that underwent M-TESE, the sperm retrieval rates (SRRs) in the best perfusion area and poorest perfusion area over the maximal longitudinal section and conventional area were 63.1, 34.7 and 47.1%. According to receiver operating characteristic (ROC) analysis, the arrival times (AT) <=27 s, time-to-peak intensity (TTP) <=45 s, and peak intensity (PI) >=11 dB were the best predictors of positive sperm retrieval. The location of the best perfusion area was able to guide M-TESE to improve the success rates. CONCLUSIONS: Testicle CEUS is suggested to be performed in all patients with NOA. If AT<=27 s, TTP <= 45 s or PI>=11 dB are found in the best perfusion area, M-TESE is strongly recommended. PMID- 29792186 TI - Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell carcinoma. AB - BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH 133 and WIN 55,212-2 (WIN-55)] in RCC cell lines. METHODS: Human RCC cell lines were used for this study. The CB 1 and CB 2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB1 and CB2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells. RESULTS: The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis. CONCLUSIONS: This study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed. PMID- 29792187 TI - Carbonic anhydrase related protein expression in astrocytomas and oligodendroglial tumors. AB - BACKGROUND: Carbonic anhydrase related proteins (CARPs) VIII, X and XI functionally differ from the other carbonic anhydrase (CA) enzymes. Structurally, they lack the zinc binding residues, which are important for enzyme activity of classical CAs. The distribution pattern of the CARPs in fetal brain implies their role in brain development. In the adult brain, CARPs are mainly expressed in the neuron bodies but only weaker reactivity has been found in the astrocytes and oligodendrocytes. Altered expression patterns of CARPs VIII and XI have been linked to cancers outside the central nervous system. There are no reports on CARPs in human astrocytomas or oligodendroglial tumors. We wanted to assess the expression of CARPs VIII and XI in these tumors and study their association to different clinicopathological features and tumor-associated CAs II, IX and XII. METHODS: The tumor material for this study was obtained from surgical patients treated at the Tampere University Hospital in 1983-2009. CARP VIII staining was analyzed in 391 grade I-IV gliomas and CARP XI in 405 gliomas. RESULTS: CARP VIII immunopositivity was observed in 13% of the astrocytomas and in 9% of the oligodendrogliomas. Positive CARP XI immunostaining was observed in 7% of the astrocytic and in 1% of the oligodendroglial tumor specimens. In our study, the most benign tumors, pilocytic astrocytomas, did not express CARPs at all. In WHO grade II-IV astrocytomas, CARPs were associated with molecular events related to more benign behavior, which was the case with CARP VIII in oligodendrogliomas and oligoastrocytomas as well. CONCLUSIONS: The study observations suggest that the CARPs play a role in tumorigenesis of diffusively infiltrating gliomas. Furthermore, the molecular mechanisms beneath the cancer promoting qualities of CARPs have not yet been discovered. Thus, more studies concerning role of CARPs in oncogenesis are needed. PMID- 29792188 TI - Health-related quality of life in multiple sclerosis: temperament outweighs EDSS. AB - BACKGROUND: The influence of personality on health-related quality of life in patients with multiple sclerosis has been the focus of previous studies showing that introversion and neuroticism were related with reduced health related quality of life. However, no data exist on the impact of temperament on quality of life in this patient group. METHODS: Between April 2014 and March 2016 139 multiple sclerosis patients were recruited from a specialized outpatient clinic of the general hospital of Vienna. Health-related quality of life was measured by "The Multiple Sclerosis International Quality of Life Questionnaire (MusiQol)", temperament by "Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Questionnaire - Munster version" (briefTEMPS-M), and disability by the "Expanded disability status scale". All patients underwent a diagnostic psychiatric semi structured interview (MINI). RESULTS: Known predictors (like disease duration, EDSS, psychiatric co-morbidities, immunomodulatory treatments) explain the proportion of variation in the outcome of MusiQol global index score in 30.9% in multi-variable linear regression analysis. It increased respectively to 40.3, 42.5, and 45.8% if adding the depressive, cyclothymic, or hyperthymic temperament to the list of variables. An increase of depressive and cyclothymic temperament scores significantly reduced global index score of MusiQol (p = 0.005, p = 0.002, respectively), while the hyperthymic temperament significantly raised it (p < 0.001). CONCLUSION: In MS patients, the depressive and cyclothymic temperament predict a lower and hyperthymic temperament an increased health-related quality of life, independent of current disability status, immunomodulatory treatments, and affective co-morbidities. PMID- 29792189 TI - A cross-sectional ecological analysis of international and sub-national health inequalities in commercial geospatial resource availability. AB - BACKGROUND: Commercial geospatial data resources are frequently used to understand healthcare utilisation. Although there is widespread evidence of a digital divide for other digital resources and infra-structure, it is unclear how commercial geospatial data resources are distributed relative to health need. METHODS: To examine the distribution of commercial geospatial data resources relative to health needs, we assembled coverage and quality metrics for commercial geocoding, neighbourhood characterisation, and travel time calculation resources for 183 countries. We developed a country-level, composite index of commercial geospatial data quality/availability and examined its distribution relative to age-standardised all-cause and cause specific (for three main causes of death) mortality using two inequality metrics, the slope index of inequality and relative concentration index. In two sub-national case studies, we also examined geocoding success rates versus area deprivation by district in Eastern Region, Ghana and Lagos State, Nigeria. RESULTS: Internationally, commercial geospatial data resources were inversely related to all-cause mortality. This relationship was more pronounced when examining mortality due to communicable diseases. Commercial geospatial data resources for calculating patient travel times were more equitably distributed relative to health need than resources for characterising neighbourhoods or geocoding patient addresses. Countries such as South Africa have comparatively high commercial geospatial data availability despite high mortality, whilst countries such as South Korea have comparatively low data availability and low mortality. Sub-nationally, evidence was mixed as to whether geocoding success was lowest in more deprived districts. CONCLUSIONS: To our knowledge, this is the first global analysis of commercial geospatial data resources in relation to health outcomes. In countries such as South Africa where there is high mortality but also comparatively rich commercial geospatial data, these data resources are a potential resource for examining healthcare utilisation that requires further evaluation. In countries such as Sierra Leone where there is high mortality but minimal commercial geospatial data, alternative approaches such as open data use are needed in quantifying patient travel times, geocoding patient addresses, and characterising patients' neighbourhoods. PMID- 29792190 TI - Novel insights into neuroinflammation: bacterial lipopolysaccharide, tumor necrosis factor alpha, and Ureaplasma species differentially modulate atypical chemokine receptor 3 responses in human brain microvascular endothelial cells. AB - BACKGROUND: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.). Although commonly regarded as commensals of the adult urogenital tract, Ureaplasma spp. may cause invasive infections in immunocompromised adults as well as in neonates and appear to be relevant pathogens in neonatal meningitis. Nonetheless, clinical and in vitro data on Ureaplasma-induced inflammation are scarce. METHODS: We established a cell culture model of Ureaplasma meningitis, aiming to analyze ACKR3 variances as a possible pathomechanism in Ureaplasma-associated neuroinflammation. Non immortalized human brain microvascular endothelial cells (HBMEC) were exposed to bacterial lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), and native as well as LPS-primed HBMEC were cultured with Ureaplasma urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). ACKR3 responses were assessed via qRT-PCR, RNA sequencing, flow cytometry, and immunocytochemistry. RESULTS: LPS, TNF-alpha, and Ureaplasma spp. influenced ACKR3 expression in HBMEC. LPS and TNF alpha significantly induced ACKR3 mRNA expression (p < 0.001, vs. control), whereas Ureaplasma spp. enhanced ACKR3 protein expression in HBMEC (p < 0.01, vs. broth control). Co-stimulation with LPS and either Ureaplasma isolate intensified ACKR3 responses (p < 0.05, vs. LPS). Furthermore, stimulation wielded a differential influence on the receptor's ligands. CONCLUSIONS: We introduce an in vitro model of Ureaplasma meningitis. We are able to demonstrate a pro inflammatory capacity of Ureaplasma spp. in native and, even more so, in LPS primed HBMEC, underlining their clinical relevance particularly in a setting of co-infection. Furthermore, our data may indicate a novel role for ACKR3, with an impact not limited to auto-inflammatory diseases, but extending to infection related neuroinflammation as well. AKCR3-induced blood-brain barrier breakdown might constitute a potential common pathomechanism. PMID- 29792191 TI - Cost of provision of opioid substitution therapy provision in Tijuana, Mexico. AB - BACKGROUND: Mexico recently enacted drug policy reform to decriminalize possession of small amounts of illicit drugs and mandated that police refer identified substance users to drug treatment. However, the economic implications of drug treatment expansion are uncertain. We estimated the costs of opioid substitution therapy (OST) provision in Tijuana, Mexico, where opioid use and HIV are major public health concerns. METHODS: We adopted an economic health care provider perspective and applied an ingredients-based micro-costing approach to quantify the average monthly cost of OST (methadone maintenance) provision at two providers (one private and one public) in Tijuana, Mexico. Costs were divided by type of input (capital, recurrent personnel and non-personnel). We defined "delivery cost" as all costs except for the methadone and compared total cost by type of methadone (powdered form or capsule). Cost data were obtained from interviews with senior staff and review of expenditure reports. Service provision data were obtained from activity logs and senior staff interviews. Outcomes were cost per OST contact and cost per person month of OST. We additionally collected information on patient charges for OST provision from published rates. RESULTS: The total cost per OST contact at the private and public sites was $3.12 and $5.90, respectively, corresponding to $95 and $179 per person month of OST. The costs of methadone delivery per OST contact were similar at both sites ($2.78 private and $3.46 public). However, cost of the methadone itself varied substantially ($0.34 per 80 mg dose [powder] at the private site and $2.44 per dose [capsule] at the public site). Patients were charged $1.93-$2.66 per methadone dose. CONCLUSIONS: The cost of OST provision in Mexico is consistent with other upper-middle income settings. However, evidenced-based (OST) drug treatment facilities in Mexico are still unaffordable to most people who inject drugs. PMID- 29792193 TI - Research ethics review at University Eduardo Mondlane (UEM)/Maputo Central Hospital, Mozambique (2013-2016): a descriptive analysis of the start-up of a new research ethics committee (REC). AB - BACKGROUND: Mozambique has seen remarkable growth in biomedical research over the last decade. To meet a growing need, the National Committee for Bioethics in Health of Mozambique (CNBS) encouraged the development of ethical review processes at institutions that regularly conduct medical and social science research. In 2012, the Faculty of Medicine (FM) of University Eduardo Mondlane (UEM) and the Maputo Central Hospital (MCH) established a joint Institutional Committee on Bioethics for Health (CIBS FM & MCH). This study examines the experience of the first 4 years of the CIBS FM & MCH. METHODS: This study provides a descriptive, retrospective analysis of research protocols submitted to and approved by the CIBS FM & MCH between March 1, 2013 and December 31, 2016, together with an analysis of the Committee's respective reviews and actions. RESULTS: A total of 356 protocols were submitted for review during the period under analysis, with 309 protocols approved. Sixty-four percent were submitted by students, faculty, and researchers from UEM, mainly related to Master's degree research (42%). Descriptive cross-sectional studies were the most frequently reviewed research (61%). The majority were prospective (71%) and used quantitative methodologies (51%). The Departments of Internal Medicine at MCH and Community Health at the FM submitted the most protocols from their respective institutions, with 38 and 53% respectively. The CIBS's average time to final approval for all protocols was 56 days, rising to 161 for the 40 protocols that required subsequent national-level review by the CNBS. CONCLUSIONS: Our results show that over its first 4 years, the CIBS FM & MCH has been successful in managing a constant demand for protocol review and that several broad quality improvement initiatives, such as investigator mentoring and an electronic protocol submission platform have improved efficiency in the review process and the overall quality of the protocols submitted. Beyond Maputo, long-term investments in training and ethical capacity building for CIBS across the country continue to be needed, as Mozambique develops greater capacity for research and makes progress toward improving the health of all its citizens. PMID- 29792194 TI - Comparison of aqueous, polyethylene glycol-aqueous and ethanolic propolis extracts: antioxidant and mitochondria modulating properties. AB - BACKGROUND: Propolis is multicomponent substance collected by honeybees from various plants. It is known for numerous biological effects and is commonly used as ethanolic extract because most of active substances of propolis are ethanol soluble. However, water-based propolis extracts could be applied more safely, as this solvent is more biocompatible. On the other hand, water extracts has significantly smaller range and quantity of active compounds. The extraction power of water could be enhanced by adding co-solvent which increases both solubility and penetration of propolis compounds. However, variation of solvents results in different composition of active substances that might have distinct effects. The majority of biological effects of propolis are attributed to the antioxidant properties of its active compounds. Antioxidant effect might be a result of either direct scavenging of ROS or modulation of ROS producing organelle activity. Therefore, the aim of this study was to investigate and compare chemical composition, antioxidant properties and effects on mitochondrial respiration of aqueous (AqEP), polyethylene glycol-aqueous (Pg-AqEP) and ethanolic (EEP) propolis extracts. METHODS: Chemical composition of propolis extracts was determined using HPLC and Folin-Ciocalteu method. Ability to neutralize H2O2 and intracellular ROS concentration in C6 glioma cells were determined fluorometrically by using 10-acetyl-3,7-dihydroxyphenoxazine and 2',7' dichlorofluorescein diacetate, respectively. Mitochondrial superoxide generation was assessed under fluorescent microscope by using MitoSOX Red. Oxygen uptake rates of mitochondria were recorded by high-resolution respirometer Oxygraph-2 k. RESULTS: Our data revealed that phenolic acids and aldehydes make up 40-42% of all extracted and identified compounds in AqEP and Pg-AqEP and only 16% in EEP. All preparations revealed similar antioxidant activity in cell culture medium but Pg-AqEP and EEP demonstrated better mitochondrial superoxide and total intracellular ROS decreasing properties. At higher concentrations, AqEP and EEP inhibited mitochondrial respiration, but Pg-AqEP had concentration-dependent mitochondria-uncoupling effect. CONCLUSIONS: Aqueous and non-aqueous propolis extracts differ by composition, but all of them possess antioxidant properties and neutralize H2O2 in solution at similar efficiency. However, both Pg-AqEP and EEP were more effective in decreasing intracellular and intramitochondrial ROS compared to AqEP. At higher concentrations, these preparations affect mitochondrial functions and change energy production in C6 cells. PMID- 29792192 TI - Detection technologies and metabolic profiling of bile acids: a comprehensive review. AB - Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely associated with intestinal hormones, microbiotas and energy balance. BAs abnormalities easily lead to inflammation and metabolic diseases, in turn, the progress of diseases could influence characteristics of BAs. Therefore, accurate detection of BAs contents is of great significance to disease prevention, diagnosis and treatment. At present, the most widely used enzymatic method in clinical practice is applicable to the detection of total bile acid (TBA). In laboratory research, different types of BAs can be accurately separated and quantified by liquid chromatography-mass spectrometry (LC-MS). The metabolic profiling of BAs based on detection technologies can completely and accurately monitor their types and contents, playing a crucial role in disease prevention, diagnosis and treatment. We herein reviewed the main detection technologies of BAs and the application of metabolic profiling in related diseases in recent years. PMID- 29792196 TI - Ethnozoological study of traditional medicinal appreciation of animals and their products among the indigenous people of Metema Woreda, North-Western Ethiopia. AB - BACKGROUND: Using animals for different purposes goes back to the dawn of mankind. Animals served as a source of food, medicine, and clothing for humans and provided other services. This study was designed to undertake a cross sectional ethnozoological field survey among the residents of Metema Woreda from November 2015 to May 2016. METHODS: Data were collected through studied questionnaires, interviews, and focus group discussions with 36 purposively selected respondents. RESULTS: Ethnozoological data were collected of the local name of the animals, part of the animal used, mode of preparation and administration, and of additional information deemed useful. A total of 51 animal species were identified to treat around 36 different ailments. Of the animals used therapeutically, 27 species were mammals, 9 were birds, 7 arthropods, 6 reptiles, and 1 species each represented fish and annelids. Furthermore, the honey of the bee Apis mellifera was used to relieve many ailments and scored the highest fidelity value (n = 35.97%). The snake (Naja naja) and the teeth of crocodiles (Crocodylus spp.) had the lowest fidelity value (n = 2.56%). CONCLUSION: The results show that there is a wealth of ethnozoological knowledge to be documented which could be of use in developing new drugs. Hence, it is hoped that the information contained in this paper will be useful in future ethnozoological, ethnopharmacological, and conservation-related research of the region. PMID- 29792195 TI - Histamine activates inflammatory response and depresses casein synthesis in mammary gland of dairy cows during SARA. AB - BACKGROUND: Mounting evidences observed that subacute ruminal acidosis (SARA) induced by high concentration (HC) diet increases the translocation of histamine from digestive tract into circulation causing a diverse of diseases in dairy cows. However, it is largely unknown how it does affect the function of mammary gland and milk quality. Hence, this study aims to observe the effects of histamine derived from the digestive tract on the inflammatory response and casein synthesis in the mammary glands during SARA. Twelve cows fitted rumen fistula were randomly divided into either control group administrated low concentration (LC) diet (60% forage, n = 6) or treatment group administrated HC diet (40% forage, n = 6) for 18 weeks. RESULTS: Our data showed that HC diet resulted in significant declines in rumen pH value, milk yield and milk quality, as well as longer duration of averaged pH value below 5.6 per day (more than 180 min) compared to LC diet, these findings confirmed SARA occurence. Our study also observed that SARA increased the content of histamine in rumen fluid, plasma, liver and mammary gland, and enhanced the mRNA expression of histamine specific receptor in the mammary gland. Additionally, we found that the mRNA expression of inflammatory response genes in mammary glands was increased, which was consistent with the protein expression results, showing that the protein kinase C(PKC) / nuclear factor kappa B (NF-kappaB) or protein kinase A (PKA) / NF-kappaB signalling pathways of the inflammatory response were activated. The mRNA expression of mTOR, P70S6K and alphaS1 in mammary glands were significantly decreased with the protein expression of mTOR, P70S6K and alphaS1-casein, and the phosphorylation levels of the mTOR and P70S6K proteins were also decreased. CONCLUSIONS: Our study showed that the milk protein of lactating cows is depressed after long-term feeding of HC at the individual level, which was paralleled at the gene and protein levels. The inflammatory response in mammary gland caused by histamine derived from the digestive tract is related to the decline of casein synthesis. Our findings point to a new link between the inflammatory response and casein synthesis, but the understanding of the molecular mechanisms involved in this process will require further research. PMID- 29792197 TI - Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli: comparison between Etest and a broth dilution method. AB - BACKGROUND: Campylobacter is a leading cause of foodborne gasteroenteritis worldwide. Antimicrobial susceptibility testing for Campylobacter spp. is not routinely performed by most clinical laboratories. However, the emergence of resistant isolates strengthens the importance of antimicrobial susceptibility testing and the critical need for epidemiologic surveillance. The aim of this study was to compare the efficacy of Etest and Sensititre kit (a broth microdilution method) as methods for susceptibility tests and the critical need for epidemiologic surveillance. The aim of this study was to compare the efficacy of Etest and Sensititre kit (a broth microdilution method) as methods for susceptibility testing of Campylobacter spp. to tetracycline, erythromycin, and ciprofloxacin. METHODS: Sixty-six Campylobacter isolates were collected from feces samples and subjected to susceptibility testing by Etest and Sensititre, a broth microdilution kit for tetracycline, erythromycin, and ciprofloxacin. Minimal inhibitory concentration (MIC) results of each method were determined and compared. RESULTS: Similar MIC interpretations for tetracycline, erythromycin, and ciprofloxacin were found in 97%, 98.5%, and 100% of the isolates, respectively, indicating a good level of agreement between Etest and Sensititre (p < 0.0001); additionally, the correlation between the two methods was highly significant for the three tested antibiotics (p < 0.0001). CONCLUSIONS: Both the broth microdilution and the Etest are reliable and convenient methods for testing antimicrobial susceptibility of Campylobacter spp. The Sensititre kit has the advantages of high availability and the automation. PMID- 29792198 TI - Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches. AB - Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy. PMID- 29792199 TI - Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation. AB - BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS: Plain, 6 coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-kappaB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS: Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 degrees C in Simulated Lung Fluid up to 48 h and at 4 degrees C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-kappaB nuclear translocation. CONCLUSIONS: SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases. PMID- 29792200 TI - Wedge-shaped microfluidic chip for circulating tumor cells isolation and its clinical significance in gastric cancer. AB - BACKGROUND: Circulating tumor cells (CTCs) have great potential in both basic research and clinical application for the managements of cancer. However, the complicated fabrication processes and expensive materials of the existing CTCs isolation devices, to a large extent, limit their clinical translation and CTCs' clinical value. Therefore, it remains to be urgently needed to develop a new platform for achieving CTCs detection with low-cost, mass-producible but high performance. METHODS: In the present study, we introduced a novel wedge-shaped microfluidic chip (named CTC-DeltaChip) fabricated by two pieces of glass through wet etching and thermal bonding technique for CTCs isolation, which achieved CTCs enrichment by different size without cell surface expression markers and CTCs identification with three-color immunocytochemistry method (CK+/CD45-/Nucleus+). We validated the feasibility of CTC-DeltaChip for detecting CTCs from different types of solid tumor. Furthermore, we applied the newly-developed platform to investigate the clinical significance of CTCs in gastric cancer (GC). RESULTS: Based on "label-free" characteristic, the capture efficiency of CTC-DeltaChip can be as high as 93.7 +/- 3.2% in DMEM and 91.0 +/- 3.0% in whole blood sample under optimized conditions. Clinically, CTC-DeltaChip exhibited the feasibility of detecting CTCs from different types of solid tumor, and it identified 7.30 +/- 7.29 CTCs from 2 mL peripheral blood with a positive rate of 75% (30/40) in GC patients. Interestingly, we found that GC CTCs count was significantly correlated with multiple systemic inflammation indexes, including the lymphocyte count, platelet count, the level of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. In addition, we also found that both the positivity rate and CTCs count were significantly associated with multiple clinicopathology parameters. CONCLUSIONS: Our novel CTC-DeltaChip shows high performance for detecting CTCs from less volume of blood samples of cancer patients and important clinical significance in GC. Owing to the advantages of low-cost and mass producible, CTC-DeltaChip holds great potential of clinical application for cancer therapeutic guidance and prognostic monitoring in the future. PMID- 29792202 TI - The effects of a lifestyle-focused text-messaging intervention on adherence to dietary guideline recommendations in patients with coronary heart disease: an analysis of the TEXT ME study. AB - BACKGROUND: A healthy diet is an important component of secondary prevention of coronary heart disease (CHD). The TEXT ME study was a randomised clinical trial of people with CHD that were randomised into standard care or a text-message programme in addition to standard care. This analysis aimed to: 1) assess the effects of the intervention onadherence to the dietary guideline recommendations; 2) assess the consistency of effect across sub-groups; and 3) assess whether adherence to the dietary guideline recommendations mediated the improvements in objective clinical outcomes. METHODS: Dietary data were collected using a self report questionnaire to evaluate adherence to eight dietary guideline recommendations in Australia, including consumption of vegetables, fruits, fish, type of fat used for cooking and in spreads, takeaway food, salt and standard alcohol drinks. The primary outcome of this analysis was the proportion of patients adhering to >= 4 dietary guideline recommendations concomitantly and each recommendation was assessed individually as secondary outcomes. Data were analysed using log-binomial regression for categorical variables and analysis of covariance for continuous variables. RESULTS: Among 710 patients, 54% were adhering to >= 4 dietary guideline recommendations (intervention 53% vs control 56%, p = 0.376) at baseline. At six months, the intervention group had a significantly higher proportion of patients adhering to >= 4 recommendations (314, 93%) compared to the control group (264, 75%, RR 1.23, 95% CI 1.15-1.31, p < 0.001). In addition, the intervention patients reported consuming higher amounts of vegetables, fruits, and fish per week; less takeaway foods per week; and greater salt intake control. The intervention had a similar effect in all sub groups tested. There were significant mediational effects of the increase in adherence to the recommendations for the association between the intervention and LDL-cholesterol (p < 0.001) and body mass index (BMI) at six months follow-up (p = 0.005). CONCLUSION: A lifestyle-focused text-message programme improved adherence to the dietary guideline recommendations, and specifically improved self-reported consumption of vegetables, fruits, fish, takeaway foods and salt intake. Importantly, these improvements partially mediated improvements in LDL cholesterol and BMI. This simple and scalable text-messaging intervention could be used as a strategy to improve diet in people with CHD. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12611000161921 . Registered on 10 February 2011. PMID- 29792201 TI - Cerium dioxide nanoparticles exacerbate house dust mite induced type II airway inflammation. AB - BACKGROUND: Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2NPs in a house dust mite (HDM) induced murine model of asthma. RESULTS: Repeated intranasal instillation of CeO2NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia. This was accompanied by increases in IL-4, CCL11 and MCPT1 gene expression together with increases in the mucin and inflammatory regulators CLCA1 and SLC26A4. CLCA1 and SLC26A4 were also induced by CeO2NPs + HDM co-exposure in air liquid interface cultures of human primary bronchial epithelial cells. HDM induced airway hyperresponsiveness and airway remodelling in mice were not altered with CeO2NPs co-exposure. Repeated HMD instillations followed by a single exposure to CeO2NPs failed to produce changes in type II inflammatory endpoints but did result in alterations in the neutrophil marker CD177. Treatment of mice with CeO2NPs in the absence of HDM did not have any significant effects. RNA-SEQ was used to explore early effects 24 h after single treatment exposures. Changes in SAA3 expression paralleled increased neutrophil BAL levels, while no changes in eosinophil or lymphocyte levels were observed. HDM resulted in a strong induction of type I interferon and IRF3 dependent gene expression, which was inhibited with CeO2NPs co-exposure. Changes in the expression of genes including CCL20, CXCL10, NLRC5, IRF7 and CLEC10A suggest regulation of dendritic cells, macrophage functionality and IRF3 modulation as key early events in how CeO2NPs may guide pulmonary responses to HDM towards type II inflammation. CONCLUSIONS: CeO2NPs were observed to modulate the murine pulmonary response to house dust mite allergen exposure towards a type II inflammatory environment. As this type of response is present within asthmatic endotypes this finding may have implications for how occupational or incidental exposure to CeO2NPs should be considered for those susceptible to disease. PMID- 29792203 TI - Short-term outcomes of robot-assisted minimally invasive esophagectomy for esophageal cancer: a propensity score matched analysis. AB - BACKGROUND: Minimally invasive esophagectomy (MIE) was shown to be effective in reducing the morbidity and was adopted increasingly. The robot-assisted minimally invasive esophagectomy (RAMIE) remains in the initial stage of application. This study evaluated its safety and feasibility by comparing short-term outcomes of RAMIE and video-assisted minimally invasive esophagectomy (VAMIE). METHODS: Between March 2016 and December 2017, 115 consecutive patients underwent RAMIE or VAMIE at our institute. The baseline characteristics, pathological data and short term outcomes of these two group patients were collected and compared. RAMIE patients were propensity score matched with VAMIE patients for a more accurate comparison. RESULTS: Matching based on propensity scores produced 27 patients in each group. After propensity score matching (PSM), the baseline characteristics between the two groups were comparable. The operation time in RAMIE group was significantly longer than that in VAMIE group (349 and 294 min, respectively; P < 0.001). The blood loss volume in RAMIE group was less than that in VAMIE group (119 and 158 ml, respectively), but with no statistically significant difference (P = 0.062). There was no significant difference between the two groups with respect to the mean number of dissected lymph nodes (20 and 19, respectively; P = 0.420), postoperative hospital stay (13.8 and 12.7 days, respectively; P = 0.548), the rate of overall complications (37.0 and 33.3%, respectively; P = 0.776) and the rates of detailed complications between the two groups. CONCLUSIONS: The short-term outcomes of RAMIE is comparable to VAMIE, demonstrating safety and feasibility of RAMIE. PMID- 29792204 TI - The evolution of the field of Health Policy and Systems Research and outstanding challenges. AB - BACKGROUND: We provide a historical analysis of the evolution of the field of health policy and systems research (HPSR) since 1996. In the mid-1990s, three main challenges affected HPSR, namely (1) fragmentation and lack of a single agreed definition of the field; (2) ongoing dominance of biomedical and clinical research; and (3) lack of demand for HPSR. Cross-cutting all these challenges was the problem of relatively limited capacity to undertake high quality HPSR. Our discussion analyses how these problems were addressed so as to facilitate growth and enhanced recognition of the field. DISCUSSION: HPSR has benefitted significantly from increased recognition of the importance of strong health systems to health outcomes, particularly those linked to the Millennium Development Goals. In addition to this, some of the challenges described above have been addressed through (1) sustained advocacy for the importance of HPSR, (2) efforts to clarify the content and focus of the field, and (3) growing appreciation of and efforts to engage health practitioners and policy-makers in HPSR. While advocacy for the field of HPSR was initially fragmented, since the late 1990s there has been a consistent flow of focusing events and publications that have served to enhance the profile and understanding of the field. There have also been multiple efforts to establish greater coherence within the field, for example, interrogating the distinctions between health services research and health systems research, and how critical the "P" for policy is to HPSR. Finally, HPSR has developed at the same time as growing interest in evidence-informed policy and, more recently, implementation science, which have served to underscore the relevance and utility of HPSR to policy- and decision-makers. CONCLUSIONS: During the past two decades, the field of HPSR has developed significantly, leading to enhanced clarity about its purpose, activity levels and utility. Several challenges remain that will need to be addressed in the decades ahead. PMID- 29792205 TI - Distinct correlations between lipogenic gene expression and fatty acid composition of subcutaneous fat among cattle breeds. AB - BACKGROUND: The fatty acid (FA) composition of adipose tissue influences the nutritional quality of meat products. The unsaturation level of FAs is determined by fatty acid desaturases such as stearoyl-CoA desaturases (SCDs), which are under control of the transcription factor sterol regulatory element-binding protein (SREBP). Differences in SCD genotype may thus confer variations in lipid metabolism and FA content among cattle breeds. This study investigated correlations between FA composition and lipogenic gene expression levels in the subcutaneous adipose tissue of beef cattle breeds of different gender from the Basque region of northern Spain. Pirenaica is the most important beef cattle breed in northern Spain, while Salers cattle and Holstein-Friesian cull cows are also an integral part of the regional beef supply. RESULTS: Pirenaica heifers showed higher monounsaturated FA (MUFA) and conjugated linoleic acid (CLA) contents in subcutaneous adipose tissue than other breeds (P < 0.001). Alternatively, Salers bulls produced the highest oleic acid content, followed by Pirenaica heifers (P < 0.001). There was substantial variability in SCD gene expression among breeds, consistent with these differences in MUFA and CLA content. Correlations between SCD1 expression and most FA desaturation indexes (DIs) were positive in Salers (P < 0.05) and Pirenaica bulls, while, in general, SCD5 expression showed few significant correlations with DIs. There was a significant linear correlation between SCD1 and SRBEP1 in all breeds, suggesting strong regulation of SCD1 expression by SRBEP1. Pirenaica heifers showed a stronger correlation between SCD1 and SREBP1 than Pirenaica bulls. We also observed a opposite relationship between SCD1 and SCD5 expression levels and opposite associations of isoform expression levels with the ?9 desaturation indexes. CONCLUSIONS: These results suggest that the relationships between FA composition and lipogenic gene expression are influenced by breed and sex. The opposite relationship between SCD isoforms suggests a compensatory regulation of total SCD activity, while opposite relationships between SCD isoforms and desaturation indexes, specially 9c-14:1 DI, previously reported as an indicator of SCD activity, may reflect distinct activities of SCD1 and SCD5 in regulation of FA content. These findings may be useful for beef/dairy breeding and feeding programs to supply nutritionally favorable products. PMID- 29792206 TI - Is the cup orientation different in bilateral total hip arthroplasty with right handed surgeons using posterolateral approach? AB - BACKGROUND: The impact of surgeon handedness on acetabular cup orientation in total hip arthroplasty (THA) is not well studied. The aim of our study is to investigate the difference of cup orientation in bilateral THA performed by right handed surgeons using posterolateral approach and which cup could be fitter to Lewinneck's safe zone. METHODS: The study consisted of 498 patients that underwent bilateral THA by three right-handed surgeons in our hospital. Postoperative acetabular cup anteversion and abduction on an anteroposterior pelvic radiograph were measured by Orthoview software (Orthoview LLC, Jacksonville, Florida). Furthermore, the percentage of cup placement within the safe zone was compared. RESULTS: The mean anteversion was 25.28 (25.28 degrees +/- 7.16 degrees ) in left THA and 22.01 (22.01 degrees +/- 6.35 degrees ) in right THA (p < 0.001). The mean abduction was 37.50 (37.50 degrees +/- 6.76 degrees ) in left THA and 38.59 (38.59 degrees +/- 6.84 degrees ) in right THA (p = 0.011). In the left side, the cup was positioned in Lewinnek's safe zone in 52% for anteversion, 87% for abduction, and 46% for both anteversion and abduction. But the cup placement within Lewinnek's safe zone was 71, 88, and 62% in the right side, respectively. There were significant differences in the percentage of acetabular cup placement within the safe zone for anteversion (p < 0.001) and for both anteversion and inclination (p < 0.001). Dislocation occurred in 7.0% (35/498) of cases in left THA and 3.2% (16/498) in right THA. The percentages of patients experiencing dislocation were significantly different between the two sides (p = 0.006). CONCLUSIONS: This current study demonstrated that surgeon handedness is likely to be a contributing factor that affects cup inclination and anteversion in bilateral THA and that the placement of cup performed by dominant hands of surgeons is more accurate than that performed by non-dominant sides. PMID- 29792208 TI - Automated chest screening based on a hybrid model of transfer learning and convolutional sparse denoising autoencoder. AB - OBJECTIVE: In this paper, we aim to investigate the effect of computer-aided triage system, which is implemented for the health checkup of lung lesions involving tens of thousands of chest X-rays (CXRs) that are required for diagnosis. Therefore, high accuracy of diagnosis by an automated system can reduce the radiologist's workload on scrutinizing the medical images. METHOD: We present a deep learning model in order to efficiently detect abnormal levels or identify normal levels during mass chest screening so as to obtain the probability confidence of the CXRs. Moreover, a convolutional sparse denoising autoencoder is designed to compute the reconstruction error. We employ four publicly available radiology datasets pertaining to CXRs, analyze their reports, and utilize their images for mining the correct disease level of the CXRs that are to be submitted to a computer aided triaging system. Based on our approach, we vote for the final decision from multi-classifiers to determine which three levels of the images (i.e. normal, abnormal, and uncertain cases) that the CXRs fall into. RESULTS: We only deal with the grade diagnosis for physical examination and propose multiple new metric indices. Combining predictors for classification by using the area under a receiver operating characteristic curve, we observe that the final decision is related to the threshold from reconstruction error and the probability value. Our method achieves promising results in terms of precision of 98.7 and 94.3% based on the normal and abnormal cases, respectively. CONCLUSION: The results achieved by the proposed framework show superiority in classifying the disease level with high accuracy. This can potentially save the radiologists time and effort, so as to allow them to focus on higher-level risk CXRs. PMID- 29792207 TI - Metagenomic analysis of viruses associated with maize lethal necrosis in Kenya. AB - BACKGROUND: Maize lethal necrosis is caused by a synergistic co-infection of Maize chlorotic mottle virus (MCMV) and a specific member of the Potyviridae, such as Sugarcane mosaic virus (SCMV), Wheat streak mosaic virus (WSMV) or Johnson grass mosaic virus (JGMV). Typical maize lethal necrosis symptoms include severe yellowing and leaf drying from the edges. In Kenya, we detected plants showing typical and atypical symptoms. Both groups of plants often tested negative for SCMV by ELISA. METHODS: We used next-generation sequencing to identify viruses associated to maize lethal necrosis in Kenya through a metagenomics analysis. Symptomatic and asymptomatic leaf samples were collected from maize and sorghum representing sixteen counties. RESULTS: Complete and partial genomes were assembled for MCMV, SCMV, Maize streak virus (MSV) and Maize yellow dwarf virus-RMV (MYDV-RMV). These four viruses (MCMV, SCMV, MSV and MYDV RMV) were found together in 30 of 68 samples. A geographic analysis showed that these viruses are widely distributed in Kenya. Phylogenetic analyses of nucleotide sequences showed that MCMV, MYDV-RMV and MSV are similar to isolates from East Africa and other parts of the world. Single nucleotide polymorphism, nucleotide and polyprotein sequence alignments identified three genetically distinct groups of SCMV in Kenya. Variation mapped to sequences at the border of NIb and the coat protein. Partial genome sequences were obtained for other four potyviruses and one polerovirus. CONCLUSION: Our results uncover the complexity of the maize lethal necrosis epidemic in Kenya. MCMV, SCMV, MSV and MYDV-RMV are widely distributed and infect both maize and sorghum. SCMV population in Kenya is diverse and consists of numerous strains that are genetically different to isolates from other parts of the world. Several potyviruses, and possibly poleroviruses, are also involved. PMID- 29792209 TI - Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study. AB - BACKGROUND: Discretionary screen time (time spent viewing a television or computer screen during leisure time) is an important contributor to total sedentary behaviour, which is associated with increased risk of mortality and cardiovascular disease (CVD). The aim of this study was to determine whether the associations of screen time with cardiovascular disease and all-cause mortality were modified by levels of cardiorespiratory fitness, grip strength or physical activity. METHODS: In total, 390,089 participants (54% women) from the UK Biobank were included in this study. All-cause mortality, CVD and cancer incidence and mortality were the main outcomes. Discretionary television (TV) viewing, personal computer (PC) screen time and overall screen time (TV + PC time) were the exposure variables. Grip strength, fitness and physical activity were treated as potential effect modifiers. RESULTS: Altogether, 7420 participants died, and there were 22,210 CVD events, over a median of 5.0 years follow-up (interquartile range 4.3 to 5.7; after exclusion of the first 2 years from baseline in the landmark analysis). All discretionary screen-time exposures were significantly associated with all health outcomes. The associations of overall discretionary screen time with all-cause mortality and incidence of CVD and cancer were strongest amongst participants in the lowest tertile for grip strength (all-cause mortality hazard ratio per 2-h increase in screen time (1.31 [95% confidence interval: 1.22-1.43], p < 0.0001; CVD 1.21 [1.13-1.30], p = 0.0001; cancer incidence 1.14 [1.10-1.19], p < 0.0001) and weakest amongst those in the highest grip-strength tertile (all-cause mortality 1.04 [0.95-1.14], p = 0.198; CVD 1.05 [0.99-1.11], p = 0.070; cancer 0.98 [0.93-1.05], p = 0.771). Similar trends were found for fitness (lowest fitness tertile: all-cause mortality 1.23 [1.13-1.34], p = 0.002 and CVD 1.10 [1.02-1.22], p = 0.010; highest fitness tertile: all-cause mortality 1.12 [0.96-1.28], p = 0.848 and CVD 1.01 [0.96-1.07], p = 0.570). Similar findings were found for physical activity for all-cause mortality and cancer incidence. CONCLUSIONS: The associations between discretionary screen time and adverse health outcomes were strongest in those with low grip strength, fitness and physical activity and markedly attenuated in those with the highest levels of grip strength, fitness and physical activity. Thus, if these associations are causal, the greatest benefits from health promotion interventions to reduce discretionary screen time may be seen in those with low levels of strength, fitness and physical activity. PMID- 29792210 TI - Quantitative cardiovascular magnetic resonance: extracellular volume, native T1 and 18F-FDG PET/CMR imaging in patients after revascularized myocardial infarction and association with markers of myocardial damage and systemic inflammation. AB - BACKGROUND: Characterization of tissue integrity and inflammatory processes after acute myocardial infarction (AMI) using non-invasive imaging is predictive of patient outcome. Quantitative cardiovascular magnetic resonance (CMR) techniques such as native T1 and extracellular volume (ECV) mapping as well as 18F-FDG positron emission tomography (PET) imaging targeting inflammatory cell populations are gaining acceptance, but are often applied without assessing their quantitative potential. Using simultaneously acquired PET/CMR data from patients early after AMI, this study quantitatively compares these three imaging markers and investigates links to blood markers of myocardial injury and systemic inflammatory activity. METHODS: A total of 25 patients without microvascular obstruction were retrospectively recruited. All imaging was simultaneously performed 5 +/- 1 days after revascularization following AMI on an integrated 3T PET/MRI scanner. Native and post-contrast T1 data were acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, ECV maps were calculated using individually sampled hematocrit. 18F-FDG PET was executed after 1 day of dietary preparation, 12 h of fasting, and administration of heparin. ECV, 18F-FDG and native T1 data were compared mutually as well as to peak counts of peripheral blood markers (creatine kinase, creatine kinase-MB, troponin, leukocytes, monocytes) and infarct size. RESULTS: High intra-patient correlations of relative ECV, 18F-FDG PET and native T1 signal increases were observed in combination with no inter-patient correlation of maximum absolute values at the infarct center, suggesting well-colocalized but physiologically diverse processes begetting the respective image signals. Comparison of maximum image signals to markers of myocardial damage and systemic inflammation yielded highly significant correlations of ECV to peak creatine kinase-MB and overall infarct size as well as between native T1 and peak monocyte counts. CONCLUSIONS: Absolute native T1 values at the infarct core early after AMI can be linked to the systemic inflammatory response independent of infarct size. Absolute ECV at the infarct core is related to both infarct size and blood markers of myocardial damage. PMID- 29792211 TI - The impact of ankle-foot orthoses on toe clearance strategy in hemiparetic gait: a cross-sectional study. AB - BACKGROUND: Ankle-foot orthoses (AFOs) are frequently used to improve gait stability, toe clearance, and gait efficiency in individuals with hemiparesis. During the swing phase, AFOs enhance lower limb advancement by facilitating the improvement of toe clearance and the reduction of compensatory movements. Clinical monitoring via kinematic analysis would further clarify the changes in biomechanical factors that lead to the beneficial effects of AFOs. The purpose of this study was to investigate the actual impact of AFOs on toe clearance, and determine the best strategy to achieve toe clearance (including compensatory movements) during the swing phase. METHODS: This study included 24 patients with hemiparesis due to stroke. The gait performance of these patients with and without AFOs was compared using three-dimensional treadmill gait analysis. A kinematic analysis of the paretic limb was performed to quantify the contribution of the extent of lower limb shortening and compensatory movements (such as hip elevation and circumduction) to toe clearance. The impact of each movement related to toe clearance was assessed by analyzing the change in the vertical direction. RESULTS: Using AFOs significantly increased toe clearance (p = 0.038). The quantified limb shortening and pelvic obliquity significantly differed between gaits performed with versus without AFOs. Among the movement indices related to toe clearance, limb shortening was increased by the use of AFOs (p < 0.0001), while hip elevation due to pelvic obliquity (representing compensatory strategies) was diminished by the use of AFOs (p = 0.003). The toe clearance strategy was not significantly affected by the stage of the hemiparetic condition (acute versus chronic) or the type of AFO (thermoplastic AFOs versus adjustable posterior strut AFOs). CONCLUSIONS: Simplified three-dimensional gait analysis was successfully used to quantify and visualize the impact of AFOs on the toe clearance strategy of hemiparetic patients. AFO use increased the extent of toe clearance and limb shortening during the swing phase, while reducing compensatory movements. This approach to visualization of the gait strategy possibly contributes to clinical decision-making in the real clinical settings. TRIAL REGISTRATION: UMIN000028946 . Registered 31 August 2017 (retrospectively registered). PMID- 29792213 TI - Rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in asymptomatic Chinese adult volunteers. AB - BACKGROUND: An increasing number of studies on spinal morphology in asymptomatic Asian and Western patients have been reported. Variation in spinal anatomy among patients is considered as the cause of wrong-level surgery in up to 40% of cases. The present study examined the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers. METHODS: From May 27, 2016, to November 11, 2017, a cohort of 325 asymptomatic Chinese adults meeting the study exclusion criteria was recruited. The radiographs were examined by a spine surgeon and a radiologist to assess the number of thoracic and lumbar vertebrae. RESULTS: In total, 293 volunteers were included in this study: 17 (5.8%) had 11 thoracic vertebrae, and 16 (5.5%) had 6 lumbar vertebrae. Among all volunteers, 12 (4.1%) had 7 cervical vertebrae (C), 11 thoracic vertebrae (T), and 5 lumbar vertebrae (L); 5 (1.7%) had 7C, 11T, and 6L; and 11 (3.8%) had 7C, 12T, and 6L. There was no difference between the findings of the spine surgeon and the radiologist. CONCLUSIONS: For the first time, this study describes the rate of presence of 11 thoracic vertebrae and 6 lumbar vertebrae in 293 asymptomatic Chinese adult volunteers. Variations in the number of thoracic and lumbar vertebrae tend to be ignored by spine surgeons. We encourage spinal surgeons and researchers to be aware of such variations when performing thoracic- and lumbar-level surgery and assessing spinal alignment and parameters. PMID- 29792214 TI - Association of serum bilirubin level with lung function decline: a Korean community-based cohort study. AB - BACKGROUND: Bilirubin has been reported to be associated with respiratory diseases due to its antioxidant action. We aimed to evaluate the relationship between serum bilirubin concentration and annual lung function decline in the Korean general population. METHODS: The study included 7986 subjects aged 40-69 years from the Ansung-Ansan cohort database I (2001-2002)-III (2005-2006). We analyzed the relationships between serum bilirubin level and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and mean forced expiratory flow between 25 and 75% of FVC (FEF25-75%) at baseline, as well as the annual average changes in these lung parameters. RESULTS: The FEV1, FVC, and FEF25-75% were significantly associated with serum bilirubin levels after adjustment for age, sex, body mass index (BMI), and smoking status (all P < 0.001). When stratified according to smoking status, these relationships were significant in never-smokers. Additionally, serum bilirubin level was negatively associated with the annual decline in FEV1 and FVC, and positively associated with the annual decline in FEV1/FVC after adjustment for age, sex, BMI, baseline lung function, and smoking status (all P < 0.001). CONCLUSIONS: We found significant associations of serum bilirubin levels with FEV1, FVC, and FEF25-75% in the general population, especially in never-smokers. Moreover, serum bilirubin levels were related with the annual decline in FEV1, FVC, and FEV1/FVC ratio. PMID- 29792212 TI - The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults. AB - BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (>=65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3-5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log10 RNA copies/MUl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. PMID- 29792215 TI - Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study. AB - BACKGROUND: Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. METHODS: One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. RESULTS: During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). CONCLUSIONS: In a real-world setting, LAACS in addition to elective open heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. TRIAL REGISTRATION: LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered. PMID- 29792218 TI - Sudden cardiac arrest under spinal anesthesia in a mission hospital: a case report and review of the literature. AB - BACKGROUND: Sudden cardiac arrest following spinal anesthesia is relatively uncommon and a matter of grave concern for any anesthesiologist as well as clinicians in general. There have been, however, several reports of such cases in the literature. Careful patient selection, appropriate dosing of the local anesthetic, volume loading, close monitoring, and prompt intervention at the first sign of cardiovascular instability should improve outcomes. The rarity of occurrence and clinical curiosity of this entity suggest reporting of this unusual and possibly avoidable clinical event. CASE PRESENTATION: We report the occurrence of unanticipated delayed cardiac arrest following spinal anesthesia in a 25-year-old Cameroonian man. Incidentally, the index patient was successfully resuscitated with timely and appropriate cardiopulmonary resuscitative measures. He went ahead to have emergency open appendectomy with good post-operative outcome and recovery. CONCLUSIONS: The management of such cardiac arrest under spinal anesthesia is very challenging in resource- limited settings such as ours. Anesthetists and clinicians need to be well informed of this grave complication. A good understanding of the physiologic changes caused by spinal anesthesia and its complications, adequate patient selection, respecting the contraindications of the procedure, adequate monitoring, and constant vigilance are of paramount importance to the eventual outcome. PMID- 29792217 TI - Hypoargininemia exacerbates airway hyperresponsiveness in a mouse model of asthma. AB - BACKGROUND: Asthma is a chronic respiratory condition, with airway hyperresponsiveness (AHR) and inflammation as hallmarks. The hypothesis that the substantially increased expression of arginase 1 in activated macrophages limits the availability of L-arginine for nitric oxide synthesis, and thus increases AHR in lungs of mice with experimentally induced allergic asthma was recently refuted by several studies. In the present study, we tested the hypothesis that, instead, a low circulating concentration of arginine aggravates AHR in the same murine asthma model. Female FVB F/A2 tg/tg transgenic mice, which overexpress rat arginase 1 in their enterocytes, exhibit a ~ 50% decrease of their plasma L arginine concentration. METHODS: Adult female F/A2 tg/tg mice and their wild-type littermates (F/A2 wt/wt ) were sensitized and challenged with ovalbumin (OVA/OVA). Lung function was assessed with the flexiVentTM system. Adaptive changes in the expression of arginine-metabolizing or -transporting enzymes, chemokines and cytokines, and lung histology were quantified with qPCR, ELISA, and immunohistochemistry, respectively. RESULTS: Reduction of circulating L arginine concentration significantly increased AHR in OVA/OVA-treated mice and, to a lesser extent, even in PBS/OVA-treated mice. The pulmonary inflammatory response in OVA/OVA-treated F/A2 tg/tg and F/A2 wt/wt mice was comparable. OVA/OVA-treated F/A2 tg/tg mice differed from similarly treated female mice, in which arginase 1 expression in lung macrophages was eliminated, by a complete absence of an adaptive increase in the expression of arginine-metabolizing or transporting enzymes. CONCLUSION: A reduction of the circulating L-arginine concentration rather than the macrophage-mediated increase of arginine catabolism worsens AHR. PMID- 29792216 TI - HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription. AB - BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. RESULTS: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation. Phosphorylation of Tat Ser-16 was reduced in cultured cells treated by a small molecule inhibitor of CDK2 and, to a lesser extent, an inhibitor of DNA-PK. Conditional knock-downs of CDK2 and PKR inhibited and induced one round HIV-1 replication respectively. HIV-1 proviral transcription was inhibited by Tat alanine mutants and partially restored by S16E mutation. Pseudotyped HIV-1 with Tat S16E mutation replicated well, and HIV-1 Tat S46E-poorly, but no live viruses were obtained with Tat S16A or Tat S46A mutations. TAR RNA binding was affected by Tat Ser-16 alanine mutation. Binding to cyclin T1 showed decreased binding of all Ser-16 and Ser-46 Tat mutants with S16D and Tat S46D mutationts showing the strongest effect. Molecular modelling and molecular dynamic analysis revealed significant structural changes in Tat/CDK9/cyclin T1 complex with phosphorylated Ser-16 residue, but not with phosphorylated Ser-46 residue. CONCLUSION: Phosphorylation of Tat Ser-16 induces HIV-1 transcription, facilitates binding to TAR RNA and rearranges CDK9/cyclin T1/Tat complex. Thus, phosphorylation of Tat Ser-16 regulates HIV-1 transcription and may serve as target for HIV-1 therapeutics. PMID- 29792219 TI - Effect of intensive glycaemic control on moderate hypoglycaemia and ICU length of stay in severe traumatic brain injury. PMID- 29792220 TI - Frailty measurement and its contribution to clinical care and health services: a commentary. AB - Frailty is associated with poorer quality of life and higher healthcare utilization and spending. Despite its importance, no clear consensus exists on the definition of frailty. The recent IJHPR article by Buch et al. significantly contributes to the advancement of Israel's understanding of frailty by estimating for the first time the prevalence of frailty in the country. This commentary discusses the context of past and current advancements in measuring frailty and discusses how frailty measurement can contribute to both clinical care and the organization of health services to care for frail older adults in Israel and other developed countries. PMID- 29792221 TI - Sex differences in cardiovascular epigenetics-a systematic review. AB - BACKGROUND: Differences in cardiovascular diseases are evident in men and women throughout life and are mainly attributed to the presence of sex hormones and chromosomes. Epigenetic mechanisms drive the regulation of the biological processes that may lead to CVD and are possibly influenced by sex. In order to gain an overview of the status quo on sex differences in cardiovascular epigenetics, we performed a systematic review. MATERIALS AND METHODS: A systematic search was performed on PubMed and Embase for studies mentioning cardiovascular disease, epigenetics, and anything related to sex differences. The search returned 3071 publications to be screened. Primary included publications focused on cardiovascular and epigenetics research. Subsequently, papers were assessed for including both sexes in their studies and checked for appropriate sex stratification of results. RESULTS: Two independent screeners identified 75 papers in the proper domains that had included both sexes. Only 17% (13 papers out of 75) of these publications stratified some of their data according to sex. All remaining papers focused on DNA methylation solely as an epigenetic mechanism. Of the excluded papers that included only one sex, 86% (24 out 28) studied males, while 14% (4 out of 28) studied females. CONCLUSION: Our overview indicates that the majority of studies into cardiovascular epigenetics do not show their data stratified by sex, despite the well-known sex differences in CVD. All included and sex-stratified papers focus on DNA methylation, indicating that a lot of ground is still to gain regarding other epigenetic mechanisms, like chromatin architecture, and histone modifications. More attention to sex in epigenetic studies is warranted as such integration will advance our understanding of cardiovascular disease mechanisms in men and women. PMID- 29792222 TI - Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013. AB - OBJECTIVE: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years). RESULTS: Gender-specific time trends in age adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74 years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity related factors. PMID- 29792223 TI - Culex flavivirus infection in a Culex pipiens mosquito colony and its effects on vector competence for Rift Valley fever phlebovirus. AB - BACKGROUND: Rift Valley fever is a mosquito-borne zoonotic disease that affects domestic ruminants and humans. Culex flavivirus is an insect-specific flavivirus that naturally exists in field mosquito populations. The influence of Culex flavivirus on Rift Valley fever phlebovirus (RVFV) vector competence of Culex pipiens has not been investigated. METHODS: Culex flavivirus infection in a Cx. pipiens colony was studied by Culex flavivirus oral feeding and intrathoracical inoculation. Similarly, vector competence of Cx. pipiens infected with Culex flavivirus was evaluated for RVFV. Infection, dissemination, transmission rates and transmission efficiency of Culex flavivirus-infected and non-infected Cx. pipiens artificially fed with RVFV infected blood were assessed. RESULTS: Culex flavivirus was able to infect Cx. pipiens after intrathoracically inoculation in Cx. pipiens mosquitos but not after Culex flavivirus oral feeding. Culex flavivirus did not affect RVFV infection, dissemination and transmission in Cx. pipiens mosquitoes. RVFV could be detected from saliva of both the Culex flavivirus-positive and negative Cx. pipiens females without significant differences. Moreover, RVFV did not interfere with the Culex flavivirus infection in Cx. pipiens mosquitoes. CONCLUSIONS: Culex flavivirus infected and non infected Cx. pipiens transmit RVFV. Culex flavivirus existing in field-collected Cx. pipiens populations does not affect their vector competence for RVFV. Culex flavivirus may not be an efficient tool for RVFV control in mosquitoes. PMID- 29792224 TI - Health technology assessment of public health interventions: an analysis of characteristics and comparison of methods-study protocol. AB - BACKGROUND: Conducting a health technology assessment (HTA) of public health interventions (PHIs) poses some challenges. PHIs are often complex interventions, which affect the number and degree of interactions of the aspects to be assessed. Randomized controlled trials on PHIs are rare as they are difficult to conduct because of ethical or feasibility issues. The aim of this study is to provide an overview of the methodological characteristics and to compare the applied assessment methods in HTAs on PHIs. METHODS: We will systematically search HTA agencies for HTAs on PHIs published between 2012 and 2016. We will identify the HTAs by screening the webpages of members of international HTA organizations. One reviewer will screen the list of HTAs on the webpages of members of international HTA organization, and a second review will double-check the excluded records. For this methodological review, we define a PHI as a population-based intervention on health promotion or for primary prevention of chronic or non-chronic diseases. Only full HTA reports will be included. At maximum, we will include a sample of 100 HTAs. In the case that we identify more than 100 relevant HTAs, we will perform a random selection. We will extract data on effectiveness, safety and economic as well as on social, cultural, ethical and legal aspects in a priori piloted standardized tables. We will not assess the risk of bias as we focus on exploring methodological features. Data extraction will be performed by one reviewer and verified by a second. We will synthesize data using tables and in a structured narrative way. DISCUSSION: Our analysis will provide a comprehensive and current overview of methods applied in HTAs on PHIs. We will discuss approaches that may be promising to overcome the challenges of evaluating PHIs. PMID- 29792225 TI - Correction to: Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. AB - Upon publication of the original article [1] it was highlighted by the authors that a transposition error affected Additional file 1, causing the misplacement of several columns and rendering the table difficult to read. This transposition does not influence any of the results nor analyses presented in the paper and has since been formally noted in this correction article; the corrected file is available here as an Additional File. The publisher apologizes for this error. PMID- 29792226 TI - Treatment of depression and/or anxiety - outcomes of a randomised controlled trial of the tree theme method(r) versus regular occupational therapy. AB - BACKGROUND: Depression and anxiety disorders are a major concern in western countries, and because these often have a negative affect on everyday life interventions based on activities in everyday life are needed. The Tree Theme Method(r) (TTM) is a client-centred occupational therapy intervention designed to increase the ability to cope with, and to enhance satisfaction with, everyday life, both at home and at work. The aim of this study was to compare the short term outcomes of the TTM intervention with regular occupational therapy treatment for people with depression and/or anxiety disorders. METHODS: This randomised controlled trial included patients from three counties in Sweden. Men and women with depression and/or anxiety disorders, ages 18 to 65, were randomised to either TTM or regular occupational therapy. Assessment data were collected at baseline and the follow-up directly after completing the intervention. Non parametric and parametric statistical methods were used. RESULTS: The questionnaires were answered by 118 patients at baseline and by 107 patients after completing the intervention. No significant differences in short term outcomes were found between the groups. Both groups showed positive significant outcomes regarding almost all aspects of activities in everyday life, psychological symptoms, and health-related and intervention-related aspects. CONCLUSIONS: Despite the lack of differences between the groups, the positive outcomes regarding activities in everyday life, psychological symptoms, and health-related aspects after completing the intervention indicates the need for further research on the long-term perspective of TTM compared to regular occupational therapy. TRIAL REGISTRATION: Clinical Trials.gov: NCT01980381 ; registered November 2013. PMID- 29792228 TI - Field evaluation of an immunochromatographic test for diagnosis of cystic and alveolar echinococcosis. AB - BACKGROUND: The larval stages of the tapeworms Echinocoocus granulosus and Echinococcus multilocularis are the causative agents of human cystic echinococcosis (CE) and human alveolar echinococcosis (AE), respectively. Both CE and AE are chronic diseases characterised by long asymptomatic periods of many years. However, early diagnosis of the disease is important if treatment and management of echinococcosis patients are to be successful. METHODS: A previously developed rapid diagnostic test (RDT) for the differential detection of CE and AE was evaluated under field conditions with finger prick blood samples taken from 1502 people living in the Ganzi Tibetan Autonomous Prefecture, China, a region with a high prevalence for both forms of human echinococcosis. The results were compared with simultaneously obtained abdominal ultrasonographic scans of the individuals. RESULTS: Using the ultrasonography as the gold standard, sensitivity and specificity, and the diagnostic accuracy of the RDT were determined to be greater than 94% for both CE and AE. For CE cases, high detection rates (95.6 98.8%) were found with patients having active cysts while lower detection rates (40.0-68.8%) were obtained with patients having transient or inactive cysts. In contrast, detection rates in AE patients were independent of the lesion type. The positive likelihood ratio of the RDT for CE and AE was greater than 20 and thus fairly high, indicating that a patient with a positive test result has a high probability of having echinococcosis. CONCLUSIONS: The results suggest that our previously developed RDT is suitable as a screening tool for the early detection of human echinococcosis in endemic areas. PMID- 29792229 TI - Characterization of MEDLE-1, a protein in early development of Cryptosporidium parvum. AB - BACKGROUND: Cryptosporidium spp. are important diarrhea-causing pathogens in humans and animals. Comparative genomic analysis indicated that Cryptosporidium specific MEDLE family proteins may contribute to host adaptation of Cryptosporidium spp., and a recent study of one member of this family, CpMEDLE-2 encoded by cgd5_4590, has provided evidence supporting this hypothesis. In this study, another member of the protein family, CpMEDLE-1 of Cryptosporidium parvum encoded by cgd5_4580, which is distinct from CpMEDLE-2 and has no signature motif MEDLE, was cloned, expressed and characterized to understand its function. METHODS: CpMEDLE-1 was expressed in Escherichia coli and polyclonal antibodies against the recombinant CpMEDLE-1 protein were prepared in rabbits. Quantitative PCR was used to analyze the expression profile of cgd5_4580 in C. parvum culture. Immunofluorescence staining was used to locate CpMEDLE-1 expression in life-cycle stages, and in vitro neutralization assay with antibodies was adopted to assess the role of the protein in C. parvum invasion. RESULTS: The results indicated that cgd5_4580 had a peak expression at 2 h of C. parvum culture. CpMEDLE-1 was located in the mid-anterior region of sporozoites, probably within the dense granules. The neutralization efficiency of anti-CpMEDLE-1 antibodies was approximately 40%. CONCLUSIONS: The differences in protein and gene expression profiles between CpMEDLE-1 and CpMEDLE-2 suggest that MEDLE proteins have different subcellular locations, are developmentally regulated, could be potentially involved in the transcriptional regulation of the expression of parasite or host proteins and may exert their functions in different stages of the invasion and development process. PMID- 29792227 TI - Integrated time course omics analysis distinguishes immediate therapeutic response from acquired resistance. AB - BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors. METHODS: To determine the dynamics of these molecular changes, we obtained high throughput omics data (RNA sequencing and DNA methylation) weekly during the development of cetuximab resistance in a head and neck cancer in vitro model. The CoGAPS unsupervised algorithm was used to determine the dynamics of the molecular changes associated with resistance during the time course of resistance development. RESULTS: CoGAPS was used to quantify the evolving transcriptional and epigenetic changes. Applying a PatternMarker statistic to the results from CoGAPS enabled novel heatmap-based visualization of the dynamics in these time course omics data. We demonstrate that transcriptional changes result from immediate therapeutic response or resistance, whereas epigenetic alterations only occur with resistance. Integrated analysis demonstrates delayed onset of changes in DNA methylation relative to transcription, suggesting that resistance is stabilized epigenetically. CONCLUSIONS: Genes with epigenetic alterations associated with resistance that have concordant expression changes are hypothesized to stabilize the resistant phenotype. These genes include FGFR1, which was associated with EGFR inhibitors resistance previously. Thus, integrated omics analysis distinguishes the timing of molecular drivers of resistance. This understanding of the time course progression of molecular changes in acquired resistance is important for the development of alternative treatment strategies that would introduce appropriate selection of new drugs to treat cancer before the resistant phenotype develops. PMID- 29792230 TI - Community health worker support to improve HIV treatment outcomes for older children and adolescents in Zimbabwe: a process evaluation of the ZENITH trial. AB - BACKGROUND: Community health worker (CHW)-delivered support visits to children living with HIV and their caregivers significantly reduced odds of virological failure among the children in the ZENITH trial conducted in Zimbabwe. We conducted a process evaluation to assess fidelity, acceptability, and feasibility of this intervention to identify lessons that could inform replication and scale up of this approach. METHODS: Field manuals kept by each CHW, records from monthly supervisory meetings, and participant data collected throughout the trial were used to assess the intervention's implementation. Data extracted from field manuals included visit type, content, and duration. Minutes from monthly supervisory meetings were used to capture CHW attendance. RESULTS: The trial enrolled 172 participants in the intervention arm of whom 5 subsequently refused all visits, 1 died before the intervention could be delivered, and 1 could not be located. Manuals for 8 participants were not returned, 3 were incorrectly entered, and 1 manual was lost. We had 154 manuals available for analysis. A total of 1553 visits were successfully conducted (median 11 per participant, range 1-20). Additionally, CHWs made 85 visits where they were unable to make contact with the family. Thirteen (8.4%) participants received 5 or fewer visits, 10 moved out of the study area, and 3 died. CHWs discussed disclosure with the child/family for over 89% of participants and assisted clients with developing and reviewing their personal treatment plan with over 85% of participants. Of the 20 CHWs (3 male, 17 female) selected to implement the intervention, 19 were retained at the end of the trial. CONCLUSIONS: The intervention was acceptable to participants with most receiving and accepting the required number of visits. Key strenghts were high staff retention and fidelity to the intervention. This community-based intervention was an acceptable and feasible approach to reduce virological failure among children living with HIV. TRIAL REGISTRATION: The ZENITH trial was registered on 25 October 2012 in the Pan African Clinical Trials Registry under the trial registration number PACTR201212000442288 . It can be found at http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR20121200 442288 . PMID- 29792231 TI - High burden of birthweight-lowering genetic variants in Africans and Asians. AB - BACKGROUND: Birthweight is an important predictor of infant morbidity and mortality, and is associated with cardiovascular diseases, obesity, and diabetes in childhood and adulthood. Birthweight and fetal growth show regional and population variations even under similar maternal conditions, and a large proportion of these differences are not explained by environmental factors. Whether and to what extent population genetic variations at key birthweight associated loci account for the residual birthweight disparities not explained by environmental determinants is unknown. We hypothesized that the cumulative burden of genetic variants with a birthweight-lowering effect (GRB) is different among ancestrally diverse populations. METHODS: Genotype data were extracted from phase 3 of the 1000 Genomes Project for 2504 participants from 26 global populations grouped into five super-populations. GRB was calculated in offspring as the weighted sum of the number of birthweight-lowering genetic variants of 59 autosomal single-nucleotide polymorphisms associated with birthweight, and comparisons were made between Europeans and non-Europeans. RESULTS: GRB was significantly higher in Africans (mean difference 3.15; 95% confidence interval 2.64, 3.66), admixed Americans (3.02; 2.34, 3.70), East Asians (2.85; 2.29, 3.41), and South Asians (1.07; 0.49, 1.65) compared to Europeans. Birthweight lowering genetic variants in Africans and East Asians were enriched for rare and frequency-fixed alleles (P < 0.001). African and Asian populations had the greatest deviation from the expectation of the common disease-common variant hyothesis. Compared to Europeans, the GRB of ancestral alleles was significantly higher and that of derived alleles was significantly lower in non-Europeans (P < 0.001). CONCLUSIONS: The burden of birthweight-lowering genetic variants is higher in Africans and East Asians. This finding is consistent with the high incidence of low birthweight in the two populations. The genetic variants we studied may not be causal and the extent to which they tag the causal variants in non-Europeans is unknown; however, our findings highlight that genetic variations contribute to population differences in birthweight. PMID- 29792234 TI - Long-term outcomes of acute treatment with cognitive therapy v. interpersonal psychotherapy for adult depression: follow-up of a randomized controlled trial. AB - BACKGROUND: Although equally efficacious in the acute phase, it is not known how cognitive therapy (CT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) compare in the long run. This study examined the long-term outcomes of CT v. IPT for MDD. METHODS: One hundred thirty-four adult (18-65) depressed outpatients who were treated with CT (n = 69) or IPT (n = 65) in a large open-label randomized controlled trial (parallel group design; computer generated block randomization) were monitored across a 17-month follow-up phase. Mixed regression was used to determine the course of self-reported depressive symptom severity (Beck Depression Inventory II; BDI-II) after treatment termination, and to test whether CT and IPT differed throughout the follow-up phase. Analyses were conducted for the total sample (n = 134) and for the subsample of treatment responders (n = 85). Furthermore, for treatment responders, rates of relapse and sustained response were examined for self reported (BDI-II) and clinician-rated (Longitudinal Interval Follow-up Evaluation; LIFE) depression using Cox regression. RESULTS: On average, the symptom reduction achieved during the 7-month treatment phase was maintained across follow-up (7-24 months) for CT and IPT, both in the total sample and in the responder sample. Two-thirds (67%) of the treatment responders did not relapse across the follow-up period on the BDI-II. Relapse rates assessed with the LIFE were somewhat lower. No differential effects between conditions were found. CONCLUSIONS: Patients who responded to IPT were no more likely to relapse following treatment termination than patients who responded to CT. Given that CT appears to have a prophylactic effect following successful treatment, our findings suggest that IPT might have a prophylactic effect as well. PMID- 29792232 TI - Effect of postoperative goal-directed therapy in cancer patients undergoing high risk surgery: a randomized clinical trial and meta-analysis. AB - BACKGROUND: Perioperative goal-directed hemodynamic therapy (GDHT) has been advocated in high-risk patients undergoing noncardiac surgery to reduce postoperative morbidity and mortality. We hypothesized that using cardiac index (CI)-guided GDHT in the postoperative period for patients undergoing high-risk surgery for cancer treatment would reduce 30-day mortality and postoperative complications. METHODS: A randomized, parallel-group, superiority trial was performed in a tertiary oncology hospital. All adult patients undergoing high risk cancer surgery who required intensive care unit admission were randomly allocated to a CI-guided GDHT group or to a usual care group. In the GDHT group, postoperative therapy aimed at CI >= 2.5 L/min/m2 using fluids, inotropes and red blood cells during the first 8 postoperative hours. The primary outcome was a composite endpoint of 30-day all-cause mortality and severe postoperative complications during the hospital stay. A meta-analysis was also conducted including all randomized trials of postoperative GDHT published from 1966 to May 2017. RESULTS: A total of 128 patients (64 in each group) were randomized. The primary outcome occurred in 34 patients of the GDHT group and in 28 patients of the usual care group (53.1% vs 43.8%, absolute difference 9.4 (95% CI, - 7.8 to 25.8); p = 0.3). During the 8-h intervention period more patients in the GDHT group received dobutamine when compared to the usual care group (55% vs 16%, p < 0.001). A meta-analysis of nine randomized trials showed no differences in postoperative mortality (risk ratio 0.85, 95% CI 0.59-1.23; p = 0.4; p for heterogeneity = 0.7; I2 = 0%) and in the overall complications rate (risk ratio 0.88, 95% CI 0.71-1.08; p = 0.2; p for heterogeneity = 0.07; I2 = 48%), but a reduced hospital length of stay in the GDHT group (mean difference (MD) - 1.6; 95% CI - 2.75 to - 0.46; p = 0.006; p for heterogeneity = 0.002; I2 = 74%). CONCLUSIONS: CI-guided hemodynamic therapy in the first 8 postoperative hours does not reduce 30-day mortality and severe complications during hospital stay when compared to usual care in cancer patients undergoing high-risk surgery. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT01946269 . Registered on 16 September 2013. PMID- 29792235 TI - The PERSONS score for symptoms assessment in simultaneous care setting: A pilot study. AB - One of the first steps to early integrate palliative care into oncology practice is a timely and efficient evaluation of symptoms (Bakitas et al., 2015; Davis et al., 2015; Temel et al., 2010). In a recent position paper, the Italian Association of Medical Oncology tells oncologists that they "must be able to prevent, recognize, measure, and treat all cancer-related symptoms" (Zagonel et al., 2017). Major international scientific societies such as the American Society of Clinical Oncology and the European Society of Medical Oncology have often defined the key role of symptoms evaluation and management to force the integration of palliative care into oncology (Davis et al., 2015; Ferrel et al., 2017). Nevertheless, a recent survey conducted by the Italian Association of Medical Oncology shows that only 20% of oncologists regularly uses valid tools to evaluate symptoms, 45% exclusively use them in the context of clinical trials, 30% use them only occasionally, and 5% never use them (Zagonel et al., 2016). PMID- 29792236 TI - Evaluation of Gamma Radiation-Induced Biochemical Changes in Skin for Dose Assesment: A Study on Small Experimental Animals. AB - OBJECTIVE: Researchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker. METHODS: Sprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx). RESULTS: Intra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value0.05). CONCLUSIONS: This study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2018;page 1 of 6). PMID- 29792233 TI - Antibiotic resistance and molecular characterization of diarrheagenic Escherichia coli and non-typhoidal Salmonella strains isolated from infections in Southwest China. AB - BACKGROUND: Bacterial diarrhea is one of the most common causes for medical consultations, mortality and morbidity in the world. Diarrheagenic Escherichia coli (DEC) and non-typhoidal Salmonella (NTS) are major intestinal pathogens in developing countries, and the indiscriminate use of antibiotics has greatly contributed to resistant strains. Hence, the aim of the present study is to identify the antimicrobial resistance patterns and the molecular characteristics of DEC and NTS in southwest, China. METHODS: 1121 diarrheal patients and 319 non diarrheal subjects across all age groups were recruited from four sentinel hospitals from June 2014 to July 2015 in Kunming City, Yunnan Province. Each stool specimen was collected to detect DEC and NTS with standard microbiological and molecular methods. Antimicrobial resistance testing was performed with the Kirby-Bauer disk diffusion method, and the standards for antimicrobial susceptibility testing complied with the Clinical and Laboratory Standards Institute (CLSI). Molecular characterization of strains was carried out using pulsed-field gel electrophoresis (PFGE). A structured questionnaire was used to record basic epidemiological data (e.g. sex, age, residence, season, etc.). Data were analyzed using Chi-square or Fisher's exact test. RESULTS: DEC was detected in 127 (11.33%) diarrhea cases and 9 (2.82%) non-diarrheal cases (chi2 = 20.69, P < 0.001, OR = 4.36, 95% CI: 2.19-8.65), and the prevalence of NTS isolated from diarrhea cases was higher than that of non-diarrheal cases across all age groups (n = 42, 3.75%, n = 1, 0.31%, chi2 = 10.10, P = 0.002, OR = 12.38, 95% CI: 1.70 90.29). The rates of resistance to ten antibiotics of DEC and NTS showed significant differences (chi 2 = 386.77, P < 0.001; chi2 = 191.16, P < 0.001). The rates of resistance to Amoxicillin and Clavulafiate (AMC), Cephalothin (CEP), Gentamicin (GEN) and Sulfamethoxazole-Trimethoprim (SXT) of DEC isolated from diarrhea cases were higher than those of NTS isolated from diarrhea patients (37.01% vs 14.29%, chi2 = 7.57, P = 0.006; 29.92% vs 11.90%, chi2 = 5.40, P = 0.02; 37.01% vs 11.90%, chi2 = 5.80, P = 0.016; 62.20% vs 26.19%, chi2 = 16.44, P < 0.001; respectively). Ciprofloxacin (CIP) was the most sensitive antibiotic for DEC and NTS strains isolated from diarrhea cases. Resistance rates of DEC isolates from cases and controls to more than three kinds antimicrobials (multidrug resistance, MDR) showed no significant differences (81.10% vs 88.89%, P = 0.33). Pulsotype patterns of DEC strains were highly diverse; however, the pulsotype pattern of NTS strains was closely related to the serotype. The pattern of S. enteritidis was highly similar, but the S. enterica Typhimurium strain was discrete. CONCLUSIONS: Antibiotic resistance of Enterobacteriaceae is of great concern. The societal effects of antibiotic use justify strict monitoring to combat increases in antimicrobial resistance. Molecular epidemiology and systematic epidemiological investigation can provide accurate evidence for tracking the infection source. PMID- 29792237 TI - According to mitochondrial DNA evidence, Parascaris equorum and Parascaris univalens may represent the same species. AB - Parascarosis is caused mainly by parasitic infections with Parascaris equorum and Parascaris univalens, the most common ascarid nematodes, in the small intestine of equines. Parascarosis often causes severe illness and even death in foals and yearlings. In this study, we obtained the complete sequence of the P. equorum mitochondrial (mt) genome and compared its organization and structure with that of P. equorum Japan isolate (nearly complete), and the complete mtDNA sequences of P. univalens Switzerland and USA isolates. The complete mtDNA genome of P. equorum China isolate is 13,899 base pairs (bp), making it the smallest of the four genomes. All four Parascaris mt genomes are circular, and all genes are transcribed in the same direction. The P. equorum mtDNA genome consists of 12 protein-coding genes, two ribosomal RNA genes, 22 transfer (t) RNA genes and one non-coding region, which is consistent with P. equorum Japan isolate and P. univalens Switzerland isolate but distinct from P. univalens USA isolate, which has 20 tRNA genes. Differences in nucleotide sequences of the four entire mt genomes range from 0.1-0.9%, and differences in total amino acid sequences of protein-coding genes are 0.2-2.1%. Phylogenetic analyses showed that the four Parascaris species clustered in a clade, indicating that P. equorum and P. univalens are very closely related. These mt genome datasets provide genetic evidence that P. equorum and P. univalens may represent the same species, which will be of use in further studies of the taxonomy, systematics and population genetics of ascarids and other nematodes. PMID- 29792239 TI - Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): Symptom profile and utility of individual items in the identification of delirium dependent on the level of sedation. AB - OBJECTIVE: The importance of the proper identification of delirium, with its high incidence and adversities in the intensive care setting, has been widely recognized. One common screening instrument is the Intensive Care Delirium Screening Checklist (ICDSC); however, the symptom profile and key features of delirium dependent on the level of sedation have not yet been evaluated. METHOD: In this prospective cohort study, the ICDSC was evaluated versus the Diagnostic and Statistical Manual, 4th edition, text revision, diagnosis of delirium set as standard with respect to the symptom profile, and correct identification of delirium. The aim of this study was to identify key features of delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale levels of sedation: drowsiness versus alert and calmness.ResultThe 88 delirious patients of 225 were older, had more severe disease, and prolonged hospitalization. Irrespective of the level of sedation, delirium was correctly classified by items related to inattention, disorientation, psychomotor alterations, inappropriate speech or mood, and symptom fluctuation. In the drowsy patients, inattention reached substantial sensitivity and specificity, whereas psychomotor alterations and sleep-wake cycle disturbances were sensitive lacked specificity. The positive prediction was substantial across items, whereas the negative prediction was only moderate. In the alert and calm patient, the sensitivities were substantial for psychomotor alterations, sleep-wake cycle disturbances, and symptom fluctuations; however, these fluctuations were not specific. The positive prediction was moderate and the negative prediction substantial. Between the nondelirious drowsy and alert, the symptom profile was similar; however, drowsiness was associated with alterations in consciousness.Significance of resultsIn the clinical routine, irrespective of the level of sedation, delirium was characterized by the ICDSC items for inattention, disorientation, psychomotor alterations, inappropriate speech or mood and symptom fluctuation. Further, drowsiness caused altered levels of consciousness. PMID- 29792238 TI - Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder. AB - BACKGROUND: While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication. METHODS: We acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.5; s.d. 18.4, 116 with ADHD). Using linear mixed model regression, we tested for associations between cognitive abilities (working memory, information processing, intelligence, and attention), symptoms and both cortical and subcortical volumes. RESULTS: Symptom severity was associated with spatial working memory (t = -3.77, p = 0.0002), processing speed (t = -2.95, p = 0.004) and a measure of impulsive responding (t = 2.19, p = 0.03); these associations did not vary with age (all p > 0.1). Neuroanatomic associations of cognition varied by task but centered on prefrontal, lateral parietal and temporal cortical regions, the thalamus and putamen. The neuroanatomic correlates of ADHD symptoms overlapped significantly with those of working memory (Dice's overlap coefficient: spatial, p = 0.003; verbal, p = 0.001) and information processing (p = 0.02). Psychostimulant medication history was associated with neither cognitive skills nor with a brain cognition relationships. CONCLUSIONS: Diagnostic differences in the cognitive profile of ADHD does not vary significantly with age; nor were cognitive differences associated with psychostimulant medication history. The neuroanatomic substrates of working memory and information overlapped with those for symptoms within these extended families, consistent with a pathophysiological role for these cognitive skills in familial ADHD. PMID- 29792240 TI - Posttraumatic Stress, Depression, and Coping Following the 2015 Nepal Earthquake: A Study on Adolescents. AB - OBJECTIVE: The study aimed to gather data on posttraumatic stress and depression in adolescents following the 2015 Nepal earthquake and explore the adolescents' coping strategies. METHODS: In a questionnaire-based, cross-sectional study about 1 year after the earthquake, adolescents in two districts with different degrees of impact were evaluated for disaster experience, coping strategies, and symptoms of posttraumatic stress and depression measured with the Child Posttraumatic Stress Scale and the Depression Self Rating Scale. RESULTS: In the studied sample (N=409), the estimated prevalence of posttraumatic stress disorder (PTSD) (43.3%) and depression (38.1%) was considerable. Prevalence of PTSD was significantly higher in the more affected area (49.0% v 37.9%); however, the prevalence figures were comparable in adolescents who reported a stress. The prevalence of depression was comparable. Female gender, joint family, financial problems, displacement, injury or being trapped in the earthquake, damage to livelihood, and fear of death were significantly associated with a probable PTSD diagnosis. Various coping strategies were used: talking to others, praying, helping others, hoping for the best, and some activities were common. Drug abuse was rare. Most of the coping strategies were comparable among the clinical groups. CONCLUSIONS: A considerable proportion of adolescents had posttraumatic stress and depression 1 year after the earthquake. There is a need for clinical interventions and follow-up studies regarding the outcome. Disaster Med Public Health Preparedness. 2018;page 1 of 7. PMID- 29792241 TI - Efficacy of digital CBT for insomnia to reduce depression across demographic groups: a randomized trial. AB - BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups. METHODS: Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects. RESULTS: The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants. CONCLUSIONS: Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population. PMID- 29792242 TI - Testing a stepped care model for binge-eating disorder: a two-step randomized controlled trial. AB - BACKGROUND: A stepped care approach involves patients first receiving low intensity treatment followed by higher intensity treatment. This two-step randomized controlled trial investigated the efficacy of a sequential stepped care approach for the psychological treatment of binge-eating disorder (BED). METHODS: In the first step, all participants with BED (n = 135) received unguided self-help (USH) based on a cognitive-behavioral therapy model. In the second step, participants who remained in the trial were randomized either to 16 weeks of group psychodynamic-interpersonal psychotherapy (GPIP) (n = 39) or to a no treatment control condition (n = 46). Outcomes were assessed for USH in step 1, and then for step 2 up to 6-months post-treatment using multilevel regression slope discontinuity models. RESULTS: In the first step, USH resulted in large and statistically significant reductions in the frequency of binge eating. Statistically significant moderate to large reductions in eating disorder cognitions were also noted. In the second step, there was no difference in change in frequency of binge eating between GPIP and the control condition. Compared with controls, GPIP resulted in significant and large improvement in attachment avoidance and interpersonal problems. CONCLUSIONS: The findings indicated that a second step of a stepped care approach did not significantly reduce binge-eating symptoms beyond the effects of USH alone. The study provided some evidence for the second step potentially to reduce factors known to maintain binge eating in the long run, such as attachment avoidance and interpersonal problems. PMID- 29792244 TI - Affective problems and decline in cognitive state in older adults: a systematic review and meta-analysis. AB - Evidence suggests that affective problems, such as depression and anxiety, increase risk for late-life dementia. However, the extent to which affective problems influence cognitive decline, even many years prior to clinical diagnosis of dementia, is not clear. The present study systematically reviews and synthesises the evidence for the association between affective problems and decline in cognitive state (i.e., decline in non-specific cognitive function) in older adults. An electronic search of PubMed, PsycInfo, Cochrane, and ScienceDirect was conducted to identify studies of the association between depression and anxiety separately and decline in cognitive state. Key inclusion criteria were prospective, longitudinal designs with a minimum follow-up period of 1 year. Data extraction and methodological quality assessment using the STROBE checklist were conducted independently by two raters. A total of 34 studies (n = 71 244) met eligibility criteria, with 32 studies measuring depression (n = 68 793), and five measuring anxiety (n = 4698). A multi-level meta-analysis revealed that depression assessed as a binary predictor (OR 1.36, 95% CI 1.05-1.76, p = 0.02) or a continuous predictor (B = -0.008, 95% CI -0.015 to -0.002, p = 0.012; OR 0.992, 95% CI 0.985-0.998) was significantly associated with decline in cognitive state. The number of anxiety studies was insufficient for meta analysis, and they are described in a narrative review. Results of the present study improve current understanding of the temporal nature of the association between affective problems and decline in cognitive state. They also suggest that cognitive function may need to be monitored closely in individuals with affective disorders, as these individuals may be at particular risk of greater cognitive decline. PMID- 29792245 TI - The over-35s: early intervention in psychosis services entering uncharted territory. AB - : Aims and methodFollowing the introduction of new standards for early intervention in psychosis (EIP) in England, EIP services are accepting referrals for people aged 35-65. The Cambridgeshire and Peterborough EIP service (CAMEO) aimed to explore the immediate implications for the service, especially with regards to referral numbers and sources. Data were collected from April 2016 to June 2017. RESULTS: Referrals for over-35s represented 25.7% of all new referrals. Fifty per cent of referrals for over-35s were accepted onto caseload (40.2% for under-35s). The over-35s were more likely to be referred from acute and secondary mental health services (P < 0.01) and had longer durations of untreated psychosis than the under-35s (P = 0.02).Clinical implicationsCAMEO has received a significantly higher number of referrals as a result of age inclusivity, with an increased proportion of patients suffering from severe, acute psychotic presentations and existing mental health difficulties. This has implications for service planning.Declaration of interestNone. PMID- 29792243 TI - Understanding the science of portion control and the art of downsizing. AB - Offering large portions of high-energy-dense (HED) foods increases overall intake in children and adults. This is known as the portion size effect (PSE). It is robust, reliable and enduring. Over time, the PSE may facilitate overeating and ultimately positive energy balance. Therefore, it is important to understand what drives the PSE and what might be done to counter the effects of an environment promoting large portions, especially in children. Explanations for the PSE are many and diverse, ranging from consumer error in estimating portion size to simple heuristics such as cleaning the plate or eating in accordance with consumption norms. However, individual characteristics and hedonic processes influence the PSE, suggesting a more complex explanation than error or heuristics. Here PSE studies are reviewed to identify interventions that can be used to downsize portions of HED foods, with a focus on children who are still learning about social norms for portion size. Although the scientific evidence for the PSE is robust, there is still a need for creative downsizing solutions to facilitate portion control as children and adolescents establish their eating habits. PMID- 29792246 TI - Servants of the dying: How The Death of Ivan Ilyich informs hospice care today. PMID- 29792247 TI - Spontaneous Version of Fetal Presentation in Twin Pregnancies During Third Trimester: Longitudinal Assessment. AB - Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28-31 weeks) and mid-third trimester (32-35 weeks). Fetal presentation was categorized as vertex or non vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this 'no change' group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable. PMID- 29792248 TI - Metataxonomic Analysis of Individuals at BMI Extremes and Monozygotic Twins Discordant for BMI. AB - OBJECTIVE: The human gut microbiota has been demonstrated to be associated with a number of host phenotypes, including obesity and a number of obesity-associated phenotypes. This study is aimed at further understanding and describing the relationship between the gut microbiota and obesity-associated measurements obtained from human participants. SUBJECTS/METHODS: Here, we utilize genetically informative study designs, including a four-corners design (extremes of genetic risk for BMI and of observed BMI; N = 50) and the BMI monozygotic (MZ) discordant twin pair design (N = 30), in order to help delineate the role of host genetics and the gut microbiota in the development of obesity. RESULTS: Our results highlight a negative association between BMI and alpha diversity of the gut microbiota. The low genetic risk/high BMI group of individuals had a lower gut microbiota alpha diversity when compared to the other three groups. Although the difference in alpha diversity between the lean and heavy groups of the BMI discordant MZ twin design did not achieve significance, this difference was observed to be in the expected direction, with the heavier participants having a lower average alpha diversity. We have also identified nine OTUs observed to be associated with either a leaner or heavier phenotype, with enrichment for OTUs classified to the Ruminococcaceae and Oxalobacteraceae taxonomic families. CONCLUSION: Our study presents evidence of a relationship between BMI and alpha diversity of the gut microbiota. In addition to these findings, a number of OTUs were found to be significantly associated with host BMI. These findings may highlight separate subtypes of obesity, one driven by genetic factors, the other more heavily influenced by environmental factors. PMID- 29792251 TI - Claiming and Naming Your Seat at the Multiauthorship Table. PMID- 29792252 TI - Resisting the Slow Undoing of Human Rights. PMID- 29792253 TI - Genocide Rape Trauma: A Conceptual Framework for Understanding the Psychological Suffering of Rwandan Survivors. AB - In 1994, the Rwandan genocide claimed the lives of approximately 1 million Tutsi and moderate Hutu citizens. Systematic rape was a strategic component of the Hutu extremist plan to eradicate the Tutsi minority population. This involved collective and repeated sexual assaults with brutal violence, public humiliation, and torture. This article maps the ongoing psychological impact on Rwandan genocide rape survivors and identifies implications for international nursing practice. The research formalizes their narratives, identifying a number of interconnected elements that combine to produce myriad forms of chronic psychological suffering in the Rwandan context. This work in turn reveals the specific needs of these survivors that may be addressed by nursing. It allows nurses, as experts in managing the human responses to health and illness, to develop a more complete understanding of psychological suffering as it pertains to vulnerable populations during and in the wake of extreme social conflict. This clarifies the roles of nurse educators, clinicians, and policy advocates as key agents in providing genocide rape survivors with the resources and expertise needed to effectively manage their ongoing trauma. PMID- 29792254 TI - Introduction of New Theory for Hand Hygiene Surveillance: Healthcare Environment Theory. AB - BACKGROUND AND PURPOSE: The purpose of this article is to introduce a theoretical foundation, the healthcare environment theory (HET), tested in a quantitative, cross-sectional, overt observational study measuring the association of demographic variables with consistent hand hygiene compliance of the ICU nurse. METHODS: Six environments found in a hospital ICU setting (family, church, work, administration, community, and culture) work bi-directionally to influence and be influenced by the nurse, simultaneously influencing each of the other environments in a multidirectional manner. The HET was used as the theoretical foundation for a study, which included a convenience sample of registered nurses (RNs) from five ICUs (64 participating RNs) in four hospitals in Texas who were observed for a total of 18 days (144 hours). The desired sample size of 613 hand hygiene opportunities for each ICU was obtained in 3 days of observation at 3 ICUs, 4 days in one ICU, and 5 days in one ICU. The six environments were used to support the results observed. RESULTS: Through the variables of age and having children, hand hygiene rates were influenced by the family environment. Community environment was associated with a change in hand hygiene behavior in hospital hand hygiene rates in regards to age of the nurse. Younger nurses had higher hand hygiene compliance rates than older nurses. IMPLICATIONS FOR PRACTICE: The different hospital environments surrounding the nurse can be used to explain hand hygiene compliance rates in association with demographic variables. PMID- 29792255 TI - Effectiveness of Adolescent Peer Education Programs on Reducing HIV/STI Risk: An Integrated Review. AB - There is empirical evidence suggesting that peer education is efficacious in changing adolescent sexual risk behaviors; however, it is unclear if there are similarities in outcomes across studies. Thus, the purpose of this review was to synthesize published research on peer-led HIV/STI intervention programs for adolescents in an effort to determine the efficacy of peer education on knowledge, attitudes, normative beliefs, and sexual behavior. Data collection included online searches of published research from Index Medicus (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Educational Resources Information Center (ERIC), Educational Index, and PsycINFO (including PsycARTICLES) from 2000 to 2016. Twenty-four quantitative and six qualitative studies were included in the review. There appears to be evidence of the effectiveness of adolescent peer-led HIV education programs on knowledge, attitudes, normative beliefs, and self-efficacy. However, the studies reviewed were equivocal on changes in sexual behavior. The findings of the qualitative/process studies demonstrated perceived program efficacy among staff and peer educators. Peer educators and students placed a high value on peer-led programs. Mediators and/or covariates such as culture, gender, sexual experience, and age may impact findings of adolescent peer intervention studies; therefore, these factors need to be considered when implementing and evaluating peer education programs. Peer education should also focus on variables that were gleaned from qualitative studies, such as the role of the community and altruistic roles. PMID- 29792256 TI - Uncaring Nurses: Mobilizing Power, Knowledge, Difference, and Resistance to Explain Workplace Violence in Academia. AB - BACKGROUND AND PURPOSE: Violence among nurses and in nursing academia is a significant issue, with attention increasingly focused on damage resulting from psychological violence, such as bullying, harassment, aggression, and incivility. Each workplace's interpretation of violence will impact individual behavior within the organization. Organizational and environmental factors can contribute to violent behaviors becoming normalized in the workplace. When violent behaviors go unconstrained, they become imbedded within the workplace culture. An increased understanding of workplace culture is required to address workplace violence. The purpose of this article is to demonstrate how the use of this theoretical framework can provide greater understanding of the role of workplace culture in sustaining violent behaviors in nursing academia. METHODS: The theoretical perspectives of Gail Mason on interpersonal violence and Michel Foucault on power were utilized to inform the research process and guide data analysis. RESULTS: The framework makes possible the exposure of a dominant discourse perpetuating violence in nursing academia. Power and violence were found to work together to shape knowledge and influence group norms and behaviors. IMPLICATIONS FOR PRACTICE: The framework is useful in providing greater understanding of how the concepts of power, knowledge, difference, and resistance support the enactment of workplace violence. Investigating the influence of these concepts in the development of accepted practices and discourses may allow greater insight into ways violence and power are used to negotiate and enforce organizational rules and norms. PMID- 29792257 TI - A Critique of the Shannon-Weaver Theory of Communication and Its Implications for Nursing. AB - With the Joint Commission's revelation that as much as 65%-70% of the time miscommunication has been discovered to be the root cause of many sentinel events, it may be time to examine a communication theory to support practice improvement efforts. Effective communication has been shown to decrease medical errors, improve patient satisfaction, and increase adherence to treatment plans leading to better health outcomes; yet very few studies have examined communication theories and their applicability to practice. This article will examine the Shannon-Weaver Communication Theory as one theory that may support future studies examining the teach-back communication method as a means to improving patient health literacy leading to improvements in clinical practice. PMID- 29792258 TI - Nurses' and Patients' Perceptions of the Quality of Psychiatric Nursing Care in Jordan. AB - BACKGROUND: The quality of care provided for patients in mental health-care facilities remains a challenge for health-care providers in general and for nurses in particular. Identifying the level of quality of care provided for patients in mental health-care facilities as perceived by nurses and patients may help health-care providers improve the quality of care and improve patients' outcomes. OBJECTIVES: The purpose of the study was to assess the perceptions of nurses and patients of the quality of nursing care, and explore the differences in their perceptions of quality of care in mental health-care facilities in Jordan. METHODS: A cross-sectional study was conducted using two convenience samples of 123 nurses and 150 patients. The nurses completed the Karen-personnel instrument, a self-administered questionnaire; One hundred and fifty patients from several mental health-care facilities in Jordan were interviewed using the Karen-patient instrument. The interviews were structured. RESULTS: Sixtyfour percent of nurses rated the quality of psychiatric nursing care as satisfactory, and 47.6% of patients perceived the quality of nursing care as satisfactory. Male nurses, who attended courses in mental health nursing, chose to work in a psychiatric unit, committed to work in the future in a psychiatric unit, and were providing indirect care have significantly higher perception of quality of psychiatric nursing care than their counterparts. Patients in military hospitals have significantly higher perception of quality of psychiatric nursing care than those in governmental ones (p < .05). IMPLICATIONS FOR PRACTICE: To improve the quality of care in psychiatric units, patients and nurses need to be educated about the quality indicators set by Joint Commission international standards related to mental health-care facilities. PMID- 29792259 TI - Going digital: a checklist in preparing for hospital-wide electronic medical record implementation and digital transformation. AB - Objective In an era of rapid digitisation of Australian hospitals, practical guidance is needed in how to successfully implement electronic medical records (EMRs) as both a technical innovation and a major transformative change in clinical care. The aim of the present study was to develop a checklist that clearly and comprehensively defines the steps that best prepare hospitals for EMR implementation and digital transformation.Methods The checklist was developed using a formal methodological framework comprised of: literature reviews of relevant issues; an interactive workshop involving a multidisciplinary group of digital leads from Queensland hospitals; a draft document based on literature and workshop proceedings; and a review and feedback from senior clinical leads.Results The final checklist comprised 19 questions, 13 related to EMR implementation and six to digital transformation. Questions related to the former included organisational considerations (leadership, governance, change leaders, implementation plan), technical considerations (vendor choice, information technology and project management teams, system and hardware alignment with clinician workflows, interoperability with legacy systems) and training (user training, post-go-live contingency plans, roll-out sequence, staff support at point of care). Questions related to digital transformation included cultural considerations (clinically focused vision statement and communication strategy, readiness for change surveys), management of digital disruption syndromes and plans for further improvement in patient care (post-go-live optimisation of digital system, quality and benefit evaluation, ongoing digital innovation).Conclusion This evidence-based, field-tested checklist provides guidance to hospitals planning EMR implementation and separates readiness for EMR from readiness for digital transformation.What is known about the topic? Many hospitals throughout Australia have implemented, or are planning to implement, hospital wide electronic medical records (EMRs) with varying degrees of functionality. Few hospitals have implemented a complete end-to-end digital system with the ability to bring about major transformation in clinical care. Although the many challenges in implementing EMRs have been well documented, they have not been incorporated into an evidence-based, field-tested checklist that can practically assist hospitals in preparing for EMR implementation as both a technical innovation and a vehicle for major digital transformation of care.What does this paper add? This paper outlines a 19-question checklist that was developed using a formal methodological framework comprising literature review of relevant issues, proceedings from an interactive workshop involving a multidisciplinary group of digital leads from hospitals throughout Queensland, including three hospitals undertaking EMR implementation and one hospital with complete end-to-end EMR, and review of a draft checklist by senior clinical leads within a statewide digital healthcare improvement network. The checklist distinguishes between issues pertaining to EMR as a technical innovation and EMR as a vehicle for digital transformation of patient care.What are the implications for practitioners? Successful implementation of a hospital-wide EMR requires senior managers, clinical leads, information technology teams and project management teams to fully address key operational and strategic issues. Using an issues checklist may help prevent any one issue being inadvertently overlooked or underemphasised in the planning and implementation stages, and ensure the EMR is fully adopted and optimally used by clinician users in an ongoing digital transformation of care. PMID- 29792260 TI - Widening participation of Maori and Pasifika students in health careers: evaluation of two health science academies. AB - Objective The aim of the present study was to evaluate the short-term outcomes of two health science academies established by a district health board in South Auckland, New Zealand, to create a health workforce pipeline for local Maori and Pasifika students.Methods A mixed-methods approach was used, involving background discussions with key informants to generate an initial logic model of how the academies work, followed by secondary analysis of students' records relating to retention and academic achievement, a survey of senior academy students' interest in particular health careers and face-to-face interviews and focus groups with students, families and teachers.Results Academy students are collectively achieving better academic results than their contemporaries, although selection decisions are likely to contribute to these results. Academies are retaining students, with over 70% of students transitioning from Year 11 to Years 12 and 13. Senior students are expressing long-term ambitions to work in the health sector.Conclusions Health science academies show promise as an innovative approach to supporting Maori and Pasifika students prepare for a career in the health professions. Evaluating the long-term outcomes of the academies is required to determine their contribution to addressing inequities in the local health workforce.What is known about the topic? Despite progress in health workforce participation for underrepresented indigenous and ethnic minority groups in New Zealand, significant disparities persist. Within this context, a workforce development pipeline that targets preparation of secondary school students is recommended to address identified barriers in the pursuit of health careers.What does this paper add? We provide an evaluation of an innovative district health board initiative supporting high school students that is designed to ensure their future workforce is responsive to the needs of the local community.What are the implications for practitioners? The findings have implications for decision makers in health workforce planning regarding the benefits of investing at an early stage of the workforce development pipeline in order to build an equitable and diverse health professions workforce. PMID- 29792263 TI - An update on the use of immunohistochemistry and molecular pathology in the diagnosis of pre-invasive and malignant lesions in gynecological oncology. AB - OBJECTIVE: One of the most common challenges in everyday clinical practice of gynecological oncology is to identify the type and the primary origin of a tumor. This is a crucial step in the management, treatment, prognosis, and survival of patients suffering from a gynecological malignancy. Immunohistochemistry has been widely adopted over the last three decades in pathology laboratories all over the world. Recent advances in our understanding of the differentiation of gynecological tumors based on immunohistochemical expression have resulted in use of immunohistochemistry as a major diagnostic tool in gynecology, for precise tumor classification. More recently, advances in molecular pathology, have taken this disease sub-classification further resulting in more effective personalised treatment regimens. The aim of this review is to provide clinicians with up to date information on the various immunohistochemical and molecular tests used in the diagnosis of gynecological malignancies of the female genital tract and an understanding of how to interpret them. METHODS: We performed a review of the current literature including review articles, original research articles, and guidelines on various immunohistochemical markers and molecular techniques which are used for the differential diagnosis of gynecologic malignancies. CONCLUSIONS: Immunohistochemistry is useful as an objective means for improved diagnostic reproducibility, accuracy, and precise classification in cases where the diagnosis with histochemical stains is inconclusive, providing a more reliable estimate of clinical outcomes. The diagnosis, in some cases, can be further refined by the use of molecular techniques leading to personalised medical treatments. PMID- 29792264 TI - Paradoxical brain embolism shadowing massive pulmonary embolism. AB - Patent foramen ovale is frequently observed in the general population. In case of massive pulmonary embolism, the sudden increase in the right heart cavity's pressure may cause a right-to-left shunting across this foramen, which could be associated with conflicting outcomes. Herein, we report a case of reversible cardiac arrest preceded by seizures, and followed by hemodynamic stability without any vasopressor. A brain CT-scan showed a limited ischemic stroke. Initial echocardiographic assessment revealed an acute cor pulmonale and a right to-left intracardiac shunt across a large patent foramen ovale, suggesting the diagnosis of massive pulmonary embolism that was lately confirmed by a multidetector CT-angiography. Anticoagulation therapy was rapidly complicated by a hemorrhagic transformation of the ischemic stroke leading to a fatal outcome. This case illustrates the double-edged circulatory effect of shunting across a patent foramen ovale in case of massive pulmonary embolism: it may have limited circulatory failure but caused in the meanwhile a fatal paradoxical brain embolism. PMID- 29792262 TI - Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors. AB - Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the "pure" effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance. PMID- 29792261 TI - Structure-based analysis of CysZ-mediated cellular uptake of sulfate. AB - Sulfur, most abundantly found in the environment as sulfate (SO42-), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. However, current understanding of the cellular delivery of SO42- at the molecular level is limited. CysZ has been described as a SO42- permease, but its sequence family is without known structural precedent. Based on crystallographic structure information, SO42- binding and flux experiments, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ structures from three different bacterial species display a hitherto unknown fold and have subunits organized with inverted transmembrane topology. CysZ from Pseudomonas denitrificans assembles as a trimer of antiparallel dimers and the CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues. PMID- 29792266 TI - Gone but not forgotten: resolution of childhood kidney disease and the risk of end-stage kidney disease in adults. PMID- 29792267 TI - Isotonic fluids for volume resuscitation: is it really 6 liters of one, half a dozen of another? PMID- 29792268 TI - Toward individual glomerular phenotyping: advent of precision medicine in kidney biopsies. AB - The road to precision medicine for nephrology is approaching quickly. In the present volume, the glomerular proteome has now been characterized at a single glomerulus level in mouse and human kidneys. Using the Single-Pot Solid-Phase enhanced Sample Preparation (SP3) approach the authors demonstrated that LAMP1 is a key lysosomal protein that is increased in glomerular diseases and may play a pathogenic role. PMID- 29792269 TI - PCSK9 inhibition: ready for prime time in CKD? AB - Lowering LDL cholesterol reduces the risk of atherosclerotic vascular disease in a wide range of patients with chronic kidney disease, with no evidence of a threshold below which further reductions no longer reduce risk. Statins safely lower LDL cholesterol, but novel inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9) provide additional reductions which may reduce atherosclerotic vascular disease yet further in this high risk population. PMID- 29792270 TI - "Biomarking" the transition from genetic risk to kidney disease. AB - Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these findings should translate into improved longitudinal risk assessment for this high-risk population and might also provide additional insights regarding sites and mechanisms of APOL1 nephropathy. PMID- 29792271 TI - DNA methylation yields epigenetic clues into the diabetic nephropathy of Pima Indians. AB - Environmental factors drive epigenetic programming. DNA methylation is the best studied modification transmitting epigenetic information. A study by Qiu et al. examined potential epigenetic roots for the decline of renal function in Pima Indians. A genomewide survey of blood leukocytes uncovered differentially methylated DNA sites in regulatory regions of genes associated with chronic kidney disease. This longitudinal study provides the first clues on epigenetic links between environmental factors and a high prevalence of diabetic kidney disease in Pima Indians. PMID- 29792272 TI - Facing cinacalcet-induced hypocalcemia: sit back and relax? AB - A post hoc analysis of data from the EVOLVE study demonstrates that cinacalcet induced hypocalcemia is common, mostly asymptomatic, and resolves spontaneously. These findings are reassuring and may warrant therapeutic inertia. However, previous studies in parathyroidectomized patients suggest that calcium repletion may be beneficial and safe from bone and cardiovascular perspectives, respectively, and as such call into question the appropriateness of a "sit back and relax" attitude toward cinacalcet-induced hypocalcemia. PMID- 29792273 TI - Heterogeneity of renal cortical oxygenation: seeing is believing. AB - The limited spatial and temporal resolution of available methods for quantifying renal tissue oxygen tension is a major impediment to identification of the roles of renal hypoxia in kidney diseases. Intravital phosphorescence lifetime imaging microscopy allows cellular oxygen tension in the renal cortex of live animals to be resolved to the level of individual tubular cross-sections. This paves the way for future investigations of the spatial relationships between cellular hypoxia and pathophysiological events in kidney disease. PMID- 29792274 TI - Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy. AB - Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients. Heparinized blood from 200 individuals including healthy controls, dialysis patients with end stage renal disease and patients 1, 5, 10, 15, 20 years after kidney transplantation were analyzed. Differentiation and maturation of nTregs were studied by flow cytometry in order to compare dialysis patients and kidney transplanted patients under maintenance immunosuppression to healthy controls. CD127 expressing CD4+CD25highFoxP3+ nTregs were detectable at increased frequencies in dialysis patients with no negative impact on the nTreg end product quality and therapeutic usefulness of the ex vivo expanded nTregs. Further, despite that immunosuppression mildly altered nTreg maturation, neither dialysis nor pharmacological immunosuppression or previous acute rejection episodes impeded nTreg survival in vivo. Accordingly, the generation of autologous, highly pure nTreg products is feasible and qualifies patients awaiting or having received allogenic kidney transplantation for adoptive nTreg therapy. Thus, our novel treatment approach may enable us to reduce the incidence of organ rejection and reduce the need of long-term immunosuppression. PMID- 29792275 TI - Collagen type III glomerulopathy. PMID- 29792276 TI - Late renal revascularization and salvage due to unexpected collaterals. PMID- 29792277 TI - The Case | A 69-year-old man with bladder carcinoma and renal lesions. PMID- 29792278 TI - A novel endoscopic grading system for prediction of disease-related outcomes in patients with diverticulosis. AB - BACKGROUND: We describe a simple endoscopic grading system of diverticular disease for the assessment of disease severity and prediction of outcomes. METHODS: A retrospective analysis of prospectively maintained colonoscopy database was conducted. A single endoscopist prospectively graded disease severity according to the number and size of diverticula, the degree of muscular hypertrophy and rigidity of the sigmoid colon. RESULTS: 762 patients were included in the analysis. Mean patient age was 70 years (range 37-97). Endoscopic severity of diverticulosis was predictive of the need for surgery, with 2% in the mild-moderate, 12% in the severe and 33% in the acute group (p < 0001). Time to surgery showed correlation to severity grade, with mean periods of 107.5 months in the moderate group vs. 3 and 2.5 months in the severe and acute group (p < 0001). The mean follow up was 11 years. CONCLUSION: Surgeons should consider using endoscopic grading as an adjunct to clinical management decisions. PMID- 29792279 TI - Can intraoperative measurement of bone quality help in decision making for cementless unicompartmental knee arthroplasty? AB - BACKGROUND: In uncemented total hip arthroplasty (THA), low bone mineral density (BMD) is associated with aseptic loosening. BMD is usually assessed via dual energy X-ray absorptiometry (DXA) or quantitative computed tomography, which takes time and exposes patients to radiation. Due to its low risk profile, intraoperative measurement of the trabecular stability might be a useful alternative to DXA. METHODS: In 24 human femora, BMD was analysed using DXA at the femoral necks and the knees. Performing the standard Oxford Unicompartmental Knee Arthroplasty (OUKA) implantation procedure, a wingblade (DensiProbe) coupled to a torque probe was used to evaluate the trabecular peak torque. The standard procedure was modified: before the completion of the central peg drill hole, the DensiProbe was inserted into the pre-drilled hole and then turned until a loss of resistance was achieved. The obtained data was then correlated with BMD at the femoral neck as well as the knee. RESULTS: In all tested regions, a higher peak torque was observed in correlation with a higher BMD. CONCLUSIONS: As demonstrated, the DensiProbe can be a helpful tool to assess the bone quality intraoperatively in OUKA. It can be a valuable decision guidance when faced with choosing between a cemented and a cementless implant. Due to the fact that the central peg hole of the OUKA can be used for the procedure, no additional risk for the patient exists, while the additional work for the surgeon is minimal. PMID- 29792280 TI - Resource utilization and indications for helicopter transport of head-injured children. AB - INTRODUCTION: Helicopter emergency medical services (HEMS) have provided benefit for severely injured patients. However, HEMS are likely overused for the transportation of both adult and pediatric trauma patients. In this study, we aim to evaluate the degree of overuse of helicopter as a mode of transport for head injured children. In addition, we propose criteria that can be used to determine if a particular patient is suitable for air versus ground transport. MATERIALS AND METHODS: We identified patients who were transported to our facility for head injuries. We included only those patients who were transported from another facility and who were seen by the neurosurgical service. We recorded a number of data points including age, gender, race, Glasgow Coma Score (GCS), and intubation status. We also collected data on a number of imaging findings such as mass effect, edema, intracranial hemorrhage, and skull fractures. Patients undergoing emergent nonneurosurgical intervention were excluded. RESULTS: Of the 373 patients meeting inclusion criteria, 116 (31.1%) underwent a neurosurgical procedure or died and were deemed appropriate for helicopter transport. The remaining 68.9% of patients survived their injuries without neurosurgical intervention and were deemed nonappropriate for helicopter transport. Multivariable logistic regression identified GCS 3-8 and/or presence of mass effect, edema, epidural hematoma (EDH), and open-depressed skull fracture as appropriate indications for helicopter transport. CONCLUSIONS: The majority of patients transported to our facility by helicopter survived their head injury without need for neurosurgical intervention. Only those patients meeting clinical (GCS 3-8) or radiographic (mass effect, edema, EDH, open-depressed skull fracture) criteria should be transported by air. LEVEL OF EVIDENCE: Level III (Diagnostic Study). PMID- 29792282 TI - Reply to letter to the editor. PMID- 29792283 TI - Repurposing available drugs for neurodevelopmental disorders: The fragile X experience. AB - Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms has guided the choice of drugs for clinical trials, and several notable successes in fragile X clinical trials have led to common use of drugs such as minocycline in routine medical practice. Newer technologies like Disease-Gene Expression Matching (DGEM) may allow for more rapid identification of promising repurposing candidates. A DGEM study predicted that sulindac could be therapeutic for fragile X, and subsequent preclinical validation studies have shown promising results. The use of combinations of available drugs and nutraceuticals has the potential to greatly expand the options for repurposing, and may even be a viable business strategy. PMID- 29792281 TI - The impact of body weight on stapled anastomosis in pediatric patients. AB - PURPOSE: The purpose of this study is to clarify the impact of body weight on outcomes of stapled anastomosis in pediatric patients. METHODS: A total of 253 pediatric patients who underwent intestinal anastomosis were classified according to body weight (<3.5 kg: light group, >=3.5 kg: heavy group), and clinical outcomes of stapled and hand-sewn anastomoses were compared. RESULTS: The light and heavy groups included 77 (stapled: n = 13, hand-sewn: n = 64) and 176 (stapled: n = 58, hand-sewn: n = 118) patients, respectively. In both groups, stapled anastomosis was associated with reduced time to initial oral feeding (light group: 4 vs. 7 days, p = 0.006; heavy group: 3 vs. 5 days, p < 0.001) and full feeding (light group: 12 vs. 16 days, p = 0.026; heavy group: 7 vs. 9 days, p = 0.001), whereas its complication rate was not significantly different from that of hand-sewn anastomosis (light group: 30.8 vs. 12.5%, p = 0.112; heavy group: 3.4 vs. 2.5%, p = 0.665). In patients who underwent stapled anastomosis, the complication rate was significantly higher in the light group (30.8 vs. 3.4%, p = 0.009), with two cases of volvulus related to anastomotic dilatation. CONCLUSIONS: Stapled anastomosis is an effective procedure facilitating prompt oral feeding. However, the risk of complications, including volvulus related to anastomotic dilatation, should be considered among patients weighing <3.5 kg. LEVEL OF EVIDENCE: III. PMID- 29792284 TI - Influence of large hiatus hernia on cardiac volumes. A prospective observational cohort study by cardiovascular magnetic resonance. AB - BACKGROUND: Large hiatus hernia (LHH) is often associated with post-prandial dyspnea, palpitations or chest discomfort, but its effect on cardiac volumes and performance is still debated. METHODS AND RESULTS: Before and 3-months after laparoscopic repair, 35 patients underwent cardiovascular magnetic resonance (CMR) in the fasting state and after a standardized meal. Preoperatively, LHH size increased significantly after meal (p < 0.010). Compared to the fasting state, a systematic trend of volume reduction of the cardiac chambers was observed. In addition, both the left ventricle stroke volume (p = 0.012) and the ejection fraction (p = 0.010) were significantly reduced. At 3-months after surgery there was a statistically significant increase in left atrial volume (p = 0.029), overall left ventricle volume (p < 0.05) and right ventricle end-systolic volume (p = 0.046). Both FEV1 (Forced expiratory volume) (p = 0.02) and FVC (Forced Vital Capacity) (p = 0.01) values significantly improved after surgery. Cardiorespiratory symptoms significantly improved compared to pre-operative values (p < 0.01). CONCLUSIONS: The global heart function was significantly impaired by a standardized meal in the presence of a LHH. Restoration of the cardiac physiological status and improvement of clinical symptoms were noted after surgery. A multidisciplinary evaluation and CMR with a challenge meal may be added to routine pre-operative testing to select symptomatic patients for surgical hernia repair. PMID- 29792285 TI - Associations between trunk postural control in walking and unstable sitting at various levels of task demand. AB - Trunk postural control (TPC) has been investigated in several populations and tasks. Previous work observed targeted training of TPC via isolated trunk control tasks may improve performance in other activities (e.g., walking). However, the nature of this relationship remains unknown. We therefore investigated the relationship between TPC, at both the global (i.e., response to finite perturbations) and local (i.e., resistance to continuous perturbations) levels, during walking and unstable sitting, both at varying levels of task demand. Thirteen individuals (11 Male, 2 Female) with no recent history (past 12 months) of illness, injury, or musculoskeletal disorders walked on a dual-belt treadmill at four speeds (-20%, -10%, +10%, and + 20% of self-selected walking speed) and completed an unstable sitting task at four levels of chair instability (100, 75, 60, and 45% of an individual's "neutral" stability as defined by the gravitational gradient). Three-dimensional trunk and pelvic kinematics were collected. Tri-planar Lyapunov exponents and sample entropy characterized local TPC. Global TPC was characterized by ranges of motion and, for seated trials, metrics derived from center-of-pressure time series (i.e., path length, 95% confidence ellipse area, mean velocity, and RMS position). No strong or significant correlations (-0.057 < rho < 0.206) were observed between local TPC during walking and unstable sitting tasks. However, global TPC declined in both walking and unstable sitting as task demand increased, with a moderate inter-task relationship (0.336 < rho < 0.544). While the mechanisms regulating local TPC are inherently different, global TPC may be similarly regulated across both tasks, supporting future translation of improvements in TPC between tasks. PMID- 29792286 TI - [Prevalence of hydroxychloroquine-induced side-effects in dermatology patients: A retrospective survey of 102 patients]. AB - AIM: Our aim was to assess the prevalence of adverse effects (AEs) pertaining to the use and withdrawal of hydroxychloroquine (HCQ) in dermatological outpatients. PATIENTS AND METHODS: We conducted a retrospective study between January 2013 and June 2014 that included consecutive patients currently or previously receiving HCQ seen in our department. AEs were collated using a standardized questionnaire and validated by clinical and laboratory examination. Drug causality was evaluated using the updated French drug reaction causality assessment method. The main evaluation criterion was the prevalence of AEs in which HCQ had an intrinsic imputability score of I>2. RESULTS: We included 102 patients (93 of whom were women, with a median age of 44.5; range: 22-90years). HCQ was given for cutaneous lupus in most cases (n=70). At least one AE was reported for 55 patients. Among the 91 reported AEs, 59 (65%) had an HCQ intrinsic imputability score I>2. AEs were responsible for permanent HCQ discontinuation in 19 cases. Of these, 8 were unrelated to HCQ based on imputability score. The most common AEs associated with HCQ were gastrointestinal and cutaneous signs. Of the 8 patients diagnosed with retinopathy, only 3 were confirmed after reevaluation. CONCLUSION: AEs associated with HCQ were reported for over 50% of patients and were responsible for permanent HCQ discontinuation in one-third of cases. A more in-depth evaluation of imputability seems necessary, particularly regarding ophthalmological symptoms, since in two thirds of cases the reasons for discontinuation were not related to HCQ. PMID- 29792287 TI - Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. People with IPF have increased concentrations of autotaxin in lung tissue and lysophosphatidic acid (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is a novel, potent, selective autotaxin inhibitor with good oral exposure. We explored the effects of GLPG1690 in patients with IPF. METHODS: This was a randomised, double-blind, placebo-controlled phase 2a study done in 17 centres in Italy, Ukraine and the UK. Eligible patients were aged 40 years or older, non-smokers, not taking pirfenidone or nintedanib, and had a centrally confirmed diagnosis of IPF. We used a computer-generated randomisation schedule to assign patients 1:3 to receive placebo or 600 mg oral GLPG1690 once daily for 12 weeks. The primary outcomes were safety (adverse events), tolerability, pharmacokinetics, and pharmacodynamics. Spirometry was assessed as a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02738801. FINDINGS: Between March 24, 2016, and May 2, 2017, 72 patients were screened., of whom 49 were ineligible and 23 were enrolled in eight centres (six in Ukraine and two in the UK). Six patients were assigned to receive placebo and 17 to receive GLPG1690. 20 patients completed the study after one in each group discontinued because of adverse events and one in the GLPG1690 group withdrew consent. Four (67%) patients in the placebo group and 11 (65%) in the GLPG1690 group had treatment-emergent adverse events, most of which were mild to moderate. The most frequent events in the GLPG1690 group were infections and infestations (ten events) and respiratory, thoracic, and mediastinal disorders (eight events) with no apparent differences from the placebo group. Two (12%) patients in the GLPG1690 group had events that were judged to be related to treatment. Serious adverse events were seen in two patients in the placebo group (one had a urinary tract infection, acute kidney injury, and lower respiratory tract infection and the other had atrioventricular block, second degree) and one in the GLPG1690 group (cholangiocarcinoma that resulted in discontinuation of treatment). No patients died. The pharmacokinetic and pharmacodynamic profiles of GLPG1690 were similar to those previously shown in healthy controls. LPA C18:2 concentrations in plasma were consistently decreased. Mean change from baseline in forced vital capacity at week 12 was 25 mL (95% CI -75 to 124) for GLPG1690 and -70 mL (-208 to 68 mL) for placebo. INTERPRETATION: Our findings support further development of GLPG1690 as a novel treatment for IPF. FUNDING: Galapagos. PMID- 29792288 TI - Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. AB - BACKGROUND: Tralokinumab is an anti-interleukin-13 human monoclonal antibody developed for the treatment of severe, uncontrolled asthma. These clinical trials aimed to assess the efficacy and safety of tralokinumab in this population. METHODS: STRATOS 1 and STRATOS 2 were randomised, double-blind, parallel-group, placebo-controlled, phase 3 clinical trials that enrolled participants aged 12-75 years with severe asthma that was inadequately controlled despite use of inhaled corticosteroids (>=500 MUg per day fluticasone or equivalent) and a long-acting beta2 agonist (but not oral corticosteroids). STRATOS 1 was done at 246 sites in 14 countries, and STRATOS 2 was done at 242 sites in 13 countries. In STRATOS 1, participants were randomly assigned (2:1) to receive tralokinumab 300 mg or matching placebo subcutaneously every 2 weeks or every 4 weeks for 52 weeks. In STRATOS 2, participants were randomly assigned (1:1) to receive tralokinumab 300 mg or matching placebo subcutaneously every 2 weeks for 52 weeks. STRATOS 1 attempted to identify a biomarker-positive population with enhanced tralokinumab benefit, which was then tested in STRATOS 2. The primary endpoint was the annualised asthma exacerbation rate (AAER) reduction at week 52 in the all-comers population for STRATOS 1 and in the biomarker-positive population for STRATOS 2. All efficacy analyses for both trials were done on the full analysis set by an intention-to-treat approach. The safety analysis set comprised any participant who received the investigational drug and was categorised by treatment received. These trials are registered with ClinicalTrials.gov, numbers NCT02161757 (STRATOS 1) and NCT02194699 (STRATOS 2), and with the EU Clinical Trials Register, EudraCT 2013-005614-35 (STRATOS 1) and EudraCT 2013-005615-27 (STRATOS 2). FINDINGS: STRATOS 1 was done between June 13, 2014, and Feb 28, 2017. 1207 participants were randomly assigned and 1202 treated as follows: tralokinumab every 2 weeks (n=398), tralokinumab every 4 weeks (n=404), or placebo (n=400). STRATOS 2 was done between Oct 30, 2014, and Sept 21, 2017. 856 participants were randomly assigned and 849 treated as follows: tralokinumab every 2 weeks (n=427) and placebo every 2 weeks (n=422). In the STRATOS 1 all-comers population, tralokinumab every 2 weeks did not significantly reduce AAER compared with placebo (7.0% reduction [95% CI -20.8 to 28.4]; rate ratio 0.93 [95% CI 0.72 to 1.21]; p=0.59). Baseline fractional exhaled nitric oxide (FENO) 37 ppb or greater was identified as the preferred biomarker in STRATOS 1; in FENO-high participants, tralokinumab every 2 weeks (n=97) reduced AAER by 44.0% (95% CI 6.0 to 66.0; rate ratio 0.56 [95% CI 0.34 to 0.94]; p=0.028) compared with placebo (n=102). In the STRATOS 2 FENO-high population, tralokinumab every 2 weeks (n=108) did not significantly improve AAER (15.8% reduction [95% CI -33.7 to 47.0]; rate ratio 0.84 [95% CI 0.53 to 1.34]; p=0.47) compared with placebo (n=121). The safety profile was consistent with that of previous tralokinumab trials. INTERPRETATION: Tralokinumab reduced AAER in participants with severe asthma with baseline FENO 37 ppb or higher in STRATOS 1, but not in STRATOS 2. These inconsistent effects on AAER do not support a key role for interleukin 13 in severe asthma exacerbations. FUNDING: AstraZeneca. PMID- 29792289 TI - Combined transarterial chemoembolization and microwave ablation versus transarterial chemoembolization in BCLC stage B hepatocellular carcinoma. AB - PURPOSE: We aimed to compare the clinical effectiveness of combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) with TACE monotherapy in BCLC stage B HCC patients with tumor size <=7 cm and tumor number <=5. METHODS: We retrospectively reviewed 150 BCLC stage B HCC patients who had received TACE monotherapy or TACE-MWA combination therapy in our hospital from March 2007 to April 2016. The patients were matched by propensity score at the ratio of 1:2 by optimal method. The median follow-up period was 16 months. The overall survival, tumor response and progression-free survival were compared between the two groups by Kaplan-Meier method and Log rank test. RESULTS: Tumor response (complete or partial response or stable disease) rates at 6, 12, 18, 24 months were 55.5%, 37.3%, 21.3%, 15.8% for TACE group, and 74%, 47.8%, 35%, 31.8% for TACE-MWA group, respectively. The survival rates at 1, 3, 5 years were 77.5%, 42.1%, 21% for TACE group and 93.1%, 79%, 67.7% for TACE-MWA group, respectively. Compared with TACE group, the TACE-MWA group had significantly improved progression-free survival (P = 0.044) and overall survival (P = 0.002). CONCLUSION: TACE-MWA combination therapy has better clinical effectiveness than TACE monotherapy in BCLC stage B patients with tumor size <=7 cm and tumor number <=5. PMID- 29792290 TI - The Use of Mobile Health Applications to Improve Patient Experience: Cross Sectional Study in Chinese Public Hospitals. AB - BACKGROUND: The proliferation of mobile health apps has greatly changed the way society accesses the health care industry. However, despite the widespread use of mobile health apps by patients in China, there has been little research that evaluates the effect of mobile health apps on patient experience during hospital visits. OBJECTIVE: The purpose of our study was to examine whether the use of mobile health apps improves patient experience and to find out the difference in patient experience between users and nonusers and the characteristics associated with the users of these apps. METHODS: We used the Chinese Outpatient Experience Questionnaire to survey patient experience. A sample of 300 outpatients was randomly selected from 3 comprehensive public hospitals (3 tertiary hospitals) in Hubei province, China. Each hospital randomly selected 50 respondents from mobile health app users and 50 from nonusers. A chi-square test was employed to compare the different categorical characteristics between mobile health app users and nonusers. A t test was used to test the significance in continuous variables between user scores and nonuser scores. Multiple linear regression was conducted to determine whether the use of mobile health apps during hospital visits was associated with patient experience. RESULTS: The users and nonusers differed in age (chi22=12.2, P=.002), education (chi23=9.3, P=.03), living place (chi21=7.7, P=.006), and the need for specialists (chi24=11.0, P=.03). Compared with nonusers, mobile health app users in China were younger, better educated, living in urban areas, and had higher demands for specialists. In addition, mobile health app users gave significantly higher scores than nonusers in total patient experience scores (t298=3.919, P<.001), the 18 items and the 5 dimensions of physician-patient communication (t298=2.93, P=.004), health information (t298=3.556, P<.001), medical service fees (t298=3.991, P<.001), short-term outcome (t298=4.533, P<.001), and general satisfaction (t298=4.304, P<.001). Multiple linear regression results showed that the use of mobile health apps during hospital visits influenced patient experience (t289=3.143, P=.002). After controlling for other factors, it was shown that the use of mobile health apps increased the outpatient experience scores by 17.7%. Additional results from the study found that the self-rated health status (t289=3.746, P<.001) and monthly income of patients (t289=2.416, P=.02) influenced the patient experience as well. CONCLUSIONS: The use of mobile health apps could improve patient experience, especially with regard to accessing health information, making physician-patient communication more convenient, ensuring transparency in medical charge, and ameliorating short-term outcomes. All of these may contribute to positive health outcomes. Therefore, we should encourage the adoption of mobile health apps in health care settings so as to improve patient experience. PMID- 29792291 TI - Diurnal Variations of Depression-Related Health Information Seeking: Case Study in Finland Using Google Trends Data. AB - BACKGROUND: Some of the temporal variations and clock-like rhythms that govern several different health-related behaviors can be traced in near real-time with the help of search engine data. This is especially useful when studying phenomena where little or no traditional data exist. One specific area where traditional data are incomplete is the study of diurnal mood variations, or daily changes in individuals' overall mood state in relation to depression-like symptoms. OBJECTIVE: The objective of this exploratory study was to analyze diurnal variations for interest in depression on the Web to discover hourly patterns of depression interest and help seeking. METHODS: Hourly query volume data for 6 depression-related queries in Finland were downloaded from Google Trends in March 2017. A continuous wavelet transform (CWT) was applied to the hourly data to focus on the diurnal variation. Longer term trends and noise were also eliminated from the data to extract the diurnal variation for each query term. An analysis of variance was conducted to determine the statistical differences between the distributions of each hour. Data were also trichotomized and analyzed in 3 time blocks to make comparisons between different time periods during the day. RESULTS: Search volumes for all depression-related query terms showed a unimodal regular pattern during the 24 hours of the day. All queries feature clear peaks during the nighttime hours around 11 PM to 4 AM and troughs between 5 AM and 10 PM. In the means of the CWT-reconstructed data, the differences in nighttime and daytime interest are evident, with a difference of 37.3 percentage points (pp) for the term "Depression," 33.5 pp for "Masennustesti," 30.6 pp for "Masennus," 12.8 pp for "Depression test," 12.0 pp for "Masennus testi," and 11.8 pp for "Masennus oireet." The trichotomization showed peaks in the first time block (00.00 AM-7.59 AM) for all 6 terms. The search volumes then decreased significantly during the second time block (8.00 AM-3.59 PM) for the terms "Masennus oireet" (P<.001), "Masennus" (P=.001), "Depression" (P=.005), and "Depression test" (P=.004). Higher search volumes for the terms "Masennus" (P=.14), "Masennustesti" (P=.07), and "Depression test" (P=.10) were present between the second and third time blocks. CONCLUSIONS: Help seeking for depression has clear diurnal patterns, with significant rise in depression related query volumes toward the evening and night. Thus, search engine query data support the notion of the evening-worse pattern in diurnal mood variation. Information on the timely nature of depression-related interest on an hourly level could improve the chances for early intervention, which is beneficial for positive health outcomes. PMID- 29792292 TI - Identifying Medication Management Smartphone App Features Suitable for Young Adults With Developmental Disabilities: Delphi Consensus Study. AB - BACKGROUND: Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained. OBJECTIVE: The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus method. METHODS: A compilation of medication management app features was performed by searching the iTunes App Store, United States, in February 2016, using the following terms: adherence, medication, medication management, medication list, and medication reminder. After identifying features within the retrieved apps, a final list of 42 features grouped into 4 modules (medication list, medication reminder, medication administration record, and additional features) was included in a questionnaire for expert consensus rating. A total of 52 experts in developmental disabilities, including persons with developmental disabilities, caregivers, and professionals, were invited to participate in a 3-round Delphi technique. The purpose was to obtain consensus on features that are preferred and suitable to promote independence in the medication management process among persons with developmental disabilities. Consensus for the first, second, and third rounds was defined as >=90%, >=80%, and >=75% agreement, respectively. RESULTS: A total of 75 responses were received over the 3 Delphi rounds-30 in the first round, 24 in the second round, and 21 in the third round. At the end of the third round, cumulative consensus was achieved for 60% (12/20) items in the medication list module, 100% (3/3) in the medication reminder module, 67% (2/3) in the medication administration record module, and 63% (10/16) in the additional features module. In addition to the medication list, medication reminder, and medication administration record features, experts selected the following top 3 most important additional features: automatic refills through pharmacies; ability to share medication information from the app with providers; and ability to share medication information from the app with family, friends, and caregivers. The top 3 least important features included a link to an official drug information source, privacy settings and password protection, and prescription refill reminders. CONCLUSIONS: Although several mobile apps for medication management exist, few are specifically designed to support persons with developmental disabilities in the complex medication management process. Of the 42 different features assessed, 64% (27/42) achieved consensus for inclusion in a future medication management app. This study provides information on the features of a medication management app that are most important to persons with developmental disabilities, caregivers, and professionals. PMID- 29792293 TI - Recruitment and Participation of Recreational Runners in a Large Epidemiological and Genetic Research Study: Retrospective Data Analysis. AB - BACKGROUND: With the increasing capacity for remote collection of both data and samples for medical research, a thorough assessment is needed to determine the association of population characteristics and recruitment methodologies with response rates. OBJECTIVE: The aim of this research was to assess population representativeness in a two-stage study of health and injury in recreational runners, which consisted of an epidemiological arm and genetic analysis. METHODS: The cost and success of various classical and internet-based methods were analyzed, and demographic representativeness was assessed for recruitment to the epidemiological survey, reported willingness to participate in the genetic arm of the study, actual participation, sample return, and approval for biobank storage. RESULTS: A total of 4965 valid responses were received, of which 1664 were deemed eligible for genetic analysis. Younger age showed a negative association with initial recruitment rate, expressed willingness to participate in genetic analysis, and actual participation. Additionally, female sex was associated with higher initial recruitment rates, and ethnic origin impacted willingness to participate in the genetic analysis (all P<.001). CONCLUSIONS: The sharp decline in retention through the different stages of the study in young respondents suggests the necessity to develop specific recruitment and retention strategies when investigating a young, physically active population. PMID- 29792294 TI - Training Working Memory in Adolescents Using Serious Game Elements: Pilot Randomized Controlled Trial. AB - BACKGROUND: Working memory capacity has been found to be impaired in adolescents with various psychological problems, such as addictive behaviors. Training of working memory capacity can lead to significant behavioral improvements, but it is usually long and tedious, taxing participants' motivation to train. OBJECTIVE: This study aimed to evaluate whether adding game elements to the training could help improve adolescents' motivation to train while improving cognition. METHODS: A total of 84 high school students were allocated to a working memory capacity training, a gamified working memory capacity training, or a placebo condition. Working memory capacity, motivation to train, and drinking habits were assessed before and after training. RESULTS: Self-reported evaluations did not show a self reported preference for the game, but participants in the gamified working memory capacity training condition did train significantly longer. The game successfully increased motivation to train, but this effect faded over time. Working memory capacity increased equally in all conditions but did not lead to significantly lower drinking, which may be due to low drinking levels at baseline. CONCLUSIONS: We recommend that future studies attempt to prolong this motivational effect, as it appeared to fade over time. PMID- 29792295 TI - Supply and Demand in mHealth Apps for Persons With Multiple Sclerosis: Systematic Search in App Stores and Scoping Literature Review. AB - BACKGROUND: Multiple sclerosis (MS) is a non-curable chronic inflammatory disease of the central nervous system that affects more than 2 million people worldwide. MS-related symptoms impact negatively on the quality of life of persons with MS, who need to be active in the management of their health. mHealth apps could support these patient groups by offering useful tools, providing reliable information, and monitoring symptoms. A previous study from this group identified needs, barriers, and facilitators for the use of mHealth solutions among persons with MS. It is unknown how commercially available health apps meet these needs. OBJECTIVE: The main objective of this review was to assess how the features present in MS apps meet the reported needs of persons with MS. METHODS: We followed a combination of scoping review methodology and systematic assessment of features and content of mHealth apps. A search strategy was defined for the two most popular app stores (Google Play and Apple App Store) to identify relevant apps. Reviewers independently conducted a screening process to filter apps according to the selection criteria. Interrater reliability was assessed through the Fleiss-Cohen coefficient (k=.885). Data from the included MS apps were extracted and explored according to classification criteria. RESULTS: An initial total of 581 potentially relevant apps was found. After removing duplicates and applying inclusion and exclusion criteria, 30 unique apps were included in the study. A similar number of apps was found in both stores. The majority of the apps dealt with disease management and disease and treatment information. Most apps were developed by small and medium-sized enterprises, followed by pharmaceutical companies. Patient education and personal data management were among the most frequently included features in these apps. Energy management and remote monitoring were often not present in MS apps. Very few contained gamification elements. CONCLUSIONS: Currently available MS apps fail to meet the needs and demands of persons with MS. There is a need for health professionals, researchers, and industry partners to collaborate in the design of mHealth solutions for persons with MS to increase adoption and engagement. PMID- 29792297 TI - Antidepressant induced weight gain. PMID- 29792296 TI - "It's Totally Okay to Be Sad, but Never Lose Hope": Content Analysis of Infertility-Related Videos on YouTube in Relation to Viewer Preferences. AB - BACKGROUND: Infertility patients frequently use the internet to find fertility related information and support from people in similar circumstances. YouTube is increasingly used as a source of health-related information and may influence health decision making. There have been no studies examining the content of infertility-related videos on YouTube. OBJECTIVE: The purpose of this study was to (1) describe the content of highly viewed videos on YouTube related to infertility and (2) identify video characteristics that relate to viewer preference. METHODS: Using the search term "infertility," the 80 top-viewed YouTube videos and their viewing statistics (eg, views, likes, and comments) were collected. Videos that were non-English, unrelated to infertility, or had age restrictions were excluded. Content analysis was used to examine videos, employing a coding rubric that measured the presence or absence of video codes related to purpose, tone, and demographic and fertility characteristics (eg, sex, parity, stage of fertility treatment). RESULTS: A total of 59 videos, with a median of 156,103 views, met the inclusion criteria and were categorized into 35 personal videos (35/59, 59%) and 24 informational-educational videos (24/59, 41%). Personal videos did not differ significantly from informational-educational videos on number of views, dislikes, subscriptions driven, or shares. However, personal videos had significantly more likes (P<.001) and comments (P<.001) than informational-educational videos. The purposes of the videos were treatment outcomes (33/59, 56%), sharing information (30/59, 51%), emotional aspects of infertility (20/59, 34%), and advice to others (6/59, 10%). The tones of the videos were positive (26/59, 44%), neutral (25/59, 42%), and mixed (8/59, 14%); there were no videos with negative tone. No videos contained only male posters. Videos with a positive tone did not differ from neutral videos in number of views, dislikes, subscriptions driven, or shares; however, positive videos had significantly more likes (P<.001) and comments (P<.001) than neutral videos. A majority (21/35, 60%) of posters of personal videos shared a pregnancy announcement. CONCLUSIONS: YouTube is a source of both technical and personal experience-based information about infertility. However, videos that include personal experiences may elicit greater viewer engagement. Positive videos and stories of treatment success may provide hope to viewers but could also create and perpetuate unrealistic expectations about the success rates of fertility treatment. PMID- 29792298 TI - Nanobody-Antigen Conjugates Elicit HPV-Specific Antitumor Immune Responses. AB - High-risk human papillomavirus-associated cancers express viral oncoproteins (e.g., E6 and E7) that induce and maintain the malignant phenotype. The viral origin of these proteins makes them attractive targets for development of a therapeutic vaccine. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APC) can serve as targeted delivery vehicles for antigens attached to them. Such VHHs were shown to induce CD4+ and CD8+ T-cell responses against model antigens conjugated to them via sortase, but antitumor responses had not yet been investigated. Here, we tested the ability of an anti-CD11b VHH (VHHCD11b) to target APCs and serve as the basis for a therapeutic vaccine to induce CD8+ T cell responses against HPV+ tumors. Mice immunized with VHHCD11b conjugated to an H-2Db-restricted immunodominant E7 epitope (E749-57) had more E7-specific CD8+ T cells compared with those immunized with E749-57 peptide alone. These CD8+ T cells acted prophylactically and conferred protection against a subsequent challenge with HPV E7-expressing tumor cells. In a therapeutic setting, VHHCD11b E749-57 vaccination resulted in greater numbers of CD8+ tumor-infiltrating lymphocytes compared with mice receiving E749-57 peptide alone in HPV+ tumor bearing mice, as measured by in vivo noninvasive VHH-based immune-positron emission tomography (immunoPET), which correlated with tumor regression and survival outcome. Together, these results demonstrate that VHHs can serve as a therapeutic cancer vaccine platform for HPV-induced cancers. Cancer Immunol Res; 6(7); 870-80. (c)2018 AACR. PMID- 29792299 TI - A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. AB - BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing. METHODS: Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or noncardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. RESULTS: The derivation cohort included 414 consecutive patients (267 cases with HFpEF and 147 controls; HFpEF prevalence, 64%). The test cohort included 100 consecutive patients (61 with HFpEF; prevalence, 61%). Obesity, atrial fibrillation, age >60 years, treatment with >=2 antihypertensives, echocardiographic E/e' ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mm Hg were selected as the final set of predictive variables. A weighted score based on these 6 variables was used to create a composite score (H2FPEF score) ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI, 1.74-2.30; P<0.0001), with an area under the curve of 0.841 ( P<0.0001). The H2FPEF score was superior to a currently used algorithm based on expert consensus (increase in area under the curve of 0.169; 95% CI, 0.120-0.217; P<0.0001). Performance in the independent test cohort was maintained (area under the curve, 0.886; P<0.0001). CONCLUSIONS: The H2FPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea. PMID- 29792301 TI - Digital clinical encounters. PMID- 29792300 TI - What is the effect of secondary (high) schooling on subsequent medical school performance? A national, UK-based, cohort study. AB - OBJECTIVES: University academic achievement may be inversely related to the performance of the secondary (high) school an entrant attended. Indeed, some medical schools already offer 'grade discounts' to applicants from less well performing schools. However, evidence to guide such policies is lacking. In this study, we analyse a national dataset in order to understand the relationship between the two main predictors of medical school admission in the UK (prior educational attainment (PEA) and performance on the United Kingdom Clinical Aptitude Test (UKCAT)) and subsequent undergraduate knowledge and skills-related outcomes analysed separately. METHODS: The study was based on national selection data and linked medical school outcomes for knowledge and skills-based tests during the first five years of medical school. UKCAT scores and PEA grades were available for 2107 students enrolled at 18 medical schools. Models were developed to investigate the potential mediating role played by a student's previous secondary school's performance. Multilevel models were created to explore the influence of students' secondary schools on undergraduate achievement in medical school. RESULTS: The ability of the UKCAT scores to predict undergraduate academic performance was significantly mediated by PEA in all five years of medical school. Undergraduate achievement was inversely related to secondary school-level performance. This effect waned over time and was less marked for skills, compared with undergraduate knowledge-based outcomes. Thus, the predictive value of secondary school grades was generally dependent on the secondary school in which they were obtained. CONCLUSIONS: The UKCAT scores added some value, above and beyond secondary school achievement, in predicting undergraduate performance, especially in the later years of study. Importantly, the findings suggest that the academic entry criteria should be relaxed for candidates applying from the least well performing secondary schools. In the UK, this would translate into a decrease of approximately one to two A-level grades. PMID- 29792303 TI - Recurrent spontaneous vertigo with interictal headshaking nystagmus. AB - OBJECTIVE: To define a disorder characterized by recurrent spontaneous vertigo (RSV) of unknown etiology and interictal headshaking nystagmus (HSN). METHODS: We characterized HSN in 35 patients with RSV-HSN compared to that recorded in randomly selected patients with compensated vestibular neuritis (VN), vestibular migraine (VM), and Meniere disease (MD). RESULTS: The estimated time constant (TC) of the primary phase of HSN was 12 seconds (95% confidence interval [CI] 12 13) in patients with RSV-HSN, which was larger than those in patients with VN (5 seconds, 95% CI 4-5), VM (5 seconds, 95% CI 5-6), or MD (6 seconds, 95% CI 5-6). TCs of the horizontal vestibulo-ocular reflex were also larger during the rotatory chair test in patients with RSV-HSN. Among the 35 patients with RSV-HSN, 7 showed vigorous long-lasting HSN with a peak slow-phase velocity >50.0 degrees /s. In 5 patients (5 of 7, 71%) with vigorous HSN, HSN could have been induced even with headshaking for only 2 to 5 seconds. Long-term prognosis was favorable, with a resolution or improvement of the symptoms in more than half of the patients during the median follow-up of 12 (range 2-58) years from symptom onset. None developed VM, MD, or cerebellar dysfunction during the follow-up. CONCLUSION: The clinical features and characteristics of HSN in our patients indicate a hyperactive and asymmetric velocity-storage mechanism that gives rise to intermittent attacks of spontaneous vertigo probably when marginal compensation of underlying pathology is disrupted by endogenous or exogenous factors. PMID- 29792304 TI - Description of a new type of benign recurrent vertigo of central origin. PMID- 29792302 TI - Blood Pressure Patterns and Subsequent Coronary Artery Calcification in Women Who Delivered Preterm Births. AB - Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [<37 weeks]; n=777 all term births [>=37 weeks]). Latent mixture modeling identified blood pressure trajectories across 20 years, and these were related to CAC at years 20 and 25. Three systolic blood pressure (SBP) patterns were identified: low stable (n=563; 53%), moderate (n=416; 40%), and moderate increasing (n=70; 7%). Women with moderate-increasing SBP were more likely to have delivered preterm compared with those in the low-stable group (40% versus 21%; P<0.0001), and they were more likely to have CAC (38.5% versus 12.2%). The SBP and CAC association varied by preterm birth (P interaction=0.04). Women with preterm delivery and a moderate increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14-4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49-2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife. PMID- 29792305 TI - Sensory analysis of characterising flavours: evaluating tobacco product odours using an expert panel. AB - OBJECTIVES: Tobacco flavours are an important regulatory concept in several jurisdictions, for example in the USA, Canada and Europe. The European Tobacco Products Directive 2014/40/EU prohibits cigarettes and roll-your-own tobacco having a characterising flavour. This directive defines characterising flavour as 'a clearly noticeable smell or taste other than one of tobacco [...]'. To distinguish between products with and without a characterising flavour, we trained an expert panel to identify characterising flavours by smelling. METHODS: An expert panel (n=18) evaluated the smell of 20 tobacco products using self defined odour attributes, following Quantitative Descriptive Analysis. The panel was trained during 14 attribute training, consensus training and performance monitoring sessions. Products were assessed during six test sessions. Principal component analysis, hierarchical clustering (four and six clusters) and Hotelling's T-tests (95% and 99% CIs) were used to determine differences and similarities between tobacco products based on odour attributes. RESULTS: The final attribute list contained 13 odour descriptors. Panel performance was sufficient after 14 training sessions. Products marketed as unflavoured that formed a cluster were considered reference products. A four-cluster method distinguished cherry-flavoured, vanilla-flavoured and menthol-flavoured products from reference products. Six clusters subdivided reference products into tobacco leaves, roll-your-own and commercial products. CONCLUSIONS: An expert panel was successfully trained to assess characterising odours in cigarettes and roll-your own tobacco. This method could be applied to other product types such as e cigarettes. Regulatory decisions on the choice of reference products and significance level are needed which directly influences the products being assessed as having a characterising odour. PMID- 29792306 TI - Predicting the viscosity of digesta from the physical characteristics of particle suspensions using existing rheological models. AB - The measurement of the viscosity of digesta is complicated by settling and compositional changes that accompany digestion. The current work determined whether the apparent and relative viscosities (etaa and etar) of digesta could be accurately determined from the actual and maximum solid volume fractions (phi and phimax, respectively) using the Maron-Pierce equation. The rheological properties of digesta from the small intestine of six pigs were determined at a shear rate of 1 s-1 at 37 degrees C. A series of suspensions of plant fibre in a Newtonian liquid (70% aqueous fructose) were made at viscosities similar to pig digesta by adjusting phi The relationships between the apparent and relative viscosities (etaa and etar) and the plant fibre properties; aspect ratio (AR) and phi and phimax were then determined for digesta and the suspensions. The ARs for the digesta and plant fibre particles were determined using image analysis of scanning electron micrographs and etaa from rheometric flow curves at 37 degrees C, phi from image analysis and gas pycnometry, and phimax from AR and suspension viscosity. The etar of pig digesta and the test suspensions calculated using the Maron-Pierce equation were, with the exception of two outliers, in proportion with etaa determined using a rheometer, indicating that etar could be successfully predicted from the Maron-Pierce equation. PMID- 29792308 TI - Logical modelling uncovers developmental constraints for primary sex determination of chicken gonads. AB - In the chicken, sex determination relies on a ZZ (male)/ZW (female) chromosomal system, but underlying mechanisms are still not fully understood. The Z-dosage and the dominant W-chromosome hypotheses have been proposed to underlie primary sex determination. We present a modelling approach, which assembles the current knowledge and permits exploration of the regulation of this process in chickens. Relying on published experimental data, we assembled a gene network, which led to a logical model that integrates both the Z-dosage and dominant W hypotheses. This model showed that the sexual fate of chicken gonads results from the resolution of the mutual inhibition between DMRT1 and FOXL2, where the initial amount of DMRT1 product determines the development of the gonads. In this respect, at the initiation step, a W-factor would function as a secondary device, by reducing the amount of DMRT1 in ZW gonads when the sexual fate of the gonad is settled, that is when the SOX9 functional level is established. Developmental constraints that are instrumental in this resolution were identified. These constraints establish qualitative restrictions regarding the relative transcription rates of the genes DMRT1, FOXL2 and HEMGN. Our model further clarified the role of OESTROGEN in maintaining FOXL2 function during ovary development. PMID- 29792307 TI - Putative vaccine candidates and drug targets identified by reverse vaccinology and subtractive genomics approaches to control Haemophilus ducreyi, the causative agent of chancroid. AB - Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi The control of chancroid is difficult and the only current available treatment is antibiotic therapy; however, antibiotic resistance has been reported in endemic areas. Owing to recent outbreaks of STIs worldwide, it is important to keep searching for new treatment strategies and preventive measures. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 28 strains of H. ducreyi We identified 847 non-host homologous proteins, being 332 exposed/secreted/membrane and 515 cytoplasmic proteins. We also checked their essentiality, functionality and virulence. Altogether, we predicted 13 candidate vaccine targets and three drug targets, where two vaccines (A01_1275, ABC transporter substrate-binding protein; and A01_0690, Probable transmembrane protein) and three drug targets (A01_0698, Purine nucleoside phosphorylase; A01_0702, Transcription termination factor; and A01_0677, Fructose-bisphosphate aldolase class II) are harboured by pathogenicity islands. Finally, we applied a molecular docking approach to analyse each drug target and selected ZINC77257029, ZINC43552589 and ZINC67912117 as promising molecules with favourable interactions with the target active site residues. Altogether, the targets identified here may be used in future strategies to control chancroid worldwide. PMID- 29792309 TI - Metabolic and Physiologic Imaging Biomarkers of the Tumor Microenvironment Predict Treatment Outcome with Radiation or a Hypoxia-Activated Prodrug in Mice. AB - Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here, we define two imaging biomarkers that predict differences in tumor response to therapy: (i) partial oxygen pressure (pO2), measured by EPR imaging; and (ii) [1 13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa2, and Su.86.86) were grown in mice. The median pO2 of the mature Hs766t, MiaPaCa2, and Su.86.86 tumors was 9.1 +/- 1.7, 11.1 +/- 2.2, and 17.6 +/- 2.6 mm Hg, and the rate of pyruvate-to-lactate conversion was 2.72 +/- 0.48, 2.28 +/- 0.26, and 1.98 +/- 0.51 per minute, respectively (n = 6, each). These results are in agreement with steady-state data of matabolites quantified by mass spectroscopy and histologic analysis, indicating glycolytic and hypoxia profile in Hs766t, MiaPaca2, and Su.86.86 tumors. Fractionated radiotherapy (5 Gy * 5) resulted in a tumor growth delay of 16.7 +/- 1.6 and 18.0 +/- 2.7 days in MiaPaca2 and Su.86.86 tumors, respectively, compared with 6.3 +/- 2.7 days in hypoxic Hs766t tumors. Treatment with gemcitabine, a first-line chemotherapeutic agent, or the hypoxia activated prodrug TH-302 was more effective against Hs766t tumors (20.0 +/- 3.5 and 25.0 +/- 7.7 days increase in survival time, respectively) than MiaPaCa2 (2.7 +/- 0.4 and 6.7 +/- 0.7 days) and Su.86.86 (4.7 +/- 0.6 and 0.7 +/- 0.6 days) tumors. Collectively, these results demonstrate the ability of molecular imaging biomarkers to predict the response of PDAC to treatment with radiotherapy and TH 302.Significance: pO2 imaging data and clinically available metabolic imaging data provide useful insight into predicting the treatment efficacy of chemotherapy, radiation, and a hypoxia-activated prodrug as monotherapies and combination therapies in PDAC tumor xenograft models. Cancer Res; 78(14); 3783 92. (c)2018 AACR. PMID- 29792310 TI - BET Inhibition Overcomes Receptor Tyrosine Kinase-Mediated Cetuximab Resistance in HNSCC. AB - Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK. Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models. We hypothesized that, in HNSCC, targeting BRD4 could overcome cetuximab resistance by depleting alternative RTK expression. We generated independent models of cetuximab resistance in HNSCC cell lines and interrogated their RTK and BRD4 expression profiles. Cetuximab-resistant clones displayed increased expression and activation of several RTK, such as MET and AXL, as well as an increased percentage of BRD4-expressing cells. Both genetic and pharmacologic inhibition of BRD4 abrogated cell viability in models of acquired and intrinsic cetuximab resistance and was associated with a robust decrease in alternative RTK expression by cetuximab. Combined treatment with cetuximab and bromodomain inhibitor JQ1 significantly delayed acquired resistance and RTK upregulation in patient-derived xenograft models of HNSCC. These findings indicate that the combination of cetuximab and bromodomain inhibition may be a promising therapeutic strategy for patients with HNSCC.Significance: Inhibition of bromodomain protein BRD4 represents a potential therapeutic strategy to circumvent the toxicities and financial burden of targeting the multiple receptor tyrosine kinases that drive cetuximab resistance in HNSCC and NSCLC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4331/F1.large.jpg Cancer Res; 78(15); 4331-43. (c)2018 AACR. PMID- 29792312 TI - Identification of patients with hemoglobin SS/Sbeta0 thalassemia disease and pain crises within electronic health records. AB - Electronic health records (EHRs) are a source of big data that provide opportunities for conducting population-based studies and creating learning health systems, especially for rare conditions such as sickle cell disease (SCD). The objective of our study is to validate algorithms for accurate identification of patients with hemoglobin (Hb) SS/Sbeta0 thalassemia and acute care encounters for pain among SCD patients within EHR warehouse. We used data for children receiving care at Children's Hospital of Wisconsin from 2013 to 2016 to test the accuracy of the 2 algorithms. The algorithm for genotype identification used composite information (blood test results, transcranial Doppler) along with diagnoses codes. Acute pain encounters were identified using diagnoses codes and further refined by using prescription of IV pain medications. Sensitivities and specificities were calculated for the algorithms. Predictive values for the algorithm to identify SCD genotype were calculated. For all assessments, the local SCD registry and patients' charts were considered gold standards. These included 360 children with SCD, of whom 51% were females. Our algorithm to identify patients with HbSS/Sbeta0 thalassemia demonstrated sensitivity of 89.9% (confidence interval [CI], 85.1%-93.7%) and specificity of 97.1% (CI, 92.7% 99.2%). This algorithm had a positive and negative predictive value of 97.9% (CI, 94.8%-99.9%) and 88.7% (CI, 82.6%-93.3%), respectively. Acute pain crises encounters were identified with a sensitivity and specificity of 95.1% (CI, 86.3% 99.0%) and 96.1% (CI, 88.3%-99.6%). This study demonstrates the feasibility to accurately identify patients with specific types of SCD and pain crises within an EHR. PMID- 29792313 TI - 65 YEARS OF THE DOUBLE HELIX: One gene, many endocrine and metabolic syndromes: PTEN-opathies and precision medicine. AB - An average of 10% of all cancers (range 1-40%) are caused by heritable mutations and over the years have become powerful models for precision medicine practice. Furthermore, such cancer predisposition genes for seemingly rare syndromes have turned out to help explain mechanisms of sporadic carcinogenesis and often inform normal development. The tumor suppressor PTEN encodes a ubiquitously expressed phosphatase that counteracts the PI3K/AKT/mTOR cascade - one of the most critical growth-promoting signaling pathways. Clinically, individuals with germline PTEN mutations have diverse phenotypes and fall under the umbrella term PTEN hamartoma tumor syndrome (PHTS). PHTS encompasses four clinically distinct allelic overgrowth syndromes, namely Cowden, Bannayan-Riley-Ruvalcaba, Proteus and Proteus-like syndromes. Relatedly, mutations in other genes encoding components of the PI3K/AKT/mTOR pathway downstream of PTEN also predispose patients to partially overlapping clinical manifestations, with similar effects as PTEN malfunction. We refer to these syndromes as 'PTEN-opathies.' As a tumor suppressor and key regulator of normal development, PTEN dysfunction can cause a spectrum of phenotypes including benign overgrowths, malignancies, metabolic and neurodevelopmental disorders. Relevant to clinical practice, the identification of PTEN mutations in patients not only establishes a PHTS molecular diagnosis, but also informs on more accurate cancer risk assessment and medical management of those patients and affected family members. Importantly, timely diagnosis is key, as early recognition allows for preventative measures such as high-risk screening and surveillance even prior to cancer onset. This review highlights the translational impact that the discovery of PTEN has had on the diagnosis, management and treatment of PHTS. PMID- 29792311 TI - PEDF regulates plasticity of a novel lipid-MTOC axis in prostate cancer associated fibroblasts. AB - Prostate tumors make metabolic adaptations to ensure adequate energy and amplify cell cycle regulators, such as centrosomes, to sustain their proliferative capacity. It is not known whether cancer-associated fibroblasts (CAFs) undergo metabolic re-programming. We postulated that CAFs augment lipid storage and amplify centrosomal or non-centrosomal microtubule-organizing centers (MTOCs) through a pigment epithelium-derived factor (PEDF)-dependent lipid-MTOC signaling axis. Primary human normal prostate fibroblasts (NFs) and CAFs were evaluated for lipid content, triacylglycerol-regulating proteins, MTOC number and distribution. CAFs were found to store more neutral lipids than NFs. Adipose triglyceride lipase (ATGL) and PEDF were strongly expressed in NFs, whereas CAFs had minimal to undetectable levels of PEDF or ATGL protein. At baseline, CAFs demonstrated MTOC amplification when compared to 1-2 perinuclear MTOCs consistently observed in NFs. Treatment with PEDF or blockade of lipogenesis suppressed lipid content and MTOC number. In summary, our data support that CAFs have acquired a tumor like phenotype by re-programming lipid metabolism and amplifying MTOCs. Normalization of MTOCs by restoring PEDF or by blocking lipogenesis highlights a previously unrecognized plasticity in centrosomes, which is regulated through a new lipid-MTOC axis.This article has an associated First Person interview with the first author of the paper. PMID- 29792316 TI - Chemoresponsive Nanofluidic Pump That Turns Off in the Presence of Lead Ion. AB - There are many applications that require the integration of a pump and a chemical sensor so that the solution being pumped can be analyzed in real time for a specific chemical species and the flow adjusted according to the measured concentration of that species. We describe here an alternative strategy: a chemoresponsive pump where a single device acts as both the sensor and pump simultaneously. We demonstrate this concept with a nanofluidic Pb2+-responsive pump that uses electroosmotic flow as the pumping technology, and a Pb2+-binding ionophore that allows the device to selectively respond to Pb2+. The pump yields high flow rates at low Pb2+ concentrations (<1 MUM), but flow rate decreases with concentrations above this threshold and ultimately goes to zero at concentrations above 100 MUM. PMID- 29792317 TI - In Situ Reduction from Uranyl Ion into a Tetravalent Uranium Trimer and Hexamer Featuring Ion-Exchange Properties and the Alexandrite Effect. AB - By utilizing zinc amalgam as an in situ reductant and pH regulator, mild hydrothermal reaction between UO2(CH3COO)2.2H2O, H2SO4, and Cs2CO3 or between UO2(CH3COO)2.2H2O, C2H4(SO3H)2, and K2CO3 yielded a novel cesium UIV sulfate trimer Cs4[U3O(SO4)7].2.2H2O (1) and a new potassium UIV disulfonic hexamer K[U6O4(OH)5(H2O)5][C2H4(SO3)2]6.6H2O (2), respectively. Compound 1 features a lamellar structure with a honeycomb lattice, and it represents an unprecedented trimeric UIV cluster composed of purely inorganic moieties. Complex 2 is built from hexanuclear U4+ cores and K+ ions interconnected by MU5-[C2H4(SO3)2]2- groups, leading to the construction of an extended framework rather than commonly observed discrete, neutral molecular sulfonate clusters. The various binding modes of the sulfate and disulfonate groups, especially the multidentate ones, enable additional bridging between metal ions, which promotes oligomerization and isolation of polynuclear species. Furthermore, compound 1 exhibits both ion exchange properties and the Alexandrite effect, and it is the second example of a uranium complex without chromic functional ligands displaying the latter feature. PMID- 29792318 TI - Condensed Tannin Reacts with SO2 during Wine Aging, Yielding Flavan-3-ol Sulfonates. AB - Numerous monomeric and oligomeric flavanol sulfonation products were observed in 10 wines. Levels of 0.85-20.06 and 0-14.72 mg/L were quantified for two monomeric sulfonated flavan-3-ols and, surprisingly, were generally higher than the well known native flavan-3-ol monomers. Increasing SO2 levels during wine aging increased the sulfonate-modified flavan-3-ol monomers and dimers along with higher concentrations of native monomers. The results indicate that >10% of SO2 is reacting with the C-4 carbocation, formed from acid cleavage of the interflavan bond, perhaps by a bimolecular SN2-type reaction, and as a reducing agent. In addition, the high SO2 wine had the lowest protein-binding tannin levels, tannin activity, and mean degree of polymerization (mDP), and acidic SO2 treatment of condensed tannin abolishes protein binding. Thus, SO2 changes tannin composition during wine aging, and the substantial formation of sulfonate modified flavan-3-ols may provide an additional explanation for the reduction in astringency of aged red wines. PMID- 29792315 TI - Genomic Variation Among and Within Six Juglans Species. AB - Genomic analysis in Juglans (walnuts) is expected to transform the breeding and agricultural production of both nuts and lumber. To that end, we report here the determination of reference sequences for six additional relatives of Juglans regia: Juglans sigillata (also from section Dioscaryon), Juglans nigra, Juglans microcarpa, Juglans hindsii (from section Rhysocaryon), Juglans cathayensis (from section Cardiocaryon), and the closely related Pterocarya stenoptera While these are 'draft' genomes, ranging in size between 640Mbp and 990Mbp, their contiguities and accuracies can support powerful annotations of genomic variation that are often the foundation of new avenues of research and breeding. We annotated nucleotide divergence and synteny by creating complete pairwise alignments of each reference genome to the remaining six. In addition, we have re sequenced a sample of accessions from four Juglans species (including regia). The variation discovered in these surveys comprises a critical resource for experimentation and breeding, as well as a solid complementary annotation. To demonstrate the potential of these resources the structural and sequence variation in and around the polyphenol oxidase loci, PPO1 and PPO2 were investigated. As reported for other seed crops variation in this gene is implicated in the domestication of walnuts. The apparently Juglandaceae specific PPO1 duplicate shows accelerated divergence and an excess of amino acid replacement on the lineage leading to accessions of the domesticated nut crop species, Juglans regia and sigillata. PMID- 29792319 TI - Metal-Polydopamine Framework as an Effective Fluorescent Quencher for Highly Sensitive Detection of Hg(II) and Ag(I) Ions through Exonuclease III Activity. AB - In this paper, we propose a metal-polydopamine (MPDA) framework with a specific molecular probe which appears to be the most promising approach to a strong fluorescence quencher. The MPDA framework quenching ability toward various organic fluorophore such as aminoethylcoumarin acetate, 6-carboxyfluorescein (FAM), carboxyteramethylrhodamine, and Cy5 are used to establish a fluorescent biosensor that can selectively recognize Hg2+ and Ag+ ions. The fluorescent quenching efficiency was sufficient to achieve more than 96%. The MPDA framework also exhibits different affinities with ssDNA and dsDNA. In addition, the FAM labeled ssDNA was adsorbed onto the MPDA framework, based on their interaction with the complex formed between MPDA frameworks/ssDNA taken as a sensing platform. By taking advantage of this sensor, highly sensitive and selective determination of Hg2+ and Ag+ ions is achieved through exonuclease III signal amplification activity. The detection limits of Hg2+ and Ag+ achieved to be 1.3 and 34 pM, respectively, were compared to co-existing metal ions and graphene oxide-based sensors. Furthermore, the potential applications of this study establish the highly sensitive fluorescence detection targets in environmental and biological fields. PMID- 29792320 TI - Modular Cavities: Induced Fit of Polar and Apolar Guests into Halogen-Based Receptors. AB - Neutral triangular macrocyclic compounds, [PdX2(4,7-phen)]3.(DMF)3.Et2O (X = Cl, Br; 4,7-phen = 4,7-phenanthroline; DMF = N, N'-dimethylformamide; Et2O = diethyl ether), were synthesized, and their molecular structures were characterized. Solution-state 1H NMR results suggested the formation of metal-ligand bonds, and single-crystal X-ray crystallography revealed clear triangular structures. A detailed examination of the structures indicated the formation of two kinds of cavities in the solid state, where a triangular unit works as a halogen-based receptor for polar and apolar solvents through weak hydrogen-bonding and dipole dipole interaction. PMID- 29792321 TI - Explanation of Dramatic pH-Dependence of Hydrogen Binding on Noble Metal Electrode: Greatly Weakened Water Adsorption at High pH. AB - Hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER) are both 2 orders slower in alkaline electrolyte than in acidic electrolyte, but no explanation has been provided. The first step toward understanding this dramatic pH-dependent HOR/HER performance is to explain the pH-dependent hydrogen binding to the electrode, a perplexing behavior observed experimentally. In this work, we carried out Quantum Mechanics Molecular Dynamics (QMMD) with explicit considerations of solvent and applied voltage ( U) to in situ simulate water/Pt(100) interface in the condition of under-potential adsorption of hydrogen ( HUPD). We found that as U is made more negative, the electrode tends to repel water, which in turn increases the hydrogen binding. We predicted a 0.13 eV increase in hydrogen binding from pH = 0.2 to pH = 12.8 with a slope of 10 meV/pH, which is close to the experimental observation of 8 to 12 meV/pH. Thus, we conclude that the changes in water adsorption are the major causes of pH dependent hydrogen binding on a noble metal. The new insight of critical role of surface water in modifying electrochemical reactions provides a guideline in designing HER/HOR catalyst targeting for the alkaline electrolyte. PMID- 29792322 TI - Metabolism of Phenolic Compounds in LPS-stimulated Raw264.7 Cells Can Impact Their Anti-inflammatory efficacy: Indication of Hesperetin. AB - Raw264.7 is a murine macrophage-like cell line commonly used to study the anti inflammatory efficacy of natural compounds. However, the impacts of long-time incubation on the tested compounds are often inappropriately ignored. Among 77 natural phenolic compounds (mainly flavonoids), only 36 remain more than 70% after a 15-h incubation in cell culture medium at 37 degrees C. Interestingly, for those compounds with a relatively good chemical stability, the presence of Raw264.7 cells could accelerate their disappearance in the medium, indicating that cellular metabolism occurred. As a representative phenolic, hesperetin was found to be efficiently metabolized by Raw264.7 cells and the metabolite was identified as a glucuronide in the further investigation. The glucuronidation activity is constitutive in this cell line. At certain concentration levels of hesperetin, the ability of hesperetin to inhibit PGD2 production in LPS-induced Raw264.7 cells was significantly enhanced by introducing beta-glucuronidase, which can hydrolyze hesperetin glucuronide, into the incubation medium. The results indicate that glucuronidation and excretion of hesperetin can significantly impact its bioactivity in Raw264.7 cells. PMID- 29792323 TI - Cellular-Beacon-Mediated Counting for the Ultrasensitive Detection of Ebola Virus on an Integrated Micromagnetic Platform. AB - Ebola virus (EBOV) disease is a complex zoonosis that is highly virulent in humans and has caused many deaths. Highly sensitive detection of EBOV is of great importance for early-stage diagnosis for increasing the probability of survival. Herein, we established a cellular-beacon-mediated counting strategy for an ultrasensitive EBOV assay on a micromagnetic platform. The detection platform, which was assisted by on-demand magnetic-field manipulation, showed high integration and enhanced complex-sample pretreatment by magnetophoretic separation and continuous-flow washing. Cellular beacons (i.e., fluorescent cells) with superior optical properties were used as reporters, and each cellular beacon was used as a fluorescent tracking unit to quantify EBOV by counting the numbers of individual fluorescent signals on the micromagnetic platform. This method achieves high sensitivity with a detection limit as low as 2.6 pg/mL, and the detection limit shows little difference in a complex matrix. In addition, it has excellent specificity and good reproducibility. These results indicate that this method proposes an ultrasensitive detection strategy for early diagnosis of the disease. PMID- 29792324 TI - Photochemical Formation and Transformation of Birnessite: Effects of Cations on Micromorphology and Crystal Structure. AB - As important components with excellent oxidation and adsorption activity in soils and sediments, manganese oxides affect the transportation and fate of nutrients and pollutants in natural environments. In this work, birnessite was formed by photocatalytic oxidation of Mn2+aq in the presence of nitrate under solar irradiation. The effects of concentrations and species of interlayer cations (Na+, Mg2+, and K+) on birnessite crystal structure and micromorphology were investigated. The roles of adsorbed Mn2+ and pH in the transformation of the photosynthetic birnessite were further studied. The results indicated that Mn2+aq was oxidized to birnessite by superoxide radicals (O2*-) generated from the photolysis of NO3- under UV irradiation. The particle size and thickness of birnessite decreased with increasing cation concentration. The birnessite showed a plate-like morphology in the presence of K+, while exhibited a rumpled sheet like morphology when Na+ or Mg2+ was used. The different micromorphologies of birnessites could be ascribed to the position of cations in the interlayer. The adsorbed Mn2+ and high pH facilitated the reduction of birnessite to low-valence manganese oxides including hausmannite, feitknechtite, and manganite. This study suggests that interlayer cations and Mn2+ play essential roles in the photochemical formation and transformation of birnessite in aqueous environments. PMID- 29792325 TI - Non-geminal Aliphatic Dihalogenation Pattern in Dichlorinated Diaporthins from Hamigera fusca NRRL 35721. AB - Two new epimeric dihalogenated diaporthins, (9 R *)-8-methyl-9,11 dichlorodiaporthin (2) and (9 S *)-8-methyl-9,11-dichlorodiaporthin (3), have been isolated from the soil fungus Hamigera fusca NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (1). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds 1-3 are the first isocoumarins and the first halogenated metabolites ever reported from the Hamigera genus. The new compounds 2 and 3 display a non-geminal aliphatic dichlorination pattern unprecedented among known fungal dihalogenated aromatic polyketides. A bifunctional methyltransferase/aliphatic halogenase flavoenzyme is proposed to be involved in the biosynthesis of dichlorinated diaporthins 1-3. These metabolites are weakly cytotoxic. PMID- 29792326 TI - Common Principles of Molecular Electronics and Nanoscale Electrochemistry. AB - The merging of nanoscale electronics and electrochemistry can potentially modernize the way electronic devices are currently engineered or constructed. This Feature offers a conceptual discussion of this central topic, with particular focus on the impact that uniting physical and chemical concepts at the nanoscale could have on the future development of electroanalytical devices. PMID- 29792327 TI - Multifunctional Binary Monolayers Ge xP y: Tunable Band Gap, Ferromagnetism, and Photocatalyst for Water Splitting. AB - The most stable structures of two-dimensional Ge xP y and Ge xAs y monolayers with different stoichiometries (e.g., GeP, GeP2, and GeP3) are explored systematically through the combination of the particle-swarm optimization technique and density functional theory optimization. For GeP3, we show that the newly predicted most stable C2/ m structure is 0.16 eV/atom lower in energy than the state-of-the-art P3m1 structure reported previously ( Nano Lett. 2017, 17, 1833). The computed electronic band structures suggest that all the stable and metastable monolayers of Ge xP y are semiconductors with highly tunable band gaps under the biaxial strain, allowing strain engineering of their band gaps within nearly the whole visible-light range. More interestingly, the hole doping can convert the C2/ m GeP3 monolayer from nonmagnetic to ferromagnetic because of its unique valence band structure. For the GeP2 monolayer, the predicted most stable Pmc21 structure is a (quasi) direct-gap semiconductor that possesses a high electron mobility of ~800 cm2 V-1 s-1 along the k a direction, which is much higher than that of MoS2 (~200 cm2 V-1 s-1). More importantly, the Pmc21 GeP2 monolayer not only can serve as an n-type channel material in field-effect transistors but also can be an effective catalyst for splitting water. PMID- 29792328 TI - Transforming Nanofibers into Woven Nanotextiles for Vascular Application. AB - This study investigates the unique properties, fabrication technique, and vascular applications of woven nanotextiles made from low-strength nanoyarns, which are bundles of thousands of nanofibers. An innovative robotic system was developed to meticulously interweave nanoyarns in longitudinal and transverse directions, resulting in a flexible, but strong woven product. This is the only technique for producing seamless nanotextiles in tubular form from nanofibers. The porosity and the mechanical properties of nanotextiles could be substantially tuned by altering the number of nanoyarns per unit area. Investigations of the physical and biological properties of the woven nanotextile revealed remarkable and fundamental differences from its nonwoven nanofibrous form and conventional textiles. This enhancement in the material property was attributed to the multitude of hierarchically arranged nanofibers in the woven nanotextiles. This patterned woven nanotextile architecture leads to a superhydrophilic behavior in an otherwise hydrophobic material, which in turn contributed to enhanced protein adsorption and consequent cell attachment and spreading. Short-term in vivo testing was performed, which proved that the nanotextile conduit was robust, suturable, kink proof, and nonthrombogenic and could act as an efficient embolizer when deployed into an artery. PMID- 29792329 TI - Residual Complexity Does Impact Organic Chemistry and Drug Discovery: The Case of Rufomyazine and Rufomycin. AB - Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13C (1.1%) can be highly relevant and calls for advanced analytical characterization of drug leads with extended molar dynamic ranges of >1:1,000 using qNMR and LC-MS. Isolated from an actinomycete strain, 6 was originally found to be active against Mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) of 2 MUg/mL and high selectivity. As a part of lead validation, the dipeptide was synthesized and surprisingly found to be inactive. The initially observed activity was eventually attributed to a very minor contamination (0.24% [m/m]) with a highly active cyclic peptide (MIC ~ 0.02 MUM), subsequently identified as an analogue of 7. This study illustrates the serious implications RC can exert on organic chemistry and drug discovery, and what efforts are vital to improve lead validation and efficiency, especially in NP-related drug discovery programs. PMID- 29792330 TI - Vancomycin Determination by Disrupting Electron-Transfer in a Fluorescence Turn On Squaraine-Anthraquinone Triad. AB - A highly sensitive and selective probe for Vancomycin (Van) in aqueous and serum samples is developed in this study. The probe is based on a triad consisting of a near-infrared squaraine dye (Seta-640) conjugated to two anthraquinone molecules via Lys-d-Ala-d-Ala peptides. In the absence of Van, the close proximity and efficient electron-transfer from the excited Seta-640 dye to anthraquinone result in significant fluorescence quenching of the dye ("off"-state). When Van is added, the antibiotic molecules bind with high affinity to the -d-Ala-d-Ala ligands in a 2:1 stoichiometry (Van:triad), resulting in fluorescence recovery that is as high as 30 times ("on"-state). Even though bound Van enhances the fluorescence by reducing the rate of (intrinsic) polarity-induced nonradiative decay process, this effect plays only a minor role. Instead, the main reason behind the observed fluorescence recovery after drug binding is the effective inhibition of electron-transfer; plausibly arising from a steric-induced lengthening of the spatial separation between electron donor and acceptor. The probe has detection limits of 7.0 and 96.9 nM in buffer and human serum, respectively, operates in the clinically relevant range, is insensitive to Van crystalline degradation product (CDP-1), and is easy to operate by using a commonly available fluorescence spectrometer. PMID- 29792331 TI - Predictable Particle Engineering: Programming the Energy Level, Carrier Generation, and Conductivity of Core-Shell Particles. AB - Core-shell structures are of particular interest in the development of advanced composite materials as they can efficiently bring different components together at nanoscale. The advantage of this structure greatly relies on the crucial design of both core and shell, thus achieving an intercomponent synergistic effect. In this report, we show that decorating semiconductor nanocrystals with a boronate polymer shell can easily achieve programmable core-shell interactions. Taking ZnO and anatase TiO2 nanocrystals as inner core examples, the effective core-shell interactions can narrow the band gap of semiconductor nanocrystals, change the HOMO and LUMO levels of boronate polymer shell, and significantly improve the carrier density of core-shell particles. The hole mobility of core shell particles can be improved by almost 9 orders of magnitude in comparison with net boronate polymer, while the conductivity of core-shell particles is at most 30-fold of nanocrystals. The particle engineering strategy is based on two driving forces: catechol-surface binding and B-N dative bonding and having a high ability to control and predict the shell thickness. Also, this approach is applicable to various inorganic nanoparticles with different components, sizes, and shapes. PMID- 29792332 TI - Ligation-Enhanced pi-Hole...pi Interactions Involving Isocyanides: Effect of pi Hole...pi Noncovalent Bonding on Conformational Stabilization of Acyclic Diaminocarbene Ligands. AB - The reaction of cis-[PdCl2(CNXyl)2] (Xyl = 2,6-Me2C6H3) with the aminoazoles [1 H imidazol-2-amine (1), 4 H-1,2,4-triazol-3-amine (2), 1 H-tetrazol-5-amine (3), 1 H-benzimidazol-2-amine (4), 1-alkyl-1 H-benzimidazol-2-amines, where alkyl = Me (5), Et (6)] in a 2:1 ratio in the presence of a base in CHCl3 at RT proceeds regioselectively and leads to the binuclear diaminocarbene complexes [(ClPdCNXyl)2{MU-C(N-azolyl)N(Xyl)C?NXyl}] (7-12; 73-91%). Compounds 7-12 were characterized by C, H, N elemental analyses, high-resolution ESI+-MS, Fourier transform infrared spectroscopy, 1D (1H, 13C) and 2D (1H,1H-COSY, 1H,1H-NOESY, 1H,13C-HSQC, 1H,13C-HMBC) NMR spectroscopies, and X-ray diffraction (XRDn). Inspection of the XRDn data and results of the Hirshfeld surface analysis suggest the presence in all six structures of intramolecular pi-holeisocyanide...piarene interactions between the electrophilic C atom of the isocyanide moiety and the neighboring arene ring. These interactions also result in distortion of the Pd C=N-Xyl fragment from the linearity. Results of density functional theory calculations [M06/MWB28 (Pd) and 6-31G* (other atoms) level of theory] for model structures of 7-9 followed by the topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method) reveal the presence of these weak interactions also in a CHCl3 solution, and their calculated strength is 1.9-2.2 kcal/mol. The natural bond orbital analysis of 7-9 revealed that pi(C-C)Xyl -> pi*(C-N)isocyanide charge transfer (CT) takes place along with the intramolecular pi-holeisocyanide...piarene interactions. The observed pi(C-C)Xyl -> pi*(C-N)isocyanide CT is due to ligation of the isocyanide to the metal center, whereas in the cases of the uncomplexed p-CNC6H4NC and CNXyl species, the effects of CT are negligible. Available CCDC data were processed from the perspective of isocyanide-involving pi-hole...pi interactions, disclosed the role of metal coordination in the pi-hole donor ability of isocyanides, and verified the pi-holeisocyanide...piarene interaction effect on the stabilization of the in-conformation in metal-bound acyclic diaminocarbenes. PMID- 29792333 TI - Characterization of a Scalable Donor-Based Singlet-Triplet Qubit Architecture in Silicon. AB - We present a donor-based quadruple-quantum-dot device, designed to host two singlet-triplet qubits fabricated by scanning tunnelling microscope lithography, with just two leads per qubit. The design is geometrically compact, with each pair of dots independently controlled via one gate and one reservoir. The reservoirs both supply electrons for the dots and measure the singlet-triplet state of each qubit via dispersive sensing. We verify the locations of the four phosphorus donor dots via an electrostatic model of the device. We study one of the observed singlet-triplet states with a tunnel coupling of 39 GHz and a S0-to- T- decay of 2 ms at zero detuning. We measure a 5 GHz electrostatic interaction between two pairs of dots separated by 65 nm. The results outline a low-gate density pathway to a scalable 1D building block of atomic-precision singlet triplet qubits using donors with dispersive readout. PMID- 29792334 TI - Chemical constituents from Dendrobium hainanense. AB - A new phenolic derivative (1) and a new dihydrophenanthrene (2) were isolated from the aerial part of Dendrobium hainanense rofe, along with 12 known compounds. The structures of the new compounds were elucidated by spectroscopic analysis,and the relative configuration of compound 1 was determined by J-based configuration analysis (JBCA) method. Bioassay result indicated that compound 1 exhibited weak antibacterial activity against Canidia albicans and Ralstonia solanaceanum. PMID- 29792335 TI - Synthesis of novel thymol derivatives against MRSA and ESBL producing pathogenic bacteria. AB - Twelve substituted aryl-azo-thymol derivatives (4a to 4 l) were synthesized and characterized by several spectral techniques such as, FTIR, UV-vis, proton NMR, Mass spectrometry and elemental analysis. Antimicrobial activities were evaluated by agar-well diffusion method against isolated MRSA, ESBL-producing pathogenic bacteria and antifungal resistant fungi, in vitro. In addition, drug likeness properties of derivatives were assessed through bioinformatic tools such as, PASS prediction, molecular docking and Lipinski rules of five, along with determination of toxic nature and LD50 values. Among 12 derivatives, 4a, 4b, 4c, 4 g, 4i, 4j and 4 k had significant antibacterial and antifungal activities with minimum inhibitory concentration values, 40 to 80 MUg/ml. Moreover, the docking scores of derivatives were -8.27 to -11.44 kcal/mol, against 4 bacterial targets and -9.45 to -12.49 kcal/mol against 2 fungal targets. Thus, from in vitro and in silico studies, thymol derivatives had control of MRSA, ESBL-producing bacteria and antifungal resistant fungi. PMID- 29792336 TI - Evaluation of a national neurosurgical formative examination: the UK experience. AB - INTRODUCTION: Formative assessment is a key component in medical education and that it is a helpful process for all involved. Until recently there was no national formative examination for neurosurgical trainees. The Neurosurgery Annual in Training Examination (NAiTE) is an annual online, formative assessment that was introduced in 2014. In this paper, we seek to discuss how well NAiTE relates to established educational practice and principles and its fitness for purpose by discussing its rationale, structure and utility. METHODS: A national online examination was introduced in 2014. The NAiTE consists of 100 single best answer multiple choice questions. The examination and questions with were reviewed and the global results presented. The existing literature and educational theory are used to guide subjective assessment of the process. RESULTS: In 2016, 191 candidates participated in the NAiTE, of whom 154 were trainees working in UK neurosurgical units. The mean score for early stage UK trainees (years 1-3) was 52.4%, intermediate (years 4-5) 58.5% and senior (years 6-8) 65.4%. The NAiTE was found to be a reliable (Cronbach-Alpha of 0.89) and valid assessment of trainees with scores approximating those attained in the Intercollegiate Specialty Examination itself. DISCUSSION: Potential areas for improvement are highlighted, including reference to some that have already been implemented. CONCLUSION: Overall, the examination is a cheap, viable and reliable means of testing trainees and encouraging their onward development and learning as they work towards the Intercollegiate Specialty Examination. PMID- 29792337 TI - Titanium dioxide nanoparticles induce in vitro autophagy. AB - AIM: Concerns about the possible toxicity to environment and human health of titanium dioxide nanoparticles (TiO2 NPs) are increasing. The aim of this study was to investigate the relationship between toxicology and autophage in vitro. METHODS: RAW 264.7 cells were exposed to five concentrations (50, 100, 200, 300, and 400 MUg/mL) and two particle size of TiO2 NPs (30 and 100 nm) for 24 h. RESULTS: The results showed that TiO2 NPs decreased cell viability, phagocytic rate, and phagocytic index in a concentration-dependent manner, thereby inducing autophagy. TiO2 NPs-induced autophagy was indicated by monodansyl cadaverine staining and transmission electron microscopy. TiO2 NPs-induced messenger RNA expression of autophagy-related proteins LC3 and Beclin-1 was also significantly increased compared with those of the unexposed control cells. LC3 and Beclin-1 protein expression levels were markedly increased with the increase of TiO2 NPs concentrations. CONCLUSION: These results suggest the possibility that TiO2 NPs induced toxicology probably plays a key role in autophagy in RAW 264.7 cells, and further exhaustive research on the harmful effects of these NPs in relevant organisms is needed for their safe application. PMID- 29792338 TI - Molecular mechanism for the influence of gender dimorphism on alcoholic liver injury in mice. AB - It is known that women develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. However, the detailed molecular mechanisms remain unclear. The precise mechanism responsible for the sex difference needs to be determined. Female and male mice were given ethanol by intragastric infusion every day for 4 weeks. The pathological changes were detected by hematoxylin-eosin, Sirius red, oil red O, periodic acid-Schiff, and Hochest33258 staining in the liver of female and male mice. The related gene and protein expression of hepatocytes stress, proliferation and apoptosis, glycogen synthesis, lipid metabolism, and hepatic fibrosis were also systematically analyzed in the female and male mice. Livers from ethanol-treated female mice had more serious hepatocyte necrosis, liver fibrosis ( P < 0.01), substantial micro/macrovesicular steatosis ( p < 0.01), glycogen consumption ( p < 0.05), and hepatocytes apoptosis ( p < 0.05) than ethanol-treated male mice. The expression of heat shock protein 27 (HSP27), HSP70, proliferating cell nuclear antigen, B cell lymphoma/leukemia-2 (Bcl-2), and phosphorylated signal transducer and activators of transcription 3 (p-STAT3) was higher in ethanol-treated male mice than ethanol-treated female mice ( P < 0.05 or P < 0.01). But, the expression of Bax (Bcl-2-associated X protein), Caspase 3, CYP2E1 (cytochrome P4502E1), and transforming growth factor betal had the contrary results. Our study suggested that ethanol treatment induced more expression of HSP27 and HSP70, faster hepatocyte proliferation, higher level of glycogen, and interleukin-6 signaling pathway activation, but less hepatocyte apoptosis and CYP2E1 expression in male mice than female mice, which could be helpful to understand the molecular mechanism for the influence of sex difference on alcoholic liver injury. PMID- 29792340 TI - Multidisciplinary care model for HIV improves treatment outcome: a single-centre experience from the Middle East. AB - Multidisciplinary team (MDT) care models have been shown to improve clinical outcomes among HIV patients. We aim to assess the impact of adopting MDT approach in a tertiary HIV clinic in Muscat, Sultanate of Oman. We introduced MDT approach in our HIV centre in January 2016 where existing team members (counsellors, nurses, social workers, pharmacists and doctors) worked together, through care pathways, to support patients as they go through the HIV care continuum from diagnosis to viral suppression. Notes were reviewed for demographics and clinical data. The primary outcome was HIV viral load (VL) suppression (<20, < 200 and < 1000 copies/ml) in measurements by December 2015 and June 2017. In December 2015, 253 patients were in care; 98.4% (249/253) were on antiretroviral therapy (ART). Median age was 41 years and 70% were males. Median baseline CD4 was 204. In June 2017, 294 were in care with similar patient characteristics to those in care in 2015. The majority, 95.9% (282/294), were on ART; 8 of whom started ART within 3 months, hence excluded from the VL analysis. Overall, VL < 200 and < 1000 rates increased from 71.9% and 78.7% in 2015 to 90.5% and 95.6% in 2017, with relative risk (RR) (95% CI) of 1.26 (1.15-1.37) and 1.21 (1.13-1.30), respectively; p value < 0.0001 for both. In a sub-analysis of 214 patients who were in care in 2015 and remained in care in 2017, VL < 200 and < 1000 rates increased from 78.5% and 85% in 2015 to 90.2% and 94.4% in 2016, with RR (95% CI) of 1.15 (1.06 to 1.25) and 1.11 (1.04-1.18), respectively; p values of 0.0010 for both. MDT approach has significantly improved treatment outcome for existing patients and those who have attended our services since the introduction of the MDT model. PMID- 29792339 TI - Pulmonary hypertension in congenital heart disease. AB - Pulmonary hypertension is defined as a mean pulmonary arterial pressure >=25 mmHg. We focus on its relevance in congenital heart disease, reviewing pathophysiology, diagnosis and management. Pulmonary hypertension is a relatively common complication of congenital heart disease, with adult prevalence between 5 and 10%. A multifactorial cause is recognized, relating to the size and nature of cardiac defect as well as environmental and genetic factors. More complex disease is increasingly recognized rather than pure Eisenmenger complex. Remodeling of the pulmonary vascular bed causes increased pulmonary vascular resistance diagnosed by a collection of investigations including echocardiography, exercise testing, cardiac catheterization, MRI and CT scanning. Management employs disease modifying medications which are now used with increasing benefit. PMID- 29792341 TI - Our experience with using a uniform prophylactic protocol in neurosurgery: surgical-site infection did not occur in 272 operations. AB - PURPOSE: Surgical site infection (SSI) is a source of concern in any surgical procedure. Although studies with high numbers of patients are available, most of these studies were performed by different surgeons and the exact anti-SSI protocol is not mentioned or is not homogeneous in all patients. MATERIALS AND METHODS: We present the results of 272 cases where SSI was successfully prevented in our neurosurgical units and in this study we explain our institutional protocol for achieving this positive result. We included all neurosurgical procedures in our two centers that needed an operating room, undertaken between 9 November 2015 and 6 December 2016, retrospectively. Then we compare our results with the existing literature. RESULTS: We performed 272 neurosurgical procedures on 245 patients. 155 patients were male and 90 were female. We re-operated on 24 patients and 3 of them operated on three times in each instance case and others were operated on twice. The patient's ages ranged from 2 to 86years with the mean being 42.39 +/- 19 years. The cranial site of surgery was more common (129 procedures, 47.4%) and overall 118 operations (43.4%) were accompanied with a prosthetic device placement. We performed 96 emergency procedures. The mean hospitalization time was 6.19 +/- 6.77 days. We followed all patients for at least six months. There were no reports of SSI in our neurosurgical units. CONCLUSION: With a fixed protocol of antisepsis, hand protection and prophylactic antibiotics, there were achieved good results. We recommend the current protocol as an effective measure in the control of infection in the neurosurgical ward. However, further studies are needed with more patients and a stronger study design. PMID- 29792342 TI - Misidentification of copperhead and cottonmouth snakes following snakebites. AB - INTRODUCTION: Copperhead (Agkistrodon contortrix) and cottonmouth or water moccasin (Agkistrodon piscivorus) snakes account for the majority of venomous snakebites in the southern United States. Cottonmouth snakes are generally considered to have more potent venom. Copperheads are considered less venomous and there is some controversy as to whether or not bites from copperhead snakes need to be treated with antivenom. Copperhead and juvenile cottonmouth snakes are both brown in color. The purpose of this study was to evaluate the accuracy of identification by the public and healthcare providers between these two species. METHODS: Snakebite victims sometimes bring dead snakes to the hospital or have taken pictures of the snake. When this occurred, ED personnel were asked to take a picture of the snake, and forward the picture to the state poison control center. The identification of the snake by witnesses and/or hospital personnel was compared to the identification by the state herpetologist. RESULTS: During the study period, there were 286 cases of snakebites reported to the state poison control center. Pictures were obtained on 49 of the responsible snakes. All copperhead snakes were identified correctly by callers. However, only 21% of cottonmouth snakes were identified correctly, with 74% of cottonmouth snakes being identified as copperheads. Both public and medical personnel performed poorly on identification of cottonmouth snakes. CONCLUSIONS: Forty percent of the snakes identified as copperheads were actually cottonmouth snakes. Juvenile cottonmouth snakes were often identified as copperhead snakes. PMID- 29792343 TI - Plasma-initiated graft polymerization as an immobilization platform for metal free Russian propolis ethanol extracts designed specifically for biomaterials. AB - The antibacterial and anti-biofilm activities of propolis have been intensively reported. However, the application of this folk remedy as a means to prevent biomedical implant contamination has yet to be completely evaluated. In response to the significant resistant and infectious attributes of biofilms, biomaterials engineered to possess specific chemical and physical properties were immobilized with metal free Russian propolis ethanol extracts (MFRPEE), a known antibacterial agent. The results obtained from this study begin to examine the application of MFRPEE as a novel alternative method for the prevention of medical and biomedical implant infections. When constructed under specific experimental conditions, immobilized biomaterials showed excellent stability when subjected to simulated body fluid and fetal bovine serum. The ability of immobilized biomaterials to specifically target pathogens (both Gram-positive and Gram-negative biofilm forming bacteria), while promoting tissue cell growth, renders these biomaterials as potential candidates for clinical applications. PMID- 29792344 TI - Direct formylation of 2-pyridone core of 3-N-methylcytisine via Duff reaction; synthesis of 9-enyl, 9-ynyl and 9-imino derivatives. AB - The first direct synthesis of 3-N-methyl-9-formylcytisine via electrophylic formylation is described. It is established, that Vilsmeier-Haack and Gatterman variants of this reaction are unsuccessful in the case with 3-substituted (-) cytisine derivatives, but Duff procedure (with hexamethylenetetramine in trifluoroacetic acid) gives a possibility to obtain the target pseudo aromatic aldehyde with the 69% yield. Convenient precursors for [4 + 2]- or [3 + 2] cycloaddition reactions are obtained by means of condensation of synthesized 3-N methyl-9-formylcytisine with acetone, nitromethane and phosphorous ylides with yields from 70 to 87%. Alternative aprroach to alkenyl products and to 9-alkynyl 3-methylcytisine is realized using the Heck and Sonogashira cross-coupling reactions of methyl vinyl ketone, cyclohexenone or trimethylsilylacetylene with 9 bromo-3-methylcytisine (55, 70 and 60% accordingly). It is shown, that interaction of 3-N-methyl-9-formylcytisine with hydroxylamines leads to corresponding nitrone (93%) and oxime (70%). All individual compounds are isolated by column chromatography and completely characterized on the basis of NMR spectroscopy data. PMID- 29792345 TI - Dysembryoplastic neuroepithelial tumours: clinical, radiological, pathological features and outcome. AB - OBJECT: To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015. MATERIALS AND METHODS: Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring). RESULTS: Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002). CONCLUSION: Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3. PMID- 29792346 TI - Synthesis of novel (-)-Camphene-based thiosemicarbazones and evaluation of anti Mycobacterium tuberculosis activity. AB - In this work the aim of study was the synthesis and evaluation of in vitro anti Mycobacterium tuberculosis activity as well as the cytotoxicity in VERO cells of a series of 17 novel thiosemicarbazones derived from the natural monoterpene (-) camphene by REMA and MTT methods. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of M. tuberculosis H37Rv, especially the derivatives 3, 4a-c, 4f, 4i, 4k, 5 and 6a-b. MIC values of 20 tested compounds ranged from 3.9 to > 250 MUg/mL. It was found that when inserting new nitrogenous groups to the (-)-camphene increased the anti-M. tuberculosis activity of some compounds. The SI was calculated for all compounds that showed highly potent anti-M. tuberculosis activity and the best SI values were 21.36, 26.92 and 31.62 (4b, 6a and 6b), and may be considered potential candidates for future antituberculosis drugs. PMID- 29792347 TI - Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared to traditional three-bag regimen in paracetamol overdose. AB - CONTEXT: The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen. METHODS: A medical chart review was conducted in three Danish medical centers from January 2012 through December 2014. Safety and efficacy data were compared for patients who received the traditional infusion protocol in Denmark or the 20-h two-bag IV regimen. RESULTS: Four hundred and ninety-three cases received the two-bag regimen and 274 received the three-bag regimen. The overall incidence of NAARs was 9% with all being mild to moderate in intensity. Fewer subjects in the two bag group (4%) developed NAARs compared to 17% in the three-bag group (p < .001). Overall, 31 patients (4%) developed hepatotoxicity. There was no apparent difference in hepatotoxicity rates between the groups and no deaths or liver transplants. Patients receiving the two-bag regimen had fewer interruptions or delays (5%) compared to the three-bag regimen cohort (12%). Overall, there were very few medication errors reported (1%). CONCLUSIONS: The incidence of NAARs was lower in patients receiving acetylcysteine in a two-bag regimen compared to the traditional Danish three-bag regimen without an apparent reduction in efficacy. PMID- 29792349 TI - Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution. AB - Fluid filtration in the pulmonary microcirculation depends on the hydrostatic and oncotic pressure gradients across the endothelium and the selective permeability of the endothelial barrier. Maintaining normal fluid balance depends both on specific properties of the endothelium and of the perfusing blood. Although some of the essential properties of blood needed to prevent excessive fluid leak have been identified and characterized, our understanding of these remains incomplete. The role of perfusate viscosity in maintaining normal fluid exchange has not previously been examined. We prepared a high-viscosity perfusion solution (HVS) with a relative viscosity of 2.5, i.e., within the range displayed by blood flowing in vessels of different diameters in vivo (1.5-4.0). Perfusion of isolated murine lungs with HVS significantly reduced the rate of edema formation compared with perfusion with a standard solution (SS), which had a lower viscosity similar to plasma (relative viscosity 1.5). HVS did not alter capillary filtration pressure. Increased endothelial shear stress produced by increasing flow rates of SS, to mimic the increased shear stress produced by HVS, did not reduce edema formation. HVS significantly reduced extravasation of Evans blue labeled albumin compared with SS, indicating that it attenuated endothelial leak. These findings demonstrate for the first time that the viscosity of the solution perfusing the pulmonary microcirculation is an important physiological property contributing to the maintenance of normal fluid exchange. This has significant implications for our understanding of fluid homeostasis in the healthy lung, edema formation in disease, and reconditioning of donor organs for transplantation. PMID- 29792350 TI - Management of veins during microvascular decompression for idiopathic trigeminal neuralgia. AB - OBJECT: To summarize our experience in treating veins during microvascular decompression (MVD) procedures for idiopathic trigeminal neuralgia (TN). METHODS: A total of 210 patients who underwent single MVD for idiopathic TN were retrospectively studied. The offending vessels were summarized. The treatment choices for veins during the operation were reviewed. Postoperative long-term outcomes were determined by follow-up. RESULTS: Veins accounted for 26.7% of the total 262 offending vessels. Neurovascular conflicts were caused by veins alone in 23 patients (11.2%), and they were caused by arteries and veins together in 47 patients (22.8%). The offending veins were cut (15.7%) or saved (84.3%) during the operation. Excellent long-term outcomes were acquired in 78.3% of the patients with venous type TN. CONCLUSION: There are no acknowledged principles guiding the treatment of veins during MVD. Our primary treatment principle is to retain veins as often as possible. PMID- 29792348 TI - Cell division cycle 7 kinase is a negative regulator of cell-mediated collagen degradation. AB - Although extensive work has delineated many of the mechanisms of extracellular matrix (ECM) production, far less is known about pathways that regulate ECM degradation. This is particularly true of cellular internalization and degradation of matrix, which play an underappreciated role in ECM metabolism and lung fibrosis. For example, genetic perturbation of this pathway leads to exacerbated fibrosis in experimental animal models. In this work, we present the results of an unbiased screen of Drosophila phagocytes that yielded multiple genes that, when silenced, led to increased collagen uptake. We further describe the function of cell division cycle 7 kinase (CDC7) as a specific suppressor of collagen uptake. We show that the genetic or pharmacological inhibition of CDC7 results in increased expression of the collagen endocytic receptor Endo180. Chromobox 5 (CBX5) is a putative target of CDC7, and genetic silencing of CBX5 also results in increased Endo180 and collagen uptake. Finally, CRISPR-mediated activation of Endo180 expression results in increased collagen uptake, suggesting that CDC7 regulates collagen internalization through increased Endo180 expression. Targeting the regulatory elements of the collagen degradative machinery may be a useful therapeutic approach in diseases of fibrosis or malignancy. PMID- 29792351 TI - Peroxiredoxin 6 Inhibits Osteogenic Differentiation and Bone Formation Through Human Dental Pulp Stem Cells and Induces Delayed Bone Development. AB - AIMS: Peroxiredoxins (PRDXs) are thiol-specific antioxidant enzymes that regulate redox balance that are critical for maintaining the cellular potential for self renewal and stemness. Stem cell-based regenerative medicine is a promising approach in tissue reconstruction. However, to obtain functional cells for use in clinical applications, stem cell technology still requires improvements. RESULTS: In this study, we found that PRDX6 levels were decreased during osteogenic differentiation in human dental pulp stem cells (hDPSCs). hDPSCs stably expressing Myc-PRDX6 (hDPSC/myc-PRDX6) inhibited cell growth in hDPSCs during osteogenic differentiation and impaired osteogenic phenotypes such as alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenic marker genes [ALP and osteocalcin (OCN)]. hDPSC cell lines stably expressing mutant glutathione peroxidase (PRDX6(C47S)) and independent phospholipase A2 (PRDX6(S32A)) were also generated. Each mutant form of PRDX6 abolished the impaired osteogenic phenotypes, the transforming growth factor-beta-mediated Smad2 and p38 pathways, and RUNX2 expression. Furthermore, in vivo experiments revealed that hDPSC/myc-PRDX6 suppressed hDPSC-based bone regeneration in calvarial defect mice, and newborn PRDX6 transgenic mice exhibited delayed bone development and reduced RUNX2 expression. Innovation and Conclusion: These findings illuminate the effects of PRDX6 during osteogenic differentiation of hDPSCs, and also suggest that regulating PRDX6 may improve the clinical utility of stem cell-based regenerative medicine for the treatment of bone diseases. Antioxid. Redox Signal. 00, 000-000. PMID- 29792352 TI - Probing the settlement signals of Amphibalanus amphitrite. AB - To achieve their reproductive potential, barnacles combine tactile exploration of surface structural properties and integration of cellular signals originating from their antennular sensory setae within a developmentally defined, temporally narrow window of settlement opportunity. Behavioural assays with cyprids coupled with biometric analysis of scanning electron microscopy-acquired images in the presence of specific chemical compounds were used to investigate how settlement on a substratum is altered in response to the presence of these compounds. Impeding tactile exploration was shown which altered cellular signalling and/or induced malformation of anatomical features of the antennular sensory setae, which disrupted the settlement behaviour of the model barnacle species Amphibalanus amphitrite. It is concluded that surface exploration by the cyprids relies on mechanical and nociception-related and calcium-mediated signals while a protein kinase C signalling cascade controls the timely metamorphosis of the cyprids to sessile juveniles. PMID- 29792354 TI - Challenges with biomarkers in cancer drug discovery and development. PMID- 29792353 TI - Gastroretentive raft liquid delivery system as a new approach to release extension for carrier-mediated drug. AB - Gabapentin (GBP), an antiepileptic and anti-neuropathic agent, suffers from short half-life (5-7 h), has narrow absorption window, and is absorbed via carrier mediated mechanism resulting in frequent dosing, poor compliance, and poor bioavailability (<60%). Moreover, GBP is a freely water-soluble drug, thus it is considered a challenging candidate to be formulated as extended release dosage form. In this study, raft forming systems were investigated as a potential drug delivery system for prolonging gastric residence time of GBP. A 23 full factorial design was adopted to study the effect of formulation variables (% gellan gum, % GMO, and % LM-pectin 101), on the percent of GBP released at different time intervals (1, 5, and 8 h) as well as the gel strength, and thus was achieved an optimized formula with zero-order release profile suitable for once-daily administration. In vivo assessment was performed in rats to evaluate gastric residence of the gel formed. In addition, the oral bioavailability of GBP relative to commercially available Neurontin(r) immediate release oral solution was also investigated. Significant increase was observed for Cmax, AUC(0-t), and AUC(0-infinity). The increase in relative bioavailability of GBP from the optimized formula was 1.7 folds. PMID- 29792356 TI - Isochromanes from Aspergillus fumigatus, an endophytic fungus from Cordyceps sinensis. AB - Four previously undescribed isochromanes were isolated from the fermentation broth of an endophytic fungus Aspergillus fumigatus, which was obtained from the fruiting body of Cordyceps sinensis. Their structures were elucidated through extensive spectroscopic analyses. One racemic isochromane was further purified by chiral HPLC to yield a pair of enantiomers and their absolute configurations were determined by quantum chemical ECD calculations. These isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-ME-231) and the result showed that compounds 1a and 2 exhibited moderate growth inhibition against MV4-11 cell line. PMID- 29792355 TI - Patient activation among people living with HIV: a cross-sectional comparative analysis with people living with diabetes mellitus. AB - Standardized self-management supports are an integral part of care delivery for many chronic conditions. We used the validated Patient Activation Measure (PAM(r)) to assess level of engagement for self-management from a sample of 165 people living with HIV (PLWH) and 163 people with diabetes. We conducted multivariable logistic regression to assess associations between demographics and PAM(r) scores. PLWH had high levels of activation that were no different from those of people with diabetes (mean score = 67.2, SD = 14.2 versus 65.0, SD = 14.9, p = 0.183). After adjusting for patient characteristics, only being on disability compared to being employed or a student was associated with being less activated (AOR = 0.276, 95%CI = 0.103-0.742). Our findings highlight the potential for the implementation of existing standardized chronic disease self management programs to enhance the care delivery for PLWH, with people on disability as potential target populations. PMID- 29792358 TI - In vitro activities of Ceiba speciosa (A.St.-Hil) Ravenna aqueous stem bark extract. AB - Several species of the genus Ceiba (Malvaceae) are ethnopharmacologically used. Thus, this study aimed to investigate the in vitro beneficial properties of the aqueous stem bark extract of Ceiba speciosa. The extract presented a great amount of phenolic compounds (117.4 +/- 6.2 mg GAE/g). The antioxidant activity was assessed by DPPH (IC50 = 42.87 MUg/mL), ORAC (2351.17 MUmol TE/g) and FRAP (235.94 MUM FeSO4/g) methods. In addition, the extract reduced MCF-7 cell viability as assessed by MTT. However, it prevented mitochondrial membrane depolarization and reduced caspase-9 activity induced by hydrogen peroxide. In conclusion, these findings indicate the extract is an excellent source of natural antioxidants and is able to protect ROS-induced cell death. Therefore, C. speciosa extract may possess beneficial properties for application in pharmaceutical industry as an antioxidant. However, further studies to better elucidate its mechanisms and to isolate its active compounds are required. PMID- 29792357 TI - Synthesis and in vivo anti-ulcer evaluation of some novel piperidine linked dihydropyrimidinone derivatives. AB - Dihydropyrimidinone derivatives containing piperidine moiety were synthesised in a good yield. All the compounds were confirmed by elemental analysis and spectral data. Anti-ulcer activity of novel dihydropyrimidinone-piperidine hybrids (1-18) was evaluated. Among them, four compounds (3, 8, 11 and 15) were found to be most active in 80% ethanol-induced ulcer experimental animal model. All the potent compounds were further evaluated for anti-ulcer activity by different in vivo anti-ulcer models to study the effect of compounds on anti-secretory and cytoprotective activities. All the active compounds inhibited the formation of gastric ulcers and increased the formation of gastric mucin secretion. Compound 15 was found to be the most potent compound of the series as anti-ulcer agent. Additional experimental studies on lead compound 15 will result in a new class of orally active molecule for anti-ulcer activity. PMID- 29792359 TI - Adverse effect analysis of high-intensity focused ultrasound in the treatment of benign uterine diseases. AB - OBJECTIVE: To retrospectively analyze the adverse effects of high-intensity focused ultrasound (HIFU) in management of benign uterine diseases. MATERIALS AND METHODS: From 2011 to 2017, 27,053 patients with benign uterine diseases were treated with HIFU in 19 centers in China. Among them, 17,402 patients had uterine fibroids, 8434 had adenomyosis, 876 had caesarean scar pregnancies, and 341 had placenta accreta. RESULTS: The median age, height, weight, BMI of the patients was 42 years, 158 mm, 56 kg, 22.5 kg/cm2, respectively. After HIFU treatment, 13,170 adverse events were observed. Based on society of interventional radiology classification system, these adverse events were classified as Class A (47.5030%), Class B (0.7947%), Class C (0.3327%), and Class D (0.0518%). The rate of major adverse effects (Class C&D) was 0.3844%. Major adverse effects include skin burn, leg pain, vaginal discharge or bleeding, urinary retention, acute cystitis, intrauterine infection, bowel injury, acute renal failure, deep vein thrombosis, pubic symphysis injury, post-HIFU thrombocytopenia, sciatic nerve injury, and hydronephrosis. In 2011, the annual rate of major adverse effects was 0.9565%; the incidence decreased to 0.2852% in 2017. No significant difference was observed in the rates of major adverse effects between patients with uterine fibroids, adenomyosis and placenta accreta. CONCLUSIONS: Based on the results with low rate of major adverse effects from multiple centers, we concluded that HIFU is safe in treating patients with benign uterine diseases. With development of this technique and more experience on the part of the physicians, the rates of the major adverse effects will be further lowered. PMID- 29792361 TI - Effect of blueberry extract, carriers, and combinations on the growth rate of probiotic and pathogenic bacteria. AB - The blueberry is recognised as a source of phenolic compounds that have beneficial effects on human health; however, they possess low bioavailability and can be degraded by gastrointestinal conditions. Encapsulation has been widely used to mitigate these disadvantages; Gum Arabic (GA) and Corn Syrup Solids (CSS) are common carriers used in this technique. The aim of this study was to evaluate the effect of Blueberry Extract (BE), carriers and their mixtures on the kinetic growth and maximal growth rate of probiotics and pathogenic bacteria. Kinetics were performed in MRS medium with and without a carbon source through Optical Density (OD) measurements and fitting these to the logistic model to compare the maximal growth rates (umax) of the microorganisms. Each food component and its mixtures exert a different influence on the umax of the bacteria studied (p < 0.05). This knowledge is important to improve the design of additives and functional foods. PMID- 29792362 TI - Studies of Suicidal Behavior Using National Registers. PMID- 29792360 TI - Newer human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents. AB - Human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2), being an age-old target, has attracted attention recently for anticancer drug development. Mycophenolic acid (MPA), a well-known immunosuppressant drug, was used a lead structure to design and develop modestly potent and selective analogues. The steep structure-activity relationship (SAR) requirements of the lead molecule left little scope to synthesise newer analogues. Here, newer MPA amides were designed, synthesised and evaluated for hIMPDH2 inhibition and cellular efficacy in breast, prostate and glioblastoma cell lines. Few title compounds exhibited cellular activity profile better than MPA itself. The observed differences in the overall biological profile could be attributed to improved structural and physicochemical properties of the analogues over MPA. This is the first report of the activity of MPA derivatives in glioblastoma, the most aggressive brain cancer. PMID- 29792364 TI - Current evidence in the stability of medicines in dose administration aids: implications for patient safety. AB - INTRODUCTION: As the elderly population and polypharmacy are increasing, it is predicted that interventions to enhance medication adherence, as dose administration aids (DAA), will grow. One of the limitations of repackaging medicines into DAA is to assure the stability of medicines, and, therefore, their quality, efficacy and safety. Area covered: This article collects and summarises data of all the stability studies of repackaged medicines into DAAs. Computerized search in databases: PubMed, Google Scholar, SciELO, and reference texts related to the field (keywords: drug stability, DAAs, compliance aids, and repackaging), open access databases and guidelines. Also, it provides recommendations on the suitability of repackaging and compares them with those established. Expert opinion: Since medicines are removed from primary package, their stability can be compromised due to psychochemical characteristics of the drug substance and product, the dosage form, the type of DAA selected, the co-storage and splitting, the repackaging conditions, and the conditions of storage. This review reflects the need of more standardized stability studies to guarantee the quality of repackaged medicines. In addition, the importance of them to support the pharmacist to make the best decisions in order to maximize outcomes and minimize risks related to patients' medication when repackaging it. PMID- 29792366 TI - Nutritional characterisation of Zambian Moringa oleifera: acceptability and safety of short-term daily supplementation in a group of malnourished girls. AB - In Zambia, chronic malnutrition still is one of the most common problem among children. To fight against malnutrition, the easiest short-term solution could be to combine specific types of food with affordable local plants. A large variety of natural food resources grow in Zambia, such as Moringa oleifera (MO), whose leaves are known for their health benefits, but are not consumed much by local populations. We analysed Zambian MO powder obtained from dried leaves and found that it contains large amounts of protein, minerals and vitamins, such as iron, calcium and carotenoids. These characteristics make MO a good and sustainable complementary solution to malnutrition. We also evaluated the acceptability and the safety of dietary supplementation with MO powder in malnourished children for 30 days. A daily dose of 14 g daily was safe and well accepted. Its regular use in the menu of local populations may be viable proposition. PMID- 29792365 TI - Protective effects of piceatannol on methylglyoxal-induced cytotoxicity in MC3T3 E1 osteoblastic cells. AB - Methylglyoxal (MG) is a reactive alpha-oxoaldehyde that increases under diabetic conditions and subsequently contributes to the complications associated with this disease. Piceatannol is a naturally occurring analogue of resveratrol that possesses multiple biological functions. The present study investigated the effects of piceatannol on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Piceatannol significantly restored MG-induced reductions in cell viability and reduced lactate dehydrogenase release in MG-treated MC3T3-E1 osteoblastic cells, which suggests that it suppressed MG-induced cytotoxicity. Piceatannol also increased glyoxalase I activity and glutathione levels in MG-treated cells, which indicates that it enhanced the glyoxalase system and thus cellular protection. The present study also showed that piceatannol inhibited the generation of inflammatory cytokines and reactive oxygen species and ameliorated mitochondrial dysfunction induced by MG. Furthermore, piceatannol treatment significantly reduced the levels of endoplasmic reticulum stress and autophagy induced by MG. Therefore, piceatannol could be a potent option for the development of antiglycating agents for the treatment of diabetic osteopathy. PMID- 29792368 TI - Electrophysiological Multimodal Assessments Improve Outcome Prediction in Traumatic Cervical Spinal Cord Injury. AB - Outcome prediction after spinal cord injury (SCI) is essential for early counseling and orientation of the rehabilitative intervention. Moreover, prognostication of outcome is crucial to achieving meaningful stratification when conceiving clinical trials. Neurophysiological examinations are commonly employed for prognostication after SCI, but whether neurophysiology could improve the functional prognosis based on clinical predictors remains an open question. Data of 224 patients included in the European Multicenter Study about Spinal Cord Injury were analyzed with bootstrapping analysis and multivariate logistical regression to derive prediction models of complete functional recovery in the chronic stage after traumatic cervical SCI. Within 40 days after SCI, we evaluated age, gender, the motor and sensory cumulative scores of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), and neurophysiological variables (motor evoked potentials, sensory evoked potentials, nerve conduction study) as possible predictors. Positive outcome was defined by a Spinal Cord Independence Measure total score of 100. Analyzing clinical variables, we derived a prediction model based on the ISNCSCI total motor score and age: the area under the receiver operating curve (AUC) was 0.936 (95% confidence interval [CI]: 0.904-0.968). Adding neurophysiological variables to the model, the AUC increased significantly: 0.956 (95% CI: 0.930 0.982; p = 0.019). More patients could be correctly classified by adding the electrophysiological data. Our study demonstrates that neurophysiological assessment improves the prediction of functional prognosis after traumatic cervical SCI, and suggests the use of neurophysiology to optimize patient information, rehabilitation, and discharge planning and the design of future clinical trials. PMID- 29792367 TI - Visual and visuomotor processing of hands and tools as a case study of cross talk between the dorsal and ventral streams. AB - A major principle of organization of the visual system is between a dorsal stream that processes visuomotor information and a ventral stream that supports object recognition. Most research has focused on dissociating processing across these two streams. Here we focus on how the two streams interact. We tested neurologically-intact and impaired participants in an object categorization task over two classes of objects that depend on processing within both streams-hands and tools. We measured how unconscious processing of images from one of these categories (e.g., tools) affects the recognition of images from the other category (i.e., hands). Our findings with neurologically-intact participants demonstrated that processing an image of a hand hampers the subsequent processing of an image of a tool, and vice versa. These results were not present in apraxic patients (N = 3). These findings suggest local and global inhibitory processes working in tandem to co-register information across the two streams. PMID- 29792369 TI - Gene delivery in the cornea: in vitro & ex vivo evaluation of solid lipid nanoparticle-based vectors. AB - AIM: Inflammation is a process that underlies sight-threatening ocular surface diseases, and gene supplementation with the plasmid that encodes for p-IL10 will allow the sustained de novo synthesis of the cytokine to occur in corneal cells, and provide a long-term anti-inflammatory effect. This work describes the development of solid lipid nanoparticle systems for the delivery of p-IL10 to transfect the cornea. RESULTS: In vitro, vectors showed suitable features as nonviral vectors (size, zeta-potential, DNA binding, protection and release), and they were able to enter and transfect human corneal epithelial cells. Ex vivo, the vectors were found to transfect the epithelium, the stroma and the endothelium in rabbit corneal explants. Distribution of gene expression within the cell layers of the cornea depended on the composition of the four vectors evaluated. CONCLUSION: Solid lipid nanoparticle-based vectors are promising gene delivery systems for corneal diseases, including inflammation. PMID- 29792370 TI - Efficacy and safety of intravenous belimumab in Japanese patients with systemic lupus erythematosus: A subgroup analysis of a phase 3 randomized placebo controlled trial. AB - OBJECTIVES: To assess the efficacy and safety of intravenous (IV) belimumab plus standard systemic lupus erythematosus (SLE) therapy standard of care (SoC) in Japanese patients with SLE. METHODS: A Phase 3, multicenter, double-blind, placebo-controlled, 52-week study (BEL 113750; NCT01345253) in patients with SLE, randomized 2:1 to belimumab 10 mg/kg plus SoC or placebo plus SoC to Week 48. RESULTS: Sixty of 707 randomized patients were enrolled from study centers in Japan (belimumab, n = 39; placebo, n = 21). In this cohort, more patients achieved SLE Responder Index 4 response at Week 52 in the belimumab group compared with placebo (46.2% [18/39] vs. 25.0% [5/20]; odds ratio, 2.57 [95% confidence interval: 0.78, 8.47]; p=.1204). Fewer patients receiving belimumab experienced a severe flare through Week 52, with longer median time to flare compared with placebo. More patients with baseline prednisone dose >7.5 mg/d receiving belimumab had a dose reduction of >=25% from baseline to <=7.5 mg/d during Weeks 40-52, compared with placebo. No new safety issues were identified within the Japanese cohort. CONCLUSION: In Japanese patients with SLE, belimumab improved disease activity, with efficacy and safety results similar and consistent to the pivotal Phase 3 trials, suggesting that belimumab is a potential treatment option in this population. PMID- 29792371 TI - Biologics Monitoring: Incongruity between Recommendations and Clinician Monitoring Trends. AB - BACKGROUND: Biologics are a commonly used treatment for moderate to severe psoriasis. Monitoring laboratory test overuse provide little definitive benefit to patients. OBJECTIVE: We aim to query a Humana database to gain insight regarding current dermatologist laboratory monitoring practices for psoriasis patients on biologics. METHODS: Data were obtained from the Humana database. Our cohort included 333 patients with primary ICD-9 diagnosis of psoriasis (696.1) between the years 2008-2013 who are prescribed any biologic medication. Subjects on methotrexate, acitretin or cyclosporine were excluded from the study. We separately queried laboratory tests by CPT codes and quantified based on frequency over a 2-year time period. Percentages of demographic group receiving a laboratory test at a given frequency category were calculated. RESULTS: 46% and 47% of patients received >4 comprehensive metabolic panel and complete blood count tests respectively 2 years after starting a biologic. 18% of individuals age >50 received greater than 4 Basic Metabolic Panel tests respectively 2 years after starting a biologic. LIMITATIONS: Patient comorbidities might confound some of our findings, as these laboratory tests may have been ordered for a comorbidity rather than for biologics side effect monitoring. CONCLUSIONS: There are inconsistencies between current monitoring practices and guidelines. Clarifying biologics monitoring recommendations in psoriasis patients may reduce healthcare costs and provider workload. PMID- 29792372 TI - Sativex(r) as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo controlled randomised clinical trial. AB - : Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex(r)) as add-on therapy to optimised standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity. METHODS: Sativex(r) as add-on therapy vs. further optimised first-line ANTispastics (SAVANT) was a two-phase trial. In Phase A, eligible patients received add-on THC:CBD spray for 4 weeks to identify initial responders [>=20% improvement from baseline in spasticity 0-10 numerical rating scale (NRS) score]. Following washout, eligible initial responders were randomised to receive THC:CBD spray or placebo for 12 weeks (double-blinded, Phase B). Optimisation of underlying antispasticity medications was permitted in both groups across all study periods. RESULTS: Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically relevant responders after 12 weeks (>=30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs. 32.1%; p < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (p < 0.0001), mean pain NRS (p = 0.0013), and mean modified Ashworth's scale (p = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns. CONCLUSIONS: Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first line antispasticity medication alone. PMID- 29792373 TI - Systematic spatial patterns of the sense of familiarity: Hierarchical modelling based on eye-tracking experiments. AB - Using different types of stimuli, such as pictures, horizontally written Japanese words, and vertically written Japanese words, this study investigated the spatial patterns of the sense of familiarity within the visual field. The perceptual asymmetry theory predicted that stimuli in the lower visual field would be processed more fluently and would therefore be perceived as more familiar. The working memory theory, originally proposed in space-number research, envisaged type-specific spatial patterns for different stimuli. Participants made old/new recognition memory judgements for stimuli, presented at random positions, while their eye movements were recorded. The observed spatial patterns changed according to the stimulus type (e.g., "more left = older" for horizontally written words and "upper = older" for vertically written words), and this flexibility is encapsulated by the working memory theory as follows: (a) stimulus type-specific spatial configurations are encoded in long-term memory on the basis of one's experience (e.g., vertically written words are empirically associated with the "upper = older" spatial configuration), (b) the presentation of a stimulus automatically cues the temporal activation of the associated spatial configuration in working memory, and PMID- 29792374 TI - Bimanual control strategies. AB - Two tasks (A and B) were designed which required participants to sequentially move through four target positions in a Lissajous display. Task A was designed so that participants could complete the task using either unimanual or bimanual control strategies. Task B was designed so that participants could complete the task using relatively simple or more complex bimanual control strategies. The purpose of this study was to determine which control strategy the participant utilises to complete the two tasks when Lissajous displays are provided and to determine the degree to which the size of the targets influences the control strategy chosen under these conditions. The movement amplitude between two adjacent targets and the target size resulted in an Index of Difficulty (ID) of 2 and 4 for each task. For both tasks, participants practised 15 trials (30 s per trial) for each ID and then was administered a test trial. The results for both Tasks A and B indicated that the ID2 condition resulted in a circular path, whereas the ID4 condition resulted in a straight-line path on the Lissajous plot. This suggests that at the low ID condition participants produced a continuous 1:1 with 90 degrees phase offset bimanual coordination pattern. At the high ID condition, the participants consistently chose to switch to a more stable unimanual left and right movements in Task A and to transition between in-phase and anti-phase bimanual coordination patterns in Task B. In addition, both limbs' movements were more harmonic in the low ID condition than in the high ID condition. PMID- 29792375 TI - Knowledge and attitudes of family doctors, dermatologists, and endocrinologists on sun exposure and vitamin D. AB - OBJECTIVES: Vitamin D is an important component of bone metabolism. Skin cells synthesize vitamin D when exposed to the sun. However, prolonged sun exposure damages the skin and increases the risk for skin cancer. The objective is to evaluate and compare the attitudes and recommendations of family doctors, dermatologists, and endocrinologists on exposure to the sun and vitamin D. METHODS: In a cross-sectional study, a questionnaire was completed by personal interview in a study population of 78 family doctors, 21 dermatologists, and 22 endocrinologists. RESULTS: On a scale of 1-10, the mean score for recommendations to reduce sun exposure was 4.7 for dermatologists, 4.2 for endocrinologists, and 6.4 for family doctors (p < 0.001). Family doctors recommended a mean daily exposure to the sun of 67.4 min compared to 41.4 by dermatologists, and 47.1 by endocrinologists (p = 0.007). Dermatologists and endocrinologists were more likely to recommend protective measures such as hats and long sleeves during sun exposure than family doctors (p < 0.0001). There were no statistically significant differences between male and female doctors for the entire study population. CONCLUSIONS: There is little consensus among these medical practitioners, whether specialists or primary care doctors, concerning sun exposure. Further studies should evaluate the optimal duration and intensity of sun exposure and doctors' recommendations should be based on the findings. PMID- 29792376 TI - Somatic Angiotensin I-Converting Enzyme Regulates Self-Renewal of Mouse Spermatogonial Stem Cells Through the Mitogen-Activated Protein Kinase Signaling Pathway. AB - Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in the regulation of the renin angiotensin system. In this study, we used reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis to confirm that somatic ACE (sACE), but not testicular ACE (tACE), is expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. sACE was found to play an important role in SSC self-renewal through the regulation of MAPK-dependent cell proliferation. PMID- 29792377 TI - Comparative analysis of probiotic bacteria based on a new definition of core genome. AB - The commensal genus Bifidobacterium has probiotic properties. We prepared a public library of the gene functions of the genus Bifidobacterium for its online annotation. Orthologous gene cluster analysis showed that the pan genomes of Bifidobacterium and Lactobacillus exhibit striking similarities when mapped to the Clusters of Orthologous Group (COG) database of proteins. When the core genes in each genus were selected based on our statistical definition of "core genome", core genes were present in at least 92% of 52 Bifidobacterium and in 97% of 178 Lactobacillus genomes. Functional comparison of the core genes of the two genera revealed a significant difference in the categories "amino acid transport and metabolism" representing their difference in niche specificity. Over-represented Bifidobacterium protein families were primarily involved in host interactions, the complex compound metabolism, and in stress responses. These findings coincide with the published information and validate our bias-resilient definition of the core genome. PMID- 29792378 TI - Location and distribution of craniomaxillofacial fractures in 45 cats presented for the treatment of head trauma. AB - Objectives The aim of this retrospective study was to describe the location and distribution of craniomaxillofacial (CMF) fractures in 45 cats presented to a veterinary referral centre between 2012 and 2017. Methods Cats with a history of head trauma, one or more CMF fractures and a pretreatment CT scan of the CMF region were included in this study. For the purpose of the study, the CMF skeleton was divided into 15 functional anatomical regions and the fracture sites were allocated to one of these functional regions. Statistical analysis was performed using R. Results Skull fractures were evident in 80.0% of cats, and mandibular fractures in 86.7% of cats in this study. The median number of anatomical functional regions affected was eight and there was evidence of moderate or strong correlation between fractures of different regions of the mid face. Where fractures were recorded in the nasopharynx and orbit they were bilateral in 93.5% and 89.7%, respectively. Twenty-six (57.8%) of the cats had fractures affecting one or both temporomandibular joints, which included fractures of the mandibular fossa, condylar neck and condyle. Twenty-nine cats (64.4%) had tooth fractures and seven cats (15.6%) had significant eye injuries. Conclusions and relevance Cats presenting with a single symphyseal separation or parasymphyseal fracture are very likely to have further fractures at other locations. Fractures in the nasopharynx, orbit, nose, upper jaw, inter-maxillary suture and zygomatic arch regions (the 'mid-face') are likely to occur together. The pattern of distribution of mandibular fractures is not as predictable as that for maxillary fractures. CT imaging is required to achieve a complete diagnosis of the location and distribution of skull fractures in cats after head trauma. PMID- 29792379 TI - Role of S-100beta in stroke. AB - The S-100beta levels are associated with a variety of acute disorders and other chronic diseases, such as head injury, stroke, metastatic melanoma, cardiac surgery, bone fractures, burns and contusions. The serum S-100beta levels seem to increase with the volume of tissue damage. Higher serum S-100beta levels have been observed after brain damage or stroke. A number of studies have evidenced the clinical value of S-100beta in the diagnosis and prognosis of stroke while the S-100beta marker is elevated in the peripheral blood during the acute phase of stroke. However, the clinical usefulness of S-100beta biomarker in the diagnosis and prognosis of stroke has a limitation due to its low discriminating ability in stroke diagnosis and prognosis. PMID- 29792381 TI - A photo-switchable and thermal-enhanced fluorescent hydrogel prepared from N isopropylacrylamide with water-soluble spiropyran derivative. AB - Herein, a photo-switchable and thermal-enhanced fluorescent hydrogel has been fabricated from N-isopropylacrylamide (NIPAAm) with a mixture of water-soluble acryloyl-alpha-cyclodextrin/acryloyl-alpha-cyclodextrin-spiropyran (acryloyl alpha-CD/ acryloyl-alpha-CD-SP) as cross-linkers. The physical properties, photochromic properties, and fluorescent behavior of the hydrogel were characterized. The fluorescence emission of the hydrogel can be reversibly switched 'on/off' by UV/visible light irradiation, and meanwhile the fluorescence intensity can be enhanced by increasing the temperature above the volume phase transition temperature (VPTT) of the hydrogel. The hydrogel also shows spatiotemporal fluorescent behavior, excellent cytocompatibility, and fatigue resistance in photochromic and photo-switchable fluorescent behaviors. PMID- 29792382 TI - Ibrutinib-associated ventricular arrhythmia in the FDA Adverse Event Reporting System. PMID- 29792384 TI - Percutaneous leadless pacemaker implantation in a patient with bilateral venous thoracic outlet syndrome. PMID- 29792383 TI - Donor Variation and Optimization of Human Mesenchymal Stem Cell Chondrogenesis in Hyaluronic Acid. AB - Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage repair that can undergo chondrogenesis in a variety of three-dimensional (3D) scaffolds. Hyaluronic acid (HA) hydrogels provide a biologically relevant interface for cell encapsulation. While previous studies have shown that MSC-laden HA constructs can mature in vitro to match native mechanical properties using cells from animal sources, clinical application will depend on the successful translation of these findings to human cells. Though numerous studies have investigated chondrogenesis of human MSC (hMSC)-laden constructs, their functional outcomes were quite inferior to those using animal sources, and donor-specific responses to 3D HA hydrogels have not been fully investigated. To that end, hMSCs were derived from seven donors, and their ability to undergo chondrogenesis in pellet culture and HA hydrogels was evaluated. Given the initial observation of overt cell aggregation and/or gel contraction for some donors, the impact of variation in cell and HA macromer concentration on functional outcomes during chondrogenesis was evaluated using one young/healthy donor. The findings show marked differences in functional chondrogenesis of hMSCs in 3D HA hydrogels based on donor. Increasing cell density resulted in increased mechanical properties, but also promoted construct contraction. Increasing the macromer density generally stabilized construct dimensions and increased extracellular matrix production, but limited the distribution of formed matrix at the center of the construct and reduced mechanical properties. Collectively, these findings suggest that the use of hMSCs may require tuning of cell density and gel mechanics on a donor-by-donor basis to provide for the most robust tissue formation for clinical application. PMID- 29792380 TI - Alirocumab as add-on therapy to statins: current evidence and clinical potential. AB - Atherosclerotic cardiovascular diseases (ASCVDs) are associated with a substantial mortality, physical morbidity, and mental disability. Elevated plasma low-density lipoprotein cholesterol (LDL-C) levels play a major role in the pathophysiology of ASCVDs. Statins have been shown to reduce ASCVD risk and associated events and are recommended as first-line therapy for treatment of hypercholesterolemia by current international guidelines. The key issue is to attain guideline-recommended LDL-C levels (below 70 mg/dl) for patients at very high cardiovascular risk. However, many high-risk and very-high-risk patients on statin therapy remain beyond treatment goals despite lifestyle modification and statins, and are exposed to a high risk of future cardiovascular events including myocardial infarction (MI), stroke, revascularization procedures, and death. This clearly emphasizes the urgent need for additional LDL-C reduction with new therapeutic strategies to target these highly atherogenic particles and to further reduce the burden of ASCVDs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role as a key regulator of the hepatic LDL receptor recycling process. Developments over the past 15 years have demonstrated PCSK9 inhibition to be a novel therapeutic strategy to manage increased LDL-C levels. A number of clinical studies using humanized monoclonal antibody technology against PCSK9 have shown profound reductions of LDL-C levels when used either alone or in combination with statin therapy. Recently, the first cardiovascular outcome study demonstrated a significant reduction of ASCV events when evolocumab was added to a statin therapy. This review will discuss current knowledge about antibody mediated PCSK9 inhibition as add-on therapy to statin and the clinical potential that may be expected. PMID- 29792385 TI - An Organotypic Reconstructed Human Urethra to Study Chlamydia trachomatis Infection. AB - Organotypic models to investigate host-microbiome interactions are still a challenge for the field of tissue engineering. This is particularly the case for organs such as the urethra. Several cell line, animal, and tissue models are available to study Chlamydia trachomatis infections, but none fully reflects natural infection in native human tissue. Therefore, we developed an organotypic reconstructed human urethral model (RhU) to study invasive and noninvasive strains of C. trachomatis. Primary urethra cells were used to reconstruct epithelium on a fibroblast populated collagen-fibrin hydrogel, yielding a RhU. Immunohistochemistry was used to compare RhU with native urethral tissue and to visualize the location of C. trachomatis bacteria in RhU after 10-day exposure. RhU closely resembled native urethral tissue with respect to proliferation and differentiation markers (keratins 6, 10, 13, 17, involucrin, SKALP [skin-derived antileucoproteinase], vimentin, and CD31). Exposure of RhU to noninvasive and invasive C. trachomatis strains revealed relevant differences in infection ability because inclusions were observed (indicating active infection) in the epithelial layer after 10 days exposure only to the invasive strain. The noninvasive strain remained localized on the surface of the epithelial layer. Human primary urethral fibroblasts and keratinocytes can be used to construct RhU that closely resembles native tissue and can be used to investigate active C. trachomatis infections. RhU provides a promising model to investigate host microbiome interactions such as, but not limited to, the human pathogenesis of C. trachomatis. PMID- 29792386 TI - Disparate effects of Shb gene deficiency on disease characteristics in murine models of myeloid, B-cell, and T-cell leukemia. AB - The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma. Wild-type or Shb knockout bone marrow cells expressing the oncogenes were transplanted to bone marrow-deficient recipients. Organs from moribund mice were collected and further analyzed. Shb knockout increased the development of CSF3RT618I-induced leukemia and increased the white blood cell count at the time of death. In the p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase B-cell model, Shb knockout reduced white blood cell counts without affecting latency, whereas in the G12D-Kras T-cell model, thymus size was increased without major effects on latency, suggesting that Shb knockout accelerates the development thymic lymphoma. Cytokine secretion plays a role in the progression of leukemia, and consequently Shb knockout bone marrows exhibited lower expression of granulocyte colony stimulating factor and interleukin 6 in the neutrophilic model and interleukin 7 and chemokine C-X-C motif ligand 12 (C-X C motif chemokine 12) in the B-cell model. It is concluded that in experimental mouse models, the absence of the Shb gene exacerbates the disease in myeloid leukemia, whereas it alters the disease characteristics without affecting latency in B- and T-cell leukemia. The results suggest a role of Shb in modulating the disease characteristics depending on the oncogenic insult operating on hematopoietic cells. These findings help explain the outcome of human disease in relation to Src homology-2 domain protein B mRNA content. PMID- 29792387 TI - Resveratrol prevents high-calorie diet-induced learning and memory dysfunction in juvenile C57BL/6J mice. AB - OBJECTIVE: Because resveratrol (RSV) has been shown to improve learning and memory, so we investigated the potential benefit of RSV on learning and memory deficits in juvenile mice fed with a HC diet and explored the molecular mechanisms underlying this process. METHODS: Six-week-old C57BL/6J mice were divided into three different diet groups: control, HC diet, and HC + RSV diet. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were measured using enzyme-linked immunosorbent assays. Protein expression was examined by immunohistochemistry and western blotting. RESULTS: Administration of RSV daily (30 mg/kg) prevented the HC diet-induced increase in juvenile animal body weight but did not improve any other physiological conditions, including fasting blood glucose and serum cholesterol, triglyceride, insulin, and IGF-1 levels. However, RSV did prevent learning and memory deficits in the HC group. Peroxisome proliferator-activated receptor gamma (PPARgamma) was downregulated in the CA1 region of the hippocampus in both the HC and HC + RSV groups, but the reduction was significantly greater in the HC + RSV group (P < .01 compared with the HC group). Moreover, although the HC diet reduced the number of p16-positive neurons, the HC + RSV diet significantly upregulated p16 expression in the CA1 region of the hippocampus (P < .01 compared with the HC group). CONCLUSIONS: RSV protected against learning and memory impairments in juvenile animals fed with a HC diet, possibly via upregulation of p16 or downregulation of PPARgamma in the hippocampal CA1 region. PMID- 29792389 TI - Therapist-assisted vision therapy improves outcome for stroke patients with homonymous hemianopia alone or combined with oculomotor dysfunction. AB - OBJECTIVE: To improve visual performance and perception in stroke patients suffering from visual impairments by the use of therapist-assisted vision therapy. METHODS: This study was an interventional efficacy open-label investigation. The vision therapy was designed to enhance binocular vision, and saccadic ability, and vergence ranges maximally, and for patients with hemianopia also to improve peripheral awareness. The vision training consisted of one lesson a week for 12 weeks carried out by an optometrist and a vision therapist. Between lessons, patients were to train at home for a minimum of 15-20 min daily. RESULTS: Twenty-four patients completed the course. Significant improvements in visual performance were measured for all test parameters from the baseline to the evaluation after the last lesson of vision training. The COPM results improved both in terms of satisfaction with the completion of a task and with the way the task was carried out (p = 0.001). Groffman tracing test results improved from median 7.5 to 16 (p = 0.002), reading speed in words increased (p = 0.0004), and peripheral awareness of visual markers improved (p = 0.002). CONCLUSION: Therapist-assisted vision therapy increased peripheral visual awareness. Furthermore patients felt safer in the traffic and in outdoor activities. Reading speed significantly increased, and the ability to keep a moving object in focus improved. PMID- 29792388 TI - Cerebral ischaemia/reperfusion injury could be managed by using tramadol. AB - OBJECTIVES: No valid treatment modality that will repair stroke damage and provide neurological recovery has yet been identified in literature. Studies demonstrated that adequate quality of life could be provided if post-stroke pain could be treated sufficiently and timely. Besides its pain relief effects, tramadol has oedema-reducing and anti-inflammatory properties. With these in mind, this study investigated the influence of tramadol in acute and/or chronic ischaemia/reperfusion (I/R) injury. METHODS: Putting aside the Control group, 23 Wistar albino rats were distributed to four groups to investigate the acute (Sham A, TR-A) and chronic (Sham-C, TR-C) periods of I/R injury, and temporary aneurysm clips were applied to their internal carotid arteries for 30 min. Four hours after clippage, tramadol was administered to animals of TR-A and TR-C groups intraperitoneally. After sacrificing all animals, pyknotic and necrotic neuronal cells in hippocampal cornu ammonis (CA)1, CA2, CA3 and parietal cortical regions were counted, and perivascular oedema, intercellular organization disorder (IOD) and inflammatory cell infiltration were scaled histopathologically. Additionally, tissue interleukin (IL)-1beta, IL-10, malondialdehyde, nitric oxide, tumour necrosis factor-alpha, caspase-3, beclin-1, Atg12, LC3II/LC3I levels were measured biochemically. RESULTS: Tramadol could minimize perivascular oedema, IOD, parietal and hippocampal neuronal necrosis, inflammatory cell infiltration in both periods of I/R injury histopathologically. Apart from inhibiting apoptosis and enhancing autophagy, tramadol had no influence on any other biochemical result. DISCUSSION: Tramadol can ameliorate the histopathological structure of ischaemic tissue in both periods of I/R injury in rat. We suggest further research investigating various dosages with different administration methods of tramadol in stroke should be conducted by adopting different explorative techniques. PMID- 29792391 TI - Role of neutrophils in equine asthma. AB - Neutrophilic bronchiolitis is the primary lesion in asthma-affected horses. Neutrophils are key actors in host defense, migrating toward sites of inflammation and infection, where they act as early responder cells toward external insults. However, neutrophils can also mediate tissue damage in various non-infectious inflammatory processes. Within the airways, these cells likely contribute to bronchoconstriction, mucus hypersecretion, and pulmonary remodeling by releasing pro-inflammatory mediators, including the cytokines interleukin (IL) 8 and IL-17, neutrophil elastase, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). The mechanisms that regulate neutrophil functions in the tissues are complex and incompletely understood. Therefore, the inflammatory activity of neutrophils must be regulated with exquisite precision and timing, a task achieved through a complex network of mechanisms that regulates neutrophil survival. The discovery and development of compounds that can help regulate ROS, NET formation, cytokine release, and clearance would be highly beneficial in the design of therapies for this disease in horses. In this review, neutrophil functions during inflammation will be discussed followed by a discussion of their contribution to airway tissue injury in equine asthma. PMID- 29792390 TI - Mental health crisis resolution teams and crisis care systems in England: a national survey. AB - : Aims and methodA national survey investigated the implementation of mental health crisis resolution teams (CRTs) in England. CRTs were mapped and team managers completed an online survey. RESULTS: Ninety-five per cent of mapped CRTs (n = 233) completed the survey. Few CRTs adhered fully to national policy guidelines. CRT implementation and local acute care system contexts varied substantially. Access to CRTs for working-age adults appears to have improved, compared with a similar survey in 2012, despite no evidence of higher staffing levels. Specialist CRTs for children and for older adults with dementia have been implemented in some areas but are uncommon.Clinical implicationsA national mandate and policy guidelines have been insufficient to implement CRTs fully as planned. Programmes to support adherence to the CRT model and CRT service improvement are required. Clearer policy guidance is needed on requirements for crisis care for young people and older adults.Declaration of interestNone. PMID- 29792392 TI - Hemizygous Fabry disease associated with membranous nephropathy: A rare case report?. AB - BACKGROUND: Fabry disease may coexist with various glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis, etc. In this study, we report a rare case of Fabry disease associated with membranous nephropathy (MN). CASE PRESENTATION: A 30-year-old man with nephrotic proteinuria, normal renal function, and no other extrarenal manifestations underwent a renal biopsy in February 2017. Light microscopy and immunofluorescence indicated MN (stage 1). Under an electron microscope, there were subepithelial electron-dense deposits and abundant zebra bodies in podocytes. Both the findings of low-activity alpha galactosidase A (alpha-Gal A, GLA) and base deletion in exon 7 of the GLA gene (GLA-E07.1286_*7 del, a newly reported mutation) confirmed that this patient was simultaneously afflicted with Fabry disease. CONCLUSION: This case report is an important reminder of the role of kidney biopsy, especially electron microscopy, as an indicator of Fabry disease and its rare coexistence with MN.?. PMID- 29792393 TI - Outcomes of transcatheter aortic valve implantation compared with surgical aortic valve replacement in geriatric patients with chronic kidney disease?. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a less invasive treatment modality for patients with severe aortic valve stenosis (AS) who are at a higher risk if they have surgery. Preoperative chronic kidney disease (CKD) influences outcomes of cardiac surgery and is associated with a higher mortality and more complicated hospital course. The aims of our study were to evaluate the comparative outcomes of TAVI versus surgical aortic valve replacement (SAVR) in geriatric patients with preoperative CKD. MATERIALS AND METHODS: We prospectively collected data on patients > 75 years of age who underwent either SAVR or TAVI at Shaare Zedek Medical Center, Jerusalem, Israel. The outcomes studied were postoperative acute kidney injury (AKI), in-hospital and long-term mortality, and major neurologic and infectious morbidity. RESULTS: A total of 318 patients were analyzed, of those, 199 and 119 underwent SAVR and TAVI, respectively. In patients with CKD, there was no statistically significant difference in postoperative AKI. SAVR patients had significantly higher in-hospital mortality (OR 5.9; 95% CI 1.6 - 29.6, p = 0.02), postoperative infection (OR 4.2; 95% CI 1.6 - 12.4, p = 0.005), and longer duration of hospital stay. Mortality at 1 and 2 years was lower in the SAVR group, although the difference was not statistically significant (p = 0.059). CONCLUSION: For elderly patients with CKD who are at a higher risk if they have surgery. TAVI offers a good alternative with lower procedural risk.?. PMID- 29792394 TI - Concomitant administration of candesartan cilexetil in patients on paclitaxel and carboplatin combination therapy increases risk of severe neutropenia?. AB - OBJECTIVE: Angiotensin receptor blockers (ARBs) are often used in patients on paclitaxel (PTX) and carboplatin combination (TC) therapy to treat hypertension caused by the co-administration of bevacizumab. The aim of this retrospective study was to analyze the association between co-administration of ARBs and the development of severe neutropenia in patients on TC therapy. MATERIALS AND METHODS: In this study, 211 concomitant medications were prescribed to 173 patients on TC therapy. 24 of those patients received ARBs. The incidences of neutropenia among those on various ARBs were compared. RESULTS: Patients on candesartan cilexetil had the highest incidence of neutropenia compared to those on other concomitant medications, including other ARBs. Of 173 patients, 6 received candesartan cilexetil during the first cycle of TC therapy, and all 6 of them developed severe neutropenia. We noted that prior to TC therapy, there were no significant differences in age, serum albumin levels, neutrophil counts, liver injury marker, and renal function between the patients on candesartan cilexetil and those on other ARBs. CONCLUSION: Our data suggest that a drug-drug interaction between candesartan cilexetil and TC therapy is probable. Unlike with other ARBs, the possible increased risk for development of severe neutropenia should be taken into account when prescribing candesartan cilexetil in combination with TC therapy.?. PMID- 29792395 TI - How are patients with heart failure treated in primary care??. AB - OBJECTIVE: The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS: Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); beta-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. RESULTS: 178 patients were studied: their mean age was 73.5 years (+/- 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. CONCLUSION: Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.?. PMID- 29792396 TI - Muscle biopsy displaying "double trouble" pathology: Combined features of periodic paralysis and dermatomyositis. PMID- 29792397 TI - A systematic review of the concept and clinical applications of Bone Marrow Aspirate Concentrate in Orthopaedics. AB - INTRODUCTION: Mesenchymal stem cells (MSC's) are believed to have multipotent plasticity with the capability to differentiate along multiple cell lineages such as cartilage, bone, tendon, muscle, and nerve. Such multipotency has the potential to play an important role in the repair and reconstruction of multiple tissues across a number of orthopaedic specialties. Bone marrow and fat are the most abundant and accessible source of MSC's with bone marrow aspirate the most commonly being reported to stimulate healing. METHODS: This review examines the current reported 20 Q2 clinical applications of bone marrow aspirate concentrate and its effectiveness. RESULTS: The published studies reported techniques of collection and preparation of BMAC in addition to its applications in a number of orthopaedic sub-specialities. Studies could be sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (31), reconstruction of osseous defects/non-union (20), treatment of avascular necrosis (9), repair of cartilage defects (8), treatment of sports injuries and tendon injury/repair (9), injection in regenerative therapy (4), treatment of spine conditions (4) including enhancing postoperative fusion and degenerative disc pathology and orthopaedic oncology (4). A few published studies combined the use of platelet-rich plasma (PRP) with BMAC (4) or compared them in different applications (5). CONCLUSIONS: BMAC has been used in bone, cartilage and tendon injuries with encouraging results. PMID- 29792398 TI - Arthroscopic osteochondral autologous transplantation for the treatment of osteochondritis dissecans of the femoral head. AB - Osteochondritis dissecans (OCD) of the femoral head is an unusual cause of hip pain. It can be associated with other intra-articular pathologies including: acetabular labral tears or bone deformities such as Legg-Calve-Perthes Disease (LCPD). In this article, we propose a modern surgical technique using an arthroscopic antegrade and retrograde osteochondral autologous transplantation (OAT) procedure for assessing and treating OCD lesions of the femoral head. PMID- 29792400 TI - Interfering with transmission. AB - The IFNlambda family of interferons controls the spread of viruses in the upper respiratory tract and transmission between mice. PMID- 29792402 TI - Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry. AB - AIMS: The clinical performance of the SYNERGY drug-eluting stent (DES) in patients with acute myocardial infarction (MI) has not been investigated in detail. We sought to report on the outcomes after SYNERGY DES (Boston Scientific, Marlborough, MA, USA) implantation in patients with MI undergoing percutaneous revascularisation (PCI). METHODS AND RESULTS: We included all consecutive patients with MI undergoing PCI with the SYNERGY DES and newer-generation DES (n DES group) in Sweden. From March 2013 to September 2016, a total of 36,292 patients, of whom 39.7% presented with ST-elevation MI, were included. As compared to patients in the n-DES group (n=31,403), patients in the SYNERGY group (n=4,889) were older and presented more often with left main or three-vessel disease involvement, as well as with restenotic lesions (p<0.001 for all parameters). The Kaplan-Meier estimates of ST at two years in the SYNERGY and n DES groups were 0.69% and 0.81%, respectively (adjusted HR 1.00, 95% CI: 0.69 1.46; p=0.99). Clinically relevant restenosis was encountered in 1.48% and 1.25% of patients in the SYNERGY and n-DES groups, respectively (adjusted HR 1.05, 95% CI: 0.81-1.37; p=0.72). No differences in the risk of all-cause death and recurrent MI were found between the two groups after adjustment (adjusted HR 1.12, 95% CI: 0.98-1.28; p=0.10, and adjusted HR 0.95, 95% CI: 0.82-1.10; p=0.49, respectively). CONCLUSIONS: In a large and unselected cohort of patients with MI undergoing percutaneous revascularisation with the SYNERGY DES, stent performance and clinical outcomes did not differ compared with other n-DES up to two years. PMID- 29792399 TI - Meniscal allograft transplantation: a meta-analysis. AB - PURPOSE: This meta-analysis evaluates the mid- to long-term survival outcome of MAT (meniscal allograft transplantation). Potential prognosticators, with particular focus on chondral status and age of the patient at the time of transplantation, were also analysed. STUDY DESIGN: Meta-analysis. METHODS: An online database search was performed using following search string: "meniscal allograft transplantation" and "outcome". A total of 65 articles were analysed for a total of 3157 performed MAT with a mean follow-up of 5.4 years. Subjective and clinical data was analysed. RESULTS: The subjective and objective results of 2977 patients (3157 allografts) were analysed; 70% were male, 30% were female. Thirty-eight percent received an isolated MAT. All other patients underwent at least one concomitant procedure. Lysholm, Knee injury and Osteoarthritis Outcome (KOOS), International Knee Documentation Committee (IKDC) and Visual Analogue Scale (VAS) scores were analysed. All scores showed a good patient satisfaction at long-term follow-up. The mean overall survival rate was 80.9%. Complication rates were comparable to standard meniscal repair surgery. There was a degenerative evolution in osteoarthritis with at least one grade in 1760 radiographically analysed patients. Concomitant procedures seem to have no effect on the outcome. Age at transplantation is a negative prognosticator. The body mass index (BMI) of the patient shows a slightly negative correlation with the outcome of MAT. CONCLUSIONS: MAT is a viable solution for the younger patient with chronic pain in the meniscectomised knee joint. The complications are not severe and comparable to meniscal repair. The overall failure rate at final follow-up is acceptable and the allograft heals well in most cases, but MAT cannot be seen as a definitive solution for post-meniscectomy pain. The correct approach to the chronic painful total meniscectomised knee joint thus requires consideration of all pathologies including alignment, stability, meniscal abnormality and cartilage degeneration. It requires possibly combined but appropriate action in that order. PMID- 29792403 TI - Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study). AB - AIMS: The Oxford Acute Myocardial Infarction PICSO (OxAMI-PICSO) study aimed to assess the efficacy of index of microcirculatory resistance (IMR)-guided therapy with pressure-controlled intermittent coronary sinus occlusion (PICSO) in anterior ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Patients with anterior STEMI treated with primary percutaneous coronary intervention (pPCI) were enrolled. Pre-stenting IMR was measured and PICSO treatment delivered if pre-stenting IMR was >40. No PICSO treatment was considered in patients with a pre-stenting IMR <=40. The control group was derived from a historical cohort of STEMI patients with pre-stenting IMR >40 enrolled in the observational OxAMI study. IMR was measured after completion of pPCI in all patients and within 48 hours in PICSO patients and controls. Cardiac magnetic resonance imaging was performed per protocol for infarct size (IS) assessment within 48 hours after pPCI and at six months. A total of 105 patients were enrolled (25 PICSO, 50 controls with pre-stenting IMR >40, 30 with pre stenting IMR <=40). Compared to controls, patients treated with PICSO had a lower IMR at 24-48 hours (24.8 [18.5-35.9] vs. 45.0 [32.0-51.3], p<0.001) and lower IS at six months (26.0% [20.2-30.0] vs. 33.0% [28.0-37.0], p=0.006). CONCLUSIONS: An IMR-guided treatment with PICSO in anterior STEMI is feasible and may be associated with reduced IS and improved microvascular function. PMID- 29792401 TI - Synthetic single domain antibodies for the conformational trapping of membrane proteins. AB - Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface. A robust binder selection cascade combining ribosome and phage display enabled the generation of conformation selective, high affinity sybodies against an ABC transporter and two previously intractable human SLC transporters, GlyT1 and ENT1. The platform does not require access to animal facilities and builds exclusively on commercially available reagents, thus enabling every lab to rapidly generate binders against challenging membrane proteins. PMID- 29792404 TI - Culotte stenting for coronary bifurcation lesions with 2nd and 3rd generation everolimus-eluting stents: the CELTIC Bifurcation Study. AB - AIMS: The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2 connector SYNERGY. METHODS AND RESULTS: Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES. A total of 170 patients were included. Technical success and final kissing balloon inflation occurred in >96% of cases. Major adverse cardiovascular or cerebrovascular events (MACCE: a composite of death, myocardial infarction [MI], cerebrovascular accident [CVA] and target vessel revascularisation [TVR]) occurred in 5.9% of patients by nine months. The primary endpoint was a composite of death, MI, CVA, target vessel failure (TVF), stent thrombosis and binary angiographic restenosis. At nine months, the primary endpoint occurred in 19% of XIENCE patients and 16% of SYNERGY patients (p=0.003 for non-inferiority for platform performance). CONCLUSIONS: MACCE rates for culotte stenting using contemporary everolimus-eluting DES are low at nine months. The XIENCE and SYNERGY stents demonstrated comparable performance for the primary endpoint. PMID- 29792405 TI - Inhaled Glucocorticoids in Asthma. PMID- 29792406 TI - Inhaled Glucocorticoids in Asthma. PMID- 29792407 TI - Inhaled Glucocorticoids in Asthma. PMID- 29792408 TI - Consequences of the 340B Drug Pricing Program. PMID- 29792409 TI - Consequences of the 340B Drug Pricing Program. PMID- 29792410 TI - [The Standardization Study of Data Communication and Storage for Rehabilitation Devices]. AB - Currently, lacking standards of data communication and storage has been becoming a huge problem in tertiary medical rehabilitation networks. Several rehabilitation management requirements need be met, such as integrating rehabilitation resources, sharing patient data, and augmenting efficiency of rehabilitation therapies. By summarizing existing standards within medical devices and data management, this paper proposed a novel standardized protocol for rehabilitation, which is composed of standards in data format, communication signaling and processing. To demonstrate it, an application in current tertiary medical rehabilitation networks was also proposed in this paper. As a result, the outcomes of this paper are expected to solve the 'information isolated island' problem in current rehabilitation medical rehabilitation networks. PMID- 29792411 TI - [Experiments on the Feature Selection and Classiifcation of Ultrasound Elastography Images for the Diagnosis of Breast Cancers]. AB - Breast cancers are the most common malignant tumors in women, and how to use ultrasound to diagnose breast cancers quantitatively is stil an unsolved problem. This paper extracts five elastic features based on the elastography images of the breast tumors, furthers extract four features related to gray co-occurrence matrix to describe the texture of breast masses. we study the application of SVM classifier to classify these features, and uses the consistency, classification accuracy, ROC curve and AUC (area under the curve) to assess the classification results. we used ultrasound imaging technique to colect data from the actual patients, with the data of 195 lesions in 142 patients. Experimental results show that the classification performance of the elastic features is good, and the support vector machine is suitable for breast image classification, and its classification accuracy is high, which provides a good value for diagnosis. Meanwhile, it is found that the extracted features related to gray level co occurrence matrix have a low diagnostic value. PMID- 29792412 TI - Facet-Dependent Kinetics and Energetics of Hematite for Solar Water Oxidation Reactions. AB - The performance of a photoelectrochemical (PEC) system is highly dependent on the charge separation, transport and transfer characteristics at the photoelectrode|electrolyte interface. Of the factors that influence the charge behaviors, the crystalline facets of the semiconductor in contact with the electrolyte play an important role but has been poorly studied previously. Here, we present a study aimed at understanding how the different facets of hematite affect the charge separation and transfer behaviors in a solar water oxidation reaction. Specifically, hematite crystallites with predominantly {012} and {001} facets exposed were synthesized. Density functional theory (DFT) calculations revealed that hematite {012} surfaces feature higher OH coverage, which was confirmed by X-ray photoelectron spectroscopy (XPS). These surface OH groups act as active sites to mediate water oxidation reactions, which plays a positive role for the PEC system. These surface OH groups also facilitate charge recombination, which compromises the charge separation capabilities of hematite. Indeed, intensity modulated photocurrent spectroscopy (IMPS) confirmed that hematite {012} surfaces exhibit higher rate constants for both charge transfer and recombination. Open circuit potential (OCP) measurements revealed that the hematite {012} surface exhibits a greater degree of Fermi level pinning effect. Our results shed light on how different surface crystal structures may change surface kinetics and energetics. The information is expected to contribute to efforts on optimizing PEC performance for practical solar fuel synthesis. PMID- 29792413 TI - Conductive Metal-Organic Frameworks as Ion-to-Electron Transducers in Potentiometric Sensors. AB - This paper describes an unexplored property of conductive metal-organic frameworks (MOFs) as ion-to-electron transducers in the context of potentiometric detection. Several conductive two-dimensional MOF analogues were drop-cast onto a glassy carbon electrode and then covered with an ion-selective membrane to form a potentiometric sensor. The resulting devices exhibited excellent sensing properties toward anions and cations, characterized by a near-Nernstian response and over 4 orders of magnitude linear range. Impedance and chronopotentiometric measurements revealed the presence of large bulk capacitance (204 +/- 2 MUF) and good potential stability (drift of 11.1 +/- 0.5 MUA/h). Potentiometric water test and contact angle measurements showed that this class of materials exhibited hydrophobicity and inhibited the formation of water layer at the electrode/membrane interface, resulting in a highly stable sensing response with a potential drift as low as 11.1 MUA/h. The property of ion-to-electron transduction of conductive MOFs may form the basis for the development of this class of materials as promising components within ion-selective electrodes. PMID- 29792414 TI - Hybrid Assembly of Different-Sized Supertetrahedral Clusters into a Unique Non Interpenetrated Mn-In-S Open Framework with Large Cavity. AB - Reported here is a unique crystalline semiconductor open-framework material built from the large-sized supertetrahedral T4 and T5 clusters with the Mn-In-S compositions. The hybrid assembly between T4 and T5 clusters by sharing terminal MU2-S2- is for the first time observed among the cluster-based chalcogenide open frameworks. Such three-dimensional structure displays non-interpenetrated diamond type topology with extra-large nonframework volume of 82%. Moreover, ion exchange, CO2 adsorption, as well as photoluminescence properties of the title compound are also investigated. PMID- 29792415 TI - Two-Photon-Active Organotin(IV) Complexes for Antibacterial Function and Superresolution Bacteria Imaging. AB - Antibacterial agents with two-photon absorption are expected to play a significant role in biomedical science. Herein, two novel organotin complexes, HLSn1 and HLSn2, based on coumarin were designed, synthesized, and systematically investigated. It was found that these complexes possessed suitable two-photon active cross sections in the near-infrared region. Moreover, complex HLSn1 could efficiently inhibit the growth of Gram-negative Escherichia coli and Gram positive Bacillus subtilis, especially the latter with a minimum inhibitory concentration (MIC; 90%) of 2 +/- 0.14 MUg mL-1, which is lower than that of Kanamycin (Kana, 8 +/- 0.42 MUg mL-1). Importantly, two-photon imaging and superresolution development of bacterial stain revealed that complex HLSn1 can react with bacterial membranes, producing reactive oxygen species (ROS) and leading to cell death. These outcomes provide promising applications in the superresolution bacteria imaging, diagnostics, and treatment of bacterial infectious. PMID- 29792417 TI - Directional Passive Transport of Microdroplets in Oil-Infused Diverging Channels for Effective Condensate Removal. AB - Condensation widely exists in nature and industry, and its performance heavily relies on the efficiency of condensate removal. Recent advances in micro /nanoscale surface engineering enable condensing droplet removal from solid surfaces without extra energy cost, but it is still challenging to achieve passive transport of microdroplets over long distances along horizontal surfaces. The mobility of these condensate droplets can be enhanced by lubricant oil infusion on flat surfaces and frequent coalescence, which lead to fast growth but random motion of droplets. In this work, we propose a novel design of diverging microchannels with oil-infused surfaces to achieve controllable, long-distance, and directional transport of condensing droplets on horizontal surfaces. This idea is experimentally demonstrated with diverging copper and silicon microchannels with nanoengineered surfaces. Along these hierarchical surface structures, microdroplets condense on the top channel wall and submerge into microchannels owing to the capillary pressure gradient in infusing oil. Confined by the microchannel walls, the submerged droplets deform and maintain the back front curvature difference, which enables the motion of droplets along the channel diverging direction. Subsequent droplet coalescences inside the channel further enhance this directional transport. Moreover, fast-moving deformed droplets transfer their momentum to downstream spherical droplets through the infusing oil. As a result, simultaneous passive transport of multiple droplets (20-400 MUm) is achieved over long distances (beyond 7 mm). On these oil-infused surfaces, satellite microdroplets can further nucleate and grow on an oil-cloaked droplet, demonstrating an enlarged surface area for condensation. Our findings on passive condensate removal offer great opportunities in condensation enhancement, self-cleaning, and other applications requiring directional droplet transport along horizontal surfaces. PMID- 29792416 TI - Phosphotriesterase-Magnetic Nanoparticle Bioconjugates with Improved Enzyme Activity in a Biocatalytic Membrane Reactor. AB - The need to find alternative bioremediation solutions for organophosphate degradation pushed the research to develop technologies based on organophosphate degrading enzymes, such as phosphotriesterase. The use of free phosphotriesterase poses limits in terms of enzyme reuse, stability, and process development. The heterogenization of enzyme on a support and their use in bioreactors implemented by membranes seems a suitable strategy, thanks to the ability of membranes to compartmentalize, to govern mass transfer, and to provide a microenvironment with tuned physicochemical and structural properties. Usually, hydrophilic membranes are used since they easily guarantee the presence of water molecules needed for the enzyme catalytic activity. However, hydrophobic materials exhibit a larger shelf life and are preferred for the construction of filters and masks. Therefore, in this work, hydrophobic polyvinylidene fluoride (PVDF) porous membranes were used to develop biocatalytic membrane reactors (BMR). The phosphotriesterase-like lactonase (PLL) enzyme ( SsoPox triple mutant from S. solfataricus) endowed with thermostable phosphotriesterase activity was used as model biocatalyst. The enzyme was covalently bound directly to the PVDF hydrophobic membrane or it was bound to magnetic nanoparticles and then positioned on the hydrophobic membrane surface by means of an external magnetic field. Investigation of kinetic properties of the two BMRs and the influence of immobilized enzyme amount revealed that the performance of the BMR was mostly dependent on the amount of enzyme and its distribution on the immobilization support. Magnetic nanocomposite mediated immobilization showed a much better performance, with an observed specific activity higher than 90% compared to grafting of the enzyme on the membrane. Even though the present work focused on phosphotriesterase, it can be easily translated to other classes of enzymes and related applications. PMID- 29792418 TI - Self-Assembled PdII6 Molecular Spheroids and Their Proton Conduction Property. AB - A series of molecular spheroids (SP1-SP4) was synthesized using pseudolinear bisimidazole and bisbenzimidazole donors in combination with Pd(NO3)2 acceptor via coordination-driven self-assembly. They were characterized by NMR and mass spectrometry, and the solid-state structures of SP1 and SP3 were confirmed by X ray diffraction. Crystal packing revealed the presence of molecular channels with water molecules in the channels as proton source. All the systems showed proton conductivity across a wide range of temperature and relative humidity. Furthermore, the mode of proton conduction in these molecular spheroids was explored by performing a control experiment using 2,4-dinitrophenol molecule, which indicates that the proton conductivity in the present case increases with increasing surface area of these molecular spheroids. PMID- 29792419 TI - As(III) Removal from Drinking Water by Carbon Nanotube Membranes with Magnetron Sputtered Copper: Performance and Mechanisms. AB - Current approaches for functionalizing carbon nanotubes (CNTs) often utilize harsh chemical conditions, and the resulting harmful wastes can cause various environmental and health concerns. In this study, magnetron sputtering technique is facilely employed to functionalize CNT membranes by depositing Cu onto premade CNT membranes without using any chemical treatment. A comparative evaluation of the substrate polymeric membrane (mixed cellulose ester (MCE)), MCE sputtered with copper (Cu/MCE), the pristine CNT membrane (CNT), and CNT membrane sputtered with Cu (Cu/CNT) shows that Cu/CNT possesses mechanically stable structures and similar membrane permeability as MCE. More importantly, Cu/CNT outperforms other membranes with high As(III) removal efficiency of above 90%, as compared to less than 10% by MCE and CNT, and 75% by Cu/MCE from water. The performance of Cu/CNT membranes for As(III) removal is also investigated as a function of ionic strength, sputtering time, co-existing ions, solution pH, and the reusability. Further characterizations of As speciation in the filtrate and on Cu/CNT reveal that arsenite removal by Cu/CNT possibly began with Cu-catalyzed oxidation of arsenite to arsenate, followed by adsorptive filtration of arsenate by the membrane. Overall, this study demonstrates that magnetron sputtering is a promising greener technology for the productions of metal-CNT composite membranes for environmental applications. PMID- 29792420 TI - Enhanced Thermoelectric Properties of Double-Filled CoSb3 via High-Pressure Regulating. AB - It has been discussed for a long time that synthetic pressure can effectively optimize thermoelectric properties. The beneficial effect of synthesis pressures on thermoelectric properties has been discussed for a long time. In this paper, it is theoretically and experimentally demonstrated that appropriate synthesis pressures can increase the figure of merit (ZT) through optimizing thermal transport and electronic transport properties. Indium and barium atoms double filled CoSb3 samples were prepared use high-pressure and high-temperature technique for half an hour. X-ray diffraction and some structure analysis were used to reveal the relationship between microstructures and thermoelectric properties. In0.15Ba0.35Co4Sb12 samples were synthesized by different pressures; sample synthesized by 3 GPa has the best electrical transport properties, and sample synthesized by 2.5 GPa has the lowest thermal conductivity. The maximum ZT value of sample synthesized by 3.0 GPa reached 1.18. PMID- 29792421 TI - High-Temperature Structural Evolution in the Ba3Mo(1- x)W xNbO8.5 System and Correlation with Ionic Transport Properties. AB - The evolution of the hybrid structure between 9R hexagonal perovskite and palmierite in the entire Ba3Mo(1- x)W xNbO8.5 solid solution (where x = 0, 0.25, 0.5, 0.75, and 1) was probed in the 100-900 K range by synchrotron high resolution powder diffraction. Each sample exhibits a chemical-dependent structural model in the low-temperature regime (from 100 to 500 K) in which 9R and palmierite structures compete each other, the former being progressively favored as tungsten replaces molybdenum. Above 500 K, unit cell parameters and metal site occupancies start to converge toward a similar structural arrangement that is completely reached at 900 K. In fact, at this temperature, the entire solid solution discloses comparable unit cell and an almost enterely occupied M1 site, with a structure that is much closer to palmierite rather than 9R polytype. The present crystallographic results well explain the behavior of the material's bulk ionic conductivity, whose temperature evolution for different compositions depends from the contribution of tetrahedral units proper of the palmierite structure. PMID- 29792422 TI - Toward Total Synthesis of Thiolate-Protected Metal Nanoclusters. AB - Total synthesis, where desired organic- and/or biomolecules could be produced from simple precursors at atomic precision and with known step-by-step reactions, has prompted centuries-lasting bloom of organic chemistry since its conceptualization in 1828 (Wohler synthesis of urea). Such expressive science is also highly desirable in nanoscience, since it represents a decisive step toward atom-by-atom customization of nanomaterials for basic and applied research. Although total synthesis chemistry is less established in nanoscience, recent years have witnessed seminal advances and increasing research efforts devoted into this field. In this Account, we discuss recent progress on introducing and developing total synthesis routes and mechanisms for atomically precise metal nanoclusters (NCs). Due to their molecular-like formula and properties (e.g., HOMO-LUMO transition, strong luminescence and stereochemical activity), atomically precise metal NCs could be regarded as "molecular metals", holding potential applications in various practical sectors such as biomedicine, energy, catalysis, and many others. More importantly, the molecular-like properties of metal NCs are sensitively dictated by their size and composition, suggesting total synthesis of them as an indispensable basis for reliably realizing their practical applications. Atomically precise thiolate-protected Au, Ag and their alloy NCs are employed as model NCs to exemplify design strategies and governing principles in total synthesis of inorganic nanoparticles. This Account starts with a brief summary of total synthesis methodologies of atomically precise metal NCs. Following the methodological summary is a detailed discussion on the mechanisms governing these synthetic strategies, which is the main focus of this Account. Based on unprecedented precision (at atomic resolution) and ease (ensured by size-dependent properties) of tracking clusters' size/structure changes, mechanisms driving growth (e.g., reduction growth and seeded growth) and functionalization (e.g., alloying reaction and ligand exchange) of metal NCs have been explored at molecular level. With definitive step-by-step reaction routes, two-electron (2 e-) reduction (driving the growth reactions) and surface motif exchange (SME, prompting alloying and ligand exchange reactions) are discussed in depth and details. In addition to those sub- and/or individual-cluster level understandings, the self-assembly chemistry delivering high orderliness and enhanced materials performance in NC assemblies/supercrystals is also deciphered. This Account is then concluded with our perspectives toward potential development of cluster chemistry. Advances in total synthesis chemistry of metal NCs could not only serve as guidelines for future synthetic practice of NCs, but also provide molecular-level clues for many pending fundamental puzzles in nanochemistry, including nucleation growth, alloying chemistry, surface engineering and evolution of metamaterials. PMID- 29792423 TI - Trace Organic Pollutant Removal by VUV/UV/chlorine Process: Feasibility Investigation for Drinking Water Treatment on a Mini-Fluidic VUV/UV Photoreaction System and a Pilot Photoreactor. AB - The vacuum-ultraviolet/ultraviolet/chlorine (VUV/UV/chlorine) process, with a VUV/UV mercury lamp used as the light source, was found to be a highly efficient advanced oxidation process (AOP) in a previous study. Hence, its application feasibility for trace organic pollutant removal from drinking water becomes attractive. In this work, a bench-scale mini-fluidic VUV/UV photoreaction system was used to determine the degradation kinetics of sulfamethazine (SMN), a model sulfonamide antibiotic frequently detected with trace levels in aquatic environments. Results indicated that SMN (0.1 mg L-1) could be degraded rapidly by VUV/UV/chlorine, and a synergism was observed between the VUV/UV and UV/chlorine processes. Photon-fluence based rate constants of SMN degradation were determined to be 6.76 * 103 and 8.51 * 103 m2 einstein-1 at chlorine doses of 0.05 and 0.5 mg L-1, respectively. The presence of natural organic matter in real waters significantly inhibited SMN degradation. In addition, pilot tests were conducted to explore the practical performance of the VUV/UV/chlorine process, thereby allowing electrical energy per order to be calculated for cost evaluation. The effect of flow pattern on photoreactor efficiency was also analyzed by computational fluid dynamics simulations. Both bench- and pilot-scale tests have demonstrated that the VUV/UV/chlorine process, as a new AOP, has potential applications to trace organic pollutant removal in small-scale water treatment. PMID- 29792424 TI - Comprehensive Investigation into Luminescent Properties of Ir(III) Complexes: An Integrated Computational Study of Radiative and Nonradiative Decay Processes. AB - A comprehensive and concrete exploration into the deactivation mechanisms of luminescent materials is imperative, with the improvement of simulating and computing technology. In this study, an integrated calculation scheme is employed on five Ir(III) complexes for thorough investigation of their photophysical properties, including radiative ( kr) and nonradiative ( knr) decay rates. As a most famous Ir(III) complex with superior quantum efficiency, fac-Ir(ppy)3 herein serves as a reference relative to the other four beta-diketonate complexes. Both temperature-independent and temperature-dependent knr are taken into account quantitatively for the first time, to unearth the role of different ancillary ligands in the determination of luminescent properties. Since the validated calculations of kr for the five complexes are of the same order of magnitude, the nonemissive peculiarity of 4 is caused by large knr. The newly designed compound 5, which simply has two more -CH2 groups than 4 in the ancillary ligand, further manifests that the reason for large knr in molecule 4 should be attributed to the ligand resonance caused by great pi conjugation. PMID- 29792426 TI - Correction to "Atomic-Scale Influence of Grain Boundaries on Li-Ion Conduction in Solid Electrolytes for All-Solid-State Batteries". PMID- 29792425 TI - Roasted Barley Extract (Mugi-cha) Containing Cyclo(d-Phe-l-Pro) Prevents Lowering of the Cutaneous Blood Flow and Skin Temperature under Air Conditioning: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. AB - Roasted barley extract (RBE), also known as mugi-cha, is a well-known healthy non caffeinated beverage, and its health functionality has been widely reported. Our previous clinical study showed that RBE affects the cutaneous blood flow and skin temperature after cold-water immersion and that cyclo(d-Phe-l-Pro) is responsible for its effect. In this study, we investigated whether cyclo(d-Phe-l-Pro) containing RBE prevents the decrease in the cutaneous blood flow and skin temperature. Subjects remained in the air-conditioned room while ingesting RBE or a placebo. We measured the cutaneous blood flow and skin temperature. We evaluated the effect of RBE administration by two-way repeated measures analysis of variance. A total of 15 subjects were enrolled. The change in cutaneous blood flow in the RBE and placebo groups was -0.79 +/- 0.38 and -2.03 +/- 0.35 mL min-1 100 g-1, respectively ( p value of 0.041). The change in the skin temperature in the RBE and placebo groups was -1.85 +/- 0.35 and -3.02 +/- 0.30 degrees C, respectively ( p value of <0.001). We also did subclass analysis with cold feeling subjects. For the seven subjects who had cold sensation, the change in the cutaneous blood flow in the RBE and placebo groups was -0.48 +/- 0.58 and 2.56 +/- 0.48 mL min-1 100 g-1, respectively ( p value of 0.008). The change in the skin temperature in the RBE and placebo groups was -1.46 +/- 0.74 and -2.89 +/- 0.39 degrees C, respectively ( p value of 0.009). Thus, RBE containing cyclo(d-Phe-l-Pro) prevents the decrease in the cutaneous blood flow and skin temperature under air conditioning. PMID- 29792427 TI - Native Chemical Ligation-Photodesulfurization in Flow. AB - Native chemical ligation (NCL) combined with desulfurization chemistry has revolutionized the way in which large polypeptides and proteins are accessed by chemical synthesis. Herein, we outline the use of flow chemistry for the ligation based assembly of polypeptides. We also describe the development of a novel photodesulfurization transformation that, when coupled with flow NCL, enables efficient access to native polypeptides on time scales up to 2 orders of magnitude faster than current batch NCL-desulfurization methods. The power of the new ligation-photodesulfurization flow platform is showcased through the rapid synthesis of the 36 residue clinically approved HIV entry inhibitor enfuvirtide and the peptide diagnostic agent somatorelin. PMID- 29792428 TI - Structures and Activities of Tiahuramides A-C, Cyclic Depsipeptides from a Tahitian Collection of the Marine Cyanobacterium Lyngbya majuscula. AB - The structures of three new cyclic depsipeptides, tiahuramides A (1), B (2), and C (3), from a French Polynesian collection of the marine cyanobacterium Lyngbya majuscula are described. The planar structures of these compounds were established by a combination of mass spectrometry and 1D and 2D NMR experiments. Absolute configurations of natural and nonproteinogenic amino acids were determined through a combination of acid hydrolysis, derivitization with Marfey's reagent, and HPLC. The absolute configuration of hydroxy acids was confirmed by Mosher's method. The antibacterial activities of tiahuramides against three marine bacteria were evaluated. Compound 3 was the most active compound of the series, with an MIC of 6.7 MUM on one of the three tested bacteria. The three peptides inhibit the first cell division of sea urchin fertilized eggs with IC50 values in the range from 3.9 to 11 MUM. Tiahuramide B (2), the most potent compound, causes cellular alteration characteristics of apoptotic cells, blebbing, DNA condensation, and fragmentation, already at the first egg cleavage. The cytotoxic activity of compounds 1-3 was tested in SH-SY5Y human neuroblastoma cells. Compounds 2 and 3 showed an IC50 of 14 and 6.0 MUM, respectively, whereas compound 1 displayed no toxicity in this cell line at 100 MUM. To determine the type of cell death induced by tiahuramide C (3), SH-SY5Y cells were costained with annexin V-FITC and propidium iodide and analyzed by flow cytometry. The double staining indicated that the cytotoxicity of compound 3 in this cell line is produced by necrosis. PMID- 29792429 TI - Divergent Syntheses of ( Z)-3-Alkylideneisobenzofuran-1(3 H)-ones and 1 H Isochromen-1-ones by Copper-Catalyzed Cycloisomerization of 2-Alkynylbenzoic Acids in Ionic Liquids. AB - The cycloisomerization of readily available 2-alkynylbenzoic acids 1 in ionic liquids (ILs) as recyclable reaction media has been studied under the catalytic action of CuCl2. With substrates bearing an aryl group on the triple bond, a mixture of ( Z)-3-alkylideneisobenzofuran-1(3 H)-ones (from 5- exo- dig cyclization) and 1 H-isochromen-1-ones (from 6- endo- dig cyclization) was observed in 1-ethyl-3-methylimidazolium ethyl sulfate (EmimEtSO4), while the reaction turned out to be selective toward the formation of the isobenzofuranone only using N-ethyl- N-methylmorpholinium dicyanamide [Mor1,2N(CN)2] as the solvent. The 5-membered product was also obtained selectively when the substrate bearing a terminal triple bond was employed, either in EmimEtSO4 or Mor1,2N(CN)2. On the other hand, 2-alkynylbenzoic acids bearing an alkyl or an alkenyl group on the triple bond selectively led, in EmimEtSO4, to 1 H-isochromen-1-ones, while the formation of a regioisomeric mixture was observed in Mor1,2N(CN)2. In any case, the solvent/catalyst system could be easily recycled after extraction of the product from the reaction mixture with diethyl ether. DFT calculations have been carried out to clarify the reaction outcome depending on reaction conditions, and the structures of two representative products, which are ( Z)-3 benzylideneisobenzofuran-1(3 H)-one and ( Z)-3-(4 methylphenylmethylidene)isobenzofuran-1(3 H)-one, have been confirmed by X-ray diffraction analysis. PMID- 29792430 TI - Buchwald-Hartwig Amination of Phosphinines and the Effect of Amine Substituents on Optoelectronic Properties of the Resulting Coupling Products. AB - The Buchwald-Hartwig amination of a phosphinine bearing a bromophenyl moiety was carried out using a dinuclear Ni catalyst. A variety of monoarylamines, diarylamines, and alkylamine, as well as heterocycles, were successfully converted into novel phosphinines bearing amine units. The photophysical properties of these novel phosphinines were examined, including the substituent dependent absorption/emission features and intramolecular charge-transfer interactions. PMID- 29792431 TI - The O + NO( v) Vibrational Relaxation Processes Revisited. AB - We have carried out a quasiclassical trajectory study of the O + NO( v) energy transfer process using DMBE potential energy surfaces for the ground-states of the 2A' and 2A" manifolds. State-to-state vibrational relaxation rate constants have been computed over the temperature range 298 and 3000 K and initial vibrational states between v = 1 and 9. The momentum-Gaussian binning approach has been employed to calculate the probability of the vibrational transitions. A comparison of the calculated state-to-state rate coefficients with the results from experimental studies and previous theoretical calculations shows the relevance of the 1 2A" potential energy surface to the title vibrational relaxation process. PMID- 29792432 TI - New Basis Set for the Evaluation of Specific Rotation in Flexible Biological Molecules in Solution. AB - A detailed theoretical investigation of specific rotation is carried out in solution for nine flexible molecules of biological importance. Systematic search for the main conformers is followed by time-dependent density functional theory (TD-DFT) calculations of specific rotation employing a wide range of basis sets. Due to conformational flexibility of the compounds under study, the possibility of basis set size reduction without deterioration of the results is investigated. The increasing size (d-)aug-cc-pVXZ (X = D, T, Q) bases of Dunning et al., and the ORP basis set, recently developed to efficiently provide molecular specific rotation, are used for this purpose. The polarizable continuum model is employed at all steps of the investigation. Comparison of the present results with the available data obtained in a vacuum reveals considerable differences, the values in solution being much closer to the experimental specific rotation data available. The ORP basis set proves to be competitive with the d-aug-cc-pVDZ set of Dunning in specific rotation calculations carried out in solution. While having the same number of functions, the former yields, in general, results considerably closer to the reference triple-zeta values. We can thus recommend the ORP basis set to study the optical rotation in conformationally flexible molecules in solution. PMID- 29792433 TI - Hinduchelins A-D, Noncytotoxic Catechol Derivatives from Streptoalloteichus hindustanus. AB - Four new catechol derivatives, hinduchelins A-D (1-4), composed of 2,3- dihydroxybenzoic acid, threonine, and decarboxylated phenylalanine, were isolated from Streptoalloteichus hindustanus. Their structures and absolute configurations were elucidated by interpretation of NMR and HRMS data and quantum chemical ECD calculations. The iron-binding properties of the compounds were evaluated by a pyoverdine production assay in Pseudomonas aeruginosa, and compound 4 showed moderate ability to induce pyoverdine production at 50 MUM. None of the compounds were cytotoxic toward HL-20, A549, SMMC-7721, MCF-7, and SW-480 tumor cell lines. PMID- 29792434 TI - Synthesis of Densely Substituted Conjugated Dienes by Transition-Metal-Free Reductive Coupling of Allenylboronic Acids and Tosylhydrazones. AB - Tosylhydrazones and allenylboronic acids underwent a transition-metal-free reductive coupling reaction. This process is suitable for synthesis of tetra- and pentasubstituted conjugated dienes. The corresponding allenyl-Bpin substrate showed a very poor reactivity. The reaction is suggested to involve coupling of the in situ formed diazo compound and allenylboronic acid. The intermediate formed in this coupling undergoes allenyl migration followed by protodeboronation to furnish a conjugated diene as major product. PMID- 29792435 TI - Measuring Drug-Induced Changes in Metabolite Populations of Live Bacteria: Real Time Analysis by Raman Spectroscopy. AB - Raman difference spectroscopy is shown to provide a wealth of molecular detail on changes within bacterial cells caused by infusion of antibiotics or hydrogen peroxide. Escherichia coli strains paired with chloramphenicol, dihydrofolate reductase propargyl-based inhibitors, meropenem, or hydrogen peroxide provide details of the depletion of protein and nucleic acid populations in real time. Additionally, other reproducible Raman features appear and are attributed to changes in cell metabolite populations. An initial candidate for one of the metabolites involves population increases of citrate, an intermediate within the tricarboxyclic acid cycle. This is supported by the observation that a strain of E. coli without the ability to synthesize citrate, gltA, lacks an intense feature in the Raman difference spectrum that has been ascribed to citrate. The methodology for obtaining the Raman data involves infusing the drug into live cells, then washing, freezing, and finally lyophilizing the cells. The freeze dried cells are then examined under a Raman microscope. The difference spectra [cells treated with drug] - [cells without treatment] are time-dependent and can yield population kinetics for intracellular species in vivo. There is a strong resemblance between the Raman difference spectra of E. coli cells treated with meropenem and those treated with hydrogen peroxide. PMID- 29792436 TI - Unveiling the Complex Effects of H2O on Discharge-Recharge Behaviors of Aprotic Lithium-O2 Batteries. AB - The addition of H2O, even trace amount, in aprotic Li-O2 batteries has a remarkable impact on achieving high capacity by triggering solution mechanism, and even reducing charge overpotential. However, the critical role of H2O in promoting solution mechanism still lacks persuasive spectroscopic evidence, moreover, the origin of low polarization remains incompletely understood. Herein, by in situ spectroscopic identification of reaction intermediates, we directly verify that H2O additive is able to alter oxygen reduction reaction (ORR) pathway subjected to solution-mediated growth mechanism of Li2O2. In addition, ingress of H2O also induces to form partial LiOH, resulting in reduced charging polarization due to its higher conductivity; however, LiOH could not contribute to O2 evolution upon recharge. These original results unveil the complex effects of H2O on cycling the aprotic Li-O2 batteries, which are instructive for the mechanism study of aprotic Li-O2 batteries with protic additives or soluble catalysts. PMID- 29792437 TI - Nickel(II)-Catalyzed [8 + 3]-Cycloaddition of 2-Aryl- N-tosylaziridines with Tropone. AB - The Ni-catalyzed [8 + 3]-cycloaddition of tropone with 2-aryl- N-tosylaziridines proceeded smoothly under mild reaction conditions, affording various 4-tosyl 2,3,4,4a-tetrahydrocyclohepta[ b][1,4]oxazine derivatives in moderate to excellent yields. PMID- 29792438 TI - Collimonins A-D, Unstable Polyynes with Antifungal or Pigmentation Activities from the Fungus-Feeding Bacterium Collimonas fungivorans Ter331. AB - The isolation and structure elucidation of collimonins A-D (1-4) from the fungus feeding bacterium Collimonas fungivorans Ter331 are reported. Collimonins are new derivatives of polyoxygenated hexadecanoic acid, including an ene-triyne moiety. Their absolute configurations were fully determined by combining spectroscopic, chemical, and crystalline sponge methods. Collimonins showed antifungal or pigmentation activities against the fungus Aspergillus niger ATCC 9029. PMID- 29792439 TI - The Power of Triplet and Singlet Oxygen in Synthesis: 2-Oxindoles, 3-Hydroxy-2 oxindoles, and Isatins from Furans. AB - A straightforward synthesis of substituted 2-oxindoles, 3-hydroxy-2-oxindoles, and isatins has been developed. Easily accessible furans were transformed into tetrahydropyranopyrrolones by a singlet oxygen initiated cascade reaction sequence. An acid-catalyzed rearrangement, followed by aromatization, gave access to a variety of 2-oxindole motifs, which were oxidized to 3-hydroxy-2-oxindoles or isatins using methylene blue as a radical initiator and molecular oxygen as a terminal oxidant. PMID- 29792440 TI - Looking at the eyes interferes with facial emotion recognition in alexithymia. AB - Alexithymia refers to difficulties in identifying, differentiating, and describing feelings. This personality trait is highly prevalent in many psychiatric conditions and may drive associated social-emotional problems, including the ability to decode emotions in faces. This study probed alexithymic problems with identifying clear and ambiguous blends of emotions in faces and their underlying visual attention patterns. Using the Toronto Alexithymia Scale 20, students with high alexithymia (HA, n = 73) or low alexithymia (LA, n = 76) were enrolled in this study. Participants judged the mixture ratio of emotional expressions while their eye movements were recorded. Controlling for group differences in mood and anxiety, HA showed similar accuracy but a reduced viewing preference of facial eye regions compared to LA (p = .02). More attention to the eye regions was related to lower accuracy in HA (p = .02) but to slightly higher accuracy in LA (p = .07). The current findings point to a role of alexithymia in attentional avoidance of other people's eyes, similar to previous findings in autism spectrum disorder. Eye contact may be perceived as a greater emotional challenge by those with alexithymia, disrupting downstream processing of facial emotions. (PsycINFO Database Record PMID- 29792441 TI - Human memory reconsolidation: A guiding framework and critical review of the evidence. AB - Research in nonhuman animals suggests that reactivation can induce a transient, unstable state in a previously consolidated memory, during which the memory can be disrupted or modified, necessitating a process of restabilization in order to persist. Such findings have sparked a wave of interest into whether this phenomenon, known as reconsolidation, occurs in humans. Translating research from animal models to human experiments and even to clinical interventions is an exciting prospect, but amid this excitement, relatively little work has critically evaluated and synthesized existing research regarding human memory reconsolidation. In this review, we formalize a framework for evaluating and designing studies aiming to demonstrate human memory reconsolidation. We use this framework to shed light on reconsolidation-based research in human procedural memory, aversive and appetitive memory, and declarative memory, covering a diverse selection of the most prominent examples of this research, including studies of memory updating, retrieval-extinction procedures, and pharmacological interventions such as propranolol. Across different types of memory and procedure, there is a wealth of observations consistent with reconsolidation. Moreover, some experimental findings are already being translated into clinically relevant interventions. However, there are a number of inconsistent findings, and the presence of alternative explanations means that we cannot conclusively infer the presence of reconsolidation at the neurobiological level from current evidence. Reconsolidation remains a viable but hotly contested explanation for some observed changes in memory expression in both humans and animals. Developing effective and efficient new reconsolidation-based treatments can be a goal that unites researchers and guides future experiments. (PsycINFO Database Record PMID- 29792442 TI - The case against specialized visual-spatial short-term memory. AB - The dominant paradigm for understanding working memory, or the combination of the perceptual, attentional, and mnemonic processes needed for thinking, subdivides short-term memory (STM) according to whether memoranda are encoded in aural verbal or visual formats. This traditional dissociation has been supported by examples of neuropsychological patients who seem to selectively lack STM for either aural-verbal, visual, or spatial memoranda, and by experimental research using dual-task methods. Though this evidence is the foundation of assumptions of modular STM systems, the case it makes for a specialized visual STM system is surprisingly weak. I identify the key evidence supporting a distinct verbal STM system-patients with apparent selective damage to verbal STM and the resilience of verbal short-term memories to general dual-task interference-and apply these benchmarks to neuropsychological and experimental investigations of visual spatial STM. Contrary to the evidence on verbal STM, patients with apparent visual or spatial STM deficits tend to experience a wide range of additional deficits, making it difficult to conclude that a distinct short-term store was damaged. Consistently with this, a meta-analysis of dual-task visual-spatial STM research shows that robust dual-task costs are consistently observed regardless of the domain or sensory code of the secondary task. Together, this evidence suggests that positing a specialized visual STM system is not necessary. (PsycINFO Database Record PMID- 29792443 TI - Sympathy and responses to suffering: Similarity and variation in China and the United States. AB - Feeling sympathy in response to suffering appears to be a universal human experience, but we know very little about how it is experienced in non-Western cultures. In the present studies, we show that sympathy is a complex emotion that has a distinct appraisal theme of wanting to alleviate suffering and that cultural variation occurs in interpretations of suffering and behavioral responses. In particular, the present studies show that sympathy is conceptualized similarly in both the United States and China (Studies 1 and 2), and that it is elicited by undeserved suffering in both cultures (Study 2), is experienced as unpleasant (Study 2), and motivates a desire to help others (Studies 2, 3, and 4). Results also revealed cultural differences in attributions of suffering, perceptions of deservingness, and behavioral tendencies to help and punish individuals who are suffering. The present findings support sympathy as a distinct emotion that responds to suffering and open the door for cultural variation in interpretations and responses to suffering, including decisions to help. (PsycINFO Database Record PMID- 29792444 TI - Automaticity in the recognition of nonverbal emotional vocalizations. AB - The ability to perceive the emotions of others is crucial for everyday social interactions. Important aspects of visual socioemotional processing, such as the recognition of facial expressions, are known to depend on largely automatic mechanisms. However, whether and how properties of automaticity extend to the auditory domain remains poorly understood. Here we ask if nonverbal auditory emotion recognition is a controlled deliberate or an automatic efficient process, using vocalizations such as laughter, crying, and screams. In a between-subjects design (N = 112), and covering eight emotions (four positive), we determined whether emotion recognition accuracy (a) is improved when participants actively deliberate about their responses (compared with when they respond as fast as possible) and (b) is impaired when they respond under low and high levels of cognitive load (concurrent task involving memorizing sequences of six or eight digits, respectively). Response latencies were also measured. Mixed-effects models revealed that recognition accuracy was high across emotions, and only minimally affected by deliberation and cognitive load; the benefits of deliberation and costs of cognitive load were significant mostly for positive emotions, notably amusement/laughter, and smaller or absent for negative ones; response latencies did not suffer under low or high cognitive load; and high recognition accuracy (approximately 90%) could be reached within 500 ms after the stimulus onset, with performance exceeding chance-level already between 300 and 360 ms. These findings indicate that key features of automaticity, namely fast and efficient/effortless processing, might be a modality-independent component of emotion recognition. (PsycINFO Database Record PMID- 29792445 TI - The Society for Industrial and Organizational Psychology's guidelines for education and training: An executive summary of the 2016/2017 revision. AB - The Society for Industrial and Organizational Psychology (SIOP, Division 14 of the American Psychological Association [APA]) maintains Guidelines for Education and Training to provide guidance for the training of industrial-organizational (I O) psychologists. The 2016/2017 revision combines separate documents for master's and doctoral-level training into one document, because the competencies required for each degree are not very different. Instead, the degrees differ in breadth and depth. The updated Guidelines were approved as APA policy in August 2017. In this article, we briefly review the revision process and highlight the updates made in the latest version of the Guidelines. (PsycINFO Database Record PMID- 29792446 TI - An expanded theory of Alzheimer's caregiving. AB - The ancient and cross-culturally prevalent pattern of caregiving suggests that long-term caregiving is species characteristic for humans. If so, then an evolutionary account of the adaptation(s) that underwrite this caregiving is necessary, particularly for the one-sided and long-term nature of Alzheimer's caregiving. Four standard evolutionary explanations are evaluated: kin selection theory, the grandmother hypothesis, direct reciprocity, and indirect reciprocity. Each is found inadequate to explain caregiving because of the lack of reproductive benefits. These evolutionary accounts also assume that relationships are only valuable to the degree that they provide benefits and that relationship partners are predominantly motivated by self-interest. Attachment provides another explanation, which evolved initially to ensure infant protection and nurturance, but was exapted for important adult relationships. Attachment relationships naturally include caregiving and engender long-term relational commitment. Yet attachment theory is ambiguous about whether relationships are maintained for the sake of security benefits or because they have inherent value. This ambiguity undermines the explanatory value of attachment theory for Alzheimer's caregiving. Therefore, a shared identity theory is offered that highlights the inherent value of the relationship and the loved one, transcending the predominant focus on beneficial individual outcomes. The theory emphasizes the frequent human motivation to benefit others because of their mutual commitment, shared identity, and shared goals. The conclusion is that fully understanding and supporting the arduous efforts of caregiving for loved ones with Alzheimer's requires psychologists to fully appreciate and support the deep and meaningful motivations that often inspire the humanity seen in caregiving. (PsycINFO Database Record PMID- 29792447 TI - The source model of group threat: Responding to internal and external threats. AB - We introduce a model of group threat that articulates the opposing effects of intergroup (between-groups) and intragroup (within-group) threat on identity processes and group relations. The source model of group threat argues that the perceived source of a threat is critical in predicting its consequences, such that perceptions of intergroup threat will strengthen (in)group identity processes and relations, whereas perceptions of intragroup threat has the potential to undermine the same. In addition to reviewing the large literature on intergroup threat and a smaller body of unsynthesized work on intragroup threat, we discuss how these processes are captured in representations of monsters (aliens, vampires, and zombies) in popular media and how these ideas can inform interpretation of current political debates, such as those around homegrown terrorism. This model provides a novel summary of the core effects of intergroup and intragroup threat, generating testable hypotheses about the psychological effects of different types of threat. Applying this model will help to make sense of seemingly contradictory findings in the literature, illustrating how appraisal of a threat as originating from an intergroup or intragroup source has the capacity to change the group-based effects of that threat. (PsycINFO Database Record PMID- 29792448 TI - The experimental evidence for parapsychological phenomena: A review. AB - This article presents a comprehensive integration of current experimental evidence and theories about so-called parapsychological (psi) phenomena. Throughout history, people have reported events that seem to violate the common sense view of space and time. Some psychologists have been at the forefront of investigating these phenomena with sophisticated research protocols and theory, while others have devoted much of their careers to criticizing the field. Both stances can be explained by psychologists' expertise on relevant processes such as perception, memory, belief, and conscious and nonconscious processes. This article clarifies the domain of psi, summarizes recent theories from physics and psychology that present psi phenomena as at least plausible, and then provides an overview of recent/updated meta-analyses. The evidence provides cumulative support for the reality of psi, which cannot be readily explained away by the quality of the studies, fraud, selective reporting, experimental or analytical incompetence, or other frequent criticisms. The evidence for psi is comparable to that for established phenomena in psychology and other disciplines, although there is no consensual understanding of them. The article concludes with recommendations for further progress in the field including the use of project and data repositories, conducting multidisciplinary studies with enough power, developing further nonconscious measures of psi and falsifiable theories, analyzing the characteristics of successful sessions and participants, improving the ecological validity of studies, testing how to increase effect sizes, recruiting more researchers at least open to the possibility of psi, and situating psi phenomena within larger domains such as the study of consciousness. (PsycINFO Database Record PMID- 29792449 TI - The science of teamwork: Introduction to the special issue. AB - Provides an introduction to this special issue which explores the Science of Teamwork-what psychological science in 2018 tells us about the process and outcomes of teamwork in a variety of contexts. This work draws from and affects all areas of psychology. The science and practice of teamwork is now an interdisciplinary activity. Teamwork is a complex phenomenon requiring multiple lenses and approaches. What follows is a description of our process in putting together the issue and a brief description of the articles that compose it. (PsycINFO Database Record PMID- 29792450 TI - The evolution of work team research since Hawthorne. AB - Since the Hawthorne studies of the 1920s and 1930s, there has been tremendous progress in the science and the practice of work group effectiveness. We chronicle the evolution of 3 schools of thought concerning work groups that spawned about the time of those studies. We highlight the different emphases of each perspective and how they eventually merged into an integrated view of teamwork. We also illustrate the disciplinary ebbs and flows of work group research over the past quarter century and how many different scholars from diverse institutions are currently contributing to the literature. We highlight the progress that has been made both in terms of scholarly insights and practical advances. We argue that the popular Input-Process-Outcome framework has facilitated progress in the field but has also become a limiting factor. We conclude that future advances will be associated with: (a) the advent of new theories, methodologies, and tools for modeling dynamic team properties; (b) a greater appreciation for, and sophisticated conceptions of, team task environments; and (c) conceptions of teams as entities in multilevel environments. (PsycINFO Database Record PMID- 29792451 TI - The science of teams in the military: Contributions from over 60 years of research. AB - Teams are the foundational building blocks of the military, which uses a hierarchical structure built on and around teams to form larger units. Consequently, team effectiveness has been a substantial focus of research within the military for decades to ensure military teams have the human capabilities to complete their missions and address future challenges successfully. This research has contributed greatly to broader team theory and informed the development of evidence-based interventions. Team-focused research supported or executed by the military has yielded major insights into the nature of team performance, advanced the methods for measuring and improving team performance, and broken new ground in understanding the assembly of effective teams. Furthermore, military research has made major contributions to advancing methodological and statistical techniques for studying teams. We highlight the military contributions to the broader team literature and conclude with a discussion of critical areas of future research on teams and enduring challenges for both the military and team science as a whole. (PsycINFO Database Record PMID- 29792452 TI - Foundations of teamwork and collaboration. AB - The term teamwork has graced countless motivational posters and office walls. However, although teamwork is often easy to observe, it is somewhat more difficult to describe and yet more difficult to produce. At a broad level, teamwork is the process through which team members collaborate to achieve task goals. Teamwork refers to the activities through which team inputs translate into team outputs such as team effectiveness and satisfaction. In this article, we describe foundational research underlying current research on teamwork. We examine the evolution of team process models and outline primary teamwork dimensions. We discuss selection, training, and design approaches to enhancing teamwork, and note current applications of teamwork research in real-world settings. (PsycINFO Database Record PMID- 29792453 TI - Team composition and the ABCs of teamwork. AB - In teams, some combinations of people work together better than others. A large body of literature with a rich history suggests that the configuration of team member attributes, called team composition, has a fundamental influence on teamwork. Team composition shapes the emergence of affective states, behavioral processes, and cognitive states (the ABCs of teamwork), which ultimately affect how teams meet their objectives. The purpose of this article is to describe what is known about team composition and its influence on the ABCs of teamwork. We discuss what team composition is, and why it is important. We then describe key discoveries related to how team composition shapes the ABCs of teamwork. Building on what we know, we outline important directions for future research. (PsycINFO Database Record PMID- 29792454 TI - Addressing the paradox of the team innovation process: A review and practical considerations. AB - Facilitating team innovation is paramount to promoting progress in the science, technology, engineering, and math fields, as well as advancing national health, safety, prosperity, and welfare. However, innovation teams face a unique set of challenges due to the novelty and uncertainty that is core to the definition of innovation, as well as the paradoxical nature of idea generation and idea implementation processes. These and other challenges must be overcome for innovation teams to realize their full potential for producing change. The purpose of this review is, thus, to provide insight into the unique context that these teams function within and provide an integrative, evidence-based, and practically useful, organizing heuristic that focuses on the most important considerations for facilitating team innovation. Finally, we provide practical guidance for psychologists, organizations, practitioners, scientists, educators, policymakers, and others who employ teams to produce novel, innovative solutions to today's problems. (PsycINFO Database Record PMID- 29792455 TI - Debunking key assumptions about teams: The role of culture. AB - Scholars have argued that if psychologists are to gain a true understanding of human behavior, culture should be central to research and theory. The research on teams is an area where better integration between the mainstream and cross cultural literatures is critically needed, given the increasing prevalence of multicultural teams. The purpose of this article is therefore to demonstrate how research focused on culture's influence on teams advances current mainstream theoretical understanding of team effectiveness. Guided by widely accepted frameworks of team effectiveness (Ilgen, Hollenbeck, Johnson, & Jundt, 2005) and culture (Giorgi, Lockwood, & Glynn, 2015), we extract several key assumptions from the mainstream literature that have also been examined within the cross cultural literature. Through a process of comparing and contrasting, we determined which components of current models are upheld and debunked when seeking to generalize these models to other cultural contexts outside of North America. Although we found some consistent results across the two literatures, most of our analyses reveal there are important boundary conditions surrounding common team effectiveness assumptions when culture is considered. By anchoring our analyses around fundamental aspects of teams, including how they form, function, and finish, we then revised these assumptions according to the integration of the teams and cross-cultural literatures. Taken together, we provide a rich foundation for future research, and facilitate a more nuanced understanding of human behavior within the team context. (PsycINFO Database Record PMID- 29792456 TI - Teamwork situated in multiteam systems: Key lessons learned and future opportunities. AB - Many important contexts requiring teamwork, including health care, space exploration, national defense, and scientific discovery, present important challenges that cannot be addressed by a single team working independently. Instead, the complex goals these contexts present often require effectively coordinated efforts of multiple specialized teams working together as a multiteam system (MTS). For almost 2 decades, researchers have endeavored to understand the novelties and nuances for teamwork and collaboration that ensue when teams operate together as "component teams" in these interdependent systems. In this special issue on the settings of teamwork, we aim to synthesize what is known thus far regarding teamwork situated in MTS contexts and offer new directions and considerations for developing, maintaining, and sustaining effective collaboration in MTSs. Our review of extant research on MTSs reveals 7 key lessons learned regarding teamwork situated in MTSs, but also reveals that much is left to learn about the science and practice of ensuring effective multiteam functioning. We elaborate these lessons and delineate 4 major opportunities for advancing the science of MTSs as a critical embedding context for collaboration and teamwork, now and in the future. (PsycINFO Database Record PMID- 29792457 TI - Evaluating problem-solving teams in K-12 schools: Do they work? AB - Teams and other collaborative structures have become commonplace in American schools, although historically school staff members functioned more independently from one another. In this article, we describe the growing influence of collaboration and teaming in a variety of school contexts, but focus on the empirical literature on problem-solving teams as reflecting the state of research and practice in the schools. A review of the research on problem-solving teams, using an input-mediator-outcome-input framework, provides evidence for how teaming could become more effective and efficient in this context as well as sets an agenda for what additional research is needed. Key challenges to school teams are considered next, along with recommendations for change. The first challenge is the lack of training of school staff in the key components of teaming. A second issue is the difficulty in implementing teams in the organizational context of schools. (PsycINFO Database Record PMID- 29792458 TI - The trade-offs of teamwork among STEM doctoral graduates. AB - Teamwork has increasingly become prevalent in professional fields such as academic science, perhaps partly because research shows that teams tend to produce superior work. Although research on teamwork has typically focused on its impact on work products, we complement that work by examining the degree to which teamwork influences salary, hours worked, and overall job satisfaction. Drawing on microdata collected through the National Science Foundation's Survey of Doctorate Recipients as well as the Survey of Earned Doctorates, we find that doctoral degree holders in science, technology, engineering, and mathematics (STEM) fields tend to earn substantially higher salaries and work more hours when they engage in teamwork. We also find no comparable difference in overall job satisfaction as a function of whether individuals work within teams. Additionally, we find evidence that age interacts significantly with teamwork, whereby older teamworkers tend to earn relatively more when participating in teams without appearing to work more hours; and we show that employment sector is important, whereby teamwork is relevant for salaries and hours worked in education and industry but not in government. Although our study is based on market outcomes and behavioral measures, our findings provide grounds for future research that examines the psychological mechanisms that are relevant to understanding why people join teams as well as the psychological consequences that people encounter through teamwork. More generally, this study provides a model for considering individual-level antecedents and outcomes associated with teamwork when degrees of discretion exist with respect to teaming. (PsycINFO Database Record PMID- 29792459 TI - Teamwork in healthcare: Key discoveries enabling safer, high-quality care. AB - Few industries match the scale of health care. In the United States alone, an estimated 85% of the population has at least 1 health care encounter annually and at least one quarter of these people experience 4 to 9 encounters annually. A single visit requires collaboration among a multidisciplinary group of clinicians, administrative staff, patients, and their loved ones. Multiple visits often occur across different clinicians working in different organizations. Ineffective care coordination and the underlying suboptimal teamwork processes are a public health issue. Health care delivery systems exemplify complex organizations operating under high stakes in dynamic policy and regulatory environments. The coordination and delivery of safe, high-quality care demands reliable teamwork and collaboration within, as well as across, organizational, disciplinary, technical, and cultural boundaries. In this review, we synthesize the evidence examining teams and teamwork in health care delivery settings in order to characterize the current state of the science and to highlight gaps in which studies can further illuminate our evidence-based understanding of teamwork and collaboration. Specifically, we highlight evidence concerning (a) the relationship between teamwork and multilevel outcomes, (b) effective teamwork behaviors, (c) competencies (i.e., knowledge, skills, and attitudes) underlying effective teamwork in the health professions, (d) teamwork interventions, (e) team performance measurement strategies, and (f) the critical role context plays in shaping teamwork and collaboration in practice. We also distill potential avenues for future research and highlight opportunities to understand the translation, dissemination, and implementation of evidence-based teamwork principles into practice. (PsycINFO Database Record PMID- 29792460 TI - The complexity, diversity, and science of primary care teams. AB - This article examines the past, present and future of primary care and teamwork. It begins with a definition and description of primary care-its uniqueness, diversity and complexity, including the historical role of teams within primary care. The article then reviews the emergence of innovative primary care teams, including those grounded in new processes such as the Patient-Centered Medical Home and interprofessional teams that include new types of health professionals, particularly psychologists and other integrated behavioral health clinicians. The article describes key factors that support or hinder primary care teamwork, as well as evidence of the impact of these team-based models on patient outcomes, costs, and team members. It also discusses the role of primary care teams within multiteam systems (or 'teams of teams'), which are organized around the needs of patients and families, and the unique challenges these systems pose to coordinating care. The article concludes with recommendations for advancing teams in primary care, including changes in payment, descriptions of team competencies, models for primary care team training, and research necessary to inform the gaps in scientific knowledge. (PsycINFO Database Record PMID- 29792461 TI - Teamwork in the intensive care unit. AB - Intensive care units (ICUs) provide care to the most severely ill hospitalized patients. Although ICUs increasingly rely on interprofessional teams to provide critical care, little about actual teamwork in this context is well understood. The ICU team is typically comprised of physicians or intensivists, clinical pharmacists, respiratory therapists, dieticians, bedside nurses, clinical psychologists, and clinicians-in-training. ICU teams are distinguished from other health care teams in that they are low in temporal stability, which can impede important team dynamics. Furthermore, ICU teams must work in physically and emotionally challenging environments. Our review of the literature reveals the importance of information sharing and decision-making processes, and identifies potential barriers to successful team performance, including the lack of effective conflict management and the presence of multiple and sometimes conflicting goals. Key knowledge gaps about ICU teams include the need for more actionable data linking ICU team structure to team functioning and patient-, family-, ICU-, and hospital-level outcomes. In particular, research is needed to better delineate and define the ICU team, identify additional psychosocial phenomena that impact ICU team performance, and address varying and often competing indicators of ICU team effectiveness as a multivariate and multilevel problem that requires better understanding of the independent effects and interdependencies between nested elements (i.e., hospitals, ICUs, and ICU teams). Ultimately, efforts to advance team-based care are essential for improving ICU performance, but more work is needed to develop actionable interventions that ensure that critically ill patients receive the best care possible. (PsycINFO Database Record PMID- 29792462 TI - Extreme teams: Toward a greater understanding of multiagency teamwork during major emergencies and disasters. AB - Major emergencies are extreme team decision making environments. They are complex, dynamic, high-stakes and fast paced events, wherein successful resolution is contingent upon effective teamwork. Not only do emergency teams coordinate at the intrateam level (e.g., police team), but they are increasingly required to operate at the interteam level (e.g., police, fire and ambulance teams). This is in response to the desire for networked and cost-effective practice and due to the evolving nature of modern threats, such as extreme weather events and terrorist attacks, which require a multi- rather than single agency response. Yet the capacity for interoperability between emergency teams is under researched and poorly understood. Much of the teamwork research is based on student-samples or in artificial lab settings, reducing the salient contextual demands of emergencies (e.g., high-stakes, meaningful risk). Furthermore, the minimal research that has been conducted has tended to provide broad descriptive accounts of challenges faced during emergencies, but failed to develop and test solutions. This article identifies what is known about emergency teams and highlights why it is an important and timely area for research. It will focus on the challenges and solutions to three areas of team processing: cooperation, coordination, and communication. Future research must have a solutions-focused approach. This can be oriented around areas: training, sociotechnical networks, and policies/procedural guidelines. Greater collaboration between academics and practitioners can grow knowledge in this domain, ensuring that interventions to improve emergency teamwork are both contextually grounded and empirically validated. (PsycINFO Database Record PMID- 29792463 TI - Terrorist teams as loosely coupled systems. AB - Acts of terrorism can be harrowing and cause extensive damage, yet they occur far too frequently. How do terrorist groups organize and coordinate their attacks? What makes those groups simultaneously cohesive and flexible in a hostile environment? Different academic disciplines have contributed to a better understanding of the proliferation of terrorist acts in recent years. With very few exceptions, however, extant psychological research on terrorism has almost exclusively focused on the individual terrorist. We leverage the team literature to better understand how a team of terrorists radicalizes, organizes, and makes decisions. Drawing from the work of Weick (1976), we characterize terrorist teams as loosely coupled systems. Examples of different terrorist attacks from the last 15 years illustrate how loose coupling in terrorist teams is especially powerful because of the high familiarity and intimacy among members of terrorist teams. Loosely coupled structures have led to highly adaptive and resilient teams whose actions are fluid, unpredictable, and often lethal. We conclude by discussing implications for counterterrorism and for future research. (PsycINFO Database Record PMID- 29792464 TI - Debriefs: Teams learning from doing in context. AB - Debriefs are a type of work meeting in which teams discuss, interpret, and learn from recent events during which they collaborated. In a variety of forms, debriefs are found across a wide range of organizational types and settings. Well conducted debriefs can improve team effectiveness by 25% across a variety of organizations and settings. For example, the U.S. military adopted debriefs decades ago to promote learning and performance across the various services. Subsequently, debriefs have been introduced in the medical field, the fire service, aviation, education, and in a variety of organizational training and simulation environments. After a discussion of various purposes for which debriefs have been used, we proceed with a historical review of development of the concepts and use in industries and contexts. We then review the psychological factors relevant to debrief effectiveness and the outcomes for individuals, teams, and organizations that deploy debriefs. Future directions of particular interest to team researchers across a variety of psychological disciplines are presented along with a review of how best to implement debriefs from a practical perspective. (PsycINFO Database Record PMID- 29792465 TI - Team development interventions: Evidence-based approaches for improving teamwork. AB - The rate of teamwork and collaboration within the workforce has burgeoned over the years, and the use of teams is projected to continue increasing. With the rise of teamwork comes the need for interventions designed to enhance teamwork effectiveness. Successful teams produce desired outcomes; however, it is critical that team members demonstrate effective processes to achieve these outcomes. Team development interventions (TDIs) increase effective team competencies and processes, thereby leading to improvements in proximal and distal outcomes. The effectiveness of TDIs is evident across domains (e.g., education, health care, military, aviation), and they are applicable in a wide range of settings. To stimulate the adoption and effective use of TDIs, the current article provides a review of four types of evidence-based TDIs including team training, leadership training, team building, and team debriefing. In doing so, we aim to provide psychologists with an understanding of the scientific principles underlying TDIs and their impact on team dynamics. Moreover, we provide evidence-based recommendations regarding how to increase the effectiveness of TDIs as well as a discussion on future research needed within this domain. (PsycINFO Database Record PMID- 29792466 TI - The science of team science: A review of the empirical evidence and research gaps on collaboration in science. AB - Collaborations among researchers and across disciplinary, organizational, and cultural boundaries are vital to address increasingly complex challenges and opportunities in science and society. In addition, unprecedented technological advances create new opportunities to capitalize on a broader range of expertise and information in scientific collaborations. Yet rapid increases in the demand for scientific collaborations have outpaced changes in the factors needed to support teams in science, such as institutional structures and policies, scientific culture, and funding opportunities. The Science of Team Science (SciTS) field arose with the goal of empirically addressing questions from funding agencies, administrators, and scientists regarding the value of team science (TS) and strategies for successfully leading, engaging in, facilitating, and supporting science teams. Closely related fields have rich histories studying teams, groups, organizations, and management and have built a body of evidence for effective teaming in contexts such as industry and the military. Yet few studies had focused on science teams. Unique contextual factors within the scientific enterprise create an imperative to study these teams in context, and provide opportunities to advance understanding of other complex forms of collaboration. This review summarizes the empirical findings from the SciTS literature, which center around five key themes: the value of TS, team composition and its influence on TS performance, formation of science teams, team processes central to effective team functioning, and institutional influences on TS. Cross-cutting issues are discussed in the context of new research opportunities to further advance SciTS evidence and better inform policies and practices for effective TS. (PsycINFO Database Record PMID- 29792468 TI - Teamwork and collaboration in long-duration space missions: Going to extremes. AB - The scientific study of teamwork in the context of spaceflight has uncovered a considerable amount of knowledge over the past 20 years. Although much is known about the underlying factors and processes of teamwork, much is left to be discovered for teams who will be operating in extreme isolation and confinement during a future Mars mission. Special considerations must be made to enhance teamwork and team well-being for multi-year missions during which the small team will live and work together. We discuss the unique challenges of effective teamwork in a Mars mission scenario, and the difficulties of studying teamwork using analogs of the space environment. We then describe the National Aeronautics and Space Administration's current practices and research on teamwork, which includes team selection and composition, teamwork training, countermeasures to mitigate risks to effective team performance, and the measurement and monitoring of team functioning. We end with a discussion of the teamwork research areas that are most critical for a successful journey to Mars. (PsycINFO Database Record PMID- 29792467 TI - Interdisciplinary team science and the public: Steps toward a participatory team science. AB - Interdisciplinary team science involves research collaboration among investigators from different disciplines who work interdependently to share leadership and responsibility. Although over the past several decades there has been an increase in knowledge produced by science teams, the public has not been meaningfully engaged in this process. We argue that contemporary changes in how science is understood and practiced offer an opportunity to reconsider engaging the public as active participants on teams and coin the term participatory team science to describe public engagement in team science. We discuss how public engagement can enhance knowledge within the team to address complex problems and suggest a different organizing framework for team science that aligns better with how teams operate and with participatory approaches to research. We also summarize work on public engagement in science, describe opportunities for various types of engagement, and provide an example of participatory team science carried out across research phases. We conclude by discussing implications of participatory team science for psychology, including changing the default when assembling an interdisciplinary science team by identifying meaningful roles for public engagement through participatory team science. (PsycINFO Database Record PMID- 29792469 TI - Unpacking team process dynamics and emergent phenomena: Challenges, conceptual advances, and innovative methods. AB - Psychologists have studied small-group and team effectiveness for decades, and although there has been considerable progress, there remain significant challenges. Meta-analyses and systematic research have provided solid evidence for core team cognitive, motivational, affective, and behavioral processes that contribute to team effectiveness and empirical support for interventions that enhance team processes (e.g., team design, composition, training, and leadership); there has been substantial evidence for a science of team effectiveness. Nonetheless, there have also been concerns that team processes, which are inherently dynamic, have primarily been assessed as static constructs. Team-level processes and outcomes are multilevel phenomena that emerge, bottom-up from the interactions among team members over time, under the shifting demands of a work context. Thus, theoretical development that appropriately conceptualizes the multiple levels, process dynamics, and emergence of team phenomena over time are essential to advance understanding. Moreover, these conceptual advances necessitate innovative research methodologies to better capture team process dynamics. We explicate this foundation and then describe 2 promising streams of scientific inquiry-team interaction sensors and computational modeling-that are advancing new, unobtrusive measurement techniques and process-oriented research methods focused on understanding the dynamics of cohesion and cognition in teamwork. These are distinct lines of research, each endeavoring to advance the science, but doing so through the development of very different methodologies. We close by discussing the near-term research challenges and the potential long-term evolution of these innovative methods, with an eye toward the future for process oriented theory and research on team effectiveness. (PsycINFO Database Record PMID- 29792470 TI - The science of teamwork: Progress, reflections, and the road ahead. AB - We need teams in nearly every aspect of our lives (e.g., hospitals, schools, flight decks, nuclear power plants, oil rigs, the military, and corporate offices). Nearly a century of psychological science has uncovered extensive knowledge about team-related processes and outcomes. In this article, we draw from the reviews and articles of this special issue to identify 10 key reflections that have arisen in the team literature, briefly summarized here. Team researchers have developed many theories surrounding the multilayered aspects of teams, such that now we have a solid theoretical basis for teams. We have recognized that the collective is often stronger than the individual, initiating the shift from individual tasks to team tasks. All teams are not created equal, so it is important to consider the context to understand relevant team dynamics and outcomes, but sometimes teams performing in different contexts are more similar than not. It is critical to have teamwork-supportive organizational conditions and environments where psychological safety can flourish and be a mechanism to resolve conflicts, ensure safety, mitigate errors, learn, and improve performance. There are also helpful teamwork competencies that can increase effectiveness across teams or tasks that have been identified (e.g., coordination, communication, and adaptability). Even if a team is made up of experts, it can still fail if they do not know how to cooperate, coordinate, and communicate well together. To ensure the improvement and maintenance of effective team functioning, the organization must implement team development interventions and evaluate relevant team outcomes with robust diagnostic measurement. We conclude with 3 main directions for scientists to expand upon in the future: (a) address issues with technology to make further improvements in team assessment, (b) learn more about multiteam systems, and (c) bridge the gap between theory and practice. In summary, the science of teams has made substantial progress but still has plenty of room for advancement. (PsycINFO Database Record PMID- 29792471 TI - Sex differences in the anorexigenic effects of dexfenfluramine and amphetamine in baboons. AB - The anorexigenic effects of intramuscular d-amphetamine HCl (0.06-0.50 mg/kg) and dexfenfluramine HCl (0.25-2.0 mg/kg) were determined in experimentally naive baboons. A group of 8 adult male baboons was tested prior to a group of 7 adult female baboons. A 120-min session occurred at 9:00 a.m. during which baboons could respond for food pellets. Drug was given 30 min prior to the 9:00 a.m. morning session. Beginning at 11:00 a.m., baboons had a 6-hr multiple-meal session during which they could have up to 4 food pellet meals. Food was not available overnight, but food was available for 90 min upon awakening such that drug effects were evaluated in non-food-deprived animals. Under baseline conditions baboons earned between 30 and 70 pellets during the morning session and another 175-225 pellets during the remainder of the day. Amphetamine and dexfenfluramine produced dose-dependent decreases in food pellet intake during both the morning food session and the later multiple-meal session. Whereas there were minimal sex differences in the effects of dexfenfluramine, many of the amphetamine doses produced greater decreases in pellet intake in males than females. These results are discordant with much of the rodent literature on abuse related drug effects that generally reports greater effects of amphetamine in females than males. Additional work is needed to replicate the current findings in nonhuman primates. (PsycINFO Database Record PMID- 29792473 TI - Cognitive and affective associations with an ecologically valid test of theory of mind across the lifespan. AB - OBJECTIVES: Many studies have demonstrated that theory of mind (ToM) ability declines with increasing age. Research has found that ToM-age associations are often mediated by other cognitive abilities particularly executive function. However, older adults rarely complain about real-world ToM difficulties. It has been suggested that older adults may perform better in real-world situations compared with experimental settings. METHOD: We examined performance on the Strange Stories Film Task (SSFT) which has been designed to assess ToM using naturalistic, video scenarios. Sixty adults aged between 17- and 95-years-old completed the SSFT, inhibitory control (Stroop) and working memory (letter-number sequencing) measures, the basic empathy scale (cognitive and affective empathy), and the broad autism phenotype questionnaire. RESULTS: ToM performance correlated significantly with age, whereas performance on a control task did not. Partial correlations and stepwise regression analyses demonstrated that performance on the three SSFT ToM measures was explained by a combination of executive function and empathy measures, with age explaining none of the variance. CONCLUSIONS: Using a naturalistic test of ToM, performance was shown to decline with age for ToM but not control scenarios. Across the lifespan, the variance in ToM performance was explained by cognitive abilities and empathy but not age. Age alone may not influence ToM ability, but may be associated with age-related changes in cognition and social-cognition. (PsycINFO Database Record PMID- 29792474 TI - Obsessive-compulsive disorder in the Veterans Health Administration. AB - Little is known about the diagnosis and treatment of obsessive-compulsive disorder (OCD) in the Veterans Health Administration (VHA). This study examined diagnostic rates of OCD in a national sample of veterans as well as clinical comorbidities and mental health service use following an OCD diagnosis. This study used administrative data extracted from VHA medical records to identify patients with an OCD diagnosis between 2010 and 2011 (N = 20,364). Descriptive analyses examined demographic, clinical, and system-level variables associated with OCD diagnosis as well as mental health service use in a subset of patients newly diagnosed with OCD (n = 5,229). The OCD diagnosis rate in VHA medical records was 0.31% of VHA patients seen in 2010-2011. Examination of new-onset OCD diagnoses in 2010-2011 revealed that OCD was most likely to be diagnosed by physicians (48.6%) and behavioral health providers (31.9%), predominantly in mental health settings (87.5%). In the year following OCD diagnosis, veterans had an average of 3.9 individual psychotherapy and 3.5 psychiatric medication visits. These findings suggest that OCD is likely underrecognized and inadequately treated in the VHA and highlight the need for improved diagnostic and treatment services for veterans with OCD. (PsycINFO Database Record PMID- 29792472 TI - Effects of exercise on experimentally manipulated craving for cannabis: A preliminary study. AB - Cannabis is the most commonly used illicit drug in the United States, and craving for cannabis is related to cannabis use. Exercise has been demonstrated to reduce craving for substances. To examine the effects of exercise on cannabis craving, we conducted a 3-week within-subject crossover experiment. Young-adult men (n = 35) and women (n = 11), age 18-25 years (M = 20.76, SD = 1.68), who regularly (>=3 times per week) used cannabis participated in a cue exposure paradigm to stimulate craving. After each of three separate craving inductions, they completed a 10-min bout of exercise that varied in intensity (rest, moderate, vigorous). Craving was assessed before and after the induction, immediately following the exercise, and at three 10-min intervals (total of 30 min). Results of condition-specific, repeated measures analyses of variance showed nonsignificant reductions in immediate postexercise craving for the moderate and vigorous conditions. We used latent growth modeling to examine the trajectory of craving rebound during the 30 min following exercise and explored the effect of baseline weekly cannabis use in predicting craving rebound. Within 30 min postexercise, craving rebounded for both the moderate, F(3, 135) = 9.10, p < .01, and vigorous, F(3, 135) = 3.48, p < .05, conditions. We found that among cannabis users reporting larger quantities of typical weekly cannabis use, craving rebounded more quickly following vigorous than moderate exercise, b = 0.02, SE = 0.02, 95% confidence interval [0.00, 0.06]. The findings suggest that moderate exercise may be useful for reducing craving, particularly among those who use larger quantities of cannabis. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792475 TI - The alliance in adult psychotherapy: A meta-analytic synthesis. AB - The alliance continues to be one of the most investigated variables related to success in psychotherapy irrespective of theoretical orientation. We define and illustrate the alliance (also conceptualized as therapeutic alliance, helping alliance, or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients (published between 1978 and 2017) for face-to-face and Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using a three-level meta analysis with random-effects restricted maximum-likelihood estimators. The overall alliance-outcome association for face-to-face psychotherapy was r = .278 (95% confidence intervals [.256, .299], p < .0001; equivalent of d = .579). There was heterogeneity among the effect sizes, and 2% of the 295 effect sizes indicated negative correlations. The correlation for Internet-based psychotherapy was approximately the same (viz., r = .275, k = 23). These results confirm the robustness of the positive relation between the alliance and outcome. This relation remains consistent across assessor perspectives, alliance and outcome measures, treatment approaches, patient characteristics, and countries. The article concludes with causality considerations, research limitations, diversity considerations, and therapeutic practices. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792476 TI - A mixed-methods investigation into the perspectives on mental health and professional treatment among former system youth with mood disorders. AB - Research has shown that how people think about their health (or illnesses) shapes their help-seeking behavior. In this mixed-methods study, we employed a simultaneous concurrent design to explore the perceptions of mental illness among an understudied population: marginalized young adults. Participants were 60 young adults (ages 18-25) who had experienced mood disorders and used multiple public systems of care during their childhoods. Semistructured interviews were conducted to understand participants' illness and treatment experiences during the transition to adulthood. A team of analysts used constant comparison to develop a codebook of the qualitative themes, and quantitative data were examined using SAS 9.3. Findings suggest that some theoretical categories identified in past illness perceptions frameworks are salient to marginalized young adults (e.g., identity, management-or control-of symptoms), but both the developmental transition to adulthood and experiences with public systems of care add nuanced variations to illness and treatment perceptions. Our study demonstrates that young adults possess a set of beliefs and emotions about their mental health and help-seeking options that need to be better understood to improve engagement and quality of mental health care for this population. Implications for practice, research, and policy are discussed. (PsycINFO Database Record PMID- 29792477 TI - Psychological adjustment in Spanish young adult domestic adoptees: Mental health and licit substance consumption. AB - Although adoptive families have been shown to provide a protective context for human development, some adopted children and adolescents are at increased risk for psychological adjustment problems. On the other hand, little is known about psychological adjustment of young adult adoptees. The aim of this study is to analyze the mental health and legal substance consumption (tobacco and alcohol) of young adults (n = 134) who were domestically adopted by Spanish families. Young adults showed significantly worse scores on the Symptom Check-List-90-R (Derogatis, 1975) and also more substance use than did the Spanish general population, but fewer difficulties than did the clinical population. On the Global Severity Index (GSI), 65.7% of adoptees were within the normal range, 24.6% were at risk, and 9.7% were within the clinical range. Male adoptees scored higher than expected for the general population on all subscales, whereas female adoptees did not. Age at adoption was not found to have a significant impact on adjustment. (PsycINFO Database Record PMID- 29792478 TI - Acculturation in the discourse of immigrants and receiving community members: Results from a cross-national qualitative study. AB - This study explores the bidirectional and interactional process of acculturation from the perspectives of immigrants and receiving community members (RCMs). Our aim was to understand the experiences and interactions of different ethno cultural groups and their impact on the functioning and dynamics of multicultural communities. We conducted a cross-national, cross-cultural study of acculturation processes, using interviews collected across two countries (Italy: urban regions of Torino and Lecce; U.S.: Baltimore/Washington corridor) and three distinct groups of immigrants-Moroccans and Albanians in Italy and Latin Americans in the United States-and RCMs in Italy and the United States. Findings show that acculturation is a complex, situated, and dynamic process, and is generally conceived as an unbalanced and individual process of accommodation, which expects the immigrant alone to adapt to the new context. The boundaries among traditionally explored acculturation strategies were blurred and while integration was the most frequently discussed strategy, it often referenced a "soft" assimilation, limited mostly to public domains. Some differences emerged between ethnic groups and generation of immigration as well as among RCMs who differed by level of contact with immigrants. The need for more flexible models and for a critical perspective on acculturation is discussed. (PsycINFO Database Record PMID- 29792479 TI - "Fewer but not weaker": Understanding the intersectional identities among Chinese immigrant young gay men in Toronto. AB - Sexual minorities of color in North America are frequently defined as a "double minority" group. Intersectionality theory has inspired investigations into how different forms of marginalization intersect to shape the lives of people with multiple minority statuses. In this constructivist grounded theory study, 18 Chinese immigrant gay men between 18 and 28 years of age participated in a semistructured individual interview to narrate their lived experiences in relation to their intersectional identities. All interviews were transcribed verbatim and analyzed through a constant comparative method. Several themes emerged from the data. First, study participants perceived their sexual identity as either compatible with or irrelevant to their cultural identity and did not experience negotiating conflicts between their sexual and cultural identities. Second, the intersectionality was context-specific. Study participants experienced a certain form of marginalization in the contexts of disclosing their gay identity and finding a dating partner within a gay community. Third, participants considered the label double minority oversimplified and derogatory. They emphasized that their daily lives were in a complex power structure that was constituted by more than two identity categories. The marginalization based on their ethnic and sexual identities weighed differently and should not be understood as simple math. Last, despite carrying the status of minority, these gay men indicated that their intersectional identities served as a source of social support. This study contributes to the knowledge base around intersectionality by uncovering its qualitative nuance and bringing to light its contextual specificity. Practice, policy, and research implications are provided. (PsycINFO Database Record PMID- 29792480 TI - The impact of familial expressed emotion on clinical and personal recovery among patients with psychiatric disorders: The mediating roles of self-stigma content and process. AB - The present study examined the associations of familial expressed emotion (EE) with clinical and personal recovery among patients with psychiatric disorders, as well as the potential mechanisms underlying these associations. Guided by the content-process theory of self-stigma, we hypothesized that EE would be negatively associated with clinical and personal recovery and that these associations would be mediated by self-stigma content and process. A total of 311 patients with psychiatric disorders completed questionnaires on their perceptions of EE, self-stigma, and recovery. Structural equation modeling demonstrated that EE was positively associated with self-stigma content and process, which were in turn negatively associated with clinical and personal recovery. The indirect effects of EE on clinical and personal recovery, via self-stigma content and process, were also significant. Multigroup analyses further demonstrated that the impact of EE on self-stigma and recovery was generalizable across patients with psychotic and nonpsychotic disorders. Theoretically, our findings revealed the potential pathways through which EE may adversely affect psychiatric recovery. Practically, our findings highlighted the importance of designing multipronged intervention programs to reduce familial EE and its potential harmful impact on psychiatric patients. In addition to helping family members improve their knowledge about psychiatric disorders and adjust their communication styles, practitioners should help psychiatric patients develop resilience against EE, mitigate self-stigma, and achieve recovery. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792482 TI - Discrimination and externalizing problems among Moroccan- and Romanian-origin early adolescents in Italy: Moderating role of cultural orientations and impulse control. AB - OBJECTIVE: Although discrimination is a common stressor in the everyday life of immigrant youth, individuals are not equally susceptible to its adverse effects. This cross-sectional study aimed to examine whether cultural orientation preferences and impulse control (IC) moderate the association between perceived discrimination and externalizing problems among Moroccan- and Romanian-origin early adolescents in Italy. METHOD: The sample included 126 Moroccan and 126 Romanian youths (46% girls, 42% first-generation) aged 11-13 years and their parents. Perceived discrimination and cultural orientations were assessed using self-report questionnaires, while IC was evaluated via a computerized version of the Iowa Gambling Task. Externalizing behaviors were assessed via parental report. RESULTS: Cluster analysis identified separated, assimilated, and integrated early adolescents. Regression analyses revealed that when facing discrimination, youths who endorsed separation and exhibited low levels of IC were more vulnerable to externalizing problems. In contrast, among assimilated adolescents the discrimination-externalizing difficulties link was significant at high levels of IC. Furthermore, low levels of IC were associated with more externalizing problems for Romanian, but not for Moroccan early adolescents. CONCLUSIONS: Findings underscore the need to consider both cultural orientation processes and early adolescents' ability to control their impulses when developing interventions aimed to reduce discrimination-related problem behaviors in immigrant youth. Implications for theory and practice are discussed. (PsycINFO Database Record PMID- 29792481 TI - Risk and protective factors of intimate partner violence among South Asian immigrant women and perceived need for services. AB - OBJECTIVES: Limited research exists on multilevel influences of intimate partner violence (IPV) among immigrant groups in the United States, particularly South Asians. Using a socioecological framework, this study examined risk and protective factors of IPV among a diverse group of South Asian immigrant survivors of IPV and identified their perceived need for services. METHOD: Sixteen South Asian immigrant survivors were recruited from New York; Maryland; Virginia; and Washington, DC, using a snowball sampling method. Participants were 1st-generation and 2nd-generation immigrants born in India (n = 4), Bangladesh (n = 4), Pakistan (n = 5), the United States (n = 2), and Sri Lanka (n = 1). Data were collected using in-depth interviews (n = 16) and a focus group (n = 1). A thematic analysis procedure was used to analyze the data and to identify themes across different ecological levels. RESULTS: IPV was related to factors at multiple levels, such as cultural normalization of abuse, gender role expectations, need to protect family honor, arranged marriage system, abusive partner characteristics, and women's fear of losing children and being on own. Protective factors included supportive family and friends, religion, safety strategies, education, and empowerment. Women highlighted the need for community education and empowerment efforts and culturally responsive services for addressing IPV in South Asian communities. CONCLUSIONS: South Asian survivors of IPV have experienced, and some continue to experience, abuse due to factors operating at multiple levels of the ecological framework. Consideration of culturally specific risk and protective factors for IPV at multiple contexts in women's lives could inform culturally responsive IPV prevention and intervention strategies for South Asian communities in the United States. (PsycINFO Database Record PMID- 29792484 TI - "A threat on the ground": The consequences of witnessing stereotype-confirming ingroup members in interracial interactions. AB - OBJECTIVES: Three studies explored interpersonal consequences of engaging in interracial interactions after witnessing racial ingroup members' stereotypical behavior. METHOD: Study 1 used experience-sampling methodology to assess ethnic minority students' (n = 119) intergroup anxiety, metastereotypes, and anticipatory behaviors following one of three types of interpersonal interactions: (a) a White person and a racial ingroup member who had behaved stereotypically, (b) a White person and a nonstereotypical ingroup member, or (c) neither. Studies 2 (n = 273) and 3 (n = 379) experimentally examined whether witnessing an ingroup member's stereotypically negative behavior in interracial interactions, compared to stereotypically positive (Study 2) or nonstereotypically negative behavior (Study 3) differentially affected anxiety, metastereotypes, and anticipatory behaviors in interracial versus intraracial interactions among Black Americans. RESULTS: In Study 1, minorities reported greater anxiety, metastereotypes, and motivation to disprove stereotypes, but less interest in future interracial contact, following interracial interactions involving stereotype-confirming ingroup members compared to other interactions. In Studies 2 and 3, adverse interaction consequences were most severe when ingroup behavior was both negative and stereotypical compared to neutral, stereotypically positive, and nonstereotypically negative ingroup behavior. Additionally, metastereotypes (and, to a lesser degree, anxiety) mediated individuals' motivation to disprove stereotypes and desire future interactions with White witnesses following stereotypically negative ingroup behavior in interracial (vs. intraracial) interactions. CONCLUSIONS: This research highlights the emotional, metaperceptual, and motivational outcomes following ingroup members' stereotypical behavior in intergroup contexts that extend beyond dyadic encounters. (PsycINFO Database Record PMID- 29792483 TI - When anger expression might be beneficial for African Americans: The moderating role of chronic discrimination. AB - OBJECTIVES: Anger expression is assumed to have mostly negative health effects. Yet, evidence is mixed on how anger expression influences African Americans' cardiovascular health. The present research aimed to clarify this link by examining moderating effects of chronic discrimination on the relationship between anger expression and cardiovascular risk among African Americans in experimental (Study 1) and epidemiological (Study 2) studies. METHOD: Study 1 examined how African Americans' trait anger expression was linked to (a) physiologic reactivity to acute social rejection during an interracial encounter (Session 1); and (b) total/HDL cholesterol assessed two months later (Session 2). Study 2 examined the relationship between anger expression and total/HDL cholesterol with a larger sample of African Americans from the Midlife in the United States (MIDUS) survey. Both studies examined perceptions of chronic discrimination as a moderator of the relationships between anger expression and biological responses. RESULTS: In Study 1 higher anger expression was associated with quicker cortisol recovery and greater testosterone reactivity following outgroup social rejection in Session 1 and lower total/HDL cholesterol in Session 2. Study 2 replicated the relationship between anger expression and lower total/HDL cholesterol and further showed that this relationship was unique to the expressive aspect of anger. Importantly, in both studies, these potentially beneficial effects of anger expression were only evident among individuals with lower perceptions of chronic discrimination. CONCLUSIONS: These findings suggest that anger expression, when coupled with low levels of chronic discrimination, is associated with adaptive patterns of physiologic responses among African Americans. (PsycINFO Database Record PMID- 29792486 TI - Okay to say?: Initial validation of the Acceptability of Racial Microaggressions Scale. AB - : Despite a growing body of research documenting the negative impact of racial microaggressions on racial and ethnic minorities' wellbeing, there remains debate in society about whether it is acceptable to say racially microaggressive statements. However, no scale exists to assess attitudes about the acceptability of saying such statements. OBJECTIVES: In this study we present an initial validation of a new scale, the Acceptability of Racial Microaggressions Scale (ARMS), which assesses attitudes about how "okay" it is for White individuals to say different types of racially microaggressive statements to racial and ethnic minorities in an interpersonal interaction. METHOD AND RESULTS: We provide exploratory (Study 1; n = 596) and confirmatory (Study 2; n = 404) factor analytic support for the presence of four factors regarding acceptability of saying different types of microaggressive statements: Victim Blaming, Color Evasion, Power Evasion, and Exoticizing. We present evidence for construct validity by testing associations with several race-related, ideological, and personality measures. We provide evidence in Study 3 (n = 90) for test-retest reliability over a 2-week time period, and show associations between attitudes toward acceptability and self-reported likelihood of personal commission. CONCLUSIONS: Overall, we provide initial psychometric and validity evidence for the ARMS and discuss implications and potential uses of the scale. (PsycINFO Database Record PMID- 29792487 TI - Ethnic-racial typicality and its relation to ethnic identity and psychological functioning. AB - OBJECTIVES: Ethnic identity development is considered a central task of adolescence and emerging adulthood for ethnic minority individuals. Although the process of developing a coherent ethnic identity has received attention from researchers, there has been little work done to elucidate the content of ethnic identity. This study uses an inductive mixed-methods approach to address 1 aspect of ethnic identity content: typicality, or the degree of perceived similarity individuals feel to their ethnic-racial group. METHOD: Participants included 974 college students at 3 universities-66% women, average age 20.4 years, 5% Black, 30% Asian, 10% Latinx, 40% White, 11% Multiracial, 1% American Indian, and 4% Other race-ethnicity. Thematic analysis was used to code qualitative categories on what makes individuals typical of and atypical of their ethnic group. Codes were used to quantitatively assess relations between aspects of typicality, ethnic identity, and mental health. RESULTS: Findings suggest that individuals judged their typicality and atypicality to their ethnic group by focusing on skin color, hair, facial features; values related to family, achievement, and religion spirituality; and behaviors related to arts-media, sports, spending time with others, and food. Additionally, findings demonstrated that most individuals feel typical of their ethnic group and, of importance, that level of perceived typicality was inversely related to measures of ethnic identity and well-being. Finally, participants differed in their feeling of being typical by ethnic-racial group identifications. CONCLUSIONS: Ethnic-racial typicality provides valuable information about ethnic identity content and is related to important mental health outcomes. (PsycINFO Database Record PMID- 29792488 TI - Asian Americans and materialism: Exploring the phenomenon and its why and when. AB - OBJECTIVES: Consumer values, including but not limited to materialism, have received much less attention than other topics within research on Asian Americans. METHODS: Across 3 studies (N = 6,955), the author explored the difference between Asian Americans and White/European Americans on materialism, and the mediating and moderating mechanisms. RESULTS: Studies 1a-1c found Asian Americans, compared to White/European Americans, more strongly endorsed materialistic values. In Study 2, the author tested a multiple mediation model and demonstrated that Asian Americans, compared to White/European Americans, more strongly endorse materialistic values because they reported higher extrinsic aspirations (i.e., stronger desires for money, image, and popularity). Finally, in Study 3, the author tested a moderation model and found that Asian Americans who are higher on a general tendency to adhere to norms endorse a greater level of materialism than White/European Americans. CONCLUSIONS: The author discussed how these results have implications for expanding the research topics within research on Asian Americans, consequences for mental health and provide future directions to counteract materialism. (PsycINFO Database Record PMID- 29792485 TI - Telephone-assisted, parent-mediated CBT for rural Latino youth with anxiety: A feasibility trial. AB - OBJECTIVE: In this study, we tailor a child anxiety cognitive-behavior therapy (CBT) program to fit the needs of rural Latino/a Spanish-speaking families and examine the feasibility, acceptability, tolerability, and safety of this intervention using 2 modes of service delivery. METHOD: Children (n = 31; age 8 13) with anxiety disorders were recruited from primary care settings and randomized to 1 of 2 modes of parent-mediated CBT bibliotherapy: (1) telephone delivered, therapist-assisted bibliotherapy (TTB; n = 15), and (2) a more minimal contact, self-directed, bibliotherapy condition (SB; n = 16). Independent evaluators administered a diagnostic interview at baseline and posttreatment; demographic and engagement-related questionnaires were also administered. RESULTS: In the TTB group, 10 of 15 parents (66.7%) completed the requisite number of therapist-assisted bibliotherapy sessions, and in the SB group, 4 of 16 parents (25%) completed the requisite number of self-directed bibliotherapy modules; this comparison was significant, chi2(1) = 5.43, p = .02. In the TTB condition, treatment length and session duration were longer than reported in previous studies. Barriers that were most strongly endorsed were stressors and obstacles competing with treatment, as well as treatment demandingness. Findings revealed good satisfaction across the conditions, although ratings were significantly higher in the TTB group, F = 5.67, p = .028. Remission rates (i.e., no anxiety disorder) for those that provided posttreatment data (N = 25) were 50% and 36% for the TTB and SB groups, respectively, chi2(1) = .465, p = .50. CONCLUSIONS: Implications of these feasibility findings and suggestions for future research are discussed. (clinicaltrials.gov unique identifier: NCT01491880). (PsycINFO Database Record PMID- 29792489 TI - What it means to be a national: A study among adolescents in multicultural Mauritius. AB - OBJECTIVES: We investigated adolescents' understandings of national group membership in multicultural Mauritius. We hypothesized that tolerance toward different cultures would be an important criterion for being Mauritian. In addition, national identity was expected to be defined in terms of "being," "feeling," and "doing." The type of definition, and whether stopping being Mauritian is perceived as possible, was expected to depend on age and national identification. Possible differences by cultural group membership were explored. METHOD: The sample consisted of 2,190 adolescents of predominantly the three main cultural groups in Mauritius (Hindus, Muslims, and Creoles; Mage = 14.8 years, SDage = 1.7; 53% girls, 47% boys). Multiple correspondence and regression analyses were used to test the hypotheses. RESULTS: The most important criterion mentioned for being Mauritian was respecting cultural diversity. Further, the criteria for national belonging could be clustered into being, feeling, and doing Mauritian. Older adolescents and higher national identifiers defined national belonging more in terms of feeling and less in terms of being than younger adolescents and lower national identifiers. In addition, they considered national identity to be less changeable. There were no clear differences between the three cultural groups. CONCLUSIONS: This study reveals the central importance of mutual respect and tolerance as the defining criterion for being Mauritian. Moreover, the feeling, being, and doing clusters of criteria provide a theoretically interesting distinction for understanding national belonging. It is recommended to test their possible correlates further and to use adult samples as well. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792490 TI - Generalizability of a traditional social cognitive model of prosocial behaviors to U.S. Latino/a youth. AB - OBJECTIVES: We hypothesized that parental and peer support, empathy-related traits, and prosocial moral reasoning would positively predict altruistic prosocial behaviors, and negatively predict selfish-motivated prosocial behaviors, in U.S. Latino youth. METHOD: Three-hundred and 6 U.S. Latina/o adolescents (M age = 15.50 years; SD = .42 years; 46% girls; 81.0% self identified as U.S. Mexican) from communities in the Northern Great Plains completed measures of parental and peer support, perspective taking and empathic concern, prosocial moral reasoning, and two types of prosocial behaviors. RESULTS: In general, parental support was directly and indirectly related to empathic traits, prosocial moral reasoning, and prosocial behaviors. Peer support was indirectly related to prosocial behaviors via perspective taking, empathic concern, and prosocial moral reasoning. CONCLUSIONS: Discussion focuses on the generalizability of traditional models of moral socialization and prosocial development to U.S. Latina/o youth from communities in the Northern Great Plains. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792491 TI - Does oral language underpin the development of later behavior problems? A longitudinal meta-analysis. AB - OBJECTIVE: The purpose of this article is to estimate the overall weighted mean effect of the relation between early language skills and later behavior problems in school-aged children. METHOD: A systematic literature search yielded 19,790 unduplicated reports, and a structured search strategy and identification procedure yielded 25 unique data sets, with 114 effect sizes for analysis. Eligible reports were then coded, and effect sizes were extracted and synthesized via robust variance estimation and random-effects meta-analytic techniques. RESULTS: The overall correlation between early language and later behavior problems was negative and small (r = -.14, 95% confidence interval [CI] [-.16, .11]), and controlling for demographic variables did not reduce the magnitude of the inverse relationship between language skill and problem behavior (r = -.16). Moderator analyses identified receptive language, parent-reported behavior measures, gender, and age as significant predictors of the association between language and behavior. CONCLUSION: This article corroborates the consistent findings of previous meta-analytic and longitudinal studies and further identifies areas, particularly around measurement, for future research. Furthermore, prospective longitudinal evaluations of the relations between language deficits and behavior problems with different types of measures (teacher /parent-report, direct assessment, classroom observation) is warranted. (PsycINFO Database Record PMID- 29792492 TI - Evaluation of second step on early elementary students' academic outcomes: A randomized controlled trial. AB - Research has consistently linked social-emotional learning to important educational and life outcomes. Early elementary represents an opportune developmental period to proactively support children to acquire social-emotional skills that enable academic success. Using data from a large scale randomized controlled trial, the purpose of this study was to investigate the impact of the 4th edition of Second Step on early elementary students' academic-related outcomes. Participants were Kindergarten to 2nd grade students in 61 schools (310 teachers; 7,419 students) across six school districts in Washington State and Arizona. Multilevel models (Time * Condition) indicated the program had no positive main effect impact on academic outcomes. However, moderator analyses revealed that quality of implementation, specifically a measure of student engagement and dosage, was found to be associated with significant, albeit small, reading and classroom behavior outcomes. Findings from this study provide support for Second Step when implemented in the context of high engagement and higher dosage to have small but potentially meaningful collateral impact on early academic-related outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792493 TI - Does increased effort compensate for performance debilitating test anxiety? AB - It is well established that test anxiety is negatively related to examination performance. Based on attentional control theory, the aim of this study was to examine whether increased effort can protect against performance debilitating test anxiety. Four hundred and sixty-six participants (male = 228; 48.9%; White = 346, 74.3%; mean age = 15.7 years) completed self-report measures of test anxiety and effort that were matched to performance on a high-stakes secondary school examination. The worry and bodily symptoms components of test anxiety were negatively, and effort, positively related to examination performance. Effort moderated the negative relation between bodily symptoms and examination performance. At low effort, the negative relationship was amplified and at high effort was attenuated. Compensatory effort protects performance against bodily symptoms but not worry. It is possible that the cognitive load on working memory arising from the combination of worry and examination demands may be too high to be compensated by effort. (PsycINFO Database Record PMID- 29792494 TI - Fostering youth self-efficacy to address transgender and racial diversity issues: The role of gay-straight alliances. AB - Gay-Straight Alliances (GSAs) aspire to empower youth to address multiple systems of oppression, including those affecting transgender and racial/ethnic minority youth, yet there is little indication of factors contributing to youths' self efficacy to do so. We examined individual and group factors predicting self efficacy to address transgender and racial issues among 295 youth in 33 high school GSAs. Multilevel results indicated that level of GSA engagement, individual and collective involvement in transgender- and race-specific discussions, and in some cases intergroup friendships were associated with each form of self-efficacy. The association between GSA engagement and transgender self-efficacy was stronger for youth in GSAs with greater collective transgender specific discussions. Associations with racial self-efficacy differed based on youths' race/ethnicity. Continued research needs to identify how GSAs and similar youth programs promote self-efficacy to address diversity issues. (PsycINFO Database Record PMID- 29792495 TI - First grade classroom-level adversity: Associations with teaching practices, academic skills, and executive functioning. AB - Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development and a model-building approach, the authors examined direct and indirect associations between first-grade (G1) classroom-level adversity (CLA), G1 teaching practices, and student (N = 1,073; M = 6.64 years; 49% girls; 82% White) academic skills and executive functioning in G1 and third grades (G3). Teachers reported the prevalence of adversity among their students (e.g., poor home/family life, poor academic/social readiness). Observers rated G1 teaching practices: teachers' classroom management, controlling instruction, and amount of academic instruction (classroom observation system). Children completed literacy and math assessments at 54 months, G1, and G3 (Woodcock Johnson Letter-Word Identification and Applied Problems), and executive functioning at G1 and G3 (Tower of Hanoi). Direct associations emerged between CLA and controlling instruction (positive), classroom management, and academic instruction (both negative). In addition, CLA was related to G1 literacy (but not math) directly and indirectly via classroom management (negatively) and controlling instruction (positively). The addition of G3 outcomes revealed a negative direct longitudinal association between CLA and G3 executive functioning, and indirect associations with G3 literacy and math through G1 teaching practices and literacy. Results support the notion that collective student characteristics influence student outcomes in part through teaching practices and suggest that teachers and students may benefit from the diffusion of high-adversity classroom compositions when possible. Moreover, in high-adversity classrooms teachers and students may benefit from supports targeting classroom management and foundational student competencies. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792496 TI - The big two personality traits and adolescents' complete mental health: The mediation role of perceived school stress. AB - Based on Greenspoon and Saklofske's (2001) dual-factor model of mental health, we defined adolescents' mental health as comprised of two distinguishable factors: positive and negative mental health. We tested the direct relations between the Eysenck's (1967) Big Two personality traits (Extraversion and Neuroticism) and positive and negative mental health, and explored the mediation effects of perceived school stress in accounting for the relations. Direct and indirect relations were estimated by using structural equation modeling with data from 1,009 Chinese adolescents in a 3-wave study. Results indicated that (a) adolescents' levels of neuroticism showed a positive relation to negative mental health and a negative relation to positive mental health, whereas levels of extraversion showed a negative relation to negative mental health and a positive relation to positive mental health; and (b) adolescents' perceived school stress (PSS) mediated the relation between neuroticism and mental health but not the relation between extraversion and mental health. The findings suggest that school professionals should consider adolescents' personality traits and school-based stress when planning and delivering mental health services. The findings of the relations between extraversion and PSS are also discussed in light of the face culture in China. (PsycINFO Database Record PMID- 29792497 TI - Examining the stability of social, emotional, and behavioral risk status: Implications for screening frequency. AB - Responsive service delivery frameworks rely on the use of screening approaches to identify students in need of support and to guide subsequent assessment and intervention efforts. However, limited empirical investigations have been directed to informing how often screening should occur for social, emotional, and behavioral difficulties in school settings. The purpose of the current study was to evaluate the stability of risk status on 3 different screening instruments across 3 administrations across the course of a school year. A total of 1,594 students had complete screening data across 3 time points, corresponding to a total of 187 teachers from 22 different public schools located within the northeastern and midwestern United States. Across measures, we examined patterns of risk across time points and investigated the utility of (a) different screening schedules (fall, winter, and spring) and (b) borderline screening when conducting multiple screenings per year. Results indicated that a large proportion of students exhibited stable risk patterns across time points and suggested that borderline screening may be a viable alternative for schools with limited resources. Implications for practice and future research are discussed. (PsycINFO Database Record PMID- 29792498 TI - Diagnostic accuracy of a universal screening multiple gating procedure: A replication study. AB - The purpose of this diagnostic accuracy study was to evaluate the sensitivity and specificity (among other indicators) of three universal screening approaches, including the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS), a SAEBRS-based teacher nomination tool, and a multiple gating procedure (MGP). Each screening approach was compared to the BASC-2 Behavioral and Emotional Screening System (BESS), which served as a criterion indicator of student social-emotional and behavioral risk. All data were collected in a concurrent fashion. Participants included 704 students (47.7% female) from four elementary schools within the Midwestern United States (21.6% were at risk per the BESS). Findings yielded support for the SAEBRS, with sensitivity = .93 (95% confidence interval [.89-.97]), specificity = .91 (.89-.93), and correct classification = .92. Findings further supported the MGP, which yielded sensitivity = .81 (.74-.87), specificity = .93 (.91-.95), and correct classification = .91. In contrast, the teacher nomination tool yielded questionable levels of diagnostic accuracy (sensitivity = .86 [.80-.91], specificity = .74 [.70-.78], and correct classification = .76). Overall, findings were particularly supportive of SAEBRS diagnostic accuracy, suggesting the MGP might also serve as an acceptable approach to universal screening. Other implications for practice and directions for future research are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792499 TI - Teacher and student race as a predictor for negative feedback during instruction. AB - There is a long and persistent gap between the academic achievement of White and Black students in America's schools. Further, Black students are suspended from school at a rate that is more than three times greater than White students. While there has been some suggestion that perhaps teacher-student racial matching may be part of a solution, the research does not currently provide adequate support for teacher race alone to be sufficiently effective. This study analyzed 41 Black and White teacher-student dyad mixes in elementary schools and another 41 in a high school to examine how teacher and student race interact in terms of teacher and student behaviors. While Black students were slightly more likely to be off task and disruptive, both Black and White teachers were found to provide significantly more negative feedback to Black students regardless of their behavior. Implications for teacher practice and future study are discussed. (PsycINFO Database Record PMID- 29792501 TI - Optimizing the length, width, and balance of a personality scale: How do internal characteristics affect external validity? AB - How well can scores on a personality scale predict criteria such as behaviors and life outcomes? This question concerns external validity, which is a core aspect of personality assessment. The present research was conducted to examine how external validity is influenced by a trait scale's internal characteristics, such as its length (number of items), width (breadth of content), and balance (between positively and negatively keyed items). Participants completed the Big Five Inventory-2 (BFI-2), and were also assessed on a set of self-reported and peer reported validity criteria. We used the BFI-2 item pool to construct multiple versions, or iterations, of each Big Five trait scale that varied in terms of length, width, and balance. We then identified systematic effects of these internal scale characteristics on external validity associations. Regarding length, we find that longer trait scales tend to have greater validity, with a scale length "sweet spot" of approximately 6 to 9 items. Regarding width, we find that broad trait scales tend to have slightly stronger, and much more consistent, associations with external validity criteria than do narrow scales; broad scales thus represent relatively safe bets for personality assessment, whereas narrow scales carry greater risks but offer potentially greater rewards. Regarding balance, we find that associations between imbalanced trait and criterion scales can be substantially inflated or suppressed by acquiescent responding; trait scales that include an equal number of positively and negatively keyed items can minimize such acquiescence bias. We conclude by translating these findings into practical advice regarding psychological assessment. (PsycINFO Database Record PMID- 29792500 TI - The Perceived Invalidation of Emotion Scale (PIES): Development and psychometric properties of a novel measure of current emotion invalidation. AB - Emotion invalidation is theoretically and empirically associated with mental and physical health problems. However, existing measures of invalidation focus on past (e.g., childhood) invalidation and/or do not specifically emphasize invalidation of emotion. In this article, the authors articulate a clarified operational definition of emotion invalidation and use that definition as the foundation for development of a new measure of current perceived emotion invalidation across a series of five studies. Study 1 was a qualitative investigation of people's experiences with emotional invalidation from which we generated items. An initial item pool was vetted by expert reviewers in Study 2 and examined via exploratory factor analysis in Study 3 within both college student and online samples. The scale was reduced to 10 items via confirmatory factor analysis in Study 4, resulting in a brief but psychometrically promising measure, the Perceived Invalidation of Emotion Scale (PIES). A short-term longitudinal investigation (Study 5) revealed that PIES scores had strong test retest reliability, and that greater perceived emotion invalidation was associated with greater emotion dysregulation, borderline features and symptoms of emotional distress. In addition, the PIES predicted changes in relational health and psychological health over a 1-month period. The current set of studies thus presents a psychometrically promising and practical measure of perceived emotion invalidation that can provide a foundation for future research in this burgeoning area. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792502 TI - Successful validation of the CAT-MH Scales in a sample of Latin American migrants in the United States and Spain. AB - We examined cultural differences in the item characteristic functions of self reported of symptoms of depression, anxiety, and mania-hypomania in a Latino population taking Computerized Adaptive Tests for Mental Health (CAT-MH) in Spanish versus a non-Latino sample taking the tests in English. We studied differential item functioning (DIF) of the most common adaptively administered symptom items out of a bank of 1,008 items between Latino (n = 1276) and non Latino (n = 798) subjects. For depression, we identified 4 items with DIF that were good discriminators for non-Latinos but poor discriminators for Latinos. These items were related to cheerfulness, life satisfaction, concentration, and fatigue. The correlation between the original calibration and a Latino-only new calibration after eliminating these items was r = .990. For anxiety, no items with DIF were identified. The correlation between the original and new calibrations was r = .993. For mania-hypomania, we identified 4 items with differential item functioning that were good discriminators for non-Latinos but poor discriminators for Latinos. These items were related to risk-taking, self assurance, and sexual activity. The correlation between the original and new calibration was r = .962. Once the identified items were removed, the correlation between the original calibration and a Latino-only calibration was r = .96 or greater. These findings reveal that the CAT-MH can be reliably used to measure depression, anxiety, and mania in Latinos taking these tests in Spanish. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792503 TI - Revisiting Carroll's survey of factor-analytic studies: Implications for the clinical assessment of intelligence. AB - [Correction Notice: An Erratum for this article was reported in Vol 30(8) of Psychological Assessment (see record 2018-37729-003). In the article "Revisiting Carroll's Survey of Factor-Analytic Studies: Implications for the Clinical Assessment of Intelligence," by Nicholas F. Benson, A. Alexander Beaujean, Ryan J. McGill, and Stefan C. Dombrowski (Psychological Assessment, Advance online publication, May 24, 2018, http://dx.doi.org/10.1037/pas0000556), the majority of values in the omegaH and omegaHS columns of Table 4 were incorrect and have been amended. These revisions required text in the fourth paragraph of the Results section to be changed from "Moreover, the omegaHS value for Gs is relatively high and very close to the and omegaH values for g" to "Moreover, the omegaHS values for Gs and Gv are relatively high, exceeding the omega and omegaH values for g." All versions of this article have been corrected.] John Carroll's three-stratum theory (and the decades of research behind its development) is foundational to the contemporary practice of intellectual assessment. The present study addresses some limitations of Carroll's work: specification, reproducibility with more modern methods, and interpretive relevance. We reanalyzed select data sets from Carroll's survey of factor analytic studies using confirmatory factor analysis as well as modern indices of interpretive relevance. For the majority of data sets, we found that Carroll likely extracted too many factors representing Stratum II abilities. Moreover, almost all factors representing Stratum II abilities had little-to-no interpretive relevance above and beyond that of general intelligence. We conclude by discussing the implications of this research with respect to the interpretive relevance and clinical utility of scores reflecting cognitive abilities at all strata of the three-stratum theory and offer some directions for future research. (PsycINFO Database Record PMID- 29792504 TI - Measurement invariance of TGMD-3 in children with and without mental and behavioral disorders. AB - This study evaluated whether the Test of Gross Motor Development 3 (TGMD-3) is a reliable tool to compare children with and without mental and behavioral disorders across gross motor skill domains. A total of 1,075 children (aged 3-11 years), 98 with mental and behavioral disorders and 977 without (typically developing), were included in the analyses. The TGMD-3 evaluates fundamental gross motor skills of children across two domains: locomotor skills and ball skills. Two independent testers simultaneously observed children's performances (agreement over 95%). Each child completed one practice and then two formal trials. Scores were recorded only during the two formal trials. Multigroup confirmatory factor analysis tested the assumption of TGMD-3 measurement invariance across disability groups. According to the magnitude of changes in root mean square error of approximation and comparative fit index between nested models, the assumption of measurement invariance across groups was valid. Loadings of the manifest indicators on locomotor and ball skills were significant (p < .001) in both groups. Item response theory analysis showed good reliability results across locomotor and the ball skills full latent traits. The present study confirmed the factorial structure of TGMD-3 and demonstrated its feasibility across normally developing children and children with mental and behavioral disorders. These findings provide new opportunities for understanding the effect of specific intervention strategies on this population. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792505 TI - A new test for the assessment of working memory in clinical settings: Validation and norming of a month ordering task. AB - Month ordering tasks have been used in experimental settings to obtain measures of working memory (WM) capacity in older/clinical groups based solely on their face validity. We sought to assess the appropriateness of using a month ordering task in other contexts, including clinical settings, as a psychometrically sound WM assessment. To this end, we constructed a month ordering task (ucMOT), studied its reliability (internal consistency and temporal stability), and gathered construct-related and criterion-related validity evidence for its use as a WM assessment. The ucMOT proved to be internally consistent and temporally stable, and analyses of the criterion-related validity evidence revealed that its scores predicted the efficiency of language comprehension processes known to depend crucially on WM resources, namely, processes involved in pronoun interpretation. Furthermore, all ucMOT items discriminated between younger and older age groups; the global scores were significantly correlated with scores on well-established WM tasks and presented lower correlations with instruments that evaluate different (although related) processes, namely, inhibition and processing speed. We conclude that the ucMOT possesses solid psychometric properties. Accordingly, we acquired normative data for the Portuguese population, which we present as a regression-based algorithm that yields z scores adjusted for age, gender, and years of formal education. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792506 TI - Testing the validity of criminal risk assessment tools in sexually abusive youth. AB - Although accurate risk appraisals are mandatory to provide effective treatment to juveniles who have sexually offended (JSOs), the current knowledge on the validity of risk assessment instruments for JSOs is inconclusive. We compared the predictive validities of the Juvenile Sex Offender Assessment Protocol II (J-SOAP II), the Estimate of Risk of Adolescent Sexual Offense Recidivism (ERASOR), and the Violence Risk Appraisal Guide-Revised (VRAG-R) scores concerning sexual, nonsexual-violent, and general criminal recidivism (based on both official and nonregistered reoffenses) in a consecutive sample of 597 male JSOs (Mage = 14.47 years, SDage = 1.57 years) while accounting for different recidivism periods, offense severities, and cumulative burden of adverse childhood experiences (ACEs). Receiver Operator Characteristic (ROC) curves and Cox regression analyses indicated that the tools allowed valid predictions of recidivism according to their intended purposes: The ERASOR was best suited to predict sexual recidivism within 0.5 and 3 years, the J-SOAP II was valid for predictions of sexual and nonsexual-violent recidivism within these recidivism periods, and the VRAG-R showed potential strengths in predicting nonsexual-violent recidivism, especially when committed above age 18. Elevated offense severity and burden of ACEs impeded predictive accuracies of the J-SOAP II and the VRAG-R, particularly in case of sexual recidivism. Our findings emphasize that risk assessment for JSOs must not rely solely on scores derived from risk assessment instruments, but a comprehensive consideration of a JSOs offense severity and psychosocial adversities is additionally necessary to approach accurate risk appraisals. (PsycINFO Database Record (c) 2018 APA, all rights reserved). PMID- 29792507 TI - Comparing self-report measures of grandiose narcissism, vulnerable narcissism, and narcissistic personality disorder in a male offender sample. AB - Despite a growing interest in the use of self-report measures of narcissism among student, community, and clinical samples, the research on narcissism in prison samples is sparse, despite elevated rates of narcissism in these samples. The current study examined the relations between commonly used measures of grandiose narcissism (Narcissistic Personality Inventory-13 [NPI-13]), vulnerable narcissism (Hypersensitive Narcissism Scale [HSNS]), and narcissistic personality disorder (NPD; Personality Diagnostic Questionnaire [PDQ]) in a sample of adult male offenders (N = 179). The NPI-13 and PDQ NPD scales overlapped substantially with one another and manifested similar empirical profiles (rICC = .81), with both being substantially correlated with interview-based symptoms of NPD, entitlement, psychopathy, and externalizing behaviors. Conversely, the HSNS manifested more limited relations with other measures of NPD and related traits (e.g., entitlement), as well as externalizing behaviors, and was more strongly related to internalizing symptoms. Consistent with previous work, NPD appears to be a blend of grandiose and vulnerable narcissism as the PDQ's empirical profile overlapped with that of the HSNS (rICC = .51), which was not true for the NPI-13 (rICC = .18). Analyses of the incremental validity of the 3 measures suggested that the NPI-13 was particularly successful in accounting for unique variance in these relevant criteria. These results underscore the benefit of utilizing multiple measures to distinguish empirical correlates of grandiose narcissism, vulnerable narcissism, and NPD. (PsycINFO Database Record PMID- 29792508 TI - Effects of TGF-beta Overexpression via rAAV Gene Transfer on the Early Repair Processes in an Osteochondral Defect Model in Minipigs. AB - BACKGROUND: Application of the chondrogenic transforming growth factor beta (TGF beta) is an attractive approach to enhance the intrinsic biological activities in damaged articular cartilage, especially when using direct gene transfer strategies based on the clinically relevant recombinant adeno-associated viral (rAAV) vectors. PURPOSE: To evaluate the ability of an rAAV-TGF-beta construct to modulate the early repair processes in sites of focal cartilage injury in minipigs in vivo relative to control (reporter lacZ gene) vector treatment. STUDY DESIGN: Controlled laboratory study. METHODS: Direct administration of the candidate rAAV-human TGF-beta (hTGF-beta) vector was performed in osteochondral defects created in the knee joint of adult minipigs for macroscopic, histological, immunohistochemical, histomorphometric, and micro-computed tomography analyses after 4 weeks relative to control (rAAV- lacZ) gene transfer. RESULTS: Successful overexpression of TGF-beta via rAAV at this time point and in the conditions applied here triggered the cellular and metabolic activities within the lesions relative to lacZ gene transfer but, at the same time, led to a noticeable production of type I and X collagen without further buildup on the subchondral bone. CONCLUSION: Gene therapy via direct, local rAAV-hTGF-beta injection stimulates the early reparative activities in focal cartilage lesions in vivo. CLINICAL RELEVANCE: Local delivery of therapeutic (TGF-beta) rAAV vectors in focal defects may provide new, off-the-shelf treatments for cartilage repair in patients in the near future. PMID- 29792509 TI - Modulation of Excitability in the Temporoparietal Junction Relieves Virtual Reality Sickness. AB - Virtual reality (VR) immersion often provokes subjective discomfort and postural instability, so called VR sickness. The neural mechanism of VR sickness is speculated to be related to visual-vestibular information mismatch and/or postural instability. However, the approaches proposed to relieve VR sickness through modulation of brain activity are poorly understood. Using transcranial direct current stimulation (tDCS), we aimed to investigate whether VR sickness could be relieved by the modulation of cortical excitability in the temporoparietal junction (TPJ), which is known to be involved in processing of both vestibular and visual information. Twenty healthy subjects received tDCS over right TPJ before VR immersion. The order of the three types of tDCS (anodal, cathodal, and sham) was counterbalanced across subjects. We evaluated the subjective symptoms, heart rate, and center of pressure at baseline, after tDCS, and after VR immersion. VR immersion using head-mounted displays provoked subjective discomfort and postural instability. However, anodal tDCS over right TPJ ameliorated subjective disorientation symptoms and postural instability induced by VR immersion compared with sham condition. The amelioration of VR sickness by anodal tDCS over the right TPJ might result from relief of the sensory conflict and/or facilitation of vestibular function. Our result not only has potential clinical implications for the neuromodulation approach of VR sickness but also implies a causal role of the TPJ in VR sickness. PMID- 29792510 TI - In reply to: "Intra-aortic balloon pump protects against hydrostatic pulmonary oedema during peripheral venoarterial-extracorporeal membrane oxygenation". AB - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized life-saving measure. However, left-ventricular distention from inadequate left-ventricular off-loading can lead to unwanted pulmonary and cardiac complications. We are writing to indicate our agreement with a recent article by Brechot et al. published in the June 2017 issue where the authors demonstrated that intra-aortic balloon pump provides mechanical support to off load the left ventricle during VA-ECMO, which prevents pulmonary edema. PMID- 29792511 TI - When a White Horse is a Horse: Embracing the (Obvious?) Overlap Between Acupuncture and Neuromodulation. PMID- 29792512 TI - Use of T2MR in invasive candidiasis with and without candidemia. AB - The mortality associated with invasive candidiasis remains unacceptably high. The T2 magnetic resonance (T2MR) assay is a novel US FDA-approved molecular diagnostic assay for the diagnosis of candidemia that can rapidly detect the five most commonly isolated Candida spp. In clinical trials, T2MR has exhibited good clinical sensitivity and specificity. Potential benefits from the adoption of T2MR technology in the diagnostic and therapeutic algorithms for invasive candidiasis can arise from timely diagnosis of disease, increased case detection, tailored therapy and decrease in empiric antifungal treatment. As everyday clinical experience with the assay is evolving, we discuss the utility of T2MR in invasive candidiasis with and without candidemia based on the currently available evidence regarding its performance. PMID- 29792513 TI - Cardiogenic shock complicating peripartum cardiomyopathy: Importance of early left ventricular unloading and bromocriptine therapy. AB - INTRODUCTION: Acute peripartum cardiomyopathy complicated by cardiogenic shock is a rare but life-threatening disease. A prolactin fragment is considered causal for the pathogenesis of peripartum cardiomyopathy. This analysis sought to investigate the role of early percutaneous mechanical circulatory support with micro-axial flow-pumps and/or veno-arterial extracorporeal membrane oxygenation in combination with the prolactin inhibitor bromocriptine in refractory cardiogenic shock complicating peripartum cardiomyopathy. METHODS AND RESULTS: In this single-centre analysis, five peripartum cardiomyopathy patients with refractory cardiogenic shock received mechanical circulatory support with either Impella CP microaxial pump only ( n=2) or in combination with veno-arterial extracorporeal membrane oxygenation ( n=3) in the setting of biventricular failure. All patients were mechanically ventilated. In all cases mechanical circulatory support was combined with bromocriptine therapy and early administration of levosimendan. All patients survived the acute phase of refractory cardiogenic shock. Mechanical circulatory support using a micro-axial pump allowed to significantly reduce catecholamine dosage. Remarkably, early left ventricular support with micro-axial flow-pumps resulted in myocardial recovery whereas delayed Impella (mechanical circulatory support) implantation was associated with poor left ventricular recovery. CONCLUSION: Mechanical circulatory support in patients with refractory cardiogenic shock complicating peripartum cardiomyopathy was associated with a 30-day survival of 100% and a favourable outcome. Notably, early left ventricular unloading combined with bromocriptine therapy was associated with left ventricular recovery. Therefore, an immediate transfer to a tertiary hospital experienced in mechanical circulatory support in combination with bromocriptine treatment seems indispensable for successful treatment of peripartum cardiomyopathy complicated by cardiogenic shock. PMID- 29792515 TI - Integrative Medicine: The Imperative for Health Justice in the Other Side of the World. PMID- 29792516 TI - Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective. AB - AIM: Estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. METHODS: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. RESULTS: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. CONCLUSION: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years. PMID- 29792514 TI - A Flow Procedure for Linearization of Genome Sequence Graphs. AB - Efforts to incorporate human genetic variation into the reference human genome have converged on the idea of a graph representation of genetic variation within a species, a genome sequence graph. A sequence graph represents a set of individual haploid reference genomes as paths in a single graph. When that set of reference genomes is sufficiently diverse, the sequence graph implicitly contains all frequent human genetic variations, including translocations, inversions, deletions, and insertions. In representing a set of genomes as a sequence graph, one encounters certain challenges. One of the most important is the problem of graph linearization, essential both for efficiency of storage and access, and for natural graph visualization and compatibility with other tools. The goal of graph linearization is to order nodes of the graph in such a way that operations such as access, traversal, and visualization are as efficient and effective as possible. A new algorithm for the linearization of sequence graphs, called the flow procedure (FP), is proposed in this article. Comparative experimental evaluation of the FP against other algorithms shows that it outperforms its rivals in the metrics most relevant to sequence graphs. PMID- 29792517 TI - Is phage therapy suitable for treating chronic sinusitis Staphylococcus aureus infection? PMID- 29792518 TI - It Is the Family Context That Matters: Concurrent and Predictive Effects of Aspects of Parent-Child Interaction on Video Gaming-Related Problems. AB - Studies have shown that children frequently experiencing poor parent-child interaction are prone to video gaming-related problems, but it is unclear which specific aspects of such an interaction play a predictive role in the problems. To extend previous research that relies primarily on the self-report method to assess parent-child interaction, we conducted a longitudinal, mixed-methods study. In a laboratory setting, three major aspects of interaction (i.e., affectivity, cohesiveness, and parental behavior) were observed in 241 parent child dyads (Children: 43 percent female, age range = 8-15, Mage = 12.09, SDage = 1.41; Parents: 78 percent female, age range = 27-63, Mage = 44.44, SDage = 6.09). In addition, both parent and children participants completed questionnaires that measured children's symptoms of Internet gaming disorder (IGD) and exposure to violent video games at baseline (Time 1) and 12 months later (Time 2). The results revealed that at Time 1, positive affectivity and cohesiveness were inversely associated with child-report symptoms of IGD. Also, Time 1 coerciveness (i.e., control dimension of parental behavior) was positively associated with Time 1 child-report exposure to violent video games and Time 2 child-report symptoms of IGD, respectively. Apart from main effects, the results also showed that Time 1 negative affectivity moderated the protective effects of Time 1 positive affectivity on Time 1 parent-report and Time 2 child-report exposure to violent video games, respectively. Overall, this study identifies various key aspects of parent-child interaction that may serve as concurrent or temporal predictors of video gaming-related issues. PMID- 29792519 TI - Effects of Online Physician Reviews and Physician Gender on Perceptions of Physician Skills and Primary Care Physician (PCP) Selection. AB - Physician review websites have become more relevant and important in people's selection of physicians. The current study experimentally examined how online physician reviews endorsing a primary care physician's (PCP's) technical or interpersonal skills, along with a physician's gender, may influence people's perceptions of the physician's skills and their willingness to choose the physician. Participants were randomly assigned to view a mockup physician review web page and to imagine that they needed to find a new PCP in a new city. They were then asked to report their perceptions of the physician and willingness to choose the physician as their PCP. The results suggested that people's willingness to choose a PCP was affected by physician reviews through their influence on people's perceptions of the PCP's technical and interpersonal skills. More importantly, this study found that when physician reviews endorsed a PCP's technical skills people perceived a female PCP to be more interpersonally competent than a male PCP and thus were more likely to choose the female PCP. The gendered perception, however, was not extended to a PCP's technical skills. Practical implications for health providers and consumers are discussed. PMID- 29792520 TI - Changes in the Neurovascular Anatomy of the Shoulder After an Open Latarjet Procedure: Defining a Surgical Safe Zone. AB - BACKGROUND: Although previous literature has described the relevant anatomy for an open anterior Bankart approach of the shoulder, there is little known regarding the anatomic relationship changes in the neurovascular structures after an open Latarjet procedure. PURPOSE: To define the neurovascular anatomy of the native shoulder in relation to the coracoid and to define the anatomy after the Latarjet procedure in relation to the glenoid to determine distances to these neurovascular structures with and without neurolysis of the musculocutaneous nerve (MCN) from the conjoint tendon. STUDY DESIGN: Descriptive laboratory study. METHODS: Fourteen fresh-frozen male cadaveric shoulders (7 matched pairs) were utilized. The distances of 7 neurovascular structures (the main trunk of the MCN at its insertion into the conjoint tendon, the MCN at its closest location to the coracoid process, the lateral cord of the plexus, the split of the lateral cord and MCN, the posterior cord of the plexus, the axillary nerve, and the axillary artery) to pertinent landmarks were first measured in the native state in relation to the coracoid. After the Latarjet procedure, these landmarks were measured in relation to the glenoid. In addition, measurements of the MCN distances were performed both with and without neurolysis of the MCN from the conjoint tendon. All measurements were performed using digital calipers and reported as medians with ranges. RESULTS: The median MCN entry into the conjoint tendon was 56.5 mm (range, 43.0-82.2 mm) and 57.1 mm (range, 23.5-92.9 mm) from the tip of the coracoid in the neurolysis group and nonneurolysis group, respectively ( P = .32). After the Latarjet procedure, the median MCN entry into the conjoint tendon was 43.8 mm (range, 20.2-58.3 mm) and 35.6 mm (range, 27.3 84.5 mm) from the 3-o'clock position of the glenoid in the neurolysis and nonneurolysis groups, respectively ( P = .83). The median MCN entry into the conjoint tendon was 35.6 mm (range, 25.1-58.0 mm) and 36.3 mm (range, 24.4-77.9 mm) from the 6-o'clock position in the neurolysis group and nonneurolysis group, respectively ( P = .99). After the Latarjet procedure, the closest neurovascular structures in relation to both the 3-o'clock and 6-o'clock positions to the coracoid were the axillary nerve at a median 27.4 mm (range, 19.8-40.0 mm) and 27.7 mm (range, 23.2-36.1 mm), respectively. CONCLUSION: This study identified a minimum distance medial to the glenoid after the Latarjet procedure to be approximately 19.8 mm for the axillary nerve, 23.6 mm for the posterior cord, and 24.4 mm and 20.2 mm for the MCN without and with neurolysis, respectively. Neurolysis of the MCN did not significantly change the distance of the nerve from pertinent landmarks compared with no neurolysis, and routine neurolysis may not be indicated. However, the authors still advise that there may be clinical benefit to performing neurolysis during surgery, especially given that the short length of the MCN puts it at risk for traction injuries during the Latarjet procedure. CLINICAL RELEVANCE: The findings of this study provide an improved understanding of the position of the neurovascular structures after the Latarjet procedure. Knowledge of these minimum distances will help avoid iatrogenic damage of the neurovascular structures when performing procedures involving transfer of the coracoid process. PMID- 29792521 TI - Problematic Video Gaming in a Young Spanish Population: Association with Psychosocial Health. AB - Problematic video gaming (PVG) is a concern for psychologists attending children and adolescents. Uniform diagnostic criteria are lacking, and risk factors are poorly understood. Internet gaming disorder (IGD) was included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and scales derived from its diagnostic criteria may be helpful to assess PVG. A multicenter study was conducted in secondary schools using an IGD-derived scale (dichotomous Nine-Item Internet Gaming Disorder Scale [IGD-9]), analyzing PVG-related variables. Seven hundred eight students (55.8 percent male) with mean age 15.6 +/ 2.7 years were included. Seventy-three percent were gamers and 22 percent heavy gamers (HGs). Forty-five percent reported online gaming and 6.6 percent massive multiplayer online role-playing games (MMORPGs). Fifty-nine students (8.3 percent) scored 5 or more in IGD-9 and were classified as IGD+. HG and IGD+ subjects were more frequently male and online and MMORPG gamers (p < 0.01). However, IGD+ subjects had significantly worse psychosocial scores than IGD- (p < 0.001), while HGs did not significantly differ from casual gamers (p > 0.01). The multivariate analysis showed that IGD+ scores were significantly associated with worse psychosocial health and adjustment (p < 0.001), while the other variables (male sex, online and MMORPG gaming, and HG) were not significantly associated (p > 0.01). The IGD-9 scale scored positive in 8.3 percent of our sample. Unlike gaming time, this scale was associated with psychosocial disturbances, making it potentially useful as a screening method to detect candidates for clinical intervention. PMID- 29792522 TI - Love, Sex, and Personality Pathology: A Life History View of Personality Pathologies and Sociosexuality. AB - Love and sex are fundamental needs of most people, yet little research has examined such aspects of life in relation to personality pathologies. We examined the associations between pathological personality traits (i.e., negative affectivity, disinhibition, antagonism, psychoticism, and detachment) and sociosexuality (i.e., short-term mating orientation, long-term mating orientation, and sexual behavior) among 702 university students. In addition, we examined the mediating role of life history speed and tested whether sex moderated the associations that these pathological personality traits had with sociosexuality. Detachment, antagonism, disinhibition, and psychoticism had positive associations with short-term mating interests and negative associations with long-term mating interests. Life history speed mediated the associations that detachment and disinhibition had with short-term mating orientation and long term mating orientation. Although sex did moderate the association that negative affectivity had with previous sexual behavior, we found no evidence that these mediational processes differed between men and women. Results are discussed in terms of the way personality traits shape the sociosexuality of men and women using a life history paradigm. PMID- 29792523 TI - Personality Homophily and Geographic Distance in Facebook. AB - Personality homophily remains an understudied aspect of social networks, with the traditional focus concerning sociodemographic variables as the basis for assortativity, rather than psychological dispositions. We consider the effect of personality homophily on one of the biggest constraints to human social networks: geographic distance. We use the Big Five model of personality to make predictions for each of the five facets: Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism. Using a network of 313,669 Facebook users, we investigate the difference in geographic distance between homophilous pairs, in which both users scored similarly on a particular facet, and mixed pairs. In accordance with our hypotheses, we find that pairs of open and conscientious users are geographically further apart than mixed pairs. Pairs of extraverts, on the other hand, tend to be geographically closer together. We find mixed results for the Neuroticism facet, and no significant effects for the Agreeableness facet. The results are discussed in the context of personality homophily and the impact of geographic distance on social connections. PMID- 29792525 TI - Modelling category goodness judgments in children with residual sound errors. AB - This study investigates category goodness judgments of /r/ in adults and children with and without residual speech errors (RSEs) using natural speech stimuli. Thirty adults, 38 children with RSE (ages 7-16) and 35 age-matched typically developing (TD) children provided category goodness judgments on whole words, recorded from 27 child speakers, with /r/ in various phonetic environments. The salient acoustic property of /r/ - the lowered third formant (F3) - was normalized in two ways. A logistic mixed-effect model quantified the relationships between listeners' responses and the third formant frequency, vowel context and clinical group status. Goodness judgments from the adult group showed a statistically significant interaction with the F3 parameter when compared to both child groups (p < 0.001) using both normalization methods. The RSE group did not differ significantly from the TD group in judgments of /r/. All listeners were significantly more likely to judge /r/ as correct in a front-vowel context. Our results suggest that normalized /r/ F3 is a statistically significant predictor of category goodness judgments for both adults and children, but children do not appear to make adult-like judgments. Category goodness judgments do not have a clear relationship with /r/ production abilities in children with RSE. These findings may have implications for clinical activities that include category goodness judgments in natural speech, especially for recorded productions. PMID- 29792524 TI - Managing comorbid cardiovascular disease and sleep apnea with pharmacotherapy. AB - INTRODUCTION: Highly prevalent sleep disordered breathing (SDB) has been recognized as an independent cardiovascular disease (CVD) risk factor. Although these two entities often coexist, there is a shortage of sufficiently-powered studies testing the interplay between the course of sleep apnea and CVD pharmacotherapy. The mutual relationship between treated/untreated obstructive sleep apnea (OSA) with ongoing cardiovascular pharmacotherapies is an evident gap in clinical expertise. Areas covered: In this article, the authors review the available evidence and outline future research directions concerning the reciprocal relationship between the pharmacological treatment of CVD and SDB. Several attempts have been made to identify the most efficacious hypotensive agents for patients with both OSA and hypertension. Various cardiovascular drugs are also evaluated in terms of their influence on sleep apnea severity. Expert opinion: The question of whether OSA should be included in cardiovascular pharmacotherapy individualization algorithms is a matter of debate and more evidence is needed. Cautious intensification of diuretics with the use of aldosterone receptor antagonists deserves attention when both high blood pressure and sleep apnea coexist. PMID- 29792526 TI - Phages & antibiotic resistance: are the most abundant entities on earth ready for a comeback? AB - Bacteriophages, which lost out to antibiotic therapy in the past, may be poised to make a comeback. Once discarded because of their narrow activity spectrum, it can now be viewed as a major advantage that these intracellular, self-replicating entities can exert their killing effect with minimal damage to the commensal microbiome. In eastern Europe, phages continue to be used both prophylactically and therapeutically to treat infections. More recently, much needed regulated clinical trials are underway with a view to restoring phage therapy as a tool for mainstream medicine, although current regulations may impede their full potential. One hundred years after their discovery, and amid an antibiotic resistance crisis, we must ask, what can be done to harness their full antibacterial potential? PMID- 29792528 TI - Dissociation of cerebrospinal fluid amyloid-beta and tau levels in patients with prolonged posttraumatic disorders of consciousness. AB - BACKGROUND: Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease (AD). Although the mechanisms that lead to AD after a TBI are unclear, we hypothesize that changes in amyloid-beta (Abeta) metabolism and abnormal tau phosphorylation are reasonable candidates. OBJECTIVE: To investigate Abeta and tau dynamics in the chronic phase of TBI. METHODS: We evaluated Abeta1-42, total tau (t-tau), and phosphorylated tau (p-tau) levels in the cerebrospinal fluid (CSF) of 15 patients who developed a prolonged disorder of consciousness after a severe TBI (mean time from TBI 271.6 +/- 176.5 days). RESULTS: Reduced Abeta1-42 levels (median 258 pg/ml, range 90-833.6) were observed in 14/15 patients (93.3%) with severe post-TBI disorders of consciousness. These CSF analysis data did not correlate with time since TBI or with the patients' level of consciousness as determined by the Coma Recovery Scale Revised. Normal t-tau levels (median 95.2 pg/ml, range 52-256.9) were found in all patients. Normal p-tau levels (median 22.2 pg/ml, range 14-72) were observed in 14/15 patients, with just a single patient having a slightly increased p-tau level. CONCLUSION: The present findings show that Abeta and tau are differently affected in the chronic phase of severe TBI. PMID- 29792527 TI - Enteric Neural Stem Cells Expressing Insulin-Like Growth Factor 1: A Novel Cellular Therapy for Hirschsprung's Disease in Mouse Model. AB - Transplanting enteric neural stem cells (ENSCs) is an innovative approach for replacing enteric neurons in Hirschsprung's disease (HSCR). However, posttransplantation cell survival and differentiation limit efficacy. We aimed to investigate whether transplantation of ENSCs engineered with insulin-like growth factor 1 (IGF-1) could improve survival and differentiation of the engrafted cells and promote functional recovery of the aganglionic colon. ENSCs were isolated from the intestine of neonatal mice and genetically modified to express IGF-1. After implantation into the mice aganglionic colon induced by benzalkonium chloride, survival and differentiation of engrafted cells were assessed by immunohistochemistry for GFP, neuronal, and glial cell markers. Colonic motility was quantified by colonic bead expulsion time and response to electrical field stimulation (EFS). Expression of the neural marker nNOS and the glial cell marker (glial fibrillary acidic protein [GFAP]) was increased in IGF-1-ENSCs. IGF-1 had also improved neuroglial differentiation of ENSCs following transplantation in vivo. Colonic motility was significantly improved after IGF-1-ENSC transplantation, as demonstrated by reduction of colonic bead expulsion time and recovery of EFS-induced relaxation. IGF-1 has enhanced neurogenesis and function of ENSCs upon transplantation for enteric nervous system replacement, which may provide a potential novel therapy for the treatment of HSCR. PMID- 29792529 TI - miR-155 accelerates proliferation of mouse hepatocytes during liver regeneration by directly targeting SOCS1. AB - Liver regeneration after two-thirds partial hepatectomy (PH) is a clinically significant repair process for restoring proper liver architecture. Although microRNA-155 (miR-155) has been found to serve as a crucial microRNA regulator that controls liver cell function and proliferation, little is known about its specific role in the regenerating liver. Using a mouse model with miR-155 overexpression or miR-155 knockout, we investigated the molecular mechanisms of miR-155 in liver regeneration. We found a marked induction of miR-155 in C57BL/6 mice after PH. Furthermore, RL-m155 mice showed enhanced liver regeneration as a result of accelerated progression of hepatocytes into the cell cycle, mainly through an increase in cyclin levels. However, proliferation of hepatocytes was delayed in miR-155-deficient livers. Expression of suppressor of cytokine signaling 1 (SOCS1) was dramatically downregulated in the process of liver regeneration, and enhancement of SOCS1 contributed to impaired proliferation of hepatocytes. Additionally, in vitro and in vivo experiments showed that adenovirus- or adeno-associated virus-mediated overexpression of SOCS1 attenuated improved liver regeneration induced by miR-155 overexpression. Our study shows that miR-155 is a pro-proliferative regulator in liver regeneration by facilitating the cell cycle and directly targeting SOCS1. NEW & NOTEWORTHY Our findings suggest a microRNA-155 (miR-155)-mediated positive regulation pattern in liver regeneration. A series of in vivo and in vitro studies showed that miR-155 upregulation enhanced partial hepatectomy-induced proliferation of hepatocytes by promoting the cell cycle without inducing DNA damage or apoptosis. Suppressor of cytokine signaling 1, a target gene of miR-155, antagonized the proliferation promoting effect of miR-155. Therefore, pharmacological intervention targeting miR-155 may be therapeutically beneficial in various liver diseases. PMID- 29792530 TI - Manganese transport and toxicity in polarized WIF-B hepatocytes. AB - Manganese (Mn) toxicity arises from nutritional problems, community and occupational exposures, and genetic risks. Mn blood levels are controlled by hepatobiliary clearance. The goals of this study were to determine the cellular distribution of Mn transporters in polarized hepatocytes, to establish an in vitro assay for hepatocyte Mn efflux, and to examine possible roles the Mn transporters would play in metal import and export. For these experiments, hepatocytoma WIF-B cells were grown for 12-14 days to achieve maximal polarity. Immunoblots showed that Mn transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14 were present. Indirect immunofluorescence microscopy localized Fpn and ZIP14 to WIF-B cell basolateral domains whereas ZnT10 and ZIP8 associated with intracellular vesicular compartments. ZIP8-positive structures were distributed uniformly throughout the cytoplasm, but ZnT10-positive vesicles were adjacent to apical bile compartments. WIF-B cells were sensitive to Mn toxicity, showing decreased viability after 16 h exposure to >250 MUM MnCl2. However, the hepatocytes were resistant to 4-h exposures of up to 500 MUM MnCl2 despite 50 fold increased Mn content. Washout experiments showed time-dependent efflux with 80% Mn released after a 4 h chase period. Hepcidin reduced levels of Fpn in WIF-B cells, clearing Fpn from the cell surface, but Mn efflux was unaffected. The secretory inhibitor, brefeldin A, did block release of Mn from WIF-B cells, suggesting vesicle fusion may be involved in export. These results point to a possible role of ZnT10 to import Mn into vesicles that subsequently fuse with the apical membrane and empty their contents into bile. NEW & NOTEWORTHY Polarized WIF-B hepatocytes express manganese (Mn) transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14. Fpn and ZIP14 localize to basolateral domains. ZnT10-positive vesicles were adjacent to apical bile compartments, and ZIP8-positive vesicles were distributed uniformly throughout the cytoplasm. WIF-B hepatocyte Mn export was resistant to hepcidin but inhibited by brefeldin A, pointing to an efflux mechanism involving ZnT10-mediated uptake of Mn into vesicles that subsequently fuse with and empty their contents across the apical bile canalicular membrane. PMID- 29792532 TI - The Moderating Influence of Disorder on Coached Overreporting Using the MMPI-2 RF. AB - Overreporting has always been a concern within psychological evaluations. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (Ben-Porath & Tellegen, 2008/2011 ) contains validity scales designed for detecting noncredible responses. In this study, 270 undergraduates were instructed to feign either schizophrenia, posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD); some participants were coached on symptoms and validity scales. Results at both the individual protocol and mean validity scale score levels suggest that each feigned disorder moderates the effectiveness of coaching on validity scale detection. One finding of this study suggests that schizophrenia is generally more difficult to successfully feign than PTSD or GAD. Another finding suggests that the majority of individuals able to avoid detection as symptom overreporters are able to successfully endorse at least some disorder relevant symptoms. We suggest that future research focus on the systematic exploration of other factors influencing the effectiveness of validity scales as well as the development of validity scales designed to detect the overreporting of internalizing forms of psychopathology. PMID- 29792531 TI - Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal Na+/H+ exchanger 3 by lysophosphatidic acid in vivo. AB - Lysophosphatidic acid (LPA) is a bioactive lipid molecule, which regulates a broad range of pathophysiological processes. Recent studies have demonstrated that LPA modulates electrolyte flux in the intestine, and its potential as an antidiarrheal agent has been suggested. Of six LPA receptors, LPA5 is highly expressed in the intestine. Recent studies by our group have demonstrated activation of Na+/H+ exchanger 3 (NHE3) by LPA5. However, much of what has been elucidated was achieved using colonic cell lines that were transfected to express LPA5. In the current study, we engineered a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5DeltaIEC, and investigated the role of LPA5 in NHE3 regulation and fluid absorption in vivo. The intestine of Lpar5DeltaIEC mice appeared morphologically normal, and the stool frequency and fecal water content were unchanged compared with wild-type mice. Basal rates of NHE3 activity and fluid absorption and total NHE3 expression were not changed in Lpar5DeltaIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5DeltaIEC mice, providing direct evidence for the regulatory role of LPA5. NHE3 activation involves trafficking of NHE3 from the terminal web to microvilli, and this mobilization of NHE3 by LPA was abolished in Lpar5DeltaIEC mice. Dysregulation of NHE3 was specific to LPA, and insulin and cholera toxin were able to stimulate and inhibit NHE3, respectively, in both wild-type and Lpar5DeltaIEC mice. The current study for the first time demonstrates the necessity of LPA5 in LPA-mediated stimulation of NHE3 in vivo. NEW & NOTEWORTHY This study is the first to assess the role of LPA5 in NHE3 regulation and fluid absorption in vivo using a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5DeltaIEC. Basal rates of NHE3 activity and fluid absorption, and total NHE3 expression were not changed in Lpar5DeltaIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5DeltaIEC mice, providing direct evidence for the regulatory role of LPA5. PMID- 29792533 TI - Efficacy of the resilience and adjustment intervention after traumatic brain injury: a randomized controlled trial. AB - OBJECTIVE: Examine a psychoeducational and skill-building intervention's effectiveness for individuals after traumatic brain injury (TBI), using a two arm, parallel, randomized, controlled trial with wait-listed control. METHODS: The Resilience and Adjustment Intervention (RAI) targets adjustment challenges and emphasizes education, skill-building and psychological support. Overall, 160 outpatients were randomly assigned to a treatment or wait-list control (WLC) group. The manualized treatment was delivered in seven 1-h sessions. The Connor Davidson Resilience Scale (CD-RISC) was the primary outcome measure. Secondary measures included the Mayo Portland Adaptability Inventory-4 (MPAI-4), Brief Symptom Inventory-18 (BSI-18) and 13-Item Stress Test. RESULTS: After adjusting for injury severity, education and time postinjury, the RAI group (N = 75) demonstrated a significantly greater increase in resilience (effect size = 1.03) compared to the WLC group (N = 73). Participants in the RAI group demonstrated more favourable scores on the MPAI-4 Adjustment and Ability Indices, BSI-18 and the 13-item Stress Test. However, only the CD-RISC and BSI-18 demonstrated a clinically significant difference. In addition, RAI participants demonstrated maintenance of gains from pre-treatment to 3-month follow-up; however, only the BSI-18 maintained a clinically significant difference. CONCLUSIONS: Investigation provided evidence that a resilience-focused intervention can improve psychological health and adjustment after TBI. Additional research is needed to ascertain the longer term benefits of intervention and the efficacy of alternative delivery methods (e.g., via telephone, Internet). PMID- 29792534 TI - Intensity of previous teaching but not diagnostic skills influences stigmatization of patients with substance use disorder by general practice residents. A vignette study among French final-year residents in general practice. AB - BACKGROUND: High levels of stigma towards patients with substance use disorder (SUD) have been found in health professionals and medical students. OBJECTIVES: To assess the capability of residents in general practice to diagnose SUD correctly; to assess their stigmatization of patients with SUD and to assess the correlation between both variables. We hypothesized a negative correlation. METHODS: In 2014, we conducted a cross-sectional survey among French residents in general practice, using a self-administered questionnaire. First, a clinical case of SUD (tramadol) was presented, to assess the diagnosis and retained diagnostic criteria. A second clinical vignette was presented (intravenous heroin user) to assess stigmatization with the Attitudes to Mental Illness Questionnaire (AMIQ). Its score ranges from -10 (negative attitude) to +10 (positive attitude). AMIQ scores of residents who diagnosed SUD correctly versus incorrectly, and who had received at least six hours versus less than six hours of teaching on this topic, were compared using Student's t-test. RESULTS: Of 1284 solicited residents, 303 participated (23.6%), 249 residents diagnosed SUD correctly (82.2%). The mean AMIQ score was -3.91 (SD 2.4) without significant difference regarding the correct diagnosis of SUD; but with a significant difference between residents who had received training in SUD for at least six hours versus residents less trained (AMIQ scores -3.76 (SD 2.46) versus -4.50 (SD 2.27), p = .0354). CONCLUSION: Residents in general practice had a good capacity to diagnose SUD correctly but on average expressed negative attitudes toward people with SUD. More SUD teaching seems to help in reducing stigmatizing attitudes. PMID- 29792536 TI - Outcomes in paediatric external dacryocystorhinostomy: a single-centre experience. AB - PURPOSE: To report the outcomes of external dacryocystorhinostomy (Ext DCR) in paediatric patients. METHODS: A single-centre, retrospective, interventional, non comparative case series was performed on all paediatric patients who underwent Ext DCR between July 2010 and July 2014. Surgery was performed as per standard Ext DCR protocols with only anterior flap suturing. Data collected include demographics, clinical presentations, primary diagnosis, associated systemic anomalies, past interventions, indications for the surgery, use of adjuvants, intraoperative and post-operative complications, aetiology of DCR failure, anatomical and functional successes. RESULTS: 135 eyes of 114 children underwent Ext DCR during the study period. Mean age was 9.68 +/- 4.36 years and epiphora was the most common presentation (92.5%, 125/135). Persistent congenital nasolacrimal duct obstruction refractory to earlier interventions of probing or intubation was the most common indication for the surgery noted in 57% (77/135). Adjuvants like mitomycin C and intubation were used in 70% (95/135) and 72% (98/135) of the surgeries, respectively. At a 6-month follow-up, anatomical and functional successes were noted in 91.1% (124/135) and 90.3% (123/135), respectively. 12 eyes showed anatomical failure and one eye showed functional failure. The most common cause of DCR failure was a complete cicatricial closure of the ostium (83.4%, 10/12). CONCLUSIONS: This study shows that Ext DCR is a safe surgery for paediatric populations with a high success rates of beyond 90%. PMID- 29792535 TI - Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients. AB - BACKGROUND: More than 80% of patients with advanced cancer develop weight loss. Because preclinical data suggest poly (ADP-ribose) polymerase (PARP) inhibitors can treat this weight loss, this study was undertaken to explore the PARP inhibitor veliparib for this indication. OBJECTIVE: The current study was undertaken to analyze prospectively gathered data on weight in cancer patients on PARP inhibitors. DESIGN/SETTING: The current study relied on a previously published, prospectively conducted phase 1 single institution trial that combined veliparib and topotecan (NCT01012817) as antineoplastic therapy for advanced cancer patients. Serial weight data and, when available and clinically relevant, computerized tomography scans were also examined. MEASUREMENTS: The primary endpoint was 10% or greater weight gain from trial enrollment. RESULTS: Nearly all 60 patients lost weight over time. Only one patient manifested a 10% or greater gain in weight. However, review of computerized tomography L3 images showed this weight gain was a manifestation of ascites. Four other patients gained 5% of their baseline weight. However, findings in two patients with available radiographs showed no evidence of muscle augmentation. CONCLUSIONS: The addition of the PARP inhibitor veliparib to chemotherapy does not appear to result in notable weight gain or in weight maintenance in patients with advanced cancer. Interventions other than PARP inhibitors should be considered for the palliation/treatment of cancer-associated weight loss. PMID- 29792537 TI - Recognizing, quantifying and managing patient-ventilator asynchrony in invasive and noninvasive ventilation. AB - INTRODUCTION: Patient-ventilator asynchrony may occur with modes of partial ventilatory support. Because this problem is associated with worsened outcomes, identifying and managing asynchronies has been recognized as a relevant clinical problem during both invasive and noninvasive (NIV) mechanical ventilation. Areas covered: In this review article, we first describe the different forms of patient ventilator asynchrony and how they are classified and quantified. Then, we show how these asynchronies can be recognized, considering the techniques used to properly detect asynchronies, by either ventilator waveform observation, or through systems based on more complexes mathematical algorithms, by means of adjunctive signals, such as the electrical activity of the diaphragm or esophageal pressure. Finally, we describe the actions that can be undertaken in order to limit the rate of asynchronies during both invasive ventilation and NIV mechanical ventilation, such as modifications of the ventilator mode and/or settings, variation of the sedation regimen (type and doses), and other technical pitfalls. Expert commentary: Detection of asynchronies is crucial in order to reduce their incidence, adopting adjustments of the ventilator settings, sedation regimen, and other technical pitfalls. It remains to be clarified whether the relationship between high incidence of asynchrony and worsened outcome is causative or just associative. PMID- 29792538 TI - Single-Nucleotide Polymorphisms in IL23R-IL12RB2 (rs1495965) Are Highly Prevalent in Patients with Behcet's Uveitis, and Vary between Populations. AB - PURPOSE: To test the frequency of single-nucleotide polymorphisms in the IL-10, IL23R-IL12RB2 genes in patients with Behcet's uveitis. METHODS: Blood samples were collected from 89 Israeli and Turkish patients, and from healthy control subjects of different origins. Genomic DNA was extracted from peripheral blood leukocytes and genotyped. RESULTS: The risk allele, A, in rs1800871, of IL-10 gene was highly prevalent in Behcet's uveitis and healthy control samples alike; highest among the Turkish groups. Prevalence of G allele, in rs1495965, in the IL23R-IL12RB2 gene was high in Behcet's uveitis patients, and among healthy Turkish and Israelis of Middle Eastern origin, while lower among the other Israeli control group (77.9%, 78.9%, 27.8%, respectively, P < 0.001). CONCLUSION: Our findings highlight the differences between populations and may account for the increased prevalence of the disease among Turkish and Israelis of Middle Eastern origin. Further studies are required to map other healthy and affected populations. PMID- 29792539 TI - Why anthropology should be a compulsory component in medical training. PMID- 29792540 TI - Cerebral amyloid angiopathy: diagnosis and potential therapies. AB - INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the pathologic deposition of amyloid-beta within cortical and leptomeningeal arteries, arterioles, capillaries and, in rare cases, the venules of the brain. It is often associated with the development of lobar intracerebral hemorrhages (ICHs) but may cause other neurologic symptoms or be asymptomatic. Magnetic resonance imaging characteristics, such as lobar microbleeds, support a diagnosis of CAA and assist with hemorrhage risk assessments. Immunosuppressants are used to treat rarer inflammatory forms of CAA. For the more common forms of CAA, the use of antihypertensive medications can prevent ICH recurrence while the use of antithrombotics may increase hemorrhage risk. Anti-amyloid approaches to treatment have not yet been investigated in phase 3 trials. Areas covered: A literature search was conducted using MEDLINE on the topics of imaging, biomarkers, ICH prevention and treatment trials in CAA, focusing on its current diagnosis and management and opportunities for future therapeutic approaches. Expert commentary: There is likely a significant unrecognized burden of CAA in the elderly population. Continued research efforts to discover biomarkers that allow the early diagnosis of CAA will enhance the opportunity to develop treatment interventions. PMID- 29792541 TI - Interaction of low frequency external electric fields and pancreatic beta-cell: a mathematical modeling approach to identify the influence of excitation parameters. AB - PURPOSE: Although the effect of electromagnetic fields on biological systems has attracted attraction in recent years, there has not been any conclusive result concerning the effects of interaction and the underlying mechanisms involved. Besides the complexity of biological systems, the parameters of the applied electromagnetic field have not been estimated in most of the experiments. MATERIALS AND METHODS: In this study, we have used computational approach in order to find the excitation parameters of an external electric field which produces sensible effects in the function of insulin secretory machinery, whose failure triggers the diabetes disease. A mathematical model of the human beta cell has been used and the effects of external electric fields with different amplitudes, frequencies and wave shapes have been studied. RESULTS: The results from our simulations show that the external electric field can influence the membrane electrical activity and perhaps the insulin secretion when its amplitude exceeds a threshold value. Furthermore, our simulations reveal that different waveforms have distinct effects on the beta-cell membrane electrical activity and the characteristic features of the excitation like frequency would change the interaction mechanism. CONCLUSION: The results could help the researchers to investigate the possible role of the environmental electromagnetic fields on the promotion of diabetes disease. PMID- 29792543 TI - Restructuring Saudi Board in Restorative Dentistry (SBRD) curriculum using CanMEDS competency. AB - OBJECTIVE: The purpose of this paper is to describe the process of adopting the Canadian Medical Education Directions for Specialists (CanMEDS) 2015 competency framework in a dental specialty program to reconstruct the Saudi Board in Restorative Dentistry (SBRD) curriculum and disseminate the lessons learned. Method and development process: The process of curriculum development was started with the selection of SBRD curriculum committee and review of CanMEDS framework. The Committee conducted needs assessment among the stakeholders and adopted CanMEDS 2015 competencies through a careful process. A modeled curriculum was developed after taking feedback, review of existing literature, and unique context of dentistry. Curriculum: Several unique features are incorporated. For example, milestones and continuum of learning are developed to enable residents develop competencies at different stages (transition to discipline, foundation of discipline, and core of discipline). Academic activities are restructured to encourage interactive, student-centered approaches, team work, intellectual curiosity, and scholarship. Learning outcomes are integrated throughout within several modules. Many formative assessment tools are adopted to promote learning and evaluate clinical skills. CONCLUSIONS: This is the first published example of adopting CanMEDS competency framework in a dental specialty program. The success of developing SBRD curriculum has encouraged other dental specialties toward adopting CanMEDS 2015 frameworks for their own curricula. PMID- 29792545 TI - An update on quality control for the PFA-100/PFA-200. AB - Testing of platelet function comprises a crucial element of hemostasis assessment, particularly for investigations into bleeding and/or bruising. The Platelet Function Analyzer (PFA)-100 is the most utilized primary hemostasis screening test system available, as recently remodeled/upgraded to the PFA-200. Internal quality control (IQC) and external quality assessment (EQA) (including proficiency testing) represent critical elements of ensuring test practice quality. Although true for all tests, IQC and EQA are logistically challenging for platelet function testing, inclusive of the PFA-100/200. We accordingly update our experience with novel yet feasible approaches to both IQC and EQA of PFA-100/200. Over the past 10 years, a total of 43 challenges have been tested, with most challenges designed to mimic moderate or severe primary hemostasis defects. The current report is restricted to the last four years and has also differentially assessed PFA-100 vs. PFA-200 EQA results to identify potential variance. Numerical results for closure times (CTs) and participant-supplied interpretive comments were analyzed. Reported CTs for each challenge were within limits of expectation, and good reproducibility was evidenced by repeated challenges. Coefficients of variation (CVs) for challenges, generally ranging from 15% to 25%, were similar or better than those obtained using native whole blood and consistent with past reports. Participant interpretations were generally consistent with test data and expectations. There was no evident difference in PFA-100 vs. PFA-200 EQA test results. The EQA material has also been successfully evaluated from the perspective of potential IQC. To conclude, IQC and EQA processes for the PFA-100/200 have been established that are highly reproducible, supporting the concept of EQA/IQC for platelet function testing, and also facilitating monitoring and improvement in its performance. In terms of EQA, PFA-100 and PFA-200 instruments appear to behave similarly. PMID- 29792542 TI - A Novel Research Definition of Bladder Health in Women and Girls: Implications for Research and Public Health Promotion. AB - BACKGROUND: Bladder health in women and girls is poorly understood, in part, due to absence of a definition for clinical or research purposes. This article describes the process used by a National Institutes of Health funded transdisciplinary research team (The Prevention of Lower Urinary Tract Symptoms [PLUS] Consortium) to develop a definition of bladder health. METHODS: The PLUS Consortium identified currently accepted lower urinary tract symptoms (LUTS) and outlined elements of storage and emptying functions of the bladder. Consistent with the World Health Organization's definition of health, PLUS concluded that absence of LUTS was insufficient and emphasizes the bladder's ability to adapt to short-term physical, psychosocial, and environmental challenges for the final definition. Definitions for subjective experiences and objective measures of bladder dysfunction and health were drafted. An additional bioregulatory function to protect against infection, neoplasia, chemical, or biologic threats was proposed. RESULTS: PLUS proposes that bladder health be defined as: "A complete state of physical, mental, and social well-being related to bladder function and not merely the absence of LUTS. Healthy bladder function permits daily activities, adapts to short-term physical or environmental stressors, and allows optimal well-being (e.g., travel, exercise, social, occupational, or other activities)." Definitions for each element of bladder function are reported with suggested subjective and objective measures. CONCLUSIONS: PLUS used a comprehensive transdisciplinary process to develop a bladder health definition. This will inform instrument development for evaluation of bladder health promotion and prevention of LUTS in research and public health initiatives. PMID- 29792544 TI - Synergistic Phytochemicals Fail to Protect Against Ovariectomy Induced Bone Loss in Rats. AB - Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks. Retired-breeder, Fischer 344 rats were randomly assigned to sham or ovariectomy surgery and 4 treatment groups: ZA; genistein supplementation; and a low dose and high dose blend of genistein, resveratrol, and quercetin. Ovariectomy resulted in a loss of both trabecular and cortical bone which was prevented with ZA. The phytochemical blends tested were unable to reverse these losses. Despite the lack of effectiveness in preventing bone loss, a significant dose-response trend was observed in the phytochemical-rich diets in bone adipocyte number compared to ovariectomized control rats. Data from this study indicate that estrogenic phytochemicals are not as efficacious as ZA in preventing menopausal-related bone loss but may have beneficial effects on bone marrow adiposity in rats. PMID- 29792546 TI - Application of a mixture model to assess the effect of measles-mumps-rubella vaccine on the mumps epidemic in children from kindergarten to early school age in Jiangsu Province, China. AB - A single dose of the measles-mumps-rubella (MMR) vaccine has been applied in routine immunizations for children in China; however, the Immunoglobulin G (IgG) antibody level of mumps in children from kindergarten to early school age with MMR vaccine immunization history has not been elucidated. This study aimed to describe the immunity profile of children from kindergarten to early school age to identify the susceptible population. In Jiangsu Province, a cross-sectional survey of 4- to 8-year-old children who were vaccinated with at least one dose of MMR vaccine was conducted. IgG antibody results were analyzed by employing both the Enzyme-Linked Immunosorbent Assay (ELISA) cutoff values and the mixture model. A total of 7436 eligible subjects were enrolled: 3386 subjects were in kindergarten, and 4450 were in primary school. The overall seroprevalence (75.4%, 95% CI: 74.4%-76.4%) and Geometric mean concentration (GMC, 201.4U/ml, 95% CI: 194.1-209.4) of mumps antibodies in 2016 were low. The seroprevalence of children in kindergarten (78.1%, 95% CI: 76.6%-79.4%) was significantly higher than that of children in primary school (73.2%, 95% CI: 71.2%-74.6%). The GMC was negatively correlated with the time of inoculation (F = 32.17, P = 0.002). The mixture model enables a more comprehensive understanding of serological results by investigating four levels of antibody response, suggesting that there is a small fraction of the population with waning immunity. Children in kindergarten and primary school whom had received one dose of MMR vaccine were at a higher risk of mumps infection, particularly the 7-year-old group in the central region. Therefore, the single-dose MMR vaccine schedule has a limited impact on mumps control and prevention, and a two-dose MMR vaccine schedule should be introduced. PMID- 29792547 TI - A method to quantify genotoxicity of malathion in rainbow trout using the weighted averaging. AB - DNA breakage has been frequently used as a biomarker of the pesticide toxicity. The present study introduced a method to quantify the DNA breakage in Oncorhynchus mykiss exposed to the pesticide malathion. Specimens were exposed to different concentrations of malathion for 1-9 days and their gill and liver were sampled. DNA was extracted and electrophoresed using agarose gel. The pixel density curves were obtained from the gel smears. The area under the curves was arbitrarily divided from three up to seven segments using a Java macro in the software ImageJ. Some weighted averaging methods were used to calculate DNA breakage in each gel lane. Akaike information criterion (AIC) was used to find the best analysis of variance. The liver was more sensitive than the gill showing a larger number of significant differences among the specimens exposed to various concentrations of malathion. The geometric weighted averaging on the data extracted from the seven-segment pixel density curve resulted to the lowest AIC. The double-strand DNA breakage of O. mykiss was able to detect malathion in freshwater in concentrations over 0.05 mg L-1. PMID- 29792548 TI - Comparison of the Ocular Penetration and Pharmacokinetics Between Natamycin and Voriconazole After Topical Instillation in Rabbits. AB - PURPOSE: To investigate the ocular penetration of natamycin (NAT) and voriconazole (VRC) after topical instillation in New Zealand white rabbits using simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high performance liquid chromatography. METHODS: Seventy-eight healthy rabbits were randomly divided into 3 groups. In the first 2 groups, 72 rabbits were used for single-dose testing (36 for NAT, 36 for VRC), in which 50 MUL of 5.0% NAT or 1.0% VRC was instilled into the rabbits' left eyes. In the 3rd group, 6 rabbits were used for repeated-dose testing in which 50 MUL of 5.0% NAT was instilled into their left eyes 12 times (once per hour) during the daytime. These animals were sacrificed immediately to collect their aqueous humors and corneas. RESULTS: After a single topical instillation, the highest concentrations in the cornea and aqueous humor for VRC were 34.1 MUg/g and 14.7 MUg/mL, respectively. The permeability ratios of aqueous/cornea were from 0.1 to 1.26. The highest concentrations in cornea and aqueous humor for NAT were 299.3 ng/g and 27.1 ng/mL, respectively. The permeability ratios of aqueous/cornea were from 0.02 to 0.23. In the repeated-dose group, the NAT concentrations in the cornea and aqueous humor were 10,569 ng/g and 54.4 ng/mL, respectively. The permeability ratio was as low as 0.0051. CONCLUSION: The better corneal penetration of VRC suggests that it is more suitable for deep corneal fungal infections than NAT via topical ocular administration. PMID- 29792550 TI - Reply to "A refugee patient with meningococcal meningitis type B." PMID- 29792549 TI - Analysis of the effects of individual- and community- level predictors on migrant children's primary immunization in Yiwu city, east China. AB - BACKGROUND: To evaluate the effects of a wide range of individual- and community level factors on migrant children's primary immunization. METHODS: Migrant children aged 13-24 months (born from 1 June 2013 to 31 May 2014) were surveyed in Yiwu city, in June 2015. Social-demographic factors and vaccination records were collected. Five factors at community-level including community wealth, distance to the nearest immunization clinic, maternal education, antenatal clinic (ANC) visits, and hospital delivery were constructed. The relationship between individual- and community-level factors and a child's vaccination status for Chinese primary immunization were evaluated by logistic regression model and the adjusted odds ratio (AOR) with the p-values and 95% confidence interval (CI) were calculated. RESULTS: The community wealth (aOR:1.4; 95% CI:1.1-2.7), the community maternal education (aOR:1.8; 95% CI:1.4-4.5), the community ANC visits (aOR:1.8; 95% CI:1.3-2.8), and the community hospital delivery (aOR:2.2; 95% CI:1.6-4.8) were positively associated with the completeness of primary immunization, while community distance to the nearest immunization clinic was negatively associated with the completeness of primary immunization (aOR:0.7; 95% CI:0.5-0.9). The coverage of completeness of primary immunization was higher among children living in rural areas than those living in urban areas (aOR:1.7; 95% CI: 1.3-3.1). CONCLUSIONS: In order to achieve better vaccination coverage among migrant children in Yiwu, as well as to close the gaps and disparities of acceptability and accessibility in childhood vaccination in urban areas, policy makers should design interventions based on the factors addressed in this study. PMID- 29792551 TI - Aponeurosis influences the relationship between muscle gearing and force. AB - Aponeuroses are connective tissues found on the surface of pennate muscles and are in close association with muscle fascicles. In addition to transmitting muscle forces to the external tendon, aponeurosis has been hypothesized to influence the direction of muscle shape change during a contraction. Muscle shape changes affect muscle contractile force and velocity because they influence the gear ratio with which muscle fascicles transmit force and velocity to the tendon. If aponeurosis modulates muscle shape changes, altering the aponeurosis' radial integrity with incisions should alter gearing. We tested the hypothesis that incising the aponeurosis would lead to decreased gearing across force conditions with an in situ preparation of the turkey lateral gastrocnemius muscle. We found that multiple full-length incisions in the aponeurosis altered the relationship between gearing and force relative to the intact aponeurosis condition. Specifically, after multiple aponeurosis incisions, gear ratio decreased by 19% in the high-force contractions compared with the intact condition. These results suggest that aponeuroses influence muscle shape change and can alter muscle contractile force and speed through their effect on muscle gearing. NEW & NOTEWORTHY Muscle gearing is determined by muscle shape change during a contraction and varies with the force of contraction. Variable gearing influences muscle force and speed, but how gearing is modulated is not well understood. Incising the aponeurosis before and after contractions demonstrates that aponeurosis plays a role in modulating gearing. PMID- 29792552 TI - Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle. AB - Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMP dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-h-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue. NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilization-induced rapid development of insulin resistance in skeletal muscle. PMID- 29792553 TI - Mitochondrial complex I defect resulting from exercise-induced lower limb ischemia in patients with peripheral arterial disease. AB - This study aims to compare the structural and mitochondrial alterations between muscle segments affected by exercise-induced ischemia and segments of the same muscle without ischemia, in the same subject. In a prospective analysis, 34 patients presenting either peripheral arterial disease or chronic coronary syndrome without any evidence of peripheral arterial disease were eligible for inclusion based on findings indicating a need for either a femoro-popliteal bypass or a saphenous harvesting for coronary bypass. Before surgery, we assessed the level of exercise-induced ischemia in proximal and distal sections of the thigh by the measurement of transcutaneous oxygen pressure during an exercise treadmill test. Distal and proximal biopsies of the sartorius muscle were procured during vascular surgical procedures to assess mitochondrial function and morphometric parameters of the sartorius myofibers. Comparisons were made between the distal and proximal biopsies, with respect to these parameters. Thirteen of the study patients that initially presented with peripheral arterial disease had evidence of an isolated distal thigh exercise-induced ischemia, associated with a 35% decrease in the mitochondrial complex I enzymatic activity in the distal muscle biopsy. This defect was also associated with a decreased expression of the manganese superoxide dismutase enzyme and with alterations of the shapes of the myofibers. No functional or structural alterations were observed in the patients with coronary syndrome. We validated a specific model ischemia in peripheral arterial disease characterized by muscular alterations. This "Distal-Proximal Sartorius Model" would be promising to explore the physiopathological consequences specific to chronic ischemia. NEW & NOTEWORTHY We compared proximal versus distal biopsies of the sartorius muscle in patients with superficial femoral artery stenosis or occlusion and proof of, distal only, regional blood flow impairment with exercise oximetry. We identified a decrease in the mitochondrial complex I enzymatic activity and antioxidant system impairment at the distal level only. We validate a model to explore the physiopathological consequences of chronic muscle ischemia. PMID- 29792554 TI - Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial. AB - Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 +/- 10, 87 +/- 9, and 91 +/- 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 +/- 11 vs. 57 +/- 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction. PMID- 29792555 TI - Vaccine hesitancy among caregivers and association with childhood vaccination timeliness in Addis Ababa, Ethiopia. AB - INTRODUCTION: Vaccines are vital to reducing childhood mortality, and prevent an estimated 2 to 3 million deaths annually which disproportionately occur in the developing world. Overall vaccine coverage is typically used as a metric to evaluate the adequacy of vaccine program performance, though it does not account for untimely administration, which may unnecessarily prolong children's susceptibility to disease. This study explored a hypothesized positive association between increasing vaccine hesitancy and untimeliness of immunizations administered under the Expanded Program on Immunization (EPI) in Addis Ababa, Ethiopia. METHODS: This cross-sectional survey employed a multistage sampling design, randomly selecting one health center within five sub-cities of Addis Ababa. Caregivers of 3 to 12-month-old infants completed a questionnaire on vaccine hesitancy, and their infants' vaccination cards were examined to assess timeliness of received vaccinations. RESULTS: The sample comprised 350 caregivers. Overall, 82.3% of the surveyed children received all recommended vaccines, although only 55.9% of these vaccinations were timely. Few caregivers (3.4%) reported ever hesitating and 3.7% reported ever refusing a vaccine for their child. Vaccine hesitancy significantly increased the odds of untimely vaccination (AOR 1.94, 95% CI: 1.02, 3.71) in the adjusted analysis. CONCLUSIONS: This study found high vaccine coverage among a sample of 350 young children in Addis Ababa, though only half received all recommended vaccines on time. High vaccine hesitancy was strongly associated with infants' untimely vaccination, indicating that increased efforts to educate community members and providers about vaccines may have a beneficial impact on vaccine timeliness in Addis Ababa. PMID- 29792556 TI - Effect of Wii training on hand function in children with hemiplegic cerebral palsy. AB - OBJECTIVE: The purpose of this study was to investigate the effect of Wii training on hand function in children with hemiplegic cerebral palsy. METHODS: A randomized controlled trial was conducted in 40 children with hemiplegic cerebral palsy (8-12 years). The experimental group received Wii training involving four games for 40 minutes a day, three times a week for 12 weeks plus usual care. The control group received usual care alone. Outcomes were spasticity measured using the modified Ashworth scale, grip strength measured using dynamometry, and hand function measured using the Peabody developmental motor scale (2nd ed.). Outcomes were measured at baseline and after 12 weeks of intervention. RESULTS: Spasticity in the experimental group decreased by 0.4 out of 4.0 (95% CI 0.1 to 0.8) more than the control group by 12 weeks. Power grip strength increased by 1.6 kg (95% CI 0.7 to 2.5) and pinch grip strength by 1.2 kg (95% CI 0.8 to 1.6) more than the control group by 12 weeks. Hand function increased by 6 out of 52 (95% CI 5 to 7) more than the control group by 12 weeks. CONCLUSION: Wii training plus usual care decreases spasticity and increases grip strength and hand function in children with hemiplegic cerebral palsy. PMID- 29792557 TI - Improving vaccine-related pain, distress or fear in healthy children and adolescents-a systematic search of patient-focused interventions. AB - OBJECTIVE: The WHO recently highlighted the need for research into potential interventions that can be used to mitigate pain during mass vaccinations, in addition to interventions specific for adolescents. The current review examines the literature on potential interventions that can be used during mass vaccination settings in healthy individuals between the ages of 4 and 15 years old. METHODS: Criteria for inclusion were: 1)participants between the ages of 4 15 years, 2)interventions that were patient-focused, 3)vaccinations in healthy individuals, 4)outcome measures to include self-reported pain, fear or distress. RESULTS: Twenty-seven articles were identified with a total of 31 interventions. Eleven interventions used injection-site specific interventions, 17 used patient led interventions and three used a combination of both site-specific and patient led interventions. CONCLUSION: Interventions using coolant and vibration together, as well as a combination of site-specific and patient-led interventions, showed the most consistent effects in reducing self-reported pain, fear or distress. PMID- 29792558 TI - Epidemiologic features and intervention effect of fall injury among rural school aged children in southwest China: a short-term cohort study. AB - Falls are the top one type in all unintentional injuries. In this study, we aim to explore the epidemiological characteristics of falls and assess the intervention effect. Our research had interviewed 2854 rural children in southwest China. Then, we used School-Family-Individual (SFI) comprehensive education model to conduct an intervention among 1506 children and follow up them for one year. The changes in injury knowledge and incidence rate before and after intervention were compared. We found the fall injury was 37.32% (178/477) and ranked top one in the total injuries. After intervention, the children's fall injuries-related knowledge was significantly increased by 15.29 percent (P < 0.001). While falls incidence significantly decreased after- intervention (6.24% vs. 3.93%; P < 0.001). From the results we concluded that the falls rate was high and was the prior reason of all injuries. SFI intervention model can effectively reduce the incidence of the fall injury. PMID- 29792559 TI - Frozen White-Leg Shrimp (Litopenaeus vannamei) in Korean Markets as a Source of Aeromonas spp. Harboring Antibiotic and Heavy Metal Resistance Genes. AB - As the most consumed shrimp variety, white-leg shrimp (Litopenaeus vannamei) owns a high market demand in Korea. This study sought to screen the frozen white-leg shrimp for Aeromonas spp. harboring antimicrobial and heavy metal resistance characteristics. A total of 44 Aeromonas spp. strains were isolated and tested for antibiotic susceptibility and heavy metal tolerance followed by PCR-based detection of resistance genes and integrons. It was observed that resistance to ampicillin and oxacillin was 100% among isolates. Besides, 95%, 89%, 86%, 80%, 66%, and 43% of the isolates were resistant to nalidixic acid, tetracycline, cephalothin, streptomycin, trimethoprim-sulfamethoxazole, and imipenem, respectively, and less resistance to other antibiotics was also observed. Cr resistance was the highest (91%) among five heavy metals tested, whereas 57%, 32%, 20%, and 9% of the isolates were tolerant to Cu, Pb, Cd, and Hg, respectively. The PCR assays implied the presence of qnrB, qnrS, tetA, tetE, aac(6')-Ib, and aphAI-IAB, and intI1 genes among 80%, 77%, 18%, 30%, 9%, 0.25%, and 82% of the isolates, respectively. There were 35 (80%) integron 1-positive isolates harboring qacE2, dfrA1, orfC, orfD, aadB, catB3, oxa-10, and aadA1 genes in varying combinations. In addition, heavy metal resistance genes, CopA, merA, and CzcA were positive in 9%, 7%, and 27% of the isolates, respectively. According to these outcomes, the frozen white-leg shrimp in Korean markets can be suggested as a source of multidrug and heavy metal-resistant Aeromonas spp. that carries genetic determinants. PMID- 29792560 TI - Acceleration profile of an acrobatic act during training and shows using wearable technology. AB - The purpose of this study was to describe the mechanical characteristics of a trampoline circus act and its individual tracks performed in training and shows using a tri-axial accelerometer. A track is an artist's specific role within a choreographed act. Seven male acrobats performed their trampoline act during training and shows while wearing a triaxial accelerometer and reported ratings of perceived exertion (RPE) after each trial. Average acceleration (AVG), root mean square (RMS), root mean to the fourth (RM4), time spent in specific acceleration ranges and RPE were measured/recorded from training and show acts. Paired t-tests compared dependent variables between training and show. Acceleration AVG, RMS and RM4 were significantly higher (p < 0.05) in training than show. RPE was significantly higher (p < 0.05) in show than training. No significant differences existed in time spent in any of the acceleration ranges between training and show. GPS devices have been used to manage workloads in field sports but are inoperable in theatres. But, inertial measurements may be an effective alternative to describe mechanical demands in theatre or arena environments. Wearable technology may be useful to coaches to improve understanding of track demands to manage artist workloads. PMID- 29792561 TI - Testimonial Psychotherapy in Immigrant Survivors of Intimate Partner Violence: A Case Series. AB - Testimonial psychotherapy is a therapeutic ritual for facilitating the recovery of survivors of human rights violations that focuses on sharing the trauma narrative. Originally developed in Chile as a method for collecting evidence during legal proceedings, testimonial therapy has been widely applied transculturally as a unique treatment modality for populations that are not amenable to traditional Western psychotherapy. In this case report, we first review the literature on testimonial therapy to this date. We go on to describe how testimonial therapy has been specifically adapted to facilitate recovery for immigrant survivors of intimate partner violence (IPV). We present three Latin American women who underwent testimonial psychotherapy while receiving psychiatric treatment at a Northern Virginia community clinic affiliated with the George Washington University. The therapy consisted of guided trauma narrative sessions and a Latin- American Catholic inspired reverential ceremony in a Spanish-speaking women's domestic violence group. In this case series we provide excerpts from the women's testimony and feedback from physicians who observed the ceremony. We found that testimonial psychotherapy was accepted by our three IPV survivors and logistically feasible in a small community clinic. We conceptualize testimonial psychotherapy as a humanistic therapy that focuses on strengthening the person. Our case report suggests testimonial psychotherapy as a useful adjunct to formal psychotherapy for post-traumatic stress symptoms. PMID- 29792562 TI - Combined Effects and Cross-Interactions of Different Antibiotics and Polypeptides in Salmonella bredeney. AB - Salmonella spp. are health-threatening foodborne pathogens. The increasingly common spread of antibiotic-resistant Salmonella spp. is a major public healthcare issue worldwide. In this study, we wished to explore (1) antibiotic or polypeptide combinations to inhibit multidrug-resistant Salmonella bredeney and (2) the regulation of cross-resistance and collateral sensitivity of antibiotics and polypeptides. We undertook a study to select antibiotic combinations. Then, we promoted drug-resistant strains of S. bredeney after 15 types of antibiotic treatment. From each evolving population, the S. bredeney strain was exposed to a particular single drug. Then, we analyzed how the evolved S. bredeney strains acquired resistance or susceptibility to other drugs. A total of 105 combinations were tested against S. bredeney following the protocols of CLSI-2016 and EUCAST 2017. The synergistic interactions between drug pairings were diverse. Notably, polypeptides were more likely to be linked to synergistic combinations: 56% (19/34) of the synergistic pairings were relevant to polypeptides. Simultaneously, macrolides demonstrated antagonism toward polypeptides. The latter were more frequently related to collateral sensitivity than the other drugs because the other 13 drugs sensitized S. bredeney to polypeptides. In an experimental evolution involving 15 drugs, single drug-evolved strains were examined against the other 14 drugs, and the results were compared with the minimal inhibitory concentration of the ancestral strain. Single drug-evolved S. bredeney strains could alter the sensitivity to other drugs, and S. bredeney evolution against antibiotics could sensitize it to polypeptides. PMID- 29792563 TI - Ability of crime, demographic and business data to forecast areas of increased violence. AB - Identifying geographic areas and time periods of increased violence is of considerable importance in prevention planning. This study compared the performance of multiple data sources to prospectively forecast areas of increased interpersonal violence. We used 2011-2014 data from a large metropolitan county on interpersonal violence (homicide, assault, rape and robbery) and forecasted violence at the level of census block-groups and over a one-month moving time window. Inputs to a Random Forest model included historical crime records from the police department, demographic data from the US Census Bureau, and administrative data on licensed businesses. Among 279 block groups, a model utilizing all data sources was found to prospectively improve the identification of the top 5% most violent block-group months (positive predictive value = 52.1%; negative predictive value = 97.5%; sensitivity = 43.4%; specificity = 98.2%). Predictive modelling with simple inputs can help communities more efficiently focus violence prevention resources geographically. PMID- 29792565 TI - Anticipatory judgements associated with vision of an opponent's end-effector: An approach by motion perturbation and spatial occlusion. AB - This study was aimed at determining how the visual information of an end-effector (racket) and the intermediate extremity (arm) of a tennis server contribute to the receiver's anticipatory judgement of ball direction. In all, 15 experienced tennis players and 15 novice counterparts viewed a spatially occluded computer graphics animation of a tennis serve (no-occlusion, racket-occlusion, and body occlusion) and made anticipatory judgements of ball direction on a visual analogue scale (VAS). The patterns of the serve motions were generated by a simulation technique that computationally perturbs the rotation speed of the selected racket-arm joint (forearm pronation and elbow extension) on a captured serve motion. The results suggested that the anticipatory judgements were monotonically attuned with the perturbation rate of the forearm pronation speed excepting under the conditions of the racket-occlusion model. Although such attunements were not observed in the elbow perturbation conditions, the results of correlation analysis indicated that the residual information in the spatially occluded models had a similar effect to the no-occlusion model within the individual experienced participants. The findings support the notion that end effector (racket) provides deterministic cues for anticipation, as well as imply that players are able to benefit from the relative motion of an intermediate extremity (elbow extension). PMID- 29792566 TI - Clues to an Evolutionary Mystery: The Genes for T-Toxin, Enabler of the Devastating 1970 Southern Corn Leaf Blight Epidemic, Are Present in Ancestral Species, Suggesting an Ancient Origin. AB - The Southern corn leaf blight (SCLB) epidemic of 1970 devastated fields of T cytoplasm corn planted in monoculture throughout the eastern United States. The epidemic was driven by race T, a previously unseen race of Cochliobolus heterostrophus. A second fungus, Phyllosticta zeae-maydis, with the same biological specificity, appeared coincidentally. Race T produces T-toxin, while Phyllosticta zeae-maydis produces PM-toxin, both host-selective polyketide toxins necessary for supervirulence. The present abundance of genome sequences offers an opportunity to tackle the evolutionary origins of T- and PM- toxin biosynthetic genes, previously thought unique to these species. Using the C. heterostrophus genes as probes, we identified orthologs in six additional Dothideomycete and three Eurotiomycete species. In stark contrast to the genetically fragmented race T Tox1 locus that encodes these genes, all newly found Tox1-like genes in other species reside at a single collinear locus. This compact arrangement, phylogenetic analyses, comparisons of Tox1 protein tree topology to a species tree, and Tox1 gene characteristics suggest that the locus is ancient and that some species, including C. heterostrophus, gained Tox1 by horizontal gene transfer. C. heterostrophus and Phyllosticta zeae-maydis did not exchange Tox1 DNA at the time of the SCLB epidemic, but how they acquired Tox1 remains uncertain. The presence of additional genes in Tox1-like clusters of other species, although not in C. heterostrophus and Phyllosticta zeae-maydis, suggests that the metabolites produced differ from T- and PM-toxin. PMID- 29792567 TI - Effects of age and body mass index on breast characteristics: a cluster analysis. AB - : Limited research has quantified variation in the characteristics of the breasts among women and determined how these breast characteristics are influenced by age and body mass. The aim of this study was to classify the breasts of women in the community into different categories based on comprehensive and objective measurements of the characteristics of their breasts and torsos, and to determine the effect of age and body mass index on the prevalence of these breast categories. Four breast characteristic clusters were identified (X-Large, Very ptotic & Splayed; Large, Ptotic & Splayed; Medium & Mildly-ptotic; and Small & Non-ptotic), with age and BMI shown to significantly affect the breast characteristic clusters. These results highlight the difference in breast characteristics exhibited among women and how these clusters are affected by age and BMI. The breast characteristic clusters identified in this study could be used as a basis for future bra designs and sizing systems in order to improve bra fit for women. Practitioner summary: This original research provides evidence for bra designers and manufacturers on the diverse breast characteristics exhibited by women within the population and the significant effect that both body mass index and age have on the breast characteristic clusters. Future bra designs should consider the variation in breast characteristics among women. ABBREVIATIONS: BMI: Body Mass Index; UBCC: Under-bust chest circumference. PMID- 29792568 TI - Physical ergonomics awareness in an offshore processing platform among Malaysian oil and gas workers. AB - INTRODUCTION: The reliability of offshore oil and gas (O&G) facilities depends on the operation and maintenance activities, where human physical intervention is involved. Workers are often exposed to ergonomics hazards due to inefficient workplace design. Ergonomics awareness among workers is a crucial factor in mitigating such hazards. OBJECTIVES: This study intends to evaluate the state of physical ergonomics awareness among Malaysian O&G workers and to assess their perception toward the criticality of physical ergonomics issues within an offshore processing facility. METHODS: Data were collected through online questionnaire distribution. The respondents were required to evaluate three sections of the questionnaire to reflect their state of physical ergonomics awareness: design criteria in an offshore workplace that are related to physical ergonomics; effects of physical ergonomics implementation in design; criticality of physical ergonomics issues. RESULTS: The results showed a good level of physical ergonomics awareness among respondents without them being influenced by dissimilar experiences (engineering design and operation/maintenance) and the range of experience in an offshore workplace. CONCLUSION: This study provides an overview of Malaysian O&G workers' outlook toward the physical ergonomics issues in an offshore workplace. These data could be further analyzed in future as relevant aspects of designing an offshore facility. PMID- 29792569 TI - The Relationship between Suicidal Responses and Traumatic Brain Injury and Severe Insomnia in Active Duty, Veteran, and Civilian Populations. AB - This study examined how a positive traumatic brain injury (TBI) screening and insomnia severity relate to suicidal outcomes across active duty, veteran, and civilian samples. Data were used from 3,993 participants from 19 studies. We conducted a series of analyses by group to identify which significantly differed on the variables of interest. TBI and insomnia each had independent relationships with outcomes over and above the impact of the other factor. Veterans presented as clinically worse across the outcomes. However, the relationship between insomnia and suicidal responses was stronger for active duty military compared to veterans. Continued research on TBIs and insomnia severity across groups will improve quality of care for those at risk of suicide. PMID- 29792564 TI - Cognitive and Behavioral Resilience Among Young Gay and Bisexual Men Living with HIV. AB - PURPOSE: HIV/AIDS disproportionately affects young gay, bisexual, and other men who have sex with men (Y-GBMSM). Resilience remains understudied among Y-GBMSM living with HIV, but represents a potentially important framework for improving HIV-related outcomes in this population. We sought to explore cognitive and behavioral dimensions of resilience and their correlates among Y-GBMSM to gain insights to inform future interventions. METHODS: Our study sample consisted of 200 Y-GBMSM living with HIV enrolled in a multisite study of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). Participants completed a one-time, self-administered structured questionnaire, including validated scales capturing a range of cognitive, behavioral, demographic, and psychosocial data. Utilizing these data, we examined cognitive and behavioral dimensions of resilience and their potential psychosocial correlates using linear regression modeling. RESULTS: Multiple regression analyses demonstrated that education, stigma, social support, ethnic identity, internalized homonegativity, and behavioral resilience were statistically significant predictors of cognitive resilience (P < 0.001, R2 = 0.678). Social support satisfaction and cognitive resilience were significant predictors of behavioral resilience (P < 0.001, R2 = 0.141). CONCLUSIONS: Our findings point to potential strategies for incorporating resilience-promoting features into future interventions to support Y-GBMSM living with HIV. Specifically, strengths-based interventions in this population should seek to enhance social support, promote positive identity development, and encourage education. Future research can also seek to utilize and refine our measures of resilience among youth. PMID- 29792570 TI - A model for predicting the risk of musculoskeletal disorders among computer professionals. AB - OBJECTIVE: This study aimed to develop a model for predicting the risk of musculoskeletal disorders among computer professionals. MATERIALS AND METHODS: A preliminary study with a modified Nordic musculoskeletal questionnaire was conducted to identify the risk in different body parts of the professionals during their work. A discrete postural evaluation of the dynamic postures involved in the work was assessed using rapid upper limb assessment. Postural, physiological and work-related factors were considered as attributes of the model. The model was developed using various machine learning algorithms, and was then tested and validated. RESULTS: The postural factor of the computer professionals was found to be significantly (p < 0.01) correlated with the musculoskeletal disorders. Results of the logistic regression analysis showed that physiological and work-related factors were also significantly (p < 0.05) associated with musculoskeletal disorders. The Random Forest algorithm and Naive Bayes Classifier predicted the risk of musculoskeletal disorders with the highest accuracy (81.25%). CONCLUSION: Postural, physiological and work-related factors contribute to the development of musculoskeletal disorders. The Random Forest algorithm or Naive Bayes Classifier model developed based on these factors could be used to accurately predict the risk of musculoskeletal disorders among computer professionals at any instance of time, during their work. PMID- 29792571 TI - Extracorporeal Membrane Oxygenation and Temperature Management in Postresuscitation. PMID- 29792573 TI - Inherent Resistance to 14alpha-Demethylation Inhibitor Fungicides in Colletotrichum truncatum Is Likely Linked to CYP51A and/or CYP51B Gene Variants. AB - Anthracnose disease, caused by Colletotrichum truncatum, affects marketable yield during preharvest production and postharvest storage of fruits and vegetables worldwide. Demethylation inhibitor (DMI) fungicides are among the very few chemical classes of single-site mode of action fungicides that are effective in controlling anthracnose disease. However, some species are inherently resistant to DMIs and more information is needed to understand this phenomenon. Isolates of C. truncatum were collected from the United States and China from peach, soybean, citrus, and begonia and sensitivity to six DMIs (difenoconazole, propiconazole, metconazole, tebuconazole, flutriafol, and fenbuconazole) was determined. Compared with DMI sensitive isolates of C. fructicola, C. siamense, and C. fioriniae (EC50 value ranging from 0.03 to 16.2 ug/ml to six DMIs), C. truncatum and C. nymphaeae were resistant to flutriafol and fenbuconazole (with EC50 values of more 50 ug/ml). Moreover, C. truncatum was resistant to tebuconazole and metconazole (with resistance factors of 27.4 and 96.0) and displayed reduced sensitivity to difenoconazole and propiconazole (with resistance factors of 5.1 and 5.2). Analysis of the Colletotrichum spp. genome revealed two potential DMI targets, CYP51A and CYP51B, that putatively encode P450 sterol 14alpha demethylases. Both genes were identified and sequenced from C. truncatum and other species and no correlation between CYP51 gene expression levels and fungicide sensitivity was found. Four amino acid variations L208Y, H238R, S302A, and I366L in CYP51A, and three variations H373 N, M376L, and S511T in CYP51B correlated with the DMI resistance phenotype. CYP51A structure model analysis suggested the four alterations may reduce azole affinity. Likewise, CYP51B structure analysis suggested the H373 N and M376L variants may change the conformation of the DMI binding pocket, thereby causing differential sensitivity to DMI fungicides in C. truncatum. PMID- 29792574 TI - Evaluation of a Mobile Application for Pelvic Floor Exercises. AB - BACKGROUND: Pelvic floor exercises are effective in improving muscle strength and urinary incontinence symptoms. Increasingly popular mobile applications can be effective in teaching patients these exercises. INTRODUCTION: A mobile application, Bwom(c), aims to educate women about pelvic floor exercises with individually tailored plans relevant to the user's risk factors. The objective of this study is to assess the understandability and actionability of Bwom. MATERIALS AND METHODS: This is a cross-sectional survey of patients and providers at an academic medical center. The survey utilized the Patient Education Material Assessment Tool (PEMAT) validated by the U.S. Department of Health Services, which provides scores on understandability and actionability. Participants completed an initial demographic survey, used Bwom for 2 weeks, and then completed the PEMAT tool. RESULTS: Twenty five patients and 22 providers participated in the study, for a total of 47 participants. Providers included gynecology residents and faculty (91%), pelvic floor physical therapists (5%), and other healthcare professionals (5%). The majority of patients were age 31-40 (70%) and Caucasian (55%). Thirty nine percent had not yet tried pelvic floor exercises on their own before the study. The mean understandability score was 93.8% (+/-11.7) and the mean actionability score was 91.7% (+/-16.3). DISCUSSION: This study paves the way for future investigations into the effectiveness of this app in decreasing symptoms of pelvic floor weakness and incontinence. CONCLUSIONS: This study demonstrates that Bwom shows promise as a mobile application to educate women about pelvic floor exercises by providing user friendly actions in an understandable way. PMID- 29792576 TI - Using a deep learning network to recognise low back pain in static standing. AB - Low back pain (LBP) remains one of the most prevalent musculoskeletal disorders, while algorithms that able to recognise LBP patients from healthy population using balance performance data are rarely seen. In this study, human balance and body sway performance during standing trials were utilised to recognise chronic LBP populations using deep neural networks. To be specific, 44 chronic LBP and healthy individuals performed static standing tasks, while their spine kinematics and centre of pressure were recorded. A deep learning network with long short term memory units was used for training, prediction and implementation. The performance of the model was evaluated by: (a) overall accuracy, (b) precision, (c) recall, (d) F1 measure, (e) receiver-operating characteristic and (f) area under the curve. Results indicated that deep neural networks could recognise LBP populations with precision up to 97.2% and recall up to 97.2%. Meanwhile, the results showed that the model with the C7 sensor output performed the best. Practitioner summary: Low back pain (LBP) remains the most common musculoskeletal disorder. In this study, we investigated the feasibility of applying artificial intelligent deep neural network in detecting LBP population from healthy controls with their kinematics data. Results showed a deep learning network can solve the above classification problem with both promising precision and recall performance. PMID- 29792572 TI - GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics. AB - Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver. Tris-GalNAc binds to the Asialoglycoprotein receptor that is highly expressed on hepatocytes resulting in rapid endocytosis. While the exact mechanism of escape across the endosomal lipid bilayer membrane remains unknown, sufficient amounts of siRNAs enter the cytoplasm to induce robust, target selective RNAi responses in vivo. Multiple GalNAc-siRNA conjugate clinical trials, including two phase III trials, are currently underway by three biotech companies to treat a wide variety of diseases. GalNAc-siRNA conjugates are a simple solution to the siRNA delivery problem for liver hepatocytes and have shown the RNAi (and antisense oligonucleotide) field the path forward for targeting other tissue types. PMID- 29792577 TI - Serious Consequences of Malnutrition and Delirium in Frail Older Patients. AB - Malnutrition is highly prevalent in geriatric patients and is associated with an increased risk of death. In addition, delirium is a common condition of the older hospitalized patients. As brain has a high nutritional requirement, malnutrition may play an important role in cognitive dysfunction including the development of delirium. This study investigated the association between delirium and malnutrition in frail older patients and the effects on adverse outcomes. It was found that 75% of the patients with delirium suffered from malnutrition indicating that malnutrition contributes to the development of delirium in older hospitalized patients. Patients suffering from both malnutrition and delirium had a four times higher mortality in one month follow-up, a seven times increased rate of discharge to nursing homes and three days more in hospital. All older patients should routinely be assessed for malnutrition and delirium at admission to hospital and to prevent the development of delirium a close follow-up must take place to ensure adequate nutrition. PMID- 29792578 TI - It Is Official: Vector-Borne and Zoonotic Diseases in the United States and Territories on the Rise-Now What? PMID- 29792579 TI - Effects of Essential Oil from Thymus vulgaris on Viability and Inflammation in Zebrafish Embryos. AB - Innate immunity provides the initial response against pathogens and includes the inflammatory response. Regulation of the initiation and duration of neutrophil and mononuclear cell influx during inflammation determines both the successfulness of pathogen elimination and the level of resulting tissue damage. Zebrafish embryos provide excellent opportunities to visualize the inflammatory response. Neutrophil granules may be stained with Sudan black, and variation in neutrophil counts may be used to monitor the level of the response. Inflammation may be triggered by injuring the caudal fin, providing an opportunity for testing possible anti-inflammatory compounds in a whole-animal system. The use of homeopathic compounds as anti-inflammatory treatments is common in alternative medicine. Effects of unfractionated essential oil from Thymus vulgaris and its specific component, carvacrol, have been examined in cells in culture and in rodents. Our work extends this research to zebrafish, and includes toxicity and morphological studies as well as examination of anti-inflammatory effects following tail fin injury. Our results show that zebrafish are more sensitive to thyme oil compared to cells in culture, that cardiac defects arise due to thyme oil treatment, and that thyme oil reduces neutrophil infiltration during an inflammatory response. PMID- 29792580 TI - The Influence of Attentional Focus on Balance Control over Seven Days of Training. AB - This study examined the training effect of attentional focus (external focus, internal focus, or no focus instructions) on a dynamic balance task. Participants completed baseline balance testing, seven consecutive days of dynamic balance board training, and retention testing 24 hours after the last session. The novel finding of this study was the presence of a training effect on balance control when adopting an external focus relative to an internal focus or no focus instructions. Further, we report the unique observation that more patterned behavior was adopted regardless of the focus instructions. These findings provide insight into how instructions can be altered to enhance human balance control and complement the constrained-action hypothesis. PMID- 29792582 TI - Advancing Child Sexual Abuse Prevention in Schools: An Exploration of the Effectiveness of the Enough! Online Training Program for K-12 Teachers. AB - Child sexual abuse (CSA) in schools and educator misconduct represents a threat to the safety and well-being of our children. The Enough! Preventing Child Sexual Abuse in My School program is a 1-hour online training course developed to address the problem of sexual misconduct and CSA in K-12 education via the use of two avatars/teachers who are navigating CSA and misconduct in their schools. One hundred and thirty-four teachers from three school districts participated in a study to examine the effectiveness of the program in terms of knowledge awareness, including prevalence rates, types of CSA behaviors, impact of CSA on children, signs and symptoms, reporting responsibilities and responses to suspected abuse. Participants were randomly assigned to intervention and control groups: the intervention group (A) received the Enough! training and completed a pre-/posttest and an evaluation of the training (n = 61), Group B (control) completed the posttest only (n = 55), and Group C (control) completed both the pre- and posttests (n = 18). Results indicated that the intervention group's knowledge was significantly higher than that of the control group's at posttest. Group A participants reported a high level of satisfaction in the training, as well as increased knowledge, awareness and willingness to take action in the future. This study points to the need to further test the effectiveness of the Enough! program (and programs like it) on a wider-basis in an effort for educators to be better prepared to protect from the threat of CSA and sexual misconduct. PMID- 29792583 TI - Educator Sexual Misconduct and Texas Educator Discipline Database Construction. AB - The purpose of this research is to describe Texas educator sexual misconduct (ESM) by examining 8 years of sanctions issued to educators (N = 1415) for either sexual misconduct or inappropriate relationships with students or minors. We first examine Texas ESM from the perspective of quality database construction and then describe the demographic characteristics of educators sanctioned for ESM between 2008 and 2016. Differences in the demographic characteristics of educators sanctioned for ESM vary according to the definition of ESM employed by the state education agency. Younger and early career educators are more likely to engage in inappropriate relationships with students or minors, whereas older and later-career teachers are more likely to engage in sexual misconduct as that term is defined by the state education agency. Over one-third of educators sanctioned for ESM were either new to the profession or new to their school district when sanctioned. Recommendations are offered for database construction, policy, and practice. PMID- 29792581 TI - Victimization and Violence: An Exploration of the Relationship Between Child Sexual Abuse, Violence, and Delinquency. AB - Child sexual abuse (CSA) continues to be a major public health issue with significant short- and long-term consequences. However, little contemporary research has examined the relationship between CSA and delinquent and violent behavior in adolescence. Children who have been sexually abused experience a unique form of victimization compared to children who have endured other forms of maltreatment, as CSA can result in feelings of shame, powerlessness and boundary violations. The purpose of this study was to examine the effect of CSA on delinquent and violent behavior in adolescence. We examined self-report data at the age 18 interview from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) on measures of sexual abuse experience, and engagement in delinquent and violent behavior in the past year. All participants reported either a history of maltreatment or were identified at-risk based on demographic risk factors. Participants included 368 males and 445 females who self-reported experiences of CSA and delinquent and violent behavior (N = 813). Findings indicated that, when controlling for gender and race, the odds of engagement in delinquent and violent behavior for those who have experienced CSA are 1.7 times higher than for those who have not. Additionally, female victims of CSA were .52 times less likely to engage in violent and delinquent behavior compared to their male counterparts. Further efforts are needed to examine the effects of CSA on violent and delinquent behavior to better guide treatment efforts that prevent juvenile justice involvement. PMID- 29792584 TI - Neonatal intake of oleanolic acid attenuates the subsequent development of high fructose diet-induced non-alcoholic fatty liver disease in rats. AB - Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47 49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD. PMID- 29792585 TI - Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC): primary analysis from a Canadian open-label study of vortioxetine in patients with major depressive disorder (MDD). AB - OBJECTIVE: The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE). METHODS: Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch). The primary endpoint was the correlation between changes in patient-reported cognitive symptoms (20 item Perceived Deficits Questionnaire [PDQ-D-20]) and changes in work productivity loss (Work Limitations Questionnaire [WLQ]) at week 12. Additional assessments included changes in symptom and disease severity, cognitive performance, functioning, work loss, and safety. RESULTS: In the week 12 primary analysis, 196 eligible patients at 26 Canadian sites were enrolled, received at least one treatment dose, and attended at least one postbaseline study visit. This analysis demonstrated a significant, strong correlation between PDQ-D-20 and WLQ productivity loss scores (r=0.634; p<0.001), and this correlation was significant in both first treatment and switch patients (p<0.001). A weaker correlation between Digit Symbol Substitution Test and WLQ scores was found (r= 0.244; p=0.003). CONCLUSION: At 12 weeks, improvements in cognitive dysfunction were significantly associated with improvements in workplace productivity in patients with MDD, suggesting a role for vortioxetine in functional recovery in MDD. PMID- 29792586 TI - The incubation period of hepatitis E genotype 1: insights from pooled analyses of travellers. AB - Hepatitis E virus genotype 1 (HEV G1) is an important cause of morbidity and mortality in Africa and Asia. HEV G1's natural history, including the incubation period, remains poorly understood, hindering surveillance efforts and effective control. Using individual-level data from 85 travel-related HEV G1 cases in England and Wales, we estimate the incubation period distribution using survival analysis methods, which allow for appropriate inference when only time ranges, rather than exact times are known for the exposure to HEV and symptom onset. We estimated a 29.8-day (95% confidence interval (CI) 24.1-36.0) median incubation period with 5% of people expected to develop symptoms within 14.3 days (95% CI 10.1-21.7) and 95% within 61.9 days (95% CI 47.4-74.4) of exposure. These estimates can help refine clinical case definitions and inform the design of disease burden and intervention studies. PMID- 29792587 TI - Child abuse potential in mothers with early life maltreatment, borderline personality disorder and depression. AB - BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. METHOD: The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. RESULTS: ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. CONCLUSIONS: History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone. PMID- 29792588 TI - Candida kantuleensis sp. nov., a d-xylose-fermenting yeast species isolated from peat in a tropical peat swamp forest. AB - Three strains (DMKU-XE11T, DMKU-XE15 and DMKU-XE20) representing a single novel anamorphic and d-xylose-fermenting yeast species were obtained from three peat samples collected from Khan Thulee peat swamp forest in Surat Thani province, Thailand. The strains differed from each other by one to two nucleotide substitutions in the sequences of the D1/D2 region of the large subunit (LSU) rRNA gene and zero to one nucleotide substitution in the internal transcribed spacer (ITS) region. Phylogenetic analysis based on the combined sequences of the ITS and the D1/D2 regions showed that the three strains represented a single Candida species that was distinct from the other related species in the Lodderomyces/Candida albicans clade. The three strains form a subclade with the other Candida species including Candida sanyaensis, Candida tropicalis and Candida sojae. C. sanyaensis was the most closely related species, with 2.1-2.4 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene, and 3.8-4.0 % nucleotide substitutions in the ITS region. The three strains (DMKU-XE11T, DMKU XE15 and DMKU-XE20) were assigned as a single novel species, which was named Candida kantuleensis sp. nov. The type strain is DMKU-XE11T (=CBS 15219T=TBRC 7764T). The MycoBank number for C. kantuleensis sp. nov. is MB 824179. PMID- 29792589 TI - Using average nucleotide identity to improve taxonomic assignments in prokaryotic genomes at the NCBI. AB - Average nucleotide identity analysis is a useful tool to verify taxonomic identities in prokaryotic genomes, for both complete and draft assemblies. Using optimum threshold ranges appropriate for different prokaryotic taxa, we have reviewed all prokaryotic genome assemblies in GenBank with regard to their taxonomic identity. We present the methods used to make such comparisons, the current status of GenBank verifications, and recent developments in confirming species assignments in new genome submissions. PMID- 29792590 TI - Altererythrobacter flavus sp. nov., isolated from mangrove sediment. AB - A Gram-negative, aerobic, non-motile, rod-shaped bacterium, designated MS1-4T, was isolated from mangrove sediment of the Jiulong River Estuary, Fujian Province, China. The isolate formed yellow colonies on ZB 2216E agar. Optimal growth was observed at pH 6.0, at 34 degrees C and in the presence of 4 % (w/v) NaCl. Strain MS1-4T shared highest 16S rRNA gene sequence similarity of 97.7 % with Altererythrobacter mangrovi C9-11T, followed by Altererythrobacter ishigakiensis JPCCMB0017T (97.2 %). Phylogenetic analysis indicated that strain MS1-4T formed a clade with A. mangrovi C9-11T within the genus Altererythrobacter. The main cellular fatty acid was summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and the sole respiratory quinone was ubiquinone Q 10. The main polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and glycolipids. The G+C content of the DNA was 60.4 mol%. Based on data from this polyphasic characterization, strain MS1-4T should be classified as representing a novel species in the genus Altererythrobacter, for which the name Altererythrobacter flavus sp. nov. is proposed. The type strain is MS1-4T (=MCCC 1K02683T=NBRC 112977T). PMID- 29792591 TI - Comprehensive evolutionary and phylogenetic analysis of Hepacivirus N (HNV). AB - Hepaciviruses (HVs) have been detected in several domestic and wild animals and present high genetic diversity. The actual classification divides the genus Hepacivirus into 14 species (A-N), according to their phylogenetic relationships, including the bovine hepacivirus [Hepacivirus N (HNV)]. In this study, we confirmed HNV circulation in Brazil and sequenced the whole genome of two strains. Based on the current classification of HCV, which is divided into genotypes and subtypes, we analysed all available bovine hepacivirus sequences in the GenBank database and proposed an HNV classification. All of the sequences were grouped into a single genotype, putatively named 'genotype 1'. This genotype can be clearly divided into four subtypes: A and D containing sequences from Germany and Brazil, respectively, and B and C containing Ghanaian sequences. In addition, the NS3-coding region was used to estimate the time to the most recent common ancestor (TMRCA) of each subtype, using a Bayesian approach and a relaxed molecular clock model. The analyses indicated a common origin of the virus circulating in Germany and Brazil. Ghanaian sequences seemed to have an older TMRCA, indicating a long time of circulation of these viruses in the African continent. PMID- 29792592 TI - 43 degrees Convegno Nazionale di Studi di Medicina Trasfusionale, Genova, 23-25 maggio 2018. PMID- 29792593 TI - 2018 Canadian Urological Association guideline for Peyronie's disease and congenital penile curvature. PMID- 29792596 TI - A Swiss army knife for targeting receptors. AB - A compound can change the activity of NMDA receptors in some regions of a synapse without affecting those in other regions. PMID- 29792595 TI - BRG1 governs glucocorticoid receptor interactions with chromatin and pioneer factors across the genome. AB - The Glucocorticoid Receptor (GR) alters transcriptional activity in response to hormones by interacting with chromatin at GR binding sites (GBSs) throughout the genome. Our work in human breast cancer cells identifies three classes of GBSs with distinct epigenetic characteristics and reveals that BRG1 interacts with GBSs prior to hormone exposure. The GBSs pre-occupied by BRG1 are more accessible and transcriptionally active than other GBSs. BRG1 is required for a proper and robust transcriptional hormone response and knockdown of BRG1 blocks recruitment of the pioneer factors FOXA1 and GATA3 to GBSs. Finally, GR interaction with FOXA1 and GATA3 binding sites was restricted to sites pre-bound by BRG1. These findings demonstrate that BRG1 establishes specialized chromatin environments that define multiple classes of GBS. This in turn predicts that GR and other transcriptional activators function via multiple distinct chromatin-based mechanisms to modulate the transcriptional response. PMID- 29792594 TI - An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups. AB - N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations. Modest changes to the chemical structure interconvert negative and positive modulation. All modulators share the ability to enhance agonist potency and are use-dependent, requiring the binding of both agonists before modulators act with high potency. Data suggest that these modulators, including both enantiomers, bind to the same site on the receptor and share structural determinants of action. Due to the modulator properties, submaximal negative modulators in this series may spare NMDAR at the synapse, while augmenting the response of NMDAR in extrasynaptic spaces. These modulators could serve as useful tools to probe the role of extrasynaptic NMDARs. PMID- 29792598 TI - [Poisson Noise Removal Using Patch-order Resampling PCA Algorithm]. AB - The problem of Poisson denoising is common in various photon-limited imaging applications, especialy in low-light imaging, astronomy and nuclear medical applications. Due to the smal sample problem and the related insufficient self similarity between patches of whole image, many denoising algorithms cannot obtain the favorable denoising performance. We propose patch-order resampling PCA algorithm for Poisson noise reduction. Firstly, we use the patch-ordered operations to sort the extracted image patches and exploit the bootstrap resampling method to resample the different blocks of spectral images to obtain more data matrix of image samples. Then, we select the patches with largest weights corresponding to the vectors of image samples data matrix as the most similar patches. Finaly, we use principal component analysis algorithm for processing the image to obtain the final denoised image. Experiments results show that the proposed method achieves excelent Poisson noise removal performance in the photon-limited images with smal sample problems. PMID- 29792597 TI - Increasing plant diversity with border crops reduces insecticide use and increases crop yield in urban agriculture. AB - Urban agriculture is making an increasing contribution to food security in large cities around the world. The potential contribution of biodiversity to ecological intensification in urban agricultural systems has not been investigated. We present monitoring data collected from rice fields in 34 community farms in mega urban Shanghai, China, from 2001 to 2015, and show that the presence of a border crop of soybeans and neighboring crops (maize, eggplant and Chinese cabbage), both without weed control, increased invertebrate predator abundance, decreased the abundance of pests and dependence on insecticides, and increased grain yield and economic profits. Two 2 year randomized experiments with the low and high diversity practices in the same locations confirmed these results. Our study shows that diversifying farming practices can make an important contribution to ecological intensification and the sustainable use of associated ecosystem services in an urban ecosystem. PMID- 29792599 TI - [Research of Wireless Ultrasonic Doppler Fetal Heart Detection System]. AB - Fetal heart rate (FHR) is an important index to the fetal health evaluation. Therefore, the study of the system is of great significance to the monitoring of FHR. In this paper, the detection principle, the overal framework of the system, hardware composition, PC software interface and so on have been made a detailed implements. The display of instant heart rate, heart rate trendline, and fetal heartbeat have been achieved. A large amount of test data of this system has been got by fetal feart simulator testing in the laboratory and preliminary clinical tests in the hospital. The testing result showed that using the system can achieve good accuracy and repeatability. PMID- 29792600 TI - [Application of RFID and Big data in Surgical Instruments Usage Analysis and Performance Tracking]. AB - Through the use of RFID technology, the project carries out life-cycle tracking on the surgical instruments, and analyzes the quality control, performance, supply, maintenance, replacement and new disposition of the surgical instruments. Through the large data accumulated by the system, the medical devices are purchased, used and guaranteed. The establishment of quality control and operation of the important management assessment system, can effectively improve the management of surgical instruments use efficiency. PMID- 29792601 TI - [Development of System of Measuring Multiple Physiological Parameters by Special Cushion]. AB - In order to monitor the physiological condition of the human body in daily life, this study has designed a system of measuring physiological parameters based on cushion, which could detect heart rate and respiration rate when people are sitting. The system can continuously colect signal from cushion with a state of low pressure and without sticking any electrode on people's bodies. The hardware part mainly includes the signal acquisition circuit of the sensor, microcomputer control module and Bluetooth wireless transmission module. For the two physiological signals have the characteristic of the large noise and low frequency, we use the Butterworth low-pass filter to process the signal according to an optimized Matlab algorithm. The results show that this system can measure heart rate and respiration rate accurately. Thus, the real-time monitoring on body's information can be implemented. PMID- 29792602 TI - [Collaborative Work Based on Heterogeneous Systems:a New Mode of Hospital Information System]. AB - Hospital information technology has introduced a new mode of colaborative work based on heterogeneous systems and it wil become the new norm. The article ilustrates some successful typical cases of information exchange in the heterogeneous systems for colaborative work in Chinese PLA general hospital and puts forward some principles in the hospital's design of heterogeneous information systems. PMID- 29792603 TI - [A Safe and General Type of Convenient Installation and Instantly Removable A shaped Scalpel Handle]. AB - Objective: In order to overcome the disadvantages of the common single handle cold scalpel such as cicatrix cutting inefficient, large amount of skin losses, margin concave and convex, cutting marks poor healing, a safe and general type of convenient instalation and instantly removable"A"shaped scalpel handle was developed. Methods: For the convenience of the single hand independent, cicatrix cutting smoothly and conveniently, man-machine design"A"shaped scalpel handle and application. Results: The"A"shaped scalpel handle has good precision and controllability. When loading or unloading the blades, it's convenient, efficient and safe, free choice of direction. Conclusion: The"A"shaped scalpel handle with cicatrix cutting single hand is independent, universal for al blades, can conveniently instal and instantly remove, is portable and easy to storage, has wide range of applications. The prevention of sharp instrument injuries reduces the occupation injury risks and improves operation efficiency PMID- 29792604 TI - [Research Progress of Articular Cartilage Scaffold Materials for Tissue Engineering]. AB - Articular cartilage injury is common in clinical in recent years, due to the trauma or bone disease. There are many methods for the repair of articular cartilage injury currently, but each has its limitations. With the development of nanotechnology and bionic-technology, the scaffold plays an important role with tissue engineering technique in the repair of articular cartilage injury, in which the composite materials are the hot direction of the research and development, the ful application of nanotechnology and bionic-technology prospect in the future. PMID- 29792605 TI - [High-risk Active Implantable Medical Devices Standards]. AB - Objective: Comprehensive standards of active implantable medical devices with high risks are required by China's current industrial development, and standard problems and ideas are discussed in this paper. Methods: Analysis of the status of China's active implantable medical device standards and international standards. For the booming field for active implantable medical devices with high risks, international standard's problems, ideas and trends are analyzed. Results: Bottleneck of the development of China's active implantable medical device standards is the lack of Chinese medical devices industry actual independent research and development capability. China's independent standard research on the basis of independent core technology of active implantable medical devices is the opportunity to promote the internationalization of China standard. Conclusion: Improving the standards of active implantable medical devices based on independent core technology, combined with problems of existing international standards, to further improve and develop international standards and lead high level international technical standards. PMID- 29792606 TI - [Safety Evaluation of the Leachable Substances of High Polymer Material Products]. AB - Combined with the characteristics of polymer material properties and contact with the human body, this paper investigates safety evaluation necessary, general evaluation strategies, specific research ideas and methods of leachable substances in polymer material products in order to provide reference for the researcher and reviewer of this kind of products from the point of risk control. PMID- 29792607 TI - [Application and Safety Evaluation of Bisphenol A in Medical Instruments]. AB - Bisphenol A (BPA) is widely used in the production of medical instruments, and has direct or indirect contacts with the human body through the digestive tract, respiratory tract, blood and other ways to enter the body. At present, the main regulatory for bisphenol A is focus on the food packaging and products for babies. There is no clear limits made for the use of bisphenol A in medical instruments. Government lacks the safety evaluation for the application of bisphenol A in the medical instruments. There are imperfections in the regulation and supervision of the potential risks in the application of bisphenol A. The release of bisphenol A when using medical instruments could lead to potential harmful impact on human's health, it is necessary to evaluate the safety of bisphenol A in medical instruments. PMID- 29792608 TI - [The Hemostatic Effect and Safety Evaluation Tests of Soluble Hemostatic Gauze]. AB - Objective: The aim of this paper is to study the hemostasis and security of soluble hemostatic gauze in the rabbit liver hemorrhage model. Methods: After making the rabbit liver hemorrhage model, the control group used sterile gauze to stop bleeding, the positive control group used TISTAT to stop bleeding, the test group used soluble hemostatic gauze to stop bleeding. Hemostasis, blood loss and animal clinical symptoms were measured. Liver and kidney parameters, along with histopathology were recorded and analyzed. Transmission electron microscopy examination was also done. Results: The blood loss is cut back and hemostasis is shortened in the test group. Other tests have no difference with the control group. Conclusion: No toxic effects on rabbit are found in the test group. The hemostatic effects have no difference with positive control group. PMID- 29792609 TI - [Discussion on the Monitoring of Medical Device Adverse Event]. AB - Objective: Analyzing the status of medical device adverse events, the function of the clinical medical engineers in medical device adverse event monitoring was investigated. Methods: Through introducing the functions of the various departments in the medical device adverse event monitoring, the technical requirements and management responsibilities of clinical medical engineer and medical staff were defined. Results: Enhancing the function of clinical medical engineers in medical device adverse event monitoring,which is an effective measure to prevent medical device adverse events. Conclusion: Play the functions of clinical engineers in the medical device adverse event monitoring, which is significant to improve the using quality of medical devices and to ensure patient safety. PMID- 29792611 TI - [Testing Efifciency Stability of Light Energy Transfer in Endoscope Lighting Optical Cable Using Gray Scale Measurement]. AB - This paper proposes a new testing method used for medical endoscope lighting optical cable. It compares the experiment result from gray scale measurement and the one from the traditional luminous flux measurement. It proposes the idea that we can apply the gray scale measurement to other feature testing of the endoscope as well. PMID- 29792610 TI - Relationship of receptors of adipokines with hypertension and obesity. Murine model AB - Background: The aim of this paper is to investigated the contribution of adipose tissue thought the adipokines and kidney failure (KF) Methods: In male rats were fed with a standard lab diet (C) or a hypercaloric diet including 30% sucrose; obese group (Ob) and obese with kidney failure group (Ob/KF). We evaluated the changes of adipokines under conditions of obesity and KF, using 5/6 surgeryto induce vascular injury. The anterior and media branches of the left kidney artery were tied together, leaving the posterior branch viable to enable the kidney to function. The right kidney was removed. Results: A 90% survival rate of the animals was achieved due to special care taken. Kidney function progressively decreased after surgery. Compared with the control group, in the other two groups (Ob and Ob/KF) the level of leptin increased and that of adiponectin decreased (p < 0.01). Post-surgery increases were observed in blood pressure, lipids, creatinine and insulin (p < 0.01). Conclusion: This model is proposed for the study pathophysiological mechanisms that lead to obesity and complications of kidney or cardiovascular function. PMID- 29792613 TI - [Research on the Application of Lean Management in Medical Consumables Material Logistics Management]. AB - Objective: Solve the problems of high cost, low utilization rate of resources, low medical care quality problem in medical consumables material logistics management for scientific of medical consumables management. Methods: Analysis of the problems existing in the domestic medical consumables material logistics management in hospital, based on lean management method, SPD(Supply, Processing, Distribution) for specific applications, combined HBOS(Hospital Business Operation System), HIS (Hospital Information System) system for medical consumables material management. Results: Achieve the lean management in medical consumables material purchase, warehouse construction, push, clinical use and retrospect. Conclusion: Lean management in medical consumables material can effectively control the cost in logistics management, optimize the alocation of resources, liberate unnecessary time of medical staff, improve the quality of medical care. It is a scientific management method. PMID- 29792612 TI - [CT Quality Control Test from the Second Level 2nd Class Hospitals in Shanghai]. AB - The purpose of this study is to assess the present situation about the overal performance quality of CT scanners from Second Level 2nd Class hospitals and private hospitals in Shanghai. The test and evaluation methods refer to Specification for Quality Assurance Test for Computed Tomography X-ray Scanners (GB 17589-2011). A total of 62 CT scanners from 59 hospitals were tested. The mean value of high-contrast resolution was 6.8 lp/cm, low contrast detectability was 2.4, CT number of water was 3.0 HU, noise was 0.43% and uniformity was 2.3 HU. In quality control tests, 20 of 62 CT scanners were qualified, and the percent of pass was only 32%. The equipment aging and lack of preventive maintenance were main reasons for performance degradation of CT scanners. PMID- 29792615 TI - [Application of Image Plate in Quality Assurance of Medical Accelerator]. AB - Objective: To explore the value of Computed Radiography(CR) in quality control for the medical linear accelerator. Methods: By using both CR and autoradiography film respectively, we tested the alignment of light fields with radiation fields, colimator rotation with center, couch rotation with center and multi-leave colimators(MLC) position accuracy of medical linear accelerator. Each tests were carried out ten times repetitive colection. Then compared the differences between this two methods. Results: There were no significant difference between CR and autoradiography film in the same grup(P>0.05). Conclusion: CR can be used in quality control for the medical linear accelerator since it can meet quality control requirements of radiotherapy. PMID- 29792614 TI - Ocular evisceration etiology AB - Background: The aim of this paper was to determine the most common etiology of ocular evisceration in a tertiary-level hospital. Methods: Observational and retrospective study in the Ophthalmology Department from January 2013 to December 2016 at the Centro Medico Nacional Siglo XXI. Results: Of the 54 eviscerations, exogenous endophthalmitis was found 25.90%, ocular trauma 22.2%, painful blind eye 14.8%, perforated corneal ulcer and endogenous endophthalmitis both in 13% and perforated infectious corneal ulcers 11.1%; 70.4% were associated with systemic comorbidities and 79.6% were associated with ophthalmologic comorbidities. Conclusions: Exogenous endophthalmitis is the most frequent evisceration; the loss of an eyeball, has important social and labor impact, and economic for the Instituto Mexicano del Seguro Social. PMID- 29792616 TI - [The Solution of Improving Radiotherapy Quality]. AB - Improving radiotherapy quality is the core connotation of radiotherapy technician work. This paper summarizes the status of technician work in the department, finds the existing problems and proposes solution. Through the implementation of solution, radiotherapy quality is improved. It has reference value for safe use of radiotherapy equipment and promoting position accuracy. PMID- 29792617 TI - [The Resolution of Wet Wrap Bag after Disinfected in the Pulsation Sterilizer]. AB - Our hospital has instaled a couple of high temperature and high pressure pulsation sterilizers. However, after the process of disinfection and sterilization, we found that many non-woven bags in which wrapped the contaminated medical devices were wet. This abnormal phenomenon continuously has happened a couple of times. Having excessive condensed water inside the wrap bag wil severely affect the sterilization effect, so we did a scrupulous survey of the phenomenon and the structure of the machine and the steam boiler. At last, we came up with a perfect solution, that is, to make a redesign of the steam boiler and the steam conveying pipeline network. PMID- 29792618 TI - [Study on the Characteristics of EMG Signal of the Masticatory Muscles in Different Materials]. AB - Objective: To investigate the activities of different soft and hard materials during right chewing masticatory muscles, describing the masticatory muscles of time domain and frequency domain features. Methods: 11 experimental subjects who conform to the standards of measurement chew two materials of different soft and hard texture. Then record surface EMG of each bilateral temporalis anterior bundle, masseter, two bilateral anterior abdominal muscles, analysis to 5 kinds of characteristics of the study of EMG. Results: When subjects chewing different soft and hard materials, al the EMG features in the bilateral anterior temporalis and masseter values had significant difference (P < 0.05). The results in bilateral digastric anterior abdominal except zero crossing rate have significant difference; median frequency on the right side of the masticatory muscle has decreased trend. Conclusion: The anterior temporalis and masseter EMG active more intense when chewing hard objects; the right side of the masticatory muscles have obvious fatigue trend after chewing hard masticatory 30 cycles. PMID- 29792623 TI - [The Automatic X-ray Radiological Positions Detection Based on Contour and Gary Feature Matching]. AB - Objective: Designed a method that can automatically distinguish the X-ray radiological positions based on image information. : For any selected input clinical X-ray digital images, we extract the image outline in the edge detection method using optimal threshold selection, then process binarization. After compared with the whole body phantom X-ray images, then process gray level similarity traverse detection. : By optimizing the decision, the best matching region of the same input film was obtained, and the imaging part of the patient is determined based on prior knowledge. : The algorithm is fast and has a high degree of robust. PMID- 29792624 TI - [A Drug Delivery Device for Drug-eluting Stents Simulating the Cardiovascular Blood Flow Pattern]. AB - A novel drug delivery device simulating the cardiovascular bloodfl ow pattern was introduced. The device was used to simulate the in vivo drug release in the drug eluting stents. The results regarding the drug release rate were subject to the pattern from in vivo measurement. Therefore, the device was validated as a measurement method for in vivo drug release rate. PMID- 29792625 TI - [Electrical Stimulation System with Surface Electromyography Feedback]. AB - Currently, various kinds of electrical stimulation equipment are used in the rehabilitation of muscle function for patients with hemiplegia, but many defects can be found in those designs, for example, insufficient feedback parameter, unsynchronized information, unintuitive display and so on. Therefore, this study introduces an electrical stimulation system with surface electromyography (sEMG) feedback based on LabVIEW, which combines with multi-channel sEMG acquisition, electrical stimulator and other hardware system. This system can not only provide a wide electrical stimulation parameters range for frequency, pulse width and intensity, but also acquire sEMG during the treatment. Meanwhile, this system can compute iEMG, CCR, RMS and MPF in real-time. The verification results shows that the whole system is effective and stable. This system can help physicians observe the muscle condition of different patients, who can explore suitable electrical stimulation parameters to design individualized treatment projects. PMID- 29792626 TI - [Eyes-Brain-Hands Coordination Training System for Mental Retarded Children]. AB - In order to help improving mental attention and sensory integration ability of mental retarded children, this paper proposes an interactive eyes-brain-hands coordination training system. This system realizes the principle of seeing, thinking and moving of hands by an interactive operation between the computer software custom icons and a touch control panel, so it can improve cognitive function and activity of daily living. The results show this training platform has a high degree of application and acceptance, and provides a portable training method for mental retarded children. PMID- 29792627 TI - [Discussion on the Hospital Mobile Workstation Architecture]. AB - With the development of internet technology, the wireless network now has become an indispensable part of people's life. Wireless networks and the mobile terminal began to spread inthe medical areas. Many foreign hospitals have mobile internet technology for hospital medical work, some large domestic hospitals also try to work in this area, and have got some clinicaly practical. In our institute, there has launched a mobile medical construction work, this paper is about our hospital construction of mobile medical platform work. PMID- 29792628 TI - [The Key Technology Study on Cloud Computing Platform for ECG Monitoring Based on Regional Internet of Things]. AB - This paper explores the methods of building the internet of things of a regional ECG monitoring, focused on the implementation of ECG monitoring center based on cloud computing platform. It analyzes implementation principles of automatic identifi cation in the types of arrhythmia. It also studies the system architecture and key techniques of cloud computing platform, including server load balancing technology, reliable storage of massive smalfi les and the implications of quick search function. PMID- 29792629 TI - [A Linear Transmit Design of Ultrasound System Based on AD9106]. AB - The linear transmit solution is considered as one of the technologies which can improve the signal to noise ratio (SNR) of the transmit channel of the medical ultrasound system effectively. A linear transmit design based on AD9106 is introduced. The design can reduce the system design complexity and achieve the desired functionality of the different imaging modes and techniques. PMID- 29792630 TI - [Study of the Anti-corrosion and Anti-fretting Properties of Surfi cial Treated magnesium Alloy Bone Plate]. AB - The weakening of mechanical properties caused by rapid degradation has been an impediment to the clinical application of magnesium aloy for a long time. In this paper, the effect of surface treatment on the anti-corrosion and anti-fretting properties of magnesium aloy ZK60 was studied. Firstly, an oxidizing layer whose outer layer was porous was first made on the surface of magnesium aloy through micro-arc oxidation treatment (MAO). Then ahydroxyapatitecoating was fabricated by electrodeposition on the oxidizing layer to seal the porous layer. The corrosion resistance and fretting performance of them were investigated in vitro under a simulated bone-plate service condition. Polarization testing results showed that both of them can signifi cantly enhanced the corrosion resistance of magnesium aloy and the corrosion resistance of the latter was better. The fretting testing results showed that obvious coatingfl aking occurred on the worn surface of the latter, and its anti-fretting properties are inferior to that of the former. PMID- 29792631 TI - [ECG Signal Processing Methods and Application]. AB - Hospital ECG detection is divided into detection EEG and Holter ECG detection.This paper mainly summarizes ECG signal denoising, detection methods of each band, compression and transmission of ECG and ECG classification algorithms. PMID- 29792632 TI - [Present Situation and Thinking on the Reform of the Classifi cation and Regulation of Medical Devices in China]. AB - This paper introduces the domestic device regulatory classifi cation. Risk factors of medical equipment are analyzed. Combined with the analysis of the present situation of medical device regulatory classifi cation in china, this paper puts forward advice to reform and improve China's medical device regulatory classifi cation system. PMID- 29792633 TI - [Development of Implantable Medical Device Traceability Management Information System]. AB - Objective: Using modern information technology means to manage implant medical traceability. Methods: Collect and analyze the implantable medical device traceability management problems inside, combine with their own work practice, learn from the advanced methods of other industry and foreign key links for traceability management and process of study and analysis, find out the model, scheme and basic requirements for the traceability management by network. Results: Design and develop an information system for traceability management of implant medical instruments, including the flow of goods, supervision, traceback and employing the traceability. Conclusion: The system well regulates the traceability management system, unifies the traceability management processes, improves the efficiency of traceability management. The design of this system also conforms to the future development of traceability management direction, many aspects also meet needs of administrations, the medical departments and the users. PMID- 29792634 TI - [Analysis on the Common Problems of Second Type of Passive Medical Device Registration in Jiangxi Province under the New Laws and Regulations]. AB - In this paper, the common problems of the registration of second type of passive medical devices in the implementation process of the new regulations in Jiangxi province were analyzed, and some suggestions for improvement were put forward. PMID- 29792635 TI - [The Reflection on Common Problems of Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery Clinical Studies]. AB - Resorbable adhesion barrier devices for use in abdominal and/or pelvic surgery are high-risk implantable medical devices. There are some difficulties in their clinical research. This article summarizes and analyzes the common problems of resorbable adhesion barrier devices for use in abdominal and/or pelvic surgery clinical studies from the perspective of technical review, in order to provide reference for Chinese manufacturers and investigators in the design of clinical studies and clinical research. PMID- 29792636 TI - [Analysis of Adverse Events in Clinical Use of Catheter]. AB - In recent years, with the extensive use of various clinical catheter, Adverse events in the clinical catheter products also showed an upward trend. Here we wil review the common adverse event performance, risk point and reasons of AEs adverse events about the catheter during the clinical use, through a large number of clinical research, visit and literature review, in order to provide evidence to support in reducing the incidence of catheter clinical adverse events, and prevent recurrence and spread of the serious adverse events during the using of process. PMID- 29792637 TI - [Investigation on the Allocation of Nursing Devices in Liaoning Province]. AB - In this article,the nursing devices alocation information of 294 hospitals, including the origin, purchase time, funding sources, failure rate and satisfaction with the performance, efficiency, and after-sales services, is surveyed by convenient sampling. The confi guration and application of nursing devices in Liaoning Province is known. It is hoped to be helpful for providing a reference for the demand of nursing device market. PMID- 29792638 TI - [Bone Tomography Scan Optimization in SPECT/CT Equipment of Nuclear Medicine]. AB - Objective: To study and search for a balance between the image quality and acquisition speed in tomography of whole body bone scan. Methods: Adjustments of acquisition conditions were carried out gradualy every two months since April 2014. The qualities of fused SPECT/CT images were diagnosed by three doctors. Then the picture would be evaluated comprehensively by analyzing image quality and image resolution after adjusting image acquisition conditions. Results: Seven kinds of image acquisition conditions taken were in line with diagnostic requirements. The third method is extended to clinical work best. Conclusion: To obtain a high colection effi ciency, parameters of bone tomography acquisition can be set a frame of 5 seconds, total 64 (5.625o), automatic probe close and continuous scanning. Also recommends the use of "continuous" instead of "step and shoot" approach in bone SPECT acquisition. tomography, emission-computed, single photon, bone tomography, program optimization. PMID- 29792639 TI - [Results of Five-year Quality Control Program and the Change of QA Mode for Helical Tomotherapy Machine]. AB - Helical tomotherapy (HT), as a new IMRT technology, utilizes a fan beam of radiation for treatment. It combines the main characteristics of a modern CT scanner and a linear accelerator to achieve the function of helical tomotherapy. Due to the complexity of the system with a highly integrated and automated features, monitoring its operation, continuing to improve the stability and reliability, and simplifying its quality control procedures has become an important part of quality assurance (QA) for HT. Based on the results of afi ve year quality control (QC) program, and the initial application of new QA equipment, this study wil summarize the standardization mode of its QA and explore the changes of QA mode. PMID- 29792640 TI - [Serial Cases of Troubleshooting of NeuViz CT]. AB - The article describes the specifi c examples of fault maintenance of the Neusoft NeuViz series CT, so as toprovide some maintenance references for coleagues. PMID- 29792641 TI - [Seven Cases of Troubleshooting and Analysis on VARIAN IX Medical Linear Accelerator]. AB - This paper briefly introduced seven cases of malfunctions occurred in the VARIAN IX linear accelerator during operation, i.e., control board malfunction of electronic gun (GFIL interlock), modulator malfunction (HVCB interlock), energy programming board malfunction (EXQ1), energy conversion potentiometer malfunction (CARR interlock), MLC malfunction, thermostat valve malfunction (PUMP interlock) and ionization chamber malfunction (ION interlock). Moreover, malfunction cases analyzed and troubleshooting methods presented in this paper can provide reference for colleagues. PMID- 29792642 TI - [Variation of SpO2 during a Step-wise Paced Breathing Procedure]. AB - Rhythmic respiratory movement in a deep and slow pattern can be beneficial to cardiovascular system, this paper investigates the effect of step-wise paced breathing procedure on blood oxygen saturation (SpO2). Experiment objects were divided into two groups, the normobaric hypoxia (simulated altitude of 4 500 meters hypoxia environment, 8 persons), normoxia and normobaric group (laboratory environment, 49 persons). The respiratory movements were performed by a high-to low progressive change in two groups respectively. During the experiment, each object's blood oxygen saturation and heart rate were recorded. Results showed that progressive guided breathing could significantly increase the subjects' blood oxygen saturation level from 90% to 95% under the hypoxic condition. Even under the normobaric and normoxic condition, progressive guided breathing with stable blood oxygen saturation level can also enhance the blood oxygen saturation level. In both groups, mean heart rate declined in the progressive guided breathing. The research showed that the step-wise paced breathing technique could regulate the blood oxygen saturation and effectively improve the level of blood oxygen saturation by adjusting the respiratory motion in the low oxygen environment. PMID- 29792643 TI - [Influence Factors on Analyzing Transmission Time of Relative Blood Volume Based on Ultrasonic]. AB - Ultrasound-based measurement of relative blood volume can be used to assess patient's dry weight during hemodialysis. The results of relative blood volume were calculated from the ultrasonic transmission time measurement in the arteriol pot, and the accuracy of transmission time measurement is directly related to the reliability of the results of relative blood volume. There are various factors which influence the travel time, this article analyzed patients themselves, measuring device and the external factors, and advised appropriate counter measures. PMID- 29792645 TI - [A Novel and Fast P Wave Detection Algorithm in ECG Signals]. AB - This paper presents a new, simple and fast algorithm of automated P wave detection in multi-lead ECG Signals. Range of QRS-T complex is detected firstly. Then QRS-T complex is eliminated. Final y, P wave's onset and offset are detected by using the average of low-pass difference method and tangent method. Tangent method is always used to locate the offset of T Wave but it wil firstly be used to locate the P wave onset and offset in this paper. The proposed algorithm is tested by the annotated CSE database. Result shows that algorithm test result has a good consistency with BIS CSE annotation. Compared with the mean and standard deviation of P wave onset and offset, our algorithm and CSE annotation is-2.01 ms, 3.94 ms and 4.96 ms, 5.86 ms. PMID- 29792644 TI - [Method of Permissible Source Region Selection Based on FMT Image and CT Data]. AB - In Fluorescence Molecular Tomography (FMT), the reconstruction and fusion display of inner light source can be realized with the aid of CT data. A method is proposed in this paper to select permissible source region based on FMT image and CT data. The position and depth of light source can be estimated in FMT image. According to the coordinate relation of the two mode image, the light source position can be marked in CT data and mesh was produced on the marked CT data. Experimental results show that, the method can reduce the ill-posedness of the inverse problem and improve the accuracy of reconstruction of inner light source. PMID- 29792646 TI - [Wireless Passive Body Sensor for Temperature Monitoring Using Near Field Communication Technology]. AB - In this study, we designed a wireless body temperature sensor (WBTS) based on near field communication (NFC) technology. Just attaching the WBTS to a mobile phone with NFC function, the real-time body temperature of human subjects can be acquired by an application program without seperate power supply. The WBTS is mainly composed of a digital body temperature probe (d-BTP), a NFC unit and an antenna. The d-BTP acquires and processes body temperature data through a micro control er, and the NFC unit and antenna are used for wireless energy transmission and data communication between the mobile phone and WBTS. UART communication protocol is used in the communication between the d-BTP and NFC unit, and data compression technique is adopted for improving transmission efficiency and decreasing power loss. In tests, the error of WBTS is +/-0.1 oC, in range of 32 oC to 42 oC. The WBTS has advantages of high accuracy, low power loss, strong anti-interference ability, dispensation with independent power supply etc., and it can be integrated into wearable apparatuses for temperature monitoring and health management. PMID- 29792647 TI - [Development of Health Intelligent Management Cloud Platform on Maternal and Infant Monitor]. AB - Objective: Using the wireless mobile communication technology and Internet technology, cloud platform to build maternal and infant health intelligent management. Methods: Using the J2EE technology based on B/S three-tier to build health intelligent management cloud platform. Vital signs parameters (such as blood pressure, blood oxygen saturation, heart rate, breathing, pulse, temperature, instantaneous heart rate of pregnant women, etc) achieved the real time detection and wireless remote transmission. Results: Realized the digitization management of maternal health information, health records, health analysis; Through this platform to realize the consulting between the patient and doctor online. Conclusion: The Pregnant women can upload and download various vital signs parameters at any time to check the personal health analysis report through mobile phone client. PMID- 29792648 TI - Urological myriad. PMID- 29792649 TI - Network meta-analysis, a new statistical technique at urologists' disposal to improve decision making. PMID- 29792650 TI - Prostate Cancer - Local Treatment after Radiorecurrence: HIFU - High-Intensity Focused Ultrasound. PMID- 29792651 TI - Prostate Cancer - Local Treatment after Radiorecurrence: Surgery - Back to the future? PMID- 29792652 TI - Prostate Cancer - Local Treatment after Radiorecurrence: Salvage Cryoablation. PMID- 29792654 TI - [Design of ECG Signal Acquisition Terminal Based on ADS1298R]. AB - The home health monitoring of the ECG signal acquisition and display terminal is designed with MSP430F6659 and ADS1298R chip of TI company. The basic principles of ECG col ection is introduced in the beginning, and then the overal scheme of the system is described by MSP430F6659 and ADS1298R chip as the core, and the modules peripheral interface, real-time display in LCD, data storage and USB are introduced. The ECG signal acquisition terminal designed in this paper has the characteristics of smal size, low power consumption and so on. PMID- 29792653 TI - Editorial Comment: The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury. PMID- 29792655 TI - [Development of Magnetic Anastomosis Device for Colostomy]. AB - Introduction of a new magnetic anastomosis device for colostomy including its design and operaging principal. The anastomosis device is composed of magnetic base and anastomosis ring. It is convenient for colon and abdominal subcutaneous tissue going together through the magnetic attraction. The colostomy completes with magnetic compression anastomosis. The device has the advantage of making operation easer, reducing the operation steps and can better solve the colostomy ischemic necrosis, colostomy retraction, colostomy joint complications of skin mucous membrane and the skin diease around the colostomy. Patients can real y benefit from this device. PMID- 29792656 TI - [Integrated"U"Shaped Cutting Edge Rongeurs of Pruning Finger-Toe and Bending Truncating Pin]. AB - Objective: In order to overcome the problems that bone rongeur and Kirschner forcep's less function and easy damage, trivial and inefficient, bulky volume, bone and needle broken edge is not neat, needle tail easy spatter wounding and other defects, integrated "U" shaped cutting edge rongeurs of pruning finger-toe and bending-truncating pin is desigened. Methods: Pruning-truncating rongeurs set the trimming, bending and shearing, straight and twisting, loading and unloading, filing and stripping, string devices, aintenance functions and other functions in one, compare with bone rongeurs in clinical application. Results: Pruning truncating rongeurs are molding once, manipulation convenient, light and safe, anti damage and maintenance free, cost-effective. Conclusion: Pruning-truncating rongeurs are highly integrated and portable anti-lost, preparation instrument swift, man-machine coordination, sharp instrument injury prevention, to improve the operation efficiency. PMID- 29792657 TI - [Research of Kinematics and Kinetics Models of Human Knee Joint]. AB - Human knee joint as a research object, it has become an effective way to establish models of human knee joint. The types of human knee joint models are identified, and each type of model is simply introduced respectively. Focusing on the types of the kinematics and kinetics models of human knee joint on the basis of anatomy, the current research status is detailedly described and comprehensively analyzed at home and abroad correspondingly. Through in-depth study the various kinematics and kinetics models, and their advantages and limitations are discovered. The existing problems are summarized, solution and development trend are also proposed. PMID- 29792659 TI - [Study of Regulatory Requirements of Customized Device in the U.S.]. AB - This article introduces the regulatory requirements of customized device in the U.S. And it also proposes suggestion and reference through comparative study on relationship among customized device, humanitarian use device and 3D printing device,and on similarities and differences of American regulatory requirements between customized device, and humanitarian used device. PMID- 29792658 TI - [Study of Medical Devices Use-related Risk Based on Human Factors Engineering]. AB - This article briefly introduced human factors engineering concepts and depicts the risk management process for addressing use-related hazards, explained the important role of human factors engineering in elimination or reduction of use related hazards, and provides the general process of medical devices use-related risk study. Some advices are given to eliminate or reduce of use-related hazards of medical devices. PMID- 29792660 TI - Experience of status epilepticus in the Neurology department of a tertiary-level hospital in Mexico AB - Background: The status epilepticus is a neurological emergency that continues to be little identified early in emergency rooms and hospitalized patients, with significant morbidity and mortality. The aim of this paper was to establish the etiology and evolution of the status epilepticus in hospitalized patients in a tertiary-level hospital. Methodology: Descriptive, cross-analytical study of adult patients hospitalized with the diagnosis of epileptic status at a tertiary level hospital, between August 2010 and February 2016. Results: 19 patients, mean age 35 years +/- 19. With 15 years of convulsive epileptic status, 13 subjects with generalized seizures, 4 with alert alterations and 2 with focal seizures. In 4 cases, structural damage was detected, 4 due to non-specific inflammation, 2 due to Neuroinfection, 2 with anoxoischemic encephalopathy and 3 cases without evident etiology; of the 17 survivors, 10 with Rankin Scale modified from 4-5 points. Conclusions: The status epilepticus is a common diagnosis in third level centers, with significant morbi mortality. After a complete study protocol, the etiological diagnosis is reached in most cases. PMID- 29792661 TI - [Medical Device Adverse Events Primary Analysis on Esophageal Stents]. AB - Objective: To probe into the characteristics and influencing factors of ADR cases induced by Esophageal stents, so as to provide effective resolutions for safety use. Methods Methods: By retrieving published MDR cases induced by Esophageal stents in FDA MAUDE database and CNKI database, 153 cases of adverse events in MAUDE database from 2012 to 2015 and 96 valid documents between 1994 and 2015 were obtained, screened and analyzed retrospectively. Results: The main MDR performance were gastrointestinal bleeding, chest pain, foreign body sensation, etc, due to the risk inherent in the product or risk during use. Conclusion: The public safety of Esophageal stents use can be ensued according to perfecting related laws, establishing and regulating the MDR monitor system and strengthening the responsibility of authority, manufacturers, suppliers and medical institutions. PMID- 29792662 TI - [Testing Equipment on Vascular Mechanical Properties]. AB - The vascular mechanical parameters are important indicators for human vascular and they play important roles in clinical research. This paper developed a new vascular mechanical properties testing system. This system not only realizes the tensile rupture test in one dimensional, but also the reciprocating tensile test for vascular, which provides more comprehensive experimental data and theoretical basis for the study of human vascular. The system consists of three parts: the mechanical platform, hardware circuit and upper computer system. The mechanical platform transforms the rotation movement of motor into linear movement via the structure of bal screw. And the bal screw and tension sensor are connected, which is used for mechanical data reading. The displacement data is col ected by displacement sensor. Experiments show that the accuracy is better than 0.292%, and could meet the demand of the testing of vascular biomechanical characteristics. PMID- 29792663 TI - [Comparative Study on Two ECG Standards]. AB - The recording and analyzing ECG is able to measure and interpret ECG data, which is convenient for doctors' subsequent medical diagnosis, so in recent years it has rapid development. This ECG must implement YY 1139-2013 Diagnostic electrocardiographic devices standard, and YY 0782-2010 Medical electrical equipment-Part 2-51:Particular requirements for safety, including essential performance, of recording and analyzing single channel and multichannel of electrocardiographs standard. The two standards have links and differences. By analyzing, comparing, inducing two standards, this article sums up the links and differences of the two standards, describes the differences of the two standards between macro and micro point of views in detail, helps ECG testing personnel to deepen the understanding of the standard terms, and improve the detection efficiency of ECG. PMID- 29792664 TI - Tricolor White-Light-Emitting Carbon Dots with Multiple-Cores@Shell Structure for WLED Application. AB - The past few years have witnessed the rapid development of carbon dots (CDs) due to their outstanding optical properties and a wide range of applications. However, the design and control of CDs with long-wavelength multicolor emission are still huge challenges to be addressed for their practical use in different fields. Here, novel nitrogen-doped multiple-core@shell-structured AC-CDs with tricolor emissions of red, green, and blue were constructed via one-pot hydrothermal method from 5-amino-1,10-phenanthroline and citric acid as reactants and the growth process of AC-CDs was monitored with the reaction time in the synthetic system. The origin of different fluorescence emissions was explored using the unique coordination ability of the surface groups of AC-CDs. An obvious concentration dependence of fluorescent properties was observed for the as prepared AC-CDs, and a highly fluorescent quantum yield (QY) of 67% for red emission at 630 nm can be obtained by adjusting concentration of AC-CDs. The pure white-light emission (0.33, 0.33; Commission Internationale de l'Elcairage coordinate) was carried out from single carbon dot with QY of 29% through regulation of the excitation and concentration of multiple-core@shell-structured AC-CDs. In addition, because of their excellent photoluminescent properties, the white-emitting AC-CDs as emitting phosphor can be easily used in the fabrication of white-light-emitting diode with good anti-photobleaching and temperature stability. PMID- 29792665 TI - Highly Conductive and Robust Three-Dimensional Host with Excellent Alkali Metal Infiltration Boosts Ultrastable Lithium and Sodium Metal Anodes. AB - The direct utilization of metallic lithium and sodium as the anodes for rechargeable batteries would be highly advantageous, which has been considered as one of the most promising choices for next-generation high-energy-density storage devices. Although the induced safety concerns, inferior rate, and cycling performance severely hinder the commercialization of lithium metal batteries (LMBs) and sodium metal batteries (SMBs), the recent development of nanotechnology-based solutions really revives the lithium/sodium metal anodes for high-energy batteries. In this work, an ultrastable carbon textile (CT)-based host with excellent infiltration for both metallic Li and Na has been designed and exhibits more flat voltage profiles, lower stripping/plating overpotential, and better cycling stability both in symmetric cell and full cell configurations, even in additive-free carbonate-based electrolyte compared with pure Li/Na electrodes. The highly conductive and mechanically robust three-dimensional CTs not only offer a stable scaffold against hyperactive lithium and sodium but also enable uniform nucleation and growth during stripping/plating process, which effectively suppress the dendrite growth and stabilize the electrode dimension. This facile strategy provides new insights into the design of stable hosts with prestored alkali metal to address the multifaceted issues in LMBs and SMBs simultaneously. PMID- 29792666 TI - Chemical Evolution in Silicon-Graphite Composite Anodes Investigated by Vibrational Spectroscopy. AB - Silicon-graphite composites are under development for the next generation of high capacity lithium-ion anodes, and vibrational spectroscopy is a powerful tool to identify the different mechanisms that contribute to performance loss. With alloy anodes, the underlying causes of cell failure are significantly different in half cells with lithium metal counter electrodes compared to full cells with standard cathodes. However, most studies which take advantage of vibrational spectroscopy have only examined half-cells. In this work, a combination of FTIR and Raman spectroscopy describes several factors that lead to degradation in full pouch cells with LiNi0.5Mn0.3Co0.2O2 (NMC532) cathodes. The spectroscopic signatures evolve after longer term cycling compared to the initial formation cycles. Several side-reactions that consume lithium ions have clear FTIR signatures, and comparison to a library of reference compounds facilitates identification. Raman microspectroscopy combined with mapping shows that the composite anodes are not homogeneous but segregate into graphite-rich and silicon-rich phases. Lithiation does not proceed uniformly either. A basis analysis of Raman maps identifies electrochemically inactive regions of the anodes. The spectroscopic results presented here emphasize the importance of improving electrode processing and SEI stability to enable practical composite anodes with high silicon loadings. PMID- 29792667 TI - Control of Selectivity in Palladium(II)-Catalyzed Oxidative Transformations of Allenes. AB - Oxidation reactions play a central role in organic synthesis, and it is highly desirable that these reactions are mild and occur under catalytic conditions. In Nature, oxidation reactions occur under mild conditions via cascade processes, and furthermore, they often occur in an enantioselective manner with many of them involving molecular oxygen or hydrogen peroxide as the terminal oxidant. Inspired by the reactions in Nature, we have developed a number of Pd(II)-catalyzed cascade reactions under mild oxidative conditions. These reactions have an intrinsic advantage of step economy and rely on selectivity control in each step. In this Account, we will discuss the control of chemo-, regio-, and diastereoselectivity in Pd(II)-catalyzed dehydrogenative cascade coupling reactions. The enantioselective version of this methodology has also been addressed, and new chiral centers have been introduced using a catalytic amount of a chiral phosphoric acid (CPA). Research on this topic has provided access to important compounds attractive for synthetic and pharmaceutical chemists. These compounds include carbocyclic, heterocyclic, and polycyclic systems, as well as polyunsaturated open-chain structures. Reactions leading to these compounds are initiated by coordination of an allene and an unsaturated pi-bond moiety, such as olefin, alkyne, or another allene, to the Pd(II) center, followed by allene attack involving a C(sp3)-H cleavage under mild reaction conditions. Recent progress within our research group has shown that weakly coordinating groups (e.g., hydroxyl, alkoxide, or ketone) could also initiate the allene attack on Pd(II), which is essential for the oxidative carbocyclization. Furthermore, a highly selective palladium-catalyzed allenic C(sp3)-H bond oxidation of allenes in the absence of an assisting group was developed, which provides a novel and straightforward synthesis of [3]dendralene derivatives. For the oxidative systems, benzoquinone (BQ) and its derivatives are commonly used as oxidants or catalytic co-oxidants (electron transfer mediators, ETMs) together with molecular oxygen. A variety of transformations including carbocyclization, acetoxylation, arylation, carbonylation, borylation, beta-hydride elimination, alkynylation, alkoxylation, and olefination have been demonstrated to be compatible with this Pd(II)-based catalytic oxidative system. Recently, several challenging synthetic targets, such as cyclobutenes, seven-membered ring carbocycles, spirocyclic derivatives, functional cyclohexenes, and chiral cyclopentenone derivatives were obtained with high selectivity using these methods. The mechanisms of the reactions were mainly studied by kinetic isotope effects (KIEs) or DFT computations, which showed that in most cases the C(sp3)-H cleavage is the rate determining step (RDS) or partially RDS. This Account will describe our efforts toward the development of highly selective and atom-economic palladium(II) catalyzed oxidative transformation of allenes (including enallenes, dienallenes, bisallenes, allenynes, simple allenes, and allenols) with a focus on overcoming the selectivity problem during the reactions. PMID- 29792669 TI - Self-Assembling Glutamate-Functionalized Cyclodextrin Molecular Tube for Specific Enrichment of N-Linked Glycopeptides. AB - Cyclodextrin molecular tube (CDMT), a new comer of cyclodextrin family, possesses large and hydrophilic outer area and stable structure. Its development and applications remain highly desired, especially in the field of separation and enrichment. Herein, we developed a CDMT-based enrichment platform focusing on the specific capture of glycopeptides. To enhance the hydrophilicity of CDMT, it was functionalized with glutamate (glu). The prepared gluCDMT exhibited large hydrophilic surface, high stability, and good acidic/alkalic resistance. A solid monolithic support was employed to immobilize gluCDMT by a host-guest self assembly synthetic strategy, which did not occupy the surface hydrophilic sites. The gluCDMT-based monolith exhibited high binding capacity (~50 mg g-1), good ability to capture glycopeptides (23 HRP glycopeptides and 28 IgG glycopeptides), and high selectivity (horseradish peroxidase/bovine serum albumin = 1:10 000). Moreover, the developed platform was successfully applied to analyze glycopetides in acute myelogenous leukemia cell lysate and human serum samples. PMID- 29792668 TI - Out-of-Plane Ionic Conductivity Measurement Configuration for High-Throughput Experiments. AB - An approach for measuring conductivity of thin-film electrolytes in an out-of plane configuration, amenable to high-throughput experimentation, is presented. A comprehensive analysis of the geometric requirements for success is performed. Using samaria-doped ceria (Ce0.8Sm0.2O1.9, SDC) excellent agreement between bulk samples and thin films with continuous and patterned electrodes, 100-500 MUm in diameter, is demonstrated. Films were deposited on conductive Nb-doped SrTiO3, and conductivity was measured by AC impedance spectroscopy over the temperature range from ~200 to ~500 degrees C. The patterned electrode geometry, which encompassed an array of microdot metal electrodes for making top contact, enabled measurements at hundreds of positions on the film, implying the potential for measuring hundreds of composition in a single library. PMID- 29792670 TI - Biomarker-Based Metabolic Labeling for Redirected and Enhanced Immune Response. AB - Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Such an approach can be an alternative strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases. Herein we describe the development of a new strategy to selectively label targets with an antibody-recruiting moiety through its covalent and stable installation, complementing existing methods of employing reversible binding. This is achieved through selective delivery of 1,3,4- O-acetyl- N-azidoacetylmannosamine (Ac3ManNAz) to folate receptor overexpressing cells using an Ac3ManNAz-folate conjugate via a cleavable linker. As such, Ac3ManNAz is converted to cell surface glycan bearing an azido group, which serves as an anchor to introduce l-rhamnose (Rha), a hapten, via a click reaction with aza-dibenzocyclooctyne (DBCO)-Rha. We tested this method in several cell lines including KB, HEK-293, and MCF7 and were able to demonstrate the following: 1) Rha can be selectively installed to the folate receptor overexpressing cell surface and 2) the Rha installed on the target surface can recruit anti-rhamnose (anti-Rha) antibodies, leading to the destruction of target cells via complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP). PMID- 29792671 TI - The Chemoattractant Glorin Is Inactivated by Ester Cleavage during Early Multicellular Development of Polysphondylium pallidum. AB - Among the amoebozoan species capable of forming fruiting bodies, the dictyostelid social amoebae stand out since they form true multicellular organisms by means of single cell aggregation. Upon food depletion, cells migrate across gradients of extracellular signals initiated by cells in aggregation centers. The model species that is widely used to study multicellular development of social amoebae, Dictyostelium discoideum, uses cyclic adenosine monophosphate (cAMP) as a chemoattractant to coordinate aggregation. Molecular phylogeny studies suggested that social amoebae evolved in four major groups, of which groups 1 and 2 are paraphyletic to groups 3 and 4. During early development, intercellular communication with cAMP appears to be restricted to group 4 species. Cells of group 1 and 2 taxa do not respond chemotactically to extracellular cAMP and likely use a dipeptide chemoattractant known as glorin ( N-propionyl-gamma-L glutamyl-L-ornithin-delta-lactam-ethylester) to regulate aggregation. Directional migration of glorin-responsive cells requires the periodic breakdown of the chemoattractant. Here, we identified an extracellular enzymatic activity (glorinase) in the glorin-responsive group 2 taxon Polysphondylium pallidum leading to the inactivation of glorin. We determined the inactivation mechanism to proceed via hydrolytic ethyl ester cleavage of the gamma-glutamyl moiety of glorin. Synthetic glorinamide, in which the ethyl ester group was substituted by an ethyl amide group, had glorin-like biological activity but was resistant to degradation by glorinase. Our observations pave the way for future investigations toward an ancient eukaryotic chemotaxis system. PMID- 29792672 TI - Biosynthesis of Lincosamide Antibiotics: Reactions Associated with Degradation and Detoxification Pathways Play a Constructive Role. AB - Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function. Consequently, the interactions between living organisms and their environments serve as an engine that drives coevolution of natural products and their biological functions and ultimately programs the constant theme of small-molecule development in nature based on biosynthesis generality and specificity. Following this theme, we herein review the biosynthesis of lincosamide antibiotics and dissect the process through which nature creates an unusual eight-carbon aminosugar (lincosamide) and then functionalizes this common high-carbon chain-containing sugar core with diverse l proline derivatives and sulfur appendages to form individual members, including the clinically useful anti-infective agent lincomycin A and its naturally occurring analogues celesticetin and Bu-2545. The biosynthesis of lincosamide antibiotics is unique in that it results from an intersection of anabolic and catabolic chemistry. Many reactions that are usually involved in degradation and detoxification play a constructive role in biosynthetic processes. Formation of the trans-4-propyl-l-proline residue in lincomycin A biosynthesis requires an oxidation-associated degradation-like pathway composed of heme peroxidase catalyzed ortho-hydroxylation and non-heme 2,3-dioxygenase-catalyzed extradiol cleavage for l-tyrosine processing prior to the building-up process. Mycothiol (MSH) and ergothioneine (EGT), two small-molecule thiols that are known for their redox-relevant roles in protection against various endogenous and exogenous stresses, function through two unusual S-glycosylations to mediate an eight carbon aminosugar transfer, activation, and modification during the molecular assembly and tailoring processes in lincosamide antibiotic biosynthesis. Related intermediates include an MSH S-conjugate, mercapturic acid, and a thiomethyl product, which are reminiscent of intermediates found in thiol-mediated detoxification metabolism. In these biosynthetic pathways, "old" protein folds can result in "new" enzymatic activity, such as the DinB-2 fold protein for thiol exchange between EGT and MSH, the gamma-glutamyltranspeptidase homologue for C-C bond cleavage, and the pyridoxal-5'-phosphate-dependent enzyme for diverse S functionalization, generating interest in how nature develops remarkably diverse biochemical functions using a limited range of protein scaffolds. These findings highlight what we can learn from natural product biosynthesis, the recognition of its generality and specificity, and the natural theme of the development of bioactive small molecules, which enables the diversification process to advance and expand small-molecule functions. PMID- 29792673 TI - Recent Advances on Sodium-Oxygen Batteries: A Chemical Perspective. AB - Releasing greenhouse gases into the atmosphere because of widespread use of fossil fuels by humankind has resulted in raising the earth's temperature during the past few decades. Known as global warming, increasing the earth's temperature may in turn endanger civilization on the earth by starting a cycle of environmental changes including climate change and sea level rise. Therefore, replacing fossil fuels with more sustainable energy resources has been considered as one of the main strategies to tackle the global warming crisis. In this regard, energy saving devices are required to store the energy from sustainable resources like wind and solar when they are available and deliver them on demand. Moreover, developing plug-in electric vehicles (PEVs) as an alternative for internal combustion engines has been extensively pursued, since a major sector of fossil fuels is used for transportation purposes. However, currently available battery systems fail to meet the required demands for energy storage. Alkali metal-O2 battery systems demonstrate a promising prospect as a high-energy density solution regarding the increasing demand of mankind for energy storage. Combining a metallic negative electrode with a breathing oxygen electrode, a metal-O2 cell can be considered as a half battery/half fuel cell system. The negative electrode in the metal-O2 cells operates a conversion reaction rather than intercalation mechanism, which eliminates the need for a host lattice. In addition, the positive electrode material (O2) comes from the ambient air and hence is not stored in the battery. Therefore, the resultant battery systems exhibit the highest theoretical energy density, which is comparable to that of gasoline. Accordingly, an unprecedented amount of research activity was directed toward alkali metal-O2 batteries in the past decade in response to the need for high-energy storage technology in electric transportation. This extensive research surge has resulted in a rapid expansion of our knowledge about alkali metal-O2 batteries. The present Account summarizes the most recent findings over the underlying chemistry of all components in Na-O2 cells as one of the most efficient members of alkali metal-O2 family. PMID- 29792674 TI - Partial Intrinsic Disorder Governs the Dengue Capsid Protein Conformational Ensemble. AB - The 11 kDa, positively charged dengue capsid protein (C protein) exists stably as a homodimer and colocalizes with the viral genome within mature viral particles. Its core is composed of four alpha helices encompassing a small hydrophobic patch that may interact with lipids, but approximately 20% of the protein at the N terminus is intrinsically disordered, making it challenging to elucidate its conformational landscape. Here, we combine small-angle X-ray scattering (SAXS), amide hydrogen-deuterium exchange mass spectrometry (HDXMS), and atomic resolution molecular dynamics (MD) simulations to probe the dynamics of dengue C proteins. We show that the use of MD force fields (FFs) optimized for intrinsically disordered proteins (IDPs) is necessary to capture their conformational landscape and validate the computationally generated ensembles with reference to SAXS and HDXMS data. Representative ensembles of the C protein dimer are characterized by alternating, clamp-like exposure and occlusion of the internal hydrophobic patch, as well as by residual helical structure at the disordered N-terminus previously identified as a potential source of autoinhibition. Such dynamics are likely to determine the multifunctionality of the C protein during the flavivirus life cycle and hence impact the design of novel antiviral compounds. PMID- 29792675 TI - Electron-Phonon Coupling and Resonant Relaxation from 1D and 1P States in PbS Quantum Dots. AB - Observations of the hot-phonon bottleneck, which is predicted to slow the rate of hot carrier cooling in quantum confined nanocrystals, have been limited to date for reasons that are not fully understood. We used time-resolved infrared spectroscopy to directly measure higher energy intraband transitions in PbS colloidal quantum dots. Direct measurements of these intraband transitions permitted detailed analysis of the electronic overlap of the quantum confined states that may influence their relaxation processes. In smaller PbS nanocrystals, where the hot-phonon bottleneck is expected to be most pronounced, we found that relaxation of parity selection rules combined with stronger electron-phonon coupling led to greater spectral overlap of transitions among the quantum confined states. This created pathways for fast energy transfer and relaxation that may bypass the predicted hot-phonon bottleneck. In contrast, larger, but still quantum confined nanocrystals did not exhibit such relaxation of the parity selection rules and possessed narrower intraband states. These observations were consistent with slower relaxation dynamics that have been measured in larger quantum confined systems. These findings indicated that, at small radii, electron-phonon interactions overcome the advantageous increase in energetic separation of the electronic states for PbS quantum dots. Selection of appropriately sized quantum dots, which minimize spectral broadening due to electron-phonon interactions while maximizing electronic state separation, is necessary to observe the hot-phonon bottleneck. Such optimization may provide a framework for achieving efficient hot carrier collection and multiple exciton generation. PMID- 29792676 TI - Dramatic Increase in Polymer Glass Transition Temperature under Extreme Nanoconfinement in Weakly Interacting Nanoparticle Films. AB - Properties of polymers in polymer nanocomposites and nanopores have been shown to deviate from their respective bulk properties due to physical confinement as well as polymer-particle interfacial interactions. However, separating the confinement effects from the interfacial effects under extreme nanoconfinement is experimentally challenging. Capillary rise infiltration enables polymer infiltration into nanoparticle (NP) packings, thereby confining polymers within extremely small pores and dramatically increasing the interfacial area, providing a good system to systematically distinguish the role of each effect on polymer properties. In this study, we investigate the effect of spatial confinement on the glass transition temperature ( Tg) of polystyrene (PS) infiltrated into SiO2 NP films. The degree of confinement is tuned by varying the molecular weight of polymers, the size of NPs (diameters between 11 and 100 nm, producing 3-30 nm average pore sizes), and the fill-fraction of PS in the NP films. We show that in these dense NP packings the Tg of confined PS, which interacts weakly with SiO2 NPs, significantly increases with decreasing pore size such that for the two molecular weights of PS studied the Tg increases by up to 50 K in 11 nm NP packings, while Tg is close to the bulk Tg in 100 nm NP packings. Interestingly, as the fill-fraction of PS is decreased, resulting in the accumulation of the polymer in the contacts between nanoparticles, hence an increased specific interfacial area, the Tg further increases relative to the fully filled films by another 5-8 K, indicating the strong role of geometrical confinement as opposed to the interfacial effects on the measured Tg values. PMID- 29792677 TI - Ultra-Low-Power Smart Electronic Nose System Based on Three-Dimensional Tin Oxide Nanotube Arrays. AB - In this work, we present a high-performance smart electronic nose (E-nose) system consisting of a multiplexed tin oxide (SnO2) nanotube sensor array, read-out circuit, wireless data transmission unit, mobile phone receiver, and data processing application (App). Using the designed nanotube sensor device structure in conjunction with multiple electrode materials, high-sensitivity gas detection and discrimination have been achieved at room temperature, enabling a 1000 times reduction of the sensor's power consumption as compared to a conventional device using thin film SnO2. The experimental results demonstrate that the developed E nose can identify indoor target gases using a simple vector-matching gas recognition algorithm. In addition, the fabricated E-nose has achieved state-of the-art sensitivity for H2 and benzene detection at room temperature with metal oxide sensors. Such a smart E-nose system can address the imperative needs for distributed environmental monitoring in smart homes, smart buildings, and smart cities. PMID- 29792678 TI - Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait Conjugated Peptide to Reactive Modifier. AB - A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display. To obtain the targeted covalent binder, the bait in the selected consensus peptide was altered into a reactive warhead possessing a sulfonyl fluoride. The reaction efficiency and site/position specificity of the covalent conjugation between the binder and the target protein were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and rationalized by a protein-ligand docking simulation. PMID- 29792679 TI - A Nanozyme- and Ambient Light-Based Smartphone Platform for Simultaneous Detection of Dual Biomarkers from Exposure to Organophosphorus Pesticides. AB - A transparent, lateral-flow test strip coupled with a smartphone-based ambient light sensor was first proposed for detecting enzymatic inhibition and phosphorylation. The principle of the platform is based on the simultaneous measurement of the total amount of the enzyme and enzyme activity to biomonitor exposure to organophosphorus (OP) pesticides. In this study, butyrylcholinesterase (BChE) was adopted as the model enzyme and ethyl paraoxon was chosen as an analyte representing OP pesticides. The total amount of BChE was quantified by a sensitive colorimetric signal originating from a sandwich immunochromatographic assay utilizing PtPd nanoparticles as a colorimetric probe, which exhibited excellent catalytic activity for phenols. In the sandwich immunoassay, only one antibody against BChE was simultaneously utilized as the recognition antibody and the labeling antibody due to the tetrameric structure of native BChE. The BChE activity was estimated by another colorimetric signal using the Ellman assay. Both colorimetric signals on two separated test strips were detected by the smartphone-based ambient light sensor. The proposed sensor operated with an LED in a 3D-printed substrate, which emitted excitation light and transmitted it through a transparent, lateral-flow test strip. With the increase in the colorimetric signal in the test line of the test strip, the intensity of the transmitted light decreased. The smartphone-based sensor showed excellent linear responses for assaying the total amount of BChE and active BChE ranging from 0.05 to 6.4 nM and from 0.1 to 6.4 nM, respectively. A high portability and low detection limit were simultaneously realized in the common smartphone-based device. This low-cost, portable, easy-operation, and sensitive immunoassay strategy shows great potential for online detection of OP exposure and monitoring other disease biomarkers. PMID- 29792681 TI - Protein-Based Electronic Skin Akin to Biological Tissues. AB - Human skin provides an interface that transduces external stimuli into electrical signals for communication with the brain. There has been considerable effort to produce soft, flexible, and stretchable electronic skin (E-skin) devices. However, common polymers cannot imitate human skin perfectly due to their poor biocompatibility, biofunctionality, and permeability to many chemicals and biomolecules. Herein, we report on highly flexible, stretchable, conformal, molecule-permeable, and skin-adhering E-skins that combine a metallic nanowire (NW) network and silk protein hydrogel. The silk protein hydrogels offer high stretchability and stability under hydration through the addition of Ca2+ ions and glycerol. The NW electrodes exhibit stable operation when subjected to large deformations and hydration. Meanwhile, the hydrogel window provides water and biomolecules to the electrodes (communication between the environment and the electrode). These favorable characteristics allow the E-skin to be capable of sensing strain, electrochemical, and electrophysiological signals. PMID- 29792680 TI - Quantification of Cellular Folate Species by LC-MS after Stabilization by Derivatization. AB - Folate cofactors play a key role in one-carbon metabolism. Analysis of individual folate species is hampered by the low chemical stability and high interconvertibility of folates, which can lead to severe experimental bias. Here, we present a complete workflow that employs simultaneous extraction and stabilization of folates by derivatization. We perform reductive methylation employing stable isotope labeled reagents to retain information on the position and redox state of one-carbon units as well as the redox state of the pteridine ring. The derivatives are analyzed by a targeted LC(HILIC)-MS/MS method without the need for deconjugation, thereby also preserving the glutamation state of folates. The presented method does not only improve analyte coverage and sensitivity as compared to other published methods, it also greatly simplifies sample handling and storage. Finally, we report differences in the response of bacterial and mammalian systems to pharmacological inhibition of dihydrofolate reductase. PMID- 29792682 TI - Calix[4]arene Based Redox Sensitive Molecular Probe for SERS Guided Recognition of Labile Iron Pool in Tumor Cells. AB - Targeting the intracellular "labile" iron pool is turned as a key modulator for cancer progression since the former is responsible for several pathological processes in tumor cells. Herein, we report a nonfluorescent calix[4]arene based triazole appended molecular probe (PTBC) for redox-specific detection of Fe3+ under physiological condition by UV-vis, FT-IR, 1H NMR, HR-MS spectroscopies, ITC, and the binding strategy between Calix[4]arene and Fe3+ was modeled by DFT calculations. As a new insight PTBC probe showed significant Raman fingerprint through surface enhanced Raman scattering (SERS) modality revealing the ultrasensitive detection of Fe3+ with a LOD of 2 nM. Interestingly, intracellular "iron pool" has been recognized in human lung adenocarcinoma cells (A549) by the PTBC illustrating the distinct Raman mapping. Finally, PTBC imparted cytotoxicity via reactive oxygen species (ROS) generation in cellular milieu signifies its capability as a theranostic molecular probe. PMID- 29792683 TI - Top-Down Deep Sequencing of Ubiquitin Using Two-Dimensional Mass Spectrometry. AB - Two-dimensional mass spectrometry (2DMS) allows data independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors without isolation prior to fragmentation. Developments in computer capabilities and implementations in Fourier transform ion cyclotron resonance (FTICR) MS over the past decade have allowed the technique to become a useful analytical tool for bottom-up proteomics (BUP) and, more recently, in top-down protein analysis (TDP). In this work, a new method of TDP is developed using 2D FTICR MS, called MS/2D FTICR MS or MS/2DMS. In MS/2DMS, an entire protein is initially fragmented in a hexapole collision cell, e.g., with collisionally activated dissociation (CAD). The primary fragments are then sent to the ICR cell, where 2DMS is performed with infrared multiphoton dissociation (IRMPD) or electron-capture dissociation (ECD). The resulting 2D mass spectra retain information equivalent to a set of TDP MS3 experiments on the selected protein. Up to n - 1 fragmentation steps can be added to the process, as long as an ion of interest can be unambiguously fragmented before the ICR cell, leading to an MS n/2DMS experiment whose output is a 2D mass spectrum retaining information equivalent to MS n. MS/2DMS and MS/MS/2DMS are used in this work for the structural analysis of ubiquitin (Ubi), noting several unique features which aid fragment identification. The use of CAD-MS/IRMPD-2DMS, CAD-MS/ECD-2DMS, and MS2/2DMS using, respectively, in-source dissociation (ISD), CAD, and ECD-2DMS led to 97% cleavage coverage for Ubi. PMID- 29792684 TI - Label-Free Optical Marker for Red-Blood-Cell Phenotyping of Inherited Anemias. AB - The gold-standard methods for anemia diagnosis are complete blood counts and peripheral-smear observations. However, these do not allow for a complete differential diagnosis as that requires biochemical assays, which are label dependent techniques. On the other hand, recent studies focus on label-free quantitative phase imaging (QPI) of blood samples to investigate blood diseases by using video-based morphological methods. However, when sick cells are very similar to healthy ones in terms of morphometric features, identification of a blood disease becomes challenging even with QPI. Here, we introduce a label-free optical marker (LOM) to detect red-blood-cell (RBC) phenotypes, demonstrating that a single set of all-optical parameters can clearly identify a signature directly related to an erythrocyte disease through modeling each RBC as a biological lens. We tested this novel biophotonic analysis by proving that several inherited anemias, such as iron-deficiency anemia, thalassemia, hereditary spherocytosis, and congenital dyserythropoietic anemia, can be identified and sorted, thus opening a novel route for blood diagnosis on a completely different concept based on LOMs. PMID- 29792685 TI - Vertical Ultrafiltration-Facilitated DNA Digestion for Rapid and Sensitive UHPLC MS/MS Detection of DNA Modifications. AB - LC-MS/MS technologies provide important and powerful analytical tools for chemical structure-dependent identification and quantification of epigenetically crucial DNA modifications. To perform LC-MS/MS analysis, it is better to convert DNA to 2'-deoxynucleosides through enzymatic digestion. Here, we observed that inorganic cations Na+ and K+ and phosphate buffers, which were often found in various DNA solutions, significantly inhibited DNA digestion as catalyzed by typical set of DNase I, snake venom phosphodiesterase, and calf intestine alkaline phosphatase, leading to poor or varying performance on UHPLC-MS/MS analysis. We then developed an efficient and unique vertical-ultrafiltration approach, enabling us to remove these inorganic salts without DNA loss. Consequently, the removal of inorganic salts by ultrafiltration facilitated the followed DNA digestion and thus enhanced the final UHPLC-MS/MS detection. Benefiting from the developed vertical-ultrafiltration approach, it is also feasible to integrate the desalting step with the other two steps of DNA digestion and protein removal. By investigating the time course of DNA digestion, we observed a differential release rate of 2'-deoxycytidine and 5-methyl-2' deoxycytidine causing a measurement bias on the methylation frequency. We further exploited Mg2+ to eliminate this bias by stimulating DNase set-based DNA digestion. These innovative approaches enable us to perform rapid, sensitive, and robust UHPLC-MS/MS analysis of methylated DNA 2'-deoxycytidine, demethylation intermediates, and probably other DNA modifications. PMID- 29792686 TI - High-Throughput Screens for cis-Acting RNA Sequence Elements That Promote Nuclear Retention. PMID- 29792687 TI - Comobility of GABARAP and Phosphatidylinositol 4-Kinase 2A on Cytoplasmic Vesicles. AB - We previously reported that recruitment of the type IIA phosphatidylinositol 4 kinase (PI4K2A) to autophagosomes by GABARAP, a member of the Atg8 family of autophagy-related proteins, is important for autophagosome-lysosome fusion. Because both PI4K2A and GABARAP have also been implicated in the intracellular trafficking of plasma membrane receptors in the secretory/endocytic pathway, we characterized their interaction in cells under nonautophagic conditions. Fluorescence fluctuation spectroscopy measurements revealed that GABARAP exists predominantly as a cytosolic monomer in live cells, but is recruited to small cytoplasmic vesicles upon overexpression of PI4K2A. C-Terminal lipidation of GABARAP, which is essential for its autophagic activities, is not necessary for its recruitment to these PI4K2A-containing transport vesicles. However, a GABARAP truncation mutant lacking C-terminal residues 103-117 fails to bind to PI4K2A, is not recruited to cytoplasmic vesicles, and does not codistribute with PI4K2A on subcellular organelles. These observations suggest that the PI4K2A-GABARAP interaction plays a role in membrane trafficking both under autophagic and nonautophagic conditions. PMID- 29792688 TI - Rhodium Complexes Bearing PAlP Pincer Ligands. AB - We report rhodium complexes bearing PAlP pincer ligands with an X-type aluminyl moiety. IR spectroscopy and single-crystal X-ray diffraction analysis of a carbonyl complex exhibit the considerable sigma-donating ability of the aluminyl ligand, whose Lewis acidity is confirmed through coordination of pyridine to the aluminum center. The X-type PAlP-Rh complexes catalyze C2-selective monoalkylation of pyridine with alkenes. PMID- 29792689 TI - Selectivity within a Family of Bacterial Phosphothreonine Lyases. AB - Phosphothreonine lyases are bacterial effector proteins secreted into host cells to facilitate the infection process. This enzyme family catalyzes an irreversible elimination reaction that converts phosphothreonine or phosphoserine to dehydrobutyrine or dehydroalanine, respectively. Herein, we report a study of substrate selectivity for each of the four known phosphothreonine lyases. This was accomplished using a combination of mass spectrometry and enzyme kinetics assays for a series of phosphorylated peptides derived from the mitogen-activated protein kinase (MAPK) activation loop. These studies provide the first experimental evidence that VirA, a putative phosphothreonine lyase identified through homology, is indeed capable of catalyzing phosphate elimination. These studies further demonstrate that OspF is the most promiscuous phosphothreonine lyase, whereas SpvC is the most specific for the MAPK activation loop. Our studies reveal that phospholyases are dramatically more efficient at catalyzing elimination from phosphothreonine than from phosphoserine. Together, our data suggest that each enzyme likely has preferred substrates, either within the MAPK family or beyond. Fully understanding the extent of selectivity is key to understanding the impact of phosphothreonine lyases during bacterial infection and to exploiting their unique chemistry for a range of applications. PMID- 29792690 TI - A General Method To Increase Stokes Shift by Introducing Alternating Vibronic Structures. AB - Fluorescent dyes have enabled much progress in the broad range of biomedical fields. However, many commercially available dyes suffer from small Stokes shifts, resulting in poor signal-to-noise ratio and self-quenching on current microscope configurations. In this work, we have developed a general method to significantly increase the Stokes shifts of common fluorophores. By simply appending a 1,4-diethyl-decahydro-quinoxaline (DQ) moiety onto the conjugated structure, we introduced a vibronic backbone that could facilely expand the Stokes shifts, emission wavelength, and photostability of 11 different fluorophores by more than 3-fold. This generalizable method could significantly improve the imaging efficiency of commercial fluorophores. As a demonstration, we showed that the DQ derivative of hemicyanine generated 5-fold signal in mouse models over indocyanine green. Furthermore, the DQ-modified fluorophores could pair with their parent molecules to conduct one-excitation, multiple emission imaging, allowing us to study the cell behavior more robustly. This approach shows promise in generating dyes suitable for super-resolution microscopy and second window near-infrared imaging. PMID- 29792691 TI - The Role of Small Nanoparticles on the Formation of Hot Spots under Microwave Assisted Hydrothermal Heating. AB - Herein, we report a detailed study of microwave-matter interaction focused on the role of small nanoparticles and the effects on microwave thermal heating. We have used a model reaction (degradation of methylene blue) to study the influence of temperature, size, and catalytic properties of the nanoparticles in the potential formation of hot spots. Total mineralization was achieved after 3 h microwave heating at 200 degrees C in the presence of 2 nm TiO2 nanoparticles (92% calculated TOC decay), but the reaction resulted in a mixture of intermediates (52% TOC decay) in the absence of TiO2. The effect of temperature was evaluated by carrying out the reaction at 120 degrees C, and the results were similar to those obtained in the absence of TiO2, but with lower TOC removal efficiencies (12-14%). For comparison, the degradation of MB was also followed using (noncatalytic) SiO2 and MnO2 nanoparticles of comparable size. Differences in the degradation efficiency may be ascribed to the formation of hot spots at the particles surface, as a result of large heat accumulation liable to provide enough energy to the system to accomplish C-C bond break and to achieve total mineralization. PMID- 29792692 TI - Small Molecule Targeted Recruitment of a Nuclease to RNA. AB - The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion. Silencing miR-96 derepressed pro-apoptotic FOXO1 transcription factor, triggering apoptosis in breast cancer, but not healthy breast, cells. These results demonstrate that small molecules can be programmed to selectively cleave RNA via nuclease recruitment and has broad implications. PMID- 29792693 TI - A Titanium Oxo Cluster Model Study of Synergistic Effect of Co-coordinated Dye Ligands on Photocurrent Responses. AB - The use of multiple sensitizers in dye sensitized solar cells has been attractive as a promising way to achieve highly efficient photovoltaic performance. However, except for the complementary absorption, synergistic effects among the dye components have not been well understood. Herein, using ferrocene-1-carboxylate (FcCO2) and catechol (Cat) as dye ligands, two titanium oxo clusters (TOCs), [Ti3O(OiPr)6(Cat)(FcCO2)2] (1) and [Ti7O4(OiPr)8(Cat)5(FcCO2)2] (2), were synthesized and structurally characterized. Another TOC, [Ti7O3(OiPr)12(Cat)4( o BDC)] (3) ( o-BDC = o-benzene dicarboxylate), was also prepared as a contrast. Electronic spectra and theoretical calculations showed that charge transfer occurs from ligands FcCO2 and Cat to the TiO cluster core and the contribution of redox active FcCO2 is greater than that of Cat. Using the clusters as TiO-dye pre anchored precursors, multi-dye sensitized TiO2 electrodes were prepared. Although the two dyes FcCO2 and Cat do not complement each other in spectra, a synergistic effect on the enhancement of photocurrent responses was found and discussed in view of the inter-dyes electron communication. PMID- 29792694 TI - Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones. AB - While the central role of locus-specific acetylation of histone proteins in eukaryotic gene expression is well established, the availability of designer tools to regulate acetylation at particular nucleosome sites remains limited. Here, we develop a unique strategy to introduce acetylation by constructing a bifunctional molecule designated Bi-PIP. Bi-PIP has a P300/CBP-selective bromodomain inhibitor (Bi) as a P300/CBP recruiter and a pyrrole-imidazole polyamide (PIP) as a sequence-selective DNA binder. Biochemical assays verified that Bi-PIPs recruit P300 to the nucleosomes having their target DNA sequences and extensively accelerate acetylation. Bi-PIPs also activated transcription of genes that have corresponding cognate DNA sequences inside living cells. Our results demonstrate that Bi-PIPs could act as a synthetic programmable histone code of acetylation, which emulates the bromodomain-mediated natural propagation system of histone acetylation to activate gene expression in a sequence-selective manner. PMID- 29792695 TI - Bond Dissociation Energies of Metallo-supramolecular Building Blocks: Insight from Fragmentation of Selectively Self-Assembled Heterometallic Metallo supramolecular Aggregates. AB - A series of selectively self-assembled metallo-supramolecular square-like macrocycles with unsymmetric ditopic linkers and two different types of metal corners, i.e., {Pd(eta3-2-Me-C3H4)} and {M(dppp)} with dppp = 1,3 bis(diphenylphosphino)propane and M = Pd2+ or Pt2+, have been studied in the gas phase using collision-induced dissociation. The aggregates show distinct fragmentation patterns determined by ligand length, i.e, aggregate size, and type of metal corner. Information on relative binding strength can be deduced. This is of particular interest for (methylallyl)Pd as a relatively new building block in metallo-supramolecular chemistry. The phosphane end of the unsymmetric ligand connected to (eta3-2-Me-C3H4)Pd is bound significantly stronger than its pyridine end to (dppp)Pt and (dppp)Pd. These results are corroborated by DFT calculations. PMID- 29792697 TI - Association of Type 2 Diabetes with Submicron Titanium Dioxide Crystals in the Pancreas. AB - Pigment-grade titanium dioxide (TiO2) of 200-300 nm particle diameter is the most widely used submicron-sized particle material. Inhaled and ingested TiO2 particles enter the bloodstream, are phagocytized by macrophages and neutrophils, are inflammatory, and activate the NLRP3 inflammasome. In this pilot study of 11 pancreatic specimens, 8 of the type 2 diabetic pancreas and 3 of the nondiabetic pancreas, we show that particles comprising 110 +/- 70 nm average diameter TiO2 monocrystals abound in the type 2 diabetic pancreas, but not in the nondiabetic pancreas. In the type 2 diabetic pancreas, the count of the crystals is as high as 108-109 per gram. PMID- 29792698 TI - Site-Selective Switching Strategies to Functionalize Polyazines. AB - Many drug fragments and therapeutic compounds contain multiple pyridines and diazines. Developing site-selective reactions where specific C-H bonds can be transformed in polyazine structures would enable rapid access to valuable derivatives. We present a study that addresses this challenge by selectively installing a phosphonium ion as a versatile functional handle. Inherent factors that control site-selectivity are described along with mechanistically driven approaches for site-selective switching, where the C-+PPh3 group can be predictably installed at other positions in the polyazine system. Simple protocols, readily available reagents, and application to complex drug-like molecules make this approach appealing to medicinal chemists. PMID- 29792696 TI - Biochemical and Structural Characterization of a Schiff Base in the Radical Mediated Biosynthesis of 4-Demethylwyosine by TYW1. AB - TYW1 is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the condensation of pyruvate and N-methylguanosine to form the posttranscriptional modification, 4-demethylwyosine, in situ on transfer RNA (tRNA). Two mechanisms have been proposed for this transformation, with one of the possible mechanisms invoking a Schiff base intermediate formed between a conserved lysine residue and pyruvate. Utilizing a combination of mass spectrometry and X-ray crystallography, we have obtained evidence to support the formation of a Schiff base lysine adduct in TYW1. When 13C labeled pyruvate is used, the mass shift of the adduct matches that of the labeled pyruvate, indicating that pyruvate is the source of the adduct. Furthermore, a crystal structure of TYW1 provides visualization of the Schiff base lysine-pyruvate adduct, which is positioned directly adjacent to the auxiliary [4Fe-4S] cluster. The adduct coordinates the unique iron of the auxiliary cluster through the lysine nitrogen and a carboxylate oxygen, reminiscent of how the radical SAM [4Fe-4S] cluster is coordinated by SAM. The structure provides insight into the binding site for tRNA and further suggests how radical SAM chemistry can be combined with Schiff base chemistry for RNA modification. PMID- 29792700 TI - Energy Landscapes of Mini-Dumbbell DNA Octanucleotides. AB - Single-stranded DNA structures play a significant role in biological systems, in particular during replication, translation, and DNA repair. Tracts of simple repetitive DNA are associated with slipped-strand mispairing, which can lead to genetic diseases. Recent NMR studies of TTTA and CCTG repeats have shown that these sequences form mini-dumbbells (MDBs), leading to frameshift mutations. Here we explore the energy landscapes of (CCTG)2 and (TTTA)2, which are currently the smallest known molecules to form MDBs. While (CCTG)2 MDBs are stable, (TTTA)2 exhibits numerous other structures with lower energies. A key factor identified in the stabilization of MDB structures is the bonding strength between residues 1 and 4, and 5 and 8. PMID- 29792699 TI - Water-Soluble Ruthenium(II) Carbonyls with 1,3,5-Triaza-7-phosphoadamantane. AB - As a continuation of our strategy for preparing new Ru(II) precursors with improved water solubility through the introduction of highly water-soluble 1,3,5 triaza-7-phosphoadamantane (PTA) supporting ligands in the coordination sphere, in this work, we address the largely unexplored preparation of Ru(II)-PTA carbonyls. Two complementary synthetic approaches were used: (1) the treatment of a series of neutral Ru(II)-CO-dmso compounds of general formula RuCl2(CO) n(dmso)4- n ( n = 1-3, 1-5) with PTA; (2) the reaction of Ru(II)-PTA complexes with CO. Through the first approach, we obtained and fully characterized seven novel neutral compounds bearing from one to three PTA ligands per Ru atom, namely, the four monocarbonyls, cis, cis, trans-RuCl2(CO)(dmso-S)(PTA)2 (6), trans-RuCl2(CO)(PTA)3 (7), cis, mer-RuCl2(CO)(PTA)3 (8), and trans, trans, trans RuCl2(CO)(OH2)(PTA)2 (10), and the three dicarbonyls, trans, trans, trans RuCl2(CO)2(PTA)2 (11), [RuCl2(CO)2(PTA)]2 (12), and cis, cis, trans RuCl2(CO)2(PTA)2 (13). The less stable, and thus more elusive, species fac RuCl2(CO)(PTA)3 (9) and cis, cis, cis-RuCl2(CO)2(PTA)2 (14) were also unambiguously identified but could not be obtained in pure form and fully characterized. The complementary synthetic approach, that involved the treatment of the trans- and cis-RuCl2(PTA)4 (15, 16) isomers with CO, afforded only one new Ru(II)-PTA carbonyl, the cationic species cis-[RuCl(CO)(PTA)4]Cl (17). In general, the choice of the solvent was very relevant for obtaining the products with high yield and purity. We were unable to isolate Ru(II)-PTA compounds with more than two carbonyls. The thermodynamically preferred species have CO trans to Cl and two mutually trans PTAs, and only in the dinuclear compound 12 there is a single PTA per Ru atom. Compounds 7 and 17 feature the unprecedented trans {Ru(CO)(PTA)} fragment. The X-ray structures of cis, cis, cis-RuCl2(CO)2(dmso)2 (3), 6-8, 10, 11, 13, and 17 are also reported. All compounds are new, are air stable, and show a good solubility in water ( S from 10 to 165 g.L-1) and, most often, also in chloroform. PMID- 29792701 TI - Spatial and Temporal Variability in Emissions of Fluorinated Gases from a California Landfill. AB - Emissions of twelve (hydro)chlorofluorocarbons (F-gases) and methane were quantified using large-scale static chambers as a function of cover type (daily, intermediate, final) and seasonal variation (wet, dry) at a California landfill. The majority of the F-gas fluxes was positive and varied over 7 orders of magnitude across the cover types in a given season (wet: 10-8 to 10-1 g/m2-day; dry: 10-9 to 10-2 g/m2-day). The highest fluxes were from active filling areas with thin, coarse-grained daily covers, whereas the lowest fluxes were from the thick, fine-grained final cover. Historical F-gas replacement trends, waste age, and cover soil geotechnical properties affected flux with significantly lower F gas fluxes than methane flux (10-4 to 10+1 g/m2-day). Both flux and variability of flux decreased with the order: daily to intermediate to final covers; coarser to finer cover materials; low to high fines content cover soils; high to low degree of saturation cover soils; and thin to thick covers. Cover-specific F-gas fluxes were approximately one order of magnitude higher in the wet than dry season, due to combined effects of comparatively high saturations, high void ratios, and low temperatures. Emissions were primarily controlled by type and relative areal extent of cover materials and secondarily by season. PMID- 29792702 TI - Peniisocoumarins A-J: Isocoumarins from Penicillium commune QQF-3, an Endophytic Fungus of the Mangrove Plant Kandelia candel. AB - Ten new isocoumarins, named peniisocoumarins A-J (1-9 and 11), along with three known analogues (10, 12, and 13) were obtained from the fermentation of an endophytic fungus, Penicillium commune QQF-3, which was isolated from a fresh fruit of the mangrove plant Kandelia candel. Their structures were elucidated through extensive spectroscopic analysis. The absolute configurations of 1-7 were determined by single-crystal X-ray diffraction and modified Mosher's method, and those of 8, 9, and 11 were assigned on the basis of experimental and calculated electronic circular dichroism data. Compounds 1 and 2 were unusual dimeric isocoumarins with a symmetric four-membered core. These isolated compounds (1-13) were evaluated for their cytotoxicity and enzyme inhibitory activities against alpha-glucosidase and Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB). Among them, compounds 3, 7, 9, and 11 exhibited potent inhibitory effects against alpha-glucosidase with IC50 values ranging from 38.1 to 78.1 MUM, and compound 7 was found to inhibit MptpB with an IC50 value of 20.7 MUM. PMID- 29792703 TI - Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2. AB - Inhibition of androgen biosynthesis is clinically effective for treating androgen responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects. PMID- 29792704 TI - Double Hydrogen-Atom Exchange Reactions of HX (X = F, Cl, Br, I) with HO2. AB - A novel double hydrogen atom exchange process, HX + H'O2 -> H'X + HO2 for the halogen series X = F, Cl, Br, and I, is identified using theoretical methods. These concerted reactions are mediated through a stabilized five-membered planar ring transition state structure. The transition state barrier for the double exchange process is found to be significantly lower than that for the abstraction reaction of a single hydrogen atom. Density functional theory employing the M11 exchange functional is used to compute parameters of the potential energy surface and the rate coefficients are obtained using transition state theory with small curvature tunneling. For low temperatures, the exchange reaction proceeds at a rate several orders of magnitude faster than the abstraction channel, which is also calculated. The exchange process may be observed using isotope scrambling reactions; such reactions may contribute to observed isotope abundances in the atmosphere. The rate coefficients for the isotopically labeled reactions are computed. It is found that the trends in reactivity within the series of halogen reactions can be quantitatively understood using the degree of electron delocalization at the transition state. The barriers are found to fall as the electronegativity of the halogen atom decreases. PMID- 29792705 TI - Total Synthesis of Boletopsin 11 Enabled by Directed ortho-C(sp2)-H Arylation. AB - A nine-step synthesis of boletopsin 11 (1), a bioactive fungal natural product, is disclosed. Key features include a one-pot [O]-oxa-Michael cascade to establish the polyoxygenated dibenzofuran core followed by a Pd-catalyzed directed ortho C(sp2)-H arylation to complete the fully functionalized carbon skeleton. Exploration of the latter transformation led to the discovery of an unexpected tandem ortho-C(sp2)-H arylation event, and the scope of the directed ortho-C(sp2) H reaction was further investigated with coupling partners varying in stereoelectronic properties. PMID- 29792706 TI - Adaptable Detection Strategies in Membrane-Based Immunoassays: Calibration-Free Quantitation with Surface-Enhanced Raman Scattering Readout. AB - This paper presents a method for immunometric biomarker quantitation that uses standard flow-through assay reagents and obviates the need for constructing a calibration curve. The approach relies on a nitrocellulose immunoassay substrate with multiple physical addresses for analyte capture, each modified with different amounts of an analyte-specific capture antibody. As such, each address generates a distinctly different readout signal that is proportional to the analyte concentration in the sample. To establish the feasibility of this concept, equations derived from antibody-antigen binding equilibrium were first applied in modeling experiments. Next, nitrocellulose membranes with multiple capture antibody addresses were fabricated for detection of a model analyte, human Immunoglobulin G (hIgG), by a heterogeneous sandwich immunoassay using antibody-modified gold nanoparticles (AuNPs) as the immunolabel. Counting the number of colored capture addresses visible to the unassisted eye enabled semiquantitative hIgG determination. We then demonstrated that, by leveraging the localized surface plasmon resonance of the AuNPs, surface-enhanced Raman spectroscopy (SERS) can be used for quantitative readout. By comparing the SERS signal intensities from each capture address with values predicted using immunoassay equilibrium theory, the concentration of hIgG can be determined (~30% average absolute deviation) without reference to a calibration curve. This work also demonstrates the ability to manipulate the dynamic range of the assay over ~4 orders of magnitude (from 2 ng mL-1 to 10 MUg mL-1). The potential prospects in applying this concept to point-of-need diagnostics are also discussed. PMID- 29792707 TI - Nanoscale Conductive Filament with Alternating Rectification as an Artificial Synapse Building Block. AB - A popular approach for resistive memory (RRAM)-based hardware implementation of neural networks utilizes one (or two) device that functions as an analog synapse in a crossbar structure of perpendicular pre- and postsynaptic neurons. An ideal fully automated, large-scale artificial neural network, which matches a biologic counterpart (in terms of density and energy consumption), thus requires nanosized, extremely low power devices with a wide dynamic range and multilevel functionality. Unfortunately the trade-off between these traits proves to be a serious obstacle in the realization of brain-inspired computing platforms yet to be overcome. This study demonstrates an alternative manner for the implementation of artificial synapses in which the local stoichiometry of metal oxide materials is delicately manipulated to form a single nanoscale conductive filament that may be used as a synaptic gap building block in an equivalent manner to the functionality of a single connexon (a signaling pore between synapses) with dynamic rectification direction. The structure, of a few nanometers in size, is based on the formation of defect states and shows current rectification properties that can be consecutively flipped to a forward or reverse direction to create either an excitatory or inhibitory (positive or negative) weight parameter. Alternatively, a plurality of these artificial connexons may be used to create a synthetic rectifying synaptic gap junction. In addition, the junction plasticity may be altered in a differential digital scheme (opposed to conventional analog RRAM conductivity manipulation) by changing the ratio of forward to reverse rectifying connexons. PMID- 29792708 TI - Nonalcoholic Fatty Liver Disease and Diabetes Are Associated with Decreased CYP3A4 Protein Expression and Activity in Human Liver. AB - Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease in the Western population. We investigated the association of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus on CYP3A4 activity in human liver tissue from brain dead donors ( n = 74). Histopathologically graded livers were grouped into normal ( n = 24), nonalcoholic fatty liver (NAFL, n = 26), and nonalcoholic steatohepatitis (NASH, n = 24) categories. The rate of conversion of midazolam to its 1-hydroxy metabolite was used to assess in vitro CYP3A4 activity in human liver microsomes (HLM). A proteomics approach was utilized to quantify the protein expression of CYP3A4 and related enzymes. Moreover, a physiologically based pharmacokinetic (PBPK) model was developed to allow prediction of midazolam concentration in NAFL and NASH livers. CYP3A4 activity in NAFL and NASH was 1.9- and 3.1-fold ( p < 0.05) lower than normal donors, respectively. Intrinsic clearance (CLint) was 2.7- ( p < 0.05) and 4.1 fold ( p < 0.01) lower in donors with NAFL and NASH, respectively. CYP3A4 protein expression was significantly lower in NAFL and NASH donors ( p < 0.05) and accounted for significant midazolam hydroxylation variability in a multiple linear regression analysis (beta = 0.869, r2 = 0.762, P < 0.01). Diabetes was also associated with decreased CYP3A4 activity and protein expression. Both midazolam CLint and CYP3A4 protein abundance decreased significantly with increase in hepatic fat accumulation. Age and gender did not exhibit any significant association with the observed alterations. Predicted midazolam exposure was 1.7- and 2.3-fold higher for NAFL and NASH, respectively, which may result in a longer period of sedation in these disease-states. Data suggests that NAFLD and diabetes are associated with the decreased hepatic CYP3A4 activity. Thus, further evaluation of clinical consequences of these findings on the efficacy and safety of CYP3A4 substrates is warranted. PMID- 29792709 TI - Glycofunctionalization of Poly(lactic- co-glycolic acid) Polymers: Building Blocks for the Generation of Defined Sugar-Coated Nanoparticles. AB - A set of poly(lactic- co-glycolic acid) polymers functionalized with different monosaccharides as well as glycodendrimers and surface-decorated nanoparticles (NPs) were synthesized and characterized. The functionalization of the polymer was carried out through amide bond formation with amino-modified sugar monomers and through a biocompatible chemoselective method exploiting the reducing end of a free sugar. The assemblage of the NPs adopting a nanoprecipitation method was straightforward and allowed the preparation of sugars/sugar dendrimer coated NPs. PMID- 29792710 TI - Measuring the Adhesion Forces for the Multivalent Binding of Vancomycin Conjugated Dendrimer to Bacterial Cell-Wall Peptide. AB - Multivalent ligand-receptor interaction provides the fundamental basis for the hypothetical notion that high binding avidity relates to the strong force of adhesion. Despite its increasing importance in the design of targeted nanoconjugates, an understanding of the physical forces underlying the multivalent interaction remains a subject of urgent investigation. In this study, we designed three vancomycin (Van)-conjugated dendrimers G5(Van) n ( n = mean valency = 0, 1, 4) for bacterial targeting with generation 5 (G5) poly(amidoamine) dendrimer as a multivalent scaffold and evaluated both their binding avidity and physical force of adhesion to a bacterial model surface by employing surface plasmon resonance (SPR) spectroscopy and atomic force microscopy. The SPR experiment for these conjugates was performed in a biosensor chip surface immobilized with a bacterial cell-wall peptide Lys-d-Ala-d-Ala. Of these, G5(Van)4 bound most tightly with a KD of 0.34 nM, which represents an increase in avidity by 2 or 3 orders of magnitude relative to a monovalent conjugate G5(Van)1 or free vancomycin, respectively. By single-molecule force spectroscopy, we measured the adhesion force between G5(Van) n and the same cell wall peptide immobilized on the surface. The distribution of adhesion forces increased in proportion to vancomycin valency with the mean force of 134 pN at n = 4 greater than 96 pN at n = 1 at a loading rate of 5200 pN/s. In summary, our results are strongly supportive of the positive correlation between the avidity and adhesion force in the multivalent interaction of vancomycin nanoconjugates. PMID- 29792711 TI - Interfacial Emulsification: An Emerging Monodisperse Droplet Generation Method for Microreactors and Bioanalysis. AB - The generation of uniform droplets has been extensively investigated owing to its profound potentials both in scientific research and engineering applications. Although various methods have been put forward to expand this area, new innovations are still needed to improve the technical convenience and save instrumental cost. In this feature article, we highlight an interfacial emulsification technique that we developed in the past several years. This technique serves as a platform for preparing uniform droplets that are formed on the air-liquid interface of the continuous phase based on interfacial shearing. Three specific aspects of interfacial emulsification are reviewed, including its basic design and principle, the preparation of droplets with controllable size and adjustable components, and practical applications of the method in bioanalysis, microreactors, and particle synthesis. Compared to other droplet generation methods, several attractive advantages and perspectives for further development have been summarized. PMID- 29792712 TI - Targeted Discovery and Combinatorial Biosynthesis of Polycyclic Tetramate Macrolactam Combamides A-E. AB - Polycyclic tetramate macrolactams (PoTeMs) are a growing class of natural products with distinct structure and diverse biological activities. By promoter engineering and heterologous expression of the cryptic cbm gene cluster, four new PoTeMs, combamides A-E (1-4), were identified. Additionally, two new derivatives, combamides E (5) and F (6), were generated via combinatorial biosynthesis. Together, our findings provide a sound base for expanding the structure diversities of PoTeMs through genome mining and combinatorial biosynthesis. PMID- 29792714 TI - Docking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson's Disease. AB - Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B). Twenty-four compounds that were among the highest ranked for both binding sites were evaluated experimentally, resulting in the discovery of four dual-target ligands. The most potent compound was an A2AAR antagonist with nanomolar affinity ( Ki = 19 nM) and inhibited MAO-B with an IC50 of 100 nM. Optimization guided by the predicted binding modes led to the identification of a second potent dual-target scaffold. The two discovered scaffolds were shown to counteract 6-hydroxydopamine-induced neurotoxicity in dopaminergic neuronal-like SH-SY5Y cells. Structure-based screening can hence be used to identify ligands with specific polypharmacological profiles, providing new avenues for drug development against complex diseases. PMID- 29792713 TI - GaN Nanowire Arrays for Efficient Optical Read-Out and Optoelectronic Control of NV Centers in Diamond. AB - Solid-state quantum emitters embedded in a semiconductor crystal environment are potentially scalable platforms for quantum optical networks operated at room temperature. Prominent representatives are nitrogen-vacancy (NV) centers in diamond showing coherent entanglement and interference with each other. However, these emitters suffer from inefficient optical outcoupling from the diamond and from fluctuations of their charge state. Here, we demonstrate the implementation of regular n-type gallium nitride nanowire arrays on diamond as photonic waveguides to tailor the emission direction of surface-near NV centers and to electrically control their charge state in a p-i-n nanodiode. We show that the electrical excitation of single NV centers in such a diode can efficiently replace optical pumping. By the engineering of the array parameters, we find an optical read-out efficiency enhanced by a factor of 10 and predict a lateral NV NV coupling 3 orders of magnitude stronger through evanescently coupled nanowire antennas compared to planar diamond not covered by nanowires, which opens up new possibilities for large-scale on-chip quantum-computing applications. PMID- 29792715 TI - Quantitative Analysis of Peptide-Matrix Interactions in Lyophilized Solids Using Photolytic Labeling. AB - Peptide-matrix interactions in lyophilized solids were explored using photolytic labeling with reversed phase high performance liquid chromatography (rp-HPLC) and mass spectrometric (MS) analysis. A model peptide (Ac-QELHKLQ-NHCH3) derived from salmon calcitonin was first labeled with a heterobifunctional cross-linker NHS diazirine (succinimidyl 4,4'-azipentanoate; SDA) at Lys5 in solution, with ~100% conversion. The SDA labeled peptide was then formulated with the following excipients at a 1:400 molar ratio and lyophilized: sucrose, trehalose, mannitol, histidine, arginine, urea, and NaCl. The lyophilized samples and corresponding solution controls were exposed to UV at 365 nm to induce photolytic labeling, and the products were identified by MS and quantified with rp-HPLC or MS. Peptide excipient adducts were detected in the lyophilized solids except the NaCl formulation. With the exception of the histidine formulation, peptide-excipient adducts were not detected in solution and the fractional conversion to peptide water adducts in solution was significantly greater than in lyophilized solids, as expected. In lyophilized solids, the fractional conversion to peptide-water adducts was poorly correlated with bulk moisture content, suggesting that the local water content near the labeled lysine residue differs from the measured bulk average. In lyophilized solids, the fractional conversion to peptide excipient adducts was assessed using MS extracted ion chromatograms (EIC); subject to the assumption of equal ionization efficiencies, the fractional conversion to excipient adducts varied with excipient type. The results demonstrate that the local environment near the lysine residue of the peptide in the lyophilized solids can be quantitatively probed with a photolytic labeling method. PMID- 29792716 TI - Options to improve the quality of kidney grafts from expanded criteria donors experimental study. AB - INTRODUCTION: There is a worldwide discrepancy between the number of donors and the number of organs needed for transplantation, leading to certain expansion of criteria, resulting in acceptance of donor organs. This means that organs with worse parenchymal qualities may be harvested for transplantation. One possibility, how to ameliorate the quality of these organs, is to change the concept of their preservation during cold ischemia or even after sudden circulatory arrest, prior to the collection of the organ itself. The goal of our experimental study was to try to improve organ quality from these marginal donors. METHODS: In the first part of our experimental study, we tested retrograde oxygen persufflation (ROP) in preservation of ischemically damaged kidney grafts. In ten animals (domestic pig), we compared standard intra-arterial perfusion of the grafts using cooled perfusion solution (N=5), with a retrograde oxygen persufflation method (N=5). The main criterion for evaluation was the histopathological analysis of renal parenchyma after transplantation of the kidney graft. In the second part of our experimental study, again using an animal model of an ischemic kidney (laboratory rabbit), we compared machine perfusion of the kidney graft with routinely used perfusion by hydrostatic pressure. For evaluation, we added another two criteria - the volume of perfusate that flowed through the graft and the temperature drop during perfusion. RESULTS: In the first part of the study, we proved the ability of ROP to preserve and even ameliorate the quality of ischemically damaged kidney grafts. Results of histopathological analysis of samples taken during ROP were without statistically significant difference in comparison with those taken during standard intra arterial perfusion. In the second part of the study, we observed a significant difference in maximal flow rate measured during perfusion of the kidney grafts, favoring mechanical perfusion over perfusion using hydrostatic pressure (p=0.004). The same situation was seen with the drop of temperature measured in the parenchyma of the grafts (p<0.001). Finally, histopathological evaluation of the renal parenchyma found better washing out of blood particles from the capillaries during mechanical perfusion (p=0.005). CONCLUSION: The presented results of our experimental studies establish that alternative methods of preservation during cold ischemia and before removal of kidney grafts from the donor may be beneficial for its function after transplantation. We believe that these methods may be suitable especially for so-called marginal grafts from extended criteria donors.Key words: transplantation donors after circulatory death controlled organ perfusion in situ perfusion retrograde oxygen persufflation. PMID- 29792717 TI - Postoperative monitoring of colorectal anastomosis - experimental study. AB - INTRODUCTION: Inadequate blood supply is one of the major risk factors for colorectal anastomotic leak. Early postoperative detection of local ischemic changes can predict complicated healing and lead to better outcome. Microdialysis (MD) offers real-time evaluation of adequate bowel perfusion through monitoring of tissue metabolism. The aim of this study was to assess the feasibility of MD for early detection of ischemic changes in colorectal anastomosis. METHOD: Five pigs with end-to-end colorectal anastomosis were included. MD catheter was placed intramurally 5mm from anastomotic edge. Occlusive ischemia was induced after 3 measurements and followed by another 3 hours of monitoring. Tissue levels of different metabolites were measured every 60 minutes before and after ischemia induction. Mann-Whitney test was used to compare pre and post ischemic changes. RESULTS: The monitoring of colorectal anastomosis using MD was technically feasible and associated with no complications. Significant changes caused by local ischemia were observed in decreased levels of glucose or pyruvate and increased levels of lactate and glycerol. All metabolic changes were detectable already in first samples 60 minutes after ischemia induction. CONCLUSION: Postoperative ischemic changes in colorectal anastomosis can be detected by means of microdialysis.Key words: colorectal anastomosis anastomotic leak microdialysis. PMID- 29792718 TI - Fixation of biomaterial to metallic stent and fixation of stents after circular endoscopic dissection in the esophagus on an animal model. AB - INTRODUCTION: Complete circular endoscopic (submucosal) resection (CER) performed using the endoscopic submucosal dissection (ESD) technique is burdened with a high incidence of post-operative strictures in the esophagus. The most effective method of preventing them is not known so far; one of the possible methods is to prevent these strictures directly at the site of their formation by covering the defect with a stent. The aim of the study was to find a way to fix a selected biomaterial to a stent, and subsequently, to fix the stent at the CER site to prevent esophageal strictures in an animal model. METHOD: Miniature piglets from the Czech Academy of Sciences breeding unit in Libechov (N=10) were used. Endoscopy was performed using a single-channel endoscope. First, we made two circular mucosal cuts spaced 5 cm apart in the middle esophagus and we performed the CER between them using the endoscopic submucosal dissection technique. After that, we covered the defect with a stent coated with biomaterial (Xe-Derma(r)) while we tried to prevent stent migration into the stomach. For stent fixation, we tested endo-clips (N=3), the Apollo endoscopic system (N=1) and the suspension technique using two polyamide threads (N=6) anchored in the nasal septum. We performed a control endoscopy, stent removal and subsequent autopsy after 12 weeks. RESULTS: All procedures were completed successfully without serious complications or deaths. Although stents covered with Xe-Derma(r) were applied to the entire resection area, one case of mediastinitis and one paraesophageal abscess were found during autopsy, most likely due to microperforations caused during the procedure. Histological analysis showed that after contact with the biomaterial, re-epithelisation took place within one week of application to the resection area. Stent migration occurred in each case when the stent was attached to the esophageal wall by endo-clips or with the endoscopic suture system (Apollo). There was no stent dislocation in the cases where the stent was suspended by two polyamide threads. CONCLUSION: We developed a technique of fixing biomaterial to the surface of metallic stents which we used to prevent the formation of esophageal strictures after CER. Distal suspension fixation of the stent with a polyamide thread proved to be the most effective, while fixations by endo-clips or with the endoscopic suture system were ineffective.Key words: benign esophageal strictures circular endoscopic resection endoscopic submucosal dissection complication prevention. PMID- 29792719 TI - [Sinusoidal obstruction syndrome induced by monocrotaline in a large animal experiment - a pilot study]. AB - INTRODUCTION: Sinusoidal obstruction syndrome (SOS) is a disease which is caused by toxic injury to hepatic sinusoids. This syndrome is most frequently caused by myeloablative radiochemotherapy in patients before hematopoietic stem cells transplantation and also by oxaliplatin mainly in patients with colorectal liver metastases. The aim of this study was to establish a large animal model of SOS, which would enable further study of this disease and facilitate translation of experimental outcomes into human medicine. METHODS: A total of 27 domestic pigs (Prestice Black-Pied pig) were involved in this study (12 females). A group with a higher dose of monocrotaline (180 mg/kg) included 5 animals, and the remaining 22 pigs formed another group with a lower dose (36 mg/kg). Monocrotaline was administered via the portal vein and one week after the administration, partial hepatectomy of the left lateral liver lobe was performed. The animals were followed up for 3 weeks after monocrotaline administration. Regular ultrasound examinations were performed as well as examination of biochemical markers of liver and kidney functions and histological examination of liver parenchyma samples. RESULTS: The features of toxic liver injury which we observed in case of all animals were comparable with macroscopic and microscopic appearance of SOS. We recorded AST, ALT, bilirubin and ammonia elevation after monocrotaline administration. Echogenicity on ultrasound images of injured liver parenchyma was higher compared to echogenicity of healthy parenchyma. All the five animals from the first group with a higher monocrotaline dose had died before partial hepatectomy (1st-3rd day after monocrotaline administration). Death before partial hepatectomy occurred in 3 cases (6th and 7th day after monocrotaline administration) in the second group of 22 animals with a lower dose of monocrotaline. Death after partial hepatectomy occurred in 8 cases (7th-17th day after moncrotaline administration) in the same group. 11 animals survived the entire experimental period. The cause of death (in both groups) was metabolic failure in 10 animals and exsanguination in 4 animals, both due to severe hepatopathy. Death of 2 animals was not associated with monocrotaline intoxication (strangulation of small intestine, gastrectasis). CONCLUSIONS: We established a large animal model of SOS induced by monocrotaline administration (36 mg/kg via portal vein). This model can contribute to research of therapeutic modalities for this disease or to evaluation of surgical treatment of patients with SOS.Key words: sinusoidal obstruction syndrome monocrotaline oxaliplatin hepatotoxicity experimental model. PMID- 29792720 TI - [Experimental processing of corrosion casts of large animal organs]. AB - INTRODUCTION: Corrosion casts (CCs) are used for the visualization and assessment of hollow structures. CCs with filled capillaries enable (with the help of imaging methods) to obtain data for mathematical organ perfusion modelling. As the processing is more difficult in case of organs with greater volume of the vasculature, mainly organs from small animals have been cast up to now. The aim of this study was to optimize the protocol of corrosion casting of different organs of pig. Porcine organs are relatively easily accessible and frequently used in experimental medicine. METHOD: Organs from 10 healthy Prestice Black-Pied pigs (6 females, body weight 35-45 kg), were used in this study (liver, spleen, kidneys and small intestine). The organs were dissected, heparin was administered into the systemic circulation and then the vascular bed of the organs was flushed with heparinized saline either in situ (liver) or after their removal (spleen, kidney, small intestine). All handling was done under the water surface to prevent air embolization. The next step was an intraarterial (in case of the liver also intraportal) administration of Biodur E20(r) (Heidelberg, Germany) resin. After hardening of the resin the organ tissue was dissolved by 15% KOH and the specimen was rinsed with tap water. Voluminous casts were stored in 70% denatured alcohol, the smaller ones were lyophilized. The casts were assessed with a stereomicroscope, computed and microcomputed tomography (CT and microCT), a scanning electron microscope (SEM) and high-resolution digital microscope (HRDM). RESULTS: High-quality CCs of the porcine liver, kidneys, spleen and small intestine were created owing to the sophisticated organ harvesting, the suitable resin and casting procedure. Macroscopic clarity was improved thanks to the possibility of resin dying. Scanning by CT was performed and showed to be a suitable method for the liver cast examination. MicroCT, SEM and HRDM produced images of the most detailed structures of vascular bed. Despite the fact that SEM seems to be an irreplaceable method for CCs quality control, it seems that this modality could be partly replaced by HRDM. MicroCT enabled to obtain data about three-dimensional layout of the vascular bed and data for mathematical modelling of organ perfusion. With regard to the quality of the CCs, they could also be used to teach human anatomy. CONCLUSIONS: The protocol of the corrosion casting of the porcine liver, kidneys, spleen and small intestine CCs was optimized. Thanks to different imaging methods, the CCs can be used as a source of data on three-dimensional architecture of the vascular bed. These data can be used for mathematical modeling of organ perfusion which can be helpful for example for optimization of organ resections.Key words: corrosion casts microvasculature Biodur E20(r) domestic pig animal model. PMID- 29792721 TI - [Use of viscoelastic methods in surgery]. AB - INTRODUCTION: Major liver resections are associated with high morbidity and mortality. The main causes of this fact include a significant blood loss which may be associated with this surgical procedure. Hemocoagulation disorder, diagnosed by standard laboratory tests, is very frequent in the postoperative period and often requires the administration of blood derivatives. Several recent studies, however, have questioned the presence of such coagulopathy when viscoelastic methods are used to assess the coagulation process. The studies have concluded that that the coagulation disorder only exists at a laboratory level, the coagulation process itself being unaffected, and no therapeutic intervention is therefore needed. The use of viscoelastic methods may play a crucial role in deciding whether or not to correct the assumed coagulation disorder. METHOD: Our study was designed as a prospective observational study. Data were collected in the Surgical Intensive Care Unit during one year (1 January - 31 December 2016). The study included 18 patients who underwent major liver resection. When coagulation disorder was diagnosed using standard coagulation tests in the postoperative period, we performed a ROTEM examination. The results of the standard and ROTEM examination were then compared. RESULTS: Out of the total of 18 patients enrolled in the study, a coagulopathy was diagnosed in 15 cases (83%) using standard coagulation tests. In these patients, we performed rotational tromboelastometry (ROTEM) which did not show any coagulation disorder. CONCLUSION: Our study has demonstrated that when viscoelastic methods are used to evaluate the function of blood clotting in patients after major hepatic surgery, no coagulopathy has been found as opposed to the evaluation with standard blood clotting tests. Unnecessary transfusions of blood derivatives can be avoided as well as all risks linked to their administration. Viscoelastic methods of coagulation assessment (ROTEM, TEG) help provide a detailed insight into the coagulation process and our observations have shown that they should play a significant role in the postoperative assessment of patients following major hepatic resections.Key words: ROTEM - viscoelastic methods - coagulopathy. PMID- 29792722 TI - [Laparoscopic versus open left pancreatectomy: surgical stress response comparison in the porcine model]. AB - INTRODUCTION: Although several techniques of laparoscopic left pancreatectomy have already been developed through experiments on animals and human patients, there is still insufficient information about their pathophysiological mechanisms, especially the impact on surgical stress. METHOD: In a group of 10 pigs, open left pancreatectomy was performed, and the other group of 10 pigs underwent laparoscopic left pancreatectomy. Postoperative stress was compared by determining serum levels of leukocytes, interleukin 1, 6 and CRP from peripheral venous blood collection. The blood was collected prior to incision, 1 and 2 hours after incision, 24 hours after the beginning of the procedure, and on the 7th postoperative day. RESULTS: No statistically significant difference was found between open and laparoscopic left pancreatectomy in the measured values of leukocytes, IL-1 and 6 and CRP.Key words: laparoscopy - left pancreatectomy surgical stress response interleukin 1 interleukin 6. PMID- 29792723 TI - [Experimental promotion of liver regeneration after portal vein branch ligation]. AB - INTRODUCTION: Portal vein embolization or ligation (PVE/PVL) is part of most multi-stage liver procedures in the case of low future liver remnant volume (FLRV). PVE initiates compensatory hypertrophy of non-occluded liver parenchyma. This hypertrophy is stimulated by an increased volume of portal blood in the non occluded veins. PVE results in adequate FLRV growth necessary for resection only in 63-96% patients. The aim of this publication is to summarize the possibilities of influencing liver regeneration after PVE/PVL in an experiment using cytokines (TNF-alpha, IL-6), a monoclonal antibody against TGF-beta1 (MAB TGF-beta1) and mesenchymal stem cells (MSC). METHODS: The experimental model of PVE/PVL was chosen as best compatible for potential use in human medicine. 9 (control group), 9 (TNF-alpha group), 8 (IL-6 group), 6 (MSC group) and 7 piglets (MAB TGF-beta1 group) were enrolled in individual studies. We performed laparotomy with PVL of the right-sided liver lobes under general anaesthesia. The following amounts of substances were applied in the non-occluded portal vein branches immediately after PVL: physiological solution (control group), recombinant porcine TNF-alpha (5 MUg/kg), recombinant porcine IL-6 (0.5 MUg/kg) and MSC (8.75, 14.0, 17.0, 17.5, 43.0 and 61.0 x 106 MSC). MAB TGF-beta1 was applied 24 hours after PVL (40 MUg/kg). Biochemical parameters were analysed repeatedly and FLRV ultrasound assessments were performed in the postoperative period. The experiments were ended on postoperative day 14 by sacryfiing the animals under general anaesthesia. Liver samples of hypertrophic and atrophic liver parenchyma were analysed. RESULTS: Repeated ultrasound assessments of the effects of MSC, TNF alpha, IL-6 and MAB TGF-beta1 compared with the physiological solution in the control group demonstrated statistically significant acceleration of FLRV growth in the experimental groups. For MSC, maximum growth was observed between postoperative days 3 and 7, on day 7 for TNF-alpha, between days 3 and 7 for MAB TGF-beta1 and on day 7 for IL-6. Serum levels of AST and ALT increased after PVL and MSC whereas other biochemical parameters showed no statistically significant differences. We identified individual MSC using immunohistochemistry in the hypertrophic tissue of the MSC group. A statistically significant difference was observed in the number of binucleated hepatocytes, with their increased concentration in the IL-6 group. CONCLUSION: Application of IL-6, TNF-alpha, MAB TGF-beta1 and MSC seems to provide suitable stimulation for achieving faster FLRV growth. Nevertheless, many controversial questions still remain to be answered with respect to the mechanism of their respective effects.Key words: liver regeneration portal vein embolization large animal experiment mesenchymal stem cells cytokines. PMID- 29792724 TI - A systematic understanding of signaling by ErbB2 in cancer using phosphoproteomics. AB - ErbB2 is an important receptor tyrosine kinase and a member of the ErbB family. Although it does not have a specific ligand, it transmits signals downstream by heterodimerization with other receptors in the family. It plays a major role in a variety of cellular responses like proliferation, differentiation, and adhesion. ErbB2 is amplified at the DNA level in breast cancer (20%-30%) and gastric cancer (10%-20%), and trastuzumab is effective as a therapeutic antibody. This review is a critical analysis of the currently published data on the signaling pathways of ErbB2 and the interacting proteins. It also focuses on the techniques that are currently available to evaluate the entire phosphoproteome following activation of ErbB2. Identification of new and relevant phosphoproteins can not only serve as new therapeutic targets but also as a surrogate marker in patients to assess the activity of compounds that inhibit ErbB2. Overall, such analysis will improve understanding of signaling by ErbB2. PMID- 29792725 TI - Novel Breast Imaging and Machine Learning: Predicting Breast Lesion Malignancy at Cone-Beam CT Using Machine Learning Techniques. AB - OBJECTIVE: The purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers. SUBJECTS AND METHODS: Five machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity. RESULTS: The clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p < 0.001). CONCLUSION: Machine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity. PMID- 29792727 TI - Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI. AB - OBJECTIVE: FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. MATERIALS AND METHODS: We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. RESULTS: Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. CONCLUSION: Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients. PMID- 29792726 TI - I Like Them...Will They Like Me? Evidence for the Role of the Ventrolateral Prefrontal Cortex During Mismatched Social Appraisals in Anxious Youth. AB - OBJECTIVE: Socially anxious adolescents report distress during social decision making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as "mismatch bias." The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. METHOD: The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI. Participants completed a novel task where they viewed silent videos of unknown peers. After viewing each video, participants appraised the social desirability of the peer ("How much do you think you would like them [if you met them]") or predicted how socially desirable the peer would find them ("How much do you think they would like you [if you met them]"). Each participant's mismatch bias was calculated as the difference between their appraisal of peers and their prediction of peers' appraisal of them. RESULTS: We found that anxious youth exhibited mismatch bias: they rated unknown peers as more desirable than they predicted peers would rate them. This effect was not present in the healthy group. Mismatch biases were associated with increased engagement of the ventrolateral prefrontal cortex (vlPFC), a region broadly involved in flexible cognitions and behavioral selection. In addition, greater mismatch biases and vlPFC activation during mismatch biases were associated with more severe anxiety symptoms. CONCLUSIONS: The findings highlight the importance of understanding mismatch biases to inform treatments that target distress elicited by discrepant social appraisals in anxious youth. PMID- 29792728 TI - Single-Acquisition Triple-Bolus Dual-Energy CT Protocol for Comprehensive Evaluation of Renal Masses: A Single-Center Randomized Noninferiority Trial. AB - OBJECTIVE: The primary objective of this study was to compare triple-bolus dual energy CT (DECT) against standard triple-phase MDCT in terms of appropriateness of patient treatment. SUBJECTS AND METHODS: One hundred twenty-four patients with suspected renal masses seen at ultrasound were randomized into triple-bolus DECT and triple-phase MDCT groups. Patients in the triple-bolus DECT group underwent synchronous corticomedullary nephrographic delayed-phase triple-bolus DECT. In the triple-phase MDCT group, single-energy triple-phase scans were acquired after an unenhanced scan. The primary outcome was appropriateness of treatment received at 1 year. The predefined noninferiority limit was 10%. Histopathologic analysis or follow-up confirmed the benign or malignant nature of the masses. Diagnostic accuracy to differentiate benign from malignant masses was calculated. Size specific dose estimates were compared. RESULTS: After excluding six patients, 118 patients were analyzed (62 triple-bolus DECT; 56 triple-phase MDCT). Treatment appropriateness was not significantly different (p = 0.9397) between the two groups (61/62 [98.39%; 95% CI, 95.26-101.52%] for triple-bolus DECT vs 55/56 [98.21%; 95% CI, 94.74-101.68%] for triple-phase MDCT). The absolute difference was 0.18% (95% CI, -4.48% to 4.84%). Both techniques had similar diagnostic accuracy (sensitivity, 98.25% vs 96.67%; specificity, 98.17% vs 97.97%). The mean (+/- SD) size-specific dose estimate was significantly lower for triple-bolus DECT than for triple-phase MDCT (19.02 +/- 4.07 vs 57.04 +/- 15.17 mGy; p < 0.0001). CONCLUSION: Single-acquisition triple-bolus DECT is noninferior to triple-phase MDCT, with similar diagnostic accuracy but delivering significantly less radiation. PMID- 29792730 TI - Nivolumab for the treatment of colorectal cancer. AB - INTRODUCTION: Despite a variety of therapies for advanced metastatic colorectal cancer being available, the outcomes in this malignancy remain suboptimal. Immunotherapy has been slow to impact the management of this patient group. Checkpoint inhibitors, such as nivolumab, have had disappointing results when used broadly. However, for the subset of patients with microsatellite unstable colorectal cancer, the use of checkpoint inhibitors such as nivolumab appears to be transformative, and will provide a new therapeutic option for patient with advanced disease. Areas covered: Nivolumab gained regulatory approval for the treatment of dMMR/MSI-H metastatic colorectal cancer in mid 2017. The current review will summarize the clinical evidence of checkpoint inhibitors in metastatic colorectal cancer, with a focus on nivolumab. Expert commentary: For patients with dMMR/MSI-H mCRC, the use of nivolumab has now been shown to have objective and sustained clinical responses in a pivotal phase II trial. While additional data are limited, the therapeutic role for augmenting an immune response in metastatic colorectal cancer is likely to continue to expand. Further combination trials of nivolumab with immunologic and non-immunologic agents are ongoing. PMID- 29792732 TI - Phosphatidylinositol 3-kinase beta and delta isoforms play key roles in metastasis of prostate cancer DU145 cells. AB - Metastasis is the main cause of the lethality of prostate cancer. Class I phosphatidylinositol 3-kinases (PI3Ks), which contain 4 isoforms, alpha, beta, delta, and gamma, are known to play important roles in cell growth, migration, invasion, and so on. However, the respective role of each PI3K isoform in cancer cell migration and invasion remains unknown. In a study that aimed to elucidate the respective role of the 4 PI3K isoforms, we investigated the change in migratory and invasive ability of DU145 cells after treatment with each PI3K isoform-specific inhibitor. Both migration and invasion of DU145 cells were potently blocked by each of the PI3Kbeta inhibitors (GSK2636771 and TGX221) and PI3Kdelta inhibitors (CAL101 and IC87114) while not obviously affected by PI3Kalpha inhibitor BYL719 or PI3Kgamma inhibitor AS252424. Furthermore, knocking down PI3Kbeta or PI3Kdelta isoform led to a significant decrease in migration of DU145. The results suggest that PI3Kbeta and PI3Kdelta play key roles in prostate cancer cell migration, while PI3Kalpha and PI3Kgamma might be redundant. Oral administration of GSK2636771 (100 mg/kg) and CAL101 (30 mg/kg) inhibited tumor growth in bone, an experimental model by intratibia injection of DU145 cells, with improved bone structure and bone mineral density analyzed by micro-computed tomography. Tissue staining indicated reduction of metastatic DU145 cells and osteoclasts in the bones of GSK2636771- and CAL101-treated mice compared to the untreated group. In summary, our results indicated the distinct roles of 4 PI3K isoforms in the migration of prostate cancer DU145 cells, and they demonstrated the in vitro and in vivo antimetastatic effect of PI3K-isoform specific inhibitors, most of which are in clinical trials.-Zhang, Z., Liu, J., Wang, Y., Tan, X., Zhao, W., Xing, X., Qiu, Y., Wang, R., Jin, M., Fan, G., Zhang, P., Zhong, Y, Kong, D. Phosphatidylinositol 3-kinase beta and delta isoforms play key roles in metastasis of prostate cancer DU145 cells. PMID- 29792731 TI - APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells. AB - Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis related protein 3 (APR3) was recently discovered after treatment with all- trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity. Overexpression of APR3 revealed its mitochondrial localization and induced a robust production of reactive oxygen species that was accompanied by impaired mitochondrial oxygen consumption, complex activity, and lower ATP content, resulting in significant changes in mitochondrial structure, which may contribute to cell apoptosis. High doses of all- trans retinoic acid treatment were found to significantly induce APR3 expression, increase reactive oxygen species levels, and decrease ATP content, which were abolished by knockdown of APR3. These results indicate that APR3 plays a vital role in regulating redox status and mitochondrial activity and thus suggest APR3 might be a potential novel target for study of treatment of age-related macular degeneration.-Li, Y., Zou, X., Gao, J., Cao, K., Feng, Z., Liu, J. APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells. PMID- 29792729 TI - 90-kVp low-tube-voltage CT pulmonary angiography in combination with advanced modeled iterative reconstruction algorithm: effects on radiation dose, image quality and diagnostic accuracy for the detection of pulmonary embolism. AB - OBJECTIVE: To evaluate low-tube-voltage 90-kVp CT pulmonary angiography (CTPA) with advanced modeled iterative reconstruction algorithm (Admire) compared to 120 kVp equivalent dual-energy (DE) acquisition with regards to radiation exposure, image quality and diagnostic accuracy for pulmonary embolism (PE) assessment. METHODS: CTPA studies of 40 patients with suspected PE (56.7 +/- 16.3 years) performed on a third-generation 192-slice dual-source CT scanner were retrospectively included. 120-kVp equivalent linearly-blended (60% 90-kVp, 40% 150-kVp) and 90-kVp images were reconstructed. Attenuation and noise of the pulmonary trunk were measured to calculate contrast-to-noise ratios (CNR). Three radiologists assessed the presence of central and segmental PE and diagnostic confidence. Interobserver agreement was calculated using intraclass correlation coefficient (ICC). Radiation exposure was assessed as effective dose (ED). RESULTS: Pulmonary trunk CNR values were significantly increased in 90-kVp compared to linearly-blended series (15.4 +/- 6.3 vs 11.3 +/- 4.6, p < 0.001). Diagnostic accuracy for PE assessment was similar in both series with excellent interobserver agreement (p = 0.48; ICC, 0.83; p = 0.48). Overall confidence for PE assessment was rated excellent for both series with a significant advantage for linearly-blended series (p < 0.001; 4.1 vs 3.8). ED was reduced by 37.2% with 90-kVp compared to 120-kVp equivalent image series (1.1 +/- 0.6 vs 1.7 +/- 0.7 mSv, p < 0.001). CONCLUSION: 90-kVp CTPA with Admire provided increased quantitative image quality with similar diagnostic accuracy and confidence for PE assessment compared to 120-kVp equivalent acquisition, while radiation dose was reduced by 37.2%. Advances in knowledge: 90-kVp CTPA with an advanced iterative reconstruction algorithm results in excellent image quality and reduction of radiation exposure without limiting diagnostic performance. PMID- 29792733 TI - Feasibility and Acceptability of Nurse-Led Primary Palliative Care for Older Adults with Chronic Conditions: A Pilot Study. AB - BACKGROUND: Many older adults live with serious illness for years before their death. Nurse-led primary palliative care could improve their quality of life and ability to stay in their community. OBJECTIVES: To assess feasibility and acceptability of a nurse-led Transitional Palliative Care (TPC) program for older adults with serious illness. METHODS: The study was a pilot trial of the TPC program in which registered nurses assisted patients with symptom management, communication with care providers, and advance care planning. Forty-one older adults with chronic conditions were enrolled in TPC or standard care groups. Feasibility was assessed through enrollment and attrition rates and degree of intervention execution. Acceptability was assessed through surveys and exit interviews with participants and intervention nurses. RESULTS: Enrollment rate for those approached was 68%, and completion rate for those enrolled was 71%. The TPC group found the intervention acceptable and helpful and was more satisfied with care received than the control group. However, one-third of participants perceived that TPC was more than they needed, despite the number of symptoms they experienced and the burdensomeness of their symptoms. More than half of the participants had little to no difficulty participating in daily activities. CONCLUSION: This study demonstrated that the nurse-led TPC program is feasible, acceptable, and perceived as helpful. However, further refinement is needed in selection criteria to identify the population who would most benefit from primary palliative care before future test of the efficacy of this intervention. PMID- 29792734 TI - Clinical updates on perianal fistulas in Crohn's disease. AB - INTRODUCTION: Perianal fistulizing disease is an aggressive and debilitating phenotype of Crohn's disease (CD), representing a significant therapeutic challenge. New work has led to advancement in epidemiology and long-term outcomes of perianal disease. The range of therapeutic options continues to expand, including new biologic agents, biosimilars, and stem cell therapy. Areas covered: We discuss updates to all aspects of management of perianal disease, with a focus on the last 3 years of published data. Areas considered include new data on epidemiology and prognostication, medical and surgical therapy, and stem cell therapy. Expert commentary: The presence of perianal disease at CD diagnosis portends a significantly worse disease course. Patients with perianal disease require close monitoring to identify those who are at risk for worsening disease, suboptimal biologic drug levels, and signs of developing neoplasm. With the impending availability of local mesenchymal stem cell therapy, this becomes increasingly important as this therapy, although extremely promising, is thus far only effective in patients without proctitis. PMID- 29792736 TI - Overutilization of Health Care Resources for Breast Pain. AB - OBJECTIVE: The objective of this study is to analyze the incidence of women with breast pain who present to an imaging center and assess the imaging findings, outcomes, and workup costs at breast imaging centers affiliated with one institution. MATERIALS AND METHODS: Demographic characteristics of and imaging findings for female patients presenting with breast pain at three community breast imaging centers between January 1, 2014, and December 31, 2014, were reviewed. Patients who were pregnant, were lactating, had a history of breast cancer, or presented with palpable nipple or skin findings were excluded. RESULTS: A total of 799 patients met the study criteria. Pain was diffuse in 30%, was focal in 30%, and was not localized in 40%. Of the 799 patients with breast pain, 790 (99%) presented for a diagnostic evaluation; 759 (95%) of these evaluated patients had negative findings. A benign sonographic correlate was detected in the area of pain in 5% of patients (39/799). One patient had a single cancer detected in the contralateral asymptomatic breast. When correlations between breast pain and the presence of cancer in the study patients were compared with the concurrent cancer detection rate in the screening population (5.5 cases per 1000 examinations performed), breast pain was not found to be a sign of breast cancer (p = 0.027). Patients younger than 40 years (316/799) underwent a total of 454 workup studies for breast pain; all findings were benign, and the cost of these studies was $87,322. Patients 40 years or older (483/799) underwent 745 workup studies, for a cost of $152,732. CONCLUSION: Breast pain represents an area of overutilization of health care resources. For female patients who present with pure breast pain, breast imaging centers should consider the following imaging protocols and education for referring physicians: an annual screening mammogram should be recommended for women 40 years or older, and reassurance without imaging should be offered to patients younger than 40 years. PMID- 29792735 TI - Hip Fracture in the Setting of Limited Life Expectancy: The Importance of Considering Goals of Care and Prognosis. AB - IMPORTANCE: Many older patients with a limited life expectancy experience fragility fracture of the hip, and this event is associated with increased risk of premature mortality, functional decline, and institutionalization. The treating team, in collaboration with patients and their families, must determine whether a surgical or conservative approach is in the patient's best interest when a patient has limited life expectancy. OBSERVATION: Goals of care discussions appear to be rare in the setting of fragility fracture. The urgent nature of the problem makes such discussions challenging. We believe that many physicians have not considered goals of care discussions to be a standard component of fragility fracture management. CONCLUSIONS: We propose that physicians caring for patients with limited life expectancy and fragility fracture of the hip should initiate a goals of care discussion to help determine whether operative repair will be the most patient-centered approach. Training on conducting goals of care discussions should be a standard part of surgical training programs. Goals of care discussions should include prognosis, patient values and preferences, pain, likelihood for functional recovery, and burdens and benefits of surgical versus nonsurgical management. Multidisciplinary input is required, and many patients will benefit from geriatric and/or palliative care team involvement. PMID- 29792737 TI - Assessing the Recall Rate for Screening Mammography: Comparing the Medicare Hospital Compare Dataset With the National Mammography Database. AB - OBJECTIVE: High-quality screening mammography has been shown to substantially reduce mortality from breast cancer. Recall rate is a principal performance metric for screening mammography because it directly relates to the rate of false positive examinations. This study aims to compare the recall rate derived using two sources-the claims-based Hospital Compare (HC) dataset from the Centers for Medicare & Medicaid Services versus the National Mammography Database (NMD) from the American College of Radiology-to understand the implications in pay-for performance and quality improvement activities. MATERIALS AND METHODS: This study retrospectively compared the recall rate reported by NMD facilities with that reported in the HC dataset. Site matching was performed by facility name and zip code, followed by manual verification. Scatterplots, correlations, a paired t test, and Bland-Altman analysis were performed to assess association between the two measures. RESULTS: During the period from October 1 to December 1, 2016, 92 facilities were unambiguously matched using 2014-2015 records in both datasets. The recall rates were positively correlated (r = 0.428, p < 0.001), but the mean HC recall rate (8.5% +/- 2.86% [SD]) was significantly (p < 0.001) lower than the mean NMD recall rate (10.6% +/- 3.90%). CONCLUSION: The NMD and HC are two commonly used datasets for measuring screening mammography recall rate. Although recall rates are correlated at the individual facility level, there are important differences that have implications for quality improvement and pay-for performance. PMID- 29792738 TI - Integrated Interventional Radiology Residency Program Websites: A Development in Progress. AB - OBJECTIVE: The purpose of this study is to evaluate the comprehensiveness of interventional radiology (IR) residency program websites. MATERIALS AND METHODS: We determined whether all integrated IR residency programs approved in 2016 by the Society for Interventional Radiology had a dedicated residency program website. On each website, we searched for 38 elements identified as important considerations for medical students applying to diagnostic radiology residency and IR fellowship programs. With the use of t tests and ANOVA, both the prevalence of criteria between regions and program sizes were compared. RESULTS: Of 61 IR residency programs that were identified, 44 (72%) had dedicated websites. On average, the websites included 38% of the 38 elements evaluated. Only two residency program websites (5%) included more than 50% of the criteria assessed. The information most commonly found was a contact e-mail (95% of websites), a mailing address (91%), and a comprehensive listing of faculty (75%). The information that was least commonly included was clinical responsibility progression (7%), a description of didactics (5%), and simulation experience (5%). No significant difference in website comprehensiveness was noted between regions (p = 0.590) or between different quartiles of ranking of IR fellowship on an online social networking service for U.S. clinicians (p = 0.198). CONCLUSION: Nearly one-third of integrated IR residency programs do not have a dedicated website. Those that do exist are inadequately comprehensive, with less than 40% of assessed criteria present. Contact information and information about life outside of work were the most commonly included elements, with a description of clinical training opportunities less frequently included. Addressing these gaps in website content will help IR residency programs better inform prospective students and may increase the number of applicants. PMID- 29792739 TI - X-Ray Phase-Contrast Technology in Breast Imaging: Principles, Options, and Clinical Application. AB - OBJECTIVE: The purpose of this article is to review different x-ray phase contrast breast imaging techniques and their potential application in clinical settings. CONCLUSION: Phase-contrast imaging depicts not only the absorption contrast but also the refraction contrast of the transmitted x-ray beam. Early data suggest that this new modality may overcome some of the diagnostic limitations associated with current clinically available mammography systems and that it has potential for improving breast cancer detection. PMID- 29792740 TI - Colloid Adenocarcinoma of the Lung: CT and PET/CT Findings in Seven Patients. AB - OBJECTIVE: We aimed to assess CT and 18F-FDG PET/CT findings of colloid adenocarcinoma of the lung in seven patients. MATERIALS AND METHODS: From 2010 to 2017, seven patients with surgically proven colloid adenocarcinoma of the lung were identified. CT (both enhanced and unenhanced) and PET/CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed. RESULTS: In all cases except one, tumors showed low attenuation on unenhanced CT scans, ranging in attenuation from -16.5 to 20.7 HU (median, 9.2 HU). After contrast medium injection, enhancement was scant, so net enhancement ranged from 0.4 to 29.0 HU (median, 4.1 HU). All tumors had a lobulated contour. Stippled calcifications within the tumor were seen in one patient. The maximum standardized uptake value of tumors on PET/CT ranged from 1.5 to 4.5 (median, 3.5). In six of seven patients, FDG accumulation was seen in the tumor walls (n = 3, curvilinear uptake) or in both the tumor walls and tumor septa (n = 3, crisscross uptake). Six patients were alive without recurrence after a median follow-up period of 2.3 years (range, 2 months to 5 years). In one patient, who was alive at follow-up 4 years after imaging and had received adjuvant concurrent chemoradiation therapy after lobectomy, recurrent disease was detected 6 months after completion of the therapy. CONCLUSION: On CT, pulmonary colloid adenocarcinomas present as lobulated homogeneously low-attenuation tumors. At PET, curvilinear or crisscross FDG uptake is seen within the tumor where tumor cells are lining the walls or septal structures. PMID- 29792741 TI - Mesenchymal Lesions of the Breast: What Radiologists Need to Know. AB - OBJECTIVE: Mesenchymal breast tumors originate from the various components of mammary stroma. The aim of this review is to discuss the clinical presentation, imaging appearance, and management of mesenchymal breast lesions. CONCLUSION: Although many mesenchymal tumors exhibit characteristic findings on imaging, others show nonspecific characteristics and require tissue biopsy for diagnosis. An awareness of the clinical and imaging presentation is essential in guiding the differential diagnosis and patient management. PMID- 29792742 TI - Screening Mammography Findings From One Standard Projection Only in the Era of Full-Field Digital Mammography and Digital Breast Tomosynthesis. AB - OBJECTIVE: The purpose of this article is to compare outcomes of findings seen on one view only from screening full-field digital mammography (FFDM) and FFDM plus digital breast tomosynthesis (DBT). MATERIALS AND METHODS: A retrospective review was performed of 103,070 consecutive screening mammograms obtained from February 2011 through June 2014 at two community-based breast centers. Recalled findings prospectively seen on one view only were analyzed. Pearson chi-square test and Fisher exact test were performed, and 95% CIs were determined. RESULTS: Mammograms were acquired using FFDM (n = 71,656) and FFDM-DBT (n = 31,414) during the study period, and 2213 FFDM (3.1%) and 433 FFDM-DBT (1.4%) mammograms were recalled for one-view-only findings (p < 0.0001). The final study population (1592 FFDM and 354 FFDM-DBT) was defined after 689 of these recalled FFDM and 92 of these recalled FFDM-DBT examinations were excluded for insufficient mammographic follow-up (< 24 months). Summation artifacts accounted for more one view-only findings from FFDM (1067/1592; 67.0%) than FFDM-DBT (190/354; 53.7%) (p < 0.0001). In the FFDM cohort, 28 one-view-only findings proved malignant (24 invasive ductal carcinoma [IDC], one invasive lobular carcinoma [ILC], and three ductal carcinoma in situ [DCIS]). In the FFDM-DBT cohort, 14 one-view-only findings proved malignant (11 IDC, one ILC, and two DCIS). The positive predictive value (PPV) of a one-view-only finding was significantly lower for FFDM (1.8%) than for FFDM-DBT (4.0%) (p = 0.010). CONCLUSION: One-view-only findings occur with both FFDM and FFDM-DBT and remain an important but uncommon sign of malignancy. They are more frequent, are more likely to represent summation artifacts, and have a lower PPV with FFDM than with FFDM-DBT. PMID- 29792743 TI - Lesions of Ligamentum Teres: Diagnostic Performance of MRI and MR Arthrography-A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The purpose of this study is to determine the diagnostic performance of MRI and MR arthrography for depicting ligamentum teres lesions. MATERIALS AND METHODS: A literature search was performed. Original studies reporting the diagnostic accuracy of MRI examinations for the depiction of ligamentum teres lesions were included. RESULTS: Eight studies entailing 1456 MRI examinations were included (frequency of median ligamentum teres injury, 25.9%; interquartile range, 14.1-45.3%). Two studies reported the results of unenhanced MRI examinations, and their diagnostic performance could not be estimated. Sensitivity, specificity, and diagnostic odds ratio (DOR) of all MRI examinations were 64.7%, 86.9%, and 12.2, respectively, whereas the sensitivity, specificity, and DOR of MR arthrography examinations were 82.2%, 88.6%, and 35.9, respectively. The heterogeneity (I2) for all MRI and MR arthrography examinations was 92.3% and 88.2%, respectively. Five blinded MR arthrography studies with 643 MR arthrography examinations found an appropriate threshold effect for summary ROC construction (AUC, 0.95). The summary estimate of these studies yielded a sensitivity of 87.8%, a specificity of 91%, and DOR of 73.1. The heterogeneity (I2) for this group was 64.3%. In patients with low pretest probability (25%), MR arthrography enabled the exclusion of ligamentum teres lesion (postprobability for a negative result, 4%; negative likelihood ratio, 0.13). CONCLUSION: MR arthrography can depict ligamentum teres lesions with high accuracy. However, its diagnostic performance for differentiating various types of ligamentum teres lesions (partial, complete ligamentum teres tears, and hypertrophic ligamentum teres), as well as the diagnostic performance of unenhanced MRI for the depiction of ligamentum teres lesions, is yet to be determined because of the paucity of reported data in the literature. PMID- 29792744 TI - JOURNAL CLUB: Extracolonic Findings at CT Colonography: Systematic Review and Meta-Analysis. AB - OBJECTIVE: The purpose of this study was to perform a systematic review and meta analysis of published studies on CT colonography (CTC) in which extracolonic findings were assessed. MATERIALS AND METHODS: A systematic review of studies of screening CTC and of CTC to evaluate symptoms (1994-June 2017) was conducted to estimate the rate of extra-colonic findings and associated additional workup recommendations. The primary outcome was potentially important extracolonic findings, defined as CT Colonography Imaging Reporting and Data System (C-RADS) category E4 or as having high clinical importance (if C-RADS was not used). Secondary outcomes included likely unimportant extracolonic findings (i.e., C RADS category E3 or similar). Random-effects and meta-regression analyses were used to generate pooled estimates and to explore risk factors for extracolonic findings related to various cohort characteristics. RESULTS: Primary data were acquired from 44 studies (49,676 patients). The pooled rate of potentially important extracolonic findings was 4.9% (95% CI, 3.7-6.4%) with a high degree of heterogeneity (I2 = 95%). This estimate progressively declined over time (9% per year since 2006) and was significantly related to the reporting system (lower for C-RADS than for low, moderate, high clinical significance reporting). C-RADS specific meta-analysis (32,746 patients) showed rates of potentially significant extracolonic findings in 2.8% (95% CI, 1.9-3.5%) of the cohort without symptoms and 5.2% (95% CI, 3.5-7.6%) of the cohort with symptoms and in 5.7% (95% CI, 3.3 9.8%) of seniors (>= 65 years) versus 2.3% (95% CI, 1.2-4.5%) of those younger than 65 years. The overall pooled rates of recommended workup were 8.2% (95% CI, 6.6-10.1%) for all extracolonic findings and 4.0% (95% CI, 2.7-5.9%) for potentially important extracolonic findings. CONCLUSION: With use of the more robust C-RADS classification, potentially important extracolonic findings at CTC occur in less than 3% of cohorts without symptoms. For all extracolonic findings, the rate of suggested or recommended additional workup is approximately 8% but decreases to 4% for potentially important extracolonic findings. PMID- 29792745 TI - Postoperative MRI of Massive Rotator Cuff Tears. AB - OBJECTIVE: The aim of this article is to review the postoperative MRI appearances of irreparable massive rotator cuff tears (RCTs) after surgery was performed using newer techniques, including patch repair, muscle tendon transfer, superior capsular reconstruction, and subacromial balloon implantation. CONCLUSION: Newer surgical techniques are emerging for the management of massive RCTs. As radiologists become increasingly likely to encounter postoperative imaging studies of RCTs repaired using these techniques, familiarity with the normal postoperative appearances and complications associated with these techniques becomes important. PMID- 29792746 TI - High-Resolution CT Findings of Obstructive and Restrictive Phenotypes of Chronic Lung Allograft Dysfunction: More Than Just Bronchiolitis Obliterans Syndrome. AB - OBJECTIVE: The purpose of this article is to review the high-resolution CT characteristics of individual obstructive and restrictive chronic lung allograft dysfunction (CLAD) phenotypes to aid in making accurate diagnoses and guiding treatment. CONCLUSION: Long-term survival and function after lung transplant are considerably worse compared with after other organ transplants. CLAD is implicated as a major limiting factor for long-term graft viability. Historically thought to be a single entity, bronchiolitis obliterans syndrome, CLAD is actually a heterogeneous group of disorders with distinct subtypes. PMID- 29792747 TI - Interpretation Time Using a Concurrent-Read Computer-Aided Detection System for Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense Breast Tissue. AB - OBJECTIVE: The purpose of this study was to compare diagnostic accuracy and interpretation time of screening automated breast ultrasound (ABUS) for women with dense breast tissue without and with use of a recently U.S. Food and Drug Administration-approved computer-aided detection (CAD) system for concurrent read. MATERIALS AND METHODS: In a retrospective observer performance study, 18 radiologists interpreted a cancer-enriched set (i.e., cancer prevalence higher than in the original screening cohort) of 185 screening ABUS studies (52 with and 133 without breast cancer). These studies were from a large cohort of ABUS screened patients interpreted as BI-RADS density C or D. Each reader interpreted each case twice in a counterbalanced study, once without the CAD system and once with it, separated by 4 weeks. For each case, each reader identified abnormal findings and reported BI-RADS assessment category and level of suspicion for breast cancer. Interpretation time was recorded. Level of suspicion data were compared to evaluate diagnostic accuracy by means of the Dorfman-Berbaum-Metz method of jackknife with ANOVA ROC analysis. Interpretation times were compared by ANOVA. RESULTS: The ROC AUC was 0.848 with the CAD system, compared with 0.828 without it, for a difference of 0.020 (95% CI, -0.011 to 0.051) and was statistically noninferior to the AUC without the CAD system with respect to a margin of -0.05 (p = 0.000086). The mean interpretation time was 3 minutes 33 seconds per case without the CAD system and 2 minutes 24 seconds with it, for a difference of 1 minute 9 seconds saved (95% CI, 44-93 seconds; p = 0.000014), or a reduction in interpretation time to 67% of the time without the CAD system. CONCLUSION: Use of the concurrent-read CAD system for interpretation of screening ABUS studies of women with dense breast tissue who do not have symptoms is expected to make interpretation significantly faster and produce noninferior diagnostic accuracy compared with interpretation without the CAD system. PMID- 29792748 TI - Portal Vein Thrombosis: Imaging the Spectrum of Disease With an Emphasis on MRI Features. AB - OBJECTIVE: The purpose of this article is to review the classic and uncommon imaging findings of portal vein thrombosis (PVT) (acute, chronic, congenital, and septic thrombus) as visualized on multiple modalities, with an emphasis on MRI findings. Additional aims are to understand the imaging of obliterative portal venopathy and its clinical significance, appreciate morphologic changes of the biliary system that may accompany PVT, and recognize changes in liver enhancement patterns seen with PVT related to the hepatic arterial buffer response. The review also addresses morphologic changes of the liver that may occur after PVT, including nodular regenerative hyperplasia, central hepatic hypertrophy, and peripheral fibrosis that may stimulate cirrhosis, as well as the importance of portal vein mapping and the diagnostic findings and clinical significance of tumor within the portal vein in the liver transplant population. CONCLUSION: PVT may be a complication of liver cirrhosis, but it may also occur as a primary vascular disorder without liver disease. PVT can result in portal hypertension and may present with variceal bleeding or hypersplenism. Radiologists should be familiar with the imaging of PVT in patients of various ages and in different clinical scenarios. PVT can influence hepatic perfusion, the shape of the bile ducts, and liver architecture. Bland PVT and tumor-related PVT have major implications for hepatic transplant. PMID- 29792749 TI - Engagement with a Text-Messaging Intervention Improves Adherence in Adolescents with Type 1 Diabetes: Brief Report. AB - Adherence to diabetes management is a challenge for adolescents with type 1 diabetes (T1D). Positive psychology interventions have improved adherence to treatment recommendations in adults with chronic health conditions but have not been widely tested in pediatric populations. We hypothesized that higher engagement with a text-messaging intervention to promote positive affect would increase the effects on diabetes management among adolescents with T1D. Adolescents with T1D (n = 48) and their caregivers were randomized to either an attention control condition or a novel positive psychology intervention delivered through personalized automated text messaging. We examined rates of engagement (percent response to text messages) in relation to demographic factors, and we explored the effect of engagement in relation to adherence and glycemic control. Adolescent engagement was good (mean response rate of 76%) over the 8-week intervention. Engagement was related to adolescents' gender, race, baseline glycemic control, and blood glucose monitoring, but not to treatment type (pump vs. injection), diabetes duration, age, or household income. There was a significant effect of level of engagement on better caregiver-reported adherence, but adolescents' engagement was not related to self-reported adherence or glycemic control. These results indicate feasibility and initial efficacy of using automated text-messaging to deliver an intervention aimed at promoting adherence in adolescents with T1D. PMID- 29792750 TI - Metrics to Evaluate Quality of Glycemic Control: Comparison of Time in Target, Hypoglycemic, and Hyperglycemic Ranges with "Risk Indices". AB - OBJECTIVE: We sought to cross validate several metrics for quality of glycemic control, hypoglycemia, and hyperglycemia. RESEARCH DESIGN AND METHODS: We analyzed the mathematical properties of several metrics for overall glycemic control, and for hypo- and hyperglycemia, to evaluate their similarities, differences, and interrelationships. We used linear regression to describe interrelationships and examined correlations between metrics within three conceptual groups. RESULTS: There were consistently high correlations between %Time in range (%TIR) and previously described risk indices (M100, Blood Glucose Risk Index [BGRI], Glycemic Risk Assessment Diabetes Equation [GRADE], Index of Glycemic Control [IGC]), and with J-Index (J). There were also high correlations among %Hypoglycemia, Low Blood Glucose Index (LBGI), percentage of GRADE attributable to hypoglycemia (GRADE%Hypoglycemia), and Hypoglycemia Index, but negligible correlation with J. There were high correlations of percentage of time in hyperglycemic range (%Hyperglycemia) with High Blood Glucose Index (HBGI), percentage of GRADE attributable to hyperglycemia (GRADE%Hyperglycemia), Hyperglycemia Index, and J. %TIR is highly negatively correlated with %Hyperglycemia but very weakly correlated with %Hypoglycemia. By adjusting the parameters used in IGC, Hypoglycemia Index, Hyperglycemia Index, or in MR, one can more closely approximate the properties of BGRI, LBGI, or HBGI, and of GRADE, GRADE%Hypoglycemia, or GRADE%Hyperglycemia. CONCLUSIONS: Simple readily understandable criteria such as %TIR, %Hypoglycemia, and %Hyperglycemia are highly correlated with and appear to be as informative as "risk indices." The J Index is sensitive to hyperglycemia but insensitive to hypoglycemia. PMID- 29792752 TI - Expanding the Reach of Early Psychosis Intervention. PMID- 29792751 TI - Glucose Sensing in the Subcutaneous Tissue: Attempting to Correlate the Immune Response with Continuous Glucose Monitoring Accuracy. PMID- 29792755 TI - Dalangtan Saline Playa in a Hyperarid Region on Tibet Plateau: I. Evolution and Environments. AB - Since 2008, we have been studying a saline lake, Dalangtan (DLT) Playa, and its surroundings in a hyperarid region of the Qaidam Basin on the Tibetan Plateau as a potential Mars analog site. We describe the evolution of saline deposits in the Qaidam Basin (including DLT), based on investigative findings accumulated over the course of 60 years of geological surveys. In addition, we report regional meteorological patterns recorded for the past 32 years along with meteorological station recorded data at DLT since 2012. Overall, the DLT area on the Tibetan Plateau has low atmospheric pressure, high ultraviolet radiation, low annual mean temperatures (T) but large seasonal and diurnal T cycles, and extremely low relative humidity, all of which bear some similarities with the equatorial region on Mars. In addition, salt types similar to those found on Mars, such as magnesium-sulfates, chlorides, and perchlorates, are found at the surface and subsurface in the DLT area (and the other two playas in the Qaidam Basin), thus supporting DLT as a Mars analog in terms of mineralogy and geochemistry. PMID- 29792754 TI - Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab. AB - Purpose Patients with metastatic colorectal cancer (mCRC) have limited benefit from the addition of bevacizumab to standard chemotherapy. However, a subset probably benefits substantially, highlighting an unmet clinical need for a biomarker of response to bevacizumab. Previously, we demonstrated that losses of chromosomes 5q34, 17q12, and 18q11.2-q12.1 had a significant correlation with progression-free survival (PFS) in patients with mCRC treated with bevacizumab in the CAIRO2 clinical trial but not in patients who did not receive bevacizumab in the CAIRO trial. This study was designed to validate these findings. Materials and Methods Primary mCRC samples were analyzed from two cohorts of patients who received bevacizumab as first-line treatment; 96 samples from the European multicenter study Angiopredict (APD) and 81 samples from the Italian multicenter study, MOMA. A third cohort of 90 samples from patients with mCRC who did not receive bevacizumab was analyzed. Copy number aberrations of tumor biopsy specimens were measured by shallow whole-genome sequencing and were correlated with PFS, overall survival (OS), and response. Results Loss of chromosome 18q11.2 q12.1 was associated with prolonged PFS most significantly in both the cohorts that received bevacizumab (APD: hazard ratio, 0.54; P = .01; PFS difference, 65 days; MOMA: hazard ratio, 0.55; P = .019; PFS difference, 49 days). A similar association was found for OS and overall response rate in these two cohorts, which became significant when combined with the CAIRO2 cohort. Median PFS in the cohort of patients with mCRC who did not receive bevacizumab and in the CAIRO cohort was similar to that of the APD, MOMA, and CAIRO2 patients without an 18q11.2-q12.1 loss. Conclusion We conclude that the loss of chromosome 18q11.2 q12.1 is consistently predictive for prolonged PFS in patients receiving bevacizumab. The predictive value of this loss is substantiated by a significant gain in OS and overall response rate. PMID- 29792756 TI - Uterine or paracervical lidocaine application for pain control during intrauterine contraceptive device insertion: a meta-analysis of randomised controlled trials. AB - OBJECTIVE: Systematic review and meta-analysis to assess the effects of uterine or paracervical lidocaine application on pain control during IUD insertion. METHODS: PubMed and five other electronic research databases were searched through 15 November 2017 for RCTs comparing lidocaine treatment vs. a control (placebo or no-intervention) to prevent pain during IUD insertion. Searched terms included 'IUD insertion', 'lidocaine' and 'randomised controlled trial'. RCTs evaluating lidocaine treatment before IUD insertion without restriction of language, age and IUD type. Pain measured by visual pain scales at tenaculum placement, IUD insertion and immediate post-IUD insertion. Results of random effects meta-analyses were reported as mean differences (MDs) of visual pain scale (VPS) scores and their 95% confidence intervals (CIs). RESULTS: Eleven RCTs (n = 1458 women) reporting paracervical lidocaine block or uterine mucosa lidocaine application before IUD insertion. Lidocaine produced lower VPS scores during tenaculum placement (MD -0.99, 95% CI: -1.73 to -0.26), IUD insertion (MD 1.26, 95% CI: -2.23 to -0.29) and immediate post-IUD insertion period (MD -1.25, 95% CI: -2.17 to -0.33). CONCLUSION: Lidocaine treatment was associated with modest reduction of pain during tenaculum placement and after IUD insertion. PMID- 29792757 TI - FIELD TRIALS OF ONTARIO RABIES VACCINE BAIT IN THE NORTHEASTERN USA, 2012-14. AB - In the US, rabies virus (RV) has been enzootic in raccoons ( Procyon lotor) since the late 1940s. Oral rabies vaccination (ORV) was implemented in the 1990s to halt the spread of raccoon RV and continues to be used as a wildlife management tool. Our objective was to evaluate a recombinant human adenovirus-rabies virus glycoprotein vaccine in northern New York, Vermont, and New Hampshire over a 3-yr period, using changes in RV neutralizing antibody (RVNA) seroprevalence in raccoon populations as an immunologic index of ORV impact. Vaccine baits were distributed at 75 baits/km2 and 750-m flight-line spacing in the study area. Animal sampling occurred during 10-d intervals pre- and post-ORV during 2012-14 within eight study cells: four northern cells had a history of ORV with a different vaccine for 3 or more years prior and four southern cells were ORV naive. Baseline raccoon RVNA seroprevalence was 27.3% ( n=1,079, 95% confidence interval [CI]: 24.8-30.1) before ORV in 2012. Raccoon RVNA seroprevalence averaged 68.5% ( n=1,551, 95% CI: 66.2-70.8) post-ORV during the 3-yr study. The RVNA seroprevalence levels in this study were considered to be adequate for stopping raccoon RV transmission and supported and expanded the results from a West Virginia field trial, as well as earlier evaluations along the Canada-US border. PMID- 29792758 TI - Investigation of a Large-Scale Gopher Tortoise ( Gopherus polyphemus) Mortality Event on a Public Conservation Land in Florida, USA. AB - In August 2015, a gopher tortoise ( Gopherus polyphemus) mortality event was documented on a 40-ha area of Lake Louisa State Park, Lake County, Florida, US. To quantify the extent of the die-off and the seroprevalence of Mycoplasma agassizii and Mycoplasma testudineum, two causative agents of mycoplasmal upper respiratory tract disease (URTD), we conducted a tortoise shell survey on 25 and 26 August 2015 and collected blood samples from live tortoises on 2-4 September 2015 and 1-13 August 2016 within the area of documented mortality. We discovered 94 shells and measured the degree of disarticulation to estimate time since mortality. Results indicated that most mortalities likely occurred more than 3 yr before discovery. Of the 42 blood samples collected in 2016, 31% ( n=13) tested positive, 17% ( n=7) were suspect, and 52% ( n=22) were negative for M. agassizii antibodies; all blood samples were negative for M. testudineum. Sixty-nine percent (9/13) of seropositive tortoises exhibited clinical signs of URTD, and seropositive individuals were more likely to express clinical signs than seronegative tortoises. However, 32% (7/22) of seronegative individuals also exhibited some clinical signs, including naris and eye abnormalities. We suggest additional research to determine causality of this mortality event, as well as examine risks associated with its spread. PMID- 29792759 TI - Hematologic Parameters and Viral Status for Zika, Chikungunya, Bluetongue, and Epizootic Hemorrhagic Disease in White-tailed Deer ( Odocoileus virginianus) on St. John, US Virgin Islands. AB - A population of white-tailed deer ( Odocoileus virginianus) resides throughout the island of St. John, US Virgin Islands, predominately in the Virgin Islands National Park. Adult deer ( n=23), ranging from 1 yr to 8 yr old, were assessed to characterize body condition and health. Serologic samples were screened for important viral pathogens in the area, including Zika, chikungunya, bluetongue, and epizootic hemorrhagic disease viruses. Samples were collected in July 2016; males were in velvet and all females were in diestrus. Deer had recovered from a severe drought the previous year but were generally healthy, with a low-level but high incidence of tick parasitism. Marked statistically significant changes in hematocrit and hemoglobin levels were associated with the effects of the anesthetic mixture used for capture. No other statistically significant differences were observed. Serum from four deer induced reduction in Zika virus plaques, suggesting possible exposure. No serum was reactive for chikungunya virus. Bluetongue and epizootic hemorrhagic disease antibodies were present in 50% of the sampled deer, but no clinical signs associated with disease were observed during the study period. These data will be valuable for future dynamic health assessment and may help assess changes to the population, such as those induced by climate change, infectious disease, or other demographic events. PMID- 29792760 TI - Seroprevalence of Equine Herpesviruses 1 and 9 (EHV-1 and EHV-9) in Wild Grevy's Zebra ( Equus grevyi) in Kenya. AB - Equid herpesviruses types 1 (EHV-1) and 9 (EHV-9) are unusual among herpesviruses in that they lack strong host specificity, and the full extent of their host range remains unclear. The virus establishes latency for long periods and can be reactivated and shed, resulting in clinical disease in susceptible species. A sensitive and specific peptide-based enzyme-linked immunosorbent assay was developed to study the seroprevalence of both viruses in a broad range of species among both wild and captive populations. We used this assay to study the seroprevalences of EHV-1 and EHV-9 in a natural population of the highly endangered Grevy's zebra ( Equus grevyi) in Kenya, sampled during a 4-yr period (2012-15). The results were compared with those obtained from captive Grevy's zebras from a previous study. The wild population had a significantly higher seroprevalence of EHV-9 compared with the captive population, suggesting that captivity might reduce exposure to this serotype. In contrast, the seroprevalences of EHV-1 between captive and wild groups was not significantly different. The seroprevalence of EHV-9 was not significantly higher than EHV-1 in zebras within the wild Kenyan population. PMID- 29792761 TI - Theileriosis in Multiple Neonatal White-tailed Deer ( Odocoileus virginianus) in Delaware, USA. AB - Postmortem examination of 21 neonatal white-tailed deer ( Odocoileus virginianus) from Delaware, US identified six fawns with Theileria spp. organisms or suspected infection. PMID- 29792762 TI - Genetic profiling in acute myeloid leukemia: a path to predicting treatment outcome. AB - INTRODUCTION: Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool. The role of next generation sequencing, run on qPCR/digital PCR platforms or polyvalent ones such as the Nanostring NCounterTM and RNA-sequencing techniques in the near future will also be briefly discussed. Expert commentary: The authors believe that a combination of genetic (including both germline and somatic data), epigenetic and transcriptional data will represent, in the future, the molecular basis for treatment decision with the highest predictive potential. PMID- 29792763 TI - Overlapping molecular signaling of IRX-2 and Ta1 resulting in synergistic biological activity. PMID- 29792766 TI - Research roundup. AB - Synopses of a selection of recently published research articles of relevance to palliative care. PMID- 29792764 TI - Use of a depression and sleep impairment treatment guideline to improve quality of life for patients with sickle cell disease. AB - BACKGROUND: Pain in sickle cell disease (SCD) is often joined by other affective disorders such as depression and/or sleep impairment that can impact pain levels and quality of life (QoL). AIM: To develop a guideline to improve the process of assessment and treatment of depression and sleep impairment in patients admitted with SCD. METHOD: An interdisciplinary team used the Stetler model to create the Guideline for the Evaluation and Treatment of Depression and Sleep Impairment in Sickle Cell Disease. Patients were assessed, offered treatments and reassessed during the project period. RESULTS: Both depression and QoL scores showed significant improvement by the end of the project. Significant correlations were found between pain, depression and sleep; depression, pain, sleep and QoL; sleep, pain and depression; and QoL and depression. CONCLUSIONS: Interdisciplinary teams are effective in creating a guideline to assess and treat depression and sleep impairment and their effects on pain and QoL in patients with SCD. PMID- 29792765 TI - Exploring the relationship between volunteering and hospice sustainability in the UK: a theoretical model. AB - AIM: To explore the relationship between volunteering and the sustainability of UK voluntary hospices. METHODS: A narrative literature review was conducted to inform the development of a theoretical model. Eight databases were searched: CINAHL (EBSCO), British Nursing Index, Intute: Health and Life Sciences, ERIC, SCOPUS, ASSIA (CSA), Cochrane Library and Google Scholar. RESULTS: A total of 90 documents were analysed. Emerging themes included the importance of volunteering to the hospice economy and workforce, the quality of services, and public and community support. Findings suggest that hospice sustainability is dependent on volunteers; however, the supply and retention of volunteers is affected by internal and external factors. CONCLUSIONS: A theoretical model was developed to illustrate the relationship between volunteering and hospice sustainability. It demonstrates the factors necessary for hospice sustainability and the reciprocal impact that these factors and volunteering have on each other. The model has a practical application as an assessment framework and strategic planning tool. PMID- 29792767 TI - Politics and palliative care: Zambia. AB - Dion Smyth's review of palliative nursing on the internet. PMID- 29792768 TI - Thai nursing students' experiences of caring for patients at the end of life: a phenomenological study. AB - AIM: To describe Thai nursing students' experiences of providing end-of-life care (EoLC). METHODS: Data were collected via in-depth interviews with 21 nursing students and were analysed using Van Manen's method. FINDINGS: Eight themes emerged based on Van Manen's four lived worlds: feeling excited and worried when receiving an assigned case; feeling disappointed with the health-care team's provision of psychosocial support for patients at the end-of-life and their families; being in a time of uncertainty; recognising that EoLC is a time for gaining merit; knowing that a peaceful place and privacy are needed for promoting a peaceful death; knowing that the real-life classroom is around the patient's bedside; feeling lonely and needing help and support; and creating relationships with patients and families as a nurse. CONCLUSIONS: To promote nursing students' positive clinical experiences in providing EoLC, enhancing staff's competency and closing the theory-practice gap regarding palliative care are necessary objectives. PMID- 29792769 TI - The evidence of early specialist palliative care on patient and caregiver outcomes. AB - Although there are many differences regarding what palliative care is and to whom it should be delivered, its delivery and integration earlier in the disease trajectory have been advocated since 1990. More recently, there has been a heightened interest in early access to specialist palliative care through its provision earlier in the disease trajectory to improve patient and caregiver outcomes. This article explores the challenges in understanding and defining 'early' specialist palliative care. It also examines the available evidence on early specialist palliative care interventions and their association with patient and caregiver outcomes. Finally, recommendations for future direction of research and practice are discussed. PMID- 29792771 TI - Is blogging a new form of communication in palliative health care? A qualitative research study. AB - AIM: To illuminate experiences of living with life-threatening diseases as described in blogs and the experience of blogging about these matters. METHODS: A secondary analysis of 21 blogs was performed. RESULTS: It was difficult for bloggers to accept what they perceived to be the unacceptable aspects of having an life-threatening disease. They searched for hope and acceptance, and tried to manage their life. They felt strengthened by supportive encounters with health professionals, relatives, friends, and from their blogging. However, they also felt that they were set aside in relation to both health professionals and relatives. CONCLUSION: These patients appreciated being able to express their feelings and received support from their readers. Even if patient blogs can be used in health care, research and education, there is a lack of research studies that have examined the benefits of using blogging for any of these purposes. PMID- 29792772 TI - Genome Sequence Resources for the Wheat Stripe Rust Pathogen (Puccinia striiformis f. sp. tritici) and the Barley Stripe Rust Pathogen (Puccinia striiformis f. sp. hordei). AB - Puccinia striiformis f. sp. tritici causes devastating stripe (yellow) rust on wheat and P. striiformis f. sp. hordei causes stripe rust on barley. Several P. striiformis f. sp. tritici genomes are available, but no P. striiformis f. sp. hordei genome is available. More genomes of P. striiformis f. sp. tritici and P. striiformis f. sp. hordei are needed to understand the genome evolution and molecular mechanisms of their pathogenicity. We sequenced P. striiformis f. sp. tritici isolate 93-210 and P. striiformis f. sp. hordei isolate 93TX-2, using PacBio and Illumina technologies and RNA sequencing. Their genomic sequences were assembled to contigs with high continuity and showed significant structural differences. The circular mitochondria genomes of both were complete. These genomes provide high-quality resources for deciphering the genomic basis of rapid evolution and host adaptation, identifying genes for avirulence and other important traits, and studying host-pathogen interactions. PMID- 29792773 TI - Experiential or Material Purchases? Social Class Determines Purchase Happiness. AB - Which should people buy to make themselves happy: experiences or material goods? The answer depends in part on the level of resources already available in their lives. Across multiple studies using a range of methodologies, we found that individuals of higher social class, whose abundant resources make it possible to focus on self-development and self-expression, were made happier by experiential over material purchases. No such experiential advantage emerged for individuals of lower social class, whose lesser resources engender concern with resource management and wise use of limited finances. Instead, lower-class individuals were made happier from material purchases or were equally happy from experiential and material purchases. PMID- 29792774 TI - When the Good Looks Bad: An Experimental Exploration of the Repulsion Effect. AB - When people are choosing among different options, context seems to play a vital role. For instance, adding a third option can increase the probability of choosing a similar dominating option. This attraction effect is one of the most widely studied phenomena in decision-making research. Its prevalence, however, has been challenged recently by the tainting hypothesis, according to which the inferior option contaminates the attribute space in which it is located, leading to a repulsion effect. In an attempt to test the tainting hypothesis and explore the conditions under which dominated options make dominating options look bad, we conducted four preregistered perceptual decision-making studies with a total of 301 participants. We identified two factors influencing individuals' behavior: stimulus display and stimulus design. Our results contribute to a growing body of literature showing how presentation format influences behavior in preferential and perceptual decision-making tasks. PMID- 29792775 TI - A narrative review of the technical standards for extracorporeal life support devices (pumps and oxygenators) in Europe. AB - This review summarizes the European rules to control the market when introducing new products. In particular, it shows all the steps to achieve the European Conformity (CE Mark), a certification that all new medical products must achieve before being used in Europe. Extracorporeal membrane oxygenation (ECMO) devices are exposed to the same procedures. Hereby, we present some regulatory issues regarding pumps and oxygenators, providing technical details as released by the manufacturers on their websites and information charts. PMID- 29792777 TI - Dismantling a complex of anther smuts (Microbotryum) on carnivorous plants in the genus Pinguicula. AB - The anther smuts of the genus Microbotryum are known from host plant species belonging to the Caryophyllaceae, Dipsacaceae, Lamiaceae, Lentibulariaceae, Montiaceae, and Primulaceae. Of these, the anther smuts on Caryophyllaceae, in particular on Silene spp., are best known because they include model organisms studied in many disciplines of fungal biology. For Microbotryum species parasitic on Caryophyllaceae, a high degree of host specificity was revealed and several cryptic species were described. In contrast, the host specificity within Microbotryum pinguiculae occurring in anthers of different Pinguicula species (Lentibulariaceae) has not been investigated in detail until now. The anther smuts on Pinguicula alpina, P. villosa, and P. vulgaris, on which M. pinguiculae was described, were analyzed using nuc rDNA ITS1-5.8S-ITS2 and nuc rDNA 28S D1-D2 sequences and morphology to determine if they belong to one polyphagous species or rather represent three host-specific species. The results of the morphological investigations revealed no decisive differences between the anther smuts on different Pinguicula species. However, genetic divergence and molecular phylogenetic analyses, which split the specimens according to host plant species, supported host specificity of the anther smuts on different Pinguicula species. Accordingly, in addition to Microbotryum pinguiculae s. str. on Pinguicula vulgaris, M. alpinum sp. nov. on P. alpina from Europe and M. liroi sp. nov. on P. villosa from Asia are described and illustrated. PMID- 29792776 TI - Prevalence of Inadequate Immunity to Measles, Mumps, Rubella, and Varicella in MLB and NBA Athletes. AB - BACKGROUND: Multiple outbreaks of vaccine-preventable viral diseases have occurred in professional sports in recent years. Currently, there is no established protocol for vaccination or immunity screening for professional athletes. HYPOTHESIS: There are significant differences in the prevalence of inadequate immunity dependent on age, sport, country of birth, and participation in collegiate sports. STUDY DESIGN: Cross-sectional cohort study. LEVEL OF EVIDENCE: Level 4. METHODS: A sample of Major League Baseball (MLB) and National Basketball Association (NBA) players were screened for serologic evidence of immunity to measles, mumps, rubella, and varicella prior to the 2015 and 2016 seasons. The results were designated as adequate (immune) or inadequate (equivocal or nonimmune) based on laboratory criteria. Comparison with an age matched control group was performed using data from the National Health and Nutrition Examination Survey (NHANES). RESULTS: A total of 98 athletes (62 MLB, 36 NBA) were screened. The prevalence of inadequate immunity for any virus was 35.5% in MLB players and 33.3% in NBA players. There was a significantly greater risk of inadequate immunity to rubella (risk ratio, 6.38; P < 0.01) and varicella (risk ratio, 4.21; P < 0.01) in athletes compared with the age-matched NHANES population. Our analysis did not reveal differences in rates of immunity based on sport, country of birth (US born vs international), or participation in college athletics. There was a lower rate of inadequate immunity to varicella with increasing age (odds ratio, 0.72; P = 0.05). CONCLUSION: One-third of athletes studied had inadequate immunity to 1 of the 4 viruses tested. Younger players had a significantly greater risk of inadequate immunity to varicella. Birth outside the US and lack of participation in college athletics were not found to influence immunity rates. CLINICAL RELEVANCE: These results can inform the development of future screening programs to prevent outbreaks of viral infections in professional athletes. PMID- 29792779 TI - Association of Colistin-Resistant KPC Clonal Strains with Subsequent Infections and Colonization and Biofilm Production. AB - Carbapenemase-producing organisms are pandemic and a significant threat to public health. We investigated the clonal relatedness of colistin-resistant Klebsiella pneumoniae strains producing KPC-type carbapenemase (KPC-KP) causing subsequent infections or colonization. Moreover, we aimed to gain insight into the ability of biofilm production in K. pneumoniae strains producing carbapenemase. Twenty two consecutive KPC-KP and one KPC-negative strain was identified from an adult intensive care unit in Brazil. Seventy-five percent of isolates that harbored the blaKPC gene exhibited genetic relatedness by pulsed-field gel electrophoresis, and none presented the plasmid-mediated mcr-1 and blaNDM genes. This study showed that the majority of repeated KPC infections in adults were caused by a clone that caused the previous infections/colonizations even after a long period of time and illustrates the capacity of multiple clones producing biofilms to coexist in the same patient at the same time, becoming a reservoir of KPC-KP in the hospital environment. PMID- 29792778 TI - Does Iron Supplementation Improve Performance in Iron-Deficient Nonanemic Athletes? AB - CONTEXT: Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports. OBJECTIVES: To investigate the benefits of iron on performance, identify a ferritin level cutoff in IDNA athletes, and determine which iron supplementation regimens are most effective. DATA SOURCES: A search of the PubMed, CINAHL, Embase, ERIC, and Cochrane databases was performed in 2014 including all articles. Citations of pertinent review articles were also searched. In 2017, the search was repeated. STUDY SELECTION: Inclusion criteria comprised studies of level 1 to 3 evidence, written in the English language, that researched iron supplementation in nonanemic athletes and reported performance outcomes. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: The search terms used included athletic performance, resistance training, athletes, physical endurance, iron, iron deficiency, supplement, non-anemic, low ferritin, ferritin, ferritin blood level, athletes, and sports. RESULTS: A total of 1884 studies were identified through the initial database search, and 13 were identified through searching references of relevant review articles. A subsequent database search identified 46 studies. Following exclusions, 12 studies with a total of 283 participants were included. Supplementing IDNA athletes with iron improved performance in 6 studies (146 participants) and did not improve performance in the other 6 studies (137 participants). In the 6 studies that showed improved performance with iron supplementation, all used a ferritin level cutoff of <=20 MUg/L for treatment. Additionally, all studies that showed improved performance used oral iron as a supplement. CONCLUSION: The evidence is equivocal as to whether iron supplementation in IDNA athletes improves athletic performance. Supplementing athletes with ferritin levels <20 MUg/L may be more beneficial than supplementing athletes with higher baseline ferritin levels. PMID- 29792781 TI - Is blaCTX-M-1 Riding the Same Plasmid Among Horses in Sweden and France? AB - A predominance of the blaCTX-M-1/IncHI1 plasmid combination in horses has been reported in Czech-Republic, Denmark, and The Netherlands. To clarify a possible specific plasmid epidemiology of blaCTX-M-1 in horses in a European perspective, a collection of 74 extended-spectrum beta-lactamase-producing Escherichia coli recovered from diseased horses in France and Sweden during the period 2009-2014 was investigated in respect of their genetic relatedness, plasmid content, and molecular features. Overall, 80% of E. coli isolates from diseased horses harbored blaCTX-M-1 on large IncHI1 plasmids with plasmid sequence type (pST) 2 and pST9 more prevalent in Sweden and France, respectively. In French isolates, IncI1/pST3 plasmids were also identified. The CTX-M-1-producing E. coli belonged principally to the clonal complex 10. ST641, together with its single locus variant, and ST1730 constituted two other major groups. The rep-PCR clustering highlighted a clonal dissemination of E. coli CTX-M-1 producers in different regions of the same country and during several years. The STs found in our isolates were also reported in The Netherlands, suggesting a common source of contamination in Europe, although only further cooperative investigation will clarify this issue. On the other hand, the spread of IncI1/pST3 plasmids among horses constitutes another worrisome issue considering their successful spread in other animal hosts such as chicken or bovines. Monitoring evolution and propagation of antimicrobial resistance in equine environment is a priority to avoid further propagation of antimicrobial resistance mechanisms threatening human and animal health. PMID- 29792782 TI - 25-Hydroxyvitamin D3 and 1,25 Dihydroxyvitamin D3 as an Antiviral and Immunomodulator Against Herpes Simplex Virus-1 Infection in HeLa Cells. AB - The antiviral and immunomodulatory role of vitamin D has been shown in various viral infections. However, there is scanty literature available about the effect of vitamin D supplementation in herpes simplex virus-1 (HSV-1) infection. Therefore, the present study aimed to evaluate the role of two different forms of vitamin D: 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3) against HSV-1 in HeLa cells. The HeLa cells were supplemented with either 25D3 or 1,25D3 before HSV-1 infection and were studied after 6, 12, and 24 h postinfection (p.i.). The mRNA levels of toll-like receptors (TLRs), (2, 3, 4, 7, and 9), vitamin D signaling genes, and HSV-1 were studied using real-time PCR. The HSV-1 DNA load was estimated in culture supernatant. The supplementation of 25D3 and 1,25D3 significantly downregulated the mRNA levels of TLR2 (p < 0.0001) at 12 h p.i. The mRNA levels of TLR9 were found to be significantly downregulated in 1,25D3-supplemented cells at 12 h p.i. Furthermore, the significant downregulation was observed in HSV-1 titer in both 25D3- and 1,25D3-supplemented cells at 24 h p.i.(p < 0.0001). However, the effect of 25D3 supplementation persisted till 24 h p.i. with significant downregulation of TLR2 (p < 0.05) mRNA levels. The supplementation of both 25D3 and 1,25D3 before HSV-1 infection was found to downregulate the viral titer and TLR2 mRNA during the intial phase of infection. However, the effect of 25D3 supplementation was found to last for a longer duration compared with 1,25D3. PMID- 29792780 TI - Cardiovascular Screening Practices and Attitudes From the NCAA Autonomous "Power" 5 Conferences. AB - BACKGROUND:: The development of athlete-specific electrocardiogram (ECG) interpretation standards, along with recent rates of sudden cardiac death (SCD) in athletes being higher than previously estimated, has heightened the debate in the sports medicine community regarding cardiovascular screening of the college athlete, including whether certain high-risk subsets, such as male basketball athletes, should undergo more intensive screening. HYPOTHESIS:: ECG and/or echocardiography screening in National Collegiate Athletic Association Autonomous 5 Division I (A5DI) schools will be more common than previous reports, and there will be more frequent use of noninvasive cardiac screening for men's basketball players than the general athlete population. STUDY DESIGN:: Cross-sectional, quantitative study. LEVEL OF EVIDENCE:: Level 4. METHODS:: The head team physician for each of the 65 schools in the A5DI conferences was contacted to complete an anonymous survey regarding cardiovascular screening practices at their institution. The survey inquired about current screening protocols, whether SCD epidemiology (SCD-E) was considered in establishing those practices, and whether awareness of present epidemiology altered physician attitudes toward screening. RESULTS:: A total of 45 of the 65 team physicians (69%) responded. All schools reported performing history and a physical evaluation. While 17 (38%) perform only history and physical, 26 (58%) also include an ECG, and 12 (27%) include echocardiography for all student-athletes. Specifically for male basketball athletes, 10 (22%) schools perform only history and physical, 32 (71%) include ECG, and 20 (45%) include echocardiography. Additionally, 64% reported using SCD-E in developing their screening protocol. Those that had not considered SCD-E indicated they were unlikely to change their screening protocol when presented with current SCD-E. CONCLUSION:: The majority (62%) of A5DI institutions include ECG and/or echocardiography as part of their cardiovascular screening of all athletes, increasing to 78% when specifically analyzing male basketball athletes. CLINICAL RELEVANCE:: A5DI institutions, presumably with greater resources, have largely implemented more intensive cardiovascular screening than just history and physical for all student-athletes and specifically for men's basketball-the athlete group at greatest risk. PMID- 29792783 TI - Phylogenetic studies in Genabea, Myrmecocystis, and related genera. AB - A multigene phylogenetic analysis of Genabea, Myrmecocystis, and related genera in Pyronemataceae was conducted to establish genetically supported generic limits. The nuc rDNA 28S gene, translation elongation factor 1-alpha gene (TEF1), and RNA polymerase II second-largest subunit gene (RPB2) significantly supported the monophyly of several distinct genera of hypogeous Pyronemataceae. The genetic identity of Genabea fragilis is established, and the new species Genabea hyalospora, G. urbana, Myrmecocystis mediterranea, and M. microspora are proposed to accommodate undescribed lineages. Two rare species, M. sphaerospora and M. spinospora, are tentatively identified based on collections that are morphologically similar to the original descriptions. The genus Genea was found to be monophyletic, except for G. cazaresii, which is nested among epigeous species of Humaria. The new combination Humaria cazaresii is proposed to accommodate this species. PMID- 29792784 TI - Xylaria karyophthora: a new seed-inhabiting fungus of Greenheart from Guyana. AB - In 2010-2011, a Xylaria sp. was documented growing from seeds of both Chlorocardium rodiei and Chlorocardium venenosum, a commercially valuable timber in Guyana. We conducted extensive surveys in 2015-2016, where this Xylaria sp. was observed fruiting from ca. 80% of dispersed seeds in both natural and logged forests in the Upper Demerara-Berbice, Potaro-Siparuni, and the Cuyuni-Mazaruni districts of central Guyana. Species of Xylaria are ascomycetous fungi generally characterized by black, carbonaceous, multiperitheciate ascoma commonly found growing on dead wood. Combined teleomorphic and molecular data indicate that the fungus represents a novel species, described here as Xylaria karyophthora. PMID- 29792785 TI - Two cases of combined patellar tendon avulsion from the tibia and patella. AB - Avulsion fractures of the inferior pole of the patella and proximal tibial apophysis are independently rare injuries. They occur in children due to the relative weakness of the apophyseal cartilage compared to the ligaments and tendons. The combination of these two fractures, is exceedingly rare, with only a few previously described cases in the literature. Due to the infrequent presentation of this injury, careful examination and consideration of advanced imaging is important for diagnosis and preoperative planning. Here we present two cases of combined sleeve fractures of the inferior pole of the patella and tibial apophysis, with discussion of the pathophysiology, classification, identification and management of the injury. PMID- 29792787 TI - [Study and Preliminary Evaluation for Established of Medical Device Software Model]. AB - Based on common software quality evaluation model, this paper explores medical device softwares model established in the basis of the information transmission form. Applying this model, a medical device software evaluation principle has been established, and two different existing forms of medical device software are verified. PMID- 29792788 TI - [Advice on Data Analysis Methods for Clinical Trials of Medical Devices]. AB - This paper provides an overview on data analysis of medical devices undergoing clinical trials during medical device evaluation. It reports some common questions occurred in study design phase and data analysis phase. Then the paper proposes some advice on data analysis methods for different types of products, which may provide technical references for reviewers and clinical data analysts. PMID- 29792786 TI - Imageless navigation total hip arthroplasty - an evaluation of operative time. AB - INTRODUCTION: Imageless navigation has been successfully integrated in knee arthroplasty but its effectiveness in total hip arthroplasty (THA) has been debated. It has consistently been shown that navigation adds significant time and cost to the operation. Further, the relative success of traditional hip replacements has impeded the adoption of new techniques. METHODS: We compared the operative time between fifty total hip replacements with and without the use of imageless navigation by a single senior surgeon in a retrospective study. We employed standard statistical tools to compare the two methods. A correlation based analysis was used to delimit the "learned" phase of imageless navigation to make comparisons meaningful. RESULTS: Contrary to what has previously been reported, there was no significant difference between operative time in navigated, when compared to traditional operations (p = 0.498). Only fourteen operations were required to delimit the learning phase of this operation. DISCUSSION: This is the first study that demonstrates no added operative time when using imageless navigation in THA, achieved with an improved workflow. The results also demonstrate a very reasonable learning curve. PMID- 29792789 TI - [Implementation of Heterogeneous Data Sharing in Regional Medical Treatment Based on HL7 Middleware]. AB - This paper introduces the current situation of the development of regional medical information in our country, analyzes the problem of heterogeneous data sharing, and tries to realize the heterogeneous information sharing by middleware based on HL7. PMID- 29792790 TI - [Development of Modern Medical Equipment Management System Based on Web]. AB - Under the concept of Internet+, this paper proposed modern medical equipment management system, which could satisfy our hospital and also agree with the evaluation of 3A hospital. The system can monitor, analyze and effectively manage the whole life of the equipment that included assembly, use, maintenance, update and rejection. The system mainly includes eleven modules that are equipment management, repair management, online-repair management, PM management, metering management, benefit analysis, guarantee management, supporter management, barcode management, inventory management and inspection management. The system could help to manage medical equipment effectively and optimize resource a location. PMID- 29792791 TI - [An Algorithm to Eliminate Power Frequency Interference in ECG Using Template]. AB - Researching an algorithm to eliminate power frequency interference in ECG. The algorithm first creates power frequency interference template, then, subtracts the template from the original ECG signals, final y, the algorithm gets the ECG signals without interference. Experiment shows the algorithm can eliminate interference effectively and has none side effect to normal signal. It's efficient and suitable for practice. PMID- 29792792 TI - Per-oral Endoscopic Myotomy (POEM): A safe and effective treatment for achalasia in geriatricpatients AB - Background: Esophageal achalasia is a primary motor disorder of the esophagus characterized by impair relaxation of the lower esophageal sphincter and absent of esophageal peristalsis. Per-oral endoscopic myotomy is an alternative treatment to surgical Heller myotomy in patients over 65 years old. The aim of this paper was to describe the results of peroral endoscopic myotomy (POEM) or the treatment of achalasia in geriatric patients. Methods: We included patients over 65 years old with POEM, from retrospective cohort review, in which POEM was performed with a standardized technique in our department. Results: 12 patients were included, the procedure was successful in 98% of patients, minor adverse events occurred without mortality. Conclusions: POEM is a safe and effective technique for the treatment of achalasia, the results of the study are similar to those reported in the literature. PMID- 29792793 TI - [Rationalized Upgrade of Endoscopy Center 's Sterilization Equipment] AB - Objective: To adapt to hospital's modernized construction, we took effect measures to ameliorate disinfection procedure and increase disinfection efficiency for Electronic Endoscopy. Methods: Through confirming the character of disinfection procedure for Electronic Endoscopy in conjunction with infection controlling, we investigated the practical administrative mode in hospital for disinfection procedure of Electronic Endoscopy. Results: After constantly ameliorating administrative mode for disinfection procedure, the disinfection efficiency under its supervision was significantly increased. Conclusion: Reasonable administration and region partition of Electronic Endoscopy disinfection could improve disinfection efficiency in hospital, thus ensuring clinical demand for Endoscopy Center and promoting sustainable development of Department of Internal Medicine. PMID- 29792794 TI - Healthcare-associated infections: Appropriate empirical antibiotic treatment AB - Background: Health-care Associated Infections (HAI) are one of the main causes of death in critically ill patients. The aim of this paper is to establish an appropriate empirical antibiotic treatment for the main HAI in an Intensive Care Unit(ICU). Methods: A retrospective, observational, descriptive and analytical study of the culture results from January, 2014 to December, 2015. The causative microorganisms were identified, as well as sensitivity and antibiotic resistance. Results: Of the three main HAI in the ICU were Ventilator Associated Pneumonia (VAP), whose most common germs were methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa; Urinary Tract Infection Associated with Urinary Catheter (IVU-CU), Escherichia coli BLEE and Pseudomonas aeruginosa were isolated in 70%, and 56% of the bloodstream infections of the germs that caused this infection were three, the most frequent being Escherichia coli, followed by Klebsiella oxytoca and methicillin-resistant Staphylococcus aureus. Conclusions: VAP was the most frequent HAI and resistant methicillin Staphylococcus aureus was the most prevalent in this type of infection. The proposed empiric antibiotic treatment was as follows: VAP (vancomycin plus amikacin plus meropenem), IVU-CU (meropenem) and STIs (vancomycin plus cefepime). PMID- 29792795 TI - Tuning the Morphology of Nanostructured Peptide Films by the Introduction of a Secondary Structure Conformational Constraint: A Case Study of Hierarchical Self Assembly. AB - Peptide self-assembly is ubiquitous in nature. It governs the organization of proteins, controlling their folding kinetics and preserving their structural stability and bioactivity. In this connection, model oligopeptides may give important insights into the molecular mechanisms and elementary forces driving the formation of supramolecular structures. In this contribution, we show that a single residue substitution, that is, Aib (alpha-aminoisobutyric acid) in place of Ala at position 4 of an -(l-Ala)5-homo-oligomer, strongly alters the aggregation process. In particular, this process is initiated by the formation of small peptide clusters that promote aggregation on the nanometer scale and, through a hierarchical self-assembly, lead to mesoscopic structures of micrometric dimensions. Furthermore, we show that the use of the well-established Langmuir-Blodgett technique represents an effective strategy for coating extended areas of inorganic substrates by densely packed peptide layers, thus paving the way for application of peptide films as templates for biomineralization, biocompatible coating of surfaces, and scaffolds for tissue engineering. PMID- 29792796 TI - Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range. AB - Nano-liquid chromatography (nLC)-nanoelectrospray (NSI) is one of the cornerstones of mass-spectrometry-based bioanalytics. Nevertheless, the application of nLC is not yet prevalent in lipid analyses. In this study, we established a reproducible nLC separation for global lipidomics and describe the merits of using such a miniaturized system for lipid analyses. In order to enable comprehensive lipid analyses that is not restricted to specific lipid classes, we particularly optimized sample preparation conditions and reversed-phase separation parameters. We further benchmarked the developed nLC system to a commonly used high flow HPLC/ESI MS system in terms of lipidome coverage and sensitivity. The comparison revealed an intensity gain between 2 and 3 orders of magnitude for individual lipid classes and an increase in the linear dynamic range of up to 2 orders of magnitude. Furthermore, the analysis of the yeast lipidome using nLC/NSI resulted in more than a 3-fold gain in lipid identifications. All in all, we identified 447 lipids from the core phospholipid lipid classes (PA, PE, PC, PS, PG, and PI) in Saccharomyces cerevisiae. PMID- 29792797 TI - Determination of a Focused Mini Kinase Panel for Early Identification of Selective Kinase Inhibitors. AB - We analyzed an extensive data set of 3000 Janssen kinase inhibitors (spanning some 40 therapeutic projects) profiled at 414 kinases in the DiscoverX KINOME scan to better understand the necessity of using such a full kinase panel versus simply profiling one's compound at a much smaller number of kinases, or mini kinase panel (MKP), to assess its selectivity. To this end, we generated a series of MKPs over a range of sizes and of varying kinase membership using Monte Carlo simulations. By defining the kinase hit index (KHI), we quantified a compound's selectivity based on the number of kinases it hits. We find that certain combinations (rather than a random selection) of kinases can result in a much lower average error. Indeed, we identified a focused MKP with a 45.1% improvement in the average error (compared to random) that yields an overall correlation of R2 = 0.786-0.826 for the KHI compared to the full kinase panel value. Unlike using a full kinase panel, which is both time and cost restrictive, a focused MKP is amenable to the triaging of all early stage compounds. In this way, promiscuous compounds are filtered out early on, leaving the most selective compounds for lead optimization. PMID- 29792798 TI - Structural Analysis of Phospholipid Using Hydrogen Abstraction Dissociation and Oxygen Attachment Dissociation in Tandem Mass Spectrometry. AB - Gas-phase hydrogen radicals were introduced into a quadrupole ion trap containing singly charged phospholipids to obtain structural fragmentation patterns in tandem mass spectrometry (MS/MS). Saturated and unsaturated phosphatidylcholines were used as a model phospholipid, whose chain-length ranges between 16 and 24. The MS/MS spectrum yielded a continuous series of fragment ions with a mass difference of 14 Da, representing the saturated fatty acyl chains. The fragment ions corresponding to the double-bond position within a single fatty acyl chain showed a characteristic mass difference of 12 Da. The detection of these diagnostic product ions enabled the structural analysis of double-bond isomers of phospholipids. To further investigate the potential of radical-induced dissociation for the isomeric analysis of phospholipids, gas-phase hydroxyl radicals, and triplet oxygen atoms were employed in tandem mass spectrometry. The methylene bridges adjacent to the double-bond positions were selectively dissociated, accompanied by oxidation of the double bonds. Tandem mass spectrometry incorporating multiple radical species facilitates the structural analysis of isomeric phospholipids. PMID- 29792799 TI - In Vivo Evaluation of Reduction-Responsive Alendronate-Hyaluronan-Curcumin Polymer-Drug Conjugates for Targeted Therapy of Bone Metastatic Breast Cancer. AB - Many cancers, such as human breast cancer and lung cancer, easily metastasize to bones, leading to the formation of secondary tumors in advanced stages. On the basis of the CD44-targeted effect of oHA and the bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nanomicelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction. The CUR-loaded ALN-oHA-S-S-CUR micelles markedly inhibited the tumor growth. So the CUR-loaded ALN-oHA-S-S-CUR micelles constitute a promising drug delivery system for bone tumor therapy. PMID- 29792800 TI - Effects of Enhanced Flexibility and Pore Size Distribution on Adsorption-Induced Deformation of Mesoporous Materials. AB - Here, we present a new model of adsorption-induced deformation of mesoporous solids. The model is based on a simplified version of local density functional theory in the framework of solvation free energy. Instead of density, which is treated as constant here, we used film thickness and pore radius as order parameters. This allows us to obtain a self-consistent system of equations describing simultaneously the processes of gas adsorption and adsorbent deformation, as well as conditions for capillary condensation and evaporation. In the limit of infinitely rigid pore walls, when the film becomes several monolayers thick, the model reduces to the well-known Derjaguin-Broekhoff-de Boer theory for pores with cylindrical geometry. We have investigated the effects of enhanced flexibility of the solid as well as the influence of pore size distribution on the adsorption/deformation process. The formulation of the theory allows to determine the average pore size and its width from the desorption branch of the strain isotherm only. The model reproduces the nonmonotonic behavior of the strain isotherm at low relative pressure. Furthermore, we discuss the effect of rigidity of the adsorbent on the pore size distribution, showing qualitatively different results of the adsorption isotherms for rigid and highly flexible materials, in particular, the shift of evaporation pressure to lower values and the absence of a limiting value of the loading at high relative pressure. We also discuss the results of the theory with respect to experimental data obtained from the literature. PMID- 29792802 TI - The Anti-Biofouling Properties of Superhydrophobic Surfaces are Short-Lived. AB - Superhydrophobic surfaces are present in nature on the leaves of many plant species. Water rolls on these surfaces, and the rolling motion picks up particles including bacteria and viruses. Man-made superhydrophobic surfaces have been made in an effort to reduce biofouling. We show here that the anti-biofouling property of a superhydrophobic surface is due to an entrapped air-bubble layer that reduces contact between the bacteria and the surface. Further, we showed that prolonged immersion of superhydrophobic surfaces in water led to loss of the bubble-layer and subsequent bacterial adhesion that unexpectedly exceeded that of the control materials. This behavior was not restricted to one particular type of material but was evident on different types of superhydrophobic surfaces. This work is important in that it suggests that superhydrophobic surfaces may actually encourage bacterial adhesion during longer term exposure. PMID- 29792801 TI - Development of a Novel Sulfoxide-Containing MS-Cleavable Homobifunctional Cysteine-Reactive Cross-Linker for Studying Protein-Protein Interactions. AB - Cross-linking mass spectrometry (XL-MS) has become an emerging technology for defining protein-protein interactions (PPIs) and elucidating architectures of large protein complexes. Up to now, the most widely used cross-linking reagents target lysines. Although such reagents have been successfully applied to map PPIs at the proteome-wide scale, comprehensive PPI profiling would require additional cross-linking chemistries. Cysteine is one of the most reactive amino acids and an attractive target for cross-linking owing to its unique role in protein structures. Although sulfhydryl-reactive cross-linkers are commercially available, their applications in XL-MS studies remain sparse, likely due to the difficulty in identifying cysteine cross-linked peptides. Previously, we developed a new class of sulfoxide-containing MS-cleavable cross-linkers to enable fast and accurate identification of cross-linked peptides using multistage tandem mass spectrometry (MS n). Here, we present the development of a new sulfoxide-containing MS-cleavable homobifunctional cysteine-reactive cross linker, bismaleimide sulfoxide (BMSO). We demonstrate that BMSO-cross-linked peptides display the same characteristic fragmentation pattern during collision induced dissociation (CID) as other sulfoxide-containing MS-cleavable cross linked peptides, thus permitting their simplified analysis and unambiguous identification by MS n. Additionally, we show that BMSO can complement amine- and acidic-residue-reactive reagents for mapping protein-interaction regions. Collectively, this work not only enlarges the toolbox of MS-cleavable cross linkers with diverse chemistries, but more importantly expands our capacity and capability of studying PPIs in general. PMID- 29792803 TI - Macroporous-Enabled Highly Deformable Layered Hydrogels with Designed pH Response. AB - Environment-responsive hydrogel structures are of great interest in materials research and have a wide range of applications. By using a flow lithography technique, we report a one-step and high-throughput fabrication method for the synthesis of highly pH-responsive hydrogels with designed shape transformations. In this method, heterogeneous hydrogels with porous and nonporous layers are synthesized using a single UV exposure in a microfluidic channel. During the UV polymerization, the porous layers, which are formed by using polymerization induced phase separation (PIPS), significantly increase the swelling capability and enhance the swelling rate of the hydrogels. Because the flow-lithography approach allows various patterns of porous/nonporous layers with great control and enables the simple integration of PIPS, resultant layered hydrogels show extraordinary deformations with desired pH response. More importantly, our fabrication approach can not only make 2D deformation of hydrogel structures such as bending but also can achieve 3D structural deformation such as helical and buckling structures, enabled by nonuniform UV polymerization we developed. PMID- 29792804 TI - Total Synthesis of (+/-)-Crinane from 6,6-Dibromobicyclo[3.1.0]hexane Using a 5- exo- trig Radical Cyclization Reaction to Assemble the C3a-Arylated Perhydroindole Substructure. AB - Crinane embodies the tetracyclic framework associated with some of the most common Amaryllidaceae alkaloids. It has now been prepared in 10 steps from 6,6 dibromobicyclo[3.1.0]hexane (2). The initial step involves the thermally induced electrocyclic ring opening of cyclopropane 3 and capture of the resulting pi allyl cation with benzylamine to give an allylic amine that is readily elaborated to the 3 degrees -amine 10. This last compound was engaged in a 5- exo- trig free radical cyclization reaction to give the C3a-arylated perhydroindole 11. Compound 11 was then converted, over two steps, into (+/-)-crinane, the hydrochloride salt of which has been subjected to single-crystal X-ray analysis. PMID- 29792805 TI - Cheminformatic Insight into the Differences between Terrestrial and Marine Originated Natural Products. AB - This is a new golden age for drug discovery based on natural products derived from both marine and terrestrial sources. Herein, a straightforward but important question is "what are the major structural differences between marine natural products (MNPs) and terrestrial natural products (TNPs)?" To answer this question, we analyzed the important physicochemical properties, structural features, and drug-likeness of the two types of natural products and discussed their differences from the perspective of evolution. In general, MNPs have lower solubility and are often larger than TNPs. On average, particularly from the perspective of unique fragments and scaffolds, MNPs usually possess more long chains and large rings, especially 8- to 10-membered rings. MNPs also have more nitrogen atoms and halogens, notably bromines, and fewer oxygen atoms, suggesting that MNPs may be synthesized by more diverse biosynthetic pathways than TNPs. Analysis of the frequently occurring Murcko frameworks in MNPs and TNPS also reveals a striking difference between MNPs and TNPs. The scaffolds of the former tend to be longer and often contain ester bonds connected to 10-membered rings, while the scaffolds of the latter tend to be shorter and often bear more stable ring systems and bond types. Besides, the prediction from the naive Bayesian drug likeness classification model suggests that most compounds in MNPs and TNPs are drug-like, although MNPs are slightly more drug-like than TNPs. We believe that MNPs and TNPs with novel drug-like scaffolds have great potential to be drug leads or drug candidates in drug discovery campaigns. PMID- 29792806 TI - Fate of Fluorescence Labels-Their Adsorption and Desorption Kinetics to Silver Nanoparticles. AB - Silver nanoparticles are among the most widely used and produced nanoparticles. Because of their frequent application in consumer products, the assessment of their toxicological potential has seen a renewed importance. A major difficulty is the traceability of nanoparticles in in vitro and in vivo experiments. Even if the particles are labeled, for example, by a fluorescent marker, the dynamic exchange of ligands often prohibits their spatial localization. Our study provides an insight into the adsorption and desorption kinetics of two different fluorescent labels on silver nanoparticles with a core radius of 3 nm by dynamic light scattering, small-angle X-ray scattering, and fluorescence spectroscopy. We used BSA-FITC and tyrosine as examples for common fluorescent ligands. It is shown that the adsorption of BSA-FITC takes at least 3 days, whereas tyrosine adsorbs immediately. The quantitative amount of stabilizer on the particle surface was determined by fluorescence spectroscopy and revealed that the particles are stabilized by a monolayer of BSA-FITC (corresponding to 20 +/- 9 molecules), whereas tyrosine forms a multilayered structure consisting of 15900 +/- 200 molecules. Desorption experiments show that the BSA-FITC-stabilized particles are ideally suited for application in in vitro and in vivo experiments because the ligand desorption takes several days. Depending on the BSA concentration in the particles surroundings, the rate constant is k = 0.2 per day or lower when applying first order kinetics, that is, 50% of the BSA-FITC molecules are released from the particle's surface within 3.4 days. For illustration, we provide a first application of the fluorescence-labeled particles in an uptake study with two different commonly used cell lines, the human liver cell model HepG2 and the human intestinal cell model of differentiated Caco-2 cells. PMID- 29792807 TI - Micelles Protect Intact Metallo-supramolecular Block Copolymer Complexes from Solution to Gas Phase during Electrospray Ionization. AB - Supramolecular diblock copolymers using metal-ligand coordination can be synthesized under ambient conditions by delicate design of the end groups of the homopolymer chains. However, mass spectrometric analysis of such metallo supramolecular copolymers is challenging. One of the reasons is the nonpolarity of the polymer chains, making it hard to disperse the complexes in electrospray ionization (ESI)-friendly environments. The other difficulty is the noncovalent nature of such copolymers, which is easily disrupted during the ionization. Here, we demonstrate that the intact metallo-supramolecular diblock copolymers can be maintained sufficiently during the ESI process in aqueous solution within micelles. The high-resolution mass spectrometric evidence revealed that the surfactant molecules effectively protect the noncovalent binding of the complexes into gaseous ions. Intriguingly, surfactant molecules were sufficiently detached away from the copolymer complexes, giving unambiguous mass spectra that were predominated by intact diblock copolymers. This ESI-based approach allowed us to investigate the relative bond strengths of metal-to-ligand complexation using collision-induced dissociation (CID) in the ion trap mass spectrometry. Conformational features and collision cross sections of the copolymers were thus obtained using subsequent ion mobility spectrometry mass spectrometry (IMS-MS). Remarkable environment-dependent conformations of the denoted diblock copolymers were found using this mass spectrometric platform. PMID- 29792808 TI - Eradication of Established Tumors by Chemically Self-Assembled Nanoring Labeled T Cells. AB - Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the nongenetic modification of T cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human epithelial cell adhesion molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells. The alphaEpCAM/alphaCD3 PARs were found to stably bind T cells for >4 days, and treating EpCAM+ MCF-7 breast cancer cells with alphaEpCAM/alphaCD3 PAR-functionalized T cells resulted in the induction of IL-2, IFN-gamma, and MCF-7 cytotoxicity. Furthermore, an orthotopic breast cancer model validated the ability of alphaEpCAM/alphaCD3 PAR therapy to direct T cell lytic activity toward EpCAM+ breast cancer cells in vivo, leading to tumor eradication. In vivo biodistribution studies demonstrated that PAR-T cells were formed in vivo and persist for over 48 h with rapid accumulation in tumor tissue. Following PAR treatment, the production of IL-2, IFN-gamma, IL-6, and TNF-alpha could be significantly reduced by an infusion of clinically relevant concentrations of the FDA-approved antibiotic, trimethoprim, signaling pharmacologic PAR deactivation. Importantly, CSANs did not induce naive T cell activation and thus exhibit a limited potential to induce naive T cell anergy. In addition, murine immunogenicity studies demonstrated that CSANs do not induce a significant antibody response nor do they activate splenic cells. Collectively, our results demonstrate that bispecific CSANs are able to nongenetically generate reversibly modified T cells that are capable of eradicating targeted solid tumors. PMID- 29792809 TI - Thionine Self-Assembled Structures on Graphene: Formation, Organization, and Doping. AB - The association of organic molecules with two-dimensional (2D) materials, creating hybrid systems with mutual influences, constitutes an important testbed for both basic science self-assembly studies and perspective applications. Following this concept, in this work, we show a rich phenomenology that is involved in the interaction of thionine with graphene, leading to a hybrid material formed by well-organized self-assembled structures atop graphene. This composite system is investigated by atomic force microscopy, electric transport measurements, Raman spectroscopy, and first principles calculations, which show (1) an interesting time evolution of thionine self-assembled structures atop graphene; (2) a highly oriented final molecular assembly (in accordance with the underlying graphene surface symmetry); and (3) a strong n-type doping effect introduced in graphene by thionine. The nature of the thionine-substrate interaction is further analyzed in experiments using mica as a polar substrate. The present results may help pave the way to achieve tailored 2D material hybrid devices via properly chosen molecular self-assembly processes. PMID- 29792810 TI - Optogenetic Inhibition of Galphaq Protein Signaling Reduces Calcium Oscillation Stochasticity. AB - As fast terminators of G-protein coupled receptor (GPCR) signaling, regulators of G-protein signaling (RGS) serve critical roles in fine-tuning second messenger levels and, consequently, cellular responses to external stimuli. Here, we report the creation of an optogenetic RGS2 (opto-RGS2) that suppresses agonist-evoked calcium oscillations by the inactivation of Galphaq protein. In this system, cryptochrome-mediated heterodimerization of the catalytic RGS2-box with its N terminal amphipathic helix reconstitutes a functional membrane-localized complex that can dynamically suppress store-operated release of calcium. Engineered opto RGS2 cell lines were used to establish the role of RGS2 as a key inhibitory feedback regulator of the stochasticity of the Galphaq-mediated calcium spike timing. RGS2 reduced the stochasticity of carbachol-stimulated calcium oscillations, and the feedback inhibition was coupled to the global calcium elevation by calmodulin/RGS2 interactions. The identification of a critical negative feedback circuit exemplifies the utility of optogenetic approaches for interrogating RGS/GPCR biology and calcium encoding principles through temporally precise molecular gain-of-function. PMID- 29792811 TI - Tandem Mass Spectrometry of Peptide Ions by Microwave Excited Hydrogen and Water Plasmas. AB - A thermal cracking cell that served as the atomic hydrogen source for hydrogen attachment/abstraction dissociation (HAD) analysis has an intrinsic problem to produce a beam of atoms reactive against heated tungsten capillary. A plasma excited by 2.45 GHz microwave discharge can deliver reactive species to a quadrupole ion trap confining analyte ions without excessive heating of the radical source components. The radical (H*) production performance of the developed source was evaluated by optical emission spectroscopy and H* attachment reaction to fullerene ions. The source exhibited the H* attachment rate as high as a thermal cracking source forming H* in the high temperature tungsten capillary to induce fragmentation processes preserving post-translational modifications. Water vapor was introduced to the source to confirm the stability to generate oxygen containing radicals, which were found present in the water vapor plasma together with atomic hydrogen. Injection of radicals from a water vapor plasma successfully dissociated peptide ions to c-/z- and a-/x-type ions as the case of HAD induced by a thermal cracking cell. PMID- 29792813 TI - Metabolomics Reveals the Molecular Mechanisms of Copper Induced Cucumber Leaf ( Cucumis sativus) Senescence. AB - Excess copper may disturb plant photosynthesis and induce leaf senescence. The underlying toxicity mechanism is not well understood. Here, 3-week-old cucumber plants were foliar exposed to different copper concentrations (10, 100, and 500 mg/L) for a final dose of 0.21, 2.1, and 10 mg/plant, using CuSO4 as the Cu ion source for 7 days, three times per day. Metabolomics quantified 149 primary and 79 secondary metabolites. A number of intermediates of the tricarboxylic acid (TCA) cycle were significantly down-regulated 1.4-2.4 fold, indicating a perturbed carbohydrate metabolism. Ascorbate and aldarate metabolism and shikimate-phenylpropanoid biosynthesis (antioxidant and defense related pathways) were perturbed by excess copper. These metabolic responses occur even at the lowest copper dose considered although no phenotype changes were observed at this dose. High copper dose resulted in a 2-fold increase in phytol, a degradation product of chlorophyll. Polyphenol metabolomics revealed that some flavonoids were down-regulated, while the nonflavonoid 4-hydroxycinnamic acid and trans-2 hydroxycinnamic acid were significantly up-regulated 4- and 26-fold compared to the control. This study enhances current understanding of copper toxicity to plants and demonstrates that metabolomics profiling provides a more comprehensive view of plant responses to stressors, which can be applied to other plant species and contaminants. PMID- 29792812 TI - Ultralow Damping in Nanometer-Thick Epitaxial Spinel Ferrite Thin Films. AB - Pure spin currents, unaccompanied by dissipative charge flow, are essential for realizing energy-efficient nanomagnetic information and communications devices. Thin-film magnetic insulators have been identified as promising materials for spin-current technology because they are thought to exhibit lower damping compared with their metallic counterparts. However, insulating behavior is not a sufficient requirement for low damping, as evidenced by the very limited options for low-damping insulators. Here, we demonstrate a new class of nanometer-thick ultralow-damping insulating thin films based on design criteria that minimize orbital angular momentum and structural disorder. Specifically, we show ultralow damping in <20 nm thick spinel-structure magnesium aluminum ferrite (MAFO), in which magnetization arises from Fe3+ ions with zero orbital angular momentum. These epitaxial MAFO thin films exhibit a Gilbert damping parameter of ~0.0015 and negligible inhomogeneous linewidth broadening, resulting in narrow half width at half-maximum linewidths of ~0.6 mT around 10 GHz. Our findings offer an attractive thin-film platform for enabling integrated insulating spintronics. PMID- 29792814 TI - Perspectives of a myosin motor activator agent with increased selectivity. AB - Clinical treatment of heart failure is still not fully solved. A novel class of agents, the myosin motor activators, acts directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. Omecamtiv mecarbil, the lead molecule of this group, is now in human phase 3 displaying promising clinical performance. However, omecamtiv mecarbil is not selective to myosin, because it readily binds to and activates cardiac ryanodine receptors (RyR-2), an effect that may cause complications in case of overdose. In this study, in silico analysis was performed to investigate the docking of omecamtiv mecarbil and other structural analogues to cardiac myosin heavy chain and RyR-2 to select the structure that has a higher selectivity to myosin over RyR-2. In silico docking studies revealed that omecamtiv mecarbil has comparable affinity to myosin and RyR-2: the respective Kd values are 0.60 and 0.87 MUmol/L. Another compound, CK-1032100, has much lower affinity to RyR-2 than omecamtiv mecarbil, while it still has a moderate affinity to myosin. It was concluded that further research starting from the chemical structure of CK-1032100 may result a better myosin activator burdened probably less by the RyR-2 binding side effect. It also is possible, however, that the selectivity of omecamtiv mecarbil to myosin over RyR-2 cannot be substantially improved, because similar moieties seem to be responsible for the high affinity to both myosin and RyR-2. PMID- 29792815 TI - Molecular Mechanisms of Fast Neurotransmitter Release. AB - This review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca2+-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity. PMID- 29792816 TI - The Physics of the Metaphase Spindle. AB - The assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge. PMID- 29792817 TI - Macroscopic Theory for Evolving Biological Systems Akin to Thermodynamics. AB - We present a macroscopic theory to characterize the plasticity, robustness, and evolvability of biological responses and their fluctuations. First, linear approximation in intracellular reaction dynamics is used to demonstrate proportional changes in the expression of all cellular components in response to a given environmental stress, with the proportion coefficient determined by the change in growth rate as a consequence of the steady growth of cells. We further demonstrate that this relationship is supported through adaptation experiments of bacteria, perhaps too well as this proportionality is held even across cultures of different types of conditions. On the basis of simulations of cell models, we further show that this global proportionality is a consequence of evolution in which expression changes in response to environmental or genetic perturbations are constrained along a unique one-dimensional curve, which is a result of evolutionary robustness. It then follows that the expression changes induced by environmental changes are proportionally reduced across different components of a cell by evolution, which is akin to the Le Chatelier thermodynamics principle. Finally, with the aid of a fluctuation-response relationship, this proportionality is shown to hold between fluctuations caused by genetic changes and those caused by noise. Overall, these results and support from the theoretical and experimental literature suggest a formulation of cellular systems akin to thermodynamics, in which a macroscopic potential is given by the growth rate (or fitness) represented as a function of environmental and evolutionary changes. PMID- 29792818 TI - Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation. AB - Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex ( T3) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy ([Formula: see text]) of a particular protein synthesis system as its current accuracy and the effective selectivity ([Formula: see text]) as [Formula: see text] in the limit of zero ribosomal binding affinity for T3. Intrinsic selectivity ([Formula: see text]), defined as the upper thermodynamic limit of [Formula: see text], is determined by the free energy difference between near-cognate and cognate T3 in the pre-GTP hydrolysis state on the ribosome. [Formula: see text] is much larger than [Formula: see text], suggesting the possibility of a considerable increase in [Formula: see text] and [Formula: see text] at negligible kinetic cost. Induced fit increases [Formula: see text] and [Formula: see text] without affecting [Formula: see text], and aminoglycoside antibiotics reduce [Formula: see text] and [Formula: see text] at unaltered [Formula: see text]. PMID- 29792819 TI - Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II. AB - RNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Recent structural studies of Pol I complexes with transcription initiation factors provided insights into how the polymerase recognizes its specific promoter DNA, how it may open DNA, and how initiation may be regulated. Comparison with the well-studied Pol II initiation system reveals a distinct architecture of the initiation complex and visualizes promoter- and gene class-specific aspects of transcription initiation. On the basis of new structural studies, we derive a model of the Pol I transcription cycle and provide a molecular movie of Pol I transcription that can be used for teaching. PMID- 29792820 TI - Hydrogel-Tissue Chemistry: Principles and Applications. AB - Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three dimensional positioning and/or brain-wide wiring of those very same neurons-even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants-or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout-is stimulating innovation across biology and medicine. PMID- 29792823 TI - Principles of Systems Biology, No. 29. AB - This month: in silico labeling of microscopy images (Christiansen/Finkbeiner), single-cell lineage trees and data integration (Rajewsky, Satija), gene expression (Weinberger/Simpson, Tavazoie, Ameres/Zuber), and signalling networks (Mercer/Wollscheid, Fussenegger). PMID- 29792822 TI - Genetic identity in genebanks: application of the SolCAP 12K SNP array in fingerprinting and diversity analysis in the global in trust potato collection. AB - Breeders rely on genetic integrity of material from genebanks; however, admixture, mislabeling, and errors in original data can occur and be detrimental. Two hundred and fifty accessions, representing paired samples consisting of original mother plants and their in vitro counterparts from the cultivated potato collection at the International Potato Center (CIP) were fingerprinted using the Infinium 12K V2 Potato Array to confirm genetic identity of the accessions and evaluate genetic diversity of the potato collection. Diploid, triploid, and tetraploid accessions were included, representing seven cultivated potato taxa (based on Hawkes, 1990). Fingerprints between voucher mother plants maintained in the field and in vitro clones of the same accession were used to evaluate identity, relatedness, and ancestry using hierarchal clustering and model-based Bayesian admixture analyses. Generally, in vitro and field clones of the same accession grouped together; however, 11 (4.4%) accessions were mismatches genetically, and in some cases the SNP data revealed the identity of the mixed accession. SNP genotypes were used to assess genetic diversity and to evaluate inter- and intraspecific relationships along with determining population structure and hybrid origins. Phylogenetic analyses suggest that the triploids included in this study are genetically similar. Further, some genetic redundancies among individual accessions were also identified along with some putative misclassified accessions. Accessions generally clustered together based on taxonomic classification and ploidy level with some deviations. STRUCTURE analysis identified six populations with significant gene flow among the populations, as well as revealed hybrid taxa and accessions. Overall, the Infinium 12K V2 Potato Array proved useful in confirming identity and highlighting the diversity in this subset of the CIP collection, providing new insights into the accessions evaluated. This study provides a model for genetic identity of plant genetic resources collections as mistakes in conservation of these collections and in genebanks is a reality. For breeders and other users of these collections, confirmed identity is critical, as well as for quality management programs and to provide insights into the accessions evaluated. PMID- 29792821 TI - Exhaustive-exercise-induced oxidative stress alteration of erythrocyte oxygen release capacity. AB - The aim of the present study was to explore the effect of exhaustive running exercise in the oxygen release capacity of rat erythrocytes. Rats were divided into sedentary control, moderate running exercise, and exhaustive running exercise groups. The thermodynamic and kinetic properties of the erythrocyte oxygen release process of the different groups were tested. We also determined the degree of band-3 oxidation and phosphorylation, anion transport activity, and carbonic anhydrase isoform II activity. Biochemical studies suggested that exhaustive running significantly increased oxidative injury parameters in thiobarbituric acid reactive substances and methaemoglobin levels. Furthermore, exhaustive running significantly decreased anion transport activity and carbonic anhydrase isoform II activity. Thermodynamic analysis indicated that erythrocytes oxygen release ability also significantly increased due to elevated 2,3-DPG level after exhaustive running. Kinetic analysis indicated that exhaustive running resulted in significantly decreased T50 value. We presented evidence that exhaustive running remarkably impacted thermodynamic and kinetic properties of RBC oxygen release. In addition, changes in 2,3-DPG levels and band-3 oxidation and phosphorylation could be the driving force for exhaustive-running-induced alterations in erythrocyte oxygen release thermodynamic and kinetic properties. PMID- 29792824 TI - A Host Proteome Atlas of Streptococcus pyogenes Infection. AB - Multiplex quantitative proteomics analysis of mice infected with Group A Streptococcus reveals organ-specific biomarkers of infection. PMID- 29792825 TI - G1/S Transcription Factor Copy Number Is a Growth-Dependent Determinant of Cell Cycle Commitment in Yeast. AB - To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. In rich medium, Whi5, Mbp1, and Swi6 concentrations were independent of cell size, whereas Swi4 concentration doubled in G1 phase, leading to a size-dependent decrease in the Whi5/Swi4 ratio. In small cells, SBF and MBF copy numbers were insufficient to saturate target G1/S promoters, but this restriction diminished as cells grew in size. In poor medium, SBF and MBF subunits, as well as Cln1, were elevated, consistent with a smaller cell size at Start. A mathematical model constrained by sN&B data suggested that size- and nutrient-dependent occupancy of G1/S promoters by SBF/MBF helps set the cell size threshold for Start activation. PMID- 29792827 TI - Reply. PMID- 29792826 TI - Fast-Evolving Human-Specific Neural Enhancers Are Associated with Aging-Related Diseases. AB - The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging related diseases and enhancers acquired after the human-chimpanzee divergence. We report a 5-fold increased evolutionary rate of enhancers that are activated in neural tissues, leading to fixation of ~100 human-specific enhancers potentially under adaptation. These enhancers show prognostic expression levels and correlations with driver genes in cancer, and their nearby genes are enriched in known loci associated with aging-related diseases. Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. PMID- 29792828 TI - Recurrence of Pericardial Mesothelioma Affecting the Myocardium After Pericardial Resection. AB - Primary pericardial mesothelioma represents less than 1% of all malignant mesotheliomas. These tumors are very rare, difficult to diagnose, and have a poor response to established treatments. Common clinical presentations include constrictive symptoms, cardiac tamponade, and cardiac failure. Surgical resection can be curative in early stages and for localized tumors, and pericardiectomy and chemotherapy are often used as palliative approaches. We present the case of a 54 year-old woman who has so far survived 4 years after a primary resection of a pericardial mesothelioma and was referred with myocardial and aortopulmonary window recurrences for further treatment. PMID- 29792829 TI - Alfieri Edge-to-Edge Mitral Valve Repair for All Seasons? PMID- 29792830 TI - Subglottic Resections: How I Teach It. PMID- 29792831 TI - Novel generations of laboratory instruments should not worsen analytical quality: The case of GEM Premier 5000. PMID- 29792832 TI - Sperm DNA fragmentation in the total and vital fractions before and after density gradient centrifugation: Significance in male fertility diagnosis. AB - BACKGROUND: Sperm DNA fragmentation measured by different techniques make comparisons impossible due to lack of standardization. Induction of DNA damage after sperm preparation in the entire fraction has been observed on independent occasions but findings are not consistent. METHODS: Men presenting at a University hospital setup for infertility treatment. DNA damage via TUNEL assay was validated on fresh semen samples, as conventional semen parameters, to reduce variability of results. RESULTS: Sperm motility in neat semen inversely correlated with sperm DNA fragmentation in the total fraction, but, total count, leukocytes and immature germ cells significantly affected the vital fraction. Sperm DNA fragmentation was observed both in normal and subnormal semen samples, but was significantly different in the total fraction of astheno-, asthenoterato- and oligoteratozoospermic men. After density gradient centrifugation, sperm DNA fragmentation increased significantly in the total but decreased in the vital fraction. Advancing male age significantly influenced damage in the total but not in the vital population. CONCLUSIONS: These findings provide opportunities to investigate the significance of the total and the vital fractions both in natural conception and after different assisted reproductive technologies. PMID- 29792834 TI - Improvement of Esthetic, Functional, and Social Well-Being After Orthognathic Surgical Intervention: A Sampling of Postsurgical Patients Over a 10-Year Period From 2007 to 2017. AB - PURPOSE: The objectives of this study were to evaluate the effect of orthognathic surgery on the long-term quality of life of patients who received this treatment and to delineate the common reasons for dissatisfaction. MATERIALS AND METHODS: In this retrospective cohort study, patients who underwent orthognathic surgery were studied. One hundred thirty-two patients who had undergone orthognathic surgery from 2007 to 2017 in the oral and maxillofacial surgery department participated in this study. They were divided based on their dentofacial deformity into those with Class II malocclusion and those with Class III malocclusion. Each participant completed a modified questionnaire used to assess the patient's esthetic, social, and functional abilities after orthognathic surgery. RESULTS: The rate of esthetic improvement in orthognathic surgery patients was 91.7%. No significant difference between male and female patients was found regarding the changes in social, esthetic, and functional aspects before and after orthognathic surgery. Both genders recommended orthognathic surgery for patients with similar problems. One in four patients was dissatisfied with the nasal appearance after the surgical procedure (25.8%). CONCLUSIONS: In this study the patients' satisfaction from the orthognathic surgical procedure was mostly a result of improvements in facial esthetics, followed by psychological well-being and then functional abilities. Most dissatisfaction after the orthognathic surgical procedure was related to nasal appearance. PMID- 29792835 TI - Safety and Efficacy of Outpatient Parotidectomy. AB - PURPOSE: Given the increasing costs of medical care, there has been a shift to outpatient elective surgeries in certain patient populations among all surgical specialties. The goal of this study was to compare the safety and efficacy of outpatient parotidectomy with traditional inpatient parotidectomy. MATERIALS AND METHODS: This is a retrospective chart review of all patients who underwent a parotidectomy at a single tertiary academic center from 2007 through 2017. RESULTS: There were 568 patients who met the inclusion criteria. There was no difference in demographics or patient comorbidities between the inpatient and outpatient groups. There was no increased incidence of postoperative complications or extent of postoperative care in patients who underwent outpatient parotidectomy. On average at the authors' institution, the direct outpatient parotidectomy cost was $1,200 less than the inpatient equivalent. CONCLUSION: Outpatient parotidectomy can be performed safely and cost effectively with no increased risk of complications. PMID- 29792833 TI - Self-diffusion of water-soluble fullerene derivatives in mouse erythrocytes. AB - Self-diffusion of water-soluble fullerene derivative (WSFD) C60[S(CH2)3SO3Na]5H in mouse red blood cells (RBC) was characterized by 1H pulsed field gradient NMR technique. It was found that a fraction of fullerene molecules (~13% of the fullerene derivative added in aqueous RBC suspension) shows a self-diffusion coefficient of (5.5 +/- 0.8).10-12 m2/s, which is matching the coefficient of the lateral diffusion of lipids in the erythrocyte membrane (DL = (5.4 +/- 0.8).10-12 m2/s). This experimental finding evidences the absorption of the fullerene derivative by RBC. Fullerene derivative molecules are also absorbed by RBC ghosts and phosphatidylcholine liposomes as manifested in self-diffusion coefficients of (7.9 +/- 1.2).10-12 m2/s and (7.7 +/- 1.2).10-12 m2/s, which are also close to the lateral diffusion coefficients of (6.5 +/- 1.0).10-12 m2/s and (8.5 +/- 1.3).10-12 m2/s, respectively. The obtained results suggest that fullerene derivative molecules are, probably, fixed on the RBC surface. The average residence time of the fullerene derivative molecule on RBC was estimated as 440 +/- 70 ms. Thus, the pulsed field gradient NMR was shown to be a versatile technique for investigation of the interactions of the fullerene derivatives with blood cells providing essential information, which can be projected on their behavior in-vivo after intravenous administration while screening as potential drug candidates. PMID- 29792836 TI - Medicare in Oral and Maxillofacial Surgery: Disparities in Access Part 1. PMID- 29792837 TI - Total Avulsed Ear Management With Radial Forearm Free Flap. AB - Avulsive injuries to the ear are extremely challenging to treat. The literature documents numerous ways to manage such injuries. This report describes a case of total auricular cartilaginous avulsion that occurred during a motor vehicle accident. The avulsed segment had an ischemia time longer than 8 hours by the time of presentation at the authors' tertiary care facility. The avulsed segment was de-epithelialized and embedded into the volar forearm. After a healing period of 6 months, a radial forearm free flap was harvested and the ear was reconstructed. After ensuring good flap uptake and adequate primary healing, the flap was debulked and reshaped at 4 months after inset. PMID- 29792838 TI - Systemic Solutions in Retinopathy of Prematurity. AB - PURPOSE: To describe a framework for screening and treatment of retinopathy of prematurity (ROP) using telemedicine screening with laser and/or vascular endothelial growth factor inhibitor treatment strategies. DESIGN: Literature review and perspective. METHODS: Review of the literature and the author's experience. RESULTS: Undetermined. CONCLUSIONS: Telemedicine can be deployed on a national basis to provide quaternary-level screening for ROP. At-risk patients for treatment could then be directed to receive either laser photocoagulation or vascular endothelial growth factor inhibitor intravitreal injections followed at a later time by examination under anesthesia, fluorescein angiography, and diode laser photocoagulation as indicated. PMID- 29792839 TI - Patient choice of adjunctive nonpharmacologic pain management during first trimester abortion: a randomized controlled trial. AB - OBJECTIVE: To determine if offering patients a choice of adjunctive nonpharmacologic pain management during first-trimester aspiration abortion results in lower pain scores when compared with standard care. STUDY DESIGN: We enrolled women receiving first-trimester aspiration abortion at the University of Hawaii. We randomized patients to standard care (control) or standard care plus a choice of nonpharmacologic pain management options (intervention). Standard care was ibuprofen 800 mg orally at least 30 min preprocedure, lidocaine paracervical block and anticipatory guidance from the provider. We measured pain on a 100-mm visual analog scale immediately postprocedure with adequate sample size to detect a 20-mm difference in pain scores. RESULTS: Seventy-four women participated in the trial and reported an overall mean pain score of 61.9+/-27.0. Participants in the control and intervention groups reported similar overall mean pain scores (control 60.6+/-28.8, intervention 63.3+/-28.5). We found procedure time, complications, provider-perceived case difficulty and patient satisfaction with pain management to be similar between groups. Providers underestimated participant pain compared to participants' own scores (mean physician estimate of participant pain: 46.3+/-18.5, mean participant pain score: 61.9+/-27.0, p<.01). Intervention group participants most frequently selected ambient music (59%) as the nonpharmacologic intervention. Forty-one percent (15/37) of participants in the intervention group chose more than one nonpharmacologic intervention. CONCLUSIONS: Participants in the control group reported similar pain scores to participants in the intervention group. Procedure time and difficulty were similar between the two groups. IMPLICATIONS: Incorporating patient choice into a nonpharmacologic pain management model did not result in lower pain scores. This approach did increase the patient's visit time. Abortion providers frequently use nonpharmacologic pain management in the United States, and these techniques did not negatively impact patient pain scores in our study. PMID- 29792840 TI - Is pregnancy fatalism normal? An attitudinal assessment among women trying to get pregnant and those not using contraception. AB - OBJECTIVES: To assess factors associated with pregnancy fatalism among U.S. adult women. STUDY DESIGN: I used data from the Change and Consistency in Contraceptive Use study, which collected information from a national sample of 4634 U.S. women aged 18-39 at baseline (59% response rate). I assessed pregnancy fatalism based on agreement with the statement: "It doesn't matter whether I use birth control, when it is my time to get pregnant, it will happen." I compared fatalism among all respondents to fatalism among respondents who were trying to get pregnant and those who did not want to get pregnant but were not using contraception. I used logistic regression to assess associations between nonuse of contraception and pregnancy fatalism at baseline and whether respondents were trying to get pregnant 6 months later. RESULTS: Overall, 36% of the sample expressed some degree of pregnancy fatalism, and proportions were higher for respondents trying to get pregnant (55%) and those not using contraception (57%). The association between pregnancy fatalism and trying to get pregnant was maintained after controlling for other characteristics [odds ratio (OR) 1.4, p=.01], as was the association for nonuse of contraception (OR 2.08, p<.001). Contraceptive nonusers at baseline were more likely than users to be trying to get pregnant 6 months later, especially if they expressed a fatalistic outlook at baseline. CONCLUSIONS: Pregnancy fatalism may be a common outlook among women who are trying to get pregnant. Associations between fatalism and nonuse of contraception may be more complex than previously recognized. IMPLICATIONS: Gaining a better understanding of the dynamics of pregnancy planning might inform our understanding of why some women do not use contraception. PMID- 29792842 TI - Reply by Authors. PMID- 29792841 TI - Decarboxylation of Ang-(1-7) to Ala1-Ang-(1-7) leads to significant changes in pharmacodynamics. AB - The heptapeptide angiotensin (Ang)-(1-7) is part of the beneficial arm of the renin-angiotensin system. Ang-(1-7) has cardiovascular protective effects, stimulates regeneration, and opposes the often detrimental effects of AngII. We recently identified the G protein-coupled receptors Mas and MrgD as receptors for the heptapeptide. Ala1-Ang-(1-7) (Alamandine), a decarboxylated form of Ang-(1 7), has similar vasorelaxant effects, but has been described as only stimulating MrgD. Therefore, this study aimed to characterise the consequences of the lack of the carboxyl group in amino acid 1 on intracellular signalling and to identify the receptor fingerprint for Ala1-Ang-(1-7). In primary endothelial and mesangial cells, Ala1-Ang-(1-7) elevated cAMP concentration. Dose response curves generated with Ang-(1-7) and Ala1-Ang-(1-7) significantly differed from each other, with a much lower EC50 and a bell-shape curve for Ala1-Ang-(1-7). We provided pharmacological proof that both, Mas and MrgD, are functional receptors for Ala1 Ang-(1-7). Consequently, in primary mesangial cells with genetic deficiency in both receptors, the heptapeptide failed to increase cAMP concentration. As we previously described for Ang-(1-7), the Ala1-Ang-(1-7)-mediated cAMP increase in Mas/MrgD-transfected HEK293 cells and primary cells was blocked by the AT2 receptor blocker, PD123319. The very distinct dose-response curves for both heptapeptides could be explained by in silico modelling, electrostatic potential calculations, and an involvement of Galpha i for higher concentrations of Ala1 Ang-(1-7). Our results identify Ala1-Ang-(1-7) as a peptide with specific pharmacodynamic properties and builds the basis for the design of more potent and efficient Ang-(1-7) analogues for therapeutic intervention in a rapidly growing number of diseases. PMID- 29792843 TI - Editorial Comment. PMID- 29792844 TI - Bizarre multilobated myeloma cells mimicking megakaryocytes. PMID- 29792845 TI - Current frontline endocrine treatment options for women with hormone receptor positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced-stage breast cancer. AB - Despite the recent advances in breast cancer early detection and awareness, a significant portion of patients present with an advanced-stage disease and more patients will progress to stage IV despite adequate treatment of their initial early-stage disease. Hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor-2 (HER2)-negative subtype is the commonest among all breast cancer subtypes. The management of the advanced-stage disease of this subtype has evolved significantly over the past few years. The emergence of estrogen receptor down regulators (fulvestrant), mTOR-inhibitors and the recent introduction of CDK4/6 inhibitors, like palbociclib, abemaciclib and ribociclib, has resulted in a significant and a historical improvement in treatment outcomes. In this paper, we review many of the recently reported clinical trials that led to the approval of these new drugs in the first-line settings, along with the current international guidelines. PMID- 29792847 TI - The polymorphisms of ATOH 7, ET-1 and ACE in non-arteritic anterior ischemic optic neuropathy. AB - Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic neuropathy in the elderly. The role of the genetic polymorphisms of Atonal Homolog 7 (ATOH7), Endothelin-1 (ET-1) and Angiotensin Converting Enzyme (ACE) in NAION and the combined effects of the gene-gene and gene-medical comorbidities on NAION were not clear. We conducted a perspective, case-control study. 71 NAION patients and 142 age and sex-matched healthy controls were enrolled. Single nucleotide polymorphisms of ATOH7 (rs1900004), ET-1 (rs5370) and ACE (rs1799752) were identified by polymerase chain reaction (PCR) method and all PCR products were screened with Sanger sequencing. The prevalence of genetic factors in NAION patients were compared to normal people, and assessed in conditional logistic regression models. The modified effects of gene-gene or gene medical comorbidities on NAION development were assessed with a multiplicative model. A significant high risk was found in the T allele of ATOH7 in NAION, with an odds ratio (OR) of 1.55 (P = 0.04). Conditional logistic regression analysis, including diabetes and hypertension, revealed that ATOH7 TT genotype carriers conferred a significantly increased risk of NAION (TT/CC + CT, OR = 3.32, 95% confidence interval (CI) = 1.16-9.53, P = 0.03). Interaction analysis showed that ET-1 (P = 0.01), ACE (P = 0.046) and hypertension (P = 0.02) have modified effects on NAION development. Our results showed that the polymorphism of optic disc associated gene-ATOH7 conferred a significant risk of NAION. Combination of ATOH7 and ET-1, ATOH7 and ACE, as well as ATOH7 and hypertension, increased the susceptibility of NAION. Our data may be useful for NAION predicting. PMID- 29792848 TI - Subthalamic nucleus deep brain stimulation protects neurons by activating autophagy via PP2A inactivation in a rat model of Parkinson's disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum. PD rats were subjected to DBS of the STN (STN-DBS) and the effects on motor symptoms and number of nigral tyrosine hydroxylase-positive (TH+) neurons was examined. We found that STN-DBS improved movement disorder and mitigated the loss of TH+ neurons induced by 6-OHDA. Furthermore, STN-DBS blocked protein phosphatase (PP)2A activation induced by 6-OHDA and led to the phosphorylation of B cell lymphoma (Bcl)-2, thereby increasing its activity. This induced its disassociation from Beclin1, a positive regulator of autophagy, leading to autophagy and inhibition of apoptosis. These findings demonstrate for the first time that STN-DBS could exert neuroprotective effects against 6-OHDA-induced cell injury in PD by inducing autophagy via PP2A inactivation and dissociation of the Bcl-2/Beclin1 complex, thereby providing a molecular basis of STN-DBS neuroprotection for PD. PMID- 29792849 TI - The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid. AB - Monocyte migration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca2+-activated K+ (KCa3.1) channels play an important role in cell migration. However, the role of KCa3.1 channels in mediating monocyte migration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of KCa3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA treated monocytes exhibited increment of the protein levels of KCa3.1 channel and monocyte chemoattractant protein-1 (MCP-1), and the effects were reversed by co incubation of PA with anti-TLR2/4 antibodies or by specific inhibitors of p38 MAPK, or NF-kappaB. In addition, PA increased monocyte migration, which was abolished by a specific KCa3.1 channel blocker, TRAM-34, or KCa3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and KCa3.1 siRNA. These results demonstrate for the first time that PA upregulates KCa3.1 channels through TLR2/4, p38-MAPK and NF-kappaB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of monocytes. PMID- 29792846 TI - Adenosine receptor distribution in Rhesus monkey ocular tissue. AB - Adenosine receptor (ADOR) antagonists, such as 7-methylxanthine (7-MX), have been shown to slow myopia progression in humans and animal models. Adenosine receptors are found throughout the body, and regulate the release of neurotransmitters such as dopamine and glutamate. However, the role of adenosine in eye growth is unclear. Evidence suggests that 7-MX increases scleral collagen fibril diameter, hence preventing axial elongation. This study used immunohistochemistry (IHC) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to examine the distribution of the four ADORs in the normal monkey eye to help elucidate potential mechanisms of action. Eyes were enucleated from six Rhesus monkeys. Anterior segments and eyecups were separated into components and flash-frozen for RNA extraction or fixed in 4% paraformaldehyde and processed for immunohistochemistry against ADORA1, ADORA2a, ADORA2b, and ADORA3. RNA was reverse-transcribed, and qPCR was performed using custom primers. Relative gene expression was calculated using the DeltaDeltaCt method normalizing to liver expression, and statistical analysis was performed using Relative Expression Software Tool. ADORA1 immunostaining was highest in the iris sphincter muscle, trabecular meshwork, ciliary epithelium, and retinal nerve fiber layer. ADORA2a immunostaining was highest in the corneal epithelium, trabecular meshwork, ciliary epithelium, retinal nerve fiber layer, and scleral fibroblasts. ADORA2b immunostaining was highest in corneal basal epithelium, limbal stem cells, iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells and scattered scleral fibroblasts. ADORA3 immunostaining was highest in the iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells, and scleral fibroblasts. Compared to liver mRNA, ADORA1 mRNA was significantly higher in the brain, retina and choroid, and significantly lower in the iris/ciliary body. ADORA2a expression was higher in brain and retina, ADORA2b expression was higher in retina, and ADORA3 was higher in the choroid. In conclusion, immunohistochemistry and RT-qPCR indicated differential patterns of expression of the four adenosine receptors in the ocular tissues of the normal non-human primate. The presence of ADORs in scleral fibroblasts and the choroid may support mechanisms by which ADOR antagonists prevent myopia. The potential effects of ADOR inhibition on both anterior and posterior ocular structures warrant investigation. PMID- 29792850 TI - MicroRNA-182 inhibits HCMV replication through activation of type I IFN response by targeting FOXO3 in neural cells. AB - Human cytomegalovirus (HCMV) has led to kinds of clinical disorders and great morbidity worldwide, such as sensorineural hearing loss (SNHL), mental retardation, and developmental delays in immunocompromised individuals. Congenital HCMV infection is a leading cause of birth defects, primarily manifesting as neurological disorders. Previous studies reported that HCMV has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HCMV infection in neural cells are limited. Here, we reported that a host microRNA, miR-182, was significantly up-regulated by HCMV infection in U-251MG and NPCs cells. Subsequently, our results of in vitro and in vivo experiments demonstrated that miR-182 was a positive regulator of interferon regulatory factor 7 (IRF7) by directly targeting FOXO3, resulting in the induction of IFN-I response and suppression of HCMV replication in neural cells. Taken together, our findings provide detailed molecular mechanisms of the antiviral function of miR-182 against HCMV infection in neural cells, and suggest an intrinsic anti-HCMV therapeutic target. PMID- 29792851 TI - Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease. AB - Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-gamma + and IL-17 + IFN-gamma + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3+ T regulatory cells (Treg) did not differ between sexes. Thus, CD4+ Teff cells/Treg ratio, and IL-17+ T cells/Treg and IFN-gamma + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4+ T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-gamma dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis. PMID- 29792853 TI - Preoperative obstructive sleep apnea screening in gynecologic oncology patients. AB - BACKGROUND: Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events. OBJECTIVE: We sought to estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes. STUDY DESIGN: Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a nonemergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP questionnaire (ie, Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure). All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m2) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes. RESULTS: Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (P < .001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (odds ratio, 3.5; 95% confidence interval, 1.8-4.7; P = .011) and delayed return of bowel function (odds ratio, 2.1; 95% confidence interval, 1.3 4.5; P = .009). CONCLUSION: The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present. PMID- 29792852 TI - Is there a survival advantage in diagnosing endometrial cancer in asymptomatic postmenopausal patients? An Israeli Gynecology Oncology Group study. AB - BACKGROUND: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking. OBJECTIVE: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer. STUDY DESIGN: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared. RESULTS: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37). CONCLUSION: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time. PMID- 29792856 TI - Comparison of the 3-D patterns of the parasympathetic nervous system in the lung at late developmental stages between mouse and chicken. AB - Although the basic schema of the body plan is similar among different species of amniotes (mammals, birds, and reptiles), the lung is an exception. Here, anatomy and physiology are considerably different, particularly between mammals and birds. In mammals, inhaled and exhaled airs mix in the airways, whereas in birds the inspired air flows unidirectionally without mixing with the expired air. This bird-specific respiration system is enabled by the complex tubular structures called parabronchi where gas exchange takes place, and also by the bellow-like air sacs appended to the main part of the lung. That the lung is predominantly governed by the parasympathetic nervous system has been shown mostly by physiological studies in mammals. However, how the parasympathetic nervous system in the lung is established during late development has largely been unexplored both in mammals and birds. In this study, by combining immunocytochemistry, the tissue-clearing CUBIC method, and ink-injection to airways, we have visualized the 3-D distribution patterns of parasympathetic nerves and ganglia in the lung at late developmental stages of mice and chickens. These patterns were further compared between these species, and three prominent similarities emerged: (1) parasympathetic postganglionic fibers and ganglia are widely distributed in the lung covering the proximal and distal portions, (2) the gas exchange units, alveoli in mice and parabronchi in chickens, are devoid of parasympathetic nerves, (3) parasympathetic nerves are in close association with smooth muscle cells, particularly at the base of the gas exchange units. These observations suggest that despite gross differences in anatomy, the basic mechanisms underlying parasympathetic control of smooth muscles and gas exchange might be conserved between mammals and birds. PMID- 29792855 TI - The versatile hippo pathway in oral-maxillofacial development and bone remodeling. AB - The Hippo signaling pathway is implicated in key aspects of cell proliferation, control of organ size, stem cell functions and tumor suppression. Its functions are primarily mediated either through direct effects on transcription factors to influence target gene expression or through crosstalk with other signaling pathways that regulate multiple physiological activities. Studies are revealing Hippo pathway involvement in diverse functions including renewal of intestinal epithelium, promotion of myocardial cell proliferation, cancer suppression, etc. In this review we discuss Hippo pathway signaling in oral-maxillofacial development and bone remodeling under normal and pathological conditions and highlight promising future research directions. PMID- 29792854 TI - Bergmann glial Sonic hedgehog signaling activity is required for proper cerebellar cortical expansion and architecture. AB - Neuronal-glial relationships play a critical role in the maintenance of central nervous system architecture and neuronal specification. A deeper understanding of these relationships can elucidate cellular cross-talk capable of sustaining proper development of neural tissues. In the cerebellum, cerebellar granule neuron precursors (CGNPs) proliferate in response to Purkinje neuron-derived Sonic hedgehog (Shh) before ultimately exiting the cell cycle and migrating radially along Bergmann glial fibers. However, the function of Bergmann glia in CGNP proliferation remains not well defined. Interestingly, the Hh pathway is also activated in Bergmann glia, but the role of Shh signaling in these cells is unknown. In this study, we show that specific ablation of Shh signaling using the tamoxifen-inducible TNCYFP-CreER line to eliminate Shh pathway activator Smoothened in Bergmann glia is sufficient to cause severe cerebellar hypoplasia and a significant reduction in CGNP proliferation. TNCYFP-CreER; SmoF/- (SmoCKO) mice demonstrate an obvious reduction in cerebellar size within two days of ablation of Shh signaling. Mutant cerebella have severely reduced proliferation and increased differentiation of CGNPs due to a significant decrease in Shh activity and concomitant activation of Wnt signaling in SmoCKO CGNPs, suggesting that this pathway is involved in cross-talk with the Shh pathway in regulating CGNP proliferation. In addition, Purkinje cells are ectopically located, their dendrites stunted, and the Bergmann glial network disorganized. Collectively, these data demonstrate a previously unappreciated role for Bergmann glial Shh signaling activity in the proliferation of CGNPs and proper maintenance of cerebellar architecture. PMID- 29792857 TI - TGF-beta plays a vital role in triple-negative breast cancer (TNBC) drug resistance through regulating stemness, EMT and apoptosis. AB - Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-beta) is a multifunctional cytokine. In recent study, it appears that TGF-beta influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected. We used epirubicin to treat MDA-MB-231 (MB-231) cells and found that TGF-beta and breast cancer stem cell markers CD44+CD24- were increased and were dose-dependent of epirubicin. We established drug-resistant cell line from parental MB-231 cells by chronic treatment with low-concentration epirubicin. The MB-231/Epi cell line showed relatively slow growth rate with varied morphology. Transwell assay and drug sensitivity assay revealed that the malignant cell behaviors in terms of migration, invasion and epirubicin-resistant properties were markedly increased in the MB-231/Epi cells. Western blot, immunofluorescence assay, and flow cytometry were used to analyze the expression levels of the breast cancer stem cell markers, CD44 and CD24. Mammospheres assay showed that the stemness of MB 231/Epi was increased compared to their parental cells. Interestingly, MB-231/Epi cells showed different expression levels of apoptosis-related markers: Bcl2, Bax; EMT-related markers E-cadherin, N-cadherin and cell cycle-related marker cyclinD1. These genes have all been shown to be regulated by the TGF-beta pathway. Taken together, our findings suggest that TGF-beta plays a vital role in TNBC epirubicin-resistance through regulating stemness, EMT and apoptosis. PMID- 29792858 TI - Luciferase of the Japanese syllid polychaete Odontosyllis undecimdonta. AB - Odontosyllis undecimdonta is a marine syllid polychaete that produces bright internal and exuded bioluminescence. Despite over fifty years of biochemical investigation into Odontosyllis bioluminescence, the light-emitting small molecule substrate and catalyzing luciferase protein have remained a mystery. Here we describe the discovery of a bioluminescent protein fraction from O. undecimdonta, the identification of the luciferase using peptide and RNA sequencing, and the in vitro reconstruction of the bioluminescence reaction using highly purified O. undecimdonta luciferin and recombinant luciferase. Lastly, we found no identifiably homologous proteins in publicly available datasets. This suggests that the syllid polychaetes contain an evolutionarily unique luciferase among all characterized luminous taxa. PMID- 29792859 TI - Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells. AB - Estrogen drives the development and progression of estrogen receptor (ER) positive breast cancer. However, the detailed mechanism underlying ER-driven carcinogenesis remains unclear despite extensive studies. Previously reports indicated higher expression of long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) in ER-positive breast cancer tissues than in ER negative tissues. However, the functional relevance of MIAT in ER-positive breast cancer tumorigenesis was poorly understood. Here, we investigated the role of lncRNA MIAT in ER-positive breast cancer cells. MIAT was over-expressed in ER positive breast cancer tissues and ER-positive breast cancer cell line MCF-7. Activating estrogen signaling by diethylstilbestrol (DES) led to a dose- and time dependent up-regulation of MIAT in MCF-7 cells that was dependent on ERalpha, as evidenced by ERalpha silencing and pharmacological inhibition using ER antagonist ICI 182780. Silencing MIAT decreased DES-induced MCF-7 cell proliferation while overexpressing MIAT increased MCF-7 cell proliferation. Further mechanistic study identified that MIAT was critical for G1 to S phase cell cycle transition. Taken together, these results suggest that lncRNA MIAT is an estrogen-inducible lncRNA and a key regulator in ER-positive breast cancer cell growth. MIAT could serve as a potential biomarker and promising therapeutic target for ER-positive breast cancer. PMID- 29792860 TI - Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways. AB - Diphenyleneiodonium (DPI) and N-acetyl-l-cysteine (NAC), two widely used anti oxidants, were employed to evaluate the role of oxidative stress in Japanese encephalitis virus (JEV) induced autophagy, stress responses and replication. DPI and NAC exerted opposite effects on ROS levels in JEV infected mouse neuronal cells (Neuro2a), mouse embryonic fibroblasts (MEFs) and human epithelial cells (HeLa). While NAC effectively quenched ROS, DPI enhanced ROS levels, suggesting that DPI induces oxidative stress in JEV infected cells. DPI treatment of JEV infected Neuro2a cells further blocked autophagy induction and activation of all three arms of the ER stress pathway, and, inhibited virus particle release. Autophagy induction in JEV infection has been previously shown to be linked to the activation of XBP1 and ATF6 ER stress sensors. Our data suggests that DPI mediated block of autophagy is a result of inhibition of ER stress responses and is not associated with an anti-oxidative effect. Since DPI has a wide inhibitory potential for all Flavin dependent enzymes, it is likely that the signalling pathways for ER stress and autophagy during JEV infection are modulated by DPI sensitive enzymes. PMID- 29792861 TI - Neuroligin-3 protects retinal cells from H2O2-induced cell death via activation of Nrf2 signaling. AB - Intensified oxidative stress can cause severe damage to human retinal pigment epithelium (RPE) cells and retinal ganglion cells (RGCs). The potential effect of neuroligin-3 (NLGN3) against the process is studied here. Our results show that NLGN3 efficiently inhibited hydrogen peroxide (H2O2)-induced death and apoptosis in human RPE cells and RGCs. H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage in retinal cells were alleviated by NLGN3. NLGN3 activated nuclear-factor-E2-related factor 2 (Nrf2) signaling, enabling Nrf2 protein stabilization, nuclear translocation and expression of key anti-oxidant enzymes (HO1, NOQ1 and GCLC) in RPE cells and RGCs. Further results demonstrate that NLGN3 activated Akt-mTORC1 signaling in retinal cells. Conversely, Akt-mTORC1 inhibitors (RAD001 and LY294002) reduced NLGN3-induced HO1, NOQ1 and GCLC mRNA expression. Significantly, Nrf2 silencing by targeted shRNAs reversed NLGN3-induced retinal cytoprotection against H2O2. We conclude that NLGN3 activates Nrf2 signaling to protect human retinal cells from H2O2. NLGN3 could be further tested as a valuable retinal protection agent. PMID- 29792862 TI - The reason for the low Ca2+-sensitivity of thin filaments associated with the Glu41Lys mutation in the TPM2 gene is "freezing" of tropomyosin near the outer domain of actin and inhibition of actin monomer switching off during the ATPase cycle. AB - The E41K mutation in TPM2 gene encoding muscle regulatory protein beta tropomyosin is associated with nemaline myopathy and cap disease. The mutation results in a reduced Ca2+-sensitivity of the thin filaments and in muscle weakness. To elucidate the structural basis of the reduced Ca2+-sensitivity of the thin filaments, we studied multistep changes in spatial arrangement of tropomyosin (Tpm), actin and myosin heads during the ATPase cycle in reconstituted fibers, using the polarized fluorescence microscopy. The E41K mutation inhibits troponin's ability to shift Tpm to the closed position at high Ca2+, thus restraining the transition of the thin filaments from the "off" to the "on" state. The mutation also inhibits the ability of S1 to shift Tpm to the open position, decreases the amount of the myosin heads bound strongly to actin at high Ca2+, but increases the number of such heads at low Ca2+. These changes may contribute to the low Ca2+-sensitivity and muscle weakness. As the mutation has no effect on troponin's ability to switch actin monomers on at high Ca2+ and inhibits their switching off at low Ca2+, the use of reagents that increase the Ca2+-sensitivity of the troponin complex may not be appropriate to restore muscle function in patients with this mutation. PMID- 29792864 TI - Delavatine A, an unusual isoquinoline alkaloid exerts anti-inflammation on LPS induced proinflammatory cytokines production by suppressing NF-kappaB activation in BV-2 microglia. AB - Delavatine A, an unusual isoquinoline alkaloid isolated from I. delavayi, was first studied for anti-inflammatory effect using lipopolysaccharide (LPS)-induced BV-2 microglia. In the present study, we found that delavatine A substantially suppressed the LPS-induced pro-inflammatory mediators, nitric oxide (NO), and tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1beta (IL 1beta) in BV-2 microglial cells. These effects resulted from the inhibition of their regulatory genes inducible NO synthase (iNOS), cycloxygenase-2 (COX-2) and TNF-a, IL-6, IL-1beta. In addition, we examined several pathways related to inflammation. The results revealed that delavatine A significantly decreased LPS induced the activation of nuclear factor-kappaB (NF-kappaB) by suppressing the p65 subunits, and the phosphorylation of IkappaBalpha, while not related to PI3K/Akt or MAPK pathways. PMID- 29792863 TI - Identification of immunodominant CD8 epitope in the stalk domain of influenza B viral hemagglutinin. AB - Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2Kd-restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus. Of three peptides selected through in silico analysis, the universally conserved peptide, YYSTAASSL (B/HA2-190), possessed the highest predicted binding affinity to MHC Class I and was most effective in inducing IL-2 and TNF-alpha in mouse splenocytes. Importantly, the peptide demonstrated best capability of stimulating peptide-specific ex-vivo cytotoxicity against target cells. Taken together, this finding would be of value for assessment of cell-mediated immune responses elicited by vaccines based on the highly conserved HA2 stalk domain. PMID- 29792865 TI - Aspirin restores ABT-737-mediated apoptosis in human renal carcinoma cells. AB - Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis. Such aspirin-induced changes of ABT-737 resistance was accompanied by a host of biochemical events like protein phosphatase 2A (PP2A) activation, AKT dephosphorylation, Mcl-1/FLICE inhibiting protein (FLIP)/XIAP downregulation, and Bax mitochondrial redistribution. The PP2A inhibitor, okadaic acid, was able to reverse the apirin-induced apoptotic changes. Apart from the aspirin treatment, Mcl-1 silencing also rendered cells vulnerable to ABT-737 induced apoptosis. Since PP2A, Akt, and Mcl-1 play critical roles in RCC malignancy and treatment resistance, our present study showed that aspirin, an alternative adjuvant agent, had recalled ABT-737 sensitivity in the RCC cells through processes involving the PP2A/Akt/Mcl-1 axis. PMID- 29792866 TI - Cardiac extracellular matrix hydrogel together with or without inducer cocktail improves human adipose tissue-derived stem cells differentiation into cardiomyocyte-like cells. AB - Studies have demonstrated that differentiation of stem cells into cardiomyocytes is a complex phenomenon that requires sufficient inducing factors at various time points. Cardiac extracellular matrix (cECM) could provide tissue specific microenvironment and act as an inductive template for efficient cell differentiation. The aim of this study was to investigate the effect of cECM on differentiation of human adipose tissue-derived stem cells (hADSCs) into cardiomyocytes using cECM hydrogel in combination with a cardiac inductive cocktail. hADSCs were cultured on ECM-coated plates with and without inductive cocktail for 3weeks. qRT-PCR and western blot analysis were used to evaluate the expression pattern of special cardiac genes and proteins. When hADSCs were cultured in the presence of cECM cardiac genes including GATA4, HAND1, HAND2, NKX2.5, Troponin I, betaMHC, Connexin43 were highly expressed in differentiated cells. Also Connexin43, cTnI and betaMHC proteins were expressed as well. We could show that cECM by itself could affect viability, proliferation and differentiation of hADSCs. However, combination of cECM with a cardiac inducing cocktail could improve the results. PMID- 29792868 TI - AH6809 decreases production of inflammatory mediators by PGE2 - EP2 - cAMP signaling pathway in an experimentally induced pure cerebral concussion in rats. AB - Increasing evidence suggests that PGE2 metabolic pathway is involved in pathological changes of the secondary brain injury after traumatic brain injury. However, the underlying mechanisms, in particular, the correlation between various key enzymes and the brain injury, has remained to be fully explored. More specifically, it remains to be ascertained whether AH6809 (an EP2 receptor antagonist) would interfere with the downstream of the PGE2, regulate the inflammatory mediators and improve neuronal damage in the hippocampus by PGE2 - EP2 - cAMP signaling pathway. The expression and pathological changes of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase-1 (mPGES-1), E-prostanoid receptor 2 (EP2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inducible nitricoxide synthase (iNOS) in the CA1 area of hippocampus were evaluated by immunohistochemistry, Western blot and RT-PCR after pure cerebral concussion (PCC) induced by a metal pendulum closed brain injury in rats followed by AH6809 treatment. The morphology and number of neurons in CA1 region were analyzed by cresyl violet staining. The concentration of prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) was assayed by ELISA. Many neurons in hippocampal CA1 area appeared to undergo necrosis and the number of neurons was concomitantly reduced after PCC injury. With the passage of time, the protein and mRNA expression of various key enzymes including COX-1, COX-2 and mPGES-1, EP2 receptor, and inflammatory mediators including TNF-alpha, IL-1beta and iNOS was increased; meanwhile, the concentration of PGE2 and cAMP was enhanced. After PCC injury given AH6809 intervention, injury of neurons in hippocampal CA1 area was attenuated. The protein and mRNA expression of COX-1, COX-2, mPGES-1, EP2, TNF-alpha, IL-1beta and iNOS was decreased, this was coupled with reduction of PGE2 and cAMP. The results suggest that PGE2 metabolic pathway is involved in secondary pathological changes of PCC. AH6809 improves the recovery of injured neurons in the hippocampal CA1 area and downregulates the inflammatory mediators by PGE2 - EP2 - cAMP signaling pathway. PMID- 29792867 TI - Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood. AB - Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D1 (SKF 82958) or D2 (quinpirole) receptor-selective agonist. In Experiment 2, pre-exposed rats were challenged during adulthood with AMPH and a D1 (SKF 83566) or D2 (eticlopride) receptor-selective antagonist. In Experiment 3, the activity of putative pyramidal cells in the prelimbic cortex was recorded as rats behaved in an open-field arena before and after challenge injections with AMPH and one of the antagonists. We found that compared to controls, adolescent pre-exposed rats were more sensitive to the stimulant effects of AMPH and the dopamine receptor agonists, as well as to the ability of the antagonists to reverse AMPH-induced stereotypy. Prelimbic neurons from AMPH pre-exposed rats were also more likely to respond to an AMPH challenge in adulthood, primarily by reducing their activity, and the antagonists reversed these effects. Our results suggest that exposure to AMPH during adolescence leads to enduring adaptations in the mesocorticolimbic dopamine system that likely mediate heightened response to the drug during adulthood. PMID- 29792869 TI - Preferential inputs from cholecystokinin-positive neurons to the somatic compartment of parvalbumin-expressing neurons in the mouse primary somatosensory cortex. AB - Parvalbumin-positive (PV+) neurons in the cerebral cortex, mostly corresponding to fast-spiking basket cells, have been implicated in higher-order brain functions and psychiatric disorders. We previously demonstrated that the somatic compartment of PV+ neurons received inhibitory inputs mainly from vasoactive intestinal polypeptide (VIP)+ neurons, whereas inhibitory inputs to the dendritic compartment were derived mostly from PV+ and somatostatin (SOM)+ neurons. However, a substantial number of the axosomatic inputs have remained unidentified. Here we show preferential innervation of the somatic compartment of PV+ neurons by cholecystokinin (CCK)+ neurons in the mouse primary somatosensory cortex. CCK+ neurons, a minor population of GABAergic neurons (3.2%), displayed no colocalization with PV or SOM immunoreactivity but partial overlap with VIP immunoreactivity (27.7%). Confocal laser scanning microscopy observation of CCK+ synaptic inputs to PV+ neurons revealed that CCK+ neurons preferred the somatic compartment to the dendritic compartment of PV+ neurons and provided approximately 33% of the axosomatic inhibitory inputs to PV+ neurons. Additionally, 20.9% and 12.1% of the axosomatic inputs were derived from CCK+/VIP+ and CCK+/VIP-negative (-) neurons, presumably double bouquet and large basket cells, respectively. Furthermore, the densities of the axosomatic inputs from CCK+ and/or VIP+ neurons to PV+ neurons were not significantly different among the cortical layers. The present findings suggest that, by preferentially innervating the cell bodies of PV+ neurons, both CCK+/VIP- basket and CCK+/VIP+ double bouquet cells might efficiently interfere with action potential generation of PV+ neurons, and that the two types of CCK+ neurons might have a large impact on cortical activity through PV+ neuron inhibition. PMID- 29792870 TI - Peripheral complement interactions with amyloid beta peptide in Alzheimer's disease: Polymorphisms, structure, and function of complement receptor 1. AB - INTRODUCTION: Genome-wide association studies consistently show that single nucleotide polymorphisms (SNPs) in the complement receptor 1 (CR1) gene modestly but significantly alter Alzheimer's disease (AD) risk. Follow-up research has assumed that CR1 is expressed in the human brain despite a paucity of evidence for its function there. Alternatively, erythrocytes contain >80% of the body's CR1, where, in primates, it is known to bind circulating pathogens. METHODS: Multidisciplinary methods were employed. RESULTS: Conventional Western blots and quantitative polymerase chain reaction failed to detect CR1 in the human brain. Brain immunohistochemistry revealed only vascular CR1. By contrast, erythrocyte CR1 immunoreactivity was readily observed and was significantly deficient in AD, as was CR1-mediated erythrocyte capture of circulating amyloid beta peptide. CR1 SNPs associated with decreased erythrocyte CR1 increased AD risk, whereas a CR1 SNP associated with increased erythrocyte CR1 decreased AD risk. DISCUSSION: SNP effects on erythrocyte CR1 likely underlie the association of CR1 polymorphisms with AD risk. PMID- 29792871 TI - Cerebral small vessel disease and the risk of dementia: A systematic review and meta-analysis of population-based evidence. AB - INTRODUCTION: Cerebral small vessel disease is increasingly linked to dementia. METHODS: We systematically searched Medline, Embase, and Cochrane databases for prospective population-based studies addressing associations of white matter hyperintensities, covert brain infarcts (i.e., clinically silent infarcts), and cerebral microbleeds with risk of all-dementia or Alzheimer's disease and performed meta-analyses. RESULTS: We identified 11 studies on white matter hyperintensities, covert brain infarcts, or cerebral microbleeds with risk of all dementia or Alzheimer's disease. Pooled analyses showed an association of white matter hyperintensity volume and a borderline association of covert brain infarcts with risk of all-dementia (hazard ratio: 1.39 [95% confidence interval: 1.00; 1.94], N = 3913, and 1.47 [95% confidence interval: 0.97; 2.22], N = 8296). Microbleeds were not statistically significantly associated with an increased risk of all-dementia (hazard ratio: 1.25 [95% confidence interval: 0.66; 2.38], N = 8739). DISCUSSION: White matter hyperintensities are associated with an increased risk of all-dementia and Alzheimer's disease in the general population. However, studies are warranted to further determine the role of markers of cerebral small vessel disease in dementia. PMID- 29792872 TI - Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease. AB - INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis. RESULTS: A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers. DISCUSSION: GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles. PMID- 29792875 TI - Modelling the skip-and-resurgence of Japanese encephalitis epidemics in Hong Kong. AB - Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne virus, persisting in pigs, Ardeid birds and Culex mosquitoes. It is endemic to China and Southeastern Asia. The case-fatality ratio (CFR) or the rate of permanent psychiatric sequelae is 30% among symptomatic patients. There were no reported local JEV human cases between 2006 and 2010 in Hong Kong, but it was followed by a resurgence of cases from 2011 to 2017. The mechanism behind this "skip-and resurgence" patterns is unclear. This work aims to reveal the mechanism behind the "skip-and-resurgence" patterns using mathematical modelling and likelihood based inference techniques. We found that pig-to-pig transmission increases the size of JEV epidemics but is unlikely to maintain the same level of transmission among pigs. The disappearance of JEV human cases in 2006-2010 could be explained by a sudden reduction of the population of farm pigs as a result of the implementation of the voluntary "pig-rearing licence surrendering" policy. The resurgence could be explained by of a new strain in 2011, which increased the transmissibility of the virus or the spill-over ratio from reservoir to host or both. PMID- 29792876 TI - Temperature-dependent sex determination, realized by hormonal dynamics with enzymatic reactions sensitive to ambient temperature. AB - Temperature-dependent sex determination (TSD) is adopted by many animal taxa, including reptiles and fishes. In some species, the eggs develop into females under a low hatching temperature, whereas they will develop into males under a high hatching temperature (called the FM-pattern). In other species, the eggs develop into males (or females) under a low (or high) hatching temperature (MF pattern). Still, in other species, the eggs develop into females, males, or females, respectively, when under a low, intermediate, or high hatching temperature (FMF-pattern). In this paper, we study a mechanism for realizing TSD. Specifically, we explore a hypothesis that the temperature dependence of enzymatic reaction rates causes a clear switching of sex hormone levels with gradual change of temperature. Herein, we analyze a simple hormonal-dynamics with temperature-sensitive rates of enzymatic reactions included in the sex determining gene-protein regulatory network. We first examined the cases in which the enzymatic reactions followed Arrhenius equation. The MF-pattern appeared when the rates of aromatase production and/or estradiol production depend more strongly on temperature than do the rates of their decay. By contrast, the FM pattern appeared when the temperature dependence is stronger for the decay rates of aromatase and/or estradiol than their production rates. However, the FMF pattern appeared only when some enzymatic reactions follow Berthelot-Hood equation, which exhibits a stronger temperature dependence under higher temperatures than Arrhenius equation. We discuss the possible mechanisms for TSD of FMF-pattern, including alternative splicing and post-translational modification. PMID- 29792873 TI - Effect of Alzheimer's disease risk and protective factors on cognitive trajectories in subjective memory complainers: An INSIGHT-preAD study. AB - INTRODUCTION: Cognitive change in people at risk of Alzheimer's disease (AD) such as subjective memory complainers is highly variable across individuals. METHODS: We used latent class growth modeling to identify distinct classes of nonlinear trajectories of cognitive change over 2 years follow-up from 265 subjective memory complainers individuals (age 70 years and older) of the INSIGHT-preAD cohort. We determined the effect of cortical amyloid load, hippocampus and basal forebrain volumes, and education on the cognitive trajectory classes. RESULTS: Latent class growth modeling identified distinct nonlinear cognitive trajectories. Education was associated with higher performing trajectories, whereas global amyloid load and basal forebrain atrophy were associated with lower performing trajectories. DISCUSSION: Distinct classes of cognitive trajectories were associated with risk and protective factors of AD. These associations support the notion that the identified cognitive trajectories reflect different risk for AD that may be useful for selecting high-risk individuals for intervention trials. PMID- 29792874 TI - PET staging of amyloidosis using striatum. AB - INTRODUCTION: Amyloid positron emission tomography (PET) data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. METHODS: We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. RESULTS: Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three category staging including only cortical amyloid. DISCUSSION: PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research. PMID- 29792877 TI - Coordinating Multi-Protein Mismatch Repair by Managing Diffusion Mechanics on the DNA. AB - DNA mismatch repair (MMR) corrects DNA base-pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic molecular coordination of sequential downstream pathways. The temporal and mechanistic order of molecular events is essential to insure interactions in MMR that occur over long distances on the DNA. Biophysical real-time studies of highly conserved components on mismatched DNA have shed light on the mechanics of MMR. Single-molecule imaging has visualized stochastically coordinated MMR interactions that are based on thermal fluctuation-driven motions. In this review, we describe the role of diffusivity and stochasticity in MMR beginning with mismatch recognition through strand-specific excision. We conclude with a perspective of the possible research directions that should solve the remaining questions in MMR. PMID- 29792878 TI - Deoxyelephantopin ameliorates lipopolysaccharides (LPS)-induced memory impairments in rats: Evidence for its anti-neuroinflammatory properties. AB - AIM: Neuroinflammation is a critical pathogenic mechanism of most neurodegenerative disorders especially, Alzheimer's disease (AD). Lipopolysaccharides (LPS) are known to induce neuroinflammation which is evident from significant upsurge of pro-inflammatory mediators in in vitro BV-2 microglial cells and in vivo animal models. In present study, we investigated anti-neuroinflammatory properties of deoxyelephantopin (DET) isolated from Elephantopus scaber in LPS-induced neuroinflammatory rat model. MATERIALS AND METHODS: In this study, DET (0.625. 1.25 and 2.5 mg/kg, i.p.) was administered in rats for 21 days and those animals were challenged with single injection of LPS (250 MUg/kg, i.p.) for 7 days. Cognitive and behavioral assessment was carried out for 7 days followed by molecular assessment on brain hippocampus. Statistical significance was analyzed with one-way analysis of variance followed by Dunnett's test to compare the treatment groups with the control group. KEY FINDINGS: DET ameliorated LPS-induced neuroinflammation by suppressing major pro-inflammatory mediators such as iNOS and COX-2. Furthermore, DET enhanced the anti-inflammatory cytokines and concomitantly suppressed the pro-inflammatory cytokines and chemokine production. DET treatment also reversed LPS-induced behavioral and memory deficits and attenuated LPS-induced elevation of the expression of AD markers. DET improved synaptic-functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95 and SYP. DET also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1, caspase-3 and cleaved caspase-3. SIGNIFICANCE: Overall, our studies suggest DET can prevent neuroinflammation-associated memory impairment and neurodegeneration and it could be developed as a therapeutic agent for the treatment of neuroinflammation mediated and neurodegenerative disorders, such as AD. PMID- 29792879 TI - Astragaloside suppresses apoptosis of the podocytes in rats with diabetic nephropathy via miR-378/TRAF5 signaling pathway. AB - AIMS: Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression. MATERIALS AND METHODS: The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively. Cell transfection was conducted for modulating endogenous expression of miR-378. Dual luciferase reporter assay was used to evaluate the interaction between miR 378 and TRAF5. The terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay was performed for apoptosis detection. KEY FINDINGS: AS-IV protected diabetic rats from developing into diabetic nephropathy. The expression of miR-378 was down-regulated in diabetic nephropathy rats, which was reversed by AS-IV. AS-IV enhanced the expression of miR-378 in podocytes treated with high glucose. MiR-378 negatively regulated TRAF5. AS-IV inhibited the expression of TRAF5 through miR-378. AS-IV suppressed apoptosis of podocytes via targeting miR 378. SIGNIFICANCE: AS-IV suppresses apoptosis of the podocytes through the miR 378/TRAF5 signaling pathway, and thereby repressing diabetic nephropathy development. PMID- 29792881 TI - The Temporal Association of Robotic Surgical Diffusion with Overtreatment of the Small Renal Mass. AB - PURPOSE: We evaluated contemporary practice patterns in the management of small renal masses. MATERIALS AND METHODS: We identified 52,804 patients in the NCDB (National Cancer Database) who were diagnosed with a small renal mass (4 cm or less) between 2010 and 2014. Utilization trends of active surveillance, ablation and robotic, laparoscopic and open surgical techniques were compared among all comers, elderly patients 75 years old or older and individuals with competing health risks, defined as a Charlson index of 2 or greater. Multivariable logistic regression models were used to assess factors associated with robotic renal surgery and active surveillance. RESULTS: Surgery remained the primary treatment modality across all years studied, performed in 75.0% and 74.2% of cases in 2010 and 2014, respectively. Although increases in active surveillance from 4.8% in 2010 to 6.0% in 2014 (p <0.001) and robotic renal surgery (22.1% in 2010 to 39.7% in 2014, p <0.001) were observed, the increase in the proportion of small renal masses treated with robotic partial and radical nephrectomy was greater than that of active surveillance (82.0% and 63.0%, respectively, vs 25.0%). Subgroup analyses in individuals 75 years old or older, or with a Charlson index of 2 or greater likewise revealed preferential increases in robotic surgery vs active surveillance. On multivariable analysis later year of diagnosis was associated with increased performance of robotic renal surgery compared to active surveillance (2014 vs 2010 OR 1.44, 95% CI 1.20-1.72, p <0.001) and nonrobotic procedural interventions (2014 vs 2010 OR 2.59, 95% CI 2.30-2.93, p <0.001). CONCLUSIONS: Robotic surgical extirpation has outpaced the adoption of active surveillance of small renal masses. This raises concern that the diffusion of robotic technology propagates overtreatment, particularly among elderly and comorbid individuals. PMID- 29792880 TI - Molecular alterations during larval development of Haemonchus contortus in vitro are under tight post-transcriptional control. AB - In this study, we explored the molecular alterations in the developmental switch from the L3 to the exsheathed L3 (xL3) and to the L4 stage of Haemonchus contortus in vitro using an integrated transcriptomic, proteomic and bioinformatic approach. Totals of 9,754 mRNAs, 88 microRNAs (miRNAs) and 1,591 proteins were identified, and 6,686 miRNA-mRNA pairs inferred in all larval stages studied. Approximately 16% of transcripts in the combined transcriptome (representing all three larval stages) were expressed as proteins, and there were positive correlations (r = 0.39-0.44) between mRNA transcription and protein expression in the three distinct developmental stages of the parasite. Of the predicted targets, 1,019 (27.0%) mRNA transcripts were expressed as proteins, and there was a negative correlation (r = -0.60 to -0.50) in the differential mRNA transcription and protein expression between developmental stages upon pairwise comparison. The changes in transcription (mRNA and miRNA) and protein expression from the free-living to the parasitic life cycle phase of H. contortus related to enrichments in biological pathways associated with metabolism (e.g., carbohydrate and lipid degradation, and amino acid metabolism), environmental information processing (e.g., signal transduction, signalling molecules and interactions) and/or genetic information processing (e.g., transcription and translation). Specifically, fatty acid degradation, steroid hormone biosynthesis and the Rap1 signalling pathway were suppressed, whereas transcription, translation and protein processing in the endoplasmic reticulum were upregulated during the transition from the free-living L3 to the parasitic xL3 and L4 stages of the nematode in vitro. Dominant post-transcriptional regulation was inferred to elicit these changes, and particular miRNAs (e.g., hco-miR-34 and hco-miR-252) appear to play roles in stress responses and/or environmental adaptations during developmental transitions of H. contortus. Taken together, these integrated results provide a comprehensive insight into the developmental biology of this important parasite at the molecular level in vitro. The approach applied here to H. contortus can be readily applied to other parasitic nematodes. PMID- 29792882 TI - Use of Automated Performance Metrics to Measure Surgeon Performance during Robotic Vesicourethral Anastomosis and Methodical Development of a Training Tutorial. AB - PURPOSE: We sought to develop and validate automated performance metrics to measure surgeon performance of vesicourethral anastomosis during robotic assisted radical prostatectomy. Furthermore, we sought to methodically develop a standardized training tutorial for robotic vesicourethral anastomosis. MATERIALS AND METHODS: We captured automated performance metrics for motion tracking and system events data, and synchronized surgical video during robotic assisted radical prostatectomy. Nonautomated performance metrics were manually annotated by video review. Automated and nonautomated performance metrics were compared between experts with 100 or more console cases and novices with fewer than 100 cases. Needle driving gestures were classified and compared. We then applied task deconstruction, cognitive task analysis and Delphi methodology to develop a standardized robotic vesicourethral anastomosis tutorial. RESULTS: We analyzed 70 vesicourethral anastomoses with a total of 1,745 stitches. For automated performance metrics experts outperformed novices in completion time (p <0.01), EndoWrist(r) articulation (p <0.03), instrument movement efficiency (p <0.02) and camera manipulation (p <0.01). For nonautomated performance metrics experts had more optimal needle to needle driver positioning, fewer needle driving attempts, a more optimal needle entry angle and less tissue trauma (each p <0.01). We identified 14 common robotic needle driving gestures. Random gestures were associated with lower efficiency (p <0.01), more attempts (p <0.04) and more trauma (p <0.01). The finalized tutorial contained 66 statements and figures. Consensus among 8 expert surgeons was achieved after 2 rounds, including among 58 (88%) after round 1 and 8 (12%) after round 2. CONCLUSIONS: Automated performance metrics can distinguish surgeon expertise during vesicourethral anastomosis. The expert vesicourethral anastomosis technique was associated with more efficient movement and less tissue trauma. Standardizing robotic vesicourethral anastomosis and using a methodically developed tutorial may help improve robotic surgical training. PMID- 29792884 TI - Pharmacological inhibition of DNA methylation attenuates pressure overload induced cardiac hypertrophy in rats. AB - BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes. METHODS AND RESULTS: Young male Wistar rats were subjected to PO by transverse aortic constriction (TAC) or to sham surgery. Rats from both groups received solvent or 12.5 mg/kg body weight of the non-nucleosidic DNMT inhibitor RG108, initiated on the day of the intervention. After 4 weeks, we analysed cardiac function by MRI, fibrosis with Sirius Red staining, gene expression by RNA sequencing and qPCR, and DNA methylation by reduced representation bisulphite sequencing (RRBS). RG108 attenuated the ~70% increase in heart weight/body weight ratio of TAC over sham to 47% over sham, partially rescued reduced contractility, diminished the fibrotic response and the downregulation of a set of genes including Atp2a2 (SERCA2a) and Adrb1 (beta1-adrenoceptor). RG108 was associated with significantly lower global DNA methylation in cardiomyocytes by ~2%. The differentially methylated pathways were "cardiac hypertrophy", "cell death" and "xenobiotic metabolism signalling". Among these, "cardiac hypertrophy" was associated with significant methylation differences in the group comparison sham vs. TAC, but not significant between sham+RG108 and TAC+RG108 treatment, suggesting that RG108 partially prevented differential methylation. However, when comparing TAC and TAC+RG108, the pathway cardiac hypertrophy was not significantly differentially methylated. CONCLUSIONS: DNMT inhibitor treatment is associated with attenuation of cardiac hypertrophy and moderate changes in cardiomyocyte DNA methylation. The potential mechanistic link between these two effects and the role of non-myocytes need further clarification. PMID- 29792885 TI - Effects of vasopressin on neural processing of infant crying in expectant fathers. AB - In a randomized, double blind, placebo-controlled, within-subject magnetic resonance imaging study, we examined the effect of 20 IU intranasal vasopressin on the neural processing of infant crying in 25 fathers-to-be. We explored whether familial background modulates vasopressin effects, and whether vasopressin differentially affects cry processing coupled with neutral or emotional contextual information. Participants listened to cries accompanied by neutral ('this is an infant') or emotional ('this infant is sick/bored') contextual information, and neutral control sounds ('this is a saw'). Additionally, participants reported on their childhood experiences of parental love-withdrawal and abuse. Infant crying (vs control sounds) was associated with increased activation in the bilateral auditory cortex and posterior medial cortex. No effects of vasopressin were found in this 'cry network'. Exploratory whole-brain analyses suggested that effects of vasopressin in the anterior cingulate cortex, paracingulate gyrus and supplemental motor area were stronger in fathers who experienced lower (vs higher) levels of love-withdrawal. No interaction was observed for abuse. Vasopressin increased activation in response to cries accompanied by emotional vs neutral contextual information in several brain regions, e.g. the cerebellum, brainstem (midbrain), posterior medial cortex, hippocampus, putamen, and insula. Our results suggest that the experience of love-withdrawal may modulate the vasopressin system, influencing effects of vasopressin administration on cry processing. Results further suggest a role for vasopressin in the processing of cry sounds with emotional contextual information. PMID- 29792883 TI - Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases. AB - BACKGROUND & AIMS: Biomarkers are needed for early detection of Crohn's disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex posttranslational modification of proteins that affects their structure and activity. We compared plasma N-glycosylation profiles between patients with CD or UC and healthy individuals (controls). METHODS: We analyzed the total plasma N-glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique. Plasma samples were acquired from 2 hospitals in Italy (discovery cohort, 1989 patients with inflammatory bowel disease [IBD] and 570 controls) and 1 medical center in the United States (validation cohort, 646 cases of IBD and 426 controls). Sixty-three glycoforms met our criteria for relative quantification and were extracted from the raw data with the software MassyTools. Common features shared by the glycan compositions were combined in 78 derived traits, including the number of antennae of complex-type glycans and levels of fucosylation, bisection, galactosylation, and sialylation. Associations of plasma N-glycomes with age, sex, CD, UC, and IBD-related parameters such as disease location, surgery and medication, level of C-reactive protein, and sedimentation rate were tested by linear and logistic regression. RESULTS: Plasma samples from patients with IBD had a higher abundance of large-size glycans compared with controls, a decreased relative abundance of hybrid and high-mannose structures, lower fucosylation, lower galactosylation, and higher sialylation (alpha2,3- and alpha2,6-linked). We could discriminate plasma from patients with CD from that of patients with UC based on higher bisection, lower galactosylation, and higher sialylation (alpha2,3-linked). Glycosylation patterns were associated with disease location and progression, the need for a more potent medication, and surgery. These results were replicated in a large independent cohort. CONCLUSIONS: We performed high-throughput analysis to compare total plasma N glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients' responses to treatment. PMID- 29792886 TI - t-GRASP, a targeted GRASP for assessing neuronal connectivity. AB - BACKGROUND: Understanding how behaviors are generated by neural circuits requires knowledge of the synaptic connections between the composite neurons. Methods for mapping synaptic connections, such as electron microscopy and paired recordings, are labor intensive and alternative methods are thus desirable. NEW METHOD: Development of a targeted GFP Reconstitution Across Synaptic Partners(GRASP) method, t-GRASP, for assessing neural connectivity is described. RESULTS: Numerous different pre-synaptic and post-synaptic/dendritic proteins were tested for enhancing the specificity of GRASP signal to synaptic regions. Pairing of both targeted pre- and post-t-GRASP constructs resulted in strong preferential GRASP signal in synaptic regions in Drosophila larval sensory neurons, larval neuromuscular junctions, and adult photoreceptor neurons with minimal false positive signal. COMPARISON WITH EXISTING METHODS: Activity-independent t-GRASP exhibits an enhancement of GRASP signal specificity for synaptic contact sites as compared to existing Drosophila GRASP methods. Fly strains were developed for expression of both pre- and post-t-GRASP with each of the three Drosophila binary transcription systems, thus enabling GRASP assays to be performed between any two driver pairs of any transcription system in either direction, an option not available for existing Drosophila GRASP methods. CONCLUSIONS: t-GRASP is a novel targeted GRASP method for assessing synaptic connectivity between Drosophila neurons. Its flexibility of use with all three Drosophila binary transcription systems significantly expands the potential use of GRASP in Drosophila. PMID- 29792887 TI - Auditory priming improves neural synchronization in auditory-motor entrainment. AB - Neurophysiological research has shown that auditory and motor systems interact during movement to rhythmic auditory stimuli through a process called entrainment. This study explores the neural oscillations underlying auditory motor entrainment using electroencephalography. Forty young adults were randomly assigned to one of two control conditions, an auditory-only condition or a motor only condition, prior to a rhythmic auditory-motor synchronization condition (referred to as combined condition). Participants assigned to the auditory-only condition auditory-first group) listened to 400 trials of auditory stimuli presented every 800 ms, while those in the motor-only condition (motor-first group) were asked to tap rhythmically every 800 ms without any external stimuli. Following their control condition, all participants completed an auditory-motor combined condition that required tapping along with auditory stimuli every 800 ms. As expected, the neural processes for the combined condition for each group were different compared to their respective control condition. Time-frequency analysis of total power at an electrode site on the left central scalp (C3) indicated that the neural oscillations elicited by auditory stimuli, especially in the beta and gamma range, drove the auditory-motor entrainment. For the combined condition, the auditory-first group had significantly lower evoked power for a region of interest representing sensorimotor processing (4-20 Hz) and less total power in a region associated with anticipation and predictive timing (13-16 Hz) than the motor-first group. Thus, the auditory-only condition served as a priming facilitator of the neural processes in the combined condition, more so than the motor-only condition. Results suggest that even brief periods of rhythmic training of the auditory system leads to neural efficiency facilitating the motor system during the process of entrainment. These findings have implications for interventions using rhythmic auditory stimulation. PMID- 29792888 TI - Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence. AB - So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor gamma (PPAR-gamma), respectively, in activated HSCs. However, efficacy on AT1R and PPAR-gamma necessitates high drug permeability which is lacking in valsartan. In the current study, liposomes were used as nanocarriers for valsartan to improve its permeability and hence efficacy. They were coupled to VA and characterized for HSCs-targeting. Tracing of orally-administered fluorescently labeled VA-coupled liposomes in normal rats and their fluorescence intensity quantification in different organs convincingly demonstrated their intestinal entrapment. On the other hands, their administration to rats with induced fibrosis revealed preferential hepatic, and less intestinal, accumulation which lasted up to six days. This indicated their uptake by intestinal stellate cells that acted as a depot for their release over time. Confocal microscopical examination of immunofluorescently-stained HSCs in liver sections, with considerable formula accumulation, confirmed HSCs-targeting and nuclear uptake. Consequently, VA-coupled valsartan-loaded liposomes (VLC)-therapy resulted in profound re-expression of hepatic Mas-receptor and PPAR-gamma, potent reduction of fibrogenic mediators' level and nearly normal liver function tests. Therefore, VLC epitomizes a promising antifibrotic therapy with exceptional extended action and additional PPAR-gamma agonistic activity. PMID- 29792890 TI - The visual cortex and visual cognition in Huntington's disease: An overview of current literature. AB - The processing of visual stimuli from retina to higher cortical areas has been extensively studied in the human brain. In Huntington's disease (HD), an inherited neurodegenerative disorder, it is suggested that visual processing deficits are present in addition to more characteristic signs such as motor disturbances, cognitive dysfunction, and behavioral changes. Visual deficits are clinically important because they influence overall cognitive performance and have implications for daily functioning. The aim of this review is to summarize current literature on clinical visual deficits, visual cognitive impairment, and underlying visual cortical changes in HD patients. A literature search was conducted using the electronic database of PubMed/Medline. This review shows that changes of the visual system in patients with HD were not the primary focus of currently published studies. Still, early atrophy and alterations of the posterior cerebral cortex was frequently observed, primarily in the associative visual cortical areas such as the lingual and fusiform gyri, and lateral occipital cortex. Changes were even present in the premanifest phase, before clinical onset of motor symptoms, suggesting a primary region for cortical degeneration in HD. Although impairments in visuospatial processing and visual perception were reported in early disease stages, heterogeneous cognitive batteries were used, making a direct comparison between studies difficult. The use of a standardized battery of visual cognitive tasks might therefore provide more detailed information regarding the extent of impairments in specific visual domains. Further research could provide more insight into clinical, functional, and pathophysiological changes of the visual pathway in HD. PMID- 29792889 TI - ROS-triggered degradable iron-chelating nanogels: Safely improving iron elimination in vivo. AB - Iron-mediated generation of highly toxic Reactive Oxygen Species (ROS) plays a major role in the process leading to iron overload-related diseases. The long term subcutaneous administration of Deferoxamine (DFO) is currently clinically approved to improve patient symptoms and survival. However, non-specific toxicity and short circulation times of the drug in humans often leads to poor patient compliance. Herein, thioketal-based ROS-responsive polymeric nanogels containing DFO moieties (rNG-DFO) were designed to chelate iron and to degrade under oxidative stimuli into fragments <10 nm to enhance excretion of iron-bound chelates. Serum ferritin levels and iron concentrations in major organs of IO mice decreased following treatment with rNG-DFO, and fecal elimination of iron bound chelates increased compared to free DFO. Furthermore, rNG-DFO decreased iron mediated oxidative stress levels in vitro and reduced iron-mediated inflammation in the liver of IO mice. The study confirms that ROS-responsive nanogels may serve as a promising alternative to DFO for safer and more efficient iron chelation therapy. PMID- 29792892 TI - Beef quality labels: A combination of sensory acceptance test, stated willingness to pay, and choice-based conjoint analysis. AB - Consumer perspectives of beef quality are complex, leading to a market that is increasingly differentiating. Thus, ongoing monitoring and assessment of changes in consumer perspectives is essential to identify changing market conditions. Often only credence and search characteristics are evaluated in consumer studies; therefore the object of the present study is to examine consumer preferences and perceptions towards beef steaks, also including experience characteristics, using a mixed methods approach. For this reason, 55 consumers participated in an experiment in Germany, including a sensory acceptance test, stated willingness to pay, and choice-based conjoint analysis (CBCA). Different quality characteristics were included, but a focus on the quality labels of 'dry aged beef', 'Block House beef', and 'Angus beef' was predominant throughout the experiment with the results showing that quality labels significantly increased overall liking as well as the stated willingness to pay. Quality labels were also the one of the most important characteristics in the conjoint analysis, after origin and price. The results of all applied methods are comparable for the characteristic quality label. The combination of sensory acceptance test and CBCA were additionally able to evaluate all three kinds of beef quality characteristics, which could not be evaluated together only using a single method. This suggests that a mixture of methods should be used to gain better knowledge on the true behavior of beef consumers. Experience and credence characteristics, including beef quality labels, present opportunities for future research as well as the potential for determining product and market differentiation. PMID- 29792891 TI - PCL/EUG scaffolds with tunable stiffness can regulate macrophage secretion behavior. AB - Osteoarthritis (OA) is a prevalent joint disorder worldwide. Recent studies suggested that macrophages play an important role in the progression of OA. However, the detailed pathology related to macrophages is still ambiguous, especially those related to mechanotransduction. In this study, PCL/EUG composite scaffolds were first fabricated by electrospinning. The stiffness of as fabricated scaffolds was controlled by adjusting the PCL-versus-EUG ratio. The mechanical properties, structural characterics and chemical composition of the scaffolds were investigated using various materials characterization techniques. The results showed that the stiffness of the scaffolds was in the same range as the cartilage tissues with OA. Confocal microscope and RT-PCR were performed to investigate the macrophages cultured on the scaffolds. Significant morphological change of cells was observed. The expression of inflammatory and fibrosis-related cytokines increases as the scaffold stiffness decreases, similar to the trend observed in OA progression. PMID- 29792893 TI - TOX expression decreases with progression of colorectal cancers and is associated with CD4 T-cell density and Fusobacterium nucleatum infection. AB - Fusobacterium nucleatum in the tumor microenvironment plays an important role in the development of colorectal cancer. The underlying mechanism of action, however, remains to be elucidated. We evaluated the relation of F nucleatum amount to thymocyte selection-associated high-mobility group box (TOX) protein expression and CD4+ T-cell density in 138 human colorectal tissues. TOX expression and CD4+ T-cell density in Fnucleatum-negative tissues were significantly higher compared to those in Fnucleatum-positive tissues (P < .001 and P = .002, respectively). We found a negative correlation between F nucleatum abundance and TOX expression (P < .001) and CD4+ T-cell density (P < .001). TOX expression in normal mucosa, hyperplastic polyps, and adenomas was significantly higher than in sessile serrated adenomas and different stages of carcinomas (P < .05). Moreover, CD4+ T-cell density in high-TOX expression tissues was significantly higher than in low-TOX expression tissues (P = .003). A positive correlation was found between TOX expression and CD4+ T-cell density in colorectal tissues (Spearman correlation coefficient: 0.362, 95% confidence interval: 0.051-0.641, P = .022). Our findings suggest that F nucleatum may suppress antitumor immune responses by decreasing CD4+ T-cell density and TOX expression in the progression of colorectal cancer. PMID- 29792894 TI - Medical students reflect on the future of Pre-Exposure Prophylaxis use among adolescents and young adults. PMID- 29792895 TI - Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications. AB - A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had taken a five-day course of amoxicillin clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 * 109/L (normal 3.6-9.3), haemoglobin 11.8 g/dl (normal 11-15), platelet count 356 * 109/L (normal 170-420), sodium 138 mmol/L (normal 134-144), potassium 3.5 mmol/L (normal 3.5-5.0), creatinine 32 umol/L (normal 40-75), albumin 30 g/L (normal 35-48), alanine aminotransferase 707 IU/L (normal 15-54), alkaline phosphatase 151 IU/L (normal 30-130), bilirubin 384 umol/L (normal 7-31) and prothrombin time 27.2 s (normal 11.7-14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells. Her clinical condition deteriorated in the following days with prothrombin time and bilirubin rising to 56.6 s and 470 umol/L, respectively. At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. Human leucocyte antigen (HLA) typing was performed as a part of preparatory investigations and showed the patient carried the HLA haplotype HLA-DRB1*15:02-DQB1*06:01. Following orthotopic transplantation of a deceased donor graft her explant histology revealed severe ongoing hepatitis with multi-acinar necrosis (Fig. 1A and B). This case raised a number of important questions about the diagnosis of drug-induced liver injury and tools available for clinicians to make the best decisions for patient care: In this Grand Rounds article, we will explore these questions, describing the pathophysiology, diagnostic and prognostic biomarkers, and clinical management of drug-induced liver injury. We will also discuss ongoing areas of uncertainty. PMID- 29792896 TI - Exploring new treatment paradigms for alcoholic hepatitis by extrapolating from NASH and cholestasis. PMID- 29792897 TI - Mathematical modeling and numerical simulation of the mitotic spindle orientation system. AB - The mitotic spindle orientation and position is crucial for the fidelity of chromosome segregation during asymmetric cell division to generate daughter cells with different sizes or fates. This mechanism is best understood in the budding yeast Saccharomyces cerevisiae, named the spindle position checkpoint (SPOC). The SPOC inhibits cells from exiting mitosis until the mitotic spindle is properly oriented along the mother-daughter polarity axis. Despite many experimental studies, the mechanisms underlying SPOC regulation remains elusive and unexplored theoretically. Here, a minimal mathematical is developed to describe SPOC activation and silencing having autocatalytic feedback-loop. Numerical simulations of the nonlinear ordinary differential equations (ODEs) model accurately reproduce the phenotype of SPOC mechanism. Bifurcation analysis of the nonlinear ODEs reveals the orientation dependency on spindle pole bodies, and how this dependence is altered by parameter values. Partial differential equation (PDEs) model as well as linear stability analysis indicate that diffusion play no major role using experimental high diffusion values. These results provide for systems understanding on the molecular organization of spindle orientation system via mathematical modeling. The presented mathematical model is easy to understand and, within the above mentioned context, can be used as a base for further development of quantitative models in asymmetric cell-division. PMID- 29792898 TI - Energy drink exposures reported to Texas poison centers: Analysis of adverse incidents in relation to total sales, 2010-2014. AB - The ill-defined term "energy drink" includes a disparate group of products (beverages, shots, concentrates, and workout powders) having large differences in caffeine content and concentration and intended use. Hence, inaccurate conclusions may be drawn when describing adverse events associated with "energy drinks". The FDA is considering new regulation of these products but product specificity is needed to evaluate safety. To help address this, we queried Texas Poison Center Network data for single substance exposures to "energy drinks" from 2010 to 2014, then analyzed adverse events by product type. We specifically compared energy beverage exposures with sales data for the same time period to evaluate the safety profile of this category of energy drinks. Among 855 documented "energy drink" exposures, poison center-determined outcome severity revealed 291 with no/minimal effects, 417 judged nontoxic or minor/not followed, 64 moderate and 4 major effects, and no deaths. Serious complications included 2 seizures and 1 episode of ventricular tachycardia. Outcome severity by category for beverages: 11 moderate/1 major effects (none in children <17 years); shots: 19 moderate/2 major; non-liquids: 16 moderate/1 major; concentrates: 7 moderate; unknown: 10 moderate. Call incidence to poison centers for beverage type exposures was 0.58 (for moderate effects) and 0.053 (for major) per hundred million units sold. Small volume and concentrated products were associated with a greater number of adverse effects than beverage versions of "energy drinks". PMID- 29792899 TI - Protective effect of exendin-4 treatment on erectile dysfunction induced by chronic methylglyoxal administration in rats. AB - OBJECTIVE: The aim of this study was to investigate the effect of chronic exendin 4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats. METHODS: Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 MUg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 MUg/kg twice daily subcutaneously for 12 weeks concomitant with MGO). Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxations were evaluated by acetylcholine (ACh) and electrical field stimulation (EFS), respectively. Apoptosis was determined by TUNEL. Endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), NADPH oxidase subunit gp91phox (NOX2), and Rho kinase (ROCK2) expressions in CC were investigated by immunohistochemistry. Levels of the malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were also measured. RESULTS: In MGO administered rats, both endothelium-dependent and neurogenic CC relaxations were significantly impaired as compared to controls. Apoptotic cell death and levels of MDA and AOPP increased significantly in MGO administered rats. eNOS and p-eNOS expressions decreased significantly in MGO group, while gp91phox expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of proteins in MGO groups were significantly improved by exendin-4 treatment. TUNEL-positive cells, and levels of MDA and AOPP in MGO group rats were also significantly reduced by exendin-4. CONCLUSION: Exendin-4 treatment improves NO-mediated CC relaxations in MGO administered rats probably by inhibiting NADPH oxidase. PMID- 29792900 TI - The sulfoconjugation of androstenone and dehydroepiandrosterone by human and porcine sulfotransferase enzymes. AB - Porcine sulfotransferase 2A1 (pSULT2A1) is a key enzyme involved in the testicular and hepatic sulfoconjugation of steroids such as dehydroepiandrosterone (DHEA) and potentially androstenone. This latter steroid is a major cause of boar taint, which is an unpleasant off-odour and off-flavour in pork from male pigs. Sulfotransferase 2B1 (pSULT2B1) may also be important, although no direct evidence exists for its involvement in sulfoconjugation of steroids. The purpose of this study was to investigate the sulfoconjugation activity of human and porcine sulfotransferases towards DHEA and androstenone. pcDNA 3.1 vectors expressing porcine (p) SULT2A1, pSULT2B1, human (h) SULT2A1, hSULT2B1a, and hSULT2B1b enzymes were transfected into human embryonic kidney cells. Transfected cells were then incubated with either androstenone or dehydroepiandrosterone (DHEA) in both time-course and enzyme kinetics studies. The production of sulfonates of androstenone metabolites and DHEA sulfonate increased over time for all enzymes with the exception of pSULT2B1. Enzyme kinetics analysis showed that androstenone and DHEA were poor substrates for the human orthologs, hSULT2B1a and hSULT2B1b. Human and porcine SULT2A1 showed substantially different substrate affinities for androstenone (Km 5.8 +/- 0.6 uM and 74.1 +/- 15.9 uM, respectively) and DHEA (Km 9.4 +/- 2.5 uM and 3.3 +/- 1.9 uM, respectively). However, these enzymes did show relatively similar sulfonation efficiencies for DHEA (Vmax/Km 50.5 and 72.9 for hSULT2A1 and pSULT2A1, respectively). These results highlight the species differences in sulfonation activity and provide direct evidence, for the first time, suggesting that pSULT2B1 is not involved in sulfonation of either androstenone metabolites or DHEA. PMID- 29792902 TI - Session 4 discussion: The built environment. AB - The following is a transcript from "The Built Environment" session during the Ingestive Behavior Research Conference at Purdue University. PMID- 29792901 TI - Identification and functional characterization, including cytokine production modulation, of the novel chicken Interleukin-11. AB - Interleukin (IL)-11 plays an important role in the immune system. However, IL-11 has not yet been characterized in avian species, including chickens. This study is the first to clone and functionally characterize chicken IL-11 (chIL-11). Multiple alignments and phylogenetic tree comparisons of chIL-11 with IL-11 proteins from other species revealed high levels of conservation and a close relationship between chicken and Japanese quail IL-11. Our results demonstrate that chIL-11 was a functional ligand of IL-11RA and IL-6ST in chicken HD11 and OU2 cell lines, as well as activated and regulated JAK-STAT, NF-kappaB, PI3K/AKT, and MAPK signaling pathways in chicken cell lines. In addition, chIL-11 inhibited nitric oxide production, affected proliferation of both tested cell lines, inhibited Type 1 and 17 T helper (Th) cytokine and IL-26, IL-12, and IL-17A induced interferon-gamma production, and enhanced Th2 cytokine (IL-4 and IL-10) production. Taken together, functional analysis of chIL-11 revealed it bound to IL-11RA and IL-6ST and activated the JAK-STAT, NF-kappaB, and MAPK signaling pathways, which resulted in modulation of Th1/Th17 and Th2 cytokine production in chicken HD11 and OU2 cell lines. Overall, this indicates chIL-11 has a role in both the innate and adaptive immune system. PMID- 29792903 TI - Endogenous pararetrovirus sequences are widely present in Citrinae genomes. AB - Endogenous pararetroviruses (EPRVs) are characterized in several plant genomes and their biological effects have been reported. In this study, hundreds of EPRV segments were identified in six Citrinae genomes. A total of 1034 EPRV segments were identified in the genomes of sweet orange, 2036 in pummelo, 598 in clementine mandarin, 752 in Ichang papeda, 2060 in citron and 245 in atalantia. Genomic analysis indicated that EPRV segments tend to cluster as hot spots in the genomes, particularly on chromosome 2 and 5. Large numbers of simple repeats and transposable elements were identified in the 2-kb flanking regions of the EPRV segments. Comparative genomic analysis and PCR experiments showed that there are highly conserved EPRV segments and species-specific EPRV segments between the Citrinae genomes. Phylogenetic analysis suggested that the integration events of EPRVs could initiate in a common progenitor of Citrinae species and repeatedly occur during the Citrinae divergence. PMID- 29792904 TI - Monoclonal Antibody DL11C8 Identifies ADAM23 as a Component of Lipid Raft Microdomains. AB - A disintegrin and metalloprotease protein 23 (ADAM23) is a transmembrane type I glycoprotein involved with the development and maintenance of the nervous system, including neurite outgrowth, neuronal adhesion and differentiation and regulation of synaptic transmission. In addition, ADAM23 seems to participate in immune response and tumor establishment through interaction with different members of integrin receptors. Here, we describe a novel monoclonal antibody (DL11C8) that specifically recognizes the cysteine-rich domain of both pre-protein (100 kDa) and mature (70 kDa) forms of ADAM23 from different species, including human, rodents and avian orthologs. Using this antibody, we detected both forms of ADAM23 on the cell surface of three neuronal cell lineages (Neuro-2a, SH-SY5Y and CHLA-20), with a higher relative content of ADAM23100 kDa. Furthermore, we demonstrate for the first time that a catalytically inactive member of the ADAM family is present in the membrane signaling platforms, namely lipid rafts. Indeed, the mature ADAM2370 kDa partitions between raft and non-raft membrane domains, while the pro-protein ADAM23100 kDa is mainly expressed in non-raft domains. These membranous distributions were observed in both different brain regions homogenates and primary cultured neurons lysates from mouse cortex and cerebellum. Taken together, these findings point out ADAM23 as a lipid raft molecular component. PMID- 29792905 TI - Together Means More Happiness: Relationship Status Moderates the Association between Brain Structure and Life Satisfaction. AB - Life satisfaction reflects an individual's general evaluation of their overall quality of life. It has been hypothesized that relationship status (i.e. state of intimate relationship such as marriage, unmarried cohabiting, dating with others, single or divorce) may influence individual life satisfaction. However, there is little accessible empirical evidence that allows us to explore this proposition. Using a large sample of young adults (n = 1031) from the Human Connectome Project (HCP), we showed that compared to other relationship statuses (e.g., individuals who were single or divorced, individuals who dated others, and etcetera), marriage/cohabitation subjects not only revealed a higher life satisfaction plus higher emotional and instrumental support, but also reduced perceived stress, which contributed to higher life satisfaction. Using general linear model with cortical thickness as the dependent variable, life satisfaction was negatively associated with the left superior frontal gyrus (SFG) and bilateral middle frontal gyrus (MFG). Interestingly, both right MFG and left SFG could interact with relationship status to predict self-reported life satisfaction, in addition to being associated with a much lower life satisfaction in non-married/cohabiting individuals. These effects were independent of emotional, instrumental support, and socioeconomic status. Besides, statistical significance of the moderation effect pertaining to relationship status was lost once perceived stress was included as a covariate into the moderation model. Our findings provided empirical evidence for the potentially positive role of relationship status in life satisfaction, and also showed that remission of stress may be a critical factor. PMID- 29792906 TI - Four novel antibacterial sesquiterpene-alpha-amino acid quaternary ammonium hybrids from the mycelium of mushroom Stereum hirsutum. AB - The mushroom Stereum hirsutum is parasitized by Tremella aurantia to form a heterogeneous basidiocarp Jin'er, which has been used as food and folk medicine in Chinese society. In present work, the S. hirsutum was fermented in YMG broth, and four novel mixed terpenes, stereumamides A-D (1-4), which are sesquiterpenes combined with alpha-amino acids to form quaternary ammonium hybrids, were isolated from the Stereum hirsutum FP-91666 and their structures were elucidated by spectroscopic data analysis. Stereumamides A and D showed antibacterial activity against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium, with the minimum inhibitory concentration (MIC) values of 12.5-25.0 MUg/mL. The stereumamides A-D should be apparently the first example of naturally occurring a quaternary ammonium compound (QAC) conjugated by sesquiterpene with an alpha-amino acid. QAC is a common antibacterial agent in food industry, which is found in the mycelium of Stereum hirsutum would suggest that the complex basidiocarp is a functional food and veritable folk medicine. PMID- 29792907 TI - Electrocortical reactivity to negative and positive facial expressions in individuals with a family history of major depression. AB - Facial expressions signaling threat and mood-congruent loss have been used to probe abnormal neural reactivity in major depressive disorder (MDD) and may be implicated in genetic vulnerability to MDD. This study investigated electro cortical reactivity to facial expressions in 101 unaffected, adult first-degree relatives of probands with MDD and non-relative controls (n = 101). We investigated event-related potentials (ERPs) to five facial expressions of basic emotion: fear, anger, disgust, sadness and happiness under both subliminal (masked) and conscious (unmasked) presentation conditions, and the source localization of group differences. In the conscious condition, controls showed a distinctly positive-going shift in responsive to negative versus happy faces, reflected in a greater positivity for the VPP frontally and the P300 parietally, and less negativity for the N200. By contrast, relatives showed less differentiation of emotions, reflected in less VPP and P300 positivity, particularly for anger and disgust, which produced an enhanced N200 for sadness. These group differences were consistently source localized to the anterior cingulate cortex. The findings contribute new evidence for neural disruptions underlying the differentiation of salient emotions in familial risk for depression. These disruptions occur to the appraisal (~200 ms post-stimulus) through to the context evaluation (~300 ms+ post-stimulus) phases of emotion processing, consistent with theories that risk for depression involves biased or attenuated processing of emotion. PMID- 29792908 TI - Acute effects of caffeine on threat-selective attention: moderation by anxiety and EEG theta/beta ratio. AB - BACKGROUND: Spontaneous EEG theta/beta ratio (TBR) probably marks prefrontal cortical (PFC) executive control, and its regulation of attentional threat-bias. Caffeine at moderate doses may strengthen executive control through increased PFC catecholamine action, dependent on basal PFC function. GOAL: To test if caffeine affects threat-bias, moderated by baseline frontal TBR and trait-anxiety. METHODS: A pictorial emotional Stroop task was used to assess threat-bias in forty female participants in a cross-over, double-blind study after placebo and 200 mg caffeine. RESULTS: At baseline and after placebo, comparable relations were observed for negative pictures: high TBR was related to low threat-bias in low trait-anxious people. Caffeine had opposite effects on threat-bias in low trait-anxious people with low and high TBR. CONCLUSIONS: This further supports TBR as a marker of executive control and highlights the importance of taking baseline executive function into consideration when studying effects of caffeine on executive functions. PMID- 29792909 TI - Dermatofibrosarcoma protuberans: A retrospective study of clinicopathologic features and related Akt/mTOR, STAT3, ERK, cyclin D1, and PD-L1 expression. AB - BACKGROUND: Little is known regarding oncoproteins other than platelet-derived growth factor subunit B in dermatofibrosarcoma protuberans (DFSP). Moreover, the risk factors for worse prognosis are controversial. OBJECTIVE: We sought to determine the clinicopathologic features and key factors for adverse outcome in DFSP, including the implication of expression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), extracellular signal regulated kinase (ERK), cyclin D1, and programmed death ligand 1 (PD-L1). METHODS: Clinicopathologic and immunohistochemical analyses were performed for 44 DFSPs having wide local excision and 92 dermatofibromas as controls. RESULTS: Compared with the 35 nonrecurrent DFSPs, the 9 recurrent DFSPs exhibited larger tumor size, deeper invasion beyond the subcutis, and more diverse histologic subtype. The fibrosarcomatous subtype revealed frequent mitotic figures and a high cyclin D1-positive index. The 2 metastatic DFSPs (1 each of the fibrosarcomatous and myxoid subtypes) demonstrated 4 and 11 instances of local recurrence, respectively, as well as larger tumor size, deeper invasion beyond the subcutis, and high expression of cyclin D1. Expression of Akt/mTOR, STAT3, ERK, and PD-L1 ranged from none or low in the primary skin lesions to high in the corresponding metastatic sites. Akt/mTOR and ERK were expressed more frequently in DFSP than in dermatofibroma. LIMITATIONS: Lack of information on patients before hospital evaluation. CONCLUSION: Complex factors beyond fibrosarcomatous subtype may portend local recurrence or metastasis. Akt/mTOR, STAT3, ERK, and PD-L1 may be associated with development and/or progression of DFSP. PMID- 29792910 TI - Perception of children with visible untreated and treated caries. AB - OBJECTIVES: This study aimed to analyse if children with untreated or treated caries (restorations/missing teeth) are perceived differently compared to children with healthy teeth and to explore possible differences in the perception by laypersons and dental experts. METHODS: Eye movements of female experts (n = 20) and laypersons (n = 18) were recorded by eye-tracking while paired images (neutral expression/teeth not visible; emotional expression/smiling, teeth visible) of children with healthy teeth, with visible untreated or treated caries (restorations/missing teeth as a consequence of caries treatment), each n = 13, were presented. First fixation, total fixation time and number of fixations on the areas of interest (eyes, nose, mouth) in the first two seconds of presentation were determined. Furthermore, the images were rated regarding arousal, valence and attractivity. Statistical analysis was performed using Mann Whitney-U- and Kruskal-Wallis-tests (alpha = 0.05). RESULTS: Generally, laypersons spent more time exploring and fixating the eye region than the mouth, while dental experts more often first percept and longer and more often fixated the mouth region, especially in images with emotional expression. Dental experts, but not laypersons, were significantly longer fixating the mouth of children with untreated caries than the mouth of children with healthy teeth in images with emotional expression. When evaluating images with emotional expression, both dental experts and laypersons rated children with healthy teeth to be more attractive, pleasant and calm than children with untreated or treated caries. CONCLUSIONS: Children with visible treated and untreated caries were differently perceived by laypersons and dental experts than children with healthy teeth. PMID- 29792912 TI - Heat shock protein B1 is required for the prolactin-induced cytoprotective effects on pancreatic islets. AB - The success of islet transplantation has improved lately. Unfortunately, it is still compromised by cell loss. We have shown that prolactin (PRL) inhibits beta cell apoptosis and up-regulates the antiapoptotic Heat Shock Protein B1 (HSPB1) in human islets. Since its function in pancreatic islets has not been studied, we explored the role of HSPB1 in PRL-induced beta-cell survival. The significant PRL induced cytoprotection in control cells was abrogated in HSPB1 silenced cells, overexpression of HSPB1 recovered survival. PRL-mediated inhibition of cytokine induced caspase activities and cytokine-induced decrease of BCL-2/BAX ratio was significantly reverted in knocked-down cells. Kinetics of HSPB1 and HSF1 expression were studied in primary cultures of murine and human pancreatic islets. These findings are highly relevant for the improvement of clinical islet transplantation success rate since our results demonstrated a key role for HSPB1 pointing it as a promising target for beta-cell cytoprotection through the up regulation of an endogenous protective pathway. PMID- 29792911 TI - Prolonged drug release properties for orodispersible films by combining hot-melt extrusion and solvent casting methods. AB - Orodispersible films (ODFs) are an advantageous dosage form to accomplish patient convenience and compliance in oral drug delivery. They provide a number of special application features, such as the ease of administration without water and suitability for patients with swallowing problems. However, this promising dosage form has been limited to immediate release formulations so far. The aim of this study was to develop a thin film produced by solvent casting, which is rapidly disintegrating when placed in the mouth, but which provides prolonged drug release characteristics by incorporating drug-loaded matrix particles (MPs). MPs were produced by hot-melt extrusion and subsequent milling, using theophylline anhydrous as model drug and Eudragit(r) RS as matrix-forming agent enabling prolonged drug release. ODFs were manufactured using hypromellose as film former. Dissolution studies were performed to investigate the kinetics and the duration of drug release. Additionally, disintegration time was determined using the PharmaTest(r) disintegration tester equipped with a specific sample holder for ODFs. All produced ODFs containing theophylline-loaded MPs show fast disintegration while the drug release was prolonged. The degree of release prolongation increases with increasing sizes of incorporated MPs. Matrix controlled release kinetics were found for ODFs containing MPs with at least 315 um in size. In summary, the production of fast disintegrating ODFs with prolonged release properties was feasible. Furthermore, freely adjustable dissolution profiles could be realized for ODFs by incorporating MPs of various particle sizes. PMID- 29792913 TI - Comparison of cerebral ventricular volumes and cortical thicknesses in normal rats and Genetic Absence Epilepsy (GAERS): A developmental study. AB - Ventricular enlargement and cortical atrophy have been associated with various central nervous system diseases. The aim of the present study was to measure the volumes of the lateral (LV) and third (3V) ventricles and to determine the cortical thickness for the motor (MCx), somatosensory (SSCx), visual (VCx) and auditory (AuCx) cortex and the striatum of Wistar rats, in a developmental series at 10, 20, 30, and 60 days postnatal, and to compare them with similar data from genetic absence epilepsy rats from Strasbourg (GAERS). Serial sections were taken from the brains of Wistar and GAERS animals and were Nissl stained. Photographs were taken from specific sections of the brain for measurements of ventricular volume, cortical and striatal thickness. The image-j computer program was used for the volume and thickness measurements. The data was statistically analyzed by 3-way ANOVA using SPSS 15. Comparison of the measurements of GAERS and Wistar animals showed no statistically significant differences at any of the developmental stages regarding the ventricular (LV and 3V) volumes. However, at P60 and P30 of the MCx, P30 of the SSCx, P20 of the VCx and AuCx showed a significantly thinner cortical thickness in the GAERS than in the Wistar animals. The striatal measurements showed significant decrease in thickness of the striatum at P30 and P60. Further, brain size measurements (between the two temporal poles) showed significant decrease in the size at P30 and P60 of GAERS animals. The presence of thinner cortical and striatal thicknesses and smaller brain size in GAERS animals may suggests that these changes could be involved in the mechanism of epileptogenicity or be a result of the epileptogenicity. PMID- 29792914 TI - Modulation of diverse oncogenic transcription factors by thymoquinone, an essential oil compound isolated from the seeds of Nigella sativa Linn. PMID- 29792916 TI - Flow cytometry-based method facilitates optimization of PMA treatment condition for PMA-qPCR method. AB - Coupling propidium monoazide (PMA) with quantitative PCR (PMA-qPCR) has been successfully applied to specific detection and quantification of viable cells in various samples. The optimal PMA treatment condition is usually determined through qPCR. However, it is a tedious, time consuming and costly process including DNA extraction and qPCR. To overcome this problem, a flow cytometry based (FCM-based) method was first proposed in this study to replace qPCR for screening of the optimal PMA treatment condition for Helicobacter pylori, since the pure culture treated with PMA was actually a single cell suspension with fluorescent dye. Results showed that the optimal PMA treatment condition (30 MUM of PMA and 8 min of exposure time) determined by the novel method was the same as that determined by the qPCR-based method, which demonstrate the feasibility of this approach. In addition, with the comparison of the qPCR-based method, the FCM based method allows screening of the optimal PMA treatment condition become much more simple, rapid and economical. PMID- 29792917 TI - Storage, visualization, and navigation of 3D genomics data. AB - The field of 3D genomics grew at increasing rates in the last decade. The volume and complexity of 2D and 3D data produced is progressively outpacing the capacities of the technology previously used for distributing genome sequences. The emergence of new technologies provides also novel opportunities for the development of innovative approaches. In this paper, we review the state-of-the art computing technology, as well as the solutions adopted by the platforms currently available. PMID- 29792918 TI - Translational -omics: Future potential and current challenges in precision medicine. AB - Rapid advances in computational science and biotechnology are paving the way for precision medicine - a vision in next-generation healthcare that promises to provide a care package uniquely tailored to each individual's molecular make-up. Until relatively recently, the focus has been firmly centred around the genome; however, over the past two decades there has been a surge in the study of molecular activity within other biological domains (proteome/transcriptome/metabolome) involved in health and pathogenesis. The term '-omics' is broadly applied to these disciplines and 'translational -omics' refers to clinical utilisation of data derived from these scientific approaches. Translational -omics represents the cornerstone of the precision medicine initiative and offers positively disruptive solutions in global healthcare from a humanitarian, scientific and economic standpoint. However, there are unique challenges anticipated for all stakeholders within the precision medicine community, and addressing these early on in the adoption of precision approaches is critical. Herein, we outline the potential for translational -omics in precision medicine, highlight key roadblocks to successful implementation and propose potential solutions to current and expected problems. PMID- 29792915 TI - The CD44-HA axis and inflammation in atherosclerosis: A temporal perspective. AB - Cardiovascular disease (CVD) due to atherosclerosis is a disease of chronic inflammation at both the systemic and the tissue level. CD44 has previously been implicated in atherosclerosis in both humans and mice. This multi-faceted receptor plays a critical part in the inflammatory response during the onset of CVD, though little is known of CD44's role during the latter stages of the disease. This review focuses on the role of CD44-dependent HA-dependent effects on inflammatory cells in several key processes, from disease initiation throughout the progression of atherosclerosis. Understanding how CD44 and HA regulate inflammation in atherogenesis is key in determining the utility of the CD44-HA axis as a therapeutic target to halt disease and potentially promote disease regression. PMID- 29792920 TI - Inner ear drug delivery: Recent advances, challenges, and perspective. AB - Effective and safe treatment of auditory and vestibular diseases has become increasingly dependent on inner ear drug delivery systems. This review highlights recent advances in inner ear drug delivery research and technologies. The focus is on strategies to overcome delivery barriers and to improve drug residence and targeting, with special attention to in vivo animal and human studies. The research in gene and stem cell delivery to the inner ear is briefly reviewed. Newly developed research tools to address experimental challenges and safety issues are discussed. Local drug delivery to the inner ear with non-invasive or minimally invasive approaches still remains challenging. Nanocarrier-based systems with sustained and targeted delivery properties may be promising for future clinical applications. Precisely controlled intratympanic and intracochlear administration with minimized trauma to the delicate inner ear represents the future perspective in inner ear drug research and development. Trans-oval window delivery may be promising as it allows direct delivery of drugs to the vestibule for vestibular disorders while avoiding the undesired effects due to drug distribution to the cochlea. PMID- 29792919 TI - Seeing the light: Shifting from wild rhizomes to extraction of active ingredients from above-ground parts of Paris polyphylla var. yunnanensis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizomes of Paris polyphylla var. yunnanensis are widely used in traditional Chinese medicine (TCM) as hemostatic, antitumor, and antimicrobial agents. More than 70 Chinese patent medicines are based on P. polyphylla var. yunnanensis rhizomes. Steroidal saponins are considered as the main active ingredients of these rhizomes. However, wild populations of P. polyphylla var. yunnanensis are greatly threatened due to the illegal wild harvest and over-utilization of the rhizomes. In contrast, the renewable above-ground parts (leaves and stems) of P. polyphylla var. yunnanensis are usually thrown away as waste material, whether from wild or cultivated material. AIM OF THE STUDY: The aim of this study was to use HPLC analyses of chemical constituents and bioactive assays to assess whether the above-ground parts could be an alternative source of active ingredients to the rhizomes of P. polyphylla var. yunnanensis. MATERIALS AND METHODS: The saponin components of the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were analyzed by HPLC-UV. The total saponins extracted from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were evaluated for their hemostatic, cytotoxic, and antimicrobial activities by using the rabbit blood in vitro based on turbidimetric method, MTT assay method, and a dilution antimicrobial susceptibility test method, respectively. RESULTS: Four bioactive spirostanol saponins (paris saponins I, II, VI, and VII) were detected in the total saponins from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis, which indicated they should have similar pharmacological properties. The bioactive assays revealed that both the parts of P. polyphylla var. yunnanensis exhibited the same hemostatic, cytotoxic, and antimicrobial effects. CONCLUSION: Our results revealed that based on saponin content in the above-ground parts of P. polyphylla var. yunnanensis and the requirements stipulated in 2015 of Chinese Pharmacopoeia, the above-ground parts (especially its leaves) can be an alternative and more sustainable source of active ingredients compared to the rhizomes. PMID- 29792921 TI - Characterization of solution stress degradation products of aliskiren and prediction of their physicochemical and ADMET properties. AB - Forced degradation studies on aliskiren were carried out according to ICH and WHO guidelines. Six degradation products were formed in total in the solution state. Their separation among themselves and from the drug was successfully achieved on a C-18 column utilizing acetonitrile and phosphate buffer (pH 3.0) in the mobile phase, which was run in a gradient mode. To characterize them, a complete mass fragmentation pathway of the drug was first established with the help of MS/TOF and MSn data. This was followed by LC-MS/TOF studies on the degradation products. Some of the degradation products were also isolated and subjected to 1D (1H, 13C and DEPT-135) and 2D (COSY, HSQC and HMBC) NMR studies for confirmation of their structures. An interesting observation was hydrolysis followed by cyclization in case of three degradation products. Also, acetonitrile was found to react with aliskiren, leading to formation of a pseudo degradation product. Additionally, comparative ADMET properties of the drug and degradation products were established using ADMET PredictorTM. PMID- 29792922 TI - Rapid resolution of multi-drug resistance bacterial genome harbouring mcr-1 and blaCMY-2 using MinION sequencing platform. PMID- 29792923 TI - High throughput sequencing identifies chilling responsive genes in sweetpotato (Ipomoea batatas Lam.) during storage. AB - Sweetpotato (Ipomoea batatas L.) is a globally important economic food crop. It belongs to Convolvulaceae family and origins in the tropics; however, sweetpotato is sensitive to cold stress during storage. In this study, we performed transcriptome sequencing to investigate the sweetpotato response to chilling stress during storage. A total of 110,110 unigenes were generated via high throughput sequencing. Differentially expressed genes (DEGs) analysis showed that 18,681 genes were up-regulated and 21,983 genes were down-regulated in low temperature condition. Many DEGs were related to the cell membrane system, antioxidant enzymes, carbohydrate metabolism, and hormone metabolism, which are potentially associated with sweetpotato resistance to low temperature. The existence of DEGs suggests a molecular basis for the biochemical and physiological consequences of sweetpotato in low temperature storage conditions. Our analysis will provide a new target for enhancement of sweetpotato cold stress tolerance in postharvest storage through genetic manipulation. PMID- 29792924 TI - Creation of an Acellular Vaginal Matrix for Potential Vaginal Augmentation and Cloacal Repair. AB - STUDY OBJECTIVE: Our aim was to use porcine vagina to create a vaginal matrix and test its cellular biocompatibility. DESIGN, SETTING, AND PARTICIPANTS: Vagina was harvested from pigs and decellularized (DC) using a combination of detergents (Triton X-100 and sodium deoxycholate) and enzymes (DNAse/RNAse). INTERVENTIONS: The presence of cellular material, collagen structural integrity, and basement membrane proteins were assessed histologically. To address cytocompatibility, porcine adipose-derived mesenchymal stem cells were harvested from abdominal fat together with vaginal epithelial cells and seeded onto the mucosal aspect of the vaginal scaffold. Both cell populations were seeded individually and assessed histologically at days 3 and 10. MAIN OUTCOME MEASURES AND RESULTS: The combination of enzymes and detergents resulted in a totally acellular matrix with very low DNA amount (control = 97.5 ng/MUL +/- 10.8 vs DC = 40.1 ng/MUL +/- 0.33; P = .02). The extracellular matrix showed retention of collagen fibers and elastin and a 50% retention in glycosaminoglycan content (control = 1.18 MUg/mg +/- 0.28; DC = 1.35 MUg/mg +/- 0.1; P = .03) and an intact basement membrane (positive for laminin and collagen IV). Seeded scaffolds showed cell attachment with adipose-derived mesenchymal stem cells and vaginal epithelial cells at days 3 and 10. CONCLUSION: It is possible to generate an acellular porcine vaginal matrix capable of supporting cells to reconstruct the vagina for future preclinical testing, and holds promise for creating clinically relevant-sized tissue for human application. PMID- 29792925 TI - Change in patient-reported outcomes in patients with and without mechanical symptoms undergoing arthroscopic meniscal surgery: A prospective cohort study. AB - OBJECTIVE: Patients with degenerative or traumatic meniscal tears are at high risk of developing knee osteoarthritis. We investigated if younger (<=40 years) and older (>40 years) patients with preoperative mechanical symptoms (MS) improved more in patient-reported outcomes after meniscal surgery than those without MS. DESIGN: Patients from Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing arthroscopic surgery for a meniscal tear completed online questionnaires before surgery, and at 12 and 52 weeks follow-up. Questionnaires included self-reported presence of MS (i.e., sensation of catching and/or locking) and the Knee injury and Osteoarthritis Outcome Score (KOOS). We analyzed between-group differences in change in KOOS4 from baseline to 52 weeks, using an adjusted mixed linear model. RESULTS: 150 younger patients (mean age 31 (SD 7), 67% men) and 491 older patients (mean age 54 (SD 9), 53% men) constituted the baseline cohorts. Patients with MS generally had worse self-reported outcomes before surgery. At 52 weeks follow-up, younger patients with preoperative MS had improved more in KOOS4 scores than younger patients without preoperative MS (adjusted mean difference 10.5, 95% CI: 4.3, 16.6), but did not exceed the absolute postoperative KOOS4 scores observed for those without MS. No difference in improvement was observed between older patients with or without MS (adjusted mean difference 0.7, 95% CI: -2.6, 3.9). CONCLUSIONS: Younger patients (<=40 years) with preoperative MS experienced greater improvements after arthroscopic surgery compared to younger patients without MS. Our observational study result needs to be confirmed in randomized trials. PMID- 29792926 TI - Prediction of midlife hand osteoarthritis in young men. AB - OBJECTIVES: Improved prediction modeling in osteoarthritis (OA) may encourage risk reduction through calculation of individual and population lifetime risks. There are currently no prediction models for hand OA. Thus, we aimed to 1) develop a prediction model for hand OA in men and 2) to contrast its discriminative performance to a prediction model for lung cancer and chronic obstructive pulmonary disease (COPD). METHODS: We included 40,118 men aged 18 years undergoing mandatory conscription in Sweden 1969-70. Incident hand OA and lung cancer/COPD were obtained from diagnostic codes in the Swedish National Patient Register 1987-2010, i.e., until subjects were 59 years of age. We studied the strongest candidate predictors from five domains; socioeconomic, local biomechanical, systemic, lifestyle-related and general health factors, using logistic regression with backward elimination of candidate predictors with P > 0.2 to determine final models. To avoid overfitting we used bootstrapping. RESULTS: The strongest predictors for hand OA were body mass index (BMI), elbow flexor strength, systolic blood pressure, lower education and sleep problems. We observed excellent agreement between observed and predicted values, yet the discrimination was moderate (Area Under the Curve [AUC] = 0.62, 95% CI = 0.58 0.64). The discrimination in the prediction model for lung cancer/COPD was good (AUC = 0.74, 95% CI = 0.72-0.76). CONCLUSION: This prediction model for hand OA was capable of discriminating between persons with and without hand OA to a similar extent that has been previously reported for knee OA. Still, prediction of OA is more challenging than for chronic pulmonary disease. PMID- 29792927 TI - Bacillus subtilis as probiotic candidate for red sea bream: Growth performance, oxidative status, and immune response traits. AB - The effects of dietary administration of Bacillus subtilis on the growth, digestive enzyme activity, blood chemistry, oxidative status and immune response of red sea bream (Pagrus major) were evaluated in the current study. Fish fed five different levels of B. subtilis at 0 (BS0), 1 * 104 (BS1), 1 * 106 (BS2), 1 * 108 (BS3) and 1 * 1010 (BS4) CFU kg-1 diet for 60 days. The obtained results showed that B. subtilis supplementation significantly improved growth performance (FBW, WG and SGR), feed utilization (FI, FCE, PER and PG) and whole-body protein content when compared to the control group (P < 0.05). Furthermore, the specific activities of amylase, protease and lipase enzymes up regulated significantly upon B. subtilis incorporation in red sea bream diets (P < 0.05). No changes have been reported on blood biochemical variables except for the plasma total protein, which increased significantly in fish fed BS3 diet when compared with the control diet (P < 0.05). Hematocrit, hemoglobin and the nitro blue tetrazolium values also reported the highest values significantly in fish fed B. subtilis, especially in case of BS3 and BS4 diets (P < 0.05). Serum bactericidal activity enhanced significantly in BS2, BS3 and BS4 groups (P < 0.05), while mucus bactericidal activity showed no significant activity among tested groups (P > 0.05). Serum lysozyme activity exhibited higher values in case of BS3 and BS4 groups than BS0 group (P < 0.05), while mucus lysozyme activity increased only in BS3 group. Also, serum peroxidase activity enhanced significantly in fish fed BS2 and BS3 diets (P < 0.05), however, no activities were observed in the collected mucus. All groups reflexed high tolerance ability against oxidative stress except for BS0 and BS1 groups. Additionally, catalase activity increased significantly in all B. subtilis fed groups when compared to BS0 group (P < 0.05). Considering the obtained results, the supplementation of B. subtilis in the diet of red sea bream at 1 * 108 and 1 * 1010 CFU kg-1 diet could improve the growth, feed utilization, health condition and immune response. PMID- 29792928 TI - Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress. AB - Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G4C2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G4C2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. PMID- 29792929 TI - Recent advances in intra-articular drug delivery systems for osteoarthritis therapy. AB - Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections. This paper reviews the role and interaction among different tissues involved in OA and summarizes recent clinical trials and research on DDSs, focusing on small molecule delivery. To achieve an ideal treatment, various key criteria have been identified to design and develop an IA DDS matching the clinical needs. PMID- 29792930 TI - Functional genomics for the oleaginous yeast Yarrowia lipolytica. AB - Oleaginous yeasts are valuable systems for biosustainable production of hydrocarbon-based chemicals. Yarrowia lipolytica is one of the best characterized of these yeast with respect to genome annotation and flux analysis of metabolic processes. Nonetheless, progress is hampered by a dearth of genome-wide tools enabling functional genomics. In order to remedy this deficiency, we developed a library of Y. lipolytica insertion mutants via transposon mutagenesis. The Hermes DNA transposon was expressed to achieve saturation mutagenesis of the genome. Over 534,000 independent insertions were identified by next-generation sequencing. Poisson analysis of insertion density classified ~ 22% of genes as essential. As expected, most essential genes have homologs in Saccharomyces cerevisiae and Schizosaccharomyces pombe, and the majority of those are also essential. As an obligate aerobe, Y. lipolytica has significantly more respiration - related genes that are classified as essential than do S. cerevisiae and S. pombe. Contributions of non-essential genes to growth in glucose and glycerol carbon sources were assessed and used to evaluate two recent genome-scale models of Y. lipolytica metabolism. Fluorescence-activated cell sorting identified mutants in which lipid accumulation is increased. Our findings provide insights into biosynthetic pathways, compartmentalization of enzymes, and distinct functions of paralogs. This functional genomic analysis of the oleaginous yeast Y. lipolytica provides an important resource for modeling, bioengineering, and design of synthetic minimalized strains of respiratory yeasts. PMID- 29792931 TI - Engineering the production of dipicolinic acid in E. coli. AB - Dicarboxylic acids, such as the phthalic acids and their derivatives, are monomeric components in several important polyesters and polyamides. In most cases, these compounds are derived from fossil fuels and are not easily biodegradable. Dipicolinic acid (DPA) is a biologically derived aromatic di-acid that has a similar structure to isophthalic acid. Furthermore, DPA has been shown to give rise to polyesters, is readily biodegradable, and is non-toxic. DPA is naturally produced by Bacillus and Clostridium species during sporulation and can comprise up to 15% of the dry weight of bacterial spores. In this paper we demonstrate the first heterologous production of DPA and identify the genes appropriate for gram-scale production in the industrial workhorse organism, E. coli. Initially, several combinations of genes from the lysine pathway, including lysC, asd, dapA, and dapB, were overexpressed to determine which genes are necessary for recombinant production in E. coli. The in vitro activity of dipicolinate synthase was then compared between Bacillus subtilis and Clostridium perfringens. Next, in order to improve DPA production from glucose, an optimized strain was created that lacked several genes (lysA, tdh, and metA), resulting in 5.21 g/L DPA when 5 g/L of aspartate was supplied. Then, several aspartate kinases and dipicolinate synthases were screened for optimal activity in E. coli. The optimal genes were combined with the overexpression of phosphoenolpyruvate carboxylase to develop a full biosynthetic pathway capable of producing a titer of 4.7 g/L DPA directly from glucose. In summary, we have performed a detailed biochemical study of the key pathway enzyme dipicolinate synthase and achieved scalable heterogeneous production of DPA in the workhorse organism E. coli. PMID- 29792932 TI - Cystine/glutamate transporter, system xc-, is involved in nitric oxide production in mouse peritoneal macrophages. AB - The amino acid transport system xc- is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system xc-, xCT, is strongly induced by various stimuli, including oxidative stress and bacterial lipopolysaccharides (LPS) in macrophages. In the present study, we investigated the production of nitric oxide by LPS-stimulated mouse peritoneal macrophages isolated from both xCT-deficient and wild-type mice. After culturing macrophages in the presence of LPS for 24-48 h, nitrite levels in the medium of xCT-deficient macrophages were significantly decreased compared to that of wild type cells. However, the transport activity of arginine, a precursor of nitric oxide, and the expression of nitric oxide synthase 2 in xCT-deficient macrophages were similar to those of wild-type cells. When wild-type macrophages were cultured in the medium that contained no cystine, nitric oxide production was decreased to the level similar to that of the xCT-deficient macrophages. When xCT deficient macrophages were cultured with 2-mercaptoethanol, intracellular cysteine levels were increased and nitrite accumulation in the medium was significantly increased. On the other hand, when these cells were cultured with buthionine sulfoximine, an inhibitor of glutathione synthesis, nitrite accumulation in the medium was essentially unchanged, although intracellular glutathione levels were very low. Reactive oxygen species levels in xCT-deficient macrophages were higher than those of wild-type cells, and treatment with LPS caused an increase in oxidative stress in both cells. These results suggest that intracellular cysteine supplied by xCT contributes to nitric oxide production and the reduction of oxidative stress in macrophages. PMID- 29792933 TI - Role of neuronal nitric oxide synthase in slowly progressive dopaminergic neurodegeneration in the Zitter rat. AB - Neuronal nitric oxide synthase (nNOS) is involved in nigrostriatal dopaminergic (DA) neurodegeneration. However, little is known about the distribution patterns and functions of nNOS in slowly progressive DA neurodegeneration. Here we describe the spatiotemporal change in nNOS expression over the course of neurodegeneration and the effect of short- or long-term treatment with the nNOS inhibitor, 7-nitroindazole (7-NI), in zitter (zi/zi) rats. In the substantia nigra pars compacta (SNc), nNOS expression was significantly increased with progression of neurodegeneration. nNOS-immunoreactive (ir) cells were in the vicinity of tyrosine hydroxylase-ir (TH-ir) DA neurons, and some of these cells were also positive for calbindin. nNOS in the caudate-putamen (CPu) showed little difference during progression of neurodegeneration. However, immunoelectron microscopic analysis revealed that abundant TH-ir fibers in the CPu were degenerated due to compression by vacuoles that contained swollen neuronal and glial elements. Additionally, lipid peroxidation as a marker of membrane oxidation was significantly increased in zi/zi rats. Short-term 7-NI treatment attenuated the increase in lipid peroxidation and inhibited the vacuolation in the CPu. Moreover, long-term 7-NI treatment significantly protected TH-ir neurons in the SNc, and TH-ir fibers and DA contents in the CPu. These results show that nNOS exacerbates slowly progressive DA neurodegeneration, and the neuroprotective effects of 7-NI may result from suppression of membrane oxidation that causes abnormal membrane structures in zi/zi rats. PMID- 29792934 TI - Pretarsal skin height changes in children receiving topical prostaglandin analogue therapy for primary congenital glaucoma. AB - PURPOSE: To compare pretarsal skin height (PTSH), as proxy indicator of deepening of the upper eyelid sulcus, in children with primary congenital glaucoma (PCG) treated with topical prostaglandin analogues (PGAs) with PTSH in healthy children (control group 1) and children with PCG but not using PGAs (control group 2). METHODS: We recruited children with PCG who had been using PGAs for at least 6 months (PCG/PGA group). PTSH in all participants was measured using ImageJ software from photographs taken in a standardized manner. The PTSH was compared for the PCG group and both control groups. RESULTS: A total of 34 children with PCG and 41 controls (31 in group 1; 10 in group 2) were included. The difference in PTSH between children in the PCG/PGA group and both control groups was statistically significant (mean difference, >=1.7 mm [P < 0.01]). CONCLUSIONS: The PTSH was significantly greater in children with PCG using PGAs compared to children with PCG not using PGAs and healthy children. Children and their parents should be counseled about lid abnormalities prior to commencing treatment with PGAs. PMID- 29792936 TI - Efficient Detection of Copy Number Mutations in PMS2 Exons with a Close Homolog. AB - Detection of 3' PMS2 copy-number mutations that cause Lynch syndrome is difficult because of highly homologous pseudogenes. To improve the accuracy and efficiency of clinical screening for these mutations, we developed a new method to analyze standard capture-based, next-generation sequencing data to identify deletions and duplications in PMS2 exons 9 to 15. The approach captures sequences using PMS2 targets, maps sequences randomly among regions with equal mapping quality, counts reads aligned to homologous exons and introns, and flags read count ratios outside of empirically derived reference ranges. The method was trained on 1352 samples, including 8 known positives, and tested on 719 samples, including 17 known positives. Clinical implementation of the first version of this method detected new mutations in the training (N = 7) and test (N = 2) sets that had not been identified by our initial clinical testing pipeline. The described final method showed complete sensitivity in both sample sets and false-positive rates of 5% (training) and 7% (test), dramatically decreasing the number of cases needing additional mutation evaluation. This approach leveraged the differences between gene and pseudogene to distinguish between PMS2 and PMS2CL copy-number mutations. These methods enable efficient and sensitive Lynch syndrome screening for 3' PMS2 copy-number mutations and may be applied similarly to other genomic regions with highly homologous pseudogenes. PMID- 29792935 TI - LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys. AB - LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks. Treatment with LP533401 decreased serotonin turnover and restored bone mineral status, microarchitecture, and strength in CKD rats to the values observed in the controls. In parallel with the reduction of serotonin, serum phosphate levels also decreased, particularly in the LP533401, 100 mg/kg group. The mechanism underlying this phenomenon resulted from decreased expression of the renal VDR/FGF1R/Klotho/Npt2a/Npt2c axis, leading to elevated phosphate excretion in the kidneys. The elevated urinary phosphate excretion resulted in improved bone mineral status and strength in LP533401-treated rats. Unexpectedly, the standard VEH used in this model was able to reduce renal VDR/FGF1R/Klotho/Npt2a expression, leading to a compensatory increase in Npt2c mRNA levels, secondary disturbances in phosphate-regulated hormones and partial improvement in the mineral status of the trabecular bone. The decrease of serotonin synthesis together with the simultaneous reduction of renal Npt2a and Npt2c expression in rats treated with LP533401, 100 mg/kg led to an increase in 1,25(OH)2D3 levels; this mechanism seems to be particularly beneficial in relation to the mineral status of cortical bone. PMID- 29792938 TI - Sella Turcica Bridging As A Predictor Of Class II Malocclusion-An Investigative Study. AB - BACKGROUND: Sella turcica, the bony depression located in sphenoid bone houses and protects the pituitary gland. Formation and development of the sella turcica and teeth share, in common, the involvement of neural crest cells. The anterior part of the sella turcica is believed to develop mainly from neural crest cells, and dental epithelial progenitor cells differentiate through sequential and reciprocal interaction with neural crest-derived mesenchyme. Thus, any structural deviations in the sella, like bridging or roofing, are believed to be related to specific deviations in the facial skeleton and dental anomalies. Until now, there have been no studies concerning the prevalence of sella turcica bridging in skeletal Class II subjects. OBJECTIVE: The aim of this study was to analyse the prevalence of sella turcica bridging in subjects with class I and class II skeletal types and to check whether sella can be considered as diagnostic marker for skeletal class II malocclusion. MATERIALS AND METHODS: Lateral cephalometric images of 205 subjects in the age range of 13 to 25 years were retrospectively analysed and classified for the type of skeletal malocclusion and the radiographs were evaluated for the prevalence of bridging of the sella in these subjects. RESULTS: The results show significance in the prevalence of sella turcica bridging (partial/complete) among subjects with skeletal class II malocclusion. PMID- 29792937 TI - A Reliable Targeted Next-Generation Sequencing Strategy for Diagnosis of Myopathies and Muscular Dystrophies, Especially for the Giant Titin and Nebulin Genes. AB - Myopathies and muscular dystrophies (M-MDs) are genetically heterogeneous diseases, with >100 identified genes, including the giant and complex titin (TTN) and nebulin (NEB) genes. Next-generation sequencing technology revolutionized M MD diagnosis and revealed high frequency of TTN and NEB variants. We developed a next-generation sequencing diagnostic strategy targeted to the coding sequences of 135 M-MD genes. Comparison of two targeted capture technologies (SeqCap EZ Choice library capture kit and Nextera Rapid Capture Custom Enrichment kit) and of two whole-exome sequencing kits (SureSelect V5 and TruSeq RapidExome capture) revealed best coverage with the SeqCap EZ Choice protocol. A marked decrease in coverage was observed with the other kits, affecting mostly the first exons of genes and the repeated regions of TTN and NEB. Bioinformatics analysis strategy was fine-tuned to achieve optimal detection of variants, including small insertions/deletions (INDELs) and copy number variants (CNVs). Analysis of a cohort of 128 patients allowed the detection of 52 substitutions, 13 INDELs (including a trinucleotide repeat expansion), and 3 CNVs. Two INDELs were localized in the repeated regions of NEB, suggesting that these mutations may be frequent but underestimated. A large deletion was also identified in TTN that is, to our knowledge, the first published CNV in this gene. PMID- 29792939 TI - Impact of antithrombotic treatment in orbital haematoma. AB - INTRODUCTION: Orbital haematomas threaten the visual prognosis, but no treatment guidelines have been proposed. Antithrombotics could affect their prognosis and treatment. This study aimed to evaluate the effect of antithrombotics in the management of orbital haematomas and to suggest a standardised protocol. MATERIAL AND METHODS: We conducted a retrospective study by sending a standardised questionnaire to 20 French maxillofacial surgery university departments to collect all the cases of orbital haematoma. RESULTS: Twenty-five cases from 10 centres were collected, including five patients treated with anticoagulant and one patient treated with dual antiplatelet. Antithrombotics increased the risk of amaurosis and ocular disorders significantly. Surgery was performed for 66.7% of patients treated with antithrombotic and for 89.5% of other patients. Surgical delay was longer in patients treated with antithrombotic. Surgical drainage was used in most of the cases, whereas canthotomy with inferior cantholysis was the least-used technique. CONCLUSION: Antithrombotics appear to worsen the functional prognosis of orbital haematomas. A surgical management of orbital haematoma in patients treated with antithrombotics is not contraindicated. Surgical delay must be shortened as much as possible. A lateral canthotomy with inferior cantholysis seems to be an appropriate solution. PMID- 29792942 TI - Optimisation of decontamination method and influence of culture media on the recovery of Mycobacterium avium subspecies paratuberculosis from spiked water sediments. AB - : The recovery of Mycobacterium avium subspecies paratuberculosis (Map) from the environment can be a laborious process - owing to Map being fastidious, its low number, and also high numbers of other microbial populations in such settings. Protocols i.e. filtration, decontamination and modified elution were devised to recover Map from spiked water sediments. Three culture media: Herrold's Egg Yolk Media (HEYM), Middlebrook 7H10 (M-7H10) and Bactec 12B were then employed to grow the organism following its elution. In the sterile sediment samples the recovery of Map was significant between the time of exposure for each of HEYM and M-7H10, and insignificant between both media (P < 0.05). However, in the non-sterile sediment samples, the HEYM grew other background microflora including moulds at all the times of exposure whilst 4 h followed by M-7H10 culture yielded Map colonies without any background microflora. Using sterile samples only for the Bactec 12B, the recovery of Map decreased as time of exposure increased. Based on these findings, M-7H10 should be considered for the recovery of Map from the natural environment including water sediments where the recovery of diverse microbial species remains a challenge. SIGNIFICANCE OF THE STUDY: Map is a robust pathogen that abides in the environment. In water treatment operations, Map associates with floccules and other particulate matter including sediments. It is also a fastidious organism, and its detection and recovery from the water environment is a laborious process and can be misleading within the abundance of other mycobacterial species owing to their close resemblance in phylogenetic traits. In the absence of a reliable recovery method, Map continues to pose public health risks through biofilm in household water tanks, hence the need for the development of a reliable recovery protocol to monitor the presence of Map in water systems in order to curtail its public health risks. PMID- 29792941 TI - In-situ analysis of grain rotation and lattice strain within a magnesium polycrystal based on synchrotron polychromatic X-ray diffraction technique: (I) prior to twin. AB - Hexagonal-close-packed structure aggregates exhibit complicated deformation behaviors, involving different slips and twinning. Synchrotron polychromatic X ray microdiffraction (micro-XRD) was utilized to study in situ an extruded Mg-3Al 1Zn strip subjected to uniaxial tension. The evolution of grain rotation and lattice strain was analyzed under the load levels from 12 to 73 MPa. The micro XRD data was used to map an area of 396 * 200 MUm within the region of interest. The experimental set-up and X-ray diffraction microscopy in two dimensions allow the morphology, orientation and strain of the target grain to be determined at the submicron size. Results depict local orientation fluctuation, lattice strain evolution, slips system and elastic modulus within the same grain. As the applied load increases, the grain's rotation is accelerated between 46 MPa and 51 MPa at which level of load the grain-scale plastic deformation is activated. The predominantly slip modes prior to twin are identified as the combination of b1-> = (0002) [112-0] andb3-> = (0002) [2-110]. During the inspection, all reflection planes displayed an onset of micro yielding at the macro load level of ~38 MPa. In this work, we confirm that magnesium is nearly elastic isotropic. PMID- 29792943 TI - The development of a screening protocol for Salmonella spp. and enteropathogenic Yersinia spp. in samples from wild boar (Sus scrofa) also generating MLVA-data for Y. enterocolitica and Y. pseudotuberculosis. AB - Salmonellosis and yersiniosis are notifiable human diseases that are commonly associated with contaminated food. Domestic pigs as well as wild boars and other wild-life have been identified as reservoirs of these bacteria. Methods for cultivation and molecular epidemiological investigations of Salmonella spp. are well established, however, cultivation of enteropathogenic Yersinia spp. is time- consuming and the commonly used method for molecular epidemiological investigations, pulsed-field gel electrophoresis, lack in discriminatory power. The aim of this study was to develop and evaluate a screening protocol well suited for wildlife samples and other highly contaminated samples. The method is based on PCR-screening followed by Multiple Loci Variant number tandem repeat Analysis (MLVA) on enrichment broth to obtain molecular epidemiological data for enteropathogenic Yersinia spp. without the need for pure isolates. The performance of the protocol was evaluated using wild boar samples (n=354) including tonsils, faeces and lymph nodes from 90 Swedish wild boars. The new protocol performed as well as or better than the established ISO-standards for detection and cultivation of Y. enterocolitica and Salmonella spp., however for cultivation of Y. pseudotuberculosis, further development is needed. The selection for motility seems beneficial for the enrichment of Salmonella spp. and Y. enterocolitica. Further, the selective enrichment prior to PCR-analysis eliminates inhibitory factors present in the original sample. In total, ten isolates of Y. enterocolitica of various bio-serotypes were obtained, and the MLVA-profile of these isolates were consistent with the profiles from the corresponding enrichment broth. Further, 22 isolates of Salmonella spp. comprising six different serovars were obtained with S. Fulica, S. Hadar and a monophasic S. Typhimurium being the most common. In conclusion, the presented screening protocol offers a rapid and efficient way to obtain prevalence data from a large sample set as well as MLVA-data within a short time frame. These results can hence improve the knowledge on the epidemiology and distribution of these pathogens and their importance to public health. PMID- 29792940 TI - A randomized control trial to determine the effectiveness and physiological effects of spinal manipulation and spinal mobilization compared to each other and a sham condition in patients with chronic low back pain: Study protocol for The RELIEF Study. AB - BACKGROUND: Low back pain (LBP) is one of the most common reasons for seeking medical care. Manipulative therapies are a common treatment for LBP. Few studies have compared the effectiveness of different types of manipulative therapies. Moreover, the physiologic mechanisms underlying these treatments are not fully understood. Herein, we present the study protocol for The Researching the Effectiveness of Lumbar Interventions for Enhancing Function Study (The RELIEF Study). METHODS AND STUDY DESIGN: The RELIEF Study is a Phase II RCT with a nested mechanistic design. It is a single-blinded, sham-controlled study to test the mechanisms and effectiveness of two manual therapy techniques applied to individuals (n = 162; 18-45 years of age) with chronic LBP. The clinical outcome data from the mechanistic component will be pooled across experiments to permit an exploratory Phase II RCT investigating the effectiveness. Participants will be randomized into one of three separate experiments that constitute the mechanistic component to determine the muscular, spinal, and cortical effects of manual therapies. Within each of these experimental groups study participants will be randomly assigned to one of the three treatment arms: 1) spinal manipulation, 2) spinal mobilization, or 3) sham laser therapy. Treatments will be delivered twice per week for 3-weeks. DISCUSSION: This data from this will shed light on the mechanisms underlying popular treatments for LBP. Additionally, the coupling of this basic science work in the context of a clinical trial will also permit examination of the clinical efficacy of two different types of manipulative therapies. PMID- 29792944 TI - Enrichment of low-density symbiont DNA from minute insects. AB - Symbioses between bacteria and insects are often associated with changes in important biological traits that can significantly affect host fitness. To a large extent, studies of these interactions have been based on physiological changes or induced phenotypes in the host, and the genetic mechanisms by which symbionts interact with their hosts have only recently become better understood. Learning about symbionts has been challenging in part due to difficulties such as obtaining enough high quality genomic material for high throughput sequencing technology, especially for symbionts present in low titers, and in small or difficult to rear non-model hosts. Here we introduce a new method that substantially increases the yield of bacterial DNA in minute arthropod hosts, and requires less starting material relative to previous published methods. PMID- 29792945 TI - Cross-linking by epichlorohydrin and diepoxybutane correlates with cytotoxicity and leads to apoptosis in human leukemia (HL-60) cells. AB - The bifunctional alkylating agents epichlorohydrin (ECH) and diepoxybutane (DEB) have been linked to increased cancer risks in industrial workers. These compounds react with DNA and proteins, leading to genotoxic effects. We used the comet assay to monitor formation of cross-links in HL-60 cells treated with ECH, DEB, and the structurally related anti-cancer drug mechlorethamine (HN2). We report a time- and dose-dependent cytotoxicity that correlated with cross-linking activity, following the order HN2 > DEB > ECH. The rate of cross-link repair also varied with drug, with ECH-induced lesions the fastest to repair. High drug doses led to the formation of saturating amounts of HN2 cross-links that were repaired inefficiently. DEB and ECH produced fewer overall cross-links, but some were also resistant to repair. These persistent cross-links may activate cell-cycle arrest to allow repair of damage, with prolonged arrest triggering apoptosis. Quantitative reverse transcription polymerase chain reaction experiments revealed that treatment of HL-60 cells with DEB and ECH results in up-regulation of several genes involved in the intrinsic (mitochondrial) apoptosis pathway, including BAX, BAK1, CASP-9, APAF-1, and BCL-2. These findings contribute to our understanding of the principles underlying the carcinogenic potentials of these xenobiotics. PMID- 29792946 TI - Investigation of nonalcoholic fatty liver disease-induced drug metabolism by comparative global toxicoproteomics. AB - Non-alcoholic fatty liver disease (NAFLD) includes conditions such as steatosis, non-alcoholic steatohepatitis, and ultimately hepatocellular carcinoma. Although the pathology of NAFLD is well-established, NAFLD-induced drug metabolism mediated by cytochrome P450 (CYP) in the liver has remained largely unexplored. Therefore, we investigated NAFLD-induced drug metabolism mediated by CYP by quantitative toxicoproteomics analysis. After administration of a methionine choline deficient (MCD) diet to induce development of NAFLD, tandem mass tags based liquid chromatography-tandem mass spectrometry analysis was conducted to investigate the dynamics of hepatic proteins. A total of 1295 proteins were identified, of which 934 were quantified by proteomic analysis. Among these proteins, 21 proteins were up-regulated and 51 proteins were down-regulated by the MCD diet. Notably, domain annotation enrichment using InterPro indicated that proteins related to CYPs were significantly decreased. When we investigated CYP activity using in vivo and in vitro CYP cocktail assays, most CYPs were significantly decreased, whereas CYP2D was not changed after administration of the MCD diet. In conclusion, we identified significantly altered levels of CYPs and their activities induced by the MCD diet and confirmed the NAFLD-induced drug metabolism by pharmacokinetic analysis. PMID- 29792947 TI - TRAIL attenuates sulforaphane-mediated Nrf2 and sustains ROS generation, leading to apoptosis of TRAIL-resistant human bladder cancer cells. AB - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can preferentially initiate apoptosis in malignant cells with minimal toxicity to normal cells. Unfortunately, many human cancer cells are refractory to TRAIL induced apoptosis through many unknown mechanisms. Here, we report that TRAIL resistance can be reversed in human bladder cancer cell lines by treatment with sulforaphane (SFN), a well-known chemopreventive isothiocyanate in various cruciferous vegetables. Combined treatment with SFN and TRAIL (SFN/TRAIL) significantly induced apoptosis concomitant with activation of caspases, loss of mitochondrial membrane potential (MMP), Bid truncation, and induction of death receptor 5. Transient knockdown of Bid prevented collapse of MMP induced by SFN/TRAIL, consequently reducing apoptotic effects. Furthermore, SFN increased both the generation of reactive oxygen species (ROS) and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is an anti-oxidant enzyme. Interestingly, TRAIL effectively suppressed SFN-mediated nuclear translocation of Nrf2, and the period of ROS generation was more extended compared to that of treatment with SFN alone. In addition, silencing of Nrf2 increased apoptosis in cells treated with SFN/TRAIL; however, blockade of ROS generation inhibited apoptotic activity. These data suggest that SFN-induced ROS generation promotes TRAIL sensitivity and SFN can be used for the management of TRAIL-resistant cancer. PMID- 29792948 TI - Comparative transcriptome analysis reveals significant differences in gene expression between appressoria and hyphae in Colletotrichum gloeosporioides. AB - Fruit rot caused mainly by Colletotrichum gloeosporioides is a major cause of pre and/or post-harvest diseases, which seriously constrains production, marketing, and export of fruits. To infect the host, this fungus evolves a specialized infection structure called the appressorium. Extensive past studies have characterized many appressorium-related genes in C. gloeosporioides, separately. However, a comprehensive understanding of the genes contributing to appressorium formation is far from complete. Here, global changes in gene expression were analyzed between appressoria and hyphae using RNA-Seq. We identified 4071 genes that are up-regulated in appressorium and discovered 468 unigenes that are expressed only in appressoria, compared with the fungal hyphae. Differentially expressed genes between appressoria and hyphae were assigned to 107 KEGG pathways, including metabolic pathways, secondary metabolite biosynthesis, molecular transport and signal transduction. Fourteen putative ABC transporter genes are significantly up-regulated in appressoria, and in contrast, twenty-six down-regulated. One hundred and one transcription factor genes show more than a 2 fold up-regulation in appressoria compared to hyphae. The up-regulation of 39 secreted protein candidates is observed, suggesting they may play important roles in initial infection processes. Our data demonstrate that appressorium development of C. gloeosporioides is accompanied by significant changes in gene expression, which provides novel insights to elucidate how this fungus regulates its development, pathogenicity and immune evasion. PMID- 29792949 TI - sRNAome and transcriptome analysis provide insight into chilling response of cowpea pods. AB - Cowpea is an important horticultural crop in tropical and subtropical areas of Asia, Africa, and Latin America, as well as parts of southern Europe and Central and South America. Chilling injury is a common physiological hazard of cowpea in cold chain logistics which reduce the cowpea pod's nutritional quality and product value. However, the molecular mechanism involved in chilling injury remains unclear in cowpea pods. RNA-Seq and sRNA-Seq technologies were employed to decipher the miRNAs and mRNAs expression profiles and their regulatory networks in cowpea pods involved in chilling stress. Differentially expressed miRNAs and mRNA profiles were obtained based on cluster analysis, miRNAs and target genes were found to show coherent relationships in the regulatory networks of chilling injury. Furthermore, we found that numerous miRNAs and nat-siRNAs' targets were predicted to be key enzymes involved in the redox reactions such as POD, CAT, AO and LOX, energy metabolism such as ATPase, FAD and NAD related enzymes and different transcription factors such as WRKY, bHLH, MYB, ERF and NAC which play important roles in chilling injury. PMID- 29792950 TI - Transcriptome profile analysis reveals the ontogenesis of rooted chichi in Ginkgo biloba L. AB - The Ginkgo biloba L. chichi is a unique organ. To explore the molecular mechanisms underlying the ontogenesis of G. biloba chichi, we used RNA-seq to analyse the transcriptome profile of rooted chichi at two developmental stages (ch1 and ch2) and nearby tissues (ck), and each sample had three biological replicates. A total of 57.74 Gb of clean bases were generated in nine cDNA libraries. These bases were de novo assembled into 68,277 unigenes with average length of 844 bp, and 51.47% of the unigenes had a match in at least one public database. The differentially expressed genes (DEGs) in ch1 vs. ck and ch2 vs. ck were 2748 and 8594, respectively. The DEGs involved in the auxin signal pathway, auxin polar transport, storage-related proteins, and the cell cycle pathway might play roles in the ontogenesis of chichi. The quantitative real-time PCR results were closely correlated with transcriptome data. The transcriptome resources generated in the current study provide gene expression profiles and differential expression profiles of G. biloba chichi and offer an essential resource to probe the molecular mechanisms underlying the ontogenesis of G. biloba chichi. PMID- 29792952 TI - Anticancer mechanism of Sinapic acid in PC-3 and LNCaP human prostate cancer cell lines. AB - Sinapic acid (SA) is a derivative of hydroxycinnamic acid and found in various vegetables and fruit species. Aim was to evaluate the anticancer effects of SA in PC-3 and LNCaP human prostate cancer cells. The effect of SA on cell viability was determined using XTT assay. Expressions of 8 genes for apoptosis and 6 genes for metastasis were evaluated by qPCR. Caspase-3 activity was determined using caspase-3 colorimetric assay kit. Effect of SA on cell invasion was evaluated with cell invasion assay. The IC50 dose of SA in PC-3 and LNCaP cells was found to be 1000 MUM for 72 h. SA treatment increased the expression of BAX, CASP3, CASP8, CYCS, FAS, TIMP-1 and CDH1 however significant decreased the expression of MMP-9 in PC-3 cells. In LNCaP cells, the expressions of BAX, CASP3, CASP7 and CYCS were significantly elevated; however, a decrease was seen in the expressions of CDH2, MMP-2 and MMP-9 in the SA treatment. Moreover, SA significantly increased caspase-3 activity and suppressed the cell invasion. In conclusion, it is thought that SA has anticancer effect on prostate cancer cells. However, more detailed studies should be conduct to illuminate molecular mechanism of apoptotic and antimetastatic activity of SA. PMID- 29792953 TI - Protective effect of S-nitrosoglutathione administration against hyperglycemia induced disruption of blood brain barrier is mediated by modulation of tight junction proteins and cell adhesion molecules. AB - Diabetes is associated with increased blood brain barrier (BBB) permeability resulting in neurological deficits. The present study investigated the role of S nitrosoglutathione (GSNO) on tight junction proteins and cell adhesion molecules in streptozotocin-induced diabetic mice. Diabetes was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) for 5 days in mice. GSNO was administered daily (100 MUg/kg body weight, orally) for 8 weeks after the induction of diabetes. A significant decline was observed in the cognitive ability of diabetic animals assessed using radial arm maze test. A significant increase was observed in nitrotyrosine levels in cortex and hippocampus of diabetic mice. Relative mRNA and protein expression of tight junction proteins viz; zona occludens-1 (ZO-1) and occludin were significantly lower in the microvessels isolated from cortex and hippocampus of diabetic animals, whereas expression of claudin-5 was unaltered. Immunofluorescence of tight junction proteins confirmed loss of ZO-1 and occludin in the diabetic brain. Furthermore, significant increase in interstitial cell adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mRNA and protein levels was observed in diabetic animals. Ultrastructure of microvessels from diabetic brain was also altered thereby confirming BBB disruption. GSNO administration to diabetic animals, on the other hand, was able to ameliorate loss of ZO-1 and occludin as well as normalize ICAM-1 and VCAM-1 expression, restore BBB integrity, and improve cognitive deficits. The findings clearly suggest that GSNO is a therapeutic molecule with potential to protect BBB and prevent diabetes induced neurological deficits. PMID- 29792954 TI - Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection. AB - Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle. Animals were then euthanized at various time points for immunohistochemistry, gene expression, and lipidomic analyses. Peak microglial activation was observed at 5 days post surgery and the resolution index was 10 days. Of the approximately 350 genes significantly changed over the 28 days post LPS injection, 130 were uniquely changed at 3 days post injection. No changes were observed in the bioactive mediator pools. However, a few lysophospholipid species were decreased at 24hr post surgery. When brain DHA is increased, microglial cell density did not resolve faster and did not alter gene expression. In conclusion, resolution of neuroinflammation appears to be independent of SPM. Increasing brain DHA had no effect in this model. PMID- 29792955 TI - Fisetin alleviates oxidative stress after traumatic brain injury via the Nrf2-ARE pathway. AB - Fisetin, a natural flavonoid, has neuroprotection properties in many brain injury models. However, its role in traumatic brain injury (TBI) has not been fully explained. In the present study, we aimed to explore the neuroprotective effects of fisetin in a mouse model of TBI. We found that fisetin improved neurological function, reduced cerebral edema, attenuated brain lesion and ameliorated blood brain barrier (BBB) disruption after TBI. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fisetin treatment. Furthermore, administration of fisetin suppressed neuron cell death and apoptosis, increased the expression of B-cell lymphoma 2 (Bcl-2), while decreased the expression of Bcl-2-associated X protein (Bax) and caspase-3 after TBI. In addition, fisetin activated the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway following TBI. However, fisetin only failed to suppress oxidative stress in Nrf2-/- mice. In conclusion, our data provided the first evidence that fisetin played a critical role in neuroprotection after TBI partly through the activation of the Nrf2-ARE pathway. PMID- 29792951 TI - An analysis of variability in genome organisation of intracellular calcium release channels across insect orders. AB - Using publicly available genomic data, combined with RT-PCR validation, we explore structural genomic variation for two major ion channels across insect classes. We have manually curated ryanodine receptor (RyR) and inositol 1,4,5 trisphosphate receptor (IP3R) ORFs and their corresponding genomic structures from 26 different insects covering major insect orders. We found that, despite high protein identity for both RyRs (>75%) and IP3Rs (~67%), the overall complexity of the gene structure varies greatly between different insect orders with the simplest genes (fewest introns) found in Diptera and the most complex in Lepidoptera. Analysis of intron conservation patterns indicated that the majority of conserved introns are found close to the 5' end of the channels and in RyR around the highly conserved mutually exclusive splice site. Of the two channels the IP3Rs appear to have a less well conserved organisation with a greater overall number of unique introns seen between insect orders. We experimentally validated two of the manually curated ORFs for IP3Rs and confirmed an atypical (3799aa) IP3R receptor in Myzus persicae, which is approximately 1000 amino acids larger than previously reported for IP3Rs. PMID- 29792956 TI - Development of photo-modified starch/kefiran/TiO2 bio-nanocomposite as an environmentally-friendly food packaging material. AB - This paper reports on an experiment in which starch/kefiran/TiO2 (SKT)-based bio nanocomposite films were developed and modified by photo-chemical reaction. In so doing, film-forming solutions were exposed to ultraviolet A (UV-A) for different times (1, 6, and 12 h). The obtained results indicated that increasing UV-A exposure time brought about an increase (~14.9%) in the tensile strength of bio nanocomposites. However, elongation at break and Young's modulus of irradiated film specimen decreased (~32%, ~12%, respectively) by increasing UV-A exposure time, and the moisture-sensitive parameters of specimen decreased using UV-A irradiation. According to the results, the functional properties of irradiated bio-nanocomposite are depended on the ratio of cross-linkages between polymer chains and the potentially produced mono and disaccharide by UV-A. PMID- 29792957 TI - High-activity production of xylanase by Pichia stipitis: Purification, characterization, kinetic evaluation and xylooligosaccharides production. AB - As an industrially important biological macromolecule, xylanase hydrolyzes xylan to produce xylooligosaccarides (XOS). XOS, with a degree of polymerization (DP) 2 to 4, are important prebiotics used as food ingredients. In this study, xylanase (5536 U/g substrate) was produced by Pichia stipitis using corncob and wheat bran mixture under solid state fermentation. Crude xylanase were purified and biochemically characterized. XOS hydrolyzed by crude and purified xylanases were quantified. Molecular weight of the purified enzyme was around 31.6 kDa on SDS PAGE. Enzyme kinetics showed Km and Vmax values of 4.52 mg/mL and 9.17 MUmol/min/mL, respectively. The optimal conditions were pH 6.0 and 50 degrees C. Xylanase was stable at pH 5-8 for 60 min by retaining 57% activity and at 50 degrees C for 80 min by retaining 65% activity. Cooper and potassium had no inhibitory effect on xylanase activity. Xylan hydrolysates produced by purified xylanase contained 92% XOS consisting of 14% xylotetroase (DP 4), 49% xylotriose (DP 3) and 29% xylobiose (DP 2). These findings indicate the potential of applying purified xylanase for industrial XOS production. PMID- 29792958 TI - Impact of cooking conditions on the properties of rice: Combined temperature and cooking time. AB - Changes in the properties of cooked rice under various cooking conditions were investigated. Waxy, low-, and high-amylose rice were subjected to treatment with different cooking temperatures (50, 70, 90 degrees C) for different cooking times (15, 30, 45 min). The results showed that cooking greatly increased the swelling behavior of waxy rice but decreased the swelling behavior and amylose leaching of low- and high-amylose rice. As the cooking temperature increased, rapidly digestible starch increased significantly for all rice products, whereas slowly digestible starch and resistant starch had a certain degree of reduction. Variation in the cooking time produced little effects on starch digestibility. Gelatinization temperature was positively correlated with temperature and time, whereas gelatinization enthalpy was negatively correlated with temperature and time. Pasting properties of all rice products decreased significantly as cooking temperature and time increased. The study showed that both cooking temperature and cooking time had significant impacts on the physicochemical properties and starch digestibility of waxy, low-, and high-amylose rice to various extents. Temperature had a more pronounced impact on the extent of change to the in vitro digestibility than did cooking time. PMID- 29792961 TI - Composite films of regenerate cellulose with chitosan and polyvinyl alcohol: Evaluation of water adsorption, mechanical and optical properties. AB - The aim of this study was to develop composite films from cellulose, chitosan and polyvinyl alcohol to obtain environmentally friendly materials. Toughness, burst strength, distance to burst and water adsorption properties were measured and analysed as a function of cellulose (3-5%), chitosan (0-1%) and polyvinyl alcohol (0-4%) contents. Polynomial models were obtained. Light-barrier properties, transparency, morphology, structural and thermal analyses were assessed. Results showed that chitosan and polyvinyl alcohol enhanced the mechanical properties of cellulose-based films. Toughness values ranged from 0.47 to 8.01 MJ/m3, burst strength values ranged from 929 to 6291 g, distance to burst ranged from 1.25 to 2.52 mm and water adsorption values ranged from 52.30 to 143.56%. Cellulose and chitosan improved the UV light protection effect of the films. However, PVA increased the transmittance meanwhile improved the film transparency. FT-IR and DSC showed an interaction between the components of the films. Results showed that it is feasible to obtain cellulose-chitosan-polyvinyl alcohol composite films with improved mechanical properties, high capacity to adsorb water, good barrier properties against UV radiations and adequate transparency value. These properties could be useful for potential packaging applications in the food industry or as a partial alternative to synthetic films. PMID- 29792959 TI - Fabrication and cytotoxicity assessment of cellulose nanofibrils using Bassia eriophora biomass. AB - Cellulose nanofibrils (CNs) are eco-friendly, biodegradable, biocompatible, renewable, cost-effective, and possess excellent mechanical properties. We fabricated CNs from Bassia eriophora biomass, and the structure and morphology were investigated by transmission electron microscopy that revealed 2-6 MUm long fibrillated structures with diameters of 15-40 nm. CNs biocompatibility was assessed using in vitro based assays, including cell viability assay, AO/EB staining, Hoechst staining, JC-1 staining, and gene expression analysis. The assessment of cellular and nuclear morphologies of human mesenchymal stem cells (hMSCs) showed that CNs do not affect cell viability and morphology. JC-1 staining results revealed that CNs do not cause mitochondrial membrane potential of hMSCs. Cell-based in vitro assays revealed that CNs are biocompatible even at high concentrations. The CNs effect on cell cycle regulated gene expression was studied that results suggested that CCND1 and CCND3 gene expression levels increased slightly, when compared with control. But CCNG1, CYCS3, and CCNC1 genes has no significant difference was observed. Overall, our results suggested that CNs can be used for tissue engineering and regenerative medicine. PMID- 29792960 TI - Hybrid chitosan-TiO2/ZnS prepared under mild conditions with visible-light driven photocatalytic activity. AB - Thin films of chitosan (CS) coated on glass substrates were used as support for the immobilization of nanostructures TiO2/ZnS via a mild chemical process followed by a hydrothermal treatment at 90 degrees C. The preparation route involved the coating of the CS film on the glass substrate followed by the deposition of a thin layer of Ti(OBu)4 precursor and immersion in a solution of Zn(O2CCH3)2 and Na2S. After a hydrothermal treatment at 90 degrees C, an even layer of TiO2 anatase decorated by ZnS nanorods was generated. Evidence of the formation of TiO2 anatase and ZnS was confirmed by XRD, Raman and XPS, and the morphology of the TiO2 layer and ZnS nanoparticles was analyzed by FE-SEM observations. The photocatalytic activity of the CS-TiO2-ZnS systems was evaluated by the degradation of a wide range of organic compounds including aromatic amines and carboxylic acids under a conventional halogen lamp. PMID- 29792962 TI - Effect of casein and inulin addition on physico-chemical characteristics of low fat camel dairy cream. AB - The effect of the addition of the camel casein fraction on some physico-chemical properties of low fat camel milk cream was studied. Oil-in-water emulsions, 25, 30, and 35 (w/w) fat, were prepared using inulin, camel skim milk, milk fat and variable percentages of casein (1, 2, and 3% w/w). The droplet size, zeta potential, surface protein concentration, viscosity and surface tension of low fat dairy creams was measured. Cream containing 2% (w/w) casein had better stability. The modifications in physico-chemical properties appeared to be driven by changes in particle size distribution caused by droplet aggregation. The cream containing 2% casein leads to a gradual decrease in droplet size, as the particle size decreased, apparent viscosity increased. When casein concentration increased, zeta-potential decreased due to combination of c terminal (negative charge) with the surface of fat particles but steric repulsion improved textural properties. Cream with 30% fat and 2% casein had the best result. PMID- 29792963 TI - Extraction, characterization and biological activity of sulfated polysaccharides from seaweed Dictyopteris divaricata. AB - Dictyopteris divaricata is a kind of important brown algae with many biological activities. It has been receiving more and more attention, yet there are rarely studies done on its polysaccharides. In this study, the optimum extraction and biological activity of seaweed polysaccharides from Dictyopteris divaricata (DDSP) were investigated. Response surface methodology (RSM), based on a three level, three-variable Box-Behnken design (BBD), was employed to obtain the best possible combinations for maximum polysaccharides yield. The optimum extraction conditions were as follows: liquid-solid ratio of 110 mL/g, extraction time of 6 h and extraction temperature of 100 degrees C. Under these conditions, the experimental yield was 3.05%, which was in close agreement with the predicted value of 3.15%. The average molecular weight of DDSP was 58.05 kDa. Gas chromatograph (GC) results showed that DDSP was composed of fucose, xylose, mannose, glucose and galactose with the corresponding molar ratio of 4.45:2.74:1.00:2.94:1.35. Biological activity showed that DDSP exhibited strong antioxidant activity in vitro and possessed the potential on stimulating immune response of RAW264.7 cells. So DDSP can be used as a natural ingredient in functional foods. PMID- 29792964 TI - A family 30 glucurono-xylanase from Bacillus subtilis LC9: Expression, characterization and its application in Chinese bread making. AB - A GH30-8 endoxylanase was identified from an environmental Bacillus subtilis isolate following growth selection on aspen wood glucuronoxylan. The putative endoxylanase was cloned for protein expression and characterization in the Gram positive protease deficient protein expression host B. subtilis WB800. The extracellular activity obtained was 55 U/mL, which was 14.5-fold higher than that obtained with the native species. The apparent molecular mass of BsXyn30 was estimated as 43 kDa by SDS-PAGE. BsXyn30 showed an optimal activity at pH 7.0 and 60 degrees C. Recombinant BsXyn30 displayed maximum activity against aspen wood xylan, followed by beechwood xylan but showed no catalytic activity on arabinose substituted xylans. Analysis of hydrolyzed products of beechwood xylan by thin layer chromatography and mass spectroscopy revealed the presence of xylooligosaccharides with a single methyl-glucuronic acid residue. BsXyn30 exhibited very low activity for hydrolysis xylotetraose and xylopentaose, but had no detectable activity against xylobiose and xylotriose. Using BsXyn30 as an additive in breadmaking, a decrease in water-holding capacity, an increase in dough expansion as well as improvements in volume and specific volume of the bread were recorded. Thus, the present study provided the basis for the application of GH30 xylanase in breadmaking. PMID- 29792965 TI - Characterization, sulfated modification and bioactivity of a novel polysaccharide from Millettia dielsiana. AB - Millettia dielsiana is a traditional herb medicine to treat rheumatic arthritis and gynecological diseases. In this study, a novel polysaccharide (MDP1) with a molecular weight of 139.54 kDa was isolated from Millettia dielsiana by DEAE-52 cellulose chromatography. Its sulfated derivative (S-MDP1) was prepared by the chlorosulfonic acid-pyridine method. Structural analysis indicated that MDP1 was a pectic polysaccharide and did not exhibit a triple helical conformation. In vitro, MDP1 and S-MDP1 had protective effect on H2O2-induced PC12 cells death. Immunological assay showed that MDP1 and S-MDP1 significantly stimulated NO production and phagocytic activity in RAW264.7 cells, and promoted lymphocyte proliferation. Anticoagulant assay indicated that S-MDP1 effectively prolonged activated partial thromboplastin time (APTT) and thrombin time (TT), but not prothrombin time (PT), and MDP1 prolonged APTT and TT weakly. These results implied that MDP1 and S-MDP1 had the potential to be used as antioxidant, immunomodulatory and anticoagulant agents. PMID- 29792966 TI - One-step fabrication of chitosan-Fe(OH)3 beads for efficient adsorption of anionic dyes. AB - In this study, we reported the one-step synthesis of chitosan-Fe(OH)3 beads without the use of acid solvent, which could be used as effective adsorbents for anionic dyes removal. The preparation process was easy and green. The as-prepared beads were characterized for structural and morphological analysis in detail using several techniques, such as Scanning Electron Microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, X-ray photoelectron spectroscopy and Thermogravimetric analysis. The content of Fe(OH)3 in chitosan-Fe(OH)3 beads was 54.64 wt%. The removal efficiencies toward anionic dyes: congo red (CR) and methyl orange (MO) by chitosan-Fe(OH)3 beads were higher than pure chitosan beads. Moreover, the incorporation of Fe(OH)3 into chitosan beads could overcome the obstacle that powdery Fe(OH)3 particles are difficult to be separated from the adsorption solutions. The maximum adsorption capacities from Langmuir model for CR and MO by chitosan-Fe(OH)3 beads were 445.32 and 314.45 mg/g, respectively. The thermodynamic data indicated that the adsorption processes were spontaneous and endothermic. In addition, chitosan-Fe(OH)3 beads also showed good reusability and the removal efficiencies for both dyes retained above 95% after five cycles. From this work, it suggests that chitosan-Fe(OH)3 beads have great potential as low-cost and effective adsorbents for the removal of anionic dyes. PMID- 29792969 TI - Impact of extended-spectrum beta-lactamases and carbapenem-resistant Gram negative infections on sepsis mortality at the emergency department: a cohort study. PMID- 29792967 TI - Validated reverse phase HPLC diode array method for the quantification of intact bevacizumab, infliximab and trastuzumab for long-term stability study. AB - The aim of the present study was to develop suitable and reliable method for quantification three of the most worldwide used therapeutic monoclonal antibodies (mAbs) -bevazizumab (BVZ), infliximab (INF) and trastuzumab (TTZ)- to be used in long-term stability studies. Reverse phase (RP) was selected by its greater sensibility and reproducibility comparing with other chromatographic modes. Then a high performance liquid chromatography with diode array detection (RP)HPLC/DAD method was checked. Since the three mAbs represent the active ingredient in the medicines in which they are formulated, the selected method was validated for each one in accordance with the International Conference on Harmonization (ICH) guidelines for pharmaceuticals for human use. Then method was validated in terms of linearity, accuracy, precision, (repeatability, intermediate precision) specificity (by forced degradation studies), robustness and system suitability. Spectral peak purity analysis strategy was used to test mAb degradations. Comparative study of the results indicated similar behavior for the three mAbs. Forced degradation studies also provided deep knowledge of these important bio macromolecules. At last the method was successfully used to quantify BVZ, INF and TTZ in long-term stability studies performed under hospital conditions of use and they showed great stability regarding quantification during the time of the study. PMID- 29792970 TI - Investigation of the efficacy of alcohol-based solutions on adenovirus serotypes 8, 19 and 37, common causes of epidemic keratoconjunctivitis, after an adenovirus outbreak in hospital. AB - BACKGROUND: Hand antiseptics are of great importance in the prevention of nosocomial infections. Due to the frequent occurrence of adenoviral epidemic keratoconjunctivitis outbreaks in the study hospital, it was necessary to investigate the efficiency of alcohol-based solutions on adenoviruses. AIM: To investigate the efficacy of alcohol-based solutions commonly found in hand antiseptics against adenovirus serotypes 8, 19 and 37. METHODS: The efficacy of ethanol, isopropanol, chlorhexidine-digluconate, n-butanol and different combinations of these antiseptics on adenovirus serotypes that typically cause epidemic keratoconjunctivitis was investigated. The effect of antiseptic substances was investigated using a quantitative suspension test technique according to EN-14476. Antiseptics were prepared as follows: 70% ethanol, 70% isopropanol, 70% ethanol+0.5% chlorhexidine-digluconate, 70% isopropanol+0.5% chlorhexidine-digluconate, 60% ethanol+10% isopropanol, 60% ethanol+10% isopropanol+0.5% chlorhexidine-digluconate and 60% ethanol+10% isopropanol+1% n butanol. The effect of antiseptics was evaluated at 30, 60 and 120 s. FINDINGS: The highest reduction in virus titre was detected with 60% ethanol+10% isopropanol+1% n-butanol. This caused a reduction of 2.5log10, 3 log10 and 2.5log10 in adenovirus serotypes 8, 19 and 37, respectively. The lowest reduction in virus titre was detected with 70% ethanol+0.5% chlorhexidine-digluconate and 70% isopropanol+0.5% chlorhexidine-digluconate. These combinations caused a reduction of 1.62log10 in adenovirus serotypes 19 and 37. All antiseptics showed efficacy levels below 4log10 which is regarded as the efficiency limit by EN 14476. CONCLUSION: The alcohol-based solutions tested in this study were not found to be sufficiently effective against adenovirus serotypes. Further studies to investigate the efficiency of different alcohol-based solutions are required. PMID- 29792968 TI - Applicability of endochitinase of Flavobacterium johnsoniae with transglycosylation activity in generating long-chain chitooligosaccharides. AB - Chitin and its derivatives are used for a variety of applications. Flavobacterium johnsoniae UW101 is an aerobic Gram-negative bacterium. Genome analysis of F. johnsoniae UW101 revealed the presence of 10 glycoside hydrolases (GHs) that may degrade or modify chitin. The gene encoding chitinase B (FjchiB), which encodes a single catalytic GH18 domain has been cloned and heterologously expressed in Escherichia coli. FjChiB was optimally active in 50 mM sodium citrate buffer (pH 6.0) at 40 degrees C. FjChiB was salt-tolerant and catalytically versatile, with substrate specificity towards 75% DDA (degree of de-acetylation) chitosan, followed by colloidal chitin. Chitotetraose (DP4) was the shortest of the oligomeric substrates used by FjChiB. The Km and Vmax values of FjChiB for colloidal chitin were 49.38 mg/ml and 11.2 nanokat mg-1, respectively. The overall catalytic efficiency (kcat/Km) of FjChiB was 1.40 * 103 mg-1 ml s-1. FjChiB exhibited transglycosylation (TG) with chitopentaose (DP5) and chitohexaose (DP6) substrates. The TG by FjChiB was fine-tuned by introducing a tryptophan (G106W) and asparagine (D148N) in the highly conserved catalytic groove and catalytic center, respectively. Hydrolytic products profile and homology modelling indicated that FjChiB is an endochitinase that holds promise for the conversion of chitin into useful products through both TG and/or hydrolysis. PMID- 29792971 TI - Impact of active surveillance and infection control measures on carbapenem resistant Gram-negative bacterial colonization and infections in intensive care. AB - BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CRGNB) infections constitute a global threat for critically ill patients and the outcome of their hospitalization. Early identification of CRGNB through rectal surveillance cultures and routine infection control measures including contact precautions, use of appropriate disinfectants, staff education on cleaning, and hand hygiene may reduce the dissemination of CRGNB. AIM: To assess the impact of enhanced infection control measures on CRGNB infections in a nine-bed polyvalent intensive care unit in a tertiary level hospital in an endemic area. METHODS: A quasi experimental study, which included patients with CRGNB infection retrospectively for six months and those participating in an active surveillance programme prospectively for the subsequent 22 months. Active surveillance programme (weekly rectal swabs) was implemented including two sub-periods with infection control measures and enhanced infection control measures. CRGNB incidence, prevalence, colonization pressure, infections and compliance with infection control measures and enhanced infection control measures were recorded. Analysis was performed through time-series and interrupted time-series. FINDINGS: During the active surveillance programme, enhanced infection control measures led to a steeper downwards trend in incidence, prevalence, and colonization pressure for CRGNB compared to the infection control measures sub-period. The linear trend was for carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) infections to decrease from 19.6 to 8.1 infections per 1000 bed-days (IBD) (P = 0.001) and from 5.1 to 1.79 IBD (P = 0.043), respectively. By contrast, carbapenem-resistant Acinetobacter baumannii infections increased from 5.2 to 15.3 IBD (P = 0.001). CONCLUSION: Enhanced infection control measures including enhanced hand hygiene, active surveillance combined with contact precautions, education, audits and feedback policies and interventions could reduce CRKP and CRPA in endemic areas. PMID- 29792972 TI - Association Between Early Confirmatory Testing and the Adoption of Active Surveillance for Men With Favorable-risk Prostate Cancer. AB - OBJECTIVE: To examine the relationship between the use and results of early confirmatory testing and persistence on active surveillance (AS). METHODS: We identified all men in the Michigan Urological Surgery Improvement Collaborative registry diagnosed with favorable-risk prostate cancer from June 2016 to June 2017. We next examined trends in the use of early confirmatory test(s), defined as repeat biopsy, prostate magnetic resonance imaging, or molecular classifiers obtained within 6 months of the initial cancer diagnosis, in patients with favorable-risk prostate cancer. We then compared the proportion of men remaining on AS 6 months after diagnosis according to reassuring vs nonreassuring results, also stratifying by age and Gleason score. RESULTS: Among 2529 patients, 32.7% underwent early confirmatory testing within 6 months of diagnosis. Its use increased from 25.4% in the second quarter of 2016 to 34.9% in the second quarter of 2017 (P = .025). Molecular classifiers were most frequently used (55%), followed by magnetic resonance imaging (34%) and repeat biopsy (11%). Sixty-four percent (n = 523) had a reassuring result. Rates of AS were higher for patients with early reassuring results; 82% remained on AS (n = 427) compared to 52% (n = 157) of those with nonreassuring results and 51% (n = 873) with no early confirmatory testing (P <.001). CONCLUSION: Rates of AS are higher among men with early reassuring results, supporting the clinical utility of these tests. Nonetheless, high rates of AS among patients with nonreassuring results underscore the complexity of shared decision-making in this setting. PMID- 29792973 TI - Re: Jianrong Huang et al: The Application of Suctioning Flexible Ureteroscopy with Intelligent Pressure Control in Treating Upper Urinary Tract Calculi on Patients With a Solitary Kidney. UROLOGY 111: 44-47, 2018. PMID- 29792974 TI - Patient Compliance With Maintenance Intravesical Therapy for Nonmuscle Invasive Bladder Cancer. AB - OBJECTIVE: To assess patient adherence to intravesical instillation therapy for nonmuscle invasive urothelial carcinoma outside of clinical trials. MATERIALS AND METHODS: We reviewed the records of patients from 2000 to 2013 who received intravesical therapy for nonmuscle invasive urothelial carcinoma. Patients with evidence of tumor recurrence or progression were excluded. We performed univariable and multivariable regression analyses to predict adherence to intravesical therapy. RESULTS: A total of 729 patients started 861 induction cycles, 63% with bacillus Calmette-Guerin (BCG) and 37% with mitomycin C (MMC). The rate of completion of 6 weeks induction therapy with BCG and MMC was similar (86% and 87%, respectively). Within the BCG cohort, 161 (35%) patients commenced the Southwest Oncology Group (SWOG) maintenance protocol after induction and 16 (10%) completed all 21 treatments. A monthly protocol for BCG was started by 87 patients (19%) and 48 (55%) completed all 9 treatments. MMC therapy was started in 270 patients, 97 of whom (36%) commenced monthly maintenance treatment, and 46 (47%) completed treatments. Median number of instillations was 7 for patients undergoing monthly maintenance therapy (MMC or BCG) and 9 for patients allocated to 3 years BCG. On multivariable analysis, recurrence after prior treatment of urothelial carcinoma was predictive of patients' adherence to treatment. CONCLUSION: Compliance with intravesical therapy is low in clinical practice, notably for longer treatment schedules. PMID- 29792975 TI - Bladder Agenesis and Associated Pelvic Arterial Anomaly in 2 Female Pediatric Patients. AB - Bladder agenesis is an extremely rare congenital anomaly of the genitourinary tract. Two female patients with known diagnoses of bladder agenesis presented for prerenal transplant evaluation and neobladder creation. Similar unique pelvic arterial malformations were identified through preoperative imaging and intraoperative examination. With these similar findings, it could be proposed that such anatomical variants are products of the same insult or involve a causal relationship, with vascular aberrancies potentially provoking pelvic organ maldevelopment. We advocate detailed mapping of the pelvic arterial tree preoperatively in bladder agenesis cases to prevent arterial injury and to safely delineate anatomy for appropriate transplant placement. PMID- 29792977 TI - Hydromorphone Conversion Dilemma: A Millennial Problem. PMID- 29792976 TI - Simultaneous Bilateral Ureteral Calculi: A New Paradigm for Management. AB - OBJECTIVE: To define the need for emergent intervention between patients with simultaneous bilateral ureteral calculi (SBUC) compared to unilateral ureteral calculi (UUC). Patients with SBUC represent a potential urological emergency due to possible anuria or electrolyte imbalance. While conventional practice mandates immediate intervention in these patients, little data exist to define the rate of these events. METHODS: Records of all patients with ureteral stones treated ureteroscopically over an 11-year period were reviewed to identify those with SBUC. Patient presenting characteristics, time from diagnosis to intervention, and postoperative outcomes were noted. To determine the need for emergent intervention, we compared metabolic and infectious parameters between SBUC patients and age- and sex-matched patients with UUC. RESULTS: A total of 3800 patients presented with ureteral calculi including 42 (1.1%) with SBUC. Two thirds of patients with SBUC had an established diagnosis of nephrolithiasis. Among the 42 patients with SBUC, 11 (26.2%) were considered emergent due to metabolic (5 of 11, 45.5%), infectious (1 of 11, 9.1%), or both metabolic and infectious indications (5 of 11, 45.5%). No patients required acute dialysis before surgical intervention. Compared to patients with UUC, those with SBUC were significantly more likely to require emergent management (P = .03, odds ratio 2.3). Univariate and multivariate analyses showed this to be due to anuria (P = .001) and acidosis (P = .003). CONCLUSION: SBUC is an uncommon condition and, in this series, only the minority of patients presented emergently. Therefore, patients with SBUC can often be managed electively if counseled on clinical signs warranting emergent medical attention. Appropriately selected patients have excellent outcomes following single stage bilateral ureteroscopy. PMID- 29792978 TI - Authors' Response. PMID- 29792979 TI - Immune Checkpoint Inhibitor Toxicity Review for the Palliative Care Clinician. AB - Immune checkpoint inhibitors (ICIs) have opened an exciting chapter in the treatment of patients with advanced cancer. For the palliative care clinician, however, ICIs present several new challenges, including new ways to define treatment success, as well as treatment-related toxicities that differ in nature and timing from traditional chemotherapy. In this article, we review the mechanism of action of ICIs, as well as selected published data supporting the efficacy of ICIs in patients with advanced cancer. In addition, we summarize existing data of ICI toxicity prevalence, patterns of severity, and timing of onset. Finally, we briefly review key principles from published guidelines on the management of ICI toxicities. PMID- 29792980 TI - Language Used by Health Care Professionals to Describe Dying at an Acute Care Hospital. AB - CONTEXT: Clinicians often rely on documentation to relay information, and this remains the mainstay of interprofessional communication regarding patient care. However, there has been scant research focused on clinicians' documentation of dying in hospital and how this is communicated to other team members in patient charting. OBJECTIVES: To understand the language used to describe the deterioration and death of patients in an acute academic tertiary care center and to identify whether patient diagnoses or palliative care (PC) involvement was associated with clearer descriptions of this process. METHODS: We conducted a retrospective chart review of the final admission of 150 patients who died on an inpatient internal medicine unit. Conventional and summative content analysis was performed of the language used to describe, either directly or indirectly, that the patient's death was imminent. RESULTS: Of the 150 deaths, the median age was 79.5 (range 22-101), 58% were males, and 69% spoke English. A total of 45% of deaths were from cancer, and 66% occurred with prior PC team involvement. There was no documentation of the dying process in 18 (12%) charts. In the remainder, clinicians' documentation of imminent death fell into three categories: 1) identification of the current state using specific labels; for example, dying (24.7%) or end of life (15.3%), or less specific language, unwell or doing poorly (6.0%); 2) predicting the future state using specific or more vague predictions; for example, hours to days (7.3%) or poor or guarded prognosis (26.0%); and 3) using care provided to the patient to imply patient status; for example, PC (49.3%) or comfort care (28.7%). PC involvement, but not a malignant diagnosis, was associated with more frequent use of specific language to describe the current state (P = 0.004) or future state (P = 0.02). CONCLUSION: Death and dying in hospital is inadequately documented and often described using unclear and vague language. PC involvement is associated with clearer language to describe this process. PMID- 29792984 TI - 'Convergence' created psychoneuroimmunology, and is needed again to secure the future of the field. PMID- 29792983 TI - Impact of genetic influence on serum total- and free 25-hydroxyvitamin-D in humans. AB - Serum 25-hydroxyvitamin D /25OHD/ levels in humans are determined primarily by environmental factors such as UV-B radiation and diet, including vitamin D intake. Although some genetic determinants of 25OHD levels have been shown, the magnitude of this association has not yet been clarified. The present study evaluates the genetic contribution to total- /t-25OHD/ and free-25OHD /f-25OHD/ in a representative sample of the Hungarian population (n = 462). The study was performed at the end of winter to minimize the effect of sunlight, which is a major determinant of serum vitamin D levels. Single nucleotide polymorphisms (SNPs) of five genes playing major roles in vitamin D metabolism were investigated (NADSYN1, DHCR7, GC, CYP2R1 and CYP24A1). The selected SNPs account for 13.1% of the variance of t-25OHD levels. More than half of the genetic effect on t-25OHD levels was explained by two polymorphisms (rs7935125 in NADSYN1 and rs2762941 in CYP24A1), which had not previously been investigated with respect to vitamin D metabolism. No SNPs exhibited association with f-25OHD levels. Unexpectedly, SNPs that showed univariate associations with vitamin D binding protein (DBP) levels were not associated with f-25OHD levels questioning the biological significance of these polymorphisms. The present study shows that t 25OHD levels are significantly influenced by genetic factors, however, the clinical significance of this observation remains to be defined, as variation in f-25OHD levels are marginally explained by genetic effects. PMID- 29792982 TI - Portuguese children dietary exposure to multiple mycotoxins - An overview of risk assessment under MYCOMIX project. AB - Mycotoxins are secondary fungi metabolites that induce acute and chronic toxic effects in humans and animals. Simultaneous contamination of cereal-based products by multiple mycotoxins has been increasingly reported, including in food products usually consumed by children. Although some previous authors assessed the health risk of children exposed to multiple mycotoxins, scarce data are available on the risk associated with the ingestion of multiple mycotoxins through different food products. MYCOMIX, a national funded project, intended to contribute to fill this gap. The present study aimed to overview the risk assessment of multiple mycotoxins performed under MYCOMIX, assessing for the first time, the risk associated with the exposure to 13 mycotoxins in breakfast cereals, infant cereals and biscuits consumed by children from Lisbon region, Portugal. Results on mycotoxins occurrence showed that 94% of samples were contaminated with at least one mycotoxin, although at levels below the legislated limits. Co-contamination was observed in 75% of the analysed samples. Estimated aflatoxins exposure suggested a potential adverse health effect for percentiles of intake above or equal to P50. The obtained results suggested that future research actions should be set in motion in order to protect children health. PMID- 29792981 TI - Probabilistic non-carcinogenic and carcinogenic risk assessments (Monte Carlo simulation method) of the measured acrylamide content in Tah-dig using QuEChERS extraction and UHPLC-MS/MS. AB - A modified "Quick, Easy, Cheap, Effective, Rugged, and Safe" QuEChERS in combination with Ultra-High Performance Liquid Chromatography/tandem mass spectrometry (UHPLC-MS/MS) method was optimized for the determination of acrylamide content in different types of tah-dig (rice, bread, and potato). Also, the non-carcinogenic and carcinogenic risks (target hazard quotient (THQ) and incremental lifetime cancer risk (ILCR)) due to ingestion of acrylamide via tah dig in the adults and children were assessed by Monte Carlo simulation (MCS) method. The recoveries of acrylamide at five concentration levels (n = 3) ranged from 83.82% to 106.41%. The repeatability of the proposed method was demonstrated with RSD% in the range of 11.3-20%. In addition, the limits of detection and quantification were reported as 5 ngg-1 and 15 ngg-1, respectively. The mean levels of the acrylamide contents in rice tah-dig, bread tah-dig, and potato tah dig were measured as 24.65 ngg-1, 39.48 ngg-1, and 714.11 ngg-1, respectively. The highest acrylamide content was determined in potato tah-dig (2100 ngg-1) and the lowest acrylamide in rice tah-dig (<=LOQ). Based on the conducted risk assessment, the P (95%) of cumulative probability in the MCS method, the lowest and highest THQ was observed in the adults (ingestion bread tah-dig: 1.29E-2), and children (ingestion potato tah-dig: 1.90E+00), respectively. Additionally, the lowest and highest ILCR were reported in adults (ingestion bread tah-dig: 1.29E-5) and children (ingestion potato tah-dig: 7.49E-3), respectively. The rank order of type tah-dig based on THQ and ILCR for all groups of consumers was potato tah-dig > rice tah-dig > bread tah-dig. There is a considerable non carcinogenic risk for the children due to ingestion potato tah-dig (THQ > 1). Additionally, the significant carcinogenic risk for the Iranian adults and children due to consumption of rice, bread, and potato tah-dig (ILCR > 1.00E-5) was observed. PMID- 29792985 TI - Novel excipients - Regulatory challenges and perspectives - The EU insight. AB - Novel excipients are indispensable in development of modern, advanced drug delivery systems and biotechnology-derived drugs. Although numerous novel excipients are developed for pharmaceutical use, they are not frequently seen in medicinal products due to the strict regulatory requirements and perception that their use makes new product evaluation more complex with risk of delays in the approval process. Regulators regard novel excipients as new substances and whenever new excipient is used in a formulation it must be subjected to full evaluation, similarly to the one required for new active substance. Consequently, the amount of information required in support of the regulatory approval (i.e. marketing authorization) is much more complex and comprehensive than for established excipients. This short review provides an insight into the use of novel excipients in medicinal products approved in the European Union. In addition, barriers and challenges in development of novel excipients are being discussed as well as means to overcome those barriers. PMID- 29792986 TI - Model-based NIR spectroscopy implementation for in-line assay monitoring during a pharmaceutical suspension manufacturing process. AB - The implementation of Process Analytical Technology (PAT) instruments is generally achieved stochastically. Sub-optimal PAT locations could introduce variation in the measurements which is not related to the analyte of interest. For this reason, rational approaches should be considered to establish an optimal sensor placement where relevant measurements are possible and the impact of disturbances is minimized. The aim of this paper is to demonstrate how mechanistic modelling can support appropriate sensor implementation by means of a case study. A PAT method was developed for a bottle filling process of a pharmaceutical formulation with the goal of increasing the yield of the process by gaining process understanding and redefining the endpoint of the process. To ensure proper measurements, an advanced measuring interfacing was assembled. The design of this device was rationalized with the help of a model-based approach using three-dimensional Computational Fluid Dynamics modeling. This allows to maximize the performance of the PAT method and exploit its full benefits. PMID- 29792987 TI - The rheological and textural characterization of Soluplus(r)/Vitamin E composites. AB - Soluplus(r) is a graft amphiphilic copolymer that is frequently used as an excipient in solid dosage forms as a dissolution and a solubility enhancer. We discovered that Soluplus(r) can be dissolved in vitamin E. The result is a tacky and highly adhesive material. Our research objective was to evaluate the rheological, adhesive, and textural properties of the Soluplus(r)/Vitamin E composites. In this study, Soluplus(r) was dissolved under heat in vitamin E at increasing concentrations from 0 to 40% (by weight). The flow behavior of the Soluplus(r)/Vitamin E composites was determined by applying shear stress using an advanced AR2000 rheometer. Under the linear viscoelastic region (LVR), the rheological properties of the blends such as dynamic viscosity (eta'), storage modulus (G'), loss modulus (G"), and the phase angle tangent (tan delta) were measured. Hardness, adhesiveness, and cohesiveness of the blends were also measured with a TA.XT plus texture analyzer. Rheological analysis showed that the viscosity of the Soluplus(r)/Vitamin E composites increased with an increase in Soluplus(r) concentration but decreased as the temperature increased from 20 to 90 degrees C. The adhesiveness of the blends also significantly increased with an increase in Soluplus(r) concentration. The results from this study indicated that Soluplus(r)/Vitamin E composites have the potential to be exploited in applications where the use of highly adhesive material is desirable. PMID- 29792988 TI - Towards quantitative prediction of the performance of dry powder inhalers by multi-scale simulations and experiments. AB - This work demonstrates the use of multi-scale simulations coupled with experiments to build a quantitative prediction tool for the performance of adhesive mixtures in a dry powder inhaler (DPI). Using discrete element model (DEM), the behaviour of fine-carrier particle assemblies upon different mechanisms encountered during dose entrainment and dispersion can be described at the individual particle level. Combining these results with computational fluid dynamics (CFD) simulations, the complete dosing event from a DPI can be captured and key performance measures can be extracted. A concept of apparent surface energy, ASE, was introduced to overcome challenges associated with the complex particle properties, e.g. irregular particle shapes and surface roughness. This approach correctly predicts trends observed experimentally regarding API adhesivity, flow rate and device geometry. By incorporating the effects of drug load, critical adhesion and surface energy distributions to the simulation tool, the fine particle fraction could be predicted with good agreement to experiments for two different formulations in two different devices at two flow rates. It is concluded that multi-scale simulations provide a useful tool to support device and formulation development, as well as to gain further insight into the physical mechanisms governing dispersion from DPIs. PMID- 29792989 TI - Novel genotypes and multilocus genotypes of Enterocytozoon bieneusi in pigs in northwestern China: A public health concern. AB - Enterocytozoon bieneusi, the most important and common microsporidian species, inhabits in most animals and humans causing diarrhea and systemic diseases. The objectives of the present study were to examine the prevalence and genetic variability of E. bieneusi in pigs in Shaanxi province, northwestern China. A total of 560 pig faecal samples were collected from five different farms in Shaanxi province and molecularly characterized using multilocus genotyping (MLST) technology. High E. bieneusi infection rate (78.9%) was observed in these samples. 12 known and 22 possible novel ITS genotypes were identified, with the novel SZZD1 as the predominant genotype distributed in all age groups and pig farms. 32 (including 11 known and 21 novel ones) of them belong to the zoonotic group 1. MLST analysis showed that 109 ITS positive samples formed 87 distinct multilocus genotypes (MLGs). An incomplete linkage disequilibrium (LD) and clonal genetic structure of E. bieneusi were found in pigs in Shaanxi province. These findings indicated the complex population structures of E. bieneusi in pigs in Shaanxi province and provided baseline data for better understanding of the epidemiological status of E. bieneusi in this province. PMID- 29792991 TI - Codon adaptation biases among sylvatic and urban genotypes of Dengue virus type 2. AB - Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle. PMID- 29792990 TI - Identification of group A rotaviruses from Zambian fruit bats provides evidence for long-distance dispersal events in Africa. AB - Group A rotavirus (RVA) is a major cause of diarrhea in children worldwide. Although RVA infects many animals, little is known about RVA in bats. The present study investigated the genetic diversity of RVA in Zambian bats. We identified RVA from two straw-colored fruit bats (Eidolon helvum) and an Egyptian fruit bat (Rousettus aegyptiacus), and analyzed the genome sequences of these strains. Genome segments of the RVA strains from Zambian E. helvum showed 97%-99% nucleotide sequence identity with those of other RVA strains from E. helvum in Cameroon, which is 2800 km from the sampling locations. These findings suggest that migratory straw-colored fruit bat species, distributed across sub-Saharan Africa, have the potential to disseminate RVA across long distances. By contrast, the RVA strain from Zambian R. aegyptiacus carried highly divergent NSP2 and NSP4 genes, leading us to propose novel genotypes N21 and E27, respectively. Notably, this RVA strain also shared the same genotype for VP6 and NSP3 with the RVA strains from Zambian E. helvum, suggesting interspecies transmission and genetic reassortment may have occurred between these two bat species in the past. Our study has important implications for RVA dispersal in bat populations, and expands our knowledge of the ecology, diversity and evolutionary relationships of RVA. PMID- 29792992 TI - Frailty status as a predictor of 3-month cognitive and functional recovery following spinal surgery: a prospective pilot study. AB - BACKGROUND CONTEXT: As increasing numbers of elderly Americans undergo spinal surgery, it is important to identify which patients are at highest risk for poor cognitive and functional recovery. Frailty is a geriatric syndrome that has been closely linked to poor outcomes, and short-form screening may be a helpful tool for preoperative identification of at-risk patients. PURPOSE: This study aimed to conduct a pilot study on the usefulness of a short-form screening tool to identify elderly patients at increased risk for prolonged cognitive and functional recovery following elective spine surgery. STUDY DESIGN/SETTING: This is a prospective, comparative cohort study. PATIENT SAMPLE: The sample comprised 100 patients over age 65 who underwent elective spinal surgery (cervical or lumbar) at a single, large academic medical center from 2013 to 2014. OUTCOME MEASURES: Fatigue, Resistance, Ambulation, Illnesses, Loss of Weight (FRAIL) scale, Postoperative Quality of Recovery Scale (PQRS), and instrumental activities of daily living (IADL) scores were the outcome measures. METHODS: Included patients were assessed with the FRAIL scale and stratified as robust, pre-frail, or frail. The PQRS and IADL scores were also obtained. Patients were re-examined at 1 day, 3 days, 1 month, and 3 months after surgery for cognitive recovery at 3 months, and secondarily, functional recovery at 3 months. RESULTS: At 3 months, only 50% of frail patients had recovered to their cognitive baseline compared with 60.7% of pre-frail and 69.2% of robust patients (trend). At 3 months, 66.7% of frail patients had recovered to their functional baseline compared with 57% of pre-frail and 76.9% of robust patients (trend). Using multivariate regression modeling, at 3 months, frail patients were less likely to have recovered to their cognitive baseline compared with pre-frail and robust patients (odds ratio 0.39, confidence interval 0.131-1.161). CONCLUSIONS: This pilot study demonstrates a trend toward poorer cognitive recovery 3 months following elective spinal surgery for frail patients. Frailty screening can help preoperatively identify patients who may experience protracted cognitive and functional recovery. PMID- 29792993 TI - Responsiveness of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire in lumbar surgery and its threshold for indicating clinically important differences. AB - BACKGROUND CONTEXT: Introduced in 2007, the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) has been widely used, but its psychometric properties have not been well studied. PURPOSE: The objective of this study was to assess the responsiveness of the JOABPEQ in lumbar surgery and its threshold for indicating clinically important differences. STUDY DESIGN: This is a prospective study. PATIENT SAMPLE: Two hundred three consecutive patients underwent lumbar surgeries between July 2013 and November 2015 in a single hospital. Of the 203 patients, 181 patients who completed 1 year of follow-up were included. OUTCOME MEASURES: Before and after surgery, the patients were asked to complete the questionnaire, including JOABPEQ, the 8-Item Short Form Health Survey (SF-8), and EuroQol-5D (EQ-5D). The participants were divided into five anchoring groups, ranging from "much better" to "much worse," according to reports from both physicians and patients. MATERIALS AND METHODS: The responsiveness of measures was compared among five domains of the JOABPEQ ("low back pain," "walking ability," "lumbar function," "social function," and "mental health"), two domains of the SF-8 (the physical component summary [PCS] and the mental component summary [MCS]), and the EQ-5D. The responsiveness was assessed by the paired t test, the effect size, and the standardized response mean. The Spearman rank correlation coefficient and the receiver operating characteristic (ROC) curve were assessed using the five anchoring groups as external criteria. The clinically important differences, based on the ROC curve, were assessed. RESULTS: Walking ability was most responsive, followed by low back pain and the PCS. The MCS was least responsive, followed by mental health and lumbar function. Social function and the EQ-5D had intermediate-level responsiveness. The substantial clinically important differences occurred at 20 points for low back pain and lumbar function, 23 points for walking ability, 14 points for social function, and 8 points for mental health. CONCLUSIONS: The JOABPEQ domains are responsive measures in patients who undergo lumbar surgery. For physical function, the threshold for substantial clinically important differences was approximately 20 points for the JOABPEQ. PMID- 29792994 TI - Lumbar spinal stenosis: comparison of surgical practice variation and clinical outcome in three national spine registries. AB - BACKGROUND CONTEXT: Decompression surgery for lumbar spinal stenosis (LSS) is the most common spinal procedure in the elderly. To avoid persisting low back pain, adding arthrodesis has been recommended, especially if there is a coexisting degenerative spondylolisthesis. However, this strategy remains controversial, resulting in practice-based variation. PURPOSE: The present study aimed to evaluate in a pragmatic study if surgical selection criteria and variation in use of arthrodesis in three Scandinavian countries can be linked to variation in treatment effectiveness. STUDY DESIGN: This is an observational study based on a combined cohort from the national spine registries of Norway, Sweden, and Denmark. PATIENT SAMPLE: Patients aged 50 and older operated during 2011-2013 for LSS were included. OUTCOME MEASURES: Patient-Reported Outcome Measures (PROMs): Oswestry Disability Index (ODI) (primary outcome), Numeric Rating Scale (NRS) for leg pain and back pain, and health-related quality of life (Euro-Qol-5D) were reported. Analysis included case-mix adjustment. In addition, we report differences in hospital stay. METHODS: Analyses of baseline data were done by analysis of variance (ANOVA), chi-square, or logistic regression tests. The comparisons of the mean changes of PROMs at 1-year follow-up between the countries were done by ANOVA (crude) and analysis of covariance (case-mix adjustment). RESULTS: Out of 14,223 included patients, 10,890 (77%) responded at 1-year follow-up. Apart from fewer smokers in Sweden and higher comorbidity rate in Norway, baseline characteristics were similar. The rate of additional fusion surgery (patients without or with spondylolisthesis) was 11% (4%, 47%) in Norway, 21% (9%, 56%) in Sweden, and 28% (15%, 88%) in Denmark. At 1-year follow-up, the mean improvement for ODI (95% confidence interval) was 18 (17-18) in Norway, 17 (17-18) in Sweden, and 18 (17-19) in Denmark. Patients operated with arthrodesis had prolonged hospital stay. CONCLUSIONS: Real-life data from three national spine registers showed similar indications for decompression surgery but significant differences in the use of concomitant arthrodesis in Scandinavia. Additional arthrodesis was not associated with better treatment effectiveness. PMID- 29792995 TI - Lumbar discectomy is associated with higher rates of lumbar fusion. AB - BACKGROUND CONTEXT: Lumbar disc herniation affects more than 3 million people in the United States every year, and the rate of operation continually increases, particularly in patients 60 years or older (Taylor et al., 1994; Jordan et al., 2011). Surgical discectomy is a common treatment for lumbar disc herniation (Taylor et al., 1994; Atlas et al., 1996). One concern for this method is the risk of undergoing additional surgeries (Jordan et al., 2011; Osterman et al., 2003; Lebow et al., 2011). There are very limited population-level studies that examine the rate of lumbar fusion after lumbar discectomy. Additionally, there is no study that examines the risk of undergoing lumbar fusion in patients who have undergone lumbar discectomies compared with the risk of lumbar fusion in the general population with no previous lumbar discectomy. PURPOSE: The present study aimed to calculate a more definitive rate of lumbar fusion after a lumbar discectomy procedure using a population-size study of more than 200,000 patients in the Truven Healthcare Analytics Marketscan Research Database who underwent discectomies. Additionally, the study aimed to compare the rate of lumbar fusion in patients who have undergone a lumbar discectomy to the rate of lumbar fusion in patients with no prior lumbar discectomy procedure. STUDY DESIGN/SETTING: This is a retrospective cohort study. PATIENT SAMPLE: The patients from both parts of the present study were extracted from the Truven Healthcare Analytics Marketscan Research Database. Ten-year fusion after discectomy rates: 223,291 patients who underwent discectomies from the years 2003 to 2015. Fusion rate comparison: 489,975 patients with a previous lumbar ICD-9 (International Classification of Diseases, Ninth Revision) diagnosis code who have also been enrolled in the database for at least 10 years. OUTCOME MEASURES: Ten-year fusion after discectomy rates: The proportion of patients who received a lumbar fusion up to 10 years after a lumbar discectomy. Fusion rate comparison: The proportion of patients who received a lumbar fusion after a lumbar discectomy compared with the proportion of patients who received a lumbar fusion with no previous lumbar discectomy. METHODS: Ten-year fusion after discectomy rates: The patients who had undergone discectomies were filtered in the Marketscan database via Current Procedural Terminology (CPT) codes specific for lumbar discectomy (63030, 63035). Patients who had a lumbar fusion before or concurrently with these indexed lumbar discectomy dates were removed from the index group. The group was then followed up every year up to 10 years after the initial indexed lumbar discectomy dates for reoperation involving a lumbar spinal fusion according to the lumbar fusion CPT codes (22533, 22558, 22612, 22630, 22632, 22633, 22634, 22534, 22585, 22614). Fusion rate comparison: Study population only included patients who had a previous lumbar ICD-9 diagnosis in the Marketscan database (7242, 72210, 72251, 72252, 72273, 72293, 7213, 72142, 72283, 72293, 7243, 72402, 72403, 7244, 7245, 7249). The patients were then separated into two arms: one with patients who had undergone lumbar discectomy after initial lumbar diagnosis and another with patients who had not undergone a lumbar discectomy procedure. Pearson chi-square test was used to assess significance when comparing the proportion of patients who receive lumbar fusion after lumbar discectomy with the proportion of patients who receive lumbar fusion without a prior lumbar discectomy in the general ICD-9 lumbar diagnosis population. RESULTS: For the 10-year trend of lumbar fusion rates after lumbar discectomy, the rate of fusion ranged from 1.69% (1-year time frame after discectomy) to 8.50% (10-year time frame after discectomy). When comparing the two cohorts in the second part of the present study, the fusion rates were 12.50% for the discectomy group and 4.19% for the non-discectomy group. The Pearson chi-square test reported a statistically significant difference between the fusion rates of the two groups (p<.0001, alpha=.05). We found that people who had a lumbar discectomy procedure were 2.97 (95% confidence interval [2.86, 3.10]) times more likely to undergo a lumbar fusion than those who with a lumbar diagnosis but had not undergone a lumbar discectomy in the past. CONCLUSIONS: Our study is the largest population study that explores the rate of lumbar fusion after an initial lumbar discectomy. To our knowledge, it is the first study that concludes that an initial lumbar discectomy is statistically associated with an increased likelihood of a patient undergoing a lumbar fusion in the future. We observed that patients who had previously undergone a lumbar discectomy were roughly three times more likely to undergo a lumbar fusion procedure than a patient with a lumbar diagnosis, but had not undergone a lumbar discectomy. Although not calculated, it stands to reason the difference would be even greater when comparing the discectomy population with a population without lumbar diagnoses. This finding can be an important supplement for the physician patient discussion regarding expectations and potential for reoperation. PMID- 29792996 TI - Cervical bracing practices after degenerative cervical surgery: a survey of Cervical Spine Research Society members. PMID- 29792997 TI - Risk factors for low back pain and sciatica: an umbrella review. AB - BACKGROUND: Low back pain (LBP) is a highly prevalent condition and it is associated with significant disability and work absenteeism worldwide. A variety of environmental and individual characteristics have been reported to increase the risk of LBP. To our knowledge, there has been no previous attempt to summarize the evidence from existing systematic reviews of risk factors for LBP or sciatica. PURPOSE: To provide an overview of risk factors for LBP, we completed an umbrella review of the evidence from existing systematic reviews. STUDY DESIGN: An umbrella review was carried out. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, PubMed PsychINFO, and CINAHL databases. To focus on the most recent evidence, we only included systematic reviews published in the last 5 years (2011-2016) examining any risk factor for LBP or sciatica. Only systematic reviews of cohort studies enrolling participants without LBP and sciatica at baseline were included. The methodological quality of the reviews was assessed independently by two review authors, using the Assessment of Multiple Systematic Reviews tool. RESULTS: We included 15 systematic reviews containing 134 cohort studies. Four systematic reviews were of high methodological quality and 11 were of moderate quality. Of the 54 risk factors investigated, 38 risk factors were significantly associated with increased risk of LBP or sciatica in at least one systematic review and the odds ratios ranged from 1.26 to 13.00. Adverse risk factors included characteristics of the individual (eg, older age), poor general health (eg, smoking), physical stress on spine (eg, vibration), and psychological stress (eg, depression). CONCLUSION: Poor general health, physical and psychological stress, and characteristics of the person increase risk for a future episode of LBP or sciatica. PMID- 29792998 TI - BMI and gender increase risk of sacral fractures after multilevel instrumented spinal fusion compared with bone mineral density and pelvic parameters. AB - BACKGROUND CONTEXT: Sacral fractures are a rare but potentially devastating complication. Long-fusion constructs, including the sacrum, that do not extend to the pelvis may result in sacral fractures. Besides established risk factors including gender, age, and number of levels fused, body mass index (BMI), pelvic parameters, and bone mineral density (BMD) have also been proposed as potential risk factors for postoperative sacral fractures. The literature supporting this, however, is limited. PURPOSE: The aim of the present study was to assess whether preoperative pelvic parameters, BMI, or BMD of patients with sacral fracture are different compared with age, gender, and fusion level-matched non-fracture controls. STUDY DESIGN/SETTING: This is a case-control study. PATIENT SAMPLE: Patients undergoing posterior instrumented fusion at a single academic institution between 2002 and 2016 were included in the study. OUTCOME MEASURES: The outcome measure was occurrence of a postoperative sacral fracture. METHODS: Patients with sacral fractures after posterior instrumented spinal fusion, including the sacrum, were retrospectively identified and matched 2:1 with non fracture controls based on gender, age, and number of levels fused. Patients with concurrent spinopelvic fixation or missing preoperative computed tomography (CT) imaging were excluded. Preoperative sagittal balance was assessed using lateral radiographs. Quantitative computed tomography (QCT) assessment included standard measurements at L1/L2 and additional experimental measurements of the S1 body and sacral ala. RESULTS: Twenty-one patients with sacral fracture were matched to non fracture controls. The majority of the patients with sacral fracture was female (76.2%) and of advanced age (mean 66.4 years). Fracture and control groups were well matched with respect to gender, age, and number of levels fused. Standard measurements at L1/L2 showed no significant difference in BMD between the fracture and the control groups (109.9 mg/cm3 vs. 116.4 mg/cm3, p=.414). Similarly, there was no significant BMD differences between the groups using the experimental measurements of the S1 body (183.6 mg/cm3 vs. 176.2 mg/cm3, p=.567) and the sacral ala (8.9 mg/cm3 vs. 4.8 mg/cm3, p=.616). Mean preoperative pelvic incidence-lumbar lordosis mismatch and pelvic tilt were not significantly different between the groups. Univariate conditional logistic regression analysis revealed that the odds of experiencing a sacral fracture was approximately six times higher for obese patients compared with normal or underweight patients. After controlling for BMI in multivariate conditional logistic regression models, BMD was still not significantly associated with the odds of experiencing sacral fractures. CONCLUSIONS: To our knowledge, this is the first study to assess the association of preoperative BMD measured by QCT, pelvic parameters, and BMI with postoperative sacral fractures in a large patient cohort. Interestingly, our data do not show any difference in preoperative pelvic parameters and BMD between the groups. This is in line with previous reports that indicate only a few patients with sacral fracture after fusion surgery have clear evidence of osteoporosis. Bone mineral density as a measure of bone quantity, rather than bone quality, may not be as important in these fractures as previously thought. Obesity, however, was associated with higher odds of experiencing postoperative sacral fractures. The present study thereby challenges the widespread concept that obesity is a protective factor against fractures in the elderly. In summary, our results suggest that BMI and gender, more than pelvic parameters and BMD, are risk factors for postoperative sacral fractures. PMID- 29792999 TI - Does solid fusion eliminate rod fracture after pedicle subtraction osteotomy in ankylosing spondylitis-related thoracolumbar kyphosis? AB - BACKGROUND CONTEXT: Rod fracture (RF) has a negative impact on the surgical outcome of patients with ankylosing spondylitis (AS) after lumbar pedicle subtraction osteotomy (PSO). However, there is a paucity of published studies analyzing the risk factors for RF in PSO-treated patients with AS with thoracolumbar kyphosis. PURPOSE: The objective of this study was to investigate the risk factors for RF after PSO for thoracolumbar kyphosis secondary to AS. STUDY DESIGN/SETTING: This is a retrospective single-center study. PATIENT SAMPLE: Patients with AS who underwent PSO for thoracolumbar kyphosis between January 2002 and December 2016 were included. OUTCOME MEASURES: Demographic data, including age, sex, body mass index, and smoking status, were summarized. The surgical data analyzed included the levels of osteotomy, the fusion levels, the upper instrumented vertebra, the lower instrumented vertebra, the osteotomy site, the rod material, the rod diameter, and the rod contour angle (RCA). Radiographic parameters included the sagittal vertical axis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. Radiographic parameters were measured at baseline, immediately after the operation, and at the final follow-up. Adequate ossification of the anterior longitudinal ligament (ALL) at the PSO level was defined by a total bony bridge. Adequate ossification of the ALL was also measured at baseline, immediately after the operation, and at the final follow-up. METHODS: Patients with a minimum of 2 years' follow-up or patients who developed RF were enrolled in the study. Recruited patients were divided into the RF group and the no-RF group based on whether they developed RF. Patient demographics, operative data, radiographic parameters, and adequate ossification of the ALL were analyzed to determine the risk factors for RF. For patients with RF, the fusion status at the PSO level, the time course to the development of RF, the site of RF, and the corresponding solution were also recorded. RESULTS: Rod fracture occurred in 11 (8.9%) of the 123 recruited patients. Solid fusion at the PSO level was found in all patients in the RF group. The average duration to the onset of RF was 31.4 months (range, 12-68 months). All RFs occurred at or immediately adjacent to the PSO level. The RCA was greater in the RF group than in the no-RF group (27.8 degrees vs 22.9 degrees , p=.031). A greater proportion of patients with a rod diameter of 5.50 mm were found in the RF group than in the no-RF group (100.0% vs 68.8%, p=.033). There was a larger proportion of patients with adequate ossification of the ALL at the final follow-up visit in the no-RF group than in the RF group (67.0% vs 27.3%, p=.018). Multivariate analyses demonstrated that the RCA (odds ratio, 1.174; 95% confidence interval, 1.018-1.354; p=.028) and adequate ossification of the ALL at the final follow-up visit (odds ratio, 0.079; 95% confidence interval, 0.014-0.465; p=.005) were independent factors for RF. Notably, revision surgery was performed among six patients, whereas conservative treatment was used for the remaining five patients. CONCLUSIONS: In patients with AS after PSO for thoracolumbar kyphosis with solid fusion at the PSO level, the incidence of RF was 8.9%. Rod diameter was identified as a risk factor for RF. Furthermore, the RCA was identified as an independent risk factor for RF. In contrast, adequate ossification of the ALL around the PSO level at the final follow-up visit was identified as an independent protective factor for RF. PMID- 29793000 TI - Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model. AB - BACKGROUND CONTEXT: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. STUDY DESIGN: Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. METHODS: We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. RESULTS: In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05). CONCLUSIONS: Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis. PMID- 29793001 TI - Health literacy in chronic disease management: a matter of interaction. AB - Health literacy plays a crucial role in chronic disease management. To comprehensively manage chronic conditions on a daily basis, individuals must be able to assess, understand, evaluate, and use health information. Several key publications emphasize that health literacy is not merely a matter of individual skills but that it is highly dependent on the accessibility of health-care systems, the communication skills of health-care professionals, and the level of complexity of the health information. However, the literature indicates that health literacy is mainly framed and measured as an individual attribute in research. Focusing health literacy research solely on the individual, rather than also including the health-care context, limits our understanding of the type of actions that should be undertaken to facilitate a person's access to and understanding, evaluation and use of health information. This commentary highlights the importance of interpreting the concept of health literacy as a dynamic construct that emerges from the interaction between patients/citizens and health-care systems, organizations, and professionals. This approach has the potential to fill a gap in our understanding of the link between health literacy and chronic disease management. Such an understanding would facilitate the development of comprehensive health literacy measurement instruments and interventions to enhance health literacy. PMID- 29793003 TI - Off-label prescription: experience is a gloomy lantern that does not even illuminate its bearer. PMID- 29793002 TI - Rasch analysis suggested that items from the template for intervention description and replication (TIDieR) checklist can be summed to create a score. AB - OBJECTIVE: The aim of this study was to construct and evaluate a summary score of reporting completeness based on the Template for Intervention Description and Replication (TIDieR). STUDY DESIGN AND SETTING: We included 200 reports published in 2013 randomly selected from the Physiotherapy Evidence Database. We summed the scores for the 12 items for the intervention and control groups for each trial to create a summary score from 0 to 24. Rasch analysis was used to investigate the item hierarchy, category function and reliability of the TIDieR checklist and determine the extent to which the summary score can be considered an interval level measure. RESULTS: The data fit the Rasch model suggesting the summary score is able to assess the completeness of reporting. The items appeared to target the study sample well (average report measure was 0.48 [0.87] compared to the average item measure of 0.0 [1.82]), and progressed in a logical manner, suggesting the summary score can be used as a single variable. The low internal consistency (0.62) suggests the summary score may only be able to discriminate between the least and most detailed reports. CONCLUSIONS: Our results support the use of the TIDieR summary score; however, we encourage the replication of our study in an independent data set. PMID- 29793004 TI - Statistician credit for collaboration requires extending the number of cited authors in research publications. PMID- 29793005 TI - The Delta likelihood ratio does not incorporate study power. Author response. PMID- 29793006 TI - The delta likelihood ratio does not incorporate study power. PMID- 29793007 TI - Minimum clinically important differences in chronic pain vary considerably by baseline pain and methodological factors: systematic review of empirical studies. AB - BACKGROUND: The minimum clinically important difference (MCID) is used to interpret the relevance of treatment effects, e.g., when developing clinical guidelines, evaluating trial results or planning sample sizes. There is currently no agreement on an appropriate MCID in chronic pain and little is known about which contextual factors cause variation. METHODS: This is a systematic review. We searched PubMed, EMBASE, and Cochrane Library. Eligible studies determined MCID for chronic pain based on a one-dimensional pain scale, a patient-reported transition scale of perceived improvement, and either a mean change analysis (mean difference in pain among minimally improved patients) or a threshold analysis (pain reduction associated with best sensitivity and specificity for identifying minimally improved patients). Main results were descriptively summarized due to considerable heterogeneity, which were quantified using meta analyses and explored using subgroup analyses and metaregression. RESULTS: We included 66 studies (31.254 patients). Median absolute MCID was 23 mm on a 0-100 mm scale (interquartile range [IQR] 12-39) and median relative MCID was 34% (IQR 22-45) among studies using the mean change approach. In both cases, heterogeneity was very high: absolute MCID I2 = 99% and relative MCID I2 = 96%. High variation was also seen among studies using the threshold approach: median absolute MCID was 20 mm (IQR 15-30) and relative MCID was 32% (IQR 15-41). Absolute MCID was strongly associated with baseline pain, explaining approximately two-thirds of the variation, and to a lesser degree with the operational definition of minimum pain relief and clinical condition. A total of 15 clinical and methodological factors were assessed as possible causes for variation in MCID. CONCLUSIONS: MCID for chronic pain relief vary considerably. Baseline pain is strongly associated with absolute, but not relative, measures. To a much lesser degree, MCID is also influenced by the operational definition of relevant pain relief and possibly by clinical condition. Explicit and conscientious reflections on the choice of an MCID are required when classifying effect sizes as clinically important or trivial. PMID- 29793008 TI - Qualitative research is a fundamental scientific process. AB - By framing the investigation of scientific inquiry around Plato's "arch of knowledge", we argue that qualitative inquiry is essential to the scientific process. We propose that because qualitative research applies a systematic and self-critical approach to induction and deduction, it should be considered a fundamental scientific enterprise. PMID- 29793009 TI - Evidence on the measurement properties of health-related quality of life instruments is largely missing in patients with low back pain: A systematic review. AB - OBJECTIVE: To synthesize the measurement properties of six health-related quality of life instruments (Short Form 36 [SF-36], Short Form 12 [SF-12], EuroQol 5D-3L [EQ-5D-3L], EuroQol 5D-5L [EQ-5D-5L], Nottingham Health Profile (NHP), and Patient-Reported Outcome Measurement Information System Global Health [PROMIS-GH 10]) in patients with low back pain (LBP). STUDY DESIGN AND SETTING: Six electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SportDiscus, and Google Scholar) were searched (July 2017). Studies assessing any measurement property in nonspecific LBP patients were included. Two reviewers independently screened the articles and assessed the risk of bias (COSMIN checklist). Consensus-based criteria were used to rate measurement properties results as sufficient, insufficient, or inconsistent; a modified GRADE approach was adopted for evidence synthesis. RESULTS: High quality evidence was found for insufficient construct validity of SF-36 summary scores, and EQ-5D-3L utility and visual analogue scale scores. Moderate evidence was found for sufficient construct validity of SF-12 physical summary score and inconsistent responsiveness of EQ-5D-3L utility score. Very low quality evidence was found on each instrument's content validity; very low to low evidence underpinned the other assessed measurement properties. EQ-5D 5L, NHP and PROMIS Global Health-10 were not evaluated in LBP patients. CONCLUSION: Documentation of the measurement properties of health-related quality of life instruments in LBP is incomplete. Future clinimetric studies should prioritize content validity. PMID- 29793010 TI - Restoration of Autologous Arteriovenous Fistula by Removal of the Occluded Short Venous Part and Venovenous End-To-End Anastomosis in a Hemodialysis Patient. AB - Standard salvage procedures for occuluded autologous arteriovenous fistula (AVF) in a hemodialysis patient are endovascular and/or surgical therapy. When endovascular therapy and thrombectomy prove unsuccessful, it is most likely that creating a new AVF or arteriovenous graft will be considered. However, if the occuluded venous part is short, we have adopted an operative technique for repair of AVF by removal of the occluded short venous part and venovenous end-to-end anastomosis. To our knowledge, the efficacy and clinical course of restoration of AVF by the technique have not been reported to date. Here, we describe the technique and report the successful treatment of a hemodialysis patient who developed AVF occlusion. PMID- 29793011 TI - Thoracic Endovascular Aortic Repair versus Best Medical Treatment for High-Risk Type B Intramural Hematoma: A Systematic Review of Clinical Studies. AB - BACKGROUND: To date, thoracic endovascular aortic repair (TEVAR) for type B aortic dissection is favorable, but TEVAR for type B intramural hematoma (IMH) remains uncertain. There are numerous clinical (e.g., refractory pain) and radiologic (e.g., IMH thickness) factors that are reported to be associated with IMH progression, challenging the treatment for high-risk type B IMH with high risk factors in clinical practice. OBJECTIVE: The objective of the study was to perform a systematic review of clinical studies to investigate outcomes of TEVAR + best medical treatment (BMT) and BMT in the treatment of high-risk type B IMH. METHODS: The online databases of PubMed, MEDLINE, EMBASE, CNKI, Google Scholar, and Cochrane as well as some journals majoring in endovascular surgery and interventional therapy were searched on September 1, 2017. Observational studies that reported the effect of TEVAR and BMT on type B IMH were included. Two independent reviewers performed methodological assessment and data extraction. Random and fixed effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out. RESULTS: In all 6 included studies, the total number of patients with type B IMH was 237 and 123 patients received TEVAR + BMT. There was a significantly higher IMH regression rate among patients undergoing TEVAR + BMT compared with BMT (odds ratios [OR] 10.0, 95% confidence interval [CI] 3.43-29.4). There were a significantly lower IMH progress rate and aortic-related death rate among patients undergoing TEVAR + BMT compared with BMT (OR 0.239, 95% CI 0.075-0.758; OR 0.248, 95% CI 0.085 0.725). When the study of Ye K et al. was excluded, the results showed no statistically significant differences. CONCLUSIONS: Combined data from the present study demonstrate that TEVAR + BMT results in significantly higher IMH regression rate, lower IMH progression, and lower aortic-related death rate compared with BMT in high-risk type B IMH patients. PMID- 29793012 TI - Endovascular Repair of a Penetrating Aortic Ulcer with a Custom-made Relay Stent Graft Featuring a Single Celiac Trunk Fenestration and a Superior Mesenteric Artery Scallop. AB - We report the case of a 70-year-old man with an asymptomatic, fast-growing, paraceliac penetrating aortic ulcer (PAU). Guidelines recommend endovascular repair if an asymptomatic PAU shows a mean growth rate >=5 mm per year: this patient's maximum aortic diameter was 47 mm but had increased 10 mm in the previous year. The very short sealing zones required a custom-made stent graft. A custom-made relay stent graft comprises a single celiac trunk fenestration, a superior mesenteric artery (SMA) scallop measured according to SMA ostium size, an uncovered distal stent, and 6-mm tapering was used with technical and clinical success. PMID- 29793013 TI - May-Thurner Syndrome Presenting as Acute Unexplained Deep Venous Thrombosis. AB - May-Thurner syndrome (MTS) is a rare cause of deep venous thrombosis and occurs due to an anatomic anomaly which produces chronic compression of the left common iliac vein by the overlying right common iliac artery when it passes between the right common iliac artery and the spine. Prolonged compression on the vein potentiates thrombus formation by impairing the intima and by leading to the development of membranes within the lumen that may decrease and/or block venous flow. In this case presentation, we elaborate on a case of a 43-year-old woman who presented with worsening left leg swelling and pain. The patient was diagnosed with MTS and underwent successful stent placement to relieve the compressed vein. PMID- 29793014 TI - Calf Muscle Oxygen Saturation during 6-Minute Walk Test and Its Relationship with Walking Impairment in Symptomatic Peripheral Artery Disease. AB - BACKGROUND: Impaired microcirculation is associated with poor walking capacity in symptomatic peripheral artery disease (PAD) patients during treadmill test; however, this test does not simulate the efforts of daily walking of these patients. Thus, the aim of the study was to describe the microcirculation responses during a 6-minute walk test (6MWT) and to analyze the relationship between microcirculation indicators and walking impairment in symptomatic PAD patients. METHODS: Thirty-four patients were included (mean age = 67.6 +/- 11.2 years). Their clinical characteristics were collected, and they performed a 6MWT, in which the initial claudication distance (ICD) and total walking distance (TWD) were recorded. During and after the 6MWT, calf muscle oxygen saturation (StO2) parameters were monitored continuously to measure microcirculation behavior. The association between calf muscle StO2 parameters and walking impairment were analyzed by Pearson or Spearman correlations. RESULTS: Walking impairment was not associated with any StO2 parameters during exercise. In contrast, after 6MWT, recovery time of StO2 (r = -0.472, P = 0.008) and recovery time to maximal StO2 (r = -0.402, P = 0.019) were negatively correlated with ICD. Furthermore, the distance walked under claudication symptoms (DeltaTWD-ICD) was positively correlated with recovery time to maximal StO2 (r = 0.347, P = 0.048). CONCLUSIONS: In symptomatic PAD patients, shorter ICD values during a 6MWT are associated with a delayed recovery in calf muscle StO2 after exercise. Calf muscle StO2 parameters decrease subtly during 6MWT, suggesting that the degree of ischemia in the calf muscle during ground walking, simulating efforts of the daily walking, is relatively low. PMID- 29793015 TI - Right Atrial Anomalous Muscle Bundle Presenting with Acute Superior Vena Cava Syndrome and Pulmonary Embolism: Surgical Management. AB - BACKGROUND: An anomalous muscle bundle (AMB) crossing the right atrial cavity represents a pathologic finding with unproved clinical significance. This congenital anomaly may be difficult to recognize via echocardiography and could be confused with other intracavitary lesions. METHODS: We report the case of a 53 year-old woman presented to the cardiovascular service with acute superior vena cava (SVC) syndrome and submassive pulmonary embolism. RESULTS: The patient underwent venography, confirming SVC stenosis. A ventilation/perfusion lung scan showed 2 sizable perfusion defects because of pulmonary embolism. Magnetic resonance imaging and echocardiography imaging demonstrated a right atrium (RA) mass. Surgery was then carried out using standard cardiopulmonary bypass; the right atrial muscle bundle was excised, and SVC reconstruction was performed. The patient was discharged uneventfully and remains symptom-free at 2-year follow-up. CONCLUSIONS: In cases of nonmalignant pathology of SVC syndrome, appropriate studies should be conducted to exclude potential congenital abnormalities such as this AMB in the RA. Open-heart surgery is a viable treatment option in select cases. PMID- 29793017 TI - Colonic Ischemia after Standard Endovascular Abdominal Aortic Aneurysm Repair, a Rare but Dangerous Complication. AB - Colonic ischemia (CI) after abdominal aortic aneurysm repair, although rare, is associated with severe prognosis. Endovascular aneurysm repair (EVAR) is becoming the standard of practice in most vascular centers, and it also may reduce CI incidence in comparison with conventional open repair. We report 2 cases of fatal CI after 636 standard EVAR procedures performed at our institution, from January 1998 to December 2017. Both patients were electively treated by highly skilled operators. In one patient, presenting early CI, EVAR procedure was complicated by intraoperative common iliac artery rupture. The other one, presenting CI in seventh postoperative day, had a history of previous left hemicolectomy. In both patients, CI with leakage of fecal material in the abdominal cavity was confirmed by surgical exploration. Only few cases of CI after EVAR have been reported in literature, and the etiology of this complication remains uncertain. While saving the inferior mesenteric artery is almost impossible during standard EVAR, the preservation of hypogastric arteries could play an important role, especially after colonic surgery, but other factors should also be considered. Our preliminary, although limited experience, seems to suggest that in CI developing, intraoperative persistent hypotension and hypogastric branches distal embolization have both a role that should be better addressed. PMID- 29793016 TI - Multiple Idiopathic Aneurysms in a 6-Year-Old Boy. AB - We report the rare case of a young boy affected by idiopathic multiple aneurysms at different arterial locations who was treated at our institution with different surgical and endovascular techniques. PMID- 29793018 TI - Image Fusion and 3-Dimensional Roadmapping in Endovascular Surgery. AB - Practitioners of endovascular surgery have historically used 2-dimensional (2D) intraoperative fluoroscopic imaging, with intravascular contrast opacification, to treat complex 3-dimensional (3D) pathology. Recently, major technical developments in intraoperative imaging have made image fusion techniques possible, the creation of a 3D patient-specific vascular roadmap based on preoperative imaging which aligns with intraoperative fluoroscopy, with many potential benefits. First, a 3D model is segmented from preoperative imaging, typically a computed tomography scan. The model is then used to plan for the procedure, with placement of specific markers and storing of C-arm angles that will be used for intraoperative guidance. At the time of the procedure, an intraoperative cone beam computed tomography is performed, and the 3D model is registered to the patient's on-table anatomy. Finally, the system is used for live guidance in which the 3D model is codisplayed with overlying fluoroscopic images. There are many applications for image fusion in endovascular surgery. We have found it to be particularly useful for endovascular aneurysm repair (EVAR), complex EVAR, thoracic EVAR, carotid stenting, and for type 2 endoleaks. Image fusion has been shown in various settings to lead to decreased radiation dose, less iodinated contrast use, and shorter procedure times. In the future, fusion models may be able to account for vessel deformation caused by the introduction of stiff wires and devices, and the user-dependent steps may become more automated. In its current form, image fusion has already proven itself to be an essential component in the planning and success of complex endovascular procedures. PMID- 29793019 TI - Factors Predicting Noncompliance with Follow-up after Endovascular Aneurysm Repair. AB - BACKGROUND: Although the potential for complications after endovascular aneurysm repair (EVAR) mandates lifetime follow-up, noncompliance with follow-up has been shown to be as high as 57%. We sought to investigate the incidence of noncompliance with follow-up in our patient population and to identify risk factors associated with this to allow implementation of targeted strategies to prevent loss to follow-up. METHODS: We carried out a review of consecutive patients undergoing EVAR at 2 Sydney hospitals between 1995 and 2015. Patients noncompliant with standard follow-up were compared with a control group of compliant patients. Data collected included baseline clinical characteristics, perioperative complications, and postoperative complications, as well as distance from treating centers. RESULTS: During the study period, 1,482 patients underwent EVAR, of which 338 patients (22.8%) were not compliant with follow-up. Patients noncompliant with follow-up were significantly more likely to be younger, have hypertension, and be current smokers. Patients who did not attend follow-up were also significantly more likely to be from a non-English-speaking background (28.4 vs. 17.9%; P = 0.01) and live closer to the treating institution (109 +/- 151.5 vs. 150 +/- 208.34 km; P = 0.01). CONCLUSIONS: Follow-up after EVAR remains suboptimal. The present study serves to demonstrate that several factors, especially current smoking and a non-English-speaking background, are associated with poor compliance with follow-up after EVAR in our patient population and represent a potential area of intervention to improve compliance. PMID- 29793020 TI - EphA2 stimulates VCAM-1 expression through calcium-dependent NFAT1 activity. AB - Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-kappaB (NF-kappaB/p65) and nuclear factor of activated T-cells (NFAT). While ephrin-A1 failed to induce endothelial NF-kappaB activation, NF-kappaB inhibitors prevented ephrin-A1 induced VCAM-1 expression, suggesting basal NF-kappaB activity is required. In contrast, ephrin-A1 induced a robust EphA2-dependent increase in NFAT activation, and mutation of the NF-kappaB/NFAT-binding sites in the VCAM-1 promoter blunted ephrin-A1-induced promoter activity. NFAT activation classically occurs through calcium-dependent calcineurin activation, and inhibiting NFAT signaling with calcineurin inhibitors (cyclosporine A, FK506) or direct NFAT inhibitors (A 285222) was sufficient to block ephrin-A1-induced VCAM-1 expression. Consistent with robust NFAT activation, ephrin-A1-induced an EphA2-dependent calcium influx in endothelial cells that was required for ephrin-A1-induced NFAT activation and VCAM-1 expression. This work provides the first data showing EphA2-dependent calcium influx and NFAT activation and identifies NFAT as a novel EphA2-dependent proinflammatory pathway in endothelial activation. PMID- 29793021 TI - Phosphoinositide 3-kinase p110alpha negatively regulates thrombopoietin-mediated platelet activation and thrombus formation. AB - Phosphoinositide 3-kinase (PI3K) plays an important role in platelet function and contributes to platelet hyperreactivity induced by elevated levels of circulating peptide hormones, including thrombopoietin (TPO). Previous work established an important role for the PI3K isoform; p110beta in platelet function, however the role of p110alpha is still largely unexplored. Here we sought to investigate the role of p110alpha in TPO-mediated hyperactivity by using a conditional p110alpha knockout (KO) murine model in conjunction with platelet functional assays. We found that TPO-mediated enhancement of collagen-related peptide (CRP-XL)-induced platelet aggregation and adenosine triphosphate (ATP) secretion were significantly increased in p110alpha KO platelets. Furthermore, TPO-mediated enhancement of thrombus formation by p110alpha KO platelets was elevated over wild-type (WT) platelets, suggesting that p110alpha negatively regulates TPO mediated priming of platelet function. The enhancements were not due to increased flow through the PI3K pathway as phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) formation and phosphorylation of Akt and glycogen synthase kinase 3 (GSK3) were comparable between WT and p110alpha KO platelets. In contrast, extracellular responsive kinase (ERK) phosphorylation and thromboxane (TxA2) formation were significantly enhanced in p110alpha KO platelets, both of which were blocked by the MEK inhibitor PD184352, whereas the p38 MAPK inhibitor VX-702 and p110alpha inhibitor PIK-75 had no effect. Acetylsalicylic acid (ASA) blocked the enhancement of thrombus formation by TPO in both WT and p110alpha KO mice. Together, these results demonstrate that p110alpha negatively regulates TPO mediated enhancement of platelet function by restricting ERK phosphorylation and TxA2 synthesis in a manner independent of its kinase activity. PMID- 29793022 TI - Superhydrophobic graphene-based sponge as a novel sorbent for crude oil removal under various environmental conditions. AB - Mechanical recovery of oils using oil sorbents is one of the most important approaches to manage marine oil spills. However, the properties of the oils spilled into sea are influenced by external environmental conditions. In this study, we present a graphene-based (GB) sponge as a novel sorbent for crude oil removal and compare its performance with that of a commercial sorbent sheet under various environmental parameters. The GB sponge with excellent superhydrophobic and superoleophilic characteristics is demonstrated to be an efficient sorbent for crude oils, with high sorption capacity (up to 85-95 times its weight) and good reusability. The crude-oil-sorption capacity of our GB sponge is remarkably higher (about 4-5 times) than that of the commercial sheet and most other previously reported sponge sorbents. Moreover, several challenging environmental conditions were examined for their effects on the sorption performance, including the weathering time of oils, seawater temperature, and turbulence (wave effect). The results show that the viscosity of the oil increased with increasing weathering time or decreasing temperature; therefore, the sorption rate seemed to decrease with longer weathering times and lower temperatures. Turbulence can facilitate inner sorption and promote higher oil sorption. Our results indicate that the extent of the effects of weather and other environmental factors on crude oil should be considered in the assessment of the effective adsorption capacity and efficiency of sorbents. The present work also highlights the widespread potential applications of our GB sponge in marine spilled-oil cleanup and hydrophobic solvent removal. PMID- 29793023 TI - Kinetics and stereochemistry of LinB-catalyzed delta-HBCD transformation: Comparison of in vitro and in silico results. AB - LinB is a haloalkane dehalogenase found in Sphingobium indicum B90A, an aerobic bacterium isolated from contaminated soils of hexachlorocyclohexane (HCH) dumpsites. We showed that this enzyme also converts hexabromocyclododecanes (HBCDs). Here we give new insights in the kinetics and stereochemistry of the enzymatic transformation of delta-HBCD, which resulted in the formation of two pentabromocyclododecanols (PBCDols) as first- (P1delta, P2delta) and two tetrabromocyclododecadiols (TBCDdiols) as second-generation products (T1delta, T2delta). Enzymatic transformations of delta-HBCD, alpha1-PBCDol, one of the transformation products, and alpha2-PBCDol, its enantiomer, were studied and modeled with Michaelis-Menten (MM) kinetics. Respective MM-parameters KM, vmax, kcat/KM indicated that delta-HBCD is the best LinB substrate followed by alpha2- and alpha1-PBCDol. The stereochemistry of these transformations was modeled in silico, investigating respective enzyme-substrate (ES) and enzyme-product (EP) complexes. One of the four predicted ES-complexes led to the PBCDol product P1delta, identical to alpha2-PBCDol with the 1R,2R,5S,6R,9R,10S-configuration. An SN2-like substitution of bromine at C6 of delta-HBCD by Asp-108 of LinB and subsequent hydrolysis of the alkyl-enzyme led to alpha2-PBCDol. Modeling results further indicate that backside attacks at C1, C9 and C10 are reasonable too, selectively binding leaving bromide ions in a halide pocket found in LinB. Docking with alpha2-PBCDol, also allowed productive enzyme binding. A TBCD-1,5 diol with the 1S,2S,5R,6R,9S,10R-configuration is the predicted second-generation product T1delta. In conclusion, in vitro- and in silico findings now allow a detailed description of step-wise enzymatic dehalohydroxylation reactions of delta-HBCD to specific PBCDols and TBCDdiols at A-resolution and predictions of their stereochemistry. PMID- 29793024 TI - Sedimentary record of plutonium in the North Yellow Sea and the response to catchment environmental changes of inflow rivers. AB - Plutonium (Pu) isotopes were first determined in surface and core sediment samples collected from the northern North Yellow Sea (NYS) to elucidate their source terms and deposition process as well as the response to catchment environmental changes of inflow rivers. 240Pu/239Pu atom ratios in all sediments showed the typical global fallout value of ~0.18 without any influences from the nuclear weapons tests conducted recently in the North Korea or early in the Pacific Proving Ground. The large variation of 239+240Pu activities (0.022-0.515 mBq/g) observed in surface sediments should be mainly attributed to the re suspension and transportation of fine sediments influenced by the Liaonan Costal Current. Based on the two 239+249Pu depth profiles with easily observed onset fallout levels (1952) and global fallout peaks (1963), 239+240Pu served as a valid time mark in the coastal sedimentary system. Riverine input Pu contributed only 15-27% to the total global fallout inventory (92.5-108.8 Bq/m2) in the northern NYS, much lower than that in the Yangtze River estuary (77-80%), indicating a better soil conservation in the northeast China due to higher forest coverage compared to the Yangtze River's drainage basin. The increase of riverine input Pu after 1980s reflected the more intense soil erosion degree caused by the land use and cover change due to the increment of human activities in the northeast China at the same period. Our results demonstrated that plutonium is a good indicator for studying sedimentary process and its response to the environment in the coastal area. PMID- 29793026 TI - Redistribution of Cs 137 introduced into montmorillonite in association with organic matter coming from biomass composting. AB - The adsorption and later bioavailability of 137Cs from the system humic acid (HA)/humic acid like compounds (HALC) and montmorillonite was investigated. The setup of the experiments should approach as much as possible natural conditions when 137Cs is introduced into soil with HALC from decomposed biomass. The significant differences were found in the trials containing various HA/HALC and also pure montmorillonite. The 137Cs was more available when it reached soil in association with HALC originated from compost than when it was adsorbed on stable humic acids. Moreover, the long term interaction of 137Cs with HALC led to decrease of 137Cs adsorbed on montmorillonite and increase of its bioavailable fraction. UV-Vis spectrometry and infrared spectroscopy showed the clear difference between HA, fresh HALC and old HALC which could partially explain the different results. PMID- 29793025 TI - Simultaneous immobilization of borate, arsenate, and silicate from geothermal water derived from mining activity by co-precipitation with hydroxyapatite. AB - The treatment of the geothermal water discharged through mining activity is a critical issue because the rate of discharge is 12,000 m3 per day and the discharge contains high concentrations of borate (>20 mg/L) and arsenate (ca. 0.4 mg/L) as well as silicate and carbonate. The simultaneous reduction of borate and arsenate concentrations to acceptable levels was successfully performed by co precipitation with hydroxyapatite (HAp). Although the coexisting high concentrations of carbonate act as a disturbing element, the co-precipitation equilibrium of borate was shifted to lower values by adjusting the P/Ca molar ratio, and the removal rate of borate was accelerated by using Al3+ additives, resulting in the efficient reduction of borate within 1 h. The initially immobilized boron in HAp is in the tetragonal form, which probably occupies the hydroxyl sites in HAp, gradually transforming into the trigonal form in the solid state, as interpreted by 1H NMR and 11B-NMR. The coexisting silicate was also immobilized in an ellestadite form, as confirmed by 29Si-NMR measurements. Arsenate and silicate were immobilized before borate in geothermal water. A dissolution assay of borate in the solid residues after co-precipitation with HAp verified the acceptable stability of borate, which is independent of the amount of added Al3+. PMID- 29793027 TI - Evaluation of the Fenton process effectiveness in the remediation of soils contaminated by gasoline: Effect of soil physicochemical properties. AB - The remediation of four different soils contaminated by gasoline was performed using Fenton processes. Herein, the effect of the main physicochemical characteristics of the soils in the Fenton performance is emphasized. Fenton processes were applied in a column system, with and without addition of soluble iron (II), using undisturbed soil samples collected in four regions of the Parana State (Brazil). Two groups of contaminants were monitored during the remediation process: BTEX (benzene, toluene, ethylbenzene and xylenes) and TRHs (total recoverable hydrocarbons). Superior degradation efficiencies were observed in the soils with elevated mineral iron content (Red Argisol, Red-Yellow Argisol and Red Latosol), while the soils with low iron content (Spodosol) presented comparable degradation efficiencies only in the presence of soluble Fe2+. Although the presence of mineral iron enabled the Fenton processes, a good correlation between the iron content and the degradation efficiency was not observed, suggesting a dependence on the chemical nature of the native iron. BTEX leaching was observed in all systems, suggesting that the process should be applied with caution, especially in soils with high drainage. PMID- 29793028 TI - Cytosolic distributions of highly toxic metals Cd and Tl and several essential elements in the liver of brown trout (Salmo trutta L.) analyzed by size exclusion chromatography and inductively coupled plasma mass spectrometry. AB - Cytosolic distributions of nonessential metals Cd and Tl and seven essential elements among compounds of different molecular masses were studied in the liver of brown trout (Salmo trutta) from the karstic Krka River in Croatia. Analyses were done by size exclusion high performance liquid chromatography and high resolution inductively coupled plasma mass spectrometry. Common feature of Cd and Tl, as highly toxic elements, was their distribution within only two narrow peaks. The increase of cytosolic Cd concentrations was reflected in marked increase of Cd elution within low molecular mass peak (maximum at ~15 kDa), presumably containing metallothioneins (MTs), which indicated successful Cd detoxification in brown trout liver under studied exposure conditions. Contrary, the increase of cytosolic Tl concentrations was reflected in marked increase of Tl elution within high molecular mass peak (maximum at 140 kDa), which probably indicated incomplete Tl detoxification. Common feature of the majority of studied essential elements was their distribution within more peaks, often broad and not well resolved, which is consistent with their numerous physiological functions. Among observed associations of essential metals/nonmetal to proteins, the following could be singled out: Cu and Zn association to MTs, Fe association to storage protein ferritin, and Se association to compounds of very low molecular masses (<5 kDa). The obtained results present the first step towards identification of metal-binding compounds in hepatic cytosol of brown trout, and thus a significant contribution to better understanding of metal fate in the liver of that important bioindicator species. PMID- 29793029 TI - Oxidative degradation of atenolol by heat-activated persulfate: Kinetics, degradation pathways and distribution of transformation intermediates. AB - Atenolol (ATL) has been widely detected in wastewater and aquatic environment. Although satisfactory removal of ATL from wastewater could be achieved, the mineralization ratio is usually low, which may result in the accumulation of its transformation products in the effluent and cause additional ecological risk to the environment. The aim of this study is to explore the effectiveness of heat activated persulfate (PS) in the removal of ATL from wastewater. Influencing factors including temperature, PS dosage, solution pH, existence of NO3-, Cl-, HCO3- and Suwannee river fulvic acid (SRFA) were examined. Complete removal of ATL was achieved within 40 min at pH 7.0 and 70 degrees C by using 0.5 mM PS. Inhibitive effects of HCO3- and FA had been observed on ATL oxidation, which was increased with the increase of their concentration. Sulfate radical (SO4-) was determined as the main reactive species by quenching experiment. Eight intermediates produced in ATL degradation were identified, and four degradation pathways were proposed based on the analysis of mass spectrum and frontier electron densities. The distribution of major intermediates was influenced by reaction temperature. Hydroxylation intermediates and deamidation intermediate were the most prominent at 50 degrees C and 60 degrees C, respectively. All intermediates were completely degraded in 40 min except P134 at 70 degrees C. Effective removal of TOC (74.12%) was achieved with 0.5 mM PS, pH 7.0 and 70 degrees C after 240 min. The results proved that heat activation of PS is a promising method to remove organic pollutants in wastewater. PMID- 29793030 TI - Sorption of perfluoroalkyl substances (PFASs) to an organic soil horizon - Effect of cation composition and pH. AB - Accurate prediction of the sorption of perfluoroalkyl substances (PFASs) in soils is essential for environmental risk assessment. We investigated the effect of solution pH and calculated soil organic matter (SOM) net charge on the sorption of 14 PFASs onto an organic soil as a function of pH and added concentrations of Al3+, Ca2+ and Na+. Often, the organic C-normalized partitioning coefficients (KOC) showed a negative relationship to both pH (Deltalog KOC/DeltapH = -0.32 +/- 0.11 log units) and the SOM bulk net negative charge (Deltalog KOC = -1.41 +/- 0.40 per log unit molc g-1). Moreover, perfluorosulfonic acids (PFSAs) sorbed more strongly than perfluorocarboxylic acids (PFCAs) and the PFAS sorption increased with increasing perfluorocarbon chain length with 0.60 and 0.83 log KOC units per CF2 moiety for C3-C10 PFCAs and C4, C6, and C8 PFSAs, respectively. The effects of cation treatment and SOM bulk net charge were evident for many PFASs with low to moderate sorption (C5-C8 PFCAs and C6 PFSA). However for the most strongly sorbing and most long-chained PFASs (C9-C11 and C13 PFCAs, C8 PFSA and perfluorooctane sulfonamide (FOSA)), smaller effects of cations were seen, and instead sorption was more strongly related to the pH value. This suggests that the most long-chained PFASs, similar to other hydrophobic organic compounds, are preferentially sorbed to the highly condensed domains of the humin fraction, while shorter-chained PFASs are bound to a larger extent to humic and fulvic acid, where cation effects are significant. PMID- 29793031 TI - Cloning, overexpression, and purification of a gene of unknown function of prophage loci from 'Candidatus Liberibacter asiaticus,' the destructive bacterial pathogen of huanglongbing disease in citrus plants. AB - Citrus Huanglongbing (HLB) or citrus greening is one of the most destructive diseases affecting citrus industry worldwide. The causal agent in Asia is a phloem-limited, Gram-negative bacterium, 'Candidatus Liberibacter asiaticus' (CLas). Within the genome of CLas lies prophage regions, classified as Type-A, B, C, and D. In particular, Type-D has been indicated to correlate with the blotchy mottle symptoms of citrus trees. Here we reported the cloning, overexpression, and purification of the ORF1, an open reading frame from the partial Type-D region of CLas obtained from an infected lime tree (Citrus aurantifolia Swingle). Overexpression of the ORF1 was toxic to the E. coli BL21(DE3), and the transient expression of ORF1 in Arabidopsis seedlings by Agrobacterium-mediated transformation exhibited rapid and total chlorosis of the seedlings within two days post-transformation. The native-PAGE of the purified protein showed multiple bands, indicative of various conformations in solution. The ESI-TOF mass spectrum confirmed the molecular weight of the purified ORF1 to be 15,364.3150 Da, corresponding to the [M+1]+ of the ORF1 without an N-terminal methionine. The protein predominantly consisted of alpha-helix as evidenced by circular dichroism (CD), and the transition toward random coil structure upon heating was reversible. The template-based modeling (I-TASSER) of the ORF1 indicated eight alpha-helices connected through variable loops. The simulated CD spectrum, generated from the atomic coordinates of the I-TASSER model, was notably similar to the experimental spectrum. Our report offers the basis for understanding the contributions of genes within Type-D prophage region toward the disease pathogenicity of citrus HLB. PMID- 29793032 TI - Phosphorylated and non-phosphorylated HCK kinase domains produced by cell-free protein expression. AB - Since phosphorylation is involved in various physiological events, kinases and interacting factors can be potential targets for drug discovery. For the development and improvement of inhibitors from the point of view of mechanistic enzymology, a cell-free protein synthesis system would be advantageous, since it could prepare mutant proteins easily. However, especially in the case of protein kinase, product solubility remains one of the major challenges. To overcome this problem, we prepared a chaperone-supplemented extract from Escherichia coli BL21 cells harboring a plasmid encoding a set of chaperone genes, dnaK, dnaJ, and grpE. We explored cell-disruption procedures and constructed an efficient protein synthesis system. Employing this system, we produced the kinase domain of human hematopoietic cell kinase (HCK) to obtain further structural information about its molecular interaction with one of its inhibitors, previously developed by our group (RK-20449). Lower reaction temperature improved the solubility, and addition of a protein phosphatase (YpoH) facilitated the homogeneous production of the non-phosphorylated kinase domain. Crystals of the purified product were obtained and the kinase-inhibitor complex structure was solved at 1.7 A resolution. In addition, results of kinase activity measurement, using a synthetic substrate, showed that the kinase activity was facilitated by autophosphorylation at Tyr416, as confirmed by the peptide mass mapping. PMID- 29793033 TI - Expression of Anabaena sensory rhodopsin is influenced by different codons of seven residues at the N-terminal region. AB - Microbial rhodopsins are well-known seven-transmembrane proteins that have been extensively studied for their structure and function. These retinal-binding proteins can be divided into two types. Type I is microbial rhodopsin, and type II (visual pigment) is expressed mostly in mammalian eyes. The two primary functions of type I rhodopsin are ion pumping activity and sensory transduction. Anabaena sensory rhodopsin (ASR) is a microbial rhodopsin with a specific function of photosensory transduction. ASR is expressed at moderate levels in Escherichia coli, but its expression level is lower compared to the general green light absorbing proteorhodopsin (GPR). In this study, full-length ASR was used to test the influence of codon usage on expression E. coli. Seven amino acids at the N-terminal region of ASR after the Met start codon were changed randomly using designed primers, which allowed for 8192 different nucleotide combinations. The codon changes were screened for the preferable codons that resulted in higher expression yield. Among the 57 selected mutations, 24 color-enhanced E. coli colonies contained ASR proteins, and they expressed ASR at a higher level than the bacteria with wild-type ASR codon usage. This result strongly suggests that the specific codon usage of only the N-terminal portion of a protein can increase the expression level of the entire protein. PMID- 29793034 TI - A case-control study about foetal trauma during caesarean delivery. AB - OBJECTIVE: The caesarean section rate is gradually increasing in most countries. The frequency of occurrence of foetal injury per birth is estimated to 1%. The majority of these injuries presents a low functional impact, but remains responsible for a significant neonatal morbidity. Even though the foetal risk factors are well documented in cases of vaginal birth, they have not been accurately identified for caesarean section. The aim of this study is to identify the risk factors for neonatal fracture during caesarean section. METHODS: We conducted a retrospective case-control study comparing complicated caesarean sections foetal fracture with uncomplicated caesarean sections in a tertiary teaching hospital. We collected all the caesarean sections carried out between 1st January 2003 and 1st September 2015 and selected those the medical files of which presented a foetal fracture diagnosis. RESULTS: We identified 10 fractures during the study period, including four skull fractures, three long bone fractures, three clavicle fractures. In all these cases there were no complications with a median perspective of six years (median=6, IQR=4). The push method, which is performed during a caesarean section at the second stage of labour, is identified as a risk factor for foetal trauma in our study (OR: 20.2 [2.8-116.85], p<0.01). A significant correlation was found between transverse lie and foetal trauma (OR: 16.67, CI [1.39; 123.18], p=0.0137). CONCLUSION: Foetal trauma during caesarean delivery is a rare event for which the prognosis is most often favourable. Data in the literature on the subject are minimal. This study highlighted transverse lie and the push method as risks factors for foetal fractures during caesarean sections. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. PMID- 29793036 TI - Breast cancer and ovarian tissue cryopreservation: Review of the literature. AB - INTRODUCTION: Ovarian tissue cryopreservation is a modern technique of fertility preservation, useful before using ovariotoxic therapies in the treatment of breast cancer. The aim of our literature review was to study ovarian cryopreservation experiences for women with breast cancer, to identify guidelines, constraints and results in the oncological and obstetrical fields. METHODS: We searched articles through the PubMed/Medline database, including all French and English references from January 2000 to October 2017. The combination of key words "breast cancer" and "ovarian tissue cryopreservation" allowed us to select 50 articles. We kept 18 publications which matched our subject. RESULTS: Sixteen cases of ovarian transplants among patients treated for breast cancer were published with 14 pregnancies, 11 births and 3 failures. Two cases of breast recurrences were published after ovarian grafting. However, the hindsight in this technique is limited, with a first transplant published in 2004 and only a low number of cases. PERSPECTIVES: A national census and comprehensive gathering of data among the patients treated for breast cancer using ovarian tissue cryopreservation would make it possible to better evaluate the occurrence of pregnancies and the carcinological risk of this technique. PMID- 29793035 TI - Assessment of fetal head engagement with transperineal ultrasound: Searching for the cutoff level. AB - PURPOSE: Engagement of the fetal head is a determinant element when deciding on operative vaginal delivery. In routine practice, engagement is a clinical diagnosis based on transvaginal digital examination. Transperineal ultrasound might provide complementary information useful for measuring the fetal head perineum distance (HPD). The purpose of this work was to determine the cutoff HPD distinguishing engagement from non-engagement. MATERIALS AND METHODS: This single center prospective study approved by the institutional review board was conducted between December 25, 2012 and August 31, 2015 in 411 nulliparous women; 20 did not provide informed consent and were excluded; analysis concerned 391 patients. Clinical diagnosis - engagement or non-engagement depending on results of the transvaginal digital examination (Farabeuf's and Demelin's signs) - was compared with the ultrasound HPD measurement. RESULTS: The clinical diagnosis was non engagement at complete dilatation in 96 patients (24.6%). The cutoff HPD distinguishing between engagement and non-engagement was 57mm (AUC 83.5% [95%CI 79.3-87.8]), with 75.0% [65.5-82.6] sensitivity, 75.9% [70.7-80.5] specificity, 50.3% [42.2-58.4] positive predictive value, and 90.3% [86.0-93.4] negative predictive value. CONCLUSIONS: In this series, the HPD cutoff distinguishing between engagement and non-engagement was 57mm. Below this cutoff level, the head should be considered engaged, beyond non-engaged. Nevertheless, the pertinence of this cutoff level is hampered by the imprecision of the gold standard used for the clinical diagnosis (transvaginal digital examination). In case of doubt, we recommend, in addition to considering the obstetrical setting, to combine transperineal ultrasound with transvaginal digital examination to avoid deleterious failure of operative vaginal delivery. PMID- 29793037 TI - Fetal supraventricular tachycardia and cystic fibrosis: Coincidence or association? Two case reports. AB - Prenatal diagnosis of cystic fibrosis (CF) is difficult and is mainly considered upon identification of digestive sonographic signs. Although such an association has never been described until now to our knowledge, we report two cases of fetal arrhythmia associated with cystic fibrosis. This association may be explained by the physiopathology of heart in the context of CF, but nevertheless needs to be confirmed by other reports. The prenatal diagnosis of CF is important in order to implement early appropriate care, with better prognosis. The finding of possibly new associated prenatal signs may then improve the global management of the disease. PMID- 29793039 TI - Antimicrobial resistance in the context of the Syrian conflict: Drivers before and after the onset of conflict and key recommendations. AB - Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress. PMID- 29793038 TI - Therapeutic drug monitoring and safety of voriconazole therapy in patients with Child-Pugh class B and C cirrhosis: A multicenter study. AB - OBJECTIVES: The purpose of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in patients with Child-Pugh class B and C cirrhosis. METHODS: Liver cirrhosis patients who had received the recommended voriconazole maintenance dose (group A) or halved maintenance dose (group B), orally or intravenously, were included. Voriconazole-related adverse events (AEs) were defined according to the Common Terminology Criteria for Adverse Events. RESULTS: A total of 110 trough plasma concentrations of voriconazole (Cmin) were measured in 78 patients. There was a significant difference in voriconazole Cmin between group A and group B (Cmin, 6.95+/ 3.42mg/l vs. 4.02+/-2.00mg/l; p<0.001). No significant difference in voriconazole Cmin between Child-Pugh class B and C cirrhosis patients was observed in either of the two groups. The international normalized ratio and co-medication with a CYP2C19 inhibitor had a significant effect on voriconazole Cmin in group B. The incidence of AEs in group A was 26.5% and in group B was 15.9%, and 87.5% of AEs developed within 7days after starting voriconazole treatment. CONCLUSIONS: These results suggest that the recommended dose and halved maintenance dose may be inappropriate in patients with Child-Pugh class B and C cirrhosis due to the high Cmin, and that voriconazole Cmin should be monitored earlier to avoid AEs. PMID- 29793040 TI - Quinones and nitroaromatic compounds as subversive substrates of Staphylococcus aureus flavohemoglobin. AB - In microorganisms, flavohemoglobins (FHbs) containing FAD and heme (Fe3+, metHb) convert NO. into nitrate at the expense of NADH and O2. FHbs contribute to bacterial resistance to nitrosative stress. Therefore, inhibition of FHbs functions may decrease the pathogen virulence. We report here a kinetic study of the reduction of quinones and nitroaromatic compounds by S. aureus FHb. We show that this enzyme rapidly reduces quinones and nitroaromatic compounds in a mixed single- and two-electron pathway. The reactivity of nitroaromatics increased upon an increase in their single-electron reduction potential (E17), whereas the reactivity of quinones poorly depended on their E17 with a strong preference for a 2-hydroxy-1,4-naphthoquinone structure. The reaction followed a 'ping-pong' mechanism. In general, the maximal reaction rates were found lower than the maximal presteady-state rate of FAD reduction by NADH and/or of oxyhemoglobin (HbFe2+O2) formation (~130 s-1, pH 7.0, 25 degrees C), indicating that the enzyme turnover is limited by the oxidative half-reaction. The turnover studies showed that quinones prefreqently accept electrons from reduced FAD, and not from HbFe2+O2. These results suggest that quinones and nitroaromatics act as 'subversive substrates' for FHb, and may enhance the cytotoxicity of NO. by formation of superoxide and by diverting the electron flux coming from reduced FAD. Because quinone reduction rate was increased by FHb inhibitors such as econazole, ketoconazole, and miconazole, their combined use may represent a novel chemotherapeutical approach. PMID- 29793042 TI - Aminergic neuromodulation of associative visual learning in harnessed honey bees. AB - The honey bee Apis mellifera is a major insect model for studying visual cognition. Free-flying honey bees learn to associate different visual cues with a sucrose reward and may deploy sophisticated cognitive strategies to this end. Yet, the neural bases of these capacities cannot be studied in flying insects. Conversely, immobilized bees are accessible to neurobiological investigation but training them to respond appetitively to visual stimuli paired with sucrose reward is difficult. Here we succeeded in coupling visual conditioning in harnessed bees with pharmacological analyses on the role of octopamine (OA), dopamine (DA) and serotonin (5-HT) in visual learning. We also studied if and how these biogenic amines modulate sucrose responsiveness and phototaxis behaviour as intact reward and visual perception are essential prerequisites for appetitive visual learning. Our results suggest that both octopaminergic and dopaminergic signaling mediate either the appetitive sucrose signaling or the association between color and sucrose reward in the bee brain. Enhancing and inhibiting serotonergic signaling both compromised learning performances, probably via an impairment of visual perception. We thus provide a first analysis of the role of aminergic signaling in visual learning and retention in the honey bee and discuss further research trends necessary to understand the neural bases of visual cognition in this insect. PMID- 29793043 TI - Type B Laparoscopic Radical Trachelectomy with Uterine Artery Preservation for Stage IB1 Cervical Cancer. AB - STUDY OBJECTIVE: Radical trachelectomy has emerged as a valuable fertility preserving treatment option for young women with early-stage cervical cancer [1]. Laparoscopic radical trachelectomy performed by trained surgeons can be a feasible and safe therapeutic option as a fertility-sparing surgical technique [2,3]. To the best of our knowledge, this is the first time the total laparoscopic approach of radical trachelectomy is being published. In this video, rather than the description of the technique step by step, we show how to conserve uterine arteries even if the importance of such conservation is questionable. DESIGN: A case report. SETTING: A tertiary referral center in Strasbourg, France. PATIENT: A 37-year-old patient with no medical history who presented with stage IB1 invasive epidermoid cervical cancer. INTERVENTION: In this video, we describe the fertility-sparing surgical procedure consisting of type B total laparoscopic radical trachelectomy with uterine artery preservation. The procedure consists of the following 10 steps: step 1, bilateral pelvic lymphadenectomy and opening of the para vesical fossa; step 2, opening of the pararectal fossa in between the ureter and the internal iliac artery on each side; step 3, ureteric dissection up to the ureteric canal; step 4, opening of the vesicouterine space and section of the vesicouterine ligament; step 5, posterior dissection with division of the uterosacral ligament approximately 20mm from the uterine insertion; step 6, section of the descending branch of the uterine artery and skeletonization of the ascending branch up to the uterine isthmus level; step 7, trachelectomy with a monopolar hook; step 8, laparoscopic isthmovaginal stitches; step 9, laparoscopic cerclage; and step 10, peritoneal closure. MEASUREMENTS AND MAIN RESULTS: The operative time was 420 minutes. The intraoperative blood loss was <200mL. The operation was performed successfully with no intraoperative complications. The resection margins were safe. The patient was discharged on day 4. After 2 months, no late complications or recurrence were detected, and the patient had normal menstruation. CONCLUSION: Type B laparoscopic radical trachelectomy with uterine artery preservation appears to be a safe option for women who intend to maintain their desire for a future pregnancy. PMID- 29793044 TI - Isolation of ferritin and its interaction with BmNPV in the silkworm, Bombyx mori. AB - Ferritin is a ubiquitous iron storage protein that plays an important role in host defence against pathogen infections. In the present study, native ferritin was isolated from the hemolymph of Bombyx mori using native-polyacrylamide gel electrophoresis (native-PAGE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results revealed that ferritin consisted of two subunits, designated as BmFerHCH and BmFerLCH. Previously integrated previous transcriptome and iTRAQ data showed that the two subunits were down-regulated in resistant silkworm strain BC9 and there was no obvious change in the expression levels of the subunits in susceptible silkworm strain P50 after BmNPV infection. Virus overlay assays revealed that B. mori ferritin as the form of heteropolymer had an interaction with B. mori nucleopolyhedrovirus (BmNPV), but it can't interact with BmNPV after depolymerisation. What's more, reverse transcription quantitative PCR (RT-qPCR) analysis suggested that BmFerHCH and BmFerLCH could be induced by bacteria, virus and iron. This is the first study to extract B. mori ferritin successfully and confirms their roles in the process of BmNPV infection. All these results will lay a foundation for further research the function of B. mori ferritin. PMID- 29793045 TI - Ophthalmomyiasis externa due to Oestrus ovis in a traveller returning from Greece. PMID- 29793047 TI - Transcript profiling of salt tolerant tobacco mutants generated via mutation breeding. AB - The main aim of the study is to identify the genes differentially, predominantly or specifically expressed in salt tolerant tobacco mutants, improved from Akhisar 97 and Izmir Ozbas varieties via mutation breeding, with respect to unstressed control plants. Seven tobacco mutants which have different salt tolerance capacities were evaluated by Gene Fishing analysis. Under stress conditions differentially expressed 100 reproducible bands were identified (74 of up regulated and 20 of down-regulated while 6 were unknown). 75 of differentially expressed genes (DEGs) were successfully extracted from the gel and sequence analyses were performed. Functional annotation of the DEGs was performed against Blastn by interrogating their sequences. The 65 salt-regulated differentially expressed genes showed similarity with known genes, while 6 of DEGs didn't show any genetic similarities with known genes. DEGs were classified in eleven functional categories involving the abiotic stress response, biotic stress response, energy metabolism, cellular transport, catalitic activity, protein modification, amino acid metabolism and transcription factors. All the mutants were evaluated for their regulatory mechanisms against salt stress. The current data reveal that these six DEGs should be identified by next generation sequencing techniques and functional analysis should be design to understand the role of these six differentially expressed genes of tobacco mutants in further studies to improve new genetic resources. PMID- 29793046 TI - Validation of the Revised Pretransplant Assessment of Mortality Score in Patients with Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. AB - Despite recent advances, allogeneic hematopoietic stem cell transplantation (allo HSCT) continues to be accompanied by a high rate of morbidity and mortality. Several scores have been developed to predict outcome after allo-HSCT. The recently revised Pretransplant Assessment of Mortality (PAM) score is based on patient age, donor type, disease risk, cytomegalovirus (CMV) serostatus of patient and donor, and forced expiratory volume in 1 second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent large cohort of patients with acute myelogenous leukemia (AML). We selected adult patients with AML who underwent a first allo-HSCT at the University Hospital of Dresden, a tertiary care hospital with a large transplantation program. All adult patients treated between January 1, 2003, and July 1, 2015, were included. The PAM score was calculated as described previously. Overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) after allo HSCT were analyzed. Age, AML type, sex match, CMV match, donor type, European Leukemia Net risk classification, type of conditioning, disease stage, and PAM score as a continuous variable were selected a priori for multivariate Cox regression analyses. A total of 544 patients met the inclusion criteria. The median patient age was 57 years. With a median follow-up of 47 months (range, 1 to 161 months), the estimated OS for the whole cohort at 4 years was 43%, with a CIR of 30% and an NRM of 31%. The probability of OS at 4 years was 65% for patients with a PAM score of 0, 52% in those with a PAM score of 1, 33% in those with a PAM score of 2, and 22% in those with a PAM score of 3 (P < .001, log-rank test). Both the CIR and NRM increased with higher PAM scores (P = .005 and P < .001, respectively, Gray test). In multivariate analysis, age (hazard ratio [HR], 1.02 per year; P = .004), disease stage (primary induction failure versus first complete remission (CR1); HR, 1.5; P = .03), and the PAM score (HR 1.04; P = .03) had a significant impact on OS. This is the first independent validation of the revised PAM score allowing for simple and valid estimation of transplantation outcomes. It can serve as an important tool in counseling patients with AML, as well as in designing future trials. PMID- 29793048 TI - DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse. AB - Depression is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis activity. A proposed mechanism to explain these alterations are changes in DNA methylation levels, secondary to early life adversity (ELA), at stress related genes. Two gene regions that have been implicated in the literature, the glucocorticoid receptor gene (NR3C1) exon 1F and the FKBP5 gene intron 7 were examined in 67 individuals (33 depressed patients and 34 controls). We investigated whether cortisol concentrations, evaluated in 25 depressed patients and 20 controls, and measures of ELA were associated with the degree of methylation at these candidate gene regions. Mean NR3C1 exon 1F DNA methylation levels were significantly increased in the depressed cohort and the degree of methylation was found to be positively associated with morning cortisol concentrations. DNA methylation levels at specific CG sites within the NR3C1 exon 1F were related to childhood emotional abuse severity. DNA methylation at CG38 was related to both HPA axis and childhood emotional abuse measures in the depressed group. No FKBP5 differences were revealed. Our findings suggest that hypermethylation at the NR3C1 exon 1F may occur in depression. This locus specific epigenetic change is associated with higher basal HPA axis activity, possibly reflecting acquired glucocorticoid receptor resistance. PMID- 29793041 TI - Selenoproteins in colon cancer. AB - Selenocysteine-containing proteins (selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual selenoproteins in this malignancy. Those selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions. PMID- 29793050 TI - Small-scale managed marine areas over time: Developments and challenges in a local Fijian reef fishery. AB - This paper investigates the Locally Managed Marine Area (LMMA) approach through looking at developments and challenges of community-based marine resource management over time, with a particular focus on Fiji in the South Pacific region. A diachronic perspective, based on two multi-method empirical studies, is used to exemplify the social complexities of the implementation of this LMMA approach in a specific island setting. This perspective connects local stakeholders' establishment and management of a LMMA covering their entire customary fishing rights area (iqoliqoli) with the national context articulated around the Fiji Locally Managed Marine Area (FLMMA) network, as well as with regional networking and international conservation dynamics. It especially explores the impacts of a small-scale marine closure (so-called tabu area) on the harvesting patterns in a portion of this LMMA, related aspects of formal and informal enforcement, and villagers' views of the health of their reef fishery. This case study reveals a lack of consensus on the current management of this closure as a conditionally-opened no-take area, whose temporary openings (re)produce social tensions, as well as a lack of consensus on the effects of this closure on the reef fishery, which is subject to poaching. The paper highlights that the articulation between conservation and extraction of marine resources, as well as between short-term and longer-term objectives of the community-based marine resource management in place, is a complex sociopolitical process even at the most local level. The discussion also points out that local observations and interpretations of coastal resource dynamics, and of the interplay between fishery and community changes, might be instrumental in addressing the limits of the area-based system of management inherent in the LMMA approach. These insights into both the development process of the LMMA approach and the challenges of its local implementation and maintenance efforts can be useful to consider the adjustments necessary for Fiji's achievement of its national coastal fisheries management strategy and its international ocean governance commitments. PMID- 29793049 TI - Psychometric validation of the Turkish nine-item Internet Gaming Disorder Scale Short Form (IGDS9-SF). AB - The main aims of the current study were to test the factor structure, reliability and validity of the nine-item Internet Gaming Disorder Scale-Short Form (IGDS9 SF), a standardized measure to assess symptoms and prevalence of Internet Gaming Disorder (IGD). In the present study participants were assessed with the IGDS9 SF, nine-item Internet Gaming Disorder Scale (IGDS) and the Young's Internet Addiction Test-Short Form (YIAT-SF). Confirmatory factor analyzes demonstrated that the factor structure (i.e., the dimensional structure) of the IGDS9-SF was satisfactory. The scale was also reliable (i.e., internally consistent with a Cronbach's alpha of 0.89) and showed adequate convergent and criterion-related validity, as indicated by statistically significant positive correlations between average time daily spent playing games during last year, IGDS and YIAT-SF scores. By applying the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) threshold for diagnosing IGD (e.g., endorsing at least five criteria), it was found that the prevalence of disordered gamers ranged from 0.96% (whole sample) to 2.57% (e-sports players). These findings support the Turkish version of the IGDS9-SF as a valid and reliable tool for determining the extent of IGD-related problems among young adults and for the purposes of early IGD diagnosis in clinical settings and similar research. PMID- 29793051 TI - Promising antileishmanial activity of novel imidazole antifungal drug luliconazole against Leishmania major: In vitro and in silico studies. AB - OBJECTIVES: Pentavalent antimonials have been used for the treatment of leishmaniasis for over 70 years, however they are limited by their toxicity. Unfortunately, the efficacy of first-line drugs for the treatment of leishmaniasis has decreased and resistance is noticeable. Luliconazole is a new azole with unique effects on fungi that has not yet been tested on Leishmania parasites. METHODS: In this study, the cytotoxicity and antileishmanial activity of luliconazole were evaluated in vitro against promastigotes and intracellular amastigotes of Leishmania major. The docking simulation with the target enzyme, sterol 14alpha-demethylase (CYP51) was performed using AutoDock 4.2 program. RESULTS: The IC50 (concentration of test compound required for 50% inhibition) against promastigotes revealed that luliconazole (IC50=0.19MUM) has greater potency than ketoconazole (KET), meglumine antimoniate (MA) and amphotericin B (AmB) (IC50 values of 135, 538 and 2.52MUM, respectively). Against the amastigote stage, luliconazole at a concentration of 0.07MUM decreased the mean infection rate and the mean number of amastigotes per macrophage more effectively than MA (P<0.004) and KET (P<0.043), but there was no difference compared with AmB (P>0.05). A docking study of luliconazole with the cytochrome P450 enzyme sterol 14alpha-demethylase (CYP51) revealed that this azole drug can properly interact with the target enzyme in Leishmania mainly via coordination with heme and multiple hydrophobic interactions. CONCLUSION: These results show the potent activity of luliconazole at extremely low concentrations against L. major. It may therefore be considered as a new candidate for treatment of leishmaniasis in the near future. PMID- 29793052 TI - LHP1 Interacts with ATRX through Plant-Specific Domains at Specific Loci Targeted by PRC2. AB - Heterochromatin Protein 1 (HP1) is a major regulator of chromatin structure and function. In animals, the network of proteins interacting with HP1 is mainly associated with constitutive heterochromatin marked by H3K9me3. HP1 physically interacts with the putative ortholog of the SNF2 chromatin remodeler ATRX, which controls deposition of histone variant H3.3 in mammals. In this study, we show that the Arabidopsis thaliana ortholog of ATRX participates in H3.3 deposition and possesses specific conserved domains in plants. We found that plant Like HP1 (LHP1) protein interacts with ATRX through domains that evolved specifically in land plant ancestors. Loss of ATRX function in Arabidopsis affects the expression of a limited subset of genes controlled by PRC2 (POLYCOMB REPRESSIVE COMPLEX 2), including the flowering time regulator FLC. The function of ATRX in regulation of flowering time requires novel LHP1-interacting domain and ATPase activity of the ATRX SNF2 helicase domain. Taken together, these results suggest that distinct evolutionary pathways led to the interaction between ATRX and HP1 in mammals and its counterpart LHP1 in plants, resulting in distinct modes of transcriptional regulation. PMID- 29793053 TI - Aggressive fluid and sodium restriction in decompensated heart failure with preserved ejection fraction: Results from a randomized clinical trial. AB - OBJECTIVES: Sodium and fluid restriction is commonly prescribed for heart failure patients. However, its role in the treatment of heart failure with preserved ejection fraction (HFpEF) remains unclear. The aim of this study was to compare the effect of a diet with sodium and fluid restriction with an unrestricted diet in patients admitted for decompensated HFpEF. METHODS: Patients were randomized to a diet with sodium (0.8 g/d) and fluid (800 mL/d) restriction (intervention group [IG]) or an unrestricted diet (control group [CG]) and followed for 7 d or hospital discharge. The primary outcome was weight loss. Secondary outcomes included clinical stability, perception of thirst, neurohormonal activation, nutrient intake, readmission, and mortality rate after 30 d. RESULTS: Fifty-three patients were included (30, IG; 23, CG). The mean ejection fraction was 62% +/- 8% for IG and 60% +/- 7% for CG (P = 0.44). Weight loss was similar in both groups, being 1.6 +/- 2.2 kg in the IG and 1.8 +/- 2.1 kg in CG (P = 0.49) as well as the reduction in the congestion score (IG = 3.4 +/- 3.5; CG = 3.8 +/- 3.4; P = 0.70). The daily perception of thirst was higher in the IG (P = 0.03). Lower energy consumption was seen in the IG (P <0.001). No significant between group differences at 30 d were found. CONCLUSIONS: Aggressive sodium and fluid restriction does not provide symptomatic or prognosis benefits, but does produce greater perception of thirst, may impair the patient's food intake, and does not seem to have an important neurohormonal effect in patients admitted for decompensated HFpEF. PMID- 29793055 TI - Fatty acid activation in thermogenic adipose tissue. AB - Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (beta oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in beta-oxidation and thermogenesis. The activation and deactivation of fatty acids are regulated by two sets of enzymes called acyl-CoA synthetases (ACS) and acyl-CoA thioesterases (ACOT), respectively. The expression levels of ACS and ACOT family members in thermogenic tissues will determine the substrate availability for beta-oxidation, and consequently the thermogenic capacity. Although the role of the majority of ACS and ACOT family members in thermogenesis remains unclear, recent proceedings link the enzymatic activities of ACS and ACOT family members to metabolic disorders and thermogenesis. Elucidating the contributions of specific ACS and ACOT family members to trafficking of fatty acids towards thermogenesis may reveal novel targets for modulating thermogenic capacity and treating metabolic disorders. PMID- 29793054 TI - Bacillus clausii inhibits bone loss by skewing Treg-Th17 cell equilibrium in postmenopausal osteoporotic mice model. AB - OBJECTIVES: Postmenopausal osteoporosis is one of most commonly occurring skeletal diseases leading to bone loss and fragility. Probiotics have been associated with various immunomodulatory properties and thus can be exploited to enhance bone health. In the present study, we report, to our knowledge for the first time, that oral administration of Bacillus clausii (BC) in postmenopausal osteoporotic (OVX) mice model enhances bone health. METHODS: BC was selected as probiotic of choice due to its established immunomodulatory properties. BC skews the Treg-Th17 cell balance in vivo by inhibiting osteoclastogenic Th17 cells and promoting antiosteoclastogenic Treg cell development in postmenopausal osteoporotic mice. Mice were divided into three groups (sham, OVX, and OVX + BC), and BC was administered orally in drinking water for 6 wk post-ovariectomy. At the end of experiment, mice were sacrificed and bones were analyzed for various parameters, along with lymphoid tissues for Treg-Th17 cells and serum cytokines. RESULTS: We observed that BC administration enhanced bone health. This effect of BC administration was found due to skewing of Treg-Th17 cell balance (enhanced Treg and decreased Th17 cells) in vivo. BC administration reduced levels of proinflammatory cytokines (interleukin [IL]-6, IL-17, IFN-gamma and tumor necrosis factor-alpha) and increased levels of anti-inflammatory cytokine (IL 10). CONCLUSIONS: The present study strongly supports and establishes the osteoprotective potential of BC leading to enhanced bone health in postmenopausal osteoporotic mice model. PMID- 29793056 TI - High myristic acid content in the cyanobacterium Cyanothece sp. PCC 8801 results from substrate specificity of lysophosphatidic acid acyltransferase. AB - Analysis of fatty acids from the cyanobacterium Cyanothece sp. PCC 8801 revealed that this species contained high levels of myristic acid (14:0) and linoleic acid in its glycerolipids, with minor contributions from palmitic acid (16:0), stearic acid, and oleic acid. The level of 14:0 relative to total fatty acids reached nearly 50%. This 14:0 fatty acid was esterified primarily to the sn-2 position of the glycerol moiety of glycerolipids. This characteristic is unique because, in most of the cyanobacterial strains, the sn-2 position is esterified exclusively with C16 fatty acids, generally 16:0. Transformation of Synechocystis sp. PCC 6803 with the PCC8801_1274 gene for lysophosphatidic acid acyltransferase (1-acyl sn-glycerol-3-phosphate acyltransferase) from Cyanothece sp. PCC 8801 increased the level of 14:0 from 2% to 17% in total lipids and the increase in the 14:0 content was observed in all lipid classes. These findings suggest that the high content of 14:0 in Cyanothece sp. PCC 8801 might be a result of the high specificity of this acyltransferase toward the 14:0-acyl-carrier protein. PMID- 29793057 TI - Ellagic acid protects from myelin-associated sphingolipid loss in experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalomyelitis (EAE), the most common model for multiple sclerosis, is characterized by inflammatory cell infiltration into the central nervous system and demyelination. Previous studies have demonstrated that administration of some polyphenols may reduce the neurological alterations of EAE. In this work, we show that ellagic acid, a polyphenolic compound, is beneficial in EAE, most likely through stimulation of ceramide biosynthesis within the brain. EAE was induced in Lewis rats by injection of guinea-pig spinal cord tissue along with Freund's complete adjuvant containing Mycobacterium tuberculosis. Clinical signs first appeared at day 8 post-immunization and reached a peak within 3 days, coincident with reduction of myelin basic protein (MBP) in the cortex. Sphingolipids, the other major components of myelin, also decreased at the acute phase of EAE, both in the cerebral cortex and in the spinal cord. In rats receiving ellagic acid in the drinking water from 2 days before immunization, the onset of the disease was delayed and clinical signs were reduced. This amelioration of clinical signs was accompanied by sustained levels of both MBP and sphingolipid in the cortex, without apparent changes in infiltration of inflammatory CD3+ T-cells, microglial activation, or weight loss, which together suggest a neuroprotective effect of ellagic acid. Finally, in glioma and oligodendroglioma cells we demonstrate that urolithins, the ellagic acid metabolites that circulate in plasma, stimulate the synthesis of ceramide. Together these data suggest that ellagic acid consumption protects against demyelination in rats with induced EAE, likely by a mechanism involving sphingolipid synthesis. PMID- 29793061 TI - Microstructural imaging of the human brain with a 'super-scanner': 10 key advantages of ultra-strong gradients for diffusion MRI. AB - The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Delta, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'. PMID- 29793059 TI - Longitudinal surveillance of drug resistance in Plasmodium falciparum isolates from the China-Myanmar border reveals persistent circulation of multidrug resistant parasites. AB - Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007-2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of IC50s. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resistance genetic background. Furthermore, network analysis of drug resistance genes indicated that certain haplotypes associated multidrug resistance persisted in these years, albeit there were year-to-year fluctuations of the predominant haplotypes. PMID- 29793060 TI - A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks. AB - Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 +/- 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging. PMID- 29793058 TI - The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans. AB - Parasitic nematodes infect over 1/4 th of the human population and are a major burden on livestock and crop production. Benzimidazole class anthelmintics are widely used to treat infections, but resistance is a widespread problem. Mutation of genes encoding the benzimidazole target beta-tubulin is a well-established mechanism of resistance, but recent evidence suggests that metabolism of the drugs may also occur. Our objective was to investigate contributions of the detoxification-response transcription factor SKN-1 to anthelmintic drug resistance using C. elegans. We find that skn-1 mutations alter EC50 of the common benzimidazole albendazole in motility assays by 1.5-1.7 fold. We also identify ugt-22 as a detoxification gene associated with SKN-1 that influences albendazole efficacy. Mutation and overexpression of ugt-22 alter albendazole EC50 by 2.3-2.5-fold. The influence of a nematode UGT on albendazole efficacy is consistent with recent studies demonstrating glucose conjugation of benzimidazoles. PMID- 29793062 TI - Functional MRI of brain physiology in aging and neurodegenerative diseases. AB - Brain aging and associated neurodegeneration constitute a major societal challenge as well as one for the neuroimaging community. A full understanding of the physiological mechanisms underlying neurodegeneration still eludes medical researchers, fuelling the development of in vivo neuroimaging markers. Hence it is increasingly recognized that our understanding of neurodegenerative processes likely will depend upon the available information provided by imaging techniques. At the same time, the imaging techniques are often developed in response to the desire to observe certain physiological processes. In this context, functional MRI (fMRI), which has for decades provided information on neuronal activity, has evolved into a large family of techniques well suited for in vivo observations of brain physiology. Given the rapid technical advances in fMRI in recent years, this review aims to summarize the physiological basis of fMRI observations in healthy aging as well as in age-related neurodegeneration. This review focuses on in-vivo human brain imaging studies in this review and on disease features that can be imaged using fMRI methods. In addition to providing detailed literature summaries, this review also discusses future directions in the study of brain physiology using fMRI in the clinical setting. PMID- 29793063 TI - Progressive right ventricular enlargement due to pulmonary regurgitation: Clinical characteristics of a "low-risk" group. AB - BACKGROUND: The optimal interval between serial cardiac magnetic resonance imaging (CMRI) scans for monitoring right ventricular (RV) enlargement in the setting of severe pulmonic valve regurgitation (PR) is unknown. The purposes of this study were to (1) determine the annual change in RV volume on serial CMRI scans and (2) identify the risk factors for rapid progression of RV enlargement. METHODS: A retrospective study of adults with postintervention native valve PR and >=2 CMRI scans at Mayo Clinic Rochester from 2000 to 2015 was conducted. Rapid progression of RV enlargement was defined as first upper quartile of annual increase in RV end-diastolic volume index (RVEDVi) for the cohort. RESULTS: Of the 63 patients (age, 36 +/- 9 years) in the study, 43 (68%) had tetralogy of Fallot, whereas 20 (32%) had valvular pulmonic stenosis. Right ventricular outflow tract interventions that resulted in PR were balloon pulmonary valvuloplasty (n = 4; 7%), transannular patch repair (n = 30; 58%), and nontransannular patch repair (n = 18; 35%). Interval between baseline and second CMRI was 2 (1-4) years. In comparison to baseline CMRI, RVEDVi increased from 130 (109-141) to 135 (126-155) mL/m2 and median annual change in RVEDVi was 3.1 (1.7 5.9) mL/m2. Univariate risk factors for rapid progression of RV enlargement (annual increase in RVEDVi >6 mL/m2) were >=moderate tricuspid regurgitation and RVEDVi >130 mL/m2. Among the 24 patients without these risk factors (low-risk subgroup), RVEDVi increased by only 3 (0-7) mL/m2 over 7 (5-9) years. CONCLUSIONS: Patients with PR without RVEDVi >130 mL/m2 and/or >=moderate tricuspid regurgitation represent a low-risk subgroup that may be appropriate for clinical and echo follow-up but may potentially require infrequent CMRI follow up. PMID- 29793064 TI - Industrial waste as a source of surface and groundwater pollution for more than half a century in a sector of the Rio de la Plata coastal plain (Argentina). AB - Environmental liabilities have become one of the most important problems of the last years, especially those of contaminated sites located in urban areas which have been abandoned by pollution intensive industries. Such sites may contain hazardous materials that pose risks to human health and the environment. Industrial waste from the ancient sulfuric acid industry is scattered in a local area at the petrochemical pole in a sector of the Rio de la Plata coastal plain. The aim of this work is to define the geochemical processes that determine the alteration of waste in the old sulfuric acid industry (OSAI) area and to study the migration of soluble pollutants to groundwater. A survey of soil and waste deposit was carried out and samples were examined by X-ray diffraction, under a scanning electron microscope and a polarizing microscope. Surface water and groundwater samples, both to the unconfined and semi-confined aquifers, were collected to determine electrical conductivity, pH and major elements. The results show the presence of minerals composed of sulfur associated with jarosite and iron oxides on superficial sediments. The detailed study of soil sediments together with that of the water physicochemical characteristics make it possible to understand the geochemical processes developed in soil that cause the high concentrations of sulfates in groundwater. Furthermore, high SO4-2 concentration registered in the semi-confined aquifer due to its infiltration from the unconfined aquifer shows that the industrial pollution has an important impact at local level. These results may contribute to the understanding of chemical processes and pollutants distribution in highly industrialized coastal plain areas. PMID- 29793065 TI - Arsenic removal by As-hyperaccumulator Pteris vittata from two contaminated soils: A 5-year study. AB - The ability of As-hyperaccumulator Pteris vittata to remove As from two contaminated soils (CCA from an As-treated wood facility and DVA from a cattle dipping vat) over 5 years was investigated for the first time. The goal was to evaluate P. vittata's ability to continuously remove As during 10 harvests and identify how soil As was affected by P. vittata under P-sufficient (P-fertilizer) and P-limiting (phosphate rock) conditions. Sequential extraction was used to determine changes in metal distribution among different soil fractions. The high frond biomass production occurred on the 9th (62.1-63.9 and 35.6-63.5 g plant-1) and 10th harvest (58.6-60.7 and 51.9-57.1 g plant-1) for CCA and DVB soils, though frond As concentration decreased. Soil arsenic removal averaged 7-10% per harvest during the 1-6th harvests and was reduced to 0-3% during the 7-10th harvests for DVA and CCA soils. Arsenic from all fractions, excluding the residual fraction, was affected by plant uptake. The largest reduction occurred in the amorphous fraction of CCA-soil at 64-66% (61.2-61.5 to 20.8-21.8 mg kg-1) and in the crystalline fraction of DVA-soil at 50-86% (2.18-4.35 to 0.61-1.10 mg kg-1). Soil As concentrations were reduced by 37-47% from 26.7 to 129 to 15.6 16.8 and 68.9-70.1 mg kg-1 for the DVA and CCA soils, respectively. Our data indicated that P. vittata efficiently solubilized non-labile As under P-limiting conditions without impacting its As depletion. PMID- 29793066 TI - Rapid and effective removal of As(III) and As(V) using spore@Ti4+ microspheres. AB - Removing arsenic from aquatic environments has become an urgent problem worldwide. In this study, Ti4+- loaded bacterial spore were adopted as a novel adsorbent (spore@Ti4+ microspheres) for the adsorption efficient removal of arsenite (As(III)) and arsenate (As(V)). The developed adsorbents were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS). Results indicated that the adsorption kinetics was well described by a pseudo-second-order kinetic model, and the adsorption process rapidly achieved equilibrium within 15 min at pH 7.0. The adsorption mechanism was also investigated. The maximum adsorption capacities for As(III) and As(V) were 97.26 mg g-1 and 137.01 mg g-1, respectively, based on the isothermal studies. These properties suggest that spore@Ti4+ microspheres can be potentially applied in water treatment. PMID- 29793067 TI - Performance and methane fermentation characteristics of a pilot scale anaerobic membrane bioreactor (AnMBR) for treating pharmaceutical wastewater containing m cresol (MC) and iso-propyl alcohol (IPA). AB - In this study, a pilot scale anaerobic membrane bioreactor (AnMBR) was operated for 80 days to treat pharmaceutical wastewater containing m-cresol (MC) and iso propyl alcohol (IPA). The aim of the study is to investigate the performance and methane fermentation characteristics of AnMBR at different hydraulic retention time (HRT) (48, 36, 24, 18 and 12 h). The average total removal efficiencies of MC and IPA were 95%, 96% during the 80 days, which demonstrated that the AnMBR system performed well in the MC and IPA removal. The major volatile fatty acid (VFA) was found to be acetic acid, propionic acid, butyric acid, besides, the VFA accumulated apparently when HRT decreased to 12 h. The decrease of HRT led to an increase of relative abundance of methanosarcina from 13 to 33% and a decrease in biogas yield from 0.19 to 0.05 L/gCODremoval. The biogas production was found to increase dramatically at HRT of 36 h. The trend of methane content kept stable at this stage with the average value of 78.5% which higher than other HRTs. The investigation of methanogen community showed that methanosarcinaceae was always dominant acetoclastic methanogens and methanomicrobiales was the dominant hydrogen utilizers throughout the operational period. When the HRT dropped to 12 h, the growth of the methanosarcinaceae and methanomicrobiales was observed, the amount of the methanosarcinaceae and methanomicrobiales sharply increased. After the overall research, HRT of 36 h was chosen as the most suitable operating condition due to the comprehensively preferable performance and more economical. PMID- 29793068 TI - Prenatal phthalate exposure, birth outcomes and DNA methylation of Alu and LINE-1 repetitive elements: A pilot study in China. AB - BACKGROUND: Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes. OBJECTIVE: To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort. METHODS: Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis. RESULTS: We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2 (ethylhexyl) phthalate (?DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P < 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P < 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes. CONCLUSION: Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood. PMID- 29793070 TI - Intradialytic blood pressure pattern recognition based on density peak clustering. AB - End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD) and requires hemodialysis (HD) for survival. Intradialytic blood pressure (IBP) measurements are necessary to ensure patient safety during HD treatments and have critical clinical and prognostic significance. Studies on IBP measurements, especially IBP patterns, are limited. All related studies have been based on a priori knowledge and artificially classified IBP patterns. Therefore, the results were influenced by subjective concepts. In this study, we proposed a new approach to identify IBP patterns to classify ESRD patients. We used the dynamic time warping (DTW) algorithm to measure the similarity between two series of IBP data. Five blood pressure (BP) patterns were identified by applying the density peak clustering algorithm (DPCA) to the IBP data. To illustrate the association between BP patterns and prognosis, we constructed three random survival forest (RSF) models with different covariates. Model accuracy was improved 3.7-6.3% by the inclusion of BP patterns. The results suggest that BP patterns have critical clinical and prognostic significance regarding the risk of cerebrovascular events. We can also apply this clustering approach to other time series data from electronic health records (EHRs). This work is generalizable to analyses of dense EHR data. PMID- 29793069 TI - A 2D tank test on remediation of nitrobenzene-contaminated aquifer using in-situ reactive zone with emulsified nanoscale zero-valent iron. AB - Nitrobenzene (NB) is one of the most challenging pollutants for groundwater remediation due to its great harm and recalcitrance. Emulsified nanoscale zero valent iron (EZVI) is considered as a promising agent for in-situ remediation of contaminated groundwater for its high reactivity, good durability and low cost. In this paper, 2D tank experiment was conducted to evaluate the effectiveness of enhanced remediation of NB-contaminated groundwater with EZVI. 9 L of EZVI solution was injected into aquifer to establish in-situ reactive zone (IRZ) before 40 d of NB contamination. Results indicate that injection of EZVI leads to 90% reduction of total NB, which is mainly converted to aniline (AN). NB concentration decreases along the flow path in the tank. Fe2+ is generated from Fe0 oxidation. Significant acetate and bicarbonate are released due to emulsified oil decomposition during the whole operation time. Groundwater pH maintains in neutral value (6.6-8.2) owing to the balance between organic acids and OH- released after iron oxidation. Drastic decrease of ORP and DO indicates the transformation from oxidizing to reducing condition, leading to the reduction of oxidative species (e.g. sulfate, nitrate) in subsurface. Calculation of reducing equivalents suggests that microbial breakdown of emulsified oil provides more electrons than Fe0 oxidation does to the system. Both biotic and abiotic processes are involved in the enhanced degradation of NB. PMID- 29793072 TI - Leveraging semantic labels for multi-level abstraction in medical process mining and trace comparison. AB - Many medical information systems record data about the executed process instances in the form of an event log. In this paper, we present a framework, able to convert actions in the event log into higher level concepts, at different levels of abstraction, on the basis of domain knowledge. Abstracted traces are then provided as an input to trace comparison and semantic process discovery. Our abstraction mechanism is able to manage non trivial situations, such as interleaved actions or delays between two actions that abstract to the same concept. Trace comparison resorts to a similarity metric able to take into account abstraction phase penalties, and to deal with quantitative and qualitative temporal constraints in abstracted traces. As for process discovery, we rely on classical algorithms embedded in the framework ProM, made semantic by the capability of abstracting the actions on the basis of their conceptual meaning. The approach has been tested in stroke care, where we adopted abstraction and trace comparison to cluster event logs of different stroke units, to highlight (in)correct behavior, abstracting from details. We also provide process discovery results, showing how the abstraction mechanism allows to obtain stroke process models more easily interpretable by neurologists. PMID- 29793071 TI - Extracting similar terms from multiple EMR-based semantic embeddings to support chart reviews. AB - OBJECTIVE: Word embeddings project semantically similar terms into nearby points in a vector space. When trained on clinical text, these embeddings can be leveraged to improve keyword search and text highlighting. In this paper, we present methods to refine the selection process of similar terms from multiple EMR-based word embeddings, and evaluate their performance quantitatively and qualitatively across multiple chart review tasks. MATERIALS AND METHODS: Word embeddings were trained on each clinical note type in an EMR. These embeddings were then combined, weighted, and truncated to select a refined set of similar terms to be used in keyword search and text highlighting. To evaluate their quality, we measured the similar terms' information retrieval (IR) performance using precision-at-K (P@5, P@10). Additionally a user study evaluated users' search term preferences, while a timing study measured the time to answer a question from a clinical chart. RESULTS: The refined terms outperformed the baseline method's information retrieval performance (e.g., increasing the average P@5 from 0.48 to 0.60). Additionally, the refined terms were preferred by most users, and reduced the average time to answer a question. CONCLUSIONS: Clinical information can be more quickly retrieved and synthesized when using semantically similar term from multiple embeddings. PMID- 29793073 TI - Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy. AB - : The combination of chemotherapy and photothermaltherapy (PTT) via stimuli responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli response controlled drug delivery and combination chemo-photothermal tumor therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy. PMID- 29793074 TI - Cross-linked electrospun cartilage acellular matrix/poly(caprolactone-co-lactide co-glycolide) nanofiber as an antiadhesive barrier. AB - : In this work, we chose cartilage acellular matrix (CAM) as a promising antiadhesive material because CAM effectively inhibits the formation of blood vessels, and we used electrospinning to prepare antiadhesive barriers. Additionally, we synthesized N-hydroxysuccinimide (NHS)-poly(caprolactone-co lactide-co-glycolide)-NHS (MP) copolymers (to tune degradation) as a cross linking agent for CAM. This is the first report on the development of electrospun cross-linked (Cx) CAM/MP (CA/P) nanofiber (NF) (Cx-CA/P-NF) with a tunable degradation period as an antiadhesive barrier. Compared with the CA/P-NF before cross-linking, the electrospun Cx-CA/P-NF after cross-linking showed different biodegradation. Cx-CA/P-NF significantly inhibited the in vitro attachment and proliferation of human umbilical vein endothelial cells (HUVECs), as confirmed by an MTT assay and scanning electron microscopy images. Cx-CA/P-NFs implanted between a surgically damaged peritoneal wall and cecum gradually degraded in 7 days; this process was monitored by NIR imaging. The in vivo evaluation of the anti-tissue adhesive effect of Cx-CA/P-NFs revealed little adhesion, few blood vessels, and negligible inflammation at 7 days determined by hematoxylin and eosin staining. ED1 staining of Cx-CA/P-NFs showed infiltration of few macrophages because of the inflammatory response to the Cx-CA/P-NF as compared with an untreated injury model. Additionally, Cx-CA/P-NFs significantly suppressed the formation of blood vessels between the peritoneal wall and cecum, according to CD31 staining. Overall, Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Thus, it is reasonable to conclude that the Cx-CA/P-NF designed herein successfully works as an antiadhesive barrier with a tunable degradation period. STATEMENT OF SIGNIFICANCE: The cartilage acellular matrix (CAM) can inhibit the formation of fibrous tissue bridges and blood vessels between the tissue at an injured site and the surrounding healthy tissues. However, CAM has not been rigorously investigated as an antiadhesive barrier. In this manuscript, the cross-linked CAM nanofiber (Cx-CA/P-NF) designed herein successfully works as an antiadhesive barrier. Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Moreover, we demonstrated the suitable properties of Cx-CA/P-NF such as easy cross-linking by maintaining the antiadhesive properties, controllable biodegradation, and in vivo antiadhesive effect of Cx-CA/P-NF. PMID- 29793075 TI - Newcastle disease virus induces G0/G1 cell cycle arrest in asynchronously growing cells. AB - The cell cycle, as a basic cellular process, is conservatively regulated. Consequently, subversion of the host cell replication cycle is a common strategy employed by many viruses to create a cellular environment favorable for viral replication. Newcastle disease virus (NDV) causes disease in poultry and is also an effective oncolytic agent. However, the effects of NDV infection on cell cycle progression are unknown. In this study, we showed that NDV replication in asynchronized cells resulted in the accumulation of infected cells in the G0/G1 phase of the cell cycle, which benefitted the proliferation of NDV. Examination of various cell cycle-regulatory proteins showed that expression of cyclin D1, was significantly reduced following NDV infection. Importantly, the decreased expression of cyclin D1 was reversed by inhibition of CHOP expression, indicating that induction of the PERK-eIF-2a-ATF4-CHOP signaling pathway was involved in the G0/G1 phase cell cycle arrest observed following NDV infection. PMID- 29793076 TI - Porcine circovirus type 2 inhibits inter-beta expression by targeting Karyopherin alpha-3 in PK-15 cells. AB - Interferon (IFN)-mediated antiviral response is an important part of host defense. Previous studies reported that porcine circovirus type 2 (PCV2) inhibits interferon production, but the mechanism is still poorly understood. In this study, PCV2 suppresses IFN-beta and IRF3 promoters and mRNA level of IFN-beta induced by ISD or Poly(I:C), but has no effect on the activation of AP-1 and NF kappaB. Furthermore, PCV2 decreases the mRNA level of IFN-beta and IFN-beta promoter activity driven by STING, TBK1, IRF3, and IRF3/5D, and causes a reduction in the protein level of nuclear p-IRF3. In addition, PCV2 interrupts the interaction of KPNA3, rather than KPNA4, with p-IRF3. Overexpression of KPNA3 restores IFN-beta promoter activity. These results indicate that PCV2 disrupts the interaction of KPNA3 with p-IRF3 and blocks p-IRF3 translocation to the nucleus, thereby inhibiting IFN-beta induction in PK-15 cells. PMID- 29793077 TI - fMRI classification method with multiple feature fusion based on minimum spanning tree analysis. AB - Resting state functional brain networks have been widely studied in brain disease research. Conventional network analysis methods are hampered by differences in network size, density and normalization. Minimum spanning tree (MST) analysis has been recently suggested to ameliorate these limitations. Moreover, common MST analysis methods involve calculating quantifiable attributes and selecting these attributes as features in the classification. However, a disadvantage of these methods is that information about the topology of the network is not fully considered, limiting further improvement of classification performance. To address this issue, we propose a novel method combining brain region and subgraph features for classification, utilizing two feature types to quantify two properties of the network. We experimentally validated our proposed method using a major depressive disorder (MDD) patient dataset. The results indicated that MSTs of MDD patients were more similar to random networks and exhibited significant differences in certain regions involved in the limbic-cortical striatal-pallidal-thalamic (LCSPT) circuit, which is considered to be a major pathological circuit of depression. Moreover, we demonstrated that this novel classification method could effectively improve classification accuracy and provide better interpretability. Overall, the current study demonstrated that different forms of feature representation provide complementary information. PMID- 29793078 TI - Comparison of performance-based assessment and real world skill in people with serious mental illness: Ecological validity of the Test of Grocery Shopping Skills. AB - Valid functional measures are essential for clinical and research efforts that address recovery and community functioning in people with serious mental illness. Although there is a great deal of interest in functional assessment, there is limited research supporting how well current evaluation methods provide a true assessment of real world functioning or naturalistic behavior. To address this gap in the literature, the present study examined the performance of individuals with serious mental illness (i.e., diagnosis of schizophrenia-spectrum, bipolar disorder, or other depression/anxiety diagnoses and accompanying functional disability) on the Test of Grocery Shopping Skills (TOGSS), a performance-based naturalistic task. We compared TOGSS performance to two dimensions of real world functioning: directly observed real world grocery shopping and ratings of community functioning. Results indicated that the TOGSS was significantly associated with real life grocery shopping, in terms of both shopping accuracy (r = 0.424) and time (r = 0.491). Further, self-report and observer-rated methods of assessing real world shopping behaviors were significantly correlated (r = 0.455). To our knowledge, this is one of the first studies to directly compare a performance-based naturalistic skill assessment with carefully observed real world performance of that skill in people with serious mental illness. These findings support the feasibility and ecological validity of performance-based naturalistic assessment with the TOGSS. PMID- 29793079 TI - Shifts in wind energy potential following land-use driven vegetation dynamics in complex terrain. AB - Many mountainous regions with high wind energy potential are characterized by multi-scale variabilities of vegetation in both spatial and time dimensions, which strongly affect the spatial distribution of wind resource and its time evolution. To this end, we developed a coupled interdisciplinary modeling framework capable of assessing the shifts in wind energy potential following land use driven vegetation dynamics in complex mountain terrain. It was applied to a case study area in the Romanian Carpathians. The results show that the overall shifts in wind energy potential following the changes of vegetation pattern due to different land-use policies can be dramatic. This suggests that the planning of wind energy project should be integrated with the land-use planning at a specific site to ensure that the expected energy production of the planned wind farm can be reached over its entire lifetime. Moreover, the changes in the spatial distribution of wind and turbulence under different scenarios of land-use are complex, and they must be taken into account in the micro-siting of wind turbines to maximize wind energy production and minimize fatigue loads (and associated maintenance costs). The proposed new modeling framework offers, for the first time, a powerful tool for assessing long-term variability in local wind energy potential that emerges from land-use change driven vegetation dynamics over complex terrain. Following a previously unexplored pathway of cause-effect relationships, it demonstrates a new linkage of agro- and forest policies in landscape development with an ultimate trade-off between renewable energy production and biodiversity targets. Moreover, it can be extended to study the potential effects of micro-climatic changes associated with wind farms on vegetation development (growth and patterning), which could in turn have a long term feedback effect on wind resource distribution in mountainous regions. PMID- 29793080 TI - Visualizing the shape of society: An analysis of public bads and burden allocation due to household consumption using an input-output approach. AB - This study investigates how our lifestyles can cause societal issue including a reduction in social equity due to the consumption of natural resources. Based on a range of household environmental footprints and their application to a quantitative social equity evaluation framework, a methodology is proposed which identifies the creation and origin of public bads within society. This research builds on the methodologies of energy policy sustainability evaluation incorporated with environmentally extended input output analysis in order to critically assess lifestyle-based consumption impacts, and to quantify the allocation of subsequent burdens across generations. Further, the proposed methodology is applied to a case study in Japan, an aging, shrinking population. Analysis identifies the increasing burden originating with elderly generations, and due to the resolution offered by the methodology, specifically identifies commodities and services which underpin these future burdens, allowing for policy implications to be drawn. The public bads and consumption burden indicator established through the described methodology is proposed as a footprint harmonizing tool to assess sustainability and supplement the footprint family. PMID- 29793081 TI - Geochemical anomalies of trace elements in unremediated soils of Mt. Karczowka, a historic lead mining area in the city of Kielce, Poland. AB - Concentrations of selected trace elements (Ag, As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Zn) and rare earth elements were determined in 61 samples of surface soils collected from Mt. Karczowka, a historic Pb ore mining area located in the city of Kielce, south-central Poland. Some of these samples were subjected to XRD analyses and Pb stable isotope measurements. The mineral and chemical composition of rock samples were also examined. Mining activity in the study area was conducted mostly during 15th-17th centuries using technologically primitive methods, and was finally ceased in the first half of the 19th century. More than three thousand old shafts, pits and adits occur in the study area and its vicinity. The soils of the study area have not been remediated since the end of the mining operations. The trace elements of the examined surface soils are heterogeneously distributed with lead concentrations in the range of 41-9114 mg/kg and Pb isotopic signatures similar to those of local galena. The results of trace element measurements allowed us to discriminate geochemical anomalies from background levels and to link mineralogy of the host rocks to the origin of anomalous element concentrations. This study shows that elevated levels of elements of geogenic origin have remained in surface soil for two centuries after cessation of mining operations. PMID- 29793083 TI - Optimization adsorption of norfloxacin onto polydopamine microspheres from aqueous solution: Kinetic, equilibrium and adsorption mechanism studies. AB - Polydopamine microspheres (PDMPs) synthesized by a facile solution oxidation method were adopted as a potential adsorbent for the removal of Norfloxacin (NOR) from aqueous solution. The morphologies and properties of PDMPs were characterized using TEM, SEM, FTIR and pHPZC. Parameters effects such as contact time, initial pH, initial concentration and ionic strength on the adsorption capacity of NOR onto PDMPs were studied. To maximize NOR removal from liquid phase, Box-Behnken experimental design (BBD) combined with response surface modeling (RSM) was employed based on the 17 preliminary experiments at 308 K. Optimum contact time, initial NOR concentration and initial pH value were found to be 97 min, 303 mg.L-1 and 6.6, respectively, the corresponding NOR removal capacity was found to be 307 mg.g-1. Batch adsorption experiments under the optimal conditions were conducted to investigate kinetics, thermodynamics and adsorption isotherm. Kinetic analysis confirmed that the kinetic data were well described by Pseudo-second order model. The experimental equilibrium data were well fitted by Langmuir, Redlich-Peterson, Koble-Corrigan and Dubinin Radushkevich models. Thermodynamic parameters such as Gibbs free energy, enthalpy and entropy were calculated and the results indicated that the NOR adsorption onto PDMPs was spontaneous and endothermic. The adsorption process may be attributed to the electrostatic interaction, the formation of hydrogen bonds or pi-pi stacking interactions among the polydopamine (PDA) and NOR molecule. PMID- 29793082 TI - Atmospheric impacts of a natural gas development within the urban context of Morgantown, West Virginia. AB - The Marcellus Shale Energy and Environment Laboratory (MSEEL) in West Virginia provides a unique opportunity in the field of unconventional energy research. By studying near-surface atmospheric chemistry over several phases of a hydraulic fracturing event, the project will help evaluate the impact of current practices, as well as new techniques and mitigation technologies. A total of 10 mobile surveys covering a distance of approximately 1500 km were conducted through Morgantown. Our surveying technique involved using a vehicle-mounted Los Gatos Research gas analyzer to provide geo-located measurements of methane (CH4) and carbon dioxide (CO2). The ratios of super-ambient concentrations of CO2 and CH4 were used to separate well-pad emissions from the natural background concentrations over the various stages of well-pad development, as well as for comparisons to other urban sources of CH4. We found that regional background methane concentrations were elevated in all surveys, with a mean concentration of 2.699 +/- 0.006 ppmv, which simply reflected the complexity of this riverine urban location. Emissions at the site were the greatest during the flow-back phase, with an estimated CH4 volume output of 20.62 +/- 7.07 g/s, which was significantly higher than other identified urban emitters. Our study was able to successfully identify and quantify MSEEL emissions within this complex urban environment. PMID- 29793085 TI - Socio-demographic factors associated with choosing violent methods of suicide, 2011-2016, Ilam province. AB - BACKGROUND: In new strategies towards of suicide prevention the best approach currently is based on specific method had specific risk factors. Therefore in this study we aimed to find out the association between socio-demographic factors and methods in completed suicide, 2011-2016, Ilam province. METHODS: A cross sectional study, 2011-2016, was conducted. A total of 540 completed suicides were recruited to the study. Data were collected by systematic registration suicide data (SRSD) and Legal Medicine Organization (LMO). After performs of descriptive statistics, to analysis of effects of each independent variable to the methods Multinomial Logistic Regression (MLR) was used, also adjusted odds ratio (AOR) was used to reporting of associations. RESULTS: According to the result (55.8%) of deaths were occurred by hanging and self-immolation also a majority of suicides were occurred in females (60%). The important methods in males and females were hanging (70.6%) and self-immolation (72.8%), respectively. The self immolation vs. others was significantly higher in cases that have mental disorders (AOR) = 2.05, 95% CI: 1.11, 3.78); also in cases with financial problem (AOR) = 2.70, 95% CI: 1.28, 5.71). CONCLUSION: According to the finding age groups, gender, marital status, residence, and mental disorders are the important risk factors that effects on choosing of methods. Therefore consideration of this excess risk by this mentioned factors in prevention programs can be reducing the risk of death from suicide in society. PMID- 29793084 TI - Subthreshold depression among diabetes patients in Beijing: Cross-sectional associations among sociodemographic, clinical, and behavior factors. AB - BACKGROUND: This study explores the prevalence of subthreshold depression (SubD) and its association with factors in type 2 diabetes mellitus (T2DM) patients. METHODS: This cross-sectional study involved 808 outpatients with T2DM from ten hospitals in Beijing between September 2015 and January 2016. All participants completed the Patient Health Questionnaire 9-item (PHQ-9) to evaluate depressive status, with scores between 5 and 14 considered SubD. Conditional logistic regression was conducted to investigate the variables associated with SubD in T2DM patients. RESULTS: T2DM patients with SubD comprised 11.6% (n = 94) of the sample. The odd ratios for the variables having significant positive associations with SubD were: being a women (OR = 1.90; 95%CI: 1.09-3.32), divorced/widowed (OR = 3.27; 95%CI: 1.46-7.30), comorbidity of cerebrovascular disease (OR = 2.00; 95%CI: 1.06-3.76), more diabetic complications (OR = 8.04; 95%CI: 2.77-23.31), and higher HbA1c in men (OR = 2.41; 95%CI: 1.25-4.64). Being older (OR = 0.78; 95%CI: 0.62-0.98), exercising more (OR = 0.44; 95%CI: 0.22-0.91) and poverty (OR = 0.36; 95%CI: 0.19-0.69) were negatively related to SubD. LIMITATIONS: The sample was mainly recruited from hospital settings, which limits generalization. The study's cross-sectional design precludes making causal inferences. CONCLUSIONS: The proportion of SubD was estimated to be 11.6% among T2DM patients in Beijing. Having more diabetic complications and being divorced/widowed made the odds of having SubD 8-fold and 3-fold higher than not having it, respectively. The relationship between SubD and diabetes necessitates early screening for milder forms of depression, which can alleviate the social burden and individual impairment from major depression or other chronic diseases. PMID- 29793086 TI - Challenges in identifying cognitive assessment tools prior to validation studies. PMID- 29793088 TI - Decellularized and matured esophageal scaffold for circumferential esophagus replacement: Proof of concept in a pig model. AB - Surgical resection of the esophagus requires sacrificing a long portion of it. Its replacement by the demanding gastric pull-up or colonic interposition techniques may be avoided by using short biologic scaffolds composed of decellularized matrix (DM). The aim of this study was to prepare, characterize, and assess the in vivo remodeling of DM and its clinical impact in a preclinical model. A dynamic chemical and enzymatic decellularization protocol of porcine esophagus was set up and optimized. The resulting DM was mechanically and biologically characterized by DNA quantification, histology, and histomorphometry techniques. Then, in vitro and in vivo tests were performed, such as DM recellularization with human or porcine adipose-derived stem cells, or porcine stromal vascular fraction, and maturation in rat omentum. Finally, the DM, matured or not, was implanted as a 5-cm-long esophagus substitute in an esophagectomized pig model. The developed protocol for esophageal DM fulfilled previously established criteria of decellularization and resulted in a scaffold that maintained important biologic components and an ultrastructure consistent with a basement membrane complex. In vivo implantation was compatible with life without major clinical complications. The DM's scaffold in vitro characteristics and in vivo implantation showed a pattern of constructive remodeling mimicking major native esophageal characteristics. PMID- 29793087 TI - Skin Allografting Activates Anti-tumor Immunity and Suppresses Growth of Colon Cancer in Mice. AB - INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b) donors to BALB/c (H-2d) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 * 106 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation. RESULTS: The results showed that as compared to non transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11c+MHC-classII+CD86+ DCs, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, as well as decreased percentage of CD4+CD25+Foxp3+ T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were significantly higher within the tumor in skin transplant groups than that in non-transplant group. CONCLUSIONS: Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment. PMID- 29793089 TI - Gold and gold-silver alloy nanoparticles enhance the myogenic differentiation of myoblasts through p38 MAPK signaling pathway and promote in vivo skeletal muscle regeneration. AB - Under the severe trauma condition, the skeletal muscles regeneration process is inhibited by forming fibrous scar tissues. Understanding the interaction between bioactive nanomaterials and myoblasts perhaps has important effect on the enhanced skeletal muscle tissue regeneration. Herein, we investigate the effect of monodispersed gold and gold-silver nanoparticles (AuNPs and Au-AgNPs) on the proliferation, myogenic differentiation and associated molecular mechanism of myoblasts (C2C12), as well as the in vivo skeletal muscle tissue regeneration. Our results showed that AuNPs and Au-AgNPs could support myoblast attachment and proliferation with negligible cytotoxicity. Under various incubation conditions (normal and differentiation medium), AuNPs and Au-AuNPs significantly enhanced the myogenic differentiation of myoblasts by upregulating the expressions of myosin heavy chain (MHC) protein and myogenic genes (MyoD, MyoG and Tnnt-1). The further analysis demonstrated that AuNPs and Au-AgNPs could activate the p38alpha mitogen-activated protein kinase pathway (p38alpha MAPK) signaling pathway and enhance the myogenic differentiation. Additionally, the AuNPs and Au-AgNPs significantly promote the in vivo skeletal muscle regeneration in a tibialis anterior muscle defect model of rat. This study may provide a nanomaterials-based strategy to improve the skeletal muscle repair and regeneration. PMID- 29793090 TI - Anti-haemostatic compounds from the vampire snail Cumia reticulata: Molecular cloning and in-silico structure-function analysis. AB - Blood-feeding animals are known for their ability to produce bioactive compounds to impair haemostasis and suppress pain perception in the host. These compounds are extremely appealing for pharmacological development since they are generally very effective and specific for their molecular target. A preliminary RNA-Seq based characterization of the secretion from salivary and mid-oesophageal tissues of the vampire snail Cumia reticulata, revealed a complex mixture of feeding related transcripts with potential anaesthetic and anticoagulant action. Based on the cloned full-length mRNAs, it was possible to verify the sequence of five genes encoding haematophagy-related products. The in silico modelled three dimensional structure of each translational product was analysed to gain information on their potential biochemical activity. We have hereby validated and further investigated the assembled transcripts presumably involved in the antihaemostatic action, to improve our comprehensive understanding of this subset of the feeding secretion. The studied proteins included both inhibitors of primary haemostasis such as the vWFA domain-containing proteins, and compounds targeting different steps of the coagulation cascade, as e.g. the Turripeptide like/protease inhibitor, the TFPI-like multiple Kunitz-type protease inhibitors, the Meprin-like metalloproteases and the Astacin/ShKT-like domain-containing proteins. All these molecules showed promising potential for pharmacological development. PMID- 29793091 TI - Effects of surface modification of As2O3-loaded PLGA nanoparticles on its anti liver cancer ability: An in vitro and in vivo study. AB - As2O3-loaded nanoparticles (NPs) based on poly (lactic-co-glycolic acid) (PLGA) were prepared by double emulsion-solvent evaporation method. Then Lactose acid (LA) and/or PEG were modified onto the NPs by chemical covalent coupling through NH2 and -COOH. The FTIR results showed that LA and PEG could be successfully modified onto the surface of the NPs. All the As2O3-loaded PLGA NPs (As2O3@PLGA NPs) presented suitable physical stability, favorable size, and spherical shape. The in vitro release rate of As2O3 from the NPs depended on the surface of the NPs. As expected, the As2O3@PLGA-PEG/LA NPs showed a moderate release rate, the highest anticancer effects and cellular internalization against SMMC-7721 cell line. The PLGA-PEG/LA NPs could represent an effective nano-size delivery system of As2O3 for treatment of liver cancer. PMID- 29793093 TI - Graphene oxide-assisted Au nanoparticle strip biosensor based on GR-5 DNAzyme for rapid lead ion detection. AB - This study has reported that a GR-5 DNAzyme based lead ion strip biosensor could exhibit an enhanced specificity with the assistance of graphene oxide (GO). This enhancement results from the specific pi-stacking interaction between the ribose rings of the nucleobases and the carbon hexagons in GO which can reduce the false positive interference by removing unhybridized ssDNA during the annealing of GR-5 DNAzyme. Meanwhile, conjugate pad was sprayed with two kinds of AuNP-DNA probes, and nitrocellulose membrane test zone and control zone were immobilized with two kinds of biotin-DNA probes, respectively. The limit of detection of this strip biosensor was estimated to be about 0.05 nM (S/N = 3) and 1 nM (with naked eyes) with a linear range from 0.01 to 100 MUM. Furthermore, the strip biosensor exhibited excellent selectivity toward Pb2+ in the presence of other divalent metal ions. For real soil samples, the obtained recoveries were in the range from 91.5% to 113.1%. PMID- 29793092 TI - A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids. AB - Investigating lipid ion pair formation is important for understanding the mechanisms of lipid-mediated drug resistance in bacteria. In this study we have used the charged amphiphiles dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyldimethylammonium bromide (DHDAB), as a model to evaluate the formation of ion pairs by a combined Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis. FTIR was employed to study the environment of the DPPC headgroup phosphate and lipid/surfactant alkane chains, in vesicles formed by the two amphiphiles mixed in various molar ratios. An increase of the absorbance ratio of 1221-1201 cm-1 in the asymmetric phosphate stretching mode was found to follow a sigmoidal relationship with the proportion of DHDAB, increasing to a plateau above a DPPG/DHDAB 1:1 molar ratio of, providing evidence that the PG headgroup phosphate is involved in ion pairing. A consistent red shift was measured for the position of the symmetric CH2 stretch band for the lipid/surfactant 1:1 molar ratio mixture, which is indicative of an increased ordering of the hydrophobic chains. The DSC experiments yielded information about the thermotropic and the mixing behaviour of the lipid/surfactant systems. DPPG and DHDAB seem to form an ion pair with cluster compound characteristics at the equimolar ratio. Most interestingly, the DPPG/DHDAB 2:1 molar ratio mixture is characterized by strong intermolecular interactions, which result in a pronounced stabilization of the gel phase, possibly through the formation of a closely-associated ion triplet configuration in which the charges are delocalised across the headgroups. PMID- 29793094 TI - Effects of chronic antipsychotic drug exposure on the expression of Translocator Protein and inflammatory markers in rat adipose tissue. AB - The precise effect of antipsychotic drugs on either central or peripheral inflammation remains unclear. An important issue in this debate is to what extent the known peripheral metabolic effects of antipsychotics, including increased adiposity, may contribute to increased inflammation. Adipose tissue is known to contribute to the development of systemic inflammation, which can eventually lead to insulin resistance and metabolic dysregulation. As a first step to address this question, we evaluated whether chronic exposure to clinically comparable doses of haloperidol or olanzapine resulted in the immune activation of rat adipose tissue. Samples of visceral adipose tissue were sampled from male Sprague Dawley rats exposed to, haloperidol, olanzapine or vehicle (all n = 8), for 8 weeks. From these we measured a cytokine profile, protein expression of F4/80 (a phenotypic macrophage marker) and translocator protein (TSPO), a target for radiotracers putatively indicating microgliosis in clinical neuroimaging studies. Chronic olanzapine exposure resulted in significantly higher adipose IL-6 levels compared with vehicle-controls (ANOVA p = 0.008, Bonferroni post-hoc test p = 0.006); in parallel, animals exposed to olanzapine had significantly higher F4/80 expression when compared with vehicle-controls (Mann Whitney Test, p = 0.014), whereas there was no difference between haloperidol and vehicle groups (Mann Whitney test, p = 0.1). There were no significant effects of either drug on adipose TSPO protein levels. Nevertheless, we found a positive correlation between F4/80 and TSPO adipose protein levels in the olanzapine-exposed rats (Spearman's rho = 0.76, p = 0.037). Our data suggest that chronic exposure to olanzapine, but not haloperidol, increases production of the pro-inflammatory cytokine IL-6 in adipose tissue and increased macrophages expression (F4/80), in the absence of measurable changes in TSPO with respect to vehicle. This may have potentially important consequences in terms of metabolic dysregulation associated with long-term antipsychotic treatment. PMID- 29793095 TI - Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models. AB - BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp 3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. PMID- 29793096 TI - Segmentation of histological images and fibrosis identification with a convolutional neural network. AB - Segmentation of histological images is one of the most crucial tasks for many biomedical analyses involving quantification of certain tissue types, such as fibrosis via Masson's trichrome staining. However, challenges are posed by the high variability and complexity of structural features in such images, in addition to imaging artifacts. Further, the conventional approach of manual thresholding is labor-intensive, and highly sensitive to inter- and intra-image intensity variations. An accurate and robust automated segmentation method is of high interest. We propose and evaluate an elegant convolutional neural network (CNN) designed for segmentation of histological images, particularly those with Masson's trichrome stain. The network comprises 11 successive convolutional - rectified linear unit - batch normalization layers. It outperformed state-of-the art CNNs on a dataset of cardiac histological images (labeling fibrosis, myocytes, and background) with a Dice similarity coefficient of 0.947. With 100 times fewer (only 300,000) trainable parameters than the state-of-the-art, our CNN is less susceptible to overfitting, and is efficient. Additionally, it retains image resolution from input to output, captures fine-grained details, and can be trained end-to-end smoothly. To the best of our knowledge, this is the first deep CNN tailored to the problem of concern, and may potentially be extended to solve similar segmentation tasks to facilitate investigations into pathology and clinical treatment. PMID- 29793097 TI - Quantitative assessment of placental perfusion by three-dimensional power Doppler ultrasound for twins with selective intrauterine growth restriction in one twin. AB - OBJECTIVE: We quantitatively assessed placental perfusion using three-dimensional (3D) power Doppler ultrasound for twins with selective intrauterine growth restriction (sIUGR) in one twin. STUDY DESIGN: A prospective cross-sectional study was performed for 104 normal monochorionic diamniotic twins and 30 twins with sIUGR. Twins with sIUGR were divided into two groups: in group I (19 twins), both fetuses had continuous forward end-diastolic blood flow in the umbilical artery; in group II (11 twins), the smaller fetus had a loss or a reverse end diastolic blood flow in the umbilical artery, but the larger fetus had continuous forward end-diastolic blood flow. Volume data of the placenta was acquired in each twin at the plane where the umbilical cord entered the placenta by 3D power Doppler ultrasound, and imaging software was used to calculate the placental vascularization index (VI), flow index (FI), and vascularization flow index (VFI). RESULTS: Among smaller fetuses, the sIUGR and control groups showed significant differences in VI and VFI, as well as significant differences between sIUGR group II and control group in FI. No such differences in placental perfusion were found among larger fetuses. CONCLUSIONS: 3D power Doppler ultrasound could sensitively display the varying degrees of changes in placental perfusion, which could be used for clinical monitoring of placental perfusion in sIUGR twins. PMID- 29793099 TI - Carbon monoxide analysis method in human blood by Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS): Relevance for postmortem poisoning diagnosis. AB - Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 MUmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 MUmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings. PMID- 29793098 TI - Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships. AB - The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti inflammatory properties of RCE. The spectrum-effect relationships between chemical fingerprints and the analgesic and anti-inflammatory effects of RCE were established by gray correlation analysis. UPLC-ESI-MS was used to identify the structures of potential active components, by reference standards comparison. The results showed that a close correlation existed between chemical fingerprints with analgesic and anti-inflammatory activities, and alizarin, 6-hydroxyrubiadin, purpurin and rubiadin might be the active constituents of RCE. In addition, RCE attenuated pathological changes in adjuvant-induced arthritis. The current findings provide a strong basis for combining chemical fingerprints with analgesic and anti-inflammatory activities in assessing the spectrum-effect relationships of RCE. PMID- 29793101 TI - "Survey of Wellbeing of Young Children (SWYC)": how does it fit for screening developmental delay in Brazilian children aged 4 to 58 months? AB - OBJECTIVE: To replicate the original normative study of the SWYC's Milestones Questionnaires for children in Brazil. Our goals were to compare the performance of Brazilian and North American children using this screening tool and to verify the reliability and validity of the Brazilian version. STUDY DESIGN AND SETTING: Cross-sectional study with children aged 1-65 months and their guardians, recruited in southern Brazil. Parents were interviewed using the Developmental Milestones questionnaire, which contains 10 questions about cognitive, motor, social, and language abilities. Item response theory was used to examine item validity. RESULTS: We interviewed 415 parents. SWYC provided the most information on the children's development between 10 and 30 months. The performance of Brazilian and North American children was quite similar when children are younger than 36 months old. Above 36 months, North American children performed almost all items earlier than Brazilians. Convergent validity was 0.73 and internal consistency 0.97. CONCLUSION: The Brazilian version of the Developmental Milestones questionnaire presented acceptable measurement qualities that support the SWYCs potential as a developmental screening tool. As we found important differences between North American and Brazilian children in achieving the milestones, especially among the oldest children, additional normative studies are needed. PMID- 29793100 TI - The still uncertain identity of the channel-forming unit(s) of the mitochondrial permeability transition pore. AB - Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against putative channel-forming components of the MPT pore. We conclude that the structure of the MPT pore still remains largely undefined and suggest that future studies should follow established technical considerations to unambiguously consolidate the channel forming constituent(s) of the MPT pore. PMID- 29793102 TI - Joint attention in Down syndrome: A meta-analysis. AB - BACKGROUND: Some studies have indicated that joint attention may be a relative strength in Down syndrome (DS), but other studies have not. AIM: To conduct a meta-analysis of joint attention in DS to more conclusively determine if this is a relative strength or weakness when compared to children with typical development (TD), developmental disabilities (DD), and autism spectrum disorder (ASD). METHODS AND PROCEDURES: Journal articles published before September 13, 2016, were identified by using the search terms "Down syndrome" and "joint attention" or "coordinating attention". Identified studies were reviewed and coded for inclusion criteria, descriptive information, and outcome variables. OUTCOMES AND RESULTS: Eleven studies (553 participants) met inclusion criteria. Children with DS showed similar joint attention as TD children and higher joint attention than children with DD and ASD. Meta-regression revealed a significant association between age and joint attention effect sizes in the DS vs. TD contrast. CONCLUSIONS AND IMPLICATIONS: Joint attention appears to not be a weakness for children with DS, but may be commensurate with developmental level. Joint attention may be a relative strength in comparison to other skills associated with the DS behavioral phenotype. Early interventions for children with DS may benefit from leveraging joint attention skills. PMID- 29793103 TI - Disruption of the gonadal endocannabinoid system in zebrafish exposed to diisononyl phthalate. AB - DiNP (Di-isononyl phthalate) has been recently introduced as DEHP (Bis (2 ethylhexyl) phthalate) substitute and due to its chemical properties, DiNP is commonly used in a large variety of plastic items. The endocannabinoid system (ECS) is a lipid signaling system involved in a plethora of physiological pathways including the control of the reproductive and metabolic processes. In this study, the effects of DiNP on the ECS of zebrafish (male and female) gonads were analyzed. Adult zebrafish were chronically exposed for 21 days via water to 3 environmentally relevant concentrations of DiNP (42 MUg/L; 4.2 MUg/L; 0.42 MUg/L). In females, the Gonadosomatic Index (GSI) and the number of fertilized eggs were reduced by the lowest concentration of DiNP tested. The levels of two endocannabinoids, Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG), were not affected, while a reduction of the N-oleoyl-ethanolamine (OEA) level was observed. Transcriptional changes were reported in relation to genes coding for the ECS receptors and the enzymes involved in the ECS pathway. DiNP exposure in males reduced the GSI as well as changed the levels of endocannabinoids. Moreover, DiNP treatment induced significative changes in the genes coding for the ECS receptors and enzymes, and significantly increased the activity of the fatty acid amide hydrolase (FAAH). In summary, in zebrafish, exposure to environmentally relevant concentrations of DiNP disrupted the ECS and affected reproduction in a gender specific manner. PMID- 29793105 TI - COPD rat model is more susceptible to cold stress and PM2.5 exposure and the underlying mechanism. AB - The purpose of this study is to verify the hypothesis that chronic obstructive pulmonary disease (COPD) model rat is more susceptible to cold stress and fine particulate matter (PM2.5) exposure than the healthy rat, and explore the related mechanism. COPD rat model, established with cigarette smoke and lipopolysaccharide intratracheal instillation, were exposed to cold stress (0 degrees C) and PM2.5 (0, 3.2, 12.8 mg/ml). After that, the levels of superoxide dismutase, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1) and angiotensin II (Ang-II) in lung were measured, as well as the expression levels of lung 8-hydroxy-2 deoxyguanosine (8-OHdG), nuclear factor kappa B (NF-kappaB), heme-oxygenase-1 (HO 1) and nuclear factor erythroid-2-related factor 2 (Nrf2). There were significant positive relationships between PM2.5 and lung level of iNOS, TNF-alpha, MCP-1 and Ang-II, lung function and pathologic damage in COPD rats. The HO-1, NF-kappaB and 8-OHdG were found highly expressed in COPD rat lung, particularly at the higher PM2.5 dose of cold stress groups, while Nrf2 was found declined. Thus, COPD rats may be more susceptible to cold stress and PM2.5 exposure. Cold stress may aggravate PM2.5-induced toxic effects in the lung of COPD rats through increasing Ang-II/NF-kappaB signaling pathway and suppressing Nrf2 signaling pathway. PMID- 29793104 TI - Uptake, elimination and biotransformation of N-ethyl perfluorooctane sulfonamide (N-EtFOSA) by the earthworms (Eisenia fetida) after in vivo and in vitro exposure. AB - N-ethyl perfluorooctane sulfonamide (N-EtFOSA) is commonly known as the active ingredient of sulfluramid. It can be degraded to perfluorooctane sulfonic acid (PFOS) in biota and environment. Earthworms (Eisenia fetida) were exposed with N EtFOSA to examine the bioaccumulation, elimination and metabolism of N-EtFOSA by the earthworms after in vivo and in vitro exposure. N-EtFOSA could be biodegraded in quartz sands to perfluorooctane sulfonamide (FOSA) and PFOS. In the in vivo tests, in addition to parent N-EtFOSA, three metabolites, including perfluorooctane sulfonamide acetate (FOSAA), FOSA and PFOS also accumulated in earthworms as a result of N-EtFOSA biotransformation, with FOSA as the predominant metabolite. The bioaccumulation factor (BAF) and uptake rate coefficient (ku) of N-EtFOSA from sand were 20.4 and 2.41.d-1, respectively. The elimination rate constants (ke) decreased in the order FOSAA (0.130.d-1) > N EtFOSA (0.118.d-1) > FOSA (0.073.d-1) > PFOS (0.051.d-1). The biotransformation of N-EtFOSA in earthworm was further confirmed by the in vitro test involving incubation of earthworm homogenates with N-EtFOSA. This work provides evidence on the accumulation and transformation of N-EtFOSA in terrestrial invertebrates and will be helpful to explore the indirect sources of FOSA and PFOS in environmental biota. PMID- 29793106 TI - Microplastics in mussels sampled from coastal waters and supermarkets in the United Kingdom. AB - Global contamination of the marine environment by plastic has led to the discovery of microplastics in a range of marine species, including those for human consumption. In this study, the presence of microplastics and other anthropogenic debris in seawater and mussels (Mytilus edulis) from coastal waters of the U.K., as well as supermarket sources, was investigated. These were detected in all samples from all sites with spatial differences observed. Seawater samples taken from 6 locations (in triplicates) displayed 3.5 +/- 2.0 debris items/L on average (range: 1.5-6.7 items/L). In wild mussels sampled from 8 locations around the U.K. coastal environment, the number of total debris items varied from 0.7 to 2.9 items/g of tissue and from 1.1 to 6.4 items/individual. For the supermarket bought mussels, the abundance of microplastics was significantly higher in pre-cooked mussels (1.4 items/g) compared with mussels supplied live (0.9 items/g). Micro-FT-IR spectroscopy was conducted on 136 randomly selected samples, with 94 items characterized. The spectra found that 50% of these debris items characterized were microplastic, with an additional 37% made up of rayon and cotton fibers. The microplastic levels detected in the supermarket bought mussels present a route for human exposure and suggests that their quantification be included as food safety management measures as well as for environmental monitoring health measures. PMID- 29793107 TI - Biofiltration of methane using hybrid mixtures of biochar, lava rock and compost. AB - Using hybrid packing materials in biofiltration systems takes advantage of both the inorganic and organic properties offered by the medium including structural stability and a source of available nutrients, respectively. In this study, hybrid mixtures of compost with either lava rock or biochar in four different mixture ratios were compared against 100% compost in a methane biofilter with active aeration at two ports along the height of the biofilter. Biochar outperformed lava rock as a packing material by providing the added benefit of participating in sorption reactions with CH4. This study provides evidence that a 7:1 volumetric mixture of biochar and compost can successfully remove up to 877 g CH4/m3.d with empty-bed residence times of 82.8 min. Low-affinity methanotrophs were responsible for the CH4 removal in these systems (KM(app) ranging from 5.7 to 42.7 uM CH4). Sequencing of 16S rRNA gene amplicons indicated that Gammaproteobacteria methanotrophs, especially members of the genus Methylobacter, were responsible for most of the CH4 removal. However, as the compost medium was replaced with more inert medium, there was a decline in CH4 removal efficiency coinciding with an increased dominance of Alphaproteobacteria methanotrophs like Methylocystis and Methylocella. As a biologically-active material, compost served as the sole source of nutrients and inoculum for the biofilters which greatly simplified the operation of the system. Higher elimination capacities may be possible with higher compost content such as a 1:1 ratio of either biochar or lava rock, while maintaining the empty-bed residence time at 82.8 min. PMID- 29793108 TI - Manganese contamination affects the motor performance of wild northern quolls (Dasyurus hallucatus). AB - Neuromotor deficits are an important sign of manganese (Mn) toxicity in humans and laboratory animals. However, the impacts of Mn exposure on the motor function of wild animals remains largely unknown. Here, we assessed the impact of chronic exposure to Mn from active mining operations on Groote Eylandt, Australia on the motor function of the semi-arboreal northern quoll (Dasyurus hallucatus), an endangered species. The three motor tests conducted-maximum sprint speed on a straight run, manoeuvrability around a corner, and motor control on a balance beam-showed that elevated Mn body burden did not diminish performance of these traits. However, quolls with higher Mn body burden approached a corner at a significantly narrower range of speeds, due to a significantly lower maximum approach speed. Slower speeds approaching a turn may reduce success at catching prey and avoiding predators. Given that maximum sprint speed on a straight run was not affected by Mn body burden, but maximum speed entering a corner was, slower speeds approaching a turn may reflect compensation for otherwise impaired performance in the turn. PMID- 29793110 TI - Remembrance of inferences past: Amortization in human hypothesis generation. AB - Bayesian models of cognition assume that people compute probability distributions over hypotheses. However, the required computations are frequently intractable or prohibitively expensive. Since people often encounter many closely related distributions, selective reuse of computations (amortized inference) is a computationally efficient use of the brain's limited resources. We present three experiments that provide evidence for amortization in human probabilistic reasoning. When sequentially answering two related queries about natural scenes, participants' responses to the second query systematically depend on the structure of the first query. This influence is sensitive to the content of the queries, only appearing when the queries are related. Using a cognitive load manipulation, we find evidence that people amortize summary statistics of previous inferences, rather than storing the entire distribution. These findings support the view that the brain trades off accuracy and computational cost, to make efficient use of its limited cognitive resources to approximate probabilistic inference. PMID- 29793111 TI - Desire understanding in 2-year-old children: An eye-tracking study. AB - 'Much research has investigated children's understanding of others' mental states in terms of beliefs, but far less is known about their understanding of others' desires. To fill this gap, we used an eye-tracking paradigm to test 2-year-old children's desire understanding by measuring their anticipatory looking behavior as well as changes in their internal arousal (i.e., changes in pupil dilation). Children showed increased pupil dilation when an adult reached for an object she had previously emoted negatively towards (the object incongruent with her desire). Children also showed weaker evidence of anticipating that an adult will reach for an object that she had emoted positively towards (the object congruent with her desire). These results suggest that 2-year-olds robustly recognize whether or not an individual's actions are consistent with her desires, and seem to have a budding capacity to predict an individual's actions based on her desires. Thus, by age 2 years, children are on their way to acquiring a robust desire psychology. PMID- 29793109 TI - 17beta-estradiol as precursors of Cl/Br-DBPs in the disinfection process of different water samples. AB - During chlorine disinfection process, reactions between the disinfectant and 17beta-estradiol (E2) lead to the formation of halogenated disinfection byproducts (DBPs) which can be a risk to both ecosystem and human health. The degradation and transformation products of E2 in sodium hypochlorite (NaClO) disinfection processes of different water samples were investigated. The reaction kinetics research showed that the degradation rates of E2 were considerably dependent on the initial pH value and the types of water samples. In fresh water, synthetic marine aquaculture water and seawater, the reaction rate constant was 0.133 min-1, 2.067 min-1 and 2.592 min-1, respectively. The reasons for the above phenomena may be due to the different concentrations of bromide ions (Br-) in these three water samples which could promote the reaction between NaClO and E2. Furthermore, Br- could also cause the formation of brominated DBPs (Br-DBPs). The main DBPs, reaction centers and conceivable reaction pathways were explored. Seven halogenated DBPs have been observed including three chlorinated DBPs (Cl DBPs) and four Br-DBPs. The active sites of E2 were found to be the pentabasic cyclic ring and the ortho position of the phenol moiety as well as C9-C10 position. The identified Cl/Br-DBPs were also confirmed in actual marine aquaculture water from a shrimp pond. The comparison of bio-concentration factors (BCF) values based on calculation of EPI-suite showed that the toxicities of the Br-DBPs were stronger than that of their chloride analogues. The absorbable organic halogens (AOX) analysis also suggested that the DBPs produced in the marine aquaculture water were more toxic than that in the fresh water system. PMID- 29793112 TI - 3D-Printed membrane as an alternative to amniotic membrane for ocular surface/conjunctival defect reconstruction: An in vitro & in vivo study. AB - BACKGROUND: The aim of this study was to evaluate the surgical handling and clinical applicability of a specific 3D-printed membrane design fabricated using a gelatin, elastin and sodium hyaluronate blend for conjunctival reconstruction and compare it with amniotic membrane (AM), which is normally used in such surgeries. METHODS: 3D printing technique was employed to fabricate the membrane based on gradient design. Prior to printing, rheometry was employed to optimize the ink composition. The printed membranes were then fully characterized in terms of physical and mechanical properties. In vitro viability, proliferation and adhesion of human limbal epithelial cells were assessed using MTT assay and scanning electron microscopy (SEM), respectively. Prior to in vivo experiment, surgical handling of each membrane was evaluated by three surgeons. In vivo evaluation was conducted through implanting the gelatin-based membranes and AM on induced conjunctival defects in rabbits (n = 8). Clinical observations, including epithelialization, inflammation severity, scar tissue formation and presence of granulation tissue, were recorded from day 1 through day 28. Histological examination was performed on all enucleated eyes on day 28. In addition to H&E staining, specific stains including Periodic Acid Schiff staining, Masson's Trichrome staining and immuno-histochemical staining for alpha-SMA were further used to assess goblet cell proliferation, healed sub-epithelial stroma and scar tissue formation and the presence of myofibroblasts, respectively. RESULTS: Among all the examined compositions, a blend of 8% w/v gelatin, 2% w/v elastin and 0.5% w/v sodium hyaluronate was found to be appropriate for printing. The printed membranes had favorable optical characteristics (colorless and transparent), and the surgical handling was significantly easier compared to AM. Epithelial cells cultivated on the membranes indicated suitable viability and proliferation, and SEM images presented appropriate cell adhesion on the surface of the membranes. Clinical observations suggested similar epithelialization time (approximately 3 weeks) for both the membrane and AM grafted eyes but significantly lower levels of clinical inflammation in the membrane group from day 1 through day 28 (p = 0.01), which is a key advantage of using the printed membranes over the AM. Histological examination showed similar qualities in the healed epithelium in terms of cell morphology and cell layers. However, twice the density of goblet cells per 100 cells was observed in the gelatin-based membrane grafted group. Remnant of the degraded implant was seen in only 3 of the membranes, but in 7 of the AM grafted eyes. Inflammation and granulomatous reaction was significantly higher in sections containing the AM compared to membrane (p < 0.01 and p = 0.01, respectively). alpha-SMA staining was more evident, but not significantly different from the gelatin-based membrane, for the AM group (p = 0.25). CONCLUSION: The designed gelatin-based membrane offers the necessary physical and mechanical characteristics needed for successful ocular surface/conjunctival defect construction and may be considered a promising alternative to AM due to a more predictable degradation pattern, higher goblet cell density on the healed epithelium, less inflammation and reduced scar tissue formation. PMID- 29793113 TI - Assessment of the risk of antiangiogenic agents before and after surgery. AB - Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types, and thus, antiangiogenic agents have been studied for many years as potential therapeutic agents. Many different antiangiogenic agents, including monoclonal antibodies and multi-targeted tyrosine kinase inhibitors (TKIs), have been approved for various oncology indications, and promising clinical activity has been demonstrated. However, some of these agents have also been associated with serious safety concerns. Because angiogenesis is an important step in the wound healing process, agents targeting the angiogenesis pathway may interfere with wound healing, thus increasing the risk of surgical wound complications, such as dehiscence, surgical site bleeding, and wound infection. Nevertheless, antiangiogenic agents can be safely used in the perioperative setting if oncologists and surgeons are educated on the biology and pharmacokinetics of these agents. This review discusses the available published literature regarding surgical complications associated with the use of antiangiogenic agents and provides updated clinical recommendations on the optimal timing between surgery and antiangiogenic therapy. Due to the paucity of data surrounding this topic, current and future clinical trials need to evaluate prospectively the potential risks for surgical complications associated with antiangiogenic therapies to establish specific guidelines for their safe and effective use within the surgical oncology community. PMID- 29793114 TI - Soil types influence the fate of antibiotic-resistant bacteria and antibiotic resistance genes following the land application of sludge composts. AB - Sewage sludge was generally considered a significant reservoir of antibiotic resistance genes (ARGs) and could enter agricultural systems as fertilizer after composting. Soil types and the discrepancy of sludge composts could have influenced the fate of antibiotic-resistant bacteria (ARB) following the land application of sludge composts, which deserved to be clarified. Thus, the fate of ARB and ARGs following the land application of three types of sludge composts (A, B, and C) to three different soils (red soil, loess, and black soil) was investigated. The results showed that tetX, which was enriched the most during composting, did not affect the soil resistome, whereas tetG did. Soil types influenced the dynamics of ARB and ARGs significantly, whereas no significant difference was observed among compost types. The advantage of reducing ARGs during the composting process in compost B did not extend to land application. Land application of composts influenced the microbial community significantly at the early stage, but the microbial community returned to the control pattern gradually. Changes in the microbial community contributed more to the dynamics of ARGs in red and black soil compared with other factors, including co-selection from heavy metals, horizontal gene transfer, biomass and environmental factors, whereas horizontal gene transfer, reflected by intI1 levels, contributed the most in loess. PMID- 29793115 TI - Estimating chemical ecotoxicity in EU ecolabel and in EU product environmental footprint. AB - The EU Commission Ecolabel and the Product and Environmental Footprint (PEF) aim at promoting the development and consumption of greener products. The product aquatic toxicity score from these 2 methods may lead in some circumstances to opposite conclusions. Although this could be interpreted as an inconsistency, the score should not be compared to each other but used in a complementary way. In short, CDV provided a "full" product formula aquatic toxicity score, even if some chemicals may never reach or persist in freshwater ecosystems. The USEtox(r) score, by integrating fate and exposure, focuses on the potential toxicity of persistent-water-soluble chemicals at steady state. Since no risk or safety assessment can be conducted with USEtox(r) nor with the CDV, both are a hazard based scoring system. This short communication clarifies the difference between approaches underpinning the toxicity scores used in Ecolabel and PEF, providing guidance on how to interpret the results. PMID- 29793117 TI - Metagenomic insights into the microbiota profiles and bioaugmentation mechanism of organics removal in coal gasification wastewater in an anaerobic/anoxic/oxic system by methanol. AB - Coal gasification wastewater is a typical high phenol-containing, toxic and refractory industrial wastewater. Here, lab-scale anaerobic-anoxic-oxic system was employed to treat real coal gasification wastewater, and methanol was added to oxic tank as the co-substrate to enhance the removal of refractory organic pollutants. The results showed that the average COD removal in oxic effluent increased from 24.9% to 36.0% by adding methanol, the total phenols concentration decreased from 54.4 to 44.9 mg/L. GC-MS analysis revealed that contents of phenolic components and polycyclic aromatic hydrocarbons (PAHs) were decreased compared to the control and their degradation intermediates were observed. Microbial community revealed that methanol increased the abundance of phenolics and PAHs degraders such as Comamonas, Burkholderia and Sphingopyxis. Moreover, functional analysis revealed the relative abundance of functional genes associated with toluene, benzoate and PAHs degradation pathways was higher than that of control based on KEGG database. PMID- 29793116 TI - Patterns of Invasive Growth in Malignant Gliomas-The Hippocampus Emerges as an Invasion-Spared Brain Region. AB - BACKGROUND: Widespread infiltration of tumor cells into surrounding brain parenchyma is a hallmark of malignant gliomas, but little data exist on the overall invasion pattern of tumor cells throughout the brain. METHODS: We have studied the invasive phenotype of malignant gliomas in two invasive mouse models and patients. Tumor invasion patterns were characterized in a patient-derived xenograft mouse model using brain-wide histological analysis and magnetic resonance (MR) imaging. Findings were histologically validated in a cdkn2a-/- PDGF-beta lentivirus-induced mouse glioblastoma model. Clinical verification of the results was obtained by analysis of MR images of malignant gliomas. RESULTS: Histological analysis using human-specific cellular markers revealed invasive tumors with a non-radial invasion pattern. Tumors cells accumulated in structures located far from the transplant site, such as the optic white matter and pons, whereas certain adjacent regions were spared. As such, the hippocampus was remarkably free of infiltrating tumor cells despite the extensive invasion of surrounding regions. Similarly, MR images of xenografted mouse brains displayed tumors with bihemispheric pathology, while the hippocampi appeared relatively normal. In patients, most malignant temporal lobe gliomas were located lateral to the collateral sulcus. Despite widespread pathological fluid-attenuated inversion recovery signal in the temporal lobe, 74% of the "lateral tumors" did not show signs of involvement of the amygdalo-hippocampal complex. CONCLUSIONS: Our data provide clear evidence for a compartmental pattern of invasive growth in malignant gliomas. The observed invasion patterns suggest the presence of preferred migratory paths, as well as intra-parenchymal boundaries that may be difficult for glioma cells to traverse supporting the notion of compartmental growth. In both mice and human patients, the hippocampus appears to be a brain region that is less prone to tumor invasion. PMID- 29793118 TI - Efficient resource recycling from liquid digestate by microalgae-yeast mixed culture and the assessment of key gene transcription related to nitrogen assimilation in microalgae. AB - To determine the feasibility of microalgae-yeast mixed culture using the liquid digestate of dairy wastewater (LDDW) for biofuels and single cell protein (SCP) production, the cell growth, nutrient removal and outputs evaluation of the mono and mixed culture of Chlorella vulgaris and Yarrowia lipolytica in LDDW were investigated by adding glycerol as carbon source. The results showed that the mixed culture could enhance the biological utilization efficiency of nitrogen and phosphorus, and obtain higher yield of biomass (1.62 g/L), lipid (0.31 g/L), protein (0.51 g/L), and higher heating value (34.06 KJ/L). Compared with the mono culture of C. vulgaris, a decline of the transcription level in nitrate reductase and glutamine synthetase II genes in C. vulgaris was observed in the mixed culture when ammonia was sufficient. The results suggest the possibility of using the mixed culture for the efficient treatment of LDDW and resources recycling. PMID- 29793119 TI - Bioaugmentation potential of a newly isolated strain Sphingomonas sp. NJUST37 for the treatment of wastewater containing highly toxic and recalcitrant tricyclazole. AB - In order to develop an effective bioaugmentation strategy for the removal of highly toxic and recalcitrant tricyclazole from wastewater, a tricyclazole degrading strain was firstly successfully isolated and identified as Sphingomonas sp. NJUST37. In batch reactors, 100 mg L-1 tricyclazole could be completely removed within 102 h, which was accompanied by significant biomass increase, TOC and COD removal, as well as toxicity reduction. Chromatography analysis and density functional theory simulation indicated that monooxygenation occurred firstly, followed by triazole ring cleavage, decyanation reaction, hydration reaction, deamination, dihydroxylation and final mineralization reaction. Tricyclazole biodegradation condition by NJUST37 was optimized in terms of temperature, pH, tricyclazole concentration and additional carbon and nitrogen sources. After the inoculation of NJUST37 into a pilot-scale powdered activated carbon treatment tank treating real fungicide wastewater, tricyclazole removal efficiency increased to higher than 90%, demonstrating the great potential of NJUST37 for bioaugmentation particularly on tricyclazole biodegradation in practice. PMID- 29793120 TI - Socioeconomic status of parents with children participating on youth club sport teams. AB - OBJECTIVES: To describe the socioeconomic status, measured by household income and educational attainment, of parents with children participating on youth club sport teams. DESIGN: Cross-sectional survey. SETTING: Local sport events. PARTICIPANTS: 949 parents (571 female) of youth athletes between 10 and 18 years old were recruited at club team events and practices to complete an anonymous questionnaire. MAIN OUTCOME MEASURES: SES variables included total household income (THI) and educational attainment. Sport specialization was classified as low, moderate, or high using a previously utilized 3-point specialization scale. Chi-square tests were used to compare frequencies SES categories with child specialization. RESULTS: Parents reported spending a median of 1500 [500-3000] USD per year on their children's club sports activities. Most parents reported a THI greater than 100,000 USD per year and a bachelor's degree or higher level of education. Parents in the higher THI categories were more likely to have a child that is highly specialized in one sport. CONCLUSION: The current youth sports system in the United States, which emphasizes year-round participation on club teams, may be limiting the participation of families without the resources to participate in this system. PMID- 29793121 TI - Head coaches' attitudes towards injury prevention and use of related methods in professional basketball: A survey. AB - OBJECTIVES: To investigate the practices and attitudes of professional basketball head coaches towards injury prevention. DESIGN: Survey. SETTING: Elite-level basketball. PARTICIPANTS: Head coaches of all 366 German professional teams. MAIN OUTCOME MEASURES: Use of injury risk screening methods, rated importance of different musculoskeletal injuries and rated effectiveness of preventive interventions. RESULTS: Eighty-three of 366 invited coaches (23%) responded to the survey. No non-response bias was detected. Only one of three teams conducts systematic injury screenings. The most commonly used test was the functional movement screen (73.1% of users), while balance and strength testing (both 38.5%) were least prevalent. Top-rated preventive interventions included balance and strength training, training of functional movement patterns, and stretching. In contrast, passive interventions, e.g. the use of orthoses, were not considered effective. The involvement of a health professional (e.g. physiotherapist) was associated with the performance of injury screening, but not with the choice of specific tests or preventive strategies. CONCLUSIONS: The methods applied to conduct injury screening and prevent musculoskeletal disorders in German professional basketball teams seem only partially backed by scientific evidence. Although not correlated with the tests and interventions used, the involvement of health-related stakeholders might help to identify players at increased injury risk. PMID- 29793122 TI - Intra- and interrater reliability of the 'lumbar-locked thoracic rotation test' in competitive swimmers ages 10 through 18 years. AB - OBJECTIVES: Measuring thoracic spine mobility can be of interest to competitive swimmers as it has been associated with shoulder girdle function and scapular position in subjects with and without shoulder pain. At present, no reliability data of thoracic spine mobility measurements are available in the swimming population. This study aims to evaluate the within-session intra- and interrater reliability of the "lumbar-locked rotation test" for thoracic spine rotation in competitive swimmers aged 10 to 18 years. This reliability study is part of a larger prospective cohort study investigating potential risk factors for the development of shoulder pain in competitive swimmers. DESIGN: Within-session, intra- and inter-rater reliability. SETTING: Competitive swimming clubs in Belgium. PARTICIPANTS: 21 competitive swimmers. MAIN OUTCOME MEASURES: Intra- and inter-rater reliability of the lumbar-locked thoracic rotation test. RESULTS: Intraclass correlation coefficients (ICCs) ranged from 0.91 (95% CI 0.78 to 0.96) to 0.96 (0.89-0.98) for intra-rater reliability. Results for inter-rater reliability ranged from 0.89 (0.72-0.95) to 0.86 (0.65-0.94) respectively for right and left thoracic rotation. CONCLUSION: Results suggest good to excellent reliability of the lumbar-locked thoracic rotation test, indicating this test can be used reliably in clinical practice. PMID- 29793123 TI - The Beighton score as a predictor of Brighton criteria in sport and dance. AB - OBJECTIVES: To determine the efficacy of using the Beighton joint hypermobility score as a predictor of Brighton criteria components, considering the influence of gender and sports participation. DESIGN: Cross sectional study design. SETTING: A University. PARTICIPANTS: Sixty-five female rugby players, 38 male rugby players, 61 netball players, 42 female dancers, 40 male controls and 40 female controls. MAIN OUTCOME MEASURES: The Beighton score was assessed using the Beighton and Horan Joint Mobility Index. The Brighton criteria was used to assess joint hypermobility syndrome. A binary logistic regression was performed for a pooled sample (n = 286), and subsequently for gender and sport to assess the Beighton score as a predictor of Brighton criteria. RESULTS: Beighton scores were found to be a predictor of arthralgia (P = 0.002), dislocation and subluxation (P = 0.048) in the pooled analysis; a predictor of dislocation and subluxation (P = 0.047) in males and arthralgia (P = 0.001) in females. Beighton scores were a predictor of arthralgia in female rugby (P = 0.003) and in female controls (P = 0.012). CONCLUSIONS: The potential of the Beighton score to predict joint arthralgia and dislocation/subluxation may allow clinicians to implement effective injury prevention strategies. PMID- 29793124 TI - How to manage patellofemoral pain - Understanding the multifactorial nature and treatment options. AB - Patellofemoral pain (PFP) is one of the most prevalent conditions within sports medicine, orthopaedic and general practice settings. Long-term treatment outcomes are poor, with estimates that more than 50% of people with the condition will report symptoms beyond 5 years following diagnosis. Additionally, emerging evidence indicates that PFP may be on a continuum with patellofemoral osteoarthritis. Consensus of world leading clinicians and academics highlights the potential benefit of delivering tailored interventions, specific to an individual's needs, to improve patient outcome. This clinical masterclass aims to develop the reader's understanding of PFP aetiology, inform clinical assessment and increase knowledge regarding individually tailored treatment approaches. It offers practical application guidance, and additional resources, that can positively impact clinical practice. PMID- 29793125 TI - Assessment of cam morphology of the hip with ultra sound imaging by physical therapists is reliable and valid. AB - BACKGROUND: Femoroacetabular impingement syndrome is considered present when a combination of clinical symptoms, signs and morphological features of the hip co exist. Imaging is increasingly popular in primary health care settings with physical therapists performing ultrasound (US). OBJECTIVE: The aim of this study was to assess the diagnostic accuracy and inter-rater reliability of ultrasound in determining presence of cam morphology. DESIGN: A concurrent validity and inter-rater reliability study. METHODS: The presence of cam morphology of the hip was determined by alpha angle measures using Kinovea software. A cam was defined present when the alpha angle >60 degrees . The index test was US and radiographs served as a gold standard. RESULTS: Correlation between the radiographic alpha angle and ultrasound measures was r = 0.82 (p < 0.01). Inter-rater reliability was high with an ICC of 0.74 (95% CI 0.61-0.84). The predictive value for presence of cam morphology had a sensitivity of 79% and a specificity of 94%. The positive predictive value was 79% whereas the negative predictive value was 94%. Total accuracy was 90%. CONCLUSIONS: Ultrasound conducted by trained physical therapists is a valid, reliable, specific and sensitive diagnostic tool to assess the presence of cam morphology. PMID- 29793126 TI - Effect of manual therapy versus proprioceptive neuromuscular facilitation in dynamic balance, mobility and flexibility in field hockey players. A randomized controlled trial. AB - OBJECTIVES: To compare the effectiveness of a specific Manual Therapy (MT) protocol applied to field hockey players (FHP), versus a Proprioceptive Neuromuscular Facilitation (PNF) protocol, in the improvement of dynamic balance, active range of movement and lumbar flexibility one-week and four-weeks after the treatment. DESIGN: Randomized controlled trial. Participants were assigned to 2 groups: MT and PNF. 30 min' sessions were performed once a week for three weeks. Three evaluations were performed: basal, one-week and four-weeks post-treatment. SETTING: University of Valencia (Spain). PARTICIPANTS: 22 in MT group and 20 in PNF group. MAIN OUTCOME MEASURES: Dynamic Balance, measured with Star Excursion Balance Test; Active Range of Motion (ROM), using a manual goniometer and Lumbar Flexibility, assessed with Fingertip-to-floor test. RESULTS: Both groups significantly improved in lateral and medial dynamic balance one-week post treatment (p < 0.05); but the improvement in the MT group lasted until the fourth week after treatment in both reaches (lateral and medial) (p < 0.05). MT group also obtained significant improvements in dorsal flexion of the ankle in the fourth-week post-treatment (p < 0.05) and in lumbar flexibility one-week post treatment (p < 0.05). CONCLUSIONS: MT and PNF improve dynamic balance one-week post-treatment; however, the improvement obtained through MT is maintained four weeks later. Only MT improves dorsal flexion of the ankle four-weeks post treatment and lumbar flexibility one-week post-treatment. PMID- 29793127 TI - Effects of sodium salicylate on the determination of Lead-210/Bismuth-210 by Cerenkov counting. AB - Due to the nature of Cerenkov radiation and instrumental limitations, detection efficiencies of 210Bi by Cerenkov counting are generally quite low (~15%). Sodium salicylate, acting as a wavelength shifter, has been used to improve the detection efficiency of Cerenkov photons. In this study, we found that the addition of sodium salicylate could significantly increase the counting efficiencies of 210Pb/210Bi in aqueous samples. Meanwhile, a sharp increase of the counting efficiency for the alphas from 210Po was also observed with the addition of high concentration of sodium salicylate, implying that scintillation light rather than Cerenkov photons from the alphas has been produced. Detailed studies about the effects of sodium salicylate on the counting of 210Pb, 210Bi and 210Po were conducted. At low concentration (< 0.5 mg g-1) of sodium salicylate, only a small increase in Cerenkov counting efficiency for 210Bi by the wavelength-shifting effect could be observed. Meanwhile, the counting efficiency for 210Bi at high concentration (> 1 mg g-1) of sodium salicylate would significantly increase due to the scintillation effect. PMID- 29793129 TI - Global Mittag-Leffler stability and synchronization analysis of fractional-order quaternion-valued neural networks with linear threshold neurons. AB - This paper talks about the stability and synchronization problems of fractional order quaternion-valued neural networks (FQVNNs) with linear threshold neurons. On account of the non-commutativity of quaternion multiplication resulting from Hamilton rules, the FQVNN models are separated into four real-valued neural network (RVNN) models. Consequently, the dynamic analysis of FQVNNs can be realized by investigating the real-valued ones. Based on the method of M-matrix, the existence and uniqueness of the equilibrium point of the FQVNNs are obtained without detailed proof. Afterwards, several sufficient criteria ensuring the global Mittag-Leffler stability for the unique equilibrium point of the FQVNNs are derived by applying the Lyapunov direct method, the theory of fractional differential equation, the theory of matrix eigenvalue, and some inequality techniques. In the meanwhile, global Mittag-Leffler synchronization for the drive response models of the addressed FQVNNs are investigated explicitly. Finally, simulation examples are designed to verify the feasibility and availability of the theoretical results. PMID- 29793128 TI - Convolutional neural networks for seizure prediction using intracranial and scalp electroencephalogram. AB - Seizure prediction has attracted growing attention as one of the most challenging predictive data analysis efforts to improve the life of patients with drug resistant epilepsy and tonic seizures. Many outstanding studies have reported great results in providing sensible indirect (warning systems) or direct (interactive neural stimulation) control over refractory seizures, some of which achieved high performance. However, to achieve high sensitivity and a low false prediction rate, many of these studies relied on handcraft feature extraction and/or tailored feature extraction, which is performed for each patient independently. This approach, however, is not generalizable, and requires significant modifications for each new patient within a new dataset. In this article, we apply convolutional neural networks to different intracranial and scalp electroencephalogram (EEG) datasets and propose a generalized retrospective and patient-specific seizure prediction method. We use the short-time Fourier transform on 30-s EEG windows to extract information in both the frequency domain and the time domain. The algorithm automatically generates optimized features for each patient to best classify preictal and interictal segments. The method can be applied to any other patient from any dataset without the need for manual feature extraction. The proposed approach achieves sensitivity of 81.4%, 81.2%, and 75% and a false prediction rate of 0.06/h, 0.16/h, and 0.21/h on the Freiburg Hospital intracranial EEG dataset, the Boston Children's Hospital-MIT scalp EEG dataset, and the American Epilepsy Society Seizure Prediction Challenge dataset, respectively. Our prediction method is also statistically better than an unspecific random predictor for most of the patients in all three datasets. PMID- 29793130 TI - Anxiety, memories and coping in patients undergoing intracranial tumor surgery. AB - OBJECTIVES: The diagnosis and the surgical removal of a brain tumor can have serious impact on the quality of life of a patient. The question rises, whether having more or just less memories of the procedure is better for coping with such an event. Furthermore, for preoperative information of future patients it is important to know how patients process their emotions and memories. The primary objective of this study was to investigate the link between preoperative anxiety, the perioperative experience and the quantity and quality of postoperative memories in patients who underwent intracranial tumor surgery. PATIENTS AND METHODS: This study was a retrospective observational study; all patients who underwent intracranial tumor surgery at the Erasmus Medical Centre Rotterdam between January 1st 2014 and December 31st 2015 were identified. In May 2016, all patients who were not registered as deceased were sent a questionnaire about their anxieties, perceptions and memories of the perioperative period. RESULTS: In total 476 patients were included. 272 patients responded, which resulted in a response rate of 57.14%. In the general anesthesia (GA) group there was a significant negative correlation between anxiety in the perioperative period and the quantity and quality of memories. In the awake craniotomy group, there was a significant negative correlation between anxiety after the operation and the quantity of memories. CONCLUSION: Patients in the GA group who experienced anxiety in the perioperative period had less quantity and quality of memories and less patient satisfaction. Patients in the AC group who experienced anxiety after the operation had only a lower quantity of the memory; there was no correlation with patient satisfaction. PMID- 29793131 TI - TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression. AB - Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4+CD25+ Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl4/CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH. PMID- 29793132 TI - pH responsive label-assisted click chemistry triggered sensitivity amplification for ultrasensitive electrochemical detection of carbohydrate antigen 24-2. AB - Sensitivity amplification strategy by implementing click chemistry in the construction of biosensing interface can efficiently improve the performance of immunosensor. Herein, we developed a sandwich-type amperometric immunosensor for ultrasensitive detection of carbohydrate antigen 24-2 (CA 242) based on pH responsive label-assisted click chemistry triggered sensitivity amplification strategy. The sensitivity of amperometric immunosensor relies on the current response differences (DeltaI) caused by per unit concentration target analyte. The pH responsive Cu2+-loaded polydopamine (CuPDA) particles conjugated with detection antibodies were employed as labels, which can release Cu(II) ions by regulating pH. In the presence of ascorbic acid (reductant), Cu(II) ions were reduced to Cu(I) ions. Azide-functionalized double-stranded DNA (dsDNA) as signal enhancer was immobilized on the substrate through Cu+-catalyzed azide/alkyne cycloaddition reaction. With the help of the click reaction, the DeltaI caused by target was elevated prominently, resulting in sensitivity amplification of the immunosensor. Under optimal condition, the proposed immunosensor exhibited excellent performance with linear range from 0.0001 to 100 U mL-1 and ultralow detection limit of 20.74 MUU mL-1. This work successfully combines click chemistry with pH-responsive labels in sandwich-type amperometric immunosensor, providing a promising sensitivity amplification strategy to construct immunosensing platform for analysis of other tumor marker. PMID- 29793133 TI - An ultrasensitive and selective electrochemical aptasensor based on rGO MWCNTs/Chitosan/carbon quantum dot for the detection of lysozyme. AB - An aptamer-based method is described for the electrochemical determination of lysozyme. A glassy carbon electrode was modified with a nanocomposite composed of reduced graphene oxide (rGO), multi-walled carbon nanotubes (MWCNTs), chitosan (CS), and a synthesized carbon quantum dot (CQD) from CS. The composition of the nanocomposite (rGO-MWCNT/CS/CQD) warrants a high surface-to-volume ratio, high conductivity, high stability, and great electrocatalytic activity. This nanocomposite provides a suitable site for better immobilization of aptamers due to the existence of many amino and carboxyl functional groups, and remaining oxygen-related defects properties in rGO. In addition, this nanocomposite allows considerable enhancement of the electrochemical signal and contributes to improving sensitivity. The amino-linked lysozyme aptamers were immobilized on the nanocomposite through covalent coupling between the amino groups of the aptamer and the amino groups of the nanocomposite using glutaraldehyde (GLA) linker. The modified electrode was characterized by electrochemical methods including differential pulse voltammetry (DPV), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). In the presence of lysozyme, the immobilized aptamer selectively caught the target lysozyme on the electrode interface that leads to a decrease in the DPV peak current and an increase in Charge Transfer Resistance (Rct) in EIS as an analytical signal. Using the obtained data from DPV and EIS techniques, two calibration curves were drawn. The anti-lysozyme aptasensor proposed has two very low LODs. These measures are 3.7 and 1.9 fmol L-1 within the wide detection ranges of 20 fmol L-1 to 10 nmol L-1, and 10 fmol L-1 to 100 nmol L-1 for DPV and EIS calibration curves, respectively. The GCE/rGO-MWCNT/CS/CQD showed sensitivity, high reproducibility, specificity and rapid response for lysozyme which can be used in biomedical fields. PMID- 29793134 TI - Voxel-based automated detection of focal cortical dysplasia lesions using diffusion tensor imaging and T2-weighted MRI data. AB - The aim of this study was to automatically detect focal cortical dysplasia (FCD) lesions in patients with extratemporal lobe epilepsy by relying on diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) data. We implemented an automated classifier using voxel-based multimodal features to identify gray and white matter abnormalities of FCD in patient cohorts. In addition to the commonly used T2-weighted image intensity feature, DTI-based features were also utilized. A Gaussian processes for machine learning (GPML) classifier was tested on 12 patients with FCD (8 with histologically confirmed FCD) scanned at 1.5 T and cross-validated using a leave-one-out strategy. Moreover, we compared the multimodal GPML paradigm's performance with that of single modal GPML and classical support vector machine (SVM). Our results demonstrated that the GPML performance on DTI-based features (mean AUC = 0.63) matches with the GPML performance on T2-weighted image intensity feature (mean AUC = 0.64). More promisingly, GPML yielded significantly improved performance (mean AUC = 0.76) when applying DTI-based features to multimodal paradigm. Based on the results, it can also be clearly stated that the proposed GPML strategy performed better and is robust to unbalanced dataset contrary to SVM that performed poorly (AUC = 0.69). Therefore, the GPML paradigm using multimodal MRI data containing DTI modality has promising result towards detection of the FCD lesions and provides an effective direction for future researches. PMID- 29793135 TI - Accuracy of magnetic resonance venography in diagnosing cerebral venous sinus thrombosis. AB - OBJECTIVES: The non-specific clinical manifestations and lack of effective diagnostic techniques have made cerebral venous sinus thrombosis (CVST) difficult to recognize and easy to misdiagnose. Several studies have suggested that different types of magnetic resonance venography (MRV) have advantages in diagnosing CVST. We conducted this meta-analysis to assess the accuracy of MRV in identifying CVST. MATERIAL AND METHODS: We searched the Embase, PubMed, and Chinese Biomedical (CBM) databases comprehensively to retrieve eligible articles up to Mar 31, 2018. The methodological quality of each article was evaluated individually. The summary diagnostic accuracy of MRV for CVST was obtained from pooled analysis with random-effects models. Sensitivity analysis, subgroup analysis, and meta-regression were used to explore the sources of heterogeneity. A trim and fill analysis was conducted to correct the funnel plot asymmetry. RESULTS: The meta-analysis synthesized 12 articles containing 27 cohorts with a total of 1933 cases. The pooled sensitivity and specificity were 0.86 (95% CI: 0.83, 0.89) and 0.94 (95% CI: 0.93, 0.95), respectively. The pooled diagnostic odds ratio (DOR) was 75.24 (95% CI: 38.33, 147.72). The area under the curve (AUC) was 0.9472 (95% CI: 0.9229, 0.9715). Subgroup analysis and meta-regression analysis revealed the technical types of MRV and the methods of counting cases contributing to the heterogeneity. The trim and fill method confirmed that publication bias has little effect on our results. CONCLUSIONS: MRV has excellent diagnostic performance and is accurate in confirming CVST. PMID- 29793136 TI - Effects of gestational hypertension and pre-eclampsia in mRNA expression of fibrinolysis genes in primary cultured human umbilical vein endothelial cells. AB - Hypertension disorders (HD) and pre-eclampsia (PRE) are leading causes of maternal deaths worldwide. PRE is associated with vascular endothelial dysfunction and with deregulation of the fibrinolysis pathway genes. Fibrinolysis is the fibrin clot hydrolysis process catalyzed by plasmin, a proteolytic enzyme formed from plasminogen. Plasminogen is cleaved by tissue-type (tPA) and urokinase-type (uPA) activators and inhibited by the plasminogen activator inhibitors type-1 (PAI-1) and type-2 (PAI-2). The whole process maintains blood hemostasis. This study aims to assess PAI-1, PAI-2, tPA and uPA mRNA expression in primary cultured human umbilical vein endothelial cells (HUVEC) isolated and cultured from healthy, HD and PRE women. Results show that PAI-1 and PAI-2 mRNA decreased in HD-HUVEC, whereas PAI-1 and uPA decreased in PRE-HUVEC cultures compared to control ones. Notably, the expression ratio between pro- and anti fibrinolytic actors remained unchanged among the studied groups. It seems that newborn's hemostasis is maintained balanced probably by a compensatory mechanism that involves changes in the fibrinolysis gene expression profile. The real impact of these changes in mRNA expression is unknown, however, it is suggested that these changes could be associated with an increased predisposition to vascular disease development in the progeny. PMID- 29793138 TI - Computation of marginal distributions of peak-heights in electropherograms for analysing single source and mixture STR DNA samples. AB - Current models for single source and mixture samples, and probabilistic genotyping software based on them used for analysing STR electropherogram data, assume simple probability distributions, such as the gamma distribution, to model the allelic peak height variability given the initial amount of DNA prior to PCR amplification. Here we illustrate how amplicon number distributions, for a model of the process of sample DNA collection and PCR amplification, may be efficiently computed by evaluating probability generating functions using discrete Fourier transforms. PMID- 29793139 TI - The use of low-intensity pulsed ultrasound in treating delayed union of fifth metatarsal fractures. AB - BACKGROUND: There are no studies looking at the success rate of low-intensity pulsed ultrasound (LIPUS) in fifth metatarsal fracture delayed unions to our knowledge. The aim of this study is to investigate the use of LIPUS treatment for delayed union of fifth metatarsal fractures. METHODS: A retrospective review of patients who were treated with LIPUS following a delayed union of fifth metatarsal fracture was conducted over a three-year period. RESULTS: There were thirty patients (9 males, 21 females) in this cohort. The average age was 39.3 years. Type 2 fractures made up 43% of our cohort. Twenty-seven (90%) patients went on to progress to union clinically and radiologically following LIPUS treatment. Smoking (p=0.014) was predictive of non-union. Assuming that there were 10 delayed unions a year and 6 went on to non-union as previously suggested by a systematic review, the cost savings of using LIPUS (90% success rate; 10 LIPUS machine and surgery for 1 non-union) vs operative intervention (surgery for 6 non-union) equates to a cost saving of L7765 a year. CONCLUSION: There is a role for the use of LIPUS in delayed union of fifth metatarsal fractures and can serve as an adjunct prior to consideration of surgery. The findings of this study also suggest the use of LIPUS to be a cost effective treatment modality compared to surgical management. LEVEL OF EVIDENCE: Level 4. PMID- 29793140 TI - Effectiveness of a voluntary family befriending service: a mixed methods evaluation using the Donabedian model. AB - OBJECTIVES: Voluntary befriending schemes operate in many countries, promoting public health by supporting vulnerable individuals and families. Use of third sector and voluntary services to complement health and social care provision is increasingly important globally in the context of economic and demographic challenges, but the evidence base around such collaborations is limited. This article reports the results of operational evaluation research seeking to use robust routine work to generate transferable findings for use by those commissioning and providing services. The subject of our evaluation research is 'Home-Start Suffolk' (HSS) in Suffolk County, UK, an example of a third sector organisation commissioned to support the public health offer to local families. STUDY DESIGN: This evaluation research used the Donabedian framework, which assesses the structure, process and outcome in delivery of health services. METHODS: Methods included a cross-sectional stakeholder survey with qualitative and quantitative elements (n = 96), qualitative interviews (n = 41) and quantitative analysis of the service's routine data (5740 visits) for the period from 01 July 2014 to 01 July 2016. RESULTS: Triangulation of data from each component revealed that HSS was perceived by diverse stakeholders to successfully support families in need of additional help. HSS service users perceived the service to offer greater flexibility, to be tailored to their needs and to be more trustworthy and supportive than statutory services. Volunteering with HSS enabled people to feel productive in their community and gain new skills. Managers of social care services perceived that HSS activity decreased burden on their staff. These benefits were facilitated through a long-standing organisational HSS structure and relationships between HSS and social care. Challenges posed by service provision by a third sector organisation included the need for volunteers to negotiate the boundary between being a friend and a professional outside of a professional framework. Quantitative analysis of impact was limited by the poor quality of routinely collected administrative data, highlighting the importance of planning processes for data collection with evaluation in mind. CONCLUSION: We believe that the results of this evaluation research provide transferrable lessons. They demonstrate how a third sector organisation with a long-standing structure and relationships with statutory services was able to reduce perceived service burden while also offering support in a more flexible and tailored way greatly valued by service users. PMID- 29793137 TI - 3-O sulfation of heparin leads to hepatotropism and longer circulatory half-life. AB - INTRODUCTION: Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry. MATERIALS & METHODS: Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer). Half of the n12mer was modified with a 3-O sulfate on a single GlcNS sugar producing the 3-O sulfated heparin (12mer). Wildtype (WT), Stabilin-1 knock-out (KO), and Stabilin 2 KO C57BL/6 mice were developed and used for metabolic studies and provided as a source for primary liver sinusoidal endothelial cells. RESULTS & CONCLUSIONS: Human and mouse Stabilin-2 receptors had very similar endocytosis rates of both the 12mer and n12mer, suggesting that they are functionally similar in primary cells. Subcutaneous injections of the n12mer and 12mer revealed that the 12mer had a much longer half-life in circulation and a higher accumulation in liver. The n12mer never accumulated in circulation and was readily excreted by the kidneys before liver accumulation could occur. Liver sinusoidal endothelial cells from the Stabilin-2 KO mice had lower uptake rates for both dodecamers, whereas, the Stabilin-1 KO mice had lower endocytosis rates for the 12mer than the n12mer. 3-O sulfation of heparin is correlated to both a longer circulatory half-life and hepatotropism which is largely performed by the Stabilin receptors. PMID- 29793141 TI - New contributions to Gruberia lanceolata (Gruber, 1884) Kahl, 1932 based on analyses of multiple populations and genes (Ciliophora, Heterotrichea, Gruberiidae). AB - Gruberia Kahl, 1932 is a species-poor genus comprising only seven named species. Most of these species have not been reinvestigated since the original reports. In the present work, we investigated the taxonomy and phylogeny of Gruberia lanceolata (Gruber, 1884) Kahl, 1932 based on analyses of morphology and multiple gene sequences from four South Korean populations. This species is mainly characterized by a well-developed peristome region, segmented paroral membrane, and moniliform macronucleus. Some morphological features were not stable among the four populations investigated, such as body shape and size, cell color, and the ratio of oral length to body length. However, our molecular analyses of four different genetic markers - three nuclear DNA markers (18S rDNA, ITS1-5.8S-ITS2 region, D1D2 of 28S rDNA) and one mitochondrial (mt) marker (CO1 gene) - indicated that all Korean populations examined were the same species. Based on our present findings and historic works, we propose that G. calkinsi, G. aculeata, and G. beninensis are junior synonyms of G. lanceolata. PMID- 29793142 TI - Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid. AB - Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 +/- 0.01 uM) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 +/- 1.27 uM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 A which might be responsible for higher activity compared to Kojic acid. PMID- 29793143 TI - Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids. AB - A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones's oxidation were employed to obtain mono-, di- and tri oxolupanes, starting from calenduladiol (1) and lupeol (3). All the derivatives showed a selective inhibition of butyrylcholinesterase over acetylcholinesterase (BChE vs. AChE). A kinetic study proved that compounds 2 and 9, the more potent inhibitors of the series, act as competitive inhibitors. Molecular modeling was used to understand their interaction with BChE, the role of carbonyl at C-16 and the selectivity towards this enzyme over AChE. These results indicate that oxidation at C-16 of the lupane skeleton is a key transformation in order to improve the cholinesterase inhibition of these compounds. PMID- 29793144 TI - Structural confirmation and spectroscopic study of a biomolecule: Norepinephrine. AB - The present work deals with the conformational and vibrational spectroscopic study of an important bio-molecule named norepinephrine in gas phase. The FTIR and FTRaman spectrum of norepinephrine in amorphous form were recorded in wavenumber range 4000-400 cm-1 and 4000-50 cm-1 respectively. We have investigated twenty-seven stable conformational structures of norepinephrine molecule. All the calculations have been done using Density Functional Theory with exchange functional B3LYP incorporated with the 6-31++G(d, p) basis set. The effect of hydrochloride on different bond lengths, bond angles and dihedral angles in the most stable conformer has also been studied. The total potential energy distribution for both the most stable conformer and the most stable conformer in hydrochloride was performed with the help Normal coordinate analysis method. Most of the calculated vibrational frequencies are in good agreement with the experimental frequencies. The natural bond orbital analysis was also performed to ensure the stability of electronic structures of norepinephrine. To know chemical reactivity of norepinephrine molecule we have calculated the energy gap between HOMO and LUMO orbitals and it has found above 5 eV in all the conformers. PMID- 29793145 TI - Mechanistic approach to study conjugation of nanoparticles for biomedical applications. AB - Interaction of nanoparticles with biological systems turns out to be vibrant for their efficient application in biomedical field. Here, we have shown antibiotic amakicin loaded nanoparticles are responsible for the dual role as reducing and stabilizing the silver nanoparticles without the use of any undesired chemicals. Synthesized nanoparticles are well-dispersed having quasi spherical morphology with an average particle size around 10-11 nm. Crystallinity of nanoparticles was measured using selected area electron diffraction (SAED) and powder XRD analysis which show that particles are perfectly crystalline with cubic phase of geometry. UV-Vis, FTIR and circular dichroism (CD) analysis explained the presence and interaction of antibiotic on the nanoparticle's surface. Amakicin functionalized Ag nanoparticles used in this study have shown enhanced antibacterial activity against E. coli. These studies will help in designing an in-depth understanding that how nanostructures can possibly interact with biological systems. PMID- 29793146 TI - Development of a novel tridentate ligand for colorimetric detection of Mn2+ based on AgNPs. AB - A novel tridentate ligand nitrilotris(methylene)tris(1,2,3-triazole)triacetate (NTTTA) has been synthesized by click reaction and followed with ester hydrolysis reaction. The silver nanoparticles (AgNPs) were then modified and stabilized by this ligand, and subsequently been employed for the highly selective and sensitive colorimetric detection of Mn2+ in aqueous solution. The presence of Mn2+ can cause the aggregation of AgNPs, which leads to the color change of the dispersion from yellow to brown, as well as the decrease and red-shift of the surface plasmon resonance absorption. The detection limit of Mn2+ was as approximately 0.5 MUM by the naked eyes. UV-vis spectroscopy analysis showed a good linear relationship between the logarithm of the ratios (A550/A395) and the concentration of Mn2+over the range of 0.05 MUM-10 MUM, and the LOD was calculated to be 12.6 nM (S/N = 3). The present assay showed good simplicity without the need of adjusting the pH value. The feasibility of this technique was evaluated for successful detection of Mn2+ in tap water and lake water samples, with good recoveries. PMID- 29793147 TI - Study on the interactions between toxic nitroanilines and lysozyme by spectroscopic approaches and molecular modeling. AB - Being exogenous environmental pollutants, nitroanilines (NAs) are highly toxic and have mutagenic and carcinogenic activity. Being lack of studies on interactions between NAs and lysozyme at molecular level, the binding interactions of lysozyme with o-nitroaniline (oNA), m-nitroaniline (mNA) and p nitroaniline (pNA) were investigated by means of steady-state fluorescence, synchronous fluorescence, UV-vis absorption spectroscopy, as well as molecular modeling. The experimental results revealed that the fluorescence of lysozyme is quenched by oNA and mNA through a static quenching, while the fluorescence quenching triggered by pNA is a combined dynamic and static quenching. The number of binding sites (n) and the binding constant (Kb) corresponding thermodynamic parameters DeltaH?, DeltaS?, DeltaG? at different temperatures were calculated. The reactions between NAs and lysozyme were spontaneous and entropy driven and the binding of NAs to lysozyme induced conformation changes of lysozyme. The difference of the position of -NO2 group affected the binding and the binding constants Kb decreased in the following pattern: Kb (pNA) >Kb (mNA) >Kb (oNA). Molecular docking studies were performed to reveal the most favorable binding sites of NAs on lysozyme. Our recently results could offer mechanistic insights into the nature of the binding interactions between NAs and lysozyme and provide information about the toxicity risk of NAs to human health. PMID- 29793148 TI - Post-traumatic stress symptom development as a function of changing witnessing in home violence and changing peer relationship quality: Evaluating protective effects of peer relationship quality. AB - In the present study, witnessing in-home violence and peer relationship quality are evaluated as to their relative impact on Post Traumatic Stress (PTS) symptoms among children aged 8 to 17 investigated by child protective services (CPS) for maltreatment exposure. The sample included 2151 children from the National Survey of Child and Adolescent Well-Being II (NSCAW II). Linear growth models were estimated to assess associations between changes in PTS symptoms, witnessing in home violence, and peer relationship quality over time. Greater frequency of witnessing in-home violence at baseline (i.e. wave 1) was associated with higher baseline PTS symptoms (beta = 0.44). Increases in witnessing in-home violence frequency over time (average annual change across three years) had a strong association with increases in PTS symptoms over time (beta = 0.88). Baseline peer relationship quality was associated with fewer PTS symptoms at baseline (beta = 0.45). Increases in peer relationship quality over time were strongly associated with declines in PTS symptoms over time (beta = -0.68). Peer relationship quality at baseline did not moderate baseline or over time associations between witnessing in-home violence and PTS symptoms. The average decline in PTS symptoms due to decreases in witnessing in-home violence and increases in peer relationship quality was 0.51 and 0.65 standard deviations respectively, over the three-year study period. Reducing chronic witnessing in-home violence and promoting the development of healthy social relationships with peers are critical for PTS symptom recovery. PMID- 29793149 TI - Educational and emotional health outcomes in adolescence following maltreatment in early childhood: A population-based study of protective factors. AB - Although childhood maltreatment is associated with long-term impairment, some children function well despite this adversity. This study aimed to identify the key protective factors for good educational attainment and positive emotional health in adolescents who experienced maltreatment in early childhood. Data were analyzed from the Avon Longitudinal Study of Parents and Children, a large UK prospective cohort study. The sample was defined by maternally reported exposure to physical or emotional maltreatment by a parent prior to 5 years. 1118 (8.0%) children were emotionally maltreated and 375 (2.7%) were physically maltreated before the age of 5. There were too few cases of sexual abuse to be considered. Positive outcomes were operationalized as achieving 5 or more grade A*-C GCSE exam grades at 16 years and scores above the cohort median on the self-report Warwick-Edinburgh Mental Wellbeing Scale and Bachmann Self-Esteem Scale at 17.5 years. The associations of individual, family and community covariates with successful adaptation to the adversity of maltreatment were investigated using logistic regression. School related factors, including engagement in extracurricular activities, satisfaction with school and not being bullied were the most important in facilitating resilience in educational attainment, self esteem and wellbeing. Good communication and social skills was the most protective individual trait. There was insufficient evidence to suggest that family factors were associated with resilience to maltreatment. School-based interventions are recommended to promote positive adaptation following parental maltreatment. Future research should evaluate outcomes across the life-course to understand whether the protective influences of school persist into adulthood. PMID- 29793150 TI - Exploring the victimization-early substance misuse relationship: In search of moderating and mediating effects. AB - This study was designed to address two research questions. The first research question asked whether physical abuse victimization at the hands of parents/guardians, bullying victimization at the hands of peers, and the abuse x bullying interaction encouraged early involvement in substance misuse. The second research question inquired as to whether the victimization-substance misuse relationship was mediated by variables proposed by various theories and research studies-specifically, cognitive impulsivity, negative affect, and low self esteem. A moderated mediation hypothesis was tested in a group of 865 (417 boys, 448 girls) schoolchildren from the Illinois Study of Bullying and Sexual Violence who were 10 to 15 years of age at the time of initial contact. A path analysis performed with three waves of data revealed that physical abuse and bullying victimization predicted substance misuse with mediation by cognitive impulsivity, but there was no evidence of moderation. On the basis of these results, it was concluded that victimization, whether through parental physical abuse or peer bullying, increases cognitive impulsivity, and that cognitive impulsivity, in turn, encourages early involvement in substance misuse. The practical implications of these results are that interventions designed to counter cognitive impulsivity and encourage cognitive control may be effective in preventing children traumatized by physical abuse and bullying from entering the early stages of a drug or substance using lifestyle. PMID- 29793151 TI - Effect of two months whole body vibration on hoof growth rate in the horse: A pilot study. AB - Hoof problems are commonly seen in veterinary practice and manipulation of hoof growth rate can be practical and beneficial for that matter. The purpose of this research was to evaluate the effect of whole body vibration (WBV) on hoof growth rate of front feet in the horse. The study was an experimental, single subject, repeated measure design, with all horses serving as control and treatment. Ten horses were subject to WBV, 30 min, twice daily, five days a week, for 60 days in addition to their regular exercise routine. Hoof growth was measured from the reference hairline down to a horizontal groove in both front feet at 30-day (monthly) intervals starting 30 days before the start of treatment (WBV) up until 60 days post cessation of the treatment (WBV). The data analysis was carried out, by applying several paired t-tests to the mean 30-day hoof growth before, during, and after treatment (WBV). A significant mean increase in hoof growth was seen after 30 days WBV (p < 0.001) as well as after 60 days WBV (p = 0.001) with the increase occurring mainly during the first 30 days of WBV. No prolonged effect on hoof growth rate was seen after cessation of WBV. These results indicate that whole body vibration can be used as a non-invasive, safe and non labor-intensive therapeutic modality to accelerate hoof growth in the horse. PMID- 29793152 TI - Identification of seven polyamine oxidase genes in tomato (Solanum lycopersicum L.) and their expression profiles under physiological and various stress conditions. AB - Polyamines (PAs) are implicated in developmental processes and stress responses of plants. Polyamine oxidases (PAOs), flavin adenine dinucleotide-dependent enzymes that function in PA catabolism, play a critical role. Even though PAO gene families of Arabidopsis and rice have been intensely characterized and their expression in response to developmental and environmental changes has been investigated, little is known about PAOs in tomato (Solanum lycopersicum). We found seven PAO genes in S. lycopersicum and named them SlPAO1~7. Plant PAOs form four clades in phylogenetic analysis, of which SlPAO1 belongs to clade-I, SlPAO6 and SlPAO7 to clade-III, and the residual four (SlPAO2~5) to clade-IV, while none belongs to clade-II. All the clade-IV members in tomato also retain the putative peroxisomal-targeting signals in their carboxy termini, suggesting their peroxisome localization. SlPAO1 to SlPAO5 genes consist of 10 exons and 9 introns, while SlPAO6 and SlPAO7 are intronless genes. To address the individual roles of SlPAOs, we analyzed their expression in various tissues and during flowering and fruit development. The expression of SlPAO2~4 was constitutively high, while that of the other SlPAO members was relatively lower. We further analyzed the expressional changes of SlPAOs upon abiotic stresses, oxidative stresses, phytohormone application, and PA application. Based on the data obtained, we discuss the distinctive roles of SlPAOs. PMID- 29793155 TI - Lessons from mosquitoes' painless piercing. AB - Arthropods are the largest group of the living organisms. They attack other organisms by biting, stinging, or piercing and sucking. Among various medically important arthropods, which feed on living hosts, mosquitoes' piercing spread viruses which have been reported to cause the highest number of deaths annually. The primary cause of the deaths is malaria, which is spread by infected mosquitoes' piercing. This study aims at elucidating lessons from mosquitoes' painless piercing. Mosquitoes pierce using their fascicle, which is a bundle of coherently functioning six stylets. Based on experiments and available literature, it is presented that mosquitoes painlessly pierce using a combination of the numbing, the fascicle's serrated design, the vibratory actuation, and the graded and frequency-dependent mechanical properties of the labrum. Based on this understanding, a mosquito-inspired microneedle design has also been proposed. PMID- 29793153 TI - Effects of Mg2+ on recovery of NMDA receptors from inhibition by memantine and ketamine reveal properties of a second site. AB - Memantine and ketamine are NMDA receptor (NMDAR) open channel blockers that are thought to act via similar mechanisms at NMDARs, but exhibit divergent clinical effects. Both drugs act by entering open NMDARs and binding at a site deep within the ion channel (the deep site) at which the endogenous NMDAR channel blocker Mg2+ also binds. Under physiological conditions, Mg2+ increases the IC50s of memantine and ketamine through competition for binding at the deep site. Memantine also can inhibit NMDARs after associating with a second site accessible in the absence of agonist, a process termed second site inhibition (SSI) that is not observed with ketamine. Here we investigated the effects of 1 mM Mg2+ on recovery from inhibition by memantine and ketamine, and on memantine SSI, of the four main diheteromeric NMDAR subtypes. We found that: recovery from memantine inhibition depended strongly on the concentration of memantine used to inhibit the NMDAR response; Mg2+ accelerated recovery from memantine and ketamine inhibition through distinct mechanisms and in an NMDAR subtype-dependent manner; and Mg2+ occupation of the deep site disrupted memantine SSI in a subtype dependent manner. Our results support the hypothesis that memantine associates with, but does not inhibit at the second site. After associating with the second site, memantine can either slowly dissociate directly to the extracellular solution, or transit to the deep site, resulting in typical channel block. Memantine's relatively slow dissociation from the second site underlies the dependence of NMDAR recovery from inhibition on both memantine concentration and on Mg2+. PMID- 29793156 TI - Mechanical properties of the human scalp in tension. AB - Mechanical properties of the human scalp have not been investigated to a great extent with limited information available. The purpose of this study was to provide new baseline material data for human scalp tissue of various ages, which can be applied to experimental and constitutive models, such as in the area of impact biomechanics. This study used specimens from the left and right temporal, fronto-parietal and occipital regions of the human scalp. It investigated the tensile behavior of scalp tissue using tissues harvested from unfixed, fresh cadavers. These samples were subjected to an osmotic stress analysis and upon testing, cyclic loading followed by stretching until failure in a universal testing machine. Strain evaluation was conducted using digital image correlation in a highly standardized approach. Elastic modulus, tensile strength, strain at maximum load and strain to failure were evaluated computationally. No significant differences were observed comparing the tensile strength between males and females. In contrast to that, a sex-dependent difference was found for the elastic modulus of the occipital scalp region and for the elongation properties. Additionally, regional differences within the male group, as well as an age dependent correlation for females were found in the elastic modulus and tensile strength. Scanning electron microscope analyses have shown the ultrastructural failure patterns, indicated by damaged keratin plates, as well as partially disrupted and retraced collagens at the failure site. The novel data obtained in this study could add valuable information to be used for modeling purposes, as well as provide baseline data for simulant materials and comparisons of tissue properties following head injury or forensic investigations. PMID- 29793154 TI - Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3beta. AB - Prodromal memory deficits represent an important marker for the development of schizophrenia (SZ), in which glutamatergic hypofunction occurs in the prefrontal cortex (PFC). The mGluR2/3 agonist LY379268 (LY37) attenuates excitatory N-methyl D-aspartate receptor (NMDAR)-induced neurotoxicity, a central pathological characteristic of glutamatergic hypofunction. We therefore hypothesized that early treatment with LY37 would rescue cognitive deficits and confer benefits for SZ-like behaviors in adults. To test this, we assessed whether early intervention with LY37 would improve learning outcomes in the Morris Water Maze for rats prenatally exposed to methylazoxymethanol acetate (MAM), a neurodevelopmental SZ model. We found that a medium dose of LY37 prevents learning deficits in MAM rats. These effects were mediated through postsynaptic mGluR2/3 via improving GluN2B-NMDAR function by inhibiting glycogen synthase kinase-3beta (GSK3beta). Furthermore, dendritic spine loss and learning and memory deficits observed in adult MAM rats were restored by juvenile LY37 treatment, which did not change prefrontal neuronal excitability and glutamatergic synaptic transmission in adult normal rats. Our results provide a mechanism for mGluR2/3 agonists against NMDAR hypofunction, which may prove to be beneficial in the prophylactic treatment of SZ. PMID- 29793158 TI - Botulinum toxin type-A affects mechanics of non-injected antagonistic rat muscles. AB - Botulinum toxin type A (BTX-A) effects on the mechanics of non-injected antagonistic muscles are unknown. The aim was to test the following hypotheses in a rat model: BTX-A injected into gastrocnemius medialis (GM) and lateralis (GL) (1) decreases forces of the antagonistic tibialis anterior (TA) and extensor digitorum longus (EDL), (2) reduces length range of force exertion and (3) increases passive forces of the TA, and (4) changes inter-antagonistic and inter synergistic epimuscular myofascial force transmission (EMFT). Two groups of Wistar rats were tested: BTX (0.1 units of BTX-A were injected to the GM and GL, each) and Control (saline injected). Five-days post, TA, EDL, GM-GL, and soleus distal and EDL proximal isometric forces were measured after TA lengthening. BTX A exposure caused forces of all muscles to decrease significantly. TA and EDL active force drops (maximally by 37.3%) show inter-compartmental spread. Length range of force exertion of the TA did not change, but its passive force increased significantly (by 25%). The percentages of intramuscular connective tissue content of the TA and EDL was higher (BTX: 20.0 +/- 4.9% and 19.3 +/- 4.1% vs. control: 13.1 +/- 5.4% and 14.5 +/- 4.0%, respectively). Calf muscles' forces were not affected by TA length changes for both groups indicating lacking inter antagonistic EMFT. However, BTX-A altered EDL proximo-distal force differences hence, inter-synergistic EMFT. A major novel finding is that BTX-A affects mechanics of non-injected antagonistic muscles in test conditions involving only limited EMFT. The effects indicating a stiffer muscle with no length range increase contradict some treatment aims, which require clinical testing. PMID- 29793157 TI - Energy dissipation in quasi-linear viscoelastic tissues, cells, and extracellular matrix. AB - Characterizing how a tissue's constituents give rise to its viscoelasticity is important for uncovering how hidden timescales underlie multiscale biomechanics. These constituents are viscoelastic in nature, and their mechanics must typically be assessed from the uniaxial behavior of a tissue. Confounding the challenge is that tissue viscoelasticity is typically associated with nonlinear elastic responses. Here, we experimentally assessed how fibroblasts and extracellular matrix (ECM) within engineered tissue constructs give rise to the nonlinear viscoelastic responses of a tissue. We applied a constant strain rate, "triangular-wave" loading and interpreted responses using the Fung quasi-linear viscoelastic (QLV) material model. Although the Fung QLV model has several well known weaknesses, it was well suited to the behaviors of the tissue constructs, cells, and ECM tested. Cells showed relatively high damping over certain loading frequency ranges. Analysis revealed that, even in cases where the Fung QLV model provided an excellent fit to data, the the time constant derived from the model was not in general a material parameter. Results have implications for design of protocols for the mechanical characterization of biological materials, and for the mechanobiology of cells within viscoelastic tissues. PMID- 29793159 TI - Impacts of groundwater management on energy resources and greenhouse gas emissions in California. AB - California faces significant energy and water infrastructure planning challenges in response to a changing climate. Immediately following the most severe recorded drought, the state experienced one of its wettest water years in recorded history. Despite the recent severe wet weather, much of the state's critical groundwater systems have not recovered from the drought. The recent Sustainable Groundwater Management Act (SGMA) aims to eliminate future depletion risks, but may force California basins to seek alternative water sources by limiting groundwater withdrawals during droughts. These alternative water resources, such as recycled water or desalination, can have significantly higher energy demands in treatment and supply than local groundwater or surface water resources. This research developed potential scenarios of water supply sources for five overdrafted groundwater basins, and modeled the impacts of these scenarios on energy demands and greenhouse gas (GHG) emissions for water supply systems. Our results reveal that energy demands and GHG emissions in different water supply scenarios can vary substantially between basins, but could increase statewide energy consumption as much as 2% and GHG emissions by 0.5. These results highlight the need to integrate these energy and GHG impacts into water resource management. Better understanding these considerations enables water supply planners to avoid potential unintended consequences (i.e., increased energy demands and GHG emissions) of enhancing drought resilience. PMID- 29793160 TI - Water footprint characteristic of less developed water-rich regions: Case of Yunnan, China. AB - Rapid industrialization and urbanization pose pressure on water resources in China. Virtual water trade proves to be an increasingly useful tool in water stress alleviation for water-scarce regions, while bringing opportunities and challenges for less developed water-rich regions. In this study, Yunnan, a typical province in southwest China, was selected as the case study area to explore its potential in socio-economic development in the context of water sustainability. Both input-output analysis and structural decomposition analysis on Yunnan's water footprint for the period of 2002-2012 were performed at not only an aggregated level but also a sectoral level. Results show that although the virtual water content of all economic sectors decreased due to technological progress, Yunnan's total water footprint still increased as a result of economic scale expansion. From the sectoral perspective, sectors with large water footprints include construction sector, agriculture sector, food manufacturing & processing sector, and service sector, while metal products sector and food manufacturing & processing sector were the major virtual water exporters, and textile & clothing sector and construction sector were the major importers. Based on local conditions, policy suggestions were proposed, including economic structure and efficiency optimization, technology promotion and appropriate virtual water trade scheme. This study provides valuable insights for regions facing "resource curse" by exploring potential socio-economic progress while ensuring water security. PMID- 29793161 TI - Exposure of Microcystis aeruginosa to hydrogen peroxide and titanium dioxide under visible light conditions: Modeling the impact of hydrogen peroxide and hydroxyl radical on cell rupture and microcystin degradation. AB - The aims of this study are to evaluate, under visible light conditions, the ability of H2O2 and TiO2 to produce OH, their quantitative impacts on the cell integrity of Microcystis, and the subsequent release and degradation of microcystins (MCs). A sequential reaction model was developed, including one sub model to simulate the rupture kinetics for cell integrity of Microcystis, and another to describe the release and degradation of MCs. For cell rupture, the dual-oxidant Delayed Chick-Watson model (DCWM) and dual-oxidant Hom model (HM) were first proposed and developed, giving excellent simulation results of cell rupture kinetics. Kinetic rate constants between Microcystis cells and H2O2 [Formula: see text] as well as OH (k*OH, Cell) under visible light successfully separated the individual effects of H2O2 and OH on Microcystis. The dual-oxidant models were further validated with additional experiments, making the models more convincing. Finally, the dual-oxidant cell rupture models were integrated with the MC degradation model and well predicted the observed MCs concentrations in the experimental systems. The results of this study not only demonstrate the potential application of H2O2 and TiO2 for the control of cyanobacteria and metabolites in natural water bodies, but also provide a new methodology to differentiate the individual contributions of the two oxidants, H2O2 and OH, on cell rupture, thus giving a novel way to more precisely determine the effective doses of applied oxidants for cyanobacteria control. PMID- 29793163 TI - Rheological characterisation of concentrated domestic slurry. AB - The much over-looked element in new sanitation, the transport systems which bridge the source and treatment facilities, is the focus of this study. The knowledge of rheological properties of concentrated domestic slurry is essential for the design of the waste collection and transport systems. To investigate these properties, samples were collected from a pilot sanitation system in the Netherlands. Two types of slurries were examined: black water (consisting of human faecal waste, urine, and flushed water from vacuum toilets) and black water with ground kitchen waste. Rheograms of these slurries were obtained using a narrow gap rotating rheometer and modelled using a Herschel-Bulkley model. The effect of concentration on the slurry are described through the changes in the parameters of the Herschel-Bulkley model. A detailed method is proposed on estimating the parameters for the rheological models. For the black water, yield stress and consistency index follow an increasing power law with the concentration and the behaviour index follows a decreasing power law. The influence of temperature on the viscosity of the slurry is described using an Arrhenius type relation. The viscosity of black water decreases with temperature. As for the black water mixed with ground kitchen waste, it is found that the viscosity increases with concentration and decreases with temperature. The viscosity of black-water with ground kitchen waste is found to be higher than that of black water, which can be attributed to the presence of larger particles in the slurry. PMID- 29793162 TI - New insights into the formation of silver-based nanoparticles under natural and semi-natural conditions. AB - For the first time, the natural formation of silver-based nanoparticles (Ag-b NPs) was studied in field investigations of two pre-alpine lakes in Germany that contain geogenic silver traces in the sub-ng L-1 range. Light-sensitive microorganisms most likely accumulate and transport these silver traces from deeper water layers to the surface. At the surface of the eutrophic lake, approximately 40% of total silver (5.7 ng L-1) consisted of Ag-b-NPs, whereas in the oligotrophic lake with similar enrichment of silver species, no Ag-b-NPs were detected. Additional lab experiments with nature-related Ag(I) concentrations in the lower-ng L-1 range and natural organic matter with total organic carbon values of <=5 mg L-1 revealed that, contrary to common interpretation in the literature, Ag-b-NPs are also or even preferably formed in the dark. Particle size increases gradually with increasing reaction time, showing that Ostwald ripening occurs even at such low particle concentrations. When sulfide ions are present, smaller Ag-b-NPs with a narrower size distribution are formed. PMID- 29793164 TI - Childhood socioeconomic status and longitudinal patterns of alcohol problems: Variation across etiological pathways in genetic risk. AB - Childhood socioeconomic status (SES) is an important aspect of early life environment associated with later life health/health behaviors, including alcohol misuse. However, alcohol misuse is modestly heritable and involves differing etiological pathways. Externalizing disorders show significant genetic overlap with substance use, suggesting an impulsivity pathway to alcohol misuse. Alcohol misuse also overlaps with internalizing disorders, suggesting alcohol is used to cope. These differing pathways could lead to different patterns over time and/or differential susceptibility to environmental conditions, such as childhood SES. We examine whether: 1) genetic risk for externalizing and internalizing disorders influence trajectories of alcohol problems across adolescence to adulthood, 2) childhood SES alters genetic risk these disorders on trajectories of alcohol problems, and 3) these patterns are consistent across sex. We find modest evidence of gene-environment interaction. Higher childhood SES increases the risk of alcohol problems in late adolescence/early adulthood, while lower childhood SES increases the risk of alcohol problems in later adulthood, but only among males at greater genetic risk of externalizing disorders. Females from lower SES families with higher genetic risk of internalizing or externalizing disorders have greater risk of developing alcohol problems. PMID- 29793165 TI - Inhibition of acetaminophen-induced hepatotoxicity in mice by exogenous thymosinbeta4 treatment. AB - OBJECTIVE: To study the effects of exogenous thymosinbeta4 (Tbeta4) treatment in acetaminophen (APAP)-induced hepatotoxicity. METHODS: Liver injury was induced in mice by a single intraperitoneal injection of APAP (500 mg/kg). Exogenous Tbeta4 was intraperitoneally administrated at 0 h, 2 h and 4 h after APAP injection. Chloroquine (CQ) (60 mg/kg) was intraperitoneally injected 2 h before APAP administration to inhibit autophagy. Six hours after APAP injection liver injury was evaluated by histological examinations, biochemical measurements and enzyme linked immunosorbent assay (ELISAs). Western blots were performed to detect proteins expression. RESULTS: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly increased 6 h after APAP administration, but were significantly reduced by co-administration of Tbeta4. Histological examinations demonstrated that Tbeta4 reduced necrosis and inflammation induced by APAP. Immunofluorescence showed that Tbeta4 suppressed APAP-induced translocation of high mobility group box-1 protein (HMGB1) from the nucleus to cytosol and intercellular space. Hepatic glutathione (GSH) depletion, malondialdehyde (MDA) formation and decreased superoxide dismutase (SOD) activities induced by APAP were all attenuated by Tbeta4. APAP-induced increases in hepatic nuclear factor-kappaB (NF-kappaB) p65 protein expression and inflammatory cytokines production including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were reduced by Tbeta4 treatment. Increased LC3 and p62 proteins in the liver tissues of APAP-treated mice were decreased by Tbeta4 treatment, which indicated the enhancement of autophagy flux by Tbeta4. Furthermore, inhibiting autophagy by CQ abrogated the protective effects of Tbeta4 against APAP hepatotoxicity. CONCLUSION: Exogenous Tbeta4 treatment exerts protective effects against APAP-induced hepatotoxicity in mice. The underneath molecular mechanisms may involve autophagy enhancement and inhibition of oxidative stress by Tbeta4. PMID- 29793166 TI - Renoprotective effect of the isoflavonoid biochanin A against cisplatin induced acute kidney injury in mice: Effect on inflammatory burden and p53 apoptosis. AB - Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen. Further, renal homogenates showed increased level of inflammatory cytokines and upregulation of the expression of p53 up regulated modulator of apoptosis (PUMA), p53 and caspase 3 but downregulation in Nrf2 expression. Furthermore, cisplatin group showed marked necrosis and degenerated tubular lining epithelial cells with frequently detected apoptotic bodies. Mice treated with biochanin A (10, 20 or 40 mg/kg) for 14 days prior to cisplatin abrogated cisplatin-mediated damage. Furthermore, the elevated serum creatinine and urea levels were lessened by some doses of biochanin A, indicating protection against renal injury. Similarly, the changes in apoptosis and inflammatory markers have ameliorated to significant levels (P < 0.05). The results suggest biochanin A as a nephroprotective agent against cisplatin toxicity. Overall, this nephroprotective effect of biochanin A involved anti inflammatory and antiapoptotic activities. PMID- 29793169 TI - Spontaneous rise in open rectangular channels under gravity. AB - Fluid movement in microfluidic devices, porous media, and textured surfaces involves coupled flows over the faces and corners of the media. Spontaneous wetting of simple grooved surfaces provides a model system to probe these flows. This numerical study investigates the spontaneous rise of a liquid in an array of open rectangular channels under gravity, using the Volume-of-Fluid method with adaptive mesh refinement. The rise is characterized by the meniscus height at the channel center, outer face and the interior and exterior corners. At lower contact angles and higher channel aspect ratios, the statics and dynamics of the rise in the channel center show little deviation with the classical model for capillarity, which ignores the existence of corners. For contact angles smaller than 45 degrees , rivulets are formed in the interior corners and a cusp at the exterior corner. The rivulets at long times obey the one-third power law in time, with a weak dependence on the geometry. The cusp behaviour at the exterior corner transforms into a smooth meniscus when the capillary force is higher in the channel, even for contact angles smaller than 45 degrees . The width of the outer face does not influence the capillary rise inside the channel, and the channel size does not influence the rise on the outer face. PMID- 29793167 TI - Improvement of neuronal differentiation by carbon monoxide: Role of pentose phosphate pathway. AB - Over the last decades, the silent-killer carbon monoxide (CO) has been shown to also be an endogenous cytoprotective molecule able to inhibit cell death and modulate mitochondrial metabolism. Neuronal metabolism is mostly oxidative and neurons also use glucose for maintaining their anti-oxidant status by generation of reduced glutathione (GSH) via the pentose-phosphate pathway (PPP). It is established that neuronal differentiation depends on reactive oxygen species (ROS) generation and signalling, however there is a lack of information about modulation of the PPP during adult neurogenesis. Thus, the main goal of this study was to unravel the role of CO on cell metabolism during neuronal differentiation, particularly by targeting PPP flux and GSH levels as anti oxidant system. A human neuroblastoma SH-S5Y5 cell line was used, which differentiates into post-mitotic neurons by treatment with retinoic acid (RA), supplemented or not with CO-releasing molecule-A1 (CORM-A1). SH-SY5Y cell differentiation supplemented with CORM-A1 prompted an increase in neuronal yield production. It did, however, not alter glycolytic metabolism, but increased the PPP. In fact, CORM-A1 treatment stimulated (i) mRNA expression of 6 phosphogluconate dehydrogenase (PGDH) and transketolase (TKT), which are enzymes for oxidative and non-oxidative phases of the PPP, respectively and (ii) protein expression and activity of glucose 6-phosphate dehydrogenase (G6PD) the rate limiting enzyme of the PPP. Likewise, whenever G6PD was knocked-down CO-induced improvement on neuronal differentiation was reverted, while pharmacological inhibition of GSH synthesis did not change CO's effect on the improvement of neuronal differentiation. Both results indicate the key role of PPP in CO modulation of neuronal differentiation. Furthermore, at the end of SH-SY5Y neuronal differentiation process, CORM-A1 supplementation increased the ratio of reduced and oxidized glutathione (GSH/GSSG) without alteration of GSH metabolism. These data corroborate with PPP stimulation. In conclusion, CO improves neuronal differentiation of SH-S5Y5 cells by stimulating the PPP and modulating the GSH system. PMID- 29793170 TI - Effective size selection of MoS2 nanosheets by a novel liquid cascade centrifugation: Influences of the flakes dimensions on electrochemical and photoelectrochemical applications. AB - Although liquid phase exfoliation is a powerful method to produce MoS2 nanosheets in large scale, but its effectiveness is limited by the diversity of produced nanosheets sizes. Here a novel approach for separation of MoS2 flakes having various lateral sizes and thicknesses based on the cascaded centrifugation has been introduced. This method involves a pre-separation step which is performed through low-speed centrifugation to avoid the deposition of large area single and few-layers by the heavier particles. The bulk MoS2 powders were dispersed in an aqueous solution of sodium cholate (SC) and sonicated for 12 h. The main separation step was performed using different speed centrifugation intervals of 10-11, 8-10, 6-8, 4-6, 2-4 and 0.5-2 krpm by which nanosheets containing 2, 4, 7, 8, 14, 18 and 29 layers were obtained respectively. The samples were characterized using XRD, FESEM, AFM, TEM, DLS and also UV-vis, Raman and PL spectroscopy measurements. Dynamic light scattering (DLS) measurements have confirmed the existence of a larger number of single or few-layers MoS2 nanosheets compared to when the pre-separation step was not used. Finally, Photocurrent and cyclic voltammetry of different samples were measured and found that the flakes with bigger surface area had larger CV loop area. Our results provide a method for the preparation of a MoS2 monolayer enriched suspension which can be used for different applications. PMID- 29793168 TI - Olive oil polyphenols reduce oxysterols -induced redox imbalance and pro inflammatory response in intestinal cells. AB - Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases. In the present study we evaluated the ability of an extra virgin olive oil phenolic extract to counteract the pro-oxidant and pro-inflammatory action of a representative mixture of dietary oxysterols in the human colon adenocarcinoma cell line (Caco-2) undergoing full differentiation into enterocyte-like cells. Oxysterols treatment significantly altered differentiated Caco-2 cells redox status, leading to oxidant species production and a decrease of GSH levels, after 1 h exposure, followed by an increase of cytokines production, IL-6 and IL-8, after 24 h. Oxysterol cell treatment also induced after 48 h an increase of NO release, due to the induction of iNOS. Pretreatment with the phenolic extract counteracted oxysterols effects, at least in part by modulating one of the main pathways activated in the cellular response to the action of oxysterols, the MAPK NF-kB pathway. We demonstrated the ability of the phenolic extract to directly modulate p38 and JNK1/2 phosphorylation and activation of NF-kB, following its inhibitor IkB phosphorylation. The phenolic extract also inhibited iNOS induction, keeping NO concentration at the control level. Our results suggest a protective effect at intestinal level of extra virgin olive oil polyphenols, able to prevent or limit redox unbalance and the onset and progression of chronic intestinal inflammation. PMID- 29793171 TI - Compositional engineering of acceptors for highly efficient bulk heterojunction hybrid organic solar cells. AB - The wet chemical synthesis of chromium oxide (Cr2O3) nanoparticles (NPs) and its application in active layer of inverted bulk heterojunction organic solar cells is documented in this research. Chromium oxide NPs of 10-30 nm size range having a band gap of 2.9 eV were successfully synthesized. These NPs were used in inverted organic solar cells in amalgamation with P3HT:PCBM and PTB7:PCBM polymers. The fabricated hybrid devices improves PCE significantly for P3HT:PCBM and PTB7:PCBM systems. The photophysical energy levels, optoelectrical properties and microscopic images have been systematically studied for the fabricated devices. The introduction of Cr2O3 nanoparticles (NPs) enhances light harvesting and tunes energy levels into improved electrical parameters. A clear red shift and improved absorption have been observed for ternary blended devices compared to that observed with controlled organic solar cells. Apparently, when the amount of NPs in the binary polymer blend exceeds the required optimum level, there is a breakdown of the bulk heterojunction leading to lowering of the optical and electrical performance of the devices. PMID- 29793173 TI - Ag nanoparticles loading of polypyrrole-coated superwetting mesh for on-demand separation of oil-water mixtures and catalytic reduction of aromatic dyes. AB - Herein, a catalytic mesh with unique wettability, high oil-water separation efficiency and excellent catalytic performance towards aromatic dyes was fabricated. Polypyrrole (PPy) was firstly pre-coated on pristine stainless-steel mesh (SSM) surface via cyclic voltammetry approach. Subsequently, a simple electrodeposition process was performed to prepare and anchor Ag nanoparticles (AgNPs) onto the PPy-coated SSM surface. The PPy-coated mesh with anchored AgNPs was denoted as PPy/AgNPs-coated SSM. The obtained PPy/AgNPs-coated SSM exhibited dual superlyophobic properties and were able to achieve on-demand separation to deal with various of light oil (rhooil < rhowater) and heavy oil (rhooil > rhowater)-water mixtures. Importantly, benefitting from AgNPs on mesh surface, the obtained PPy/AgNPs-coated SSM exhibits exceptional catalytic activity. As proof-of-concept three typical aromatic dye molecules (methylene blue, rhodamine B and Congo red) can be effectivity degraded. Additionally, the degradation of aromatic dyes and oil-water separation were achieved simultaneously when the PPy/AgNPs-coated SSM was converted to water-removing mode. Therefore, the present work is of great significance to the development of novel oil-water filtration membranes and can open a new avenue towards the practicability of metal nanoparticle catalysts in wastewater treatment. PMID- 29793172 TI - On the autonomous motion of active drops or bubbles. AB - Thermo-capillary stresses on the surface of a drop can be the result of a non isothermal surface chemical conversion of a reactant dissolved in the host fluid. The strength of heat production (with e.g. absorption) on the surface is ruled by the diffusion of the reactant and depends on the state of motion of the drop. Such thermo-capillary stresses can provoke the motion of the drop or its motionless state in the presence of an external body force. If in the balance of forces, including indeed viscous drag, the net resultant force vanishes there is the possibility of autonomous motion with constant velocity of the drop. Focusing on drops with radii in the millimeter range provided here is a quantitative study of the possibility of such autonomous motion when the drop, considered as active unit, is seat of endo- or exo-thermic reactive processes that dominate its motion. The framework is restricted to Stokes flows in the hydrodynamics, negligible heat Peclet number while the solute Peclet number is considered very high. A boundary layer approximation is used in the description of reactant diffusion. Those processes eventually end up in the action being expressed by surface tension gradients and the Marangoni effect. Explicit expressions of the force acting on the drop and the velocity fields inside and outside the drop are provided. Some significant particular cases are discussed to illustrate the usefulness of the theory. PMID- 29793174 TI - Effect of Ca2+ ion concentration on adsorption of poly(carboxylate ether)-based (PCE) superplasticizer on mica. AB - HYPOTHESIS: Poly(carboxylate ether)-based (PCE) superplasticizers consist of a carboxylic acid backbone and grafted poly(ethylene glycol) (PEG) side chains. Ca2+ ion bridging mechanism is commonly purported to control PCE's adsorption on negatively charged cement particle surfaces in cement suspension, thus PCE was expected to adsorb on negatively charged surfaces in synthetic pore solutions via Ca2+/COO- interactions. EXPERIMENTS: Adsorption behaviors of a commercial PCE on negatively charged mica were studied in aqueous electrolyte solutions by a surface forces apparatus. FINDINGS: Direct force measurements indicated that the PCE adsorbed onto mica from 0.1 M K2SO4 due to K+ ion chelation by the ether oxygen units CH2CH2O on the PEG chains, but surprisingly did not adsorb from either 0.1 M K2SO4 with saturated Ca(OH)2 or 0.1 M Ca(NO3)2. The adsorption in K2SO4 was weak, enabling the adsorbed PCE layers to be squeezed out under modest compression. Upon separating the surfaces, the PCE immediately achieved an identical re-adsorption. In high-calcium conditions, the PCE was highly positively charged due to Ca2+ ion chelation by PEG chains and backbone carboxylic groups COO-, and mica also underwent charge reversal due to electrostatic adsorption/binding of Ca2+ ions. Consequently, the interaction between mica and PCE was electrostatically repulsive and no PCE adsorption occurred. These findings can be explained by the complex interplay of ion chelation by PEG chains, electrostatic binding and screening interactions with charged surfaces in the presence of monovalent and divalent counterions, and ultimately charge reversal of both the charged surfaces and polyelectrolyte in high divalent ion conditions. PMID- 29793175 TI - Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes. AB - BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin 15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5 year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score. PMID- 29793176 TI - Non-LDL dyslipidemia is prevalent in the young and determined by lifestyle factors and age: The LifeLines cohort. AB - BACKGROUND AND AIMS: Non-LDL dyslipidemia (NLD) confers cardiovascular risk, and prevalence rates appear to be high in elderly populations. Small cohorts have identified several lifestyle, anthropometric, and medical factors associated with NLD. We aimed to assess sex- and age-specific prevalence of NLD in a contemporary population cohort (n = 167 729), and to identify independent determinants of NLD, focusing on lifestyle, anthropometric, and medical factors. METHODS: The prevalence of NLD was assessed per 10-year age intervals in adults without cardiovascular disease not using lipid-modifying drugs from the Dutch LifeLines cohort. NLD was defined as low HDL-cholesterol or high triglycerides or high remnant cholesterol as per guideline cut-off values. Multivariable regression was used to identify factors independently associated with NLD. Determinants included age, smoking, alcohol use, physical activity, diet, BMI, diabetes mellitus (DM), chronic kidney disease, and in women, menopausal state and oral contraceptive use. RESULTS: NLD occurred in 15-19% of women and 13-30% of men in this cohort, with the highest prevalence of 30% in 35-55 year old men. In most age groups, the prevalence in women was lower than in men. Obesity (both sexes: Odds ratio (OR) 5.3, 95% confidence interval (95%CI) 5.0-5.7), current smoking (men: OR 1.8, 95%CI 1.7-1.9; women OR 2.2, 95%CI 2.1-2.3), and DM (men: OR 2.2, 95%CI 1.8-2.6; women: OR 2.7, 95%CI 2.3-3.1) were strongly associated with NLD. CONCLUSIONS: NLD already occurs frequently at an early age. Modifiable lifestyle choices, obesity, and DM were strong determinants of NLD. Public health efforts could substantially contribute to decrease NLD. PMID- 29793178 TI - Nrf2/P-glycoprotein axis is associated with clinicopathological characteristics in colorectal cancer. AB - Colorectal cancer (CRC) is the fourth leading cause of cancer-related death worldwide. Activation of ABCB1 gene and its main product, P-glycoprotein, is the common reason for chemoresistance. The nuclear factor-erythroid 2-related factor2 (Nrf2) is directly regulated by Kelch like ECH-associated protein1 (Keap1). In addition, Nrf2 is a key transcriptional factor that regulates efflux transporters, including P-gp. The aim of this study was to investigate the expression levels of Nrf2, Keap1 and ABCB1 in the biopsy samples and their association with clinicopathological features in CRC patients. Both mRNA and protein expression levels were measured by Real-time PCR and immunohistochemistry (IHC), respectively, in biopsies from colonoscopy in 65 CRC patients compared to those in 65 non-CRC individuals. While expression levels of Nrf2 and ABCB1 (P-gp) were markedly higher in both mRNA and protein levels in CRC biopsies (p < 0.01), Keap1 expression level was significantly lower in these samples (p < 0.05). Positive correlations between Nrf2 expression level and tumor size (p = 0.003), lymph node (p = 0.038), distant metastasis (p = 0.008), and smoking status (p = 0.02) were observed. However, P-gp expression was associated only with patient age and smoking status. In addition, there was a positive correlation between protein levels of Nrf2 and P-gp, in both CRC (r = 0.617, p < 0.001) and non-CRC tissues (r = 0.930, p < 0.001). In conclusion, over-expression of Nrf2 and ABCB1/P-gp, as well as down-regulation of mRNA expression level of Keap1 in CRC patients denotes the role of Keap1/Nrf2/ABCB1 axis in CRC progression and chemoresistance. Our data suggest that therapeutic inhibition of Nrf2/ABCB1 signaling can be considered as a novel strategy to improve the efficacy of chemotherapeutics against CRC. PMID- 29793177 TI - Long noncoding RNA GAS5 suppresses triple negative breast cancer progression through inhibition of proliferation and invasion by competitively binding miR 196a-5p. AB - Triple-negative breast cancer (TNBC) is considered to be the most aggressive and lethal type of breast cancer. Many studies have suggested that the dysfunction of long noncoding RNAs (lncRNAs) is correlated with breast cancer metastasis and progression. Here, we show that levels of the lncRNA, growth arrest-specific transcript 5 (GAS5), are decreased in TNBC tissues, and this down-regulation of GAS5 is associated with an aggressive tumor phenotype in patients, affecting clinical stage, lymph node metastasis and overall survival. Using an ectopic overexpression system in TNBC cells, we found that up-regulation of GAS5 can significantly attenuate proliferation and enhance apoptosis in TNBC cells. Through bioinformatics analysis and verification with qRT-PCR and luciferase assay, we found that GAS5 can bind to miR-196a-5p and there is a negative relationship between GAS5 and miR-196a-5p expression among TNBC patient samples. Furthermore, we demonstrated that overexpression of GAS5 can partially undermine the tumor promotion effect induced by ectopic expression of miR-196a-5p, including invasion and downstream FOXO1/PI3K/AKT signal pathway activation. In our study, GAS5 functioned as a competing endogenous RNA (ceRNA) antagonizing tumor promotion of miR-196a-5p-expressing TNBC cells. These data suggest that GAS5 can suppress TNBC progression by competitively binding miR-196a-5p, therefore GAS5 may be a prognostic biomarker of TNBC. PMID- 29793179 TI - Nano strategies for berberine delivery, a natural alkaloid of Berberis. AB - Berberine, as a phytochemical component of some medicinal Chinese herbs (most frequently Berberis vulgaris), is an isoquinoline alkaloid with many therapeutic effects including anti-viral, anti-microbial, anti-diarrhea, anti-inflammatory and anti-tumor effects. Berberine has some significant effects on type 2 diabetes through adenosine monophosphate-activated protein kinase activation, glycolysis stimulation, and mitochondrial function inhibition which subsequently improves both lipid and glucose metabolism. Some other effects of berberine on congestive heart failure, cardiac arrhythmia and hypertension have been reported. Beside the beneficial effects of berberine, some limitations including poor aqueous solubility, slight absorption, and low bioavailability have hindered its applications. To overcome these limitations, nanotechnology has been considered as main strategy. This review describes different types of nanocarriers (polymeric based, magnetic mesoporous silica based, lipid based, dendrimer based, graphene based, silver and gold nanoparticles) have been used for encapsulation of berberine. PMID- 29793180 TI - Insulin is a potential antioxidant for diabetes-associated cognitive decline via regulating Nrf2 dependent antioxidant enzymes. AB - PURPOSE: To investigate the neuroprotective effects of insulin on diabetic encephalopathy and its mechanism. EXPERIMENTAL AND APPROACH: The diabetic model was established by injection of streptozotocin. Behavior examinations were conducted by the Morris water maze. Histopathological alterations were detected by HE staining. ROS, CAT levels and SOD activity were measured using a microplate reader. In vitro, the viability of wild type and knock-down PC12 cells was detected by MTT assay, the morphology of cells was monitored under a microscope. The subcellular distribution of Nrf2 was observed by western blotting and immunohistochemistry. KEY RESULTS: Evident oxidative stress injury was observed in diabetic rats and H2O2-induced PC12 cells. Insulin not only protect diabetic rat from oxidative stress injury but also significantly inhibited H2O2-induced apoptosis and intracellular ROS in cells. In addition, the level of malondialdehyde was reduced, and the activities of superoxide dismutase, catalase and glutathione peroxidase were augmented in both diabetic rats and PC12 cells. Interestingly, insulin promoted the translocation of Nrf2 into the nucleus and activation of downstream antioxidant protein expression. Further, the Nrf2 knockdown cells suffered more serious H2O2-induced damage than the wild PC12 cells. Moreover, insulin had no significant protective effect on knockdown cells with H2O2-damage. CONCLUSION AND IMPLICATIONS: Collectively, our results suggested that insulin significantly inhibited neuronal damage through the Nrf2 signaling pathway, which regulates endogenous oxidant-antioxidant balance, therefore, insulin may be a potential protective agent for the treatment of oxidative stress-induced diabetic encephalopathy. PMID- 29793181 TI - Exogenously applied spermidine alleviates photosynthetic inhibition under drought stress in maize (Zea mays L.) seedlings associated with changes in endogenous polyamines and phytohormones. AB - Drought stress (DS) is a major environmental factor limiting plant growth and crop productivity worldwide. It has been established that exogenous spermidine (Spd) stimulates plant tolerance to DS. The effects of exogenous Spd on plant growth, photosynthetic performance, and chloroplast ultrastructure as well as changes in endogenous polyamines (PAs) and phytohormones were investigate in DS resistant (Xianyu 335) and DS-sensitive (Fenghe 1) maize seedlings under well watered and DS treatments. Exogenous Spd alleviated the stress-induced reduction in growth, photosynthetic pigment content, photosynthesis rate (Pn) and photochemical quenching (qP) parameters, including the maximum photochemistry efficiency of photosystem II (PSII) (Fv/Fm), PSII operating efficiency (FPSII), and qP coefficient. Exogenous Spd further enhanced stress-induced elevation in non-photochemical quenching (NPQ) and the de-epoxidation state of the xanthophyll cycle (DEPS). Microscopic analysis revealed that seedlings displayed a more ordered arrangement of chloroplast ultrastructure upon Spd application during DS. Exogenous Spd increased the endogenous PA concentrations in the stressed plants. Additionally, exogenous Spd increased indoleacetic acid (IAA), zeatin riboside (ZR) and gibberellin A3 (GA3) and decreased salicylic acid (SA) and jasmonate (JA) concentrations under DS. These results indicate that exogenous Spd can alleviate the growth inhibition and damage to the structure and function of the photosynthetic apparatus caused by DS and that this alleviation may be associated with changes in endogenous PAs and phytohormones. This study contributes to advances in the knowledge of Spd-induced drought tolerance. PMID- 29793182 TI - Healthcare provider counseling to quit smoking and patient desire to quit: The role of negative smoking outcome expectancies. AB - AIMS: The U.S. Public Health Service Clinical Practice Guideline on treating tobacco use and dependence recommends providing advice to quit to every tobacco user seen in a healthcare setting. However, the mechanism through which counseling encourages patients to quit has not been adequately studied. This study tests whether the association between receiving healthcare provider counseling and desire to quit is accounted for by negative health and psychosocial outcome expectancies of smoking. METHODS: Data were collected online from 721 adult smokers who had seen a healthcare provider in the past 12 months. Associations between counseling to quit, negative outcome expectancies of smoking, and desire to quit were tested, as well as whether outcome expectancies and desire to quit differed by type of counseling (counseling only vs. counseling plus assistance) and level of smoking. RESULTS: Bivariate associations indicated a stronger desire to quit among patients receiving counseling, particularly when it included healthcare provider assistance to quit. SEM results indicated that the association between counseling and desire to quit was fully accounted for by patients' negative health and psychosocial outcome expectancies for smoking. These associations were found across levels of smoking in the case of health expectancies, but were limited to moderate and heavy smokers in the case of psychosocial expectancies. CONCLUSION: Results suggest that the time devoted to counseling patients about smoking should include providing some assistance to quit, such as recommending a product, prescription or program. Regardless of smoking level, this counseling should incorporate techniques to elicit patients' negative health and psychosocial expectancies of smoking. PMID- 29793184 TI - An actigraphic study of the sleep patterns of younger and older school-age children. AB - OBJECTIVE: Sleep is viewed as being relatively consistent across the school-age period (6-13 years of age), however this claim has not been empirically supported. The objective of this study was to document the duration, schedule, variability, and week versus weekend discrepancies of sleep in three distinct age groups within the school-age period. METHODS: Participants were divided by age: Cycle 1, 6 and 7 years; Cycle 2, 8 and 9 years; and Cycle 3, 10 and 11 years. For seven consecutive nights, sleep was assessed in the home environment using an actigraph. RESULTS: Compared to children of Cycle 1, those of Cycles 2 and 3 showed increasing and significant delays in sleep start time, increasingly shorter assumed and actual sleep durations, and larger night-to-night variability of sleep. Of the children in Cycles 1, 2, and 3, 96%, 87.7%, and 51.3%, respectively, were found to spend the recommended 9-11 h in bed. However, the actigraphic 'true sleep' measure revealed that only 17%, 7%, and 2.5% of these children, respectively, obtained the recommended amount of sleep. CONCLUSION: Sleep duration, schedule, and variability change significantly across the school age period. PMID- 29793185 TI - Production of biogas (methane and hydrogen) from anaerobic digestion of hemicellulosic hydrolysate generated in the oxidative pretreatment of coffee husks. AB - Ozone pretreatment of coffee husks (CH) was evaluated to generate hydrolysates for biogas production and to preserve cellulose of the solid phase for 2G ethanol production. Pretreatment variables included liquid-to-solid ratio (LSR), pH and specific applied ozone load (SAOL). Considering single-stage anaerobic digestion (AD), the highest methane production (36 NmL CH4/g CH) was achieved with the hydrolysate generated in the experiment using LSR 10 mL/g, pH 11 and SAOL 18.5 mg O3/g CH, leading to 0.064 kJ/g CH energy recovery. Due to the presence of toxic compounds in the hydrolysate, the addition of powdered activated carbon (4 g/L) to the reactor enhanced biogas production, leading to 86 NmL CH4/g CH yield and 0.58 kJ/g CH energy recovery. When two-stage AD was applied, methane production resulted in 49 NmL CH4/g CH, with additional 19 NmL H2/g CH production, resulting in a net 0.26 kJ/g CH energy recovery. PMID- 29793183 TI - Environmental radionuclides as contaminants of HPGe gamma-ray spectrometers: Monte Carlo simulations for Modane underground laboratory. AB - The main limitation in the high-sensitive HPGe gamma-ray spectrometry has been the detector background, even for detectors placed deep underground. Environmental radionuclides such as 40K and decay products in the 238U and 232Th chains have been identified as the most important radioactive contaminants of construction parts of HPGe gamma-ray spectrometers. Monte Carlo simulations have shown that the massive inner and outer lead shields have been the main contributors to the HPGe-detector background, followed by aluminum cryostat, copper cold finger, detector holder and the lead ring with FET. The Monte Carlo simulated cosmic-ray background gamma-ray spectrum has been by about three orders of magnitude lower than the experimental spectrum measured in the Modane underground laboratory (4800 m w.e.), underlying the importance of using radiopure materials for the construction of ultra-low-level HPGe gamma-ray spectrometers. PMID- 29793186 TI - Excess sludge disruption and pollutant removal from tannery effluent by upgraded activated sludge system. AB - This study proposed a maintenance metabolism based upgraded activated sludge as MANODOX system that restricts excess biosludge generation from high strength real tannery effluent. The MANODOX experimental demonstration has been done using a sequenced operational arrangement of a MBBR, anaerobic digester, and oxidation ditch connected to CAS reactor, discussed in detail manner. Experimental trends revealed a prominently lower sludge yield upto 0.271 gVSS/gCOD (72% overall sludge reduction) that corresponds to parallel run CAS (0.92 gVSS/gCOD). MANODOX implementation confirmed high quality treated effluent with prominent COD and suspended solids reduction upto 97.1% and 96% respectively. The biodegradability observation was further supported by anaerobic and aerobic batch digestion analysis. The variation of soluble component turbidity analysis reflects the enriched non-flocculating predatory microbial population appears to may have been responsible for sludge reduction. MANODOX system provided a sustainable practical alternative for under capacity activated sludge based treatment facilities for a variety of wastewater types. PMID- 29793188 TI - Prioritization of reproductive toxicants in unconventional oil and gas operations using a multi-country regulatory data-driven hazard assessment. AB - BACKGROUND: Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases. METHODS: GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple adverse effects. RESULTS: We observed substantial inconsistencies in classification among the 11 databases. By adopting the most stringent classification within and across countries, 43 chemicals were classified as known or presumed human reproductive toxicants (GHS Category 1), while 31 chemicals were classified as suspected human reproductive toxicants (GHS Category 2). The 43 reproductive toxicants were further subjected to analysis for carcinogenic and mutagenic properties. Calculated hazard scores and Cytoscape visualization yielded several high priority chemicals including potassium dichromate, cadmium, benzene and ethylene oxide. CONCLUSIONS: Our findings reveal diverging GHS classification outcomes for UOG chemicals across regulatory agencies. Adoption of the most stringent classification with application of hazard scores provides a useful approach to prioritize reproductive toxicants in UOG and other industries for exposure assessments and selection of safer alternatives. PMID- 29793187 TI - STAPP: Spatiotemporal analysis of plantar pressure measurements using statistical parametric mapping. AB - BACKGROUND: Pedobarography produces large sets of plantar pressure samples that are routinely subsampled (e.g. using regions of interest) or aggregated (e.g. center of pressure trajectories, peak pressure images) in order to simplify statistical analysis and provide intuitive clinical measures. RESEARCH QUESTION: We hypothesize that these data reductions discard gait information that can be used to differentiate between groups or conditions. METHODS: To test the hypothesis of null information loss, we created an implementation of statistical parametric mapping (SPM) for dynamic plantar pressure datasets (i.e. plantar pressure videos). Our SPM software framework brings all plantar pressure videos into anatomical and temporal correspondence, then performs statistical tests at each sampling location in space and time. Novelly, we introduce non-linear temporal registration into the framework in order to normalize for timing differences within the stance phase. We refer to our software framework as STAPP: spatiotemporal analysis of plantar pressure measurements. Using STAPP, we tested our hypothesis on plantar pressure videos from 33 healthy subjects walking at different speeds. RESULTS: As walking speed increased, STAPP was able to identify significant decreases in plantar pressure at mid-stance from the heel through the lateral forefoot. The extent of these plantar pressure decreases has not previously been observed using existing plantar pressure analysis techniques. SIGNIFICANCE: We therefore conclude that the subsampling of plantar pressure videos - a task which led to the discarding of gait information in our study - can be avoided using STAPP. PMID- 29793189 TI - Effects of exposure to anti-vaping public service announcements among current smokers and dual users of cigarettes and electronic nicotine delivery systems. AB - INTRODUCTION: Anti-vaping public service announcements (PSAs) are intended to discourage vaping or use of electronic nicotine delivery systems (ENDS). However, vaping portrayals in PSAs may have unintended effects if they increase smoking or vaping urges. This study examined benefits and unintended effects of anti-vaping PSAs with vapor portrayals on smoking and vaping-related outcomes. METHODS: Young adult smokers (N = 171) and dual users (N = 122) aged 21-30 years were randomly assigned to view: 1) anti-vaping PSAs with vapor; 2) anti-vaping PSAs without vapor; 3) physical activity PSAs; or 4) anti-smoking PSAs with smoking cues. Outcomes were changes in vaping and smoking urges before and after viewing PSAs, post-test vaping and smoking intentions in the next hour, and post-test intention to purchase ENDS and traditional cigarettes. RESULTS: Smokers only: Exposure to anti-vaping PSAs with vapor (vs. physical activity) was associated with lower intention to vape and to purchase ENDS (ps < 0.001) and lower intention to smoke and purchase cigarettes (ps < 0.05). Exposure to anti-vaping PSAs with vapor (vs. PSAs without vapor and vs. anti-smoking PSAs with smoking cues) was associated with lower intention to vape in the next hour (ps < 0.05). Exposure to anti vaping PSAs without vapor (vs. physical activity) was associated with lower change in vaping urge (p < 0.05) and intention to purchase ENDS (p < 0.001). Dual users: Exposure to anti-vaping PSAs without vapor (vs. anti-smoking PSAs) was associated with lower intention to purchase ENDS (p < 0.05). CONCLUSION: Viewing anti-vaping PSAs with vapor was not associated with unintended effects and may have benefits on reducing smoking and vaping-related outcomes. PMID- 29793190 TI - Comparative hazards of acute myocardial infarction among hospitalized patients with methamphetamine- or cocaine-use disorders: A retrospective cohort study. AB - BACKGROUND: It is assumed that recreational use of methamphetamine can trigger acute myocardial infarction (AMI) events, but estimates of longitudinal hazards of AMI among methamphetamine users are lacking. METHODS: Retrospective cohort study: Competing-risks analysis was used to estimate time-to-AMI patterns in methamphetamine versus matched appendicitis (population-proxy) and matched cocaine (drug-control) groups. Cohorts were propensity-score-matched using demographic and clinical variables. SETTING: California, 1990-2005. PARTICIPANTS: Cohorts of individuals with no prior or concurrent history of AMI hospitalized with methamphetamine- (n = 73,056), cocaine- (n = 47,726), or appendicitis related conditions (n = 330,109). MEASUREMENTS: ICD-9/ICD-10 indications of AMI (ICD-9 410.X; ICD-10 I21.X) in death records or inpatient hospital data. RESULTS: Patients in methamphetamine cohort were more likely to develop subsequent AMI in comparison to those in matched appendicitis cohort [Hazard ratio (HR): 1.41; 95% CI, 1.23-1.62, p < 0.0001], with increased risk most marked in young methamphetamine users (age 15-34 years; HR: 2.04; 95% CI, 1.63-2.57, p = 0. 0001). Risk was slightly increased vs. that in matched cocaine group (HR: 1.19; 95% CI, 1.02-1.39, p = 0. 029). Individuals in cocaine cohort were also more likely to experience AMI outcome vs. appendicitis cohort (HR: 1.25; 95% CI, 1.08 1.45, p = 0. 0023). CONCLUSION: Our longitudinal data support results of earlier epidemiological studies suggesting that persons with methamphetamine- (or cocaine ) use disorders might have increased AMI risk. However, because of potential study limitations and the unexpectedly modest magnitude of the observed increased AMI hazard, these findings must be considered preliminary and require replication. PMID- 29793191 TI - Development and validation of a prediction model for functional decline in older medical inpatients. AB - OBJECTIVE: To prevent functional decline in older inpatients, identification of high-risk patients is crucial. The aim of this study was to develop and validate a prediction model to assess the risk of functional decline in older medical inpatients. METHODS: In this retrospective cohort study, patients >=65 years admitted acutely to medical wards were included. The healthcare database of 246 acute care hospitals (n = 229,913) was used for derivation, and two acute care hospitals (n = 1767 and 5443, respectively) were used for validation. Data were collected using a national administrative claims and discharge database. Functional decline was defined as a decline of the Katz score at discharge compared with on admission. RESULTS: About 6% of patients in the derivation cohort and 9% and 2% in each validation cohort developed functional decline. A model with 7 items, age, body mass index, living in a nursing home, ambulance use, need for assistance in walking, dementia, and bedsore, was developed. On internal validation, it demonstrated a c-statistic of 0.77 (95% confidence interval (CI) = 0.767-0.771) and good fit on the calibration plot. On external validation, the c-statistics were 0.79 (95% CI = 0.77-0.81) and 0.75 (95% CI = 0.73-0.77) for each cohort, respectively. Calibration plots showed good fit in one cohort and overestimation in the other one. CONCLUSIONS: A prediction model for functional decline in older medical inpatients was derived and validated. It is expected that use of the model would lead to early identification of high-risk patients and introducing early intervention. PMID- 29793192 TI - How did older adults respond to challenges after an earthquake? Results from a qualitative study in Iran. AB - OBJECTIVES: In many areas, natural disasters are a major challenge for life and property of people. Earthquake is one of the most devastating natural disasters. This study aimed to explore how older adults responded to challenges after the earthquake in Iran. METHODS: This study was based on qualitative analysis. Data were collected through in-depth and semi-structured interviews. 29 participants including 18 older adult survivors of the earthquake-stricken areas, four lay caregivers, and three health professionals in disasters, one social worker, two relief worker and one disaster psychologist were interviewed. The interviews were recorded and transcribed. The transcribed texts were analyzed using inductive qualitative content analysis recommended by Graneheim and Lundman (2004). RESULTS: The study explored two main categories regarding older adults' responses to challenges after the earthquake: adaptive and maladaptive responses. Adaptive response has been developed by four factors including; religious coping, sharing feelings and information, coping with new activities, roles and place. Also, maladaptive response was included; the lack of motivation to search for relief supplies, undue dependency, and decrease of social activities. CONCLUSION: Service providers are recommended to identify the patterns of vulnerability and cultural sensitivities in older adults' responses to manage the negative consequences of disasters on older adults. Furthermore, older adults can make a substantial contribution in recovery programs based on the adaptive responses, such as helping in the rescue efforts and psychological support from family and community after disasters. PMID- 29793193 TI - A validation study of the 1,2-indandione reagent for operational use in the UK: Part 2 - Optimization of processing conditions. AB - This paper contains details of work carried out to identify the most effective processing conditions for the optimized 1,2-indandione/zn formulation developed for use under UK conditions. Using direct measurements of fluorescence taken from test spots of amino acids and eccrine sweat during oven processing, complemented with experiments on real fingermarks, it was established that processing temperatures above 120 degrees C in the oven were detrimental to the fluorescence of the developed mark. Alternative methods of development to oven processing were found to be effective, but less controllable. High levels of humidification were also found to be detrimental to the fluorescence of 1,2-indandione developed marks, and oven processing at 100 degrees C and 0% relative humidity is therefore recommended for further studies. It has also been shown that 1,2-indandione can develop fingermarks at temperatures as low as 20 degrees C, making it a candidate for use at crime scenes. PMID- 29793194 TI - Simultaneous determination of 18 psychoactive agents and 6 metabolites in plasma using LC-MS/MS and application to actual plasma samples from conscription candidates. AB - In Korea, an increasing number of people attempt to evade military conscription by posing as mental health patients. To verify the authenticity of mental illness, there is a need to detect wide range of psychoactive agents in biological specimens of conscription candidates. In this study, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of 18 psychoactive agents and 6 metabolites in human plasma. The method was characterized by the use of a simple, fast and cheap protein precipitation as sample preparation, a rapid run time (11min) and a low volume of plasma sample (200MUL). The analytes were monitored under the scheduled multiple reaction monitoring (sMRM) positive and negative mode using electrospray ionization (ESI). The essential validation parameters including selectivity, linearity, accuracy, precision, matrix effect and recovery were satisfactory. The limit of detection ranged from 0.0005 to 0.001MUg/mL, and limit of quantitation ranged from 0.005 to 0.025MUg/mL. The developed method was successfully applied to 323 actual plasma samples submitted by Korea central physical examination center of military manpower administration in 2016, and is expected to contribute to the rapid and accurate disposition of military service. PMID- 29793195 TI - Alcohol and drugs use among drivers injured in road accidents in Campania (Italy): A 8-years retrospective analysis. AB - A recent update of the Italian Road Traffic Law (RTL 41/2016), established severe penal sanctions when drivers, driving under the influence of alcohol (DUI) or drugs (DUID), are involved in road accident that results in death or injuries. A study was carried out to assess the trends of consumption of alcohol, illicit drugs or pharmaceutical among injured drivers suspected for DUI or DUID from 2009 to 2016 in the region of Campania (Italy). Confirmation toxicological analyses were performed on 780 blood samples and 1017 urine samples collected from 1797 injured drivers. These drivers all tested positive for alcohol or drug use through immunoassay screening applied at hospital emergency units and their biological samples transferred to the Forensic Reference Laboratory (FRL) for confirmation analysis. The GC/HS-FID methodology was used to test Blood Alcohol Concentration (BAC). Qualitative and quantitative analyses for drugs were performed using the GC/MS or LC-MS/MS methodology. The BAC >0.5g/L was confirmed in 91.5% of drivers suspected for DUI cases and in 93% of DUID respectively. In DUI cases, results show an increasing incidence of road accidents involving drivers with BAC above 1.5g/L while at concentrations above 0.8g/L alcohol and drugs are both used. Among the suspected DUID cases, the intake of alcohol in association with drugs has consistently increased over time and positive results on blood samples was confirmed for multiple drugs (20%) or cannabis and cocaine alone (18%) followed by benzodiazepines (6%) and methadone (3.5%) respectively. The majority of injured drivers suspected for DUID (1017 cases) did not authorize blood sampling, therefore only urine was analyzed showing the prevalent use of cannabis, followed by multiple drug>cocaine>benzodiazepines>opiates. Among 1797 drivers, suspected at screening for DUI or DUID, 15.4% of cases (64 blood and 213 urine samples) were not confirmed by GC/HS, GC/MS or LC-MS/MS analysis. In forensic toxicological investigations, it is mandatory to satisfy the best quality standards, which is not achievable if immunochemical screening is only performed on urine. Therefore, only confirmed positive results of alcohol or drugs on blood samples can represent conclusive evidence to demonstrate the DUI or DUID related offences. An improvement of the protocols currently applied in Italy for the assessment of DUI or DUID crimes is needed and the confirmation analysis on blood should be considered mandatory. PMID- 29793197 TI - Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study. AB - Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (SigmaAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median SigmaAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 MUg/g creatinine and 424 ms in the main cohort and 4.3 MUg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest SigmaAs quartile (>14.4 vs. <5.2 MUg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 MUg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization. PMID- 29793198 TI - Assessment of Cu sub-lethal toxicity (LC50) in the cold-water gorgonian Dentomuricea meteor under a deep-sea mining activity scenario. AB - Previous aquaria-based experiments have shown dissolution and leaching of metals, especially copper (Cu), from the simulated sediment plumes generated during mining activities resulting in a pronounced increase of Cu contamination in the surrounding seawater. Metals are bioavailable to corals with food, through ingestion (particulate phase) and through tissue-facilitated transport (passive diffusion). With corals being particularly vulnerable to metal contamination, resuspension of metal-bearing sediments during mining activities represents an important ecological threat. This study was undertaken to evaluate the impact of acute copper exposure (LC50;96 h) on the survival of the cold-water octocoral Dentomuricea aff. meteor. The experimental design was divided in two stages. In stage one, a Cu range-finding toxicity test was performed using Cu dilutions in filtered seawater with concentrations of 0 (control); 60; 150; 250; 450; 600 MUg/L. Coral mortality was investigated visually based on the percent surface area of tissue changing from natural yellow colour to black colour indicative of tissue necrosis and death. In stage two, we used the results obtained in the range-finding experiment, to define sub-lethal Cu exposure treatments and exposed D. meteor to Cu concentration of 0 (control); 50; 100; 150; 200; 250 MUg/L for 96 h. The corals physical conditions were inspected daily and seawater conditions recorded. Corals were considered dead when all of their tissue turned black. The LC50 value was calculated with regression analysis following Probits methodology. Our results indicate that Cu LC50;96 h for the octocoral D. meteor is 137 MUg/L. PMID- 29793196 TI - Seasonal cycles of secondary organic aerosol tracers in rural Guangzhou, Southern China: The importance of atmospheric oxidants. AB - Thirteen secondary organic aerosol (SOA) tracers of isoprene (SOAI), monoterpenes (SOAM), sesquiterpenes (SOAS) and aromatics (SOAA) in fine particulate matter (PM2.5) were measured at a Pearl River Delta (PRD) regional site for one year. The characteristics including their seasonal cycles and the factors influencing their formation in this region were studied. The seasonal patterns of SOAI, SOAM and SOAS tracers were characterized over three enhancement periods in summer (I), autumn (II) and winter (III), while the elevations of SOAA tracer (i.e., 2,3 dihydroxy-4-oxopentanoic acid, DHOPA) were observed in Periods II and III. We found that SOA formed from different biogenic precursors could be driven by several factors during a one-year seasonal cycle. Isoprene emission controlled SOAI formation throughout the year, while monoterpene and sesquiterpene emissions facilitated SOAM and SOAS formation in summer rather than in other seasons. The influence of atmospheric oxidants (Ox) was found to be an important factor of the formation of SOAM tracers during the enhancement periods in autumn and winter. The formation of SOAS tracer was influenced by the precursor emissions in summer, atmospheric oxidation in autumn and probably also by biomass burning in both summer and winter. In this study, we could not see the strong contribution of biomass burning to DHOPA as suggested by previous studies in this region. Instead, good correlations between observed DHOPA and Ox as well as [NO2][O3] suggest the involvement of both ozone (O3) and nitrogen dioxide (NO2) in the formation of DHOPA. The results showed that regional air pollution may not only increase the emissions of aromatic precursors but also can greatly promote the formation processes. PMID- 29793199 TI - Effects of acute and chronic exposures of fluoxetine on the Chinese fish, topmouth gudgeon Pseudorasbora parva. AB - Fluoxetine is a selective serotonin reuptake inhibitor used as an antidepressant and has been frequently detected in aquatic environments. However, its effects in fish from Asia remain relatively less studied. In this study, the topmouth gudgeon Pseudorasbora parva was exposed to 0, 50, and 200 ug/L of fluoxetine for 4 h and 42 d. The effects of fluoxetine on biometrics were compared to biochemical endpoints indicative of stress in different fish tissues (brain, liver, gills and intestine) following exposures. In fish exposed for 42 d, lipid peroxidation endpoints were enhanced 80% in the liver and gills. Acetylcholinesterase (AChE) activity was increased 40% after exposure to 50 ug/L and 55% at 200 ug/L following 4 h exposure. In contrast AChE was increased 26% (at 50 ug/L) after 42 d of exposures. Enhanced ethoxyresorufin-O-deethylase activity (EROD) was detected only in fish exposed to 50 ug/L of fluoxetine for 4 h. The activity of alpha-glucosidase (alpha-Glu) was also induced (at 200 ug/L) after 4 h of exposure. After 4 h of exposure, the activities of proteases in the intestine were generally inhibited at 200 ug/L. Both 4 h and 42 d exposures resulted in an increased hepatosomatic index (HSI) but did not affect the condition factor (CF). Our results demonstrate that fluoxetine significantly altered biochemical endpoints in P. parva after acute exposure and the morphological changes in liver size were not observed until 42 d of exposure. PMID- 29793200 TI - Influence of auxochrome group in disperse dyes bearing azo groups as chromophore center in the biotransformation and molecular docking prediction by reductase enzyme: Implications and assessment for environmental toxicity of xenobiotics. AB - Synthetic azo dyes have increasingly become a matter of great concern as a result of the genotoxic and mutagenic potential of the products derived from azo dye biotransformation. This work evaluates the manner in which reducing enzymes produced by Escherichia coli (E. coli) act on three disperse dyes bearing azo groups, namely Disperse Red 73 (DR 73), Disperse Red 78 (DR 78), and Disperse Red 167 (DR 167). UV-Vis spectrophotometry, high-performance liquid chromatography with diode array detector (HPLC-DAD), and liquid chromatography mass spectrometry (LC-MS/MS) were applied towards the identification of the main products. Seven days of incubation of the azo dyes with the tested enzymes yielded a completely bleached solution. 3-4-Aminophenyl-ethyl-amino-propanitrile was detected following the biotransformation of both DR 73 and DR 78. 4-Nitroaniline and 2 chloro-4-nitroaniline were detected upon the biotransformation of DR 73 and DR 78, respectively. The main products derived from the biotransformation of DR 167 were dimethyl 3,3'-3-acetamido-4-aminophenyl-azanedyl-dipropanoate and 2-chloro-4 nitroaniline. The results imply that DR 73 lost the CN- substituent during the biotransformation. Furthermore, theoretical calculations were also carried out aiming at evaluating the interaction and reactivity of these compounds with DNA. Taken together, the results indicate that DR 73, DR 78, and DR 167 pose health risks and serious threats to both human beings and the environment at large as their biotransformation produces harmful compounds such as amines, which have been widely condemned by the International Agency for Research on Cancer. PMID- 29793201 TI - Positive effects of an oil adjuvant on efficacy, dissipation and safety of pyrimethanil and boscalid on greenhouse strawberry. AB - Methylated vegetable oil adjuvants can enhance initial deposition and decrease the required dosages of pesticides sprayed on plants, so an oil adjuvant mixed with fungicides were used to prevent and control gray mold in greenhouse strawberry. As the persistence and dietary exposure risks from fungicides on strawberries after using adjuvants have not been assessed, the efficacy, dissipation and safety of pyrimethanil and boscalid in the presence and absence of a methylated vegetable oil adjuvant were evaluated. To better describe the actual use of fungicides in greenhouse strawberry, twice repeated application of fungicides were conducted follower by an optimized QuEChERS pre-treatment method. When applied at 60% of their recommended dosages with the adjuvant, the efficacy of pyrimethanil and boscalid for gray mold was similar to that shown by the treatment of 100% fungicides in absence of the adjuvant based on Duncan's Multiple-Range test, and their average residues increased to 89.0% and 89.3%, respectively. The adjuvant enhanced the accumulation effect of pyrimethanil residue by 31.7% after repeated applications, and the half-lives were similar (5.2 and 4.2 d). The adjuvant had comparable accumulation effects (1.75 and 1.83) and similar half-lives (5.4 and 5.5 d) for boscalid. In absence of adjuvant, the risk quotients (RQs) of pyrimethanil (0.41 and 0.33) and boscalid (0.49 and 0.63) after twice applications at pre-harvest interval were lower than 1. Adding the methylated vegetable oil adjuvant to fungicides would result in unprolonging half life and acceptably low dietary exposure risk on strawberries, but lower dosage of fungicides were used. PMID- 29793202 TI - iTRAQ-based quantitative proteomic analysis of the earthworm Eisenia fetida response to Escherichia coli O157:H7. AB - Soil environment contaminated by Escherichia coli O157:H7 which come from the waste of infected animals. Earthworms can live in the pathogens-polluted soil by their innate immunity. How the proteins of earthworms E. fetida will response to E. coli O157:H7-contaminated-soil still unclear? To identify the defense proteins under E. coli O157:H7 stress, we performed a proteomic analysis of earthworm under E. coli O157:H7 exposure through an iTRAQ technology. In total, we found 283 non-redundant proteins, including fibrinolytic protease 1, lombricine kinase, lysozyme, gelsolin, coelomic cytolytic factor-1, antimicrobial peptide lumbricin l, lysenin, and et al. The proteins participate in metabolic processes, transcription, defense response to bacterium, translation, response to stress, and transport. The study will contribute to understand why earthworm can live in the pathogens-polluted environment. PMID- 29793203 TI - Chemical speciation and risk assessment of cadmium in soils around a typical coal mining area of China. AB - The distribution characteristics of Cadmium (Cd) fractions in soils around a coal mining area of Huaibei coalfield were investigated, with the aim to assess its ecological risk. The total Cd concentrations in soils ranged from 0.05 to 0.87 mg/kg. The high percentage of phyto-available Cd (58%) when redox or base-acid equilibria changed. Soil pH was found to be a crucial factor affecting soil Cd fraction, and carbonate-bound Cd can be significantly affected by both organic matter and pH of soils. The static ecological evaluation models, including potential ecological risk index (PERI), geo-accumulation index (Igeo) and risk assessment code (RAC), revealed a moderate soil Cd contamination and prensented high Cd exposure risk in studied soils. However, the dynamic evaluation of Cd risk, determined using a delayed geochemical hazard (DGH), suggested that our studied soils can be classified as median-risk with a mean probability of 24.79% for Cd DGH. These results provide a better assessment for the risk development of Cd contamination in coal mining areas. PMID- 29793204 TI - Influence of isolated bacterial strains on the in situ biodegradation of endosulfan and the reduction of endosulfan- contaminated soil toxicity. AB - The recently discovered endosulfan-degrading bacterial strains Pusillimonas sp. JW2 and Bordetella petrii NS were isolated from endosulfan-polluted water and soil environments. The optimal conditions for the growth and biodegradation activity of the strains JW2 and NS were studied in detail. In addition, the ability of the strains JW2 and NS to biodegrade endosulfan in soils during in situ bioremediation experiments was investigated. At a concentration of 2 mg of endosulfan per kilogram of soil, both JW2 and NS had positive effects on the degradation of endosulfan; JW2 degraded 100% and 91.5% of alpha- and beta endosulfan, respectively, and NS degraded 95.1% and 90.3% of alpha- and beta endosulfan, respectively. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) of soil samples showed the successful colonization of JW2 and NS, and the toxicity of the soil decreased, as determined by single-cell gel electrophoresis (SCGE) assays of Eiseniafetida and micronucleus (MN) assays of Viciafaba root tip cells. Furthermore, the metabolic products of the bacterially degraded endosulfan from the in situ experiments were identified as endosulfan ether and lactone. This study provided potentially foundational backgrounds information for the remediation of endosulfan-contaminated soil. PMID- 29793205 TI - Comprehensive assessment of three typical antibiotics on cyanobacteria (Microcystis aeruginosa): The impact and recovery capability. AB - This innovative study provided a comprehensive evaluation of the effects of three typical antibiotics exposures (cefradine, norfloxacin and amoxicillin) on Microcystis aeruginosa in two periods (exposure and post-exposure) at a new perspective. The results indicated that the irreversible growth inhibition of M. aeruginosa attributed to the norfloxacin in the exposure and the re-exposure stages. In contrast, although the algal cell size recovered to the control level after the exposure of 20 mg/L of cefradine, the significant stimulation on glutathione (GSH) still persisted even if the contaminants were removed. On the other hand, amoxicillin inhibited the activities of superoxide dismutase (SOD), GSH contents and the algal cell size in the exposure period while malonaldehyde (MDA) contents increased significantly in two periods. PMID- 29793206 TI - Effects on the hepatic transcriptome of chicken embryos in ovo exposed to phenobarbital. AB - This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 MUg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. In the PB treatment group, a 7% attenuation in tarsus length was found in females. While no adverse phenotypic effect on the liver somatic index (LSI) was observed, PB caused significant changes in the expressions of 52 genes in males and 516 genes in females (False Discovery Rate < 0.2, p value < 0.05, and absolute fold change > 2). PB exposure modulated the genes primarily enriched in the biological pathways of the cancer, cardiac development, immune response, lipid metabolism, and skeletal development in both genders, and altered expressions of genes related to the cellular process and neural development in females. However, mRNA expressions of chicken xenobiotic receptor (CXR)-mediated CYP genes were not induced in the PB treatment groups, regardless of males and females. On the contrary, PB exposure repressed the mRNA expressions of CYP2AC2 in males and CYP2R1, CYP3A37, and CYP8B1 in females. Although transcription factors (TFs) including SREBF1 and COUP-TFII were predicted to be commonly activated in both genders, some TFs were activated in a gender-dependent manner, such as PPARa in males and BRCA1 and IRF9 in females. Taken together, our results provided an insight into the mode of action of PB on the chicken embryos. PMID- 29793207 TI - Infectivity reduction efficacy of UV irradiation and peracetic acid-UV combined treatment on MS2 bacteriophage and murine norovirus in secondary wastewater effluent. AB - Peracetic acid (PAA) is a strong oxidant/bactericide that has been applied in various industries (e.g., food processing, pharmaceuticals, medical device sterilization, etc.) as a disinfectant. There is increasing interest in using PAA for wastewater disinfection because it does not form halogenated byproducts, and no post-treatment quenching is required. Previous studies have demonstrated good efficiency in controlling bacteria in wastewater, but limited information is available for viruses, especially those hosted by mammals (e.g., norovirus). Therefore, a study on the infectivity reduction of murine norovirus (MNV) was undertaken to evaluate the disinfection efficacy of PAA or UV alone and in combination with UV irradiation in undisinfected secondary effluent from a municipal wastewater reclamation facility (MWW) and phosphate buffer solution (PBS) at pH 7. Experiments employing MS2 bacteriophage were also performed in parallel for comparison purposes. MS2 infectivity reduction was found to be lower than MNV infectivity reduction for each condition studied - PAA, PAA + UV, and UV disinfection. These data suggest that MS2 may not be an appropriate surrogate to accurately predict the reduction of MNV infectivity. UV irradiation, in a dose range of 5-250 mJ/cm2, provided linear log inactivation (-log (N/N0)) with a regression slope (cm2mJ-1) of 0.031-0.034 and 0.165-0.202 for MS2 and MNV, respectively. UV irradiation provided similar inactivation for MS2 and MNV in both suspensions (PBS or MWW). Low infectivity reduction of MS2 was observed when PAA was used alone at a practical dose of 1.5 mg/L and below. A greater reduction of both MNV and MS2 was observed in PAA disinfection experiments using PBS as the microbial suspension medium, than in secondary effluent. Similar results were observed in PAA + UV experiments, in which greater synergistic effects were found in PBS than in MWW. Results of OH radical formation experiments suggest the presence of radical scavengers in MWW, which resulted in less opportunity for MNV and MS2 to encounter OHradicals. This study also demonstrated that the type of water can have a substantial impact on wastewater disinfection when employing PAA or PAA + UV treatment due to the matrix effect and the presence of radical scavengers, respectively. The results from this study could be employed to aid in the conceptual design of PAA and UV disinfection facilities, especially when norovirus is the organism of concern. PMID- 29793209 TI - Effect of thermal pretreatment on chemical composition, physical structure and biogas production kinetics of wheat straw. AB - Hard lignocellulosic structure of wheat straw is the main hindrance in its anaerobic digestion. Thus, a laboratory scale batch experiment was conducted to study the effect of thermal pretreatment on anaerobic digestion of wheat straw. For this purpose, different thermal pretreatment temperatures of 120, 140, 160 and 180 degrees C were studied and the results were compared with raw wheat straw. Significant differences in biogas production were observed at temperature higher than 160 degrees C. Highest biogas yield of 615 Nml/gVS and volatile solids reduction of 69% was observed from wheat straw pretreated at 180 degrees C. Wheat straw pretreated at 180 degrees C showed 53% higher biogas yield as compared to untreated. Further, FTIR analysis revealed change in chemical bonds of lignocellulosic structure of wheat straw. Modified Gompertz model was best fitted on biogas production data and predicted shorter lag phase time and higher biogas production as the pretreatment temperature increased. Overall, change in lignocellulosic structure and increase in cellulose content were the main reason in enhancing biogas production. PMID- 29793208 TI - Enhanced phosphate removal from wastewater by using in situ generated fresh trivalent Fe composition through the interaction of Fe(II) on CaCO3. AB - Excessive existences of nutrients such as phosphate in the aqueous environment remain as a heavy concern although many researches have been reported for dealing with their removal. Based on the understanding toward the interactions of Fe compounds with phosphate and carbonate from many available researches, we designed a very simple and efficient approach for phosphate removal by using in situ generated fresh trivalent Fe composition through the interaction of Fe(II) as FeSO4 on CaCO3. Addition and agitation of Fe(II) and CaCO3 simultaneously to phosphate solution allowed an amorphous Fe(III)-P or Ca-Fe(III)-P precipitation, with a phosphate removal rate close to 100%, to reduce the residual phosphorus concentration less than 0.03 mg/L from 100 mg/L, reaching the discharge limit, even with the addition amounts of CaCO3 as low as a stoichiometric ratio of CaCO3/PO43- at 0.9 and ratio of Fe(II)/PO43- at 1.5, and the percent of P2O5 in the precipitate was as high as 19.4% enough as phosphate source for fertilizer production. Different from the alkaline process with enough OH- group, the slow hydrolysis of CaCO3 resulting in low concentration of OH- group for the formation of Fe(OH)2, which was oxidized soon by air into trivalent Fe, achieved a continuous generation of fresh ferric composition for phosphate precipitation and could avoid its rapid formation and subsequent transformation into stable FeOOH of large particle size to lose the activity. These results based on the synergistic effect of using CaCO3 and Fe(II) together may have applications in the treatment of eutrophic wastewater through a process with many advantages of easy operation and low-cost besides the high removal efficiency with phosphate percentage inside the precipitate high enough to serve for fertilizer production. PMID- 29793210 TI - Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system. AB - The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3 carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (Ki = 23.1 nM, partial agonist) and CB2R (Ki = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC50 = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC50 = 2.5 MUMU). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub micromolar IC50 values (0.28-0.62 MUMU). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds. PMID- 29793211 TI - Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents. AB - The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover novel series of 25 compounds for the development of new antileishmanial agents. A series of triazolyl 2-methyl-4 phenylquinoline-3-carboxylate derivatives has been synthesized via click chemistry inspired molecular hybridization approach and evaluated against Leishmania donovani. Most of the screened derivatives exhibited significant in vitro anti-leishmanial activity against promastigote (IC50 ranging from 2.43 to 45.75 MUM) and intracellular amastigotes (IC50 ranging from 7.06 to 34.9 MUM) than the control, miltefosine (IC50 = 8.4 MUM), with less cytotoxicity in comparison to the standard drugs. Overall results revealed that prototype signify a new structural lead for antileishmanial chemotherapy. PMID- 29793212 TI - Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas, incidental or non-incidental? AB - The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8 Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision. PMID- 29793213 TI - End-Stage Renal Disease Models in the Americas: Optimizing Resources to Achieve Better Health Outcomes. AB - End-stage renal disease, the last and most severe stage of chronic kidney disease, represents a major and rising concern for countries in Latin America, driven in large part by aging populations and the near-epidemic rises in diabetes, obesity, and hypertension. This places a great clinical, economic, and social burden on the region's health systems. During the ISPOR 6th Latin America Conference held in Sao Paulo, Brazil, in September 2017, an educational forum debated on value-based decision making in the treatment of end-stage renal disease in Latin America. We summarize the current state and how to build strategies and implement actions to move to a more patient-centered, outcomes based approach for renal care in the region, taken from the discussions in the conference and also from a literature review. Models of renal care used in Ontario (Canada), Colombia, and a Chilean hospital stress the importance of empowering and supporting patients and their families, allowing for a better coordination between primary care providers and specialists, providing financial incentives to health units, and establishing an entity that holds insurers and providers accountable for health outcomes and costs of treatment. The study uses the framework of value-based health care for the evaluation of different dialysis options-peritoneal dialysis, hemodialysis, home dialysis, and so forth-and calls for the countries to adopt an integrated care model. We emphasize that countries in Latin America need to recognize the chronic kidney disease challenge and develop health systems and efficient renal care models to be able to reduce the burden of the disease. PMID- 29793214 TI - Balanced design for the feasible super rocket fuels: A first-principle study on gauche CHN7 and CHN3. AB - On the basis of the framework of cubic gauche nitrogen (cg-N), six one-eighth methanetriyl groups (>CH-) substitutes and fifteen one-fourth >CH- substitutes were optimized using the first-principle calculations based on density functional theory (DFT). Both one-eighth and one-fourth substitutes still keep the gauche structures with the simple formula CHN7 and CHN3, respectively. The most thermodynamic stable gauche CHN7 and CHN3 are P21 qtg-C2H2N14 I and P21 qtg C4H4N12 III, respectively. No probability density of C-C single bonds and high probability densities of C-N-C structures were found in the two substitutes. Although gauche CHN7 and CHN3 lose energy density in contrast to cg-N, they win kinetic stability and combustion temperature (Tc). Thus, they are more feasible than cg-N, and more effective than the traditional rocket fuels. PMID- 29793215 TI - In silico insight into voltage-gated sodium channel 1.7 inhibition for anti-pain drug discovery. AB - Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors. Four accurate docking methods were employed to analyze the ligand-protein interactions in our molecular simulation study. Combining pharmacophore model with docking results, an interaction model was obtained with four features that were consistent with one another, which was more powerful in illuminating the binding site. The research elucidated a valuable relationship between structure and activity, at the same time it proposed an accurate binding model that was instructive in the development of novel and potent Nav1.7 inhibitors in the future. PMID- 29793216 TI - On the valuation of genetic tests. PMID- 29793217 TI - Personalized medicine in psychiatry. AB - Dr David Gurwitz has been a Director of The National Laboratory for the Genetics of Israeli Populations at the Sackler Faculty of Medicine, Tel-Aviv University, since its establishment in 1995. His research and teaching interests are focused on pharmacogenomics and its implications for personalized medicine, mainly in the context of neurology and psychiatry. PMID- 29793218 TI - A coalition to drive personalized medicine forward. AB - The widespread adoption of personalized medicine will require the harmonization of many components: advances in technology; changes in healthcare infrastructure and medical practice convention; improvements in the efficiency and quality of healthcare delivery; diagnostic and therapeutics business models for genetically defined markets; attempts by government and private payers to justify a new genre of tests and drugs; a different approach to regulatory oversight; and, of course, the ethical and legal issues that go along with the extensive use of genetic information in medical records. Personalized medicine is, in fact, a systems level challenge, in which no single component or stakeholder can hope to push through a coherent and encompassing policy for adoption on its own. The need for a nationwide, multi-industry policy consensus for the next generation of medicine has led to the creation of the Personalized Medicine Coalition - an independent, non-profit organization of over 20 leading pharmaceutical, diagnostic, biotechnology and information technology companies, as well as major academic institutions and governmental agencies. The Coalition provides a structure for achieving consensus positions on crucial public policy issues and serves as a forum for debate and education in personalized medicine. PMID- 29793219 TI - Millennium Pharmaceuticals, Inc. AB - Millennium Pharmaceuticals, Inc. is committed to making a difference in people's lives by developing breakthrough therapies for important diseases based on pre eminent science and drug development. The company's discovery process is built upon its deep understanding of genomics and biology by a research and development approach centered on a fundamental understanding of the basic cellular and genetic mechanisms of diseases, and by focusing on the development of personalized medicine. Over the past decade, Millennium has evolved into a fully integrated biotechnology company, with state-of-the-art discovery, development and commercial capabilities. But the company remains very much rooted in its gene based, biology heritage as the practice of medicine evolves toward delivering the right drug to the right patient at the right time - also known as personalized medicine. PMID- 29793220 TI - Genomas, Inc. AB - Genomas, Inc. is developing novel diagnostic products to personalize disease prevention and health enhancement. The company's proprietary PhysioGenomicsTM technology allows it to rapidly and precisely produce 'PhysioTypesTM'. PhysioTypes are predictors of response to diet, exercise, and drugs (not diagnostics for disease), and are utilized to direct preventive strategies. A PhysioType is made from the combination of all genetic, physiological or clinical markers that Genomas has discovered to be significant determinants of individual response. PhysioTypes are revolutionary healthcare products that empower physicians with the unprecedented capability to prescribe personalized and highly effective preventive treatments, incorporating diet, exercise and drug regimens for each patient. Genomas conducts clinical research with major clinical institutions to discover these PhysioTypes with plans to commercialize them to practicing physicians and hospitals. PMID- 29793222 TI - The impact of EGFR mutations on gefitinib sensitivity in non-small cell lung cancer. AB - Gefitinib (ZD1839, Iressa(r); AstraZeneca) has produced objective tumor responses and symptom improvement in some patients with non-small cell lung cancer. In clinical trials, 12-18.4% of patients had a rapid and often dramatic clinical response, and a subset analysis of the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1 and -2 trials demonstrated that female gender and adenocarcinoma were associated with a higher response to gefitinib. However, analysis from clinical trials have not found a relationship between epidermal growth factor receptor (EGFR) expression and response in patients receiving gefitinib. Recently, three studies have identified mutations affecting the EGFR in lung cancer from patients who respond to gefitinib. EGFR gene mutations were common in lung cancer from 'never smokers' and were associated with sensitivity of tumors to gefitinib. Furthermore, it has been reported that the phosphatidylinositol 3 kinase/Akt signaling pathway plays a critical role in the antitumor effects of gefitinib. Although EGFR mutations do not fully explain the clinical benefit, the data regarding EGFR mutations may help to define the patient population that will most likely benefit from EGFR tyrosine-kinase-targeted therapies. PMID- 29793223 TI - Quo vadis personalized medicine? PMID- 29793224 TI - Conference on Implications for Genomics and Public Health. PMID- 29793225 TI - Personalized therapy: an interdisciplinary challenge. AB - Genomics must be combined with proteomics and metabolomics to rationalize a therapeutic strategy that considers gene expression, protein expression and metabolic profiles in the target organ to gain insight into other pathways implicated in the same or contributory tissues. Multidisciplinary strategies such as this provide an interactive process by which findings are translated into novel therapies. PMID- 29793226 TI - Mannose-binding lectin: laying the stepping stones from clinical research to personalized medicine. AB - As a key component of the complement system, mannose-binding lectin (MBL) is one of the linchpins of innate immunity. It is, therefore, not surprising that MBL2 genetic variants affecting the quantity and activity of the MBL protein in serum have been associated with increased susceptibility to infection and autoimmune diseases, and with poorer prognostic outcomes. This enhanced risk is particularly the case for children and immunosuppressed patients, especially when immunity is further compromised by coexistent primary or secondary immune deficiencies. In several disease areas, such as sepsis, cystic fibrosis, and recurrent childhood infections, the association between low MBL-producing allelic variants and disease risk and/or severity is particularly strong. It is here that the use of MBL testing and replacement therapy has reached the threshold of personalized medicine. The role of MBL in health and disease, advances in MBL testing methodologies and key areas for possible applications of MBL replacement therapy are reviewed. PMID- 29793227 TI - Pharmacogenetics and pharmacogenomics of immunosuppressive agents: perspective for individualized therapy. AB - Immunosuppressive therapy has markedly improved over the past years with the advent of highly potent and rationally targeted immunosuppressive agents. Since these drugs are characterized by a narrow therapeutic index, major efforts have been carried out to define therapeutic windows based on the blood levels of each immunosuppressant, and relating those concentrations to clinical events. Although pharmacokinetic-based approaches are currently used as useful tools to guide drug dosing, they present several limitations. Pharmacogenomics - a science that studies the inherited basis of differences between individual responses to drugs in order to identify the best dose and therapy for each patient - might represent a complementary support. Preliminary studies that have focused on polymorphisms of genes encoding enzymes involved in drug metabolism, drug distribution, and pharmacological target, have shown promising results. Indeed, pharmacogenomics holds promise for improvement in the ability to individualize pharmacological therapy based on the patient's genetic profile. PMID- 29793228 TI - Genetic thrombophilia has pleiotropic effects in pregnancy. AB - Genetic thrombophilia has been established as a risk factor for pregnancy associated disorders, such as thrombosis, early and late miscarriage, and pre eclampsia. Associations between the factor V (F5) Leiden G1691A and the prothrombin/factor II (F2) G20210A SNPs and pre-eclampsia have been evaluated in over 50 association studies. A pooled analysis of 23 and 11 studies demonstrates that carriage of the F5 Leiden G1691A (p < 0.001; odds ratio [OR] 2.0; 95% confidence interval [CI] 1.6-2.5) and the F2 G20210A (p < 0.001; OR 1.8; 95% CI 1.1-2.9) SNPs is significantly associated with pre-eclampsia. Besides pre eclampsia, genotyping for the F5 Leiden G1691A and the F2 G20210A SNPs is also useful for individual risk assessment regarding pregnancy-associated thrombosis. Carriers of the F5 Leiden G1691A SNP will develop this condition in 6.4% of heterozygotes and in 8.9-16.7% of homozygotes. A total of 6.2% of women with the F2 G20210A SNP and 17.8% of women with simultaneous carriage of the F5 Leiden G1691A and F2 G20210A SNPs will develop pregnancy-associated thrombosis. Both the F5 Leiden G1691A and F2 G20210A SNPs are also risk factors of early recurrent, late recurrent and late spontaneous miscarriage based on a published meta analysis of 31 studies. These women may benefit from prophylactic heparinization. Six case-control and cohort studies of 687 women with genetic thrombophilia document live birth rates of 82% (181/221) using low-molecular-weight heparin or fractionated heparin compared with 20% (95/466) without therapy (p < 0.001, OR 17.7; 95% CI 12.2-25.5). Based on the data in the literature, including association studies and meta-analyses of these association studies, it can be concluded that genetic thrombophilia due to carriage of the F5 Leiden G1691A and F2 G20210A SNPs is a significant and clinically relevant risk factor for pre eclampsia, pregnancy-associated thrombosis, and early and late miscarriages. PMID- 29793229 TI - The CYP2C9 polymorphism: from enzyme kinetics to clinical dose recommendations. AB - CYP2C9 is the major human enzyme of the cytochrome P450 2C subfamily and metabolizes approximately 10% of all therapeutically relevant drugs. Two inherited SNPs termed CYP2C9*2 (Arg144Cys) and *3 (Ile359Leu) are known to affect catalytic function. Numerous rare or functionally silent polymorphisms have been identified. About 35% of the Caucasian population carries at least one *2 or *3 allele. CYP2C9 metabolizes several oral hypoglycemics, oral anticoagulants, non steroidal anti-inflammatory drugs and other drugs, including phenytoin, losartan, fluvastatin, and torsemide. In vitro studies with several drugs indicate that the Cys144 (.2) and Leu359 (.3) variants confer only about 70 and 10% of the intrinsic clearance of the wild-type protein (.1), respectively. The clinical pharmacokinetic implications of these polymorphisms vary depending on the enzymes contribution to total oral clearance. Several studies demonstrated that the CYP2C9 polymorphisms are medically important for non-steroidal anti-inflammatory drugs, for oral hypoglycemics, vitamin K antagonistic oral anticoagulants, and phenytoin. In particular, CYP2C9 polymorphisms should be routinely considered in therapy with oral anticoagulants where severe adverse events at initiation of therapy might be reduced by genotyping. CYP2C9 polymorphisms were also clinically associated with side effects of phenytoin, with gastric bleeding during therapy with non-steroidals and with hypoglycemia under oral hypoglycemic drugs. Data appear mature enough for the routine consideration of CYP2C9 genotypes in therapy with acenocoumarol, phenytoin, warfarin, and some other drugs. Nevertheless, it is advisable before the routine clinical use of these genotype data to rigorously test the benefits of genotype-based therapeutic recommendations by randomized controlled clinical trials. PMID- 29793230 TI - Pharmacogenomics of MDR and MRP subfamilies. AB - Drug-metabolizing enzymes, drug transporters and drug targets play significant roles as determinants of drug efficacy and toxicity. Their genetic polymorphisms often affect the expression and function of their products and are expected to become surrogate markers to predict the response to drugs in individual patients. With the sequencing of the human genome, it has been estimated that approximately 500-1200 genes code for drug transporters and, recently, there have been significant and rapid advances in the research on the relationships between genetic polymorphisms of drug transporters and interindividual variation of drug disposition. At present, the clinical studies of multi-drug resistance protein 1 (MDR1, P-glycoprotein, ABCB1), which belongs to the ATP-binding cassette (ABC) superfamily, are the most comprehensive among the ABC transporters, but clinical investigations on other drug transporters are currently being performed around the world. MDR1 can be said to be the most important drug transporter, since clinical reports have suggested that it regulates the disposition of various types of clinically important drugs, but in vitro investigations or animal experiments have strongly suggested that the members of the multi-drug resistance associated protein (MRP) subfamily can also become key molecules for pharmacotherapy. In addition to those, breast cancer resistance protein (BCRP, ABCG2), another ABC transporter, is well known as a key molecule of multi-drug resistance to several anticancer agents. However, this review focuses on the latest information on the pharmacogenetics of the MDR and MRP subfamilies, and its impact on pharmacotherapy is discussed. PMID- 29793232 TI - Role of Pharmacogenetics in Rational Development and Personalization of Drug Treatments. PMID- 29793233 TI - Personalized cancer therapy. AB - Karol Sikora is the Scientific Director of Medical Solutions Plc and Special Advisor to HCA International in the creation of the London Cancer Group - the largest UK cancer network outside the NHS in HCA's six major London private hospitals. This includes the construction of a major new international cancer center for care, teaching and research in London at the Harley St clinic. He is Professor of Cancer Medicine and honorary Consultant Oncologist at Imperial College School of Medicine, Hammersmith Hospital, London. PMID- 29793234 TI - Pharmacogenetics and individualized medicine - bridging the gap between pharmacogenetic research and the patient. AB - A considerable component of the variability seen in drug response or drug disposition has been explained by pharmacogenetic factors. Thus, diagnosing inherited variability in molecules involved in drug response may help to optimize drug therapy and provide more individualized treatment. However, despite the availability of a large amount of pharmacogenetic research data, there are still only a few examples of genotyping being incorporated into clinical drug therapy. In order to bridge the gap between pharmacogenetic research and clinical application, the unequivocal proof of the benefit of pharmacogenetic diagnostics in a certain drug therapy is warranted. But this is not all; there is a clear need for research results to be translated into clinically adoptable guidelines or, when this is not possible, more appropriately designed studies should be conducted with the aim of applying the data in the clinic. Furthermore, more education on pharmacogenetics and the genetic mechanisms underlying interindividual variability in disease susceptibility, treatment course and treatment response should be provided. As a third point, an infrastructure for genetic testing has to be established and this should not only include valid methods for genetic analyses, but especially the logistics of sample shipping, clear indications and instructions for blood sampling from patients, and valid interpretation and communication of the results. Thus, in order to routinely apply pharmacogenetic testing in drug therapy, several concrete steps have to be undertaken, in addition to the optimization of research studies. PMID- 29793235 TI - IntegraGen SA. AB - IntegraGen SA is at the stage of commercializing a series of innovative IntegraTestsTM to position itself as a leader within the rapidly growing market of predictive medicine. By applying its proprietary gene-mapping technology GenomeHIPTM (Genome Hybrid Identity Profiling) in premier patient collections, IntegraGen has rapidly discovered novel genes and genetic markers associated with a variety of complex, multifactorial diseases to use in its IntegraTests - a new class of personalized medicine diagnostics. IntegraTests provide prediction, prevention, detailed diagnosis and tailored treatment of complex diseases. Depending on the disease and the applied set of genetic markers, these tests can calculate the personal risk for acquiring the disease, define the various subforms of complex diseases, predict susceptibility to severe comorbidities, and help to define a personalized health management program. Focusing on metabolic syndrome and neuropsychiatric disorders, IntegraGen will launch its first tests in Europe in 2005. PMID- 29793236 TI - Pharmacogenetics of oral anticoagulants. AB - Understanding the basis for the observed wide interindividual variation in the dose requirement for the oral anticoagulants should facilitate the safer use of these widely prescribed drugs. Factors that include patient age, body weight and concomitant medications are well known to affect dose requirement and in a large number of recent pharmacogenetic studies, it has been demonstrated that the common variant CYP2C9 alleles are also good predictors of dose requirement, although they fail to account for all the observed interindividual variability. Since pharmacokinetic factors seem to be major contributors to the variability, the possibility that additional CYP2C9 polymorphisms or other polymorphisms affecting anticoagulant disposition could also predict dose is discussed. In addition, the relevance with regard to dose requirement of polymorphism in the recently discovered vitamin K epoxide reductase gene, which encodes the target gene for oral anticoagulants, is considered. PMID- 29793237 TI - Personalized neurology. AB - Personalized medicine simply means the prescription of specific therapeutics best suited for an individual based on pharmacogenetic and pharmacogenomic information. It involves integration of molecular diagnostics with therapeutics. Selection of a suitable medicine from various approaches available based on optimal efficacy and safety in an individual patient will be preferable to trial and-error approaches. A personalized approach will improve the management of neurological disorders, such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, neuropathic pain, and migraine. Gene therapy and RNA interference will facilitate the development of personalized treatment for neurological disorders. It is anticipated that several components of this system will be in place by the year 2010 and it will be a part of neurological practice by the year 2015. However, not all neurological disorders would require a personalized approach. PMID- 29793238 TI - personalized medicine and pharmacogenomics: ethical and social challenges. AB - Recent developments in human genetic variation research have fueled predictions of an imminent era of personalized medicine. Defined as a shift toward greater integrated and heuristic innovation in healthcare, personalized medicine seeks to create differentiated strategies for the prevention of disease defined at the molecular level [1] . Recent developments in gene sequencing technologies have focused efforts toward improving efficacy and efficiency in the drug development process. Emerging from the discipline of pharmacogenetics, pharmacogenomics - the study of gene-to-gene interactions through the use of high-throughput technologies - has gained attention as the field most able to deliver on the promises of genomic medicine [2] . The distinction between pharmacogenetics and pharmacogenomics is not clear; while some have argued that differences of scale and focus distinguish the fields, this article uses the term, 'pharmacogenomics', to mean the broad scope of research on inherited variation in drug response. Through differential diagnosis, drug response is being linked to molecular subgroups that may allow for the development of 'tailored' medications [3] . However, several challenges confront these potential benefits. Critical to the success of pharmacogenomics and personalized drug therapies are the creation of large databases containing human genotypic and phenotypic information, the adoption of pharmacogenomic testing as a standard of medical care, and greater regulatory guidance on balancing commercial and public health priorities. In anticipation of these healthcare trajectories, serious engagement with the ethical and social implications of pharmacogenomics is needed. This article reviews several of these issues and highlights concerns that must be addressed in anticipation of personalized drug development. PMID- 29793239 TI - Personalized medicine: how much can we afford? A bioethics perspective. AB - This article examines some major challenges to the clinical implementation of personalized medicine from a bioethics point of view. Challenges arise from the need to choose between competing scenarios in the allocation of healthcare resources. If a choice between competing scenarios must be made, the key question is what sort of medicine a society wants to have and how much its citizens are willing to pay for it. Cost-effectiveness is crucial, but not the only criterium. Pharmacogenomics-based personalized medicine is also challenged by competing concepts of 'good' medicine. However, a real dilemma for health policy arises when a trade-off between implementing public health practices and personalized medicine must be made. This paper tries to show that from a bioethics perspective these concepts are not mutually exclusive. In future, a scenario that seeks to integrate both concepts in a complementary fashion may maximize the benefit for both individuals and the community. PMID- 29793240 TI - The journey to personalized medicine. PMID- 29793241 TI - Marshfield Clinic Personalized Medicine Research Project (PMRP): design, methods and recruitment for a large population-based biobank. AB - OBJECTIVES: The objective of this paper is to summarize the planning for Phase I of the Marshfield Clinic Personalized Medicine Research Project (PMRP) and to describe the recruitment efforts in the first 2 years. METHODS: The purpose of Phase I of the PMRP was to develop a large population-based biobank with DNA, plasma and serum samples to facilitate genomics research. Planning and consultation was facilitated with three external boards: the Ethics and Security Advisory Board; the Scientific Advisory Board; and the Community Advisory Group. Commencing in September 2002, residents aged 18 and above who resided in 1 of 19 zip codes surrounding Marshfield, WI, USA, were invited to participate. After providing written informed consent, participants completed brief questionnaires that included questions about demographics, some environmental exposures, family history of disease, and adverse drug reactions, as well as family members living in the study area. Participants provided 50 ml of blood from which DNA was extracted and plasma and serum samples were stored. The informed consent document allowed access to electronic medical records and included language about non disclosure of personal research results. A tick-off box was also included so that participants could either allow or decline subsequent recontact for future research studies. RESULTS: A total of 17,463 subjects were enrolled during the first 23 months of recruitment (44.3% of the residents who the Research Project Assistants were able to contact). The participants ranged in age from 18 to 98.5 years (mean = 48.9, median = 48); 57.2% (n = 9986) were female. Self-reported race in the study cohort was similar to the year 2000 census for Wood County, WI, USA, with the majority (98%) reporting themselves to be White Caucasian. The majority of subjects (n = 13,391, 76.7%) indicated that they had German ancestry. Only 142 participants (< 1%) opted out on the consent form for contact for future studies. The majority of the cohort reported that their current area of residence was a suburb, city or village (n = 10630, 60.87%); the remainder reported residence in a rural home or hobby farm (n = 5365, 30.72%), or a working farm or ranch (n = 1451, 8.31%). More than half the cohort (n = 9409, 53.88%) had lived on a working farm at some point in their life. CONCLUSION: The PMRP database will allow research in three areas: genetic epidemiology, pharmacogenetics, and population genetics. The size and the stability of the population as well as the relative ethnic homogeneity will help facilitate longitudinal studies with valid research results that are not biased by population stratification. PMID- 29793242 TI - Erratum. PMID- 29793244 TI - News & Views in ... Personalized Medicine. PMID- 29793243 TI - Interview: Interview with David Mangelsdorf for Personalized Medicine. AB - David Mangelsdorf is Professor and Chair of Pharmacology at the University of Texas Southwestern Medical Center in Dallas (TX, USA) where he holds the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science and the Distinguished Chair in Pharmacology. He received his BSc in biology and chemistry from Northern Arizona University (AZ, USA) in 1981 and his PhD in biochemistry from the University of Arizona (AZ, USA) in 1987. He did his postdoctoral studies at The Salk Institute for Biological Studies (CA, USA; 1987-1993). David Mangelsdorf has also been an Investigator of the Howard Hughes Medical Institute (MD, USA) since moving to Dallas in 1993. His current research focuses on understanding the molecular basis of transcriptional signaling by nuclear hormone receptors and exploiting their ligand dependency to discover novel therapeutic options for fighting diseases such as atherosclerosis, gallstone disease, cholestasis, metabolic syndrome, cancer and infectious parasitic diseases. His research team recently discovered a correlation between the expression of two nuclear receptor proteins in non-small-cell lung cancer tissue samples with patients' clinical outcomes. The research features in PLoS Medicine and suggests that the nuclear receptor proteins could serve as therapeutic targets in non-small-cell lung cancer. PMID- 29793246 TI - Plasma fibrinogen as a biomarker in gynecologic cancers. PMID- 29793247 TI - Latest News & Updates from the Personalized Medicine Coalition: Letter from Washington. PMID- 29793250 TI - Personalized medicine for cystic fibrosis: the next generation. PMID- 29793251 TI - An epidemiology of care approach to lab-on-a-chip systems in individualized medicine? AB - Lab-on-a-chip systems (LOCs) are microfluidic systems integrating several laboratory functions on a very small single chip. The identification and characterization of innovative biomarkers based on portable LOCs provides a valuable tool to implement individualized medicine. An analysis of the clinical potential, advantages and obstacles of portable diagnostic LOCs is urgently needed to evaluate the associated risks and opportunities from a healthcare perspective. A planned network project promoted by the federal ministry for education and research in Germany will systematically investigate the scope of LOCs and discuss the impact as well as the future demand, potentially adding to further evidence-based development. PMID- 29793249 TI - Analysis of clinicians' attitudes towards pharmacogenomics. AB - AIM: The use of genetic information to guide a patient's drug therapy will have a great influence on clinical practice within healthcare. However, despite the prospective benefits of pharmacogenetic testing, little is known regarding what clinicians actually think about this promising technology. The purpose of this study was to assess attitudes towards pharmacogenetic testing not previously highlighted within a larger study on clinicians' knowledge and attitudes about pharmacogenetic testing conducted by an interdisciplinary group of researchers at the University of North Carolina at Chapel Hill. MATERIALS & METHODS: The sample included 184 responses to an open-ended question. A thematic analysis of these responses was completed. RESULTS: The thematic analysis identified several themes that were not previously delineated within the original study. The analysis uncovered five additional themes including: application concerns, lack of successful integration, accessibility, potential harm and optimism. CONCLUSION: Future research on the assessment of attitudes of clinicians concerning pharmacogenomics should incorporate these themes. In addition, educational activities conveying knowledge concerning pharmacogenomics needs to become readily available to healthcare providers. Finally, a study that addresses any disparity related to pharmacogenomics needs to be undertaken. PMID- 29793252 TI - Biopharmaceutical industry perspectives on the business prospects for personalized medicine. AB - AIM: Personalized medicine is entering its second decade, yet the role it will play in addressing the biopharmaceutical industry's productivity gap and the rising cost of healthcare is still a matter of speculation. So what does the biopharmaceutical industry itself say about the business prospects for personalized medicine? MATERIALS & METHODS: The authors conducted interviews with 20 science and business experts from 13 companies to find out. In this article, particular attention is paid to drug-diagnostic codevelopment, so-called companion diagnostics. RESULTS: The results of the interviews are discussed in light of perspectives from various stakeholders available from the literature in the public domain. In brief, biopharmaceutical acknowledges the many difficulties that plague this path to product development with particular concern for knowledge gaps in the scientific base, the timing of studies during development, as well as the regulatory, reimbursement and commercial hurdles that can thwart approval, launch and market uptake. CONCLUSION: Nonetheless, personalized medicine in general and companion diagnostics in particular are believed to be an increasingly sustainable business proposition with expectations for rapid market growth in the near term. PMID- 29793253 TI - Treatment for tobacco dependence: a potential application for stratified medicine? AB - Tobacco addiction is a leading preventable cause of death worldwide and places a heavy social and financial burden on society. Therefore, ways of helping people to overcome nicotine dependence are a key element of strategies aimed at improving public health. Current treatments are only partially effective and there is a need to develop more efficient approaches to help smokers to stop. There exists a substantial genetic variability in smoking behavior and the likelihood of cessation - tailoring treatment according to an individual's genetic profile is now technologically feasible and could lead to more successful cessation attempts. Here we review studies of the genetic effects on smoking cessation in randomized controlled trials of pharmacological therapy and discuss the potential value of a personalized approach to help people stop smoking. PMID- 29793254 TI - Towards personalized medicine: exploring the consequences of the effect model based approach. AB - Although personalized medicine has been a subject of research and debate in recent years, it has been underused in medical practice, except in some cancers. We believe that the main reason for the gap between the potential of personalized medicine and its use in daily medical practice can be explained by the lack of an appropriate tool to facilitate the use of biomarker values in a doctor's decision making process. We propose that the effect model could form the basis of such a tool. PMID- 29793255 TI - Analysis of insurance preauthorization requests for BRCA1 and BRCA2 genetic testing: experience of the Humana Genetic Guidance Program. AB - : Published evidence-based guidelines help healthcare providers identify appropriate individuals for BRCA1/2 genetic testing. Health plans often use these guidelines to help make coverage and reimbursement decisions. Humana, a major health plan, launched the Humana Genetic Guidance Program to further facilitate the appropriate use of genetic testing through education. AIM: Identify opportunities to improve medical appropriateness for BRCA1/2 test requests by providing genetic education to providers. MATERIALS & METHODS: BRCA1/2 insurance preauthorization requests submitted to the program were evaluated against guideline-based coverage criteria. RESULTS: In total, 22% of the requests did not meet criteria, and in approximately a quarter of those requests, the clinical history suggested testing for a different cancer syndrome or another affected relative. CONCLUSION: This report demonstrates the program's effectiveness and illustrates the need for additional provider education regarding genetic testing from a payer's perspective. PMID- 29793256 TI - Sustaining development of stratified medicines in the UK healthcare system: a commentary. AB - The UK healthcare system holds a favorable position in the development of stratified medicines through strong scientific innovation, robust biotechnology and pharmaceutical industries and comparatively simple regulatory and reimbursement processes. Organizations such as its robust health technology assessment agency, the NICE and its mature socialized healthcare system, the National Health Service, enable innovative medicines, including stratified treatments for cancer and infectious disease, to be rapidly assessed for their effectiveness and value to patients in the UK. However, our recent observations with a variety of UK healthcare stakeholders suggest that certain features need to be improved if the favorable position in stratified medicine development, and consequential beneficial outcome to patients, is to be sustained and indeed further enhanced to a position of pre-eminence. Key changes suggested are removing healthcare silos and enabling multidisciplinary teams to translate scientific and medical innovation into the best practice; expanding the UK skill base in certain disciplines including medical pathology, health economics and clinical informatics; and using successful pilot cases of stratified medicines to better educate stakeholders in a drive to change healthcare culture. Through this cultural change, the UK would offer healthcare based on prediction and prevention rather than symptom-based diagnosis and reactive treatment. PMID- 29793258 TI - The Personalized Medicine Coalition - 8 months on. AB - Edward Abrahams is the Executive Director of the Personalized Medicine Coalition (PMC), a nonprofit educational and advocacy group encompassing a broad range of academic, industrial, patient and healthcare provider constituencies. As a former Executive Director of the Pennsylvania Biotechnology Association, Assistant Vice President for Federal Relations at the University of Pennsylvania, and a legislative assistant and economist for the United States Congress, he brings an extensive knowledge of industry, academia and government to the coalition. PMID- 29793257 TI - A critical view of the general public's awareness and physicians' opinion of the trends and potential pitfalls of genetic testing in Greece. AB - AIM: Progress in deciphering the functionality of the human genome sequence in the wake of technological advances in the field of genomic medicine have dramatically reduced the overall costs of genetic analysis, thereby facilitating the incorporation of genetic testing services into mainstream clinical practice. Although Greek genetic testing laboratories offer a variety of different genetic tests, relatively little is known about how either the general public or medical practitioners perceive genetic testing services. MATERIALS & METHODS: We have therefore performed a nationwide survey of the views of 1717 members of the general public, divided into three age groups, from all over Greece, and residing in both large and small cities and villages, in order to acquire a better understanding of how they perceive genetic testing. We also canvassed the opinions of 496 medical practitioners with regard to genetic testing services in a separate survey that addressed similar issues. RESULTS: Our subsequent analysis indicated that a large proportion of the general public is aware of the nature of DNA, genetic disorders and the potential benefits of genetic testing, although this proportion declines steadily with age. Furthermore, a large proportion of the interviewed individuals would be willing to undergo genetic testing even if the cost of analysis was not covered by healthcare insurance. However, a relatively small proportion of the general public has actually been advized to undergo genetic testing, either by relatives or physicians. Most physicians believe that the regulatory and legal framework that governs genetic testing services in Greece is rather weak. Interestingly, the vast majority of the general public strongly opposes direct-access genetic testing, and most would prefer referral from a physician than from a pharmacist. CONCLUSION: Overall, our results provide a critical evaluation of the views of the general public with regard to genetics and genetic testing services in Greece and should serve as a model for replication in other populations. PMID- 29793259 TI - The use of pharmacogenetics in the treatment of asthma. AB - Stephen Holgate holds a Medical Research Council Clinical Research Chair in Immunopharmacology at the University of Southampton (UK). A former adviser to the House of Lords Select Committee on Science and Technology, he is also the recipient of numerous honors and awards. He is the author of over 800 peer reviewed papers, co-editor of Clinical and Experimental Allergy, and is currently co-Chair of the National Allergy Strategy group. His research focuses on the cellular and mediator mechanisms of allergy and asthma, particularly focusing on applications for diagnosis and treatment. PMID- 29793260 TI - Ciphergen's Diagnostic Division. AB - The Diagnostics Division is the commercialization engine for Ciphergen Biosystems, Inc. Their goal is to identify, develop and commercialize high-value proteomic-based assays that will meet the clinical needs of physicians as they diagnose, treat and monitor their patients. Initially, the Diagnostics Division is focusing its efforts on cancer, cardiovascular disease and Alzheimer's disease. PMID- 29793261 TI - Exchanging genetic data for public health practice and human subjects research: implications for health practitioners. AB - Advances in genomic science and medicine require collaboration between healthcare providers, researchers and public health practitioners to improve individual and communal health. However, broader collaboration raises significant privacy and other concerns about acquisitions, uses and disclosures of identifiable genetic data. Corresponding legal requirements vary extensively if data are to be used in clinical practice, human subjects research, or public health surveillance. Distinguishing between practice and research activities is not easy. We introduce an enhanced methodology to distinguish public health practice from human subjects research to: help providers, researchers, and public health practitioners navigate the legal requirements underlying the exchange of genetic information; determine when public health data use crosses over to research, thereby triggering differing legal and ethical regulations; and to protect individual and group privacy from the unintended misuse of genetic information. PMID- 29793263 TI - Food & Drug Administration panel approves heart failure medication aimed at African-Americans. PMID- 29793262 TI - The implications of electronic health records for personalized medicine. AB - The emerging concept of an electronic health record (EHR) targeted at a patient centric, cross-institutional and longitudinal information entity (possibly spanning the individuals lifetime) has great promise for personalized medicine. In fact, it is probably the only vehicle through which we may truly realize the personalization of medicine beyond population-based genetic profiles that are expected to become part of medication and treatment indications in the near future. The new EHR standards include mechanisms that integrate clinical data with genomic testing results obtained through applying research-type procedures, such as full DNA sequencing, to an individual patient. Although the most optimal process for the utilization of integrated clinical-genomic data in the EHR framework is still unclear, the new Health Level Seven (HL7) Clinical Genomics Draft Standard for Trial Use suggests using the 'encapsulate & bubble-up' approach, which includes two main phases: the encapsulation of raw genomic data and bubbling-up the most clinically significant portions of that data, while associating it with clinical phenotypes residing in the individual's EHR. PMID- 29793264 TI - Cytochrome P450 gene-based drug prescribing and factors impacting translation into routine clinical practice. AB - Pharmacogenetics represents a rapidly advancing, competitive field of investigation. Due to the potential for clinically recognizable interactions between a set of old polymorphic genes and a relatively new environmental insult (drugs), many human geneticists believe that variability in the drug-metabolizing enzyme systems will soon translate into clinical practice across entire populations. Despite this, the field has not yet received widespread clinical acceptance. This article will review the common cytochrome P450 gene polymorphisms and discuss the factors that may facilitate (or attenuate) their translation into clinical practice. PMID- 29793265 TI - HLA-B genotyping to detect carbamazepine-induced Stevens-Johnson syndrome: implications for personalizing medicine. AB - Preventing severe adverse drug reactions by identifying people at risk with a simple genetic test is the goal of many pharmacogenomic studies. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are related, life-threatening cutaneous adverse reactions, most often caused by medication. The overall incidence and the commonly offending drugs vary among different ethnic populations. Susceptibility to such idiosyncratic reactions is thought to be genetically determined and immune mediated. Finding a strong genetic association between a particular human leukocyte antigen (HLA)-B allele and the reaction to a specific drug provides evidence that the pathogenesis of the severe cutaneous adverse drug reactions involves major histocompatibility complex-restricted presentation of a drug or its metabolites for T-cell activation. In the case of carbamazepine-induced SJS/TEN, the tight association of the HLA-B*1502 allele (sensitivity 100%, specificity 97% and odds ratio 2504) provides a plausible basis for further development of such a test to identify individuals at risk of developing this life-threatening condition. PMID- 29793266 TI - Biomarker World Congress 2005. PMID- 29793268 TI - New Chinese biobank set to be largest in world. PMID- 29793267 TI - Personalizing public health. PMID- 29793269 TI - The biospecimen as the key to personalizing medicine. PMID- 29793270 TI - Regulating personal data in a shared world: limitations of the EU's approach to data protection. AB - A personalized interaction, in an increasingly information-rich environment, is increasingly unlikely to be shaped by information about only the persons directly involved. As data about others is related to an individual, and perceptions about that individual formed accordingly, it is important that data-protection regulation takes into account the shared nature of personal data. The European Data Protection Directive provides an important standard for data sharing between countries. Therefore, it is essential to realize any limitations in its approach when data might be said to relate to more than one person. The need to address any such limitation becomes all the more urgent as more genetic databases and biobanks are established around the world and movements are made towards data sharing between them. Not only is it important that the regulation of genetic data takes into account its shared nature, but as international collaboration relies upon agreed standards, it is important that it does so quickly. PMID- 29793271 TI - From farm to pharma: public health challenges of nutrigenomics. AB - Nutrigenomics is speculated to be the next big dimension of genomic sciences geared toward improving public and personal health through nutritional and dietary interventions. This article traces how public health nutrition has been used as an agenda both in agriculture genomics and now in biomedicine. The centrality and importance of food in health and well-being is well recognized and, with the developments in genomics, it has also been used as a tool for public health-related policies and commercialization. This perspective discusses nutrigenomics from four public health perspectives; novel foods and the public health agenda; the epidemic of lifestyle-related diseases, such as obesity, diabetes and cardiovascular diseases; commercialization; and conceptual issues. Several ethical and governance issues in applying nutrigenomics to public health and the implications for public policy will also be considered. PMID- 29793272 TI - Uses of the Twins UK genetic database. AB - Tim Spector is a Professor of Genetic Epidemiology at King's College London and Director of the Twin Research and Genetic Epidemiology Unit at St Thomas' Hospital, London. Professor Spector graduated from St Bartholomew's Hospital Medical School, London, in 1982. After working in General Medicine, he completed a MSc in Epidemiology, and his MD degree at the University of London in 1989. He founded the UK Twins Registry of 10,000 twins in 1993, which is one of the largest collections of genotype and phenotype information on twins worldwide, whose breadth of research has expanded to cover a wide range of common complex traits many of which were previously thought to be mainly due to aging and the environment. He has published over 350 research articles on common diseases. He has written several original articles on the genetics of a wide range of diseases and traits including back pain, acne, inflammation, obesity, memory, musical ability and sexuality. He is the principal investigator of the EU Euroclot and Treat OA study, and a partner in five others. He has written several books, focusing on osteoporosis and genetics and, in 2003, he published a popular book on genetics: Your Genes Unzipped. PMID- 29793273 TI - Academic and commercial genetic testing laboratories: complementary if not complimentary. AB - The new century has introduced a myriad of changes in the practice of clinical and laboratory genetics. As molecular diagnostics entered the mainstream of current medical practice, a number of academic genetic laboratories faced intense financial pressure and many succumbed. Although the entry of commercial laboratories into the genetic testing arena is one factor in this process, it is by no means the only one. Increased regulatory requirements, changes in funding sources for academic institutions, and the rise of large managed care organizations also have culpability. Many academic laboratory directors have expressed hostility toward commercial laboratories, both vocally at genetic meetings and in publications. This vitriol serves no one. Commercial laboratories are here to stay and, in fact, provide important services to American healthcare consumers by making esoteric molecular diagnostic testing widely available. Rather than throw stones at each other, it is time for academic and commercial laboratories to coexist and realize that each has strengths and, most importantly, that patients are best served by cooperation, not confrontation between these equally competent groups. This article examines the historical antecedents to the current conflictive situation and offers suggestions for collaborative efforts in the future. PMID- 29793274 TI - Role of UGT1A1*6 in irinogenetics in Asians. AB - Evaluation of: Jada SR, Lim R, Wong CI et al.: Role ofUGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. 98(9), 1461-1467 (2007). The pharmacokinetics and toxicity of irinotecan vary widely among patients. This review focuses primarily on a study of the role of UGT1A1*6, UGT1A1*28, and ABCG2 421C>A in three Asian cancer patient populations treated with a 3-weekly regimen of irinotecan. In that study, a statistically significantly higher level of SN-38 and a relatively lower degree of glucuronidation occurred in patients with the UGT1A1*6 homozygote genotype than in patients with the reference genotype. The UGT1A1*6 allele was associated with an increased risk of severe neutropenia. In addition, the study of gene allele frequencies in three healthy Asian populations indicated that the allelic frequency of UGT1A1*6 was higher in the healthy Chinese subjects than in the Malaysian or Indian subjects. UGT1A1*28 and ABCG2 421C>A were not associated with the pharmacokinetics of SN-38 or the severity of neutropenia. In this evaluation, we put this study into the context of similar studies of irinogenetics (irinotecan pharmacogenetics) in Asians and discuss the application of UGT1A1 testing in Asian cancer patients treated with irinotecan-containing regimens. PMID- 29793275 TI - Insurance coverage for pharmacogenomic testing in the USA. AB - The completion of the Human Genome Project has led to claims that we are on the verge of entering the era of 'personalized medicine'. Some initial, highly visible successes have positioned pharmacogenomics as the poster child for this new era. Many commercial referral laboratories are offering pharmacogenomic assays. In the US healthcare system, payers have had a significant impact on utilization of new drugs and technologies. Payers are frequently characterized as a barrier to the rapid dissemination of innovative therapies. In reality, payers are frequently the only group that scrutinize these new therapies for utility. As such, they play a critical role in assuring that their members are receiving appropriate care. PMID- 29793276 TI - Translating from the laboratory to the patient: a multidisciplinary approach to delivering individualized therapy. PMID- 29793277 TI - Balancing benefits of human genetic research against civic concerns: Essentially Yours and beyond - the case of Australia. AB - Large human genetic databases, especially those that are biomedical and forensic, have emerged since the completion of the Human Genome Project. However, this development has occurred in a time of intense public ambivalence to life science and genomics innovations. Controversies revolve around genetic modification, stem cell technologies and human genetic databases. Debate about databases focuses on how to balance the benefits from genetic research against civic concerns, typically, privacy and unfair discrimination and, more recently, public trust. In 1989, Australian jurisdictions began developing regulatory standards for human genetic databases but from the start these lacked uniformity and adequate scope. Enduring concerns led to a widescale public inquiry (2001-2003), which produced the Essentially Yours report. However, while the Australian government supports many of the report's recommendations, civic concerns remain as policy responses are checkered. In this special report, we reflect on the debate, the rise of the inquiry, its recommendations and policy responses, and competency and trust in regulation. PMID- 29793278 TI - 'Private fears in public places?' Ethical and regulatory concerns regarding human genomic databases. PMID- 29793279 TI - Banking expectations: the promises and problems of biobanks. AB - In the last decade, governments, medical charities, pharmaceutical companies and disease advocacy organizations have spent considerable time and money developing biobanks to aid drug discovery and the investigation of disease. This article identifies and assesses the various expectations that have driven the investment in different types of biobanks. It suggests that they have been the focus of unrealistic promises about producing a 'biobank revolution' that will transform biomedicine and healthcare. We need more modest expectations about what can be achieved, and need to tackle certain conceptual and methodological challenges for biobanks to fulfill their potential. PMID- 29793280 TI - Health record banks: integrating clinical and genomic data into patient-centric longitudinal and cross-institutional health records. PMID- 29793281 TI - Theranostics Health: personalized therapy and diagnosis today. AB - Theranostics Health is a young company using mature proprietary technology to make personalized medicine possible today. The firm provides pharmaceutical scientists, clinical trial clinicians and treating physicians with highly detailed portraits of protein drug target pathways and critical patient data about drug activity, selectivity and specificity. Its assays and therapeutic tools provide unprecedented cancer treatment and drug response information and show strong prospects for application to a wide range of disease indications. Theranostics' leadership believes that its products and services will have major impact on individualized therapeutic efficacy and treatment toxicity, while reducing treatment and drug-development costs and expediting the introduction of new pharmaceutical solutions. PMID- 29793282 TI - Pharmacogenetics of oral anticoagulants: the opportunity for individualized drug treatment of greater safety. AB - Oral antivitamin K (AVK) anticoagulants are widely prescribed for the prophylaxis and treatment of a number of thromboembolic disorders. They constitute a major cause of iatrogenic accidents because of their narrow therapeutic index and consequently increase both thrombotic and bleeding risk; thus, regular monitoring is required. Patient and environmental factors affect the anticoagulation response and it has become evident that the wide interindividual variation in AVK response is also partly genetically determined. The main enzyme responsible for the metabolism of AVKs is hepatic cytochrome P450 CYP2C9. Vitamin K epoxide reductase complex subunit I (VKORC1) is a key enzyme in the vitamin K cycle; it is required to regenerate the cofactor essential for the activation of vitamin K dependent clotting factors and is the target enzyme of AVK inhibition. Genetic variations affecting both CYP2C9 and VKORC1 are associated with variability in drug response and may explain differences in dose requirements. Genotyping for CYP2C9 and VKORC1 variants before initiation of treatment could allow clinicians to develop dosing protocols and identify patients at higher risk for AVK complications such as bleeding. PMID- 29793284 TI - Microsoft(r) announces the formation of the BioIT Alliance to accelerate the development of personalized medicine. PMID- 29793283 TI - Pharmacogenomics and antihypertensive drugs: a path toward personalized medicine. AB - Pharmacogenomics focuses on genes and the transcriptome and proteome. It has the potential to enhance healthcare management by improving disease diagnosis and implementing treatments adapted to each patient. Previously, pharmacogenetics of candidate genes focused on clinical research. It is now extended by using genome wide approaches to elucidate the inherited basis of differences between individuals in their response to drugs. We summarize relevant polymorphisms of genes involved in the pharmacokinetics and pharmacodynamics of antihypertensive drugs and we give an overview of the state of pharmacogenomic research in hypertension medicine. Even if things are getting better, current pharmacogenetic studies still lack power, adequate selection of candidate genes and knowledge of their functions at the physiological level. Finally, some specific end point phenotypes (i.e., peptides or proteins related to the metabolic cycle targeted by the drug) should be integrated to propose data that are easily applicable to personalized medicine. PMID- 29793285 TI - The future may be closer than you think: a response from the Personalized Medicine Coalition to the Royal Society's report on personalized medicine. AB - A recent report from the British Royal Society on the prospects for personalized medicine provides a sobering assessment of the field and its prospects. The report contends that pharmacogenetics has little clinical relevance at the moment and will only progress with the completion of large, cumbersome clinical trials. The report goes on to note that the regulatory infrastructure, medical education initiatives and public deliberation necessary to make personalized medicine a reality are essentially nonexistent, at least so far. In our view, personalized medicine is much more than a hypothetical protocol designed to correlate genotypes with prescriptions. We argue that the development of personalized medicine is a broader phenomenon that is already being practiced in one form or another in many contexts. Both academic medicine and the pharmaceutical industry have a huge stake in bringing pharmacogenetic-based personalized medicine to fruition; we expect both entities to act as drivers of what will be a long-term, iterative process. PMID- 29793286 TI - Personalized medicine: new perspectives - new ethics? AB - Are new concepts in biomedical ethics required to keep pace with the developments in post-Human Genome Project (HGP) genomics? This paper traces the place of ethics in the post-HGP landscape. The need for a revision of the approach taken by biomedical ethics toward questions in genomics has been appreciated for years. Traditional biomedical ethics, led by the protection paradigm, was devised to serve a very different context. Today, compelling ethical questions arise from the tension between individual and collective interests in the context of population-based data collection and research. The collection of phenotype data, and the development of new sequencing technologies, raises burning questions that call for innovative tools and models in ethics. Future developments that will likely include the routine availability of personal genome information, and the advent of systems biology as a framework for interpretation, will require ongoing flexibility and a creative approach. PMID- 29793287 TI - Nucleic acid quantification and disease outcome prediction in colorectal cancer. AB - Histopathological stage at diagnosis remains the most important prognostic determinant for colorectal cancer. However, conventional staging is unable to predict disease outcome accurately for each individual patient. This results in considerable prognostic heterogeneity within a given tumor stage and is of particular relevance for a subgroup of patients with stage II disease that would benefit from adjuvant therapy. The recent advances in functional genomics are beginning to have a significant impact on clinical oncology, and there is widespread interest in using molecular techniques for clinical applications. These have focused on two approaches: the use of polymerase chain reaction (PCR) based methods for the detection of occult disease in lymph nodes, bone marrow and blood and the use of microarrays for the expression profiling of primary tumors. The aim is to develop molecular classifiers that will allow the prediction of disease outcome, thus matching patients with individualized treatment. Despite the obvious attractions of these approaches, there have been significant technical, biological and analytical problems in their translation into clinically relevant practice. This is particularly true for colorectal cancer, the second most common cancer in the western world. Nevertheless, progress is being made and the improved awareness and appreciation of those difficulties is beginning to generate results that should prove useful for clinical oncology. PMID- 29793288 TI - High carrier prevalence of deficient and null alleles of CYP2 genes in a major USA hospital: implications for personalized drug safety. AB - Many drugs are metabolized by highly polymorphic cytochrome P450 (CYP) enzymes. Among these enzymes, members of the CYP2 family coded by the CYP2D6, CYP2C9 and CYP2C19 genes are best amenable to the precise prediction of an individual's innate capacity to metabolize drugs by DNA typing of inherited null and deficient alleles. We determined the frequency of these alleles and the prevalence of their carriers in a New England, USA, tertiary care center to assess underlying population genetic features for the practice of personalized medicine. We determined that 54, 25 and 27% are carriers of at least one deficient or null allele for the CYP2D6, CYP2C9 and CYP2C19 genes, respectively. Furthermore, 6% of individuals are carriers of two null alleles for CYP2D6 and are predicted to have no biochemical activity for this isoenzyme. These results support the implementation of DNA typing of CYP2 genes to diagnose adverse drug reactions and to prevent a substantial number of patients being prescribed drugs they cannot adequately metabolize. PMID- 29793289 TI - Application of TDM, pharmacogenomics and biomarkers for neurological disease pharmacotherapy: focus on antiepileptic drugs. AB - Anticonvulsants, or antiepileptic drugs (AEDs), are a vital tool in the therapeutic management of epilepsy patients. However, many AEDs are commonly used in the management of nonepileptic conditions, such as chronic pain, migraine headaches and psychiatric disorders. It is well documented that serum drug levels are an important data tool for the management of patients taking these drugs. As we move toward the personalized optimization of pharmacotherapy, drug level data will not be sufficient. This article will review tools for therapeutic drug management of AEDs including pharmacogenetics and biomarkers, in addition to traditional serum drug levels. PMID- 29793290 TI - Pharmacogenomics in the treatment of rheumatoid arthritis: clinical implication and perspective. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease. The inflammatory process of the joint destroys articular architecture and causes a significant disability. The efficacy of disease modifying antirheumatic drugs such as methotrexate, sulfasalazine and biological response modifiers, is widely accepted. However, the outcome of the treatment with these agents is known to vary among patients. The application of the pharmacogenomics is expected to reduce toxicities and enhance the desirable effects of therapeutic agents for RA. Recently, pharmacogenomic studies on methotrexate, sulfasalazine and tumor necrosis factor-alpha inhibitors have been reported. These investigations suggest that the pharmacogenomic approach is useful for the treatment of RA, although there are points to be considered before the translation of the pharmacogenomic data into clinical practice. This review focuses on the latest information on the pharmacogenomics of antirheumatic drugs and its clinical implication in the treatment of RA. PMID- 29793291 TI - Past, present and future of gene expression-tailored therapy for lung cancer. AB - "Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease." Sir William Osler (1849-1919). All human beings are different and some of these differences are the variations in response to xenobiotics. Personalized medicine means: the right patient population, the right drug, the right dose, the right indication, and administration at the right time. This review provides an update on concepts of personalized therapy for lung cancer. PMID- 29793292 TI - Genome-based biomarkers for adverse drug effects, patient enrichment and prediction of drug response, and their incorporation into clinical trial design. AB - Classic examples of pharmacogenomic biomarkers for drug efficacy include genetic variation in the drug target (including its expression level) and drug metabolizing enzymes (DMEs). Recent US FDA approvals of tests for cytochrome P450 2D6/2C9 and uridine diphosphate glucuronsyltransferase (UGT)1A1 have given regulatory endorsement to biomarkers that can improve drug safety by identifying individuals at risk for drug toxicity. Markers that predict risk for disease can identify patients who will have a greater than average benefit from therapy. This creates a new opportunity to enrich clinical trials with patients who are likely to have more events and to achieve earlier drug approval. Markers that predict for risk of cardiovascular, thrombotic and liver diseases may also identify a subset of individuals at substantially elevated risk for adverse drug effects. The adaptive clinical trial design provides a mechanism for incorporating genomic information during clinical trials, while providing sufficient time for diagnostic product development and co-registration with a new drug application. PMID- 29793293 TI - Challenges and opportunities of pharmacogenetics in drug development. AB - Drugs fail the regulatory process for a variety of reasons, including issues with pharmacokinetics, safety and efficacy. One of the most exciting questions in drug development today is how far the science of pharmacogenetics, the study of the genetics of drug response, can be used to address the fundamental issues that the pharmaceutical industry is facing. In particular, the question of how far it is possible to use this emerging science to deliver the right treatment, to the right patient, at the right dose, at the right time is both the challenge and opportunity of using pharmacogenetics in drug development. This review will address these questions with several real-life examples. PMID- 29793294 TI - Pharma, clinicians and the lab come together over personalized medicine. PMID- 29793295 TI - Pharmacogenomics: single genes, whole genomes and global networks. PMID- 29793296 TI - Medicine, genetics and race: the case of cardiovascular diseases. PMID- 29793297 TI - From human genetic variations to prediction of risks and responses to drugs and the environment. PMID- 29793298 TI - Gene mutation increases risk of late-onset Alzheimer's disease. PMID- 29793299 TI - Development of a warfarin-dosing algorithm in Asian patients: a pharmacogenomic approach. AB - Evaluation of: Tham LS, Goh BC, Nafziger A et al.: A warfarin-dosing model in Asians that uses single nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9. Clin. Pharmacol. Ther. 80, 346-355 (2006) [1] . Large interindividual variability exists in warfarin dose requirements and the development of genotype-guided dosing algorithms that accurately predict warfarin doses is of considerable interest. Tham and colleagues used specific CYP2C9 and VKORC1 polymorphisms, along with clinical factors, to build an algorithm to accurately estimate warfarin doses in a multi-ethnic Asian population. The final model accounted for 60.2% of the overall variability in warfarin dose requirements. In a separate validation cohort, the model accurately estimated warfarin doses with a correlation of 0.73 between actual and model-predicted doses. The next step in warfarin pharmacogenomic research is to take warfarin dosing algorithms, such as the one developed in this study, and use them in prospective, randomized studies in order to determine whether genotype-guided warfarin dosing is better than the traditional care approach. PMID- 29793300 TI - Personalized medicine: the absence of 'model-changing' financial incentives. AB - This perspective biases on the side that personalized medicine can contribute to a more efficient collective model; however, the hard economics need and deserve significantly more critical analysis and new data input than they are currently being given, to determine their role, or not, in driving change. Put simply, as with the birth of all new and promising developments in healthcare, myth, hope and trend-spotting are driving this market forward, rather than any hard evidence of a sustainable commercial business model for all stakeholders. While there are clear economic benefits to aspects of delivery along the way to personalized care, there may in fact be no compelling economic drivers for radical change for payers and the pharmaceutical industry. The best they can hope to achieve is that the balance sheet is, just that, in balance. PMID- 29793301 TI - Risk-based and diagnostics-linked personalized medicine for cancer. AB - Personalized medicine is gaining momentum in healthcare by allowing physicians to determine an individual's predisposition to different diseases and to better diagnose and treat those diseases. Personalized medicine is frequently described as the right drug for the right patient at the right time; that is, a physician will prescribe treatment based on the individual characteristics of each patient such that the patient is likely to respond to a particular treatment with minimal adverse events. The heterogeneity of cancer makes the implementation of personalized medicine a necessity. PMID- 29793302 TI - Individualizing warfarin therapy. AB - Warfarin is the most commonly prescribed oral anticoagulant for the treatment and prevention of thromboembolic events. The correct maintenance dose of warfarin for a given patient is difficult to predict, the drug carries a high risk of toxicity, and variability among patients means that the safe dose range differs widely between individuals. Recent pharmacogenetic studies indicate that the routine incorporation of genetic testing into warfarin therapy protocols could substantially ease both the financial and health risks currently associated with this treatment. In particular, the variability in warfarin dose requirement is now recognized to be due, in large part, to polymorphisms in two genes: cytochrome P450 2C9 and the vitamin K epoxide reductase complex subunit 1. The development of algorithms that integrate all of the relevant genetic and physical factors into comprehensive, individualized predictive models for warfarin dose could be used to translate the results of pharmacogenetic testing into actionable clinical application. PMID- 29793303 TI - Age-related genetic abnormalities: the Achilles' heel for customizing therapy in elderly lung cancer patients. AB - Aging and cancer are closely related, and DNA repair systems, mainly involving the nucleotide excision repair pathway, have an important caretaker function in both processes. More than half of non-small cell lung cancer patients are elderly, and the expression of some genes involved in the mitotic checkpoint, such as BubR1, declines with aging. Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer; if performance status is good, both elderly and younger patients can tolerate this treatment equally well. Customized cisplatin treatment, based on reduction of the nucleotide excision repair pathway function, could be an attractive approach, and the assessment of mitotic checkpoint genes can be used for selecting docetaxel treatment. Epidermal growth factor receptor (EGFR) mutations are particularly frequent in elderly lung cancer patients who are never-smokers and constitute an attractive target for treatment with EGFR tyrosine kinase inhibitors. PMID- 29793304 TI - Mass spectrometry-based tissue proteomics for cancer biomarker discovery. AB - There is an urgent need for the development of technologies that allow the monitoring of protein expression and processing in tumor tissues resulting from development, physiology and disease state. To address the issue of cell heterogeneity in the tissue section, several microdissection techniques have been developed to provide a rapid and straightforward method for isolating selected subpopulations of cells for downstream molecular analysis. Development and demonstration of an effective discovery-based proteome platform, Gemini, are particularly highlighted for its capabilities of achieving ultrasensitive and comprehensive analysis of minute proteins extracted from targeted cells in tissue specimens. The greatest expectations for targeted proteomics research using enriched nonmalignant and malignant cells from high-quality fresh-frozen, formalin-fixed and paraffin-embedded specimens reside in the identification of diagnostic, prognostic and predictive biological markers in the clinical setting, as well as the discovery and validation of new protein targets in the biopharmaceutical industry. PMID- 29793305 TI - Changes in the editorial team and innovations at Social Science & Medicine. PMID- 29793306 TI - A social movement, based on evidence, to reduce inequalities in health. PMID- 29793309 TI - Astragaloside IV protects against the pathological cardiac hypertrophy in mice. AB - Although pathologic hypertrophic hearts currently maintain output, sustained cardiac hypertrophy could predispose a patient to arrhythmia and sudden death, and also cause heart failure. Thus, finding effective treatment and exploring the underlying molecular mechanisms of cardiac hypertrophy is urgently necessary. Astragaloside IV (AST-IV) is the main active component, extracted from the traditional Chinese medicinal herb Astragalus membranaceus. Previous studies have indicated that AST-IV has various bioactivities, such as anti-cancer, anti oxidative stress and anti-inflammation. In the present study, we aimed to explore the effects of AST-IV on cardiac hypertrophy induced by aortic banding (AB) surgery in mice, and to reveal the underlying signaling mechanisms. The suppressor of IKKepsilon (SIKE) is a negative regulator of the interferon pathway, which could be enhanced by AST-IV to ameliorate pathological cardiac hypertrophy in mice through inactivating TANK-binding kinase 1 (TBK1)/PI3K/AKT signaling pathway. AST-IV attenuated cardiac hypertrophy, collagen accumulation and abnormal cardiac functions. In addition, AB-induced apoptosis and inflammation in the heart tissue samples of mice, which were attenuated by AST-IV administration through inhibiting SIKE expression levels. Together, the findings above indicated that AST-IV might be a potential candidate to prevent cardiac hypertrophy via elevating SIKE to suppress TBK1/PI3K/AKT activity. PMID- 29793310 TI - MiR-142 inhibits cecal ligation and puncture (CLP)-induced inflammation via inhibiting PD-L1 expression in macrophages and improves survival in septic mice. AB - This study aims to explore the roles of miR-142/PD-L1 axis in cecal ligation and puncture (CLP)-induced inflammation and the survival in septic mice. Here, miR 142 was found to be decreased in sepsis patients. And miR-142 was decreased but PD-L1 was increased in CLP-treated mice macrophages in a time-dependent manner. Mechanistically, miR-142/PD-L1 regulatory axis was identified in macrophages. Pre injection of miR-142 agomir following CLP treatment attenuated CLP-induced inflammation, characterized as the downregulation of IL-2 and TNF-alpha secretion, but this effect could not be ameliorated by post-injection of miR-142 agomir after CLP treatment. Additionally, PD-L1 overexpression enhanced CLP induced inflammation and reversed miR-142-mediated inhibition on CLP-induced inflammation in macrophages. Importantly, CD4+T/CD8+T cell ratio was markedly increased in the peripheral blood of CLP-treated mice, which was attenuated by pre-injection of miR-142 agomir. Moreover, pre-injection of miR-142 agomir or aPD L1 decreased CLP-induced mortality. Therefore, our results indicate that miR-142 could attenuate CLP-induced inflammation and thus sepsis via targeting PD-L1 in macrophages. PMID- 29793311 TI - The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats. AB - Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously, chemotherapeutic agents have been reported to cause permanent azoospermia and infertility in men. Methotrexate has been also shown to damage the seminiferous tubules of the testicles, lower the sperm count, and cause genetic mutations (in DNA) in sperm. In this study, we aimed to investigate the protective effects of alpha lipoic acid (ALA) on MTX induced testicle damage in a rat model. A total of 40 male Wistar Albino rats were used in this study. The rats were divided into four groups including 10 rats in each. The first group (control group) received only saline intraperitoneal (i.p.); the second group (ALA group) was given ALA 100 mg/kg i.p.; the third group (MTX group) received single dose MTX 20 mg/kg i.p.; and the fourth group (MTX + ALA group) received single dose MTX 20 mg/kg i.p. and ALA 100 mg/kg i.p. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) levels in the testicular tissue and serum testosterone, serum total antioxidant status (TAS) and total oxidant status (TOS) levels were biochemically evaluated. Testicular tissues histopathologically evaluated. In the MTX group, the MDA, TAS and TOS levels were higher, while the SOD, CAT, GPx, MPO and serum testosterone levels decreased. Compared to the MTX group, the MDA, TAS and TOS levels were lower and the SOD, CAT, GPx, MPO and serum testosterone levels increased in the MTX + ALA group. In the histopathological examination, the mean seminiferous tubule length (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were found to significantly decrease in the MTX group, compared to the control group. These values were significantly higher in the MTX + ALA group, compared to the MTX group (p < 0.05). In our experimental study, MTX caused severe tissue destruction in testicles by increasing the formation of free oxygen radicals. Based on our study results, we suggest that, as a potent free radical scavenger, ALA can reduce MTX-induced testicular tissue damage thanks to its antioxidant and anti-inflammatory properties. PMID- 29793312 TI - Aberrant DNA methylation of key genes and Acute Lymphoblastic Leukemia. AB - DNA methylation is a dynamic process influencing gene expression by altering either coding or non-coding loci. Despite advances in treatment of Acute Lymphoblastic Leukemia (ALL); relapse occurs in approximately 20% of patients. Nowadays, epigenetic factors are considered as one of the most effective mechanisms in pathogenesis of malignancies. These factors are reversible elements which can be potentially regarded as therapy targets and disease prognosis. DNA methylation, which primarily serves as transcriptional suppressor, mostly occurs in CpG islands of the gene promoter regions. This was shown as a key epigenetic factor in inactivating various tumor suppressor genes during cancer initiation and progression. We aimed to review methylation status of key genes involved in hematopoietic malignancies such as IKZF1, CDKN2B, TET2, CYP1B1, SALL4, DLC1, DLX family, TP73, PTPN6, and CDKN1C; and their significance in pathogenesis of ALL. The DNA methylation alterations in promoter regions of the genes have been shown to play crucial roles in tumorigenesis. Methylation -based inactivation of these genes has also been reported as associated with prognosis in acute leukemia. In this review, we also addressed the association of gene expression and methylation pattern in ALL patients. PMID- 29793313 TI - Therapeutic effects of scoparone on pilocarpine (Pilo)-induced seizures in mice. AB - Epilepsy is a common and devastating neurological disorder. Inflammatory processes and apoptosis in brain tissue have been reported in human epilepsy. Scoparone (6,7-dimethoxycoumarin) is an important chemical substance, which has multiple beneficial activities, including antitumor, anti-inflammatory and anti coagulant properties. In our present study, we attempted to investigate if scoparone could attenuate seizures-induced blood brain barrier breakdown, inflammation and apoptosis. Pilocarpine (Pilo) and methylscopolamine were used to establish acute seizure animal model. Scoparone suppressed the leakage of blood brain barrier, inflammation and apoptosis. In hippocampus and cortex, the expression of inflammation-associated molecules, such as chemokine (CXC motif) ligand 1 (CXCL-1), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF alpha), IL-6, hypoxia-inducible factor 1alpha (HIF-1alpha), and monocyte chemoattractant protein-1 (MCP-1), were reduced by scoparone through inactivating toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kappaB) pathway. Scoparone reduced apoptotic levels in hippocampus by TUNEL analysis, along with decreased Caspase-3 and PARP cleavage. In addition, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in Pilo-induced acute seizures was also inactivated by scoparone. In vitro, we confirmed that scoparone inhibited LPS-caused astrocytes activation as proved by the reduced glial fibrillary acidic protein (GFAP) levels, inflammation and apoptosis, which were at least partly dependent on AKT suppression. The results above indicated that scoparone could relieve pilocarpine (Pilo)-induced seizures against neural cell inflammation and apoptosis. PMID- 29793314 TI - Embelin-loaded oral niosomes ameliorate streptozotocin-induced diabetes in Wistar rats. AB - Embelin is a natural compound possessing a plethora of pharmacological activities, including antidiabetic activity. When formulated as niosomes, embelin offers additional advantages of nanoformulations and can be further exploited for clinical use. An oral niosome formulation of embelin was developed using a thin film hydration technique, and its antidiabetic activity was studied. The formulation was characterized in terms of entrapment efficiency, vesicle size and morphology, in vitro release profile, and stability. Antidiabetic evaluation was performed in streptozotocin (STZ)-induced diabetic Wistar rats. An antioxidant assay was carried out by evaluating superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), and glutathione (GSH). The optimized formulation showed a significant hypoglycemic effect, which was comparable with that of repaglinide. Moreover, significant increases in SOD, CAT, and GSH, along with a decrease in the lipid peroxidation level, were observed, which confirmed the antioxidant efficacy of the formulation. Thus, it is evident that the embelin-loaded niosome formulation was efficacious in diabetes management in Wistar rats. PMID- 29793315 TI - Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world. AB - In recent years nanotechnology has revolutionized the healthcare strategies and envisioned to have a tremendous impact to offer better health facilities. In this context, medical nanotechnology involves design, fabrication, regulation, and application of therapeutic drugs and devices having a size in nano-range (1-100 nm). Owing to the revolutionary implications in drug delivery and gene therapy, nanotherapeutics has gained increasing research interest in the current medical sector of the modern world. The areas which anticipate benefits from nano-based drug delivery systems are cancer, diabetes, infectious diseases, neurodegenerative diseases, blood disorders and orthopedic problems. The development of nanotherapeutics with multi-functionalities has considerable potential to fill the lacunae existing in the present therapeutic domain. Nanomedicines in the field of cancer management have enhanced permeability and retention of drugs thereby effectively targeting the affected tissues. Polymeric conjugates of asparaginase, polymeric micelles of paclitaxel have been recmended for various types of cancer treatment .The advancement of nano therapeutics and diagnostics can provide the improved effectiveness of the drug with less or no toxicity concerns. Similarly, diagnostic imaging is having potential future applications with newer imaging elements at nano level. The newly emerging field of nanorobotics can provide new directions in the field of healthcare. In this article, an attempt has been made to highlight the novel nanotherapeutic potentialities of polymeric nanoparticles, nanoemulsion, solid lipid nanoparticle, nanostructured lipid carriers, dendrimers, nanocapsules and nanosponges based approaches. The useful applications of these nano-medicines in the field of cancer, nutrition, and health have been discussed in details. Regulatory and safety concerns along with the commercial status of nanosystems have also been presented. In summary, a successful translation of emerging nanotherapeutics into commercial products may lead to an expansion of biomedical science. Towards the end of the review, future perspectives of this important field have been introduced briefly. PMID- 29793317 TI - Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms. AB - BACKGROUND: Metformin, a commonly used oral antidiabetic agent, is known to possess pleiotropic antioxidant, anti-inflammatory and anti-fibrotic effects. In this study, we evaluated the effect of metformin on pulmonary fibrosis and the mechanism underlying its effect. METHODS: Pulmonary fibrosis was induced experimentally with bleomycin (0.035 U/g, i.p.) given twice weekly for four weeks. Metformin (125, 250 and 500 mg/kg/day, p.o) was given seven days prior to first injection of bleomycin and continued till 28 days after starting bleomycin injection. Prednisolone (5 mg/kg/day, p.o) was the standard control. RESULTS: Administration of bleomycin caused pulmonary fibrosis in rats as evidenced by characteristic structural changes in histopathology, increased inflammatory cells in bronchoalveolar lavage fluid, elevated lipid peroxidation marker, depleted endogenous antioxidants and increased inflammatory mediators (TNF-alpha, IL-6). There were also increased levels of TGF-beta, Smad2/3, ERK1/2, p38, JNK, fibronectin, hydroxyproline and type I collagen in bleomycin-control group. All these changes were ameliorated by high dose metformin. It restored structural, biochemical and molecular changes towards normal. This protective effect may be attributed to activation of AMPK by metformin, with consequent reduction in oxidative stress and TGF-beta. Moreover, this protective effect was superior to prednisolone as metformin had additional antioxidant and antifibrotic properties. CONCLUSION: These data suggest that metformin protects against bleomycin-induced pulmonary fibrosis through activation of AMPK and amelioration of TGF-beta signaling pathways. PMID- 29793316 TI - Curcumin suppresses JNK pathway to attenuate BPA-induced insulin resistance in LO2 cells. AB - OBJECTIVE: To examine whether curcumin has protective effect on insulin resistance induced by bisphenol A (BPA) in LO2 cells and whether this effect was mediated by inhibiting the inflammatory mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) pathways. METHODS: LO2 cells were stimulated with BPA in the presence or absence of curcumin for 5 days. Glucose consumption, activation of insulin signaling, MAPKs and NF-kappaB pathways, levels of inflammatory cytokines and MDA production were analyzed. RESULTS: Curcumin prevented BPA-induced reduction of glucose consumption and suppression of insulin signaling pathway, indicating curcumin alleviated BPA-triggered insulin resistance in LO2 cells. mRNA and proteins levels of TNF-alpha and IL-6, as well as MDA level in LO2 cells treated with BPA were decreased by curcumin. Furthermore, curcumin downregulated the activation of p38, JNK, and NF-kappaB pathways upon stimulation with BPA. Inhibition of JNK pathway, but not p38 nor NF kappaB pathway, improved glucose consumption and insulin signaling in BPA-treated LO2 cells. CONCLUSION: Curcumin inhibits BPA-induced insulin resistance by suppressing JNK pathway. PMID- 29793319 TI - Oroxyloside inhibits human glioma progression by suppressing proliferation, metastasis and inducing apoptosis related pathways. AB - Malignant glioma are linked to a high mortality rate. Therefore, it is necessary to explore and develop effective therapeutic strategy. Oroxyloside is a metabolite of oroxylin A. However, its inhibitory effects on cancer are little to be known. In the present study, we investigated the effects of oroxyloside on cell proliferation, migration, and apoptosis in vitro and in vivo in human glioma. The results indicated that oroxyloside significantly suppressed the proliferation of human glioma cells through inducing cell cycle arrest at G0/G1 phase through reducing Cyclin D1 and cyclin-dependent kinase 2 (CDK2) while enhancing p53 and p21 expressions. In addition, the migration of glioma cells was dramatically inhibited by oroxyloside in a dose-dependent manner, which was related to its modulation on extracellular matrix (ECM), as evidenced by up regulated E-cadherin, and metastasis-associated protein 3 (MTA3), whereas down regulated N-cadherin, Vimentin, Twist, alpha-smooth muscle actin (alpha-SMA) and Syndecan-2. Furthermore, oroxyloside treatment markedly induced apoptosis in glioma cells through improving Caspase-9, Caspase-3 and PARP cleavage, accompanied with high release of cytochrome c (Cyto-c) into cytoplasm and subsequently increase of apoptotic protease-activating factor 1 (Apaf-1). In vivo, oroxyloside administration significantly inhibited the glioma cell xenograft tumorigenesis through various signaling pathways, including suppression of Cyclin D1/CDK2 and ECM pathways, as well as potentiation of p53/p21 and Caspases pathways. Together, the findings above illustrated that oroxyloside, for the first time, was used as a promising candidate against human glioma. PMID- 29793318 TI - Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1. AB - BACKGROUND: Glioma is the most common cause of cancer-related death. Therapy based on radiation seemed to effectively, while the radioresistance of several glioblastoma cells abolished the therapy. Thus, to employ the potential mechanism underlying the radioresistance is essential for glioma treatment. METHODS: Radioresistant cells were constructed using the X-ray radiation. Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide (PI), respectively. Real-time PCR and western blot were performed to determine gene expression. Luciferase reporter assay was carried out to detect the relationship between miR-183 and LRIG1. Mice xenotransplant model of glioma was established to detect the role of miR-183 in vivo. RESULTS: The expression of miR-183 was increased, while LRIG1 was decreased in resistant tissues rather than in sensitive tissues. The expression of LRIG1 was lower in radioresistant gliblastoma cell line U251R rather than in normal glioblastoma cell line U251. Overexpressed miR-183 suppressed cell apoptosis in radioresistance U251R cells (U251R). MiR-183 targets LRIG1 to regulate its expression. U251R cells transfected miR-183 inhibitor promoted the expression of LRIG1, and decreased the expression of EFGR and p-Akt, while U251R cells co-transfected with shRNA-LRIG1 abolished the effects of miR-183 knockdown. U251 cells transfected with miR-183 mimic decreased the expression of LRIG1, and promoted the expression of EFGR and p-Akt, while cells co-transfected with pcDNA-LRIG1 abolished the effects of miR 183 overexpression. In vivo experiments demonstrated that miR-183 inhibitor suppressed tumor growth, while miR-183 mimic promoted tumor growth. CONCLUSION: MiR-183 overexpression promoted radioresistance of glioblastoma via down regulating LRIG1 and increasing the activity of EFGR/Akt. PMID- 29793321 TI - Micro RNA-518 inhibits gastric cancer cell growth by inducing apoptosis via targeting MDM2. AB - Gastric cancer is a most common malignancy and the third leading cause of cancer mortality worldwide. So it is important to identify the prognostic markers and effective therapeutic targets against gastric cancer. miRNA plays an important role in tumor cell cycle, differentiation, apoptosis, invasion and metastasis. Many studies devote to the mechanism of miRNA regulates gastric cancer carcinoma and progression. In the present study, we found that the level of miR-518 in gastric cancer and cell lines were lower than the control or the adjacent tissues by qRT-PCR. Transfected with miR-518 mimic trigger apoptosis in MKN45 and HGC27 gastric cancer cell in vitro and in vivo. Moreover, we found that MDM2 was negatively regulated by miR-518 via targeting 26-32 site of 3'UTR using luciferase reporter assay. The western blot assay showed that miR-518 up regulated the expression of p53, pro-apoptotic protein Bax and active the activity of cleaved caspase-3, down-regulated expression of anti-apoptotic protein Bcl-2 via targeting MDM2. Thus, our study suggested that miR-518 acted as a new tumor suppressor by targeting MDM2 gene and trigger apoptosis in vivo and in vitro. The findings of the study first established the role of miR-518 in gastric cancer and may be a potential therapeutic target against gastric cancer in the further. PMID- 29793322 TI - Evaluation of Aristolochia indica L. and Piper nigrum L. methanol extract against centipede Scolopendra moristans L. using Wistar albino rats and screening of bioactive compounds by high pressure liquid chromatography: a polyherbal formulation. AB - The present study was aimed to explore the anti-venom activity of Aristolochia indica and Piper nigrum plants against the centipede (Scolopendra moristans) envenomation in animal model. In vtiro phytochemical, antioxidant and blocking of proteolysis were carried out by using standard spectrophotometric methods. In vivo anti-venom activity of methanol extracts was determined using Wistar albino rats after fixing lethal and effective doses. The electrolytes, lipid, liver, kidney, hematological parameters were analyzed and histopathology of skin and liver were also examined. Anti-skin cancer by MTT method and HPLC analysis were also carried out. The CAIPN extract showed higher total phenolics (150.65 +/- 0.08 mg GAE/g extract) and flavonoids (158.97 +/- 0.93 mg RE/g extract) content. Further, the same extract revealed the higher molybdenum reducing, inhibition of lipid peroxidation (80.08 +/- 0.22%), DPPH radical scavenging (3.05 MUg/mL), and blocking of proteolysis activities (96.45 +/- 0.04%). The parameters like hypersensitivity, electrolytes, lipids, blood components, liver and kidney marker of the CAIPN methanol extract (200 mg/kg) treated envenomated rats was remarkable and same as in the normal animals. Such status was also achieved by RBAI and SPN at 600 mg/kg. The histopathological scoring of skin and liver confirmed the venom neutralizing activity of CAIPN. Also, the CAIPN methanol extract was notable in anti-skin cancer activity (208 MUg/mL). The presence of the ferulic acid (04 +/- 0.09 MUg/mg) and quercetin (35.30 +/- 0.30 MUg/mg) like compounds was confirmed by HPLC analysis. Hence, the present investigation results conclude that the CAIPN was significant in their action and this polyherbal formulation could be considered as a new source for the pharmaceutical industries to develop a new effective, ecofriendly anti-venom drug. PMID- 29793320 TI - Orofacial antinociceptive effect of Mimosa tenuiflora (Willd.) Poiret. AB - Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles. PMID- 29793323 TI - Selective effects of Euterpe oleracea (acai) on Leishmania (Leishmania) amazonensis and Leishmania infantum. AB - Leishmania (Leishmania) amazonensis and Leishmania infantum (=Leishmania chagasi) are protozoa that cause American cutaneous and visceral leishmaniasis, respectively. These diseases show a high incidence in developing countries such as Brazil. The treatments used for leishmaniasis are still limited due to their high cost and toxicity. Currently, some natural products are considered an important alternative source of new leishmanicidal agents. Euterpe oleracea Martius, a palm producing black fruits, is frequently consumed in the Amazon region, as a juice, known as acai, with potent antioxidant, anti-inflammatory and anticonvulsant properties. Interestingly, the biological activity of clarified acai juice (EO) on L. (L.) amazonensis and L. infantum (=L. chagasi) is unknown. Therefore, the mechanism of anti-leishmanial action of EO has been evaluated on L. (L.) amazonensis and L. infantum (=L. chagasi). EO reduced the number of promastigotes and caused morphological alterations, increased the production of reactive oxygen species (ROS) and induced cell death phenotypes probably seems by apoptosis in the promastigotes of L. (L.) amazonensis (IC50 = 1:40) and L. infantum (=L. chagasi) (IC50 = 1:38). EO also presented activity against Leishmania amastigotes. Treatment with EO for 72 h strongly reduced IL-17 cytokine levels at all tested concentrations and decreased the number of intracellular amastigotes in macrophages infected with L. (L.) amazonensis (IC50 = 1:30) and L. infantum (=L. chagasi) (IC50 = 1:38). Additionally, no cytotoxic effect was observed in murine macrophages treated with EO (72 h - CC50 > 1:1). Our results demonstrated that EO has leishmanicidal activity against two different species that cause American visceral and cutaneous leishmaniasis without cytotoxic effects for the host cell. PMID- 29793324 TI - Evaluation of the antithrombotic activity of Zhi-Xiong Capsules, a Traditional Chinese Medicinal formula, via the pathway of anti-coagulation, anti-platelet activation and anti-fibrinolysis. AB - Zhi-Xiong Capsules (ZXC) involving Hirudo, Ligusticum chuanxiong, Salvia miltiorrhiza, Leonurus artemisia, and Pueraria lobata, is an empirical prescription used in Chinese clinics applied for treating cerebral arteriosclerosis and blood-stasis in clinic. However, the mechanism of its antithrombotic activity has not been investigated until now. The present study was designed to investigate its antithrombotic effects, the mechanism of ZXC on anti-thrombus action and to identify the main chemical composition of ZXC using HPLC-DAD-ESI-IT-TOF-MS. Two animal models were used to evaluate the antithrombotic effect of ZXC, the arterial thrombosis model and a venous thrombosis model. ZXC prolonged the plasma recalcification time (PRT), the activated partial thromboplastin time (APTT), the thrombin time (TT) and the prothrombin time (PT) and clearly reduced the content of fibrinogen (FIB) obviously in the arterial thrombosis model. Furthermore, it markedly suppressed the level of TXB2 and up-regulated the level of 6-keto-PGF1a. In addition, it significantly up-regulated the level of t-PA and down-regulated the level of PAI 1 (p < 0.05). These results revealed that ZXC played a vital role in the prevention of thrombosis through interacting with multiple targets, including inhibition of coagulation and platelet aggregation and increasing thrombolysis. A total of 23 compounds were identified as the main components of ZXC by HPLC-DAD ESI-IT TOF-MS. PMID- 29793325 TI - NY-SAR-35 is involved in apoptosis, cell migration, invasion and epithelial to mesenchymal transition in glioma. AB - Glioma is one of the most adult intracranial tumors worldwide. Cancer testis antigens have been confirmed as new tool for immunotherapy and prognostic biomarkers in a variety of neoplasms. NY-SAR-35 has emerged to be upregulated in diverse human carcinomas. In this study, we aimed to investigate the role of NY SAR-35 of clinical significance in glioma and investigate whether NY-SAR-35 correlate with malignant behaviors of glioma cells, including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). As the results showed, NY-SAR-35 was significantly upregulated in glioma clinical samples and cell lines, and the high expression was significantly associate with age (p = 0.05), the WHO classification (p = 0.02) and KPS score (p = 0.016). Therefore, NY-SAR-35 could serve as an independent prognostic biomarker of glioma patients. Moreover, increased NY-SAR-35 expression remarkably accelerated tumor cells proliferation, restrained cells apoptosis, promoted cells metastasis and contributed to the formation of EMT phenotype. Likewise, down-regulated NY-SAR-35 could obviously inhibit cells proliferation, promote cells apoptosis, supressed metastasis and reverse EMT to MET. In summary, our findings showed that NY-SAR-35 serves as a novel prognostic biomarker and therapeutic target for glioma. PMID- 29793326 TI - Procyanidins extracted from the litchi pericarp attenuate atherosclerosis and hyperlipidemia associated with consumption of a high fat diet in apolipoprotein-E knockout mice. AB - The beneficial effects of red wine against cardiovascular disease are associated with the abundant antioxidant polyphenols such as procyanidins. Recently, procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins showed strong antioxidant activities in vitro, have been isolated and identified in our laboratory. The aim of present study was to investigate the anti-atherosclerotic effects of LPPC on atherosclerosis and hyperlipidemia in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet (HFD, 21% fat, 0.15% cholesterol) for 24 weeks. The results showed that LPPC intervention alleviated atherosclerosis, fat accumulation and hyperlipidemia in ApoE KO mice. Furthermore, real-time RT-PCR results showed that LPPC can regulate several key genes involved in hepatic lipid homeostasis, such as increasing mRNA levels of farnesoid X receptor (FXR) and small heterodimer partner (SHP) which emerge as key regulators of lipid homeostasis at the transcriptional level, decreasing mRNA levels of 3-hydroxy-3-Methylglutaryl (HMG)-CoA reductase which mediates cholestrol biosynthesis, and up-regulating the mRNA expressions of ATP-binding cassette transporter-1 (ABCA1) which modulates cholesterol efflux. Thus, these results elucidated that LPPC could alleviate the lipid disorder especially hypercholesteromia and ameliorate atherosclerosis in ApoE-KO mice fed a WTD via regulating gene expression involved in hepatic lipid homeostasis effectively. PMID- 29793327 TI - LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis. AB - BACKGROUND: LncRNA taurine upregulated gene 1 (TUG1) was reported to act as a possible oncogene in osteosarcoma (OS) development. However, the underlying molecular basis of TUG1 involved in the progression of OS remains to be thoroughly investigated. METHODS: The expressions of TUG1 and miR-212-3p in OS tissues and cells were examined by RT-qPCR. Cell proliferation, apoptosis, caspase-3 activity, protein levels of BCL2, Bax, and forkhead box A1 (FOXA1) were detected by colony formation assay, MTT assay, flow cytometry analysis, caspase-3 activity assay, and western blot. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RT-qPCR were used to explore the interaction between TUG1, FOXA1 and miR-212-3p. Tumor xenograft mouse model was used to confirm the biological role of TUG in OS in vivo. RESULTS: Elevated TUG1 and FOXA1 expression and reduced miR-212-3p expression were observed in OS tissues and cells. TUG1 knockdown suppressed OS cell proliferation and promoted apoptosis. TUG1 functioned as a ceRNA of miR-212-3p and suppressed miR-212-3p expression. miR-212-3p inhibition reversed the effect of TUG1 knockdown on OS cell proliferation and apoptosis. In addition, FOXA1 was identified as a target of miR-212-3p and TUG1 functioned as a ceRNA to upregulate FOXA1 by sponging miR 212-3p in OS cells. FOXA1 up-regulation abolished the effects of miR-212-3p on OS cell proliferation and apoptosis. CONCLUSION: TUG1 promoted OS cell proliferation and suppressed apoptosis by regulating the miR-212-3p/FOXA1 axis. Therefore, TUG1/miR-212-3p/FOXA1 axis may be a promising therapeutic target in OS treatment. PMID- 29793328 TI - Rosa damascena restrains Plasmodium falciparum progression in vitro and impedes malaria pathogenesis in murine model. AB - Malaria the parasitic disease of tropical countries is seeking newer therapeutic strategies owing to the drug resistance to existing drugs. The pathogenesis after infection renders the host to oxidative stress resulting in an altered immune status. Natural products rich in phenols are a source of bio-actives that could have a role in alleviating such condition. The present study reports the phenol rich ethyl acetate extract from the petals of Rosa damascena (RdEa) to be active against Plasmodium falciparum in-vitro and Plasmodium berghei in-vivo. It restores the haemoglobin level while increasing the mean survival time and chemo suppression in P. berghei infected mice. The HPLC characterised RdEa was found to be rich in Gallic acid and Rutin besides other phenols. RdEa was capable of scavenging the free radicals and modulating the pro-inflammatory mediators (IL6, TNF, IFN and NO) favourably and also restored the architecture of hepatocytes as evidenced through histopathology. The extract was able to arrest the lipopolysaccharide (LPS) induced damage of J774A.1 cells (murine macrophages) and was found to be safe in mice upto 2000 mg/kg body weight. PMID- 29793329 TI - FGF21 and DPP-4 inhibitor equally prevents cognitive decline in obese rats. AB - The beneficial effects of Fibroblast Growth Factor 21 (FGF21) on metabolic function and neuroprotection have been shown in earlier research. We have previously shown that the Dipeptidyl Peptidase 4 inhibitor, vildagliptin, also led to improved insulin sensitivity and brain function in the obese-insulin resistant condition. However, the comparative efficacy on the improvement of metabolic function and neuroprotection between FGF21 and vildagliptin in the obese-insulin resistant condition has never been investigated. Twenty-four male Wistar rats were divided into two groups, and received either a normal diet (ND, n=6) or a high fat diet (HFD, n=18) for 16 weeks. At week 13, the HFD-fed rats were divided into three subgroups (n=6/subgroup) to receive either a vehicle, recombinant human FGF21 (0.1mg/kg/day) or vildagliptin (3mg/kg/day), for four weeks. ND-fed rats were given a vehicle for four weeks. The metabolic parameters and brain function were subsequently investigated. The results demonstrated that the rats fed on HFD had obese-insulin resistance, increased systemic inflammation, brain mitochondrial dysfunction, increased brain apoptosis, impaired hippocampal plasticity, and demonstrated cognitive decline. FGF21 and vildagliptin effectively attenuated peripheral insulin resistance, brain mitochondrial dysfunction, brain apoptosis and cognitive decline. However, only FGF21 treatment led to significantly reduced body weight gain, visceral fat, systemic inflammation, improved hippocampal synaptic plasticity, enhanced FGF21 mediated signaling in the brain leading to prevention of early cognitive decline. These findings suggest that FGF21 exerts greater efficacy than vildagliptin in restoring metabolic function as well as brain function in cases of obese-insulin resistant rats. PMID- 29793330 TI - Baicalin alleviates atherosclerosis by relieving oxidative stress and inflammatory responses via inactivating the NF-kappaB and p38 MAPK signaling pathways. AB - Atherosclerosis (AS) is a chronic progressive disease related to inflammatory reaction. Baicalin is a flavonoid isolated from Scutellaria baicalensis georgi (Huang-qin) and exerts anti-inflammation effects in various diseases. Here, we investigated the protective effects of baicalin treatment and the potential mechanism in AS progression on AS mouse model. After ApoE-/- mice with high-lipid diets had received 12 weeks' of baicalin treatment at different concentrations, plasma lipids levels and atherosclerotic plaque areas in aorta were measured and there exhibited a prominent improvement in the baicalin treated mice compared with mice in AS model group. The expression of lipolysis related proteins (PPARalpha, CPT-1) was increased while the expression of adipogenesis related proteins (SREBP-1c, ACS) was decreased by baicalin treatment, indicating the anti adipogenic effect of baicalin. Moreover, baicalin up-regulated the activities of antioxidant enzymes (SOD, CAT and GSH-Px) and down-regulated the activity of oxidative parameter MDA compared with AS model group, indicating the anti-oxidant effect of baicalin. The increased levels of pro-inflammatory cytokines (IL-6, TNF alpha, sVE-cadherin) induced by AS were also decreased by baicalin treatment, indicating that baicalin acted as an anti-inflammation regulator in AS. In addition, we further explored the potential mechanism of baicalin treatment on AS, and found that baicalin treatment attenuated the high phosphorylation levels of JNK, p65, p-38 and ERK1/2 induced by AS, indicating that baicalin treatment inhibited the NF-kappaB and p38 MAPK signaling pathways in AS. In conclusion, baicalin treatment inhibited the NF-kappaB and p38 MAPK signaling pathways, thereby achieved its anti-adipogenic effect, anti-oxidant effect and anti inflammation effect in a dose-dependent manner in AS. PMID- 29793331 TI - Ameliorative effects of fruit stem extract from Muscat Bailey A against chronic UV-induced skin damage in BALB/c mice. AB - This study analyzed fruit stem extract (MGFE) from Muscat Bailey A grape (Vitis labrusca * Vitis vinifera) for their ameliorative effects on Ultraviolet B (UVB) induced skin damage in Balb/c mice. Well established in vivo assays were used to determine the biological effects of MGFE upon UVB irradiation of BALB/c mice. The results showed that treatment with MGFE recovered glutathione depletion, prevented lipid peroxidation of tissues and decreased the expression of DNA repair enzyme oxo guanine glycosylase-1. MGFE recovered the skin conditions in UVB-irradiated Balb/c mice. Moreover, MGFE inhibited dermal infiltration of inflammatory cells and reduced serum tumor necrosis factor alpha and interleukin 6 levels. Finally, MGFE treatment inhibited UVB-induced melanin formation and collagen fiber destruction through the inhibition of matrix metalloproteinase-1 expression. Through high-performance liquid chromatography analysis, catechin, epicatechin, and trans-resveratrol were found to be among the main active compounds present in MGFE. Taken together, these results indicated that MGFE has potentials as topical therapeutic materials against skin damage by inhibiting oxidative stress and inflammatory. PMID- 29793333 TI - Oleanolic acid protects against pathogenesis of atherosclerosis, possibly via FXR mediated angiotensin (Ang)-(1-7) upregulation. AB - Atherosclerosis, the leading cause of cardiovascular diseases in the world, is a chronic inflammatory disorder characterized by the dysfunction of arteries. Oleanolic acid (OA) is a bioactive nature product which exists in various plants and herbs. Previous studies have demonstrated that OA was involved in numerous of biological processes, including atherosclerosis. However, the exact mechanisms of the anti-atherosclerosis effects of OA remain unknown. Here, in our study, we analyzed the effects and possible underlying mechanisms of OA in atherosclerosis depending a cell model and an animal model of atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL, 100 MUg/mL) for 24 h to establish an atherosclerotic cell model. New Zealand white (NZW) rabbits were fed with high-fat (HF) diets for three months to establish an atherosclerotic animal model. Then, cell viability and expression of cytokines (ANG, NO, eNOS, IL-1beta, TNF-alpha, and IL-6) were measured with CCK-8 assay and ELISA kits, cell apoptosis and cell cycle distribution were analyzed by flow cytometry in the atherosclerotic cell model. Results showed that ox-LDL induced effects of anti-proliferation, cytokines alterations, and cell apoptosis were abolished by the application of OA or Ang (1 7). Further study indicated that OA increased the expression of ANG by upregulating the FXR expression in the ox-LDL induced HUVECs arthrosclerosis model. And the in vivo experiment in the HF diet induced animal model suggested that OA may inhibit the development of atherosclerosis. The atherosclerosis of aortas was assessed by Hematoxylin Eosin (HE), Oil Red O and Picrosirius Red staining; the expression levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were determined by the fully automatic biochemical analyzer, in the atherosclerotic animal model. All the results showed that OA treatment improved the cell viability in the cell model, inhibited the atherosclerosis development in the animal model. OA play as an anti-atherosclerosis agent in both the cell model and animal model by upregulating the production of Angiotensin (Ang)-(1-7) through FXR. PMID- 29793332 TI - Effects of penehyclidine hydrochloride on severe acute pancreatitis-associated acute lung injury in rats. AB - Penehyclidine hydrochloride (PHC) is a selective M1 and M3 receptor antagonist. This study was designed to investigate the effect of PHC on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) and the expression of hypoxia inducible factor-1alpha (HIF-1alpha) in rats. A total of 45 healthy adult male SD rats were randomly divided into 3 groups: an S group, sham operation; an ALI group, pancreatitis-associated acute lung injury (PALI); and a P group, PALI treated with PHC. Rats from the ALI and P groups were used to establish a model of acute lung injury associated with SAP by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Rats in the P group, reflecting acute lung injury caused by SAP, were treated with PHC immediately following SAP. Rats in the S and ALI groups were injected with the same amount of 0.9% sodium chloride solution. After modeling, the rats were sacrificed at 12h. The wet/dry weight (W/D) ratios of lung tissue were calculated. Pathological changes in pancreatic and lung tissues were scored. The expression levels of TLR4 and NF kappaB p65 in lung tissue were detected by Western blot. RT-PCR was used to detect HIF-1alpha mRNA in lung tissue. The HIF-1alpha, IL-1beta, and IL-6 expression levels in lung tissues and serum amylase levels were detected by ELISA. The results showed extensive infiltration of neutrophils, alveolar hemorrhage and necrosis and fat necrosis in the pancreatic tissue of rats in the PALI and P groups. Their pancreatic tissue injury scores were significantly higher than the score of the S group (P<0.01). However, no statistically significant difference was observed in the serum amylase levels of the P and ALI groups (P>0.05). The W/D ratios of lung tissue in the ALI and P group rats were significantly higher than those in the S group (P<0.05). Compared with those of the ALI group rats, the lung tissue pathological changes of the P group were significantly improved, and the lung W/D value was significantly lower than that of the ALI group (P<0.05). Compared with those of the S group, the TLR4, NF kappaB p65, HIF-1alpha mRNA, and HIF-1alpha expression levels in the lung tissue of the ALI and P groups were significantly higher (P<0.01), and the TLR4, NF kappaB p65, HIF-1alpha mRNA, HIF-1alpha, IL-1beta and IL-6 expression levels in the P group were significantly lower than those in the ALI group (P<0.05). The current work indicates that PHC could not alleviate the damage to pancreatic tissue caused by SAP. However, PHC did suppress HIF-1alpha, IL-1beta and IL-6 expression levels and reduced the acute lung injury induced by SAP in rats, which might depend on suppression of the expression of inflammatory factors, such as HIF-1alpha. PMID- 29793334 TI - The C and E subunits of the serotonin 5-HT3 receptor subtly modulate electrical properties of the receptor. AB - Serotonin type 3 (5-hydroxytrptamine-3, 5-HT3) receptors are ligand-gated cation channels present in both central and peripheral nervous systems. In humans there are five different subunits (A, B, C, D and E) of 5-HT3 receptors which can form homomeric or heteromeric receptors that may account for discrepancies in patient responses to treatments. The present study commences characterisation of the profiles of human 5-HT3 receptors containing C and/or E subunits. Recombinant 5 HT3 receptors were expressed transiently in HEK293T cells and expression was checked via immunocytochemistry staining against each epitope-tagged subunits. Functional characterisation of different combinations of 5-HT3 receptor complexes was studied via patch clamp whole cell recordings. In this study, increased current was seen in cells containing A and C subunits but only subtle changes were seen in the electrical properties of cells expressing A, AE, or ACE subunits in response to the ligand, 5-HT. Both di- and tri-heteromeric 5-HT3 receptors were significantly inhibited by the antagonists, ondansetron and palonosetron. Notably, palonosetron exerted stronger and more rapid inhibition on the 5-HT3 receptor ACE tri-heteromer compared to homomeric and di-heteromeric counterparts. This study demonstrated that the C and E subunits when assembled as simple or complex heteromeric 5-HT3 receptors may alter efficacies of 5-HT and clinically used antagonists such as ondansetron and palonosetron, and this in turn may have implications for patient responses to therapies. PMID- 29793336 TI - Computational Investigation of the Effect of Backbone Chiral Inversions on Polypeptide Structure. AB - Studying a set of helix-folding polyalanine peptides with systematically inserted chiral inversions in explicit water, we investigate quantitatively the effect of chiral perturbations on the structural ensembles of the peptides, thereby assessing the extent to which the backbone structure is able to fold in the presence of systematic heterochiral perturbations. Starting from the homochiral l Ala20 peptide, we invert the backbone chiralities of Ala residues one by one along a specific perturbation pathway, until reaching the homochiral d-Ala20 peptide. Analysis of the helical contents of the simulated structural ensembles of the peptides shows that even a single inversion in the middle of the peptide completely breaks the helical structure in its vicinity and drastically reduces the helical content of the peptide. Further inversions in the middle of the peptide monotonically decrease the original helical content, that is, the right handed helical content for l-Ala, and increase the helical content of the opposite chirality. Further analysis of the peptide ensembles using several size- and shape-related order parameters also indicate the drastic global changes in the peptide structure due to the local effects caused by the chiral inversions, such as formation of a reverse turn. However, the degree of the structural changes introduced by opposite chirality substitutions depends on the position of the inversion. PMID- 29793335 TI - Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. AB - Ziziphora clinopodioides has been used in traditional medicine for its anti inflammatory properties. Current study is believed to first time report the potential of Z. clinopodioides extracts to ameliorate joint inflammation using model of chronic joint inflammation (FCA-induced rheumatoid arthritis). The study further investigates the effects on joint inflammation using acute inflammatory paw edema models. The anti-inflammatory effects were also supported by using xylene-induced ear edema model. Results showed that Z. clinopodioides significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic development and paw edema. Histopathological examination showed significant attenuation in pannus formation, bone erosion, and joint inflammation. Treatment with the plant extracts also nearly normalized counts of RBCs, platelets, and total leukocytes along with hemoglobin (Hb) content. Biochemical analysis (AST, ALT, urea, and creatinine) showed that plant extracts did not possess hepatotoxic or nephrotoxic effects. Water displacement plethysmometric analysis showed that Z. clinopodioides significantly attenuated carrageenan-induced paw edema. To evaluate the mechanism, anti-inflammatory effects were further evaluated using histamine- and serotonin-induced inflammatory paw edema models. Z. clinopodioides significantly suppressed paw edema induced by both histamine and serotonin, and also caused the inhibition of xylene-induced ear edema. This suggested the inhibition of autacoids as one of the mechanisms of anti-inflammatory effects of plant. GC-MS analysis showed that the plant is rich in essential oils, including terpenoids, esters, alcohols, furans, cyclic ketones, epoxides, oxanes, and acyclic hydrocarbons. In conclusion, current study demonstrated that Z. clinopodioides possessed significant anti-arthritic and anti-inflammatory properties which might be attributed to the inhibition of autacoids. PMID- 29793337 TI - Thermosensitive Lipid Bilayer-Coated Mesoporous Carbon Nanoparticles for Synergistic Thermochemotherapy of Tumor. AB - Thermochemotherapy exhibits a synergistic therapeutic efficiency for cancer, and the sensitivity of cancer cells to chemical drugs could be increased to a large extent at elevated temperature. In this work, a biocompatible nanocomposite thermosensitive mesoporous carbon nanoparticles (TSMCN) was prepared by covering a liposome on mesoporous carbon nanoparticles (MCN). The TSMCN had good photothermal efficiency and photostability. The doxorubicin (DOX)-loaded TSMCN (DOX/TSMCN) showed a slower release than the DOX-loaded MCN-COOH (DOX/MCN-COOH) both in simulated tumor environment and physiological environment. And release curves of DOX/TSMCN exposed to NIR laser exhibited the fast release property. The confocal laser scanning microscopy results illustrated that cellular uptake of DOX for DOX/TSMCN can be enhanced by NIR laser. The temperature of the tumor site reached up to 51.9 degrees C within 3 min after exposure to laser at 1.25 W/cm2 power density, which is above the phase transition temperature ( Tm) of liposome (40.7 degrees C). The biodistribution of DOX in vivo indicated that NIR laser can prolong the retardation time of DOX in the tumor site. The results of both 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and antitumor efficiency elucidated that the DOX/TSMCN under NIR irradiation had a synergistic therapeutic effect for cancer. Thus, the TSMCN could be explored as a powerful nanoplatform that shows great prospect in thermochemotherapy of tumor therapy. PMID- 29793338 TI - Presence of Short Intermolecular Contacts Screens for Kinetic Stability in Packing Polymorphs. AB - Polymorphism is pervasive in molecular solids. While computational predictions of the molecular polymorphic landscape have improved significantly, identifying which polymorphs are preferentially accessed and experimentally stable remains a challenge. We report a framework that correlates short intermolecular contacts with polymorphic stability. The presence of short contacts between neighboring molecules prevents structural rearrangement and stabilizes the packing arrangement, even when the stabilized polymorph is not enthalpically favored. In the absence of such intermolecular short contacts, the molecules have added degrees of freedom for structural rearrangement, and solid-solid polymorphic transformations occur readily. Starting with a series of core-halogenated naphthalene tetracarboxylic diimides, we establish this framework with the packing polymorphs of more than 20 compounds, ranging from molecular semiconductors to pharmaceutics and biological building blocks. This framework, widely applicable across molecular solids, can help refine computational predictions by identifying the polymorphs that are kinetically stable. PMID- 29793339 TI - Quercitol: From a Taxonomic Marker of the Genus Quercus to a Versatile Chiral Building Block of Antidiabetic Agents. AB - Quercitol is a cyclohexanepentol that has been recognized as a biomarker of plants in genus Quercus, which includes oak. As a result of its glucose-like structure, it has been introduced as an alternative chiral building block in the synthesis of several bioactive compounds. Our continuing investigations on the synthesis of antidiabetic agents from quercitol have demonstrated that this chiral synthon can generate diverse structural features with improved hypoglycemic activity. PMID- 29793340 TI - Identification of MS-Cleavable and Noncleavable Chemically Cross-Linked Peptides with MetaMorpheus. AB - Protein chemical cross-linking combined with mass spectrometry has become an important technique for the analysis of protein structure and protein-protein interactions. A variety of cross-linkers are well developed, but reliable, rapid, and user-friendly tools for large-scale analysis of cross-linked proteins are still in need. Here we report MetaMorpheusXL, a new search module within the MetaMorpheus software suite that identifies both MS-cleavable and noncleavable cross-linked peptides in MS data. MetaMorpheusXL identifies MS-cleavable cross linked peptides with an ion-indexing algorithm, which enables an efficient large database search. The identification does not require the presence of signature fragment ions, an advantage compared with similar programs such as XlinkX. One complication associated with the need for signature ions from cleavable cross linkers such as DSSO (disuccinimidyl sulfoxide) is the requirement for multiple fragmentation types and energy combinations, which is not necessary for MetaMorpheusXL. The ability to perform proteome-wide analysis is another advantage of MetaMorpheusXL compared with programs such as MeroX and DXMSMS. MetaMorpheusXL is also faster than other currently available MS-cleavable cross link search software programs. It is imbedded in MetaMorpheus, an open-source and freely available software suite that provides a reliable, fast, user-friendly graphical user interface that is readily accessible to researchers. PMID- 29793341 TI - Exploring Molecular-Biomembrane Interactions with Surface Plasmon Resonance and Dual Polarization Interferometry Technology: Expanding the Spotlight onto Biomembrane Structure. AB - The molecular analysis of biomolecular-membrane interactions is central to understanding most cellular systems but has emerged as a complex technical challenge given the complexities of membrane structure and composition across all living cells. We present a review of the application of surface plasmon resonance and dual polarization interferometry-based biosensors to the study of biomembrane based systems using both planar mono- or bilayers or liposomes. We first describe the optical principals and instrumentation of surface plasmon resonance, including both linear and extraordinary transmission modes and dual polarization interferometry. We then describe the wide range of model membrane systems that have been developed for deposition on the chips surfaces that include planar, polymer cushioned, tethered bilayers, and liposomes. This is followed by a description of the different chemical immobilization or physisorption techniques. The application of this broad range of engineered membrane surfaces to biomolecular-membrane interactions is then overviewed and how the information obtained using these techniques enhance our molecular understanding of membrane mediated peptide and protein function. We first discuss experiments where SPR alone has been used to characterize membrane binding and describe how these studies yielded novel insight into the molecular events associated with membrane interactions and how they provided a significant impetus to more recent studies that focus on coincident membrane structure changes during binding of peptides and proteins. We then discuss the emerging limitations of not monitoring the effects on membrane structure and how SPR data can be combined with DPI to provide significant new information on how a membrane responds to the binding of peptides and proteins. PMID- 29793343 TI - ACS Sensors Hits the Road. PMID- 29793344 TI - Impact of a remotely delivered, writing for publication program on publication outcomes of novice researchers. AB - INTRODUCTION: Increased publication of clinician-led health research is important for improving patient care and health outcomes. The aim of this retrospective cohort study conducted in rural Australia was to determine the impact of a writing for publication (WFP) program delivered by teleconference on the publication rates and skill acquisition of novice researchers who have graduated from the New South Wales (NSW) Health Education and Training Institute Rural Research Capacity Building Program (RRCBP). METHODS: Between 2012 and 2015, eight WFP 'bootcamp' programs were offered by the New South Wales Health Education and Training Institute to 112 RRCBP graduates, resulting in 50 participants completing at least one bootcamp. Participants completed a once-weekly WFP group teleconference for six consecutive weeks, and were expected to complete homework activities between sessions and participate in two follow-up teleconferences within 3 months of program conclusion. The primary outcome measure was manuscript publication resulting from participation in bootcamp, with secondary measures being changes in skills, knowledge and confidence in WFP, publication rate and cost per publication. RESULTS: Twenty-one participants (42%) published their bootcamp paper or a related paper that directly resulted from bootcamp WFP skills. Five other participants submitted their bootcamp manuscript for publication, but had not yet had it accepted for publication. The overall publication rate of RRCBP graduates who completed bootcamp was 0.80 compared to 0.23 who did not complete bootcamp. On a 1 to 5 scale, mean scores increased for writing (knowledge, experience, confidence) from 2.0 to 3.5 (p<0.01) and for publishing from 1.1 to 3.4 (p<0.01). The estimated cost incurred by the RRCBP to deliver the program was $230 per publication. CONCLUSION: WFP workshops delivered by teleconference support rural clinician researchers to improve their skills in writing and publishing. A remotely conducted WFP program was effective in increasing publication rates among novice researchers who had conducted a clinically based research project. This shows that novice researchers respond to similar intervention features as experienced researchers do when engaging with WFP, and that WFP outcomes can be increased substantially with modest investment of funding and resources by the host organisation. PMID- 29793346 TI - Accurate Patient Selection for Percutaneous Coronary Intervention for Coronary Chronic Total Occlusions. PMID- 29793345 TI - Dignity Impact as a Primary Outcome Measure for Dignity Therapy. AB - BACKGROUND: Feasibility of dignity therapy (DT) is well established in palliative care. Evidence of its efficacy, however, has been inconsistent and may stem from DT's primary effects differing from the outcomes measured in previous studies. We proposed that DT effects were in the spiritual domain and created a new outcome measure, Dignity Impact Scale (DIS), from items previously used in a large randomized controlled trial (RCT). OBJECTIVE: The purpose of this secondary analysis study was to examine properties of a new measure of dignity impact. DESIGN: Using the DIS, we conducted reanalysis of posttest data from a large 3 arm, multi-site RCT study. SETTING/PARTICIPANTS: Participants were receiving hospice/palliative care (n = 326, 50.6% female, mean age = 65.1 years, 89.3% white, all with a terminal illness with 6 months or less life expectancy). They had been randomized to standard palliative care (n = 111), client-centered care (n = 107), or DT (n = 108). MEASUREMENT: The 7-item DIS was derived from selected items in a posttest DT Patient Feedback Questionnaire. The DIS had strong internal consistency (alpha = 0.85). RESULTS: The DT group mean DIS score (21.4 +/- 5.0) was significantly higher than the usual care group mean score (17.7 +/- 5.5; t = 5.2, df = 216, P < .001) and a client-centered intervention group mean score (17.9 +/- 4.9; t = 5.2, df = 213, P < .001). CONCLUSION: We found that, compared to both other groups, patients who received DT reported significantly higher DIS ratings, which is consistent with the DT focus on meaning-making, preparation for death, and life completion tasks. We propose that the DIS be used as the primary outcome measure in evaluating the effects of DT. PMID- 29793347 TI - Effect of beta-blocker Therapy on Hospital Readmission and Mortality in Heart Failure Patients With Concurrent Cocaine Use. AB - BACKGROUND: beta-Blockers are first-line agents for reduction in symptoms, hospitalization, and mortality in patients with heart failure having reduced ejection fraction (HFrEF). However, the safety and efficacy of continuous beta blocker therapy (BBT) in patients who actively use cocaine remain controversial, and available literature is limited. We aimed to evaluate the effect of BBT on hospital readmission and mortality in patients having HFrEF with concurrent cocaine use. METHODS: We conducted a retrospective study of patients with a diagnosis of HFrEF between 2011 and 2014 based on International Classification of Diseases 9-Clinical Modification codes. We included patients aged 18 and older who tested positive for cocaine on a urine toxicology test obtained at the time of index admission. Patients were followed for 1 year. Multivariate logistic regression was used to assess the effect of BBT on the 30-day, all-cause and heart failure-related readmissions. RESULTS: The 30-day readmission rates for BBT versus no BBT groups were 20% versus 41% (odds ratio [OR]: 0.17, 95% confidence interval [CI] = 0.05-0.56, P = .004) for heart failure-related readmissions and 25% versus 46% (OR: 0.19, 95% CI = 0.06-0.64, P = .007) for all-cause readmissions. CONCLUSION: The BBT reduced 30-day, all-cause and heart failure related readmission rate but not 1-year mortality in patients having HFrEF with concurrent cocaine use. PMID- 29793348 TI - Cooking loss, tenderness, and sensory evaluation of chicken meat roasted after wrapping with edible films. AB - In this study, edible films were produced from sodium caseinate and a sodium caseinate-starch mixture and with or without oleoresins (cumin and oregano oleoresin mixture). Chicken meat was wrapped in the respective films, stored at 4 C for four days, and roasted at 200 C for 30 min. The cooking loss, color changes, instrumental tenderness (shear force and energy) were measured. In addition, sensory evaluation was performed. All films effectively reduced cooking loss from chicken meat. The sodium caseinate-starch-based films were the most successful in preventing cooking loss. The average shear force and shear energy values of the wrapped samples were about 40% and 30% less than those of control samples, respectively. In sensory evaluation, chicken meat roasted after wrapping with the films was considered more tender and delicious than the control. Particularly, chicken meat wrapped with the films containing oleoresin mixture was assessed as the most delicious among the samples. It was shown that the cooking quality of the chicken meat could be significantly improved by pre wrapping the meat with edible films. PMID- 29793350 TI - Abuse Characteristics and the Concordance of Child Protective Service Determinations and Adolescent Self-Reports of Abuse. AB - This study examines the concordance of abuse self-reported by adolescents at 18 years and child protective service (CPS) determinations and how abuse characteristics predict concordance. It includes 819 youths participating in 18 year interviews of the Longitudinal Study of Child Abuse and Neglect (LONGSCAN). Cross-tabulations revealed low correspondence between self-reports and CPS determinations of physical, sexual, and emotional abuse. Logistic regression identified that among youths with CPS physical abuse determinations, White race, chronicity, and co-occurring neglect were positively associated with corresponding self-reports. Co-occurring CPS-determined emotional abuse was more concordant with self-reports. More frequent self-reported physical abuse was associated with corresponding CPS determinations. Self-reports of childhood emotional abuse and perpetration by nonparental family/other household members were positively associated with corresponding CPS determinations. CPS determination concordance also varied significantly by LONGSCAN site. Results demonstrate differences in abuse characteristics captured by CPS data and youth self-report, which may impact research findings on abuse correlates. PMID- 29793351 TI - Bacterial regulatory RNAs: complexity, function, and putative drug targeting. AB - Over the past decade, RNA-deep sequencing has uncovered copious non-protein coding RNAs (npcRNAs) in bacteria. Many of them are key players in the regulation of gene expression, taking part in various regulatory circuits, such as metabolic responses to different environmental stresses, virulence, antibiotic resistance, and host-pathogen interactions. This has contributed to the high adaptability of bacteria to changing or even hostile environments. Their mechanisms include the regulation of transcriptional termination, modulation of translation, and alteration of messenger RNA (mRNA) stability, as well as protein sequestration. Here, the mechanisms of gene expression by regulatory bacterial npcRNAs are comprehensively reviewed and supplemented with well-characterized examples. This class of molecules and their mechanisms of action might be useful targets for the development of novel antibiotics. PMID- 29793352 TI - Is there a role for minimally invasive thermal ablations in the treatment of autonomously functioning thyroid nodules? PMID- 29793353 TI - Developing, Planning and Conducting an Interim Analysis: Lessons From the DEVOTE Cardiovascular Outcomes Trial (Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events). AB - BACKGROUND: In 2013, a randomized, double-blind, active comparator-controlled, event-driven cardiovascular outcomes trial (DEVOTE) was initiated to compare the cardiovascular safety of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes at high risk of cardiovascular events. The FDA agreed that an interim analysis could form the basis for an early regulatory approval. We report here the operational model developed to support the DEVOTE interim analysis and the results. METHODS: The interim analysis model was designed to reduce the risk of any confidentiality breaches. The Data Access Management Plan comprehensively described the interim analysis operational processes and procedures to maintain the integrity of the ongoing trial while the interim analysis was conducted, submitted, and acted upon by the FDA, and also until completion of the full trial. Most importantly, those who were unblinded to the interim results were limited to a team of 14 members. RESULTS: A total of 150 first major adverse cardiovascular events were recorded at cut-off for the interim analysis. The estimated hazard ratio was 0.92 (95% CI 0.67, 1.27) and non-inferiority to glargine U100 was confirmed as the upper bound of the confidence interval was below 1.8, as prespecified. Based on these results, the FDA approved the use of degludec and degludec/insulin aspart (IDegAsp) in the United States in 2015 before trial completion. CONCLUSIONS: The DEVOTE interim analysis succeeded as a model by which to conduct an interim analysis and submit confidential data for regulatory review and action while continuing the trial to address a primary hypothesis. PMID- 29793354 TI - A potential biotechnological process for the sustainable production of vitamin K1. AB - The primary objective of this review is to propose an approach for the biosynthesis of phylloquinone (vitamin K1) based upon its known sources, its role in photosynthesis and its biosynthetic pathway. The chemistry, health benefits, market, and industrial production of vitamin K are also summarized. Vitamin K compounds (K vitamers) are required for the normal function of at least 15 proteins involved in diverse physiological processes such as coagulation, tissue mineralization, inflammation, and neuroprotection. Vitamin K is essential for the prevention of Vitamin K Deficiency Bleeding (VKDB), especially in neonates. Increased vitamin K intake may also reduce the severity and/or risk of bone fracture, arterial calcification, inflammatory diseases, and cognitive decline. Consumers are increasingly favoring natural food and therapeutic products. However, the bulk of vitamin K products employed for both human and animal use are chemically synthesized. Biosynthesis of the menaquinones (vitamin K2) has been extensively researched. However, published research on the biotechnological production of phylloquinone is restricted to a handful of available articles and patents. We have found that microalgae are more suitable than plant cell cultures for the biosynthesis of phylloquinone. Many algae are richer in vitamin K1 than terrestrial plants, and algal cells are easier to manipulate. Vitamin K1 can be efficiently recovered from the biomass using supercritical carbon dioxide extraction. PMID- 29793355 TI - Causalities. PMID- 29793356 TI - Ongoing pregnancies in patients with unexplained recurrent pregnancy loss: adverse obstetric outcomes. AB - To investigate the incidence of adverse pregnancy outcomes in couples with an unexplained Recurrent Pregnancy Loss (RPL) history, a retrospective cohort study was conducted between 2014 and 2015. The study group (A) included couples with an unexplained RPL, and the control group (B) was composed of couples who attended the Low-Risk Antenatal Unit during the same period. On the other hand, 53 couples were included in the study group (A) and on the other hand, 65 in the control group (B). Women with previous unexplained recurrent pregnancies loss had a significantly increased risk of gestational diabetes with 12 cases (22.6%) in the study group and 3 cases (4.6%) in the control (OR: 6.048; 95% CI: 1.607-22.762; p = 0.007). A slight increase in the risk of preterm delivery and hepatic cholestasis was observed in the study group (6 cases, 11.3%, in study group and 1 case, 1.5% in the controls (OR: 8.170; 95% CI: 0.951-70.158; p = 0.0555). Women with a history of RPL delivered more frequently by caesarean section (OR: 3.252; 95% CI: 1.460-7.241; p = 0.0039). Women with a history of RPL were at an increased risk for adverse pregnancy outcomes, mainly gestational diabetes. Therefore, a closer surveillance during the antenatal period is recommended in this group of patients. PMID- 29793357 TI - Large-Scale Food Fortification and Biofortification in Low- and Middle-Income Countries: A Review of Programs, Trends, Challenges, and Evidence Gaps. AB - BACKGROUND: Food fortification and biofortification are well-established strategies to address micronutrient deficiencies in vulnerable populations. However, the effectiveness of fortification programs is not only determined by the biological efficacy of the fortified foods but also by effective and sustainable implementation, which requires continual monitoring, quality assurance and control, and corrective measures to ensure high compliance. OBJECTIVE: To provide an overview of efficacy, effectiveness, economics of food fortification and biofortification, and status of and challenges faced by large scale food fortification programs in low- and middle-income countries (LMIC). METHODS: A literature review of PubMed publications in English from 2000 to 2017, as well as gray literature, targeting nongovernmental organizations whose work focuses on this topic, complemented by national reports and a "snowball" process of citation searching. The article describes remaining technical challenges, barriers, and evidence gap and prioritizes recommendations and next steps to further accelerate progress and potential of impact. RESULTS: The review identifies and highlights essential components of successful programs. It also points out issues that determine poor program performance, including lack of adequate monitoring and enforcement and poor compliance with standards by industry. CONCLUSIONS: In the last 17 years, large-scale food fortification initiatives have been reaching increasingly larger segments of populations in LMIC. Large-scale food fortification and biofortification should be part of other nutrition-specific and nutrition-sensitive efforts to prevent and control micronutrient deficiencies. There are remaining technical and food system challenges, especially in relation to improving coverage and quality of delivery and measuring progress of national programs. PMID- 29793359 TI - Molecular cell biology and advanced microscopy: an interview with Joshua Z. Rappoport. AB - Dr Joshua Z Rappoport, PhD, speaks to Nawsheen Boodhun, Managing Editor. Rappoport completed his bachelor's degree in Biology at Brown University (RI, USA). He then went on to earn a PhD from the Program in Mechanisms of Disease and Therapeutics at the Mount Sinai School of Medicine Graduate School of Biological Sciences of New York University (USA). Rappoport spent the early parts of his career working as a postdoctoral researcher at the Laboratory of Cellular Biophysics based in The Rockefeller University (NY, USA). He was subsequently recruited as a tenured faculty member to work as part of the School of Biosciences at the University of Birmingham (UK). 2014 marked the return of Rappoport to the USA, where he is currently a Research Professor in Molecular Cell Biology at the Northwestern University Feinberg School of Medicine (IL, USA). He is also the Director of the Center for Advanced Microscopy (CAM) and Nikon Imaging Center (NIC), a large core facility consisting of eight members of staff that support around 200 different laboratories. PMID- 29793358 TI - The Association Between beta-Blocker Use and Cardiorespiratory Fitness: The Maastricht Study. AB - PURPOSE: beta-Blockers (BBs) have been associated with a reduced cardiorespiratory fitness (CRF). This is possibly caused by inhibition of beta2 receptors in the airways. However, there are limited data available on beta receptor selectivity and CRF. We therefore aimed to assess the association between BB use and CRF and to assess the association between beta-receptor selectivity and CRF. METHODS: Participants in the Maastricht Study were aged between 40 and 75 years. Exposure to BB use was determined by use of pharmacy records. General linear models were used to obtain adjusted means of 2 proxies for CRF: covered distance during the 6-minute walk test (6MWT) and estimated maximum power output adjusted for body mass ( Wmax kg-1) during the submaximal cycle ergometer test. Adjusted means were compared between current, past, and never BB users. Current users were subsequently stratified by beta-receptor selectivity and dose. RESULTS: Compared to never use, current use was associated with a lower CRF, based on the 6MWT (current use: 569.7 m; never use: 580.4 m [ P = .010]), but not based on the cycling test (current use: 2.14 W kg-1; never use: 2.13 W kg-1 [ P = .690]). There was no difference between current selective and current nonselective BB use. CONCLUSION: beta-Blockers use was associated with CRF based on the 6MWT but not the cycling test. There was no difference between current selective and nonselective BB users, possibly due to the small number of nonselective BB users, differential underlying diseases, other pharmacological properties, and limitations related to the proxies of the outcome. PMID- 29793360 TI - Protein analysis: key to the future. AB - Protein analysis is crucial to elucidating the function of proteins and understanding the impact of their presence, absence and alteration. This is key to advancing knowledge about diseases, providing the opportunity for biomarker discovery and development of therapeutics. In this issue of Tech News, Nawsheen Boodhun explores the various means of protein analysis. PMID- 29793361 TI - A probe directed recombinase amplification assay for detection of MTHFR A1298C polymorphism associated with congenital heart disease. AB - Single nucleotide polymorphisms (SNPs) play an important role in susceptibility to complex diseases, treatment efficacy and adverse drug responses. Conventional methods to detect SNPs are usually based on PCR or DNA sequencing, which are typically time-consuming and require sophisticated equipment. In this proof-of concept study, a probe-directed recombinase amplification (PDRA) assay was developed to detect the A1298C polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR). The PDRA assay included two real-time reactions to detect the A and C nucleotides of A1298C polymorphism. Each reaction contained only one primer and one probe and was finished at 39 degrees C within 35 min. The results of genotyping of 150 clinical samples using PDRA were completely consistent with those by direct sequencing. Additionally, when the 1000 Genomes Project HCB frequencies were used as the control group, MTHFR A1298C was found to be associated with congenital heart disease. In conclusion, the proposed novel PDRA assay is a valuable tool for the detection of SNPs and demonstrates significant potential to be widely applicable in both research and clinical settings. PMID- 29793362 TI - Quantifying cell free DNA in urine: comparison between commercial kits, impact of gender and inter-individual variation. AB - DNA can enter the blood circulation from living cells by extracellular vesicles or at cell death, and pass into urine through the kidney barrier. Urine can be collected non-invasively, making it an interesting source of cell-free DNA (cfDNA) for research studies and ultimately for clinical diagnostics. However, there is currently a lack of data on the quantity and variability of cfDNA in urine. Here, we benchmark two commercial urine cfDNA isolation kits with respect to the quantity of DNA, the labor time, and cost. The results show distinctive differences between each kit. Furthermore, the cfDNA amount from the same probands varied strongly from day to day and may be higher in female samples than in male samples (p = 0.003). PMID- 29793363 TI - Detection of proteolytic activity by covalent tethering of fluorogenic substrates in zymogram gels. AB - Current zymographic techniques detect only a subset of known proteases due to the limited number of native proteins that have been optimized for incorporation into polyacrylamide gels. To address this limitation, we have developed a technique to covalently incorporate fluorescently labeled, protease-sensitive peptides using an azido-PEG3-maleimide crosslinker. Peptides incorporated into gels enabled measurement of MMP-2, -9, -14, and bacterial collagenase. Sensitivity analysis demonstrated that use of peptide functionalized gels could surpass detection limits of current techniques. Finally, electrophoresis of conditioned media from cultured cells resulted in the appearance of several proteolytic bands, some of which were undetectable by gelatin zymography. Taken together, these results demonstrate that covalent incorporation of fluorescent substrates can greatly expand the library of detectable proteases using zymographic techniques. PMID- 29793364 TI - You asked, we listened - get ready for more tips, tricks & discussion from BioTechniques. PMID- 29793365 TI - The association between neonatal head circumference and second stage duration. AB - PURPOSE: To determine if head circumference (HC) is an independent factor influencing second stage duration stratified by parity and epidural use. MATERIALS AND METHODS: A retrospective cohort analysis of all live, singleton, term (37-42 weeks) vaginal deliveries in one university affiliated medical center (2012-2014). Exclusion criteria included operative deliveries due to fetal distress, major fetal anomalies/chromosomal abnormalities or cases with missing anthropometric data. Maternal demographics, labor characteristics and neonatal anthropometrics including birth weight and HC were retrieved. Multivariate linear regression was utilized to evaluate the association between HC and second stage duration. Analysis was stratified into four groups by parity and epidural use. RESULTS: Of the 16 240 singleton vaginal deliveries during study period, 12 428 deliveries met inclusion criteria. Stratification by parity and epidural analgesia yielded four groups: 3337 (26.9%), 735 (5.9%), 5099 (41.0%) and 3257 (26.2%) deliveries - nullipara with/without epidural and multipara with/without epidural, respectively. In all groups, a large neonatal HC was significantly and independently associated with longer second stage duration: nullipara with epidural (beta 10.06, 95% CI 7.75-12.37), nullipara without epidural (beta 7.58, 95% CI 4.73-10.43), multipara with epidural (beta 4.64, 95%CI 3.47-5.8) and multipara without epidural (beta 1.35, 95% CI 0.76-1.94), p < .001 for all. Birth weight was not associated with second stage duration in any of the groups (p > .05). CONCLUSION: Large neonatal HC is significantly associated with longer second stage duration. PMID- 29793366 TI - Noninvasive prenatal testing (NIPT) detects variant of Turner syndrome not detectable by fluorescent in situ hybridization. AB - INTRODUCTION: Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain microdeletions which include cri-du-chat, DiGeorge, 1p36, Angelman, and Prader-Willi syndromes in comparison to the available screening methods. Prenatal screening of Turners syndrome is possible by ultrasound in certain conditions only. Recently benefits of early detection and treatment of Turners syndrome has been emphasized, enforcing on accurate and early screening prenatally. CASE DETAILS: The current case emphasizes on the reliability of NIPT testing which comes with an advantage of early screening. A 24-year-old primi gravida was referred for NIPT as she tested for high risk on biochemical screening. The PanoramaTM NIPT results showed low risk for trisomies, 21, 18, and 13 but high risk of monosomy X and was advised confirmatory amniocentesis. The fluorescence in situ hybridization (FISH) report revealed no numerical abnormality detected for any of the five chromosomes tested. On receiving this discordant report, the sample was rerun for NIPT, to rule out any laboratory related issues. The result obtained on a rerun was consistent with the first report and showed monosomy X again. The karyotype report was available three weeks later and a rare variant of Turners syndrome was identified. DISCUSSION: PanoramaTM NIPT considers single nucleotide polymorphisms spread across the chromosomes for analysis, different variants of aneuploidy can be picked up in comparison to FISH, similar to the current case wherein it could not as it was a centromeric probe. Reported first case of X chromosome variant detected by NIPT confirmed by karyotyping, missed by FISH. PMID- 29793368 TI - Maxillo-occipital line: a sonographic marker for screening of open spina bifida in the first trimester of pregnancy. AB - OBJECTIVE: To describe a new first-trimester sonographic landmark the maxillo occipital line which may be useful for early screening of open spina bifida. METHODS: Maxillo-occipital line was prospectively evaluated in 100 low-risk pregnancies at the time of first-trimester sonographic screening examination between 11 and 13 + 6 weeks' gestation. All the pregnant women subsequently had a normal second-trimester scan and normal outcomes. Midsagittal brain images of 14 fetuses with known diagnosis of open spina bifida were evaluated retrospectively to review the maxillo-occipital line. RESULTS: None of the 100 fetuses evaluated prospectively with the maxillo-occipital line below the junction of the midbrain and brain stem were affected by open spina bifida. The aqueduct of Silvius to occiput distance measurement was not obtained in five cases. In all, 14 cases with a diagnosis of open spina bifida, the junction between the midbrain and brain stem, were below the maxilla-occipital line. CONCLUSION: Maxillo-occipital line is an easy addition to the evaluation of first-trimester screening of open spina bifida. Further studies are needed to determine the false-positive and false-negative rates of this technique. PMID- 29793367 TI - Dimethylarginine dimethylaminohydrolase (DDAH) overexpression enhances wound repair in airway epithelial cells exposed to agricultural organic dust. AB - OBJECTIVE: Workers exposed to dusts from concentrated animal feeding operations have a high prevalence of pulmonary diseases. These exposures lead to chronic inflammation and aberrant airway remodeling. Previous work shows that activating cAMP-dependent protein kinase (PKA) enhances airway epithelial wound repair while activating protein kinase C (PKC) inhibits wound repair. Hog barn dust extracts slow cell migration and wound repair via a PKC-dependent mechanism. Further, blocking nitric oxide (NO) production in bronchial epithelial cells prevents PKA activation. We hypothesized that blocking an endogenous NO inhibitor, asymmetric dimethylarginine, by overexpressing dimethylarginine dimethylaminohydrolase mitigates the effects of hog dust extract on airway epithelial would repair. MATERIALS/METHODS: We cultured primary tracheal epithelial cells in monolayers from both wild-type (WT) and dimethylarginine dimethylaminohydrolase overexpressing C57Bl/6 (DDAH1 transgenic) mice and measured wound repair using the electric cell impedance sensing system. RESULTS: Wound closure in epithelial cells from WT mice occurred within 24 h in vitro. In contrast, treatment of the WT cell monolayers with 5% hog dust extract prevented significant NO-stimulated wound closure. In cells from DDAH1 transgenic mice, control wounds were repaired up to 8 h earlier than seen in WT mice. A significant enhancement of wound repair was observed in DDAH cells compared to WT cells treated with hog dust extract for 24 h. Likewise, cells from DDAH1 transgenic mice demonstrated increased NO and PKA activity and decreased hog dust extract-stimulated PKC. DISCUSSION/CONCLUSION: Preserving the NO signal through endogenous inhibition of asymmetric dimethylarginine enhances wound repair even in the presence of dust exposure. PMID- 29793369 TI - Gaussian Discriminant Analysis for Optimal Delineation of Mild Cognitive Impairment in Alzheimer's Disease. AB - Over the past few years, several approaches have been proposed to assist in the early diagnosis of Alzheimer's disease (AD) and its prodromal stage of mild cognitive impairment (MCI). Using multimodal biomarkers for this high-dimensional classification problem, the widely used algorithms include Support Vector Machines (SVM), Sparse Representation-based classification (SRC), Deep Belief Networks (DBN) and Random Forest (RF). These widely used algorithms continue to yield unsatisfactory performance for delineating the MCI participants from the cognitively normal control (CN) group. A novel Gaussian discriminant analysis based algorithm is thus introduced to achieve a more effective and accurate classification performance than the aforementioned state-of-the-art algorithms. This study makes use of magnetic resonance imaging (MRI) data uniquely as input to two separate high-dimensional decision spaces that reflect the structural measures of the two brain hemispheres. The data used include 190 CN, 305 MCI and 133 AD subjects as part of the AD Big Data DREAM Challenge #1. Using 80% data for a 10-fold cross-validation, the proposed algorithm achieved an average F1 score of 95.89% and an accuracy of 96.54% for discriminating AD from CN; and more importantly, an average F1 score of 92.08% and an accuracy of 90.26% for discriminating MCI from CN. Then, a true test was implemented on the remaining 20% held-out test data. For discriminating MCI from CN, an accuracy of 80.61%, a sensitivity of 81.97% and a specificity of 78.38% were obtained. These results show significant improvement over existing algorithms for discriminating the subtle differences between MCI participants and the CN group. PMID- 29793370 TI - Evaluating Screening Tests for Depression in Post-Stroke Older Adults. AB - BACKGROUND: Uncertainty surrounds which screening test to use in older patients with poststroke depression, in whom symptoms of depression are more complex and often occur in conjunction with other comorbidities. We evaluated screening tests for depression among a cohort of older ambulatory individuals with comorbid ischemic heart disease and prior stroke. METHODS: We administered 4 depression screening instruments to 148 participants with ischemic heart disease and self reported stroke from The Heart and Soul Study. Instruments included the 10-item Center for Epidemiologic Studies Depression Scale (CES-D), 9-item and 2-item versions of the Patient Health Questionnaire (PHQ-9 and PHQ-2), and the Whooley questions, a 2-item yes/no questionnaire. We administered the computerized version of the National Institute of Mental Health Diagnostic Interview Schedule as a gold standard. RESULTS: Of the 148 participants, 35 (24%) had major depression. The Whooley questions demonstrated the highest sensitivity for detection (89%), followed by the CES-D (80%), PHQ-2 with cut point >=2 (79%), PHQ 9 (51%), and PHQ-2 with cut point >=3 (32%). The Whooley questions had a specificity of 0.66, a positive likelihood ratio of 2.61, and a negative likelihood ratio of 0.82. We observed no significant difference in the area under the receiver operating characteristic curve across the 4 instruments. CONCLUSION: In a cohort of ambulatory older adults with coronary heart disease and prior stroke, depression occurred in a fourth of the participants. The simple Whooley questions screening instrument can efficiently detect depression with a high sensitivity in this population, one representative of older patients commonly encountered within a primary care setting. PMID- 29793371 TI - Response to: Is there a superior simulator for human anatomy education? How virtual dissection can overcome the anatomic and pedagogic limitations of cadaveric dissection. PMID- 29793372 TI - The Dynamic Brain Networks of Motor Imagery: Time-Varying Causality Analysis of Scalp EEG. AB - Motor imagery (MI) requires subjects to visualize the requested motor behaviors, which involves a large-scale network that spans multiple brain areas. The corresponding cortical activity reflected on the scalp is characterized by event related desynchronization (ERD) and then by event-related synchronization (ERS). However, the network mechanisms that account for the dynamic information processing of MI during the ERD and ERS periods remain unknown. Here, we combined ERD/ERS analysis with the dynamic networks in different MI stages (i.e. motor preparation, ERD and ERS) to probe the dynamic processing of MI information. Our results show that specific dynamic network structures correspond to the ERD/ERS evolution patterns. Specifically, ERD mainly shows the contralateral networks, while ERS has the symmetric networks. Moreover, different dynamic network patterns are also revealed between the two types of MIs, in which the left-hand MIs exhibit a relatively less sustained contralateral network, which may be the network mechanism that accounts for the bilateral ERD/ERS observed for the left hand MIs. Similar to the network topologies, the three MI stages also appear to be characterized by different network properties. The above findings all demonstrate that different MI stages that involve specific brain networks for dynamically processing the MI information. PMID- 29793374 TI - Comment on: Prevalence of depressive symptoms among medical students taught using problem-based learning versus traditional methods. PMID- 29793373 TI - Surgical treatment of cervical subaxial intraspinal extradural cysts using a full endoscopic uniportal posterior approach. AB - PURPOSE: Symptomatic intraspinal extradural cysts of the cervical subaxial spine are rare, but usually require surgery. Conventional posterior decompression is the gold standard. However, there is increasing experience with endoscopic surgical techniques. The purpose of the study is to evaluate the technical implementation and outcomes of a full-endoscopic uniportal technique via the posterior approach in patients with symptomatic intraspinal extradural cysts of the cervical subaxial spine. METHODS: Seven consecutive patients with a subaxial location of symptomatic intraspinal extradural cysts were decompressed in a full endoscopic uniportal technique via the posterior approach between 2009 and 2015. Imaging and clinical data were collected in follow-up examinations for 18 months. RESULTS: In all cases, the cyst was completely removed and adequate decompression was achieved using the full-endoscopic uniportal technique. One patient developed a dural leak that was sutured and covered intraoperatively. No other complications requiring treatment were observed. All patients had a good clinical outcome with stable regression of the radicular and central nerve pain or neurological deficits. The imaging follow-up showed sufficient decompression in all cases. No evidence was found of increasing instability during the follow-up period. CONCLUSION: The full-endoscopic uniportal operation with a posterior approach allows the resection of the cyst and can minimize trauma and destabilization and has technical benefits and a low complication rate. It is an alternative surgical method that can offer advantages and is considered by the authors to be the surgical technique of choice for cervical subaxial intraspinal extradural cysts. PMID- 29793375 TI - Infective Endocarditis Associated With Varicella Zoster Virus Following Aortic Valve Repair. AB - We describe the management and clinical course of two children with congenital bicuspid aortic valve. Neo-tricuspidization was performed in one case using CardioCel leaflets and two cusps were formed from CardioCel and grafted alongside one native leaflet in the other. Both patients developed bacterial endocarditis associated with varicella zoster virus infection and required a second surgical procedure. PMID- 29793376 TI - Longitudinal assessments in continuing specialty certification and lifelong learning. AB - Longitudinal assessment (LA) involves the regular, spaced delivery of a limited number of questions on practice relevant content on a computer or mobile internet platform. Depending on the platform, participants may indicate relevance of the content to their practice and confidence in their answer prior to receiving immediate feedback (including critiques) on each question. Individual dashboards may be included to assist participants in tracking progress and identifying areas of strength and weaknesss across a content blueprint. This paper provides an overview of the theoretical underpinnings underlying LA programs, briefly describes current uses of LA in medicine and suggests areas for evaluating the role of LA in continuing medical specialty certification and continuing professional development. PMID- 29793377 TI - Projected impact of a multigene pharmacogenetic test to optimize medication prescribing in cardiovascular patients. AB - AIM: To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing. MATERIALS & METHODS: A retrospective analysis was conducted with 122 cardiac catheterization laboratory patients undergoing angiography for eligibility of potential PGx-guided interventions that could have occurred if multigene PGx information was pre-emptively available at the time of the procedure. Medication data and presence of actionable at-risk genotypes were used to determine eligibility of a PGx intervention. RESULTS: 20% of the study population (n = 24) would have qualified for at least one PGx-based medication intervention per US FDA or Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines within 6 months of their cardiac catheterization procedure. Commonly encountered gene-drug pairs for these interventions included: CYP2C19 for clopidogrel and antidepressants, CYP2D6 for antidepressants and codeine, SLCO1B1 for simvastatin, and VKORC1/CYP2C9 for warfarin. CONCLUSION: Pre-emptive use of a multigene PGx test in the cardiac catheterization laboratory offers potential to reduce adverse medication outcomes. PMID- 29793378 TI - Injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release. AB - A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa.s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering. PMID- 29793379 TI - Kawasaki Disease in a Patient With Williams Syndrome. AB - Kawasaki disease can be difficult to diagnose in infants, putting them at higher risk for developing coronary artery dilatation. It can be even more difficult to diagnose in the setting of preexisting cardiac anomalies such as those found in Williams syndrome. We present a case of a three-month-old male with Williams syndrome with rapidly developing giant coronary aneurysms due to Kawasaki disease. This case demonstrates the importance of repeat echocardiography in diagnosing incomplete Kawasaki disease in infants. We speculate that elastin changes, as present in Williams syndrome, may put affected children at higher risk for development of giant coronary arteries should they acquire Kawasaki disease. PMID- 29793380 TI - Diffusion of innovation and longitudinal integrated clerkships: Results of the clerkship directors in internal medicine annual survey. AB - PURPOSE: Longitudinal integrated clerkships (LICs) are innovative educational models that emphasize medical student continuity with patients, preceptors, peers, and health systems. We characterize LIC growth in the US and interpret the growth using Rogers' Diffusion of Innovation Theory. METHODS: In 2015, we surveyed 123 US allopathic medical schools affiliated with Clerkship Directors in Internal Medicine (CDIM). The organization's annual survey was supplemented with questions aimed to quantify the number of current and planned LICs and to determine the intended purpose of starting LICs. RESULTS: Of the 94 (out of 123 possible) schools which were responding, 35 (37%) have at least one LIC of six months or greater; of these 20 are year-long. Nineteen schools are engaged in planning a new LIC or increasing the number of students in an LIC. At least 45 (48%) responding schools will have LICs in future years. Respondents report implementing LICs to foster continuity of care, support patient-centeredness, advance inter-professional education, and address workforce shortages. CONCLUSIONS: The number of LICs is increasing across the US. We considered the data through the lens of Diffusion of Innovation Theory, speculated that LIC growth has reached "critical mass," and considered why the LIC innovation may be self-sustaining. PMID- 29793381 TI - Feasibility of Patient-Reported Outcomes Measurement Information System (PROMIS(r)) computerized adaptive tests in systemic lupus erythematosus outpatients. AB - Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS(r)) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience. Differences in socio-demographic and clinical characteristics between participants and non-participants were evaluated. Results A total of 204 (86%) of 238 socioeconomically and racially diverse SLE patients completed PROMIS CATs. There were no significant differences between participants and non-participants. Time constraints were cited most frequently as reasons for non-participation. More than 75% of individuals submitted positive comments, including approval of the content and format of questions, and the survey's promotion of self-reflection. A minority of participants cited challenges, most often related to question phrasing (8%) and technical difficulties (6%). Conclusions The administration of PROMIS CATs was feasible and positively received in a diverse cohort of SLE outpatients. Neither socio-demographic nor disease characteristics were significant barriers to successful completion of PROMIS CATs. PROMIS CATs have great potential for efficiently measuring important patient-centered outcomes in routine clinical care of a wide range of SLE patients. PMID- 29793382 TI - Analysis of IL-6 and IL-1beta release in cryopreserved pooled human whole blood stimulated with endotoxin. AB - To overcome the lack of availability of fresh human whole blood for pyrogen detection, we explored the feasibility of utilizing cryopreserved pooled human blood to detect the responses of the pro-inflammatory cytokines IL-6 and IL-1beta to LPS. Whole blood was obtained from five donors and incubated with LPS. The quantities of pro-inflammatory cytokines were measured using ELISA, and the results were compared among the samples. After the blood was cryopreserved with Dimethyl sulfoxide (DMSO) (10% v/v) and stored for 4 mo at -196C, the detection limits of the IL-6/IL-1beta responses to LPS were 0.2/0.4 endotoxin units (EU)/ml, respectively, and IL-6/IL-1beta release increased in response to LPS in a dose-dependent manner. When these experiments were performed in three separate laboratories, the within-laboratory reproducibility of the IL-6/IL-1beta responses was 100%/86.7%, 93.3%/100%, and 86.7%/80%, and the inter-laboratory reproducibility was 92.9%/85.7%, 64.3%/63.6%, and 57.1%/66.7%, respectively. The sensitivity (the probability of correctly classifying positive samples) and specificity (the probability of correctly classifying negative samples) of the IL 6/IL-1beta tests were 81.7%/82.5% and 100%/100%, respectively. The results of this study suggest that cryopreserved pooled blood is a convenient and viable alternative for evaluating in vitro pyrogenicity. Additionally, maintaining cryopreserved pooled blood promotes safety for the user because it is released only after pretesting for infection parameters and has lower variation than fresh donations from a variety of donors. PMID- 29793383 TI - Repair of Sinus Venosus Defect and Anomalous Pulmonary Veins Associated With Vein of Galen Malformation. AB - Sinus venosus defect (SVD) is a deficiency in the sinus venosus portion of the atrium, often associated with partial anomalous pulmonary venous connections. In patients with vein of Galen malformation (VGAM), SVD provides a unique challenge with respect to embolization treatment. In our case, the child had percutaneous device closure of the SVD prior to VGAM embolization. Nine years later, he required surgical removal of the SVD device and Warden procedure due to progressive right-sided cardiac enlargement. PMID- 29793384 TI - Long-term experiences of being a simulation-educator: A multinational interview study. AB - The long-term reactions, experiences and reflections of simulation educators have not been explored. In a semistructured, exploratory interview study, the experiences of simulation educators in either Advanced Life Support (ALS) or Crisis Resource Management (CRM) courses in Denmark, Norway and the USA were analyzed. Three overarching themes were identified: (1) general reflections on simulation-based teaching, (2) transfer of knowledge and skills from the simulation setting to clinical settings and (3) more overarching transformations in simulation educators, simulation participants, and the healthcare system. Where ALS was deemed as high on the efficiency dimension of learning, CRM courses were described as high on the innovation dimension. General reflections, transfer and transformations described were related to differences in course principles. The results are relevant for career planning, faculty development and understanding simulation as social practice. PMID- 29793385 TI - Box-ticking and Olympic high jumping - Physicians' perceptions and acceptance of national physician validation systems. AB - PURPOSE: National physician validation systems aim to ensure lifelong learning through periodic appraisals of physicians' competence. Their effectiveness is determined by physicians' acceptance of and commitment to the system. This study, therefore, sought to explore physicians' perceptions and self-reported acceptance of validation across three different physician validation systems in Europe. MATERIALS AND METHODS: Using a constructivist grounded-theory approach, we conducted semi-structured interviews with 32 respiratory specialists from three countries with markedly different validation systems: Germany, which has a mandatory, credit-based system oriented to continuing professional development; Denmark, with mandatory annual dialogs and ensuing, non-compulsory activities; and the UK, with a mandatory, portfolio-based revalidation system. We analyzed interview data with a view to identifying factors influencing physicians' perceptions and acceptance. RESULTS: Factors that influenced acceptance were the assessment's authenticity and alignment of its requirements with clinical practice, physicians' beliefs about learning, perceived autonomy, and organizational support. CONCLUSIONS: Users' acceptance levels determine any system's effectiveness. To support lifelong learning effectively, national physician validation systems must be carefully designed and integrated into daily practice. Involving physicians in their design may render systems more authentic and improve alignment between individual ambitions and the systems' goals, thereby promoting acceptance. PMID- 29793386 TI - CPD? What happened to CME? CME and beyond. AB - Continuing medical education (CME) has been evolving into continuing professional development (CPD) and more recently into competency-based continuing professional development (CBCPD). We will describe this progression and the consequent changes in CPD programs developed by educators, appraise emerging challenges in CPD, propose strategies to overcome them and conclude by recommending research in CPD as the best way to consistently guide effective CPD programs and systems aligned with the public healthcare needs and expectations. PMID- 29793387 TI - Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial. AB - Introduction The aim of this study was to assess the impact of home-based telehealth monitoring on health outcomes, quality of life and costs over 12 months for patients with diabetes and/or chronic obstructive pulmonary disease (COPD) who were identified as being at high risk of readmission to hospital. Methods This pilot study was a randomised controlled trial combined with an economic analysis to examine the outcomes of standard care versus home-based telehealth for people with diabetes and/or COPD who were at risk of hospital readmission within one year. The primary outcomes were (i) hospital admission and length of stay (LOS); and (ii) health-related quality of life (HRQOL); and the secondary outcomes were (i) health-related clinical outcomes; (ii) anxiety and depression scores; and (iii) health literacy. The costs of the intervention and hospitalisations were included. Results A total of 86 and 85 participants were randomised to the intervention and control groups respectively. The difference between groups in hospital LOS was -3.89 (95% confidence interval (CI): -9.40, 1.62) days, and for HRQOL, 0.09 (95% CI: 0.05, 0.14) in favour of the telehealth monitoring group. There was a saving of AUD$6553 (95% CI: -12145, -961) in the cost of hospitalisation over 12 months, which offset the increased cost of tele monitoring. The intervention group showed an improvement in anxiety, depression and health literacy at 12 months, and in the diabetes group, a reduction in microalbuminuria. Discussion The telehealth monitoring intervention improved patient's health outcomes and quality of life at no additional cost. PMID- 29793389 TI - Restraint of adults with intellectual disabilities: A critical review of the prevalence and characteristics associated with its use. AB - BACKGROUND: As part of their care, adults with intellectual disabilities are often subject to restrictive interventions including restraint. METHOD: A review examining the prevalence of restraint use with people with intellectual disabilities and the characteristics associated with its use. RESULTS: The seven papers identified used quantitative methodologies and had cross-sectional designs. Prevalence rates of restraint ranged from 11% to 78%, multiple forms of restraint were common. Most studies focused on characteristics within the person with an intellectual disability, three considered external factors. Challenging behaviour was the most consistent characteristic associated with the use of restraint, but how this was defined varied. CONCLUSIONS: The review highlights a need for more consistent means of defining and measuring restraint and its associated characteristics. Future research into this area may also want to focus on the context of restraint such as whether it is the least restrictive option used. PMID- 29793388 TI - Impact of patient-centred home telehealth programme on outcomes in heart failure. AB - Background Telehealth is a promising intervention to reduce readmissions and healthcare-associated costs in patients with heart failure. Methods We performed a retrospective analysis of the impact of telehealth on 197 heart failure patients who had successfully completed one year of home telehealth monitoring following a heart failure admission as part of a clinically mandated programme at a Veterans Affairs Medical Center. Outcomes were compared both within the group (one year before and one year after home telehealth monitoring), and to a contemporary control cohort of 870 heart failure patients who were admitted but not enrolled in home telehealth. The following outcomes were analysed: admissions for any cause, heart failure admissions, total hospital days per patient, average length of stay per admission, urgent care and emergency room visits, and primary care visits. Results Both the home telehealth and control cohorts consisted of older male patients. Total hospital days per patient was significantly reduced by home telehealth monitoring in the home telehealth group (2.4 +/- 3.5) in comparison to the previous year without monitoring (4.1 +/- 4.6, p < 0.0001) and to the control group (3.8 +/- 5.3, p < 0.001). A significantly lower admission rate (1.1 +/- 1.6) and length of stay (5.7 +/- 11.3 days) were observed during home telehealth monitoring within the home telehealth group compared to the prior year (1.6 +/- 1.7, p < 0.05 and 9.5 +/- 14 days, p < 0.01 respectively) but not in comparison with the control group (1.4 +/- 2.0, p < 0.07). The home telehealth group also had a significantly lower length of stay when compared to the control group (5.7 +/- 11.3 vs 9.0 +/- 14.9, p < 0.01). The number of urgent care and emergency room visits, or primary care visits, was not significantly different during home telehealth monitoring as compared to the prior year. Conclusions Personalised and patient-centred home telehealth monitoring in heart failure patients was successful in reducing outcomes without an increase in outpatient and urgent care visits. PMID- 29793390 TI - Effectiveness of oral appliances versus continuous positive airway pressure in treatment of OSA patients: An updated meta-analysis. AB - Objective To update the meta-analysis comparing the effectiveness of oral appliance (OA) with continuous positive airway pressure (CPAP) in treating patients with obstructive sleep apnea (OSA). Methods PubMed, ISI Web of Knowledge, Ovid, EBSCO Dentistry & Oral Science Source, The Cochrane Library, and Embase database were searched for RCTs until 23 May 2017. Meta-analyses were performed using RevMan 5.3. Results Sixteen RCTs were included. Compared with OA, CPAP significantly decreased AHI, min SaO2, ARI, ESS (p < 0.05), with no significant difference in REM%, FOSQ, BP (p >= 0.05). OA significantly improved REM% in the severe groups and ESS in the adjustable OA group (p < 0.05). OA shared greater preference. Conclusion Even though CPAP can better decrease the severity of OSA, more patients opted for OA, which showed better results in severe patients, especially adjustable OA. PMID- 29793391 TI - Medication management for community palliative care patients and the role of a specialist palliative care pharmacist: A qualitative exploration of consumer and health care professional perspectives. AB - BACKGROUND: Pharmacists have a key role to play in optimisation of medication regimens and promotion of medication safety. The role of specialist pharmacists as part of the multidisciplinary palliative care team, especially in the primary care setting, is not widely recognised. AIM: To explore the perspectives of stakeholders about the gaps in the current model of community palliative care services in relation to medication management and to assess their opinions pertaining to the role of a specialist palliative care pharmacist in addressing some of those gaps. DESIGN: Qualitative study utilising three focus groups involving 20 stakeholders. Thematic analysis was carried out using a framework approach and interpreted in the context of the Chronic Care Model for improving primary care for patients with chronic illness. SETTING/PARTICIPANTS: Setting was a large regional Australian palliative care service. Participants included palliative care consumers and clinicians specifically patients, caregivers, physicians, nurses and pharmacists. RESULTS: Five major themes emerged from the focus groups: access to resources, medicines and information; shared care; challenges of polypharmacy; informal caregiver needs and potential roles of a palliative care pharmacist. Gaps in access to medicines/resources, training for generalist practitioners, communication between treating teams and lack of support for patients and carers were cited as factors adversely impacting medication management in community-based palliative care. CONCLUSION: While community-based palliative care is an essential aspect of meeting the health care demands of an ageing society, the current model has several gaps and limitations. An appropriately qualified and skilled pharmacist within the palliative care team may help to address some of the gaps in relation to medication access and appropriateness. PMID- 29793392 TI - Cohort trends in duration of obesity in the United States, 1925-89: Estimates from cross-sectional data. AB - This paper introduces the metric 'mean duration of obesity' to measure the average number of years lived with obesity in a population. A procedure was developed to estimate duration from periodic cross-sectional surveys. For annual cohorts born in the United States between 1925 and 1989, I estimated a logit model to derive age-cohort-specific probabilities of overweight and obesity (body mass index 25 to <30 and [Formula: see text]30, respectively), and applied life table techniques to convert these into person-years. Duration of obesity by age 50 increased fourfold from 3.58 to 14.35 years. The rate of increase was stronger across the 1945-79 and 1980-89 cohorts than the 1925-44 cohorts. The trend was driven by increased risks of obesity among children: age groups under 20 were responsible for 31 per cent of the duration increase between the 1930 and 1960 cohorts, but 72 per cent between the 1960 and 1985 cohorts. PMID- 29793393 TI - Reducing costs at the end of life through provider incentives for hospice care: A retrospective cohort study. AB - BACKGROUND: Costs of medical care have been found to be highest at the end of life. AIM: To evaluate the effect of provider reimbursement for hospice care on end-of-life costs. DESIGN: The policy expanded access to hospice care for end stage renal disease patients, a policy previously limited to cancer patients only. This study employed a difference-in-differences analysis using a generalized linear model. The main outcome is inpatient expenditures in the last 30 days of life. SETTING/PARTICIPANTS: A cohort of 151,509 patients with chronic kidney disease or cancer, aged 65 years or older, who died between 2005 and 2012 in the National Health Insurance Research Database, which contains all enrollment and inpatient claims data for Taiwan. RESULTS: Even as end-of-life costs for cancer are declining over time, expanding hospice care benefits to end-stage renal disease patients is associated with an additional reduction of 7.3% in end of-life costs per decedent, holding constant patient and provider characteristics. On average, end-of-life costs are also high for end-stage renal disease (1.88 times higher than those for cancer). The cost savings were larger among older patients-among those who died at 80 years of age or higher, the cost reduction was 9.8%. CONCLUSION: By expanding hospice care benefits through a provider reimbursement policy, significant costs at the end of life were saved. PMID- 29793395 TI - Enhancing Treatment Reengagement for Veterans With Serious Mental Illness: Evaluating the Effectiveness of SMI Re-Engage. AB - OBJECTIVE: This evaluation assessed the effectiveness of the Veterans Health Administration (VHA) program Reengaging Veterans With Serious Mental Illness in Treatment (SMI Re-Engage). The program serves veterans with serious mental illness who experience extended gaps in use of VHA care. METHODS: Propensity score-weighted survival analysis that adjusted for demographic, clinical, and utilization factors assessed whether being contacted via SMI Re-Engage predicted return to VHA care within 18 months of when clinicians received patient contact information and, among veterans contacted, whether return to VHA care was associated with mortality risk within the 18-month follow-up period. Among all veterans who returned to care, a post hoc propensity score-weighted logistic regression that adjusted for demographic, clinical, and utilization factors assessed whether being contacted via SMI Re-Engage was associated with returning to outpatient care versus inpatient or emergency care. RESULTS: Of veterans contacted (N=886), 42% returned to care, compared with 27% of veterans whom providers attempted to contact but could not reach (N=2,059). When analyses adjusted for covariates, veterans who were contacted had a higher risk of returning to care (hazard ratio (HR)=3.40, 95% confidence interval [CI]=2.70 4.28). Among veterans contacted, the association between return to VHA care and mortality risk was not significant. Post hoc analyses for veterans who returned to care (N=941) indicated that being contacted (versus not being contacted) was associated with higher odds of returning to outpatient care (versus inpatient or emergency care) (odds ratio=2.42, CI=1.68-3.47). CONCLUSIONS: SMI Re-Engage contact facilitated return to VHA care. SMI Re-Engage exemplifies how population health strategies can address health care discontinuities among people with serious mental illness. PMID- 29793396 TI - Taking Legal Histories in Psychiatric Assessments. AB - People with mental illness are often disproportionately affected by the U.S. justice system, yet psychiatrists and other mental health professionals may avoid or feel uncomfortable talking with patients about legal history. This column examines why legal history is relevant to psychiatric assessments and provides guidance for talking with patients about these issues. Key aspects of taking a legal history are reviewed, including suggested questions, the role of collateral information, and considerations for medicolegal documentation. Developing skills in taking patients' legal histories may equip clinicians to better understand their patients' stories and to provide more effective psychiatric care. PMID- 29793397 TI - Mobile Health (mHealth) Versus Clinic-Based Group Intervention for People With Serious Mental Illness: A Randomized Controlled Trial. AB - OBJECTIVE: mHealth approaches that use mobile phones to deliver interventions can help improve access to care for people with serious mental illness. The goal was to evaluate how mHealth performs against more traditional treatment. METHODS: A three-month randomized controlled trial was conducted of a smartphone-delivered intervention (FOCUS) versus a clinic-based group intervention (Wellness Recovery Action Plan [WRAP]). Participants were 163 clients, mostly from racial minority groups and with long-term, serious mental illness (schizophrenia or schizoaffective disorder, 49%; bipolar disorder, 28%; and major depressive disorder, 23%). Outcomes were engagement throughout the intervention; satisfaction posttreatment (three months); and improvement in clinical symptoms, recovery, and quality of life (assessed at baseline, posttreatment, and six months). RESULTS: Participants assigned to FOCUS were more likely than those assigned to WRAP to commence treatment (90% versus 58%) and remain fully engaged in eight weeks of care (56% versus 40%). Satisfaction ratings were comparably high for both interventions. Participants in both groups improved significantly and did not differ in clinical outcomes, including general psychopathology and depression. Significant improvements in recovery were seen for the WRAP group posttreatment, and significant improvements in recovery and quality of life were seen for the FOCUS group at six months. CONCLUSIONS: Both interventions produced significant gains among clients with serious and persistent mental illnesses who were mostly from racial minority groups. The mHealth intervention showed superior patient engagement and produced patient satisfaction and clinical and recovery outcomes that were comparable to those from a widely used clinic-based group intervention for illness management. PMID- 29793399 TI - New research makes up for lost time on feline tick paralysis. PMID- 29793398 TI - The Influence of Team Functioning and Workload on Sustainability of Trauma Focused Evidence-Based Psychotherapies. AB - OBJECTIVE: It has been over a decade since the U.S. Department of Veterans Affairs (VA) began formal dissemination and implementation of two trauma-focused evidence-based psychotherapies (TF-EBPs). The objective of this study was to examine the sustainability of the TF-EBPs and determine whether team functioning and workload were associated with TF-EBP sustainability. METHODS: This observational study used VA administrative data for 6,251 patients with posttraumatic stress disorder (PTSD) and surveys from 78 providers from 10 purposefully selected PTSD clinical teams located in nine VA medical centers. The outcome was sustainability of TF-EBPs, which was based on British National Health System Sustainability Index scores (possible scores range from 0 to 100.90). Primary predictors included team functioning, workload, and TB-EBP reach to patients with PTSD. Multiple linear regression models were used to examine the influence of team functioning and workload on TF-EBP sustainability after adjustment for covariates that were significantly associated with sustainability. RESULTS: Sustainability Index scores ranged from 53.15 to 100.90 across the 10 teams. Regression models showed that after adjustment for patient and facility characteristics, team functioning was positively associated (B=9.16, p<.001) and workload was negatively associated (B=-.28, p<.05) with TF-EBP sustainability. CONCLUSIONS: There was considerable variation across teams in TF-EBP sustainability. The contribution of team functioning and workload to the sustainability of evidence-based mental health care warrants further study. PMID- 29793400 TI - Venous leg symptoms in patients with varicocele: A multicenter assessment study (VEIN-TURKEY study). AB - Objective The aim of this study is to evaluate chronic venous disease symptoms by using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms (VEINES-QoL/Sym) questionnaire in varicocele patients. Material and methods The study was designed as a prospective, case controlled study and conducted in four hospitals from Turkey. A total of 600 patients who admitted to urology outpatient clinic were enrolled to the study. After the exclusion of 44 patients who do not match the inclusion criteria, the remaining 556 patients were examined for the presence and grade of varicocele and subsequently examined clinically for the presence of chronic venous disease findings. Finally, patients were asked to answer the VEINES-Sym questionnaire consisting of 10 items. All patients' demographic parameters, cardiovascular risk factors, other co-morbid diseases and drug usage were noted. Results Patients were classified into two groups: varicocele (+) group ( n = 269) and varicocele (-) group ( n = 287). VEINES-Sym scores of varicocele patients were lower compared to patients without varicocele (41.41 +/- 5.21, 43.19 +/- 3.22, respectively, p < 0.001). Grades of varicocele significantly but inversely correlated with VEINES-Sym score ( r = 0, 206, p = 0.001). Logistic regression analysis revealed that presence of varicocele irrespective of grading significantly and independently associated with the presence of aching (odds ratio: 2.054, 95% confidence interval: 1.265 3.338, p = 0.004) and throbbing (odds ratio: 2.586, 95% confidence interval: 1.353-4.943, p = 0.004). Conclusion Varicocele patients have lower VEINES-Sym scores compared to patients without varicocele and this finding is inversely correlated with the degree of the varicocele. This association supports the hypothesis that there may be a systemic vessel wall abnormality in venous disease patients. Patients with symptoms related to vascular dilatation in any territory may deserve to be assessed systematically with the support of further clinical studies. PMID- 29793402 TI - Gluten in "gluten-free" food from food outlets in Melbourne: a cross-sectional study. PMID- 29793401 TI - Tweezing the cofactor preference of gymnosperm pinene synthase. AB - The cellular activities of gymnosperms monoterpene synthases are largely compromised due to their requirement for manganese, which is deficient in microbial cells. Through site-saturation mutagenesis of the residue adjacent to metal-binding glutamate, we found that pinene synthase is highly mutable at this position yet drastically alter their metal binding preference, thereby quickly improving the cellular performance in heterologous hosts. PMID- 29793403 TI - Active surveillance of men with low risk prostate cancer: evidence from the Prostate Cancer Outcomes Registry-Victoria. AB - OBJECTIVE: To characterise the practice of active surveillance (AS) for men with low risk prostate cancer by examining the characteristics of those who commence AS, the rate of adherence to accepted AS follow-up protocols over 2 years, and factors associated with good adherence. Design, setting: Retrospective cohort study; analysis of data collected from 38 sites participating in the Prostate Cancer Outcomes Registry-Victoria. PARTICIPANTS: Men diagnosed with prostate cancer between August 2008 and December 2014 aged 75 years or less at diagnosis, managed by AS for at least 2 years, and with an ISUP grade group of 3 or less (Gleason score no worse than 4 + 3 = 7). MAIN OUTCOME MEASURES: Adherence to an AS schedule consisting of at least three PSA measurements and at least one biopsy in the 2 years following diagnosis. RESULTS: Of 1635 men eligible for inclusion in the analysis, 433 (26.5%) adhered to the AS protocol. The significant predictor of adherence in the multivariate model was being diagnosed in a private hospital (v public hospital: adjusted odds ratio [aOR], 1.83; 95% CI, 1.42-2.37; P < 0.001). Significant predictors of non-adherence included being diagnosed by transurethral resection of the prostate (v transrectal ultrasound biopsy [TRUS]: OR, 0.54; 95% CI, 0.39-0.77; P < 0.001) or transperineal biopsy (v TRUS: OR, 0.32; 95% CI, 0.19-0.52; P < 0.001), and being 66 years of age or more at diagnosis (v < 55 years: OR, 0.65; 95% CI, 0.45-0.92; P = 0.015). CONCLUSION: Almost three-quarters of men who had prostate cancer with low risk of disease progression did not have follow-up investigations consistent with standard AS protocols. The clinical consequences of this shortcoming are unknown. PMID- 29793404 TI - Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial. AB - BACKGROUND: Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight >= 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000924459. PMID- 29793406 TI - A Comprehensive Analysis of Gene Expression of Xenobiotic and Endogenous Metabolizing Enzymes and Transporters in Rat Multiple Organs. AB - BACKGROUND: Drug metabolizing enzymes and transporters (DMETs) play crucial roles in drug absorption and disposition. Species differences in the interaction of compounds with DMETs may contribute to the accuracy of animal models in predicting human responses in clinical studies. Thus it is important to clarify the expression heterogeneity of DMETs between human and rat, that is commonly used as a model for evaluating drug efficacy and drug safety. METHODS: We compared the expression patterns of DMETs based on a rat RNA-seq dataset and the human Genotype-Tissue Expression (GTEx) datasets. A relatively high correlation of expression of DMETs between rat and human was observed in most organs, while a lower correlation was detected in the liver and kidney; however, a greater number of genes were variably expressed in the latter two organs. We characterized the basal expression traits of DMETs in rat in terms of organ, sex, and developmental differences. RESULTS: Co-expressed modules across organs of DMETs were identified to include potential functionally- related genes. Interestingly, most of these modules showed liver- and/or kidney-specific expression. Moreover, we identified DMETs modules that were highly correlated to sex or developmental stages. Finally, we created networks containing sex and/or developmentally-related drugs and diseases with their related DMETs to display the clinical significance of sexually dimorphic and/or developmentally- specific DMET genes. CONCLUSION: Our study provides a deeper understanding of species differences in not only DMETs but specific susceptibility to adverse drug reactions (ADRs). PMID- 29793407 TI - Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers. AB - Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. PMID- 29793408 TI - Recent Development of Small Molecule Glutaminase Inhibitors. AB - Glutaminase (GLS), which is responsible for the conversion of glutamine to glutamate, plays a vital role in up-regulating cell metabolism for tumor cell growth and is considered to be a valuable therapeutic target for cancer treatment. Based on this important function of glutaminase in cancer, several GLS inhibitors have been developed in both academia and industry. Most importantly, Calithera Biosciences Inc. is actively developing the glutaminase inhibitor CB 839 for the treatment of various cancers, and it is currently being evaluated in phase 1 and 2 clinical trials. In this review, recent efforts to develop small molecule glutaminase inhibitors that target glutamine metabolism in both preclinical and clinical studies are discussed. In particular, more emphasis is placed on CB-839 because it is the only small molecule GLS inhibitor being studied in a clinical setting. The inhibition mechanism is also discussed based on X-ray structure studies of thiadiazole derivatives present in glutaminase inhibitor BPTES. Finally, recent medicinal chemistry efforts to develop a new class of GLS inhibitors are described in the hopes of providing useful information for the next generation of GLS inhibitors. PMID- 29793409 TI - Oligopeptides for Immunotherapy Approaches in Ovarian Cancer Treatment. AB - Anti-ovarian cancer vaccines based on minimal immune determinants uniquely expressed in ovarian cancer biomarkers and absent in the human proteome appear to promise a high level of sensitivity and specificity for early ovarian cancer immunodiagnostics, immunoprevention, and immunotherapy. In this context, the present study analyses three ovarian cancer biomarkers - namely sperm surface protein Sp17, WAP four-disulfide core domain protein 2, and mullerian-inhibiting substance - and describes a methodology for constructing ovarian cancer biomarker derived oligopeptide constructs that might be useful for developing new diagnostic and immunotherapeutic approaches. PMID- 29793411 TI - Neuropharmacological screening of chiral and non-chiral phthalimidecontaining compounds in mice: in vivo and in silico experiments. AB - BACKGROUND: Thalidomide, the first synthesized phthalimide, has demonstrated sedative-hypnotic and antiepileptic effects on the central nervous system. N substituted phthalimides have an interesting chemical structure that confers important biological properties. OBJECTIVE: Non-chiral (ortho and para bis isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. METHOD: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4 aminopyridine (4-AP; 10 mg/kg). RESULTS: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. CONCLUSION: The chiral compounds exhibit a non-competitive NMDAR antagonist profile and the non chiral molecules possess selective sedative properties. The NMDAR exhibited stereoselectivity for STGLU while is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1. PMID- 29793410 TI - 4-Hydroxy-2-pyridone derivatives and the delta-pyrone isostere as novel agents against Mycobacterium smegmatis biofilm inhibitors. AB - BACKGROUND: The treatment of a bacterial infection when the bacterium is growing in a biofilm is a vexed issue. This is because the bacteria in a biofilm behaves differently compared to the individual planktonic free-form. As a result, traditional antibacterial agents lose their activity. OBJECTIVE: Presently, there are not many drugs that are effective against bacteria growing in biofilms. Based on literature reports, we have sought to develop novel derivatives of 4-hydroxy-2 pyridone as both antimycobacterial and antibiofilm agents. METHODS: The pyridone derivatives were synthesized by reacting 4-hydroxy-6-methyl-2H-pyran-2-one with appropriate amines and followed by reaction with substituted phenyl isocyanates as reported in the literature. RESULTS: Four compounds in this series significantly inhibit the growth and formation of biofilm by Mycobacterium smegmatis (mc2 155 strain) at 50 ug/ml. Further, in silico evaluation of the ADME parameters show these compounds possess good drug-like properties and have the potential to be developed both as antibiofilm and as oral antimycobacterial agents. CONCLUSION: This finding is of significance as presently very few small molecules are known to inhibit biofilm formation in mycobacteria. These compounds are unique in the sense that they are more potent against mycobacterium smegmatis in the biofilm state compared to the planktonic form. PMID- 29793412 TI - 2-Oxo-1,2,3,4-tetrahydropyrimidines Ethyl Esters as Potent beta- Glucuronidase Inhibitors: One-pot Synthesis, In vitro and In silico Studies. AB - BACKGROUND: Glucuronidation is essential for the metabolism and excretion of toxic substances. beta-Glucuronidase enzyme slows down the process of glucuronidation, and thus plays an important role in the on-set of colorectal carcinoma, and many other diseases. Inhibition of beta- glucuronidase activity is thus identified as an important approach for the treatment of several diseases. OBJECTIVE: Current study was aimed to synthesize a library of 2-oxo-1,2,3,4 tetrahydropyrimidine and to evaluate their beta-glucuronidase inhibitory activity, and their mode of enzyme inhibition. METHOD: We synthesized a series of 2-oxo-1,2,3,4-tetrahydropyrimidines 1-25 by fusing urea, ethyl acetoacetate, and a variety of aldehydes using copper nitrate trihydrate as catalyst. All synthesized compounds were evaluated for their in vitro beta-glucuronidase inhibitory activity. In addition, molecular docking studies were also performed by using MOE docking tools. RESULTS: Eighteen compounds showed inhibitory activity better than the standard D-saccharic acid 1,4-lactone, a well known beta glucuronidase inhibitor (IC50 = 45.75 +/- 2.16 uM). Compound 20 (IC50 = 1.36 +/- 0.03 uM) showed an excellent inhibitory activity, thirty-five folds superior to the standard. Docking results highlighted the role of various chemical moieties at different positions on 2- oxo-1,2,3,4-tetrahydropyrimidine skeleton in enzyme inhibitory activity. CONCLUSION: This study has identified a class of potent beta glucuronidase inhibitors with the potential to be investigated further. PMID- 29793413 TI - Synthesis and Cyototoxicities of New Azafluorenones with Apoptotic Mechanism of Action and Cell Cycle Analysis. AB - In this study, new azafluorenones, 4-(4-fluorophenyl)-2-(4-substitutedphenyl)-5H indeno[1,2-b]pyridin-5-one, I1-I8 were synthesized and chemical structures were elucidated by spectral analysis. All compounds were reported for the first time here. Compounds were tested in terms of cytotoxicity. They were found as cytotoxins/anticancer compounds. It was found that the leader compounds of the series were I5 and I8 according to SI, TS, PSE calculations. When PSE values were considered, the compound I5 having the chlorine had the highest PSE value as 126.4. Second highest PSE value of 50.5 belonged to I8, which has thiophene ring in its chemical structure. I8 as a representative compound of the series was forwarded to cell cycle analysis. I8 arrested S phase of cell cycle and lead to apoptosis by inducing PARP cleavage suggesting that at least one of the mechanism of cytotoxic action of the series was apoptosis. It was clearly demostrated that compound I8 can induce early apoptosis at a concentration of 5 MUM.The compounds I5 and I8 can be considered as leader compounds of the series with the highest SI, TS, PSE values for further studies. PMID- 29793414 TI - Oxaliplatin regulates chemotherapy induced peripheral neuropathic pain in the dorsal horn and dorsal root ganglion via the Calcineurin/NFAT pathway. AB - OBJECTIVE: The aim of this study was to investigate the mechanism of oxaliplatin in the induction of neuropathic pain as a symptom of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: The CIPN rat model was induced with a one time injection of oxaliplatin, and the paw withdrawal response was determined using von Frey filaments. The paw withdrawal threshold (PWT) value was recorded and the dorsal horn (DH) and dorsal root ganglion (DRG) tissues were collected. The mRNA and protein levels of calcineurin (CaN), nuclear factor of activated T cells (NFAT), and other relevant cytokines were determined. CaN and NFAT inhibition reagents, FK506 and 11R-VIVIT, were applied in order to investigate the functions of the CaN/NFAT pathway in the neuropathic pain processes. The levels of the downstream inflammatory cytokines, TNF-alpha and IL-1beta, were assessed by ELISA. RESULTS: The application of oxaliplatin reduced the value of PWT by 4 times on days 7(4+/-1.33)and 14(5.13+/-3.07)compared with the control group(14+/-0.91; 13.67+/-0.76). After treatment, the CaN mRNA level decreased and that of NFAT increased in DH and DRG tissues (P<0.05). However, treatment with FK506 and 11R-VIVIT decreased the value of PWT that had increased after oxaliplatin treatment. The expression of downstream cytokines related to the CaN/NFAT pathway increased, including CCR2, COX2, p-ERK, and p-P38 (all p<0.05). In addition, when the CaN/NFAT pathway was activated, the concentration of TNFalpha increased to 40pg/mg in DH tissues and 60pg/mg in DRG tissues compared with the control group, while the concentration of IL-1beta increased to over 60pg/mg in DH and DRG tissues. CONCLUSION: It was the first time to prove that oxaliplatin-induced neuropathic pain was correlated to the activation of the CaN/NFAT pathway in our rat model. This finding can provide a new direction for explore the mechanism of oxaliplatin-induced neuropathic pain. PMID- 29793415 TI - Lichen acids may be used as a potential drug for cancer therapy; by inhibiting mitochondrial thioredoxin reductase purified from rat lung. AB - BACKGROUND: Thioredoxin reductase (E.C 1.6.4.5.; TrxR) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin (Trx) in many cellular events such as DNA synthesis, DNA repair, angiogenesis, antioxidative defense, and regulating apoptosis. Although TrxR is indispensible in protecting cells against oxidative stress, the overexpression of TrxR is seen in many aggressive tumors. Therefore, targeted inhibition of TrxR has been accepted as a new approach for chemotherapy. OBJECTIVE: In this study, in vitro inhibition effect of the lichen acids (diffractaic, evernic, lobaric, lecanoric, and vulpinic acid) on mitochondrial TrxR purified from rat lung was investigated. METHOD: It was the first time the enzyme was purified from rat lungs by using 2', 5'-ADP Sepharose 4B affinity chromatography. The purity of the enzyme was checked with SDS-PAGE. In vitro inhibition effect of the lichen acids was investigated spectrophotometrically. To emphasize the importance of the obtained data, the commercial anticancer drugs cisplatin and doxorubicin were used as positive controls. RESULTS: Molecular mass of the enzyme was calculated as approximately 52.4 kDa. The enzyme was purified with a 63.6% yield, 208.3 fold, and 0.5 EU/mg proteins specific activity. The IC50 values of five lichen acids were significantly lower than IC50 values of anticancer drugs. CONCLUSION: All of the lichen acids, especially lecanoric and vulpinic acid, exhibited much stronger inhibitory effect on TrxR than the anticancer drugs cisplatin and doxorubicin. These lichen acids have pharmacological potential as effective natural antioxidants, antimicrobials, and anticancer agents. . PMID- 29793416 TI - Oleanolic Acid Ameliorates Abeta25-35 Injection-induced Memory Deficit in Alzheimer's Disease Model Rats by Maintaining Synaptic Plasticity. AB - BACKGROUND: Abnormal amyloid beta (Abeta) accumulation and deposition in the hippocampus is an essential process in Alzheimer's disease (AD). OBJECTIVE: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. METHODS: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Abeta25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured. RESULTS: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Abeta25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11+/-0.42) than that in model group (1.68+/ 0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group. CONCLUSION: The present results support that OA could ameliorate Abeta-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus. PMID- 29793417 TI - Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies. AB - BACKGROUND & OBJECTIVE: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. CONCLUSION: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies. PMID- 29793418 TI - Clinical Studies with Bismuth-213 and Actinium-225 for Hematologic Malignancies. AB - OBJECTIVES: Due to the shorter range and higher linear energy transfer of alpha particles compared to beta-particles, targeted alpha-particle therapy may produce more efficient tumor killing while sparing neighboring healthy cells. We will review the clinical studies using alpha-particle therapy for Acute Myeloid Leukemia (AML). METHODS: A series of clinical trials were conducted to assess the safety, feasibility, and anti-leukemic effects of lintuzumab, an anti-CD33 humanized monoclonal antibody, labeled with the alpha-emitters bismuth- 213 (213Bi) and actinium-225 (225Ac). RESULTS: An initial phase I study conducted in 18 patients with relapsed or refractory AML demonstrated the safety and antitumor effects of 213Bi-lintuzumab. Subsequently, 213Bi-lintuzumab produced remissions in AML patients after partial cytoreduction with cytarabine in phase I/II trial. The 46- minute half-life of 213Bi and need for an onsite generator has limited its utility. Therefore, a secondgeneration construct was developed using 225Ac, a radiometal that yields four alpha-particle emissions. A phase I trial demonstrated that a single infusion of 225Ac-lintuzumab could be given safely at doses up to 111 kBq/kg with anti-leukemic activity across all dose levels studied. In a second phase I study, 28% of older patients with untreated AML had objective responses after receiving fractionated-dose 225Aclintuzumab and low dose cytarabine. CONCLUSION: Based upon the encouraging results seen in phase I trials of 225Ac-lintuzumab, a phase II study of 225Ac-lintuzumab monotherapy for older patients with untreated AML is now in progress and is also being studied in a subset of patients with CD33-positive multiple myeloma. PMID- 29793419 TI - Role of MicroRNA in the Diagnosis and Therapy of Hepatic Metastases from Colorectal Cancer. AB - INTRODUCTION: Colorectal cancer is one of the most common malignancies in both genders and liver metastasis appear in more than 50% of patients with colorectal cancer, worsening its morbidity and mortality rates. The existing methods for the diagnosis and prognosis of colorectal cancer seem to be insufficient to predict its aggressiveness, leading to poor outcomes for the patient. OBJECTIVE: MicroRNAs are small non-coding RNAs, which interact with mRNAs in a posttranscriptional stage, and have been found to be involved in pathogenesis of cancer and its metastases. Their utility in diagnosis of colorectal liver metastasis gains ground through serum or tissue examination. METHODS: Several miRNAs are related to colorectal cancer and its liver metastasis. CONCLUSION: Some of them have oncogenic and other tumor suppressive role in the development of colorectal liver metastasis, while many of them have been proved to be correlated with the overall survival and prognosis of patients with colorectal cancer. The aim of the present review is to give a detailed account of the different miRNAs that have been described as playing a role in hepatic metastases from colorectal cancer, emphasizing their diagnostic, prognostic and therapeutic implications. PMID- 29793420 TI - Update on the Regulation of HIPK1, HIPK2 and HIPK3 Protein Kinases by microRNAs. AB - : The Homeodomain-Interacting Protein Kinases (HIPKs) HIPK1, HIPK2 and HIPK3 are Ser/Thr kinases which interact with homeobox proteins and other transcription factors, acting as transcriptional coactivators or corepressors. HIPKs contribute to regulate several biological processes, such as signal transduction, apoptosis, embryonic development, DNA-damage response, and cellular proliferation, in response to various extracellular stimuli. Recently it has emerged that, in addition to their role in cancer, fibrosis and diabetes, HIPKs may also be involved in other human diseases, including Amyotrophic Lateral Sclerosis (ALS), Rett syndrome, cerebellar diseases, and retinal vascular dysfunction. METHODS: Here, we update our previous paper concerning the regulation of HIPK proteins expression by microRNAs (miRNAs), pointing out the most recent findings about new cellular mechanisms and diseases which are affected by the interplay between HIPKs and miRNAs. CONCLUSION: Recently, it has emerged that HIPKs and their related miRNAs are involved in diabetic nephropathy, gastric cancer chemoresistance, cervical cancer progression, and recombinant protein expression in cultured cells. Interestingly, circular RNAs (circRNAs) deriving from HIPK2 and HIPK3 loci also modulate cellular proliferation and viability by sponging several miRNAs, thus emerging as new putative therapeutic targets for diabetes associated retinal vascular dysfunction, astrogliosis and cancer. PMID- 29793421 TI - Dietary aquaculture by-product hydrolysates: impact on the transcriptomic response of the intestinal mucosa of European seabass (Dicentrarchus labrax) fed low fish meal diets. AB - BACKGROUND: Aquaculture production is expected to double by 2030, and demands for aquafeeds and raw materials are expected to increase accordingly. Sustainable growth of aquaculture will require the development of highly nutritive and functional raw materials to efficiently replace fish meal. Enzymatic hydrolysis of marine and aquaculture raw materials could bring new functionalities to finished products. The aim of this study was to determine the zootechnical and transcriptomic performances of protein hydrolysates of different origins (tilapia, shrimp, and a combination of the two) in European seabass (Dicentrarchux labrax) fed a low fish meal diet (5%), for 65 days. RESULTS: Results were compared to a positive control fed with 20% of fish meal. Growth performances, anterior intestine histological organization and transcriptomic responses were monitored and analyzed. Dietary inclusion of protein hydrolysates in the low fish meal diet restored similar growth performances to those of the positive control. Inclusion of dietary shrimp hydrolysate resulted in larger villi and more goblet cells, even better than the positive control. Transcriptomic analysis of the anterior intestine showed that dietary hydrolysate inclusion restored a pattern of intestinal gene expression very close to the pattern of the positive control. However, as compared to the low fish meal diet and depending on their origin, the different hydrolysates did not modulate metabolic pathways in the same way. Dietary shrimp hydrolysate inclusion modulated more metabolic pathways related to immunity, while nutritional metabolism was more impacted by dietary tilapia hydrolysate. Interestingly, the combination of the two hydrolysates enhanced the benefits of hydrolysate inclusion in diets: more genes and metabolic pathways were regulated by the combined hydrolysates than by each hydrolysate tested independently. CONCLUSIONS: Protein hydrolysates manufactured from aquaculture by-products are promising candidates to help replace fish meal in aquaculture feeds without disrupting animal metabolism and performances. PMID- 29793422 TI - Biogeography of Coptis Salisb. (Ranunculales, Ranunculaceae, Coptidoideae), an Eastern Asian and North American genus. AB - BACKGROUND: Numerous studies have favored dispersal (colonization) over vicariance (past fragmentation) events to explain eastern Asian-North American distribution patterns. In plants, however the disjunction between eastern Asia and western North America has been rarely examined using the integration of phylogenetic, molecular dating, and biogeographical methods. Meanwhile, the biogeographic patterns within eastern Asia remain poorly understood. The goldthread genus Coptis Salisb. includes 15 species disjunctly distributed in North America, Japan, mainland China, and Taiwan. We present a dated phylogeny for Coptis under the optimal clock model and infer its historical biogeography by comparing different biogeographic models. RESULTS: The split of Coptis and Xanthorhiza Marshall occurred in the middle Miocene (ca. 15.47 Ma). Coptis started their diversification in the early late Miocene (ca. 9.55 Ma). A late Miocene vicariance event resulted in the eastern Asian and western North American disjunction in the genus. Within eastern Asia, dispersals from mainland Asia to Japan and from Japan to Taiwan occurred at ca. 4.85 Ma and at ca. 1.34 Ma, respectively. CONCLUSIONS: Our analyses provide evidence that both vicariance and dispersal events have played important roles in shaping the current distribution and endemism of Coptis, likely resulting from eustatic sea-level changes, mountain formation processes and an increasing drier and cooler climate from the middle Miocene onwards. PMID- 29793423 TI - Correction to: Identification and characterization of conserved lncRNAs in human and rat brain. AB - After publication of the original article [1], it was noticed that the Acknowledgement statement was incorrect. The original statement reads. PMID- 29793425 TI - Value of early change of serum C reactive protein combined to modified Alvarado score in the diagnosis of acute appendicitis. AB - BACKGROUND: The aim of this study is to test the diagnostic value of baseline and early change of C-reactive protein (CRP) concentrations, evaluated separately or in combination with the modified Alvarado score (MAS), in patients with clinically suspected acute appendicitis. METHODS: This is a prospective observational study including all patients presenting to the emergency department with an equivocal diagnosis of acute appendicitis. After inclusion, clinical and demographic data are recorded and blood samples were taken at baseline and 3 h after for serum CRP measurements (3 h CRP). The MAS is also calculated for all patients. The ultimate diagnosis of appendicitis was based on the histologic findings of the excised appendix in operated patients and clinical follow-up in emergency department discharged patients. Diagnostic accuracy of admission CRP, early change of CRP 3 h CRP minus admission CRP, MAS and the combination of these parameters was expressed by sensitivity, specificity, positive predictive value, negative predictive value and area under receiver operating characteristics curve. RESULTS: Five hundred patients were included from January 2010 to December 2013. Overall, 387 patients were operated the negative appendectomy rate was 8,3%. CRP concentrations were higher in patients with acute appendicitis. However, the diagnostic value of admission CRP, delta CRP and MAS was moderate with area under ROC curve respectively equal to 0.63, 0.53 and 0.6. Combining admission CRP and delta CRP values to MAS did not result in a better performance. The area under ROC curve did not exceed 0.7 with the different combinations. CONCLUSION: Early change of CRP has a moderate diagnostic value in patients with clinically suspected acute appendicitis. Combining CRP values to MAS did not improve diagnostic accuracy. PMID- 29793424 TI - Population structure and genetic diversity of 25 Russian sheep breeds based on whole-genome genotyping. AB - BACKGROUND: Russia has a diverse variety of native and locally developed sheep breeds with coarse, fine, and semi-fine wool, which inhabit different climate zones and landscapes that range from hot deserts to harsh northern areas. To date, no genome-wide information has been used to investigate the history and genetic characteristics of the extant local Russian sheep populations. To infer the population structure and genome-wide diversity of Russian sheep, 25 local breeds were genotyped with the OvineSNP50 BeadChip. Furthermore, to evaluate admixture contributions from foreign breeds in Russian sheep, a set of 58 worldwide breeds from publicly available genotypes was added to our data. RESULTS: We recorded similar observed heterozygosity (0.354-0.395) and allelic richness (1.890-1.955) levels across the analyzed breeds and they are comparable with those observed in the worldwide breeds. Recent effective population sizes estimated from linkage disequilibrium five generations ago ranged from 65 to 543. Multi-dimensional scaling, admixture, and neighbor-net analyses consistently identified a two-step subdivision of the Russian local sheep breeds. A first split clustered the Russian sheep populations according to their wool type (fine wool, semi-fine wool and coarse wool). The Dagestan Mountain and Baikal fine fleeced breeds differ from the other Merino-derived local breeds. The semi-fine wool cluster combined a breed of Romanian origin, Tsigai, with its derivative Altai Mountain, the two Romney-introgressed breeds Kuibyshev and North Caucasian, and the Lincoln-introgressed Russian longhaired breed. The coarse-wool group comprised the Nordic short-tailed Romanov, the long-fat-tailed outlier Kuchugur and two clusters of fat-tailed sheep: the Caucasian Mountain breeds and the Buubei, Karakul, Edilbai, Kalmyk and Tuva breeds. The Russian fat-tailed breeds shared co-ancestry with sheep from China and Southwestern Asia (Iran). CONCLUSIONS: In this study, we derived the genetic characteristics of the major Russian local sheep breeds, which are moderately diverse and have a strong population structure. Pooling our data with a worldwide genotyping set gave deeper insight into the history and origin of the Russian sheep populations. PMID- 29793426 TI - In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients. AB - BACKGROUND: Previous studies have shown that sugammadex resulted in the prolongation of prothrombin time and activated partial thromboplastin time. In this study, we aimed to investigate the in vitro effects of exogenous sugammadex on the coagulation variables of whole blood in healthy patients who underwent orthopedic surgery. METHODS: The effects of sugammadex on coagulations were assessed using thromboelastography (TEG) in kaolin-activated citrated blood samples taken from 14 healthy patients who underwent orthopedic surgery. The in vitro effects of three different concentrations of sugammadex (42, 193, and 301 MUg mL- 1) on the TEG profiles were compared with those of the control (0 MUg mL- 1). Previous studies indicated that these exogenous concentrations correspond to the approximate maximum plasma concentrations achieved after the administration of 4, 16, and 32 mg kg- 1 sugammadex to healthy subjects. RESULTS: Increased sugammadex concentrations were significantly associated with reduced coagulation, as evidenced by increases in reaction time (r), coagulation time, and time to maximum rate of thrombus generation (TMRTG), and decreases in the angle, maximum amplitude, and maximum rate of thrombus generation. Compared with the control, the median percentage change (interquartile range) in the TEG values of the samples treated with the highest exogenous sugammadex concentration was the greatest for r, 53% (26, 67.3%), and TMRTG, 48% (26, 59%). CONCLUSIONS: This in vitro study suggests that supratherapeutic doses of exogenous sugammadex might be associated with moderate hypocoagulation in the whole blood of healthy subjects. TRIAL REGISTRATION: identifier: UMIN000029081 , registered 11 September 2017. PMID- 29793427 TI - Falls and long-term care: a report from the care by design observational cohort study. AB - BACKGROUND: Falls and the resulting complications are common among frail older adults. We aimed to explore risk factors and potential prevention strategies for falls in elderly residents of Long-Term Care Facilities (LTCF). METHODS: This was a cross sectional study design using data from the Care by Design (CBD) study, within Nova Scotia's Capital District Health Authority. This observational time series cohort study collected data before, during and after the implementation of CBD, a new model of coordinated primary care in LTCF. Here, we analyzed data collected after the implementation of CBD (September 1, 2011- February 28, 2012). RESULTS: Falls were frequent; 56.2% of our sample of 395 residents fell at least once. In univariate analyses, male gender (p = 0.009), dementia (p = 0.005), and use of Selective Serotonin Reuptake Inhibitors or Selective Serotonin Norepinepherine Reuptake Inhibitors (SSRI/SNRI) (p = 0.084) showed statistically significant associations with having fallen. Benzodiazepine use appeared to be protective for falls (p = 0.058). In a fully adjusted multivariable linear regression model, dementia (beta coefficient 0.96, 95% CI: 0.83,1.84; p = 0.032), visual impairment (beta 0.84, 95% CI: 0.13,1.56; p = 0.021), and use of any PIMs (beta 0.34, 95% CI: 0.037,0.65; p = 0.028) were associated with increased risk of having fallen. Benzodiazepine use remained associated with reduced numbers of falls (p = 0.009), and SSRI/SNRI use was associated with increased numbers of falls (p = 0.007). Male gender was associated with increased falls in the model which excluded frailty (p = 0.022), though gender lost statistical significance once frailty was added to the model (p = 0.06). CONCLUSIONS: In our sample of LTCF residents, falls were common. Cognitive impairment, male gender, visual impairment, PIM use and use of SSRI/SNRI medications were associated with increased risk of falls, while benzodiazepine use appeared to be associated with a decreased risk of having fallen. Falls remain an important problem among LTC residents. Screening for falls during patient encounters is recommended, along with further research to identify risk factors and target interventions. PMID- 29793428 TI - De novo transcriptome assembly and positive selection analysis of an individual deep-sea fish. AB - BACKGROUND: High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives. RESULTS: We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod. CONCLUSIONS: Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies. PMID- 29793429 TI - Predictive equation of metastasis in patients with malignant ovarian epithelial tumors with the Ca-125 marker. AB - BACKGROUND: Cancer antigen (CA) 125 (CA-125) is used in ovarian cancer detection and monitoring, whose serum level has a positive correlation with tumor stage. The aim of this study was to obtain a prediction metastasis equation in a group of patients with ovarian cancer based on Ca-125. METHODS: A 2-group comparative observational study was conducted at a single oncologic institution (SOLCA) in Cuenca-Ecuador. All patients who were diagnosed with ovarian cancer between January 1996 and December 2016 were included in the current study. Group 1 (G1) patients with the I and II International Federation of Gynecology and Obstetrics (FIGO) stage and Metastasis Group (MG), with III and IV stage, were subdivided. A logistic regression equation was performed to predict metastasis based on Logarithm of serum Ca-125 levels. RESULTS: We included 85 cases in G1 and 64 patients in MG, with 47.8 +/- 15 years (G1) and 57.5 +/- 13.6 years (MG) of age (P < 0.001). Mortality in G1 was 2 cases (3.1%) and 53 cases (62.4%) in MG (P < 0.001). The CA-125 serum level was 163.5 +/- 236 in G1 and 1220.9 +/- 1940 u / ml in MG (P < 0.001). The equation to predict metastasis = (Age*0.053) + [(Logarithm Ca-125 value) * 1.078] - 8.163 with an OR 2.940 (CI 95% 2.046-4.223) P < 0.001. The sensitivity of the equation was 82.4% and the specificity was 79.7%. CONCLUSIONS: It is possible to predict the presence of metastasis in a group of patients with ovarian cancer based on Ca-125. PMID- 29793431 TI - Anaesthesia for chest wall reconstruction in a patient with Poland syndrome: CARE compliant case report and literature review. AB - BACKGROUND: Poland syndrome is a rare congenital disease, characterized by agenesis/hypoplasia of the pectoralis major muscle, usually associated with variable thoracic anomalies that needed chest wall reconstruction under general anesthesia. Anaesthetic management in Poland syndrome has scarcely been described. CASE PRESENTATION: Here, we present our anaesthetic management of Nuss procedure for chest wall correction in a 5 years old patient with Poland syndrome. We also reviewed the reports of anaesthetic management of Poland syndrome by searching Pubmed, and summarize the perioperative procedures that may warrant a safe surgery. CONCLUSIONS: Examinations before surgery, intraoperative monitoring, choice of general anesthetics and pain management after surgery should all be contemplated. PMID- 29793430 TI - New genomic data and analyses challenge the traditional vision of animal epithelium evolution. AB - BACKGROUND: The emergence of epithelia was the foundation of metazoan expansion. Epithelial tissues are a hallmark of metazoans deeply rooted in the evolution of their complex developmental morphogenesis processes. However, studies on the epithelial features of non-bilaterians are still sparse and it remains unclear whether the last common metazoan ancestor possessed a fully functional epithelial toolkit or if it was acquired later during metazoan evolution. RESULTS: To investigate the early evolution of animal epithelia, we sequenced the genome and transcriptomes of two new sponge species to characterize epithelial markers such as the E-cadherin complex and the polarity complexes for all classes (Calcarea, Demospongiae, Hexactinellida, Homoscleromorpha) of sponges (phylum Porifera) and compare them with their homologues in Placozoa and in Ctenophora. We found that Placozoa and most sponges possess orthologues of all essential genes encoding proteins characteristic of bilaterian epithelial cells, as well as their conserved interaction domains. In stark contrast, we found that ctenophores lack several major polarity complex components such as the Crumbs complex and Scribble. Furthermore, the E-cadherin ctenophore orthologue exhibits a divergent cytoplasmic domain making it unlikely to interact with its canonical cytoplasmic partners. CONCLUSIONS: These unexpected findings challenge the current evolutionary paradigm on the emergence of epithelia. Altogether, our results raise doubt on the homology of protein complexes and structures involved in cell polarity and adhesive-type junctions between Ctenophora and Bilateria epithelia. PMID- 29793432 TI - Relationship between high platelet reactivity on clopidogrel and long-term clinical outcomes after drug-eluting stents implantation (PAINT-DES): a prospective, propensity score-matched cohort study. AB - BACKGROUND: The relationship between platelet reactivity and long-term clinical outcomes remains controversial. The present prospective study was designed to explore the association between high platelet reactivity (HPR) on clopidogrel and long-term clinical outcomes following implantation of drug eluting stents (DES). METHODS: A total of 1769 consecutive patients assessed by Aggrestar (PL-11) were enrolled at our center from February 2011 to December 2017. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), defined as definite or probable stent thrombosis, spontaneous myocardial infarction, all cause death, clinically driven target vessel revascularization (TVR), or ischemic stroke. Bleeding served as the safety endpoint. Propensity score matching (PSM) analysis was performed to adjust for baseline differences in the overall cohort. RESULTS: Finally, 409 patients (23.1%) were identified with HPR on clopidogrel. At a median follow-up of 4.1 years (interquartile range, 1.8 years), the occurrence of MACCE was significantly higher in HPR on clopidogrel group than normal platelet reactivity (NPR) on clopidogrel group (15.6% vs. 5.4%, p < 0.001). After PSM, 395 paired patients were matched, and the difference in MACCE between HPR (15.7%) versus NPR (9.4%) on clopidogrel groups remained significant (P < 0.001), mainly driven by increased all cause death (5.3% vs. 1.8%, p < 0.001), and clinically driven TVR (8.1% vs. 6.3%, p = 0.019) in the HPR group. The risk of bleeding between two groups was similar. CONCLUSIONS: This prospective study confirms the relationship between HPR on clopidogrel and long term adverse cardiovascular events after coronary stenting. PMID- 29793433 TI - List randomization for eliciting HIV status and sexual behaviors in rural KwaZulu Natal, South Africa: a randomized experiment using known true values for validation. AB - BACKGROUND: List randomization (LR), a survey method intended to mitigate biases related to sensitive true/false questions, has received recent attention from researchers. However, tests of its validity are limited, with no study comparing LR-elicited results with individually known truths. We conducted a test of LR for HIV-related responses in a high HIV prevalence setting in KwaZulu-Natal. By using researcher-known HIV serostatus and HIV test refusal data, we were able to assess how LR and direct questionnaires perform against individual known truth. METHODS: Participants were recruited from the participation list from the 2016 round of the Africa Health Research Institute demographic surveillance system, oversampling individuals who were HIV positive. Participants were randomized to two study arms. In Arm A, participants were presented five true/false statements, one of which was the sensitive item, the others non-sensitive. Participants were then asked how many of the five statements they believed were true. In Arm B, participants were asked about each statement individually. LR estimates used data from both arms, while direct estimates were generated from Arm B alone. We compared elicited responses to HIV testing and serostatus data collected through the demographic surveillance system. RESULTS: We enrolled 483 participants, 262 (54%) were randomly assigned to Arm A, and 221 (46%) to Arm B. LR estimated 56% (95% CI: 40 to 72%) of the population to be HIV-negative, compared to 47% (95% CI: 39 to 54%) using direct estimates; the population-estimate of the true value was 32% (95% CI: 28 to 36%). LR estimates yielded HIV test refusal percentages of 55% (95% CI: 37 to 73%) compared to 13% (95% CI: 8 to 17%) by direct estimation, and 15% (95% CI: 12 to 18%) based on observed past behavior. CONCLUSIONS: In this context, LR performed poorly when compared to known truth, and did not improve estimates over direct questioning methods when comparing with known truth. These results may reflect difficulties in implementation or comprehension of the LR approach, which is inherently complex. Adjustments to delivery procedures may improve LR's usefulness. Further investigation of the cognitive processes of participants in answering LR surveys is warranted. PMID- 29793434 TI - Comparative transcriptome analysis of the invasive weed Mikania micrantha with its native congeners provides insights into genetic basis underlying successful invasion. AB - BACKGROUND: Mikania micrantha H.B.K. (Asteraceae) is one of the world's most invasive weeds which has been rapidly expanding in tropical Asia, including China, while its close relative M. cordata, the only Mikania species native to China, shows no harm to the local ecosystems. These two species are very similar in morphology but differ remarkably in several ecological and physiological traits, representing an ideal system for comparative analysis to investigate the genetic basis underlying invasion success. In this study, we performed RNA sequencing on the invader M. micrantha and its native congener M. cordata in China, to unravel the genetic basis underlying the strong invasiveness of M. micrantha. For a more robust comparison, another non-invasive congener M. cordifolia was also sequenced and compared. RESULTS: A total of 52,179, 55,835, and 52,983 unigenes were obtained for M. micrantha, M. cordata, and M. cordifolia, respectively. Phylogenetic analyses and divergence time dating revealed a relatively recent split between M. micrantha and M. cordata, i.e., approximately 4.81 million years ago (MYA), after their divergence with M. cordifolia (8.70 MYA). Gene ontology classifications, pathway assignments and differential expression analysis revealed higher representation or significant up regulation of genes associated with photosynthesis, energy metabolism, protein modification and stress response in M. micrantha than in M. cordata or M. cordifolia. Analysis of accelerated evolution and positive selection also suggested the importance of these related genes and processes to the adaptability and invasiveness of M. micrantha. Particularly, most (77 out of 112, i.e. 68.75%) positively selected genes found in M. micrantha could be classified into four groups, i.e., energy acquisition and utilization (10 genes), growth and reproduction (13 genes), protection and repair (34 genes), and signal transduction and expression regulation (20 genes), which may have contributed to the high adaptability of M. micrantha to various new environments and the capability to occupy a wider niche, reflected in its high invasiveness. CONCLUSIONS: We characterized the transcriptomes of the invasive species M. micrantha and its non-invasive congeners, M. cordata and M. cordifolia. A comparison of their transcriptomes provided insights into the genetic basis of the high invasiveness of M. micrantha. PMID- 29793435 TI - Exposure to lower red to far-red light ratios improve tomato tolerance to salt stress. AB - BACKGROUND: Red (R) and far-red (FR) light distinctly influence phytochrome mediated initial tomato growth and development, and more recent evidence indicates that these spectra also modulate responses to a multitude of abiotic and biotic stresses. This research investigated whether different R: FR values affect tomato growth response and salinity tolerance. Tomato seedlings were exposed to different R: FR conditions (7.4, 1.2 and 0.8) under salinity stress (100 mM NaCl), and evaluated for their growth, biochemical changes, active reactive oxygen species (ROS) and ROS scavenging enzymes, pigments, rate of photosynthesis, and chlorophyll fluorescence. RESULTS: The results showed that under conditions of salinity, tomato seedlings subjected to a lower R: FR value (0.8) significantly increased both their growth, proline content, chlorophyll content and net photosynthesis rate (Pn), while they decreased malondialdehyde (MDA) compared to the higher R: FR value (7.4). Under conditions of salinity, the lower R: FR value caused a decrease in both the superoxide anion (O2*-) and in hydrogen peroxide (H2O2) generation, an increase in the activities of superoxidase dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.7). Tomato seedlings grown under the lower R: FR value and conditions of salinity showed a higher actual quantum yield of photosynthesis (PhiPSII), electron transport rate (ETR), and photochemical quenching (qP) than those exposed to a higher R: FR, indicating overall healthier growth. However, the salinity tolerance induced at the lower R: FR condition disappeared in the tomato phyB1 mutant. CONLUSION: These results suggest that growing tomato with a lower R: FR value could improve seedlings' salinity tolerance, and phytochrome B1 play an very important role in this process. Therefore, different qualities of light can be used to efficiently develop abiotic stress tolerance in tomato cultivation. PMID- 29793436 TI - Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016. AB - BACKGROUND: Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug-drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population. METHODS: This was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged >=18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period. RESULTS: We analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period. CONCLUSIONS: Patients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug-drug interactions. PMID- 29793437 TI - Cost of illness of ischemic heart disease in Japan: a time trend and future projections. AB - BACKGROUND: Ischemic heart disease (IHD/ICD10: I20-I25) is the second leading cause of deaths in Japan and accounts for 40% of deaths due to heart diseases. This study aimed to calculate the economic burden of IHD using the cost of illness (COI) method and to identify key factors that drive the change of the economic burden of IHD. METHODS: We calculated the cost of illness (COI) every 3 years from 1996 to 2014 using governmental statistics. We then predicted the COI for every 3 years starting from 2017 up to 2029 using the fixed and variable model estimations. Only the estimated future population was used as a variable in the fixed model estimation. By contrast, variable model estimation considered the time trend of health-related indicators over the past 18 years. We derived the COI from the sum of direct and indirect costs (morbidity and mortality). RESULTS: The past estimation of COI slightly increased from 1493.8 billion yen in 1996 to 1708.3 billion yen in 2014. Future forecasts indicated that it would decrease from 1619.0 billion yen in 2017 to 1220.5 billion yen in 2029. CONCLUSION: The past estimation showed that the COI of IHD increased; in the mixed model, the COI was predicted to decrease with the continuing trend of health-related indicators. The COI of IHD in the future projection showed that, although the average age of death increased by social aging, the influence of the number of deaths and mortality cost decreased. PMID- 29793438 TI - Attitudes of U.S. Hispanic and non-Hispanic women toward congenital CMV prevention behaviors: a cross sectional study. AB - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection. The only way to protect against congenital CMV infection is to practice CMV prevention behaviors. CMV seroprevalence rates are high in Hispanic women. It is unknown whether communication strategies should differ by ethnicity. The purpose of this study was to understand differences between U.S. Hispanic and non-Hispanic women's attitudes toward CMV prevention behaviors and examine the relationship between perceived subjective norms and these attitudes. METHODS: This was a cross-sectional study using an online panel. Participants were U.S. women of childbearing age. The dependent variable was attitude toward practicing CMV prevention behaviors, specifically avoiding sharing cups, food, and utensils with a child and not kissing a child on the lips. RESULTS: Among 818 women (50% Hispanic), 16.8% of Hispanic women and 9.7% of non-Hispanic women (p = 0.002) reported familiarity with CMV. Attitudes toward CMV prevention through avoiding sharing behaviors (M Hispanic = 5.55 vs. M non-Hispanic = 5.20; p = 0.002) and not kissing a child on the lips (M Hispanic = 4.80 vs. M non-Hispanic = 4.21; p = 0.001) were positive for both ethnicities, but higher for Hispanic women. Hispanic women (M = 5.11) reported higher perceived behavioral control for avoiding kissing a child on the lips than non-Hispanic women (M = 4.63; p = 0.001). Hispanic women who were U.S. born or spoke English primarily more frequently kissed a child on the lips or engaged in sharing behaviors. Additionally, those who spoke Spanish mostly held more positive attitudes toward not kissing on the lips. Significant predictors for more positive attitudes toward CMV prevention behaviors were associated with perceived subjective norms, perceived behavioral control and pre-survey participation in risk behaviors. CONCLUSIONS: Hispanic women have more positive attitudes toward CMV prevention behaviors than non-Hispanic women, however in regression models other factors are more important predictors of positive attitudes than ethnicity. In developing strategies to encourage women to practice CMV prevention behaviors, a focus on further understanding and increasing subjective norms and perceived control over those behaviors may be warranted. PMID- 29793439 TI - KIBRA; a novel biomarker predicting recurrence free survival of breast cancer patients receiving adjuvant therapy. AB - BACKGROUND: This study was carried out to evaluate the prognostic value of KIBRA in breast cancer. METHODS: This retrospective study included breast cancer patients who sought the services of the immunohistochemistry laboratory of our unit from 2006 to 2015. Tissue microarrays were constructed and immunohistochemical staining was done to assess the KIBRA expression. The Kaplan Meier model for univariate and Cox-regression model with backward stepwise factor retention method for multivariate analyses were used. Chi square test was used to find out the associations with the established prognostic features. RESULTS: A total of 1124 patients were included in the study and KIBRA staining of 909 breast cancers were available for analysis. Cytoplasmic KIBRA expression was seen in 39.5% and nuclear expression in 44.8%. Overall KIBRA-low breast cancers accounted for 41.5%. KIBRA nuclear expression was significantly associated with positive ER and PR expression. Luminal breast cancer patients who had endocrine therapy and KIBRA-low expression had a RFS disadvantage over those who were positive for KIBRA (p = 0.02). Similarly, patients who received chemotherapy and had overall KIBRA-low expression also demonstrated a RFS disadvantage compared to those who had overall positive KIBRA expression (p = 0.018). This effect of KIBRA was independent of the other factors considered for the model. CONCLUSION: Overall low-KIBRA expression has an independent effect on the RFS and predicts the RFS outcome of luminal breast cancer patients who received endocrine therapy and breast cancer patients who received chemotherapy. PMID- 29793440 TI - Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures. AB - BACKGROUND: There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug resistance. METHODS: Using a novel microwell platform, the Microwell-mesh, we manufactured hundreds of 3D co-culture microtissues formed from PCa cells and bone marrow stromal cells. We used luciferase-expressing C42B PCa cells to enable quantification of the number of PCa cells in complex microtissue co-cultures. This strategy enabled us to quantify specific PCa cell growth and death in response to drug treatment, in different co-culture conditions. In parallel, we used Transwell migration assays to characterize PCa cell migration towards different 2D and 3D stromal cell populations. RESULTS: Our results reveal that PCa cell migration varied depending on the relative aggressiveness of the PCa cell lines, the stromal cell composition, and stromal cell 2D or 3D geometry. We found that C42B cell sensitivity to Docetaxel varied depending on culture geometry, and the presence or absence of different stromal cell populations. By contrast, the C42B cell response to Abiraterone Acetate was dependent on geometry, but not on the presence or absence of stromal cells. CONCLUSION: In summary, stromal cell composition and geometry influences PCa cell migration, growth and drug response. The Microwell-mesh and microtissues are powerful tools to study these complex 3D interactions. PMID- 29793441 TI - Dynamic transcriptome profiling towards understanding the morphogenesis and development of diverse feather in domestic duck. AB - BACKGROUND: Feathers with complex and fine structure are hallmark avian integument appendages, which have contributed significantly to the survival and breeding for birds. Here, we aimed to explore the differentiation, morphogenesis and development of diverse feathers in the domestic duck. RESULTS: Transcriptome profiles of skin owing feather follicle from two body parts at three physiological stages were constructed to understand the molecular network and excavate the candidate genes associated with the development of plumulaceous and flight feather structures. The venn analysis of differentially expressed genes (DEGs) between abdomen and wing skin tissues at three developmental stages showed that 38 genes owing identical differentially expression pattern. Together, our data suggest that feather morphological and structural diversity can be possibly related to the homeobox proteins. The key series-clusters, many candidate biological processes and genes were identified for the morphogenesis, growth and development of two feather types. Through comparing the results of developmental transcriptomes from plumulaceous and flight feather, we found that DEGs belonging to the family of WNT, FGF and BMP have certain differences; even the consistent DEGs of skin and feather follicle transcriptomes from abdomen and wing have the different expression patterns. CONCLUSIONS: Overall, this study detected many functional genes and showed differences in the molecular mechanisms of diverse feather developments. The findings in WNT, FGF and BMP, which were consistent with biological experiments, showed more possible complex modulations. A correlative role of HOX genes was also suggested but future biological verification experiments are required. This work provided valuable information for subsequent research on the morphogenesis of feathers. PMID- 29793442 TI - HLA-DQ2 and -DQ8 genotype frequency in Syrian celiac disease children: HLA-DQ relative risks evaluation. AB - BACKGROUND: Celiac disease (CD) is a common autoimmune disease in Syria which manifesting with inflammation of the small intestine and with various extra intestinal symptoms. The disease is associated with human HLA-DQ genes encoding HLA-DQ2 and DQ8 proteins. METHODS: In this study, 49 children patients of CD and 58 healthy control samples were genotyped for HLA-DQ genes using SSP-PCR technique. Relative risks for different genotypes were also evaluated. RESULTS: The DQB1*0201 allele was the most common in the patients (77.6%) followed by DQB1*0302 allele (10.2%). The highest HLA-DQB risk for CD development was found in patients carriers a DQ2.5/DQ8 genotype (1/10), followed by the patients carriers DQ2.5/DQ2.5 (1/12). CONCLUSION: The significant differences in the frequency of HLA-DQ2 and HLA-DQ8 in Syrian patients in compared with controls and relative risks predicted demonstrated the importance role of these alleles in the development of CD in Syrian children patients. PMID- 29793443 TI - Turnover intention and related factors among general practitioners in Hubei, China: a cross-sectional study. AB - BACKGROUND: High turnover among general practitioners (GPs) is a significant challenge in China's efforts to build a sustainable, effective primary care system, but little data is available to help understand and address this issue. The study was aiming at assessing the intention to leave their posts among a sample of GPs and investigating associated factors. METHODS: A cross-sectional survey was conducted between December 12, 2014 and March 10, 2015 in Hubei Province, Central China. A total of 1016 GPs (response rate, 85.67%) were investigated by using a structured self-administered questionnaire. A generalized linear regression model was used to identify the associated factors with turnover intention among GPs. RESULTS: Based on a full score of 24, the average score for GPs' turnover intention was 15.40 (SD = 3.43). 78.35% of the GPs had a moderate or higher level of turnover intention. Six hundred and thirty one (62.37%) GPs had ever been exposed to abuse of any kind (physical assault, 18.92%; verbal abuse, 54.38%; threat, 33.79%; verbal sexual harassment, 22.66%; and physical sexual harassment, 7.59%). Generalized linear regression analysis indicated that GPs who were male; who had a vocational school or higher; who had a temporary work contract; who were with lower level of job satisfaction; who reported higher scores on emotional exhaustion; who had been exposed to higher frequency of workplace violence were expressed higher intention to leave their present positions. CONCLUSION: This study shows that GP's intention to leave general practices is high in Hubei, China. In addition, the prevalence of workplace violence is high among GPs, particularly in the verbal abuse and threat. Measures such as offering permanent contract status, increasing overall job satisfaction, and improving doctor-patient relationship, are needed to moderate GP's turnover intention in order to maintain the foundation of China's three-tier health system. PMID- 29793444 TI - PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol. AB - BACKGROUND: High Dose Rate Brachytherapy (HDRB) boost is a well-established treatment for prostate cancer (PC). We describe the PROstate Multicentre External beam radioTHErapy Using Stereotactic boost (PROMETHEUS) study. Non-surgical stereotactic techniques are used to deliver similar doses to HDRB boost regimens with a dose escalation sub-study. METHODS: Eligible patients have intermediate or high risk PC. PROMETHEUS explores the safety, efficacy and feasibility of multiple Australian centres cooperating in the delivery of Prostate Stereotactic Body Radiotherapy (SBRT) technology. A SBRT boost component Target Dose (TD) of 19Gy in two fractions is to be delivered, followed by a subsequent EBRT component of 46Gy in 23 fractions. Once accrual triggers have been met, SBRT doses can be escalated in 1 Gy increments to a maximum of 22Gy in two fractions. Patient safety will also be measured with the rate of both acute and late moderate to severe Gastro-Intestinal (GI) and Genito-Urinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) toxicities as well as patient reported quality of life. Efficacy will be assessed via biochemical control after 3 years. DISCUSSION: PROMETHEUS aims to generate evidence for a non-surgical possible future alternative to HDRB boost regimens, and introduce advanced radiotherapy techniques across multiple Australian cancer centres. TRIAL REGISTRATION: The study was retrospectively registered on the ANZCTR (Australian New Zealand Clinical Trials Registry) with trial ID: ACTRN12615000223538 . PMID- 29793445 TI - Heritability of myopia and its relation with GDJ2 and RASGRF1 genes in Lithuania. AB - BACKGROUND: This study aimed to assess heritability of myopia in Lithuania and evaluate both genes GJD2 (Gap Junction Protein, Delta 2) and RASGRF1 (RAS protein specific guanine nucleotide-releasing factor 1) relation with myopia. METHODS: In this study Lithuanian twin population aged between 18 and 40 (n = 460) were examined. Single-nucleotide polymorphisms of the RASGRF1 (rs8027411) and GJD2 (rs634990) genes were assessed by real-time polymerase chain reaction method. RESULTS: Intrapair correlations for spherical equivalent in all twin pairs were significantly higher in MZ twin pairs r = 0.539 (p < 0.001, 95% CI 0.353-0.684) than in DZ twin pairs r = 0.203 (p < 0.01, 95% CI 0.0633-0.442) in myopia group. Correlations for spherical equivalent in emmetropia group were not significant in MZ twin pairs r = 0.091 (p > 0.05, 95% CI -0.215-0.381) and in DZ twin pairs r = 0.220 (p > 0.05, 95% CI -0.587-0.222). The odds ratio (95% CI) were 2.7 (1.018 7.460) for combinations of genotypes of rs634990 CC and rs8027411 GT (p = 0.046). CONCLUSIONS: Our studies have shown that the heritability of myopia makes 67.2% in Lithuania. Persons with combinations of genotypes rs634990 CC and rs8027411 GT have 2.7 times higher odds to have myopia. PMID- 29793447 TI - B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients. AB - BACKGROUND: The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC). METHODS: There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results. RESULTS: B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression. CONCLUSIONS: Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients. PMID- 29793446 TI - Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation. AB - BACKGROUND: Repurposing existing medications for antineoplastic purposes can provide a safe, cost-effective, and efficacious means to further augment available cancer care. Clinical and preclinical studies suggest a role for the beta-adrenergic antagonist (beta-blocker) propranolol in reducing rates of tumor progression in both solid and hematologic malignancies. In patients undergoing hematopoietic cell transplantation (HCT), the peri-transplant period is a time of increased activity of the beta-adrenergically-mediated stress response. METHODS: We conducted a proof-of-concept randomized controlled pilot study assessing the feasibility of propranolol administration to patients between ages 18-75 who received an autologous HCT for multiple myeloma. Feasibility was assessed by enrollment rate, tolerability, adherence, and retention. RESULTS: One hundred fifty-four patients underwent screening; 31 (20%) enrolled in other oncology trials that precluded dual trial enrollment and 9 (6%) declined to enroll in the current trial. Eighty-nine (58%) did not meet eligibility requirements and 25 (16%) were eligible; of the remaining eligible patients, all were successfully enrolled and randomized. The most common reasons for ineligibility were current beta-blocker use, age, logistics, and medical contraindications. 92% of treatment arm patients tolerated and remained on propranolol for the study duration; 1 patient discontinued due to hypotension. Adherence rate in assessable patients (n = 10) was 94%. Study retention was 100%. CONCLUSIONS: Findings show that it is feasible to recruit and treat multiple myeloma patients with propranolol during HCT, with the greatest obstacle being other competing oncology trials. These data support further studies examining propranolol and other potentially repurposed drugs in oncology populations. TRIAL REGISTRATION: This randomized controlled trial was registered at clinicaltrials.gov with the identifier NCT02420223 on April 17, 2015. PMID- 29793448 TI - Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits. AB - BACKGROUND: Topological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants. RESULTS: We used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping genes, transfer RNA genes, CTCF binding motifs, short interspersed elements, H3K4me3 and H3K27ac. We showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows' white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The linearly furthermost, and most-significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value < 0.001). CONCLUSIONS: Our results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome. PMID- 29793449 TI - Quantification of macular perfusion using optical coherence tomography angiography: repeatability and impact of an eye-tracking system. AB - BACKGROUND: The aim of the study was to evaluate the impact of integration of the eye-tracking system (ET) on the repeatability of flow density measurements using optical coherence tomography (OCT) angiography. METHODS: 20 healthy subjects were included in this study. OCT-angiography was performed using RTVue XR Avanti (Optovue Inc., Fremont, California, USA). The macula was imaged using a 3 * 3 mm scan twice with and twice without activation of the ET. Flow density data of the macular in the superficial and deep OCT angiograms were extracted and analyzed. RESULTS: The difference between the flow density (whole en face) in the first session and second session with and without ET was statistically non-significant (with ET: superficial retinal OCT angiogram: p = 0.50; deep retinal OCT angiogram: p = 0.89; without ET: superficial retinal OCT angiogram: p = 0.81; deep retinal OCT angiogram: p = 0.24). There was no significant difference in the coefficients of repeatability for measurements with and without ET in the superficial retinal OCT angiogram (adjusted p-value = 0.176), whereas the difference was significant for the deep retinal OCT angiogram (adjusted p-value = 0.008). CONCLUSIONS: Integration of the ET improved the repeatability of flow density measurements in the deep OCT angiogram; this needs to be considered when evaluating the long-term changes of flow density and when comparing data of different studies and different devices. PMID- 29793451 TI - The effect of financial incentives on patients' motivation for treatment: results of "Money for Medication," a randomised controlled trial. AB - BACKGROUND: Offering financial incentives is an effective intervention for improving adherence in patients taking antipsychotic depot medication. We assessed whether patients' motivation for treatment might be reduced after receiving financial rewards. METHODS: This study was part of Money for Medication, a multicentre, open-label, randomised controlled trial, which demonstrated the positive effects of financial incentives on antipsychotic depot compliance. Three mental healthcare institutions in Dutch secondary psychiatric care services participated. Eligible patients were aged 18-65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. For 12 months, patients were randomly assigned either to treatment as usual (control group) or to treatment as usual plus a financial reward for each depot of medication received (?30 per month if fully compliant; intervention group). They were followed up for 6 months, during which time no monetary rewards were offered for taking antipsychotic medication. To assess treatment motivation after 0, 12 and 18 months, interviews were conducted using a supplement to the Health of the Nation Outcome Scales (HoNOS) and the Treatment Entry Questionnaire (TEQ). RESULTS: Patients were randomly assigned to the intervention (n = 84) or the control group (n = 85). After 12 months, HoNOS motivation scores were available for 131 patients (78%). Ninety-one percent of the patients had no or mild motivational problems for overall treatment; over time, there were no significant differences between the intervention and control groups. TEQ data was available for a subgroup of patients (n = 61), and showed no significant differences over time between the intervention and control groups for external motivation (beta = 0.37 95% CI: -2.49 - 3.23, p = 0.799); introjected motivation (beta = - 2.39 95% CI: -6.22 - 1.44, p = 0.222); and identified motivation (beta = - 0.91 95% CI: 4.42 - 2.61, p = 0.613). After the 6-month follow-up period, results for the HoNOS and TEQ scores remained comparable. CONCLUSIONS: Offering financial incentives for taking antipsychotic depot medication does not reduce patients' motivation for treatment. TRIAL REGISTRATION: Netherlands Trial registration, number NTR2350 . PMID- 29793450 TI - Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma. AB - BACKGROUND: Knowledge about the expression and thus a role of enzymes that produce endogenous H2S - cystathionine-beta-synthase, cystathionine gamma-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient's samples, microarray and immunohistochemistry was used. METHODS: To determine the physiological importance, we used RCC4 stable cell line derived from clear cell renal cell carcinoma, where apoptosis induction by a mixture of five chemotherapeutics with/without silencing of H2S-producing enzymes was detected. Immunofluorescence was used to determine each enzyme in the cells. RESULTS: In clear cell renal cell carcinomas, expression of H2S-producing enzymes was mostly decreased compared to a part of kidney that was distal from the tumor. To evaluate a potential role of H2S-producing enzymes in the apoptosis induction, we used RCC4 stable cell line. We have found that silencing of cystathionine-beta-synthase and cystathionine gamma-lyase prevented induction of apoptosis. Immunofluorescence staining clearly showed that these enzymes were upregulated during apoptosis in RCC4 cells. CONCLUSION: Based on these results we concluded that in clear cell renal cell carcinoma, reduced expression of the H2S-producing enzymes, mainly cystathionine gamma-lyase, might contribute to a resistance to the induction of apoptosis. Increased production of the endogenous H2S, or donation from the external sources might be of a therapeutic importance in these tumors. PMID- 29793452 TI - Prevalence of psychological distress among parents of children with intellectual disabilities in Malawi. AB - BACKGROUND: Children with intellectual disabilities are common and are increasing in number as more children survive globally. In stark contrast to the 1-3% prevalence of intellectual disability in children globally (reported by WHO), studies from Malawi provide alarmingly high rates (26%). We know that the prevalence of psychological distress is as high as 50% in parents of children with intellectual disabilities in Europe and the US. No such studies have yet been conducted in Africa. This study is aimed at determining the prevalence and risk factors for psychological distress among parents of intellectually disabled children in Malawi. METHODS: This quantitative cross-sectional study was conducted in January and February 2015. One hundred and seventy mothers and fathers of children with intellectual disabilities as diagnosed by psychiatric clinical officers were randomly sampled from two selected child disability clinics. The Self-Reporting Questionnaire (SRQ) was used "as measure for psychological distress and questions on socio-demographic variables were administered to all consenting participants." Data was coded, cleaned and analyzed using STATA. RESULTS: 70/170 (41.2%) of parents of children with intellectual disabilities reported psychological distress. Univariate and multivariate analysis showed that area of residence (P < 0.05), low socio economic status (P < 0.05), knowledge of the disability of one's child (P < 0.05), low confidence in managing the disabled child (P < 0.05), increased perceived burden of care (P = 0.05), and having no sources for psychological support (P < 0.05) significantly predicted psychological distress among the parents for children with disabilities. CONCLUSION: There is huge burden of psychological distress among parents of intellectually disabled children in Malawi. Psychosocial interventions are urgently needed to support parents of children with intellectual disability in Malawi. PMID- 29793454 TI - The prevalence of smoking, second-hand smoke exposure, and knowledge of the health hazards of smoking among internal migrants in 12 provinces in China: a cross-sectional analysis. AB - BACKGROUND: Previous studies have provided inconsistent findings on smoking among migrants, and very limited data exist on their second-hand smoke exposure. This study aims to investigate internal migrants' smoking prevalence, second-hand smoke exposure among non-smokers, and knowledge of the health hazards of smoking in 12 major migrant provinces in China in 2013. METHODS: Data from the 2013 Migrant Dynamics Monitoring Survey in China published by the National Commission of Health and Family Planning was used in this study. Descriptive analysis, Chi square analysis, and sex-stratified multivariate logistic regression analysis were used to explore the determinants of current smoking and second-hand smoke exposure. RESULTS: Among 7200 migrants, 34.1% (55% male, 4% female) were current smokers. For males, factors associated with current smoking were education year (aOR = 0.95, 95% CI: 0.93-0.98), duration of stay (aOR = 1.01, 95% CI: 1.00-1.03) and occupation (aOR = 1.25, 95% CI: 1.03-1.53). For females, household registration status (aOR = 1.70, 95% CI: 1.04-2.80) was the most important factor associated with current smoking. Sixty five percent of non-smokers were exposed to second-hand smoke. Factors associated with exposure to second-hand smoke were duration of stay (aOR = 1.01, 95% CI: 1.00-1.02), divorced/widowed marital status (aOR = 0.48, 95% CI: 0.25-0.91), occupation (aOR = 1.29, 95% CI: 1.05-1.58) and the nature of employer (aOR = 0.77, 95% CI: 0.60-0.97). About 95% of participants were aware that lung cancer is one of the hazards of smoking. Non-current smokers had a better knowledge of fertility reduction and accelerated aging as hazards of smoking than current smokers (p < 0.01). Knowledge of the impact of smoking on cardiovascular diseases was relatively low compared with knowledge of other smoking-related hazards (26.1-44.3%). CONCLUSIONS: Current smoking and exposure to second-hand smoke among internal migrants in China is high. Socio-demographic characteristics and migration status were strongly associated with current smoking and second-hand smoke exposure. We recommend specifically targeted tobacco control interventions to help to address these risk factors, such as focusing on divorced/widowed women. PMID- 29793453 TI - An assessment of public health surveillance of Zika virus infection and potentially associated outcomes in Latin America. AB - BACKGROUND: We evaluated whether outbreaks of Zika virus (ZIKV) infection, newborn microcephaly, and Guillain-Barre syndrome (GBS) in Latin America may be detected through current surveillance systems, and how cases detected through surveillance may increase health care burden. METHODS: We estimated the sensitivity and specificity of surveillance case definitions using published data. We assumed a 10% ZIKV infection risk during a non-outbreak period and hypothetical increases in risk during an outbreak period. We used sensitivity and specificity estimates to correct for non-differential misclassification, and calculated a misclassification-corrected relative risk comparing both periods. To identify the smallest hypothetical increase in risk resulting in a detectable outbreak we compared the misclassification-corrected relative risk to the relative risk corresponding to the upper limit of the endemic channel (mean + 2 SD). We also estimated the proportion of false positive cases detected during the outbreak. We followed the same approach for microcephaly and GBS, but assumed the risk of ZIKV infection doubled during the outbreak, and ZIKV infection increased the risk of both diseases. RESULTS: ZIKV infection outbreaks were not detectable through non-serological surveillance. Outbreaks were detectable through serologic surveillance if infection risk increased by at least 10%, but more than 50% of all cases were false positive. Outbreaks of severe microcephaly were detected if ZIKV infection increased prevalence of this condition by at least 24.0 times. When ZIKV infection did not increase the prevalence of severe microcephaly, 34.7 to 82.5% of all cases were false positive, depending on diagnostic accuracy. GBS outbreaks were detected if ZIKV infection increased the GBS risk by at least seven times. For optimal GBS diagnosis accuracy, the proportion of false positive cases ranged from 29 to 54% and from 45 to 56% depending on the incidence of GBS mimics. CONCLUSIONS: Current surveillance systems have a low probability of detecting outbreaks of ZIKV infection, severe microcephaly, and GBS, and could result in significant increases in health care burden, due to the detection of large numbers of false positive cases. In view of these limitations, Latin American countries should consider alternative options for surveillance. PMID- 29793455 TI - Experiences with the implementation of Individual Placement and Support for people with severe mental illness: a qualitative study among stakeholders. AB - BACKGROUND: Individual Placement and Support (IPS) is an evidence-based approach to help people with severe mental illness achieve competitive employment. This article provides insight into an organizational and a financial implementation strategy for IPS in the Netherlands by exploring the perceived facilitators and barriers among participating stakeholders. The goal of this multifaceted strategy was to improve IPS implementation by improving the collaboration between all organizations involved, and realising secured IPS funding with a 'pay for performance' element. METHODS: A qualitative, explorative study among practitioners (n = 8) and decision makers (n = 7) in mental health care and vocational rehabilitation was performed using semi-structured interviews to collect rich information about the possible facilitators and barriers with regard to the organizational and financial implementation strategy for IPS. RESULTS: Important perceived facilitators were the key principles of the IPS model, regular meetings of stakeholders in mental health care and vocational rehabilitation, stakeholders' experienced ownership of IPS and collaboration, the mandate and influence of the decision makers involved and secured IPS funding. Important perceived barriers included the experienced rigidity of the IPS model fidelity scale and lack of independent fidelity reviewers, the temporary and fragmented character of the secured funding, lack of communication between decision makers and practitioners and negative attitudes and beliefs among mental health clinicians. Changes in legislation were experienced as a facilitator as well as a barrier. CONCLUSIONS: The results of this study suggest that the collaboration and IPS funding were experienced as improved by applying an organizational and a financial implementation strategy. However, considerable effort is still necessary to overcome the remaining barriers identified and to make the implementation of IPS a success in practice. PMID- 29793456 TI - Prevalence of patellofemoral pain and knee pain in the general population of Chinese young adults: a community-based questionnaire survey. AB - BACKGROUND: Previous studies that have described the prevalence of patellofemoral pain (PFP) have been limited to samples of military personnel or sporting populations, and convincing data in the general Chinese population are lacking. The present study defined the prevalence of PFP and knee pain in the general population of Chinese young adults and evaluated whether gender, age, or body mass index (BMI) were associated with PFP. METHODS: An anonymous online questionnaire survey was open to the general public in China. A self-report questionnaire was used to specifically identify PFP. The population aged 18-40 years was enrolled in the study and completed the questionnaire. The prevalence of PFP and knee pain in the overall sample and in subgroups stratified by sex, age, and BMI was estimated. Logistic regression analysis was conducted to determine if there was a significant association between PFP and sex, age, or BMI. RESULTS: A total of 1153 participants were enrolled in the study. The prevalence of PFP in the overall sample and among the male and female participants was 20.7, 20.3, and 21.2%, respectively. The prevalence of the knee pain in the overall sample and among the male and female participants was 35.6, 38.2, and 33.7%, respectively. The prevalence of PFP in the subgroups stratified by age and BMI did not differ significantly between the groups. Gender, age, and BMI did not have significant associations with the prevalence of PFP. CONCLUSION: PFP is common in the general Chinese population. Clinicians should direct more attention toward the early diagnosis of and interventions for PFP. PMID- 29793457 TI - Decolonization potential of 0.02% polyhexanide irrigation solution in urethral catheters under practice-like in vitro conditions. AB - BACKGROUND: Long-term use of indwelling urethral catheters is associated with high risk of urinary tract infection (UTI) and blockage, which may in turn cause significant morbidity and reduce the life of the catheter. A 0.02% polyhexanide irrigation solution has been developed for routine mechanical rinsing together with bacterial decolonization of suprapubic and indwelling urethral catheters. METHODS: Using a practice-like in vitro assay and standard silicon catheters, artificially contaminated with clinically relevant bacteria, experiments were carried out to evaluate the bacterial decolonization potential of polyhexanide vs. 1) no intervention (standard approach) and 2) irrigation with a saline (NaCl 0.9%) solution. Swabbing and irrigation was used to extract the bacteria. RESULTS: Irrigation with polyhexanide reduced the microbial population vs. the control catheters by a factor of 1.64 log10 (swab extraction) and by a factor of 2.56 log10 (membrane filtration). The difference in mean microbial counts between the two groups (0.90) was statistically significant in favor of polyhexanide when the liquid extraction method was used (p = 0.034). The difference between the two groups using the swab extraction method did not reach statistical significance. CONCLUSIONS: The saline and polyhexanide solutions are able to reduce bacterial load of catheters, which shows a combined mechanical and antimicrobial effect. Further research is required to evaluate the long-term tolerability and efficacy of polyhexanide in clinical practice. PMID- 29793458 TI - Human osteochondritis dissecans fragment-derived chondrocyte characteristics ex vivo, after monolayer expansion-induced de-differentiation, and after re differentiation in alginate bead culture. AB - BACKGROUND: Autologous chondrocyte implantation (ACI) is a therapy for articular cartilage and osteochondral lesions that relies on notch- or trochlea-derived primary chondrocytes. An alternative cell source for ACI could be osteochondritis dissecans (OCD) fragment-derived chondrocytes. Assessing the potential of these cells, we investigated their characteristics ex vivo and after monolayer expansion, as monolayer expansion is an integral step of ACI. However, as monolayer expansion can induce de-differentiation, we asked whether monolayer induced de-differentiation can be reverted through successive alginate bead culture. METHODS: Chondrocytes were isolated from the OCD fragments of 15 patient knees with ICRS grades 3-4 lesions for ex vivo analyses, primary alginate bead culture, monolayer expansion, and alginate bead culture following monolayer expansion for attempting re-differentiation. We determined yield, viability, and the mRNA expression of aggrecan and type I, II, and X collagen. RESULTS: OCD fragment-derived chondrocyte isolation yielded high numbers of viable cells with a low type I:II collagen expression ratio (< 1) and a relatively high aggrecan and type II and X collagen mRNA expression, indicating chondrogenic and hypertrophic characteristics. As expected, monolayer expansion induced de differentiation. Alginate bead culture of monolayer-expanded cells significantly improved the expression profile of all genes investigated, being most successful in decreasing the hypertrophy marker type X collagen to 1.5% of its ex vivo value. However, the chondrogenic phenotype was not fully restored, as the collagen type I:II expression ratio decreased significantly but remained > 1. CONCLUSION: OCD fragment derived human chondrocytes may hold not yet utilized clinical potential for cartilage repair. PMID- 29793459 TI - Morphology of intervertebral disc ruptures evaluated by vacuum phenomenon using multi-detector computed tomography: association with lumbar disc degeneration and canal stenosis. AB - BACKGROUND: The progression of intervertebral disc (IVD) degeneration leads to rupture within IVD tissues. The location and appearance of areas of gaseous radiolucency in the IVD, known as vacuum phenomena (VPs), are considered to indirectly indicate the position and extent of IVD rupture. The clinical significance of VPs in degenerated IVDs is not fully understood. The purpose of this study is to assess and classify the morphology of IVD ruptures by the presence of intradiscal VPs, and to examine the association between morphological VP-positive IVD ruptures and degenerative lumbar diseases. METHODS: IVD rupture was evaluated by the presence of VPs using computed tomography (CT) imaging. VP shape (spot, linear, island) was classified using sagittal imaging, and VP distribution (A-N: anterior AF-NP; N: NP only; N-P: NP-posterior AF; A-N-P: anterior and posterior AF-NP) was classified using axial imaging. The disc height index (DHI) was calculated from lateral radiographs. Disc degeneration and lumbar spinal stenosis were evaluated by MRI grade. RESULTS: In the VP shape analysis, the island type was the most common, followed by linear and spot types. In the VP distribution analysis, A-N was the most common group, followed by N, N-P and A-N P. Intra- and inter-observer reliabilities were statistically sufficient to classify different rupture shapes and distributions. The DHI tended to be lower in discs that contained VPs, especially in the anterior AF area. The shape and distribution of intradiscal VPs were significantly associated with the degree of disc degeneration and lumbar spinal stenosis graded by MRI. Discs with VPs extending from the NP into the anterior and/or posterior AF had a significantly higher proportion of advanced disc degeneration (Pfirrmann's classification: grades IV and V). CONCLUSIONS: This is the first study to analyze the morphology of IVD rupture evaluated by the presence of intradiscal VPs using CT imaging. This classification can comprehensively present the shape and axial distribution of VPs within IVDs. Intradiscal VPs are associated with the progression of disc degeneration and lumbar spinal stenosis. PMID- 29793460 TI - Effect of altering breathing frequency on maximum voluntary ventilation in healthy adults. AB - BACKGROUND: Compared to other pulmonary function tests, there is a lack of standardization regarding how a maximum voluntary ventilation (MVV) maneuver is performed. Specifically, little is known about the variation in breathing frequency (fR) and its potential impact on the accuracy of test results. This study examines the effect of several preselected values for fR and one self selected fR (fRself) on MVV. METHODS: Ten participants performed MVV maneuvers at various fR values, ranging from 50 to 130 breaths.min- 1 in 10 breaths.min- 1 intervals and at one fRself. Three identical trials with 2-min rest periods were conducted at each fR, and the sequence in which fR was tested was randomized. Ventilation and related parameters were measured directly by gas exchange analysis via a metabolic measurement system. RESULTS: A third-order polynomial regression analysis showed that MVV = - 0.0001(fR)3 + 0.0258(fR)2-1.38(fR) + 96.9 at preselected fR and increased up to approximately 100 breaths.min- 1 (r2 = 0.982, P < 0.001). Paired t-tests indicated that average MVV values obtained at all preselected fR values, but not fRself, were significantly lower than the average maximum value across all participants. A linear regression analysis revealed that tidal volume (VT) = - 2.63(MVV) + 300.4 at preselected fR (r2 = 0.846, P < 0.001); however, this inverse relationship between VT and MVV did not remain true for the self-selected fR. The VT obtained at this fR (90.9 +/- 19.1% of maximum) was significantly greater than the VT associated with the most similar MVV value (at a preselected fR of 100 breaths.min- 1, 62.0 +/- 10.4% of maximum; 95% confidence interval of difference: (17.5, 40.4%), P < 0.001). CONCLUSIONS: This study demonstrates the shortcomings of the current lack of standardization in MVV testing and establishes data-driven recommendations for optimal fR. The true MVV was obtained with a self-selected fR (mean +/- SD: 69.9 +/- 22.3 breaths.min- 1) or within a preselected fR range of 110-120 breaths.min- 1. Until a comprehensive reference equation is established, it is advised that MVV be measured directly using these guidelines. If an individual is unable to perform or performs the maneuver poorly at a self-selected fR, ventilating within a mandated fR range of 110-120 breaths.min- 1 may also be acceptable. PMID- 29793461 TI - Treatment of displaced transverse fractures of the patella: modified tension band wiring technique with or without augmented circumferential cerclage wire fixation. AB - BACKGROUND: Displaced transverse fractures of the body of the patella are usually associated with disruption of extensor mechanism and should be fixed surgically. The most common method is a tension band wiring (TBW) technique. Some surgeons concurrently employ an augmented circumferential cerclage wiring (ACCW) technique to help fracture stabilization and aid in fracture healing; however, its role and effect on the treatment outcomes is unclear. METHODS: We performed a STROBE compliant retrospective observational cohort study on all cases of acute closed patella fracture that were treated at our institution between 2006 and 2012. Of 185 episodes, 72 (38.9%) were eligible for this study according to our inclusion/exclusion criteria. We classified these subjects with AO/OTA type 34 C1.1 or 34-C2 lesions into two groups for analyses: fractures treated with modified TBW and ACCW (group 1, n = 27) and those treated with modified TBW alone (group 2, n = 45). Plain radiographs were used to evaluate radiographic outcomes and the effect of potential risk factors on fixation failure was analyzed by subgroup comparisons. RESULTS: Our results revealed that there were no significant differences in the rates of fixation failure (P = 0.620), nonunion (P = 0.620), and revision surgery (P = 0.620) between the groups. Although not statistically significant, there was a trend towards a positive risk association between fixation failure and age distribution > 60 years (10.0% vs. 0.0%, P = 0.124; OR = 8.0, P = 0.168) and > 70 years (9.4% vs. 2.5%, P = 0.321; OR = 4.0, P = 0.237) and the superficial level of the K-wires (12.0% vs. 1.5%, P = 0.117; OR = 6.3, P = 0.121). Regarding those modified TBW patients concurrently treated with an ACCW, the potential risk association between fixation failure and the superficial level of the K-wire was prone to increase further (28.6% vs. 0.0%, P = 0.060; OR = 18.6, P = 0.071). CONCLUSIONS: Concurrent application of an ACCW might be needless and not efficacious to help fracture stabilization and healing in patients having been treated with modified TBW for displaced transverse fractures of the body of the patella. Adherence to correct surgical technique such as putting the K-wires at the proper level and securing control of the both ends of the K-wires may be more important and help in improving outcomes. PMID- 29793462 TI - Eliminating the high abortion related complications and deaths in Cameroon: the restrictive legal atmosphere on abortions is no acceptable excuse. AB - BACKGROUND: The abortion law in Cameroon is highly restrictive. The law permits induced abortions only when the woman's life is at risk, to preserve her physical and mental health, and on grounds of rape or incest. Unsafe abortions remain rampant with however rare reported cases of persecution, even when these abortions are proven to have been carried out illegally. DISCUSSION: Available public health interventions are cheap and feasible (Misoprostol and Manual Vacuum Aspiration in post abortion care, modern contraception, post-abortion counseling), and must be implemented to reduce unacceptably high maternal mortality rates in the country which still stand at as high as 596/100.000. Changes in the legal status of abortions might take a long time to come by. Albeit, advocacy efforts must be reinforced to render the law more liberal to permit women to seek safe abortion services. The frequency of abortions, generally clandestine, in this restrictive legal atmosphere has adverse economic, health and social justice implications. CONCLUSION: We argue that a non-optimal or restrictive legal atmosphere is not an acceptable excuse to justify these high maternal deaths resulting from unsafe abortions, especially in Cameroon where unsafe abortions remain rampant. Implementing currently available, cheap and effective evidence based practice guidelines are possible in the country. Expansion and use of Manual Vacuum Aspiration kits in health care facilities, post-abortion misoprostol and carefully considering the content of post abortion counseling packages deserve keen attention. More large scale qualitative and quantitative studies nationwide to identify and act on context specific barriers to contraception use and abortion related stigma are urgently needed. PMID- 29793463 TI - Cartilage calcification of the ankle joint is associated with osteoarthritis in the general population. AB - BACKGROUND: Cartilage calcification (CC) is associated with osteoarthritis (OA) in weight-bearing joints, such as the hip and the knee. However, little is known about the impact of CC and degeneration on other weight-bearing joints, especially as it relates to the occurrence of OA in the ankles. The goal of this study is to analyse the prevalence of ankle joint cartilage calcification (AJ CC) and to determine its correlation with factors such as histological OA grade, age and BMI in the general population. METHODS: CC of the distal tibia and talus in 160 ankle joints obtained from 80 donors (mean age 62.4 years, 34 females, 46 males) was qualitatively and quantitatively analysed using high-resolution digital contact radiography (DCR). Correlations with factors, such as the joint's histological OA grade (OARSI score), donor's age and BMI, were investigated. RESULTS: The prevalence of AJ CC was 51.3% (95% CI [0.40, 0.63]), independent of gender (p = 0.18) and/or the joint's side (p = 0.82). CC of the distal tibia was detected in 35.0% (28/80) (95% CI [0.25, 0.47]) and talar CC in 47.5% (38/80) (95% CI [0.36, 0.59]) of all cases. Significant correlations were noted between the mean amount of tibial and talar CC (r = 0.59, p = 0.002), as well as between the mean amount of CC observed in one ankle joint with that of the contralateral side (r = 0.52, p = 0.02). Furthermore, although the amount of AJ CC observed in the distal tibia and talus correlated with the histological OA-grade of the joint (r = 0.70, p < 0.001 and r = 0.72, p < 0.001, respectively), no such correlation was seen in the general population with relation to age (p = 0.32 and p = 0.49) or BMI (p = 0.51 and p = 0.87). CONCLUSION: The prevalence of AJ CC in the general population is much higher than expected. The relationship between the amount of AJ CC and OA, independent of the donors' age and BMI, indicates that CC may play a causative role in the development of OA in ankles. PMID- 29793465 TI - Selected psychiatric problems among college students in two Arab countries: comparison with the USA. AB - BACKGROUND: Psychiatric problems among college students on USA campuses are common. Little is known about similar problems in developing countries, particularly the Arab region. The goal of this study was to assess the frequency of selected psychiatric problems among college students in two Arab countries: Qatar and Lebanon, and to compare them to the USA. METHODS: The Healthy Minds Study, an online confidential survey of common psychiatric symptoms designed for college campuses was used. We used the Patient Health Questionnaire-9 (PHQ-9) to screen for major depression, the Generalized Anxiety Disorder-7 (GAD-7) to screen for generalized anxiety and the SCOFF questionnaire to screen for eating disorders. Comparisons were made using ANOVA, Chi-Square tests and logistic regressions. RESULTS: A total of 1841 students participated in the study. The rates of depression (PHQ-9 >= 12), generalized anxiety (GAD-7 >= 10) and eating disorders (SCOFF>=3) at the combined Arab universities were 34.6, 36.1 and 20.4% respectively. The corresponding rates in the USA were: 12.8, 15.9 and 6.8% (p < 0.001 for all measures). The impact of psychiatric problems on functioning in general and academic performance in particular was more severe in the Arab countries compared to the USA (p < 0.001). Independent predictors of psychiatric problems in general included location, female gender, financial difficulties and poor grades. Being religious had a protective association with mental health. CONCLUSION: The rates of depression, anxiety and eating disorders were significantly higher among college students in Qatar and Lebanon compared to the USA. Additional research is needed to determine whether these results reflect methodological limitations or true differences in psychopathology across these populations. If replicated, the results indicate that the psychiatric problems on college campuses in the USA are a microcosm of a global problem that needs global solutions. PMID- 29793464 TI - A retrospective comparative study of arthroscopic fixation in acute Rockwood type IV acromioclavicular joint dislocation: single versus double paired Endobutton technique. AB - BACKGROUND: Rockwood type IV acromioclavicular joint (ACJ) dislocation is a trauma usually needs surgical treatment. Paired EndoButton technique (PET) is used in treating such condition. However, the effect of using different types of PET (single versus double PET) for fixation remains controversial. This study aims to evaluate and compare the efficacy of single and double PET and to provide a suitable option for the surgeons. METHODS: We retrospectively reviewed the charts of patients with acute Rockwood type IV ACJ dislocation who had undergone arthroscopic fixation using single or double PET fixation between March 2009 and March 2015. Seventy-eight consecutive patients identified from chart review were picked and were divided into the single and double PET group with 39 cases in each group. The indexes of visual analog scale score (VAS) for pain, the radiographs of the affected shoulder at different time points of the follow-up, the time of return to activities and sports, the constant functional score, and the Karlsson acromioclavicular joint (ACJ) score, were assessed in a minimum of 2 years postoperation. RESULTS: The average coracoclavicular (CC) and acromioclavicular (AC) distances of the affected joints in the double PET group were significantly smaller than those of the single PET group 2 years postoperation (P < 0.05). The average AC and CC distances in the healthy shoulder joints were significantly smaller than those of the affected joints in the single PET group (P < 0.05); however, these values were not significantly different from those of the affected joints in the double PET group (P > 0.05). The mean VAS pain score was not significantly different, while significant difference was found for the number and times of cases return to activities and sports, constant functional score, and Karlsson ACJ score (P < 0.05) between the two groups. Therefore, the double PET group has better outcome than the single PET group. Complications including redislocation, button slippage, erosion, or AC joint instability occurred in the single PET group, while the complication in the double PET group was rare. CONCLUSIONS: Compared with the single PET, the double PET group achieved better outcome with less complications in arthroscopically treating acute Rockwood type IV ACJ dislocation. PMID- 29793466 TI - The diagnosis and arthroscopic treatment of angioleiomyoma presenting loose body in the knee joint: two case reports. AB - BACKGROUND: Angioleiomyoma is a very rare benign solitary soft tissue neoplasm originating from smooth muscle layer of blood vessels. The tumor is usually located in the subcutis or the superficial fasciae, but less often in the deep fasciae, especially rare in the knee joint cavity. Diagnosis is frequently delayed or misdiagnosed as loose body or anterior knee pain because of its rare occurrence and poor awareness of physicians. Few studies have presented intra articular angioleiomyoma and such cases become rarer and more difficult to diagnose when it presents as loose body. CASE PRESENTATION: Two patients, a middle-aged man and an old woman, presented to our outpatient clinic with persistent anterior knee pain and both of them suffered from a solitary mass in the right knee that had slowly enlarged. One of two patients showed negative in the routine radiographic imaging and the other showed a "loose body" beside the lateral femoral condyle in the knee. MRI showed both a well-demarcated intra articular mass of isointense signal to muscle on T1-weighted images and heterogeneous intensity on T2-weighted images. Their tumors were excised under arthroscopy finally, with the pathological results revealed vascular leiomyomas. They both recovered well with pain free after operation and no signs of recurrence were seen at the 7-year follow-up. CONCLUSIONS: This case report illustrates the atypical locations of angioleiomyoma in the knee joint should arouse our attention and be included in the differential diagnosis of nodular lesions mimicking loose bodies. PMID- 29793467 TI - A 12-month follow-up of a mobile-based (mHealth) obesity prevention intervention in pre-school children: the MINISTOP randomized controlled trial. AB - BACKGROUND: To date, few mobile health (mHealth) interventions aimed at changing lifestyle behaviors have measured long term effectiveness. At the 6-month follow up the MINISTOP trial found a statistically significant intervention effect for a composite score comprised of fat mass index (FMI) as well as dietary and physical activity variables; however, no intervention effect was observed for FMI. Therefore, the aim of this study was to investigate if the MINISTOP intervention 12-months after baseline measurements: (i) improved FMI and (ii) had a maintained effect on a composite score comprised of FMI and dietary and physical activity variables. METHODS: A two-arm parallel randomized controlled trial was conducted in 315 healthy 4.5 year old children between January 2014 and October 2015. Parents' of the participating children either received the MINISTOP intervention or a basic pamphlet on dietary and physical activity behaviors (control group). After 6 months, participants did not have access to the intervention content and were measured again 6 months later (i.e. the 12-month follow-up). The Wilcoxon rank-sum test was then used to examine differences between the groups. RESULTS: At the 12-month follow-up, no statistically significant difference was observed between the intervention and control groups for FMI (p = 0.57) and no maintained effect for the change in composite score was observed (mean +/- standard deviation for the intervention and control group: + 0.53 +/- 1.49 units and + 0.35 +/- 1.27 units respectively, p = 0.25 between groups). CONCLUSIONS: The intervention effect observed at the 6-month follow-up on the composite score was not maintained at the 12-month follow-up, with no effect on FMI being observed at either follow-up. Future studies using mHealth are needed to investigate how changes in obesity related markers in young children can be maintained over longer time periods. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02021786 ; 20 Dec 2013). PMID- 29793468 TI - Increasing prevalence of overweight and obesity in Yi farmers and migrants from 2007 to 2015 in China: the Yi migrant study. AB - BACKGROUND: With the social development and lifestyle transition, increasing trends of overweight and obesity prevalence are commonly reported worldwide. Data focusing on overweight and obesity trends in rural residents and rural-to-urban migrants in China are limited. This study aims to assess the changes and related factors of overweight and obesity in Yi farmers and migrants in southwest China from 2007 to 2015, and to assess the disparities in prevalence changes. METHODS: Pseudo-panel data was obtained from two cross-sectional studies conducted in Sichuan province, southwest China in 2007 and 2015. Standardized prevalence of overweight and obesity were evaluated by direct method using the 2010 national census population as the standard. Prevalence differences of overweight and obesity were calculated in each group and compared between groups to evaluate the disparity in prevalence changes. Generalized linear mixed model was performed to determine factors related to overweight/obesity. RESULTS: Standardized prevalence of overweight increased in both groups (from 5.54 to 16.65% in Yi farmers, from 27.91 to 33.61% in Yi migrants). Standardized prevalence of obesity increased only in Yi farmers (from 0.37 to 3.13%). Prevalence difference of overweight in Yi farmers was higher than that in Yi migrants (11.11 vs. 5.70), but prevalence differences of obesity were not significantly different between Yi farmers and migrants. CONCLUSIONS: Prevalence of overweight and obesity in Yi farmers, and prevalence of overweight in Yi migrants increased from 2007 to 2015. Yi farmers were developing overweight at a greater pace than migrants. More attention should be paid to spread health knowledge and encourage healthy lifestyle in Yi people, especially Yi farmers. PMID- 29793469 TI - Whose job? The staffing of advance care planning support in twelve international healthcare organizations: a qualitative interview study. AB - BACKGROUND: ACP involving a facilitated conversation with a health or care professional is more effective than document completion alone. In policy, there is an expectation that health and care professionals will provide ACP support, commonly within their existing roles. However, the potential contributions of different professionals are outlined only broadly in policy and guidance. Research on opportunities and barriers for involving different professionals in providing ACP support, and feasible models for doing so, is currently lacking. METHODS: We identified twelve healthcare organizations aiming to offer system wide ACP support in the United States, Canada, Australia and New Zealand. In each, we conducted an average 13 in-depth interviews with senior managers, ACP leads, dedicated ACP facilitators, physicians, nurses, social workers and other clinical and non-clinical staff. Interviews were analyzed thematically using NVivo software. RESULTS: Organizations emphasized leadership for ACP support, including strategic support from senior managers and intensive day-to-day support from ACP leads, to support staff to deliver ACP support within their existing roles. Over-reliance on dedicated facilitators was not considered sustainable or scalable. We found many professionals, from all backgrounds, providing ACP support. However, there remained barriers, particularly for facilitating ACP conversations. A significant barrier for all professionals was lack of time. Physicians sometimes had poor communication skills, misunderstood medico-legal aspects and tended to have conversations of limited scope late in the disease trajectory. However, they could also have concerns about the appropriateness of ACP conversations conducted by others. Social workers had good facilitation skills and understood legal aspects but needed more clinical support than nurses. While ACP support provided alongside and as part of other care was common, ACP conversations in this context could easily get squeezed out or become fragmented. Referrals to other professionals could be insecure. Team-based models involving a physician and a nurse or social worker were considered cost-effective and supportive of good quality care but could require some additional resource. CONCLUSIONS: Effective staffing of ACP support is likely to require intensive local leadership, attention to physician concerns while avoiding an entirely physician-led approach, some additional resource and team-based frameworks, including in evolving models of care for chronic illness and end of life. PMID- 29793470 TI - Universal health coverage in the context of population ageing: What determines health insurance enrolment in rural Ghana? AB - BACKGROUND: Population ageing presents considerable challenges for the attainment of universal health coverage (UHC), especially in countries where such coverage is still in its infancy. Ghana presents an important case study on the effectiveness of policies aimed at achieving UHC in the context of population ageing in low and middle-income countries. It has witnessed a profound recent demographic transition, including a large increase in the number of older adults, which coincided with the development and implementation of a National Health Insurance Scheme (NHIS), designed to help achieve UHC. The objective of this paper is to examine the community, household and individual level determinants of NHIS enrolment among older adults aged 50-69 and 70 plus. The latter are exempt from NHIS premium payments. METHODS: Using the Ghanaian Living Standards Survey from 2012 to 2013, determinants of NHIS enrolment for individuals aged 50-69 and 70 plus living in rural Ghana are examined through the application of multilevel regression analysis. RESULTS: Previous studies have mainly focused on the enrolment of young and middle aged adults and considered mainly demographic and socio-economic factors. The novel inclusion of spatial barriers within this analysis demonstrates that levels of NHIS enrolment are determined in part by the community provision of healthcare facilities. In addition, the findings imply that insurance enrolment increases with household expenditure even for those aged 70 plus who are exempt from the NHIS premium payment. CONCLUSION: Adequate and appropriate infrastructure as well as health insurance is vital to ensure movement to UHC in low and middle income countries. Overall, the results confirm that there remain significant inequalities in enrolment by expenditure quintile that future policy reform will need to address. PMID- 29793471 TI - Surgical informed consent in obstetric and gynecologic surgeries: experience from a comprehensive teaching hospital in Southern Ethiopia. AB - BACKGROUND: Surgical Informed Consent (SIC) has long been recognized as an important component of modern medicine. The ultimate goals of SIC are to improve clients' understanding of the intended procedure, increase client satisfaction, maintain trust between clients and health providers, and ultimately minimize litigation issues related to surgical procedures. The purpose of the current study is to assess the comprehensiveness of the SIC process for women undergoing obstetric and gynecologic surgeries. METHODS: A hospital-based cross-sectional study was undertaken at Hawassa University Comprehensive Specialized Hospital (HUCSH) in November and December, 2016. A total of 230 women who underwent obstetric and/or gynecologic surgeries were interviewed immediately after their hospital discharge to assess their experience of the SIC process. Thirteen components of SIC were used based on international recommendations, including the Royal College of Surgeon's standards of informed consent practices for surgical procedures. Descriptive summaries are presented in tables and figures. RESULTS: Forty percent of respondents were aged between 25 and 29 years. Nearly a quarter (22.6%) had no formal education. More than half (54.3%) of respondents had undergone an emergency surgical procedure. Only 18.4% of respondents reported that the surgeon performing the operation had offered SIC, while 36.6% of respondents could not recall who had offered SIC. All except one respondent provided written consent to undergo a surgical procedure. However, 8.3% of respondents received SIC service while already on the operation table for their procedure. Only 73.9% of respondents were informed about the availability (or lack thereof) of alternative treatment options. Additionally, a majority of respondents were not informed about the type of anesthesia to be used (88.3%) and related complications (87.4%). Only 54.2% of respondents reported that they had been offered at least six of the 13 SIC components used by the investigators. CONCLUSIONS: There is gap in the provision of comprehensive and standardized pre operative counseling for obstetric and gynecologic surgeries in the study hospital. This has a detrimental effect on the overall quality of care clients receive, specifically in terms of client expectations and information needs. PMID- 29793472 TI - Realization of the right to adequate food and the nutritional status of land evictees: a case for mothers/caregivers and their children in rural Central Uganda. AB - BACKGROUND: In developing countries like Uganda, the human right to adequate food (RtAF) is inextricably linked to access to land for households to feed themselves directly through production or means for its procurement. Whether RtAF is enjoyed among Ugandan land evictees, is unknown. We therefore explored this among land evictees (rights-holders) in Wakiso and Mpigi districts in rural Central Uganda. We assessed food accessibility and related coping strategies, diet quality and nutritional status of children 6-59 months old, and their caregivers. Effectiveness of the complaint and redress mechanisms in addressing RtAF violations was also explored. METHODS: In this cross-sectional study, quantitative data was collected using a structured questionnaire, with food security and nutritional assessment methods from a total of 215 land evictees including 187 children aged 6-59 months. Qualitative data was collected by reviewing selected national and international documents on the RtAF and key informant interviews with 15 purposively sampled duty-bearers. These included individuals or representatives of the Uganda Human Rights Commission, Resident District Commissioner, Sub-county Chiefs, and local Council leaders. RESULTS: We found that 78% of land evictees had insufficient access to food while 69.4% had consumed a less diversified diet. A majority of evictees (85.2%) relied on borrowing food or help from others to cope with food shortages. Of the 187 children assessed, 9.6% were wasted, 18.2% were underweight and 34.2% were stunted. Small, but significant associations, were found between food accessibility, diet quality, food insecurity coping strategies; and the nutritional status of evictees. We observed that administrative, quasi-judicial and judicial mechanisms to provide adequate legal remedies regarding violations of the RtAF among evictees in Uganda are in place, but not effective in doing so. CONCLUSION: Land eviction without adequate legal remedies is a contributor to food insecurity and undernutrition in rural Central Uganda. It is essential that the Government strengthens and enforces the policy and legal environment to ensure adequate and timely compensation of evictees in order to reduce their vulnerability to food insecurity. PMID- 29793474 TI - Are Michigan State University medical school (MSU-CHM) alumni more likely to practice in the region of their graduate medical education primary care program compared to non-MSU-CHM alumni? AB - BACKGROUND: Over the past 10 years, three new MD schools have been created in the state of Michigan, while the Michigan State University College of Human Medicine (MSU-CHM) has increased their class size to 850 students. The aim of this study was to determine if MSU-CHM alumni who graduate from an MSU-affiliated primary care residency from a single graduate medical education (GME) training program in Michigan are more likely to go on to practice in close proximity to the location of their training program immediately after graduation compared to non MSU-CHM alumni. Changes over time in the proportion of primary care graduates who received fellowship training immediately following residency were also compared between these groups. METHODS: A review of historical data was performed for all 2000-2016 primary care (Family Medicine, FM; Internal Medicine, IM; Internal Medicine-Pediatrics, IMP; Pediatrics, Peds) program graduates sponsored by Grand Rapids Medical Education Partners (GRMEP). Study variables included primary care program, gender, age at graduation, fellowship training, practice location immediately after graduation and undergraduate medical education location. Summary statistics were calculated for the data. Comparisons were made using the chi-square test or Fisher's Exact test when appropriate. Significance was assessed at p < 0.05. RESULTS: There were 478 primary care program graduates who went into practice immediately following graduation, 102 of whom also graduated from MSU-CHM. Just over half of the graduates were female and the average age at graduation was 32 years. There were 152 FM, 150 IM, 50 IMP and 126 Peds graduates. Those that graduated from both MSU-CHM and GRMEP were more likely to practice in Michigan immediately after residency training (79.4% vs 52.0%; p < 0.001), as well as within 100 miles of GRMEP (71.6% vs 46.4%; p < 0.001). There were 8% of MSU-CHM primary care graduates who went on to fellowship training from 2000 to 2009, increasing to 34% from 2010 to 2016 (p < 0.001). CONCLUSION: Medical school graduates of MSU-CHM who receive GME training in primary care are more likely to practice medicine within close proximity to their training site than non MSU-CHM graduates. However, plans for fellowship after training may add one caveat to this finding. PMID- 29793473 TI - Exploring the potential of a multi-level approach to improve capability for continuous organizational improvement and learning in a Swedish healthcare region. AB - BACKGROUND: Eldercare and care of people with functional impairments is organized by the municipalities in Sweden. Improving care in these areas is complex, with multiple stakeholders and organizations. Appropriate strategies to develop capability for continuing organizational improvement and learning (COIL) are needed. The purpose of our study was to develop and pilot-test a flexible, multilevel approach for COIL capability building and to identify what it takes to achieve changes in key actors' approaches to COIL. The approach, named "Sustainable Improvement and Development through Strategic and Systematic Approaches" (SIDSSA), was applied through an action-research and action-learning intervention. METHODS: The SIDSSA approach was tested in a regional research and development (R&D) unit, and in two municipalities handling care of the elderly and people with functional impairments. Our approach included a multilevel strategy, development loops of five flexible phases, and an action-learning loop. The approach was designed to support systems understanding, strategic focus, methodological practices, and change process knowledge - all of which required double-loop learning. Multiple qualitative methods, i.e., repeated interviews, process diaries, and documents, provided data for conventional content analyses. RESULTS: The new approach was successfully tested on all cases and adopted and sustained by the R&D unit. Participants reported new insights and skills. The development loop facilitated a sense of coherence and control during uncertainty, improved planning and problem analysis, enhanced mapping of context and conditions, and supported problem-solving at both the individual and unit levels. The systems-level view and structured approach helped participants to explain, motivate, and implement change initiatives, especially after working more systematically with mapping, analyses, and goal setting. CONCLUSIONS: An easily understood and generalizable model internalized by key organizational actors is an important step before more complex development models can be implemented. SIDSSA facilitated individual and group learning through action-learning and supported systems-level views and structured approaches across multiple organizational levels. Active involvement of diverse organizational functions and levels in the learning process was facilitated. However, the time frame was too short to fully test all aspects of the approach, specifically in reaching beyond the involved managers to front-line staff and patients. PMID- 29793475 TI - Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats. AB - BACKGROUND: This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. METHODS: Female SD rats (n = 136) were causally classified into two groups: the normal-drinking water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. RESULTS: The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). CONCLUSIONS: Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression. PMID- 29793476 TI - Place of death in patients with dementia and the association with comorbidities: a retrospective population-based observational study in Germany. AB - BACKGROUND: Due to increasing life expectancy, more and more older people are suffering from dementia and comorbidities. To date, little information is available on place of death for dementia patients in Germany. In addition, the association of place of death and comorbidities is unknown. METHODS: A population based cross-sectional survey was conducted in Westphalia-Lippe (Germany), based on the analysis of death certificates from 2011. Individuals with dementia >= 65 years were identified using the documented cause of death. In this context, all mentioned causes of death were included. In addition, ten selected comorbidities were also analyzed. The results were presented descriptively. Using multivariate logistic regression, place of death was analyzed for any association with comorbidities. RESULTS: A total of 10,364 death certificates were analyzed. Dementia was recorded in 1646 cases (15.9%; mean age 86.3 +/- 6.9 years; 67.3% women). On average, 1.5 +/- 1.0 selected comorbidities were present. Places of death were distributed as follows: home (19.9%), hospital (28.7%), palliative care unit (0.4%), nursing home (49.5%), hospice (0.9%), no details (0.7%). The death certificates documented cardiac failure in 43.6% of cases, pneumonia in 25.2%, and malignant tumour in 13.4%. An increased likelihood of dying in hospital compared to home or nursing home, respectively, was found for the following comorbidities (OR [95%-CI]): pneumonia (2.96 [2.01-4.35], p = 0.001); (2.38 [1.75-3.25], p = 0.001); renal failure (1.93 [1.26-2.97], p = 0.003); (1.65 [1.18-2.32], p = 0.003); and sepsis (13.73 [4.88-38.63], p = 0.001); (7.34 [4.21 12.78], p = 0.001). CONCLUSION: The most common place of death in patients with dementia is the retirement or nursing home, followed by hospital and home. Specific comorbidities, such as pneumonia or sepsis, correlated with an increased probability of dying in hospital. PMID- 29793478 TI - The long-term economic impacts of arthritis through lost productive life years: results from an Australian microsimulation model. AB - BACKGROUND: While the direct (medical) costs of arthritis are regularly reported in cost of illness studies, the 'true' cost to indivdiuals and goverment requires the calculation of the indirect costs as well including lost productivity due to ill-health. METHODS: Respondents aged 45-64 in the ABS Survey of Disability, Ageing and Carers 2003, 2009 formed the base population. We projected the indirect costs of arthritis using Health&WealthMOD2030 - Australia's first microsimulation model on the long-term impacts of ill-health in older workers - which incorporated outputs from established microsimulation models (STINMOD and APPSIM), population and labour force projections from Treasury, and chronic conditions trends for Australia. All costs of arthritis were expressed in real 2013 Australian dollars, adjusted for inflation over time. RESULTS: We estimated there are 54,000 people aged 45-64 with lost PLYs due to arthritis in 2015, increasing to 61,000 in 2030 (13% increase). In 2015, people with lost PLYs are estimated to receive AU$706.12 less in total income and AU$311.67 more in welfare payments per week than full-time workers without arthritis, and pay no income tax on average. National costs include an estimated loss of AU$1.5 billion in annual income in 2015, increasing to AU$2.4 billion in 2030 (59% increase). Lost annual taxation revenue was projected to increase from AU$0.4 billion in 2015 to $0.5 billion in 2030 (56% increase). We projected a loss in GDP of AU$6.2 billion in 2015, increasing to AU$8.2 billion in 2030. CONCLUSIONS: Significant costs of arthritis through lost PLYs are incurred by individuals and government. The effectiveness of arthritis interventions should be judged not only on healthcare use but quality of life and economic wellbeing. PMID- 29793477 TI - Feasibility of hospital-initiated non-facilitator assisted advance care planning documentation for patients with palliative care needs. AB - BACKGROUND: Advance Care Planning (ACP) and its documentation, accessible to healthcare professionals regardless of where patients are staying, can improve palliative care. ACP is usually performed by trained facilitators. However, ACP conversations would be more tailored to a patient's specific situation if held by a patient's clinical healthcare team. This study assesses the feasibility of ACP by a patient's clinical healthcare team, and analyses the documented information including current and future problems within the palliative care domains. METHODS: This multicentre study was conducted at the three Groningen Palliative Care Network hospitals in the Netherlands. Patients discharged from hospital with a terminal care indication received an ACP document from clinical staff (non palliative care trained staff at hospitals I and II; specialist palliative care nurses at hospital III) after they had held ACP conversations. An anonymised copy of this ACP document was analysed. Documentation rates of patient and contact details were investigated, and documentation of current and future problems were analysed both quantitatively and qualitatively. RESULTS: One hundred sixty ACP documents were received between April 2013 and December 2014, with numbers increasing for each consecutive 3-month time period. Advance directives were frequently documented (82%). Documentation rates of current problems in the social (24%), psychological (27%) and spiritual (16%) domains were low compared to physical problems (85%) at hospital I and II, but consistently high (> 85%) at hospital III. Of 545 documented anticipated problems, 92% were physical or care related in nature, 2% social, 5% psychological, and < 1% spiritual. Half of the anticipated non-physical problems originated from hospital III. CONCLUSIONS: Hospital-initiated ACP documentation by a patient's clinical healthcare team is feasible: the number of documents received per time period increased throughout the study period, and overall, documentation rates were high. Nonetheless, symptom documentation predominantly regards physical symptoms. With the involvement of specialist palliative care nurses, psychological and spiritual problems are addressed more frequently. Whether palliative care education for non palliative care experts will improve identification and documentation of non physical problems remains to be investigated. PMID- 29793479 TI - Prevalence and associated factors for stunting among 6-12 years old school age children from rural community of Humbo district, Southern Ethiopia. AB - BACKGROUND: Stunting is one of the most serious and challenging public health problems in Ethiopia, which constitute a significant obstacle to achieving better child health outcomes. This study aimed to assess the prevalence and factors associated with stunting among 6-12 years old children in Humbo district, Southern Ethiopia. METHODS: This was a cross-sectional study conducted among 633 children 6-12 years old living in Humbo district, Southern Ethiopia, from March to April, 2015. A multistage cluster sampling technique was used to select participants from households in eight Villages in the study area. Height was measured using standard methods and height for age Z-score was computed to assess stunting. EPI info version 3.5.4 was used for data entry, whereas Anthroplus software and SPSS version 20.0 were used for computation of height for age Z scores and statistical analyses respectively. Simple and multiple logistic regression analyses were used to examine factors associated with stunting in the study sample, using 95% confidence limits (statistical significance set at p < 0.050). RESULTS: Prevalence of stunting was 57%, about, 3.5% were severely stunted, 27.3% moderately stunted and 26.4% mildly stunted, and the mean (SD) was - 1.1 (+/-1.2). About 7 (1.1%) boys and 15 (2.4%) girls were severely stunted. Age groups 10-12 years had significantly higher rate of stunting than others. Age (AOR = 1.7, 95% CI = 1.1-2.6), big family size (AOR = 4.6, 95% CI = 2.2-9.5) and field disposal of wastes (AOR = 2.7, 95% CI = 1.2-5.8) were factors significantly associated with stunting. CONCLUSION: This study exposed high rate of stunting among school age children. Stunting remains a noticeable attribute of rural school age children. Findings suggest the need to implement evidence-based school aged rural children nutrition policy and strategies as well as need for intervention to improve domestic waste management system in the rural community. PMID- 29793481 TI - Insulin promotes progression of colon cancer by upregulation of ACAT1. AB - BACKGROUND: Insulin resistant and the progression of cancer is closely related. The aim of this study was to investigate the effect of insulin on the proliferation and migration of colon cancer cells and its underlying mechanism. METHODS: Colon carcinoma tissues from the 80 cases of colon cancer patients were collected. Immunohistochemistry was used to detect the expression of acyl coenzyme A: cholesterol acyltransferase1 (ACAT1), and we analyzed the correlation between hyperglycemia and ACAT1, hyperglycemia and metastasis. CCK8 assay and transwell assay were used to investigate the effect of different concentrations of insulin and ACAT1siRNA on human colon cancer cell line HT-29. ACAT1 mRNA expression and protein level in HT-29 cells were determined by real-time quantitative PCR and western blotting, respectively. RESULTS: Biopsies from patients with colon carcinoma showed hyperglycemia links ACAT1, lymph nodes metastasis and distant metastasis. Insulin markedly promoted cell proliferation and migration in human colon cancer HT-29 cells. Moreover, ACAT1mRNA expression and protein level were increased by insulin. ACAT1siRNA resulted in a complete inhibition of the ACAT1 mRNA expression. Consequently insulin-triggered cell proliferation and migration on colon cancer cells were inhibited. CONCLUSION: The progression of colon cancer has a positive correlation with hyperinsulinemia. Insulin-triggered cell proliferation and metastatic effects on colorectal cancer cells are mediated by ACAT1. Therefore, insulin could promote colon cancer progression by upregulation of ACAT1, which maybe is a potential therapeutic target for colon cancer. PMID- 29793482 TI - Association between timing and number of antenatal care visits on uptake of intermittent preventive treatment for malaria during pregnancy among Malawian women. AB - BACKGROUND: Malaria in pregnancy is a critical public health challenge, and intermittent preventive treatment for malaria during pregnancy (IPTp) has proven to be an effective intervention. However, access to and use of malaria interventions, including IPTp, remains a considerable problem among African women. This cross-sectional study investigated factors, including antenatal care (ANC) attendance (both numbers of visits and timing of the first visit) and socio demographics, associated with the uptake of the recommended IPTp dose among Malawian women. METHODS: A nationally representative sample of women with a live birth in the 2 years preceding the survey from the Malawi Demographic Health Survey 2015-2016 dataset was analysed. Self-reported data on socio-demographics, ANC attendance and IPTp uptake were collected using a questionnaire and analysed using logistic models. RESULTS: Of the 6549 included women, 1981 (30.2%) took the recommended three or more IPTp doses. Despite inadequate ANC visits, early ANC initiation increased the likelihood of these women taking the recommended IPTp dose; women who initiated ANC in the first [adjusted odds ratio (aOR) = 2.24; 95% confidence interval (CI) = 1.44-3.49] and second (aOR = 2.19; 95% CI = 1.56-3.08) trimesters were more likely to take the recommended IPTp dose compared to late initiators. The effect of the number of ANC visits on IPTp uptake was significant in married women (aOR = 1.68, 95% CI = 1.42-1.98), and the timing of first ANC visit was associated with IPTp uptake only among rural women (aOR = 2.13, 95% CI = 1.54-2.95). CONCLUSION: ANC attendance is vital in IPTp uptake. The results highlight the need for health care providers to encourage women, particularly those in high-risk groups, to make frequent ANC visits and receive early ANC initiation to ensure high coverage of the recommended IPTp dose. PMID- 29793480 TI - Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano sensing. AB - BACKGROUND: Acid-sensing ion channels (ASICs) are a group of amiloride-sensitive ligand-gated ion channels belonging to the family of degenerin/epithelial sodium channels. ASICs are predominantly expressed in both the peripheral and central nervous system and have been characterized as potent proton sensors to detect extracellular acidification in the periphery and brain. MAIN BODY: Here we review the recent studies focusing on the physiological roles of ASICs in the nervous system. As the major acid-sensing membrane proteins in the nervous system, ASICs detect tissue acidosis occurring at tissue injury, inflammation, ischemia, stroke, and tumors as well as fatiguing muscle to activate pain-sensing nerves in the periphery and transmit pain signals to the brain. Arachidonic acid and lysophosphocholine have been identified as endogenous non-proton ligands activating ASICs in a neutral pH environment. On the other hand, ASICs are found involved in the tether model mechanotransduction, in which the extracellular matrix and cytoplasmic cytoskeletons act like a gating-spring to tether the mechanically activated ion channels and thus transmit the stimulus force to the channels. Accordingly, accumulating evidence has shown ASICs play important roles in mechanotransduction of proprioceptors, mechanoreceptors and nociceptors to monitor the homoeostatic status of muscle contraction, blood volume, and blood pressure as well as pain stimuli. CONCLUSION: Together, ASICs are dual-function proteins for both chemosensation and mechanosensation involved in monitoring physiological homoeostasis and pathological signals. PMID- 29793483 TI - Chromosomal microarray analysis in developmental delay and intellectual disability with comorbid conditions. AB - BACKGROUND: Developmental delay (DD) and intellectual disability (ID) are frequently associated with a broad spectrum of additional phenotypes. Chromosomal microarray analysis (CMA) has been recommended as a first-tier test for DD/ID in general, whereas the diagnostic yield differs significantly among DD/ID patients with different comorbid conditions. METHODS: To investigate the genotype phenotype correlation, we examined the characteristics of identified pathogenic copy number variations (pCNVs) and compared the diagnostic yields among patient subgroups with different co-occurring conditions. RESULTS: This study is a retrospective review of CMA results generated from a mixed cohort of 710 Chinese patients with DD/ID. A total of 247 pCNVs were identified in 201 patients (28%). A large portion of these pCNVs were copy number losses, and the size of copy number losses was generally smaller than gains. The diagnostic yields were significantly higher in subgroups with co-occurring congenital heart defects (55%), facial dysmorphism (39%), microcephaly (34%) or hypotonia (35%), whereas co-occurring conditions of skeletal malformation (26%), brain malformation (24%) or epilepsy (24%) did not alter the yield. In addition, the diagnostic yield nominally correlated with ID severity. CONCLUSION: Varied yields exist in DD/ID patients with different phenotypic presentation. The presence of comorbid conditions can be among factors to consider when planning CMA. PMID- 29793485 TI - Healthcare students' perceptions about their role, confidence and competence to deliver brief public health interventions and advice. AB - BACKGROUND: Public health improvement has long been an important focus for the United Kingdom Department of Health. The Allied Health Professions (AHP) Federation has 84,000 members, such a large number of AHP professionals should play a role in public health initiatives, but it is not clear if they or the AHP students who will be the future healthcare workforce feel themselves equipped to do so. Our aim was to understand the perceptions of AHP students about their role in delivering public health advice. METHODS: AHP students were recruited in one teaching university from different departments. Participants were final year AHP students who had completed all clinical placements related to their course. All students were emailed an invitation to participate, and those interested were asked to contact the researchers to participate in one of several focus groups. Data were recorded, transcribed, and analysed using framework analysis by two independent researchers. RESULTS: Nineteen students were recruited and participated in four focus groups. The main themes produced by the data analysis were: understanding of public health issues, perceptions of their role in this, challenges and opportunities to develop a public health role, and preparation for a public health role. CONCLUSIONS: AHP students felt that they had a role in public health advice-giving, but barriers to providing this advice included their own lack of confidence and knowledge, time, and the environment of the clinical placement. They considered that there should be more teaching on public health issues, and that these should feature in both the curriculum and on clinical placement. PMID- 29793484 TI - Vascular inflammation and aortic stiffness: potential mechanisms of increased vascular risk in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition in which an important extra-pulmonary manifestation is cardiovascular disease. We hypothesized that COPD patients would have increased aortic inflammation and stiffness, as candidate mechanisms mediating increased cardiovascular risk, compared to two negative control groups: healthy never smokers and smokers without COPD. We also studied patients with COPD due to alpha 1 antitrypsin deficiency (alpha1ATD) as a comparator lung disease group. METHODS: Participants underwent 18F-Fluorodeoxyglucose (FDG) positron emission tomography imaging to quantify aortic inflammation as the tissue-to-blood-ratio (TBR) of FDG uptake. Aortic stiffness was measured by carotid-femoral aortic pulse wave velocity (aPWV). RESULTS: Eighty-five usual COPD (COPD due to smoking), 12 alpha1ATD-COPD patients and 12 each smokers and never-smokers were studied. There was no difference in pack years smoked between COPD patients and smokers (45 +/- 25 vs 37 +/- 19, p = 0.36), but alpha1ATD patients smoked significantly less (19 +/- 11, p < 0.001 for both). By design, spirometry measures were lower in COPD and alpha1ATD-COPD patients compared to smokers and never-smokers. Aortic inflammation and stiffness were increased in COPD (TBR: 1.90 +/- 0.38, aPWV: 9.9 +/- 2.6 m/s) and alpha1ATD patients (TBR: 1.94 +/- 0.43, aPWV: 9.5 +/- 1.8 m/s) compared with smokers (TBR: 1.74 +/- 0.30, aPWV: 7.8 +/- 1.8 m/s, p < 0.05 all) and never-smokers (TBR: 1.71 +/- 0.34, aPWV: 7.9 +/- 1.7 m/s, p <= 0.05 all). CONCLUSIONS: In this cross-sectional prospective study, novel findings were that both usual COPD and alpha1ATD-COPD patients have increased aortic inflammation and stiffness compared to smoking and never-smoking controls, regardless of smoking history. These findings suggest that the presence of COPD lung disease per se may be associated with adverse aortic wall changes, and aortic inflammation and stiffening are potential mechanisms mediating increased vascular risk observed in COPD patients. PMID- 29793486 TI - The influence of experimental inflammation and axotomy on leucine enkephalin (leuENK) distribution in intramural nervous structures of the porcine descending colon. AB - BACKGROUND: The enteric nervous system (ENS), located in the intestinal wall and characterized by considerable independence from the central nervous system, consists of millions of cells. Enteric neurons control the majority of functions of the gastrointestinal tract using a wide range of substances, which are neuromediators and/or neuromodulators. One of them is leucine-enkephalin (leuENK), which belongs to the endogenous opioid family. It is known that opioids in the gastrointestinal tract have various functions, including visceral pain conduction, intestinal motility and secretion and immune processes, but many aspects of distribution and function of leuENK in the ENS, especially during pathological states, remain unknown. RESULTS: During this experiment, the distribution of leuENK - like immunoreactive (leuENK-LI) nervous structures using the immunofluorescence technique were studied in the porcine colon in physiological conditions, during chemically-induced inflammation and after axotomy. The study included the circular muscle layer, myenteric (MP), outer submucous (OSP) and inner submucous plexus (ISP) and the mucosal layer. In control animals, the number of leuENK-LI neurons amounted to 4.86 +/- 0.17%, 2.86 +/- 0.28% and 1.07 +/- 0.08% in the MP, OSP and ISP, respectively. Generally, both pathological stimuli caused an increase in the number of detected leuENK-LI cells, but the intensity of the observed changes depended on the factor studied and part of the ENS. The percentage of leuENK-LI perikarya amounted to 11.48 +/- 0.96%, 8.71 +/- 0.13% and 9.40 +/- 0.76% during colitis, and 6.90 +/- 0.52% 8.46 +/- 12% and 4.48 +/- 0.44% after axotomy in MP, OSP and ISP, respectively. Both processes also resulted in an increase in the number of leuENK-LI nerves in the circular muscle layer, whereas changes were less visible in the mucosa during inflammation and axotomy did not change the number of leuENK-LI mucosal fibers. CONCLUSIONS: LeuENK in the ENS takes part in intestinal regulatory processes not only in physiological conditions, but also under pathological factors. The observed changes are probably connected with the participation of leuENK in sensory and motor innervation and the neuroprotective effects of this substance. Differences in the number of leuENK-LI neurons during inflammation and after axotomy may suggest that the exact functions of leuENK probably depend on the type of pathological factor acting on the intestine. PMID- 29793487 TI - The change of health-related quality of life after minimally invasive esophagectomy for esophageal cancer: a meta-analysis. AB - BACKGROUND: Short- and long-term health-related quality of life (HRQL) was severely affected after surgery. This study aimed to assess the direction and duration of HRQL from 3- to 24-month follow-ups after minimally invasive esophagectomy (MIE) for esophageal cancer. METHODS: A systematic literature search in MEDLINE, EMBASE, and the Cochrane database was performed for all potentially relevant studies published until February 2017. Studies were included if they addressed the question of HRQL with OERTC-QLQ-C30 and OES18. Primary outcomes were HRQL change at 3-month follow-up. Secondary outcomes were HRQL change from 3-, 6- (short-term) to 12- (mid-term), and/or 24-month (long-term) follow-ups. RESULTS: Six articles were included to estimate the change in 24 HRQL outcomes after MIE. Most of the patients' HRQL outcomes deteriorated at short term follow-up and some lasted to mid- or long-term after MIE. Patients' physical function and global QOL deteriorated from short- to long-term follow-ups, and emotional function had no change. The directions of dyspnea, pain, fatigue, insomnia, constipation, diarrhea, cough, and speech problems were increased. The deterioration in global function lasted 6 months, the increase in constipation and speech problems lasted 12 months, and insomnia increased more than 12 months after MIE. CONCLUSIONS: The emotional function had no change after MIE. The global QOL become worse during early postoperative period; the symptoms of constipation, speech problems, and insomnia increased for a long time after MIE. PMID- 29793489 TI - What do young people with rheumatic conditions in the UK think about research involvement? A qualitative study. AB - BACKGROUND: Involving people of all ages in health research is now widely advocated. To date, no studies have explored whether and how young people with chronic rheumatic conditions want to be involved in influencing health research. This study aimed to explore amongst young people with rheumatic conditions, 1) their experiences of research participation and involvement 2) their beliefs about research involvement and 3) beliefs about how young people's involvement should be organized in the future. METHODS: Focus groups discussions with young people aged 11-24 years with rheumatic conditions across the UK. Data was analysed using a qualitative Framework approach. RESULTS: Thirteen focus groups were held involving 63 participants (45 F: 18 M, mean age 16, range 10 to 24 years) across the UK. All believed that young people had a right to be involved in influencing research and to be consulted by researchers. However, experience of research involvement varied greatly. For many, the current project was the first time they had been involved. Amongst those with experience of research involvement, awareness of what they had been involved in and why was often low. Those who had previously participated in research appeared more positive and confident about influencing research in the future. However, all felt that there were limited opportunities for them to be both research participants and to get involved in research as public contributors. CONCLUSIONS: These findings suggest that there is an on-going need to both increase awareness of research involvement and participation of young people in rheumatology as well as amongst young people themselves. PMID- 29793488 TI - LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to moderate hypercholesterolemia. AB - BACKGROUND: Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). METHODS: This was a single center, controlled, randomized, open label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. RESULTS: LDL-C decreased by 23.3% during treatment with N (p < 0.0001) and by 25.6% during treatment with A (p < 0.0001); the LDL-C mean reduction was 36.4 (95% CI: 45,6-27,1) mg/dL during N treatment and 40.1 (95% CI: 49.2-30,9) mg/dL during A treatment. Tot-C decreased significantly (p < 0.0001) within each treatment period. HDL-C increase was negligible during A whereas it was significant during N. TG diminished markedly during A and not significantly during N. The difference between treatments was not statistically significant for all variables. No serious or severe adverse events occurred during the study. CONCLUSIONS: Our results confirm the clinically meaningful LDL-C lowering properties of monacolin K. At variance with a supplement already in the market (N), the novel association (A) of monacolin K with L-arginine, coenzime Q10 and ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03425630 . PMID- 29793490 TI - Geographic health inequalities in Norway: a Gini analysis of cross-county differences in mortality from 1980 to 2014. AB - BACKGROUND: This study aims at quantifying the level and changes over time of inequality in age-specific mortality and life expectancy between the 19 Norwegian counties from 1980 to 2014. METHODS: Data on population and mortality by county was obtained from Statistics Norway for 1980-2014. Life expectancy and age specific mortality rates (0-4, 5-49 and 50-69 age groups) were estimated by year and county. Geographic inequality was described by the absolute Gini index annually. RESULTS: Life expectancy in Norway has increased from 75.6 to 82.0 years, and the risk of death before the age of 70 has decreased from 26 to 14% from 1980 to 2014. The absolute Gini index decreased over the period 1980 to 2014 from 0.43 to 0.32 for life expectancy, from 0.012 to 0.0057 for the age group 50 69 years, from 0.0038 to 0.0022 for the age group 5-49 years, and from 0.0009 to 0.0006 for the age group 0-4 years. It will take between 2 and 32 years (national average 7 years) until the counties catch up with the life expectancy in the best performing county if their annual rates of increase remain unchanged. CONCLUSION: Using the absolute Gini index as a metric for monitoring changes in geographic inequality over time may be a valuable tool for informing public health policies. The absolute inequality in mortality and life expectancy between Norwegian counties has decreased from 1980 to 2014. PMID- 29793491 TI - Longitudinal construct validity of the minimum data set health status index. AB - BACKGROUND: The Minimum Data Set Health Status Index (MDS-HSI) is a generic, preference-based health-related quality of life (HRQOL) measure derived by mapping items from the Resident Assessment Instrument - Minimum Data Set (RAI MDS) assessment onto the Health Utilities Index Mark 2 classification system. While the validity of the MDS-HSI has been examined in cross-sectional settings, the longitudinal validity has not been explored. The objective of this study was to investigate the longitudinal construct validity of the MDS-HSI in a home care population. METHODS: This study utilized a retrospective cohort of home care patients in the Hamilton-Niagara-Haldimand-Brant health region of Ontario, Canada with at least two RAI-MDS Home Care assessments between January 2010 and December 2014. Convergent validity was assessed by calculating Spearman rank correlations between the change in MDS-HSI and changes in six validated indices of health domains that can be calculated from the RAI-MDS assessment. Known-groups validity was investigated by fitting multivariable linear regression models to estimate the mean change in MDS-HSI associated with clinically important changes in the six health domain indices and 15 disease symptoms from the RAI-MDS Home Care assessment, controlling for age and sex. RESULTS: The cohort contained 25,182 patients with two RAI-MDS Home Care assessments. Spearman correlations between the MDS-HSI change and changes in the health domain indices were all statistically significant and in the hypothesized small to moderate range [0.1 < rho < 0.5]. Clinically important changes in all of the health domain indices and 13 of the 15 disease symptoms were significantly associated with clinically important changes in the MDS-HSI. CONCLUSIONS: The findings of this study support the longitudinal construct validity of the MDS-HSI in home care populations. In addition to evaluating changes in HRQOL among home care patients in clinical research, economic evaluation, and health technology assessment, the MDS-HSI may be used in system-level applications using routinely collected population-level data. PMID- 29793492 TI - Beverage consumption patterns among 4-19 y old children in 2009-14 NHANES show that the milk and 100% juice pattern is associated with better diets. AB - BACKGROUND: Patterns of beverage consumption among children and adolescents can be indicative of food choices and total diet quality. METHODS: Analyses of beverage consumption patterns among 8119 children aged 4-19 y were based on the first 24-h recall of the National Health and Nutrition Examination Survey (2009 14 NHANES). Four pre-defined beverage patterns were: 1) milk pattern; 2) 100% juice pattern; 3) milk and 100% juice pattern; and 4) other caloric beverages. Food- and nutrient-based diet quality measures included the Healthy Eating Index 2010. RESULTS: Most children drank other caloric beverages, as opposed to milk (17.8%), 100% juice (5.6%), or milk and 100% juice (13.5%). Drinkers of milk and 100% juice had diets that did not differ from each other in total calories, total and added sugars, fiber, or vitamin E. Milk drinkers consumed more dairy and had higher intakes of calcium, potassium, vitamin A and vitamin D as compared to all other patterns. Juice drinkers consumed more total fruit, same amounts of whole fruit, and had higher intakes of vitamin C as compared to the other consumption patterns. Drinkers of both milk and 100% juice had the highest HEI 2010 scores of all the consumption patterns. CONCLUSIONS: Beverage consumption patterns built around milk and/or 100% juice were relatively uncommon. Promoting the drinking of milk and 100% juice, in preference to other caloric beverages, may be an effective strategy to improve children's diet quality. Restricting milk and 100% juice consumption may encourage the selection of other caloric beverages. PMID- 29793493 TI - Hypothesis and data-driven dietary patterns and colorectal Cancer survival: findings from Newfoundland and Labrador colorectal Cancer cohort. AB - BACKGROUND: Dietary patterns are commonly used in epidemiological research, yet there have been few studies assessing if and how research results may vary across dietary patterns. This study aimed to estimate the risk of mortality/recurrence/metastasis using different dietary patterns and comparison amongst the patterns. METHODS: Dietary patterns were identified by Cluster Analysis (CA), Principal Component Analysis (PCA), Alternate Mediterranean Diet score (altMED), Recommended Food Score (RFS) and Dietary Inflammatory Index (DII) scores using a 169-item food frequency questionnaire. Five hundred thirty-two colorectal cancer patients diagnosed between 1999 and 2003 in Newfoundland were followed-up until 2010. Overall Mortality (OM) and combined Mortality, Recurrence or Metastasis (cMRM) were identified. Comparisons were made with adjusted Cox proportional Hazards Ratios (HRs), correlation coefficients and the distributions of individuals in defined clusters by quartiles of factor and index scores. RESULTS: One hundred and seventy cases died from all causes and 29 had a cancer recurrence/metastasis during follow-up. Processed meats as classified by PCA (HR 1.82; 95% confidence interval (CI) 1.07-3.09), clusters characterized by meat and dairy products (HR 2.19; 95% CI 1.03-4.67) and total grains, sugar, soft drinks (HR 1.95; 95% CI 1.13-3.37) were associated with a higher risk of cMRM. Poor adherence to AltMED increased the risk of all-cause OM (HR 1.62; 95% CI 1.04 2.56). Prudent vegetable, high sugar pattern, RFS and DII had no significant association with both OM and cMRM. CONCLUSION: Estimation of OM and cMRM varied across dietary patterns which is attributed to the differences in the foundation of each pattern. PMID- 29793494 TI - Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK. AB - BACKGROUND: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. RESULTS: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners' preference, cost, concurrent disease, drug availability and previous history. CONCLUSIONS: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted. PMID- 29793496 TI - The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Several studies have evaluated the effect of inositol supplementation on lipid profiles among population with metabolic diseases; however, the findings are controversial. This review of randomized controlled trials (RCTs) was performed to summarize the evidence of the effects of inositol supplementation on lipid profiles among population with metabolic diseases. METHODS: Relevant RCTs studies were searched in Cochrane Library, EMBASE, MEDLINE, and Web of Science until October 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies, independently. To check for the heterogeneity among included studies Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary of the effect size. RESULTS: Overall, 14 RCTs were included into meta-analysis. Pooled results showed that inositol supplementation among patients with metabolic diseases significantly decreased triglycerides (SMD - 1.24; 95% CI, - 1.84, - 0.64; P < 0.001), total- (SMD - 1.09; 95% CI, - 1.83, - 0.55; P < 0.001), and LDL-cholesterol levels (SMD - 1.31; 95% CI, - 2.23, - 0.39; P = 0.005). There was no effect of inositol supplementation on HDL-cholesterol levels (SMD 0.20; 95% CI, - 0.27, 0.67; P = 0.40). CONCLUSIONS: Inositol supplementation may result in reduction in triglycerides, total- and LDL-cholesterol levels, but did not affect HDL cholesterol levels among patients with metabolic diseases. Additional prospective studies regarding the effect of inositol supplementation on lipid profiles in patients with metabolic diseases are necessary. PMID- 29793497 TI - Obituary: Remembering Professor David Cooper. PMID- 29793498 TI - Augmented reality-based electrode guidance system for reliable electroencephalography. AB - BACKGROUND: In longitudinal electroencephalography (EEG) studies, repeatable electrode positioning is essential for reliable EEG assessment. Conventional methods use anatomical landmarks as fiducial locations for the electrode placement. Since the landmarks are manually identified, the EEG assessment is inevitably unreliable because of individual variations among the subjects and the examiners. To overcome this unreliability, an augmented reality (AR) visualization-based electrode guidance system was proposed. METHODS: The proposed electrode guidance system is based on AR visualization to replace the manual electrode positioning. After scanning and registration of the facial surface of a subject by an RGB-D camera, the AR of the initial electrode positions as reference positions is overlapped with the current electrode positions in real time. Thus, it can guide the position of the subsequently placed electrodes with high repeatability. RESULTS: The experimental results with the phantom show that the repeatability of the electrode positioning was improved compared to that of the conventional 10-20 positioning system. CONCLUSION: The proposed AR guidance system improves the electrode positioning performance with a cost-effective system, which uses only RGB-D camera. This system can be used as an alternative to the international 10-20 system. PMID- 29793499 TI - Inflammatory and cytotoxic effects of bifenthrin in primary microglia and organotypic hippocampal slice cultures. AB - BACKGROUND: Pyrethroids, such as bifenthrin (BF), are among the most widely used class of insecticides that pose serious risks to human and wildlife health. Pyrethroids are proposed to affect astrocytic functions and to cause neuron injury in the central nervous system (CNS). Microglia are key cells involved in innate immune responses in the CNS, and microglia activation has been linked to inflammation and neurotoxicity. However, little information is known about the effects of BF-induced toxicity in primary microglial cells as well as in organotypic hippocampal slice cultures (OHSCs). METHODS: Oxidative stress and inflammatory responses induced by BF were evaluated in primary microglial cells and OHSCs incubated with different concentrations of BF (1-20 MUM) for 4 and 24 h. mRNA and protein synthesis of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), nuclear erythroid-2 like factor-2 (Nrf 2), and microsomal prostaglandin synthase-1 (mPGES-1) was also studied by qPCR and Western blot. Cell viability was analyzed by MTT-tetrazolio (MTT) and lactate dehydrogenase (LDH) assays. Neurotoxicity in OHSCs was analyzed by propidium iodide (PI) staining and confocal microscopy. RESULTS: Exposure of microglial cells to BF for 24 h resulted in a dose-dependent reduction in the number of viable cells. At sub-cytotoxic concentrations, BF increased reactive oxygen species (ROS), TNF-alpha synthesis, and prostaglandin E2 (PGE2) production, at both 4- and 24-h time points, respectively. Furthermore, BF incubation decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and increased lipid peroxidation, protein oxidation, and H2O2 formation. In addition, BF significantly induced protein synthesis and mRNA expression of oxidative and inflammatory mediators after 4 and 24 h, including Nrf-2, COX-2, mPGES-1, and nuclear factor kappaB (NF-kappaB). A 24-h exposure of OHSCs to BF also increased neuronal death compared to untreated controls. Furthermore, depletion of microglia from OHSCs potently enhanced neuronal death induced by BF. CONCLUSIONS: Overall, BF exhibited cytotoxic effects in primary microglial cells, accompanied by the induction of various inflammatory and oxidative stress markers including the Nrf-2/COX-2/mPGES-1/NF-kappaB pathways. Moreover, the study provided evidence that BF induced neuronal death in OHSCs and suggests that microglia exert a protective function against BF toxicity. PMID- 29793500 TI - Perinatal Pb2+ exposure alters the expression of genes related to the neurodevelopmental GABA-shift in postnatal rats. AB - BACKGROUND: Lead (Pb2+) is an environmental neurotoxicant that disrupts neurodevelopment, communication, and organization through competition with Ca2+ signaling. How perinatal Pb2+ exposure affects Ca2+-related gene regulation remains unclear. However, Ca2+ activates the L-Type voltage sensitive calcium channel beta-3 subunit (Ca-beta3), which autoregulates neuronal excitability and plays a role in the GABA-shift from excitatory-to-inhibitory neurotransmission. METHOD: A total of eight females (n = 4 Control and n = 4 Perinatal) and four males (n = 2 Control and n = 2 Perinatal) rats were used as breeders to serve as Dams and Sires. The Dam's litters each ranged from N = 6-10 pups per litter (M = 8, SD = 2), irrespective of Pb2+ treatment, with a majority of males over females. Since there were more males in each of the litters than females, to best assess and equally control for Pb2+- and litter-effects across all developmental time-points under study, female pups were excluded due to an insufficient sample size availability from the litter's obtained. From the included pup litters, 24 experimentally naive male Long Evans hooded rat pups (Control N = 12; Pb2+ N = 12) were used in the present study. Brains were extracted from rat prefrontal cortex (PFC) and hippocampus (HP) at postnatal day (PND) 2, 7, 14 and 22, were homogenized in 1 mL of TRIzol reagent per 100 mg of tissue using a glass-Teflon homogenizer. Post-centrifugation, RNA was extracted with chloroform and precipitated with isopropyl alcohol. RNA samples were then re-suspended in 100 MUL of DEPC treated H2O. Next, 10 MUg of total RNA was treated with RNase-free DNase (Qiagen) at 37 degrees C for 1 h and re-purified by a 3:1 phenol/chloroform extraction followed by an ethanol precipitation. From the purified RNA, 1 MUg was used in the SYBR GreenER Two-Step qRT-PCR kit (Invitrogen) for first strand cDNA synthesis and the quantitative real-time PCR (qRT-PCR). The effects of perinatal Pb2+ exposure on genes related to early neuronal development and the GABA-shift were evaluated through the expression of: Ca-beta3, GABAAR-beta3, NKCC1, KCC2, and GAD 80, 86, 65, and 67 isoforms. RESULTS: Perinatal Pb2+ exposure significantly altered the GABA-shift neurodevelopmental GOI expression as a function of Pb2+ exposure and age across postnatal development. Dramatic changes were observed with Ca-beta3 expression consistent with a Pb2+ competition with L-type calcium channels. By PND 22, Ca beta3 mRNA was reduced by 1-fold and 1.5-fold in PFC and HP respectively, relative to controls. All HP GABA-beta3 mRNA levels were particularly vulnerable to Pb2+ at PND 2 and 7, and both PFC and HP were negatively impacted by Pb2+ at PND 22. Additionally, Pb2+ altered both the PFC and HP immature GAD 80/86 mRNA expression particularly at PND 2, whereas mature GAD 65/67 were most significantly affected by Pb2+ at PND 22. CONCLUSIONS: Perinatal Pb2+ exposure disrupts the expression of mRNAs related to the GABA-shift, potentially altering the establishment, organization, and excitability of neural circuits across development. These findings offer new insights into the altered effects Pb2+ has on the GABAergic system preceding what is known regarding Pb2+ insults unto the glutamatergic system. PMID- 29793495 TI - Casein kinase 1alpha: biological mechanisms and theranostic potential. AB - Casein kinase 1alpha (CK1alpha) is a multifunctional protein belonging to the CK1 protein family that is conserved in eukaryotes from yeast to humans. It regulates signaling pathways related to membrane trafficking, cell cycle progression, chromosome segregation, apoptosis, autophagy, cell metabolism, and differentiation in development, circadian rhythm, and the immune response as well as neurodegeneration and cancer. Given its involvement in diverse cellular, physiological, and pathological processes, CK1alpha is a promising therapeutic target. In this review, we summarize what is known of the biological functions of CK1alpha, and provide an overview of existing challenges and potential opportunities for advancing theranostics. PMID- 29793501 TI - Long-acting reversible contraceptive use in the post-abortion period among women seeking abortion in mainland China: intentions and barriers. AB - BACKGROUND: This study aimed to describe the intentions of and barriers to the use of long-acting reversible contraceptives (LARCs) in the post-abortion period among women seeking abortion in mainland China. METHODS: A cross-sectional study was conducted from July 2015 to December 2015 using a waiting room questionnaire. A total of 381 women seeking abortions were recruited at a public hospital abortion clinic. The outcome variable was an 'intention-to-use' LARCs in the immediate post-abortion period. Chi-square tests were used to assess associations between categorical variables. Statistically significant variables (p <= 0.05) were then further analyzed by logistic regression. RESULTS: Among 381 respondents, 42.5% intended to use LARCs in the immediate post-abortion period; 35.2% intended to use intra-uterine devices (IUDs); and 13.9% intended to use implants. Previous use of LARC was a predictor for an intention to use LARCs (odds ratio [OR] = 2.41; 95% confidence interval [CI]: 1.06-5.47). Participants with one or no child had reduced odds for an intention to use LARC (OR = 0.32, 95% CI: 0.15-0.47 and OR = 0.29, 95% CI: 0.13-0.68, respectively). Women with a higher sex frequency (at least once per week) showed increased odds for LARC use (OR = 3.34; 95% CI: 1.03-10.78) and married women were more likely to use LARC than single women (OR = 1.57; 95% CI:1.00-2.47). Women who planned to have another baby within two years were more likely not to use LARCs in the immediate post-abortion period (OR = 0.97; 95% CI: 0.43-2.12). Barriers to the use of LARCs were anxiety relating to impaired future fertility (56.2%), LARCs being harmful to health (45.2%), irregular bleeding (44.3%), risk of IUD failure (41.6%) and lack of awareness with respect to LARCs (36.1%). CONCLUSIONS: Intention to use LARCs was predicted by marital status, frequency of sexual activity, number of children, planned timing of next pregnancy, and previous LARC use. Impaired future fertility, being harmful to health, irregular bleeding, risk of complications, and lack of awareness with regards to LARCs were the main barriers in their potential use. PMID- 29793502 TI - Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. METHODS: Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion. RESULTS: DHEA treatment induced some aspects of PCOS in wild type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling. CONCLUSIONS: In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism. PMID- 29793503 TI - Abnormalities of hair structure and skin histology derived from CRISPR/Cas9-based knockout of phospholipase C-delta 1 in mice. AB - BACKGROUND: Hairless mice have been widely applied in skin-related researches, while hairless pigs will be an ideal model for skin-related study and other biomedical researches because of the similarity of skin structure with humans. The previous study revealed that hairlessness phenotype in nude mice is caused by insufficient expression of phospholipase C-delta 1 (PLCD1), an essential molecule downstream of Foxn1, which encouraged us to generate PLCD1-deficient pigs. In this study, we plan to firstly produce PLCD1 knockout (KO) mice by CRISPR/Cas9 technology, which will lay a solid foundation for the generation of hairless PLCD1 KO pigs. METHODS: Generation of PLCD1 sgRNAs and Cas 9 mRNA was performed as described (Shao in Nat Protoc 9:2493-2512, 2014). PLCD1-modified mice (F0) were generated via co-microinjection of PLCD1-sgRNA and Cas9 mRNA into the cytoplasm of C57BL/6J zygotes. Homozygous PLCD1-deficient mice (F1) were obtained by intercrossing of F0 mice with the similar mutation. RESULTS: PLCD1-modified mice (F0) showed progressive hair loss after birth and the genotype of CRISPR/Cas9-induced mutations in exon 2 of PLCD1 locus, suggesting the sgRNA is effective to cause mutations that lead to hair growth defect. Homozygous PLCD1 deficient mice (F1) displayed baldness in abdomen and hair sparse in dorsa. Histological abnormalities of the reduced number of hair follicles, irregularly arranged and curved hair follicles, epidermal hyperplasia and disturbed differentiation of epidermis were observed in the PLCD1-deficient mice. Moreover, the expression level of PLCD1 was significantly decreased, while the expression levels of other genes (i.e., Krt1, Krt5, Krt13, loricrin and involucrin) involved in the differentiation of hair follicle were remarkerably increased in skin tissues of PLCD1-deficient mice. CONCLUSIONS: In conclusion, we achieve PLCD1 KO mice by CRISPR/Cas9 technology, which provide a new animal model for hair development research, although homozygotes don't display completely hairless phenotype as expected. PMID- 29793505 TI - Status of imported malaria on Reunion Island in 2016. AB - BACKGROUND: Autochthonous malaria has been eliminated from Reunion in 1979. To prevent secondary transmission and re-emergence of autochthonous malaria, permanent epidemiologic and entomological surveillance and vector control measures are conducted around imported malaria cases. Results of local malaria surveillance (clinical data and results of epidemiological and entomological investigations around cases) were collected for 2013-2016 and were analysed according to historical data and to the exchanges with malaria-affected areas (estimated by airport data). RESULTS: Form 2013 to 2016, 95 imported malaria cases have been detected in Reunion Island: 42% of cases occurred in the area of repartition of Anopheles arabiensis, but Anopheles mosquitoes were present only around seven cases including one gametocyte carrier. No autochthonous or introduced case has occurred during this period. The lack of chemoprophylaxis or poor adherence was found in the majority (96%) of malaria cases between 2013 and 2016, regardless of trip type. Affinity tourism in Madagascar and Comoros was the cause of 65% of imported malaria cases. DISCUSSION: The incidence of imported malaria and the incidence rate per 100,000 travellers has continuously decreased since 2001. Now with the drastic decrease of malaria transmission in the Comoros archipelago, most of imported malaria cases in Reunion Island have been contaminated in Madagascar. Immigrants regularly resident in Reunion Island, which travel to malaria endemic countries (mainly Madagascar) to visit their friends and relatives (VFRs) represent a high-risk group of contracting malaria. VFRs, low adherence to pre-travel recommendations, in particular, the compliance on the use of chemoprophylaxis are the main drivers of imported malaria in Reunion Island. Furthermore as previously described, some general practitioners in Reunion Island are always not sufficiently aware of the official recommendations for prescriptions of prophylactic treatments. CONCLUSION: Social mobilization targeted on the Malagasy community in Reunion Island could help to decrease the burden of imported malaria in Reunion Island. Because of the low number of gametocyte carriers and the absence of an Anopheles mosquito population when most malaria cases were imported those last 4 years, the risk of the appearance of introduced malaria cases and indigenous malaria cases appears low in Reunion Island. PMID- 29793504 TI - Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses. AB - BACKGROUND: Severe hypoglycemia induces brain edema by upregulating aquaporin-4 (AQP4) expression and by degrading tight junctions. Acute severe hypoglycemia induces a proinflammatory environment that may contribute to a disruption in the epithelial barrier by decreasing tight junction protein expression. Interestingly, the altered AQP4 expression has been considered to play a critical role in neuroinflammation during acute brain injury. It has been shown that AQP4 deletion reduces brain inflammation in AQP4-null mice after intracerebral LPS injection. However, the effect of AQP4 deletion regarding protection against hypoglycemia-induced blood-brain barrier (BBB) breakdown is unknown. METHODS: An acute severe hypoglycemic stress model was established via injection of 4 unit/kg body weight of insulin. Evans blue (EB) staining and water measurement were used to assess BBB permeability. Western blot, reverse transcription polymerase chain reaction, and immunofluorescence were used to detect the expression of related proteins. The production of cytokines was assessed via enzyme-linked immunosorbent assay. RESULTS: Hypoglycemia-induced brain edema and BBB leakage were reduced in AQP4-/- mice. AQP4 deletion upregulated PPAR-gamma and inhibited proinflammatory responses. Moreover, knockdown of aquaporin-4 by small interfering RNA in astrocytes co-cultured with endothelial cells effectively reduced transendothelial permeability and degradation of tight junctions. Treatment with PPAR-gamma inhibitors showed that upregulation of PPAR-gamma was responsible for the protective effect of AQP4 deletion under hypoglycemic conditions. CONCLUSIONS: Our data suggest that AQP4 deletion protects BBB integrity by reducing inflammatory responses due to the upregulation of PPAR gamma expression and attenuation of proinflammatory cytokine release. Reduction in AQP4 may be protective in acute severe hypoglycemia. PMID- 29793506 TI - Nucleocapsid protein-dependent assembly of the RNA packaging signal of Middle East respiratory syndrome coronavirus. AB - BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) consists of a positive-sense, single-stranded RNA genome and four structural proteins: the spike, envelope, membrane, and nucleocapsid protein. The assembly of the viral genome into virus particles involves viral structural proteins and is believed to be mediated through recognition of specific sequences and RNA structures of the viral genome. METHODS AND RESULTS: A culture system for the production of MERS coronavirus-like particles (MERS VLPs) was determined and established by electron microscopy and the detection of coexpressed viral structural proteins. Using the VLP system, a 258-nucleotide RNA fragment, which spans nucleotides 19,712 to 19,969 of the MERS-CoV genome (designated PS258(19712-19969)ME), was identified to function as a packaging signal. Assembly of the RNA packaging signal into MERS VLPs is dependent on the viral nucleocapsid protein. In addition, a 45-nucleotide stable stem-loop substructure of the PS258(19712-19969)ME interacted with both the N-terminal domain and the C-terminal domain of the viral nucleocapsid protein. Furthermore, a functional SARS-CoV RNA packaging signal failed to assemble into the MERS VLPs, which indicated virus-specific assembly of the RNA genome. CONCLUSIONS: A MERS-oV RNA packaging signal was identified by the detection of GFP expression following an incubation of MERS VLPs carrying the heterologous mRNA GFP-PS258(19712-19969)ME with virus permissive Huh7 cells. The MERS VLP system could help us in understanding virus infection and morphogenesis. PMID- 29793507 TI - Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. AB - Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson's disease. Failure of cellular energy metabolism has long been implicated in sporadic Parkinson's disease and recent research on rare inherited forms of Parkinson's disease have added further weight to the importance of energy metabolism in the disease pathogenesis. There exists a new class of anti-diabetic insulin sensitizers in development that inhibit the mitochondrial pyruvate carrier (MPC), a protein which mediates the import of pyruvate across the inner membrane of mitochondria. Pharmacological inhibition of the MPC was recently found to be strongly neuroprotective in multiple neurotoxin-based and genetic models of neurodegeneration which are relevant to Parkinson's disease. In this review, we summarize the neuroprotective effects of MPC inhibition and discuss the potential putative underlying mechanisms. These mechanisms involve augmentation of autophagy via attenuation of the activity of the mammalian target of rapamycin (mTOR) in neurons, as well as the inhibition of neuroinflammation, which is at least partly mediated by direct inhibition of MPC in glia cells. We conclude that MPC is a novel and potentially powerful therapeutic target that warrants further study in attempts to slow Parkinson's disease progression. PMID- 29793508 TI - GSK-3beta inhibits autophagy and enhances radiosensitivity in non-small cell lung cancer. AB - BACKGROUND: Radiotherapy is one of the most common and effective treatment methods for cancer, and improving the radiosensitivity of tumor tissues during the treatment process is vital. We report the mechanisms of glycogen synthase kinase 3 (GSK-3) beta-regulated autophagy and the effects of autophagy on radiosensitivity in non-small cell lung cancer (NSCLC). METHOD: Immunohistochemical staining was performed to determine GSK-3beta tissue expression in 89 NSCLC patients with follow-up data and the expression status of GSK-3beta and autophagy in NSCLC tissues after X-ray radiotherapy. Western blots were used to quantitate changes in autophagy-related protein expression after A549 cells were treated with GSK-3beta inhibitors and after H460 cells were transfected with GSK-3beta mutants with different activities and X-ray irradiated. Clonogenic assays were used to measure the effect of autophagy on cellular proliferation. RESULTS: GSK-3beta expression positively correlated with NSCLC differentiation (P < 0.05), and GSK-3beta negativity was associated with a better prognosis in 89 NSCLC patients. After X-ray irradiation, the expression levels of GSK-3beta and p62 were decreased in NSCLC tissues, and the expression levels of the autophagy-related protein LC3 were increased. A549 and H460 cells were selected as representative GSK-3beta-high and GSK-3beta-low expression cell lines. After transfecting H460 cells with different GSK-3beta mutants [wild type GSK-3beta (GSK-3beta-WT), constitutively active GSK-3beta (GSK-3beta-S9A), and catalytically inactive GSK-3beta (GSK-3beta-K85R)] and subjecting these cells to X-ray irradiation, AMPK and LC3 expression levels decreased, and p62 expression levels increased. These effects were particularly significant for the GSK-3beta S9A mutant. In A549 cells, after GSK-3beta inhibition and X-ray irradiation, AMPK and LC3 protein expression levels increased. Moreover, when autophagy was inhibited, cell proliferation decreased. CONCLUSION: Our studies revealed that GSK-3beta expression is associated with NSCLC differentiation, and patients with GSK-3beta-negative tumors had a better prognosis. X-ray irradiation inhibited GSK 3beta expression and promoted autophagy. Therefore, GSK-3beta inhibits autophagy and enhances the radiosensitivity of NSCLC cells. PMID- 29793509 TI - Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer's disease. AB - BACKGROUND: Because of their low levels of expression and the inadequacy of current research tools, CB2 cannabinoid receptors (CB2R) have been difficult to study, particularly in the brain. This receptor is especially relevant in the context of neuroinflammation, so novel tools are needed to unveil its pathophysiological role(s). METHODS: We have generated a transgenic mouse model in which the expression of enhanced green fluorescent protein (EGFP) is under the control of the cnr2 gene promoter through the insertion of an Internal Ribosomal Entry Site followed by the EGFP coding region immediately 3' of the cnr2 gene and crossed these mice with mice expressing five familial Alzheimer's disease (AD) mutations (5xFAD). RESULTS: Expression of EGFP in control mice was below the level of detection in all regions of the central nervous system (CNS) that we examined. CB2R-dependent-EGFP expression was detected in the CNS of 3-month-old AD mice in areas of intense inflammation and amyloid deposition; expression was coincident with the appearance of plaques in the cortex, hippocampus, brain stem, and thalamus. The expression of EGFP increased as a function of plaque formation and subsequent microgliosis and was restricted to microglial cells located in close proximity to neuritic plaques. AD mice with CB2R deletion exhibited decreased neuritic plaques with no changes in IL1beta expression. CONCLUSIONS: Using a novel reporter mouse line, we found no evidence for CB2R expression in the healthy CNS but clear up-regulation in the context of amyloid-triggered neuroinflammation. Data from CB2R null mice indicate that they play a complex role in the response to plaque formation. PMID- 29793510 TI - Analyzing the impacts of global trade and investment on non-communicable diseases and risk factors: a critical review of methodological approaches used in quantitative analyses. AB - BACKGROUND: A key mechanism through which globalization has impacted health is the liberalization of trade and investment, yet relatively few studies to date have used quantitative methods to investigate the impacts of global trade and investment policies on non-communicable diseases and risk factors. Recent reviews of this literature have found heterogeneity in results and a range of quality across studies, which may be in part attributable to a lack of conceptual clarity and methodological inconsistencies. METHODS: This study is a critical review of methodological approaches used in the quantitative literature on global trade and investment and diet, tobacco, alcohol, and related health outcomes, with the objective of developing recommendations and providing resources to guide future robust, policy relevant research. A review of reviews, expert review, and reference tracing were employed to identify relevant studies, which were evaluated using a novel quality assessment tool designed for this research. RESULTS: Eight review articles and 34 quantitative studies were identified for inclusion. Important ways to improve this literature were identified and discussed: clearly defining exposures of interest and not conflating trade and investment; exploring mechanisms of broader relationships; increasing the use of individual-level data; ensuring consensus and consistency in key confounding variables; utilizing more sector-specific versus economy-wide trade and investment indicators; testing and adequately adjusting for autocorrelation and endogeneity when using longitudinal data; and presenting results from alternative statistical models and sensitivity analyses. To guide the development of future analyses, recommendations for international data sources for selected trade and investment indicators, as well as key gaps in the literature, are presented. CONCLUSION: More methodologically rigorous and consistent approaches in future quantitative studies on the impacts of global trade and investment policies on non-communicable diseases and risk factors can help to resolve inconsistencies of existing research and generate useful information to guide policy decisions. PMID- 29793511 TI - Development of a GFP expression vector for Cucurbit chlorotic yellows virus. AB - BACKGROUND: Cucurbit chlorotic yellows virus (CCYV), a bipartite crinivirus, causes chlorotic leaf spots and yellowing symptoms on cucurbit leaves. We previously developed an infectious clone of CCYV. Limited work has been conducted on the construction of a crinivirus green fluorescence protein (GFP) expression vector to date. FINDING: We constructed a CCYV GFP expression vector using the "add a gene" strategy based on CCYV RNA2 cDNA constrcut. Three resultant clones, pCCYVGFPSGC, pCCYVGFPCGC, and pCCYVGFPCGS, were constructed with different promoters used to initiate GFP and CP expression. At 25 dpi GFP fluorescence was detectable not only in leaf veins but also in the surrounding cells. pCCYVGFPCGC infected cucumber leaves exhibited cell spread at 25 dpi, whereas pCCYVGFPSGC and pCCYVGFPCGS were mainly found in single cells. Further observation of pCCYVGFPCGC GFP expression at 30 dpi, 40 dpi, and 50 dpi showed phloem-limited localization in the systemic leaves. CONCLUSIONS: We developed of a CCYV GFP expression vector that will be useful for further study of CCYV movement in cucurbits. PMID- 29793512 TI - Getting up close and personal with UK genomics and beyond. AB - Stephan Beck discusses recent developments in sharing personal genomes as part of the Personal Genome Project in the UK and globally, and how these efforts are advancing research. PMID- 29793514 TI - Correction to: Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway. AB - In the publication of this article [1], there was an error in Figs. 2, 3 and 6. PMID- 29793515 TI - Prolonged corticosteroid treatment in acute respiratory distress syndrome: impact on mortality and ventilator-free days. PMID- 29793513 TI - Molecular characterizations of Cryptosporidium spp. and Enterocytozoon bieneusi in brown rats (Rattus norvegicus) from Heilongjiang Province, China. AB - BACKGROUND: Cryptosporidium spp. and Enterocytozoon bieneusi are prevalent zoonotic pathogens responsible for the high burden of diarrheal diseases worldwide. Rodents are globally overpopulated and are known as reservoirs or carriers of a variety of zoonotic pathogens including Cryptosporidium spp. and E. bieneusi. However, few data are available on genetic characterizations of both pathogens in rodents in China. The aim of the present work was to determine the prevalence and genetic characterizations of Cryptosporidium spp. and E. bieneusi in brown rats (Rattus norvegicus) from Heilongjiang, China. METHODS: A total of 242 wild brown rats were captured in Heilongjiang Province of China. A fresh fecal specimen was collected directly from the intestinal and rectal content of each brown rat. All the fecal specimens were examined for the presence of Cryptosporidium spp. and E. bieneusi by PCR and sequencing of the partial small subunit (SSU) rRNA gene and the internal transcribed spacer (ITS) region of the rRNA gene of the two pathogens, respectively. RESULTS: The infection rate was 9.1% (22/242) for Cryptosporidium spp. and 7.9% (19/242) for E. bieneusi. Sequence analysis confirmed the presence of C. ubiquitum (1/22, 4.5%) and three genotypes of Cryptosporidium, including Cryptosporidium rat genotype I (14/22, 63.6%), Cryptosporidium rat genotype IV (6/22, 27.3%) and Cryptosporidium suis like genotype (1/22, 4.5%). Meanwhile, two E. bieneusi genotypes were identified, including D (17/19, 89.5%) and Peru6 (2/19, 10.5%). CONCLUSIONS: To the best of our knowledge, Enterocytozoon bieneusi genotype Peru6 was identified in rodents for the first time globally and Cryptosporidium rat genotype I and Cryptosporidium rat genotype IV were found in rats in China for the first time. The finding of zoonotic C. ubiquitum and C. suis-like genotype, as well as E. bieneusi genotypes, suggests that brown rats pose a threat to human health. It is necessary to control brown rat population in the investigated areas and improve local people's awareness of the transmission risk of the two pathogens from brown rats to humans. PMID- 29793516 TI - Immediate effects of rest periods on balance control in patients after stroke. A randomized controlled pilot trial. AB - OBJECTIVES: This randomized controlled trial evaluates the effects of two different rest periods between as set of balance exercises after stroke during inpatient rehabilitation. RESULTS: Twenty patients after stroke [11 males; mean (SD) age 65.4 (11.5) years; duration of illness 5.3 (3.4) weeks; 16 (80%) left sided strokes] were randomly allocated into two groups of either a full rest (FR) of 4 min (n = 10) or a short rest (SR) of 1 min between exercise sets (n = 10). Patients improved from baseline until immediately after exercises in one-leg standing time on the affected leg [SR: mean difference 5.1 s (SD 10.3) and FR: 2.0 s (2.4)] and tandem standing time (TST). [SR: 14.9 s (SD 24.6) and FR: 5.7 s (12.0)], but OLST and TST did not differ significantly between groups (p = 0.35 and p = 0.52, respectively). Trial registration The study was registered retrospectively in the German Register of Clinical Trials with the ID: DRKS00013979. PMID- 29793517 TI - Physioxia: a more effective approach for culturing human adipose-derived stem cells for cell transplantation. AB - BACKGROUND: Although typically cultured at an atmospheric oxygen concentration (20-21%), adipose-derived stem cells (ASCs) reside under considerable low oxygen tension (physioxia) in vivo. In the present study, we explored whether and how physioxia could be a more effective strategy for culturing ASCs for transplantation. METHODS: After isolation, human ASCs were cultured under physioxia (2% O2) and hyperoxia (20% O2) until assayed. WST-8, Transwell, tube formation, beta-galactosidase staining, and annexin V-FITC/PI assays were used to evaluate cell proliferation, migration, angiogenesis, senescence, and apoptosis, respectively. Survivability was determined by an ischemia model in vitro and nude mouse model in vivo, and the underlying metabolic alterations were investigated by fluorescence staining, flow cytometry, and real-time polymerase chain reaction. RESULTS: Compared with those in the hyperoxia group, cells in the physioxia group exhibited increased proliferation, migration, and angiogenesis, and decreased senescence and apoptosis. The increased survival rate of ASCs cultured in physioxia was found both in ischemia model in vitro and in vivo. The underlying metabolic reprogramming was also monitored and showed decreased mitochondrial mass, alkalized intracellular pH, and increased glucose uptake and glycogen synthesis. CONCLUSIONS: These results suggest that physioxia is a more effective environment in which to culture ASCs for transplantation owing to the maintenance of native bioactivities without injury by hyperoxia. PMID- 29793518 TI - A dose-response study of aerobic training for oxygen uptake, oxidative stress and cardiac autonomic function in type 2 diabetes mellitus: study protocol for a randomized controlled trial. AB - BACKGROUND: Cardiac autonomic neuropathy is a commonly overlooked complication of type 2 diabetes mellitus (T2DM) characterized by an imbalance between sympathetic and parasympathetic supply to the heart, which contributes to cardiovascular morbidity and mortality. T2DM has also been shown to negatively influence oxygen kinetics and increase oxidative stress, which may be linked to the development of various chronic complications. Aerobic training has been reported to improve oxygen uptake, antioxidant defense, and cardiac autonomic function in T2DM; however, the effects of varying doses of exercise on these variables are not known. Therefore, the aim of the present study is to explore the effects of manipulating training variables (volume and intensity) on the regulation of oxygen uptake response, oxidative stress, and cardiac autonomic function in patients with T2DM. METHODS: We will recruit 60 patients with T2DM, who will be randomly allocated into one of the three aerobic training groups: low-intensity, low-volume training; low-intensity, high volume-training; high-intensity, high volume training; or to the control group receiving no supervised exercise. All participants will be assessed for the rate of oxygen uptake, levels of antioxidant enzymes and cardiac autonomic function at baseline and after 12 weeks of training. Secondary outcome measures will include cardiometabolic risk factors and body composition. DISCUSSION: Despite a large body of evidence on the efficacy of aerobic training in the prevention and treatment of T2DM, there is no unequivocal exercise prescription for the same. Oxygen kinetics and oxidative stress are highly sensitive to the magnitude of physical activity. It would therefore, be interesting to study their interaction with chronic exposure to various doses of exercises and explore the optimal volume and intensity to bring about improvements in these parameters. TRIAL REGISTRATION: Clinical Trials Registry - India, CTRI2017/08/009459 . Registered on 23 August 2017. Retrospectively registered. PMID- 29793519 TI - High-grade B-cell lymphoma with MYC and BCL2 rearrangements arising in a composite lymphoma. AB - BACKGROUND: We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements within the same needle biopsy in which a clonal relationship between the FL and high-grade B cell lymphoma components was demonstrated by molecular cytogenetics. CASE PRESENTATION: An 85-year-old man presented with masses in his neck and right groin. Cutting needle biopsy of the inguinal mass revealed the three lymphoma types which were morphologically, immunophenotypically and topographically distinct. Fluorescence in situ hybridization (FISH) identified an IGH-BCL2 rearrangement in both the FL and high-grade B-cell components while a MYC rearrangement was detected in the high-grade B-cell component alone. CONCLUSIONS: Our findings suggest that the high-grade lymphoma with MYC and BCL2 translocations evolved through transformation of the FL by a process that entailed acquisition of the MYC translocation. No clonal relationship between the FL and CLL/SLL components was evident since the IGH-BCL2 rearrangement was present in in the former but not the latter. This unique case of co-localized FL, CLL/SLL, and high-grade B-cell lymphoma contributes to our understanding of the clonal relationships that may exist between the components of composite lymphomas. PMID- 29793521 TI - Substance-induced anxiety disorder after one dose of 3,4 methylenedioxymethamphetamine: a case report. AB - BACKGROUND: In this report, we describe a case of a patient with substance induced anxiety disorder occurring after a single dose of 3,4 methylenedioxymethamphetamine. Furthermore, we describe the use and efficacy of the Primary Care Behavioral Health model, a collaborative approach to integrative primary mental health care, in evaluating and treating this rare mental health disorder. CASE PRESENTATION: Three days following ingestion of one dose of 3,4 methylenedioxymethamphetamine, a 35-year-old Hispanic man with no significant prior mental health history and no history of prior 3,4 methylenedioxymethamphetamine use presented to our hospital with severe, acute anxiety and panic symptoms. He was initially treated with a combination of behavioral therapy and the serotonin agonist buspirone. Buspirone ultimately proved ineffective, so it was discontinued in favor of the selective serotonin reuptake inhibitor sertraline. While awaiting the pharmacological onset of sertraline, the patient worked with a behavioral health consultant, who provided psychoeducation on the experience of panic, building relaxation skills, and modifying maladaptive thought patterns. Enhanced communication between the primary care provider and behavioral health consultant facilitated the planning and enactment of the patient's care plan. Approximately 2.5 months after his initial ingestion of 3,4-methylenedioxymethamphetamine, the patient's symptoms subsided. This improvement was attributed to the combination of the behavioral health intervention and sertraline at a dose of 50 mg daily. Six months after 3,4 methylenedioxymethamphetamine ingestion, the patient began to gradually taper sertraline and has had no resurgence of anxiety symptoms to date. CONCLUSIONS: Our patient's case not only demonstrates a rare presentation of 3,4 methylenedioxymethamphetamine-induced anxiety disorder but also provides support for the use of the Primary Care Behavioral Health model to deliver individualized, timely mental health care in a primary care setting. PMID- 29793520 TI - De novo assembly and annotation of Hyalomma dromedarii tick (Acari: Ixodidae) sialotranscriptome with regard to gender differences in gene expression. AB - BACKGROUND: Hard ticks are hematophagous ectoparasites characterized by their long-term feeding. The saliva that they secrete during their blood meal is their crucial weapon against host-defense systems including hemostasis, inflammation and immunity. The anti-hemostatic, anti-inflammatory and immune-modulatory activities carried out by tick saliva molecules warrant their pharmacological investigation. The Hyalomma dromedarii Koch, 1844 tick is a common parasite of camels and probably the best adapted to deserts of all hard ticks. Like other hard ticks, the salivary glands of this tick may provide a rich source of many compounds whose biological activities interact directly with host system pathways. Female H. dromedarii ticks feed longer than males, thereby taking in more blood. To investigate the differences in feeding behavior as reflected in salivary compounds, we performed de novo assembly and annotation of H. dromedarii sialotranscriptome paying particular attention to variations in gender gene expression. RESULTS: The quality-filtered Illumina sequencing reads deriving from a cDNA library of salivary glands led to the assembly of 15,342 transcripts. We deduced that the secreted proteins included: metalloproteases, glycine-rich proteins, mucins, anticoagulants of the mandanin family and lipocalins, among others. Expression analysis revealed differences in the expression of transcripts between male and female H. dromedarii that might explain the blood-feeding strategies employed by both genders. CONCLUSIONS: The annotated sialome of H. dromedarii helps understand the interaction of tick-host molecules during blood feeding and can lead to the discovery of new pharmacologically active proteins of ticks of the genus Hyalomma. PMID- 29793523 TI - Financial hardship and drug use among men who have sex with men. AB - BACKGROUND: Little is known about the role of financial hardship as it relates to drug use, especially among men who have sex with men (MSM). As such, this study aimed to investigate potential associations between financial hardship status and drug use among MSM. METHODS: We conducted a cross-sectional survey of 580 MSM in Paris recruited using a popular geosocial-networking smartphone application (GSN apps). Descriptive analyses and multivariate analyses were performed. A modified Poisson model was used to assess associations between financial hardship status and use of drugs (any drugs, tobacco, alcohol, marijuana, inhalant nitrites, and club drugs). RESULTS: In our sample, 45.5% reported that it was somewhat, very, or extremely difficult to meet monthly payments of bills (high financial hardship). In multivariate analyses, a high level of financial hardship was significantly associated with an increased likelihood of reporting use of any substance use (adjusted risk ratio [aRR] = 1.15; 95% CI = 1.05-1.27), as well as use of tobacco (aRR = 1.45; 95% CI = 1.19-1.78), marijuana (aRR = 1.48; 95% CI =1.03-2.13), and inhalant nitrites (aRR = 1.24; 95% CI = 1.03-1.50). CONCLUSIONS: Financial hardship was associated with drug use among MSM, suggesting the need for interventions to reduce the burden of financial hardship in this population. PMID- 29793522 TI - Older adult's experience of chronic low back pain and its implications on their daily life: Study protocol of a systematic review of qualitative research. AB - BACKGROUND: Of various chronic diseases, low back pain (LBP) is the most common and debilitating musculoskeletal condition among older adults aged 65 years or older. While more than 17 million older adults in the USA suffer from at least one episode of LBP annually, approximately six million of them experience chronic LBP that significantly affects their quality of life and physical function. Since many older adults with chronic LBP may also have comorbidities and are more sensitive to pain than younger counterparts, these older individuals may face unique age-related physical and psychosocial problems. While some qualitative research studies have investigated the life experiences of older adults with chronic LBP, no systematic review has integrated and synthesized the scientific knowledge regarding the influence of chronic LBP on the physical, psychological, and social aspects of lives in older adults. Without such information, it may result in unmet care needs and ineffective interventions for this vulnerable group. Therefore, the objective of this systematic review is to synthesize knowledge regarding older adults' experiences of living with chronic LBP and the implications on their daily lives. METHODS/DESIGN: Candidate publications will be sought from databases: PubMed, CINAHL, and PsycINFO. Qualitative research studies will be included if they are related to the experiences of older adults with chronic LBP. Two independent reviewers will screen the titles, abstracts, and full-text articles for eligibility. The reference lists of the included studies will be checked for additional relevant studies. Forward citation tracking will be conducted. Meta-ethnography will be chosen to synthesize the data from the included studies. Specifically, the second-order concepts that are deemed to be translatable by two independent reviewers will be included and synthesized to capture the core of the idiomatic translations (i.e., a translation focusing on salient categories of meaning rather than the literal translation of words or phrases). DISCUSSION: This systematic review of qualitative evidence will enable researchers to identify potential unmet care needs, as well as to facilitate the development of effective, appropriate, person-centered health care interventions targeting this group of individuals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018: CRD42018091292. PMID- 29793524 TI - A central-acting connexin inhibitor, INI-0602, prevents high-fat diet-induced feeding pattern disturbances and obesity in mice. AB - A high-fat diet (HFD) causes obesity by promoting excessive energy intake, and simultaneously, by disturbing the timing of energy intake. Restoring the feeding pattern is sufficient to prevent HFD-induced obesity in mice. However, the molecular mechanism(s) underlying HFD-induced feeding pattern disturbances remain elusive. Saturated fatty acids activate microglia and cause hypothalamic inflammation. Activated microglia cause neuroinflammation, which spreads via inflammatory cytokines and gap-junction hemichannels. However, the role of gap junction hemichannels in HFD-induced obesity remains unaddressed. We used a novel, central-acting connexin inhibitor, INI-0602, which has high affinity for gap junction hemichannels and does not affect the induction of inflammatory cytokines. We analyzed ad libitum feeding behavior and locomotor activity in mice that were fed normal chow (NC), a HFD with elevated saturated fatty acids (SFAs), or a HFD with very high SFAs. We found that HFD feeding induced acute hyperphagia, mainly during the light cycle. Feeding pattern disturbances were more pronounced in mice that consumed the HFD with very high SFAs than in mice that consumed the HFD with elevated SFAs. When INI-0602 was administered before the HFD was introduced, it blocked the feeding pattern disturbance, but not locomotor activity disturbances; moreover, it prevented subsequent diet-induced obesity. However, when INI-0602 was administered after the HFD had disturbed the feeding pattern, it failed to restore the normal feeding pattern. Therefore, we propose that SFAs in HFDs played a major role in disrupting feeding patterns in mice. Moreover, the feeding pattern disturbance required the function of central, gap junction hemichannels at the initiation of a HFD. However, altering hemichannel function after the feeding pattern disturbance was established had no effect. Thus, preventing the occurrence of a feeding pattern disturbance by blocking the hemichannel pathway was associated with the prevention of the HFD induced obesity in mice. PMID- 29793526 TI - Comparing population and incident data for optimal air ambulance base locations in Norway. AB - BACKGROUND: Helicopter emergency medical services are important in many health care systems. Norway has a nationwide physician manned air ambulance service servicing a country with large geographical variations in population density and incident frequencies. The aim of the study was to compare optimal air ambulance base locations using both population and incident data. METHODS: We used municipality population and incident data for Norway from 2015. The 428 municipalities had a median (5-95 percentile) of 4675 (940-36,264) inhabitants and 10 (2-38) incidents. Optimal helicopter base locations were estimated using the Maximal Covering Location Problem (MCLP) optimization model, exploring the number and location of bases needed to cover various fractions of the population for time thresholds 30 and 45 min, in green field scenarios and conditioned on the existing base structure. RESULTS: The existing bases covered 96.90% of the population and 91.86% of the incidents for time threshold 45 min. Correlation between municipality population and incident frequencies was -0.0027, and optimal base locations varied markedly between the two data types, particularly when lowering the target time. The optimal solution using population density data put focus on the greater Oslo area, where one third of Norwegians live, while using incident data put focus on low population high incident areas, such as northern Norway and winter sport resorts. CONCLUSION: Using population density data as a proxy for incident frequency is not recommended, as the two data types lead to different optimal base locations. Lowering the target time increases the sensitivity to choice of data. PMID- 29793525 TI - Inhibitor analysis revealed that clathrin-mediated endocytosis is involed in cellular entry of type III grass carp reovirus. AB - BACKGROUND: Grass carp (Ctenopharyngodon idella) hemorrhagic disease is caused by an acute infection with grass carp reovirus (GCRV). The frequent outbreaks of this disease have suppressed development of the grass carp farming industry. GCRV104, the representative strain of genotype III grass carp (Ctenopharyngodon idella) reovirus, belongs to the Spinareovirinae subfamily and serves as a model for studying the strain of GCRV which encodes an outer-fiber protein. There is no commercially available vaccine for this genotype of GCRV. Therefore, the discovery of new inhibitors for genotype III of GCRV will be clinically beneficial. In addition, the mechanism of GCRV with fiber entry into cells remains poorly understood. METHODS: Viral entry was determined by a combination of specific pharmacological inhibitors, transmission electron microscopy, and real-time quantitative PCR. RESULTS: Our results demonstrate that both GCRV-JX01 (genotype I) and GCRV104 (genotype III) of GCRV propagated in the grass carp kidney cell line (CIK) with a typical cytopathic effect (CPE). However, GCRV104 replicated slower than GCRV-JX01 in CIK cells. The titer of GCRV-JX01 was 1000 times higher than GCRV104 at 24 h post-infection. We reveal that ammonium chloride, dynasore, pistop2, chlorpromazine, and rottlerin inhibit viral entrance and infection, but not nystatin, methyl-beta-cyclodextrin, IPA-3, amiloride, bafilomycin A1, nocodazole, and latrunculin B. Furthermore, GCRV104 and GCRV-JX01 infection of CIK cells depended on dynamin and the acidification of the endosome. This was evident by the significant inhibition following prophylactic treatment with the lysosomotropic drug ammonium chloride or dynasore. CONCLUSIONS: Taken together, our data have suggested that GCRV104 enters CIK cells through clathrin mediated endocytosis in a pH-dependent manner. We also suggest that dynamin is critical for efficient viral entry. Additionally, the phosphatidylinositol 3 kinase inhibitor wortmannin and the protein kinase C inhibitor rottlerin block GCRV104 cell entry and replication. PMID- 29793527 TI - Impact of preoperative patient education on the prevention of postoperative complications after major visceral surgery: the cluster randomized controlled PEDUCAT trial. AB - BACKGROUND: The prevention of postoperative complications is of prime importance after complex elective abdominal operations. Preoperative patient education may prevent postoperative complications and improve patients' wellbeing, but evidence for its efficacy is poor. The aims of the PEDUCAT trial were (a) to assess the impact of preoperative patient education on postoperative complications and patient-reported outcomes in patients scheduled for elective complex visceral surgery and (b) to evaluate the feasibility of cluster randomization in this setting. METHODS: Adult patients (age >= 18 years) scheduled for elective major visceral surgery were randomly assigned in clusters to attend a preoperative education seminar or to the control group receiving the department's standard care. Outcome measures were the postoperative complications pneumonia, deep vein thrombosis (DVT), pulmonary embolism, burst abdomen, and in-hospital fall, together with patient-reported outcomes (postoperative pain, anxiety and depression, patient satisfaction, quality of life), length of hospital stay (LOS), and postoperative mortality within 30 days after the index operation. Statistical analysis was primarily by intention to treat. RESULTS: In total 244 patients (60 clusters) were finally included (intervention group 138 patients; control group 106 patients). Allocation of hospital wards instead of individual patients facilitated study conduct and reduced confusion about group assignment. In the intervention and control groups respectively, pneumonia occurred in 7.4% versus 8.3% (p = 0.807), pulmonary embolism in 1.6% versus 1.0% (p = 0.707), burst abdomen in 4.2% versus 1.0% (p = 0.165), and in-hospital falls in 0.0% versus 4.2% of patients (p = 0.024). DVT did not occur in any of the patients. Mortality rates (1.4% versus 1.9%, p = 0.790) and LOS (14.2 (+/- 12.0) days versus 16.1 (+/- 15.0) days, p = 0.285) were also similar in the intervention and control groups. CONCLUSIONS: Cluster randomization was feasible in the setting of preoperative patient education and reduced the risk of contamination effects. The results of this trial indicate good postoperative outcomes in patients undergoing major visceral surgery without superiority of preoperative patient education compared to standard patient care at a high-volume center. However, preoperative patient education is a helpful instrument not only for teaching patients but also for training the nursing staff. TRIAL REGISTRATION: German Clinical Trials Registry, DRKS00004226 . Registered on 23 October 2012. Registered 8 days after the first enrollment. PMID- 29793528 TI - Prevalence of anemia among school-age children in Ethiopia: a systematic review and meta-analysis. AB - BACKGROUND: Anemia continued to become a major public health problem in developing nations including Ethiopia. Especially, school children are more vulnerable for anemia and consequences of anemia. Generating accurate epidemiological data on anemia in school children is an important step for health policy maker. There are limited evidences on anemia prevalence in school-age children in Ethiopia. This study aimed to synthesize the pooled prevalence of anemia in school-age children in Ethiopia. METHODS: This systematic review and meta-analysis was followed the PRISMA guidelines. Comprehensive searched was conducted in PubMed/MEDLINE, Cochrane Library, Google Scholar, HINARI, and Ethiopian Journal of Health Development for studies published before 2016, supplemented by manual searches to identify relevant studies. Two review authors independently selected studies, extracted data, and assessed quality of studies. The Cochrane Q test and I2 test statistic were used to test heterogeneity through studies. The overall prevalence was calculated using random-effects model of DerSimonian-Laird method. RESULTS: From 831 obtained studies, 13 articles included in the meta-analysis. The pooled prevalence of anemia among school children in Ethiopia was 23% (95% CI 18-28%). The prevalence of anemia in male and female school-age children was 27% (95% CI 20 and 34%) and 24% (95% CI 18 and 30%), respectively. CONCLUSIONS: This study found that prevalence of anemia was a moderate public health problem in school children. Due to the complications of anemia for school children, preventative planning and control of anemia among school children in Ethiopia is necessary. PMID- 29793529 TI - Effects of lifetime cumulative ginseng intake on cognitive function in late life. AB - BACKGROUND: We investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders. METHODS: Community-dwelling elders (N = 6422; mean age = 70.2 +/- 6.9 years, education = 8.0 +/- 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among them, 3918 participants (61.0%) completed the 2-year and 4-year follow-up evaluations. Subjects were categorized according to cumulative ginseng intake at baseline evaluation; no use group, low use (< 5 years) group, and high use (>= 5 years) group. One-way analysis of covariance (ANCOVA) was conducted to compare the impact of cumulative ginseng intake on baseline Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet neuropsychological battery total score (CERAD total score) and Mini-Mental State Examination (MMSE) score among the three groups while adjusting for potential covariates. A repeated measures ANCOVA was performed to investigate the impacts on the changes in CERAD total scores and MMSE scores during the 4 years of follow-up. RESULTS: The high use group showed higher CERAD total scores compared to the no use group after controlling for age, sex, education years, socioeconomic status, smoking, alcohol intake, presence of hypertension, stroke history, Geriatric Depression Scale, Cumulative Illness Rating Scale, and presence of the APOE e4 allele (F(2, 4762) = 3.978, p = 0.019). The changes of CERAD total score for 2 or 4 years of follow-up did not differ according to the use of ginseng. CONCLUSIONS: Cumulative ginseng use for longer than 5 years may be beneficial to cognitive function in late life. PMID- 29793530 TI - Efficient clearance of Abeta protofibrils in AbetaPP-transgenic mice treated with a brain-penetrating bifunctional antibody. AB - BACKGROUND: Amyloid-beta (Abeta) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Despite recent progress targeting aggregated forms of Abeta, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR) mediated transcytosis to facilitate brain uptake of our previously developed Abeta protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble Abeta protofibrils. METHODS: Abeta protein precursor (AbetaPP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFv8D3), in comparison with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158). Soluble Abeta protofibrils and total Abeta in the brain were measured by enzyme-linked immunosorbent assay (ELISA). Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoradiography. RESULTS: ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble Abeta protofibrils in both RmAb158 scFv8D3- and high-dose RmAb158-treated mice, whereas there was no Abeta protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed different brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect Abeta levels by different mechanisms. CONCLUSIONS: With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood-brain barrier can be used to increase the efficacy of Abeta immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs. PMID- 29793533 TI - Clinical effect of selective interventional therapy on sub-acute ST-segment elevation myocardial infarction under the guidance of fractional flow reserve and coronary arteriography. AB - OBJECTIVE: This study aims to compare the clinical effects of selective interventional therapy (PCI) under the guidance of fractional flow reserve (FFR) and coronary arteriography. METHODS: Patients with sub-acute ST-segment elevation myocardial infarction (sub-acute STEMI), who were under selective PCI treatment between April 2012 and June 2014, were included into this study. These patients were divided into two groups, based on FFR measurements: FFR-PCI group and radiography-PCI group. Then, differences in clinical symptoms, coronary angiography, intervention, and endpoint events were compared between these two groups. RESULTS: A total of 592 patients with sub-acute STEMI were included in this study (207 patients in the FFR-PCI group and 385 patients in the radiography PCI group). No statistical differences were observed in baseline clinical data and coronary angiography results between these two groups. Mean stent number was greater in the radiography-PCI group (1.22 +/- 0.32) than in the FFR-PCI group (1.10 +/- 0.29), and the difference was statistically significant (P = 0.019). During the follow-up period, 78 adverse events occurred (21 adverse events in the FFR-PCI group and 57 adverse events in the radiography-PCI group); and no statistical significance was observed between these two groups (log-rank P = 0.112). CONCLUSION: Selective PCI treatment in patients with sub-acute STEMI under FFR acquired similar effects, compared to PCI treatment under the guidance of radiography, which can reduce the mean stent number. PMID- 29793531 TI - Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota. AB - BACKGROUND: The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes. RESULTS: Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding. CONCLUSIONS: Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome. PMID- 29793534 TI - Integrating rare genetic variants into pharmacogenetic drug response predictions. AB - BACKGROUND: Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common genetic polymorphisms, recent sequencing projects revealed a plethora of rare genetic variants in genes encoding proteins involved in drug metabolism, transport, and response. RESULTS: To understand the global importance of rare pharmacogenetic gene variants, we mapped the variability in 208 pharmacogenes by analyzing exome sequencing data from 60,706 unrelated individuals and estimated the importance of rare and common genetic variants using a computational prediction framework optimized for pharmacogenetic assessments. Our analyses reveal that rare pharmacogenetic variants were strongly enriched in mutations predicted to cause functional alterations. For more than half of the pharmacogenes, rare variants account for the entire genetic variability. Each individual harbored on average a total of 40.6 putatively functional variants, rare variants accounting for 10.8% of these. Overall, the contribution of rare variants was found to be highly gene- and drug-specific. Using warfarin, simvastatin, voriconazole, olanzapine, and irinotecan as examples, we conclude that rare genetic variants likely account for a substantial part of the unexplained inter-individual differences in drug metabolism phenotypes. CONCLUSIONS: Combined, our data reveal high gene and drug specificity in the contributions of rare variants. We provide a proof-of-concept on how this information can be utilized to pinpoint genes for which sequencing-based genotyping can add important information to predict drug response, which provides useful information for the design of clinical trials in drug development and the personalization of pharmacological treatment. PMID- 29793532 TI - The contribution of culturomics to the repertoire of isolated human bacterial and archaeal species. AB - After a decade of research and metagenomic analyses, our knowledge of the human microbiota appears to have reached a plateau despite promising results. In many studies, culture has proven to be essential in describing new prokaryotic species and filling metagenomic gaps. In 2015, only 2172 different prokaryotic species were reported to have been isolated at least once from the human body as pathogens or commensals. In this review, we update the previous repertoire by reporting the different species isolated from the human body to date, increasing it by 28% to reach a total of 2776 species associated with human beings. They have been classified into 11 different phyla, mostly the Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. Finally, culturomics contributed up to 66.2% towards updating this repertoire by reporting 400 species, of which 288 were novel. This demonstrates the need to continue the culturing work, which seems essential in order to decipher the hidden human microbial content. PMID- 29793535 TI - Limitations in clinical outcome after posterior stabilization of thoracolumbar fractures do not correlate with dynamic trunk muscle dysfunction: an ultrasound controlled prospective cohort study. AB - BACKGROUND AND PURPOSE: Posterior stabilization of the spine is associated with iatrogenic muscle damage. This is discussed to represent an important cause of postoperative pain, especially in open reduction and fixation. The aim of this study was to visualize muscular changes after open or percutaneous posterior stabilization of traumatic thoracolumbar spine fractures and to investigate whether or not these changes are related to the clinical outcome. METHODS: This prospective cohort study was performed between 05/2012 and 10/2014. A group of posteriorly stabilized patients (study group; SG) with traumatic fractures (AOSpine Type A3 or A4) of the thoracolumbar junction (T11-L2) without neurological deficit were matched to a healthy control group (CG) by age, gender and body mass index. FOLLOW-UP: 12 months after surgery. PARAMETERS: muscle size, voluntary muscular activation (VMA) using a standardized ultrasound protocol and standardized questionnaires (VAS Spine Score; ODI; SF-36) were analyzed. STATISTICS: SPSS (Version 20, 76 Chicago, IL, USA). T test, Chi squared test, analysis of variance and a correlation analysis were performed. Significance level was at p < 0.05. RESULTS: Twenty-five patients (SG) and 23 control individuals (CG) were included. At follow-up, voluntary muscular activation of the lumbar multifidus (LM) as well as the transverse abdominis muscle (TrA) was diminished in all patients compared to the control group (VMA LM at level L3/4: SG 3.2%; CG 5.1%; p < 0.05; VMA TrA: SG 33.43%; CG 37.84%; p < 0.05). Concomitant interviews revealed health restrictions in all patients when compared with the control group. A correlation between muscle function and clinical outcome could not been demonstrated (rs > 0.07; NS). CONCLUSION: In surgically treated A3 and A4 fractures, there is continuous muscular deficit 1 year after surgery as documented by ultrasound and clinical control. But, by means of our study we conclude that those muscular deficits alone seem not to be decisive for the clinical outcome 1 year after surgery. PMID- 29793536 TI - Risk classification of patients referred to secondary care for low back pain. AB - BACKGROUND: Nonspecific low back pain is characterized by a wide range of possible triggering and conserving factors, and initial screening needs to scope widely with multilevel addressment of possible factors contributing to the pain experience. Screening tools for classification of patients have been developed to support clinicians. The primary aim of this study was to assess the criterion validity of STarT Back Screening Tool (STarT Back) against the more comprehensive Orebro Musculoskeletal Pain Questionnaire (OMPSQ), in a Norwegian sample of patients referred to secondary care for low back pain. Secondary aims were to assess risk classification of the patients, as indicated by both instruments, and to compare pain and work characteristics between patients in the different STarT Back risk categories. METHODS: An observational, cross-sectional survey among patients with low back pain referred to outpatient secondary care assessment at Trondheim University Hospital, Norway. Cohen's Kappa coefficient, Pearson's r and a Bland-Altman plot were used to assess criterion validity of STarT Back against OMPSQ. Furthermore, linear regression was used to estimate mean differences with 95% CI in pain and work related variables between the risk groups defined by the STarT Back tool. RESULTS: A total of 182 persons participated in the study. The Pearsons correlation coefficient for correspondence between scores on OMPSQ and STarT Back was 0.76. The Kappa value for classification agreement between the instruments was 0.35. Risk group classification according to STarT Back allocated 34.1% of the patients in the low risk group, 42.3% in the medium risk, and 23.6% in the high risk group. According to OMPSQ, 24.7% of the participants were allocated in the low risk group, 28.6% in the medium risk, and 46.7% in the high risk group. Patients classified with high risk according to Start Back showed a higher score on pain and work related characteristics as measured by OMPSQ. CONCLUSION: The correlation between score on the screening tools was good, while the classification agreement between the screening instruments was low. Screening for work factors may be important in patients referred to multidisciplinary management in secondary care. PMID- 29793537 TI - Genetic contribution to mesenchymal stem cell dysfunction in systemic lupus erythematosus. AB - Allogeneic mesenchymal stem cell (MSC) transplantation has recently become a promising therapy for patients with systemic lupus erythematosus (SLE). MSCs are a kind of multipotent stem cell than can efficiently modulate both innate and adaptive immune responses, yet those from SLE patients themselves fail to maintain the balance of immune cells, which is partly due to the abnormal genetic background. Clarifying genetic factors associated with MSC dysfunction may be helpful to delineate SLE pathogenesis and provide new therapeutic targets. In this review, the scientific evidence on the genetic contribution to MSC dysfunction in SLE is summarized. PMID- 29793538 TI - MicroRNA-1247 inhibits cell proliferation by directly targeting ZNF346 in childhood neuroblastoma. AB - BACKGROUND: Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro. METHODS/RESULTS: We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be downregulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells. CONCLUSIONS: Our findings suggested miR 1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB. PMID- 29793539 TI - Gut microbes contribute to variation in solid organ transplant outcomes in mice. AB - BACKGROUND: Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. RESULTS: We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. CONCLUSIONS: These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT. PMID- 29793541 TI - Translating research into action: an international study of the role of research funders. AB - BACKGROUND: It is widely accepted that research can lead to improved health outcomes. However, translating research into meaningful impacts in peoples' lives requires actions that stretch well beyond those traditionally associated with knowledge creation. The research reported in this manuscript provides an international review of health research funders' efforts to encourage this process of research uptake, application and scaling, often referred to as knowledge translation. METHODS: We conducted web-site review, document review and key informant interviews to investigate knowledge translation at 26 research funding agencies. The sample comprises the regions of Australia, Europe and North America, and a diverse range of funder types, including biomedical, clinical, multi-health domain, philanthropic, public and private organisations. The data builds on a 2008 study by the authors with the same international sample, which permitted longitudinal trend analysis. RESULTS: Knowledge translation is an objective of growing significance for funders across each region studied. However, there is no clear international consensus or standard on how funders might support knowledge translation. We found that approaches and mechanisms vary across region and funder type. Strategically tailored funding opportunities (grants) are the most prevalent modality of support. The most common funder driven strategy for knowledge translation within these grants is the linking of researchers to research users. Funders could not to provide empirical evidence to support the majority of the knowledge translation activities they encourage or undertake. CONCLUSIONS: Knowledge translation at a research funder relies on context. Accordingly, we suggest that the diversity of approaches uncovered in our research is fitting. We argue that evaluation of funding agency efforts to promote and/or support knowledge translation should be prioritised and actioned. It is paradoxical that funders' efforts to get evidence into practice are not themselves evidence based. PMID- 29793540 TI - A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial. AB - BACKGROUND: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011. However, study start-up was significantly delayed and recruitment did not start until January 2013. METHOD: The FOR-DMD study is used as an example to identify systematic problems in the set-up of international, multi-centre clinical trials. The full timeline of the FOR-DMD study, from funding approval to site activation, was collated and reviewed. Systematic issues were identified and grouped into (1) study set-up, e.g. drug procurement; (2) country set-up, e.g. competent authority applications; and (3) site set-up, e.g. contracts, to identify the main causes of delay and suggest areas where anticipatory action could overcome these obstacles in future studies. RESULTS: Time from the first contact to site activation across countries ranged from 6 to 24 months. Reasons of delay were universal (sponsor agreement, drug procurement, budgetary constraints), country specific (complexity and diversity of regulatory processes, indemnity requirements) and site specific (contracting and approvals). The main identified obstacles included (1) issues related to drug supply, (2) NIH requirements regarding contracting with non-US sites, (3) differing regulatory requirements in the five participating countries, (4) lack of national harmonisation with contracting and the requirement to negotiate terms and contract individually with each site and (5) diversity of languages needed for study materials. Additionally, as with many academic-led studies, the FOR-DMD study did not have access to the infrastructure and expertise that a contracted research organisation could provide, organisations often employed in pharmaceutical-sponsored studies. This delay impacted recruitment, challenged the clinical relevance of the study outcomes and potentially delayed the delivery of the best treatment to patients. CONCLUSION: Based on the FOR-DMD experience, and as an interim solution, we have devised a checklist of steps to not only anticipate and minimise delays in academic international trial initiation but also identify obstacles that will require a concerted effort on the part of many stakeholders to mitigate. PMID- 29793542 TI - Tracking antibiotic resistance gene pollution from different sources using machine-learning classification. AB - BACKGROUND: Antimicrobial resistance (AMR) has been a worldwide public health concern. Current widespread AMR pollution has posed a big challenge in accurately disentangling source-sink relationship, which has been further confounded by point and non-point sources, as well as endogenous and exogenous cross-reactivity under complicated environmental conditions. Because of insufficient capability in identifying source-sink relationship within a quantitative framework, traditional antibiotic resistance gene (ARG) signatures-based source-tracking methods would hardly be a practical solution. RESULTS: By combining broad-spectrum ARG profiling with machine-learning classification SourceTracker, here we present a novel way to address the question in the era of high-throughput sequencing. Its potential in extensive application was firstly validated by 656 global-scale samples covering diverse environmental types (e.g., human/animal gut, wastewater, soil, ocean) and broad geographical regions (e.g., China, USA, Europe, Peru). Its potential and limitations in source prediction as well as effect of parameter adjustment were then rigorously evaluated by artificial configurations with representative source proportions. When applying SourceTracker in region-specific analysis, excellent performance was achieved by ARG profiles in two sample types with obvious different source compositions, i.e., influent and effluent of wastewater treatment plant. Two environmental metagenomic datasets of anthropogenic interference gradient further supported its potential in practical application. To complement general-profile-based source tracking in distinguishing continuous gradient pollution, a few generalist and specialist indicator ARGs across ecotypes were identified in this study. CONCLUSION: We demonstrated for the first time that the developed source-tracking platform when coupling with proper experiment design and efficient metagenomic analysis tools will have significant implications for assessing AMR pollution. Following predicted source contribution status, risk ranking of different sources in ARG dissemination will be possible, thereby paving the way for establishing priority in mitigating ARG spread and designing effective control strategies. PMID- 29793543 TI - Prevalence and determinants of essential newborn care practices in the Lawra District of Ghana. AB - BACKGROUND: There was less than satisfactory progress, especially in sub-Saharan Africa, towards child and maternal mortality targets of Millennium Development Goals (MDGs) 4 and 5. The main aim of this study was to describe the prevalence and determinants of essential new newborn care practices in the Lawra District of Ghana. METHODS: A cross-sectional study was carried out in June 2014 on a sample of 422 lactating mothers and their children aged between 1 and 12 months. A systematic random sampling technique was used to select the study participants who attended post-natal clinic in the Lawra district hospital. RESULTS: Of the 418 newborns, only 36.8% (154) was judged to have had safe cord care, 34.9% (146) optimal thermal care, and 73.7% (308) were considered to have had adequate neonatal feeding. The overall prevalence of adequate new born care comprising good cord care, optimal thermal care and good neonatal feeding practices was only 15.8%. Mothers who attained at least Senior High Secondary School were 20.5 times more likely to provide optimal thermal care [AOR 22.54; 95% CI (2.60-162.12)], compared to women had no formal education at all. Women who received adequate ANC services were 4.0 times (AOR = 4.04 [CI: 1.53, 10.66]) and 1.9 times (AOR = 1.90 [CI: 1.01, 3.61]) more likely to provide safe cord care and good neonatal feeding as compared to their counterparts who did not get adequate ANC. However, adequate ANC services was unrelated to optimal thermal care. Compared to women who delivered at home, women who delivered their index baby in a health facility were 5.6 times more likely of having safe cord care for their babies (AOR = 5.60, Cl: 1.19-23.30), p = 0.03. CONCLUSIONS: The coverage of essential newborn care practices was generally low. Essential newborn care practices were positively associated with high maternal educational attainment, adequate utilization of antenatal care services and high maternal knowledge of newborn danger signs. Therefore, greater improvement in essential newborn care practices could be attained through proven low-cost interventions such as effective ANC services, health and nutrition education that should span from community to health facility levels. PMID- 29793544 TI - Consistency of health-related quality of life among people living with HIV: Latent statetrait analysis. AB - BACKGROUND: The aim of this longitudinal study was to examine the consistency of health-related quality of life (HRQoL) among people living with HIV (PLWH) by breaking down the variance of repeated HRQoL measures into trait, state, and method components and to test the stability of HRQoL over time. In addition, we wanted to examine whether HRQoL trait components are related to personality traits, while controlling for selected socio-medical variables. METHODS: Three assessments were performed with a six-month lag on each assessment. Each participant filled out a World Health Organization (WHO) Quality of Life-BREF to assess HRQoL and a NEO-FFI to measure Big Five personality traits. Overall, 82 participants out of 141 (58.2% of the initial sample) participated in all the assessments. RESULTS: The HRQoL among PLWH represented a stable trait to a somewhat greater extent than a situational variability, although the proportions were domain and time variant. More specifically, psychological domain appeared to be the most consistent, whereas social domain appeared to be the most prone to situational influences. The trait component of HRQoL was positively related to being in a relationship, being employed, and being extraverted, and negatively related to neuroticism, which altogether explained 26% of the trait variance. CONCLUSIONS: HRQoL among PLWH is rather distinct from personality and socio medical data, which indicates its uniqueness in a clinical practise. Thus, there is a need for a more comprehensive assessment of HRQoL among this patient group to capture an additional source of variance in this important theoretical construct. PMID- 29793545 TI - White matter microstructure is altered in cognitively normal middle-aged APOE epsilon4 homozygotes. AB - BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) is the strongest genetic factor for late-onset Alzheimer's disease. During middle age, cognitively healthy APOE-epsilon4 carriers already show several brain alterations that resemble those of Alzheimer's disease (AD), but to a subtler degree. These include microstructural white matter (WM) changes that have been proposed as one of the earliest structural events in the AD cascade. However, previous studies have focused mainly on comparison of APOE-epsilon4 carriers vs noncarriers. Therefore, the extent and magnitude of the brain alterations in healthy epsilon4 homozygotes, who are the individuals at highest risk, remain to be characterized in detail. METHODS: We examined mean, axial, and radial water diffusivity (MD, AxD, and RD, respectively) and fractional anisotropy in the WM as measured by diffusion-weighted imaging in 532 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-epsilon4 homozygotes, 207 heterozygotes, and 257 noncarriers). We examined the impact of age and APOE genotype on these parameters using tract-based spatial statistics. RESULTS: Healthy APOE-epsilon4 homozygotes display increased WM diffusivity in regions known to be affected by AD. The effects in AxD were much smaller than in RD, suggesting a disruption of the myelin sheath rather than pure axonal damage. CONCLUSIONS: These findings could be interpreted as the result of the reduced capacity of the epsilon4 isoform of the APOE protein to keep cholesterol homeostasis in the brain. Because cerebral lipid metabolism is strongly related to the pathogenesis of AD, our results shed light on the possible mechanisms through which the APOE-epsilon4 genotype is associated with an increased risk of AD. PMID- 29793546 TI - Distinct patterns of brain atrophy in Genetic Frontotemporal Dementia Initiative (GENFI) cohort revealed by visual rating scales. AB - BACKGROUND: In patients with frontotemporal dementia, it has been shown that brain atrophy occurs earliest in the anterior cingulate, insula and frontal lobes. We used visual rating scales to investigate whether identifying atrophy in these areas may be helpful in distinguishing symptomatic patients carrying different causal mutations in the microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame (C9ORF72) genes. We also analysed asymptomatic carriers to see whether it was possible to visually identify brain atrophy before the appearance of symptoms. METHODS: Magnetic resonance imaging of 343 subjects (63 symptomatic mutation carriers, 132 presymptomatic mutation carriers and 148 control subjects) from the Genetic Frontotemporal Dementia Initiative study were analysed by two trained raters using a protocol of six visual rating scales that identified atrophy in key regions of the brain (orbitofrontal, anterior cingulate, frontoinsula, anterior and medial temporal lobes and posterior cortical areas). RESULTS: Intra- and interrater agreement were greater than 0.73 for all the scales. Voxel-based morphometric analysis demonstrated a strong correlation between the visual rating scale scores and grey matter atrophy in the same region for each of the scales. Typical patterns of atrophy were identified: symmetric anterior and medial temporal lobe involvement for MAPT, asymmetric frontal and parietal loss for GRN, and a more widespread pattern for C9ORF72. Presymptomatic MAPT carriers showed greater atrophy in the medial temporal region than control subjects, but the visual rating scales could not identify presymptomatic atrophy in GRN or C9ORF72 carriers. CONCLUSIONS: These simple-to-use and reproducible scales may be useful tools in the clinical setting for the discrimination of different mutations of frontotemporal dementia, and they may even help to identify atrophy prior to onset in those with MAPT mutations. PMID- 29793547 TI - Long noncoding RNA AFAP1-AS1 predicts a poor prognosis and regulates non-small cell lung cancer cell proliferation by epigenetically repressing p21 expression. AB - BACKGROUND: Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the role and molecular mechanism and global genes that were mediated by lncRNA AFAP1-AS1 in non-small cell lung cancer (NSCLC) remain largely unknown. METHODS: Expression of AFAP1-AS1 was analyzed in 92 NSCLC tissues and cell lines by Quantitative real time polymerase chain reaction (qRT-PCR). The effect of AFAP1-AS1 on proliferation was evaluated by function assays both in in vitro and in vivo. RNA-seq assays were performed after knockdown AFAP1-AS1. RNA immunoprecipitation (RIP) was performed to confirm the interaction between AFAP1-AS1 and EZH2. Chromatin immunoprecipitation (ChIP) was used to study the promoter region of p21. RESULTS: AFAP1-AS1 expression was increased in NSCLC tissues and was correlated with clinical outcomes of NSCLC. Further experiments revealed that inhibition of its expression in NSCLC cells resulted in diminished cell growth in vitro and in vivo. RNA-seq revealed that knockdown of AFAP1-AS1 could induce the expression of p21. Mechanistic investigations found that AFAP1-AS1 could interact with EZH2 and recruit EZH2 to the promoter regions of p21, thus epigenetically repressing p21 expression. CONCLUSIONS: Together, these results suggest that lncRNA AFAP1-AS1 may serve as a candidate prognostic biomarker and target for new therapies in human NSCLC. PMID- 29793548 TI - Management of undescended testis may be improved with educational updates and new transferring model. AB - BACKGROUND: To investigate whether management of undescended testis (UDT) may be improved with educational updates and new transferring model among referring providers (RPs). METHODS: The age of orchidopexies performed in Children's Hospital of Chongqing Medical University were reviewed. We then proposed educational updates and new transferring model among RPs. The age of orchidopexies performed after our intervention were collected. Data were represented graphically and statistical analysis Chi-square for trend were used. RESULTS: A total of 1543 orchidopexies were performed. The median age of orchidopexy did not matched the target age of 6-12 months in any subsequent year. Survey of the RPs showed that 48.85% of their recommended age was below 12 months. However, only 25.50% of them would directly make a surgical referral to pediatric surgery specifically at this point. After we proposed educational updates, tracking the age of orchidopexy revealed a statistically significant trend downward. CONCLUSIONS: The management of undescended testis may be improved with educational updates and new transferring model among primary healthcare practitioners. PMID- 29793550 TI - The effects of ipsilateral tilt position on right subclavian venous catheterization: study protocol for a prospective randomized trial. AB - BACKGROUND: The cross-sectional area of the subclavian vein (csSCV) is an important factor determining the success rate of SCV catheterization. The head down position increases the csSCV. However, the effects of lateral tilting on subclavian venous cross-sectional area have not yet been explored. In this trial, we test our hypothesis that ipsilateral tilt during right SCV catheterization may significantly increase the csSCV by impeding blood flow to the heart, thereby increasing the primary venipuncture success rate and reducing the complication rate and procedure time. METHODS/DESIGN: This is a two-staged, prospective, randomized, controlled trial conducted on 237 neurosurgical patients requiring SCV catheterization. Seventeen patients in stage I will be placed in supine, 20 degrees ipsilateral tilt, and 20 degrees contralateral tilt positions in random order. The right csSCV will be measured using ultrasonography at each position. In stage II, 220 patients will be randomly assigned to the ipsilateral tilt group (n = 110) and supine group (n = 110) according to the position for right SCV catheterization. Data on catheterization-related characteristics and complications will be collected during and after catheterization. The primary outcome measures are the right csSCV for stage I and primary venipuncture success rate for stage II. The secondary outcome measures for stage II are time to venipuncture, total catheterization time, first-pass success rate, and complications, such as arterial puncture, hematoma, pneumothorax, air embolism, and catheter misplacement. DISCUSSION: This is the first trial to investigate the effects of the ipsilateral tilt position on right SCV catheterization. We will attest the beneficial effects of the ipsilateral tilt position on the csSCV and the primary venipuncture success rate during right SCV catheterization. Furthermore, comparisons of the first-pass success rate, complications, and total catheterization time during SCV catheterization in the ipsilateral tilt position vs. the supine position will help us determine which position is better for safe and easy SCV catheterization. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03296735 . Registered on 25 September 2017 for stage I; NCT03303274 Registered on 6 October 2017 for stage II. PMID- 29793549 TI - Meaning in life: resilience beyond reserve. AB - BACKGROUND: The contribution of psychological factors to brain health and resilience remains poorly investigated. Furthermore, their possible interaction with 'classical' cognitive reserve (CR) estimates in predicting perceived mental health and cognitive status has not been specifically addressed. METHODS: We obtained data from 1081 adults responding to questionnaires on the three meaning in life (MiL) dimensions: purpose in life (PiL), sense of coherence (SoC), and engagement with life (EwL). A questionnaire on CR variables was also administered. The outcome measures were self-reported cognitive function and affective status (depression, stress, and anxiety). Multiple linear regression analyses were used to evaluate the association between sociodemographic variables, MiL dimensions, and CR with the two selected outcomes. Mediation analyses, adjusted for age and gender, were applied to determine whether the MiL dimensions mediated the putative effects of CR on self-reported mental and cognitive health. RESULTS: All three MiL components, but not CR estimates, correlated with the self-reported affective status of the participants. Higher CR, PiL, and SoC (but not EwL) scores significantly correlated with higher perceived cognitive function. Notably, the observed association between the CR measures and self-reported cognitive function was mediated by PiL and SoC. CONCLUSIONS: Psychological MiL dimensions mediate the association between classic CR estimates and self-perceived cognitive function. Further studies on CR could consider including formal measures of such psychological factors to better understand their unique or synergistic contributions, as well as investigate the associated mechanisms maintaining brain function at older ages. PMID- 29793551 TI - Assessment of pattern and treatment outcome of patients admitted to pediatric intensive care unit, Ayder Referral Hospital, Tigray, Ethiopia, 2015. AB - OBJECTIVE: To describe admission pattern and outcome with its predictor variable on the mortality of children admitted to pediatric intensive care unit (PICU), Ayder Referral Hospital, Northern Ethiopia, from September 2012 to August 2014. RESULT: From 680 admitted patients, 400 patients were analyzed. Average age at admission was 62.99 +/- 60.94 months, with F:M ratio of 1:1.2. Overall (from infectious and non-infectious) the most commonly affected systems were respiratory (90/400 pts., 22.5%) and central nervous system (83/400 pts., 20.75%). Most were admitted due to meningitis (44/400 pts., 11%), post-operative (43/400 pts., 10.8%) and acute glomerulonephritis (41/400 pts., 10.3%). The overall mortality rate was 8.5%. Multivariable logistic regression shows, use of inotropes (p = 0.000), need for mechanical ventilator (p = 0.007) and presence of comorbid illness (p = 0.002), infectious cause (p = 0.015) and low level of Glasgow coma scale less than eight (p = 0.04) were independent predictors of mortality. From this study, common cause of PICU admission and death was meningitis. This highlights the importance of focusing on the preventable methods in the public such as vaccine, creating awareness about hygiene, and expanding ICU for early detection and for treatment acutely ill children. PMID- 29793553 TI - World Health Organization "School Mental Health Manual"-based training for school teachers in Urban Lahore, Pakistan: study protocol for a randomized controlled trial. AB - BACKGROUND: The teacher's role in school mental health initiatives cannot be overemphasized. Despite global evidence of educational interventions in improving teachers' knowledge and attitudes regarding mental health, this area remains under researched in Pakistan. This paper presents a study protocol of a pilot randomized controlled trial to examine the effectiveness of a teacher training intervention for improving mental health literacy and self-efficacy among school teachers in urban Lahore, Pakistan. METHODS: The randomized controlled trial will follow the CONSORT guidelines. Participants will be allocated to the Intervention group (receiving the World Health Organization, Eastern Mediterranean Region (WHO EMRO) School Mental Health Manual-based intervention in three 6-h, face-to-face sessions) or a waitlist control group (not receiving training during the study period). Participants will be teachers of private schools with similar broad demographic characteristics in an inner city area of Lahore. The primary outcome measures for the trial is teachers' mental health literacy. It will be assessed by using the previously applied (during WHO training of Master Trainers) self administered questionnaire in both groups pre and post training and at 3 months' follow-up. Secondary outcomes include: for teachers: Teachers' self-efficacy (assessed by the Teachers' Sense of Self Efficacy Scale (TSES) short form.); for students (11-16 years): socio-emotional skills and psychological problems measured by the Strengths and Difficulties Questionnaire (assessed at baseline and 3 months post intervention); for schools: the WHO School Psychosocial Profile Questionnaire (baseline and 3 months post intervention). DISCUSSION: Given the high prevalence of child mental health problems, stigma and lack of services, it is important to consider alternate avenues for promoting positive mental health among youth. This pilot study should establish the effectiveness of the WHO-EMRO School Mental Health Manual-based Intervention improving teacher's mental health literacy and helping them to learn practical steps that can be implemented at low cost in school settings. It will also provide information regarding intervention implementation and sustainability. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02937714 . Registered on 18 October 2016. PMID- 29793552 TI - A cut-off of daily sedentary time and all-cause mortality in adults: a meta regression analysis involving more than 1 million participants. AB - BACKGROUND: The appropriate limit to the amount of daily sedentary time (ST) required to minimize mortality is uncertain. This meta-analysis aimed to quantify the dose-response association between daily ST and all-cause mortality and to explore the cut-off point above which health is impaired in adults aged 18-64 years old. We also examined whether there are differences between studies using self-report ST and those with device-based ST. METHODS: Prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were identified via MEDLINE, PubMed, Scopus, Web of Science, and Google Scholar databases until January 2018. Dose-response relationships between daily ST and all-cause mortality were examined using random-effects meta-regression models. RESULTS: Based on the pooled data for more than 1 million participants from 19 studies, the results showed a log-linear dose-response association between daily ST and all-cause mortality. Overall, more time spent in sedentary behaviors is associated with increased mortality risks. However, the method of measuring ST moderated the association between daily ST and mortality risk (p < 0.05). The cut-off of daily ST in studies with self-report ST was 7 h/day in comparison with 9 h/day for those with device-based ST. CONCLUSIONS: Higher amounts of daily ST are log-linearly associated with increased risk of all-cause mortality in adults. On the basis of a limited number of studies using device based measures, the findings suggest that it may be appropriate to encourage adults to engage in less sedentary behaviors, with fewer than 9 h a day being relevant for all-cause mortality. PMID- 29793555 TI - Factors affecting use of ballistics gelatin in laboratory studies of bacterial contamination in projectile wounds. AB - BACKGROUND: Ballistics gelatin is a common tissue surrogate used in bacterial contamination models for projectile wounds. Although these studies have demonstrated that bacteria are transferred from the surface of the gelatin to the wound track by a projectile, quantifiable results have been inconsistent and not repeatable in successive tests. METHODS: In this study, five areas of a typical contamination model in which bacterial recovery or survival are affected were identified for optimization. The first was a contaminated "skin" surrogate, where the novel use of vacuum filtration of a bacterial culture and buffer onto filter paper was employed. The other possibly problematic areas of the bacterial distribution model included the determination of bacterial survival when the contamination model is dried, survival in solid and molten gelatin, and the effect of high-intensity lights used for recording high-speed video. RESULTS: Vacuum filtration of bacteria and buffer resulted in a consistent bacterial distribution and recovery. The use of phosphate buffer M9 (pH 7) aided in neutralizing the ballistics gelatin and improving bacterial survival in solid gelatin. Additionally, the use of high-intensity lights to record high-speed video and the use of a 42 degrees C water bath to melt the gelatin were found to be bactericidal for gram-positive and gram-negative bacteria. CONCLUSIONS: Multiple areas of a typical contamination model in which bacterial survival may be impeded were identified, and methods were proposed to improve survival in each area. These methods may be used to optimize the results of bacterial contamination models for medical applications, such as understanding the progression of infection in penetrating wounds and to identify possible sources of contamination for forensic purposes. PMID- 29793554 TI - Acute lung injury: how to stabilize a broken lung. AB - The pathophysiology of acute respiratory distress syndrome (ARDS) results in heterogeneous lung collapse, edema-flooded airways and unstable alveoli. These pathologic alterations in alveolar mechanics (i.e. dynamic change in alveolar size and shape with each breath) predispose the lung to secondary ventilator induced lung injury (VILI). It is our viewpoint that the acutely injured lung can be recruited and stabilized with a mechanical breath until it heals, much like casting a broken bone until it mends. If the lung can be "casted" with a mechanical breath, VILI could be prevented and ARDS incidence significantly reduced. PMID- 29793556 TI - Examination of the association of physical activity during pregnancy after cesarean delivery and vaginal birth among Chinese women. AB - BACKGROUND: The goal was to study whether higher physical activity can increase the success rate of Vaginal Birth after Cesarean Delivery (VBAC). METHODS: We enrolled 823 patients with previous cesarean section delivery history (between January 2015 and December 2017) and measured their physical activity during pregnancy. A final number of 519 patients were included for the trial of labor after cesarean delivery (TOLAC). All patients signed informed consent forms. RESULTS: We conducted bivariate analyses and identified that several variables were associated with successful VBAC: Prior history of vaginal birth (odds ratio [OR] 2.4, 95% CI 1.8-3.9); previous indication for primary cesarean delivery (OR 2.2, 95% CI 1.5-3.0); age younger than 40 years (OR 2.1, 95% CI 1.3-3.4); Weight gain less than 20 kg (OR 1.5, 95% CI 1.3-2.4); high pelvic/birth weight score (OR 1.4, 95% CI 1.1-2.0); no induction of labor (OR 1.9, 95% CI 1.4-2.8); and estimated prenatal fetal weight (OR 1.4, 95% CI 1.2-1.5). We also found that the bivariate association between physical activity and VBAC was significant (p = 0.002). In addition, there was higher odds of VBAC in women who had active physical activity of more than 150 min/week (adjusted OR 1.86, 95% CI 1.69-2.07). Lower odds of VBAC was associated with older age, weight gain during pregnancy, induction of labor, and having estimated prenatal fetal weight more than 3500 g. CONCLUSION: Physical activity during pregnancy may influence the success rate of VBAC in Chinese women. Future studies will be needed to prove the robustness of this association using more detailed exposure and outcome definitions. PMID- 29793558 TI - Efficacy of nature-based therapy for individuals with stress-related illnesses: randomised controlled trial. AB - BACKGROUND: Stress-related illnesses are a major threat to public health, and there is increasing demand for validated treatments.AimsTo test the efficacy of nature-based therapy (NBT) for patients with stress-related illnesses. METHOD: Randomised controlled trial (ClinicalTrials.gov ID NCT01849718) comparing Nacadia(r) NBT (NNBT) with the cognitive-behavioural therapy known as Specialised Treatment for Severe Bodily Distress Syndromes (STreSS). In total, 84 participants were randomly allocated to one of the two treatments. The primary outcome measure was the mean aggregate score on the Psychological General Well Being Index (PGWBI). RESULTS: Both treatments resulted in a significant increase in the PGWBI (primary outcome) and a decrease in burnout (the Shirom-Melamed Burnout Questionnaire, secondary outcome), which were both sustained 12 months later. No significant difference in efficacy was found between NNBT and STreSS for primary outcome and secondary outcomes. CONCLUSIONS: The study showed no statistical evidence of a difference between NNBT and STreSS for treating patients with stress-related illnesses.Declaration of interestNone. PMID- 29793557 TI - Human iPSC-MSCs prevent steroid-resistant neutrophilic airway inflammation via modulating Th17 phenotypes. AB - BACKGROUND: Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2) dominant eosinophilic allergic airway inflammation. However, the role of iPSC MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. METHODS: A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. RESULTS: We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORgammat were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. CONCLUSIONS: iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation. PMID- 29793559 TI - Bufalin induces apoptosis and improves the sensitivity of human glioma stem-like cells to temozolamide. AB - Glioma is the most common malignant tumor of the central nervous system and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, western blotting and reverse transcription-polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cells growth and proliferation, inhibits GSCs proliferation and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) and downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis and enhances the sensitivity of GSCs to TMZ. PMID- 29793562 TI - Social Media and Its Implications in Pediatric Dentistry. AB - Social media is increasingly being relied upon by health care professionals, including pediatric dentists, to make decisions in their practices. While social media serves as an excellent resource, there is lack of sound guidelines on its use by health professionals in dentistry. Pediatric dentists using social media for professional purposes need to be aware of the uses as well as the challenges it presents. More importantly, members and moderators of social media groups should ensure that all patient care-related information is de-identified and discussions are compliant with federal and state privacy laws and based on evidence-based recommendations. PMID- 29793563 TI - Effectiveness of Acupressure on Dental Anxiety in Children. AB - PURPOSE: Acupressure is a non-invasive variant of acupuncture and is known to reduce general anxiety. The purpose of this study was to test acupressure's effect on children's dental anxiety. METHODS: Eight- to 12-year-old children undergoing scaling and/or restorative procedures were randomly assigned to one of the following groups: acupressure (Group 1); sham (Group 2); or control (Group 3). Anxiety was recorded for all the children using the Modified Child Dental Anxiety scale (MCDAS). Acupressure beads with a piece of adhesive strip were employed over the selected acupoints for groups one and two. Anxiety was further recorded for all the children prior to and after completion of the treatment using MCDAS. The Frankl scale was used as the objective measure to assess the behavior of all the children. A physiologic parameter (pulse rate) was also recorded. The scores obtained from all the three groups were tabulated, compared, and analyzed statistically. RESULTS: A significant difference was found in MCDAS, pulse rate, and the Frankl behavior ratings among the three groups of children, with acupressure group displaying a lower level of anxiety. CONCLUSION: Acupressure can be a viable alternative to reduce dental anxiety in children undergoing scaling and restorative procedures. PMID- 29793564 TI - Mineral Trioxide Aggregate Partial Pulpotomy Versus Formocresol Pulpotomy: A Randomized, Split-Mouth, Controlled Clinical Trial with 24 Months Follow-Up. AB - PURPOSE: The purpose of this study was to evaluate the clinical and radiographic success rates of mineral trioxide aggregate partial pulpotomy (PP) compared to formocresol pulpotomy (FP) in human primary molars. METHODS: In this randomized, controlled, split-mouth, clinical trial, 25 healthy five- to eight-year-olds, with 50 carious primary mandibular second molars lacking clinical and radiographic evidence of pulp pathology, were selected. The selected teeth were randomly assigned into two groups, PP and FP, for vital pulp therapy. Stainless steel crowns were placed as final restorations for both groups. Clinical and radiographic evaluation at six, 12, and 24 months used the following criteria for failure: pain; swelling; sinus tract; mobility; internal or external root resorption; furcation or periapical radiolucency; and widening of periodontal ligament space. The data were analyzed using a binary logistic generalized estimating equation model. RESULTS: At the 12-month and 24-month follow-ups, one child and three children, respectively, were lost to follow-up. At the 24-month follow-up, the clinical, radiographic, and overall success rates of PP were 90.9 percent, 90.5 percent, and 81.8 percent versus FP success of 100 percent, 95.2 percent, and 95.2 percent, respectively. CONCLUSION: There were no significant differences between clinical, radiographic, and overall success rate of mineral trioxide aggregate partial pulpotomy and formocresol pulpotomy overall 24 months. PMID- 29793565 TI - A Randomized Clinical Trial Evaluating Rubber Dam Clamp Pain Reduction from a New Topical Liposomal Anesthetic Gel. AB - PURPOSE: Discomfort during rubber dam clamp often occurs in pediatric dentistry. The purpose of this randomized, triple-blind, clinical trial was to evaluate the effect of pain reduction using a new topical liposomal thermo-sensitive gel (TLTG) or a placebo gel during rubber dam clamp isolation for sealants in children. METHODS: Eighty-one children (eight to 12 years old) had LTSG or the placebo gel with random assignment placed around the gingival tissue of their permanent mandibular first molars. A clamp was placed after two minutes on the teeth, and intensity of pain was registered using a Wong-Baker FACES scale and an 11-point numerical scale. The data were evaluated using McNemar's test and Wilcoxon signed rank test. RESULTS: The odds ratio for pain (OR equals 0.7; 95 percent confidence interval equals 0.3 to 1.8) was not statistically significant (P=0.52). However, there was a small difference in the pain intensity between liposomal and placebo groups for both scales (P<0.05). CONCLUSION: The liposomal thermo-sensitive anesthetic gel may reduce, to a small extent, the pain intensity in children submitted to rubber dam isolation before resin sealant placement. PMID- 29793566 TI - Radiographic Effectiveness of Resin Infiltration in Arresting Incipient Proximal Enamel Lesions in Primary Molars. AB - PURPOSE: The purpose of this split-mouth, randomized, prospective clinical trial was to evaluate radiographically the effectiveness of resin infiltration, as an adjunct to standard-of-care preventive measures compared to standard-of-care preventive measures alone, in arresting the progression of non-adjacent, incipient, proximal enamel lesions in primary molars 24 months after treatment. METHODS: The study included a total of 45 healthy five- to eight-year-olds who had been diagnosed radiographically with at least two non-adjacent, incipient, proximal enamel lesions in primary molars (90 lesions). Test group lesions were treated using resin infiltration followed by five percent topical sodium fluoride (NaF) application versus five percent NaF alone in the control group. The alpha level was set at 0.05. RESULTS: The children were examined after six, 12, 18, and 24 months. Twenty-five subjects were examined at the 24-month follow-up visit, At which time 10 of the 25 test lesions (40 percent) showed caries progression while 18 of the 25 control lesions (72 percent) showed caries progression (P=0.04). CONCLUSION: Resin infiltration as an adjunct to standard-of-care preventive measures is significantly more effective radiographically in reducing the progression of non-adjacent, incipient, proximal enamel lesions in primary molars compared with standard-of-care preventive measures alone after 24 months. PMID- 29793567 TI - Usage of Behavior Guidance Techniques Differs by Provider and Practice Characteristics. AB - PURPOSE: The purpose of this study was to determine provider and practice characteristics influencing usage of behavior guidance techniques (BGTs). METHODS: A 24-item survey was emailed to 4,117 active AAPD members to identify factors influencing pediatric dentists' use of BGTs. RESULTS: A total of 1,081 surveys were returned, for a 26 percent response rate. The mean age of respondents was 44.7 years old, with recent graduates comprising the largest group (30.5 percent). Usage of voice control, nitrous oxide, sedation, and general anesthesia (GA) differed significantly, according to experience. Respondents with at least 30 years of experience reported changes in usage. Tell show-do, nitrous oxide, oral sedation, and passive restraint were significantly more frequent among female respondents. Parental absence, oral sedation, and GA were significantly more frequent in respondents serving low income populations. Parental absence, pharmacologic techniques, and restraint were significantly different in frequencies among the different geographic regions. CONCLUSIONS: Usage of behavior guidance techniques has changed over the past three decades, with more recent graduates and experienced practitioners now emphasizing pharmacologic techniques. More assertive behavior guidance techniques are used more frequently by experienced providers and those in practices in the southwest or serving lower income populations. Pharmacologic techniques are used at a higher prevalence by recent graduates and providers who are female or serving lower income populations. PMID- 29793569 TI - Oral Health of Patients with Special Health Care Needs After General Anesthesia: A 25- Year Retrospective Study. AB - PURPOSE: The purpose of this study was to compare the oral health state and dental treatment outcomes of patients with special health care needs (SHCN) after general anesthesia (GA), according to their compliance with dental checkups. METHODS: The medical records of SHCN patients who were treated under GA in a dental hospital from 1991 to 2016 were analyzed. The 157 patients in this study were divided into regular (N equals 62) and irregular (n equals 95) dental checkups. RESULTS: The mean age was 16.4 years (range equals two to 52); 96 were male, and 61 were female. In the irregular checkup group, invasive treatments like pulp treatment and extraction were performed more frequently during the checkup period (P<0.05). More patients underwent repeated GA in the irregular group (n equals 35; 36.8 percent) compared to the regular group (n equals six; 9.7 percent; P<0.05). CONCLUSIONS: In our study, special health care needs patients in the irregular checkup group were approximately four times more likely to undergo repeated general anesthesia than those in the regular group. A regular checkup could reduce repeated GA and severity of dental treatment. Therefore, regular checkups must be included in the treatment plan of SHCN patients. PMID- 29793568 TI - Survival and Associated Risk Factors of Composite Restorations in Children with Early Childhood Caries: A Clinical Retrospective Study. AB - PURPOSE: The purpose of this clinical retrospective study was to assess survival and risk factors associated with failures of resin composite restorations placed in patients with early childhood caries. METHODS: Seventy-eight restorations in primary teeth from records of 24 high caries risk children were included in the study. The restorations' longevity up to 30 months of follow-up was assessed using the Kaplan-Meier survival test. Multivariate Cox regression analysis with shared frailty was used to evaluate the factors associated with failures (P<0.05). RESULTS: Mean survival time was 26 months (95 percent confidence interval = 24.5 to 26.7). The survival of the restorations reached 34.8 percent up to 30 months, with an overall annual failure rate of 20 percent. Restorations involving two or more surfaces had 2.50 times more risk of failure than restorations involving single surface (P=0.03). Restorations performed in vital teeth had a lower risk of failure than those performed in teeth that underwent pulp intervention (hazard ratio equals 0.25; 95 percent confidence interval =0.10 to 0.65; P=0.00). Patients with a plaque index more than 20 percent had 3.63 times more risk of failure in their restorations (P=0.01). CONCLUSION: Clinical variables, such as the number of restored surfaces, pulp therapy, and poor biofilm control, may affect the survival of composite restorations performed in patients with early childhood caries. PMID- 29793571 TI - Effect of Repeated Sterilization on the Tensile Strength of Rubber Dam Clamps. AB - PURPOSE: The fracture of rubber dam clamps after repeated clinical uses can result in ingestion/aspiration of the fragments. This pilot study was aimed at examining whether the tensile strength of a rubber dam clamp changes significantly following the stresses of repeated clinical use and steam sterilizations. METHODS: One-hundred new stainless-steel rubber dam clamps were subjected to repeated steam sterilization and placement on a wooden dowel periodically, simulating clinical use. Two clamps were randomly selected for removal after every 50 sterilization cycles. Three-hundred such cycles were completed. Using a standard bench top universal tensile testing system (MTI-2K) a tensile force was applied to break the new clamps and the clamps that were stretched and autoclaved. The maximum force was recorded, and data analyzed using simple mean. The mean tensile load values were plotted on a graph against the number of sterilization cycles to analyze trends in the data. RESULTS: The rubber dam clamps demonstrated a higher tensile strength and fracture resistance after three-hundred cycles of use and sterilization. CONCLUSION: Repeated use and steam sterilization up to three-hundred cycles did not adversely affect the tensile strength of the rubber dam clamps. The clamps, in fact, demonstrated a higher tensile strength. PMID- 29793572 TI - Electronic fetal monitoring or cardiotocography, 50 years later: what's in a name? PMID- 29793573 TI - Pain relief: determining the safety of ibuprofen with postpartum preeclampsia. PMID- 29793574 TI - Retraction notice to Granisetron, droperidol, and metoclopramide for the treatment of established postoperative nausea and vomiting in women undergoing gynecologic surgery: Am J Obstet Gynecol 2000;182:13-16. AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief. In 2012, a number of Editors-in-Chief requested a determination from several universities regarding the body of work published by Dr. Yoshitaka Fujii. An investigation by the University of Tsukaba, Japan, where the above work was conducted, concluded that Dr. Fujii made a false statement that the research had been approved by the Institutional Review Board and a false statement that he conducted the randomized clinical trial by himself. This retraction in AJOG was delayed due to an editorial oversight. PMID- 29793575 TI - Corrigendum. PMID- 29793576 TI - Epidemic Keratoconjunctivitis: (Superficial Punctate Keratitis, Keratitis Subepithelialis, Keratitis Maculosa, Keratitis Nummularis) With a Review of the Literature and a Report of 125 Cases. PMID- 29793577 TI - Shades of grey: embracing uncertainty in the exercise room. PMID- 29793578 TI - Pain and pain prescribing: what is in a number? PMID- 29793579 TI - Optimising conditions for tracheal intubation: should neuromuscular blocking agents always be used? PMID- 29793580 TI - Best arrive on time. PMID- 29793581 TI - A small step in the right direction for reducing postoperative pulmonary complications. PMID- 29793582 TI - Cardiac troponin I as an early prognosis biomarker after trauma: a retrospective cohort study. AB - BACKGROUND: The significance of cardiac troponin I (cTnI) elevation after trauma is debated. We therefore explored the association between cTnI elevation at admission after trauma and ICU mortality. METHODS: We performed a retrospective analysis from a prospectively constituted database, of patients admitted to ICU after trauma at a single centre, over a 36 month period. According to cTnI plasma concentration at admission, patients were categorised into three groups: normal (<0.05 ng ml-1), intermediate (0.05-0.99 ng ml-1), or high concentration (>=1.0 ng ml-1). Associations of pre-hospital conditions or cTnI elevation and mortality were analysed by multivariate logistic regression. RESULTS: Among the 994 patients, 177 (18%) had cTnI elevation at ICU admission. Of this total, 114 (11%) patients died in the ICU. The cTnI release was an independent predictor of ICU mortality with a concentration-response relationship [odds ratio (OR) 4.90 (2.19 11.16) and 14.83 (4.68-49.90) for intermediate and high concentrations, respectively] and Day 2 mortality [OR 2.23 (1.18-5.80) and 7.49 (2.77-20.12) for intermediate and high concentrations, respectively]. The severity of thoracic trauma [OR 2.25 (1.07-4.55) and 3.23 (2.00-5.27) for Abbreviated Injury Scale scores 1-2 and >=3, respectively], out-of-hospital maximal heart rate >=120 beats min-1 [OR 2.22 (1.32-3.69)], and out-of-hospital shock [OR 2.02 (1.20-3.38)] were independently associated with cTnI elevation. CONCLUSIONS: Release of cTnI was an independent predictor of ICU mortality, suggesting that this biomarker can be used in daily practice for early stratification of the risk of ICU death. Thoracic trauma was strongly associated with cTnI elevation. PMID- 29793584 TI - Effect of intraoperative hyperoxia on the incidence of surgical site infections: a meta-analysis. AB - BACKGROUND: Whether supplemental intraoperative oxygen reduces surgical site infections remains unclear. Recent recommendations from the World Health Organization and Center for Disease Control to routinely use high inspired oxygen concentrations to reduce infection risk have been widely criticized. We therefore performed a meta-analysis to evaluate the influence of inspired oxygen on infection risk, including a recent large trial. METHODS: A systematic literature search was performed. Primary analysis included all eligible trials. Sensitivity analyses distinguished studies of colorectal and non-colorectal surgeries, and excluded studies with high risk of bias. Another post-hoc sensitivity analysis excluded studies from one author that appear questionable. RESULTS: The primary analysis included 26 trials (N=14,710). The RR [95%CI] for wound infection was 0.81 [0.70, 0.94] in the high vs. low inspired oxygen groups. The effect remained significant in colorectal patients (N=10,469), 0.79 [0.66, 0.96], but not in other patients (N=4,241), 0.86 [0.69, 1.09]. When restricting the analysis to studies with low risk of bias, either by strict inclusion criteria (N=5,047) or by researchers' judgment (N=12,547), no significant benefit remained: 0.84 [0.67, 1.06] and 0.89 [0.76, 1.05], respectively. CONCLUSIONS: When considering all available data, intraoperative hyperoxia reduced wound infection incidence. However, no significant benefit remained when analysis was restricted to objective- or investigator-identified low-bias studies, although those analyses were not as well-powered. Meta-analysis of the most reliable studies does not suggest that supplemental oxygen substantively reduces wound infection risk, but more research is needed to fully answer this question. PMID- 29793583 TI - Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass. AB - BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers. PMID- 29793585 TI - The cardiopulmonary exercise test grey zone; optimising fitness stratification by application of critical difference. AB - BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification. METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (VO2-AT): 11 ml O2 kg-1 min-1, peak oxygen uptake (VO2 peak): 16 ml O2 kg-1 min 1, and ventilatory equivalent for carbon dioxide at AT (VE/VCO2-AT): 36]. RESULTS: The critical difference for VO2-AT, VO2 peak, and VE/VCO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and >=13.6 ml O2 kg-1 min-1, VO2 peak <14.2 and >=18.3 ml kg-1 min-1, VE/VCO2-AT >=40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness. CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for. PMID- 29793586 TI - Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis. AB - BACKGROUND: Perioperative anaphylaxis (POA) is infrequent, but remains an important and potentially life-threatening complication of general anaesthesia. The diagnostic uncertainty surrounding the investigation of anaesthetic allergy poses numerous challenges. We aimed to inform practice by auditing the outcomes of repeat anaesthesia, after an investigation for previous POA. METHODS: One hundred and seventy-four subjects were investigated after suspected POA between December 2002 and August 2015. Outcome data were obtained for a total of 70 patients who underwent repeat anaesthesia after investigation in the drug-allergy clinic. RESULTS: Sixty-seven out of the 70 patients studied underwent repeat anaesthesia without further complications. Three individuals experienced a further episode of anaphylaxis. In two cases, incomplete referral information led to the offending drugs being omitted from initial testing. The third was found to have underlying systemic mastocytosis (SM). CONCLUSIONS: In our cohort, the incidence of repeat anaphylaxis after a comprehensive assessment in the drug allergy clinic for suspected POA was 4%. Important risk factors include the completeness of referral information provided to the assessor and the role of exacerbating disorders, particularly SM. PMID- 29793587 TI - Cefazolin tissue concentrations with a prophylactic dose administered before sleeve gastrectomy in obese patients: a single centre study in 116 patients. AB - BACKGROUND: In obese patients undergoing sleeve gastrectomy, the blood and fatty tissue concentrations of cefazolin required for adequate antibiotic prophylaxis are uncertain. METHODS: This was a single centre prospective study in obese (Group A: 40<= BMI <=50 kg m-2) and severely obese (Group B: 50< BMI <=65 kg m-2) patients undergoing bariatric surgery. Blood and fatty-tissue samples were collected after a cefazolin 4 g i.v. injection. The primary aim was to compare cefazolin concentrations in subcutaneous fatty tissue with a targeted tissue concentration of 4 MUg g-1 according to Staphylococcus aureus resistance breakpoint. RESULTS: One hundred and sixteen patients were included: 79 in Group A and 37 in Group B. At the beginning of the surgery, cefazolin concentration in subcutaneous fatty tissue was 12.2 (5.4) MUg g-1 in Group A and 12 (6.1) MUg g-1 in Group B (P=0.7). At the end, cefazolin concentrations in subcutaneous fatty tissue were 9.0 (4.9) and 7.8 (4.2) MUg g-1 in Groups A and B, respectively (P=0.2). The plasma concentration of free cefazolin during surgery was higher in Group A than in Group B (P<0.0001). Fatty-tissue concentrations of 95% and 83% patients in Groups A and B, respectively, were above S. aureus resistance breakpoint. CONCLUSIONS: After a 4 g dose, the concentrations of cefazolin in fatty tissue were above the 4 MUg g-1 tissue concentration target, providing adequate antibiotic tissue concentrations during bariatric surgery. As cefazolin concentration in fatty tissue is a surrogate endpoint, the results should be considered in conjunction with the results on free cefazolin concentrations in subcutaneous tissue. CLINICAL TRIAL REGISTRATION: NCT01537380. PMID- 29793588 TI - Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation. AB - BACKGROUND: The non-linear mixed amount with zero amounts response surface model can be used to describe drug interactions and predict loss of response to noxious stimuli and respiratory depression. We aimed to determine whether this response surface model could be used to model sedation with the triple drug combination of midazolam, alfentanil and propofol. METHODS: Sedation was monitored in 56 patients undergoing gastrointestinal endoscopy (modelling group) using modified alertness/sedation scores. A total of 227 combinations of effect-site concentrations were derived from pharmacokinetic models. Accuracy and the area under the receiver operating characteristic curve were calculated. Accuracy was defined as an absolute difference <0.5 between the binary patient responses and the predicted probability of loss of responsiveness. Validation was performed with a separate group (validation group) of 47 patients. RESULTS: Effect-site concentration ranged from 0 to 108 ng ml-1 for midazolam, 0-156 ng ml-1 for alfentanil, and 0-2.6 MUg ml-1 for propofol in both groups. Synergy was strongest with midazolam and alfentanil (24.3% decrease in U50, concentration for half maximal drug effect). Adding propofol, a third drug, offered little additional synergy (25.8% decrease in U50). Two patients (3%) experienced respiratory depression. Model accuracy was 83% and 76%, area under the curve was 0.87 and 0.80 for the modelling and validation group, respectively. CONCLUSION: The non linear mixed amount with zero amounts triple interaction response surface model predicts patient sedation responses during endoscopy with combinations of midazolam, alfentanil, or propofol that fall within clinical use. Our model also suggests a safety margin of alfentanil fraction <0.12 that avoids respiratory depression after loss of responsiveness. PMID- 29793589 TI - Characteristic pattern of pleural effusion in electrical impedance tomography images of critically ill patients. AB - BACKGROUND: Electrical impedance tomography (EIT) is increasingly used for continuous monitoring of ventilation in intensive care patients. Clinical observations in patients with pleural effusion show an increase in out-of-phase impedance changes. We hypothesised that out-of-phase impedance changes are a typical EIT finding in patients with pleural effusion and could be useful in its detection. METHODS: We conducted a prospective observational study in intensive care unit patients with and without pleural effusion. In patients with pleural effusion, EIT data were recorded before, during, and after unilateral drainage of pleural effusion. In patients with no pleural effusion, EIT data were recorded without any intervention. EIT images were separated into four quadrants of equal size. We analysed the sum of out-of-phase impedance changes in the affected quadrant in patients with pleural effusion before, during, and after drainage and compared it with the sum of out-of-phase impedance changes in the dorsal quadrants of patients without pleural effusion. RESULTS: We included 20 patients with pleural effusion and 10 patients without pleural effusion. The median sum of out-of-phase impedance changes was 70 (interquartile range 49-119) arbitrary units (a.u.) in patients with pleural effusion before drainage, 25 (12-46) a.u. after drainage (P<0.0001) and 11 (6-17) a.u. in patients without pleural effusion (P<0.0001 vs pleural effusion before drainage). The area under the receiver operating characteristics curve was 0.96 (95% limits of agreement 0.91-1.01) between patients with pleural effusion before drainage and those without pleural effusion. CONCLUSIONS: In patients monitored with EIT, the presence of out-of phase impedance changes is highly suspicious of pleural effusion and should trigger further examination. PMID- 29793590 TI - Prospective study of device-related complications in intensive care unit detected by virtual autopsy. AB - BACKGROUND: There has been increasing use of invasive techniques, such as extracorporeal organ support, in intensive care units (ICU), and declining autopsy rates. Thus, new measures are needed to maintain high-quality standards. We investigated the potential of computed tomography (CT)-based virtual autopsy to substitute for medical autopsy in this setting. METHODS: We investigated the potential of virtual autopsy by post-mortem CT to identify complications associated with medical devices in a prospective study of patients who had died in the ICU. Clinical records were reviewed to determine the number and types of medical devices used, and findings from medical and virtual autopsies, related and unrelated to the medical devices, were compared. RESULTS: Medical and virtual autopsies could be performed in 61 patients (Group M/V), and virtual autopsy only in 101 patients (Group V). In Group M/V, 41 device-related complications and 30 device malpositions were identified, but only with a low inter-method agreement. Major findings unrelated to a device were identified in about 25% of patients with a high level of agreement between methods. In Group V, 8 device complications and 36 device malpositions were identified. CONCLUSIONS: Device related complications are frequent in ICU patients. Virtual and medical autopsies showed clear differences in the detection of complications and device malpositions. Both methods should supplement each other rather than one alone for quality control of medical devices in the ICU. Further studies should focus on the identification of special patient populations in which virtual autopsy might be of particular benefit. CLINICAL TRIAL REGISTRATION: NCT01541982. PMID- 29793592 TI - Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock. AB - BACKGROUND: During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. METHODS: Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. RESULTS: Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. CONCLUSIONS: Resuscitation from haemorrhagic shock using terlipressin with small volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions. PMID- 29793591 TI - Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. AB - BACKGROUND: The role of vasopressors in trauma-related haemorrhagic shock (HS) remains a matter of debate. They are part of the most recent European recommendations on the management of HS and are regularly used in France. We assessed the effect of early administration of noradrenaline in 24 h mortality of trauma patients in HS, using a propensity-score analysis. METHODS: The study included patients from a multicentre prospective regional trauma registry. HS was defined as transfusion of >=4 erythrocyte-concentrate units during the first 6 h. Patients with a Glasgow coma scale=3 and pre-hospital traumatic cardiac arrest were excluded. The main outcome measure was in-hospital mortality. The explicative and adjustment variables for the outcome and treatment allocation were predetermined by a Delphi method. The in-hospital mortality of patients with and without early administration of noradrenaline was compared in a propensity score model, including all predetermined variables. RESULTS: Of 7141 patients in the registry in the study period, 6353 were screened and 518 patients in HS (201 with early noradrenaline use and 317 without) were included and analysed. After propensity-score matching, 100 patients remained in each group, and the hazard ratio mortality was 0.95 (95% confidence interval: 0.45-2.01; P=0.69). CONCLUSIONS: The results of the present study suggest that noradrenaline use in the early phase of traumatic HS does not seem to affect mortality adversely. This observation supports a rationale for equipoise in favour of a prospective trial of the use of vasopressors in HS after trauma. PMID- 29793593 TI - Systematic review of the neurocognitive outcomes used in studies of paediatric anaesthesia neurotoxicity. AB - BACKGROUND: Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. METHODS: We conducted a systematic review to identify all measures used to assess long-term neurocognitive outcomes following general anaesthesia (GA) and surgery in children. The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS) for observational studies. PubMed/MEDLINE, EMBASE, Cinahl, Web of Science, and the Cochrane Library were searched for studies investigating neurocognitive outcome after GA in children <18 yr. RESULTS: Sixty-seven studies were identified from 19 countries during 1990-2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other outcomes (magnetic resonance imaging, serum-biomarkers, mortality, neurological examination, measurement of head circumference, impairment of vision). Rating according to the NOS rewarded a mean of six stars out of nine. Some concerns prevail regarding potential inter-rater variability because of equivocal description of rating criteria. Specific features such as stability over lifetime and inter-relations of outcomes (e.g. prediction of subsequent development or diagnosis of neuropsychological conditions) are discussed. The importance of validity and reliability of the various test instruments are described. The studies vary immensely in important characteristics. CONCLUSIONS: Future observational studies should be more consistent in the choice of study population, age at exposure, follow-up, indication for and type of surgery, and outcomes. Assessment of sensory-motor development seems feasible in young children (age <4 yr), and intelligence/cognition in older children. PMID- 29793594 TI - Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old. AB - BACKGROUND: General anaesthetics generate spatially defined brain oscillations in the EEG that relate fundamentally to neural-circuit architecture. Few studies detailing the neural-circuit activity of general anaesthesia in children have been described. The study aim was to identify age-related changes in EEG characteristics that mirror different stages of early human brain development during sevoflurane anaesthesia. METHODS: Multichannel EEG recordings were performed in 91 children aged 0-3 yr undergoing elective surgery. We mapped spatial power and coherence over the frontal, parietal, temporal, and occipital cortices during maintenance anaesthesia. RESULTS: During sevoflurane exposure: (i) slow-delta (0.1-4 Hz) oscillations were present in all ages, (ii) theta (4-8 Hz) and alpha (8-12 Hz) oscillations emerge by ~4 months, (iii) alpha oscillations increased in power from 4 to 10 months, (iv) frontal alpha oscillation predominance emerged at ~6 months, (v) frontal slow oscillations were coherent from birth until 6 months, and (vi) frontal alpha oscillations became coherent ~10 months and persisted in older ages. CONCLUSIONS: Key developmental milestones in the maturation of the thalamo-cortical circuitry likely generate changes in EEG patterns in infants undergoing sevoflurane general anaesthesia. Characterisation of anaesthesia-induced EEG oscillations in children demonstrates the importance of developing age-dependent strategies to monitor properly the brain states of children receiving general anaesthesia. These data have the potential to guide future studies investigating neurodevelopmental pathologies involving altered excitatory-inhibitory balance, such as epilepsy or Rett syndrome. PMID- 29793596 TI - Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury. AB - BACKGROUND: The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). METHODS: Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). RESULTS: Compared with the TBI saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. CONCLUSIONS: These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. PMID- 29793595 TI - The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke. AB - BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237. PMID- 29793597 TI - Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials. AB - BACKGROUND: Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. METHODS: We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. RESULTS: Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (<=3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (<=20%) 21%, 95% CI 13-29%]. CONCLUSIONS: Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42016047335. PMID- 29793598 TI - Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. AB - The focus of perioperative pain management should be to attempt to minimise the nociceptive input and reduce the risk of transition to central sensitisation. Gabapentinoids are being increasingly used as adjuncts for management of perioperative pain. Although gabapentinoids are classed as calcium channel blockers, their mechanisms of action are poorly understood. The analgesic effect in neuropathic pain is well evidenced but the role in postoperative pain is less certain. Medline and EMBASE database searches were conducted to identify studies relating to mechanisms of action and effects in experimental animal models of inflammatory and postoperative pain and human models of experimental pain. The effects of gabapentinoids may be attributed to depression of dorsal horn sensitivity through a multitude of mechanisms. They inhibit calcium mediated neurotransmitter release through effects on alpha2delta-1 subunits. They inhibit forward trafficking of alpha2delta-1 from the dorsal root ganglion, their recycling from endosomal compartments, thrombospondin mediated processes and stimulate glutamate uptake by excitatory amino acid transporters. Mechanisms not directly related to neurotransmitter release at dorsal horn include inhibition of descending serotonergic facilitation, stimulation of descending inhibition, anti inflammatory actions, and influence on the affective component of pain. Gabapentinoids are effective analgesics in most animal models of inflammation and postoperative pain but effects in human models are variable. PMID- 29793599 TI - Incidence of iatrogenic opioid dependence or abuse in patients with pain who were exposed to opioid analgesic therapy: a systematic review and meta-analysis. AB - BACKGROUND: The prevalence and incidence of chronic conditions, such as pain and opioid dependence, have implications for policy development, resource allocation, and healthcare delivery. The primary objective of the current review was to estimate the incidence of iatrogenic opioid dependence or abuse after treatment with opioid analgesics. METHODS: Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, Cinahl Plus, Web of Science, OpenGrey). A 'grey' literature search and a reference search of included articles were also undertaken. The PICOS framework was used to develop search strategies and the findings are reported in accordance with the PRISMA Statement. RESULTS: After eligibility reviews of 6164 articles, 12 studies (involving 310 408 participants) were retained for inclusion in the meta-analyses. A random effects model (DerSimonian-Laird method) generated a pooled incidence of opioid dependence or abuse of 4.7%. There was little within-study risk of bias and no significant publication bias; however, substantial heterogeneity was found among study effects (99.78%). Sensitivity analyses indicated that the diagnostic criteria selected for identifying opioid dependence or abuse (Diagnostic Statistical Manual (DSM-IV) vs International Classification of Diseases (ICD-9)) accounted for 20% and duration of exposure to opioid analgesics accounted for 18% of variance in study effects. Longer-term opioid analgesic exposure, and prescription of strong rather than weak opioids, were associated with a significantly lower incidence of opioid dependence or abuse. CONCLUSIONS: The incidence of iatrogenic opioid dependence or abuse was 4.7% of those prescribed opioids for pain. Further research is required to confirm the potential for our findings to inform prevention of this serious adverse event. PMID- 29793600 TI - Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study. AB - BACKGROUND: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. METHODS: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003-2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. chi2 tests examined associations between individual pain severity and opioid prescriptions. RESULTS: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25-40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. CONCLUSIONS: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common. PMID- 29793601 TI - Adiponectin regulates thermal nociception in a mouse model of neuropathic pain. AB - BACKGROUND: Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. METHODS: Wild type (WT) and adiponectin KO mice were subjected to partial sciatic nerve ligation (pSNL) or sham operation. Pain-like behavioural tests, including thermal allodynia, hyperalgesia, and mechanical allodynia, were performed before and after pSNL from Day 3-21. Dorsal root ganglions (DRGs), lumbar spinal segments at L3-5, and somatosensory cortex were collected for protein measurement via western blotting and immunofluorescence staining. RESULTS: Compared with WT mice, KO mice had significantly lower (40-50%) paw withdrawal latency to innocuous and noxious stimuli before and after pSNL. In DRG neurones from KO mice, where adiponectin receptor (AdipoR) 2 is located, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and heat-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) were significantly higher (by two- to three fold) than from WT mice. In spinal microglia and somatosensory cortical neurones, where AdipoR1 is mainly located, p-p38 MAPK and TRPV1 were also higher (by two- to three-fold) in KO compared with WT mice, and altered signalling of these molecules was exacerbated (1.2- to 1.3-fold) by pSNL. CONCLUSIONS: Our results show that adiponectin regulates thermal nociceptive sensitivity by inhibiting activation of DRG neurones, spinal microglia, and somatosensory cortical neurones in physiological and neuropathic pain states. This study has relevance for patients with adiponectin disorders, such as obesity and diabetes. PMID- 29793602 TI - Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation. AB - BACKGROUND: Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. METHODS: Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. RESULTS: The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. CONCLUSIONS: Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients. PMID- 29793603 TI - Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review. AB - Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19 21.49, P<0.00001, TSA-adjusted CI 1.85-95.04]. The result was confirmed when including all trials, (RR 5.00, 95% CI 3.49-7.15, P<0.00001, TSA-adjusted CI 1.20 20.77). There was a significant risk of upper airway discomfort or injury by avoiding NMBA (RR=1.37, 95% CI 1.09-1.74, P=0.008, TSA-adjusted CI 1.00-1.86). None of the trials reported mortality. Avoiding NMBA was significantly associated with difficult laryngoscopy, (RR 2.54, 95% CI 1.53-4.21, P=0.0003, TSA-adjusted CI 0.27-21.75). In a clinical context, one must balance arguments for using NMBA when performing tracheal intubation. PMID- 29793604 TI - Influence of xenon on pulmonary mechanics and lung aeration in patients with healthy lungs. AB - BACKGROUND: The anaesthetic xenon shows potent organ-protective properties. Due to high density and dynamic viscosity, peak inspiratory pressure (Pmax) increases during xenon application. Thus, barotrauma may counteract organ protection. Accordingly, we investigated the influence of xenon on lung mechanics and lung aeration in patients with normal and reduced thoracic wall compliance. METHODS: After registration and ethical approval, 20 patients free of pulmonary disease undergoing routine xenon-based anaesthesia were mechanically ventilated. The primary outcome variable transpulmonary pressure (Ptp) was determined from plateau pressure and intraoesophageal pressure before and after xenon wash-in. We recorded Pmax, and calculated airway resistance (RAW), and static (Cstat) and dynamic (Cdyn) respiratory compliances. Finally, lung aeration was quantified by electrical impedance tomography-derived centre of ventilation index (CVI) and global inhomogeneity index (GI) in the awake state, before and during xenon. RESULTS: Xenon increased Pmax [20.8 (SD 3) vs 22.6 (3) cm H2O, P<0.001] and RAW [0.9 (0.2) vs 1.4 (0.3) cm H2O litre-1 s, P<0.001], without affecting Ptp [1.5 (4) vs 2.0 (4) cm H2O, P=0.15]. While Cstat remained unchanged, Cdyn was reduced [33.9 (7) vs 31.2 (6) ml (cm H2O)-1, P<0.001). A ventral tidal volume shift after anaesthesia induction [CVI 0.53 (0.03) vs 0.59 (0.04), P<0.001] was unaltered during xenon [CVI 0.59 (0.04), P=0.29]. Homogeneity of lung aeration was also unchanged during xenon [GI 0.37 (0.03) vs 0.37 (0.03), P=0.99]. There were no clinically meaningful differential BMI-related effects. CONCLUSIONS: Xenon increases calculated airway resistance and peak inspiratory pressure without affecting transpulmonary pressure, independent of BMI. CLINICAL TRIAL REGISTRATION: NCT02682758. PMID- 29793605 TI - Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects. AB - BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. METHODS: Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 MUg kg-1 min-1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. RESULTS: No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. CONCLUSIONS: Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. CLINICAL TRIAL REGISTRATION: NTR4735. PMID- 29793607 TI - Adverse outcomes after planned surgery with anticipated intensive care admission in out-of-office-hours time periods: a multicentre cohort study. AB - BACKGROUND: Increasing mortality for patients admitted to hospitals during the weekend is a contentious but well described phenomenon. However, it remains uncertain whether adverse outcomes, including prolonged hospital length-of-stay (LOS), may also occur after patients undergoing major planned surgery are admitted to an intensive care unit (ICU) out-of-office-hours, either during weeknights (after 18:00) or on weekends. METHODS: All planned surgical admissions requiring admission to one of 183 ICUs across Australia and New Zealand between 2006 and 2016 were included in this retrospective population-based cohort study. Primary outcomes were hospital LOS and hospital mortality. RESULTS: Of the total 504 713 planned postoperative ICU admissions, 33.6% occurred during out-of-office hours. After adjusting for available risk factors, out-of-office-hours ICU admissions were associated with a significant increase in hospital LOS [+2.6 days, 95% confidence interval (CI) 2.5-2.6], mortality [odd ratio (OR) 1.5, 95%CI 1.4-1.6], and a reduced chance of being directly discharged home (OR 0.8, 95%CI 0.8-0.8). The strongest association for adverse outcomes occurred with weekend ICU admissions (hospital LOS: +3.0 days, 95%CI 3.2-3.6; hospital mortality: OR 1.7, 95%CI 1.6-1.8). Clustering of adverse outcomes by hospitals was not observed in the generalised estimating equation analyses. CONCLUSIONS: Despite a greater clinical staff availability and higher monitoring levels, planned surgery requiring anticipated out-of-office-hours ICU admission was associated with a prolonged hospital LOS, reduced discharge directly home, and increased mortality compared with in-office-hours admissions. Our findings have potential clinical, economic and health policy implications on how complex planned surgery should be planned and managed. PMID- 29793608 TI - Fit for surgery? Evidence supporting prehabilitation programs. PMID- 29793606 TI - The anion study: effect of different crystalloid solutions on acid base balance, physiology, and survival in a rodent model of acute isovolaemic haemodilution. AB - BACKGROUND: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes. METHODS: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function. RESULTS: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups. CONCLUSIONS: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model. PMID- 29793610 TI - Difficult paediatric airways-what to do? PMID- 29793609 TI - Attempting tracheal intubation without paralysis. PMID- 29793611 TI - Education: the last mile to universal videolaryngoscopy. PMID- 29793612 TI - Another nail in the saline coffin. PMID- 29793613 TI - Over-delivery of desflurane via Aisys Carestation Aladin2 CassetteTM vaporiser. PMID- 29793614 TI - Occupational exposure to methoxyflurane administered for procedural sedation: an observational study of 40 exposures. PMID- 29793615 TI - Safety of subsequent general anaesthesia in patients allergic to neuromuscular blocking agents: value of allergy skin testing. PMID- 29793616 TI - Alfaxalone and comments on: Thiopental to desflurane-an anaesthetic journey. Where are we going next? [Br J Anaesth 2017;119:i44-52]. PMID- 29793617 TI - Corrigendum to 'Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis' [Br J Anaesth 2018; 120: 37-50]. PMID- 29793618 TI - Research Techniques Made Simple: Mass Spectrometry for Analysis of Proteins in Dermatological Research. AB - Identifying previously unknown proteins or detecting the presence of known proteins in research samples is critical to many experiments conducted in life sciences, including dermatology. Sensitive protein detection can help elucidate new intervention targets and mechanisms of disease, such as in autoimmune blistering skin diseases, atopic eczema, or other conditions. Historically, peptides from highly purified single proteins were sequenced, with many limitations, by stepwise degradation from the N-terminus to the C-terminus with subsequent identification by UV absorbance spectroscopy of the released amino acids (i.e., Edman degradation). Recently, however, the availability of comprehensive protein databases from different species (derived from high throughput next-generation sequencing of those organisms' genomes) and sophisticated bioinformatics analysis tools have facilitated the development and use of mass spectrometry for identification and global analysis of proteins, summarized as mass spectrometry-based proteomics. Mass spectrometry is an analytical technique measuring the mass (m)-to-charge (z) ratio of ionized biological molecules such as peptides. Proteins can be identified by correlating peptide-derived experimental mass spectrometry spectra with theoretical spectra predicted from protein databases. Here we briefly describe how this technique works, how it can be used for identification of proteins, and how this knowledge can be applied in elucidating human biology and disease. PMID- 29793619 TI - Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid. AB - Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes. PMID- 29793620 TI - A Hairy Tale of Monocytes and Contact Hypersensitivity Reactions. AB - Hair follicles have recently emerged as immunologically active organs that orchestrate recruitment and trafficking of immune cells within skin. Liu et al. (2018) expand our knowledge in this growing area of research by characterizing the network of immune cell interactions during experimental contact hypersensitivity that, interestingly, is centered around hair follicles. PMID- 29793621 TI - Cooling the Itch via TRPM8. AB - Cooling is an effective temporary remedy for itch, bringing welcome relief to itchy insect bites, nettle stings, poison ivy, atopic dermatitis, and psoriasis. Menthol, causing a cooling sensation, has similar itch-relieving effects. Palkar et al. demonstrate that TRPM8, a menthol- and cold-activated ion channel, is essential for cooling to relieve itch, suggesting that pharmacologic TRPM8 activation should be explored further as an antipruritic strategy. PMID- 29793622 TI - Hair Regeneration under Stress. AB - The phenomenon of wound-induced hair neogenesis in adult mice and rabbits offers a tantalizing window into the mechanisms of regeneration. By comparing wounds in mice and several rat strains, Guerrero-Juarez et al. attempted to identify factors that may contribute to the failure of wound-induced hair neogenesis to occur in the rat. In addition to biochemical, cellular, and molecular variation, worthwhile comparisons could include the magnitude, distribution, and source of tensional forces within the wound environment. PMID- 29793623 TI - Erratum. PMID- 29793624 TI - Erratum. PMID- 29793625 TI - SnapshotDx Quiz: June 2018. PMID- 29793626 TI - Cells to Surgery Quiz: June 2018. PMID- 29793627 TI - Smartwatches in the Fight Against Atrial Fibrillation: The Little Watch That Could. PMID- 29793628 TI - Targeting Inflammation in the Prevention and Treatment of Type 2 Diabetes: Insights From CANTOS. PMID- 29793630 TI - Cardiovascular Risk Reduction in Patients With Chronic Kidney Disease: Potential for Targeting Inflammation With Canakinumab. PMID- 29793629 TI - Inhibition of Interleukin-1beta by Canakinumab and Cardiovascular Outcomes in Patients With Chronic Kidney Disease. AB - BACKGROUND: Inflammation contributes to chronic kidney disease (CKD), in part mediated through activation of interleukin (IL)-1beta by the NLRP3 inflammasome within the kidney. This process also likely contributes to the accelerated atherosclerosis associated with nephropathy. OBJECTIVES: The authors hypothesized that canakinumab, a human monoclonal antibody targeting IL-1beta, might reduce cardiovascular event rates and improve renal function among post-myocardial infarction patients with CKD. METHODS: Stable post-myocardial infarction patients with high-sensitivity C-reactive protein (hsCRP) >= 2mg/l were randomly allocated to placebo or to 1 of 3 doses of canakinumab (50, 150, or 300 mg) given subcutaneously once every 3 months. Participants were followed for incident myocardial infarction, stroke, hospitalization for unstable angina requiring urgent revascularization, cardiovascular death, or death from any cause over a median follow-up period of 3.7 years (maximum 5 years). All patients additionally had serial monitoring of estimated glomerular filtration rate (eGFR), creatinine, the urine albumin to creatinine ratio (uACR), and were monitored for adverse renal and urinary events. RESULTS: Of 10,061 participants, 1,875 (18.6%) had baseline eGFR <60 ml/min/1.73 m2. These moderate CKD patients had higher incidence rates for major adverse vascular events compared with those with eGFR >=60 ml/min/1.73 m2 (6.92 vs. 4.13 per 100 person-years; p < 0.0001). Random allocation to canakinumab reduced the risk of major adverse cardiovascular events among those with CKD (hazard ratio: 0.82; 95% confidence interval: 0.68 to 1.00; p = 0.05) with the largest cardiovascular benefits accruing among those who achieved on-treatment hsCRP levels below 2 mg/l measured after taking the first dose (hazard ratio: 0.68; 95% confidence interval: 0.53 to 0.86; p = 0.0015). Comparable effects were observed among those with baseline albuminuria or diabetes. Canakinumab had neither clinically meaningful benefits nor substantive harms with respect to serial measures of eGFR, creatinine, the uACR, or reported adverse renal events during trial follow-up. CONCLUSIONS: IL-1beta inhibition with canakinumab reduces major adverse cardiovascular event rates among high-risk atherosclerosis patients with CKD, particularly among those with a robust anti inflammatory response to initial treatment. These cardiovascular benefits accrued with no adverse clinical renal events. (Canakinumab Anti-inflammatory Thrombosis Outcomes Study [CANTOS]; NCT01327846). PMID- 29793632 TI - How to Predict Pregnancy Risk in an Individual Woman With Heart Disease. PMID- 29793631 TI - Pregnancy Outcomes in Women With Heart Disease: The CARPREG II Study. AB - BACKGROUND: Identifying women at high risk is an important aspect of care for women with heart disease. OBJECTIVES: This study sought to: 1) examine cardiac complications during pregnancy and their temporal trends; and 2) derive a risk stratification index. METHODS: We prospectively enrolled consecutive pregnant women with heart disease and determined their cardiac outcomes during pregnancy. Temporal trends in complications were examined. A multivariate analysis was performed to identify predictors of cardiac complications and these were incorporated into a new risk index. RESULTS: In total, 1,938 pregnancies were included. Cardiac complications occurred in 16% of pregnancies and were primarily related to arrhythmias and heart failure. Although the overall rates of cardiac complications during pregnancy did not change over the years, the frequency of pulmonary edema decreased (8% from 1994 to 2001 vs. 4% from 2001 to 2014; p value = 0.012). Ten predictors of maternal cardiac complications were identified: 5 general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions); 4 lesion specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease); and 1 delivery of care predictor (late pregnancy assessment). These 10 predictors were incorporated into a new risk index (CARPREG II [Cardiac Disease in Pregnancy Study]). CONCLUSIONS: Pregnancy in women with heart disease continues to be associated with significant morbidity, although mortality is rare. Prediction of maternal cardiac complications in women with heart disease is enhanced by integration of general, lesion-specific, and delivery of care variables. PMID- 29793634 TI - Public Health Approach to Decrease Mortality for Congenital Heart Defects: Dying Too Soon. PMID- 29793635 TI - Antithrombotic Therapy for Peripheral Artery Disease: Recent Advances. AB - Peripheral artery disease (PAD) affects over 200 million people globally and is a cause of significant morbidity, mortality, and disability due to limb loss. Although secondary prevention with antithrombotic therapy is a mainstay of treatment to prevent adverse cardiovascular events, PAD patients are often undertreated with antithrombotic agents. Furthermore, there is a paucity of high quality data from randomized controlled trials of PAD patients, leading to wide variations in clinical practice and guideline recommendations. Recently, there have been important advances that have further increased the number of antiplatelet and anticoagulant choices potentially available for patients with PAD. In this context, this paper aims to summarize the current available evidence for the safety and efficacy of various antithrombotic agents in PAD, and discuss how to integrate this emerging evidence into actual clinical practice. An evidenced-based approach to PAD patients is essential to achieve optimal outcomes, weighing cardiovascular and limb benefits against bleeding risks. PMID- 29793633 TI - Trends in Long-Term Mortality After Congenital Heart Surgery. AB - BACKGROUND: Congenital heart surgery has improved the survival of patients with even the most complex defects, but the long-term survival after these procedures has not been fully described. OBJECTIVES: The purpose of this study was to evaluate the long-term survival of patients (age <21 years) who were operated on for congenital heart defects (CHDs). METHODS: This study used the Pediatric Cardiac Care Consortium data, a U.S.-based, multicenter registry of pediatric cardiac surgery. Survival analysis included 35,998 patients who survived their first congenital heart surgery at <21 years of age and had adequate identifiers for linkage with the National Death Index through 2014. Survival was compared to that in the general population using standardized mortality ratios (SMRs). RESULTS: After a median follow-up of 18 years (645,806 person-years), 3,191 deaths occurred with an overall SMR of 8.3 (95% confidence interval [CI]: 8.0 to 8.7). The 15-year SMR decreased from 12.7 (95% CI: 11.9 to 13.6) in the early era (1982 to 1992) to 10.0 (95% CI: 9.3 to 10.8) in the late era (1998 to 2003). The SMR remained elevated even for mild forms of CHD such as patent ductus arteriosus (SMR 4.5) and atrial septal defects (SMR 4.9). The largest decreases in SMR occurred for patients with transposition of great arteries (early: 11.0 vs. late: 3.8; p < 0.05), complete atrioventricular canal (31.3 vs. 15.3; p < 0.05), and single ventricle (53.7 vs. 31.3; p < 0.05). CONCLUSIONS: In this large U.S. cohort, long-term mortality after congenital heart surgery was elevated across all forms of CHD. Survival has improved over time, particularly for severe defects with significant changes in their management strategy, but still lags behind the general population. PMID- 29793636 TI - Chronic Thromboembolic Pulmonary Hypertension: Evolving Therapeutic Approaches for Operable and Inoperable Disease. AB - Chronic thromboembolic pulmonary hypertension (CTEPH), a rare consequence of an acute pulmonary embolism, is a disease that is underdiagnosed, and surgical pulmonary thromboendarterectomy (PTE) remains the preferred therapy. However, determination of operability is multifactorial and can be challenging. There is growing excitement for the percutaneous treatment of inoperable CTEPH with data from multiple centers around the world showing the clinical feasibility of balloon pulmonary angioplasty. Riociguat remains the only approved medical therapy for CTEPH patients deemed inoperable or with persistent pulmonary hypertension after PTE. We recommend that expert multidisciplinary CTEPH teams be developed at individual institutions. Additionally, optimal and standardized techniques for balloon pulmonary angioplasty need to be developed along with dedicated interventional equipment and appropriate training standards. In the meantime, the percutaneous revascularization option is appropriate for patients deemed inoperable in combination with targeted medical therapy, or those who have failed to benefit from surgery. PMID- 29793637 TI - Impact of C-Reactive Protein and Coronary Artery Calcium on Benefit Observed With Atorvastatin. PMID- 29793638 TI - SAVR Versus TAVR Outcomes in Patients With Prior History of Stroke. PMID- 29793639 TI - Cardiovascular Risk Models and Statin Therapy. PMID- 29793640 TI - Reply: Cardiovascular Risk Models and Statin Therapy. PMID- 29793641 TI - Missed Opportunities in Cardiac Arrest: The Promise of 24/7 Ongoing On-Site Interventional Cardiologist Availability. PMID- 29793642 TI - Off-Hours and In-Hospital Mortality: Lower Resources or Higher Severity? PMID- 29793643 TI - Reply: Lower Survival for In-Hospital Cardiac Arrests During Nights and Weekends. PMID- 29793644 TI - Correction. PMID- 29793645 TI - Perspectives on Acquired Resistance to PD-1 Axis Inhibitors in Patients with Non Small Cell Lung Cancer. PMID- 29793646 TI - Making Lung Cancer Clinical Trials More Inclusive: Recommendations for Expanding Eligibility Criteria. PMID- 29793647 TI - Atezolizumab after Nivolumab-Induced Inflammatory Polyarthritis: Can Anti-PD-L1 Immunotherapy Be Administered after Anti-PD-1-Related Immune Toxicities? PMID- 29793649 TI - Risk of Second Lung Cancer in ITALUNG LDCT Screening. PMID- 29793648 TI - Targeted Therapy and Immunotherapy Lead to Rapid Regression of Advanced Non-Small Cell Lung Cancer with Multiple Driver Mutations. PMID- 29793650 TI - Risk of Second Lung Cancer in Patients With Previously Treated Lung Cancer: Analysis of Surveillance, Epidemiology, and End Results Data. PMID- 29793651 TI - EGFR exon 18 DelE709_T710insD as an Acquired Resistance Mechanism to Afatinib in an Advanced EGFR exon 18 E709H Lung Adenocarcinoma. PMID- 29793652 TI - Miliary Adenocarcinoma of the Lung Responds to Gefitinib and Afatinib. PMID- 29793653 TI - Real-world Outcomes of Multiple Myeloma: Retrospective Analysis of the Czech Registry of Monoclonal Gammopathies. AB - INTRODUCTION: Real-world data on patient outcomes and treatment patterns in multiple myeloma (MM) are limited. MATERIALS AND METHODS: The present noninterventional, observational, retrospective analysis of prospectively collected Czech patient medical record data from the Registry of Monoclonal Gammopathies estimated real-world outcomes in adults with a diagnosis of symptomatic MM made between May 2007 and June 2014. RESULTS: In total, 2446 patients had initiated first-line treatment. The median overall survival since the diagnosis (primary endpoint) was 50.3 months (95% confidence interval, 46.1 54.5 months) and decreased with each successive treatment line. A similar trend was observed for progression-free survival and the depth of response. In line with European guidelines and clinical practice, bortezomib-, thalidomide-, and lenalidomide-based regimens were most commonly used across all treatment lines (42.3%, 28.9%, and 18.4%, respectively). In the first line, bortezomib and thalidomide were used most often, with lenalidomide the most commonly used agent in the relapse setting (second to fourth lines). Exploratory analyses revealed that younger age (<= 65 years), lower international staging system stage, and previous stem cell transplantation were associated with significant improvements in overall and progression-free survival, especially in the early treatment lines. CONCLUSION: The present study is the first analysis of Czech data from the Registry of Monoclonal Gammopathies, and it provides important insights into the real-world management of MM for physicians and healthcare providers. PMID- 29793654 TI - Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk. AB - BACKGROUND: Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk. MATERIALS AND METHODS: The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts. RESULTS: We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene. CONCLUSION: Taken together, our findings suggest a potential role for NER in CRC. PMID- 29793655 TI - Introduction to the special issue on endocrine disrupting chemicals and behavior. PMID- 29793656 TI - A case of recipient-derived pulmonary Kaposi sarcoma after bilateral lung transplantation. PMID- 29793657 TI - Ultrasonography of the optic nerve: An effective and easy strategy for detecting intracranial hypertension. PMID- 29793658 TI - Magnesium: An Important Orphan. PMID- 29793659 TI - Magnesium Homeostasis in CKD. PMID- 29793660 TI - Magnesium Balance and Measurement. AB - Magnesium is an essential ion in the human body, playing an important role in practically every major metabolic and biochemical process, supporting and maintaining cellular processes critical for human life. Magnesium plays an important physiological role, particularly in the brain, heart, and skeletal muscles. As the second most abundant intracellular cation after potassium, it is involved in over 600 enzymatic reactions including energy metabolism and protein synthesis. Magnesium has been implicated in and used as treatment of several diseases. Although the importance of magnesium is widely acknowledged, routine serum magnesium levels are not routinely evaluated in clinical medicine. This review provides a discussion as to where magnesium is stored, handled, absorbed, and excreted. We discuss approaches for the assessment of magnesium status. PMID- 29793661 TI - Dietary Magnesium and Chronic Disease. AB - Although official magnesium (Mg) dietary reference intakes are open to question, a significant number of adults likely have intakes that are in the range of 50% 99% of the requirement. This moderate or marginal (subclinical) deficient Mg intake generally is asymptomatic. Animal studies, however, indicate that moderate or subclinical Mg deficiency primes phagocytic cells for the release of proinflammatory cytokines leading to chronic inflammatory and oxidative stress. Human studies have found that dietary Mg is inversely related to serum or plasma C-reactive protein (CRP). Individuals with apparently deficient Mg intakes have an increased likelihood of serum or plasma CRP >=3.0 mg/L, considered an indicator of chronic inflammatory stress that increases the risk for chronic disease. In addition, elevated serum or plasma CRP in individuals with chronic disease is decreased by Mg supplementation, which suggests that Mg decreases the risk for chronic disease. The importance of dietary Mg intake on the risk for chronic disease through affecting inflammatory and oxidative stress is supported by numerous meta-analyses and systematic reviews that have found dietary Mg is inversely associated with chronic diseases such hypertension, ischemic heart disease, stroke, metabolic syndrome, diabetes, and colorectal cancer. PMID- 29793662 TI - Magnesium Handling in the Kidney. AB - Magnesium is a divalent cation that fills essential roles as regulator and cofactor in a variety of biological pathways, and maintenance of magnesium balance is vital to human health. The kidney, in concert with the intestine, has an important role in maintaining magnesium homeostasis. Although micropuncture and microperfusion studies in the mammalian nephron have shone a light on magnesium handling in the various nephron segments, much of what we know about the protein mediators of magnesium handling in the kidney have come from more recent genetic studies. In the proximal tubule and thick ascending limb, magnesium reabsorption is believed to occur primarily through the paracellular shunt pathway, which ultimately depends on the electrochemical gradient setup by active sodium reabsorption. In the distal convoluted tubule, magnesium transport is transcellular, although magnesium reabsorption also appears to be related to active sodium reabsorption in this segment. In addition, evidence suggests that magnesium transport is highly regulated, although a specific hormonal regulator of extracellular magnesium has yet to be identified. PMID- 29793663 TI - Magnesium and Blood Pressure: A Physiology-Based Approach. AB - Hypertension is an important public health challenge because of its high prevalence and strong association with cardiovascular disease and premature death. Hypertension is a major cause of CKD, is present in more than 80% of CKD patients, and contributes to CKD progression. Risk factors for hypertension include, but are not limited to, age, race, family history, obesity, physical inactivity, tobacco use, and inadequate intake of minerals such as calcium, potassium, and magnesium. Magnesium is the second most abundant intracellular cation in the human body and plays an important role in insulin and adenosine triphosphate metabolism. Low dietary magnesium intake has been associated with an increased risk of developing hypertension in prospective cohort studies. Moreover, clinical trials suggest that magnesium supplementation has blood pressure-lowering effects. In addition, emerging data reveal potential mechanisms by which magnesium may influence blood pressure. Here, we will review these mechanisms, using a physiology-based approach, focusing on the effects of magnesium on total peripheral resistance and cardiac output. PMID- 29793664 TI - Magnesium and Cardiovascular Disease. AB - Magnesium is the most abundant intracellular divalent cation and essential for maintaining normal cellular physiology and metabolism, acting as a cofactor of numerous enzymes, regulating ion channels and energy generation. In the heart, magnesium plays a key role in modulating neuronal excitation, intracardiac conduction, and myocardial contraction by regulating a number of ion transporters, including potassium and calcium channels. Magnesium also has a role in regulating vascular tone, atherogenesis and thrombosis, vascular calcification, and proliferation and migration of endothelial and vascular smooth muscle cells. As such, magnesium potentially has a major influence on the pathogenesis of cardiovascular disease. As the kidney is a major regulator of magnesium homeostasis, kidney disorders can potentially lead to both magnesium depletion and overload, and as such increase the risk of cardiovascular disease. Observational data have shown an association between low serum magnesium concentrations or magnesium intake and increased atherosclerosis, coronary artery disease, arrhythmias, and heart failure. However, major trials of supplementation with magnesium have reported inconsistent benefits and also raised potential adverse effects of magnesium overload. As such, there is currently no firm recommendation for routine magnesium supplementation except when hypomagnesemia has been proven or suspected as a cause for cardiac arrhythmias. PMID- 29793665 TI - Oral Magnesium Supplementation and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial. AB - The objective of the study was to evaluate the efficacy of oral magnesium supplementation in the improvement of metabolic syndrome (MetS) and its components. This is a randomized double-blind, placebo-controlled clinical trial that enrolled 198 individuals with MetS and hypomagnesemia who were randomly allocated to receive either 30 mL of magnesium chloride 5% solution, equivalent to 382 mg of elemental magnesium (n = 100), or placebo solution (n = 98), daily for 16 weeks. Serum magnesium levels <1.8 mg/dL defined hypomagnesemia. At final conditions, a total of 48 (48%) and 76 (77.5%) individuals had MetS in the magnesium and placebo groups (P = 0.01), respectively. At baseline, percent of individuals with 3, 4, and 5 criteria of MetS in the magnesium group were 60.0%, 37.0%, and 3.0%, respectively, and in the control group 55.1%, 35.7%, and 9.2%, respectively. Between basal and final conditions, changes in the components of MetS were significantly higher in the magnesium than placebo groups: -3.6 +/- 3.3 mmHg, P = 0.001 for systolic blood pressure; -5.5 +/- 1.7 mmHg, P = 0.005 for diastolic blood pressure; -12.4 +/- 3.6 mg/dL, P < 0.005 for fasting glucose; 61.2 +/- 24 mg/dL, P = 0.003 for triglycerides; and 0.9 +/- 0.4 mg/dL, P = 0.06 for high-density lipoprotein cholesterol. Magnesium supplementation improves MetS by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. PMID- 29793666 TI - Magnesium and Drugs Commonly Used in Chronic Kidney Disease. AB - As with other electrolytes, magnesium homeostasis depends on the balance between gastrointestinal absorption and kidney excretion. Certain drugs used commonly in patients with CKD can decrease gastrointestinal ingestion and kidney reclamation, and potentially cause hypomagnesemia. Other magnesium-containing drugs such as laxatives and cathartics can induce hypermagnesemia, particularly in those with impaired glomerular filtration and magnesium excretion. In this review, we will discuss the potential magnesium complications associated with a range of commonly encountered drugs in the care of CKD patients, discuss the potential mechanisms, and provide basic clinical recommendations. PMID- 29793667 TI - Magnesium and Progression of Chronic Kidney Disease: Benefits Beyond Cardiovascular Protection? AB - Experimental and clinical studies have demonstrated that magnesium deficiency leads to hypertension, insulin resistance, and endothelial dysfunction, and is associated with an increased risk of cardiovascular events. Given that cardiovascular disease and CKD share similar risk factors, the low magnesium status may also contribute to CKD progression. In fact, lower serum magnesium levels and lower dietary magnesium intake are associated with an increased risk of incident CKD and progression to end-stage kidney disease. Because these associations are independent of traditional risk factors, other pathways might be involved in the relationship between magnesium deficiency and the risk of CKD progression. Recent evidence has shown that magnesium suppresses phosphate induced vascular calcification. Magnesium impairs the crystallization of calcium phosphate-more specifically, the maturation of calciprotein particles. Considering that phosphate overload causes kidney damage, magnesium might counteract the phosphate toxicity to the kidney, as in the case of vascular calcification. This hypothesis is supported by an in vitro observation that magnesium alleviates proximal tubular cell injury induced by high phosphate. Potential usefulness of magnesium as a treatment option for phosphate toxicity in CKD should be further investigated by intervention studies. PMID- 29793668 TI - Magnesium as a Calcification Inhibitor. AB - Vascular calcification (VC) is associated with elevated cardiovascular mortality rates in patients with CKD. Recent clinical studies of patients with advanced CKD have observed an association between low serum magnesium (Mg) levels on one hand and elevated VC and cardiovascular mortality on the other. These findings have stimulated interest in understanding Mg's impact on CKD in general and the associated VC in particular. In vitro and preclinical in vivo data indicate that Mg has the potential to protect vascular smooth muscle cells against calcification via several different molecular mechanisms. Accordingly, data from pilot interventional studies in the clinic suggest that oral Mg supplementation reduces VC in patients with CKD. The present review provides an overview of our current understanding of the impact of Mg on the development of VC in patients with CKD. PMID- 29793669 TI - Magnesium Balance in Chronic and End-Stage Kidney Disease. AB - This article explores the effects of CKD and end-stage kidney disease on magnesium balance. In CKD, there is decreased glomerular filtration of magnesium. Decreased tubular reabsorption can compensate to a degree, but once CKD stage 4 is reached there is a tendency toward hypermagnesemia. In dialysis, magnesium balance is dependent on the constituents of the dialysate that the blood is exposed to. The concentration of dialysate magnesium is just one of the factors that need to be considered. During transplantation, there are particular effects of immunosuppressants that can affect the magnesium balance and need to be considered by the clinician. PMID- 29793670 TI - Renal Functional Reserve Revisited. AB - Kidney function, like the function of other organs, is dynamic and continuously adjusts to changes in the internal environment to maintain homeostasis. The glomerular filtration rate, which serves as the primary index of kidney function in clinical practice, increases in response to various physiological and pathological stressors including oral protein intake. The difference between the glomerular filtration rate in the resting state and at maximum capacity has been termed renal functional reserve (RFR). RFR could provide additional information on kidney health and renal function prognosis. Despite longstanding interest in RFR as a biomarker in nephrology, its underlying mechanisms remain inadequately understood. Moreover, no consensus has been reached on how it should be quantified. Previous studies on RFR have used various measurement methods and yielded heterogeneous results. A standardized and clinically feasible approach to quantifying RFR would allow for more rigorous appraisal of its value as a biomarker and could pave the way for adoption of "renal stress tests" into clinical practice. PMID- 29793671 TI - [Cardiovascular consequences of chronic kidney disease, impact of modulation of epoxyeicosatrienoic acids]. AB - Cardiovascular events are more prevalent in chronic kidney disease than in the general population, being the main cause of morbi-mortality. The physiopathology explaining this association remains complex. Thus, research for new therapies to prevent cardiovascular events in chronic kidney disease is a major issue. Epoxyeicosatrienoic acids, products of the arachidonic acid metabolism, are endothelium-derived hyperpolarizing factors with vasodilatory, anti-inflammatory, thrombolytic, pro-angiogenic and anti-apoptotic properties. A decrease in the bioavailability of epoxyeicosatrienoic acids has been observed in many cardiovascular diseases such as hypertension, myocardial infarction or diabetes. Moreover, human studies of genetic polymorphisms of soluble epoxide hydrolase, the enzyme degrading epoxyeicoatrienoic acids, have shown that allelic variants related to an increase in its activity is associated with higher risk of cardiovascular events. Modulation of epoxyeicosatrienoic acids by soluble epoxide hydrolase inhibitors in some cardiovascular diseases induces structural improvements in the heart, vessels and kidneys, including decrease in cardiomyocyte hypertrophy, reduction in cardiac and renal interstitial fibrosis, improvement in renal hemodynamics, and prevention of endothelial dysfunction. In this context, increasing the bioavailability of epoxyeicosatrienoic acids appears to be an interesting therapeutic option in the prevention of cardiovascular events related to chronic kidney disease. PMID- 29793672 TI - [PASTIS study: Evaluation of an automated office blood pressure measurement]. AB - OBJECTIVE: The evaluation of automated office blood pressure (AOBP) measurement compared to 24-hour ambulatory BP monitoring (ABPM), Home BP measurement and manual BP. PATIENTS AND METHODOLOGY: A total of 123 hypertensive patients were included. Overall, 68 completed the 4 measurement: Manual BP in the office (Omron 705 CP 3 measurements), ABPM (Spacelab of 96 measurement/per 24hours), Home BP (18 measurement during 3 days), AOBP using the SPRINT methodology: lying patient, isolated with an automatic measurement (Dinamap) every minutes during 8minutes (average of the last 3 measurement). Twenty-two out of 123 patients (26%) did not complete the Home BP measurement. RESULTS: The average of AOBP measurement using SPRINT is 132+/-12/69+/-9mmHg, of ABPM 134+/-13/79+/-9, of Home BP: 135+/-13/70+/ 13 and of manual BP: 138+/-13/72+/-11mmHg The Bland & Altman method highlight that the AOBP, the ABPM and home BP measurement are 3 substitutable methods. The confidence interval is smaller between the ABPM and the AOBP than with the home BP. CONCLUSION: The automated office blood pressure, as the Home BP measurement, can be considered a reliable substitute for the ABPM, when the later is not accessible, and when a repeated therapeutic evaluation is needed, or when the home BP measurement is not done. These results encourage us to use it more frequently as the Canadian Hypertension Education Program recommend it. PMID- 29793673 TI - [Reasons for deciding to die in hospital or at home. The vision of professionals]. AB - OBJECTIVE: To discover the reasons for deciding to die in hospital or at home, from the perspective of professionals involved. METHOD: Qualitative phenomenological study. Intentional sample. Four multidisciplinary focus groups were held, two in hospitals and two in primary care centres in Seville (Spain). Twenty-nine professionals with at least two years experience in the care of people with a terminal disease participated, following the theoretical saturation of information criterion. RESULTS: Responses from the first script were gathered in three core categories: patient and the family, professionals and care process. Patients are generally not asked about their preferences as to where they wish to die, and if their family is not aware of their preference, it is not possible to carry out advanced planning of care. Families tend to choose the hospital because of the possibility of monitoring and resources in primary care. Professionals are trained in how to approach death, but they do not feel sufficiently prepared and focus on the clinical and administrative issues. The care process favours oncology patients because it is easier to identify their illness as terminal. Resources are not equal and interlevel communication needs to be improved. The family's involvement in the process is not facilitated, which impedes their decision-making. CONCLUSIONS: Advance care planning and use of the advance directive should be promoted, as well as, interlevel communication and coordination, supply resources, especially in primary care, and professionals should receive training on how to approach death.. The patient's family should be involved in the care process and provided the necessary support. PMID- 29793674 TI - Early Identification and Management of Sepsis in Nursing Facilities: Challenges and Opportunities. PMID- 29793675 TI - Frailty Defined by FRAIL Scale as a Predictor of Mortality: A Systematic Review and Meta-analysis. AB - OBJECTIVES: To conduct a systematic review of the literature on prospective cohort studies examining mortality risk according to frailty defined by FRAIL scale, and to perform a meta-analysis to synthesize the pooled risk estimates. DESIGN: Systematic review and meta-analysis. SETTING: Embase, Scopus, MEDLINE, CINAHL, and PsycINFO were systematically searched in March 2018. References of included studies were reviewed and a forward citation tracking was performed on relevant review papers for additional studies. Additional data necessary for a meta-analysis were requested from corresponding authors. PARTICIPANTS: Community dwelling middle-aged and older adults. MEASUREMENTS: Mortality risk due to frailty as defined by the FRAIL scale. RESULTS: After removing duplicates, there are 81 citations for title, abstract, and full-text screening. Eight studies were included in this review. Four studies calculated the area under the receiver operating characteristic curve, which ranged from 0.54 to 0.70. A random-effects meta-analysis was conducted on 3 studies that provided adjusted hazard ratios (HRs) of mortality risk according to 3 frailty groups (robust, prefrail, and frail) defined by FRAIL scale. Both frailty and prefrailty were significantly associated with higher mortality risk than robustness [pooled HR = 3.53, 95% confidence interval (CI) = 1.66-7.49, P = .001; pooled HR = 1.75, 95% CI = 1.14 2.70, P = .01, respectively]. No evidence of publication bias was observed. CONCLUSION: This study demonstrated that FRAIL scale is a tool that can effectively identify frailty/prefrailty status, as well as quantify frailty status in a graded manner in relation to mortality risk. Although its feasibility is of note, not many studies are yet using this relatively new tool. More studies are warranted regarding mortality and other health outcomes. PMID- 29793676 TI - Introduction: Management of infected aortic pathology. PMID- 29793677 TI - Efficacy of cord blood platelet gel application for enhancing diabetic foot ulcer healing after lower limb revascularization. AB - The efficacy of umbilical cord blood platelet gel (CBPG) application on healing foot ulcers was analyzed in 10 diabetic patients treated for critical lower limb ischemia by surgical or endovascular arterial revascularization. During a 9-month period, 20 diabetic patients affected by critical lower limb ischemia with tissue loss were enrolled in this nonblinded, consecutive series, randomized clinical trial. After clinical evaluation, patients underwent endovascular or surgical revascularization of the affected limb, followed by minor amputations or surgical debridement of ischemic lesions. Patients were then randomly divided into two groups: 10 patients in Group A treated with standard wound care and 10 patients in Group B treated with topic application of CBPG. The CBPG protocol consisted of platelet gel application twice a week for 4 weeks and then once a week for an additional 4 weeks. Healing was assessed by direct ulcer dimension tracing onto clear plastic sheet and subsequent computerized planimetry. The mean pretreatment and post-treatment ulcer areas at 30 days for Group A were 15.1 cm2 and 8.1 cm2, respectively, and for Group B were 15.7 cm2 and 3.25 cm2, respectively; resulting in a mean ulcer area reduction of 46% for Group A and 79% for Group B patients (P < .01). These observations suggest CBPG application can promote more rapid wound healing than standard care, and indicate the need for a randomized, multicenter trial to confirm clinical efficacy. PMID- 29793678 TI - Idiopathic lobular granulomatous mastitis: radiological management in two cases. PMID- 29793680 TI - Problems, perceptions and actions: An interdependent process for generating informal social control. AB - Using two waves of survey data for residents in neighborhoods in Brisbane, this study explores the interdependent relationship between residents' perceptions of neighboring, cohesion, collective efficacy, neighborhood disorder, and the actions they take to address these problems. Our longitudinal results show that residents' perceived severity of a problem helps explain engaging in activity to address the problem. People loitering appeared to be the most galvanizing problem for residents, but had particularly deleterious effects on perceptions of cohesion and collective efficacy. We also find that residents who perceive more neighboring in their local area engage in more public and parochial social control activity and residents who live in collectively efficacious neighborhoods are more likely to engage in parochial social control action. Furthermore, residents who themselves perceive more collective efficacy in the neighborhood engage in more parochial or public social control during the subsequent time period. Importantly, we find strong evidence that residents update their sense of collective efficacy. Perceiving more problems in the neighborhood, and perceiving that these problems are increasing, reduced perceptions of neighboring and collective efficacy over time. PMID- 29793679 TI - Ecologically unequal exchange, recessions, and climate change: A longitudinal study. AB - This study investigates how the ecologically unequal exchange of carbon dioxide emissions varies with economic recessions. I propose a country-specific approach to examine (1) the relationship between carbon dioxide emissions in developing countries and the "vertical flow" of exports to the United States; and (2) the variations of the relationship before, during, and after two recent economic recessions in 2001 and 2008. Using data on 69 developing nations between 2000 and 2010, I estimate time-series cross-sectional regression models with two-way fixed effects. Results suggest that the vertical flow of exports to the United States is positively associated with carbon dioxide emissions in developing countries. The magnitude of this relationship increased in 2001, 2009, and 2010, and decreased in 2008, but remained stable in non-recession periods, suggesting that economic recessions in the United States are associated with variations of ecologically unequal exchange. Results highlight the impacts of U.S. recessions on carbon emissions in developing countries through the structure of international trade. PMID- 29793681 TI - Does community social embeddedness promote generalized trust? An experimental test of the spillover effect. AB - Despite the theoretical relevance attributed to the spillover effect, little empirical research has focused on testing its causal validity. Addressing this gap in the literature, I propose a novel experimental design to test if the overall density of social links in a community promotes trustworthy and trusting behaviors with absolute strangers. Controlling for social integration (i.e. the individual number of social connections), I found that density fosters higher levels of trust. In particular, results show that people in denser communities are more likely to trust their unknown fellow citizens, encouraging isolated subjects to engage with strangers. However, evidence did not support the idea that community social embeddedness causes an increase of trustworthiness, indicating that the spillover effect works only with respect to trust. PMID- 29793682 TI - Migration and protest in the Jim Crow South. AB - The Great Migration and the Civil Rights Movement were two pivotal events experienced by the southern African American population during the 20th Century. Each has received considerable attention by social scientists and historians, and a possible connection between the two phenomena has been speculated. However, no systematic investigation of the effect of migration on protest during the Jim Crow era has been conducted. In this study we use data for 333 southern communities to examine the relationship between youthful black migration between 1950 and 1960 and the occurrence of sit-ins early in 1960. We find a strong positive, non-linear, relationship between net-migration and the likelihood of a sit-in which can be explained by two sets of mediating influences: local demographic conditions and local organizational presence. Our findings offer strong empirical support for an association between southern black migration and protest during Jim Crow and suggest the value of considering the influence of demographic forces on collective action. PMID- 29793683 TI - Mixed-race couples, residential mobility, and neighborhood poverty. AB - Despite substantial growth in mixed-race coupling, we know little about their association with neighborhood poverty. To address this gap, I utilize data from the Panel Study of Income Dynamics linked to information from four censuses. With these data, I assess the extent to which mixed-race couples are more likely than monoracial couples to migrate in response to higher percentages of neighborhood poverty; and, once they move, I examine the percentage poverty in their destination neighborhoods. I find that most mixed-race couples are similar to white couples in their out-mobility responses to neighborhood poverty. However, when mixed-race couples with black partners migrate they tend to move to neighborhoods with higher poverty concentrations than couples without a black partner. Mixed-race couples without black partners experience similar percentages of poverty in their destination neighborhoods as whites, providing further evidence of the profound impact of black race on residential stratification. PMID- 29793684 TI - From the West Indies to Africa: A universal generational decline in health among blacks in the United States. AB - Research shows that foreign-born blacks have better health profiles than their U.S.-born counterparts. Less is known, however, regarding whether black immigrants' favorable health outcomes persist across generations or whether these patterns differ across the diverse sending regions for black immigrants. In this study, we use data from the 1996-2014 waves of the March Current Population Survey (CPS) to investigate generational differences in self-rated health among blacks with West Indian, Haitian, Latin American, and African ancestry. We show that first-generation black immigrants have a lower probability of reporting fair/poor health than third/higher generation blacks. The health advantage of the first generation over the third/higher generation is slightly more prounced among the foreign-born who migrated to the United States after age 13. Second generation immigrants with two foreign-born parents are generally less likely to report their health as fair/poor than the third/higher generation. However, we find no evidence that self-reported fair/poor health varies between second generation immigrants with mixed nativity parents (only one foreign-born parent) and the third/higher generation. These general patterns hold across each of the ancestral subgroups in the study sample. In summary, our findings highlight a remarkable convergence in health across immigrant generations among blacks in the United States. PMID- 29793685 TI - Trajectories of marijuana use and the transition to adulthood. AB - Alongside the rise of emerging adulthood, policy contexts for marijuana have rapidly changed, with increases in availability and the number of daily users. We identify heterogeneous pathways of marijuana use from age 16 to 26, and examine how these pathways differentiate adult role transitions by age 28. Latent class analyses identified five trajectories: abstainers, dabblers, consistent users, early heavy quitters, and persistent heavy users. Dabblers are no different from abstainers on educational and labor market outcomes, and both have higher odds of adult role transitions relative to heavier use classes. Dabblers differ from abstainers on certain family transitions, yet remain distinct from the heavier use classes. Besides parenthood, early heavy quitters and persistent heavy users are similar, suggesting that heavy use is particularly detrimental early during transitions to adulthood. Distinct trajectories of marijuana use may differentiate young people into divergent pathways of transitions to adulthood, which may have long-term implications. PMID- 29793686 TI - Applying the matching law as micro-foundation of social phenomena. AB - Social phenomena are suggested to be explained by the matching law - an empirical regularity of individual behaviour. While a considerable amount of psychological research on this law exists, only a few sociological applications can be found. This paper points to the problems that come with its usage as micro-foundation of social behaviour and provides solutions. In particular, a model of melioration learning enables the derivation of social phenomena from the matching law. The proposed approach is illustrated by the application of the learning model to the volunteer's dilemma. In contrast to game-theoretical solutions, the matching law leads to more intuitive results in case of the asymmetric dilemma. The relationship between the matching law and utility maximisation is discussed by its integration into economic consumer theory. PMID- 29793687 TI - How to study political activists: A petition survey approach. AB - A major challenge for social movement and political campaign studies is generating large, representative samples of political activists. This paper outlines a strategy of surveying those who participate in a common, baseline form of political action: signing petitions. Similar to protest surveys, signing a petition constitutes a more baseline low cost/low risk form of political activism. In 26 states in the U.S. petition lists are public record and, with modest effort, can be used to study a wide variety of issues, groups and campaigns. We outline the steps and costs involved in such a petition survey and how to improve response rate. To assess response bias, we compare demographic and political affiliation measures acquired from a marketing analytics company (Experian) for respondents and non-respondents to our survey of petition signers for two state-level initiative elections, finding only modest and interpretable response bias. The methods presented here have broader implications for survey research in general. PMID- 29793688 TI - New options for national population surveys: The implications of internet and smartphone coverage. AB - Challenges to survey data collection have increased the costs of social research via face-to-face surveys so much that it may become extremely difficult for social scientists to continue using these methods. A key drawback to less expensive Internet-based alternatives is the threat of biased results from coverage errors in survey data. The rise of Internet-enabled smartphones presents an opportunity to re-examine the issue of Internet coverage for surveys and its implications for coverage bias. Two questions (on Internet access and smartphone ownership) were added to the National Survey of Family Growth (NSFG), a U.S. national probability survey of women and men age 15-44, using a continuous sample design. We examine 16 quarters (4 years) of data, from September 2012 to August 2016. Overall, we estimate that 82.9% of the target NSFG population has Internet access, and 81.6% has a smartphone. Combined, this means that about 90.7% of U.S. residents age 15-44 have Internet access, via either traditional devices or a smartphone. We find some evidence of compensatory coverage when looking at key race/ethnicity and age subgroups. For instance, while Black teens (15-18) have the lowest estimated rate of Internet access (81.9%) and the lowest rate of smartphone usage (72.6%), an estimated 88.0% of this subgroup has some form of Internet access. We also examine the socio-demographic correlates of Internet and smartphone coverage, separately and combined, as indicators of technology access in this population. In addition, we look at the effect of differential coverage on key estimates produced by the NSFG, related to fertility, family formation, and sexual activity. While this does not address nonresponse or measurement biases that may differ for alternative modes, our paper has implications for possible coverage biases that may arise when switching to a Web-based mode of data collection, either for follow-up surveys or to replace the main face-to-face data collection. PMID- 29793689 TI - Corrigendum to "Market transformation and the opportunity structure for gender inequality: A cohort analysis using linked employer-employee data from Slovenia" [Soc. Sci. Res. 67 (2017) 14-33]. PMID- 29793690 TI - Competitive threat and temporal change in anti-immigrant sentiment: Insights from a hierarchical age-period-cohort model. AB - The study focuses on over-time change in anti-immigrant attitudes across European societies and on the role played by cohorts in producing the change in attitudes. We assembled data from four waves of the European Social Surveys for 14 countries between 2002 and 2014. The data analysis is conducted within the framework of a hierarchical age-period-cohort model (HAPC) to estimate the dynamic relations between anti-immigrant sentiment and country's social and economic conditions, while taking into consideration variations across individuals and birth-cohorts. The analysis lends support to expectations derived from the 'competitive threat' theoretical model. The findings show that a higher share of non-European ethnic minorities in the country's population is associated with a higher level of ant immigrant attitudes. Anti-immigrant sentiment was found to be more pronounced in the 'old immigration countries' than in the 'new immigration countries.' The impact of economic conditions on anti-immigrant sentiment becomes evident through the effect of cohort in the 'new immigration countries': cohorts that entered the labor market when the unemployment rate was high are likely to hold more negative attitudes toward immigrants. PMID- 29793691 TI - Is there really such thing as immigrant spatial assimilation in France? Desegregation trends and inequality along ethnoracial lines. AB - This article describes patterns of ethnoracial and socioeconomic neighborhood attainment among North African, sub-Saharan African, and South European immigrants in France. We use French data from Trajectories and Origins to document the effects of assimilation variables such as immigrant generation, age at migration, parental age at migration, mixed ascendance, and socioeconomic status that are rarely available in large scale surveys. A simultaneous equation design is used to show patterns in ethnoracial and socioeconomic desegregation across groups and the contrasting ways in which these outcomes overlap. The findings highlight the weak impact of assimilation variables in accounting for spatial trajectories compared to the predominance of ethnoracial group, and document a higher risk of cumulative spatial disadvantage among North Africans and sub-Saharan Africans. The conclusion discusses the implications of these findings for understanding the ethnoracial dimensions of socio-spatial stratification in France. PMID- 29793692 TI - Partner selection and social capital in the status attainment process. AB - Why is individual success so strongly affected by parental socioeconomic status? We argue that parental socioeconomic status affects the socioeconomic status of one's romantic partner, thereby partially determining one's own social capital and socioeconomic status. Censored-inflated structural equation models using data from the NEtherlands Longitudinal Lifecourse Study (NELLS) and British Household Panel Survey (BHPS) confirm these relationships, while cross-lagged analyses suggest that they may be causal in nature. The strong tendency for people to have a romantic partner that reflects their socioeconomic origin shows how far the influence of the parental home stretches and why it does so. PMID- 29793693 TI - Racial variation in the effect of motherhood on women's employment: Temporary or enduring effect? AB - Part of the motherhood wage penalty results from mothers' loss of work experience, yet little research has investigated whether this loss is temporary or accumulates over time. Using growth curve models and data from the National Longitudinal Study of Youth (1979), I examine the extent to which motherhood reduces work experience over the life course among White, Black, and Hispanic women. Results indicate that motherhood slows the accretion of experience in full time work for all racial-ethnic groups, having an enduring effect on women's employment. The effect is stronger among Whites and mothers with two or more children, remaining sizeable as women approach retirement age. By age 50, White and Hispanic mothers with two or more children exhibit between two to seven fewer years of experience in full-time employment. Among Blacks, only mothers with three or more children experience a significant reduction, averaging five fewer years of experience in full-time work. PMID- 29793694 TI - Trust and contact in diverse neighbourhoods: An interplay of four ethnicity effects. AB - Ethnically diverse neighbourhoods are generally less cohesive. A negative relationship between neighbourhood diversity and social cohesion is, however, neither a necessary nor a sufficient condition to conclude that neighbourhood diversity erodes intra-neighbourhood cohesion. This contribution shows - by using data collected during the second wave of the NEtherlands Longitudinal Lifecourse Study (NELLS) - that: (1) members of ethnic minority groups are more likely to report having contact with and trust their immediate neighbours than natives (ego ethnicity effect); (2) minority group residents are less likely to be contacted and trusted by their neighbours (alter ethnicity effect) and (3) all ethnic groups prefer to mix with coethnics (dyad ethnicity effect). Once we control for these three ethnic composition effects at the ego, alter and dyad-level, neighbourhood ethnic diversity is no longer related to less contact between neighbours. Previously identified negative relationships between neighbourhood diversity and cohesion should therefore be re-evaluated, as they may be the consequence of ethnic composition effects instead of a true neighbourhood diversity effect. PMID- 29793695 TI - Efficacy of fibrin-sealants in reducing biliary leakage following laparoscopic common bile duct exploration. AB - INTRODUCTION: In spite of the acquired experience with laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis management, there is still a risk of biliary leakage of 5% to 15% following choledochotomy closure. We evaluate the usefulness of fibrin-collagen sealants to reduce the incidence of biliary fistula after laparoscopic choledochorrhaphy. METHODS: We report a retrospective analysis of 96 patients undergoing LCBDE from March 2009 to March 2017, whose closure of the bile duct was completed by antegrade stenting and choledochorraphy or by performing a primary suture. The study population was divided into two groups according to whether they received a collagen-fibrin sealant covering the choledochorrhaphy or not, analyzing the incidence of postoperative biliary fistula in each group. RESULTS: Thirty-nine patients (41%) received a fibrin-collagen sponge while the bile duct closure was not covered in the remaining 57 patients (59%). The incidence of biliary fistula was 7.7% (3 patients) in the first group and 14% (8 patients) in the second group (P=.338). In patients who underwent primary choledochorraphy, the fibrin-collagen sealant reduced the incidence of biliary leakage significantly (4.5% vs. 33%, P=.020), which was a protective factor with an odds ratio of 10.5. CONCLUSION: Fibrin collagen sealants may decrease the incidence of biliary fistula in patients who have undergone primary bile duct closure following LCBDE. PMID- 29793696 TI - Recommendation of use of checklists in tibial intramedullary nail removal: Retrospective study of mechanical complications related to nail removal. AB - BACKGROUND: The removal of implants such as intramedullary nails is one of the most common operations in orthopedic surgery. The indications for orthopedic implants removal will always remain a subject of conversation and hardly supported by literature. The aim of this study to report injuries of treatment in tibial nail removal and to determine if there are fracture characteristics, patient demographics, or surgical details that may predict a complication. METHODS: This is a retrospective seven-year (2010-2016) study including a total of 389 tibial intramedullary nail removals at the Helsinki University Hospital's orthopedic unit. Patients with tibial fracture and removal of intramedullary nail were identified from the hospital discharge register and analyzed. RESULTS: A total of 21 (5,4%) nail removal related mechanical complications (iatrogenic fractures, nerve injuries, failures to remove the nail) were noted. The most common complication was iatrogenic fracture (n = 15, 3,8%). In 6/15 cases the fracture was caused by broken interlocking screws, In 5/15 cases the iatrogenic fracture was caused accidentally by extracting the nail without prior removal of all distal interlocking screws. In one case, new condensed bone had formed around the nail's distal end and case the forced nail extraction caused a re-fracture in both tibia and fibula. CONCLUSION: Nail removal can be a challenging operation which does not always receive the necessary preoperative planning or operative expertise. Iatrogenic fractures were most often caused by inadequate preoperative planning or assuming that a broken interlocking screw tilts during the extraction. We suggest the use of checklists in preoperative planning to avoid fractures caused by broken or undetected interlocking screws. PMID- 29793697 TI - Introduction to health services research database papers. PMID- 29793698 TI - Effect of Ultrasound-guided Nerve Block With 0.75% Ropivacaine at the Mid-forearm on the Prevalence of Moderate to Severe Pain After Hand Surgery. AB - PURPOSE: This study tested the hypothesis that ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine reduces the prevalence of moderate to severe pain after wrist and hand surgery, and provides prolonged postoperative analgesia with minimal motor blockade. METHODS: Thirty patients undergoing elective wrist and hand surgery were randomly assigned to 1 of 2 groups: group R (n = 15) and group NS (n = 15). We combined an ultrasound-guided supraclavicular brachial plexus block with mid-forearm median, radial, and ulnar nerve block in all patients. The supraclavicular brachial plexus was blocked with 20 mL of 1.5% lidocaine, and the mid-forearm nerves were blocked with 15 mL of either 0.75% ropivacaine (group R) or normal saline (5 mL each nerve) (group NS). A blinded observer provided a numeric rating pain score at 1, 2, 6, 12, 24, and 48 hours after surgery. The durations of sensory and motor blockade, patient satisfaction, morphine requirement for postoperative pain rescue, and adverse events were recorded. FINDINGS: The prevalence of moderate to severe pain in group R was significantly lower than that in group NS (33% vs 86%; P = 0.008). The highest mean (SD) numeric rating pain score (worst pain) in group R was lower than that in group NS (2.7 [1.9] vs 5.6 [2.9]; P = 0.004), and the median (Q1, Q3) amount of morphine required for postoperative pain rescue in group R was lower than that in group NS (0 [0, 6] vs 8 [6, 10]; P = 0.001]. Additionally, there were no differences in the durations of motor blockade between the 2 groups. IMPLICATIONS: Based on the findings from this study, ultrasound-guided mid forearm nerve block with 0.75% ropivacaine significantly reduces the prevalence of moderate to severe pain after wrist and hand surgery, provides long-term postoperative analgesia, and facilitates the return of motor function in the upper limb. Chinese Clinical Trial Registry identifier: ChiCTR-IOR-15007278 (October 2015). PMID- 29793699 TI - An advanced pharmacy practice experience in academia: More benefit than burden! AB - INTRODUCTION: Within the curriculum, students gain exposure to careers in community, ambulatory, and institutional pharmacy. Students may not consider alternative options, like academia. Perceived barriers to incorporation by faculty may limit opportunities for students. The following commentary describes one student and faculty member's experience with an academic advanced pharmacy practice experience (APPE), and offers suggestions for overcoming potential barriers to implementation. PERSPECTIVE - STUDENT: During my rotation, I learned just how much hard work and dedication goes into teaching. Before this rotation I didn't have a good sense of the responsibilities and requirements of a faculty member. My goals were to participate in as many activities my preceptor could allow me to be a part of. I wanted to get a true idea of what her daily demands were. Because of this rotation, I have a better understanding of the challenges and rewards of a career in academia, and it has solidified my interest in teaching. PERSPECTIVE - FACULTY: I'll admit that taking on an academic APPE student during my busiest term made me think twice. To assure a smooth rotation, I spent a lot of time in the planning phase which allowed the student and I to communicate effectively from day one. Outlining my expectations while ensuring I had a good understanding of my student's objectives for the rotation made sure we had a successful rotation. CONCLUSION: Elective APPEs are the perfect time for students to explore a career in academia. Faculty are well positioned to offer rotations to promote interest in academia that may be mutually beneficial. PMID- 29793700 TI - Perceptions of organizational culture and organizational citizenship by faculty in U.S. colleges and schools of pharmacy. AB - OBJECTIVES: (1) Describe perceptions of organizational culture and prevalence of organizational citizenship behaviors (OCBs) among faculty at United States (U.S.) colleges/schools of pharmacy; (2) determine which aspects of those phenomena are strongest and which are most problematic; (3) evaluate the psychometric properties of measures for organizational culture and OCBs in academic pharmacy; and (4) identify any relationships between organizational culture and organizational citizenship among academic pharmacy faculty. METHODS: A random sample of 600 U.S. academic pharmacists acquired from the American Association of Colleges of Pharmacy were distributed an email survey through the use of Qualtrics technology. The procedures closely resembled the Total Design Method advocated to maximize survey response, including use of a pre-notification letter, reminders, and a nominal financial inducement. In addition to demographic questions, the survey employed multiple-item measures of organizational culture and OCBs described previously in the literature and derived from Delphi consensus building procedures. The analysis plan incorporated use of factor and item analyses to evaluate psychometric properties of the measure and elicit the inherent domains comprising these phenomena, along with descriptive statistics to describe facets of organizational culture and OCBs that were most prevalent. RESULTS: A total of 177 responses were delivered. Factor analysis of organizational culture revealed a five-factor solution emphasizing achievement orientation, professionalism, stability, supportiveness, and reflectiveness. OCB domains were along the possibility of faculty being virtuous, disrespectful, sportsmanlike, and benevolent/malevolent. Even while multi-faceted and avoiding a simple typological descriptor, academic pharmacy cultures were reportedly healthy. Sportsmanship, while still somewhat commonly observed, was seen less frequently than other behaviors. The measures demonstrated logical, cogent factor structures and excellent internal consistency reliability. CONCLUSIONS: Psychometrically well-performing measures were used to assess the multi-faceted organizational culture of academic pharmacy programs and the organizational citizenship behaviors of its constituent faculty. The results can be used to measure these phenomena at individual organizations for benchmarking and to inform future inquiries that can assist with development of strategies that impact academic worklife and outcomes. PMID- 29793701 TI - Determinants of health-related quality of life in international graduate students. AB - INTRODUCTION: International graduate students often experience additional levels of stress due to acculturation. Given the impact of stress on health outcomes (both physical and mental), this study examined the health-related quality of life (HRQoL) in international graduate students to determine its association with acculturative stress, perceived stress, and use of coping mechanisms. METHODS: A cross-sectional, self-administered survey was designed and sent to 38 student chapters within the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) student network. HRQoL [physical component summary (PCS) and mental component summary (MCS)] was measured using the 12-item Short Form (SF-12) while coping mechanisms were assessed using the Brief COPE Scale. Acculturative and perceived stress were assessed using the Acculturative Stress Scale for International students [ASSIS] and Graduate Stress Inventory-Revised (GSI-R), respectively. Demographic and personal information (e.g. age, religion) were also collected. Descriptive statistics (mean +/- SD and frequency) and hierarchical multiple regression analysis were conducted. RESULTS: The average PCS and MCS were 60 +/- 9 and 44 +/- 13, respectively, indicating that while the physical health was above the United States (US) general population norm (50), mental health scores were lower. Findings from the hierarchical multiple regression showed that perceived and acculturative stress significantly predicted mental health. Acculturative stress was also a significant predictor of physical health. CONCLUSION: The results from this study support the hypothesis that international students in the US experience both perceived and acculturative stress that significantly impacts their HRQoL. Universities should consider providing education on stress reduction techniques to improve the health of international graduate students. PMID- 29793702 TI - Overcoming pitfalls: Results from a mandatory peer review process for written examinations. AB - PROBLEM DESCRIPTION: Written assessments are essential components of higher education practices. However, faculty members encounter common pitfalls when designing questions intended to evaluate student-learning outcomes. The objective of this project was to determine the impact of a mandatory examination peer review process on question accuracy, alignment with learning objectives, use of best practices in question design, and language/grammar. QUALITY IMPROVEMENT METHODS: A mandatory peer review process was implemented for all midterm (before phase) and final (after phase) examinations. Peer review occurred by two reviewers and followed a pre-defined guidance document. Non-punitive feedback given to faculty members served as the intervention. Frequencies of flagged questions according to guidance categories were compared between phases. RESULTS OF CQI INQUIRY: A total of 21 midterm and 21 final exam reviews were included in the analysis. A total of 637 questions were reviewed across all midterms and 1003 questions were reviewed across all finals. Few questions were flagged for accuracy and alignment with learning outcomes. The median total proportion of questions flagged for best practices was significantly lower for final exams versus midterm exams (15.8 vs. 6.45%, p = 0.014). The intervention did not influence language and grammar errors (9.68 vs. 10.0% of questions flagged before and after, respectively, p = 0.305). CONCLUSIONS: A non-punitive peer review process for written examinations can overcome pitfalls in exam creation and improve best practices in question writing. The peer-review process had a substantial effect at flagging language/grammar errors but error rate did not differ between midterm and final exams. PMID- 29793703 TI - Factors associated with mentor satisfaction among teaching and learning curriculum program participants. AB - OBJECTIVES: To evaluate participants' satisfaction with their teaching mentor relationship in a teaching and learning curriculum (TLC) and determine characteristics that are associated with high mentee satisfaction. METHODS: A 31 item survey instrument was administered to all 2015-2016 participants of the Teaching Certificate Program. RESULTS: Seventy percent of program participants (n = 60/86) responded to the survey. Overall, 80% of program participants were satisfied or very satisfied with their mentor relationship. Characteristics associated with participants reporting that they were very satisfied with their teaching mentor relationship included mentor availability for face-to-face contact and affiliation with the same institution. Mentor actions associated with high mentee satisfaction included reviewing lecture slides, providing midpoint feedback, providing career advice, and attending mentee lectures. CONCLUSIONS: Teaching certificate program participants perceive increased mentor accessibility and frequent interaction as key factors to a satisfying mentor-mentee relationship. Optimizing and standardizing mentorship programs are essential to the success of postgraduate teaching curriculums. PMID- 29793704 TI - Specialization within pharmacy education: A survey of curricular track or concentration offerings. AB - INTRODUCTION: The purpose of this national survey was to determine what constitutes a curricular track or concentration within colleges and schools of pharmacy. Additionally, for programs not currently offering curricular tracks or concentrations, this survey sought to identify barriers to implementation. METHODS: A survey instrument was developed and piloted. It was distributed electronically via SurveyMonkey to members of the American Association of Colleges of Pharmacy (AACP) Curriculum Special Interest Group (SIG) contact list, along with academic affairs contacts for the balance of programs not included on the SIG contact list, as obtained via a targeted website search. RESULTS: Sixty five of 134 programs responded to the survey (48.5%). Sixteen programs currently offer 38 curricular tracks or concentrations. On average, tracks or concentrations contained 10.6 didactic credits, with 4.6 elective and six required didactic credits; 0.7 introductory pharmacy practice experience (IPPE) credits; and 5.3 advanced pharmacy practice experience (APPE) credits, with 2.8 elective and 2.5 required APPE credits. Most tracks did not require a summative project (n = 13), while some required completion of a project individualized by interest/needs (n = 7). Forty-nine programs do not currently offer curricular tracks, most frequently due to logistics of faculty, oversight, or the curriculum structure. Of these programs not currently offering curricular tracks or concentrations, 38.8% are currently considering implementation. CONCLUSION: Existing tracks or concentrations are highly variable in their composition. Many colleges and schools of pharmacy are considering implementation of curricular tracks or concentrations; this report provides guidance for appropriate rigor and development considerations. PMID- 29793705 TI - Influencing the future of rural-focused pharmacy education: Identifying factors pertinent to pharmacy practice in rural health environments. AB - INTRODUCTION: To identify themes regarding the skills used on a regular basis by pharmacists practicing in rural areas. METHODS: A cross-sectional qualitative survey was administered to pharmacists working in a non-clinical capacity in rural community and hospital practice. Pharmacists were identified in conjunction with departments of experiential education, boards of pharmacy, and other rural health experts. Contacts were interviewed using a semi-structured approach with thematic saturation determining the number of interviews. Themes were identified by reviewing interview notes and transcripts for repeated phrases, concepts, and ideas then compared with the literature. RESULTS: Fifteen pharmacists practicing in rural areas were interviewed. Themes related to practice environment, patient population, skills used by rural pharmacists, preparation of students, and continuing education needs were identified. Many of the identified themes are corroborated by published literature. One pharmacy-specific theme not corroborated was "pharmacy specialization is not helpful". DISCUSSION AND CONCLUSIONS: The results of this study coupled with data from rural medical education may be useful for educators developing rural-focused coursework via reverse design. PMID- 29793707 TI - Knowledge and perceptions toward cardiology pharmacy education and training: Malaysian pharmacy students' perspectives. AB - INTRODUCTION: The role of pharmacists in the patient care process is developing in the Malaysian healthcare setting. Pharmacy students are required to be aware of cardiology pharmacy practice as this is one of the top national disease burdens in Malaysia. This study was conducted to assess the knowledge and perceptions of pharmacy students toward the cardiology pharmacy specialty practice. METHODS: A descriptive cross-sectional study was conducted. The study instrument was a 31-item self-developed questionnaire. The target participants were third and fourth-year pharmacy students in one of the public Malaysian pharmacy schools. RESULTS: The overall response rate was 174/209 students (83.3%); 42 (24.1%) were male and 132 (75.9%) were female. The majority of students possessed a sound knowledge regarding cardiology pharmacy services and roles of the cardiology pharmacist. Nevertheless, important differences were noted between the participants in a few particular areas. These included prior familiarity with the term "cardiology pharmacy" (p = 0.032), limitations to the active participation of pharmacists in the cardiology unit in Malaysia (p = 0.013), and perceptions toward the necessity of a cardiology pharmacist to the Malaysian healthcare system (p = 0.005). CONCLUSIONS: Overall, the pharmacy students in our sample have high knowledge of and positive perceptions toward cardiology pharmacy practice. The majority of students perceived the introduction of cardiology pharmacy as a stand-alone subject in the undergraduate pharmacy curriculum in a positive manner. This study may be considered as a starting point for Malaysian pharmacy schools to consider offering focused clinical learning aligned with both the nation's health priorities and the prospective specialty level of clinical pharmacy practice in the country. PMID- 29793706 TI - Evaluating communication skills after long-term practical training among Japanese pharmacy students. AB - INTRODUCTION: The goal of this study was to assess pharmacy students' satisfaction with long-term practical training programs at hospital and community pharmacies and how these programs benefitted communication skills. METHODS: We asked 83 fifth-year pharmacy students to answer anonymous questionnaires assessing their satisfaction and perceived benefits of practical training and to complete Teramachi's Pharmacist Communication Skill Scale (TePSS-31), a measure of pharmacists' communication skills, after undergoing their practical training periods at hospital and community pharmacies in 2014. RESULTS: Over 90% of students who underwent the practical training were satisfied with their experiences. Furthermore, they reported that practical training institution was helpful for improving their communication skills and gave them sufficient opportunity to interact with consulting patients, engage in role play with pharmacists or peers, and observe interactions between pharmacists and patients. Overall, over 80% of students felt that they had shown improvement in communication skills, indicating that the training was effective. We further reconfirmed that the TePSS-31 has good internal consistency. The total scores on the TePSS-31 after the hospital and community pharmacy training programs did not significantly differ, indicating that the place where the training was received did not influence students' acquisition of communication skills. CONCLUSIONS: Most students were satisfied with the long-term practical training at hospital and community pharmacies, and the training helped improve their communication skills for dealing with patients and coworkers. PMID- 29793708 TI - Integration of transgender care into a pharmacy therapeutics curriculum. AB - BACKGROUND AND PURPOSE: To examine the impact of a lecture on transgender health given during a special populations therapeutics course on third-year (P3) pharmacy students' knowledge and confidence of transgender care. EDUCATIONAL ACTIVITY AND SETTING: A two-hour lecture that included both cultural sensitivity and pharmacotherapy aspects of care for transgender individuals was added to a required two-credit therapeutics series offered at the end of the P3 year of a doctor of pharmacy curriculum. Following the lecture, students completed a 17 item knowledge-based survey and ranked their confidence with each answer on a 5 point scale. Students in the fourth-year (P4) class, who had not been given the lecture, also completed the survey. FINDINGS: Students who attended the lecture had a significantly higher mean knowledge score and mean confidence score than students who did not attend. The P3 class had a mean knowledge score of 72.5% while the mean knowledge score for the P4 class was 63.4% (P < 0.01). The P3's mean confidence score was 76.8% and the P4's mean confidence score was 60.6% (P < 0.01). DISCUSSION: To the authors' knowledge, this is the first report on incorporating the topic of transgender care to a required disease and therapeutics series in a college of pharmacy curriculum. SUMMARY: Students who attended a lecture on care of transgender individuals performed significantly better on a knowledge-based assessment and reported having greater confidence in their answers than students who did not attend the lecture. PMID- 29793709 TI - Utilizing desirable difficulties for sterile compounding training in a skills based laboratory course. AB - BACKGROUND AND PURPOSE: Sterile compounding skills are essential components of a professional pharmacy curriculum. The theory of desirable difficulties has been used to facilitate deeper learning of material in other disciplines, but has not been described in pharmacy sterile compounding instruction. The purpose of this work was to evaluate whether challenges introduced in sterile compounding would act as desirable difficulties and result in greater student confidence in their sterile compounding competency. EDUCATIONAL ACTIVITY AND SETTING: Students in the fourth semester of Pharmacy Skills and Applications, a laboratory-based skills course, were presented with challenges in sterile compounding and were asked to complete a questionnaire rating their confidence and describing their experience. FINDINGS: The majority (92.8%) of students reported that the activity increased their confidence in their sterile compounding skills. Students' open-ended responses suggested that most of the knowledge gained was strategic in nature. DISCUSSION: The results of this activity met the instructors' initial goals by positively impacting students' confidence in their ability to overcome challenges with sterile products compounding. Course instructors may explore additional skills in which to introduce desirable difficulties in order to build student confidence. SUMMARY: Course instructors were pleased with the implementation and results of this desirable difficulties activity and plan to continue its use again in future semesters. Incorporating more real-world challenges throughout the skills-lab course may be beneficial to student learning and confidence. With thoughtful planning, faculty at other institutions can readily incorporate similar activities within their own courses. PMID- 29793710 TI - An evaluation of student performance and perceptions within an integrated pharmaceutics course sequence. AB - BACKGROUND AND PURPOSE: To describe the design of an integrated pharmaceutics course sequence and to assess the sequence by evaluating both student performance and perceptions. EDUCATIONAL ACTIVITY AND SETTING: The non-sterile products portion of a pharmaceutics course sequence was designed to integrate the disciplines of physical pharmacy, dosage forms, pharmacy compounding, and pharmaceutical calculations and to include the respective topics deemed most relevant to doctor of pharmacy curriculum. The appropriate course content was organized in a modular format that began with the general concepts of drug product administration, preparation, stability, and performance and then specifically applied these concepts to a variety of non-sterile dosage forms. FINDINGS: Student performance was assessed through several cumulative exams and lab practicals. Mean performance on these assessments was at a level generally considered to be adequate within the study institution. However, students performed better on the assessments having a lesser emphasis on physical pharmacy (p < 0.05) and a greater focus on basic skill development (p < 0.05). Student perceptions were evaluated using a survey instrument that had a useable response rate of 93%. Each course design element was utilized by a majority of respondents and was generally perceived as being beneficial to student learning. SUMMARY: The collected data indicate that the integrated course design facilitated the learning of applicable pharmaceutics-related topics and support the use of a number of different design elements. In addition, this study provides valuable insights for others providing professional-level pharmaceutics-related education and has helped guide our own course improvement efforts. PMID- 29793711 TI - Design and evaluation of a two-phase learner-centered new student orientation program. AB - BACKGROUND AND PURPOSE: To identify student perceptions associated with a learner centered, multi-stage, flipped, new student orientation for a doctor of pharmacy (PharmD) program. EDUCATIONAL ACTIVITY AND SETTING: First-year PharmD students over three years (2012-2014) were engaged in a two-phase learner-centered orientation process designed to allow students to customize the transition experience. After orientation, students completed a survey to assess programming and their perceptions of readiness to begin the PharmD program. Utilizing student feedback, the orientation program evolved each year to better meet the needs of incoming students. FINDINGS: In 2014, 78.9% of students felt confident in their ability to transition to the PharmD program after orientation, an increase from 55.7% in 2012 when the changes in orientation were first implemented. Additionally, student perceptions of readiness to transition to the PharmD program improved each year. DISCUSSION AND SUMMARY: Implementation of a learner centered, flipped, new student orientation may improve students' perceptions of readiness for study and decrease anxiety of transitioning to a PharmD program. Additionally, it may be an effective tool for increasing orientation program efficiency, while improving student engagement. PMID- 29793712 TI - Student agreement regarding adequacy of didactic content and practical experiences of vaccination clinic business operations. AB - BACKGROUND AND PURPOSE: To report student perceived adequacy regarding didactic content and practical experiences of vaccination clinic business operations. EDUCATIONAL ACTIVITY AND SETTING: Didactic content, a case study, and practical experiences regarding vaccination clinic business operations were implemented in related lectures of a Pharmacy Business and Entrepreneurship (PBE) elective and the college of pharmacy sponsored vaccination clinics. An online survey was used to evaluate student perceived adequacy of didactic content and practical experiences of vaccination clinic business operations. FINDINGS: Mean scaled agreement was compared between students in the PBE elective versus those not in the elective. Student confidence in performing business operations was also assessed. Students in the PBE had higher mean confidence than non-elective students regarding staff management (3.23 vs. 2.73, p = 0.04). SUMMARY: Success of the interventions may be attributed to students in the PBE elective that reported a higher mean perceived adequacy of content and practical experiences and confidence in performing nearly all business operations. Still, further evaluation of interventions is being considered to assess effectiveness of learning. PMID- 29793713 TI - The development and impact of active learning strategies on self-confidence in a newly designed first-year self-care pharmacy course - outcomes and experiences. AB - BACKGROUND AND PURPOSE: The primary objective of this investigation was to determine the effectiveness of different active learning exercises in a newly designed flipped-classroom self-care course in applying newly acquired knowledge of self-care and improving the confidence of first-year pharmacy students to recommend self-care treatments and counsel patients. The early development of these skills is essential for the subsequent Community Introductory Pharmacy Practice Experience (CIPPE). EDUCATIONAL ACTIVITY AND SETTING: An unpaired anonymous survey was administered to students, pre- and post-course, to ascertain their opinions on the effectiveness of various teaching strategies and active learning exercises on learning and on their confidence in treatment-planning and patient counseling for self-care patients. Comparison between pre- and post course Likert scores was conducted using a one-way ANOVA followed by a post-hoc Tukey's test with significance at p = 0.05. All other tests of significance were conducted using a student's t-test with significance at p = 0.05. FINDINGS: Students' self-confidence in developing treatment plans and in counseling for non prescription drugs and dietary supplements significantly improved from the beginning to the end of this self-care course. The response rate was high in both the pre- (N = 208, 88.1%) and post- (N = 198, 83.9%) course surveys. The positive change in confidence was not reflected in increased performance on the final exam represented by a lower average score than the midterm exam. DISCUSSION AND SUMMARY: Active learning sessions and the flipped classroom approach in this first-year pharmacy self-care course contributed to increased self-confidence in making recommendations and counseling patients on proper use of nonprescription medications and dietary supplements. PMID- 29793714 TI - Description and assessment of a pilot interprofessional education case competition activity. AB - BACKGROUND AND PURPOSE: A case competition involving pharmacy and nursing students was designed as a pilot project to determine if this would be an effective way to implement interprofessional education (IPE) within the College of Health and Pharmaceutical Sciences at the University of Louisiana at Monroe. EDUCATIONAL ACTIVITY AND SETTING: Level 5 nursing students and third-year pharmacy students were invited to participate in a patient case competition activity as interprofessional teams. A modified version of the Interprofessional Education Collaborative (IPEC) Competency Survey and the Readiness for Interprofessional Learning Scale (RIPLS) Questionnaire were administered before and after the activity. FINDINGS AND DISCUSSION: Nineteen students (nine nursing, 10 pharmacy) participated in the case competition and completed both the pre- and post-survey. Responses to questions in the IPEC Competency Self-Assessment Tool suggest improved self-reported competence in the interaction and values/ethics domains. SUMMARY: Participation in this IPE case competition demonstrated improved engagement with other healthcare professional students as assessed by the IPEC Competency Survey and the RIPLS Questionnaire. This activity could serve as a way for other schools of pharmacy to implement IPE in their curriculum. PMID- 29793716 TI - Students' perceptions of a blended learning pharmacy seminar course in a Caribbean school of pharmacy. AB - BACKGROUND AND PURPOSE: Blended learning (BL) integrates face-to-face and online instructional methods, with applications in pharmacy education. This study aimed to assess pharmacy students' perceptions of BL in a pharmacy seminar course at The University of the West Indies, St. Augustine campus, Trinidad and Tobago. EDUCATIONAL ACTIVITY AND SETTING: Topics based on the use of medicines and public health were presented by student groups during live seminars, supplemented with online activities. An online survey of students' perceptions was administered at the end of the course. The usefulness of learning resources and course activities were assessed using 5-point Likert-like scales (1 = not helpful to 5 = very helpful). The effectiveness of the instructor, blended delivery, time value, and development of critical-thinking were rated on a 5-point Likert scale for agreement (1 = strongly disagree to 5 = strongly agree). Topics that were most instructive and additional topics of interest were also identified. FINDINGS: Approximately 51% of students (37/72) completed the questionnaire; 73% were female and mean age was 24 years. The learning resources and most course activities were generally helpful (median = 4) in facilitating learning. There was strong agreement (median = 5) on the ease of navigating the online platform, and instructor encouraging interest in pharmacy issues. Students agreed (median = 4) that the course facilitated critical thinking, the BL approach was effective, and the time spent was worthwhile. The most instructive topics included medication errors, antibiotic resistance, and medicines in children and the elderly. SUMMARY: BL in pharmacy seminars is a valuable approach to engage students learning about pharmacy and public health. PMID- 29793715 TI - Evaluation of a mock interview session on residency interview skills. AB - BACKGROUND AND PURPOSE: To evaluate the impact of student pharmacist participation in a mock interview session on confidence level and preparation regarding residency interview skills. EDUCATIONAL ACTIVITY AND SETTING: The study setting was a mock interview session, held in conjunction with student programming at the American College of Clinical Pharmacy (ACCP) Annual Meeting. Prior to the mock interview session, final year student pharmacists seeking residency program placement were asked to complete a pre-session survey assessing confidence level for residency interviews. Each student pharmacist participated in up to three mock interviews. A post-session survey evaluating confidence level was then administered to consenting participants. Following the American Society for Health-System Pharmacists (ASHP) Pharmacy Resident Matching Program (RMP), a post-match electronic survey was sent to study participants to determine their perception of the influence of the mock interview session on achieving successful interactions during residency interviews. FINDINGS: A total of 59 student pharmacists participated in the mock interview session and completed the pre session survey. Participants completing the post-session survey (88%, n = 52) unanimously reported an enhanced confidence in interviewing skills following the session. Thirty responders reported a program match rate of 83%. Approximately 97% (n = 29) of the respondents agreed or strongly agreed that the questions asked during the mock interview session were reflective of questions asked during residency interviews. DISCUSSION: Lessons learned from this mock interview session can be applied to PGY1 residency mock interview sessions held locally, regionally, and nationally. SUMMARY: Students participating in the ACCP Mock Interview Session recognized the importance of the interview component in obtaining a postgraduate year 1 (PGY1) pharmacy residency. PMID- 29793717 TI - Quality assurance processes for standardized patient programs. AB - OUR PROBLEM: As the pharmacy profession evolves to include non-dispensing services and collaborative care, greater emphasis is placed on communication skills building through standardized patient programs. Best practices for assuring the quality of standardized patient (SP) programs, however, remains unclear. The objective of this manuscript is to summarize quality assurance processes for standardized patient programs from health professions education literature. METHODOLOGICAL LITERATURE REVIEW: A search of PubMed and Scopus between 2011 and 2016 was conducted and 22 articles were retained for thematic analysis. Articles were screened for relevance to quality assurance. OUR RECOMMENDATIONS AND THEIR APPLICATIONS: The thematic analysis revealed four themes: (1) enhanced SP training programs, (2) structured feedback to students, (3) statistical measurements to ensure inter-rater reliability, and (4) observation and evaluation of the SP to improve SP performance. Specific methods to assure the quality of an SP program were identified, including training program content and feedback techniques. POTENTIAL IMPACT: Although SP programs varied widely in their implementation, there were several common strategies used to evaluate the consistency of performance, effectiveness of feedback to students, and reliability of grading. Additional research is necessary to establish standards for SP programs across professional healthcare disciplines. PMID- 29793719 TI - Editorial. PMID- 29793718 TI - Predicting performance in health professions education programs from admissions information - Comparisons of other health professions with pharmacy. AB - BACKGROUND: The goal of the present review was to assess the state of performance prediction in healthcare programs generally, versus performance prediction in pharmacy schools, using didactic and non-didactic admissions measures. This is important because clinical success represents a combination of skills that are not fully predicted by either type of measure alone. METHODS: PubMed searches were conducted focusing on work published from 2000 onwards, since it is during this period that non-didactic admissions measures have come to be incorporated into the applicant evaluation process. Relevant free full text papers available were used. When these papers were not available by direct import into EndNote, we went directly to the journal to try to retrieve the paper. RESULTS: We acknowledge that health professions programs have been successful in recruiting excellent candidates into their schools. However, based on the modest amount of healthcare program performance accounted for by didactic measures, admissions committees should consider expanding their holistic evaluation of applicants. Schools would benefit from using two-step screening phases in the application process - perhaps evaluating didactic potential in phase 1 and experiential in phase 2. Using combination measures throughout the admission process should help ensure admission of students more likely to be successful throughout their healthcare practice. IMPLICATIONS: Future investigations of the prediction of healthcare program performance by formal combinations of didactic and non didactic admissions measures are imperative. In addition, it is likely that combination admission measures will incorporate more metrics of critical thinking than do simpler approaches. Furthermore, systematic evaluation of the usefulness of the two-step screening approaches to admissions used by most competitive health professions programs also needs to be done. PMID- 29793720 TI - Histogram analysis of apparent diffusion coefficient from whole-body diffusion weighted MRI to predict early response to chemotherapy in patients with metastatic colorectal cancer: preliminary results. AB - AIM: To evaluate apparent diffusion coefficient (ADC) histogram analysis parameters, acquired from whole-body diffusion-weighted magnetic resonance imaging (DW-MRI), as very early predictors of response to chemotherapy in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: This was a single-institution prospective study, approved by the West Midlands-South Birmingham research ethics committee. All patients gave fully informed consent prior to imaging. Sixteen patients with histologically confirmed mCRC were enrolled to the study and 11 were successfully scanned with whole-body DW-MRI before (baseline) and 10.8+/-2.7 days after commencing chemotherapy (follow-up). Therapy response was assessed by RECIST 1.1. Mean ADC and histogram parameters (skewness, kurtosis, 25th, 50th, and 75th percentiles) were compared between progressors and non-progressors at baseline and follow-up. Receiver operating characteristics (ROC) analysis was performed for the statistically significant parameters. Data from metastases were also compared to normative tissue data acquired from healthy volunteers. RESULTS: Three patients had progressive disease (progressors) and eight had partial response/stable disease (non-progressors). Mean, 25th, 50th, and 75th percentiles were significantly lower for progressors at baseline (p=0.012, 0.012, 0.012 and 0.025 respectively) with areas under the ROC curves (AUC)=0.58, 0.50, 0.58 and 0.63, respectively. Skewness and kurtosis were significantly lower for non-progressors at follow-up (p=0.001 and 0.003 respectively) with AUC=0.67 and 0.79 respectively. CONCLUSION: ADC histogram analysis shows potential in discriminating progressive from non-progressive disease in patients with mCRC, who underwent whole-body DW-MRI. The technique can potentially be tested as a response assessment methodology in larger trials. PMID- 29793721 TI - Uric acid versus non-uric acid urinary stones: differentiation with single energy CT texture analysis. AB - AIM: To evaluate the accuracy of computed tomography (CT) texture analysis (TA) to differentiate uric acid (UA) stones from non-UA stones on unenhanced CT in patients with urinary calculi with ex vivo Fourier transform infrared spectroscopy (FTIR) as the reference standard. MATERIALS AND METHODS: Fourteen patients with 18 UA stones and 31 patients with 32 non-UA stones were included. All the patients had preoperative CT evaluation and subsequent surgical removal of the stones. CTTA was performed on CT images using commercially available research software. Each texture feature was evaluated using the non-parametric Mann-Whitney test. Receiver operating characteristic (ROC) curves were created and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different. The features were used to train support vector machine (SVM) classifiers. Diagnostic accuracy was evaluated. RESULTS: Compared to non-UA stones, UA stones had significantly lower mean, standard deviation and mean of positive pixels but higher kurtosis (p<0.001) on both unfiltered and filtered texture scales. There were no significant differences in entropy or skewness between UA and non-UA stones. The average SVM accuracy of texture features for differentiating UA from non-UA stones ranged from 88% to 92% (after 10-fold cross validation). A model incorporating standard deviation, skewness, and kurtosis from unfiltered texture scale images resulted in an AUC of 0.965+/ 00.029 with a sensitivity of 94.4% and specificity of 93.7%. CONCLUSION: CTTA can be used to accurately differentiate UA stones from non-UA stones in vivo using unenhanced CT images. PMID- 29793722 TI - Understanding and Treating Chiari-like Malformation and Syringomyelia in Dogs. AB - Chiari-like malformation (CM) and syringomyelia (SM) are common and debilitating conditions in toy and small breed dogs. CM, considered ubiquitous in the cavalier King Charles spaniel (CKCS) population, results in abnormal cerebrospinal fluid dynamics which can lead to the development of SM. The clinical signs associated with CM/SM are frequently confused with other otologic and dermatologic conditions, which may delay appropriate treatment. A definitive diagnosis of CM/SM requires advanced imaging; however, due to expense associated with this, many cases are managed presumptively and symptomatically for the condition. The primary goal of treatment is to manage neuropathic pain and neurologic deficits through pharmaceutical or surgical approaches. Current literature suggests that most CM/SM-affected dogs have progression of their clinical signs in spite of medical or surgical management; however, most maintain a good quality of life based on owner assessments. Lack of correlation between structural markers of disease and clinician and owner-derived measures of neuropathic pain highlight the need for more robust, quantitative measures of pain in this common veterinary disease. PMID- 29793723 TI - Whelping and Dystocia: Maximizing Success of Medical Management. AB - Dystocia can be defined broadly as "difficult birth" or more specifically as difficulty in the bitch expelling the pups through the cervix, vagina, and vestibule. It is a fairly common emergency presented to the small animal practitioner with an incidence rate of approximately 5%. The incidence of dystocia is highest in toy and brachycephalic breeds, and occurs frequently in small litters (<3 pups) due to fetal oversize and delayed onset of labor. As duration of labor progresses, the mortality of the pups and even the bitch increases, with the highest number of stillborn pups occurring after 6 hours from the time of active parturition. Practitioners should understand the mechanism of normal parturition so that abnormalities can be readily identified and medical or surgical intervention performed in a safe and timely manner. PMID- 29793724 TI - A Review: Emergency Management of Dogs With Suspected Epileptic Seizures. AB - Dogs with seizure disorders are commonly presented to the general practitioner for initial evaluation. The most common diagnosis provided is idiopathic epilepsy. As witnessing seizures is often traumatic for owners, it is important for the practitioner to understand seizure classification, know when to initiate antiepileptic drug therapy and be comfortable with client education regarding seizures. This review briefly discusses the most up-to-date classification of seizures, the necessity to obtain accurate histories and complete examinations, base-line diagnostics to perform, the importance of owner education, and when to start medications. This is not intended to discuss detailed differential lists, in-depth information on antiepileptic drug therapy, long-term management of epileptics or those refractory to their current treatment. PMID- 29793725 TI - Bioelectric Dressing Supports Complex Wound Healing in Small Animal Patients. AB - It is well documented that physiological electric fields provide the earliest signals necessary to initiate cell proliferation, migration, and ultimately reepithelialization of wounds. Additionally, electricity is known to exert an antimicrobial effect. An electric field-generating wound dressing designed to mimic physiological electric fields has not been described in the small animal clinic. This article retrospectively reviews the use of a microcell battery impregnated bioelectric dressing (BED) in 5 small animal patients with complex wounds. For each patient, product application and wound healing progress was monitored and documented over several weeks. Despite the severity of the wounds and being at high risk for infection, all presenting wounds treated with BED achieved complete closure within 4 weeks without becoming infected or requiring grafting. These cases provide early evidence that the use of the BED is feasible in a small animal clinic and may support healing while providing topical, nonantibiotic activity against wound pathogens. PMID- 29793727 TI - Does the environment influence multiple sclerosis pathogenesis via UVB light and/or induction of vitamin D? AB - Multiple sclerosis (MS) is a disease of presumed auto-immune origin. Long standing observations such as the correlation between MS incidence and geographical latitude or the levels of Vitamin D (Vit D) in the serum have implicated the environmental factors UVB radiation and diet in the etiology of the disease. Clinical trials have been conducted and are currently underway to elucidate whether a Vit D enriched diet or treatment with UVB can influence MS incidence, -severity, and -progression, as well as the ideal time point for treatment. This review summarizes the current scientific knowledge to the environmental factors UVB-light and Vit D concerning the clinical aspects of MS in epidemiological studies and clinical trials. PMID- 29793726 TI - Canine Diabetes Mellitus Associated Ocular Disease. AB - Diabetes mellitus (DM) is a commonly encountered disease in companion animal veterinary practice. Ocular complications in dogs with DM are thought to be common but there are no reports of the overall incidence of DM-associated ocular disease. Some complications, such as cataracts and ocular surface disease, can lead to vision loss and significant morbidity among DM patients, therefore early recognition and intervention are essential for successful outcomes. The purpose of this article is to provide a review of several currently known or suspected ocular diseases associated with DM. PMID- 29793729 TI - The European perspective: Coronary artery calcification in South Asians. PMID- 29793728 TI - Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year. AB - In this prospective evaluation of serum and CSF samples, all but two CSF GFAPalpha-IgG positive patients had autoimmune meningoencephalomyelitis while serum GFAPalpha-IgG positivity alone was less specific. Phenotypes were diverse among patients that were serum positive only. Adult and pediatric clinical presentations were similar. Most patients were immunotherapy responsive. Co existing NMDA-R-IgG and cancer were associated with lack of response to first line immunotherapy. Among patients with follow-up information, 18% had relapses. This study demonstrates CSF GFAPalpha-IgG is a specific autoimmune meningoencephalomyelitis biomarker, with favorable corticosteroid response. Lack of response should prompt evaluation for co-existing NMDA-R-IgG or malignancy. PMID- 29793731 TI - Physiological responses to variations in grazing and light conditions in native and invasive fucoids. AB - Poor physiological acclimatization to climate change has led to shifts in the distributional ranges of various species and to biodiversity loss. However, evidence also suggests the relevance of non-climatic physical factors, such as light, and biotic factors, which may act in interactive or additive way. We used a mechanistic approach to evaluate the ecophysiological responses of four seaweed species (three dominant intertidal fucoids, Fucus serratus, Ascophyllum nodosum, Bifurcaria bifurcata, and the invasive Sargassum muticum) to different conditions of grazing, light irradiance and ultraviolet (UV) radiation. We performed a large scale mesocosm experiment with a total of 800 individual thalli of macroalgae. The factorial experimental design included major algal traits, photoacclimation, nutrient stoichiometry and chemical defence as response variables. Few significant effects of the factors acting alone or in combination were observed, suggesting a good capacity for acclimatization in all four species. The significant effects were generally additive and there were no potentially deleterious synergistic effects between factors. Fucus serratus, a species currently undergoing a drastic contraction of its southern distribution limit in Europe, was the most strongly affected species, showing overall lower photosynthetic efficiency than the other species. The growth rate of F. serratus decreased when UV radiation was filtered out, but only in the presence of grazers. Moreover, more individuals of this species tended to reach maturity in the absence of grazers, and the nitrogen content of tissues decreased under full spectrum light. Only the phlorotannin content of tissues of B. bifurcata and of exudates of A. nodosum, both slow-growing species, were positively affected by respectively removal of UVB radiation and the presence of grazers. The findings for S. muticum, a well-established invasive seaweed across European coasts, suggested similar physiological response of this fast-growing species to different levels of grazing activity and light quality/intensity. As expected, this species grew faster than the other species. Bifurcaria bifurcata and A. nodosum only showed minor effects of light quality and grazing on phlorotannins content, which suggests good resistance of these two long-lived species to the experimental conditions. Mechanistic approaches that are designed to analyse interactive effects of physical and biotic factors provide an understanding of physiological responses of species and help to improve the confidence of predictive distribution models. PMID- 29793730 TI - Middle-term follow-up results of Pipkin type IV femoral head fracture patients treated by reconstruction plate and bioabsorbable screws. AB - PURPOSE: To investigate the mid-term curative effects of the treatment of Pipkin type IV femoral head fractures using a reconstruction plate and bioabsorbable screws and provide the evidence for clinical practice. METHODS: From February 2010 to September 2014, 21 patients with Pipkin type IV femoral head fractures were treated surgically. There were 13 males and 8 females with an average age of 41.1 years (range, 20-65 years). The causes of the fractures included traffic accidents (13 cases), falls from a height (four cases), heavy lifting injuries (three cases), and sport injury (one case). All patients were followed up with radiography and three-dimensional reconstruction computed tomography and other checks and any complications were actively managed. Closed reduction of fracture dislocation of the hip was attempted under general anesthesia using the Kocher Langenbeck approach. Femoral head fractures were treated with internal fixation or excision based on the size of the fracture fragments, whereas acetabular fractures were fixed with a reconstruction plate and screws following anatomic reduction. RESULTS: The incisions healed by primary intention in all patients after surgery, without any infection, deep venous thrombosis, or other complications. All 21 patients were followed up for 36-76 months, with an average follow-up duration of 49 months. Postoperative imaging data showed that all dislocations and fractures were anatomically reduced, and bony union of the fractures was achieved. Heterotopic ossification was found in four patients, post traumatic osteoarthritis in three, and avascular necrosis of the femoral head in two. At the final follow-up, the assessment of hip joint function according to the Thompson-Epstein scoring scale was excellent in 10 cases, good in six cases, fair in three cases, and poor in two cases. The rate of excellent and good functional outcomes was 76.1%. CONCLUSION: The mid-term curative effects of a reconstruction plate and bioabsorbable screws in the treatment of Pipkin type IV femoral head fractures is significant, and such the treatment can significantly improve the patient's joint function and quality of life. PMID- 29793733 TI - Corrigendum to "Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans" [J. Mol. Cell. Cardiol. 97 (2016) 93-105]. PMID- 29793732 TI - Successful Midterm Management With an Herbal Decoction, Modified-Goshajinkigan (mGJG) for Non-Proliferative Diabetic Retinopathy: A Case Study. AB - Diabetic retinopathy (DR) is one of the leading cause of blindness worldwide and the most common cause of blindness among the working population. Early treatment of the disease is essential to prevent severe visual loss among patients. But there are few therapeutic options available for early stage diabetic retinopathy. We present the case of an early stage diabetic retinopathy patient presented with retinal hemorrhages in the superior temporal area and disc hemorrhages of disc nasal area. The patient was diagnosed with mild NPDR on fundus examinations. After 6 months of taking modified-Goshaiinkigan (mGJG), the characteristic features of mild NPDR disappeared. Throughout three consecutive years of follow ups, no evident lesions that could be diagnosed as DR were found during fundus examinations. Many components of mGJG have potential efficacy toward diabetic retinopathy. This study suggests that mGJG is a possible medication for early stage DR. Concerning the degenerative characteristics of DR, early management strategies are important in young DM patients and integrative care, such as in this case, are worth investigating further. PMID- 29793734 TI - Management and Rehabilitation of Joint Disease in Sport Horses. AB - Joint disease is one of the most common issues effecting sport horses. Because there is no cure for joint disease, treatment goals surround slowing progression of the disease, minimizing pain, increasing function, and optimizing performance. Accomplishing these goals often requires a multimodal approach that combines systemic medications or supplements; intra-articular therapies, such as corticosteroids or biologics; management considerations; and physical therapy exercises. PMID- 29793735 TI - Upper Airway Conditions Affecting the Equine Athlete. AB - Many abnormalities of the upper airway that can inhibit performance are determined on a critical resting endoscopic evaluation. Some dynamic abnormalities can only be seen during an exercising endoscopic evaluation, which should be performed whenever the history of abnormal noise or performance limitations is not completely consistent with the resting endoscopic findings. Head and neck position may play a critical role in the evaluation process and the exact position during performance should be reproduced during the clinical examination to definitively define the abnormality. Treatments and prognoses are presented. PMID- 29793737 TI - Fractional order PID for tracking control of a parallel robotic manipulator type delta. AB - This paper presents the tracking control for a robotic manipulator type delta employing fractional order PID controllers with computed torque control strategy. It is contrasted with an integer order PID controller with computed torque control strategy. The mechanical structure, kinematics and dynamic models of the delta robot are descripted. A SOLIDWORKS/MSC-ADAMS/MATLAB cosimulation model of the delta robot is built and employed for the stages of identification, design, and validation of control strategies. Identification of the dynamic model of the robot is performed using the least squares algorithm. A linearized model of the robotic system is obtained employing the computed torque control strategy resulting in a decoupled double integrating system. From the linearized model of the delta robot, fractional order PID and integer order PID controllers are designed, analyzing the dynamical behavior for many evaluation trajectories. Controllers robustness is evaluated against external disturbances employing performance indexes for the joint and spatial error, applied torque in the joints and trajectory tracking. Results show that fractional order PID with the computed torque control strategy has a robust performance and active disturbance rejection when it is applied to parallel robotic manipulators on tracking tasks. PMID- 29793738 TI - Hinfinity observer-based event-triggered sliding mode control for a class of discrete-time nonlinear networked systems with quantizations. AB - This paper investigates the problem of Hinfinity observer-based event-triggered sliding mode control (SMC) for a class of uncertain discrete-time Lipschitz nonlinear networked systems with quantizations occurring in both input and output channels. The event-triggered strategy is used to save the limited network bandwidth. Then, based on the zero-order-hold (ZOH) measurement, a state observer is designed to reconstruct the system state, which facilitates the design of the discrete-time sliding surface. Considering the effects of quantizations, networked-induced constraints and event-triggered scheme, the nonlinear state error dynamics and sliding mode dynamics are converted into a unified linear parameter varying (LPV) time-delay system with the aid of a reformulated Lipschitz property. By using the Lyapunov-Krasovskii functional and free weighting matrix, a new sufficient condition is derived to guarantee the robust asymptotic stability of the resulting closed-loop system with prescribed Hinfinity performance. And then the observer gain, event-triggering parameter and sliding mode parameter are co-designed. Furthermore, a novel SMC law is synthesized to force the trajectories of the observer system onto a pre-specified sliding mode region in a finite time. Finally, a single-link flexible joint robot example is utilized to demonstrate the effectiveness of the proposed method. PMID- 29793736 TI - Tobacco Dependence Predicts Higher Lung Cancer and Mortality Rates and Lower Rates of Smoking Cessation in the National Lung Screening Trial. AB - BACKGROUND: Incorporating tobacco treatment within lung cancer screening programs has the potential to influence cessation in high-risk smokers. We aimed to better understand the characteristics of smokers within a screening cohort, correlate those variables with downstream outcomes, and identify predictors of continued smoking. METHODS: This study is a secondary analysis of the National Lung Screening Trial randomized clinical study. Tobacco dependence was evaluated by using the Fagerstrom Test for Nicotine Dependence, the Heaviness of Smoking Index, and time to first cigarette (TTFC); descriptive statistics were performed. Clinical outcomes (smoking cessation, lung cancer, and mortality) were assessed with descriptive statistics and chi2 tests stratified according to nicotine dependence. Logistic and Cox regression models were used to study the influence of dependence on smoking cessation and mortality, respectively. RESULTS: Patients with high dependence scores were less likely to quit smoking compared with low dependence smokers (TTFC OR, 0.50 [95% CI, 0.42-0.60]). Indicators of high dependence, as measured according to all three metrics, were associated with worsening clinical outcomes. TTFC showed that patients who smoked within 5 min of waking (indicating higher dependence) had higher rates of lung cancer (2.07% for > 60 min after waking vs 5.92% <= 5 min after waking; hazard ratio [HR], 2.56 [95% CI, 1.49-4.41]), all-cause mortality (5.38% for > 60 min vs 11.21% <= 5 min; HR, 2.19 [95% CI, 1.55-3.09]), and lung cancer-specific mortality (0.55% for > 60 min vs 2.92% for <= 5 min; HR, 4.46 [95% CI, 1.63-12.21]). CONCLUSIONS: Using TTFC, a one-question assessment of tobacco dependence, at the time of lung cancer screening has implications for personalizing tobacco treatment and improving risk assessment. PMID- 29793740 TI - Commentary on "Extraordinary daytime only urinary frequency in childhood: Prevalence, diagnosis, and management". PMID- 29793739 TI - A needs analysis and guide for interpretation of voiding cystourethrogram for trainees. PMID- 29793741 TI - Featuring: Comparative effectiveness of a pilot patient-centered ultrasound report in the management of hydronephrosis. PMID- 29793742 TI - Featuring: Ultrasound guided ureteroscopy in children: Safety and success. PMID- 29793743 TI - Featuring: Implications of fellowship expansion on future pediatric urologist surgical volumes. PMID- 29793744 TI - Featuring: Prospective study of enhanced recovery after surgery protocol in children undergoing reconstructive operations. PMID- 29793745 TI - Editorial. PMID- 29793746 TI - CEVL interactive - "1-Voice": Shared checklist for prenatal urological consultation. PMID- 29793747 TI - Expert opinion: "1 Voice" elements of prenatal urological consultation. PMID- 29793748 TI - NK Cells Mediate a Crucial Graft-versus-Leukemia Effect in Haploidentical-HSCT to Cure High-Risk Acute Leukemia. AB - Natural killer (NK) cells are involved in innate defenses against viruses and tumors. Their function is finely tuned by activating and inhibitory receptors. Among the latter, killer immunoglobulin-like receptors and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to discriminate between normal and aberrant cells, as well as to recognize allogeneic cells, because of their ability to sense HLA polymorphisms. This latter phenomenon plays a key role in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for high-risk acute leukemia patients transplanted from an NK-alloreactive donor. Different haplo-HSCT settings have been developed, either T depleted or T replete - the latter requiring graft-versus-host disease prophylaxis. A novel graft manipulation, based on depletion of alphabeta T cells and B cells, allows infusion of fully mature, including alloreactive, NK cells. The excellent patient clinical outcome underscores the importance of these innate cells in cancer therapy. PMID- 29793749 TI - [COPD, what is the best treatment?] PMID- 29793750 TI - [Failure of screening programmes: Interval cancer]. PMID- 29793753 TI - Letter to the editor. PMID- 29793752 TI - A comparative study of non-native N-acyl l-homoserine lactone analogs in two Pseudomonas aeruginosa quorum sensing receptors that share a common native ligand yet inversely regulate virulence. AB - Certain bacteria can coordinate group behaviors via a chemical communication system known as quorum sensing (QS). Gram-negative bacteria typically use N-acyl l-homoserine lactone (AHL) signals and their cognate intracellular LuxR-type receptors for QS. The opportunistic pathogen Pseudomonas aeruginosa has a relatively complex QS circuit in which two of its LuxR-type receptors, LasR and QscR, are activated by the same natural signal, N-(3-oxo)-dodecanoyl l-homoserine lactone. Intriguingly, once active, LasR activates virulence pathways in P. aeruginosa, while activated QscR can inactivate LasR and thus repress virulence. We have a limited understanding of the structural features of AHLs that engender either agonistic activity in both receptors or receptor-selective activity. Compounds with the latter activity profile could prove especially useful tools to tease out the roles of these two receptors in virulence regulation. A small collection of AHL analogs was assembled and screened in cell-based reporter assays for activity in both LasR and QscR. We identified several structural motifs that bias ligand activation towards each of the two receptors. These findings will inform the development of new synthetic ligands for LasR and QscR with improved potencies and selectivities. PMID- 29793751 TI - Design, synthesis and molecular modeling of new 4-phenylcoumarin derivatives as tubulin polymerization inhibitors targeting MCF-7 breast cancer cells. AB - A new set of 4-phenylcoumarin derivatives was designed and synthesized aiming to introduce new tubulin polymerization inhibitors as anti-breast cancer candidates. All the target compounds were evaluated for their cytotoxic effects against MCF-7 cell line, where compounds 2f, 3a, 3b, 3f, 7a and 7b, showed higher cytotoxic effect (IC50 = 4.3-21.2 MUg/mL) than the reference drug doxorubicin (IC50 = 26.1 MUg/mL), additionally, compounds 1 and 6b exhibited the same potency as doxorubicin (IC50 = 25.2 and 28.0 MUg/mL, respectively). The thiazolidinone derivatives 3a, 3b and 3f with potent and selective anticancer effects towards MCF-7 cells (IC50 = 11.1, 16.7 and 21.2 MUg/mL) were further assessed for tubulin polymerization inhibition effects which showed that the three compounds were potent tubulin polymerization suppressors with IC50 values of 9.37, 2.89 and 6.13 MUM, respectively, compared to the reference drug colchicine (IC50 = 6.93 MUM). The mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cells were determined for compound 3a due to its potent and selective cytotoxic effects in addition to its promising tubulin polymerization inhibition potency. The results revealed that compound 3a induced cell cycle cessation at G2/M phase and accumulation of cells in pre-G1 phase and prevented its mitotic cycle, in addition to its activation of caspase-7 mediating apoptosis of MCF-7 cells. Molecular modeling studies for compounds 3a, 3b and 3f were carried out on tubulin crystallography, the results indicated that the compounds showed binding mode similar to the co-crystalized ligand; colchicine. Moreover, pharmacophore constructed models and docking studies revealed that thiazolidinone, acetamide and coumarin moieties are crucial for the activity. Molecular dynamics (MD) studies were carried out for the three compounds over 100 ps. MD results of compound 3a showed that it reached the stable state after 30 ps which was in agreement with the calculated potential and kinetic energy of compound 3a. PMID- 29793754 TI - Comparison of biliary atresia with and without intracranial hemorrhage. AB - BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH) is a severe complication of biliary atresia (BA). We aimed to compare the clinical data of BA patients with and without ICH. METHODS: Sixty-three BA patients who underwent Kasai portoenterostomy were included in this study. We retrospectively reviewed their clinical records, and compared the ICH and non-ICH groups. RESULTS: ICH occurred in seven patients (11.1%). The patients with ICH were significantly older at the time of Kasai portoenterostomy (median age: 90.0 vs 65.5 days). The hepatobiliary enzyme levels of the patients with ICH were significantly lower in comparison to the patients without ICH (T-Bil 6.7 vs 9.8 mg/dl; AST 95 vs 194 U/L; ALT 44 vs 114 U/L). On the other hand, the coagulation test values of the patients with ICH were significantly higher in comparison to the patients without ICH (PT 50.0 vs 12.4 s; APTT 200.0 vs 36.9 s). Although the survival rates did not differ to a statistically significant extent, persistent neurological sequelae occurred in two patients in the ICH group. CONCLUSIONS: The hepatobiliary enzyme levels of the patients with ICH were significantly lower than those without ICH. However, coagulopathy was found to be significantly more progressive in patients with ICH. LEVELS OF EVIDENCE: Level III. PMID- 29793755 TI - Intelligence test at preschool-age predicts reading difficulty among school-aged very low birth weight infants in Japan. AB - OBJECTIVE: To elucidate whether the results of an intelligence test at preschool age are predictive of reading difficulty (RD) at school age among very low birth weight infants (VLBWI). METHODS: Subjects were 48 Japanese children whose birth weight was <1500 g and who regularly visited a follow-up clinic. All subjects completed the Wechsler Intelligence Scale for Children-III (WISC-III) during the last grade of kindergarten, and four reading tasks during the second to fourth grade of elementary school. All participants had a full-scale intelligence quotient score of 85 or higher. Subjects with a standard deviation reading time score greater than 2.0 in two or more tasks were considered to have RD. We evaluated the associations between each WISC-III score and RD using logistic regression analyses. Furthermore, we performed receiver operating characteristic (ROC) analysis to determine a cutoff WISC-III score predictive of RD. RESULTS: In the mutually-adjusted model, the adjusted odds ratio per 1 score increase of freedom from distractibility (FD) was 0.832 (95% confidence interval: 0.720 0.962). In the ROC analysis, an FD score of <95.5 was chosen as the cutoff value for predicting RD (sensitivity, 0.77; specificity, 0.74). CONCLUSION: The present study indicated that a lower FD score at preschool age, which was associated with deficits in verbal working memory and attention, is a risk factor for RD at school age among Japanese VLBWI. Further investigation is desired to clarify the cognitive deficits underlying RD in Japanese-speaking preterm children, and to establish appropriate interventions for these children. PMID- 29793756 TI - Contribution of patient-advisors during rehabilitation for replantation of digits improves patient-reported functional outcomes: A presentation of concept. AB - Clinical approach to surgical patients has evolved to include previous patients as part of the treating team in the role of "patient-advisors". Knowing that compliance to rehabilitation protocols is significant for a successful functional hand replantation, we set out to quantify functional patient-reported outcomes in individuals enrolled in a Patient-Advisor Program (PAP). We performed a prospective cohort pilot study of all patients admitted for a finger replantation between July 2015 to January 2016. All patients were offered to partake in the PAP, or else they would constitute the control group. Primary endpoints were functional outcomes as reported by patients at 6-8weeks and 4-6months of follow up. Secondary endpoints were patient-reported pain and quality of life questionnaires. In total, 62 patients were admitted for finger replantation in the studied period, in which 50 agreed to participate in the study, including 7 in the patient-advisors group and 43 in the control group. Patients from the patient-advisors group fared better on mean scores of the Disabilities of the Arm, Shoulder and Hand than controls (29.6 vs 34.8 respectively at 4-6months). Improvements in the McGill Pain Questionnaire were also greater in the studied group (19.9 vs 33.3 at 4-6months). Replantation patients benefiting from the PAP demonstrated superior functional outcomes on self-reported questionnaires, which could be explained by a better understanding of rehabilitation protocols and compliance when previous patients are active members of the treating team. PMID- 29793757 TI - Development and assessment of a simple ecological model (TRIPS) for forests contaminated by radiocesium fallout. AB - The management of vast forested zones contaminated by radiocesium (rCs) following the Chernobyl and Fukushima fallout is of great social and economic concern in affected areas and requires appropriate dynamic models as predictive or questioning tools. Generally, the existing radio-ecological models need less fragmented data and more ecological realism in their quantitative description of the rCs cycling processes. The model TRIPS ("Transfer of Radionuclide In Perennial vegetation Systems") developed in this study privileged an integrated approach which makes the best use of mass balance studies and available explicit experimental data for Scots pine stands. A main challenge was the differentiation and calibration of foliar absorption as well as root uptake in order to well represent the rCs biocycling. The general dynamics of rCs partitioning was simulated with a relatively good precision against an independent series of observed values. In our scenario the rCs biological cycling enters a steady-state about 15 years after the atmospheric deposits. At that time, the simulations showed an equivalent contribution of foliage and root uptake to the tree contamination. But the root uptake seems not sufficient to compensate the activity decline in the tree. The initial foliar uptake and subsequent internal transfers were confirmed to have a great possible impact on the phasing of tree contamination. An extra finding concerns the roots system acting as a buffer in the early period. The TRIPS model is particularly useful in cases where site specific integrated datasets are available, but it could also be used with adequate caution to generic sites. This development paves the way for simplification or integration of new modules, as well as for a larger number of other applications for the Chernobyl or Fukushima forests once the appropriate data become available. According to the sensitivity analysis that involves in particular reliable estimates of net foliar uptake as well as root uptake not disconnected from rCs exchange reactions in soil. PMID- 29793758 TI - The IL-33/ST2 pathway, inflammation and atherosclerosis: Trigger and target? AB - The "inflammatory hypothesis" of atherosclerosis postulates that inflammatory cell signalling drives the formation, growth and ultimately the instability of atherosclerotic plaques, setting up the substrate for the thrombotic response that causes myocardial damage or infarction. The recent Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial has been hailed as the first demonstration, ex iuvantibus, of the inflammatory hypothesis. Indeed, interleukin (IL)-1beta inhibition was found to reduce cardiovascular events in patients with previous myocardial infarction and raised high-sensitivity C reactive protein, despite no effects on the lipid profile. These results prompt a dissection of inflammatory mechanisms of atherosclerosis in order to search for specific biomarkers with prognostic value and/or therapeutic targets. Under this respect, the IL-33/suppression of tumorigenesis 2 (ST2) pathway deserves consideration. Indeed, its elements are particularly expressed in the endothelium of arterial vessels, and the interaction between IL-33 and the ST2 receptor blunts the immune response characteristic of atherosclerosis. By contrast, soluble ST2 (sST2) acts as a decoy receptor for IL-33, thus blocking its protective effects. Despite a solid theoretical framework, no definite demonstration of an involvement of the IL-33/ST2 pathway in atherosclerosis has been provided. Therefore, further studies are warranted to verify if elements of the IL-33/ST2 pathway may be proposed as markers of plaque burden and predictors of future cardiovascular events, and to explore the potential clinical benefit of enhanced IL-33/ST2 signalling in atherosclerosis. PMID- 29793759 TI - Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine). AB - The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice. PMID- 29793760 TI - Palliative Care for Patients With Advanced Heart Disease. AB - Over the past 2 decades, the discipline of palliative care has evolved and expanded such that it is now the standard of care for a variety of acute and chronic processes. Although there are recommendations encouraging incorporation of palliative care into the routine management of patients with chronic cardiac processes, such as congestive heart failure, implementation has been challenging, and nowhere more so than in the cardiac surgical population. However, as the boundaries of surgical care have expanded to include progressively more complex cases, increasing attention has been given to the integration of palliative care into their management. In this review article, the authors describe the existing evidence for palliative care team involvement in patients with non-operative and surgical cardiac diseases and examine future directions for growth in this field. PMID- 29793762 TI - Lnc'ing Ca2+, SERCA and cardiac disease. AB - Loss of SERCA function contributes to reduced contractility, Ca2+ overload and arrhythmias in the diseased heart. A long non-coding RNA (ZFAS1) upregulated in cardiac disease is reported to directly inhibit SERCA function. The implications for cardiac disease and the wider roles of SERCA are discussed. PMID- 29793761 TI - Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials. AB - OBJECTIVE: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings. DESIGN: A meta-analysis of randomized trials. SETTING: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care. PARTICIPANTS: Critically ill or surgical adult patients. INTERVENTIONS: Corticosteroids compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered. CONCLUSIONS: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis. PMID- 29793763 TI - Human medial efferent activity elicited by dynamic versus static contralateral noises. AB - The medial olivocochlear reflex (MOCR) modifies cochlear amplifier function to improve encoding of signals in static noise, but conflicting results have been reported regarding how the MOCR responds to dynamic, temporally-complex noises. The current study utilized three MOCR elicitors with identical spectral content but different temporal properties: broadband noise, amplitude-modulated noise, and speech envelope-modulated noise. MOCR activity was assessed using contralateral inhibition of transient-evoked otoacoustic emissions in 27 normal hearing young adults. Elicitors were presented contralaterally at two intensities of 50 and 60 dB SPL. Magnitude and growth of contralateral inhibition with increasing elicitor intensity were compared across the three elicitor types. Results revealed that contralateral inhibition was significantly larger at the elicitor intensity of 60 dB SPL than at 50 dB SPL, but there were no significant differences in the magnitude and growth of inhibition across the three elicitors, contrary to hypothesis. These results suggest that the MOCR responds similarly to both static and dynamic noise. PMID- 29793765 TI - Stepping boundary of external force-controlled perturbations of varying durations: Comparison of experimental data and model simulations. AB - This study investigated the stepping boundary - the force that can be resisted without stepping - for force-controlled perturbations of different durations. Twenty-two healthy young adults (19-37 years old) were instructed to try not to step in response to 86 different force/time combinations of forward waist-pulls. The forces at which 50% of subjects stepped (F50) were identified for each tested perturbation durations. Results showed that F50 decreased hyperbolically when the perturbation's duration increased and converged toward a constant value (about 10%BW) for longer perturbations (over 1500 ms). The effect of perturbation duration was critical for the shortest perturbations (less than 1 s). In parallel, a simple function was proposed to estimate this stepping boundary. Considering the dynamics of a linear inverted pendulum + foot model and simple balance recovery reactions, we could express the maximum pulling force that can be withstood without stepping as a simple function of the perturbation duration. When used with values of the main model parameters determined experimentally, this function replicated adequately the experimental results. This study demonstrates for the first time that perturbation duration has a major influence on the outcomes of compliant perturbations such as force-controlled pulls. The stepping boundary corresponds to a constant perturbation force-duration product and is largely explained by only two parameters: the reaction time and the displacement of the center of pressure within the functional base of support. Future work should investigate pathological populations and additional parameters characterizing the perturbation time-profile such as the time derivative of the perturbation. PMID- 29793764 TI - Animal model studies yield translational solutions for cochlear drug delivery. AB - The field of hearing and deafness research is about to enter an era where new cochlear drug delivery methodologies will become more innovative and plentiful. The present report provides a representative review of previous studies where efficacious results have been obtained with animal models, primarily rodents, for protection against acute hearing loss such as acoustic trauma due to noise overexposure, antibiotic use and cancer chemotherapies. These approaches were initiated using systemic injections or oral administrations of otoprotectants. Now, exciting new options for local drug delivery, which opens up the possibilities for utilization of novel otoprotective drugs or compounds that might not be suitable for systemic use, or might interfere with the efficacious actions of chemotherapeutic agents or antibiotics, are being developed. These include interesting use of nanoparticles (with or without magnetic field supplementation), hydrogels, cochlear micropumps, and new transtympanic injectable compounds, sometimes in combination with cochlear implants. PMID- 29793767 TI - Kinematics of knees with osteoarthritis show reduced lateral femoral roll-back and maintain an adducted position. A systematic review of research using medical imaging. AB - BACKGROUND: While several studies describe kinematics of healthy and osteoarthritic knees using the accurate imaging and computer modelling now possible, no systematic review exists to synthesise these data. METHOD: A systematic review extracted quantitative observational, quasi-experimental and experimental studies from PubMed, Scopus, Medline and Web of Science that examined motion of the bony or articular surfaces of the tibiofemoral joint during any functional activity. Studies using surface markers, animals, and in vitro studies were excluded. RESULTS: 352 studies were screened to include 23 studies. Dynamic kinematics were recorded for gait, step-up, kneeling, squat and lunge and quasi-static squat, knee flexion in side-lying or supine leg-press. Kinematics were described using a diverse range of measures including six degrees of freedom kinematics, contact patterns or the projection of the femoral condylar axis above the tibia. Meta-analysis of data was not possible since no three papers recorded the same activity with the same measures. Visual evaluation of data revealed that knees with osteoarthritis maintained a more adducted position and showed less posterior translation of the lateral femoral condylar axis than healthy knees. Variability in activities and in recording measures produced greater variation in kinematics, than did knee osteoarthritis. CONCLUSION: Differences in kinematics between osteoarthritic and healthy knees were observed, however, these differences were more subtle than expected. The synthesis and progress of this research could be facilitated by a consensus on reference systems for axes and kinematic reporting. PMID- 29793766 TI - Biomechanics of the soft-palate in sleep apnea patients with polycystic ovarian syndrome. AB - Highly compliant tissue supporting the pharynx and low muscle tone enhance the possibility of upper airway occlusion in children with obstructive sleep apnea (OSA). The present study describes subject-specific computational modeling of flow-induced velopharyngeal narrowing in a female child with polycystic ovarian syndrome (PCOS) with OSA and a non-OSA control. Anatomically accurate three dimensional geometries of the upper airway and soft-palate were reconstructed for both subjects using magnetic resonance (MR) images. A fluid-structure interaction (FSI) shape registration analysis was performed using subject-specific values of flow rate to iteratively compute the biomechanical properties of the soft-palate. The optimized shear modulus for the control was 38 percent higher than the corresponding value for the OSA patient. The proposed computational FSI model was then employed for planning surgical treatment for the apneic subject. A virtual surgery comprising of a combined adenoidectomy, palatoplasty and genioglossus advancement was performed to estimate the resulting post-operative patterns of airflow and tissue displacement. Maximum flow velocity and velopharyngeal resistance decreased by 80 percent and 66 percent respectively following surgery. Post-operative flow-induced forces on the anterior and posterior faces of the soft-palate were equilibrated and the resulting magnitude of tissue displacement was 63 percent lower compared to the pre-operative case. Results from this pilot study indicate that FSI computational modeling can be employed to characterize the mechanical properties of pharyngeal tissue and evaluate the effectiveness of various upper airway surgeries prior to their application. PMID- 29793768 TI - A laboratory captured "giving way" episode in an individual with chronic ankle instability. AB - This brief report details the first ever instrument-based motion description of an accidental "giving way" episode of the ankle joint incurred by a recreational male athlete (age = 22 years; height = 1.78 m; body mass = 97 kg) with chronic ankle instability whilst he was performing a change of direction task. Five inertial measurement units, as well as a high-speed video camera captured his lower limb kinematics during the performance of a maximum effort Agility T-Test, including his accidental "giving way" episode. This episode was analysed and compared to a previous trial during which no incident occurred. Analysis of the inertial measurement unit data revealed that the "giving way" episode was characterised by plantar flexion of the ankle joint, as well as internal rotation and adduction of the ankle-foot complex, with peak rotational velocities reaching 797 degrees /s, 1088 degrees /s and 1734 degrees /s, respectively. This instrument-based motion description provides a unique insight into the characteristic features of a "giving way" episode experienced by a recreational athlete with chronic ankle instability. These findings could inform the development of rehabilitation programmes and the design of protective equipment for individuals with chronic ankle instability. PMID- 29793769 TI - Report of a man with heterotopic ossification of the legs. AB - Heterotopic ossification is an uncommon disorder that consists of deposition of ectopic bone outside the extraskeletal tissues. In the skin, it can be primary, in association with genetic syndromes, or be secondary to different disorders. The latter include subcutaneous ossification of the legs in chronic venousinsufficiency, an infrequent and unrecognized complication. We report the case of a patient with subcutaneous ossification of both legs secondary to venous insufficiency and review the literature. PMID- 29793770 TI - [The respiratory effects of smoking]. AB - A marked increase in the morbidity and mortality of a large number of broncho pulmonary diseases has been documented in relation to smoking. The influence of tobacco smoking on various respiratory conditions. is discussed: incidence, severity or natural history modification of some respiratory illnesses: obstructive lung diseases (COPD, asthma), lung cancer, bacterial, viral respiratory infections, with the impact of smoking on tuberculosis. Finally, the relationship of tobacco with diffuse interstitial lung disease: protective role of smoking (controversial in sarcoidosis, real in hypersensitivity pneumonitis). The benefits of smoking cessation are described. PMID- 29793771 TI - Genetic, host and environmental factors associated with a high prevalence of Anaplasma marginale. AB - Anaplasma marginale is the most prevalent vector-borne pathogen in the livestock industry in Colombia, causing economic losses of approximately USD 4.2 million per year. The present study reports the seasonal transmission patterns, genetic diversity and phylogeographic traits of A. marginale strains in cattle and buffaloes from Colombian livestock areas. A three-point longitudinal survey was designed to evaluate the above characteristics of farms in the Caribbean and Orinoquia regions. The A. marginale prevalence was evaluated in 1432 cattle blood samples, 152 buffalo blood samples and the hemolymph of 439 ticks using semi nested PCR (sn-PCR) targeting the msp5 gene. The molecular prevalence in cattle and buffaloes was 54.8% and 13.1%, respectively, with higher values during the wet and late wet seasons. Factors such as age and production system were significantly associated with the infection. Rhipicephalus microplus was the only carrier of A. marginale DNA, with an infection rate of 17.2%. On the other hand, the tandem repeat and microsatellite analyses of the msp1alpha gene showed high genetic diversity and new tandem repeats that suggested strain adaptation to different transmission modes. Phylogeographic analysis using the msp4 gene showed a relationship between Colombian isolates and Mexican, Brazilian, Venezuelan, European and Asian isolates, as well as two worldwide haplogroups that were associated with the geographical origin of each isolate. In conclusion, this study shows that A. marginale occurs under enzootic stability in both hosts, with a high prevalence of infection during wet months and in animals dedicated to beef production. The genetic variability analyses suggest that a high strain diversity is associated with multiple selective pressures in the study area, while phylogeographic traits suggest a high genetic similarity between Mexican and South American strains. PMID- 29793772 TI - The development of linguistic prediction: Predictions of sound and meaning in 2- to 5-year-olds. AB - Language processing in adults is facilitated by an expert ability to generate detailed predictions about upcoming words. This may seem like an acquired skill, but some models of language acquisition assume that the ability to predict is a prerequisite for learning. This raises a question: Do children learn to predict, or do they predict to learn? We tested whether children, like adults, can generate expectations about not just the meanings of upcoming words but also their sounds, which would be critical for using prediction to learn about language. In two looking-while-listening experiments, we show that 2-year-olds can generate expectations about meaning based on a determiner (Can you see one...ball/two...ice creams?) but that even children as old as 5 years do not show an adult-like ability to predict the phonology of upcoming words based on a determiner (Can you see a...ball/an...ice cream?). Our results, therefore, suggest that the ability to generate detailed predictions is a late-acquired skill. We argue that prediction might not be the key mechanism driving children's learning, but that the ability to generate accurate semantic predictions may nevertheless have facilitative effects on language development. PMID- 29793773 TI - Can emergency physicians accurately distinguish retinal detachment from posterior vitreous detachment?: A response. PMID- 29793774 TI - Early diffusion-weighted imaging and outcome prediction of comatose survivors after suicidal hanging. AB - PURPOSE: Early outcome prediction after suicidal hanging is challenging in comatose survivors. We analysed the early patterns of brain diffusion-weighted magnetic resonance imaging (DWI) abnormalities in comatose survivors after suicidal hanging. METHODS: After suicidal hanging, 18 comatose survivors were prospectively evaluated from January 2013 to December 2016. DWI was performed within 3 h after hanging in comatose survivors. We evaluated Utstein style variables and analysed abnormal spatial profile of signal intensity on DWI, brain apparent diffusion coefficient (ADC) values, and qualitative DWI scores to predict neurological outcomes. RESULTS: All hanging associated cardiac arrest (CA) patients demonstrated bad neurological outcomes; 80% of non-CA comatose patients experienced good neurological outcomes. In hanging survivors with CA, cortical grey matter structures and deep grey nuclei exhibited profound ADC reductions and high DWI scores within 3 h after hanging, which was associated with diffuse anoxic brain damage with poor cerebral performance categories scores. CA comatose survivors had significantly lower ADC values and higher DWI scores compared to non-CA comatose survivors in the cortex and deep grey nuclei. CONCLUSION: Although the presence of CA is the most important clinical prognosticator in hanging-associated comatose survivors, HSI abnormalities and low ADC values in the cortex and deep grey nuclei on DWI performed within 3 h after hanging are well-correlated with unfavourable outcomes regardless of therapeutic hypothermia. Therefore, early DWI may increase the sensitivity of poor outcome prediction and may be an effective combinatorial screening method when available prognostic variables are not reliable or conclusive. PMID- 29793775 TI - Out-of-body experience in the anterior insular cortex during the intracranial electrodes stimulation in an epileptic child. AB - The authors present a case of an out-of- body experience (OBE) that occurred in a child with intractable epilepsy when stimulating the anterior insular cortex (AIC) by intracranial electrodes. After destroying several sites precisely located at the left AIC by radiofrequency thermocoagulation, the patient's seizures disappeared, and the OBE could not be reproduced when repeatedly stimulating these sites. To our knowledge, it has never been reported that an OBE occurred in the AIC. We analyze the mechanism of an OBE mostly appearing in temporo-parietal junction (TPJ) and propose two perspectives for a possible mechanism involving the AIC causing the OBE. PMID- 29793776 TI - Primary undifferentiated sarcoma of the meninges: A case report and comprehensive review of the literature. AB - BACKGROUND AND IMPORTANCE: Sarcomas make up 1% of all cases of adult cancer, with 5-10% of those classified as undifferentiated pleomorphic sarcomas (UPS/PUS) and 0.1-4.3% primary intracranial sarcomas. Intracranial undifferentiated sarcoma is characterized by an earlier age of onset and generally poorer prognosis compared to extracranial undifferentiated sarcomas. Current therapies involve surgical excision with wide margins and radiotherapy, with minimal data available regarding the efficacy of chemotherapy. CASE DESCRIPTION: A 79-year-old man with a history of remote superficial bladder cancer presented with a large frontal scalp lesion. A biopsy was initially attempted by a dermatologist in the outpatient setting, but a follow-up CT scan revealed a skull-eroding, enhancing soft tissue lesion. Neurosurgical treatment revealed an undifferentiated sarcoma. The patient underwent adjuvant radiation therapy of 59.4 Gy fractionated over 45 days following surgery. Follow-up brain MRIs at 1-, 6-, 9-, 12-, 15-, 21-, and 27 months after surgery have not shown any indications of local recurrence or tumor metastasis. Despite the high propensity that undifferentiated sarcomas have for recurrence and metastasis and the patient's advanced age, this patient remains uniquely disease-free. CONCLUSION: We provide a description of an unusual case and comprehensive literature review of UPS to clarify the hallmarks of the disease, identify the difficulties in diagnosis, and provide a summary of therapies employed in the literature with their corresponding patient outcomes. PMID- 29793777 TI - Posterior fossa crowdedness in idiopathic trigeminal neuralgia: Is it the real perpetrator? PMID- 29793778 TI - Preforming of polydioxanone sheets for orbital wall fractures - A technical note. AB - INTRODUCTION: Polydioxanone (PDS) sheets are commonly used in the treatment of orbital wall fractures. A potential drawback of PDS is that it may be difficult to adapt to the anatomy of the orbital walls. Therefore a study was conceived to test the feasibility of preforming PDS sheets. MATERIAL AND METHODS: PDS sheet material was water-heated and preformed using a template based on a statistical anatomical model. Then the deformed sheet was cooled, stored and compared to the original model to investigate post-deformation changes. RESULTS: PDS sheet material could easily be deformed using a mould. No significant post-cooling shape changes were noticed. CONCLUSIONS: PDS sheet material can be preformed into complex geometric shapes. This could be a benefit in the treatment of orbital wall fractures. PMID- 29793779 TI - Impact of early intravelar veloplasty at six months on mandibular growth in patients with Pierre Robin Sequence. AB - Pierre Robin Sequence (PRS) combines mandible microretrognathia, asynchronism of the pharynx and tongue, glossoptosis and, in some cases, cleft palate. Its principal functional consequences are respiratory and feeding problems during the neonatal period. In this study, we focused on the impact of early closure of the cleft at six months on mandibular growth in patients with PRS. We performed a retrospective study of 15 patients followed for PRS and undergoing surgery performed by the same senior surgeon (HB) at our cleft center between 2005 and 2012. These patients underwent early closure of the cleft (at a mean age of 5.87 months) by intravelar veloplasty, as described by Sommerlad. Only one article with exploitable data analyzing facial and mandibular growth in a cephalometric study of children with PRS has been published. The children in this series, constituting the control group for our study, underwent veloplasty between the ages of 12 and 18 months, often accompanied by labioglossoplasty, and the cephalometric study was carried out between the ages of four and seven years. We compared this control group in which surgery was performed at 12-18 months with our series of children undergoing surgery at six months, in a cephalometric study based on teleradiographic profile measurements performed between the ages of four and seven years. We found that early closure of the cleft soft palate yielded results identical to those for the control group in terms of mandibular growth, without the need for labioglossopexy. Finally, early intravelar veloplasty led to early functional improvement in terms of speech and phonation. PMID- 29793780 TI - Evaluation of the potential efficacy of an ultrasound-guided adductor canal block technique in dog cadavers. AB - OBJECTIVE: To evaluate an ultrasound-guided technique for adductor canal (AC) block by describing the distribution of methylene blue around the AC, popliteal fossa, saphenous, tibial and common fibular nerves in dog cadavers. STUDY DESIGN: Prospective experimental trial. ANIMALS: Ten mixed breed canine cadavers weighing 28.55 +/- 3.94 kg. METHODS: Ultrasound scans of the AC were performed bilaterally in 10 canine cadavers. A high-frequency linear transducer was placed on the long axis of the pectineus muscle and using an in-plane technique, an insulated needle was introduced at a proximal to distal direction into the AC. Methylene blue 0.1% (0.3 mL kg-1) was administered followed by dissection. The presence of dye over the target nerves for >=2 cm was considered successful distribution. Three of 10 cadavers were submitted to computed tomography (CT) and one of them to magnetic resonance (MR) evaluation. RESULTS: Methylene blue reached the AC in 20 (100%) and the popliteal fossa in 17 (85%) pelvic limbs. Staining was successful in the saphenous nerve (4.0 +/- 1.57 cm) in 11 (55%) limbs, tibial nerve (2.65 +/- 0.8 cm) in six (30%) and common fibular nerve (2.7 +/- 0.9 cm) in four (20%). There was no evidence of staining around the motor branches of the femoral nerve. No intraneural or intravascular dye spread was found during dissections. Contrast distribution to the popliteal fossa was observed in three limbs (50%) in CT and in one (50%) MR image. CONCLUSIONS AND CLINICAL RELEVANCE: Although the tibial and common fibular nerves were not stained as often as the saphenous nerve, dye was encountered throughout the popliteal fossa near the nerves. The AC block may be useful for intra and postoperative analgesia in stifle surgery with minimal femoral motor dysfunction. However, further study is required to confirm its efficacy and safety in vivo. PMID- 29793781 TI - Thoracic aortic injury caused by chest tube. PMID- 29793782 TI - Amiodarone induced myxedema coma: Two case reports and literature review. AB - Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes. PMID- 29793783 TI - Letter to the Editor regarding recent Heart and Lung: The Journal of Acute and Critical Care Article "In-hospital outcomes of percutaneous ventricular assist devices versus intra-aortic balloon pumps in non-ischemia related cardiogenic shock" by Ogunbayo et al. PMID- 29793784 TI - An assessment of the quality and content of information on diverticulitis on the internet. AB - AIM: Although commonly the first port of call for medical information, the internet provides unregulated information of variable quality. We aimed to evaluate commonly accessed web-based patient information on diverticulitis using validated and novel scoring systems. METHODS: The top internet search engines (Google/Bing/Yahoo) were queried using the keyword 'diverticulitis.' The first 20 websites from each were graded using the DISCERN and Journal of the American Medical Association (JAMA) benchmark criteria. A novel diverticulitis-specific score was devised and applied. RESULTS: Thirty-six unique websites were identified. The mean total DISCERN score for all websites was 39.92 +/- 12.44 (range = 18-62). No website achieved the maximum DISCERN score of 75. The mean JAMA and diverticulitis scores were 2.5 +/- 1.08 (maximum possible score = 4) and 11.08 +/- 4.17 (19 points possible) respectively. Fourteen (35.9%) and 20 (51.2%) did not provide the date of last update and authorship respectively. Thirty-three (84.6%) mentioned surgery as a treatment option; however, the majority (69.7%) did not describe the surgery or the possibility of a stoma. All except two described disease symptoms. Only ten (25.64%) provided information on when to seek further medical advice or help. CONCLUSION: Web-based information on diverticulitis is of variable content and quality. The majority of top websites describe disease symptoms and aetiology; however, information to prompt seeking medical attention if required, descriptions of surgical procedures and the possibility of stoma creation are poorly described in the majority of websites. These findings should be highlighted to patients utilising the internet to obtain information on diverticulitis. PMID- 29793785 TI - Determinants of physical activity promotion by smoking cessation advisors. AB - OBJECTIVE: To investigate the cross-sectional association between personal physical activity (PA) level, Theory of Planned Behavior (TPB) constructs toward PA promotion, and PA promotion behavior among smoking cessation advisors. METHOD: 149 smoking cessation advisors were invited to complete online questionnaires. Hypotheses were tested using Bayesian path analysis. RESULTS: Attitudes and perceived behavioral control (PBC) of smoking cessation advisors were related to PA promotion intentions; intentions were in turn related to PA promotion behaviors. Advisors' personal PA level was indirectly associated with PA promotion behaviors through PBC and PA promotion intentions. CONCLUSION: The TPB is a relevant theoretical framework with which to explore determinants of PA promotion behavior among smoking cessation advisors. The PA level of health care professionals may be linked to PA promotion behavior through some TPB constructs. PRACTICE IMPLICATIONS: Smoking cessation advisor training should include education on attitude development (e.g., PA benefits on smoking cessation), PBC (e.g., modality of PA prescription) and PA promotion intentions (e.g., goal setting). Smoking cessation advisors should also be encouraged to regularly practice PA in order to improve their PA promotion behaviors. PMID- 29793786 TI - Factors associated with physical activity promotion by allied and other non medical health professionals: A systematic review. AB - OBJECTIVE: To identify factors associated with non-medical health professionals' engagement in physical activity (PA) promotion. METHODS: Five electronic databases were searched for studies including practising health professionals (excluding medical doctors), a PA promotion practice measure, a test of association between potential influencing factors and PA promotion practice, and written in English. Two researchers independently screened studies and extracted data. Extracted data were synthesized in a tabular format with a narrative summary (thematic analysis). RESULTS: Thirty studies involving 7734 non-medical health professionals were included. Self-efficacy in PA promotion, positive beliefs in the benefits of PA, assessing patients' PA, and PA promotion training were the main factors associated with engaging in PA promotion. Lack of remuneration was not associated. Common study limitations included a lack of information on non-responders, data collection by survey only and limited reliability or validity testing of measurements. CONCLUSIONS: There are common factors influencing PA promotion, but the absence of studies from some health professions, limitations related to study measures, and the lack of randomised controlled intervention trials highlights the need for further research. PRACTICE IMPLICATIONS: The factors identified may prove useful for guiding the development of strategies to encourage greater engagement in PA promotion by health professionals. PMID- 29793787 TI - [A spontaneous hyphema]. PMID- 29793788 TI - [Idiopathic sclerochoroidal calcifications associated with asymptomatic polypoidal choroidal vasculopathy, a case report]. PMID- 29793789 TI - Axenfeld-Rieger syndrome. PMID- 29793790 TI - [Retinal arterial occlusion associated with meningoencephalitis in the Behcet disease: Case report]. PMID- 29793792 TI - Dietary signals in the premolar dentition of primates. AB - Dietary adaptations specific to the premolar row remain largely undocumented across primates. This study examines how relative premolar size varies among broad dietary groups (i.e., folivores, frugivores, insectivores, hard-object feeders) using a phylogenetically and ecologically diverse sample of species. We quantified relative premolar size with shape ratios computed using mandibular length, body mass, palate area, and M1 area to evaluate hypotheses that link variation in relative premolar size to differences in tooth loading, energy requirements, the probability of tooth-food-tooth contact during mastication, and shifts in preferred bite point. Our results revealed the following dietary signals. First, primate folivores have large premolar rows relative to palate area in comparison to frugivores and insectivores. This contrast is consistent with the hypothesis that folivores require large postcanine teeth relative to the size of the oral cavity to increase the probability of particle fracture during mastication. Second, hard-object feeders are distinct from other groups in having P4s that are large relative to their M1s. This morphology is not associated with an increase in the size of the premolar row relative to mandibular length. This combination challenges the idea that hard-object feeders have large premolars as an adaptive response to resisting the loads incurred when processing mechanically challenging foods. We therefore interpret the large P4/M1 ratios of hard-object feeders as indicating greater functional integration across the premolar-molar boundary owing to a mesial shift in preferred bite point. Finally, in a restricted subset of anthropoids, we found that, relative to mandibular length, premolar area increases with dietary elastic modulus (E) and toughness (R), indicating that relative premolar size is evolutionarily sensitive to food mechanical properties. Thus, our results show that relative premolar size is correlated with diet, highlighting the importance of this region for understanding the evolutionary history of primate dietary adaptations. PMID- 29793791 TI - Cranial vault thickness variation and inner structural organization in the StW 578 hominin cranium from Jacovec Cavern, South Africa. AB - The Sterkfontein Caves site is one of the richest early hominin fossil localities in Africa. More specifically, the fossiliferous deposits within the lower-lying Jacovec Cavern have yielded valuable hominin remains; prominent among them is the Australopithecus partial cranium StW 578. Due to the fragmentary nature of the braincase, the specimen has not yet been formally assigned to a species. In this context, we employ microtomography to quantify cranial thickness and composition of StW 578 in order to assess its taxonomic affinity. As comparative material, we investigate 10 South African hominin cranial specimens from Sterkfontein (StW 505, Sts 5, Sts 25, Sts 71), Swartkrans (SK 46, SK 48, SK 49) and Makapansgat (MLD 1, MLD 10, MLD 37/38), attributed to either Australopithecus or Paranthropus, as well as 10 extant human and 10 extant chimpanzee crania. Thickness variation in and structural arrangement of the inner and outer cortical tables and the diploe are automatically assessed at regular intervals along one parasagittal and one coronal section. Additionally, topographic cranial vault thickness distribution is visualized using color maps. Comparisons highlight an absolutely and relatively thickened condition of the StW 578 cranial vault versus those of other South African Plio-Pleistocene hominins. Moreover, in StW 578, as well as in the Australopithecus specimens Sts 5 and Sts 71 from Sterkfontein, the diploic layer contributes substantially to cumulative vault thickness (i.e., >60%). Within the comparative sample investigated here, StW 505 and Sts 71 from Sterkfontein Member 4, both attributed to Australopithecus, most closely resemble StW 578 in terms of cranial vault thickness values, tissue proportions, and two- and three-dimensional distributions. Including additional Plio-Pleistocene Australopithecus and Paranthropus crania from South and East Africa in future studies would further help establish morphological variability in these hominin taxa. PMID- 29793793 TI - Mechanical behavior of CAD/CAM occlusal ceramic reconstruction assessed by digital color holography. AB - OBJECTIVES: CAD/CAM ceramic occlusal veneers are increasingly used as therapeutic options. However, little is known about their mechanical behavior under stress, as the response of the prepared tooth that supports it. The aim of this article is to use for the first time 3D color holography to evaluate the behavior of a molar occlusal veneer under stress and the response of the prepared tooth. METHODS: The occlusal surface of a lower molar is prepared to receive a specific monolithic ceramic reconstruction manufactured with a chairside CAD/CAM system. Longitudinally cut samples are used to get a planar object observation and to "look inside" the tooth. A digital holographic set-up permits to obtain the contact-less and one-shot measurement of the three-dimensional displacement field at the surface of the tooth sample; stain fields are evaluated with low noise sensitive computation. RESULTS: Figures show the strain fields with micro-strain units and highlight the behavior of the ROI (region of interest) in the three directions of space. The ROI are: the ceramic, the glue junction, the dentin enamel junction, dentin and enamel. The results show an excellent behavior of the restored tooth without areas of excessive stress concentrations, but also a significant involvement of the dentin enamel junction. SIGNIFICANCE: The ceramic occlusal veneer seems to behave in accordance with the biomechanical concepts ensuring the longevity of the reconstituted tooth. 3D holography is a highly recommended method for studying dental biomechanics. PMID- 29793794 TI - Biaxial flexural strength of the bilayered disk composed of ceria-stabilized zirconia/alumina nanocomposite (Ce-TZP/A) and veneering porcelain. AB - OBJECTIVE: Herein we investigated the flexural strengths of bilayered ceria stabilized zirconia/alumina nanocomposite (Ce-TZP/A) disks using different veneering porcelains. METHODS: Commercial (VITA VM9, Cercon Ceram Kiss, and IPS e.max Ceram) and experimental porcelains (Vintage ZR with coefficient of thermal expansions: CTEs of 8.45, 9.04, and 9.61ppm/ degrees C) with various layer thicknesses (1.0, 1.5, and 2.0mm) were applied to Ce-TZP/A disks (0.8mm thickness, n=180). Biaxial flexural tests of the specimens with the porcelain layer in tension were evaluated based on the piston-on-three-ball method (ISO 6872: 2008). The calculated strengths were statistically analyzed using the two parameter Weibull distribution with the maximum likelihood estimation. RESULTS: Although no significant differences were observed among the experimental porcelains, most specimens with the thinner layer of commercial porcelain showed higher Weibull characteristic strengths at the external surfaces than those with the thicker layer. Irrespective of the porcelain material, the thinner porcelain layer showed significantly higher strengths at the interface between the layers. Fracture origins were always observed at the bottom surface and continuously propagated into Ce-TZP/A substrates. The maximum tensile stress was located at the interface in specimens with the 1.0mm porcelain layer, except for IPS e.max Ceram. Porcelain delamination was dominant in the case of the higher CTE value and thicker layer thickness of the porcelain. SIGNIFICANCE: The calculated biaxial flexural strengths and the stress distributions for bilayered Ce-TZP/A disks were dependent on the porcelain materials. Optimum behavior was observed for a combination of a small CTE mismatch between the materials and a low core-to porcelain thickness ratio. PMID- 29793796 TI - Emerging IL-12 family cytokines in the fight against fungal infections. AB - Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL-12p70, IL-23, IL-27 and IL-35) link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 and IL-23 have established roles during anti-fungal immunity, whereas emerging roles for IL 27 and IL-35 have recently been reported. Here, we discuss the IL-12 family, focusing on IL-27 and IL-35 during anti-fungal immune responses to pathogens such as Candida and Aspergillus. PMID- 29793795 TI - Effect of selective carious tissue removal on biomechanical behavior of class II bulk-fill dental composite restorations. AB - OBJECTIVES: This study aimed to develop a method to induce carious lesions in the pulpal floor dentin of a class II cavity preparation, and to determine the effects of this carious lesion on the biomechanical behavior of the dental composite restoration. METHODS: The pulpal floor dentin of class I cavities in sound third molars were demineralised with acetic acid for 35days followed by a 7 day exposure to pooled human saliva biofilm and demineralization was verified by micro-CT. Subsequently, the proximal walls were removed forming a class II cavity and the caries lesion was left intact or was completely removed prior to restoration with a bulk-fill dental composite (n=10). Cuspal deflection was assessed by strain-gauge and micro-CT imaging. The presence of enamel cracks was assessed by transillumination before and after restoration, and again after 1,200,000 cycles of mechanical fatigue in a chewing simulator. Finally, resistance to fracture by axial compressive loading and failure mode was determined. Data were analyzed by 2-way repeated measures ANOVA, Fisher's exact test, and t-test (alpha=0.05). RESULTS: The presence of carious lesions had no significant effect upon cuspal deflection, formation of enamel cracks, and fracture strength of the dental composite restorations. The restorative procedure increased the number of enamel cracks, which was not affected by mechanical cycling. SIGNIFICANCE: Maintaining carious lesions does not affect the biomechanical behavior of class II restorations performed with bulk-fill dental composite. PMID- 29793798 TI - The effects of platelet rich plasma on healing of full thickness burns in swine. AB - INTRODUCTION: Platelet rich plasma (PRP) is rich in growth factors and has been shown to improve healing in a variety of wounds. We determined the effects of PRP on healing and scarring in full thickness porcine burns with and without tangential excision and grafting (TEG). METHODS: Standardized full thickness 5cm by 5cm burns were created on each of the backs and flanks of 10 anesthetized female pigs (25kg) using a validated model. The burns were created with a heating device that emits heat at a temperature of 400 degrees C for a period of 30s. The burns were randomized to one of six treatments: no TEG or PRP, no TEG+PRP, early (day 2) TEG and no PRP, early TEG+PRP, late (day 14) TEG and no PRP, and late TEG+PRP. Tangential excision was performed down to viable tissue and autografts were 0.2mm thick. When used, a thin layer of autologous PRP was applied below the graft. All wounds were then treated with a topical antibiotic ointment 3 times weekly for 42 days. Digital images and full thickness biopsies were taken at 9, 11, 14, 18, 21, 28, 35 and 42days after injury to determine percentage reepithelialization, scar depth, and scar contraction. Tissue sections were stained with H&E and viewed by a dermatopathologist masked to treatment assignment. RESULTS: There was no reduction in platelet and white blood cell concentrations in PRP and blood samples for the first 14days after-full thickness burns. A total of 120 burns were created on 10 animals evenly distributed between the six treatment groups. Burns undergoing early TEG reepithelialized fastest and with the thinnest scars followed by late TEG. Burns that did not undergo TEG had the slowest reepithelialization and greatest amount of scarring. Application of PRP had no additional effects on reepithelialization, scar depth, or scar contraction in any of the treatment groups. CONCLUSIONS: Addition of PRP had similar effects on reepithelialization and scarring of full thickness porcine burns as standard topical antibiotic ointment regardless of whether the burns underwent excision or grafting or the timing of excision and grafting. PMID- 29793797 TI - Effect of blood transfusions on oncological outcomes of surgically treated localized renal cell carcinoma. AB - OBJECTIVE: To assess the associations between perioperative allogeneic blood transfusions (ABTs) and recurrence, overall and renal cell carcinoma (RCC) specific survival in patients undergoing surgical treatment for clinically localized disease. MATERIALS AND METHODS: We performed a retrospective review of 1,056 consecutive patients undergoing surgical treatment (radical or partial nephrectomy) for clinically localized RCC between 2000 to 2010. Demographic (age, race, and sex) clinical (preoperative hemoglobin and hematocrit, type of surgery [partial or radical nephrectomy]), and pathological (T and N stages, RCC histotype, grade) data were compared between patients receiving perioperative (intraoperative or postoperative) blood transfusions and those who are not. Distant and local recurrence-free survival, overall survival, RCC-specific survival were recorded and Kaplan-Meier survival curves as well as multivariable proportional regression models adjusted for clinical and pathological characteristics were produced. RESULTS: On multivariable analyses adjusted for clinical and pathological characteristics, the receipt of ABTs was associated with lower recurrence-free (HR = 1.86, P = 0.002), overall (HR = 1.83, P = 0.016), and RCC-specific survival (HR = 2.12, P = 0.031). The negative effect of ABTs was apparent for distant (HR = 2.24, P<0.001) but not local recurrences (HR = 0.78, P = 0.643). Limitations include retrospective nature and lack of uniform criteria for blood transfusion during the study period. CONCLUSIONS: In this study, perioperative ABTs were independently associated with worse oncological outcomes in patients with clinically localized RCC. Receipt of ABT was associated with roughly a 2-fold increase in the hazard of metastatic progression, all-cause and RCC-specific mortality. Further research is needed on the mechanisms of transfusion-induced immunomodulation, alternative transfusion protocols and methods for autologous blood transfusion and recovery. PMID- 29793799 TI - Caseload midwifery - A way forward for a model of care with historical roots. PMID- 29793800 TI - Haemodynamic responses of wearing low-pressure sports compression tights during an orthostatic challenge in healthy individuals. AB - OBJECTIVES: While previous studies have demonstrated an ergogenic effect of sport compression garments in exercise performance and recovery, the possible underlying mechanisms remain unclear. Claims for improved venous return from wearing sport compression garments with a low compression pressure remain unproven. The aim of this study was to determine the pressure profile exerted by low-pressure sports compression tights, and to investigate using a non-invasive Doppler ultrasound cardiac output monitor (USCOM), whether the compression applied will influence haemodynamic responses during an orthostatic challenge. DESIGN: A randomized-crossover design. METHODS: Thirty-three healthy participants (18 male and 15 female) underwent two trials, each consisting of lying supine and 70 degrees head-up tilt wearing either a low-pressure sports compression tights (CT) or track pants (CON). Stroke volume (SV) and cardiac output (CO) were measured non-invasively using USCOM; heart rate (HR) and non-invasive blood pressure were measured, and systemic vascular resistance (SVR) was derived. RESULTS: The SV and CO was lower at 70 degrees head-up tilt than in supine but wearing CT attenuated the decline in SV (25.9+/-11.6cm3 CT vs. 35.9+/-11.4cm3 CON, p<0.001), CO (1.1+/-0.7 Lmin-1 CT vs. 1.4+/-0.6 Lmin-1 CON, p<0.05), HR (8.8+/-8.4 beatmin-1 CT vs. 15.9+/-9.7 beatmin-1 CON, p<0.001) and SVR (740+/ 504dscm-5 CT vs. 961+/-560dscm-5 CON, p<0.005). The mean arterial pressure (3.3+/ 4.1mmHg CT vs. 3.6+/-4.5mm Hg CON, p>0.05) was similar in both trials. CONCLUSIONS: Healthy individuals wearing low-pressure sports compression tights experienced less severe haemodynamic disturbance such as decreases in CO, SV, HR and SVR during an orthostatic challenge. PMID- 29793802 TI - Post-stroke Movement Disorders: The Clinical, Neuroanatomic, and Demographic Portrait of 284 Published Cases. AB - PURPOSE: Abnormal movements are a relatively uncommon complication of strokes. Besides the known correlation between stroke location and certain movement disorders, there remain uncertainties about the collective effects of age and stroke mechanism on phenomenology, onset latency, and outcome of abnormal movements. MATERIALS AND METHODS: We systematically reviewed all published cases and case series with adequate clinical-imaging correlations. A total of 284 cases were analyzed to evaluate the distribution of different movement disorders and their association with important cofactors. RESULTS: Posterolateral thalamus was the most common region affected (22.5%) and dystonia the most commonly reported movement disorder (23.2%). The most common disorders were parkinsonism (17.4%) and chorea (17.4%) after ischemic strokes and dystonia (45.5%) and tremor (19.7%) after hemorrhagic strokes. Strokes in the caudate and putamen were complicated by dystonia in one third of the cases; strokes in the globus pallidus were followed by parkinsonism in nearly 40%. Chorea was the earliest poststroke movement disorder, appearing within hours, whereas dystonia and tremor manifested several months after stroke. Hemorrhagic strokes were responsible for most delayed-onset movement disorders (>6 months) and were particularly overrepresented among younger individuals affected by dystonia. CONCLUSIONS: This evidence-mapping portrait of poststroke movement disorders will require validation or correction based on a prospective epidemiologic study. We hypothesize that selective network vulnerability and resilience may explain the differences observed in movement phenomenology and outcomes after stroke. PMID- 29793801 TI - Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain. AB - BACKGROUND: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. MATERIALS AND METHODS: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. RESULTS: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8 OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. CONCLUSIONS: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain. PMID- 29793803 TI - Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation. AB - OBJECTIVES: For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation. METHODS: From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy. Women were followed from the date of completion of the baseline questionnaire until either a diagnosis of ovarian or fallopian tube cancer, prophylactic oophorectomy, death or last follow-up. The annual and cumulative incidence rates of ovarian cancer were estimated. RESULTS: Over a mean follow-up period of 4.7 years (ranges 0-22.6), 195 incident ovarian or fallopian tube cancers were diagnosed (169 [86%] ovarian cancers, 22 [11%] fallopian tube cancers and four [2%] cancers that involved both the ovaries and fallopian tubes). Of these, 45 (23%) cancers were diagnosed at preventive surgery (occult cancers). The cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA2 mutation carriers. The mean age at diagnosis was 51.3 years (ranges 33-84) among women with a BRCA1 mutation and 61.4 years (ranges 44-80) among women with a BRCA2 mutation. CONCLUSION: Based on a cumulative risk of 0.55% to age 35 for BRCA1 mutation carriers and of 0.56% to age 45 for BRCA2 mutation carriers, we recommend bilateral salpingo-oophorectomy before age 40, but ideally by age 35, for women with a BRCA1 mutation and by age 45 for those with a BRCA2 mutation to maximize prevention and to minimize adverse effects. PMID- 29793805 TI - Citizen Science: A Gateway for Innovation in Disease-Carrying Mosquito Management? AB - Traditional methods for tracking disease-carrying mosquitoes are hitting budget constraints as the scales over which they must be implemented grow exponentially. Citizen science offers a novel solution to this problem but requires new models of innovation in the public health sector. PMID- 29793804 TI - Massively parallel sequencing analysis of mucinous ovarian carcinomas: genomic profiling and differential diagnoses. AB - OBJECTIVE: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs. METHODS: Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome (n = 9) or massively parallel sequencing targeting 341 cancer genes (n = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites. RESULTS: MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A/B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS, TP53, CDKN2A, FBXW7, PIK3CA and/or APC mutations between the confirmed primary MOCs (n = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified. CONCLUSIONS: Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC. PMID- 29793807 TI - [Benign pulmonary metastases from a leiomyoma]. AB - INTRODUCTION: Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules. They can occur in women of reproductive age who have undergone hysterectomy for uterine leiomyoma. OBSERVATION: We report the case of a 46-year old women, who was incidentally found to have bilateral pulmonary cavitating nodules. Pathology exam was consistent with BML. CONCLUSION: Although BML is a rare cause of pulmonary nodules, it should be considered as one of the possibilities especially in young women with a history of hysterectomy for leiomyoma. PMID- 29793806 TI - Diverse Host and Restriction Factors Regulate Mosquito-Pathogen Interactions. AB - Mosquitoes transmit diseases that seriously impact global human health. Despite extensive knowledge of the life cycles of mosquito-borne parasites and viruses within their hosts, control strategies have proven insufficient to halt their spread. An understanding of the relationships established between such pathogens and the host tissues they inhabit is therefore paramount for the development of new strategies that specifically target these interactions, to prevent the pathogens' maturation and transmission. Here we present an updated account of the antagonists and host factors that affect the development of Plasmodium, the parasite causing malaria, and mosquito-borne viruses, such as dengue virus and Zika virus, within their mosquito vectors, and we discuss the similarities and differences between Plasmodium and viral systems, looking toward the elucidation of new targets for disease control. PMID- 29793808 TI - Best Practice for Implementation of the SCORE Portal in General Surgery Residency Training Programs. AB - INTRODUCTION: The Surgical Council on Resident Education (SCORE) has presented a workshop annually at the annual meeting of the Association of Program Directors (APDS) to discuss the evolution of the SCORE portal and best practices for implementation within residency training programs. METHODS/RESULTS: A review of the literature was undertaken, along with a summation of discussion at these several workshops. A history of the SCORE project and a summary of its organizational framework and content are presented. In addition, best practices for use of SCORE within programs are described. CONCLUSIONS: The SCORE portal is now a decade old, and is used ubiquitously in US surgical training programs. With this experience, there is data to show the utility of SCORE to support trainee learning and programmatic didactics. PMID- 29793810 TI - Call for Papers: MT/MTNA Special Issue on mRNA Therapy. PMID- 29793809 TI - DNA-Based Dynamic Reaction Networks. AB - Deriving from logical and mechanical interactions between DNA strands and complexes, DNA-based artificial reaction networks (RNs) are attractive for their high programmability, as well as cascading and fan-out ability, which are similar to the basic principles of electronic logic gates. Arising from the dream of creating novel computing mechanisms, researchers have placed high hopes on the development of DNA-based dynamic RNs and have strived to establish the basic theories and operative strategies of these networks. This review starts by looking back on the evolution of DNA dynamic RNs; in particular' the most significant applications in biochemistry occurring in recent years. Finally, we discuss the perspectives of DNA dynamic RNs and give a possible direction for the development of DNA circuits. PMID- 29793811 TI - Chronic Multifocal Paracoccidioidomycosis: Pulmonary and Cutaneous Involvement. PMID- 29793812 TI - Emergency Care for Children in the United States: Epidemiology and Trends Over Time. AB - BACKGROUND: The emergency care system for children in the United States is fragmented. A description of epidemiological trends based on emergency department (ED) volume over time could help focus efforts to improve emergency care for children. OBJECTIVES: To describe the trends of emergency care for children in the United States from 2006-2014 in EDs across different pediatric volumes. METHODS: We analyzed pediatric visits to EDs using the Health Care Utilization Project Nationwide Emergency Department Sample in a representative sample of 1,000 EDs annually from 2006-2014. We report trends in disease severity, mortality, and transfers based on strata by pediatric volume and other hospital characteristics. RESULTS: From 2006-2014, there were 318,114,990 pediatric ED visits. Pediatric visits remained steady but declined as a percentage of total visits (-3.91%, p = 0.0007). The majority (92.7%) of children were cared for in lower-volume EDs (<50,000 pediatric visits/year), where mortality was higher vs. the highest-volume EDs. Mortality decreased over time (0.34/1,000 to 0.27, p = 0.0099), whereas interhospital transfers increased (p = 0.0020). ED visits increased for children with Medicaid insurance (40.7% to 56.7%, p < 0.0001), whereas rates of self-pay insurance decreased (13.6% to 9.45%, p = 0.0006). The most common reasons for pediatric ED visits were trauma (25.6%); ear, nose, and throat; dental/mouth disorders (21.8%); gastrointestinal diseases (17.0%); and respiratory diseases (15.6%). CONCLUSIONS: Overall, pediatric ED visits have remained stable, with lower mortality rates, whereas Medicaid-funded pediatric visits have increased over time. Most children still seek care in lower-volume EDs. Efforts to improve pediatric care could be best focused on lower-volume EDs and interhospital transfers. PMID- 29793813 TI - Umbilical Hernia with Evisceration. Two Cases and a Review of the Literature. AB - BACKGROUND: Evisceration of umbilical hernias is an uncommon occurrence whereby the hernial contents break through the skin overlying the sac and skin. Irrespective of cause, sudden evisceration of an umbilical hernia is associated with deterioration and a poor outcome. CASE REPORTS: Our first case was a 42-year old woman who presented with sudden outpouring of fluid from the umbilicus with omental evisceration. Further evaluation revealed hepatic decompensation caused by hepatitis C infection belonging to Child-Turcotte-Pugh class C. After stabilizing her hemodynamically, she underwent a partial omentectomy with primary repair of umbilical defect. The patient's postoperative course was challenging. She died of septicemia and acute renal failure after 5 days. Our second case was a 40-year-old man who suffered from alcohol-induced cirrhosis, presenting with omental evisceration, belonging to Child-Turcotte-Pugh class C. We performed a primary repair of the hernial defect with peritoneovenous shunting for his intractable ascites. Upper gastrointestinal endoscopy revealed grade I esophageal varices. The patient succumbed to acute variceal hemorrhage with acute renal failure 18 days later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In an emergent setting with multiple factors influencing final surgical outcome, it is imperative that management be tailored for each patient. Those with severe encephalopathy or cardiovascular instability must be stabilized before surgical intervention. Central venous and blood pressures need to be closely monitored during resuscitation, as fervent fluid administration may predispose to variceal hemorrhage. It may be prudent to follow the principle of hypotensive resuscitation as in acute trauma cases. PMID- 29793814 TI - Chest Pain as a Manifestation of Intracranial Hypotension: Report of Four Cases. AB - BACKGROUND: Chest pain has not been recognized as a manifestation of intracranial hypotension secondary to cerebrospinal fluid leakage. CASE REPORT: We report on 4 patients with intracranial hypotension diagnosed by the pattern of headaches, temporal proximity to dural puncture, magnetic resonance imaging findings, and resolution of symptoms after epidural blood patch who presented with chest pain. The chest pain was episodic, located in the sternal and interscapular region for the first 3 patients, with no radiation to any other region and no clear relationship to exertion. The fourth patient had episodic chest pain located in the subclavicular and suprascapular region. Two patients reported dyspnea with chest pain. Underlying coronary artery ischemia was excluded using a combination of the electrocardiogram and cardiac enzyme assays. The pain resolved after epidural blood patch treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of chest pain that can be seen with intracranial hypotension and cerebrospinal leakage to ensure appropriate diagnostic tests and treatment. PMID- 29793816 TI - Predictors of falls and fractures leading to hospitalization in people with schizophrenia spectrum disorder: A large representative cohort study. AB - AIM: To investigate predictors of falls/fractures leading to hospitalisation in people with schizophrenia-spectrum disorders. METHODS: A historical cohort of people with schizophrenia-spectrum disorders (ICD F20-29) from 01/2006-12/2012 was assembled using data from the South London and Maudsley NHS Biomedical Research Centre Case Register. Falls/fractures were ascertained from a linkage to national hospitalisation data. Separate multivariate Cox regression analyses were employed to identify predictors of falls and fractures. RESULTS: Of 11,567 people with schizophrenia-spectrum disorders (mean age 42.6 years, 43% female), 579 (incidence rate 12.79 per 1000 person-years) and 528 (11.65 per 1000 person years) had at least one reported hospital admission due to a fall or fracture respectively and 822 patients had at least either a recorded fall or a fracture during this period (i.e. 7.1% of sample). Overall, 6.69 and 10.74 years of inpatient hospital stay per 1000-person years of follow-up occurred due to a fall and fracture respectively. 14(0.12%) and 28(0.24%) died due to a fall and fracture respectively. In Multivariable analysis, increasing age, white ethnicity, analgesics, cardiovascular disease, hypertension, diseases of the genitourinary system, visual disturbance and syncope were significant risk factor for both falls and fractures. A previous fracture (HR 2.05, 95% CI 1.53-2.73) and osteoporosis (HR 6.79, 95% CI 4.71-9.78) were strong risk factors for consequent fractures. CONCLUSION: Comorbid physical health conditions and analgesic medication prescription were associated with higher risk of falls and fractures. Osteoporosis and previous fracture were strong predictors for subsequent fractures. Interventions targeting bone health and falls/fractures need to be developed and evaluated in these populations. PMID- 29793817 TI - Increased plasticity of bodily self-experience in individuals who may carry latent liability for schizophrenia. AB - Self-disturbances such as altered perception of one's own body boundary are central to the lived-in experience of schizophrenia. Bodily self-disturbances are also prevalent in healthy individuals who may carry latent liability for schizophrenia. Much of the research on self-disturbances rely on clinical interviews but these experiences are often difficult to verbalize, conceptualize and quantify. Furthermore, experimental evidence for plasticity of bodily self experience in the schizophrenia-spectrum is scarce. We sought to quantify body boundary experience in healthy young adults who might be at an increased risk for schizophrenia with a multisensory paradigm known as the Pinocchio Illusion (PI) task that engenders the feeling that one's nose is changing, and has previously been used to demonstrate increased plasticity of bodily self-boundary in schizophrenia. 62 college students participated in the PI task that assessed bodily self-disturbances, and a tactile discrimination task. We administered the Prodromal Questionnaire Brief (PQ-B) and the Schizotypal Personality Questionnaire (SPQ) to assess latent liability for schizophrenia. We found that PI was enhanced in individuals with elevated PQ-B scores but their tactile sensitivity was intact. PI was associated with the positive syndrome of schizotypy, but not with negative or disorganized factors. Increased PQ-B and SPQ scores were associated with loneliness. To conclude, these results highlight the importance of bodily self-disturbances in the broader context of the schizophrenia spectrum. PMID- 29793815 TI - Multidomain Quantitative Recovery Following Radical Cystectomy for Patients Within the Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion Versus Open Radical Cystectomy Randomised Controlled Trial: The First 30 Patients. PMID- 29793818 TI - Evidence that the association of childhood trauma with psychosis and related psychopathology is not explained by gene-environment correlation: A monozygotic twin differences approach. AB - BACKGROUND: Converging evidence supports childhood trauma as possible causal risk for psychosis and related psychopathology. However, studies have shown that baseline psychotic symptoms may actually increase risk for subsequent victimization, suggesting that exposure to CT is not random but may result from pre-existing vulnerability. Therefore, studies testing whether the association between CT and psychopathology persists when accounting for gene-environment correlation are much needed. METHODS: A monozygotic (MZ) twin differences approach was used to examine whether differences in CT exposure among MZ twin pairs would be associated with MZ differences in symptoms. As MZ twins are genetically identical, within-pair correlations between CT exposure and psychopathology rule out the possibility that the association is solely attributable to gene-environment correlation. 266 monozygotic twins (133 pairs) from a larger general population study were available for analysis. RESULTS: CT was associated with symptoms of psychosis (B = 0.62; SE = 0.08, p < .001) and overall psychopathology (B = 43.13; SE = 6.27; p < .001). There were measurable differences within pairs in CT exposure and symptoms, allowing for meaningful within-pair differences. Within-pair differences in CT exposure were associated with within-pair differences in symptoms of psychosis (B = 0.35; SE = 0.16; p = .024), as well as with overall psychopathology (B = 29.22; SE = 12.24; p = .018), anxiety (B = 0.65; SE = 0.21; p = .002) and depression (B = 0.37; SE = 0.18; p = .043). CONCLUSION: While it is not unlikely that pre-existing vulnerability may increase the risk for traumatic exposures, such gene-environment correlation does not explain away the association between CT and psychopathology. The present findings thus suggest that at least part of the association between CT and psychopathology may be causal. PMID- 29793819 TI - Editor's notes. PMID- 29793820 TI - Emerging stem cell based strategies for treatment of childhood diseases. AB - Cell therapy is an important regenerative medicine approach, in which either differentiated cells or stem cells capable of differentiation are transplanted into an individual with the objective of yielding specific cell types in the damaged tissue and consequently restoring its function. The most successful example of cell therapy is hematopoietic stem cell transplantation, leading to regeneration of patient's blood cells, now a widely established procedure for many hematopoietic diseases. Development of cellular therapies for other tissues then followed in the footsteps of the hematopoietic experience. Nowadays, there are numerous ongoing clinical trials using various types of stem cells and some of them become approved cell-based products for use by patients. The aim of this review is to highlight some of advances and challenges of cell-based therapies including. PMID- 29793822 TI - Eliminating cystic echinococcosis in the 21st century. PMID- 29793821 TI - Epidemiology and patient-reported outcome after juvenile osteochondritis dissecans in the knee. AB - BACKGROUND: This study describes the epidemiology and patient reported outcomes following juvenile osteochondritis dissecans (JOCD) of the knee. METHODS: Medical records and radiographs of patients aged 10-18years diagnosed with JOCD between 2010 and 2016 were retrospectively reviewed. The lesions were classified according to the International Cartilage Repair Society's classification. The results were evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS), the Lysholm score and a Visual Analogue Scale (VAS) for pain. RESULTS: Seventy patients with 87 JOCDs were identified. The annual incidence was 11.5 (95% confidence interval 10.7-12.2) per 100,000 inhabitants younger than 19years. Fifty-two (74.3%) of the 70 patients returned the questionnaires on average 48months (five to 117) after diagnosis. The median Lysholm score was 84 for patients with grade I-II lesions and 80 for patients with grade III-IV lesions. The median Lysholm score was 84.5 for patients who were treated conservatively and 79.5 for patients who were treated operatively. The median VAS score was 2.0 for all groups, except for patients treated conservatively (median score 1.5). Conservative treatment was successful in 78% of grade I-II lesions. There was a fivefold increased risk of failing conservative treatment with a stage III-IV lesion, compared to stage I-II (Odds ratio=5.5, p=0.02). CONCLUSIONS: The results following JOCD are good to excellent for the majority of patients. Grade I-II lesions are successfully treated conservatively in 78% of cases. Grade III-IV lesions have a high failure rate. LEVEL OF EVIDENCE: Level III, retrospective cohort. PMID- 29793823 TI - Prevalence of abdominal cystic echinococcosis in rural Bulgaria, Romania, and Turkey: a cross-sectional, ultrasound-based, population study from the HERACLES project. AB - BACKGROUND: Cystic echinococcosis is a neglected zoonotic infection that is distributed worldwide and prioritised by WHO for control efforts. The burden of human cystic echinococcosis is poorly understood in most endemic regions, including eastern Europe. We aimed to estimate the prevalence of abdominal cystic echinococcosis in rural areas of Bulgaria, Romania, and Turkey. METHODS: We did a cross-sectional ultrasound-based survey that recruited volunteers from 50 villages in rural areas of Bulgaria, Romania, and Turkey. These villages were in provinces with annual hospital incidence of cystic echinococcosis within the mid range for the respective countries. All people who attended a session were allowed to participate if they agreed to be screened. Abdominal ultrasound screening sessions were hosted in public community structures such as community halls, primary health-care centres, schools, and mosques. Lesions were classified using an adapted WHO classification. We reported the prevalence of abdominal cystic echinococcosis adjusted by sex and age through direct standardisation, using the country's rural population as a reference. FINDINGS: From July 1, 2014, to Aug 3, 2015, 24 693 individuals presented to screening sessions and 24 687 underwent ultrasound screening. We excluded a further six indivduals due to missing data, leaving 24 681 people in our analysis. Abdominal cystic echinococcosis was detected in 31 of 8602 people screened in Bulgaria, 35 of 7461 screened in Romania, and 53 of 8618 screened in Turkey. The age and sex adjusted prevalence of abdominal cystic echinococcosis was 0.41% (95% CI 0.29-0.58) in Bulgaria, 0.41% (0.26-0.65) in Romania, and 0.59% (0.19-1.85) in Turkey. Active cysts were found in people of all ages, including children, and in all investigated provinces. INTERPRETATION: Our results provide population-based estimates of the prevalence of abdominal cystic echinococcosis. These findings should be useful to support the planning of cost-effective interventions, supporting the WHO roadmap for cystic echinococcosis control. FUNDING: European Union Seventh Framework Programme. PMID- 29793825 TI - Chronic myeloproliferative neoplasms in the elderly. AB - This review focuses on the management of elderly patients with chronic myeloid leukemia and chronic myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis. Median age in these neoplasms is within the 6th decades of age. All new therapies can be done at any age without absolute contraindication. However, the selection of the precise therapy for the single patient is mandatory. For these reasons, an accurate definition of diagnosis and prognostication is necessary. Precision in disease definition and prognostication is definitively helpful for personalizing therapeutic approach. PMID- 29793824 TI - Effects of glycemic variability and hyperglycemia in acute ischemic stroke on post-stroke cognitive impairments. AB - AIMS: We aimed to investigate the effect of glycemic variability in the acute stage of stroke on the development of post-stroke cognitive impairment (PSCI). METHODS: Patients who underwent blood glucose tests at least five times within 7 days after acute ischemic stroke were included. Factors related to glycemic variability (standard deviation (SD), coefficient of variance (CV), and mean absolute glucose (MAG)) were calculated; neuropsychological assessments were administered 3 months after stroke. PSCI was defined as a score of less than -2 SDs for age-, sex-, and education-adjusted means in at least one cognitive domain. RESULTS: A total of 354 patients were enrolled. PSCI was identified in 74 (20.9%) subjects. In the diabetic group (n = 87), MAG was a significant predictor for PSCI (adjusted OR, 1.94; 95% CI, 1.11-3.42); however, it was not significant in the non-diabetic group, although PSCI exhibited an increasing tendency within higher SD and MAG tertiles. Moreover, hyperglycemia demonstrated a detrimental effect on PSCI, regardless of diabetes status; this effect did not appear in poorly-controlled diabetic patients with HbA1c >= 8.0%. CONCLUSIONS: Glycemic variability and hyperglycemia during acute ischemic stroke were identified as novel predictors for PSCI. Although this result is not evidence of a causal relationship, our study suggests that monitoring glycemic index and controlling its variability during the acute phase of ischemic stroke may help to prevent poor cognitive outcomes. PMID- 29793826 TI - Investigation of cracking and water availability of soil-biochar composite synthesized from invasive weed water hyacinth. AB - Water hyacinth (WH), is one of the world's most intractable and invasive weed species. Recent studies explored the efficacy of this species as a biochar (BC) in improving soil fertility and metal adsorption. However, the soil water retention (SWR) property and crack potential of soil-WH biochar composite has still not been studied. The major objective of this study is to investigate the SWR property and corresponding crack intensity factor (CIF) for compacted soil-WH BC composites. Soil-WH BC composites at five percentages (0, 2, 5, 10 and 15) was compacted and soil parameters such as suction (psi), water content and CIF were simultaneously monitored for 63 days (including 9 drying-wetting cycles). Results showed that soil-WH BC composite at all percentages retains more water (max. 19% and min. 6.53%) than bare soil at both saturated and drought conditions. Gradual inclusion of WH BC to soil decreases the CIF potential from 7% to 2.8%. PMID- 29793827 TI - Nontypeable Haemophilus influenzae (NTHi). AB - In this infographic the diseases caused by nontypeable Haemophilus influenzae (NTHi), including otitis media, are discussed. Encapsulated type b Haemophilus influenzae (Hib) was responsible for most of the invasive disease (meningitis) prior to the use of Hib vaccines. As Hib vaccines have no effect on infections due to nontypeable H. influenzae (NTHi), in areas where Hib vaccines are used, nontypeable strains are now the most common cause of invasive disease. Moreover, NTHi contributes to the ~21000 otitis media (OM)-associated deaths per year. Due to this collective global morbidity and mortality, concerted vaccine development is underway. In addition to preventing disease, an effective vaccine will likely help to mitigate the global crisis of antibiotic resistance. Since 1973, ampicillin resistance due to NTHi's production of beta-lactamase has been recognized; however, a significant concern is the more recent emergence and spread of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains in many regions of the world. As such, H. influenzae is one of 12 bacterial pathogens that are considered priority pathogens by the World Health Organization. PMID- 29793829 TI - Best practices for the use of intracerebroventricular drug delivery devices. AB - For decades, intracerebroventricular (ICV), or intraventricular, devices have been used in the treatment of a broad range of pediatric and adult central nervous system (CNS) disorders. Due to the limited permeability of the blood brain barrier, diseases with CNS involvement may require direct administration of drugs into the brain to achieve full therapeutic effect. A recent comprehensive literature review on the clinical use and complications of ICV drug delivery revealed that device-associated complication rates are variable, and may be as high as 33% for non-infectious complications and 27% for infectious complications. The variability in reported safety outcomes may be driven by a lack of consensus on best practices of device use. Numerous studies have demonstrated that employing strict aseptic techniques and following stringent protocols can dramatically reduce complications. Key practices to be considered in facilitating the safe, long-term use of these devices are presented. PMID- 29793830 TI - Start-up of a Cardiology Day Hospital: Activity, Quality Care and Cost effectiveness Analysis of the First Year of Operation. AB - INTRODUCTION AND OBJECTIVES: The cardiology day hospital (CDH) is an alternative to hospitalization for scheduled cardiological procedures. The aims of this study were to analyze the activity, quality of care and the cost-effectiveness of a CDH. METHODS: An observational descriptive study was conducted of the health care activity during the first year of operation of DHHA. The quality of care was analyzed through the substitution rate (outpatient procedures), cancellation rates, complications, and a satisfaction survey. For cost-effectiveness, we calculated the economic savings of avoided hospital stays. RESULTS: A total of 1646 patients were attended (mean age 69 +/- 15 years, 60% men); 2550 procedures were scheduled with a cancellation rate of 4%. The most frequently cancelled procedure was electrical cardioversion. The substitution rate for scheduled invasive procedures was 66%. Only 1 patient required readmission after discharge from the CDH due to heart failure. Most surveyed patients (95%) considered the care received in the CDH to be good or very good. The saving due to outpatient converted procedures made possible by the CDH was ? 219 199.55, higher than the cost of the first year of operation. CONCLUSIONS: In our center, the CDH allowed more than two thirds of the invasive procedures to be performed on an outpatient basis, while maintaining the quality of care. In the first year of operation, the expenses due to its implementation were offset by a significant reduction in hospital admissions. PMID- 29793828 TI - Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men. AB - BACKGROUND: Exogenous testosterone decreases serum concentrations of high-density lipoprotein cholesterol (HDL-C) in men, but whether this alters cardiovascular risk is uncertain. OBJECTIVE: To investigate the effects of testosterone and estradiol on HDL particle concentration (HDL-Pima) and metrics of HDL function. METHODS: We enrolled 53 healthy men, 19 to 55 years of age, in a double-blinded, placebo-controlled, randomized trial. Subjects were rendered medically castrate using the GnRH receptor antagonist acyline and administered either (1) placebo gel, (2) low-dose transdermal testosterone gel (1.62%, 1.25 g), (3) full replacement dose testosterone gel (1.62%, 5 g) or (4) full replacement dose testosterone gel together with an aromatase inhibitor for 4 weeks. At baseline and end of treatment, serum HDL total macrophage and ABCA1-specific cholesterol efflux capacity (CEC), HDL-Pima and size, and HDL protein composition were determined. RESULTS: Significant differences in serum HDL-C were observed with treatment across groups (P = .01 in overall repeated measures ANOVA), with increases in HDL-C seen after both complete and partial testosterone deprivation. Medical castration increased total HDL-Pima (median [interquartile range] 19.1 [1.8] nmol/L at baseline vs 21.3 [3.1] nmol/L at week 4, P = .006). However, corresponding changes in total macrophage CEC and ABCA1-specific CEC were not observed. Change in serum 17beta-estradiol concentration correlated with change in total macrophage CEC (beta = 0.33 per 10 pg/mL change in serum 17beta estradiol, P = .03). CONCLUSIONS: Testosterone deprivation in healthy men leads to a dissociation between changes in serum HDL-C and HDL CEC. Changes in serum HDL-C specifically due to testosterone exposure may not reflect changes in HDL function. PMID- 29793831 TI - Illustrating the potency of current Good Manufacturing Practice-compliant induced pluripotent stem cell lines as a source of multiple cell lineages using standardized protocols. AB - BACKGROUND AIMS: We have previously reported the generation of a current Good Manufacture Practice (cGMP)-compliant induced pluripotent stem cell (iPSC) line for clinical applications. Here we show that multiple cellular products currently being considered for therapy can be generated from a single master cell bank of this or any other clinically compliant iPSC line METHODS: Using a stock at passage 20 prepared from the cGMP-compliant working cell bank (WCB), we tested differentiation into therapeutically relevant cell types of the three germ layers using standardized but generic protocols. Cells that we generated include (i) neural stem cells, dopaminergic neurons and astrocytes; (ii) retinal cells (retinal pigment epithelium and photoreceptors); and (iii) hepatocyte, endothelial and mesenchymal cells. To confirm that these generic protocols can also be used for other iPSC lines, we tested the reproducibility of our methodology with a second clinically compliant line RESULTS: Our results confirmed that well-characterized iPSC lines have broad potency, and, despite allelic variability, the same protocols could be used with minimal modifications with multiple qualified lines. In addition, we introduced a constitutively expressed GFP cassette in Chr13 safe harbor site using a standardized previously described method and observed no significant difference in growth and differentiation between the engineered line and the control line indicating that engineered products can be made using a standardized methodology CONCLUSIONS: We believe that our demonstration that multiple products can be made from the same WCB and that the same protocols can be used with multiple lines offers a path to a cost-effective strategy for developing cellular products from iPSC lines. PMID- 29793832 TI - The assessment of movement health in clinical practice: A multidimensional perspective. AB - This masterclass takes a multidimensional approach to movement assessment in clinical practice. It seeks to provide innovative views on both emerging and more established methods of assessing movement within the world of movement health, injury prevention and rehabilitation. A historical perspective of the value and complexity of human movement, the role of a physical therapist in function of movement health evaluation across the entire lifespan and a critical appraisal of the current evidence-based approach to identify individual relevant movement patterns is presented. To assist a physical therapist in their role as a movement system specialist, a clinical-oriented overview of current movement-based approaches is proposed within this multidimensional perspective to facilitate the translation of science into practice and vice versa. A Movement Evaluation Model is presented and focuses on the measurable movement outcome of resultants on numerous interactions of individual, environmental and task constraints. The model blends the analysis of preferred movement strategies with a battery of cognitive movement control tests to assist clinical judgement as to how to optimize movement health across an individual lifespan. PMID- 29793834 TI - Editorial commentary: Plant-based diets: More than meets the eye. PMID- 29793833 TI - Early anterior knee pain in male adolescent basketball players is related to body height and abnormal knee morphology. AB - OBJECTIVES: To compare knee torque, range of motion, quality of movement, and morphology in dominant and nondominant legs of male adolescent basketball players with and without anterior knee pain and untrained peers. DESIGN: Cross-sectional. SETTING: Sports performance laboratory. PARTICIPANTS: Male basketball players aged 14-15 years with and without anterior knee pain and healthy untrained subjects (n = 88). MAIN OUTCOME MEASURES: Basketball players were allocated to a symptomatic or asymptomatic group based on self-reported anterior knee pain. Associations between pain and body mass, height, passive range of motion, muscle peak torque, coactivation, neuromuscular control, proprioception, and ultrasound observations were investigated. RESULTS: The prevalence of pain did not differ significantly between sides. Of 176 knees inspected, 44 were painful, and 26 of these exhibited abnormalities in ultrasonography. Symptomatic players were 5.0 and 6.9 cm taller than asymptomatic players and controls, respectively (P < 0.05). In athletes with knee pain, the odds ratios of morphological abnormalities and greater height were increased by 8.6 and 5.0 times (P < 0.001). CONCLUSION: Knee pain prevalence in adolescent basketball players was not related to differences between sides but was higher in tall players. Knee pain was accompanied by morphological abnormalities detected with ultrasound. PMID- 29793835 TI - Good Relationships Mean Good Reimbursement. PMID- 29793836 TI - Estimated Mortality of Breast Cancer Patients Based on Stage at Diagnosis and National Screening Guideline Categorization. AB - PURPOSE: To compare overall and stage I to IV mortalities of patients diagnosed with breast cancer, calculated from stage at diagnosis using the Surveillance, Epidemiology, and End Results (SEER) database stage mortality estimates, which are based on national screening guideline categorization. METHODS: From the stage at diagnosis of new breast cancer patients between 2010 and 2014, percentages of invasive cancers, stage 0 + I of total cancers, and stage I of invasive cancers, were calculated. Five-year estimated overall and invasive mortalities were calculated based on stage at diagnosis and SEER survival data. Program categories defined included an Annual Program, based on the ACR (annual screening age 40 and above), a Biennial Program, based on the US Preventative Services Taskforce (biennial screening ages 50 to 74 years), and a Hybrid Program, based on the American Cancer Society (annual screening ages 45 to 54 years, then biennially at ages 55 and above), including respective interval cancers. RESULTS: In all, 445 breast cancers met the study inclusion criteria. Comparing program categories, the Annual Program had the lowest percentage of invasive cancers (75.3%), highest percentages of stage 0 + I of total cancers (75.3%) and stage I of invasive cancers (67.1%), and the lowest 5-year estimated overall (10.1%) and stage I to IV (12.0%) mortalities. Estimated overall and stage I to IV mortalities for the Annual Program was 37.3% and 30.6% less, respectively, than the Biennial Program, and 31.8% and 26.8% less, respectively, than the Hybrid Program. CONCLUSIONS: Based on stage at diagnosis, the greatest mortality reduction is achieved with mammography utilization starting at the age of 40. PMID- 29793837 TI - Ionizing Radiation Use and Cancer Predisposition Syndromes in Children. PMID- 29793838 TI - Central composite design parameterization of microalgae/cyanobacteria co-culture pretreatment for enhanced lipid extraction using an external clamp-on ultrasonic transducer. AB - Lipids extracted from algal biomass could provide an abundant, rapidly growing, high yield feedstock for bio-diesel and other green fuels to supplement current fossil-based sources. Ultrasound pretreatment is a mechanical cell disruption method that has been shown to enhance lipid recovery from algae due to cavitation effects that disrupt algae cell walls. In this study, a locally grown mixture of Chlorella vulgaris/Cyanobacteria leptolyngbya was sonicated in an ultrasonic reactor with a clamp-on transducer prior to solvent lipid extraction. This configuration allows for a non-contact delivery method of ultrasonic energy with improved operational advantages (no fouling of transducer, continuous operation, and fully scalable design). A central composite design (CCD) was implemented to statistically analyze and evaluate the effect of ultrasonic power (350-750 W) and treatment time (5-30 min) on lipid yield. Lipid recovery was found to increase with both ultrasonic power and treatment time. Total lipid yields (on dry biomass basis) extracted via the Bligh and Dyer method from Chlorella vulgaris/cyanobacteria co-culture ranged from 8.3% for untreated algae to 16.9% for algae sonicated with 750 W power for 30 min, which corresponds to more than a doubling of lipid recovery due to ultrasound pretreatment. Increased power and treatment times were found to increase the degree of cell disruption as observed in the SEM and TEM images after ultrasonic pretreatment. Additionally, hexane (1:1 v/v) was evaluated as an alternative to the standard Bligh & Dyer (2:2:1.8 v/v/v chloroform/methanol/cell suspension) lipid extraction solvent system. On average, the Bligh and Dyer method extracted on average over twice the amount of lipids compared to hexane extraction. The lipid profile of the algae extracts indicates high concentrations of lauric acid (12:0), palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2). This particular configuration of an ultrasonic system proved to be a viable method for the pretreatment of algae for enhanced lipid yields. Future research should focus on identifying alternative extraction solvents and expanding the range of treatment conditions to optimize the ultrasonic power and treatment times for maximum lipid recovery. PMID- 29793839 TI - International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club. AB - BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of Early CP is not possible using imaging criteria alone. If this were possible and early treatment instituted, the later, irreversible features and complications of CP could possibly be prevented. METHOD: An international working group supported by four major pancreas societies (IAP, APA, JPS, and EPC) and a PancreasFest working group sought to develop a consensus definition and diagnostic criteria for Early CP. Ten statements (S1-10) concerning Early CP were used to gauge consensus on the Early CP concept using anonymous voting with a 9 point Likert scale. Consensus required an alpha >=0.80. RESULTS: No consensus statement could be developed for a definition of Early-CP or diagnostic criteria. There was consensus on 5 statements: (S2) The word "Early" in early chronic pancreatitis is used to describe disease state, not disease duration. (S4) Early CP defines a stage of CP with preserved pancreatic function and potentially reversible features. (S8) Genetic variants are important risk factors for Early CP and can add specificity to the likely etiology, but they are neither necessary nor sufficient to make a diagnosis. (S9) Environmental risk factors can provide evidence to support the diagnosis of Early CP, but are neither necessary nor sufficient to make a diagnosis. (S10) The differential diagnosis for Early CP includes other disorders with morphological and functional features that overlap with CP. CONCLUSIONS: Morphology based diagnosis of Early CP is not possible without additional information. New approaches to the accurate diagnosis of Early CP will require a mechanistic definition that considers risk factors, biomarkers, clinical context and new models of disease. Such a definition will require prospective validation. PMID- 29793840 TI - Bacterial interspecies quorum sensing in the mammalian gut microbiota [C. R. Biologies 341 (2018) https://doi.org/10.1016/j.crvi.2018.03.006]. PMID- 29793841 TI - Assessing comfort in the epilepsy monitoring unit: Development of an instrument. AB - BACKGROUND/PURPOSE: Some patients perceive the experience of hospitalization in an epilepsy monitoring unit (EMU) to be an uncomfortable one. In order to provide comfort-enhancing measures, nurses need to assess comfort levels. For this purpose, Kolcaba developed the General Comfort Questionnaire (GCQ), which may be modified for usage in specific settings. The objective of this study was to develop an instrument to assess comfort of adult patients during hospitalization in an EMU, namely the Epilepsy Monitoring Unit Comfort Questionnaire (EMUCQ). METHODS: The GCQ was translated from American English into German following the guidelines of the International Society for Pharmacoeconomics and Outcome Research (ISPOR). Three native German speakers with good command of the English language did forward translations. An expert who grew up bilingual did a backtranslation. For use in an EMU, literature-based setting-specific items were added. In a qualitative-descriptive study, cognitive debriefing with 25 patients was conducted using cognitive interviews. Qualitative data analysis was based on the framework method. In a quantitative-descriptive study, nine clinical experts assessed content validity. RESULTS: For setting-specific modification, 12 items pertaining to surroundings, feeling observed, and feeling afraid of a seizure were added to the translated GCQ. Based on the initial content validity rating, 26 items remained unchanged, 12 items underwent revisions, and 14 items were omitted. Eight items were put aside for a follow-up rating in the context of cognitive debriefing. Cognitive interviewing revealed problems regarding the interpretation of items and missing items. According to the results, 27 items remained unchanged, 11 items were reworded, and six items were added. The final content validity rating showed item-content validity indices (I-CVI) between .33 and 1, and an average CVI on a scale level (S-CVI/ave) of .84. CONCLUSIONS: Enhancing comfort is a fundamental nursing goal in demanding situations. Therefore, the contribution of nurses to the quality of individualized patient care is a substantial one. The EMUCQ is a valuable tool to support the assessment of comfort levels. The ISPOR guidelines proved to be useful to ensure high quality of the translated instrument. Using cognitive interviews enhanced the understandability of items and supported modification of the GCQ. At present, S CVI/ave value of the EMUCQ is acceptable. Further testing is necessary. PMID- 29793842 TI - 18F-choline PET/MRI in suspected recurrence of prostate carcinoma. AB - OBJECTIVE: To evaluate the usefulness of simultaneous 18F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18F-choline PET/MRI detection rate with analytical and pathological variables. MATERIAL AND METHODS: 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. RESULTS: 18F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSAmed) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSAmed in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSAmed 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6 9), without statistically significant differences. CONCLUSION: 18F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18F-choline PET/MRI detection rate was not statistically significant. PMID- 29793843 TI - Clinical and nutritional outcome of pediatric esophageal stenosis with endoscopic balloon dilatation. AB - AIM: The present study evaluates the long-term clinical and nutritional effect to endoscopic balloon dilatation (EBD) in pediatric esophageal stricture. METHODS: This was a 15-year retrospective study involving pediatric patients with esophageal stricture treated with EBD. Outcome parameters included the number of dilatations, procedural success rates, nutritional status, and complications. EBD was performed in patients with a dysphagia score greater than 2. The nutritional status was assessed by weight-for-age z-score. Clinical success was defined as no requirement for EBD for at least 1 year and/or increasing interval between dilatation and the numbers of EBD was fewer than 4 times per year. RESULTS: A total of 50 cases (mean age, 4.41 +/- 4.9 years) were enrolled. During a mean follow-up of 3.2 +/- 1.9 years, a total of 268 EBD sessions were performed, with an average of 5.36 sessions per patient (range, 1-33). Patients who had short segment stricture (<2 cm) were prone to achieve clinical success after EBD (p = 0.0094). Procedural perforation rate is 2.6% (7/268); subsequent tracheoesophageal fistula occurred in two patients. The clinical success rate of EBD therapy was 72% (36/50). All had increments of weight-for-age z-score after EBD therapy, and the increment was significantly greater in those patients with short segment stricture or stricture in the middle esophagus at 12 months (p = 0.01 and 0.008, respectively). CONCLUSIONS: EBD has good long-term clinical success and nutritional promotion in pediatric patients with esophageal stricture, especially in short segment stricture or stricture in the middle esophagus. PMID- 29793844 TI - Wound Outcomes in Negative Pressure Dressings (WOUND) study - A randomised trial in lower limb skin cancer grafts. PMID- 29793845 TI - Review of educational interventions to increase traditional birth attendants' neonatal resuscitation self-efficacy. AB - BACKGROUND: Annually, up to 2.7 million neonatal deaths occur worldwide, and 25% of these deaths are caused by birth asphyxia. Infants born in rural areas of low and-middle-income countries are often delivered by traditional birth attendants and have a greater risk of birth asphyxia-related mortality. AIM: This review will evaluate the effectiveness of neonatal resuscitation educational interventions in improving traditional birth attendants' knowledge, perceived self-efficacy, and infant mortality outcomes in low-and-middle-income countries. METHODS: An integrative review was conducted to identify studies pertaining to neonatal resuscitation training of traditional birth attendants and midwives for home-based births in low-and-middle-income countries. Ten studies met inclusion criteria. FINDINGS: Most interventions were based on the American Association of Pediatrics Neonatal Resuscitation Program, World Health Organization Safe Motherhood Guidelines and American College of Nurse-Midwives Life Saving Skills protocols. Three studies exclusively for traditional birth attendants reported decreases in neonatal mortality rates ranging from 22% to 65%. These studies utilized pictorial and oral forms of teaching, consistent in addressing the social cognitive theory. Studies employing skill demonstration, role-play, and pictorial charts showed increased pre- to post-knowledge scores and high self efficacy scores. In two studies, a team approach, where traditional birth attendants were assisted, was reported to decrease neonatal mortality rate from 49-43/1000 births to 10.5-3.7/1000 births. CONCLUSION: Culturally appropriate methods, such as role-play, demonstration, and pictorial charts, can contribute to increased knowledge and self-efficacy related to neonatal resuscitation. A team approach to training traditional birth attendants, assisted by village health workers during home-based childbirths may reduce neonatal mortality rates. PMID- 29793846 TI - Feminizing genitoplasties: Where are we now? AB - INTRODUCTION: Feminizing genitoplasties (FG) are controversial, because of possible adverse effects on sex life. Some have suggested limiting surgery to children presenting health problems related to their genital abnormality and patients who may give their informed consent. This paper analyzes research data about late results of FG, to substantiate the choice of whether to operate on children or to limit surgery to adults/adolescents. STUDY DESIGN: Review and synthesis of the literature about late results of FG. RESULTS: Eleven papers were found, involving different primary diseases and techniques (levels of evidence 3 4). There are no long-term data about corporeal sparing clitoroplasty, ASTRA procedures, and urogenital sinus mobilization. Surgery alters objective genital sensitivity, but most patients attest good subjective post-operative clitoral sensation. Complaints of poor clitoral sensation were related to reoperations, amputation, recession, atrophy, or neurovascular bundle injuries. CAH homozygous (null) genotypes show worse sensitivity and sex life, independent of surgery. Sexual function and avoidance are comparable between post-operated and virgin CAH patients. Problems with global auto-image were related to sexual difficulties. Introitus stenosis is frequent. Patients rarely reported distress concerning FG but vaginal self-dilatation is traumatic. Most patients operated on as young children evaluated timing of their surgery as correct. DISCUSSION: Biological, technical, and subjective factors influence females' attitudes towards sexual satisfaction. FG patients tend to be sexually insecure. Some sequelae described in adult women should be uncommon in contemporaneous cohorts, because of new techniques. CONCLUSION: Evidence about long-term sequelae of FG are of low quality and methodologically limited by unphysiological sensitivity measurement methods that do not correspond to subjective reports of the patients. Modern techniques have not been evaluated in the long term. The consequences of intentionally raising severely virilized children as females in our contemporaneous society have not been studied: such a decision still represents a social experiment. PMID- 29793847 TI - Improvement in LDL is associated with decrease in non-calcified plaque volume on coronary CTA as measured by automated quantitative software. AB - BACKGROUND: Computed tomography coronary angiography (CTA) can be used for assessment of plaque characteristics; however, quantitative assessment of changes in plaque composition in response to LDL lowering has not been performed with CTA. We sought to assess the association between LDL reduction and changes in plaque composition with quantitative CTA. METHODS: Quantification of total, calcified, non-calcified and low-density non-calcified plaque volumes (TPV, CPV, NCPV and LD-NCPV) was performed using semi-automated software in 234 vessels from 116 consecutive patients (89 men, 60 +/- 10 years) with baseline LDL>70 mg/dl. Significant reduction in LDL was defined as a decrease by >10% of baseline LDL. Changes (Delta) in plaque volumes between the second and baseline study were compared between patients with LDL reduction (n = 63) and those with no decrease in LDL (n = 53). RESULTS: Median LDL at baseline was 98 mg/dl [interquartile range (IQR) 83-119 mg/dl] and median DeltaLDL was -14 mg/dl (IQR -38 to 3 mg/dl). Mean interval between sequential CTA was 3.5 +/- 1.6 years. TPV, NCPV, and LD NCPV decreased in patients with a reduction in LDL compared to baseline; whereas, patients without reduction in LDL experienced an increase in TPV, NCPV and LD NCPV. After adjusting for age, statin use, diabetes, baseline LDL and baseline TPV, reduction in LDL was associated with a decrease in TPV (P = 0.005), NCPV (P = 0.002) and LD-NCPV (P = 0.011) compared to patients without a reduction in LDL. CONCLUSION: Reduction in LDL was associated with beneficial changes in the amount and composition of noncalcified plaque as measured using semi-automated quantitative software by CTA. PMID- 29793848 TI - CAC-DRS: Coronary Artery Calcium Data and Reporting System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT). AB - The goal of CAC-DRS: Coronary Artery Calcium Data and Reporting System is to create a standardized method to communicate findings of CAC scanning on all noncontrast CT scans, irrespective of the indication, in order to facilitate clinical decision-making, with recommendations for subsequent patient management. The CAC-DRS classification is applied on a per-patient basis and represents the total calcium score and the number of involved arteries. General recommendations are provided for further management of patients with different degrees of calcified plaque burden based on CAC-DRS classification. In addition, CAC-DRS will provide a framework of standardization that may benefit quality assurance and tracking patient outcomes with the potential to ultimately result in improved quality of care. PMID- 29793849 TI - Risk of Ischemic Stroke After Perioperative Atrial Fibrillation in Total Knee and Hip Arthroplasty Patients. AB - BACKGROUND: To determine if new-onset perioperative atrial fibrillation during arthroplasty represents a benign response to intraoperative cardiac stress or is a risk factor for stroke, we evaluated the subsequent risk of ischemic stroke in patients with new-onset atrial fibrillation occurring during primary total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Discharge data of all adult patients undergoing primary TKA or THA from 1997 to 2013 were queried via the New York Statewide Planning and Research Cooperative System database to find patients with new-onset perioperative atrial fibrillation. These patients were then followed up over time to determine their risk of ischemic stroke. RESULTS: Of the 312,636 TKA and 215,610 THA unique patient admissions, 3646 (0.7%) had a diagnosis of new-onset perioperative atrial fibrillation. The cohort of patients with this finding was 58.9% female with an average age of 73.6 years and higher prevalence of vascular risk factors. Adjusting for validated stroke risk factors, the risk of ischemic stroke within 1 year after THA or TKA in patients with new-onset atrial fibrillation was 2.7 times higher than in those without a history of atrial fibrillation (odds ratio: 2.7, 95% confidence interval: 1.5-4.8). Hospital length of stay and charges for patients with new onset atrial fibrillation were also greater than patients with either a prior diagnosis or no diagnosis of atrial fibrillation. CONCLUSION: New-onset atrial fibrillation during TKA and THA may indicate risk of ischemic stroke following surgery that should warrant medical follow-up and may increase hospital length of stay and charges. PMID- 29793850 TI - Preoperative Patient Profile in Total Hip and Knee Arthroplasty: Predictive of Increased Medicare Payments in a Bundled Payment Model. AB - BACKGROUND: The shift toward value-based bundled payment models in total joint arthroplasty highlights the need for identification of modifiable risk factors for increased spending as well as opportunities to mitigate perioperative treatment of chronic disease. The purpose of this study was to identify preoperative comorbidities that result in an increased financial burden using institutional data at a single institution. METHODS: We conducted a retrospective review of total joint arthroplasty patients and collected payment data from the Center for Medicare and Medicaid Services for each patient up to 90 days after surgery in accordance with the regulations of the Comprehensive Care for Joint Replacement initiative. Statistical analysis and comparison of preoperative profile and Medicare payments as a surrogate for cost were completed. RESULTS: Six hundred ninety-four patients were identified over a 4-year time period who underwent surgery before adoption of the Comprehensive Care for Joint Replacement but that met criteria for inclusion. The median total payment per patient episode of care was $20,048. Preoperative diagnosis of alcoholism, anemia, diabetes, and obesity was found to have a statistically significant effect on total payments. The model predicted a geometric mean increase from $1425 to $9308 for patients bearing these comorbidities. CONCLUSION: With Medicare payments as a surrogate for cost, we demonstrate that specific patient comorbidities and a cumulative increase in comorbidities predict increased costs. This study was based on institutional data rather than administrative data to gain actionable information on an institutional level and highlight potential flaws in research based on administrative data. PMID- 29793851 TI - Evaluation of Examiner Performance Using a Duplex Ultrasound Simulator. Flow Velocity Measurements in Dialysis Access Fistula Models. AB - We developed a duplex ultrasound simulator for training and assessment of scanning skills. We used the simulator to test examiner performance in the measurement of flow velocities in dialysis access fistulas. Test cases were created from 3-D ultrasound scans of two dialysis access fistulas by reconstructing 3-D blood vessel models and simulating blood flow velocity fields within the lumens. The simulator displays a 2-D B-mode or color Doppler image corresponding to transducer position on a mannequin; a spectral waveform is generated according to Doppler sample volume location and system settings. Examiner performance was assessed by comparing the measured peak systolic velocity (PSV) with the true PSV provided by the computational flow model. The PSV measured by four expert examiners deviated from the true value by 7.8 +/- 6.1%. The results indicate the ability of the simulator to objectively assess an examiner's measurement accuracy in complex vascular targets. PMID- 29793852 TI - Ultrasound-Enhanced Protective Effect of Tetramethylpyrazine via the ROS/HIF-1A Signaling Pathway in an in Vitro Cerebral Ischemia/Reperfusion Injury Model. AB - Reactive oxygen species-induced oxidative stress is an important pathophysiological process during cerebral ischemia/reperfusion (I/R) injury. It has been reported that the protective effect of tetramethylpyrazine (TMP) against cerebral I/R injury can be significantly improved by its combination with ultrasound exposure. However, the molecular mechanisms and signaling pathways underlying the synergistic protective effect remain unclear. In the present work, the damage induced by I/R injury was modeled by glutamate-induced toxicity to pheochromocytoma (PC12) cells. The ultrasound-enhanced protective effect of TMP was systemically investigated by measuring variations in cell viability, cell migration and levels of intracellular reactive oxygen species, the oxidative stress-related protein glutathione, apoptosis-related proteins (caspase-8, -9 and -3), as well as expression of related genes (hypoxia-inducible factor-1a, p53, murine double minute2). The results suggest that the ultrasound-enhanced protective effect of TMP against cerebral I/R injury might act via the reactive oxygen species/hypoxia-inducible factor-1a signaling pathway, and an appropriate ultrasound intensity should be selected to achieve an optimal synergistic neuroprotective effect. PMID- 29793853 TI - Superselective Drug Delivery Using Doxorubicin-Encapsulated Liposomes and Ultrasound in a Mouse Model of Lung Metastasis Activation. AB - Conventional treatment of lymph node metastasis involves dissection of the tumor and regional lymph nodes, but this may cause activation of latent metastatic tumor cells. However, there are few reports on animal models regarding the activation of latent metastatic tumor cells and effective methods of treating activated tumor cells. Here, we report the use of a superselective drug delivery system in a mouse model of lung metastasis in which activated tumor cells are treated with doxorubicin-encapsulated liposomes (DOX-LP) and ultrasound. The axillary lymph node was injected with DOX-LP and exposed to ultrasound so that the released DOX would be delivered from the axillary lymph node to the metastatic lung via the subclavian vein, heart and pulmonary artery. The size of the DOX-LP was optimized to a diameter of 460 nm using indocyanine green encapsulated liposomes, and the ultrasound intensity was 0.5 W/cm2. We found that compared with DOX or DOX-LP alone, the superselective drug delivery system was effective in the treatment of metastasis in both the lung and axillary lymph node. We anticipate that this superselective drug delivery system will be a starting point for the development of new techniques for treating lung metastasis in the clinical setting. Furthermore, the superselective drug delivery system may be used to screen novel drugs for the treatment of lung cancer and investigate the mechanisms of tumor cell activation after resection of a primary tumor or lymph nodes. PMID- 29793854 TI - Scaphoid-trapezium hereditary coalition. A case report. AB - Carpal coalitions are relatively frequent between bones in the same carpal row. Coalitions between bones of different rows, however, are very uncommon. We present a case of bilateral intercarpal coalition between the trapezium and scaphoid as an incidental finding, confirming its hereditary origin since a parent has the same bilateral coalition. PMID- 29793855 TI - Cost of osteoporotic hip fracture in Spain per Autonomous Region. AB - OBJECTIVE: We estimated the health resource utilization (HRU) and associated costs during the 12months after a first osteoporotic hip fracture (OHF) in six Spanish Regions. METHODS: Observational, prospective study including patients >=65years-old hospitalized due to a first OHF in: Andalusia, Catalonia, Valencian Community, Galicia, Madrid and the Basque Country. HRU related to OHF, quality of life and patient autonomy were collected, and HRU-associated costs were estimated. RESULTS: Four hundred and eighty-seven patients (mean age: 83.1years, 77% women) were included, with demographic characteristics that were similar across the Regions. Mean hospital stay was longest in Madrid and Galicia (women/men: 15.0/18.6 and 16.9/12.6days, respectively) and shortest in Andalusia and the Valencian Community (8.2/7.2 and 8.4/9.4days). There were more rehabilitation sessions and formal home care days in Catalonia and Madrid (women/men: 16/21 and 17/29 sessions; 19/20 and 30/27days) and fewer in Andalusia and Galicia (4/1 and 3/0 sessions; 3/1 and 1/0days). Mean HRU costs were higher in Madrid and lower in Andalusia (women/men: 12,321?/12,297? and 7,031?/6,115?, respectively). CONCLUSIONS: OHF place a large burden on Spanish Regional Health Systems, including high economic costs. We found notable differences in mean costs across the Regions, mainly caused by the differential length of the first hospital stay and the outpatient care in subsequent months. These differences may be associated with differences in surgical delay. A national consensus on the management of OHF is desirable; moreover, agreeing common guidelines could have major socio-economic and healthcare benefits. PMID- 29793856 TI - The anti-inflammatory properties of tiotropium. PMID- 29793858 TI - Tralokinumab unsuccessful for management of severe, uncontrolled asthma. PMID- 29793859 TI - COPD awareness and treatment in China. PMID- 29793860 TI - Outdoor air pollution and cystic fibrosis. AB - Outdoor air pollution is increasingly identified as a contributor to respiratory and cardiovascular disease. Pro-inflammatory particles and gases are inhaled deep into the lungs, and are associated with impaired lung growth and exacerbations of chronic respiratory diseases. The magnitude of these effects are of interest to patients and families, and have been assessed in studies specific to CF. Using systematic review methodology, we sought to collate these studies in order to summarise the known effects of air pollution in cystic fibrosis, and to present information on decreasing personal air pollution exposures. PMID- 29793857 TI - Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. AB - BACKGROUND: The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 15 centres across the UK, Denmark, and Canada. We enrolled participants of either sex aged 18-75 years with inadequately controlled moderate-to-severe asthma for 12 months or more, requiring treatment with inhaled corticosteroids at a stable dose. We randomly assigned participants (1:1) to receive tralokinumab (300 mg) or placebo by an interactive web-based system or voice response system. Participants and study personnel were masked to treatment allocation. Both tralokinumab and placebo were administered subcutaneously every 2 weeks. The primary outcome measure was change from baseline to week 12 in bronchial biopsy eosinophil count. Secondary outcome measures included change in blood and sputum eosinophil counts. Exploratory outcomes included fractional exhaled nitric oxide (FENO) and blood IgE concentrations. Safety analyses were carried out in all participants who received study drug. This trial is registered with ClinicalTrials.gov, number NCT02449473, and with the European Clinical Trials Database, EudraCT 2015-000857 19. FINDINGS: Between Sept 25, 2015, and June 21, 2017, 224 participants were enrolled and screened. Of these participants, 79 were randomly assigned to receive tralokinumab (n=39) or placebo (n=40). Tralokinumab did not significantly affect bronchial eosinophil count compared with placebo at week 12 (treatment effect ratio 1.43, 95% CI 0.63-3.27; p=0.39). Compared with placebo, tralokinumab did not significantly affect blood eosinophil count (treatment effect ratio 1.21, 95% CI 1.00-1.48; p=0.055) or sputum eosinophil count (0.57, 0.06-6.00; p=0.63), but FENO concentration (0.78, 0.63-0.96; p=0.023) and total blood IgE concentration (0.86, 0.77-0.97; p=0.014) were significantly reduced. 33 (85%) of 39 patients receiving tralokinumab and 32 (80%) of 40 receiving placebo reported at least one adverse event during the treatment period. No deaths in either treatment group were observed. Treatment-related adverse events occurred more frequently in the tralokinumab group than in the placebo group (11 [28%] of 39 vs seven [18%] of 40). INTERPRETATION: Tralokinumab did not significantly affect eosinophilic inflammation in bronchial submucosa, blood, or sputum compared with placebo, but did reduce FENO and IgE concentrations. These results suggest interleukin 13 is not crucial for eosinophilic airway inflammation control in moderate-to-severe asthma. FUNDING: AstraZeneca. PMID- 29793861 TI - Critical care nurses' knowledge of alarm fatigue and practices towards alarms: A multicentre study. AB - OBJECTIVES: To determine critical care nurses' knowledge of alarm fatigue and practices toward alarms in critical care settings. RESEARCH METHODOLOGY/DESIGN: A cross-sectional survey using an adaptation of The Health Technology Foundation Clinical Alarms Survey. SETTING: A sample of critical care nurses (n = 250) from 10 departments across six hospitals in Ireland. RESULTS: A response rate of 66% (n = 166) was achieved. All hospital sites reported patient adverse events related to clinical alarms. The majority of nurses (52%, n = 86) did not know or were unsure, how to prevent alarm fatigue. Most nurses (90%, n = 148) agreed that non-actionable alarms occurred frequently, disrupted patient care (91%, n = 145) and reduced trust in alarms prompting nurses to sometimes disable alarms (81%, n = 132). Nurses claiming to know how to prevent alarm fatigue stated they customised patient alarm parameters frequently (p = 0.037). Frequent false alarms causing reduced attention or response to alarms ranked the number one obstacle to effective alarm management; this was followed by inadequate staff to respond to alarms. Only 31% (n = 50) believed that alarm management policies and procedures were used effectively. CONCLUSION: Alarm fatigue has the potential for serious consequences for patient safety and answering numerous alarms drains nursing resources. PMID- 29793862 TI - Protein kinase C-dependent cell damage by unsaturated carbonyl compounds in vascular cells. AB - Unsaturated carbonyl compounds, such as acrolein (ACR) and methyl vinyl ketone (MVK), are known as the environmental pollutants, and are contained in smoke, automobile exhaust, and heated oil. Although they can enter the circulation through the alveolar epithelium, the details of their effects on the vascular system remain to be clarified. We have recently reported that ACR and MVK induce protein kinase C (PKC) activation and cell damage mediated by intracellular Ca2+ in rat glioma cells (Higashi et al., J. Biosci. Bioeng., 124, 680-684, 2017). In this study, we have attempted to elucidate the effects of ACR and MVK on the vascular system, because blood vessels are easily exposed to these compounds. The rat aorta smooth muscle cells A7r5 were highly sensitive to ACR and MVK, whereas the human umbilical vein endothelial cells EA.hy926 were resistant to them. The ACR- and MVK-induced cell damage in A7r5 cells was PKC-dependent. In A7r5 cells, PKCalpha, PKCdelta, PKCepsilon, and PKCiota were expressed. ACR and MVK induced PKCalpha and PKCdelta translocation to the cell membrane. PKC activity was enhanced in A7r5 cells by ACR and MVK. These results indicate that the unsaturated carbonyl compounds might affect the vascular system by damaging smooth muscle cells via PKC activation. PMID- 29793863 TI - Production of giant unilamellar vesicles by the water-in-oil emulsion-transfer method without high internal concentrations of sugars. AB - Giant unilamellar vesicles (GUVs) are large vesicles bounded by a single lipid bilayer, which have been used in various applications as artificial, cell-like compartments. The water-in-oil (w/o) emulsion-transfer method has been attracting attention as a method to prepare GUVs that can efficiently encapsulate macromolecules. For efficient GUV production by this method, non-physiological, high concentrations of sugars are usually required in the inner solution of the GUVs. These sugars limit the utility of the GUVs for a wide range of applications. In this study, we investigated various compositions of the inner and outer solutions to achieve efficient production without high concentrations of sugars through the w/o emulsion-transfer method. Firstly, we adjusted the osmotic pressure and density of the outer solution with NaCl and succeeded in increasing the proportion of GUVs and the absolute number in the prepared liposome population. Secondly, we increased the density of the inner solution with cytochrome c, but the proportion of GUVs and absolute number of vesicles did not increase. Thirdly, we increased the density of the inner and outer solutions with glycerol, which is membrane permeable and can be removed from GUVs, and succeeded in increasing the GUV proportion. These results provide useful information for the efficient preparation of GUVs that enclose a physiologically relevant environment by the w/o emulsion-transfer method. PMID- 29793864 TI - The use of consumer depth cameras for 3D surface imaging of people with obesity: A feasibility study. AB - OBJECTIVE: Three dimensional (3D) surface imaging is a viable alternative to traditional body morphology measures, but the feasibility of using this technique with people with obesity has not been fully established. Therefore, the aim of this study was to investigate the validity, repeatability and acceptability of a consumer depth camera 3D surface imaging system in imaging people with obesity. METHODS: The concurrent validity of the depth camera based system was investigated by comparing measures of mid-trunk volume to a gold-standard. The repeatability and acceptability of the depth camera system was assessed in people with obesity at a clinic. RESULTS: There was evidence of a fixed systematic difference between the depth camera system and the gold standard but excellent correlation between volume estimates (r2=0.997), with little evidence of proportional bias. The depth camera system was highly repeatable - low typical error (0.192L), high intraclass correlation coefficient (>0.999) and low technical error of measurement (0.64%). Depth camera based 3D surface imaging was also acceptable to people with obesity. CONCLUSION: It is feasible (valid, repeatable and acceptable) to use a low cost, flexible 3D surface imaging system to monitor the body size and shape of people with obesity in a clinical setting. PMID- 29793865 TI - The measurement equivalence of a safety climate measure across five faultlines. AB - This study examines the appropriateness of comparing safety climate survey responses across multiple faultlines-hypothetical dividing lines that split a group into subgroups based on one or more attributes. Using survey data from 8790 employees of a multinational chemical processing and manufacturing company from 76 work sites nested within 19 different countries, we examined the multilevel measurement equivalence of a safety climate measure across cultural dimensions, survey languages, organizational hierarchy, employment arrangements, and work environments. As simulation studies support the faultline at the individual-level requires measurement equivalence tests that are different from the faultline at the country-level, we used multi-group multilevel confirmatory factor analyses for the Level-3 faultline, and multilevel factor mixture models for known classes for the Level-1 faultlines. The results demonstrated that faultlines can prevent safety climate measurement equivalence, which prohibits the aggregation of individual-level scores to higher levels and making comparisons across faultlines. This first study on multilevel safety climate measurement equivalence serves as both a warning to safety climate researchers and practitioners regarding the importance of faultlines and reminds us to consider the level of the faultlines when testing measurement equivalence with multilevel data. PMID- 29793866 TI - The impact of texting on driver behaviour at rail level crossings. AB - A driver text messaging in the vicinity of a rail level crossing represents the merging of a high-risk, high-workload driving environment with a highly distracting secondary task. In this simulator study, we examined how texting impacts driver behaviour on approach to actively controlled urban rail level crossings. Twenty-eight participants drove a series of simulated urban routes containing rail level crossings, while sending text messages and while driving without performing a secondary task. At half of the crossings, drivers were required to respond to the crossing warnings as a train approached. Results revealed that texting on approach to rail level crossings had a detrimental impact on a range of driver behaviour measures. Specifically, texting more than doubled the amount of time spent with eyes off the forward roadway, resulting in drivers spending more than half of their approach time to rail level crossings looking away from the road. This lack of visual attention to the roadway was associated with a range of decrements in driving that may be indicative of a loss of situation awareness, including increased brake reaction time to the crossing warnings and a reduction in lateral position control. The findings have safety implications, not only for urban level crossings, but also for passive level crossings where no warnings are present to re-orient the distracted driver's attention toward an approaching train. PMID- 29793867 TI - Heart Rate, Responsiveness to Intravenous Immunoglobulin, and Coronary Artery Aneurysms in Kawasaki Disease. AB - OBJECTIVE: To evaluate whether heart rate (HR) was associated with intravenous immunoglobulin (IVIG) responsiveness or development of coronary artery lesions (CALs) in patients with Kawasaki disease. STUDY DESIGN: We conducted a retrospective cohort study using data from in patients with Kawasaki disease who were hospitalized in our institution from 2006 to 2016. The patients were divided into 5 groups according to the age- and temperature-adjusted HR z score (HRZage/temp) just before IVIG administration. The ORs of outcomes were estimated by using logistic regression models, with the middle group set as the reference. RESULTS: Of the 322 patients, a total of 98 patients (30%) were refractory to initial IVIG treatment. The patients whose HRZage/temp belonged to the lowest group were at the highest risk of being refractory to the initial IVIG treatment (OR 2.10 [95% CI 1.01-4.37]). Multivariable analyses showed the same trend, though this was not statistically significant. The patients with the highest HRZage/temp were most likely to develop CALs (OR 2.61 [95%CI 0.86-7.92]). CONCLUSIONS: In patients with Kawasaki disease , HRs has a different relationship with IVIG responsiveness and CALs. Low HRZage/temp might be associated with high risk of being refractory to the initial IVIG treatment, while the risk of developing CALs increased among those whose HRs were high. Further studies are necessary to investigate the mechanisms regarding HR and these outcomes in Kawasaki disease. PMID- 29793868 TI - Lower Distending Pressure Improves Respiratory Mechanics in Congenital Diaphragmatic Hernia Complicated by Persistent Pulmonary Hypertension. AB - OBJECTIVE: To investigate the effects of distending pressures on respiratory mechanics and pulmonary circulation in newborn infants with congenital diaphragmatic hernia (CDH) and persistent pulmonary hypertension (PPHN). STUDY DESIGN: In total, 17 consecutive infants of >=37 weeks of gestational age with CDH and PPHN were included in this prospective, randomized, crossover pilot study. Infants were assigned randomly to receive 2 or 5 cmH2O of positive end expiratory pressure (PEEP) for 1 hour in a crossover design. The difference between peak inspiratory pressure and PEEP was kept constant. Respiratory mechanics, lung function, and hemodynamic variables assessed by Doppler echocardiography were measured after each study period. RESULTS: At 2 cmH2O of PEEP, tidal volume and minute ventilation were greater (P < .05), and respiratory system compliance was 30% greater (P < .05) than at 5 cmH2O. PaCO2 and ventilation index were lower at 2 cmH2O than at 5 cmH2O (P < .05). Although preductal peripheral oxygen saturation was similar at both PEEP levels, postductal peripheral oxygen saturation was lower (median [range]: 81% [65-95] vs 91% [71-100]) and fraction of inspired oxygen was greater (35% [21-70] vs 25% [21 60]) at 5 cmH2O. End-diastolic left ventricle diameter, left atrium/aortic root ratio, and pulmonary blood flow velocities in the left pulmonary artery were lower at 5 cmH2O. CONCLUSIONS: After surgical repair, lower distending pressures result in better respiratory mechanics in infants with mild-to-moderate CDH. We speculate that hypoplastic lungs in CDH are prone to overdistension, with poor tolerance to elevation of distending pressure. PMID- 29793870 TI - Cell Count Analysis from Nonbronchoscopic Bronchoalveolar Lavage in Preterm Infants. AB - OBJECTIVES: To establish the reference values, diagnostic accuracy, and effect of various factors on cell count in intubated preterm neonates subjected to nonbronchoscopic bronchoalveolar lavage. STUDY DESIGN: This prospective, cross sectional, blinded study included preterm neonates ventilated for any reason who underwent nonbronchoscopic bronchoalveolar lavage if they had not previously received postnatal antibiotics or steroids. Lavage was performed before surfactant replacement, if any. A gentle ventilation policy was applied. Pneumonia was diagnosed using clinical criteria, without considering cell count. Investigators performing cell counts were blinded to the clinical data. RESULTS: There were 276 neonates enrolled; 36 had congenital or ventilator-associated pneumonia. In the 240 noninfected babies, median neutrophil count increased significantly after the first 2 days of ventilation (day 1, 2 cells per field [IQR, 0.0-9.5 cells per field]; day 2, 2 cells per field [IQR, 0-15 cells per field]; day 3, 20 cells per field [IQR, 2-99 cells per field]; day 4, 15 cells per field [IQR, 2-96 cells per field]; P < .0001). No significant difference was seen over time in infected babies. Multivariate analysis indicated pneumonia (standardized beta = 0.134; P = .033) and the time spent under mechanical ventilation before nonbronchoscopic bronchoalveolar lavage as factors significantly influencing neutrophil count (standardized beta = 0.143; P = .027). Neutrophil count was correlated with the duration of ventilation (rho = 0.28; P <.001). Neutrophil counts were higher in infected (24 cells/field [IQR, 5-78] cells/field) than in noninfected babies (4 cells/field [IQR, 1-24 cells/field]; P <.001) and had an moderate reliability for pneumonia within the first 2 days of ventilation (area under the curve, 0.745; (95% CI, 0.672-0.810; P = .002). CONCLUSIONS: We provide reference values for airway neutrophil counts in ventilated preterm neonates. Bronchoalveolar lavage neutrophils significantly increase after 2 days of ventilation. Neutrophil count has moderate accuracy to diagnose pneumonia, but only within the first 2 days of ventilation. PMID- 29793871 TI - Transition Home Plus Program Reduces Medicaid Spending and Health Care Use for High-Risk Infants Admitted to the Neonatal Intensive Care Unit for 5 or More Days. AB - OBJECTIVE: To evaluate the effects of a transition home intervention on total Medicaid spending, emergency department visits, and unplanned readmissions for preterm infants born at <=366/7 weeks gestation and high-risk full-term infants. STUDY DESIGN: The Transition Home Plus (THP) program incorporated enhanced support services before and after discharge from the neonatal intensive care unit (NICU) provided by social workers and family resource specialists (trained peers) working with the medical team from October 2012 to October 2014. Rhode Island Medicaid claims data were used to study the 321 infants cared for in the NICU for >=5 days, who were enrolled in the THP program. THP infants were compared with a historical comparison group of 365 high-risk infants born and admitted to the same NICU in 2011 before the full launch of the THP program. Intervention and comparison group outcomes were compared in the eight 3-month quarters after the infant's birth. Propensity score weights were applied in regression models to balance demographic characteristics between groups. RESULTS: Infants in the intervention group had significantly lower total Medicaid spending, fewer emergency department visits, and fewer readmissions than the comparison group. Medicaid spending savings for the intervention group were $4591 per infant per quarter in our study period. CONCLUSIONS: Transition home support services for high-risk infants provided both in the NICU and for 90 days after discharge by social workers and family resource specialists working with the medical team can reduce Medicaid spending and health care use. PMID- 29793872 TI - A Pediatric Neurology Perspective on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection and Pediatric Acute-Onset Neuropsychiatric Syndrome. PMID- 29793873 TI - Executive summary of the GeSIDA consensus document on control and monitoring of HIV-infected patients. AB - The continuous increase in our knowledge of HIV medicine and antiretroviral treatment has led us to draft specific consensus documents focused on topics other than antiretroviral therapy, such as treatment of opportunistic diseases, pre- and post-exposure prophylaxis, metabolic abnormalities, treatment of HBV or HCV coinfection, treatment of patients coinfected with tuberculosis, osteoporosis, kidney disorders, and cardiovascular risk. Accordingly, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology has promoted the drafting of this consensus document on the control and monitoring of adult patients infected with HIV. The document provides recommendations on the initial evaluation and subsequent monitoring of HIV infected patients that will prove useful for all professionals involved in the management of this infection. PMID- 29793874 TI - Validity and Reliability Study of Bahasa Malaysia Version of Voice Handicap Index 10. AB - OBJECTIVES: This study aimed to determine the validity and reliability of Bahasa Malaysia version of Voice Handicap Index-10 (mVHI-10). MATERIALS AND METHODS: This cross-sectional study was carried out in the Otorhinolaryngology, Head and Neck Surgery Department of Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from June 2015 to May 2016. The mVHI-10 was produced following a rigorous forward and backward translation. One hundred participants, including 50 healthy volunteers (17 male, 33 female) and 50 patients with voice disorders (26 male, 24 female), were recruited to complete the mVHI-10 before flexible laryngoscopic examinations and acoustic analysis. The mVHI-10 was repeated in 2 weeks via telephone interview or clinic visit. Its reliability and validity were assessed using interclass correlation. RESULTS: The test-retest reliability for total mVHI 10 and each item score was high, with the Cronbach alpha of >0.90. The total mVHI 10 score and domain scores were significantly higher (P < 0.001) in the pathology groups (20.92 +/- 8.74) than healthy volunteers (1.54 +/- 1.97), depicting excellent discriminant validity. The Kaiser-Meyer-Olkin measure was 0.92, which depicted excellent construct validity. There was a significant positive correlation between the mVHI-10 score and jitter and shimmer result (P < 0.001). CONCLUSIONS: The present study showed good reliability and validity of the mVHI 10 when applied to both healthy volunteers and patients with voice disorders. We recommend the use of the mVHI-10 in daily clinical practice among Bahasa Malaysia speaking population. PMID- 29793875 TI - The Developing Female Chorister Voice: Case-Study Evidence of Musical Development. AB - The human singing voice changes throughout the lifespan and there are gender specific variations that need to be taken into account. Life changes in terms of voice are different for females and males and this paper concentrates on the female singing voice in the context of choral singing. Case-study data from three choristers are presented relating to the changing female voice during puberty as part of a longitudinal study of female choristers in a major English Cathedral Choir School. In addition, discussion is presented on important considerations with respect to the female choral singing voice with a particular focus on specific choral aspects during rehearsals and performance. PMID- 29793876 TI - Effectiveness of Vocal Therapy for the Elderly When Applying Conventional and Intensive Approaches: A Randomized Clinical Trial. AB - OBJECTIVES: The aim of this study was to verify the effects of the method Vocal Therapy for the Elderly and the differences in treatment efficacy when it was administered intensively or in the conventional way. METHODS: Twenty-seven elderly individuals were randomized into two groups and referred for 16 sessions of vocal therapy. The Intensive Group (IG) had therapy four times a week, whereas the Conventional Group had it twice a week. The effects of the therapy were assessed by auditory-perceptual analysis, the Voice-Related Quality of Life protocol, and visual-perceptive analysis of laryngoscopy examinations. The first stage consisted of evaluating the vocal quality and self-assessment of 15 subjects before and after a time period equal to that which they would undergo in vocal therapy. The second stage consisted of comparing the assessments of all participants in the week preceding the beginning of treatment, in the week following the end of treatment, and 1 month after that. RESULTS: There was no difference between perceptual voice parameters and self-assessment when the subjects were not undergoing therapy. When comparing the periods immediately before and after therapy, there was improvement in vocal quality and Voice Related Quality of Life. One month later, the benefits that had been revealed through the self-assessment protocol, and some of the improvements in vocal parameters were maintained. There was no difference between the IG and Conventional Group with the exception of vocal fold bowing, which decreased in the IG group. CONCLUSIONS: The Vocal Therapy for the Elderly program is effective for treating voice presbyphonia. An intensive approach may be superior with regard to vocal fold bowing. PMID- 29793879 TI - Management of Neonatal Abstinence Syndrome: The Importance of a Multifaceted Program Spanning Inpatient and Outpatient Care. PMID- 29793880 TI - Early Treatment Innovation for Opioid-Dependent Newborns: A Retrospective Comparison of Outcomes, Utilization, Quality, and Safety, 2006-2014. AB - BACKGROUND: Few coordinated treatment programs address the needs of infants and families struggling with the effects of substance use. In 2003 a large Southeastern regional hospital launched the Managing Abstinence in Newborns (MAiN) program, providing multidisciplinary, coordinated, community-based care for neonatal abstinence syndrome (NAS). A hypothesis-generating study was conducted to compare the outcomes of MAiN infants to comparable NAS infants receiving traditional care from 2006 through 2014 in South Carolina. METHODS: De identified sociodemographic and clinical data on MAiN infants, as well as NAS infants not treated with MAiN, were obtained from South Carolina statewide databases. Study measures included medical and safety outcomes, health services utilization, child protective services involvement, emergency services utilization, and inpatient readmissions. RESULTS: Some 110 infants were identified who received the MAiN intervention and 356 NAS infants, also in South Carolina, who were potentially MAiN eligible. Overall, there were no significant differences in the two groups regarding medical or safety outcomes or child protective services involvement. Traditional care NAS infants were more likely to be treated in a higher-level nursery (68.8% vs. 0%). MAiN infants had $8,204 less per birth in median charges (p <0.001) than the traditional care NAS infants. MAiN infants also had a lower percentage of ED visits (p = 0.01) assessed as possibly or likely NAS related compared to traditional care NAS infants. CONCLUSION: This study demonstrates the potential value of implementing the MAiN model in eligible NAS infants. With no difference in medical and safety outcomes and a significant reduction in charges, the MAiN model can be considered safe and cost-effective. PMID- 29793877 TI - Comparative effectiveness of bariatric procedures among adolescents: the PCORnet bariatric study. AB - BACKGROUND: Bariatric surgery has been used for treatment of severe obesity in adolescents but most studies have been small and limited in follow-up. OBJECTIVES: We hypothesized that electronic health record data could be used to compare effectiveness of bariatric procedures in adolescents. SETTING: Data were obtained from clinical research networks using a common data model to extract data from each site. METHODS: Adolescents who underwent a primary bariatric procedure from 2005 through 2015 were identified. The percent change in body mass index (BMI) at 1, 3, and 5 years was estimated using random effects linear regression for patients undergoing all operations. Propensity score adjusted estimates and 95% confidence intervals were estimated for procedures with >25 patients at each time period. RESULTS: This cohort of 544 adolescents was predominantly female (79%) and White (66%), with mean (+/-standard deviation) age of 17.3 (+/-1.6) years and mean BMI of 49.8 (+/- 7.8) kg/m2. Procedures included Roux-en-Y gastric bypass (RYGB; n = 177), sleeve gastrectomy (SG; n = 306), and laparoscopic adjustable gastric banding (n = 61). For those undergoing RYGB, SG, and laparoscopic adjustable gastric banding, mean (95% confidence interval) BMI changes of -31% (-30% to -33%), -28% (-27% to -29%), and -10% (-8% to -12%), were estimated at 1 year. For RYGB and SG, BMI changes of -29% (-26% to -33%) and -25% (-22% to -28%) were estimated at 3 years. CONCLUSIONS: Adolescents undergoing SG and RYGB experienced greater declines in BMI at 1- and 3-year follow-up time points, while laparoscopic adjustable gastric banding was significantly less effective for BMI reduction. PMID- 29793878 TI - TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma. AB - TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied. In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastatic melanoma by analyzing the data from one public cohort consisting of 110 patients with metastatic melanoma. The sequencing, mRNA and survival data of 368 patients with skin melanoma from The Cancer Genome Atlas (TCGA) was used to explore the underlying mechanism. TP53 mutation was associated with significant poorer progression-free survival (HR, 2.25; 95% CI, 1.15-4.37; P = 0.014), poorer overall survival (HR, 2.05; 95% CI, 1.02-4.13; P = 0.040) and trend of poorer response (OR, 0.20; 95% CI, 0.02-1.62; P = 0.131). The correlations were significant in multivariate analysis including lactate dehydrogenase, tumor mutational burden and tumor stage (P < 0.05). In TCGA, no association was observed between TP53 mutation and survival (P = 0.55). The mRNA expression of FAS was lower in patients with TP53 mutation than TP53 wild-type. Our findings suggest that TP53 mutation is a potential negative predictor of metastatic melanoma treated with CTLA-4 blockade. PMID- 29793882 TI - Using an Inpatient Quality Improvement Curriculum for Internal Medicine Residents to Improve Pneumococcal Conjugate Vaccine Administration Rates. AB - BACKGROUND: Pneumococcal infections are an important source of morbidity and mortality in older adults and persons with compromised immune systems. New recommendations from the Advisory Committee on Immunization Practices (ACIP) became available September 2014, which included recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13). A study was conducted to increase the PCV13 vaccination rates of hospitalized patients at the White River Junction Veterans Affairs Medical Center (White River Junction, Vermont) through the use of a resident-driven quality improvement (QI) project. METHODS: From December 2014 through April 2016, 16 internal medicine inpatient residents addressed inpatient PCV13 vaccination rates by participating in the facility's QI curriculum. Eight Plan-Do-Study-Act cycles were used, including discharge template editing, electronic reminders, and the discovery of a vaccination administration documentation error in the record through data validation. The measure was the monthly percentage of patients who received PCV13 vaccination (vaccination completion rate) of those discharged from the hospital medicine service who were due for PCV13 vaccination. RESULTS: The percentage of veterans discharged with an up-to-date PCV13 vaccination on discharge increased from approximately 30% to 87% and was sustained. CONCLUSION: Despite being driven by many different residents, this project demonstrates that continuous improvement can be achieved through a structured and iterative process while providing active learning of core QI concepts to residents. It also displays a method in which new guidelines can be incorporated into practice in an effective manner. Finally, this project is an example of how resident-driven data validation can lead to further improvement. PMID- 29793881 TI - Using Concentration Curves to Assess Organization-Specific Relationships between Surgeon Volumes and Outcomes. AB - BACKGROUND: A well-documented association exists between higher surgeon volumes and better outcomes for many procedures, but surgeons may be reluctant to change practice patterns without objective, credible, and near real-time data on their performance. In addition, published thresholds for procedure volumes may be biased or perceived as arbitrary; typical reports compare surgeons grouped into discrete procedure volume categories, even though the volume-outcomes relationship is likely continuous. METHODS: The concentration curves methodology, which has been used to analyze whether health outcomes vary with socioeconomic status, was adapted to explore the association between procedure volume and outcomes as a continuous relationship so that data for all surgeons within a health care organization could be included. Using widely available software and requiring minimal analytic expertise, this approach plots cumulative percentages of two variables of interest against each other and assesses the characteristics of the resulting curve. Organization-specific relationships between surgeon volumes and outcomes were examined for three example types of procedures: uncomplicated hysterectomies, infant circumcisions, and total thyroidectomies. The concentration index was used to assess whether outcomes were equally distributed unrelated to volumes. RESULTS: For all three procedures, the concentration curve methodology identified associations between surgeon procedure volumes and selected outcomes that were specific to the organization. The concentration indices confirmed the higher prevalence of examined outcomes among low-volume surgeons. The curves supported organizational discussions about surgical quality. CONCLUSION: Concentration curves require minimal resources to identify organization- and procedure-specific relationships between surgeon procedure volumes and outcomes and can support quality improvement. PMID- 29793883 TI - Reducing Serious Safety Events and Priority Hospital-Acquired Conditions in a Pediatric Hospital with the Implementation of a Patient Safety Program. AB - BACKGROUND: A freestanding children's hospital evaluated the impact of a patient safety program on serious safety events (SSEs) and hospital-acquired conditions (HACs). METHODS: The No Harm Patient Safety Program was developed throughout the organization using a multifaceted approach that included safety moments, leadership rounding, cause analysis changes, event reporting enhancements, error prevention training, leadership training, identifying priority HACs, Eye on Safety Campaign, and safety coaches. The organization set strategic goals for improvement of SSEs and priority HACs. RESULTS: The rate of SSEs decreased from 0.19 in 2014 to 0.09 in 2015. The rate significantly declined from 2015 to 2016 to a rate of 0.00, for a rate difference of -0.00009 (95% confidence interval [CI]: -0.00016, -0.00002; p = 0.012). The organization reached two years without an SSE in July 2017. The central line-associated bloodstream infection rate significantly declined from 2.8 per 1,000 line-days in 2015 to 1.6 in 2016, for a difference of -0.00118 (95% CI: -0.002270, -0.00008; p = 0.036). Surgical site infection rates declined from a 2015 rate of 3.8 infections per 100 procedures to a 2016 rate of 2.6 (p = 0.2962), and catheter-associated urinary tract infection rates declined from a 2015 rate of 2.7 per 1,000 catheter-days to a 2016 rate of 1.4 (p = 0.2770). CONCLUSION: The No Harm Patient Safety Program was interwoven into the organization's strategic mission and values, and key messaging was used to purposefully tie the many interventions being implemented back to it. These interventions were associated with improvements in patient safety outcomes. PMID- 29793884 TI - What is the Realistic Scope of Informed Consent? PMID- 29793885 TI - Opportunities to Improve Informed Consent with AHRQ Training Modules. AB - BACKGROUND: Informed consent is a process of communication between clinician and patient that results in the patient's decision about whether to undergo a specific intervention. However, patients often do not understand the risks, benefits, and alternatives, even after signing a consent form. METHODS: Mixed methods pilot test of two Agency for Healthcare Research and Quality (AHRQ) informed consent training modules implemented in four hospitals. Methods included staff and patient surveys, interviews, site visits, and pre- and posttests of the modules. RESULTS: A low proportion of clinicians reported using teach-back (40.0%) or high-quality decision aids (55.0%). Patients reported limited use of best practices, including being asked to teach-back (58.4%), having other options described (54.9%), viewing decision aids (37.4%), and finding the form very easy to understand (66.8%). Content of the training modules aligned well with identified deficiencies. Barriers to completing the modules included staff turnover, competing demands, and lack of accountability. Facilitators included committed champions with available time, motivation, and release time for staff to take modules. Knowledge increased for leaders (p <0.05) and staff (p <0.001) who completed the training modules. Hospitals reported the effects of piloting the modules included fostering dialogue and identifying opportunities for improvements, identifying and rectifying policy ambiguity and noncompliance, reinforcing the use of interpreter services, and using modules' strategies and tools to improve informed consent. CONCLUSION: Many opportunities exist for hospitals to improve their informed consent practices. AHRQ's two training modules, have face validity, addressed demonstrated deficiencies in hospitals' informed consent policies and processes, and stimulated improvement activity in motivated hospitals. PMID- 29793887 TI - The Characteristics of Physicians Who are Re-Disciplined by Medical Boards: A Retrospective Cohort Study. AB - BACKGROUND: Physician misconduct adversely affects patient safety and is therefore of societal importance. Little work has specifically examined re disciplined physicians. A study was conducted to compare the characteristics of re-disciplined to first-time disciplined physicians. METHODS: A retrospective review of Canadian physicians disciplined by medical boards between 2000 and 2015 was conducted. Physicians were divided into those disciplined once and those disciplined more than once. Differences in demographics, transgressions, and penalties were evaluated. RESULTS: There were 938 disciplinary events for 810 disciplined physicians with 1 in 8 (n = 101, 12.5%) being re-disciplined. Re disciplined physicians had up to six disciplinary events in the study period and 4 (4.0%) had events in more than one jurisdiction. Among those re-disciplined, 94 (93.1%) were male, 34 (33.7%) were international medical graduates, and 88 (87.1%) practiced family medicine (n = 59, 58.4%), psychiatry (n = 11, 10.9%), surgery (n = 9, 8.9%), or obstetrics/gynecology (n = 9, 8.9%). The proportion of obstetrician/gynecologists was higher among re-disciplined physicians (8.9% vs. 4.2%, p = 0.048). Re-disciplined physicians had more mental illness (1.7% vs. 0.1%, p = 0.01), unlicensed activity (19.2% vs. 7.2%, p <0.01), and less sexual misconduct (20.1% vs. 27.9%, p = 0.02). License suspension occurred more frequently among those re-disciplined (56.8% vs. 48.0%, p = 0.02) as did license restriction (38.4% vs. 26.7%, p <0.01). License revocation was not different between cohorts (10.9% vs. 13.5%, p = 0.36). CONCLUSION: Re-discipline is not uncommon and underscores the need for better identification of at-risk individuals and optimization of remediation and penalties. The distribution of transgression argues for a national disciplinary database that could improve communication between jurisdictional medical boards. PMID- 29793886 TI - Implementation and Evaluation of a Novel Colorectal Cancer Decision Aid Using a Centralized Delivery Strategy. AB - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States; however, CRC screening reduces both incidence and mortality rates. Patient decision aids (DAs) are an evidence-based strategy to support patients making health-related decisions. CRC screening DAs can be unsuccessful due to provider preferences for colonoscopy and lack of effective DA implementation strategies within clinical settings. METHODS: A hybrid implementation-effectiveness study was conducted testing the feasibility of using an existing centralized preventive health screening outreach infrastructure to implement a novel CRC DA across a health care system. Participants included primary care patients at one of three study clinics. Implementation was assessed by determining whether patients remembered receiving the DA and were aware of CRC screening options. Effectiveness was measured by comparing overall screening rates between the control and intervention groups. RESULTS: Using a centralized delivery system was a feasible and efficient method for implementing DAs to a large academic health system. More than 90% of the intervention group remembered receiving the DA, and 80% found it helpful in their decision-making process. The DA was successful in improving CRC screening knowledge; however, overall CRC screening rates significantly decreased between the control and intervention periods (50.8% vs. 39.2%, respectively; p = 0.03). CONCLUSION: Centralized delivery is a feasible method for DA implementation. Although DAs increase knowledge, the true effectiveness of CRC DAs in clinical settings is unknown, as a result of the number in screening tests, diversity in DA format, and the variability in dissemination and implementation practices. PMID- 29793888 TI - Principles of Automation for Patient Safety in Intensive Care: Learning From Aviation. AB - BACKGROUND: The transition away from written documentation and analog methods has opened up the possibility of leveraging data science and analytic techniques to improve health care. In the implementation of data science techniques and methodologies, high-acuity patients in the ICU can particularly benefit. The Principles of Automation for Patient Safety in Intensive Care (PASPIC) framework draws on Billings's principles of human-centered aviation (HCA) automation and helps in identifying the advantages, pitfalls, and unintended consequences of automation in health care. THE FRAMEWORK AND ITS KEY CHARACTERISTICS: Billings's HCA principles are based on the premise that human operators must remain "in command," so that they are continuously informed and actively involved in all aspects of system operations. In addition, automated systems need to be predictable, simple to train, to learn, and to operate, and must be able to monitor the human operators, and every intelligent system element must know the intent of other intelligent system elements. In applying Billings's HCA principles to the ICU setting, PAPSIC has three key characteristics: (1) integration and better interoperability, (2) multidimensional analysis, and (3) enhanced situation awareness. RECOMMENDATIONS: PAPSIC suggests that health care professionals reduce overreliance on automation and implement "cooperative automation" and that vendors reduce mode errors and embrace interoperability. CONCLUSION: Much can be learned from the aviation industry in automating the ICU. Because it combines "smart" technology with the necessary controls to withstand unintended consequences, PAPSIC could help ensure more informed decision making in the ICU and better patient care. PMID- 29793869 TI - Extreme Preterm Infant Rates of Overweight and Obesity at School Age in the SUPPORT Neuroimaging and Neurodevelopmental Outcomes Cohort. AB - OBJECTIVE: To identify rates of overweight (body mass index [BMI] >=85th percentile) and obesity (BMI >=95th percentile) at 6-7 years of age and associated risk factors among extremely preterm infants born at <28 weeks of gestation. STUDY DESIGN: Anthropometrics, blood pressure, and active and sedentary activity levels were prospectively assessed. Three groups were compared, those with a BMI >=85th percentile (overweight or obese for age, height, and sex) and >=95th percentile (obese) vs <85th percentile. Multiple regression analyses estimated the relative risks of BMI >=85th percentile and >=95th percentile associated with perinatal and early childhood factors. RESULTS: Of 388 children, 22% had a BMI of >=85th percentile and 10% were obese. Children with obesity and overweight compared with normal weight children had higher body fat (subscapular skinfold and triceps skinfold >85th percentile), central fat (waist circumference >90th percentile), spent more time in sedentary activity (20.5 vs 18.2 vs 16.7 hours/week), and had either systolic and/or diastolic hypertension (24% vs 26% vs 14%), respectively. Postdischarge weight gain velocities from 36 weeks postmenstrual age to 18 months, and 18 months to 6-7 years were independently associated with a BMI of >=85th percentile, whereas weight gain velocity from 18 months to 6-7 years was associated with obesity. CONCLUSIONS: One in 5 former extremely preterm infants is overweight or obese and has central obesity at early school age. Postdischarge weight gain velocities were associated with overweight and obesity. These findings suggest the obesity epidemic is spreading to the most extremely preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063 and NCT0000. PMID- 29793889 TI - Effects of Home Mechanical Ventilation on Left Ventricular Function in Sarcoglycanopathies (Limb Girdle Muscular Dystrophies). AB - Cardiac and respiratory function may be impaired in sarcoglycanopathies, a subgroup of muscular dystrophies due to sarcoglycan proteins (alpha, beta, gamma, and delta) genes mutations. Management of patients with restrictive respiratory failure mainly relies on home mechanical ventilation (HMV). Little is known about the cardiac effects of prolonged mechanical ventilation in patients with muscular dystrophy and restrictive respiratory insufficiency. We aimed to assess the effects of HMV on cardiac function in sarcoglycanopathies. We retrospectively included 10 genetically proven patients with sarcoglycanopathy followed at the HMV unit of the Raymond Poincare University Hospital (4 patients with alpha sarcoglycanopathy and 6 patients with gamma-sarcoglycanopathy). We collected cardiorespiratory clinical baseline data and left ventricular ejection fraction (LVEF) at baseline before initiation of HMV and at the end of follow-up. At baseline, median age was 30.5 years (27 to 39) and median pulmonary vital capacity was 27% of the predicted value (21 to 36). Forty percent of the patients had documented sleep apnea. Cardiomyopathy, defined as LVEF <50%, was found in 3 patients with gamma-sarcoglycanopathy. After a median follow-up of 3 years (1.0 to 4.5), there was a significant increase in LVEF after initiation of HMV, that is, 62% (48 to 65) versus 53% (45.5 to 56.5) (p = 0.0039). In conclusion, HMV in sarcoglycanopathies is not harmful and may protect left ventricular function by its thoracic physiological effects. PMID- 29793890 TI - Differential effects of adolescent and adult-initiated voluntary exercise on context and cued fear conditioning. AB - Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated in adolescence, on brain and behaviour in adulthood is not yet fully explored or understood. The aim of this study was to compare the impact of voluntary exercise that was initiated either during adolescence or early adulthood on cognitive performance in hippocampal and amygdala-dependent fear conditioning tasks in adulthood. Adult (eight weeks old) and adolescent (four weeks old) male Sprague Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for seven weeks. Adult-initiated exercise enhanced both contextual and cued fear conditioning, while conversely, exercise that began in adolescence did not affect performance in these tasks. These behaviours were accompanied by differential expression of plasticity related genes in the hippocampus and amygdala in adulthood. Specifically, adolescent-initiated exercise increased the expression of an array of plasticity related genes in the hippocampus including BDNF, synaptophysin, Creb, PSD-95, Arc, TLX and DCX, while adult-initiated exercise did not affect hippocampal plasticity related genes. Together results show that exercise initiated during adolescence has a differential effect on hippocampal and amygdala-dependent behaviour and neuronal plasticity compared to when exercise was initiated in adulthood. These findings reinforce adolescence as a period during which environmental influences have a distinct impact on neuronal plasticity and cognition. PMID- 29793891 TI - Sustained impact of rotavirus vaccine on rotavirus hospitalisations in Lusaka, Zambia, 2009-2016. AB - BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Lusaka in February 2012 and rolled out countrywide in November 2013 in the routine Expanded Programme on Immunisation and administered at 6 and 10 weeks with no catch up dose. Reported here is the monitoring of rotavirus acute gastroenteritis hospitalisations at the University Teaching Hospital, Lusaka, Zambia as part of efforts to document the impact of rotavirus vaccine. METHODS: Children <5 years hospitalised for acute gastroenteritis (AGE) from January 2009 to December 2016 were recruited into the rotavirus disease burden active surveillance and had their stools tested for rotavirus by enzyme immunoassay. We compared rotavirus associated AGE hospitalisations of the pre-vaccine era (2009-2011) with the post rotavirus vaccine introduction period (2013-2016). RESULTS: With the increase in RV1 coverage in Lusaka, rotavirus AGE declined significantly from 40% of diarrhoea hospitalisation in the pre-vaccine era to 29% of diarrhoea hospitalisation in the post-vaccine era (p < 0.001) in children <5 years. After a decreasing trend in rotavirus positivity from 2013 to 2015, positivity increased to 37% in 2016. However, the post-vaccine years (2012-2016) saw substantial decline in the number tested (median decline: 34% (range: 20-43%)) and the number of positive results (median decline: 52% (range: 30-65%). CONCLUSION: A sustained and significant decline in rotavirus AGE hospitalisations was observed in children <5 years since the introduction of RV1 in Lusaka, Zambia. Despite an increase in rotavirus positivity in 2016, the total number of children enrolled and the number of rotavirus positive children remained below baseline. The reason for the increase in rotavirus positivity in 2016 is unknown but could be due to an accumulation of susceptible children and the shifting of disease to children of older age groups. This finding underscores the need for continued monitoring of rotavirus vaccine impact. PMID- 29793892 TI - Assessing population immunity for measles elimination - The promise and peril of serosurveys. PMID- 29793893 TI - Protective immune response against Toxoplasma gondii elicited by a novel yeast based vaccine with microneme protein 16. AB - Toxoplasma gondii is an obligate intracellular protozoan that can invade all eukaryotic cells and infect all warm-blood animals, causing the important zoonosis toxoplasmosis. Invasion of host cells is the key step necessary for T. gondii to complete its life cycle and microneme proteins play an important role in attachment and invasion of host cells. Microneme protein 16 (TgMIC16) is a new protective protein in T. gondii and belongs to transmembrane microneme proteins (TM-MIC). The TM-MICs are released onto the parasite's surface as complexes capable of interacting with host cell receptors. In the present study, we expressed the TgMIC16 protein on the surface of Saccharomyce cerevisiae (pCTCON2 TgMIC16/EBY100) and evaluated it as a potential vaccine for BALB/c mice against challenge infection with the RH strain of T. gondii. We immunized BALB/c mice both orally and intraperitoneally. After three immunizations, the immune response was evaluated by measuring antibody levels, lymphocyte proliferative responses, percentages of CD4+ and CD8+ T lymphocytes, cytokine production, and the survival times of challenged mice. The results showed that the pCTCON2-TgMIC16/EBY100 vaccine stimulated humoral and cellular immune responses. In addition, mice immunized with the pCTCON2-TgMIC16/EBY100 vaccine showed increased survival times compared with non-immunized controls. In summary, TgMIC16 displayed on the cell surface of S. cerevisiae could be used as potential vaccine against toxoplasmosis. PMID- 29793894 TI - An update from hospital-based surveillance for rotavirus gastroenteritis among young children in Bangladesh, July 2012 to June 2017. AB - INTRODUCTION: In preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. METHODS: We enrolled and collected fresh stool from every fourth child < 5 years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. RESULTS: We found that 64% (4832/7562) of children < 5 years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were <12 months of age. The most common strains were G1P[8] (43%), G12P[8] (15%) and G9P[8] (9%); 11% of children had mixed infection.G3P[8], which has not been reported in Bangladesh since 2001, was documented for the first time in our surveillance system. CONCLUSIONS: The high burden of rotavirus-associated hospitalizations highlights the potential value of rotavirus vaccination in Bangladesh. Continued surveillance is important for monitoring the impact of vaccination as well as monitoring evolving genotypes. PMID- 29793895 TI - Barriers and facilitators to HPV vaccination among rural Alabama adolescents and their caregivers. AB - INTRODUCTION: Half of all new human papillomavirus (HPV) infections occur in adolescents and young adults, and this population has poor HPV vaccination rates. Rural areas of the U.S. have high rates of HPV-related diseases and low vaccination rates as well. The purpose of this study was to determine the perceived barriers and facilitators to HPV vaccination among adolescents and their caregivers in rural south Alabama. METHODS: Vaccinated and non-vaccinated adolescents ages 11-18 years old and primary caregivers were recruited from three rural counties in south Alabama. Participants completed individual interviews to discuss perceived barriers to vaccination and factors influencing their decision to vaccinate. Discussion groups were held to determine potential solutions to barriers elucidated from the interviews. Interview and discussion group transcripts were analyzed, and themes were identified. RESULTS: Approximately 62.5% of adolescents had not initiated the HPV vaccine series. Of those adolescents who started the vaccine series (n = 9, 37.5%), about half completed it (n = 5). Few participants in this study reported speaking with their health care provider (HCP) about the vaccine in the past year. Lack of information about the vaccine, its side effects, and no HCP recommendation were common barriers cited by non-vaccinators. Facilitators to vaccination included cancer prevention, discussion with HCP, and peer testimonials. Potential solutions to barriers were also discussed. CONCLUSIONS: Proposed strategies to increase HPV vaccination were similar between vaccinated and non-vaccinated groups. Education about HPV and the HPV vaccine is needed throughout these rural south Alabama communities to ensure informed decisions are made about vaccination and to increase vaccination rates. PMID- 29793896 TI - What are the defining characteristics of the most cited publications in orthognathic surgery? AB - The purpose of this study was to identify the characteristics associated with highly cited papers in orthognathic surgery. This was a cohort study of articles published in the English-language literature from 1900 to 2017. Citation databases were searched for papers related to orthognathic surgery and the most frequently cited papers were identified. For each paper, the following variables were collected: region of origin, time-period of publication, corresponding author specialty, journal of publication, topic area, study design, and number of citations. The outcome variable was the citation index (citations per year). North American investigators published 70% of the 100 most-cited articles in orthognathic surgery. The majority of papers were from oral and maxillofacial surgeons. Frequent content areas were diagnosis, virtual planning, fixation/stability, and complications. The majority (54%) of studies were cohort or case report/series. The mean number of citations was 235.0+/-126.5; the mean citation index was 9.9+/-6.1 citations per year. Time-period, content area, and study design were associated with the citation index (all P<0.001). Time-period, content area, and study design predicted the citation index (all P<=0.009). Among frequently cited papers in orthognathic surgery, oral and maxillofacial surgeons had the highest volume of contributions. Diagnosis, treatment planning, and complications were the most common topics studied. PMID- 29793897 TI - Conservative management of severe coronary artery hematoma and dissection following stent implantation. AB - Severe dissection and hematoma following stent implantation can cause acute vessel closure, which requires an immediate bailout procedure. However, bailout from such a situation may not be easy, especially when the hematoma extends to the distal segment of a coronary artery. We present a case of 73-year-old woman with effort angina who underwent PCI to the right coronary artery (RCA). Following stent implantation, there was a massive hematoma from the distal edge of the stent. We tried to create re-entry at the distal part of the hematoma, but were not successful. We managed her conservatively without additional stent placement or creating re-entry. Follow-up coronary angiography on day 68 showed excellent coronary flow. Intravascular ultrasound demonstrated complete healing of the hematoma. A hematoma caused by edge dissection is a challenging complication. Additional stent implantation to cover the entire length of the hematoma and/or cutting balloon dilatation to create re-entry are options; however, these procedures may worsen the situation. Our case clearly showed healing of dissection and hematoma without creating re-entry or additional stent implantation. Conservative management should be considered an option for severe edge dissection and hematoma following stent implantation. PMID- 29793898 TI - Tryton dedicated bifurcation stent in treatment of unprotected distal left main bifurcation disease. AB - Percutaneous coronary interventions involving coronary bifurcation lesions are more complex and associated with adverse outcomes (both angiographic and clinical) compared to non-bifurcation lesions. Tryton, a dedicated bifurcation stent, has been introduced with the aim to simplify treatment of bifurcation lesions. Tryton stent in combination with conventional drug eluting stent is safe and associated with reduced stenosis and bail-out stenting of side branch compared to provisional stenting involving a large side. However, little is known regarding safety and efficacy of Tryton stent in left main (LM) bifurcation lesion. We describe two cases of unprotected LM bifurcation stenting using Tryton stent in combination with drug eluting stent. PMID- 29793899 TI - Attention and Cognitive Bias Modification Apps: Review of the Literature and of Commercially Available Apps. AB - BACKGROUND: Automatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically. OBJECTIVE: The objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically. METHODS: To identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were "attention bias" OR "cognitive bias" AND "smartphone" OR "smartphone application" OR "smartphone app" OR "mobile phones" OR "mobile application" OR mobile app" OR "personal digital assistant." To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were "attention bias" and "cognitive bias." We also conducted a manual search on the apps with published evaluations. RESULTS: The effectiveness of bias modification was reported in 7 of 8 trials that we identified in the published literature. Only 1 of the 8 previously evaluated apps was commercially available. The 17 commercial apps we identified tended to use either an attention visual search or gamified task. Only 1 commercial app had been evaluated in the published literature. CONCLUSIONS: This is perhaps the first review to synthesize the evidence for published mHealth attention bias apps. Our review demonstrated that evidence for mHealth attention bias apps is inconclusive, and quite a few commercial apps have not been validated scientifically. PMID- 29793900 TI - The Importance of Visit Notes on Patient Portals for Engaging Less Educated or Nonwhite Patients: Survey Study. AB - BACKGROUND: OpenNotes, a national initiative to share clinicians' visit notes with patients, can improve patient engagement, but effects on vulnerable populations are not known very well. OBJECTIVE: Our aim is to examine the importance of visit notes to nonwhite and less educated patients. METHODS: Patients at an urban academic medical center with an active patient portal account and >=1 available ambulatory visit note over the prior year were surveyed during June 2016 until September 2016. The survey was designed with patients and families and assessed importance of reading notes (scale 0-10) for (1) understanding health conditions, (2) feeling informed about care, (3) understanding the provider's thought process, (4) remembering the plan of care, and (5) making decisions about care. We compared the proportion of patients reporting 9-10 (extremely important) for each item stratified by education level, race/ethnicity, and self-reported health. Principal component analysis and correlation measures supported a summary score for the 5 items (Cronbach alpha=.93). We examined factors associated with rating notes as extremely important to engage in care using logistic regression. RESULTS: Of 24,722 patients, 6913 (27.96%) completed the survey. The majority (6736/6913, 97.44%) read at least one note. Among note readers, 74.0% (727/982) of patients with <=high school education, 70.7% (130/184) of black patients, and 69.9% (153/219) of Hispanic/Latino patients reported that notes are extremely important to feel informed about their care. The majority of less educated and nonwhite patients reported notes as extremely important to remember the care plan (62.4%, 613/982 <=high school education; 62.0%, 114/184 black patients; and 61.6%, 135/219 Hispanic/Latino patients) and to make care decisions (62.3%, 612/982; 59.8%, 110/184; and 58.5%, 128/219, respectively, and P<.003 for all comparisons to more educated and white patients, respectively). Among patients with the poorest self reported health, 65.9% (499/757) found notes extremely important to be informed and to understand the provider. On multivariable modeling, less educated patients were nearly three times as likely to report notes were extremely important to engage in care compared with the most educated patients (odds ratio [OR] 2.9, 95% CI 2.4-3.3). Nonwhite patients were twice as likely to report the same compared with white patients (OR 2.0, 95% CI 1.5-2.7 [black] and OR 2.2, 95% CI 1.6-2.9 [Hispanic/Latino and Asian], P<.001 for each comparison). Healthier patients, women, older patients, and those who read more notes were more likely to find notes extremely important to engage in care. CONCLUSIONS: Less educated and nonwhite patients using the portal each assigned higher importance to reading notes for several health behaviors than highly educated and white patients, and may find transparent notes especially valuable for understanding their health and engaging in their care. Facilitating access to notes may improve engagement in health care for some vulnerable populations who have historically been more challenging to reach. PMID- 29793901 TI - A Mobile App for Identifying Individuals With Undiagnosed Diabetes and Prediabetes and for Promoting Behavior Change: 2-Year Prospective Study. AB - BACKGROUND: To decrease the burden of diabetes in society, early screening of undiagnosed diabetes and prediabetes is needed. Integrating a diabetes risk score into a mobile app would provide a useful platform to enable people to self-assess their risk of diabetes with ease. OBJECTIVE: The objectives of this study were to (1) assess the profile of Diabetes Risk Score mobile app users, (2) determine the optimal cutoff value of the Finnish Diabetes Risk Score to identify undiagnosed diabetes and prediabetes in the Chinese population, (3) estimate users' chance of developing diabetes within 2 years of using the app, and (4) investigate high risk app users' lifestyle behavior changes after ascertaining their risk level from the app. METHODS: We conducted this 2-phase study among adults via mobile app and online survey from August 2014 to December 2016. Phase 1 adopted a cross sectional design, with a descriptive analysis of the app users' profile. We used a Cohen kappa score to show the agreement between the risk level (as shown in the app) and glycated hemoglobin test results. We used sensitivity, specificity, and area under the curve to determine the optimal cutoff value of the diabetes risk score in this population. Phase 2 was a prospective cohort study. We used a logistic regression model to estimate the chance of developing diabetes after using the app. Paired t tests compared high-risk app users' lifestyle changes. RESULTS: A total of 13,289 people used the app in phase 1a. After data cleaning, we considered 4549 of these as valid data. Most users were male, and 1811 (39.81%) had tertiary education or above. Among them, 188 (10.4%) users agreed to attend the health assessment in phase 1b. We recommend the optimal value of the diabetes risk score for identifying persons with undiagnosed diabetes and prediabetes to be 9, with an area under the receiver operating characteristic curve of 0.67 (95% CI 0.60-0.74), sensitivity of 0.70 (95% CI 0.58-0.80), and specificity of 0.57 (95% CI 0.47-0.66). At the 2-year follow-up, people in the high-risk group had a higher chance of developing diabetes (odds ratio 4.59, P=.048) than the low-risk group. The high-risk app users improved their daily intake of vegetables (baseline: mean 0.76, SD 0.43; follow-up: mean 0.93, SD 0.26; t81=-3.77, P<.001) and daily exercise (baseline: mean 0.40, SD 0.49; follow up: mean 0.54, SD 0.50; t81=-2.08, P=.04). CONCLUSIONS: The Diabetes Risk Score app has been shown to be a feasible and reliable tool to identify persons with undiagnosed diabetes and prediabetes and to predict diabetes incidence in 2 years. The app can also encourage high-risk people to modify dietary habits and reduce sedentary lifestyle. PMID- 29793902 TI - The Effects of Implicit and Explicit Motor Learning in Gait Rehabilitation of People After Stroke: Protocol for a Randomized Controlled Trial. AB - BACKGROUND: A significant part of neurological rehabilitation focuses on facilitating the learning of motor skills. Training can adopt either (more) explicit or (more) implicit forms of motor learning. Gait is one of the most practiced motor skills within rehabilitation in people after stroke because it is an important criterion for discharge and requirement for functioning at home. OBJECTIVE: The aim of this study was to describe the design of a randomized controlled study assessing the effects of implicit motor learning compared with the explicit motor learning in gait rehabilitation of people suffering from stroke. METHODS: The study adopts a randomized, controlled, single-blinded study design. People after stroke will be eligible for participation when they are in the chronic stage of recovery (>6 months after stroke), would like to improve walking performance, have a slow walking speed (<1 m/s), can communicate in Dutch, and complete a 3-stage command. People will be excluded if they cannot walk a minimum of 10 m or have other additional impairments that (severely) influence gait. Participants will receive 9 gait-training sessions over a 3-week period and will be randomly allocated to an implicit or explicit group. Therapists are aware of the intervention they provide, and the assessors are blind to the intervention participants receive. Outcome will be assessed at baseline (T0), directly after the intervention (T1), and after 1 month (T2). The primary outcome parameter is walking velocity. Walking performance will be assessed with the 10-meter walking test, Dynamic Gait Index, and while performing a secondary task (dual task). Self-reported measures are the Movement Specific Reinvestment Scale, verbal protocol, Stroke and Aphasia Quality of Life Scale, and the Global Perceived Effect scale. A process evaluation will take place to identify how the therapy was perceived and identify factors that may have influenced the effectiveness of the intervention. Repeated measures analyses will be conducted to determine significant and clinical relevant differences between groups and over time. RESULTS: Data collection is currently ongoing and results are expected in 2019. CONCLUSIONS: The relevance of the study as well as the advantages and disadvantages of several aspects of the chosen design are discussed, for example, the personalized approach and choice of measurements. TRIAL REGISTRATION: Netherlands Trial Register NTR6272; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6272 (Archived by WebCite http://www.webcitation.org/6ytA937m5). REGISTERED REPORT IDENTIFIER: RR1 10.2196/9595. PMID- 29793903 TI - Errata. PMID- 29793904 TI - Personal Exposure Prescription Method Reduces Dose in Radiography. AB - PURPOSE: To evaluate the effectiveness of an automatic, personalized exposure prescription method designed to reduce radiation dose during radiography examinations. METHODS: Using standard imaging parameters of average-sized patients, the authors measured individual body-part thicknesses or imaging regions of 116 patients (69 men, 47 women) and calculated each patient's exposure amount according to the thickness of the part or region. The data were used to develop each patient's personalized exposure prescription. Using the personalized exposure prescriptions, authors acquired chest images of the patients on a Carestream DRX-Revolution mobile digital radiography system. RESULTS: All images acquired using the personalized exposure prescription method were satisfactory for diagnosis; exposure indexes were above 1300, a figure deemed acceptable for diagnosis by the manufacturer. The personalized exposure method reduced the amount of radiation each patient received. DISCUSSION: Variation of tube voltage alone can control patients' exposure levels; however, using the personalized exposure prescription method eliminates the need to use automatic exposure controls. CONCLUSION: The personalized exposure prescription method is an effective tool for reducing radiation to patients during radiography as well as for eliminating dose creep. PMID- 29793906 TI - Shielding in Medical Imaging and Radiation Therapy. AB - The medical use of ionizing radiation accounts for almost half of the radiation exposure accumulated by people living in the United States each year. Although risks are associated with using radiation, materials and techniques are available to protect patients and medical personnel from excess radiation. This article reviews the nature of radiation, its effects on matter, and how shielding can help keep exposure levels as low as reasonably achievable. PMID- 29793905 TI - The Need for Cultural Competency in Health Care. AB - PURPOSE: To highlight the importance of cultural competency education in health care and in the medical imaging industry. METHODS: A comprehensive search of the Education Resource Information Center and MEDLINE databases was conducted to acquire full-text and peer-reviewed articles relating to cultural competency training in health care. RESULTS: A total of 1008 academic journal articles and 3 books were identified for this literature review. Search criteria was narrowed to peer-reviewed articles published between 2000 and 2016, resulting in 24 articles. A majority of the research studies addressed cultural competency education in allied health professions, as well as psychology and athletic training. Recent research studies pertaining to the cultural competence of imaging professionals were not found. DISCUSSION: Research shows that the behaviors of health care providers can contribute to health disparities. National standards have been established to promote patient-centered care that reduces or eliminates health disparities in the U.S. POPULATION: Lectures and training sessions help professionals maintain these standards, but they might not be adequate. Health care workers need to interact and work with diverse patient populations to increase their empathy and become culturally competent. CONCLUSION: A patient centered care approach that responds to patients' unique needs and reduces health disparities among diverse patient populations can be achieved by training culturally competent health care professionals. More research is needed to determine the nature of cultural competency education taught in radiography programs. PMID- 29793907 TI - Epilepsy and Magnetic Resonance Imaging. AB - Epilepsy is the most common neurological disease worldwide and a frequent cause of neurological morbidity. However, with advanced imaging techniques, accurate determination of epilepsy etiology is possible and can help optimize effective management of the disease. Magnetic resonance imaging plays an integral role in epilepsy diagnosis and treatment, including first-onset seizure workup, chronic epilepsy assessment, presurgical evaluation, magnetic resonance-guided laser induced thermal therapy, and postoperative monitoring. PMID- 29793908 TI - Conventional Film-Screen Principles of Exposure Selection in the Digital Age. PMID- 29793909 TI - Application of the BLADE Sequence in Upper Abdominal MR Imaging. PMID- 29793910 TI - Sexual Harassment in Medical Imaging. PMID- 29793912 TI - Maximum Spatial Gradient and Implant Safety in MR Imaging. PMID- 29793911 TI - Using MR to View PTSD's Effect on the Amygdala and Hippocampus. PMID- 29793914 TI - Embracing a Holistic Approach to Patient Care. PMID- 29793915 TI - Contrast-Enhanced Digital Mammography. PMID- 29793913 TI - DXA Scanning of the Lumbar Spine and Proximal Femur. PMID- 29793916 TI - Teaching Stomach Imaging to Radiography Students. PMID- 29793918 TI - What's Inside? PMID- 29793917 TI - Background Checks and Drug Screenings for Radiologic Science Students. PMID- 29793919 TI - Acute Kidney Injury and Iodinated Contrast Media. AB - Iodinated contrast agents used in computed tomography (CT) examinations have the potential to cause adverse reactions in patients. The possibility of acute kidney injury should be of concern to radiologic technologists performing CT examinations. Although prevention is paramount, identifying and treating contrast induced nephropathy, for example, as well as following appropriate guidelines regarding the handling and usage of contrast material, are crucial. This article discusses recent research in these areas. PMID- 29793920 TI - Adverse Effects and Imaging Appearances of Breast Implants. AB - Implants commonly are used to augment or reconstruct breasts but are associated with many adverse effects, both in the short term and years after implantation. This article discusses different types of breast implants and some of the common adverse effects associated with them including contracture, rupture, leakage, and infection. The clinical and imaging appearances of these adverse effects are presented. In addition, the article describes findings and recommendations regarding rare breast implant-associated adverse effects such as anaplastic large cell lymphoma and breast fibromatosis. PMID- 29793923 TI - Child obesity: government considers new direct interventions. PMID- 29793921 TI - Strategies to Enhance Data Collection and Analysis in Qualitative Research. PMID- 29793924 TI - GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever. AB - Pyroptosis is an inflammasome-induced lytic cell death mode, the physiological role of which in chronic inflammatory diseases is unknown. Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide, affecting an estimated 150,000 patients. The disease is caused by missense mutations in Mefv that activate the Pyrin inflammasome, but the pathophysiologic mechanisms driving autoinflammation in FMF are incompletely understood. Here, we show that Clostridium difficile infection of FMF knock-in macrophages that express a chimeric FMF-associated MefvV726A Pyrin elicited pyroptosis and gasdermin D (GSDMD)-mediated interleukin (IL)-1beta secretion. Importantly, in vivo GSDMD deletion abolished spontaneous autoinflammatory disease. GSDMD deficient FMF knock-in mice were fully protected from the runted growth, anemia, systemic inflammatory cytokine production, neutrophilia, and tissue damage that characterize this autoinflammatory disease model. Overall, this work identifies pyroptosis as a critical mechanism of IL-1beta-dependent autoinflammation in FMF and highlights GSDMD inhibition as a potential antiinflammatory strategy in inflammasome-driven diseases. PMID- 29793926 TI - Choriocapillaris and retinal vascular plexus density of diabetic eyes using split spectrum amplitude decorrelation spectral-domain optical coherence tomography angiography. AB - BACKGROUND/AIMS: Split-spectrum amplitude decorrelation angiography for spectral domain optical coherence tomography has enabled detailed, non-invasive assessment of vascular flow. This study evaluates choriocapillaris and retinal capillary perfusion density (CPD) in diabetic eyes using optical coherence tomography angiography (OCTA). METHODS: Records of 136 eyes that underwent OCTA imaging at a single institution were reviewed. Eyes were grouped as non-diabetic controls (37 eyes), patients with diabetes mellitus (DM) without diabetic retinopathy (DM without DR, 31 eyes), non-proliferative diabetic retinopathy (NPDR, 41 eyes) and proliferative diabetic retinopathy (PDR, 27 eyes). Quantitative CPD analyses were performed on OCTA images for assessing perfusion density of the choriocapillaris and retinal plexus for all patients and compared between groups. RESULTS: Eyes with NPDR and PDR showed significantly decreased choriocapillaris CPD compared with controls, while DM eyes without DR did not show significant change. Choriocapillaris whole-image CPD was decreased by 8.3% in eyes with NPDR (p<0.01) and decreased by 7.1% in eyes with PDR (p<0.01). Choriocapillaris parafoveal CPD was decreased by 8.9% in eyes with NPDR (p<0.01) and decreased by 8.2% in eyes with PDR (p<0.01). Compared with controls, only eyes with PDR showed significantly decreased retinal CPD, as well as significantly increased foveal avascular zone (FAZ) area. In those patients, retinal whole-image CPD was decreased by 9.7% (p<0.01), retinal foveal CPD was decreased by 20.5% (p<0.01) and retinal parafoveal CPD was decreased by 11.4% (p<0.01). FAZ area was increased by 50.9% (p<0.01). CONCLUSIONS: Choriocapillaris and retinal CPD are reduced in diabetic retinopathy, while FAZ area is increased in eyes with PDR. Vascular changes captured by new imaging modalities can further characterise diabetic choroidopathy. PMID- 29793925 TI - Rapid assessment of avoidable blindness in Papua New Guinea: a nationwide survey. AB - OBJECTIVE: To estimate the prevalence and main causes of blindness and vision impairment in people aged 50 years and older in Papua New Guinea (PNG). DESIGN: National cross-sectional population-based survey in National Capital District (NCD), Highlands, Coastal and Islands regions. METHODS: Adults aged 50 years and above were recruited from 100 randomly selected clusters. Each participant underwent monocular presenting and pinhole visual acuity (VA) assessment and lens examination. Those with pinhole VA<6/12 in either eye had a dilated fundus examination to determine the primary cause of reduced vision. Those with obvious lens opacity were interviewed on barriers to cataract surgery. RESULTS: A total of 4818 adults were examined. The age-adjusted and sex-adjusted prevalence of blindness (VA <3/60), severe vision impairment (SVI, VA <6/60 but >=3/60), moderate vision impairment (MVI, VA <6/18 but >=6/60) and early vision impairment (EVI, VA <6/12 but >=6/18) was 5.6% (95% CI 4.9% to 6.3%), 2.9% (95% CI 2.5% to 3.4%), 10.9% (95% CI 9.9% to 11.9%) and 7.3% (95% CI 6.6% to 8.0%), respectively. The main cause of blindness, SVI and MVI was cataract, while uncorrected refractive error was the main cause of EVI. A significantly higher prevalence of blindness, SVI and MVI occurred in the Highlands compared with NCD. Across all regions, women had lower cataract surgical coverage and spectacle coverage than men. CONCLUSIONS: PNG has one of the highest reported prevalence of blindness globally. Cataract and uncorrected refractive error are the main causes, suggesting a need for increased accessible services with improved resources and advocacy for enhancing eye health literacy. PMID- 29793928 TI - Optic nerve head cupping in glaucomatous and non-glaucomatous optic neuropathy. AB - BACKGROUND: Enlargement of optic disc cupping is seen both in glaucoma and in neurological disorders. We used enhanced depth imaging with spectral-domain optical coherence tomography to differentiate glaucoma from non-glaucomatous optic neuropathy. METHODS: The optic discs were scanned in this prospective comparative study, and the lamina cribrosa (LC) thickness and anterior laminar depth (ALD) in the central, superior and inferior optic nerve head, and peripapillary choroidal thicknesses, were measured. RESULTS: There were 31 eyes of 31 patients with severe glaucoma and 33 eyes of 19 patients with non glaucomatous cupping. Eyes of 29 healthy controls were also enrolled. There was no significant difference in the cup-to-disc ratio and in the average peripapillary nerve fibre layer thickness between the glaucoma and non glaucomatous cupping groups (p>0.99). The average peripapillary choroidal thickness was thinner in glaucoma eyes than in the control eyes after adjusting for age and axial length. Glaucomatous and non-glaucomatous eyes had greater ALD and thinner LC than the control eyes (p<0.001 for both). ALDs of glaucoma eyes were deeper than non-glaucomatous eyes (p=0.01 for central ALD) when age, axial length and peripapillary choroidal thickness were included in the linear mixed model. Prelaminar thickness and LC thickness of glaucoma eyes were not different from non-glaucomatous eyes after adjusting. CONCLUSION: Deeper ALD was observed in glaucoma than non-glaucomatous cupping after adjusting for choroidal thickness. PMID- 29793927 TI - Seasonal variation of refractive error change among young schoolchildren in a population-based cohort study in Taipei. AB - PURPOSE: To investigate the relationship between seasonal variation of daylight length and spherical equivalent (SE) progression among the schoolchildren participating in the Myopia Investigation Study in Taipei. METHODS: We used the first-year data from grade 2 schoolchildren who completed all the baseline and two follow-up examinations (n=6790). There were two 6-month intervals between visits over winter and summer, respectively. For each interval, we calculated average daily daylight length using data from Taiwan's Central Weather Bureau and measured 6-month SE progression rate based on right eye cycloplegic autorefraction data. The midpoint month was defined as the month midway between two consecutive visits. RESULTS: By the midpoint month, average daily daylight length was the shortest in December (671+/-7 min/day) and the longest (785+/-7 min/day) in June, and SE progression rate was the fastest (-0.23+/-0.48 D) in December and the slowest (-0.17+/-0.51 D) in June. Significant variation of SE progression rate with season can be observed only among the schoolchildren (n=1905) whose midpoint months for the winter and summer intervals were December and June (winter rate, -0.25+/-0.47 D; summer rate, -0.17+/-0.49 D; p<0.001). Of those, the summer progression rate was approximately 80%, 65% and 61.5% of that measured in winter for myopic (p=0.252), emmetropic (p=0.012) and hyperopic (p=0.012) schoolchildren, respectively. CONCLUSION: Our data demonstrate a seasonal variation of minus shift in refractive error among Taipei schoolchildren who had significant daytime fluctuation during the 1-year follow-up. Of those, non-myopic children had significant and more pronounced variation of SE progression than myopic children. PMID- 29793929 TI - Financial disincentives? A three-armed randomised controlled trial of the effect of financial Incentives in Diabetic Eye Assessment by Screening (IDEAS) trial. AB - OBJECTIVE: Conflicting evidence exists regarding the impact of financial incentives on encouraging attendance at medical screening appointments. The primary aim was to determine whether financial incentives increase attendance at diabetic eye screening in persistent non-attenders. METHODS AND ANALYSIS: A three armed randomised controlled trial was conducted in London in 2015. 1051 participants aged over 16 years, who had not attended eye screening appointments for 2 years or more, were randomised (1.4:1:1 randomisation ratio) to receive the usual invitation letter (control), an offer of L10 cash for attending screening (fixed incentive) or a 1 in 100 chance of winning L1000 (lottery incentive) if they attend. The primary outcome was the proportion of invitees attending screening, and a comparative analysis was performed to assess group differences. Pairwise comparisons of attendance rates were performed, using a conservative Bonferroni correction for independent comparisons. RESULTS: 34/435 (7.8%) of control, 17/312 (5.5%) of fixed incentive and 10/304 (3.3%) of lottery incentive groups attended. Participants who received any incentive were significantly less likely to attend their appointment compared with controls (risk ratio (RR)=0.56; 95% CI 0.34 to 0.92). Those in the probabilistic incentive group (RR=0.42; 95% CI 0.18 to 0.98), but not the fixed incentive group (RR=1.66; 95% CI 0.65 to 4.21), were significantly less likely to attend than those in the control group. CONCLUSION: Financial incentives, particularly lottery-based incentives, attract fewer patients to diabetic eye screening than standard invites in this population. Financial incentives should not be used to promote screening unless tested in context, as they may negatively affect attendance rates. PMID- 29793930 TI - Possible connection of short posterior ciliary arteries to choroidal neovascularisations in eyes with pathologic myopia. AB - PURPOSE: To determine the connection between myopic choroidal neovascularisations (CNVs) and intrascleral vessels examined by swept-source optical coherence tomography (OCT). METHODS: The data of 124 eyes of 112 consecutive patients with myopic CNVs were retrospectively analysed. A myopic CNV was defined as a CNV occurring in eyes with pathologic myopia based on the META-PM study classification. The images obtained by swept-source OCT were analysed to determine the relationship between perforating scleral vessels and CNVs. The continuity of the scleral vessels and the CNV was also analysed. The OCT angiographic (OCTA) characteristics of the myopic CNVs at the active, scar and atrophic phases were also analysed. RESULTS: OCTA images showed that CNVs had blood flow in the active, scar and atrophic phases. Scleral perforating vessels were detected just below or around the CNV in 93 eyes (75%). In 10 of the 93 eyes, the scleral vessels and CNV appeared to be continuous through a defect of Bruch's membrane in the OCT images. Indocyanine green angiography showed that these perforating vessels were intrascleral arteries originating from the short posterior ciliary arteries (SPCAs). CONCLUSIONS: Swept-source OCT showed that some of the myopic CNVs were continuous with scleral vessels mainly the SPCA. Further studies to confirm angiographical continuity between these two components are necessary. PMID- 29793931 TI - Asymmetric Golgi Repositioning: A Prerequisite for Appropriate Dendrite Formation in Adult-Born Neurons. PMID- 29793932 TI - Primary care is a neglected resource for clinical research. PMID- 29793934 TI - Trends in Noncardiovascular Comorbidities Among Patients Hospitalized for Heart Failure: Insights From the Get With The Guidelines-Heart Failure Registry. AB - BACKGROUND: The increase in medical complexity among patients hospitalized with heart failure (HF) may be reflected by an increase in concomitant noncardiovascular comorbidities. Among patients hospitalized with HF, the temporal trends in the prevalence of noncardiovascular comorbidities have not been well described. METHODS AND RESULTS: We used data from 207 984 patients in the Get With The Guidelines-Heart Failure registry (from 2005 to 2014) to evaluate the prevalence and trends of noncardiovascular comorbidities (chronic obstructive pulmonary disorder/asthma, anemia, diabetes mellitus, obesity [body mass index >=30 kg/m2], and renal impairment) among patients hospitalized with HF. Medicare beneficiaries aged >=65 years were used to assess 30-day mortality. The prevalence of 0, 1, 2, and >=3 noncardiovascular comorbidities was 18%, 30%, 27%, 25%, respectively. From 2005 to 2014, there was a decline in patients with 0 noncardiovascular comorbidities (22%-16%; P<0.0001) and an increase in patients with >=3 noncardiovascular comorbidities (18%-29%; P<0.0001). Among Medicare beneficiaries, there was an increased 30-day adjusted mortality risk among patients with 1 noncardiovascular comorbidity (hazard ratio, 1.16; 95% confidence interval, 1.09-1.24; P<0.0001), 2 noncardiovascular comorbidities (hazard ratio, 1.34; 95% confidence interval, 1.25-1.44; P<0.0001), and >=3 noncardiovascular comorbidities (hazard ratio, 1.63; 95% confidence interval, 1.51-1.75; P<0.0001). Similar trends were seen for in-hospital mortality. CONCLUSIONS: Patients admitted in hospital for HF have an increasing number of noncardiovascular comorbidities over time, which are associated with worse outcomes. Strategies addressing the growing burden of noncardiovascular comorbidities may represent an avenue to improve outcomes and should be included in the delivery of in-hospital HF care. PMID- 29793933 TI - Tetrodotoxin-sensitive Navs contribute to early and delayed afterdepolarizations in long QT arrhythmia models. AB - Recent evidence suggests that neuronal Na+ channels (nNavs) contribute to catecholamine-promoted delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardia (CPVT). The newly identified overlap between CPVT and long QT (LQT) phenotypes has stoked interest in the cross-talk between aberrant Na+ and Ca2+ handling and its contribution to early afterdepolarizations (EADs) and DADs. Here, we used Ca2+ imaging and electrophysiology to investigate the role of Na+ and Ca2+ handling in DADs and EADs in wild-type and cardiac calsequestrin (CASQ2)-null mice. In experiments, repolarization was impaired using 4-aminopyridine (4AP), whereas the L-type Ca2+ and late Na+ currents were augmented using Bay K 8644 (BayK) and anemone toxin II (ATX-II), respectively. The combination of 4AP and isoproterenol prolonged action potential duration (APD) and promoted aberrant Ca2+ release, EADs, and DADs in wild-type cardiomyocytes. Similarly, BayK in the absence of isoproterenol induced the same effects in CASQ2-null cardiomyocytes. In vivo, it prolonged the QT interval and, upon catecholamine challenge, precipitated wide QRS polymorphic ventricular tachycardia that resembled human torsades de pointes. Treatment with ATX-II produced similar effects at both the cellular level and in vivo. Importantly, nNav inhibition with riluzole or 4,9-anhydro-tetrodotoxin reduced the incidence of ATX-II-, BayK-, or 4AP-induced EADs, DADs, aberrant Ca2+ release, and VT despite only modestly mitigating APD prolongation. These data reveal the contribution of nNaVs to triggered arrhythmias in murine models of LQT and CPVT LQT overlap phenotypes. We also demonstrate the antiarrhythmic impact of nNaV inhibition, independent of action potential and QT interval duration, and provide a basis for a mechanistically driven antiarrhythmic strategy. PMID- 29793935 TI - The scale of life and its lessons for humanity. PMID- 29793937 TI - Revisiting sources of left-handedness in multiple-birth individuals. PMID- 29793938 TI - Metastable quasicrystal-induced nucleation in a bulk glass-forming liquid. AB - This study presents a unique Mg-based alloy composition in the Mg-Zn-Yb system which exhibits bulk metallic glass, metastable icosahedral quasicrystals (iQCs), and crystalline approximant phases in the as-cast condition. Microscopy revealed a smooth gradual transition from glass to QC. We also report the complete melting of a metastable eutectic phase mixture (including a QC phase), generated via suppression of the metastable-to-stable phase transition at high heating rates using fast differential scanning calorimetry (FDSC). The melting temperature and enthalpy of fusion of this phase mixture could be measured directly, which unambiguously proves its metastability in any temperature range. The kinetic pathway from liquid state to stable solid state (an approximant phase) minimizes the free-energy barrier for nucleation through an intermediate state (metastable QC phase) because of its low solid-liquid interfacial energy. At high undercooling of the liquid, where diffusion is limited, another approximant phase with near-liquid composition forms just above the glass-transition temperature. These experimental results shed light on the competition between metastable and stable crystals, and on glass formation via system frustration associated with the presence of several free-energy minima. PMID- 29793936 TI - Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell platelet-monocyte interaction. AB - Monocyte extravasation into the vessel wall is a key step in atherogenesis. It is still elusive how monocytes transmigrate through the endothelial cell (EC) monolayer at atherosclerosis predilection sites. Platelets tethered to ultra large von Willebrand factor (ULVWF) multimers deposited on the luminal EC surface following CD40 ligand (CD154) stimulation may facilitate monocyte diapedesis. Human ECs grown in a parallel plate flow chamber for live-cell imaging or Transwell permeable supports for transmigration assay were exposed to fluid or orbital shear stress and CD154. Human isolated platelets and/or monocytes were superfused over or added on top of the EC monolayer. Plasma levels and activity of the ULVWF multimer-cleaving protease ADAMTS13 were compared between coronary artery disease (CAD) patients and controls and were verified by the bioassay. Two photon intravital microscopy was performed to monitor CD154-dependent leukocyte recruitment in the cremaster microcirculation of ADAMTS13-deficient versus wild type mice. CD154-induced ULVWF multimer-platelet string formation on the EC surface trapped monocytes and facilitated transmigration through the EC monolayer despite high shear stress. Two-photon intravital microscopy revealed CD154 induced ULVWF multimer-platelet string formation preferentially in venules, due to strong EC expression of CD40, causing prominent downstream leukocyte extravasation. Plasma ADAMTS13 abundance and activity were significantly reduced in CAD patients and strongly facilitated both ULVWF multimer-platelet string formation and monocyte trapping in vitro. Moderate ADAMTS13 deficiency in CAD patients augments CD154-mediated deposition of platelet-decorated ULVWF multimers on the luminal EC surface, reinforcing the trapping of circulating monocytes at atherosclerosis predilection sites and promoting their diapedesis. PMID- 29793939 TI - Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish. AB - Box jellyfish and vertebrates are separated by >500 million years of evolution yet have structurally analogous lens eyes that employ rhodopsin photopigments for vision. All opsins possess a negatively charged residue-the counterion-to maintain visible-light sensitivity and facilitate photoisomerization of their retinaldehyde chromophore. In vertebrate rhodopsins, the molecular evolution of the counterion position-from a highly conserved distal location in the second extracellular loop (E181) to a proximal location in the third transmembrane helix (E113)-is established as a key driver of higher fidelity photoreception. Here, we use computational biology and heterologous action spectroscopy to determine whether the appearance of the advanced visual apparatus in box jellyfish was also accompanied by changes in the opsin tertiary structure. We found that the counterion in an opsin from the lens eye of the box jellyfish Carybdea rastonii (JellyOp) has also moved to a unique proximal location within the transmembrane bundle-E94 in TM2. Furthermore, we reveal that this Schiff base/counterion system includes an additional positive charge-R186-that has coevolved with E94 to functionally separate E94 and E181 in the chromophore-binding pocket of JellyOp. By engineering this pocket-neutralizing R186 and E94, or swapping E94 with the vertebrate counterion E113-we can recreate versions of the invertebrate and vertebrate counterion systems, respectively, supporting a relatively similar overall architecture in this region of animal opsins. In summary, our data establish the third only counterion site in animal opsins and reveal convergent evolution of tertiary structure in opsins from distantly related species with advanced visual systems. PMID- 29793940 TI - Importance of dispersal in the assembly of the Neotropical biota. PMID- 29793942 TI - Problem gambling: five minutes with . . . Henrietta Bowden-Jones. PMID- 29793941 TI - Sampling the insects of the amber forest. PMID- 29793943 TI - Andrew Goddard: Brilliant dreamer. PMID- 29793944 TI - RCGP calls for national campaign to tackle loneliness. PMID- 29793945 TI - Is BMI the best measure of obesity? PMID- 29793947 TI - Comprehensive Profiling of DNA Repair Defects in Breast Cancer Identifies a Novel Class of Endocrine Therapy Resistance Drivers. AB - Purpose: This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease.Experimental Design: Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response in neoadjuvant aromatase inhibitor therapy trials (discovery dataset), with outcomes in METABRIC, TCGA, and Loi datasets (validation datasets), and in patient-derived xenografts. A causal relationship between candidate DDR genes and endocrine treatment response, and the underlying mechanism, was then tested in ER+ breast cancer cell lines.Results: Correlations between loss of expression of three genes: CETN2 (P < 0.001) and ERCC1 (P = 0.01) from the nucleotide excision repair (NER) and NEIL2 (P = 0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery dataset, and subsequently validated in independent patient cohorts. Complementary mutation analysis supported associations between mutations in NER and BER genes and reduced endocrine treatment response. A causal role for CETN2, NEIL2, and ERCC1 loss in intrinsic endocrine resistance was experimentally validated in ER+ breast cancer cell lines, and in ER+ patient-derived xenograft models. Loss of CETN2, NEIL2, or ERCC1 induced endocrine treatment resistance by dysregulating G1-S transition, and therefore, increased sensitivity to CDK4/6 inhibitors. A combined DDR signature score was developed that predicted poor outcome in multiple patient cohorts.Conclusions: This report identifies DDR defects as a new class of endocrine treatment resistance drivers and indicates new avenues for predicting efficacy of CDK4/6 inhibition in the adjuvant treatment setting. Clin Cancer Res; 24(19); 4887-99. (c)2018 AACR. PMID- 29793946 TI - Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer. AB - Purpose: This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer.Patients and Methods: Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1.Results: Median treatment duration was 4.6 (range: 0.9-40.5) months. All patients experienced >=1 AE, 30 (50.0%) had grade >=3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of 60 patients had evaluable tissue for central PIK3CA mutation testing [20 had mutations, 27 had no mutation detected (MND)]. In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA mutations [best confirmed response rate: 38.5% (5/13; 95% CI, 13.9-68.4); clinical benefit rate (CBR): 38.5% (5/13; 95% CI, 13.9-68.4)], PIK3CA-MND [best confirmed response rate: 14.3% (3/21; 95% CI, 3.0-36.3); CBR: 23.8% (5/21; 95% CI, 8.2-47.2)], and unknown PIK3CA mutation status [best confirmed response rate: 20.0% (2/10; 95% CI, 2.5-55.6); CBR: 30.0% (3/10; 95% CI, 6.7-65.2)].Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (vs. -MND) locally advanced or metastatic HER2-negative, HR positive breast cancer. No new safety signals were reported. A confirmatory phase III trial is ongoing. Clin Cancer Res; 24(18); 4380-7. (c)2018 AACR. PMID- 29793948 TI - Canine Distemper Virus Spread and Transmission to Naive Ferrets: Selective Pressure on SLAM-Dependent Entry. AB - Upon infection, morbilliviruses such as measles, rinderpest, and canine distemper virus (CDV) initially target immune cells via the signalling lymphocyte activation molecule (SLAM) before spreading to respiratory epithelia through the adherens junction protein nectin-4. However, the roles of these receptors in transmission from infected to naive hosts have not yet been formally tested. Towards experimentally addressing this question, we established a model of CDV contact transmission between ferrets. We show here that transmission of wild type CDV sometimes precedes the onset of clinical disease. In contrast, transmission was not observed in most animals infected with SLAM- or nectin-4-blind CDVs, even though all animals infected with the nectin-4-blind virus developed sustained viremia. There was an unexpected case of transmission of a nectin-4-blind virus, possibly due to biting. Another unprecedented event was transient viremia in an infection with a SLAM-blind virus. We identified three compensatory mutations within or near its SLAM-binding surface of the attachment protein. A recombinant CDV expressing the mutated attachment protein regained the ability to infect ferret lymphocytes in vitro, but its replication was not as efficient as wild type CDV. Ferrets infected with this virus developed transient viremia and fever, but there was no transmission to naive contacts. Our study supports the importance of epithelial cell infection, and of sequential CDV H protein interactions first with SLAM and then nectin-4 receptors for transmission to naive hosts. It also highlights the in vivo selection pressure on the H protein interactions with SLAM.IMPORTANCE Morbilliviruses such as measles, rinderpest, and canine distemper virus (CDV) are highly contagious. Despite extensive knowledge of how morbilliviruses interact with their receptors, little is known about how those interactions influence viral transmission to naive hosts. In a ferret model of CDV contact transmission, we show that sequential use of the signaling lymphocytic activation molecule (SLAM) and nectin-4 receptors is essential for transmission. In one animal infected with a SLAM-blind CDV, we documented mild viremia due to the acquisition of three compensatory mutations within or near its SLAM-binding surface. The interaction, however, was not sufficient to cause disease or sustain transmission to naive contacts. This work confirms the sequential roles of SLAM and nectin-4 in morbillivirus transmission, and highlights the selective pressure directed toward productive interactions with SLAM. PMID- 29793949 TI - Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load. AB - Despite decades of focused research, the field has yet to develop a prophylactic vaccine for HIV-1 infection. In the RV144 vaccine trial, nonneutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) subsets to the development of nonneutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24, and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterizations of cTfh cells were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed the differentiation of functional cTfh subsets toward increased Tfh1 (P = 0.02) and Tfh2 (P < 0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (which shares both Tfh1 and Tfh17 properties) (P = 0.01) and Tfh17 (P < 0.0001) subsets, compared to the subsets found in HIV-negative subjects. Interestingly, the frequencies of Tfh1 cells during acute infection (5.0 to 8.0 weeks postinfection) correlated negatively with the set point viral load (P = 0.03, Spearman rho [r] = -60) and were predictive of p24-specific plasma IgG titers at 1 year of infection (P = 0.003, r = 0.85). Taken together, our results suggest that the circulating Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long-lasting anti-HIV antibody responses.IMPORTANCE The HIV epidemic in southern Africa accounts for almost half of the global HIV burden, with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with a lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting nonneutralizing antibodies during HIV-1 infection. PMID- 29793950 TI - Similar Epitope Specificities of IgG and IgA Antibodies Elicited by Ad26 Vector Prime, Env Protein Boost Immunizations in Rhesus Monkeys. AB - Vaccine-elicited immunoglobulin G (IgG) has been shown to be important for protection against simian-human immunodeficiency virus (SHIV) infection in rhesus monkeys. However, it remains unclear whether vaccine-elicited IgA responses are beneficial or detrimental for protection. In this study, we evaluated the kinetics, magnitude, breadth, and linear epitope specificities of vaccine elicited IgG and IgA responses in serum and mucosal secretions following intramuscular immunization with adenovirus 26 (Ad26) prime, Env protein boost vaccination regimens. The systemic and mucosal antibody responses exhibited kinetics similar to those of the serum antibody responses but lower titers than the serum antibody responses. Moreover, the IgG and IgA responses were correlated, both in terms of the magnitude of the responses and in terms of the antibody specificities against linear human immunodeficiency virus type 1 (HIV-1) Env, Gag, and Pol epitopes. These data suggest that IgG and IgA responses are highly coordinated in both peripheral blood and mucosal compartments following Ad26/Env vaccination in rhesus monkeys.IMPORTANCE Vaccine-elicited IgG responses are important for protection against simian-human immunodeficiency virus (SHIV) infection in nonhuman primates. However, much less is known about the role and function of IgA, despite it being the predominant antibody in mucosal sites. There is debate as to whether HIV-1-specific IgA responses are beneficial or detrimental, since serum anti-Env IgA titers were shown to be inversely correlated with protection in the RV144 clinical trial. We thus assessed vaccine elicited IgG and IgA antibody responses in peripheral blood and mucosal secretions following vaccination with the Ad26/Env vaccine. PMID- 29793951 TI - Varicella-Zoster Virus ORF9p Binding to Cellular Adaptor Protein Complex 1 Is Important for Viral Infectivity. AB - ORF9p (homologous to herpes simplex virus 1 [HSV-1] VP22) is a varicella-zoster virus (VZV) tegument protein essential for viral replication. Even though its precise functions are far from being fully described, a role in the secondary envelopment of the virus has long been suggested. We performed a yeast two-hybrid screen to identify cellular proteins interacting with ORF9p that might be important for this function. We found 31 ORF9p interaction partners, among which was AP1M1, the MU subunit of the adaptor protein complex 1 (AP-1). AP-1 is a heterotetramer involved in intracellular vesicle-mediated transport and regulates the shuttling of cargo proteins between endosomes and the trans-Golgi network via clathrin-coated vesicles. We confirmed that AP-1 interacts with ORF9p in infected cells and mapped potential interaction motifs within ORF9p. We generated VZV mutants in which each of these motifs was individually impaired and identified leucine 231 in ORF9p to be critical for the interaction with AP-1. Disrupting ORF9p binding to AP-1 by mutating leucine 231 to alanine in ORF9p strongly impaired viral growth, most likely by preventing efficient secondary envelopment of the virus. Leucine 231 is part of a dileucine motif conserved among alphaherpesviruses, and we showed that VP22 of Marek's disease virus and HSV-2 also interacts with AP-1. This indicates that the function of this interaction in secondary envelopment might be conserved as well.IMPORTANCE Herpesviruses are responsible for infections that, especially in immunocompromised patients, can lead to severe complications, including neurological symptoms and strokes. The constant emergence of viral strains resistant to classical antivirals (mainly acyclovir and its derivatives) pleads for the identification of new targets for future antiviral treatments. Cellular adaptor protein (AP) complexes have been implicated in the correct addressing of herpesvirus glycoproteins in infected cells, and the discovery that a major constituent of the varicella-zoster virus tegument interacts with AP-1 reveals a previously unsuspected role of this tegument protein. Unraveling the complex mechanisms leading to virion production will certainly be an important step in the discovery of future therapeutic targets. PMID- 29793954 TI - Function of the Nonconserved N-Terminal Domain of Pseudorabies Virus pUL31 in Nuclear Egress. AB - Nuclear egress of herpesvirus capsids is mediated by the conserved nuclear egress complex (NEC), composed of the membrane-anchored pUL34 and its nucleoplasmic interaction partner, pUL31. The recently solved crystal structures of the NECs from different herpesviruses show a high structural similarity, with the pUL34 homologs building a platform recruiting pUL31 to the inner nuclear membrane. Both proteins possess a central globular fold, while the conserved N-terminal portion of pUL31 forms an extension reaching around the core of pUL34. However, the extreme N terminus of the pUL31 homologs, which is highly variable in length and amino acid composition, had to be removed for crystallization. Several pUL31 homologs contain a classical nuclear localization signal (NLS) within this part mediating efficient nuclear import. In addition, membrane-binding activity, blocking premature interaction with pUL34, nucleocapsid trafficking, and regulation of NEC assembly and disassembly via phosphorylation were assigned to the extreme pUL31 N terminus. To test the functional importance in the alphaherpesvirus pseudorabies virus (PrV) pUL31, N-terminal truncations and site specific mutations were generated, and the resulting proteins were tested for intracellular localization, interaction with pUL34, and functional complementation of PrV-DeltaUL31. Our data show that neither the bipartite NLS nor the predicted phosphorylation sites are essential for pUL31 function during nuclear egress. Moreover, nearly the complete variable N-terminal part was dispensable for function as long as a stretch of basic amino acids was retained. Phosphorylation of this domain controls efficient nucleocapsid release from the perinuclear space.IMPORTANCE Nuclear egress of herpesvirus capsids is a unique vesicle-mediated nucleocytoplasmic transport. Crystal structures of the heterodimeric NECs from different herpesviruses provided important details of this viral nuclear membrane deformation and scission machinery but excluded the highly variable N terminus of the pUL31 component. We present here a detailed mutagenesis study of this important portion of pUL31 and show that basic amino acid residues within this domain play an essential role for proper targeting, complex formation, and function during nuclear egress, while phosphorylation modulates efficient release from the perinuclear space. Thus, our data complement previous structure-function assignments of the nucleocapsid-interacting component of the NEC. PMID- 29793952 TI - Herpes Simplex Virus 1 Tegument Protein VP22 Abrogates cGAS/STING-Mediated Antiviral Innate Immunity. AB - Cytosolic DNA arising from intracellular pathogens is sensed by cyclic GMP-AMP synthase (cGAS) and triggers a powerful innate immune response. However, herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, has developed multiple mechanisms to attenuate host antiviral machinery and facilitate viral infection and replication. In the present study, we found that HSV-1 tegument protein VP22 acts as an inhibitor of cGAS/stimulator of interferon genes (cGAS/STING)-mediated production of interferon (IFN) and its downstream antiviral genes. Our results showed that ectopic expression of VP22 decreased cGAS/STING-mediated IFN-beta promoter activation and IFN-beta production. Infection with wild-type (WT) HSV-1, but not VP22-deficient virus (DeltaVP22), inhibited immunostimulatory DNA (ISD) induced activation of the IFN signaling pathway. Further study showed that VP22 interacted with cGAS and inhibited the enzymatic activity of cGAS. In addition, stable knockdown of cGAS facilitated the replication of DeltaVP22 virus but not the WT. In summary, our findings indicate that HSV-1 VP22 acts as an antagonist of IFN signaling to persistently evade host innate antiviral responses.IMPORTANCE cGAS is very important for host defense against viral infection, and many viruses have evolved ways to target cGAS and successfully evade the attack by the immune system of their susceptible host. This study demonstrated that HSV-1 tegument protein VP22 counteracts the cGAS/STING-mediated DNA-sensing antiviral innate immunity signaling pathway by inhibiting the enzymatic activity of cGAS. The findings in this study will expand our understanding of the interaction between HSV-1 replication and the host DNA-sensing signaling pathway. PMID- 29793953 TI - N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro. AB - Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles. However, NTCP reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles. Here, we investigated whether NTCP could explain the different behaviors of the two cell types. Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence. HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant. Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation. Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells. In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection. The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor. However, HepG2/NTCP cells remain poorly susceptible to patient serum derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV. We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence. NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture derived HBV or to confer susceptibility to serum-derived HBV. Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens. These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV. PMID- 29793955 TI - Nsp1alpha of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83. AB - Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection. One mechanism used by viruses to evade the immune system is to cripple the antigen-processing machinery in monocyte-derived dendritic cells (MoDCs). In this study, we show that MoDCs infected by PRRSV express lower levels of the major histocompatibility complex (MHC)-peptide complex proteins TAP1 and ERp57 and are impaired in their ability to stimulate T cell proliferation and increase their production of CD83. Neutralization of sCD83 removes the inhibitory effects of PRRSV on MoDCs. When MoDCs are incubated with exogenously added sCD83 protein, TAP1 and ERp57 expression decreases and T lymphocyte activation is impaired. PRRSV nonstructural protein 1alpha (Nsp1alpha) enhances CD83 promoter activity. Mutations in the ZF domain of Nsp1alpha abolish its ability to activate the CD83 promoter. We generated recombinant PRRSVs with mutations in Nsp1alpha and the corresponding repaired PRRSVs. Viruses with Nsp1alpha mutations did not decrease levels of TAP1 and ERp57, impair the ability of MoDCs to stimulate T cell proliferation, or increase levels of sCD83. We show that the ZF domain of Nsp1alpha stimulates the secretion of CD83, which in turn inhibits MoDC function. Our study provides new insights into the mechanisms of immune suppression by PRRSV.IMPORTANCE PRRSV has a severe impact on the swine industry throughout the world. Understanding the mechanisms by which PRRSV infection suppresses the immune system is essential for a robust and sustainable swine industry. Here, we demonstrated that PRRSV infection manipulates MoDCs by interfering with their ability to produce proteins in the MHC-peptide complex. The virus also impairs the ability of MoDCs to stimulate cell proliferation, due in large part to the enhanced release of soluble CD83 from PRRSV-infected MoDCs. The viral nonstructural protein 1 (Nsp1) is responsible for upregulating CD83 promoter activity. Amino acids in the ZF domain of Nsp1alpha (L5-2A, rG45A, G48A, and L61 6A) are essential for CD83 promoter activation. Viruses with mutations at these sites no longer inhibit MoDC-mediated T cell proliferation. These findings provide novel insights into the mechanism by which the adaptive immune response is suppressed during PRRSV infection. PMID- 29793956 TI - RESTRICTION OF gamma34.5-DELETED ONCOLYTIC HERPES SIMPLEX VIRUS REPLICATION IN GLIOBLASTOMA STEM-LIKE CELLS. AB - Oncolytic viruses, including herpes simplex viruses (HSVs), are a new class of cancer therapeutic engineered to infect and kill cancer cells, while sparing normal tissue. To ensure that oncolytic HSV (oHSV) is safe in the brain, all oHSVs in clinical trial for glioma lack the gamma34.5 genes responsible for neurovirulence. However, loss of gamma34.5 attenuates growth in cancer cells. Glioblastoma (GBM) is a lethal brain tumor that is heterogeneous and contains a subpopulation of cancer stem cells, termed GBM stem-like cells (GSCs), that likely promote tumor progression and recurrence. GSCs and matched serum-cultured GBM cells (ScGCs), representative of bulk or differentiated tumor cells, were isolated from the same patient tumor specimens. ScGCs are permissive to gamma34.5 deleted oHSV replication and cell killing, while patient-matched GSCs were not, implying an underlying biological difference between stem and bulk cancer cells. GSCs specifically restrict the synthesis of HSV1 true late (TL) proteins, without affecting viral DNA replication or transcription of TL genes. A global shutoff of cellular protein synthesis also occurs late after gamma34.5-deleted oHSV infection of GSCs, but does not affect the synthesis of early and leaky late viral proteins. Levels of phosphorylated eIF2alpha and eIF4E do not correlate with cell permissivity. Expression of Us11 in GSCs rescues replication of gamma34.5-deleted oHSV. The difference in permissivity between GSCs and ScGCs to gamma34.5-deleted oHSV illustrates a selective translational regulatory pathway in GSCs that may be operative in other stem-like cells and has implications for creating oHSVs.IMPORTANCE Herpes simplex virus (HSV) can be genetically engineered to endow cancer selective replication and oncolytic activity. gamma34.5, a key neurovirulence gene, has been deleted in all oncolytic HSVs in clinical trial for glioma. Glioblastoma stem-like cells (GSCs) are a subpopulation of tumor cells thought to drive tumor heterogeneity and therapeutic resistance. GSCs are non-permissive for gamma34.5-deleted HSV, while non-stem like cancer cells from the same patient tumors are permissive. GSCs restrict true late protein synthesis, despite normal viral DNA replication and transcription of all kinetic classes. This is specific for true late translation, as early and leaky late transcripts are translated late in infection, notwithstanding shutoff of cellular protein synthesis. Expression of Us11 in GSCs rescues the replication of gamma34.5-deleted HSV. We have identified a cell type specific innate response to HSV1 that limits oncolytic activity in glioblastoma. PMID- 29793960 TI - Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. PMID- 29793961 TI - Erratum. PMID- 29793959 TI - Defining the Role of Stress Granules in Innate Immune Suppression by the Herpes Simplex Virus 1 Endoribonuclease VHS. AB - In response to virus-induced shutoff host protein synthesis, dynamic aggregates containing mRNA, RNA-binding proteins and translation factors termed stress granules (SGs) often accumulate within the cytoplasm. SGs typically form following phosphorylation and inactivation of the eukaryotic translation initiation factor 2alpha (eIF2alpha), a substrate of the double-stranded RNA (dsRNA)-activated kinase protein kinase R (PKR). The detection of innate immune sensors and effectors like PKR at SGs suggests a role in pathogen nucleic acid sensing. However, the functional importance of SGs in host innate responses is unclear and has primarily been examined in response to infection with select RNA viruses. During infection with the DNA virus herpes simplex virus 1 (HSV-1), the virus-encoded virion host shutoff (VHS) endoribonuclease is required to restrict interferon production, PKR activation, and SG formation, although the relationship between these activities remains incompletely understood. Here, we show that in cells infected with a VHS-deficient HSV-1 (DeltaVHS) dsRNA accumulated and localized to SGs. Surprisingly, formation of dsRNA and its concentration at SGs was not required for beta interferon mRNA induction, indicating that suppression of type I interferon induction by VHS does not stem from its control of dsRNA accumulation. Instead, STING signaling downstream of cGMP-AMP synthase (cGAS)-dependent DNA sensing is required for beta interferon induction. In contrast, significantly less PKR activation is observed when SG assembly is disrupted by ISRIB, an inhibitor of phosphorylated eIF2alpha-mediated translation repression, or depleting SG scaffolding proteins G3BP1 or TIA1. This demonstrates that PKR activation is intimately linked to SG formation and that SGs form important hubs to potentiate PKR activation during infection.IMPORTANCE Formation of cytoplasmic stress granules that are enriched for innate immune sensors and effectors is suppressed during many viral infections. It is unclear, however, to what extent this is a side effect of viral efforts to maintain protein synthesis or intentional disruption of a hub for innate immune sensing. In this study, we utilize a herpes simplex virus 1 mutant lacking the RNA nuclease VHS which upon infection induces SGs, PKR activation, and beta interferon to address this question. We show that dsRNA is localized to SGs and that SGs can function to promote PKR activation in the context of a DNA virus infection, but we find no evidence to support their importance for interferon induction during HSV-1 infection. PMID- 29793962 TI - Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis. AB - Background Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established.Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30 day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan-Meier methods.Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in >=30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations.Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis. PMID- 29793957 TI - Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4 Based Adjuvants in Macaques. AB - We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIVmac251-based vaccine formulated with either of two Toll like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIVsmE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5alpha-resistant (TRIM-5alpha R) allele. Vaccinees were preferentially infected by an SIVsmE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIVsmE660 specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5alpha R and TRIM-5alpha-moderate/sensitive (TRIM-5alpha M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5alpha R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge.IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIVsmE660 acquisition, and genetic makeup (TRIM 5alpha) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms. PMID- 29793958 TI - SAMHD1 Impairs HIV-1 Gene Expression and Negatively Modulates Reactivation of Viral Latency in CD4+ T Cells. AB - Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (HIV-1) replication in nondividing cells by degrading intracellular deoxynucleoside triphosphates (dNTPs). SAMHD1 is highly expressed in resting CD4+ T cells, which are important for the HIV-1 reservoir and viral latency; however, whether SAMHD1 affects HIV-1 latency is unknown. Recombinant SAMHD1 binds HIV-1 DNA or RNA fragments in vitro, but the function of this binding remains unclear. Here we investigate the effect of SAMHD1 on HIV-1 gene expression and reactivation of viral latency. We found that endogenous SAMHD1 impaired HIV-1 long terminal repeat (LTR) activity in monocytic THP-1 cells and HIV-1 reactivation in latently infected primary CD4+ T cells. Overexpression of wild-type (WT) SAMHD1 suppressed HIV-1 LTR-driven gene expression at a transcriptional level. Tat coexpression abrogated SAMHD1-mediated suppression of HIV-1 LTR-driven luciferase expression. SAMHD1 overexpression also suppressed the LTR activity of human T-cell leukemia virus type 1 (HTLV-1), but not that of murine leukemia virus (MLV), suggesting specific suppression of retroviral LTR-driven gene expression. WT SAMHD1 bound to proviral DNA and impaired reactivation of HIV-1 gene expression in latently infected J-Lat cells. In contrast, a nonphosphorylated mutant (T592A) and a dNTP triphosphohydrolase (dNTPase) inactive mutant (H206D R207N [HD/RN]) of SAMHD1 failed to efficiently suppress HIV-1 LTR-driven gene expression and reactivation of latent virus. Purified recombinant WT SAMHD1, but not the T592A and HD/RN mutants, bound to fragments of the HIV-1 LTR in vitro These findings suggest that SAMHD1-mediated suppression of HIV-1 LTR-driven gene expression potentially regulates viral latency in CD4+ T cells.IMPORTANCE A critical barrier to developing a cure for HIV-1 infection is the long-lived viral reservoir that exists in resting CD4+ T cells, the main targets of HIV-1. The viral reservoir is maintained through a variety of mechanisms, including regulation of the HIV-1 LTR promoter. The host protein SAMHD1 restricts HIV-1 replication in nondividing cells, but its role in HIV-1 latency remains unknown. Here we report a new function of SAMHD1 in regulating HIV-1 latency. We found that SAMHD1 suppressed HIV-1 LTR promoter driven gene expression and reactivation of viral latency in cell lines and primary CD4+ T cells. Furthermore, SAMHD1 bound to the HIV-1 LTR in vitro and in a latently infected CD4+ T-cell line, suggesting that the binding may negatively modulate reactivation of HIV-1 latency. Our findings indicate a novel role for SAMHD1 in regulating HIV-1 latency, which enhances our understanding of the mechanisms regulating proviral gene expression in CD4+ T cells. PMID- 29793963 TI - A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease. AB - Background Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). We hypothesized that NOX4 derived H2O2 contributes to podocyte damage in DKD via elevation of podocyte calcium.Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SSNox4-/-) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6. We performed whole animal studies and used biosensor measurements, electron microscopy, electrophysiology, and live calcium imaging experiments to evaluate the contribution of this pathway to the physiology of the podocytes in freshly isolated glomeruli.Results Upon induction of type 1 diabetes with streptozotocin, SSNox4-/- rats exhibited significantly lower basal intracellular Ca2+ levels in podocytes and less DKD associated damage than SS rats did. Furthermore, the angiotensin II-elicited calcium flux was blunted in glomeruli isolated from diabetic SSNox4-/- rats compared with that in glomeruli from diabetic SS rats. H2O2 stimulated TRPC dependent calcium influx in podocytes from wild-type mice, but this influx was blunted in podocytes from Trpc6-knockout mice and, in a similar manner, in podocytes from Trpc5/6 double-knockout mice. Finally, electron microscopy revealed that podocytes of glomeruli isolated from Trpc6-knockout or Trpc5/6 double-knockout mice were protected from damage induced by H2O2 to the same extent.Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD. PMID- 29793964 TI - Clinical Characteristics and Outcome of Lung Transplant Recipients with Respiratory Isolation of Corynebacterium spp. AB - Although chronic respiratory disease and immunosuppression are risk factors for Corynebacterium species respiratory infection, data are scarce regarding this disease in lung transplantation. Our aim was to describe the clinical characteristics and outcomes of lung transplant recipients (LTR) with respiratory isolation of Corynebacterium spp. This was a retrospective observational study performed at a referral center in Barcelona, Spain (2014 to 2016). We included all LTR in whom Corynebacterium spp. were isolated in at least one good-quality lower respiratory tract specimen. Overall, 24 of 527 (4.6%) LTR at risk during the study period were included. The main epidemiological, clinical, and microbiological data were analyzed. The most frequently isolated species were C. striatum (11/24), C. pseudodiphtheriticum (3/24), and C. amycolatum (3/24). All 19 (76%) patients who underwent bronchoscopy showed abnormalities, mainly mucosal plaques at the bronchial suture and purulent secretions. Clinical cure was achieved in 8/12 (67%) patients who fulfilled the CDC definition of lower respiratory tract infection (LRTI). To assess the clinical relevance of Corynebacterium spp., only patients with monomicrobial isolation (n = 18) were evaluated. LRTI was diagnosed in 9, and a nonsignificant association was found with a significant number of Corynebacterium sp. CFU/ml (7/9 LRTI versus 2/9 non LRTI, P = 0.057). Persistent infection was associated with metallic bronchial stent implantation (4/4 versus 2/14, P = 0.005). The isolation of Corynebacterium spp. in respiratory specimens of lung transplant recipients may herald a respiratory tract infection or bronchial suture damage. Bronchial stent implantation is a risk factor for the persistence of Corynebacterium species infection. PMID- 29793965 TI - Evaluation of Performance Characteristics of Panther Fusion Assays for Detection of Respiratory Viruses from Nasopharyngeal and Lower Respiratory Tract Specimens. AB - Accurate and rapid diagnosis is needed for timely intervention and clinical management of acute respiratory infections. This study evaluated performance characteristics of the Panther Fusion assay for the detection of influenza A virus (Flu A), influenza B virus (Flu B), respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3 (Para 1 to 3), human metapneumovirus (hMPV), rhinovirus (RV), and adenovirus (Adeno) targets in comparison to those of the eSensor and Lyra assays using 395 nasopharyngeal (NP) and 104 lower respiratory tract (LRT) specimens. Based on the consensus positive result established (positive result in 2 of the 3 assays), the NP specimens for the Fusion and eSensor assays had 100% positive percent agreement (PPA) for all the analytes and the Lyra assays had 100% PPA for Flu A and Adeno analytes. A 100% negative percent agreement (NPA) was observed for all the Lyra analytes, whereas those for the Fusion targets ranged from 98.4 to 100% and those for the eSensor ranged from 99.4 to 100% for all the analytes except RV. For the LRT specimens, Fusion had 100% PPA and 100% NPA for all the targets except hMPV. There was a 100% PPA for eSensor analytes; the NPA ranged from 98 to 100%, except for RV. For the Lyra assays, the PPA ranged between 50 and 100%, while the NPA was 100% for all the targets except Adeno. The Fusion assay performed similarly to the eSensor assay for majority of the targets tested and provides laboratories with a fully automated random-access system to test for a broad array of viral respiratory pathogens. PMID- 29793966 TI - QuantiFERON-TB Gold Plus Is a More Sensitive Screening Tool than QuantiFERON-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facilities. AB - We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon gamma release assays, i.e., QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient positive, and negative results from QFTs during reproducibility analysis were classified as definite, possible, and not LTBI, respectively). Two hundred forty four residents were enrolled, and 229 subjects were included in the analysis. The median age was 80 years (range, 60 to 102 years old), and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results from QFT-GIT and QFT-Plus, respectively, and the results for 215 (93.9%) subjects showed agreement. Using the composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible, and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%, respectively. The sensitivity of QFT-GIT decreased gradually with patient age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% versus 89.4%, P = 0.013) and similar specificity (95.1% versus 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs. PMID- 29793967 TI - Diagnostic Performance of Pleural Fluid Adenosine Deaminase for Tuberculous Pleural Effusion in a Low-Incidence Setting. AB - The challenges associated with diagnosing tuberculous pleural effusion have led to the use of pleural fluid adenosine deaminase (pfADA) as a biomarker for Mycobacterium tuberculosis infection. This study retrospectively reviewed the diagnostic performance of pfADA, the pleural fluid lactate dehydrogenase (LD)/ADA ratio, and combinations of these two parameters in 1,637 episodes of pleural effusion in the low-tuberculosis (TB)-incidence setting of Auckland, Aotearoa New Zealand, from between March 2008 and November 2014. The median pfADA in 57 TB pleural effusion episodes (58.1 U/liter) was significantly higher (P < 0.001) than in 1,580 non-TB pleural effusions (11.4 U/liter). The median LD/ADA ratio in TB pleural effusion (8.2) was significantly lower (P < 0.001) than in non-TB pleural effusions (30.5). The pfADA and pleural fluid LD/ADA ratio AUCROC values (that is, receiver operating characteristic [ROC] curve analysis with determination of the ROC area under the curve) were 0.93 and 0.94, respectively. The pfADA thresholds of >=15 and >=30 U/liter demonstrated sensitivities of 100% (95% confidence internal = 93.7 to 100) and 93.0% (83.3 to 97.2), specificities of 62.7% (60.3 to 65.0) and 87.3% (85.6 to 88.9), positive predictive values (PPVs) of 8.8% (6.9 to 11.2) and 20.9% (16.4 to 26.4), and negative predictive values (NPVs) of 100% (99.6 to 100) and 99.7% (99.3 to 99.9), respectively. LD/ADA ratio thresholds of <25 and <15 demonstrated sensitivities of 100% (93.5 to 100) and 89.1% (78.2 to 94.9), specificities of 61.6% (59.1 to 64.0) and 84.8% (82.9 to 86.5), PPVs of 8.5% (6.6 to 10.9) and 17.3% (13.3 to 22.0), and NPVs of 100% (99.6 to 100) and 99.5% (99.0 to 99.8), respectively. A combination of pfADA >= 30 U/liter and an LD/ADA ratio < 15 increased the specificity and PPV to 97.8% (96.9 to 98.4) and 57.3% (46.5 to 67.5) but decreased the sensitivity to 85.5% (73.8 to 92.4). The primary value of pfADA in a low-TB-incidence setting, such as Auckland, is in utilization of its high NPV. PMID- 29793970 TI - Effects of mindfulness training programmes delivered by a self-directed mobile app and by telephone compared with an education programme for survivors of critical illness: a pilot randomised clinical trial. AB - BACKGROUND: Patients who are sick enough to be admitted to an intensive care unit (ICU) commonly experience symptoms of psychological distress after discharge, yet few effective therapies have been applied to meet their needs. METHODS: Pilot randomised clinical trial with 3-month follow-up conducted at two academic medical centres. Adult (>=18 years) ICU patients treated for cardiorespiratory failure were randomised after discharge home to 1 of 3 month-long interventions: a self-directed mobile app-based mindfulness programme; a therapist-led telephone based mindfulness programme; or a web-based critical illness education programme. RESULTS: Among 80 patients allocated to mobile mindfulness (n=31), telephone mindfulness (n=31) or education (n=18), 66 (83%) completed the study. For the primary outcomes, target benchmarks were exceeded by observed rates for all participants for feasibility (consent 74%, randomisation 91%, retention 83%), acceptability (mean Client Satisfaction Questionnaire 27.6 (SD 3.8)) and usability (mean Systems Usability Score 89.1 (SD 11.5)). For secondary outcomes, mean values (and 95% CIs) reflected clinically significant group-based changes on the Patient Health Questionnaire depression scale (mobile (-4.8 (-6.6, -2.9)), telephone (-3.9 (-5.6, -2.2)), education (-3.0 (-5.3, 0.8)); the Generalized Anxiety Disorder scale (mobile -2.1 (-3.7, -0.5), telephone -1.6 (-3.0, -0.1), education -0.6 (-2.5, 1.3)); the Post-Traumatic Stress Scale (mobile -2.6 (-6.3, 1.2), telephone -2.2 (-5.6, 1.2), education -3.5 (-8.0, 1.0)); and the Patient Health Questionnaire physical symptom scale (mobile -5.3 (-7.0, -3.7), telephone 3.7 (-5.2, 2.2), education -4.8 (-6.8, 2.7)). CONCLUSIONS: Among ICU patients, a mobile mindfulness app initiated after hospital discharge demonstrated evidence of feasibility, acceptability and usability and had a similar impact on psychological distress and physical symptoms as a therapist-led programme. A larger trial is warranted to formally test the efficacy of this approach. TRIAL REGISTRATION NUMBER: Results, NCT02701361. PMID- 29793968 TI - Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates. AB - Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next generation assays. Three-hundred-member panels of 20 serially diluted well characterized antibody-negative HIV isolates for which the researchers were blind to the results (blind panels) were distributed to manufacturers and end-user labs to assess the relative analytic sensitivity of currently approved and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays for the detection of diverse subtypes. The limits of detection (LODs) of virus were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blind panel. On the basis of the proportion of positive results on 300 observations, all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo assays performed poorly. The similar performance of the different commercially available fourth generation assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next generation preclinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while rapid fourth-generation assays performed poorly for p24 Ag detection. PMID- 29793969 TI - Clinical Pharmacogenomics: Applications in Nephrology. AB - Pharmacogenomics is a tool for practitioners to provide precision pharmacotherapy using genomics. All providers are likely to encounter genomic data in practice with the expectation that they are able to successfully apply it to patient care. Pharmacogenomics tests for genetic variations in genes that are responsible for drug metabolism, transport, and targets of drug action. Variations can increase the risk for drug toxicity or poor efficacy. Pharmacogenomics can, therefore, be used to help select the best medication or aid in dosing. Nephrologists routinely treat cardiovascular disease and manage patients after kidney transplantation, two situations for which there are several high-evidence clinical recommendations for commonly used anticoagulants, antiplatelets, statins, and transplant medications. Successful use of pharmacogenomics in practice requires that providers are familiar with how to access and use pharmacogenomics resources. Similarly, clinical decision making related to whether to use existing data, whether to order testing, and if data should be used in practice is needed to deliver precision medicine. Pharmacogenomics is applicable to virtually every medical specialty, and nephrologists are well positioned to be implementation leaders. PMID- 29793973 TI - Cortical Oscillatory Mechanisms Supporting the Control of Human Social-Emotional Actions. AB - The human anterior prefrontal cortex (aPFC) is involved in regulating social emotional behavior, presumably by modulating effective connectivity with downstream parietal, limbic, and motor cortices. Regulating that connectivity might rely on theta-band oscillations (4-8 Hz), a brain rhythm known to create overlapping periods of excitability between distant regions by temporally releasing neurons from inhibition. Here, we used MEG to understand how aPFC theta band oscillations implement control over prepotent social-emotional behaviors; that is, the control over automatically elicited approach and avoidance actions. Forty human male participants performed a social approach-avoidance task in which they approached or avoided visually displayed emotional faces (happy or angry) by pulling or pushing a joystick. Approaching angry and avoiding happy faces (incongruent condition) requires rapid application of cognitive control to override prepotent habitual action tendencies to approach appetitive and to avoid aversive situations. In the time window before response delivery, trial-by-trial variations in aPFC theta-band power (6 Hz) predicted reaction time increases during emotional control and were inversely related to beta-band power (14-22 Hz) over parietofrontal cortex. In sensorimotor areas contralateral to the moving hand, premovement gamma-band rhythms (60-90 Hz) were stronger during incongruent than congruent trials, with power increases phase locked to peaks of the aPFC theta-band oscillations. These findings define a mechanistic relation between cortical areas involved in implementing rapid control over human social-emotional behavior. The aPFC may bias neural processing toward rule-driven actions and away from automatic emotional tendencies by coordinating tonic disinhibition and phasic enhancement of parietofrontal circuits involved in action selection.SIGNIFICANCE STATEMENT Being able to control social-emotional behavior is crucial for successful participation in society, as is illustrated by the severe social and occupational difficulties experienced by people suffering from social motivational disorders such as social anxiety. In this study, we show that theta-band oscillations in the anterior prefrontal cortex (aPFC), which are thought to provide temporal organization for neural firing during communication between distant brain areas, facilitate this control by linking aPFC to parietofrontal beta-band and sensorimotor gamma-band oscillations involved in action selection. These results contribute to a mechanistic understanding of cognitive control over automatic social-emotional action and point to frontal theta-band oscillations as a possible target of rhythmic neurostimulation techniques during treatment for social anxiety. PMID- 29793971 TI - Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury. AB - Autophagy mechanisms are well documented in neurons after spinal cord injury (SCI), but the direct functional role of autophagy in oligodendrocyte (OL) survival in SCI pathogenesis remains unknown. Autophagy is an evolutionary conserved lysosomal-mediated catabolic pathway that ensures degradation of dysfunctional cellular components to maintain homeostasis in response to various forms of stress, including nutrient deprivation, hypoxia, reactive oxygen species, DNA damage, and endoplasmic reticulum (ER) stress. Using pharmacological gain and loss of function and genetic approaches, we investigated the contribution of autophagy in OL survival and its role in the pathogenesis of thoracic contusive SCI in female mice. Although upregulation of Atg5 (an essential autophagy gene) occurs after SCI, autophagy flux is impaired. Purified myelin fractions of contused 8 d post-SCI samples show enriched protein levels of LC3B, ATG5, and BECLIN 1. Data show that, while the nonspecific drugs rapamycin (activates autophagy) and spautin 1 (blocks autophagy) were pharmacologically active on autophagy in vivo, their administration did not alter locomotor recovery after SCI. To directly analyze the role of autophagy, transgenic mice with conditional deletion of Atg5 in OLs were generated. Analysis of hindlimb locomotion demonstrated a significant reduction in locomotor recovery after SCI that correlated with a greater loss in spared white matter. Immunohistochemical analysis demonstrated that deletion of Atg5 from OLs resulted in decreased autophagic flux and was detrimental to OL function after SCI. Thus, our study provides evidence that autophagy is an essential cytoprotective pathway operating in OLs and is required for hindlimb locomotor recovery after thoracic SCI.SIGNIFICANCE STATEMENT This study describes the role of autophagy in oligodendrocyte (OL) survival and pathogenesis after thoracic spinal cord injury (SCI). Modulation of autophagy with available nonselective drugs after thoracic SCI does not affect locomotor recovery despite being pharmacologically active in vivo, indicating significant off-target effects. Using transgenic mice with conditional deletion of Atg5 in OLs, this study definitively identifies autophagy as an essential homeostatic pathway that operates in OLs and exhibits a direct functional role in SCI pathogenesis and recovery. Therefore, this study emphasizes the need to discover novel autophagy-specific drugs that specifically modulate autophagy for further investigation for clinical translation to treat SCI and other CNS pathologies related to OL survival. PMID- 29793972 TI - Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus. AB - Astrocyte-derived factors can control synapse formation and functions, making astrocytes an attractive target for regulating neuronal circuits and associated behaviors. Abnormal astrocyte-neuronal interactions are also implicated in neurodevelopmental disorders and neurodegenerative diseases associated with impaired learning and memory. However, little is known about astrocyte-mediated mechanisms that regulate learning and memory. Here, we propose astrocytic ephrin B1 as a regulator of synaptogenesis in adult hippocampus and mouse learning behaviors. We found that astrocyte-specific ablation of ephrin-B1 in male mice triggers an increase in the density of immature dendritic spines and excitatory synaptic sites in the adult CA1 hippocampus. However, the prevalence of immature dendritic spines is associated with decreased evoked postsynaptic firing responses in CA1 pyramidal neurons, suggesting impaired maturation of these newly formed and potentially silent synapses or increased excitatory drive on the inhibitory neurons resulting in the overall decreased postsynaptic firing. Nevertheless, astrocyte-specific ephrin-B1 knock-out male mice exhibit normal acquisition of fear memory but enhanced contextual fear memory recall. In contrast, overexpression of astrocytic ephrin-B1 in the adult CA1 hippocampus leads to the loss of dendritic spines, reduced excitatory input, and impaired contextual memory retention. Our results suggest that astrocytic ephrin-B1 may compete with neuronal ephrin-B1 and mediate excitatory synapse elimination through its interactions with neuronal EphB receptors. Indeed, a deletion of neuronal EphB receptors impairs the ability of astrocytes expressing functional ephrin-B1 to engulf synaptosomes in vitro Our findings demonstrate that astrocytic ephrin-B1 regulates long-term contextual memory by restricting new synapse formation in the adult hippocampus.SIGNIFICANCE STATEMENT These studies address a gap in our knowledge of astrocyte-mediated regulation of learning and memory by unveiling a new role for ephrin-B1 in astrocytes and elucidating new mechanisms by which astrocytes regulate learning. Our studies explore the mechanisms underlying astrocyte regulation of hippocampal circuit remodeling during learning using new genetic tools that target ephrin-B signaling in astrocytes in vivo On a subcellular level, astrocytic ephrin-B1 may compete with neuronal ephrin-B1 and trigger astrocyte-mediated elimination of EphB receptor containing synapses. Given the role EphB receptors play in neurodevelopmental disorders and neurodegenerative diseases, these findings establish a foundation for future studies of astrocyte-mediated synaptogenesis in clinically relevant conditions that can help to guide the development of clinical applications for a variety of neurological disorders. PMID- 29793974 TI - Classification of Neurons in the Primate Reticular Formation and Changes after Recovery from Pyramidal Tract Lesion. AB - The reticular formation is important in primate motor control, both in health and during recovery after brain damage. Little is known about the different neurons present in the reticular nuclei. Here we recorded extracellular spikes from the reticular formation in five healthy female awake behaving monkeys (193 cells), and in two female monkeys 1 year after recovery from a unilateral pyramidal tract lesion (125 cells). Analysis of spike shape and four measures derived from the interspike interval distribution identified four clusters of neurons in control animals. Cluster 1 cells had a slow firing rate. Cluster 2 cells had narrow spikes and irregular firing, which often included high-frequency bursts. Cluster 3 cells were highly rhythmic and fast firing. Cluster 4 cells showed negative spikes. A separate population of 42 cells was antidromically identified as reticulospinal neurons in five anesthetized female monkeys. The distribution of spike width in these cells closely overlaid the distribution for cluster 2, leading us tentatively to suggest that cluster 2 included neurons with reticulospinal projections. In animals after corticospinal lesion, cells could be identified in all four clusters. The firing rate of cells in clusters 1 and 2 was increased in lesioned animals relative to control animals (by 52% and 60%, respectively); cells in cluster 2 were also more regular and more bursting in the lesioned animals. We suggest that changes in both membrane properties and local circuits within the reticular formation occur following lesioning, potentially increasing reticulospinal output to help compensate for lost corticospinal descending drive.SIGNIFICANCE STATEMENT This work is the first to subclassify neurons in the reticular formation, providing insights into the local circuitry of this important but little understood structure. The approach developed can be applied to any extracellular recording from this region, allowing future studies to place their data within our current framework of four neural types. Changes in reticular neurons may be important to subserve functional recovery after damage in human patients, such as after stroke or spinal cord injury. PMID- 29793977 TI - The Interplay Between Spike-Time and Spike-Rate Modes in the Auditory Nerve Encodes Tone-In-Noise Threshold. AB - Auditory nerve fibers (ANFs) encode pure tones through two modes of coding, spike time and spike rate, depending on the tone frequency. In response to a low frequency tone, ANF firing is phase locked to the sinusoidal waveform. Because time coding vanishes with an increase in the tone frequency, high-frequency tone coding relies on the spike rate of the ANFs. Adding a continuous broadband noise to a tone compresses the rate intensity function of ANFs and shifts its dynamic range toward higher intensities. Therefore, the ANFs with high-threshold/low spontaneous rate (SR) are thought to contribute to behavioral tone detection in noise. However, this theory relies on the discharge rate of the ANFs. The direct comparison with the masking threshold through spike timing, irrespective of the spontaneous rate, has not so far been investigated. Taking advantage of a unique proxy to quantify the spike synchrony (i.e., the shuffle autocorrelogram), we show in female gerbils that high-SR ANFs are more adapted to encode low-frequency thresholds through temporal code, giving them a strong robustness in noise. By comparing behavioral thresholds measured using prepulse inhibition of the acoustical startle reflex with population thresholds calculated from ANFs pooled per octave band, we show that threshold-based spike timing provides a better estimate of behavioral thresholds in the low-frequency range, whereas the high frequency behavioral thresholds rely on the spiking rate, particularly in noise. This emphasizes the complementarity of temporal and rate modes to code tone-in noise thresholds over a large range of frequencies.SIGNIFICANCE STATEMENT There is a general agreement that high-threshold/low-spontaneous rate (SR) auditory nerve fibers (ANFs) are of prime importance for tone detection in noise. However, this theory is based on the discharge rate of the fibers. Comparing the behavioral thresholds and single ANF thresholds shows that this is only true in the high-frequency range of tone stimulations. In the low-frequency range of tones (up to 2.7 kHz in the gerbil), the most sensitive ANFs (high-SR fibers) carry neural information through a spike-timing mode, even for noise in which tones do not induce a noticeable increment in the spike rate. This emphasizes the interplay between spike-time and spike-rate modes in the auditory nerve to encode tone-in-noise threshold over a large range of tone frequencies. PMID- 29793975 TI - Preferential Targeting of Lateral Entorhinal Inputs onto Newly Integrated Granule Cells. AB - Mature dentate granule cells in the hippocampus receive input from the entorhinal cortex via the perforant path in precisely arranged lamina, with medial entorhinal axons innervating the middle molecular layer and lateral entorhinal cortex axons innervating the outer molecular layer. Although vastly outnumbered by mature granule cells, adult-generated newborn granule cells play a unique role in hippocampal function, which has largely been attributed to their enhanced excitability and plasticity (Schmidt-Hieber et al., 2004; Ge et al., 2007). Inputs from the medial and lateral entorhinal cortex carry different informational content. Thus, the distribution of inputs onto newly integrated granule cells will affect their function in the circuit. Using retroviral labeling in combination with selective optogenetic activation of medial or lateral entorhinal inputs, we examined the functional innervation and synaptic maturation of newly generated dentate granule cells in the mouse hippocampus. Our results indicate that lateral entorhinal inputs provide the majority of functional innervation of newly integrated granule cells at 21 d postmitosis. Despite preferential functional targeting, the dendritic spine density of immature granule cells was similar in the outer and middle molecular layers, which we speculate could reflect an unequal distribution of shaft synapses. However, chronic blockade of neurotransmitter release of medial entorhinal axons with tetanus toxin disrupted normal synapse development of both medial and lateral entorhinal inputs. Our results support a role for preferential lateral perforant path input onto newly generated neurons in mediating pattern separation, but also indicate that medial perforant path input is necessary for normal synaptic development.SIGNIFICANCE STATEMENT The formation of episodic memories involves the integration of contextual and spatial information. Newly integrated neurons in the dentate gyrus of the hippocampus play a critical role in this process, despite constituting only a minor fraction of the total number of granule cells. Here we demonstrate that these neurons preferentially receive information thought to convey the context of an experience. Each newly integrated granule cell plays this unique role for ~1 month before reaching maturity. PMID- 29793976 TI - nox2/cybb Deficiency Affects Zebrafish Retinotectal Connectivity. AB - NADPH oxidase (Nox)-derived reactive oxygen species (ROS) have been linked to neuronal polarity, axonal outgrowth, cerebellar development, regeneration of sensory axons, and neuroplasticity. However, the specific roles that individual Nox isoforms play during nervous system development in vivo remain unclear. To address this problem, we investigated the role of Nox activity in the development of retinotectal connections in zebrafish embryos. Zebrafish broadly express four nox genes (nox1, nox2/cybb, nox5, and duox) throughout the CNS during early development. Application of a pan-Nox inhibitor, celastrol, during the time of optic nerve (ON) outgrowth resulted in significant expansion of the ganglion cell layer (GCL), thinning of the ON, and a decrease in retinal axons reaching the optic tectum (OT). With the exception of GCL expansion, these effects were partially ameliorated by the addition of H2O2, a key ROS involved in Nox signaling. To address isoform-specific Nox functions, we used CRISPR/Cas9 to generate mutations in each zebrafish nox gene. We found that nox2/cybb chimeric mutants displayed ON thinning and decreased OT innervation. Furthermore, nox2/cybb homozygous mutants (nox2/cybb-/-) showed significant GCL expansion and mistargeted retinal axons in the OT. Neurite outgrowth from cultured zebrafish retinal ganglion cells was reduced by Nox inhibitors, suggesting a cell autonomous role for Nox in these neurons. Collectively, our results show that Nox2/Cybb is important for retinotectal development in zebrafish.SIGNIFICANCE STATEMENT Most isoforms of NADPH oxidase (Nox) only produce reactive oxygen species (ROS) when activated by an upstream signal, making them ideal candidates for ROS signaling. Nox enzymes are present in neurons and their activity has been shown to be important for neuronal development and function largely by in vitro studies. However, whether Nox is involved in the development of axons and formation of neuronal connections in vivo has remained unclear. Using mutant zebrafish embryos, this study shows that a specific Nox isoform, Nox2/Cybb, is important for the establishment of axonal connections between retinal ganglion cells and the optic tectum. PMID- 29793978 TI - Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation. AB - Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia.SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia. PMID- 29793979 TI - Deep Neural Networks for Modeling Visual Perceptual Learning. AB - Understanding visual perceptual learning (VPL) has become increasingly more challenging as new phenomena are discovered with novel stimuli and training paradigms. Although existing models aid our knowledge of critical aspects of VPL, the connections shown by these models between behavioral learning and plasticity across different brain areas are typically superficial. Most models explain VPL as readout from simple perceptual representations to decision areas and are not easily adaptable to explain new findings. Here, we show that a well -known instance of deep neural network (DNN), whereas not designed specifically for VPL, provides a computational model of VPL with enough complexity to be studied at many levels of analyses. After learning a Gabor orientation discrimination task, the DNN model reproduced key behavioral results, including increasing specificity with higher task precision, and also suggested that learning precise discriminations could transfer asymmetrically to coarse discriminations when the stimulus conditions varied. Consistent with the behavioral findings, the distribution of plasticity moved toward lower layers when task precision increased and this distribution was also modulated by tasks with different stimulus types. Furthermore, learning in the network units demonstrated close resemblance to extant electrophysiological recordings in monkey visual areas. Altogether, the DNN fulfilled predictions of existing theories regarding specificity and plasticity and reproduced findings of tuning changes in neurons of the primate visual areas. Although the comparisons were mostly qualitative, the DNN provides a new method of studying VPL, can serve as a test bed for theories, and assists in generating predictions for physiological investigations.SIGNIFICANCE STATEMENT Visual perceptual learning (VPL) has been found to cause changes at multiple stages of the visual hierarchy. We found that training a deep neural network (DNN) on an orientation discrimination task produced behavioral and physiological patterns similar to those found in human and monkey experiments. Unlike existing VPL models, the DNN was pre-trained on natural images to reach high performance in object recognition, but was not designed specifically for VPL; however, it fulfilled predictions of existing theories regarding specificity and plasticity and reproduced findings of tuning changes in neurons of the primate visual areas. When used with care, this unbiased and deep-hierarchical model can provide new ways of studying VPL from behavior to physiology. PMID- 29793980 TI - Calciprotein Particle Formation in Peritoneal Dialysis Effluent Is Dependent on Dialysate Calcium Concentration. AB - BACKGROUND: The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo. METHOD: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. RESULTS: High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo, compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. CONCLUSION: High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design. PMID- 29793981 TI - Expanding CAPD in Low-Resource Settings: A Distance Learning Approach. AB - BACKGROUND: Despite growing need, treatment for end-stage renal disease is limited in low- and middle-income countries due to resource restraints. We describe the development of an educational curriculum and quality improvement program to support continuous ambulatory peritoneal dialysis (CAPD) performed primarily by non-nephrology providers in Sri Lanka. METHODS: We developed a program of education, outcome tracking, and expert consultation to support providers in Kandy, Sri Lanka. Education included videos and in-person didactics covering core topics in CAPD. Event-tracking sheets recorded root causes and management of infections and hospitalizations. Conferences reviewed clinical cases and overall clinic management. We evaluated the patient census, peritonitis rates, and root causes and management of infections over 1 year. RESULTS: The curriculum was published through the International Society of Nephrology online academy. High provider turnover limited curriculum assessments. The CAPD patient census rose from 63 to 116 during the year. The peritonitis rate declined significantly, from 0.8 episodes per patient-year in the first 6 months to 0.4 in the latter 6 months, though the most common root causes of peritonitis, related to contamination events and hygiene, persisted. The appropriate ascertainment of culture data and prescription of antibiotics also increased. CONCLUSIONS: Our project supported the expansion of a CAPD program in a resource-limited setting, while also improving peritonitis outcomes. Ongoing challenges include ensuring a durable educational system for rotating providers, tracking outcomes beyond peritonitis, and formalizing management protocols. Our program can serve as an example of how established dialysis programs can support the burgeoning work of providers in resource-limited setting. PMID- 29793983 TI - Heartbeat: socioeconomic deprivation is associated with non-cardiovascular mortality in chronic heart failure patients. PMID- 29793984 TI - Miscellaneous: Secondary mitral regurgitation: pathophysiology, diagnosis, and treatment. PMID- 29793982 TI - Peritoneal Dialysis for AKI in Cameroon: Commercial vs Locally-Made Solutions. AB - BACKGROUND: Acute kidney injury (AKI) is common in low- and middle-income countries, and is associated with a high mortality. The high mortality rate is in large part due to the inability to perform dialysis in resource-limited settings. Due to significant cost advantages, peritoneal dialysis (PD) has been used to treat AKI in these settings. The costs, however, remain high when commercial solutions are used. METHODS: This is a retrospective cohort study of the outcome, and of the peritonitis rates, of patients with AKI treated with either commercially manufactured PD solutions or locally-made PD solutions. A program to treat AKI with PD was started at Mbingo Baptist Hospital in Cameroon. Between May 2013 and January 2015, solutions and connection sets were provided by the Saving Young Lives Program. From January 2015 through March 2017, solutions were locally produced and available tubing was used. RESULTS: Mortality in hospitalized AKI patients was 28% during the period when commercial solutions and tubing were utilized, and 33% when locally produced solutions and available tubing were utilized. In both groups, peritonitis occurred in 16% of treatment courses. CONCLUSIONS: Locally produced PD solutions, used with locally available tubing, were used to treat AKI with PD. The mortality and peritonitis rates were similar whether locally produced or commercial supplies were used. PMID- 29793985 TI - Advocating for Life Support Training of Children, Parents, Caregivers, School Personnel, and the Public. AB - Pediatric cardiac arrest in the out-of-hospital setting is a traumatic event for family, friends, caregivers, classmates, and school personnel. Immediate bystander cardiopulmonary resuscitation and the use of automatic external defibrillators have been shown to improve survival in adults. There is some evidence to show improved survival in children who receive immediate bystander cardiopulmonary resuscitation. Pediatricians, in their role as advocates to improve the health of all children, are uniquely positioned to strongly encourage the training of children, parents, caregivers, school personnel, and the lay public in the provision of basic life support, including pediatric basic life support, as well as the appropriate use of automated external defibrillators. PMID- 29793986 TI - Outpatient Antibiotic Use and the Need for Increased Antibiotic Stewardship Efforts. AB - Antibiotic-resistant infections pose a growing threat to public health. Antibiotic use, regardless of whether it is warranted, is a primary factor in the development of resistance. In the United States, the majority of antibiotic health care expenditures are due to prescribing in outpatient settings. Much of this prescribing is inappropriate, with research showing that at least 30% of antibiotic use in outpatient settings is unnecessary. In this State of the Art Review article, we provide an overview of the latest research on outpatient antibiotic prescribing practices in the United States. Although many of the researchers in these studies describe antibiotic prescribing across all patient age groups, we highlight prescribing in pediatric populations when data are available. We then describe the various factors that can influence a physician's prescribing decisions and drive inappropriate antibiotic use and the potential role of behavioral science in enhancing stewardship interventions to address these drivers. Finally, we highlight the role that a wide range of health care stakeholders can play in aiding the expansion of outpatient stewardship efforts that are needed to fully address the threat of antibiotic resistance. PMID- 29793987 TI - Advocating for Life Support Training of Children, Parents, Caregivers, School Personnel, and the Public. AB - Out-of-hospital cardiac arrest occurs frequently among people of all ages, including more than 6000 children annually. Pediatric cardiac arrest in the out of-hospital setting is a stressful event for family, friends, caregivers, classmates, school personnel, and witnesses. Immediate bystander cardiopulmonary resuscitation and the use of automated external defibrillators are associated with improved survival in adults. There is some evidence in which improved survival in children who receive immediate bystander cardiopulmonary resuscitation is shown. Pediatricians, in their role as advocates to improve the health of all children, are uniquely positioned to strongly encourage the training of children, parents, caregivers, school personnel, and the lay public in the provision of basic life support, including pediatric basic life support, as well as the appropriate use of automated external defibrillators. PMID- 29793989 TI - Myocardial Bridge and the Progression of Atherosclerotic Plaque in the Proximal Segment. PMID- 29793988 TI - Telomerase: Location, Location, Location? PMID- 29793990 TI - Proteases, Protease-Activated Receptors, and Atherosclerosis. PMID- 29793991 TI - Smooth Muscle Cells Move With Mitochondria. PMID- 29793993 TI - Letter by Rus et al Regarding Article, "RGC-32 (Response Gene to Complement 32) Deficiency Protects Endothelial Cells From Inflammation and Attenuates Atherosclerosis". PMID- 29793995 TI - Letter by Ramirez and Hibbert Regarding Article, "Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the Arteriosclerosis, Thrombosis, and Vascular Biology Council". PMID- 29793992 TI - Thrombotic Regulation From the Endothelial Cell Perspectives. PMID- 29793996 TI - Response by Daugherty et al to Letter Regarding Article, "Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the Arteriosclerosis, Thrombosis, and Vascular Biology Council". PMID- 29793994 TI - Response by Cui et al to Letter Regarding Article, "RGC-32 (Response Gene to Complement 32) Deficiency Protects Endothelial Cells From Inflammation and Attenuates Atherosclerosis". PMID- 29793997 TI - Antidepressant utilisation and incidence of weight gain during 10 years' follow up: population based cohort study. AB - OBJECTIVE: To evaluate the long term association between antidepressant prescribing and body weight. DESIGN: Population based cohort study. SETTING: General practices contributing to the UK Clinical Practice Research Datalink, 2004-14. PARTICIPANTS: 136 762 men and 157 957 women with three or more records for body mass index (BMI). MAIN OUTCOME MEASURES: The main outcomes were antidepressant prescribing, incidence of >=5% increase in body weight, and transition to overweight or obesity. Adjusted rate ratios were estimated from a Poisson model adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking, and advice on diet. RESULTS: In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of >=5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of >=5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations. CONCLUSION: Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated. PMID- 29793998 TI - UK government vows to adopt stringent WHO clean air targets. PMID- 29793999 TI - The Transplantation of omega3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild Type Littermates Prevents Obesity and Associated Metabolic Disorders. AB - Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of omega3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of omega3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the omega3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype. PMID- 29794002 TI - Dyslipidaemia and cardiovascular risk. PMID- 29794001 TI - Skin specialist is suspended for six months after secretly recording colleague's consultations. PMID- 29794003 TI - Atopic eczema and cardiovascular disease. PMID- 29794000 TI - Observe Before You Leap: Why Observation Provides Critical Insights for Formative Research and Intervention Design That You'll Never Get From Focus Groups, Interviews, or KAP Surveys. AB - Formative research is essential to designing both study instruments and interventions in global health. While formative research may employ many qualitative methods, focus group discussions and in-depth interviews are the most common. Observation is less common but can generate insights unlikely to emerge from any other method. This article presents 4 case studies in which observation revealed critical insights: corralling domestic poultry to reduce childhood diarrhea, promoting insecticide-treated bed nets (ITNs) to prevent malaria, evaluating skilled birth attendant competency to manage life-threatening obstetric and neonatal complications, and assessing community health worker (CHW) ability to use malaria rapid diagnostic tests (RDTs). Observation of Zambian CHWs to design malaria RDT training materials revealed a need for training on how to take finger-stick blood samples, a procedure second nature to many health workers but one that few CHWs had ever performed. In Lima, Peru, study participants reported keeping their birds corralled "all the time," but observers frequently found them loose, a difference potentially explained by an alternative interpretation of the phrase "all the time" to mean "all the time (except at some specific seemingly obvious times)." In the Peruvian Amazon, observation revealed a potential limitation of bed net efficacy due to the built environment: In houses constructed on stilts, many people sleep directly on the floor, allowing mosquitoes to bite from below through gaps in the floorboards. Observation forms and checklists from each case study are included as supplemental files; these may serve as models for designing new observation guides. The case studies illustrate the value of observation to clearly understanding clinical practices and skills, details about how people carry out certain tasks, routine behaviors people would most likely not think to describe in an interview, and environmental barriers that must be overcome if an intervention is to succeed. Observation provides a way to triangulate for social desirability bias and to measure details that interview or focus group participants are unlikely to recognize, remember, or be able to describe with precision. PMID- 29794004 TI - Role of the light source position in freely falling hoverflies' stabilization performances. AB - The stabilization of plummeting hoverflies was filmed and analysed in terms of their wingbeat initiation times as well as the crash and stabilization rates. The flies experienced near-weightlessness for a period of time that depended on their ability to counteract the free fall by triggering their wingbeats. In this paradigm, hoverflies' flight stabilization strategies were investigated here for the first time under two different positions of the light source (overhead and bottom lighting). The crash rates were higher in bottom lighting conditions than with top lighting. In addition, adding a texture to the walls reduced the crash rates only in the overhead lighting condition. The position of the lighting also significantly affected both the stabilization rates and the time taken by the flies to stabilize, which decreased and increased under bottom lighting conditions, respectively, whereas textured walls increased the stabilization rates under both lighting conditions. These results support the idea that flies may mainly base their flight control strategy on visual cues and particularly that the light distribution in the visual field may provide reliable, efficient cues for estimating their orientation with respect to an allocentric reference frame. In addition, the finding that the hoverflies' optic flow-based motion detection ability is affected by the position of the light source in their visual field suggests the occurrence of interactions between movement perception and this visual vertical perception process. PMID- 29794005 TI - Non-uniform evolutionary response of gecko eye size to changes in diel activity patterns. AB - Geckos feature a large range of eye sizes, but what drives this phenotypic diversity is currently unknown. Earlier studies point towards diel activity patterns (DAPs) and locomotory mode, but phylogenetic comparative studies in support of the proposed adaptive mode of eye evolution are lacking. Here, we test the hypothesis of DAPs as the driver of eye size evolution with a dataset on 99 species of gecko. Results from phylogenetic generalized least-square analysis (PGLS) and multivariate model-fitting reveal smaller eyes in diurnal geckos consistent with different phenotypic optima. However, Bayesian analyses of selective regime shifts demonstrate that only two of nine transitions from nocturnal to diurnal activity are coupled with decreases in eye size, and two other regime shifts are not associated with DAP transitions. This non-uniform evolutionary response suggests that eye size is not the only functionally relevant variable. Evolutionary adaptations may therefore include different combinations of several traits (e.g. photoreceptors), all with the same functional outcome. Our results further demonstrate that DAP only partially explains eye size diversity in geckos. As open habitats favour the evolution of large eyes while obstructed habitats favour small eyes, the degree of habitat clutter emerges as another potential axis of eye diversification. PMID- 29794006 TI - The origin of the bird's beak: new insights from dinosaur incubation periods. AB - The toothless beak of modern birds was considered as an adaption for feeding ecology; however, several recent studies suggested that developmental factors are also responsible for the toothless beak. Neontological and palaeontological studies have progressively uncovered how birds evolved toothless beaks and suggested that the multiple occurrences of complete edentulism in non-avian dinosaurs were the result of selection for specialized diets. Although developmental biology and ecological factors are not mutually exclusive, the conventional hypothesis that ecological factors account for the toothless beak appears insufficient. A recent study on dinosaur incubation period using embryonic teeth posited that tooth formation rate limits developmental speed, constraining toothed dinosaur incubation to slow reptilian rates. We suggest that selection for tooth loss was a side effect of selection for fast embryo growth and thus shorter incubation. This observation would also explain the multiple occurrences of tooth loss and beaks in non-avian dinosaur taxa crownward of Tyrannosaurus Whereas our hypothesis is an observation without any experimental supports, more studies of gene regulation of tooth formation in embryos would allow testing for the trade-off between incubation period and tooth development. PMID- 29794008 TI - Evidence for contrasting roles for prolactin in eusocial naked mole-rats, Heterocephalus glaber and Damaraland mole-rats, Fukomys damarensis. AB - Elevated prolactin (PRL) has been associated with the expression of social and cooperative behaviours in a number of vertebrate species, as well as suppression of reproduction. As social mole-rats exhibit both of these traits, PRL is a prime candidate in mediating their social phenotype. While naked and Damaraland mole rats (NMRs and DMRs) have evolved eusociality independently within their family, both species exhibit an extreme skew in lifetime reproductive success, with breeding restricted to a single female and one or two males. Non-breeding NMRs of both sexes are physiologically inhibited from reproducing, while in DMRs only the non-breeding females are physiologically suppressed. Newly emerging work has implicated the dopamine system and PRL as a component in socially induced reproductive suppression and eusociality in NMR, but the DMR remains unstudied in this context. To investigate evolutionary convergence in the role of PRL in shaping African mole-rat eusociality, we determined plasma PRL concentrations in breeders and non-breeders of both sexes, comparing DMRs with NMRs. Among samples from non-breeding NMRs 80% had detectable plasma PRL concentrations. As a benchmark, these often (37%) exceeding those considered clinically hyperprolactinaemic (25 ng ml-1) in humans: mean +/- s.e.m.: 34.81 +/- 5.87 ngml 1; range 0.00-330.30 ng ml-1 Conversely, 85% of non-breeding DMR samples had undetectable values and none had concentrations above 25 ng ml-1: 0.71 +/- 0.38 ng ml-1; 0.00-23.87 ngml-1 Breeders in both species had the expected variance in plasma PRL concentrations as part of normal reproductive function, with lactating queens having significantly higher values. These results suggest that while elevated PRL in non-breeders is implicated in NMR eusociality, this may not be the case in DMRs, and suggests a lack of evolutionary convergence in the proximate control of the social phenotype in these mole-rats. PMID- 29794007 TI - Simultaneous radiation of bird and mammal lice following the K-Pg boundary. AB - The diversification of parasite groups often occurs at the same time as the diversification of their hosts. However, most studies demonstrating this concordance only examine single host-parasite groups. Multiple diverse lineages of ectoparasitic lice occur across both birds and mammals. Here, we describe the evolutionary history of lice based on analyses of 1107 single-copy orthologous genes from sequenced genomes of 46 species of lice. We identify three major diverse groups of lice: one exclusively on mammals, one almost exclusively on birds and one on both birds and mammals. Each of these groups radiated just after the Cretaceous-Paleogene (K-Pg) boundary, the time of the mass extinction event of the dinosaurs and rapid diversification of most of the modern lineages of birds and mammals. PMID- 29794009 TI - Spatial spread of Wolbachia in Rhagoletis cerasi populations. AB - The bacterial endosymbiont Wolbachia has been used to control insect pests owing to its ability to manipulate their life history and suppress infectious diseases. Therefore, knowledge on Wolbachia dynamics in natural populations is fundamental. The European cherry fruit fly, Rhagoletis cerasi, is infected with the Wolbachia strain wCer2, mainly present in southern and central European populations, and is currently spreading into wCer2-uninfected populations driven by high unidirectional cytoplasmic incompatibility. Here, we describe the distribution of wCer2 along two transition zones where the infection is spreading into wCer2 uninfected R. cerasi populations. Fine-scale sampling of 19 populations in the Czech Republic showed a smooth decrease of wCer2 frequency from south to north within a distance of less than 20 km. Sampling of 12 Hungarian populations, however, showed a sharp decline of wCer2 infection frequency within a few kilometres. We fitted a standard wave equation to our empirical data and estimated a Wolbachia wave speed of 1.9 km yr-1 in the Czech Republic and 1.0 km yr-1 in Hungary. Considering the univoltine life cycle and limited dispersal ability of R. cerasi, our study highlights a rapid Wolbachia spread in natural host populations. PMID- 29794010 TI - Neuromyelitis optica spectrum disorder presenting as rhomboencephalitis. AB - Rhomboencephalitis, at least in its acute phase, is often a severely disabling syndrome, and can be life threatening. A range of underlying conditions can lead to this clinical syndrome. Rapid diagnosis to initiate treatment early is key to a beneficial outcome. We report the case of a 22 year old Afro-Caribbean woman, who presented with a two -week history of walking difficulties, upper limb incoordination and slurred speech. Her brainstem function deteriorated at pace, and she developed hypersomnia. A broad diagnostic approach led to prophylactic treatment for the most common infectious causes. This did not improve her symptoms. Non-infectious inflammatory causes were therefore considered and plasma exchange treatment was initiated leading to marked improvement within days. Screening for autoimmune conditions confirmed aquaporin-4 positive neuromyelitis optica spectrum disorder (NMOSD) as the underlying cause. Immunotherapy with rituximab was started. So far, no relapse has been observed. While the definition of NMOSD continues to be refined, aquaporin-4 testing should be considered early in patients presenting with rhomboencephalitis who do not respond to antibiotic and antiviral treatment. Vigilance and early intervention are key to limit morbidity and mortality from NMOSD. PMID- 29794011 TI - Spontaneous acalculous gallbladder perforation post-cardiac transplantation. AB - Spontaneous acalculous gallbladder perforation is a rare radiological and clinical phenomenon with life-threatening consequences. In the setting of recent cardiac transplantation, the condition is increasingly uncommon and difficult to diagnose preoperatively. We describe a case of spontaneous acalculous gallbladder perforation in an intensive care unit (ICU) patient, most likely due to a combination of cardiac transplantation and immunosuppression. There are no such documented cases in the literature with an established preoperative diagnosis, to the best of our knowledge. Abdominal CT and targeted ultrasound proved complimentary in establishing the diagnosis, facilitating successful and timely treatment with urgent cholecystectomy. PMID- 29794012 TI - Stuck guidewire due to soft tissue imposition: a rare complication of central line catheter placement. AB - Central venous catheter (CVC) placement is a commonly done procedure but is associated with a few complications, and guidewire-related complications are one of them. In our case after induction of general anaesthesia, we planned to insert a CVC in the right internal jugular vein under ultrasound guidance. After the insertion of the introducer needle, when we tried to insert the guidewire, it got stuck and was neither moving forward nor in a backward direction. Too much force was not applied to remove the guidewire as it might have caused shearing of the guidewire and further complicated the picture. This problem was solved by simultaneous withdrawal of guidewire along with the needle, and on examination we found soft tissue debris lodged within the lumen which was preventing the guidewire movement in both directions. So, it is suggested that guidewire should be removed along with needle as a single unit if it is required. PMID- 29794013 TI - Transcription Factor NFAT5 Promotes Migration and Invasion of Rheumatoid Synoviocytes via Coagulation Factor III and CCL2. AB - Fibroblast-like synoviocytes (FLSs) play a key role in the progression of rheumatoid arthritis (RA) as a primary component of invasive hypertrophied pannus. FLSs of RA patients (RA-FLSs) exhibit cancer-like features, including promigratory and proinvasive activities that largely contribute to joint cartilage and bone destruction. In this study, we hypothesized that the NF of activated T cell 5 (NFAT5), a transcription factor involving tumor invasiveness, would control the migration and invasion of RA-FLSs. Analyses of transcriptomes demonstrated the significant involvement of NFAT5 in locomotion of RA-FLSs and that tissue factor (TF; also known as coagulation factor III) and CCL2 were the major downstream target genes of NFAT5 involving FLS migration and invasion. In cultured RA-FLSs, IL-1beta and TGF-beta increased TF and CCL2 expression by upregulating NFAT5 expression via p38 MAPK. Functional assays demonstrated that NFAT5- or TF-deficient RA-FLSs displayed decreased lamellipodia formation, cell migration, and invasion under IL-1beta- or TGF-beta-stimulated conditions. Conversely, factor VIIa, a specific activator of TF, increased migration of RA FLSs, which was blocked by NFAT5 knockdown. Recombinant CCL2 partially restored the decrease in migration and invasion of NFAT5-deficient RA-FLSs stimulated with IL-1beta. NFAT5-knockout mouse FLSs also showed decreased expressions of TF and CCL2 and reduced cell migration. Moreover, KRN2, a specific inhibitor of NFAT5, suppressed migration of FLSs stimulated with TGF-beta. Conclusively, to our knowledge, this is the first study to provide evidence of a functional link between osmoprotective NFAT5 and TF in the migration and invasion of RA-FLSs and supports a role for NFAT5 blockade in the treatment of RA. PMID- 29794015 TI - Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation. AB - There is cross-talk between the intestinal epithelium and the microbiota that functions to maintain a tightly regulated microenvironment and prevent chronic inflammation. This communication is partly mediated through the recognition of bacterial proteins by host-encoded innate receptors, such as TLRs. However, studies examining the role of TLR signaling on colonic homeostasis have given variable and conflicting results. Despite its critical role in mediating immunity during enteric infection of the small intestine, TLR1-mediated recognition of microbiota-derived ligands and their influence on colonic homeostasis has not been well studied. In this study, we demonstrate that defective TLR1 recognition of the microbiome by epithelial cells results in disruption of crypt homeostasis specifically within the secretory cell compartment, including a defect in the mucus layer, ectopic Paneth cells in the colon, and an increase in the number of rapidly dividing cells at the base of the crypt. As a consequence of the perturbed epithelial barrier, we found an increase in mucosal-associated and translocated commensal bacteria and chronic low-grade inflammation characterized by an increase in lineage-negative Sca1+Thy1hi innate lymphoid-like cells that exacerbate inflammation and worsen outcomes in a model of colonic injury and repair. Our findings demonstrate that sensing of the microbiota by TLR1 may provide key signals that regulate the colonic epithelium, thereby limiting inflammation through the prevention of bacterial attachment to the mucosa and exposure to the underlying immune system. PMID- 29794016 TI - IL-36alpha from Skin-Resident Cells Plays an Important Role in the Pathogenesis of Imiquimod-Induced Psoriasiform Dermatitis by Forming a Local Autoamplification Loop. AB - IL-36alpha (gene symbol Il1f6), a member of the IL-36 family, is closely associated with inflammatory diseases, including colitis and psoriasis. In this study, we found that Il1f6-/- mice developed milder psoriasiform dermatitis upon treatment with imiquimod, a ligand for TLR ligand 7 (TLR7) and TLR8, whereas Il1f6-/- mice showed similar susceptibility to dextran sodium sulfate-induced colitis to wild-type mice. These effects were observed in both cohoused and separately housed conditions, and antibiotic treatment did not cancel the resistance of Il1f6-/- mice to imiquimod-induced dermatitis. Bone marrow (BM) cell transfer revealed that IL-36alpha expression in skin-resident cells is important for the pathogenesis of dermatitis in these mice. Following stimulation with IL-36alpha, the expression of Il1f6 and Il1f9 (IL-36gamma), but not Il1f8 (IL-36beta), was enhanced in murine BM-derived Langerhans cells (BMLCs) and murine primary keratinocytes but not in fibroblasts from mice. Upon stimulation with agonistic ligands of TLRs and C-type lectin receptors (CLRs), Il1f6 expression was induced in BMLCs and BM-derived dendritic cells. Furthermore, IL 36alpha stimulation resulted in significantly increased gene expression of psoriasis-associated Th17-related cytokines and chemokines such as IL-1alpha, IL 1beta, IL-23, CXCL1, and CXCL2 in BMLCs and fibroblasts, and IL-1alpha, IL-1beta, IL-17C, and CXCL2 in keratinocytes. Collectively, these results suggest that TLR/CLR signaling-induced IL-36alpha plays an important role for the development of psoriasiform dermatitis by enhancing Th17-related cytokine/chemokine production in skin-resident cells via a local autoamplification loop. PMID- 29794014 TI - PRMT1 Plays a Critical Role in Th17 Differentiation by Regulating Reciprocal Recruitment of STAT3 and STAT5. AB - Th17 cells are a class of Th cells that secrete IL-17 and mediate pathogenic immunity responsible for autoimmunity including experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Retinoic acid-related orphan receptor gamma t (RORgammat) is the critical transcription factor that controls the differentiation of Th17 cells. However, little is known about the transcriptional cofactors for RORgammat in the regulation of Th17 differentiation. In this study, we demonstrate that protein arginine N methyltransferase 1 (PRMT1) associates with RORgammat and regulates mouse Th17 differentiation. Overexpression of PRMT1 promoted Th17 differentiation, whereas inactivation or knockdown of PRMT1 decreased Th17 differentiation while expanding Foxp3+ regulatory T cells. Consistently, pharmacological inhibition of PRMT1 impaired the generation of Th17 cells and prevented induction of experimental autoimmune encephalomyelitis in mice. Mechanistically, PRMT1-dependent modification of asymmetric histone 4 arginine 3 dimethylation is required to stabilize the stimulatory STAT3 to displace the inhibitory STAT5 at IL-17 locus, resulting in the activation of IL-17 gene. Furthermore, PRMT1-facilitated recruitment of STAT3 overcame the inhibition of Th17 differentiation exerted by IL-2-induced STAT5 activation. PRMT1 thus regulates Th17 differentiation by controlling the reciprocal recruitment of STAT3 and STAT5. Our study thus reveals PRMT1 as a novel target for alleviating Th17-mediated autoimmunity by decreasing RORgammat-dependent generation of pathogenic Th17 cells. PMID- 29794017 TI - Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to Substance P, Hemokinin-1, Human beta Defensin-3, and Icatibant. AB - Human mast cells (MCs) express a novel G protein-coupled receptor (GPCR) known as Mas-related GPCR X2 (MRGPRX2). Activation of this receptor by a diverse group of cationic ligands such as neuropeptides, host defense peptides, and Food and Drug Administration-approved drugs contributes to chronic inflammatory diseases and pseudoallergic drug reactions. For most GPCRs, the extracellular (ECL) domains and their associated transmembrane (TM) domains display the greatest structural diversity and are responsible for binding different ligands. The goal of the current study was to determine if naturally occurring missense variants within MRGPRX2's ECL/TM domains contribute to gain or loss of function phenotype for MC degranulation in response to neuropeptides (substance P and hemokinin-1), a host defense peptide (human beta-defensin-3) and a Food and Drug Administration approved cationic drug (bradykinin B2 receptor antagonist, icatibant). We have identified eight missense variants within MRGPRX2's ECL/TM domains from publicly available exome-sequencing databases. We investigated the ability of MRGPRX2 ligands to induce degranulation in rat basophilic leukemia-2H3 cells individually expressing these naturally occurring MRGPRX2 missense variants. Using stable and transient transfections, we found that all variants express in rat basophilic leukemia cells. However, four natural MRGPRX2 variants, G165E (rs141744602), D184H (rs372988289), W243R (rs150365137), and H259Y (rs140862085) failed to respond to any of the ligands tested. Thus, diverse MRGPRX2 ligands use common sites on the receptor to induce MC degranulation. These findings have important clinical implications for MRGPRX2 and MC-mediated pseudoallergy and chronic inflammatory diseases. PMID- 29794018 TI - The Extra-Pathway Interactome of the TCA Cycle: Expected and Unexpected Metabolic Interactions. AB - The plant tricarboxylic acid (TCA) cycle provides essential precursors for respiration, amino acid biosynthesis, and general nitrogen metabolism; moreover, it is closely involved in biotic stress responses and cellular redox homeostasis. To further understand the in vivo function of the TCA cycle enzymes, we combined affinity purification with proteomics to generate a comprehensive extra-pathway protein-protein interaction network of the plant TCA cycle. We identified 125 extra-pathway interactions in Arabidopsis (Arabidopsis thaliana) mostly related to the mitochondrial electron transport complex/ATP synthesis and amino acid metabolism but also to proteins associated with redox stress. We chose three high scoring and two low-scoring interactions for complementary bimolecular fluorescence complementation and yeast two-hybrid assays, which highlighted the reliability of our approach, supported the intimate involvement of TCA cycle enzymes within many biological processes, and reflected metabolic changes reported previously for the corresponding mutant lines. To analyze the function of a subset of these interactions, we selected two mutants of mitochondrial glutaredoxin S15 and Amidase, which have not yet been analyzed with respect to their TCA cycle function, and performed metabolite profiling and flux analysis. Consistent with their interactions identified in this study, TCA cycle metabolites and the relative TCA flux of the two mutants were altered significantly. PMID- 29794019 TI - NLR Mutations Suppressing Immune Hybrid Incompatibility and Their Effects on Disease Resistance. AB - Genetic divergence between populations can lead to reproductive isolation. Hybrid incompatibilities (HI) represent intermediate points along a continuum toward speciation. In plants, genetic variation in disease resistance (R) genes underlies several cases of HI. The progeny of a cross between Arabidopsis (Arabidopsis thaliana) accessions Landsberg erecta (Ler, Poland) and Kashmir2 (Kas2, central Asia) exhibits immune-related HI. This incompatibility is due to a genetic interaction between a cluster of eight TNL (TOLL/INTERLEUKIN1 RECEPTOR NUCLEOTIDE BINDING-LEU RICH REPEAT) RPP1 (RECOGNITION OF PERONOSPORA PARASITICA1) like genes (R1-R8) from Ler and central Asian alleles of a Strubbelig-family receptor-like kinase (SRF3) from Kas2. In characterizing mutants altered in Ler/Kas2 HI, we mapped multiple mutations to the RPP1-like Ler locus. Analysis of these suppressor of Ler/Kas2 incompatibility (sulki) mutants reveals complex, additive and epistatic interactions underlying RPP1-like Ler locus activity. The effects of these mutations were measured on basal defense, global gene expression, primary metabolism, and disease resistance to a local Hyaloperonospora arabidopsidis isolate (Hpa Gw) collected from Gorzow (Gw), where the Landsberg accession originated. Gene expression sectors and metabolic hallmarks identified for HI are both dependent and independent of RPP1-like Ler members. We establish that mutations suppressing immune-related Ler/Kas2 HI do not compromise resistance to Hpa Gw. QTL mapping analysis of Hpa Gw resistance point to RPP7 as the causal locus. This work provides insight into the complex genetic architecture of the RPP1-like Ler locus and immune-related HI in Arabidopsis and into the contributions of RPP1-like genes to HI and defense. PMID- 29794021 TI - Glycolate Induces Redox Tuning Of Photosystem II in Vivo: Study of a Photorespiration Mutant. AB - Bicarbonate removal from the nonheme iron at the acceptor side of photosystem II (PSII) was shown recently to shift the midpoint potential of the primary quinone acceptor QA to a more positive potential and lowers the yield of singlet oxygen (1O2) production. The presence of QA- results in weaker binding of bicarbonate, suggesting a redox-based regulatory and protective mechanism where loss of bicarbonate or exchange of bicarbonate by other small carboxylic acids may protect PSII against 1O2 in vivo under photorespiratory conditions. Here, we compared the properties of QA in the Arabidopsis (Arabidopsis thaliana) photorespiration mutant deficient in peroxisomal HYDROXYPYRUVATE REDUCTASE1 (hpr1 1), which accumulates glycolate in leaves, with the wild type. Photosynthetic electron transport was affected in the mutant, and chlorophyll fluorescence showed slower electron transport between QA and QB in the mutant. Glycolate induced an increase in the temperature maximum of thermoluminescence emission, indicating a shift of the midpoint potential of QA to a more positive value. The yield of 1O2 production was lowered in thylakoid membranes isolated from hpr1-1 compared with the wild type, consistent with a higher potential of QA/QA- In addition, electron donation to photosystem I was affected in hpr1-1 at higher light intensities, consistent with diminished electron transfer out of PSII. This study indicates that replacement of bicarbonate at the nonheme iron by a small carboxylate anion occurs in plants in vivo. These findings suggested that replacement of the bicarbonate on the nonheme iron by glycolate may represent a regulatory mechanism that protects PSII against photooxidative stress under low CO2 conditions. PMID- 29794022 TI - YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6. AB - RATIONALE: Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium play a critical role in the pathophysiology of sepsis and organ failure. The intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood. OBJECTIVE: To determine the central role of YAP (Yes-associated protein), the major transcriptional coactivator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation. METHODS AND RESULTS: Endothelial-specific YAP knockout mice showed increased basal expression of E-selectin and ICAM (intercellular adhesion molecule)-1 in endothelial cells, a greater number of adherent neutrophils in postcapillary venules and increased neutrophil counts in bronchoalveolar lavage fluid. Lipopolysaccharide challenge of these mice augmented NF-kappaB (nuclear factor-kappaB) activation, expression of endothelial adhesion proteins, neutrophil and monocyte adhesion to cremaster muscle venules, transendothelial neutrophil migration, and lung inflammatory injury. Deletion of YAP in endothelial cells also markedly augmented the inflammatory response and cardiovascular dysfunction in a polymicrobial sepsis model induced by cecal ligation and puncture. YAP functioned by interacting with the E3 ubiquitin protein ligase TLR (Toll-like receptor) signaling adaptor TRAF6 (tumor necrosis factor receptor-associated factor 6) to ubiquitinate TRAF6, and thus promoted TRAF6 degradation and modification resulting in inhibition of NF-kappaB activation. TRAF6 depletion in endothelial cells rescued the augmented inflammatory phenotype in mice with endothelial cell-specific deletion of YAP. CONCLUSIONS: YAP modulates the activation of endothelial cells and suppresses vascular inflammation through preventing TRAF6-mediated NF-kappaB activation and is hence essential for limiting the severity of sepsis-induced inflammation and organ failure. PMID- 29794025 TI - Trump's proposals would restrict US abortions and deny sexual health services for millions. PMID- 29794024 TI - Reproductive performance of male mice after hypothalamic ghrelin administration. AB - It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (GHRL) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of GHRL action mechanism on the reproductive system has not been fully elucidated, we studied the participation of hypothalamus in GHRL effects on sperm functional activity, plasma levels of gonadotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day GHRL or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that GHRL 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (GHRL 3.0 nmol/day = 14.05 +/- 2.44 * 106/mL vs ACSF = 20.33 +/- 1.35 * 106/mL, P < 0.05) and motility (GHRL 3.0 nmol/day = 59.40 +/- 4.20% vs ACSF = 75.80 +/- 1.40%, P < 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (GHRL 3.0 nmol/day = 6.76 +/- 0.68% vs ACSF = 9.56 +/- 0.41%, P < 0.05) and sperm (GHRL 3.0 nmol/day = 24.24 +/- 1.92% vs ACSF = 31.20 +/- 3.06%, P < 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (P < 0.05). As GHRL is an orexigenic peptide, body weight and food intake were measured. Results showed that GHRL increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central GHRL administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis. PMID- 29794020 TI - Decoys Untangle Complicated Redundancy and Reveal Targets of Circadian Clock F Box Proteins. AB - Eukaryotic circadian clocks utilize the ubiquitin proteasome system to precisely degrade clock proteins. In plants, the F-box-type E3 ubiquitin ligases ZEITLUPE (ZTL), FLAVIN-BINDING, KELCH REPEAT, F-BOX1 (FKF1), and LOV KELCH PROTEIN2 (LKP2) regulate clock period and couple the clock to photoperiodic flowering in response to end-of-day light conditions. To better understand their functions, we expressed decoy ZTL, FKF1, and LKP2 proteins that associate with target proteins but are unable to ubiquitylate their targets in Arabidopsis (Arabidopsis thaliana). These dominant-negative forms of the proteins inhibit the ubiquitylation of target proteins and allow for the study of ubiquitylation independent and -dependent functions of ZTL, FKF1, and LKP2. We demonstrate the effects of expressing ZTL, FKF1, and LKP2 decoys on the circadian clock and flowering time. Furthermore, the decoy E3 ligases trap substrate interactions, and using immunoprecipitation-mass spectrometry, we identify interacting partners. We focus studies on the clock transcription factor CCA1 HIKING EXPEDITION (CHE) and show that ZTL interacts directly with CHE and can mediate CHE ubiquitylation. We also demonstrate that CHE protein is degraded in the dark and that degradation is reduced in a ztl mutant plant, showing that CHE is a bona fide ZTL target protein. This work increases our understanding of the genetic and biochemical roles for ZTL, FKF1, and LKP2 and also demonstrates an effective methodology for studying complicated genetic redundancy among E3 ubiquitin ligases. PMID- 29794023 TI - Regulation of the porcine corpus luteum during pregnancy. AB - The new corpora lutea (CLs) in pigs are formed from the preovulatory follicles after the luteinizing hormone (LH) surge. However, total autonomy and independence of CLs from LH up to Day 12 of cycle has recently been questioned. Transformation of estrous cycle CL to CL of pregnancy initiated by embryonic signals requires not only the cessation of prostaglandin F2 (PGF2alpha) supply to the luteal tissue but also needs the CL to overcome luteolytic acquisition and/or changing its sensitivity to PGF2alpha during Days 12-14 of pregnancy. The luteolytic cascade is prevented by inhibition of lymphocyte infiltration and leucocyte recruitment, limitation of cell apoptosis, upregulation of pregnancy associated genes and an enhanced antiluteolytic role of PGE2 Our 'two-signal switch hypothesis' highlights the importance of post PGF2alpha and PGE2 receptor signaling pathways activation in CLs during luteolysis and rescue. The 'luteolytic switch' involves increased expression of many regression mediators and activation of the post PTGFR signaling pathway. The 'rescue switch' initiated by embryonic signals - estradiol 17beta and PGE2 - induces post PTGER2/4 pathway, turning the 'luteolytic switch' off and triggering activity of genes responsible for CL maintenance. In mid and late pregnancy, CLs are maintained by LH and the synergistic action of metabolic hormones. This paper provides an outline of recent views on CL regression, rescue and maintenance during pregnancy in pigs that conflict with previous paradigms and highlights new findings regarding the actions of prostaglandins, role of microRNAs (miRNA) and immune system and signaling pathways governing the life cycle of porcine CL. PMID- 29794026 TI - Protein kinase Calpha drives fibroblast activation and kidney fibrosis by stimulating autophagic flux. AB - Kidney fibrosis is a histological hallmark of chronic kidney disease and arises in large part through extracellular matrix deposition by activated fibroblasts. The signaling protein complex mTOR complex 2 (mTORC2) plays a critical role in fibroblast activation and kidney fibrosis. Protein kinase Calpha (PKCalpha) is one of the major sub-pathways of mTORC2, but its role in fibroblast activation and kidney fibrosis remains to be determined. Here, we found that transforming growth factor beta1 (TGFbeta1) activates PKCalpha signaling in cultured NRK-49F cells in a time-dependent manner. Blocking PKCalpha signaling with the chemical inhibitor Go6976 or by transfection with PKCalpha siRNA largely reduced expression of the autophagy-associated protein lysosomal-associated membrane protein 2 (LAMP2) and also inhibited autophagosome-lysosome fusion and autophagic flux in the cells. Similarly to chloroquine, Go6976 treatment and PKCalpha siRNA transfection also markedly inhibited TGFbeta1-induced fibroblast activation. In murine fibrotic kidneys with unilateral ureteral obstruction (UUO) nephropathy, PKCalpha signaling is activated in the interstitial myofibroblasts. Go6976 administration largely blocked autophagic flux in fibroblasts in the fibrotic kidneys and attenuated the UUO nephropathy. Together, our findings suggest that blocking PKCalpha activity may retard autophagic flux and thereby prevent fibroblast activation and kidney fibrosis. PMID- 29794027 TI - Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic insights into the differences in substrate specificity within the PPEP family. AB - Pro-Pro endopeptidases (PPEPs) belong to a recently discovered family of proteases capable of hydrolyzing a Pro-Pro bond. The first member from the bacterial pathogen Clostridium difficile (PPEP-1) cleaves two C. difficile cell surface proteins involved in adhesion, one of which is encoded by the gene adjacent to the ppep-1 gene. However, related PPEPs may exist in other bacteria and may shed light on substrate specificity in this enzyme family. Here, we report on the homolog of PPEP-1 in Paenibacillus alvei, which we denoted PPEP-2. We found that PPEP-2 is a secreted metalloprotease, which likewise cleaved a cell surface protein encoded by an adjacent gene. However, the cleavage motif of PPEP 2, PLP?PVP, is distinct from that of PPEP-1 (VNP?PVP). As a result, an optimal substrate peptide for PPEP-2 was not cleaved by PPEP-1 and vice versa. To gain insight into the specificity mechanism of PPEP-2, we determined its crystal structure at 1.75 A resolution and further confirmed the structure in solution using small-angle X-ray scattering (SAXS). We show that a four-amino-acid loop, which is distinct in PPEP-1 and -2 (GGST in PPEP-1 and SERV in PPEP-2), plays a crucial role in substrate specificity. A PPEP-2 variant, in which the four loop residues had been swapped for those from PPEP-1, displayed a shift in substrate specificity toward PPEP-1 substrates. Our results provide detailed insights into the PPEP-2 structure and the structural determinants of substrate specificity in this new family of PPEP proteases. PMID- 29794030 TI - What is this thing called injury prevention? PMID- 29794028 TI - Structural basis of transcriptional regulation by CouR, a repressor of coumarate catabolism, in Rhodopseudomonas palustris. AB - The MarR family transcriptional regulator CouR, from the soil bacterium Rhodopseudomonas palustris CGA009, has recently been shown to negatively regulate a p-coumarate catabolic operon. Unlike most characterized MarR repressors that respond to small metabolites at concentrations in the millimolar range, repression by CouR is alleviated by the 800-Da ligand p-coumaroyl-CoA with high affinity and specificity. Here we report the crystal structures of ligand-free CouR as well as the complex with p-coumaroyl-CoA, each to 2.1-A resolution, and the 2.85-A resolution cocrystal structure of CouR bound to an oligonucleotide bearing the cognate DNA operator sequence. In combination with binding experiments that uncover specific residues important for ligand and DNA recognition, these structures provide glimpses of a MarR family repressor in all possible states, providing an understanding of the molecular basis of DNA binding and the conformation alterations that accompany ligand-induced dissociation for activation of the operon. PMID- 29794029 TI - Chemoproteomics of matrix metalloproteases in a model of cartilage degeneration suggests functional biomarkers associated with posttraumatic osteoarthritis. AB - Active matrix metalloproteases (MMPs) play a significant role in the pathogenesis of many diseases including osteoarthritis (OA), which involves progressive proteolytic degradation of cartilage. Clinical success of OA interventions that target MMPs has been limited by a lack of information about the presence and activity of specific disease-related proteases. We therefore developed a chemoproteomics approach based on MS to characterize the release and activity of MMPs in an in vitro model of the early inflammatory phase of posttraumatic OA (PTOA). We designed and synthesized chemical activity-based probes (ABPs) to identify active MMPs in bovine cartilage explants cultured for 30 days with the proinflammatory cytokine, interleukin-1alpha. Using these probes in an activity based protein profiling-multidimensional identification technology (ABPP-MudPIT) approach, we identified active MMP-1, -2, -3, -7, -9, -12, and -13 in the medium after 10 days of culture, the time at which irreversible proteolysis of the collagen network in the explant was detected using proteolytic activation of FRET quenched MMP substrates. Total MMP levels were quantified by shotgun proteomics, which, taken with ABPP-MudPIT data, indicated the presence of predominantly inactive MMPs in the culture medium. The selectivity of the ABPP-MudPIT approach was further validated by detection of specific endogenous MMPs activated de novo with 4-aminophenylmurcuric acetate. The utility of the new ABPP-MudPIT approach for detecting molecular biomarkers of PTOA disease initiation and potential targets for therapeutics motivates possible application in other diseases involving MMP activity. PMID- 29794031 TI - Microtubules grow by the addition of bent guanosine triphosphate tubulin to the tips of curved protofilaments. AB - We used electron tomography to examine microtubules (MTs) growing from pure tubulin in vitro as well as two classes of MTs growing in cells from six species. The tips of all these growing MTs display bent protofilaments (PFs) that curve away from the MT axis, in contrast with previously reported MTs growing in vitro whose tips are either blunt or sheetlike. Neither high pressure nor freezing is responsible for the PF curvatures we see. The curvatures of PFs on growing and shortening MTs are similar; all are most curved at their tips, suggesting that guanosine triphosphate-tubulin in solution is bent and must straighten to be incorporated into the MT wall. Variations in curvature suggest that PFs are flexible in their plane of bending but rigid to bending out of that plane. Modeling by Brownian dynamics suggests that PF straightening for MT growth can be achieved by thermal motions, providing a simple mechanism with which to understand tubulin polymerization. PMID- 29794034 TI - Brexit is bad for our health. PMID- 29794035 TI - Comparison of Acute Ischemic Stroke Care and Outcomes Between Comprehensive Stroke Centers and Primary Stroke Centers in the United States. AB - BACKGROUND: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. This study aimed to compare ischemic stroke care and in-hospital outcomes between CSCs and PSCs. METHODS AND RESULTS: We analyzed patients with acute ischemic stroke who were hospitalized at stroke centers participating in Get With The Guidelines-Stroke from 2013 to 2015. Multivariable logistic regression models were generated to examine the association between stroke center certification (CSC versus PSC) and performances and outcomes. This study included 722 941 patients who were admitted to 134 CSCs and 1047 PSCs. Both CSCs and PSCs had good conformity to 7 performance measures and the summary defect-free care measure. Among emergency department admissions, CSCs had higher intravenous tPA (tissue-type plasminogen activator) and endovascular thrombectomy rates than PSCs (14.3% versus 10.3%, 4.1% versus 1.0%, respectively). Door to intravenous tPA time was shorter at CSCs (median, 52 versus 61 minutes; adjusted risk ratio, 0.92; 95% confidence interval, 0.89-0.95). More patients at CSCs had door to intravenous tPA time <=60 minutes (79.7% versus 65.1%; adjusted odds ratio, 1.48; 95% confidence interval, 1.25-1.75). For transferred patients, CSCs and PSCs had comparable overall performance in defect-free care, except higher endovascular thrombectomy therapy rates. The overall in-hospital mortality was higher at CSCs in both emergency department admissions (4.6% versus 3.8%; adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.29) and transferred patients (7.7% versus 6.8%; adjusted odds ratio, 1.17; 95% confidence interval, 1.05-1.32). In-hospital outcomes were comparable between CSCs and PSCs in patients who received intravenous tPA or endovascular thrombectomy. CONCLUSIONS: CSCs and PSCs achieved similar overall care quality for patients with acute ischemic stroke. CSCs exceeded PSCs in timely acute reperfusion therapy for emergency department admissions, whereas PSCs had lower risk-adjusted in-hospital mortality. This information may be important for acute stroke triage and targeted quality improvement. PMID- 29794033 TI - Prediction of response to drug therapy in psychiatric disorders. AB - Personalized medicine has become increasingly relevant to many medical fields, promising more efficient drug therapies and earlier intervention. The development of personalized medicine is coupled with the identification of biomarkers and classification algorithms that help predict the responses of different patients to different drugs. In the last 10 years, the Food and Drug Administration (FDA) has approved several genetically pre-screened drugs labelled as pharmacogenomics in the fields of oncology, pulmonary medicine, gastroenterology, haematology, neurology, rheumatology and even psychiatry. Clinicians have long cautioned that what may appear to be similar patient-reported symptoms may actually arise from different biological causes. With growing populations being diagnosed with different psychiatric conditions, it is critical for scientists and clinicians to develop precision medication tailored to individual conditions. Genome-wide association studies have highlighted the complicated nature of psychiatric disorders such as schizophrenia, bipolar disorder, major depression and autism spectrum disorder. Following these studies, association studies are needed to look for genomic markers of responsiveness to available drugs of individual patients within the population of a specific disorder. In addition to GWAS, the advent of new technologies such as brain imaging, cell reprogramming, sequencing and gene editing has given us the opportunity to look for more biomarkers that characterize a therapeutic response to a drug and to use all these biomarkers for determining treatment options. In this review, we discuss studies that were performed to find biomarkers of responsiveness to different available drugs for four brain disorders: bipolar disorder, schizophrenia, major depression and autism spectrum disorder. We provide recommendations for using an integrated method that will use available techniques for a better prediction of the most suitable drug. PMID- 29794036 TI - Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk. AB - The regional distribution of adipose tissues is implicated in a wide range of diseases. For example, proportional increases in visceral adipose tissue increase the risk for insulin resistance, diabetes, and CVD. Zebrafish offer a tractable model system by which to obtain unbiased and quantitative phenotypic information on regional adiposity, and deep phenotyping can explore complex disease-related adiposity traits. To facilitate deep phenotyping of zebrafish adiposity traits, we used pairwise correlations between 67 adiposity traits to generate stage specific adiposity profiles that describe changing adiposity patterns and relationships during growth. Linear discriminant analysis classified individual fish according to an adiposity profile with 87.5% accuracy. Deep phenotyping of eight previously uncharacterized zebrafish mutants identified neuropilin 2b as a novel gene that alters adipose distribution. When we applied deep phenotyping to identify changes in adiposity during diet manipulations, zebrafish that underwent food restriction and refeeding had widespread adiposity changes when compared with continuously fed, equivalently sized control animals. In particular, internal adipose tissues (e.g., visceral adipose) exhibited a reduced capacity to replenish lipid following food restriction. Together, these results in zebrafish establish a new deep phenotyping technique as an unbiased and quantitative method to help uncover new relationships between genotype, diet, and adiposity. PMID- 29794032 TI - Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease. AB - Abhydrolase domain containing 16A (ABHD16A) is a member of the alpha/beta hydrolase domain-containing (ABHD) protein family and is expressed in a variety of animal cells. Studies have shown that ABHD16A has acylglycerol lipase and phosphatidylserine lipase activities. Its gene location in the main histocompatibility complex (MHC) III gene cluster suggests that this protein may participate in the immunomodulation of the body. The results of studies investigating nearly 20 species of ABHDs reveal that the ABHD proteins are key factors in metabolic regulation and disease occurrence and development. In this paper, we summarize the related progress regarding the function of ABHD16A and other ABHD proteins. A prediction of the active sites and structural domains of ABHD16A and an analysis of the amino acid sites are included. Moreover, we analysed the amino acid sequences of the ABHD16A molecules in different species and provide an overview of the related functions and diseases associated with these proteins. The functions and diseases related to ABHD are systematically summarized and highlighted. Future research directions for studies investigating the functions and mechanisms of these proteins are also suggested. Further studies investigating the function of ABHD proteins may further confirm their positions as important determinants of lipid metabolism and related diseases. PMID- 29794037 TI - Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells. AB - Ceramides contribute to obesity-linked insulin resistance and inflammation in vivo, but whether this is a cell-autonomous phenomenon is debated, particularly in muscle, which dictates whole-body glucose uptake. We comprehensively analyzed lipid species produced in response to fatty acids and examined the consequence to insulin resistance and pro-inflammatory pathways. L6 myotubes were incubated with BSA-adsorbed palmitate or palmitoleate in the presence of myriocin, fenretinide, or fumonisin B1. Lipid species were determined by lipidomic analysis. Insulin sensitivity was scored by Akt phosphorylation and glucose transporter 4 (GLUT4) translocation, while pro-inflammatory indices were estimated by IkappaBalpha degradation and cytokine expression. Palmitate, but not palmitoleate, had mild effects on Akt phosphorylation but significantly inhibited insulin-stimulated GLUT4 translocation and increased expression of pro-inflammatory cytokines Il6 and Ccl2 Ceramides, hexosylceramides, and sphingosine-1-phosphate significantly heightened by palmitate correlated negatively with insulin sensitivity and positively with pro-inflammatory indices. Inhibition of sphingolipid pathways led to marked changes in cellular lipids, but did not prevent palmitate-induced impairment of insulin-stimulated GLUT4 translocation, suggesting that palmitate induced accumulation of deleterious lipids and insulin resistance are correlated but independent events in myotubes. We propose that muscle cell-endogenous ceramide production does not evoke insulin resistance and that deleterious effects of ceramides in vivo may arise through ancillary cell communication. PMID- 29794038 TI - Perceived Social Isolation and Outcomes in Patients With Heart Failure. AB - BACKGROUND: Perceived social isolation has been shown to have a negative impact on health outcomes, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure. METHODS AND RESULTS: Residents from 11 southeast Minnesota counties with a first-ever International Classification of Diseases, Ninth Revision (ICD-9) code 428 for heart failure between January 1, 2013, and March 31, 2015 (N=3867), were prospectively surveyed to measure perceived social isolation. A total of 2003 patients returned the survey (response rate, 52%); 1681 patients completed all questions and were retained for analysis. Among these patients (53% men; mean age, 73 years), ~19% (n=312) had moderate perceived social isolation and 6% (n=108) had high perceived social isolation. After adjustment, patients reporting moderate perceived social isolation did not have an increased risk of death, hospitalizations, or emergency department visits compared with patients reporting low perceived social isolation; however, patients reporting high perceived social isolation had >3.5 times increased risk of death (hazard ratio, 3.74; 95% confidence interval [CI], 1.82-7.70), 68% increased risk of hospitalization (hazard ratio, 1.68; 95% CI, 1.18-2.39), and 57% increased risk of emergency department visits (hazard ratio, 1.57; 95% CI, 1.09-2.27). Compared with patients who self-reported low perceived social isolation, patients reporting moderate perceived social isolation had a 16% increased risk of outpatient visits (rate ratio, 1.16; 95% CI, 1.03-1.31), whereas those reporting high perceived social isolation had a 26% increased risk (rate ratio, 1.26; 95% CI, 1.04-1.53). CONCLUSIONS: In patients with heart failure, greater perceived social isolation is associated with an increased risk of death and healthcare use. Assessing perceived social isolation during the clinical encounter with a brief screening tool may help identify patients with heart failure at greater risk of poor outcomes. PMID- 29794039 TI - Exaggerated groups: amplification in ensemble coding of temporal and spatial features. AB - The human visual system represents summary statistical information (e.g. average) along many visual dimensions efficiently. While studies have indicated that approximately the square root of the number of items in a set are effectively integrated through this ensemble coding, how those samples are determined is still unknown. Here, we report that salient items are preferentially weighted over the other less salient items, by demonstrating that the perceived means of spatial (i.e. size) and temporal (i.e. flickering temporal frequency (TF)) features of the group of items are positively biased as the number of items in the group increases. This illusory 'amplification effect' was not the product of decision bias but of perceptual bias. Moreover, our visual search experiments with similar stimuli suggested that this amplification effect was due to attraction of visual attention to the salient items (i.e. large or high TF items). These results support the idea that summary statistical information is extracted from sets with an implicit preferential weighting towards salient items. Our study suggests that this saliency-based weighting may reflect a more optimal and efficient integration strategy for the extraction of spatio-temporal statistical information from the environment, and may thus be a basic principle of ensemble coding. PMID- 29794040 TI - Collective ritual and social support networks in rural South India. AB - The scholarship on religion has long argued that collective worship helps foster social cohesion. Despite the pervasiveness of this contention, rigorous quantitative evaluations of it have been surprisingly limited. Here, I draw on network data representing the ties of social support among Hindu residents of a South Indian village to evaluate the association between collective religious ritual and social cohesion. I find that those who partake in collective religious rituals together have a higher probability of having a supportive relationship than those who do not. At the structural level, this corresponds to denser connections among co-participants. At the individual level, participants are more embedded in the local community of co-religionists, but are not disassociating themselves from members of other religious denominations. These patterns hold most strongly for co-participation in the recurrent, low-arousal monthly worships at the temple, and are suggestive for co-participation in the intense and dysphoric ritual acts carried out as part of an annual festival. Together, these findings provide clear empirical evidence of the lasting relationship between collective religious ritual and social cohesion. PMID- 29794042 TI - Mechanisms and seasonal drivers of calcification in the temperate coral Turbinaria reniformis at its latitudinal limits. AB - High-latitude coral reefs provide natural laboratories for investigating the mechanisms and limits of coral calcification. While the calcification processes of tropical corals have been studied intensively, little is known about how their temperate counterparts grow under much lower temperature and light conditions. Here, we report the results of a long-term (2-year) study of seasonal changes in calcification rates, photo-physiology and calcifying fluid (cf) chemistry (using boron isotope systematics and Raman spectroscopy) for the coral Turbinaria reniformis growing near its latitudinal limits (34.5 degrees S) along the southern coast of Western Australia. In contrast with tropical corals, calcification rates were found to be threefold higher during winter (16 to 17 degrees C) compared with summer (approx. 21 degrees C), and negatively correlated with light, but lacking any correlation with temperature. These unexpected findings are attributed to a combination of higher chlorophyll a, and hence increased heterotrophy during winter compared with summer, together with the corals' ability to seasonally modulate pHcf, with carbonate ion concentration [Formula: see text] being the main controller of calcification rates. Conversely, calcium ion concentration [Ca2+]cf declined with increasing calcification rates, resulting in aragonite saturation states Omegacf that were stable yet elevated fourfold above seawater values. Our results show that corals growing near their latitudinal limits exert strong physiological control over their cf in order to maintain year-round calcification rates that are insensitive to the unfavourable temperature regimes typical of high-latitude reefs. PMID- 29794043 TI - Sex-specific effects of inbreeding on reproductive senescence. AB - Inbreeding depression plays a significant role in evolutionary biology and ecology. However, we lack a clear understanding of the fitness consequences of inbreeding depression. Studies often focus on short-term effects of inbreeding in juvenile offspring, whereas inbreeding depression in adult traits and the interplay between inbreeding depression and age are rarely addressed. Inbreeding depression may increase with age and accelerate the decline in reproductive output in ageing individuals (reproductive senescence), which could be subject to sex-specific dynamics. We test this hypothesis with a longitudinal experimental study in a short-lived songbird. Adult inbred and outbred male and female canaries were paired in a 2 * 2 factorial design, and survival and annual reproductive performance were studied for 3 years. We found inbreeding depression in female egg-laying ability, male fertilization success and survival of both sexes. Annual reproductive success of both males and females declined when paired with an inbred partner independent of their own inbreeding status. This shows that inbreeding can have fitness costs in outbred individuals when they mate with an inbred individual. Further, inbred females showed faster reproductive senescence than outbred females, confirming that inbreeding depression and age can interact to affect fitness. By contrast, there was no evidence for an interaction between inbreeding depression and reproductive senescence in male fertilization success. Our findings highlight the importance of considering sex specific effects and age to determine the full range of fitness consequences of inbreeding and demonstrate that inbreeding depression can accelerate reproductive senescence. PMID- 29794044 TI - Inter-generational change in African elephant range use is associated with poaching risk, primary productivity and adult mortality. AB - Repeated use of the same areas may benefit animals as they exploit familiar sites, leading to consistent home ranges over time that can span generations. Changing risk landscapes may reduce benefits associated with home range fidelity, however, and philopatric animals may alter movement in response to new pressures. Despite the importance of range changes to ecological and evolutionary processes, little tracking data have been collected over the long-term nor has range change been recorded in response to human pressures across generations. Here, we investigate the relationships between ecological, demographic and human variables and elephant ranging behaviour across generations using 16 years of tracking data from nine distinct female social groups in a population of elephants in northern Kenya that was heavily affected by ivory poaching during the latter half of the study. Nearly all groups-including those that did not experience loss of mature adults-exhibited a shift north over time, apparently in response to increased poaching in the southern extent of the study area. However, loss of mature adults appeared to be the primary indicator of range shifts and expansions, as generational turnover was a significant predictor of range size increases and range centroid shifts. Range expansions and northward shifts were associated with higher primary productivity and lower poached carcass densities, while westward shifts exhibited a trend to areas with higher values of primary productivity and higher poached carcass densities relative to former ranges. Together these results suggest a trade-off between resource access, mobility and safety. We discuss the relevance of these results to elephant conservation efforts and directions meriting further exploration in this disrupted society of a keystone species. PMID- 29794041 TI - Mitochondrial genetic effects on reproductive success: signatures of positive intrasexual, but negative intersexual pleiotropy. AB - Theory predicts that maternal inheritance of mitochondria will facilitate the accumulation of mtDNA mutations that are male biased, or even sexually antagonistic, in effect. While there are many reported cases of mtDNA mutations conferring cytoplasmic male sterility in plants, historically it was assumed such mutations would not persist in the streamlined mitochondrial genomes of bilaterian metazoans. Intriguingly, recent cases of mitochondrial variants exerting male biases in effect have come to light in bilaterians. These cases aside, it remains unknown whether the mitochondrial genetic variation affecting phenotypic expression, and in particular reproductive performance, in bilaterians is routinely composed of sex-biased or sex-specific variation. If selection consistently favours mtDNA variants that augment female fitness, but at cost to males, this could shape patterns of pleiotropy and lead to negative intersexual correlations across mtDNA haplotypes. Here, we show that genetic variation across naturally occurring mitochondrial haplotypes affects components of reproductive success in both sexes, in the fruit fly Drosophila melanogaster We find that intrasexual correlations across mitochondrial haplotypes, for components of reproductive success, are generally positive, while intersexual correlations are negative. These results accord with theoretical predictions, suggesting that maternal inheritance has led to the fixation of numerous mutations of sexually antagonistic effect. PMID- 29794045 TI - Migration promotes plasmid stability under spatially heterogeneous positive selection. AB - Bacteria-plasmid associations can be mutualistic or antagonistic depending on the strength of positive selection for plasmid-encoded genes, with contrasting outcomes for plasmid stability. In mutualistic environments, plasmids are swept to high frequency by positive selection, increasing the likelihood of compensatory evolution to ameliorate the plasmid cost, which promotes long-term stability. In antagonistic environments, plasmids are purged by negative selection, reducing the probability of compensatory evolution and driving their extinction. Here we show, using experimental evolution of Pseudomonas fluorescens and the mercury-resistance plasmid, pQBR103, that migration promotes plasmid stability in spatially heterogeneous selection environments. Specifically, migration from mutualistic environments, by increasing both the frequency of the plasmid and the supply of compensatory mutations, stabilized plasmids in antagonistic environments where, without migration, they approached extinction. These data suggest that spatially heterogeneous positive selection, which is common in natural environments, coupled with migration helps to explain the stability of plasmids and the ecologically important genes that they encode. PMID- 29794046 TI - Morph-specific artificial selection reveals a constraint on the evolution of polyphenisms. AB - Theory predicts that the evolution of polyphenic variation is facilitated where morphs are genetically uncoupled and free to evolve towards their phenotypic optima. However, the assumption that developmentally plastic morphs can evolve independently has not been tested directly. Using morph-specific artificial selection, we investigated correlated evolution between the sexes and male morphs of the bulb mite Rhizoglyphus echinopus Large 'fighter' males have a thick and sharply terminating pair of legs used to kill rival males, while small 'scrambler' males have unmodified legs, and search for unguarded females, avoiding fights. We selected on the relative leg width of only the fighter male morph, tracked the evolutionary responses in fighters and the correlated evolutionary responses in scramblers and females that were untouched by direct selection. Fighters diverged in relative leg thickness after six generations; assaying scramblers and females at the ninth generation we observed correlated responses in relative leg width in both. Our results represent strong evidence for the evolution of intraspecific phenotypic diversity despite correlated evolution between morphs and sexes, challenging the idea that male morphs are genetically uncoupled and free to independently respond to selection. We therefore question the perceived necessity for genetic independence in traits with extreme phenotypic plasticity. PMID- 29794048 TI - Behavioural homogenization with spillovers in a normative domain. AB - The importance of culture for human social evolution hinges largely on the extent to which culture supports outcomes that would not otherwise occur. An especially controversial claim is that social learning leads groups to coalesce around group typical behaviours and associated social norms that spill over to shape choices in asocial settings. To test this, we conducted an experiment with 878 groups of participants in 116 communities in Sudan. Participants watched a short film and evaluated the appropriate way to behave in the situation dramatized in the film. Each session consisted of an asocial condition in which participants provided private evaluations and a social condition in which they provided public evaluations. Public evaluations allowed for social learning. Across sessions, we randomized the order of the two conditions. Public choices dramatically increased the homogeneity of normative evaluations. When the social condition was first, this homogenizing effect spilled over to subsequent asocial conditions. The asocial condition when first was thus alone in producing distinctly heterogeneous groups. Altogether, information about the choices of others led participants to converge rapidly on similar normative evaluations that continued to hold sway in subsequent asocial settings. These spillovers were at least partly owing to the combined effects of conformity and self-consistency. Conformity dominated self consistency when the two mechanisms were in conflict, but self-consistency otherwise produced choices that persisted through time. Additionally, the tendency to conform was heterogeneous. Females conformed more than males, and conformity increased with the number of other people a decision-maker observed before making her own choice. PMID- 29794047 TI - Peripherally injected ghrelin and leptin reduce food hoarding and mass gain in the coal tit (Periparus ater). AB - In birds little is known about the hormonal signals that communicate nutritional state to the brain and regulate appetitive behaviours. In mammals, the peptide hormones ghrelin and leptin elevate and inhibit consumption and food hoarding, respectively. But in birds, administration of both ghrelin and leptin inhibit food consumption. The role of these hormones in the regulation of food hoarding in avian species has not been examined. To investigate this, we injected wild caught coal tits (Periparus ater) with leptin, high-dose ghrelin, low-dose ghrelin and a saline control in the laboratory. We then measured food hoarding and mass gain, as a proxy of food consumption, every 20 min for 2 h post injection. Both high-dose ghrelin and leptin injections significantly reduced hoarding and mass gain compared with controls. Our results provide the first evidence that hoarding behaviour can be reduced by both leptin and ghrelin in a wild bird. These findings add to evidence that the hormonal control of food consumption and hoarding in avian species differs from that in mammals. Food hoarding and consumptive behaviours consistently show the same response to peripheral signals of nutritional state, suggesting that the hormonal regulation of food hoarding has evolved from the consumption regulatory system. PMID- 29794050 TI - Phytoplankton size diversity and ecosystem function relationships across oceanic regions. AB - Trait diversity, a key component of biodiversity, mediates many essential ecosystem functions and services. However, the mechanisms behind such relationships at large spatial scales are not fully understood. Here we adopt the functional biogeography approach to investigate how the size composition of phytoplankton communities relates to primary production and export production along a broad latitudinal gradient. Using in situ phytoplankton size distribution data and a trait-based model, we find an increase in the average phytoplankton size, size diversity, primary production and export when moving from low to high latitudes. Our analysis indicates that the interplay between spatio-temporal heterogeneities in environmental conditions and a trade-off between the high affinity for nutrients of smaller cells and the ability to avoid predation by larger cells are the main mechanisms driving the observed patterns. Our results also suggest that variations in size diversity alone do not directly lead to changes in primary production and export. The trade-off thus introduces a feedback that influences the relationship between size diversity and ecosystem functions. These findings support the importance of environmentally mediated trade-offs as crucial mechanisms shaping biodiversity and ecosystem function relationships at large spatial scales. PMID- 29794049 TI - Magnetocarcinogenesis: is there a mechanism for carcinogenic effects of weak magnetic fields? AB - Extremely low-frequency (ELF) magnetic fields have been classified as possibly carcinogenic, mainly based on rather consistent epidemiological findings suggesting a link between childhood leukaemia and 50-60 Hz magnetic fields from power lines. However, causality is not the only possible explanation for the epidemiological associations, as animal and in vitro experiments have provided only limited support for carcinogenic effects of ELF magnetic fields. Importantly, there is no generally accepted biophysical mechanism that could explain such effects. In this review, we discuss the possibility that carcinogenic effects are based on the radical pair mechanism (RPM), which seems to be involved in magnetoreception in birds and certain other animals, allowing navigation in the geomagnetic field. We review the current understanding of the RPM in magnetoreception, and discuss cryptochromes as the putative magnetosensitive molecules and their possible links to cancer-relevant biological processes. We then propose a hypothesis for explaining the link between ELF fields and childhood leukaemia, discuss the strengths and weaknesses of the current evidence, and make proposals for further research. PMID- 29794051 TI - Evidence for atypical nest overwintering by hatchling lizards, Heloderma suspectum. AB - The timing of reproductive events (e.g. oviposition and hatching) to coincide with favourable seasonal conditions is critical for successful reproduction. However, developmental time may not match the duration between the optimal time for oviposition and the optimal time for hatchling survival. Thus, strategies that alter the time between oviposition and hatchling emergence can be highly advantageous. Arrested development and the resulting extension of the duration between oviposition and hatching has been widely documented across oviparous amniotes, but nest overwintering by hatchlings has only been documented in aquatic chelonians that live where winters are quite cold. Herein, we present a compilation of evidence regarding reproductive phenology by hatchlings of the Gila monster (Heloderma suspectum), a lizard inhabiting the Sonoran Desert of North America. Our data demonstrate that (i) Gila monster hatchlings from eggs oviposited in July do not emerge from their nests until late spring or summer of the following year, yet (ii) Gila monster eggs artificially incubated at field relevant temperatures hatch in 4-5 months. Furthermore, we describe a fortuitous excavation of a hatching Gila monster nest in late October, which coincides with the artificial incubation results. Together, these results provide strong support for the existence of overwintering in the nest by a lizard, and suggest that this reproductive strategy should be explored in a broader array of taxa. PMID- 29794052 TI - Density-dependent interspecific interactions and the complexity-stability relationship. AB - Ever since May theorized that communities with larger numbers of species or interspecific interactions are inherently unstable, the mechanism allowing for the stable existence of complex communities in nature has been a central question in ecology. The main efforts to answer this question have sought to identify non random features of ecological systems that can reverse a negative complexity stability relationship into a positive one, but are far from successful, especially in their generality. Here, using the traditional community matrix analysis, we show that variation in the density dependence of interspecific interactions, which should be ubiquitous in nature, can dramatically affect the complexity-stability relationship. More specifically, we reveal that a positive complexity-stability relationship arises when harmful interspecific effects have larger density dependence than beneficial ones, regardless of the signs (i.e. positive or negative) of their dependence. Furthermore, numerical simulations demonstrated the synergistic stabilizing effect of interaction type diversity and density-dependence variation. Thus, this concept of density-dependence variation advances our understanding of the complexity-stability relationship in the real world. PMID- 29794053 TI - ROM mapping of ligamentous constraints on avian hip mobility: implications for extinct ornithodirans. AB - Studies of soft tissue effects on joint mobility in extant animals can help to constrain hypotheses about joint mobility in extinct animals. However, joint mobility must be considered in three dimensions simultaneously, and applications of mobility data to extinct taxa require both a phylogenetically informed reconstruction of articular morphology and justifications for why specific structures' effects on mobility are inferred to be similar. We manipulated cadaveric hip joints of common quail and recorded biplanar fluoroscopic videos to measure a 'ligamentous' range of motion (ROM), which was then compared to an 'osteological' ROM on a ROM map. Nearly 95% of the joint poses predicted to be possible at the hip based on osteological manipulation were rendered impossible by ligamentous constraints. Because the hip joint capsule reliably includes a ventral ligamentous thickening in extant diapsids, the hip abduction of extinct ornithodirans with an offset femoral head and thin articular cartilage was probably similarly constrained by ligaments as that of birds. Consequently, in the absence of extraordinary evidence to the contrary, our analysis casts doubt on the 'batlike' hip pose traditionally inferred for pterosaurs and basal maniraptorans, and underscores that reconstructions of joint mobility based on manipulations of bones alone can be misleading. PMID- 29794055 TI - Genetic Variation of the SusC/SusD Homologs from a Polysaccharide Utilization Locus Underlies Divergent Fructan Specificities and Functional Adaptation in Bacteroides thetaiotaomicron Strains. AB - Genomic differences between gut-resident bacterial strains likely underlie significant interindividual variation in microbiome function. Traditional methods of determining community composition, such as 16S rRNA gene amplicon sequencing, fail to capture this functional diversity. Metagenomic approaches are a significant step forward in identifying strain-level sequence variants; however, given the current paucity of biochemical information, they too are limited to mainly low-resolution and incomplete functional predictions. Using genomic, biochemical, and molecular approaches, we identified differences in the fructan utilization profiles of two closely related Bacteroides thetaiotaomicron strains. B. thetaiotaomicron 8736 (Bt-8736) contains a fructan polysaccharide utilization locus (PUL) with a divergent susC/susD homolog gene pair that enables it to utilize inulin, differentiating this strain from other characterized Bt strains. Transfer of the distinct pair of susC/susD genes from Bt-8736 into the noninulin using type strain B. thetaiotaomicronVPI-5482 resulted in inulin use by the recipient strain, Bt(8736-2). The presence of the divergent susC/susD gene pair alone enabled the hybrid Bt(8736-2) strain to outcompete the wild-type strain in vivo in mice fed an inulin diet. Further, we discovered that the susC/susD homolog gene pair facilitated import of inulin into the periplasm without surface predigestion by an endo-acting enzyme, possibly due to the short average chain length of inulin compared to many other polysaccharides. Our data builds upon recent reports of dietary polysaccharide utilization mechanisms found in members of the Bacteroides genus and demonstrates how the acquisition of two genes can alter the functionality and success of a strain within the gut.IMPORTANCE Dietary polysaccharides play a dominant role in shaping the composition and functionality of our gut microbiota. Dietary interventions using these microbiota-accessible carbohydrates (MACs) serve as a promising tool for manipulating the gut microbial community. However, our current gap in knowledge regarding microbial metabolic pathways that are involved in the degradation of these MACs has made the design of rational interventions difficult. The issue is further complicated by the diversity of pathways observed for the utilization of similar MACs, even in closely related microbial strains. Our current work focuses on divergent fructan utilization pathways in two closely related B. thetaiotaomicron strains and provides an integrated approach to characterize the molecular basis for strain level functional differences. PMID- 29794054 TI - An Observational Cohort Study of Clostridium difficile Ribotype 027 and Recurrent Infection. AB - Recurrent Clostridium difficile infection (rCDI) frequently complicates recovery from CDI. Accurately predicting rCDI would allow judicious allocation of limited resources, but published models have met with limited success. Thus, biomarkers predictive of recurrence have been sought. This study tested whether PCR ribotype independently predicted rCDI. Stool samples from nonpregnant inpatients >=18 years of age with diarrhea were included from October 2010 to January 2013 after the patients tested positive for C. difficile in the clinical microbiology laboratory. Per guidelines, the rCDI was defined as a positive test for C. difficile at >2 weeks but <=8 weeks from the index episode. For each sample, a single colony of C. difficile was isolated by anaerobic culture, confirmed to be toxigenic by PCR, and ribotyped. Simple logistic regression and multiple logistic regression were used to model the primary outcome of rCDI, incorporating a wide range of clinical parameters. In total, 927 patients with 968 index episodes of CDI were included, with 110 (11.4%) developing rCDI. Age and use of proton pump inhibitors or concurrent antibiotics did not increase the risk of rCDI. Low serum bilirubin levels and ribotype 027 were associated with increased risk of rCDI on unadjusted analysis, with health care-associated CDI being inversely associated. In the final multivariable model, ribotype 027 was the strongest independent predictor of rCDI (odds ratio, 2.17; 95% confidence interval, 1.33 to 3.56; P = 0.002). Ribotype 027 is an independent predictor of rCDI.IMPORTANCE CDI is a major public health issue, with over 400,000 cases per year in the United States alone. Recurrent CDI is common, occurring in approximately one in five individuals after a primary episode. Although interventions exist that could reduce the risk of recurrence, deployment in all patients is limited by cost, invasiveness, and/or an undetermined long-term safety profile. Thus, clinicians need risk stratification tools to properly allocate treatments. Because prior research on clinical predictors has failed to yield a reliable, reproducible, and effective predictive model to assist treatment decisions, accurate biomarkers of recurrence would be of great value. This study tested whether PCR ribotype independently predicted rCDI, and the data build upon prior research in showing that ribotype 027 is associated with rCDI. PMID- 29794056 TI - Peptide-Like Nylon-3 Polymers with Activity against Phylogenetically Diverse, Intrinsically Drug-Resistant Pathogenic Fungi. AB - Understanding the dimensions of fungal diversity has major implications for the control of diseases in humans, plants, and animals and in the overall health of ecosystems on the planet. One ancient evolutionary strategy organisms use to manage interactions with microbes, including fungi, is to produce host defense peptides (HDPs). HDPs and their synthetic analogs have been subjects of interest as potential therapeutic agents. Due to increases in fungal disease worldwide, there is great interest in developing novel antifungal agents. Here we describe activity of polymeric HDP analogs against fungi from 18 pathogenic genera composed of 41 species and 72 isolates. The synthetic polymers are members of the nylon-3 family (poly-beta-amino acid materials). Three different nylon-3 polymers show high efficacy against surprisingly diverse fungi. Across the phylogenetic spectrum (with the exception of Aspergillus species), yeasts, dermatophytes, dimorphic fungi, and molds were all sensitive to the effects of these polymers. Even fungi intrinsically resistant to current antifungal drugs, such as the causative agents of mucormycosis (Rhizopus spp.) and those with acquired resistance to azole drugs, showed nylon-3 polymer sensitivity. In addition, the emerging pathogens Pseudogymnoascus destructans (cause of white nose syndrome in bats) and Candida auris (cause of nosocomial infections of humans) were also sensitive. The three nylon-3 polymers exhibited relatively low toxicity toward mammalian cells. These findings raise the possibility that nylon-3 polymers could be useful against fungi for which there are only limited and/or no antifungal agents available at present.IMPORTANCE Fungi reside in all ecosystems on earth and impart both positive and negative effects on human, plant, and animal health. Fungal disease is on the rise worldwide, and there is a critical need for more effective and less toxic antifungal agents. Nylon-3 polymers are short, sequence random, poly-beta-amino acid materials that can be designed to manifest antimicrobial properties. Here, we describe three nylon-3 polymers with potent activity against the most phylogenetically diverse set of fungi evaluated thus far in a single study. In contrast to traditional peptides, nylon-3 polymers are highly stable to proteolytic degradation and can be produced efficiently in large quantities at low cost. The ability to modify nylon-3 polymer composition easily creates an opportunity to tailor efficacy and toxicity, which makes these materials attractive as potential broad-spectrum antifungal therapeutics. PMID- 29794058 TI - Cancer metabolism gets physical. AB - Patient-derived culture models enable assessment of drug sensitivity and can connect personalized genomics with therapeutic options. However, their clinical translation is constrained by limited fidelity. We outline how the physical microenvironment regulates cell metabolism and describe how engineered culture systems could enhance the predictive power for precision medicine. PMID- 29794059 TI - Adult rat myelin enhances axonal outgrowth from neural stem cells. AB - Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell-derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal-regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI. PMID- 29794057 TI - Genes Activated by Vibrio cholerae upon Exposure to Caenorhabditis elegans Reveal the Mannose-Sensitive Hemagglutinin To Be Essential for Colonization. AB - During its life cycle, the facultative human pathogen Vibrio cholerae, which is the causative agent of the diarrheal disease cholera, needs to adapt to a variety of different conditions, such as the human host or the aquatic environment. Importantly, cholera infections originate from the aquatic reservoir where V. cholerae persists between the outbreaks. In the aquatic environment, bacteria are constantly threatened by predatory protozoa and nematodes, but our knowledge of the response pathways and adaptation strategies of V. cholerae to such stressors is limited. Using a temporally controlled reporter system of transcription, we identified more than 100 genes of V. cholerae induced upon exposure to the nematode Caenorhabditis elegans, which emerged recently as a valuable model for environmental predation during the aquatic lifestyle of V. cholerae Besides others, we identified and validated the genes encoding the mannose-sensitive hemagglutinin (MSHA) type IV pilus to be significantly induced upon exposure to the nematode. Subsequent analyses demonstrated that the mannose-sensitive hemagglutinin is crucial for attachment of V. cholerae in the pharynx of the worm and initiation of colonization, which results in growth retardation and developmental delay of C. elegans Thus, the surface adhesion factor MSHA could be linked to a fitness advantage of V. cholerae upon contact with bacterium-grazing nematodes.IMPORTANCE The waterborne diarrheal disease cholera is caused by the bacterium Vibrio cholerae The facultative human pathogen persists as a natural inhabitant in the aquatic ecosystem between outbreaks. In contrast to the human host, V. cholerae requires a different set of genes to survive in this hostile environment. For example, predatory micrograzers are commonly found in the aquatic environment and use bacteria as a nutrient source, but knowledge of the interaction between bacterivorous grazers and V. cholerae is limited. In this study, we successfully adapted a genetic reporter technology and identified more than 100 genes activated by V. cholerae upon exposure to the bacterium-grazing nematode Caenorhabditis elegans This screen provides a first glimpse into responses and adaptational strategies of the bacterial pathogen against such natural predators. Subsequent phenotypic characterization revealed the mannose sensitive hemagglutinin to be crucial for colonization of the worm, which causes developmental delay and growth retardation. PMID- 29794060 TI - Striatal dopamine regulates systemic glucose metabolism in humans and mice. AB - The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D1 receptor-expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism. PMID- 29794061 TI - A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent. AB - Vascular normalizing strategies, aimed at ameliorating blood vessel perfusion and lessening tissue hypoxia, are treatments that may improve the outcome of cancer patients. Secreted class 3 semaphorins (SEMA3), which are thought to directly bind neuropilin (NRP) co-receptors that, in turn, associate with and elicit plexin (PLXN) receptor signaling, are effective normalizing agents of the cancer vasculature. Yet, SEMA3A was also reported to trigger adverse side effects via NRP1. We rationally designed and generated a safe, parenterally deliverable, and NRP1-independent SEMA3A point mutant isoform that, unlike its wild-type counterpart, binds PLXNA4 with nanomolar affinity and has much greater biochemical and biological activities in cultured endothelial cells. In vivo, when parenterally administered in mouse models of pancreatic cancer, the NRP1 independent SEMA3A point mutant successfully normalized the vasculature, inhibited tumor growth, curbed metastatic dissemination, and effectively improved the supply and anticancer activity of chemotherapy. Mutant SEMA3A also inhibited retinal neovascularization in a mouse model of age-related macular degeneration. In summary, mutant SEMA3A is a vascular normalizing agent that can be exploited to treat cancer and, potentially, other diseases characterized by pathological angiogenesis. PMID- 29794062 TI - Derepression of co-silenced tumor suppressor genes by nanoparticle-loaded circular ssDNA reduces tumor malignancy. AB - The co-silencing of multiple tumor suppressor genes can lead to escalated malignancy in cancer cells. Given the limited efficacy of anticancer therapies targeting single tumor suppressor genes, we developed small circular single stranded DNA (CSSD) that can up-regulate the expression of co-silenced tumor suppressor genes by sequestering microRNAs (miRNAs) that negatively regulate these genes. We found that cancer patients with low tumor expression of the tumor suppressor genes KLF17, CDH1, and LASS2 had shortened survival times. The up regulation of these genes upon transfection of artificial CSSD-9 inhibited tumor proliferation and metastasis and promoted apoptosis in vitro as well as in ex vivo and patient-derived xenograft models. In addition, CSSD is more stable and effective than current miRNA inhibitors, and transfecting CSSDs via nanoparticles substantially improved delivery efficiency. The use of a single CSSD can promote the inhibition of multiple tumor suppressor genes. This study provides evidence for the possibility of using CSSDs as therapeutic miRNA inhibitors to target the co-silencing of multiple tumor suppressor genes. PMID- 29794064 TI - Allocating healthcare resources-seriously ill people should have priority. PMID- 29794063 TI - The Defense Phytohormone Signaling Network Enables Rapid, High-Amplitude Transcriptional Reprogramming during Effector-Triggered Immunity. AB - The phytohormone network consisting of jasmonate, ethylene, PHYTOALEXIN DEFICIENT4, and salicylic acid signaling is required for the two modes of plant immunity, pattern-triggered immunity (PTI), and effector-triggered immunity (ETI). A previous study showed that during PTI, the transcriptional responses of over 5000 genes qualitatively depend on complex interactions between the network components. However, the role of the network in transcriptional reprogramming during ETI and whether it differs between PTI and ETI remain elusive. Here, we generated time-series RNA-sequencing data of Arabidopsis thaliana wild-type and combinatorial mutant plants deficient in components of the network upon challenge with virulent or ETI-triggering avirulent strains of the foliar bacterial pathogen Pseudomonas syringae Resistant plants such as the wild type achieved high-amplitude transcriptional reprogramming 4 h after challenge with avirulent strains and sustained this transcriptome response. Strikingly, susceptible plants including the quadruple network mutant showed almost identical transcriptome responses to resistant plants but with several hours delay. Furthermore, gene coexpression network structure was highly conserved between the wild type and quadruple mutant. Thus, in contrast to PTI, the phytohormone network is required only for achieving high-amplitude transcriptional reprogramming within the early time window of ETI against this bacterial pathogen. PMID- 29794065 TI - Malignant peritoneal mesothelioma in patients with endometriosis. AB - AIMS: Florid mesothelial hyperplasia is known to result from endometriosis. Well differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis. METHODS: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis. RESULTS: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01). CONCLUSIONS: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum. PMID- 29794067 TI - Shared Decision Making Emphasized for Prostate Screening. AB - The U.S. Preventive Services Task Force (USPSTF) now recommends that men ages 55 to 69 individually decide, in consultation with their physician, whether to undergo PSA screening for prostate cancer. The guidelines represent a change from 2012, when the USPSTF recommended against screening for all men. PMID- 29794066 TI - Phase II Study of Everolimus and Octreotide LAR in Patients with Nonfunctioning Gastrointestinal Neuroendocrine Tumors: The GETNE1003_EVERLAR study. AB - BACKGROUND: Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. MATERIALS AND METHODS: This prospective, multicenter, single arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (GI-NETs) that progressed in the last 12 months (ClinicalTrials.gov NCT01567488). Prior treatment with SSAs and any systemic or locoregional therapy was allowed except for mTOR inhibitors. Patients continued treatment until disease progression or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) at 12 months; secondary endpoints included early biochemical response, objective response rate (ORR) by RECIST v1.0, overall survival (OS), AEs, activation of mTOR pathway (insulin-like growth factor 1 receptor [IGF1R] and phosphoS6 [pS6] expression). RESULTS: Forty three patients were included in the intent-to-treat analyses. After 12 months of treatment, 62.3% (95% confidence interval [CI] 48%-77%) of patients had not progressed or died. The 24-month PFS rate was 43.6% (95% CI 29%-58%). The confirmed ORR was 2.3%, and stable disease was 58.1%. Median OS was not reached after 24 months of median follow-up. Dose reductions and temporary interruptions due to AEs were required in 14 (33%) and 33 (77%) patients, respectively. The most frequent AEs were diarrhea, asthenia, mucositis, rash, and hyperglycemia. No correlation was observed between IGFR1 and pS6 expression and PFS/OS. CONCLUSION: The everolimus-octreotide combination provided clinically relevant efficacy in nonfunctioning GI-NETs, similar to the results of RADIANT-2 in functioning setting. IMPLICATIONS FOR PRACTICE: The EVERLAR study reports prospective data of somatostatin analogue in combination with everolimus in nonfunctioning gastrointestinal neuroendocrine tumors suggesting meaningful activity and favorable toxicity profile that supports drug combination in this setting. PMID- 29794068 TI - GPIbalpha is required for platelet-mediated hepatic thrombopoietin generation. AB - Thrombopoietin (TPO), a hematopoietic growth factor produced predominantly by the liver, is essential for thrombopoiesis. Prevailing theory posits that circulating TPO levels are maintained through its clearance by platelets and megakaryocytes via surface c-Mpl receptor internalization. Interestingly, we found a two- to threefold decrease in circulating TPO in GPIbalpha-/- mice compared with wild type (WT) controls, which was consistent in GPIbalpha-deficient human Bernard Soulier syndrome (BSS) patients. We showed that lower TPO levels in GPIbalpha deficient conditions were not due to increased TPO clearance by GPIbalpha-/- platelets but rather to decreased hepatic TPO mRNA transcription and production. We found that WT, but not GPIbalpha-/-, platelet transfusions rescued hepatic TPO mRNA and circulating TPO levels in GPIbalpha-/- mice. In vitro hepatocyte cocultures with platelets or GPIbalpha-coupled beads further confirm the disruption of platelet-mediated hepatic TPO generation in the absence of GPIbalpha. Treatment of GPIbalpha-/- platelets with neuraminidase caused significant desialylation; however, strikingly, desialylated GPIbalpha-/- platelets could not rescue impaired hepatic TPO production in vivo or in vitro, suggesting that GPIbalpha, independent of platelet desialylation, is a prerequisite for hepatic TPO generation. Additionally, impaired hepatic TPO production was recapitulated in interleukin-4/GPIbalpha-transgenic mice, as well as with antibodies targeting the extracellular portion of GPIbalpha, demonstrating that the N terminus of GPIbalpha is required for platelet-mediated hepatic TPO generation. These findings reveal a novel nonredundant regulatory role for platelets in hepatic TPO homeostasis, which improves our understanding of constitutive TPO regulation and has important implications in diseases related to GPIbalpha, such as BSS and auto- and alloimmune-mediated thrombocytopenias. PMID- 29794070 TI - Government's response to L239m worth of inquiries has been "opaque," says NAO. PMID- 29794069 TI - Call for independent monitoring of disease outbreak preparedness. PMID- 29794071 TI - Access to patient records while on telephone consultations. PMID- 29794072 TI - Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis. AB - OBJECTIVES: To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. DESIGN: Cross sectional analysis. SETTING: Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. MAIN OUTCOME MEASURES: Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. RESULTS: Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. CONCLUSIONS: Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. PMID- 29794073 TI - Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? AB - We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant. Patient age correlated with donor-recipient relationship: haploidentical siblings donated to patients aged 18 to 54 years whereas offspring donated to patients aged 55 to 76 years. Therefore, transplant outcomes were examined separately in the 2 patient age groups. In patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant (hazard ratio [HR], 0.63; P < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; P < .001), graft failure (14% vs 6%; P = .003), nonrelapse mortality (HR, 1.48; P = .02), and overall mortality (HR, 1.32; P = .003) were higher after transplant from offspring compared with an HLA matched sibling. These data demonstrate a superior outcome in older recipients when using an HLA-matched sibling instead of offspring, although there were differences in transplant platforms (GVHD prophylaxis and graft type) between the 2 groups. Validation of these findings requires a prospective randomized trial wherein the transplant platforms can be closely matched. PMID- 29794075 TI - MRD in HCL: does it matter? PMID- 29794077 TI - Five years of ibrutinib in CLL. PMID- 29794074 TI - Tau Mutations Serve as a Novel Risk Factor for Cancer. AB - In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. In addition, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathologic roles of mutated tau.Significance: This study reveals a novel role for tau as a risk factor for cancer, providing new insights beyond its role in neurodegeneration. Cancer Res; 78(13); 3731-9. (c)2018 AACR. PMID- 29794078 TI - Leukemic-phase progression of aleukemic mast cell leukemia. PMID- 29794076 TI - The future of kinase inhibitors for DLBCL? PMID- 29794079 TI - Taxes must rise to fund 5% budget increase the NHS needs. PMID- 29794080 TI - Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. AB - South Asians (from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka) make up one quarter of the world's population and are one of the fastest-growing ethnic groups in the United States. Although native South Asians share genetic and cultural risk factors with South Asians abroad, South Asians in the United States can differ in socioeconomic status, education, healthcare behaviors, attitudes, and health insurance, which can affect their risk and the treatment and outcomes of atherosclerotic cardiovascular disease (ASCVD). South Asians have higher proportional mortality rates from ASCVD compared with other Asian groups and non-Hispanic whites, in contrast to the finding that Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) aggregated as a group are at lower risk of ASCVD, largely because of the lower risk observed in East Asian populations. Literature relevant to South Asian populations regarding demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies, is summarized. The evidence to date is that the biology of ASCVD is complex but is no different in South Asians than in any other racial/ethnic group. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially those related to insulin resistance, and no unique risk factors in this population have been found. This scientific statement focuses on how ASCVD risk factors affect the South Asian population in order to make recommendations for clinical strategies to reduce disease and for directions for future research to reduce ASCVD in this population. PMID- 29794081 TI - Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation. AB - BACKGROUND: Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation. METHODS: We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random effects model. The I2 test was used to assess heterogeneity in RR among the studies. RESULTS: In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I2=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I2=26.3%). CONCLUSIONS: The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin. PMID- 29794083 TI - Adenosine and Ticagrelor Plasma Levels in Patients With and Without Ticagrelor Related Dyspnea. PMID- 29794082 TI - Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages. AB - BACKGROUND: We previously showed that mice lacking MPhiLRP1-/- (low-density lipoprotein receptor-related protein 1 in macrophages) undergo accelerated atherosclerotic plaque formation due to changes in macrophages including increased apoptosis, decreased efferocytosis, and exaggerated transition to the inflammatory M1 phenotype. Here we sought to explore the role of macrophage low density lipoprotein receptor-related protein 1 during regression of atherosclerosis since regressing plaques are characterized by transitioning of macrophages to M2 status as inflammation resolves. METHODS: Apolipoprotein E-/- mice on a high-fat diet for 12 weeks were reconstituted with bone marrow from apolipoprotein E-producing wild-type or MPhiLRP1-/- mice, and then placed on a chow diet for 10 weeks (n=9 to 11 mice/group). A cohort of apolipoprotein E-/- mice reconstituted with apolipoprotein E-/- bone marrow served as baseline controls (n=9). RESULTS: Plaques of both wild-type and MPhiLRP1-/- bone marrow recipients regressed compared with controls (11% and 22%, respectively; P<0.05), and plaques of MPhiLRP1-/- recipients were 13% smaller than those of wild-type recipients ( P<0.05). Recipients of MPhiLRP1-/- marrow had 36% fewer M1 macrophages ( P<0.01) and 2.5-fold more CCR7 (C-C chemokine receptor type 7) positive macrophages in the plaque relative to wild-type mice ( P<0.01). Additionally, in vivo studies of cellular egress showed a 4.6-fold increase in 5 ethynyl-2'-deoxyuridine-labeled CCR7+ macrophages in mediastinal lymph nodes. Finally, in vivo studies of reverse cholesterol transport showed a 1.4-fold higher reverse cholesterol transport in MPhiLRP1-/- recipient mice ( P<0.01). CONCLUSIONS: Absence of macrophage low-density lipoprotein receptor-related protein 1 unexpectedly accelerates atherosclerosis regression, enhances reverse cholesterol transport, and increases expression of the motility receptor CCR7, which drives macrophage egress from lesions. PMID- 29794085 TI - Do all daily metabolic equivalent task units (METs) bring the same health benefits? PMID- 29794084 TI - An unusual rash on the feet. PMID- 29794087 TI - Winter pressure: England's health regulator publishes tips to help emergency departments cope better next year. PMID- 29794086 TI - Cardiovascular screening of Olympic athletes reported by chief medical officers of the Rio 2016 Olympic Games. AB - OBJECTIVE: The IOC recommends periodic cardiovascular screening of athletes, but the adoption of these recommendations is unknown. The purpose of this investigation was to evaluate and compare cardiovascular screening practices of countries participating in the Rio 2016 Olympic Games. METHODS: A list of chief medical officers (CMOs) was compiled by the IOC during the 2016 Olympic Games. CMOs were requested to complete an online survey about cardiovascular screening of their countries' Olympic athletes. Comparisons of screening practices were made by categorising countries by continent, gross domestic product (GDP) per capita and size of athlete delegation. RESULTS: CMOs for 117/207 (56.5%) countries participating in the 2016 Olympic Games were identified. 94/117 countries (80.3%) completed the survey, representing 45.4% of all countries and 8805/11 358 (77.5%) of all 2016 Olympic athletes. Most of the countries surveyed (70.2%) perform annual cardiovascular screening. Among the survey respondents, all or most athletes from each country were screened at least once with the following components: personal history (86.2% of countries), family history (85.1%), physical examination (87.2%), resting ECG (74.5%), echocardiogram (31.9%) and stress test (30.8%). Athletes were more likely to be screened with ECG in countries with relatively larger athlete delegation (OR 2.05, 95% CI 1.10 to 3.80, p=0.023) and with higher GDP per capita (OR 1.69, 95% CI 1.11 to 2.57, p=0.014). CONCLUSION: Most of the responding countries perform annual cardiovascular screening of Olympic athletes, but there are differences in the components used. Athletes from countries with larger athlete delegations and higher GDP per capita were more likely to be screened with ECG. PMID- 29794088 TI - Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios. AB - OBJECTIVES: To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. DESIGN: A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. SETTING: Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. PARTICIPANTS: Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. MAIN OUTCOME MEASURES: The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost effectiveness analysis. RESULTS: Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of L20 000-L30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately L40). CONCLUSION: Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway. PMID- 29794089 TI - China Intracranial Aneurysm Project (CIAP): protocol for a prospective cohort study of interventional treatment and craniotomy for unruptured aneurysms. AB - INTRODUCTION: There are two approaches for the treatment of intracranial aneurysm (IA): interventional therapy and craniotomy, both of which have their advantages and disadvantages in terms of treatment efficacy. To avoid overtreatment of unruptured aneurysms (UIA), to save valuable medical resources and to reduce patient mortality and disability rate, it is vital that neurosurgeons select the most appropriate type of treatment to provide the best levels of care. In this study, we propose a refined, prospective, multicentre study for the Chinese population with strictly defined patient inclusion criteria, along with the selection of representative clinical participating centres. METHODS AND ANALYSIS: This report describes a multicentre, prospective cohort study. As IA is extremely harmful if it ruptures, ethical issues need to be taken into account with regard to this study. Researchers are therefore not able to use randomised controlled trials. The study will be conducted by 12 clinical centres located in different regions of China. The trial recruitment programme begins in 2016 and is scheduled to be completed in 2020. We expect 1500 participants with UIA to be included. Clinical information relating to the participants will be recorded objectively. The primary endpoints are an evaluation of the safety and efficiency of interventional treatment and craniotomy for 6 months after surgery, with each participant completing at least 1 year of follow-up. The secondary endpoint is the evaluation of safety and efficacy of interventional therapy and craniotomy clipping when participants are treated for 12 months. We also address the success of treatment and the incidence of adverse events. ETHICS AND DISSEMINATION: The research protocol and the informed consent form for participants in this study were approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2017-SJWK-001). The results of this study are expected to be disseminated in peer-reviewed journals in 2021. TRIAL REGISTRATION NUMBER: NCT03133598. PMID- 29794090 TI - Second-generation antipsychotic medications and risk of chronic kidney disease in schizophrenia: population-based nested case-control study. AB - OBJECTIVES: The study aims to compare the risk of chronic kidney diseases (CKDs) between patients with schizophrenia using first and second-generation antipsychotics. SETTING: Datasets of 2000-2013 National Health Insurance in Taiwan were used. PARTICIPANTS: The National Health Insurance reimbursement claims data have been transferred to and managed by the National Health Research Institute in Taiwan since 1996. We used the Psychiatric Inpatient Medical Claims database, a subset of the National Health Insurance Research Database, comprising a cohort of patients hospitalised for psychiatric disorders between 2000 and 2013 (n=2 67 807). The database included patients with at least one psychiatric inpatient record and one discharge diagnosis of mental disorders coded by the International Classification of Diseases, Ninth Revision (ICD-9) codes 290-319. The age of patients at first admission was restricted to 18-65 years. PRIMARY OUTCOME: CKD (ICD-9 code 582, 583, 585, 586, 588) requiring hospitalisation or three outpatient visits. The diagnosis of CKD follows the criteria of 'Kidney Disease: Improving Global Outcomes' in Taiwan. CKD is defined as a kidney damage as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens or glomerular filtration rate <60 mL/min/1.73 m2 for 3 months or more. RESULTS: We found that the risks for CKD were higher for those who used second-generation antipsychotics (SGAs) longer cumulatively than those who did not. Using non users, patients did not have any SGA records, as reference group, the risks for CKD comparing those using SGAs for 90 to 180 days with non-users and those using SGAs for more than 1000 days were 1.42 (1.06-1.91) and 1.30 (1.13-1.51), respectively. CONCLUSIONS: The current study suggests the relationship between using SGAs and risk of CKD. PMID- 29794091 TI - Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical centre. AB - OBJECTIVES: To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs). DESIGN: A retrospective cohort study. SETTING: A tertiary university hospital in South Korea. PARTICIPANTS: 410 patients with 410 incidentally detected SSNs who underwent surgical resection for the pulmonary adenocarcinoma spectrum between 2011 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Using clinical and radiological variables, the predicted probability of MIA/IPA was calculated from pre-existing logistic models (Brock and Lee models). Areas under the receiver operating characteristic curve (AUCs) were calculated and compared between models. Performance metrics including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were also obtained. RESULTS: For pure ground-glass nodules (n=101), the AUC of the Brock model in differentiating MIA/IPA (59/101) from preinvasive lesions (42/101) was 0.671. Sensitivity, specificity, accuracy, PPV and NPV based on the optimal cut-off value were 64.4%, 64.3%, 64.4%, 71.7% and 56.3%, respectively. Sensitivity, specificity, accuracy, PPV and NPV according to the Lee criteria were 76.3%, 42.9%, 62.4%, 65.2% and 56.3%, respectively. AUC was not obtained for the Lee model as a single cut-off of nodule size (>=10 mm) was suggested by this model for the assessment of pure ground-glass nodules. For part solid nodules (n=309; 26 preinvasive lesions and 283 MIA/IPAs), the AUC was 0.746 for the Brock model and 0.771 for the Lee model (p=0.574). Sensitivity, specificity, accuracy, PPV and NPV were 82.3%, 53.8%, 79.9%, 95.1% and 21.9%, respectively, for the Brock model and 77.0%, 69.2%, 76.4%, 96.5% and 21.7%, respectively, for the Lee model. CONCLUSIONS: The performance of prediction models for the incidentally detected SSNs in differentiating MIA/IPA from preinvasive lesions might be suboptimal. Thus, an alternative risk calculation model is required for the incidentally detected SSNs. PMID- 29794092 TI - Gelatine tannate in the management of acute gastroenteritis in children: a randomised controlled trial. AB - OBJECTIVE: To assess the efficacy of gelatine tannate (a complex of tannic acid with astringent and anti-inflammatory properties, and a protective gelatine) for the treatment of acute gastroenteritis (AGE) in children. DESIGN: Randomised, double-blind, placebo-controlled trial. Intention-to-treat analysis. SETTING: Two paediatric hospitals in Warsaw. PARTICIPANTS: Children younger than 5 years of age with AGE, defined as a change in stool consistency to a loose or liquid form (according to the Bristol Stool Form Scale or Amsterdam Stool Form Scale) and/or an increase in the frequency of evacuations (>=3 in 24 hours), lasting for no longer than 5 days. INTERVENTIONS: Seventy-two children were assigned to receive gelatine tannate (n=36) or placebo (n=36) in addition to standard rehydration therapy. The gelatine tannate was administered at an age-dependent dose (250-500 mg), and both study products were taken four times per day for 5 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome measure was duration of diarrhoea. Secondary outcomes included the need for intravenous rehydration, need for hospitalisation of outpatients, number of watery stools per day, vomiting, weight gain, adverse events, recurrence of diarrhoea, severity of diarrhoea according to the Vesikari Scale and use of concomitant medications. RESULTS: Sixty-four children (89%) completed the intervention and were included in the analysis. The duration of diarrhoea after randomisation was similar in the gelatine tannate and placebo groups (75.6+/-27.8 vs 75.5+/-29.0 hours, respectively, mean difference 0.1 hours, 95% CI -14.1 to 14.3 hours). There was no significant difference between groups in the number of watery stools per day throughout the study period. There were also no differences in any other secondary outcome measures between groups. CONCLUSION: In children with AGE younger than 5 years of age, gelatine tannate was ineffective as an adjunct to rehydration therapy. TRIAL REGISTRATION NUMBER: NCT02280759. PMID- 29794093 TI - Exploring emergency department 4-hour target performance and cancelled elective operations: a regression analysis of routinely collected and openly reported NHS trust data. AB - OBJECTIVE: To quantify the effect of intrahospital patient flow on emergency department (ED) performance targets and indicate if the expectations set by the National Health Service (NHS) England 5-year forward review are realistic in returning emergency services to previous performance levels. DESIGN: Linear regression analysis of routinely reported trust activity and performance data using a series of cross-sectional studies. SETTING: NHS trusts in England submitting routine nationally reported measures to NHS England. PARTICIPANTS: 142 acute non-specialist trusts operating in England between 2012 and 2016. MAIN OUTCOME MEASURES: The primary outcome measures were proportion of 4-hour waiting time breaches and cancelled elective operations. METHODS: Univariate and multivariate linear regression models were used to show relationships between the outcome measures and various measures of trust activity including empty day beds, empty night beds, day bed to night bed ratio, ED conversion ratio and delayed transfers of care. RESULTS: Univariate regression results using the outcome of 4 hour breaches showed clear relationships with empty night beds and ED conversion ratio between 2012 and 2016. The day bed to night bed ratio showed an increasing ability to explain variation in performance between 2015 and 2016. Delayed transfers of care showed little evidence of an association. Multivariate model results indicated that the ability of patient flow variables to explain 4-hour target performance had reduced between 2012 and 2016 (19% to 12%), and had increased in explaining cancelled elective operations (7% to 17%). CONCLUSIONS: The flow of patients through trusts is shown to influence ED performance; however, performance has become less explainable by intratrust patient flow between 2012 and 2016. Some commonly stated explanatory factors such as delayed transfers of care showed limited evidence of being related. The results indicate some of the measures proposed by NHS England to reduce pressure on EDs may not have the desired impact on returning services to previous performance levels. PMID- 29794094 TI - Prevalence of peritonitis and mortality in patients treated with continuous ambulatory peritoneal dialysis (CAPD) in Africa: a protocol for a systematic review and meta-analysis. AB - INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD) is the ideal modality for renal replacement therapy in most African settings given that it is relatively cheaper than haemodialysis (HD) and does not require in-centre care. CAPD is, however, not readily utilised as it is often complicated by peritonitis leading to high rates of technique failure. The objective of this study is to assess the prevalence of CAPD-related peritonitis and all-cause mortality in patients treated with CAPD in Africa. METHODS AND ANALYSIS: We will search PubMed, EMBASE, SCOPUS, Africa Journal Online and Google Scholar for studies conducted in Africa from 1 January 1980 to 30 June 2017 with no language restrictions. Eligible studies will include cross-sectional, prospective observational and cohort studies of patients treated with CAPD. Two authors will independently screen, select studies, extract data and conduct risk of bias assessment. Data consistently reported across studies will be pooled using random effects meta-analysis. Heterogeneity will be evaluated using Cochrane's Q statistic and quantified using I2 statistics. Graphical and formal statistical tests will be used to assess for publication bias. ETHICS AND DISSEMINATION: Ethical approval will not be needed for this study as data used will be extracted from already published studies. Results of this review will be published in a peer-reviewed journal and presented at conferences. The Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015) framework guided the development of this protocol. PROSPERO REGISTRATION NUMBER: CRD42017072966. PMID- 29794095 TI - Non-pharmacological interventions for the prevention of hypertension in low income and middle-income countries: protocol for a systematic review and meta analysis. AB - INTRODUCTION: In recent times, hypertension has become one of the major public health concerns in both the developed and the developing world and is responsible for death due to heart diseases and stroke. The increasing trend of the prevalence of hypertension in low-income and middle-income countries (LMICs) and it's catastrophic consequences have made the phenomenon important to continue to investigate interventions for its prevention and control. Different dietary and lifestyle-related approaches have been recommended for the prevention of hypertension. The aim of this proposed review is to explore the available non pharmacological interventions tried for the prevention of hypertension in LMICs. METHODS AND ANALYSIS: Eight electronic databases will be searched covering the period between 1990 and 2016 to identify relevant studies and will be screened by two independent reviewers. The searched articles will be included for full-text extraction applying definitive inclusion and exclusion criteria. Appropriate critical appraisal tools including the Cochrane Handbook for Systematic Reviews of Interventions will be used to assess the risk of bias. Disagreement between the two reviewers will be resolved by a third reviewer. Narrative synthesis of the findings will be provided along with summaries of the intervention effect. A meta-analysis will be undertaken using the random-effects model where applicable. Heterogeneity between the studies will be assessed, and sensitivity analysis will be conducted based on study quality. ETHICS AND DISSEMINATION: Approval from the institutional review board has been taken for this review. Findings will be summarised in a single manuscript.This review is an attempt to explore the available non-pharmacological approaches for the prevention of hypertension in LMICs. Findings from the review will highlight effective non-pharmacological measures for the prevention of hypertension to guide policy for future strategies. PROSPERO REGISTRATION NUMBER: CRD42017055423. PMID- 29794096 TI - Is disability exclusion associated with psychological distress? Australian evidence from a national cross-sectional survey. AB - OBJECTIVE: To examine the association between disability exclusion and psychological distress. DESIGN: Cross-sectional study. SETTING: Population-based study of individuals living in households across Australia. PARTICIPANTS: Respondents were persons aged 15 and over living with a disability. PRIMARY OUTCOME MEASURES: Reporting an experience of discrimination or avoidance behaviour due to a respondent's disability. High or very high levels of psychological distress measured using the Kessler K10 instrument. METHODOLOGY: Using the Survey of Disability, Ageing and Carers, we calculated the prevalence of persons with a disability experiencing psychological distress, disaggregated by experiences of disability exclusion, including discrimination and avoidance. Logistic regression models were fitted to examine the association between disability exclusion and psychological distress, once extensive controls and adjustments for survey design and presence of psychosocial disabilities were considered. RESULTS: About 62% of persons citing an experience of disability discrimination were in psychological distress, compared with 27% of those citing no discrimination. Furthermore, 53% of those who actively avoided social, familial or economic activities because of their disability experienced psychological distress, compared with 19% of those who did not avoid these situations. After controlling for demographic characteristics and disabling conditions, reporting an experience of disability discrimination or disability avoidance increased the odds of psychological distress by 2.2 (95% CI 1.74 to 2.26) and 2.6 (95% CI 2.28 to 2.97) times, respectively. Those who experienced both avoidance and discrimination were 3.7 (95% CI 2.95 to 4.72) times more likely to be in psychological distress than those experiencing neither. Avoidance and discrimination in healthcare settings were also found to be strongly associated with experiencing psychological distress. CONCLUSIONS: Given new policy initiatives to improve disability care, coupled with the increasing speed of population ageing, the onus is on governments and its citizenry to address disability exclusion to offset potential mental health impacts. PMID- 29794098 TI - Financial, opportunity and psychosocial costs of spinal muscular atrophy: an exploratory qualitative analysis of Australian carer perspectives. AB - OBJECTIVES: Spinal muscular atrophy (SMA) has profound implications for patients and families. The aim of the present study was to gain insights into the effects caring for a child with SMA has on the costs incurred by families caring for a child with SMA from carer perspectives to identify gaps in provision of care, inform public policy and cost-effectiveness analyses. DESIGN: Interpretive phenomenological analysis guided the delivery and analysis of semi-structured interviews undertaken to explore the financial, opportunity and psychosocial costs associated with caring for children with SMA. PARTICIPANTS AND SETTING: Parents of children with SMA types II and III from a single Australian paediatric neuromuscular clinic participated in this study. RESULTS: A range of experiences were reported and information saturation (n=7) was reached endorsing themes, including: significant financial and caregiving burdens, adjusted career choices and limitations on career progression and a complex landscape of access to funding, equipment, support and resources. Opportunity costs of foregone employment, purchases and leisure activities were substantial, as were emotional and social impacts. Participants voiced determination and resilience, and called for continued efforts to improve supportive care services and resources. CONCLUSIONS: The range and nature of costs met by families caring for a child with SMA were found to be expansive and not typically recognised. These include high direct costs associated with goods and services, indirect costs associated with voluntary care, substantial and long-term opportunities foregone in paid employment and career progression and unmeasured or hidden costs associated with mental health burden. PMID- 29794097 TI - Polypharmacy among patients with diabetes: a cross-sectional retrospective study in a tertiary hospital in Saudi Arabia. AB - : ObjectivesPatients with diabetes are at high risk for polypharmacy (ie, use of multiple medications) for treatment of diabetes, associated comorbidities and other coexisting conditions. This study aims to estimate the prevalence of polypharmacy and factors associated with polypharmacy among adult patients with diabetes. METHODS: A cross-sectional retrospective observational study of adults with diabetes, who visited the outpatient clinic of a tertiary teaching hospital in Saudi Arabia, was conducted. Data were extracted from the Electronic Health Record database for a period of 12 months (January-December 2016). Polypharmacy was defined as the cumulative use of five or more medications. Polypharmacy among adults with diabetes was measured by calculating the average number of medications prescribed per patient. A multivariable logistic regression model was used to examine the factors associated with polypharmacy. RESULTS: A total of 8932 adults with diabetes were included in this study. Of these, nearly 78% had polypharmacy which was more likely among women as compared with men and more likely among older adults (age >=60 years) as compared with the adults. Also, polypharmacy was two times as likely among patients with coexisting cardiovascular conditions (adjusted OR (AOR)=2.89; 95% CI 2.54 to 3.29), respiratory disease (AOR=2.42; 95% CI 1.92 to 3.03) and mental health conditions (AOR=2.19; 95% CI 1.74 to 2.76), and three times as likely among patients with coexisting musculoskeletal disease (AOR=3.16; 95% CI 2.31 to 4.30) as compared with those without these coexisting chronic conditions categories. CONCLUSIONS: Polypharmacy is common among patients with diabetes, with an even higher rate in older adults patients. Healthcare providers can help in detecting polypharmacy and in providing recommendations for simplifying medication regimens and minimising medications to enhance the outcome of diabetes care. PMID- 29794099 TI - Partly randomised, controlled study in children aged 6-10 years to investigate motor and cognitive effects of a 9-week coordination training intervention with concurrent mental tasks. AB - INTRODUCTION: Physical training may play a prominent role in the development of preadolescent brains, but it is yet to be determined what type of exercise may generate higher cognitive effects, and if concurrent mental engagement provides further efficacy. The aim of this study is to investigate motor and cognitive effects of a 9-week exercise intervention in children aged 6-10 years. Trainings include the automatisation of challenging coordination exercises with concurrent mental tasks (intervention group) and multisport exercises with and without mental tasks (two control groups). It is hypothesised that all groups gain motor and cognitive effects, but highest benefits are expected for the combination of automatised coordination exercises with mental tasks. METHODS AND ANALYSIS: Two elementary schools (~500 students) take part in the study. Data are generated by using the German Motor Performance Test 6-18 (Deutscher Motorik-Test 6-18), TDS (Match 4 Point), d2-R test of attention and Kasel-Concentration-Task for Children Aged 3-8 Years; test-duration: 6-7 min. After pretesting in September 2017 and a 9-week training intervention, post-testing takes place in December 2017 and March 2018 (long-term effects). Training interventions consist of coordination exercises with concurrent mental tasks (intervention group) and multimotor exercises with and without concurrent mental tasks (control groups). Shapiro-Wilk test will be used to test for normal distribution and the Levene test for variance homogeneity. The appropriate multivariate statistical methods (multivariate analysis of variance or Kruskal-Wallis test) will be used for analysing differences among the groups and for comparing preintervention with postintervention performances. ETHICS AND DISSEMINATION: All procedures have been approved by the board for ethical questions in science of the University of Innsbruck. Findings will be published in 2018 in international journals and presented at conferences. Schools will be informed of key results. PMID- 29794100 TI - Linkage to care among adults being investigated for tuberculosis in South Africa: pilot study of a case manager intervention. AB - OBJECTIVES: We piloted an intervention to determine if support from a case manager would assist adults being investigated for tuberculosis (TB) to link into TB and HIV care. DESIGN: Pilot interventional cohort study. PARTICIPANTS AND SETTING: Patients identified by primary healthcare clinic staff in South Africa as needing TB investigations were enrolled. INTERVENTION: Participants were supported for 3 months by case managers who facilitated the care pathway by promoting HIV testing, getting laboratory results, calling patients to return for results and facilitating treatment initiation. OUTCOMES MEASURED: Linkage to TB care was defined as starting TB treatment within 28 days in those with a positive test result; linkage to HIV care, for HIV-positive people, was defined as having blood taken for CD4 count and, for those eligible, starting antiretroviral therapy within 3 months. Intervention implementation was measured by number of attempts to contact participants. RESULTS: Among 562 participants (307 (54.6%) female, median age: 36 years (IQR 29-44)), most 477 (84.8%) had previously tested for HIV; of these, 328/475 (69.1%) self-reported being HIV-positive. Overall, 189/562 (33.6%) participants needed linkage to care (132 HIV care linkage only; 35 TB treatment linkage only; 22 both). Of 555 attempts to contact these 189 participants, 407 were to facilitate HIV care linkage, 78 for TB treatment linkage and 70 for both. At the end of 3-month follow-up, 40 participants had not linked to care (29 of the 132 (22.0%) participants needing linkage to HIV care only, 4 of the 35 (11.4%) needing to start on TB treatment only and 7 of the 22 (31.8%) needing both). CONCLUSION: Many people testing for TB need linkage to care. Despite case manager support, non-linkage into HIV care remained higher than desirable, suggesting a need to modify this intervention before implementation. Innovative strategies to enable linkage to care are needed. PMID- 29794101 TI - Reperfusion Injury after ischemic Stroke Study (RISKS): single-centre (Florence, Italy), prospective observational protocol study. AB - INTRODUCTION: Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood-brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury. METHODS AND ANALYSIS: Observational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered at http://www.clinicaltrials.gov (ClinicalTrials.gov ID: NCT03041753). ETHICS AND DISSEMINATION: The study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Universita degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis. TRIAL REGISTRATION NUMBER: NCT03041753. PMID- 29794102 TI - Cardiac complications after stroke: protocol for a systematic review and meta analysis. AB - INTRODUCTION: Stroke is the second most common cause of death after ischaemic heart diseases and the third leading cause of disability worldwide. The contribution of cardiac complications to the mortality of patients with stroke is variable across studies, ranging from 12.5% to 22.7%. Many of these cardiac complications are preventable, and early recognition and adequate management guided by appropriate up-to-date knowledge of their relative incidence and fatality can help to improve patients' outcomes. This systematic review aims to summarise the available data on the burden of cardiac complications after stroke. METHODS AND ANALYSIS: This review will include all cross-sectional, case-control and cohort studies and clinical trials published between 1 January 1950 and 31 December 2017, involving adults and/or children, and reporting on the prevalence, the incidence and/or the mortality of cardiac complications after stroke. Two reviewers will independently screen titles and abstracts of records retrieved from PubMed, Excerpta Medica Database, ISI Web of Science and the Cumulative Index to Nursing and Allied Health Literature for eligibility, and then assess the risk of bias and quality of reporting to select the studies which will be included. All authors will contribute to the retrieval of full texts of eligible records and data extraction. Heterogeneity across studies will be evaluated by the chi2 test on Cochran's Q statistic. Study-specific estimates of the prevalence, incidence and mortality of cardiac complications after stroke across studies will be pooled through random-effect or fixed-effect meta-analysis depending on the source of the heterogeneity, after stabilising the variance of individual studies using the Freeman-Tukey double arcsine transformation. Visual analysis of funnel plots and Egger's test will be done to detect small-study effect. ETHICS AND DISSEMINATION: This review and meta-analysis will be based on published data and will therefore not require a specific ethical clearance. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42018082551. PMID- 29794104 TI - Alcohol-related presentations to emergency departments in Ireland: a descriptive prevalence study. AB - OBJECTIVES: To determine the prevalence of alcohol-related presentations in all 29 emergency departments (EDs) in Ireland and compare with non-alcohol-related presentations in order to identify opportunities for improvements in the quality of patient care and related data collection. DESIGN AND SETTING: Descriptive prevalence study reviewing all records in the same four 6-hour periods in every 24-hour ED in the country. PARTICIPANTS: 3194 persons who attended EDs over four specified 6-hour periods. PRIMARY OUTCOME MEASURES: The prevalence of alcohol related presentations, comparison with non-alcohol-related presentations and the categorisation of these presentations according to WHO International Statistical Classification of Diseases and Related Health Problems 10th Revision codes. RESULTS: The total number of presentations was 3194 in the four 6-hour periods, of whom 189 (5.9%) were alcohol related, varying from 29.0% in the early hours of Sunday morning to 1.2% on Monday morning (p>0.0001). The alcohol-related presentations were more likely to be men, attend on early hours of Sunday morning, arrive by ambulance, leave before being seen by a doctor or leave against medical advice; and they were less likely to be admitted to hospital. CONCLUSIONS: Alcohol-related presentations are a significant burden on EDs and ambulance services, especially in the early hours of Sunday mornings. Addressing the alcohol-related burden on EDs requires improvements in data collection and information systems, the development of appropriate interventions and related referral services and better preventive actions for alcohol-related harm. PMID- 29794103 TI - Epidemiology of multimorbidity in New Zealand: a cross-sectional study using national-level hospital and pharmaceutical data. AB - OBJECTIVES: To describe the prevalence of multimorbidity (presence of two or more long-term health conditions) in the New Zealand (NZ) population, and compare risk of health outcomes by multimorbidity status. DESIGN: Cross-sectional analysis for prevalence of multimorbidity, with 1-year prospective follow-up for health outcomes. SETTING: NZ general population using national-level routine health data on hospital discharges and pharmaceutical dispensing. PARTICIPANTS: All NZ adults (aged 18+, n=3 489 747) with an active National Health Index number at the index date (1 January 2014). OUTCOME MEASURES: Prevalence of multimorbidity was calculated using two data sources: prior routine hospital discharge data (61 ICD 10 coded diagnoses from the M3 multimorbidity index); and recent pharmaceutical dispensing records (30 conditions from the P3 multimorbidity index). METHODS: Prevalence of multimorbidity was calculated separately for the two data sources, stratified by age group, sex, ethnicity and socioeconomic deprivation, and age and sex standardised to the total population. One-year risk of poor health outcomes (mortality, ambulatory sensitive hospitalisation (ASH) and overnight hospital admission) was compared by multimorbidity status using logistic regression adjusted for confounders. RESULTS: Prevalence of multimorbidity was 7.9% using past hospital discharge data, and 27.9% using past pharmaceutical dispensing data. Prevalence increased with age, with a clear socioeconomic gradient and differences in prevalence by ethnicity. Age and sex standardised risk of 1-year mortality was 2.7% for those with multimorbidity (defined on hospital discharge data), and 0.5% for those without multimorbidity (age and sex adjusted OR 4.8, 95% CI 4.7 to 5.0). Risk of ASH was also increased for those with multimorbidity (eg, pharmaceutical discharge definition: age and sex standardised risk 6.2%, compared with 1.8% for those without multimorbidity; age and sex-adjusted OR 3.6, 95% CI 3.5 to 3.6). CONCLUSIONS: Multimorbidity is common in the NZ adult population, with disparities in who is affected. Providing for the needs of individuals with multimorbidity requires collaborative and coordinated work across the health sector. PMID- 29794105 TI - Multimorbidity in children and youth: a scoping review protocol. AB - INTRODUCTION: Multimorbidity (co-occurring physical and mental illness) is an important issue for clinicians and researchers with combined efforts aimed at promoting the health and well-being of individuals across the life course. In children and youth, experience of any chronic physical illness leads to a substantial increase in risk for mental illness. As a growing field of interest, research is needed to map the current state of the literature in child and youth multimorbidity in order to identify existing gaps and inform the direction of future investigations. METHODS AND ANALYSIS: We are proposing the conduct of a scoping review to explore the depth and breadth of existing evidence in the field of child and youth multimorbidity. The scoping review will follow the methodological framework developed by Arksey and O'Malley, and will incorporate additional scoping review recommendations made by Levac et al. A systematic search of the following four key databases will be conducted: (1) PubMed; (2) EMBASE; (3) PsycINFO; and (4) Scopus, using combinations of Medical Subject Headings (MeSH) and Emtree terms. We will also consult grey literature sources and hand-search reference lists of included studies to identify additional studies of relevance. For eligible studies that meet all identified inclusion and exclusion criteria, a data extraction tool will be used to collect and store key study characteristics that will be relevant for collating, summarising and reporting the results of the scoping review. This scoping review also presents a novel use of quality index scoring, which we anticipate will contribute to strengthening the rigour of the scoping review methodology. ETHICS AND DISSEMINATION: The proposed scoping review does not require ethical approval. Final study results will be disseminated via conference presentations, publication in a peer-reviewed journal and knowledge translation activities with relevant stakeholders. PMID- 29794106 TI - Clinical prediction models for young febrile infants at the emergency department: an international validation study. AB - OBJECTIVE: To assess the diagnostic value of existing clinical prediction models (CPM; ie, statistically derived) in febrile young infants at risk for serious bacterial infections. METHODS: A systematic literature review identified eight CPMs for predicting serious bacterial infections in febrile children. We validated these CPMs on four validation cohorts of febrile children in Spain (age <3 months), France (age <3 months) and two cohorts in the Netherlands (age 1-3 months and >3-12 months). We evaluated the performance of the CPMs by sensitivity/specificity, area under the receiver operating characteristic curve (AUC) and calibration studies. RESULTS: The original cohorts in which the prediction rules were developed (derivation cohorts) ranged from 381 to 15 781 children, with a prevalence of serious bacterial infections varying from 0.8% to 27% and spanned an age range of 0-16 years. All CPMs originally performed moderately to very well (AUC 0.60-0.93). The four validation cohorts included 159 2204 febrile children, with a median age range of 1.8 (1.2-2.4) months for the three cohorts <3 months and 8.4 (6.0-9.6) months for the cohort >3-12 months of age. The prevalence of serious bacterial infections varied between 15.1% and 17.2% in the three cohorts <3 months and was 9.8% for the cohort >3-12 months of age. Although discriminative values varied greatly, best performance was observed for four CPMs including clinical signs and symptoms, urine dipstick analyses and laboratory markers with AUC ranging from 0.68 to 0.94 in the three cohorts <3 months (ranges sensitivity: 0.48-0.94 and specificity: 0.71-0.97). For the >3-12 months' cohort AUC ranges from 0.80 to 0.89 (ranges sensitivity: 0.70-0.82 and specificity: 0.78-0.90). In general, the specificities exceeded sensitivities in our cohorts, in contrast to derivation cohorts with high sensitivities, although this effect was stronger in infants <3 months than in infants >3-12 months. CONCLUSION: We identified four CPMs, including clinical signs and symptoms, urine dipstick analysis and laboratory markers, which can aid clinicians in identifying serious bacterial infections. We suggest clinicians should use CPMs as an adjunctive clinical tool when assessing the risk of serious bacterial infections in febrile young infants. PMID- 29794107 TI - Exploring how non-inferiority and equivalence are assessed in paediatrics: a systematic review. AB - OBJECTIVE: To review characteristics, methodology and reporting of non inferiority and equivalence trials in the specific context of paediatrics. DESIGN: PubMed and Cochrane databases were searched (up to September 2016) for non-inferiority/equivalence randomised controlled trials conducted in children published in high-impact-factor journals (>5.0 for general/specialist medical journals; >2.2 for paediatric journals). RESULTS: We found that the statistical hypothesis was inconsistent with the objective in 12 (10%) of the 125 reports included. Non-inferiority (n=98) and equivalence trials (n=27) were mostly used to evaluate interventions with easier administration (45%, n=54/120) and/or better safety profile (34%, n=41/120). All the data needed for targeted sample size recalculation were available for 39 reports (31%). The margin-representing the largest difference between arms that would be clinically acceptable-was reported in 119 (95%), and 44/119 (37%) reported the method used for margin determination. The median sample size was 268 (IQR 125-531). Margins were wider in smaller trials (<125 randomised patients) than in larger trials (p=0.04/p<0.01 for binary/continuous outcomes, respectively). We did not agree with the authors' conclusions in 11% (11/103) of the reports that provided sufficient information. CONCLUSIONS: There is still a need to improve the quality of methodology, reporting and interpretation of non-inferiority/equivalence trials in paediatrics. In particular, the margins were often not justified and the conclusion was often not supported by the design and/or the results. As researchers have to cope with small sample size and with lack of evidence, methods for non-inferiority/equivalence trials need to be used and/or developed in this vulnerable population. PMID- 29794108 TI - Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study. AB - BACKGROUND: Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity. METHODS: A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without. RESULTS: 12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03). CONCLUSIONS: These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF. PMID- 29794109 TI - Genetic Screening Test to Detect Translocations in Acute Leukemias by Use of Targeted Locus Amplification. AB - BACKGROUND: Over 500 translocations have been identified in acute leukemia. To detect them, most diagnostic laboratories use karyotyping, fluorescent in situ hybridization, and reverse transcription PCR. Targeted locus amplification (TLA), a technique using next-generation sequencing, now allows detection of the translocation partner of a specific gene, regardless of its chromosomal origin. We present a TLA multiplex assay as a potential first-tier screening test for detecting translocations in leukemia diagnostics. METHODS: The panel includes 17 genes involved in many translocations present in acute leukemias. Procedures were optimized by using a training set of cell line dilutions and 17 leukemia patient bone marrow samples and validated by using a test set of cell line dilutions and a further 19 patient bone marrow samples. Per gene, we determined if its region was involved in a translocation and, if so, the translocation partner. To balance sensitivity and specificity, we introduced a gray zone showing indeterminate translocation calls needing confirmation. We benchmarked our method against results from the 3 standard diagnostic tests. RESULTS: In patient samples passing QC, we achieved a concordance with benchmarking tests of 81% in the training set and 100% in the test set, after confirmation of 4 and nullification of 3 gray zone calls (in total). In cell line dilutions, we detected translocations in 10% aberrant cells at several genetic loci. CONCLUSIONS: Multiplex TLA shows promising results as an acute leukemia screening test. It can detect cryptic and other translocations in selected genes. Further optimization may make this assay suitable for diagnostic use. PMID- 29794111 TI - Algorithmically outsourcing the detection of statistical errors and other problems. PMID- 29794110 TI - 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma. AB - Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm. PMID- 29794112 TI - How DNA vicinity controls SUMO E3 ligase activity. PMID- 29794113 TI - Blood pressure-lowering treatment lowers mortality and cardiovascular disease risk, but whether effects differ at an arbitrary threshold of 140 mm Hg systolic blood pressure requires further research. PMID- 29794114 TI - JCAD, a Gene at the 10p11 Coronary Artery Disease Locus, Regulates Hippo Signaling in Endothelial Cells. AB - Objective- A large number of genetic loci have been associated with risk of coronary artery disease (CAD) through genome-wide association studies, however, for most loci the underlying biological mechanism is unknown. Determining the molecular pathways and cellular processes affected by these loci will provide new insights into CAD pathophysiology and may lead to new therapies. The CAD associated variants at 10p11.23 fall in JCAD, which encodes an endothelial junction protein, however, its molecular function in endothelial cells is not known. In this study, we characterize the molecular role of JCAD (junctional cadherin 5 associated) in endothelial cells. Approach and Results- We show that JCAD knockdown in endothelial cells affects key phenotypes related to atherosclerosis including proliferation, migration, apoptosis, tube formation, and monocyte binding. We demonstrate that JCAD interacts with LATS2 (large tumor suppressor kinase 2) and negatively regulates Hippo signaling leading to increased activity of YAP (yes-associated protein), the transcriptional effector of the pathway. We also show by double siRNA knockdown that the phenotypes caused by JCAD knockdown require LATS2 and that JCAD is involved in transmission of RhoA mediated signals into the Hippo pathway. In human tissues, we find that the CAD associated lead variant, rs2487928, is associated with expression of JCAD in arteries, including atherosclerotic arteries. Gene co-expression analyses across disease-relevant tissues corroborate our phenotypic findings and support the link between JCAD and Hippo signaling. Conclusions- Our results show that JCAD negatively regulates Hippo signaling in endothelial cells and we suggest that JCAD contributes to atherosclerosis by mediating YAP activity and contributing to endothelial dysfunction. PMID- 29794116 TI - Medicinal cannabis should not be used ahead of approved drugs, says German review. PMID- 29794118 TI - Time to take a stand on nurses' working conditions? PMID- 29794119 TI - Nurse education. AB - EBN Perspectives brings together key issues from the commentaries in one of our nursing topic themes. PMID- 29794115 TI - nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe-/- Mice. AB - OBJECTIVE: Atherosclerosis is a chronic multifactorial and inflammatory disease of large and medium arteries and the leading cause of cardiovascular diseases worldwide. The aim of this study was to investigate whether and how the nSMase2 (type 2-neutral sphingomyelinase), a key enzyme of sphingolipid metabolism, may contribute to the development of atherosclerotic lesions. APPROACH AND RESULTS: The role of nSMase2 in atherosclerosis was investigated in Apoe-/-;Smpd3fro/fro mice, mutant for nSMase2, and in Apoe-/-;Smpd3+/+ mice intraperitoneally injected with GW4869, a pharmacological nSMase2 inhibitor. The defect or inhibition of nSMase2 resulted in a reduction of atherosclerotic lesions and a decrease in macrophage infiltration and lipid deposition, although cholesterolemia remained unchanged. nSMase2 inhibition decreased the inflammatory response of murine endothelial cells to oxLDL (oxidized low-density lipoprotein), as assessed by the significant reduction of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule 1) mRNA expressions and macrophage recruitment. Likewise, in RAW264.7 or in macrophages isolated from Apoe-/-/Smpd3fro/fro or Apoe-/-/Smpd3+/+ mice stimulated by lipopolysaccharides, nSMase2 inhibition resulted in a decrease in the expression of inflammatory molecules. Mechanistically, the anti-inflammatory response resulting from nSMase2 inhibition involves Nrf2 (nuclear factor [erythroid-derived 2]-like 2 or NF-E2-related factor-2) activation in both endothelial cells and macrophages, as assessed by the lack of protective effect of GW4869 in endothelial cells silenced for Nrf2 by small interfering RNAs, and in lipopolysaccharide-stimulated macrophages issued from Nrf2-KO mice. CONCLUSIONS: The genetic deficiency or inhibition of nSMase2 strongly decreases the development of atherosclerotic lesions in Apoe-/- mice, by reducing inflammatory responses through a mechanism involving the Nrf2 pathway. Inhibitors of nSMase2 may, therefore, constitute a novel approach to slow down atherosclerosis progression. PMID- 29794120 TI - Mobilising identity through social media: psychosocial support for young people with life-limiting conditions. AB - EBN engages readers through a range of Online social media activities to debate issues important to nurses and nursing. EBN Opinion papers highlight and expand on these debates. PMID- 29794117 TI - Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity. AB - Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV 1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development. PMID- 29794121 TI - Prehospital emergency anaesthesia: an updated survey of UK practice with emphasis on the role of standardisation and checklists. AB - INTRODUCTION: Prehospital emergency anaesthesia (PHEA or 'prehospital rapid sequence intubation') is a high-risk procedure. Standard operating procedures (SOPs) and checklists within healthcare systems have been demonstrated to reduce human error and improve patient safety. We aimed to describe the current practice of PHEA in the UK, determine the use of checklists for PHEA and describe the content, format and layout of any such checklists currently used in the UK. METHOD: A survey of UK prehospital teams was conducted to establish the incidence and conduct of PHEA practice. Results were grouped into systems delivering a high volume of PHEA per year (>50 PHEAs) and low volume (<=50 PHEAs per annum). Standard and 'crash' (immediate) induction checklists were reviewed for length, content and layout. RESULTS: 59 UK physician-led prehospital services were identified of which 43 (74%) participated. Thirty services (70%) provide PHEA and perform approximately 1629 PHEAs annually. Ten 'high volume' services deliver 84% of PHEAs per year with PHEA being performed on a median of 11% of active missions. The most common indication for PHEA was trauma. 25 of the 30 services (83%) used a PHEA checklist prior to induction of anaesthesia and 24 (80%) had an SOP for the procedure. 19 (76%) of the 'standard' checklists and 5 (50%) of the 'crash' induction checklists used were analysed. On average, standard checklists contained 169 (range: 52-286) words and 41 (range: 28-70) individual checks. The style and language complexity varied significantly between different checklists. CONCLUSION: PHEA is now performed commonly in the UK. The use of checklists for PHEA is relatively common among prehospital systems delivering this intervention. Care must be taken to limit checklist length and to use simple, unambiguous language in order to maximise the safety of this high-risk intervention. PMID- 29794122 TI - An Assessment of Asthma Therapy in the Pediatric ICU. AB - OBJECTIVES: To describe asthma management, investigate practice variation, and describe asthma-associated charges and resource use during asthma management in the PICU. METHODS: Children ages 2 to 18 years treated for status asthmaticus in the PICU from 2008 to 2011 are included in this study. This is a retrospective, single-center, cohort study. Data were collected by using the Intermountain Healthcare Enterprise Data Warehouse. RESULTS: There were 262 patients included and grouped by maximal respiratory support intervention. Seventy percent of the patients did not receive escalation of respiratory support beyond nasal cannula or nonrebreather mask, and the majority of these patients received only first tier recommended therapy. For all patients, medical imaging and laboratory charge fractions accounted for <3% and <5% of the total charges, respectively. Among nonintubated patients, the majority of these diagnostic test results were normal. Fifteen patients were intubated during our study period; 4 were intubated at our facility. Compared with outside hospital intubations, these 4 patients had longer time to intubation (>3 days versus <24 hours) and significantly longer median PICU length of stay (12.7 days versus 2.6 days). CONCLUSIONS: In our study, the vast majority of patients with severe asthma were treated with minimal interventions alone (nasal cannula or nonrebreather mask and first-tier medications). Minimizing PICU length of stay is likely the most successful way to decrease expense during asthma care. PMID- 29794123 TI - Comparing the use and timing of palliative care services in COPD and lung cancer: a population-based survey. PMID- 29794124 TI - Partitioning of pulmonary vascular resistances in group 2 pulmonary hypertension: insightful suggestions for bridging haemodynamics to underlying mechanisms. PMID- 29794125 TI - Aminopeptidase antibodies in mesothelioma: new wine deserves new sacks. PMID- 29794129 TI - Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in the USA. PMID- 29794127 TI - Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model. AB - The neurodegenerative disease Friedreich's ataxia is caused by lower than normal levels of frataxin, an important protein involved in iron-sulfur (Fe-S) cluster biogenesis. An important step in designing strategies to treat this disease is to understand whether increasing the frataxin levels by gene therapy would simply be beneficial or detrimental, because previous studies, mostly based on animal models, have reported conflicting results. Here, we have exploited an inducible model, which we developed using the CRISPR/Cas9 methodology, to study the effects of frataxin overexpression in human cells and monitor how the system recovers after overexpression. Using new tools, which range from high-throughput microscopy to in cell infrared, we prove that overexpression of the frataxin gene affects the cellular metabolism. It also leads to a significant increase of oxidative stress and labile iron pool levels. These cellular alterations are similar to those observed when the gene is partly silenced, as occurs in Friedreich's ataxia patients. Our data suggest that the levels of frataxin must be tightly regulated and fine-tuned, with any imbalance leading to oxidative stress and toxicity. PMID- 29794126 TI - Advances in adrenal tumors 2018. AB - This review aims to provide clinicians and researchers with a condensed update on the most important studies in the field during 2017. We present the academic output measured by active clinical trials and peer-reviewed published manuscripts. The most important and contributory manuscripts were summarized for each diagnostic entity, with a particular focus on manuscripts that describe translational research that have the potential to improve clinical care. Finally, we highlight the importance of collaborations in adrenal tumor research, which allowed for these recent advances and provide structures for future success in this scientific field. PMID- 29794128 TI - A Single-Cell Transcriptome Atlas of the Mouse Glomerulus. AB - Background Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown.Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli.Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations.Conclusions Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease. PMID- 29794130 TI - Home spirometry in bronchiolitis obliterans after allogeneic haematopoietic cell transplant. PMID- 29794131 TI - Multi-omic molecular profiling of lung cancer in COPD. AB - Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer. PMID- 29794132 TI - The construction and validation of the Severe Asthma Questionnaire. AB - The US Food and Drug Administration's procedure for scale validation requires a documented stepwise process of qualitative and quantitative data. The aim of this paper is to provide final quantitative validating data for the Severe Asthma Questionnaire (SAQ).The SAQ, Asthma Control Test, Mini Asthma Quality of Life Questionnaire and EQ-5D-5L were completed by 160 patients attending a severe asthma clinic; 51 patients completed the SAQ on two occasions for test-retest reliability analysis. The SAQ produces two scores, a SAQ score based on the average of 16 items and a SAQ-global score from a single 100-point global quality of life scale.Construct validity was demonstrated by factor analysis of the 16 items, convergent validity by correlations of >0.6 between the SAQ, SAQ-global and other questionnaires, and discriminant validity by the ability of the SAQ and SAQ-global to distinguish between different treatment levels. Test-retest reliability (intra-class correlation) was 0.93 for the SAQ and 0.93 for the SAQ global, and the alpha coefficient for the SAQ was 0.93.The SAQ was developed using recommended qualitative and quantitative procedures for scale development, and can be used to gain insight into patients' perceptions of how severe asthma and its treatment affects their lives. PMID- 29794133 TI - Screening for tuberculosis in migrants and visitors from high-incidence settings: present and future perspectives. AB - In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals.This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination country via application for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored. PMID- 29794135 TI - General method for rapid purification of native chromatin fragments. AB - Biochemical, proteomic, and epigenetic studies of chromatin rely on the ability to efficiently isolate native nucleosomes in high yield and purity. However, isolation of native chromatin suitable for many downstream experiments remains a challenging task. This is especially true for the budding yeast Saccharomyces cerevisiae, which continues to serve as an important model organism for the study of chromatin structure and function. Here, we developed a time- and cost efficient universal protocol for isolation of native chromatin fragments from yeast, insect, and mammalian cells. The resulting protocol preserves histone posttranslational modification in the native chromatin state and is applicable for both parallel multisample spin-column purification and large-scale isolation. This protocol is based on the efficient and stable purification of polynucleosomes and features a combination of optimized cell lysis and purification conditions, three options for chromatin fragmentation, and a novel ion-exchange chromatographic purification strategy. The procedure will aid chromatin researchers interested in isolating native chromatin material for biochemical studies and serve as a mild, acid- and detergent-free sample preparation method for MS analysis. PMID- 29794134 TI - Molecular basis for the loss-of-function effects of the Alzheimer's disease associated R47H variant of the immune receptor TREM2. AB - Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on the surface of microglia, macrophages, dendritic cells, and osteoclasts. The R47H TREM2 variant is a significant risk factor for late-onset Alzheimer's disease (AD), and the molecular basis of R47H TREM2 loss of function is an emerging area of TREM2 biology. Here, we report three high-resolution structures of the extracellular ligand-binding domains (ECDs) of R47H TREM2, apo WT, and phosphatidylserine (PS)-bound WT TREM2 at 1.8, 2.2, and 2.2 A, respectively. The structures reveal that Arg47 plays a critical role in maintaining the structural features of the complementarity-determining region 2 (CDR2) loop and the putative positive ligand-interacting surface (PLIS), stabilizing conformations capable of ligand interaction. This is exemplified in the PS-bound structure, in which the CDR2 loop and PLIS drive critical interactions with PS via surfaces that are disrupted in the variant. Together with in vitro and in vivo characterization, our structural findings elucidate the molecular mechanism underlying loss of ligand binding, putative oligomerization, and functional activity of R47H TREM2. They also help unravel how decreased in vitro and in vivo stability of TREM2 contribute to loss of function in disease. PMID- 29794136 TI - The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells. AB - Formation of the vasculature by angiogenesis is critical for proper development, but angiogenesis also contributes to the pathogenesis of various disorders, including cancer and cardiovascular diseases. Vascular endothelial zinc finger 1 (Vezf1), is a Kruppel-like zinc finger protein that plays a vital role in vascular development. However, the mechanism by which Vezf1 regulates this process is not fully understood. Here, we show that Vezf1-/- mouse embryonic stem cells (ESC) have significantly increased expression of a stem cell factor, Cbp/p300-interacting transactivator 2 (Cited2). Compared with WT ESCs, Vezf1-/- ESCs inefficiently differentiated into endothelial cells (ECs), which exhibited defects in the tube-formation assay. These defects were due to reduced activation of EC-specific genes concomitant with lower enrichment of histone 3 acetylation at Lys27 (H3K27) at their promoters. We hypothesized that overexpression of Cited2 in Vezf1-/- cells sequesters P300/CBP away from the promoters of proangiogenic genes and thereby contributes to defective angiogenesis in these cells. This idea was supported by the observation that shRNA-mediated depletion of Cited2 significantly reduces the angiogenic defects in the Vezf1-/- ECs. In contrast to previous studies that have focused on the role of Vezf1 as a transcriptional activator of proangiogenic genes, our findings have revealed a role for Vezf1 in modulating the expression of the antiangiogenic factor Cited2. Vezf1 previously has been characterized as an insulator protein, and our results now provide insights into the mechanism, indicating that Vezf1 can block inappropriate, nonspecific interactions of promoters with cis-located enhancers, preventing aberrant promoter activation. PMID- 29794137 TI - Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. AB - 5-Methoxytryptophan (5-MTP) is a tryptophan metabolite with recently discovered anti-inflammatory and tumor-suppressing activities. Its synthesis is catalyzed by a hydroxyindole O-methyltransferase (HIOMT)-like enzyme. However, the exact identity of this HIOMT in human cells remains unclear. Human HIOMT exists in several alternatively spliced isoforms, and we hypothesized that 5-MTP-producing HIOMT is a distinct isoform. Here, we show that human fibroblasts and cancer cells express the HIOMT298 isoform as contrasted with the expression of the HIOMT345 isoform in pineal cells. Sequencing analysis of the cloned isoforms revealed that HIOMT298 is identical to the sequence of a previously reported truncated HIOMT isoform. Of note, HIOMT298 expression was reduced in cancer cells and tissues. Stable transfection of A549 cancer cells with HIOMT298 restored HIOMT expression to normal levels, accompanied by 5-MTP production. Furthermore, HIOMT298 transfection caused a tryptophan-metabolic switch from serotonin to 5 MTP production. To determine the in vivo relevance of this alteration, we compared growth and lung metastasis of HIOMT298-transfected A549 cells with those of vector- or untransfected A549 cells as controls in a murine xenograft model. Of note, the HIOMT298-transfected A549 cells exhibited slower growth and lower metastasis than the controls. Our findings provide insight into the crucial role of HIOMT298 in 5-MTP production in cells and in inhibiting cancer progression and highlight the potential therapeutic value of 5-MTP for managing cancer. PMID- 29794139 TI - What I got wrong about shelterin. AB - The ASBMB 2018 Bert and Natalie Vallee award in Biomedical Sciences honors our work on shelterin, a protein complex that helps cells distinguish the chromosome ends from sites of DNA damage. Shelterin protects telomeres from all aspects of the DNA damage response, including ATM and ATR serine/threonine kinase signaling and several forms of double-strand break repair. Today, this six-subunit protein complex could easily be identified in one single proteomics step. But, it took us more than 15 years to piece together the entire shelterin complex, one protein at a time. Although we did a lot of things right, here I tell the story of shelterin's discovery with an emphasis on the things that I got wrong along the way. PMID- 29794138 TI - Decline in arylsulfatase B expression increases EGFR expression by inhibiting the protein-tyrosine phosphatase SHP2 and activating JNK in prostate cells. AB - Epidermal growth factor receptor (EGFR) has a crucial role in cell differentiation and proliferation and cancer, and its expression appears to be up regulated when arylsulfatase B (ARSB or GalNAc-4-sulfatase) is reduced. ARSB removes 4-sulfate groups from the nonreducing end of dermatan sulfate and chondroitin 4-sulfate (C4S), and its decreased expression has previously been reported to inhibit the activity of the ubiquitous protein-tyrosine phosphatase, nonreceptor type 11 (SHP2 or PTPN11). However, the mechanism by which decline in ARSB leads to decline in SHP2 activity is unclear. Here, we show that SHP2 binds preferentially C4S, rather than chondroitin 6-sulfate, and confirm that SHP2 activity declines when ARSB is silenced. The reduction in ARSB activity, and the resultant increase in C4S, increased the expression of EGFR (Her1/ErbB1) in human prostate stem and epithelial cells. The increased expression of EGFR occurred after 1) the decline in SHP2 activity, 2) enhanced c-Jun N-terminal kinase (JNK) activity, 3) increased nuclear DNA binding by c-Jun and c-Fos, and 4) EGFR promoter activation. In response to exogenous EGF, there was increased bromodeoxyuridine incorporation, consistent with enhanced cell proliferation. These findings indicated that ARSB and chondroitin 4-sulfation affect the activation of an important dual phosphorylation threonine-tyrosine kinase and the mRNA expression of a critical tyrosine kinase receptor in prostate cells. Restoration of ARSB activity with the associated reduction in C4S may provide a new therapeutic approach for managing malignancies in which EGFR-mediated tyrosine kinase signaling pathways are active. PMID- 29794141 TI - Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep. AB - OBJECTIVE: We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early life postnatal overnutrition modulates implications of prenatal programming. DESIGN: Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months of-age, twin lambs received a conventional (CONV) or an obesogenic, high carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 21/2 years-of-age (adulthood). METHODS: Serum hormone levels were determined at 6 months- and 21/2 years-of-age. At 21/2 years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). RESULTS: In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk. PMID- 29794140 TI - The stimulatory G protein Gsalpha is required in melanocortin 4 receptor expressing cells for normal energy balance, thermogenesis, and glucose metabolism. AB - Central melanocortin 4 receptors (MC4Rs) stimulate energy expenditure and inhibit food intake. MC4Rs activate the G protein Gsalpha, but whether Gsalpha mediates all MC4R actions has not been established. Individuals with Albright hereditary osteodystrophy (AHO), who have heterozygous Gsalpha-inactivating mutations, only develop obesity when the Gsalpha mutation is present on the maternal allele because of tissue-specific genomic imprinting. Furthermore, evidence in mice implicates Gsalpha imprinting within the central nervous system (CNS) in this disorder. In this study, we examined the effects of Gsalpha in MC4R-expressing cells on metabolic regulation. Mice with homozygous Gsalpha deficiency in MC4R expressing cells (MC4RGsKO) developed significant obesity with increased food intake and decreased energy expenditure, along with impaired insulin sensitivity and cold-induced thermogenesis. Moreover, the ability of the MC4R agonist melanotan-II (MTII) to stimulate energy expenditure and to inhibit food intake was impaired in MC4RGsKO mice. MTII failed to stimulate the secretion of the anorexigenic hormone peptide YY (PYY) from enteroendocrine L cells, a physiological response mediated by MC4R-Gsalpha signaling, even though baseline PYY levels were elevated in these mice. In Gsalpha heterozygotes, mild obesity and reduced energy expenditure were present only in mice with a Gsalpha deletion on the maternal allele in MC4R-expressing cells, whereas food intake was unaffected. These results demonstrate that Gsalpha signaling in MC4R-expressing cells is required for controlling energy balance, thermogenesis, and peripheral glucose metabolism. They further indicate that Gsalpha imprinting in MC4R expressing cells contributes to obesity in Gsalpha knockout mice and probably in individuals with Albright hereditary osteodystrophy as well. PMID- 29794142 TI - Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. AB - In contrast to venous thromboembolism, little is known about arterial thromboembolism in patients with cancer. The aim of this study was to quantify the risk and explore clinical risk factors of arterial thromboembolism in patients with cancer, and investigate its potential impact on mortality. Patients with newly-diagnosed cancer or progression of disease after remission were included in a prospective observational cohort study and followed for two years. Between October 2003 and October 2013, 1880 patients (54.3% male; median age 61 years) were included. During a median follow up of 723 days, 48 (2.6%) patients developed arterial thromboembolism [20 (41.7%) myocardial infarction, 16 (33.3%) stroke and 12 (25.0%) peripheral arterial events], 157 (8.4%) developed venous thromboembolism, and 754 (40.1%) patients died. The cumulative 3-, 6-, 12-, and 24-month risks of arterial thromboembolism were 0.9%, 1.1%, 1.7%, and 2.6%, respectively. Male sex (subdistribution hazard ratio=2.9, 95%CI: 1.5-5.6; P=0.002), age (subdistribution hazard ratio per 10 year increase=1.5, 1.2-1.7; P<0.001), hypertension (3.1, 1.7-5.5; P<0.001), smoking (2.0, 1.1-3.7; P=0.022), lung cancer (2.3, 1.2-4.2; P=0.009), and kidney cancer (3.8, 1.4-10.5; P=0.012) were associated with a higher arterial thromboembolism risk. Furthermore, the occurrence of arterial thromboembolism was associated with a 3.2-fold increased risk of all-cause mortality (hazard ratio=3.2, 95%CI: 2.2-4.8; P<0.001). Arterial thromboembolism is a less common complication in patients with cancer than venous thromboembolism. The risk of arterial thromboembolism is high in patients with lung and kidney cancer. Patients with cancer who develop arterial thromboembolism are at a 3-fold increased risk of mortality. PMID- 29794144 TI - Contribution of alternative complement pathway to delayed hemolytic transfusion reaction in sickle cell disease. PMID- 29794145 TI - Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma. PMID- 29794143 TI - Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective. AB - Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curacao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered via a multidisciplinary approach with appropriate diagnosis, screening and local and/or systemic management of lesions. Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment. PMID- 29794146 TI - Phase 3 results for vosaroxin/cytarabine in the subset of patients >=60 years old with refractory/early relapsed acute myeloid leukemia. PMID- 29794147 TI - Reducing mortality in newly diagnosed standard-risk acute promyelocytic leukemia in elderly patients treated with arsenic trioxide requires major reduction of chemotherapy: a report by the French Belgian Swiss APL group (APL 2006 trial). PMID- 29794148 TI - Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality - a pooled patient data analysis of 16 observational trials. AB - Observational studies address packed red blood cell effects at the end of shelf life and have larger sample sizes compared to randomized control trials. Meta analyses combining data from observational studies have been complicated by differences in aggregate transfused packed red blood cell age and outcome reporting. This study abrogated these issues by taking a pooled patient data approach. Observational studies reporting packed red blood cell age and clinical outcomes were identified and patient-level data sets were sought from investigators. Odds ratios and 95% confidence intervals for binary outcomes were calculated for each study, with mean packed red blood cell age or maximum packed red blood cell age acting as independent variables. The relationship between mean packed red blood cell age and hospital length of stay for each paper was analyzed using zero-inflated Poisson regression. Random effects models combined paper level effect estimates. Extremes analyses were completed by comparing patients transfused with mean packed red blood cell aged less than ten days to those transfused with mean packed red blood cell aged at least 30 days. sixteen datasets were available for pooled patient data analysis. Mean packed red blood cell age of at least 30 days was associated with an increased risk of in-hospital mortality compared to mean packed red blood cell of less than ten days (odds ratio: 3.25, 95% confidence interval: 1.27-8.29). Packed red blood cell age was not correlated to increased risks of nosocomial infection or prolonged length of hospital stay. PMID- 29794149 TI - NLRP3 regulates platelet integrin alphaIIbbeta3 outside-in signaling, hemostasis and arterial thrombosis. AB - In addition to their hemostatic function, platelets play an important role in regulating the inflammatory response. The platelet NLRP3 inflammasome not only promotes interleukin-1beta secretion, but was also found to be upregulated during platelet activation and thrombus formation in vitro However, the role of NLRP3 in platelet function and thrombus formation in vivo remains unclear. In this study, we aimed to investigate the role of NLRP3 in platelet integrin alphaIIbbeta3 signaling transduction. Using NLRP3-/- mice, we showed that NLRP3-deficient platelets do not have significant differences in expression of the platelet specific adhesive receptors alphaIIbbeta3 integrin, GPIba or GPVI; however, NLRP3 /- platelets transfused into wild-type mice resulted in prolonged tail-bleeding time and delayed arterial thrombus formation, as well as exhibiting impaired spreading on immobilized fibrinogen and defective clot retraction, concomitant with decreased phosphorylation of c-Src, Syk and PLCgamma2 in response to thrombin stimulation. Interestingly, addition of exogenous recombinant interleukin-1beta reversed the defect in NLRP3-/- platelet spreading and clot retraction, and restored thrombin-induced phosphorylation of c-Src/Syk/PLCgamma2, whereas an anti-interleukin-1beta antibody blocked spreading and clot retraction mediated by wild-type platelets. Using the direct NLRP3 inhibitor, CY-09, we demonstrated significantly reduced human platelet aggregation in response to threshold concentrations of collagen and ADP, as well as impaired clot retraction in CY-09-treated human platelets, supporting a role for NLRP3 also in regulating human platelet alphaIIbbeta3 outside-in signaling. This study identifies a novel role for NLRP3 and interleukin-1beta in platelet function, and provides a new potential link between thrombosis and inflammation, suggesting that therapies targeting NLRP3 or interleukin-1beta might be beneficial for treating inflammation-associated thrombosis. PMID- 29794151 TI - National Rates of Initiation and Intensification of Antidiabetic Therapy Among Patients With Commercial Insurance. AB - OBJECTIVE: Prompt initiation and intensification of antidiabetic therapy can delay or prevent complications from diabetes. We sought to understand the rates of and factors associated with the initiation and intensification of antidiabetic therapy among commercially insured patients in the U.S. RESEARCH DESIGN AND METHODS: Using 2008-2015 commercial claims linked with laboratory and pharmacy data, we created an initiation cohort with no prior antidiabetic drug use and an HbA1c >=8% (64 mmol/mol) and an intensification cohort of patients with an HbA1c >=8% (64 mmol/mol) who were on a stable dose of one noninsulin diabetes drug. Using multivariable logistic regression, we determined the rates of and factors associated with initiation and intensification. In addition, we determined the percent of variation in treatment patterns explained by measurable patient factors. RESULTS: In the initiation cohort (n = 9,799), 63% of patients received an antidiabetic drug within 6 months of the elevated HbA1c test. In the intensification cohort (n = 10,941), 82% had their existing antidiabetic therapy intensified within 6 months of the elevated HbA1c test. Higher HbA1c levels, lower generic drug copayments, and more frequent office visits were associated with higher rates of both initiation and intensification. Better patient adherence prior to the elevated HbA1c level, existing therapy with a second generation antidiabetic drug, and lower doses of existing therapy were also associated with intensification. Patient factors explained 7.96% of the variation in initiation and 7.35% of the variation in intensification. CONCLUSIONS: Approximately two-thirds of patients were newly initiated on antidiabetic therapy, and four-fifths of those already receiving antidiabetic therapy had it intensified within 6 months of an elevated HbA1c in a commercially insured population. Patient factors explain 7-8% of the variation in diabetes treatment patterns. PMID- 29794150 TI - ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability. AB - The human zinc metalloprotease ZMPSTE24 is an integral membrane protein crucial for the final step in the biogenesis of the nuclear scaffold protein lamin A, encoded by LMNA After farnesylation and carboxyl methylation of its C-terminal CAAX motif, the lamin A precursor (prelamin A) undergoes proteolytic removal of its modified C-terminal 15 amino acids by ZMPSTE24. Mutations in LMNA or ZMPSTE24 that impede this prelamin A cleavage step cause the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS), and the related progeroid disorders mandibuloacral dysplasia type B (MAD-B) and restrictive dermopathy (RD). Here, we report the development of a 'humanized yeast system' to assay ZMPSTE24-dependent cleavage of prelamin A and examine the eight known disease-associated ZMPSTE24 missense mutations. All mutations show diminished prelamin A processing and fall into three classes, with defects in activity, protein stability or both. Notably, some ZMPSTE24 mutants can be rescued by deleting the E3 ubiquitin ligase Doa10, involved in endoplasmic reticulum (ER)-associated degradation of misfolded membrane proteins, or by treatment with the proteasome inhibitor bortezomib. This finding may have important therapeutic implications for some patients. We also show that ZMPSTE24-mediated prelamin A cleavage can be uncoupled from the recently discovered role of ZMPSTE24 in clearance of ER membrane translocon clogged substrates. Together with the crystal structure of ZMPSTE24, this humanized yeast system can guide structure-function studies to uncover mechanisms of prelamin A cleavage, translocon unclogging, and membrane protein folding and stability. PMID- 29794153 TI - Research or clinical care: what's the difference? PMID- 29794154 TI - Ethics briefing. PMID- 29794155 TI - Global conformational changes in IgG-Fc upon mutation of the FcRn-binding site are not associated with altered antibody-dependent effector functions. AB - Antibody engineering is important for many diagnostic and clinical applications of monoclonal antibodies. We recently reported a series of fragment crystallizable (Fc) mutations targeting the neonatal Fc receptor (FcRn) site on a Lewis Y (Ley) binding IgG1, hu3S193. The hu3S193 variants displayed shortened in vivo half-lives and may have potential for radioimaging or radiotherapy of Ley positive tumors. Here, we report Fc crystal structures of wild-type hu3S193, seven FcRn-binding site variants, and a variant lacking C1q binding or complement dependent cytotoxicity (CDC) activity. The Fc conformation of the FcRn-binding sites was similar for wild-type and all mutants of hu3S193 Fc, which suggests that FcRn interactions were directly affected by the amino acid substitutions. The C1q-binding site mutant Fc was nearly identical with the wild-type Fc. Surprisingly, several hu3S193 Fc variants showed large changes in global structure compared with wild-type Fc. All hu3S193 Fc mutants had similar antibody dependent cellular cytotoxicity, despite some with conformations expected to diminish Fc gamma receptor binding. Several hu3S193 variants displayed altered CDC, but there was no correlation with the different Fc conformations. All versions of hu3S193, except the C1q-binding site mutant, bound C1q, suggesting that the altered CDC of some variants could result from different propensities to form IgG hexamers after engaging Ley on target cells. Overall, our findings support the concept that the antibody Fc is both flexible and mobile in solution. Structure-based design approaches should take into account the conformational plasticity of the Fc when engineering antibodies with optimal effector properties. PMID- 29794157 TI - A novel combined approach using a Penumbra catheter and balloon catheter for cerebral venous sinus thrombosis. AB - Cerebral venous sinus thrombosis is sometimes fatal. We describe a case of sinus thrombosis in a 43-year-old woman presenting with generalized seizure, delirium, and a 2 week history of headache and nausea. The patient underwent mechanical thrombectomy using a novel combined approach, in which a Shouryu HR balloon catheter (Kaneka) was anchored in the right transverse sinus (TS), sigmoid sinus (SS), and superior sagittal sinus (SSS), while a Penumbra 5 MAX ACE (Penumbra) catheter was moved back and forth between the right TS, SS, and SSS. Additionally, back and forth movement of the inflated balloon with aspiration-the so-called 'dental floss technique'-was performed. Partial recanalization was eventually obtained. Follow-up angiography on postoperative day 7 showed a dramatic improvement in venous outflow. The patient was transferred to a rehabilitation hospital on postoperative day 42. We describe our combined approach using aspiration, and Penumbra and balloon catheters, to achieve mechanical thrombectomy for sinus thrombosis. PMID- 29794158 TI - Mechanical thrombectomy for repeated cerebral tumor embolism from a thoracic sarcomatoid carcinoma. AB - Cerebral embolism originating from intracardiac tumors represents a rare cause of stroke and has been documented in both adult and pediatric populations. We present a patient recently diagnosed with a right pulmonary hilum tumor, invading the pulmonary veins and the left atrium. Two consecutive episodes of large cerebral vessel occlusion in separate vascular territories occurred in the same day and were treated by mechanical thrombectomy. Embolic material retrieved on both occasions contained tumor fragments with peripheral endothelialization. To our knowledge, this is the first report with histological confirmation of cerebral embolism from an invasive extracardiac tumor. PMID- 29794160 TI - Recurrence of a totally occluded aneurysm after treatment with a pipeline embolization device. AB - Treatment with a pipeline embolization device (PED) is widely accepted as an excellent option for patients harboring giant, wide neck, saccular intracranial aneurysms. It has been shown to be safe and very effective. We describe a previously unreported case of a large middle cerebral artery aneurysm, related to the carotid tip, that was treated with a PED and coils. The 6 month follow-up angiogram demonstrated complete occlusion of the aneurysm. However, the 9 month angiogram revealed recurrent filling of the aneurysm sac. To our knowledge, this is the first report to describe recanalization of an aneurysm totally occluded on the control angiography after treatment with a PED. Unanswered questions include the mechanism of recanalization and the need for additional control angiograms and MRI following a previous examination revealing total aneurysm occlusion. PMID- 29794156 TI - The beta3-integrin endothelial adhesome regulates microtubule-dependent cell migration. AB - Integrin beta3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely beta3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the beta3-dependent adhesome. We show that depletion of beta3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. beta3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when beta3-integrin levels are reduced. PMID- 29794159 TI - Anatomy of the deep venous system in vein of Galen malformation and its changes after endovascular treatment depicted by magnetic resonance venography. AB - BACKGROUND AND PURPOSE: It is classically thought that the internal cerebral veins (ICV) do not communicate with the venous pouch of vein of Galen malformations (VGM). We report on the anatomy of the deep venous system in VGM with special emphasis on the drainage of the ICV and possible changes after endovascular treatment. MATERIALS AND METHODS: We retrospectively analyzed DSA and 2D time-of-flight MR venograms of 55 children with VGM. We evaluated all pre- and post-operative images for the presence of the ICVs and determined their route of venous drainage. RESULTS: Of 55 children, pre-operative 2D MRV detected the ICVs in 19 cases (35%) compared with one case (2%) for pre-embolization DSA (2%) (P<0.0001). Of the cases in which the ICVs were seen preoperatively, in 15 cases (78.9%) the ICV drained directly into the VGM while in the other four cases, the ICV used alternative venous drainage routes. On post-operative MRV, the ICVs were seen in 17 cases (31%) on MRV and 10 cases (18.2%) on DSA with drainage into an adult-like vein of Galen in 13 cases (76%), respectively (P=0.08). In four cases normal ICV drainage into the vein of Galen was seen even when the venous sac was closed. In two cases there was a change in ICV drainage from the vein of Galen to the lateral mesencephalic vein. CONCLUSION: The communication of the ICV with the VGM is a common phenomenon. Different changes of venous drainage routes do occur after treatment and are best seen on MRV. PMID- 29794161 TI - Fluorocholine Transport Mediated by the Organic Cation Transporter 2 (OCT2, SLC22A2): Implication for Imaging of Kidney Tumors. AB - [18F]fluorocholine is the fluorinated analog of [11C]choline and is used in positron emission tomography to monitor tumor metabolic activity. Although important to optimize its use and expand the clinical indications, the molecular determinants of fluorocholine cellular uptake are poorly characterized. In this work, we described the influx kinetics of fluorocholine mediated by the organic cation transporter 2 (OCT2, SLC22A2) and compared with that of choline. Then we characterized the expression pattern of OCT2 in renal cell carcinoma (RCC). In HEK293 cells stably transfected with OCT2 fluorocholine influx, kinetics was biphasic, suggesting two independent binding sites: a high-affinity (Km = 14 +/- 8 uM, Vmax = 1.3 +/- 0.5 nmol mg-1 min-1) and a low-affinity component (Km = 1.8 +/- 0.3 mM, Vmax = 104 +/- 4.5 nmol mg-1 min-1). Notably, choline was found to be transported with sigmoidal kinetics typical of homotropic positive cooperativity (h = 1.2, 95% confidence interval 1.1-1.3). OCT2 mRNA expression level was found significantly decreased in primary but not in metastatic RCC. Tissue microarray immunostaining of 216 RCC biopsies confirmed that the OCT2 protein level was consistent with that of the mRNA. The kinetic properties described in this work suggest that OCT2 is likely to play a dominant role in [18F]fluorocholine uptake in vivo. OCT2-altered expression in primary and metastatic cancer cells, as compared with the surrounding tissues, could be exploited in RCC imaging, especially to increase the detection sensitivity for small metastatic lesions, a major clinical challenge during the initial staging of RCC. PMID- 29794152 TI - The high-affinity calcium sensor synaptotagmin-7 serves multiple roles in regulated exocytosis. AB - Synaptotagmin (Syt) proteins comprise a 17-member family, many of which trigger exocytosis in response to calcium. Historically, most studies have focused on the isoform Syt-1, which serves as the primary calcium sensor in synchronous neurotransmitter release. Recently, Syt-7 has become a topic of broad interest because of its extreme calcium sensitivity and diversity of roles in a wide range of cell types. Here, we review the known and emerging roles of Syt-7 in various contexts and stress the importance of its actions. Unique functions of Syt-7 are discussed in light of recent imaging, electrophysiological, and computational studies. Particular emphasis is placed on Syt-7-dependent regulation of synaptic transmission and neuroendocrine cell secretion. Finally, based on biochemical and structural data, we propose a mechanism to link Syt-7's role in membrane fusion with its role in subsequent fusion pore expansion via strong calcium-dependent phospholipid binding. PMID- 29794163 TI - Phenotypic Data from Inbred Parents Can Improve Genomic Prediction in Pearl Millet Hybrids. AB - Pearl millet is a non-model grain and fodder crop adapted to extremely hot and dry environments globally. In India, a great deal of public and private sectors' investment has focused on developing pearl millet single cross hybrids based on the cytoplasmic-genetic male sterility (CMS) system, while in Africa most pearl millet production relies on open pollinated varieties. Pearl millet lines were phenotyped for both the inbred parents and hybrids stage. Many breeding efforts focus on phenotypic selection of inbred parents to generate improved parental lines and hybrids. This study evaluated two genotyping techniques and four genomic selection schemes in pearl millet. Despite the fact that 6* more sequencing data were generated per sample for RAD-seq than for tGBS, tGBS yielded more than 2* as many informative SNPs (defined as those having MAF > 0.05) than RAD-seq. A genomic prediction scheme utilizing only data from hybrids generated prediction accuracies (median) ranging from 0.73-0.74 (1000-grain weight), 0.87 0.89 (days to flowering time), 0.48-0.51 (grain yield) and 0.72-0.73 (plant height). For traits with little to no heterosis, hybrid only and hybrid/inbred prediction schemes performed almost equivalently. For traits with significant mid parent heterosis, the direct inclusion of phenotypic data from inbred lines significantly (P < 0.05) reduced prediction accuracy when all lines were analyzed together. However, when inbreds and hybrid trait values were both scored relative to the mean trait values for the respective populations, the inclusion of inbred phenotypic datasets moderately improved genomic predictions of the hybrid genomic estimated breeding values. Here we show that modern approaches to genotyping by sequencing can enable genomic selection in pearl millet. While historical pearl millet breeding records include a wealth of phenotypic data from inbred lines, we demonstrate that the naive incorporation of this data into a hybrid breeding program can reduce prediction accuracy, while controlling for the effects of heterosis per se allowed inbred genotype and trait data to improve the accuracy of genomic estimated breeding values for pearl millet hybrids. PMID- 29794164 TI - The Aspergillus nidulans Pyruvate Dehydrogenase Kinases Are Essential To Integrate Carbon Source Metabolism. AB - The pyruvate dehydrogenase complex (PDH), that converts pyruvate to acetyl-coA, is regulated by pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilization in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in carbon source utilization in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. PkpA and PkpB were shown to be mitochondrial whereas PkpC localized to the mitochondria in a carbon source dependent manner. Only PkpA was shown to regulate PDH activity. In the presence of glucose, deletion of pkpA and pkpC resulted in reduced glucose utilization, which affected carbon catabolite repression (CCR) and hydrolytic enzyme secretion, due to de-regulated glycolysis and TCA cycle enzyme activities. Furthermore, PkpC was shown to be required for the correct metabolic utilization of cellulose and acetate. PkpC negatively regulated the activity of the glyoxylate cycle enzyme isocitrate lyase (ICL), required for acetate metabolism. In summary, this study identified PDHKs important for the regulation of central carbon metabolism in the presence of different carbon sources, with effects on the secretion of biotechnologically important enzymes and carbon source-related growth. This work demonstrates how central carbon metabolism can affect a variety of fungal traits and lays a basis for further investigation into these characteristics with potential interest for different applications. PMID- 29794165 TI - Limited Mutation-Rate Variation Within the Paramecium aurelia Species Complex. AB - Mutation is one of the most fundamental evolutionary forces. Studying variation in the mutation rate within and among closely-related species can help reveal mechanisms of genome divergence, but such variation is unstudied in the vast majority of organisms. Previous studies on ciliated protozoa have found extremely low mutation rates. In this study, using mutation-accumulation techniques combined with deep whole-genome sequencing, we explore the germline base substitution mutation-rate variation of three cryptic species in the Paramecium aurelia species complex-P. biaurelia, P. sexaurelia, and P. tetraurelia We find that there is extremely limited variation of the mutation rate and spectrum in the three species and confirm the extremely low mutation rate of ciliates. PMID- 29794162 TI - Genome-Wide Analysis of Multidrug and Toxic Compound Extrusion (MATE) Family in Gossypium raimondii and Gossypium arboreum and Its Expression Analysis Under Salt, Cadmium, and Drought Stress. AB - The extrusion of toxins and substances at a cellular level is a vital life process in plants under abiotic stress. The multidrug and toxic compound extrusion (MATE) gene family plays a large role in the exportation of toxins and other substrates. We carried out a genome-wide analysis of MATE gene families in Gossypium raimondii and Gossypium arboreum and assessed their expression levels under salt, cadmium and drought stresses. We identified 70 and 68 MATE genes in G. raimondii and G. arboreum, respectively. The majority of the genes were predicted to be localized within the plasma membrane, with some distributed in other cell parts. Based on phylogenetic analysis, the genes were subdivided into three subfamilies, designated as M1, M2 and M3. Closely related members shared similar gene structures, and thus were highly conserved in nature and have mainly evolved through purifying selection. The genes were distributed in all chromosomes. Twenty-nine gene duplication events were detected, with segmental being the dominant type. GO annotation revealed a link to salt, drought and cadmium stresses. The genes exhibited differential expression, with GrMATE18, GrMATE34, GaMATE41 and GaMATE51 significantly upregulated under drought, salt and cadmium stress, and these could possibly be the candidate genes. Our results provide the first data on the genome-wide and functional characterization of MATE genes in diploid cotton, and are important for breeders of more stress-tolerant cotton genotypes. PMID- 29794166 TI - A High Quality Genome for Mus spicilegus, a Close Relative of House Mice with Unique Social and Ecological Adaptations. AB - Genomic data for the closest relatives of house mice (Mus musculus species complex) are surprisingly limited. Here, we present the first complete genome for a behaviorally and ecologically unique member of the sister clade to house mice, the mound-building mouse, Mus spicilegus Using read cloud sequencing and de novo assembly we produced a 2.50 Gbp genome with a scaffold N50 of 2.27 Mbp. We constructed >25 000 gene models, of which the majority had high homology to other Mus species. To evaluate the utility of the M. spicilegus genome for behavioral and ecological genomics, we extracted 196 vomeronasal receptor (VR) sequences from our genome and analyzed phylogenetic relationships between M. spicilegus VRs and orthologs from M. musculus and the Algerian mouse, M. spretus While most M. spicilegus VRs clustered with orthologs in M. musculus and M. spretus, 10 VRs with evidence of rapid divergence in M. spicilegus are strong candidate modulators of species-specific chemical communication. A high quality assembly and genome for M. spicilegus will help to resolve discordant ancestry patterns in house mouse genomes, and will provide an essential foundation for genetic dissection of phenotypes that distinguish commensal from non-commensal species, and the social and ecological characteristics that make M. spicilegus unique. PMID- 29794168 TI - Carbonic Anhydrase Mutants in Zea mays Have Altered Stomatal Responses to Environmental Signals. AB - Stomata regulate transpirational water loss and CO2 uptake for photosynthesis in response to changing environmental conditions. Research investigating stomatal movement has mostly been conducted in C3 eudicot species, which have very different CO2 requirements for photosynthesis relative to C4 grasses. Carbonic anhydrase (CA) catalyzes the hydration of CO2, and its activity has been linked to stomatal aperture regulation in eudicots. The number of Ca genes and their evolutionary history differ between monocots and dicots, and many questions remain unanswered about potential neofunctionalization and subfunctionalization of grass Ca paralogs and their roles in photosynthesis and stomatal conductance. To investigate the roles of different Ca genes in maize (Zea mays), we examined stomatal responses in ca1 and ca2 single mutants as well as a ca1ca2 double mutant. The ca1 and ca2 single mutants had 10% and 87% of the CA activity exhibited by the wild type, respectively, while ca1ca2 had less than 5% of wild type CA activity. The ca mutants had higher stomatal conductance than the wild type and slower stomatal closure in response to increases in CO2 partial pressure. Contrary to previous reports in eudicots, ca mutants showed slowed stomatal closure in response to the light-dark transition and did not show differences in stomatal density compared with the wild type. These results implicate CA-mediated signaling in the control of stomatal movement but not stomatal development. Drought experiments with ca1ca2 mutant plants suggest a role for CA in water-use efficiency and reveal that Z. mays is not optimized for water-use efficiency under well-watered conditions. PMID- 29794167 TI - Genomic Selection for Late Blight and Common Scab Resistance in Tetraploid Potato (Solanum tuberosum). AB - Potato (Solanum tuberosum) is a staple food crop and is considered one of the main sources of carbohydrates worldwide. Late blight (Phytophthora infestans) and common scab (Streptomyces scabies) are two of the primary production constraints faced by potato farming. Previous studies have identified a few resistance genes for both late blight and common scab; however, these genes explain only a limited fraction of the heritability of these diseases. Genomic selection has been demonstrated to be an effective methodology for breeding value prediction in many major crops (e.g., maize and wheat). However, the technology has received little attention in potato breeding. We present the first genomic selection study involving late blight and common scab in tetraploid potato. Our data involves 4,110 (Single Nucleotide Polymorphisms, SNPs) and phenotypic field evaluations for late blight (n=1,763) and common scab (n=3,885) collected in seven and nine years, respectively. We report moderately high genomic heritability estimates (0.46 +/- 0.04 and 0.45 +/- 0.017, for late blight and common scab, respectively). The extent of genotype-by-year interaction was high for late blight and low for common scab. Our assessment of prediction accuracy demonstrates the applicability of genomic prediction for tetraploid potato breeding. For both traits, we found that more than 90% of the genetic variance could be captured with an additive model. For common scab, the highest prediction accuracy was achieved using an additive model. For late blight, small but statistically significant gains in prediction accuracy were achieved using a model that accounted for both additive and dominance effects. Using whole-genome regression models we identified SNPs located in previously reported hotspots regions for late blight, on genes associated with systemic disease resistance responses, and a new locus located in a WRKY transcription factor for common scab. PMID- 29794170 TI - Who does TORC2 talk to? AB - The target of rapamycin (TOR) is a protein kinase that, by forming complexes with partner proteins, governs diverse cellular signalling networks to regulate a wide range of processes. TOR thus plays central roles in maintaining normal cellular functions and, when dysregulated, in diverse diseases. TOR forms two distinct types of multiprotein complexes (TOR complexes 1 and 2, TORC1 and TORC2). TORC1 and TORC2 differ in their composition, their control and their substrates, so that they play quite distinct roles in cellular physiology. Much effort has been focused on deciphering the detailed regulatory links within the TOR pathways and the structure and control of TOR complexes. In this review, we summarize recent advances in understanding mammalian (m) TORC2, its structure, its regulation, and its substrates, which link TORC2 signalling to the control of cell functions. It is now clear that TORC2 regulates several aspects of cell metabolism, including lipogenesis and glucose transport. It also regulates gene transcription, the cytoskeleton, and the activity of a subset of other protein kinases. PMID- 29794169 TI - DDM1 Represses Noncoding RNA Expression and RNA-Directed DNA Methylation in Heterochromatin. AB - C methylation of DNA, which occurs at CG, CHG, and CHH (H = A, C, or T) sequences in plants, is a hallmark for the epigenetic repression of repetitive sequences. The chromatin-remodeling factor DECREASE IN DNA METHYLATION1 (DDM1) is essential for DNA methylation, especially at CG and CHG sequences. However, its potential roles in RNA-directed DNA methylation (RdDM) and in chromatin function are not completely understood in rice (Oryza sativa). In this work, we used high throughput approaches to study the function of rice DDM1 (OsDDM1) in RdDM and the expression of noncoding RNA. We show that loss of function of OsDDM1 results in ectopic CHH methylation of transposable elements and repeats. The ectopic CHH methylation was dependent on rice DOMAINS REARRANGED METHYLTRANSFERASE2, a DNA methyltransferase involved in RdDM. Mutations in OsDDM1 lead to decreases of histone H3K9me2 and increases in the levels of heterochromatic small RNA and long noncoding RNA. In particular, OsDDM1 was found to be essential to repress the transcription of the two repetitive sequences, Centromeric Retrotransposons of Rice1 and the dominant centromeric CentO repeats. These results suggest that OsDDM1 antagonizes RdDM at heterochromatin and represses the tissue-specific expression of noncoding RNA from repetitive sequences in the rice genome. PMID- 29794171 TI - Emergent management of the suspected pelvic fracture: challenges in the obese patient. AB - Pelvic fractures, although infrequent, are a significant cause of morbidity and mortality in the trauma population. Currently, the mainstay of emergent management of a suspected pelvic fracture is placement of a pelvic binder, and their use in the prehospital setting is recommended for any individual involved in high-energy trauma. Obesity in the trauma patient has been shown to be an independent risk factor of morbidity and mortality, and the incidence of pelvic and lower extremity fractures has consistently demonstrated to be higher in the obese patient compared with an individual with a normal body habitus. This article aims to highlight the challenges associated with pelvic fracture in the obese population. PMID- 29794172 TI - Experimental platforms to study blast injury. AB - Injuries sustained due to attacks from explosive weapons are multiple in number, complex in nature, and not well characterised. Blast may cause damage to the human body by the direct effect of overpressure, penetration by highly energised fragments, and blunt trauma by violent displacements of the body. The ability to reproduce the injuries of such insults in a well-controlled fashion is essential in order to understand fully the unique mechanism by which they occur, and design better treatment and protection strategies to alleviate the resulting poor long term outcomes. This paper reports a range of experimental platforms that have been developed for different blast injury models, their working mechanism, and main applications. These platforms include the shock tube, split-Hopkinson bars, the gas gun, drop towers and bespoke underbody blast simulators. PMID- 29794173 TI - John Douglas Parkinson. AB - A likeable practitioner - ferociously intelligent, fair minded and with strong principles - he was one of the last veterinary surgeons who saw action in the Second World War. PMID- 29794174 TI - Welfare: are we heading to a golden age? PMID- 29794175 TI - Insurer partners with 'cheap' drugs supplier. PMID- 29794177 TI - Government set to consult on puppy trade. PMID- 29794178 TI - Tackling bovine TB in Northern Ireland. PMID- 29794179 TI - Alliance to develop future leaders in agri-food. PMID- 29794181 TI - Dispelling the myths of animal-assisted care. AB - The use of animals in healthcare settings can have many benefits, but some people are worried about their use. Now, as Georgina Mills explains, the nursing profession is helping to ease concern. PMID- 29794185 TI - 'Animal welfare is core to the role of every vet'. AB - Sean Wensley's name has become synonymous with animal welfare reform. Here, the BVA council member and former president of the association tells Adele Waters where his ambition for better welfare began and where he hopes it may lead. PMID- 29794186 TI - Pet owners turn to the internet for advice: will vets be there to provide an information prescription? PMID- 29794189 TI - Full-time veterinary equivalents. PMID- 29794187 TI - Diagnosis and prevention of RHVD2 infection. PMID- 29794190 TI - Patient safety first. PMID- 29794191 TI - Universities should encourage helmet wearing. PMID- 29794192 TI - BVD eradication. PMID- 29794193 TI - Horses at the Royal wedding. PMID- 29794194 TI - Electric collars and fences. PMID- 29794195 TI - Seized dogs in kennels. PMID- 29794196 TI - Tick bites and tick-transmitted diseases. PMID- 29794201 TI - Clinical Pharmacology of Bronchodilator Medications. AB - Obstructive lung diseases, including asthma and COPD, are characterized by air flow limitation. Bronchodilator therapy can often decrease symptoms of air-flow obstruction by relaxing airway smooth muscle (bronchodilation), decreasing dyspnea, and improving quality of life. In this review, we discuss the pharmacology of the beta agonist and anticholinergic bronchodilators and their use, particularly in asthma and COPD. Expanding knowledge of receptor subtypes and G-protein signaling, agonist and antagonist specificity, and drug delivery have led to the introduction of safer medications with fewer off-target effects, medications with longer duration of action that may improve adherence, and more effective and efficient aerosol delivery devices. PMID- 29794202 TI - Clinical Pharmacology of Corticosteroids. AB - Corticosteroids have numerous applications in treating inflammation and diseases of immune function based on their significant anti-inflammatory and immunosuppressive effects. Corticosteroids modulate immune function through various effects in the nucleus of numerous cells. When used in pharmacologic doses to suppress allergic responses or inflammation, these agents can cause numerous adverse effects associated with an excess of glucocorticoid activity. Prolonged use (>2 wk) results in suppression of the hypothalamic-pituitary adrenal axis, which requires tapering of doses. Dosing strategies for systemic corticosteroids are designed to minimize the risk for hypothalamic-pituitary adrenal axis suppression. Topical administration of corticosteroids, including oral inhalation, is often used to avoid the significant adverse effects associated with chronic use. Inhaled corticosteroids are potent synthetic agents that exert their actions locally in the airways but can cause systemic effects based on several factors that influence systemic bioavailability. Inhaled corticosteroids are the cornerstone of asthma therapy and important options for COPD in patients who experience frequent exacerbations. By the nasal route, they are the most effective therapy for treating moderate-to-severe allergic rhinitis. PMID- 29794205 TI - Current and Emerging Biologic Therapies for Asthma and COPD. AB - Historical treatments for asthma and COPD have primarily focused on addressing the underlying inflammation and bronchoconstriction that result in air flow obstruction symptoms, including shortness of breath, cough, chest tightness, and mucus production. However, in the past several years, new research into the underlying pathophysiology of asthma and COPD has led to novel targeted therapies that address the underlying pathways that cause these obstructive disorders. As we have gained a better understanding of underlying disease mechanisms, we have begun to use biomarkers and endotypes to personalize our approach to therapy. Targets for asthma and COPD include immunoglobulin E, interleukin 5, interleukin 4/interleukin 13, thymic stromal lymphopoietin, interleukin 17, tyrosine kinases, and others. The new biologics are generally safe and well tolerated, and are bringing promise and hope of personalized therapy to patients with severe asthma. PMID- 29794203 TI - Clinical Pharmacology of Oral Maintenance Therapies for Obstructive Lung Diseases. AB - Although inhaled therapies are typically preferred for the maintenance treatment of obstructive lung diseases, oral drug therapies can also play valuable roles. The most commonly used oral agents are phosphodiesterase inhibitors, theophylline, macrolides, leukotriene modifiers, and mucoactive agents. Advantages of these oral agents include the unique pharmacologic mechanisms of action, the avoidance of the challenges of proper inhalational lung administration, and, in most instances, relative drug cost. For many of these agents, anti-inflammatory or immunomodulatory effects are the predominant pharmacologic mechanism that each provides clinical benefit, with the exception of guaifenesin. In addition, theophylline, leukotriene modifiers, chronic macrolides, phosphodiesterase inhibitors, and N-acetylcysteine have been shown to decrease exacerbations in obstructive lung disease. Fairly rapid bronchodilation occurs with the phosphodiesterase inhibitors, theophylline, and leukotriene modifiers, although less than that achieved with inhaled therapies. The clinical roles of phosphodiesterase inhibitors, specifically roflumilast, and macrolides continues to be defined today, whereas the roles theophylline and leukotriene modifiers have probably been largely delineated. Azithromycin is the principal macrolide used chronically for obstructive lung diseases, especially COPD. Although guaifenesin is used widely, its effectiveness is unclear, whereas N acetylcysteine currently has strong evidence supporting a decreased risk of COPD exacerbations. Mucolytic agents like N-acetylcysteine are used more widely outside the United States in obstructive lung diseases. PMID- 29794204 TI - Anti-Proteases and Alpha-1 Antitrypsin Augmentation Therapy. AB - Alpha-1 antitrypsin deficiency is a genetic disease that first highlighted the importance of protease balance in normal lung homeostasis. Proteases such as neutrophil elastase are important in many pulmonary diseases. However, the first commercially licensed anti-protease therapy was used for emphysema in alpha-1 antitrypsin deficiency. The 4 commercial alpha-1 protease inhibitor preparations in the United States are currently given intravenously to augment the serum and alveolar epithelial lining fluid concentrations of alpha-1 antitrypsin. Since the discovery of alpha-1 antitrypsin deficiency in 1963, many genetic polymorphisms of the SERPINA1 gene have been discovered. Because neutrophilic inflammation is the hallmark of usual COPD, anti-protease therapy also has been explored in this disease. Further trials with different dosing schema, inhaled therapy, and in different disease states are all ongoing. These studies would be facilitated by having COPD outcomes that are independent of measurement of air flow and achievable in smaller populations over a short period of time. PMID- 29794206 TI - Aerosol Delivery Devices for Obstructive Lung Diseases. AB - Drug delivery by inhalation is the principal strategy to treat obstructive lung diseases, which affect about 15% of the population in the United States. Aerosol delivery devices have evolved over more than 60 years from the basic pressurized metered-dose inhaler and nebulizer to numerous types of inhalers and devices, including valved holder chambers, dry powder inhalers, soft mist inhalers, as well as smart inhalers and nebulizers. Although these devices improve a patient's ability to self-administer medication, many problems with optimal delivery still exist. Appropriate selection and repeated patient education can help lessen the problems with these devices. Aerosol science is evolving, with methods of measurement that include radio-scintigraphy and magnetic resonance imaging, to provide a better understanding of aerosol delivery and effects. Understanding the science and clinical application of aerosol drug delivery can substantially aid clinicians in optimizing these therapies for their patients. PMID- 29794207 TI - Oxygen Therapy in COPD. AB - Long-term oxygen therapy (LTOT) at home has been demonstrated to improve survival in patients with COPD and severe resting hypoxemia. Support for LTOT is based on 2 landmark trials published nearly 4 decades ago. These results form the basis for reimbursement and prescription of LTOT to this day. Recent work has demonstrated no outcome benefit of LTOT in stable COPD patients with moderate desaturation at rest or during activity. Oxygen therapy during activity and exercise has been shown to alleviate symptoms and maintain arterial oxygen saturation, but not improve long-term outcomes. Oxygen therapy in COPD has a number of physiologic, functional, and biologic effects, not all of which are completely understood. Oxygen therapy in exacerbations of COPD can be both helpful and harmful. New guidance on the use of oxygen therapy during pre hospital care has been published in the United Kingdom. Technology for LTOT represents a challenge for physicians writing prescriptions, durable medical equipment suppliers, caregivers, and patients. New technology for automated control of LTOT shows promise but is hampered by regulatory processes and cost pressures. Recent changes in government reimbursement for home oxygen therapy also present challenges. This paper will review the current evidence regarding LTOT in COPD and the impact on mortality and functional outcomes as well as reviewing technological challenges. PMID- 29794209 TI - Medication Regimens for Managing Stable Asthma. AB - Guideline-based management of asthma was developed as a means of standardizing asthma therapies and of improving outcomes. The National Asthma Education and Prevention Program and the Global Initiative for Asthma guidelines provide recommendations to care providers about the routine management of asthma. There has been rapid development of new therapies for asthma, specifically with the advent of new drug delivery devices and biologic therapies for severe asthma. We are increasingly recognizing that asthma is a heterogenous disease with a diverse underlying pathophysiology, and therefore, it is imperative for care providers to begin to understand asthma phenotypes and endotypes, and the implications of these classifications on management, especially of severe refractory asthma. This article serves as a review of guideline-based therapy for asthma and includes updates on alternative therapies, new approaches that use previously recognized therapies, and special populations with asthma. PMID- 29794208 TI - An Update on the Global Initiative for Chronic Obstructive Lung Disease 2017 Guidelines With a Focus on Classification and Management of Stable COPD. AB - The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines offer important changes to the assessment and management of stable COPD of importance to practitioners, respiratory therapists, pharmacists, and nurses who care for patients with COPD. Therapies are now chosen based on the burden of symptoms and the history of COPD exacerbations, and inhaler regimens are modifiable based on continual clinical reassessment. Although identifying the degree of airway obstruction remains important for informing the clinical status of the patient with COPD, FEV1 is no longer used to direct the therapeutic approach. Therapies and modes of inhaled medication delivery for each GOLD grouping have been modified and reflect the need for reevaluation of patient symptoms and COPD exacerbation history as an indicator to add or withdraw therapies. As the knowledge of this important disease continues to expand, exacerbation and symptom prevention in patients with stable COPD will remain as an important target of COPD therapies and research. Novel drug combinations and delivery devices are sure to positively affect the practitioner's approach to patients with stable COPD. The new 2017 GOLD guidelines represent a step toward personalized care of the patient with COPD. PMID- 29794210 TI - Medication Regimens for Managing COPD Exacerbations. AB - Exacerbations are a hallmark feature of COPD and contribute to morbidity and mortality. There is general agreement that the pharmacotherapy of COPD exacerbations includes bronchodilators, corticosteroids, and antibiotics. Strong evidence exists for the benefit of corticosteroids for exacerbations and of antibiotics in the acute hospital setting. There remains considerable uncertainty, however, in the best drug selection, dose, route, and duration of treatment. This article reviews the evidence base and expert recommendations for drug treatment of COPD exacerbations in the out-patient and in-patient settings. PMID- 29794211 TI - Medication Regimens for Managing Acute Asthma. AB - Asthma exacerbation is defined as a progressive increase in symptoms of shortness of breath, cough, or wheezing sufficient to require a change in therapy. After ruling out diagnoses that mimic an asthma exacerbation, therapy should be initiated. Short-acting beta2 agonists and short-acting muscarinic antagonists are effective as bronchodilators for asthma in the acute setting. Systemic corticosteroids to reduce airway inflammation continue to be the mainstay therapy for asthma exacerbations, and, unless there is a contraindication, the oral route is favored. Based on the current evidence, nebulized magnesium should not be routinely used in acute asthma. The evidence favors the use of intravenous magnesium sulfate in selected cases, particularly in severe exacerbations. Methylxanthines have a minimum role as therapy for asthma exacerbations but may be considered in refractory cases of status asthmaticus with careful monitoring of toxicity. Current guidelines recommend the use of helium-oxygen mixtures in patients who do not respond to standard therapies or those with severe disease. PMID- 29794212 TI - Drug Development for Asthma and COPD: A Regulatory Perspective. AB - This review addresses drug development intended to support United States clearance for asthma and COPD by explaining basic regulatory terms and broadly discussing the regulatory pathways to clearance. Some of the key clinical regulatory challenges that are faced by drugs for asthma and COPD are explained and clarified, both overall and by class of drug, citing relevant examples that emphasize key lessons. Generic drug development of inhaled drugs is also addressed. The purpose of this review is to provide the reader with a greater understanding and appreciation of asthma and COPD drug development from the regulatory perspective. PMID- 29794214 TI - Editor's Commentary. PMID- 29794213 TI - Adherence in Asthma and COPD: New Strategies for an Old Problem. AB - Adherence broadly encompasses the decisions patients make as to whether health care advice should be initiated, as well as the degree to which the recommended health behaviors, once started, are maintained. Disease-related conditions such as severity and duration of illness, as well as treatment-related features such as frequency of dosing and side effects, are 2 of several factors that influence adherence. Other factors affecting adherence include socioeconomic status, patient-related causes, and health system-related reasons. Adherence is rarely, if ever, an all-or-none phenomenon. Typically, patients follow some recommendations closely while deciding others are optional; these decisions are often made without consulting with or notifying health care professionals. Non adherence can be categorized as either unintentional or intentional. Unintentional non-adherence is easier to remedy because it responds to patient education, simplification of treatment regimens, or the use of a reminder system. Intentional non-adherence is more complex and challenging to address because patients exhibiting these behaviors often do not find evidence-based recommendations compelling, lack the motivation to follow advice, or have deeply entrenched personal beliefs that conflict with health guidance. Novel psychotherapeutic behavioral interventions, such as shared decision-making, motivational interviewing, and coaching are some approaches being tested to determine their effectiveness in mitigating the resistance to treatment that characterizes intentional non-adherence in asthma and COPD populations. In this narrative review, the extent of non-adherence to asthma and COPD management recommendations is explored, the factors affecting adherence are explicated, the methods used to measure adherence are compared and contrasted, and the effectiveness of strategies targeting unintentional and intentional non-adherence is detailed. PMID- 29794215 TI - What makes clinical labour different? The case of human guinea pigging. AB - Each year thousands of individuals enrol in clinical trials as healthy volunteers to earn money. Some of them pursue research participation as a full-time or at least a part-time job. They call themselves professional or semiprofessional guinea pigs. The practice of paying healthy volunteers raises numerous ethical concerns. Different payment models have been discussed in literature. Dickert and Grady argue for a wage-payment model. This model gives research subjects a standardised hourly wage, and it is based on an assumption that research participation is morally indistinguishable from other forms of unskilled labour. In this paper, I will challenge this assumption. I will argue that human guinea pigging has particular characteristics which taken together make it significantly different from other forms of labour. (1) Participation in research is skill independent. Healthy volunteers are valuable not because they are skilful persons, but because they are human bodies. (2) The role of research volunteers is mainly passive. They are not asked to produce goods or deliver services. They are paid for enduring unpleasant, painful and risky interventions performed by investigators. (3) Research volunteering involves inherent risks and uncertainties, and subjects have little or no control over their minimisation and materialisation. I conclude that participation in clinical research is a specific kind of activity. It is more like renting out one's body to strangers, than working. Thus, research participation should not be treated on par with other forms of employment. PMID- 29794216 TI - Postimpact earliest Paleogene warming shown by fish debris oxygen isotopes (El Kef, Tunisia). AB - Greenhouse warming is a predicted consequence of the Chicxulub impact, but supporting data are sparse. This shortcoming compromises understanding of the impact's effects, and it has persisted due to an absence of sections that both contain suitable material for traditional carbonate- or organic-based paleothermometry and are complete and expanded enough to resolve changes on short time scales. We address the problem by analyzing the oxygen isotopic composition of fish debris, phosphatic microfossils that are relatively resistant to diagenetic alteration, from the Global Stratotype Section and Point for the Cretaceous/Paleogene boundary at El Kef, Tunisia. We report an ~1 per mil decrease in oxygen isotopic values (~5 degrees C warming) beginning at the boundary and spanning ~300 centimeters of section (~100,000 years). The pattern found matches expectations for impact-initiated greenhouse warming. PMID- 29794217 TI - Atmospheric blocking as a traffic jam in the jet stream. AB - Atmospheric blocking due to anomalous, persistent meandering of the jet stream often causes weather extremes in the mid-latitudes. Despite the ubiquity of blocking, the onset mechanism is not well understood. Here we demonstrate a close analogy between blocking and traffic congestion on a highway by using meteorological data and show that blocking and traffic congestion can be described by a common mathematical theory. The theory predicts that the jet stream has a capacity for the flux of wave activity (a measure of meandering), just as the highway has traffic capacity, and when the capacity is exceeded, blocking manifests as congestion. Stationary waves modulate the jet stream's capacity for transient waves and localize block formation. Climate change likely affects blocking frequency by modifying the jet stream's proximity to capacity. PMID- 29794218 TI - Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS. AB - Understanding the practical limitations of chemical reactions is critically important for efficiently planning the synthesis of compounds in pharmaceutical, agrochemical, and specialty chemical research and development. However, literature reports of the scope of new reactions are often cursory and biased toward successful results, severely limiting the ability to predict reaction outcomes for untested substrates. We herein illustrate strategies for carrying out large-scale surveys of chemical reactivity by using a material-sparing nanomole-scale automated synthesis platform with greatly expanded synthetic scope combined with ultrahigh-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PMID- 29794219 TI - Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation. AB - The precatalytic spliceosome (B complex) is preceded by the pre-B complex. Here we report the cryo-electron microscopy structures of the Saccharomyces cerevisiae pre-B and B complexes at average resolutions of 3.3 to 4.6 and 3.9 angstroms, respectively. In the pre-B complex, the duplex between the 5' splice site (5'SS) and U1 small nuclear RNA (snRNA) is recognized by Yhc1, Luc7, and the Sm ring. In the B complex, U1 small nuclear ribonucleoprotein is dissociated, the 5'-exon 5'SS sequences are translocated near U6 snRNA, and three B-specific proteins may orient the precursor messenger RNA. In both complexes, U6 snRNA is anchored to loop I of U5 snRNA, and the duplex between the branch point sequence and U2 snRNA is recognized by the SF3b complex. Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome. PMID- 29794222 TI - Maturation of polycistronic mRNAs by the endoribonuclease RNase Y and its associated Y-complex in Bacillus subtilis. AB - Endonucleolytic cleavage within polycistronic mRNAs can lead to differential stability, and thus discordant abundance, among cotranscribed genes. RNase Y, the major endonuclease for mRNA decay in Bacillus subtilis, was originally identified for its cleavage activity toward the cggR-gapA operon, an event that differentiates the synthesis of a glycolytic enzyme from its transcriptional regulator. A three-protein Y-complex (YlbF, YmcA, and YaaT) was recently identified as also being required for this cleavage in vivo, raising the possibility that it is an accessory factor acting to regulate RNase Y. However, whether the Y-complex is broadly required for RNase Y activity is unknown. Here, we used end-enrichment RNA sequencing (Rend-seq) to globally identify operon mRNAs that undergo maturation posttranscriptionally by RNase Y and the Y-complex. We found that the Y-complex is required for the majority of RNase Y-mediated mRNA maturation events and also affects riboswitch abundance in B. subtilis In contrast, noncoding RNA maturation by RNase Y often does not require the Y complex. Furthermore, deletion of RNase Y has more pleiotropic effects on the transcriptome and cell growth than deletions of the Y-complex. We propose that the Y-complex is a specificity factor for RNase Y, with evidence that its role is conserved in Staphylococcus aureus. PMID- 29794223 TI - Astronomical metronome of geological consequence. PMID- 29794220 TI - Phylogenomics reveals multiple losses of nitrogen-fixing root nodule symbiosis. AB - The root nodule symbiosis of plants with nitrogen-fixing bacteria affects global nitrogen cycles and food production but is restricted to a subset of genera within a single clade of flowering plants. To explore the genetic basis for this scattered occurrence, we sequenced the genomes of 10 plant species covering the diversity of nodule morphotypes, bacterial symbionts, and infection strategies. In a genome-wide comparative analysis of a total of 37 plant species, we discovered signatures of multiple independent loss-of-function events in the indispensable symbiotic regulator NODULE INCEPTION in 10 of 13 genomes of nonnodulating species within this clade. The discovery that multiple independent losses shaped the present-day distribution of nitrogen-fixing root nodule symbiosis in plants reveals a phylogenetically wider distribution in evolutionary history and a so-far-underestimated selection pressure against this symbiosis. PMID- 29794221 TI - Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes. AB - Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1-/- adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy. PMID- 29794224 TI - One-Stop-Shop Whole-Body 68Ga-PSMA-11 PET/MRI Compared with Clinical Nomograms for Preoperative T and N Staging of High-Risk Prostate Cancer. AB - Our aim was to assess the diagnostic potential of 1-stop-shop prostate-specific membrane antigen ligand (68Ga-PSMA-11) PET/MRI compared with preoperative staging nomograms in patients with high-risk prostate cancer. Methods: A total of 102 patients underwent 68Ga-PSMA-11 PET/MRI before intended radical prostatectomy with lymph node dissection. Preoperative variables determined the probabilities for lymph node metastases (LNM), extracapsular extension (ECE), and seminal vesical involvement (SVI) using the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram and Partin tables. Receiver-operating-characteristic analyses were performed to determine best discriminatory cutoffs. On a cohort basis, positivity rates of imaging and nomograms were compared with pathologic prevalence. On a patient basis, sensitivity, specificity, and area under the curves were calculated. Finally, the full concordance of each method to postoperative T and N stage was determined. Results: Seventy-three patients were finally analyzed. On a cohort basis, the MSKCC nomogram (39.7%) positivity rate was most concordant with pathologic prevalence for LNM (34.3%) compared with Partin tables (14.1%) and imaging (20.6%). Prevalence of ECE (72.6%) was best predicted by MSKCC nomograms and imaging (83.6% each), compared with Partin tables (38.4%). For prevalence of SVI (45.2%), imaging (47.9%) performed superior to MSKCC (37.6%) and Partin tables (19.3%). On a patient basis, AUCs for LNM, ECE, and SVI did not differ significantly between tests (P > 0.05). Imaging revealed a high specificity (100%) for LNM and a sensitivity (60%) comparable to the MSKCC nomogram (68%) and Partin tables (60%). For ECE, imaging revealed the highest sensitivity (94.3%) compared with the MSKCC nomogram (66%) and Partin tables (71.1%). For SVI, sensitivity and specificity of imaging and the MSKCC nomogram were comparable (81.5% and 80% vs. 87.9% and 75%). The rate of concordance to the final pTN stage was 60.3% for imaging, 52.1% for the MSKCC nomogram, and 39.7% for Partin tables. Conclusion: In our analysis, preoperative 1-stop-shop 68Ga-PSMA-11 PET/MRI performs at least equally for T and N stage prediction compared with nomograms in high-risk prostate cancer patients. Despite an improved prediction of the full final stage and the yield of additional anatomic information, the use of 68Ga-PSMA-11 PET/MRI warrants further prospective evaluation. PMID- 29794225 TI - Depicting Changes in Tumor Biology in Response to Cetuximab Monotherapy or Combination Therapy by Apoptosis and Proliferation Imaging Using 18F-ICMT-11 and 18F-FLT PET. AB - Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7-specific isatin-5-sulfonamide 18F-ICMT-11 (18F-(S)-1-((1 (2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluoro-phenoxymethyl) pyrrolidine-1-sulfonyl)isatin) and 18F-FLT (3'-deoxy-3'-18F-fluorothymidine), were used to detect early treatment-induced changes in tumor biology and determine whether any of these changes indicate a response to cetuximab, administered as monotherapy or combination therapy with gemcitabine. Methods: In mice bearing cetuximab-sensitive H1975 tumors (non-small lung cancer), the effects of single or repeated doses of the antiepidermal growth factor receptor antibody cetuximab (10 mg/kg on day 1 only or on days 1 and 2) or a single dose of gemcitabine (125 mg/kg on day 2) were investigated by 18F-ICMT-11 or 18F-FLT on day 3. Imaging was also performed after 2 doses of cetuximab (days 1 and 2) in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer). For imaging histology comparison, tumors were evaluated for proliferation (Ki-67 and thymidine kinase 1 [TK1]), cell death (cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling [TUNEL]), and target engagement (epidermal growth factor receptor expression) by immunohistochemistry, immunofluorescence, and immunoblotting, respectively. Tumor and plasma were analyzed for thymidine and gemcitabine metabolites by liquid chromatography-mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab (75%) and combination treatment (46%). Although a single dose of cetuximab was insufficient to induce apoptosis, it did affect proliferation. Significant reductions in tumor 18F-FLT uptake (44%-50%; P < 0.001) induced by cetuximab monotherapy and combination therapy were paralleled by a clear decrease in proliferation (Ki-67 decrease, 72%-95%; P < 0.0001), followed by a marked tumor growth delay. TK1 expression and tumor thymidine concentrations were profoundly reduced. Neither imaging tracer depicted the gemcitabine-induced tumor changes. However, cleaved caspase-3 and Ki-67 staining did not significantly differ after gemcitabine treatment whereas TK1 expression and thymidine concentrations increased. No cetuximab-induced modulation of the imaging tracers or other response markers was detected in the insensitive model of HCT116. Conclusion: 18F-ICMT-11 and 18F-FLT are valuable tools to assess cetuximab sensitivity depicting distinct and time-variant aspects of treatment response. PMID- 29794228 TI - Sixty seconds on . . . eggs. PMID- 29794229 TI - Epidemiology and Risk Factors of Infection in Early Childhood. AB - BACKGROUND: There is a large, unexplained variation in the frequency of childhood infections. We described incidence and risk factors of infections in early childhood. METHODS: Simple infections were captured during the first 3 years of life in the Copenhagen Prospective Studies on Asthma in Childhood 2000 birth cohort. Environmental exposures were analyzed by quasi-Poisson regression and sparse principal component analysis. RESULTS: The 334 children experienced a median of 14 (range 2-43) infectious episodes at ages 0 to 3 years. The overall rate of infections was associated with the number of children in the day care (adjusted incidence rate ratio [aIRR] 1.09 [1.2-1.16]) and the m2 per child in the day care (aIRR 0.96 [0.92-0.99]). Upper respiratory infections were also associated with the number of children in the day care (aIRR 1.11 [1.03-1.20]) and the m2 per child in the day care (aIRR 0.95 [0.91-0.99]), whereas lower respiratory infections were associated with caesarean section (aIRR 1.49 [1.12 1.99]), maternal smoking (aIRR 1.66 [1.18-2.33]), older siblings (aIRR 1.54 [1.19 2.01]), and the age at entry to day care (aIRR 0.77 [0.65-0.91]). The sparse principal component analysis revealed a risk factor profile driven by tobacco exposure, social circumstances, and domestic pets, but could only be used to explain 8.4% of the infection burden. CONCLUSIONS: Children experienced around 14 infections during the first 3 years of life, but incidences varied greatly. Environmental exposures only explained a small fraction of the variation, suggesting host factors as major determinants of infectious burden. PMID- 29794227 TI - Longitudinal Characterization of mGluR5 Using 11C-ABP688 PET Imaging in the Q175 Mouse Model of Huntington Disease. AB - Metabotropic glutamate receptor 5 (mGluR5) represents a potential therapeutic target for Huntington disease. Using 11C-ABP688 (3-(6-methyl-pyridin-2-ylethynyl) cyclohex-2-enone-O-11C-methyl-oxime), a noncompetitive and highly selective antagonist for mGluR5, we aimed to longitudinally characterize in vivo changes in mGluR5 by means of PET imaging in the Q175 mouse model of Huntington disease. Methods: 11C-ABP688 PET imaging, followed by a CT scan, was performed on 18 heterozygous mice and 18 wild-type (WT) littermates at 3 different time points (6, 9, and 13 mo old). 11C-ABP688 nondisplaceable binding potential (BPND) was calculated for each time point in striatum and cortex using the cerebellum as the reference region. In addition, voxel-based statistical parametric mapping (SPM) analysis was performed on BPND images. Postmortem validation of mGluR5 level and neuronal density was performed on the mice at 6 mo old. Results: The 11C-ABP688 BPND of heterozygous animals was significantly reduced at all time points in the striatum (-13.1%, -13.5%, and -14.2% at 6, 9, and 13 mo, respectively; P < 0.001 for all) and in the cortex (-9.8%, -10.2%, and -10.6%, respectively; P < 0.01 for all), when compared with WT animals. Longitudinal changes in 11C-ABP688 BPND were also found in heterozygous mice, showing a reduction at 13 mo compared with 6 mo (-10.4%, P < 0.05). SPM analysis confirmed reduced BPND in heterozygous compared with WT mice, as well as a time-related decline in 11C-ABP688 binding in the striatum of heterozygous mice. Postmortem analysis confirmed a mGluR5 decrease in both striatum (-36.6%; P < 0.01) and cortex (-16.6%; P < 0.05) in heterozygous mice, whereas no difference in neuronal density was found. Conclusion: In vivo imaging of mGluR5 using 11C-ABP688 PET/CT revealed a marked reduction in ligand binding in the striatum and cortex of heterozygous mice, compared with WT mice, as well as a temporal decline. This study suggests that 11C-ABP688 PET imaging is a potential biomarker to monitor the progression of, and therapeutic strategies for, Huntington disease. PMID- 29794230 TI - Predictors of Medication Continuity in Children With ADHD. AB - OBJECTIVES: To identify predictors of attention-deficit/hyperactivity disorder (ADHD) medication continuity, hypothesizing greater continuity among children with (1) greater child acceptance of treatment, (2) parent belief in longer time course for ADHD, (3) positive differential between parent-perceived need for and concerns about medication, and (4) greater parent-perceived alliance with their child's doctor. METHODS: We conducted a prospective longitudinal cohort of 89 children aged 6 to 10 years old newly treated for ADHD by 1 of 44 pediatricians in 11 practices. Parents completed validated surveys on their beliefs about ADHD and medicine. We audited charts and obtained pharmacy dispensing records. In our analyses, we examined the relationship between predictor variables (eg, sociodemographic and clinical characteristics, quality of care, and belief measures) and short-term (first 90 days after starting medication) and long-term (91-450 days) medication continuity as defined by the number of days covered with medication. RESULTS: Children had a median of 81% of days covered over 0 to 90 days and 54% of days covered over 91 to 450 days after starting medicine. In the first 90 days, medication coverage related to child age, satisfaction with information about medicine, medication titration, symptom reduction, parent beliefs about control over symptoms, uncertainty about treating with medicine, and working alliance. Long-term medication continuity related to child acceptance of treatment and differential between parent-perceived need for and concerns about medication at 3 months, not baseline factors. CONCLUSIONS: Adherence is a process that can change over time in response to experiences with treatment. Interventions are needed to promote productive interactions between pediatricians and families in support of continuity. PMID- 29794226 TI - The Immunoimaging Toolbox. AB - The recent clinical success of cancer immunotherapy has renewed interest in the development of tools to image the immune system. In general, immunotherapies attempt to enable the body's own immune cells to seek out and destroy malignant disease. Molecular imaging of the cells and molecules that regulate immunity could provide unique insight into the mechanisms of action, and failure, of immunotherapies. In this article, we will provide a comprehensive overview of the current state-of-the-art immunoimaging toolbox with a focus on imaging strategies and their applications toward immunotherapy. PMID- 29794231 TI - STK25 regulates oxidative capacity and metabolic efficiency in adipose tissue. AB - Whole-body energy homeostasis at over-nutrition critically depends on how well adipose tissue remodels in response to excess calories. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of ectopic lipid storage in non-adipose tissue and systemic insulin resistance in the context of nutritional stress. Here, we investigated the role of STK25 in regulation of adipose tissue dysfunction in mice challenged with a high-fat diet. We found that overexpression of STK25 in high-fat-fed mice resulted in impaired mitochondrial function and aggravated hypertrophy, inflammatory infiltration and fibrosis in adipose depots. Reciprocally, Stk25-knockout mice displayed improved mitochondrial function and were protected against diet-induced excessive fat storage, meta-inflammation and fibrosis in brown and white adipose tissues. Furthermore, in rodent HIB-1B cell line, STK25 depletion resulted in enhanced mitochondrial activity and consequently, reduced lipid droplet size, demonstrating an autonomous action for STK25 within adipocytes. In summary, we provide the first evidence for a key function of STK25 in controlling the metabolic balance of lipid utilization vs lipid storage in brown and white adipose depots, suggesting that repression of STK25 activity offers a potential strategy for establishing healthier adipose tissue in the context of chronic exposure to dietary lipids. PMID- 29794232 TI - Association between tax structure and cigarette consumption: findings from the International Tobacco Control Policy Evaluation (ITC) Project. AB - BACKGROUND: Recent studies show that greater price variability and more opportunities for tax avoidance are associated with tax structures that depart from a specific uniform one. These findings indicate that tax structures other than a specific uniform one may lead to more cigarette consumption. OBJECTIVE: This paper aims to examine how cigarette tax structure is associated with cigarette consumption. METHODS: We used survey data taken from the International Tobacco Control Policy Evaluation Project in 17 countries to conduct the analysis. Self-reported cigarette consumption was aggregated to average measures for each surveyed country and wave. The effect of tax structures on cigarette consumption was estimated using generalised estimating equations after adjusting for sociodemographic characteristics, average taxes and year fixed effects. FINDINGS: Our study provides important empirical evidence of a relationship between tax structure and cigarette consumption. We find that a change from a specific to an ad valorem structure is associated with a 6%-11% higher cigarette consumption. In addition, a change from uniform to tiered structure is associated with a 34%-65% higher cigarette consumption. The results are consistent with existing evidence and suggest that a uniform and specific tax structure is the most effective tax structure for reducing tobacco consumption. PMID- 29794233 TI - MSVAT-SPACE-STIR and SEMAC-STIR for Reduction of Metallic Artifacts in 3T Head and Neck MRI. AB - BACKGROUND AND PURPOSE: The incidence of metallic dental restorations and implants is increasing, and head and neck MR imaging is becoming challenging regarding artifacts. Our aim was to evaluate whether multiple-slab acquisition with view angle tilting gradient based on a sampling perfection with application optimized contrasts by using different flip angle evolution (MSVAT-SPACE)-STIR and slice-encoding for metal artifact correction (SEMAC)-STIR are beneficial regarding artifact suppression compared with the SPACE-STIR and TSE-STIR in vitro and in vivo. MATERIALS AND METHODS: At 3T, 3D artifacts of 2 dental implants, supporting different single crowns, were evaluated. Image quality was evaluated quantitatively (normalized signal-to-noise ratio) and qualitatively (2 reads by 2 blinded radiologists). Feasibility was tested in vivo in 5 volunteers and 5 patients, respectively. RESULTS: Maximum achievable resolution and the normalized signal-to-noise ratio of MSVAT-SPACE-STIR were higher compared with SEMAC-STIR. Performance in terms of artifact correction was dependent on the material composition. For highly paramagnetic materials, SEMAC-STIR was superior to MSVAT SPACE-STIR (27.8% smaller artifact volume) and TSE-STIR (93.2% less slice distortion). However, MSVAT-SPACE-STIR reduced the artifact size compared with SPACE-STIR by 71.5%. For low-paramagnetic materials, MSVAT-SPACE-STIR performed as well as SEMAC-STIR. Furthermore, MSVAT-SPACE-STIR decreased artifact volume by 69.5% compared with SPACE-STIR. The image quality of all sequences did not differ systematically. In vivo results were comparable with in vitro results. CONCLUSIONS: Regarding susceptibility artifacts and acquisition time, MSVAT-SPACE STIR might be advantageous over SPACE-STIR for high-resolution and isotropic head and neck imaging. Only for materials with high-susceptibility differences to soft tissue, the use of SEMAC-STIR might be beneficial. Within limited acquisition times, SEMAC-STIR cannot exploit its full advantage over TSE-STIR regarding artifact suppression. PMID- 29794234 TI - Hematocrit Measurement with R2* and Quantitative Susceptibility Mapping in Postmortem Brain. AB - BACKGROUND AND PURPOSE: Noninvasive venous oxygenation quantification with MR imaging will improve the neurophysiologic investigation and the understanding of the pathophysiology in neurologic diseases. Available MR imaging methods are limited by sensitivity to flow and often require assumptions of the hematocrit level. In situ postmortem imaging enables evaluation of methods in a fully deoxygenated environment without flow artifacts, allowing direct calculation of hematocrit. This study compares 2 venous oxygenation quantification methods in in situ postmortem subjects. MATERIALS AND METHODS: Transverse relaxation (R2*) mapping and quantitative susceptibility mapping were performed on a whole-body 4.7T MR imaging system. Intravenous measurements in major draining intracranial veins were compared between the 2 methods in 3 postmortem subjects. The quantitative susceptibility mapping technique was also applied in 10 healthy control subjects and compared with reference venous oxygenation values. RESULTS: In 2 early postmortem subjects, R2* mapping and quantitative susceptibility mapping measurements within intracranial veins had a significant and strong correlation (R2 = 0.805, P = .004 and R2 = 0.836, P = .02). Higher R2* and susceptibility values were consistently demonstrated within gravitationally dependent venous segments during the early postmortem period. Hematocrit ranged from 0.102 to 0.580 in postmortem subjects, with R2* and susceptibility as large as 291 seconds-1 and 1.75 ppm, respectively. CONCLUSIONS: Measurements of R2* and quantitative susceptibility mapping within large intracranial draining veins have a high correlation in early postmortem subjects. This study supports the use of quantitative susceptibility mapping for evaluation of in vivo venous oxygenation and postmortem hematocrit concentrations. PMID- 29794235 TI - Prevalence of Cerebral Microhemorrhage following Chronic Blast-Related Mild Traumatic Brain Injury in Military Service Members Using Susceptibility-Weighted MRI. AB - BACKGROUND AND PURPOSE: Cerebral microhemorrhages are a known marker of mild traumatic brain injury. Blast-related mild traumatic brain injury relates to a propagating pressure wave, and there is evidence that the mechanism of injury in blast-related mild traumatic brain injury may be different from that in blunt head trauma. Two recent reports in mixed cohorts of blunt and blast-related traumatic brain injury in military personnel suggest that the prevalence of cerebral microhemorrhages is lower than in civilian head injury. In this study, we aimed to characterize the prevalence of cerebral microhemorrhages in military service members specifically with chronic blast-related mild traumatic brain injury. MATERIALS AND METHODS: Participants were prospectively recruited and underwent 3T MR imaging. Susceptibility-weighted images were assessed by 2 neuroradiologists independently for the presence of cerebral microhemorrhages. RESULTS: Our cohort included 146 veterans (132 men) who experienced remote blast related mild traumatic brain injury (mean, 9.4 years; median, 9 years after injury). Twenty-one (14.4%) reported loss of consciousness for <30 minutes. Seventy-seven subjects (52.7%) had 1 episode of blast-related mild traumatic brain injury; 41 (28.1%) had 2 episodes; and 28 (19.2%) had >2 episodes. No cerebral microhemorrhages were identified in any subject, as opposed to the frequency of SWI-detectable cerebral microhemorrhages following blunt-related mild traumatic brain injury in the civilian population, which has been reported to be as high as 28% in the acute and subacute stages. CONCLUSIONS: Our results may reflect differences in pathophysiology and the mechanism of injury between blast- and blunt-related mild traumatic brain injury. Additionally, the chronicity of injury may play a role in the detection of cerebral microhemorrhages. PMID- 29794237 TI - Abnormal Blood Oxygen Level-Dependent Fluctuations in Focal Cortical Dysplasia and the Perilesional Zone: Initial Findings. AB - BACKGROUND AND PURPOSE: Focal cortical dysplasia is a common cause of intractable epilepsy for which neurosurgery is an option. Delineations of a focal cortical dysplasia lesion on structural brain images may not necessarily reflect the functional borders of normal tissue. Our objective was to determine whether abnormalities in spontaneous blood oxygen level-dependent fluctuations arise in focal cortical dysplasia lesions and proximal regions. MATERIALS AND METHODS: Fourteen patients with focal cortical dysplasia-related epilepsy and 16 healthy controls underwent structural and resting-state functional MR imaging. Three known blood oxygen level-dependent measures were determined, including the fractional amplitude of low-frequency fluctuations, regional homogeneity, and wavelet entropy. These measures were evaluated in the lesion and perilesional zone and normalized to the contralateral cortex of patients with focal cortical dysplasia and healthy controls. RESULTS: Patients showed significantly decreased fractional amplitude of low-frequency fluctuations and increased wavelet entropy in the focal cortical dysplasia lesion and the perilesional zone (<=2 cm) relative to the contralateral homotopic cortex and the same regions in healthy controls. Regional homogeneity was significantly increased in the focal cortical dysplasia lesion compared with the contralateral homotopic cortex and healthy controls. CONCLUSIONS: Abnormalities in spontaneous blood oxygen level-dependent fluctuations were seen up to 2 cm distant from the radiologically visible boundary. It was demonstrated that functional boundaries go beyond structural boundaries of focal cortical dysplasia lesions. Validation is required to reveal whether this information is valuable for surgical planning and outcome evaluation of focal cortical dysplasia lesions and comparing current results with electrophysiologic analysis. PMID- 29794236 TI - Clinical Significance of Intraplaque Hemorrhage in Low- and High-Grade Basilar Artery Stenosis on High-Resolution MRI. AB - BACKGROUND AND PURPOSE: Intraplaque hemorrhage within intracranial atherosclerotic plaques identified by high-resolution MR imaging has been studied as a potential marker of stroke risk. However, previous studies only examined intracranial arteries with high-grade stenosis (degree of stenosis, >50%). This study aimed to ascertain the clinical relevance of intraplaque hemorrhage in patients with low- and high-grade stenotic basilar artery plaques. MATERIALS AND METHODS: Patients with basilar artery stenosis (n = 126; mean age, 62 +/- 10 years; 66 symptomatic and 60 asymptomatic) underwent high-resolution MR imaging. The relationship between imaging findings (intraplaque hemorrhage, contrast enhancement, degree of stenosis, minimal lumen area, and plaque burden) and symptoms was analyzed. RESULTS: Intraplaque hemorrhage was identified in 22 patients (17.5%), including 21 (31.8%) symptomatic patients and 1 (1.7%) asymptomatic patient. Multivariate analysis showed that intraplaque hemorrhage was the strongest independent marker of symptomatic status (odds ratio, 27.5; 95% CI, 3.4-221.5; P = .002). Contrast enhancement was also independently associated with symptomatic status (odds ratio, 9.9; 95% CI, 1.5-23.6; P = .016). Stenosis, minimal lumen area, and plaque burden were not correlated with symptoms (P > .05). Intraplaque hemorrhage was present in both low- and high-grade stenotic basilar arteries (11.3% versus 16.3%, P = .63). Diagnostic performance values of intraplaque hemorrhage for patients with acute/subacute symptomatic stroke were the following: specificity, 98.3%; sensitivity, 31.8%; positive predictive value, 95.5%; and negative predictive value, 56.7%. CONCLUSIONS: Intraplaque hemorrhage is present in both low- and high-grade stenotic basilar artery plaques and is independently associated with symptomatic stroke status. Intraplaque hemorrhage may identify high-risk plaque and provide new insight into the management of patient with stroke without significant stenosis. PMID- 29794238 TI - Efficacy and Safety of Percutaneous Microwave Ablation and Cementoplasty in the Treatment of Painful Spinal Metastases and Myeloma. AB - BACKGROUND AND PURPOSE: Painful spinal metastases are a common cause of cancer related morbidity. Percutaneous ablation presents an attractive minimally invasive alternative to conventional therapies. We performed a retrospective review of 69 patients with 102 painful spinal metastases undergoing microwave ablation and cementoplasty to determine the efficacy and safety of this treatment. MATERIALS AND METHODS: Procedures were performed between January 2015 and October 2016 with the patient under general anesthesia using image guidance for 102 spinal metastases in 69 patients in the following areas: cervical (n = 2), thoracic (n = 50), lumbar (n = 34), and sacral (n = 16) spine. Tumor pathologies included the following: multiple myeloma (n = 10), breast (n = 27), lung (n = 12), thyroid (n = 6), prostate (n = 5), colon (n = 4), renal cell (n = 3), oral squamous cell (n = 1), and adenocarcinoma of unknown origin (n = 1). Procedural efficacy was determined using the visual analog scale measured preprocedurally and at 2-4 weeks and 20-24 weeks postprocedure. Tumor locoregional control was assessed on follow-up cross-sectional imaging. Procedural complications were recorded to establish the safety profile. RESULTS: The median ablation time was 4 minutes 30 seconds +/- 7 seconds, and energy dose, 4.1 +/- 1.6 kJ. Median visual analog scale scores were the following: 7.0 +/- 1.8 preprocedurally, 2 +/- 1.6 at 2-4 weeks, and 2 +/- 2.1 at 20-24 weeks. Eight patients died within 6 months following the procedure. Follow-up imaging in the surviving patients at 20-24 weeks demonstrated no locoregional progression in 59/61 patients. Two complications were documented (S1 nerve thermal injury and skin burn). CONCLUSIONS: Microwave ablation is an effective and safe treatment technique for painful spinal metastases. Further studies may be helpful in determining the role of microwave ablation in locoregional control of metastases. PMID- 29794243 TI - Mind the gap: missed valve disease diagnosis. PMID- 29794242 TI - Prevalence of human papillomavirus by geographical regions, sexual orientation and HIV status in China: a systematic review and meta-analysis. AB - OBJECTIVE: Human papillomavirus (HPV) infection causes multiple cancers in both women and men. In China, both HPV vaccination and cervical cancer screening coverages are low. We aim to investigate the temporal and geographical trends of HPV DNA prevalence in heterosexual men, women, men who have sex with men (MSM) and people living with HIV (PLHIV) in China. METHODS: We conducted a systematic review, collecting publications in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Data from January 2000 to May 2017. A total of 247 studies were selected for this meta-analysis to estimate pooled HPV prevalence, incidence of cervical cancer and risk of infection for subgroups. Meta-regression was applied to identify contributing factors to prevalence heterogeneities. RESULTS: The national HPV prevalence was 15.6% (95% CI (14.4% to 16.9%)) in women with normal cervical cytology, and Central China had the highest prevalence (20.5% (15.2% to 25.8%)). HPV prevalence in heterosexual men (14.5% (11.3% to 17.7%)) was comparable with that of women (OR=1.09 (0.98 to 1.17)), but HPV prevalence in MSM (59.9% (52.2% to 67.6%)) was significantly higher than that in heterosexual men (OR=8.81 (8.01 to 9.69)). HIV-positive women (45.0% (38.4% to 51.6%)) and HIV-positive MSM (87.5% (82.3% to 90.9%)) had 4.67 (3.61 to 6.03) and 6.46 (5.20 to 8.02) times higher risk of HPV infection than their HIV negative counterparts. CONCLUSION: HPV infection is prevalent in China, particularly in Central China, in comparison with the global level and neighbouring countries. Targeted HPV vaccination for women, MSM and PLHIV and scale-up of cervical screening for women are priorities in curbing the HPV epidemic in China. PMID- 29794241 TI - Perivascular Adipose Tissue-Derived PDGF-D Contributes to Aortic Aneurysm Formation During Obesity. AB - Obesity increases the risk of vascular diseases, including aortic aneurysm (AA). Perivascular adipose tissue (PVAT) surrounding arteries are altered during obesity. However, the underlying mechanism of adipose tissue, especially PVAT, in the pathogenesis of AA is still unclear. Here we showed that angiotensin II (AngII) infusion increases the incidence of AA in leptin-deficient obese mice (ob/ob) and high-fat diet-induced obese mice with adventitial inflammation. Furthermore, transcriptome analysis revealed that platelet-derived growth factor D (PDGF-D) was highly expressed in the PVAT of ob/ob mice. Therefore, we hypothesized that PDGF-D mediates adventitial inflammation, which provides a direct link between PVAT dysfunction and AA formation in AngII-infused obese mice. We found that PDGF-D promotes the proliferation, migration, and inflammatory factors expression in cultured adventitial fibroblasts. In addition, the inhibition of PDGF-D function significantly reduced the incidence of AA in AngII-infused obese mice. More importantly, adipocyte-specific PDGF-D transgenic mice are more susceptible to AA formation after AngII infusion accompanied by exaggerated adventitial inflammatory and fibrotic responses. Collectively, our findings reveal a notable role of PDGF-D in the AA formation during obesity, and modulation of this cytokine might be an exploitable treatment strategy for the condition. PMID- 29794240 TI - Repeated Selection of Alternatively Adapted Haplotypes Creates Sweeping Genomic Remodeling in Stickleback. AB - Heterogeneous genetic divergence can accumulate across the genome when populations adapt to different habitats while still exchanging alleles. How long does diversification take and how much of the genome is affected? When divergence occurs in parallel from standing genetic variation, how often are the same haplotypes involved? We explore these questions using restriction site-associated DNA sequencing genotyping data and show that broad-scale genomic repatterning, fueled by copious standing variation, can emerge in just dozens of generations in replicate natural populations of threespine stickleback fish (Gasterosteus aculeatus). After the catastrophic 1964 Alaskan earthquake, marine stickleback colonized newly created ponds on seismically uplifted islands. We find that freshwater fish in these young ponds differ from their marine ancestors across the same genomic segments previously shown to have diverged in much older lake populations. Outside of these core divergent regions the genome shows no population structure across the ocean-freshwater divide, consistent with strong local selection acting in alternative environments on stickleback populations still connected by significant gene flow. Reinforcing this inference, a majority of divergent haplotypes that are at high frequency in ponds are detectable in the sea, even across great geographic distances. Building upon previous population genomics work in this model species, our data suggest that a long history of divergent selection and gene flow among stickleback populations in oceanic and freshwater habitats has maintained polymorphisms of alternatively adapted DNA sequences that facilitate parallel evolution. PMID- 29794239 TI - Multisite Concordance of DSC-MRI Analysis for Brain Tumors: Results of a National Cancer Institute Quantitative Imaging Network Collaborative Project. AB - BACKGROUND AND PURPOSE: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors. MATERIALS AND METHODS: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo-EPI sequence (TE/TR = 30/1200 ms; flip angle = 72 degrees ). Forty-nine low-grade (n = 13) and high grade (n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity. RESULTS: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 <= Lin concordance correlation coefficient <= 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%). CONCLUSIONS: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors. PMID- 29794244 TI - Cardiac auscultation poorly predicts the presence of valvular heart disease in asymptomatic primary care patients. AB - OBJECTIVE: Cardiac auscultation is a key clinical skill, particularly for the diagnosis of valvular heart disease (VHD). However, its utility has declined due to the widespread availability of echocardiography and diminishing emphasis on the importance of clinical examination. We aim to determine the contemporary accuracy of auscultation for diagnosing VHD in primary care. METHODS: Cardiac auscultation was undertaken by one of two experienced general practitioners (primary care/family doctors) in a subset of 251 asymptomatic participants aged >65 years undergoing echocardiography within a large community-based screening study of subjects with no known VHD. Investigators were blinded to the echocardiographic findings. Newly detected VHD was classified as mild (mild regurgitation of any valve or aortic sclerosis) or significant (at least moderate regurgitation or mild stenosis of any valve). RESULTS: Newly identified VHD was common, with mild disease in 170/251 participants (68%) and significant disease in 36/251 (14%). The sensitivity of auscultation was low for the diagnosis of mild VHD (32%) but slightly higher for significant VHD (44%), with specificities of 67% and 69%, respectively. Likelihood ratios were not statistically significant for the diagnosis of either mild or significant VHD in the overall cohort, but showed possible value for auscultation in non-overweight subjects (body mass index <25 kg/m2). CONCLUSION: Cardiac auscultation has limited accuracy for the detection of VHD in asymptomatic patients and is a poor diagnostic screening tool in primary care, particularly for overweight subjects. Ensuring easy access to echocardiography in patients with symptoms suggesting VHD is likely to represent a better diagnostic strategy. PMID- 29794245 TI - KLF4 Mediates the Effect of 5-ASA on the beta-Catenin Pathway in Colon Cancer Cells. AB - Mesalazine (5-ASA) is an aminosalicylate anti-inflammatory drug capable of inducing MU-protocadherin, a protein expressed by colorectal epithelial cells that is downregulated upon malignant transformation. Treatment with 5-ASA restores MU-protocadherin expression and promotes the sequestration of beta catenin to the plasma membrane. Here, we show that 5-ASA-induced MU-protocadherin expression is directly regulated by the KLF4 transcription factor. In addition, we suggest the existence of a dual mechanism whereby 5-ASA-mediated beta-catenin inhibition is caused by MU-protocadherin-dependent sequestration of beta-catenin to the plasma membrane and by the direct binding of KLF4 to beta-catenin. In addition, we found that 5-ASA treatment suppresses the expression of miR-130a and miR-135b, which target KLF4 mRNA, raising the possibility that this mechanism is involved in the increased expression of KLF4 induced by 5-ASA. Cancer Prev Res; 11(8); 503-10. (c)2018 AACR. PMID- 29794246 TI - Retraction for Fouhy et al., "Diffusible Signal Factor-Dependent Cell-Cell Signaling and Virulence in the Nosocomial Pathogen Stenotrophomonas maltophilia". PMID- 29794247 TI - Evaluation of a novel prognostic score based on thrombosis and inflammation in patients with sepsis: a retrospective cohort study. AB - BACKGROUND: Inflammation and thrombosis are involved in the development and progression of sepsis. A novel thrombo-inflammatory prognostic score (TIPS), based on both an inflammatory and a thrombus biomarker, was assessed for its ability to predict adverse outcomes of sepsis patients in the emergency department (ED). METHODS: This was a retrospective cohort study of sepsis patients. TIPS (range: 0-2) was predictive of adverse outcomes. Multivariable logistic regression analyses were performed to investigate the associations between TIPS and 28-day adverse outcomes. The study end points were mortality, mechanical ventilation (MV), consciousness disorder (CD) and admission to the intensive care unit (AICU). RESULTS: In total, 821 sepsis patients were enrolled; 173 patients died within the 28-day follow-up period. Procalcitonin and D-dimer values were used to calculate TIPS because they had the best performance in the prediction of 28-day mortality by receiver operating characteristic curves. The 28-day mortality and the incidence of MV, CD and AICU were significantly higher in patients with higher TIPS. Multivariable logistic regression analysis indicated TIPS was an independent predictor of 28-day mortality, MV and AICU. TIPS performed better than other prognostic scores, including quick sequential organ failure assessment, Modified Early Warning Score and Mortality in Emergency Department Sepsis Score for predicting 28-day mortality, and similar to the Acute Physiology and Chronic Health Evaluation II, but inferior to sequential organ failure assessment. CONCLUSIONS: TIPS is useful for stratifying the risk of adverse clinical outcomes in sepsis patients shortly after admission to the ED. PMID- 29794248 TI - External quality assessment programs in the context of ISO 15189 accreditation. PMID- 29794249 TI - Quality, origins and limitations of common therapeutic drug reference intervals. AB - Therapeutic drug monitoring (TDM) is used to manage drugs with a narrow window between effective and toxic concentrations. TDM involves measuring blood concentrations of drugs to ensure effective therapy, avoid toxicity and monitor compliance. Common drugs for which TDM is used include aminoglycosides for infections, anticonvulsants to treat seizures, immunosuppressants for transplant patients and cardiac glycosides to regulate cardiac output and heart rate. An essential element of TDM is the provision of accurate and clinically relevant reference intervals. Unlike most laboratory reference intervals, which are derived from a healthy population, TDM reference intervals need to relate to clinical outcomes in the form of efficacy and toxicity. This makes TDM inherently more difficult to develop as healthy individuals are not on therapy, so there is no "normal value". In addition, many of the aforementioned drugs are old and much of the information regarding reference intervals is based on small trials using methods that have changed. Furthermore, individuals have different pharmacokinetics and drug responses, particularly in the context of combined therapies, which exacerbates the challenge of universal TDM targets. This focused review examines the origins and limitations of existing TDM reference intervals for common drugs, providing targets where possible based on available guidelines. PMID- 29794250 TI - Blood sample quality. AB - Several lines of evidence now confirm that the vast majority of errors in laboratory medicine occur in the extra-analytical phases of the total testing processing, especially in the preanalytical phase. Most importantly, the collection of unsuitable specimens for testing (either due to inappropriate volume or quality) is by far the most frequent source of all laboratory errors, thus calling for urgent strategies for improving blood sample quality and managing data potentially generated measuring unsuitable specimens. A comprehensive overview of scientific literature leads us to conclude that hemolyzed samples are the most frequent cause of specimen non-conformity in clinical laboratories (40-70%), followed by insufficient or inappropriate sample volume (10-20%), biological samples collected in the wrong container (5-15%) and undue clotting (5-10%). Less frequent causes of impaired sample quality include contamination by infusion fluids (i.e. most often saline or glucose solutions), cross-contamination of blood tubes additives, inappropriate sample storage conditions or repeated freezing-thawing cycles. Therefore, this article is aimed to summarize the current evidence about the most frequent types of unsuitable blood samples, along with tentative recommendations on how to prevent or manage these preanalytical non-conformities. PMID- 29794251 TI - Chemical composition and antioxidant activity of phenolic compounds and essential oils from Calamintha nepeta L. AB - Background Essential oils, infusion and decoction extracts of Calamintha nepeta L. were evaluated for their bioactive substances (polyphenols and essential oils) and antioxidant activities. Methods The amounts of phenolic compounds were determined by colorimetric assays and identified by high performance and liquid chromatography coupled with ultraviolet detector (HPLC-UV) method. The chemical composition of essential oils was determined by gas-chromatography coupled with mass spectrometry (GC/MS) method. For the evaluation of the antioxidant activity of essential oils and extracts, two different assays (reducing power and DPPH radical scavenging activity) were used. Results Infusion extract presented the highest phenolic content, followed by the decoction one, while the lowest amount was observed in essential oils. The amount of flavonoids of the decocted extract was higher than that of the infused one. The phenolic profile of C. nepeta infusion and decoction extracts revealed the presence of 28 and 13 peaks, respectively. Four phenolics compounds were identified in infusion (gallic acid (GA), rosmarinic acid (RA), caffeine (C) and caffeic acid (CA)) and two were identified in decoction (GA and RA). The chemical composition of essential oils revealed the presence of 29 compounds, accounting for the 99.7% of the total oils. Major compounds of essential oil (EO) were trans-menthone (50.06%) and pulegone (33.46%). Infusion and decoction extracts revealed an interesting antioxidant activity which correlates positively with their total phenolic contents. Conclusions These results showed that Calamintha nepeta could be considered as a valuable source of phenolics and essential oils with potent antioxidant activity. PMID- 29794253 TI - What's new in preterm birth prediction and prevention? PMID- 29794252 TI - Wrist circumference as a novel predictor of obesity in children and adolescents: the CASPIAN-IV study. AB - Background Recent studies have discussed the application of wrist circumference as an easy-to-use predictor of general and abdominal obesity. The aim of the current study is to evaluate the association of wrist circumference with generalized and abdominal obesity and to determine its sex- and age-specific optimal cutoff points in association with generalized and abdominal obesity in a national sample of pediatric population. Methods This nationwide survey was conducted among 14,880 students, aged 6-18 years, selected through a multistage, random cluster sampling method from rural and urban areas of 30 provinces in Iran from 2011 to 2012. Anthropometric indices (weight, height, wrist circumference, waist circumference [WC], hip circumference [HC]) were measured by standard protocols using calibrated instruments. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. By considering the area under the curve (AUC) of the receiver operator characteristic (ROC) curves, we evaluated the association of wrist circumference with obesity indices and determined its sex- and age specific optimal cutoff points in association with obesity. AUC: 0.5, AUC: 0.5 0.65 and AUC: 0.65-1.0 were interpreted as equal to chance, moderately and highly accurate tests, respectively. Results Overall, 13,486 children and adolescents with a mean age of 12.47+/-3.36 years completed the study (participation rate of 90.6%). In both genders, wrist circumference had a significant correlation with anthropometric measures including weight, height, BMI, WC, HC and WHtR. In all age groups and both genders, wrist circumference performed relatively well in classifying individuals into overweight (AUC: 0.67-0.75, p<0.001), generalized obesity (AUC: 0.81-0.85, p<0.001) and abdominal obesity (AUC: 0.82-0.87, p<0.001). Conclusions Wrist circumference is suggested to be a useful index for assessing excess weight in the pediatric age group. Its easy measurement without the need of calculation ratios might make it as a routine measurement in daily clinical practice and in large epidemiological studies. PMID- 29794254 TI - Cannabidiol effects on prepulse inhibition in nonhuman primates. AB - Prepulse inhibition (PPI) of acoustic startle reflex is a well-established behavior paradigm to measure sensorimotor gating deficits. PPI is disrupted in several neuropsychiatric disorders, including schizophrenia. PPI tests can be used to screen new drugs for treatment of such disorders. In this review, we discuss how PPI paradigm can help in screening the therapeutic effects of cannabidiol (CBD). We look into recent literature about CBD effects on PPI response in animal models, especially in nonhuman primates. CBD has been shown to modify PPI in N-methyl d-aspartate receptor antagonist models for schizophrenia, both in rodents and in nonhuman primates. These results show CBD as a potential drug for the treatment of neurologic disorders that present alterations in sensorimotor system, such as schizophrenia. Moreover, the PPI paradigm seems to be a useful and relative simple paradigm to test the efficacy of CBD as a potential therapeutic drug. PMID- 29794255 TI - Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing. AB - BACKGROUND: A general trend towards conducting infectious disease serology testing in centralized laboratories means that quality control (QC) principles used for clinical chemistry testing are applied to infectious disease testing. However, no systematic assessment of methods used to establish QC limits has been applied to infectious disease serology testing. METHODS: A total of 103 QC data sets, obtained from six different infectious disease serology analytes, were parsed through standard methods for establishing statistical control limits, including guidelines from Public Health England, USA Clinical and Laboratory Standards Institute (CLSI), German Richtlinien der Bundesarztekammer (RiliBAK) and Australian QConnect. The percentage of QC results failing each method was compared. RESULTS: The percentage of data sets having more than 20% of QC results failing Westgard rules when the first 20 results were used to calculate the mean+/-2 standard deviation (SD) ranged from 3 (2.9%) for R4S to 66 (64.1%) for 10X rule, whereas the percentage ranged from 0 (0%) for R4S to 32 (40.5%) for 10X when the first 100 results were used to calculate the mean+/-2 SD. By contrast, the percentage of data sets with >20% failing the RiliBAK control limits was 25 (24.3%). Only two data sets (1.9%) had more than 20% of results outside the QConnect Limits. CONCLUSIONS: The rate of failure of QCs using QConnect Limits was more applicable for monitoring infectious disease serology testing compared with UK Public Health, CLSI and RiliBAK, as the alternatives to QConnect Limits reported an unacceptably high percentage of failures across the 103 data sets. PMID- 29794256 TI - Investigating adolescents' sweetened beverage consumption and Western fast food restaurant visits in China, 2006-2011. AB - Background China has undergone rapid Westernization and established dramatic social reforms since the early 21st century. However, health issues led to challenges in the lives of the Chinese residents. Western fast food and sweetened beverages, two food options associated with chronic diseases and obesity, have played key roles to alter adolescents' dietary patterns. This study aims to examine the association between adolescents' visits to Western fast food restaurants and sweetened beverage consumption. Methods Applying three waves of the China Health and Nutrition Study (CHNS) between 2006 and 2011 (n = 1063), we used generalized Poisson regression (GPR) to investigate the association between adolescents' Western fast food restaurant visits and sweetened beverage consumption, as the popularity of fast food and sweetened beverages has skyrocketed among adolescents in contemporary China. A linear-by-linear association test was used as a trend test to study general patterns between sweetened beverage consumption and Western fast food restaurant visits. We adjusted all models with sweetened beverage consumption frequency, four food preferences (fast food, salty snacks, fruits and vegetables), school status, gross household income, provinces, rural/urban regions, age and gender. Results From the results of the trend test, frequent sweetened beverage consumption was highly associated with more Western fast food restaurant visits among Chinese adolescents in the three waves (p < 0.001). Furthermore, we observed that adolescents, who had less than monthly sweetened beverage consumption or did not drink them at all, had much less likelihood of visiting Western fast food restaurants (p < 0.05), compared with those daily consumers. Conclusion Adolescents' sweetened beverage consumption was highly associated with Western fast food restaurant visits in contemporary China. Further actions are needed from the Chinese central government to create a healthier dietary environment for adolescents. PMID- 29794258 TI - Premature ovarian failure of autoimmune etiology in 46XX patients: is there a hope? AB - OBJECTIVES: To evaluate the efficacy of live bee stings at fertility points and acupuncture in treating symptoms and managing infertility in premature ovarian failure (POF) of autoimmune etiology. PATIENTS AND METHODS: Patients with primary POF were allocated randomly into two groups: group I: subjected to acupuncture at specific fertility points and group II: subjected to live bee stings at sites of fertility points. RESULTS: A total of 24 cases show significant reduction of Follicle stimulating hormone (FSH) level to normal range with gradual decline over the study duration: 13 cases in group I and 11 cases in group II. Eight cases got pregnant while the other 13 cases regained normal menses but still infertile. CONCLUSIONS: Both bee sting therapy and acupuncture were effective in reduction of FSH levels with restoration of regular menstrual patterns and restoration of fertility. The bee sting therapy was superior in the pregnancy rate, while acupuncture was superior in alleviation of symptoms. PMID- 29794257 TI - Integrated training (practicing, peer clinical training and OSCE assessment): a ladder to promote learning and training. AB - Introduction The teaching-learning process plays an effective role in training nursing students. Devising novel methods can lead to achievement of educational objectives as well as promotion of the clinical and practical training. The present study is aimed to determine the effect of integrated training, including practicing, peer clinical training and objective structured clinical examination (OSCE) assessment. Methods The interventional study was conducted on 58 freshman students. Two groups underwent a five-stage educational process; so that, all the students were trained and practiced in the skills lab, and their practical skills were investigated via the OSCE test. Afterwards, for clinical training in hospital, they were randomly divided into two groups of routine training (n = 26) and the peer-learning method (n = 32). Subsequently, in order to investigate the outcomes of the process, the OSCE test scores of the two training groups were compared both before and after the apprenticeship course. Results Scores of all the students were increased significantly at the end of the semester, but in terms of the total score of the clinical skills (14.79 +/- 1.52 vs. 18.52 +/- 0.84), the difference was insignificant (p = 0.29). Conclusion Training clinical skills along with OSCE practice and assessment can improve the nursing students' learning as well as their practical and clinical performance. Improvement of the students' performance can lead to high-quality care nursing. PMID- 29794259 TI - A proteomics analysis of adventitious root formation after leaf removal in lotus (Nelumbo nucifera Gaertn.). PMID- 29794260 TI - Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain. AB - Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramer-Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs= 0.42, n=28, p=0.031 and rs=-0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=-0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself. PMID- 29794261 TI - "When I feel the worst pain, I look like shit" - body image concerns in persistent pain. AB - Background and aims Persistent pain is a pervasive condition that is often associated with a distorted body image. Most research into pain and body image investigated neural or physiological correlates (e.g. phantom limb pain), and much less is known about the psychological experience of body image changes in response to pain such as appearance concerns. The aim was to examine body image concerns in people with persistent pain, in particular appearance concerns and related coping behaviours and appearance-related emotions such as anger and shame. Methods Design was cross-sectional and data was collected through in-depth semi-structured interviews with people suffering from persistent musculoskeletal pain (n=7; six females; age=19-56), and analysed with inductive thematic analysis (TA). Results Two main themes were identified: "Relationship to the painful body" and "Dissatisfaction with the body", each containing three subthemes, along with the side-theme "Appearance concerns affected by pain and mood". All participants reported appearance concerns, predominantly about their weight and related coping behaviours such as avoidance of mirrors, exercising or dieting and pain-induced mood changes that were associated with a negative body image. Conclusions People with persistent pain report appearance concerns, often related to pain-induced negative mood changes, and reduced functioning. It remains unclear to what extent attitudes towards the body change over time in accordance with pain. A wider concept of body image is required, including the perception of reduced functioning, related appraisals (e.g. "I look weak and old") and appearance investment. PMID- 29794262 TI - Correlation of clinical grading, physical tests and nerve conduction study in carpal tunnel syndrome. AB - Background and aims Carpal tunnel syndrome (CTS) is a common debilitating condition. As the reliability of CTS-specific physical tests and its clinical grading remain a matter of debate, we determined the correlations between these assessments with nerve conduction study (NCS). Methods In this cross-sectional study, patients with uni or bilateral CTS, which was confirmed in electrodiagnosis, were enrolled. Clinical grading was based on the modified criteria of the Italian CTS Study Group. Numeric Pain Rating Scale (NPRS) and Boston Questionnaire (BQ) were used. Physical tests [Phalen's, reverse Phalen's, Tinel's and manual carpal compression test (mCCT)] were performed by a single blinded neurologist. A p-value<0.05 was considered statistically significant. Results A total of 100 patients (age=47.48+/-11.44 years; 85% female) with 181 involved hands were studied. The majority of hands (59.7%) were classified as grade 2 of clinical grading. On NCS, hands with mild (64%), moderate (27%) and severe (9%) CTS were identified. Sensory (velocity, latency and amplitude) and motor parameters (latency and amplitude) were significantly correlated with clinical grades (p-value<0.001). The correlation of NPRS (p-value=0.009) and BQ (p-value<0.001) scores with NCS was significant. None of the physical tests were significantly correlated with NCS in terms of result or duration (p-value>0.05). Conclusions We found that physical tests are not a reliable screening method for evaluation of CTS severity. However, the BQ and clinical grading can be more valuable due to their significant correlation with NCS. Implications Physicians might benefit from employing clinical grading and BQ in practice for better assessment of CTS severity. PMID- 29794263 TI - Do pain-associated contexts increase pain sensitivity? An investigation using virtual reality. AB - Background and aims Pain is not a linear result of nociception, but is dependent on multisensory inputs, psychological factors, and prior experience. Since nociceptive models appear insufficient to explain chronic pain, understanding non nociceptive contributors is imperative. Several recent models propose that cues associatively linked to painful events might acquire the capacity to augment, or even cause, pain. This experiment aimed to determine whether contexts associated with pain, could modulate mechanical pain thresholds and pain intensity. Methods Forty-eight healthy participants underwent a contextual conditioning procedure, where three neutral virtual reality contexts were paired with either unpredictable noxious stimulation, unpredictable vibrotactile stimulation, or no stimulation. Following the conditioning procedure, mechanical pain thresholds and pain evoked by a test stimulus were examined in each context. In the test phase, the effect of expectancy was equalised across conditions by informing participants when thresholds and painful stimuli would be presented. Results Contrary to our hypothesis, scenes that were associated with noxious stimulation did not increase mechanical sensitivity (p=0.08), or increase pain intensity (p=0.46). However, an interaction with sex highlighted the possibility that pain associated contexts may alter pain sensitivity in females but not males (p=0.03). Conclusions Overall, our data does not support the idea that pain-associated contexts can alter pain sensitivity in healthy asymptomatic individuals. That an effect was shown in females highlights the possibility that some subgroups may be susceptible to such an effect, although the magnitude of the effect may lack real world significance. If pain-associated cues prove to have a relevant pain augmenting effect, in some subgroups, procedures aimed at extinguishing pain related associations may have therapeutic potential. PMID- 29794264 TI - The prevalence of neck-shoulder pain, back pain and psychological symptoms in association with daytime sleepiness - a prospective follow-up study of school children aged 10 to 15. AB - Background and aims Chronic and recurrent pain is prevalent in adolescents and generally girls report more pain symptoms than boys. Also, pain symptoms and sleep problems often co-occur. Pain symptoms have negative effects on school achievement, emotional well-being, sleep, and overall health and well-being. For effective intervention and prevention there is a need for defining factors associated with pain symptoms and daytime sleepiness. The aim of this longitudinal study was to investigate the prevalence and association between neck shoulder pain, back pain, psychological symptoms and daytime sleepiness in 10-, 12- and 15-year-old children. This study is the first that followed up the same cohort of children from the age of 10 to 15. Methods A cohort study design with three measurement points was used. Participants (n=568) were recruited from an elementary school cohort in a city of 1,75,000 inhabitants in South-Western Finland. Symptoms and daytime sleepiness were measured with self-administered questionnaires. Regression models were used to analyze the associations. Results Frequent neck-shoulder pain and back pain, and psychological symptoms, as well as daytime sleepiness, are already common at the age of 10 and increase strongly between the ages 12 and 15. Overall a greater proportion of girls suffered from pain symptoms and daytime sleepiness compared to boys. Daytime sleepiness in all ages associated positively with the frequency of neck-shoulder pain and back pain. The more that daytime sleepiness existed, the more neck-shoulder pain and back pain occurred. Daytime sleepiness at the age of 10 predicted neck-shoulder pain at the age of 15, and back pain at the age of 10 indicated that there would also be back pain at the age of 15. In addition, positive associations between psychological symptoms and neck-shoulder pain, as well as back pain, were observed. Subjects with psychological problems suffered neck-shoulder pain and back pain more frequently. Conclusions This study is the first study that has followed up the same cohort of children from the age of 10 to 15. The studied symptoms were all already frequent at the age of 10. An increase mostly happened between the ages of 12 and 15. Moreover, the self-reported daytime sleepiness at the age of 10 predicted neck-shoulder pain at the age of 15. More attention should be paid to the daytime sleepiness of children at an early stage as it has a predictive value for other symptoms later in life. Implications School nurses, teachers and parents are in a key position to prevent adolescents' sleep habits and healthy living habits. Furthermore, the finding that daytime sleepiness predicts neck-shoulder pain later in adolescence suggests that persistent sleep problems in childhood need early identification and treatment. Health care professionals also need take account of other risk factors, such as psychological symptoms and pain symptoms. The early identification and treatment of sleep problems in children might prevent the symptoms' development later in life. There is a need for an individuals' interventions to treat adolescents' sleep problems. PMID- 29794265 TI - The influence of isometric exercise on endogenous pain modulation: comparing exercise-induced hypoalgesia and offset analgesia in young, active adults. AB - Background and aims Impairment of endogenous analgesia has been associated with the development, maintenance and persistence of pain. Endogenous analgesia can be evaluated using exercise-induced hypoalgesia (EIH) and offset analgesia (OffA) paradigms, which measure temporal filtering of sensory information. It is not clear if these paradigms are underpinned by common mechanisms, as EIH and OffA have not previously been directly compared. A further understanding of the processes responsible for these clinically relevant phenomena may have future diagnostic and therapeutic utility in management of individuals with persistent pain conditions. The primary aim of this study was to investigate if there is a correlation between the magnitudes of EIH and OffA. The secondary aim of the study was to examine whether exercise influences OffA. Methods Thirty-six healthy, pain-free participants were recruited. EIH was evaluated using pressure pain thresholds (PPT) and pain ratings to suprathreshold pressure stimuli over tibialis anterior and the cervical spine. OffA evaluation utilised a three-step protocol, whereby individualised heat pain thermal stimuli [Numerical Rating Scale (NRS)=50/100] were applied (T1), before increasing 1 degrees C (T2), followed by 1 degrees C reduction (T3). The magnitude of OffA was calculated as the percentage reduction in the NRS from T2 to T3. PPT/suprathreshold pain ratings and OffA measures were recorded, before and after 5 min of isometric quadriceps exercise performed at 20-25% maximum voluntary contraction (MVC); and following a 15 min rest period. Data were analysed using repeated measures (RM) ANCOVA and correlational analyses. Results There was no correlation between EIH measures (PPTs or pain ratings to suprathreshold pressure stimuli over tibialis anterior or the cervical spine) and OffA (p>0.11 for all). OffA was induced and not modulated by exercise (p=0.28). Conclusions Five minutes of 20-25% MVC lower limb isometric exercise provided non-pharmacological pain modulation in young, active adults. Magnitude of EIH was not correlated with that of OffA, and exercise did not influence magnitude of OffA. Implications These results suggest that in young, pain-free individuals, separate testing of these two paradigms is required to comprehensively evaluate efficacy of endogenous analgesia. If these results are replicated in patient populations, alternative or complementary methods to exercise interventions may be required to modulate impaired OffA. PMID- 29794266 TI - Chronic pelvic pain - pain catastrophizing, pelvic pain and quality of life. AB - Background and aims Chronic pelvic pain (CPP) impacts significantly on the lives of women. Negative coping responses such as pain catastrophizing are thought to be significant in predicting both pain severity and outcome. The combined effect of the individual's response to pain and its severity on their quality of life (QoL) has not been well studied in women with CPP. Aims were to determine the prevalence of pain catastrophizing in women with CPP and to examine the associations between pain catastrophizing and levels of dysmenorrhea, non cyclical pelvic pain, dyspareunia, dysuria, dyschezia and QoL. Methods A cross sectional study including women aged 18-50 years, referred to a tertiary gynecology outpatients department at an Australian women's hospital in 2015. Participants completed questionnaires including: pain catastrophizing scale (PCS); pelvic pain levels in the prior 3 months; and the World Health Organisation Quality of life - Bref Questionnaire (WHOQoL-Bref). Statistical analysis was performed using STATA (StataCorp, USA Version13). Results Participants (n = 115) had a median age of 29.0 [interquartile range (IQR): 23.0 38.0] years. The Pain catastrophizing score revealed that 60/113 [95% confidence interval (CI): 48.6, 71.2] of participants had a clinically relevant total score >=30. There were statistically significant positive correlations between pain catastrophizing scores and pelvic pain levels in all five pain categories studied, dysmenorrhea (rho = 0.37, p = 0.0001), non-cyclical pelvic pain (rho = 0.46, p<0.0001), dyspareunia (rho = 0.32, p = 0.0008), dysuria (rho = 0.32, p = 0.0005) and dyschezia (rho = 0.38, p = 0.0012). Participants who reported maximal pain levels (5/5) had significantly higher median pain catastrophizing scores when compared to those who reported no pain (0/5) in all categories. Overall QoL was considered as "good" in 71/113 (95% CI: 60.1, 81.0) participants and "poor" in 42/113 (95% CI: 32.0, 53.0) participants. Comparison to Australian female norms revealed significantly lower QoL scores in the physical domain, across all ages, and in psychological domain for those aged <30 and 30-40 years. There was a significant association between increased catastrophizing scores and reduced odds of good QoL. An increase in PCS by one point is associated with a 6.3% decrease in the odds of good QoL [odds ratio (OR) per one-point increase: 0.94 (95% CI: 0.89, 0.98), p = 0.008]. Conclusions Pain catastrophizing is prevalent at clinically relevant levels in women with CPP across all domains. It is associated with higher pain levels and decreased QoL. Implications There is potential for further studies to investigate the predictive nature of pain catastrophizing and management targeting catastrophizing to improve outcomes in women with CPP. PMID- 29794267 TI - The role of pain in chronic pain patients' perception of health-related quality of life: a cross-sectional SQRP study of 40,000 patients. AB - Background and aims Health-related quality of life (Hr-QoL) reflects the burden of a condition on an overarching level. Pain intensity, disability and other factors influence how patients with chronic pain perceive their condition, e.g. Hr-QoL. However, the relative importance of these factors is unclear and there is an ongoing debate as to what importance pain measures have in this group. We investigated the importance of current pain level and mood on aspects of Hr-QoL in patients with chronic pain and investigated whether such relationships are influenced by demographics. Methods Data was obtained from the Swedish Quality Registry for Pain Rehabilitation (SQRP), between 2008 and 2016 on patients >=18 years old who suffered from chronic pain and were referred to participating specialist clinics. Dependent variables were general Hr-QoL [using two scales from European Quality of Life instrument: EQ5D Index and the European Quality of Life instrument health scale (EQ thermometer)] and specific Hr-QoL [from the Short Form Health Survey (SF36) the physical component summary (SF36-PCS) and the mental (psychological) component summary (SF36-MCS)]. Independent variables were sociodemographic variables, pain variables, psychological distress and pain attitudes. Principal component analysis (PCA) was used for multivariate correlation analyses of all investigated variables and Orthogonal Partial Least Square Regression (OPLS) for multivariate regressions on health aspects. Results There was 40,518 patients (72% women). Pain intensity and interference showed the strongest multivariate correlations with EQ5D Index, EQ thermometer and SF36-PCS. Psychological distress variables displayed the strongest multivariate correlations with SF36-MCS. Demographic properties did not significantly influence variations in the investigated Hr-QoL variables. Conclusions Pain, mood and pain attitudes were significantly correlated with Hr-QoL variables, but these variables cannot explain most of variations in Hr-QoL variables. The results pinpoint that broad assessments (including pain intensity aspects) are needed to capture the clinical presentation of patients with complex chronic pain conditions. PMID- 29794268 TI - Adding steroids to lidocaine in a therapeutic injection regimen for patients with abdominal pain due to anterior cutaneous nerve entrapment syndrome (ACNES): a single blinded randomized clinical trial. AB - Background and aims Anterior cutaneous nerve entrapment syndrome (ACNES) may result in chronic abdominal pain. Therapeutic options include local injection therapy. Data on the efficacy of adding corticosteroids to these injections is lacking. Methods Patients >=18 years with ACNES were randomized to receive an injection of lidocaine with (LC-group) or without (LA-group) the addition of methylprednisolone into the point of maximal abdominal wall pain. Pain was recorded using a numeric rating scale (NRS: 0-10) and a verbal rating scale (VRS: 0=no pain, 5=unbearable pain) at baseline and 6 weeks after the start of a bi weekly injection regimen consisting of a total of three injections. A minimal 50% reduction on NRS and/or two points on VRS were considered successful responses. Results Between February 2014 and August 2016, 136 patients (median age 46 year, range 18-79, 75% females) were randomized (68 vs. 68). The proportion of patients demonstrating a successful response after 6 weeks did not significantly differ between groups (LA 38%, LC 31%, p=0.61). At 12 weeks, the number of patients still experiencing a minimal 50% pain relief had decreased but no group difference was observed (LA 20%, LC 18%, p=0.80). Minor side effects included temporary increase of pain, tenderness at injection sites or transient malaise (LA23/68, LC 29/68, p=0.46). Conclusions Adding corticosteroids to a lidocaine does not increase the proportion of ACNES patients with a successful response to injection therapy. Lidocaine alone can provide long term pain relief after one or multiple injections, in approximately 1 of 5 patients. PMID- 29794269 TI - Wireless peripheral nerve stimulation for complex regional pain syndrome type I of the upper extremity: a case illustration introducing a novel technology. AB - Background Complex regional pain syndrome (CRPS) is a debilitating painful disorder, cryptic in its pathophysiology and refractory condition with limited therapeutic options. Type I CRPS with its variable relationship to trauma has often no discernible fractures or nerve injuries and remains enigmatic in its response to conservative treatment as well as the other limited interventional therapies. Neuromodulation in the form of spinal cord and dorsal root ganglion stimulation (SCS, DRGS) has shown encouraging results, especially of causalgia or CRPS I of lower extremities. Upper extremity CRPS I is far more difficult. Objective To report a case of upper extremity CRPS I treated by wireless peripheral nerve stimulation (WPNS) for its unique features and minimally invasive technique. The system does not involve implantation of battery or its connections. Case report A 47 year old female patient presented with refractory CRPS I following a blunt trauma to her right forearm. As interventional treatment in the form of local anesthetics (Anesthesia of peripheral branches of radial nerve) and combined infusions of ketamine/lidocaine failed to provide any significant relief she opted for WPNS treatment. Based on the topographic distribution, two electrodes (Stimwave Leads: FR4A-RCV-A0 with tines, Generation 1 and FR4A-RCV-B0 with tines, Generation 1), were placed along the course of radial and median nerves under ultrasonography monitoring and guided by intraoperative stimulation. This procedure did not involve implantation of extension cables or the power source. At a frequency of 60 Hz and 300 MUs the stimulation induced paresthesia along the distribution of the nerves. Therapeutic relief was observed with high frequency (HF) stimulation (HF 10 kHz/32 MUs, 2.0 mA) reducing her pain from a visual analogue scale (VAS) score of 7-4 postoperatively. Three HF stimulations programs were provided at the time of discharge, as she improved in her sensory impairment to touch, pressure and temperature at her first follow up visit. At 5-months she was able to drive, did not require opioids and allodynia disappeared. Conclusions In a case with difficult CRPS I involving upper extremity, a minimally invasive WPNS of radial and median nerves provided good symptomatic relief. The procedure was tolerated well and both electrodes remained in place without any adverse events. Implications In view of the very limited options currently available to manage CRPS, WPNS can be a promising therapeutic modality. PMID- 29794270 TI - Patients' pre-operative general and specific outcome expectations predict postoperative pain and function after total knee and total hip arthroplasties. AB - Background and aims Previous studies have suggested there is an association between preoperative expectations about the outcome and outcomes of total knee and total hip arthroplasty (TKA/THA). However, expectations have been rarely examined on their clinical relevance relative to other well-known predictive factors. Furthermore expectations can be measured on a more generic level (e.g. does one expect their symptoms to improve after surgery) or on a more specific level (e.g. does one expect to be able to squat again after surgery). Aim of this study was to examine whether patients' general and specific preoperative outcome expectations predict function and pain 12-months after TKA/THA, when assessed as one of the candidate predictive variables alongside other relevant clinical and sociodemographic variables. Moreover, we explored whether a more generic or a more specific assessment of expectations would better predict outcome. Methods A prospective cohort study on consecutive TKA/THA patients, with assessments done preoperatively and 12-months postoperative. Primary outcomes were the knee injury and osteoarthritis outcome score (KOOS) and hip injury and osteoarthritis outcome score (HOOS) activities of daily living (ADL) and pain subscale scores at 12 months. The pain subscales consist of nine-(KOOS) and 10-(HOOS) items and the ADL of 17 items. Patients' preoperative outcome expectations were measured with the credibility expectancy questionnaire (CEQ), which contains three items scored on a 0-9 scale and sum score 0-27 and the Hospital for Special Surgery expectations surveys (HSS expectation surveys) for 17(TKA) or 18(THA) outcomes on 0-4 scale. Other candidate predictors: preoperative pain and function as measured with HOOS/KOOS, sex, age, education level, body mass index, Kellgren/Lawrence score, preoperative mental health and treatment credibility as measured with CEQ. Eight prediction models were constructed using multivariate linear regression analysis with a backward selection procedure. Results The 146 TKA patients included in this study had a mean age of 66.9 years (SD 9.2) and 69% was female. The 148 THA patients had a mean age 67.2 (SD 9.5) and 57% was female. Mean outcomes: postoperative HOOS-ADL 84.3 (SD 16.6), pain 88.2 (SD 15.4), KOOS-ADL 83.9 (SD 15.8) and pain 83.6 (SD 17.1). CEQ-expectancy median was in THA 23 (IQR 21;24) and TKA 23 (IQR 20;24). HSS-expectation surveys function was for THA 21.0 (18.0;24.0) and 19.0 (14.0;22.0) in TKA. Patients' outcome expectations were consistently part of the combination of variables that best predicted outcomes for both TKA/THA 1-year post-operatively. Expectations alone explained between 17.0 and 30.3% of the variance in outcomes. The CEQ expectancy subscale explained more variance of postoperative function in TKA and of function and pain in THA as compared to the HSS expectation surveys. Conclusions In planning of surgical treatment, orthopedic surgeons should take a range of variables into account of which the patient's expectations about outcome of surgery is one. The CEQ expectancy subscale predicted outcomes slightly better as the HSS expectation surveys, but differences in predictive value of the two measurements were too small to prefer between the two. Future studies are advised to replicate these findings and externally validate the models presented. PMID- 29794271 TI - Differences in Swedish and Australian medical student attitudes and beliefs about chronic pain, its management, and the way it is taught. AB - Background and aims Medical students receive training in the management of chronic pain, but the training is often suboptimal. Considering that the basis for physician's knowledge is their medical education, it is important to explore the attitudes and beliefs of medical students with respect both to chronic pain management and to their views on current pain education. Therefore, the aim of this study was to compare Swedish and Australian medical student's attitudes and beliefs about patients with chronic pain, and their perceptions regarding their chronic pain management education. Methods An online survey was conducted with final year Australian and Swedish medical students from two different universities between December 2016 and February 2017. Attitudes and beliefs towards chronic pain patients were measured using the Health Care Providers' Pain and Impairment Scale (HC-PAIRS). A thematic analysis was conducted on open end questions regarding their views on their education and important skills for chronic pain management. Results A total of 57 Swedish and 26 Australian medical students completed the HC-PAIRS scale. The Swedish medical students showed statistically significantly lower total mean HC-PAIRS scores compared to Australian medical students (46 and 51, respectively). Australian students had statistically significantly higher scores than the Swedish students for two of four factors: functional expectations and need for cure, whereas no significant differences were seen for the factors social expectations or for projected cognition. From the open end questions it was evident that final year medical students are knowledgeable about key chronic pain items described in clinical guidelines. However, both cohorts described their chronic pain training as poor and in need of improvement in several areas such as more focus on the biopsychosocial model, working in multidisciplinary teams, seeing chronic pain patients and pharmacological training. Conclusions Attitudes and beliefs are formed during medical education, and our study exploring attitudes of medical students towards chronic pain and how it is taught have provided valuable information. Our survey provided detailed and cohesive suggestions for education improvement that also are in line with current clinical guidelines. This study indicates that the Swedish final year students have a more positive attitude towards chronic pain patients compared to their Australian counterparts. The majority of students in both cohorts perceived chronic pain management education in need of improvement. Implications This study highlights several areas of interest that warrant further investigation, for example, the impact of a changed medical curriculum in alignment with these clinical guidelines requested by students in this survey, and correspondingly if their attitudes towards chronic pain patients can be improved through education. Further, we conclude that it would be valuable to align the implementation of the HC-PAIRS instrument in order to achieve comparable results between future studies. PMID- 29794273 TI - The neglected role of distress in pain management: qualitative research on a gastrointestinal ward. AB - Background and aims Pain management for hospital inpatients remains suboptimal. Previously identified barriers to optimal pain management include staff communication difficulties, confusion around pain management roles and a lack of suitable resources for clinical staff. The emotional, relational and contextual complexities of gastrointestinal (GI) pain create particular challenges for frontline clinical staff attempting to implement a biopsychosocial approach to its management. The current study took place over 2 years, comprised an ethnographic and a feedback phase, and aimed to examine pain management processes with clinical staff in order to generate hypotheses and initiatives for improvement. This paper focuses on two overarching themes identified in the ethnographic phase of the study, centred on the neglected role of both staff and patient distress in GI pain management. Methods Grounded theory and thematic analysis methods were used as part of action research, which involves collaborative working with clinical staff. The study took place on a 60 bed GI ward in a university hospital in London. Participants were clinical staff who were either ward-based or involved in the care of particular patients. This latter group included doctors, nurses, psychologists and physiotherapists from the Acute and Complex Pain Teams. Qualitative data on pain management processes was gathered from staff interviews, consultation groups, and observations of patient-staff interactions. Recruitment was purposive and collaborative in that early participants suggested targets and staff groups for subsequent enquiry. Following the identification of initial ethnographic themes, further analysis and the use of existing literature led to the identification of two overarching pain management processes. As such the results are divided into three sections: (i) illustration of initial ethnographic themes, (ii) summary of relevant theory used, (iii) exploration of hypothesised overarching processes. Results Initially, two consultation groups, five nursing staff and five junior doctors, provided key issues that were included in subsequent interviews (n=18) and observations (n=5). Initial ethnographic themes were divided into challenges and resources, reflecting the emergent structure of interviews and observations. Drawing on attachment, psychodynamic and evolutionary theories, themes were then regrouped around two overarching processes, centred on the neglected role of distress in pain management. The first process elucidates the lack of recognition during pain assessment of the emotional impact of patient distress on staff decision-making and pain management practice. The second process demonstrates that, as a consequence of resultant staff distress, communication between staff groups was fraught and resources, such as expert team referral and pharmacotherapy, appeared to function, at times, to protect staff rather than to help patients. Interpersonal skills used by staff to relieve patient distress were largely outside systems for pain care. Conclusions Findings suggest that identified "barriers" to optimal pain management likely serve an important defensive function for staff and organisations. Implications Unless the impact of patient distress on staff is recognised and addressed within the system, these barriers will persist. PMID- 29794272 TI - An experimental investigation of the relationships among race, prayer, and pain. AB - Background and aims Compared to White individuals, Black individuals demonstrate a lower pain tolerance. Research suggests that differences in pain coping strategies, such as prayer, may mediate this race difference. However, previous research has been cross-sectional and has not determined whether prayer in and of itself or rather the passive nature of prayer is driving the effects on pain tolerance. The aim of this study was to clarify the relationships among race, prayer (both active and passive), and pain tolerance. Methods We randomly assigned 208 pain-free participants (47% Black, 53% White) to one of three groups: active prayer ("God, help me endure the pain"), passive prayer ("God, take the pain away"), or no prayer ("The sky is blue"). Participants first completed a series of questionnaires including the Duke University Religion Index, the Coping Strategies Questionnaire-Revised (CSQ-R), and the Pain Catastrophizing Scale. Participants were then instructed to repeat a specified prayer or distractor coping statement while undergoing a cold pressor task. Cold pain tolerance was measured by the number of seconds that had elapsed while the participant's hand remained in the cold water bath (maximum 180 s). Results Results of independent samples t-tests indicated that Black participants scored higher on the CSQ-R prayer/hoping subscale. However, there were no race differences among other coping strategies, religiosity, or catastrophizing. Results of a 2 (Race: White vs. Black)*3 (Prayer: active vs. passive vs. no prayer) ANCOVA controlling for a general tendency to pray and catastrophizing in response to prayer indicated a main effect of prayer that approached significance (p=0.06). Pairwise comparisons indicated that those in the active prayer condition demonstrated greater pain tolerance than those in the passive (p=0.06) and no prayer (p=0.03) conditions. Those in the passive and no prayer distractor conditions did not significantly differ (p=0.70). There was also a trending main effect of race [p=0.08], with White participants demonstrating greater pain tolerance than Black participants. Conclusions Taken together, these results indicate that Black participants demonstrated a lower pain tolerance than White participants, and those in the active prayer condition demonstrated greater tolerance than those in the passive and no prayer conditions. Furthermore, Black participants in the passive prayer group demonstrated the lowest pain tolerance, while White participants in the active prayer group exhibited the greatest tolerance. Results of this study suggest that passive prayer, like other passive coping strategies, may be related to lower pain tolerance and thus poorer pain outcomes, perhaps especially for Black individuals. On the other hand, results suggest active prayer is associated with greater pain tolerance, especially for White individuals. Implications These results suggest that understanding the influence of prayer on pain may require differentiation between active versus passive prayer strategies. Like other active coping strategies for pain, active prayer may facilitate self-management of pain and thus enhance pain outcomes independent of race. Psychosocial interventions may help religiously-oriented individuals, regardless of race, cultivate a more active style of prayer to improve their quality of life. PMID- 29794274 TI - Pain mapping of the anterior knee: injured athletes know best. AB - Background and aims Research investigating differences in pain location and distribution across conditions is lacking. Mapping a patient's pain may be a useful way of understanding differences in presentations, however the use of pain mapping during a pain provocation task has not been investigated. The aim of this study was to assess the reliability of patient and clinician rated pain maps during a pain provocation task for the anterior knee. Methods Participants were recruited from a larger study of professional Australian rules football players (n=17). Players were invited to participate if they reported a current or past history of patellar tendon pain. No clinical diagnosis was performed for this reliability study. Participants were asked to point on their own knee where they usually experienced pain, which was recorded by a clinician on a piloted photograph of the knee using an iPad. Participants then completed a single leg decline squat (SLDS), after which participants indicated where they experienced pain during the task with their finger, which was recorded by a clinician. Participants then recorded their own self-rated pain map. This process was repeated 10 min later. Pain maps were subjectively classified into categories of pain location and spread by two raters. Pain area was quantified by the number of pixels shaded. Intra- and inter-rater reliability (between participants and clinicians) were analysed for pain area, similarity of location as well as subjective classification. Results Test-retest reliability was good for participants (intraclass correlation coefficients [ICC]=0.81) but only fair for clinicians (ICC=0.47) for pain area. There was poor agreement between participants and clinicians for pain area (ICC=0.16) and similarity of location (Jaccard index=0.19). Clinicians had good inter- and intra-rater reliability of classification of pain spread (k=0.75 and 0.67). Conclusions Participant completed pain maps were more reliable than clinician pain maps. Clinicians were reliable at classifying pain based on location and type of spread. Implications Clinicians should ask patients to complete their own pain maps following a pain provocation test, to elicit the most reliable and consistent understanding of their pain perception. PMID- 29794275 TI - The peer effect on pain tolerance. AB - Background and aims Twin studies have found that approximately half of the variance in pain tolerance can be explained by genetic factors, while shared family environment has a negligible effect. Hence, a large proportion of the variance in pain tolerance is explained by the (non-shared) unique environment. The social environment beyond the family is a potential candidate for explaining some of the variance in pain tolerance. Numerous individual traits have previously shown to be associated with friendship ties. In this study, we investigate whether pain tolerance is associated with friendship ties. Methods We study the friendship effect on pain tolerance by considering data from the Tromso Study: Fit Futures I, which contains pain tolerance measurements and social network information for adolescents attending first year of upper secondary school in the Tromso area in Northern Norway. Pain tolerance was measured with the cold-pressor test (primary outcome), contact heat and pressure algometry. We analyse the data by using statistical methods from social network analysis. Specifically, we compute pairwise correlations in pain tolerance among friends. We also fit network autocorrelation models to the data, where the pain tolerance of an individual is explained by (among other factors) the average pain tolerance of the individual's friends. Results We find a significant and positive relationship between the pain tolerance of an individual and the pain tolerance of their friends. The estimated effect is that for every 1 s increase in friends' average cold-pressor tolerance time, the expected cold-pressor pain tolerance of the individual increases by 0.21 s (p-value: 0.0049, sample size n=997). This estimated effect is controlled for sex. The friendship effect remains significant when controlling for potential confounders such as lifestyle factors and test sequence among the students. Further investigating the role of sex on this friendship effect, we only find a significant peer effect of male friends on males, while there is no significant effect of friends' average pain tolerance on females in stratified analyses. Similar, but somewhat lower estimates were obtained for the other pain modalities. Conclusions We find a positive and significant peer effect in pain tolerance. Hence, there is a significant tendency for students to be friends with others with similar pain tolerance. Sex stratified analyses show that the only significant effect is the effect of male friends on males. Implications Two different processes can explain the friendship effect in pain tolerance, selection and social transmission. Individuals might select friends directly due to similarity in pain tolerance, or indirectly through similarity in other confounding variables that affect pain tolerance. Alternatively, there is an influence effect among friends either directly in pain tolerance, or indirectly through other variables that affect pain tolerance. If there is indeed a social influence effect in pain tolerance, then the social environment can account for some of the unique environmental variance in pain tolerance. If so, it is possible to therapeutically affect pain tolerance through alteration of the social environment. PMID- 29794276 TI - Friends in pain: pain tolerance in a social network. PMID- 29794277 TI - Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial. AB - BACKGROUND AND AIMS: Acute pain episodes associated with sickle cell disease (SCD) are very difficult to manage effectively. Opioid tolerance and side effects have been major roadblocks in our ability to provide these patients with adequate pain relief. Ketamine is cheap, widely safe, readily available drug, with analgesic effects at sub-anesthetic doses and has been used in wide range of surgeries, pediatric burns dressing change and cancer related pain however, literature concerning its use in sickle cell crises is still limited in our setting. This study aimed to establish if 1 mg/kg of intravenous ketamine is non inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. METHODS: We performed an institutional review board-approved randomized, prospective, double-blinded, active-control, non-inferiority trial at the national referral sickle cell center. Children between 7 and 18 years of age with severe painful sickle cell crisis, defined by numerical rating scale score of greater or equal to 7 were enrolled. Patients were consented and randomized to receive, either IV ketamine (LDK) 1 mg/kg or IV morphine (MOR) 0.1 mg/kg as an infusion over 10 min. The primary endpoint is maximal change in Numerical Rating Scale (NRS) pain score. Secondary outcomes were, incidence of adverse effects, optimal time to and duration of action of ketamine and incidence of treatment failures by treatment group. A clinically meaningful difference in validated pain scores was defined as 1.3 units. Assuming both treatments are on average equal, a sample size of 240 patients (120 per group) provided 95% power to demonstrate that IV LDK is non-inferior to IV morphine with a 0.05 level of significance and a 10% non-inferiority margin. All analyses were based on a modified intention to treat. This trial was registered with clinicaltrials.gov NCT02434939. RESULTS: Two hundred and forty patients were enrolled (LDK120, MOR120). Demographic variables and baseline NRS scores (8.9 vs. 9.2) were similar. LDK was comparable to MOR in the maximum change in NRS scores, 66.4% vs. 61.3% (MD 5.5; 95% CI -2.2 to -13.2). Time to achieve maximum reduction in NRS pain scores was at 19.8 min for LDK and 34.1 min for MOR. The average duration of action for LDK was 60 min. MOR had more patients still at maximum effect at 120 min (45.8% vs. 37.5%; RR 1.2; 95% CI 0.9-1.7). LDK patients were 11.3 times more likely to develop side effects, though were transient, anticipated and non-life threatening (37.5% vs. 3.3%). MOR had significantly more treatment failures 40% vs. 28.3% (RR 0.7; 95% CI 0.5-1.03, p=0.07) Vital signs and sedation scores were similar in both groups. CONCLUSIONS: Intravenous LDK at 1 mg/kg provides comparable analgesic effectiveness as IV MOR in the acute treatment of severe painful sickle cell crisis in children in the day care sickle cell center. However, it is associated with a high incidence of several transient, non-life threatening mild side effects. IMPLICATIONS: Intravenous ketamine at 1 mg/kg can be a reliable alternative to morphine in the management of severe painful sickle cell crisis especially in a resource limited area where morphine is not readily available. PMID- 29794278 TI - A case report of a thalamic stroke associated with sudden disappearance of severe chronic low back pain. AB - BACKGROUND: Chronic pain conditions are associated with neuroplasticity within the central nervous system. In most patients the maladaptive consequence of neuroplasticity supports prolonged course of chronic pain, despite the absence of a commensurate etiology. From a pain neuromatrix perspective it can involve three different circuits within the central nervous system; the classical sensory pathway, the limbic system pathway, and the associative pathways involving the parietal cortical connections. Although this can be conceptualized as a fluid system composed of several interacting networks, it can be broadly separated into a nociceptive specific network of spino-thalamic neurons and second order neurons beyond thalamus that are not nociceptor specific. Thalamus acts as an important relay station that conveys nociceptive signaling to higher centres. Neuroplastic changes can potentially involve any parts within this neuromatrix. It is very uncommon to observe the sudden disappearance of such a chronic pain condition. METHODS AND RESULTS: In this case report, the author describes the clinical course of a patient with severe chronic low back pain (CLBP), whose pain suddenly disappeared after a stroke involving his left thalamus. Although extremely rare, existing case reports of such disappearance of pain with a secondary stroke in patients suffering from central post stroke pain (CPSP) are reviewed. The author further postulates hypotheses that could potentially explain this phenomenon based on the existing knowledge. CONCLUSIONS AND IMPLICATIONS: Although extremely rare and unpredictable, a thalamic stroke involving areas that are involved in chronic pain signaling can potentially lead to disappearence of an existing chronic pain condition. This is the first case report of such sudden disappearence of CLBP with well established nociceptive pathology supported by clinical and imaging findings. This unique case report could potentially generate ideas for future research and clinical treatment in the field of neuromodulation and brain stimulation. PMID- 29794279 TI - Physical activity during work and leisure show contrasting associations with fear avoidance beliefs: cross-sectional study among more than 10,000 wage earners of the general working population. AB - BACKGROUND AND AIMS: The association between different types of physical activity and fear-avoidance beliefs remains unclear. This study investigates the association between work-related and leisure-time physical activity with fear avoidance beliefs in the general working population. METHODS: Currently employed wage earners (n=10,427) from the 2010 round of the Danish Work Environment Cohort Study replied to questions about work, lifestyle and health. General linear models controlling for lifestyle, psychosocial work factors, education, pain, medication-use and chronic diseases tested associations of work-related and leisure-time physical activity (explanatory variables) with fear-avoidance beliefs (outcome variable, scale 0-100). RESULTS: The level of fear-avoidance was 41.7 (SD 27.3), 38.0 (SD 26.9) and 54.3 (SD 27.7) among the general working population, a subgroup of pain-free individuals, and a subgroup with back disease, respectively. In the general working population, the level of fear avoidance among those with low, moderate and high physical activity during leisure were 47 [95% confidence intervals (CI) 45-49], 44 (95% CI 42-46) and 43 (95% CI 41-45), and physical activity at work were 40 (95% CI 39-42), 44 (95% CI 42-46) and 49 (95% CI 48-51), respectively. Individuals with back disease and a high level of physical activity at work showed the overall highest level of fear avoidance whereas pain-free individuals with a low level of physical activity at work showed the overall lowest level of fear-avoidance. CONCLUSIONS: Physical activity during work and leisure shows contrasting associations with fear avoidance beliefs. While high physical activity during leisure is associated with lower levels, high physical activity at work is associated with higher levels of fear-avoidance. IMPLICATIONS: The present results may reflect some deeply rooted negative beliefs about pain and work in the population. On the societal level, campaigns may be a possible way forward as these have shown to improve beliefs about musculoskeletal pain and work. PMID- 29794280 TI - Repetitive nerve block for neuropathic pain management: a case report. AB - Schwannoma is a common neoplasm in the peripheral and central nervous systems. Sciatic nerve schwanommas are rare. We report the case of a 50-year-old woman who was referred for treatment of persistent neuropathic pain in the left lower limb after resection of a schwannoma on the left S1 nerve root. The patient's history goes back when she was 27 years old and started to have electric-like pain in her lower left limb upon intercourse. Examination revealed a left ovarian cyst which was surgically removed. Her pain persisted despite taking nonsteroidal anti inflammatory drugs (NSAIDs). Several years later a schwannoma on the left S1 nerve root was detected. The patient had surgical excision of the left S1 nerve root at the plexus along with the schwannoma. Following the surgery, she experienced pain upon sitting and touch, and had a limp in her left leg. She was prescribed NSAIDs, antidepressant and pregabalin. Despite the pharmacological treatment, the patient had persistent mild pain. Upon physical examination, the incision from her previous surgery was 4 cm away from the sacral midline and parallel to S1 and S2. The length of the incision was 3 cm. The patient had severe allodynia upon palpation at the area between S1 and L5 and the visual analog scale (VAS) score increased from 3 to 10. She had severe pain at rest and movement. Her neurologic exam revealed that the left lower extremity motor power showed mild weakness in the leg abduction, foot eversion, plantar and toes flexion, and in the hip extension. The sensory exam showed severe reduction in pinprick and temperature sensation in the lateral aspect of foot, lower leg and dorsolateral thigh and buttocks. Nerve stimulator guided injection was performed at the pain trigger point being 1 cm above the midline of the incision. Upon nerve stimulation the contraction of the gluteal muscle was observed. Then, 20 mL of the anesthetic mixture were injected. The patient had immediate pain relief after the block (VAS 1/10). She remained pain free for 15 days after which pain reappeared but with less severity (3/10). Repetitive sciatic nerve block was performed in a progressive manner and was shown to be effective in managing neuropathic pain. PMID- 29794281 TI - Good news in the new year - New publisher of the PubMed-indexed Scandinavian Journal of Pain. PMID- 29794282 TI - The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure? AB - BACKGROUND AND AIMS: The Numerical Rating Scale (NRS), Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), and Faces Pain Scale-Revised (FPS-R) are valid measures of pain intensity. However, ratings on these measures may be influenced by factors other than pain intensity. The purpose of this study was to evaluate the influence of non-pain intensity factors on the pain intensity scales. METHODS: We administered measures of pain intensity (NRS, VAS, VRS, FPS-R), pain unpleasantness, catastrophizing, depressive symptoms, and pain interference to 101 individuals with chronic lower back or knee pain. Correlation analyses examined the associations among the pain intensity scales, and regression analyses evaluated the contributions of the non-pain intensity factors (depressive symptoms, and pain unpleasantness, catastrophizing, and interference) to the VAS, VRS, and FPS-R ratings, while controlling for NRS, age, and gender. RESULTS: Although the NRS, VAS, VRS, FPR-S, scales were strongly associated with one another, supporting their validity as measures of pain intensity, regression analyses showed that the VRS also reflected pain interference, the FPS-R also reflected pain unpleasantness, and the VAS was not associated with any of the additional non-pain intensity factors when controlling for NRS, age, and gender. CONCLUSIONS: The VAS appears to be most similar to the NRS and less influenced by non-pain intensity factors than the VRS or FPS-R. Although the VRS and FPS-R ratings both reflect pain intensity, they also contain additional information about pain interference and pain unpleasantness, respectively. These findings should be kept in mind when selecting pain measures and interpreting the results of research studies using these scales. IMPLICATIONS: The influence of pain interference and pain unpleasantness on VRS and FPS-R, respectively should be kept in mind when selecting pain measures and interpreting the results of research studies using these scales. PMID- 29794283 TI - The MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain intensity in pregnant women. AB - BACKGROUND AND AIMS: Matrix metalloproteinase 9 (MMP9) is an enzyme that may affect degradation of several extracellular matrix (ECM) components in the pelvic ligaments during pregnancy. Previous studies indicate that genetic variations in the gene encoding MMP9 may affect the enzymatic activity. One such genetic variant is a single nucleotide polymorphism (SNP), rs17576 A>G. In this study we investigated whether the MMP9 SNP rs17576 A>G may be associated with increased lumbopelvic pain in 838 pregnant woman. The study was registered with ClinicalTrials.gov (NCT 00476567) on May 21, 2007. METHODS: Lumbopelvic pain intensity was measured by visual analog scale (VAS) at two time points during pregnancy, T1 (18-22 weeks), T2 (32-36 weeks) and 3 months after delivery. Blood samples were collected at each point and SNP genotyping was carried out using predesigned TaqMan SNP genotyping assays. RESULTS: The results showed a significant association between the number of G alleles and pain-intensity in the evening at T2. The pain among G/G carriers was higher than among A/G carriers, which in turn was higher than among the A/A carriers. The most pronounced association between the G allele and pain-intensity was observed in primiparae. CONCLUSIONS: We conclude that the MMP9 rs17576 A>G polymorphism is associated with increased lumbopelvic pain-intensity during pregnancy. The present data support the hypothesis that lumbopelvic pain during pregnancy may be related to a relaxin - MMP9 - tissue remodeling mechanism. IMPLICATIONS: The present findings may be important for future mechanistic studies on how MMP9 rs17576 A>G may affect changes in the ECM components in pelvic ligaments and lumbopelvic pain intensity during pregnancy. PMID- 29794284 TI - Pain, psychosocial tests, pain sensitization and laparoscopic pelvic surgery. AB - BACKGROUND AND AIMS: Individuals with non-acute pain are challenged with variable pain responses following surgery as well as psychological challenges, particularly depression and catastrophizing. The purpose of this study was to compare pre- and postoperative psychosocial tests and the associated presence of sensitization on a cohort of women undergoing elective laparoscopic surgery for non-acute pain defined as pain sufficient for surgical investigation without persistent of chronic pain. METHODS: The study was a secondary analysis of a previous report (Am J Obstet Gynecol 2014 Oct;211(4):360-8.). The study was a prospective cohort trial of 77 women; 61 with non-acute pain and 16 women for a tubal ligation. The women had the following tests: Pain Disability Index, Pain Catastrophizing Scale, CES-D (Center for Epidemiologic Studies Depression Scale) depression scale and the McGill Pain Scale (short form) as well as their average pain score and the presence of pain sensitization. All test scores were correlated together and comparisons were done using paired t-test. RESULTS: There were reductions in pain and psychosocial test scores that were significantly correlated. Pre-operative sensitization indicated greater changes in psychosocial tests. CONCLUSIONS: There was a close association of tests of psychosocial status with average pain among women having surgery on visceral tissues. Incorporation of these tests in the pre- and postoperative evaluation of women having laparoscopic surgery appears to provide a means to a broader understanding of the woman's pain experience. PMID- 29794285 TI - Mycophenolate for persistent complex regional pain syndrome, a parallel, open, randomised, proof of concept trial. AB - BACKGROUND AND AIMS: Current therapies for persistent complex regional pain syndrome (CRPS) are grossly inadequate. With accruing evidence to support an underlying immunological process and anecdotal evidence suggesting potential efficacy of mycophenolate, we wished to explore the feasibility and effectiveness of this treatment in patients with CRPS. METHODS: A randomised, open, parallel, proof of concept trial was conducted. Patients with Budapest research criteria CRPS of >2-year duration and moderate or high pain intensity (numeric rating scale score >=5) were enrolled. Eligible patients were randomised 1:1 to openly receive mycophenolate as add-on treatment, or their usual treatment alone, over 5.5 months. They then switched to the other treatment arm for 5.5 months. The main outcome was average the patients' average pain intensity recorded over 14 days, between 5.0 and 5.5 months post randomisation, on 11-point (0-10) numeric rating scales, compared between trial arms. Skin sensitivities and additional outcomes were also assessed. RESULTS: Twelve patients were enrolled. Nine provided outcomes and were analysed for the main outcome. Mycophenolate treatment was significantly more effective than control [drug-group mean (SD): pre: 7.4 (1.2)- post: 5.2 (1.3), n=4, control: pre: 7.7 (1.4)- post: 8.1 (0.9), n=5; -2.8 (95% CI: -4.7, -1.0), p=0.01, analysis of covariance]. There were four treatment responders (to mycophenolate treatment either before, or after switch), whose initial exquisite skin hyper-sensitivities, function and quality of life strongly improved. Side effects including itchiness, skin-cryptitis, increased pain, and increased depression caused 45% of the subjects to stop taking mycophenolate. CONCLUSIONS: Mycophenolate appears to reduce pain intensity and improve quality of life in a subgroup of patients with persistent CRPS. IMPLICATIONS: These results support the feasibility of conducting a definite trial to confirm the efficacy and effect size of mycophenolate treatment for persistent CRPS (EudraCT 2015-000263-14). PMID- 29794286 TI - What are the similarities and differences between healthy people with and without pain? AB - BACKGROUND AND AIMS: Knowledge of pain characteristics among the healthy population or among people with minimal pain-related disability could hold important insights to inform clinical practice and research. This study investigated pain prevalence among healthy individuals and compared psychosocial and physical characteristics between adults with and without pain. METHODS: Data were from 1,000 self-reported healthy participants aged 3-101 years (1,000 Norms Project). Single-item questions assessed recent bodily pain ("none" to "very severe") and chronic pain (pain every day for 3 months in the previous 6 months). Assessment of Quality of Life (AQoL) instrument, New Generalised Self-Efficacy Scale, International Physical Activity Questionnaire, 6-min walk test, 30-s chair stand and timed up-and-down stairs tests were compared between adults with and without pain. RESULTS: Seventy-two percent of adults and 49% of children had experienced recent pain, although most rated their pain as mild (80% and 87%, respectively). Adults with recent pain were more likely to be overweight/obese and report sleep difficulties, and had lower self-efficacy, AQoL mental super dimension scores and sit-to-stand performance, compared to adults with no pain (p<0.05). Effect sizes were modest (Cohen's d=0.16-0.39), therefore unlikely clinically significant. Chronic pain was reported by 15% of adults and 3% of children. Adults with chronic pain were older, more likely to be overweight/obese, and had lower AQoL mental super dimension scores, 6-min walk, sit-to-stand and stair-climbing performance (p<0.05). Again, effect sizes were modest (Cohen's d=0.25-0.40). CONCLUSIONS: Mild pain is common among healthy individuals. Adults who consider themselves healthy but experience pain (recent/chronic) display slightly lower mental health and physical performance, although these differences are unlikely clinically significant. IMPLICATIONS: These findings emphasise the importance of assessing pain-related disability in addition to prevalence when considering the disease burden of pain. Early assessment of broader health and lifestyle risk factors in clinical practice is emphasised. Avenues for future research include examination of whether lower mental health and physical performance represent risk factors for future pain and whether physical activity levels, sleep and self-efficacy are protective against chronic pain-related disability. PMID- 29794288 TI - Effects of activity interruptions by pain on pattern of activity performance - an experimental investigation. AB - BACKGROUND AND AIMS: Suspending an ongoing activity with the intention to resume it again later is a natural response to pain. This response facilitates coping with the pain, but it may also have negative consequences for the resumption and performance of the activity. For example, people with pain problems are often forced to take a break from doing their household chores because of their pain. They might delay resuming their chore, eventually needing longer time to finish it. We investigated how activity interruptions by pain influence the pattern of subsequent activity performance. We expected that when an activity is interrupted by pain (compared to non-pain), people spend longer time away from the activity, need longer time to complete it, and are less motivated to perform it. METHODS: Sixty healthy volunteers performed an ongoing task that required them to make joystick movements in different directions according to a specific rule. Occasionally, participants received either a painful electrocutaneous stimulus or a non-painful and non-aversive auditory stimulus (between-subjects) as an interruption cue. The interruption cue was followed by the temporary suspension of the ongoing task and the initiation of a different activity (interruption task). The latter required the categorization of cards and had a maximum duration, but participants could also stop it earlier by pressing a button. We measured time away from the (interrupted) ongoing task, total time to complete the ongoing task (including the interruptions) and self-reported motivation to perform both the ongoing as well as the interruption task. RESULTS: Groups did not differ in the time away from the ongoing task, total time to complete the ongoing task, or self-reported motivation to perform the two tasks. CONCLUSIONS: Activity interruptions by pain did not impair the pattern of activity performance more than activity interruptions by non-pain. Potential explanations and suggestions for future research are discussed. IMPLICATIONS: Interrupting ongoing activities is a common response to pain. However, activity interruptions by pain do not appear to influence the pattern of activity performance in a different way than activity interruptions by pain-irrelevant external stimuli. PMID- 29794287 TI - Cognitive behavioral therapy for irritable bowel syndrome: the effects on state and trait anxiety and the autonomic nervous system during induced rectal distensions - An uncontrolled trial. AB - BACKGROUND AND AIMS: Irritable bowel syndrome (IBS), is a common multifactorial gastrointestinal disorder linked to disturbances in the microbe gut-brain axis. Cognitive behavioral therapy (CBT), in face-to-face format has showed promising results on IBS and its associated psychological symptoms. The present study explored for the first time if CBT for IBS affects the autonomic nervous system (ANS) during experimentally induced visceral pain and cognitive stress, respectively. The levels of state and trait anxiety, current and perceived stress were also evaluated. METHODS: In this uncontrolled trial, individual CBT was performed in face-to-face format for 12 weeks in 18 subjects with IBS. Heart rate variability and skin conductance were measured during experimentally induced visceral pain and during a cognitive task (Stroop color-word test), before and after intervention. The levels of state and trait anxiety as well as self-rated current and perceived stress were also measured before and after the intervention. RESULTS: CBT did not affect ANS activity during experimentally induced visceral pain and cognitive stress. The sympathetic activity was high, typical for IBS and triggered during both visceral pain and cognitive stress. The levels of state and trait anxiety significantly decreased after the intervention. No significant changes in self-rated current or perceived stress were found. CONCLUSIONS: Results suggest that face-to-face CBT for IBS improved anxiety- a key psychological mechanism for the IBS pathophysiology, rather than the autonomic stress response to experimentally induced visceral pain and cognitive stress, respectively. IMPLICATIONS: This study indicates that IBS patients present high levels of stress and difficulties coping with anxiety and ANS activity during visceral pain and a cognitive stress test, respectively. These manifestations of IBS are however not targeted by CBT, and do not seem to be central for the study participants IBS symptoms according to the current and our previous study. Face-to-face CBT for IBS, it does not seem to affect modulation of ANS activity in response to induced visceral pain or cognitive stress. Instead, face-to-face CBT decreased levels of state and trait anxiety. Implications for further studies include that anxiety seems to be important in the IBS pathophysiology, and needs further scientific attention. This is in line with the fear-avoidance model which suggests that anxious responses to pain and discomfort drive hypervigilance to, and (behavioral) avoidance of, symptom provoking stimuli and vice versa. Catastrophic cognitions, hypervigilance and avoidant behavioral responses are proposed to produce vicious circles that withhold and exacerbate pain-related symptoms and disability, and lead to lower quality of life. Larger scale studies of potential autonomic changes are needed in order to elucidate which mechanisms elicit its effects in face-to-face CBT for IBS, and provide new avenues in understanding the pathophysiology of IBS. PMID- 29794289 TI - Psychosocial factors partially mediate the relationship between mechanical hyperalgesia and self-reported pain. AB - BACKGROUND AND AIMS: Amplification of sensory signalling within the nervous system along with psychosocial factors contributes to the variation and severity of knee pain. Quantitative sensory testing (QST) is a non-invasive test battery that assesses sensory perception of thermal, pressure, mechanical and vibration stimuli used in the assessment of pain. Psychosocial factors also have an important role in explaining the occurrence of pain. The aim was to determine whether QST measures were associated with self-reported pain, and whether those associations were mediated by psychosocial factors. METHODS: Participants with knee pain identified from a population-based cohort completed a tender point count and a reduced QST battery of thermal, mechanical and pressure pain thresholds, temporal summation, mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA) and vibration detection threshold performed following the protocol by the German Research Network on Neuropathic Pain. QST assessments were performed at the most painful knee and opposite forearm (if pain-free). Participants were asked to score for their global and knee pain intensities within the past month (range 0-10), and complete questionnaire items investigating anxiety, depression, illness perceptions, pain catastrophising, and physical functioning. QST measures (independent variable) significantly correlated (Spearman's rho) with self-reported pain intensity (dependent variable) were included in structural equation models with psychosocial factors (latent mediators). RESULTS: Seventy-two participants were recruited with 61 participants (36 women; median age 64 years) with complete data included in subsequent analyses. Tender point count was significantly correlated with global pain intensity. DMA at the knee and MPS at the most painful knee and opposite pain-free forearm were significantly correlated with both global pain and knee pain intensities. Psychosocial factors including pain catastrophising sub-scales (rumination and helplessness) and illness perceptions (consequences and concern) were significant partial mediators of the association with global pain intensity when loaded on to a latent mediator for: tender point count [75% total effect; 95% confidence interval (CI) 22%, 100%]; MPS at the knee (49%; 12%, 86%); and DMA at the knee (63%; 5%, 100%). Latent psychosocial factors were also significant partial mediators of the association between pain intensity at the tested knee with MPS at the knee (30%; 2%, 58%), but not for DMA at the knee. CONCLUSIONS: Measures of mechanical hyperalgesia at the most painful knee and pain-free opposite forearm were associated with increased knee and global pain indicative of altered central processing. Psychosocial factors were significant partial mediators, highlighting the importance of the central integration of emotional processing in pain perception. IMPLICATIONS: Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain. PMID- 29794290 TI - Efficacy and safety of epidural, continuous perineural infusion and adjuvant analgesics for acute postoperative pain after major limb amputation - a systematic review. AB - BACKGROUND AND AIMS: Treatment of pain following major limb amputations is often a clinical challenge in a patient population consisting mainly of elderly with underlying diseases. Literature on management of acute post-amputation pain is scarce. We performed a systematic review on this topic to evaluate the efficacy and safety of analgesic interventions for acute pain following major limb amputation. METHODS: A literature search was performed in PubMed, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews using the following key words: [(amputation) AND (pain OR analgesi* OR pain relief)] AND (acute OR postoperative). Randomized controlled studies (RCTs) and observational studies investigating treatment of acute pain following major amputations for any indication (peripheral vascular disease, malignant disease, trauma) were included. The review was performed according to the standards described in the PRISMA statement. The Cochrane quality assessment tool was used to evaluate the risk of bias in the RCTs. RESULTS: Nineteen studies with total of 949 patients were included. The studies were generally small and heterogeneous on outcomes, study designs and quality. There were 16 studies on epidural or continuous perineural analgesia (CPI). Based on five RCTs (n=268) and two observational studies (n=49), epidural analgesia decreased the intensity of acute stump pain as compared to systemic analgesics, during the first 24 h after the operation. Based on one study epidural analgesia caused more adverse effects like sedation, nausea and motor block than continuous perineural local anesthetic infusion. Based on one RCT (n=21) and eight observational studies (n=501) CPI seemed to decrease opioid consumption as compared to systemic analgesics only, on the first three postoperative days, and was well tolerated. Only three trials investigated systemic analgesics (oral memantine, oral gabapentine, iv ketamine). Ketamine did not decrease acute pain or opioid consumption after amputation as compared to other systemic analgesics. Gabapentin did not decrease acute pain when combined to epidural analgesia as compared to epidural analgesia and opioid treatment, and caused adverse effects. CONCLUSIONS: The main finding of this systematic review is that evidence regarding pain management after major limb amputation is very limited. Epidural analgesia may be effective, but firm evidence is lacking. Epidural causes more adverse effects than CPI. The results on efficacy of CPI are indecisive. The data on adjuvant medications combined to epidural analgesia or CPI is limited. Studies on efficacy and adverse effects of systemic analgesics for amputation pain, especially concentrating on elderly patients, are needed. PMID- 29794291 TI - Pain, psychological distress and motor pattern in women with provoked vestibulodynia (PVD) - symptom characteristics and therapy suggestions. AB - BACKGROUND AND AIMS: Provoked vestibulodynia (PVD) represent a longstanding pain syndrome that affects large numbers of women worldwide. However, no standardized guidelines for PVD treatment exist. In a cross-sectional pilot study we examined 30 PVD patients on multidimensional parameters including pain, psychological distress and quality of movement, in order to obtain a broader understanding of the somatic and psychological symptoms in PVD, and for the future to develop better interventions. Additionally, we compare the findings to previously published results regarding the same parameters in women with chronic pelvic pain (CPP). METHODS: Thirty women with PVD recruited from a tertiary care university clinic of gynecology were assessed for demographic data, pain intensity (VAS), psychological distress (GHQ-30 and Tampa scale of Kinesophobia) and quality of movement (standardized Mensendieck test, SMT). RESULTS: Average age of the PVD women was 24.7+/-3.60 years, 60% of them were in permanent relationships, all were nulliparous, none had been subjected to surgical procedures, 100% were working full or part time and 90% were educated to at least undergraduate level. Mean VAS score was 7.77+/-1.97 (mean+/-SD), kinesiophobia 24.4+/-3.95 and anxiety domain of GHQ-30 9.73+/-4.06. SMT scores were particularly low for the domains of respiration and gait (less than 50% of optimal scores). CONCLUSIONS: PVD women display reduced quality of movement, especially for gait and respiration patterns, increased level of anxiety and high average pain scores. These findings are similar to what we have previously reported in CPP patients. However, in contrast to CPP group, PVD women are on average younger, have higher work participation, higher education level and have not been subjected to surgical procedures. IMPLICATIONS: Since PVD women display similar, although somewhat less severe, symptom profile than CPP, we suggest that a multidimensional approach to treatment, such as "somatocognitive therapy" should be investigated in this group as it has previously been shown to be promising in treatment of CPP. PMID- 29794292 TI - The Standardised Mensendieck Test as a tool for evaluation of movement quality in patients with nonspecific chronic low back pain. AB - BACKGROUND AND AIMS: Nonspecific chronic low back pain is a multifactorial biopsychosocial health problem where accurate assessments of pain, function and movement are vital. There are few reliable and valid assessment tools evaluating movement quality, hence the aim was to investigate nonspecific chronic low back pain patients' movement patterns with the Standardised Mensendieck Test. METHODS: Twenty patients (mean age=41, SD=9.02) with nonspecific chronic low back pain were examined with the Standardised Mensendieck Test whilst being videotaped and compared with 20 healthy controls. A physiotherapist, blinded to participant's group belonging, scored Standardised Mensendieck Test videos according to the standardised manual. Associations between movement quality, fear of movement and re(injury) i.e. kinesiophobia and pain intensity were also investigated. RESULTS: Patients scored significantly poorer than the controls in all 5 Standardised Mensendieck Test domains (p<0.001). The biggest difference was observed with regard to movement pattern domain. In women we also found a difference in the respiration pattern domain. CONCLUSIONS: The Standardised Mensendieck Test was able to detect significant differences in quality of movement between patients and healthy controls. These results indicate that the Standardised Mensendieck Test may be a valuable examination tool in assessment and treatment of nonspecific chronic low back pain patients. Further, longitudinal studies should investigate whether poor movement and respiration patterns are important factors in nonspecific chronic low back pain, e.g. as predictors and/or mediators of therapeutic effects. PMID- 29794293 TI - Relative and absolute test-retest reliabilities of pressure pain threshold in patients with knee osteoarthritis. AB - BACKGROUND AND AIMS: Pressure pain threshold (PPT) and PPT maps are commonly used to quantify and visualize mechanical pain sensitivity. Although PPT's have frequently been reported from patients with knee osteoarthritis (KOA), the absolute and relative reliability of PPT assessments remain to be determined. Thus, the purpose of this study was to evaluate the test-retest relative and absolute reliability of PPT in KOA. For that purpose, intra- and interclass correlation coefficient (ICC) as well as the standard error of measurement (SEM) and the minimal detectable change (MDC) values within eight anatomical locations covering the most painful knee of KOA patients was measured. METHODS: Twenty KOA patients participated in two sessions with a period of 2 weeks+/-3 days apart. PPT's were assessed over eight anatomical locations covering the knee and two remote locations over tibialis anterior and brachioradialis. The patients rated their maximum pain intensity during the past 24 h and prior to the recordings on a visual analog scale (VAS), and completed The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and PainDetect surveys. The ICC, SEM and MDC between the sessions were assessed. The ICC for the individual variability was expressed with coefficient of variance (CV). Bland-Altman plots were used to assess potential bias in the dataset. RESULTS: The ICC ranged from 0.85 to 0.96 for all the anatomical locations which is considered "almost perfect". CV was lowest in session 1 and ranged from 44.2 to 57.6%. SEM for comparison ranged between 34 and 71 kPa and MDC ranged between 93 and 197 kPa with a mean PPT ranged from 273.5 to 367.7 kPa in session 1 and 268.1-331.3 kPa in session 2. The analysis of Bland-Altman plot showed no systematic bias. PPT maps showed that the patients had lower thresholds in session 2, but no significant difference was observed for the comparison between the sessions for PPT or VAS. No correlations were seen between PainDetect and PPT and PainDetect and WOMAC. CONCLUSIONS: Almost perfect relative and absolute reliabilities were found for the assessment of PPT's for KOA patients. IMPLICATIONS: The present investigation implicates that PPT's is reliable for assessing pain sensitivity and sensitization in KOA patients. PMID- 29794294 TI - Postural control in subclinical neck pain: a comparative study on the effect of pain and measurement procedures. AB - BACKGROUND AND AIMS: This study investigated whether young university students with neck pain (NP) have postural control deficits when compared to sex and age matched asymptomatic subjects. METHODS: Centre of pressure (COP) sway area, velocity, anterior-posterior and mediolateral distances were measured in participants with (n=27) and without (n=27) neck pain for different combinations of static standing (narrow stance, tandem stance and single leg stance) and measurement time (90, 60, 30 and 15 s) with eyes closed using a force plate. Additionally, static and dynamic clinical tests of postural control were used. RESULTS: No significant between group differences were found for the COP measurements (p>0.05). However, individuals with subclinical NP were more likely to fail the 90 s tandem test (p<0.05) in the force plate and univariate comparisons revealed significant between group differences in the tandem and single leg stance clinical test measurements. CONCLUSIONS: Taken together, the inconsistent results might suggest an emerging postural control deficit in university students with low disability and low intensity chronic idiopathic NP. PMID- 29794295 TI - Chronic pain experience and pain management in persons with spinal cord injury in Nepal. AB - BACKGROUND AND AIMS: Chronic pain is the frequent and significantly challenging complications in persons with spinal cord injury (SCI). Socio-cultural background may lead people perceive and manage pain differently. The study aims to describe the chronic pain experience and pain management of SCI persons in Nepal. METHODS: A descriptive cross sectional study was conducted among purposively selected sample of 120 SCI persons with chronic pain living in the eight districts of Bagmati Zone of Nepal. The data were collected using the International Spinal Cord Injury Pain Basic Data Set Version 2 (ISCIPBDS-2) and Open-ended Pain Management Questionnaire. The data were analyzed using descriptive statistics and content analysis method. RESULTS: The back (n=84), lower legs/feet (n=63) and buttocks/hips (n=51) was found as the common pain locations. In common, the onset of pain was found within the first 6 month of the injury. Overall pain intensity and pain interference were found to be at the moderate level. The SCI persons used pain medications and non-pharmacological pain management. Ibuprofen was the commonly used pain medication and commonly used non-pharmacological pain management methods included physical support (e.g. massage, exercise), relaxation (e.g. distraction, substance abuse), coping (e.g. acceptance, praying), and traditional herbs. CONCLUSIONS: SCI persons had chronic pain experience which interfered with their daily living. They used pain medications and non pharmacological pain management methods based on their beliefs, knowledge, and community resources in Nepal. IMPLICATIONS: This study provides some evidence to help the team of rehabilitation professional to plan and help SCI persons with chronic pain. Based on these findings, chronic pain management intervention for SCI persons should be developed and supported continuously from hospital to home based community context of Nepal. PMID- 29794296 TI - The influence of pre- and perioperative administration of gabapentin on pain 3-4 years after total knee arthroplasty. AB - BACKGROUND AND AIMS: Approximately 20% of patients having total knee arthroplasty (TKA) will experience chronic postoperative pain. Recently, preoperative pain facilitation has been associated with chronic pain after TKA, and gabapentin has been shown to decrease pain facilitation. The current study is a secondary follow up of a primary RCT investigating the effect of gabapentin on acute postoperative pain after TKA and exploring the effect of pre- and perioperative administration of gabapentin on chronic postoperative pain and psychological state 3-4 years after TKA. METHODS: Patients scheduled for TKA were randomized to either gabapentin 1,300 mg/day, gabapentin 900 mg/day, or placebo daily from 2-h before and 6 days after operation. Pre- and 3-4 years postoperatively pain scores related to pain while walking, at rest, when flexing the hip or the knee were collected. At the same time, the pain catastrophizing scale (PCS) and hospital anxiety and depression scale subscales for anxiety (HADS-A) and depression (HADS D) were collected. RESULTS: Lower postoperative pain while walking, flexing the hip, and at rest were found compared with preoperative scores (p<0.03), but these were not associated with gabapentin treatment (p>0.19). Significantly lower postoperative PCS and HADS-A scores were seen compared with preoperative scores (p<0.001), but these were not associated with gabapentin treatment (p>0.55). CONCLUSIONS: The current study found that pre- and perioperative administrations of gabapentin do not influence the pain or psychological state 3-4 years after TKA. IMPLICATIONS: The current study does not support that short-term pre- and perioperative use of gabapentin can reduce the development of chronic postoperative pain after TKA. PMID- 29794297 TI - Prevalence of self-reported musculoskeletal pain symptoms among school-age adolescents: age and sex differences. AB - BACKGROUND AND AIMS: Non-specific musculoskeletal pain symptoms are common in adolescents and may differ between the sexes, and be related to age and daily activities. It is critical to examine the prevalence and frequency of symptoms in adolescent students who tend to have pain which interferes with their routine activities. This study aimed to explore the prevalence and frequency of self reported musculoskeletal pain symptoms by age and sex, and we also examined the association of symptoms with routine activities of school-age adolescents by area of pain. METHODS: A cross-sectional survey was conducted among Thai students aged 10-19 years. All 2,750 students were asked to report previous 7-day and/or 12 month pain using the Standardized Nordic Questionnaire (Thai version) in 10 body areas. Multivariable logistic regression adjusted for age and sex was used to analyze the association between daily activity and musculoskeletal pain symptoms. RESULTS: A total of 76.1% (n=2,093) of students reported experiencing pain in the previous 7 days, 73.0% (n=2,007) reported in the previous 12-month period and 83.8% (n=2,304) reported pain in both 7-day and 12-month periods. The most common pain area was from a headache, with other areas being neck and shoulders, in that order, for both periods of time. The prevalence of musculoskeletal pain was especially higher in older groups and females. Participants reported frequency of pain as "sometimes in different areas" ranging from 78.4% to 88% and severity of pain at 3.82+/-2.06 out of 10 (95% CI 3.74-3.91). Routine daily activities associated with symptoms of headache, neck, shoulders, and ankles or feet pain were computer use (head, OR=2.22), school bag carrying (neck, OR=2.05), school bag carrying (shoulder, OR=3.09), and playing sports (ankle or foot, OR=2.68). CONCLUSIONS: The prevalence of musculoskeletal pain symptoms was high in both the previous 7-day and 12-month periods, especially in females and older adolescents, although most of them sometimes experienced pain. Computer use and school bag carrying were associated with headache, neck and shoulder pain, while playing sports was related to symptoms of the foot and ankle. IMPLICATIONS: The prevalence of pain was high, particularly in the older and female groups. Although they experienced mild symptoms sometimes, the related daily activities leading to these symptoms should be closely noticed. PMID- 29794298 TI - Exercise does not produce hypoalgesia when performed immediately after a painful stimulus. AB - BACKGROUND AND AIMS: Exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) are assumed to reflect descending pain inhibition. Potential interactions between EIH and CPM may be important in the therapy of chronic pain, as reduced CPM and increased pain after exercise are frequently observed. This study compared the EIH response after CPM was activated using a cold pressor task with the EIH response after a control condition. METHODS: Thirty-one participants (age: 27.7+/-9.8; 15 female) completed two sessions: a cold pressor task (CPT) session, i.e. testing EIH with preceding CPM activation induced using a 2 min CPT at approximately 2 degrees C, and a control session, i.e. testing EIH after a control condition (2 min of quiet rest). EIH was induced using a 15 min bicycling exercise at a target heart rate corresponding to 75% VO2 max. Repeated measures ANOVAs on pressure pain thresholds (PPTs) at the hand, back and leg were used to determine the effects of exercise after the cold pressor test and control condition. Furthermore, correlations between CPM and EIH, in the CPT session as well as control session, were calculated at each assessment site. RESULTS: A significant time x condition interaction (F(1, 30)=43.61, p<0.001, partial eta2=0.59), with Bonferroni-corrected post-hoc t-tests showed that PPTs increased after exercise in the control session (p<0.001), but not in the CPT session (p=0.125). Furthermore, there was a small positive correlation of EIH in the control session and CPM at the hand (r=0.37, p=0.043). There was a moderate negative correlation of EIH in the CPT session and CPM at the hand (r=-0.50, p=0.004), and smaller negative correlations at the back (r=-0.37, p=0.036) and at the leg (r=-0.35, p=0.054). CONCLUSIONS: Attenuated EIH after the CPM activation in comparison to a control condition suggests that EIH and CPM may share underlying pain inhibitory mechanisms on a systemic level. This assumption is further supported by the finding of small to moderate significant correlations between EIH and CPM at the hand. The attenuated EIH response furthermore suggests that these mechanisms are exhaustible, i.e. that its effects decline after a certain amount of inhibition. IMPLICATIONS: In patients with chronic pain, assessing the current capacity of the descending pain inhibitory system - as indicated by the CPM response - may aid to make better predictions about how patients will respond to exercise with respect to acute pain reduction. PMID- 29794299 TI - Reliability of three linguistically and culturally validated pain assessment tools for sedated ICU patients by ICU nurses in Finland. AB - BACKGROUND AND AIMS: Pain assessment in intensive care is challenging, especially when the patients are sedated. Sedated patients who cannot communicate verbally are at risk of suffering from pain that remains unnoticed without careful pain assessment. Some tools have been developed for use with sedated patients. The Behavioral Pain Scale (BPS), the Critical-Care Pain Observation Tool (CPOT) and the Nonverbal Adult Pain Assessment Scale (NVPS) have shown promising psychometric qualities. We translated and culturally adapted these three tools for the Finnish intensive care environment. The objective of this feasibility study was to test the reliability of the three pain assessment tools translated into Finnish for use with sedated intensive care patients. METHODS: Six sedated intensive care patients were videorecorded while they underwent two procedures: an endotracheal suctioning was the nociceptive procedure, and the non-nociceptive treatment was creaming of the feet. Eight experts assessed the patients' pain by observing video recordings. They assessed the pain using four instruments: the BPS, the CPOT and the NVPS, and the Numeric Rating Scale (NRS) served as a control instrument. Each expert assessed the patients' pain at five measurement points: (1) right before the procedure, (2) during the endotracheal suctioning, (3) during rest (4) during the creaming of the feet, and (5) after 20 min of rest. Internal consistency and inter-rater reliability of the tools were evaluated. After 6 months, the video recordings were evaluated for testing the test-retest reliability. RESULTS: Using the BPS, the CPOT, the NVPS and the NRS, 960 assessments were obtained. Internal consistency with Cronbach's alpha coefficient varied greatly with all the instruments. The lowest values were seen at those measurement points where the pain scores were 0. The highest scores were achieved after the endotracheal suctioning at rest: for the BPS, the score was 0.86; for the CPOT, 0.96; and for the NVPS, 0.90. The inter-rater reliability using the Shrout-Fleiss intraclass correlation coefficient (ICC) tests showed the best results after the painful procedure and during the creaming. The scores were slightly lower for the BPS compared to the CPOT and the NVPS. The test-retest results using the Bland-Altman plots show that all instruments gave similar results. CONCLUSIONS: To our knowledge, this is the first time all three behavioral pain assessment tools have been evaluated in the same study in a language other than English or French. All three tools had good internal consistency, but it was better for the CPOT and the NVPS compared to the BPS. The inter-rater reliability was best for the NVPS. The test-retest reliability was strongest for the CPOT. The three tools proved to be reliable for further testing in clinical use. IMPLICATIONS: There is a need for feasible, valid and reliable pain assessment tools for pain assessment of sedated ICU patients in Finland. This was the first time the psychometric properties of these tools were tested in Finnish use. Based on the results, all three instruments could be tested further in clinical use for sedated ICU patients in Finland. PMID- 29794300 TI - CT guided neurolytic blockade of the coeliac plexus in patients with advanced and intractably painful pancreatic cancer. AB - BACKGROUND AND AIMS: Pain caused by infiltrating pancreatic cancer is complex in nature and may therefore be difficult to treat. In addition to conventional analgesics, neurolytic blockade of the coeliac plexus is often recommended. However, different techniques are advocated, and procedures vary, and the results may therefore be difficult to compare. Therefore strong evidence for the effect of this treatment is still lacking, and more studies are encouraged. Our aim was to describe our technique and procedures using a Computer Tomograph (CT) guided procedure with a dorsal approach and present the results. METHODS: The procedures were performed in collaboration between a radiologist and an anaesthesiologist. All patients had advanced pancreatic cancer. The patients were placed in prone position on pillows, awake and monitored. Optimal placement of injection needles was guided by CT, and the radiologist injected a small dose of contrast as a control. When optimal needle position, the anaesthesiologist took over and completed the procedure. At first 40 mg methylprednisolone was injected to prevent inflammation. Thereafter a mixture of 99% ethanol diluted to 50% by ropivacaine 7.5 mg/mL to a total amount of 20-30 mL per needle was slowly injected. Repeated aspiration was performed during injection to avoid intravasal injection. Pain treatment and pain score was recorded and compared before and after the treatment. RESULTS: Eleven procedures in 10 patients were performed. Age 49-75, mean 59 years. Median rest life time was 36 days (11-140). Significant reduction of analgesics was observed 1 week after the procedure, and most patients also reported reduction of pain. No serious side effects were observed. CONCLUSIONS: CT guided neurolytic celiac plexus blockade is a safe and effective treatment for intractable pain caused by advanced pancreatic cancer. Not all patients experience a significant effect, but the side effects are minor, and the procedure should therefore be offered patients experiencing intractable cancer related pain. PMID- 29794301 TI - Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome. AB - BACKGROUND AND AIMS: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. METHODS: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. RESULTS: CWP was associated with higher cortisol (464+/-141 vs. 366+/-111 nmol/L, p=0.011) and fasting glucose (6.0+/-0.8 vs. 5.4+/-0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (beta=122+/-47 nmol/L and 0.89+/-0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35+/-22 vs. 21+/-34 min, p=0.022), and pulse wave attenuation was more frequent (11+/-8 vs. 6+/-2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (beta=3.1+/-1.3, p=0.018). CONCLUSIONS: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. IMPLICATIONS: CWP is associated with activated stress markers that may deteriorate sleep. PMID- 29794302 TI - Exploring effect of pain education on chronic pain patients' expectation of recovery and pain intensity. AB - BACKGROUND AND AIMS: Chronic pain affects an estimated 1 in 10 adults globally regardless of age, gender, ethnicity, income or geography. Chronic pain, a multifactorial problem requires multiple interventions. One intervention which demonstrates promising results to patient reported outcomes is pain education. However, patient perspective on pain education and its impact remains fairly unknown. A cross-sectional study involving individuals with chronic pain examined their perspectives on pain education; did it change their understanding about their pain and self-management and did it have any impact on their perceived pain intensity and recovery. METHODS: The study complied with CHERRIES guidelines and the protocol was locked prior to data collection. Primary outcomes were pain intensity and participants' expectation of recovery. Univariate and multiple logistic regressions were used to analyze the data. RESULTS: Five hundred and seventy three people participated; full data sets were available for 465. Participants who observed changes in their pain cognition and self-management following pain education reported lower pain intensity and greater expectation of recovery than participants who did not observe changes to cognition and management. CONCLUSIONS: The results suggest that individuals who observed changes to pain cognition and self-management on receiving pain education reported lower pain intensity and higher expectations of recovery than their counterparts who did not perceive any changes to pain cognition and self management. IMPLICATIONS: Pain intensity and expectations about recovery are primary considerations for people in pain. What influences these factors is not fully understood, but education about pain is potentially important. The results suggest that individuals who observed changes to pain cognition and self management on receiving pain education reported lower pain intensity and higher expectations of recovery than their counterparts who did not perceive any changes to pain cognition and self-management. The results from this study highlight the importance of effective pain education focused on reconceptualization of pain and its management. PMID- 29794303 TI - Prescription of opioids to post-operative orthopaedic patients at time of discharge from hospital: a prospective observational study. AB - BACKGROUND AND AIMS: Excessive opioid prescribing can lead to adverse consequences including stockpiling, misuse, dependency, diversion and mortality. Increased prescriptions to post-operative inpatients as part of their discharge planning may be a significant contributor. Primary aims included comparing the amount of opioids prescribed, consumed, left unused and their relationship with pain and functionality. METHODS: A total of 132 consecutive patients who underwent elective orthopaedic surgery were prospectively audited. Daily oral morphine equivalent (DME) of opioids prescribed was compared with opioids consumed and amount left unused 7-10 days after discharge. For analysis, patients were split into three groups: total knee replacement (TKR), hand surgery (Hands), and miscellaneous (Misc). RESULTS: The mean dose of opioid prescribed per patient was 108.5 mg DME. TKR consumed 33-35% more opioids than Misc (p=0.0283) and Hands (p=0.0975). Age was a significant independent factor for opioid consumption in the 50th and 75th percentiles of Hands (p<=0.05). An average of 36 mg DME per patient was left unused with Hands having the highest median DME (37 mg) unused. In the total cohort, 26% of patients were discharged with more DME than their last 24 h as an inpatient and had at least 50% of their tablets left unused at follow-up. CONCLUSIONS: Over-prescription of opioids occurs at discharge which can increase the risk of harm. New intervention is needed to optimise prescribing practises. IMPLICATIONS: Changes to prescribing habits and workplace culture are required to minimise unnecessary opioid prescribing but will be challenging to implement. A multi-layered approach of electronic prescribing, opioid stewardship and targeted educational awareness programmes is recommended. PMID- 29794304 TI - Exercise-induced hypoalgesia in women with varying levels of menstrual pain. AB - BACKGROUND AND AIMS: Exercise-induced hypoalgesia (EIH) is a well-established phenomenon in pain-free individuals that describes a decrease in pain sensitivity after an acute bout of exercise. The EIH response has been demonstrated to be sub optimal in the presence of persisting pain. Menstrual pain is a common recurrent painful problem with many women experiencing high levels of pain each cycle. However, the EIH response has not been examined in a cohort of women with high levels of menstrual pain. This research aimed to examine whether EIH manifests differently in women with varying levels of menstrual pain. The primary hypothesis was that women with high levels of menstrual pain would demonstrate compromised EIH. Secondary aims were to explore relationships between EIH and emotional state, sleep quality, body mass index (BMI) or physical activity levels. METHODS: Pressure pain thresholds (PPT) were measured in 64 participants using a digital handheld algometer before and after a submaximal isometric handgrip exercise. EIH index was compared between low (VAS 0-3), moderate (VAS 4 7) and high (VAS 8-10) pain groups, using a linear mixed model analysis with participant as a random effect, and site, menstrual pain category and the interaction between the two, as fixed effects. RESULTS: EIH was consistently induced in all groups. However, there was no statistically significant difference between the pain groups for EIH index (p=0.835) or for any co-variates (p>0.05). CONCLUSIONS: EIH was not found to differ between women who report regular low, moderate or high levels of menstrual pain, when measured at a point in their menstrual cycle when they are pain free. IMPLICATIONS: This study provides insight that EIH does not vary in women with differing levels of menstrual pain when they are not currently experiencing pain. The current findings indicate that, although menstrual pain can involve regular episodes of high pain levels, it may not be associated with the same central nervous system dysfunctions as seen in sustained chronic pain conditions. PMID- 29794305 TI - Effectiveness of neck stabilisation and dynamic exercises on pain intensity, depression and anxiety among patients with non-specific neck pain: a randomised controlled trial. AB - BACKGROUND AND AIMS: Non-specific neck pain (NsNP) constitutes a burden to the bearers and a management challenge to physiotherapists globally. Effectiveness of neck stabilisation and dynamic exercises in the management of NsNP has been documented, but it is not clear which exercise regimen is more effective in alleviating its associated pain, depression and anxiety. This study was carried out to compare the effectiveness of neck stabilisation and/or dynamic exercises on pain intensity, depression and anxiety among patients with NsNP. METHODS: Eighty-nine consenting individuals with NsNP participated in this single-blind, randomised controlled trial. They were recruited from the outpatient physiotherapy clinics of the National Orthopaedic Hospital in Dala, Kano State, Nigeria. Participants were randomly assigned into one of three intervention groups: neck stabilisation exercise group (NSEG; n=30), neck dynamic exercise group (NDEG; n=28) and neck stabilisation and dynamic exercise group (NSDEG; n=31). Treatment was administered thrice weekly for 8 consecutive weeks. Variables were assessed at baseline, at the end of the fourth and eighth weeks. Pain intensity was assessed through the use of a visual analogue scale, while depression and anxiety were evaluated using both the Beck Depression Inventory and Beck Anxiety Inventory. The data was analysed using descriptive statistics, multivariate analysis of variance (MANOVA) and post hoc tests with Bonferroni adjustment at the p=0.05 significant level. RESULTS: Ages of participants in NSEG (46.8+/-12.4 years), NDEG (48.6+/-11.6 years) and NSDEG (45.1+/-13.4 years) were comparable. The comparison for NSEG, NSDEG and NDEG within groups revealed that there was significant difference in pain intensity, depression and anxiety scores from baseline, in the fourth and eighth weeks of the study - (F=62.40, p=0.001, F=13.91, p=0.001 and F=20.93, p=0.001); (F=11.92, p=0.001, F=8.75, p=0.004 and F=9.70, p=0.001) and (F=36.63, p=0.001, F=11.99, p=0.001 and F=6.59, p=0.001), respectively. A group comparison of the pain intensity, depression and anxiety scores of participants in the NSEG, NSDEG and NDEG at the baseline of the study revealed that there were no significant differences in the pain intensity and depression and anxiety scores among the three groups: p=0.159, 0.58 and 0.179, respectively. At week 4 of the study, however, a significant difference in pain intensity and anxiety scores across the three groups was recorded - p=0.018, p=0.011, respectively, but no significant difference was noted in depression scores (p=0.93). At week 8 of the study, it was determined that there were significant differences in pain intensity and depression scores p=0.001 and p=0.041, but no significant dissimilarities in the anxiety scores. Post hoc revealed that only pain was significant and lay with NSEG. CONCLUSIONS: The study concluded that the stabilisation, dynamic and stabilisation, plus dynamic exercises were effective in relieving pain and reducing depression and anxiety in patients with NsNP. However, stabilisation showed a more marked effect than the combination exercises of stabilisation plus dynamic exercises, and dynamic exercises in reducing pain intensity in patients with NsNP. IMPLICATIONS: It is recommended that stabilisation exercises be chosen over stabilisation plus dynamic exercises, or dynamic exercise, while treating patients with NsNP. However, both are effective. PMID- 29794306 TI - A multiple-dose double-blind randomized study to evaluate the safety, pharmacokinetics, pharmacodynamics and analgesic efficacy of the TRPV1 antagonist JNJ-39439335 (mavatrep). AB - BACKGROUND AND AIMS: This double-blind (DB), randomized, placebo-controlled, sequential-group, multiple-ascending dose, phase 1 study evaluated safety, pharmacokinetics and pharmacodynamics of JNJ-39439335 in healthy men (part 1), and in participants with knee osteoarthritis (part 2). METHODS: Both parts 1 and 2 consisted of screening (upto 21 days), 21-day DB treatment phase [eight participants/group: JNJ-39439335 (part 1: 2-50 mg; part 2: 10-50 mg): n=6; placebo: n=2] and follow-up (total study duration ~10 weeks). RESULTS: Plasma concentrations and systemic exposure of JNJ-39439335 increased in slightly higher than dose-proportional fashion (steady-state reached by day 14). Renal excretion of JNJ-39439335 was negligible. Marked dose-related increases in pharmacodynamic heat pain assessments were observed in JNJ-39439335-treated participants, which persisted throughout the treatment with no signs of tolerance with repeated dosing. No effect on pharmacodynamic cold pain or mechanical pain assessments were seen. Effects on pharmacodynamic capsaicin-induced flare assessments in JNJ 39439335-treated participants versus placebo were consistent with effects observed with single-dose, and did not demonstrate tolerance with multiple dosing. In participants with knee osteoarthritis, significant improvements versus placebo were observed in a stair-climbing-induced pain model. All JNJ-39439335 treated participants reported >=1 treatment-emergent adverse events (TEAE); most common (>=50% incidence) TEAEs in part 1 were feeling hot (79%), thermohypoesthesia (71%), paresthesia (58%) and feeling cold (50%), and in part 2, were minor thermal burns (50%). CONCLUSIONS: JNJ-39439335 (doses 2-50 mg) was well-tolerated, and associated with acceptable multiple-dose pharmacokinetic profile. JNJ-39439335 demonstrated sustained pharmacodynamic effects (heat pain perception, heat pain latency, capsaicin-induced flare), and an efficacy signal in participants with osteoarthritis pain. IMPLICATIONS: Given the efficacy signal observed and the unique safety profile, larger phase 2 studies are needed to better understand the potential of JNJ-39439335 in the treatment of chronic pain. Analgesic efficacy of lower doses administered over a longer period of time and improved patient counseling techniques to reduce the minor thermal burns can be explored to minimize the adverse events. PMID- 29794307 TI - The psychological features of patellofemoral pain: a cross-sectional study. AB - BACKGROUND AND AIMS: Patellofemoral pain (PFP) is a prevalent and debilitating musculoskeletal condition, considered to have a mechanical aetiology. As such, the physical impairments associated with PFP are well documented and have helped characterise different physical phenotypes. But little is known about the relationship between PFP and psychological well-being. In this study, we aimed to: (1) compare psychological profiles between groups with and without PFP; (2) compare psychological profiles and condition severity between PFP subgroups; and (3) explore relationships between psychological factors and their contribution to disability. We expected to find higher levels of psychological impairment, especially kinesiophobia and catastrophizing in the PFP group. We also expected to identify a sub-group for who worsening levels of disability correspond with worsening psychological well-being. METHODS: One hundred participants with PFP (72 females, mean+/-SD age 27+/-5 years, BMI 25.3+/-4.8 kg/m2) completed measures of pain, disability, and psychological features (kinesiophobia, catastrophizing, anxiety and depression). Fifty controls, matched by sex, age and activity level (36 females, age 27+/-5 years, BMI 22.9+/-4.5 kg/m2) also completed psychological measures. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to cluster PFP participants (K-means cluster analysis) into more and less severe sub groups. Differences between the control and PFP groups were analysed using t tests, analysis of variance, Mann-Whitney U-tests or chi2 tests as appropriate (p<0.05). Pearson correlations were used to explore relationships between psychological measures. Backward stepwise regression (p out >0.05) evaluated how the psychological factors potentially relate to disability. RESULTS: Psychological features did not differ between PFP and pain-free groups. But differences were apparent when the PFP cohort was subgrouped. Compared to controls, the more-severe group had significantly higher levels of depression (MD 1.8, 95% CI 0.8-2.8; p<=0.001) and catastrophizing (MD 5.7, 95% CI 2.4-9; p<=0.001). When compared to less-severe cases, the more-severe group also demonstrated significantly higher levels of kinesiophobia (MD 4.3, 95% CI 2.1 6.5; p<=0.001), depression (MD 1.5 95% CI 0.5-2.6; p=0.01) and catastrophizing (MD 4.9, 95% CI 1-8.8; p=0.01). The weakest relationship between psychological factors was found between kinesiophobia and anxiety (r=0.29; p=0.02). While the strongest relationship existed between depression and anxiety (r=0.52; p<=0.001). Both kinesiophobia (beta -0.27, 95% CI -0.265 to -0.274) and depression (beta 0.22, 95% CI -0.211 to -0.228) were associated with disability as defined by the KOOS in the regression model (R2=0.17, p<=0.001). CONCLUSIONS: Those with more severe PFP-related disability have higher levels of psychological impairment than less-severe cases. Kinesiophobia seems to stand as an important factor in the experience of PFP, because it was elevated in the PFP group, significantly differed between the PFP sub-groups and contributed to explaining disability. Contrary to our hypothesis, levels of catastrophizing in the PFP group and severe sub-group were low and seemingly not important. IMPLICATIONS: These findings draw attention to psychological factors to which clinicians assessing PFP should show vigilance. They also highlight psychological impairments that might be worthwhile targets in optimising PFP management. PMID- 29794308 TI - Reducing risk of spinal haematoma from spinal and epidural pain procedures. AB - BACKGROUND AND AIMS: Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. METHODS: We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. RESULTS AND RECOMMENDATIONS: Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. CONCLUSIONS: When neuraxial analgesia is considered for a patient on anti-haemostatic medication, with patient-related, or procedure related risk factors, the balance of benefits against risks of bleeding is decisive; when CNB are offered exclusively to patients who will have a reduction of postoperative morbidity and mortality, then a higher risk of bleeding may be accepted. Robust routines should ensure appropriate discontinuation of anti haemostatic drugs and early detection and treatment of SH. IMPLICATIONS: There is an on-going development of drugs for prevention of thromboembolic events following surgery and childbirth. The present practise advisory provides up-to date knowledge and experts' experiences so that patients who will greatly benefit from neuraxial pain procedures and have increased risk of bleeding can safely benefit from these procedures. There are always individual factors for the clinician to evaluate and consider. Increasingly it is necessary for the anaesthesia and analgesia provider to collaborate with specialists in haemostasis. Surgeons and obstetricians must be equally well prepared to collaborate for the best outcome for their patients suffering from acute or chronic pain. Optimal pain management is a prerequisite for enhanced recovery after surgery, but there is a multitude of additional concerns, such as early mobilisation, early oral feeding and ileus prevention that surgeons and anaesthesia providers need to optimise for the best outcome and least risk of complications. PMID- 29794309 TI - The association between back muscle characteristics and pressure pain sensitivity in low back pain patients. AB - BACKGROUND AND AIMS: Some low back pain (LBP) patients recover after every pain episode whereas others develop chronicity. Research indicates that the amount of atrophy and fat infiltration differs between patients with LBP. Also enhanced pain sensitivity is present only in a subgroup of LBP patients. The relationship between pain sensitivity and muscular deformations in LBP, is however unexplored. This study examined the association between pressure pain sensitivity and the structural characteristics of the lumbar muscles in three different groups of non specific LBP patients. METHODS: This cross-sectional study examined the total cross-sectional area (CSA), fat CSA, muscle CSA and muscle fat index (MFI) of the lumbar multifidus (MF) and erector spinae (ES) at level L4 by magnetic resonance imaging in 54 patients with non-specific LBP (23 recurrent LBP, 15 non-continuous chronic LBP and 16 continuous chronic LBP). Pressure pain thresholds were measured at four locations (lower back, neck, hand and leg) by a manual pressure algometer and combined into one "pain sensitivity" variable. As a primary outcome measure, the association between pain sensitivity and muscle structure characteristics was investigated by multiple independent general linear regression models. Secondly, the influence of body mass index (BMI) and age on muscle characteristics was examined. RESULTS: A positive association was found between pain sensitivity and the total CSA of the MF (p=0.006) and ES (p=0.001), and the muscle CSA of the MF (p=0.003) and ES (p=0.001), irrespective of the LBP group. No association was found between pain sensitivity and fat CSA or MFI (p>0.01). Furthermore, a positive association was found between BMI and the fat CSA of the MF (p=0.004) and ES (p=0.006), and the MFI of the MF (p<0.01) and ES (p=0.003). Finally, a positive association was found between age with the fat CSA of the MF (p=0.008) but not with the fat CSA of the ES (p>0.01), nor the MFI of the MF (p>0.01) and ES (p>0.01). CONCLUSIONS: A higher pain sensitivity is associated with a smaller total and muscle CSA in the lumbar MF and ES, and vice versa, but results are independent from the LBP subgroup. On the other hand, the amount of fat infiltration in the lumbar muscles is not associated with pain sensitivity. Instead, a higher BMI is associated with more lumbar fat infiltration. Finally, older patients with LBP are associated with higher fat infiltration in the MF but not in the ES muscle. IMPLICATIONS: These results imply that reconditioning muscular tissues might possibly decrease the pain sensitivity of LBP patients. Vice versa, therapy focusing on enhancement of pain sensitivity might also positively influence the CSA and that way contribute to the recovery of LBP. Furthermore, the amount of lumbar muscle fat seems not susceptible to pain sensitivity or vice versa, but instead a decrease in BMI might decrease the fat infiltration in the lumbar muscles and therefore improve the muscle structure quality in LBP. These hypothesis apply for all non-specific LBP patients, despite the type of LBP. PMID- 29794311 TI - The annual meeting of the Scandinavian Association for the Study of Pain (SASP) 18-20 April 2018. PMID- 29794312 TI - [Results for Treatment of Newly-Diagnosed Glioblastoma Using Carmustine Wafers(Gliadel(r))]. PMID- 29794310 TI - Superior outcomes following cervical fusion vs. multimodal rehabilitation in a subgroup of randomized Whiplash-Associated-Disorders (WAD) patients indicating somatic pain origin-Comparison of outcome assessments made by four examiners from different disciplines. AB - BACKGROUND AND AIMS: Whiplash-Associated Disorders (WAD) are characterized by great variability in long-term symptoms. Patients with central neck and movement induced stabbing pain participated in a randomized study comparing cervical fusion and multimodal rehabilitation. As reported in our previous paper, more patients treated by cervical fusion than by rehabilitation experienced pain relief. Although patient reported outcome measures are a core component of outcome evaluation, independent examiner has been recommended. Because of the heterogeneity of WAD complaints the patients in our study were examined at baseline and follow-up by four experts representing neurology, orthopedics, psychology and physical medicine. The aim was to compare the professional assessments of change both regarding the possible impact of the different examiners' perspectives on individual patient's outcome, and also on the analysis of possible outcome differences between the treatment groups. METHODS: WAD patients with long-term neck pain as the predominant symptom after a traffic accident were eligible. The neck pain origin should be in the midline and perceived as dull and aching, with sudden movement inducing midline stabbing pain. Of the 1,052 patients in contact with our team, 49 were eligible. The overall treatment effect was evaluated on a global outcome transitional scale. The criteria for the scale categories were defined by each expert's professional perspective on change in the whiplash complaints. Statistical methods that take account of the non-metric properties of ordered categorical data were used. Observed inter-expert disagreement was evaluated by the Svensson method that identifies and measures systematic group-related disagreement separately from disagreement caused by individual variation. Possible differences in the distributions of assessments on the expert-specific outcome scales between the treatment groups were analyzed by the Kruskal-Wallis test. RESULTS: The per protocol evaluation showed that a majority of the 18 patients who underwent fusion surgery were assessed as somewhat or much better, ranging from 67% to 78% depending on the expert. Corresponding proportions of improvement in the 17 patients treated by multimodal rehabilitation ranged from 29% to 53%. The statistical analyses confirmed better outcomes in the patients treated by fusion surgery, with p-values ranging from 0.003 to 0.04. The experts' assessments of intra-patient change disagreed more or less for all patients. The analyses of the paired comparisons confirmed that these disagreements could most probably be explained by the different profession-specific operational definitions of the outcome scales rather than by individual variations in data. CONCLUSIONS: The multi-dimensional complexity of WAD-related complaints was comprehensively demonstrated by the inter-disciplinary disagreements in assessing intra-patient outcomes. The superiority of positive treatment effects in patients who underwent cervical fusion compared with multimodal rehabilitation was evident to all experts. IMPLICATIONS: The results strengthen our previous opinion that neck pain in this subgroup of WAD patients has a somatic origin. More than one examiner is recommended for multi-dimensional outcome assessments. PMID- 29794313 TI - [Ultrasound-aided Fixation of a Biodegradable Cranial Fixation System:SonicWeld Rx(r) System in Pediatric Neurosurgery]. AB - PURPOSE: Ultrasound-aided fixation of a biodegradable cranial fixation system called SonicWeld Rx(r), has been widely applied in the fields of craniofacial surgery and plastic surgery. However, there are few reports that denote its use in the field of neurosurgery. This study aimed to evaluate the usefulness of SonicWeld Rx(r) system in pediatric neurosurgery. METHODS: This study included 11 pediatric patients(10 boys, 1 girl), who underwent craniotomy for moyamoya disease, brain tumor, and arachnoid cyst. Their mean age was 6.4 years, ranging from 4 to 10 years. LactoSorb(r) system was applied in 6 patients and SonicWeld Rx(r) system in 5. RESULTS: The time required for screw fixation was significantly shorter in the SonicWeld group(6.5+/-1.4sec)than in the LactoSorb group(13.4+/-2.8sec), with p<0.05. The quality of fixation strength was adequate in both groups. There were no perioperative complications related to the absorbable fixation device. A 3-D skull CT detected no malposition of the bone flap 3 months postoperatively. There were no scalp complications noted for an average of 21 months. CONCLUSION: SonicWeld Rx(r) system can be easy and useful in fixing the bone flap to the cranium in the field of pediatric neurosurgery. PMID- 29794314 TI - [A Case of Ventriculoperitoneal Shunt Dysfunction in an Adult Secondary to Constipation]. AB - INTRODUCTION: Ventriculoperitoneal(VP)shunts function because of the pressure differential between the intracranial space and the peritoneal cavity. Although chronic constipation is often a cause of VP shunt dysfunction in children, it is not well recognized in adults. We present a case of shunt dysfunction that not only resolved after resolution of constipation but also resulted in overdrainage. CASE REPORT: A 28-year-old woman who had a VP shunt placed 11 years prior for hydrocephalus was referred to our department because of an enlarged ventricle diagnosed with computed tomography(CT). She had a previous history of pineal germinoma and a VP shunt was placed to treat the associated hydrocephalus. At presentation, she complained of headache and somnolence. Shunt dysfunction was suspected, but no problem was detected in the shunt system, including pressure settings. As constipation was detected, we treated this condition. Soon after, her symptoms resolved and ventricle size normalized. She was discharged without any deficit, but overdrainage was detected with CT obtained 1 month later. CONCLUSION: Although constipation is not a common cause of shunt dysfunction in adult patients, it is important to consider to avoid unnecessary shunt revision. In the present case, resolution of chronic constipation resulted in resolution of shunt dysfunction. This suggests the importance of resolution of constipation in case of shunt adjustment, even in adult cases. PMID- 29794315 TI - [Postoperative Neurological Deficit due to Transient Hypoperfusion in the Pretreated Contralateral Hemisphere after Bypass Surgery in an Adult Patient with Moyamoya Disease:A Case Report]. AB - Postoperative neurological deficits frequently occur in adult moyamoya disease. In this case report, we describe the time course and disease state of a patient with adult moyamoya disease, who experienced a postoperative neurological deficit due to transient hypoperfusion in the pretreated contralateral hemisphere. A 68 year-old female presented with a sudden onset of left hemianopia due to ischemic moyamoya disease. She had severely low cerebral blood flow(CBF)in the right hemisphere and deterioration of cerebrovascular reactivity in the left hemisphere. First, right combined bypass surgery was performed; subsequently, left combined bypass surgery was performed. Two days after left hemisphere surgery, left hemiparesis gradually appeared. Hypoperfusion of the right hemisphere and hyperperfusion of the left hemisphere were revealed by SPECT and CT perfusion imaging. Blood pressure was controlled to normal levels, and an antiepileptic drug, antiplatelet drug, and edaravone were administered. The patient gradually recovered 2 weeks later, and was able to resume her normal daily life. During the clinical course, laterality of CBF was improved following improvement of clinical symptoms. Abnormal postoperative disproportion of the CBF may occur after revascularization surgery for adult moyamoya disease. Prompt assessment of CBF and proper treatment are needed. PMID- 29794316 TI - [A Case of Cerebellum Abscess due to Fusobacterium nucleatum that Developed Because of Poor Dental Hygiene]. AB - We report a case of cerebellum abscess due to Fusobacterium nucleatum(F. nucleatum) in a 60-year-old man. He was admitted to our hospital complaining of headache and dizziness. On admission, he was lucid with the following vital data:blood pressure, 136/89 mmHg;heart rate, 65 beats/min;body temperature, 37.0C;and oxygen saturation, 100%. He had a moderate headache and could not walk straight. In general, there were no abnormal findings except for his poor dental hygiene. Laboratory findings revealed elevated white blood cell counts(10,900/mm3)and brain MRI revealed a mass shadow that was suspected to be an abscess in the left side of his cerebellum. Elective surgery was scheduled. However, consciousness of disorder was observed on the second hospital day and the size of mass shadow extended;hence, emergent drainage under craniotomy was performed. The diagnosis was cerebellum abscess, and F. nucleatum, which is a normal flora in the oral cavity, was isolated in his cerebellum abscess. After the surgery, his hospital course was positive under the treatment of antibiotics for F. nucleatum. The route of bacterial infection entry was unclear;however, it will be considered that abscesses in the central nervous system occur because of poor dental hygiene. PMID- 29794318 TI - [Dissecting Aneurysm of the Distal Middle Cerebral Artery Formed the Out Pouch during Long-term Follow-up:A Case Report]. AB - A 40-year-old man with a rare case of dissecting aneurysm of the distal middle cerebral artery(MCA, M2 segment)presented with ischemic stroke, manifesting as headache, nausea, and visual disorder. Computed tomography(CT)scan revealed cerebral infarction, and three-dimensional CT angiogram revealed stenotic change at the M2 segment. The patient was conservatively treated and remained neurologically stable. Ten months later, CT scan and magnetic resonance imaging(MRI)revealed outpouching of the M2 segment at the location of the initial stenosis. Angiogram revealed pearl and string sign at the M2 segment of the inferior trunk. The preoperative diagnosis was spontaneous dissecting aneurysm of the right distal MCA. The patient was treated with direct surgery for aneurysm resection and revascularization using the superficial temporal artery. The brain surface in contact with the dissecting aneurysm was colored xanthochromic, so minor bleeding from the dissecting aneurysm was highly suspected. Previously, 19 cases of dissecting aneurysm of the distal MCA have been reported. Distal dissecting aneurysms seem to rupture more frequently in the MCA than in the proximal segment. Long-term follow-up MRI and angiogram might be important, not only in the acute stage in patients with atypical caliber changes in the distal MCA. Immediate direct surgery is indicated to avoid hemorrhagic stroke if dilatation of the major trunk at the dissection is suspected. PMID- 29794317 TI - [An Unusual Case of Acute Epidural Hematoma Showing Rapid Spontaneous Resolution with Delayed Recurrence]. AB - A 16-year-old boy collided with a passenger car while riding a motorcycle. He was thrown to a distance and experienced a head injury on impact. When brought to our medical facility, he was alert, had no neurological abnormalities, and did not complain of headache. A head computed tomography(CT)scan indicated a left cranial fracture and an acute epidural hematoma(15mm thick)directly under the fracture. Follow-up head CT performed 3 hours after the injury indicated no change in the size of the hematoma. The head CT performed on the following day indicated that most of the hematoma had disappeared. As the patient had neither headache nor neurological symptoms, he was placed under observation. However, a head CT performed 7 days after the injury indicated the formation of an epidural hematoma approximately the same size as the initial hematoma and located at the same site. We performed craniotomy to evacuate the hematoma, identify the source of the bleeding, and restore hemostasis. Although cases in which an acute epidural hematoma rapidly and spontaneously resolves have been reported, these are extremely rare. Recurrence of an epidural hematoma despite normal blood coagulation function after its initial rapid resolution has not been reported yet. We report on this rare case of acute epidural hematoma with reference to relevant literatures. PMID- 29794319 TI - [Multiple Spinal Intradural and Extradural Syphilis Granuloma Mimicking Lumbar Dumbbell Type Neurinoma:A Case Report]. AB - Spinal intradural and extradural syphilis granuloma is extremely rare. Here, we report a patient with multiple spinal intradural and extradural syphilis granuloma mimicking dumbbell type neurinoma. The patient was a 68-year-old man, who presented with left femoral pain for a month. Magnetic resonance imaging(MRI)revealed a homogeneous enhanced dumbbell-shaped lesion occupying the spinal canal at the level of lumbar 3/4 and developing through the intervertebral foramen. Although initial blood tests revealed that he contracted with the syphilis, we diagnosed dumbbell type neurinoma preoperatively. He underwent partial tumor removal. The tumor adhered tightly to the cauda equina in intraoperative finding. Histopathological diagnosis of the lesion was granulomatous inflammation with the lymphocytic infiltration. Postoperatively, results of the Treponema pallidum hemagglutination(TPHA)test and the rapid plasma regain(RPR)test of cerebrospinal fluid were reactive, so we confirmed syphilis granuloma. He was treated with penicillin G for two weeks from 25 days after surgery. A follow-up MRI of the lumbar spine 51 days after surgery showed a reduction in size of the lumbar spinal tumor compared to the initial findings. Thus, syphilis granuloma should be considered in differential diagnosis of a spinal dumbbell shaped lesion. Penicillin G may be effective for the treatment of syphilis granuloma. PMID- 29794320 TI - [Clot Retrieval Treatment for Infectious Embolus due to Infective Endocarditis:A Case Report]. PMID- 29794322 TI - [Preoperative Diffusion MR Images may be Necessary for Patients with Chronic Subdural Hematoma]. PMID- 29794321 TI - [(5)Advance in Latest Devices and Systems of Deep Brain Stimulation]. PMID- 29794325 TI - Magnetic field induced metal-insulator transition in single nodal ring topological semimetals. AB - Our theoretical investigation indicates that an applied magnetic field can open a gap between the conduction and valence bands of a nodal line semimetal (NLSM), though it is a kind of gapless material in the absence of a magnetic field. The emerging bandgap depends sensitively on the strength and orientation of the magnetic field which implies a tunable and large anisotropy of magnetoresistance in such kinds of topological materials. Following such a theoretical finding, we predict that in some candidates of NSLMs with a single nodal ring, such as the materials of CaP3 family, a transition between metallic and insulating states driven by a magnetic field is possibly observed experimentally. Consequently, a magnetic field can be viewed as a novel mechanism for metal-insulator transition of solid materials, in additional to the well-known conventional ones such as the Anderson and Mott transitions. PMID- 29794324 TI - Magnetic responsive cell-based strategies for diagnostics and therapeutics. AB - The potential of magnetically assisted strategies within the remit of cell-based therapies is increasing, creating new opportunities for biomedical platforms and in the field of tissue engineering and regenerative medicine. Among the magnetic elements approached for building magnetically responsive strategies, superparamagnetic iron oxide nanoparticles (SPIONs) represent tunable and precise tools whose properties can be modelled for detection, diagnosis, targeting and therapy purposes. The most investigated clinical role of SPIONs is as contrast imaging agents for tracking and monitoring cells and tissues. Nevertheless, magnetic detection also includes biomarker mapping, cell labelling and cell/drug targeting to monitor cell events and anticipate the disruption of homeostatic conditions and the progression of disease. Additionally, the isolation and screening techniques of cell subsets in heterogeneous populations or of proteins of interest have been explored in a magnetic sorting context. More recently, SPION-based technologies have been applied to stimulate cell differentiation and mechanotransduction processes and to transport genetic or drug cargo to study biological mechanisms and contribute to improved therapies. Magnetically based strategies significantly contribute to magnetic tissue engineering (magTE), in which magnetically responsive actuators built from magnetic labelled cells or magnetic functionalized systems can be remotely controlled and spatially manipulated upon the actuation of an external magnetic field for the delivery or target of TE solutions. SPION functionalities combined with magnetic responsiveness in multifactorial magnetically assisted platforms can revolutionize diagnosis and therapeutics, providing new diagnosis and theranostic tools, encouraging regenerative medicine approaches and having potential for more effective therapies. This review will address the contribution of SPION-based technologies as multifunctional tools in boosting magnetically assisted cell based strategies to explore diagnostics and tracking solutions for the detection and analysis of pathologies, and to generate improved treatments and therapies, envisioning precise and customized answers for the management of numerous diseases. PMID- 29794323 TI - Aligned fibrous PVDF-TrFE scaffolds with Schwann cells support neurite extension and myelination in vitro. AB - OBJECTIVE: Polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE), which is a piezoelectric, biocompatible polymer, holds promise as a scaffold in combination with Schwann cells (SCs) for spinal cord repair. Piezoelectric materials can generate electrical activity in response to mechanical deformation, which could potentially stimulate spinal cord axon regeneration. Our goal in this study was to investigate PVDF-TrFE scaffolds consisting of aligned fibers in supporting SC growth and SC-supported neurite extension and myelination in vitro. APPROACH: Aligned fibers of PVDF-TrFE were fabricated using the electrospinning technique. SCs and dorsal root ganglion (DRG) explants were co-cultured to evaluate SC supported neurite extension and myelination on PVDF-TrFE scaffolds. MAIN RESULTS: PVDF-TrFE scaffolds supported SC growth and neurite extension, which was further enhanced by coating the scaffolds with Matrigel. SCs were oriented and neurites extended along the length of the aligned fibers. SCs in co-culture with DRGs on PVDF-TrFE scaffolds promoted longer neurite extension as compared to scaffolds without SCs. In addition to promoting neurite extension, SCs also formed myelin around DRG neurites on PVDF-TrFE scaffolds. SIGNIFICANCE: This study demonstrated PVDF-TrFE scaffolds containing aligned fibers supported SC-neurite extension and myelination. The combination of SCs and PVDF-TrFE scaffolds may be a promising tissue engineering strategy for spinal cord repair. PMID- 29794326 TI - Concurrent segregation and erosion effects in medium-energy iron beam patterning of silicon surfaces. AB - We have bombarded crystalline silicon targets with a 40 keV Fe+ ion beam at different incidence angles. The resulting surfaces have been characterized by atomic force, current-sensing and magnetic force microscopies, scanning electron microscopy, and x-ray photoelectron spectroscopy. We have found that there is a threshold angle smaller than 40 degrees for the formation of ripple patterns, which is definitely lower than those frequently reported for noble gas ion beams. We compare our observations with estimates of the value of the critical angle and of additional basic properties of the patterning process, which are based on a continuum model whose parameters are obtained from binary collision simulations. We have further studied experimentally the ripple structures and measured how the surface slopes change with the ion incidence angle. We explore in particular detail the fluence dependence of the pattern for an incidence angle value (40 degrees ) close to the threshold. Initially, rimmed holes appear randomly scattered on the surface, which evolve into large, bug-like structures. Further increasing the ion fluence induces a smooth, rippled background morphology. By means of microscopy techniques, a correlation between the morphology of these structures and their metal content can be unambiguously established. PMID- 29794327 TI - Corrigendum: Rapid freezing of water under dynamic compression (2018 J. Phys.: Condens. Matter 30 233002). AB - Corrigendum. PMID- 29794328 TI - The influence of the entry region on the instability of a coflowing injector device. AB - The occurrence of dripping and jetting regimes in a microfluidic coflowing injector device has been related recently to the spatio-temporal stability properties of the developed velocity profile. Dripping corresponds to an absolutely unstable flow while jetting is observed when the Rayleigh-Plateau instability of the core-annular jet is convective. In this work we take into account the effect of the entry region on the dripping to jetting transition by carrying out a global stability analysis of the steady two-phase base flow. We show that, depending on the flow parameters, the entry region can affect significantly the transition between the two regimes. PMID- 29794329 TI - In vivo ultrasound imaging of the bone cortex. AB - Current clinical ultrasound scanners cannot be used to image the interior morphology of bones because these scanners fail to address the complicated physics involved for exact image reconstruction. Here, we show that if the physics is properly addressed, bone cortex can be imaged using a conventional transducer array and a programmable ultrasound scanner. We provide in vivo proof for this technique by scanning the radius and tibia of two healthy volunteers and comparing the thickness of the radius bone with high-resolution peripheral x-ray computed tomography. Our method assumes a medium that is composed of different homogeneous layers with unique elastic anisotropy and ultrasonic wave-speed values. The applicable values of these layers are found by optimizing image sharpness and intensity over a range of relevant values. In the algorithm of image reconstruction we take wave refraction between the layers into account using a ray-tracing technique. The estimated values of the ultrasonic wave-speed and anisotropy in cortical bone are in agreement with ex vivo studies reported in the literature. These parameters are of interest since they were proposed as biomarkers for cortical bone quality. In this paper we discuss the physics involved with ultrasound imaging of bone and provide an algorithm to successfully image the first segment of cortical bone. PMID- 29794330 TI - A design for a dynamic biomimetic sonarhead inspired by horseshoe bats. AB - The noseleaf and pinnae of horseshoe bats (Rhinolophus ferrumequinum) have both been shown to actively deform during biosonar operation. Since these baffle structures directly affect the properties of the animals biosonar system, this work mimics horseshoe bat sonar system with the goal of developing a platform to study the dynamic sensing principles horseshoe bats employ. Consequently, two robotic devices were developed to mimic the dynamic emission and reception characteristics of horseshoe bats. The noseleaf and pinnae shapes were modeled as smooth blanks matched to digital representations of a horseshoe bat specimens noseleaf and pinnae. Local shape features mimicking structures on the pinnae and noseleaf were added digitally. Flexible baffles with local shape feature combinations were manufactured and paired with actuation mechanisms to mimic pinnae and noseleaf deformations in vivo. Two noseleaves with and without local shape features were considered. Each noseleaf baffle was mounted to a platform called the dynamic emission head to actuate three surface elements of the baffle. Similarly, 12 pinna realizations composed of combinations of three local shape features were mounted to a platform called the dynamic reception head to deform the left and right pinnae independently. Motion of the noseleaf and pinnae were synchronized to the incoming and outgoing sonar waveform, and the joint time frequency properties of the noseleaf and pinnae local feature combinations and pairs of pinnae and noseleaf thereof were characterized across spatial direction. Amplitude modulations to the outgoing and incoming sonar pulse information across spatial direction were observed for all pinnae and noseleaf local shape feature combinations. Peak modulation variance generated by motion of the pinnae and combinations of the noseleaf and pinnae approached a white Gaussian noise variance bound. It was found the dynamic emitter generated less modulation than either the combined or reception scenarios. PMID- 29794331 TI - Laser-etch patterning of metal oxide coated carbon nanotube 3D architectures. AB - This paper describes a way to fabricate novel hybrid low density nanostructures containing both carbon nanotubes (CNTs) and ceramic nanotubes. Using atomic layer deposition, a thin film of aluminum oxide was conformally deposited on aligned multiwall CNT foams in which the CNTs make porous, three-dimensional interconnected networks. A CO2 laser was used to etch pure alumina nanotube structures by burning out the underlying CNT substrate in discrete locations via the printed laser pattern. Structural and morphological transitions during the calcination process of aluminum oxide coated CNTs were investigated through in situ transmission electron microscopy and high-resolution scanning electron microscopy. Laser parameters were optimized to etch the CNT away (i.e. etching speed, power and focal length) while minimizing damage to the alumina nanotubes due to overheating. This study opens a new route for fabricating very low density three dimensionally patterned materials with areas of dissimilar materials and properties. To demonstrate the attributes of these structures, the etched areas were used toward anisotropic microfluidic liquid flow. The demonstration used the full thickness of the material to make complex pathways for the liquid flow in the structure. Through tuning of processing conditions, the alumina nanotube (etched) regions became hydrophilic while the bulk material remained hydrophobic and electrically conductive. PMID- 29794332 TI - Theory of pore-driven and end-pulled polymer translocation dynamics through a nanopore: an overview. AB - We review recent progress on the theory of dynamics of polymer translocation through a nanopore based on the iso-flux tension propagation (IFTP) theory. We investigate both pore-driven translocation of flexible and a semi-flexible polymers, and the end-pulled case of flexible chains by means of the IFTP theory and extensive molecular dynamics (MD) simulations. The validity of the IFTP theory can be quantified by the waiting time distributions of the monomers which reveal the details of the dynamics of the translocation process. The IFTP theory allows a parameter-free description of the translocation process and can be used to derive exact analytic scaling forms in the appropriate limits, including the influence due to the pore friction that appears as a finite-size correction to asymptotic scaling. We show that in the case of pore-driven semi-flexible and end pulled polymer chains the IFTP theory must be augmented with an explicit trans side friction term for a quantitative description of the translocation process. PMID- 29794333 TI - Facile synthesis of AuPd nanoparticles anchored on TiO2 nanosheets for efficient dehydrogenation of formic acid. AB - Safe and efficient hydrogen storage is one of the key technologies for the widespread utilization of hydrogen energy. Formic acid (FA) is regarded as a safe and convenient chemical hydrogen storage material. However, the lack of highly efficient heterogeneous catalysts hinders its practical application. Herein, we presented a facile wet-impregnated deposition method to synthesize ultrafine AuPd alloy nanoparticles anchored on TiO2 nanosheets (AuPd/TiO2 nanosheets) which were used as high efficient catalysts for the dehydrogenation of FA. TiO2 nanosheets were calcined at different temperatures to modify the catalytic activity of catalyst. AuPd/TiO2 nanosheets-400 exhibits the superior activity for catalyzing the FA to release 96% of overall hydrogen content with an initial turnover frequency value of 592 mol H2 mol-1 metal h-1 at 25 degrees C and low activation energy of 11.8 kJ mol-1. Detailed characterizations show that the superior catalytic performance can be ascribed to the alloy structure of AuPd centers, the phase and crystallinity of TiO2 nanosheets, and the strong electron transfer interaction between AuPd nanoparticles and TiO2 nanosheets substrate. PMID- 29794334 TI - Comparative study of DFT+U functionals for non-collinear magnetism. AB - We performed comparative analysis for DFT+U functionals to better understand their applicability to non-collinear magnetism. Taking LiNiPO4 and Sr2IrO4 as examples, we investigated the results out of two formalisms based on charge-only density and spin density functional plus U calculations. Our results show that the ground state spin order in terms of tilting angle is strongly dependent on Hund J. In particular, the opposite behavior of canting angles as a function of J is found for LiNiPO4. The dependence on the other physical parameters such as Hubbard U and Slater parameterization [Formula: see text] is investigated. We also discuss the formal aspects of these functional dependences as well as parameter dependences. The current study provides useful information and important intuition for the first-principles calculation of non-collinear magnetic materials. PMID- 29794335 TI - Suppression of ferromagnetic order by Ag-doping: a neutron scattering investigation on Ce2(Pd1-x Ag x )2In (x = 0.20, 0.50). AB - The ground state magnetic behaviour of Ce2(Pd0.8Ag0.2)2In and Ce2(Pd0.5Ag0.5)2In, found in the ferromagnetic branch of Ce2Pd2In, has been investigated by neutron powder diffraction at low temperature. Ce2(Pd0.8Ag0.2)2In is characterized by a ferromagnetic structure with the Ce moments aligned along the c-axis and values of 0.96(2) u B. The compound retains the P4/mbm throughout the magnetic transition, although the magnetic ordering is accompanied by a significant decrease of the lattice strain along [0 0 l], suggesting a magnetostructural contribution. The magnetic behaviour of Ce2(Pd0.5Ag0.5)2In is very different; this compound exhibits an extremely reduced magnetic scattering contribution in the diffraction pattern, that can be ascribed to a different kind of ferromagnetic ordering, with extremely reduced magnetic moments (~0.1 u B) aligned along [0 l 0]. These results point to a competition between different types of magnetic correlations induced by Ag-substitution, giving rise to a magnetically frustrated scenario in Ce2(Pd0.5Ag0.5)2In. PMID- 29794336 TI - Regional lung ventilation and perfusion by electrical impedance tomography compared to single-photon emission computed tomography. AB - OBJECTIVE: Electrical impedance tomography (EIT) is a noninvasive imaging modality that allows real-time monitoring of regional lung ventilation ([Formula: see text]) in intensive care patients at bedside. However, for improved guidance of ventilation therapy it would be beneficial to obtain regional ventilation-to perfusion ratio ([Formula: see text]) by EIT. APPROACH: In order to further explore the feasibility, we first evaluate a model-based approach, based on semi negative matrix factorization and a gamma-variate model, to extract regional lung perfusion ([Formula: see text]) from EIT measurements. Subsequently, a combined validation of both [Formula: see text] and [Formula: see text] measured by EIT against single-photon emission computed tomography (SPECT) is performed on data acquired as part of a porcine animal trial. Four pigs were ventilated at two different levels of positive end-expiratory pressure (PEEP 0 and 15 cm H2O, respectively) in randomized order. Repeated injections of an EIT contrast agent (NaCl 10%) and simultaneous SPECT measurements of [Formula: see text] (81mKr gas) and [Formula: see text] (99mTc-labeled albumin) were performed. MAIN RESULTS: Both [Formula: see text] and [Formula: see text] from EIT and SPECT were compared by correlation analysis. Very strong (r 2 = 0.94 to 0.95) correlations were found for [Formula: see text] and [Formula: see text] in the dorsal-ventral direction at both PEEP levels. Moderate (r 2 = 0.36 to 0.46) and moderate to strong (r 2 = 0.61 to 0.82) correlations resulted for [Formula: see text] and [Formula: see text] in the right-left direction, respectively. SIGNIFICANCE: The results of combined validation indicate that monitoring of [Formula: see text] and [Formula: see text] by EIT is possible. However, care should be taken when trying to quantify [Formula: see text] by EIT, as imaging artefacts and model bias may void necessary spatial matching. PMID- 29794337 TI - Engineering approaches of smart, bio-inspired vesicles for biomedical applications. AB - Advances in materials engineering have allowed for the development of sophisticated and controlled drug delivery through vesicles. Smart vesicles, capable of sensing single stimulus or multiple stimuli, can be engineered to process specific environmental signals to produce a tailored response. Exhibiting multifunctionality and theranostic abilities, they are a promising platform for new therapeutic methods. Here, we discuss smartness in the context of biosensing vesicles, followed by the various components required to develop a smart vesicle and the design considerations regarding engineering approaches of each. We then focus on biomedical applications of the vesicles in disease treatment and biosensing. PMID- 29794338 TI - Tumor-on-a-chip platforms for assessing nanoparticle-based cancer therapy. AB - Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP based cancer therapy techniques, and then present the latest advances in 'tumor on-a-chip' platforms that can potentially facilitate clinical translation of NP based cancer therapies. PMID- 29794339 TI - Comparison of photoplethysmogram measured from wrist and finger and the effect of measurement location on pulse arrival time. AB - OBJECTIVE: The aim of this paper was to compare photoplethysmogram (PPG) signals measured from the wrist and finger and to evaluate if wrist PPG signal could be used to calculate pulse arrival time (PAT), the time delay between electrocardiogram (ECG) R peak and a feature (e.g. peak, foot, first derivative peak) in the PPG signal. Further, the correlation between pulse wave velocity (rePWV, defined as PWV from ECG R peak to extremity) and systolic blood pressure was studied. APPROACH: Thirty subjects were measured at rest by a trained research nurse. For reference measurement, chest ECG and finger PPG were measured using commercial sensors. Wrist PPG and arm ECG were measured with a custom-made setup, where the PPG sensor was located at the back surface of the forearm. MAIN RESULTS: Reference finger and wrist PPG signals were found to differ in shape and also in amplitude. The PPG foot or first derivative peak detection methods seemed to be the most suitable methods for wrist PAT calculation. The Pearson correlation coefficient between blood pressure and rePWV was found to be 0.44 for the reference finger measurement and 0.37 for the wrist measurement. SIGNIFICANCE: Wrist PPG signal is widely used in optical heart rate monitors. Based on the results obtained in this study, wrist PPG signal may be used also for PAT calculation. The use of PAT for blood pressure estimation still has challenges, but PAT as such could be used as an interesting indicator of vascular health. PMID- 29794340 TI - A support vector machine approach for AF classification from a short single-lead ECG recording. AB - OBJECTIVE: In this paper, a support vector machine (SVM) approach using statistical features, P wave absence, spectrum features, and length-adaptive entropy are presented to classify ECG rhythms as four types: normal rhythm, atrial fibrillation (AF), other rhythm, and too noisy to classify. APPROACH: The proposed algorithm consisted of three steps: (1) signal pre-processing based on the wavelet method; (2) feature extraction, the extracted features including one power feature, two spectrum features, two entropy features, 17 RR interval related features, and 11 P wave features; and (3) classification using the SVM classifier. MAIN RESULTS: The algorithm was trained by 8528 single-lead ECG recordings lasting from 9 s to just over 60 s and then tested on a hidden test set consisting of 3658 recordings of similar lengths, which were all provided by the PhysioNet/Computing in Cardiology Challenge 2017. The scoring for this challenge used an F 1 measure, and the final F 1 score was defined as the average of F 1n (the F 1 score of normal rhythm), F 1a (the F 1 score of AF rhythm), and F 1o (the F 1 score of other rhythm). The results confirmed the high accuracy of our proposed method, which obtained 90.27%, 86.37%, and 75.08% for F 1n , F 1a , and F 1n and the final F 1 score of 84% on the training set. In the final test to assess the performance of all of the hidden data, the obtained F 1n , F 1a , F 1o and the average F 1 were 90.82%, 78.56%, 71.77% and 80%, respectively. SIGNIFICANCE: The proposed algorithm targets a large number of raw, short single ECG data rather than a small number of carefully selected, often clean ECG records, which have been studied in most of the previous literature. It breaks through the limitation in applicability and provides reliable AF detection from a short single-lead ECG. PMID- 29794341 TI - Calcium and phosphate ions as simple signaling molecules with versatile osteoinductivity. AB - Due to the continually increasing clinical need to heal large bone defects, synthetic bone graft substitutes have become ever more necessary with calcium phosphates (CaP) widely used due to their similarity to the mineral component of bone. In this research, different concentrations of calcium ions (Ca2+), phosphate ions (Pi), or their combination were provided to mesenchymal stem cells (MSCs) to evaluate their influence on proliferation and differentiation. The results suggest that 1-16 mM Ca2+ and 1-8 mM Pi is osteoinductive, but not cytotoxic. Furthermore, three distinct calcium phosphates (i.e. monobasic, dibasic, and hydroxyapatite) with different dissolution rates were investigated for their Ca2+ and Pi release. These biomaterials were then adjusted to release ion concentrations within the established therapeutics window for which MSC bioactivity was assessed. These findings suggest that CaP-based biomaterials can be leveraged to achieve Ca2+ and Pi dose-dependent osteoinduction for bone regenerative engineering applications. PMID- 29794342 TI - Multiclass classification of obstructive sleep apnea/hypopnea based on a convolutional neural network from a single-lead electrocardiogram. AB - OBJECTIVE: In this paper, we propose a convolutional neural network (CNN)-based deep learning architecture for multiclass classification of obstructive sleep apnea and hypopnea (OSAH) using single-lead electrocardiogram (ECG) recordings. OSAH is the most common sleep-related breathing disorder. Many subjects who suffer from OSAH remain undiagnosed; thus, early detection of OSAH is important. APPROACH: In this study, automatic classification of three classes-normal, hypopnea, and apnea-based on a CNN is performed. An optimal six-layer CNN model is trained on a training dataset (45 096 events) and evaluated on a test dataset (11 274 events). The training set (69 subjects) and test set (17 subjects) were collected from 86 subjects with length of approximately 6 h and segmented into 10 s durations. MAIN RESULTS: The proposed CNN model reaches a mean [Formula: see text]-score of 93.0 for the training dataset and 87.0 for the test dataset. SIGNIFICANCE: Thus, proposed deep learning architecture achieved a high performance for multiclass classification of OSAH using single-lead ECG recordings. The proposed method can be employed in screening of patients suspected of having OSAH. PMID- 29794343 TI - High-speed large area atomic force microscopy using a quartz resonator. AB - A high-speed atomic force microscope for scanning large areas, utilizing a quartz bar driven close to resonance to provide the motion in the fast scan axis is presented. Images up to 170 * 170 MUm2 have been obtained on a polydimethylsiloxane (PDMS) grating in 1 s. This is provided through an average tip-sample velocity of 28 cm s-1 at a line rate of 830 Hz. Scan areas up to 80 * 80 MUm2 have been obtained in 0.42 s with a line rate of 1410 Hz. To demonstrate the capability of the scanner the spherulitic crystallization of a semicrystalline polymer was imaged in situ at high speed. PMID- 29794345 TI - Bubble growth in cylindrically-shaped optical absorbers during photo-mediated ultrasound therapy. AB - Photo-mediated ultrasound therapy (PUT) is a non-invasive, agent-free technique to shut down microvessels with high precision by promoting cavitation activity precisely in the targeted microvessels. PUT is based on the photoacoustic (PA) cavitation generated through concurrently applied nanosecond laser pulses and ultrasound bursts. In this study, a PA cavitation model is employed to understand the enhanced cavitation activity during PUT, with full consideration of the optical absorption of blood vessels. Bubble size evolution in cylindrically shaped optical absorbers (vessels) due to rectified diffusion is simulated. Results show that the ultrasound pressure required for bubble growth decreases dramatically with the increased laser fluence. At a relatively low ultrasound driving pressure, bubble equilibrium radius increases rapidly due to concurrently applied nanosecond laser pulses and ultrasound bursts, resulting in a transition from inertial cavitation to stable cavitation. This inertial to stable transition is verified by the experimentally measured results on 0.76 mm silicone tubes filled with human whole blood with 0.5 MHz ultrasound at 0.243 MPa. This study demonstrated the potential to induce stable bubbles in blood vessels by PUT non invasively. PMID- 29794344 TI - Performance of marrow stromal cell-seeded small-caliber multilayered vascular graft in a senescent sheep model. AB - Failure of small-caliber grafts, used as bypass or reconstructive grafts in cardiovascular treatments, is often caused by thrombosis and stenosis. We have developed a multilayered, compliant graft with an electrospun heparin encapsulated core and collagen-chitosan shell. Herein, the performances of acellular and cell-seeded grafts were evaluated in adult sheep for preclinical assessment. Allogeneic ovine marrow stroma cells (MSCs) were uniformly attached to the lumen of cell-seeded grafts. Interposition grafts were used for carotid arteries. Four grafts were tested for each type. Upon implantation, all grafts successfully restored perfusion and rhythmically deformed under pulsatile arterial flow. Weekly ultrasonography and Doppler revealed that all grafts remained patent for perfusion during the course of one-month study. No formation of blood clots or other complications were found. The diameter of graft lumen did not vary significantly over the time or with the graft type, while narrowing at anastomosis and significant thickening of graft wall were found in both types of grafts. More significant neotissue formation was found at anastomotic sections of acellular controls compared to cell-seeded grafts. Results from histological and immunofluorescent analyses revealed moderate intimal hyperplasia (IH) at anastomosis. When compared to cell-seeded grafts, acellular controls presented thicker IH composed of alpha-smooth muscle actin positive cells and ground substances, which correlated with reduced and more disturbing flow. IH was thickest at anastomosis and tapered off to a minimum in the mid-section. Few PECAM-positive cells appeared on cell-seeded grafts but not acellular controls. Additionally, lesser graft thickening was found in cell-seed grafts, which might be associated with the function of stromal cells in altering the fibrotic process during tissue repair. Results suggest that MSCs held the potential to reduce hyperplasia and improve healing in an aged, large animal model for vascular grafting. PMID- 29794346 TI - Promote quantitative ischemia imaging via myocardial perfusion CT iterative reconstruction with tensor total generalized variation regularization. AB - Myocardial perfusion computed tomography (MPCT) imaging is commonly used to detect myocardial ischemia quantitatively. A limitation in MPCT is that an additional radiation dose is required compared to unenhanced CT due to its repeated dynamic data acquisition. Meanwhile, noise and streak artifacts in low dose cases are the main factors that degrade the accuracy of quantifying myocardial ischemia and hamper the diagnostic utility of the filtered backprojection reconstructed MPCT images. Moreover, it is noted that the MPCT images are composed of a series of 2/3D images, which can be naturally regarded as a 3/4-order tensor, and the MPCT images are globally correlated along time and are sparse across space. To obtain higher fidelity ischemia from low-dose MPCT acquisitions quantitatively, we propose a robust statistical iterative MPCT image reconstruction algorithm by incorporating tensor total generalized variation (TTGV) regularization into a penalized weighted least-squares framework. Specifically, the TTGV regularization fuses the spatial correlation of the myocardial structure and the temporal continuation of the contrast agent intake during the perfusion. Then, an efficient iterative strategy is developed for the objective function optimization. Comprehensive evaluations have been conducted on a digital XCAT phantom and a preclinical porcine dataset regarding the accuracy of the reconstructed MPCT images, the quantitative differentiation of ischemia and the algorithm's robustness and efficiency. PMID- 29794347 TI - Assessment of sequence dependent geometric distortion in contrast-enhanced MR images employed in stereotactic radiosurgery treatment planning. AB - This work focuses on MR-related sequence dependent geometric distortions, which are associated with B 0 inhomogeneity and patient-induced distortion (susceptibility differences and chemical shift effects), in MR images used in stereotactic radiosurgery (SRS) applications. Emphasis is put on characterizing distortion at target brain areas identified by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) paramagnetic contrast agent uptake. A custom-made phantom for distortion detection was modified to accommodate two small cylindrical inserts, simulating small brain targets. The inserts were filled with Gd-DTPA solutions of various concentrations (0-20 mM). The phantom was scanned at 1.5 T unit using both the reversed read gradient polarity (to determine the overall distortion as reflected by the inserts centroid offset) and the field mapping (to determine B 0 inhomogeneity related distortion in the vicinity of the inserts) techniques. Post-Gd patient images involving a total of 10 brain metastases/targets were also studied using a similar methodology. For the specific imaging conditions, contrast agent presence was found to evidently affect phantom insert position, with centroid offset extending up to 0.068 mm mM 1 (0.208 ppm mM-1). The Gd-DTPA induced distortion in patient images was of the order of 0.5 mm for the MRI protocol used, in agreement with the phantom results. Total localization uncertainty of metastases-targets in patient images ranged from 0.35 mm to 0.87 mm, depending on target location, with an average value of 0.54 mm (2.24 ppm). This relative wide range of target localization uncertainty results from the fact that the B 0 inhomogeneity distortion vector in a specific location may add to or partly counterbalance Gd-DTPA induced distortion, thus increasing or decreasing, respectively, the total sequence dependent distortion. Although relatively small, the sequence dependent distortion in Gd-DTPA enhanced brain images can be easily taken into account for SRS treatment planning and target definition purposes by carefully inspecting both the forward and reversed polarity series. PMID- 29794348 TI - New possibilities for aligners. PMID- 29794349 TI - The Horseshoe Jet for miniscrew-supported molar distalization. PMID- 29794350 TI - Space management with Invisalign for interdisciplinary orthodontic treatment. PMID- 29794351 TI - Combining skeletal anchorage and intermaxillary elastics in Class II treatment. PMID- 29794352 TI - Intrusion of a supraerupted maxillary second molar using a modified cantilever appliance. PMID- 29794353 TI - Ransomware: Is your practice protected? PMID- 29794354 TI - 2018 Eugene L. Gottlieb JCO Student of the Year: Dr. Samaneh Mojarrad. PMID- 29794355 TI - Updates on the use of vaccines in dermatological conditions. AB - Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper. PMID- 29794356 TI - Bloom syndrome sans characteristic facial features in a Mestizo patient- a diagnostic challenge. PMID- 29794357 TI - Laparoscopic parastomal hernia repair: A modified technique of mesh placement in Sugarbaker procedure. AB - Introduction: Conventional surgery for parastomal hernia entails primary suture repair or stoma relocation. Laparoscopic surgery has advantages of less pain, faster post-operative recovery and better cosmesis. While the Sugarbaker technique has been valued for least recurrences, however, it exposes the stomal loop to the parietal surface of the mesh exposing it to complications. We report a modification of mesh placement after primary defect repair to improvise the safety of meshplasty and to minimise mesh erosions into the stomal loop of bowel. Patients and Methods: Patients with permanent stoma presenting with a parastomal bulge leading to difficulty with stoma care or abdominal distention or pain were included in the study. A pre-operative computed tomography scan was performed in all patients to rule out any recurrence of primary pathology for which stoma was created and to study the abdominal musculature and defects. Results: Of 14 patients, 12 patients had end-sigmoid stoma, one had end ileostomy following surgery for ulcerative colitis and one had urinary conduit. The size of the defect varied from 4.5 cm to 6 cm in diameter, and the average duration of surgery was 125 min. Pain assessed on VAS score was higher in the first 12 h, and all were started on orals on the next day, and average hospital stay was 4.2 days. The longest follow-up of 7 years and shortest of 15 months did not reveal any complications as recurrence, seroma, mesh infections or erosions into the stoma. Conclusion: Modified placement of composite mesh is safe and helps in minimising mesh-related complications of the Sugarbaker technique for parastomal hernias. PMID- 29794358 TI - 'Little old lady's hernia' (obturator hernia): A deceptive encounter. AB - Obturator hernia (OH) is rare which not only carries high mortality amongst all abdominal hernia, but also known for the difficulty in diagnosing it. Howship Romberg sign is a clinical sign to diagnose OH, but due to the lower-limb muscle contractures, it was not possible in our case. Computed tomography scan becomes the investigation of choice in this situation. A laparoscopic approach can be used safely. PMID- 29794359 TI - Surgery strategy of 13 cases to control bleeding from the liver on laparoscopic repeat liver resection for recurrent hepatocellular carcinoma. AB - Introduction: Laparoscopic repeat liver resection (LRLR) is a safe and effective treatment in recurrent hepatocellular carcinoma (rHCC) in particular patients. However, there are less reports about surgery strategy of LRLR for rHCC. The aim of this study was to perform a systematic strategy for bleeding of liver to increase the safety and feasibility of LRLR for rHCC. Methods: In this study, a total of 13 cases of LRLR for rHCC, including 8 males and 5 females; aged 28-72 years, mean age 54 years, who were received at least one laparotomy due to HCC. We employ to block the local blood flow, ligation of the left or right hepatic artery and/or approach of Pringle according to the assessment of the degree of adhesions in the abdominal and the first hepatic portal, the location of the tumour (edge/central). Results: Three cases were less adhesions, nine cases were dense adhesions but 1 case was serious adhesions. Two cases were employed to block the local blood flow, 3 cases were employed to ligation of the left or right hepatic artery and 7 cases were employed to approach of Pringle. Twelve cases were successfully completed by LRLR whereas 1 case was completed by transfer to the open resection, including massive resection in 3 cases (the diameter of resection >=3 cm), small hepatectomy in 10 cases (the diameter of resection < 3 cm), no severe perioperative complication. The average operative time was (142 +/- 34) min, the average intraoperative blood loss was (251 +/- 92) ml and the average post-operative hospital time was (9 +/- 3) d. The mean follow up time was 25 months. Until the last follow-up, 11 cases survived while 2 cases died because of tumour recurrence. Conclusions: It can improve the safety and feasibility of LRLR for rHCC, according to the degree of adhesion of the peritoneal adhesions and the first hepatic portal, then selecting the appropriate technique to control the bleeding of the hepatectomy. PMID- 29794360 TI - Easy and effective way to evaluate the urological complication during laparoscopic gynaecologic surgery. PMID- 29794361 TI - Extended totally extraperitoneal repair (eTEP) for ventral hernias: Short-term results from a single centre. AB - Introduction: There has been a surge of innovative procedures in the field of abdominal wall hernias. Works of pioneers such as Dr. Yuri Novitsky, Dr. Jorge Daes and Dr. Igor Belyansky have started a new era in the field of hernia surgery. Conventional and popular surgeries for ventral hernias are open onlay mesh hernioplasty, open retromuscular mesh hernioplasty (Rives-Stoppa procedure) and laparoscopic intraperitoneal mesh hernioplasty. Evidence seems to suggest that retromuscular mesh hernioplasty has advantages over other procedures regarding recurrence and surgical site occurrences. An alternative strategy has been developed for this setting where a mesh is placed in retromuscular space by minimal access technique of the extended Totally Extraperitoneal approach (eTEP). Methods: We have retrospectively analysed the data of 21 patients who underwent an eTEP procedure with a minimum follow-up of 2 months. Their data were analysed for operative details, intra-operative and post-operative complications. Results: For a total of 21 patients, we have recorded a total of two surgical site occurrences (1 seroma and 1 linea alba dehiscence) and one recurrence. One patient had chronic pain. There was no surgical site infection. Conclusion: Judging from our short-term results, we suggest that the eTEP technique can be adapted in centres with advanced laparoscopic skills with the careful patient selection. PMID- 29794362 TI - Clip-stone and T clip-sinus: A clinical analysis of six cases on migration of clips and literature review from 1997 to 2017. AB - Introduction: With the development of laparoscopic skills, the laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) has become the standard surgical procedure for choledocholithiasis. We usually use Hem-o-lok clips to control cystic duct and vessels, which is safe on most occasions and has few perioperative complications such as major bleeding, wound infection, bile leakage, and biliary and bowel injury. However, a rare complication of post-cholecystectomy clip migration (PCCM) increases year by year due to the advancement and development of LC, CBD exploration as well as the wide use of surgical ligation clips. Materials and Methods: Six patients whose clips are found dropping into CBD or forming T-tube sinus after laparoscopic surgery in our department. Results: Six patients whose clips are found dropping into CBD (clip-stone) (3/6) or forming T-tube sinus (T clip-sinus) (3/6) after LCBDE or LC. Conclusions: PCCM is a rare but severe complication of LCBDE. A pre-operative understanding of bile duct anatomy, the use of the minimum number of clips and the harmonic scalpel during the surgeries is necessary. Considering clip-stone or clip-sinus in the differential diagnosis of patients with biliary colics or cholangitis after LCBDE even years after surgery, the detailed medical history and pre-operative examination are inevitable, especially for these patients who had undergone LCBDE. PMID- 29794363 TI - The debate between use and cost of technology is on-going! PMID- 29794364 TI - Laparoscopic splenectomy for large splenic pseudocyst: A rare case report and review of literature. AB - Laparoscopic splenectomy is gaining popularity due to less morbidity and minimal operative complications. Nowadays, laparoscopic splenectomy is the approach of choice for both benign and malignant diseases of the spleen. Splenic pseudocyst due to non-traumatic cause has been very rarely reported in literature. We report an interesting case of a rare large splenic pseudocyst without a history of previous abdominal trauma, treated successfully by laparoscopic technique and discuss literature for the same. PMID- 29794365 TI - Per-operative modified rigid cholangioscopy for removal of intrahepatic stones associated with choledochal cyst in children. AB - Introduction: Choledochal cyst (CDC) is often associated with intrahepatic stones (IHSs) in children which necessitate their removal during excision. The endoscopic equipment needed for their clearance such as paediatric flexible cholangioscope and other advanced modalities are not freely available in resource poor setups. We describe per-operative modified rigid cholangioscopy using rigid paediatric cystoscope for stone removal during open CDC excision. Methods: All children with CDC presenting with IHSs between January 2015 and December 2017 were included in the present study. IHSs were diagnosed by ultrasound/magnetic resonance cholangiopancreatography (MRCP). In these patients, after cyst excision by open technique, a 9 Fr paediatric cystoscope with 4 Fr working channel was inserted into the common hepatic duct for visualisation and clearance of stones from (intrahepatic bile ducts). Follow-up was done using liver function tests, ultrasound and MRCP (if needed). Patients underwent three monthly liver function test and ultrasound and if needed MRCP. Results: Six cases of CDC presenting with IHS were managed, and one case with post-R-en-Y IHS was treated with this technique. Rigid paediatric cystoscope with working channel and forceps was used. All cases were successfully managed, and one case was found to have intrahepatic duct stenosis was dilated. Conclusion: Per-operative rigid endoscopy using paediatric cystoscope is an easily available tool in most of the setups for the management of IHS associated with CDC in children. PMID- 29794366 TI - Early recurrence after laparoscopic radical cholecystectomy in a patient with gallbladder cancer. AB - Laparoscopic radical cholecystectomy for gallbladder cancer (GBC) has been performed at various oncology centres reporting its technical feasibility. Considering GBC an aggressive malignancy, laparoscopic radical cholecystectomy should be dealt with caution. We recently encountered a case of carcinoma gallbladder who underwent laparoscopic radical cholecystectomy elsewhere and presented with early recurrence. The patient's records were evaluated and he underwent re-resection. Hereby, we discuss the factors that could lead to early recurrence after laparoscopic radical cholecystectomy and measures that can be taken to prevent it. PMID- 29794367 TI - 5-Methylmellein is a novel inhibitor of fungal sirtuin and modulates fungal secondary metabolite production. AB - Sirtuin is an NAD+-dependent histone deacetylase that is highly conserved among prokaryotes and eukaryotes. Sirtuin deacetylates histones and non-histone proteins, and it is involved in fungal growth and secondary metabolite production. Here, we screened 579 fungal culture extracts that inhibited the histone deacetylase activity of Sirtuin A (SirA), produced by the fungus Aspergillus nidulans. Eight fungal strains containing three Ascomycota, two Basidiomycota and three Deuteromycetes produced SirA inhibitors. We purified the SirA inhibitor from the culture broth of Didymobotryum rigidum JCM 8837, and identified it as 5-methylmellein-a known polyketide. This polyketide and its structurally-related compound, mellein, inhibited SirA activity with IC50 of 120 and 160 MUM, respectively. Adding 5-methylmellein to A. nidulans cultures increased secondary metabolite production in the medium. The metabolite profiles were different from those obtained by adding other sirtuin inhibitors nicotinamide and sirtinol to the culture. These results indicated that 5 methylmellein modulates fungal secondary metabolism, and is a potential tool for screening novel compounds derived from fungi. PMID- 29794368 TI - Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology. AB - Living organisms enantioselectively employ L-amino acids as the molecular architecture of protein synthesized in the ribosome. Although L-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of D-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of D-amino acids. In contrast, archaea and eukaryotes are thought generally to synthesize only two kinds of D-amino acids: D-serine and D aspartate. In mammals, D-serine is critical for neurotransmission as an endogenous coagonist of N-methyl D-aspartate receptors. Additionally, D-aspartate is associated with neurogenesis and endocrine systems. Furthermore, recognition of D-amino acids originating in bacteria is linked to systemic and mucosal innate immunity. Among the roles played by D-amino acids in human pathology, the dysfunction of neurotransmission mediated by D-serine is implicated in psychiatric and neurological disorders. Non-enzymatic conversion of L-aspartate or L-serine residues to their D-configurations is involved in age-associated protein degeneration. Moreover, the measurement of plasma or urinary D-/L-serine or D-/L-aspartate levels may have diagnostic or prognostic value in the treatment of kidney diseases. This review aims to summarize current understanding of D amino-acid-associated biology with a major focus on mammalian physiology and pathology. PMID- 29794369 TI - Transducin beta-like 1, X-linked and nuclear receptor co-repressor cooperatively augment the ligand-independent stimulation of TRH and TSHbeta gene promoters by thyroid hormone receptors. AB - Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus-pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHbeta gene promoters by thyroid hormone receptors (TR) in cell culture systems. We herein investigated whether TBL1X affects the unliganded TR mediated stimulation of the promoter activities of genes negatively regulated by T3 in cooperation with N-CoR. In a hypothalamic neuronal cell line, the unliganded TR-mediated stimulation of the TRH gene promoter was significantly enhanced by co-transfected TBL1X, and the co-transfection of TBL1X with N-CoR further enhanced promoter activity. In contrast, the knockdown of endogenous Tbl1x using short interfering RNA significantly attenuated the N-CoR-mediated enhancement of promoter activity in the presence of unliganded TR. The co transfection of N365Y or Y458C, TBL1X mutants identified in CeH patients, showed impaired co-activation with N-CoR for the ligand-independent stimulation of the TRH promoter by TR. In the absence of T3, similar or impaired enhancement of the TSHbeta gene promoter by the wild type or TBL1X mutants, respectively, was observed in the presence of co-transfected TR and N-CoR in CV-1 cells. These results suggest that TBL1X is needed for the full activation of TRH and TSHbeta gene promoters by unliganded TR. Mutations in TBL1X may cause CeH due to the impaired up-regulation of TRH and/or TSHbeta gene transcription despite low T3 levels. PMID- 29794370 TI - Collagen-enriched serpiginous skin lesion in a cat resembling the linear form of localized scleroderma in humans. AB - Localized scleroderma (LS) is a sclerotic skin disorder rarely reported in the veterinary literature. We herein report the first case of a linear LS-like skin lesion in a cat. A 1-year-old castrated male Himalayan cat was presented with a 1 month history of an alopecic, indurated, serpiginous, branched skin lesion on the dorsal cervical to scapular area. The cat had no history of trauma, although a topical spot-on endectocide had been applied near the lesion. Histopathological examination revealed a focal area of hyperplastic dermal collagen with the absence of pilosebaceous units. The cutaneous lesion remained unchanged during a 2-year follow-up period. Clinical and histopathological similarities of this skin lesion with those of the linear form of LS in humans were considered. PMID- 29794371 TI - Sarcomatoid mesothelioma of tunica vaginalis testis in the right scrotum of a dog. AB - A 12-year-old intact male Welsh Corgi was presented with enlargement of the right scrotum. Both testicles were surgically removed and histopathologically examined. On gross examination, white nodules were found in the epididymis and ductus deferens. Histopathologically, the nodules developed continuously from the tunica vaginalis testis of the right scrotum and consisted of spindle-shaped neoplastic cells that invaded the surrounding tissue. Immunohistochemically, the neoplastic cells were diffusely positive for vimentin, cytokeratin and Wilms tumor-1 (WT-1). Based on these findings, the tumor was diagnosed as sarcomatoid mesothelioma. The dog presented with respiratory distress 122 days after surgery and clinical examination found multiple metastatic lesions in the lung, abdominal lymph nodes and peritoneum. The dog died 144 days after surgery due to disease progression. PMID- 29794372 TI - Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats. AB - Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization. PMID- 29794374 TI - Primary Cardiac Diffuse Large B-Cell Lymphoma. PMID- 29794373 TI - The characteristics of a porcine mitral regurgitation model. AB - The porcine mitral regurgitation (MR) model is a common cardiovascular animal model. Standardized manufacturing processes can improve the uniformity and success rate of the model, and systematic research can evaluate its potential use. In this study, 17 pigs were divided into an experimental group (n=11) and a control group (n=6). We used a homemade retractor to cut the mitral chordae via the left atrial appendage to establish a model of MR; the control group underwent a sham surgery. The model animals were followed for 30 months after the surgery. Enlargement and fibrosis of the left atrium were significant in the experimental group compared with those in the control group, and left atrial systolic function decreased significantly. In addition, model animals showed preserved left ventricular systolic function. There were no differences in left atrial potential or left ventricular myocardial fibrosis between the two groups. Atrial fibrillation susceptibility in the experimental group was higher than that in the control group. Our method enables the simple and effective production of a MR model with severe reflux that can be used for pathophysiological studies of MR, as well as for the development of preclinical surgical instruments and their evaluation. This model could also be used to study atrial fibrillation and myocardial fibrosis but is not suitable for studies of heart failure. PMID- 29794375 TI - Learning Curve for Transcatheter Aortic Valve Implantation Under a Controlled Introduction System - Initial Analysis of a Japanese Nationwide Registry. AB - BACKGROUND: The introduction of transcatheter aortic valve implantation (TAVI) into Japan was strictly controlled to optimize patient outcomes. The goal of this study was to assess if increasing experience during the introduction of this procedure was associated with outcomes.Methods and Results:The initial 1,752 patients registered in the Japanese national TAVI registry were included in the study. The association between operator procedure number and incidence of the early safety endpoint at 30 days (ESE30) as defined in the Valve Academic Research Consortium-2 consensus document was evaluated. Patients were divided into 4 groups by quartiles of procedure count (Groups I-IV in order of increasing number of procedures). Median patient age was 85 years, and 30.5% were male. The 30-day mortality rate was 1.4% (n=24), and 78 patients (7.9%) experienced 95 ESE30. Among the variables included in the model, ESE30 was associated with non transfemoral approach (P=0.004), renal dysfunction (Cr >2.0 mg/dL) (P=0.01) and NYHA class III/IV (P=0.04). ESE30 incidence was not significantly different between Groups I-III and Group IV. Spline plots demonstrated that experience of 15-20 cases in total was needed to achieve a consistent low risk of ESE30. CONCLUSIONS: Increasing experience was associated with better outcomes, but to a lesser degree than in previous reports. Our findings suggested that the risks associated with the learning curve process were appropriately mitigated. PMID- 29794376 TI - Diastolic Tricuspid Regurgitation Related to Atrial Systole With a Bileaflet Mechanical Valve. PMID- 29794378 TI - Effect of Geranylgeranyl Pyrophosphate Synthase on Hypoxia/Reoxygenation-Induced Injury in Heart-Derived H9c2 Cells. AB - Recent studies have revealed that geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme involved in protein prenylation, plays a critical role in postnatal heart growth by regulating cardiomyocyte size. However, the role of GGPPS in myocardial ischemia/reperfusion (MIR) injury is still not clear. The objective of this work was to investigate the effect of GGPPS on MIR injury in H9c2 cells subjected to hypoxia/reoxygenation (HR) to mimic MIR. Prior to HR, the cells were transfected with GGPPS, shGGPPS, or shGFP. The results showed that cell viability was reduced, and cell injury and cell apoptosis were increased as a result of overexpression of GGPPS. Knockdown of GGPPS improved cell viability, and decreased cell injury and cell apoptosis. Furthermore, overexpression of GGPPS increased Rac1 activity and ROS generation, while GGPPS silencing decreased Rac1 activity and ROS generation. Based on these findings, we propose that the alteration of GGPPS expression changed the Rac1 activity and ROS production, and finally led to the different severity of HR-induced injury in H9c2 cells. These findings indicate that GGPPS might be a potential target in preventing H9c2 cells from HR-induced injury. PMID- 29794377 TI - Clinical Characteristics and Mid-Term Outcomes of Non-Elderly Obese Patients with Acute Decompensated Heart Failure in Japan. AB - Obesity is a well-known risk factor for cardiovascular diseases including heart failure (HF). However, some literatures suggested better clinical outcomes in obese patients with HF. Since higher body mass index (BMI) levels of HF patients were significantly associated with younger age, the impact of obesity on clinical outcomes in non-elderly HF patients should be elucidated.Consecutive 155 non elderly acute decompensated HF patients (< 60-year-old) who admitted to our institution between 2009 and 2013 were included. Those patients were divided into the two groups according to the BMI: the obesity group (BMI >= 25 kg/m2, n = 81) and the non-obesity group (BMI < 25 kg/m2, n = 74). The primary composite outcome of this study was defined as re-admission due to HF and all-cause death.The primary composite outcome was less frequently observed in the obesity group as compared with the non-obesity group (Hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.26-0.95, P = 0.03). Re-admission due to HF was significantly less in the obesity group than in the non-obesity group (HR 0.44, 95% CI 0.23-0.86, P = 0.02), whereas all-cause death was not significantly different between the groups (P = 0.44).The mid-term outcomes in non-elderly HF patients with obesity were better as compared with non-elderly HF patients without obesity, which supports obesity paradox in this specific population. PMID- 29794379 TI - Combined Evaluation of the Plasma Arginine Vasopressin and Noradrenaline Levels May be a Useful Predictor of the Prognosis of Patients with Acute Decompensated Heart Failure. AB - Few data exist regarding the association of plasma arginine vasopressin (AVP) and noradrenaline (NA) levels with subsequent cardiac events in acute decompensated heart failure (ADHF) patients. We measured plasma AVP and NA levels in ADHF patients on admission. In the follow-up (median: 487 days) of 291 patients, 41 cardiac events (cardiac death or re-hospitalization due to HF) were documented. The plasma AVP (26.4 versus 15.5 pg/mL, P = 0.014) and plasma NA (2347 versus 1524 pg/mL, P = 0.007) levels in the cardiac events group were significantly higher than those in the non-cardiac events group. The multivariable hazard ratios (HR) (95% confidence intervals [CI]) in the first tertile (1T) versus the third tertile (3T) of plasma AVP and NA levels were 2.97 (1.06-8.32) and 3.34 (1.21-9.26) for cardiac events, respectively. Group High (3T of combined AVP and NA) had a significantly higher incidence of cardiac events than Group Low (1T of combined groups) (HR: 3.50, 95% CI: 1.17-10.42, P = 0.017). Similarly, the relative risk ratio of cardiac events according to this stratification was more than that of plasma AVP or NA level alone (3.51, 2.65, and 2.95). Higher levels of plasma AVP and NA measured on admission may be associated with the incidence of cardiac events. Combined evaluation of these two parameters may be useful for assessing the prognosis of ADHF survivors. PMID- 29794380 TI - Successful Treatment of Protein-Losing Enteropathy and Plastic Bronchitis by Biphasic Cuirass Ventilation in a Patient with Failing Fontan Circulation. AB - We present a 16-year-old male patient with hypoplastic left heart syndrome who developed protein-losing enteropathy (PLE) and plastic bronchitis (PB) after a Fontan operation. He received medical therapies, including albumin infusion, unfractionated heparin, and high-dose anti-aldosterone therapy but could not obtain clinical relief. Biphasic cuirass ventilation (BCV) led to expectoration of bronchial casts and prompt resolution of PB. Notably, clinical symptoms related to PLE were dramatically improved after starting BCV. A brief period of BCV increased stroke volume from 26+/-1.4 to 39+/-4.0 mL. This case suggests that BCV could be an effective treatment for PLE in patients with failing Fontan circulation. PMID- 29794381 TI - Catecholamine-Induced Senescence of Endothelial Cells and Bone Marrow Cells Promotes Cardiac Dysfunction in Mice. AB - Previous studies have suggested that cellular senescence plays a central role in the progression of pathologic changes in the failing heart. It is well known that the sympathetic nervous system is activated in patients with heart failure, and this change is associated with poor clinical outcomes. Sympathetic activation increases the levels of various catecholamines, such as epinephrine and norepinephrine, but the contribution of these catecholamines to cellular senescence associated with heart failure remains to be determined. We found that catecholamine infusion induced senescence of endothelial cells and bone marrow cells, and promoted cardiac dysfunction in mice. In C57BL/6NCr mice, the continuous infusion of isoproterenol-induced cardiac inflammation and cardiac dysfunction. Expression of p53, a master regulator of cellular senescence, was increased in the cardiac tissue and bone marrow cells of these mice. Suppression of cellular senescence by genetic deletion of p53 in endothelial cells or bone marrow cells led to improvement of isoproterenol-induced cardiac dysfunction. In vitro studies showed that adrenergic signaling increased the expression of p53 and adhesion molecules by endothelial cells and macrophages. Our results indicate that catecholamine-induced senescence of endothelial cells and bone marrow cells plays a pivotal role in the progression of heart failure. Suppression of catecholamine-p53 signaling is crucial for inhibition of remodeling in the failing heart. PMID- 29794382 TI - Cardiomyopathy Phenotypes and Pregnancy Outcomes with Left Ventricular Noncompaction Cardiomyopathy. AB - Little is known about pregnancies of left ventricular noncompaction cardiomyopathy (LVNC), much less cases in which LVNC was definitively diagnosed prepregnancy. We report the cases of three pregnant Japanese women definitively diagnosed with LVNC prepregnancy. Case 1 presented LVNC with restrictive phenotype. Her pregnancy was terminated due to exacerbated pulmonary hypertension and low output status at 30 weeks' gestation. Case 2 presented isolated LVNC with nonsustained ventricle tachycardia. A cesarean section was performed at 36 weeks' gestation because of placenta previa. Case 3 presented dilated LVNC. Labor induction was performed because of decreased left ventricular ejection fraction, leading to a vaginal delivery at 37 weeks' gestation. In all cases, no thromboembolic event was identified during pregnancy; two patients received anticoagulants. We reviewed all English-literature cases of pregnant women definitively diagnosed with LVNC prepregnancy to analyze causes of adverse pregnancy outcomes and the necessity of anticoagulation. Four of the six pregnancies identified were terminated due to exacerbated cardiomyopathy phenotypes and not complications due to noncompaction itself, resulting in three cases' preterm deliveries. No thromboembolic event was identified by maintenance of the anticoagulation strategy determined prepregnancy. In pregnancies with LVNC, the possibility of a severe cardiac event and the indications for termination of the pregnancy can depend on the cardiomyopathy phenotypes, not noncompaction itself. Anticoagulation only because of the pregnancy itself may be redundant. In the management of LVNC during pregnancy, close monitoring of the condition of different phenotypes and reassessment of the necessity of anticoagulation can contribute to the pregnancy outcome. PMID- 29794383 TI - Myocardial Injury Caused by Severe Blow: Importance of Carefulness in Accurate Diagnosis. AB - Blunt chest trauma may lead to cardiac involvement such as myocardial contusion, coronary artery dissection, cardiac rupture, or myocardial infarction. Early detection and treatment of complications such as these are essential. We describe a case status post collision with an iron ball and discuss how to detect myocardial infarction. We emphasize the importance of careful interview, physical examination, and electrocardiogram even in seemingly healthy patients. A severe blow, such as that described, can impair coronary artery flow and may potentially cause myocardial infarction. PMID- 29794384 TI - Coronary Artery Perforation During Percutaneous Coronary Intervention in a Patient with a Prior Modified Bentall Procedure. AB - The Bentall procedure is a surgical technique for an ascending aortic or aortic aneurysm in combination with valve disease. A well-known uncommon complication of after the Bentall procedure is coronary artery stenosis related to coronary anastomosis of an interposed graft. We report on a 73-year-old woman who presented with heart failure secondary to graft stenosis of the right coronary artery 6 months after undergoing a modified Bentall procedure. Percutaneous coronary intervention (PCI) was performed and type II coronary artery perforation occurred during PCI of the right coronary artery. We used a perfusion balloon and achieved hemostasis successfully. We report a case of coronary artery perforation that was treated with perfusion balloon during PCI in a patient with a prior modified Bentall procedure. In addition, we present a case series of PCI for ostial coronary stenosis after the Bentall procedure. PMID- 29794385 TI - A Case of Pulmonary Hypertension Associated with Idiopathic Hypereosinophilic Syndrome. AB - Hypereosinophilic syndrome (HES) is characterized by multi-organ damage that is associated with tissue hypereosinophilia. A persistently elevated eosinophilic count is also required for the diagnosis of HES. Although HES affects various organs, damage to pulmonary artery is rarely reported. We present a case of a 39 year-old man who was diagnosed with pulmonary hypertension (PH) associated with idiopathic HES. Although the pulmonary arterial hypertension specific drugs including intravenous epoprostenol could not control his PH, corticosteroid was effective for both hypereosinophilia and PH. Our case suggests the importance of steroid therapy as well as specific drugs for pulmonary arterial hypertension in the treatment of PH associated with HES. PMID- 29794386 TI - What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy? AB - Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large scale prospective trial with optimal patient selection and optimal device setting is warranted. PMID- 29794387 TI - Occurrence of Potentially Lethal Arrhythmia due to Sudden Exposure of an Overt Accessory Pathway 8 Years After Catheter Ablation of a Concealed Accessory Pathway. AB - Although the efficacy of catheter ablation of the accessory pathway (AP) has been established, there are subgroups of APs with an intermittent conduction property, which is sometimes difficult to diagnose accurately. A 57-year-old man with a history of catheter ablation was referred to our clinic due to frequent faintness. He had undergone concealed AP ablation 8 years previously and bilateral circumferential pulmonary vein isolation (CPVI) 6 years previously. During regular electrocardiogram monitoring, it was suggested that irregular wide QRS tachycardia, which was considered to be atrial fibrillation with antegrade AP conduction, was the cause of the present symptoms. In the present electrophysiological study, we noticed a residual antegrade AP in the left lateral wall that was not observed during the previous session. We achieved abolition of overt accessory conduction, bilateral CPVI, and superior vena cava isolation with several radiofrequency applications without any recurrence. We also confirmed the absence of dormant conduction in the AP and the left atrium-PV connection with 20 mg adenosine triphosphate. This case demonstrated the possibility of sudden exposure of overt AP conduction late after catheter ablation of the concealed AP and the importance of confirming the absence of dormant conduction by means of adenosine triphosphate, which has the potential benefit of revealing latent AP conduction. PMID- 29794388 TI - Spontaneous Coronary Artery Dissection Accompanied with Antiphospholipid Syndrome and Leukemia. AB - We report a rare spontaneous coronary artery dissection (SCAD) case accompanied by antiphospholipid syndrome (APS) and leukemia which was treated successfully with drug-eluted stents (DES) implantation. This young SCAD patient was initially diagnosed of acute myocardial infarction (AMI); however, except for 6 pack-years of smoking, there were no risk factors or family history of coronary artery disease. Subsequently, we screened other clinical status like autoimmune diseases and finally found APS. In general, APS was associated with thromboembolism events, not coronary artery dissection. Our case indicated that SCAD could be a rare manifestation of APS which should draw our attention. In addition, our bail out therapy acquired the expected effect. PMID- 29794389 TI - Exacerbated Peri-Stent Contrast Staining on Serial Angiography and Optical Coherence Tomography After Platinum-Chromium Everolimus-Eluting Stent Implantation for Infrapopliteal Artery Lesions. AB - Unlike coronary arteries, little is known about peri-stent contrast staining (PSS) formation after drug-eluting stent (DES) implantation for infrapopliteal arteries. Herein, we report exacerbated PSS assessed by serial angiography and optical coherence tomography (OCT) after platinum-chromium everolimus-eluting stent (PtCr-EES) implantation for infrapopliteal artery lesions. A 68-year-old women with recurrent left critical limb ischemia was admitted to our hospital. Standard endovascular techniques were performed for the popliteal artery (POP) and tibioperoneal trunk (TPT), but residual stenosis occurred. Therefore, a 4.0 * 38-mm PtCr-EES was placed from the distal POP to TPT using OCT guidance. Ten months later, the patient was referred to our hospital due to recurrent left leg rest pain. Angiography showed severe stenosis from the distal POP to the proximal site of the stent, and diffuse in-stent restenosis (ISR). At the ISR site, stent fracture and compression were observed and vessel evaginations were newly detected on OCT. At that time, good angiographic results were obtained by conventional balloon angioplasty alone. At 6 months follow-up, recurrence of ISR was suspected on duplex ultrasonography. Angiography showed no significant ISR, but PSS had markedly exacerbated from focal type to segmental type. OCT showed exacerbated vessel evagination and in-stent thrombus. The incidence and clinical impact of PSS after DES implantation in infrapopliteal artery lesions remain unclear; therefore, careful follow-up may be needed in such cases. PMID- 29794390 TI - Change of Exhaled Acetone Concentration Levels in Patients with Acute Decompensated Heart Failure. AB - Exhaled acetone concentration is one of the expected compounds to be a breath biomarker in heart failure. However, it has not been clarified how exhaled acetone concentration changes in clinical course of heart failure.To investigate whether exhaled acetone concentration changes after treatment in acute decompensated heart failure (ADHF).This study included 19 patients with ADHF (ADHF group) and eight patients with stable heart failure (control group). Exhaled acetone was collected from these patients, and the concentration was measured with gas chromatography.The ADHF group had higher heart rates (P = 0.046), higher New York Heart Association class (P < 0.001), higher levels of brain natriuretic peptide (P = 0.026), blood total ketone bodies (P = 0.015), and exhaled acetone concentration (P < 0.001), compared with the control group. In ADHF group, exhaled acetone concentration significantly decreased after treatment (median: 2.40 versus 0.92 ppm, P < 0.001). However, in the control group, exhaled acetone concentration did not significantly change (median: 0.73 versus 0.49 ppm, P = 0.141).In these preliminary findings, exhaled acetone concentration in patients with ADHF drastically decreased by treatment. Serial exhaled acetone measurement might be useful to evaluate the course of ADHF. PMID- 29794391 TI - Importance of Early Diagnosis of Cardiac Sarcoidosis in Patients with Complete Atrioventricular Block. AB - Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 +/- 2.8 versus -32.4 +/- 3.9%, P < 0.0001; -11.1 +/- 16.0 versus 161.8 +/- 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 +/- 10.7 versus 37.0 +/- 9.3%, P = 0.0128; 63.0 +/- 46.4 versus 458.8 +/- 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function. PMID- 29794392 TI - Effectiveness of Nitroglycerin in Managing Subacute Lung Bleeding Induced by Balloon Pulmonary Angioplasty. AB - Lung bleeding (LB) and hemoptysis is a common but life-threating complication of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension. LBs related to BPA mostly occur acutely during BPA session. Therefore, it can usually be managed with occlusion balloon or other catheter based approaches. While LB also develops subacutely after BPA session, the pharmacological option to subacute LB is currently limited. Here, we present a case of subacute LB which can be managed with intravenous administration of nitroglycerin. Nitrate mediated venous dilation can be an effective therapeutic option in managing LB and hemoptysis after BPA session. PMID- 29794393 TI - Sequential Grafting of in Situ Skeletonized Left Internal Mammary Artery to the Left Coronary System. AB - Sequential grafting may be an effective way to maximize the benefits of the left internal mammary artery (LIMA) conduit. Despite increasing clinical application, the strategy of sequential LIMA grafting has not been proven its superiority. This single-center retrospective study aimed to evaluate the in-hospital and mid term outcomes of sequential grafting of in situ skeletonized LIMA to the left coronary system.According to the use of sequential or separate LIMA grafting, 1505 eligible patients were assigned to a sequential group (n = 230) and a control group (n = 1275). According to sequential LIMA graft configurations, patients with sequential LIMA grafting were divided into a DOM subgroup (n = 113) and a DLAD subgroup (n = 117). The clinical outcomes and LIMA graft patency were investigated and compared.Sequential LIMA grafting compared with separate LIMA grafting was not an independent predictor either of in-hospital adverse events or follow-up survival free from repeat revascularization during the follow-up period of 32.4 +/- 8.5 months. Sequential LIMA grafting had similar LIMA graft patency with separate LIMA grafting (99.5% of 1st sequential sites and 97.7% of 2nd sites versus 98.2% of LIMA-LAD grafts) at 32.3 +/- 8.5 months after coronary artery bypass grafting (CABG) surgery. Additionally, the two subgroups received similar mid-term clinical outcomes and graft patency of LIMA segments.Sequential grafting of in situ skeletonized LIMA to the left coronary system resulted in excellent clinical outcomes and graft patency. The two sequential LIMA graft configurations received similar clinical outcomes and graft patency. PMID- 29794395 TI - Neopterin as a Marker of In-Stent Restenosis: to Have or Have Not. PMID- 29794394 TI - Endovascular Embolization of Coronary Artery-Pulmonary Artery Fistulas with Double Coronary Aneurysms. AB - A 75-year-old woman with chest discomfort and a continuous murmur was admitted to our hospital. During noninvasive examination, computed tomography angiography showed a coronary artery-pulmonary artery fistula with double giant coronary aneurysms (one was 42 mm* 32 mm* 32 mm, and the other was 25 mm* 20 mm* 17 mm) arising from the proximal part of the left anterior descending (LAD) artery. Stress myocardial scintigraphy showed ischemia at the LAD area. Given her frailty, the heart team, including cardiac surgeons, judged that surgical treatment would be difficult. Thus, endovascular embolization for the abnormal vessels was selected. After coronary angiography, two coronary aneurysms were embolized by 53 coils, and the feeding artery was embolized by two coils and one Amplatzer Vascular Plug 4TM. A small pulmonary artery fistula remained after the procedures; thus, additional embolization was performed 3 months after the index procedure. Thereafter, angiography showed no flow into the aneurysms, and her symptoms improved.Endovascular embolization might be an effective treatment to achieve aneurysm occlusion in patients at high risk for surgical treatment. Although the present case had double coronary aneurysms with a large feeder vessel, the combination procedure of coils and vascular plug was able to embolize this abnormal vessel. PMID- 29794396 TI - [The 39th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (The 42nd Survey in 2016)]. AB - This survey was performed to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2016 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 977 institutions among 1,235 to which the questionnaire had been sent. Nine cases of adverse reactions were reported. A total of 1,052,650 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 0.9. No case of deficient products was reported. PMID- 29794397 TI - Prefrontal cortex activity during swallowing in dysphagia patients. AB - Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food. PMID- 29794398 TI - In vitro and clinical evaluation of optical coherence tomography for the detection of subgingival calculus and root cementum. AB - This study evaluated the effectiveness of swept-source optical coherence tomography (ss-OCT) for detecting calculus and root cementum during periodontal therapy. Optical coherence tomography (OCT) images were taken before and after removal of subgingival calculus from extracted teeth and compared with non decalcified histological sections. Porcine gingival sheets of various thicknesses were applied to the root surfaces of extracted teeth with calculus and OCT images were taken. OCT images were also taken before and after scaling and root planing (SRP) in human patients. In vitro, calculus was clearly detected as a white-gray amorphous structure on the root surface, which disappeared after removal. Cementum was identified as a thin, dark-gray layer. The calculus could not be clearly observed when soft tissues were present on the root surface. Clinically, supragingival calculus and cementum could be detected clearly with OCT, and subgingival calculus in the buccal cervical area of the anterior and premolar teeth was identified, which disappeared after SRP. Digital processing of the original OCT images was useful for clarifying the calculus. In conclusion, ss-OCT showed potential as a periodontal diagnostic tool for detecting cementum and subgingival calculus, although the practical applications of subgingival imaging remain limited. PMID- 29794399 TI - Effect of orthodontic forces on the osteogenic differentiation of human periodontal ligament stem cells. AB - The purpose of this study was to evaluate the effects of orthodontic forces (OF) on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). The experimental sample consisted of 6 premolars extracted from 2 patients. After application of OF for 1 month, the hPDLSCs were separated from the primary cultured PDL cells using magnetic-activated cell sorting. The cell proliferation rate was assessed using a 3-[45-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. The hPDLSCs were cultured in osteogenic medium, and the osteogenic differentiation was analyzed on day 7 and 14 using alkaline phosphatase staining and reverse transcription polymerase chain reaction analyses. The gene expression level of osteogenic markers and angiogenic markers were measured and normalized. The results showed that the application of OF increased the proliferation rates, the expression of osteogenic factors, and the expression of angiogenic factors of hPDLSCs. These findings suggest that OF can serve as a potent positive modulator of proliferation and osteogenic differentiation of hPDLSCs. PMID- 29794400 TI - Effect of Atrial Fibrillation on the Incidence and Outcome of Osteoporotic Fracture - A Nationwide Population-Based Study. AB - BACKGROUND: Both atrial fibrillation (AF) and osteoporosis are common in older adults. The purpose of this study was to investigate whether comorbid AF in patients with osteoporosis is associated with fracture incidence, or death after fracture.Methods and Results:From the National Health Insurance Service database of Korea, we selected 31,778 patients with osteoporosis. During a median follow up of 48 months, the incidence of bone fractures was higher in AF patients than in non-AF patients (3.20 vs. 2.18 per 100 person-years), respectively. In the multivariate Cox regression analysis, AF was associated with fracture independently of other risk factors with an adjusted hazard ratio (HR) of 1.21 (95% confidence interval [CI], 1.02-1.41; P=0.031). The mortality rate after fracture was significantly higher in AF patients than it was in non-AF patients (adjusted HR, 1.92; 95% CI, 1.35-3.27; P=0.016). After propensity score-matching, AF was consistently associated with a higher risk of osteoporotic fracture and subsequent death after fracture. In AF patients, older age, female sex, being underweight (body mass index <18.5 kg/m2), decreased physical activity (exercise <3 times/week), history of stroke or transient ischemic attack, thiazide use, sedative use, and higher CHADS2(>=2 points) or CHA2DS2-VASc (>=2 points) scores were associated with the incidence of fractures. CONCLUSIONS: Comorbid AF in patients with osteoporosis was associated with an increased risk of bone fracture and death after fracture. PMID- 29794401 TI - Propensity Score Matched Analysis of Mechanical vs. Bioprosthetic Valve Replacement in Patients With Previous Stroke. AB - BACKGROUND: This study compared the long-term outcomes of prosthetic heart valve replacement with mechanical or bioprosthetic valves in patients with prior stroke.Methods and Results:In total, 1,984 patients with previous stroke who had received valve replacement between 2000 and 2011 were identified using the Taiwan National Health Insurance Research Database. Propensity score matching analysis was used. Ultimately, 547 patients were extracted from each group and were eligible for analysis. On survival analysis, the risks of all-cause mortality and recurrence of stroke were similar. The incidence of major bleeding was greater in the mechanical valve group than in the bioprosthetic valve group (P=0.040), whereas no difference was observed in re-do valve surgery. On subgroup analysis, the bioprosthetic valve was favored for older age (>=60 years) and previous gastrointestinal (GI) bleeding patients. The mechanical valve, however, was favored for younger patients (<60 years). CONCLUSIONS: In patients with previous stroke, bioprosthetic valves had a lower incidence of complications connected to major bleeding than did the mechanical valves. Survival and stroke recurrence rates, however, did not differ between the 2 groups. We recommend bioprosthetic valves for patients >60 years or who have a history of GI bleeding. PMID- 29794402 TI - Effects of Carperitide on Degree of Pulmonary Congestion in Treatment of Acute Heart Failure. AB - BACKGROUND: Carperitide is used to treat acute heart failure (AHF) in Japan. Whether the degree of pulmonary congestion is associated with the effects of carperitide on AHF is unclear.Methods and Results:We retrospectively investigated the in-hospital outcomes and prognoses of 742 patients hospitalized for AHF between February 2015 and January 2017 and classified them into carperitide and non-carperitide groups, stratified according to the degree of pulmonary congestion. The median follow-up duration after admission was 231 days. In patients with moderate-severe pulmonary congestion, the rate of remaining congestion on chest X-ray at discharge was lower in the carperitide group than in the non-carperitide group (1.5% vs. 9.0%, P=0.004). Also, the carperitide group had significant reduction in a composite of all-cause death or rehospitalization for HF (adjusted hazard ratio, 0.62; 95% CI: 0.41-0.93; P=0.02). In patients with no-mild pulmonary congestion, carperitide was not associated with better clinical outcome. CONCLUSIONS: In the treatment of AHF with moderate-severe pulmonary congestion, carperitide is associated with more effective decongestion in the short term and better prognosis in the long term. PMID- 29794403 TI - BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Autophagy in Osteoarthritic Rats. AB - Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome related molecules. These findings indicate that BST106 protects against OA induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux. PMID- 29794404 TI - Mongolian Medicine echinops prevented postmenopausal osteoporosis and induced ER/AKT/ERK pathway in BMSCs. AB - Hormone replacement medicine such as traditional Chinese medicine has proven to be effective in decreasing the risk of osteoporosis. Mongolian medicine echinops prevents osteoporosis, but its mechanism remains unclear. In this study, we explored the mechanism underlying echinops prevents and treats postmenopausal osteoporosis. Osteoporosis model was established by ovariectomy in rats. Rats were treated to Echinops (16.26, 32.5, or 65 mg/kg/day) by oral gavage for 3 months. Bone mineral density (BMD) was detected by micro-CT detection of left proximal medial metaphyseal tibia. Hematoxylin and eosin (H&E) and toluidine blue O staining were also performed. Serum levels of E2, ALP and testosterone were examined. Bone marrow-derived bone marrow stem cells (BMSCs) were isolated and treated with echinops-containing serum. Estrogen receptors (ER) including ERalpha and ERbeta in bone specimens and BMSCs were detected by qRT-PCR. Cell viability and colon formation of BMSCs were detected. Expressions of ERalpha, ERbeta, AKT, p-AKT, ERK, and p-ERK in BMSCs were detected by western blot. Results showed that echinops significantly increased trabecular interconnectivity, thickness of trabeculae, and connection of trabecula. Echinops significantly increased BMD and E2, but significantly reduced ALP and testosterone in dose-dependent manners. Echinops induced ERalpha and ERbeta in both bone specimens and BMSCs. Echinops enhanced cell viability and ability of colony formation of BMSCs, and increased ERalpha, ERbeta, p-AKT, and p-ERK. Thus, Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERalpha, ERbeta, p-AKT, and P-ERK in BMSCs. These results provide experimental basis for clinical prevention and treatment of postmenopausal osteoporosis by echniops. PMID- 29794405 TI - Cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-Met/ERK signaling pathway. AB - Cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad Bufo bufo gargarizans Cantor, is a well known traditional Chinese medicine widely used in clinical cancer therapy in China. Its therapeutic effect is especially pronounced in liver cancer. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. Here, we investigated the effects and mechanisms of cinobufacini on inhibiting HepG2 cells invasion and metastasis. Epithelial-mesenchymal transition (EMT) is identified as an important initiation step for HCC metastasis. After the HepG2 cells were treated with different concentrations of cinobufacini, the expression of EMT related E-cadherin was increased while N-cadherin and Vimentin were decreased, and the expression of EMT related transcription factors Snail and Twist were decreased. Moreover, the phosphorylation of c-Met was inhibited by cinobufacini, and the expression of MEK1/2 and ERK1/2, the downstream kinase of the signal transduction pathway activated by c-Met, also decreased in a dose dependent manner with cinobufacini. In addition, after the cells were treated with different concentrations of cinobufacini, there was a significant decrease in MMP-2 and MMP-9 expression in HepG2 cells. In conclusion, the current study suggested cinobufacini could prevent HepG2 cells migration and invasion via inhibiting EMT through c-Met/ERK signaling pathway, which might provide experimental evidence for cinobufacini treatment of HCC. PMID- 29794406 TI - Inter-individual Comparison of Gadobutrol and Gadoteridol Tissue Time-intensity Profiles for Dynamic Susceptibility Contrast Perfusion MR Imaging. AB - PURPOSE: Gadobutrol is a gadolinium-based contrast material (GBCM) with a high concentration of gadolinium and high relaxivity. Our purpose was to evaluate the signal intensity profiles in brain tissue for the bolus width and degree of signal change after bolus injection using an echo planar dynamic susceptibility contrast (DSC) sequence. We compared gadobutrol to gadoteridol using various injection speeds and saline flush volumes. METHODS: We studied 97 patients who underwent brain MRI. Datasets for perfusion studies were acquired using a 3T scanner with an echo planar imaging (EPI) sequence. The injection protocols were set up with combinations of injection speed and saline flush volume for both gadobutrol and gadoteridol. The full width at half maximum (FWHM) and the maximum signal change ratio (SCRmax) of the time intensity curves were measured. RESULTS: The FWHM did not show a statistically significant difference according to injection speed, flush volume, or type of GBCM. The SCRmax showed a greater change with a faster injection speed, larger saline flush, and gadobutrol administration. The difference between gadobutrol and gadoteridol became smaller with a faster injection speed and a larger saline flush. CONCLUSION: The maximum signal drop was larger with gadobutrol when the injection speed was slow and the saline flush was small. Thus, gadobutrol may be useful to obtain a better profile for DSC perfusion MRI in conditions requiring a slower injection speed and/or a smaller volume of saline flush. PMID- 29794407 TI - A Case of Uterine Tumor Resembling Ovarian Sex-cord Tumor (UTROSCT) Exhibiting Similar Imaging Characteristics to Those of Ovarian Sex-cord Tumor. PMID- 29794408 TI - Diffusion-weighting Caused by Spoiler Gradients in the Fast Imaging with Steady state Precession Sequence May Lead to Inaccurate T2 Measurements in MR Fingerprinting. AB - Magnetic resonance fingerprinting (MRF) is a promising framework that allows the quantification of multiple magnetic resonance parameters with a single scan. MRF using fast imaging with steady-state precession (MRF-FISP) has robustness to off resonance artifacts and has many applications in inhomogeneous fields. However, the spoiler gradient used in MRF-FISP is sensitive to diffusion motion, and may lead to quantification errors when the spoiler moment increases. In this study, we examined the effect of the diffusion weighting in MRF-FISP caused by spoiler gradients. The T2 relaxation times were greatly underestimated when large spoiler moments were used. The T2 underestimation was prominent for tissues with large values of T2 and diffusion coefficients. The T2 bias was almost independent of the apparent diffusion coefficient (ADC) and T2 values when the ADC map was measured and incorporated into the matching process. These results reveal that the T2 underestimation resulted from the diffusion weighting caused by the spoiler gradients. PMID- 29794409 TI - The Effects of Long-Term Dietary Therapy on Patients with Hypertriglyceridemia. AB - AIM: This study aimed to evaluate the effect of diet on serum lipids and to assess the effectiveness of long-term dietary therapy for hypertriglyceridemia. METHODS: Seventy-nine patients (34 males and 45 females) with hypertriglyceridemia were enrolled and underwent dietary counseling for 12 months based on the following three recommendations: (1) reduce carbohydrate intake, (2) increase n-3 polyunsaturated fatty acid (PUFA) intake, and (3) limit alcohol drinking. We examined the effect of dietary therapy for 6 months on serum triglyceride (TG) levels and also compared the effectiveness of dietary and combined drug therapies on preventing arteriosclerotic disease from 7 to 12 months. RESULTS: We observed that serum TG levels of the patients receiving dietary counseling were decreased compared with baseline at 6 months. Body weight and serum TG levels were decreased, and serum high-density lipoprotein levels were increased in the dietary therapy alone group, whereas BW, body mass index, and abdominal circumference were decreased in the combined drug treatment group compared with baselines at 6 and 12 months. Furthermore, the dietary therapy alone group demonstrated reductions in intake of total energy, carbohydrate, and saturated fatty acids, as well as n-6/n-3 PUFA ratio compared with baselines, but only n-6/n-3 PUFA ratio was decreased in the combined drug treatment group. CONCLUSION: This study demonstrated a decrease in serum TG level after 12 months of dietary therapy similar to drug therapy, which suggests that it is an effective treatment for hypertriglyceridemia, and heightened awareness should be made to encourage its use.The clinical trial registration number: UMIN000028860. PMID- 29794411 TI - Association of N-Terminal Pro B-Type Natriuretic Peptide With Blood Pressure and Pulse Pressure in Elderly People - A Cross-Sectional Population Study. AB - BACKGROUND: N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.Methods and Results:The present cross-sectional study involved 6,529 participants, aged >=70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those >=125 pg/mL. Subjects were divided into five groups based on PP (<50, >=50 to <60, >=60 to <70, >=70 to <80, and >=80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT proBNP. The odds ratios for high NT-proBNP concentrations in the PP >=80 and >=70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia. CONCLUSIONS: The results suggest that NT proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD. PMID- 29794410 TI - Relationship between CCL22 Expression by Vascular Smooth Muscle Cells and Macrophage Histamine Receptors in Atherosclerosis. AB - AIM: CCL22, mainly synthesized by monocyte-derived alternative (M2) macrophages, belongs to the CC family of chemokines and is involved in monocyte migration and recruitment. We have previously investigated CCL22 and histamine in atherosclerosis. Here, we investigated the hypothesis that CCL22 is involved in atherosclerosis, which is influenced by the differentiation of macrophage phenotypes via histamine. METHODS: CCL22 expression was investigated in human carotid arteries and coronary arteries with bare metal stents. Ligated carotid arteries of wild-type (C57BL/6J) and apolipoprotein E-deficient mice were also used as atherosclerotic models. The localization and expression of CCL22 and classical (M1)-like and M2-like macrophages in various human and mouse atherosclerotic lesions were investigated by immunohistochemical examination and quantitative real-time polymerase chain reaction. Histamine is expressed in atherosclerosis, and it induces inflammation and immunity. Human- and mice derived monocytes and macrophages were used to examine the role of histamine in macrophage differentiation and CCL22-expression. Macrophages derived from histamine receptor 1 (H1R)- and 2 (H2R)-knockout (KO) mice were also examined. RESULTS: Atherosclerotic lesions showed a distribution of heterogeneous macrophage phenotypes with M1-like and M2-like macrophage dominant sites. CCL22 was distributed in sparse areas of vascular smooth muscle cells (VSMCs) and associated with M2-like macrophages. Moreover, H2R stimulation was associated with CCL22 expression via M2-like macrophage dominant differentiation. CONCLUSION: The expression of M1- or M2-like macrophages in atherosclerosis were observed to be dependent on the distribution of VSMCs owing to differences in causal stimuli and the switching of histamine receptors via Th1 or Th2 cytokines. These results suggest that CCL22 may control atherosclerosis. PMID- 29794412 TI - Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins. AB - AIM: The Friedewald equation is the standard method for estimating low-density lipoprotein cholesterol (LDL-C) levels [LDL-C(F)] and fixes the ratio of triglyceride (TG) to very LDL-C at 5. However, this has been reported to underestimate LDL-C, particularly in patients with LDL-C <70 mg/dL. A novel method for LDL-C estimation [LDL-C(M)] using an adjustable factor instead of a fixed value of 5 has recently been proposed. The purpose of this study was to validate LDL-C(M) in Japanese patients with cardiovascular disease (CVD) treated with statins. METHODS: In 385 consecutive CVD patients treated with statins, LDL C(M) and LDL-C(F) levels were compared with directly measured LDL-C [LDL-C(D)]. RESULTS: Mean LDL-C(D), LDL-C(F), and LDL-C(M) were 81.7+/-25.5, 76.4+/-24.6, and 79.9+/-24.5 mg/dL, respectively. In all patients, both LDL-C(F) and LDL-C(M) were significantly correlated with LDL-C(D) [LDL-C(F) vs. LDL-C(D): R=0.974, p<0.001; LDL-C(M) vs. LDL-C(D): R=0.987, p<0.001]. In patients with LDL-C(D) <70 mg/dL, LDL-C(M) showed a better correlation with LDLC(D) compared with LDL-C(F) [LDL C(M) vs. LDL-C(D): R=0.935, p<0.001; LDL-C(F) vs. LDLC(D): R=0.868, p<0.001]. In contrast, the correlation of LDL-C(D) with LDL-C(M) or LDL-C(F) was similar in patients with LDL-C(D) >=70 mg/dL. CONCLUSIONS: In Japanese patients with CVD treated with statins, LDL-C level estimated by this novel method might be more accurate than those estimated using the Friedewald equation for LDL-C levels <70 mg/dL. PMID- 29794414 TI - Fulminant type 1 diabetes mellitus in Japanese children and adolescents: multi institutional joint research of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. AB - Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics. PMID- 29794413 TI - Co-occurrence Network Reveals the Higher Fragmentation of the Bacterial Community in Kaidu River Than Its Tributaries in Northwestern China. AB - Rivers and their tributaries sculpt the earth's surface, and play an important role in substance circulation and energy flow. Bacteria are involved in most biogeochemical processes in the fluvial ecosystem; however, their pattern distribution in a river and its tributaries has not yet been investigated in detail. In the present study, high-throughput sequencing was employed to examine bacterial communities and their co-occurrence networks between Kaidu River and its nine tributaries in northwestern China. The results obtained demonstrated that both bacterial communities shared a similar dominant sub-community, mainly consisting of Actinobacteria, Bacteroidetes, and Proteobacteria, with Limnohabitans and Variovorax as the dominant genera. In spite of these commonalities, bacterial community structures still significantly differed between these two habitats, which may be related to the distance-related dispersal limitation. Their co-occurrence networks were generally both positively structured. The structural analysis showed that OTUs from the same phyla were more likely to co-occur. Although the keystone genera were taxonomically different between Kaidu River and its tributaries, they both shared common trophic properties in exploiting niches under oligotrophic conditions. We noted that their relative abundances were less than 1%, indicating the over proportional roles of rare genera in the bacterial community. In addition, the inferred networks showed less nodes and edges, but higher modularity in Kaidu River than its tributaries, suggesting the higher fragmentation of the bacterial community in the mainstream. PMID- 29794415 TI - Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System. AB - The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. PMID- 29794417 TI - Extended Applications for Cochlear Implantation. AB - The indications for cochlear implantation (CI) have expanded over the last few years. There is evidence that some adult patients with pre- or perilingual onset of deafness may gain from implantation. Similarly, CI in patients with single sided deafness may offer significant benefits in terms of quality of life and social as well as academic development. In this setting, directional hearing may be restored and speech comprehension, especially in noise, may be optimized. In patients with intractable tinnitus and profound hearing loss, CI not only improves speech perception, but also helps to reduce the tinnitus in the deaf ear. PMID- 29794416 TI - SKLB060 Reversibly Binds to Colchicine Site of Tubulin and Possesses Efficacy in Multidrug-Resistant Cell Lines. AB - BACKGROUND/AIMS: Many tubulin inhibitors are in clinical use as anti-cancer drugs. In our previous study, a novel series of 4-substituted coumarins derivatives were identified as novel tubulin inhibitors. Here, we report the anti cancer activity and underlying mechanism of one of the 4-substituted coumarins derivatives (SKLB060). METHODS: The anti-cancer activity of SKLB060 was tested on 13 different cancer cell lines and four xenograft cancer models. Immunofluorescence staining, cell cycle analysis, and tubulin polymerization assay were employed to study the inhibition of tubulin. N, N ' Ethylenebis(iodoacetamide) assay was used to measure binding to the colchicine site. Wound-healing migration and tube formation assays were performed on human umbilical vascular endothelial cells to study anti-vascular activity (the ability to inhibit blood vessel growth). Mitotic block reversibility and structural biology assays were used to investigate the SKLB060-tubulin bound model. RESULTS: SKLB060 inhibited tubulin polymerization and subsequently induced G2/M cell cycle arrest and apoptosis in cancer cells. SKLB060 bound to the colchicine site of beta-tubulin and showed antivascular activity in vitro. Moreover, SKLB060 induced reversible cell cycle arrest and reversible inhibition of tubulin polymerization. A mitotic block reversibility assay showed that the effects of SKLB060 have greater reversibility than those of colcemid (a reversible tubulin inhibitor), indicating that SKLB060 binds to tubulin in a totally reversible manner. The crystal structures of SKLB060-tubulin complexes confirmed that SKLB060 binds to the colchicine site, and the natural coumarin ring in SKLB060 enables reversible binding. CONCLUSIONS: These results reveal that SKLB060 is a powerful and reversible microtubule inhibitor that binds to the colchicine site and is effective in multidrug-resistant cell lines. PMID- 29794419 TI - Stepwise Excavation. AB - The most recent inspiration for stepwise carious tissue removal in 2 stages originates from the knowhow on intralesion changes in deep carious lesions. The environmental change that takes place during the first stage of carious tissue removal is aiming for the arrest of the deep lesion, by placing a temporary restoration on top of the soft carious dentine. The cavity is optimised during the second stage for a final restoration, as potential shrinkage of the retained dentine may occur during the period of carious dentine arrestment. However, basic clinical limitations on the objective evaluation of pulp inflammation creates dilemmas in treating the deep lesions. Also, a global consensus is lacking for the definition of a so-called deep lesion. Finally, an optimal evidence goal for choosing the best approach for deep lesion treatment in adults has still not been fully defined. Taken together, it may not be a surprise that treatment variation is reported amongst general dental practitioners on deep caries treatment. Here, facts are presented supporting the treatment, including some drawbacks, as well as updated guidelines for the procedure. Recent clinical high evidence data from randomised clinical trials significantly favour the stepwise approach as a predictable and reliable treatment for well-defined deep carious lesions located in the pulpal quarter of the dentine in terms of avoiding pulp exposure, keeping the tooth vital and without the development of apical pathosis. PMID- 29794418 TI - Proteomics Analysis of Testis of Rats Fed a High-Fat Diet. AB - BACKGROUND/AIMS: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. METHODS: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. RESULTS: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. CONCLUSION: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non coding RNAs may provide new candidates to explore the mechanisms of obesity induced male infertility for both protein and epigenetic pathways. PMID- 29794420 TI - Removing or Controlling? How Caries Management Impacts on the Lifetime of Teeth. AB - Historically, traditional carious lesion management focused on the importance of removal of all carious tissue, with little thought to the lesion origins. The surgical removal of any sign of a carious lesion was prioritised with little, or no, consideration to pulp vitality, loss of tooth structure, or caries disease management. This symptomatic approach concentrating on lesions rather than on the cause of the disease, focused on preventing secondary carious lesion development. Early detection and improved understanding of the caries process - that lesion progress can be arrested or slowed - has led to preventive measures and less destructive management as a focus. The choice of lesion management depends on: whether a primary or permanent tooth is involved; which tooth surface(s) is/are involved; whether the lesion is confined to enamel or extends into dentine; the lesion depth, and lesion cleansability. Use of preventive and minimally invasive operative strategies is complicated by the lack of predictable ways of recording lesions' status to allow early detection of failed strategies and early intervention. Because re-restoration usually makes the cavity larger and, consequently, the tooth weaker, the clinician should be certain about initiating the repeat restoration cycle, delaying the first restoration as much as possible. The 3 main principles that support preventing or slowing the repeat restoration cycle are: (1) avoid restoration placement until there is no other option; (2) place them for maximum longevity; (3) if re-restoration is necessary, repair or refurbishment is preferable to replacement of a defective restoration. PMID- 29794422 TI - Advances in the Field of Bone Conduction Hearing Implants. AB - The number of marketed bone-conduction hearing implants (BCHIs) has been steadily growing, with multiple percutaneous devices and transcutaneous devices now available. However, studies assessing efficacy often have small sample sizes and employ different assessment methodologies. Thus, there is a paucity of evidence to guide clinicians to the most appropriate device for each patient. This paper outlines audiological guidelines for the latest devices, as well as research from the most up-to-date clinical trials. We also outline the evidence base for some potentially contentious issues in the field of bone conduction, including bilateral fitting of BCHIs in those with bilateral conductive hearing loss as well as the use of BCHIs in single-sided deafness (SSD). Bilateral fitting of BCHIs have been found to significantly increase the hearing thresholds in quiet and improve sound localization, but to give limited benefits in background noise. Studies conducted via multiple assessment questionnaires have found strong evidence of subjective benefits for the use of BCHIs in SSD. However, there is little objective evidence of benefit for SSD patients from sound localization and speech in noise tests. PMID- 29794421 TI - Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells. AB - BACKGROUND/AIMS: Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. METHODS: HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. RESULTS: We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. CONCLUSIONS: Our results suggest the potential use of cobimetinib in colorectal cancer therapy. PMID- 29794423 TI - Pathophysiology of Dental Caries. AB - Carious lesion dynamics are dependent predominantly on the availability of fermentable sugars, other environmental conditions, bacteria, and host factors. Our current understanding of the microorganisms involved in the initiation and progression of caries is still rather incomplete. The most relevant acidogenic aciduric bacterial species known to date are Streptococcus mutans, bifidobacteria, and lactobacilli. Whereas mutans streptococci are initiators, bifidobacteria and lactobacilli are more enhancers for progression. Boosters for microbial activity are specific environmental conditions, such as the presence of fermentable dietary sugars and the absence of oxygen. Based on these conditions, the necrotic and/or contaminated zone fulfils all criteria for disease progression and has to be removed. For those deep lesions where the pulp vitality is not affected, a selective removal of the contaminated leathery dentine should take place as this approach lowers the risk of regrowth of the few embedded microbial cells here. In repelling the microbial attack and repairing damage, the host has developed several ingenious strategies. A major resistance to carious lesion progression is mounted by the dentine-pulp tissues. The signalling molecules and growth factors released upon dentine demineralisation upregulate the odontoblast activity and act as sensor cells. After carious stimulation, odontoblasts initiate an inflammatory reaction by producing chemokines and synthesise a protective tertiary dentine. After the destruction of these cells, the pulp still has a high capacity to synthesise this tertiary dentine thanks to the presence of adult stem cells within the pulp. Also, in addition to the systemic regulation, the pulp which is located within inextensible the confines of the dentine walls has a well-developed local regulation of its inflammation, regeneration, and vascularisation. This local regulation is due to the activity of different pulp cell types, mainly the fibroblasts, which secrete soluble molecules that regulate all these processes. PMID- 29794426 TI - Hearing Rehabilitation in Congenital Middle Ear Malformation. AB - Microtia and atresia cause significant conductive hearing loss of up to 60 dB HL. The bilateral cases suffer from severely restricted communication abilities and require immediate acoustic stimulation. There is also growing evidence that unilateral cases benefit from an early and selective stimulation of the affected side. Hearing restoration can be performed in selected cases of minor malformation by classic middle ear reconstruction. However, the majority of patients presumably benefit better from a hearing aid. There are 3 main types: active middle ear implants, active bone conduction implants and passive bone conduction implants. All implants improve speech perception, speech recognition, the signal-to-noise ratio and directional hearing. The extent varies among implants and requires further studies. Decision making on the implant type depends on the extent of malformation and hence the preoperative imaging. New scoring systems provide reliable risk stratification. Second it depends on the age of the patient. The active middle ear implants provide a selective stimulation of the affected side and are beneficial if implanted in the first years of life during the maturation period of the auditory system. In conclusion, hearing rehabilitation of congenital atresia should be performed as early as possible. This includes not only the bilateral but also the unilateral affected patients. PMID- 29794427 TI - Brain Plasticity and Rehabilitation with a Cochlear Implant. AB - The functional changes that occur in the brain due to deafness may affect the way the auditory system processes sound after cochlear implantation. Brain plasticity plays a crucial role in the success of cochlear implantation to facilitate or develop spoken language in profoundly deaf individuals. The functional plasticity that occurs in postlingually deaf adults during periods of deafness can both support and hinder speech understanding with a cochlear implant, depending on the nature and degree of functional changes. Evidence so far suggests that the strategies people use to communicate while deaf may influence whether the functional changes are adaptive or maladaptive. In the case of children with congenital deafness, evidence is very strong for a sensitive period in which auditory input must be restored if subsequent oral language is to be developed successfully. Successful oral language use and speech understanding in individuals implanted after 7 years of age depends strongly on the pre-implant use of hearing aids and auditory-verbal communication. Future research should focus on how to harness our growing knowledge of brain plasticity to optimize the outcomes of cochlear implantation in each individual. PMID- 29794428 TI - Gremlin2 Regulates the Differentiation and Function of Cardiac Progenitor Cells via the Notch Signaling Pathway. AB - BACKGROUND/AIMS: The transplantation of cardiac progenitor cells (CPCs) improves neovascularization and left ventricular function after myocardial infarction (MI). The bone morphogenetic protein antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. The present study examined the role of Grem2 in CPC differentiation and cardiac repair. METHODS: To determine the role of Grem 2 during CPC differentiation, c-Kit+ CPCs were cultured in differentiation medium for different times, and Grem2, Notch1 and Jagged1 expression was determined by RT-PCR and western blotting. Short hairpin RNA was used to silence Grem2 expression, and the expression of cardiomyocyte surface markers was assessed by RT-PCR and immunofluorescence staining. In vivo experiments were performed in a mouse model of left anterior descending coronary artery ligation-induced MI. RESULTS: CPC differentiation upregulated Grem2 expression and activated the Notch1 pathway. Grem2 knockdown inhibited cardiomyocyte differentiation, and this effect was similar to that of Notch1 pathway inhibition in vitro. Jagged1 overexpression rescued the effects of Grem2 silencing. In vivo, Grem2 silencing abolished the protective effects of CPC injection on cardiac fibrosis and function. CONCLUSIONS: Grem2 regulates CPC cardiac differentiation by modulating Notch1 signaling. Grem2 enhances the protective effect of CPCs on heart function in a mouse model of MI, suggesting its potential as the rapeutic protein for cardiac repair. PMID- 29794429 TI - Serum Fas Ligand, Serum Myostatin and Urine TGF-beta1 Are Elevated in Autosomal Dominant Polycystic Kidney Disease Patients with Impaired and Preserved Renal Function. AB - BACKGROUND/AIMS: The pathophysiology of renal disease progression in autosomal dominant polycystic disease (ADPKD) is largely unknown. Recent evidence suggests microvascular dysfunction leading to renal ischemia, as an additional pathway for renal function decline. This study examined the levels of serum Fas ligand (FasL), serum myostatin and urine transforming growth factor-beta 1 (TGF-beta1) and their association with markers of endothelial dysfunction, in ADPKD patients with preserved or impaired renal function. METHODS: Seventy-eight participants were enrolled in the study, divided in three groups: Group A consisted of 26 ADPKD patients with impaired renal function (eGFR 45-70 ml/min/1.73m2), Group B of 26 ADPKD patients with preserved renal function (eGFR > 70 ml/min/1.73m2), and Group C of 26 age- and sex- matched controls with no history of renal disease. Serum FasL, myostatin and urine levels of TGF-beta1 were measured as biomarkers of vascular dysfunction, apoptosis and fibrosis with ELISA techniques. RESULTS: Group A patients had significantly higher levels of FasL (13.12+/-1.69 ng/mL), myostatin (4.62+/-0.59 ng/mL) and urine logTGF-beta1 (3.56+/-0.49 ng/24h) compared to Group B (9.6+/-1.28 ng/mL, 3.06+/-0.35, and 2.09+/-0.37, respectively, p< 0.001 for all comparisons) or controls (6.59+/-1.17 ng/mL, 2.18+/-0.45 ng/ml, and 1.58+/-0.21, respectively, p< 0.001 for all comparisons). Patients in Group B had also higher levels of all markers compared to controls (p< 0.001), despite having similar renal function. In ADKPD patients negative associations of eGFR with FasL (r=-0.799, p< 0.001), myostatin (r=-0.856, p< 0.001) and TGF-beta1 (r=-0.476, p< 0.001) but positive correlations of these markers with asymmetric dimethylarginine (ADMA) (r=0.825; r=0.749; and r=0.599, respectively p< 0.001) were noted. Multivariate analysis demonstrated that FasL was independently associated with high urine TGF-beta1 (OR 3.774, 95%CI 1.180 12.072, p=0.025). CONCLUSIONS: ADPKD patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-beta1 than controls. These results indicate that an interplay between endothelial dysfunction and renal ischemia with mechanisms linked to apoptosis and fibrosis may be present even in early stages of ADPKD. PMID- 29794430 TI - Diagnosis of Vertigo and Dizziness Syndromes in a Neurological Outpatient Clinic. AB - BACKGROUND: Dizziness and vertigo are frequent complaints of outpatients in the neurological department. Our objective was to explore the epidemiological category and clinical features of patients with dizziness or vertigo in the neurological outpatient department of a tertiary hospital. METHODS: We consecutively recruited all patients with dizziness and/or vertigo visiting the neurological outpatient clinic of the First Affiliated Hospital of Chongqing Medical University from January 2016 to June 2017. All patients were interviewed by 4 neurologists and they completed self-administered questionnaires. General physical and standardized neuro-otology bedside examinations were performed in all participants. Instrumental examinations and other related examinations were prescribed as needed. RESULTS: A total of 392 patients, 272 female and 120 male, were enrolled and the ratio of males to females was 1: 2.27. The mean age was 52.39 +/- 13.87 years (range 11-90). Elderly patients (>=60 years) accounted for about one-third of the patients. Peripheral vestibular disorders accounted for 54.6% of patients, central vestibular disorders (including vestibular migraine [VM]) accounted for 22.4% of patients, psychogenic vertigo in 64 (16.3%), other reasons in 9 (2.3%) and unknown in 17 (4.3%). Benign paroxysmal positional vertigo (BPPV; 30.8%), psychiatric dizziness (20.5%), and VM (14.4%) were the 3 major vestibular diseases in patients under 60 years of age; however, BPPV (27.9%), central vertigo (21.7%), and Meniere's disease (11.7%) were more common in patients over 60 years of age. CONCLUSIONS: This study provided a classification and clinical features of vestibular disorders in a neurological outpatient department of a tertiary hospital in China. The spectrum of vertigo or dizziness is different between different age groups and clinicians should pay attention to this difference in clinical reasoning. PMID- 29794431 TI - The Problem: Relevance, Quality, and Homogeneity of Trial Designs, Outcomes, and Reporting. AB - Clinical trials are the cornerstone of evidence-based medicine. By directly comparing different interventions they produce evidence on their relative efficacy and effectiveness This, in turn, can inform secondary research and guideline development to facilitate evidence-based clinical decision making. However, the quality of evidence stemming from clinical trials is frequently poor. Here, the pathway of evidence from basic research to the generation of implementable clinical guidelines will be described. Relevant factors related to trial design and reporting, such as the choice of trial comparators, outcomes and outcome measures, will be described and their influence on evidence synthesis will be discussed. Finally, recommendations on how to improve trials in order to increase their usefulness for evidence generation will be given. PMID- 29794434 TI - Hearing Rehabilitation with Active Middle Ear Implants. AB - Hearing implant technology is evolving at a rapid rate and more than ever patients with hearing loss are benefiting from these emerging hearing devices. Active middle ear implants are alternatives to hearing aids and bone conducting devices, offering patients an expanded range in improving their hearing. This chapter looks at the devices currently available, their indications and the literature regarding their outcomes. PMID- 29794433 TI - Optimizing Ossicular Prosthesis Design and Placement. AB - Middle ear hearing reconstruction is unpredictable. Difficulties arise because of host factors, such as ventilation or scarring, surgical technique factors, such as prosthesis placement and stabilization, and design and mechanical factors influencing the properties of the prosthesis. Often there is a balancing act between choosing optimal stability, and maximizing the mechanical vibrations of the prosthesis. We review our and other investigators' work, in design and ideal placement of middle ear prostheses. Middle ear prostheses need to be rigid enough to deliver acoustic forces without bending. Prosthesis mass has a modest effect at higher frequencies. A key point is that rotational movements of the prosthesis have to be constrained. Prosthesis head size and cartilage interposition, within reason, have little effect on vibration transmission. Reconstruction to the malleus may have some small mechanical advantage; however this is not clearly proven. Similarly, there is no proven advantage in reconstructing to the stapes head instead of the footplate. The most important factor for good long term results is probably the stability of the prosthesis, both to acute inertial forces such as trauma, and to slower term changes such as tympanic membrane position and scarring contractures. PMID- 29794435 TI - Restoring the Carious Lesion. AB - Restoring carious lesions can be challenging, especially for deep lesions in proximity to the pulp. A number of factors can influence restoration longevity. This chapter will discuss aspects that should be considered when restoring carious lesions. In the first part, factors that might have an effect on the pulp such as preparation trauma, tooth hypersensitivity, and the use of liners will be described. In the second part, the challenges and limitations of adhesive bonding to (sound and carious) dentine will be discussed. Lastly, recommendations on the suitability of different bonding techniques and restorative materials in different situations will be given. PMID- 29794432 TI - Endogenous Hydrogen Sulfide Ameliorates NOX4 Induced Oxidative Stress in LPS Stimulated Macrophages and Mice. AB - BACKGROUND/AIMS: Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure. Cystathionine-gamma-lyase (CSE)/ hydrogen sulfide (H2S) has potential anti inflammatory activities in a variety of inflammatory diseases. NADPH oxidase 4 (Nox4), a member of the NADPH oxidases, is the major source of reactive oxygen species (ROS) and its expression is increased in sepsis, but its function in CSE mediated anti-inflammatory activities remains unknown. METHODS: Macrophages were either transfected with CSE, Nox4 siRNA or transduced with lentiviral vector encoding CSE or Nox4, and then stimulated with lipopolysaccharide (LPS). The expression of inflammatory mediators and signaling pathway activation were measured by quantitative PCR (qPCR), ELISA, and immunoblotting. LPS-induced shock severity in WT, Nox4 knockdown and CSE knockout (CSE-/-) mice was assessed. RESULTS: Here we showed that CSE and Nox4 were upregulated in macrophage and mouse in response to LPS. After LPS stimulation, the inflammatory responses were significantly ameliorated by lentiviral Nox4 shRNA knockdown, but were exacerbated by lentiviral overexpressing Nox4. Furthermore, Nox4 mediated inflammation through PI3K/Akt and p-p38 mitogen-activated protein kinase signal pathway. Notably, CSE knockout served to amplify the inflammatory cascade by increasing Nox4-ROS signaling activation in septic mice and macrophage. Similarly, the enhanced production of inflammatory mediators by macrophages was reduced by CSE overexpression. CONCLUSION: Thus, we demonstrated that CSE/H2S attenuated LPS-induced sepsis against oxidative stress and inflammation damage probably largely through mediated Nox4 pathway. PMID- 29794437 TI - MicroRNA-223 Suppresses Osteoblast Differentiation by Inhibiting DHRS3. AB - BACKGROUND/AIMS: In this study, we aimed to use bioinformatics tools to identify the specific miRNAs and mRNAs involved in osteogenic differentiation and to further explore the way in which miRNA regulates osteogenic differentiation. METHODS: The microarray GSE80614, which includes data from 3 human mesenchymal stromal cells (hMSCs) and 3 hMSCs after 72 hours (hr) of osteogenic differentiation, was used to screen for differentially expressed mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of these mRNAs were conducted using Gene Set Enrichment Analysis (GSEA). Then, the miRanda website was employed to detect the binding sites of DHRS3. In vitro experiments, including RT-PCR and western blotting, were used to detect miR-233 and DHRS3 expression levels 7 and 14 days (d) after the induction of osteogenic differentiation using human bone marrow-derived mesenchymal stem cells (hBMSCs). The target relationship between miR-223 and DHRS3 was confirmed by a dual luciferase assay. ALP (alkaline phosphatase) staining, ARS (Alizarin Red S) staining and western blotting (Runx2, OPN, OCN) were used to detect the level of osteogenic differentiation after transfection with miR-223 mimics and DHRS3 cDNA. RESULTS: In this study, 127 mRNAs differentially expressed during osteogenic differentiation were identified in GSE80614. GO term and KEGG pathway enrichment analyses found that the retinol metabolism pathway was activated during osteogenic differentiation and that DHRS3, which is involved in the pathway, was upregulated. During osteogenic differentiation in hBMSCs, miR-223 was gradually downregulated, while DHRS3 was upregulated. After 14 days of osteogenic differentiation, ALP and ARS staining assay results showed strong ALP activity and extracellular matrix calcification with the inhibition of miR-223 or the overexpression of DHRS3. Furthermore, the expression levels of Runx2, OPN, and OCN were upregulated with the knockdown of miR-223 or the overexpression of DHRS3, while the simultaneous transfection of a miR-223 agomir and DHRS3 cDNA resulted in no significant difference from the negative control (NC) group. CONCLUSION: The inhibition of miR-223 promotes the osteogenic differentiation of hBMSCs via the upregulation of DHRS3. PMID- 29794436 TI - By Activating Akt/eNOS Bilobalide B Inhibits Autophagy and Promotes Angiogenesis Following Focal Cerebral Ischemia Reperfusion. AB - BACKGROUND/AIMS: Ischemic stroke is a leading cause of long-term disability. To date, there is no effective treatment for stroke. Previous studies have shown that Ginkgo biloba extract has protective effects against neurodegenerative disorders. In this present study, we sought to test the potential protective role of an active component of Ginkgo biloba extract, bilobalide, in a rat model of middle cerebral artery occlusion (MCAO). METHODS: A rat model of MCAO was used to test the potential protective effects of Bilobalide B on stroke protection. TTC staining was performed to evaluate infarct size of the brains. Neurological deficit score was measured to reveal the effects of the treatments on animal behavior and cognition. Immunohistochemical staining and transmission electronic microscope analysis were performed to measure the cellular responses to drug treatment. Western blotting and ELISA were performed. The expression of Cleaved- Casepase 3, Beclin-1, p62 and LC3I/II were quantified, and the Phosphorylation of eNOS and Akt were evaluated. The ratio of Bcl-2/ Bax was determined to reveal the molecular pathways that are involved in the drug treatment. RESULTS: We found that intraperitoneal delivery of various Bilobalide doses during ischemia can protect against brain injury, as evidenced by reduced infarct size and improved neurological scores after surgery. Histochemical analysis revealed that treatment with bilobalide can significantly reduce apoptosis, autophagy, and promote angiogeneis following ischemia/reperfusion injury to the brain. The performence of increased phosphorylation of eNOS and Akt suggested that bilobalide can activate Akt prosurvival and eNOS pathways to promote cell survival and angiogenesis, respectively. CONCLUSIONS: Our results suggested that bilobalide benefits stroke symptoms by reducing cell death pathways and promoting angiogenesis. As such, bilobalide may be a potential agent for improving self repair after ischemic stroke. PMID- 29794438 TI - Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis. AB - BACKGROUND/AIMS: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. MATERIALS AND METHODS: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c kit protein expression and SCF and c-kit mRNA levels, respectively. RESULTS: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). CONCLUSIONS: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder. PMID- 29794439 TI - Clinical Recommendations on Carious Tissue Removal in Cavitated Lesions. AB - Non-cleansable carious lesions where sealing is no longer an option should be restored in the vast majority of cases. Prior to restoring the cavity, carious tissue removal is performed, mainly to increase the longevity of the restoration. Such removal, however, should not be conducted in a way that the vital pulp is harmed. This means that in teeth with shallow or moderately deep lesions, selective removal to firm dentine is recommended, while in deep lesions (radiographically extending into the pulpal third or quarter of the dentine) selective removal to soft dentine should be performed. In permanent teeth, stepwise removal is a possible alternative, while in primary teeth the Hall Technique can be considered too. To assess carious tissue removal, the hardness of the dentine should be the primary criterion. Moisture, colour, and additional parameters (like fluorescence of bacterial porphyrins, etc.) might be used, but should be critically evaluated towards their validity and patients' benefit. There is insufficient evidence to recommend a specific single carious tissue removal method. However, hand or chemomechanical excavation seem useful, as they reduce pain and discomfort during treatment. Current evidence also does not support any specific restoration material or (bonding) strategy for restoring cavities resulting from different carious tissue removal strategies. Prior to restoring the cavity, cavity disinfection is not recommended any longer. PMID- 29794442 TI - Sealing Carious Tissue Using Resin and Glass-Ionomer Cements. AB - One of the most conservative ways to retain tooth structure, preserve pulpal health, and avoid invasive treatment is to simply completely seal established carious lesions. A tight seal to isolate the biofilm and arrest the lesion can be successfully achieved using a sealant material such as resin or glass-ionomer for non-cavitated lesions, a restorative material for cavitated lesions, or, for primary teeth, preformed stainless-steel crowns. This chapter focuses on sealants and restorative materials. Sealant materials are a viable treatment option for controlling non-cavitated lesions in occlusal and proximal surfaces where there is no significant breach in the surface integrity of the tooth, even if the lesion extends into dentine. Resin infiltration can also be used to manage proximal non-cavitated lesions. Even when the exact depth of lesion that can be sealed has not been established, evidence supports sealing shallow and moderate deep lesions into dentine. For cavitated lesions, sealing lesions without carious tissue removal might be an option when removal of tooth tissue is not required to provide a hard periphery around the lesion/cavity margin (to enhance bonding or to increase cavity depth for enough restorative material to be placed to last). There is little evidence for placing a restorative material over cavitated carious lesions without tissue removal or preparation. However, where there is a significant breach in the surface integrity of the tooth but there is still enough sound tooth tissue to provide bonding for an adhesive restoration, sealing in carious tissue might still be an option. PMID- 29794440 TI - Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting TLR4-Mediated Autophagic Activation via the TRAF6-Beclin1-PI3KC3 Pathway. AB - BACKGROUND/AIMS: Lipopolysaccharide (LPS) plays a critical role in excessive inflammatory cytokine production during sepsis. Previously, artesunate (AS) was reported to protect septic mice by reducing LPS-induced pro-inflammatory cytokine release. In the present study, the possible mechanism of the anti-inflammatory effect of AS was further investigated. METHODS: An enzyme-linked immunosorbent assay was used to detect TNF-alpha and IL-6 release from macrophages. Specific small interfering RNAs (siRNAs) were used to knockdown the mRNA expression of target genes. Transmission electron microscopy and laser confocal microscopy were used to observe changes in autophagy. Western blotting was performed to detect the protein levels of tumor necrosis factor receptor-associated factor6 (TRAF6), Beclin1, phosphatidylinositol 3-kinase class III (PI3KC3), autophagy-related protein 5 (ATG5), and sequestosome 1. Immunoprecipitation (IP) and fluorescent co localization were used to detect the interactions between TRAF6-Beclin1 and Beclin1-PI3KC3, and the ubiquitination of Beclin1. RESULTS: AS inhibited TNF alpha and IL-6 release from RAW264.7 cells, mouse bone marrow-derived monocytes (BMDMs) and peritoneal macrophages (PMs) induced by LPS. However, the inhibition by AS of LPS-induced cytokine release decreased when autophagy was inhibited using 3-MA, bafilomycin A1, or a siRNA targeting the Atg5 gene. Notably, AS showed an inhibition of LPS-induced autophagic activation not degradation. Whereas, these effects of AS were lost in macrophages lacking TLR4 and decreased in macrophages with down-regulated TRAF6, indicating that AS inhibited LPS induced cytokine release and autophagic activation via TLR4-TRAF6 signaling. Western blotting results showed AS could reduce the levels of TRAF6, Beclin1, and PI3KC3. Importantly, the IP results showed AS only inhibited K63-linked ubiquitylation not total ubiquitylation of Beclin1 by acting on TRAF6. This interrupted the TRAF6-Beclin1 interaction and subsequent the formation of Beclin1 PI3KC3 core complex of the PI3K-III complex. CONCLUSION: AS inhibited LPS induced cytokine release from macrophages by inhibiting autophagic activation. This effect was tightly related to blockade of the TRAF6-Beclin1-PI3KC3 pathway via decreasing K63-linked ubiquitination of Beclin1 and then interrupting the formation of Beclin1-PI3KC3 core complex of the PI3K-III complex. Our findings reveal the mechanism of AS's anti-inflammatory effect and is significant for future targeted investigations of sepsis treatment. PMID- 29794443 TI - New Imaging Modalities in Otology. AB - Despite steady improvements in cross-sectional imaging of the ear, current technologies still have limitations in terms of resolution, diagnosis, functional assessment and safety. In this chapter, state-of-the-art imaging techniques in current clinical practice are presented including cone-beam computerized tomography, non-echo planar imaging magnetic resonance imaging, imaging for labyrinthine hydrops and imaging of the central auditory pathways. Potential future imaging modalities are also presented, including optical coherence tomography (OCT) and high-frequency ultrasound (HFUS) of the ear. These experimental modalities offer new opportunities for the assessment of ear structure and function. For example, middle ear structures can be visualized through the tympanic membrane, basilar membrane vibrations can be assessed through the round window and the passage of cochlear implants can be assessed in decalcified cochlear. Functional assessment of the middle ear using Doppler techniques are also discussed, including measurement of tympanic membrane and middle ear vibration amplitudes, visualization of dynamic changes, such as tensor tympani movements and movement of the tympanic membrane with breathing. These new modalities currently have limitations that preclude mainstream clinical use. For example, OCT is limited by the optical scattering of the thickened tympanic membrane and HFUS needs a coupling medium such as gel or fluid from the transducer to the imaged structure although it can visualize through thicker tissues. Nevertheless, further development of these novel techniques may provide an enhanced ability to assess the ear in conjunction with current technologies. PMID- 29794444 TI - Association of Five Snps in Cytotoxic T-Lymphocyte Antigen 4 and Cancer Susceptibility: Evidence from 67 Studies. AB - BACKGROUND/AIMS: CTLA-4 polymorphisms are associated with susceptibility to various cancers, but the results are often conflicting. Hence, we performed a comprehensive meta-analysis to quantitatively investigate the association between CTLA-4 polymorphisms (rs231775, rs4553808,rs5742909, rs3087243 or rs733618) and cancer risk. METHODS: Data were collected from PubMed and Web of Science. A total of 67 case-control studies were selected for quantitative analysis. Stata (Version 12) software was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to evaluate the strength of the associations. Subgroup meta-analysis was conducted based on ethnicity and cancer type. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. RESULTS: rs231775, rs4553808 and rs5742909 but not rs3087243 and rs733618 were significantly related to cancer risk. In analyses stratified by ethnicity, both rs231775 and rs4553808 were significant susceptibility polymorphisms in an Asian population but not in a Caucasian population. Moreover, there were stronger associations between the rs231775 polymorphism and increased risk of bone, breast, liver, head and neck and pancreatic cancers. Additionally, rs4553808 was associated with significantly increased susceptibility to breast cancer and head and neck cancer. CONCLUSION: rs231775, rs4553808 and rs5742909 may be used as predictive genetic biomarkers for cancer predisposition. Combined detection of CTLA-4 SNPs could be a useful tool for prediction of cancer susceptibility in clinical practice. PMID- 29794445 TI - Removing Carious Tissue: Why and How? AB - Caries is no longer seen as an infectious disease, and the aim of treating carious lesions is to control their activity, not to remove the lesion itself. Such control can be implemented by sealing off the lesion from the environment, with sealed bacteria being deprived from carbohydrates and thus inactivated. For cavitated lesions, controlling them usually involves the placement of restorations to rebuild the cleansability of the surface. In this case, dental practitioners have traditionally removed carious tissues prior to the restoration. This has historically been for a number of reasons, while today the main reason for restoring a cavity is to maximise restoration longevity. In shallow lesions, dental practitioners should aim to remove as much carious tissue as possible (to allow adequate depth for the restorative material) without unnecessarily removing sound or remineralisable dentine. This means removal to hard dentine around the periphery, to firm dentine centrally for optimising restoration longevity and allowing a tight cavity seal. For deep lesions in teeth with vital pulps (without irreversible pulpitis), maintaining pulp vitality is critical. Dental practitioners should aim to avoid pulp exposure, leaving soft or leathery dentine in pulpoproximal areas. Peripherally, hard tissue is left, again to ensure a tight seal and sufficient mechanical support of the restoration. As an alternative to the selective removal to soft dentine, stepwise removal can be used. With this approach, the soft dentine is temporarily rather than permanently sealed in, and removed in a second step after 6-12 months. Strategies where carious tissue in cavitated lesions is not removed at all, but sealed or managed non-restoratively, are currently restricted to primary teeth. PMID- 29794446 TI - Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality and Renal Outcomes in Patients with Diabetes and Albuminuria: a Systematic Review and Meta-Analysis. AB - BACKGROUND/AIMS: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. METHODS: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR>=30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). RESULTS: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. CONCLUSION: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria. PMID- 29794449 TI - Caries Epidemiology and Its Challenges. AB - Despite their limitations, caries epidemiology continues to rely predominantly on visual/tactile indices for detecting and assessing carious lesion-related conditions. Over the last 4 to 5 decades, the prevalence and severity of dental caries in primary and permanent dentitions have been reduced in a number of countries based on the published studies. Despite this achievement, the prevalence and severity of dental caries remains too high at a world level. Pits and fissures in occlusal surfaces of first molars and pits in buccal surfaces of lower first molars are most vulnerable for developing a carious lesion. Dental caries is a preventable, behavioural/life-style disease that is age related and life-long. Preventing dental caries should start at mother-and-child clinics in conjunction with the available educational and health care programmes. Oral health (caries) epidemiological surveys should be held periodically. PMID- 29794447 TI - Anti-Inflammatory Effects of Vardenafil Against Cholestatic Liver Damage in Mice: a Mechanistic Study. AB - BACKGROUND/AIMS: Phosphodiesterase-5 inhibitors have beneficial effects in multiple liver diseases possibly through the reduction of oxidative stress and inflammatory response. However, these effects have not yet been examined in cholestatic liver dysfunction. Hence, this study aimed to explore the ability of vardenafil, a known phosphodiesterase-5 inhibitor, to repress lithocholic acid (LCA)-induced cholestatic liver injury and investigate the possible molecular pathways. METHODS: Male Swiss albino mice were treated with LCA (0.125 mg/g) twice daily for 7 days to induce cholestatic liver damage. Vardenafil was administered 3 days before and throughout the administration of LCA. Serum markers of hepatotoxicity and hepatic nitro-oxidative stress along with antioxidant parameters were measured, and the histopathology of liver tissues was assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target genes was examined using PCR. The activation of nuclear factor kappa-B (NF-kappaB) and the levels of inflammatory cytokines were determined. NLRP3 inflammasome and its components were studied by PCR and western blot. RESULTS: LCA induced marked cholestatic liver damage as demonstrated by increased serum transaminases, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, and bile acids. Examination of liver specimens confirmed the biochemical results. Nitro-oxidative stress parameters were significantly elevated along with reduced antioxidant capacity in hepatic tissue following LCA administration. LCA suppressed Nrf2 and its target genes and decreased the mRNA expression and binding capacity of Nrf2 as well as the mRNA expression of GCLm, GCLc, Nqo1, and HO-1. Additionally, LCA enhanced the activation of NF-kappaB, which was accompanied by elevations of inflammatory cytokines. Importantly, LCA induced the activation of NLRP3 inflammasome. LCA increased the expression of NLRP3, ASC, caspase-1, and IL-1beta genes and proteins in hepatic tissue. The activities of IL-1beta and caspase-1 were increased in the LCA group. Interestingly, vardenafil ameliorated LCA-induced hepatic injury and alleviated all biochemical, histopathological, and inflammatory parameters. CONCLUSIONS: These data elucidated the effects of Nrf2 inhibition and NLRP3 inflammasome activation in LCA-induced liver injury. The hepatoprotective activity of vardenafil in LCA-induced cholestatic damage may result from the drug's ability to activate Nrf2 signaling and prevent the activation of NLRP3, which could suppress the inflammatory responses in hepatic tissue. Thus, vardenafil can be considered a novel anti-inflammatory remedy for cholestatic liver damage. PMID- 29794448 TI - Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats. AB - BACKGROUND/AIMS: Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. METHODS: In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARgamma was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. RESULTS: In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARgamma than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. CONCLUSIONS: ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH. PMID- 29794451 TI - Intraoperative Auditory System Monitoring. AB - A new electrophysiological system for intraoperative, continuous, near-real time monitoring of cochlear nerve function through acoustic stimulation in the ear canal and recording of the evoked dorsal cochlear nucleus potentials (DNAPs) by a specially designed DNAP electrode placed directly on the brainstem is described. The system is denominated "(cerebellopontine angle) CPA Master" and is designed for hearing preservation surgery in the cerebello-pontine angle, through the retro-sigmoid or the retro-labyrinthine approach. As an additional novelty within the field, the system allows intraoperative mapping and thus precise localization of the cochlear nerve in its entire trajectory from the brainstem to the fundus of the internal auditory canal, which is a major advance in relation to atraumatic dissection of the nerve. The system can be used for surgery of all types of CPA tumors, for example, vestibular schwannomas, meningiomas and epidermoid cysts, but also for vestibular nerve section and vascular decompression. The system also allows evaluation of the electrical functionality of an anatomically intact cochlear nerve in translabyrinthine surgery, thus predicting the benefit of optional cochlear implantation. PMID- 29794452 TI - The Future of Cochlear Implant Design. AB - This chapter discusses the multifaceted future of cochlear implant design. Current research is focused on novel strategies relating to the electrode array, aiming to improve the neuronal health and spatial selectivity, and reduce the power consumption. Future design iterations will most likely improve the neuronal health by reducing insertion trauma, minimizing the inflammatory pathway that follows electrode insertion or through the use of neurotrophins or stem cells. Improvements in spatial selectivity and in speech recognition in difficult listening environments can be achieved through changes in the electrode/neural interface. Designing an array that brings the electrodes closer to neural tissue, or changing the method of stimulation with current steering or even optical or piezoelectric stimulation are discussed. Increasing the MRI compatibility is an important consideration, and devices allowing remote programming have a huge impact on worldwide provision. Technology exists to realize the elusive goal of a fully implantable cochlear implant, allowing continuous and invisible hearing. Ultimately, future technologies will be integrated to allow tailoring of implant design to the individual, thereby addressing the broad variability in user performance. At the same time, there is an urgent requirement for a high quality, low cost, mass-produced implant for the developing world. PMID- 29794453 TI - Atraumatic Restorative Treatment: Restorative Component. AB - Atraumatic restorative treatment (ART) is a method of managing dental caries based on 2 pillars: sealants for preventing carious lesions in pits and fissures, and restorations for cavitated dentine carious lesions. ART uses only hand instruments for opening/enlarging the cavity and for removing carious tissue. The amount of carious tissue that should be removed depends mainly on the cavity depth. In cavities of shallow and medium depth, carious tissue is removed up to firm dentine. In deep/very deep cavities, in which there is no sign of pulp exposure, pulp inflammation and/or history of spontaneous pain, some soft dentine can be left in the pulpal floor/wall with the aim of avoiding pulp exposure. The ART restorative method is indicated for treating single-surface cavities in primary and permanent teeth, and in multiple-surface cavities in primary teeth. Insufficient information is available to conclude on its use for treating multiple-surface cavities in permanent teeth. PMID- 29794450 TI - Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner. AB - BACKGROUND/AIMS: The degree of hepatic ischemia-reperfusion injury (HIRI) is highly relevant to the incidence of postoperative liver failure and mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to migrate to the liver and restore the damaged liver. Intravenous anesthetics are commonly used in the perioperative period; however, it is not yet known whether they have an influence on the functions of BM-MSCs and eventually affect the recovery of HIRI. METHODS: A rat model of HIRI and a hypoxia-reoxygenation (H/R) model using L02 cells were generated, and human BM-MSCs (hBM-MSCs) were injected through the portal vein or co-cultured with L02 cells in a Transwell system, respectively. Three intravenous anesthetics, namely, dexmedetomidine, midazolam, and propofol, were given as pretreatments to hBM-MSCs. Quantitative real-time PCR for growth factors (HGF, FGF, VEGF, and IGF) and a migration assay were used to detect the paracrine and migration abilities of hBM-MSCs. NF-kappaB expression was detected using an immunofluorescence method. Furthermore, three receptor inhibitors, namely, yohimbine, PK11195, and bicuculline, were given to explore whether the three anesthetics worked in a receptor-dependent manner. RESULTS: Preconditioning with dexmedetomidine and midazolam, but not propofol, enhanced the efficacy of hBM-MSCs in HIRI. Dexmedetomidine and midazolam, but not propofol, changed the paracrine spectrum and NF-kappaB p65 nuclear translocation of hBM-MSCs co cultured with L02 cells after H/R injury. All three anesthetics enhanced the migration ability of hBM-MSCs when cultured in L02 H/R conditioned medium. However, the addition of receptor antagonists resulted in an opposite tendency. CONCLUSIONS: The intravenous anesthetics dexmedetomidine and midazolam enhanced the liver protective effects of hBM-MSCs during HIRI more effectively than propofol, by binding with their receptors and regulating the paracrine effect, migration ability, and NF-kappaB p65 nuclear translocation of hBM-MSCs. PMID- 29794454 TI - The Role of the Eustachian Tube in Middle Ear Disease. AB - The Eustachian tube is a complex structure connecting the middle ear to the nasopharynx that contributes to the normal function of the middle ear. Eustachian tube dysfunction (ETD) is thought to contribute to the majority of middle ear pathology, although the mechanisms and the degree to which it contributes to middle ear disease is poorly understood. We describe the anatomy and physiology of the Eustachian tube, define ETD, discuss the methods for measuring ETD and describe recent advances in treatment. PMID- 29794455 TI - Diagnosis and Treatment of Perilymphatic Fistula. AB - Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid (perilymph)-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces. PLF is located in the round or oval window, fractured bony labyrinth, microfissures, anomalous footplate, and can occur after head trauma or barotrauma, chronic inflammation, or in otic capsule dehiscence. This clinical entity was initially proposed more than a century ago, yet it has remained a topic of controversy for more than 50 years. The difficulty of making a definitive diagnosis of PLF has caused a long-standing debate regarding its prevalence, natural history, management and even its very existence. In this present study, we will discuss the symptoms, physiological tests (focusing on vestibular assessment) and imaging studies. Referring to a previous criticism, we will share our classification of PLF into 4 categories. Furthermore, we will summarize a nationwide survey using a novel and widely used biomarker (Cochlin-tomoprotein [CTP]) for PLF diagnosis in Japan and present the results of the new diagnostic criteria. PLF is surgically correctable by sealing the fistula, and appropriate recognition and treatment of PLF can improve hearing and balance, and in turn, improve the quality of life of afflicted patients. Therefore, PLF is an especially important treatable disease for otologists. PMID- 29794456 TI - Pharmacological Issues in Hearing Rehabilitation. AB - Surgery aimed at hearing rehabilitation risks damaging residual inner ear function, especially cochlear implant surgery. Pharmacological intervention to reduce this risk has shown great promise in animal models. The challenge is to deliver medication to the appropriate part of the inner ear in appropriate concentrations for long enough to be effective. Barriers to achieving these goals include: the blood/labyrinth barrier, limiting systemic drug delivery to the inner ear, slow rates of diffusion from the base of the cochlea to the apex, limiting intratympanic delivery from the middle ear to the cochlear apex, delayed intracochlear fibrosis, requiring extended medication delivery postoperatively. Intracochlear drug delivery via a drug-eluting cochlear implantation (CI) electrode may solve many of these pharmacologic issues. It is likely that more than one medication will be necessary to maximize inner ear protection and this may include steroids and appropriate growth factors. Such protection may also be helpful for otologic surgical procedures other than CI that have lower risks to hearing. PMID- 29794457 TI - Management of Cochlear Nerve Hypoplasia and Aplasia. AB - Approximately 2% of congenital profound deafness cases are due to cochlear nerve (CN) deficiency. MRI is essential to confirm if the nerve is deficient, but because of limitations with resolution, especially when the internal auditory canal is narrowed, it is often unable to distinguish between hypoplasia and aplasia. A full audiometric test battery should always be performed, even if the MRI suggests CN aplasia, as there will sometimes be evidence of audition. Electrically evoked auditory brainstem response testing can be carried out transtympanically via the round window or using an intracochlear test electrode to help determine the status of the CN. If any test suggests the presence of a CN, then cochlear implantation (CI) should be considered. Children should be followed up closely with audiometric, electrophysiological and language assessments to determine the benefits. They may initially show benefit but fail to progress. CI results are variable and often result in poor outcomes with Categories of Auditory Perception scores of <5. Auditory brainstem implantation (ABI) can be considered when CI is contraindicated or fails to provide adequate benefit. This may provide better outcomes, but this form of surgery has greater risks and future device replacement (in case of device failure) may be complicated. Careful patient selection is required when considering ABI as significant learning difficulties make programming extremely challenging. Patients should be given the option of CI first and then ABI. A small minority of patients presenting late (around 2-3 years of age) may be candidates for simultaneous CI and ABI. PMID- 29794458 TI - No Removal and Inactivation of Carious Tissue: Non-Restorative Cavity Control. AB - Non-restorative cavity control (NRCC) is a 3-part treatment option for dentine cavities in the primary dentition, for root carious lesions and cavitated coronal smooth surface lesions. The first part is that the patient's oral hygiene procedure/habits improve and involve the exposed dentine. For this, it may be necessary to expose the cavity (second part) so that it is accessible for the toothbrush (the lesion exposure method). As long as the dentine carious lesion is diagnosed as active or there is increased risk that carious lesion activity will recur, it is advisable to support the treatment with a 38% silver diamine fluoride (SDF) or a 5% sodium fluoride (NaF) varnish therapy (third part). NRCC has advantages over traditional restorative therapy as it avoids the stress and fear initiation that often results from invasive restorative therapy. It avoids a futile or detrimental repeat restorative cycle when cavity outlines have to be designed in caries active areas and it increases awareness of people's own responsibility for oral health and the quality of the oral hygiene procedure. NRCC has been advocated, particularly in primary dentitions, for patients or parents/carers who are able to accept responsibility for the disease and commit to remedial action including diet modification and regular, frequent toothbrushing with a fluoride toothpaste. It should not be used when immediate invasive action is required such as in the case of pain, infection, or sepsis, or where there is no readiness to change behaviours that have led to the development of the disease in the first place. Professionals who choose NRCC commit themselves to being critical regarding their educational qualities and to commence a cycle of quality improvement. PMID- 29794459 TI - Hearing Rehabilitation in Neurofibromatosis Type 2. AB - Bilateral vestibular schwannomas are almost pathognomonic of neurofibromatosis type 2 (NF2). As a result of these tumors, hearing loss is the presenting symptom in 60% of adults and 30% of children with NF2. It is often bilateral. The best means of preserving hearing in patients with NF2 is conservative management. Even so at least 28% of patients have progression of hearing loss following diagnosis. The likelihood of progression of hearing loss is, at least in part, determined by the type of mutation. Treatment of vestibular schwannomas often has a detrimental effect on hearing. Only 41% of patients having stereotactic radiosurgery maintain their hearing at 5 years. Treatment with bevacizumab maintains medium-term hearing in 38% and improves it in 48%. Surgery to remove vestibular schwannomas invariably leads to complete loss of ipsilateral hearing, although in a very limited number of patients hearing preservation surgery may be possible. For those that lose their hearing but have an intact cochlear nerve, for example, conservative management, radiotherapy treatment or cochlear nerve preserving surgery, cochlear implantation has been shown to be an effective option although outcomes are not as good as traditional implant candidates (mean sentence testing scores in quiet: stable untreated tumors 69%; radiotherapy treated tumors 49%; cochlear nerve preserving surgery ~40%). For those that do not have a functional cochlear nerve, auditory brainstem implantation (ABI) is an option. The non-user rate in this group is 13%. The mean sentence score in users with ABI alone is 12%. ABI therefore acts, in most cases, as an aid to lip reading and rarely provides open set speech discrimination. PMID- 29794460 TI - Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2. AB - BACKGROUND/AIMS: Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. METHODS: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen's method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. RESULTS: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. CONCLUSION: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI. PMID- 29794461 TI - The CCL5/CCR5 Axis Promotes Vascular Smooth Muscle Cell Proliferation and Atherogenic Phenotype Switching. AB - BACKGROUND/AIMS: Hyperlipidemia induces dysfunction in the smooth muscle cells (SMCs) of the blood vessels, and the vascular remodeling that ensues is a key proatherogenic factor contributing to cardiovascular events. Chemokines and chemokine receptors play crucial roles in vascular remodeling. Here, we examined whether the hyperlipidemia-derived chemokine CCL5 and its receptor CCR5 influence vascular SMC proliferation, phenotypic switching, and explored the underlying mechanisms. METHODS: Thoracoabdominal aorta were isolated from wild-type, CCL5 and CCR5 double-knockout mice (CCL5-/-CCR5-/-) fed a high-fat diet (HFD) for 12 weeks. Expression of the contractile, synthetic, and proliferation markers were assayed using immunohistochemical and western blotting. The effects of CCL5 and palmitic acid on cultured SMC proliferation and phenotypic modulation were evaluated using flow cytometry, bromodeoxyuridine (BrdU), and western blotting. RESULTS: Wild-type mice fed an HFD showed markedly increased total cholesterol, triglyceride, and CCL5 serum levels, as well as significantly increased CCL5 and CCR5 expression in the thoracoabdominal aorta vs. normal-diet-fed controls. HFD fed CCL5-/-CCR5-/- mice showed significantly decreased expression of the synthetic phenotype marker osteopontin and the proliferation marker proliferating cell nuclear antigen, and increased expression of the contractile phenotype marker smooth muscle alpha-actin in the thoracoabdominal aorta vs. wild-type HFD fed mice. Human aorta-derived SMCs stimulated with palmitic acid showed significantly increased expression of CCL5, CCR5, and synthetic phenotype markers, as well as increased proliferation. CCL5-treated SMCs showed increased cell cycle regulatory protein expression, paralleling increased synthetic and decreased contractile phenotype marker expression. Inhibition of CCR5 activity by the specific antagonist maraviroc or its expression using small interfering RNA significantly inhibited human aortic SMC proliferation and synthetic phenotype formation. Therefore, CCL5 induces SMC proliferation and phenotypic switching from a contractile to synthetic phenotype via CCR5. CCL5-mediated SMC stimulation activated ERK1/2, Akt/p70S6K, p38 MAPK, and NF-kappaB signaling. NF-kappaB inhibition significantly reduced CCR5 expression along with CCR5-induced SMC proliferation and synthetic phenotype formation. CONCLUSIONS: Hyperlipidemia induced CCL5/CCR5 axis activation serves as a pivotal mediator of vascular remodeling, indicating that CCL5 and CCR5 are key chemokine-related factors in atherogenesis. SMC proliferation and synthetic phenotype transformation attenuation by CCR5 pharmacological inhibition may offer a new approach to treatment or prevention of atherosclerotic diseases associated with hyperlipidemia. PMID- 29794462 TI - Long Non-Coding RNA Emergence During Renal Cell Carcinoma Tumorigenesis. AB - Renal cell carcinoma (RCC) is the most common kidney cancer diagnosed across the globe and has steadily increased in incidence in recent decades. Techniques for diagnosing or treating RCC are limited, and confined mostly to later stages of the disease. Almost all RCC pathological types are resistant to chemotherapeutics and radiation therapy. To this effect, new markers for diagnosis and target therapy are urgently needed. Advanced genome sequencing technologies have revealed long non-coding RNAs (lncRNAs) as a novel marker, transcribed throughout the human genome. The emergence of lncRNAs is an aberrant expression and is involved in the tumorigenesis of RCC. LncRNAs drive cancer phenotypes through their interaction with other cellular macromolecules including DNA, protein, and RNA. Recent research on lncRNA molecular mechanisms has revealed new markers to functionally annotate these cancers' associated transcripts, making them targets for effective diagnosis and therapeutic intervention in the fight against cancer. In this review, we first highlight the common mechanisms that underlie aberrant lncRNA expression in RCC. We go on to discuss the potential translational application of lncRNA research in the diagnosis, prognosis, and treatment of RCC. PMID- 29794464 TI - Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients. AB - BACKGROUND/AIMS: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. METHODS: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. RESULTS: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. CONCLUSION: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early stage colorectal carcinoma. PMID- 29794463 TI - Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product Induced M2 to M1 Macrophage Polarization. AB - BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. METHODS: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-gamma + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. RESULTS: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. CONCLUSIONS: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process. PMID- 29794465 TI - Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy. AB - Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a membrane glycoprotein expressed by activated effector T cells (Teffs) and participates in the repression of T cell proliferation, cell cycle progression and cytokine production. Currently, antibodies targeting CTLA-4, ipilimumab and tremelimumab are widely used as a therapeutic approach in a variety of human malignancies. However, their detailed mechanism remains unclear. Therefore, in this review, we focused specifically on recent findings concerning the role of CTLA-4 in immune response and also discussed clinical studies of targeting CTLA-4, alone or in combination with other therapies for the treatment of cancers. CTLA-4 blockade is used as a therapeutic approach for the treatment of cancer through competing with CD28-positive costimulation for binding to their shared B7 ligands or exhibiting direct inhibitory effect on signaling molecules in the cytoplasmic tail. At present, antibodies for targeting CTLA-4 or in combination with other therapies significantly reinforced the anti-tumor effect and improved the prognosis of malignant disease. In addition, severe adverse events of targeting CTLA-4 therapy could be a challenge for the development of this therapeutic strategy. This review may provide some new insights for clinical studies of targeting CTLA-4. PMID- 29794467 TI - Caries Excavation: Evidence Gaps. AB - Dental caries, the most common chronic disease in the world, affects over 3 billion people globally. Its management comprises a large proportion of dental care providers' clinical responsibility, yet despite the extensive evidence base for the management of cavitated carious lesions, gaps in the evidence persist. This promotes uncertainty and debate among providers. This chapter reiterates the 3 key components of evidence-based practice (EBP): clinical expertise, an awareness and appreciation of patient values, and use of best available evidence. Secondly, we give a brief summary of current best evidence pertaining to some key areas of caries excavation in the context of lesion management, and highlight respective gaps in the evidence. Consideration is given to the state of the evidence for: how carious-lesion excavation is best achieved, the extent to which excavation should occur, contemporaneous practice, the timing of dental intervention in relation to the extent of the disease, and some areas of contention. Finally, there is discussion around how dental care providers might proceed when high-quality evidence does not exist to inform that part of the EBP collective. PMID- 29794466 TI - Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer. AB - BACKGROUND/AIMS: Metastasis is the primary cause of colorectal cancer (CRC) related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. METHODS: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. RESULTS: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced "CRC cell" migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. CONCLUSIONS: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC. PMID- 29794469 TI - Sealing Carious Tissue in Primary Teeth Using Crowns: The Hall Technique. AB - In line with reducing the invasiveness of interventions in permanent teeth and changes towards more biological approaches, there have also been moves away from traditional restorative approaches to managing primary teeth where carious dentine/lesions were completely excised and a restoration placed. The Hall Technique is a method for managing carious primary molar teeth where a preformed stainless-steel crown, also known as a preformed metal crown, is seated over a tooth, sealing in, and not removing carious tissue. This chapter discusses the rationale behind the Hall Technique, an outline of the clinical procedure to carry it out, its indications and contraindications, together with the evidence supporting its use. The Hall Technique has been found to be acceptable to children and preferred to more invasive treatment options. Like all dental treatment options, it requires careful case selection, precise carious lesion and pulpal status diagnosis (clinically and radiographically), good patient management, and excellent parental cooperation. The Hall Technique has been shown to be a durable (being likely to last the lifespan of the primary molar) and economical management option for primary molars with carious lesions, which in addition offers the benefit of full coronal coverage, reducing the risk of future carious lesion development. As part of our everyday armamentarium in paediatric dentistry, the Hall Technique is an effective management option for controlling carious lesions in primary molars. PMID- 29794468 TI - Allicin Inhibits Proliferation and Invasion in Vitro and in Vivo via SHP-1 Mediated STAT3 Signaling in Cholangiocarcinoma. AB - BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is a malignant tumor that is resistant to chemotherapy, so new therapeutic agents are needed. Allicin which is rapidly converted from allin by allinase, is one of the most biologically active compounds in freshly crushed garlic and has been shown to have strong anti-tumor effects. Our aim was to explore the molecular mechanism by which allicin affects the cell proliferation and invasion of CCA. METHODS: Cell viability and apoptosis were measured using the CCK-8 assay, colony formation assay, and flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell assays, respectively. The expression of several proteins involved in cell apoptosis and invasion were assessed by Western blot. The activation of STAT3 signaling was detected by Western blot and immunofluorescence staining. The involvement of SHP 1 was determined using small interfering RNA (siRNA). Moreover, a nude mouse model of human CCA was established to assess the anti-tumor effects of allicin in vivo. RESULTS: Allicin significantly suppressed CCA cell proliferation by activating the caspase cascade, inducing apoptosis, and reducing the expression of proteins downstream of STAT3, such as B-cell lymphoma 2 (Bcl-2), while upregulating Bcl-2-associated X (Bax) protein. In addition, allicin inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. Moreover, the protein expression of MMP-2 and MMP-9 was significantly downregulated in CCA cells treated with allicin compared with CCA cells treated with control. Mechanistic investigations indicated that allicin upregulated SHP-1 expression in CCA, and pervanadate treatment reversed the allicin-induced downregulation of STAT3. Moreover, suppression of SHP-1 by siRNA overturned the effect of allicin on the induction of SHP-1 and inhibition of STAT3 activation. Additionally, treatment with allicin attenuated tumor growth in the nude mouse model of CCA. CONCLUSIONS: Our findings suggest that allicin suppresses cell proliferation and invasion via STAT3 signaling and may be a potential therapeutic agent for CCA. PMID- 29794471 TI - Optical Coherence Tomography Angiography in Glaucoma: A Review. AB - BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. Several techniques exist for the diagnosis and follow-up of patients. Optical coherence tomography (OCT) angiography (OCTA) is a recently developed technique that provides a quantitative assessment of the microcirculation of the retina and choroid in a fast, noninvasive way. Despite it being a novel technique, several publications have already been done in the glaucoma field. However, a summary of findings is currently lacking. AIMS: To perform a literature review to assess the role of OCTA in glaucoma diagnosis and follow-up. METHODS: A database search was carried out using MEDLINE, Embase, and Web of Science, including all original works registered until July 23, 2017. RESULTS: OCTA (1) has a high repeatability and reproducibility, (2) has good discriminatory power to differentiate normal eyes from glaucoma eyes, (3) is more strongly correlated with visual function than conventional OCT, (4) has good discriminatory power to differentiate early glaucoma eyes from normal eyes (i.e., at least equal to that of OCT), (5) reaches a floor effect at a more advanced disease stage than OCT, and (6) is able to detect progression in glaucoma eyes. CONCLUSION: OCTA shows potential to become a part of everyday glaucoma management. PMID- 29794472 TI - An Agreed Terminology for Carious Tissue Removal. AB - Understanding the carious process as a biofilm disease rather than an infectious disease has changed lesion management focus towards less invasive options. This has led to new and ongoing changes in recommendations for practitioners. However, the lack of clarity over what to do, and when, is complicated by different teaching, research, and policy documents containing different terms and definitions for carious lesions and management strategies. Lack of clear messages and communication over recommendations hampers moving evidence into practice. The International Caries Consensus Collaboration (ICCC) recommendations on terminology are one part of improving communication for discussing the diagnosis and management of dental caries and dental carious lesions. The term dental caries is the name of the disease, its use being limited to situations involving control of the disease using preventive and noninvasive measures at the patient level. Carious lesion management should be used where management is directly related to disease symptoms at the tooth level. As terminology cannot be used to directly relate the visual appearance of the carious lesion to the histopathology, the terms have been based around the clinical consequences of the disease: soft, leathery, firm and hard dentine. The 3 main carious tissue removal options are described as: (1) selective removal of carious tissue (to both soft and firm dentine), (2) stepwise removal, and (3) non-selective removal to hard dentine (previously known as complete removal and no longer recommended). Use of these terms across clinicians, researchers, dental educators, and even with patients, will help improve understanding and communication. PMID- 29794470 TI - Matrix Metalloproteinases-3 Baseline Serum Levels in Early Rheumatoid Arthritis Patients without Initial Radiographic Changes: A Two-Year Ultrasonographic Study. AB - OBJECTIVE: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naive rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. METHODS: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti rheumatic drugs/glucocorticoid naive patients (mean age 53.4 +/- 14.1) with symptom duration <=12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. RESULTS: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23-18.9], p = 0.024; OR 1.17 [0.320-4.26], p = 0.816 respectively). CONCLUSION: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3 positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints. PMID- 29794473 TI - MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL. AB - BACKGROUND/AIMS: In this study, the molecular mechanisms of miR-27b and lipoprotein lipase (LPL) that regulate human adipose-derived mesenchymal stem cells (hASCs) adipogenic differentiation were detected. METHODS: Microarray analysis was applied to screen for differentially expressed miRNAs and mRNA during hASCs adipocyte differentiation induction. MiR-27b and LPL were found to have abnormal expression. Then, a dual luciferase reporter assay was employed to validate the targeting relationship between miR-27b and LPL. We also utilized qRT PCR, western blot, cellular immunofluorescence and an oil red O staining assay to analyze the regulation of miR-27b and LPL during adipogenic differentiation. RESULTS: The microarray analysis demonstrated that, during adipogenic differentiation, miR-27b was down-regulated, while LPL was up-regulated but tended to become stable 14 days after induction. A dual luciferase reporter assay confirmed the negative targeting regulatory relationship between miR-27b and LPL. After overexpressing and silencing miR-27b, LPL was found to be reversely regulated by miR-27b according to qRT-PCR and western blot. The fat-formation related biomarkers CCAAT-enhancer binding protein alpha (c/EBPalpha) and peroxisome proliferator-activated receptors gamma (PPARgamma) had decreasing levels after over-expressing miR-27b or knockdown of LPL followed by adipogenic differentiation. Meanwhile, the oil red O staining assay revealed that the accumulation of lipid droplets decreased. There was no change in the expression of c/EBPalpha, PPARgamma, or lipid droplet accumulation when overexpressing miR 27b and LPL. CONCLUSION: During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. PMID- 29794475 TI - Selective Removal of Carious Tissue. AB - Describing and quantifying how much carious tissue should be removed prior to placing a restoration has been a long-debated issue stretching back as far as G.V. Black's "complete caries removal," now known as non-selective carious tissue removal. Originating in the 1960s and 1970s, from the differentiation between different layers of carious dentine, an outer contaminated ("infected") layer and an inner demineralised ("affected") layer, the former of which needed to be removed during cavity preparation and the latter not, selective carious tissue removal was born. Currently, it is termed selective removal to firm dentine. This chapter describes different selective carious tissue removal techniques (to firm, to leathery, to soft dentine) and how they can be achieved appropriately with conventional and novel techniques. Selective removal to firm dentine is recommended for shallow or moderately deep lesions, while for deep lesions (extending close to the pulp) in teeth with vital pulps, selective removal to soft dentine is recommended to avoid pulpal exposure and to preserve the health of the pulp. Leaving soft carious dentine beneath a restoration does, however, raise certain issues regarding how we truly assess pulpal health, what would other dental practitioners think if the patient moved practice, and how do we monitor such sealed residual caries in the future. These issues will all be discussed in this chapter but should at present not preclude dental practitioners from adopting such a minimally invasive evidence-based approach to carious tissue removal. PMID- 29794474 TI - Stabilization of Slug by NF-kappaB is Essential for TNF-alpha -Induced Migration and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cells. AB - BACKGROUND/AIMS: Slug protein, a transcription factor for the induction of epithelial-mesenchymal transition (EMT) and cancer cell invasion and metastasis, is frequently upregulated in human epithelial cancers. However, mutation of this gene in cancer is rare, and the mechanism of its dysregulation remains unknown, especially in head and neck squamous cell carcinoma (HNSCC). METHODS: We examined the role of TNF-alpha in the stabilization of Slug by immunoprecipitation westernblot analysis. Migration of HNSCC cells with or without knockdown of Slug gene expression was assayed by a wound healing assay. Immunohistochemical staining analysis was used to measurement Slug levels in both normal and HNSCC tumor tissues. RESULTS: The inflammatory cytokine TNF-alpha stabilized Slug protein by inhibiting its ubiquitination through the NF-kappaB pathway. Inhibition of NF-kappaB or knockdown of p65 abrogated the TNF-alpha-induced stabilization of Slug. Knockdown of Slug expression inhibited cancer cell migration and EMT characteristics induced by TNF-alpha. Moreover, increased levels of Slug were found to correlate with lymph node metastasis and predict poor prognosis in patients with HNSCC. CONCLUSIONS: NF-kappaB-mediated stabilization of Slug underlies the inflammation-induced EMT and metastasis in HNSCC, which may serve as a therapeutic target for metastatic HNSCC. PMID- 29794477 TI - Evidence-Based Deep Carious Lesion Management: From Concept to Application in Everyday Clinical Practice. AB - This chapter aims to discuss the way dental practitioners manage deep carious lesions (DCL) in routine practice and the barriers and incentives/facilitators to changes in accepted practice. In concert with the philosophy of minimal intervention dentistry, the concept of quaternary prevention (actions taken to prevent overtreatment and reduce harm to the patient) emerges in dentistry. This can be applied to carious tissue removal (CTR) in DCL given the risks associated with this procedure (high risk of pulp exposure, pulpal complications, tooth substance loss, and unsuccessful invasive, expensive outcomes). Recently conducted questionnaire surveys show that a gap exists between research findings and professional practices in relation to DCL management. It is, therefore, important to identify the barriers to the implementation of evidence-based dentistry into dental practices for the management of DCL in order to create appropriate corrective interventions to encourage practitioners in the use of selective CTR as a procedure. PMID- 29794476 TI - Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas. AB - BACKGROUND/AIMS: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). METHODS: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. RESULTS: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient' survival was then validated using the CGGA dataset. Moreover, Kaplan Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild type gliomas. CONCLUSION: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials. PMID- 29794478 TI - Carious Lesion Diagnosis: Methods, Problems, Thresholds. AB - The difference between carious lesion diagnosis and carious lesion detection is discussed here. Concerning carious lesions, 3 diagnostic requirements should be fulfilled: to detect lesions, to assess surface integrity, and to assess lesion activity to support clinical decision making. The first and most important diagnostic method is meticulous visual-tactile inspection. This is the only method that potentially contributes to all 3 diagnostic requirements. All other methods that are presented in this chapter, i.e., bitewing radiography, fluorescence-based technologies, and transillumination methods, are limited to assessing lesion depth in surfaces that are not visible to the eye and thus contribute to lesion detection only. At the end of the chapter, recent developments in objective lesion activity assessment are presented. PMID- 29794479 TI - Hearing Preservation Cochlear Implant Surgery. AB - Cochlear implantation (CI), with attempted preservation of residual natural low frequency hearing, is an increasingly accepted application of this technology, with potential benefits to the patient when listening in noise and in music appreciation. The full extent of the benefits of combining preserved natural hearing and electrical stimulation remain under evaluation. Various factors appear to influence the success of hearing preservation (HP) during CI, including electrode design, surgical approach, insertional trauma, steroid usage and patient factors. Currently, combining or contrasting outcomes of CI with attempted HP is difficult due to the use of heterogeneous outcome measures. Until we have a full understanding of the benefits of preserving residual low-frequency hearing during CI, there is merit in attempting to preserve all residual hearing. Likewise, preserving residual low-frequency hearing is a useful surrogate marker for atraumatic electrode design and insertion. PMID- 29794481 TI - Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study. AB - BACKGROUND/AIMS: Ultrasound-guided supraclavicular brachial plexus block (BPB) has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB. METHODS: The study involved 90 adults divided into three groups: control (bupivacaine), midazolam (bupivacaine plus midazolam), and neostigmine (bupivacaine plus neostigmine). Blood samples were taken and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated. RESULTS: Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-alpha mRNA levels. CONCLUSION: Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects. PMID- 29794483 TI - Dual-Positive CD4/CD8 Primary Cutaneous Peripheral T-Cell Lymphoma Previously Classified as Mycosis Fungoides a Tumor D'Emblee. AB - Cutaneous peripheral T-cell lymphoma, not otherwise specified represents a "waste basket" of all cases that cannot be put into another of the categories of mature cutaneous T-cell lymphoma. Previously, the sudden multifocal development of cutaneous CD4 tumors without preceding a patch or plaque stage was classified as d'emblee form of mycosis fungoides (MF). Currently, the term "MF" reserved only for the classic Alibert-Bazin type characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. The authors describe a 75-year-old white woman who presented with a solitary skin tumor in the right supraclavicular region, with no lymph node or systemic involvement. Local external beam radiation treatment resulted in a complete response. The patient relapsed after 5 months with new tumors in the left neck and left upper chest. Biopsy of the lesions showed a dermal infiltrate of atypical small- to medium-sized T-lymphocytes, and immunohistochemical staining showed coexpression of CD4/CD8 in a subset of these cells, which was confirmed with flow cytometry of the tumor. Although the patient had no preceding patch or plaque stage, the authors herein report this extremely rare case of CD4/CD8 dual positive peripheral T-cell lymphoma, not otherwise specified presented as MF d'emblee and discuss the seldom similar cases published previously. PMID- 29794480 TI - Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer. AB - BACKGROUND/AIMS: Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. METHODS: Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-beta-smad2/3 pathway by interacting with TGFbetaR2. RESULTS: MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-beta-smad2/3 pathway by interacting with TGFbetaR2. Inhibition of TGF-beta-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-beta induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-beta induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-beta-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. CONCLUSIONS: These findings suggested that TGFbetaR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer. PMID- 29794484 TI - Nevus Trichilemmocysticus: a Mild Case. PMID- 29794485 TI - Alternatives for Peripheral Nerve Repair. PMID- 29794482 TI - Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Steroid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial. AB - BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) may be beneficial for clinical remission during conventional therapy with tonsillectomy and steroid pulse (TSP) for active IgA nephropathy. METHODS: Seventy-seven patients with active IgA nephropathy were randomly assigned to the control arm with conventional regimen (TSP followed by oral prednisolone) (n = 37) or the ARB arm with conventional regimen plus ARB candesartan for the first 6 months (n = 40). Patients not achieving proteinuria remission at 12 months in either arm were administered candesartan, which was titrated until the 24-month follow-up. The primary endpoints were remission of proteinuria (< 0.3 g/gCr) and hematuria at 12 months. RESULTS: Baseline proteinuria (g/g Cr) were comparable between the control and ARB arm (1.02 vs. 0.97, P = 0.97). Similarly, cumulative remission rates at 6, 12, and 24 months were comparable between the control and ARB arms (37.8% vs. 35% [P = 0.80], 48.7% vs. 38.5% [P = 0.37], 71.4% vs. 51.3% [P = 0.08]). Proteinuria, which was slightly worse in the control arm than in the ARB arm at 6 months, was comparable afterwards (0.20 vs. 0.23 g/g Cr at 12 months; 0.12 vs. 0.13 g/g Cr at 24 months). Significant reductions observed in urinary angiotensinogen were almost comparable between the two treatment arms at both 6 and 12 months. CONCLUSION: Early candesartan treatment combined with TSP may not benefit clinical remission regardless of the blood pressure. ARB titration later during the treatment might provide benefit for patients with active IgA nephropathy. PMID- 29794486 TI - Isolated Iliac Crest Tuberculosis: A Case Report. AB - CASE: Following an insidious onset of symptoms, a 29-year-old man who had no risk factors for tuberculosis was diagnosed with tuberculosis of the iliac crest. The red flag in this case was the patient's progressive deterioration despite a variety of antibiotic regimens. Histopathologic demonstration of necrotic granulomatous inflammation and a positive culture led to the diagnosis. A combination of surgery and antitubercular-drug therapy resulted in clinical recovery. CONCLUSION: Iliac crest tuberculosis represents <1% of all skeletal tuberculosis cases. Even in the absence of classic symptoms and risk factors, orthopaedic surgeons should maintain a low threshold for tuberculosis in the differential diagnosis. PMID- 29794487 TI - Use of a Total Shoulder Arthroplasty in a Patient with Minimally Painful Severe Glenohumeral Arthritis and a Progressive Plexopathy: A Case Report. AB - CASE: A 70-year-old woman presented with severe but minimally painful right glenohumeral osteoarthritis (OA), with progressive weakness and numbness radiating to the right hand. Imaging revealed a large fluid collection extending from the joint to the subcoracoid space, with a mass effect on the brachial plexus. A total shoulder arthroplasty (TSA) and decompression of a ganglion cyst were performed. Follow-up with serial electromyography demonstrated resolution of the brachial plexopathy and restoration of function. CONCLUSION: Ganglion cysts may arise secondary to severe glenohumeral OA and may compress the surrounding structures, producing a progressive plexopathy. Treatment of the underlying pathology with a TSA may be effective. PMID- 29794488 TI - Life-Threatening Hemorrhage from an Unrecognized Axillary Vein Injury During Treatment of a Proximal Humeral Fracture-Dislocation with a Known Axillary Artery Injury: A Case Report. AB - CASE: A 57-year-old man presented with bilateral proximal humeral fracture dislocation and an associated axillary artery injury. He was treated urgently with reduction, arterial repair, fasciotomies, and skeletal stabilization. The patient sustained a massive intraoperative hemorrhage from an unrecognized axillary vein injury after the arterial repair. CONCLUSION: An unrecognized axillary vein injury led to substantial blood loss that required a massive transfusion protocol. Although an axillary arterial injury is readily identified with computed tomography angiography, concomitant venous injuries may go unrecognized. The surgical team, including the vascular and orthopaedic surgeons and the anesthesiologists, should be prepared to manage a life-threatening hemorrhage. PMID- 29794490 TI - Erratum: Isolated Scapular Metastasis in a Patient with Malignant Struma Ovarii. PMID- 29794489 TI - Tibial Plateau Fracture Following Anterior Cruciate Ligament Reconstruction with a Bone-Patellar Tendon-Bone Allograft: A Case Report. AB - CASE: A 36-year-old woman sustained a medial tibial plateau fracture involving a tibial tunnel that had been used 4 years prior for an anterior cruciate ligament (ACL) reconstruction with a bone-patellar tendon-bone (BPTB) allograft in the same knee. At 26 months following open reduction and internal fixation of the tibial plateau fracture (6 years following the index ACL reconstruction), the patient returned to full activity. CONCLUSION: To our knowledge, this is the first report of a tibial plateau fracture following ACL reconstruction with a BPTB allograft, which adds to the paucity of literature discussing tibial plateau fractures following ACL reconstruction and discusses the potential predisposing factors to fracture such as ACL graft selection and surgical technique. PMID- 29794491 TI - Adolescent age is an independent risk factor for abnormal spirometry among people living with HIV in Kenya. AB - OBJECTIVES: As life expectancy of people living with HIV (PLWH) improves in low income and middle-income countries (LMICs), the spectrum of HIV-related pulmonary complications may reflect a greater burden of chronic lung diseases as in high income countries. We determined whether the risk of abnormal spirometry was greater among adolescent compared with adult PLWH at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya, and evaluated the role of other cofactors for abnormal spirometry. DESIGN: We prospectively enrolled adolescent and adult PLWH for this cross-sectional study. METHODS: Data collection included standardized questionnaires, clinical assessment, and prebronchodilator and postbronchodilator spirometry. Adolescents additionally underwent noncontrast chest computed tomography. Multivariable logistic regression determined associations of adolescent age with abnormal spirometry, adjusting for cofactors. RESULTS: Of 427 PLWH, 21 (40%) adolescents and 64 (17%) adults had abnormal spirometry. Among adolescents, 80% had abnormal chest CTs, and 79% had at least one respiratory symptom. Adolescent age (adjusted odds ratio 3.22; 95% confidence interval 1.48-6.98) was independently associated with abnormal spirometry, adjusting for recent CD4, HIV clinical stage, low BMI, indoor kerosene use, smoking pack-years, and prior pulmonary tuberculosis. Additional important cofactors for abnormal spirometry included prior pulmonary tuberculosis (3.15; 1.70-5.58), kerosene use (1.77; 1.04-3.04) and smoking pack-years (1.05; 1.00 1.10). Adolescent age, prior pulmonary tuberculosis, and smoking pack-years were significantly associated with airflow limitation. CONCLUSION: Adolescent age was independently associated with increased risk of abnormal spirometry, particularly airflow limitation. Studies to improve prevention, detection, and management of chronic lung disease across the lifespan among PLWH are needed in LMICs. PMID- 29794493 TI - Per-partner condom effectiveness against HIV for men who have sex with men. AB - OBJECTIVE: Few studies have examined condom effectiveness for HIV prevention among MSM. We estimated condom effectiveness per partner in four cohorts of MSM during 1993-2003 (JumpStart, Vaccine Preparedness Study, VAX004 and Project Explore). METHODS: We used logistic regression to estimate the increase in odds of new HIV infection per HIV-positive partner for condom-protected receptive anal intercourse (PRAI; partners with whom condoms were always used) and condomless (unprotected) receptive anal intercourse (URAI; partners with whom condoms were sometimes or never used). To estimate condom effectiveness for preventing HIV transmission, we applied the concept of excess odds, the odds ratio minus 1. The condom failure rate was estimated as the excess odds per PRAI partner divided by the excess odds per URAI partner. Condom effectiveness was then 1 minus the failure rate. RESULTS: The excess odds of HIV infection per HIV-positive partner were 83% for URAI and 7% for PRAI. The resulting failure rate (9%) indicated per partner condom effectiveness of 91% (95% confidence interval 69-101). CONCLUSION: The increase in odds of new HIV infection per HIV-positive partner for receptive anal intercourse was reduced by 91% for each partner with whom condoms were always used. PMID- 29794492 TI - Antiretroviral drug use and HIV drug resistance among MSM and transgender women in sub-Saharan Africa. AB - OBJECTIVE: To analyze antiretroviral drug use and HIV drug resistance among HIV infected MSM and transgender women who were screened for participation in the HIV Prevention Trials Network 075 study. METHODS: A qualitative assay was used to detect 20 antiretroviral drugs in five drug classes; this assay is based on liquid chromatography coupled with high-resolution accurate-mass mass spectrometry. HIV viral load testing was performed using the RealTime HIV-1 Viral Load Assay. HIV drug resistance testing was performed using the ViroSeq HIV-1 Genotyping System. Logistic regression was used to evaluate factors associated with study outcomes. RESULTS: Antiretroviral drugs were detected in 63 (34.4%) of 183 participants who had confirmed HIV infection at screening; 11 (17.5%) of the 63 participants were not virally suppressed. Six (54.5%) of the 11 participants had drug-resistant HIV, including four who had multiclass resistance. Seven (63.6%) of the 11 were at risk of acquiring resistance to additional antiretroviral drugs. In multivariate model, antiretroviral drugs were more frequently detected in older participants, those recruited from Kisumu, Kenya, and those who reported ever having been in HIV care or on antiretroviral therapy (ART). CONCLUSION: Most of HIV-infected persons screened for participation in HIV Prevention Trials Network 075 were not on ART, and many of those who were on ART were not virally suppressed. Many of those participants had drug-resistant HIV. These findings highlight the need for improved HIV care for African MSM and transgender women. PMID- 29794494 TI - Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV. AB - OBJECTIVE: The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body composition among adult men with HIV and without HIV. DESIGN/METHODS: Men with and without HIV (age 50-69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition [BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis]. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition. RESULTS: A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20). CONCLUSION: Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting. PMID- 29794496 TI - Neuromodulation in Pediatrics: Case Series. AB - OBJECTIVES: Neuromodulation, particularly intrathecal drug delivery systems and spinal cord stimulators (SCSs), can be a valuable tool when treating chronic pain in adults. However, there is a paucity of literature with regard to its use in pediatrics. MATERIALS AND METHODS: We present a series of 14 children and adolescents with intractable pain who received a SCS or a pump for the intrathecal delivery of medications between 2010 and 2016 at our institution. RESULTS: During the study period, we placed 10 intrathecal pumps and 4 SCSs with an average age of 17 years old. Pain scores significantly improved after the implant (P<0.007) and function improved in 79% of patients. Opioid use was also significantly reduced. Three patients eventually had their device removed due to psychiatric comorbidities. Four patients had complications that were treated without further sequelae. CONCLUSIONS: Neuromodulation can offer important options in treating some pediatric chronic pain patients. In-depth knowledge of primary disease and strict patient selection in the context of the patient's social situation is vital to successful treatment. PMID- 29794495 TI - Global population-level association between herpes simplex virus 2 prevalence and HIV prevalence. AB - BACKGROUND: Our objective was to assess the population-level association between herpes simplex virus 2 (HSV-2) and HIV prevalence. METHODS: Reports of HSV-2 and HIV prevalence were systematically reviewed and synthesized following PRISMA guidelines. Spearman rank correlation ((Equation is included in full-text article.)) was used to assess correlations. Risk ratios (RRHSV-2/HIV) and odds ratios (ORHSV-2/HIV) were used to assess HSV-2/HIV epidemiologic overlap. DerSimonian-Laird random-effects meta-analyses were conducted. RESULTS: In total, 939 matched HSV-2/HIV prevalence measures were identified from 77 countries. HSV 2 prevalence was consistently higher than HIV prevalence. Strong HSV-2/HIV prevalence association was found for all data ((Equation is included in full-text article.) = 0.6, P < 0.001), all data excluding people who inject drugs (PWID) and children ((Equation is included in full-text article.) = 0.7, P < 0.001), female sex workers ((Equation is included in full-text article.) = 0.5, P < 0.001), and MSM ((Equation is included in full-text article.) = 0.7, P < 0.001). No association was found for PWID ((Equation is included in full-text article.) = 0.2, P = 0.222) and children ((Equation is included in full-text article.) = 0.3, P = 0.082). A threshold effect was apparent where HIV prevalence was limited at HSV-2 prevalence less than 20%, but grew steadily with HSV-2 prevalence for HSV-2 prevalence greater than 20%. The overall pooled mean RRHSV-2/HIV was 5.0 (95% CI 4.7-5.3) and ORHSV-2/HIV was 9.0 (95% CI 8.4-9.7). The RRHSV-2/HIV and ORHSV 2/HIV showed similar patterns that conveyed inferences about HSV-2 and HIV epidemiology. CONCLUSION: HSV-2 and HIV prevalence are strongly associated. HSV-2 prevalence can be used as a proxy 'biomarker' of HIV epidemic potential, acting as a 'temperature scale' of the intensity of sexual risk behavior that drive HIV transmission. HSV-2 prevalence can be used to identify populations and/or sexual networks at high-risk of future HIV expansion, and help prioritization, optimization, and resource allocation of cost-effective prevention interventions. PMID- 29794497 TI - SGLT inhibition: a possible adjunctive treatment for type 1 diabetes. AB - PURPOSE OF REVIEW: To identify and evaluate the recent trials of sodium-glucose cotransporter 1 and 2 (SGLT1 and SGLT2, respectively) inhibitor use in patients with type 1 diabetes (T1D). SGLT-2 inhibitors have been approved by the Food and Drug Administration (FDA) and are effectively used in the treatment of type 2 diabetes (T2D). However, many studies (phase I-III) have validated their effects beyond improving glycemic control and have shown potential adjunctive use in adult patients with T1D treated with insulin therapy alone. RECENT FINDINGS: A review of the literature showed that there is a potential adjunctive role for the SGLT inhibitors with insulin in T1D for improving glycemic control. The inTandem3 (A phase III study to evaluate the safety of sotagliflozin in patients with type 1 diabetes who have inadequate glycemic control with insulin therapy alone) and the DEPICT-1 (Dapagliflozin evaluation in patients with inadequately controlled type 1 diabetes) trials demonstrated significant benefits in adult patients with T1D. The SGLT inhibitors may become the first oral medication to be approved for adjunctive use in T1D. SUMMARY: The risk of diabetic ketoacidosis still remains a concern, but considering additional benefits beyond glucose control, with proper counseling and education, these medications may allow a larger number of patients to achieve target glucose control without weight gain or increased risk of hypoglycemia. PMID- 29794498 TI - Bone health in type 1 diabetes. AB - PURPOSE OF REVIEW: This article reviews recent publications on the effect of type 1 diabetes (T1D) on fracture risk, bone mineral density (BMD), bone structure, and bone tissue quality. Possible fracture prevention strategies for patients with T1D have also been reviewed. RECENT FINDINGS: T1D is associated with substantially elevated fracture risk and modestly low BMD at the femoral neck. However, BMD alone does not explain higher observed fracture risk in T1D. T1D also affects bone macro- and microstructure, characterized by thinner cortices and trabecular bone changes such as thinner and more widely spaced trabeculae. Structural bone deficit is pronounced in the presence of microvascular complications. Tissue-level changes, such as accumulation of advanced glycation endproducts, detrimental alterations of the mineral phase because of low bone turnover, and occlusion of vascular channels in bone by mineralized tissue, are implicated in pathophysiology of bone fragility in T1D. There are no guidelines on screening and prevention of osteoporotic fractures in T1D. SUMMARY: More studies are needed to understand the influence of T1D on structural bone quality and tissue material properties. There is a need for a prospective study to evaluate better screening strategies for diagnosis and treatment of osteoporosis in T1D. PMID- 29794499 TI - Efficacy and Safety of Oral NEPA (Netupitant/Palonosetron), the First Fixed Combination Antiemetic, in Patients With Gynecological Cancers Receiving Platinum Based Chemotherapy. AB - OBJECTIVE: Patients with gynecological cancers are at high risk for chemotherapy induced nausea and vomiting (CINV) after platinum-based chemotherapy (CT). NEPA (300-mg netupitant, 0.50-mg palonosetron) is the first oral fixed-combination antiemetic. Pivotal trials demonstrated the superiority of oral NEPA over intravenous palonosetron in preventing CINV after highly emetogenic (anthracycline-cyclophosphamide-based [AC] and cisplatin-based [non-AC]) CT. This post hoc subset analysis considered patients with gynecological cancer receiving cisplatin- or carboplatin-based CT from 1 pivotal trial and from 1 multicycle safety trial to evaluate the efficacy of oral NEPA in preventing CINV. METHODS: Single-dose NEPA was given before CT in combination with dexamethasone. The efficacy end points for the acute (0-24 hours), delayed (25-120 hours), and overall (0-120 hours) CINV phases after CT included complete response (CR; no emesis, no rescue medication) and no significant nausea (<25 mm on a 0- to 100-mm visual analog scale). Safety was also assessed. RESULTS: For cisplatin-induced CINV, NEPA achieved high CR rates (acute phase: >90%; delayed, overall phases: >=85%). For carboplatin-induced CINV, NEPA was also highly effective, with high acute, delayed, and overall CR rates (cycle 1: >75%; cycles 2-4: >95%). No significant nausea rates were more than 90% and more than 80% in the acute and delayed phases, respectively, for patients receiving cisplatin or carboplatin. NEPA was well tolerated. CONCLUSIONS: Results suggest that oral NEPA is effective and safe in preventing CINV in patients with gynecological cancers treated with cisplatin- or carboplatin-based CT. Single fixed-combination NEPA is a convenient option for CINV prevention in high-risk CINV patients. PMID- 29794500 TI - Predictors of Locally Advanced Disease at Presentation and Clinical Outcomes Among Cervical Cancer Patients Admitted at a Tertiary Hospital in Botswana. AB - OBJECTIVES: The aim of this study was to determine predictors of locally advanced disease at presentation and clinical outcomes among cervical cancer patients in Botswana to inform interventional strategies. METHODS: Retrospective review of 149 medical records of new cervical cancer patients was conducted between August 2016 and February 2017 at the Princess Marina Hospital. Data collected included sociodemographics, presenting symptoms, stage of disease, comorbidities, interventions, and clinical outcomes. STATA 12 was used for data analysis. Frequencies were used to describe patient demographics and clinical variables. Bivariate and multivariate binary logistic regression analyses were used to determine association between stage of disease at presentation and patient characteristics. P <= 0.05 was considered significant. RESULTS: Mean age was 49.5 years. Nine (89.2%) in 10 patients had locally advanced cervical cancer (stage IB1-IVB). Two thirds (65.1%) were human immunodeficiency virus positive. Previous cervical cancer screening was low at 38.3%. Common symptoms were abnormal vaginal bleeding, low abdominal pain, and malodorous vaginal discharge reported among 75.8%, 66.4%, and 39.6% of cases, respectively. Overall, 32 (21.5%) were declared cured, 52 (34.9%) improved, and 11 (7.4%) opted for home-based care. Hospital deaths were 41 (27.5%). Major causes of death were renal failure (48.7%) and severe anemia (39%). Thirteen (8.7%) were lost to follow-up. Being unmarried (odds ratio [OR], 3.9), lack of cervical cancer screening (OR, 6.68), presentation with vaginal bleeding (OR, 7.69), and low abdominal pain (OR, 4.69) were associated with advanced disease at presentation. CONCLUSIONS: Lack of cervical cancer screening, vaginal bleeding, low abdominal pain, and unmarried status were associated with advanced disease at presentation. We recommend scale up of cervical cancer screening and its integration into routine human immunodeficiency virus care. Capacity building in gynecologic oncology and palliative care services is currently critical. PMID- 29794502 TI - Commentary Regarding "A Cyst Compressing the Ulnar Nerve Motor Branch. Ultrasonographic Diagnosis of a Tricking Neuropathy". PMID- 29794501 TI - Three-dimensional Analysis of How Radiation Affects Deep Inferior Epigastric Perforator (DIEP) Flap Volume, Projection, and Position in Breast Cancer Reconstruction. AB - BACKGROUND: The deep inferior epigastric perforator (DIEP) flap has gained popularity for autologous free flap breast reconstruction. Historically, patients receiving post mastectomy radiation therapy (PMRT) were not candidates for immediate autologous reconstruction due to concerns for flap volume depletion, fat necrosis, and flap failure. However, this literature is anecdotal and lacks case controls. We objectively analyzed the effects radiation imparts on immediate DIEP flap reconstruction using 3-dimensional software and inherent controls. METHODS: We performed a cohort study on breast cancer patients who underwent immediate bilateral DIEP flap reconstructions followed by PMRT between 2005 and 2014. Exclusion criteria included patients less than 6 months from PMRT completion and bilateral PMRT. Three-dimensional photographs were analyzed using Geomagic (Rock Hill, SC) software to compare flap position, projection, and volume between the irradiated and nonirradiated reconstructed breasts. Breast Q survey evaluated patients' satisfaction. RESULTS: Eleven patients met inclusion criteria. Average time from PMRT completion to photo acquisition was 1.93 years. There was no statistical difference in average volume or projection in the irradiated versus nonirradiated side (P = 0.087 and P = 0.176, respectively). However, position of the irradiated flaps was significantly higher on the chest wall compared to controls (mean difference, 1.325 cm; P < 0.004). CONCLUSIONS: Three-dimensional analysis exhibited no statistical differences in projection or volume between irradiated DIEP flaps and nonirradiated controls. However, irradiated DIEP flaps were positioned higher on the chest wall, similar to observations in irradiated tissue expanders/implants. Patients were satisfied as measured by Breast Q. Immediate bilateral DIEP flap reconstructions can safely be performed with PMRT with satisfactory results. PMID- 29794503 TI - A Comparative Clinical Study of Flap Thickness: Medial Sural Artery Perforator Flap Versus Anterolateral Thigh Flap. AB - INTRODUCTION: The purpose of this study is to measure flap thicknesses of anterolateral thigh (ALT) and medial sural artery perforator (MSAP) flaps in healthy subjects by Doppler ultrasonography and compare the results in relation to sex and body mass index (BMI). METHOD: The perforators of ALT and MSAP flaps were marked on 30 healthy subjects. The thickness of skin and subcutaneous tissue was measured in millimeters at the site of the perforator using Doppler ultrasonography. RESULTS: The mean +/- SD age of the participants was 36.4 +/- 10.5, the mean +/- SD BMI was 25.2 +/- 3.9 (19.4-32.5). The mean +/- SD flap thickness was 11.55 +/- 4.38 mm for ALT and 8.31 +/- 3.6 mm mm for MSAP (P < 0.01). Anterolateral thigh flap was significantly thicker than MSAP in both males (9.02 vs 6.11 mm) and females (14.07 vs 10.52 mm) (P < 0.05). The thickness of both MSAP and ALT flap had a positive correlation with BMI. The relationship was stronger for ALT in males (r = 0.66 for ALT, r = 0.59 for MSAP) and for MSAP in females (r = 0.70 for ALT, r = 0.83 for MSAP). DISCUSSION: This study confirms that MSAP flap is thinner than ALT and the results correlate with BMI. Therefore, MSAP flap can be considered a good alternative to ALT, to avoid bulk, in reconstruction of shallower soft tissue defects. PMID- 29794504 TI - Chest Wall-Based Flap for Repairing Partial Mastectomy Defects: A Multipurpose Flap. AB - OBJECTIVE: The objective of this study is to introduce a single and reproducible tissue-rearrangement oncoplastic technique that is applicable for all quadrants partial-mastectomy defects in small- to medium-sized breasts, using grounds drawn from cosmetic surgery. METHODS: Eleven small- to medium-sized breast cancer patients with tumor involvement of more than a quarter of the breast were operated on using the chest wall-based flap technique. The procedure is described in detail, and the results are analyzed in terms of both cosmetic and oncological results. RESULTS: The flap successfully reached all breast quadrants as necessary, as well as the areola-nipple complex. The resection borders were found to be free of tumor in all cases, and there were no perioperative complications. Patients rated nearly all the cosmetic parameters as "somewhat satisfied" or "very satisfied," and there was no evidence of fat necrosis in the postoperative mammography examinations. CONCLUSIONS: Applying principles taken from the cosmetic plastic surgery lies at the base of any high standard reconstructive surgery in general and oncoplastic breast surgery in particular. The chest wall based flap is suitable for the reconstruction of a wide range of breast lumpectomy defects and is feasible for small- to medium-sized breasts, which are usually not easily amenable to tissue rearrangement techniques. The learning curve is short, with replicable results. PMID- 29794505 TI - Use of a Vertical Muscle-Sparing Latissimus Dorsi Flap in Implant-Based Breast Reconstruction Without Position Change. AB - BACKGROUND: The use of various latissimus dorsi (LD) flap types in combination with implants is a safe and reliable 1-stage breast reconstruction method. However, 1 or more positional changes are generally required during the procedure. We designed a vertical skin paddle that was centered along the midaxillary line and harvested the required LD muscle amount based on the thoracodorsal artery descending branch, thereby completing flap elevation, inset, and donor-site closure in the supine position following skin-sparing mastectomy. METHODS: Between July 2017 and September 2017, we enrolled patients who underwent breast reconstruction using the vertical muscle-sparing LD (ms-LD) flap with an implant. The vertical ms-LD flap was selected when the nipple-areolar complex could not be spared or when adjuvant radiation therapy was anticipated. RESULTS: Eleven patients were enrolled in the study. All patients underwent skin-sparing mastectomy (with excision of the nipple-areolar complex for oncological reason). The mean mastectomy specimen weight was 402.3 g. The average flap length and width were 15.2 and 5.5 cm, respectively. The mean implant size was 290 mL. The average operative time was 112 minutes. All surgical procedures were performed in the supine position, and the flap reached the most medial part of the breast without any tension in all cases. The mean follow-up length was 87 days, and no complications such as infection, partial flap loss, or donor-site seroma were observed. CONCLUSIONS: Vertical ms-LD flaps can be harvested and utilized in direct-to-implant reconstructions when a skin paddle (or banking) is required, or when acellular dermal matrix use is precluded, or when additional soft tissue coverage is mandatory in high-risk patients not requiring intraoperative position changes. This technique can shorten the operation time and may reduce donor-site morbidity and associated complications. PMID- 29794506 TI - Merkel Cell Carcinoma of the Wrist: A Case Report. AB - PURPOSE: Merkel cell carcinomas are a rare type of neuroendocrine tumors of the head, neck, and extremities commonly found in older patients. Merkel cell carcinomas present as red-to-purple and nontender nodules with or without surface ulceration, usually measuring 2 cm in diameter. CASE PRESENTATIONS: An 83-year old woman with a skin-colored nodule on the dorsal aspect of her right wrist was referred to our department for treatment. The regional lymph nodes were not palpable, and the positron emission tomography/computed tomography scan did not reveal any distant metastases. We conducted wide excision of the lesion and sentinel lymph node biopsy. The defect caused by the excision and partial bone resection was reconstructed using a radical forearm rotational flap and a split thickness skin graft. Postoperatively, the patient received adjuvant radiation therapy. We observed wound healing and an absence of complications such as recurrence at 1-year follow-up. CONCLUSIONS: Merkel cell carcinomas are rare but aggressive neuroendocrine skin cancers, which rarely occur in the upper extremity. Our treatment of nonamputative wide excision and sentinel lymph node dissection, followed by postoperative radiation therapy, showed no local or distant recurrence. Here, we review the current literature on Merkel cell carcinomas and describe our approach of treatment. PMID- 29794507 TI - Medial Plantar Venous Flap: Classic Donor Site Modification for Hand Defects. AB - BACKGROUND: Destruction of digits from trauma results in a much more significant influence on patients' mental state and quality of life than do injuries to other parts. The purpose of this study was to describe a novel modification of medial plantar venous flap for soft tissue defects in the hands and digits. METHODS: Nine patients received medial plantar venous flap to resurface soft tissue defects in the hands or digits between January 2015 and February 2017. This flap can be used either in a free-island pattern or in a flow-through pattern through the medial branch of the great saphenous vein. All patient data including preoperative statues and follow-up examinations (flap survival rates, complication rates, total active motion, static 2-point discrimination, and Semme Weinstein test score) were analyzed. RESULTS: We included 6 men and 3 women, with a mean age of 34.2 years. The medial plantar venous flaps were used for vascularization in 5 patients because of segmental defects of bilateral digit arteries. Eight flaps survived uneventfully in this study. One flap partially failed (20% of the flap area) because of venous congestion. The functional outcomes and sensory restoration were satisfied for all 9 flaps. CONCLUSIONS: Compared with the traditional medial plantar flap, the medial plantar venous flap involves a simpler surgical procedure and allows for revascularization of distal areas using the flow-through technique. Furthermore, the medial plantar area presents a sensitive, glabrous skin with proper bulkiness and allows for movement of the underlying structure. PMID- 29794508 TI - Three-dimensional Photogrammetric Analysis of Facial Soft-to-Hard Tissue Ratios After Bimaxillary Surgery in Facial Asymmetry Patients With and Without Sturge Weber Syndrome. AB - Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome characterized by facial port-wine stains. Most patients with facial asymmetry due to SWS have soft and/or hard tissue hypertrophy and require both soft tissue correction and bone surgery. In our experience, because SWS patients are more likely than non-SWS patients to be dissatisfied after bone surgery because of limited soft tissue change, we compared soft tissue changes after bimaxillary surgery between facial asymmetry patients with and without SWS.All patients-5 with SWS and 5 without SWS underwent bimaxillary surgery by a single surgeon. Soft-to-hard ratios were determined using the preoperative and postoperative vertical lengths from the intersection point between the external orbital contour laterally and the oblique orbital line (LO) to the occlusion line (OL) and the LO to the mandible angle (AG) on cephalography and the distances between the lateral canthus (LC) and oral commissure (OC) and between the LC and soft tissue gonion (Go') on 3-dimensional scanned images.The average change in the [LC-OC] to [LO-OL] ratio was 23.03% +/- 10.09% in SWS patients and 88.05% +/- 10.44% in non-SWS patients (P = 0.008). The average change in the [LC-Go'] to [LO-AG] ratio was 35.54% +/- 15.47% in SWS patients and 78.90% +/- 47.56% in non-SWS patients (P = 0.032).Soft-to-hard tissue ratios after orthognathic surgery are significantly smaller in SWS patients than in non-SWS patients. This information is important for preoperative patient counseling, managing patient expectations, enhancing results, and planning the second-stage soft tissue surgery. PMID- 29794509 TI - Availability and Safety of Osteotomy in Esthetic Rhinoplasty of East Asian Patients. AB - OBJECTIVE: East Asians usually have short and flat noses and broad nasal bones. Therefore, rhinoplasty with dorsal augmentation and nasal osteotomy is often required. However, many surgeons are wary of performing nasal osteotomy in conjunction with augmentation with silicone. The authors sought to evaluate the availability and safety of osteotomy in esthetic rhinoplasty of East Asian patients. METHODS: In a clinical study, a retrospective chart review was performed for 227 patients who had undergone nasal osteotomy (paramedian oblique osteotomy plus percutaneous lateral osteotomy) and dorsal augmentation with silicone. Patient satisfaction after surgery was evaluated by the Rhinoplasty Outcome Evaluation test. In addition, a cadaveric study was conducted in which 5 fresh cadavers received different osteotomies on each side of the nose (right side: paramedian oblique and percutaneous lateral osteotomy; left side: medial oblique and intranasal continuous lateral osteotomy). RESULTS: In the clinical study, patients were satisfied with the outcome after esthetic rhinoplasty with nasal osteotomy (paramedian oblique osteotomy plus percutaneous lateral osteotomy) and augmentation with silicone. The results revealed a low complication rate. The average Rhinoplasty Outcome Evaluation test score significantly increased (P < 0.001), with 91.2% of patients scoring their postoperative result better than "good." In the cadaveric study, stability was greater when paramedian oblique and percutaneous lateral osteotomy was performed. CONCLUSIONS: Paramedian oblique and percutaneous lateral osteotomy is effective for reducing broad nasal bones, thus providing a stable framework and a reliable method for achieving a good outcome when augmentation with silicone is performed simultaneously. PMID- 29794510 TI - An Evaluation of Reporting Guidelines and Clinical Trial Registry Requirements Among Plastic Surgery Journals. AB - BACKGROUND: Ensuring that published studies are of the highest methodological quality is a critical step in plastic surgery's transition to a more evidence based field. Reporting guidelines and reporting of clinical trial registration may serve as promising avenues of increasing the methodological quality in plastic surgery trials. OBJECTIVE: The objective of this study is to evaluate the rate at which plastic surgery journals require reporting guidelines, as well as the effect these policies have on adherence to reporting guidelines. METHODS: Using journal's "Instructions for Authors," we conducted a cross-sectional survey to evaluate journal policies regarding adherence to reporting guidelines and trial registration. We also examined whether trials published in journals referencing Consolidated Standards of Reporting of Trials (CONSORT) had higher rates of compliance with publishing a CONSORT flow diagram and whether journals with trial registration policies were more likely to contain registered trials than journals without these requirements. RESULTS: Of the 20 plastic surgery journals, 13 (65%) did not mention a single guideline within their instructions to authors. Furthermore, 10 (50%) did not mention policies regarding clinical trial registration. In addition, journals with policies regarding the CONSORT statement were more likely to publish trials with a CONSORT flow diagram, and journals with policies regarding clinical trial registry were more likely to publish trials reporting registration. CONCLUSION AND RELEVANCE: Our study found that few plastic surgery journals mention reporting guidelines or trial registration in their instructions for authors. Our study also found that journal policies regarding guideline adherence and trial registration seem to be effective mechanisms toward improvement, and plastic surgery journals should consider adopting such policies. PMID- 29794511 TI - Value of Free-text Comments for Validating Cancer Cases Using Primary-care Data in the United Kingdom. PMID- 29794513 TI - Bone Lesions of Sarcoidosis. PMID- 29794512 TI - Erratum for "Biases in Randomized Trials: A Conversation Between Trialists and Epidemiologists." PMID- 29794515 TI - Adult-Onset Still Disease Presenting With Insterstitial Lung Disease and Dermatomyositis-Like Atypical Persistent Eruption Successfully Treated With Mycophenolate Mofetil. PMID- 29794514 TI - Coffee and Tea Consumption in Relation to Risk of Rheumatoid Arthritis in the Women's Health Initiative Observational Cohort. AB - OBJECTIVE: The aim of this study was to evaluate whether tea or coffee consumption is associated with an increased risk of older-onset rheumatoid arthritis (RA) using the Women's Health Initiative Observational Study. METHODS: The Women's Health Initiative Observational Study is a longitudinal prospective cohort study conducted from 1993 to 1998. There were 76,853 women who completed a self-administered questionnaire about their daily consumption of tea and coffee. One hundred eighty-five women self-reported and validated incident cases of RA were observed after 3 years of observation. Multivariable Cox proportional hazards models were performed to assess the relationship between consumption habits and disease incidence. Trend tests were calculated using categorical variables modeled as a continuous variable without collapsing. RESULTS: There was no increase in the hazard ratio for incident RA in those participants who drank coffee compared with those who did not. The amount of coffee consumed and the method of preparation (caffeinated/decaffeinated; filtered/unfiltered) also did not alter the risk of incident RA. There was a positive association of incident RA and caffeinated tea consumption in the trend test (P = 0.03). When assessing any caffeinated tea consumption versus no tea consumption, the hazard ratio for incident RA was 1.40 (confidence interval, 1.01-1.93; P = 0.04). CONCLUSIONS: In a large prospective cohort of older women, there was no association between coffee consumption and incident RA. A small association between daily caffeinated, nonherbal tea consumption and incident RA was found. PMID- 29794516 TI - Atraumatic Incomplete Sternal Fracture Incidentally Detected in a Human Immunodeficiency Virus Patient at Lung Cancer Screening With Low-Dose Thoracic CT. PMID- 29794517 TI - Measuring Mindsets and Achievement Goal Motivation: A Validation Study of Three Instruments. AB - PURPOSE: To evaluate the validity of scores from three instruments measuring achievement goal motivation-related constructs: a shortened version of Dweck's Implicit Theories of Intelligence Scale (ITIS-S), measuring incremental and entity mindsets; Elliot's Achievement Goal Questionnaire-Revised (AGQ-R), measuring mastery-approach, mastery-avoidance, performance-approach, and performance-avoidance achievement goals; and Midgley's Patterns of Adaptive Learning Scales (PALS), measuring mastery, performance-approach, and performance avoidance achievement goals. METHOD: High school students participating in a medical simulation training activity in May 2017 completed each instrument. The authors evaluated internal structure using reliability and factor analysis and relations with other variables using the multitrait-multimethod matrix. RESULTS: There were 178 participants. Internal consistency reliability (Cronbach alpha) was > 0.70 for all subscores. Confirmatory factor analysis of ITIS-S scores demonstrated good model fit. Confirmatory factor analysis of AGQ-R scores demonstrated borderline fit; exploratory factor analysis suggested a three-domain model (approach, mastery-avoidance, performance-avoidance). Confirmatory factor analysis of PALS scores also demonstrated borderline fit; exploratory factor analyses suggested consistent distinction between mastery and performance goals but inconsistent distinction between performance-approach and performance avoidance goals. Correlations among AGQ-R and PALS scores were large for mastery (r = 0.72) and moderate for performance (>= 0.45) domains; correlations among incremental and mastery scores were moderate (>= 0.34). Contrary to expectations, correlations between entity and performance scores were negligible. Correlations between conceptually unrelated domains were small or negligible. CONCLUSIONS: All instrument scores had good internal consistency and generally appropriate relations with other variables, but empirically determined domain structures did not consistently match theory. PMID- 29794518 TI - Leveraging the Continuum: A Novel Approach to Meeting Quality Improvement and Patient Safety Competency Requirements Across a Large Department of Medicine. AB - PROBLEM: Quality improvement (QI) and patient safety (PS) are now core competencies across the medical education continuum. A major challenge to developing and implementing these new curricular requirements is the lack of faculty expertise. APPROACH: In 2015, the authors developed a centralized, vertically integrated, competency-based approach to meet QI/PS educational requirements across the continuum of graduate medical education in the Department of Medicine, Perelman School of Medicine, University of Pennsylvania. By leveraging the QI/PS expertise of one individual, the authors identified and trained core QI/PS faculty members and sequentially deployed QI/PS activities that were tailored to the learner level and specialty. The curriculum includes PS event reporting, systems thinking and root causes analysis skills, adverse event disclosure, and a QI workshop series and project. OUTCOMES: PS event reporting, an indication of engagement in PS culture, increased by 186% among interns, 384% among postgraduate year 2 and 3 residents, and 613% among fellows between academic years (AYs) 2013-2014 and 2016-2017. In AY 2017-2018, 9 faculty members and 40 fellows from 9 fellowships participated in the QI workshop series, and 53 fellows from 7 fellowships participated in the adverse event disclosure simulation activity. All educational activities were rated highly. NEXT STEPS: The authors are expanding the adverse event disclosure activity to include residents and the remaining fellowship programs, identifying fellowships to pilot curricular efforts related to clinical quality metrics, developing introductory activities in basic QI/PS concepts for medical students, and evaluating the impact of efforts on participating faculty members. PMID- 29794519 TI - Shifting and Sharing: Academic Physicians' Strategies for Navigating Underperformance and Failure. AB - PURPOSE: Medical practice is uncertain and complex. Consequently, even outstanding performers will inevitably experience moments of underperformance and failure. Coping relies on insight and resilience. However, how physicians develop and use these skills to navigate struggle remains underexplored. A better understanding may reveal strategies to support both struggling learners and stressed practitioners. METHOD: In 2015, 28 academic physicians were interviewed about their experiences with underperformance or failure. Constructivist grounded theory informed data collection and analysis. RESULTS: Participants' experiences with struggle ranged from patient errors and academic failures to frequent, smaller moments of interpersonal conflict and work-life imbalance. To buffer impact, participants sometimes shifted their focus to an aspect of their identity where they felt successful. Additionally, although participants perceived that insight develops by acknowledging and reflecting on error, they sometimes deflected blame for performance gaps. More often, participants seemed to accept personal responsibility while simultaneously sharing accountability for underperformance or failure with external forces. Paradoxically, participants perceived learners who used these strategies as lacking in insight. CONCLUSIONS: Participants demonstrated the protective and functional value of distributing responsibility for underperformance and failure. Shifting and sharing may be an element of reflection and resilience; recognizing external factors may provide a way to gain perspective and to preserve the self. However, this strategy challenges educators' assumptions that learners who deflect are avoiding personal responsibility. The authors' findings raise questions about what it means to be resilient, and how assumptions about learners' responses to failure may affect strategies to support underperforming learners. PMID- 29794520 TI - Changes in Teaching Hospitals' Community Benefit Spending After Implementation of the Affordable Care Act. AB - PURPOSE: U.S. teaching hospitals that qualify as 501(c)(3) organizations (a not for-profit designation) are required to demonstrate community benefit annually. Increases in health insurance access driven by Affordable Care Act (ACA) implementation, along with new regulations, research opportunities, and educational expectations, may be changing hospitals' allocations of community benefit dollars. This study aimed to describe changes in teaching hospitals' community benefit spending between 2012 (pre-ACA implementation) and 2015 (post ACA implementation), and to explore differences in spending changes between hospitals in Medicaid expansion and nonexpansion states. METHOD: In 2017, for each teaching hospital member of the Association of American Medical Colleges' (AAMC's) Council of Teaching Hospitals and Health Systems required to submit Form 990s to the Internal Revenue Service, the authors sought community benefit spending data for 2012 and 2015 as reported on Schedule H. RESULTS: The analysis included 169 pairs of Form 990s representing 184 AAMC member teaching hospitals (93% of 198 eligible hospitals). Compared with 2012, hospitals in 2015 spent $3.1 billion (20.14%) more on community benefit despite spending $804 million (16.17%) less on charity care. Hospitals in Medicaid expansion states increased spending on subsidized health services and Medicaid shortfalls at rates higher than hospitals in nonexpansion states. The latter increased spending at higher rates on community health improvement and cash/in-kind contributions. CONCLUSIONS: After ACA implementation, teaching hospitals increased their overall community benefit spending while their charity care spending declined. Changes in community benefit spending differed according to states' Medicaid expansion status, demonstrating hospitals' responsiveness to state and local realities. PMID- 29794521 TI - Academic Health Centers and Medicaid: Advance or Retreat? AB - The expansion of Medicaid under the Affordable Care Act has strained the capacity of many academic health centers (AHCs) to deliver primary and specialty care to this traditionally underserved population. The authors, longtime faculty members in the University of California, Davis Health (UCDH) system, discuss the challenges of UCDH's participation in Medi-Cal, the nation's largest Medicaid program, and their institution's controversial decision in 2015 to withdraw from its last Medi-Cal primary care contract, which has had untoward effects on UCDH's social and educational missions. The authors call on AHCs to leverage their considerable intellectual and human capital as well as their focus on education and research to aggressively pursue innovative models of high-value primary care for underserved populations in their local communities, highlighting several recent successful examples of such programs. The UCDH experience has implications for other AHCs grappling with the financial realities of an increasingly competitive, value-based health care marketplace and the inherent difficulty in balancing educational, research, patient care, and social or community service missions. PMID- 29794522 TI - Medicaid Innovations and the Role of Academic Health Centers. AB - Although they represent less than 8% of all U.S. hospitals, academic health centers (AHCs) deliver almost 40% of the inpatient care for Medicaid beneficiaries. However, because of low Medicaid reimbursement rates, AHCs have had to rely on supplemental funding sources, such as disproportionate share hospital (DSH) payments and upper payment limit (UPL) payments. Recent legislative efforts and changes to payment structures have made these sources vulnerable to severe reductions. For instance, DSH payments are scheduled to be cut by $8 billion by 2021, and UPL payments are a diminishing resource for many states because the program is based on a fee-for-service model and most states are moving to managed care.In this Invited Commentary, the authors argue that cuts to supplemental funding sources would harm AHCs. They advocate instead for restructuring traditional supplemental payments to accommodate novel reimbursement models. They cite Medicaid's Delivery System Reform Incentive Payment program as an example of work to leverage supplemental payments to transform the delivery of care for Medicaid beneficiaries. AHCs should be at the epicenter of such innovations in population health for Medicaid beneficiaries. To that end, the authors encourage AHCs to build new partnerships with community based primary care physicians and community health centers to balance the specialty composition of their faculty providers to assume the risk for Medicaid beneficiaries and other vulnerable populations. PMID- 29794523 TI - Asking for Less and Getting More: The Impact of Broadening a Rater's Focus in Formative Assessment. AB - PURPOSE: There may be unintended consequences of broadening the competencies across which health professions trainees are assessed. This study was conducted to determine whether such broadening influences the formative guidance assessors provide to trainees and to test whether sequential collection of competency specific assessment can overcome setbacks of simultaneous collection. METHOD: A randomized between-subjects experimental design, conducted in Toronto and Halifax, Canada, in 2016-2017 with paramedic educators experienced in observing/rating, in which observers' focus was manipulated. In the simultaneous condition, participants rated four unscripted (i.e., spontaneously generated) clinical performances using a six-dimension global rating scale and provided feedback. In three sequential conditions, participants were asked to rate the same performances and provide feedback but for only two of the six dimensions. Participants from these conditions were randomly merged to create a "full score" and set of feedback statements for each candidate. RESULTS: Eighty-seven raters completed the study; 23 in the simultaneous condition and 21 or 22 for each pair of dimensions in the sequential conditions. After randomly merging participants, there were 21 "full scores" in the sequential condition. Compared with the sequential condition, participants in the simultaneous condition demonstrated reductions in the amount of unique feedback provided, increased likelihood of ignoring some dimensions of performance, lessened variety of feedback, and reduced reliability. CONCLUSIONS: Sequential or distributed assessment strategies in which raters are asked to focus on less may provide more effective assessment by overcoming the unintended consequences of asking raters to spread their attention thinly over many dimensions of competence. PMID- 29794524 TI - Faculty Development Revisited: A Systems-Based View of Stakeholder Development to Meet the Demands of Entrustable Professional Activity Implementation. AB - In 2015, the Association of American Medical Colleges implemented an interinstitutional pilot of 13 core entrustable professional activities (EPAs) for entering residency, activities that entering residents should be expected to perform with indirect supervision. The pilot included a concept group on faculty development; this group previously offered a shared mental model focused on the development of faculty who devote their efforts to clinical teaching and assessment for learning and entrustment decision making. In this article, the authors draw from the literature of competency-based education to propose what is needed in overall approaches to faculty development to prepare institutions for undergraduate EPA implementation.Taking a systems-based view that defines the necessary tasks of EPA implementation, the authors move beyond the variably used term "faculty" and enumerate a comprehensive list of institutional stakeholders who can meaningfully support and/or engage in the relationships and organizational processes required for EPA learning and assessment. They consider each group's responsibilities and development needs according to five domains delineated by Steinert: teaching improvement, leadership and management, research building capacity, academic career building, and organizational change.The authors argue that the EPA framework addresses barriers posed with the use of a competency-based framework. By facilitating the communication required for organizational change, enabling valid assessment with comprehensive yet feasible levels of faculty development, and incorporating all relevant data on student professional behavior into summative assessment decisions, EPAs may offer a clearer path toward the goal of competency-based education. PMID- 29794525 TI - A Conceptual Model for Understanding Academic Physicians' Performances of Identity: Findings From the University of Utah. AB - PURPOSE: To explore how academic physicians perform social and professional identities and how their personal experiences inform professional identity formation. METHOD: Semistructured interviews and observations were conducted with 25 academic physicians of diverse gender and racial/ethnic backgrounds at the University of Utah School of Medicine from 2015 to 2016. Interviews explored the domains of social identity, professional identity, and relationships with patients and colleagues. Patient interactions were observed. Interviews and observations were audio-recorded, transcribed, and analyzed using grounded theory. RESULTS: Three major themes emerged: Physicians' descriptions of identity differed based on social identities, as women and racially/ethnically minoritized participants linked their gender and racial/ethnic identities, respectively, to their professional roles more than men and white, non-Latino/a participants; physicians' descriptions of professional practice differed based on social identities, as participants who associated professional practices with personal experiences often drew from events connected to their minoritized identities; and physicians' interactions with patients corresponded to their self-described actions. CONCLUSIONS: Professional identity formation is an ongoing process, and the negotiation of personal experiences is integral to this process. This negotiation may be more complex for physicians with minoritized identities. Implications for medical education include providing students, trainees, and practicing physicians with intentional opportunities for reflection and instruction on connecting personal experiences and professional practice. PMID- 29794526 TI - Value-Added Activities in Medical Education: A Multisite Survey of First- and Second-Year Medical Students' Perceptions and Factors Influencing Their Potential Engagement. AB - PURPOSE: To describe attitudes of first- and second-year U.S. medical students toward value-added medical education, assess their self-reported desire to participate in value-added activities, and identify potentially modifiable factors influencing their engagement. METHOD: The authors conducted a cross sectional survey of first- and second-year students at nine U.S. medical schools in 2017. Survey items measured students' attitudes toward value-added medical education (n = 7), desire to participate in value-added activities (n = 20), and factors influencing potential engagement (n = 18). RESULTS: Of 2,670 students invited to participate, 1,372 (51%) responded. Seventy-six percent (1,043/1,368) moderately or strongly agreed they should make meaningful contributions to patient care. Students' desire to participate was highest for patient care activities approximating those traditionally performed by physicians, followed by systems improvement activities and lowest for activities not typically performed by physicians. Factors increasing desire to participate included opportunities to interact with practicing physicians (1,182/1,244; 95%), patients (1,177/1,246; 95%), and residents or fellows (1,166/1,246; 94%). Factors decreasing desire to participate included making changes to the health care system (365/1,227; 30%), interacting with patients via phone or electronic communication (410/1,243; 33%), and lack of curricular time (634/1,233; 51%). CONCLUSIONS: First- and second-year medical students agree they should add value to patient care, but their desire to participate in value-added activities varies depending on the nature of the tasks. Medical schools may be able to increase students' desire to participate by enabling face-to-face interactions with patients, embedding students in health care teams, and providing dedicated curricular time. PMID- 29794527 TI - "Being on Both Sides": Canadian Medical Students' Experiences With Disability, the Hidden Curriculum, and Professional Identity Construction. AB - PURPOSE: Medical students with disabilities hold firsthand knowledge as health care recipients, yet face barriers to disclosure and support. Their experiences provide a unique lens for understanding professional identity construction; this study explored how disabled medical students experience training as both patients and trainees. METHOD: The authors conducted qualitative interviews with 10 medical students at the University of Toronto Faculty of Medicine with self identified disabilities. They performed textual analysis of documents concerning medical student wellness from 13 Canadian universities, including policies, student services, and student blogs (July 2016 to March 2017). Using principles of critical discourse analysis, the authors coded the interviews and texts to identify operating discourses and core themes, drawing from sociocultural theories of professional identity construction and the hidden curriculum. RESULTS: Two dominant discourses emerged from the interviews and texts, revealing institutionalized notions of the perceived "good student" and "good patient." These roles held contradictory demands, demonstrating how institutions often implicitly and explicitly framed wellness as a means to optimal academic performance. Two additional themes, "identity compartmentalization" and "identity intersection," captured students' experiences navigating identities as patients and trainees. Although students lacked explicit opportunities to express their expertise as patients in the formal curriculum, their experiences in both roles led to improved communication, advocacy, and compassion. CONCLUSIONS: Institutional discourses around disability and academic performance hold material implications for curricular content, clinical teaching, and availability of supports in medical school. By repositioning students' experiences with disability as sources of expertise, this study highlights opportunities for teaching compassionate care. PMID- 29794528 TI - Sexual Harassment in Medical Schools: The Challenge of Covert Retaliation as a Barrier to Reporting. AB - Although Title IX, the federal law prohibiting sexual harassment in educational institutions, was enacted in 1972, sexual harassment continues to be distressingly common in medical training. In addition, many women who experience sexual harassment do not report their experiences to authorities within the medical school.In this article, the authors review the literature on the prevalence of sexual harassment in medical schools since Title IX was enacted and on the cultural and legal changes that have occurred during that period that have affected behaviors. These changes include decreased tolerance for harassing behavior; increased legal responsibility assigned to institutions; and a significant increase in the number of female medical students, residents, and faculty. The authors then discuss persisting barriers to reporting sexual harassment, including fears of reprisals and retaliation, especially covert retaliation. They define covert retaliation as vindictive comments made by a person accused of sexual harassment about his or her accuser in a confidential setting, such as a grant review, award selection, or search committee.The authors conclude by highlighting institutional and organizational approaches to decreasing sexual harassment and overt retaliation, and they propose other approaches to decreasing covert retaliation. These initiatives include encouraging senior faculty members to intervene and file bystander complaints when they witness inappropriate comments or behaviors as well as group reporting when multiple women are harassed by the same person. PMID- 29794529 TI - Functional Outcome of Elderly Hip Fracture Patients Is Not Affected By Prefracture Dementia. AB - OBJECTIVE: The aim of the study was to examine whether a diagnosis of prefracture dementia (PFD) affects functional outcome at discharge from a geriatric rehabilitation setting. DESIGN: A total of 211 consecutive elderly hip fracture patients were evaluated retrospectively. We used the Functional Independence Measure (FIM) and analyzed data by t test, chi test, and multiple linear regression analysis. RESULTS: Patients with PFD were older (P = 0.001), presented with lower Mini-Mental State Examination scores (P < 0.001) and lower prefracture function (P < 0.001). Total-FIM and motor-FIM scores at admission and discharge, as well as FIM gain scores at discharge, were lower among patients with PFD, compared with nonprefracture dementia (NPFD) patients (P < 0.001). The FIM daily gains (efficiency) (P < 0.001) and Montebello relative functional scores (P < 0.001) were also lower in PFD, compared with patients with NPFD. However, linear regression analysis showed that PFD did not predict total, motor, or FIM gain at discharge (beta = -0.11, P = 0.115; beta = -0.06, P = 0.412; beta = -0.099, P = 0.329, respectively). Upon discharge, patients with PFD achieved lower FIM scores yet maintained similar motor-FIM gains compared with patients with NPFD. CONCLUSIONS: Our study results supports the inclusion of patients with PFD in postfracture rehabilitation programs. PMID- 29794531 TI - Effectiveness of Physiotherapy Interventions on Spasticity in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The aim of the study was to examine the effectiveness of physiotherapy (PT) interventions on spasticity in people with multiple sclerosis. DESIGN: A systematic search was performed using PRISMA guidance. Studies evaluate the effect of PT interventions on spasticity were included. People with multiple sclerosis, spasticity, disability and PT interventions characteristics were extracted in included studies. Level of evidence was synthesized by the Grade of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed by calculating Hedges g at 95% confidence interval. RESULTS: A total of 29 studies were included in the review, and 25 were included in the meta analyses. The included PT interventions were exercise therapy, electrical stimulation, radial shock wave therapy, vibration, and standing. The review and meta-analyses showed different evidences of benefits and nonbenefits for PT interventions on some spasticity outcomes. The best quality evidences were for beneficial effects of exercise therapy especially robot gait training and outpatient exercise programs on self-perceived spasticity and muscle tone respectively. The review results were positive regarding the acute effects, follow-up measurements, safety, progressive MS, and nonambulatory people with multiple sclerosis. The included articles were heterogeneous and badly reported in PT interventions and people with multiple sclerosis characteristics. CONCLUSIONS: Physiotherapy interventions can be a safe and beneficial option for spasticity in people with multiple sclerosis. No firm conclusion can be drawn on overall spasticity. Further researches in different spasticity aspects are needed. PMID- 29794530 TI - Nerve Stimulation Enhances Task-Oriented Training for Moderate-to-Severe Hemiparesis 3-12 Months After Stroke: A Randomized Trial. AB - OBJECTIVE: The aim of the study was to determine whether somatosensory stimulation affects outcomes of motor training for moderate-to-severe upper limb hemiparesis less than 12 mos before stroke. DESIGN: Fifty-five adults participated in 18 intervention sessions pairing 2 hours of active (n = 33) or sham (n = 22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Wolf Motor Function Test, Action Research Arm Test, Fugl-Meyer Assessment, and Stroke Impact Scale were administered at baseline, postintervention, and 1- and 4-mo follow-up. RESULTS: Statistically significant between-groups differences favored the active condition on Wolf Motor Function Test at post (P = 0.04) and Action Research Arm Test at post (P = 0.02), 1 mo (P = 0.01), and 4 mos (P = 0.01) but favored the sham condition on Stroke Impact Scale at 1 mo (P = 0.03). There were no significant between-groups differences on Fugl-Meyer Assessment. CONCLUSIONS: Somatosensory stimulation can improve objective outcomes of motor training for moderate-to-severe hemiparesis less than 12 mos after stroke, although it needs to be determined whether the magnitude of between-groups differences in this study is clinically relevant. Future studies should investigate the intervention's impact on disability and functional recovery for this population as well as neurophysiological mechanisms underlying intervention effects. PMID- 29794532 TI - Equal Management of Equal Risks: What Should be Used as the Standard for Cervical Cancer Prevention? PMID- 29794533 TI - Retropharyngeal Steroid Use in Anterior Cervical Discectomy and Fusion. PMID- 29794534 TI - Introduction by the Guest Editor: Mobilizing the Cancer Ecosystem: The Cancer Moonshot. PMID- 29794535 TI - Catalyzing Novel Approaches to Rapid, Accurate, and Affordable Early Cancer Detection. AB - Inspired by the Cancer Moonshot, a dedicated team of professionals worked with leaders across the cancer ecosystem to look for an opportunity to radically reduce cancer mortality globally by focusing on early cancer detection. After an initial survey of cancer innovation, progress, and pitfalls, the team believed that if new rapid, affordable, and accurate early detection solutions were appropriately brought to market, it would be possible to intervene earlier when cancer is most treatable.An extensive process began, informed by dozens of experts in the cancer ecosystem. The Cancer XPRIZE team designed a prize competition where "the winning team will develop a means to rapidly, accurately, and affordably screen for early cancers where intervention can reduce human suffering."The following outlines the Cancer XPRIZE's experience using a powerful approach-the radical prize design-to catch more cancers in time to make a difference saving lives, dollars, and suffering. PMID- 29794537 TI - Progress Toward Cancer Data Ecosystems. AB - One of the recommendations of the Cancer Moonshot Blue Ribbon Panel report from 2016 was the creation of a national cancer data ecosystem. We review some of the approaches for building cancer data ecosystems and some of the progress that has been made. A data commons is the colocation of data with cloud computing infrastructure and commonly used software services, tools, and applications for managing, integrating, analyzing, and sharing data to create an interoperable resource for the research community. We discuss data commons and their potential role in cancer data ecosystems and, in particular, how multiple data commons can interoperate to form part of the foundation for a cancer data ecosystem. PMID- 29794538 TI - The First Year of the Food and Drug Administration Oncology Center of Excellence: Landmark Approvals in a Dynamic Regulatory Environment. AB - The Food and Drug Administration formally established the Oncology Center of Excellence (OCE) in January 2017, as authorized by the 21st Century Cures Act, to expedite the development and review of certain drugs, biologics, and devices for the treatment of cancer. In its first year, the OCE conducted the clinical reviews for several products, including the first 2 chimeric antigen receptor T cell therapies approved for the treatment of advanced hematologic malignancies and an in vitro diagnostic next-generation sequencing panel, FoundationOne CDx. The OCE also worked with professional societies and patient advocates on efforts to modernize clinical trial eligibility criteria, resulting in recommendations regarding minimal age, brain metastases, organ dysfunction, and human immunodeficiency virus coinfection. Altogether in 2017, the Food and Drug Administration approved 16 new drug and biologic applications, 30 supplemental drug and biologic applications, and 2 biosimilar applications in oncology. PMID- 29794536 TI - Moonshot Objectives: Catalyze New Scientific Breakthroughs-Proteogenomics. AB - Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids-DNA, RNA, and their modifications-and a focus on proteins and protein function. Proteogenomics represents a fusion of those two approaches, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function at the molecular level. Proteogenomic studies have been incorporated into multiple activities associated with the Cancer Moonshot, demonstrating substantial added value. Innovative study designs integrating genomic, transcriptomic, and proteomic data, particularly those using clinically relevant samples and involving clinical trials, are poised to provide new insights regarding cancer risk, progression, and response to therapy. PMID- 29794540 TI - Closing Knowledge Gaps to Optimize Patient Outcomes and Advance Precision Medicine. AB - Realizing the promise of precision medicine requires patient engagement at the key decision points throughout the cancer journey. Previous research has shown that patients who make the "right" decisions, such as being treated at a high volume academic medical center, for example, have better outcomes. An online survey was conducted to understand awareness of and barriers to these decision points among patients with multiple myeloma and pancreatic, lung, prostate, and metastatic breast cancers. Survey respondents were identified by 5 participating foundations (multiple myeloma: n = 86, pancreatic: n = 108, lung: n = 56, prostate: n = 50, metastatic breast: n = 86) and recruited by an e-mail or social media invitation. Descriptive analyses were calculated, and the proportion of patients from each of the 5 groups was compared for each response category for each survey item. Consistent gaps in knowledge and actions were identified across all cancers evaluated in terms of finding the right doctors/team at the right center; getting the right diagnostic testing done before beginning treatment; engaging in the right course of treatment, including clinical trials; and in sharing data. Improving awareness of and changing behavior around these 4 decision points will allow patients to receive better care and contribute to the advancement of precision medicine. PMID- 29794541 TI - Can biomarkers improve the rational use of antibiotics? AB - PURPOSE OF REVIEW: We aim to review recent literature about the use of biomarkers to guide the initiation and duration of antibiotic treatments for suspected bacterial infections. RECENT FINDINGS: Several good quality meta-analyses show that procalcitonin can be safely used to guide antibiotic-related decisions, especially for respiratory infections, thereby decreasing unnecessary antibiotic exposure. Furthermore, the use of CRP-based algorithms to guide antibiotic initiation in primary care patients with acute respiratory infections is associated with a reduction in antibiotic use without an increase in adverse events. Regarding neutrophil CD64 and serum amyloid A, more good-quality evidence is needed to assess their utility as biomarkers to tailor antibiotic use. Finally, transcriptomics, metabolomics and proteomics are promising tools for the development of tests to differentiate specific host responses to viral, bacterial and noninfectious stimuli, but such tests still need further validation. SUMMARY: Evidence shows that the use of biomarkers, procalcitonin and CRP, can safely reduce unnecessary antibiotic prescriptions in certain infectious syndromes. The clinical utility of host-based strategies such as transcriptomics, metabolomics and proteomics for the diagnosis of infectious diseases has yet to be evaluated, as well as considerations such as costs, technical complexity and result turnaround time. PMID- 29794539 TI - Data-Powered Participatory Decision Making: Leveraging Systems Thinking and Simulation to Guide Selection and Implementation of Evidence-Based Colorectal Cancer Screening Interventions. AB - A robust evidence base supports the effectiveness of timely colorectal cancer (CRC) screening, follow-up of abnormal results, and referral to care in reducing CRC morbidity and mortality. However, only two-thirds of the US population is current with recommended screening, and rates are much lower for those who are vulnerable because of their race/ethnicity, insurance status, or rural location. Multiple, multilevel factors contribute to observed disparities, and these factors vary across different populations and contexts. As highlighted by the Cancer Moonshot Blue Ribbon Panel working groups focused on Prevention and Early Detection and Implementation Science inadequate CRC screening and follow-up represent an enormous missed opportunity in cancer prevention and control. To measurably reduce CRC morbidity and mortality, the evidence base must be strengthened to guide the identification of (1) multilevel factors that influence screening across different populations and contexts, (2) multilevel interventions and implementation strategies that will be most effective at targeting those factors, and (3) combinations of strategies that interact synergistically to improve outcomes. Systems thinking and simulation modeling (systems science) provide a set of approaches and techniques to aid decision makers in using the best available data and research evidence to guide implementation planning in the context of such complexity. This commentary summarizes current challenges in CRC prevention and control, discusses the status of the evidence base to guide the selection and implementation of multilevel CRC screening interventions, and describes a multi-institution project to showcase how systems science can be leveraged to optimize selection and implementation of CRC screening interventions in diverse populations and contexts. PMID- 29794542 TI - Legionella: a reemerging pathogen. AB - PURPOSE OF REVIEW: The present review summarizes new knowledge about Legionella epidemiology, clinical characteristics, community-associated and hospital-based outbreaks, molecular typing and molecular epidemiology, prevention, and detection in environmental and clinical specimens. RECENT FINDINGS: The incidence of Legionnaire's disease is rising and the mortality rate remains high, particularly for immunocompromised patients. Extracorporeal membrane oxygenation may help support patients with severe respiratory failure. Fluoroquinolones and macrolides appear to be equally efficacious for treating Legionnaires' disease. Whole genome sequencing is an important tool for determining the source for Legionella infections and for understanding routes of transmission and mechanisms by which new pathogenic clones emerge. Real-time quantitative polymerase chain reaction testing of respiratory specimens may improve our ability to diagnose Legionnaire's disease. The frequency of viable but nonculturable organisms is quite high in some water systems but their role in causing clinical disease has not been defined. SUMMARY: Legionellosis remains an important public health threat. To prevent these infections, staff of municipalities and large buildings must implement effective water system management programs that reduce Legionella growth and transmission and all Medicare-certified healthcare facilities must have water management policies. In addition, we need better methods for detecting Legionella in water systems and in clinical specimens to improve prevention strategies and clinical diagnosis. PMID- 29794543 TI - Refractory Constipation: What is the Clinician to Do? AB - Most clinicians will agree that chronic constipation is characterized by abnormal bowel movement consistency and/or frequency plus or minus evacuation symptoms, but patient perception of constipation varies widely and includes symptoms that may or may not meet official defining criteria. Although intermittent constipation is extremely common, only a small minority of patients seek care for their symptoms. Among these patients, dissatisfaction with the currently available laxative options is not uncommon, and many patients will require specialized care for severe or refractory symptoms-especially those with abdominal pain, irritable bowel syndrome overlap, bloating or distention, and psychological comorbidities. This review outlines a physiological assessment of the patient with refractory constipation, exploring treatment options among patients with slow transit, rectal evacuation disorders, and normal transit. In addition, we explore nonlaxative approaches to normal-transit patients bothered by ongoing symptoms, with an emphasis on the biopsychosocial model of functional gastrointestinal disease and treatment of visceral hypersensitivity using neuromodulators. Finally, we propose a comprehensive evaluation algorithm for the management of patients with refractory slow-transit constipation considering surgery and examine surgical options including colectomy and cecostomy using an antegrade continent enema. PMID- 29794544 TI - Shear Wave Elastography to Assess Perineal Body Stiffness During Labor. AB - OBJECTIVES: The objective of this study was to evaluate perineal body stiffness intrapartum using shear wave elastography ultrasound and to study its association with maternal and labor characteristics. METHODS: This was a prospective observational study. Pregnant women with term pregnancy who had been admitted for labor management were recruited into the study. Transperineal shear wave elastography of perineal body was performed. Maternal and labor data were retrieved from electronic medical charts. RESULTS: Thirty-two patients' data were available for analysis. Mean (SD) melastography modulus was 15.33 (5.49). While comparing the mean elastography modulus across maternal and labor characteristics, the difference was statistically different between parity, cervical dilation, and perineal laceration presence groups (P < 0.05). The mean of elastography modulus of primiparous women with cervical dilation less than 3 cm was 21.47 kPa, whereas that of multiparous women was 13.17 kPa (P = 0.0511). Perineal laceration was more prevalent in women with stiffer perineal body. The risk of having perineal laceration compared with no perineal laceration was 29.1% higher for each additional unit increase in perineal body elastography modulus (odds ratio, 0.709; 95% confidence interval, 0.507-0.992). CONCLUSIONS: Shear wave elastography can be used to quantify perineal body stiffness. Primiparous women in early stages of labor have stiffer perineal body than multiparous women in any stage of labor and primiparous women in late stage of labor. PMID- 29794545 TI - Effect of telerehabilitation on mobility in people after hip surgery: a pilot feasibility study. AB - The goal of this study was to evaluate the effects of telerehabilitation on mobility in people following hip surgery. This feasibility pilot randomized controlled trial included a sample of 40 participants, with 22 male and 18 female patients and mean age (SD) of 67.5 (7.8) years following a surgical intervention. Participants were equally divided and randomly assigned to a telerehabilitation or control intervention group (6 weeks, 3 sessions/week). Telerehabilitation was based on video clips of common rehabilitation exercises focusing on the lower limbs. The control group received an exercise booklet. Both groups participated in physical therapy sessions, twice a week. Outcome measures included the Timed Up and Go test, 2-min walk test, 10-m walk test, sit to stand test, walking speed, and mean step length. Measurements were completed at baseline, at termination of the intervention, and at a 4-week follow-up examination. Improvements in both groups were demonstrated in all outcome measures in the postintervention evaluation. Improvements in the telerehabilitation group were greater in five of six tests compared with those achieved by the controls. The telerehabilitation group showed greater improvements in the 2-min walking test (86.1%) and walking speed (65.6%). During follow-up, the telerehabilitation group continued to improve in all outcome measures in contrast to the control group, who showed no changes in five of the six outcome measures. Telerehabilitation, a complementary treatment to standard physical therapy, generates a positive effect on mobility in people following hip surgery. PMID- 29794546 TI - Early Interventions for the Prevention of Posttraumatic Stress Symptoms in Survivors of Critical Illness: A Qualitative Systematic Review. AB - OBJECTIVES: Posttraumatic stress disorder among survivors of critical illness is of public health importance, as it is common and reduces patient quality of life. The objective of this systematic review was to collate the world's literature on interventions aimed at preventing posttraumatic stress disorder among survivors of critical illness. DATA SOURCES: We performed a search of CENTRAL, MEDLINE, EMBASE, CINAHL, and clinical trials registry platforms, with no restriction to language using a comprehensive strategy. STUDY SELECTION: Study inclusion criteria were as follows: 1) adult human subjects, 2) patients treated in an ICU setting, 3) intervention arm aimed at reducing posttraumatic stress disorder symptoms, 4) use of a control arm, and 5) an outcome measure assessing development of acute stress or posttraumatic stress disorder symptoms. DATA EXTRACTION: We performed a qualitative analysis to collate and summarize effects of identified interventions according to the recommended methodology from the Cochrane Handbook. DATA SYNTHESIS: Seventeen studies met all inclusion and no exclusion criteria. There was heterogeneity in interventions and outcome measures used. All studies had some concern for risk of bias as per the Cochrane tool for assessing risk of bias. In eight of 12 studies (67%) testing early interventions (i.e., initiated in the ICU course) and one of five studies (20%) testing delayed interventions following ICU discharge, posttraumatic stress disorder symptoms were decreased among the intervention group compared with controls. CONCLUSIONS: Despite a paucity of high-quality clinical investigations, the preponderance of evidence to date suggests that 1) posttraumatic stress disorder among survivors of critical illness may be preventable and 2) early interventions may be the most effective. PMID- 29794548 TI - Motivational Profiles and Motivation for Lifelong Learning of Medical Specialists. AB - INTRODUCTION: Medical specialists face the challenge of maintaining their knowledge and skills and continuing professional development, that is, lifelong learning. Motivation may play an integral role in many of the challenges facing the physician workforce today including maintenance of a high performance. The aim of this study was to determine whether medical specialists show different motivational profiles and if these profiles predict differences in motivation for lifelong learning. METHODS: An online questionnaire was sent to every medical specialist working in five hospitals in the Netherlands. The questionnaire included the validated Multidimensional Work Motivation Scale and the Jefferson Scale of Physician Lifelong Learning together with background questions like age, gender, and type of hospital. Respondents were grouped into different motivational profiles by using a two-step clustering approach. RESULTS: Four motivational profiles were identified: (1) HAMC profile (for High Autonomous and Moderate Controlled motivation), (2) MAMC profile (for Moderate Autonomous and Moderate Controlled motivation), (3) MALC profile (for Moderate Autonomous and Low Controlled motivation), and (4) HALC profile (for High Autonomous and Low Controlled motivation). Most of the female specialists that work in an academic hospital and specialists with a surgical specialty were represented in the HALC profile. DISCUSSION: Four motivational profiles were found among medical specialists, differing in gender, experience and type of specialization. The profiles are based on the combination of autonomous motivation (AM) and controlled motivation (CM) in the specialists. The profiles that have a high score on autonomous motivation have a positive association with lifelong learning. PMID- 29794547 TI - Constipation in critical care patients: both timing and duration matter. AB - OBJECTIVE: Most of the studies have defined constipation as a period without stool after ICU admission. We aimed to test the impact of both duration and timing of infrequent defecation in critical care patients. PATIENTS AND METHODS: We performed a prospective, bi-center, observational study. Patients were divided into three subgroups: 'not constipated', '3-5 days', and 'at least 6 days' (longest period without stool passage, respectively, shorter than 3 days, 3-5 days, and >=6 days). Furthermore, 'early' constipated patients were defined as those for whom the longest time to stool passage occurred just after ICU admission, whereas for 'late' constipated patients the longest period without stool occurred later during ICU stay. RESULTS: A total of 182 patients were included: the mean age was 67.2 years (54.4-78.9 years), 80 were women, and simplified acute physiology score II was 42 (34-52). In all, 42 (23.1%), 82 (45.1%), and 58 (31.8%) belonged to the nonconstipated, 3-5 days, or greater than or equal to 6 days subgroup of patients, respectively. Time spent under mechanical ventilation and ICU length of stay was longer in the greater than or equal to 6 days subgroups as compared with both other subgroups. ICU stay was longer in the 3-5 days subgroup as compared with the not constipated patients. Furthermore, the late patients of the greater than or equal to 6 days subgroups exhibited worse survival as compared with all other patients. CONCLUSION: Both timing and duration of infrequent defecation seem to have an impact on critical care patient's outcome, and should therefore be included in the diagnostic criteria. PMID- 29794549 TI - Tips on Collecting, Presenting, and Statistically Analyzing Data: Strategies for Avoiding Reviewer Criticisms in Education and Practice Improvement Research. PMID- 29794550 TI - Comforting Comes Full Circle. AB - Nurses' personal grief and loss experiences can enhance their ability to comfort family members of seriously ill and dying patients. Spiritual care in these situations can include empathy, listening, and sharing of Scripture when appropriate. Additionally, caring for emotional needs of patients in critical care situations also may enable a nurse to resolve personal grief experiences. PMID- 29794551 TI - Barriers to Preceptor Placement for Nurse Practitioner Students. AB - Advanced practice registered nurses (APRNs) are positioned to fill healthcare gaps in the looming primary care provider shortage, if clinical educational needs can be met. Issues with preceptor placements for APRNs have been hotly debated in nursing education but not well studied. This article presents a case study of a quality improvement project, describing the experiences of a Clinical Preceptor Placement Coordinator for APRN students for a small Midwestern university. Barriers identified in finding preceptor placements for students are delineated, and suggestions for solutions and further research are given to address this growing problem. PMID- 29794552 TI - Drug-resistant cytomegalovirus: clinical implications of specific mutations. AB - PURPOSE OF REVIEW: Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management. RECENT FINDINGS: Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase. SUMMARY: Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease. PMID- 29794553 TI - Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease? AB - PURPOSE OF REVIEW: The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. RECENT FINDINGS: A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. SUMMARY: Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease. PMID- 29794555 TI - The Association Between Long Working Hours and High-Sensitivity C-Reactive Protein in Older Aged Individuals: The Korea National Health and Nutrition Examination Survey (KNHANES) 2015. AB - OBJECTIVE: The objective of this study was to show the association of high sensitivity C-reactive protein (hs-CRP) level with working hours in different age groups. METHODS: We used data from Korean National Health and Nutrition Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) of variables for elevated hs-CRP (>3.0 mg/L) were generated with logistic regression models. Significant variables were verified with an adjusted multivariate logistic model after stratification of age groups. RESULTS: Working for more than 55 hours per week was associated with elevated hs-CRP level in the old-ages group (>= 60 years old: OR 2.18, 95% CI 1.07 to 4.45). Working for 40 to 55 hours per week was associated with decreased hs-CRP in the young-ages group (OR 0.58, 95% CI 0.37 to 0.93). CONCLUSION: Working hours appear to influence the levels of hs-CRP in individuals aged older than 60 years. PMID- 29794554 TI - Pertinence of Titration and Age-Based Dosing Methods for Electroconvulsive Therapy: An International Retrospective Multicenter Study. AB - BACKGROUND: Although the dosage of electroconvulsive therapy (ECT) stimulus has a major impact on the efficacy and safety of this treatment, the method used to determine an optimal dosage remains a matter of debate. OBJECTIVE: We investigated factors influencing the seizure threshold (ST) in a large-sample study and compared age-based and titration dosing methods in terms of charge. METHODS: A retrospective study examined data from 503 patients across France and Canada. The patients underwent right unilateral (RUL) or bitemporal (BT) ECT during a titration session before undergoing ECT. Seizure threshold and charge differences between age-based and titration-predicted methods were derived for each RUL and BT patient and compared according to sex, age, and anesthetic agents. RESULTS: Based on our results, ST is a function of electrode placement, sex, age, and anesthetic agents. Titration and age-based methods led to completely different patterns of charges for the same electrode placement, especially in elderly and in women in the RUL group. Regression models showed that differences between the age-based and titration methods varied with respect to age, sex, and anesthetic agent. Specifically, significant effects of sex and age were observed for RUL ECT and of sex and anesthetics for BT ECT. CONCLUSIONS: This study revealed that several factors significantly influence the prediction of ECT dose, depending on individuals and treatment modalities. Caution should be exercised when using nonindividualized methods to calculate ST. PMID- 29794556 TI - A review of recent literature on the impact of parental substance use disorders on children and the provision of effective services. AB - PURPOSE OF REVIEW: To provide an update of recent studies of the incidence and impact of parental substance use disorders (SUDs) on children, and to identify effective treatment programs to assist parents with SUDs and their children. RECENT FINDINGS: Children of parents with alcohol and drug use disorders (COPADs) suffer from physical, mental and behavioral problems at higher rates than other children and are more likely to develop their own SUDs in adolescence. Parenting styles and familial dysfunction contribute to the intergenerational transmission of SUDs. Studies of the negative effects of parental SUDs on children identified the effects of inconsistent, disengaged or harsh parenting practices on mother child bonding. Exposure to violence and father's hostility contribute to children's externalizing and internalizing behaviors. Family- based intervention programs, as well as programs for mothers with SUDs and their young children, have shown positive results. For high-risk families with multiple needs, the ongoing support of multidisciplinary services is required. SUMMARY: Parental SUDs have a profound impact on their children, including intergenerational transmission of SUDs. A variety of interventive programs are being studied in order to devise effective programs to assist these children. PMID- 29794558 TI - Covariables and types of abnormal left ventricular geometry in nonelderly ischemic stroke survivors: the Norwegian Stroke in the Young Study. AB - BACKGROUND: Abnormal left ventricular (LV) geometry types, like LV hypertrophy (LVH) and concentric remodelling, are independently associated with impaired prognosis in hypertension. Little is known about the prevalence and covariables of abnormal LV geometry types in younger ischemic stroke patients. METHODS: We used clinical and echocardiographic data from 280 patients aged 15-60 years included in the Norwegian Stroke in the Young Study. LVH was defined as LV mass index greater than 46.7 g/m in women and greater than 49.2 g/m in men. Concentric remodelling was considered present if posterior wall thickness/LV internal diameter ratio at least 0.43 in the absence of LVH. Arterial damage was assessed by mean common carotid intima-media thickness (IMT) and carotid-femoral pulse wave velocity (PWV). RESULTS: Abnormal LV geometry was found in 37% of patients. Concentric remodelling was the most prevalent abnormal LV geometry type, found in 21%, whereas LVH was found in 16%. In multivariable logistic regression analyses, LVH was associated with increased PWV, higher BMI and creatinine, and presence of diabetes and hypertension (all P < 0.05), whereas concentric remodelling was associated with higher mean carotid IMT independent of age (both P < 0.05). CONCLUSION: In ischemic stroke survivors less than 60 years of age, abnormal LV geometry was common, found in 37%. Presence of abnormal LV geometry may contribute to the known higher risk of recurrent cardiovascular events in ischemic stroke survivors. PMID- 29794557 TI - Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder. AB - OBJECTIVE: Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. A randomized, placebo-control, crossover human laboratory trial advanced IBUD development for alcohol use disorder and found that IBUD reduced tonic levels of alcohol craving. Given the importance of considering medication effects on other appetitive behavior, the present study tested the effect of IBUD (50 mg bid) on food craving. METHOD: The present study was a secondary data analysis of the trial of IBUD in non-treatment seekers with alcohol use disorder (N = 19). High fat/high-sugar food craving was measured daily. Moreover, because substantial literatures show that small alcohol doses and psychological stress increase eating of high-fat/high-sugar food, craving for high-fat/high-sugar food was measured after alcohol infusion and stress reactivity. RESULTS: Results indicated that IBUD did not alter tonic high-fat/high-sugar food craving. Alcohol infusion did not generally increase high-fat/high-sugar food craving but psychological stress did. Likewise, IBUD did not affect high-fat/high-sugar food craving after alcohol infusion but IBUD did increase high-fat/high-sugar food craving after psychological stress. Follow-up analyses revealed that, among individuals with lower depressive symptomatology, IBUD compared to placebo heightened the effect of psychological stress on high-fat/high-sugar food craving. CONCLUSIONS: These results advance the development of IBUD for addiction indications by demonstrating that IBUD compared to placebo does not suppress other appetitive responses, namely craving for high-fat/high-sugar food among individuals with alcohol use disorder. PMID- 29794559 TI - Blood pressure response to maximal dynamic exercise testing in an athletic population. AB - OBJECTIVE: Exaggerated blood pressure (BP) response to exercise testing has been linked to left ventricular hypertrophy and myocardial fibrosis in competitive athletes. Due to frequent training, athletes are particularly exposed to high BP levels, but data on the magnitude and distribution of BP response to exercise in athletic populations is scarce. METHODS: Cycle ergometry was performed in 2419 healthy competitive adolescent, professional and master athletes (age 26 +/- 12 years, range 9-74, 27% women, 84 disciplines) for preparticipation screening. Fulfilling both subjective and at least two out of three objective exhaustion criteria (maximal heart rate >85% predicted, lactate >=7 mmol/l, rate of perceived exertion >=17) was required. Echocardiography was also performed. RESULTS: Maximal workload was 305 +/- 59 W (mean +/- SD) in men and 218 +/- 40 in women. SBP increased significantly (men, Delta80 +/- 20; women, Delta67 +/- 16 mmHg; P < 0.001) to 204 +/- 22 (men) and 180 +/- 17 mmHg (women). DBP changed minimally (men: Delta0 +/- 9, women: Delta2 +/- 8 mmHg). The upper normative limit of SBP in men was 247 [95% CI 245-249; women: 214 (212-216) mmHg]. ESC guidelines of upper limits of maximal SBP were exceeded in 43% in men (>210 mmHg) and 28% in women (>190 mmHg). SBP response was more pronounced in endurance athletes, whereas DBP was slightly higher in strength athletes. Among cardiac dimensions, the strongest association for maximal SBP was found for left ventricular mass (r = 0.489; P < 0.001). CONCLUSION: SBP response to exercise testing is markedly exaggerated particularly in male endurance athletes. The prognostic significance of these findings regarding long-term cardiovascular alterations requires further clarification. PMID- 29794560 TI - Genetic effects on bone health. AB - PURPOSE OF REVIEW: In recent years, the lower costs of arrays and sequencing technologies, and the better availability of data from genome-wide association studies (GWASs) have led to more reports on genetic factors that are associated with bone health. However, there remains the need for a summary of the newly identified genetic targets that are associated with bone metabolism, and the status of their functional characterization. RECENT FINDINGS: GWASs revealed dozens of novel genetic loci that are associated with bone mineral density (BMD). Some of these targets have been functionally characterized, although the vast majority have not. Glypican 6, a membrane surface proteoglycan involved in cellular growth control and differentiation, was identified as a novel determinant of BMD and represents a possible drug target for treatment of osteoporosis. Pathway analysis also showed that cell-growth pathways and the SMAD proteins associated with low BMD. SUMMARY: Hits that were significantly associated with BMD in different studies represent likely candidates (e.g. SOST, WNT16, ESR1 and RANKL) for functional characterization and development of osteoporosis treatments. Indeed, currently available treatment for osteoporosis (antibody against RANKL) appeared a significant target in four recent GWAS studies indicating their applicability and importance for future treatment development. PMID- 29794561 TI - No association of BRD1 and ZBED4 polymorphisms with schizophrenia in the Chinese Han population. AB - The distal long arm of chromosome 22 (22q13.3) may harbor genes implicated in schizophrenia. This is evidenced by various genetic mapping studies. BRD1 and its neighboring gene ZBED4, both located within this region, have repeatedly been found to be associated with schizophrenia in the Caucasian population. In this study, we chose seven SNPs (two BRD1 SNPs, five ZBED4 SNPs) to carry out an association study between these two genes and schizophrenia in the Chinese population. However, no significant result was obtained, which was consistent with the Japanese population. Taken together, we could conclude that BRD1 and ZBED4 might be population specific in schizophrenia and may not account for a substantial proportion of genetic risk for schizophrenia in the Asian population. PMID- 29794562 TI - Tumour-infiltrating lymphocytes, programmed death ligand 1 and cyclooxygenase-2 expression in skin melanoma of elderly patients: clinicopathological correlations. AB - Age is an important prognostic factor in melanoma; notably, elderly patients tend to present with advanced stage skin melanoma (SM) and worse outcome. Moreover, SM is an immunogenic cancer, and its interaction with the aging immune system could have an effect on biologic behaviour of this disease. Tumour-infiltrating lymphocytes (TILs) could represent the host response in SM; it has been shown that higher grade of TILs is associated with better survival. Moreover, programmed death ligand 1 (PD-L1) and cyclooxygenase-2 (COX-2) are potential markers of host immune response and inflammation. We retrospectively reviewed 113 consecutive cases of early-stage SM that occurred in patients aged greater than or equal to 65 years at the time of diagnosis, followed between January 2010 and March 2014 at the University and General Hospital of Udine, Italy. The aim of this study was to evaluate TILs grade, PD-L1 expression on TILs and tumour expression of PD-L1 and COX-2 and their prognostic value in elderly patients with early SM. A better disease-free survival as well as melanoma-specific survival (MSS) was significantly associated with TILs [hazard ratios (HR): 0.41, 95% confidence interval (CI): 0.20-0.84, P=0.02 and HR: 0.37, 95% CI: 0.17-0.82, P=0.01, respectively]. PD-L1 positivity on TILs was associated with a better MSS (HR: 0.41, 95% CI: 0.17-0.97, P=0.04). Moreover, among patients with TILs, those showing COX-2 positivity on tumour cells and no PD-L1 expression on TILs had a worse disease-free survival and MSS (HR: 5.18, 95% CI: 1.33-20.23, P=0.018; HR: 6.21, 95% CI: 1.20-32.24, P=0.03; respectively). Immune and inflammatory markers deserve further investigation in aging patients with melanoma. PMID- 29794563 TI - Ultrasound-guided single injection versus continuous sciatic nerve blockade on pain management and mobilisation after total knee arthroplasty (CoSinUS trial): A randomised, triple-blinded controlled trial. AB - BACKGROUND: Combining continuous femoral nerve blockade with single injection sciatic nerve blockade is standard peripheral nerve block practice for total knee arthroplasty (TKA) during the first 24 postoperative hours. OBJECTIVES: To assess the analgesic benefits and mobilisation capability of continuous sciatic blockade in conjunction with continuous femoral nerve blockade for 72 h after arthroplasty. DESIGN: Randomised, triple-blinded controlled trial. SETTING: Single-Centre, German University Hospital. PATIENTS: In total, 50 patients receiving continuous femoral nerve blockade (5 ml h ropivacaine 0.2%) for TKA under general anaesthesia. INTERVENTIONS: Patients were randomised to receive a sciatic nerve catheter with an initial dose of 10 ml ropivacaine 0.2% followed by either continuous double-blinded application of 5 ml h ropivacaine 0.2% (CO) or 5 ml h saline infusion (SIN). MAIN OUTCOME: Measures primary endpoint: cumulative morphine consumption until 48 h postoperatively. Further endpoints included morphine consumption, pain scores, mobilisation, dynamometry until postoperative day 3. RESULTS: Median [25th to 75th percentiles] cumulative morphine consumption at postoperative day 2 differed significantly between groups (CO 15 mg [11 to 25] versus SIN, 43 mg [27 to 67.5, P < 0.0001) in the 48 patients in the final analysis. Overall pain scores were comparable at rest and during stress at each time point. However, significantly higher pain scores of the popliteal fossa were observed in the SIN group. Mobilisation was comparable between groups. CONCLUSION: This trial demonstrates the superior analgesic effects of continuous sciatic nerve block compared with a single injection in combination with continuous femoral blockade during the first 72 h after TKA. However, mobilisation capability was impaired in both groups. Improved pain control from two catheters needs to be balanced against the potential risks of impaired mobilisation and patient falls. TRIAL REGISTRATION: DRKS - German clinical trials register (no: DRKS00010152). PMID- 29794564 TI - Examining prescriber perceptions of statin therapy and the potential implications these perceptions may have on guideline adherence. AB - Not all psychiatric inpatients who are candidates for statin therapy are prescribed statin medication. It is unclear whether this is because of prescriber guideline uncertainty or purposeful avoidance because of other reasons. This study aims to determine prescribers' perceptions of recent cholesterol treatment guidelines, and whether their prescribing may be influenced by recent, potentially oversimplified headlines in the media. PMID- 29794565 TI - Heritability of Age-Related Hearing Loss in Middle-Aged and Elderly Chinese: A Population-Based Twin Study. AB - OBJECTIVES: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations. DESIGN: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.55 years). Pure-tone air-conducted hearing thresholds in each ear were measured at the frequencies of 0.5, 1.0, 2.0, 4.0, 8.0, and 12.5 kHz with a diagnostic audiometer. Univariate and multivariate twin models were fitted to evaluate heritability and genetic correlations. RESULTS: Our data showed a reverse J-shaped pattern of BEHLs at six frequencies by age and sex. Univariate analysis showed that the heritability of BEHLs at the frequencies between 2.0 and 12.5 kHz ranged from 47.08 to 54.20%, but the heritability at the frequencies of 0.5 and 1.0 kHz was 1.65% and 18.68%, respectively. The heritability of pure-tone average at the middle and high frequencies was 34.77% and 43.26%, respectively. Multivariate analysis showed significant genetic correlations among BEHLs at all six frequencies, with the correlation coefficients ranging from 0.48 to 0.83 at middle frequencies, and from 0.46 to 0.75 at high frequencies. CONCLUSIONS: This population-based twin study suggests that genetic factors are associated with age-related hearing loss at middle and high frequencies among middle-aged and elderly Chinese. PMID- 29794566 TI - Effects of Amplification and Hearing Aid Experience on the Contribution of Specific Frequency Bands to Loudness. AB - OBJECTIVES: The primary aim of this study is to describe the effect of hearing aid amplification on the contribution of specific frequency bands to overall loudness in adult listeners with sensorineural hearing loss (SNHL). Results for listeners with SNHL were compared with results for listeners with normal hearing (NH) to evaluate whether amplification restores the normal perception of loudness for broadband sound. A secondary aim of this study is to determine whether the loudness perception of new hearing aid users becomes closer to normal over the first few months of hearing aid use. It was hypothesized that amplification would cause the high-frequency bands to contribute most to the perception of loudness and that this effect might decrease as new hearing aid users adapt to amplification. DESIGN: In experiment 1, 8 adult listeners with SNHL completed a two-interval forced-choice loudness task in unaided and aided conditions. A control group of 7 listeners with NH completed the task in the unaided condition only. Stimuli were composed of seven summed noise bands whose levels were independently adjusted between presentations. During a trial, two stimuli were presented, and listeners determined the louder one. The correlation between the difference in levels for a given noise band on every trial and the listener's response was calculated. The resulting measure is termed the perceptual weight because it provides an estimate of the relative contribution of a given frequency region to overall loudness. In experiment 2, a separate group of 6 new hearing aid users repeated identical procedures on 2 sessions separated by 12 weeks. RESULTS: Results for listeners with SNHL were similar in experiments 1 and 2. In the unaided condition, perceptual weights were greatest for the low-frequency bands. In the aided condition, perceptual weights were greatest for the high frequency bands. On average, the aided perceptual weights for listeners with SNHL for high-frequency bands were greater than the unaided weights for listeners with NH. In experiment 2, hearing aid experience did not have a significant effect on perceptual weights. CONCLUSIONS: The high frequencies seem to dominate loudness perception in listeners with SNHL using hearing aids as they do in listeners with NH. However, the results suggest that amplification causes high frequencies to have a larger contribution to overall loudness compared with listeners with NH. The contribution of the high frequencies to loudness did not change after an acclimatization period for the first-time hearing aid users. PMID- 29794567 TI - Ketamine and electroconvulsive therapy: so happy together? AB - PURPOSE OF REVIEW: Anesthetics, such as thiopental, methohexital, propofol and ketamine have been used to induce unconsciousness for electroconvulsive therapy (ECT), each with its advantages and disadvantages. Only until recently was it discovered that ketamine may have inherent antidepressant effects. We reviewed the side effect profile of ketamine and examined the literature for whether or not ketamine augments the antidepressant effects of ECT. RECENT FINDINGS: Systematic reviews and meta-analyses of randomized controlled trials of the potential benefits of adding ketamine to ECT treatment have generated varied conclusions. Currently there is a lack of clear evidence that ketamine with ECT is more efficacious than ECT alone. SUMMARY: Large, multicenter randomized controlled trials are needed to further investigate the potential advantages of adding ketamine to ECT for patients with severe or refractory depression. The addition of ketamine to ECT treatment may have some early beneficial effect in patients with acute depressive disorders. Most likely, ECT itself is responsible for lasting remission from severe depression. Ketamine's side effect profile may be undesirable in certain patient populations, and so the risks and benefits of the addition of this drug to ECT treatment must be weighed. PMID- 29794568 TI - Healthcare Professionals' and Patients' Views of Discussing Sexual Well-being Poststroke. AB - PURPOSE: Stroke can cause physical and emotional problems affecting sexual well being; healthcare professionals (HCPs) are often uncomfortable discussing this topic with patients. We explored the perspectives of HCPs and stroke survivors about barriers to discussing sexual well-being poststroke. DESIGN: A mixed methodology was employed. METHODS: A postal survey of stroke survivors (n = 50), a focus group with HCPs on a stroke unit (n = 6), and a focus group with community-living stroke survivors (n = 6) were used in this study. Focus group data were analyzed thematically. FINDINGS: No patient surveyed (60% response rate) had discussed sexual well-being with an HCP. Focus groups revealed barriers on multiple levels: structural, HCP, patient, and professional-patient interface. CONCLUSIONS: Healthcare professionals were poorly trained, adopted a passive role, and addressed sexual activity based on individual beliefs rather than having an agreed team approach. CLINICAL RELEVANCE: Relatively simple steps like inclusion in policy, training to empower HCPs, and the provision of written information for patients could help to improve practice. PMID- 29794569 TI - Risk Factors, Depression, and Drugs Influencing Sexual Activity in Individuals With and Without Stroke. AB - PURPOSE: The aim of the study was to analyze factors affecting sexual activity in individuals with and without stroke, ages 40-59 years, in a national, cross sectional, population-based sample derived from the National Health and Nutrition Examination Survey (NHANES). DESIGN: Descriptive, cross-sectional survey. METHODS: Data were obtained from the NHANES (2011-2012) data set from individuals (N = 3,649) completing items related to cardiovascular risk factors, drugs, and sexual activity. Data were analyzed using chi-square, t tests, and logistic regression. FINDINGS: Overall, number of drugs, smoking, and depression significantly predicted sexual activity. When comparing sexually active to not sexually active, those with stroke had significantly less sexual activity (t = 2.822, p = .005) and reduced sexual activity per week or month (chi = 16.275, p = .005, df = 4). Those taking angiotensin-converting enzyme inhibitors and statins had reduced sexual activity. CONCLUSIONS/CLINICAL RELEVANCE: Findings illustrate the importance of risk factor modification and nurses engaging in sexual assessment, education, and counseling to support sexual quality of life in younger individuals with stroke. PMID- 29794570 TI - An Exploration of Sensation Seeking in Persons With Disabilities in Rehabilitation. AB - PURPOSE: This study reports the findings of a study about sensation-seeking or high-risk/challenging sports in persons who have disabilities. DESIGN: Exploratory, cross-sectional, and descriptive. METHODS: Two hundred and twenty three recruitment e-mails were sent to potential participants. Data were collected through Qualtrics. FINDINGS: Mean score for Contextual Sensation Seeking Questionnaire for Skiing and Snowboarding (M = 30.21, SD = 8.18) was significantly lower than a sample of able-bodied skiers and snowboarders, t(239) = 2.75, p = .006. Mean for impulsive sensation seeking was lower than the same sample of able-bodied athletes cited in a previous study, t(240) = 4.56, p = .001. Means for the Zuckerman Kuhlman Personality Questionnaire subscales were impulsivity (M = 1.98, SD = 4.05) and sensation seeking (M = 6.75, SD = 2.68). CONCLUSIONS: This group scored lower in sensation seeking compared to able-bodied high-risk/challenging sports activities participants. Sensation seeking is not a motivating factor in this sample. CLINICAL RELEVANCE: Nurses could encourage rehabilitation patients to engage in challenging activities for personal and group mastery. PMID- 29794571 TI - Perioperative Hyperchloremia and its Association With Postoperative Acute Kidney Injury After Craniotomy for Primary Brain Tumor Resection: A Retrospective, Observational Study. AB - BACKGROUND: Hyperchloremia is known to influence postoperative outcomes and may result in postoperative acute kidney injury (AKI). This study sought to investigate whether hyperchloremia was associated with postoperative AKI in patients who underwent surgery for primary brain tumor resection. MATERIALS AND METHODS: This is a retrospective, observational study of patients who underwent craniotomy for primary brain tumor resection at a single tertiary care hospital between January 2005 and October 2017. Maximum levels of serum chloride (mmol/L) measured on postoperative days (PODs) 0 to 3 and increase in serum chloride (mmol/L), (maximum serum chloride-baseline serum chloride before surgery) were measured. We examined whether perioperative hyperchloremia was associated with postoperative AKI during PODs 0 to 3. Univariate and multivariate logistic regression analyses were used in this study. RESULTS: A total of 726 patients were included in the analysis; of these, 39 (5.4%) were diagnosed with postoperative AKI during PODs 0 to 3. The risk of postoperative AKI was associated with maximum chloride levels (odds ratio, 1.10; 95% confidence interval, 1.02-1.19; P=0.015) and with an increase in serum chloride levels during PODs 0 to 3 (odds ratio, 1.11; 95% confidence interval, 1.04-1.19; P=0.004). CONCLUSIONS: Our study shows that perioperative hyperchloremia during PODs 0 to 3 was associated with an increased risk of postoperative AKI during this period after craniotomy for primary brain tumor resection. PMID- 29794572 TI - Fast Ablation of Anogenital Warts of the Urinary Meatus by Low-dose Ingenol Mebutate Gel. AB - Therapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate gel. PMID- 29794573 TI - A Retrospective Analysis of the Safety Profile of Intravenous Immunoglobulin in 1176 Patients Receiving Home Infusion Therapy. AB - OBJECTIVES: This analysis assessed the safety of intravenous immunoglobulin (IVIg) in the treatment of patients with neuroimmunological and immunological disorders in a home-based setting. METHODS: Adverse reactions (ARs) were assessed in a retrospective review of 1176 patients receiving 28,677 home-based IVIg infusions between 1996 and 2013. RESULTS: Of 1176 patients, 648 (55.1%) experienced IVIg-related ARs; 536 (45.6%) were mild, 78 (6.6%) moderate, and 34 (2.9%) severe. Thirty-seven (3.1%) patients were hospitalized because of ARs; of these, headache was most common (51.4%). Mean number of ARs per patient increased from 1.4 (low dose) to 3.6 (high dose). Incidence of ARs increased from 41% in the first 5-year moving average in 2003 to 65% in 2008. The number of ARs correlated with the number of infusions (rho = 0.24; P < 0.001) and the average IVIg dose (rho = 0.10; P < 0.001). CONCLUSIONS: Low- and high-dose IVIg were safe and well tolerated with a few serious ARs in patients with neuroimmunological and immunological disorders. PMID- 29794574 TI - Lumbosacral Radiculoplexopathy as the Initial Presentation of Lymphoma: A Report of 4 Cases. AB - OBJECTIVES: To evaluate the clinical, laboratory, and radiological features of 4 cases of biopsy-proven lymphomatous lumbosacral radiculoplexopathy. METHODS: Retrospective chart review. RESULTS: All patients suffered from diffuse large B cell lymphoma. A mean diagnostic delay of 10 months was encountered. Presenting symptoms in all 4 patients included back pain, radicular leg pain, and leg weakness, similar to spondylotic radiculopathy. Electrodiagnostic study showed axon loss radiculoplexopathy and magnetic resonance imaging of the lumbar spine or pelvis demonstrated nerve or nerve root enhancement. Increased uptake by lumbosacral roots/plexus on fluorodeoxyglucose-positron emission tomography aided diagnosis in 3 cases. Cytology was positive in 1 of 10 cerebrospinal fluid samples. Combined chemotherapy and radiation treatment led to clinicoradiological improvement, with residual neurological symptoms in all patients. CONCLUSIONS: Lymphomatous lumbosacral radiculoplexopathy should be considered in patients with progressive lumbosacral radicular symptoms. Magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography, but not cerebrospinal fluid, are helpful in achieving early diagnosis. Treatment responses seem favorable. PMID- 29794575 TI - Distinct Clinical and Genetic Findings in Iranian Patients With Glycogen Storage Disease Type 3. AB - OBJECTIVES: Glycogen storage disease type 3 (GSD-III) is a rare inherited metabolic disorder caused by glycogen debranching enzyme deficiency. Various pathogenic mutations of the AGL gene lead to abnormal accumulation of glycogen in liver, skeletal, and cardiac muscles. Here, we report distinct clinical and genetic data of Iranian patients with GSD-III. METHODS: Clinical and laboratory data of 5 patients with GSD-III were recorded. Genetic investigation was performed to identify the causative mutations. RESULTS: Three patients had typical liver involvement in childhood and one was diagnosed 2 years after liver transplantation for cirrhosis of unknown etiology. Four patients had vacuolar myopathy with glycogen excess in muscle biopsy. All patients had novel homozygous mutations of the AGL gene namely c.378T>A, c.3295T>C, c.3777G>A, c.2002-2A>G, and c.1183C>T. CONCLUSIONS: This is the first comprehensive report of patients with GSD-III in Iran with 2 uncommon clinical presentations and 5 novel mutations in the AGL gene. PMID- 29794576 TI - Case of Anti-Single Recognition Particle-Mediated Necrotizing Myopathy After Influenza Vaccination. AB - Immune-mediated necrotizing myopathy is a very rare inflammatory disease affecting skeletal muscles. Immune-mediated necrotizing myopathy may be associated with myositis-specific autoantibodies including anti-single recognition particle and anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase, infectious agents (HIV or hepatitis C), other connective tissue disorders (such as scleroderma), and malignancy. We reported a 28-year-old healthy woman presented with subacute onset ascending muscle weakness 2 weeks after an annual influenza vaccination. Cerebral Spinal Fluid study showed normal cell counts with elevated protein and nerve conduction study showed reduced diffuse compound muscle action potential amplitudes suggesting a diagnosis of Guillain-Barre syndrome. Despite treatment using intravenous immunoglobulin, her condition continued to get worse with new bulbar and respiratory muscle weakness. Eventually, the diagnosis of anti-single recognition particle-mediated necrotizing myopathy was made based on elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing. Our patient responded to the combination of intravenous immunoglobulin, prednisone, and anti CD20 monoclonal antibody, rituximab. PMID- 29794577 TI - What is in the Myopathy Literature? AB - This update covers the results of a randomized, placebo-controlled study that provides evidence that lamotrigine is effective in treating nondystrophic myotonias. Next, an overview of adverse effects of immune checkpoint inhibitors is provided, and the association of autoimmune myopathy and these monoclonal antibody therapies is discussed in light of recent reports. Last, the utility of electrodiagnostic testing in patients with intensive care unit weakness is addressed with emphasis on the high sensitivity and specificity of prolonged compound muscle action potential amplitudes in diagnosing critical illness myopathy. PMID- 29794578 TI - Fisher-Pharyngeal-Cervical-Brachial Overlap Syndrome With Novel Ganglioside Antibodies. AB - Several variants of Guillain-Barre syndrome have been described. The Fisher syndrome (FS) presents with ataxia, areflexia, and ophthalmoparesis. The pharyngeal-cervical-brachial (PCB) variant presents with bulbar weakness, along with arm and neck weakness. The 2 variant syndromes can overlap. Both the isolated and overlap syndromes respond to immunomodulatory treatment, thus are important to recognize clinically. Ganglioside antibodies are detectable in the variant syndromes and may aid in their diagnosis. The FS typically is associated with anti-GQ1b antibodies, and PCB is typically associated with anti-GT1a antibodies, whereas the overlap syndrome may have both ganglioside antibody subtypes. We present a case of overlap FS-PCB syndrome with a novel ganglioside antibody profile of GM1 and GD1b antibodies, which typically are associated with other variant syndromes. This case suggests the need for all ganglioside antibodies to be tested in suspected variant Guillain-Barre syndromes. The antibodies may prove especially useful in cases in which the clinical diagnosis is ambiguous. PMID- 29794579 TI - Novel Mutation in Anoctamin 5 Gene Causing Limb-Girdle Muscular Dystrophy 2L. AB - We report a 49-year-old man who presented with a history of asymmetric weakness. His neurological examination and electromyogram testing suggested the presence of a myopathy. A muscle biopsy confirmed the presence of a myopathy with several lobulated, whorled and ring fibers, and it showed no evidence of inflammation. Genetic testing of more than 50 genes known to cause myopathy was performed and demonstrates the presence of the common founder mutation in ANO5 gene c.191dupA, which he inherited from his unaffected father. In addition, he inherited a novel mutation, c.1063C>T (p.L355F) in exon 11 of ANO5 gene from his unaffected mother. The founder mutation is a known pathogenic variant and, based on our protein modeling analysis, the novel c.1063C>T (p.L355F) variant is likely pathogenic. This indicates that he is a compound heterozygote, providing strong support for the diagnosis of limb-girdle muscular dystrophy 2L. PMID- 29794580 TI - Novel TTN Mutation Causing Congenital Myopathy. PMID- 29794582 TI - "Acquired" Type Castellvi-IIIa Lumbarization Transformed From Castellvi-IIa Following Discectomy and Fusion at Lumbosacral Level: A Case Report. AB - STUDY DESIGN: A retrospective case report. OBJECTIVE: To report a case that transformed from type Castellvi-IIa sacralization to type Castellvi-IIIa after decompression and fusion surgery at transitional disc (TD). SUMMARY OF BACKGROUND DATA: Traditionally, lumbosacral transitional vertebra has been regarded as a congenital anomaly. No literature has ever reported that transformation from one type lumbosacral transitional vertebra to another would happen after birth. METHODS: A 60-year-old man presented to our department with the complaint of low back pain and left sciatic pain, and was diagnosed of lumbar disc herniation at L4-5 and L5-S1 levels. Lumbar digital radiography revealed an anomalous articulation formed between sacrum and enlarged right L5 transverse process, exhibiting a typical Castellvi-IIa sacralization. Dynamic lateral radiographs showed mobilization existed at L5-S1 disc which was TD. The patient received posterior lumbar interbody fusion (PLIF) surgery at L4-5 and L5-S1 levels. Postoperative computed tomography examinations were taken to identify the progress of solid fusion at the operated segments. RESULTS: After surgery, the patient's symptoms alleviated obviously. As solid fusion developed at intended interbody regions with time, we found that bony bridge passed through the patient's anomalous articulation region gradually, and finally, complete osseous fusion of the right L5 transverse process to the sacrum developed 1 year after surgery. CONCLUSION: Following PLIF surgery at TD segment on a Castellvi-IIa Sacralization case, "acquired" transformation to Castellvi-IIIa might develop. LEVEL OF EVIDENCE: 5. PMID- 29794583 TI - Adjacent Segment Disease After Single Segment Posterior Lumbar Interbody Fusion for Degenerative Spondylolisthesis: Minimum 10 Years Follow-up. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to investigate the incidence of adjacent segment disease (ASD) at 2, 5, and 10 years after primary posterior lumbar interbody fusion (PLIF), and clinical features of ASD. SUMMARY OF BACKGROUND DATA: Few reports have examined ASD after PLIF with more than 10 years of follow-up. Furthermore, no reports have examined limited conditions of preoperative pathology, fusion segment, and fusion method with long follow-up. METHODS: Data were reviewed for 128 patients who underwent single segment PLIF for L4 degenerative spondylolisthesis and could be followed for at least 10 years. Mean age at the time of surgery was 63 years, and mean follow-up was 12.4 years. Follow-up rate was 62.4%. ASD was defined as radiological ASD (R ASD), radiological degeneration adjacent to the fusion segment by plain X-rays and magnetic resonance imaging (MRI); symptomatic ASD (S-ASD), a symptomatic condition due to neurological deterioration at the adjacent segment degeneration; and operative ASD (O-ASD), S-ASD requiring revision surgery. RESULTS: Incidences of each ASD at 2, 5, and 10 years after primary PLIF were 19%, 49%, and 75% for R ASD, 6%, 14%, and 31% for S-ASD, and 5%, 9%, and 15% for O-ASD, respectively. O ASD incidence was 24% at final follow-up. O-ASD peak was bimodal, at 2 and 10 years after primary PLIF. O-ASD was mainly observed at the cranial segment (77%), followed by the caudal segment (13%) and both cranial and caudal segments (10%). With respect to O-ASD pathology, degenerative spondylolisthesis was observed in 52%, spinal stenosis in 39%, and disc herniation in 10%. CONCLUSION: Incidences of R-ASD, S-ASD, and O-ASD at 10 years after primary PLIF were 75%, 31%, and 15%, respectively. With respect to O-ASD pathology, degenerative spondylolisthesis at the cranial segment was the most frequent. LEVEL OF EVIDENCE: 4. PMID- 29794581 TI - Adjacent Disc Degeneration After Lumbar Total Disc Replacement or Nonoperative Treatment: A Randomized Study with 8-year Follow-up. AB - STUDY DESIGN: A randomized controlled multicenter trial with 8-year follow-up. OBJECTIVE: The aim of this study was to assess the long-term development of adjacent disc degeneration (ADD) after lumbar total disc replacement (TDR) or nonoperative treatment, and to analyze the association between ADD development and clinical outcome. SUMMARY OF BACKGROUND DATA: TDR was introduced as a motion preserving alternative to spinal fusion, which has been reported to increase the risk of ADD. However, ADD may develop naturally regardless of any surgery, and no randomized study has assessed the long-term development of ADD after TDR versus nonoperative treatment. METHODS: The study included 126 of the 173 patients with chronic low back pain (LBP) originally included in a randomized study comparing TDR with multidisciplinary rehabilitation. Magnetic resonance imaging (MRI) of the lumbar spine was performed before treatment and at 8-year follow-up. ADD was categorized as increased or not increased based on an evaluation of Modic changes, disc height reduction, disc contour, herniation size, nucleus pulposus signal, and posterior high intensity zones. We used a chi test or a Fisher exact test to compare crude proportions, and multiple linear regressions to analyze the association between increased ADD (yes/no) and change in Oswestry Disability Index (ODI) from pre-treatment to follow-up. RESULTS: ADD increased (for at least one ADD variable) in 23 of 57 patients (40%) treated nonoperatively, and 29 of 69 patients (42%) treated with TDR (P = 0.86). We found no significant associations between ADD increase and the change in ODI. CONCLUSION: Increased ADD occurred with similar frequency after TDR and after nonoperative treatment, and was not related to the clinical outcome at 8-year follow-up. LEVEL OF EVIDENCE: 1. PMID- 29794584 TI - Efficacy and Safety of Full-endoscopic Decompression via Interlaminar Approach for Central or Lateral Recess Spinal Stenosis of the Lumbar Spine: A Meta analysis. AB - STUDY DESIGN: A meta-analysis of five retrospective cohort studies. OBJECTIVE: The aim of the study was to delineate the efficacy and safety of full-endoscopic decompression via the interlaminar approach for central or lateral recess spinal stenosis of the lumbar spine using a meta-analysis. SUMMARY OF BACKGROUND DATA: The paradigm of spinal endoscopy is shifting from treatment of soft disc herniation to that of lumbar spinal stenosis. Technical advancements have enabled full-endoscopic decompression in spinal stenosis surgery. There is few strong evidence supporting this surgical technique, and clinicians usually rely on their own opinions and experiences. METHODS: A systematic search of electronic databases, including PubMed, EMBASE, Cochrane Library, Web of science, and KoreaMed, up to August 2017 was performed to identify studies concerning full endoscopic decompression via the interlaminar approach for lumbar spinal stenosis. Changes in clinical outcomes [Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain] were compared with the minimal clinically important difference (MCID) for each item. We then calculated the mean differences and 95% confidence intervals (95% CIs) using random-effects models. RESULTS: We included data from five studies involving 156 patients at 6- and 12 month follow-ups. The majority of enrolled papers included patients with neurogenic claudication due to central stenosis refractory to conservative management and excluded patients with significant instability or previous surgery. The overall mean difference of patients with ODI and VAS scores for leg and back pain exceeded the criteria for MCID. ODI scores improved by 41.71 (95% CI, 39.80-43.62) after the surgery, which was twice the MCID. The VAS leg and back pain scores improved by 5.95 (95% CI, 5.70-6.21) and 4.22 (95% CI, 3.88 4.56), respectively, indicating statistically significant improvement over the MCID. CONCLUSION: Successful clinical outcomes can be achieved with full endoscopic decompression via the interlaminar approach for lumbar central spinal stenosis in patients for the defined indications. LEVEL OF EVIDENCE: 2. PMID- 29794585 TI - Imaging Comparison Between Chinese and Japanese Patients With Cervical Ossification of the Posterior Longitudinal Ligament. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: To identify the radiographic differences between Chinese and Japanese patients with cervical ossification of the posterior longitudinal ligament (OPLL) using computed tomography (CT) and magnetic resonance imaging (MRI), and to compare the characteristics of OPLL between the two nationalities. SUMMARY OF BACKGROUND DATA: OPLL has a high prevalence in East Asia. However, the differences between Chinese and Japanese OPLL patients are poorly known. METHODS: This was a retrospective study of Chinese (n = 300) and Japanese (n = 102) consecutive patients who received a diagnosis of cervical OPLL between January 2010 and December 2014. All patients underwent CT and MRI. The type and distribution of OPLL were determined. Spinal compression was assessed by MRI. OPLL type, distribution, comorbidity, and compression of the spinal cord were examined. The ossification index (OP-index) was used to evaluate the OPLL. Factors contributing to the OP-index were examined by multivariate analysis. RESULTS: The Chinese patients were younger than the Japanese patients (P < 0.0001), and there were more women among the Chinese patients (P = 0.0002). The OP-index was higher among the Japanese patients (median, 5 vs. 4, P = 0.003). Among men, OPLL lesions were more frequent in the under 55-year-old Japanese at C7 (P = 0.04), in the 55 to 64-year-old Japanese at C4, C5, and C6 (all P < 0.05), and in the over 64-year-old Japanese at C3/4 (P = 0.01), compared with their Chinese counterparts. Among women, OPLL lesions were more frequent in the 55 to 64-year-old Japanese at C6 (P = 0.04). The multivariate analysis showed that only age was independently associated with the OP-index (odds ratio [OR] = 1.023, 95% confidence interval [CI]: 1.002-1.045, P = 0.034). CONCLUSION: Japanese patients had a higher frequency of OPLL lesions at C5, C6, and C7. Age was independently associated with OPLL. LEVEL OF EVIDENCE: 3. PMID- 29794586 TI - Evidence-based Care Bundles for Preventing Surgical Site Infections in Spinal Instrumentation Surgery. AB - STUDY DESIGN: A retrospective study, using prospectively collected data. OBJECTIVE: The aim of this study was to evaluate the impact of evidence-based care bundles for preventing surgical site infections (SSIs) in spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: About half of all SSIs are preventable via evidence-based methods. For successful SSI prevention, the bacterial load must be minimized, and methicillin-resistant Staphylococcus aureus (MRSA) protection must be maximized. However, it is difficult to cover all of these requirements by single preventative method. METHODS: We screened consecutive patients scheduled for spinal instrumentation surgeries at a single tertiary referral hospital for high surgical, SSI, and MRSA colonization risks. Evidence-based care bundles were implemented for high-risk patients and included 1) additional vancomycin prophylaxis, 2) diluted povidone-iodine irrigation, and 3) nasal and body decontamination. Patient demographics, comorbidities, operative features, and SSIs reported to the Japanese Nosocomial Infections Surveillance system were prospectively obtained in the same method by the same assessor and were used for the analyses. The results were compared before and after the application of the bundle. RESULTS: There were 1042 spinal instrumentation surgeries (741 before and 301 after care bundles) performed from November 2010 to December 2015. Of 301 surgeries, 57 cases (18.9%) received care bundles. There were no significant differences in patient backgrounds before and after the intervention. The SSI rate decreased significantly from 3.8% to 0.7% (P < 0.01) after the intervention, with an overall 82% relative risk reduction. A significant protective effect was observed in the multivariate analysis (adjusted odds ratio 0.18, 95% confidence interval: 0.04-0.77, P = 0.02). There were no MRSA-related SSIs among those that received care bundles, even though MRSA was the predominant pathogen in the study population. CONCLUSION: Evidence-based care bundles, applied in selected high-risk spinal instrumentation cases, minimized bacterial load, maximized MRSA protection, and significantly reduced SSI rates without topical vancomycin powder. LEVEL OF EVIDENCE: 4. PMID- 29794587 TI - Opioid Dependence and Prolonged Length of Stay in Lumbar Fusion: A Retrospective Study Utilizing the National Inpatient Sample 2003-2014. AB - STUDY DESIGN: Retrospective cohort utilizing the National Inpatient Sample (NIS) 2003 to 2014. OBJECTIVE: To investigate the association of opioid dependence with prolonged length of stay (LOS), costs, and surgical complications in elective one to-two level lumbar fusion. SUMMARY OF BACKGROUND DATA: Opioids are the most commonly prescribed drug class to treat back pain. Few studies have examined the impact of opioid dependence on spinal fusion outcomes. The data available show inconsistent conclusions regarding the association between opioid dependence and LOS. METHODS: Data from 1,826,868 adult elective one-to-two level lumbar fusion discharges in the NIS from 2003 to 2014 were included. Discharges were categorized into an opioid-dependent or unaffected cohort based on the presence or absence of an International Classification of Disease, Ninth Revision-Clinical Modification (ICD-9-CM) code for opioid dependence. Incidence of opioid dependence was compared between 2003 and 2014 via adjusted Wald tests. Patient and surgical characteristics, costs, and complications were compared between cohorts via chi-square tests or adjusted Wald tests for categorical and continuous variables, respectively. Patient and surgical factors were tested for association with prolonged LOS via univariable logistic regressions, and significant (P <= 0.01) factors were included in a multivariable logistic regression. RESULTS: Seven thousand nine hundred sixty-four (0.44%) discharges included a diagnosis of opioid dependence. The incidence of opioid dependence increased from 2003 to 2014. Opioid dependence was associated with an adjusted 2.11 times higher odds of prolonged LOS. Opioid-dependent discharges accrued higher costs and had higher frequencies of infection, device-related complications, hematoma- or seroma-related complications, acute posthemorrhagic anemia, and pulmonary insufficiency. CONCLUSION: This nationally-representative study suggests that opioid dependence is associated with prolonged LOS in lumbar fusion, as well as higher costs and higher frequencies of surgical complications. Further investigations are needed to determine the optimal method to treat opioid dependent patients who require lumbar fusion. LEVEL OF EVIDENCE: 3. PMID- 29794588 TI - Clinical Impact and Economic Burden of Hospital-Acquired Conditions Following Common Surgical Procedures. AB - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To assess the clinical impact and economic burden of the three most common hospital acquired conditions (HACs) that occur within 30-day postoperatively for all spine surgeries and to compare these rates with other common surgical procedures. SUMMARY OF BACKGROUND DATA: HACs are part of a non-payment policy by the Centers for Medicare and Medicaid Services and thus prompt hospitals to improve patient outcomes and safety. METHODS: Patients more than 18 years who underwent elective spine surgery were identified in American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2013. Primary outcomes were cost associated with the occurrence of three most common HACs. Cost associated with HAC occurrence derived from the PearlDiver database. RESULTS: Ninety thousand five hundred fifty one elective spine surgery patients were identified, where 3021 (3.3%) developed at least one HAC. Surgical site infection (SSI) was the most common HAC (1.4%), then urinary tract infection (UTI) (1.3%) and venous thromboembolism (VTE) (0.8%). Length of stay (LOS) was longer for patients who experienced a HAC (5.1 vs. 3.2 d, P < 0.001). When adjusted for age, sex, and Charlson Comorbidity Index, LOS was 1.48 +/- 0.04 days longer (P < 0.001) and payments were $8893 +/- $148 greater (P < 0.001) for patients with at least one HAC. With the exception of craniotomy, patients undergoing common procedures with HAC had increased LOS and higher payments (P < 0.001). Adjusted additional LOS was 0.44 +/- 0.02 and 0.38 +/- 0.03 days for total knee arthroplasty and total hip arthroplasty, and payments were $1974 and $1882 greater. HACs following hip fracture repair were associated with 1.30 +/- 0.11 days LOS and $4842 in payments (P < 0.001). Compared with elective spine surgery, only bariatric and cardiothoracic surgery demonstrated greater adjusted additional payments for patients with at least one HAC ($9975 and $10,868, respectively). CONCLUSION: HACs in elective spine surgery are associated with a substantial cost burden to the health care system. When adjusted for demographic factors and comorbidities, average LOS is 1.48 days longer and episode payments are $8893 greater for patients who experience at least one HAC compared with those who do not. LEVEL OF EVIDENCE: 3. PMID- 29794589 TI - Course and Contributors to Back Pain in Middle-aged Women Over 9 Years: Data From the Australian Longitudinal Study on Women's Health. AB - STUDY DESIGN: Community-based, cohort study. OBJECTIVE: Our aim was to determine the course of back pain in middle-aged women over a 9-year period, and assess whether obesity and physical inactivity are associated with more frequent back pain. SUMMARY OF BACKGROUND DATA: Back pain is the leading cause of disability worldwide. With minimal effective therapies and rising financial burden, identifying modifiable risk factors remains a key priority. METHODS: The Australian Longitudinal Study on Women's Health is a cohort study of community based, middle-aged women who completed questionnaires every 3 years between 2004 and 2013. Approximately, 10,530 women completed the survey in 2004 (mean age 55.5 yrs), and 9020 completed follow-up 9 years later. Self-reported data on back pain in the last 12 months and other sociodemographic factors were collected at all four surveys. 'Frequent back pain' was defined as back pain reported at >= three surveys. RESULTS: Back pain was common and persistent, with 48% having back pain in >= three out of four surveys. Baseline obesity (relative risk [RR] 1.18, 95% confidence interval [CI] 1.12-1.25), lack of vigorous physical activity (RR 1.17, 95% CI 1.10-1.25), depressive symptoms (RR 1.40, 95% CI 1.33-1.47), and low education status (RR 1.17, 95% CI 1.12-1.24), were independently associated with an increased risk of frequent back pain (all P < 0.001). Overall, 28% of the risk of frequent back pain could be attributed to these factors, equating to one extra case of frequent back pain for every five women with depressive symptoms, for every 11 obese women, for every 12 women with low-education status, and for every 13 women who do not do vigorous physical activity, at baseline. CONCLUSION: Obesity, depressive symptoms, low-education status, and lack of vigorous physical activity are associated with higher risk of frequent back pain over the following 9 years among women in their mid-50 s. Targeting these risk factors may lessen the burden of back pain. LEVEL OF EVIDENCE: 2. PMID- 29794590 TI - Radiological Evaluation of Craniocervical Region in Patients with Basilar Invagination. AB - STUDY DESIGN: A retrospective analysis of collected data. OBJECTIVE: Our study aims to present the morphology of cranial-cervical spinal canal in basilar invagination (BI) patients. SUMMARY OF BACKGROUND DATA: BI is characterized by protrusion of the odontoid process into the foramen magnum (C0), leading to compression of the cervicomedullary junction. However, no study has ever clarified the anatomical diameters of spinal canal in patients with BI. METHODS: The study retrospectively examined computed tomography (CT)-based anatomical characteristics in a cohort of 84 patients with and without BI. We measured the anteroposterior diameter (APD) and transversal diameter (TVD) of spinal canal from C0 to C4, together with the area of vertebral canal (Area). Independent samples t test was used for statistical analysis. RESULTS: The APD in the BI group was shorter than the control group from C0 to C2 (C0: 27.98 vs. 35.11 mm, P < 0.001; C1: 11.87 vs. 16.91 mm, P < 0.001; C2: 12.91 vs. 14.84 mm, P < 0.001), but it became longer from C3 to C4. The TVD of the BI group was significantly wider from C0 to C3 (C0: 30.59 vs. 28.54 mm, P < 0.001; C1: 31.31 vs. 25.98 mm, P < 0.001; C2: 21.56 vs. 20.40 mm, P = 0.01; C3: 22.45 vs. 21.23 mm, P = 0.013), and it had no significance at C4. The Area showed no difference between the two groups from C1 to C2, but it turned larger at C3 and C4 in BI patients. CONCLUSION: BI patients may have shorter APD from C0 to C2, which could be the leading cause of neurological compression, necessitating decompression on sagittal plane. Below the pathological levels, BI patients have larger spinal canal than general population. LEVEL OF EVIDENCE: 3. PMID- 29794591 TI - Here Comes Price Transparency. AB - The public reporting of clinical and operational performance measures is old news for chief nurse executives (CNEs). Since the advent of value-based purchasing and patient experience measures, CNEs have partnered with other executives to ensure organizational readiness and success with the performance measures being publicly shared. In 2018, healthcare organizations face a new wave of public reporting expectations-price. Once again, executives will need to ensure organizational readiness. Chief nurse executives must analyze the impact of this trend on the nursing enterprise and carefully consider how to best prepare for healthcare price transparency. PMID- 29794592 TI - Advanced Resuscitation Guidelines Improve Mortality Rates Among Cardiovascular Surgery Patients. AB - In this month's Magnet(r) Perspectives column, Melanie Roberts, DNP, RN-BC, CNS, CCNS, CCRN, critical care clinical nurse specialist at Medical Center of the Rockies (MCR) and Poudre Valley Hospital, discusses her efforts to implement the state-ofthe-art European Resuscitation Council (ERC) guideline for resuscitation of cardiovascular (CV) surgery patients. Her evidence-based initiative has improved quality of care and mortality rates among the CV surgery population at MCR. Dr Roberts' pioneering work earned her the 2017 National Magnet Nurse of the Year Award for Empirical Outcomes. She shares details of her innovative program and examines the value of implementing practice enhancements in a Magnet environment. She describes the importance of an interdisciplinary team effort to achieve success. PMID- 29794593 TI - Leadership, Longevity, and Leaning In: An Interview With Mary Jo (Joey) Bulfin. AB - This column profiles Mary Jo Bulfin, MBA, RN, CENP, chief executive officer of St. Mary's Medical Center, West Palm Beach, Florida. Ms Bulfin began her career as a staff nurse in the organization where she is now the CEO and discusses her career path and lessons learned. PMID- 29794594 TI - A Hospital-Based Neuroscience Nursing Course Designed to Improve Competence and Confidence. AB - After experiencing growth in a neuroscience service line, nurse leaders identified a need for increased competencies among clinical staff. This hospital met the need by developing a unique multidisciplinary neuroscience nursing course to improve the clinical competence, confidence, and professional development of bedside nurses. PMID- 29794595 TI - Assessing the Degree of Compassion Satisfaction and Compassion Fatigue Among Critical Care, Oncology, and Charge Nurses. AB - OBJECTIVES: The aim of this study was to assess the degree of compassion satisfaction and compassion fatigue (CF) among critical care, oncology and charge nurses. BACKGROUND: Cumulative grief resulting from caring for critically/terminally ill patients may result in CF, leading to lower quality care and higher nurse attrition. METHOD: Data were collected from 38 direct care nurses and 10 charge nurses, using the Professional Quality of Life. RESULTS: Charge nurses had higher secondary traumatic stress (STS) than direct care nurses. Nurses with less than 10 years of experience had lower CS than experienced nurses. Higher levels of burnout (BO) and STS were reported among charge nurses, whereas less direct care nurses had average to high BO and STS ratings. CONCLUSIONS: Previous studies focused on direct care nurses; our findings suggest that CF is prevalent among charge nurses as well. Interventions should be considered for clinical providers and charge nurses including debriefing, stress reduction, peer support, and team building. PMID- 29794596 TI - Keeping the Magnet(r) Flame Alive With Appreciative Inquiry. AB - Sustaining a clinical excellence culture for Magnet(r) redesignation requires continued engagement of frontline nurses, nurse leaders, and executives. Appreciative Inquiry is a strength-based approach emanating from a positive core. From this core, teams discover, dream, design, and create their preferred destiny. This article describes how a Magnet-designated organization used Appreciative Inquiry to revitalize its redesignation preparation and beyond. PMID- 29794597 TI - Top-of-License Nursing Practice, Part 2: Differentiating BSN and ADN Perceptions of Top-of-License Activities. AB - OBJECTIVE: The aim of this study was to describe differences in associate degree (ADN) and baccalaureate degree-prepared (BSN) nurses' perceptions of top-of license (TOL) practice. BACKGROUND: To date, no empirical work has examined whether ADN and BSN nurses approach TOL practice nursing activities differently. METHODS: We conducted a qualitative pilot study with focus groups to explore the perceptions of a group of ADN- and BSN-prepared nurses concerning nursing activities and their relation to TOL practice. RESULTS: Subthemes emerged differentiating how ADN and BSN nurses perceived their responsibilities related to critical thinking, communication, and patient education. For professional nursing care, 5 subthemes further emerged: (a) approaches to assessment, (b) chart review, (c) psychosocial patient care, (d) documentation, and (e) handoff. CONCLUSIONS: The differences identified in approaches to TOL practice activities by educational preparation have implications for staffing patterns that can optimize the contribution of ADN- and BSN-prepared nurses. Further research is indicated. PMID- 29794598 TI - Do Health Promotion Behaviors Affect Levels of Job Satisfaction and Job Stress for Nurses in an Acute Care Hospital? AB - OBJECTIVE: The aim of this study was to explore the relationships between nurse reported health-promoting behaviors (HPBs), job stress, and job satisfaction in a hospital setting. BACKGROUND: Job stress and satisfaction are key components of the nursing work environment; however, evidence of the relationship between HPB and job stress and satisfaction is lacking. METHODS: A cross-sectional, 144-item survey was administered to nurses working in an acute care, community hospital in the southeastern United States. RESULTS: Higher levels of HPB were associated with lower job stress and higher job satisfaction. Total HPB was associated with the competence subscale of job stress. Lower job stress was significantly associated with HPB subscales: spiritual growth, interpersonal relations, and stress management. CONCLUSIONS: Nursing organizations can implement interventions that support HPB for nurses to reduce job stress and improve satisfaction. PMID- 29794599 TI - Using Motivational Interviewing to Impact Readiness of RNs to Return to the Classroom. AB - Supporting nurses with associate degrees in nursing (ADNs) to return to school is challenging for nurse executives. Strategies include tuition reimbursement, scholarships, and flexible scheduling. Despite these measures, it is anticipated that we will fall short of a goal of 80% bachelor's degree-prepared nurses by 2020. The aim of this project was to increase ADN-prepared RN readiness to return to school through motivational interviewing. PMID- 29794600 TI - HIV prevalence and sexual behavior among young male conscripts in the Brazilian army, 2016. AB - Since 1996, the Brazilian Department of Sexually Transmitted Infections (STI), AIDS and Viral Hepatitis (Departamento de Vigilancia, Prevencao e Controle das IST, do HIV, AIDS e Hepatites Virais, Secretaria de Vigilancia em Saude, Ministerio da Saude) in collaboration with the Brazilian Ministry of Defense has conducted periodic and anonymous probability sample surveys to determine the human immunodeficiency virus (HIV) prevalence, the sexual and risk behaviors among conscripts of the Brazilian army. This study aimed to estimate the HIV seroprevalence of conscripts in Brazil by geographic region and to describe behavior in relation to the risk of HIV transmission by analyzing data from the Brazilian Conscripts Survey 8th edition performed in 2016.Conscripts were selected with a 2-stage sampling method stratified by geographical region. The study included a self-reported questionnaire and blood collection for HIV, hepatitis, and syphilis testing. Data from 37,282 conscripts between 17 and 22 years of age were analyzed. Of these conscripts, 73.7% stated that they were sexually active. The overall country-wide prevalence of HIV was 0.12%. The geographic prevalence rates were as follows: north (0.24%), northeast (0.15%), central-west (0.13%), southeast (0.07%), and south (0.10%). The proportion of conscripts who reported having sex with other men was 4.4%, and the estimated HIV prevalence in this group was 1.32%. Regarding prophylaxis use, 45.6% of the participants reported consistent condom use with casual partners within the last year, and 34.5% reported condom use with steady partners within the last year. The independent factors associated with HIV infection were: MSM status (odds ratio [OR] = 14.62; P = .000) and having more than 10 partners over their lifetime (OR = 3.32; P = .028).Our data suggest that the HIV prevalence among young men in Brazil remains stable except for the north region, and MSM continue to be associated with a high risk for HIV infection at a rate that is approximately 13-fold higher than the rate among men without a history of sex with another man. Our findings confirm the need to scale up combination HIV prevention for young men, including MSM, in Brazil. PMID- 29794602 TI - Presenting national HIV/AIDS and sexually transmitted disease research in Brazil. PMID- 29794601 TI - HIV, HCV, HBV, and syphilis among transgender women from Brazil: Assessing different methods to adjust infection rates of a hard-to-reach, sparse population. AB - Different sampling strategies, analytic alternatives, and estimators have been proposed to better assess the characteristics of different hard-to-reach populations and their respective infection rates (as well as their sociodemographic characteristics, associated harms, and needs) in the context of studies based on respondent-driven sampling (RDS). Despite several methodological advances and hundreds of empirical studies implemented worldwide, some inchoate findings and methodological challenges remain. The in-depth assessment of the local structure of networks and the performance of the available estimators are particularly relevant when the target populations are sparse and highly stigmatized. In such populations, bottlenecks as well as other sources of biases (for instance, due to homophily and/or too sparse or fragmented groups of individuals) may be frequent, affecting the estimates.In the present study, data were derived from a cross-sectional, multicity RDS study, carried out in 12 Brazilian cities with transgender women (TGW). Overall, infection rates for HIV and syphilis were very high, with some variation between different cities. Notwithstanding, findings are of great concern, considering the fact that female TGW are not only very hard-to-reach but also face deeply-entrenched prejudice and have been out of the reach of most therapeutic and preventive programs and projects.We cross-compared findings adjusted using 2 estimators (the classic estimator usually known as estimator II, originally proposed by Volz and Heckathorn) and a brand new strategy to adjust data generated by RDS, partially based on Bayesian statistics, called for the sake of this paper, the RDS-B estimator. Adjusted prevalence was cross-compared with estimates generated by non weighted analyses, using what has been called by us a naive estimator or rough estimates. PMID- 29794603 TI - External quality assessment for CD4 + T-lymphocyte count test: Performance of the Brazilian public health laboratories network. AB - The National Network for CD4+ T-lymphocyte counting of Brazil comprises 93 laboratories. This study reports the laboratory performances achieved in external quality assessment (EQA) rounds provides by Ministry of Health to evaluate the quality of the kits used and the performance of test by the technicians.Ten EQA rounds were analyzed according the EQA criteria aimed to evaluate individual laboratory performance on the basis of the accuracy of their results compared to the general mean obtained by all participating laboratories and the reproducibility of the results obtained between 2 samples from the same donor.The percentage of approved and failed laboratories in the EQAs tends to follow a uniform pattern. Since 2011, approval has remained above 80% and the failure rate has never exceeded 15%.EQA is very important to evaluate the performance of the laboratories, to identify monitor, and to resolve errors as quickly as possible. PMID- 29794606 TI - Reaching Out. PMID- 29794605 TI - PrEP adopted by the brazilian national health system: What is the size of the demand? AB - BACKGROUND: Brazil's response to the HIV epidemic now includes free access to preexposure prophylaxis (PrEP) to populations at substantial risk for HIV infection including men who have sex with men (MSM). We used nationally representative demographic, epidemiologic, and surveillance data to offer estimates for the number of MSM at substantial risk for HIV infection who might be eligible and willing to use PrEP in Brazil. METHODS: Starting from the age/sex stratified population, we calculated the number of men aged 15 to 64 years, in 5 year age groups, and the proportion of those who report sex with other men during their lifetime. We focused on 11 cities (representing all regions) that are responsible for a significant fraction of the HIV burden of the country and used city-specific HIV prevalence estimates to infer the fraction of MSM who are HIV negative. We then derived the proportion of HIV-negative MSM under substantial risk for HIV infection defined as having unprotected receptive anal intercourse in the 6 months before study participation. Finally, PrEP uptake among the eligible was inferred from the PrEP Brazil study. RESULTS: Our results show that PrEP demand in these 11 cities is of 66,120 men aged 15 to 64 years. When we consider the lower and upper bounds for the available parameters, we find that PrEP demand in these 11 cities might vary from 33,378 to 97,962 men. If PrEP is restricted to those aged 15 to 49 years, demand drops by 20%. PrEP demand varies considerably by city, mostly because of the differences in population size and city-specific HIV prevalence. DISCUSSION: We have shed light on the probable size of PrEP demand in Brazil certain that the incorporation of PrEP as part of Brazil's combination prevention for populations at substantial risk for HIV infection is a necessary challenge. PrEP will not only prevent HIV infections, it will also expand testing among the most vulnerable with the added benefit of offering combination prevention for the uninfected and immediate treatment for those already infected. As such, expected added benefits of PrEP will be earlier linkage to care, prompt treatment initiation leading to health benefits and decreased transmission. PMID- 29794607 TI - Considerations for Incision and Flap Design With Implant Therapy in the Esthetic Zone. AB - The planning and design of any incision in the esthetic zone should be carried out based on biologic principles and with careful consideration of the desired esthetic outcome. Different incision and flap designs have been identified for implant and implant-related surgeries in the esthetic zone. Those include; flapless, vestibular incision, papilla sparing, envelope, triangular, and trapezoidal. The specific aim of this article is to outline various important factors that influence healing, to discuss the advantages/disadvantages of several key incision/flap designs, and to help guide the clinician in treatment planning tooth replacement in the esthetic zone. PMID- 29794608 TI - Effects of Osteotomy Lengths on the Temperature Rise of the Crestal Bone During Implant Site Preparation: Erratum. PMID- 29794604 TI - HIV prevalence among men who have sex with men in Brazil: results of the 2nd national survey using respondent-driven sampling. AB - This paper reports human immuno-deficiency virus (HIV) prevalence in the 2nd National Biological and Behavioral Surveillance Survey (BBSS) among men who have sex with men (MSM) in 12 cities in Brazil using respondent-driven sampling (RDS).Following formative research, RDS was applied in 12 cities in the 5 macroregions of Brazil between June and December 2016 to recruit MSM for BBSS. The target sample size was 350 per city. Five to 6 seeds were initially selected to initiate recruitment and coupons and interviews were managed online. On-site rapid testing was used for HIV screening, and confirmed by a 2nd test. Participants were weighted using Gile estimator. Data from all 12 cities were merged and analyzed with Stata 14.0 complex survey data analysis tools in which each city was treated as its own strata. Missing data for those who did not test were imputed HIV+ if they reported testing positive before and were taking antiretroviral therapy.A total of 4176 men were recruited in the 12 cities. The average time to completion was 10.2 weeks. The longest chain length varied from 8 to 21 waves. The sample size was achieved in all but 2 cities.A total of 3958 of the 4176 respondents agreed to test for HIV (90.2%). For results without imputation, 17.5% (95%CI: 14.7-20.7) of our sample was HIV positive. With imputation, 18.4% (95%CI: 15.4-21.7) were seropositive.HIV prevalence increased beyond expectations from the results of the 2009 survey (12.1%; 95%CI: 10.0-14.5) to 18.4%; CI95%: 15.4 to 21.7 in 2016. This increase accompanies Brazil's focus on the treatment to prevention strategy, and a decrease in support for community based organizations and community prevention programs. PMID- 29794609 TI - Effects of internet-based pain coping skills training before home exercise for individuals with hip osteoarthritis (HOPE trial): a randomised controlled trial. AB - This assessor-, therapist-, and participant-blinded randomised controlled trial evaluated the effects of an automated internet-based pain coping skills training (PCST) program before home exercise for people with clinically diagnosed hip osteoarthritis. One hundred forty-four people were randomised to either the PCST group or the comparator group. In the first 8 weeks, the PCST group received online education and PCST, whereas the comparison group received online education only. From weeks 8 to 24, both groups visited a physiotherapist 5 times for home exercise prescription. Assessments were performed at baseline, 8, 24, and 52 weeks. Primary outcomes were hip pain on walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) at 24 weeks. Secondary outcomes were other measures of pain, quality-of-life, global change, self-efficacy, pain coping, pain catastrophizing, depression, anxiety, stress, physical activity, and adverse events. Primary outcomes were completed by 137 (95%), 131 (91%), and 127 (88%) participants at 8, 24, and 52 weeks, respectively. There were no significant between-group differences in primary outcomes at week 24 (change in: walking pain [mean difference 0.5 units; 95% confidence interval, -0.3 to 1.3] and function [ 0.9 units; 95% confidence interval, -4.8 to 2.9]), with both groups showing clinically relevant improvements. At week 8, the PCST group had greater improvements in function, pain coping, and global improvement than comparison. Greater pain coping improvements persisted at 24 and 52 weeks. In summary, online PCST immediately improved pain coping and function but did not confer additional benefits to a subsequent exercise program, despite sustained pain coping improvements. PMID- 29794610 TI - Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis. AB - In knee osteoarthritis (OA), pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of pain sensitization and clinical outcome (nonresponse) after guideline-based physiotherapy in people with knee OA. Participants (n = 156) with moderate/severe knee OA were recruited from secondary care. All participants completed self administered questionnaires and underwent quantitative sensory testing at baseline, thereby establishing subjective and objective measures of pain sensitization. Participants (n = 134) were later classified after a physiotherapy intervention, using treatment responder criteria (responder/nonresponder). Quantitative sensory testing data were reduced to a core set of latent variables using principal component analysis. A hierarchical logistic regression model was constructed to investigate whether features related to pain sensitization predicted nonresponse after controlling for other known predictors of poor outcome in knee OA. Higher temporal summation (odds ratio 2.00, 95% confidence interval 1.23-3.27) and lower pressure pain thresholds (odds ratio 0.48, 95% confidence interval 0.29-0.81) emerged as robust predictors of nonresponse after physiotherapy, along with a higher comorbidity score. The model demonstrated high sensitivity (87.8%) but modest specificity (52.3%). The independent relationship between pain sensitization and nonresponse may indicate an underlying explanatory association between neuroplastic changes in nociceptive processing and the maintenance of ongoing pain and disability in knee OA pain. These preliminary results suggest that interventions targeting pain sensitization may warrant future investigation in this population. PMID- 29794612 TI - Delayed onset of persistent discogenic axial and radiating pain after a single level lumbar intervertebral disc injury in mice. AB - Low back pain (LBP) is associated with both axial discomfort and radiating leg pain. Although intervertebral discs are suspected as the source of pain in some individuals, the relationship between disc degeneration and back pain remains controversial. The goals of this study were to investigate the long-term impact of L4/L5 disc puncture on disc degeneration and the subsequent emergence, persistence, and underlying mechanisms of axial and radiating LBP in mice. L4 to L5 discs were punctured on the ventral aspect with a 30 gauge needle in 3-month old female CD1 mice, and the development of behavioral signs of axial discomfort (tail suspension and grip force), radiating hypersensitivity (von Frey and acetone), and motor impairment (rotarod) were monitored. Disc degeneration was assessed using X-ray, T2-magnetic resonance imaging, and histology, and persisted for up to 1 year. Innervation was quantified by immunohistochemistry using the pan-neuronal marker PGP9.5. Behavioural signs of axial discomfort peaked 3 to 9 months after injury. During the peak, local nerve density was increased. A transient increase in hypersensitivity to cold, suggestive of radiating pain, was observed 2 weeks after injury. Radiating pain then reemerged 9 to 12 months after injury in half the animals and correlated with increased dorsal innervation and reduced disc height at these late time points. In summary, a single-level disc injury is sufficient to induce prolonged disc degeneration and delayed axial and radiating pain. This model will be useful to investigate underlying mechanisms and potential therapeutic strategies for discogenic LBP. PMID- 29794611 TI - Racial differences in opioid prescribing for children in the United States. AB - Racial differences exist in analgesic prescribing for children during emergency department and ambulatory surgery visits in the United States; however, it is unknown whether this is true in the outpatient setting. We examined racial and ethnic differences in outpatient analgesic prescribing using nationally representative data from 113,929 children from the Medical Expenditure Panel Survey. We also examined whether patient-provider race and ethnic concordance was associated with opioid prescription. White children were more commonly prescribed opioids as compared to minorities (3.0% vs 0.9%-1.7%), except for Native American children who had similar rates of opioid prescription (2.6%) as white children. Minorities were more likely to receive nonopioid analgesics than white children (2.0%-5.7% vs 1.3%). Although most white children had race-concordant providers (93.5%), only 34.3% of black children and 42.7% of Hispanic children had race concordant providers. Among black children, having a race concordant usual source of care provider was associated with a decreased likelihood of receiving an opioid prescription as compared to having a white usual source of care provider (adjusted odds ratio [95% confidence interval] = 0.51 [0.30-0.87]). For all other racial groups, patient-provider race-concordance was not associated with likelihood of opioid prescription. Racial differences exist in analgesic prescriptions to children at outpatient health care visits in the United States, with white children more likely to receive opioids and minorities more likely to receive nonopioid analgesics. Health care providers' race and ethnicity may play a significant role in extant analgesic differences. Further work should focus on understanding the role of provider race and ethnicity in analgesic differences to children in the United States. PMID- 29794613 TI - What do clinicians consider when assessing chronic low back pain? A content analysis of multidisciplinary pain centre team assessments of functioning, disability, and health. AB - Beyond expert suggestions as to the appropriate subject matter for chronic pain assessments, little is known about the actual content of multidisciplinary pain centre (MPC) clinical assessments. The International Classification of Functioning, Disability and Health Low Back Pain Core Set (ICF LBP-CS) provides a universal language to support the consistent description of LBP-related assessments across disciplines within multidisciplinary teams (MDTs). This study sought to map the content of MPC clinical assessments to the ICF to: (1) identify and compare the content of clinical MDT assessments using a cross-disciplinary framework and (2) examine the content validity of the LBP-CS. A qualitative examination of MPC team clinical assessments of chronic low back pain was undertaken. Multidisciplinary team (pain medicine, psychiatry, nursing, physiotherapy, occupational therapy, and psychology) assessments were audio recorded and transcribed. Concepts were extracted from transcripts using a meaning condensation procedure and then linked to the ICF. Across 7 MDT assessments, comprised 42 discipline-specific assessments and 241,209 transcribed words, 8596 concepts were extracted. Contextual factors (ie, the person and environment), except for physiotherapy, accounted for almost half of each discipline's assessments (range: 49%-58%). Concepts spanned 113 second-level ICF categories, including 73/78 LBP-CS categories. Overall, the findings revealed novel insights into the content of MPC clinical assessments that can be used to improve health care delivery. International Classification of Functioning, Disability and Health-based assessment profiles demonstrated unique contributions from each discipline to chronic low back pain assessment. Finally, users of the LBP-CS can be confident that the tool exhibits sound content validity from the perceptive of MDT assessments of functioning, disability, and health. PMID- 29794614 TI - Chronic neuropathic pain reduces opioid receptor availability with associated anhedonia in rat. AB - The opioid system plays a critical role in both the experience and management of pain. Although acute activation of the opioid system can lead to pain relief, the effects of chronic pain on the opioid system remain opaque. Cross-sectional positron emission tomography (PET) studies show reduced availability of brain opioid receptors in patients with chronic pain but are unable to (1) determine whether these changes are due to the chronic pain itself or due to preexisting or medication-induced differences in the endogenous opioid system, and (2) identify the neurobiological substrate of reduced opioid receptor availability. We investigated these possibilities using a well-controlled longitudinal study design in rat. Using [F]-FDPN-PET in either sham rats (n = 17) or spared nerve injury rats (n = 17), we confirmed reduced opioid receptor availability in the insula, caudate-putamen, and motor cortex of nerve injured rats 3 months after surgery, indicating that painful neuropathy altered the endogenous opioid system. Immunohistochemistry showed reduced expression of the mu-opioid receptor, MOR1, in the caudate-putamen and insula. Neither the opioid peptide enkephalin nor the neuronal marker NeuN differed between groups. In nerve-injured animals, sucrose preference, a measure of anhedonia/depression-like behavior, positively correlated with PET opioid receptor availability and MOR1-immunoreactivity in the caudate-putamen. These findings provide new evidence that the altered supraspinal opioid receptor availability observed in human patients with chronic pain may be a direct result of chronic pain. Moreover, reduced opioid receptor availability seems to reflect decreased receptor expression, which may contribute to pain induced depression. PMID- 29794615 TI - Chronic pain and opioid receptor availability: disentangling the molecular contributions and the "chicken or the egg" dilemma. PMID- 29794617 TI - Editor's Note: Congratulations to the 2018 Author and Reviewer Award Winners. PMID- 29794616 TI - Dynamic Preictal Discharges in Patients With Mesial Temporal Lobe Epilepsy. AB - PURPOSE: It has been challenging to detect early changes preceding seizure onset in patients with epilepsy. This study investigated the preictal discharges (PIDs) by intracranial electroencephalogram of 11 seizures from 7 patients with mesial temporal lobe epilepsy. METHODS: The EEG segments consisting of 30 seconds before ictal onset and 5 seconds after ictal onset were selected for analysis. After PID detection, the amplitude and interval were measured. According to the timing of PID onset, the 30-second period preceding seizure onset was divided into two stages: before PID stage and PID stage. The autocorrelation coefficients during the two stages were calculated and compared. RESULTS: Preictal discharge amplitude progressively increased, while PID interval gradually decreased toward seizure onset. The autocorrelation coefficients of PID channels were significantly higher during PID stage than before PID stage. There was an overlap between channels with PIDs and seizure onset channels (80.77%). CONCLUSIONS: Preictal discharges emerge prior to ictal event, with a dynamic change and a spatial correlation with seizure onset zone. These findings deepen our understanding of seizure generation and help early prediction and localization of seizure onset zone. PMID- 29794618 TI - A Flawed Design Produces Flawed Results. PMID- 29794619 TI - Reply to Dr Peltz. PMID- 29794620 TI - Cleveland Clinic Postural Stability Index Norms for the Balance Error Scoring System. AB - INTRODUCTION: Despite the widespread utilization of the Balance Error Scoring System (BESS) in the evaluation of concussion, it has been criticized for its error-based scoring that is susceptible to floor and ceiling effects and substantial inter-rater variability. A biomechanical outcome, Cleveland Clinic Postural Stability Index (CC-PSI), has been developed as an alternative to subjective BESS scoring. The CC-PSI uses inertial sensor data within a mobile device to provide an objective measure of postural sway during the BESS. This project aimed to determine the effect of age and sex on the CC-PSI and report normative values for healthy, active children, adolescents, and young adults. METHODS: A cross-sectional sample of 6762 student-athletes completed BESS testing. Participants were stratified according to three age groups for each sex. The groups included the following: youth (age, 5-13 yr), males (n = 360), females (n = 246); high school (age, 14-18 yr), males (n = 3743), females (n = 1673); and college (age, 19-23 yr), males (n = 497), females (n = 243). Percentile rankings were determined for each participant to characterize movement of COM in the medial-lateral, anterior-posterior, and trunk rotation directions relative to the entire cohort during the BESS stances. RESULTS: Overall, postural stability was worse in youth compared with high school and collegiate athletes. Specifically, the CC-PSI was significantly worse in youth male athletes compared with high school and collegiate male athletes (P < 0.001). Females exhibited significantly better scores compared with males in youth and high school cohorts (P < 0.01). CONCLUSIONS: The CC-PSI provides a quantitative, objective measure of postural stability, overcoming the limitations associated with conventional BESS scoring. Optimal concussion management should use objective age- and sex-specific values in the evaluation of postural stability. The normative values of the CC-PSI may be used in the absence of a baseline BESS evaluation to aid clinical decision making. PMID- 29794622 TI - Deactivating ICDs at end of life. PMID- 29794623 TI - Peruvian immersion course teaches cultural competence. PMID- 29794625 TI - Damage control: Differentiating incontinence-associated dermatitis from pressure injury. PMID- 29794626 TI - Caring for a patient with a desmoid tumor. PMID- 29794627 TI - It never goes away. PMID- 29794628 TI - Workplace incivility: How do you address it? PMID- 29794629 TI - Making the case for harm reduction programs for injection drug users. PMID- 29794630 TI - Providing evidence-based practices for patients with hip fractures. PMID- 29794631 TI - Homeless people: Nursing care with dignity. PMID- 29794632 TI - A questionable case of meningitis. PMID- 29794633 TI - Best practices for unclogging feeding tubes in adults. PMID- 29794634 TI - Retail clinics: Preparing patients to travel abroad. PMID- 29794635 TI - National Library of Medicine resources for patients. PMID- 29794637 TI - Treatment of Facial Hypopigmented Scars by the Laser Hole Technique Using a Nonfractional Carbon Dioxide Laser in Asians. AB - BACKGROUND: Facial hypopigmented scars are usually characterized by white color and a glossy surface. To correct the two problems simultaneously, the authors attempted to induce persistent postinflammatory hyperpigmentation for color and to build multiple pitted scars like facial skin pores for texture. This study describes a laser hole method using a traditional nonfractional carbon dioxide laser for treatment of facial hypopigmented scars and evaluates the clinical results. METHODS: Forty-three facial hypopigmented scars in 27 patients were treated, excluding protruding or thick scars. A carbon dioxide laser was set in the superpulse mode by continuous delivery. Multiple small holes were made in the scar at a distance of 1 to 3 mm. Each laser hole was produced by continuously repeated shots at one point until the deep dermis was involved. All lesions were exposed without protection. At 1 or 2 months after initial treatment, the remaining hypopigmentation was treated by the same procedure. RESULTS: Treatment sessions were performed once for nine scars, twice for 22 scars, and three times for 12 scars. In most cases, postinflammatory hyperpigmentation was slightly diminished but maintained until the last follow-up. The fine irregular surface with multiple pitted scars was similar to that of normal skin. Scar improvement evaluation showed marked or excellent in 39 scars (90.7 percent) and minimal or partial in four deep or thick scars. CONCLUSION: The laser hole technique using a nonfractional carbon dioxide laser may be an excellent option for simultaneously treating the color and texture of superficial or thin hypopigmented facial scars in Asians. PMID- 29794638 TI - The Implications of Barbed Sutures on Scar Aesthetics: A Systematic Review. AB - BACKGROUND: Barbed sutures have become increasingly popular in the field of aesthetic plastic surgery, particularly in body contouring and breast operations, in which the use of barbed sutures may offer both time and cost savings. Scar aesthetics is an important outcome for both surgeons and patients in these procedures; however, there is a paucity of studies assessing the aesthetic outcome of barbed sutures with regard to scarring. METHODS: A systematic review of the PubMed, EMBASE, and Cochrane databases was performed from the date of their inception through July of 2017 using the search terms "barbed suture" combined with "scar" or "wound." Studies were included if they were prospective, evaluator-blind, randomized, controlled trials; closed the dermal layer of incisions using barbed sutures; and included an evaluator-blind aesthetic assessment of scarring. RESULTS: Six prospective, randomized, controlled trials met inclusion criteria. The cosmetic result of scars in 926 patients was evaluated after an average of 8.1 months. Five of the six controlled trials found the aesthetic results of wounds closed with barbed sutures to be equivalent to those closed with traditional sutures, and one study showed significantly superior aesthetic results with barbed sutures. Use of barbed sutures resulted in shorter operating times in four of the five studies that timed incision closure. Similar complication rates were observed in all evaluated studies. CONCLUSION: Based on this systematic review, the majority of studies concluded that there were no differences in scarring aesthetics when dermal layers were closed using barbed sutures compared with traditional suturing techniques. PMID- 29794639 TI - Comparing Therapeutic versus Prophylactic Nipple-Sparing Mastectomy: Does Indication Inform Oncologic and Reconstructive Outcomes? AB - BACKGROUND: Initially performed only in prophylactic cases, indications for nipple-sparing mastectomy have expanded. Trends and surgical outcomes stratified by nipple-sparing mastectomy indication have not yet been fully examined. METHODS: Demographics and outcomes for all nipple-sparing mastectomies performed from 2006 to 2017 were compared by mastectomy indication. RESULTS: A total of 1212 nipple-sparing mastectomies were performed: 496 (40.9 percent) for therapeutic and 716 (59.1 percent) for prophylactic indications. Follow-up time was similar between both the therapeutic and prophylactic nipple-sparing mastectomy groups (47.35 versus 46.83 months, respectively; p = 0.7942). Therapeutic nipple-sparing mastectomies experienced significantly greater rates of major (p = 0.0165) and minor (p = 0.0421) infection, implant loss (p = 0.0098), reconstructive failure (p = 0.0058), and seroma (p = 0.0043). Rates of major (p = 0.4461) and minor (p = 0.2673) mastectomy flap necrosis and complete (p = 0.3445) and partial (p = 0.7120) nipple necrosis were equivalent. The overall rate of locoregional recurrence/occurrence per nipple-sparing mastectomy was 0.9 percent: 2.0 percent in therapeutic nipple-sparing mastectomies and 0.1 percent in prophylactic nipple-sparing mastectomies (p < 0.0001). CONCLUSIONS: Approximately 40 percent of nipple-sparing mastectomies are currently performed for therapeutic indications. Therapeutic nipple-sparing mastectomies had higher rates of infectious complications and reconstructive failure. Rates of locoregional cancer recurrence/occurrence are low, but occur significantly more often after therapeutic nipple-sparing mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 29794640 TI - Prospective Evaluation of Obese Patients Undergoing Autologous Abdominal Free Flap Breast Reconstruction. AB - BACKGROUND: Obesity has been viewed as a relative contraindication against autologous free flap breast reconstruction because of increased risks of complications, including flap loss. METHODS: The authors conducted a prospective analysis of obese patients undergoing autologous breast reconstruction. RESULTS: Overall, 72 patients (average age, 48.5 years; average body mass index, 35.7 kg/m) underwent abdominal free flap breast reconstruction. There were 43 bilateral reconstructions and the remainder were unilateral (n = 115 flaps). There were 67 muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) flaps (58.3 percent), 44 deep inferior epigastric perforator (DIEP) flaps (38.2 percent), two free bipedicle DIEP flaps, one superficial inferior epigastric perforator flap, and one free TRAM flap. Forty-two patients (58.3 percent) had prior radiation, and 51 (70.8 percent) had prior chemotherapy. Forty-three patients (59.7 percent) underwent delayed reconstruction and 21 (29.2 percent) underwent immediate reconstruction. Eight patients (11.1 percent) had bilateral reconstruction, with one breast reconstructed in an immediate and the other in a delayed fashion. Half of the patients (n = 36) had mesh placed in an underlay fashion to reinforce the donor site. Regarding breast complications, there were 11 wound dehiscences, one hematoma, one infection, and two patients with mastectomy skin flap necrosis. Twelve patients had donor-site wound healing complications, there were four infections, and three patients developed a bulge/hernia. There were no flap losses. Comparison to historic controls demonstrated no significant differences in overall flap loss rates (p = 0.061) or donor-site bulge/hernia (p = 0.86). CONCLUSION: Autologous abdominal free flaps can be performed safely in obese patients without increased risks for donor-site bulge/hernia or flap loss compared to nonobese patients; however, patients should be counseled carefully regarding the potential risks of complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 29794641 TI - Vertical Spacing of Perforators in Deep Inferior Epigastric Perforator Flap Breast Reconstruction Can Affect the Outcomes. AB - BACKGROUND: The present study aimed to evaluate the influence of vertical location and spacing of perforators within flaps on the outcomes of deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: Patients who underwent unilateral breast reconstruction with unipedicle DIEP flaps were identified. They were categorized into cohorts based on the entry of perforators in the middle third (cohort 1), upper third (cohort 2), and multiple third parts (cohort 3) of the flaps. Perfusion-related complications including fat necrosis diagnosed with ultrasound and donor-site morbidity were compared between the cohorts. RESULTS: A total of 287 patients were analyzed, including 51 in cohort 1, 75 in cohort 2, and 161 in cohort 3. The cohorts were well matched, except for a greater number of perforators and more frequent harvest of both medial and lateral row perforators in cohort 3. Rates of overall perfusion-related complications and fat necrosis differed significantly between cohorts, with the highest rates in cohort 2. Fat necrosis occurred predominantly in the caudal portion of the flap in cohort 2, whereas it was relatively evenly distributed in the cephalic and caudal portions in cohorts 1 and 3. Rates of donor-site complications were similar across the cohorts. Multivariate analyses demonstrated that vertical spacing of perforators had an independent influence on developing perfusion-related complications and fat necrosis, showing that cohort 2 had significantly higher odds compared with cohorts 1 and 3, respectively. CONCLUSION: Vertical spacing of perforators might affect the risk of perfusion related complications in DIEP flap breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 29794642 TI - Modified Nipple Flap with Free Areolar Graft for Component Nipple-Areola Complex Construction: Outcomes with a Novel Technique for Chest Wall Reconstruction in Transgender Men. AB - BACKGROUND: A primary goal in chest wall reconstruction ("top surgery") for trans men is achieving a symmetric, aesthetically pleasing position of the reconstructed male nipple-areola complex. METHODS: The senior author's (A.H.) technique for component nipple-areola complex creation in chest wall reconstruction for trans men with a modified skate flap and free areolar graft, in conjunction with double-incision mastectomy, is described. A retrospective analysis of 50 consecutive patients who underwent primary, bilateral chest wall reconstruction with this technique was undertaken for the period of March of 2015 to October of 2016. RESULTS: The average patient age was 30.64 years, and the average body mass index was 28.54 kg/m. Eighty-two percent of the sample received preoperative testosterone therapy, and average operative time was 2 hours 59 minutes. Average overall mastectomy specimen weight was 627.80 g, average length of hospital stay was 0.96 days, and average follow-up duration was 19.02 months. Complications occurred in five patients (10 percent), including seroma (4 percent), cellulitis (2 percent), hematoma (2 percent), and suture granuloma (2 percent). Only five patients (10 percent) underwent postoperative revision to adjust nipple-areola complex size, projection, or symmetry. Twenty-eight patients (56 percent) underwent secondary revisions, including scar revisions (56 percent), liposuction (12 percent), and fat grafting (2 percent). CONCLUSION: The use of a modified nipple flap and free areola graft in transgender chest wall reconstruction for trans men allows for flexible, component construction of the male nipple-areola complex in a safe and effective manner. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 29794643 TI - Pediatric Gastrointestinal Posttransplant Lymphoproliferative Disorder: Incidence, Clinical Characteristics, and Impact of Major Surgical Interventions Upon Overall Survival. AB - Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation. A common site for PTLD development is the gastrointestinal (GI) tract. The purpose of this study was to evaluate the incidence, clinical features, and overall survival of pediatric patients with GI PTLD, and to assess whether major surgical interventions increased mortality. Records of pediatric transplant patients who developed GI-PTLD between January 2000 and June 2015 were retrospectively reviewed at our institution. Of 814 patients who received solid organ transplants, 34 (4%) developed GI-PTLD. Lung and multiorgan transplants had the highest incidence of GI-PTLD (both 11%). Patients often had multisite GI involvement (47%). Within the first year of transplantation, 38% of the 34 patients developed GI-PTLD. Of the patients with Epstein-Barr Virus-positive disease, 12/22 (55%) presented in the first 12 months of transplantation, compared with only 1/12 (8%) of the patients with Epstein Barr Virus-negative disease (P=0.002). Major surgical interventions were required in 41% of patients; overall survival rate for these surgical patients was 71%, compared with 60% for patients not requiring major surgical interventions (P=0.49). Despite multimodal treatments, overall survival remains poor for patients with GI-PTLD; however, major surgical intervention did not significantly impact overall survival in this cohort. PMID- 29794644 TI - Increased Survival for Children With Acute Myeloid Leukemia Results From Improved Postrelapse Treatment. AB - BACKGROUND: The treatment for pediatric acute myeloid leukemia (AML) has not changed significantly over the past 3 decades, yet outcomes have improved with cure rates increasing from 30% to over 60% of all newly diagnosed children over this period. This improvement in survival has been attributed to both treatment intensification and improved supportive care over the decades, although the precise impact of each remains unknown. PATIENTS AND METHODS: We retrospectively analyzed a unique cohort of 276 patients with de novo AML diagnosed in childhood, all treated with the same chemotherapy protocol over a 25-year period from 1986 to 2012. RESULTS: The contemporary cohort (2000-2012), compared with the historical cohort (1986-1999) had significantly improved overall survival (75% vs. 50%; hazard ratio, 2.17; 95% confidence interval, 1.15-2.93), lower disease related mortality (38% vs. 19%, P=0.02) and were significantly more likely to receive an allogeneic transplant after relapse (stem cell transplantation [SCT], 73% vs. 12%; P<0.0001). Allogeneic transplant postrelapse was associated with a significantly improved survival across the entire cohort (overall survival 50% for allogeneic SCT vs. 12% for autologous or none, P<0.0001). There was no significant difference between the contemporary and historical cohorts in treatment-related mortality (13% vs. 7%, P=0.42) or relapse rates after induction (50% in older cohort vs. 40% in recent era, P=0.25), suggesting consistency of induction treatment efficacy and toxicity across the 2 periods. CONCLUSIONS: This data suggests improved survival in pediatric AML in the modern era has predominantly resulted from changes in treatment after relapse, including increased use of allogeneic SCT. PMID- 29794645 TI - Evaluation of the Use of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients. AB - A neurokinin-1 (NK1) receptor antagonist is recommended with a 5-HT3 receptor antagonist and dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving highly emetogenic chemotherapy. Data for fosaprepitant use in pediatric patients is lacking. A retrospective chart review was conducted using an electronic medical record to characterize the use of fosaprepitant in patients aged 10 months to 18 years at a single institution from August 2015 to January 2017. Thirty-nine patients received fosaprepitant 4 mg/kg (maximum, 150 mg) for prevention of CINV, and 35 were included in the analysis. Ten patients 5 years of age or older who received fosaprepitant after October 2016 were eligible for a follow-up phone call to assess control of delayed CINV. Complete control of emesis was observed in 89% of patients during the acute phase, 63% during the delayed phase, and 60% overall. Overall incidence of nausea as documented in the medical record was 43%. Among the 10 patients who completed follow-up phone calls, 30% experienced emesis and 50% experienced nausea after discharge. Fosaprepitant may be safe and effective in the prevention of CINV in pediatric patients as young as 10 months of age. PMID- 29794646 TI - Plasma Hepcidin Levels in Healthy Children: Review of Current Literature Highlights Limited Studies. AB - BACKGROUND: There are few studies that highlight pediatric hepcidin reference ranges especially from Asian subcontinent. In current study, plasma from 131 children (72 boys and 59 girls; 1 to 12 y) was analyzed for hepcidin-25 by enzyme linked immunosorbent assay. OBSERVATIONS: The median (interquartile range) plasma hepcidin in boys was 21.89 ng/mL (16.50 to 51.70 ng/mL) and girls was 21.95 ng/mL (19.20 to 47.70 ng/mL). No statistically significant difference (P=0.937) of plasma hepcidin levels in sex was noted. However, multiple regression analysis revealed a significant correlation between plasma hepcidin levels and ferritin (P=0.000). CONCLUSIONS: Our study results highlight relatively lower median hepcidin values in children aged 1 to 12 years as compared with western data. This may be attributed to either lack of a harmonized and standard enzyme-linked immunosorbent assay detection methodology or to presence of clinically significant polymorphisms in hepcidin gene in our population. PMID- 29794647 TI - Management of Herpes Simplex Virus Keratitis in the Pediatric Population. AB - Herpes simplex virus (HSV) keratitis is a highly prevalent and visually disabling disease in both the pediatric and adult population. While many studies have investigated the treatment of HSV keratitis in adult patients, few have focused on managing this condition in children. Children are at particularly high risk for visual morbidity due to unique challenges in diagnosis and treatment, and the often more aggressive disease course that results in corneal scarring, and subsequently amblyopia. This review presents the pathogenesis and most current recommendations for the medical and surgical management of HSV keratitis in the pediatric population. PMID- 29794649 TI - Decrease in the Prevalence of Methicillin-Resistant Staphylococcus aureus Nasal Colonization of Children Admitted to Driscoll Children's Hospital. AB - Compared with a similar 2005 study, this 2016 study showed a significant decrease from 22% to 3% in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization in children admitted to our facility. Of the sampled 360 children, 21% were colonized with Staphylococcus aureus and 14% of those isolates were MRSA, whereas 61% of the isolates in 2005 were MRSA. PMID- 29794648 TI - Inappropriate Antibiotic Prescribing for Acute Bronchitis in Children and Impact on Subsequent Episodes of Care and Treatment. AB - BACKGROUND: To examine whether inappropriate antibiotic treatment for an initial bout of acute bronchitis in childhood affects patterns of future healthcare utilization and antibiotic prescribing. METHODS: We conducted a retrospective analysis of children with at least one acute bronchitis episode, defined as the 14-day period following an acute bronchitis visit, born in 2008 and followed through 2015 in a nationally representative commercial claims database. We predicted the likelihood of returning for a subsequent acute bronchitis episode, and being prescribed an antibiotic as part of that episode, as a function of whether or not the child was prescribed an antibiotic as part of the first acute bronchitis episode controlling for patient, provider, and practice characteristics. RESULTS: Children prescribed an antibiotic as part of their initial acute bronchitis episode were more likely both to have a subsequent acute bronchitis episode (HR=1.23, 95% CI 1.17-1.30) and to be prescribed an antibiotic as part of that second episode (HR=2.13, 95% CI 1.99-2.28) compared to children who were not prescribed as part of their first episode. Children diagnosed with asthma were more likely to experience a second visit for acute bronchitis, but less likely to receive an antibiotic as part of that second episode. CONCLUSIONS: Inappropriate antibiotic prescribing for a child's initial acute bronchitis episode of care predicted likelihood of subsequent acute bronchitis episodes and antibiotic prescriptions. Providers should consider the downstream effect of inappropriate antibiotic prescribing for acute bronchitis in childhood. PMID- 29794650 TI - Spinal Tuberculosis in Young Human Immunodeficiency Virus-Exposed Infants: Two Cases of Probable Congenital Transmission. AB - The presentation of congenital tuberculosis (TB) is varied, with frequent extrapulmonary disease, but congenital spinal TB has been rarely reported. We present two cases of spinal TB (one confirmed, one clinical diagnosis) in HIV exposed infants with likely congenital transmission. Increased vigilance for congenital TB, including uncommon presentations, is needed, particularly in countries with high HIV and TB prevalence. PMID- 29794651 TI - Optimizing Gentamicin Dosing in Pediatrics Using Monte Carlo Simulations. AB - Gentamicin is known to have concentration-dependent bactericidal activity and its nephrotoxic effect is well described. We developed a population pharmacokinetic/pharmacodynamic model to optimize gentamicin dosing in pediatrics. Data were retrospectively collected for pediatric patients aged 1 month-12 years, admitted to general pediatric wards or ICUs and received gentamicin for suspected or proven gram-negative infections. at King Saud University Medical City, Riyadh, Saudi Arabia. A total of 306 gentamicin peak and trough concentrations sets from 107 patients were analyzed with mean (+/- SD) patient age and weight of 4.5 +/- 3.5 years and 16.7 +/- 10.8 kg, respectively. Gentamicin pharmacokinetics were adequately described with a one compartment system (R = 0.82, bias = 1.75% and precision = 88% for population predictions and R = 0.94, bias = 5 % and precision = 29 % for individual predictions). The gentamicin pharmacokinetic parameters were as follows: volume of distribution = 8.9 L, total body clearance = 2.8 L/hr for a 20 kg patient. Monte Carlo simulations showed that doses of 5-6 mg/kg/dose once daily are adequate only to treat infections with gram negative organisms having MIC less than 1 mcg/ml. While, at MIC of 1 mcg/ml, higher doses (7-8 mg/kg/dose once daily) are needed to maximize the efficacy of gentamicin. However, at MIC of 2 mcg/ml, even a 10 mg/kg dose showed poor target attainment (52 %). The finding of this study highlights the need to reevaluate the current breakpoints of gentamicin, and also to assess the safety of higher doses of gentamicin in pediatrics. PMID- 29794652 TI - Pneumocystis Infection in Children: National Trends and Characteristics in the United States, 1997-2012. AB - BACKGROUND: Although the epidemiology of immunocompromising condition in children has evolved over time, updated epidemiology of pediatric pneumocystis infection in the US is not available. METHODS: We performed a retrospective analysis using the Kids' Inpatient Database, a nationally representative sample of US pediatric hospital discharges collected in 1997, 2000, 2003, 2006, 2009, and 2012. pneumocystis cases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification code 136.3 among children aged 0 18 years. Demographic data of cases with and without mortality were compared. RESULTS: We identified 1,902 (standard error, SE: 95) pneumocystis cases during the study period. The pneumocystis hospitalization rate decreased from 7.5 (SE: 0.91) to 2.7 (SE: 0.31) per a million US children from 1997 to 2012 (63.2% decrease). Cases with human immunodeficiency virus (HIV) infection decreased from 285 (SE: 56) cases in 1997 to 29 (SE: 7) cases in 2012, whereas hematologic malignancy and primary immunodeficiency became more prominent. Infants were the most commonly affected (510 cases [SE: 40]). All-cause in-hospital mortality was 11.7% (SE: 1.3%) and was particularly high among cases with hematopoietic stem cell transplant (HSCT) (32.4% [SE: 7.1%]) (p <0.001). CONCLUSIONS: Pneumocystis infection in children showed a marked decrease from 1997 to 2012 in the US, largely driven by the reduction in HIV-associated cases, and cases with non-HIV illnesses became more prominent. HSCT-associated cases had particularly high mortality. Clinicians should be aware of high risk groups that may benefit from chemoprophylaxis, particularly in infancy. PMID- 29794654 TI - Characterizing the Functional Decline of Older Women With Incident Urinary Incontinence. PMID- 29794653 TI - Viral Suppression in a Nationwide Sample of HIV-infected Children on Antiretroviral Therapy in Rwanda. AB - Rwanda has made significant progress in expanding pediatric antiretroviral treatment(ART) coverage. This was a nationwide, cross-sectional study of pediatric HIV suppression rates. Of 292 children on ART >=12 months, 68.8% achieved viral suppression <40 copies/ml, respectively. Rwanda achieved good pediatric viral suppression rates, comparable to those from other resource limited settings(RLS), yet more efforts are needed to achieve the UNAIDS 90-90-90 target. PMID- 29794655 TI - In Reply. PMID- 29794656 TI - Term Elective Induction of Labor and Pregnancy Outcomes Among Obese Women and Their Offspring. PMID- 29794657 TI - In Reply. PMID- 29794658 TI - ACOG Committee Opinion No. 729: Importance of Social Determinants of Health and Cultural Awareness in the Delivery of Reproductive Health Care. PMID- 29794659 TI - In Reply. PMID- 29794660 TI - ACOG Practice Bulletin No. 188: Prelabor Rupture of Membranes. PMID- 29794661 TI - In Reply. PMID- 29794662 TI - Outcomes of Planned Compared With Urgent Deliveries Using a Multidisciplinary Team Approach for Morbidly Adherent Placenta. PMID- 29794663 TI - In Reply. PMID- 29794664 TI - Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome. PMID- 29794665 TI - In Reply. PMID- 29794666 TI - Characterizing the Functional Decline of Older Women With Incident Urinary Incontinence: Correction. PMID- 29794669 TI - ACOG Publications. PMID- 29794670 TI - ACOG Practice Bulletin No. 194 Summary: Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Its etiology remains unknown, and treatment is largely symptom based and empirical. PCOS has the potential to cause substantial metabolic sequelae, including an increased risk of diabetes and cardiovascular disease, and these factors should be considered when determining long-term treatment. The purpose of this document is to examine the best available evidence for the diagnosis and clinical management of PCOS. PMID- 29794671 TI - ACOG Practice Bulletin No. 195 Summary: Prevention of Infection After Gynecologic Procedures. AB - Surgical site infection remains the most common complication of gynecologic procedures. Reducing surgical site infections has become a priority in the United States as part of a strong national commitment to measuring processes and improving outcomes of care for surgery. Implementing programs to reduce surgical site infections requires a collaborative approach that involves clinicians, nurses, and staff. The purpose of this document is to review the recommended interventions, including antibiotic prophylaxis, used to prevent infection after gynecologic procedures. PMID- 29794672 TI - ACOG Committee Opinion No. 737 Summary: Expedited Partner Therapy. AB - Sexually transmitted infections (STIs) disproportionately affect women and create a preventable threat to their fertility. One factor that contributes to young women's high rates of STIs is reinfection from an untreated sexual partner. One way to address this problem is through expedited partner therapy, the practice of treating the sexual partners of patients in whom STIs are diagnosed. Expedited partner therapy enables the obstetrician-gynecologist or other provider to give prescriptions or medications to patients to take to their partners without first examining these partners. Despite the effectiveness of expedited partner therapy, numerous legal, medical, practical, and administrative barriers hinder its routine use by obstetrician-gynecologists. The American College of Obstetricians and Gynecologists supports the use of expedited partner therapy as a method of preventing gonorrhea and chlamydial reinfection when a patient's partners are unable or unwilling to seek medical care. Expedited partner therapy should be accompanied by patient counseling and written treatment instructions for the patient's partner(s). Partners receiving expedited partner therapy should be encouraged to seek additional medical evaluation as soon as possible to discuss screening for other STIs, including human immunodeficiency virus (HIV) infection. PMID- 29794673 TI - ACOG Committee Opinion No. 738 Summary: Aromatase Inhibitors in Gynecologic Practice. AB - Aromatase inhibitors have been used for the treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions. For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of the risk of osteoporosis due to estrogen deficiency. Based on long-term adverse effects and complication safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding. For women with polycystic ovary syndrome and a body mass index greater than 30, letrozole should be considered first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate. Lifestyle changes that result in weight loss should be strongly encouraged. Aromatase inhibitors are a promising therapeutic option that may be helpful for the management of endometriosis-associated pain in combination therapy with progestins. PMID- 29794674 TI - ACOG Committee Opinion No. 739 Summary: The Late-Career Obstetrician Gynecologist. AB - The American Medical Association reported in 2015 that physicians 65 years and older currently represent 23% of the physicians in the United States. Unlike other professions such as commercial airline pilots, who by law must have regular health screenings starting at 40 years and must retire at 65 years, few health care institutions or systems have any policies regarding the late-career physician. Although there is an increase in accumulated wisdom and verbal knowledge with age, there is also an overall decline in recall memory, cognitive processing efficiency, and executive reasoning. The goal of physicians and health care institutions is to provide safe and competent care to their patients. Therefore, when considering the performance of a physician, the quality of care provided and safety of the patient are of the utmost importance. It is important to establish systems-based competency assessments to monitor and address physicians' health and the effect age has on performance and outcomes. Retention strategies can support areas of cognitive or technical decline while capitalizing on the aging doctor's strengths, and workplace adaptations should be adopted to help obstetrician-gynecologists transition and age well in their practice and throughout their careers. PMID- 29794675 TI - ACOG Committee Opinion No. 740 Summary: Gynecologic Care for Adolescents and Young Women With Eating Disorders. AB - The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines eating disorders as a "persistent disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food and that significantly impairs physical health or psychosocial functioning." The correct diagnosis of and distinction between eating disorders are important because the course, prognosis, and treatment may be vastly different. Although the age at peak incidence can vary depending on the eating disorder, these disorders commonly arise during adolescence. Adult and adolescent females with eating disorders may present with gynecologic concerns or symptoms, including irregular menses, amenorrhea, pelvic pain, atrophic vaginitis, and breast atrophy. Although formal diagnosis and treatment of eating disorders in adolescents are complex and outside the scope of practice for most general obstetrician-gynecologists, it is important that health care providers be comfortable with recognizing and screening at-risk patients. Recognizing risk factors for eating disorders can help to identify patients who should be further evaluated. Simply asking the patient how she feels about her weight, what she is eating, how much she is eating, and how much she is exercising can help identify at-risk patients. A physical examination and laboratory tests are valuable in the diagnosis of an eating disorder. Because eating disorders are complex and affect psychologic and physical health, a multidisciplinary approach is imperative. Although obstetrician-gynecologists are not expected to treat eating disorders, they should be familiar with the criteria that warrant immediate hospitalization for medical stabilization. PMID- 29794676 TI - ACOG Committee Opinion No. 741 Summary: Maternal Immunization. AB - Immunization is an essential part of care for adults, including pregnant women. Influenza vaccination for pregnant women is especially important because pregnant women who contract influenza are at greater risk of maternal morbidity and mortality in addition to fetal morbidity, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. Other vaccines provide maternal protection from severe morbidity related to specific pathogens such as pneumococcus, meningococcus, and hepatitis for at-risk pregnant women. Obstetrician-gynecologists and other obstetric care providers should routinely assess their pregnant patients' vaccination status. Based on this assessment they should recommend and, when possible, administer needed vaccines to their pregnant patients. There is no evidence of adverse fetal effects from vaccinating pregnant women with inactivated virus, bacterial vaccines, or toxoids, and a growing body of data demonstrate the safety of such use. Women who are or will be pregnant during influenza season should receive an annual influenza vaccine. All pregnant women should receive a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, as early in the 27-36-weeks-of gestation window as possible. PMID- 29794677 TI - ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Its etiology remains unknown, and treatment is largely symptom based and empirical. PCOS has the potential to cause substantial metabolic sequelae, including an increased risk of diabetes and cardiovascular disease, and these factors should be considered when determining long-term treatment. The purpose of this document is to examine the best available evidence for the diagnosis and clinical management of PCOS. PMID- 29794678 TI - ACOG Practice Bulletin No. 195: Prevention of Infection After Gynecologic Procedures. AB - Surgical site infection remains the most common complication of gynecologic procedures. Reducing surgical site infections has become a priority in the United States as part of a strong national commitment to measuring processes and improving outcomes of care for surgery. Implementing programs to reduce surgical site infections requires a collaborative approach that involves clinicians, nurses, and staff. The purpose of this document is to review the recommended interventions, including antibiotic prophylaxis, used to prevent infection after gynecologic procedures. PMID- 29794679 TI - ACOG Committee Opinion No. 737: Expedited Partner Therapy. AB - Sexually transmitted infections (STIs) disproportionately affect women and create a preventable threat to their fertility. One factor that contributes to young women's high rates of STIs is reinfection from an untreated sexual partner. One way to address this problem is through expedited partner therapy, the practice of treating the sexual partners of patients in whom STIs are diagnosed. Expedited partner therapy enables the obstetrician-gynecologist or other provider to give prescriptions or medications to patients to take to their partners without first examining these partners. Despite the effectiveness of expedited partner therapy, numerous legal, medical, practical, and administrative barriers hinder its routine use by obstetrician-gynecologists. The American College of Obstetricians and Gynecologists supports the use of expedited partner therapy as a method of preventing gonorrhea and chlamydial reinfection when a patient's partners are unable or unwilling to seek medical care. Expedited partner therapy should be accompanied by patient counseling and written treatment instructions for the patient's partner(s). Partners receiving expedited partner therapy should be encouraged to seek additional medical evaluation as soon as possible to discuss screening for other STIs, including human immunodeficiency virus (HIV) infection. PMID- 29794680 TI - ACOG Committee Opinion No. 738: Aromatase Inhibitors in Gynecologic Practice. AB - Aromatase inhibitors have been used for the treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions. For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of the risk of osteoporosis due to estrogen deficiency. Based on long-term adverse effects and complication safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding. For women with polycystic ovary syndrome and a body mass index greater than 30, letrozole should be considered first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate. Lifestyle changes that result in weight loss should be strongly encouraged. Aromatase inhibitors are a promising therapeutic option that may be helpful for the management of endometriosis-associated pain in combination therapy with progestins. PMID- 29794681 TI - ACOG Committee Opinion No. 739: The Late-Career Obstetrician-Gynecologist. AB - The American Medical Association reported in 2015 that physicians 65 years and older currently represent 23% of the physicians in the United States. Unlike other professions such as commercial airline pilots, who by law must have regular health screenings starting at 40 years and must retire at 65 years, few health care institutions or systems have any policies regarding the late-career physician. Although there is an increase in accumulated wisdom and verbal knowledge with age, there is also an overall decline in recall memory, cognitive processing efficiency, and executive reasoning. The goal of physicians and health care institutions is to provide safe and competent care to their patients. Therefore, when considering the performance of a physician, the quality of care provided and safety of the patient are of the utmost importance. It is important to establish systems-based competency assessments to monitor and address physicians' health and the effect age has on performance and outcomes. Retention strategies can support areas of cognitive or technical decline while capitalizing on the aging doctor's strengths, and workplace adaptations should be adopted to help obstetrician-gynecologists transition and age well in their practice and throughout their careers. PMID- 29794682 TI - ACOG Committee Opinion No. 740: Gynecologic Care for Adolescents and Young Women With Eating Disorders. AB - The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines eating disorders as a "persistent disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food and that significantly impairs physical health or psychosocial functioning." The correct diagnosis of and distinction between eating disorders are important because the course, prognosis, and treatment may be vastly different. Although the age at peak incidence can vary depending on the eating disorder, these disorders commonly arise during adolescence. Adult and adolescent females with eating disorders may present with gynecologic concerns or symptoms, including irregular menses, amenorrhea, pelvic pain, atrophic vaginitis, and breast atrophy. Although formal diagnosis and treatment of eating disorders in adolescents are complex and outside the scope of practice for most general obstetrician-gynecologists, it is important that health care providers be comfortable with recognizing and screening at-risk patients. Recognizing risk factors for eating disorders can help to identify patients who should be further evaluated. Simply asking the patient how she feels about her weight, what she is eating, how much she is eating, and how much she is exercising can help identify at-risk patients. A physical examination and laboratory tests are valuable in the diagnosis of an eating disorder. Because eating disorders are complex and affect psychologic and physical health, a multidisciplinary approach is imperative. Although obstetrician-gynecologists are not expected to treat eating disorders, they should be familiar with the criteria that warrant immediate hospitalization for medical stabilization. PMID- 29794683 TI - ACOG Committee Opinion No. 741: Maternal Immunization. AB - Immunization is an essential part of care for adults, including pregnant women. Influenza vaccination for pregnant women is especially important because pregnant women who contract influenza are at greater risk of maternal morbidity and mortality in addition to fetal morbidity, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. Other vaccines provide maternal protection from severe morbidity related to specific pathogens such as pneumococcus, meningococcus, and hepatitis for at-risk pregnant women. Obstetrician-gynecologists and other obstetric care providers should routinely assess their pregnant patients' vaccination status. Based on this assessment they should recommend and, when possible, administer needed vaccines to their pregnant patients. There is no evidence of adverse fetal effects from vaccinating pregnant women with inactivated virus, bacterial vaccines, or toxoids, and a growing body of data demonstrate the safety of such use. Women who are or will be pregnant during influenza season should receive an annual influenza vaccine. All pregnant women should receive a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during each pregnancy, as early in the 27-36-weeks-of gestation window as possible. PMID- 29794684 TI - Middle Ear Pressures in Wind Instrument Musicians. AB - OBJECTIVES: This study aimed to assess if playing wind instruments leads to a measurable increase in middle ear pressure during note generation and to provide evidence to clinicians to advise musicians undergoing middle ear surgery. STUDY DESIGN: An observational cohort study of 40 volunteers in 7 different wind instrument categories underwent tympanometry at rest and during note production. SETTING: Community. PATIENTS: Recreational musicians aged over 18 years recruited from the student body attending Birmingham University, UK. INTERVENTION: None. MAIN OUTCOME MEASURES: Tympanometry is used as a noninvasive measure of middle ear pressure. The pressure at which peak compliance occurred was taken as an indirect measure of middle ear pressure. The data produced at rest and during note production was statistically analysed with paired t testing and significance set at a p value less than 0.01. RESULTS: Overall a statistically significant increase in middle ear pressure change of 0.63 mm Hg (p = 0.0001) during note production was identified. Musicians playing the oboe and trumpet demonstrate the largest increase in middle ear pressure of 1.46 mm Hg (p = 0.0053) and 0.78 mm Hg (p = 0.0005) respectively. CONCLUSION: The data provided by this study gives evidence for the first time that playing wind instruments does increase middle ear pressure. Although the clinical significance of this is yet to be determined the authors would advise that musicians who undergo otological procedures should refrain from playing their instruments until full recovery has been achieved as advised by their clinician following direct microscopic review. PMID- 29794685 TI - Function, Applicability, and Properties of a Novel Flexible Total Ossicular Replacement Prosthesis With a Silicone Coated Ball and Socket Joint. AB - HYPOTHESIS: A total ossicular replacement prosthesis (TORP) with a silicone coated ball and socket joint (BSJ) is able to compensate pressure changes and therefore provide better sound transmission compared with rigid prostheses. BACKGROUND: Dislocation and extrusion are known complications after TORP reconstruction, leading to revisions and recurrent hearing loss. Poor aeration of the middle ear, scar tension, and static pressure variations in conjunction with rigid prosthesis design causes high tension at the implant coupling points. METHODS: A novel TORP prototype with a silicone coated BSJ has been developed. Experimental measurements were performed on nine fresh cadaveric human temporal bones of which five were used for a comparison between rigid TORP and flexible TORP tympanoplasty. The middle ear transfer function was measured at ambient pressure and at 2.5 kPa, both positive and negative pressure, applied in the ear canal. RESULTS: The flexible TORP design yields a better transmission of sound after implantation and at negative pressure inside the tympanic cavity, compared with rigid TORP. In average, it provides an equivalent sound transfer like the intact middle ear. At positive pressure, the flexible TORP performs slightly worse. Both performed worse than the intact middle ear, which is related to an uplifting of the prostheses. CONCLUSION: The findings may be considered preliminary as this experimental study was limited to just one of the many different possible situations of tympanoplasty and it involved a small sample size. Nevertheless, the results with the flexible TORP were promising and could encourage further investigations on such prostheses. PMID- 29794686 TI - Predicting Performance and Non-Use in Prelingually Deaf and Late-Implanted Cochlear Implant Users. AB - OBJECTIVE: To analyze postoperative hearing performance and independent predictors of speech perception and to assess cochlear implant nonuse in adults with prelingual deafness who received an implant during adulthood. DESIGN: Retrospective cohort study including all prelingually deaf adults who received a cochlear implant at the University Medical Center Utrecht between 2000 and 2013. SETTING: Tertiary referral center. PATIENTS: Included were a total of 48 prelingually deaf patients diagnosed with severe to profound sensorineural hearing loss before the age of 2 years who received their implants during adulthood. MAIN OUTCOME MEASURES: Postoperative monosyllabic word and sentence recognition scores. RESULTS: The average maximum postoperative monosyllabic word score for all subjects was 25% correct. Preoperative speech perception and the extent of preoperative residual hearing were both positive independent predictors of postoperative speech recognition, explaining 47% of the variance. Almost half of the population experienced only little (27%) or no benefit (21%) of their implants in daily communication. These patients were more likely to have either no or only low-frequency residual hearing. Eventually, all subjects without any benefit became non-user. CONCLUSIONS: Postoperative performance of adult, prelingually deaf cochlear implant candidates, with long-term deafness is dependent on their preoperative speech perception and residual hearing. Candidates who have negligible residual hearing are expected to have no or only limited postoperative benefit of their implants and are at risk of becoming nonusers. PMID- 29794687 TI - The Human Cochlear Aqueduct and Accessory Canals: a Micro-CT Analysis Using a 3D Reconstruction Paradigm. AB - OBJECTIVE: We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery. METHODS: An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or "cropping" of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen. RESULTS: The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus. CONCLUSION: Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent "castings" of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three dimensionally. PMID- 29794689 TI - The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures. AB - BACKGROUND: The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. We hypothesized that FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures. METHODS: Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(-) patients was considered positive if therapeutic intervention was required. RESULTS: During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 +/- 2 years and Injury Severity Score was 50 +/- 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%. CONCLUSION: Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these multisystem trauma patients and requires further study. REBOA placement should be considered in hemodynamically unstable pelvic fracture patients who are FAST(-), while laparotomy should be used in FAST(+) patients. LEVEL OF EVIDENCE: Therapeutic, level IV. PMID- 29794688 TI - Giant Temporal Lobe Abscess in a Patient With Ectodermal Dysplasia. AB - OBJECTIVE: To present the first reported case of a temporal lobe abscess in a patient with ectodermal dysplasia (ED). To increase awareness among neurotologists of the otological manifestations and complications of ED, we describe a conservative approach in comparison with the surgical strategies to repair bony defects of the tegmen tympani. STUDY DESIGN: Clinical capsule report. PATIENT: A 44-year-old man with ED presented with retroauricular pain and high grade fever after Eustachian tube catheterizations to treat an effusive otitis media. Since many signs indicated meningitis, a computed tomography (CT) scan of the brain was performed, and an extensive intraparenchymal mass was detected. Magnetic Resonance Images (MRI) confirmed a brain abscess of the right temporal lobe. INTERVENTIONS: Surgical drainage of the abscess through craniotomy, antimicrobial therapy, and strict follow-up. MAIN OUTCOME MEASURES: Clinical symptoms and radiological signs. RESULTS: After craniotomy, the antimicrobial therapy was administered for 8 weeks. Postoperative high resolution TC of the petrous bone showed the presence of material with a soft tissue signal in the right middle ear and dehiscent anterior tegmen tympani. The location of the bony defect in association with the good clinical outcome with medical therapy mitigated against a first choice otosurgical approach to repair the dehiscence. Serial MRI scans provided proof of complete remission and no relapse occurred during a 2-year follow-up. CONCLUSIONS: Patients with ED can present with chronic otitis media and tegmen tympani defects, predisposing them to serious complications. Imaging is mandatory, and the optimum treatment requires assessment of various factors. PMID- 29794690 TI - Validation of the American Association for the Surgery of Trauma emergency general surgery grade for skin and soft tissue infection. AB - INTRODUCTION: Skin and soft tissue infections (SSTIs) present with variable severity. The American Association for the Surgery of Trauma (AAST) developed an emergency general surgery (EGS) grading system for several diseases. We aimed to determine whether the AAST EGS grade corresponds with key clinical outcomes. METHODS: Single-institution retrospective review of patients (>=18 years) admitted with SSTI during 2012 to 2016 was performed. Patients with surgical site infections or younger than 18 years were excluded. Laboratory Risk Indicator for Necrotizing Fasciitis score and AAST EGS grade were assigned. The primary outcome was association of AAST EGS grade with complication development, duration of stay, and interventions. Secondary predictors of severity included tissue cultures, cross-sectional imaging, and duration of inpatient antibiotic therapy. Summary and univariate analyses were performed. RESULTS: A total of 223 patients were included (mean +/- SD age of 55.1 +/- 17.0 years, 55% male). The majority of patients received cross sectional imaging (169, 76%) or an operative procedure (155, 70%). Skin and soft tissue infection tissue culture results included no growth (51, 24.5%), monomicrobial (83, 39.9%), and polymicrobial (74, 35.6%). Increased AAST EGS grade was associated with operative interventions, intensive care unit utilization, complication severity (Clavien-Dindo index), duration of hospital stay, inpatient antibiotic therapy, mortality, and hospital readmission. CONCLUSION: The AAST EGS grade for SSTI demonstrates the ability to correspond with several important outcomes. Prospective multi-institutional study is required to determine its broad generalizability in several populations. LEVEL OF EVIDENCE: Prognostic, level IV. PMID- 29794691 TI - Featured Articles for CME Credit June 2018. PMID- 29794693 TI - The Impact of Mastectomy Weight on Reconstructive Trends and Outcomes in Nipple Sparing Mastectomy: Progressively Greater Complications with Larger Breast Size. AB - BACKGROUND: Reconstructive trends and outcomes for nipple-sparing mastectomy continue to be defined. The graduated impact of breast size and mastectomy weight remains incompletely evaluated. METHODS: All patients undergoing nipple-sparing mastectomy from 2006 to June of 2016 were identified. Demographics and outcomes were analyzed and stratified by mastectomy weight of 800 g or higher (large group), between 799 and 400 g (intermediate group), and less than 400 g (small group). RESULTS: Of 809 nipple-sparing mastectomies, 66 (8.2 percent) had mastectomy weights of 800 g or higher, 328 (40.5 percent) had mastectomy weights between 799 and 400 g, and 415 nipple-sparing mastectomies (51.3 percent) had mastectomy weights less than 400 g. Nipple-sparing mastectomies in the large group were significantly more likely to be associated with major mastectomy flap necrosis (p = 0.0005), complete nipple-areola complex necrosis (p < 0.0001), explantation (p < 0.0001), cellulitis treated with oral (p = 0.0008) and intravenous (p = 0.0126) antibiotics, abscess (p = 0.0254), and seroma (p = 0.0126) compared with those in the intermediate group. Compared with small nipple sparing mastectomies, patients in the large group had greater major mastectomy flap necrosis (p < 0.0001), complete (p < 0.0001) and partial (p = 0.0409) nipple areola complex necrosis, explantation (p < 0.0001), cellulitis treated with oral (p < 0.0001) and intravenous (p < 0.0001) antibiotics, abscess (p = 0.0119), and seroma (p < 0.0001). Patients in the intermediate group were more likely to experience major (p < 0.0001) and minor (p < 0.0001) mastectomy flap necrosis, complete (p = 0.0015) and partial (p < 0.0001) nipple-areola complex necrosis, cellulitis treated with oral antibiotics (p = 0.0062), and seroma (p = 0.0248) compared with those undergoing small nipple-sparing mastectomies. Larger mastectomy weights were significant predictors of complications on logistic regression analysis. CONCLUSION: Reconstructive and ischemic complications in nipple-sparing mastectomy are progressively greater as mastectomy weight and breast size increase. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 29794694 TI - Does Hormone Therapy Use Increase Perioperative Complications in Abdominally Based Microsurgical Breast Reconstruction? AB - BACKGROUND: The use of hormone therapy (tamoxifen and aromatase inhibitors) has been shown to increase venous thromboembolism. As breast cancer patients undergoing microsurgical breast reconstruction are often receiving hormone therapy, it is unclear whether this increased thrombotic risk is associated with increased flap loss. METHODS: A retrospective review was performed on patients undergoing abdominally based microsurgical breast reconstruction at an academic institution from 2004 to 2015. Patients were divided by use of hormone therapy at the time of surgery. Complication rates, including complete or partial flap loss and overall complications, were compared and analyzed using univariate and logistic regression models. RESULTS: Among a total of 853 patients (1253 flaps), 193 patients (269 flaps) were receiving hormone therapy and 660 patients (984 flaps) were not. Patients on hormone therapy had higher rates of previous breast surgery, advanced cancer stage, chemoradiation before reconstruction, and delayed and unilateral reconstruction. There were no statistically significant differences between hormone therapy patients and nontherapy patients in complete flap loss (1.0 percent versus 1.1 percent) and partial flap loss (2.2 percent versus 1.5 percent). Hypertension and previous breast surgery were the only independent risk factors for minor complications (adjusted OR, 2.1; 95 percent CI, 1.3 to 3.6; p = 0.005; and adjusted OR, 1.8; 95 percent CI, 1.2 to 2.7; p = 0.009, respectively) and overall complications (adjusted OR, 2.2; 95 percent CI, 1.3 to 3.7; p = 0.004; and adjusted OR, 1.9; 95 percent CI, 1.3 to 3.0; p = 0.003, respectively). CONCLUSIONS: Hormone therapy was not associated with a higher incidence of complete or partial flap loss or overall complications. The authors propose an individualized approach to the preoperative cessation of tamoxifen or aromatase inhibitors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 29794695 TI - BRCA Mutations in the Young, High-Risk Female Population: Genetic Testing, Management of Prophylactic Therapies, and Implications for Plastic Surgeons. AB - Growing public awareness of hereditary breast cancers, notably BRCA1 and BRCA2, and increasing popularity of personalized medicine have led to a greater number of young adult patients presenting for risk-reduction mastectomies and breast reconstruction. Plastic surgeons must be familiar with treatment guidelines, necessary referral patterns, and particular needs of these patients to appropriately manage their care. Genetic testing for BRCA1 and BRCA2 is most often reserved for patients older than the age of consent, and can be performed in the young adult population (aged 18 to 25 years) with the appropriate preemptive genetic counseling. Subsequent risk-reduction procedures are usually delayed until at least the latter end of the young adult age range, and must be considered on an individualized basis with regard for a patient's level of maturity and autonomy. Prophylactic mastectomies in young adults also can serve to aid the unique psychosocial needs of this population, although the long-term psychological and physical ramifications must be considered carefully. With the development of nipple-sparing mastectomy and improvement in reconstructive techniques, risk-reducing surgery has become more accepted in the younger population. Immediate, implant-based reconstruction is a common reconstructive technique in these patients but requires extensive discussion regarding reconstructive goals, the risk of possible complications, and long-term implications of these procedures. Comprehensive, continuous support with multispecialty counseling is necessary throughout the spectrum of care for the high-risk, young adult patient. PMID- 29794696 TI - Motiva Ergonomix Round SilkSurface Silicone Breast Implants: Outcome Analysis of 100 Primary Breast Augmentations over 3 Years and Technical Considerations. AB - BACKGROUND: Macrotextured anatomical implants are frequently used in aesthetic breast surgery; however, several safety concerns linked to this implant type have been raised recently. In an attempt to address these shortcomings, Motiva Ergonomix implants have been introduced. Here, the authors describe the current world's largest experience with these novel devices in aesthetic breast surgery and evaluate the postoperative outcome of 100 primary breast augmentations. METHODS: A retrospective assessment of 100 consecutive primary breast augmentation patients over a period of 3 years was conducted. Patients were followed for a minimum of 6 months postoperatively. Demographics, surgical data, and complications were recorded. In addition, a survey regarding the breast augmentation outcome was performed. RESULTS: The reasons for surgery were mainly hypoplasia (52 percent) and ptosis (28 percent). All implants were placed by means of an inframammary approach in a submuscular pocket, and the average implant volume was 370 cc (range, 150 to 700 cc) with mostly full projection (65 percent). The revision rate was 7 percent. The authors observed four cases of implant malpositioning, one implant rupture, one implant exchange for aesthetic reasons, and one hematoma evacuation. Nevertheless, the authors achieved a 100 percent satisfaction rate with the postsurgical outcome among both patients and surgeons. CONCLUSIONS: Motiva Ergonomix implants provide reliable and satisfying results for both patients and surgeons. They can be used safely and effectively for aesthetic breast surgery. However, like all breast prostheses, Motiva Ergonomix implants are not completely free of complications and should be used only with advanced technique to achieve optimal results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 29794697 TI - Discussion: Motiva Ergonomix Round SilkSurface Silicone Breast Implants: Outcome Analysis of 100 Primary Breast Augmentations over 3 Years and Technical Considerations. PMID- 29794698 TI - Secondary Gluteal Augmentation: Surgical Technique and Outcomes. AB - BACKGROUND: As interest in posterior body contour has increased, there has been an upward trend in the number of gluteal augmentations performed. However, there has also been a proportional increase in postoperative complications and subsequent revision operations. Nevertheless, there are currently few studies or reports on secondary gluteal augmentation. The purpose of the present study was to identify methods to treat and prevent complications resulting from gluteal augmentation. METHODS: In this study, the authors review 18 cases of secondary gluteal augmentation. New intramuscular pockets were dissected more deeply than were previous pockets. Capsulotomy or capsulectomy was applied to the deep capsules of the previous pockets to sufficiently expand the new pockets and soft tissue to cover the implants. After triple-antibiotic irrigation, implants were inserted using the "no-touch technique." Next, "hybrid gluteal augmentation" was performed by grafting autologous fat into the subcutaneous fat layer. RESULTS: Among 18 cases of secondary gluteal augmentation performed, nine cases were performed by means of hybrid gluteal augmentation and seven cases were implant only augmentations. Postoperative complications occurred in two cases. One case involved the hybrid technique (remaining rippling), and the other case involved implant-only augmentation (implant palpability). However, there was no need for surgical correction. CONCLUSION: Secondary gluteal augmentation can be successfully performed using the hybrid technique if the gluteus maximus is accurately dissected, the capsules are appropriately managed, and infection is rigidly controlled. PMID- 29794699 TI - Three-Dimensional Printing in Rhinoplasty. AB - Rhinoplasty is considered one of the most challenging procedures in plastic surgery. The authors introduce a novel concept of translating three-dimensional photographic images into three-dimensionally-printed, patient-specific, life-size models that can be used in preoperative counseling or as an intraoperative reference during rhinoplasty. This article describes the authors' experience with this new application for three-dimensional printing, a technology that is overall garnering more widespread use and has prospective clinical and research applications in aesthetic surgery. PMID- 29794701 TI - Discussion: Innovative Surgical Approach Using a Mesh Sling for the Aging Neck. PMID- 29794700 TI - Innovative Surgical Approach Using a Mesh Sling for the Aging Neck. AB - BACKGROUND: Rejuvenation of the neck is essential to achieve a young facade. Different approaches for aging neck rejuvenation have been developed throughout the years. Most of them focus on specific elements that contribute to the aging neck. The main drawbacks of these techniques are recurrence of the platysma bands, malposition, deformations, salivary problems, and defatting. These disadvantages and limitations have led the author to create a novel surgical approach to improve the aging neck that would be suitable for most patients. Instead of dealing with each of the elements of the aging neck, the author's approach involves use of a sling to elevate all the descending elements as a whole to create a natural and longstanding result. METHODS: Since March of 2014, 10 patients have been operated on for neck lifting with this new approach. Four different types of material have been used: absorbable synthetic braided (Vicryl) in five patients, semiabsorbable synthetic braided and monofilament (Vypro) in one patient, absorbable synthetic matrix (TIGR) in three patients, and biological mesh-allograft material (AlloDerm) in one patient. Follow-up visits were made after 10 days, 3 months, 6 months, and annually. RESULTS: In all cases, the operations were uneventful. There were no major complications. Minor complication occurred in one patient with the Vypro mesh. The mesh caused stiffness and was replaced. Final aesthetic results were satisfactory in all cases. CONCLUSIONS: Current approaches for improvement of the aging neck do not fit all aging neck cases and are suitable for only a specific dominant element. The aging neck tends to reappear faster than expected because of recurrence or dominance of another element. The author's novel approach is more predictable and is suitable for most cases regardless of the dominant part causing the aging. More experience and longer follow-up are needed to choose the most appropriate material for the mesh. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 29794702 TI - Supportive Use of Adipose-Derived Stem Cells in Cell-Assisted Lipotransfer for Localized Scleroderma. AB - BACKGROUND: The authors aimed to analyze factors related to lipotransfer for localized scleroderma, and to explore the feasibility of cell-assisted lipotransfer for localized scleroderma treatment. METHODS: Abdominal fat samples were taken from six scleroderma patients without corticosteroid therapy, five scleroderma patients with corticosteroid therapy, and 10 normal liposuction patients. Their quantity, morphology, and proliferation ability were measured. Blood flow was measured by laser speckle contrast imaging in localized scleroderma lesions and normal contralateral regions for eight localized scleroderma patients. Bleomycin-induced skin fibrosis nude mice were also used to investigate differences between lipotransfer and cell-assisted lipotransfer. Fat weight was measured, and expression of transforming growth factor (TGF)-beta1 and type III collagen in the injected skin was determined by immunohistochemistry. RESULTS: The number of stem cells from scleroderma patients with corticosteroid treatment was significantly reduced. Mean blood perfusion in localized scleroderma lesions was not significantly different than in the contralateral normal regions. In normal nude mice, there were no significant changes in TGF beta1 and type III collagen between the control, lipotransfer, and cell-assisted lipotransfer groups, whereas in bleomycin-induced skin fibrosis nude mice, lipotransfer and cell-assisted lipotransfer reduced TGF-beta1 and type III collagen expression. CONCLUSIONS: For scleroderma patients, fewer adipose-derived stem cells, because of a history of corticosteroid therapy and a local inflammatory microenvironment, are more important factors, whereas blood supply showed no significant change. Therefore, cell-assisted lipotransfer not only improves the survival rate of transplanted fat but also improves skin texture in bleomycin-induced skin fibrosis nude mice. PMID- 29794703 TI - Disappearing Digits: Analysis of National Trends in Amputation and Replantation in the United States. AB - BACKGROUND: Significantly fewer replantations have been performed at the authors' institution in recent years, with similar trends observed across the United States. A study of three national databases was performed to evaluate this trend, its possible cause, and national health care implications. METHODS: The National Electronic Injury Surveillance System, Bureau of Labor Statistics, and National Inpatient Sample databases were queried for cases with a diagnosis of finger amputation over available years from 2000 to 2011. Data were weighted and analyzed to give appropriate national estimates of amputations, replantations, and related clinical variables. Trend analysis was performed using modified Poisson regression. RESULTS: Although workplace finger amputation rates decreased 40 percent from 2000 to 2010 (p < 0.0001), the overall finger amputation incidence did not change significantly (26,668 versus 24,215; p = 0.097). Compared with 930 replantations in 2001, only 445 were performed in 2011, more than a 50 percent decrease (p < 0.001). In all years, the majority of hospitals performing replantation performed only one (49.3 to 64.1 percent) each year, with a small minority (2.2 to 8.1 percent) performing more than 10 per year. In 2000, 120 hospitals (12.1 percent) performed at least one replantation, compared with only 80 hospitals (7.6 percent) in 2010, a 4.6 percent annual decline (p = 0.002). CONCLUSIONS: There has been a striking decline in digital replantations being performed, despite a relatively stable incidence of amputations. Apparently independent of declining work-related injuries, evolving clinical decision-making may be responsible for this trend. Decreasing replantation experience among hand surgeons lends credence to the development of specialized regional centers designed to treat these complex injuries. PMID- 29794705 TI - Discussion: Using Black Bone Magnetic Resonance Imaging in Craniofacial Virtual Surgical Planning: A Comparative Cadaver Study. PMID- 29794704 TI - Hand Surgeons Performing More Open Carpal Tunnel Releases Do Not Show Better Patient Outcomes. AB - BACKGROUND: Although previous studies have shown that more experienced surgeons have better patient outcomes following a variety of procedures, in hand surgery and carpal tunnel release in particular, this relation remains unproven. The authors assessed whether there is an association between surgeon volume and patient outcomes following open carpal tunnel release. METHODS: Patients who underwent carpal tunnel release between 2011 and 2015 at outpatient hand surgery clinics in The Netherlands were included. Surgeon annual volume was defined as the average number of carpal tunnel releases performed per year per participating surgeon over the study period. Primary outcome measures were the Symptom Severity Scale and Functional Status Scale of the Boston Carpal Tunnel Questionnaire 6 months postoperatively. Multilevel random intercept linear regression analyses were performed to assess whether there was an association between surgeon annual volume and outcome measures, with adjustment for patient characteristics, concomitant procedures, and intake score on the Boston Carpal Tunnel Questionnaire. RESULTS: A total of 1345 patients were included, operated on by 17 surgeons. Median annual surgeon volume was 75 (interquartile range, 50 to 149). Only 0.5 to 0.6 percent of the total variance in patient outcome on the Boston Carpal Tunnel Questionnaire could be explained by random differences between surgeons. The authors did not find an association between annual surgeon volume and outcome measures 6 months postoperatively (Symptom Severity Scale: beta = 0.000; 95 percent CI, -0.001 to 0.001; and Functional Status Scale: beta = 0.000; 95 percent CI, -0.001 to 0.001). CONCLUSION: In the authors' sample of highly specialized hand surgeons operating in high-volume centers, they found no differences in outcome between high- and low-volume surgeons. PMID- 29794706 TI - External Port Tissue Expansion in the Pediatric Population: Confirming Its Safety and Efficacy. AB - BACKGROUND: External filling ports in tissue expander-based reconstruction have the advantages of being associated with less pain and emotional distress. However, among practicing surgeons using tissue expansion, a theoretical concern remains regarding higher risk of infection. The authors' goal was to evaluate external port safety in the pediatric population by looking at the complications and overall success rate of reconstruction. METHODS: A retrospective review of all patients undergoing tissue expansion using external ports at Children's Hospital Los Angeles between January of 2008 and June of 2016 was conducted. Patient demographic and perioperative data were collected and analyzed. RESULTS: Two hundred forty-one expanders were placed in 100 pediatric patients, resulting in 123 procedures for congenital and acquired conditions, with an average age at the time of surgery of 7.1 years (range, 1 month to 19.9 years) and average follow-up length of 2.5 years (range, 2.8 months to 8.8 years). The overall complication rate was 29.9 percent, and the infection rate was 17 percent. The majority of these cases were treated conservatively without additional need for surgery. Of 123 cases, 25 required premature expander removal because of complications. Despite early intervention, 21 of these cases underwent successful completion of their reconstruction according to the preoperative plan, resulting in an overall 96.7 percent success rate of tissue expander reconstruction. CONCLUSIONS: In children, who are often less tolerant of the pain and distress associated with internal port expansion, the authors encourage the use of external ports. This study found a high success rate in terms of successful reconstruction, with the majority of complications being treated conservatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 29794707 TI - Discussion: External Port Tissue Expansion in the Pediatric Population: Confirming Its Safety and Efficacy. PMID- 29794708 TI - Differences in Common Orbital Blowout Fracture Sites by Age. AB - BACKGROUND: The purpose of this study was to compare orbital blowout fracture sites among different age groups. METHODS: This retrospective, observational, comparative study included 671 sides of 663 patients with an orbital blowout fracture. The authors classified patients into five groups based on age (childhood, 0 to 9 years; adolescence, 10 to 18 years; early adulthood, 19 to 44 years; middle adulthood, 45 to 64 years; and late adulthood, 65 years or older); causes of injury into five categories (i.e., sports, traffic accident, assault, fall, and others); and orbital blowout fracture sites into four regions [i.e., the orbital floor lateral (lateral floor) or medial to the infraorbital groove/canal (medial floor); the inferomedial orbital strut (strut); and the medial orbital wall (medial wall)]. RESULTS: A single medial floor fracture was observed in 70.3 percent of patients in the childhood age group. However, the proportion of patients with a single medial wall fracture or multiple fracture sites increased with age. A medial wall fracture was more common than a medial floor fracture in late adulthood. The distribution of orbital blowout fracture sites, the ratio of single or multiple fracture sites, and the causes of injury were statistically different among the age groups (p = 0.005, p = 0.003, and p < 0.001, respectively, Pearson chi-square test). CONCLUSIONS: Common orbital blowout fracture sites varied among age groups. These differences may be attributed to multiple factors, including differences in the morphology of the orbit and paranasal sinuses, composition of the facial bone, and causes of injury among age groups. PMID- 29794709 TI - Lymphovenous Anastomosis for the Treatment of Chylothorax in Infants: A Novel Microsurgical Approach to a Devastating Problem. AB - : With the expanding horizon of microsurgical techniques, novel treatment strategies for lymphatic abnormalities are increasingly reported. Described in this article is the first reported use of lymphovenous anastomosis surgery to manage recalcitrant chylothoraces in infants. Chylothorax is an increasingly common postoperative complication after pediatric cardiac surgery, with a reported incidence of up to 9.2 percent in infants. Although conservative nutritional therapy has a reported 70 percent success rate in this patient population, failed conservative management leading to persistent chylothorax is associated with a significant risk of multisystem complications and mortality. Once conservative medical strategies are deemed unsuccessful, surgical or radiologic interventions, such as percutaneous thoracic duct embolization or ligation, are often attempted. However, these procedures lack high-level evidence in the infant population and remain a challenge, given the small size of the lymphatic vessels. As such, we report our experience with performing lymphovenous anastomoses in two infants who had developed refractory chylothoraces secondary to thoracic duct injury following cardiac surgery for congenital cardiac anomalies. In addition, this article reviews the relevant pathophysiology of chylothoraces, current treatment algorithm following failed conservative management, and potential role of the microsurgeon in the multidisciplinary management of this life-threatening problem. As part of the evolving microsurgery frontier, physiologic operations, such as lymphovenous anastomosis, may have a considerable role in the management of refractory pediatric chylothoraces. In our experience, lymphovenous anastomosis can restore normal lymphatic circulation within 1 to 2 weeks, liberate patients from mechanical ventilation, and enable expeditious return to enteral feeding. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 29794710 TI - Discussion: Acellular Human Dermal Allograft as a Graft for Nasal Septal Perforation Reconstruction. PMID- 29794711 TI - Predictors of Patient Satisfaction and Postoperative Complications in Penile Inversion Vaginoplasty. AB - BACKGROUND: Penile inversion vaginoplasty is the current gold standard procedure for male-to-female transgender patients seeking gender-confirming genital surgery. Although complication data have been reported extensively in the literature, studies on patient-reported outcomes are sparse. This study aimed to report both postoperative complications and patient-reported outcomes from the largest cohort in the United States to date to undergo penile inversion vaginoplasty. Ultimately, the authors hoped to identify the predictors of postoperative complications and patient satisfaction. METHODS: A retrospective chart review of a single surgeon's experience with penile inversion vaginoplasty was performed from July of 2014 to June of 2016. Patient demographic data, postoperative complications, and patient-reported outcome data were collected. Data were correlated by binary logistic regression to determine predictors of postoperative complications and patient satisfaction. RESULTS: A total of 117 patients underwent penile inversion vaginoplasty. The most common complications were granulation tissue (26 percent), intravaginal scarring (20 percent), and prolonged pain (20 percent). Overwhelmingly, patients reported "feeling positively about their genitals" (94 percent) and "would do this operation again" (94 percent). Seventy-one percent of patients reported resolution of their gender dysphoria. The top predictors of patient dissatisfaction were intravaginal scarring, prolonged pain, excessive external scarring, loss of sensation, and hematoma/excessive bleeding. CONCLUSIONS: This is the largest study of penile inversion vaginoplasty in the United States to report on both postoperative complications and patient-reported outcomes. Despite moderate complication risk, patient satisfaction remains very high after penile inversion vaginoplasty, with the majority of patients reporting improvement of their gender dysphoria. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. PMID- 29794712 TI - Discussion: Predictors of Patient Satisfaction and Postoperative Complications in Penile Inversion Vaginoplasty. PMID- 29794713 TI - Understanding Patient Expectations of Lymphedema Surgery. AB - BACKGROUND: Patients with lymphedema refractory to medical treatment often have unrealistic expectations for lymphedema surgery. The purpose of this study was to assess patient expectations following lymphedema surgery. METHODS: Patients presenting to the clinic for initial evaluation for lymphedema surgery were offered to complete a survey designed to evaluate their expectations for limb appearance, limb function, and overall well-being following lymphedema surgery. The patients were instructed to score each item using a five-point scale for improvement. A mean expectation score was calculated, which was then used to estimate the effects of preoperative variables on patients expectations using multiple regression analysis. RESULTS: A total of 21 women and two men with a mean age of 60 years completed the survey. The upper limbs were affected in 10 patients and the lower limbs were affected in 13 patients. Physicians were the initial source of information about lymphedema surgery as a potential treatment option in 10 patients (43 percent), and a majority of the patients [n = 15 (65.2 percent)] thought that the physicians had fair or poor knowledge about lymphedema surgery. Significant or complete improvement was expected by 43.4 to 73.9 percent of patients. Patients' level of education, the disease duration, and the initial source of information about lymphedema surgery had a statistically significant impact on patients' expectations. CONCLUSIONS: Early data suggest that most patients learn about lymphedema surgery from nonphysicians, with many expecting complete or significant improvement of lymphedema-associated symptoms with surgery. These findings emphasize the importance of addressing patient expectations and providing appropriate counseling before surgery. PMID- 29794714 TI - Current Concepts in Orthognathic Surgery. AB - LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify skeletal differences that are treated with orthognathic surgery; describe the goals of orthognathic surgery; and understand modern virtual surgical planning of orthognathic movement of the mandible, maxilla, and chin. 2. Appreciate the surgical principles of maxilla- versus mandible-first surgery, and orthognathic surgery before orthodontic correction; and understand when an osseous genioplasty may be beneficial, and the potency of this bony movement. 3. Appreciate the utility of fat grafting as an adjunct to orthognathic bony movements, and demonstrate understanding of the utility of orthognathic surgery in the treatment of obstructive sleep apnea. 4. Be aware of associated complications and be able to critically assess outcomes following orthognathic surgery. SUMMARY: This CME article outlines the goals of orthognathic surgery, highlighting advances in the field and current controversies. The principles of the sequencing of osteotomies are discussed and literature is reviewed that may assist in decision-making as to maxilla-first versus mandible-first surgery. The emergence of "surgery first," in which surgery precedes orthodontics, is discussed and important parameters for patient candidacy for such a procedure are provided. The emerging standard of virtual surgical planning is described, and a video is provided that walks the reader through a planning session. Soft-tissue considerations are highlighted, especially in the context of osseous genioplasty and fat grafting to the face. The utility of orthognathic surgery in the treatment of obstructive sleep apnea is discussed. The reader is provided with the most current data on complications following orthognathic surgery and advice on avoiding such pitfalls. Finally, outcome assessment focusing on the most current trend of patient-reported satisfaction and the psychological impact of orthognathic surgery are discussed. PMID- 29794716 TI - Discussion: Gender Inequality for Women in Plastic Surgery: A Systematic Scoping Review. PMID- 29794715 TI - Gender Inequality for Women in Plastic Surgery: A Systematic Scoping Review. AB - BACKGROUND: Previous research has highlighted the gender-based disparities present throughout the field of surgery. This study aims to evaluate the breadth of the issues facing women in plastic surgery, worldwide. METHODS: A systematic scoping review was undertaken from October of 2016 to January of 2017, with no restrictions on date or language. A narrative synthesis of the literature according to themed issues was developed, together with a summary of relevant numeric data. RESULTS: From the 2247 articles identified, 55 articles were included in the analysis. The majority of articles were published from the United States. Eight themes were identified, as follows: (1) workforce figures; (2) gender bias and discrimination; (3) leadership and academia; (4) mentorship and role models; (5) pregnancy, parenting, and childcare; (6) relationships, work life balance, and professional satisfaction; (7) patient/public preference; and (8) retirement and financial planning. Despite improvement in numbers over time, women plastic surgeons continue to be underrepresented in the United States, Canada, and Europe, with prevalence ranging from 14 to 25.7 percent. Academic plastic surgeons are less frequently female than male, and women academic plastic surgeons score less favorably when outcomes of academic success are evaluated. Finally, there has been a shift away from overt discrimination toward a more ingrained, implicit bias, and most published cases of bias and discrimination are in association with pregnancy. CONCLUSIONS: The first step toward addressing the issues facing women plastic surgeons is recognition and articulation of the issues. Further research may focus on analyzing geographic variation in the issues and developing appropriate interventions. PMID- 29794717 TI - Antifibrinolytic Agents in Plastic Surgery: Current Practices and Future Directions. AB - BACKGROUND: Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The antifibrinolytic drugs tranexamic acid and epsilon aminocaproic acid have emerged as promising agents to reduce both perioperative blood loss and transfusion requirements. However, published reports in the plastic surgery literature are lacking. The authors sought to summarize the current knowledge of the use of antifibrinolytics in plastic surgery by reviewing the existing literature for clinical outcomes and recommendations. METHODS: A systematic review of the PubMed, Cochrane, and Google Scholar databases was conducted for publications examining the use of antifibrinolytics in plastic surgery. Studies were abstracted for procedure type, antifibrinolytic dose, time and mode of administration, blood loss, transfusion requirements, and complications. RESULTS: Thirty-three studies were deemed eligible for inclusion, comprising a total of 1823 patients undergoing plastic surgical procedures with tranexamic acid (n = 1328) and/or epsilon-aminocaproic acid (n = 495). CONCLUSIONS: Tranexamic acid and epsilon-aminocaproic acid are widely used to reduce blood loss and transfusion requirements in craniofacial and orthognathic surgery, without an increased risk of adverse events. Intravenous administration is most commonly used, although topical formulations show similar efficacy with a reduced systemic distribution. Tranexamic acid has also emerged as a promising agent in aesthetic surgery and burn care, due to its favorable safety profile and role in reducing blood loss, achieving an improved surgical field, and reducing edema and ecchymosis. Further investigation of these agents in the fields of burn care, aesthetic surgery, and microsurgery is warranted to standardize protocols for clinical use. PMID- 29794719 TI - Discussion: The Accuracy of Conflict-of-Interest Disclosures Reported by Plastic Surgeons and Industry. PMID- 29794718 TI - The Accuracy of Conflict-of-Interest Disclosures Reported by Plastic Surgeons and Industry. AB - BACKGROUND: The purpose of this study was to analyze the frequency and nature of self-reported conflict-of-interest disclosures in the plastic surgery literature and to compare these findings to the Physician Payments Sunshine Act database. METHODS: All articles published from August of 2013 through December of 2013 in four major plastic surgery journals were analyzed. For every publication, the conflict-of-interest disclosure statement for each investigator was reviewed. These statements were then compared to transactions of value for each investigator as reported by biomedical companies in the Sunshine Act database. An analysis was performed to identify and characterize specific factors associated with conflict-of-interest disclosures. RESULTS: A total of 1002 independent investigators/authors were identified. Of these, 90 investigators (9 percent) self-reported a conflict of interest. In contrast, a total of 428 authors (42.7 percent) were found to have received transactions of value from a biomedical company according to the Sunshine Act database. Conversely, a total of 22 authors (2.2 percent) self-reported a conflict of interest but were not found to have received transactions of value in the Sunshine Act database. Our analysis found that (1) academic investigators, (2) transactions of value in excess of $500, and (3) publishing articles related to the sponsoring biomedical company were all statistically associated with reporting conflicts of interest (p < 0.0001). CONCLUSIONS: Discordance exists between investigator/authors self-reporting in scientific journals and the government-mandated reporting of conflicts of interest by industry. Factors associated with conflict-of-interest disclosure include academic status, transaction amount, and article content related to the sponsoring biomedical company. PMID- 29794720 TI - Complacency, Conscience, and Complications. PMID- 29794721 TI - Macrotextured Breast Implants with Defined Steps to Minimize Bacterial Contamination around the Device: Experience in 42,000 Implants. PMID- 29794722 TI - Reply: Macrotextured Breast Implants with Defined Steps to Minimize Bacterial Contamination around the Device: Experience in 42,000 Implants. PMID- 29794723 TI - Orthognathic Surgery Has a Significant Effect on Perceived Personality Traits and Emotional Expressions. PMID- 29794724 TI - Successful Noninvasive Treatment of Festoons. PMID- 29794725 TI - Use of trastuzumab as an adjuvant/neoadjuvant therapy in patients with HER2 positive breast cancer in China: The Nvwa study. AB - The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use.This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I-III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses.Of 4994 HER2+ patients (mean age 51.1 +/- 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor.Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer. PMID- 29794726 TI - Low expression of long noncoding RNA MT1JP is associated with poor overall survival in gastric cancer patients: Protocol for meta-analysis. AB - BACKGROUND: Although several researches have investigated the association between development and metastasis of gastric cancer (GC) and the expression level of MT1JP, there are no consensuses about whether its expression is associated with overall survival (OS) and clinical feature for GC patients. METHODS: The databases including PubMed, EMBase databases, and the Cochrane Library were searched from inception to January 30, 2016, to identify the eligible studies. The quality of included studies was assessed according to reporting recommendations for tumor marker prognostic studies (REMARK). The association between expression level of LncRNA HOTAIR with OS for GC patients was assessed by calculating the pooled hazard ratio (HR) and 95% confidence interval (95% CI) using STATA version 12.0. Heterogeneity among studies will be assessed using the I statistic. RESULTS: Randomized controlled trials (RCTs), prospective cohort studies, and case-control studies will be used for the qualitative and quantitative synthesis of the meta-analysis to explore the association between MT1JP expression levels with OS for gastric cancer patients. CONCLUSION: We aim to draw an objective conclusion of the association between MT1JP expression levels with OS for gastric cancer patients. PMID- 29794727 TI - Therapeutic effects of various therapeutic strategies on non-exudative age related macular degeneration: A PRISMA-compliant network meta-analysis of randomized controlled trials. AB - PURPOSE: Age-related macular degeneration (AMD) is a chronic progressive central retinal disease. Geographic atrophy (GA) is a late stage of dry AMD (DAMD) and is a slowly but inexorably progressive disease that causes irreversible blindness over time. We aimed to assess various therapeutic strategies for DAMD and GA treatment by network meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) of atrophic AMD treatments published prior to December 16, 2017. Best-corrected visual acuity (BCVA) and change in GA area were evaluated to reflect therapeutic effects. A random-effects network meta-analysis, with a frequentist framework, was used to assess the effectiveness of therapeutic strategies for DAMD treatment. RESULTS: We included 22 articles that assessed 16 types of regimens and 2482 patients in our meta-analysis. The network meta-analysis results showed that zinc monocysteine (98.1%) was the most likely to improve BCVA (logMAR), followed by alprostadil (84.0%), eculizumab (70.5%), and rheohemapheresis (67.3%). In BCVA (letters) outcomes, rheohemapheresis (99.6%), lampalizumab (69.5%), and the antioxidant complex (67.9%) showed marked benefits in visual function recovery. Regarding the outcome of GA area change, isopropyl unoprostone (IU) (88.6%) might have the best GA area reduction; however, there was no significant difference between IU and the blank control. CONCLUSIONS: Zinc-monocysteine and rheohemapheresis showed significantly better effects on BCVA (logMAR) improvement, and compared with the blank control, rheohemapheresis and the antioxidant complex showed better effects on BCVA (letters) improvement. Other treatments have potential effects on DAMD, including alprostadil, eculizumab, and lampalizumab. However, there is no effective treatment for GA area reduction. PMID- 29794728 TI - Acute noncardiogenic pulmonary edema after neostigmine administration during the recovery period of general anesthesia: A case report. AB - RATIONALE: Acute non-cardiogenic pulmonary edema (ANPE) is a rare but challenging complication which occurs during the perioperative period, mainly before and after the extubation in the course of the recovery period of general anesthesia. It is characterized by increased fluid in extravascular pulmonary spaces, preventing gas exchange and further resulting in respiratory failure. PATIENT CONCERNS: A 12-year-old boy who had undergone island skin flap in the right upper limb and who developed a unilateral pulmonary edema after the administration of neostigmine during the recovery period of general anesthesia. The neostigmine was administered to reverse neuromuscular block. DIAGNOSES: Acute non-cardiogenic pulmonary edema. INTERVENTIONS: The patient was transferred to intensive care unit (ICU) and treated with mechanical ventilation (controlled mode ventilation pattern, CMV) and other supportive treatment. OUTCOMES: The oxyhemoglobin saturation of the patient returned to the normal level with symptoms and signs of ANPE significantly alleviated. The mechanical ventilation was withdrawn by the fourth day, and no sequela of vital organs was observed. LESSONS: Although neostigmine is widely used for recovery from neuromuscular block and exhibits satisfactory effect in most cases, there is a potential risk of ANPE in some cases, which is rare but potentially fatal and could affect the patient outcomes. Therefore, it is necessary for anesthetists to closely monitor the vital signs of patients after administration of neostigmine in the perioperative period. PMID- 29794729 TI - Limb-girdle muscular dystrophy type 2B misdiagnosed as polymyositis at the early stage: Case report and literature review. AB - RATIONALE: Dysferlin myopathy is an autosomal recessive hereditary muscular dystrophy due to deficiency of dysferlin caused by alteration of the DYSF gene; Limb-girdle muscular dystrophy type 2B (LGMD2B) is the most common in Its clinical phenotypes. However, LGMD2B is rarely seen in clinical cases and may initially present as weakness of proximalpelvis muscles and muscles in the posterior compartments of thighs,which will then cause difficulty in running and limping during walking. Laboratory tests at an early stage of the disease often indicate an increased level of serum creatine kinase (CK). Moreover, polymyositis (PM) is manifested as symmetrical proximal muscle weakness of the four limbs, accompanied by an increased level of serum CK. Thus, both are very difficult to identify in clinical practice. PATIENT CONCERNS: A 25-year-old woman was admitted to our department as the limb weakness progressively worsened. She began to experience proximal muscle weakness of both lower limbs without obvious inducement, which markedly increased when she climbed the stairs or stood up after squatting. Then her symptoms worsened, with difficulty in proximal and distal lifting of the lower extremities. DIAGNOSES: Through combined immunohistochemistry and Western-blot analysis, The patient was diagnosed with LGMD2B. INTERVENTIONS: There were symptomatic treatments such as coenzyme Q10. OUTCOMES: After symptomatic treatments, the patient's symptoms were obviously relieved, and the CK level decreased. LESSONS: Through this case, we found that combined application of immunohistochemistry and Western-blot analysis is helpful in early diagnosis of LGMD2B, and a new site of frame-shift mutation in the patient's DYSF gene was found. PMID- 29794730 TI - Pituitary resistance to thyroid hormone caused by a novel mutation (H435A) in the thyroid hormone receptor beta: A case report. AB - RATIONALE: In patients with pituitary thyroid hormone resistance, the ability of the pituitary gland to detect (and down-regulate) the increase of triiodothyronine is selectively impaired, while the periphery remains sensitive to triiodothyronine levels, producing symptoms of peripheral thyrotoxicity. Subsequently, there is no feedback of pituitary production of thyroid-stimulating hormone (TSH), which is responsible for this hyperthyroidism. PATIENT CONCERNS: We report a case of a 46-year-old Chinese woman diagnosed with a thyroid nodule, with normal thyroid function. She underwent conventional subtotal thyroidectomy, and replacement therapy (levothyroxine) was used for as convention. However, it was later proven that she had pituitary resistance to thyroid hormone, as supra physiological doses of levothyroxine were required to normalize TSH levels, which resulted in peripheral thyrotoxicity. DIAGNOSES: Based on the patient's symptoms, laboratory tests results, imaging examinations, and genetic analysis (which noted a gene mutation), a diagnosis of pituitary resistance to thyroid hormones was confirmed. INTERVENTIONS: The dose of levothyroxine was adjusted periodically and beta-adrenergic blocker was used as symptomatic treatment. OUTCOMES: The outcome in the reported case has been satisfactory despite the persistence of non suppressed TSH. LESSONS: An inappropriate level of TSH should always be evaluated. We found a new mutation (H435A) of the thyroid hormone receptor beta gene, which allowed for the establishment of a definitive diagnosis. PMID- 29794731 TI - An innovative thread-lift technique for facial rejuvenation and complication management: A case report. AB - RATIONALE: Aging of face is an unavoidable process. Traditional procedures for facial rejuvenation have multiple disadvantages. In this case report, we used an innovative technique combining thread lift with small incision rhytidectomy for facial rejuvenation. Management for complication was also reported. PATIENT CONCERNS: We presented a 52-year-old male with facial ptosis and wrinkles. DIAGNOSES: The patient was diagnosed as facial aging including skin laxity, mid face and mandibular jowl ptosis, static crows-feet wrinkles, and deepening nasolabial fold. INTERVENTIONS: We used an innovative technique combining thread lift with small incision rhytidectomy to treat facial aging. OUTCOMES: Improvements of the crow's feet, nasolabial fold, mid-face and lower face ptosis were observed. Complication of subcutaneous nodule was corrected with cosmetic effect of thread lift remained. LESSONS: The innovative technique combining thread lift with small incision rhytidectomy is a good alternative for the treatment of facial aging. PMID- 29794732 TI - Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit. AB - Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO: hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal >=40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0 7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3.8, P = .002), and at 72 hours (5.6 vs 4.3, P = .006). The symptom severity scores did not differ between the positive and normal LBT groups. A higher level of nausea was present in the H-SIBO group when compared to the M-SIBO group.Overall, the presence of SIBO does not affect SBT or CT at 24, 48, and 72 hours. However, when analyzing the subtypes, M-SIBO has significantly more delayed SBT and CT when compared to H-SIBO. These results suggest the presence of delayed motility in patients with high methane levels on LBT. PMID- 29794733 TI - Isolated interrupted of aortic arch diagnosed using CT angiography: A case report and literature review. AB - RATIONALE: Interrupted aortic arch (IAA) is defined as a complete luminal and anatomical interruption between the ascending and descending aortas. The majority of patients with IAA rarely reach adulthood. In most cases, IAA is associated with an intracardiac malformation, such as ventricular septal defect, bicuspidaortic valve, and patent ductus arteriosus. We reported a 70-year-old man with isolated IAA diagnosed using computed tomography angiography (CTA) without previous intervention. PATIENT CONCERNS: The patient presented with edema of the lower extremities and productive cough. DIAGNOSES: CTA displayed an interruption of the aortic arch distal to the left common carotid artery (type B) and extensive collateralization. INTERVENTIONS: The patient refused surgery and underwent conservative therapy with follow-up examinations because of the extensive collateral vascularization. OUTCOMES: The patient is still currently undergoing conservative therapy with follow-up examinations. LESSONS: IAA can present in adulthood with different clinical symptoms. Careful physical examination of the lower and upper peripheral pulses in adults with a chief complaint of hypertension is of outmost importance. CTA is a useful noninvasive imaging modality for the morphologic evaluation of aortic interruption and collateral circulation. PMID- 29794734 TI - Postoperative pulmonary complications and hospital stay after lung resection surgery: A meta-analysis comparing nonintubated and intubated anesthesia. AB - BACKGROUND: Since postoperative pulmonary complications are one of the main causes of morbidity and mortality in patients undergoing lung resection surgery, we performed a meta-analysis to compare the incidence of postoperative pulmonary complications and hospital death, and the length of hospital stay in patients who received nonintubated or intubated anesthesia during thoracoscopic surgery for lung resection and further explore the tricks in nonintubated anesthesia. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to September 2017. We included eligible research comparing nonintubated anesthesia with intubated anesthesia in thoracoscopic surgery for lung resection. The primary outcomes involved postoperative pulmonary complications, hospital death, and hospital stay. The rates and causes of conversion from nonintubated anesthesia to intubated anesthesia were also analyzed. RESULTS: After screening through 754 potentially relevant articles, we included 3 randomized controlled trials and 7 observational studies with 1138 patients. There was no perioperative mortality in 2 groups. The nonintubated group revealed comparable postoperative pulmonary complications (OR = 0.57; P = .07; P for heterogeneity = .49, I = 0%) and shorter hospital stay (WMD = -1.10; P < .00001; P for heterogeneity = .84, I = 0%) in overall findings with little heterogeneity. CONCLUSION: Nonintubated anesthesia in thoracoscopic surgery for lung resection shortened the length of hospital stay compared with intubated anesthesia. However, the incidence of postoperative pulmonary complications was comparable between nonintubated and intubated group. Given the potential perioperative emergencies, such as persistent hypoxemia, carbon dioxide retention, or extensive pleural adhesions, nonintubated anesthesia in lung resection surgery requires extra vigilance to ensure the safety of the patients and the success of the surgery. Powerful randomized controlled trials in the future are essential to provide more certainty and address long-term effectiveness. Only when anesthesiologists and surgeons make efforts together can better clinical outcomes in lung resection surgery be achieved. PMID- 29794735 TI - Diagnostic performance of magnetic resonance technology in detecting steatosis or fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. AB - BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of magnetic resonance (MR) imaging-based methods for detecting steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD). METHODS: Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area of operator receiver curve (AUROC), sensitivity and specificity of MR imaging, MR elastography, and MR spectroscopy in detecting or grading steatosis/fibrosis. Meta-analysis of correlation coefficients was performed to have an overall effect size of correlation between MR-based diagnosis and histological diagnosis. RESULTS: Twenty-one studies (1658 subjects; 45.32 years [95% CI: 35.94, 54.71] of age, 53.67% [45.39, 61.95] males, and 29.98 kg/m [21.93, 38.04] BMI) were included in the meta-analysis. Pooled analyses of the AUROC, specificity, and sensitivity values reported in the individual studies revealed an overall effect sizes of 0.90 (0.88, 0.92), 82.27% (77.74, 86.80), and 86.94% (84.18, 95.28) in the use of any MR-based technique for the diagnosis of NAFLD or its severity. The correlation coefficient between MR-based detection of liver steatosis and histologically measured steatosis was 0.748 (0.706, 0.789) (P < .00001). CONCLUSION: MRI-based diagnostic methods are valuable additions in detecting NAFLD or determining the severity of the NAFLD. PMID- 29794736 TI - Parotid gland metastasis from carcinoma of the breast detected by PET/CT: Case report and review. AB - RATIONALE: The parotid gland is an unusual site for metastatic disease from breast cancer, and it usually has a poor prognosis. PATIENT CONCERNS: A 36-year old woman presented to our department with a swelling in her left parotid gland. The patient did not receive any other treatment after breast conserving surgery. DIAGNOSES: Multifocal metastases in the bones, lymph nodes, left parotid and contralateral mammary gland were proved by PET/CT. INTERVENTIONS: Eight cycles of first-line rescue chemotherapy, combining with zoledronic acid in treatment of bone metastasis, followed by the combination of endocrine therapy and ovarian function suppression after chemotherapy. OUTCOMES: The patient obtained clinical complete response in the metastasis tumor of parotid gland, lymph nodes, and bones. LESSONS: It is necessary for patient to receive comprehensive treatment after receiving surgery. Through this case, we present the appropriate management of advanced breast cancer accompanying with the parotid gland metastasis. PET/CT is a useful method to diagnose and evaluate the metastasis lesions. PMID- 29794737 TI - Efficacy comparison between primary total laryngectomy and nonsurgical organ preservation strategies in treatment of advanced stage laryngeal cancer: A meta analysis. AB - BACKGROUND: We aimed to provide a pooled analysis of controlled trials comparing long-term survival after primary laryngectomy and primary organ preservation methods in patients with T3-4 laryngeal cancer. METHODS: We performed random effects meta-analyses on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional control (LRC). RESULTS: Fifteen studies met the selection criteria including 6288 patients (2696 patients who underwent primary laryngectomy and 3592 patients who underwent primary nonsurgical organ preservation therapy). There was a significant difference between the groups with respect to OS (HR 0.71, 95% CI 0.57-0.89, P = .003). However, a subgroup analysis found OS was not significantly worse for patients with T3 laryngeal cancer who received primary organ preservation compared with patients who underwent primary laryngectomy (HR 0.96, 95% CI 0.45-2.03, P = .91). There was no significant difference for DFS (HR 0.63, 95% CI 0.39-1.04, P = .07) in two groups. Patients with laryngeal cancer who underwent primary laryngectomy had a better DSS (HR 0.47, 95% CI 0.25-0.88, P = .02) and LRC (HR 0.56, 95% CI 0.390.80, P = .001) than patients who underwent primary nonsurgical organ preservation therapy. CONCLUSION: Our results support total laryngectomy for patients with T4 laryngeal cancer and show that primary organ preservation for laryngeal cancer has no advantage and also did not decrease the rate of OS in patients with T3 laryngeal cancer when compared with primary total laryngectomy. PMID- 29794738 TI - Exploring synergistic effects of aerobic exercise and mindfulness training on cognitive function in older adults: Protocol for a pilot randomized controlled trial. AB - INTRODUCTION: Despite increasing evidence that aerobic exercise and cognitive training improve cognitive function among patients with cognitive impairment and dementia, few studies have focused on the effect of a combination of these approaches. This study will explore whether combining aerobic training (AT) with mindfulness training (MT), an intervention promoting the moment-to-moment awareness of physical sensations, affective states, and thoughts, improves cognitive function in individuals at risk of dementia. The primary objective is to determine the feasibility and acceptability of the intervention(s). The secondary objective is to obtain estimates of effect sizes on cognitive function and on possible mediators. METHODS AND ANALYSIS: Forty participants with at least 2 risk factors for dementia will be randomized (2 * 2 factorial design) to either AT (3 sessions/week for 12 weeks), MT (1 session/week for 8 weeks), both, or usual care. Assessments of cognitive function (attention, executive function, episodic, and working memory); physical activity (accelerometry), aerobic capacity (6-minute walk test), waist-to-hip ratio, blood pressure, social support (Multidimensional Scale of Perceived Social Support), depression (Hospital Anxiety and Depression Scale), and mindfulness (Five Facets of Mindfulness) will be conducted at baseline, end of treatment, and 6-months postbaseline. Rates of retention, attendance, and program satisfaction will be calculated for each of the 4 groups to determine the feasibility and acceptability of each intervention. ETHICS AND DISSEMINATION: This study has full ethical approval by The Miriam Hospital Institutional Review Board and adheres to the Standard Protocol Items: Recommendations for Interventional Trials reporting recommendations. If results from this exploratory, proof-of-concept study support our hypotheses, we will conduct a large randomized controlled trial (RCT) to determine the efficacy of combined MT and AT in improving cognitive function in individuals at risk of dementia. Results from the study will be disseminated through peer-reviewed journals and conference presentations. REGISTRATION DETAILS:: http://www.clinicalstrials.gov identifier NCT03289546. PMID- 29794739 TI - Prevalence of chronic kidney disease-associated pruritus among adult dialysis patients: A meta-analysis of cross-sectional studies. AB - Chronic kidney disease (CKD)-associated pruritus is a common adverse symptom in patients with end-stage renal disease treated by dialysis. Herein, a systematic review and meta-analysis of the prevalence of CKD-associated pruritus among adult dialysis patients was conducted.An electronic search of PubMed, Web of Science, Elsevier, Wanfang, and Chinese National Knowledge Infrastructure databases was conducted from inception to November 23, 2016, and all cross-sectional studies that reported the prevalence of CKD-associated pruritus in dialysis were collected. The pooled prevalence was estimated by random-effects model. Potential publication bias was evaluated by the funnel plot as well as Begg and Egger tests.After rigorous screening, a total of 42 studies conducted on 11,800 patients were included in this study. The overall prevalence of CKD-associated pruritus among adult dialysis patients was 55% (95% confidence interval [CI], 49 61, I = 97.6%), the stratification of which was 55% (95% CI, 45-65, I = 94.7%) in men and 55% (95% CI, 46-65, I = 93.3%) in women. In hemodialysis (HD) patients, the prevalence of CKD-associated pruritus was 55% (95% CI, 49-62, I = 97.9%), while in peritoneal dialysis (PD) patients, it was 56% (95% CI, 44-68, I = 89.9%). The prevalence of CKD-associated pruritus for mean dialysis duration <40 months was 56% (95% CI, 48-63, I = 75.1%), while that for mean dialysis duration >=40 months was 50% (95% CI, 36-64, I = 99.1%).The prevalence of CKD-associated pruritus is high in HD and PD. The prevalence among adult dialysis patients is comparable between China and foreign countries as well as between females and males. Studies with the similar disease definition and analysis of the effects of risk factors on CKD-associated pruritus are needed. PMID- 29794740 TI - Prevalence of CD30 immunostaining in neoplastic mast cells: A retrospective immunohistochemical study. AB - Mastocytosis is a rare disease characterized by clonal neoplastic proliferation of mast cells (MCs). It ranges from skin lesions as cutaneous mastocytosis (CM) which may spontaneously regress to highly aggressive neoplasms with multiorgan involvement corresponding to some aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and/or mast cell sarcoma (MCS).There is increasing evidence of CD30 expression in neoplastic MCs of the bone marrow. This expression has been described almost exclusively in aggressive forms of systemic mastocytosis (SM).The aim of the present study is to evaluate CD30 expression both in cutaneous and systemic forms of mastocytosis. Forty-two mastocytosis cases were reviewed, including cutaneous (n = 29) and systemic (n = 13) forms to assess the prevalence of CD30 expression. Thirty-nine out of 42 (92.8%) cases were CD30 positive. In cases of CM, 28/29 (96.5%) cases were CD30 positive, 11/13 cases of SM (84.6%) were positive for CD30. MCs in normal skin biopsies and in urticaria lesions were CD30-negative. This study found that CD30 is also frequently expressed in CM as well as in systemic forms. This finding is a major departure from the prevailing concept that CD30 expression is often related to aggressive systemic forms of mastocytosis. PMID- 29794741 TI - Identification and analysis of key genes associated with ulcerative colitis based on DNA microarray data. AB - This study aimed to identify genes that may play a role in development of ulcerative colitis (UC) and gain insight into its pathogenesis.Gene expression profiling data, including samples collected from 13 early-stage UC (EUC), 8 advanced-stage UC (AUC), and 5 control subjects, were downloaded from the Gene Expression Omnibus database under the accession number of GSE9452. Differentially expressed genes (DEGs) were identified in EUC and AUC compared with controls. DEGs for EUC and AUC, as well as AUC-specific DEGs were subjected to pathway enrichment analysis. Random Walk with Restart (RWR) was used to identify DEGs that are critical in UC based on a protein-to-protein interaction (PPI) network and the inflammatory bowel disease (IBD) pathway downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. IL17 and transforming growth factor beta TGF-beta) expression levels in colonic tissue from patients with UC and normal colonic mucosa from healthy adults were analyzed by immunohistochemistry (IHC).A total of 3511 and 911 DEGs were identified in AUC and EUC, respectively. The overlapping DEGs and the AUC-specific DEGs were both enriched in pathways related to immunity, such as antigen processing and presentation. AUC-specific DEGs were related to cell migration, such as ECM receptor interaction. Following DEG prioritization, TLR4 and STAT1 were linked with EUC, AUC, and CD. The upregulated gene TGFB increased the number of Th17 cells, as verified by IHC. Furthermore, PIK3R1, CREBBP, and STAT1 were part of high-degree nodes in the PPI sub-network.The upregulated gene TGFB may regulate IL17 expression in UC. PIK3R1 may participate in immunity and CREBBP may interact with STAT1 in the development and progression of UC. PMID- 29794743 TI - Parietal complication of the hydatid disease: Comprehensive literature review. AB - BACKGROUND: The aim of the study was to provide an overview of the medical literature on parietal complications of hydatid disease (HD). METHODS: A literature search was conducted on PubMed, Medline, Google Scholar, and Google databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using keywords to identify articles related to parietal complications of HD in the thoracic and abdominal cavities. The following keywords were used: HD, hydatid cyst, cystic echinococcosis, alveolar echinococcosis, abdominal HD, thoracic HD, parietal complication, cutaneous fistulization, cystocutaneous fistulization, cutaneous involvement, external rupture, external fistulization, subcutaneous involvement, and subcutaneous abscess. The language of publication, journal, or country was not included as limitation criteria, and publications dated before August 1, 2016, were considered. Articles or abstracts containing adequate information, such as age, sex, cyst size, cyst location, clinical presentation, fistula opening location, and management were included in the study, whereas articles with insufficient clinical and demographic data were excluded. RESULTS: The literature review included 52 articles involving 55 patients with parietal complications of HD. Thirty-two articles were written in English, 15 in French, 2 in Spanish, 1 in Italian, 1 in German and 1 in Russian. All 55 patients (women, 30; men, 23; unknown, 2) involved in the study were aged 7 to 93 (mean +/- standard deviation, 54.5 +/- 20.2) years. A total of 24 patients had cysto-cutaneous fistula (Echinococcus granulosus), 12 had subcutaneous rupture, 10 had cutaneous fistula (E multilocularis), 3 had cystosubcutaneous abscess, 3 had cysto-cutaneo bronchial fistula, 2 had cysto-cutaneo-bronchio-biliary fistula, and 1 had cutaneo-bronchial fistula. E granulosus were detected in 43 and E multilocularis in 12 patients through clinical, radiological, or histopathological examinations. CONCLUSION: Parietal complications such as cysto-cutaneous fistulization are a rare complication of HD. Complicated HD should be considered in the differential diagnosis of patients presenting with cutaneous involvement, especially in HD endemic regions. PMID- 29794742 TI - Clinical impact of the alpha-galactosidase A gene single nucleotide polymorphism 10C>T: A single-center observational study. AB - Single nucleotide polymorphisms (SNPs) in the alpha-galactosidase A gene region (GLA) have been discussed as potential cause of symptoms and organ manifestations similarly to those seen in Fabry disease (FD). However, due to scarce data, clinical implications remain limited. The aim of the present study was to investigate the clinical impact of -10C>T SNP in the GLA.Prospective single center observational study to determine the natural history and outcome of FD.Subjects initially referred to the Fabry Center for Interdisciplinary Therapy Wurzburg (FAZIT) for management of suspected FD (11 women, 2 men, mean age 42 +/- 10 years) who were tested negative for coding GLA mutations but positive for the noncoding -10C>T SNP underwent comprehensive characterization for therapy recommendation.All subjects reported at least 1 neurological, but no cardiac or renal symptoms. In 7 patients, pain of unknown etiology was reported and 3 patients had a history of cryptogenic stroke. In all patients, alpha-GAL activity was at a lower limit, ranging between 0.27 and 0.45 nmol/min per mg protein (reference: 0.4-1.0), while plasma Lyso-Gb3 levels remained normal (range 0.39 +/ 0.33; reference: <=0.9 ng/mL). For both hemizygous subjects investigated, brain magnetic resonance imaging revealed unspecific white matter lesions. One of these subjects had suffered from severe early-onset stroke, the other showed mild hypertrophic cardiomyopathy.Presence of isolated heterozygous -10C >T SNP is not associated with clinically relevant symptoms or organ manifestations as seen in FD. Respective polymorphisms might, however, play a role in modifying disease severity in FD. Great care has to be taken in respective subjects suspected to suffer from nonclassical FD in order to prevent unnecessary Fabry-specific therapy. PMID- 29794744 TI - Post-radiotherapy maintenance treatment with fluticasone propionate and salmeterol for lung cancer patients with grade III radiation pneumonitis: A case report. AB - RATIONALE: This combination of fluticasone propionate (FP) and the long-acting beta2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6 degrees C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60 per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP. PMID- 29794745 TI - Study of the evolution and variability of nontraumatic orthopedic surgeries in Brazil-9 years of follow-up: A database study. AB - In Brazil, there are no epidemiological statistics that map nontraumatic orthopedic injuries, their rate of variability, distribution by specialty, fatality rate, and the economic impact that these lesions and their consequences can bring to the country. The objective of this study was to evaluate the rates of variability for skills, deaths, mortality, and the economic impact of nontraumatic orthopedic surgeries in Brazil from 2008 to 2016.This is a descriptive study conducted through the analysis of data relating to the indicators of hospital production regarding orthopedic procedures of the Department of Informatics of the Unified Health System (Departamento de Informatica do Sistema Unico de saude-DATASUS) between 2008 and 2016. The level of significance was 5%.There was a predominance of hospitalizations for surgery of the lower limbs, which also resulted in the largest number of deaths. The surgical mortality rate recorded for the hip also needs to be considered. In general, there is a national increase in the number of orthopedic surgeries performed, accompanied by a concomitant increase in the number of deaths and mortality of the population exposed.We observed a growing demand for hospitalization with a consequent increase in lethality and deaths. We can conclude that between 2008 and 2016, the number of hospitalizations for elective nontraumatic orthopedic surgical procedures increased significantly, driven mainly by lower limb surgeries, along with the cost of the Unified Health System (Sistema Unico de Saude-SUS) for these surgeries. PMID- 29794746 TI - Interpreting the various associations of MiRNA polymorphisms with susceptibilities of cardiovascular diseases: Current evidence based on a systematic review and meta-analysis. AB - BACKGROUND: To interpret the various associations between miRNA polymorphisms and cardiovascular diseases (CVD). METHODS: Literature search has identified relevant studies up to June 2016. A meta-analysis was performed followed the guidelines from the Cochrane review group and the PRISMA statement. Studies were identified by searching the Cochrane Library, EMBASE, PUBMED and WHO clinical trials registry center. A meta-analysis has been done with a fixed/random-effect model using STATA 14.0, which also has been used to estimate the publication bias and meta-regression. RESULTS: The results from 11 case-control studies were included. The miR-146a G/C makes a contribution to the causing of CVD as recessive genetic model. And the miR-499 G/A raised the risks of cardiomyopathy, however it could still accelerate the procedure of CVD combined with myocardial infraction. At this point, we consider that it could deepen the adverse of outcomes from coronary artery disease (CAD), but it's hard to draw an association between miR 499 G/A and CAD. At last the miR-196a2 T/C demonstrated a contrary role between development problem and metabolic issues, which protects the development procedure and impairs the metabolism to cause different disease phenotypes. CONCLUSION: Despite inter-study variability, the polymorphisms from miR-146a, miR 499 and miR-196a2 have impacts on cardiovascular disease. Each type of miRNA has individual role in either cardiac development or the origins of CVD. PMID- 29794747 TI - Tranexamic acid use during total hip arthroplasty: A single center retrospective analysis. AB - BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent that has shown promise in reducing blood loss during total hip arthroplasty (THA). Several studies have reported side effects of high-dose TXA administration, including myocardial infarction (MI), thromboembolic events, and seizures. These possible side effects have prevented the widespread adoption of TXA in the surgical community. METHODS: We conducted a retrospective chart review of 564 primary and revision THAs performed at a single academic center. Surgical patients received either no TXA or 1 g IV TXA at the beginning of surgery followed by a second bolus just before the surgical wound closure, at the surgeon's discretion. We analyzed differences in hemoglobin (Hb), hematocrit (Hct), estimated blood loss (EBL), and adverse events in patients receiving TXA versus patients not receiving TXA up to 2 days following surgery. RESULTS: Significantly higher Hb and Hct values were found across all time points among patients undergoing primary posterior or revision THA who had received TXA. In addition, transfusion rates were significantly decreased in both primary posterior THAs and revision THAs when TXA was administered. Patients who received TXA experienced significantly fewer adverse events than those who did not for all surgery types. CONCLUSION: Administration of low-dose intravenous (IV) and intra-articular (IA) TXA does not appear to increase rates of adverse events and may be effective in minimizing blood loss, as reflected by Hb and Hct values following THA. PMID- 29794748 TI - Study on body composition and its correlation with obesity: A Cohort Study in 5121 Chinese Han participants. AB - Rare reports can be found about sex- and age-specific body composition survey among Chinese population. The aim of this study is to explore the change of body composition with aging in Chinese males and females respectively.The present cross-sectional study was carried out in Central South University Xiangya School of Medicine Affiliate Haikou Hospital, on a random sample consisting of 5121 participants. Inbody720 body composition analyzer was used to detect the human body composition. Data collection was based on the assessment of anthropometric body composition measurements done with the help of bioelectric impedance. And the data were analyzed with SPSS19.0.We selected 5121 participants, 3276 males and 1845 females. A significant trend (P < 0.05) for all anthropometric indices was observed with age for both genders. Body fat in men and women were 18.33 kg and 19.82 kg, respectively. Body fat percentage in men and women were 25.74% and 34.01%, respectively. Visceral fat area in men and women were 91.98 cm and 77 cm, respectively And, with the increase of age, body fat, body fat percentages and visceral fat area also increased, both in men and in women. Meanwhile, with the increase of BMI, the body fat, body fat percentages, and visceral fat area also increased, both in men and in women.Significant trends were observed for body fat, body fat percentages and visceral fat area for both genders with age and both genders with BMI. Focusing on obesity-related lifestyle and prevent weight gain. PMID- 29794749 TI - The relationship of insulin resistance estimated by triglyceride glucose index and coronary plaque characteristics. AB - The triglyceride glucose (TyG) index is a useful surrogate marker for insulin resistance, which is an important risk factor for coronary artery disease (CAD). However, data on the relationship of the TyG index and coronary plaque characteristics are limited.This study included 2840 participants with near normal renal function who underwent coronary computed tomography angiography. CAD was defined as the presence of any plaques, and obstructive CAD was defined as the presence of plaques with >=50% stenosis. The relationship between the TyG index and noncalcified plaque (NCP), calcified or mixed plaque (CMP), and coronary artery calcium score (CACS) was evaluated.All participants were stratified into 4 groups based on the quartiles of the TyG index. The prevalence of CAD and obstructive CAD significantly increased with increasing quartiles. The risk for NCP and obstructive NCP was not different among all groups. However, compared with group I (lowest quartile), the risk for CMP was higher in groups III (odds ratio [OR]: 1.438) and IV (highest quartile) (OR: 1.895) (P < .05), and that for obstructive CMP was higher in groups II (OR: 1.469), III (OR: 1.595), and IV (OR: 2.168) (P < .05). Multivariate regression analysis showed that the TyG index was associated with an increased risk for CAD (OR: 1.700), obstructive CAD (OR: 1.692), and CACS >400 (OR: 1.448) (P < .05).The TyG index was independently associated with the presence and severity of CAD due to an increased risk for CMP. PMID- 29794750 TI - Management and outcomes of spinal epidural hematoma during vertebroplasty: Case series. AB - RATIONALE: Spinal cord injury (SCI) is one of the common complications of spinal surgery. There is no definite treatment and time of decompression for spinal cord induced by epidural hematoma during vertebroplasty. PATIENT CONCERNS: A total of 6 patients with SCI during vertebroplasty were included in our research. All of them occurred sensory disturbance and motor dysfunction due to a lower or same level operative vertebral body lesion in vertebroplasty. DIAGNOSES: Neurological manifestations during vertebroplasty, postoperative magnetic resonance imaging and computed tomography. INTERVENTIONS: Once SCI occurred in vertebroplasty, four patients were underwent spinal cord decompression immediately, and two patients were done after 14 and 22 hours, respectively. OUTCOMES: Before decompression operation, one patient was Frankel A, three were Frankel B, and two were Frankel C. One day after evacuation of the SEH, three patients recovered to normal neurological function (Frankel E), one to Frankel C, and one to Frankel D, but the other one did not recover. At the last follow-up, five patients had recovered to Frankel E and one patient to Frankel D. LESSONS: According to our experience, when SCI occurs during vertebroplasty, neurological deficits are always secondary to acute SEH. Timely decompression, particularly transfer surgery, can shorten recovery time. PMID- 29794751 TI - Pulmonary adenocarcinoma associated with Guillain-Barre syndrome: A case report. AB - RATIONALE: Guillain-Barre Syndrome (GBS) as a paraneoplastic manifestation of small cell lung cancer has been published several times, while paraneoplastic GBS accompanied by pulmonary adenocarcinoma is rare. PATIENT CONCERNS: An 80-year-old male was hospitalized with a 2-week history of fever and 10-day history of progressive ascending muscle weakness in the legs and arms. The patient felt weakness in legs at first when he was still able to move around, but the symptoms gradually progressed to the arms. At the time of office visit, he could no longer walk or hold up objects, and had absent deep-tendon reflexes as well as weakened left lung breath sounds. DIAGNOSES: Confirmed by the Cerebrospinal fluid (CSF) and electromyography examination, the patient was originally admitted into our hospital for GBS. However, radiology and histological examination revealed pulmonary adenocarcinoma. He was relatively old and confirmed to have pulmonary adenocarcinoma with simultaneously detected GBS, so was considered to be a paraneoplastic syndrome, rather than pure GBS. INTERVENTIONS: The patient was treated with methylprednisolone at 80 mg Qd for 10 consecutive days, which resulted in improvement in arms, then tapering to lower doses for 3 months. OUTCOMES: The patient showed temporary relief until relapse 6 months later, when the patient gave up treatment. LESSONS: To our knowledge, this is the first case of pulmonary adenocarcinoma that was diagnosed based on Guillain-Barre-like syndrome, which is very difficult to diagnose and treat. We suggest that elderly patients with GBS should not be considered as simple GBS and should be thoroughly examined to exclude systemic diseases, especially paraneoplastic neurological syndromes. In addition, the elderly should be screened regularly for tumor markers. PMID- 29794752 TI - Effects of abnormal 75 g oral glucose tolerance test at different time points on neonatal complications and neurobehavioral development in the pregnant women with gestational diabetes mellitus (a STROBE-compliant article). AB - With the improvement of living standard, gestational diabetes mellitus (GDM) incidence is increasing every year. We observed the effects of abnormal 75 g oral glucose tolerance test (OGTT) at different time points on neonatal complications and neurobehavioral development in GDM.A total of 144 newborns whose mothers were diagnosed with GDM and received prenatal examination and childbirth in our hospital from October 2015 to April 2016, were observed in this study. Pregnant women underwent 75 g OGTT and the blood glucose level was recorded on an empty stomach, as well as postprandial 1 and 2 hours, respectively. Based on the frequency of 75 g OGTT-abnormal time points, the pregnant women were divided into group 1 (OGTT abnormality at 1 time point), group 2 (OGTT abnormality at 2 time points), and group 3 (OGTT abnormality at 3 time points). Neonatal behavioral neurological assessment (NBNA) was performed on the 3 groups, respectively.In the total score of NBNA, there was a significant difference among the 3 groups (F = 17.120, P = .000), and there were significant differences between the 3 groups (all P < .05). The incidence of neonatal hypoglycemia was significantly lower in groups 1 and 2 than in group 3, and the incidence of macrosomia was significantly lower in groups 1 than in groups 2 and 3 (all P < .05). In the 144 newborns, NBNA scoring was significantly lower in the newborns with hypoglycemia than in the newborns with normal blood glucose level, and in macrosomia than in the newborns with normal body weight (all P < .01).With the increase of OGTT-abnormal time points in the pregnant women with GDM, the incidences of neonatal hypoglycemia and macrosomia rise and neonatal NBNA score decreases. Therefore, reasonable measures should be adopted as early as possible to prevent poor prognosis in the pregnant women with GDM. PMID- 29794753 TI - The predictive value and the correlation of peripheral absolute monocyte count, tumor-associated macrophage and microvessel density in patients with colon cancer. AB - The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral absolute monocyte count, tumor-associated macrophage, microvessel density, and to clarify the correlation between them in patients with colon cancer.A series of 216 patients with colon cancer were enrolled in this study. The peripheral absolute monocyte count was obtained from preoperative routine blood test. Tumor-associated macrophage and microvessel density were assessed on tissue microarray by immunohistochemistry.The one, three, five-year overall survival rate for the low absolute monocyte count group was 98.4%, 91.1%, 87.1%, respectively; and for the high absolute monocyte count group was 94.6%, 83.7%, 77.2%, respectively (P = .046). The one, three, five-year progression-free survival rate for the low absolute monocyte count group was 94.4%, 87.1%, 85.5%, respectively; and for the high absolute monocyte count group was 90.2%, 75.0%, 73.9%, respectively (P = .024). Univariate and multivariate analysis showed that there was a strong association between peripheral monocyte count and clinical outcome. The correlation between peripheral absolute monocyte count, tumor associated macrophage, and microvessel density were not observed.The peripheral absolute monocyte count was an independent prognostic factor for overall survival and progression-free survival in colon cancer. The high absolute monocyte count was significantly associated with poor outcome. PMID- 29794754 TI - A potentially new phase of the cardiac cycle: Pre-isovolumic contraction recognized by echocardiography. AB - Clinically the isovolumic contraction time (IVCT) can be measured by 3 echocardiographic methods of M-mode, pulse-wave Doppler (PWD), and tissue Doppler imaging (TDI). But IVCT can be clinically different by the 3 methods. This study is to investigate whether there is a potentially unidentified phase causing the discrepancies by analyzing electric mechanical delay time (EMD), IVCT, and pre ejection period (PEP).A total of 30 healthy subjects were recruited for the study. EMD, IVCT, and PEP were obtained by the 3 methods, respectively. MCT (the interval from the onset of the QRS wave to the closure point of the mitral valve measured by TDI) and ICMC (the interval from the onset of IVC wave S1 to the closure point of the mitral valve measured by TDI) were both measured by color TDI.IVCTt (IVCT measured by TDI) was significantly longer than IVCTm or IVCTd (IVCT measured by M-mode or PWD) (both P < .0001), while EMDt (EMD measured by TDI) was significantly shorter than EMDm or EMDd (EMD measured by M-mode or PWD) (both P < .0001). But MCT was not significantly different from EMDm or EMDd (P > .05) and ICMC did not differ significantly from EMDm or EMDd minus EMDt or IVCTt minus IVCTm or IVCTd (P > .05), in other words, ICMC almost equaled to (EMDm or EMDd minus EMDt) or (IVCTt minus IVCTm or IVCTd).There may be an unidentified phase between the end of atrial contraction and the closure of mitral valve causing the discrepancies in IVCT, which is named as the pre-isovolumic contraction phase. It is a non-isovolumic phase and is included in the traditional isovolumic contraction phase. PMID- 29794755 TI - Contrast-enhanced ultrasound findings of gallbladder adenocarcinoma with sarcomatoid carcinoma accompanied by intrahepatic metastasis: A case report and literature review. AB - RATIONALE: Gallbladder adenocarcinoma is the most common subtype of malignant tumor in gallbladder carcinoma; its incidence is quite low. Preoperative diagnosis of gallbladder adenocarcinoma appears to be very difficult because they are normally asymptomatic and are often found incidentally. Adenocarcinoma with sarcomatoid carcinoma of gallbladder is exceedingly rare with no case reported in the literature to date. PATIENT CONCERNS: A 69-year-old male was referred to our hospital due to right upper quadrant pain. To further diagnosis, he received laboratory tests, gray-scale US, and contrast-enhanced ultrasound (CEUS). In this present study, ethical approval was not necessary, as this article is a case report, which is based on the clinical information of the patient. The patient gave his permission for publication of the case. DIAGNOSES: Gray-scale abdominal ultrasound image demonstrated a hypoechoic intraluminal mass of gallbladder and a heterogeneous mass at the inferior segment of the right anterior liver lobe. In CEUS, the lesion of gallbladder was hyper-enhanced in the arterial phase, and hypo-enhanced in the later arterial phase. On liver, the hepatic lesion appeared heterogenous mild enhancement in the arterial phase. In portal and parenchymal phase, the hepatic lesion displayed hypo-enhancement, which conformed to the hepatic metastasis. INTERVENTIONS: The patient received cholecystectomy, right hepatectomy, and lymphadenectomy. OUTCOMES: He had an uneventful recovery from the procedure. LESSONS: We presented a case report with gallbladder adenocarcinoma with sarcomatoid carcinoma accompanied by intrahepatic metastasis, focusing on the ultrasound imaging features of this tumor, especially its enhancement pattern on CEUS. CEUS provided helpful information for diagnosis. Herein, we report the case; and the associated literature is further reviewed. PMID- 29794756 TI - Medial gastrocnemius structure and gait kinetics in spastic cerebral palsy and typically developing children: A cross-sectional study. AB - To compare medial gastrocnemius muscle-tendon structure, gait propulsive forces, and ankle joint gait kinetics between typically developing children and those with spastic cerebral palsy, and to describe significant associations between structure and function in children with spastic cerebral palsy.A sample of typically developing children (n = 9 /16 limbs) and a sample of children with spastic cerebral palsy (n = 29 /43 limbs) were recruited. Ultrasound and 3 dimensional motion capture were used to assess muscle-tendon structure, and propulsive forces and ankle joint kinetics during gait, respectively.Children with spastic cerebral palsy had shorter fascicles and muscles, and longer Achilles tendons than typically developing children. Furthermore, total negative power and peak negative power at the ankle were greater, while total positive power, peak positive power, net power, total vertical ground reaction force, and peak vertical and anterior ground reaction forces were smaller compared to typically developing children. Correlation analyses revealed that smaller resting ankle joint angles and greater maximum dorsiflexion in children with spastic cerebral palsy accounted for a significant decrease in peak negative power. Furthermore, short fascicles, small fascicle to belly ratios, and large tendon to fascicle ratios accounted for a decrease in propulsive force generation.Alterations observed in the medial gastrocnemius muscle-tendon structure of children with spastic cerebral palsy may impair propulsive mechanisms during gait. Therefore, conventional treatments should be revised on the basis of muscle-tendon adaptations. PMID- 29794757 TI - Correlation between oral health and quality of life among the elderly in Southwest China from 2013 to 2015. AB - The aim of this study was to evaluate the oral health among the elderly in Southwest China and to analyze the correlation between common oral diseases and quality of life (QOL) in the same population, thus providing recommendations to improve their oral health and life quality.Elderly people (>60 years' old) were randomly recruited into our study, and we performed oral health examinations and diagnoses, using the Community Periodontal Index (CPI) to assess the periodontal condition, and Oral Health Impact Profile-14 (OHIP-14) to score life quality associated with oral health. Then we analyzed correlations between oral health and QOL as well as body mass index (BMI).A total of 687 subjects participated in our study and 212 (30.9%) were diagnosed with gingivitis or subgingival calculus, 291 (42.4%) with moderate chronic periodontitis, 136 (19.8%) with severe chronic periodontitis, 514 (74.8%) with dental caries, and 648 (94.3%) with dentition defects. A total of 653 (95.1%) qualified OHIP-14 scores were collected, with a median score of 13. The scores of the severe and moderate periodontitis were similar to the dentition defects, but higher than the scores for gingivitis and subgingival calculus. Considering the most common side effect, 11% of the subjects with severe chronic periodontitis were reported to be "unsatisfied with eating," and 48.4% of the participants with dentition defects complained about "troubles with pronunciation." A logistic regression analysis revealed that underweight (BMI <20) correlated with dental caries (odds ratio [OR]: 0.167, P = .040) and dentition defects (OR: 0.119, P = .016).The general oral health condition was poor among the elderly in Southwest China. Periodontitis and dentition defects have considerable negative effects on the QOL among this population. PMID- 29794758 TI - Comparison of standard-dose 3-weekly cisplatin and low-dose weekly cisplatin for concurrent chemoradiation of patients with locally advanced head and neck squamous cell cancer: A multicenter retrospective analysis. AB - Standard treatment for locally advanced (stage III-IV) head and neck squamous cell cancer (LA-HNSCC) is concurrent chemoradiation therapy (CCRT) with cisplatin 100 mg/m every 3 weeks. For medically unfit patients susceptible to treatment related adverse events, low-dose weekly cisplatin (30-40 mg/m) can be used as an alternative. In this study, we retrospectively compared the therapeutic outcomes of low-dose weekly cisplatin regimen and standard regimen in CCRT for LA HNSCC.The medical records of histologically confirmed LA-HNSCC patients were retrospectively reviewed from January 1, 2007 to December 31, 2012. Patients who were treated with CCRT as initial treatment were included.Among 220 patients eligible, 65 (29.5%) were treated with cisplatin dosing schedule of 100 mg/m every 3 weeks and 155 (70.5%) with 30 to 40 mg/m weekly. The overall response rate in 3-weekly group was 92.3% and did not differ from that in weekly group (91.0%). The median progression-free survival of the weekly group was not attained but was not significantly different from that of 3-weekly group (50.7 months, 95% confidence interval [CI] 42.2-59.1 months) (P = .81). Also, the median overcall survival did not differ significantly between 2 groups (P = .34).In the present study, low-dose weekly cisplatin showed therapeutic outcomes comparable to standard-dose cisplatin in CCRT for LA-HNSCC. Prospective comparison of standard-dose three-weekly and low-dose weekly cisplatin is warranted. PMID- 29794759 TI - Comparison of the effectiveness in pain reduction and pulmonary function between a rib splint constructed in the ER and a manufactured rib splint. AB - BACKGROUND: In the treatment of patients with rib fractures (RFs), pain reduction is the most important consideration. Various studies have examined the effectiveness of treatments administered to RF patients, such as lidocaine patches, IV drugs, nerve blockers, and surgery. In this study, we evaluated the difference in the effectiveness in pain reduction between 2 groups of RF patients: 1 group who received a rib splint constructed in the ER (ER splint) and another group who received a Chrisofix Chest Orthosis (CCO) manufactured rib splint. METHODS: A pilot study for a prospective randomized clinical trial was conducted to compare subjects using the CCO (Group A) with those using the ER splint (Group B) before and after the intervention. The primary outcome was difference in the level of pain based on the visual analogue scale (VAS) and the pulmonary function (PF) variables between before and after intervention in each group during forceful and resting respiration. RESULTS: A total of 24 subjects were enrolled in this study. The VAS results showed that the intervention was significantly effective in each group (before vs after: Group A resting: 8.50 +/- 1.05 vs 4.17 +/- 1.33, P < .001; Group A forceful: 9.83 +/- 0.41 vs 7.17 +/- 0.75, P < .001; Group B resting: 8.83 +/- 1.60 vs 4.50 +/- 1.38, P < .001; and Group B forceful: 9.67 +/- 0.82 vs 7.33 +/- 1.51, P = .003). The PF variables showed that the intervention was significantly effective in each group (before vs after: Group A, FVC: 2.74 +/- 0.92 vs 3.35 +/- 0.99, P < .001; FEV1: 2.16 +/- 0.74 vs 2.57 +/- 0.78, P = .001; PEF: 235.30 +/- 43.06 vs 319.00 +/- 51.58, P = .004; and Group B, FVC: 2.02 +/- 0.49 vs 2.72 +/- 0.62, P < .001; FEV1: 1.27 +/- 0.25 vs 1.91 +/- 0.37, P < .001; PEF: 216.67 +/- 67.49 vs 300.33 +/- 87.79, P = .003). CONCLUSION: Applying either the CCO or the ER splint to RF patients effectively reduced pain, and no significant differences in pain level were observed between these 2 techniques. PMID- 29794760 TI - A five year CT surveillance of ciliated retroperitoneal foregut cyst resembling a cystic pancreatic lesion: A case report. AB - INTRODUCTION: Ciliated retroperitoneal foregut cysts are rare, and to obtain a preoperative definitive diagnosis of this condition is relatively difficult. In addition, the exact mechanism and formation of ciliated retroperitoneal foregut cysts remains unknown. CASE PRESENTATION: Here, we report a case of a 47-year-old woman who presented with an unusual shaped cystic lesion associated with a patch of solid components between the pancreas and the left kidney, initially misdiagnosed as a cystic pancreatic lesion 5 years previously to presentation at our clinic. During the past years, reports relating to the surveillance of these lesions described that their shapes progressively change while its volumes remain invariably unchanged. We did not observe this phenomenon in any literatures to our knowledge. The patient was diagnosed with ciliated retroperitoneal foregut cyst with remote hemorrhage, after the laparoscopic surgery. CONCLUSIONS: Ciliated retroperitoneal foregut cysts have characteristic manifestations. From this case, we summarized that cysts in the retroperitoneum, associated with a changing shape of the lesion, highly suggest the diagnosis of foregut cysts, which are safe under long-term surveillance. PMID- 29794763 TI - Enteritis as initial manifestation of systemic lupus erythematosus in early pregnancy: A case report: Erratum. PMID- 29794761 TI - Efficacy and safety of thread embedding acupuncture combined with conventional acupuncture for chronic low back pain: A study protocol for a randomized, controlled, assessor-blinded, multicenter clinical trial. AB - BACKGROUND: Back pain is one of the most common diseases, and many patients with recurrent pain seek alternative treatment strategies. Thread embedding acupuncture involves thread insertion at the acupuncture point for continuous physical and chemical stimulation. Although thread embedding is widely used in clinical practice, there is no sound evidence of its efficacy for chronic back pain. We describe the protocol for a randomized controlled trial for investigation of the efficacy and safety of thread embedding acupuncture combined with conventional acupuncture for chronic low back pain. METHODS: This randomized, controlled, assessor-blinded, 2-armed, parallel, multicenter clinical trial will include 38 outpatients with chronic low back pain recruited from 4 traditional Korean Medicine hospitals. The patients will be randomly allocated to a treatment group (conventional acupuncture + thread embedding acupuncture) and a control group (only conventional acupuncture) in a 1:1 ratio. The treatment group patients will receive thread embedding acupuncture treatment at 10 acupuncture points (multifidus muscle, 4 points; spinal erector muscles, four points; lumbar quadrate muscle, 2 points) once a week for 8 weeks (8 sessions). In addition, all patients will receive conventional acupuncture treatment at 14 acupuncture points (GV3, EX-B5, and bilateral BL23, BL24, BL25, BL26, BL40, and BL60) twice a week for 8 weeks (16 sessions). The primary outcome will be the change in the visual analog scale score from visit 1 to visit 16, analyzed by independent t tests, in both groups. The groups will also be compared with regard to the clinical relevance (minimal clinically important difference), quality of life (3-level version of Euroqol-5D), disability level (Roland and Morris Disability Questionnaire), global assessment (patient global impression of change), and safety. Cost data for cost-benefit and cost-effectiveness analyses will be collected. DISCUSSION: Our study results will provide evidence of the efficacy and safety of thread embedding acupuncture combined with conventional acupuncture for the management of chronic low back pain. Even though the assessors will be blinded, the patients will not be blinded to treatment because of the lack of a sham embedding acupuncture group; this is a limitation of our study. TRIAL REGISTRATION: Clinical Research Information Service: KCT0002666. PMID- 29794762 TI - Successful treatment of multisite hemorrhage by several methods in brain metastasis of choriocarcinoma: A case report. AB - RATIONALE: Brain metastasis of choriocarcinoma is a highly malignant gestational trophoblastic neoplasia (GTN) and has a notoriously poor prognosis. Hemorrhagic choriocarcinoma lesions may lead to life-threatening conditions also. Treatment of brain metastases of choriocarcinoma with hemorrhage in multiple sites is very difficult in clinical practices. A patient has been successfully treated in our hospital, which provides as clinical references for this difficulty in treating brain metastases of choriocarcinoma with hemorrhage in multiple sites. PATIENT CONCERNS: A 28-year-old patient with gravida 2, para 0 was admitted in our hospital for amenorrhea, vaginal bleeding, and lower abdominal pain. DIAGNOSES: The patient was diagnosed as choriocarcinoma FIGO stage IV and the score of the Prognostic Scoring Index modified by the WHO was 15. INTERVENTIONS: The patient received multiagent chemotherapy (EMACO regimen) soon after the diagnosis of choriocarcinoma with brain metastasis. During the therapy, the patient was given 3 different methods of treatment for metastatic site hemorrhage. An emergency surgery was performed to control massive bleeding from the metastatic lesions of broad ligament. Blood transfusions were given to treat acute left pulmonary hemorrhage. Uterine artery embolization (UAE) was performed to treat increased uterine bleeding. OUTCOMES: The patient achieved remission after 9 cycles of chemotherapy. She has been followed up for 14 months with no signs of tumor recurrence. LESSONS: The diagnosis of choriocarcinoma may be difficult, especially in the setting with the limit of medical resources. The application of various diagnostic techniques such as x-ray, computed tomography, and magnetic resonance imaging is helpful for evaluating the patient's condition. PMID- 29794764 TI - Gender difference in long-term use of opioids among Taiwan officially registered patients with chronic noncancer pain. AB - Research regarding sex or gender difference in chronic pain proliferated in this decade. This study was to analyze gender difference in Taiwan patients receiving long-term opioids for chronic noncancer pain.An observational cross-sectional survey was conducted among the registered outpatients by the Taiwan Food and Drug Administration. Participants completed a self-report questionnaire, including the Taiwanese version of Brief Pain Inventory and enquiry regarding sexual activities, depressive symptoms, and misuse behaviors.In total, 68 female and 142 male patients were analyzed. Both pain intensity and daily function interference reduced comparably (around 50%) between women and men after taking opioids in the past 1 week. The opioid-related adverse effects, including constipation, decreased sexual desire and satisfaction, and misuse behaviors were not significantly different. Women were exceedingly diagnosed with depression (67.7% vs 49.3%, P = .012) and had a higher mean depressive symptom score in the past 1 month, especially among those age <40 years (23.3 vs 11.9, P = .009), as compared with men. In addition, women had a lower mean self-rated health score (37.9 vs 44.3, P = .047). The mean morphine equivalent dose was significantly lower in women (131.6 vs 198.2 mg/day, P = .008), which was not correlated with their depressive scores.Gender differences in the effectiveness and adverse effects of long-term opioids were not found among Taiwan registered outpatients with chronic noncancer pain. However, more female patients inclined to have a coexisting depression diagnosis, depressive symptoms, and a lower perceived health score, needing regular screening and closer monitoring. PMID- 29794766 TI - Multiple intracranial lesions as the unusual imaging features of Hashimoto's encephalopathy: A case report. AB - RATIONALE: Hashimoto's encephalopathy (HE) is associated with autoimmune thyroid disease and is complex, diverse, and easily misdiagnosed. However, if HE is diagnosed and treated in a timely manner, an optimal prognosis may be achieved. PATIENT CONCERNS: We presented a case of a 63-year-old female patient with paroxysmal dizziness, unsteady gait, emotion apathy, progressive cognitive impairment, and unusual magnetic resonance imaging (MRI) findings. DIAGNOSES: After suffering for almost 8 years, the patient was diagnosed with HE based on clinical manifestation, abnormal electroencephalogram, unusual MRI findings, sensitivity to cortisol treatment, and characteristic high antithyroid peroxidase antibody (TpoAb) titer. INTERVENTIONS: The patient continued regular glucocorticoids therapy after intravenous methylprednisolone pulse therapy, neurotrophic drugs, traditional Chinese medicine and rehabilitation to relieve hypermyotonia and cognitive impairment. OUTCOMES: After combined treatment, the patient's symptoms, electroencephalogram (EEG), MRI, and the TpoAb titer gradually improved. However, the patient had to stop glucocorticoids treatment because of severe osteoporosis, fractures and other adverse reactions. Her symptoms fluctuated, and her TpoAb titer increased again. LESSONS: HE may cause highly heterogeneous clinical features, particularly MRI findings. Withdrawal of the systematic glucocorticoids treatment can lead to varied outcomes in these patients. PMID- 29794765 TI - Efficacy and safety of Kangfuxin liquid combined with aminosalicylic acid for the treatment of ulcerative colitis: A systematic review and meta-analysis. AB - BACKGROUND: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC). METHODS: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool. RESULTS: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RR = 1.19, 95% CI: (1.16, 1.23), P < .00001], reduced the relapse rate [RR = 0.26, 95% CI: (0.18, 0.38), P < .00001], reduced the inflammation factor levels of TNF-a, IL-1, IL-6, IL-8, and C-reactive protein, reduced the coagulation index of fibrinogen, increased the coagulation index of prothrombin time, and mean platelet volume, and reduced the clinical symptoms of abdominal pain, diarrhoea, pus and bloody stool, and tenesmus. However, KFXL combined with ASA did not increase the adverse event incidence [RR = 0.74, 95% CI (0.42, 1.32), P = .31], and no severe adverse events were reported. CONCLUSION: KFXL combined with ASA has good therapeutic effect for UC and might be a safe approach in managing UC. More high-quality, multicenter randomized, double-blind trials with a large sample size are required to generate a high level of clinical evidence. PMID- 29794767 TI - Thyroid follicular carcinoma-like renal tumor: A case report and literature review. AB - RATIONALE: Thyroid follicular carcinoma-like renal tumor (TFCLRT) is a rare primary renal epithelial tumor that was first reported in 2006. We report a case diagnosed of TFCLRT by us to observe the pathological feature and analyze comparatively the clinical and pathologic characteristics with all cases of reviewed literatures. PATIENT CONCERNS: A 54-year-old female patient had the urinary frequency with the symptom of right flank pain with a history of more than half a year of hypertension and received uterine fibroid resection 12 years ago. B-mode ultrasound examination and renal magnetic resonance showed a right renal sinus nodule. DIAGNOSES: Histopathology revealed thyroid follicle-like structures of different sizes, containing a colloid-like substance, while the periodic acid-Schiff (PAS) and diastase-resistant PAS staining confirmed that it was mucus protein. Immunohistochemical staining showed that it expresses the transcription factor PAX-8 but does not express the thyroid-specific antibodies TG and TTF-1. INTERVENTIONS: The patient underwent a tumor enucleation of right kidney. No other treatment was conducted after surgery. OUTCOMES: No metastases to lymph nodes and other organs were found, and 9-months of follow-up did not reveal any tumor progression. LESSONS: We should differentially diagnose the renal metastasis of thyroid follicular carcinoma or papillary carcinoma. Some related literatures reported that the tumour cells had significant heteromorphism, several of which metastasized to lymph nodes or distal organs. Its biological behavior need to be studied intensively by further expanding the number of cases. PMID- 29794768 TI - Clinical characteristics and functional status of children with different subtypes of dyskinetic cerebral palsy. AB - Dyskinetic cerebral palsy (CP) is the second major subtype of CP. Dyskinetic CP can be classified into different subtypes, but the exact clinical characteristics of these subtypes have been poorly studied. To investigate the clinical characteristics and functional classification of dyskinetic CP from the perspective of neurologic subtypes in a hospital-based follow-up study.This was an observational study of consecutive children with dyskinetic CP treated at The Affiliated Women & Children Hospital of Qingdao University (China) from October 2005 to February 2015. The children were stratified according to their neurologic subtype and assessed with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS). MRI scanning was conducted at 1 year of age for most children.Twenty-six participants (28.0%) had dystonic CP, 26 (28.0%) had choreoathetotic CP, and 41 (44.1%) had mixed CP. Auditory impairment and basal ganglion lesions occurred more frequently in the dystonia group (n = 8, 31%; and n = 16, 67%), while seizures, microcephaly, white matter lesions, and mixed lesions were more frequent in the mixed type (n = 14, 34%; n = 10, 24%; n = 15, 41%; n = 12, 32%). Functional classification levels were distributed unequally among the 3 subgroups (P < .01). No significant difference between GMFCS and MACS was found among the 3 subgroups (P > .05).Different subtypes of dyskinetic CP have specific comorbidities, radiological characteristics, and functional attributes according to their etiological factors and brain lesions. Children with dystonic CP have more limited functional status than children with choreoathetotic CP. PMID- 29794769 TI - Nonoperative manipulative reduction with Chinese herbs for the treatment of a displaced olecranon fracture: A case report. AB - RATIONALE: Displaced olecranon fracture is a common injury following a fall or direct trauma to the elbow. There have been no reports of patients with a displaced olecranon fracture who have only received nonoperative manipulative reduction with Chinese herbs. PATIENT CONCERNS: The patient was a 64-year-old woman with a complex elbow injury that occurred in a traffic accident. The patient complained of severe, painful limitation of motion on straightening or bending. DIAGNOSES: The patient was diagnosed with a displaced fracture of the left olecranon (type IIA olecranon fracture according to the Mayo classification system). INTERVENTIONS: The patient underwent nonoperative manipulation with Chinese herbs. OUTCOMES: The fracture was successfully reduced. After 3 to 4 months of follow-up, severe pain and disability in the elbow were improved following reduction of the left olecranon fracture in which there was no longer a displacement. LESSONS: Nonoperative manipulative reduction performed by a well trained physician with Chinese herbs may be a treatment option for displaced olecranon fractures. PMID- 29794770 TI - Traumatic fractures resulting from collisions in children and adolescents: A retrospective observational study. AB - To investigate the incidence and pattern of child and adolescent (<=18 years old) traumatic fractures (TFs) as a result of collisions.We retrospectively reviewed 270 child and adolescent patients (228 males and 42 females aged 12.8 +/- 5.1 years old) with TFs as a result of collisions admitted to our university affiliated hospitals from 2001 to 2010. The incidence and patterns were summarized with respect to different age groups, sex, etiology, and whether the patient presented with nerve injury.The most common etiologies were struck by object (105, 38.9%) and wounded by person (74, 27.4%). The most common fracture sites were upper limb fractures (126, 46.7%) and craniofacial fractures (82, 30.4%). A total of 65 (24.1%) patients suffered a nerve injury. The frequency of early and late complications/associated injuries was 35.6% (n = 96) and 8.5% (n = 23), respectively. The mean age (P = .001) and frequency of wounded by person (P = .038) was significantly larger in male than in female patients. The frequency of earthquake injury (P < .001) and lower limb fractures (P = .002) was significantly larger in females than in male patients. The frequency of upper limb fracture was significantly higher in the wounded by machine group (83.3%) than in the other groups (all P < .05). The frequency of lower limb fractures was significantly higher in the earthquake injury group (64.7%) than in the other groups (all P < .05). The frequency of craniofacial fracture was significantly higher in the wounded by person group (54.1%) than in the other groups (all P < .05). The emergency admission rate (P = .047), frequency of wounded by person (P < .001), craniofacial fracture (P < .001), and early complications/associated injuries (P < .001) were significantly larger in patients with nerve injury than in other patients.Struck by object and upper limb fractures were the most common etiology and site, respectively. Wounded by person and craniofacial fractures were risk factors for nerve injury. Therefore, we should pay more attention to patients wounded by person, presenting with craniofacial fracture, to find whether there is nerve injury. PMID- 29794771 TI - Function scores of different surgeries in the treatment of knee osteoarthritis: A PRISMA-compliant systematic review and network-meta analysis. AB - BACKGROUND: Osteoarthritis (OA) is the third most common diagnosis made by general practitioners in older patients. The aim of this study was to compare the function scores of different surgeries in the treatment of knee osteoarthritis (KOA). METHODS: Cohort studies about different surgical treatments for KOA were included with a comprehensive search in PubMed, Cochrane Library, and Embase. The standard mean difference (SMD) value was evaluated and the surface under the cumulative ranking (SUCRA) curve was drawn with a combination of direct and indirect evidence. A total of 265 eligible patients were enrolled and served as the nonoperative treatment group, osteotomy group, unicompartmental knee arthroplasty (UKA) group, total knee arthroplasty (TKA) group, and arthroscopic surgery group. Before surgery, 6 months after surgery, 1 year after surgery and 5 years after surgery, the hospital for special surgery (HSS) knee score, Lysholm score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and American knee society score (KSS) were recorded. RESULTS: A total of 9 cohort studies including 954 patients with KOA were finally enrolled into the study. The network-meta analysis revealed that osteotomy and UKA treatments showed a better efficacy on improving the function score. Our cohort study further confirmed that, a higher HSS knee score after 1 year and higher Lysholm score after 6 months and 1 year were observed in the osteotomy and UKA groups, while better HSS knee score and KSS after 6 months and 1 year were showed in the osteotomy and TKA groups. In the TKA group, Lysholm score and KSS were higher and WOMAC score was lower after 5 years than other groups. WOMAC score was lowest in the UKA group after 6 months, 1 year and 5 years of surgery. CONCLUSION: These results provide evidence that function scores of patients with KOA were improved by osteotomy, UKA, TKA, and arthroscopic surgery. And osteotomy and UKA showed better short-term efficacy, while TKA appeared better long-term efficacy. PMID- 29794772 TI - A case report of apical aneurysms and myocardial perfusion deficit with myocardial necrosis due to hypertrophic cardiomyopathy. AB - RATIONALE: Hypertrophic cardiomyopathy (HCM) is a disease that is characterized by inappropriate left ventricular and/or right ventricular hypertrophy and hypercontractility that is often asymmetrical and associated with microscopic evidence of myocardial fiber disarray. The aim of this study was to present a previously under-recognized subset of HCM patients with left ventricular (LV) apical aneurysms. PATIENTS CONCERNS: A 33-year-old man who presented with chest discomfort for 10 days. He had an emerging apical aneurysm in the LV without midventricular obstruction. He had been diagnosed with apical HCM via abnormal electrocardiograms (ECG) and single-photon emission computed tomography (SPECT) for 10 years. This time, a new significant change in ECG and SPECT was identified. Late gadolinium enhancement (LGE) was observed by cardiac magnetic resonance imaging (MRI), and SPECT showed myocardial fibrosis or necrosis involving the apical aneurysm and proximal portion of the heart, which was confirmed by left ventriculography. DIAGNOSES: We present a relatively rare case of HCM patients with apical aneurysms, accompaning by myocardial necrosis markers increased due to ventricular muscle stress increases, rather than obstructive coronary artery disease. INTERVENTIONS: The patient was prescribed aspirin, metoprolol tartrate, perindopril, and atorvastatin and was strongly advised to quit cigarettes and reduce weight. OUTCOMES: Follow-up at half a year turned out well. LESSONS: LGE with a notable progression by ECG and SPECT along with an increase in myocardial necrosis markers in HCM patients with apical aneurysms, as was noted in the present case, is a relatively rare occurrence. Our present case may provide unique insights into the adverse remodelling process and the formation of apical aneurysms in HCM patients. PMID- 29794773 TI - Low preoperative fibrinogen level is risk factor for neurological complications in acute aortic dissection. AB - Aortic arch surgery in patients with acute aortic dissection is frequently complicated by neurological complications and coagulopathy. However, the relationship between the coagulation system and neurological complications in patients with acute aortic dissection has not been clarified. Thus, the aim of this study was to investigate the relationship between the coagulation system and neurological complications in patients with acute aortic dissection.From September 2014 to January 2016, a total of 126 patients with acute type A aortic dissection were enrolled. Perioperative characteristics and standard laboratory tests upon admission were analyzed using univariate and multivariate logistic regression analysis in this study. The primary outcome was the correlation between the coagulation system and neurological complications.Univariate logistic regression analysis showed that the neurological complications (+) group underwent more serious and complicated postoperative outcomes. Multivariable logistic regression analysis revealed serum creatinine level (OR, 1.049; 95% CI, 1.011-1.089; P = .01), white blood cell counts (OR, 1.581; 95% CI, 1.216-2.057; P = .001) and fibrinogen concentration upon admission (OR, 0.189; 95% CI, 0.060 0.596; P = .004) as predictors of neurological complications. However, we found that there was no association between the coagulation system and in-hospital mortality.Low preoperative fibrinogen level is the preferred marker for predicting clinical neurological complications in patients with acute type A aortic dissection treated with surgical repair. PMID- 29794774 TI - Transarterial chemoembolization for unresectable hepatocellular carcinoma: A comparison of the efficacy and safety of 2 embolic agents. AB - The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (P = .029 and .001, respectively), specifically when the tumor size was >5 cm (P = .001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, P = .011). The response differences in higher stages were significant between the 2 groups (P = .035 and .007, respectively). The grades of adverse events were also significantly different between the groups (P = .000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol. PMID- 29794775 TI - Predicting epidermal growth factor receptor gene amplification status in glioblastoma multiforme by quantitative enhancement and necrosis features deriving from conventional magnetic resonance imaging. AB - To study whether some of the quantitative enhancement and necrosis features in preoperative conventional MRI (cMRI) had a predictive value for epidermal growth factor receptor (EGFR) gene amplification status in glioblastoma multiforme (GBM).Fifty-five patients with pathologically determined GBMs who underwent cMRI were retrospectively reviewed. The following cMRI features were quantitatively measured and recorded: long and short diameters of the enhanced portion (LDE and SDE), maximum and minimum thickness of the enhanced portion (MaxTE and MinTE), and long and short diameters of the necrotic portion (LDN and SDN). Univariate analysis of each feature and a decision tree model fed with all the features were performed. Area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the performance of features, and predictive accuracy was used to assess the performance of the model.For single feature, MinTE showed the best performance in differentiating EGFR gene amplification negative (wild-type) (nEGFR) GBM from EGFR gene amplification positive (pEGFR) GBM, and it got an AUC of 0.68 with a cut-off value of 2.6 mm. The decision tree model included 2 features MinTE and SDN, and got an accuracy of 0.83 in validation dataset.Our results suggest that quantitative measurement of the features MinTE and SDN in preoperative cMRI had a high accuracy for predicting EGFR gene amplification status in GBM. PMID- 29794776 TI - Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis. AB - BACKGROUND: Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis, crucial for normal functioning of the kidneys, bones, heart, and nervous system. Different pathologic conditions can affect serum PTH level resulting in hyperparathyroidism or hypoparathyroidism. Our study assessed the association of previously reported polymorphisms with the level of PTH (expressed in pg/mL) among individuals with different pathologic conditions affecting PTH level. METHODS: We searched Web of Science, MEDLINE, and Scopus to identify relevant articles published up to July 2017. The search yielded 6967 publications of which 44 fulfilled the inclusion criteria. We conducted meta-analyses for calcium-sensing receptor gene (CaSR) rs1801725 polymorphism in patients with primary hyperparathyroidism and vitamin D receptor gene (VDR) rs1544410 polymorphism in patients with end-stage renal disease (ESRD). RESULTS: None of the polymorphisms were significantly associated with PTH levels in the overall population. In subgroup analysis by ethnicity for VDR rs1544410 gene polymorphism, we found significant differences under dominant model (SMD: -0.18 [ 0.32, -0.05], P < .01) and AA versus GG comparison (SMD: -0.29 [-0.52, -0.06], P < .01) in Asian patients with ESRD, while nominally significant results (P < .05) were observed for AG versus GG and AA versus GG comparisons in European individuals with ESRD. CONCLUSION: Scientific evidence of genetic association of serum PTH level among individuals with different pathologic conditions remains deficient and published results provide weak evidence. Further well-conducted studies on larger sample sets designed according to evidence-based principles are warranted to assure clinically applicable findings. PMID- 29794777 TI - A novel mutation in the ABCD1 gene of a Chinese patient with X-linked adrenoleukodystrophy: Case report. AB - RATIONALE: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, which is inherited as an X-linked recessive trait. ATP binding cassette subfamily D member 1 (ABCD1) localized to Xq28 is the only gene associated with ALD. PATIENT CONCERNS: We report a case of Chinese boy with childhood cerebral ALD, who began experiencing symptoms at the age of 5 years and 2 months. Very long chain fatty acids analysis revealed high levels of C24/C22 ratio and C26/C22 ratio in the plasma. Magnetic resonance imaging (MRI) showed abnormal bilateral white matter lesions in brainstem, temporal, occipital, and parietal lobes. DIAGNOSES: Direct sequencing of the ABCD1 gene identified a novel c.1502del mutation on exon 6, which causes a substitution of the 501st amino acid from methionine to serine and finally the 557th codon is changed to stop codon. INTERVENTIONS: Special education and rehabilitation therapy. OUTCOMES: The disease progressed rapidly and resulted in death at the age of 8 years. LESSONS: Early detection of mutations in the ABCD1 gene may facilitate diagnosis, genetic counseling and potentially aid prenatal diagnosis of the disease. PMID- 29794778 TI - Preoperative ANemiA among the elderly undergoing major abdominal surgery (PANAMA) study: Protocol for a single-center observational cohort study of preoperative anemia management and the impact on healthcare outcomes. AB - INTRODUCTION: Preoperative anemia and old age are independent risk factors for perioperative morbidity and mortality. However, despite the high prevalence of anemia in elderly surgical patients, there is limited understanding of the impact of anemia on postoperative complications and postdischarge quality of life in the elderly. This study aims to investigate how anemia impacts elderly patients undergoing major abdominal surgery in terms of perioperative morbidity, mortality and quality of life for 6 months postoperatively. METHODS AND ANALYSIS: We will conduct a prospective observational study over 12 months of 382 consecutive patients above 65 years old, who are undergoing elective major abdominal surgery in Singapore General Hospital (SGH), a tertiary public hospital. Baseline clinical assessment including full blood count and iron studies will be done within 1 month before surgery. Our primary outcome is presence of morbidity at fifth postoperative day (POD) as defined by the postoperative morbidity survey (POMS). Secondary outcomes will include 30-day trend of POMS complications, morbidity defined by Clavien Dindo Classification system (CDC) and Comprehensive Complication Index (CCI), 6-month mortality, blood transfusion requirements, days alive out of hospital (DaOH), length of index hospital stay, 6-month readmission rates and Health Related Quality of Life (HRQoL). HRQoL will be assessed using EuroQol five-dimensional instrument (EQ-5D) scores at preoperative consult and at 1, 3, and 6 months. ETHICS AND DISSEMINATION: The SingHealth Centralised Institutional Review Board (CIRB Ref: 2017/2640) approved this study and consent will be obtained from all participants. This study is funded by the National Medical Research Council, Singapore (HNIG16Dec003) and the findings will be published in peer-reviewed journals and presented at academic conferences. Deidentified data will be made available from Dryad Repository upon publication of the results. PMID- 29794779 TI - Efficacy and safety of oral zinc sulfate in the prevention of chemotherapy induced oral mucositis: Protocol for a meta-analysis of randomized controlled trials. AB - BACKGROUND: Oral mucositis has been an extremely serious complication resulted from cytotoxic effects of the chemotherapy among cancer patients. Several randomized controlled trials investigated the efficacy of zinc sulfate in prevention of this morbid condition among cancer patients undergoing chemotherapy, however conclusive findings has not yet been generated. This systematic review will assess the efficacy and safety of oral zinc sulfate for chemotherapy-induced oral mucositis. METHODS: We will electronically search all potential citations in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from their inception to April 2018. The randomized controlled trials, which investigated the efficacy of oral zinc sulfate for chemotherapy-induced oral mucositis will be considered. We will assign 2 independent investigators to perform search, screen citations, extract data, and appraise risk of bias. And then, the primary investigator will adopt RevMan 5.3 software to complete all statistical analyses. ETHICS AND DISSEMINATION: The findings from this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. Moreover, we will disseminate all results in any topic-related conference. REGISTRATION NUMBER: This protocol has been registered with a number of CRD42018093605. PMID- 29794780 TI - Sequential development of multifocal recurrent non-Hodgkin's lymphoma of mucosa associated lymphoid tissue and diffuse large B-Cell lymphoma in a single patient: A case report. AB - RATIONALE: Diffuse large B-cell lymphoma (DLBCL) and extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) belong to Non-Hodgkin's lymphoma (NHL). DLBCL rarely involves the orbit. MALT lymphomas, which account for 8.0% of NHLs, rarely involve parotid gland, trachea and bronchus. PATIENT CONCERNS: We present a rare case of a long-surviving patient (>=10 years) with sequential development of multifocal recurrent non-Hodgkin's lymphoma of mucosa associated lymphoid tissue (MALT) and diffuse large B-Cell lymphoma (DLBCL). In August 2007, a 41-year-old man developed MALT lymphoma in the parotid gland and local irradiation was administered. In July 2008, he exhibited systemic multifocal lymphadenopathy and was diagnosed with DLBCL. He received standard combination chemotherapy and autologous hematopoietic stem cell transplantation. He was well until February 2013 when he developed MALT lymphoma of the bronchus. Subsequently, he received standard combination chemotherapy. In November 2013, the patient had a relapse of the MALT lymphoma by tracheal biopsy and received local radiation. He was well until March 2015 when he developed a MALT lymphoma of the left thigh. He underwent surgery, local irradiation and rituximab monotherapy. In September 2015, surgical resection of the left orbital masses was performed, and the biopsy revealed the presence of DLBCL. One month later, lymphadenopathy was palpated in the neck, the lower left region of the umbilicus, and the left calf. Then he received chemotherapy with rituximab and lenalidomide. In March 2016, the patient underwent surgical resection for a right popliteal mass, and the resection biopsy revealed DLBCL. To date, the patient is still alive. DIAGNOSES: The patient was diagnosed as multifocal recurrent MALT and DLBCL. INTERVENTIONS: Repeated positron emission tomography-computed tomography (CT) and biopsy were performed. OUTCOMES: CT and biopsy revealed sequential development of multifocal recurrent NHLs of MALT lymphoma and DLBCL. The correlation between MALT and DLBCL may represent a Richter transformation. Standard treatments, such as combination chemotherapy, autologous hematopoietic stem cell transplantation, and irradiation, may be driving factors for phenotypic changes in neoplastic cells. LESSONS: Physicians should pay particular attention to the long-term development of other types of NHL after achieving complete remission of one type of NHL. PMID- 29794781 TI - Adiponectin is not associated with renal function decline in community-dwelling elderly adults. AB - Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys >=60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (beta = -0.23; P = .71, beta = 0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (beta = -0.50; P = .46, beta = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys >=60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics. PMID- 29794782 TI - Effect of intra-coronary administration of tirofiban through aspiration catheter on patients over 60 years with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. AB - The aim of this study was to compare the efficacy and safety of 2 approaches for intra-coronary administration of tirofiban (aspiration catheter versus guiding catheter) in patients over 60 years of age undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). It has been suggested that the administration of tirofiban by intra-coronary injection could promote drug absorption in the diseased region and enhance the inhibition of platelet aggregation, decreasing bleeding rates, but little is known about the comparative efficiency and safety of using guiding catheter versus aspiration catheter for delivery.Eighty-nine patients over 60 years of age with STEMI undergoing PCI were randomly divided into 2 groups according to the injection route for intracoronary administration of tirofiban [guiding catheter (n = 41) and aspiration catheter (n = 48)]. Baseline features, epicardial and myocardial perfusion, major adverse cardiac and cerebrovascular events (MACCEs), and bleeding rate were compared.No differences in age, gender, and history of hypertension, hypercholesterolemia, diabetes, and so on were observed (P > .05). The patients in the aspiration catheter group generally had a higher incidence of cerebral vascular disease. Compared with those in the guiding catheter group, patients in the aspiration catheter group obtained more favorable myocardial perfusion (P < .05). In-hospital and at 3-month and 6-month follow-ups, the MACCE rate and frequency of bleeding events were similar between the 2 groups (P > .05).Intra-coronary delivery of tirofiban through aspiration catheter led to better myocardial perfusion in STEMI patients over 60 years of age undergoing PCI compared with intra-coronary injection of tirofiban through guiding catheter. The 2 delivery routes were associated with similar rates of MACCEs and bleeding events. PMID- 29794783 TI - Neuropathic pain after sarcoma surgery: Prevalence and predisposing factors. AB - Surgery for sarcoma frequently causes nerve damage as the dissection often violates the internervous plane. Nerve damage may cause neuropathic pain (NP), which can result in persistent pain after surgery. This is the first study to investigate the prevalence and associated factors of postoperative NP in patients who underwent surgery for sarcoma of the extremities or pelvis.Patients (n = 144) who underwent curative surgery at least 6 months prior to the visit for histologically confirmed sarcoma were enrolled. The presence of NP was assessed by administering PainDetect, a widely used questionnaire for detecting NP. Patients with PainDetect scores >=13 were considered to have NP. The possible factors that might be associated with the development of NP were investigated: patient characteristics, tumor characteristics, extent of surgery, and adjuvant therapy.Out of 144 patients, 36 patients (25%) had NP. Patients with NP had significantly worse visual analog scale score (P < .001), Toronto Extremity Salvage Score (P < .001), and Musculoskeletal Tumor Society Rating Scale score (P < .001) than patients without NP. Among the possible factors associated with NP, patients with NP were more likely to have undergone pelvic surgery (P = .002) and multiple surgeries (P = .014) than patients without NP. In logistic regression analysis, pelvic surgery (odds ratio = 5.05, P = .005) and multiple surgeries (odds ratio = 2.33, P = .038) were independent factors associated with NP after sarcoma surgery.This study suggests that the prevalence of NP after surgery for sarcoma is considerable. Surgery of the pelvis and multiple surgeries are predictive of postoperative persistent NP. PMID- 29794784 TI - Cortical thickness contributes to cognitive heterogeneity in patients with type 2 diabetes mellitus. AB - The aim of this study was to investigate cerebral cortical thickness alterations in patients with type 2 diabetes mellitus (T2DM) and their association with mild cognitive impairment (MCI).Thirty T2DM patients without MCI, 30 T2DM patients with MCI, and 30 healthy controls were recruited. All subjects underwent high resolution sagittal T1-weighted structural imaging using a 3-dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. The cortical thicknesses of the whole brain of the 3 groups were analyzed and compared using analysis of variance (ANOVA) test. Partial correlations between the cortical thicknesses of each brain region and standard laboratory testing data were analyzed for the T2DM without MCI group. The associations between cortical thicknesses and neuropsychological scale scores were also analyzed in the T2DM with MCI group.Compared with the healthy controls, the T2DM without MCI group showed statistically significant reduction in the cortical thickness of the left posterior cingulate gyrus, right isthmus cingulate gyrus, middle temporal gyrus, paracentral lobule, and transverse temporal gyrus. No significant correlation was found between the standard laboratory testing data and the cortical thicknesses of these cerebral regions. Compared with the T2DM without MCI group, the cortical thickness alterations in the T2DM with MCI group were bidirectional. Increased cortical thickness was found in the left parahippocampal gyrus and the right isthmus cingulate gyrus. Decreased cortical thickness was observed in the left pars triangularis and the right pars opercularis. Significant correlations were found between the cortical thickness of the right pars opercularis and the Complex Figure Test-delayed recall scores (r = 0.464, rho = 0.015), Trail Making Test A consuming time (r = -0.454, rho = 0.017), and Montreal Cognitive Assessment scores (r = 0.51, rho = 0.007).T2DM could influence the gray matter of several brain regions. The cortical thickness reduction of the right pars opercularis may be a biomarker of cognitive impairment and play an important role in its pathophysiological mechanism. PMID- 29794785 TI - Association of various glycemic variability indices and vascular outcomes in type 2 diabetes patients: A retrospective study. AB - Both blood glucose (BG) level and glycemic variability (GV) significantly associate with diabetes-related complications. However, the criterion standard in GV assessment is absent. We aimed to compare different GV indices in association of vascular outcomes.Ten commonly used GV indices based on self-monitored BG data were calculated, and their associations of vascular outcomes including coronary artery disease (CAD), stroke, and chronic kidney disease (CKD) were compared.In total, 288 type 2 diabetes patients (66.5 +/- 11.1 years old) were included in present analysis. Spearman correlation analysis showed that only mean amplitude of glycemic excursions (MAGE) significantly correlated with both estimated glomerular filtration rate and urinary albumin creatinine ratio (P <= .03). In Cochran-Armitage trend test, vascular outcomes were significantly associated with the increment of BG risk index and MAGE (P <= .03). After adjustment for potential confounders, multiple logistic regression results suggested that BG risk index and MAGE still significantly associated with these three vascular outcomes (P <= .01), whereas the other GV indices did not. Receiver operating characteristic curve analysis showed that the abilities of BG risk index and MAGE were similar in identifying CAD, stroke, or CKD.BG risk index and MAGE were better associated with vascular outcomes than other GV indices in type 2 diabetes patients. PMID- 29794786 TI - Identification of differentially expressed genes in childhood asthma. AB - Asthma has been the most common chronic disease in children that places a major burden for affected people and their families.An integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) in childhood asthma compared with normal control. We also obtained the differentially methylated genes (DMGs) in childhood asthma according to GEO. The genes that were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction network construction were performed to interpret biological functions of DEGs. We performed q-RT-PCR to verify the expression of selected DEGs.One DNA methylation and 3 gene expression datasets were obtained. Four hundred forty-one DEGs and 1209 DMGs in childhood asthma were identified. Among which, 16 genes were both differentially expressed and differentially methylated in childhood asthma. Natural killer cell mediated cytotoxicity pathway, Jak-STAT signaling pathway, and Wnt signaling pathway were 3 significantly enriched pathways in childhood asthma according to our KEGG enrichment analysis. The PPI network of top 20 up- and downregulated DEGs consisted of 822 nodes and 904 edges and 2 hub proteins (UBQLN4 and MID2) were identified. The expression of 8 DEGs (GZMB, FGFBP2, CLC, TBX21, ALOX15, IL12RB2, UBQLN4) was verified by qRT-PCR and only the expression of GZMB and FGFBP2 was inconsistent with our integrated analysis.Our finding was helpful to elucidate the underlying mechanism of childhood asthma and develop new potential diagnostic biomarker and provide clues for drug design. PMID- 29794787 TI - The evaluation of acute physiology and chronic health evaluation II score, poisoning severity score, sequential organ failure assessment score combine with lactate to assess the prognosis of the patients with acute organophosphate pesticide poisoning. AB - The aim of this study was to assess the ability of acute physiology and chronic health evaluation II (APACHE II) score, poisoning severity score (PSS) as well as sequential organ failure assessment (SOFA) score combining with lactate (Lac) to predict mortality in the Emergency Department (ED) patients who were poisoned with organophosphate.A retrospective review of 59 stands-compliant patients was carried out. Receiver operating characteristic (ROC) curves were constructed based on the APACHE II score, PSS, SOFA score with or without Lac, respectively, and the areas under the ROC curve (AUCs) were determined to assess predictive value. According to SOFA-Lac (a combination of SOFA and Lac) classification standard, acute organophosphate pesticide poisoning (AOPP) patients were divided into low-risk and high-risk groups. Then mortality rates were compared between risk levels.Between survivors and non-survivors, there were significant differences in the APACHE II score, PSS, SOFA score, and Lac (all P < .05). The AUCs of the APACHE II score, PSS, and SOFA score were 0.876, 0.811, and 0.837, respectively. However, after combining with Lac, the AUCs were 0.922, 0.878, and 0.956, respectively. According to SOFA-Lac, the mortality of high-risk group was significantly higher than low-risk group (P < .05) and the patients of the non survival group were all at high risk.These data suggest the APACHE II score, PSS, SOFA score can all predict the prognosis of AOPP patients. For its simplicity and objectivity, the SOFA score is a superior predictor. Lac significantly improved the predictive abilities of the 3 scoring systems, especially for the SOFA score. The SOFA-Lac system effectively distinguished the high-risk group from the low risk group. Therefore, the SOFA-Lac system is significantly better at predicting mortality in AOPP patients. PMID- 29794788 TI - Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection: A systematic review and meta analysis of randomized clinical trials. AB - BACKGROUND: We sought to conduct a systemic review and meta-analysis of randomized clinical trials to assess the efficacy and safety of photodynamic therapy (PDT) in cervical intraepithelial neoplasia (CIN) and cervical human papilloma virus (HPV) infection. METHODS: The Medline, EMBASE, and Cochrane Central Register databases were searched using relevant keywords for entries up to May 1, 2017, irrespective of year of publication. The language was restricted to English. Randomized clinical trials and qualitative studies comparing PDT and placebo for CIN or HPV-positive patients were included. We assessed the evidence quality using a risk of bias graph in RevMan V5.3 and the Grading of Recommendations Assessment, Development, and Evaluation scoring system. RESULTS: Of the 168 studies identified, only 4 RCTs met the inclusion criteria for meta analysis. In all, 292 and 141 patients received PDT or placebo, respectively. PDT significantly increased the complete remission rate (CRR) among those with CIN (odds ratio [OR]: 2.51 [1.23-5.12]; P = .01) and HPV infection (OR: 3.82 [1.91 7.65]; P = .0002). The adverse events rate (AER) for PDT was greater than that for placebo (OR: 13.32 [4.44, 40.02]; P < .00001). The overall evidence quality was very low. Similarly, in a systematic review including 21 qualitative records, the CRRs for CIN patients with PDT and cervical HPV infection patients with PDT were 82.0% and 77.5%, respectively. The AER for PDT was 31.6%, which was lower than that observed in our meta-analysis (74.6%). CONCLUSIONS: PDT that targets CIN or cervical HPV infection improves the CRR, but slightly compromises safety. Further studies are necessary to identify the most effective and least toxic photosensitizer. PMID- 29794789 TI - The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study. AB - To investigate the impact of comorbid diseases on rheumatoid arthritis (RA) outcome.All patients diagnosed with RA since 2006, who were registered in our local Danbio registry, were included in this cohort study. Patients' demographics, serology results, and Disease Activity Score in 28 joints-C reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months of treatment initiation were collected. Patients' electronic hospital records were evaluated for a positive history of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency, and the presence of other diagnosed autoimmune diseases.1035 RA patients were included. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid diseases and female gender (P < .001); DM and greater age (P < .001); primary hyperparathyroidism and longer disease duration (P = .002); other diagnosed autoimmune diseases and antinuclear antibody positivity (P < .001). RA patients with thyroid diseases (P = .001) and other comorbid autoimmune diseases (P < .001) had significantly poorer initial response to the RA treatment compared to patients with isolated RA.Univariate analyses revealed that age, the presence of thyroid diseases, the presence of other diagnosed autoimmune diseases and DAS28-CRP at the time of diagnosis were significantly associated with DeltaDAS28-CRP. Additionally, multivariate analysis demonstrated that DeltaDAS28-CRP deterioration was significantly correlated to the presence of thyroid diseases (unstandardized regression coefficient (standard error); -0.188 (0.088), P = .030) and the presence of other diagnosed autoimmune diseases (-0.537 (0.208), P = .010).RA patients are at increased risk of specific comorbidities with possible impact on the treatment outcome. To improve this situation, periodic assessment of comorbidities should be considered. PMID- 29794790 TI - Left lung hypoplasia with a right tuberculous pleural effusion after childbirth: A case report. AB - RATIONALE: Unilateral hypoplasia of the lung is a rare congenital condition, the mechanism of which is poorly understood. Primary pulmonary hypoplasia occurring in an adult is extremely rare and we present what is probably the first case of a link to a tuberculous pleural effusion in a young woman after childbirth. PATIENT CONCERNS: Herein, we describe a 31-year-old woman with left lung hypoplasia, and she not only survived to adulthood without problems, but was able to deliver a baby in natural labor. DIAGNOSES: Left lung hypoplasia, right tuberculous pleural effusion. INTERVENTIONS: We initiated an anti-tuberculosis treatment for this patient with dose adjustments to her weight of isoniazid (0.3 g/day), rifampicin (0.45 g/day), pyrazinamide (1.5 g/day), and ethambutol (0.75 g/day) for 2 months then isoniazid and rifampicin for another 4 months. OUTCOMES: Ten days later after beginning therapy, she became afebrile and the pleural effusion resolved. No recurrence was observed during a 6-month follow-up period. LESSONS: In clinical practice, if one sees a chest x-ray revealing complete or incomplete opacification of a hemithorax with volume loss and history of repeated respiratory infections, one should consider the possibility of unilateral pulmonary hypoplasia. In such cases, regular close follow-up is important to minimize infections and to prevent development of cor pulmonale or respiratory failure. PMID- 29794791 TI - Oncogenomic analysis identifies novel biomarkers for tumor stage mycosis fungoides. AB - Patients with mycosis fungoides (MF) developing tumors or extracutaneous lesions usually have a poor prognosis with no cure has so far been available. To identify potential novel biomarkers for MF at the tumor stage, a genomic mapping of 41 cutaneous lymphoma biopsies was used to explore for significant genes.The gene expression profiling datasets of MF were obtained from Gene Expression Omnibus database (GEO). Gene modules were simulated using Weighted Gene Co-expression Network Analysis (WGCNA) and the top soft-connected genes (hub genes) were filtrated with a threshold (0.5). Subsequently, module eigengenes were calculated and significant biological pathways were enriched based on the KEGG database.Four genetic modules were simulated with 3263 genes collected from the whole genomic profile based on cutoff values. Significant diseases genetic terminologies associated with tumor stage MF were found in black module. Subsequently, 13 hub genes including CFLAR, GCNT2, IFNG, IL17A, IL22, MIP, PLCG1, PTH, PTPN6, REG1A, SNAP25, SUPT7L, and TP63 were shown to be related to cutaneous T-cell lymphoma (CTCL) and adult T-cell lymphoma/leukemia (ATLL).In summary, in addition to the reported genes (IL17F, PLCG1, IFNG, and PTH) in CTCL/ATLL, the other high instable genes may serve as novel biomarkers for the regulation of the biological processes and molecular mechanisms of CTLT (MF/SS). PMID- 29794792 TI - Simultaneous involvement of 11q23 translocation resulting in chimeric MLL-AFF1 and a second translocation [t (9;21) (p13; p11.2)] in an infant acute lymphoblastic leukemia patient at relapse: A case report. AB - RATIONALE: Three-way translocations occasionally occur in MLL-AFF1 fusion and other fusion gene. However, the complex chromosomal rearrangements in the study were the first report. PATIENT CONCERNS: We present novel cryptic and complex chromosomal rearrangements [der (21) t (9; 21) (p13; p11.2)] in an infant patient with relapsed acute lymphoblastic leukemia (ALL). DIAGNOSES: The diagnosis was based on morphologic, cytochemical, and immunophenotypic criteria proposed by the French-American-British Committee, and karyotype, fluorescence in situ hybridization, array comparative genomic hybridization. INTERVENTIONS: The patient was given chemotherapy with standard protocol for ALL. OUTCOMES: The patient had unfavorable prognostic outcome based on the cytogenetic and molecular cytogenetic markers. After short remission, the patient relapsed. LESSONS: MLL AFF1, resulting from t(4;11)(q21;q23), is regarded as the hallmark of infant t(4;11) pre-B/mixed B-ALL. It is associated with a dismal prognosis and the multiple-way translocation involving chromosomes 4, 11 and 11 may function as an enhancer. PMID- 29794793 TI - Effect of acupuncture and its influence on visceral hypersensitivity in IBS-D patients: Study protocol for a randomized controlled trial. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. METHOD: This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. DISCUSSION: The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. TRIAL REGISTRATION: This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445). PMID- 29794795 TI - Expression profile of circular RNAs in infantile hemangioma detected by RNA-Seq. AB - BACKGROUND: Circular RNAs (circRNAs) have emerged as a novel class of widespread non-coding RNAs, and they play crucial roles in various biological processes. However, the characterization and function of circRNAs in infantile hemangioma (IH) remain elusive. METHODS: In this study, we used RNA-Seq and circRNA prediction to study and characterize the circRNAs in IH tissue and a matched normal skin control. Specific circRNAs were verified using real-time polymerase chain reaction. RESULTS AND CONCLUSION: We found that of the 9811 identified circRNAs, 249 candidates were differentially expressed, including 124 upregulated and 125 downregulated circRNAs in the IH group compared with the matched normal skin control group. A set of differentially expressed circRNAs (in particular, hsa_circRNA001885 and hsa_circRNA006612 expression) were confirmed using qRT-PCR. Gene ontology and pathway analysis revealed that compared to matched normal skin tissues, many processes that were over-represented in IH group were related to the binding, protein binding, gap junction, and focal adhesion. Specific circRNAs were associated with several micro-RNAs (miRNAs) predicted using miRanda. Altogether, our findings highlight the potential importance of circRNAs in the biology of IH and its response to treatment. PMID- 29794794 TI - Clear cell carcinoma of the ovary: Clinicopathologic features and outcomes in a Chinese cohort. AB - This retrospective analysis aimed to clarify the clinical and pathologic features of ovarian clear cell carcinoma (OCCC), and to determine the factors predictive of survival.Data waereextracted from OCCC patients who underwent primary surgery followed by adjuvant chemotherapy in Obstetrics & Gynecology Hospital of Fudan University between January2007 and December 2014. Kaplan-Meier survival estimates and Cox proportional hazards model were used for survival analyses.Of 130 patients (mean age = 56.2 years), 66.2% had stage I disease when the 5-year overall survival and 5-year disease-free survival were 89.2% and 88.1%, respectively. Patients frequently presented with large pelvic mass (>10 cm) and mild-to-moderate elevation of serological CA125 (<=200U/ mL). 60.7% of the cases at stage III/IV exhibited resistance to platinum-based chemotherapy; 37.69% of the tumors arose from endometriosis. On multivariate analysis, stage and chemoresistance were independent prognostic factors predictive for poorer survival. Survival at stage IC1 (surgical rupture) was comparable to that at stage IA (capsule intact), whereas survival at stage IC2/IC3 (rupture before surgery) was significantly worse than that at stage IA.OCCC shows distinct features compared to other epithelial ovarian cancers. FIGO stage and response to chemotherapy affect prognosis independently. Arising from endometriosis is not associated with better survival. Preoperative rupture rather than intraoperative rupture confers an adverse prognosis in otherwise stage IA disease. PMID- 29794797 TI - Evaluation of the physical activity level, nutrition quality, and depression in patients with metabolic syndrome: Comparative study: Erratum. PMID- 29794796 TI - High preoperative serum leptin level is an independent risk factor for deep vein thrombosis after total knee arthroplasty in osteoarthritis patients: A prospective and cross-sectional study. AB - It suggests that a high leptin level may increase the risk of venous thromboembolism (VTE) in animal studies. However, clinical studies in this field are still largely unexplored. Our objective was to evaluate the relationship between the preoperative serum leptin levels and postoperative VTE incidence in osteoarthritis (OA) patients who underwent total knee arthroplasty (TKA) at our institute.We conducted a prospective and cross-sectional study in these OA patients from March 2014 to March 2016. Preoperative leptin levels were analyzed by Luminex assays. VTE was assessed preoperatively and on postoperative day 5 and 7. The potential risk factors for VTE were also documented.We enrolled 203 OA patients. No PE was detected and DVT was diagnosed in 34 patients postoperatively. There were significant differences between the median leptin levels in DVT group and non-DVT group [25.13 ng/mL (interquartile range, 14.51 44.31) vs 18.71 ng/mL (8.26-28.99), P = .007]. The relative risk of DVT significantly increased with natural logarithm (ln) leptin (per SD increase) (OR 2.37, 95% confidence interval (95% CI), 1.29-4.33, P = .005). Multivariate analyses adjusted for potential confounders showed ln leptin (per SD increase) was significantly associated with the relative risk of DVT (OR 2.17, 95% CI, 1.01 4.64, P = .046). When patients were subdivided into tertiles according to their leptin values, the OR for DVT increased with increasing tertiles of serum leptin (OR 1.03, 95% CI, 1.01-1.06, P for trend = .023).In the present study, our results indicate that a high preoperative leptin level may be an independent risk factor for postoperative DVT. PMID- 29794800 TI - Real role of beta-blockers in regression of left ventricular mass in hypertension patients: Bayesian network meta-analysis: Erratum. PMID- 29794799 TI - Malignant external otitis following radiotherapy for oral cancer: A case report. AB - RATIONALE: Although an ototoxicity is well-known as adverse event of the radiotherapy, it is not widely known that immunosuppressed patients who underwent radiotherapy in head and neck region have risk of malignant external otitis. PATIENT CONCERNS: A 68-year-old man with diabetes, who had been diagnosed as intraosseous squamous cell carcinoma of the right mandible, underwent surgical resection. He received a total of 60 Gy/30Fr postoperative radiation. Four months after the course of radiation, he suffered from right aural fullness, otalgia and otorrhea. DIAGNOSES: Clinical examination revealed granulation and existence of Pseudomonas aeruginosa in the external auditory canal. Computed tomography showed expansive inflammation and erosion in the temporal bone. The patient is elderly and diabetes. These findings led to the diagnosis of malignant external otitis. INTERVENTIONS: The ear irrigation and administration of quinolones were started. Afterwards, fistula was formed in the oral cavity, and connected to the right external auditory canal. Therefore, irrigations were performed not only from ear but also from the oral fistula. OUTCOMES: Eight weeks after starting treatment, the malignant external otitis was completely healed. LESSONS: Physicians should raise awareness of malignant external otitis in immunosuppressed patients with oral cancer after radiotherapy. PMID- 29794801 TI - Combined Superficial and Deep Serratus Plane Block With Bupivacaine, Dexamethasone, and Clonidine in the Treatment of a Patient With Postmastectomy Pain Syndrome: A Case Report. AB - Postmastectomy pain syndrome poses a significant treatment challenge. We present the case of a 42-year-old woman who presented to our pain clinic with a 16-month history of postmastectomy pain. We performed a combined superficial and deep serratus plane block using bupivacaine, dexamethasone, and clonidine. At 1-month follow-up, the patient had 100% pain relief. At 2-month follow-up, her pain was 5/10. The block was repeated with the same drugs at 3 months with similar pain relief. This case illustrates the utility of a combined superficial and deep serratus plane block in postmastectomy pain syndrome with a possible benefit from added dexamethasone and clonidine. PMID- 29794798 TI - Colonic metastasis from breast carcinoma detection by CESM and PET/CT: A case report. AB - INTRODUCTION: Metastatic spread in invasive lobular carcinoma (ILC) of breast mainly occurs in bones, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract. Metastases to the GI tract may arise many years after initial diagnosis and can affect the tract from the tongue to the anus, stomach being the most commonly involved site. Clinical presentations are predominantly nonspecific, and rarely asymptomatic. CEA, CA 15-3, and CA 19-9 may be informative for symptomatic patients who have had a previous history of breast cancer. CASE PRESENTATION: We introduce the case of asymptomatic colonic metastasis from breast carcinoma in a 67-year-old woman followed-up for Luminal A ILC. Diagnosis was performed through positron emission tomography/computed tomography (PET/CT) scan and contrast-enhancement spectral mammography (CESM), steering endoscopist to spot the involved intestinal tract and in ruling out further dissemination in the breast parenchyma. CONCLUSION: In colonic metastases, tumor markers might not be totally reliable. In asymptomatic cases, clinical conditions might be underappreciated, missing local or distant recurrence. CT and PET/CT scan might be useful in diagnosing small volume diseases, and steering endoscopist toward GI metastasis originating from the breast. CESM represents a tolerable and feasible tool that rules out multicentricity and multifocality of breast localization. Moreover, particular patients could tolerate it better than magnetic resonance imaging (MRI). PMID- 29794802 TI - Continuous Erector Spinae Plane Catheter for Analgesia After Infant Thoracotomy: A Case Report. AB - The erector spinae plane block is an emerging technique for the provision of thoracolumbar analgesia with reported pediatric applications. We describe the placement of a continuous erector spinae plane catheter at the T5-T6 level in a 7 month-old infant who was undergoing thoracotomy for left upper lobectomy due to congenital pulmonary airway malformation. This technique resulted in outstanding analgesia without the need for opioid rescue analgesia. This block has a low degree of technical difficulty and is placed in area devoid of nearby critical structures and could be used in a number of potentially painful interventions. PMID- 29794803 TI - Anesthetic Action and "Quantum Consciousness": A Match Made in Olive Oil. PMID- 29794804 TI - A New Reference Source for Postmortem Body Measurements and Organ Weights in Neonates and Infants: A Statistical Analysis Based on Sudden Death Classification (Part 2). AB - Reference charts for body and organ measurements of neonates and infants were derived from data on 900 investigations done by the Office of the Chief Coroner for Ontario. The statistical analyses in this new reference source addressed deficiencies in sources currently available to pathologists.The present study also considered whether organ weights differed based on the classification of infant deaths using the original definition of either sudden infant death syndrome (SIDS) or sudden unexplained death (SUDS) which considers cases occurring in an unsafe sleeping environment or under adverse socioeconomic conditions. Cases of SUDS for both sexes peaked in 5 to 16 weeks of age. The thymus in the SUDS/SIDS age groups less than 25 weeks weighed more than the control group. Adrenal weights in SUDS cases between 9 and 16 weeks weighed less than SIDS cases. This could mean that deaths in unsafe sleep environments are truly sudden in infants who may have a limited adrenal response to acute hypoxia but have been unaffected by preceding chronic stressors. PMID- 29794806 TI - The potential role of pharmacogenomics and biotransformation in hypersensitivity reactions to paracetamol. AB - PURPOSE OF REVIEW: The aim of the present review is to discuss recent advances supporting a role of paracetamol metabolism in hypersensitivity reactions to this drug. RECENT FINDINGS: Recent developments in the identification of novel paracetamol metabolites, as well as in allele frequencies and functional effects of genetic variation leading to the bioavailablity of reactive paracetamol metabolites, have led to the identification of potential pharmacogenomic and metabolomic targets in studies seeking mechanisms involved in hypersensitivity reactions caused by this drug. Particularly relevant are identification of araquidonate metabolites, identification of specific-binding sequences for reactive paracetamol metabolite-protein adducts, and studies on the frequencies and the functional impact of duplication or multiduplication of genes involved in the formation of reactive metabolites, as well as complete gene deletion or deleterious mutations in genes involved in the detoxification of paracetamol reactive metabolites. In addition, recent evidence points to sex, ethnic origin and age as relevant factors in the production of reactive paracetamol metabolites. SUMMARY: High inter-individual variability in the production of reactive paracetamol metabolites exists, and factors leading to increased bioavailability of reactive paracetamol metabolites are being uncovered. Additional research is required to link these factors to paracetamol-induced hypersensitivity reactions. PMID- 29794805 TI - Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition. AB - Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition. PMID- 29794807 TI - Left Main Disease: What Is the Correct Approach to Revascularization? AB - Percutaneous coronary intervention of the left main coronary artery has evolved through registries and meta analyses, supported by results from the EXCEL [Everolimus-Eluting Stents (EES) or Bypass Surgery for Left Main Coronary Artery Disease] and NOBLE (Percutaneous Coronary Angioplasty versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trials as an acceptable alternative to coronary artery bypass grafting in patients with low and intermediate Syntax scores. Advances in stenting strategies and the availability of larger diameter drug-eluting stents improve patient safety and optimize procedural and patient outcomes. PMID- 29794809 TI - Photobiomodulation or low-level laser therapy in the management of cancer therapy induced mucositis, dermatitis and lymphedema. AB - PURPOSE OR REVIEW: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT) also known as PhotoBioModulation (PBM) when used for the prevention and/or treatment of oral mucositis in patients undergoing radiotherapy for head and neck cancer, or high-dose chemotherapy regimens. This review aims at giving the state of the art of this technique in this indication. RECENT FINDINGS: Recent advances in LLLT/PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with cancer treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. SUMMARY: The article discusses LLLT/PBM mechanisms of action, dosimetry, and safety, and aims to identify some cancer treatment side effects for which LLLT/PBM may prove to be effective (oral mucositis, radiation dermatitis, lymphedema). In addition, LLLT/PBM parameters for each of these complications are suggested and future research directions are discussed. PMID- 29794808 TI - Acromegalic Cardiomyopathy: An Overview of Risk Factors, Clinical Manifestations, and Therapeutic Options. AB - Acromegaly is a rare endocrine disorder that carries a significant burden of cardiovascular morbidity and mortality. Abnormalities of the growth hormone/insulin-like growth factor-1 axis in acromegaly lead to the characteristic cardiovascular manifestations of this disease. One hallmark feature of the disease is acromegalic cardiomyopathy, a syndrome of progressive cardiac dysfunction characterized by left ventricular hypertrophy, diastolic dysfunction, and combined systolic and diastolic dysfunction in the very advanced stage. In this article, we review the current concepts regarding the pathophysiology of acromegalic cardiomyopathy and discuss the various risk factors for its development. We also explore the question of whether the alterations in cardiac function are reversible with successful biochemical control of growth hormone excess either medically or surgically. PMID- 29794810 TI - Supportive care in cancer: quo vadis. PMID- 29794811 TI - The unbearable lightness of therapeutic algorithms in colorectal liver metastasis. PMID- 29794813 TI - Improving Geriatric Care Processes on Two Medical-Surgical Acute Care Units: A Pilot Study. AB - The Acute Care for Elders (ACE) Unit model improves cognitive and functional outcomes for hospitalized elders but reaches a small proportion of patients. To disseminate ACE Unit principles, we piloted the "Virtual ACE Intervention" that standardizes care processes for cognition and function without daily geriatrician oversight on two non-ACE units. The Virtual ACE Intervention includes staff training on geriatric assessments for cognition and function and on nurse-driven care algorithms. Completion of the geriatric assessments by nursing staff in patients aged 65 years and older and measures of patient mobility and prevalence of an abnormal delirium screening score were compared preintervention and postintervention. Postintervention, the completion of the assessments for current functional status and delirium improved (62.5% vs. 88.5%, p < .001) and (4.2% vs. 96.5%, p < .001). In a subsample analysis, in the postintervention period, more patients were up to the chair in the past day (36.4% vs. 63.5%, p = .04) and the prevalence of an abnormal delirium screening score was lower (13.6% vs. 4.8%, p = .16). The Virtual ACE Intervention is a feasible model for disseminating ACE Unit principles to non-ACE Units and may lead to increased adherence to care processes and improved clinical outcomes. PMID- 29794812 TI - Genetic causes of resistance to vitamin K antagonists in Polish patients: a novel p.Ile123Met mutation in VKORC1 gene. AB - : Mutations in the genes encoding vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) largely contribute to the inter individual variations in vitamin K antagonists (VKAs) dose requirements. Up to 50% of the dosage variability can be explained by genetic polymorphisms in these genes. We sought to identify the mutations responsible for VKA resistance in a series of Polish patients. Of the 607 patients treated with VKA, 35 (6%) individuals with the VKA resistance defined as a daily dose of acenocoumarol more than 8 mg (n = 15, 43%) or warfarin more than 10 mg (n = 20, 57%) were selected for further mutational analysis using Sanger sequencing (VKORC1) or real-time PCR genotyping (CYP2C9). The indications for anticoagulant treatment were venous thromboembolism (n = 28, 80%), atrial fibrillation (n = 6, 17%), or artificial heart valve (n = 1, 3%). Patients taking medication interfering with VKA were ineligible. Almost all of VKA-resistant patients (n = 34, 97%) possessed at least one VKORC1*3 (n = 29, 83%) or VKORC1*4 (n = 15, 43%) haplotypes. In a 70-year-old man atrial fibrillation patient on the daily acenocoumarol dose of 16 mg, a novel p.Ile123Met (c.369C>G) VKORC1 mutation was found. In-silico analysis showed that the p.Ile123Met can functionally underlie the acenocoumarol resistance, presumably by altering VKA binding. To our knowledge this is the first cohort of Polish patients resistant to VKA evaluated for the causal genetic background. We found one new detrimental mutation underlying VKA resistance. Our study highlights a key role of unidentified environmental factors in VKA resistance in daily clinical practice. PMID- 29794814 TI - Comparison of acoustic radiation force impulse elastography and transient elastography for prediction of hepatocellular carcinoma recurrence after radiofrequency ablation. AB - BACKGROUND: To compare the clinical value of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) for hepatocellular carcinoma (HCC) recurrence prediction after radiofrequency ablation (RFA) and to investigate other predictors of HCC recurrence. PATIENTS AND METHODS: Between 2011 and 2016, 130 patients with HCC who underwent ARFI elastography and TE within 6 months before curative RFA were prospectively enrolled. Independent predictors of HCC recurrence were analyzed separately using ARFI elastography and TE. ARFI elastography and TE accuracy to predict HCC recurrence was determined by receiver operating characteristic curve analysis. RESULTS: Of all included patients (91 men; mean age, 63.5 years; range: 43-84 years), 51 (42.5%) experienced HCC recurrence during the follow-up period (median, 21.9 months). In multivariable analysis using ARFI velocity, serum albumin and ARFI velocity [hazard ratios: 2.873; 95% confidence interval (CI): 1.806-4.571; P<0.001] were independent predictors of recurrence, and in multivariable analysis using TE value, serum albumin and TE value (hazard ratios: 1.028; 95% CI: 1.013-1.043; P<0.001) were independent predictors of recurrence. The area under the receiver operating characteristic curve of ARFI elastography (0.821; 95% CI: 0.747-0.895) was not statistically different from that of TE (0.793; 95% CI: 0.712-0.874) for predicting HCC recurrence (P=0.827). The optimal ARFI velocity and TE cutoff values were 1.6 m/s and 14 kPa, respectively. CONCLUSION: ARFI elastography and TE yield comparable predictors of HCC recurrence after RFA. PMID- 29794816 TI - Antiretroviral implants for treatment and prevention of HIV infection. AB - PURPOSE OF REVIEW: Poor adherence to oral antiretroviral formulations remains the major barrier to the success of long-term treatment and prevention strategies. Although a number of approaches have been developed for long-acting parenteral delivery of antiretroviral drugs, subcutaneous implants are a particularly promising technology as they may be able to provide protective drugs concentrations for a year or longer following a single implant. This review addresses the current status of preclinical and clinical development of antiretroviral implants. RECENT FINDINGS: Subcutaneous implants have been widely used for hormonal contraception and the treatment of hormonally driven malignancies for more than 3 decades. These implants are economical to manufacture and deliver, but require special procedures for insertion and removal. They are generally well tolerated and can remain in place for as long as 5 years. A small number of investigational implants are under development for the delivery of antiretroviral drugs. The most advanced of these, containing the investigational antiretroviral MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a potent nucleoside analog reverse transcriptase translocation inhibitor that demonstrates particular promise for subcutaneous implantation, is closest to testing in human subjects. Investigational implants containing tenofovir alafenamide and nevirapine have also been developed and tested in animal models. SUMMARY: Long-acting antiretroviral implants are a promising new technology, but are in very early stages of development. Potential advantages of these systems include more consistent and predictable drug release than intramuscular injections, and the fact that implants can be removed in the case of adverse events or the desire to stop treatment. PMID- 29794817 TI - Doravirine: a review. AB - PURPOSE OF REVIEW: The current review addresses the role of doravirine (DOR), a novel once-daily nonnucleoside reverse transcriptase inhibitor (NNRTI) in first line therapy at a time in which multiple options are available, and issues of antiviral efficacy, safety, simplicity and cost are critical to make informed decisions. RECENT FINDINGS: DOR combination regimens have been tested in two large randomized double-blinded clinical trials in treatment-naive patients, showing noninferiority to ritonavir-boosted darunavir-based and efavirenz (EFV) based regimens. The main features of DOR are reviewed in this report including its antiviral activity, genetic barrier to resistance, safety, once-daily dosing and coformulation in a single tablet with tenofovir disoproxil fumarate and lamivudine. DOR pharmacokinetics and drug-drug interactions are also reviewed as DOR can be given without food restriction and has no interaction with proton pump inhibitors. DOR has shown a superior safety profile than EFV regarding neuropsychiatric and cutaneous adverse events. DOR is currently being investigated in treatment-experienced patients and in those with transmitted NNRTI drug resistance. SUMMARY: DOR is a promising new NNRTI that could become the preferred drug in its class for treatment initiation. DOR has shown excellent antiviral activity in treatment-naive patients, a better safety profile than EFV and a low potential for drug-drug interactions. PMID- 29794815 TI - Increasing SBP variability is associated with an increased risk of developing incident diabetic foot ulcers. AB - OBJECTIVE: SBP variability may be a target for mitigating end-organ damage associated with vascular disease. We evaluated the relationship between increased SBP variability and risk of incident diabetic foot ulceration. METHODS: Using a nested case-control design, we followed patients diagnosed with diabetes and treated within the US Department of Veterans Affairs Healthcare system for development of a diabetic foot ulcer (event) between 2006 and 2010. Each case was randomly matched to up to five controls based on age, sex, race/ethnicity, and calendar time. SBP variability was computed using at least three blood pressure measurements from the year preceding the event. The association between SBP variability and foot ulceration was examined using conditional logistic regression. Potential protective effects of calcium channel blockers, which blunt SBP variability, were also explored. RESULTS: The study sample included 51 111 cases and 129 247 controls. Compared with those in quartile 1 (lowest variability), patients in quartiles 2-4 had higher adjusted odds ratios for diabetic foot ulcer development: 1.11 (95% CI 1.07-1.16), 1.20 (95% CI 1.15 1.25), 1.29 (95% CI 1.24-1.34) (P for trend <0.001). Calcium channel blockers were associated with reduced risks of ulceration for those without peripheral vascular disease (OR = 0.87, 95% CI 0.84-0.90, P < 0.001) or neuropathy (OR = 0.85, 95% CI 0.82-0.89, P < 0.001) in adjusted subgroup analyses. CONCLUSION: This study describes a graded relationship between SBP variability and risk of diabetic foot ulceration, providing a potential new and modifiable target to reduce this common complication. PMID- 29794818 TI - Rilpivirine long-acting for the prevention and treatment of HIV infection. AB - PURPOSE OF REVIEW: Rilpivirine is a non-nucleoside reverse transcriptase inhibitor approved for the treatment of HIV in combination with other antiretrovirals (ARV). The development of the long-acting formulation of rilpivirine (RPV-LA) and its use in clinical settings is the subject of this review. RECENT FINDINGS: In 2017, the results of the phase IIb study LATTE2 have been published. This study demonstrated that the combination of RPV-LA with a second long-acting agent (cabotegravir) administered intramuscularly every 4--8 weeks was similar in virologic suppression rates to standard of care ARV treatment. SUMMARY: RPV-LA is an injectable nanoparticle suspension for intramuscular use. Phase I studies in healthy volunteers demonstrated that RPV LA, administered at doses between 600 and 1200 mg, was well tolerated and effective in maintaining satisfactory drug concentrations in plasma, vaginal secretions and rectal tissue compartments for at least 4 weeks. RPV-LA efficacy was also shown in a phase II clinical trial in HIV infected patients and phase III studies are currently ongoing. Most study participants stated that they would use or continue using injectables, both in HIV treatment and prevention settings. Long-acting injectable ARVs have the potential to improve the convenience of HIV drug regimens. PMID- 29794820 TI - Respiratory Synkinesis Seen in the Biceps Brachii Muscle Resulting From Meningitis 20 Years Ago. PMID- 29794821 TI - In Defense of a Simplified, Practical Colposcopic Terminology. PMID- 29794819 TI - Psychiatric Emergencies in Pregnancy and Postpartum. AB - The perinatal period is a vulnerable time for the acute onset and recurrence of psychiatric illness. Primary care providers are opportunely positioned to intervene for women who present with mood decompensation, excessive anxiety, or psychosis during the perinatal period. Owing to increased screening efforts in obstetrical clinics and amount of contact during the perinatal period, obstetricians may be able to identify patients who need treatment before their symptoms become severe. In this article, we address imminent and emergent psychiatric symptoms in the perinatal period including management and risk reduction to help obstetrician/gynecologists treat and/or refer patients as clinically appropriate. PMID- 29794822 TI - Zidovudine-Based Treatments Inhibit the Glycosylation of ADAM17 and Reduce CD163 Shedding From Monocytes. AB - BACKGROUND: sCD163, a biomarker of monocyte-macrophage activation, has been identified as a predictor of all-cause mortality in treated HIV-infected individuals. Nevertheless, little is known about whether different antiretroviral drugs differentially regulate sCD163 levels and monocyte activation. METHODS: A total of 123 patients receiving zidovudine (ZDV)-based (n = 55) or tenofovir disoproxil fumarate (TDF)-based (n = 68) antiretroviral regimens were enrolled, and their viral loads, CD4 counts, as well as plasma sCD163 and sCD14 levels were quantified. Twenty-eight (14 in each group) patients donated additional blood samples for flow cytometry and gene expression analyses using purified monocytes. THP-1 cultures were also used to investigate the effect of ZDV on ADAM17, which is responsible for CD163 shedding. RESULTS: As compared to the TDF-treated group, the ZDV-treated group had lower plasma sCD163 levels and higher CD163 expression on CD14++CD16 monocytes. Five metabolic-inflammatory genes exhibited significantly different expression levels between purified monocytes of the ZDV and TDF groups (IL-6, 2.90-fold lower in ZDV group, P < 0.001; iNOS, 1.81-fold higher; CX3CR1, 1.72-fold lower; MIP-1beta, 1.10-fold lower; and PPARgamma-1, 1.36-fold higher, P < 0.05). Moreover, we show that ZDV treatment increases the surface expression of CD163 in cultured THP-1 cells, accompanied by the inhibition of glycosylation and surface expression of ADAM17. CONCLUSIONS: Compared with TDF treatment, ZDV treatment causes lower plasma sCD163 levels, probably by inhibiting the glycosylation of ADAM17 and CD163 shedding. Our results show that ZDV functions as an ADAM17 inhibitor in vivo and extend our understanding of its immune-modulatory effects and adverse effects. PMID- 29794823 TI - Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy. AB - BACKGROUND: Obesity alters adipose tissue immunology, and these changes may be reflected in circulating soluble inflammatory biomarker and T-cell subset profiles measured in HIV research studies. METHODS: We recruited 70 adults with HIV (50% obese) on efavirenz, tenofovir, and emtricitabine, virologic suppression for >2 years, and no rheumatologic or other known inflammatory conditions. We measured fasting plasma levels of several markers of innate immunity and major CD4 and CD8 T-cell subsets. We assessed relationships between measurements of total adiposity [body mass index (BMI), dual-energy X-ray absorptiometry quantified fat mass index (FMI), and plasma leptin] and the immunologic parameters using covariate-adjusted Spearman's rank correlations. RESULTS: The cohort was 43% women, 54% nonwhite, and median age was 45 years. Higher BMI, FMI, and plasma leptin were consistently associated with higher C-reactive protein, serum amyloid A, and interleukin-6 (P < 0.01 for all), but lower interleukin-10 (P <= 0.02 for all). BMI and FMI were positively associated with soluble tumor necrosis factor-alpha receptor 1 levels (P <= 0.02 for both), and a positive correlation approached significance for all 3 body composition measurements with soluble CD163 (P <= 0.09 for all). Higher BMI and FMI were associated with lower CD38 expression on CD4 T cells (P <= 0.04 for both), but higher CD69 expression (P <= 0.01 for BMI and FMI, P = 0.07 for leptin). CONCLUSIONS: Greater adiposity is associated with alterations in a limited set of circulating immune markers, potentially reflecting changes known to occur in adipose tissue with treated HIV infection. Measuring total fat mass radiographically did not yield substantively different results compared with BMI. PMID- 29794825 TI - Isolated Conjunctival Inflammation as a Manifestation of IgG4-Related Disease. AB - PURPOSE: To report a unique case of isolated conjunctival inflammation from IgG4 related disease (IgG4-RD) confirmed by pathology. METHODS: A single interventional case of conjunctival IgG4-RD. RESULTS: A 63-year-old woman presented with a chronic, solitary, vascularized, tan-colored, and raised conjunctival lesion measuring 7.5 * 8.0 * 1.2 mm located at the temporal bulbar conjunctiva. An excisional biopsy was diagnostic of IgG4-RD based on the classic fibrosis pattern, 120 IgG4-positive plasma cells per high-power field, and an overwhelming majority of IgG4-positive cells among IgG plasma cells. No orbital or systemic involvement was found on clinical examination, imaging, and laboratory workup. The serum IgG4 level was normal (87.1 mg/dL). The patient was free of recurrence at 6-month follow-up. CONCLUSIONS: Isolated conjunctival inflammation without orbital involvement can be a presentation of IgG4-RD. PMID- 29794824 TI - Limbal Stem Cell Deficiency Secondary to Diffuse Non-necrotizing Anterior Scleritis: A Clinicopathological Report. AB - PURPOSE: To report a case of limbal stem cell deficiency (LSCD) secondary to diffuse non-necrotizing anterior scleritis (DNNAS). METHOD: Interventional case report with clinicopathologic correlation. A 69-year-old white woman with known Crohn disease presented with DNNAS. The acute inflammatory phase was treated with topical and systemic steroids. After DNNAS, she developed secondary LSCD with loss of limbal palisades of Vogt and conjunctivalization of the corneal surface and corneal haze. She underwent superficial keratectomy combined with autologous limbal stem cell grafting from the fellow eye. The keratectomy specimen was sent for pathological examination. RESULTS: There were no intraoperative or post operative complications. Histopathology and immunohistochemistry showed a cytokeratin 19-positive and cytokeratin 3- and cytokeratin 12 negative epithelium in keeping with a conjunctival phenotype on the corneal surface. CONCLUSIONS: LSCD can be a rare complication of DNNAS. After control of ocular surface inflammation, autologous limbal stem cell grafting and amniotic membrane transplantation can be effective in normalizing the ocular surface. PMID- 29794826 TI - Clinical and Histological Characterization of Toxic Keratopathy From Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate: [RETRACTED]. AB - PURPOSE: To report the first histological characterization of microcyst-like epithelial keratopathy (MEK) associated with depatuxizumab mafodotin (ABT-414). METHODS: Case report. RESULTS: A 35-year-old man with glioblastoma multiforme participating in a phase III trial of the antibody-drug conjugate ABT-414 developed a large corneal abrasion from complications of MEK. Confocal imaging showed multiple large, round, hyperreflective lesions. Epithelial debridement was performed. Immunohistochemistry of the diseased epithelium showed IgG-positive granular cytoplasmic inclusions and increased cell apoptosis. With discontinuation of topical steroids, frequent lubrication, bandage contact lenses, and reduction in dose to maintenance therapy, the patient experienced symptomatic improvement. However, the MEK lesions recurred after debridement. CONCLUSIONS: ABT-414 accumulates in the basal corneal epithelium resulting in MEK due to increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief. PMID- 29794828 TI - Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. AB - : A phase 2, randomized, active-controlled study of initial antiretroviral therapy with bictegravir or dolutegravir in combination with emtricitabine and tenofovir alafenamide showed excellent efficacy. After 60 weeks of blinded treatment, participants switched to a single-tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide. Switching maintained viral suppression in all participants who remained on the study through 12 weeks in the open-label phase, and was safe and well tolerated. PMID- 29794827 TI - Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia. AB - OBJECTIVES: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition. DESIGN: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia. METHODS: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation. RESULTS: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4 cell count less than 500 cells/MUl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4 cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA >=1000 copies/ml, CD4 cell count less than 500 cells/MUl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART. CONCLUSION: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition. PMID- 29794829 TI - HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition. AB - BACKGROUND: Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS: A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5 +/- 6.0) underwent MRI scans of the brain. T1-weighted magnetization prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS: There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (beta = 0.17), non-white race (beta = 0.14), glomerular filtration rate (beta = -0.11), and the presence of diabetes (beta = 0.12). There were no interactions between HIV status and age (beta = -0.03) or between age and diabetes (beta = 0.07). However, the interaction between HIV infection and diabetes was significant (beta = 0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (beta = 0.15). CONCLUSION: In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions. PMID- 29794831 TI - Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa. AB - OBJECTIVES: To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART). DESIGN: Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum. SETTING: Peri-urban community, Cape Town, South Africa. PARTICIPANTS: HEU (n = 215) and HIV-unexposed (n = 306) children. MAIN OUTCOME MEASURES: Cognitive, motor and language development at median 13 (interquartile range 12-14) months of age: continuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85). RESULTS: Incidence of preterm delivery (<37 weeks) was similar among HEU and HIV unexposed children (11 vs. 9%, P = 0.31; median gestation 39 weeks); 48% were boys. Median breastfeeding duration was shorter among HEU vs. HIV-unexposed children (6 vs. 10 months). All HIV-infected mothers initiated lifelong ART (tenofovir-emtricitabine-efavirenz) antenatally. HEU (vs. HIV-unexposed) children had higher odds of cognitive delay [odds ratio (OR) 2.28 (95% confidence interval (CI) 1.13-4.60)] and motor delay [OR 2.10 (95% CI 1.03-4.28)], but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor development: compared with term HIV-unexposed children, term HEU children had similar odds of delay, preterm HIV-unexposed children had five-fold increased odds of delay (adjusted OR 4.73, 95% CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54). CONCLUSION: Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable. PMID- 29794830 TI - Abdominal fat depots, insulin resistance, and incident diabetes mellitus in women with and without HIV infection. AB - OBJECTIVE: The aim of this study was to determine the associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) mass with homeostatic model assessment-insulin resistance (HOMA-IR) and incidence of diabetes mellitus in women with and without HIV infection. DESIGN: Cross sectional design for associations between abdominal fat and HOMA-IR; longitudinal design for associations between abdominal fat and incident diabetes. METHODS: We assessed associations between dual X-ray absorptiometry scan-derived VAT and SAT with HOMA-IR in a subsample from the Women's Interagency HIV Study (n = 226 with and n = 100 without HIV) using linear regression. We evaluated associations of VAT, SAT and HOMA-IR with incident diabetes mellitus using Cox proportional hazards models. RESULTS: VAT mass was positively associated with log HOMA-IR in fully adjusted linear regression models stratified by HIV serostatus, including adjustment for SAT. During median follow-up of 10.6 years, incidence of diabetes was 1.63 [95% confidence interval (95% CI) 1.15-2.31] and 1.32 [95% CI 0.77-2.28] cases per 100 person-years in women with and without HIV (P = 0.52). In a fully adjusted model, baseline VAT (hazard ratio 2.64 per kg; 95% CI 1.14-6.12; P = 0.023) and SAT (hazard ratio 1.34 per kg; 95% CI 0.73-2.45; P = 0.35) were associated with incident diabetes, but the latter was not statistically significant. CONCLUSION: VAT mass was independently associated with HOMA-IR in women with and without HIV and was independently associated with future development of diabetes. PMID- 29794832 TI - Preference for injectable over oral HIV pre-exposure prophylaxis in public-sector primary-care clinics in Swaziland. AB - : Long-acting injectable (LAI) HIV pre-exposure prophylaxis (PrEP) may mitigate adherence challenges reported by young women in Southern Africa. We assessed preferences for PrEP in public-sector, primary care clinics in Swaziland. Among surveyed respondents, 75% (95% confidence interval = 65-83%) stated preference for LAI over oral PrEP; with no differences by sex, age, or sexual behavior (all P > 0.05). Notably, over 70% (95% confidence interval 58-82%) with current use of oral PrEP also stated preference for LAI PrEP. PMID- 29794833 TI - HIV solid organ transplantation: looking beyond HOPE. PMID- 29794834 TI - Lessons from the early HIV/AIDS epidemic. PMID- 29794835 TI - Workarounds as the Catalyst to Drive a Culture of Innovation in Neonatal Care. PMID- 29794836 TI - March 2018 Noteworthy News. PMID- 29794837 TI - Deepen Your Connection With NANN. PMID- 29794838 TI - Staff Nurse Perceptions of Open-Pod and Single Family Room NICU Designs on Work Environment and Patient Care. AB - BACKGROUND: Neonatal intensive care units have historically been constructed as open units or multiple-bed bays, but since the 1990s, the trend has been toward single family room (SFR) units. The SFR design has been found to promote family centered care and to improve patient outcomes and safety. The impact of the SFR design NICU on staff, however, has been mixed. PURPOSE: The purposes of this study were to compare staff nurse perceptions of their work environments in an open-pod versus an SFR NICU and to compare staff nurse perceptions of the impact of 2 NICU designs on the care they provide for patients/families. METHODS/SEARCH STRATEGY: A prospective cohort study was conducted. Questionnaires were completed at 6 months premove and again at 3, 9, and 15 months postmove. A series of 1-way analyses of variance were conducted to compare each group in each of the 8 domains. Open-ended questions were evaluated using thematic analysis. FINDINGS/RESULTS: The SFR design is favorable in relation to environmental quality and control of primary workspace, privacy and interruption, unit features supporting individual work, and unit features supporting teamwork; the open-pod design is preferable in relation to walking. IMPLICATIONS FOR PRACTICE: Incorporating design features that decrease staff isolation and walking and ensuring both patient and staff safety and security are important considerations. IMPLICATIONS FOR RESEARCH: Further study is needed on unit design at a microlevel including headwall design and human milk mixing areas, as well as on workflow processes. PMID- 29794839 TI - Clinical Outcomes in Preterm Infants Following Institution of a Delayed Umbilical Cord Clamping Practice Change. AB - BACKGROUND: Evidence supports a significant reduction in the incidence of intraventricular hemorrhage (IVH) in preterm infants receiving delayed umbilical cord clamping (DCC). PURPOSE: This study evaluated clinical feasibility, efficacy, and safety outcomes in preterm infants (<36 weeks' gestational age) who received DCC following a practice change implementation intended to reduce the incidence of IVH. METHODS: Infants receiving DCC (45-60 seconds) were compared with a sample of infants receiving immediate umbilical cord clamping (<15 seconds) in a retrospective chart review (N = 354). The primary outcome measure was the prevalence of IVH. Secondary safety outcome measures of 1- and 5-minute Apgar scores, axillary temperature on neonatal intensive care unit admission, and initial 24-hour bilirubin level were also evaluated. Gestational age was examined for its effect on outcomes. RESULTS: Although the small number of infants with IVH precluded the ability to detect statistical significance, our raw data suggest DCC is efficacious in reducing the risk for IVH. For infants 29 or less weeks' gestational age, admission axillary temperature was significantly higher in those who received DCC. No differences were found in 1- and 5-minute Apgar scores, 24-hour bilirubin level, or hematocrit level between the two groups. Infants more than 29 weeks' gestational age who received DCC had significantly higher 1-minute Apgar scores, temperature, and 24-hour bilirubin level. IMPLICATIONS FOR PRACTICE: Clinicians should advocate for the implementation of DCC as part of the resuscitative process for preterm neonates. IMPLICATIONS FOR RESEARCH: Future studies are needed to evaluate the effect of DCC on other clinical outcomes and to investigate umbilical cord milking as an alternative approach to DCC. PMID- 29794840 TI - Feeding Intervals in Premature Infants <=1750 g: An Integrative Review. PMID- 29794841 TI - A Succinct Critical Appraisal of Indications to Transanal TME. PMID- 29794842 TI - Factors Associated With Long Wait Times for Bariatric Surgery. AB - BACKGROUND: Despite its proven safety and efficacy, bariatric surgery is an underutilized therapy for severe obesity. Wait times for surgery are largely unexplored in the United States and may impact access to care. OBJECTIVE: To determine the amount of time between initial bariatric surgery clinic visit and operative date and identify factors associated with longer wait times. METHODS: A statewide clinical data registry was queried from 2006 to 2016 and 60,791 patients undergoing primary bariatric surgery were identified. Demographics, comorbidities, 30-day complications, and 1-year patient-reported outcomes were compared between shortest and longest wait time quartiles. Analyses were performed using Chi-square, t-test, and logistic regression. RESULTS: Median wait times for bariatric surgery increased from 86 to 159 days during the study period. Median wait times were <=67 days for the shortest wait time quartile and >=204 days for the longest wait time quartile. Factors independently associated with longer wait times included Medicaid insurance [odds ratio (OR) 3.02; 95% confidence interval (CI): 2.58-3.53], sleep apnea (OR 1.49; 95% CI: 1.41-1.58), psychological disorder (OR 1.25; 95% CI: 1.18-1.32), hyperlipidemia (OR 1.21; 95% CI: 1.14-1.28), smoking history (OR 1.11; 95% CI: 1.05-1.17), and white race (OR 0.665; 95% CI: 0.614-0.720). Preoperative weight loss, risk adjusted complication rates, postoperative self-reported weight loss, and comorbidity remission were similar between groups. CONCLUSIONS: Over the past decade, eligible patients are experiencing longer wait times when pursuing bariatric surgery. Complex patients with Medicaid insurance are experiencing the longest delay despite similar outcomes and preoperative weight loss. Policies that delay surgery should be re examined. PMID- 29794843 TI - Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (S LYMPHA) for the Prevention of Breast Cancer-Related Clinical Lymphedema After Axillary Lymph Node Dissection. AB - OBJECTIVE: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients. BACKGROUND: LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services. METHODS: All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S LYMPHA. RESULTS: A total of 380 patients were included in the analysis. Median follow-up time was 15 (1-32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P = 0.001; odds ratio 0.12 (0.03-0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis. CONCLUSIONS: S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery. PMID- 29794845 TI - Overlapping Surgery in Pediatric Surgical Care: Is It a Safe and Cost-effective Practice? PMID- 29794844 TI - The Impact of an ICU "Bed Ahead" Policy on ED Length of Stay and Patient Outcomes. AB - OBJECTIVE: To assess the impact of preassigning a single bed in the surgical intensive care unit (SICU) for the next trauma admission. BACKGROUND: Prolonged emergency department (ED) dwell time before admission to a critical care unit has an adverse effect on patient outcomes and is often due to the lack of an available bed in the intensive care unit (ICU). METHODS: A "Bed Ahead" policy was instituted at an urban level 1 Trauma Public Safety Net Teaching Hospital to preassign 1 SICU bed for the next trauma patient who warrants a critical care admission. A retrospective review of all trauma patients admitted to the SICU before and after implementation of this policy was performed to assess the impact on ED dwell time, ICU and hospital lengths of stay, complications, and in hospital mortality. RESULTS: ED length of stay (ED-LOS); ICU length of stay (ICU LOS); hospital length of stay (HLOS); complications; and in-hospital mortality were compared before (PRE) and after (POST)implementation of the Bed Ahead policy. Statistically significant improvements were seen in the POST period for ED-LOS, HLOS, complications, and in-hospital mortality. CONCLUSIONS: Preassigning 1 ICU for the yet to arrive next injured patient decreases ED dwell times, complications, HLOS, and in-hospital mortality. PMID- 29794846 TI - Prognostic Value of Lymph Node Yield on Overall Survival in Esophageal Cancer Patients: A Systematic Review and Meta-analysis. AB - OBJECTIVE: This meta-analysis determines whether increased lymph node yield improves survival in patients with esophageal cancer undergoing esophagectomy with or without neoadjuvant therapy. BACKGROUND: Esophagectomy involves resection of the esophagus and surrounding lymph nodes, which are commonly the first stations of cancer spread. The extent of lymphadenectomy during esophagectomy remains controversial, with several studies publishing conflicting results, especially in the era of neoadjuvant therapy. METHODS: An electronic literature search was undertaken using Embase, Medline, and the Cochrane library databases (2000 to 2017). Articles with esophageal cancer patients undergoing esophagectomy with lymphadenectomy and investigating the effects of low and high lymph node yield on overall survival and disease-free survival were included. Meta-analysis of data was conducted using a random effects model. If the study divided the cohort into multiple groups based on lymph node yield, survival was compared between the lowest and highest lymph node yield groups. In addition to analysis of the entire cohort, subset analysis of only those patients receiving neoadjuvant therapy was also performed. RESULTS: A total of 26 studies were included in this meta-analysis with a follow-up ranging from 15 to 94 months. For the analysis of overall survival, 23 studies were included. A meta-analysis showed that overall survival significantly improved in the high lymph node yield group [hazard ratio (HR) = 0.81; 95% confidence interval (95% CI) = 0.74-0.87; P < 0.01]. In the 10 studies describing disease-free survival, this was significantly improved in the high lymph node yield group (HR = 0.72; 95% CI = 0.62-0.84; P < 0.01). Subset analysis of neoadjuvant-treated patients demonstrated a survival benefit of high lymph node yield on overall survival (HR = 0.82; 95% CI = 0.73-0.92; P < 0.01). CONCLUSION: This meta-analysis demonstrates the benefit of an increased lymph node yield from esophagectomy on overall and disease-free survival. In addition, a survival benefit of a high lymph node yield was demonstrated in patients receiving neoadjuvant therapy followed by esophagectomy. PMID- 29794848 TI - Clinical and Prognostic Features of Patients With Esophageal Cancer and Multiple Primary Cancers. PMID- 29794847 TI - Data-driven Development of ROTEM and TEG Algorithms for the Management of Trauma Hemorrhage: A Prospective Observational Multicenter Study. AB - OBJECTIVE: Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs). BACKGROUND: Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013. METHODS: To identify significant VHA parameters capable of detecting TIC (defined as INR > 1.2), hypofibrinogenemia (< 2.0 g/L), and thrombocytopenia (< 100 x10/L), univariate regression models were constructed. Area under the curve (AUC) was calculated, and threshold values for TEG and ROTEM parameters with 70% sensitivity were included in the algorithms. RESULTS: A total of, 2287 adult trauma patients (ROTEM: 2019 and TEG: 968) were enrolled. FIBTEM clot amplitude at 5 minutes (CA5) had the largest AUC and 10 mm detected hypofibrinogenemia with 70% sensitivity. The corresponding value for functional fibrinogen (FF) TEG maximum amplitude (MA) was 19 mm. Thrombocytopenia was similarly detected using the calculated threshold EXTEM-FIBTEM CA5 30 mm. The corresponding rTEG-FF TEG MA was 46 mm. TIC was identified by EXTEM CA5 41 mm, rTEG MA 64 mm (80% sensitivity). For hyperfibrinolysis, we examined the relationship between viscoelastic lysis parameters and clinical outcomes, with resulting threshold values of 85% for EXTEM Li30 and 10% for rTEG Ly30.Based on these analyses, we constructed algorithms for ROTEM, TEG, and CCTs to be used in addition to ratio driven transfusion and tranexamic acid. CONCLUSIONS: We describe a systematic approach to define threshold parameters for ROTEM and TEG. These parameters were incorporated into algorithms to support data-driven adjustments of resuscitation with therapeutics, to optimize damage control resuscitation practice in trauma. PMID- 29794849 TI - Alignment of Personality Is Associated With Increased Intraoperative Entrustment. AB - OBJECTIVE: To determine the association between intraoperative entrustment and personality alignment. SUMMARY BACKGROUND DATA: For surgical residents, achieving operative autonomy has become increasingly difficult. The impact of faculty resident operative interactions in accomplishing this goal is not well understood. We hypothesized that if operative dyads (faculty and resident) had personality alignment or congruency, then resident entrustment in the operating room would increase. METHODS: We completed a retrospective analysis of 63 operations performed from September 2015 to August 2016. Operations were scored using OpTrust, a validated tool that assesses progressive entrustment of responsibility to surgical residents in the operating room. All dyads were classified as having congruent or incongruent personality alignment as measured by promotion or prevention orientation using the regulatory focus questionnaire. The association between personality congruence and OpTrust scores was identified using multivariable linear regression. RESULTS: A total of 35 congruent dyads and 28 incongruent dyads were identified. Congruent dyads had a higher percentage of "very difficult" cases (33.3 vs. 7.4%, P = 0.017), female residents (37.1 vs. 14.3%, P = 0.042) and faculty with fewer years of experience (10.4 vs. 14.8%, P = 0.028) than incongruent dyads. In addition to post-graduate year level, dyad congruency was independently associated with a 0.88 increase (95% CI [0.27-1.49], P = 0.006) in OpTrust scores (overall range 2-8), after adjusting for case difficulty, faculty experience, and post-graduate year. CONCLUSIONS: Congruent operative dyads are associated with increased operative entrustment as demonstrated by increased OpTrust scores. Developing awareness and strategies for addressing incongruence in personality in the operative dyad is needed. PMID- 29794850 TI - Surgeon Age in Relation to Prognosis After Esophageal Cancer Resection. PMID- 29794851 TI - Added Value of Body Fat Distribution in Predicting Clinically Significant Pancreatic Fistula in the a-FRS Following Pancreatoduodenectomy Currently Unclear. PMID- 29794852 TI - Advances in pharmacokinetic modeling: target controlled infusions in the obese. AB - PURPOSE OF REVIEW: The use of conventional pharmacokinetic parameters sets 'models' derived from nonobese patients has proven inadequate to administer intravenous anesthetics in the obese population and is commonly associated with higher than anticipated plasma propofol concentrations when used with target (plasma or effect site) controlled infusion pumps. In this review we will describe recent modeling strategies to characterize the disposition of intravenous anesthetics in the obese patient and will show clinically relevant aspects of new model's performance in the obese population. RECENT FINDINGS: Because clearance of a drug increases in a nonlinear manner with weight, nonlinear relationships better scale infusion rates between lean and obese individuals. Allometric concepts have been successfully used to describe size related nonlinear changes in clearances. Other nonlinear scaling options include the use of descriptors such as body surface area, lean body weight, fat-free mass, and normal fat mass. Newer pharmacokinetic models, determined from obese patient data, have been developed for propofol and remifentanil using allometric concepts and comprehensive size descriptors. SUMMARY: Pharmacokinetic models to perform target-controlled infusion in the obese population should incorporate descriptors that reflect with greater precision the influence of body composition in volumes and clearances of each drug. It is our hope that commercially available pumps will soon incorporate these new models to improve the performance of this technique in the obese population. PMID- 29794853 TI - Endovascular thrombectomy in acute ischemic stroke: new treatment guide. AB - PURPOSE OF REVIEW: Recent randomized clinical trials (RCTs) have demonstrated strong efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) from large vessel occlusions (LVO). SIESTA, AnSTROKE, GOLIATH showed no deleterious effects of general anesthesia on patient outcome after EVT compared with conscious sedation. DAWN and DEFUSE 3 are extending the time window for EVT up to 24 h in carefully selected patients. This review discusses the current literature on the rapidly expanding subject of endovascular stroke therapy and optimal anesthetic management. RECENT FINDINGS: Recent retrospective studies of RCT data sets show that general anesthesia is associated with negative clinical outcome in AIS patients undergoing EVT when compared with sedation. Two of the possible mechanisms of this finding are systolic hypotension and hypocapnia. SIESTA, AnSTROKE, GOLIATH showed no difference in short-term clinical outcome between EVT patients treated with general anesthesia versus conscious sedation. DAWN and DEFUSE 3 demonstrated improved functional outcomes after EVT in those treated up to 24 h after selection with perfusion imaging, increasing the number of patients eligible for EVT. SUMMARY: Effective reperfusion with stent retriever technology, careful patient selection using perfusion imaging, and careful use of anesthetic technique affect outcome. PMID- 29794854 TI - Emerging evidence for antidepressant actions of anesthetic agents. AB - PURPOSE OF REVIEW: After decades without substantial advances, multiple novel antidepressants show promise against treatment-resistant depression. Interestingly, many of these are anesthetics. The purpose of this review is to discuss the evidence for the antidepressant effects of ketamine, nitrous oxide, isoflurane and propofol and to consider potential clinical, administrative and research implications for anesthesiologists. RECENT FINDINGS: Ketamine has acute, transient antidepressant and antisuicidal effects. Nitrous oxide has also shown antidepressant efficacy. There are converging preclinical and clinical data that isoflurane (and perhaps propofol), dosed to burst suppression, has relatively rapid, robust and durable antidepressant effects and lacks the adverse effects associated with electroconvulsive therapy (ECT). SUMMARY: Several anesthetics show promise as novel antidepressants. Ketamine is the most well studied. Anesthetic-induced burst-suppression may provide an alternative to ECT that lacks adverse cognitive effects. Further study is necessary to better understand how these drugs work and how they might be used as effective antidepressant therapy. PMID- 29794856 TI - New horizons in anesthetic clinical pharmacology, patient outcomes and perioperative neuromonitoring. PMID- 29794857 TI - Revisiting the Anteroinferior Iliac Spine: Is the Subspine Pathologic? A Clinical and Radiographic Evaluation. AB - BACKGROUND: Subspine impingement is a recognized source of extraarticular hip impingement. Although CT-based classification systems have been described, to our knowledge, no study has evaluated the morphology of the anteroinferior iliac spine (AIIS) with plain radiographs nor to our knowledge has any study compared its appearance between plain radiographs and CT scan and correlated AIIS morphology with physical findings. Previous work has suggested a correlation of AIIS morphology and hip ROM but this has not been clinically validated. Furthermore, if plain radiographs can be found to adequately screen for AIIS morphology, CT could be selectively used, limiting radiation exposure. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the prevalence of AIIS subtypes in a cohort of patients with symptomatic femoroacetabular impingement; (2) to compare AP pelvis and false profile radiographs with three-dimensional (3-D) CT classification; and (3) to correlate the preoperative hip physical examination with AIIS subtypes. METHODS: A retrospective study of patients undergoing primary hip arthroscopy for femoroacetabular impingement syndrome was performed. Between February 2013 and November 2016, 601 patients underwent hip arthroscopy. To be included here, each patient had to have undergone a primary hip arthroscopy for the diagnosis of femoroacetabular impingement syndrome. Each patient needed to have an interpretable set of plain radiographs consisting of weightbearing AP pelvis and false profile radiographs as well as full documentation of physical findings in the medical record. Patients who additionally had a CT scan with 3-D reconstructions were included as well. During the period in question, it was the preference of the treating surgeon whether a preoperative CT scan was obtained. A total of 145 of 601 (24%) patients were included in the analysis; of this cohort, 54% (78 of 145) had a CT scan and 63% (92 of 145) were women with a mean age of 31 +/- 10 years. The AIIS was classified first on patients in whom the 3-D CT scan was available based on a previously published 3-D CT classification. The AIIS was then classified by two orthopaedic surgeons (TGM, MRK) on AP and false profile radiographs based on the position of its inferior margin to a line at the lateral aspect of the acetabular sourcil normal to vertical. Type I was above, Type II at the level, and Type III below this line. There was fair interrater agreement for AP pelvis (kappa = 0.382; 95% confidence interval [CI], 0.239 0.525), false profile (kappa = 0.372; 95% CI, 0.229-0.515), and 3-D CT (kappa = 0.325; 95% CI, 0.156-0.494). There was moderate to almost perfect intraobserver repeatability for AP pelvis (kappa = 0.516; 95% CI, 0.284-0.748), false profile (kappa = 0.915; 95% CI, 0.766-1.000), and 3-D CT (kappa = 0.915; 95% CI, 0.766 1.000). The plane radiographs were then compared with the 3-D CT scan classification and accuracy, defined as the proportion of correct classification out of total classifications. Preoperative hip flexion, internal rotation, external rotation, flexion adduction, internal rotation, subspine, and Stinchfield physical examination tests were compared with classification of the AIIS on 3-D CT. Finally, preoperative hip flexion, internal rotation, and external rotation were compared with preoperative lateral center-edge angle and alpha angle. RESULTS: The prevalence of AIIS was 56% (44 of 78) Type I, 39% (30 of 78) Type II, and 5% (four of 78) Type III determined from the 3-D CT classification. For the plain radiographic classification, the distribution of AIIS morphology was 64% (93 of 145) Type I, 32% (46 of 145) Type II, and 4% (six of 145) Type III on AP pelvis and 49% (71 of 145) Type I, 48% (70 of 145) Type II, and 3% (four of 145) Type III on false profile radiographs. False profile radiographs were more accurate than AP pelvis radiographs for classification when compared against the gold standard of 3-D CT at 98% (95% CI, 96-100) versus 80% (95% CI, 75-85). The false profile radiograph had better sensitivity for Type II (97% versus 47%, p < 0.001) and specificity for Types I and II AIIS (97% versus 53%, p < 0.001; 98% versus 90%, p = 0.046) morphology compared with AP pelvis radiographs. There was no correlation between AIIS type as determined by 3-D CT scan and hip flexion (rs = -0.115, p = 0.377), internal rotation (rs = 0.070, p = 0.548), flexion adduction internal rotation (U = 72.00, p = 0.270), Stinchfield (U = 290.50, p = 0.755), or subspine tests (U = 319.00, p = 0.519). External rotation was weakly correlated (rs = 0.253, p = 0.028) with AIIS subtype. Alpha angle was negatively correlated with hip flexion (r = -0.387, p = 0.002) and external rotation (r = -0.238, p = 0.043) and not correlated with internal rotation (r = -0.068, p = 0.568). CONCLUSIONS: The findings in this study suggest the false profile radiograph is superior to an AP radiograph of the pelvis in evaluating AIIS morphology. Neither preoperative hip internal rotation nor impingement tests correlate with AIIS type as previously suggested questioning the utility of the AIIS classification system in identifying pathologic AIIS anatomy. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 29794858 TI - Does Orthopaedic Outpatient Care Reduce Emergency Department Utilization After Total Joint Arthroplasty? AB - BACKGROUND: Emergency department (ED) visits after elective surgical procedures are a potential target for interventions to reduce healthcare costs. More than 1 million total joint arthroplasties (TJAs) are performed each year with postsurgical ED utilization estimated in the range of 10%. QUESTIONS/PURPOSES: We asked whether (1) outpatient orthopaedic care was associated with reduced ED utilization and (2) whether there were identifiable factors associated with ED utilization within the first 30 and 90 days after TJA. METHODS: An analysis of adult TRICARE beneficiaries who underwent TJA (2006-2014) was performed. TRICARE is the insurance program of the Department of Defense, covering > 9 million beneficiaries. ED use within 90 days of surgery was the primary outcome and postoperative outpatient orthopaedic care the primary explanatory variable. Patient demographics (age, sex, race, beneficiary category), clinical characteristics (length of hospital stay, prior comorbidities, complications), and environment of care were used as covariates. Logistic regression adjusted for all covariates was performed to determine factors associated with ED use. RESULTS: We found that orthopaedic outpatient care (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.68-0.77) was associated with lower odds of ED use within 90 days. We also found that index hospital length of stay (OR, 1.07; 95% CI, 1.04-1.10), medical comorbidities (OR, 1.16; 95% CI, 1.08-1.24), and complications (OR, 2.47; 95% CI, 2.24-2.72) were associated with higher odds of ED use. CONCLUSIONS: When considering that at 90 days, only 3928 patients sustained a complication, a substantial number of ED visits (11,486 of 15,414 [75%]) after TJA may be avoidable. Enhancing access to appropriate outpatient care with improved discharge planning may reduce ED use after TJA. Further research should be directed toward unpacking the situations, outside of complications, that drive patients to access the ED and devise interventions that could mitigate such behavior. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 29794859 TI - Residency Diary: Every Resident Needs a Lighthouse. PMID- 29794860 TI - CORR Insights(r): Is Cemented or Cementless Femoral Stem Fixation More Durable in Patients Older Than 75 Years of Age? A Comparison of the Best-performing Stems. PMID- 29794855 TI - An overview of the cannabinoid type 2 receptor system and its therapeutic potential. AB - PURPOSE OF REVIEW: This narrative review summarizes recent insights into the role of the cannabinoid type 2 (CB2) receptor as potential therapeutic target in neuropathic pain and neurodegenerative conditions. RECENT FINDINGS: The cannabinoid system continues to receive attention as a therapeutic target. The CB2 receptor is primarily expressed on glial cells only when there is active inflammation and appears to be devoid of undesired psychotropic effects or addiction liability. The CB2 receptor has been shown to have potential as a therapeutic target in models of diseases with limited or no currently approved therapies, such as neuropathic pain and neurodegenerative conditions such as Alzheimer's disease. SUMMARY: The functional involvement of CB2 receptor in neuropathic pain and other neuroinflammatory diseases highlights the potential therapeutic role of drugs acting at the CB2 receptor. PMID- 29794861 TI - CORR Insights(r): What is the Normal Trajectory of Interleukin-6 and C-reactive Protein in the Hours and Days Immediately After TKA? PMID- 29794862 TI - Editor's Spotlight/Take 5: Resident Participation is Not Associated With Worse Outcomes After TKA. PMID- 29794863 TI - CORR Insights(r): Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry. PMID- 29794864 TI - CORR Insights(r): Soft Tissue Sarcoma of the Extremities: What Is the Value of Treating at High-volume Centers? PMID- 29794865 TI - CORR Insights(r): Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and Is Not a Spontaneous Model Metastasis: A Mouse Osteosarcoma Model. PMID- 29794866 TI - CORR Insights(r): Revisiting the Anteroinferior Iliac Spine: Is the Subspine Pathologic? A Clinical and Radiographic Evaluation. PMID- 29794867 TI - CORR Insights(r): Does the Watson-Jones or Modified Smith-Petersen Approach Provide Superior Exposure for Femoral Neck Fracture Fixation? PMID- 29794868 TI - Editorial: Can Surgeons Delegate Informed Consent? As Goes Pennsylvania, So Goes the Nation (or Not). PMID- 29794869 TI - The Clinical Significance of a Small Component of Choriocarcinoma in Testicular Mixed Germ Cell Tumor (MGCT). AB - The clinical significance of limited choriocarcinoma in a malignant mixed germ cell tumor (MGCT) is unknown. Men with a MGCT with <=5% choriocarcinoma at radical orchiectomy (RO) between 2000 and 2016 from our consult service were studied. Of 50 men in our cohort, we had clinical information for 30 men. Median follow-up was 41 months (1 to 168 mo). Median tumor size was 4.5 cm (1.1 to 8.0 cm). In total, 22/30 (73%) cases were pT1, 6/30(20%) cases were pT2, and 2/30 (7%) cases were pT3. In total, 4/30(13%) cases had lymph node metastases and 2/30 (7%) cases had distant metastases at the time of RO. In 30 cases with RO we had information on immediate postorchiectomy treatment: 14/30 (46.7%) active surveillance, 4/30 (13.3%) retroperitoneal lymph node dissection, 10/30 (33.3%) chemotherapy (chemotherapy), 1/30 (3.3%) retroperitoneal lymph node dissection followed by chemotherapy, and 1/30 (3.3%) resection of a distant metastasis. Preoperative serum human chorionic gonadotropin (hCG) levels ranged between 0.1 and 60,715 mIU/mL (mean, 4796; median, 485). One patient had an hCG level of 6367 mIU/mL and another 60,715 mIU/mL with the remaining cases <5000 mIU/mL. In total, 4/30 (13%) patients had elevated serum markers after surgery, 3 of them normalized following chemotherapy while the fourth one continued to have elevated serum alpha fetoprotein levels after chemotherapy. All patients were alive at last follow-up. In total, 7/30 (23.3%) patients subsequently developed metastatic disease to lymph nodes or distal organs, the histology of the metastasis consisted mainly of teratoma and yolk sac tumor. Embryonal carcinoma was present in 2 metastatic sites. One lung metastasis was suggestive for choriocarcinoma. Definitive choriocarcinoma was not present in any of the metastasis. A small component of choriocarcinoma in a MGCT is typically associated with relatively low-level elevations of serum hCG levels, and is not associated with aggressive disease. The presence of limited choriocarcinoma (<=5%) does not add to the prognostic information provided by standard TNM staging, which uses levels of serum markers (hCG, alpha fetoprotein, lactate dehydrogenase) as surrogates for extent of disease. PMID- 29794870 TI - Concordance of PD-L1 Expression Between Core Biopsy and Resection Specimens of Non-Small Cell Lung Cancer. AB - The heterogeneity of programmed death ligand 1 (PD-L1) expression in non-small cell lung carcinomas (NSCLCs) is well studied; however, the method of tissue sampling needed to obtain adequate diagnostic material has not been established. This study aimed to determine whether core needle biopsy provides sufficient tissue for accurate PD-L1 evaluation despite tumor heterogeneity. A retrospective analysis comparing tumoral expression of PD-L1 in 51 lung core biopsies to subsequent resection specimens was performed. Scoring of membranous staining was categorized as 0%, 1% to 49%, and >=50% of tumor cells. Staining >=50% tumoral PD L1 expression was detected in 8/51 (15.7%) of core biopsies and 8/51 (15.7%) of resection specimens. Core biopsy and resection results were concordant in 92.2% of cases (kappa, 0.70; 95% confidence interval, 0.43-0.98). Therefore, despite tumor heterogeneity, detection of tumoral PD-L1 expression in NSCLC appears to be largely concordant between core biopsies and resection specimens, with the caveat that it may be helpful to reassess resection specimens for low-level staining. These findings suggest that core biopsy may be adequate for determining PD-L1 expression in NSCLC. PMID- 29794871 TI - ALK-rearranged Tumors are Highly Enriched in the STUMP Subcategory of Uterine Tumors. AB - Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogenous. Recent data suggest uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as STUMPs, but the extent to which this occurs has not been examined. We identified 60 female patients with tumors previously diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid features, although limited in some cases, were present in all 6 ALK IHC positive tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3' ALK signals, an unusual FISH pattern not previously described in uterine IMTs. Two patients developed recurrent disease and were treated with ALK-targeted therapy with initial response. Our data demonstrate that a significant proportion of uterine and cervical tumors considered to be STUMPs are ALK-positive by IHC and FISH. Future screening of all uterine and cervical mesenchymal tumors under consideration for the diagnosis of STUMP, particularly those with myxoid features, is recommended to identify ALK-rearranged IMTs that could potentially be treated with targeted therapy using tyrosine kinase inhibitors. PMID- 29794872 TI - A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction. AB - Neuroblastoma (NB) is the most common extracranial solid tumor in children with contrasting outcomes. Precise risk assessment contributes to prognosis prediction, which is critical for treatment strategy decisions. In this study, we developed a 3-protein predictor model, including the neural stem cell marker Msi1, neural differentiation marker ID1, and proliferation marker proliferating cell nuclear antigen (PCNA), to improve clinical risk assessment of patients with NB. Kaplan-Meier analysis in the microarray data (GSE16476) revealed that low expression of ID1 and high expression of Msi1 and PCNA were associated with poor prognosis in NB patients. Combined application of these 3 markers to constitute a signature further stratified NB patients into different risk subgroups can help obtain more accurate prediction performance. Survival prognostic power of age and Msi1_ID1_PCNA signature by receiver operating characteristics analysis showed that this signature predicted more effectively and sensitively compared with classic risk stratification system, compensating for the deficiency of the prediction function of the age. Furthermore, we validated the expressions of these 3 proteins in neuroblastic tumor spectrum tissues by immunohistochemistry revealed that Msi1 and PCNA exhibited increased expression in NB compared with intermedial ganglioneuroblastoma and benign ganglioneuroma, whereas ID1 levels were reduced in NB. In conclusion, we established a robust risk assessment predictor model based on simple immunohistochemistry for therapeutic decisions of NB patients. PMID- 29794873 TI - Genomic Fusions in Pigmented Spindle Cell Nevus of Reed. AB - Recent molecular studies of spitzoid neoplasms have identified mutually exclusive kinase fusions involving ROS1, ALK, RET, BRAF, NTRK1, MET, and NTRK3 as early initiating genomic events. Pigmented spindle cell nevus (PSCN) of Reed is a morphologic variant of Spitz and may be very diagnostically challenging, having histologic features concerning for melanoma. Their occurrence in younger patients, lack of association to sun exposure, and rapid early growth phase similar to Spitz nevi suggest fusions may also play a significant role in these lesions. However, to date, there is little data in the literature focused on the molecular characterization of PSCN of Reed with next-generation sequencing. We analyzed a total of 129 melanocytic neoplasms with RNA sequencing including 67 spitzoid neoplasms (10 Spitz nevi, 44 atypical Spitz tumors, 13 spitzoid melanomas) and 23 PSCN of Reed. Although only 2 of 67 (3.0%) of spitzoid lesions had NTRK3 fusions, 13 of 23 (57%) of PSCN of Reed harbored NTRK3 fusions with 5' partners ETV6 (12p13) in 2 cases and MYO5A (15q21) in 11 cases. NTRK3 fusions were confirmed with a fluorescent in situ hybridization break-apart probe. The presence of a NTRK3 fusion correlated with younger age (P=0.021) and adnexal extension (P=0.001). Other minor fusions identified in PSCN of Reed included MYO5A-MERTK (2), MYO5A-ROS1, MYO5A-RET, and ETV6-PITX3 leading to a total of 78% with fusions. Our study suggests that the majority of PSCN of Reed are the result of genomic fusions, and the most frequent and characteristic genomic aberration is an NTRK3 fusion. PMID- 29794874 TI - Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs: A Comprehensive Review of Phase 3 Efficacy and Safety. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease modifying antirheumatic drugs. METHODS: A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed. RESULTS: Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib. CONCLUSIONS: Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. PMID- 29794875 TI - Erosive Gouty Arthropathy Resulting in a Telescoping Digit. PMID- 29794876 TI - Prevalence and Associations of Avascular Necrosis of the Hip in a Large Well characterized Cohort of Patients With Inflammatory Bowel Disease. AB - OBJECTIVES: Avascular necrosis (AVN) is associated with significant morbidity potentially causing severe pain and debility; patients with inflammatory bowel disease (IBD) have a higher prevalence of AVN compared with non-IBD populations. The purpose of our study was to determine the prevalence of AVN in our IBD population and to evaluate these subjects for the presence of clinical characteristics associated with AVN on computed tomography (CT) imaging. METHODS: In 1313 IBD patients with abdomen/pelvis CT scans, we identified 27 patients (2.1%) with CT findings consistent with AVN. Through historical chart review, we confirmed that most patients had prior exposure to steroids, although 2 patients had no documented steroid exposure at all. RESULTS: We found that 59% of the concurrent radiology reports did not comment on the presence of AVN, suggesting that incidental CT findings of AVN among IBD patients are likely underreported. Notably, we found that 63% of these cases had documented complaints of low-back and/or hip pain. Using logistic regression, we found an association between anti neutrophil cytoplasmic antibody-positive status across IBD (P = 0.007) and a smoking history in Crohn disease (P = 0.03) with the presence of AVN. CONCLUSIONS: We found that a significant proportion of IBD patients with AVN are reported in their records as not having hip or low-back pain, and review of CT imaging under dedicated bone windows may identify AVN among this population. Our findings also suggest that additional etiological factors, beyond corticosteroids, contribute to the development of AVN in IBD. Further investigation is warranted regarding the mechanisms associated with AVN in IBD. PMID- 29794877 TI - Tofacitinib for the Treatment of Refractory Polymyositis. PMID- 29794878 TI - Trigeminal ganglion transcriptome analysis in 2 rat models of medication-overuse headache reveals coherent and widespread induction of pronociceptive gene expression patterns. AB - We attempted to gather information on the pathogenesis of medication-overuse headache, as well as on the neurochemical mechanisms through which symptomatic medication overuse concurs to headache chronification. Transcriptional profiles were therefore evaluated as an index of the homeostasis of the trigeminovascular system in the trigeminal ganglion of female rats exposed for 1 month to daily oral doses of eletriptan or indomethacin. We report that both drug treatments change trigeminal ganglion gene expression to a similar extend. Of note, qualitative transcriptomic analysis shows that eletriptan and indomethacin prompt nearly identical, increased expression of genes coding for proteins involved in migraine pathogenesis and central pain sensitization such as neuropeptides, their cognate receptors, prostanoid, and nitric oxide-synthesizing enzymes, as well as TRP channels. These genes, however, were not affected in thoracic dorsal root ganglia. Of note, lowering of orofacial nociceptive thresholds, as well as forepaw hyperalgesia occurred in both indomethacin- and eletriptan-treated rats. Our study reveals that chronic rat exposure to 2 acute headache medications with completely different mechanisms of action prompts pain sensitization with highly similar induction of pronociceptive genes selectively within the trigeminal ganglion. Data further our understanding of medication-overuse headache pathogenesis and provide hints for specific mechanism-based treatment options. PMID- 29794879 TI - Should thoracic paravertebral blocks be used to prevent chronic postsurgical pain after breast cancer surgery? A systematic analysis of evidence in light of IMMPACT recommendations. AB - The role of thoracic paravertebral block (PVB) in preventing chronic postsurgical pain (CPSP) after breast cancer surgery (BCS) has gained interest, but existing evidence is conflicting, and its methodological quality is unclear. This meta analysis evaluates efficacy of PVB, compared with Control group, in preventing CPSP after BCS, in light of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. Electronic databases were searched for randomized trials comparing PVB with Control group for CPSP prevention after BCS. Eligible trials were assessed for adherence to IMMPACT recommendations. The primary outcomes were CPSP at 3 and 6 months, whereas secondary outcomes were PVB-related complications. Data were pooled and analyzed using random-effects modelling. Trial sequential analysis was used to evaluate evidence conclusiveness. Data from 9 studies (604 patients) were analyzed. The median (range) of IMMPACT recommendations met in these trials was 9 (5, 15) of 21. Paravertebral block was not different from Control group in preventing CPSP at 3 months, but was protective at 6 months, with relative risk reduction (95% confidence interval) of 54% (0.24-0.88) (P = 0.02). Meta-regression suggested that the relative risk of CPSP was lower when single-injection (R = 1.00, P < 0.001) and multilevel (R = 0.71, P = 0.01) PVB were used. Trial sequential analysis revealed that 6-month analysis was underpowered by at least 312 patients. Evidence quality was moderate according to the GRADE system. Evidence suggests that multilevel single-injection PVB may be protective against CPSP at 6 months after BCS, but methodological limitations are present. Larger trials observing IMMPACT recommendations are needed to confirm this treatment effect and its magnitude. PMID- 29794880 TI - Improving accuracy for intraocular lens selection in cataract surgery. AB - PURPOSE OF REVIEW: To perform a literature review of articles published between 2016 and 2017 to assess recent advances in intraocular lens (IOL) selection. RECENT FINDINGS: A literature review revealed five areas of recent study including advances in biometric technology, formula selection for challenging eyes, accurate astigmatic correction, adjustment of IOL calculations for postrefractive eyes with and without prerefractive surgery data, and use of intraoperative IOL calculations. SUMMARY: As cataract surgery continues to be one of the most commonly performed surgeries in the United States, it is important to ensure that the most accurate technology, IOL formula, and surgical planning is utilized. PMID- 29794882 TI - Clinical Immersion: An Approach for Fostering Cross-disciplinary Communication and Innovation in Nursing and Engineering Students. AB - A faculty team from nursing and chemical engineering developed a course that brought together students from each discipline for cross-disciplinary, team-based clinical immersion and collaboration. Health care processes and devices are rapidly changing, and nurses are uniquely positioned to be bedside innovators to improve patient care delivery. During each clinical immersion, the student teams rotated through various hospital units where they identified problems and worked together in the university's makerspace (iMaker Space) to design and build prototypes to improve health outcomes. Data from the Critical thinking Assessment Test provided evidence of gains in critical-thinking and problem-solving skills, while the problems identified in the clinical setting and prototypes developed demonstrated the impact of bringing nursing and engineering students together to design innovations. When challenged to identify authentic problems during their clinical immersion, the teams of nursing and engineering students proposed creative solutions and developed commercially viable prototypes. PMID- 29794881 TI - Herpes zoster ophthalmicus: acute keratitis. AB - PURPOSE OF REVIEW: Herpes zoster is a common condition, and involvement of the trigeminal nerve results in herpes zoster ophthalmicus (HZO). Acute keratitis is one of the most common of these ocular complications associated with HZO. The findings associated with and the management of acute zoster keratitis will be reviewed. RECENT FINDINGS: The incidence rate of herpes zoster has been on the rise over the past several decades. At the same time, the average patient age at presentation is declining with similar trends also seen in HZO. The cause of these changes has yet to be determined. Our understanding of corneal involvement in HZO continues to evolve with new imaging demonstrating viral particles within keratocytes in a case of zoster stromal keratitis. New medications such as topical ganciclovir are also helping to better manage acute zoster keratitis that is unresponsive to oral antiviral therapy. SUMMARY: Acute zoster keratitis can lead to permanent vision loss. Early diagnosis and management may help reduce these potentially devastating complications. Oral and topical antiviral medications can play a role in managing the acute disease, and herpes zoster vaccinations are important for prevention of disease. Further research must be done to establish standards for treatment of anterior segment complications from herpes zoster. PMID- 29794883 TI - Educational Preparation for Clinical Practice: Reflections of Newly Graduated RNs. AB - Preparedness of newly graduated RNs to provide safe, competent patient care is a significant concern because of increasing work demands and complexities in health care systems. This qualitative study explored the perceptions of newly graduated RNs about how their educational experiences as prelicensure students prepared them to enter the nursing workforce. Face-to-face, semi structured interviews were conducted with 10 RNs who held baccalaureate degrees, were employed in acute care settings, and practiced for 1 to 2 years. Analysis of the interview data revealed that nursing education programs did not adequately prepare graduates for their multifaceted roles and responsibilities as RNs. The participants offered recommendations for faculty use in prelicensure nursing programs to better prepare students for successful transition into clinical practice. Nursing faculty should implement practice-oriented educational experiences to facilitate students to assume professional roles and responsibilities when they enter the nursing workforce. PMID- 29794884 TI - Nurse Preceptor Perceptions of Nursing Student Progress Toward Readiness for Practice. AB - New nurses are often perceived as not meeting expectations for safe nursing practice. Nurse educators need to identify student learning and professional development needs as students progress toward practice. The purpose of the study was to determine the strengths and weaknesses of senior-level nursing students related to readiness for practice before graduation. Using a descriptive, exploratory design, nurse preceptors evaluated the degree to which their assigned senior nursing student was meeting expectations for readiness for nursing practice. Survey items were organized into affective, cognitive, and psychomotor domains and general readiness. This evaluation occurred at the beginning of the final practicum to assess student progress toward readiness for practice. Students scored highest in professional attributes but lowest in time management, prioritization, management of multiple patients, and pharmacology knowledge. Results can be used to inform teaching strategies, strengthen academic-clinical partnerships, and promote readiness for entry-level practice. PMID- 29794885 TI - Normative Values of Knee Extensor Isokinetic Strength for Older Women and Implications on Physical Function. AB - BACKGROUND AND PURPOSE: Lower-limb strength is required for everyday activities and thus its evaluation has been especially emphasized in older adults. Isokinetic testing is a criterion standard method to assess muscle strength; however, lack of reference values limits its usefulness in geriatric evaluation and rehabilitation. The aim of this study was to develop reference values of knee extensor isokinetic strength for older women. As a secondary aim, functional tests were performed for clinical significance validation. METHODS: A total of 453 older women aged 60 to 84 years participated in this study. Knee extensor isokinetic strength was measured using the Biodex System dynamometer at 60 degrees per second. The Timed Up and Go test and the 5 times Sit-to-Stand test were used for functional performance evaluation. Participants were categorized into age groups of 5 years range. The 20th, 40th, 60th, and 80th percentiles were used for stratification purposes. RESULTS AND DISCUSSION: As expected, mean strength values significantly decreased with advancing age groups. Isokinetic percentile groups are presented according to age. Individuals in the lower percentile strata showed significantly reduced performance in both the Timed Up and Go and 5 times Sit-to-Stand tests (P < .05). CONCLUSION: This study provides normative values of isokinetic knee extensor strength in older women. The association between lower isokinetic knee extensor strength strata and reduced functional capacity supports the potential application of these reference values in clinical and research settings. Future studies should ascertain these findings in different female populations. PMID- 29794886 TI - Relationship Between Body Mass Index and Static and Dynamic Balance in Active and Inactive Older Adults. AB - BACKGROUND AND PURPOSE: Although the association between higher body mass index and poorer balance has been observed in older adults, the role of physical activity in this relationship is not well established. This study aimed to provide scientific evidence about the relationship between body mass index and balance, taking into account the amount of physical activity performed as a confounding variable. METHODS: We collated cross-sectional data from 160 community-dwelling older adults whom we divided into 3 body mass index categories: normal weight (>=18.50-24.99 kg/m), overweight (25.00-29.99 kg/m), and obese (>=30.00-34.99 kg/m). We classified the participants as inactive or active by means of the Yale Physical Activity Questionnaire. We carried out static and dynamic balance measurements by means of a force platform and through the performance of the Timed Up and Go test, respectively. RESULTS: We found statistically significant correlations between static balance, dynamic balance, and body mass index in inactive normal (r = 0.280; P = .035; r = 0.300; P = .031) and inactive overweight (r = 0.395; P = .025; r = 0.339; P = .023) people. We observed moderately strong and fair significant correlations between static/dynamic balance and BMI in inactive (r = .603; P = .028; and r = 0.720; P = .020) and active (r = 0.406; P = .037; and r = 0.378; P = .037) obese people, respectively. CONCLUSION: We conclude that the amount of physical activity performed is a potential contributing factor affecting the association between body mass index and balance in older persons. These findings could be of importance when identifying the main factors that influence postural control among older adults with obesity. PMID- 29794887 TI - Development and Evaluation of an Educational Initiative to Improve Hospital Personnel Preparedness to Care for Children with Autism Spectrum Disorder. AB - OBJECTIVE: To evaluate the effectiveness of a multimodal educational curriculum on increasing hospital personnel's awareness of successful strategies and comfort in caring for children with autism spectrum disorder (ASD). METHODS: We developed a 3-part training for front-line staff (i.e., front desk, clinical assistants, and phlebotomists) in 8 outpatient hospital departments frequented by patients with ASD. Following a needs assessment, participants completed an online educational module and then attended an in-person seminar tailored to each department. To evaluate training effectiveness, we administered pre-, immediate post-, and 1 month post-training surveys assessing personnel attitudes, comfort, perceived knowledge, and behaviors around caring for patients with ASD. RESULTS: We trained 168 staff members from 8 departments. On the needs assessment, participants (N = 129) reported a mean 2.5 behavioral incidents involving patients with ASD over the previous 3 months; 92% believed that the training would be helpful for their work. Across pre-, immediate- and 1-month post training surveys, scores improved on all questions related to personnel attitudes about the importance of ASD-friendly care, comfort interacting with patients with ASD, perceived knowledge about ASD, and self-reported frequency of behaviors intended to help children with ASD adjust to the hospital setting (p < 0.05). There was no difference in baseline scores or change in scores between clinical and nonclinical personnel. On a program evaluation (N = 57), 81% rated the training as "very good" or "excellent," and 87% reported that they would be able to apply training material immediately to their role. CONCLUSION: This training initiative led to improvement in attitudes, comfort level, perceived knowledge, and self-reported behaviors of hospital personnel working with patients with ASD, which was maintained over 1 month. PMID- 29794888 TI - Risk and Protective Factors for Externalizing Behavior at 3 Years: Results from the All Our Families Pregnancy Cohort. AB - OBJECTIVE: This study examines risk and protective factors for externalizing behavior in children aged 3 years to inform early interventions and enhance school readiness. METHOD: A total of 1314 mothers participating in a longitudinal study completed questionnaires when their children turned 2 years and again at the age of 3 years. Externalizing behavior was assessed using a short version of the Child Behavior Checklist. Risk and protective factors included the child's characteristics, maternal mental health and disposition, socioeconomic status, and community engagement and child care. Logistic regression models produced crude and adjusted odds ratios (AORs). RESULTS: Poor maternal mental health and high levels of maternal neuroticism were associated with an increased risk for externalizing problems at 3 years (AOR, 1.66; 95% confidence interval [CI], 1.16 2.40 and AOR, 2.28; 95% CI, 1.58-3.30). Care by their mother, relative, or a nanny (compared with being in child care) also conferred an increased risk (AOR, 1.38; 95% CI, 1.01-1.90). Mothers' community engagement modified the risk for boys, such that boys whose mothers did not participate in community activities were 4 times more likely to have externalizing problems than did boys whose mothers engaged in community activities. CONCLUSION: Families in which mothers experience mental health challenges or have dispositional traits that increase the risk of externalizing behaviors can be identified early. Identification provides the opportunity to promote engagement with parenting supports to improve the outcomes of the child and family. Providing opportunities for children to practice their self-regulation skills through participation in child care and community activities promotes development and mitigates the risk of externalizing behavior. PMID- 29794889 TI - Supporting Development During Military Deployment and After April 2018. AB - CASE: Ryan is a 6-year-old child new to your primary care practice after relocating from out of state with his father and younger sister. Ryan's grandmother recently expressed concerns about Ryan's social skills and behavior. He was subsequently diagnosed by a developmental and behavioral pediatrician with autism spectrum disorder, global developmental delay, and attention deficit hyperactivity disorder. At your first visit with Ryan, his father provides the following history: When Ryan was 3 years old, he was living with his mother and infant sister while his father was serving his fourth tour of duty with the marines in Afghanistan. One night, while Ryan was sleeping in bed with his mother, she died suddenly from a pulmonary embolism. Ryan's father was then called home from Afghanistan to take care of the children.Ryan's father explains that this was his first time serving as a primary caregiver for any prolonged period. He felt overwhelmed and unprepared, both cognitively and emotionally, to return from a combat zone and assume full-time, single-parent responsibilities. Ryan's father admitted knowing little about child development and had not had sustained interactions with his own children because of frequent deployments. He did not appreciate the delays and atypicalities in Ryan's development until he moved back home with his own mother and she expressed concerns. Ryan's father had his own psychological, emotional, and physical challenges from participating in active combat, including chronic pain in his shoulder from multiple gunshot wounds. Despite moving back home to be close to his family, Ryan's father admits feeling isolated and reports that "no one knows what it feels like."How would you provide unique support to Ryan and his family? What treatment modalities are particularly important to emphasize? PMID- 29794890 TI - Influence of a Vented Mouthguard on Physiological Responses in Handball. AB - Schulze, A, Laessing, J, Kwast, S, and Busse, M. Influence of a vented mouthguard on physiological responses in handball. J Strength Cond Res XX(X): 000-000, 2018 Mouthguards (MGs) improve sports safety. However, airway obstruction and a resulting decrease in performance are theoretical disadvantages regarding their use. The study aim was to assess possible limitations of a "vented" MG on aerobic performance in handball. The physiological effects were investigated in 14 male professional players in a newly developed handball-specific course. The measured values were oxygen uptake, ventilation, heart rate, and lactate. Similar oxygen uptake (V[Combining Dot Above]O2) values were observed with and without MG use (51.9 +/- 6.4 L.min.kg vs. 52.1 +/- 10.9 L.min.kg). During maximum load, ventilation was markedly lower with the vented MG (153.1 +/- 25 L.min vs. 166.3 +/- 20.8 L.min). The endexpiratory concentrations of O2 (17.2 +/- 0.5% vs. 17.6 +/- 0.8%) and CO2 (4.0 +/- 0.5% vs. 3.7 +/- 0.6%) were significantly lower and higher, respectively, when using the MG. The inspiration and expiration times with and without the MG were 0.6 +/- 0.1 seconds vs. 0.6 +/- 0.1 seconds and 0.7 +/- 0.2 seconds vs. 0.6 +/- 0.2 seconds (all not significant), respectively, indicating that there was no relevant airflow restriction. The maximum load was not significantly affected by the MG. The lower ventilation for given V[Combining Dot Above]O2 values associated with MG use may be an effect of improved biomechanics and lower respiratory drive of the peripheral musculature. PMID- 29794891 TI - Global Training Effects of Trained and Untrained Muscles With Youth Can be Maintained During 4 Weeks of Detraining. AB - Chaouachi, A, Ben Othman, A, Makhlouf, I, Young, JD, Granacher, U, and Behm, DG. Global training effects of trained and untrained muscles with youth can be maintained during 4 weeks of detraining. J Strength Cond Res XX(X): 000-000, 2018 Global (whole-body) effects of resistance training (i.e., cross-education) may be pervasive with children. Detraining induces less substantial deficits with children than adults. It was the objective of this study to investigate the global responses to 4 weeks of detraining after 8 weeks of unilateral leg press (LP) training in 10-13-year-old, pre-peak-height-velocity stage boys. Subjects were randomly separated into 2 unilateral resistance training groups (high load/low repetitions [HL-LR] and low load/high repetitions [LL-HR], and control group). Assessments at pre-training, post-training, and detraining included dominant and nondominant limbs, unilateral, 1 repetition maximum (1RM) and 60% 1RM LP, knee extension, knee flexion, elbow flexion, and handgrip maximal voluntary isometric contraction (MVIC), and countermovement jump (CMJ). All measures significantly increased from pre-test to detraining for both training programs, except for elbow flexion MVIC with increases only with HL-LR. All measures except CMJ and handgrip MVIC significantly decreased from post-test to detraining, except for elbow flexion MVIC with decreases only with HL-LR. The dominant trained limb experienced significantly greater LP improvements (pre- to detraining) and decrements (post- to detraining) with LP 1RM and 60% 1RM LP. In conclusion, youth HL-LR and LL-HR global training effects of trained and untrained limbs demonstrate similar benefits (pre- to detraining) and decrements (post- to detraining) with detraining. The findings emphasize that training any muscle group in a child can have positive global implications for improved strength and power that can persist over baseline measures for at least a month. PMID- 29794893 TI - Hamstring-to-Quadriceps Torque Ratios of Professional Male Soccer Players: A Systematic Review. AB - Baroni, BM, Ruas, CV, Ribeiro-Alvares, JB, and Pinto, RS. Hamstring-to-quadriceps torque ratios of professional male soccer players: A systematic review. J Strength Cond Res XX(X): 000-000, 2018-The goal of this review was to determine the isokinetic hamstring-to-quadriceps (H/Q) torque ratios of professional male soccer players. Systematic searches were independently carried out by 2 researchers in 7 electronic databases. Only studies with teams from the first or second national leagues were included. From these studies, we extracted the players' H/Q conventional (concentric/concentric) and/or functional (eccentric/concentric) ratios. The initial search resulted in 2,128 articles that were filtered to 30 articles (1,727 players) meeting the inclusion criteria. The H/Q conventional ratio was assessed in 27 studies (1,274 players), whereas the H/Q functional ratio was assessed in 15 studies (1,082 players). The H/Q conventional ratio mean scores of professional male soccer players were close to 60% when tested at low to intermediate angular velocities (12 degrees .s = 52 +/- 7%; 30 degrees .s = 52 +/- 8%; 60 degrees .s = 65 +/- 12%; 90 degrees .s = 57 +/- 6%; 120 degrees .s = 65 +/- 16%; 180 degrees .s = 67 +/- 17%) and around 70-80% at fast angular velocities (240 degrees .s = 80 +/- 40%; 300 degrees .s = 70 +/- 15%; 360 degrees .s = 80 +/- 13%). The H/Q functional ratio mean scores of professional male soccer players were close to 80% at 60 degrees .s (79 +/- 19%), around 100-130% at intermediate to fast angular velocities (120 degrees .s = 127 +/- 42%; 180 degrees .s = 96 +/- 19%; 240 degrees .s = 109 +/- 22%; 300 degrees .s = 123 +/- 18%), and near or above 130% when angular testing velocities were mixed (eccentric hamstring < concentric quadriceps; 30/240 degrees .s = 132 +/- 26%; 60/180 degrees .s = 129 +/- 20%; 60/240 degrees .s = 153 +/- 30%). In conclusion, considering the tested isokinetic angular velocity, professional male soccer players do not meet the traditional reference landmarks used to assess the strength balance between quadriceps and hamstring muscles (i.e., 60 and 100% for H/Q conventional and functional ratios, respectively), which supports a need for specific reference values according to the angular velocity selected for testing H/Q torque ratios. PMID- 29794894 TI - Agreement Between Bioelectrical Impedance and Dual-Energy X-Ray Absorptiometry to Track Changes in Fat-Free Mass After Resistance Training in Older Women. AB - Nascimento, MA, Silva, DRP, Ribeiro, AS, Pina, FLC, Gerage, AM, Gobbo, LA, Mayhew, JL, and Cyrino, ES. Agreement between bioelectrical impedance and dual energy x-ray absorptiometry to track changes in fat-free mass after resistance training in older women. J Strength Cond Res XX(X): 000-000, 2018-The aim of our study was to compare the agreement between bioelectrical impedance (BIA) and dual energy X-ray absorptiometry (DXA) to track changes on fat-free mass (FFM) after a resistance training (RT) program in older women. Forty-three older women (65.2 +/ 4.6 years, 59.5 +/- 9.2 kg, 156.4 +/- 6.0 cm, 24.3 +/- 3.3 kg.m) participated in a RT intervention (12 weeks, 8 exercises, 2 sets, 10-15 repetitions, 3 nonconsecutive days per week). Fat-free mass changes were determined by a single frequency BIA device (EQ1), 6 BIA prediction equations for older women (EQ2, EQ3, EQ4, EQ5, EQ6, and EQ7), and DXA. At pretraining, 3 equations overpredicted, and 3 underpredicted DXA FFM (F = 244.63, p < 0.001), although all equations had high correlations with DXA (r = 0.78-0.83). After training, 4 equations overpredicted and one underpredicted DXA FFM (F = 176.25, p < 0.001). Dual-energy X-ray absorptiometry detected significant gains in FFM (0.65 +/- 0.82 kg; p < 0.05), as did EQ3 (0.55 +/- 1.69 kg; p < 0.05), and EQ4 (0.61 +/- 1.88 kg; p < 0.05), whereas the remaining equations did not indicate significant changes in FFM. Low correlations between FFM and equation change values suggest that single-frequency BIA-derived equations may not provide sufficient accuracy to track changes in FFM after 12 weeks of RT in older women. PMID- 29794896 TI - Not So Smart: Cell Phone Use Hurts Our Patients and Profession. AB - The clinical setting is no place for divided attention. PMID- 29794892 TI - Normative Quadriceps and Hamstring Muscle Strength Values for Female, Healthy, Elite Handball and Football Players. AB - Risberg, MA, Steffen, K, Nilstad, A, Myklebust, G, Kristianslund, E, Moltubakk, MM, and Krosshaug, T. Normative quadriceps and hamstring muscle strength values for female, healthy, elite handball and football players. J Strength Cond Res 32(8): 2314-2323, 2018-This study presents normative values for isokinetic knee extension and flexion muscle strength tests in 350 elite, female, handball (n = 150) and football (n = 200) players. Isokinetic concentric muscle strength tests at 60 degrees .sec were recorded bilaterally using a dynamometer. Peak torque (in Newton meter [N.m]), body mass normalized peak torque (N.m.kg), and hamstring to quadriceps ratio (H:Q ratio) for dominant and nondominant legs were recorded. The female elite players were 20.9 +/- 4.0 years, started playing at the elite level at the age of 18.2 +/- 2.7 years, with a mean of 9.7 +/- 2.2 hours of weekly in season training. Handball players demonstrated greater quadriceps muscle strength compared with football players (11.0%) (p < 0.001), also when normalized to body mass (4.1%) (p = 0.012), but not for weight-adjusted hamstring muscle strength. The H:Q ratio was higher on the dominant compared with the nondominant leg for handball players only (p = 0.012).The H:Q ratio was significantly lower for handball players (0.58) compared with football players (0.60) (p < 0.02). These normative values for isokinetic knee extension and flexion torques of healthy, elite, female handball and football players can be used to set rehabilitation goals for muscle strength after injury and enable comparison with uninjured legs. Significantly greater quadriceps muscle strength was found for handball players compared with football players, also when normalized to body mass. PMID- 29794895 TI - Nurses Wanted-Almost Everywhere. AB - It seems the nursing shortage has arrived. PMID- 29794897 TI - Nutrition and Wound Healing. PMID- 29794898 TI - Ostomy Care. PMID- 29794899 TI - Simulation Training. PMID- 29794900 TI - Recognizing Delirium. PMID- 29794901 TI - Relaxing Food Restrictions on Women in Labor. PMID- 29794902 TI - Colorado 'Alternative to Opioids' Pilot Project Exceeds Goals. AB - The ED pain management program reduced opioid use in populations at high risk for misuse or abuse. PMID- 29794904 TI - NewsCAP: Only 50% of teens with depression are diagnosed before they reach adulthood. PMID- 29794903 TI - How Media Influences Perceptions of Suicide. AB - A panel separates myths from facts. PMID- 29794905 TI - The Safety and Quality of Abortions in the United States. AB - A review documents few complications, but location matters. PMID- 29794906 TI - NewsCAP: All schools need a full-time nurse, preferably with a baccalaureate, says the AAN. PMID- 29794907 TI - NewsCAP: E-Cigarettes pose more harm than good as a tool to reduce smoking. PMID- 29794908 TI - Unsafe Firearm Storage in Homes with Children. AB - Only about one-third follow AAP safety guidelines. PMID- 29794909 TI - NewsCAP: Study finds increased infant mortality from unintentional suffocation. PMID- 29794910 TI - NewsCAP: APHA unlocks free public access to articles on firearm issues and research. PMID- 29794911 TI - Making Hospitals Less Threatening to Patients with Dementia. AB - Measures have been proposed, but how realistic are they? PMID- 29794912 TI - Trump Administration Opens Division of Conscience and Religious Freedom. AB - In controversial move, federal health department signals shift in civil rights focus. PMID- 29794915 TI - Cardiotocography vs. Intermittent Auscultation in Assessing Fetal Well-Being. AB - Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org. PMID- 29794917 TI - FDA to Minimize Abuse Potential of OTC Antidiarrheal. PMID- 29794916 TI - Antibiotic May Increase CV Risk in those with Heart Disease. PMID- 29794918 TI - FDA Approves First Treatment for Nonmetastatic, Castration-Resistant Prostate Cancer. PMID- 29794919 TI - Bladder Cancer Drug Approved to Treat Stage III Non-Small Cell Lung Cancer. PMID- 29794920 TI - Cavitation. PMID- 29794921 TI - 1 CE Test Hour: Original Research: Understanding the Hospital Experience of Older Adults with Hearing Impairment. PMID- 29794922 TI - 1.5 CE Test Hours: Understanding the Nurse's Role in Managing Gaucher Disease. PMID- 29794923 TI - The Benefits of Implementing an Early Mobility Protocol in Postoperative Neurosurgical Spine Patients. AB - : : Background: Despite the known benefits of early postsurgical mobility, there are no clear recommendations on early mobility among uncomplicated postoperative neurosurgical spine patients. PURPOSE: The purpose of this quality improvement initiative was to establish an NP-led early mobility protocol to reduce uncomplicated postsurgical spine patients' length of stay (LOS) in the hospital and eliminate the variability of postsurgical care. A secondary objective was to educate and empower nursing staff to initiate the early mobility protocol independently and incorporate it in their practice to improve patient care. METHODS: Two neurosurgery NPs led an interprofessional team to develop the early mobility protocol. Team members provided preadmission preoperative education to communicate the necessity for early mobility and provide information about the protocol. New nursing guidelines called for patient mobility on the day of surgery, within six hours of arrival on the medical-surgical unit. Nurses were empowered to get patients out of bed independently, without a physical therapy consultation; they also removed urinary catheters and discontinued IV opioids when patients' status permitted. RESULTS: Over a one-year period, implementation of the protocol resulted in a nine-hour reduction in LOS per hospitalization in neurosurgical spine patients who underwent lumbar laminectomies. The protocol also allowed nurses more autonomy in patient care and was a catalyst for patient involvement in their postoperative mobility. Given the success of the protocol, it is being replicated by other surgical services throughout the organization. CONCLUSIONS: This low-cost, high-reward initiative aligns with the strategic plan of the organization and ensures that high-quality, patient-centered care remains the priority. NPs in other institutions can modify this protocol to promote postoperative mobility in their organizations. PMID- 29794924 TI - The Hard of Hearing Patient. AB - Editor's note: From its first issue in 1900 through to the present day, AJN has unparalleled archives detailing nurses' work and lives over more than a century. These articles not only chronicle nursing's growth as a profession within the context of the events of the day, but they also reveal prevailing societal attitudes about women, health care, and human rights. Today's nursing school curricula rarely include nursing's history, but it's a history worth knowing. To this end, From the AJN Archives highlights articles selected to fit today's topics and times.This February 1944 article is by Louise Neuschutz, who wrote extensively in AJN and elsewhere about the hard of hearing, deafness, and lipreading. Here she discusses the ways in which nurses can help "war-deafened men... returning steadily from the various fronts." Her guidance is critically relevant more than 70 years later, and we would do well today to follow her practical tips for communicating with the hearing impaired.A hearing deficit can magnify the stresses of hospitalization and even affect patient outcomes. In this issue, Amy Funk and colleagues explore the potential hearing-related problems of hospitalized patients in their qualitative study, "Understanding the Hospital Experience of Older Adults with Hearing Impairment." PMID- 29794925 TI - Getting and Giving Report. AB - : This column is designed to help new nurses in their first year at the bedside-a time of insecurity, growth, and constant challenges-and to offer advice as they learn what it means to be a nurse. This article offers strategies new nurses can use and specific steps they can take to help them succeed in both giving and receiving report. PMID- 29794926 TI - When Disaster Strikes. AB - Apps, websites, and volunteer organizations can provide assistance. PMID- 29794927 TI - Caring with Intention: Hospice Care and the Human Family. AB - : Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely-and often more personal perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com. PMID- 29794928 TI - Legal Issues in Dismissing Unvaccinated Patients. AB - : Even small proportions of parents refusing vaccines have important consequences. PMID- 29794929 TI - An Unflinching Exploration of Trauma and Obesity. AB - : Roxane Gay's Hunger and why it matters for nurses. PMID- 29794930 TI - Aromatherapy Relieves Nausea in ED Patients. PMID- 29794931 TI - Effect of Body Positioning in Critically Ill Patients. PMID- 29794932 TI - Determining Differences Between Physician And Nursing Care. PMID- 29794933 TI - Patient Coaching Saves Lives And Money. PMID- 29794934 TI - Probiotics in the Clinical Management of Lower GI Symptoms. PMID- 29794935 TI - The Thin Flat Line Between Life and Death. AB - In nursing, there's often a delicate balance between worlds. PMID- 29794936 TI - Predictive Performance of Postoperative Neutrophil Gelatinase-Associated Lipocalin for Development of Chronic Kidney Disease After Liver Transplantation. PMID- 29794937 TI - Local Injections of Tacrolimus-loaded Hydrogel Reduce Systemic Immunosuppression related Toxicity in Vascularized Composite Allotransplantation. AB - BACKGROUND: Routine application of vascularized composite allotransplantation is hampered by immunosuppression-related health comorbidities. To mitigate these, we developed an inflammation-responsive hydrogel for local immunosuppression. Here, we report on its long-term effect on graft survival, immunological, and toxicological impact. METHODS: Brown Norway-to-Lewis rat hindlimb transplantations were treated either systemically with daily injections of 1 mg/kg tacrolimus (TAC) or with subcutaneous intragraft injections of hydrogel containing 7 mg TAC, every 70 days. Animals were monitored for rejection or other pathology for 280 days. Systemic and graft TAC levels, regulatory T cells, and donor cell chimerism were measured periodically. At endpoint, markers for kidney, liver, and metabolic state were compared to naive age-matched rats. RESULTS: Both daily systemic TAC and subcutaneous intragraft TAC hydrogel at 70-day intervals were able to sustain graft survival longer than 280 days in 5 of 6 recipients. In the hydrogel group, 1 graft progressed to grade 3 rejection at postoperative day 149. In systemic TAC group, 1 animal was euthanized due to lymphoma on postoperative day 275. Hydrogel treatment provided stable graft and reduced systemic TAC levels, and a 4 times smaller total TAC dose compared with systemic immunosuppression. Hydrogel-treated animals showed preserved kidney function, absence of malignancies or opportunistic infections and increased hematopoietic chimerism compared with systemic immunosuppression. CONCLUSIONS: Our findings demonstrate that localized immunosuppression with TAC hydrogel is a long-term safe and reliable treatment. It may reduce the burden of systemic immunosuppression in vascularized composite allotransplantation, potentially boosting the clinical application of this surgical intervention. PMID- 29794938 TI - Engineering Confined and Prevascularized Sites for Islet Transplantation. PMID- 29794939 TI - The role of nursing with the journal Menopause and NAMS over the last 25 years: contributions and collaboration. PMID- 29794940 TI - The North American Menopause Society (NAMS) Continuing Medical Education Activity. PMID- 29794941 TI - NAMS CME activity self-assessment examination. PMID- 29794942 TI - Major Laparoscopic Intraperitoneal Surgery Performed With Combined Bilateral Subcostal Transversus Abdominal Plane Block and Celiac Plexus Block, Intravenous Sedation Without Tracheal Intubation: A Feasibility Study of 3 Cases. AB - OBJECTIVES: Major abdominal surgery usually requires general anesthesia with tracheal intubation and may be supplemented with neuraxial anesthesia to provide intraoperative and postoperative pain relief. Attempts at using only neuraxial anesthesia for major abdominal surgery have often been shown to be poorly effective. This report demonstrates that laparoscopic colonic surgical procedures can be performed with ultrasound-guided blocks (bilateral transversus abdominal plane block and celiac plexus block) and intravenous sedation, while avoiding general or neuraxial anesthesia. CASE REPORT: We report our preliminary experience in 3 patients (all American Society of Anesthesiologists physical status III) who underwent laparoscopic colonic surgery without general anesthesia. Intraoperative visceral analgesia was provided by single-injection ultrasound anterior celiac plexus block to which was added a bilateral subcostal transversus abdominal plane block to obtain parietal analgesia. Light intravenous sedation was added. Surgical exposure was satisfactory, and no patient complained of any symptom during the procedure. No adverse effect was recorded. Postoperative pain was minimal, and recovery was enhanced with mobilization and walking within hours after surgery. Patient satisfaction was excellent. CONCLUSIONS: To date, celiac plexus block has been used almost exclusively to relieve pancreatic cancer pain. This is the first report in which it is shown that major intra-abdominal surgery can be performed almost exclusively with regional anesthesia while avoiding adverse effects and problems associated with either general or neuraxial anesthesia. In addition, prolonged postoperative pain relief facilitated early recovery. PMID- 29794943 TI - Erector Spinae Plane Block Versus Retrolaminar Block: A Magnetic Resonance Imaging and Anatomical Study. AB - BACKGROUND AND OBJECTIVES: The erector spinae plane (ESP) and retrolaminar blocks are ultrasound-guided techniques for thoracoabdominal wall analgesia involving injection into the musculofascial plane between the paraspinal back muscles and underlying thoracic vertebrae. The ESP block targets the tips of the transverse processes, whereas the retrolaminar block targets the laminae. We investigated if there were differences in injectate spread between the 2 techniques that would have implications for their clinical effect. METHODS: The blocks were performed in 3 fresh cadavers. The ESP and retrolaminar blocks were performed on opposite sides of each cadaver at the T5 vertebral level. Twenty milliliters of a radiocontrast dye mixture was injected in each block, and injectate spread was assessed by magnetic resonance imaging and anatomical dissection. RESULTS: Both blocks exhibited spread to the epidural and neural foraminal spaces over 2 to 5 levels. The ESP block produced additional spread to intercostal spaces over 5 to 9 levels and was associated with a greater extent of craniocaudal spread along the paraspinal muscles. CONCLUSIONS: The clinical effect of ESP and retrolaminar blocks can be explained by epidural and neural foraminal spread of local anesthetic. The ESP block produces additional intercostal spread, which may contribute to more extensive analgesia. The implications of these cadaveric observations require confirmation in clinical studies. PMID- 29794944 TI - Use of Serratus Plane Block for Repair of Coarctation of Aorta: A Report of 3 Cases. AB - OBJECTIVES: The practice of regional anesthesia techniques (thoracic, epidural, paravertebral) in pediatric cardiac surgery enhances perioperative outcomes such as improved perioperative analgesia, decreased stress response, early extubation, and shortened hospital stay. However, these blocks can be technically challenging and can be associated with unacceptable failure rate and complications in infants. For these reasons, regional anesthesia is sometimes avoided in pediatric cardiac surgery. We describe the simple and effective serratus plane block for thoracotomy analgesia in 2 neonates and a child. CASE REPORT: We present 3 pediatric patients, each of whom was having coarctation repair and received an ultrasound-guided serratus plane block for thoracotomy analgesia. The patients were 3 days, 14 days, and 4 years old, weighing from 1.9 to 16 kg. The serratus plane block was performed prior to surgical incision. The block was technically simple compared with thoracic epidural or paravertebral block. All patients were extubated immediately after completion of surgery. Apart from the induction dose of fentanyl (2 MUg/kg), no further opioids were required intraoperatively. Postoperative opioid requirements as well as duration of intensive care and hospital stay were lower than recent averages (for the same demographic and procedure) in our hospital. CONCLUSIONS: We propose that the serratus plane block is a simple procedure that provides good perioperative analgesia for infant thoracotomy, potentially facilitating early extubation and a shorter hospital stay. PMID- 29794946 TI - Semen Quality in Chinese College Students: Associations With Depression and Physical Activity in a Cross-Sectional Study. AB - OBJECTIVE: Behavioral and psychosocial factors have been associated with a decline of the quality of semen. However, the relationship of depression and physical activity (PA) with semen quality remains unclear. METHODS: Data were obtained from 587 young male Chinese college students in June 2013. Participants completed a questionnaire assessing life-style factors, the Zung self-rated depression scale, and three items related to PA. They underwent a physical examination and provided a semen sample and a blood sample for reproductive hormones (testosterone, estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and prolactin). RESULTS: Men with high depression scores (n = 63, 10.7%) had lower sperm concentration (M (SD) = 66.9 (74.5) versus 72.6 (56.9) [10/ml], p = .043) and total sperm count (M (SD) = 241.6 (299.7) versus 257.0 (204.0) [10], p = .024) than nondepressed men. Participants with low PA levels (n = 99, 16.9%) had lower total sperm count (M (SD) = 204.4 (153.7) versus 265.8 (225.8) [10/ml], p = .017) than participants with higher activity levels. After adjusting for potential confounders, depressed men had 18.90% (95% confidence interval [CI] = 1.14%-33.47%) lower sperm concentration and 21.84% (95% CI = 3.39%-36.90%) lower total sperm count than nondepressed men. Men with low PA levels had 23.03% (95% CI = 2.80%-46.89%) lower total sperm count than physically active participants. An interaction effect between depression and PA on sperm concentration was detected (p = .033). There were no significant associations of depression and PA with reproductive hormones (p > .05). CONCLUSIONS: Depression and low levels of PA are associated with lower levels of semen quality, which may have implications for reproductive health. PMID- 29794947 TI - Myocardial stunning-induced left ventricular dyssynchrony on gated single-photon emission computed tomography myocardial perfusion imaging. AB - OBJECTIVES: Myocardial stunning provides additional nonperfusion markers of coronary artery disease (CAD), especially for severe multivessel CAD. The purpose of this study is to assess the influence of myocardial stunning to the changes of left ventricular mechanical dyssynchrony (LVMD) parameters between stress and rest gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). PATIENTS AND METHODS: A total of 113 consecutive patients (88 males and 25 females) who had undergone both stress and rest Tc sestamibi gated SPECT MPI were retrospectively enrolled. Suspected or known patients with CAD were included if they had exercise stress MPI and moderate to severe myocardial ischemia. Segmental scores were summed for the three main coronary arteries according to standard myocardial perfusion territories, and then regional perfusion, wall motion, and wall thickening scores were measured. Myocardial stunning was defined as both ischemia and wall dysfunction within the same coronary artery territory. Patients were divided into the stunning group (n=58) and nonstunning group (n=55). RESULTS: There was no significant difference of LVMD parameters between stress and rest in the nonstunning group. In the stunning group, phase SD and phase histogram bandwidth of contraction were significantly larger during stress than during rest (15.05+/-10.70 vs. 13.23+/ 9.01 and 46.07+/-34.29 vs. 41.02+/-32.16, P<0.05). Phase SD and phase histogram bandwidth of relaxation were also significantly larger during stress than during rest (21.21+/-13.91 vs. 17.46+/-10.52 and 59.03+/-37.82 vs. 52.38+/-36.89, P<0.05). CONCLUSION: Both systolic and diastolic LVMD parameters deteriorate with myocardial stunning. This kind of change may have incremental values to diagnose CAD. PMID- 29794948 TI - Improved Peritoneal Cavity and Abdominal Organ Imaging Using a Biphasic Contrast Agent Protocol and Spectral Photon Counting Computed Tomography K-Edge Imaging. AB - OBJECTIVES: To validate in vitro the capability of a high-spatial-resolution prototype spectral photon-counting computed tomography (SPCCT) scanner to differentiate between 2 contrast agents and to assess in vivo the image quality and the feasibility to image the peritoneal cavity in rats using the 2 contrast agents simultaneously within the vascular and peritoneal compartments. MATERIALS AND METHODS: The authors performed SPCCT imaging (100 mAs, 120 kVp) with energy bin thresholds set to 30, 51, 64, 72, and 85 keV in vitro on a custom-made polyoxymethylene cylindrical phantom consisting of tubes with dilutions of both contrast agents and in vivo on 2 groups of adult rats using 2 injection protocols. Approval from the institutional animal ethics committee was obtained. One group received macrocylic gadolinium chelate intraperitoneal (IP) and iodine intravenous (IV) injections (protocol A, n = 3), whereas the second group received iodine IP and gadolinium IV (protocol B, n = 3). Helical scans were performed 35 minutes after IP injection and 20 seconds after IV injection. The SPCCT and contrast material images, that is, iodine and gadolinium maps, were reconstructed with a field of view of 160 mm, an isotropic voxel size of 250 MUm, and a matrix size of 640 * 640 pixels using a soft reconstruction kernel. The SPCCT images were reconstructed with 2 different spatial resolutions to compare the image quality (sharpness, diagnostic quality, and organ visualization) of SPCCT (250 MUm) with single-energy computed tomography (CT) (600 MUm). Two radiologists evaluated the peritoneal opacification index in 13 regions (score = 0-3 per region) on each type of image. Concentrations of contrast agents were measured in the organs of interest. RESULTS: In vitro, the concentration measurements correlated well with the expected concentrations. The linear regressions both had R values of 0.99, slopes of 0.84 and 0.87, and offsets at 0.52 and -0.38 mg/mL for iodine and gadolinium, respectively. In vivo, the SPCCT images were of better diagnostic quality, with increased sharpness compared with the CT-like images (P < 0.0001). Intraperitoneal diffusion was excellent, with similar peritoneal opacification index on SPCCT images and overlay of contrast material maps (P = 1) without a significant difference between protocol A (37.0 +/- 1.7) and protocol B (35.3 +/- 1.5) (P = 0.34). Only the contrast material maps demonstrated clear visual separation of the contrast agents, allowing specific quantification of the physiological enhancement in the liver, spleen, and kidney and the urinary clearance in the renal pelvis and bladder. Renal excretion of the contrast agents injected IP was observed and was consistent with blood diffusion. CONCLUSIONS: Spectral photon-counting CT can be used to perform a complete peritoneal dual-contrast protocol, enabling a good assessment of the peritoneal cavity and abdominal organs in rats. PMID- 29794945 TI - Brain Correlates of Mental Stress-Induced Myocardial Ischemia. AB - OBJECTIVE: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed on the role of behavioral factors such as emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula, and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD. METHODS: CAD patients (N = 170) underwent cardiac imaging with [Tc-99m] sestamibi single-photon emission tomography at rest and during a public speaking mental stress task. On another day, they underwent imaging of the brain with [O 15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions. RESULTS: Patients with mental stress induced myocardial ischemia showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p < .005). This was seen with both arithmetic stress and public speaking stress. Arithmetic stress was additionally associated with left insula activation, and public speaking with right pre/postcentral gyrus and middle temporal gyrus activation (p < .005). CONCLUSIONS: These findings suggest that mental stress-induced myocardial ischemia is associated with activation in brain areas involved in the stress response and autonomic regulation of the cardiovascular system. Altered brain reactivity to stress could possibly represent a mechanism through which stress leads to increased risk of CAD-related morbidity and mortality. PMID- 29794949 TI - Photon Counting Computed Tomography With Dedicated Sharp Convolution Kernels: Tapping the Potential of a New Technology for Stent Imaging. AB - OBJECTIVES: The aims of this study were to assess the value of a dedicated sharp convolution kernel for photon counting detector (PCD) computed tomography (CT) for coronary stent imaging and to evaluate to which extent iterative reconstructions can compensate for potential increases in image noise. MATERIALS AND METHODS: For this in vitro study, a phantom simulating coronary artery stenting was prepared. Eighteen different coronary stents were expanded in plastic tubes of 3 mm diameter. Tubes were filled with diluted contrast agent, sealed, and immersed in oil calibrated to an attenuation of -100 HU simulating epicardial fat. The phantom was scanned in a modified second generation 128-slice dual-source CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Erlangen, Germany) equipped with both a conventional energy integrating detector and PCD. Image data were acquired using the PCD part of the scanner with 48 * 0.25 mm slices, a tube voltage of 100 kVp, and tube current-time product of 100 mAs. Images were reconstructed using a conventional convolution kernel for stent imaging with filtered back-projection (B46) and with sinogram-affirmed iterative reconstruction (SAFIRE) at level 3 (I463). For comparison, a dedicated sharp convolution kernel with filtered back-projection (D70) and SAFIRE level 3 (Q703) and level 5 (Q705) was used. The D70 and Q70 kernels were specifically designed for coronary stent imaging with PCD CT by optimizing the image modulation transfer function and the separation of contrast edges. Two independent, blinded readers evaluated subjective image quality (Likert scale 0-3, where 3 = excellent), in-stent diameter difference, in-stent attenuation difference, mathematically defined image sharpness, and noise of each reconstruction. Interreader reliability was calculated using Goodman and Kruskal's gamma and intraclass correlation coefficients (ICCs). Differences in image quality were evaluated using a Wilcoxon signed-rank test. Differences in in-stent diameter difference, in-stent attenuation difference, image sharpness, and image noise were tested using a paired-sample t test corrected for multiple comparisons. RESULTS: Interreader and intrareader reliability were excellent (gamma = 0.953, ICCs = 0.891-0.999, and gamma = 0.996, ICCs = 0.918-0.999, respectively). Reconstructions using the dedicated sharp convolution kernel yielded significantly better results regarding image quality (B46: 0.4 +/- 0.5 vs D70: 2.9 +/- 0.3; P < 0.001), in-stent diameter difference (1.5 +/- 0.3 vs 1.0 +/- 0.3 mm; P < 0.001), and image sharpness (728 +/- 246 vs 2069 +/- 411 CT numbers/voxel; P < 0.001). Regarding in-stent attenuation difference, no significant difference was observed between the 2 kernels (151 +/- 76 vs 158 +/- 92 CT numbers; P = 0.627). Noise was significantly higher in all sharp convolution kernel images but was reduced by 41% and 59% by applying SAFIRE levels 3 and 5, respectively (B46: 16 +/- 1, D70: 111 +/- 3, Q703: 65 +/- 2, Q705: 46 +/- 2 CT numbers; P < 0.001 for all comparisons). CONCLUSIONS: A dedicated sharp convolution kernel for PCD CT imaging of coronary stents yields superior qualitative and quantitative image characteristics compared with conventional reconstruction kernels. Resulting higher noise levels in sharp kernel PCD imaging can be partially compensated with iterative image reconstruction techniques. PMID- 29794951 TI - Efficacy of Veinlite PEDI in Pediatric Peripheral Intravenous Access: A Randomized Controlled Trial. AB - : A previous study by Katsogridakis et al (Pediatr Emerg Care. 2008;24:83-88) evaluated the use of the white light Veinite transillumination device to improve vein access in children. Since then, advanced light emitting diode color lighting has been developed to improve the visualization of veins. To evaluate the efficacy of the new technology, we carried out a study in our pediatric emergency departments using the light emitting diode-based Veinlite PEDI (TransLite, Sugar Land, Tex). METHODS: A total of 112 pediatric patients were enrolled in the study. Children who presented to the emergency department aged 1 to 10 years old were randomly assigned to the Veinlite PEDI (Veinlite) group or standard of care (SoC) group. The primary outcome measure was first attempt success. Secondary outcome measures were number of intravenous (IV) attempts and time to peripheral intravenous catheter (PIC) placement. RESULTS: A total of 110 patients completed the study: 58 boys and 52 girls. The first attempt success rate was significantly higher in the Veinlite group compared with the SoC group (92.9% vs 72.2%, P < 0.004). In addition, the Veinlite group had a fewer number of attempts compared with the SoC group (1.07 +/- 0.54 vs 1.31 +/- 0.25, P = 0.04). The Veinlite group resulted in a shorter total time of attempts per patient compared with the SoC group (49.98 +/- 18.4 vs 59.68 +/- 22.5 P = 0.01). CONCLUSIONS: The use of new technology in the Veinlite PEDI (TransLite, Sugar Land, Tex), to assist with peripheral IV access in children, improves the first time success rate for IV access. Improved visualization of veins also reduced the number of attempts and the time required for PIC placement. These results suggest that the new technology of the Veinlite results in better PIC access than Veinlite transilluminaton device with white light. PMID- 29794950 TI - Adolescent Seizure in the Emergency Department Due to Concomitant Brugada Syndrome. AB - Brugada syndrome is an increasingly discussed entity in the emergency medicine and cardiology literature. However, there are few cases reported in the pediatric population. Seizure is a presentation common to pediatric emergency departments. This case report describes the clinical course, workup, and differential diagnosis of a 15-year-old male adolescent with first-time seizure and Brugada pattern on electrocardiogram. A brief review of the literature follows the case presentation. PMID- 29794952 TI - Puss Caterpillar Envenomation: Erucism Mimicking Appendicitis in a Young Child. AB - A 4-year-old female presented to the emergency department with 2 days of abdominal pain, nausea, and vomiting. She was tachycardic and had abdominal tenderness. Laboratory studies revealed a leukocytosis, hypokalemia, and metabolic acidosis. Her Pediatric Appendicitis Score (MDCalc) was calculated as 6, indicating that appendicitis could not be excluded. She was transferred to our pediatric hospital for further evaluation. Her ultrasound at our facility was normal. Upon reexamination, the patient was noted to have a red mark on her left index finger, and the family reported that the patient may have been stung by a puss caterpillar before the onset of her symptoms. The patient was treated with ondansetron, morphine, and intravenous fluids, and her symptoms resolved. Erucism frequently develops after stings from the puss caterpillar, which can be found through the southern United States. The most consistent clinical feature is pain. Numbness, muscle cramping, paresthesias, nausea, vomiting, and chest pain have also been described. Severe abdominal pain is reported rarely and may be mistaken for peritonitis. Analgesia is the mainstay of treatment. Topical icepacks have demonstrated inconsistent benefit in relieving pain. Oral medications, including acetaminophen, nonsteroidal anti-inflammatory drugs, and, rarely, opioids, typically suffice. Severe envenomations may require parenteral narcotics. PMID- 29794953 TI - Initial Characteristics and Clinical Severity of Hemophagocytic Lymphohistiocytosis in Pediatric Patients Admitted in the Emergency Department. AB - OBJECTIVES: The diagnosis and management of children with hemophagocytic lymphohistiocytosis (HLH) admitted in the emergency department (ED) are challenging. The present study aimed at describing the initial characteristics of pediatric patients with HLH upon admission in the ED. Moreover, the clinical severity of the condition was assessed. METHODS: We performed a retrospective study of patients who visited the pediatric ED and were newly diagnosed with HLH during hospitalization between February 2012 and January 2017. The patients were classified in the clinically unstable group if at least 1 of the following conditions was observed upon admission in the ED: hypoxia requiring oxygen supplementation, hypotension requiring inotropic support, coagulopathy with prothrombin time (international normalized ratio, >=1.5), and seizures or altered consciousness. RESULTS: We enrolled 31 pediatric patients with HLH, with a median age of 6.53 years (interquartile range, 1.35-13.24 years). Abdominal discomfort along with fever (74.2%) was the most common presenting symptom in patients admitted in the ED. Based on the HLH-2004 diagnostic criteria, fever (96.8%), hyperferritinemia (96.8%), splenomegaly (74.2%), hypertriglyceridemia and/or hypofibrinogenemia (67.7%), and bicytopenia (41.9%) were observed in the patients. However, only 8 patients (25.8%) met the criteria. Nineteen patients (61.3%) were included in the clinically unstable group. This group had lower albumin (2.3 vs 3.3 g/dL, P = 0.002) and fibrinogen levels and higher ferritin level and neutrophil count than the clinically stable group. Meanwhile, the number of clinical findings that met the diagnostic criteria was not different between the 2 groups. Lower albumin level was a significant risk factor in the clinically unstable group (odds ratio, 0.040; P = 0.004). CONCLUSIONS: Pediatric patients with HLH often have clinically unstable conditions upon admission in the ED. However, only few patients meet the HLH-2004 diagnostic criteria. Lower albumin level may be useful in assessing clinically unstable patients and preparing for possible deterioration. PMID- 29794954 TI - Adolescent With Spontaneous Splenic Rupture as a Cause of Hemoperitoneum in the Emergency Department: Case Report and Literature Review. AB - Spontaneous rupture of the spleen is a rare clinical condition that usually presents as a complication of a background pathology and can become a life threatening condition if it is not diagnosed in time. We present the case of a 15 year-old girl with abdominal pain and clinical data of hypovolemic shock. The simple tomographic study revealed deformation of the splenic architecture and hemoperitoneum. Surgery demonstrated splenic rupture with ptosis spleen and intraperitoneal free blood. The anatomopathological examination showed the presence of splenomegaly and findings suggestive of peliosis. It also highlights the known causes related to spontaneous splenic rupture. PMID- 29794955 TI - Early Functional Treatment of Proximal Phalanx Fractures in Children: A Case Series Study. AB - OBJECTIVES: The objective of this study was to assess proper indications a nonsurgical treatment regime for pediatric fractures of the proximal phalanx based on principles of early functional treatment. METHODS: A case series (evidence level 4) of 30 pediatric patients with fractures of the proximal phalanx were treated nonsurgically using protective dynamic splinting techniques and fiberglass casting material. Assessments were performed clinically and by x ray within 4 to 8 weeks of commencement of treatment. Outcome measures included Disabilities of the Arm, Shoulder, and Hand score questionnaire as well as fingertip palm distance (cm) and dynamic pain interval assessments. RESULTS: All fractures healed without any clinically apparent bony deformities. Disabilities of the Arm, Shoulder, and Hand scores were of 25.17 +/- 5.29 (mean +/- SD), which indicated good functional results usually within 2 weeks of removal of dynamic splints. Fingertip palm distance measurements at endpoints were of 0.17 +/- 0.27 cm (mean +/- SD), which indicated an almost free range of finger motion. Absence of pain perception under active finger motion (dynamic pain interval) was noted at 14.10 +/- 6.79 days (mean +/- SD). CONCLUSIONS: Well-established criteria for surgical treatment of phalangeal fractures exist. However, in our experience, a majority of pediatric fractures of the proximal phalanx can be safely treated nonsurgically with dynamic splinting along with shorter intervals of immobilization of the affected fingers and faster restoration of overall hand function compared to surgical treatment. PMID- 29794956 TI - Fitz-Hugh-Curtis Syndrome in Adolescent Females: A Diagnostic Dilemma. AB - Fitz-Hugh-Curtis syndrome is an extrapelvic manifestation of sexually transmitted infections. Partly because of the lack of specific clinical and laboratory features, this diagnosis is often missed or delayed. We describe a series of cases of patients with Fitz-Hugh-Curtis syndrome, where the diagnosis was initially not recognized and patients underwent extensive evaluations for their symptoms. Based on our experience, we also describe shared historical and physical features that may be useful in enhancing the recognition of patients with this disease. PMID- 29794957 TI - Quantification of Pain and Distress Associated With Intranasal Midazolam Administration in Children and Evaluation of Validity of Four Observational Measures. AB - OBJECTIVES: The aims of this study were to quantify the pain and distress associated with the administration of intranasal (IN) midazolam in young children using 4 observational measures and to evaluate the degree of validity of these measures. METHODS: We conducted a prospective observational pilot study. Children aged 1 to 7 years requiring IN midazolam were enrolled. Children were videotaped, and scores were assigned to baseline and administration phases using the Observational Scale of Behavioral Distress-Revised (OSBD-R), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), and the Faces-Legs-Activity-Cry Consolability (FLACC) scale. The cry duration following administration was assessed. Interrater reliability and convergent validity were determined for all 4 measures. Internal consistency and responsivity for the OSBD-R, CHEOPS, and FLACC scales were determined. RESULTS: We enrolled 20 children. The mean OSBD-R, CHEOPS, and FLACC scores associated with administration of IN midazolam were 27.1 (SD, 13.5), 11.5 (SD, 1.2), and 8.9 (SD, 2.7), respectively. The mean cry duration was 105.5 (SD, 68.8) seconds. The intraclass correlation coefficients for all measures ranged from 0.82 to 0.99. The Cronbach alpha's for the OSBD-R, CHEOPS, and FLACC were between 0.71 and 0.97. Pearson correlation coefficients for comparisons between OSBD-R, CHEOPS, and FLACC were between 0.82 and 0.96 but were between 0.32 and 0.51 for comparisons involving cry duration. CONCLUSIONS: We have identified estimates of pain and distress associated with administration of IN midazolam in young children that can be used to determine desired effect sizes for trials that study interventions to treat this pain and distress. The OSBD-R, CHEOPS, and FLACC scales are suitable choices for outcome measures. PMID- 29794958 TI - Herpes Simplex Virus Pneumonia in an Immunocompetent Child on Corticosteroids for Acute Wheezing. AB - Herpes simplex virus (HSV) is rarely the cause of pneumonia in immunocompetent patients. We describe a previously healthy child, with no evidence of an immunodeficiency, who presented to the emergency department with severe pneumonia, wheezing, and pleural effusions with a history of orolabial HSV infection. On admission, he was started on antibiotics and systemic corticosteroids but continued to deteriorate. Oral lesions, blood, and pleural fluid tested positive for HSV, and improvement was achieved only after the addition of acyclovir and discontinuation of steroids. We suggest that steroids should be used with caution in patients presenting with lower respiratory tract symptoms and herpetic oral lesions. PMID- 29794959 TI - Resident Performance of the Rapid Cardiopulmonary Assessment in the Emergency Department. AB - OBJECTIVES: The rapid cardiopulmonary assessment (RCPA) is an essential first step in effective resuscitation of critically ill children. Pediatric residents may not be achieving competency with resuscitative skills, including RCPA. Our objective was to determine how often pediatric residents complete the RCPA for actual patients. METHODS: This was an observational, cross-sectional study of senior residents (>=postgraduate year 2) performing the RCPA in the resuscitation area of a high-volume pediatric emergency department (PED), where pediatric residents are expected to perform the bedside examination and assessment for all medical (nontrauma) patients. Data were collected primarily by video review on a standard form. The primary outcome was completion of the RCPA, defined as both examination and verbalized assessment of the airway, breathing, and circulation. We explored the association between RCPA completion and both residency year and number of previous PED rotations. RESULTS: Complete data were collected from one randomly selected patient for 71 (95%) of 75 of eligible senior residents who rotated in the PED between January and June 2013. Two residents (3%) performed a complete RCPA. Verbalized assessment of circulation was especially rare (7/71; 10%). There was no association between RCPA completion and year of training or previous PED experience (P > 0.05). CONCLUSIONS: Senior pediatric resident performance of the RCPA in the resuscitation area of a high-volume PED was poor. There was no association between RCPA completion and greater resident experience, including in the PED. These findings add to a growing body of literature suggesting that pediatric residents are not achieving competency with the RCPA and resuscitation skills. PMID- 29794960 TI - An Unusual Pediatric Case of Seronegative Systemic Lupus Erythematosus Presented With Acute Abdominal Pain and Gross Hematuria. AB - A child with acute abdomen with gross hematuria occasionally visits the emergency department (ED). Usually, such a condition is subject to differential diagnosis for stones, injuries, or sometimes malignancies in the urinary tract. Here we introduce an unusual case of a 9-year-old girl who presented to ED with acute lower abdominal pain and gross hematuria. She had no medical history. An urgent computed tomographic image revealed a renal vein thrombosis. Laboratory tests for autoimmune diseases and coagulaopathies were performed, and the results were within normal ranges. At the time, she did not fulfil the criteria for systemic lupus erythematosus or antiphospholipid syndrome. Later at follow-up, however, she had a recurrent episode of renal vein thrombosis. A kidney biopsy was performed to reveal histology of membranous lupus nephropathy. The case emphasizes the importance for both ED physicians and pediatricians to have a clinical suspicion of autoimmune diseases in cases with major vessel thrombosis, even when the patient is seronegative. PMID- 29794961 TI - Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature. AB - Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC. PMID- 29794964 TI - Internal shoulder impingement in overhead athletes: an ultrasound imaging proposal. PMID- 29794963 TI - Musculoskeletal ultrasound: athletic injuries of the lower extremity. AB - Athletic injuries of the lower extremities are commonly encountered in clinical practice. While some pathology can be diagnosed on physical exam, others are a clinical dilemma with nonspecific symptomatology. In these situations, ultrasound imaging can be utilized as an exceptional diagnostic tool, offering unique advantages over other imaging modalities. This article will review the imaging characteristics of commonly encountered athletic injuries of the lower extremity. PMID- 29794962 TI - Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer. AB - Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis. PMID- 29794965 TI - Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development. AB - Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1), this toxin is metabolized and Aflatoxin M1 (AFM1) is excreted in milk. International Agency for Research on Cancer (IARC) classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation. PMID- 29794966 TI - Dietary Cholesterol Intake Is Not Associated with Risk of Type 2 Diabetes in the Framingham Offspring Study. AB - Identification of diet and lifestyle risk factors for prevention of type 2 diabetes mellitus (T2DM) is of great importance. The specific role of dietary cholesterol (DC) in T2DM risk is unclear. This study uses data from 2192 Framingham Offspring Study subjects to estimate the effects of DC alone and in combination with markers of a healthy diet and other lifestyle factors on fasting glucose and risk of T2DM or impaired fasting glucose (IFG) over 20 years of follow-up. Dietary data were derived from two sets of three-day food records. Statistical methods included mixed linear regression and Cox proportional hazard's modeling to adjust for confounding. There were no statistically significant differences in glucose levels over 20 years of follow-up across DC intake categories (. PMID- 29794967 TI - Carbon Nanohorn Suprastructures on a Paper Support as a Sorptive Phase. AB - This article describes a method for the modification of paper with single-wall carbon nanohorns (SWCNHs) to form stable suprastructures. The SWCNHs form stable dahlia-like aggregates in solution that are then self-assembled into superior structures if the solvent is evaporated. Dipping paper sections into a dispersion of SWCNHs leads to the formation of a thin film that can be used for microextraction purposes. The coated paper can be easily handled with a simple pipette tip, paving the way for disposable extraction units. As a proof of concept, the extraction of antidepressants from urine and their determination by direct infusion mass spectrometry is studied. Limits of detection (LODs) were 10 ng/L for desipramine, amitriptyline, and mianserin, while the precision, expressed as a relative standard deviation, was 7.2%, 7.3%, and 9.8%, respectively. PMID- 29794969 TI - Oral and Dental Health Status among Adolescents with Limited Access to Dental Care Services in Jeddah. AB - The purpose of this study was to assess the prevalence and associated factors of dental caries and periodontal diseases among 14-19-year-old schoolchildren with limited access to dental care services. A cross sectional study design was conducted during field visits to seven governmental schools in Al-Khomrah district, South Jeddah, over the period from September 2015 to May 2016. Clinical examinations and administered questionnaires were carried out in mobile dental clinics. The dentists carried out oral examinations using the dental caries index (DMFT), the simplified oral hygiene index (OHI-S), and the community periodontal index for treatment needs (CPITN). Statistical analyses were performed using SPSS 20. A total of 734 schoolchildren were examined. The prevalence of decayed teeth was 79.7% and was significantly higher among boys (88.9%) than girls (69.0%). About 11% of students had missing teeth, with a significantly higher figure among females than males (15.9% versus 7.3%); 19.8% of students had filled teeth. Moreover, a DMFT of seven or more was significantly more prevalent among males (43.3%) than females (26.8%), while the percentage of females with sound teeth was significantly higher than for males (20.4% and 9.6% respectively). The CPITN revealed 0, 1 and 2 scores among 14.6%, 78.2%, and 41.6% respectively. Males had a significantly higher percentage of healthy periodontal condition (23.8%) than females (3.8%). Dental caries prevalence was moderate to high, calculus and gingival bleeding were widespread among schoolchildren, and were more prevalent among students with low socioeconomic status. PMID- 29794968 TI - Nanoparticle-Mediated Therapeutic Agent Delivery for Treating Metastatic Breast Cancer-Challenges and Opportunities. AB - Breast cancer (BC) is the second leading cause of cancer-related death in American women and more than 90% of BC-related death is caused by metastatic BC (MBC). This review stresses the limited success of traditional therapies as well as the use of nanomedicine for treating MBC. Understanding the biological barriers of MBC that nanoparticle in vivo trafficking must overcome could provide valuable new insights for translating nanomedicine from the bench side to the bedside. A view about nanomedicine applied in BC therapy has been summarized with their present status, which is gaining attention in the clinically-applied landscape. The progressions of drug/gene delivery systems, especially the status of their preclinical or clinical trials, are also discussed. Here we highlight that the treatment of metastasis, in addition to the extensively described inhibition of primary tumor growth, is an indispensable requirement for nanomedicine. Along with more innovations in material chemistry and more progressions in biology, nanomedicine will constantly supply more exciting new approaches for targeted drug/gene delivery against MBC. PMID- 29794971 TI - Fabrication of alpha-Fe/Fe3C/Woodceramic Nanocomposite with Its Improved Microwave Absorption and Mechanical Properties. AB - Furan resin and fir powder pretreated by FeCl3 and aqueous ammonia solution were used to fabricate alpha-Fe/Fe3C/woodceramic nanocomposite. The bands of the pretreated wood powder were characterized by Fourier transform infrared spectroscopy (FTIR). The structural characterization of the nanocomposites was performed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The microwave absorption of the nanocomposites was measured by a vector network analyzer in the range of 2-18 GHz. The mechanical properties of the composites were also investigated. XRD and SEM results show that the alpha-Fe and Fe3C nanoparticles are in-situ generated and disperse in the matrix of the woodceramic. The diameters of these nanoparticles increase with the increasing of concentration of FeCl3 solution. The experimental results show that both the complex permittivity and the complex permeability of alpha-Fe/Fe3C/woodceramic nanocomposites increase as the concentration of FeCl3 solution increases. The composites pretreated with 0.60 mol.L-1 FeCl3 have the best absorption properties. The maximum value of reflection loss (RL) at 3 mm thickness reaches 25.60 dB at 10.16 GHz and the bandwidth below -10 dB is about 2.5 GHz. Compared to woodceramic, the bending strength and compressive strength of alpha Fe/Fe3C/woodceramic nanocomposites increase by 22.5% and 18.7% at most, respectively. PMID- 29794970 TI - Application of CRISPR/Cas9 Gene Editing System on MDV-1 Genome for the Study of Gene Function. AB - Marek's disease virus (MDV) is a member of alphaherpesviruses associated with Marek's disease, a highly contagious neoplastic disease in chickens. Complete sequencing of the viral genome and recombineering techniques using infectious bacterial artificial chromosome (BAC) clones of Marek's disease virus genome have identified major genes that are associated with pathogenicity. Recent advances in CRISPR/Cas9-based gene editing have given opportunities for precise editing of the viral genome for identifying pathogenic determinants. Here we describe the application of CRISPR/Cas9 gene editing approaches to delete the Meq and pp38 genes from the CVI988 vaccine strain of MDV. This powerful technology will speed up the MDV gene function studies significantly, leading to a better understanding of the molecular mechanisms of MDV pathogenesis. PMID- 29794972 TI - DsSWEET17, a Tonoplast-Localized Sugar Transporter from Dianthus spiculifolius, Affects Sugar Metabolism and Confers Multiple Stress Tolerance in Arabidopsis. AB - Plant SWEETs (Sugars Will Eventually be Exported Transporters) affect the growth of plants by regulating the transport of sugar from source to sink and its intracellular transport between different organelles. In this study, DsSWEET17 from Dianthus spiculifolius was identified and characterized. Real-time quantitative PCR analysis revealed that the expression of DsSWEET17 was affected by exogenous application of fructose and glucose as well as under salt, osmotic, and oxidation stress. Colocalization experiments showed that the DsSWEET17-GFP (green fluorescent protein) fusion protein was localized to the FM4-64-labeled tonoplasts in Arabidopsis. Compared to the wild type, the transgenic Arabidopsis seedlings overexpressing DsSWEET17 had longer roots, greater fresh weight, and a faster root growth upon exogenous application of fructose. Furthermore, transgenic Arabidopsis seedlings had significantly higher fructose accumulation than was observed for the wild-type seedlings. The analysis of root length revealed that transgenic Arabidopsis had higher tolerance to salt, osmotic, and oxidative stresses. Taken together, our results suggest that DsSWEET17 may be a tonoplast sugar transporter, and its overexpression affects sugar metabolism and confers multiple stress tolerance in Arabidopsis. PMID- 29794974 TI - Vehicle Classification Using an Imbalanced Dataset Based on a Single Magnetic Sensor. AB - This paper aims to improve the accuracy of automatic vehicle classifiers for imbalanced datasets. Classification is made through utilizing a single anisotropic magnetoresistive sensor, with the models of vehicles involved being classified into hatchbacks, sedans, buses, and multi-purpose vehicles (MPVs). Using time domain and frequency domain features in combination with three common classification algorithms in pattern recognition, we develop a novel feature extraction method for vehicle classification. These three common classification algorithms are the k-nearest neighbor, the support vector machine, and the back propagation neural network. Nevertheless, a problem remains with the original vehicle magnetic dataset collected being imbalanced, and may lead to inaccurate classification results. With this in mind, we propose an approach called SMOTE, which can further boost the performance of classifiers. Experimental results show that the k-nearest neighbor (KNN) classifier with the SMOTE algorithm can reach a classification accuracy of 95.46%, thus minimizing the effect of the imbalance. PMID- 29794973 TI - Anti-Aging Effect of Chitosan Oligosaccharide on d-Galactose-Induced Subacute Aging in Mice. AB - Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice. PMID- 29794975 TI - Optimization of Production Conditions for Protoplasts and Polyethylene Glycol Mediated Transformation of Gaeumannomyces tritici. AB - Take-all, caused by Gaeumannomyces tritici, is one of the most important wheat root diseases worldwide, as it results in serious yield losses. In this study, G. tritici was transformed to express the hygromycin B phosphotransferase using a combined protoplast and polyethylene glycol (PEG)-mediated transformation technique. Based on a series of single-factor experimental results, three major factors-temperature, enzyme lysis time, and concentration of the lysing enzyme were selected as the independent variables, which were optimized using the response surface methodology. A higher protoplast yield of 9.83 * 107 protoplasts/mL was observed, and the protoplast vitality was also high, reaching 96.27% after optimization. Protoplasts were isolated under the optimal conditions, with the highest transformation frequency (46-54 transformants/MUg DNA). Polymerase chain reaction and Southern blotting detection indicated that the genes of hygromycin phosphotransferase were successfully inserted into the genome of G. tritici. An optimised PEG-mediated protoplast transformation system for G. tritici was established. The techniques and procedures described will lay the foundation for establishing a good mutation library of G. tritici and could be used to transform other fungi. PMID- 29794977 TI - Vitamin K Antagonists and Cognitive Decline in Older Adults: A 24-Month Follow Up. AB - Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 +/- 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted beta = -2.1, p = 0.026), and with a decrease in FAB score after 24 months (adjusted beta = -203.6%, p = 0.010), but not after 12 months (p = 0.659). Using VKAs was not associated with any change in MMSE score at baseline (p = 0.655), after 12 months (p = 0.603), or after 24 months (p = 0.201). In conclusion, we found more severe executive dysfunction at baseline and incident executive decline over 24 months among geriatric patients using VKAs, when compared with their counterparts. PMID- 29794976 TI - Recent Advances in Laser-Ablative Synthesis of Bare Au and Si Nanoparticles and Assessment of Their Prospects for Tissue Engineering Applications. AB - Driven by surface cleanness and unique physical, optical and chemical properties, bare (ligand-free) laser-synthesized nanoparticles (NPs) are now in the focus of interest as promising materials for the development of advanced biomedical platforms related to biosensing, bioimaging and therapeutic drug delivery. We recently achieved significant progress in the synthesis of bare gold (Au) and silicon (Si) NPs and their testing in biomedical tasks, including cancer imaging and therapy, biofuel cells, etc. We also showed that these nanomaterials can be excellent candidates for tissue engineering applications. This review is aimed at the description of our recent progress in laser synthesis of bare Si and Au NPs and their testing as functional modules (additives) in innovative scaffold platforms intended for tissue engineering tasks. PMID- 29794979 TI - A Service-Oriented Middleware for Integrated Management of Crowdsourced and Sensor Data Streams in Disaster Management. AB - The increasing number of sensors used in diverse applications has provided a massive number of continuous, unbounded, rapid data and requires the management of distinct protocols, interfaces and intermittent connections. As traditional sensor networks are error-prone and difficult to maintain, the study highlights the emerging role of "citizens as sensors" as a complementary data source to increase public awareness. To this end, an interoperable, reusable middleware for managing spatial, temporal, and thematic data using Sensor Web Enablement initiative services and a processing engine was designed, implemented, and deployed. The study found that its approach provided effective sensor data-stream access, publication, and filtering in dynamic scenarios such as disaster management, as well as it enables batch and stream management integration. Also, an interoperability analytics testing of a flood citizen observatory highlighted even variable data such as those provided by the crowd can be integrated with sensor data stream. Our approach, thus, offers a mean to improve near-real-time applications. PMID- 29794978 TI - Synthesis, Design, and Structure-Activity Relationship of the Pyrimidone Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase. AB - The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of PfDHODH. The most potent compound, 26, showed high inhibition activity against PfDHODH (IC50 = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (hDHODH). The brand-new inhibitor scaffold targeting PfDHODH reported in this work may lead to the discovery of new antimalarial agents. PMID- 29794980 TI - Do Physical Activity Friendly Neighborhoods Affect Community Members Equally? A Cross-Sectional Study. AB - An activity-friendly environment may increase physical activity (PA) levels and decrease sedentary behavior (SB). This study investigated associations between socio-demographic characteristics, health-related quality of life (HRQoL), perceived environment and objectively measured PA outcomes. Socio-demographic characteristics were assessed using a questionnaire and HRQoL was measured using the EQ-5D. The Neighborhood Environment Walkability Scale (NEWS-A) was used to assess the perceived environment. SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured using the Actigraph GT3X+. Data from 622 Dutch adults were used in multivariate linear regression analyses to investigate associations between NEWS-A and PA outcomes. Analyses were controlled for socio-demographic characteristics and HRQoL. The presence of attractive buildings was associated with less SB (beta = -0.086, p < 0.01) and more MVPA (beta = 0.118, p < 0.01). Presence of destinations within walking distance was also positively associated with MVPA (beta = 0.106, p < 0.01). Less crime was associated with less MVPA (beta = 0.092, p < 0.05). Interactions between personal and environmental characteristics showed that the absence of PA-hindering characteristics (e.g., heavy traffic) was associated with less SB and more MVPA, but only for residents with problems regarding pain and usual activities. The presence of PA facilitating characteristics (e.g., aesthetics and destinations) was associated with less SB, more LPA and more MVPA but only for the more advantaged people in society. Results suggest that to reduce health inequalities, it would be more helpful to remove barriers rather than introduce PA facilitating characteristics. PMID- 29794981 TI - Reorganization of the Y Chromosomes Enhances Divergence in Israeli Mole Rats Nannospalax ehrenbergi (Spalacidae, Rodentia): Comparative Analysis of Meiotic and Mitotic Chromosomes. AB - The Y chromosome in mammals is variable, even in closely related species. Middle East blind mole rats Nannospalax ehrenbergi demonstrate autosomal variability, which probably leads to speciation. Here, we compare the mitotic and meiotic chromosomes of mole rats. For the first time, we studied the behavior of their sex chromosomes in the meiotic prophase I using electron microscopy and immunocytochemical analysis. Unexpectedly, the sex chromosomes of the 52- and 60 chromosome forms of mole rats showed different synaptic and recombination patterns due to distinct locations of the centromeres on the Y chromosomes. The absence of recombination in the 60-chromosome form, the asymmetric synapsis, and the short-term disturbance in the synaptic co-orientation of the telomeric regions of the X and Y chromosomes were revealed as specific features of mole rat sex bivalents. We suggest several scenarios of Y chromosome alteration in connection with species differentiation in mole rats. PMID- 29794982 TI - Performance Comparisons of Polymer Semiconductors Synthesized by Direct (Hetero)Arylation Polymerization (DHAP) and Conventional Methods for Organic Thin Film Transistors and Organic Photovoltaics. AB - C-C bond forming reactions are central to the construction of pi-conjugated polymers. Classical C-C bond forming reactions such as the Stille and Suzuki coupling reactions have been widely used in the past for this purpose. More recently, direct (hetero)arylation polymerization (DHAP) has earned a place in the spotlight with an increasing number of pi-conjugated polymers being produced using this atom-economic and more sustainable chemistry. As semiconductors in organic electronics, the device performances of the polymers made by DHAP are of great interest and importance. This review compares the device performances of some representative pi-conjugated polymers made using the DHAP method with those made using the conventional C-C bond forming reactions when they are used as semiconductors in organic thin film transistors (OTFTs) and organic photovoltaics (OPVs). PMID- 29794983 TI - Clinical Advances in Viral-Vectored Influenza Vaccines. AB - Influenza-virus-mediated disease can be associated with high levels of morbidity and mortality, particularly in younger children and older adults. Vaccination is the primary intervention used to curb influenza virus infection, and the WHO recommends immunization for at-risk individuals to mitigate disease. Unfortunately, influenza vaccine composition needs to be updated annually due to antigenic shift and drift in the viral immunogen hemagglutinin (HA). There are a number of alternate vaccination strategies in current development which may circumvent the need for annual re-vaccination, including new platform technologies such as viral-vectored vaccines. We discuss the different vectored vaccines that have been or are currently in clinical trials, with a forward looking focus on immunogens that may be protective against seasonal and pandemic influenza infection, in the context of viral-vectored vaccines. We also discuss future perspectives and limitations in the field that will need to be addressed before new vaccines can significantly impact disease levels. PMID- 29794985 TI - A Rare De Novo RAI1 Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation. AB - Deletions and mutations involving the Retinoic Acid Induced 1 (RAI1) gene at 17p11.2 cause Smith-Magenis syndrome (SMS). Here we report a patient with autism as the main clinical presentation, with some SMS-like features and a rare de novo RAI1 gene mutation, c.3440G > A (p.R1147Q). We functionally characterized the RAI1 p.R1147Q mutant protein. The mutation, located near the nuclear localization signal, had no effect on the subcellular localization of the mutant protein. However, similar to previously reported RAI1 missense mutations in SMS patients, the RAI1 p.R1147Q mutant protein showed a significant deficiency in activating in vivo transcription of a reporter gene driven by a BDNF (brain-derived neurotrophic factor) intronic enhancer. In addition, expression of other genes associated with neurobehavioral abnormalities and/or neurodevelopmental disorders were found to be altered in this patient. These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. PMID- 29794986 TI - Understanding Eating Behavior during the Transition from Adolescence to Young Adulthood: A Literature Review and Perspective on Future Research Directions. AB - INTRODUCTION: Eating behavior often becomes unhealthier during the transition from adolescence to young adulthood, but not much is known about the factors that drive this change. We assess the available evidence on this topic through a literature review and pay special attention to the research designs employed in the studies available as well as the modifiability of the factors investigated in previous research. METHOD: We systematically conducted a scoping review by searching literature published in or after 2000 in three databases that described one or more factors associated with eating behavior or changes in eating behavior during the transition from adolescence to adulthood in the general population. Our search identified eighteen articles meeting these inclusion criteria. The socio-ecological DONE (Determinants of Nutrition and Eating) framework, a recently developed dynamic framework of factors shaping dietary behavior, was used to structure and categorize the factors identified. RESULTS: Most factors identified in the literature were individual-level factors (67%) such as food beliefs, time constraints, and taste preferences; on the other hand, interpersonal-level factors (e.g., social support), environmental-level factors (e.g., product characteristics) and policy-level factors (e.g., market regulations) have been reported on less extensively. Furthermore, most factors discussed in the literature have been classified in the DONE framework as not easily modifiable. Moreover, previous studies largely used static research designs and focused primarily on one specific population (US freshmen). DISCUSSION: This systematic scoping review identified several gaps in the available literature that hinder insight into the drivers of eating behavior (change) during the transition from adolescence to young adulthood. There is an urgent need for research on broader populations, employing dynamic repeated measures designs, and taking modifiability of factors into account. PMID- 29794984 TI - Attenuation of Metabolic Syndrome by EPA/DHA Ethyl Esters in Testosterone Deficient Obese Rats. AB - Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8 9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation. PMID- 29794987 TI - Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection. AB - Our laboratory has serially reported on the virologic and immunopathologic features of a cohort of experimental feline immunodeficiency virus (FIV)-infected cats for more than eight years. At 8.09 years post infection (PI), one of these animals entered the terminal stage of infection, characterized by undulating hyperthermia, progressive anorexia, weight loss, and pancytopenia; the animal was not responsive to therapeutic interventions, necessitating euthanasia six weeks later (8.20 years PI). Subsequent analyses indicated that neoplastic lymphocytes infiltrated multiple cervical lymph nodes and a band-like region of the mucosal lamina propria within a segment of the intestine. Immunohistochemistry and T cell clonality testing determined that the nodal and intestinal lesions were independently arising from CD3 T cell lymphomas. In-situ RNA hybridization studies indicated that diffuse neoplastic lymphocytes from the cervical lymph node contained abundant viral nucleic acid, while viral nucleic acid was not detectable in lymphocytes from the intestinal lymphoma lesion. The proviral long terminal repeat (LTR) was amplified and sequenced from multiple anatomic sites, and a common clone containing a single nucleotide polymorphism was determined to be defective in response to phorbol myristate acetate (PMA)-mediated promoter activation in a reporter gene assay. This assay revealed a previously unidentified PMA response element within the FIV U3 region 3' to the TATA box. The possible implications of these results on FIV-lymphoma pathogenesis are discussed. PMID- 29794989 TI - Parallel Processing Transport Model MT3DMS by Using OpenMP. AB - Solute transport modeling resolves advection, dispersion, and chemical reactions in groundwater systems with its accuracy depending on the resolution of domain at all scales, thus the computational efficiency of a simulator becomes a bottleneck for the wide application of numerical simulations. However, the traditional serial numerical simulators have reached their limits for the prohibitive computational time and memory requirement in solving large-scale problems. These limitations have greatly hindered the wide application of groundwater solute transport modeling. Thus, the development of an efficient method for handling large-scale groundwater solute transport simulation is urgently required. In this study, we developed and assessed a parallelized MT3DMS (Modular Three-Dimensional Multispecies Transport Model) by using OpenMP (Open specifications for Multi Processing) to accelerate the solute transport simulation process. The parallelization was achieved by adding OpenMP compile directives (i.e., defining various types of parallel regions) into the most time-consuming packages, including the Advection package (ADV), Dispersion package (DSP), and Generalized Conjugate Gradient Solver package (GCG). This allows parallel processing on shared-memory multiprocessors, i.e., both the memory requirement and computing efforts are automatically distributed among all processors. Moreover, we discussed two different parallelization strategies for handling numerical models with either many layers or few layers. The performance of parallelized MT3DMS was assessed by two benchmark numerical models with different model domain sizes via a workstation with two quad-core processors. Results showed that the running time of parallelized MT3DMS can be 4.15 times faster than that using sequential MT3DMS. The effects of using different preconditioners (procedures that transform a given problem into a form that is more suitable for numerical solving methods) in the GCG package were additionally evaluated. The modified strategy for handling numerical models with few layers also achieved satisfactory results with running time two times faster than that via sequential simulation. Thus, the proposed parallelization allows high-resolution groundwater transport simulation with higher efficiency for large-scale or multimillion-cell simulation problems. PMID- 29794988 TI - Multigene Family of Pore-Forming Toxins from Sea Anemone Heteractis crispa. AB - Sea anemones produce pore-forming toxins, actinoporins, which are interesting as tools for cytoplasmic membranes study, as well as being potential therapeutic agents for cancer therapy. This investigation is devoted to structural and functional study of the Heteractis crispa actinoporins diversity. Here, we described a multigene family consisting of 47 representatives expressed in the sea anemone tentacles as prepropeptide-coding transcripts. The phylogenetic analysis revealed that actinoporin clustering is consistent with the division of sea anemones into superfamilies and families. The transcriptomes of both H. crispa and Heteractis magnifica appear to contain a large repertoire of similar genes representing a rapid expansion of the actinoporin family due to gene duplication and sequence divergence. The presence of the most abundant specific group of actinoporins in H. crispa is the major difference between these species. The functional analysis of six recombinant actinoporins revealed that H. crispa actinoporin grouping was consistent with the different hemolytic activity of their representatives. According to molecular modeling data, we assume that the direction of the N-terminal dipole moment tightly reflects the actinoporins' ability to possess hemolytic activity. PMID- 29794991 TI - Experimental Investigation of Principal Residual Stress and Fatigue Performance for Turned Nickel-Based Superalloy Inconel 718. AB - Residual stresses of turned Inconel 718 surface along its axial and circumferential directions affect the fatigue performance of machined components. However, it has not been clear that the axial and circumferential directions are the principle residual stress direction. The direction of the maximum principal residual stress is crucial for the machined component service life. The present work aims to focuses on determining the direction and magnitude of principal residual stress and investigating its influence on fatigue performance of turned Inconel 718. The turning experimental results show that the principal residual stress magnitude is much higher than surface residual stress. In addition, both the principal residual stress and surface residual stress increase significantly as the feed rate increases. The fatigue test results show that the direction of the maximum principal residual stress increased by 7.4%, while the fatigue life decreased by 39.4%. The maximum principal residual stress magnitude diminished by 17.9%, whereas the fatigue life increased by 83.6%. The maximum principal residual stress has a preponderant influence on fatigue performance as compared to the surface residual stress. The maximum principal residual stress can be considered as a prime indicator for evaluation of the residual stress influence on fatigue performance of turned Inconel 718. PMID- 29794993 TI - Comparing the Recombinant Protein Production Potential of Planktonic and Biofilm Cells. AB - Recombinant protein production in bacterial cells is commonly performed using planktonic cultures. However, the natural state for many bacteria is living in communities attached to surfaces forming biofilms. In this work, a flow cell system was used to compare the production of a model recombinant protein (enhanced green fluorescent protein, eGFP) between planktonic and biofilm cells. The fluorometric analysis revealed that when the system was in steady state, the average specific eGFP production from Escherichia coli biofilm cells was 10-fold higher than in planktonic cells. Additionally, epifluorescence microscopy was used to determine the percentage of eGFP-expressing cells in both planktonic and biofilm populations. In steady state, the percentage of planktonic-expressing cells oscillated around 5%, whereas for biofilms eGFP-expressing cells represented on average 21% of the total cell population. Therefore, the combination of fluorometric and microscopy data allowed us to conclude that E. coli biofilm cells can have a higher recombinant protein production capacity when compared to their planktonic counterparts. PMID- 29794992 TI - Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment. AB - Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development. PMID- 29794990 TI - Anti-Metastatic Effects of Antrodan with and without Cisplatin on Lewis Lung Carcinomas in a Mouse Xenograft Model. AB - Antrodan, a unique protein-bound polysaccharide derived from the fungal mycelia of Antrodia cinnamomea, has been reported to exhibit antitumor and anti metastatic effects on Lewis lung carcinoma (LLC) cells through direct action and immunomodulation in vitro. In this study, we investigated the combined treatment of antrodan with an anti-cancer drug-cisplatin-and its underlying molecular mechanisms of action in a mouse xenograft tumor model. C57BL/6 mice were implanted (s.c.) with LLCs for nine days, before administration with only antrodan (20 mg/kg and 40 mg/kg; p.o.) daily, only cisplatin (1 mg/kg; i.p.) twice per week, or a combination of both for an additional 28 days. As expected, antrodan on its own significantly inhibited metastasis of lung and liver tissues, while treatment with cisplatin only merely inhibited metastasis of the liver. Antrodan exhibited efficient adjuvant therapy in combination with cisplatin, by inhibiting the activities of the plasma urokinase plasminogen activator (uPA) and the liver matrix metalloproteinase 9 (MMP-9), as well as by inhibiting the phosphorylation of p38 and extracellular signal-regulated kinase 2 (ERK2) in lung and liver tissues. In addition, antrodan effectively ameliorated cisplatin induced kidney dysfunction when treated combinatorially, as evidenced by a decrease in cisplatin-induced blood urea nitrogen (BUN) levels in plasma and in the level of p38 phosphorylation in the kidney. Mechanistically, the actions of antrodan on its own involved (i) reducing the activities of uPA and MMP-2 and -9 in plasma; (ii) reducing protein expression of MMP-2/9, and the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 in lung and liver tissues; and (iii) enhancing immune system functions resulting in the promotion of an anti-metastatic response through immunomodulation, by increasing interferon gamma (IFN-gamma) levels and decreasing interleukin-6 (IL-6) levels in plasma. These results demonstrated that antrodan provides a novel, complementary therapeutic strategy against cancer metastasis, by attenuating the activities of MMP-2 and -9 through the modulation of STAT3/MAPK/ERK/JNK signaling pathways, and of the host's immune system. PMID- 29794994 TI - A Statistical Approach to Detect Jamming Attacks in Wireless Sensor Networks. AB - Wireless Sensor Networks (WSNs), in recent times, have become one of the most promising network solutions with a wide variety of applications in the areas of agriculture, environment, healthcare and the military. Notwithstanding these promising applications, sensor nodes in WSNs are vulnerable to different security attacks due to their deployment in hostile and unattended areas and their resource constraints. One of such attacks is the DoS jamming attack that interferes and disrupts the normal functions of sensor nodes in a WSN by emitting radio frequency signals to jam legitimate signals to cause a denial of service. In this work we propose a step-wise approach using a statistical process control technique to detect these attacks. We deploy an exponentially weighted moving average (EWMA) to detect anomalous changes in the intensity of a jamming attack event by using the packet inter-arrival feature of the received packets from the sensor nodes. Results obtained from a trace-driven simulation show that the proposed solution can efficiently and accurately detect jamming attacks in WSNs with little or no overhead. PMID- 29794995 TI - Effect of Ethanol on Ag@Mesoporous Silica Formation by In Situ Modified Stober Method. AB - Tunable core-shell Ag@Mesoporous SiO2 spheres were synthesized via an in situ modified Stober approach by varying the amount of ethanol (EtOH) expanding their potentials in many applications. Mesoporous silica was generated by adding tetraethyl orthosilicate (TEOS) to the mixture of colloidal Ag particles prepared by reducing silver nitrate (AgNO3) with L-ascorbic acid and using hexadecyltrimethylammonium bromide (CTAB) as a template at the presence of ethanol and sodium hydroxide (NaOH) at pH 10 as a catalyst. The average sizes of the Ag cores at the three increasing volumes of ethanol were ~47 +/- 6, 36 +/- 4, and 11 +/- 5 nm, while the silica particle size and the thickness of the silica shells increased, resulting in a blueshift of localized surface plasmon resonances (LSPR) of the Ag NPs. The corresponding specific surface areas of silica particles were 356 +/- 10, 419 +/- 20 and 490 +/- 25 m2 g-1, and average pore diameters varied from 5.7, 5.0 to 3.3 nm according to BET and BJH analyses. TEM studies confirmed the core-shell structure, pore sizes and shapes of mesoporous shells. The dissolution tests demonstrated that the release of Ag from the powder samples is pH-sensitive and time-dependent. PMID- 29794996 TI - Accumulation of Heavy Metals in Roadside Soil in Urban Area and the Related Impacting Factors. AB - Heavy metal contamination in roadside soil due to traffic emission has been recognized for a long time. However, seldom has been reported regarding identification of critical factors influencing the accumulation of heavy metals in urban roadside soils due to the frequent disturbances such as the repair of damaged roads and green belt maintanance. Heavy metals in the roadside soils of 45 roads in Xihu district, Hangzhou city were investigated. Results suggested the accumulation of Cu, Pb, Cd, Cr, and Zn in roadside soil was affected by human activity. However, only two sites had Pb and Zn excessing the standards for residential areas, respectively, according to Chinese Environmental Quality Standards for soils. The concentrations of Cu, Pb, Cd, and Zn were significantly and positively correlated to soil pH and organic matter. An insignificant correlation between the age of the roads or vegetation cover types and the concentration of heavy metals was found although they were reported closely relating to the accumulation of heavy metals in roadside soils of highways. The highest Pb, Cd, and Cr taking place in sites with heavy traffic and significant differences in the concentrations of Cu, Pb, Cd, and Zn among the different categories of roads suggested the contribution of traffic intensity. However, it was difficult to establish a quantitative relationship between traffic intensity and the concentrations of heavy metals in the roadside soil. It could be concluded that impaction of traffic emission on the accumulation of heavy metals in roadside soils in urban area was slight and soil properties such as pH and organic matters were critical factors influencing the retention of heavy metals in soils. PMID- 29794997 TI - Enhanced Tribological and Bacterial Resistance of Carbon Nanotube with Ceria- and Silver-Incorporated Hydroxyapatite Biocoating. AB - Pertaining to real-life applications (by scaling up) of hydroxyapatite (HA)-based materials, herein is a study illustrating the role of carbon nanotube (CNT) reinforcement with ceria (CeO2) and silver (Ag) in HA on titanium alloy (TiAl6V4) substrate, utilizing the plasma-spraying processing technique, is presented. When compared with pure HA coating enhanced hardness (from 2.5 to 5.8 GPa), elastic modulus (from 110 to 171 GPa), and fracture toughness (from 0.7 to 2.2 MPa.m1/2) elicited a reduced wear rate from 55.3 * 10-5 mm3.N-1.m-1 to 2.1 * 10-5 mm3.N-1.m 1 in HA-CNT-CeO2-Ag. Besides, an order of magnitude lower Archard's wear constant and a 41% decreased shear stress by for HA-CNT-CeO2-Ag coating depicted the effect of higher hardness and modulus of a material to control its wear phenomenon. Antibacterial property of 46% (bactericidal) is ascribed to Ag in addition to CNT-CeO2 in HA. Nonetheless, the composite coating also portrayed exaggerated L929 fibroblast cell growth (4.8 times more than HA), which was visualized as flat and elongated cells with multiple filopodial protrusions. Hence, synthesis of a material with enhanced mechanical integrity resulting in tribological resistance and cytocompatible efficacy was achieved, thereupon making HA-CNT-CeO2-Ag a scalable potent material for real-life load-bearing implantable bio-coating. PMID- 29794998 TI - Dynamical Properties of Postural Control in Obese Community-Dwelling Older Adults ?. AB - Postural control is a key aspect in preventing falls. The aim of this study was to determine if obesity affected balance in community-dwelling older adults and serve as an indicator of fall risk. The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a longitudinal assessment of their fall history. The standing postural balance was measured for 98 participants with a Body Mass Index (BMI) ranging from 18 to 63 kg/m2, using a force plate and an inertial measurement unit affixed at the sternum. Participants' fall history was recorded over 2 years and participants with at least one fall in the prior year were classified as fallers. The results suggest that body weight/BMI is an additional risk factor for falling in elderly persons and may be an important marker for fall risk. The linear variables of postural analysis suggest that the obese fallers have significantly higher sway area and sway ranges, along with higher root mean square and standard deviation of time series. Additionally, it was found that obese fallers have lower complexity of anterior-posterior center of pressure time series. Future studies should examine more closely the combined effect of aging and obesity on dynamic balance. PMID- 29794999 TI - Targeted Tumor Therapy Remixed-An Update on the Use of Small-Molecule Drugs in Combination Therapies. AB - Over the last decade, the treatment of tumor patients has been revolutionized by the highly successful introduction of novel targeted therapies, in particular small-molecule kinase inhibitors and monoclonal antibodies, as well as by immunotherapies. Depending on the mutational status, BRAF and MEK inhibitor combinations or immune checkpoint inhibitors are current first-line treatments for metastatic melanoma. However, despite great improvements of survival rates limitations due to tumor heterogeneity, primary and acquired therapy resistance, immune evasion, and economical considerations will need to be overcome. Accordingly, ongoing clinical trials explore the individualized use of small molecule drugs in new targeted therapy combinations based on patient parameters and tumor biopsies. With focus on melanoma therapy this review aims at providing a comprehensive overview of such novel alternative and combinational therapy strategies currently emerging from basic research. The molecular principles and drug classes that may hold promise for improved tumor therapy combination regimens including kinase inhibition, induction of apoptosis, DNA-damage response inhibition, epigenetic reprogramming, telomerase inhibition, redox modulation, metabolic reprogramming, proteasome inhibition, cancer stem cell transdifferentiation, immune cell signaling modulation, and others, are explained in brief. In addition, relevant targeted therapy combinations in current clinical trials and individualized treatment strategies are highlighted. PMID- 29795001 TI - Polymerizable Microsphere-Induced High Mechanical Strength of Hydrogel Composed of Acrylamide. AB - Polymerizable microspheres are introduced into acrylamide to prepare the high mechanical strength hydrogels with a novel three-dimensional pore structure. Rheological properties, compressive stress-strain, tensile property, and compression strength of three different types of hydrogels were investigated. Moreover, a scanning electron microscope (SEM) was adopted to observe the three dimension network structure of three different types of hydrogels. The test results illustrated that viscous moduli (G") and elastic moduli (G') of a hydrogel containing polymerizable microspheres (P) reached maximum values, compared to the normal hydrogel (N) and the composite hydrogel containing ordinary microspheres (O). When the hydrogels were squeezed, the N was easily fractured under high strain (99%), whereas the P was not broken, and quickly recovered its initial morphology after the release of load. The P showed excellent tensile properties, with an elongation at break up to 90% and a tensile strength greater than 220 g. The compression strength of the N was 100.44 kPa.m 1, while the resulting strength of P was enhanced to be 248.00 kPa.m-1. Therefore, the various performances of N were improved by adding polymerizable microspheres. In addition, the SEM images indicated that N has a general three dimensional network structure; the conventional network structure did not exist in the P, which has a novel three-dimensional pore structure in the spherical projection and very dense channels, which led to the compaction of the space between the three-dimensional pore network layers and reduced the flowing of free water wrapped in the network. Therefore, the mechanical strength of hydrogel was enhanced. PMID- 29795002 TI - Microstructure and Thermal Reliability of Microcapsules Containing Phase Change Material with Self-Assembled Graphene/Organic Nano-Hybrid Shells. AB - In recent decades, microcapsules containing phase change materials (microPCMs) have been the center of much attention in the field of latent thermal energy storage. The aim of this work was to prepare and investigate the microstructure and thermal conductivity of microPCMs containing self-assembled graphene/organic hybrid shells. Paraffin was used as a phase change material, which was successfully microencapsulated by graphene and polymer forming hybrid composite shells. The physicochemical characters of microPCM samples were investigated including mean size, shell thickness, and chemical structure. Scanning electron microscope (SEM) results showed that the microPCMs were spherical particles and graphene enhanced the degree of smoothness of the shell surface. The existence of graphene in the shells was proved by using the methods of X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). It was found that graphene hybrid shells were constructed by forces of electric charge absorption and long-molecular entanglement. MicroPCMs with graphene had a higher degradation temperature of 300 degrees C. Graphene greatly enhanced the thermal stability of microPCMs. The thermal conductivity tests indicated that the phase change temperature of microPCMs was regulated by the graphene additive because of enhancement of the thermal barrier of the hybrid shells. Differential scanning calorimetry (DSC) tests proved that the latent thermal energy capability of microPCMs had been improved with a higher heat conduction rate. In addition, infrared thermograph observations implied that the microPCMs had a sensitivity response to heat during the phase change cycling process because of the excellent thermal conductivity of graphene. PMID- 29795000 TI - In-Vivo NMR Spectroscopy: A Powerful and Complimentary Tool for Understanding Environmental Toxicity. AB - Part review, part perspective, this article examines the applications and potential of in-vivo Nuclear Magnetic Resonance (NMR) for understanding environmental toxicity. In-vivo NMR can be applied in high field NMR spectrometers using either magic angle spinning based approaches, or flow systems. Solution-state NMR in combination with a flow system provides a low stress approach to monitor dissolved metabolites, while magic angle spinning NMR allows the detection of all components (solutions, gels and solids), albeit with additional stress caused by the rapid sample spinning. With in-vivo NMR it is possible to use the same organisms for control and exposure studies (controls are the same organisms prior to exposure inside the NMR). As such individual variability can be reduced while continual data collection over time provides the temporal resolution required to discern complex interconnected response pathways. When multidimensional NMR is combined with isotopic labelling, a wide range of metabolites can be identified in-vivo providing a unique window into the living metabolome that is highly complementary to more traditional metabolomics studies employing extracts, tissues, or biofluids. PMID- 29795003 TI - Yeast Derived LysA2 Can Control Bacterial Contamination in Ethanol Fermentation. AB - Contamination of fuel-ethanol fermentations continues to be a significant problem for the corn and sugarcane-based ethanol industries. In particular, members of the Lactobacillaceae family are the primary bacteria of concern. Currently, antibiotics and acid washing are two major means of controlling contaminants. However, antibiotic use could lead to increased antibiotic resistance, and the acid wash step stresses the fermenting yeast and has limited effectiveness. Bacteriophage endolysins such as LysA2 are lytic enzymes with the potential to contribute as antimicrobials to the fuel ethanol industries. Our goal was to evaluate the potential of yeast-derived LysA2 as a means of controlling Lactobacillaceae contamination. LysA2 intracellularly produced by Pichia pastoris showed activity comparable to Escherichia coli produced LysA2. Lactic Acid Bacteria (LAB) with the A4alpha peptidoglycan chemotype (L-Lys-D-Asp crosslinkage) were the most sensitive to LysA2, though a few from that chemotype were insensitive. Pichia-expressed LysA2, both secreted and intracellularly produced, successfully improved ethanol productivity and yields in glucose (YPD60) and sucrose-based (sugarcane juice) ethanol fermentations in the presence of a LysA2 susceptible LAB contaminant. LysA2 secreting Sacharomyces cerevisiae did not notably improve production in sugarcane juice, but it did control bacterial contamination during fermentation in YPD60. Secretion of LysA2 by the fermenting yeast, or adding it in purified form, are promising alternative tools to control LAB contamination during ethanol fermentation. Endolysins with much broader lytic spectrums than LysA2 could supplement or replace the currently used antibiotics or the acidic wash. PMID- 29795006 TI - Comment on Thigpen D. et al. The Role of Ultrasound in Screening Dense Breasts-A Review of the Literature and Practical Solutions for Implementation. Diagnostics 2018, 8, 20. AB - We read with interest the article by Thigpen et al. [1]. With 34 states now having some form of density inform legislation[...]. PMID- 29795005 TI - High-Fructose Corn-Syrup-Sweetened Beverage Intake Increases 5-Hour Breast Milk Fructose Concentrations in Lactating Women. AB - This study determined the effects of consuming a high-fructose corn syrup (HFCS) sweetened beverage on breast milk fructose, glucose, and lactose concentrations in lactating women. At six weeks postpartum, lactating mothers (n = 41) were randomized to a crossover study to consume a commercially available HFCS sweetened beverage or artificially sweetened control beverage. At each session, mothers pumped a complete breast milk expression every hour for six consecutive hours. The baseline fasting concentrations of breast milk fructose, glucose, and lactose were 5.0 +/- 1.3 ug/mL, 0.6 +/- 0.3 mg/mL, and 6.8 +/- 1.6 g/dL, respectively. The changes over time in breast milk sugars were significant only for fructose (treatment * time, p < 0.01). Post hoc comparisons showed the HFCS sweetened beverage vs. control beverage increased breast milk fructose at 120 min (8.8 +/- 2.1 vs. 5.3 +/- 1.9 ug/mL), 180 min (9.4 +/- 1.9 vs. 5.2 +/- 2.2 ug/mL), 240 min (7.8 +/- 1.7 vs. 5.1 +/- 1.9 ug/mL), and 300 min (6.9 +/- 1.4 vs. 4.9 +/- 1.9 ug/mL) (all p < 0.05). The mean incremental area under the curve for breast milk fructose was also different between treatments (14.7 +/- 1.2 vs. -2.60 +/- 1.2 ug/mL * 360 min, p < 0.01). There was no treatment * time interaction for breast milk glucose or lactose. Our data suggest that the consumption of an HFCS sweetened beverage increased breast milk fructose concentrations, which remained elevated up to five hours post-consumption. PMID- 29795007 TI - Acquiring Respiration Rate from Photoplethysmographic Signal by Recursive Bayesian Tracking of Intrinsic Modes in Time-Frequency Spectra. AB - Respiration rate (RR) provides useful information for assessing the status of a patient. We propose RR estimation based on photoplethysmography (PPG) because the blood perfusion dynamics are known to carry information on breathing, as respiration-induced modulations in the PPG signal. We studied the use of amplitude variability of transmittance mode finger PPG signal in RR estimation by comparing four time-frequency (TF) representation methods of the signal cascaded with a particle filter. The TF methods compared were short-time Fourier transform (STFT) and three types of synchrosqueezing methods. The public VORTAL database was used in this study. The results indicate that the advanced frequency reallocation methods based on synchrosqueezing approach may present improvement over linear methods, such as STFT. The best results were achieved using wavelet synchrosqueezing transform, having a mean absolute error and median error of 2.33 and 1.15 breaths per minute, respectively. Synchrosqueezing methods were generally more accurate than STFT on most of the subjects when particle filtering was applied. While TF analysis combined with particle filtering is a promising alternative for real-time estimation of RR, artefacts and non-respiration-related frequency components remain problematic and impose requirements for further studies in the areas of signal processing algorithms an PPG instrumentation. PMID- 29795004 TI - The Eye, Oxidative Damage and Polyunsaturated Fatty Acids. AB - Polyunsaturated fatty acids (PUFA) are known to have numerous beneficial effects, owing to their anti-inflammatory and antioxidant properties. From a metabolic standpoint, the mitochondria play a fundamental role in cellular homeostasis, and oxidative stress can affect their functioning. Indeed, the mitochondria are the main source of ROS, and an imbalance between ROS and antioxidant defenses leads to oxidative stress. In addition, aging, the decline of cellular functions, and continual exposure to light underlie many diseases, particularly those of the eye. Long-term exposure to insults, such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins, contribute to oxidative damage in ocular tissues and expose the aging eye to considerable risk of pathological consequences of oxidative stress. Ample antioxidant defenses responsible for scavenging free radicals are essential for redox homeostasis in the eye, indeed, eye tissues, starting from the tear film, which normally are exposed to high oxygen levels, have strong antioxidant defenses that are efficient for protecting against ROS-related injuries. On the contrary, instead, the trabecular meshwork is not directly exposed to light and its endothelial cells are poorly equipped with antioxidant defenses. All this makes the eye a target organ of oxidative damage. This review focuses on the role of the polyunsaturated fatty acids in the human eye, particularly in such pathologies as dry eye, glaucoma, and macular degeneration, in which dietary PUFA supplementation can be a valid therapeutic aid. PMID- 29795008 TI - Rapid Production of Mn3O4/rGO as an Efficient Electrode Material for Supercapacitor by Flame Plasma. AB - Benefiting from good ion accessibility and high electrical conductivity, graphene based material as electrodes show promising electrochemical performance in energy storage systems. In this study, a novel strategy is devised to prepare binder free Mn3O4-reduced graphene oxide (Mn3O4/rGO) electrodes. Well-dispersed and homogeneous Mn3O4 nanosheets are grown on graphene layers through a facile chemical co-precipitation process and subsequent flame procedure. This obtained Mn3O4/rGO nanostructures exhibit excellent gravimetric specific capacitance of 342.5 F g-1 at current density of 1 A g-1 and remarkable cycling stability of 85.47% capacitance retention under 10,000 extreme charge/discharge cycles at large current density. Furthermore, an asymmetric supercapacitor assembled using Mn3O4/rGO and activated graphene (AG) delivers a high energy density of 27.41 Wh kg-1 and a maximum power density of 8 kW kg-1. The material synthesis strategy presented in this study is facile, rapid and simple, which would give an insight into potential strategies for large-scale applications of metal oxide/graphene and hold tremendous promise for power storage applications. PMID- 29795009 TI - Genome-Wide Identification and Expression Profiling Analysis of the Xyloglucan Endotransglucosylase/Hydrolase Gene Family in Tobacco (Nicotiana tabacum L.). AB - Xyloglucan endotransglucosylase/hydrolase genes (XTHs) encode enzymes required for the reconstruction and modification of xyloglucan backbones, which will result in changes of cell wall extensibility during growth. A total of 56 NtXTH genes were identified from common tobacco, and 50 cDNA fragments were verified by PCR amplification. The 56 NtXTH genes could be classified into two subfamilies: Group I/II and Group III according to their phylogenetic relationships. The gene structure, chromosomal localization, conserved protein domains prediction, sub cellular localization of NtXTH proteins and evolutionary relationships among Nicotiana tabacum, Nicotiana sylvestrisis, Nicotiana tomentosiformis, Arabidopsis, and rice were also analyzed. The NtXTHs expression profiles analyzed by the TobEA database and qRT-PCR revealed that NtXTHs display different expression patterns in different tissues. Notably, the expression patterns of 12 NtXTHs responding to environment stresses, including salinity, alkali, heat, chilling, and plant hormones, including IAA and brassinolide, were characterized. All the results would be useful for the function study of NtXTHs during different growth cycles and stresses. PMID- 29795010 TI - Alternaria and Fusarium Fungi: Differences in Distribution and Spore Deposition in a Topographically Heterogeneous Wheat Field. AB - Fusarium spp. and Alternaria spp., two genera of filamentous fungi, are common colonizers of the wheat phyllosphere. Both can be pathogenic and produce mycotoxins that are harmful to consumers. Their in-field infection dynamics have been a focus for the development of new control strategies. We analysed the abundance on plant ears and spore deposition patterns of Fusarium spp. and Alternaria spp. in a topographically heterogeneous field. Abundances were assessed genetically, using qPCR-based techniques, and passive spore traps were installed for quantifying the spore deposition at different plant heights. Data loggers were placed to measure the differences in microclimate across the field. Results indicate different distribution and spore deposition patterns for the two fungi. Fusarium spp. spore and genetic abundances were higher in spots with a more humid and colder under-canopy microclimate. Alternaria spp. showed the opposite trend for genetic abundance, while its spore deposition was not correlated to any of the microclimatic conditions and was more uniform across the field. Our study extends the knowledge on the dispersal and in-field infection dynamics of Fusarium spp. and Alternaria spp., important for a better understanding of the epidemiology of these wheat pathogens. It also illustrates that topographically heterogeneous fields are a suitable environment for studying the ecology of phyllosphere-colonizing fungi. PMID- 29795013 TI - Mental Health Status and Associated Contributing Factors among Gay Men in China. AB - Chinese gay men are preferentially vulnerable to mental health problems because of deep-rooted, traditional social influence that overemphasizes heterosexual marriage, fertility, and filial piety. A cross-sectional survey was conducted from November to December 2017 using the Chinese version of the Symptom Checklist 90-R (SCL-90-R) to assess the status of, and factors associated with the mental health of Chinese gay men. Unadjusted associations between demographic factors and the total score of SCL-90-R were examined using t/F tests or person correlation analysis. The main factors that were most predictive of the aggregate score of SCL-90-R were identified by multiple linear regressions. A total of 367 gay men participated in this survey with an average score of SCL-90-R of 180.78 +/- 79.58. The scores of seven dimensions (OCS, INTS, DEPR, ANX, HOS, PHOA, PARI) for Chinese gay men were found to be significantly higher than the national norm (all p < 0.001). Age (B = -1.088, SE = 0.478, p = 0.023), educational level (B = 14.053, SE = 5.270, p = 0.008), and degree of coming out publicly (B = -23.750, SE = 4.690, p < 0.001) were protective factors for participants' mental health status. A gay man who is the only child in his family was more likely to obtain a higher total score of SCL-90-R in China (B = 59.321, SE = 7.798, p < 0.001). Our study reveals the worrying mental health status of Chinese gay men. Shifts in familial, governmental, and societal normas are suggested to improve the current social acceptance towards sexual minority men, as well as to reduce detrimental health effects. PMID- 29795011 TI - Cutaneous Melanoma-A Long Road from Experimental Models to Clinical Outcome: A Review. AB - Cutaneous melanoma is a complex disorder characterized by an elevated degree of heterogeneity, features that place it among the most aggressive types of cancer. Although significant progress was recorded in both the understanding of melanoma biology and genetics, and in therapeutic approaches, this malignancy still represents a major problem worldwide due to its high incidence and the lack of a curative treatment for advanced stages. This review offers a survey of the most recent information available regarding the melanoma epidemiology, etiology, and genetic profile. Also discussed was the topic of cutaneous melanoma murine models outlining the role of these models in understanding the molecular pathways involved in melanoma initiation, progression, and metastasis. PMID- 29795012 TI - Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis. AB - Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs), which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2)-binding motif of monocytes chemoattractant protein-1 (MCP-1) as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice), the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS) imaging and magnetic resonance imaging (MRI). We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis. PMID- 29795014 TI - Prenatal Perfluorooctyl Sulfonate Exposure and Alu DNA Hypomethylation in Cord Blood. AB - BACKGROUND: Perfluoroalkyl substances (PFASs) are stable and persistent in the environment, animals, and humans. PFASs can penetrate placenta and affect fetal growth. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and global methylation levels. Specific Aims and Methods: The study used the subjects from Taiwan Birth Panel birth cohort study, including all pregnant women who gave birth between July 2004 and June 2005 in four hospitals in Taipei city and New Taipei City. A total of 363 mother-infant pairs were included in the final analyses. PFOA, PFOS, PFNA, and PFUA were measured by UPLC-MS/MS in cord blood. LINE-1 and Alu repeated elements from cord blood was used to represent global DNA methylation levels. Multivariable regression models were used to adjust potential confounders. RESULTS: After controlling for potential confounders, each unit increase in the natural log-transformed PFOS exposure was associated with an adjusted OR of 1.72 (95% CI: 1.03, 2.88) for low Alu methylation level when dichotomized methylation level by medium. No significant effects between PFOA, PFNA, PFUA and methylation levels in the multivariable regression models were observed. CONCLUSIONS: Our findings suggest that prenatal PFOS exposure may be associated with low Alu methylation level. PMID- 29795015 TI - Multidisciplinary Approach for Bone Metastasis: A Review. AB - Progress in cancer treatment has improved the survival of patients with advanced stage cancers. Consequently, the clinical courses of patients are prolonged and often accompanied by morbidity due to bone metastases. Skeletal-related events (SREs), such as pathological fractures and spinal paralysis, cause impairment in activities of daily life and quality of life (QOL). To avoid serious SREs causing impairment in QOL and survival, early diagnosis and a prophylactic approach are required. It is necessary to initiate a bone management program concurrently with the initiation of cancer treatment to prevent complications of bone metastasis. In addition, the requirement of a multidisciplinary approach through a cancer board focusing on the management of bone metastases and involving a team of specialists in oncology, palliative care, radiotherapy, orthopedics, nuclear medicine, radiology, and physiatrists has been emphasized. In the cancer board, a strong focus is placed on the prevention of complications due to bone metastases and on reductions in the high morbidity, hospitalization rate, and overall costs associated with advanced-stage cancers. Recent reports suggest the usefulness of such approaches. The multidisciplinary approach through a cancer board would improve QOL and prognosis of patients, leading to new or continued systemic therapy for primary cancers. PMID- 29795016 TI - Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway. AB - Hepatic stellate cell (HSC) activation is responsible for hepatic fibrogenesis and is associated with an overexpression of transcription 3 (STAT3). Luteolin, a common dietary flavonoid with potent anti-inflammatory properties, has previously demonstrated antifibrogenic properties in HSCs but the mechanism has not been fully elucidated. Activated human and rat hepatic stellate cell lines LX-2 and HSC-T6 were used to study the effects of luteolin on HSCs. Cellular proteins were determined by western blot and immunofluorescence. Cell proliferation was assessed with Alamar Blue assay. Luteolin significantly decreased LX-2 and HSC-T6 cell viability in a time-and-dose-dependent manner, as well as decreased HSC end products alpha-smooth muscle actin (alpha-SMA), collagen I, and fibronectin. Luteolin decreased levels of total and phosphorylated STAT3, suppressed STAT3 nuclear translocation and transcriptional activity, and attenuated expression of STAT3-regulated proteins c-myc and cyclin D1. STAT3 specific inhibitors stattic and SH-4-54 demonstrated similar effects on HSC viability and alpha-SMA production. In LX-2 and HSC-T6 cells, luteolin demonstrates a potent ability to inhibit hepatic fibrogenesis via suppression of the STAT3 pathway. These results further elucidate the mechanism of luteolin as well as the effect of the STAT3 pathway on HSC activation. PMID- 29795017 TI - Detection of Intracellular Gold Nanoparticles: An Overview. AB - Photothermal therapy (PTT) takes advantage of unique properties of gold nanoparticles (AuNPs) (nanospheres, nanoshells (AuNSs), nanorods (AuNRs)) to destroy cancer cells or tumor tissues. This is made possible thanks principally to both to the so-called near-infrared biological transparency window, characterized by wavelengths falling in the range 700-1100 nm, where light has its maximum depth of penetration in tissue, and to the efficiency of cellular uptake mechanisms of AuNPs. Consequently, the possible identification of intracellular AuNPs plays a key role for estimating the effectiveness of PTT treatments. Here, we review the recognized detection techniques of such intracellular probes with a special emphasis to the exploitation of near-infrared biological transparency window. PMID- 29795018 TI - Piezoelectric Actuator with Frequency Characteristics for a Middle-Ear Implant. AB - The design and implementation of a novel piezoelectric-based actuator for an implantable middle-ear hearing aid is described in this paper. The proposed actuator has excellent low-frequency output characteristics, and can generate high output in a specific frequency band by adjusting the mechanical resonance. The actuator consists of a piezoelectric element, a miniature bellows, a cantilever membrane, a metal ring support, a ceramic tip, and titanium housing. The optimal structure of the cantilever-membrane design, which determines the frequency characteristics of the piezoelectric actuator, was derived through finite element analysis. Based on the results, the piezoelectric actuator was implemented, and its performance was verified through a cadaveric experiment. It was confirmed that the proposed actuator provides better performance than currently used actuators, in terms of frequency characteristics. PMID- 29795020 TI - Group Sparse Representation Based on Nonlocal Spatial and Local Spectral Similarity for Hyperspectral Imagery Classification. AB - Spectral-spatial classification has been widely applied for remote sensing applications, especially for hyperspectral imagery. Traditional methods mainly focus on local spatial similarity and neglect nonlocal spatial similarity. Recently, nonlocal self-similarity (NLSS) has gradually gained support since it can be used to support spatial coherence tasks. However, these methods are biased towards the direct use of spatial information as a whole, while discriminative spectral information is not well exploited. In this paper, we propose a novel method to couple both nonlocal spatial and local spectral similarity together in a single framework. In particular, the proposed approach exploits nonlocal spatial similarities by searching non-overlapped patches, whereas spectral similarity is analyzed locally within the locally discovered patches. By fusion of nonlocal and local information, we then apply group sparse representation (GSR) for classification based on a group structured prior. Experimental results on three real hyperspectral data sets demonstrate the efficiency of the proposed approach, and the improvements are significant over the methods that consider either nonlocal or local similarity. PMID- 29795019 TI - Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics. AB - Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan's Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health. PMID- 29795021 TI - Investigating the Trimethylaluminium/Water ALD Process on Mesoporous Silica by In Situ Gravimetric Monitoring. AB - A low amount of AlOx was successfully deposited on an unordered, mesoporous SiO2 powder using 1-3 ALD (Atomic Layer Deposition) cycles of trimethylaluminium and water. The process was realized in a self-built ALD setup featuring a microbalanceand a fixed particle bed. The reactor temperature was varied between 75, 120, and 200 degrees C. The self-limiting nature of the deposition was verified by in situ gravimetric monitoring for all temperatures. The coated material was further analyzed by nitrogen sorption, inductively coupled plasma optical emission spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, attenuated total reflection Fourier transformed infrared spectroscopy, and elemental analysis. The obtained mass gains correspond to average growth between 0.81-1.10 A/cycle depending on substrate temperature. In addition, the different mass gains during the half-cycles in combination with the analyzed aluminum content after one, two, and three cycles indicate a change in the preferred surface reaction of the trimethylaluminium molecule from a predominately two-ligand exchange with hydroxyl groups to more single-ligand exchange with increasing cycle number. Nitrogen sorption isotherms demonstrate (1) homogeneously coated mesopores, (2) a decrease in surface area, and (3) a reduction of the pore size. The experiment is successfully repeated in a scale-up using a ten times higher substrate batch size. PMID- 29795023 TI - Molecular Evolution in a Peptide-Vesicle System. AB - Based on a new model of a possible origin of life, we propose an efficient and stable system undergoing structural reproduction, self-optimization, and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offers vesicles as the structural environment, with the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution, and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time would not only represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence for a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to (i) reduced vesicle size, (ii) increased vesicle membrane permeability, and (iii) improved thermal vesicle stability. PMID- 29795024 TI - Early Childhood Caries-Related Knowledge, Attitude, and Practice: Discordance between Pediatricians and Dentists toward Medical Office-Based Prevention in Taiwan. AB - The aim of this study was to assess the knowledge, attitude, and practice regarding early childhood caries (ECC) prevention and implementation of medical setting-based caries prevention among pediatricians and dentists in Taiwan. Data were collected from currently practicing pediatricians and general and pediatric dentists using self-administered questionnaires. A total of 301 questionnaires were completed by the pediatricians (n = 105), general dentists (n = 117), and pediatric dentists (n = 79). The pediatric dentists obtained significantly higher knowledge and practice scores than the general dentists and pediatricians (p < 0.0001). The pediatricians' attitude score related to engaging physicians in medical office-based caries prevention was significantly higher than the attitude scores of the general and pediatric dentists (p < 0.05). A Spearman rank correlation analysis indicated a significant positive correlation between knowledge and practice among the general dentists (rs = 0.271, p < 0.01) and pediatricians (rs = 0.262, p < 0.01). The correlation between knowledge and attitude among the pediatricians was significantly positive (rs = 0.242, p < 0.05). Attitude and practice among the pediatricians were significantly positively correlated (rs = 0.271, p < 0.01). Pediatricians lacked ECC-related knowledge; however, they had a more positive attitude toward medical office-based prevention when they had a higher level of knowledge. Oral health-related education for pediatricians is necessary if such medical office-based caries prevention programs are to be implemented in Taiwan. PMID- 29795022 TI - Signaling Crosstalk of TGF-beta/ALK5 and PAR2/PAR1: A Complex Regulatory Network Controlling Fibrosis and Cancer. AB - Both signaling by transforming growth factor-beta (TGF-beta) and agonists of the G Protein-coupled receptors proteinase-activated receptor-1 (PAR1) and -2 (PAR2) have been linked to tissue fibrosis and cancer. Intriguingly, TGF-beta and PAR signaling either converge on the regulation of certain matrix genes overexpressed in these pathologies or display mutual regulation of their signaling components, which is mediated in part through sphingosine kinases and sphingosine-1-phosphate and indicative of an intimate signaling crosstalk between the two pathways. In the first part of this review, we summarize the various regulatory interactions that have been discovered so far according to the organ/tissue in which they were described. In the second part, we highlight the types of signaling crosstalk between TGF-beta on the one hand and PAR2/PAR1 on the other hand. Both ligand receptor systems interact at various levels and by several mechanisms including mutual regulation of ligand-ligand, ligand-receptor, and receptor-receptor at the transcriptional, post-transcriptional, and receptor transactivation levels. These mutual interactions between PAR2/PAR1 and TGF-beta signaling components eventually result in feed-forward loops/vicious cycles of matrix deposition and malignant traits that exacerbate fibrosis and oncogenesis, respectively. Given the crucial role of PAR2 and PAR1 in controlling TGF-beta receptor activation, signaling, TGF-beta synthesis and bioactivation, combining PAR inhibitors with TGF-beta blocking agents may turn out to be more efficient than targeting TGF beta alone in alleviating unwanted TGF-beta-dependent responses but retaining the beneficial ones. PMID- 29795027 TI - Maglev Train Signal Processing Architecture Based on Nonlinear Discrete Tracking Differentiator. AB - In a maglev train levitation system, signal processing plays an important role for the reason that some sensor signals are prone to be corrupted by noise due to the harsh installation and operation environment of sensors and some signals cannot be acquired directly via sensors. Based on these concerns, an architecture based on a new type of nonlinear second-order discrete tracking differentiator is proposed. The function of this signal processing architecture includes filtering signal noise and acquiring needed signals for levitation purposes. The proposed tracking differentiator possesses the advantages of quick convergence, no fluttering, and simple calculation. Tracking differentiator's frequency characteristics at different parameter values are studied in this paper. The performance of this new type of tracking differentiator is tested in a MATLAB simulation and this tracking-differentiator is implemented in Very-High-Speed Integrated Circuit Hardware Description Language (VHDL). In the end, experiments are conducted separately on a test board and a maglev train model. Simulation and experiment results show that the performance of this novel signal processing architecture can fulfill the real system requirement. PMID- 29795026 TI - Accurate Traffic Flow Prediction in Heterogeneous Vehicular Networks in an Intelligent Transport System Using a Supervised Non-Parametric Classifier. AB - Heterogeneous vehicular networks (HETVNETs) evolve from vehicular ad hoc networks (VANETs), which allow vehicles to always be connected so as to obtain safety services within intelligent transportation systems (ITSs). The services and data provided by HETVNETs should be neither interrupted nor delayed. Therefore, Quality of Service (QoS) improvement of HETVNETs is one of the topics attracting the attention of researchers and the manufacturing community. Several methodologies and frameworks have been devised by researchers to address QoS prediction service issues. In this paper, to improve QoS, we evaluate various traffic characteristics of HETVNETs and propose a new supervised learning model to capture knowledge on all possible traffic patterns. This model is a refinement of support vector machine (SVM) kernels with a radial basis function (RBF). The proposed model produces better results than SVMs, and outperforms other prediction methods used in a traffic context, as it has lower computational complexity and higher prediction accuracy. PMID- 29795025 TI - Enhanced Anti-Mycobacterium tuberculosis Immunity over Time with Combined Drug and Immunotherapy Treatment. AB - It is estimated that one third of the world's population is infected with Mycobacterium tuberculosis (Mtb). This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)), in combination with rifampicin, isoniazid, and pyrazinamide (RHZ) drug treatment. We assessed the host inflammatory immune responses and lung pathology 7-22 weeks post infection, and determined the therapeutic efficacy of combined treatment by enumeration of the bacterial load and survival in the SWR/J mouse model. We show that drug treatment alone, or with immunotherapy, tempered the inflammatory responses measured in brochoalveolar lavage fluid and plasma compared to untreated cohorts. RHZ combined with therapeutic immunizations significantly enhanced TH1-type cytokine responses in the lung over time, corresponding to decreased pulmonary pathology evidenced by a significant decrease in the percentage of lung lesions and destructive lung inflammation. These data suggest that bacterial burden assessment alone may miss important correlates of lung architecture that directly contribute to therapeutic vaccine efficacy in the preclinical mouse model. We also confirmed our previous finding that in combination with antibiotics therapeutic immunizations provide an additive survival advantage. Moreover, therapeutic immunizations with ID93/GLA-SE induced differential T cell immune responses over the course of infection that correlated with periods of enhanced bacterial control over that of drug treatment alone. Here we advance the immunotherapy model and investigate reliable correlates of protection and Mtb control. PMID- 29795029 TI - High Temperature Flow Behavior of Ultra-Strong Nanoporous Au assessed by Spherical Nanoindentation. AB - Nanoporous metals have attracted attention in various research fields in the past years since their unique microstructures make them favorable for catalytic, sensory or microelectronic applications. Moreover, the refinement of the ligaments down to the nanoscale leads to an exceptionally high strength. To guarantee a smooth implementation of nanoporous metals into modern devices their thermo-mechanical behavior must be properly understood. Within this study the mechanical flow properties of nanoporous Au were investigated at elevated temperatures up to 300 degrees C. In contrast to the conventional synthesis by dealloying of AuAg precursors, the present foam was fabricated via severe plastic deformation of an AuFe nanocomposite and subsequent selective etching of iron, resulting in Au ligaments consisting of nanocrystalline grains, while remaining Fe impurities excessively stabilize the microstructure. A recently developed spherical nanoindentation protocol was used to extract the stress-strain curves of nanoporous Au. A tremendous increase of yield strength due to ligament and grain refinement was observed, which is largely maintained at high temperatures. Reviewing literature will evidence that the combined nanocrystalline and nanoporous structure leads to remarkable mechanical properties. Furthermore, comparison to a previous Berkovich nanoindentation study outlines the conformity of different indentation techniques. PMID- 29795028 TI - Direct Self-Injurious Behavior (D-SIB) and Life Events among Vocational School and High School Students. AB - Although several studies have recently assessed direct self-injurious behavior (D SIB) among adolescents, it is still understudied in adolescents attending vocational schools: an educational setting generally associated with lower socioeconomic status. After extending the "Saving and Empowering Young Lives in Europe" (SEYLE) project to a vocational school population, we examined their D SIB and life event characteristics compared to the high school population. SEYLE's Hungarian randomly selected high school sample (N = 995) was completed with a randomly selected vocational school sample (N = 140) in Budapest, Hungary. Participants aged 14-17 years completed the SEYLE project's self-administered questionnaires. D-SIB lifetime prevalence was significantly higher (29.4%) in the vocational school group compared to the high school group (17.2%) (Chi2(1) = 12.231, p< 0.001). D-SIB was associated with suicidal ideation in the vocational school group. Different life events were more frequent in the high school than in the vocational school group, and associations between D-SIB and life events differed in the vocational school group compared to the high school group. In conclusion, vocational school students are a vulnerable population with a higher prevalence of D-SIB compared to high school students. Life events and their association with D-SIB also differ in vocational school students compared to high school students. Taking all these into account might contribute to prevention/intervention designed for this population. PMID- 29795030 TI - Digital Self-Interference Cancellation for Asynchronous In-Band Full-Duplex Underwater Acoustic Communication. AB - To improve the throughput of underwater acoustic (UWA) networking, the In-band full-duplex (IBFD) communication is one of the most vital pieces of research. The major drawback of IBFD-UWA communication is Self-Interference (SI). This paper presents a digital SI cancellation algorithm for asynchronous IBFD-UWA communication system. We focus on two issues: one is asynchronous communication dissimilar to IBFD radio communication, the other is nonlinear distortion caused by power amplifier (PA). First, we discuss asynchronous IBFD-UWA signal model with the nonlinear distortion of PA. Then, we design a scheme for asynchronous IBFD-UWA communication utilizing the non-overlapping region between SI and intended signal to estimate the nonlinear SI channel. To cancel the nonlinear distortion caused by PA, we propose an Over-Parameterization based Recursive Least Squares (RLS) algorithm (OPRLS) to estimate the nonlinear SI channel. Furthermore, we present the OPRLS with a sparse constraint to estimate the SI channel, which reduces the requirement of the length of the non-overlapping region. Finally, we verify our concept through simulation and the pool experiment. Results demonstrate that the proposed digital SI cancellation scheme can cancel SI efficiently. PMID- 29795031 TI - Towards an Online Seizure Advisory System-An Adaptive Seizure Prediction Framework Using Active Learning Heuristics. AB - In the last decade, seizure prediction systems have gained a lot of attention because of their enormous potential to largely improve the quality-of-life of the epileptic patients. The accuracy of the prediction algorithms to detect seizure in real-world applications is largely limited because the brain signals are inherently uncertain and affected by various factors, such as environment, age, drug intake, etc., in addition to the internal artefacts that occur during the process of recording the brain signals. To deal with such ambiguity, researchers transitionally use active learning, which selects the ambiguous data to be annotated by an expert and updates the classification model dynamically. However, selecting the particular data from a pool of large ambiguous datasets to be labelled by an expert is still a challenging problem. In this paper, we propose an active learning-based prediction framework that aims to improve the accuracy of the prediction with a minimum number of labelled data. The core technique of our framework is employing the Bernoulli-Gaussian Mixture model (BGMM) to determine the feature samples that have the most ambiguity to be annotated by an expert. By doing so, our approach facilitates expert intervention as well as increasing medical reliability. We evaluate seven different classifiers in terms of the classification time and memory required. An active learning framework built on top of the best performing classifier is evaluated in terms of required annotation effort to achieve a high level of prediction accuracy. The results show that our approach can achieve the same accuracy as a Support Vector Machine (SVM) classifier using only 20 % of the labelled data and also improve the prediction accuracy even under the noisy condition. PMID- 29795032 TI - Influence of Different Coupling Modes on the Robustness of Smart Grid under Targeted Attack. AB - Many previous works only focused on the cascading failure of global coupling of one-to-one structures in interdependent networks, but the local coupling of dual coupling structures has rarely been studied due to its complex structure. This will result in a serious consequence that many conclusions of the one-to-one structure may be incorrect in the dual coupling network and do not apply to the smart grid. Therefore, it is very necessary to subdivide the dual coupling link into a top-down coupling link and a bottom-up coupling link in order to study their influence on network robustness by combining with different coupling modes. Additionally, the power flow of the power grid can cause the load of a failed node to be allocated to its neighboring nodes and trigger a new round of load distribution when the load of these nodes exceeds their capacity. This means that the robustness of smart grids may be affected by four factors, i.e., load redistribution, local coupling, dual coupling link and coupling mode; however, the research on the influence of those factors on the network robustness is missing. In this paper, firstly, we construct the smart grid as a two-layer network with a dual coupling link and divide the power grid and communication network into many subnets based on the geographical location of their nodes. Secondly, we define node importance ( N I ) as an evaluation index to access the impact of nodes on the cyber or physical network and propose three types of coupling modes based on N I of nodes in the cyber and physical subnets, i.e., Assortative Coupling in Subnets (ACIS), Disassortative Coupling in Subnets (DCIS), and Random Coupling in Subnets (RCIS). Thirdly, a cascading failure model is proposed for studying the effect of local coupling of dual coupling link in combination with ACIS, DCIS, and RCIS on the robustness of the smart grid against a targeted attack, and the survival rate of functional nodes is used to assess the robustness of the smart grid. Finally, we use the IEEE 118-Bus System and the Italian High-Voltage Electrical Transmission Network to verify our model and obtain the same conclusions: (I) DCIS applied to the top-down coupling link is better able to enhance the robustness of the smart grid against a targeted attack than RCIS or ACIS, (II) ACIS applied to a bottom-up coupling link is better able to enhance the robustness of the smart grid against a targeted attack than RCIS or DCIS, and (III) the robustness of the smart grid can be improved by increasing the tolerance alpha . This paper provides some guidelines for slowing down the speed of the cascading failures in the design of architecture and optimization of interdependent networks, such as a top-down link with DCIS, a bottom-up link with ACIS, and an increased tolerance alpha . PMID- 29795034 TI - Geometric Positioning Accuracy Improvement of ZY-3 Satellite Imagery Based on Statistical Learning Theory. AB - With the increasing demand for high-resolution remote sensing images for mapping and monitoring the Earth's environment, geometric positioning accuracy improvement plays a significant role in the image preprocessing step. Based on the statistical learning theory, we propose a new method to improve the geometric positioning accuracy without ground control points (GCPs). Multi-temporal images from the ZY-3 satellite are tested and the bias-compensated rational function model (RFM) is applied as the block adjustment model in our experiment. An easy and stable weight strategy and the fast iterative shrinkage-thresholding (FIST) algorithm which is widely used in the field of compressive sensing are improved and utilized to define the normal equation matrix and solve it. Then, the residual errors after traditional block adjustment are acquired and tested with the newly proposed inherent error compensation model based on statistical learning theory. The final results indicate that the geometric positioning accuracy of ZY-3 satellite imagery can be improved greatly with our proposed method. PMID- 29795033 TI - K15 Protein of Kaposi's Sarcoma Herpesviruses Increases Endothelial Cell Proliferation and Migration through Store-Operated Calcium Entry. AB - Kaposi's sarcoma (KS) is a tumor of the vascular endothelium that is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). K15 of KSHV is a specific gene encoding a transmembrane protein. Two highly different forms of K15, the predominant (K15P) and minor (K15M) have been identified in different KSHV strains. In genomic locations and protein topology, two K15 alleles resemble the latent membrane protein (LMP) 1 and LMP2A of Epstein-Barr virus. Both K15 proteins have motifs similar to those found in LMP1 and LMP2A. K15 therefore seems to be a hybrid of a distant evolutionary relative of LMP1 and LMP2A. Ca2+ is a second messenger and participates in numerous activities in cells, like proliferation, migration and metastasis. It has been found previously that LMP1 increased Ca2+ influx through store-operated calcium channels and blockade of LMP1 reduced store-operated Ca2+ entry (SOCE). LMP2A has similar activity. So we sought to determine whether K15 had similar activity. We showed that K15P induced Ca2+ influx and enhanced expression of Orail1, which is a vital protein in SOCE, and overexpression of K15P improved cell motility. Mutant K15P did not show these activities in HEK-293T and EA.hy 926 cells. Our results showed that K15P increased cell proliferation and migration though SOCE and established a novel mechanism for the development of KS and KSHV-associated diseases. PMID- 29795035 TI - Outlier-Detection Methodology for Structural Identification Using Sparse Static Measurements. AB - The aim of structural identification is to provide accurate knowledge of the behaviour of existing structures. In most situations, finite-element models are updated using behaviour measurements and field observations. Error-domain model falsification (EDMF) is a multi-model approach that compares finite-element model predictions with sensor measurements while taking into account epistemic and stochastic uncertainties-including the systematic bias that is inherent in the assumptions behind structural models. Compared with alternative model-updating strategies such as residual minimization and traditional Bayesian methodologies, EDMF is easy-to-use for practising engineers and does not require precise knowledge of values for uncertainty correlations. However, wrong parameter identification and flawed extrapolation may result when undetected outliers occur in the dataset. Moreover, when datasets consist of a limited number of static measurements rather than continuous monitoring data, the existing signal processing and statistics-based algorithms provide little support for outlier detection. This paper introduces a new model-population methodology for outlier detection that is based on the expected performance of the as-designed sensor network. Thus, suspicious measurements are identified even when few measurements, collected with a range of sensors, are available. The structural identification of a full-scale bridge in Exeter (UK) is used to demonstrate the applicability of the proposed methodology and to compare its performance with existing algorithms. The results show that outliers, capable of compromising EDMF accuracy, are detected. Moreover, a metric that separates the impact of powerful sensors from the effects of measurement outliers have been included in the framework. Finally, the impact of outlier occurrence on parameter identification and model extrapolation (for example, reserve capacity assessment) is evaluated. PMID- 29795036 TI - Experimental Methods for Studying Cellular Heme Signaling. AB - The study of heme is important to our understanding of cellular bioenergetics, especially in cancer cells. The function of heme as a prosthetic group in proteins such as cytochromes is now well-documented. Less is known, however, about its role as a regulator of metabolic and energetic pathways. This is due in part to some inherent difficulties in studying heme. Due to its slightly amphiphilic nature, heme is a "sticky" molecule which can easily bind non specifically to proteins. In addition, heme tends to dimerize, oxidize, and aggregate in purely aqueous solutions; therefore, there are constraints on buffer composition and concentrations. Despite these difficulties, our knowledge of heme's regulatory role continues to grow. This review sums up the latest methods used to study reversible heme binding. Heme-regulated proteins will also be reviewed, as well as a system for imaging the cellular localization of heme. PMID- 29795037 TI - Oxidation Resistance and Wetting Behavior of MgO-C Refractories: Effect of Carbon Content. AB - Abstract: Various carbon contents in the MgO-C refractory were studied with respect to the oxidation resistance and the wetting behavior with slag. The bulk density, apparent porosity, cold crushing strength, oxidation rate, and mass loss rate of the fired MgO-C refractories with various carbon contents were measured and compared. The wetting and penetration behavior of the cured MgO-C refractory with the molten slag were observed in-situ. The contact angle and the shape parameters of molten slag, including the apparent radius, height, and volume were compared. The results showed that the regenerated MgO effectively restrained the carbon oxidation in the MgO-C refractory, which was more evident at the low carbon content refractory. The contact angle between the MgO-C refractory and the molten slag increased as the carbon content increased. The increased contact angle decreased the penetration of the molten slag. PMID- 29795038 TI - LightDenseYOLO: A Fast and Accurate Marker Tracker for Autonomous UAV Landing by Visible Light Camera Sensor on Drone. AB - Autonomous landing of an unmanned aerial vehicle or a drone is a challenging problem for the robotics research community. Previous researchers have attempted to solve this problem by combining multiple sensors such as global positioning system (GPS) receivers, inertial measurement unit, and multiple camera systems. Although these approaches successfully estimate an unmanned aerial vehicle location during landing, many calibration processes are required to achieve good detection accuracy. In addition, cases where drones operate in heterogeneous areas with no GPS signal should be considered. To overcome these problems, we determined how to safely land a drone in a GPS-denied environment using our remote-marker-based tracking algorithm based on a single visible-light-camera sensor. Instead of using hand-crafted features, our algorithm includes a convolutional neural network named lightDenseYOLO to extract trained features from an input image to predict a marker's location by visible light camera sensor on drone. Experimental results show that our method significantly outperforms state-of-the-art object trackers both using and not using convolutional neural network in terms of both accuracy and processing time. PMID- 29795039 TI - Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors. AB - Carbonic anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life, classified into seven genetically different families (alpha-theta). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) have been used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors. PMID- 29795040 TI - Recent Insights into Mucinous Ovarian Carcinoma. AB - Ovarian mucinous tumors represent a group of rare neoplasms with a still undefined cell of origin but with an apparent progression from benign to borderline to carcinoma. Even though these tumors are different from the other histological subtypes of epithelial ovarian neoplasms, they are still treated with a similar chemotherapeutic approach. Here, we review its pathogenesis, molecular alterations, (differential) diagnosis, clinical presentation and current treatment, and how recent molecular and biological information on this tumor might lead to better and more specific clinical management of patients with mucinous ovarian carcinoma. PMID- 29795042 TI - Electrical Resistance Tomography for Visualization of Moving Objects Using a Spatiotemporal Total Variation Regularization Algorithm. AB - Electrical resistance tomography (ERT) has been considered as a data collection and image reconstruction method in many multi-phase flow application areas due to its advantages of high speed, low cost and being non-invasive. In order to improve the quality of the reconstructed images, the Total Variation algorithm attracts abundant attention due to its ability to solve large piecewise and discontinuous conductivity distributions. In industrial processing tomography (IPT), techniques such as ERT have been used to extract important flow measurement information. For a moving object inside a pipe, a velocity profile can be calculated from the cross correlation between signals generated from ERT sensors. Many previous studies have used two sets of 2D ERT measurements based on pixel-pixel cross correlation, which requires two ERT systems. In this paper, a method for carrying out flow velocity measurement using a single ERT system is proposed. A novel spatiotemporal total variation regularization approach is utilised to exploit sparsity both in space and time in 4D, and a voxel-voxel cross correlation method is adopted for measurement of flow profile. Result shows that the velocity profile can be calculated with a single ERT system and that the volume fraction and movement can be monitored using the proposed method. Both semi-dynamic experimental and static simulation studies verify the suitability of the proposed method. For in plane velocity profile, a 3D image based on temporal 2D images produces velocity profile with accuracy of less than 1% error and a 4D image for 3D velocity profiling shows an error of 4%. PMID- 29795041 TI - Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFV600E-Specific Inhibitor). AB - Malignant melanoma is the most aggressive form of skin cancer and has a very low survival rate. Over 50% of melanomas harbor various BRAF mutations with the most common being the V600E. BRAFV600E mutation that causes constitutive activation of the MAPK pathway leading to drug-, immune-resistance, apoptosis evasion, proliferation, survival, and metastasis of melanomas. The ATP competitive BRAFV600E selective inhibitor, vemurafenib, has shown dramatic success in clinical trials; promoting tumor regression and an increase in overall survival of patients with metastatic melanoma. Regrettably, vemurafenib-resistance develops over an average of six months, which renders melanomas resistant to other therapeutic strategies. Elucidation of the underlying mechanism(s) of acquisition of vemurafenib-resistance and design of novel approaches to override resistance is the subject of intense clinical and basic research. In this review, we summarize recent developments in therapeutic approaches and clinical investigations on melanomas with BRAFV600E mutation to establish a new platform for the treatment of melanoma. PMID- 29795043 TI - Na+-Dependent High-Affinity Nitrate, Phosphate and Amino Acids Transport in Leaf Cells of the Seagrass Posidonia oceanica (L.) Delile. AB - Posidonia oceanica (L.) Delile is a seagrass, the only group of vascular plants to colonize the marine environment. Seawater is an extreme yet stable environment characterized by high salinity, alkaline pH and low availability of essential nutrients, such as nitrate and phosphate. Classical depletion experiments, membrane potential and cytosolic sodium measurements were used to characterize the high-affinity NO3-, Pi and amino acids uptake mechanisms in this species. Net uptake rates of both NO3- and Pi were reduced by more than 70% in the absence of Na+. Micromolar concentrations of NO3- depolarized mesophyll leaf cells plasma membrane. Depolarizations showed saturation kinetics (Km = 8.7 +/- 1 MUM NO3-), which were not observed in the absence of Na+. NO3- induced depolarizations at increasing Na+ also showed saturation kinetics (Km = 7.2 +/- 2 mM Na+). Cytosolic Na+ measured in P. oceanica leaf cells (17 +/- 2 mM Na+) increased by 0.4 +/- 0.2 mM Na+ upon the addition of 100 MUM NO3-. Na+-dependence was also observed for high-affinity l-ala and l-cys uptake and high-affinity Pi transport. All together, these results strongly suggest that NO3-, amino acids and Pi uptake in P. oceanica leaf cells are mediated by high-affinity Na+-dependent transport systems. This mechanism seems to be a key step in the process of adaptation of seagrasses to the marine environment. PMID- 29795045 TI - The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior. AB - Although important progress has been achieved in understanding the catalytic mechanism of Carbonic Anhydrases, a detailed picture of all factors influencing the catalytic efficiency of the various human isoforms is still missing. In this paper we report a detailed structural study and theoretical pKa calculations on a hCA VII variant. The obtained data were compared with those already known for another thoroughly investigated cytosolic isoform, hCA II. Our structural studies show that in hCA VII the network of ordered water molecules, which connects the zinc bound solvent molecule to the proton shuttle His64, is altered compared to hCA II, causing a reduction of the catalytic efficiency. Theoretical calculations suggest that changes in solvent network are related to the difference in pKa of the proton shuttle in the two enzymes. The residue that plays a major role in determining the diverse pKa values of the proton shuttle is the one in position four, namely His for hCA II and Gly for hCA VII. This residue is located on the protein surface, outside of the active site cavity. These findings are in agreement with our previous studies that highlighted the importance of histidines on the protein surface of hCA II (among which His4) as crucial residues for the high catalytic efficiency of this isoform. PMID- 29795046 TI - Spectral Kurtosis Entropy and Weighted SaE-ELM for Bogie Fault Diagnosis under Variable Conditions. AB - Bogies are crucial for the safe operation of rail transit systems and usually work under uncertain and variable operating conditions. However, the diagnosis of bogie faults under variable conditions has barely been discussed until now. Thus, it is valuable to develop effective methods to deal with variable conditions. Besides, considering that the normal data for training are much more than the faulty data in practice, there is another problem in that only a small amount of data is available that includes faults. Concerning these issues, this paper proposes two new algorithms: (1) A novel feature parameter named spectral kurtosis entropy (SKE) is proposed based on the protrugram. The SKE not only avoids the manual post-processing of the protrugram but also has strong robustness to the operating conditions and parameter configurations, which have been validated by a simulation experiment in this paper. In this paper, the SKE, in conjunction with variational mode decomposition (VMD), is employed for feature extraction under variable conditions. (2) A new learning algorithm named weighted self-adaptive evolutionary extreme learning machine (WSaE-ELM) is proposed. WSaE ELM gives each sample an extra sample weight to rebalance the training data and optimizes these weights along with the parameters of hidden neurons by means of the self-adaptive differential evolution algorithm. Finally, the hybrid method based on VMD, SKE, and WSaE-ELM is verified by using the vibration signals gathered from real bogies with speed variations. It is demonstrated that the proposed method of bogie fault diagnosis outperforms the conventional methods by up to 4.42% and 6.22%, respectively, in percentages of accuracy under variable conditions. PMID- 29795044 TI - A Gelatin Hydrogel-Containing Nano-Organic PEI-Ppy with a Photothermal Responsive Effect for Tissue Engineering Applications. AB - The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)-Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin-PEI-Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR triggerable property that provides local hyperthermic temperature by PEI-Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications. PMID- 29795048 TI - The Conversion of 5,5'-Bi(1,2,3-dithiazolylidenes) into Isothiazolo[5,4 d]isothiazoles. AB - Thermolysis of 4,4'-dichloro-, 4,4'-diaryl-, and 4,4'-di(thien-2-yl)-5,5' bi(1,2,3-dithiazol-ylidenes) affords the respective 3,6-dichloro-, 3,6-diaryl- and 3,6-di(thien-2-yl)isothiazolo[5,4-d]-isothiazoles in low to high yields. The transformation of the 4,4'-diaryl- and 4,4'-di(thien-2-yl)-5,5'-bi(1,2,3 dithiazolylidenes) occurs at lower temperatures in the presence of the thiophiles triphenylphosphine or tetraethylammonium iodide. Optimized reaction conditions and a mechanistic rationale for the thiophile-mediated ring transformation are presented. PMID- 29795047 TI - Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro. AB - The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection. PMID- 29795049 TI - Parental Migration and Left-Behind Children's Depressive Symptoms: Estimation Based on a Nationally-Representative Panel Dataset. AB - China's rapid urbanization in the past several decades have been accompanied by rural labor migration. An important question that has emerged is whether rural labor migration has a positive or negative impact on the depressive symptoms of children left behind in the countryside by their migrating parents. This paper uses a nationally representative panel dataset to investigate whether parental migration impacts the prevalence of depressive symptoms among left-behind children in China. Using DID and PSM-DID methods, our results show that parental migration significantly increases the depression scores of 10 and 11-year-old children by 2 points using the CES-D depression scale. Furthermore, we also find that the negative effect of decreased parental care is stronger than the positive effect of increased income in terms of determining the depressive symptoms status of children in rural China. PMID- 29795051 TI - Beyond the Edge of Hypomethylating Agents: Novel Combination Strategies for Older Adults with Advanced MDS and AML. AB - Higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) of the elderly exhibit several commonalities, including first line treatment with hypomethylating agents (HMA) like azacitidine (AZA) or decitabine (DAC). Until today, response to treatment occurs in less than 50 percent of patients, and is often short-lived. Moreover, patients failing HMA have a dismal prognosis. Current developments include combinations of HMA with novel drugs targeting epigenetic or immunomodulatory pathways. Other efforts focus on the prevention of resistance to HMA using checkpoint inhibitors to enhance immune attack. This review focuses on recent advances in the field of HMA-based front-line therapies in elderly patients with myeloid diseases. PMID- 29795050 TI - Transitions from Single- to Multi-Locus Processes during Speciation with Gene Flow. AB - During speciation-with-gene-flow, a transition from single-locus to multi-locus processes can occur, as strong coupling of multiple loci creates a barrier to gene flow. Testing predictions about such transitions with empirical data requires building upon past theoretical work and the continued development of quantitative approaches. We simulated genomes under several evolutionary scenarios of gene flow and divergent selection, extending previous work with the additions of neutral sites and coupling statistics. We used these simulations to investigate, in a preliminary way, if and how selected and neutral sites differ in the conditions they require for transitions during speciation. For the parameter combinations we explored, as the per-locus strength of selection grew and/or migration decreased, it became easier for selected sites to show divergence-and thus to rise in linkage disequilibrium (LD) with each other as a statistical consequence-farther in advance of the conditions under which neutral sites could diverge. Indeed, even very low rates of effective gene flow were sufficient to prevent differentiation at neutral sites. However, once strong enough, coupling among selected sites eventually reduced gene flow at neutral sites as well. To explore whether similar transitions might be detectable in empirical data, we used published genome resequencing data from three taxa of Heliconius butterflies. We found that fixation index ( F S T ) outliers and allele-frequency outliers exhibited stronger patterns of within-deme LD than the genomic background, as expected. The statistical characteristics of within-deme LD-likely indicative of the strength of coupling of barrier loci-varied between chromosomes and taxonomic comparisons. Qualitatively, the patterns we observed in the empirical data and in our simulations suggest that selection drives rapid genome-wide transitions to multi-locus coupling, illustrating how divergence and gene flow interact along the speciation continuum. PMID- 29795052 TI - Association between Dietary Mineral Intake and Chronic Kidney Disease: The Health Examinees (HEXA) Study. AB - Few studies have explored the association between mineral intake and chronic kidney disease (CKD). A cross-sectional analysis investigated the association between mineral intake (calcium, phosphorus, sodium, potassium, iron, and zinc) and CKD using the Health Examinee (HEXA) cohort of the Korean Genome and Epidemiologic Study (KoGES). For 159,711 participants, mineral intake was assessed by a food frequency questionnaire. CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. Dietary intake of each mineral was divided into quartiles and the quartile including recommended dietary allowance (RDA) or adequate intake (AI) of each mineral was used as a reference. We assessed the association between the quartile of mineral intakes and CKD using polytomous logistic regression models. The lowest quartiles of phosphorus (<=663.68 mg/day, odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.25-2.15), potassium (<=1567.53 mg/day, OR = 1.87, 95% CI: 1.27-2.75), iron (<=6.93 mg/day, OR = 1.53, 95% CI: 1.17-2.01), and zinc (<=5.86 mg/day, OR = 1.52, 95% CI: 1.02-2.26) were associated with higher odds for advanced CKD compared with the references. The present study suggests that an inadequate intake of some minerals may be associated with CKD occurrence in the general population. Due to the reverse causation issue in this cross-sectional study design, further longitudinal prospective studies are needed in order to prove the results. PMID- 29795054 TI - Marital Status and Survival of Patients with Hormone Receptor-Positive Male Breast Cancer: A Surveillance, Epidemiology, and End Results (SEER) Population Based Study. AB - BACKGROUND Although marital status has been reported as a prognostic factor in different cancer types, its prognostic effect on hormone receptor (HR) positive male breast cancer (MBC) is unclear. The objective of the present analysis was to assess the effects of marital status on survival in patients with HR positive MBC. MATERIAL AND METHODS Patients diagnosed with HR positive MBC from 1990 to 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to identify the effects of marital status on cancer-specific survival (CSS) and overall survival (OS). RESULTS A total of 3612 cases were identified in this study. Married patients had better 5-year CSS and 5-year OS than unmarried men. In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS and OS, independent of age, race, grade, stage, PR status, HER2 status, and surgery. Subgroup survival analysis according to different ER/PR status showed that married patients had beneficial CSS results only in ER+/PR+ subtype, and CSS in the married and unmarried groups did not significantly differ by TNM stage. The results were further confirmed in the 1: 1 matched group. CONCLUSIONS Marital status was an important prognostic factor for survival in patients with HR positive MBC. Unmarried patients are at greater risk of death compared with married groups. The survival benefit for married patients remained even after adjustment, which indicates the importance of spousal support in MBC. PMID- 29795055 TI - Role of Immuno-Polymerase Chain Reaction (I-PCR) in Resolving Diagnostic Dilemma Between Tuberculoma and Neurocysticercosis: A Case Report. AB - BACKGROUND Tuberculoma and neurocysticercosis (NCC) often show similar clinical and neuroimaging features. Differential diagnosis of these 2 diseases is imperative, as tuberculoma is an active infection that requires immediate anti tubercular therapy (ATT). CASE REPORT We present the case of a 17-year-old Indian girl with fever, severe headache, and right 6th cranial nerve palsy. Brain magnetic resonance imaging (MRI) showed multiple tiny ring-enhancing lesions in bilateral cerebral parenchyma with mild perilesional edema, which were initially thought to be NCC, but subsequently were diagnosed as brain tuberculomas. Based on clinical findings, mildly increased choline/creatine ratio (1.35) with slight prominent lipid lactate peak and absence of alanine, succinate peak by magnetic resonance spectroscopy (MRS), and the detection of Mycobacterium tuberculosis (Mtb)-specific early-secreted antigenic target-6 (ESAT-6, Rv3875) protein from the cerebrospinal fluid (CSF) by indirect ELISA, as well as indirect immuno-PCR (I-PCR) assay, diagnosis of brain tuberculomas associated with tuberculous meningitis (TBM) was confirmed, which was followed by ATT. The patient responded well and the symptoms resolved. CONCLUSIONS In this case, multiple ring-enhancing lesions of the brain by MRI were diagnosed as tuberculomas associated with TBM by MRS and indirect ELISA/I-PCR method, thus resolving the diagnostic dilemma. PMID- 29795056 TI - Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing. AB - BACKGROUND Spinal tuberculosis (STB) is the main cause of bone and joint tuberculosis. This study aimed to screen and analyze the susceptibility genes for STB using whole-exome sequencing (WES). MATERIAL AND METHODS All exon regions of peripheral blood DNA from 6 STB patients were captured and sequenced using WES and the sequencing data were analyzed by modern bioinformatics methods to identify disease-causing mutations. Sanger sequencing was then used to validate the mutation sites in normal controls (207) and STB patients (193). The mRNA expression of the mutant gene and the serum levels of IL-6 and TNF-alpha were detected using qPCR or ELISA assay, respectively. RESULTS A nonsynonymous single nucleotide polymorphism (SNP) in the gene HLA-DQA1 (rs796778515, c.592delCinsG, CAG to GAG, p.Q198E) was identified and further validated by Sanger sequencing. The percentage of the 3 genotypes C/C, C/G and G/G in STB patients and normal controls were 37.3%, 32.1%, and 30.6% and 47.8%, 33.8%, and 18.4%, respectively. Furthermore, the C>G mutation was significantly associated with the occurrence of STB. In addition, the levels of HLA-DQA1 mRNA were significantly lower in blood cells from STB patients compared with normal controls, while the serum levels of IL-6 and TNF-alpha were significantly higher. CONCLUSIONS The C>G mutation in the HLA-DQA1 gene was associated with the occurrence of STB. This variation may result in the decreased level of HLA-DQA1 mRNA and increased serum levels of IL-6 and TNF-alpha, which finally led the STB susceptibility. PMID- 29795058 TI - Delayed Serotonin Syndrome in the Setting of a Mixed Fluoxetine and Serotonin Antagonist Overdose. AB - BACKGROUND Serotonin syndrome is a condition characterized predominantly by neuromuscular symptoms and altered thermoregulation in response to serotonergic overtone. Treatment is focused on withdrawal of serotonergic agents, which leads to resolution in the majority of cases. In the setting of serotonergic overdose, the onset of serotonin syndrome is usually within 4 to 13 h. Here, we report a case of delayed-onset serotonin syndrome in a patient who ingested a mixture of longer-acting serotonin agonists with serotonin antagonists. CASE REPORT A 24 year-old male was transferred to our medical intensive care unit with hypotension and altered mental status after an overdose of fluoxetine, cyproheptadine, trazodone, olanzapine, risperidone, and bupropion. After approximately 72 h, the patient developed symptoms of fever, lower leg clonus, hyperreflexia, and agitation. He was diagnosed with delayed-onset serotonin syndrome, which responded well to re-administration of cyproheptadine, leading to resolution of symptoms by day 5 of his stay. CONCLUSIONS In this present case, our patient presented with the longest reported delay in the onset of serotonin syndrome after intentional ingestion. This was likely secondary to co-ingestion of long acting serotonin agonists with protective shorter-acting serotonin antagonists (cyproheptadine and olanzapine). Clinicians should consider delayed-onset serotonin syndrome when patients ingest longer-acting serotonergic agents with serotonin antagonists. PMID- 29795061 TI - Endoscopic resection: a pathologist's point of view! What affects specimen quality? AB - Various methods, indications and technical devices for endoscopic resections are available. Degrees of artificial changes that may hamper the histopathological diagnosis vary from method to method and from gastroenterologist to gastroenterologist. Indications for endoscopic resections are nowadays seen wider as compared to ten years ago. This leads to a situation that more institutions and gastroenterologists offer these new methods for their patients. Indirectly, pathology is involved also since most of these specimens will not be sent to one dedicated experienced pathologist anymore but to many local pathologists that may not see enough specimens to properly train their skills in a routine setting. The same is true for the gastroenterologists outside the larger centers that are already applying these methods for a longer time. The quality of the specimen is very central for a correct diagnosis and it already starts in the endoscopy suite that the quality can be hampered. The following article provides hints on how to keep the quality of such a specimen as high as possible for gastroenterologists and pathologists and gives some diagnostic advice for pathologists as well. PMID- 29795057 TI - Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis. AB - BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 MUM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases. RESULTS A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets. CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC. PMID- 29795060 TI - Robot-assisted liver surgery in a general surgery unit with a "Referral Centre Hub&Spoke Learning Program". Early outcomes after our first 70 consecutive patients. AB - BACKGROUND: The aim of this study was to evaluate safety, feasibility and short term outcomes of our first 70 consecutive patients treated by robotic-assisted liver resection after a reversal proctoring between a high HPB volume centre and our well-trained center in minimally invasive General Surgery. Six surgeons were involved in this Hub&Spoke learning program. METHODS: From September 2012 to December 2016, 70 patients underwent robotic-assisted liver resections (RALR). We treated 18 patients affected by colorectal and gastric cancer with synchronous liver lesions suspected for metastases in a one-stage robotic-assisted procedure. For the first 20 procedures we had a tutor in the operatory room, who was present also in the next most difficult procedures. RESULTS: The 30- and 90-day mortality rate was zero with an overall morbidity rate of 10.1%. Associated surgical procedures were performed in about 65,7% of patients. The observed conversion rate was 10%. The results of the first 20 cases were similar to the next 50 showing a shortned learning curve. CONCLUSIONS: Minimally invasive robot-assisted liver resection is a safe technique; it allows overcoming many limits of conventional laparoscopy. This innovative, time-enduring Hub&Spoke may allow patients to undergo a proper standard of care also for complex surgical procedures, without the need of reaching referral centres. PMID- 29795062 TI - Laparoscopic treatment of rectal cancer and lateral pelvic lymph node dissection: are they obsolete? AB - Laparoscopic surgery for rectal cancer offers favorable short-term results without compromising long term oncological outcomes so far, according to the data from major trials. For this reason, it is currently considered as a standard option for rectal cancer surgery. The learning curve of laparoscopic rectal cancer surgery is generally longer compared to colon cancer. Appropriate standardization and training of laparoscopic rectal cancer surgery is required. Several RCTs suggested the potential negative effect on quality of resected specimen, which can increase local recurrence. The long-term outcomes - especially local recurrence rate - of these RCTs are awaited. Lateral pelvic lymph node dissection (LPLND) has a certain effect of reducing local recurrence of rectal cancer even after neoadjuvant radiotherapy. Since LPLND is associated with postoperative morbidity, we should carefully select the candidate to maximize the effect of LPLND and minimize the morbidity caused by LPLND. Recent advancements in imaging study such as CT and MRI enable us to find the suitable candidates for LPLND. The morbidity caused by LPLND could be reduced by minimally invasive surgeries such as laparoscopic surgery and robotic surgery. We have to improve oncological outcomes and reduce morbidity by the multidisciplinary strategy for rectal cancer including total mesorectal excision, neoadjuvant chemoradiotherapy and LPLND together with laparoscopic surgery. PMID- 29795059 TI - Prevention of recurrent venous thrombosis and post-thrombotic syndrome. AB - BACKGROUND: This retrospective registry study evaluated different managements on the development of post-thrombotic syndrome (PTS) and recurrent deep venous thrombosis (R-DVT). The effects of aspirin (100 mg/day), added to the "standard management" (SM) (IUA consensus), were observed in patients after a proximal DVT. METHODS: The study started after the anticoagulant period. Comparable groups used the mild-antithrombotic agent Pycnogenol(r) (200 mg/day), ticlopidine (250 mg/day) or sulodexide (500 ULS/day). RESULTS: The groups were comparable for sex and age distribution and clinical pictures. In the SM group, 222 patients completed the follow-up (72 months). With SM, the percentage of patients with R DVT (requiring anticoagulants) was 17.2%; 19.8% of SM patients had a PTS. In the aspirin group (202 subjects), R-DVT was observed in 14.8% of patients; 17.32% had a PTS. The reduction in R-DVT and PTS with aspirin was significant (P<0.05) vs. the SM. There was no tolerability problem in subjects using Pycnogenol(r) (137 patients); they had a much lower incidence of R-DVT (5.8%) and PTS (6.5%) vs. SM and aspirin (P<0.05). Ticlopidine (121 patients) reduced the incidence of R-DVT (12.4%) and PTS (19.8% of patients) (P<0.05 vs. SM). With sulodexide the incidence of R-DVT was 6.7% (P<0.05 vs. SM); the incidence of PTS was 16.6% (P<0.05 vs. SM). The combined R-DVT+PT syndrome was observed in 14.9% of subjects using SM and in 12.9% of subjects using aspirin (P<0.05 vs. SM), in 3.6% of subjects managed with Pycnogenol(r) (<0.05% vs. aspirin and all other managements). The incidence was 10.74% with ticlopidine and 6.7% with sulodexide (both significantly lower than SM). CONCLUSIONS: Interaction between PTS and R DVT are complex; recurrences cause more PTSs, and a post-thrombotic limb is prone to R-DVT. Aspirin, for patients that can tolerate it, reduces the occurrence of PTS and R-DVT. In addition, ticlopidine and sulodexide are effective. Pycnogenol(r) is the most effective and safe for R-DVT and particularly PTS. Its full range of anti-thrombotic activity is now under evaluation. PMID- 29795063 TI - Modified Paul-Mikulicz jejunostomy in frail geriatric patients undergoing emergency small bowel resection. AB - BACKGROUND: Proximal or extended bowel resections are sometimes necessary during emergency surgery of the small bowel and call for creating a high small bowel stomy as a part of damage control surgery. Secondary restoration of intestinal continuity in the frail geriatric patient, further weakened by subsequent severe malabsorption may be prohibitive. METHODS: Six patients underwent emergency small bowel resection for proximal jejunal disease (83.3% highgrade adhesive SBO and 16.7% jejunal diverticulitis complicated with perforation (16.7%). With the intention to avoid end jejunostomy and the need for repeat laparotomy for bowel continuity restoration we modified the classic PaulMikulicz jejunostomy. RESULTS: The postoperative course was uneventful in four patients whose general condition improved considerably. At sixmonth followup, neither patients required parenteral nutrition. CONCLUSIONS: This modified stoma can be having the advantage of allowing a partial passage of the enteric contents, reducing the degree of malabsorption, and rendering jejunostomy reversal easy to perform later. PMID- 29795064 TI - Gallstone ileus in elderly patients. PMID- 29795065 TI - Early surgical management of acute cholecystitis in ultra octogenarian patients: our 5 years experience. AB - BACKGROUND: Acute calculous cholecystitis is a leading cause for hospital admission especially in developed countries. As older age population increases, medical research should consider the efficacy of all therapeutic options, including early surgical procedure in an emergency context, for the treatment of acute cholecystitis in elderly high risk patients. METHODS: From 01/01/2012 to 31/12/2016, 245 patients were admitted to our Institution with diagnosis of acute cholecystitis and managed with cholecistectomy within the same hospitalization. The study population was divided into 2 subgroups: group A (patients aged more than 80 years) and group B (patients within the limit of 80 years of age); the objective of the study was to evaluate and compare the surgical outcomes of the 2 groups in terms of conversion rate, mortality rate, overall morbidity and procedure - related complication rates. RESULTS: Statistical analysis did not show significant differences between ultra octogenarian and younger patients in terms of conversion to open procedure, iatrogenic bile duct lesions, postoperative peritoneal bleeding, bile leakage and peritoneal collection; no differences in terms of hospital stay have been demonstrated. Mortality and overall morbidity rates, even if similar to what observed in Literature and within acceptable values, were significantly higher in elderly patients, due to the presence of severe comorbidities leading to potentially fatal postoperative events. CONCLUSIONS: Minimally invasive approach in an emergency setting for acute cholecystitis seems to be a feasible and adequate therapeutic approach for extremely aged high risk patients. PMID- 29795067 TI - Not all diverticulitis are colonic: small bowel diverticulitis, a systematic review. AB - INTRODUCTION: Small bowel non Meckelian diverticulitis (SBNMD) is not so uncommon cause of admission in departments of emergency surgery. Our aim is to highlight signs and symptoms for early diagnosis and report proper surgical treatments. EVIDENCE ACQUISITION: The systematic review protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocol (PRISMA-P). EVIDENCE SYNTHESIS: Twelve studies met our inclusion criteria. Five hundred twenty seven patients diagnosed with SBNMD were analyzed: there were 159 (30%) cases of diverticular bleeding, 125(23%) cases of perforated SBNMD , 91 (17.26%) cases of intestinal obstruction, 79(14.9%) cases of non complicated diverticulitis, and 36(6.8%) cases of ileal diverticulosis. Among bleeding patients, endoscopy procedures were performed in 51(32%) cases. Surgery was necessary in 77/159 (48.4%) cases. Medical treatment was sufficient in 15/159 (9.4%) cases. In case of perforation, 93/125 (74.4%) patients were submitted to surgery, with open technique in 78/93 (83.8%) patients, by laparoscopy in 2/93 (2.1%) with conversion rate of 1.07%. Eight/125 (6.4%) cases received medical treatment.In case of obstruction, non operative management was effective in 3/91 (3.2%) cases. Surgery was performed in 74/91 (78%) cases, with open technique in 64/91 (86.4%) cases, by laparoscopy in 3/74 (4%), with one patient converted in laparotomy. CONCLUSIONS: Diagnosis of SBNMD is often made at emergency surgical exploration with high morbidity and mortality rate. SBNMD must be considered in elderly patients presenting with abdominal pain. Multidisciplinary approach to patient (radiologist, surgeon, gastroenterologist) is necessary to make early diagnosis. In case of complicated SBNMD, emergency surgeon has to choose the right surgical treatment, if necessary. PMID- 29795068 TI - Prevention of esophageal strictures after circumferential endoscopic submucosal dissection. AB - Endoscopic submucosal dissection or widespread endoscopic resection allow the radical removal of circumferential or near-circumferential neoplastic esophageal lesions. The advantage of these endoscopic methods is mini-invasivity and low risk of major adverse events compared to traditional esophagectomy. The major drawback of these extensive resections is the development of stricture - the risk is 70-80% if more than 75% of the circumference is removed and almost 100% if the whole circumference is removed. Thus, an effective method to prevent post-ER/ESD esophageal stricture would be of major benefit, because treatment of strictures requires multiple sessions of endoscopic dilatation and may carry a risk of perforation. Moreover, not all strictures are easy to treat and some patients may develop refractory strictures. There are several techniques and methods, which have been tested in both experimental and/or clinical studies but no one has received general acceptance based on results of high-quality evidence. The studies are usually small with a limited number of patients, there is a lack of randomized controlled trials and some techniques have been described only in experimental studies. Thus, prevention of post-ESD strictures remains an unresolved issue. On the other hand, because of the high risk of stricture and partially proven effectiveness of some preventive techniques, a preventive strategy should be considered in patients undergoing extensive ER/ESD in the esophagus. There is, however, no evidence about the superiority or inferiority of a particular preventive strategy compared to other techniques, moreover, there is paucity of data assessing the effectiveness of the combination of different preventive methods. The best preventive strategies known so far include 1) oral or local administration of corticosteroids; and 2) preventive stenting. Other strategies (preventive sessions of endoscopic dilatation or tissue engineering methods) have unproven efficacy or are too demanding for practical use. Nevertheless, the use of (any) preventive strategy after extensive ER/ESD of the esophagus probably reduces the risk of stricture and the number of endoscopic dilatations, therefore, it should be considered in these patients. However, there is a need for high quality evidence as well as for new ideas and approaches to resolve this important clinical problem. PMID- 29795069 TI - Can the depth of invasion of early esophageal cancer be predicted based on endoscopic evidence? AB - INTRODUCTION: Esophageal cancer is one of the leading causes of cancer-related death worldwide. Its poor prognosis is related to an often late diagnosis. An earlier diagnosis and treatment however, is related to a better outcome. Early stage esophageal cancer can be diagnosed and treated endoscopically with minimally invasive techniques, which is associated with lower mortality and morbidity than surgery. Whether esophageal carcinoma can be treated endoscopically depends mainly on the risk of lymph node metastasis, which itself correlates to the invasion depth of the tumor. The question is whether endoscopy can accurately determine the invasion depth and thus the treatment modality. EVIDENCE ACQUISITION: Articles used for this review were identified by searches of PubMed and references of relevant articles. EVIDENCE SYNTHESIS: Lesion morphology has some predictive value for the depth of invasion for squamous cell carcinoma (SCC) and esophageal adenocarcinoma (EAC). An intramucosal cancer generally has a flat appearance (Paris 0-IIa, 0-IIb,). By contrast, a submucosally invasive cancer often has an excavated (0-IIc, 0-III) and sometimes a polypoid morphology (0-I). In SCC, classification of surface vessels and intrapapillary capillary loops (IPCLs) allows accurate assessment of invasion depth. Generally, mucosal lesions are an indication for endoscopic treatment. However recent studies have shown that tumors with submucosal infiltration and low risk profile for metastasis can also be treated safely by endoscopic resection. CONCLUSIONS: Endoscopic assessment allows a rather accurate estimation of invasion depth of early esophageal cancer. To determine the final treatment modality however the final histological staging obtained by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is crucial. PMID- 29795070 TI - Endoscopic treatment of early esophageal adenocarcinoma. AB - The incidence of esophageal adenocarcinoma is on the rise. With advances in endoscopic techniques and imaging technology, early neoplastic lesions are being increasingly detected and treated. Managing early esophageal adenocarcinoma with endoscopic techniques is now considered the cornerstone of therapy, offering an alternative to surgery. The available endoscopic techniques can be broadly categorized into resection and ablation techniques that may be combined to increase the effectiveness of therapy. However, endoscopic treatments are highly specialized and patients with early adenocarcinoma should be referred to centers with expertise in advanced endoscopy of the esophagus. We review the proper method for conducting a thorough evaluation of early neoplastic lesions, staging details, the available endoscopic resection and ablation techniques, and the efficacy and safety of different endoscopic treatments. PMID- 29795071 TI - Autism spectrum disorders in children affected by Duchenne muscular dystrophy. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most frequent and severe form of the dystrophinopathies. The literature shows that about 30-40% of DMD subjects have intellectual disability. In males with Duchenne muscular dystrophy, neuropsychiatric disorders have also been observed: attention deficit disorder and hyperactivity, autism spectrum disorders, and obsessive-compulsive disorder. Duchenne muscular dystrophy is not just a muscle disorder, but also a disease that affects the brain. The aim of the present study was to describe a case series of children with Duchenne muscular dystrophy that have also the presence of autism spectrum disorders (ASDs). They have been assessed by means of standardized autism scales and the most appropriate psycho-educational treatment is herein discussed. METHODS: In order to evaluate and identify the presence and intensity of autistic symptoms have been used the Childhood Autism Rating Scale and Autism Diagnostic Observation Schedule tools. Moreover, in order to assess the intelligence of subjects and their lower limb function, Wisch-R intelligence scale and Vignos function scale were used, respectively. RESULTS: Atypical behaviors included a preference for being alone, and selective interest in privileged objects used in a stereotyped manner, motor fretting, and attention instability were present in all children. By the administration of these scales was confirmed the presence of an autism spectrum disorders in all subjects. CONCLUSIONS: It is important for clinical practice to consider this association increased. PMID- 29795073 TI - New trends in pediatric surgery: future perspectives. PMID- 29795066 TI - Non-operative management of rectal cancer: understanding tumor biology. AB - The management of locally-advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and long-term sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize non-operative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease. PMID- 29795074 TI - Management of posterior urethral valves in fetuses and neonates: a critical point of view. PMID- 29795072 TI - Palivizumab prophylaxis, respiratory syncytial virus and subsequent development of asthma. AB - BACKGROUND: Respiratory syncytial virus (RSV) infection is a disease commonly encountered during childhood and it may relapse. An experience in the early childhood would induce asthma development in the future. Palivizumab has a proven efficacy for the RSV prophylaxis so it may prevent asthma. Our aim was to evaluate the possible protective effect of palivizumab on the development of asthma by using the modified Asthma Predictive Index (mAPI). METHODS: This study's data consist of 339 children between 2 to 5 years of age followed up in healthy children unit from 2008 to 2011. Cases were evaluated in terms of wheezing frequency and characteristic features. Evaluations were performed among three groups; palivizumab-treated children born preterm (group 1), palivizumab untreated children born preterm (group 2) and term newborn children (group 3) with equal number of patients in each group (N.=113). RESULTS: Frequency of the answers about children's experienced wheezing times was significant between groups (P=0.003). A significant difference was found between the groups in terms of the clinician who diagnosed asthma (P=0.045). The groups were compared in terms of the mAPI positivity and a significant difference was found among the groups (P=0.001). Group 1 had lowest and group 3 had highest positivity. Group 1 and group 3 were different (P=0.000), group 2 was found higher than group 1, but was similar to group 3 (P=0.628). CONCLUSIONS: This study supports the benefit of administration of palivizumab to premature children to reduce the risk of asthma development. PMID- 29795075 TI - Notes from the Field: Vaccine Administration Errors Involving Recombinant Zoster Vaccine - United States, 2017-2018. PMID- 29795076 TI - Use of Outpatient Rehabilitation Among Adult Stroke Survivors - 20 States and the District of Columbia, 2013, and Four States, 2015. AB - Stroke is a leading cause of mortality and disability in the United States (1,2). Approximately 800,000 American adults experience a stroke each year (2,3). Currently, approximately 6 million stroke survivors live in the United States (2). Participation in stroke rehabilitation (rehab), which occurs in diverse settings (i.e., in-hospital, postacute care, and outpatient settings), has been determined to reduce stroke recurrence and improve functional outcomes and quality of life (3,4). Despite longstanding national guidelines recommending stroke rehab, it remains underutilized, especially in the outpatient setting. Professional associations and evidence-based guidelines support the increasing stroke rehab use in health systems and are promoted by the public health community (3-6). An analysis of 2005 Behavioral Risk Factor Surveillance System (BRFSS) data revealed that 30.7% of stroke survivors reported participation in outpatient rehab for stroke after hospital discharge in 21 states and the District of Columbia (DC) (7). To update these estimates, 2013 and 2015 BRFSS data were analyzed to assess outpatient rehab use among adult stroke survivors. Overall, outpatient rehab use was 31.2% (20 states and DC) in 2013 and 35.5% (four states) in 2015. Disparities were evident by sex, race, Hispanic origin, and level of education. Focused attention on system-level interventions that ensure participation is needed, especially among disparate populations with lower levels of participation. PMID- 29795078 TI - QuickStats: Percentage of Adults Aged 18-64 Years with Current Asthma,* by State National Health Interview Survey,? 2014-2016. PMID- 29795079 TI - Erratum: Vol. 67, No. 16. PMID- 29795077 TI - Vaccination Coverage Among Children Aged 2 Years - U.S. Affiliated Pacific Islands, April-October, 2016. AB - Vaccine-preventable diseases (VPDs) cause substantial morbidity and mortality in the United States Affiliated Pacific Islands (USAPI).* CDC collaborates with USAPI immunization programs to monitor vaccination coverage. In 2016, ? USAPI immunization programs and CDC piloted a method for estimating up-to-date status among children aged 2 years using medical record abstraction to ascertain regional vaccination coverage. This was the first concurrent assessment of childhood vaccination coverage across five USAPI jurisdictions (American Samoa; Chuuk State, Federated States of Micronesia [FSM]; Commonwealth of the Northern Mariana Islands [CNMI]; Republic of the Marshall Islands [RMI]; and Republic of Palau).S Differences in vaccination coverage between main and outer islands were assessed for two jurisdictions where data were adequate.** Series coverage in this report includes the following doses of vaccines: >=4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP); >=3 doses of inactivated poliovirus vaccine (IPV); >=1 dose of measles, mumps, and rubella vaccine (MMR); >=3 doses of Haemophilus influenzae type B (Hib) vaccine; >=3 doses of hepatitis B (HepB) vaccine; and >=4 doses of pneumococcal conjugate vaccine (PCV); i.e., 4:3:1:3:3:4. Coverage with >=3 doses of rotavirus vaccine was also assessed. Completion of the recommended series of each of these vaccines?? was <90% in all jurisdictions except Palau. Coverage with the full recommended six-vaccine series (4:3:1:3:3:4) ranged from 19.5% (Chuuk) to 69.1% (Palau). In RMI and Chuuk, coverage was lower in the outer islands than in the main islands for most vaccines, with differences ranging from 0.9 to 66.8 percentage points. Medical record abstraction enabled rapid vaccination coverage assessment and timely dissemination of results to guide programmatic decision-making. Effectively monitoring vaccination coverage, coupled with implementation of data-driven interventions, is essential to maintain protection from VPD outbreaks in the region and the mainland United States. PMID- 29795080 TI - HIV Preexposure Prophylaxis in the U.S. Military Services - 2014-2016. AB - Human immunodeficiency virus (HIV) infection is a substantial health concern for the U.S. Department of Defense (DoD) and for service members stationed throughout the world. Each year, approximately 350 new HIV infections are diagnosed in members of the U.S. military services, with most infections acquired within the United States (1). The DoD populations most affected by HIV mirror those in the U.S. civilian population; the highest rates of new military diagnoses are in men and blacks or African Americans (blacks) (1). Blacks are disproportionally affected, and most new diagnoses occur among men who have sex with men (MSM). HIV preexposure prophylaxis (PrEP) is approximately 90% effective in preventing HIV infection when used properly (2), and an increasing number of active duty personnel have used HIV prevention services and PrEP in the military health system since the repeal of "Don't Ask, Don't Tell"* in 2011 (3). Military health system and service records were reviewed to describe HIV PrEP use among military personnel, and military health care providers were surveyed to assess HIV PrEP knowledge and attitudes. Among 769 service members prescribed PrEP during February 1, 2014-June 10, 2016, 60% received prescriptions from an infectious disease provider, 19% were black men, and 42% were aged >28 years. Half of surveyed military health care providers self-rated their PrEP knowledge as poor. DoD is developing new policy to address access to care challenges by defining requirements and establishing pathways for universal patient access to PrEP. PMID- 29795081 TI - Notes from the Field: Acute Poisonings from a Synthetic Cannabinoid Sold as Cannabidiol - Utah, 2017-2018. PMID- 29795082 TI - [Assessment of life quality and job satisfaction of neurosurgeons in the Russian Federation (a sociological study)]. AB - PURPOSE: The study purpose was to investigate and evaluate factors of career satisfaction among neurosurgeons in the Russian Federation. MATERIAL AND METHODS: During the pilot study, 217 neurosurgeons in the Russian Federation were surveyed in 2016. The survey was conducted through an anonymous voluntary questionnaire. The questionnaire consisted of four sections: 1) demographic data; 2) evaluation of professional stress factors; 3) characteristics of job satisfaction; 4) quality of life indicators. Responses in ordinal scales were evaluated using one dimensional frequency analysis; factors related to career satisfaction were assessed using correlation and regression analyses. RESULTS: More than 80% of the respondents were males under the age of 40, ordinary doctors, without a scientific degree, with less than 15 years of work experience, performing less than 150 operations a year, and receiving wages less than 60 thousand rubles per month. The most common negative job-related factors of occupational stress included a large amount of work with medical records and insufficient wages. Only 51% of neurosurgeons were in general satisfied with their career. The greatest dissatisfaction in more than 55% of respondents was associated with the lack of time for personal development. More than 83% of respondents considered their legal protection insufficient. A correlation analysis revealed the greatest correlation (about 0.4) between career satisfaction and opportunities for professional growth as well as between mutual understanding with colleagues and confidence in the future. In addition, a regression analysis revealed the following factors: time for doing science, confidence in a stable salary, work on weekends, knowledge of English, and insufficient supply of consumables. CONCLUSION: Career satisfaction of the neurosurgeon depends mainly on working conditions and confidence in career prospects. PMID- 29795083 TI - [Intraoperative fluorescence diagnostics in surgery of intracranial meningiomas: analysis of 101 cases]. AB - : Fluorescence diagnostics has been extensively applied in surgery of malignant brain gliomas. However, the use of this technique in surgery of intracranial meningiomas has remained controversial. OBJECTIVE: The study objective was to assess the sensitivity of 5-aminolevulinic acid-based (5-ALA) fluorescence diagnostics in surgery of brain meningiomas and to clarify the clinical and biological factors that may influence the fluorescent effect. MATERIAL AND METHODS: The study consistently included 101 patients with intracranial meningiomas of various locations who were operated on using 5-ALA. There were 28 (27.72%) males and 73 (72.27%) females (median age, 54 years). In all patients, surgery was performed using an operating microscope equipped with a fluorescent module; in 24 of these, laser spectroscopy was used. For comparison of chances to observe the fluorescent effect of 5-ALA in patients having meningiomas with different WHO histological grades (Grade I vs Grade II-III), we performed a meta analysis that included 10 studies (the largest series) on outcomes of surgical treatment of meningiomas using intraoperative fluorescence diagnostics. RESULTS: Of 101 patients included in this series, observable fluorescence was detected in 95 (94.1%) patients: weak fluorescence in 12 (11.9%), moderate fluorescence in 23 (22.8%) cases, and strong fluorescence in 60 (59.4%) patients. There was no statistically significant relationship (p>0.05) between the rate and intensity of observable fluorescence and the tumor growth pattern (primary/continued), location, WHO grade of malignancy, and histological subtype. In the absence of intraoperative bleeding, tumor fluorescence was statistically significantly brighter (p=0.02). Of 26 patients with hyperostosis, bone fluorescence was observed in 11 (42.3%) cases. There was no statistically significant relationship between administration of dexamethasone, its dose, administration of anticonvulsants, gastrointestinal tract diseases, as well as diabetes mellitus and the fluorescence intensity. There was also no significant relationship between the extent of tumor resection (Simpson scale) and the presence of fluorescence as well as its intensity. Comparison of the observable fluorescence intensity and the laser spectroscopy indicators revealed a significant correlation (r=0.75; p=0.005). CONCLUSION: Meningioma is a well fluorescent tumor, with the technique sensitivity being 94.1%. In some cases, the use of fluorescence diagnostics in surgery of meningiomas improves identification of residual tumor fragments and enables correction of a surgical approach. To assess the effect of fluorescence diagnostics on the recurrence rate and disease-free duration, further research is required. PMID- 29795084 TI - [Methods to assess competence of indirect cerebral revascularization in children]. AB - : The use of catheterization cerebral angiography (CCA) to assess collateral blood flow through an indirect anastomosis is traumatic for children, uses a high radiation dose, and requires anesthetic care in most cases. AIM: we aimed to compare the capabilities of triplex ultrasound (TU) of vessels, magnetic resonance angiography (MRA), computed tomography angiography (CTA), and CCA in assessing the competence of indirect cerebral revascularization (ICR) in children. MATERIAL AND METHODS: ICR was performed in 18 children in 24 hemispheres (24 operations). The results were evaluated by Matsushima classification-based comparison of the data of preoperative and postoperative clinical examinations, TU of the superficial temporal artery, magnetic resonance imaging (MRI) and computed tomography (CT) of vessels, and selective cerebral angiography. RESULTS: After surgery, improvements in the neurological and neuropsychological status were assessed. Matsushima grade A collaterals were found in 12 (50%) cases, grade B collaterals were present in 3 (13%) cases, grade C collaterals were present in 7 (29%) cases, and grade D collaterals were detected in 1 (4%) case; in 1 (4%) case, the superficial temporal artery was not enhanced. MR angiography visualized 18 (75%) indirect anastomoses, CT angiography revealed 4 indirect anastomoses, and TU visualized 4 indirect anastomoses. Comparison of preoperative and postoperative TU data for the superficial temporal artery revealed significant changes in blood flow in the form of increased rate indices and a decreased resistance index; mean values of indices for each angiographic class of revascularization and significant differences in pre- and postoperative observations were calculated. CONCLUSION: Examination of ICR competence using CCA is necessary in the presence of persistent clinical signs of chronic cerebral circulatory insufficiency, absence of increased blood flow and decreased peripheral resistance in the superficial temporal artery, and lack of anastomosis according to MRA. The most optimal techniques for postoperative examination are MRA with perfusion and diffusion maps and TU. PMID- 29795085 TI - [Spinal cord epidermoid cysts]. AB - : The article describes in detail a large modern clinical series of patients operated on for spinal cord epidermoid cysts. AIM: the study aim was to comprehensively investigate the epidemiological and clinical peculiarities of spinal cord epidermoid cysts and evaluate immediate and long-term results of their surgical treatment. MATERIAL AND METHODS: We describe and analyze surgical outcomes of 20 patients with spinal cord epidermoid cysts. This sample was selected from 554 patients with intramedullary tumors and 365 patients with spinal dysraphism (aged from 2 months to 72 years) who were operated on by the first author in 2002-2017. RESULTS: Our findings confirm a high efficacy and low risk of surgical treatment of patients diagnosed with spinal epidermoid cysts. Severe complications of disease progression serve as indications for 'preventive' surgery even in asymptomatic cases. Complete resection of the tumor capsule without deterioration of the functional surgical result is the main goal of surgical treatment. Incomplete resection is associated with a high risk of recurrence. The most thorough follow-up with annual MRI examination is necessary for the first 6 years after surgery. PMID- 29795086 TI - [Transpalpebral craniotomy in skull base surgery]. AB - : The concept of minimally invasive neurosurgery has significantly evolved in recent years, which is associated with improvements in diagnostics, microneurosurgical techniques, anesthesiology, and intraoperative imaging. MATERIAL AND METHODS: We present the preliminary results of using transpalpebral craniotomy in surgery of supratentorial aneurysms and anterior cranial fossa tumors. In the period between 2015 and 2107, we used this approach in surgical treatment of 30 aneurysms (10 aneurysms in the 'cold' period of hemorrhage and 20 unruptured aneurysms) and 10 anterior cranial fossa base tumors. The approach included a superior eyelid incision and a fronto-orbital craniotomy. We retrospectively evaluated outcomes, postoperative complications, and cosmetic results after these operations. The mean follow-up period was 6 months. RESULTS: There were no deaths, disabilities, or serious permanent approach-associated complications. All patients had expected periorbital edema that was not considered as a complication. CONCLUSION: Transpalpebral craniotomy is a safe and effective approach to anterior cranial fossa neoplasms and anterior circle of Willis aneurysms. This approach avoids injury to the frontal and temporal muscles as well as to the facial and trigeminal nerve branches. Patients assessed the postoperative cosmetic result as excellent. PMID- 29795087 TI - [A technique of manufacturing anatomical preparations of the human brain based on injecting vessels with colored silicone (a technical note)]. AB - OBJECTIVE: The objective was to produce anatomical preparations by injecting vessels with colored silicone to study the brain and skull base anatomy. MATERIAL AND METHODS: Fresh, undissected, and unfixed cadavers were used. The internal carotid arteries and internal jugular veins were identified on both sides of the neck. The vessels were washed with running water. Then, a complex solution consisting of white silicone rubber, silicone oil (solvent), and a coloring pigment (red and blue pigments) at a ratio of 1:(0.9-1.1):(0.04-0.06), respectively, was prepared. About 30-60 s before injecting the complex solution into the vessels, a catalyst-hardener was added to the solution at a ratio of 1:(0.05-0.07). The complex solution was first introduced into the internal carotid artery until the solution came out from the contralateral internal carotid artery; then, the solution was injected into the internal jugular vein until the solution emerged from the contralateral internal jugular vein. RESULTS: The technique enables quick and high-quality visualization of both large and very small vessels of the brain and skull base. CONCLUSION: The proposed simple and inexpensive technique of manufacturing anatomical preparations improves the quality of training and mastering of microsurgical skills in residents and practicing neurosurgeons. PMID- 29795088 TI - [Resection and correction of the common carotid artery to enable an endovascular approach for treatment of a giant ICA aneurysm (a case report and literature review)]. AB - The article reports a clinical case of endovascular treatment of a female patient with a giant aneurysm of the cavernous internal carotid artery complicated by gross ipsilateral bending of the proximal third of the common carotid artery. To ensure an adequate endovascular approach to the aneurysm, open repair of the common carotid artery and elimination of its bending were performed at the first stage. This enabled successful placement of a flow-diverting stent into the internal carotid artery at the aneurysm level at the second stage, resulting in good technical and clinical outcomes. We discuss the technical aspects of performed interventions and the opportunity of using this approach in patients who need endovascular interventions that are complicated by anatomical morphological changes in the brachiocephalic arteries. PMID- 29795089 TI - [Treatment of patients with ossifying arachnoiditis and progressive syringomyelia (analysis of three cases and a literature review)]. AB - : To date, only 12 cases of ossifying arachnoiditis with concomitant syringomyelia have been reported in the world literature. In this article, we presented our experience of treating three patients with syringomyelia associated with ossifying arachnoiditis. OBJECTIVE: based on the literature data and our own experience, we tried to define the most optimal treatment approach for this disease. MATERIAL AND METHODS: We analyzed the data of 15 patients (12 cases reported in the literature and 3 our own cases). The diagnosis was established on the basis of complaints, medical history, patient examination, MRI and CT of the spinal cord, and intraoperative data. Progression of syringomyelia was evaluated by comparison of the neurological status and calculation of the Vaquero index before and after surgery; the Domenicucci classification was used to evaluate the severity of ossifying arachnoiditis. Surgical treatment included several stages: decompressive laminectomy, elimination of spinal cord fixation, excision of ossifying arachnoiditis, shunting of the syrinx, and repair of the dura mater. RESULTS: An analysis of the patient data reported in the literature (12 cases) and those in our series (3) revealed that in the early postoperative period, 7 (46.7%) of these 15 patients had improvements, 5 (33.3%) patients had no changes, and 3 (20%) patients experienced a worsening. At present, there is no clear algorithm for diagnosing and treating this disease. CONCLUSION: Further investigation of the problem may facilitate an earlier diagnosis of the disease and provide more effective medical care. PMID- 29795090 TI - [Segmental agenesis of the cervical internal carotid artery with collateral blood supply from the ascending pharyngeal artery and intercavernous anastomosis: a clinical case and literature review]. AB - The article presents a clinical case of segmental agenesis of the cervical ICA with collateral blood supply to the ICA territory through the intercavernous anastomosis and ascending pharyngeal artery with the branching primitive stapedial artery - the aberrant ICA variant. A feature of the case is a unique combination of the intercavernous anastomosis and the aberrant ICA, which provide collateral blood flow in cervical ICA agenesis. In the world literature, there are no reports of similar combinations. The discussion provides information on the stages of circle of Willis formation and presents a literature review of cases of intercavernous anastomoses associated with ICA agenesis. PMID- 29795091 TI - [Treatment of postoperative vasospasm after insular tumor removal by intra arterial administration of verapamil (analysis of two clinical cases and a literature review)]. AB - PURPOSE: We describe our experience of using intra-arterial administration of Verapamil to resolve vasospasm in two patients who underwent surgery for insular glial tumors. MATERIAL AND METHODS: Severe vasospasm (an increased systolic LBFV in the M1 MCA, more than 250 cm/s, and a Lindegaard index of 4.1) was observed in 2 (3.2%) of 62 patients in the early postoperative period after removal of intracerebral insular tumors. In both cases, vasospasm was confirmed by angiography, was clinically significant, and manifested by the development of pyramidal hemisyndrome. RESULTS: Intra-arterial administration of Verapamil led to relief of angiospasm, which was confirmed by angiographic data, and complete regression of neurological symptoms. CONCLUSION: Vasospasm symptoms in patients after removal of insular tumors largely resemble those after aneurysm hemorrhage. An increase in the LBFV in the MCA and related neurological symptoms develop lately and persists for up to 2 weeks after surgery. LBFV values are similar to those in patients after SAH and reach 250-300 cm/s. Among the causes of focal symptoms developed after removal of insular tumors, injury to the inner capsule structures, injury to arteries of the MCA territory (especially perforators), and angiospasm should be differentiated. PMID- 29795092 TI - [Capabilities of 18F-FET PET/CT in a patient with brain glioma (a case report and literature review)]. AB - Positron emission tomography combined with computed tomography (PET/CT) enables assessment of not only anatomical and structural but also metabolic changes in tumor mass. 18F-fluoroethyl tyrosine (18F-FET) PET/CT is based on evaluation of transport of 18F-labeled tyrosine in tissues. We present a clinical case of a patient with a newly diagnosed brain tumor, demonstrating the capabilities of 18F FET PET/CT in assessing the reliable volume and degree of tumor anaplasia, which is important when choosing the treatment approach for a patient. PMID- 29795093 TI - [Nasal schwannoma with skull base destruction in a child (a case report and literature review)]. AB - Schwannomas (neurinomas) are benign, encapsulated, and slow-growing neoplasms developing from any peripheral, cranial, or vegetative nerve that has the Schwann sheath. Schwannomas of the nasal cavity and paranasal sinuses in adults occur rarely, less than 4% of cases. The world literature lacks similar data for the pediatric age group because these tumors in children are unique and extremely rare. The most common clinical symptoms of sinonasal schwannoma are nasal breathing disorders, hyposmia or anosmia, and snoring at night. Other symptoms are associated with intranasal schwannoma invasion of neighboring organs and tissues and include exophthalmos, epiphora (lacrimation), headaches, and anesthesia in the facial area. In this article, we describe a rare case of diagnosis and successful surgical treatment of a child with intranasal schwannoma destructing the skull base. PMID- 29795094 TI - [Chronic sacral nerve electrostimulation in treatment of neurogenic pelvic organ dysfunction in children]. AB - : Myelodysplasia is the most common cause of congenital pelvic abnormalities in children. The causes of acquired neurogenic pelvic dysfunctions in children include spinal cord injury, myelitis, and neurodegenerative diseases. Urination impairments in children with neurological disorders are a serious clinical problem. In most cases, the capabilities of conservative treatment of pelvic organ dysfunctions are limited. One of the most promising directions in treatment of neurogenic urination disorders is modeling of a lost urination mechanism using direct or mediated electrostimulation of the nerve fibers of the sacral plexus - neuromodulation. AIM: the review aim is to describe the technique and results of chronic sacral neurostimulation in treatment of pelvic organ disorders in children, which have been reported in the international literature. An obligatory condition for application of chronic sacral neurostimulation (CSNS) is a positive clinical response to test electrostimulation of the S3 nerve root. The test period duration is 1-3 weeks. In the case of a positive effect, a permanent system is implanted for neurostimulation of the S3 nerve root. On treatment with CSNS, children with severe urinary incontinence had a significant decrease in the rate of incontinence episodes, and patients with urinary retention had no or reduced need for periodic catheterization. Therefore, the accumulated experience of using CSNS in children with spinal cord diseases indicates the need in further study of the technique capabilities for correction of pelvic organ dysfunctions. PMID- 29795095 TI - [The use of activated recombinant factor VII in neurosurgery]. PMID- 29795096 TI - [Legislative regulatory framework for medical care quality and safety control]. AB - The paper presents the analysis of legislative and regulatory framework for the control of the quality and safety of medical activities. Legislative and regulatory framework requires mandatory internal control of the quality and safety of medical activities and dictates its structure. In the development of the internal control of the quality and safety of medical activities there is, however, a need to consider medical and social, legal, organizational, ethical and economic issues. PMID- 29795097 TI - [Criteria for quality assessment and labor payment for dental care professionals]. AB - Internal regulatory documents of the medical organization reflecting the calculation of incentive payments and a personalized assessment of the quality of dental care were analyzed. It is found that until now the new system of wage payment has not solved the problem of stimulating dental care professionals depending on the results of their work and needs to be changed. The applied criteria of quality assessment and the intensity of labor must have measurable parameters that exclude subjective appraisal; the integrative coefficient of labor quality must be created. A transparent mechanism of wage payment is also needed in order to motivate staff highly to achieve the qualitative and quantitative indicators of labor that are incorporated in it by the medical organization authority and are related with their work goals. Every criterion outlined in the 'Regulation on Inner Control of the Quality and Safety of Dental Care' should reflect the intensity and quality of dental services and correspond with the criteria of the incentive premiums calculation, that have been prescribed in the 'Wage payment regulations'. PMID- 29795098 TI - [Quality assessment and organization of dental care in the regions of Russian Federation]. AB - On the basis of a survey of 732 patients of dental clinics as one of the most informative methods of assessing the quality of medical care, it was concluded that the satisfaction of the population in the conditions and quality of dental care is at a high level. PMID- 29795099 TI - [The role of Wnt/beta-catenin signaling pathway in ameloblastoma formation]. AB - : The aim of the study was to assess the role of the canonical Wnt/beta-catenin signaling pathway in the formation and clinical course of various histological variants of ameloblastoma. MATERIAL AND METHODS: 76 cases of ameloblastoma were investigated, the average age of the patients was 46 years. There were 49 (64.5%) cases of recurrence of the disease. Tissue antigens were determined using monoclonal rabbit antibodies to Ki-67 and beta-catenin. RESULTS: it was found correlation between the proliferative activity of ameloblastoma cells and the intranuclear localization of beta-catenin, indicating the activation of the Wnt/beta-catenin-signaling pathway. It was shown that the nuclear localization of beta-catenin is positively correlated with the recurrence. CONCLUSION: The Wnt/beta-catenin signaling pathway is involved in a formation and progression of ameloblastoma. PMID- 29795100 TI - [In vitro evaluation of two methods for fractured screw retrieval from dental implants]. AB - The aim of the study was to compare estimated efficiency of fractured dental implant screw removal methods. Twenty screws in implant internal connections were fractured in animal model to test fragment retrieval comparing two methods: using ultrasonic tools (group 1, 10 implants) and special reverse force kit (group 2, 10 implants). Removing screws with ultra-sonic tools proved to be slightly more effective, than using specialized kit. Mean procedure time in group 1 was 4 min more than in group 2. The possibility of screw retrieval correlates with fracture level, as deeper fractured screws were the easiest ones to remove. PMID- 29795101 TI - [Age related molecular-genetic preconditions for dental caries in pregnant women]. AB - The aim of the study was to evaluate the allelic polymorphisms kallikrein-4 (KLK 4) gene at the mutant points: G2664153A and G2142A in pregnant women under and over 30 of age. In pregnant women with KLK-4 gene polymorphisms A/A and G/A genotypes the rate of tooth decay growth increases in spite of applying the ternary calcium-phosphate-fluoride-containing gel. This genotype is also associates with unfavorable alteration of such oral fluid indicators as pH, concentrations of inorganic phosphorus, the active concentrations of calcium and potassium, as well as the ratio of total calcium and phosphorus concentrations, the active concentrations of electrolytes, and demineralizing activity of oral fluid. PMID- 29795102 TI - [Differential diagnosis of dental enamel focal demineralization and fluorosis by means of spectrophotometry]. AB - The article presents the results of spectrophotometric tooth enamel scanning for differential diagnosis of focal enamel demineralization and fluorosis. Research was conducted in vivo on teeth affected by these diseases. VITA EasyShade spectrophotometer measurements were made on the affected area and on the visually healthy part of enamel. The lightness appeared as the only one differential significant optical characteristics of tooth enamel. Lightness metrics were higher in the case of initial caries than on the healthy part of enamel when these metrics were lower in the case of fluorosis than on the healthy part of enamel. PMID- 29795103 TI - [Rationale for caries prevention in young adults based on caries resistance rates]. AB - The aim of the study was to evaluate the effectiveness of caries prevention in young adults with different caries resistance rates. Sixty-seven patients aged 18 20 with low (n=32) and high (n=35) dmft were enrolled in the study. Caries prevention efficacy was assessed by laboratory tests: enamel resistance test (ERT), clinical enamel remineralization speed test (CERST), estimation of calcium and inorganic phosphorus in oral fluid. Patients with high caries activity in addition to conventional prevention program received prophylaxis procedure with Clinpro White Varnish (3M ESPE). ERT and CERST were significantly higher in high dmft (>13) subgroup. Statistically significant difference in ERT and CERST was observed between subgroups at 3 and 6 months evaluation after prevention program. PMID- 29795104 TI - [General anesthesia and intensive care for patients surgically treated for deep neck odontogenic infections]. AB - The study objectives were to determine the significance of deep neck odontogenic infections severity to predict the postoperative morbidity. Observational study was conducted in 2014-2015. A continuous sample of 38 patients who were urgently hospitalized in the Novosibirsk Regional Clinical Hospital with deep neck odontogenic infections and operated on the day of hospitalization was analyzed. SAPS scale rates correlated positively with the duration of the artificial lungs ventilation (ALV). The positive balance of the introduced and withdrawn liquid in the first day of the postoperative period is associated with the ALV duration, which requires accurate dosing of the infusion volumes. The described protocol of perioperative care significantly decreases morbidity in patients with deep neck odontogenic infections. PMID- 29795105 TI - [Anatomic rationale for clinical efficacy of intraosseous mental nerve anesthesia]. AB - The aim of the study was to prove the anatomical and clinical effectiveness of the modified anesthesia of mental nerve. The effectiveness of conductive anesthesia near the mental foramen was objectively evaluated using the electric pulp test (EPT) in 100 volunteers of both sexes, aged 35-43 years. Wet anterior mandible preparations obtained from 350 cadavers aged 18-74 years were also studied. EPT value after local mental anesthesia conducted according to Malamed C. using 4% articain solution of local anesthetic with vasoconstrictor concentration of 1:200.000 after 2 minutes was 93+/-0.82 mA, after 4 minutes - 188+/-1.26 mA. Yield variability indicators of intraosseous mental nerve anesthesia was slightly higher varying from 94.11 mA to 96.61 mA after 2 minutes and from 197.4 to 199.92 mA after 4 minutes survey. The study showed the efficiency and predictability of intraosseous anesthesia of the mental nerve. PMID- 29795106 TI - [Osteointegration of dental implants in augmented bone after bone flap rotation]. AB - The article presents clinical case of a patient with partial secondary absence of teeth and maxillary defect because of vertical alveolar bone atrophy. Vertical alveolar ridge augmentation by osseous flap rotation and xenogenous bone block with 10% collagen was performed. Eight months later 4 dental implants with modified surface were placed in the augmentation area. After 3 months 3 implants showed no signs of osteointegration and were removed. Three week later the patient was admitted to ENT department because of maxillary sinusitis symptoms. PMID- 29795107 TI - [Long-term clinical results of surgical treatment in patients with salivary stone disease and ducts deformation of the parotid gland]. AB - The authors with the goal of postoperative dynamic control over the results of surgical treatment of patients previously operated for salivary stone disease and various ducts deformations of the parotid salivary glands examined 16 patients with an observation period up to 8 years. It was found that recurrent acute parotitis or recurrence of stone formation was observed in 100% of cases. The authors developed methods of surgical treatment leads to long-term clinical success with no recurrence of the disease. PMID- 29795108 TI - [Correlation of TMJ structures and craniocervical area position in partial dental loss]. AB - The purpose of the study was to determine the correlation features in position of the TMJ and the atlantoaxial compound in presence of dentition defects. The study included 20 patients (10 males and 10 females) aged 37 to 59 years with mandible terminal dentition defects. The comparison group included 20 patients of men and women equally, aged from 18 to 29 years with intact dentition. All patients were diagnosed with CT scan of the maxillofacial area, including the craniovertebral zone. In the analysis of the TMJ, the ratio of bone structures were determined by studying the CT scan in sagittal plane. The position of the elements of the atlantoaxial compound were evaluated on CT scan in frontal and transversal plane along the distance from the lateral masses of the CI vertebrae to the dens CII process. In persons with one-sided terminal dentition defect any changes of the position of the TMJ elements were not determined except for the right L1 parameter (8.91+/-0.45 mm and 6.8+/-0.77 mm, respectively, p=0.020). At the same time, the L1 distance on the left significantly changed to 6.86+/-0.40 mm relative to the comparison group (8.21+/-0.77 mm, p=0.030). In contrast to the ratio of the bony structures of the TMJ on the analysis of the craniocervical zone we determined the differences in the relationships of all elements of the atlantoaxial compound. The asymmetry index of CI-CII in the study group was 1.12+/-0.15 mm, in the comparison group 0.1+/-0.02 mm, p=0.001. The correlation analysis of the investigated structures showed different variants of the relation (direct and inverse) between the L1, L5 parameters of the TMJ and the distance from the lateral masses CI to dens CII. The structures of the TMJ in the presence of dentition defects remain practically unchanged and are more stable, it can be assumed that the primary link which undergo the changes considering the relationship between bone structures is the atlantoaxial junction. PMID- 29795109 TI - [Natural amelogenesis and rationale for enamel regeneration by means of robotic bioprinting of tissues in situ]. PMID- 29795110 TI - [Clinical manifestations of syphilis in maxillofacial area. Part I]. PMID- 29795111 TI - Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development. AB - Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide. As obesity and diabetes become more prevalent, the contribution of non alcoholic fatty liver disease (NAFLD) to HCC is rising. Recently, we reported intrahepatic CD4+ T cells are critical for anti-tumor surveillance in NAFLD. Lipid accumulation in the liver is the hallmark of NAFLD, which may perturb T cell function. We sought to investigate how the lipid-rich liver environment influences CD4+ T cells by focusing on carnitine palmitoyltransferase (CPT) family members, which control the mitochondrial beta-oxidation of fatty acids and act as key molecules in lipid catabolism. Linoleic acid (C18:2) co-localized within the mitochondria along with a corresponding increase in CPT gene upregulation. This CPT upregulation can be recapitulated by feeding mice with a high-C18:2 diet or the NAFLD promoting methionine-choline-deficient (MCD) diet. Using an agonist and antagonist, the induction of CPT genes was found to be mediated by peroxisome proliferator-activated receptor alpha (PPAR-alpha). CPT gene upregulation increased mitochondrial reactive oxygen species (ROS) and led to cell apoptosis. In vivo, using liver-specific inducible MYC transgenic mice fed MCD diet, blocking CPT with the pharmacological inhibitor perhexiline decreased apoptosis of intrahepatic CD4+ T cells and inhibited HCC tumor formation. These results provide useful information for potentially targeting the CPT family to rescue intrahepatic CD4+ T cells and to aid immunotherapy for NAFLD promoted HCC. PMID- 29795112 TI - Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress. AB - Exposure of male mice to early life stress alters the levels of specific sperm miRNAs that promote stress-associated behaviors in their offspring. To begin to evaluate whether similar phenomena occur in men, we searched for sperm miRNA changes that occur in both mice and men exposed to early life stressors that have long-lasting effects. For men, we used the Adverse Childhood Experience (ACE) questionnaire. It reveals the degree of abusive and/or dysfunctional family experiences when young, which increases risks of developing future psychological and physical disorders. For male mice, we used adolescent chronic social instability (CSI) stress, which not only enhances sociability defects for >1 year, but also anxiety and defective sociability in female offspring for multiple generations through the male lineage. Here we found a statistically significant inverse correlation between levels of multiple miRNAs of the miR-449/34 family and ACE scores of Caucasian males. Remarkably, we found members of the same sperm miRNA family are also reduced in mice exposed to CSI stress. Thus, future studies should be designed to directly test whether reduced levels of these miRNAs could be used as unbiased indicators of current and/or early life exposure to severe stress. Moreover, after mating stressed male mice, these sperm miRNA reductions persist in both early embryos through at least the morula stage and in sperm of males derived from them, suggesting these miRNA changes contribute to transmission of stress phenotypes across generations. Since offspring of men exposed to early life trauma have elevated risks for psychological disorders, these findings raise the possibility that a portion of this risk may be derived from epigenetic regulation of these sperm miRNAs. PMID- 29795113 TI - Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma. AB - Epidemiological studies have demonstrated that metformin could mitigate the progression of several tumors. Although it has been proved that metformin could cause demethylation of DNA and lead to up-regulation of some encoding genes and non-coding RNAs, there is little data about the effects of metformin on metastasis, and the interaction between metastasis and autophagy in human osteosarcoma cells. Here, we found miR-570-3p was significantly down-regulated in human metastatic osteosarcoma tissues but not in non-metastatic osteosarcoma tissues. Metformin attenuates the metastasis and autophagy in osteosarcoma. Interestingly, this autophagy favors osteosarcoma cells invasion. Moreover, reduction of metformin-induced inhibition of autophagy could reverse the invasion suppression in osteosarcoma. Mechanistically, metformin increases miR-570-3p by the demethylation of DNA, and the upregulation of miR-570-3p repressed the translation of its target, LCMR1 and ATG12. Our results, for the first time, presents evidence that the miR-570-3p-mediated suppression of LCMR1 and ATG12 is involved in the metformin-induced inhibition of metastasis in osteosarcoma cells. PMID- 29795115 TI - Separation of current density and electric field domains caused by nonlinear electronic instabilities. AB - In 1963 Ridley postulated that under certain bias conditions circuit elements exhibiting a current- or voltage-controlled negative differential resistance will separate into coexisting domains with different current densities or electric fields, respectively, in a process similar to spinodal decomposition of a homogeneous liquid or disproportionation of a metastable chemical compound. The ensuing debate, however, failed to agree on the existence or causes of such electronic decomposition. Using thermal and chemical spectro-microscopy, we directly imaged signatures of current-density and electric-field domains in several metal oxides. The concept of local activity successfully predicts initiation and occurrence of spontaneous electronic decomposition, accompanied by a reduction in internal energy, despite unchanged power input and heat output. This reveals a thermodynamic constraint required to properly model nonlinear circuit elements. Our results explain the electroforming process that initiates information storage via resistance switching in metal oxides and has significant implications for improving neuromorphic computing based on nonlinear dynamical devices. PMID- 29795114 TI - Probing the pathways of free charge generation in organic bulk heterojunction solar cells. AB - The fact that organic solar cells perform efficiently despite the low dielectric constant of most photoactive blends initiated a long-standing debate regarding the dominant pathways of free charge formation. Here, we address this issue through the accurate measurement of the activation energy for free charge photogeneration over a wide range of photon energy, using the method of time delayed collection field. For our prototypical low bandgap polymer:fullerene blends, we find that neither the temperature nor the field dependence of free charge generation depend on the excitation energy, ruling out an appreciable contribution to free charge generation though hot carrier pathways. On the other hand, activation energies are on the order of the room temperature thermal energy for all studied blends. We conclude that charge generation in such devices proceeds through thermalized charge transfer states, and that thermal energy is sufficient to separate most of these states into free charges. PMID- 29795116 TI - Trait paranoia shapes inter-subject synchrony in brain activity during an ambiguous social narrative. AB - Individuals often interpret the same event in different ways. How do personality traits modulate brain activity evoked by a complex stimulus? Here we report results from a naturalistic paradigm designed to draw out both neural and behavioral variation along a specific dimension of interest, namely paranoia. Participants listen to a narrative during functional MRI describing an ambiguous social scenario, written such that some individuals would find it highly suspicious, while others less so. Using inter-subject correlation analysis, we identify several brain areas that are differentially synchronized during listening between participants with high and low trait-level paranoia, including theory-of-mind regions. Follow-up analyses indicate that these regions are more active to mentalizing events in high-paranoia individuals. Analyzing participants' speech as they freely recall the narrative reveals semantic and syntactic features that also scale with paranoia. Results indicate that a personality trait can act as an intrinsic "prime," yielding different neural and behavioral responses to the same stimulus across individuals. PMID- 29795118 TI - Profiling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils. AB - Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop effective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, flow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset-selective biomarkers associated with tonsillar cancer. We describe, for the first time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c-CD141- myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specific for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of effector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by different DC subsets in malignant tonsils and confirm expression of CD206/MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer. PMID- 29795119 TI - Asymmetric hemisphere activation in tenderness: evidence from EEG signals. AB - Emotions are processed asymmetrically by the human brain. Frontal alpha asymmetry (FAA) as measured by electroencephalographic (EEG) power in the alpha band (8-13 Hz), is a sensitive indicator of asymmetric brain activity in the frontal cortex. The current study aimed to analyze the frontal EEG asymmetries in terms of valence and motivational direction. We presented 37 participants with three film excerpts that were selected from the standard emotional film database to elicit three target emotions: tenderness, anger, and neutrality. Participants' self reports on their induced emotional responses and EEG signals were recorded and analyzed. The results showed that individuals displayed lower alpha power in the left hemisphere than the right hemisphere when they were watching a tender film, indicating that tenderness was positive and related to approach motivation. In contrast, when watching an angry movie, participants showed higher alpha power in the left hemisphere than the right hemisphere, suggesting that anger was negative and associated with withdrawal motivation. These findings help to link positive and approach-motivated tenderness with greater left hemispheric activation and state-anger with greater right hemispheric activation through the analysis of FAA. PMID- 29795117 TI - C151 in KEAP1 is the main cysteine sensor for the cyanoenone class of NRF2 activators, irrespective of molecular size or shape. AB - Numerous small molecules (termed inducers), many of which are electrophiles, upregulate cytoprotective responses and inhibit pro-inflammatory pathways by activating nuclear factor-erythroid 2 p45-related factor 2 (NRF2). Key to NRF2 activation is the ability to chemically modifying critical sensor cysteines in the main negative regulator of NRF2, Kelch-like ECH-associated protein 1 (KEAP1), of which C151, C273 and C288 are best characterized. This study aimed to establish the requirement for these cysteine sensor(s) for the biological activities of the most potent NRF2 activators known to date, the cyclic cyanoenones, some of which are in clinical trials. It was found that C151 in KEAP1 is the main cysteine sensor for this class of inducers, irrespective of molecular size or shape. Furthermore, in primary macrophage cells expressing C151S mutant KEAP1, at low concentrations, the tricyclic cyanoenone TBE-31 is inactive as an activator of NRF2 as well as an inhibitor of lipopolysaccharide stimulated gene expression of the pro-inflammatory cytokines IL6 and IL1beta. However, at high inducer concentrations, NRF2 activation proceeds in the absence of C151, albeit at a lower magnitude. Our findings highlight the intrinsic flexibility of KEAP1 and emphasize the critical importance of establishing the precise dose of NRF2 activators for maintaining on-target selectivity. PMID- 29795120 TI - Antimicrobial and anti-biofilm activity of hexadentated macrocyclic complex of copper (II) derived from thiosemicarbazide against Staphylococcus aureus. AB - Multidrug-resistant pathogens causing nosocomial and community acquired infections delineate a significant threat to public health. It had urged to identify new antimicrobials and thus, generated interest in studying macrocyclic metal complex, which has been studied in the past for their antimicrobial activity. Hence, in the present study, we have evaluated the antimicrobial activity of the hexadentated macrocyclic complex of copper (II) (Cu Complex) derived from thiosemicarbazide against Gram-positive and Gram-negative bacteria. We observed increased susceptibility against standard isolates of Staphylococcus aureus with a minimum inhibitory concentration (MIC) range of 6.25 to 12.5 MUg/mL. Similar activity was also observed towards methicillin resistant and sensitive clinical isolates of S. aureus from human (n = 20) and animal (n = 20) infections. The compound has rapid bactericidal activity, and we did not observe any resistant mutant of S. aureus. The compound also exhibited antibiofilm activity and was able to disrupt pre-formed biofilms. Cu complex showed increased susceptibility towards intracellular S. aureus and was able to reduce more than 95% of the bacterial load at 10 MUg/mL. Overall, our results suggest that Cu complex with its potent anti-microbial and anti-biofilm activity can be used to treat MRSA infections and evaluated further clinically. PMID- 29795121 TI - Extraction and quantification of biofilm bacteria: Method optimized for urinary catheters. AB - Bacterial biofilms are responsible for the failure of many medical devices such as urinary catheters and are associated with many infectious and non-infectious complications. Preclinical and clinical evaluation of novel catheter coatings to prevent these infections needs to accurately quantify the bacterial load in the biofilm in vitro and ex vivo. There is currently no uniform gold standard for biofilm quantification for different surfaces and established biofilms. We have tried to establish a simple, accurate and reproducible method for extraction and measurement of biofilm bacteria on indwelling catheters, using a combination of vortexing and sonication. We demonstrate the usefulness of this method for catheters of different sizes - 3 Fr to 14 Fr - in vitro, in murine and porcine models, and indwelling in human clinical subjects. We also demonstrate consistent results with complex and polymicrobial biofilms. We believe that this standardized reproducible method will assist the assessment of biofilms in general and urological devices in particular in efforts to harness novel technologies to prevent healthcare associated infections. PMID- 29795122 TI - Biochar Impacts on Soil Silicon Dissolution Kinetics and their Interaction Mechanisms. AB - Effects of biochars on soil silicon dissolution kinetics remain unaddressed. Si rich rice husk (RH) and rice straw (RS), and Si-deficient wood sawdust (WB) and orange peel (OP) were applied to prepare biochars at 300-700 degrees C. The silicon dissolution of Si-rich biochars was relatively high in comparison with Si deficient biochars, and increased with the pyrolysis temperature. The mechanism of silicon release is suggested to be controlled by a protective carbon-silicon interaction, as accompanied by carbon release. After mixing with soil, the addition of Si-rich biochar leads up to 72.7-121% improvement in silicon dissolution in a high-silicon soil (HSS) compared to 147-243% improvement in a low-silicon soil (LSS). The total cumulative amount of silicon dissolved decreased compared to the theoretical value due to the adsorption of silicic acid by the biochar. The addition of WB700 or OP700 as Si-deficient biochars leads to a cumulative Si dissolution decrease of 15.7 and 12.1%, respectively. The adsorption of silicic acid in the biochar and the protection of soil dissolved Fe make biochar a reservoir of soil silicon. Thus, Si-rich biochar could serve as a source of Si with slow release, while Si-deficient biochar could serve as an extra Si sink in agricultural paddy soil. PMID- 29795125 TI - Towards a complete map of the human long non-coding RNA transcriptome. AB - Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single gene to genome-wide scales and from basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding RNAs (lncRNAs), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of lncRNAs expressed throughout a human lifetime. PMID- 29795126 TI - Estimating heritability without genetic testing. PMID- 29795124 TI - Direct observation of high spin polarization in Co2FeAl thin films. AB - We have studied the Co2FeAl thin films with different thicknesses epitaxially grown on GaAs (001) by molecular beam epitaxy. The magnetic properties and spin polarization of the films were investigated by in-situ magneto-optic Kerr effect (MOKE) measurement and spin-resolved angle-resolved photoemission spectroscopy (spin-ARPES) at 300 K, respectively. High spin polarization of 58% (+/-7%) was observed for the film with thickness of 21 unit cells (uc), for the first time. However, when the thickness decreases to 2.5 uc, the spin polarization falls to 29% (+/-2%) only. This change is also accompanied by a magnetic transition at 4 uc characterized by the MOKE intensity. Above it, the film's magnetization reaches the bulk value of 1000 emu/cm3. Our findings set a lower limit on the thickness of Co2FeAl films, which possesses both high spin polarization and large magnetization. PMID- 29795123 TI - Randomised Controlled Clinical Trial Investigating The Impact of Implementation Planning on Behaviour Related to The Diet. AB - There is a perceived gap between dietary advice given by health practitioners and adherence to the advice by patients. We investigated whether a behaviour change technique (implementation-planning) was more effective than standard-of-care diet advice at reducing dietary acid intake using quantitative erosive tooth wear progression as an objective clinical outcome. This study was a randomised controlled, double-blind, single-centre clinical trial in the UK. Participants (n = 60) with high dietary acid intake (>=2 daily), were recruited and randomly assigned (1:1) to receive either implementation-planning or standard-of-care diet advice in a single clinical session. Questionnaires and impressions were taken at baseline and 6 months later. Dental casts were scanned using laser profilometry and superimposed using surface-matching software. Data were analysed per protocol and intention-to-treat using independent t-tests and Mann-Whitney tests. The intervention group reduced their dietary acid intake between meals to 1 intake per day compared to 2 intakes per day for the controls and demonstrated reduced dental hard tissue volume loss (-0.00 mm3 (SD = 0.01)) compared to controls ( 0.07 mm3 (SD 0.17)), p = 0.049. This paper supports the use of implementation planning in clinical practice and presents a non-invasive method of intervention assessment in behaviour change. Larger trials are needed to confirm the generalisability of results. PMID- 29795127 TI - Characterization of smooth muscle cells from human atherosclerotic lesions and their responses to Notch signaling. AB - Atherosclerosis is the most common cause of heart disease and stroke. The use of animal models has advanced our understanding of the molecular signaling that contributes to atherosclerosis. Further understanding of this degenerative process in humans will require human tissue. Plaque removed during endarterectomy procedures to relieve arterial obstructions is usually discarded, but can be an important source of diseased cells. Resected tissue from carotid and femoral endarterectomy procedures were compared with carotid arteries from donors with no known cardiovascular disease. Vascular smooth muscle cells (SMC) contribute to plaque formation and may determine susceptibility to rupture. Notch signaling is implicated in the progression of atherosclerosis, and plays a receptor-specific regulatory role in SMC. We defined protein localization of Notch2 and Notch3 within medial and plaque SMC using immunostaining, and compared Notch2 and Notch3 levels in total plaques with whole normal arteries using immunoblot. We successfully derived SMC populations from multiple endarterectomy specimens for molecular analysis. To better define the protein signature of diseased SMC, we utilized sequential window acquisition of all theoretical spectra (SWATH) proteomic analysis to compare normal carotid artery SMC with endarterectomy derived SMC. Similarities in protein profile and differentiation markers validated the SMC identity of our explants. We identified a subset of differentially expressed proteins that are candidates as functional markers of diseased SMC. To understand how Notch signaling may affect diseased SMC, we performed Jagged1 stimulation of primary cultures. In populations that displayed significant growth, Jagged1 signaling through Notch2 suppressed proliferation; cultures with low growth potential were non-responsive to Jagged1. In addition, Jagged1 did not promote contractile smooth muscle actin nor have a significant effect on the mature differentiated phenotype. Thus, SMC derived from atherosclerotic lesions show distinct proteomic profiles and have altered Notch signaling in response to Jagged1 as a differentiation stimulus, compared with normal SMC. PMID- 29795128 TI - An optical coherence tomography study of residual subfoveal fluid after successful pars plana vitrectomy in patients with diabetic tractional macular detachment. AB - PURPOSE: To analyze the prevalence of residual subfoveal fluid (RSF) after pars plana vitrectomy in patients with proliferative diabetic retinopathy complicated by tractional detachment of the macula and the effect of RSF on the postoperative visual outcome. METHODS: This study was a prospective observational case study of the optical coherence tomography (OCT) records of 23 patients (24 eyes) with macula-off diabetic tractional retinal detachment (TRD) who underwent successful 23-gauge pars plana vitrectomy between July 2012 and December 2015. RESULTS: The prevalence of RSF on OCT examination was 100% at 1 and 2 months, 91.7% at 3 months, 70.8% at 6 months, 25.0% at 9 months and 4.2% at 12 months after surgery (p < 0.001). Internal drainage of subretinal fluid (SRF) during primary surgery was performed in 13 (54.2%) eyes. The significant risk factor that was predictive of long-standing RSF was non-drainage of SRF (p = 0.04). CONCLUSION: Persistent RSF is a common OCT finding after clinically successful vitrectomy surgery for the treatment of macula-off diabetic tractional retinal detachment. Internal drainage of SRF with active aspiration can be attempted if intraoperative breaks are found or if faster recovery is required. To date, observation seems to be the best option. PMID- 29795130 TI - Electric cataracts: a cause of bilateral blindness in Kashmir. PMID- 29795129 TI - Involvement of ciliary neurotrophic factor in early diabetic retinal neuropathy in streptozotocin-induced diabetic rats. AB - OBJECTIVE: Ciliary neurotrophic factor (CNTF) has been evaluated as a candidate therapeutic agent for diabetes and its neural complications. However, its role in diabetic retinopathy has not been fully elucidated. METHODS: This is a randomized unblinded animal experiment. Wistar rats with streptozocin (STZ)-induced diabetes were regularly injected with CNTF or vehicle control in their vitreous bodies beginning at 2 weeks after STZ injection. A total of five injections were used. In diabetic rats, the levels of CNTF and neurotrophin-3 (NT-3) were evaluated by enzyme-linked immunosorbent assays (ELISA) and real-time PCR. The abundance of tyrosine hydroxylase (TH) and beta-III tubulin was detected by western blot. Transferase-mediated dUTP nick-end labeling staining (TUNEL) was used to detect cell apoptosis in the retinal tissue. The activation of caspase-3 was also measured. RESULTS: The protein and mRNA levels of CNTF in diabetic rat retinas were reduced compared to control rats. In addition, retinal ganglion cells (RGCs) and dopaminergic amacrine cells appeared to undergo degeneration in diabetic rat retinas, as revealed by transferase-mediated dUTP nick-end labeling staining (TUNEL). Tyrosine hydroxylase (TH) and beta-III tubulin protein levels also decreased significantly. Intraocular administration of CNTF rescued RGCs and dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of beta-III tubulin and TH expression, thus demonstrating its therapeutic potential. CONCLUSION: Our study suggests that early diabetic retinal neuropathy involves the reduced expression of CNTF and can be ameliorated by an exogenous supply of this neurotrophin. PMID- 29795131 TI - Publisher Correction: Identification of oral cancer related candidate genes by integrating protein-protein interactions, gene ontology, pathway analysis and immunohistochemistry. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29795133 TI - Specializations for reward-guided decision-making in the primate ventral prefrontal cortex. AB - The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC - the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) - and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision making. PMID- 29795132 TI - Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy. AB - Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury. PMID- 29795134 TI - Pharmacological actions of miltirone in the modulation of platelet function. AB - Salvia miltiorrhiza Bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play roles in anti-platelet activity. The aim of the present study was to investigate the effects and the underlying mechanism of miltirone, a lipophilic compound of Salvia miltiorrhiza Bunge. The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments. Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer. Clot retraction and spreading were imaged by digital camera and fluorescence microscope. Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone antithrombotic effect in vivo. To elucidate the mechanisms of anti-platelet activity of miltirone, flow cytometry and western blotting were performed. Miltirone (2, 4, 8 uM) was shown to suppress platelet aggregation, dense granule, and alpha granule secretion in a dose-dependent manner. Meanwhile, miltirone inhibited the clot retraction and spreading of washed platelets. It reduced the phosphorylation of PLCgamma2, PKC, Akt, GSK3beta and ERK1/2 in the downstream signal pathway of collagen receptor. It also reduced the phosphorylation of Src and FAK in the integrin alphaIIbbeta3-mediated "outside-in" signaling, while it did not suppress the phosphorylation of beta3. In addition, miltirone prolonged the occlusion time and reduced collagen/epinephrine-induced pulmonary thrombi. Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCgamma2/PKC/ERK1/2, PI3K/Akt, and Src/FAK signaling. Therefore, miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders. PMID- 29795135 TI - Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF kappaB and p38 MAPK signaling pathways in 5/6 nephrectomized rats. AB - Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy. However, there has been limited research regarding the effects of SAA and underlying mechanisms in chronic kidney disease (CKD). Here, we examined the effects and molecular mechanisms of SAA in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The rats were injected with SAA (2.5, 5, and 10 mg/kg per day, intraperitoneally (ip)) for 28 days. SAA dose-dependently lowered the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides in 5/6Nx rats. Histological examination revealed that SAA dose-dependently attenuated renal pathological lesions, evidenced by reduced renal tubulointerstitial fibrosis by decreasing the expression levels of tumor growth factor-beta1 and alpha-smooth muscle actin in 5/6Nx rats. Moreover, SAA dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, subsequently attenuating the secretion of tumor necrosis factor-alpha and interleukin-1beta and inhibiting the expression of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in kidneys of 5/6Nx rats. The above results were consistent with those obtained in lipopolysaccharide induced HK-2 cells in vitro (a recognized in vitro inflammatory model). In conclusion, our results demonstrated that SAA effectively attenuates kidney injury in 5/6Nx rats. The therapeutic effects of SAA on kidney injury can be attributed to its anti-inflammatory activities through inhibition of the activation of the NF-kappaB and p38 MAPK signaling pathways. PMID- 29795136 TI - Metabolism, pharmacokinetics, and hepatic disposition of xanthones and saponins on Zhimu treatments for exploratively interpreting the discrepancy between the herbal safety and timosaponin A3-induced hepatotoxicity. AB - Timosaponin A3, a saponin in Zhimu, elicited hepatotoxicity via oxidative stress. However, the clinical medication of Zhimu has been historically regarded as safe, probably associated with the antioxidants it contains. However, the related information on the in vivo levels of timosaponin A3 and antioxidants remained unclear on Zhimu treatments. Therefore, a combination of the in vitro metabolism, including microbiota-mediated and liver-mediated metabolism, and in vivo pharmacokinetics and hepatic disposition, was conducted for three xanthones (neomangiferin, mangiferin, and norathyriol) and three saponins (timosaponin B2, timosaponin B3, and timosaponin A3) on Zhimu treatments. Consequently, following oral administration of Zhimu decoction to rats, those saponins and xanthones were all observed in the plasma with severe liver first-pass effect, where mangiferin was of the maximum exposure. Despite the ignorable content in the herb, timosaponin A3 elicited sizable hepatic exposure as the microbiota-mediated metabolite of saponins in Zhimu. The similar phenomenon also occurred to norathyriol, the microbiota-mediated metabolite of xanthones. However, the major prototypes in Zhimu were of limited hepatic exposure. We deduced the hepatic collection of norathyriol, maximum circulating levels of mangiferin, and timosaponin B2 and mangiferin interaction may directly or indirectly contribute to the whole anti-oxidation of Zhimu, and then resisted the timosaponin A3 induced hepatotoxicity. Thus, our study exploratively interpreted the discrepancy between herbal safety and timosaponin A3-induced hepatotoxicity. However, given the considerable levels and slow eliminated rate of timosaponin A3 in the liver, more attention should be paid to the safety on the continuous clinical medication of Zhimu in the future. PMID- 29795138 TI - Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance. AB - Although rare variant C1Q deficiency was identified as causative risk for systemic lupus erythematosus (SLE), there are limited and inconsistent reports regarding the common polymorphisms of C1Q genes in SLE susceptibility. Furthermore, there are no reports concerning polymorphisms of C1S, C1R, and C1RL and whether they confer susceptibility to SLE. We therefore evaluated 22 SNPs across six C1-complex genes in two independent case-control cohorts, and identified four novel SNPs that confer protection from SLE. The four SNPs are all located in C1Q. Particularly, the variant rs653286 displayed an independent reduced risk on SLE susceptibility (OR 0.75, P = 2.16 * 10-3) and anti-dsDNA antibodies (OR 0.68, P = 0.024). By bioinformatics analysis, SNPs rs653286 and rs291985 displayed striking cis-eQTL effects on C1Q genes expression. Individuals homozygous for the 'protective' allele at four SNPs had significantly higher levels of serum C1q (rs680123-rs682658: P = 0.0022; rs653286-rs291985: P = 0.0076). To our knowledge, this is the first study to demonstrate that only C1Q polymorphisms are associated with SLE. The C1Q SNP rs653286 confers an independent protective effect on SLE susceptibility and affects transcript abundance. PMID- 29795137 TI - Microfluidic cell sorting: Towards improved biocompatibility of extracorporeal lung assist devices. AB - Extracorporeal lung assist technology is one of the last options in critical care medicine to treat patients suffering from severe oxygenation and decarboxylation disorders. Platelet activation along with the consequent thrombus formation is a potentially life-threatening complication of this technique. To avoid platelet dependent clot formation, this study aims at developing a microfluidic cell sorting chip that can bypass platelets prior to the membrane oxygenator of the extracorporeal lung assist device. The cell sorting chips were produced by maskless dip-in laser lithography, followed by soft lithography replication using PDMS. Citrated porcine whole blood with a clinically relevant haematocrit of 17% was used for the cell sorting experiments involving three different blood flow rates. The joint effects of flow focusing and hydrodynamic lifting forces within the cell sorting chip resulted in a reduction of up to 57% of the baseline platelet count. This cell sorting strategy is suitable for the continuous and label-free separation of red blood cells and platelets and is potentially applicable for increasing the biocompatibility and lifetime of current extracorporeal lung assist devices. PMID- 29795139 TI - Docetaxel enhances lysosomal function through TFEB activation. AB - Docetaxel is an effective and commonly used chemotherapeutic drug for cancer. Autophagy has been reported to be involved in the anticancer mechanism of docetaxel. However, the effect of docetaxel on lysosomal function remains elusive. In the present study, we first found that docetaxel treatment enhances autophagic flux in different cancer cells. Moreover, docetaxel treatment activates lysosomal function and promotes its fusion with autophagosome. Second, doctaxel treatment activates TFEB (transcription factor EB), a key nuclear transcription factor in control of lysosome biogenesis and function. We found that docetaxel promotes TFEB nuclear translocation and increases its transcriptional activity while knockdown of TFEB impairs lysosomal activation by docetaxel. Thirdly, TFEB activation by docetaxel is mediated by ROS (reactive oxygen species) generation and scavenging of ROS suppresses TFEB activity and lysosomal function in docetaxel-treated cells. Finally, inhibition of lysosomal function leads to increased docetaxel-induced cell death, suggesting that lysosomal activation protects against docetaxel-mediated apoptosis. Taken together, our results provide novel insights into the regulatory mechanisms of docetaxel on lysosomes, which could facilitate the development of novel potential cancer therapeutic agents via lysosomal inhibition. PMID- 29795140 TI - The microbiome in prostate inflammation and prostate cancer. AB - BACKGROUND: The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti carcinogenic xenobiotic metabolism, and treatment response. METHODS: We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer. RESULTS: Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease. CONCLUSIONS: In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved. PMID- 29795141 TI - PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study. AB - BACKGROUND: The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. METHODS: A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. RESULTS: A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). CONCLUSIONS: Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia. PMID- 29795143 TI - What's the appropriate adjustment when an approved drug is in short supply? PMID- 29795144 TI - Considering animal welfare with scientific justification in mind. PMID- 29795142 TI - Serum cholesterol levels and tumor growth in a PTEN-null transgenic mouse model of prostate cancer. AB - BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cholesterol levels on prostate tumor development and growth. We hypothesized that serum cholesterol reduction would lower tumor androgens and slow prostate cancer growth. METHODS: PTENloxP/loxP-Cre+ mice consuming ad libitum high fat, high cholesterol diets (40% fat, 1.25% cholesterol) were randomized after weaning to receive the cholesterol uptake inhibitor, ezetimibe (30 mg/kg/day), or no intervention, and sacrificed at 2, 3, or 4 months of age. Serum cholesterol and testosterone were measured by ELISA and intraprostatic androgens by mass spectrometry. Prostate histology was graded, and proliferation and apoptosis in tumor epithelium and stroma was assessed by Ki67 and TUNEL, respectively. RESULTS: Ezetimibe-treated mice had lower serum cholesterol at 4 months (p = 0.031). Serum cholesterol was positively correlated with prostate weight (p = 0.033) and tumor epithelial proliferation (p = 0.069), and negatively correlated with tumor epithelial apoptosis (p = 0.004). Serum cholesterol was unrelated to body weight (p = 0.195). Tumor stromal cell proliferation was reduced in the ezetimibe group (p = 0.010). Increased serum cholesterol at 4 months was associated with elevated intraprostatic DHEA, testosterone, and androstenedione (p = 0.043, p = 0.074, p = 0.031, respectively). However, cholesterol reduction did not significantly affect adenocarcinoma development at 2, 3, or 4 months of age (0, 78, and 100% in ezetimibe-treated vs. 0, 80, and 100% in mice not receiving ezetimibe). CONCLUSIONS: Though serum cholesterol reduction did not significantly affect the rate of adenocarcinoma development in the PTEN-null transgenic mouse model of prostate cancer, it lowered intraprostatic androgens and slowed tumor growth. These findings support a role for serum cholesterol in promoting prostate cancer growth, potentially via enhanced tumor androgen signaling, and may provide new insight into cholesterol lowering interventions for prostate cancer treatment. PMID- 29795145 TI - Redirecting the request to the IACUC. PMID- 29795146 TI - Mapping brain activity to predict stress responses. PMID- 29795147 TI - Painless pain assessments with machine learning. PMID- 29795148 TI - These wild mice. PMID- 29795149 TI - Freed up to fly. PMID- 29795150 TI - An NHP for CCHF research. PMID- 29795151 TI - Placenta problems. PMID- 29795152 TI - Urban(e) is not necessarily better. PMID- 29795153 TI - Novel treatment for neuropathy. PMID- 29795154 TI - New neurological model. PMID- 29795155 TI - June Updates: People and Places. PMID- 29795156 TI - Extending lifespan without hunger. PMID- 29795157 TI - Achieving the desired outcome. PMID- 29795158 TI - The Drosophila model for microbiome research. AB - The gut microbiome is increasingly recognized to play an important role in shaping the health and fitness of animals, including humans. Drosophila is emerging as a valuable model for microbiome research, combining genetic and genomic resources with simple protocols to manipulate the microbiome, such that microbiologically sterile flies and flies bearing a standardized microbiota can readily be produced in large numbers. Studying Drosophila has the potential to increase our understanding of how the microbiome influences host traits, and allows opportunities for hypothesis testing of microbial impacts on human health. Drosophila is being used to investigate aspects of host-microbe interactions, including the metabolism, the immune system and behavior. Drosophila offers a valuable alternative to rodent and other mammalian models of microbiome research for fundamental discovery of microbiome function, enabling improved research cost effectiveness and benefits for animal welfare. PMID- 29795159 TI - A Word from OLAW. PMID- 29795160 TI - Addressing administrative burden: a primer for submitting comments to the USDA and OLAW. PMID- 29795161 TI - Rodents move towards the Disease Ontology. PMID- 29795163 TI - Tracking development with DNA 'scars'. PMID- 29795164 TI - DIY goes in vivo. PMID- 29795165 TI - Insulin resistance grows in the dark. PMID- 29795166 TI - Publisher Correction: Using high-amplitude and focused transcranial alternating current stimulation to entrain physiological tremor. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29795167 TI - Neuromolecular basis of faded perception associated with unreality experience. AB - Perceptual changes in shape, size, or color are observed in patients with derealization symptoms; however, the underlying neural and molecular mechanisms are not well understood. The current study explored the relationship between neural activity associated with altered colorfulness perception assessed by fMRI and striatal dopamine D2 receptor availability measured by [11C]raclopride PET in healthy participants. Inside an fMRI scanner, participants performed the saturation adaptation task, where they rated how much vivid/faded visual objects looked like real/unreal ones using a visual analog scale. We found that participants experienced greater unreality when they perceived fadedness than vividness despite physically identical saturation. The combined fMRI and PET analyses revealed that the faded perception-related activities of the dorsolateral prefrontal and parietal cortex were positively correlated with striatal D2 receptor availability. This finding may help to understand the neuromolecular mechanisms of faded perception associated with feeling unreal in derealization symptoms. PMID- 29795169 TI - Associations between time since onset of injury and participation in Dutch people with long-term spinal cord injury. AB - STUDY DESIGN: Multicentre cross-sectional study. OBJECTIVES: To describe relationships between time since injury (TSI) and participation in individuals with tetraplegia and paraplegia. SETTING: Community sample from the Netherlands METHODS: Individuals (N = 265) aged 28-65 years, living with spinal cord injury (SCI) for >=10 years, age at injury between 18-35 years and using a wheelchair for everyday mobility in three TSI strata: 10-19, 20-29, and >=30 years post injury. The Utrecht Scale for Evaluation of Rehabilitation-Participation (USER Participation) was used, which consists of three scales: Frequency (including subscales for Productive, Leisure, and Social activities), Restrictions, and Satisfaction. Linear regression analyses were used to study the effect of TSI on participation, and to adjust for personal and lesion characteristics, for individuals with tetraplegia and paraplegia separately. RESULTS: Mean age was 48.4 years, with a mean TSI of 24 years. About 73.6% were male, 40.4% had tetraplegia and 81.9% had a motor complete injury. In individuals with tetraplegia (N = 107), longer TSI was independently associated with lower scores on the Frequency scale (p = 0.025) and the subscale frequency of Leisure activities (p = 0.004). In individuals with paraplegia (N = 158), longer TSI was independently associated with lower scores on the subscale frequency of Productive activities (p = 0.006). TSI was not associated with participation Restrictions and Satisfaction with participation. CONCLUSIONS: Longer TSI is associated with a reduced frequency of participation in individuals with long term SCI. Interestingly, this negative association is not accompanied by a similar association in the person's experience of participation. PMID- 29795168 TI - Extremely stable graphene electrodes doped with macromolecular acid. AB - Although conventional p-type doping using small molecules on graphene decreases its sheet resistance (Rsh), it increases after exposure to ambient conditions, and this problem has been considered as the biggest impediment to practical application of graphene electrodes. Here, we report an extremely stable graphene electrode doped with macromolecular acid (perfluorinated polymeric sulfonic acid (PFSA)) as a p-type dopant. The PFSA doping on graphene provides not only ultra high ambient stability for a very long time (> 64 days) but also high chemical/thermal stability, which have been unattainable by doping with conventional small-molecules. PFSA doping also greatly increases the surface potential (~0.8 eV) of graphene, and reduces its Rsh by ~56%, which is very important for practical applications. High-efficiency phosphorescent organic light-emitting diodes are fabricated with the PFSA-doped graphene anode (~98.5 cd A-1 without out-coupling structures). This work lays a solid platform for practical application of thermally-/chemically-/air-stable graphene electrodes in various optoelectronic devices. PMID- 29795170 TI - A validity study of the Spanish-World Health Organization Quality of Life short version instrument in persons with traumatic spinal cord injury. AB - STUDY DESIGN: This was a psychometric study. OBJECTIVES: To determine the validity of the Spanish version of the World Health Organization Quality of Life instrument (WHOQOL-BREF) for its use in persons with traumatic spinal cord injury and, as secondary objectives, to correlate the results with variables such as functional status, psychological well-being, and social support. SETTING: Spinal Cord Injury Unit, Complejo Hospitalario Universitario de A Coruna, Galicia (Spain). METHODS: Fifty-four people with spinal cord injury were enrolled in this study. Relevant variables were analyzed based on the scores reported by each participant in the Spanish versions of the WHOQOL-BREF questionnaire, the Spinal Cord Independence Measure, the Hospital Anxiety and Depression Scale (HADS), and the Duke-UNC Functional and Social Support Questionnaire. Both parametric and non parametric tests were used to compare various variables. The instrument's internal consistency and test-retest reliability were also confirmed. RESULTS: The mean scores of each domain of the WHOQOL-BREF were lower, but nonsignificant, among people who need help to perform activities of daily living. The correlation between the scores obtained in the "Psychological" domain and the items of the HADS scale was significant. Significant differences were also observed when comparing the results of the "Social relationships" and "Environment" domains among people with low scores in the Duke questionnaire. Both an adequate consistency (Cronbach's alpha: 0.887) and test-retest reliability were demonstrated. CONCLUSION: The Spanish version of the WHOQOL-BREF questionnaire is useful and reliable to evaluate the quality of life of persons with spinal cord injuries in our population of Spanish-speaking people. PMID- 29795171 TI - Time-dependent changes in paw carrageenan-induced inflammation above and below the level of low thoracic spinal cord injury in rats. AB - STUDY DESIGN: This was an animal study. OBJECTIVES: Local inflammation is attenuated below high thoracic SCI, where innervation of major lymphoid organs is involved. However, whether inflammatory responses are affected after low thoracic SCI, remains undetermined. The aim of this study was to characterize the influence of low thoracic SCI on carrageenan-induced paw swelling in intact and paralyzed limbs, at acute and subacute stages. SETTING: University and hospital based research center, Mexico City, Mexico. METHODS: Rats received a severe contusive SCI at T9 spinal level or sham injury. Then, 1 and 15 days after lesion, carrageenan or vehicle was subcutaneously injected in forelimb and hindlimb paws. Paw swelling was measured over a 6-h period using a plethysmometer. RESULTS: Swelling increased progressively reaching the maximum 6 h post-carrageenan injection. Swelling increase in sham-injured rats was approximately 130% and 70% compared with baseline values of forelimbs and hindlimbs, respectively. Paws injected with saline exhibited no measurable swelling. Carrageenan-induced paw swelling 1-day post-SCI was suppressed in both intact and paralyzed limbs. Fifteen days post-injury, the swelling response to carrageenan was completely reestablished in forelimbs, whereas in hindlimbs it remained significantly attenuated compared with sham-injured rats. CONCLUSIONS: SCI at low spinal level affects the induced swelling response in a different way depending on both, the neurological status of challenged regions and the stage of injury. These findings suggest that neurological compromise of the main immunological organs is not a prerequisite for the local swelling response to be affected after injury. PMID- 29795172 TI - Effects of moderate- and high-intensity aerobic training program in ambulatory subjects with incomplete spinal cord injury-a randomized controlled trial. AB - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To investigate if high intensity interval training (HIIT) exhibits a higher increase in physical capacity and activity levels compared to moderate-intensity training (MIT) and treatment as usual. SETTING: Sunnaas Rehabilitation Hospital. METHODS: Thirty ambulatory participants with incomplete spinal cord injury (SCI) were recruited at discharge from inpatient rehabilitation. Two intervention groups performed a 12-week individual training program at home by walking or running, depending on their physical ability. The MIT group was instructed to exercise three times a week at 70% of maximal heart rate (HRmax), while the HIIT group was instructed to exercise twice a week at 85-95% of HRmax. The control group received treatment as usual. Pre- and post-tests consisted of maximal exercise testing on a treadmill (peak oxygen uptake (peak VO2)), a 6-min walking test (6MWT), and 7 days of continuously activity monitoring (total daily energy expenditure (TDEE) and daily number of steps). RESULTS: The HIIT, MIT, and control groups showed an increase in peak VO2 from pre- to post-test. However, no between-group difference in physical capacity (peak VO2 and 6MWT) and physical activity levels (TDEE and daily number of steps) were found between these groups. CONCLUSIONS: Performing HIIT did not exhibit a greater increase in physical capacity and activity levels than performing MIT or "treatment as usual" in ambulatory participants with SCI. Further studies are needed to elucidate both short- and long-term effects of HIIT and MIT in this SCI subpopulation. PMID- 29795174 TI - Borderline personality disorder. PMID- 29795173 TI - Development of an International Canine Spinal Cord Injury observational registry: a collaborative data-sharing network to optimize translational studies of SCI. AB - STUDY DESIGN: Prospective cross-sectional cohort study. OBJECTIVES: The canine spontaneous model of spinal cord injury (SCI) is as an important pre-clinical platform as it recapitulates key facets of human injury in a naturally occurring context. The establishment of an observational canine SCI registry constitutes a key step in performing epidemiologic studies and assessing the impact of therapeutic strategies to enhance translational research. Further, accumulating information on dogs with SCI may contribute to current "big data" approaches to enhance understanding of the disease using heterogeneous multi-institutional, multi-species datasets from both pre-clinical and human studies. SETTING: Multiple veterinary academic institutions across the United States and Europe. METHODS: Common data elements recommended for experimental and human SCI studies were reviewed and adapted for use in a web-based registry, to which all dogs presenting to member veterinary tertiary care facilities were prospectively entered over ~1 year. RESULTS: Analysis of data accumulated during the first year of the registry suggests that 16% of dogs with SCI present with severe, sensorimotor-complete injury and that 15% of cases are seen by a tertiary care facility within 8 h of injury. Similar to the human SCI population, 34% were either overweight or obese. CONCLUSIONS: Severity of injury and timing of presentation suggests that neuroprotective studies using the canine clinical model could be conducted efficiently using a multi-institutional approach. Additionally, pet dogs with SCI experience similar comorbidities to people with SCI, in particular obesity, and could serve as an important model to evaluate the effects of this condition. PMID- 29795175 TI - Monitoring of asparagine depletion and anti-L-asparaginase antibodies in adult acute lymphoblastic leukemia treated in the pediatric-inspired GRAALL-2005 trial. PMID- 29795176 TI - Reflective grating-coupled structure improves the detection efficiency of THz array detectors. AB - A reflective grating-coupled structure on the silicon substrate was designed to improve the detection efficiency of terahertz detectors for the frequency ranging from 0.26 THz to 0.36 THz. By using finite difference time domain (FDTD) solutions, the simulation and optimized design of the grating-coupled structure were carried out. The results showed that the signal was effectively reflected and diffracted by the reflective grating-coupled structure which significantly enhanced the electric field in the place of the detector. The maximum electric field can be increased by 2.8 times than that of the Fabry-Perot resonator. To verify the design results, the reflective grating-coupled structure was applied in the preparation of the Nb5N6 array detector chip and compared with the Nb5N6 array detector chip with the F-P resonator. The results showed that the maximum voltage responsivity of the Nb5N6 detector with the reflective grating-coupled structure was 2 times larger than the Nb5N6 detector with the F-P resonator. It indicates that the reflective grating-coupled structure can efficiently improve the detection efficiency of THz detectors. PMID- 29795177 TI - Kondo effect and enhanced magnetic properties in gadolinium functionalized carbon nanotube supramolecular complex. AB - We report on the enhancement of magnetic properties of multiwalled carbon nanotubes (MWNTs) functionalized with a gadolinium based supramolecular complex. By employing a newly developed synthesis technique we find that the functionalization method of the nanocomposite enhances the strength of magnetic interaction leading to a large effective moment of 15.79 uB and non superparamagnetic behaviour unlike what has been previously reported. Saturating resistance at low temperatures is fitted with the numerical renormalization group formula verifying the Kondo effect for magnetic impurities on a metallic electron system. Magnetoresistance shows devices fabricated from aligned gadolinium functionalized MWNTs (Gd-Fctn-MWNTs) exhibit spin-valve switching behaviour of up to 8%. This study highlights the possibility of enhancing magnetic interactions in carbon systems through chemical modification, moreover we demonstrate the rich physics that might be useful for developing spin based quantum computing elements based on one-dimensional (1D) channels. PMID- 29795179 TI - Evolutionary genetics of personality in the Trinidadian guppy II: sexual dimorphism and genotype-by-sex interactions. AB - Sexual dimorphism in behaviour and personality has been identified in a number of species, but few studies have assessed the extent of shared genetic architecture across the sexes. Under sexually antagonistic selection, mechanisms are expected to evolve that reduce evolutionary conflict, resulting in genotype-by-sex (GxS) interactions. Here we assess the extent of sexual dimorphism in four risk-taking behaviour traits in the Trinidadian guppy, Poecilia reticulata, and apply a multivariate approach to test for GxS interactions. We also quantify the among individual and genetic covariances between personality and size and growth, which are known a priori to differ between the sexes. We found significant sexual dimorphism in three of the four behaviours, although rmf between sex-specific homologous traits was significantly <+1 for only one behaviour. Using multivariate models, we then estimated sex-specific genetic (co)variance matrices (G m and G f ) and tested for asymmetry of the cross-trait cross-sex genetic covariance structure (submatrix B). While G m and G f were not significantly different from each other overall, their respective leading eigenvectors were poorly aligned. Statistical support for asymmetry in B was found, but limited to a single trait pair for which the cross-sex covariances differed (i.e., COVA(m,f) ? COVA(f,m)). Thus, while single- and multi-trait perspectives evidence some GxS, the overall picture is one of similarity between the sexes in their genetic (co)variance structures. Our results suggest behavioural traits related to risk taking may lack the sex-specific genetic architecture for further dimorphism to evolve under what is hypothesised to be antagonistic selection. PMID- 29795178 TI - Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation. AB - Hydroformylation of 1,2-disubstituted alkenes usually occurs at the alpha position of the directing heteroatom such as oxygen atom and nitrogen atom. By contrast, to achieve hydroformylation on the beta position of the heteroatom is a tough task. Herein, we report the asymmetric rhodium-catalyzed hydroformylation of 1,2-disubstituted alkenylsilanes with excellent regioselectivity at the beta position (relative to the silicon heteroatom) and enantioselectivity. In a synthetic sense, we achieve the asymmetric hydroformylation on the beta position of the oxygen atom indirectly by using the silicon group as a surrogate for the hydroxyl. Density functional theory (DFT) calculations are carried out to examine energetics of the whole reaction path for Rh/YanPhos-catalyzed asymmetric hydroformylation and understand its regioselectivity and enantioselectivity. Our computational study suggests that the silicon group can activate the substrate and is critical for the regioselectivity. PMID- 29795180 TI - Out of Africa: demographic and colonization history of the Algerian mouse (Mus spretus Lataste). AB - North Africa is now recognized as a major area for the emergence and dispersal of anatomically modern humans from at least 315 kya. The Mediterranean Basin is thus particularly suited to study the role of climate versus human-mediated changes on the evolutionary history of species. The Algerian mouse (Mus spretus Lataste) is an endemic species from this basin, with its distribution restricted to North Africa (from Libya to Morocco), Iberian Peninsula and South of France. A rich paleontological record of M. spretus exists in North Africa, suggesting hypotheses concerning colonization pathways, and the demographic and morphologic history of this species. Here we combined genetic (3 mitochondrial DNA loci and 18 microsatellites) and climatic niche modeling data to infer the evolutionary history of the Algerian mouse. We collected 646 new individuals in 51 localities. Our results are consistent with an anthropogenic translocation of the Algerian mouse from North Africa to the Iberian Peninsula via Neolithic navigators, probably from the Tingitane Peninsula. Once arrived in Spain, suitable climatic conditions would then have favored the dispersion of the Algerian mice to France. The morphological differentiation observed between Spanish, French and North African populations could be explained by a founder effect and possibly local adaptation. This article helps to better understand the role of climate versus human-mediated changes on the evolutionary history of mammal species in the Mediterranean Basin. PMID- 29795181 TI - Low doses of bioherbicide favour prion aggregation and propagation in vivo. AB - Public concerns over the use of synthetic pesticides are growing since many studies have shown their impact on human health. A new environmental movement in occidental countries promoting an organic agriculture favours the rebirth of botanical pesticides. These products confer an effective alternative to chemical pesticides such as glyphosate. Among the biopesticides, the alpha-terthienyls found in the roots of Tagetes species, are powerful broad-spectrum pesticides. We found that an alpha-terthienyl analogue with herbicidal properties, called A6, triggers resistant SDS oligomers of the pathogenic prion protein PrPSc (rSDS PrPSc) in cells. Our main question is to determine if we can induce those rSDS PrPSc oligomers in vitro and in vivo, and their impact on prion aggregation and propagation. Using wild-type mice challenged with prions, we showed that A6 accelerates or slows down prion disease depending on the concentration used. At 5 mg/kg, A6 is worsening the pathology with a faster accumulation of PrPSc, reminiscent to soluble toxic rSDS-PrPSc oligomers. In contrast, at 10 and 20 mg/kg of A6, prion disease occurred later, with less PrPSc deposits and with rSDS PrPSc oligomers in the brain reminiscent to non-toxic aggregates. Our results are bringing new openings regarding the impact of biopesticides in prion and prion like diseases. PMID- 29795183 TI - Author Correction: Transcriptome profiling of mouse colonic eosinophils reveals a key role for eosinophils in the induction of s100a8 and s100a9 in mucosal healing. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29795182 TI - Conserved RNA binding activity of a Yin-Yang 1 homologue in the ova of the purple sea urchin Strongylocentrotus purpuratus. AB - Yin-Yang 1 (YY1) is a highly conserved transcription factor possessing RNA binding activity. A putative YY1 homologue was previously identified in the developmental model organism Strongylocentrotus purpuratus (the purple sea urchin) by genomic sequencing. We identified a high degree of sequence similarity with YY1 homologues of vertebrate origin which shared 100% protein sequence identity over the DNA- and RNA-binding zinc-finger region with high similarity in the N-terminal transcriptional activation domain. SpYY1 demonstrated identical DNA- and RNA-binding characteristics between Xenopus laevis and S. purpuratus indicating that it maintains similar functional and biochemical properties across widely divergent deuterostome species. SpYY1 binds to the consensus YY1 DNA element, and also to U-rich RNA sequences. Although we detected SpYY1 RNA-binding activity in ova lysates and observed cytoplasmic localization, SpYY1 was not associated with maternal mRNA in ova. SpYY1 expressed in Xenopus oocytes was excluded from the nucleus and associated with maternally expressed cytoplasmic mRNA molecules. These data demonstrate the existence of an YY1 homologue in S. purpuratus with similar structural and biochemical features to those of the well studied vertebrate YY1; however, the data reveal major differences in the biological role of YY1 in the regulation of maternally expressed mRNA in the two species. PMID- 29795184 TI - Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes. AB - Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance. PMID- 29795185 TI - Regulation of filial imprinting and structural plasticity by mTORC1 in newborn chickens. AB - Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling leads to memory deficits and abnormal social behaviors in adults. However, whether mTORC1 is involved in critical periods of early learning remains largely unexplored. Our study addressed this question by investigating imprinting, a form of learning constrained to a sensitive period that supports filial attachment, in newborn chickens. Imprinting to virtual objects and sounds was assessed after acute manipulations of mTORC1. To further understand the role of mTORC1 during the critical period, structural plasticity was analyzed using DiOlistic labeling of dendritic spines. We found that mTORC1 is required for the emergence of experience-dependent preferences and structural plasticity within brain regions controlling behavior. Furthermore, upon critical period closure, pharmacological activation of the AKT/mTORC1 pathway was sufficient to rescue imprinting across sensory modalities. Thus, our results uncover a novel role of mTORC1 in the formation of imprinted memories and experience-dependent reorganization of neural circuits during a critical period. PMID- 29795188 TI - Retinopathy prevented by altering the microbiota. PMID- 29795186 TI - Protein polarization driven by nucleoid exclusion of DnaK(HSP70)-substrate complexes. AB - Many bacterial proteins require specific subcellular localization for function. How Escherichia coli proteins localize at one pole, however, is still not understood. Here, we show that the DnaK (HSP70) chaperone controls unipolar localization of the Shigella IpaC type III secretion substrate. While preventing the formation of lethal IpaC aggregates, DnaK promoted the incorporation of IpaC into large and dynamic complexes (LDCs) restricted at the bacterial pole through nucleoid occlusion. Unlike stable polymers and aggregates, LDCs show dynamic behavior indicating that nucleoid occlusion also applies to complexes formed through transient interactions. Fluorescence recovery after photobleaching analysis shows DnaK-IpaC exchanges between opposite poles and DnaKJE-mediated incorporation of immature substrates in LDCs. These findings reveal a key role for LDCs as reservoirs of functional DnaK-substrates that can be rapidly mobilized for secretion triggered upon bacterial contact with host cells. PMID- 29795187 TI - Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults. AB - Epidemiological studies have confirmed associations of the vitamin D receptor (VDR) and vitamin D-related gene polymorphisms with adiposity and other metabolic disturbances. Those associations may be sex-specific. We evaluated the cross sectional and longitudinal relationships between metabolic disturbances and haplotypes constructed from single nucleotide polymorphisms of VDR (BsmI:G/A: rs1544410; ApaI:A/C: rs7975232; and TaqI:G/A: rs731236) and MEGALIN (rs3755166:G/A; rs2075252:C/T and rs2228171:C/T) genes, in a sample of African American adults. From 1,024 African Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, 2004-2013, Baltimore, MD), our analyses included 539 participants with complete genetic, baseline covariate and metabolic outcome data (at baseline and follow-up). Mean +/- SD period of follow-up was 4.64 +/- 0.93 y. Multivariable-adjusted Cox proportional hazards and logistic regression models were conducted. Among key findings, in men, incident hypertension was inversely related to MEGALIN1 (GCC), [HR = 0.45, 95% CI: 0.23-0.90, p = 0.024]. Overall, there was a direct, linear dose-response association between VDR2 (AAG: BAt) and MetS at baseline [OR = 1.60, 95% CI: 1.11 2.31, p = 0.012], while among men, VDR3 (GAA: bAT) was inversely related to baseline MetS [OR = 0.40, 95% CI: 0.19-0.81, p = 0.011]. In conclusion, VDR and MEGALIN gene variations can affect prevalent MetS and the incidence rate of hypertension, respectively, among African-American urban adults. PMID- 29795189 TI - Fetal growth and incidence of atopic dermatitis in early childhood: Results of the Ulm SPATZ Health Study. AB - Fetal growth may be a precursory factor in observed association between birthweight and atopic dermatitis (AD), however, recent studies utilizing fetal ultrasound-based data have reported contradictory results. This study aims to clarify previous findings through comprehensive investigation of association between several trimester-specific ultrasound-based anthropometric measures with AD diagnosis by age 3 years. Measurements of 386 newborns in the Ulm SPATZ Health Study were converted into adjusted z-scores categorized as "low" (<=1 SD below mean), "normal," or "high" (>=1 SD above mean). AD cases were defined using parent- or pediatrician-report of physician-diagnosis or clinical diagnosis. Adjusted risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using modified Poisson regression. Compared to normal, both low and high 2nd trimester abdominal circumference [RR 1.51, (95% CI 1.01; 2.24) and 1.83 (1.21; 2.76)], high 2nd trimester head- abdominal circumference ratio [1.69 (1.16; 2.48)], and faltering 2nd to 3rd trimester [1.59 (1.04; 2.43)] head circumference were associated with greater AD risk. High 3rd trimester femur length [0.54 (0.31; 0.94)] was associated with lower risk. Using more inclusive exposure cut points (0.8 SD), lower 1st trimester crown-rump length was also associated with greater AD risk. Our data suggest several different patterns of fetal growth may be differentially associated with AD. PMID- 29795190 TI - Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity. AB - The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5 fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) expression and increased apoptotic rate. Enforced miR-181a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis, including declined Bcl-2/Bax ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase-9 and caspase-3 activation. However, inhibition of miR-181a was associated with reduced p53-mediated mitochondrial apoptosis induced by 5-FU. Moreover, miR-181a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein degradation. We found that miR-181a directly targeted 3'-UTR of BIRC6 mRNA and negatively regulated BIRC6 expression. In vivo study, knockdown of miR-181a with adeno associated virus harboring miR-181a-tough decoy attenuated 5-FU-induced renal cell apoptosis, inflammation and kidney injury. In conclusion, these results demonstrate that miR-181a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes 5-FU-induced apoptosis in mesangial cells. Inhibition of miR-181a ameliorates 5-FU-induced nephrotoxicity, suggesting that miR-181a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy. PMID- 29795191 TI - The rice blast resistance gene Ptr encodes an atypical protein required for broad spectrum disease resistance. AB - Plant resistance genes typically encode proteins with nucleotide binding site leucine rich repeat (NLR) domains. Here we show that Ptr is an atypical resistance gene encoding a protein with four Armadillo repeats. Ptr is required for broad-spectrum blast resistance mediated by the NLR R gene Pi-ta and by the associated R gene Pi-ta2. Ptr is expressed constitutively and encodes two isoforms that are mainly localized in the cytoplasm. A two base pair deletion within the Ptr coding region in the fast neutron-generated mutant line M2354 creates a truncated protein, resulting in susceptibility to M. oryzae. Targeted mutation of Ptr in a resistant cultivar using CRISPR/Cas9 leads to blast susceptibility, further confirming its resistance function. The cloning of Ptr may aid in the development of broad spectrum blast resistant rice. PMID- 29795192 TI - Dopamine D2 -141C Ins/Del and Taq1A polymorphisms, body mass index, and prediction error brain response. AB - The prediction error model is a widely used paradigm that is conceptually based on neuronal dopamine function. However, whether dopamine receptor gene alleles contribute to human neuroimaging prediction error results is uncertain. Recent research implicated the dopamine D2 receptor in behavior response during a prediction error paradigm and we expected that polymorphisms of that receptor would contribute to prediction error brain response. In this study, healthy female participants in the early follicular phase of the menstrual cycle underwent a taste prediction error paradigm during functional magnetic resonance imaging. Participants were also genotyped for dopamine receptor polymorphisms. Our data suggest that the dopamine D2 receptor -141C Ins/Del and Taq1A polymorphisms together with body mass index selectively explain putamen prediction error response. This was true using a region of interest analysis as well as for a whole-brain analysis (FWE corrected). Polymorphisms for dopamine D1 or D4 receptors, dopamine transporter, or COMT did not significantly contribute to prediction error activation. The prediction error model is a computational reward-learning paradigm that is important in psychiatric research and has been associated with dopamine. The results from this study indicate that dopamine D2 receptor polymorphisms together with body mass index are important determinants to include in research that tests prediction error response of the brain. Psychiatric disorders are frequently associated with elevated or reduced body weight. Adding BMI to genetic information in brain-imaging studies that use reward and the prediction error paradigm may be important to increase validity and reliability of results. PMID- 29795196 TI - Identifying children with Special Health Care Needs in Alexandria, Egypt. AB - BACKGROUND: In developing countries, obtaining reliable prevalence rates for children with special health care needs (CSHCN) is challenging. One of the tools used to identify CSHCN is the CSHCN Screener (not available in Arabic). The aim is to test the feasibility of using an Arabic version of CSHCN screener in identifying CSHCN in the Egyptian setup and to estimate their prevalence in Alexandria. METHODS: A community-based survey was conducted among a representative sample of children using a multistage cluster sampling technique. A pre-designed interviewing questionnaire and the Arabic translation of CSHCN screener were used. RESULTS: The prevalence of CSHCN was 12.2% and 91.8% of them had the three domains of health care needs. The most prevalent conditions requiring special health care were sensory and cognitive impairments and impaired mobility. Type of family was the only significant factor associated with special health care needs. CONCLUSION: It is concluded that the screener can easily be used and help in identifying the majority of children that need to be the focus of the National health care services. It is recommended that the school health services add the screener to assist depicting the existing gaps in the health care system. PMID- 29795193 TI - Longitudinal and cross-sectional investigations of long-term potentiation-like cortical plasticity in bipolar disorder type II and healthy individuals. AB - Visual evoked potential (VEP) plasticity is a promising assay for noninvasive examination of long-term potentiation (LTP)-like synaptic processes in the cerebral cortex. We conducted longitudinal and cross-sectional investigations of VEP plasticity in controls and individuals with bipolar disorder (BD) type II. VEP plasticity was assessed at baseline, as described previously (Elvsashagen et al. Biol Psychiatry 2012), and 2.2 years later, at follow-up. The longitudinal sample with VEP data from both time points comprised 29 controls and 16 patients. VEP data were available from 13 additional patients at follow-up (total n = 58). VEPs were evoked by checkerboard reversals in two premodulation blocks before and six blocks after a plasticity-inducing block of prolonged (10 min) visual stimulation. VEP plasticity was computed by subtracting premodulation VEP amplitudes from postmodulation amplitudes. Saliva samples for cortisol analysis were collected immediately after awakening in the morning, 30 min later, and at 12:30 PM, at follow-up. We found reduced VEP plasticity in BD type II, that impaired plasticity was present in the euthymic phases of the illness, and that VEP plasticity correlated negatively with depression severity. There was a positive association between VEP plasticity and saliva cortisol in controls, possibly reflecting an inverted U-shaped relationship between cortisol and synaptic plasticity. VEP plasticity exhibited moderate temporal stability over a period of 2.2 years. The present study provides additional evidence for impaired LTP-like cortical plasticity in BD type II. VEP plasticity is an accessible method, which may help elucidate the pathophysiological and clinical significance of synaptic dysfunction in psychiatric disorders. PMID- 29795197 TI - Prospective plasma proteome changes in preterm infants with different gestational ages. AB - BACKGROUND: In this study, we aimed to analyze time-resolved plasma proteome changes in preterm neonates stratified by their gestational age to detect malfunctioning pathways that derive from the systemic immaturity of the neonate and to highlight those that are differentially regulated during the early development. METHODS: Preterm newborns were enrolled in three subgroups with different gestational ages: before 26 weeks of gestation (group 1), between 27 and 28 weeks of gestation (group 2), and between 29 and 30 (group 3) weeks of gestation. Plasma protein abundances were assessed at two time points (at preterm delivery and at the 36th week of post-menstrual age) by quantitative proteomics. RESULT: The quantitative analysis of plasma proteome in preterm infants revealed a multitude of time-related differences in protein abundances between the studied groups. We report protein changes in several functional domains, including inflammatory domains, immunomodulatory factors, and coagulation regulators as key features, with important gestational age-dependent hemopexin induction. CONCLUSION: The global trend emerging from our data, which can collectively be interpreted as a progression toward recovery from the perinatal perturbations, highlights the profound impact of gestation duration on the ability to bridge the gap in systemic homeostasis after preterm labor. PMID- 29795194 TI - Postnatal DNA demethylation and its role in tissue maturation. AB - Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using. conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl cytosine regulation as an epigenetic mechanism underlying cellular responses to. changing environment. PMID- 29795195 TI - Combining laser capture microdissection and proteomics reveals an active translation machinery controlling invadosome formation. AB - Invadosomes are F-actin-based structures involved in extracellular matrix degradation, cell invasion, and metastasis formation. Analyzing their proteome is crucial to decipher their molecular composition, to understand their mechanisms, and to find specific elements to target them. However, the specific analysis of invadosomes is challenging, because it is difficult to maintain their integrity during isolation. In addition, classical purification methods often suffer from contaminations, which may impair data validation. To ensure the specific identification of invadosome components, we here develop a method that combines laser microdissection and mass spectrometry, enabling the analysis of subcellular structures in their native state based on low amounts of input material. Using this combinatorial method, we show that invadosomes contain specific components of the translational machinery, in addition to known marker proteins. Moreover, functional validation reveals that protein translation activity is an inherent property of invadosomes, which is required to maintain invadosome structure and activity. PMID- 29795198 TI - The association of ambient PM2.5 with school absence and symptoms in schoolchildren: a panel study. AB - BACKGROUND: Children are a susceptible population to exposure of ambient fine particulate air pollution (PM2.5), and the associated symptoms are sensitive prevalent indicators of morbidity. However, few studies to date investigate the association between PM2.5 exposure and school absence and symptoms. METHODS: In a panel study including 20,291 observations in 615 schoolchildren 8-13 years of age, we asked the participants to record their school absence and symptoms on every school day from 17 November to 31 December 2014 in Jinan, China. We used the generalized linear mixed effects models to examine the adverse effects of ambient PM2.5 on school absence and symptoms, adjusting for covariates including meteorological and individual factors. RESULTS: The 3-day moving average of PM2.5 was significantly associated with school absence (1.37; 95% CI: 1.07-1.74) and increases in symptoms of the throat (1.03; 95% CI: 1.00-1.05), nose (1.03; 95% CI: 1.01-1.06), and skin (1.09; 95% CI: 1.06-1.12). High PM2.5 exposure also increased the risks of individual symptoms, especially for cough (1.02; 95% CI: 1.00-1.04), sneezing (1.03; 95% CI: 1.00-1.07), and stuffy nose (1.09; 95% CI: 1.02-1.17). CONCLUSION: High PM2.5 exposure is a risk factor for the health of schoolchildren. Allocation of medical resources for children should take into account the ambient PM2.5 concentrations and be proportioned accordingly. PMID- 29795199 TI - The interrelationship between hepcidin, vitamin D, and anemia in children with acute infectious disease. AB - BACKGROUND: Hepcidin is a master regulator of iron metabolism. Recently, it has been shown that vitamin D suppresses hepcidin expression. Our hypothesis was that hepcidin levels inversely correlate with vitamin D levels in anemic children during acute infection. METHODS: A prospective study was performed on 90 patients (45 females, 45 males, mean age 7.3 +/- 5 years) who were admitted to the pediatric ward. Sixty-two patients had infectious disease (32 with coexisting anemia, 30 without anemia), and 28 patients were hospitalized for noninfectious causes. Blood samples for IL-6, hepcidin, iron status parameters, and 25 hydroxyvitamin D (25-OHD) were obtained within 72 h after admission. RESULTS: Serum concentrations of IL-6 and hepcidin were significantly higher and 25-OHD, iron, and transferrin were significantly lower in anemic children with infectious disease compared with controls. Children with a serum 25-OHD level < 20 ng/ml had significantly increased odds of having anemia than those with a level > 20 ng/ml (OR: 6.1, CI: 1.15-32.76). Correlation analyses found positive associations between hepcidin levels and ferritin (R2 = 0.47, P < 0.001) and negative associations between hepcidin and transferrin (R2 = 0.57, P < 0.001). CONCLUSION: Higher IL-6 and lower 25-OHD levels may lead to higher hepcidin levels and subsequently to hypoferremia and anemia in children with acute infection. PMID- 29795200 TI - Gastrointestinal pathogens in anti-FH antibody positive and negative Hemolytic Uremic Syndrome. AB - BACKGROUND: Prodromal symptoms are frequently reported in the atypical form of Hemolytic uremic syndrome (aHUS) suggesting implication of infectious triggers. Some pathogens may also play a role in the mechanisms of production of autoantibody directed against Factor H (FH), a complement regulator, leading to aHUS. METHODS: The presence of 15 gastrointestinal (GI) pathogens was investigated by using xTAG-based multiplex PCR techniques on stools collected at the acute phase in a cohort of Indian HUS children classified according to the presence or absence of anti-FH autoantibodies. RESULTS: Prevalence of pathogens in patients with anti-FH antibody (62.5%) was twice that in those without (31.5%). Different pathogens were detected, the most frequent being Clostridium difficile, Giardia intestinalis, Salmonella, Shigella, Rotavirus, Norovirus and Entamoeba histolytica. No stool was positive for Shigatoxin. CONCLUSION: This study reveals a higher prevalence of GI pathogens in anti-FH positive than in negative patients. No single pathogen was implicated exclusively in one form of HUS. These pathogens may play a role in the disease initiation by inducing complement activation or an autoimmune response. PMID- 29795201 TI - Characterization and origin of heme precursors in amniotic fluid: lessons from normal and pathological pregnancies. AB - BACKGROUND: Heme is the prosthetic group of numerous proteins involved in vital processes such as oxygen transport, oxidative stress, and energetic mitochondrial metabolism. Free heme also plays a significant role at early stages of development and in cell differentiation processes. The metabolism of heme by the fetal placenta unit is not well-established in humans. METHODS: In a retrospective study, we measured heme precursors in the amniotic fluid (AF) of 51 healthy women, and 10 AF samples from pregnancies with either upper or lower intestinal atresia or ileus were also analyzed. RESULTS: We showed that the porphyrin precursors aminolevulinic acid, porphobilinogen, and protoporphyrin IX are present at the limit of detection in the AF. Total porphyrin levels decreased progressively from week 13 to week 33 (p < 0.01). Interestingly, uroporphyrin, initially detected as traces, increased with maturation, in contrast to coproporphyrin. Uro- and coproporphyrins were type I immature isomers (>90%), suggesting a lack of maturity in the fetal compartment of the heme pathway. Finally, the differential analysis of AF from normal and pathological pregnancies demonstrated the predominant hepatic origin of fetal porphyrins excreted in the AF. CONCLUSION: This study gives the first insight into heme metabolism in the AF during normal and pathological pregnancies. PMID- 29795202 TI - Perspectives from the Society for Pediatric Research: interventions targeting social needs in pediatric clinical care. AB - The social determinants of health (SDoH) are defined by the World Health Organization as the "conditions in which people are born, grow, live, work, and age." Within pediatrics, studies have highlighted links between these underlying social, economic, and environmental conditions, and a range of health outcomes related to both acute and chronic disease. Additionally, within the adult literature, multiple studies have shown significant links between social problems experienced during childhood and "adult diseases" such as diabetes mellitus and hypertension. A variety of potential mechanisms for such links have been explored including differential access to care, exposure to carcinogens and pathogens, health-affecting behaviors, and physiologic responses to allostatic load (i.e., toxic stress). This robust literature supports the importance of the SDoH and the development and evaluation of social needs interventions. These interventions are also driven by evolving economic realities, most importantly, the shift from fee for-service to value-based payment models. This article reviews existing evidence regarding pediatric-focused clinical interventions that address the SDoH, those that target basic needs such as food insecurity, housing insecurity, and diminished access to care. The paper summarizes common challenges encountered in the evaluation of such interventions. Finally, the paper concludes by introducing key opportunities for future inquiry. PMID- 29795203 TI - Backpack weight and back pain reduction: effect of an intervention in adolescents. AB - BACKGROUND: To assess if an educational intervention is effective to reduce backpack weight and back pain in schoolchildren. METHODS: We designed an intervention study in schoolchildren aged between 12 and 16 years aimed to reduce the weight of backpacks and back pain. The intervention was multifaceted, including an educational intervention with practical examples, advising on performing sports, postural habits, leaflets, stickers, and so on. The comparison group did not receive any intervention. RESULTS: A total of 1668 schoolchildren took part in the study. We observed a high prevalence of carrying heavy backpacks, with 66-80% of schoolchildren carrying backpacks surpassing 10% of their body weight. Back pain prevalence was 30%. We observed that the intervention was significant in reducing the backpack weight in first-year schoolchildren but not in second-year. The intervention was also significant in reducing back pain in third-year schoolchildren but only in girls. CONCLUSION: This study shows that an inexpensive intervention directed to reduce the backpack weight and back pain might have a positive effect in schoolchildren. PMID- 29795204 TI - Neonatal sepsis leads to early rise of rare serum bile acid tauro-omega muricholic acid (TOMCA). AB - BACKGROUND: We investigated 'rare' bile acids (BA) as potential markers in septic neonates. METHODS: 'Rare' (C-6 hydroxylated BA) and 'classical' BA were determined in 102 neonates using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Four groups according to maturity (full term, FT vs. preterm, PT) and septic status (early-onset neonatal sepsis, EOS vs. CTR; non-septic controls) were formed: FT-CTR; (n = 47), PT-CTR (n = 22), FT-EOS (n = 20), PT-EOS (n = 13). RESULTS: Firstly, FT-CTR had a significant higher amount of 'rare' BA than PT (FT-CTR: 0.5 umol/L, IQR: 0.3-1.3 vs. PT-CTR: 0.01 umol/L, IQR 0.01-0.2; p < 0.01). The most common 'rare' BA in FT-CTR were tauro gamma- (TGMCA) and tauro-alpha-muricholic acid (TAMCA). Secondly, in EOS, absolute 'rare' BA levels were comparable in both gestational age groups (FT-EOS: 0.6 umol/L, IQR: 0.1-1.6 and PT-EOS: 0.6 umol/L, IQR: 0.2-1.5). Therefore, EOS had significantly higher median 'rare' BA values than non-septic PT neonates (p < 0.01). In PT and term neonates, the relative amount of tauro-omega-muricholic acid (TOMCA) within the 'rare' BA pool was significantly higher in EOS than in controls (FT-CTR vs. "FT-EOS and PT-CTR vs. PT-EOS; p < 0.01). It was hence the predominant 'rare' BA in EOS. CONCLUSION: TOMCA is an independent factor associated with EOS. It has diagnostic potential. PMID- 29795205 TI - Revival of an ancient Greek art: scent detection as diagnostic tool for tuberculosis. PMID- 29795206 TI - Estimating secular changes in longitudinal growth patterns underlying adult height with the QEPS model: the Grow Up Gothenburg cohorts. AB - BACKGROUND: Over the past 150 years, humans have become taller, and puberty has begun earlier. It is unclear if these changes are continuing in Sweden, and how longitudinal growth patterns are involved. We aimed to evaluate the underlying changes in growth patterns from birth to adulthood by QEPS estimates in two Swedish cohorts born in 1974 and 1990. METHODS: Growth characteristics of the longitudinal 1974 and 1990-birth cohorts (n = 4181) were compared using the QEPS model together with adult heights. RESULTS: There was more rapid fetal/infancy growth in girls/boys born in 1990 compared to 1974, as shown by a faster Etimescale and they were heavier at birth. The laterborn were taller also in childhood as shown by a higher Q-function. Girls born in 1990 had earlier and more pronounced growth during puberty than girls born in 1974. Individuals in the 1990 cohort attained greater adult heights than those in the 1974 cohort; 6 mm taller for females and 10 mm for males. CONCLUSION: A positive change in adult height was attributed to more growth during childhood in both sexes and during puberty for girls. The QEPS model proved to be effective detecting small changes of growth patterns, between two longitudinal growth cohorts born only 16 years apart. PMID- 29795207 TI - Predictors of mortality among hospitalized children with severe acute malnutrition: a prospective study from Uganda. AB - BACKGROUND: We determined the predictors of mortality among children admitted with severe acute malnutrition (SAM). METHODS: This was a prospective study nested in a randomized trial among 6-59-month-old children admitted with SAM. Socio-demographic and medical history data were collected using questionnaires and clinical examination, anthropometry and laboratory tests were performed. They were monitored daily until discharge or death during hospitalization while receiving care according to national guidelines. Predictors of death were assessed using Cox regression. RESULTS: Of 400 children, 9.8% (n = 39) died during hospitalization. Predictors of mortality included diarrhoea at admission [hazard ratio [HR] 2.19, 95% confidence interval (CI): 1.06; 4.51], lack of appetite [HR 4.50, 95% CI: 1.76; 11.50], suspected sepsis [HR 2.23, 95% CI: 1.18; 4.24] and skin ulcers [HR 4.23, 95% CI: 1.26; 4.17]. Chest indrawing [HR 5.0, 95% CI: 1.53; 16.3], oxygen saturation below 94% [HR 3.92, 95% CI: 1.42; 10.83] and confirmed HIV infection [HR 3.62, 95% CI: 1.69; 7.77] also predicted higher mortality. CONCLUSION: Infections were major contributors to mortality. This underscores the need for improved prevention and management of these infections among children with severe malnutrition. PMID- 29795208 TI - Pseudomonas aeruginosa-derived exosomes ameliorates allergic reactions via inducing the Treg response in asthma. AB - BACKGROUND: Exosomes are nanovesicles originating from multivesicular bodies that have complex functions and significant therapeutic effects in many diseases. In the present study, we successfully extracted exosomes from Pseudomonas aeruginosa and assessed the effect of those exosomes on the development of the allergic response in two types of classic asthma models. METHODS: Female BALB/c mice were administrated with P. aeruginosa-derived exosomes 1 week before ovalbumin (OVA) or house dust mite (HDM) sensitization. Bronchoalveolar lavage fluid, serums and lung tissues were collected and analyzed for pathophysiology and immune responses. RESULTS: Our results demonstrated that P. aeruginosa-derived exosomes inhibited the development of airway hyper-responsiveness (AHR), peribronchial and perivascular inflammation in lung tissues and the level of serum IgE. Moreover, this protective effect was associated with an increase in the regulatory T cell (Treg) response and a concomitant decreased Th2 response. CONCLUSIONS: In conclusion, these observations demonstrated that P. aeruginosa-derived exosomes could induce protection against allergic sensitization in asthma mice, and our study provided a new insight to prevent allergic diseases. PMID- 29795210 TI - Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats. AB - BACKGROUND: Maternal thyroid deficiency can increase Rho-kinase procontractile influence in arteries of 2-week-old progeny. Here we hypothesized that augmented role of Rho-kinase persists in arteries from adult progeny of hypothyroid rats. METHODS: Dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%) during pregnancy and 2 weeks postpartum; control (CON) females received PTU-free water. At the age of 10-12-weeks, serum T3/T4 levels did not differ between PTU and CON male offspring. Cutaneous (saphenous), mesenteric, and skeletal muscle (sural) arteries were studied by wire myography, qPCR, and Western blotting. RESULTS: Saphenous arteries of PTU and CON groups showed similar responses to alpha1-adrenoceptor agonist methoxamine and were equally suppressed by Rho-kinase inhibitor Y27632. Responses of mesenteric arteries also did not differ between PTU and CON, but the effects of Y27632 were more prominent in the PTU group. Sural arteries of PTU rats compared to CON demonstrated augmented responses to methoxamine, increased RhoA mRNA contents and higher levels of MYPT1 phosphorylation at Thr855. Intergroup differences in contractile responses and phospho-MYPT1-Thr855 were eliminated by Y27632. CONCLUSION: Rho kinase contribution to contractile responses of mesenteric and especially sural arteries is augmented in adult PTU rats. Therefore, maternal thyroid deficiency may have long-term detrimental consequences for vasculature in adult offspring. PMID- 29795209 TI - The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth. AB - BACKGROUND: The impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts. METHODS: To determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 176 term infants in the New Hampshire Birth Cohort Study. Gut colonization patterns were determined with 16S rDNA microbiome profiling. RESULTS: Gut bacterial alpha-diversity differed between premature and term infants at 6 weeks of age, after adjusting for exposures (p = 0.027). Alpha diversity varied between extremely premature (<28 weeks gestation) and very premature infants (>=28 but <32 weeks, p = 0.011), as well as between extremely and moderate-to-late premature infants (>=32 and <37 weeks, p = 0.004). Newborn antibiotic use among premature infants was associated with lower Bifidobacterium and Bacteroides abundance (p = 0.015 and p = 0.041). CONCLUSION: Gestational age at birth and early antibiotic exposure have significant effects on the premature infant gut microbiota. PMID- 29795211 TI - Incidence of neonatal hypertension from a large multicenter study [Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates-AWAKEN]. AB - BACKGROUND: Hypertension occurs in up to 3% of neonates admitted to the Neonatal Intensive Care Unit (NICU), and is a potentially under-recognized condition. The aim of this study was to examine the incidence of documented and undiagnosed hypertension from the 24-center Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) database, and to assess risk factors for hypertension according to gestational age. METHODS: Diagnosed hypertension was documented if an infant had a discharge diagnosis of hypertension and/or discharged on antihypertensive medications. Undiagnosed hypertension was defined when infants did not have a diagnosis of hypertension, but >50% of the lowest mean, diastolic and systolic blood pressure recordings were >95th percentile for gestational age. RESULTS: Of the 2162 neonates enrolled in the study, hypertension was documented in 1.8%. An additional 3.7% were defined as having undiagnosed hypertension. There was a significant correlation with neonatal hypertension and acute kidney injury (AKI). Additional risk factors for neonatal hypertension were hyperbilirubinaemia, Caucasian race, outborn, vaginal delivery, and congenital heart disease. Protective factors were small for gestational age, multiple gestations, and steroids for fetal maturation. CONCLUSIONS: Neonatal hypertension may be an under-recognized condition. AKI and other risk factors predispose infants to hypertension. PMID- 29795214 TI - Heme oxygenase-1 deficiency promotes severity of sepsis in a non-surgical preterm mouse model. AB - BACKGROUND: Sepsis in preterm infants is associated with systemic inflammatory responses. The stress-response protein heme oxygenase-1 (HO-1) has protective anti-inflammatory properties. Recently, we reported a protective role of HO-1 using our non-surgical cecal slurry (CS) model in wild-type (WT) mouse pups. Here, we extend these findings to investigate the association of HO-1 deficiency with sepsis severity. METHODS: Adapting the Wynn model, we induced sepsis in 4 day-old HO-1-deficient (HO-1+/-, Het) pups to determine if HO-1 deficiency affected survival rates at the LD40 (2.0 mg/g) of WT pups. To see if HO-1 induction affected sepsis severity, we gave 30-MUmol heme/kg subcutaneously to 3 day-old mice 24 h prior to sepsis induction. RESULTS: Post-sepsis induction, Het pups had a mortality of 85.0% (n = 20) and increased expression of the pro inflammatory gene in the livers and affected hematologic profiles. Heme treatment 24 h prior to sepsis induction significantly increased liver HO activity, reduced mortality to 24.5% (n = 17), attenuated inflammatory responses, reduced spleen bacterial counts, and significantly increased peripheral neutrophils. CONCLUSIONS: A partial deficiency in HO-1 increased the progression and mortality in sepsis. Furthermore, induction of HO-1 significantly reduced the mortality even in Het pups. Thus, we conclude that HO-1 plays an important role in the protection against preterm sepsis. PMID- 29795215 TI - The big squeeze. PMID- 29795212 TI - Neonatal autonomic function after pregnancy complications and early cardiovascular development. AB - BACKGROUND: Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. METHODS: Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. RESULTS: Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point. CONCLUSIONS: Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk. PMID- 29795213 TI - US adolescents at risk for not meeting physical activity recommendations by season. AB - BACKGROUND: We sought to identify regional and seasonal variation in not meeting physical activity (PA) recommendations of >=60 min a day of moderate-to-vigorous PA (MVPA) and 3 h of vigorous PA per week (VPA) in a longitudinal cohort of United States (US) adolescents. METHODS: Participants in the Growing Up Today Study 2, a prospective study of 10,918 adolescents, self-reported season-specific weekly hours of MVPA and VPA from 2004 through 2011. To assess variation in PA by climate, we grouped the contiguous US into nine climatically consistent geographic regions. We also examined MVPA and VPA by season, sex, ethnicity, weight status, and age group. RESULTS: The majority (85%) of adolescents did not meet the MVPA recommendation, and 91% did not meet the VPA recommendation, for one or more seasons over the four study years. Across all climate regions, adolescents were two times more likely to not meet the MVPA recommendation during the winter compared to summer (odds ratio 2.02, 95% confidence interval: 1.96 2.08). CONCLUSION: Regardless of climate region, gender, ethnicity, or age group, adolescents were more likely not to meet MVPA or VPA recommendations in the winter than the summer. Adolescents may benefit from interventions aimed at increasing PA in the winter. PMID- 29795217 TI - Cells and materials in immunotherapy. PMID- 29795216 TI - Cancer immunotherapy making headway. PMID- 29795218 TI - Tailor-made currents. PMID- 29795219 TI - Rejuvenating zinc batteries. PMID- 29795220 TI - Smart delivery of vaccines. PMID- 29795221 TI - Material aid for vaccines. PMID- 29795222 TI - Dendritic cells in cancer immunotherapy. PMID- 29795223 TI - Zombie materials. PMID- 29795224 TI - Adoptive T cell cancer therapy. PMID- 29795227 TI - Author Correction: Prediction of size-resolved number concentration of cloud condensation nuclei and long-term measurements of their activation characteristics. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29795226 TI - High Redundancy as well as Complementary Prey Choice Characterize Generalist Predator Food Webs in Agroecosystems. AB - Food web structure influences ecosystem functioning and the strength and stability of associated ecosystem services. With their broad diet, generalist predators represent key nodes in the structure of many food webs and they contribute substantially to ecosystem services such as biological pest control. However, until recently it has been difficult to empirically assess food web structure with generalist predators. We utilized DNA-based molecular gut-content analyses to assess the prey use of a set of generalist invertebrate predator species common in temperate agricultural fields. We investigated the degree of specialization of predator-prey food webs at two key stages of the cropping season and analysed the link temperature of different trophic links, to identify non-random predation. We found a low level of specialization in our food webs, and identified warm and cool links which may result from active prey choice or avoidance. We also found a within-season variation in interaction strength between predators and aphid pests which differed among predator species. Our results show a high time-specific functional redundancy of the predator community, but also suggest temporally complementary prey choice due to within season succession of some predator species. PMID- 29795225 TI - Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes. AB - Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5' splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformations of TSL2 and promotes a shift to triloop conformations that display enhanced E7 splicing. Collectively, our study validates TSL2 as a target for small-molecule drug discovery in SMA, identifies a novel mechanism of action for an E7 splicing modifier, and sets a precedent for other splicing-mediated diseases where RNA structure could be similarly targeted. PMID- 29795228 TI - Identification of small molecule compounds targeting the interaction of HIV-1 Vif and human APOBEC3G by virtual screening and biological evaluation. AB - Human APOBEC3G (hA3G) is a restriction factor that inhibits human immunodeficiency 1 virus (HIV-1) replication. The virally encoded protein Vif binds to hA3G and induces its degradation, thereby counteracting the antiviral activity of hA3G. Vif-mediated hA3G degradation clearly represents a potential target for anti-HIV drug development. Herein, we have performed virtual screening to discover small molecule inhibitors that target the binding interface of the Vif/hA3G complex. Subsequent biochemical studies have led to the identification of a small molecule inhibitor, IMB-301 that binds to hA3G, interrupts the hA3G Vif interaction and inhibits Vif-mediated degradation of hA3G. As a result, IMB 301 strongly inhibits HIV-1 replication in a hA3G-dependent manner. Our study further demonstrates the feasibility of inhibiting HIV replication by abrogating the Vif-hA3G interaction with small molecules. PMID- 29795230 TI - Publisher Correction: Emergence of Different Recombinant Porcine Reproductive and Respiratory Syndrome Viruses, China. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29795229 TI - Hematopoietic Stem Cells as a Novel Source of Dental Tissue Cells. AB - While earlier studies have suggested that cells positive for hematopoietic markers can be found in dental tissues, it has yet to be confirmed. To conclusively demonstrate this, we utilized a unique transgenic model in which all hematopoietic cells are green fluorescent protein+ (GFP+). Pulp, periodontal ligament (PDL) and alveolar bone (AvB) cell culture analysis demonstrated numerous GFP+ cells, which were also CD45+ (indicating hematopoietic origin) and co-expressed markers of cellular populations in pulp (dentin matrix protein-1, dentin sialophosphoprotein, alpha smooth muscle actin [ASMA], osteocalcin), in PDL (periostin, ASMA, vimentin, osteocalcin) and in AvB (Runx-2, bone sialoprotein, alkaline phosphatase, osteocalcin). Transplantation of clonal population derived from a single GFP+ hematopoietic stem cell (HSC), into lethally irradiated recipient mice, demonstrated numerous GFP+ cells within dental tissues of recipient mice, which also stained for markers of cell populations in pulp, PDL and AvB (used above), indicating that transplanted HSCs can differentiate into cells in dental tissues. These hematopoietic-derived cells deposited collagen and can differentiate in osteogenic media, indicating that they are functional. Thus, our studies demonstrate, for the first time, that cells in pulp, PDL and AvB can have a hematopoietic origin, thereby opening new avenues of therapy for dental diseases and injuries. PMID- 29795231 TI - Voting Simulation based Agglomerative Hierarchical Method for Network Community Detection. AB - Community detection has been paid much attention in many fields in recent years, and a great deal of community-detection methods have been proposed. But the time consumption of some of them is heavy, limiting them from being applied to large scale networks. On the contrary, there exist some lower-time-complexity methods. But most of them are non-deterministic, meaning that running the same method many times may yield different results from the same network, which reduces their practical utility greatly in real-world applications. To solve these problems, we propose a community-detection method in this paper, which takes both the quality of the results and the efficiency of the detecting procedure into account. Moreover, it is a deterministic method which can extract definite community structures from networks. The proposed method is inspired by the voting behaviours in election activities in the social society, in which we first simulate the voting procedure on the network. Every vertex votes for the nominated candidates following the proposed voting principles, densely connected groups of vertices can quickly reach a consensus on their candidates. At the end of this procedure, candidates and their own voters form a group of clusters. Then, we take the clusters as initial communities, and agglomerate some of them into larger ones with high efficiency to obtain the resulting community structures. We conducted extensive experiments on some artificial networks and real-world networks, the experimental results show that our proposed method can efficiently extract high-quality community structures from networks, and outperform the comparison algorithms significantly. PMID- 29795233 TI - Theory of Large Intrinsic Spin Hall Effect in Iridate Semimetals. AB - We theoretically investigate the mechanism to generate large intrinsic spin Hall effect in iridates or more broadly in 5d transition metal oxides with strong spin orbit coupling. We demonstrate such a possibility by taking the example of orthorhombic perovskite iridate with nonsymmorphic lattice symmetry, SrIrO3, which is a three-dimensional semimetal with nodal line spectrum. It is shown that large intrinsic spin Hall effect arises in this system via the spin-Berry curvature originating from the nearly degenerate electronic spectra surrounding the nodal line. This effect exists even when the nodal line is gently gapped out, due to the persistent nearly degenerate electronic structure. The magnitude of the spin Hall conductivity is shown to be comparable to the best known example such as doped topological insulators and the biggest in any transition metal oxides. To gain further insight, we compute the intrinsic spin Hall conductivity in both bulk and thin film systems. We find that the geometric confinement in thin films leads to significant modifications of the electronic states, leading to even bigger spin Hall conductivity in certain cases. We compare our findings with the recent experimental report on the discovery of large spin Hall effect in SrIrO3 thin films. PMID- 29795232 TI - Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. AB - Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear. Here we report that the transcription factors Dlx1/2 and Otp coordinate the balanced generation of the two functionally related neurons in the hypothalamic arcuate nucleus, GHRH-neurons promoting the growth and AgRP-neurons controlling the feeding and energy expenditure. Dlx1/2-deficient mice show a loss-of-GHRH-neurons and an increase of AgRP-neurons, and consistently develop dwarfism and consume less energy. These results indicate that Dlx1/2 are crucial for specifying the GHRH-neuronal identity and, simultaneously, for suppressing AgRP-neuronal fate. We further show that Otp is required for the generation of AgRP-neurons and that Dlx1/2 repress the expression of Otp by directly binding the Otp gene. Together, our study demonstrates that the identity of GHRH- and AgRP-neurons is synchronously specified and segregated by the Dlx1/2-Otp gene regulatory axis. PMID- 29795234 TI - Comparative inhibitory profile and distribution of bacterial PARPs, using Clostridioides difficile CD160 PARP as a model. AB - Poly-ADP-ribose polymerases (PARPs) are involved in the regulation of important cellular processes, such as DNA repair, aging and apoptosis, among others. They have been considered as promising therapeutic targets, since human cancer cells carrying BRCA1 and BRCA2 mutations are highly sensitive to human PARP-1 inhibitors. Although extensive work has been carried out with the latter enzyme, little is known on bacterial PARPs, of which only one has been demonstrated to be active. To extend this limited knowledge, we demonstrate that the Gram-positive bacterium Clostridioides difficile CD160 PARP is a highly active enzyme with a high production yield. Its phylogenetic analysis also pointed to a singular domain organization in contrast to other clostridiales, which could be due to the long-term divergence of C. difficile CD160. Surprisingly, its PARP becomes the first enzyme to be characterized from this strain, which has a genotype never before described based on its sequenced genome. Finally, the inhibition study carried out after a high-throughput in silico screening and an in vitro testing with hPARP1 and bacterial PARPs identified a different inhibitory profile, a new highly inhibitory compound never before described for hPARP1, and a specificity of bacterial PARPs for a compound that mimics NAD+ (EB-47). PMID- 29795235 TI - Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61alpha in mouse hearts. AB - Cardiac fibrosis is an independent risk factor for heart failure and even the leading cause of death in myocardial infarction patients. However, molecular mechanisms associated with the pathogenesis of cardiac fibrosis following myocardial infarction are not yet fully understood. Nogo-C protein ubiquitously expresses in tissues including in the heart. Our previous study found that Nogo-C regulated cardiomyocyte apoptosis during myocardial infarction. In the present study, we found that Nogo-C was upregulated in fibrotic hearts after myocardial infarction and in Ang II- or TGF-beta1-stimulated cardiac fibroblasts. Overexpression of Nogo-C in cardiac fibroblasts increased expression of pro fibrogenic proteins, while knockdown of Nogo-C inhibited the fibrotic responses of cardiac fibroblasts to Ang II- or TGF-beta1 stimulation. Functionally, Nogo-C deficiency suppressed pro-fibrogenic proteins in post-myocardial infarction hearts and ameliorated post-myocardial infarction cardiac function. Mechanistically, we found that Nogo-C increased intracellular Ca2+ concentration and buffering Ca2+ totally abolished Nogo-C-induced fibrotic responses. Moreover, overexpression of Nogo-C caused increased Sec61alpha, the Ca2+ leakage channel on endoplasmic reticulum membrane. Nogo-C interacted with Sec61alpha on endoplasmic reticulum and stabilized Sec61alpha protein by inhibiting its ubiquitination. Inhibition or knockdown of Sec61alpha blocked Nogo-C-induced increase of cytosolic Ca2+ concentration and inhibited Nogo-C- and TGF-beta1-induced fibrotic responses in cardiac fibroblasts, suggesting that Nogo-C regulates cardiac fibrosis through interacting with Sec61alpha to mediate the Ca2+ leakage from endoplasmic reticulum. Thus, our results reveal a novel mechanism underlying cardiac fibrosis following myocardial infarction, and provide a therapeutic strategy for cardiac remodeling related heart diseases. PMID- 29795236 TI - Metasurface-assisted orbital angular momentum carrying Bessel-Gaussian Laser: proposal and simulation. AB - Bessel-Gaussian beams have distinct properties of suppressed diffraction divergence and self-reconstruction. In this paper, we propose and simulate metasurface-assisted orbital angular momentum (OAM) carrying Bessel-Gaussian laser. The laser can be regarded as a Fabry-Perot cavity formed by one partially transparent output plane mirror and the other metasurface-based reflector mirror. The gain medium of Nd:YVO4 enables the lasing wavelength at 1064 nm with a 808 nm laser serving as the pump. The sub-wavelength structure of metasurface facilitates flexible spatial light manipulation. The compact metasurface-based reflector provides combined phase functions of an axicon and a spherical mirror. By appropriately selecting the size of output mirror and inserting mode-selection element in the laser cavity, different orders of OAM-carrying Bessel-Gaussian lasing modes are achievable. The lasing Bessel-Gaussian0, Bessel-Gaussian01+, Bessel-Gaussian02+ and Bessel-Gaussian03+ modes have high fidelities of ~0.889, ~0.889, ~0.881 and ~0.879, respectively. The metasurface fabrication tolerance and the dependence of threshold power and output lasing power on the length of gain medium, beam radius of pump and transmittance of output mirror are also discussed. The obtained results show successful implementation of metasurface assisted OAM-carrying Bessel-Gaussian laser with favorable performance. The metasurface-assisted OAM-carrying Bessel-Gaussian laser may find wide OAM-enabled communication and non-communication applications. PMID- 29795238 TI - Intake of cocoa products and risk of type-2 diabetes: the multiethnic cohort. AB - BACKGROUND/OBJECTIVES: As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study. SUBJECTS/METHODS: The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 +/- 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: For chocolate candy, both the highest vs. lowest (>=10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; ptrend = 0.01) and the frequency (>=4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; ptrend = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (>=3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; ptrend = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal weight individuals, and to those without comorbidities. CONCLUSIONS: The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet. PMID- 29795239 TI - Fish consumption and risk of stroke, coronary heart disease, and cardiovascular mortality in a Dutch population with low fish intake. AB - BACKGROUND/OBJECTIVES: Fish consumption of at least 1 portion/week is related to lower cardiovascular disease (CVD) risk. It is uncertain whether a less frequent intake is also beneficial and whether the type of fish matters. We investigated associations of very low intakes of total, fatty, and lean fish, compared with no fish intake, with 18-year incidences of stroke, coronary heart disease (CHD), and CVD mortality. METHODS: Data were used from 34,033 participants, aged 20-70 years, of the EPIC-Netherlands cohort. Baseline (1993-1997) fish consumption was estimated using a food frequency questionnaire. We compared any fish consumption, <1 portion/week (<100 g) and >=1 portion/week to non-fish consumption. RESULTS: During 18 follow-up years, 753 stroke events, 2134 CHD events, and 540 CVD deaths occurred. Among the fish consumers (~92%) median intakes of total, lean, and fatty fish were 57.9, 32.9, and 10.7 g/week, respectively. Any fish consumption compared with non-consumption was not associated with incidences of stroke, CHD, MI, and CVD mortality. Furthermore, consumption of <1 portion/week of total, fatty, or lean fish was not associated with any CVD outcome, as compared with non consumption. Consumption of >=1 portion/week of lean fish (HR: 0.70, 95% CI: 0.57 0.86) and of fatty fish (HR: 0.63, 95% CI: 0.39-1.02) were associated with lower incidence of ischaemic stroke. CONCLUSIONS: Baseline fish consumption of <1 portion/week, regardless of the type of fish, was unrelated to incidences of stroke, CHD, and CVD mortality in this Dutch cohort. Consumption of >=1 portion/week of fatty or of lean fish reduced the incidence of ischaemic stroke. PMID- 29795237 TI - Ethnic, geographic and dietary differences in arsenic exposure in the multi ethnic study of atherosclerosis (MESA). AB - Differences in residential location as well as race/ethnicity and dietary habits may result in differences in inorganic arsenic (iAs) exposure. We investigated the association of exposure to iAs with race/ethnicity, geography, and dietary intake in a random sample of 310 White, Black, Hispanic, and Chinese adults in the Multi-Ethnic Study of Atherosclerosis from 6 US cities with inorganic and methylated arsenic (SigmaAs) measured in urine. Dietary intake was assessed by food-frequency questionnaire. Chinese and Hispanic race/ethnicity was associated with 82% (95% CI: 46%, 126%) and 37% (95% CI: 10%, 70%) higher urine arsenic concentrations, respectively, compared to White participants. No differences were observed for Black participants compared to Whites. Urine arsenic concentrations were higher for participants in Los Angeles, Chicago, and New York compared to other sites. Participants that ate rice >=2 times/week had 31% higher urine arsenic compared to those that rarely/never consumed rice. Participants that drank wine >=2 times/week had 23% higher urine arsenic compared to rare/never wine drinkers. Intake of poultry or non-rice grains was not associated with urinary arsenic concentrations. At the low-moderate levels typical of the US population, exposure to iAs differed by race/ethnicity, geographic location, and frequency of rice and wine intake. PMID- 29795240 TI - The pattern of the M-protein in smoldering myeloma over the time: an evolving risk factor. PMID- 29795242 TI - Interventions to promote cardiometabolic health and slow cardiovascular ageing. AB - Cardiovascular ageing and the atherosclerotic process begin very early in life, most likely in utero. They progress over decades of exposure to suboptimal or abnormal metabolic and hormonal risk factors, eventually culminating in very common, costly, and mostly preventable target-organ pathologies, including coronary heart disease, stroke, heart failure, aortic aneurysm, peripheral artery disease, and vascular dementia. In this Review, we discuss findings from preclinical and clinical studies showing that calorie restriction (CR), intermittent fasting, and adjusted diurnal rhythm of feeding, with adequate intake of specific macronutrients and micronutrients, are powerful interventions not only for the prevention of cardiovascular disease but also for slowing the accumulation of molecular damage leading to cardiometabolic dysfunction. Furthermore, we discuss the mechanisms through which a number of other nondietary interventions, such as regular physical activity, mindfulness-based stress reduction exercises, and some CR-mimetic drugs that target pro-ageing pathways, can potentiate the beneficial effects of a healthy diet in promoting cardiometabolic health. PMID- 29795241 TI - Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) cases showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extra-terminal protein (BETis), and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN, in accordance with precision medicine. PMID- 29795243 TI - FGF21 ACEs hypertension. PMID- 29795246 TI - AhR controls tolerance to cell debris. PMID- 29795247 TI - Relationship between agro-environmental variables and breeding Hylids in rice paddies. AB - When natural wetlands are destroyed, many anuran species are forced to breed in alternative habitats such as rice paddies. We conducted field surveys for the endangered Dryophytes suweonensis and the numerous D. japonicus, from the beginning of the breeding season until two weeks after its peak. We recorded the presence, number of individuals and calling indices for each species. We hypothesized that D. japonicus would start breeding earlier than D. suweonensis, which would have originally been breeding solely in floodplains. The results of our analyses demonstrate that the rice cultivation phase was the most important factor in predicting the calling activities of both species. Furthermore, peak calling activities of both species matched the optimal hydroperiod in rice paddies. In addition, D. japonicus breeding behaviour was influenced by environmental variables such as temperature, whereas D. suweonensis seemed to require the planting of rice seedlings to initiate breeding. Therefore, as both Dryophytes species' breeding activities are influenced by agro-environmental variables, this study highlights the importance of also preserving anthropogenically modified landscapes for the conservation of species. PMID- 29795244 TI - Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk. AB - Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents. PMID- 29795249 TI - Signal of GV1001 efficacy. PMID- 29795245 TI - Burst activation of dopamine neurons produces prolonged post-burst availability of actively released dopamine. AB - Both phasic and tonic modes of neurotransmission are implicated in critical functions assigned to dopamine. In learning, for example, sub-second phasic responses of ventral tegmental area (VTA) dopamine neurons to salient events serve as teaching signals, but learning is also interrupted by dopamine antagonists administered minutes after training. Our findings bridge the multiple timescales of dopamine neurotransmission by demonstrating that burst stimulation of VTA dopamine neurons produces a prolonged post-burst increase (>20 min) of extracellular dopamine in nucleus accumbens and prefrontal cortex. This elevation is not due to spillover from the stimulation surge but depends on impulse flow mediated dopamine release. We identified Rho-mediated internalization of dopamine transporter as a mechanism responsible for prolonged availability of actively released dopamine. Thus, a critical consequence of burst activity of dopamine neurons may be post-burst sustained elevation of extracellular dopamine in terminal regions via an intracellular mechanism that promotes dopamine transporter internalization. These results demonstrate that phasic and tonic dopamine neurotransmission can be a continuum and may explain why both modes of signaling are critical for motivational and cognitive functions associated with dopamine. PMID- 29795250 TI - Yes or no to local therapy for oligometastatic prostate cancer? PMID- 29795248 TI - Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2018. AB - Immunoglobulin light chain amyloidosis (AL) should be considered in any patient that presents to a cancer care provider with nephrotic range proteinuria, heart failure with preserved ejection fraction, non-diabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Algorithms will be provided on how to evaluate patients with suspected AL amyloid as well as how to manage patients referred from other medical specialties with biopsy-proven amyloid. An organized stepwise approach to the treatment of patients with light chain amyloidosis, including established and investigational therapies, will be reviewed. PMID- 29795251 TI - Large potential reduction in economic damages under UN mitigation targets. AB - International climate change agreements typically specify global warming thresholds as policy targets 1 , but the relative economic benefits of achieving these temperature targets remain poorly understood2,3. Uncertainties include the spatial pattern of temperature change, how global and regional economic output will respond to these changes in temperature, and the willingness of societies to trade present for future consumption. Here we combine historical evidence 4 with national-level climate 5 and socioeconomic 6 projections to quantify the economic damages associated with the United Nations (UN) targets of 1.5 degrees C and 2 degrees C global warming, and those associated with current UN national-level mitigation commitments (which together approach 3 degrees C warming 7 ). We find that by the end of this century, there is a more than 75% chance that limiting warming to 1.5 degrees C would reduce economic damages relative to 2 degrees C, and a more than 60% chance that the accumulated global benefits will exceed US$20 trillion under a 3% discount rate (2010 US dollars). We also estimate that 71% of countries-representing 90% of the global population-have a more than 75% chance of experiencing reduced economic damages at 1.5 degrees C, with poorer countries benefiting most. Our results could understate the benefits of limiting warming to 1.5 degrees C if unprecedented extreme outcomes, such as large-scale sea level rise 8 , occur for warming of 2 degrees C but not for warming of 1.5 degrees C. Inclusion of other unquantified sources of uncertainty, such as uncertainty in secular growth rates beyond that contained in existing socioeconomic scenarios, could also result in less precise impact estimates. We find considerably greater reductions in global economic output beyond 2 degrees C. Relative to a world that did not warm beyond 2000-2010 levels, we project 15%-25% reductions in per capita output by 2100 for the 2.5-3 degrees C of global warming implied by current national commitments 7 , and reductions of more than 30% for 4 degrees C warming. Our results therefore suggest that achieving the 1.5 degrees C target is likely to reduce aggregate damages and lessen global inequality, and that failing to meet the 2 degrees C target is likely to increase economic damages substantially. PMID- 29795253 TI - Pulsar emission amplified and resolved by plasma lensing in an eclipsing binary. AB - Radio pulsars scintillate because their emission travels through the ionized interstellar medium along multiple paths, which interfere with each other. It has long been realized that, independent of their nature, the regions responsible for the scintillation could be used as 'interstellar lenses' to localize pulsar emission regions1,2. Most such lenses, however, resolve emission components only marginally, limiting results to statistical inferences and detections of small positional shifts3-5. As lenses situated close to their source offer better resolution, it should be easier to resolve emission regions of pulsars located in high-density environments such as supernova remnants 6 or binaries in which the pulsar's companion has an ionized outflow. Here we report observations of extreme plasma lensing in the 'black widow' pulsar, B1957+20, near the phase in its 9.2 hour orbit at which its emission is eclipsed by its companion's outflow7-9. During the lensing events, the observed radio flux is enhanced by factors of up to 70-80 at specific frequencies. The strongest events clearly resolve the emission regions: they affect the narrow main pulse and parts of the wider interpulse differently. We show that the events arise naturally from density fluctuations in the outer regions of the outflow, and we infer a resolution of our lenses that is comparable to the pulsar's radius, about 10 kilometres. Furthermore, the distinct frequency structures imparted by the lensing are reminiscent of what is observed for the repeating fast radio burst FRB 121102, providing observational support for the idea that this source is observed through, and thus at times strongly magnified by, plasma lenses 10 . PMID- 29795252 TI - Rapid emergence of subaerial landmasses and onset of a modern hydrologic cycle 2.5 billion years ago. AB - The history of the growth of continental crust is uncertain, and several different models that involve a gradual, decelerating, or stepwise process have been proposed1-4. Even more uncertain is the timing and the secular trend of the emergence of most landmasses above the sea (subaerial landmasses), with estimates ranging from about one billion to three billion years ago5-7. The area of emerged crust influences global climate feedbacks and the supply of nutrients to the oceans 8 , and therefore connects Earth's crustal evolution to surface environmental conditions9-11. Here we use the triple-oxygen-isotope composition of shales from all continents, spanning 3.7 billion years, to provide constraints on the emergence of continents over time. Our measurements show a stepwise total decrease of 0.08 per mille in the average triple-oxygen-isotope value of shales across the Archaean-Proterozoic boundary. We suggest that our data are best explained by a shift in the nature of water-rock interactions, from near-coastal in the Archaean era to predominantly continental in the Proterozoic, accompanied by a decrease in average surface temperatures. We propose that this shift may have coincided with the onset of a modern hydrological cycle owing to the rapid emergence of continental crust with near-modern average elevation and aerial extent roughly 2.5 billion years ago. PMID- 29795254 TI - Inference of ecological and social drivers of human brain-size evolution. AB - The human brain is unusually large. It has tripled in size from Australopithecines to modern humans 1 and has become almost six times larger than expected for a placental mammal of human size 2 . Brains incur high metabolic costs 3 and accordingly a long-standing question is why the large human brain has evolved 4 . The leading hypotheses propose benefits of improved cognition for overcoming ecological5-7, social8-10 or cultural11-14 challenges. However, these hypotheses are typically assessed using correlative analyses, and establishing causes for brain-size evolution remains difficult15,16. Here we introduce a metabolic approach that enables causal assessment of social hypotheses for brain size evolution. Our approach yields quantitative predictions for brain and body size from formalized social hypotheses given empirical estimates of the metabolic costs of the brain. Our model predicts the evolution of adult Homo sapiens-sized brains and bodies when individuals face a combination of 60% ecological, 30% cooperative and 10% between-group competitive challenges, and suggests that between-individual competition has been unimportant for driving human brain-size evolution. Moreover, our model indicates that brain expansion in Homo was driven by ecological rather than social challenges, and was perhaps strongly promoted by culture. Our metabolic approach thus enables causal assessments that refine, refute and unify hypotheses of brain-size evolution. PMID- 29795255 TI - Fundamental limits to graphene plasmonics. AB - Plasmon polaritons are hybrid excitations of light and mobile electrons that can confine the energy of long-wavelength radiation at the nanoscale. Plasmon polaritons may enable many enigmatic quantum effects, including lasing 1 , topological protection2,3 and dipole-forbidden absorption 4 . A necessary condition for realizing such phenomena is a long plasmonic lifetime, which is notoriously difficult to achieve for highly confined modes 5 . Plasmon polaritons in graphene-hybrids of Dirac quasiparticles and infrared photons-provide a platform for exploring light-matter interaction at the nanoscale6,7. However, plasmonic dissipation in graphene is substantial 8 and its fundamental limits remain undetermined. Here we use nanometre-scale infrared imaging to investigate propagating plasmon polaritons in high-mobility encapsulated graphene at cryogenic temperatures. In this regime, the propagation of plasmon polaritons is primarily restricted by the dielectric losses of the encapsulated layers, with a minor contribution from electron-phonon interactions. At liquid-nitrogen temperatures, the intrinsic plasmonic propagation length can exceed 10 micrometres, or 50 plasmonic wavelengths, thus setting a record for highly confined and tunable polariton modes. Our nanoscale imaging results reveal the physics of plasmonic dissipation and will be instrumental in mitigating such losses in heterostructure engineering applications. PMID- 29795256 TI - Addressing the minimum fleet problem in on-demand urban mobility. AB - Information and communication technologies have opened the way to new solutions for urban mobility that provide better ways to match individuals with on-demand vehicles. However, a fundamental unsolved problem is how best to size and operate a fleet of vehicles, given a certain demand for personal mobility. Previous studies1-5 either do not provide a scalable solution or require changes in human attitudes towards mobility. Here we provide a network-based solution to the following 'minimum fleet problem', given a collection of trips (specified by origin, destination and start time), of how to determine the minimum number of vehicles needed to serve all the trips without incurring any delay to the passengers. By introducing the notion of a 'vehicle-sharing network', we present an optimal computationally efficient solution to the problem, as well as a nearly optimal solution amenable to real-time implementation. We test both solutions on a dataset of 150 million taxi trips taken in the city of New York over one year 6 . The real-time implementation of the method with near-optimal service levels allows a 30 per cent reduction in fleet size compared to current taxi operation. Although constraints on driver availability and the existence of abnormal trip demands may lead to a relatively larger optimal value for the fleet size than that predicted here, the fleet size remains robust for a wide range of variations in historical trip demand. These predicted reductions in fleet size follow directly from a reorganization of taxi dispatching that could be implemented with a simple urban app; they do not assume ride sharing7-9, nor require changes to regulations, business models, or human attitudes towards mobility to become effective. Our results could become even more relevant in the years ahead as fleets of networked, self-driving cars become commonplace10-14. PMID- 29795257 TI - How gut microbes are joining the fight against cancer. PMID- 29795260 TI - Telescope pact, volcano explosion and migraine drug. PMID- 29795259 TI - Hong Kong builds a science-based future. PMID- 29795262 TI - Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor. AB - Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role of the multi functional enzyme Transglutaminase 2 (TG2) in cardiac fibrosis and assess its potential as a therapeutic target. Here we describe the use a highly selective TG2 small-molecule inhibitor to test the efficacy of TG2 inhibition as an anti fibrotic therapy for heart failure employing two different in vivo models of cardiac fibrosis: Progressively induced interstitial cardiac fibrosis by pressure overload using angiotensin II infusion: Acutely induced focal cardiac fibrosis through myocardial infarction by ligation of the left anterior descending coronary artery (AMI model). In the AMI model, in vivo MRI showed that the TG2 inhibitor 1-155 significantly reduced infarct size by over 50% and reduced post infarct remodelling at 20 days post insult. In both models, Sirius red staining for collagen deposition and levels of the TG2-mediated protein crosslink epsilon(gamma-glutamyl)lysine were significantly reduced. No cardiac rupture or obvious signs of toxicity were observed. To provide a molecular mechanism for TG2 involvement in cardiac fibrosis, we show that both TGFbeta1-induced transition of cardiofibroblasts into myofibroblast-like cells and TGFbeta1-induced EndMT, together with matrix deposition, can be attenuated by the TG2 selective inhibitor 1-155, suggesting a new role for TG2 in regulating TGFbeta1 signalling in addition to its role in latent TGFbeta1 activation. In conclusion, TG2 has a role in cardiac fibrosis through activation of myofibroblasts and matrix deposition. TG2 inhibition using a selective small-molecule inhibitor can attenuate cardiac fibrosis. PMID- 29795263 TI - Author Correction: Atomic-resolution three-dimensional hydration structures on a heterogeneously charged surface. AB - The original version of the Supplementary Information associated with this Article contained an error in Supplementary Figure 9e,f in which the y-axes were incorrectly labelled from '-40' to '40', rather than the correct '-400' to '400'. The HTML has been updated to include a corrected version of the Supplementary Information. PMID- 29795264 TI - Ultrathin, flexible and multimodal tactile sensors based on organic field-effect transistors. AB - In this study, a novel approach to the fabrication of a multimodal temperature and force sensor on ultrathin, conformable and flexible substrates is presented. This process involves coupling a charge-modulated organic field-effect transistor (OCMFET) with a pyro/piezoelectric element, namely a commercial film of poly vinylene difluoride (PVDF). The proposed device is able to respond to both pressure stimuli and temperature variations, demonstrating the feasibility of the approach for the development of low-cost, highly sensitive and conformable multimodal sensors. The overall thickness of the device is 1.2 MUm, being thus able to conform to any surface (including the human body), while keeping its electrical performance. Furthermore, it is possible to discriminate between simultaneously applied temperature and pressure stimuli by coupling sensing surfaces made of poled and unpoled spin-coated PVDF-trifluoroethylene (PVDF-TrFE, a PVDF copolymer) with OCMFETs. This demonstrates the possibility of creating multimodal sensors that can be employed for applications in several fields, ranging from robotics to wearable electronics. PMID- 29795265 TI - Is GRK2 a new target for cardiovascular disease? PMID- 29795261 TI - Transcriptomic response of breast cancer cells to anacardic acid. AB - Anacardic acid (AnAc), a potential dietary agent for preventing and treating breast cancer, inhibited the proliferation of estrogen receptor alpha (ERalpha) positive MCF-7 and MDA-MB-231 triple negative breast cancer cells. To characterize potential regulators of AnAc action, MCF-7 and MDA-MB-231 cells were treated for 6 h with purified AnAc 24:1n5 congener followed by next generation transcriptomic sequencing (RNA-seq) and network analysis. We reported that AnAc differentially regulated miRNA transcriptomes in each cell line and now identify AnAc-regulated changes in mRNA and lncRNA transcript expression. In MCF-7 cells, 80 AnAc-responsive genes were identified, including lncRNA MIR22HG. More AnAc responsive genes (886) were identified in MDA-MB-231 cells. Only six genes were commonly altered by AnAc in both cell lines: SCD, INSIG1, and TGM2 were decreased and PDK4, GPR176, and ZBT20 were increased. Modeling of AnAc-induced gene changes suggests that AnAc inhibits monounsaturated fatty acid biosynthesis in both cell lines and increases endoplasmic reticulum stress in MDA-MB-231 cells. Since modeling of downregulated genes implicated NFkappaB in MCF-7, we confirmed that AnAc inhibited TNFalpha-induced NFkappaB reporter activity in MCF-7 cells. These data identify new targets and pathways that may account for AnAc's anti proliferative and pro-apoptotic activity. PMID- 29795266 TI - Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin Polyvinylpyrrolidone-Chitosan Systems. AB - By the example of a model process of tryptophan photooxidation in the aqueous medium in the presence of a three-component photosensitizing complex (porphyrin photosensitizer-polyvinylpyrrolidone- chitosan, PPS-PVP-CT) in the temperature range of 20-40 degrees S, we have demonstrated a possibility of modification of such a process by selecting different molar ratios of the components in the reaction mixture. The actual objective of this selection is the formation of a certain PPS-PVP-CT composition in which PVP macromolecules would coordinate with PPS molecules and at the same time practically block the complex binding of PPS molecules with chitosan macromolecules. Such blocking allows utilization of the bactericidal properties of chitosan to a greater extent, since chitosan is known to depress the PPS photosensitizing activity in PPS-PVP-CT complexes when using those in photodynamic therapy (PDT). The optimal composition of photosensitizing complexes appears to be dependent on the temperature at which the PDT sessions are performed. We have analyzed the correlations of the effective rate constants of tryptophan photooxidation with the photophysical characteristics of the formed complexes. PMID- 29795267 TI - Ancient acquisition of "alginate utilization loci" by human gut microbiota. AB - In bacteria from the phylum Bacteroidetes, the genes coding for enzymes involved in polysaccharide degradation are often colocalized and coregulated in so-called "polysaccharide utilization loci" (PULs). PULs dedicated to the degradation of marine polysaccharides (e.g. laminaran, ulvan, alginate and porphyran) have been characterized in marine bacteria. Interestingly, the gut microbiome of Japanese individuals acquired, by lateral transfer from marine bacteria, the genes involved in the breakdown of porphyran, the cell wall polysaccharide of the red seaweed used in maki. Sequence similarity analyses predict that the human gut microbiome also encodes enzymes for the degradation of alginate, the main cell wall polysaccharide of brown algae. We undertook the functional characterization of diverse polysaccharide lyases from family PL17, frequently found in marine bacteria as well as those of human gut bacteria. We demonstrate here that this family is polyspecific. Our phylogenetic analysis of family PL17 reveals that all alginate lyases, which have all the same specificity and mode of action, cluster together in a very distinct subfamily. The alginate lyases found in human gut bacteria group together in a single clade which is rooted deeply in the PL17 tree. These enzymes were found in PULs containing PL6 enzymes, which also clustered together in the phylogenetic tree of PL6. Together, biochemical and bioinformatics analyses suggest that acquisition of this system appears ancient and, because only traces of two successful transfers were detected upon inspection of PL6 and PL17 families, the pace of acquisition of marine polysaccharide degradation system is probably very slow. PMID- 29795270 TI - Next-generation sequencing for measuring minimal residual disease in AML. PMID- 29795271 TI - New evidence for treatment of ALAL. PMID- 29795269 TI - Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility. AB - Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with cyclophosphamide or cisplatin. Cyclophosphamide caused almost complete destruction of the primordial follicle pool in adult wild-type (WT) mice, and a significant destructive effect was also observed for cisplatin. In striking contrast, Puma-/- mice retained 100% of their primordial follicles following either genotoxic treatment. Furthermore, elimination of PUMA alone completely preserved fertility in cyclophosphamide-treated mice, indicating that oocytes rescued from DNA damage-induced death can repair themselves sufficiently to support reproductive function and offspring health. Primordial follicles were also protected in TAp63-/- mice following cisplatin treatment, but not cyclophosphamide, suggesting mechanistic differences in the induction of apoptosis and depletion of the ovarian reserve in response to these different chemotherapies. These studies identify PUMA as a crucial effector of apoptosis responsible for depletion of primordial follicles following exposure to cyclophosphamide or cisplatin, and this indicates that inhibition of PUMA may be an effective ovarian-protective strategy during cancer treatment in women. PMID- 29795272 TI - Extracellular vesicles in cancer - implications for future improvements in cancer care. AB - The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics. PMID- 29795273 TI - Improving the Explosive Performance of Aluminum Nanoparticles with Aluminum Iodate Hexahydrate (AIH). AB - A new synthesis approach for aluminum particles enables an aluminum core to be passivated by an oxidizing salt: aluminum iodate hexahydrate (AIH). Transmission electron microscopy (TEM) images show that AIH replaces the Al2O3 passivation layer on Al particles that limits Al oxidation. The new core-shell particle reactivity was characterized using laser-induced air shock from energetic materials (LASEM) and results for two different Al-AIH core-shell samples that vary in the AIH concentration demonstrate their potential use for explosive enhancement on both fast (detonation velocity) and slow (blast effects) timescales. Estimates of the detonation velocity for TNT-AIH composites suggest an enhancement of up to 30% may be achievable over pure TNT detonation velocities. Replacement of Al2O3 with AIH allows Al to react on similar timescales as detonation waves. The AIH mixtures tested here have relatively low concentrations of AIH (15 wt. % and 6 wt. %) compared to previously reported samples (57.8 wt. %) and still increase TNT performance by up to 30%. Further optimization of AIH synthesis could result in additional increases in explosive performance. PMID- 29795268 TI - Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors. AB - Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice. We find that loss of Trpa1, a pungency/irritancy receptor, diminishes TMT/2MT and snake skin-evoked innate fear/defensive responses. Accordingly, Trpa1 -/- mice fail to effectively activate known fear/stress brain centers upon 2MT exposure, despite their apparent ability to smell and learn to fear 2MT. Moreover, Trpa1 acts as a chemosensor for 2MT/TMT and Trpa1-expressing trigeminal ganglion neurons contribute critically to 2MT-evoked freezing. Our results indicate that Trpa1 mediated nociception plays a crucial role in predator odor-evoked innate fear/defensive behaviors. The work establishes the first forward genetics screen to uncover the molecular mechanism of innate fear, a basic emotion and evolutionarily conserved survival mechanism. PMID- 29795274 TI - Effect of physical activity on pulse wave velocity in elderly subjects with normal glucose, prediabetes or Type 2 Diabetes. AB - Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not. The 2 h glucose, heart rate and alcohol consumption in T2D subjects had independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were significantly associated to (cf)PWV. Interestingly, lipids did not have an additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had 0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of T2D, elevated heart rate and alcohol consumption in males were associated with increased aortic stiffening in elderly subjects. PMID- 29795275 TI - Phenotype and genotype predictors of BMI variability among European adults. AB - BACKGROUND/OBJECTIVE: Obesity is a complex and multifactorial disease resulting from the interactions among genetics, metabolic, behavioral, sociocultural and environmental factors. In this sense, the aim of the present study was to identify phenotype and genotype variables that could be relevant determinants of body mass index (BMI) variability. SUBJECTS/METHODS: In the present study, a total of 1050 subjects (798 females; 76%) were included. Least angle regression (LARS) analysis was used as regression model selection technique, where the dependent variable was BMI and the independent variables were age, sex, energy intake, physical activity level, and 16 polymorphisms previously related to obesity and lipid metabolism. RESULTS: The LARS analysis obtained the following formula for BMI explanation: (64.7 + 0.10 * age [years] + 0.42 * gender [0, men; 1, women] + -40.6 * physical activity [physical activity level] + 0.004 * energy intake [kcal] + 0.74 * rs9939609 [0 or 1-2 risk alleles] + -0.72 * rs1800206 [0 or 1-2 risk alleles] + -0.86 * rs1801282 [0 or 1-2 risk alleles] + 0.87 * rs429358 [0 or 1-2 risk alleles]. The multivariable regression model accounted for 21% of the phenotypic variance in BMI. The regression model was internally validated by the bootstrap method (r2 original data set = 0.208, mean r2 bootstrap data sets = 0.210). CONCLUSION: In conclusion, age, physical activity, energy intake and polymorphisms in FTO, APOE, PPARG and PPARA genes are significant predictors of the BMI trait. PMID- 29795278 TI - Investigation on the interface between Li10GeP2S12 electrolyte and carbon conductive agents in all-solid-state lithium battery. AB - All-solid-state batteries are considered as one of the attractive alternatives to conventional lithium-ion batteries, due to their intrinsic safe properties benefiting from the use of non-flammable solid electrolytes in ASSBs. However, one of the issues in employing the solid-state electrolyte is the sluggish ion transport kinetics arising from the chemical and physical instability of the interfaces among solid components including electrode material, electrolyte and additive agents. In this work, we investigate the stability of the interface between carbon conductive agents and Li10GeP2S12 in a composite cathode and its effect on the electrochemical performance of ASSBs. It is found that the inclusion of various carbon conductive agents in composite cathode leads to inferior kinetic performance of the cathode despite expectedly enhanced electrical conductivity of the composite. We observe that the poor kinetic performance is attributed to a large interfacial impedance which is gradually developed upon the inclusions of the various carbon conductive agents regardless of their physical differences. The analysis through X-ray Photoelectron Spectroscopy suggests that the carbon additives in the composite cathode stimulate the electrochemical decomposition of LGPS electrolyte degrading its surface during cycling, indicating the large interfacial resistance stems from the undesirable decomposition of the electrolyte at the interface. PMID- 29795276 TI - Horizontal operon transfer, plasmids, and the evolution of photosynthesis in Rhodobacteraceae. AB - The capacity for anoxygenic photosynthesis is scattered throughout the phylogeny of the Proteobacteria. Their photosynthesis genes are typically located in a so called photosynthesis gene cluster (PGC). It is unclear (i) whether phototrophy is an ancestral trait that was frequently lost or (ii) whether it was acquired later by horizontal gene transfer. We investigated the evolution of phototrophy in 105 genome-sequenced Rhodobacteraceae and provide the first unequivocal evidence for the horizontal transfer of the PGC. The 33 concatenated core genes of the PGC formed a robust phylogenetic tree and the comparison with single-gene trees demonstrated the dominance of joint evolution. The PGC tree is, however, largely incongruent with the species tree and at least seven transfers of the PGC are required to reconcile both phylogenies. The origin of a derived branch containing the PGC of the model organism Rhodobacter capsulatus correlates with a diagnostic gene replacement of pufC by pufX. The PGC is located on plasmids in six of the analyzed genomes and its DnaA-like replication module was discovered at a conserved central position of the PGC. A scenario of plasmid-borne horizontal transfer of the PGC and its reintegration into the chromosome could explain the current distribution of phototrophy in Rhodobacteraceae. PMID- 29795277 TI - Circuit variability interacts with excitatory-inhibitory diversity of interneurons to regulate network encoding capacity. AB - Local interneurons (LNs) in the Drosophila olfactory system exhibit neuronal diversity and variability, yet it is still unknown how these features impact information encoding capacity and reliability in a complex LN network. We employed two strategies to construct a diverse excitatory-inhibitory neural network beginning with a ring network structure and then introduced distinct types of inhibitory interneurons and circuit variability to the simulated network. The continuity of activity within the node ensemble (oscillation pattern) was used as a readout to describe the temporal dynamics of network activity. We found that inhibitory interneurons enhance the encoding capacity by protecting the network from extremely short activation periods when the network wiring complexity is very high. In addition, distinct types of interneurons have differential effects on encoding capacity and reliability. Circuit variability may enhance the encoding reliability, with or without compromising encoding capacity. Therefore, we have described how circuit variability of interneurons may interact with excitatory-inhibitory diversity to enhance the encoding capacity and distinguishability of neural networks. In this work, we evaluate the effects of different types and degrees of connection diversity on a ring model, which may simulate interneuron networks in the Drosophila olfactory system or other biological systems. PMID- 29795279 TI - Dysregulation of the MiR-449b target TGFBI alters the TGFbeta pathway to induce cisplatin resistance in nasopharyngeal carcinoma. AB - Despite the improvement in locoregional control of nasopharyngeal carcinoma (NPC), distant metastasis (DM), and chemoresistance persist as major causes of mortality. This study identified a novel role for miR-449b, an overexpressed gene in a validated four-miRNA signature for NPC DM, leading to chemoresistance via the direct targeting of transforming growth factor beta-induced (TGFBI). In vitro shRNA-mediated downregulation of TGFBI induced phosphorylation of PTEN and AKT, increasing cisplatin resistance. Conversely, the overexpression of TGFBI sensitized the NPC cells to cisplatin. In NPC patients treated with concurrent chemoradiotherapy (CRT), the overall survival (OS) was significantly inversely correlated with miR-449b, and directly correlated with both TGFBI mRNA and protein expression, as assessed by RNA sequencing and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation demonstrated that TGFBI competes with pro TGFbeta1 for integrin receptor binding. Decreased TGFBI led to increased pro TGFbeta1 activation and TGFbeta1 canonical/noncanonical pathway-induced cisplatin resistance. Thus, overexpression of miR-449b decreases TGFBI, thereby altering the balance between TGFBI and pro-TGFbeta1, revealing a novel mechanism of chemoresistance in NPC. PMID- 29795280 TI - Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1. AB - Piezo proteins are transmembrane ion channels which transduce many forms of mechanical stimuli into electrochemical signals. Their pore, formed by the assembly of three identical subunits, opens by an unknown mechanism. Here, to probe this mechanism, we investigate the interaction of Piezo1 with the small molecule agonist Yoda1. By engineering chimeras between mouse Piezo1 and its Yoda1-insensitive paralog Piezo2, we first identify a minimal protein region required for Yoda1 sensitivity. We next study the effect of Yoda1 on heterotrimeric Piezo1 channels harboring wild type subunits and Yoda1-insensitive mutant subunits. Using calcium imaging and patch-clamp electrophysiology, we show that hybrid channels harboring as few as one Yoda1-sensitive subunit exhibit Yoda1 sensitivity undistinguishable from homotrimeric wild type channels. Our results show that the Piezo1 pore remains fully open if only one subunit remains activated. This study sheds light on the gating and pharmacological mechanisms of a member of the Piezo channel family. PMID- 29795282 TI - Author Correction: Variation in diagnostic test requests and outcomes: a preliminary metric for OpenPathology.net. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. PMID- 29795281 TI - Laminin gamma3 plays an important role in retinal lamination, photoreceptor organisation and ganglion cell differentiation. AB - Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin alpha1, alpha5, beta1, beta2 and gamma1 to be predominantly expressed in Bruch's membrane and the inner limiting membrane. Laminin-332 and laminin gamma3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin gamma3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin gamma3 during human retinogenesis. PMID- 29795283 TI - Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. AB - Psoriasis and parapsoriasis en plaques are chronic inflammatory skin diseases, both representing therapeutic challenge in daily practice and adversely affecting the quality of life. Reactive oxygen species (ROS) has been evidenced to be involved in the pathogenesis of the chronic inflammatory diseases. We now report that hydrogen water, an effective ROS scavenger, has significant and rapid improvement in disease severity and quality of life for patients with psoriasis and parapsoriasis en plaques. At week 8, our parallel-controlled trial revealed 24.4% of patients (10/41) receiving hydrogen-water bathing achieved at least 75% improvement in Psoriasis Area Severity Index (PASI) score compared with 2.9% of patients (1/34) of the control group (Pc = 0.022, OR = 0.094, 95%CI = [0.011, 0.777]). Of patients, 56.1% (23/41) who received bathing achieved at least 50% improvement in PASI score compared with only 17.7%(6/34) of the control group (P = 0.001, OR = 0.168, 95%CI = [0.057, 0.492]). The significant improvement of pruritus was also observed (P = 3.94 * 10-4). Besides, complete response was observed in 33.3% of patients (2/6) of parapsoriasis en plaques and partial response in 66.7% (4/6) at week 8. Our findings suggested that hydrogen-water bathing therapy could fulfill the unmet need for these chronic inflammatory skin diseases. PMID- 29795284 TI - Complete microtubule-kinetochore occupancy favours the segregation of merotelic attachments. AB - Kinetochores are multi-protein complexes that power chromosome movements by tracking microtubules plus-ends in the mitotic spindle. Human kinetochores bind up to 20 microtubules, even though single microtubules can generate sufficient force to move chromosomes. Here, we show that high microtubule occupancy at kinetochores ensures robust chromosome segregation by providing a strong mechanical force that favours segregation of merotelic attachments during anaphase. Using low doses of the microtubules-targeting agent BAL27862 we reduce microtubule occupancy and observe that spindle morphology is unaffected and bi oriented kinetochores can still oscillate with normal intra-kinetochore distances. Inter-kinetochore stretching is, however, dramatically reduced. The reduction in microtubule occupancy and inter-kinetochore stretching does not delay satisfaction of the spindle assembly checkpoint or induce microtubule detachment via Aurora-B kinase, which was so far thought to release microtubules from kinetochores under low stretching. Rather, partial microtubule occupancy slows down anaphase A and increases incidences of lagging chromosomes due to merotelically attached kinetochores. PMID- 29795285 TI - Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double negative T cells. AB - CD4+ T-cell-converted CD4-CD8- double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that the OX40 molecule was highly expressed on cDNT. The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. OX40 promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-kappaB cell signaling played an important role in the transmission of essential division and survival signals through OX40 in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of the OX40 molecule. IL-2 promoted OX40 expression via downregulating the PPARalpha expression. In conclusion, we elucidated that OX40 is a key molecule that regulates cDNT proliferation and survival. IL-2 promoted OX40 expression by downregulating the PPARalpha binding to the OX40 promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT. PMID- 29795286 TI - Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy. AB - Cell-free DNA (cfDNA), which is primarily released following cell death, has been described and developed to serve as an effective biomarker in autoimmune diseases which may share the pathogenesis with schizophrenia. In this study, we hypothesized and explored whether the concentrations and size distributions of cfDNA are abnormal in schizophrenia. A total of 65 patients with schizophrenia (SZ), 29 patients with mood disorders (MD) and 62 matched healthy controls (HC) were included in the study. Fluorescence correlation spectroscopy was used to assay the molar concentrations and size distributions of cfDNA. Fluorometric quantification and quantitative real-time PCR (qPCR) were performed to verify the results. The cfDNA levels were approximately two-fold higher in the SZ group ((29 +/- 15) nM) than in the healthy controls ((15 +/- 9) nM; P-value = 0.00062), but the levels in patients with MD were not significantly different from those in the healthy controls ((17 +/- 10) nM; P-value = 0.343). According to the size distribution analysis, cfDNA in schizophrenia patients was composed of shorter DNA molecules and showed an apoptosis-like distribution pattern. Our study shows the elevated levels and short sizes of cfDNA in schizophrenia patients, which provide direct evidences supporting increased apoptotic activity in the disease. cfDNA may be developed to serve as an auxiliary diagnostic marker for the disease in the future. PMID- 29795287 TI - Identification of the miRNAome of early mesoderm progenitor cells and cardiomyocytes derived from human pluripotent stem cells. AB - MicroRNAs are small non-coding RNAs involved in post-transcriptional regulation of gene expression related to many cellular functions. We performed a small RNAseq analysis of cardiac differentiation from pluripotent stem cells. Our analyses identified some new aspects about microRNA expression in this differentiation process. First, we described a dynamic expression profile of microRNAs where some of them are clustered according to their expression level. Second, we described the extensive network of isomiRs and ADAR modifications. Third, we identified the microRNAs families and clusters involved in the establishment of cardiac lineage and define the mirRNAome based on these groups. Finally, we were able to determine a more accurate miRNAome associated with cardiomyocytes by comparing the expressed microRNAs with other mature cells. MicroRNAs exert their effect in a complex and interconnected way, making necessary a global analysis to better understand their role. Our data expands the knowledge of microRNAs and their implications in cardiomyogenesis. PMID- 29795288 TI - Assessment of Central Visual Function in Patients with Retinitis Pigmentosa. AB - In order to clarify the disease progression in retinitis pigmentosa (RP) and its related factors, reliable data on the changes in central visual function in RP are needed. In this longitudinal study, we examined 118 patients who were diagnosed with typical RP. Visual acuity (VA), visual field using a Humphrey Field Analyzer with the central 10-2 SITA-Standard program, and optical coherence tomography measurements were obtained. The slopes, which were derived from serial values of mean deviation (MD), macular sensitivity (MS), or foveal sensitivity (FS) obtained for each eye by a linear mixed model, were used for analysis. MS and FS were calculated as the average retinal sensitivity of 12 and 4 central points respectively. There were statistically significant interactions of times with levels of the central subfield thickness (CST) on the slopes of MS and FS. Compared to the eyes without macular complications, the eyes with macular complications had steeper MD, MS and FS slopes, and this interaction was no significant, but marginal trend for the MS or FS slope (P = 0.10, 0.05, respectively). The central retinal sensitivity (i.e., MS and FS) slopes calculated were effective indices of the progression of central visual function in RP. PMID- 29795290 TI - Brain APOE expression quantitative trait loci-based association study identified one susceptibility locus for Alzheimer's disease by interacting with APOE epsilon4. AB - Some studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479 normal controls from 12 cohorts of NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). 34 unrelated brain eQTLs for APOE were compiled from BRAINEAC and GTEx. We used multi-covariate logistic regression analysis to identify eQTLs interacted with APOE epsilon4. Adjusted for age and gender, substantia nigra eQTL rs438811 for APOE showed significantly strong interaction with APOE epsilon4 status (OR, 1.448; CI, 1.124-1.430; P-value = 7.94 * 10-6). APOE epsilon4-based sub-group analyses revealed that carrying one minor allele T of rs438811 can increase the opportunity of developing to AD by 26.75% in APOE epsilon4 carriers but not in non-carriers. We revealed substantia nigra eQTL rs438811 for APOE can interact with APOE epsilon4 and confers risk in APOE epsilon4 carriers only. PMID- 29795289 TI - Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair. AB - Yeast Rad1-Rad10 (XPF-ERCC1 in mammals) incises UV, oxidation, and cross-linking agent-induced DNA lesions, and contributes to multiple DNA repair pathways. To determine how Rad1-Rad10 catalyzes inter-strand crosslink repair (ICLR), we examined sensitivity to ICLs from yeast deleted for SAW1 and SLX4, which encode proteins that interact physically with Rad1-Rad10 and bind stalled replication forks. Saw1, Slx1, and Slx4 are critical for replication-coupled ICLR in mus81 deficient cells. Two rad1 mutations that disrupt interactions between Rpa1 and Rad1-Rad10 selectively disable non-nucleotide excision repair (NER) function, but retain UV lesion repair. Mutations in the analogous region of XPF also compromised XPF interactions with Rpa1 and Slx4, and are proficient in NER but deficient in ICLR and direct repeat recombination. We propose that Rad1-Rad10 makes distinct contributions to ICLR depending on cell cycle phase: in G1, Rad1 Rad10 removes ICL via NER, whereas in S/G2, Rad1-Rad10 facilitates NER independent replication-coupled ICLR. PMID- 29795291 TI - TGF-beta concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration. AB - Controversy still exists regarding the role of the TGF-beta in neovascular age related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-beta1, TGF-beta2, and TGF-beta3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-beta pathway activation. Active TGF-beta1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-beta2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-beta3 concentration were found among the sample groups. Moreover, TGF-beta pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-beta2 in nAMD. This should be considered from the perspective of a therapy using TGF-beta inhibitors. PMID- 29795292 TI - Self-selection of dissipative assemblies driven by primitive chemical reaction networks. AB - Life is a dissipative nonequilibrium structure that requires constant consumption of energy to sustain itself. How such an unstable state could have selected from an abiotic pool of molecules remains a mystery. Here we show that liquid phase separation offers a mechanism for the selection of dissipative products from a library of reacting molecules. We bring a set of primitive carboxylic acids out of-equilibrium by addition of high-energy condensing agents. The resulting anhydrides are transiently present before deactivation via hydrolysis. We find the anhydrides that phase-separate into droplets to protect themselves from hydrolysis and to be more persistent than non-assembling ones. Thus, after several starvation-refueling cycles, the library self-selects the phase separating anhydrides. We observe that the self-selection mechanism is more effective when the library is brought out-of-equilibrium by periodic addition of batches as opposed to feeding it continuously. Our results suggest that phase separation offers a selection mechanism for energy dissipating assemblies. PMID- 29795294 TI - Electric switching of magnetism in 2D. PMID- 29795293 TI - Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity. AB - Breast cancer arises from breast epithelial cells that acquire genetic alterations leading to subsequent loss of tissue homeostasis. Several distinct epithelial subpopulations have been proposed, but complete understanding of the spectrum of heterogeneity and differentiation hierarchy in the human breast remains elusive. Here, we use single-cell mRNA sequencing (scRNAseq) to profile the transcriptomes of 25,790 primary human breast epithelial cells isolated from reduction mammoplasties of seven individuals. Unbiased clustering analysis reveals the existence of three distinct epithelial cell populations, one basal and two luminal cell types, which we identify as secretory L1- and hormone responsive L2-type cells. Pseudotemporal reconstruction of differentiation trajectories produces one continuous lineage hierarchy that closely connects the basal lineage to the two differentiated luminal branches. Our comprehensive cell atlas provides insights into the cellular blueprint of the human breast epithelium and will form the foundation to understand how the system goes awry during breast cancer. PMID- 29795295 TI - Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates. AB - Topical microbicides are being explored as an HIV prevention method for individuals who practice receptive anal intercourse. In vivo studies of these microbicides are critical to confirm safety. Here, we evaluated the impact of a rectal microbicide containing the antiviral lectin, Griffithsin (GRFT), on the rectal mucosal proteome and microbiome. Using a randomized, crossover placebo controlled design, six rhesus macaques received applications of hydroxyethylcellulose (HEC)- or carbopol-formulated 0.1% GRFT gels. Rectal mucosal samples were then evaluated by label-free tandem MS/MS and 16 S rRNA gene amplicon sequencing, for proteomics and microbiome analyses, respectively. Compared to placebo, GRFT gels were not associated with any significant changes to protein levels at any time point (FDR < 5%), but increased abundances of two common and beneficial microbial taxa after 24 hours were observed in HEC-GRFT gel (p < 2E-09). Compared to baseline, both placebo formulations were associated with alterations to proteins involved in proteolysis, activation of the immune response and inflammation after 2 hours (p < 0.0001), and increases in beneficial Faecalibacterium spp. after 24 hours in HEC placebo gel (p = 4.21E-15). This study supports the safety profile of 0.1% GRFT gel as an anti-HIV microbicide and demonstrates that current placebo formulations may associate with changes to rectal proteome and microbiota. PMID- 29795296 TI - Ochratoxin A reduction ability of biocontrol agent Bacillus subtilis isolated from Korean traditional fermented food Kimchi. AB - In the present study, a new biocontrol strain, Bacillus subtilis KU-153, was isolated from the Korean traditional fermented food Kimchi and evaluated for its ability to reduce the ochratoxin A (OTA) content in culture medium. A 16 S rRNA gene sequencing analysis revealed the identity of newly isolated strain KU-153 as B. subtilis. The growth kinetic study of B. subtilis KU-153, in terms of the OTA reduction in culture medium, confirmed its biocontrol efficacy. To verify its ability to reduce the OTA content in culture medium, bacterial extracts (intracellular and extracellular) of B. subtilis were separated and compared with whole B. subtilis cells (viable and heat-killed). No reduction in the OTA content was observed in culture medium with extracellular and intracellular extracts, while viable and heat-killed cells of B. subtilis showed significant levels (p < 0.05) of OTA reduction in culture medium. Interestingly, B. subtilis heat-treated cells showed a higher OTA reduction (45%) than viable cells (22%). Further, B. subtilis heat-treated cells were assessed for their ability to reduce OTA levels in artificially contaminated red wine samples that resulted in an OTA reduction of approximately 90%, suggesting the biocontrol potential of the newly isolated strain B. subtilis KU-153 on OTA reduction. PMID- 29795297 TI - An integrated model of gene-culture coevolution of language mediated by phenotypic plasticity. AB - In this paper, we propose an agent-based model for investigating possible scenarios of genetic and cultural language evolution based on an integrated gene culture coevolutionary framework. We focused on the following problems: (1) how communicative ability can evolve directionally under positive frequency-dependent selection and (2) how much of the directional effect there is between language and biological evolution. In our evolutionary experiments and analysis, we discovered a coevolutionary scenario involving the biological evolution of phenotypic plasticity and a cyclic coevolutionary dynamic between genetic and cultural evolution that is mediated by phenotypic plasticity. Furthermore, we discovered that the rates of cultural change are usually faster than the biological rates and fluctuate on a short time scale; on a long time scale, however, cultural rates tend to be slow. This implies that biological evolution can maintain the pace with language evolution. Finally, we analyzed the transfer entropy for a quantitative discussion of the directional effects between both evolutions. The results showed that biological evolution appears to be unable to maintain the pace with language evolution on short time scales, while their mutual directional effects are in the same range on long time scales. This implies that language and the relevant biology could coevolve. PMID- 29795298 TI - Controlling invasive ant species: a theoretical strategy for efficient monitoring in the early stage of invasion. AB - Invasion by the red imported fire ant, Solenopsis invicta Buren, has destructive effects on native biodiversity, agriculture and public health. This ant's aggressive foraging behaviour and high reproductive capability have enabled its establishment of wild populations in most regions into which it has been imported. An important aspect of eradication is thorough nest monitoring and destruction during early invasion to prevent range expansion. The question is: How intense must monitoring be on temporal and spatial scales to eradicate the fire ant? Assuming that the ant was introduced into a region and that monitoring was conducted immediately after nest detection in an effort to detect all other potentially established nests, we developed a mathematical model to investigate detection rates. Setting the monitoring limit to three years, the detection rate was maximized when monitoring was conducted shifting bait trap locations and setting them at intervals of 30 m for each monitoring. Monitoring should be conducted in a radius of at least 4 km around the source nest, or wider-depending on how late a nest is found. For ease of application, we also derived equations for finding the minimum bait interval required in an arbitrary ant species for thorough monitoring. PMID- 29795300 TI - Distribution of tetraether lipids in sulfide chimneys at the Deyin hydrothermal field, southern Mid-Atlantic Ridge: Implication to chimney growing stage. AB - This study presents analysis of four chimney samples in terms of glycerol dialkyl glycerol tetraether lipids (GDGTs), representing different growing stages of sulfide chimneys at the Deyin hydrothermal field, the southern mid-Atlantic ridge. The modified Bligh-Dyer method was used for lipid extraction and purification. GDGTs were analyzed with an Agilent 1200 series liquid chromatograph and 6460A triple quadrupole mass spectrometer. Our results showed that the intact polar GDGTs were more abundant than the core GDGTs in the 4 samples. The intact polar isoprenoidal GDGT-0 was the dominant composition (>70% of isoprenoidal GDGTs), indicating input of thermophilic Euryarchaeota. Most branched GDGTs were likely originated from the in situ thermophilic bacteria. However, the intact polar GDGTs in the sample at the late growing stage was similar to that in normal marine sediments, suggesting that the archaea mainly came from the planktonic Thaumarchaeota input. Our results suggested that the ratio of H-GDGTs to iGDGTs could be considered as a proxy to differentiated growing stages of a chimney. This study shed light on how to assess hydrothermal venting and sulfide chimneys in deep marine environments with a biomarker method in terms of different groups of GDGTs. PMID- 29795299 TI - Raphidocelis subcapitata (=Pseudokirchneriella subcapitata) provides an insight into genome evolution and environmental adaptations in the Sphaeropleales. AB - The Sphaeropleales are a dominant group of green algae, which contain species important to freshwater ecosystems and those that have potential applied usages. In particular, Raphidocelis subcapitata is widely used worldwide for bioassays in toxicological risk assessments. However, there are few comparative genome analyses of the Sphaeropleales. To reveal genome evolution in the Sphaeropleales based on well-resolved phylogenetic relationships, nuclear, mitochondrial, and plastid genomes were sequenced in this study. The plastid genome provides insights into the phylogenetic relationships of R. subcapitata, which is located in the most basal lineage of the four species in the family Selenastraceae. The mitochondrial genome shows dynamic evolutionary histories with intron expansion in the Selenastraceae. The 51.2 Mbp nuclear genome of R. subcapitata, encoding 13,383 protein-coding genes, is more compact than the genome of its closely related oil-rich species, Monoraphidium neglectum (Selenastraceae), Tetradesmus obliquus (Scenedesmaceae), and Chromochloris zofingiensis (Chromochloridaceae); however, the four species share most of their genes. The Sphaeropleales possess a large number of genes for glycerolipid metabolism and sugar assimilation, which suggests that this order is capable of both heterotrophic and mixotrophic lifestyles in nature. Comparison of transporter genes suggests that the Sphaeropleales can adapt to different natural environmental conditions, such as salinity and low metal concentrations. PMID- 29795301 TI - Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages. AB - Diverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how Histoplasma capsulatum load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus' EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from H. capsulatum opsonized with 6B7 was reduced, but urease activity was not altered. The uptake of H. capsulatum by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized H. capsulatum and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies H. capsulatum EV load and secretion leading to distinct effects on the host's immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells. PMID- 29795302 TI - HDV infection rates in northern Vietnam. AB - Hepatitis D caused by the hepatitis delta virus (HDV) is a serious health problem in many regions of the world. A total of 546 HBV-infected patients were enrolled from 2013 to 2015 and classified clinically into the subgroups of chronic hepatitis B (CHB, n = 191), liver cirrhosis (LC, n = 147) and hepatocellular carcinoma (HCC, n = 208). The patients were screened for HDV-RNA by nested PCR assays. HDV genotypes were assessed by direct sequencing, followed by phylogenetic analysis. HDV-RNA was identified in 13% (71/546) of HBV-infected patients. The highest HDV prevalence was found in the LC group (19.7%), followed by the HCC (12%) and CHB (8.9%) groups (P = 0.017). HDV/HBV coinfections were significantly associated with a rather unfavourable clinical outcome, in particular with LC development compared to HBV monoinfection. Phylogenetic analyses indicated that the genotype HDV1 was, with a prevalence of 91%, by far the most common genotype in Vietnam, followed by HDV2 with 9%. Other HDV genotypes were not observed. In accordance with previous data obtained a decade ago, our results confirm a continuing high prevalence of HDV infection in hepatitis B patients in northern Vietnam with the HDV1 genotype still being the predominant genotype. HDV nucleic acid testing to minimize the associated risk should be considered. PMID- 29795303 TI - Prevalence and Associations of Illicit Drug and Polydrug Use in People Living with HIV in Vienna. AB - We aimed to determine the prevalence of drug and polydrug use in people living with HIV in Austria for the first time for which a two center cross-sectional study was performed. Participants were recruited from consecutive patients during their regularly scheduled visits. In total 438 participants were included in the analysis. For this study we used paper-pencil and online-based questionnaires. The prevalence of illicit drug use was 60.5%; with cannabis use at 31.5%, nitrates at 31.5%, sildenafil/tadalafil at 24% and cocaine at 14%, being the most used substances. Use of more than one substance (polydrug) in drug users was 69.4% or 42.0% in the total study population. Younger age, male gender, and living in an urban area were associated with drug use. Moreover, drug use during clubbing and sex, HIV therapy non-adherence and younger age were associated with polydrug use. Drug users reported condomless sex in 42.4% and performing sexual acts they would not do sober in 44.1%. Results indicate a high prevalence of illicit drug use in PLWHIV in Austria. New research focusing on illicit drug use in PLWHIV should focus on the use of substances during sex and surrounding practices. PMID- 29795304 TI - NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population. AB - Approximately 10-20% of patients with primary biliary cholangitis (PBC) progress to jaundice stage regardless of treatment with ursodeoxycholic acid and bezafibrate. In this study, we performed a GWAS and a replication study to identify genetic variants associated with jaundice-stage progression in PBC using a total of 1,375 patients (1,202 early-stage and 173 jaundice-stage) in a Japanese population. SNP rs13720, which is located in the 3'UTR of cathepsin Z (CTSZ), showed the strongest association (odds ratio [OR] = 2.15, P = 7.62 * 10 7) with progression to jaundice stage in GWAS. High-density association mapping at the CTSZ and negative elongation factor complex member C/D (NELFCD) loci, which are located within a strong linkage disequilibrium (LD) block, revealed that an intronic SNP of CTSZ, rs163800, was significantly associated with jaundice-stage progression (OR = 2.16, P = 8.57 * 10-8). In addition, eQTL analysis and in silico functional analysis indicated that genotypes of rs163800 or variants in strong LD with rs163800 influence expression levels of both NELFCD and CTSZ mRNA. The present novel findings will contribute to dissect the mechanism of PBC progression and also to facilitate the development of therapies for PBC patients who are resistant to current therapies. PMID- 29795305 TI - Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells. AB - Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo. After infection of Ad-E6/E7-AS, the cellular growth of UM-SCC-47 cells were suppressed, but not that of YCU-T892 cells. E7 protein expression was suppressed, and p53 and pRb protein expression increased after infection of Ad-E7-AS. Cell growth and tumorigenicity were greatly suppressed in combination with CDDP compared with Ad E7-AS or CDDP treatment alone in vitro. Ad-E7-AS combined with CDDP treatment significantly reduced the volumes of established subcutaneous tumors. Transfection with HPV 16 E7 antisense RNA combined with CDDP treatment might be a potentially useful approach to the therapy of HPV 16-positive HNC. PMID- 29795307 TI - The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma. AB - BACKGROUND: The outcome of patients who progress on front-line immune-based combination regimens (IC) including immune checkpoint inhibitors (CPI) and receive subsequent systemic therapy is unknown. METHODS: Retrospective analysis of consecutive patients with clear-cell mRCC who progressed on one of seven clinical trials investigating an IC and received >=1 line of subsequent VEGFR TKI therapy. RESULTS: Thirty-three patients [median age 57 (37-77), 85% male, 73% ECOG 0] were included. For evaluable patients (N = 28), the best response to first subsequent therapy was 29% partial response, 54% stable disease, and 18% progressive disease. The median PFS (mPFS) for first subsequent therapy was 6.4 months (95% CI, 4.4-8.4); no difference in mPFS by prior type of IC (VEGFR TKI CPI vs. CPI-CPI) was noted (p = 0.310). Significant AEs were observed in 30% of patients, more frequently transaminitis (9%). CONCLUSIONS: VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy. PMID- 29795308 TI - Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials. AB - BACKGROUND: We examined the impact of race on the maximum tolerated doses (MTD) and final approved doses (FAD) of single-agent molecular-targeted agents (MTA) in North America/Europe (NA/EU) and Asia. METHODS: We searched PubMed and regulatory databases to identify targeted drugs approved globally and compared their FAD and MTD in corresponding phase I/II studies conducted separately in NA/EU and Asia. To evaluate this further, we conducted parallel, prospective, first-in-human studies of DS-7423, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumours in the US and Japan. We pooled and compared the pharmacokinetics (PK), pharmacodynamics (PD), toxicity, and efficacy between these populations. RESULTS: 17 MTA were approved in NA/EU and Asia from 2001 to 2015. Recommended phase 2 doses (RP2D) were identical across races in 14 of 17 (80%) studies and differences were not clinically meaningful. FAD were identical across all regions. 42 and 27 patients from US and Japan, respectively, were enrolled in the phase I studies of DS-7423. Despite differences in race, body weight, and body mass index, the RP2D were 240 mg/day with no differences in toxicities, PK, PD, or efficacy. CONCLUSIONS: Conducting separate clinical trials of single-agent MTA in Caucasian and Asian populations may be redundant. PMID- 29795306 TI - Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. AB - BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94 1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk. PMID- 29795309 TI - Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams). AB - BACKGROUND: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries. METHODS: Consecutive OPSCC patients treated in Denmark, 2000-2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. RESULTS: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. CONCLUSIONS: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org . PMID- 29795310 TI - The sVEGFR1-i13 splice variant regulates a beta1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma. AB - BACKGROUND: While lung adenocarcinoma patients can somewhat benefit from anti angiogenic therapies, patients with squamous cell lung carcinoma (SQLC) cannot. The reasons for this discrepancy remain largely unknown. Soluble VEGF receptor-1, namely sVEGFR1-i13, is a truncated splice variant of the cell membrane-spanning VEGFR1 that has no transmembrane or tyrosine kinase domain. sVEGFR1-i13 is mainly viewed as an anti-angiogenic factor which counteracts VEGF-A/VEGFR signalling in endothelial cells. However, its role in tumour cells is poorly known. METHODS: mRNA and protein status were analysed by Real-Time qPCR, western blotting, ELISA assay, proximity ligation assay or immunohistochemistry in human tumour cell lines, murine tumourgrafts and non small cell lung carcinoma patients samples. RESULTS: We show that anti-angiogenic therapies specifically increase the levels of sVEGFR1-i13 in SQLC cell lines and chemically induced SQLC murine tumourgrafts. At the molecular level, we characterise a sVEGFR1-i13/beta1 integrin/VEGFR autocrine loop which determines whether SQLC cells proliferate or go into apoptosis, in response to anti-angiogenic therapies. Furthermore, we show that high levels of both sVEGFR1-i13 and beta1 integrin mRNAs and proteins are associated with advanced stages in SQLC patients and with a poor clinical outcome in patients with early stage SQLC. CONCLUSIONS: Overall, these results reveal an unexpected pro-tumoural function of sVEGFR1-i13 in SQLC tumour cells, which contributes to their progression and escape from anti-angiogenic therapies. These data might help to understand why some SQLC patients do not respond to anti angiogenic therapies. PMID- 29795311 TI - DNMT1 mediates metabolic reprogramming induced by Epstein-Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma. AB - Cancer cells frequently adapt fundamentally altered metabolism to support tumorigenicity and malignancy. Epigenetic and metabolic networks are closely interactive, in which DNA methyltransferases (DNMTs) play important roles. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (EBV-LMP1) is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis because it can trigger multiple cell signaling pathways that promote cell transformation, proliferation, immune escape, invasiveness, epigenetic modification, and metabolic reprogramming. Our current findings reveal for the first time that LMP1 not only upregulates DNMT1 expression and activity, but also promotes its mitochondrial translocation. This induces epigenetic silencing of pten and activation of AKT signaling as well as hypermethylation of the mtDNA D-loop region and downregulation of oxidative phosphorylation (OXPHOS) complexes, consequently, leading to metabolic reprogramming in NPC. Furthermore, we demonstrate that grifolin, a natural farnesyl phenolic compound originated from higher fungi, is able to attenuate glycolytic flux and recover mitochondrial OXPHOS function by inhibiting DNMT1 expression and activity as well as its mitochondrial retention in NPC cells. Therefore, our work establishes a mechanistic connection between epigenetics and metabolism in EBV-positive NPC and provides further evidence for pathological classification based on CpG island methylator phenotype (CIMP) in EBV-associated malignancies. In addition, grifolin might be a promising lead compound in the intervention of high-CIMP tumor types. The availability of this natural product could hamper tumor cell metabolic reprogramming by targeting DNMT1. PMID- 29795312 TI - A 2-transcript host cell signature distinguishes viral from bacterial diarrhea and it is influenced by the severity of symptoms. AB - Recently, a biomarker signature consisting of 2-transcript host RNAs was proposed for discriminating bacterial from viral infections in febrile children. We evaluated the performance of this signature in a different disease scenario, namely a cohort of Mexican children (n = 174) suffering from acute diarrhea of different infectious etiologies. We first examined the admixed background of the patients, indicating that most of them have a predominantly Native American genetic ancestry with a variable amount of European background (ranging from 0% to 57%). The results confirm that the RNA test can discriminate between viral and bacterial causes of infection (t-test; P-value = 6.94*10-11; AUC = 80%; sensitivity: 68% [95% CI: 55%-79%]; specificity: 84% [95% CI: 78%-90%]), but the strength of the signal differs substantially depending on the causal pathogen, with the stronger signal being that of Shigella (P-value = 3.14 * 10-12; AUC = 89; sensitivity: 70% [95% CI: 57%-83%]; specificity: 100% [95% CI: 100%-100%]). The accuracy of this test improves significantly when excluding mild cases (P value = 2.13 * 10-6; AUC = 85%; sensitivity: 79% [95% CI: 58%-95%]; specificity: 78% [95% CI: 65%-88%]). The results broaden the scope of previous studies by incorporating different pathogens, variable levels of disease severity, and different ancestral background of patients, and add confirmatory support to the clinical utility of these 2-transcript biomarkers. PMID- 29795313 TI - Novel human microbe-disease associations inference based on network consistency projection. AB - Increasing evidence shows that microbes are closely related to various human diseases. Obtaining a comprehensive and detailed understanding of the relationships between microbes and diseases would not only be beneficial to disease prevention, diagnosis and prognosis, but also would lead to the discovery of new drugs. However, because of a lack of data, little effort has been made to predict novel microbe-disease associations. To date, few methods have been proposed to solve the problem. In this study, we developed a new computational model based on network consistency projection to infer novel human microbe disease associations (NCPHMDA) by integrating Gaussian interaction profile kernel similarity of microbes and diseases, and symptom-based disease similarity. NCPHMDA is a non-parametric and global network based model that combines microbe space projection and disease space projection to achieve the final prediction. Experimental results demonstrated that the integrated space projection of microbes and diseases, and symptom-based disease similarity played roles in the model performance. Cross validation frameworks and case studies further illustrated the superior predictive performance over other methods. PMID- 29795314 TI - The window of improved neonatal respiratory compliance after rescue antenatal steroids. AB - OBJECTIVE: To evaluate whether premature infants delivered <=7 days after rescue antenatal steroid treatment (ideal treatment) have increased passive respiratory compliance compared to those delivered >7 days after treatment (remote treatment). METHODS: Secondary analysis of a randomized trial of rescue antenatal steroids on respiratory compliance. Infants in the treatment group were stratified by the interval between rescue antenatal steroids and delivery. We then compared the respiratory compliance in the ideal vs. remote groups. RESULTS: Forty-four women (56 infants) received rescue antenatal steroids. Forty-nine infants had evaluable respiratory compliance measurements, with 27 (GA 30.1 weeks, BW 1362 g) "ideally" treated, and 22 (GA 33.8 weeks, BW 2248 g) "remotely" treated. Respiratory compliance was significantly higher for the ideal compared to the remote group (1.32 vs. 1.06 mL/cm H2O/kg; p = 0.037). CONCLUSION: Infants treated with rescue antenatal steroids have a significantly higher respiratory compliance if delivery occurs within 7 days after treatment. PMID- 29795316 TI - The amount of supervision trainees receive during neonatal resuscitation is variable and often dependent on subjective criteria. AB - OBJECTIVE: Measure variation in delivery room supervision provided by neonatologists using hypothetical scenarios and determine the factors used to guide entrustment decisions. STUDY DESIGN: A survey was distributed to members of the American Academy of Pediatrics Section on Perinatal Pediatrics. Neonatologists were presented with various newborn resuscitation scenarios and asked to choose the level of supervision they thought appropriate and grade factors on their importance in making entrustment decisions. RESULTS: There was significant variation in supervision neonatologists deemed necessary for most scenarios (deviation from the mode 0.36-0.69). Post-graduate year of training and environmental circumstances influence the amount of autonomy neonatologists grant trainees. Few neonatologists have objective assessment of a trainees' competence in neonatal resuscitation available to them and most never document how the trainee performed. CONCLUSION: Delivery room supervision is often determined by subjective evaluation of trainees' competence and may not provide a level of supervision congruent with their capability. PMID- 29795317 TI - In Response to Letter from Altit, Basso, Grandi, and Yang. PMID- 29795315 TI - Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy. AB - OBJECTIVE: To evaluate the association between sedation-analgesia (SA) during initial 72 h and death/disability at 18 months of age in neonatal hypoxic ischemic encephalopathy (HIE). DESIGN: This was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72 h of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or Gross Motor Function Classification System 2-5. RESULTS: Of the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the five time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at >=3 time points; 72% infants received anticonvulsants during 72 h of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88), and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability, whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome. CONCLUSIONS: The risk benefits of SA in HIE need further investigation. PMID- 29795319 TI - Response to Letter to the Editor. PMID- 29795318 TI - Association of admission temperature and death or adverse neurodevelopmental outcomes in extremely low-gestational age neonates. AB - OBJECTIVE: Preterm infants are at higher risk of developing hypothermia and complications from cold stress, resulting in high mortality and short-term morbidity. Our objective is to evaluate the association between admission temperatures of extremely low-gestational age neonates (ELGAN) (<29 weeks') and adverse short-term neurodevelopmental outcomes. STUDY DESIGN: In this retrospective study, we included ELGAN admitted to NICUs across Canada between April 2009 and September 2011, who underwent neurodevelopmental assessment at 18 21 months' corrected age. RESULTS: Of 2739 infants with a complete data set identified during the study period, 968 (35.3%) had admission temperatures <=36.4 degrees C (hypothermia group), 1489 (54.5%) had temperature of 36.5-37.2 degrees C (normothermia group), and 282 (10.3%) had hyperthermia (>=37.3 degrees C). Their mean birth weight was 823 +/- 230 g, 944 +/- 227 g and 927 +/- 223 g, respectively (p < 0.01). More than 50% of infants born at 23-24 weeks were in the hypothermic group compared to 28.5-36.1% at higher gestational ages. We found 39.5% of infants in the hypothermic group had primary composite outcome of death or severe neurodevelopmental impairment (sNDI). Multivariate logistic regression revealed an increased adjusted odd of primary composite outcome (OR = 1.32; 95% CI = [1.05, 1.66]) in the hypothermic group, compared to infants with normothermia on admission. CONCLUSIONS: In our cohort of ELGAN, hypothermia on admission was associated with increased risk of death or sNDI. PMID- 29795320 TI - The relative effects of patient and hospital factors on postpartum readmissions. AB - OBJECTIVE: To determine the relative effects of patient and hospital factors on a hospital's postpartum readmission rate. STUDY DESIGN: This retrospective cohort study was conducted using State Inpatient Databases from California, Florida, and New York between 2004 and 2013. We compared patient and hospital characteristics among hospitals with low and high readmission rates using chi2 tests. Risk adjusted 30-day readmission rates were calculated for patient, delivery, and hospital characteristics to understand factors affecting readmission using fixed and random effects models. RESULTS: Patients in hospitals with low readmission rates were more likely to be white, to have private insurance and higher incomes, and to have fewer comorbidities. The patient comorbidities with the highest risk adjusted readmission rates included hypertension (range, 2.14-3.04%), obesity (1.78-2.94%), preterm labor/delivery (2.50-2.60%), and seizure disorder (1.78 3.35%). Delivery complications were associated with increased risk-adjusted readmission rates. Compared to patient characteristics, hospital characteristics did not have a profound impact on readmission risk. CONCLUSION: Obstetric readmissions were more attributable to patient and demographic characteristics than to hospital characteristics. Readmission metric-based incentives may ultimately penalize hospitals providing high-quality care due to patient characteristics specific to their catchment area. PMID- 29795322 TI - Introduction to quality improvement tools for the clinician. AB - As physicians continue search for ways to deliver high quality care to their patients and families, newer tools and methods are being introduced. Initially developed by manufacturing, quality improvement methods have been slowly adopted by healthcare and are now standard curriculum in medical schools. The IHI Model for Improvement allows for teams to create. model for change, test proposed changes in clinical situations, measure the results and then accept or modify the proposed changes. Additional tools such as process maps, Pareto charts, Ishikawa diagrams, and key driver diagrams provide structure and visual representation to the team during the creation and implementation of. quality improvement initiative. As participation in quality improvement is becoming an expectation for all health care providers, familiarity with these tools will assist teams with implementing improved processes in their local systems of care. PMID- 29795321 TI - Second trimester serum cortisol and preterm birth: an analysis by timing and subtype. AB - OBJECTIVE: We hypothesized second trimester serum cortisol would be higher in spontaneous preterm births compared to provider-initiated (previously termed 'medically indicated') preterm births. STUDY DESIGN: We used a nested case control design with a sample of 993 women with live births. Cortisol was measured from serum samples collected as part of routine prenatal screening. We tested whether mean-adjusted cortisol fold-change differed by gestational age at delivery or preterm birth subtype using multivariable linear regression. RESULT: An inverse association between cortisol and gestational age category (trend p = 0.09) was observed. Among deliveries prior to 37 weeks, the mean-adjusted cortisol fold-change values were highest for preterm premature rupture of the membranes (1.10), followed by premature labor (1.03) and provider-initiated preterm birth (1.01), although they did not differ statistically. CONCLUSION: Cortisol continues to be of interest as a marker of future preterm birth. Augmentation with additional biomarkers should be explored. PMID- 29795323 TI - In response: Is early onset sepsis risk calculator safe for the management of neonates born to mothers with chorioamnionitis? PMID- 29795324 TI - Resource utilization patterns using non-invasive ventilation in neonates with respiratory distress syndrome. AB - OBJECTIVES: To describe the frequency of non-invasive ventilation (NIV) and endotracheal intubation use in neonates diagnosed with respiratory distress syndrome (RDS); to describe resources utilization (length of stay (LOS), charges, costs) among NIV and intubated RDS groups. STUDY DESIGN: Retrospective study from the national Kid's Inpatient Database of the Healthcare Cost and Utilization Project, for the years 1997-2012. Propensity scoring and multivariate regression analysis used to describe differences. RESULTS: A total of 595,254 out of 42,912,090 cases were identified with RDS. There was an increase in NIV use from 6% in 1997 to 17% in 2012. After matching, patients receiving NIV only were associated with shorter LOS: (95%CI) 25 (25.3,25.7) vs. 35 (34.2,34.9) days, decreased costs: ($/1k) 46.1 (45.5,46.8) vs. 65.0 (64.1,66.0), decreased charges: 130.3 (128.6,132.1) vs. 192.1 (189.5,194.6) compared to intubated neonates. CONCLUSION: There was a three-fold increase in NIV use within the 15-year study period. NIV use was associated with decreased LOS, charges and costs compared to intubated patients. PMID- 29795325 TI - National trends in neonatal extracorporeal membrane oxygenation in the United States. AB - OBJECTIVE: To determine trends in neonatal extracorporeal membrane oxygenation (ECMO) utilization from 2002-2011. STUDY DESIGN: Using the Nationwide inpatient sample (NIS), we conducted a population-based retrospective cohort study to identify ECMO utilization among neonates. Incidence of ECMO utilization, length of stay (LOS), cost and mortality were estimated. RESULT: In all, 33,367,146 neonates were identified of which 7603 (18 per 100,000 live births) underwent ECMO. Neonatal ECMO increased from 12 to 23 runs per 100,000 live births. Mortality was 48.4%, decreasing from 47.5 to 41.9% between 2002 and 2011. On multivariate analysis, mortality was significantly higher for infectious indications (OR 4.1; CI 1.1-16.0), E-CPR (OR 3.8; CI 1.4-10.7) and cardiac indications (OR 2.0; CI 1.5-2.8). On hierarchical regression, LOS increased by 1.6 days each year (p = 0.02) and cost of hospitalization increased by $14,033 each year (p < 0.0001). CONCLUSION: Neonatal ECMO utilization increased, while mortality decreased during the study period. These findings suggest an improvement in neonatal ECMO care. PMID- 29795327 TI - Silent regulators. PMID- 29795328 TI - Best practices for analysing microbiomes. AB - Complex microbial communities shape the dynamics of various environments, ranging from the mammalian gastrointestinal tract to the soil. Advances in DNA sequencing technologies and data analysis have provided drastic improvements in microbiome analyses, for example, in taxonomic resolution, false discovery rate control and other properties, over earlier methods. In this Review, we discuss the best practices for performing a microbiome study, including experimental design, choice of molecular analysis technology, methods for data analysis and the integration of multiple omics data sets. We focus on recent findings that suggest that operational taxonomic unit-based analyses should be replaced with new methods that are based on exact sequence variants, methods for integrating metagenomic and metabolomic data, and issues surrounding compositional data analysis, where advances have been particularly rapid. We note that although some of these approaches are new, it is important to keep sight of the classic issues that arise during experimental design and relate to research reproducibility. We describe how keeping these issues in mind allows researchers to obtain more insight from their microbiome data sets. PMID- 29795326 TI - Adapting to stress - chaperome networks in cancer. AB - In this Opinion article, we aim to address how cells adapt to stress and the repercussions chronic stress has on cellular function. We consider acute and chronic stress-induced changes at the cellular level, with a focus on a regulator of cellular stress, the chaperome, which is a protein assembly that encompasses molecular chaperones, co-chaperones and other co-factors. We discuss how the chaperome takes on distinct functions under conditions of stress that are executed in ways that differ from the one-on-one cyclic, dynamic functions exhibited by distinct molecular chaperones. We argue that through the formation of multimeric stable chaperome complexes, a state of chaperome hyperconnectivity, or networking, is gained. The role of these chaperome networks is to act as multimolecular scaffolds, a particularly important function in cancer, where they increase the efficacy and functional diversity of several cellular processes. We predict that these concepts will change how we develop and implement drugs targeting the chaperome to treat cancer. PMID- 29795329 TI - Integration of Ca2+ signaling regulates the breast tumor cell response to simvastatin and doxorubicin. AB - Recent studies have suggested that the lipid-lowering agent simvastatin holds great promise as a cancer therapeutic; it inhibits the growth of multiple tumors, including triple-negative breast cancer. Doxorubicin- and simvastatin-induced cytotoxicity has been associated with the modulation of Ca2+ signaling, but the underlying mechanisms remain incompletely understood. Here we identify how Ca2+ signaling regulates the breast tumor cell response to doxorubicin and simvastatin. These two drugs inhibit cell survival while increasing apoptosis in two human breast cancer cell lines and five primary breast tumor specimens through the modulation of Ca2+ signaling. Signal transduction and functional studies revealed that both simvastatin and doxorubicin trigger persistent cytosolic Ca2+ release, thereby stimulating the proapoptotic BIM pathway and mitochondrial Ca2+ overload, which are responsible for metabolic dysfunction and apoptosis induction. Simvastatin and doxorubicin suppress the prosurvival ERK1/2 pathway in a Ca2+-independent and Ca2+-dependent manner, respectively. In addition, reduction of the Ca2+ signal by chelation or pharmacological inhibition significantly prevents drug-mediated anticancer signaling. Unexpectedly, a scratch-wound assay indicated that these two drugs induce rapid cell migration, while inhibiting cell invasion and colony formation in a Ca2+-dependent manner. Further, the in vivo data for MDA-MB-231 xenografts demonstrate that upon chelation of Ca2+, the ability of both drugs to reduce the tumor burden was significantly reduced via caspase-3 deactivation. Our results establish a calcium based mechanism as crucial for executing the cell death process triggered by simvastatin and doxorubicin, and suggest that combining simvastatin with doxorubicin may be an effective regimen for the treatment of breast cancer. PMID- 29795330 TI - K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death. AB - Fas-associated death domain (FADD) is an adaptor protein recruiting complexes of caspase 8 to death ligand receptors to induce extrinsic apoptotic cell death in response to a TNF superfamily member. Although, formation of the complex of FADD and caspase 8 upon death stimuli has been studied in detail, posttranslational modifications fine-tuning these processes have yet to be identified. Here we revealed that K6-linked polyubiquitylation of FADD on lysines 149 and 153 mediated by C terminus HSC70-interacting protein (CHIP) plays an important role in preventing formation of the death inducing signaling complex (DISC), thus leading to the suppression of cell death. Cells depleted of CHIP showed higher sensitivity toward death ligands such as FasL and TRAIL, leading to upregulation of DISC formation composed of a death receptor, FADD, and caspase 8. CHIP was able to bind to FADD, induce K6-linked polyubiquitylation of FADD, and suppress DISC formation. By mass spectrometry, lysines 149 and 153 of FADD were found to be responsible for CHIP-mediated FADD ubiquitylation. FADD mutated at these sites was capable of more potent cell death induction as compared with the wild type and was no longer suppressed by CHIP. On the other hand, CHIP deficient in E3 ligase activity was not capable of suppressing FADD function and of FADD ubiquitylation. CHIP depletion in ME-180 cells induced significant sensitization of these cells toward TRAIL in xenograft analyses. These results imply that K6 linked ubiquitylation of FADD by CHIP is a crucial checkpoint in cytokine dependent extrinsic apoptosis. PMID- 29795333 TI - New biomarker predicts disability in MS. PMID- 29795332 TI - Deep brain stimulation boosts motor connectivity. PMID- 29795335 TI - Increased mitochondrial respiration promotes survival from endoplasmic reticulum stress. AB - Protein misfolding in the endoplasmic reticulum (ER) is accompanied by adaptive cellular responses to promote cell survival. We now show that activation of mitochondrial respiration is a critical component of an adaptive ER stress response, requiring the unfolded protein response (UPR) sensor Ire1, and also calcium signaling via calcineurin. In yeast and mammalian cells lacking Ire1 or calcineurin, respiratory activation is impaired in response to ER stress; accumulation of mitochondrial reactive oxygen species (ROS) triggers cell death as abrogation of ROS by antioxidants or loss of the electron transport chain (in yeast) can rescue cells from death. Significantly, cells are rescued from ER stress-induced death by mitochondrial uncoupling by CCCP to increase O2 consumption (and increase the efficiency of electron transfer). Remarkably, genetic and pharmacologic strategies to promote mitochondrial biogenesis and increase O2 consumption also alleviate ER stress-mediated ROS and death in yeast and mammalian cells. Moreover, in a yeast genetic screen, three mitochondrial proteins Mrx9, Mrm1, and Aim19 that increase mitochondrial biogenesis were identified as high copy suppressors of ER stress-mediated cell death. Our results show that enhanced mitochondrial biogenesis, linked to improved efficiency of the electron transport chain, is a powerful strategy to block ROS accumulation and promote cell survival during ER stress in eukaryotic cells. PMID- 29795334 TI - Enhanced breast cancer progression by mutant p53 is inhibited by the circular RNA circ-Ccnb1. AB - TP53 mutations occur in many different types of cancers that produce mutant p53 proteins. The mutant p53 proteins have lost wild-type p53 activity and gained new functions that contribute to malignant tumor progression. Different p53 mutations create distinct profiles in loss of wild-type p53 activity and gain of functions. Targeting the consequences generated by the great number of p53 mutations would be extremely complex. Therefore, in this study we used a workaround and took advantage of the fact that mutant p53 cannot bind H2AX. Using this, we developed a new approach to repress the acquisition of mutant p53 functions. We show here that the delivery of a circular RNA circ-Ccnb1 inhibited the function of three p53 mutations. By microarray analysis and real-time PCR, we detected decreased circ-Ccnb1 expression levels in patients bearing breast carcinoma. Ectopic delivery of circ-Ccnb1 inhibited tumor growth and extended mouse viability. Using proteomics, we found that circ-Ccnb1 precipitated p53 in p53 wild-type cells, but instead precipitated Bclaf1 in p53 mutant cells. Further experiments showed that H2AX serves as a bridge, linking the interaction of circ-Ccnb1 and wild-type p53, thus allowing Bclaf1 to bind Bcl2 resulting in cell survival. In the p53 mutant cells, circ-Ccnb1 formed a complex with H2AX and Bclaf1, resulting in the induction of cell death. We found that this occurred in three p53 mutations. These results shed light on the possible development of new approaches to inhibit the malignancy of p53 mutations. PMID- 29795336 TI - NFkappaB mitigates the pathological effects of misfolded alpha1-antitrypsin by activating autophagy and an integrated program of proteostasis mechanisms. AB - Intrahepatocytic accumulation of misfolded alpha1-antitrypsin Z variant (ATZ) is responsible for liver disease in some individuals with alpha1-antitrypsin deficiency (ATD), characterized by fibrosis/cirrhosis and predisposition to carcinogenesis. Previous results showing that accumulation of ATZ in model systems activates the NFkappaB signaling pathway have led us to hypothesize that downstream targets of NFkappaB are elements of a proteostasis response network for this type of proteinopathy. Here we show that only a subset of downstream targets within the NFkappaB transcriptomic repertoire are activated in model systems of this proteinopathy. Breeding of the PiZ mouse model of ATD to two different mouse models with NFkappaB deficiency led to greater intrahepatocytic accumulation of ATZ, more severe hepatic fibrosis, decreased autophagy and hyperproliferation of hepatocytes with massive ATZ inclusions. Specific downstream targets of NFkappaB could be implicated in each pathological effect. These results suggest a new role for NFkappaB signaling in which specific downstream targets of this pathway mediate an integrated program of proteostatic responses designed to mitigate the pathologic effects of proteinopathy, including autophagic disposal of misfolded protein, degradation of collagen and prevention of hyperproliferation. PMID- 29795337 TI - Cholinergic activity is essential for maintaining the anterograde transport of Choline Acetyltransferase in Drosophila. AB - Cholinergic activity is essential for cognitive functions and neuronal homeostasis. Choline Acetyltransferase (ChAT), a soluble protein that synthesizes acetylcholine at the presynaptic compartment, is transported in bulk in the axons by the heterotrimeric Kinesin-2 motor. Axonal transport of soluble proteins is described as a constitutive process assisted by occasional, non-specific interactions with moving vesicles and motor proteins. Here, we report that an increase in the influx of Kinesin-2 motor and association between ChAT and the motor during a specific developmental period enhances the axonal entry, as well as the anterograde flow of the protein, in the sensory neurons of intact Drosophila nervous system. Loss of cholinergic activity due to Hemicholinium and Bungarotoxin treatments, respectively, disrupts the interaction between ChAT and Kinesin-2 in the axon, and the episodic enhancement of axonal influx of the protein. Altogether, these observations highlight a phenomenon of synaptic activity-dependent, feedback regulation of a soluble protein transport in vivo, which could potentially define the quantum of its pre-synaptic influx. PMID- 29795339 TI - Long noncoding RNAs in the metabolic control of inflammation and immune disorders. AB - The metabolic control of immune cell development and function has been shown to be critical for the maintenance of immune homeostasis and is also involved in the pathogenesis of immune disorders. Pathogenic infections or cancers may induce metabolic reprogramming through different pathways to meet the energy and metabolite demands for pathogen propagation or cancer progression. In addition, some deregulated metabolites could trigger or regulate immune responses, thus causing chronic inflammation or immune disorders, such as viral infection, cancer and obesity. Therefore, the methods through which metabolism is regulated and the role of metabolic regulation in inflammation and immunity attract much attention. Epigenetic regulation of inflammation and immunity is an emerging field. Long noncoding RNAs (lncRNAs) have been well documented to play crucial roles in many biological processes through diverse mechanisms, including immune regulation and metabolic alternation. Here, we review the functions and mechanisms of lncRNAs in the metabolic regulation of inflammatory immune disorders, aiming to deepen our understanding of the epigenetic regulation of inflammation and immunity. PMID- 29795331 TI - Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer. AB - The term metastasis is widely used to describe the endpoint of the process by which tumour cells spread from the primary location to an anatomically distant site. Achieving successful dissemination is dependent not only on the molecular alterations of the cancer cells themselves, but also on the microenvironment through which they encounter. Here, we reviewed the molecular alterations of metastatic gastric cancer (GC) as it reflects a large proportion of GC patients currently seen in clinic. We hope that further exploration and understanding of the multistep metastatic cascade will yield novel therapeutic targets that will lead to better patient outcomes. PMID- 29795338 TI - Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus. AB - Distinct clinical features of HBV infection have been associated with different viral genotype/subgenotype. HBV Genotype-D comprised of 10 subgenotypes, D1-D10, whose clinical implications still remain elusive. We investigated for the first time, the virologic characteristics and cytopathic effects of four non recombinant D-subgenotypes, D1/D2/D3/D5. Expressions of viral/host genes were evaluated in Huh7 cells transfected with full-length, linear-monomers of HBV/D subgenotypes or pGL3-Basic vector carrying subgenotype-specific HBx. Intracellular HBV-DNA and pregenomic-RNA levels were high in D1/D2 than D3/D5. Expressions of PreC-mRNA and HBx were highest for D2 and D1 respectively, whereas PreS2/S-transcript was significantly reduced in D5. Increased apoptotic cell death and marked upregulation in caspase-3/Bax/TNF-R1/FasR/TRAIL-R1/ROS/MCP-1/IP 10/MIP-1beta expression were noticed specifically in D2- and also in D3 transfected cells, while D5 resulted in over-expression of ER-stress-markers. D subgenotype-transfected Huh7 cells were co-cultured with PBMC of healthy-donors or LX-2 cells and significant increase in pro-inflammatory cytokines in PBMC and fibrogenic-markers in LX-2 were noticed in presence of D2/D3. Further, Huh7 cells transfected with D1, in particular and also D5, displayed remarkable induction of EMT-markers and high proliferative/migratory abilities. Collectively, our results demonstrated that D2/D3 were more associated with hepatic apoptosis/inflammation/fibrosis and D1/D5 with increased risk of hepatocarcinogenesis and emphasize the need for determining HBV-subgenotype in clinical practice. PMID- 29795340 TI - Author Correction: The axolotl genome and the evolution of key tissue formation regulators. AB - In the originally published version of this Article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'D/D' rather than 'd/d' in Fig. 1a and the accompanying legend, the main text and the Methods section. The original Article has been corrected online. PMID- 29795341 TI - Author Correction: A series of energetic metal pentazolate hydrates. AB - In this Letter, under Methods section '[Na(H2O)(N5)]?2H2O (2)', the description "the intermediate product arylpentazole (5.000 g, 26.18 mmol)" should have read "the intermediate product sodium salt of arylpentazole (5.000 g, 21.64 mmol)". In the legend of Fig. 3, we add that "All temperature points in the stability study were onset temperatures." to avoid misunderstanding. These corrections have been made online. PMID- 29795342 TI - Structural basis of ubiquitin modification by the Legionella effector SdeA. AB - Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process. PMID- 29795343 TI - Late-surviving stem mammal links the lowermost Cretaceous of North America and Gondwana. AB - Haramiyida was a successful clade of mammaliaforms, spanning the Late Triassic period to at least the Late Jurassic period, but their fossils are scant outside Eurasia and Cretaceous records are controversial1-4. Here we report, to our knowledge, the first cranium of a large haramiyidan from the basal Cretaceous of North America. This cranium possesses an amalgam of stem mammaliaform plesiomorphies and crown mammalian apomorphies. Moreover, it shows dental traits that are diagnostic of isolated teeth of supposed multituberculate affinities from the Cretaceous of Morocco, which have been assigned to the enigmatic 'Hahnodontidae'. Exceptional preservation of this specimen also provides insights into the evolution of the ancestral mammalian brain. We demonstrate the haramiyidan affinities of Gondwanan hahnodontid teeth, removing them from multituberculates, and suggest that hahnodontid mammaliaforms had a much wider, possibly Pangaean distribution during the Jurassic-Cretaceous transition. PMID- 29795345 TI - Long-term effects of species loss on community properties across contrasting ecosystems. AB - Biodiversity loss can heavily affect the functioning of ecosystems, and improving our understanding of how ecosystems respond to biodiversity decline is one of the main challenges in ecology1-4. Several important aspects of the longer-term effects of biodiversity loss on ecosystems remain unresolved, including how these effects depend on environmental context5-7. Here we analyse data from an across ecosystem biodiversity manipulation experiment that, to our knowledge, represents the world's longest-running experiment of this type. This experiment has been set up on 30 lake islands in Sweden that vary considerably in productivity and soil fertility owing to differences in fire history8,9. We tested the effects of environmental context on how plant species loss affected two fundamental community attributes-plant community biomass and temporal variability-over 20 years. In contrast to findings from artificially assembled communities10-12, we found that the effects of species loss on community biomass decreased over time; this decrease was strongest on the least productive and least fertile islands. Species loss generally also increased temporal variability, and these effects were greatest on the most productive and most fertile islands. Our findings highlight that the ecosystem-level consequences of biodiversity loss are not constant across ecosystems and that understanding and forecasting these consequences necessitates taking into account the overarching role of environmental context. PMID- 29795344 TI - Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche. AB - The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix1-3. Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells4-9, the composition and source of molecules that maintain the stem cell niche remain largely unknown. Here we show that adult muscle satellite (stem) cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, we identified NOTCH1/RBPJ-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, we show that Collagen V (COLV) produced by satellite cells is a critical component of the quiescent niche, as depletion of COLV by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of COLV with satellite cells is mediated by the Calcitonin receptor, for which COLV acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in COLV-null satellite cells. This study reveals a Notch-COLV-Calcitonin receptor signalling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion, and raises the possibility that similar reciprocal mechanisms act in diverse stem cell populations. PMID- 29795346 TI - Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector. AB - Ubiquitination is a post-translational modification that regulates many cellular processes in eukaryotes1-4. The conventional ubiquitination cascade culminates in a covalent linkage between the C terminus of ubiquitin (Ub) and a target protein, usually on a lysine side chain1,5. Recent studies of the Legionella pneumophila SidE family of effector proteins revealed a ubiquitination method in which a phosphoribosyl ubiquitin (PR-Ub) is conjugated to a serine residue on substrates via a phosphodiester bond6-8. Here we present the crystal structure of a fragment of the SidE family member SdeA that retains ubiquitination activity, and determine the mechanism of this unique post-translational modification. The structure reveals that the catalytic module contains two distinct functional units: a phosphodiesterase domain and a mono-ADP-ribosyltransferase domain. Biochemical analysis shows that the mono-ADP-ribosyltransferase domain-mediated conversion of Ub to ADP-ribosylated Ub (ADPR-Ub) and the phosphodiesterase domain mediated ligation of PR-Ub to substrates are two independent activities of SdeA. Furthermore, we present two crystal structures of a homologous phosphodiesterase domain from the SidE family member SdeD 9 in complexes with Ub and ADPR-Ub. The structures suggest a mechanism for how SdeA processes ADPR-Ub to PR-Ub and AMP, and conjugates PR-Ub to a serine residue in substrates. Our study establishes the molecular mechanism of phosphoribosyl-linked ubiquitination and will enable future studies of this unusual type of ubiquitination in eukaryotes. PMID- 29795347 TI - Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination. AB - Conventional ubiquitination regulates key cellular processes by catalysing the ATP-dependent formation of an isopeptide bond between ubiquitin (Ub) and primary amines in substrate proteins 1 . Recently, the SidE family of bacterial effector proteins (SdeA, SdeB, SdeC and SidE) from pathogenic Legionella pneumophila were shown to use NAD+ to mediate phosphoribosyl-linked ubiquitination of serine residues in host proteins2, 3. However, the molecular architecture of the catalytic platform that enables this complex multistep process remains unknown. Here we describe the structure of the catalytic core of SdeA, comprising mono-ADP ribosyltransferase (mART) and phosphodiesterase (PDE) domains, and shed light on the activity of two distinct catalytic sites for serine ubiquitination. The mART catalytic site is composed of an alpha-helical lobe (AHL) that, together with the mART core, creates a chamber for NAD+ binding and ADP-ribosylation of ubiquitin. The catalytic site in the PDE domain cleaves ADP-ribosylated ubiquitin to phosphoribosyl ubiquitin (PR-Ub) and mediates a two-step PR-Ub transfer reaction: first to a catalytic histidine 277 (forming a transient SdeA H277-PR-Ub intermediate) and subsequently to a serine residue in host proteins. Structural analysis revealed a substrate binding cleft in the PDE domain, juxtaposed with the catalytic site, that is essential for positioning serines for ubiquitination. Using degenerate substrate peptides and newly identified ubiquitination sites in RTN4B, we show that disordered polypeptides with hydrophobic residues surrounding the target serine residues are preferred substrates for SdeA ubiquitination. Infection studies with L. pneumophila expressing substrate-binding mutants of SdeA revealed that substrate ubiquitination, rather than modification of the cellular ubiquitin pool, determines the pathophysiological effect of SdeA during acute bacterial infection. PMID- 29795348 TI - Self-organization of a human organizer by combined Wnt and Nodal signalling. AB - In amniotes, the development of the primitive streak and its accompanying 'organizer' define the first stages of gastrulation. Although these structures have been characterized in detail in model organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers 1 . Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial-to-mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host. This fulfils the most stringent functional criteria for an organizer, and its discovery represents a milestone in human embryology. PMID- 29795349 TI - Cortical direction selectivity emerges at convergence of thalamic synapses. AB - Detecting the direction of motion of an object is essential for our representation of the visual environment. The visual cortex is one of the main stages in the mammalian nervous system in which the direction of motion may be computed de novo. Experiments and theories indicate that cortical neurons respond selectively to motion direction by combining inputs that provide information about distinct spatial locations with distinct time delays. Despite the importance of this spatiotemporal offset for direction selectivity, its origin and cellular mechanisms are not fully understood. We show that approximately 80 +/- 10 thalamic neurons, which respond with distinct time courses to stimuli in distinct locations, excite mouse visual cortical neurons during visual stimulation. The integration of thalamic inputs with the appropriate spatiotemporal offset provides cortical neurons with a primordial bias for direction selectivity. These data show how cortical neurons selectively combine the spatiotemporal response diversity of thalamic neurons to extract fundamental features of the visual world. PMID- 29795350 TI - Body-size shifts in aquatic and terrestrial urban communities. AB - Body size is intrinsically linked to metabolic rate and life-history traits, and is a crucial determinant of food webs and community dynamics1,2. The increased temperatures associated with the urban-heat-island effect result in increased metabolic costs and are expected to drive shifts to smaller body sizes 3 . Urban environments are, however, also characterized by substantial habitat fragmentation 4 , which favours mobile species. Here, using a replicated, spatially nested sampling design across ten animal taxonomic groups, we show that urban communities generally consist of smaller species. In addition, although we show urban warming for three habitat types and associated reduced community weighted mean body sizes for four taxa, three taxa display a shift to larger species along the urbanization gradients. Our results show that the general trend towards smaller-sized species is overruled by filtering for larger species when there is positive covariation between size and dispersal, a process that can mitigate the low connectivity of ecological resources in urban settings 5 . We thus demonstrate that the urban-heat-island effect and urban habitat fragmentation are associated with contrasting community-level shifts in body size that critically depend on the association between body size and dispersal. Because body size determines the structure and dynamics of ecological networks 1 , such shifts may affect urban ecosystem function. PMID- 29795353 TI - Addendum: Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols. PMID- 29795351 TI - Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. AB - De novo mutations in ADNP, which encodes activity-dependent neuroprotective protein (ADNP), have recently been found to underlie Helsmoortel-Van der Aa syndrome, a complex neurological developmental disorder that also affects several other organ functions 1 . ADNP is a putative transcription factor that is essential for embryonic development 2 . However, its precise roles in transcriptional regulation and development are not understood. Here we show that ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine 9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. Together, our results reveal that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression1,3,4. Notably, we found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome, and this could be rescued by aminoglycosides that suppress translation termination 5 . Therefore, patients might benefit from therapeutic agents that are being developed to promote ribosomal read-through of premature stop codons6,7. PMID- 29795352 TI - An increase in the 12C + 12C fusion rate from resonances at astrophysical energies. AB - Carbon burning powers scenarios that influence the fate of stars, such as the late evolutionary stages of massive stars 1 (exceeding eight solar masses) and superbursts from accreting neutron stars2,3. It proceeds through the 12C + 12C fusion reactions that produce an alpha particle and neon-20 or a proton and sodium-23-that is, 12C(12C, alpha)20Ne and 12C(12C, p)23Na-at temperatures greater than 0.4 * 109 kelvin, corresponding to astrophysical energies exceeding a megaelectronvolt, at which such nuclear reactions are more likely to occur in stars. The cross-sections 4 for those carbon fusion reactions (probabilities that are required to calculate the rate of the reactions) have hitherto not been measured at the Gamow peaks 4 below 2 megaelectronvolts because of exponential suppression arising from the Coulomb barrier. The reference rate 5 at temperatures below 1.2 * 109 kelvin relies on extrapolations that ignore the effects of possible low-lying resonances. Here we report the measurement of the 12C(12C, alpha0,1)20Ne and 12C(12C, p0,1)23Na reaction rates (where the subscripts 0 and 1 stand for the ground and first excited states of 20Ne and 23Na, respectively) at centre-of-mass energies from 2.7 to 0.8 megaelectronvolts using the Trojan Horse method6,7 and the deuteron in 14N. The cross-sections deduced exhibit several resonances that are responsible for very large increases of the reaction rate at relevant temperatures. In particular, around 5 * 108 kelvin, the reaction rate is boosted to more than 25 times larger than the reference value 5 . This finding may have implications such as lowering the temperatures and densities 8 required for the ignition of carbon burning in massive stars and decreasing the superburst ignition depth in accreting neutron stars to reconcile observations with theoretical models 3 . PMID- 29795355 TI - Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure. AB - Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-alpha, IL-6, and IL-1beta in the non-infarcted region four weeks after injection. Changes of the TNF-alpha, IL-6, and IL-1beta levels in the non infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation. PMID- 29795356 TI - Astragaloside IV ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPARgamma/NF-kappaB/NLRP3 inflammasome axis. AB - Major depressive disorder is a common but devastating mental disorder, and recent evidence shows that neuroinflammation may play a pivotal role in the etiology of depression. Astragaloside IV (AS-IV) is an active component purifed from Astragalus membranaceus (Fisch) Bge, which has shown anti-inflammatory, anti oxidative and anti-apoptotic effects. In this study, we explored whether AS-IV produced antidepressant effects via its inhibition of neuroinflammation in mouse models of depression. Depressive-like behaviors including decreased sucrose consumption, reduced locomotor activity and increased immobility time were induced in mice using repeated restraint stress (RRS). We found that administration of AS-IV (16, 32 and 64 mg.kg-1.d-1, ig) significantly attenuated RRS-induced depressive-like behaviors. Furthermore, AS-IV administration significantly reduced the levels of TNF-alpha and IL-1beta, increased PPARgamma expression and GSK3beta phosphorylation, decreased NF-kappaB phosphorylation, and reduced NOD-, LRR- and pyrin domain-containingprotein 3 (NLRP3) inflammasome and caspase-1 p20 generation in the hippocampus of the mice. LPS-induced depression like behaviors were induced by LPS injection (1 mg.kg-1.d-1, ip), which were ameliorated by administration of AS-IV (20, 40 mg.kg-1.d-1, ig). The results of the LPS-induced mouse model were in accordance with those acquired from the RRS induced mouse model: LPS injection significantly increased TNF-alpha and IL-1beta expression in the mouse hippocampus, which was reversed by administration of AS IV. Moreover, administration of AS-IV significantly increased PPARgamma expression and GSK3beta phosphorylation, and decreased NF-kappaB phosphorylation and NLRP3 inflammasome. These results suggest that AS-IV is a potential drug against depression, and its antidepressant effects are partially mediated by inhibition of neuroinflammation via the upregulation of PPARgamma expression. PMID- 29795354 TI - Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. AB - As with many pathogens, most dengue infections are subclinical and therefore unobserved 1 . Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements)2,3. We identify 1,149 infections (95% confidence interval, 1,135-1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of <=1:40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5-8.2) times more often than naive individuals compared to 0.0 times for individuals with titres >1:40 (95% confidence interval: 0.0-1.3). Plaque reduction neutralization test titres <=1:100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age. PMID- 29795357 TI - Pharmacological and functional comparisons of alpha6/alpha3beta2beta3-nAChRs and alpha4beta2-nAChRs heterologously expressed in the human epithelial SH-EP1 cell line. AB - Neuronal nicotinic acetylcholine receptors containing alpha6 subunits (alpha6* nAChRs) show highly restricted distribution in midbrain neurons associated with pleasure, reward, and mood control, suggesting an important impact of alpha6* nAChRs in modulating mesolimbic functions. However, the function and pharmacology of alpha6*-nAChRs remain poorly understood because of the lack of selective agonists for alpha6*-nAChRs and the challenging heterologous expression of functional alpha6*-nAChRs in mammalian cell lines. In particular, the alpha6 subunit is commonly co-expressed with alpha4*-nAChRs in the midbrain, which masks alpha6*-nAChR (without alpha4) function and pharmacology. In this study, we systematically profiled the pharmacology and function of alpha6*-nAChRs and compared these properties with those of alpha4beta2 nAChRs expressed in the same cell line. Heterologously expressed human alpha6/alpha3 chimeric subunits (alpha6 N-terminal domain joined with alpha3 trans-membrane domains and intracellular loops) with beta2 and beta3 subunits in the human SH-EP1 cell line (alpha6* nAChRs) were used. Patch-clamp whole-cell recordings were performed to measure these receptor-mediated currents. Functionally, the heterologously expressed alpha6*-nAChRs exhibited excellent function and showed distinct nicotine-induced current responses, such as kinetics, inward rectification and recovery from desensitization, compared with alpha4beta2-nAChRs. Pharmacologically, alpha6* nAChR was highly sensitive to the alpha6 subunit-selective antagonist alpha conotoxin MII but had lower sensitivity to mecamylamine and dihydro-beta erythroidine. Nicotine and acetylcholine were found to be full agonists for alpha6*-nAChRs, whereas epibatidine and cytisine were determined to be partial agonists. Heterologously expressed alpha6*-nAChRs exhibited pharmacology and function distinct from those of alpha4beta2-nAChRs, suggesting that alpha6* nAChRs may mediate different cholinergic signals. Our alpha6*-nAChR expression system can be used as an excellent cell model for future investigations of alpha6*-nAChR function and pharmacology. PMID- 29795358 TI - Novel substituted pyrazolone derivatives as AMP-activated protein kinase activators to inhibit lipid synthesis and reduce lipid accumulation in ob/ob mice. AB - Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatic steatosis. NAFLD is closely linked to obesity, insulin resistance and dyslipidemia. AMP-activated protein kinase (AMPK) functions as an energy sensor and plays a central role in regulating lipid metabolism. In this study, we identified a series of novel pyrazolone AMPK activators using a homogeneous time resolved fluorescence assay (HTRF) based on the AMPKalpha2beta1gamma1 complex. Compound 29 (C29) is a candidate compound that directly activated the kinase domain of AMPK with an EC50 value of 2.1-0.2 MUmol/L and acted as a non-selective activator of AMPK complexes. Treatment of HepG2 cells with C29 (20, 40 MUmol/L) dose-dependently inhibited triglyceride accumulation. Chronic administration of C29 (10, 30 mg/kg every day, po, for 5 weeks) significantly improved lipid metabolism in both the liver and the plasma of ob/ob mice. These results demonstrate that the AMPK activators could be part of a novel treatment approach for NAFLD and associated metabolic disorders. PMID- 29795359 TI - Identification of small molecule inhibitors targeting the SMARCA2 bromodomain from a high-throughput screening assay. AB - SMARCA2 is a critical catalytic subunit of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes. Dysregulation of SMARCA2 is associated with several diseases, including some cancers. SMARCA2 is multi-domain protein containing a bromodomain (BRD) that specifically recognizes acetylated lysine residues in histone tails, thus playing an important role in chromatin remodeling. Many potent and specific inhibitors targeting other BRDs have recently been discovered and have been widely used for cancer treatments and biological research. However, hit discovery targeting SMARCA2-BRD is particularly lacking. To date, there is a paucity of reported high-throughput screening (HTS) assays targeting the SMARCA2-BRD interface. In this study, we developed an AlphaScreen HTS system for the discovery of SMARCA2-BRD inhibitors and optimized the physicochemical conditions including pH, salt concentrations and detergent levels. Through an established AlphaScreen-based high-throughput screening assay against an in-house compound library, DCSM06 was identified as a novel SMARCA2 BRD inhibitor with an IC50 value of 39.9+/-3.0 MUmol/L. Surface plasmon resonance demonstrated the binding between SMARCA2-BRD and DCSM06 (Kd=38.6 MUmol/L). A similarity-based analog search led to identification of DCSM06-05 with an IC50 value of 9.0+/-1.4 MUmol/L. Molecular docking was performed to predict the binding mode of DCSM06-05 and to decipher the structural basis of the infiuence of chemical modifications on inhibitor potency. DCSM06-05 may be used as a starting point for further medicinal chemistry optimization and could function as a chemical tool for SMARCA2-related functional studies. PMID- 29795360 TI - Plasma miR-451 with echocardiography serves as a diagnostic reference for pulmonary hypertension. AB - Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to identify dynamic miRNAs between PH and non-PH patients. The candidate miRNAs were verified using qRT-PCR in a mouse model of PH, which was induced by monocrotaline (MCT) injection. We observed that miR-21, miR-126, miR-145, miR-191 and miR-150 had no differences between control mice and MCT-treated mice; but plasma miR-451 was significantly decreased in the 2wk-MCT group, with no further decrease in the 4wk-MCT group. Plasma miR-451 was also markedly decreased in PH patients, whereas miR-21, miR-126, miR-150 and miR-320 did not show differences between 53 PH patients and 54 non-PH patients. Receiver operating characteristic curves (ROCs) were constructed from the patient data to assess the clinical diagnostic values of circulating miR-451 and Doppler echocardiography (D-ECHO). The areas under the curve (AUCs) of ROCs for miR-451 and D-ECHO were 0.710 and 0.766, respectively. Combination of miR-451 and D-ECHO with AUC of 0.825 was superior to the use of either miR-451 or D-ECHO alone for PH diagnosis. In conclusion, plasma miR-451 has a moderate diagnostic value in PH comparable to that of D-ECHO, and the combination of miR-451 with D-ECHO has better diagnostic value than either method alone, which may have implications for PH diagnosis. PMID- 29795362 TI - Prolonged DADLE exposure epigenetically promotes Bcl-2 expression and elicits neuroprotection in primary rat cortical neurons via the PI3K/Akt/NF-kappaB pathway. AB - Both in vivo and in vitro studies have shown the beneficial effects of the delta opioid receptor (DOR) on neurodegeneration in hypoxia/ischemia. We previously reported that DOR stimulation with [(D-Ala2, D-Leu5) enkephalin] (DADLE), a potent DOR agonist, for both a short (minutes) and long (days) time has notable protective effects against sodium azide (NaN3)-induced cell injury in primary cultured rat cortical neurons. We further demonstrated that short-term DADLE stimulation increased neuronal survival through the PKC-mitochondrial ERK pathway. However, the mechanisms underlying long-term neuroprotection by DADLE remain unclear. Here, we showed that DOR stimulation with DADLE (0.1 MUmol/L) for 2 d selectively activates the PI3K/Akt/NF-kappaB pathway in NaN3-treated neurons; this activation increased Bcl-2 expression, attenuated Cyto c release and promoted neuronal survival. Further investigation revealed that sustained DADLE stimulation increased Bcl-2 expression by enhancing NF-kappaB binding to the Bcl 2 promoter and upregulating the histone acetylation levels of the Bcl-2 promoter. Our results demonstrate that prolonged DADLE exposure epigenetically promotes Bcl 2 expression and elicits neuroprotective effects in the NaN3 model via the PI3K/Akt/NF-kappaB pathway. PMID- 29795363 TI - Borderline personality disorder. AB - Caretakers are often intimidated or alienated by patients with borderline personality disorder (BPD), compounding the clinical challenges posed by the severe morbidity, high social costs and substantial prevalence of this disorder in many health-care settings. BPD is found in ~1.7% of the general population but in 15-28% of patients in psychiatric clinics or hospitals and in a large proportion of individuals seeking help for psychological problems in general health facilities. BPD is characterized by extreme sensitivity to perceived interpersonal slights, an unstable sense of self, intense and volatile emotionality and impulsive behaviours that are often self-destructive. Most patients gradually enter symptomatic remission, and their rate of remission can be accelerated by evidence-based psychosocial treatments. Although self-harming behaviours and proneness to crisis can decrease over time, the natural course and otherwise effective treatments of BPD usually leave many patients with persistent and severe social disabilities related to depression or self-harming behaviours. Thus, clinicians need to actively enquire about the central issues of interpersonal relations and unstable identity. Failure to correctly diagnose patients with BPD leads to misleading pharmacological interventions that rarely succeed. Whether the definition of BPD should change is under debate that is linked to not fully knowing the nature of this disorder. PMID- 29795361 TI - Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-kappaB pathway. AB - Lower back pain (LBP) is the most common disease in orthopedic clinics world wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 MUg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-kappaB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF kappaB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP. PMID- 29795364 TI - AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment. AB - Early stage prostate cancers are dependent on androgens for their growth and survival and androgen withdrawal causes them to regress. Progressive prostate cancers eventually acquire androgen independence rendering anti-androgen therapy ineffective. However, the factors leading to this have not been adequately addressed. This study shows that AIRE finds differential expression in androgen dependent and -independent prostate cancer cells. AIRE expression is more in androgen-independent cells due to its regulation by transcription factor Elk-1. These enhanced levels of AIRE modulate the prostate tumor microenvironment by transcriptionally activating a malignancy gene IL-6 in androgen-independent cells. Additionally, AIRE prevents the cancer cells from anticancer drug-induced death and enhances their invasiveness. Moreover, AIRE by modulating the cytokine milieu skews the tumor-associated macrophage polarization towards M2 phenotype with increased CD206 and CD163 expression. Subcutaneous mouse model of prostate cancer revealed AIRE+/+ mice forming a palpable tumor and presents lymphadenopathy however, only a small benign tumor is observed in AIRE-/- mice and lymph nodes appear normal in size. In conclusion, our findings suggest AIRE as a probable factor in promoting prostate cancer progression. PMID- 29795365 TI - Financial incentive strategies for maintenance of weight loss: results from an internet-based randomized controlled trial. AB - BACKGROUND/OBJECTIVE: Financial incentives can improve initial weight loss; we examined whether financial incentives can improve weight loss maintenance. SUBJECTS/METHODS: Participants aged 30-80 years who lost at least 5 kg during the first 4-6 months in a nationally available commercial weight loss program were recruited via the internet into a three-arm randomized trial of two types of financial incentives versus active control during months 1-6 (Phase I) followed by passive monitoring during months 7-12 (Phase II). Interventions were daily self-weighing and text messaging feedback alone (control) or combined with a lottery-based incentive or a direct incentive. The primary outcome was weight change 6 months after initial weight loss. Secondary outcomes included weight change 12 months after initial weight loss (6 months after cessation of maintenance intervention), and self-reported physical activity and eating behaviors. RESULTS: Of 191 participants randomized, the mean age was 49.0 (SD = 10.5) years and weight loss prior to randomization was 11.4 (4.7) kg; 92% were women and 89% were White. Mean weight changes during the next 6 months (Phase I) were: lottery -3.0 (5.8) kg; direct -2.8 (5.8) kg; and control -1.4 (5.8) kg (all pairwise comparisons p > 0.1). Weight changes through the end of 12 months post weight loss (Phase II) were: lottery -1.8 (10.5) kg; direct -0.7 (10.7) kg; and control -0.3 (9.4) kg (all pairwise comparisons p > 0.1). The percentages of participants who maintained their weight loss (defined as gaining <=1.36 kg) were: lottery 79%, direct 76%, and control 67% at 6 months and lottery 66%, direct 62%, and control 59% at 12 months (all pairwise comparisons p > 0.1). At 6 and 12 months after initial weight loss, changes in self-reported physical activity or eating behaviors did not differ across arms. CONCLUSIONS: Compared with the active control of daily texting based on daily home weighing, lottery based and direct monetary incentives provided no additional benefit for weight loss maintenance. PMID- 29795366 TI - Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. AB - We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73-0.99], P = 0.04) and tended to be directly associated with insulin secretion (beta = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 * 10-6) and negatively with hsCRP concentrations at both sampling (r = - 0.22, P = 0.0001) and study follow-up (beta = - 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on beta-cell function. PMID- 29795367 TI - Ultra-processed food consumption and adiposity trajectories in a Brazilian cohort of adolescents: ELANA study. AB - BACKGROUND/OBJECTIVES: In Brazil, the increase in obesity rates has been accompanied by increased consumption of ultra-processed food (UPF). The objective of this paper was to evaluate body mass index (BMI) and body fat percentage (%BF) trajectories in adolescents over a 3-year follow-up according to the frequency of UPF consumption. SUBJECTS/METHODS: Data of three consecutive years (2010, 2011, and 2012) were obtained from the Adolescent Nutritional Assessment Longitudinal Study (ELANA) that aimed to assess changes in anthropometric indicators of nutritional status, and 1035 adolescents enrolled in the 1st year of high school from six schools (four private and two public) in the metropolitan area of Rio de Janeiro, Brazil were included. At three follow-ups, they had their weights and heights measured. Body composition was measured at the first and second follow ups. Mixed linear regression models were used to estimate BMI and %BF trajectories based on quartiles of UPF intake, adjusting for type of school, sex, physical activity, and underreporting. RESULTS: Compared to their counterparts in the 1st quartile, adolescents in the 4th quartile of UPF consumption had a lower daily intake of fruits, cooked vegetables, and raw vegetables and a higher intake of total sugar and physical activity levels (p < 0.001). There was an inverse association between UPF consumption and BMI both at baseline and at follow-up. Values for %BF followed the same trend. Adolescents in the 4th quartile had the greatest level of physical activity and lowest total energy intake. CONCLUSION: This study confirmed that greater intake of UPF is a marker of an unhealthy diet, but did not support the hypothesis of a high rate of change in BMI associated with greater UPF consumption, even after adjusting for physical activity. PMID- 29795368 TI - Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study. AB - BACKGROUND: Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS: In a double blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS: Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 +/- 1.0 and 2.5 +/- 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS: In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment. PMID- 29795369 TI - NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest. AB - Notch dysregulation has been implicated in numerous tumors, including triple negative breast cancer (TNBC), which is the breast cancer subtype with the worst clinical outcome. However, the importance of individual receptors in TNBC and their specific mechanism of action remain to be elucidated, even if recent findings suggested a specific role of activated-Notch3 in a subset of TNBCs. Epidermal growth factor receptor (EGFR) is overexpressed in TNBCs but the use of anti-EGFR agents (including tyrosine kinase inhibitors, TKIs) has not been approved for the treatment of these patients, as clinical trials have shown disappointing results. Resistance to EGFR blockers is commonly reported. Here we show that Notch3-specific inhibition increases TNBC sensitivity to the TKI gefitinib in TNBC-resistant cells. Mechanistically, we demonstrate that Notch3 is able to regulate the activated EGFR membrane localization into lipid rafts microdomains, as Notch3 inhibition, such as rafts depletion, induces the EGFR internalization and its intracellular arrest, without involving receptor degradation. Interestingly, these events are associated with the EGFR tyrosine dephosphorylation at Y1173 residue (but not at Y1068) by the protein tyrosine phosphatase H1 (PTPH1), thus suggesting its possible involvement in the observed Notch3-dependent TNBC sensitivity response to gefitinib. Consistent with this notion, a nuclear localization defect of phospho-EGFR is observed after combined blockade of EGFR and Notch3, which results in a decreased TNBC cell survival. Notably, we observed a significant correlation between EGFR and NOTCH3 expression levels by in silico gene expression and immunohistochemical analysis of human TNBC primary samples. Our findings strongly suggest that combined therapies of TKI-gefitinib with Notch3-specific suppression may be exploited as a drug combination advantage in TNBC treatment. PMID- 29795370 TI - HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal dendritic cells and induction of intestinal cytotoxic T lymphocytes and IgA. AB - Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+ cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA specific CD8+ CTLs were not induced by oral administration of the CT active (CTA) or CT binding (CTB) subunit as an adjuvant and CD11c+ DCs were involved in cross priming of intestinal CTLs. CD8+CD103+CD11c+CD11b-DCs and DCIR2+CD103+CD11c+CD11b+ DCs were distributed in the intestinal lamina propria and mesenteric lymph nodes, both DC subsets expressed DEC-205, and the expression of co-stimulatory molecules such as CD80 and CD86 was enhanced in both DC subsets after oral administration of intact CT but not the CTA or CTB subunit. Intestinal DCs activated by the oral administration of OVA plus CT cross-presented OVA antigens and DCs that captured OVA antigen through DEC-205, but not DCIR2, could cross-present antigen. We found that oral administration of intact CT, but not the CTA or CTB subunit, enhanced cell death, cytoplasmic expression of high mobility group box 1 protein (HMGB1) in epithelial cell adhesion molecule (EpCAM)+CD45- intestinal epithelial cells (IECs), and HMGB1 levels in fecal extracts. HMGB1 dose-dependently enhanced the expression of CD80 and CD86 on DCs in vitro, and intravenous or oral administration of glycyrrhizin, an HMGB1 inhibitor, significantly suppressed activation of mucosal DCs and induction of intestinal OVA-specific CTLs and IgA by oral CT administration. These results showed that oral administration of intact CT triggers epithelial cell death in the gut and the release of HMGB1 from damaged IECs, and that the released HMGB1 may mediate activation of mucosal DCs and induction of CTLs and IgA in the intestine. PMID- 29795371 TI - Correction to: Phenytoin inhibits necroptosis. AB - The name of the one of the authors was misspelt. The author's surname is Rodriguez, not Rodriquez as originally published. This has been corrected in both the PDF and HTML versions of the Article. PMID- 29795372 TI - FAM188B enhances cell survival via interaction with USP7. AB - We have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, siFAM188B treatment induced the upregulation and activation of p53, and consequently increased p53-regulated pro-apoptotic proteins, PUMA and BAX. Proteomic analysis of FAM188B immunocomplexes revealed p53 and USP7 as putative FAM188B-interacting proteins. Deletion of the putative USP7-binding motif in FAM188B reduced complex formation of FAM188B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorage-independent growth in vitro. In addition, FAM188B knockdown by siRNA reduced tumor growth in xenografted mice, with an increase in p53 proteins. Taken together, our data suggest that FAM188B is a putative oncogene that functions via interaction with USP7. Therefore, control of FAM188B could be a possible target to inhibit tumor growth. PMID- 29795374 TI - Author Correction: Time-dependent memory transformation along the hippocampal anterior-posterior axis. AB - In the originally published version of this Article, the rightmost graph in Fig. 2c was inadvertently replaced with a duplicate of the central panel. This has now been corrected in both the PDF and HTML versions of the Article. PMID- 29795373 TI - Gamma synuclein is a novel Twist1 target that promotes TGF-beta-induced cancer cell migration and invasion. AB - Transforming growth factor beta (TGF-beta) is critical for embryonic development, adult tissue homeostasis, and tumor progression. TGF-beta suppresses tumors at early stage, but promotes metastasis at later stage through oncogenes such as Twist1. Gamma-synuclein (SNCG) is overexpressed in a variety of invasive and metastatic cancer. Here, we show that TGF-beta induces SNCG expression by Smad Twist1 axis, thus promoting TGF-beta- and Twist1-induced cancer cell migration and invasion. We identify multiple Twist1-binding sites (E-boxes) in SNCG promoter. Chromatin immunoprecipitation and luciferase assays confirm the binding of Twist1 to the E-boxes of SNCG promoter sequence (-129/-1026 bp). Importantly, the Twist1-binding site close to the transcription initiation site is critical for the upregulation of SNCG expression by TGF-beta and Twist1. Mutations of Twist1 motif on the SNCG promoter constructs markedly reduces the promoter activity. We further show that TGF-beta induces Twist1 expression through Smad thereby enhancing the binding of Twist1 to SNCG promoter, upregulating SNCG promoter activity and increasing SNCG expression. SNCG knockdown abrogates TGF beta- or Twist1-induced cancer cell migration and invasion. Finally, SNCG knockdown inhibits the promotion of cancer metastasis by Twist1. Together, our data demonstrate that SNCG is a novel target of TGF-beta-Smad-Twist1 axis and a mediator of Twist1-induced cancer metastasis. PMID- 29795376 TI - HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano 3-oxo-1,9-dien glycyrrhetinic acid analogue. AB - Methyl 2-cyano-3,12-dioxo-18beta-olean-1,9(11)-dien-30-oate (CDODO-Me, 10d) derived from glycyrrhetinic acid and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28 oic acid (CDDO-Me) derived from oleanoic acid are potent apoptosis inducers developed to clinical trials. Both compounds have high affinity for reduced glutathione (GSH), which needs to be overcome to improve their target selectivity. We generated a new 10d analogue methyl 2-cyano-3-oxo-18beta-olean 1,9(11), 12-trien-30-oate (COOTO, 10e), which retains high apoptosis inducing ability, while displaying decreased affinity for GSH, and explored the acting targets. We found that it induces Noxa level, reduces c-Flip level and causes Bax/Bak activation. Silencing of either Noxa or Bak significantly attenuated apoptosis induction of 10e. We linked these events due to targeting HDAC3/HDAC6 and Ku70 axis. 10e treatment reduced the levels of HDAC3 and HDAC6 with increased DNA damage/repair marker gamma-H2AX (gamma-H2AX) and acetylated Ku70. c-Flip dissociates from acetylated Ku70 undergoing degradation, while Bax dissociates from acetylated Ku70 undergoing activation. Silencing of either HDAC3 or HDAC6 enhanced 10e-induced apoptosis. We reveal a new action cascade of this category of compounds that involves targeting of HADC3/6 proteins and Ku70 acetylation. PMID- 29795375 TI - In situ edge engineering in two-dimensional transition metal dichalcogenides. AB - Exerting synthetic control over the edge structure and chemistry of two dimensional (2D) materials is of critical importance to direct the magnetic, optical, electrical, and catalytic properties for specific applications. Here, we directly image the edge evolution of pores in Mo1-xW x Se2 monolayers via atomic resolution in situ scanning transmission electron microscopy (STEM) and demonstrate that these edges can be structurally transformed to theoretically predicted metastable atomic configurations by thermal and chemical driving forces. Density functional theory calculations and ab initio molecular dynamics simulations explain the observed thermally induced structural evolution and exceptional stability of the four most commonly observed edges based on changing chemical potential during thermal annealing. The coupling of modeling and in situ STEM imaging in changing chemical environments demonstrated here provides a pathway for the predictive and controlled atomic scale manipulation of matter for the directed synthesis of edge configurations in Mo1-x W x Se2 to achieve desired functionality. PMID- 29795377 TI - An anti-EGFR * cotinine bispecific antibody complexed with cotinine-conjugated duocarmycin inhibits growth of EGFR-positive cancer cells with KRAS mutations. AB - Antibody-drug conjugates (ADCs) can selectively deliver cytotoxic agents to tumor cells and are frequently more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor-associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic. We prepared an anti-epidermal growth factor receptor (EGFR) * cotinine bispecific antibody and mixed it with an equimolar amount of cotinine-conjugated duocarmycin to form the ADC. This ADC showed significant in vitro and in vivo antitumor activity against EGFR-positive, cetuximab-refractory lung adenocarcinoma cells with KRAS mutations. PMID- 29795380 TI - Correction to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice. AB - Correction to: NPG Asia Materials (2018) https://doi.org/10.1038/s41427-018-0014 9 published online on 16 April 2018. PMID- 29795378 TI - Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1beta-induced autophagy. AB - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily "ancient", and three "modern". The MTBC strains belonging to "modern" lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1beta, IL 6, and TNF-alpha) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL 1beta, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1beta-induced autophagy is not disadvantageous for the survival of modern Mtb strains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages. PMID- 29795379 TI - HBx-induced S100A9 in NF-kappaB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells. AB - Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) infection. Myeloid-specific S100 proteins (S100s), namely, S100A8, S100A9 and S100A12, have been recently recognized as newly discovered damage-associated molecular patterns (DAMPs) that are correlated with progression in pathogen of infectious diseases. However, whether S100s are regulated by HBV and involved in HBV-related hepatocarcinogenesis are still unclear. Here, we found that all expression levels of myeloid-specific S100s (S100A8, S100A9 and S10012) were elevated in serum and tissue samples from HCC patients. Expression of S100A9 but not S100A8 and S10012 were also higher in blood serum and tissue samples from HBV positive HCC patients than that in HBV-negative HCC patients. High levels of intracellular and extracellular S100A9 were also confirmed in HepG2 cells expressing 1.3-fold HBV genome or HBV-encoded X protein (HBx) as well as in a stable HBV-producing cell line HepG2.2.15. HBx was shown to facilitate translocation of NF-kappaB from the cytoplasm to the nucleus, and NF-kappaB bound to the promoter of S100A9 to enhance its transcription. Silencing S100A9 expression partially blocked HBx-induced growth and metastasis of HepG2 cells both in vitro and in vivo. Further, serum S100A9 levels were found to correlate with TNM stage, extrahepatic metastasis status and HBV DNA load in HBV-related HCC and also had a better diagnostic value for identifying extrahepatic metastasis. Our these data demonstrate that S100A9 plays a pivotal role in HBx induced growth and metastasis of HCC and may serve as a potential diagnostic marker for extrahepatic metastasis. PMID- 29795381 TI - REGgamma deficiency suppresses tumor progression via stabilizing CK1epsilon in renal cell carcinoma. AB - Renal cell carcinoma (RCC) is the most common malignant disease of kidney in adults. The proteasome activator REGgamma was previously reported to promote the degradation of multiple important regulatory proteins and involved in the progression and development of numerous human cancers. Here, we first reported that REGgamma was upregulated in RCC and its upregulation was correlated with a poor prognosis in RCC patients. REGgamma depletion obviously suppressed RCC cells proliferation in vitro and in vivo. Notably, casein kinase 1epsilon (CK1epsilon) was identified as a novel target of REGgamma and knockdown of CK1epsilon effectively abolished the effect of REGgamma depletion on RCC cells growth. Importantly, we also observed that REGgamma depletion activated Hippo signaling pathway via stabilizing CK1epsilon in RCC, indicating the cross-talk between REGgamma/CK1epsilon axis and Hippo pathway during RCC development. In conclusion, our findings suggested that REGgamma played a pivotal role in the development of RCC and maybe helpful to identify new therapeutic strategies in the treatment of RCC. PMID- 29795382 TI - Dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia. AB - Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. We report exome sequencing of 64 matched samples collected from patients at initial diagnosis, during remission, and following relapse after historical combined RA-chemotherapy treatments. A first subgroup presents a high incidence of additional oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that these relapses derive from ancestral pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy. PMID- 29795384 TI - Soft Coulomb gap and asymmetric scaling towards metal-insulator quantum criticality in multilayer MoS2. AB - Quantum localization-delocalization of carriers are well described by either carrier-carrier interaction or disorder. When both effects come into play, however, a comprehensive understanding is not well established mainly due to complexity and sparse experimental data. Recently developed two-dimensional layered materials are ideal in describing such mesoscopic critical phenomena as they have both strong interactions and disorder. The transport in the insulating phase is well described by the soft Coulomb gap picture, which demonstrates the contribution of both interactions and disorder. Using this picture, we demonstrate the critical power law behavior of the localization length, supporting quantum criticality. We observe asymmetric critical exponents around the metal-insulator transition through temperature scaling analysis, which originates from poor screening in insulating regime and conversely strong screening in metallic regime due to free carriers. The effect of asymmetric scaling behavior is weakened in monolayer MoS2 due to a dominating disorder. PMID- 29795383 TI - An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging. AB - Electrical interactions between bacteria and the environment are delicate and essential. In this study, an external electrical current is applied to capacitive titania nanotubes doped with carbon (TNT-C) to evaluate the effects on bacteria killing and the underlying mechanism is investigated. When TNT-C is charged, post charging antibacterial effects proportional to the capacitance are observed. This capacitance-based antibacterial system works well with both direct and alternating current (DC, AC) and the higher discharging capacity in the positive DC (DC+) group leads to better antibacterial performance. Extracellular electron transfer observed during early contact contributes to the surface-dependent post charging antibacterial process. Physiologically, the electrical interaction deforms the bacteria morphology and elevates the intracellular reactive oxygen species level without impairing the growth of osteoblasts. Our finding spurs the design of light-independent antibacterial materials and provides insights into the use of electricity to modify biomaterials to complement other bacteria killing measures such as light irradiation. PMID- 29795385 TI - Evaluation of minimal residual disease using next-generation flow cytometry in patients with AL amyloidosis. PMID- 29795386 TI - Myelodysplastic syndromes current treatment algorithm 2018. AB - Myelodysplastic syndromes (MDS) include a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and a risk of clonal evolution and progression to acute myeloid leukemia (AML). Because outcomes for patients with MDS are heterogeneous, individual risk stratification using tools such as the revised International Prognostic Scoring System (IPSS-R) is important in managing patients-including selecting candidates for allogeneic hematopoietic stem cell transplantation (ASCT), the only potentially curative therapy for MDS. The IPSS-R can be supplemented by molecular genetic testing, since certain gene mutations such as TP53 influence risk independent of established clinicopathological variables. For lower risk patients with symptomatic anemia, treatment with erythropoiesis stimulating agents (ESAs) or lenalidomide (especially for those with deletion of chromosome 5q) can ameliorate symptoms. Some lower risk patients may be candidates for immunosuppressive therapy, thrombopoiesis-stimulating agents, or a DNA hypomethylating agent (HMA; azacitidine or decitabine). Among higher risk patients, transplant candidates should undergo ASCT as soon as possible, with HMAs useful as a bridge to transplant. Non-transplant candidates should initiate HMA therapy and continue if tolerated until disease progression. Supportive care with transfusions and antimicrobial drugs as needed remains important in all groups. PMID- 29795388 TI - Left gastric vein-based noninvasive test for esophageal varices: a same-day comparison of portal hemodynamic assessment with endoscopic appearance. AB - OBJECTIVE: To examine the effect of hemodynamic assessment of the left gastric vein (LGV) as a noninvasive test to diagnose esophageal varices (EV) in cirrhosis patients. METHODS: This cross-sectional study consisted of 229 cirrhosis patients (62.7 +/- 11.8 years; Child-Pugh score 5-14). One hundred fifty-four patients had EV (67.2%; small, 53; medium, 71; large, 30). All patients underwent a blood test and Doppler ultrasound followed by upper gastrointestinal endoscopy on the same day. The diagnostic ability for EV was compared between LGV-related findings and the platelet count/spleen diameter ratio (Plt/Spl). RESULTS: The detectability of the LGV was higher in patients with EV (129/144, 89.6%) than in those without (35/75, 46.7%; p < 0.0001), and was higher in those with large EV (30/30, 100%) than in those without (134/199, 67.3%; p = 0.0002). The positive detection of the LGV showed 100% sensitivity and negative predictive value (NPV) to identify large EV in the whole cohort and compensated group (n = 127). The best cutoff value in the LGV diameter was 5.35 mm to identify large EV, showing 0.753 area under the receiver operating characteristic curve (AUROC) with 90% sensitivity and 96.5% NPV. The Plt/Spl showed 62.1% sensitivity and 87.1% NPV, and the best cutoff value was 442.9 to identify large EV with 0.658 AUROC, which was comparable to LGV-based assessment (p = 0.162). CONCLUSIONS: This same-day comparison study demonstrated the value of LGV-based noninvasive test to identify large EV with high sensitivity and NPV in cirrhosis patients at a lower cost. PMID- 29795387 TI - OGG1-initiated base excision repair exacerbates oxidative stress-induced parthanatos. AB - Oxidative stress-induced DNA damage has been well acknowledged as a major cause leading to cell death, which is etiologically linked to ischemic injury and degenerative alterations. The most common oxidation product of DNA is base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), which is repaired by 8-oxoG glycosylase1 (OGG1)-initiated baseexcision repair (BER) pathway (OGG1-BER); however, the role of OGG1-BER in oxidative stress-induced cell death is poorly investigated. DNA strand breaks and apurinic/apyrimidinic (AP) sites are effective substrates to activate DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP1). Overactivation of PARP1 is associated with apoptosis-inducing factor (AIF)-mediated and caspase independent cell death (parthanatos). We hypothesized that after an excessive oxidative insult, OGG1-BER-generated strand breaks result in hyperactivation of PARP1 and consequently cell death. To test, wild type, knockout, siRNA-depleted MEFs and neuroblastoma cells, or those expressing repair-deficient OGG1 mutants were oxidatively stressed and the role of OGG1 was examined. Results showed that OGG1-BER further increases the levels of ROS-induced DNA damage by generating repair intermediates, leading to PARP1 overactivation and cell death. Cells lacking or expressing repair-deficient OGG1 showed lower levels of DNA strand lesions, PARP1 activation, and nuclear translocation of apoptosis-inducing factor, resulting in the increased resistance to ROS-induced parthanatos. These results suggested that OGG1 guards genome integrity through either lesion repair or elimination of cells with malignant potential, to maintain the homeostasis of the host, which might depend on the magnitude of guanine oxidation. PMID- 29795389 TI - Generation of ultrahigh field by micro-bubble implosion. AB - Breaking the 100-MeV barrier for proton acceleration will help elucidate fundamental physics and advance practical applications from inertial confinement fusion to tumour therapy. Herein we propose a novel concept of bubble implosions. A bubble implosion combines micro-bubbles and ultraintense laser pulses of 1020 1022 W cm-2 to generate ultrahigh fields and relativistic protons. The bubble wall protons undergo volumetric acceleration toward the centre due to the spherically symmetric Coulomb force and the innermost protons accumulate at the centre with a density comparable to the interior of a white dwarf. Then an unprecedentedly high electric field is formed, which produces an energetic proton flash. Three-dimensional particle simulations confirm the robustness of Coulomb imploded bubbles, which behave as nano-pulsars with repeated implosions and explosions to emit protons. Current technologies should be sufficient to experimentally verify concept of bubble implosions. PMID- 29795390 TI - Characterization of a newly isolated phage infecting pathogenic Escherichia coli and analysis of its mosaic structural genes. AB - The outbreak of multidrug-resistant pathogenic bacteria made the discovery of novel control strategies necessary. Phages have regained attention for their specific lytic activity against pathogenic bacterium. A newly isolated phage infecting the clinical Escherichia coli isolates, including several multidrug resistant strains, was isolated, and this phage showed high control effects against the tested pathogenic E. coli strains. Host range analysis revealed that although the phage exhibited broad lytic spectrum against the tested E. coli strains, it could not lyse strains from the other species. Comparative genomic analysis showed that phages had undergone at least three genome recombination events during the evolutionary process at the position of the three phage tail genes, which was reported to be associated with the host range determination of the phage. The recombinant tail proteins contained functional domains that were highly similar with genes of the Salmonella phage and genes of Pseudomonas and Neisseria. The findings of this study not only provide resources for developing phage therapy against E. coli, but also showed the highly variable genome structure of the phage. PMID- 29795391 TI - Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors. AB - Many hemorheologic Traditional Chinese Medicines (TCMs) that are widely-used clinically lack molecular mechanisms of action. We hypothesized that some of the active components of hemorheologic TCMs may function through targeting prothrombotic P2Y1 and/or P2Y12 receptors. The interactions between 253 antithrombotic compounds from TCM and these two G protein-coupled P2Y receptors were evaluated using virtual screening. Eleven highly ranked hits were further tested in radioligand binding and functional assays. Among these compounds, salvianolic acid A and C antagonized the activity of both P2Y1 and P2Y12 receptors in the low uM range, while salvianolic acid B antagonized the P2Y12 receptor. These three salvianolic acids are the major active components of the broadly-used hemorheologic TCM Danshen (Salvia militorrhiza), the antithrombotic molecular mechanisms of which were largely unknown. Thus, the combination of virtual screening and experimental validation identified potential mechanisms of action of multicomponent drugs that are already employed clinically. PMID- 29795393 TI - Author Correction: Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29795392 TI - Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling. AB - Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug distribution. We here present a proof-of concept study that uses mathematical modeling together with experimentation to address this challenge. Individual mice with 4T1 breast cancer were treated with either nanoparticle-delivered or free doxorubicin, with results demonstrating improved cancer kill efficacy of doxorubicin loaded nanoparticles in comparison to free doxorubicin. We then developed a mathematical theory to render model predictions from measured nanoparticle biodistribution, as determined using graphite furnace atomic absorption. Model analysis finds that treatment efficacy increased exponentially with increased nanoparticle accumulation within the tumor, emphasizing the significance of developing new ways to optimize the delivery efficiency of nanoparticles to the tumor microenvironment. PMID- 29795394 TI - Inflexible daily behaviour is associated with the ability to control an automatic reaction in autism spectrum disorder. AB - Inflexible behaviours in people with autism spectrum disorder (ASD) broadly obstruct social communication. Meanwhile, flexibility implicates cognitive control to resolve socially conflicting situations; however, it remains unclear how people with ASD behave in the face of these conflicts in this respect. We used the ultimatum game (UG) and the implicit-association test (IAT) to examine goal-directed/economic flexibility, both of which involve conflict and cognitive control. In addition, we used the Detail and Flexibility Questionnaire (DFlex) to measure inflexible everyday behaviour with diminished cognitive control and attention shifting. We observed the decreased flexibility in participants with ASD (DFlex and IAT); further, their IAT scores positively correlated with DFlex. However, in the UG, contrary to our prediction, participants with ASD accepted unfair offers more frequently than TD. These results suggest that assessing the automatic/attention processing level with the IAT could be a useful approach to study behavioural flexibility among ASD compared with the UG, which might comprise multiple response strategies besides economic rationality. Overall, the severity of inflexible daily behaviours in people with ASD may be associated with a reduced flexible attitude at an automatic level, altered attention processing and decreased cognitive control. PMID- 29795395 TI - A novel SNP in the 5' regulatory region of organic anion transporter 1 is associated with chronic kidney disease. AB - We aimed to analyze the associations of single nucleotide polymorphisms (SNP) in the 5' regulatory region of the human organic anion transporter 1 (OAT1) gene with chronic kidney disease (CKD). A case-control study including age- and sex matched groups of normal subjects and patients with CKD (n = 162 each) was designed. Direct sequencing of the 5' regulatory region (+88 to -1196 region) showed that patients with CKD had a higher frequency of the -475 SNP (T > T/G) than normal subjects (14/162 vs. 2/162). The luciferase activity assay results indicated that the -475G SNP had a higher promoter efficiency than the -475T SNP. Chromatin immunoprecipitation (ChIP) and LC/MS/MS analyses showed that the -475G SNP up-regulated 26 proteins and down-regulated 74 proteins. The Southwestern blot assay results revealed that the -475G SNP decreased the binding of Hepatoma derived growth factor (HDGF), a transcription repressor, compared to the -475T SNP. Overexpression of HDGF significantly down-regulated OAT1 in renal tubular cells. Moreover, a zebrafish animal model showed that HDGF-knockdown zebrafish embryos had higher rates of kidney malformation than wild-type controls [18/78 (23.1%) vs. 1/30 (3.3%)]. In conclusion, our results suggest that an OAT1 SNP might be clinically associated with CKD. Renal tubular cells with the -475 SNP had increased OAT1 expression, which resulted in increased transportation of organic anion toxins into cells. Cellular accumulation of organic anion toxins caused cytotoxicity and resulted in CKD. PMID- 29795398 TI - Tau seeding starts early in the entorhinal cortex. PMID- 29795396 TI - Toxicity and Transcriptome Sequencing (RNA-seq) Analyses of Adult Zebrafish in Response to Exposure Carboxymethyl Cellulose Stabilized Iron Sulfide Nanoparticles. AB - Increasing utilization of stabilized iron sulfides (FeS) nanoparticles implies an elevated release of the materials into the environment. To understand potential impacts and underlying mechanisms of nanoparticle-induced stress, we used the transcriptome sequencing (RNA-seq) technique to characterize the transcriptomes from adult zebrafish exposed to 10 mg/L carboxymethyl cellulose (CMC) stabilized FeS nanoparticles for 96 h, demonstrating striking differences in the gene expression profiles in liver. The exposure caused significant expression alterations in genes related to immune and inflammatory responses, detoxification, oxidative stress and DNA damage/repair. The complement and coagulation cascades Kyoto encyclopedia of genes and genomes (KEGG) pathway was found significantly up-regulated under nanoparticle exposure. The quantitative real-time polymerase chain reaction using twelve genes confirmed the RNA-seq results. We identified several candidate genes commonly regulated in liver, which may serve as gene indicators when exposed to the nanoparticles. Hepatic inflammation was further confirmed by histological observation of pyknotic nuclei, and vacuole formation upon exposure. Tissue accumulation tests showed a 2.2 times higher iron concentration in the fish tissue upon exposure. This study provides preliminary mechanistic insights into potential toxic effects of organic matter stabilized FeS nanoparticles, which will improve our understanding of the genotoxicity caused by stabilized nanoparticles. PMID- 29795399 TI - Selective neuronal loss could limit penumbral rescue after stroke. PMID- 29795397 TI - MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling. AB - MicroRNAs (miRs) contribute to biological robustness by buffering cellular processes from external perturbations. Here we report an unexpected link between DNA damage response and angiogenic signaling that is buffered by a miR. We demonstrate that genotoxic stress-induced miR-494 inhibits the DNA repair machinery by targeting the MRE11a-RAD50-NBN (MRN) complex. Gain- and loss-of function experiments show that miR-494 exacerbates DNA damage and drives endothelial senescence. Increase of miR-494 affects telomerase activity, activates p21, decreases pRb pathways, and diminishes angiogenic sprouting. Genetic and pharmacological disruption of the MRN pathway decreases VEGF signaling, phenocopies miR-494-induced senescence, and disrupts angiogenic sprouting. Vascular-targeted delivery of miR-494 decreases both growth factor induced and tumor angiogenesis in mouse models. Our work identifies a putative miR-facilitated mechanism by which endothelial cells can be insulated against VEGF signaling to facilitate the onset of senescence and highlight the potential of targeting DNA repair to disrupt pathological angiogenesis. PMID- 29795400 TI - Climate change is affecting mortality of weasels due to camouflage mismatch. AB - Direct phenological mismatch caused by climate change can occur in mammals that moult seasonally. Two colour morphs of the weasel Mustela nivalis (M. n.) occur sympatrically in Bialowieza Forest (NE Poland) and differ in their winter pelage colour: white in M. n. nivalis and brown in M. n. vulgaris. Due to their small body size, weasels are vulnerable to attacks by a range of different predators; thus cryptic coat colour may increase their winter survival. By analysing trapping data, we found that the share of white subspecies in the weasel population inhabiting Bialowieza Forest decreases with decreasing numbers of days with snow cover. This led us to hypothesise that selective predation pressure should favour one of the two phenotypes, according to the prevailing weather conditions in winter. A simple field experiment with weasel models (white and brown), exposed against different background colours, revealed that contrasting models faced significantly higher detection by predators. Our observations also confirmed earlier findings that the plasticity of moult in M. n. nivalis is very limited. This means that climate change will strongly influence the mortality of the nivalis-type due to prolonged camouflage mismatch, which will directly affect the abundance and geographical distribution of this subspecies. PMID- 29795401 TI - Validation of control genes and a standardised protocol for quantifying gene expression in the livers of C57BL/6 and ApoE-/- mice. AB - The liver plays a critical role in food and drug metabolism and detoxification and accordingly influences systemic body homeostasis in health and disease. While the C57BL/6 and ApoE-/- mouse models are widely used to study gene expression changes in liver disease and metabolism, currently there are no validated stably expressed endogenous genes in these models, neither is it known how gene expression varies within and across liver lobes. Here we show regional variations in the expression of Ywhaz, Gak, Gapdh, Hmbs and Act-beta endogenous genes across a liver lobe; Using homogeneous samples from the four liver lobes of 6 C57BL/6 mice we tested the stability of 12 endogenous genes and show that Act-beta and Eif2-alpha are the most stably expressed endogenous genes in all four lobes and demonstrate lobular differences in the expression of Abca1 cholesterol efflux gene. These results suggest that sampling from a specified homogeneous powdered liver lobe is paramount in enhancing data reliability and reproducibility. The stability of the 12 endogenous genes was further tested using homogeneous samples of left liver lobes from 20 ApoE-/- mice on standard or high polyphenol diets. Act-beta and Ywhaz are suitable endogenous genes for gene expression normalisation in this mouse model. PMID- 29795402 TI - Cross-shelf investigation of coral reef cryptic benthic organisms reveals diversity patterns of the hidden majority. AB - Coral reefs harbor diverse assemblages of organisms yet the majority of this diversity is hidden within the three dimensional structure of the reef and neglected using standard visual surveys. This study uses Autonomous Reef Monitoring Structures (ARMS) and amplicon sequencing methodologies, targeting mitochondrial cytochrome oxidase I and 18S rRNA genes, to investigate changes in the cryptic reef biodiversity. ARMS, deployed at 11 sites across a near- to off shore gradient in the Red Sea were dominated by Porifera (sessile fraction), Arthropoda and Annelida (mobile fractions). The two primer sets detected different taxa lists, but patterns in community composition and structure were similar. While the microhabitat of the ARMS deployment affected the community structure, a clear cross-shelf gradient was observed for all fractions investigated. The partitioning of beta-diversity revealed that replacement (i.e. the substitution of species) made the highest contribution with richness playing a smaller role. Hence, different reef habitats across the shelf are relevant to regional diversity, as they harbor different communities, a result with clear implications for the design of Marine Protected Areas. ARMS can be vital tools to assess biodiversity patterns in the generally neglected but species-rich cryptic benthos, providing invaluable information for the management and conservation of hard-bottomed habitats over local and global scales. PMID- 29795403 TI - Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. AB - Nicotine dependence and major depressive disorder (MDD) are highly comorbid, yet causal links between these prevalent disorders are unclear. One possible mechanism is that nicotine ameliorates MDD-related neurobiological dysfunction in specific networks. For instance, cortico-striatal circuitry is enhanced by nicotine, and such paths are disrupted in individuals with MDD. Specifically, MDD has been associated with reduced connectivity between the nucleus accumbens (NAc) and rostral anterior cingulate cortex (rACC) but enhanced connectivity between the dorsal striatum (DS) and dorsolateral prefrontal cortex (DLPFC). Determining whether nicotine normalizes these circuits in non-smokers with MDD may elucidate mechanisms underlying links between disorders. This was tested by administering placebo and a 2-mg dose of nicotine to unmedicated non-smokers with and without MDD prior to collecting resting-state functional magnetic imaging data using a cross-over design. On placebo, individuals with MDD showed significantly reduced NAc-rACC and a trend for enhanced DS-DLPFC functional connectivity relative to healthy controls. In MDD, acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. Nicotine's effects on NAc-rACC connectivity was influenced by anhedonia, consistent with the role of this network in reward and nicotine's ability to enhance reward deficiencies in MDD. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non smokers with MDD. Nicotine's influence on these circuitries highlights a possible mechanism whereby individuals with MDD are more vulnerable to develop nicotine dependence. Findings suggest that nicotinic agents may have therapeutic effects on disrupted cortico-striatal connectivity. PMID- 29795404 TI - Cerebral white matter sex dimorphism in alcoholism: a diffusion tensor imaging study. AB - Excessive alcohol consumption is associated with brain aberrations, including abnormalities in frontal and limbic brain regions. In a prior diffusion tensor magnetic resonance imaging (dMRI) study of neuronal circuitry connecting the frontal lobes and limbic system structures, we demonstrated decreases in white matter fractional anisotropy in abstinent alcoholic men. In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity and their association with alcoholism history. The dMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history. Sex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety. Our results suggest that sexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse. PMID- 29795406 TI - Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway. AB - Cancer chemotherapeutic agents such as doxorubicin are DNA damage inducers that also kill normal cells, making them highly toxic to cancer patients. To improve the efficacy and safety of chemotherapy, it is important to develop new chemotherapeutic agents that selectively kill cancer cells. Here we demonstrate that artemisitene (ATT), a natural derivative of the antimalarial drug artemisinin, selectively induces DNA double-stranded breaks (DSBs) and apoptosis in various human cancer cells by suppressing the expression of topoisomerases in human cancer cells. ATT effectively kills human cancer cells without apparent cytotoxicity on normal human cells or mouse liver and kidney. We discovered that c-Myc induces the expression of topoisomerases to prevent accumulation of DNA damage in human cancer cells. ATT selectively destabilizes c-Myc in human cancer cells by promoting the ubiquitination of c-Myc through the specific induction of the c-Myc E3 ligase NEDD4. Therefore, ATT represents a promising new chemotherapeutic drug candidate that can eliminate human cancer cells with minimized cytotoxic effects on normal cells. PMID- 29795405 TI - Myeloid-restricted ablation of Shp2 restrains melanoma growth by amplifying the reciprocal promotion of CXCL9 and IFN-gamma production in tumor microenvironment. AB - The Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp2) is generally considered to be an oncogene owing to its ability in enhancing the malignancy of multiple types of tumor cells; however, its role in modulating tumor immunity remains largely elusive. Here, we reported that myeloid-restricted ablation of Shp2 suppressed melanoma growth. Mechanistically, loss of Shp2 potentiates macrophage production of CXCL9 in response to IFN-gamma and tumor cell-derived cytokines, thereby facilitating the tumor infiltration of IFN-gamma producing T cells that could in turn support CXCL9 production within tumor microenvironment. Collectively, our findings highlight a causative role of myeloid Shp2 in dampening T cell-mediated antitumor immunity by restraining the macrophage/CXCL9-T cell/IFN-gamma feedback loop. Thus, targeting macrophage Shp2 may help to create a Th1-dominant tumor immune microenvironment. PMID- 29795409 TI - Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools. AB - The degree of agreement between four commercial pharmacogenetic-based decision support tools (DSTs) was examined in five outpatients with major depressive disorder and at least two previous antidepressant failures. Comparisons were made across seven pharmacokinetic (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UGT2B15) and seven pharmacodynamic (BDNF, COMT, HLA-A, HTR2A, HTR2C, OPRM1, and SLC6A4) genes that were included on >=2 of the four DST testing panels. Among these overlapping genes, genotype (33-100%) and predicted phenotype (20-100%) agreement varied substantially. Medication recommendation agreement was the greatest for mood stabilizers (84%), followed by antidepressants (56%), anxiolytics/hypnotics (56%), and antipsychotics (55%). Approximately one-quarter (26%) of all medication recommendations were jointly flagged by two or more DSTs as "actionable" but 19% of these recommendations provided conflicting advice (e.g., dosing) for the same medication.The level of disagreement in medication recommendations across the pharmacogenetic DSTs indicates that these tests cannot be assumed to be equivalent or interchangeable. Additional efforts to standardize genetic-based phenotyping and to develop medication guidelines are warranted. PMID- 29795408 TI - Integration of genetic and functional genomics data to uncover chemotherapeutic induced cytotoxicity. AB - Identifying genetic variants associated with chemotherapeutic induced toxicity is an important step towards personalized treatment of cancer patients. However, annotating and interpreting the associated genetic variants remains challenging because each associated variant is a surrogate for many other variants in the same region. The issue is further complicated when investigating patterns of associated variants with multiple drugs. In this study, we used biological knowledge to annotate and compare genetic variants associated with cellular sensitivity to mechanistically distinct chemotherapeutic drugs, including platinating agents (cisplatin, carboplatin), capecitabine, cytarabine, and paclitaxel. The most significantly associated SNPs from genome wide association studies of cellular sensitivity to each drug in lymphoblastoid cell lines derived from populations of European (CEU) and African (YRI) descent were analyzed for their enrichment in biological pathways and processes. We annotated genetic variants using higher-level biological annotations in efforts to group variants into more interpretable biological modules. Using the higher-level annotations, we observed distinct biological modules associated with cell line populations as well as classes of chemotherapeutic drugs. We also integrated genetic variants and gene expression variables to build predictive models for chemotherapeutic drug cytotoxicity and prioritized the network models based on the enrichment of DNA regulatory data. Several biological annotations, often encompassing different SNPs, were replicated in independent datasets. By using biological knowledge and DNA regulatory information, we propose a novel approach for jointly analyzing genetic variants associated with multiple chemotherapeutic drugs. PMID- 29795407 TI - Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. AB - Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10 7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous. PMID- 29795410 TI - MicroRNA21 and the various types of myeloid leukemia. AB - Myeloid leukemia (ML) is heterogeneous cancer classified by abnormal growth of myeloid cells due to genetic aberrations and mutations. It is generally categorized by clonal disorders of hematopoietic stem cells and differentiation. The molecular mechanism behind the myeloid malignancies is not yet known, but recent sequencing analysis reveals all the mutated factors. As we know that there is currently no compromise on therapy for such types of malignancies and at the present painful process like chemotherapy and radiation therapy are not effective for the treatment of ML, so there is an urgent need to develop a non-invasive biomarker for different types of ML. MicroRNAs (MiRNAs) is a small non-coding RNAs that have been involved in a wide range of biological function and it is the main cause of the manifestation of many diseases. Among the reported MiRNAs, MIR 21 is considered to be an important MiRNA, which is frequently elevated in many types of types of cancer, suggesting that it plays an important role in cancer progressions. So far, there is no paper that signifies the role of miR-21 in all types of ML and the number of studies on the different category of ML is sparse. Therefore, the main thrust of this paper is to provide an overview of the current clinical evidence and significance of miR-21 in ML. It was found that MiR-21 was found to be normally upregulated in all types of ML, however, we summarize the important research findings surrounding the role of miR-21 in different types of ML. PMID- 29795411 TI - Violent aggression predicted by multiple pre-adult environmental hits. AB - Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (<=1 vs. >=3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention. PMID- 29795412 TI - Effects of single amino acid deficiency on mRNA translation are markedly different for methionine versus leucine. AB - Although amino acids are known regulators of translation, the unique contributions of specific amino acids are not well understood. We compared effects of culturing HEK293T cells in medium lacking either leucine, methionine, histidine, or arginine on eIF2 and 4EBP1 phosphorylation and measures of mRNA translation. Methionine starvation caused the most drastic decrease in translation as assessed by polysome formation, ribosome profiling, and a measure of protein synthesis (puromycin-labeled polypeptides) but had no significant effect on eIF2 phosphorylation, 4EBP1 hyperphosphorylation or 4EBP1 binding to eIF4E. Leucine starvation suppressed polysome formation and was the only tested condition that caused a significant decrease in 4EBP1 phosphorylation or increase in 4EBP1 binding to eIF4E, but effects of leucine starvation were not replicated by overexpressing nonphosphorylatable 4EBP1. This suggests the binding of 4EBP1 to eIF4E may not by itself explain the suppression of mRNA translation under conditions of leucine starvation. Ribosome profiling suggested that leucine deprivation may primarily inhibit ribosome loading, whereas methionine deprivation may primarily impair start site recognition. These data underscore our lack of a full understanding of how mRNA translation is regulated and point to a unique regulatory role of methionine status on translation initiation that is not dependent upon eIF2 phosphorylation. PMID- 29795413 TI - Consequences of mutant TET2 on clonality and subclonal hierarchy. AB - Somatic mutations in TET2 are common in myelodysplastic syndromes (MDS), myeloproliferative, and overlap syndromes. TET2 mutant (TET2MT) clones are also found in asymptomatic elderly individuals, a condition referred to as clonal hematopoiesis of indeterminate potential (CHIP). In various entities of TET2MT neoplasia, we examined the phenotype in relation to the strata of TET2 hits within the clonal hierarchy. Using deep sequencing, 1781 mutations were found in 1205 of 4930 patients; 40% of mutant cases were biallelic. Hierarchical analysis revealed that of TET2MT cases >40% were ancestral, e.g., representing 8% of MDS. Higher (earlier) TET2 lesion rank within the clonal hierarchy (greater clonal burden) was associated with impaired survival. Moreover, MDS driven by ancestral TET2MT is likely derived from TET2MT CHIP with a penetrance of ~1%. Following ancestral TET2 mutations, individual disease course is determined by secondary hits. Using multidimensional analyses, we demonstrate how hits following the TET2 founder defect induces phenotypic shifts toward dysplasia, myeloproliferation, or progression to AML. In summary, TET2MT CHIP-derived MDS is a subclass of MDS that is distinct from de novo disease. PMID- 29795414 TI - Risk of subsequent myeloid neoplasms after radiotherapy treatment for a solid cancer among adults in the United States, 2000-2014. AB - Although increased risk of acute myeloid leukemia (AML) has been observed after chemotherapy and radiotherapy, less is known about radiotherapy-related risks of specific AML subtypes and other specific myeloid neoplasms. We used the US population-based cancer registry data to evaluate risk of myeloid neoplasms among three cohorts of cancer survivors initially treated with radiotherapy only. We included 1-year survivors of first primary thyroid (radioiodine only, stages I IV; N = 49 879), prostate (excluding stage IV; N = 237 439), or uterine corpus cancers (stage I-II; N = 16 208) diagnosed during 2000-2013. We calculated standardized incidence ratios (SIRs) and excess absolute risks (EARs). Thyroid cancer survivors had significantly elevated risks of total AML (SIR = 2.77, 95% CI: 1.99-3.76), AML with cytogenetic abnormalities (SIR = 3.90, 95% CI: 1.57 8.04), AML with myelodysplasia-related changes (SIR = 2.87, 95% CI: 1.05-6.25), and BCR-ABL1-positive chronic myelogenous leukemia (CML) (SIR = 5.38, 95% CI: 2.58-9.89). Irradiated prostate and uterine corpus cancer survivors were at elevated risk for total AML (SIR = 1.14, 95% CI: 1.03-1.27 and SIR = 1.77, 95% CI: 1.01-2.87, respectively), AML with cytogenetic abnormalities (SIR = 2.52, 95% CI: 1.84-3.37 and SIR = 7.21, 95% CI: 2.34-16.83, respectively), and acute promyelocytic leukemia (SIR = 3.20, 95% CI: 2.20-4.49 and SIR = 8.88, 95% CI: 2.42-22.73, respectively). In addition, prostate cancer survivors were at increased risk of BCR-ABL1-positive CML (SIR = 2.11, 95% CI: 1.52-2.85). Our findings support the importance of diagnostic precision in myeloid neoplasm classification since susceptibility following radiotherapy may vary by myeloid neoplasm subtype, thereby informing risk/benefit discussions in first primary cancer treatment. PMID- 29795416 TI - Foscarnet treatment of cytomegalovirus infection in haploidentical or unrelated donor transplants. AB - We studied 97 patients who developed cytomegalovirus (CMV) viremia following an allogeneic hemopoietic stem cell transplant (HSCT) between 2010 and 2015, treated with foscarnet, with the aim of assessing efficacy and safety. The donor was unrelated in 30 patients (UD) and a family HLA-haploidentical donor (HAPLO) in 67 patients: the former (UD) received a prophylaxis for graft-versus-host disease (GvHD), based on antithymocyte globulin (ATG); the latter (HAPLO) received GvHD prophylaxis, based on post-transplant cyclophosphamide (PT-CY). Renal and hematological toxicity were defined according to NCI-CTCAE4 criteria. In univariate analysis, CMV response was 84% in HAPLO vs 59% in UD grafts (p = 0.01) and 90 vs 66% (p = 0.02) for patients with a CMV viral load within or over the median value. In multivariate analysis, the CMV viral load was the strongest predictor of response to foscarnet (p = 0.02), followed by donor type (p = 0.06). Renal impairment developed in 14% of the patients. Overall survival was 69%:, advanced phase at transplant (p = 0.01) and ATG-based regimens (p = 0.02), were the only two predicting factor. In conclusion, CMV response to foscarnet treatment is predicted by a lower CMV load and GvHD prophylaxis. Renal toxicity of foscarnet is not a limiting factor. PMID- 29795415 TI - Self-management interventions for skin care in people with a spinal cord injury: part 2-a systematic review of use of theory and quality of intervention reporting. AB - STUDY DESIGN: Systematic review. OBJECTIVES: To examine use of theory and quality of reporting in skin care self-management interventions for people with SCI. SETTING: International. METHODS: The Theory Coding Scheme (TCS) and the Template for Intervention Description and Replication (TIDieR) checklist were applied by two independent researchers to 17 interventions identified in a systematic review of self-management interventions for skin care in people with SCI. RESULTS: Six (35%) of the 17 interventions reviewed were reported to have a theoretical basis. Theories used included three of the most commonly featured in health behavior research (the Health Belief Model, Social Cognitive Theory, and the Transtheoretical Model). In these six interventions, theory was used to design content but not to select participants or tailor strategies. None of the interventions were used to test theories in the SCI population, or to propose theoretical refinements. Reporting quality was found to vary by TIDieR item, with 6-100% of interventions including recommended information. Information on two intervention fidelity items was missing in 53 and 82% of descriptions. CONCLUSIONS: Use of theory and reporting quality in SCI self-management research remains suboptimal, potentially slowing down advancements in this area of research. Rehabilitation researchers should direct their efforts toward improving these practices to help build a science of SCI self-management that is cumulative and reproducible by clinicians, scientists, and policy makers. SPONSORSHIP: This work was funded through a postdoctoral fellowship awarded to the first author by the Rick Hansen Institute. PMID- 29795417 TI - Bloodless tandem autologous transplant in Jehovah's Witness patients. AB - Tandem autologous transplants are generally the preferred therapy for newly diagnosed intermediate- and high-risk myeloma patients. More Jehovah's Witnesses (JW) are receiving single autologous peripheral blood stem cell transplants (PBSCTs). However, tandem autologous transplants have not been reported in JW patients. We performed a retrospective study of 54 patients, including four JW patients who received tandem autologous transplants between August 2000 and January 2017 and the last 50 consecutive tandem autologous transplants performed between August 2014 and August 2016. The bleeding complications, number, and cost of transfusions of blood products were compared. The median number of CD34 cells infused in non-JW patients was 8.16 million cells/kg versus 9.44 million cells/kg in JW patients. During the first 30 days, one JW experienced Grade III pulmonary hemorrhage, while none of the non-JW patients had a Grade III or higher bleeding problem. After tandem autologous transplants, complete remission was achieved in 88% of non-JW, compared with 75% in JW patients. In the first 30 days post transplant, median platelet and packed red blood cell (PRBC) transfusions in non JW patients was 2 (range: 0-40) and 1 (range: 0-11), respectively. Total cost of PRBC and platelet transfusions for the 50 non-JW was $214,664 (average $2147/transplant). Tandem autologous transplants can thus be performed safely without a single blood transfusion. PMID- 29795418 TI - Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts. AB - Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 * 107/kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution. PMID- 29795419 TI - Long-term aprepitant for nausea and vomiting associated with gastroparesis in hematopoietic stem cell transplantation. PMID- 29795420 TI - The efficacy of salvage autologous stem cell transplant among patients with multiple myeloma who received maintenance therapy post initial transplant. PMID- 29795421 TI - Does marital status affect the outcomes after allogeneic hematopoietic cell transplantation? PMID- 29795422 TI - Plerixafor in non-Hodgkin's lymphoma patients: a German analysis of time, effort and costs. AB - Mobilization and collection of peripheral blood stem cells is part of the standard treatment procedure for non-Hodgkin's lymphoma patients eligible for high-dose chemotherapy with autologous stem cell transplantation. Mobilization is usually achieved with chemotherapy and/or cytokines, but plerixafor might be added in case of poor mobilization. Due to the high cost several institutions have developed their own management pathway to optimize use of plerixafor. Such models are however rarely generalizable; in a multi-center, European, non interventional study, evaluating the impact of plerixafor in poor mobilizers, country specific differences in patient treatment and cost structure were obvious. For German centers, there was a non-significant reduction in the number of apheresis sessions carried out and in apheresis costs. In contrast to other European countries the majority of German Plerixafor patients were very poor mobilizing patients with initial CD34+ cell count <= 10/ul (40/51). In this group the number of apheresis sessions decreased from 2.1 to 1.6 sessions per patient (p = 0.01) and costs decreased from ?6246 to ?4758 (p = 0.01). Our results show that preemptive plerixafor use has a strong effect in poor mobilizers with an initial CD34+ cell count <= 10 cells/ul. PMID- 29795423 TI - Decision analysis of up-front autologous hematopoietic stem cell transplantation in patients with peripheral T-cell lymphoma. PMID- 29795425 TI - Invasive aspergillosis in patients following umbilical cord blood transplant. PMID- 29795424 TI - HHV-6B infection, T-cell reconstitution, and graft-vs-host disease after hematopoietic stem cell transplantation. AB - Successful and sustained CD4+ T-cell reconstitution is associated with increased survival after hematopoietic cell transplantation (HCT), but opportunistic infections may adversely affect the time and extent of immune reconstitution. Human herpesvirus 6B (HHV-6B) efficiently infects CD4+ T cells and utilizes as a receptor CD134 (OX40), a member of the TNF superfamily that antagonizes regulatory T-cell (Treg) activity. Reactivation of HHV-6B has been associated with aberrant immune reconstitution and acute graft-versus-host disease (aGVHD) after HCT. Given that Treg counts are negatively correlated with aGVHD severity, we postulate that one mechanism for the poor CD4+ T-cell reconstitution observed shortly after transplant may be HHV-6B infection and depletion of peripheral (extra-thymic) CD4+ T cells, including a subpopulation of Treg cells. In turn, this may trigger a series of adverse events resulting in poor clinical outcomes such as severe aGVHD. In addition, recent evidence has linked HHV-6B reactivation with aberrant CD4+ T-cell reconstitution late after transplantation, which may be mediated by a different mechanism, possibly related to central (thymic) suppression of T-cell reconstitution. These observations suggest that aggressive management of HHV-6B reactivation in transplant patients may facilitate CD4+ T cell reconstitution and improve the quality of life and survival of HCT patients. PMID- 29795426 TI - Prevention and treatment of relapse after stem cell transplantation by cellular therapies. AB - Despite recent advances in reducing therapy-related mortality after allogeneic stem cell transplantation (alloSCT) relapse remains the major cause of treatment failure and little progress has been achieved in the last decades. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg/Germany in November 2016 international experts presented and discussed recent developments in the field. Here, the potential of cellular therapies including unspecific and specific T cells, genetically modified T cells, CAR-T cells, NK-cells, and second allografting in prevention and treatment of relapse after alloSCT are summarized. PMID- 29795427 TI - Prevention and treatment of relapse after stem cell transplantation with immunotherapy. AB - Relapse has become the leading cause of treatment failure after stem cell transplantation. Besides cellular therapies and novel agents, immunotherapeutic strategies have entered clinical practice in order to reduce or prevent relapse. Here, we summarize the presentations on checkpoint inhibitors, vaccination strategies, and novel antibody therapies, which were presented and discussed at the third International Workshop on Biology, Prevention, and Treatment of Relapse after Stem Cell Transplantation. PMID- 29795428 TI - Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. AB - Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage. PMID- 29795429 TI - Tocilizumab for the treatment of severe steroid-refractory acute graft-versus host disease of the lower gastrointestinal tract. AB - Steroid-refractory (SR) acute gastrointestinal (GI) graft-versus-host disease (GVHD) is associated with significant mortality in allogeneic hematopoietic cell transplantation recipients. We retrospectively evaluated the efficacy of tocilizumab for the treatment of SR biopsy-proven acute lower GI GVHD in 16 consecutive adult transplant recipients between October 2015 and July 2016. Tocilizumab 8 mg/kg was administered every 2 weeks until achievement of complete response, defined as resolution of all manifestations of GI GVHD, or until patients had progression or initiation of other therapy. Ten of 16 patients (62.5%; 95% CI, 0.39-82) achieved a complete response after a median time of 11 days (range, 2-28 days) from tocilizumab initiation. The median time to response onset (improvement in stage by at least 1) was 1 day (range, 1-4 days). Tocilizumab was administered at a median of 9 days (range, 3-75 days) from GVHD diagnosis and 10 days (range, 3-75 days) from initiation of high-dose steroids. At a median follow-up of 7.6 months (range, 0.8-27.7 months) from initiation of tocilizumab, 6/16 (37.5%) patients are alive and free of their underlying hematologic malignancy. Tocilizumab appears to be a highly active agent for the treatment of severe SR lower GI acute GVHD. PMID- 29795430 TI - Depletion of donor-specific anti-HLA A2 alloantibodies in a hematopoietic cell transplant recipient using directed mismatched platelet transfusions. PMID- 29795431 TI - Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis. AB - The aim of this study is to compare clinical outcomes of patients who underwent allogeneic stem cell transplantation (HCT) for myelofibrosis with reduced intensity conditioning (RIC) using either Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/ carmustine Melphalan (FBM) or Fludarabine Melphalan (FluMel) regimens. Sixty-one patients were identified who underwent HCT with one of these RIC regimens. Overall survival (OS) was not different in the 3 groups. However, 100% donor chimerism was seen in more frequently at day +30 and day +100 in patients who received FBM or FluMel than BuFlu, in both CD3 and CD33 fractions. For instance, 100% donor chimerism in CD33 fraction was present in 100% patients in FBM cohort, 90% in FluMel cohort while 44% in BuFlu cohort at day +100. Acute graft-versus host disease, grade 2-4 and grade 3-4, was not statistically different in the 3 groups (BuFlu 47 and 35%, FBM 68 and 27%, FluMel 68 and 46%; p = 0.31 and 0.45). Relapses and non-relapse mortality was also not statistically significantly different. Our study shows similar OS with these 3 RIC regimens in myelofibrosis; although donor chimerism at day +30 and day +100 was better in patients who received FBM and FluMel. PMID- 29795432 TI - CAR T cells induce a complete response in refractory Burkitt Lymphoma. PMID- 29795433 TI - Prevention and treatment of relapse after stem cell transplantation in lymphoid malignancies. AB - Relapse is now the major cause of treatment failure after allogeneic HSCT (alloHSCT). Many novel strategies to address this critical issue are now being developed and tested. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg, Germany in November 2016, international experts presented and discussed recent developments in the field. Some approaches may be applicable to a wide range of patients after transplant, whereas some may be very disease-specific. We present a report from the session dedicated to issues related to prevention and treatment of relapse of lymphoid malignancies after alloHSCT. This session included detailed reviews as well as forward-looking commentaries that focused on Hodgkin lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma, diffuse large cell and follicular lymphoma, and multiple myeloma. PMID- 29795434 TI - Poor prognosis in patients with steroid refractory acute graft versus host disease treated with etanercept: a multi-centre analysis. PMID- 29795435 TI - Prevention of relapse after allogeneic hematopoietic cell transplantation by donor and cell source selection. AB - Allogeneic hematopoietic cell transplantation (HCT) is the most established form of cancer immunotherapy and has been successfully applied for the treatment and cure of otherwise lethal neoplastic blood disorders. Cancer immune surveillance is mediated to a large extent by alloreactive T and natural killer (NK) cells recognizing genetic differences between patient and donor. Profound insights into the biology of these effector cells has been obtained over recent years and used for the development of innovative strategies for intelligent donor selection, aiming for improved graft-versus-leukemia effect without unmanageable graft versus-host disease. The cellular composition of the stem cell source plays a major role in modulating these effects. This review summarizes the current state of the-art of donor selection according to HLA, NK alloreactivity and stem cell source. PMID- 29795436 TI - Impact of body mass index at different transplantation stages on postoperative outcomes in patients with hematological malignancies: a meta-analysis. AB - Although the association between body mass index (BMI) and overall survival (OS) has been reported in leukemia patients of different ages, whether BMI levels at different stages of hematopoietic stem cell transplantation (HSCT) have different effects on postoperative survival remains controversial. We searched four electronic databases from inception through July 2017 without any language restrictions and included studies on different types of hematological malignancies reporting both BMI time points and HSCT. Of the 1420 articles identified, 26 articles were eligible for inclusion in this meta-analysis. Three weight groups (obese, overweight and underweight) were individually compared with the normal group. Summary risk estimates for OS and event-free survival (EFS) were calculated with random- or fixed-effects models. For BMI at the pre-HSCT stage, a statistically significant positive association of increased risk of OS (RR: 1.17; 95% CI: 1.08-1.27) and EFS (RR: 1.29; 95% CI: 1-1.67) was identified in underweight individuals compared with those with normal weights. For BMI in the HSCT stage, a lower BMI was significantly associated with poorer OS (RR: 1.34; 95% CI: 1.01-1.78) and EFS (RR: 1.53; 95% CI: 1.09-2.06) compared with a normal BMI. Our results indicated that lower BMI at the pre-HSCT stage or during HSCT is associated with poorer survival. PMID- 29795438 TI - Number, not size, of mesenteric tumor deposits affects prognosis of small intestinal well-differentiated neuroendocrine tumors. AB - Mesenteric tumor deposits are an adverse prognostic factor for small intestinal well-differentiated neuroendocrine tumors. Per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (eighth edition), any mesenteric tumor deposit larger than 2 cm signifies pN2 disease. This criterion has not been critically evaluated as a prognostic factor for small intestinal neuroendocrine tumors, nor have multifocality or histologic features of mesenteric tumor deposits. We evaluated 70 small intestinal neuroendocrine tumors with mesenteric tumor deposits for lesional contour, sclerosis, inflammation, calcification, entrapped blood vessels, and perineural invasion. Ki67 proliferative indices of the largest mesenteric tumor deposit from each case were calculated, and number of tumor deposits and size of the largest deposit were recorded. Associations between these factors (along with patient age, primary tumor Ki67 index, and AJCC stage) and development of liver metastases and overall survival were assessed. Median mesenteric tumor deposit size was 1.5 cm (range: 0.2-7.0 cm); median deposit number was 1 (range: 1-13). Primary and tumor deposit Ki67 indices within a given patient were discordant in 40% of cases but showed similar hazard ratios for disease-specific survival. Size of tumor deposits had no significant effect on prognosis, whether analyzed on a continuous scale or dichotomized using the recommended 2 cm cutoff. In contrast, increasing number of deposits was associated with poor prognosis, with multiple deposits conferring an 8.19-fold risk of disease-specific death compared to a single deposit (P = 0.049). Morphologic features of deposits had no prognostic impact. Size of mesenteric tumor deposits does not affect prognosis in small intestinal neuroendocrine tumor patients; instead, deposit multifocality is associated with shorter disease specific survival and should be incorporated into future staging criteria. PMID- 29795437 TI - Nuclear beta-catenin localization and mutation of the CTNNB1 gene: a context dependent association. AB - Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes beta-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the beta-catenin protein from the membrane to the nucleus and activation of Wnt/beta-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of beta-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of beta-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5-10% of tumor cells with beta-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of beta-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of beta-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of beta-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of beta-catenin is absent. PMID- 29795439 TI - Response to Roberts et al. 2018: is breast cancer truly caused by MSH6 and PMS2 variants or is it simply due to a high prevalence of these variants in the population? PMID- 29795440 TI - Response to ten Broeke et al. PMID- 29795441 TI - Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. AB - Ageing is the main risk factor for the development of cardiovascular diseases. A central mechanism by which ageing promotes vascular pathologies is compromising endothelial health. The age-related attenuation of endothelium-dependent dilator responses (endothelial dysfunction) associated with impairment of angiogenic processes and the subsequent pathological remodelling of the microcirculation contribute to compromised tissue perfusion and exacerbate functional decline in older individuals. This Review focuses on cellular, molecular, and functional changes that occur in the endothelium during ageing. We explore the links between oxidative and nitrative stress and the conserved molecular pathways affecting endothelial dysfunction and impaired angiogenesis during ageing. We also speculate on how these pathological processes could be therapeutically targeted. An improved understanding of endothelial biology in older patients is crucial for all cardiologists because maintenance of a competently functioning endothelium is critical for adequate tissue perfusion and long-term cardiac health. PMID- 29795443 TI - Computer modelling to personalize bioengineered heart valves. PMID- 29795442 TI - Exercising engineered heart muscle to maturity. PMID- 29795444 TI - The oncogenic fusion protein CBFB-SMMHC downregulates CD48 to evade NK cell recognition. PMID- 29795445 TI - MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models. AB - Activation of the mitogen-activated protein kinase (MAPK) pathway is frequent in cancer. Drug development efforts have been focused on kinases in this pathway, most notably on RAF and MEK. We show here that MEK inhibition activates JNK-JUN signaling through suppression of DUSP4, leading to activation of HER Receptor Tyrosine Kinases. This stimulates the MAPK pathway in the presence of drug, thereby blunting the effect of MEK inhibition. Cancers that have lost MAP3K1 or MAP2K4 fail to activate JNK-JUN. Consequently, loss-of-function mutations in either MAP3K1 or MAP2K4 confer sensitivity to MEK inhibition by disabling JNK-JUN mediated feedback loop upon MEK inhibition. In a panel of 168 Patient Derived Xenograft (PDX) tumors, MAP3K1 and MAP2K4 mutation status is a strong predictor of response to MEK inhibition. Our findings suggest that cancers having mutations in MAP3K1 or MAP2K4, which are frequent in tumors of breast, prostate and colon, may respond to MEK inhibitors. Our findings also suggest that MAP3K1 and MAP2K4 are potential drug targets in combination with MEK inhibitors, in spite of the fact that they are encoded by tumor suppressor genes. PMID- 29795446 TI - The BH3-only protein BAD mediates TNFalpha cytotoxicity despite concurrent activation of IKK and NF-kappaB in septic shock. AB - The inflammatory cytokine TNFalpha plays a crucial role in the pathology of many inflammatory and infectious diseases. However, the mechanism underlying TNFalpha cytotoxicity in these diseases is incompletely understood. Here we report that the pro-apoptotic BCL-2 family member BAD mediates TNFalpha cytotoxicity despite concurrent activation of IKK and NF-kappaB in vitro by inducing apoptosis in cultured cells and in vivo by eliciting tissue damage of multiple organs and contributing to mortality in septic shock. At high doses, TNFalpha significantly inactivates RhoA through activation of the Src-p190GAP pathway, resulting in massive actin stress fiber destabilization, followed by substantial BAD release from the cytoskeleton to the cytosol. Under this condition, activated IKK fails to phosphorylate all cytosolic BAD, allowing translocation of non-phosphorylated BAD to mitochondria to trigger apoptosis. Polymicrobial infection utilizes the same mechanism as high-dose TNFalpha to elicit apoptosis-associated tissue damage of multiple organs. Consequently, loss of Bad or elimination of BAD pro-apoptotic activity protects mice from tissue damage of multiple organs and reduces mortality rates. Our results support a model in which BAD mediates TNFalpha cytotoxicity despite concurrent activation of the IKK-NF-kappaB pathway in cultured mammalian cells and in septic shock. PMID- 29795447 TI - Burkholderia bacteria use chemotaxis to find social amoeba Dictyostelium discoideum hosts. AB - A key question in cooperation is how to find the right partners and maintain cooperative relationships. This is especially challenging for horizontally transferred bacterial symbionts where relationships must be repeatedly established anew. In the social amoeba Dictyostelium discoideum farming symbiosis, two species of inedible Burkholderia bacteria (Burkholderia agricolaris and Burkholderia hayleyella) initiate stable associations with naive D. discoideum hosts and cause carriage of additional bacterial species. However, it is not clear how the association between D. discoideum and its carried Burkholderia is formed and maintained. Here, we look at precisely how Burkholderia finds its hosts. We found that both species of Burkholderia clones isolated from D. discoideum, but not other tested Burkholderia species, are attracted to D. discoideum supernatant, showing that the association is not simply the result of haphazard engulfment by the amoebas. The chemotactic responses are affected by both partners. We find evidence that B. hayleyella prefers D. discoideum clones that currently or previously carried Burkholderia, while B. agricolaris does not show this preference. However, we find no evidence of Burkholderia preference for their own host clone or for other hosts of their own species. We further investigate the chemical differences of D. discoideum supernatants that might explain the patterns shown above using a mass spectrometry based metabolomics approach. These results show that these bacterial symbionts are able to preferentially find and to some extent choose their unicellular partners. In addition, this study also suggests that bacteria can actively search for and target phagocytic cells, which may help us better understand how bacteria interact with immune systems. PMID- 29795448 TI - Species-specific transcriptomic network inference of interspecies interactions. AB - The advent of high-throughput 'omics approaches coupled with computational analyses to reconstruct individual genomes from metagenomes provides a basis for species-resolved functional studies. Here, a mutual information approach was applied to build a gene association network of a commensal consortium, in which a unicellular cyanobacterium Thermosynechococcus elongatus BP1 supported the heterotrophic growth of Meiothermus ruber strain A. Specifically, we used the context likelihood of relatedness (CLR) algorithm to generate a gene association network from 25 transcriptomic datasets representing distinct growth conditions. The resulting interspecies network revealed a number of linkages between genes in each species. While many of the linkages were supported by the existing knowledge of phototroph-heterotroph interactions and the metabolism of these two species several new interactions were inferred as well. These include linkages between amino acid synthesis and uptake genes, as well as carbohydrate and vitamin metabolism, terpenoid metabolism and cell adhesion genes. Further topological examination and functional analysis of specific gene associations suggested that the interactions are likely to center around the exchange of energetically costly metabolites between T. elongatus and M. ruber. Both the approach and conclusions derived from this work are widely applicable to microbial communities for identification of the interactions between species and characterization of community functioning as a whole. PMID- 29795449 TI - Tight glycemic control in critically ill pediatric patients: a meta-analysis and systematic review of randomized controlled trials. AB - BACKGROUND: There still are controversies in the impact of tight glycemic control (TGC) in critically ill children. The aim of this study was to assess the benefits and risks of TGC compared with conventional glycemic control (CGC) in critically ill pediatric patients admitted to the pediatric intensive care unit (PICU) by using data retrieved from randomized controlled trials (RCTs). METHOD: EMBASE, CNKI, PubMed, and the Cochrane Database were searched for RCTs comparing TGC with CGC in critically ill children in PICU. RESULT: The meta-analysis included five RCTs representing 3933 patients and compared TGC with CGC. Our result revealed that TGC did not reduce the 30-day mortality rates (OR 0.99, 95% CI 0.74-1.32, P = 0.95) and was not associated with decreasing health care associated infections (OR 0.80, 95% CI 0.64-1.00, P = 0.05) compared with CGC, but significantly increased the incidence of hypoglycemia (OR 6.37, 95% CI 4.41 9.21, P < 0.001). CONCLUSION: Tight glycemic control was not associated with reducing the 30-day mortality rates and acquired infections compared with CGC in critically ill children. Significant increase of the incidence of hypoglycemia was revealed in TGC group. The conclusion should be interpreted with caution for the methodological heterogeneity among trials. PMID- 29795452 TI - A randomized controlled trial: does coaching using video during direct laryngoscopy improve residents' success in neonatal intubations? AB - OBJECTIVE: To evaluate the intubation success rates of residents who receive coaching from supervisors concurrently viewing infants' airways via video during direct laryngoscopy (VDL), as compared with coaching during traditional direct laryngoscopy without video (TDL). STUDY DESIGN: In a randomized controlled trial, 48 first and second-year residents performed neonatal intubations using VDL or TDL. The primary outcome was intubation success rates. Data were analyzed using the Pearson X2 and Student's t-test. RESULTS: The overall intubation success rate was greater in the VDL vs. TDL group (57% vs. 33%, P < 0.05). First-year residents and residents intubating their first patient had higher intubation success rates in the VDL vs. TDL group (58% vs. 23% and 50% vs. 17%, respectively, P < 0.05). CONCLUSIONS: Resident coaching using VDL improved neonatal intubation success rates. Incorporating VDL as a coaching tool can optimize the quality of training during limited opportunities to achieve procedural competency and improve intubation-related patient outcomes. PMID- 29795450 TI - Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics. AB - OBJECTIVE: To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (+/-) preeclampsia. STUDY DESIGN: Included were 400 women with singleton deliveries in California in 2009 2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB +/- preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION: Together with maternal age and poverty status, mid pregnancy immune and growth factors reliably identified most women who went on to have a PTB +/- preeclampsia. PMID- 29795451 TI - Informed consent for a neonatal clinical trial: parental experiences and perspectives. AB - OBJECTIVE: There is a variability regarding timing of consent and personnel used in patient recruitment for neonatal research. We explored the associations between the study personnel and timing of consent with parents' decisional conflict and ultimately their decision to enroll. STUDY DESIGN: This was a multi site, cross-sectional survey conducted between August 2015 and October 2017. Participants were parents approached to enroll their 24-28-week infant in a clinical trial. Parents completed an interviewer-administered 61-item questionnaire. RESULTS: Overall, 163 surveys were completed; 105 by parents of enrolled infants and 58 by parents of non-enrolled infants (54.5% participation rate). Neither the individual requesting nor timing of consent was associated with parents' knowledge score, decisional conflict, or decision to enroll. Parents preferred to be approached prenatally and by their infant's doctor. CONCLUSION: Study designers and IRBs may allow flexibility in personnel and timing of consent as it is respectful of parents and may enhance trial enrollment. PMID- 29795453 TI - NICU management and outcomes of infants with trisomy 21 without major anomalies. AB - OBJECTIVE: To describe how trisomy 21 affects neonatal intensive care management and outcomes of full-term infants without congenital anomalies. STUDY DESIGN: Retrospective cohort of full-term infants without anomalies with and without trisomy 21 admitted to Pediatrix NICUs from 2005 to 2012. We compared diagnoses, management, length of stay, and discharge outcomes. RESULTS: In all, 4623 infants with trisomy 21 and 606 770 infants without trisomy 21 were identified. One-third of infants in the NICU with and without trisomy 21 were full term without major anomalies. Trisomy 21 infants had more respiratory distress, thrombocytopenia, feeding problems, and pulmonary hypertension. They received respiratory support for a longer period of time and had a longer length of stay. CONCLUSION: One third of infants with trisomy 21 admitted to the NICU are full term without major anomalies. Common diagnoses and greater respiratory needs place infants with trisomy 21 at risk for longer length of stay. PMID- 29795454 TI - Early determinants of metabolically healthy obesity in young adults: study of the Northern Finland Birth Cohort 1966. AB - BACKGROUND: A body of literature suggests a metabolically healthy phenotype in individuals with obesity. Despite important clinical implications, the early origins of metabolically healthy obesity (MHO) have received little attention. OBJECTIVE: To assess the prevalence of MHO among the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years of age, examine its determinants in early life taking into account the sex specificity. METHODS: We studied 3205 term-born cohort participants with data available for cardio-metabolic health outcomes at 31 years, and longitudinal height and weight data. After stratifying the population by sex, adult BMI and a strict definition of metabolic health (i.e., no risk factors meaning metabolic health), we obtained six groups. Repeated childhood height and weight measures were used to model early growth and early adiposity phenotypes. We employed marginal means adjusted for mother and child covariates including socio-economic status, birth weight and gestational-age, to compare differences between the groups. RESULTS: The prevalence of adult MHO was 6% in men and 13.5% in women. Differences in adult metabolic status were linked to alterations in BMI and age at adiposity peak in infancy (p < 0.0003 in men and p = 0.027 in women), and BMI and age at adiposity rebound (AR) (p < 0.0001 irrespective of sex). Compared to MHO, metabolically unhealthy obese (MUO) women were five and a half months younger at AR (p = 0.007) with a higher BMI while MUO men were four months older (p = 0.036) with no difference in BMI at AR. CONCLUSION: At the time of AR, MHO women appeared to be older than their MUO counterparts while MHO men were younger. These original results support potential risk factors at the time of adiposity rebound linked to metabolic health in adulthood. These variations by sex warrant independent replication. PMID- 29795455 TI - Minor diplotypes of FMO3 might protect children and adolescents from obesity and insulin resistance. AB - In order to assess whether flavin-containing monooxygenase-3 (FMO3) might be involved in early cardiovascular risk, we assessed adiposity and traditional metabolic variables in children/adolescents grouped according to their genotypes in two FMO3 exonic polymorphisms, rs2266782 (E158K) and rs2266780 (E308G), which are in linkage disequilibrium and have been associated with decreased FMO3 activity. Among 776 children/adolescents (10.8 +/- 2.2 years) recruited from the general population (452) and from our obesity outpatient clinic (324), the 68 carrying either the 158K-308G/158K-308E or the 158K-308G/158K-308G diplotype had lower mean z-BMI and prevalence of obesity compared to their 708 peers carrying any of the other diplotypes (0.39 vs 0.80, p = 0.01; OR = 0.39[0.17-0.87], p = 0.018, respectively), and to the sub-sample of 303 children carrying the major diplotype (158E-308E/158E-308E) (0.39 vs 0.87, p = 0.008; OR = 0.35[0.16-0.81], p = 0.014, respectively). They also had lower z-BMI-adjusted lnHOMA-IR compared to all the other children (0.75 vs 0.97, p = 0.001) and those carrying the major diplotype, (0.75 vs 0.98, p = 0.03), as well as lower z-BMI-adjusted iln triglycerides compared to all the other children (3.98 vs 4.17, p = 0.037). These associations provide the first evidence that FMO3 may be involved in early body weight, insulin sensitivity, and lipid regulation in humans. PMID- 29795456 TI - Rosiglitazone reverses high fat diet-induced changes in BMAL1 function in muscle, fat, and liver tissue in mice. AB - OBJECTIVE: Nutrient challenge in the form of a high fat (HF) diet causes a reversible reprogramming of the hepatic circadian clock. This depends in part on changes in the recruitment of the circadian transcription factor BMAL1 to genome targets, though the causes and extent of disruption to hepatic and extra-hepatic BMAL1 are unknown. The objective of the study was to determine whether HF diet induced alterations in BMAL1 function occur across insulin-resistant tissues and whether this could be reversed by restoring whole body insulin sensitivity. METHODS: BMAL1 subcellular localization and target recruitment was analyzed in several metabolically active peripheral tissues, including liver, muscle, and adipose tissue under conditions of diet-induced obesity. Animals made obese with HF diet were subsequently treated with rosiglitazone to determine whether resensitizing insulin-resistant tissues to insulin restored hepatic and extra hepatic BMAL1 function. RESULTS: These data reveal that both hepatic and extra hepatic BMAL1 activity are altered under conditions of obesity and insulin resistance. Restoring whole body insulin sensitivity by treatment with the antidiabetic drug rosiglitazone is sufficient to restore changes in HF diet induced BMAL1 recruitment and activity in several tissues. CONCLUSIONS: This study reveals that a key mechanism by which HF diet interferes with clock function in peripheral tissues is via the development of insulin resistance. PMID- 29795457 TI - Framing obesity a disease: Indirect effects of affect and controllability beliefs on weight bias. AB - BACKGROUND/OBJECTIVES: Obesity has been declared a disease by the American and Canadian Medical Associations. Although these declarations sparked much debate as to the impact of framing obesity as a disease on weight bias, strong empirical research is needed to examine this impact. The current study examined the impact of framing obesity a disease on weight bias, focusing on moderating and mediating processes. SUBJECTS/METHODS: A sample of 309 participants living in the United States or Canada was recruited from Crowdflower. Participants completed measures of demographics, ideology, general attitudes, and previous contact quality and quantity with people living with obesity. Participants then read one of three articles as part of an experimental manipulation framing obesity as a disease, obesity not as a disease, and a control article unrelated to obesity. Post manipulation included measures of affect, disgust, empathy, blame, and weight bias. RESULTS: Orthogonal contrasts were used to compare the obesity-disease condition to the obesity-not-disease condition and control condition. The manipulation had a direct effect on affect (emotions), such that affect toward individuals with obesity was more positive in the obesity-disease condition than the obesity-not-disease and control condition combined. Exploration of moderating effects revealed that both the belief in a just world and weight satisfaction moderated the relationship between the obesity-disease manipulation and blame for obesity. Two models of indirect effects on weight bias were also examined, which demonstrated that the obesity-disease manipulation predicted less weight bias through more positive affect (model 1) as well as less weight bias through decreased blame among individuals high in belief in a just world (model 2). CONCLUSIONS: This study further highlights the complex effects of declaring obesity a disease, uncovering a new direction for future research into the role of affect as well as indirect effects of characterising obesity a disease on weight bias. PMID- 29795458 TI - Maternal preconception weight trajectories are associated with offsprings' childhood obesity. AB - OBJECTIVES: This study aimed to examine the associations between (1) mothers' preconception body mass index (BMI) trajectories over 6-7 years and offspring childhood BMI, and (2) mothers' BMI changes between first and second pregnancy and the second-born child's BMI. METHODS: We used data (1606 mothers with 2733 children with mean age 7.7 years, SD 2.9) from the Australian Longitudinal Study on Women's Health and the Mothers and their Children's Health study. Preconception BMI trajectories were identified using latent class growth modeling. Children were categorized as underweight, normal, overweight or obese based on age and sex-specific BMI cut-off points for children. Multinomial and binary logistic regression were used for analyses. RESULTS: We identified three preconception BMI trajectories, named as 'normative' (61.2%), 'chronically overweight' (30.7%), and 'chronically obese' (8.1%). Children born to 'chronically overweight' and 'chronically obese' mothers were more likely to be overweight than normal weight relative to children born to women with a 'normative' BMI trajectory. The corresponding adjusted relative risk ratios (RRRs) (95% confidence interval [CI]) of childhood overweight were 1.75 (1.33, 2.31) for chronically overweight mothers and 2.48 (1.65, 3.73) for chronically obese mothers. Similarly, we found a much stronger association between 'chronically overweight' and 'chronically obese' BMI trajectories and childhood risk of obesity; RRR (95% CI), 2.49 (1.41, 4.40) and 6.65 (3.40, 13.01), respectively. Second-born children of mothers with high interpregnancy weight gain (>=4 BMI units) were also at higher risk of being overweight or obese (OR = 2.20, 95% CI: 1.02, 4.75) compared with children of mothers with stable interpregnancy weight (gain or loss of 1 BMI unit or less). CONCLUSIONS: In this population-based prospective cohort study, we found strong dose-response associations between preconception BMI trajectories and offsprings' childhood BMI. PMID- 29795459 TI - Kinetics of human brown adipose tissue activation and deactivation. AB - Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7 +/- 0.7 kg/m2, Age: 31.2 +/- 2.8 year, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 min of pre-injection cooling produces activation similar to the standard 60 min (39.9 mL vs. 44.2 mL, p = 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p = 0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease. PMID- 29795461 TI - Epigallocatechin gallate targets FTO and inhibits adipogenesis in an mRNA m6A YTHDF2-dependent manner. AB - BACKGROUND/OBJECTIVE: N6-methyladenosine (m6A) modification of mRNA plays a role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, plays a critical role in anti-obesity and anti-adipogenesis. METHODS: High performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS) was performed to determine the m6A levels in 3T3-L1 preadipocytes. The effects of EGCG on the m6A levels in specific genes were determined by methylated RNA immunoprecipitation coupled with quantitative real time PCR (meRIP-qPCR). Several adipogenesis makers and cell cycle genes were analyzed by quantitative real-time PCR (qPCR) and western blotting. Lipid accumulation was evaluated by oil red O staining. All measurements were performed at least for three times. RESULTS: Here we showed that EGCG inhibited adipogenesis by blocking the mitotic clonal expansion (MCE) at the early stage of adipocyte differentiation. Exposing 3T3-L1 cells to EGCG reduced the expression of fat mass and obesity-associated (FTO) protein, an m6A demethylase, which led to increased overall levels of RNA m6A methylation. Cyclin A2 (CCNA2) and cyclin dependent kinase 2 (CDK2) play vital roles in MCE. The m6A levels of CCNA2 and CDK2 mRNA were dramatically enhanced by EGCG. Interestingly, EGCG increased the expression of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), which recognized and decayed methylated mRNAs, resulting in decreased protein levels of CCNA2 and CDK2. As a result, MCE was blocked and adipogenesis was inhibited. FTO overexpression and YTHDF2 knockdown in 3T3-L1 cells significantly increased CCNA2 and CDK2 protein levels and ameliorated the EGCG-induced adipogenesis inhibition. Thus, m6A-dependent CCNA2 and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition. CONCLUSION: Our findings provide mechanistic insights into how m6A is involved in the EGCG regulation of adipogenesis and shed light on its anti-obesity effect. PMID- 29795462 TI - Impact of ambient air pollution on obesity: a systematic review. AB - BACKGROUND/OBJECTIVES: Over 80% of the global populations living in urban areas are exposed to air quality levels that exceed the World Health Organization limits. Air pollution may lead to unhealthy body weight through metabolic dysfunction, chronic disease onset, and disruption of regular physical activity. SUBJECTS/METHODS: A literature search was conducted in the PubMed and Web of Science for peer-reviewed articles published until September 2017 that assessed the relationship between air pollution and body weight status. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. RESULTS: Sixteen studies met the selection criteria and were included in the review. They were conducted in seven countries, including the US (n = 9), China (n = 2), Canada (n = 1), Italy (n = 1), The Netherlands (n = 1), Serbia (n = 1), and South Korea (n = 1). Half of them adopted a longitudinal study design, and the rest adopted a cross-sectional study design. Commonly examined air pollutants included PM, NO2, SO2, O3, and overall air quality index. Among a total of 66 reported associations between air pollution and body weight status, 29 (44%) found air pollution to be positively associated with body weight, 29 (44%) reported a null finding, and the remaining eight (12%) found air pollution to be negatively associated with body weight. The reported associations between air pollution and body weight status varied by sex, age group, and type of air pollutant. Three pathways hypothesized in the selected studies were through increased oxidative stress and adipose tissue inflammation, elevated risk for chronic comorbidities, and insufficient physical activity. CONCLUSIONS: Concurrent evidence regarding the impact of air pollution on body weight status remains mixed. Future studies should assess the impact of severe air pollution on obesity in developing countries, focus on a homogenous population subgroup, and elucidate the biomedical and psychosocial pathways linking air pollution to body weight. PMID- 29795460 TI - The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study. AB - BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (P int = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant. PMID- 29795463 TI - The vagus neurometabolic interface and clinical disease. AB - The nervous system both monitors and modulates body metabolism to maintain homoeostasis. In disease states such as obesity and diabetes, the neurometabolic interface is dysfunctional and contributes to clinical illness. The vagus nerve, in particular, with both sensory and motor fibres, provides an anatomical substrate for this interface. Its sensory fibres contain receptors for important circulating metabolic mediators, including leptin and cholecystokinin, and provide real-time information about these mediators to the central nervous system. In turn, efferent fibres within the vagus nerve participate in a brain gut axis to regulate metabolism. In this review, we describe these vagus nerve mediated metabolic pathways and recent clinical trials of vagus nerve stimulation for the management of obesity. These early studies suggest that neuromodulation approaches that employ electricity to tune neurometabolic circuits may represent a new tool in the clinical armamentarium directed against obesity. PMID- 29795464 TI - Gut hormone release after gastric bypass depends on the length of the biliopancreatic limb. AB - BACKGROUND/OBJECTIVES: Changes in gut hormone secretion are important for the anti-diabetic effects of bariatric surgery. Roux-en-Y gastric bypass (RYGB) with extended biliopancreatic limb (BPL) length may improve the metabolic outcomes when compared to the classical procedure. The purpose of this study was to compare the gut hormone responses to a liquid mixed meal after RYGB with one of two different BPL lengths. SUBJECTS/METHODS: Non-diabetic weight-stable individuals previously submitted to classical RYGB (n = 9; BPL length: 87.8 +/- 20.5 cm) or long BPL RYGB (n = 11; BPL length: 200 cm) underwent a liquid mixed meal tolerance test (MMTT). Blood was sampled at baseline and 15, 30, 45, 60, 90 and 120 min later for measurement of plasma glucose, enteropancreatic hormones and total bile acids (TBA). RESULTS: Plasma glucose excursion curves were similar in the two groups. The long BPL RYGB group displayed significantly higher fasting and post-prandial GLP-1 (t = 0 min, p = 0.01 and t = 45 min, p < 0.05; tAUC: 11,205 +/- 3399 vs 7889 +/- 1686 pmol/L * min, p = 0.02) and neurotensin (t = 0 min, p = 0.02; t = 45 min, p < 0.05 and t = 60 min, p < 0.01; tAUC: 18,392 +/- 7066 vs 11,437 +/- 3658 pmol/L * min, p = 0.02) levels, while responses of GIP (t = 15 min, p < 0.01), insulin and C-peptide (t = 30 min, p < 0.001) were lower as compared to classical RYGB. There were no differences in glucagon, PP, PYY and TBA between the groups. CONCLUSIONS: RYGB with a longer BPL results in a distinctive post-prandial hormone profile with augmented GLP-1 and neurotensin responses that could be beneficial for the metabolic outcomes of the surgery. PMID- 29795466 TI - Upregulation of angiostatic chemokines IP-10/CXCL10 and I-TAC/CXCL11 in human obesity and their implication for adipose tissue angiogenesis. AB - BACKGROUND/AIMS: Impaired angiogenesis is linked to adipose tissue (AT) dysfunction, inflammation, and insulin resistance in human obesity. Chemokine (C X-C motif) receptor. (CXCR3) ligands are important regulators of angiogenesis in different disease contexts such as cancer; however, their role in human morbid obesity is unknown. We investigated the role of the CXCR3 axis in AT angiogenesis in morbidly obese patients. SUBJECTS/METHODS: The study group comprised 50 morbidly obese patients (mean age 44 +/- 1 years, body mass index 44 +/- 1 kg/m2) who had undergone laparoscopic Roux-Y-gastric bypass surgery, and 25 age-matched non-obese control subjects. We measured the circulating levels of the CXCR3 ligands monokine induced by interferon-gamma (MIG/CXCL9), interferon-gamma inducible protein 10 (IP-10/CXCL10), and interferon-gamma-inducible T-cell alpha chemoattractant (I-TAC/CXCL11) in all studied subjects. Additionally, the expression of CXCR3 ligands was analyzed in paired biopsies of subcutaneous and visceral AT obtained during the laparoscopic procedure in morbidly obese patients. Additionally, we explored the functional role of CXCR3 ligands on angiogenesis in AT from morbidly obese patients using an ex vivo assay. RESULTS: Plasma levels of CXCL10 and CXCL11 were significantly higher in morbidly obese patients than in controls (p < 0.01). In ex vivo assays, angiogenic growth was markedly lower in visceral AT than in subcutaneous AT (p < 0.05), which was related to significant tissue upregulation of CXCL10, CXCL11 and CXCR3 (p < 0.05). CXCL10 or CXCL11 inhibited AT angiogenesis (p < 0.05), and blockade of CXCR3 function significantly increased capillary sprouting in visceral fat deposits (p < 0.05). Western blot analysis showed that the p38 mitogen-activated protein kinase signaling pathway was implicated in the angiostatic effects of CXCR3 in AT. CONCLUSIONS: CXCL10 and CXCL11 may play. deleterious role in obesity as potential inhibitors of AT angiogenesis. Accordingly, pharmacological blockade of CXCR3 could represent. therapy to prevent AT dysfunction in obesity. PMID- 29795465 TI - Paternal cholestasis exacerbates obesity-associated hypertension in male offspring but is prevented by paternal ursodeoxycholic acid treatment. AB - BACKGROUND: Obesity is a heterogeneous phenotype and risk associations to non communicable diseases such as cardiovascular disease and type 2 diabetes are influenced by several factors. The paternal metabolic status at the time of conception influences offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease. Cholestatic liver diseases are characterized by raised circulating serum bile acid levels and dyslipidemia, and are commonly treated with ursodeoxycholic acid (UDCA). We hypothesized that paternal cholestasis alters offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease and that this may be modified by paternal UDCA treatment. METHODS: Cholestasis was induced in male C57BL/6 mice with a 0.5% cholic acid (CA)-supplemented diet for 10 weeks prior to mating with normal chow (NC)-fed females. Offspring of cholestatic and NC-fed fathers were fed either a NC diet or challenged with an obesogenic 'western diet' (WD) from 12 weeks of age. Offspring body weight and cardiometabolic function were assessed, and the impact of treatment of paternal cholestasis with UDCA was evaluated. RESULTS: Male offspring (18 weeks old) of cholestatic fathers challenged with WD had raised fasting insulin, hepatic triglyceride content and serum cholesterol levels compared to diet-matched controls. At 25-29 weeks of age, WD-fed male offspring of cholestatic fathers had higher systolic and diastolic blood pressure than controls and this was prevented by paternal UDCA treatment. In contrast, WD challenged female offspring of cholestatic fathers showed improved glucose tolerance compared to controls. CONCLUSIONS: We demonstrated in our model of paternal cholestasis that offspring susceptibility to adiposity-associated cardiometabolic disease is affected in a sex-specific manner and paternal UDCA treatment had a protective effect against hypertension in the obese male offspring. The most prevalent human cholestatic conditions are primary sclerosing cholangitis and primary biliary cholangitis. These findings are of clinical relevance to children of men with these conditions. PMID- 29795468 TI - The case of GWAS of obesity: does body weight control play by the rules? AB - As yet, genome-wide association studies (GWAS) have not added much to our understanding of the mechanisms of body weight control and of the etiology of obesity. This shortcoming is widely attributed to the complexity of the issues. The appeal of this explanation notwithstanding, we surmise that (i) an oversimplification of the phenotype (namely by the use of crude anthropometric traits) and (ii) a lack of sound concepts of body weight control and, thus, a lack of a clear research focus have impeded better insights most. The idea of searching for polygenetic mechanisms underlying common forms of obesity was born out of the impressive findings made for monogenetic forms of extreme obesity. In the case of common obesity, however, observational studies on normal weight and overweight subjects never provided any strong evidence for a tight internal control of body weight. In addition, empirical studies of weight changes in normal weight and overweight subjects revealed an intra-individual variance that was similar to inter-individual variance suggesting the absence of tight control of body weight. Not least, this lack of coerciveness is reflected by the present obesity epidemic. Finally, data on detailed body composition highlight that body weight is too heterogeneous a phenotype to be controlled as a single entity. In summary GWAS of obesity using crude anthropometric traits have likely been misled by popular heritability estimates that may have been inflated in the first place. To facilitate more robust and useful insights into the mechanisms of internal control of human body weight and, consequently, the genetic basis of obesity, we argue in favor of a broad discussion between scientists from the areas of integrative physiologic and of genomics. This discussion should aim at better conceived studies employing biologically more meaningful phenotypes based on in depth body composition analysis. To advance the scientific community-including the editors of our top journals-needs a re-launch of future GWAS of obesity. PMID- 29795467 TI - Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects. AB - Obesity increases risk of falling, but the effect of bariatric surgery on fall related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was >= 34 kg/m2 in men and >=38 kg/m2 in women. The surgery per-protocol group (n = 2007) underwent gastric bypass (n = 266), banding (n = 376), or vertical banded gastroplasty (n = 1365), and controls (n = 2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07 1.36; P = 0.002). The incidence differed between treatment groups (P < 0.001, log rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P < 0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment. PMID- 29795469 TI - Are BMI and inflammatory markers independently associated with physical fatigability in old age? AB - BACKGROUND: Obesity and chronic low-grade inflammation have both been implicated in the onset of physical fatigue. However, few studies have investigated the independence of these associations in older community-dwelling populations. We therefore aimed to investigate the associations of body mass index (BMI) and inflammatory markers at age 60-64 with perceived physical fatigability at age 68 and to assess whether any such associations were independent of each other and potential confounding factors. A secondary aim was to investigate whether any association with BMI extended back into earlier adulthood. METHODS: Participants of the MRC National Survey of Health and Development (N = 1580) had BMI and levels of interleukin-6 (IL-6) and C-reactive protein (CRP) measured during clinical assessments at age 60-64. These were related to self-perceived physical fatigability assessed at age 68 using the Pittsburgh Fatigability Scale (PFS) (total score:0 (no physical fatigue)-50 (extreme physical fatigue)). RESUTS: Women had higher mean PFS scores than men (mean (SD): 16.0 (9.1) vs 13.2 (8.9), p < 0.01). In sex-adjusted models, BMI, CRP and IL-6 were each associated with PFS scores. When all three factors were included in the same model, BMI and IL-6 remained associated with PFS scores whereas CRP did not. After adjustment for a range of potential confounders, associations of BMI and IL-6 with PFS scores were still evident; fully adjusted differences in mean PFS score = 3.41 (95% CI: 0.59, 6.24) and 1.65 (0.46, 2.84) for underweight and obese participants when compared with normal weight and, 2.78 (1.65, 3.91) when comparing those with an IL-6 of 2.51-8.49 pg/mL with levels <1.50. CONCLUSIONS: BMI and inflammation may both be suitable targets for intervention to reduce the burden of physical fatigability in later life. Further, interventions that target both obesity and elevated levels of IL-6 are likely to be more effective than those focusing on only one. PMID- 29795470 TI - The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery. AB - Neurotensin is a peptide with effects on appetite and intestinal lipid absorption. Experimental data suggest a role in glucose homeostasis, while human data is missing. Here, 20 morbidly obese subjects either underwent biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB) in a randomized fashion. Before and 1 year after surgery, anthropometric data, body composition, clinical biochemistry, insulin sensitivity by means of euglycemic hyperinsulinemic clamps (HEC) and fasting plasma proneurotensin 1-117 were analyzed. Plasma proneurotensin increased significantly more 1 year after BDP than RYGB (P = 0.028), while weight loss was comparable. After metabolic surgery, proneurotensin correlated positively with insulin sensitivity (M-value) (r = 0.55, P < 0.001), while an inverse relationship with fasting glucose, HOMA IR and HbA1c was observed (P < 0.05 for all components). After adjustment for age and gender, proneurotensin and BMI remained independently related with delta of M value (beta = 0.46 and beta = 0.51, P < 0.05, resp.). From these data we conclude that proneurotensin positively correlates with insulin sensitivity uniquely after weight loss induced by metabolic surgery in humans. BDP leads to a stronger increase in the anorexigenic peptide compared to RYGB. PMID- 29795471 TI - Early weight loss outcomes from a newly established hospital-affiliated specialized obesity care delivery model in Central Florida. AB - SIGNIFICANCE: We evaluated weight loss outcomes in a newly established hospital affiliated, physician-directed multidisciplinary, and personalized obesity care model. METHODS: Fifty established patients in a specialized obesity medicine practice underwent intensive lifestyle intervention +/-adjunctive pharmacotherapy (46/50) for >6 consecutive months and when required, psychological intervention. We identified demographics, obesity-related comorbidities, anthropometric changes over time, and laboratory screen. Psychosocial status was determined using Beck Depression Inventory-II (BDI-II), Brownell-Stunkard Weight-Loss Readiness Test, and Impact of Weight on Quality of Life-Lite (IWQOL). RESULTS: Patient characteristics (mean +/- SD) were: 70% female; age 47.0 +/- 16.4 y; weight 111.55 +/- 32.8 kg; BMI 39.3 +/- 8.8 kg/m2; % body fat 45.5 +/- 6.3. Patients had attempted at least one diet prior to seeking tertiary obesity care and averaged 2.5 major co-morbidities. In regards to health status, 74% were insulin resistant [HOMA]; 12% had Type 2 DM (HbA1c > 6.5%); 46% were hypertensive; 48% had dyslipidemia, 38% were vitamin D deficient; 44% were depressed (BDI-II). Weight loss at 3 and 6 months averaged -4.18 and -7.88 kg and percentage changes in BMI a respective -4.39 and -7.74% (p < 0.0001). Forty percentage were early responders (ER), having lost >= 5% of their initial weight 3 months into the program. Total weight loss for ER vs. non-responders (NR) at 3 months was -7.90 and -1.71 kg, respectively (p < 0.0001) and mean % BMI changes from baseline were a respective -7.77 and -1.88%. CONCLUSIONS: Organized hospital-affiliated specialized obesity care delivery models can be successful in personalized obesity treatment. These types of medical programs for complicated obesity are likely to reduce impediments to addressing obesity effectively. PMID- 29795472 TI - Maternal obesity aggravates the abnormality of porcine placenta by increasing N6 methyladenosine. AB - BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m6A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. SUBJECTS/METHODS: Forty four placentas from eight sows (backfat thickness >=21 mm) were divided into four groups by piglet weight, with group1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m6A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m6A modification in the key genes. RESULTS: Compared with the comparative groups, the expression levels of PPARgamma, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m6A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m6A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m6A. By using MeRIP-QPCR technology, the m6A modification in PPARgamma, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. CONCLUSION: We infer that in maternity obesity, the higher m6A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m6A demethylase FTO. PMID- 29795473 TI - Reply to "Between SCA5 and SCAR14: delineation of the SPTBN2 p.R480W-associated phenotype" by Nuovo et al. PMID- 29795474 TI - Between SCA5 and SCAR14: delineation of the SPTBN2 p.R480W-associated phenotype. PMID- 29795475 TI - Economic evaluation of genomic sequencing in the paediatric population: a critical review. AB - Systematic evidence is critical to the formulation of national health policy to provide public funding for the integration of genomic sequencing into routine clinical care. The purpose of this review is to present systematic evidence on the economic evaluation of genomic sequencing conducted for paediatric patients in clinical care, and to identify any gaps in the methodology of economic evaluations. We undertook a critical review of the empirical evidence from economic evaluations of genomic sequencing among paediatric patients searching five electronic databases. Our inclusion criteria were limited to literature published in the English language between 2010 and 2017 in OECD countries. Articles that met our inclusion criteria were assessed using a recognised checklist for a well-designed economic evaluation. We found 11 full-text articles that met our inclusion criteria. Our analysis found that genomic sequencing markedly increased the diagnostic rate to 16-79%, but lowered the cost by 11-64% compared to the standard diagnostic pathway. Only five recent studies in paediatric clinical cohorts met most of the criteria for a well-designed economic evaluation and demonstrated cost-effectiveness of genomic sequencing in paediatric clinical cohorts of patients. Our review identified the need for improvement in the rigour of the methodologies used to provide robust evidence for the formulation of health policy on public funding to integrate genomic sequencing into routine clinical care. Nonetheless, there is emerging evidence of the cost-effectiveness of genomic sequencing over usual care for paediatric patients. PMID- 29795476 TI - A recurrent de novo CUX2 missense variant associated with intellectual disability, seizures, and autism spectrum disorder. AB - In most patients with intellectual disability (ID), the etiology is unknown, but lately several de novo variants have been associated with ID. One of the involved genes, CUX2, has twice been reported to be affected by a de novo variant c.1768G>A; p.(Glu590Lys) in patients with ID or epileptic encephalopathy. CUX2 is expressed primarily in nervous tissues where it may act as a transcription factor involved in neural specification. Here we describe a third case who was diagnosed with epilepsy including general and myoclonic seizures, moderate to severe cognitive disability, and infantile autism. The patient was heterozygous for the c.1768G>A; p.(Glu590Lys) variant in CUX2 identified by whole exome sequencing. These findings strongly suggest a causal impact of this variant and add to our understanding of a subset of patients with ID, seizures, and autism spectrum disorder as well as suggest an important role for the CUX2 gene in human brain function. PMID- 29795477 TI - The global landscape of cancer cell therapy. PMID- 29795478 TI - Comparison of glycopyrronium versus tiotropium on the time to clinically important deteriorations in patients with COPD: a post-hoc analysis of randomized trials. AB - Glycopyrronium is a once-daily, inhaled long-acting muscarinic antagonist (LAMA) demonstrating similar efficacy to inhaled tiotropium in patients with moderate-to severe COPD; however, the benefit of LAMAs on COPD symptoms has been variable. COPD is a progressive disease in which many patients develop an acute or sustained deterioration. Data on the prevention of clinically important deteriorations (CID) using LAMAs are limited. A pooled analysis was performed on four Phase III trials (n = 2936) that compared the efficacy of glycopyrronium (n = 1859) with tiotropium (n = 1077). The primary endpoint was significant delay and/or reduction in the occurrence of CID. CID was defined as any of the following: >=100 mL decrease from baseline in pre-dose forced expiratory volume in 1 second (FEV1), >=4 point increase in St George's Respiratory Questionnaire score or a moderate-to-severe COPD exacerbation occurring after the first dose of study medication. A sustained CID was a CID occurring on >=2 consecutive visits 4 weeks apart or for >=50% of all available subsequent visits. Baseline characteristics for the overall population were similar. Patients had moderate (62%) or severe (38%) COPD. Mean post-bronchodilator FEV1 was approximately 55% predicted, and mean FEV1 reversibility was 16.7 and 18.6% in the glycopyrronium and tiotropium groups, respectively. Both glycopyrronium and tiotropium significantly reduced time to CID and sustained CID versus placebo (p < 0.001). No statistically significant differences were found between the glycopyrronium and tiotropium treatment groups in time to CID or sustained CID. Glycopyrronium is effective in delaying time to clinically important deteriorations, with similar efficacy to tiotropium. PMID- 29795480 TI - Become a part of the Carriere Philosophy in orthodontics. PMID- 29795481 TI - New scanners featuring greater power and speed. PMID- 29795482 TI - Charity launches National Smile Month 2018. PMID- 29795479 TI - Role of Kupffer cells in the progression of CRC liver metastases after the first stage of ALPPS. AB - Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-alpha and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs). Interestingly, KCs expressed COX-2 (M1 polarization), while TAMs expressed mainly arginase-1 (M2 polarization). ALPPS also induced a decrease of tumor-infiltrating lymphocytes and an increase of intrahepatic T lymphocytes. Thus, ALPPS technique seems to induce a hypoxic environment, which enhances hepatic HIF1-alpha and VEGF expression and may promote KCs and TAMs polarization. Consequently, the regenerative stimulus seems to be driven by a pro-inflammatory and hypoxic environment, in which M1 intrahepatic macrophages expressing COX-2 and T Lymphocytes play a key role, facts which may be related with the tumor progression observed. PMID- 29795483 TI - The BDJ's environment. PMID- 29795484 TI - FDI guide addresses the global burden of periodontal disease. PMID- 29795485 TI - Assessment of public and professional perceptions of access to unscheduled dental care. PMID- 29795488 TI - Over 300,000 dentists participate in clinical education. PMID- 29795486 TI - National clinical guidelines for the management of unerupted maxillary incisors in children. AB - This article summarises recently updated guidelines produced by the Clinical Governance Directorate of the British Orthodontic Society through the Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England (FDSRCS) on the management of unerupted maxillary incisor teeth in children. The maxillary incisor teeth usually erupt in the early mixed dentition but eruption disturbances can occur and are often attributable to local factors. A failure of eruption will affect the developing occlusion and potentially influence psychological development of the child. The general principles of management for delayed eruption or impaction of these teeth is to ensure that adequate space exists in the dental arch and to remove any obstruction to eruption. Consideration should also be given to further promoting eruption through surgical exposure of the incisor, with or without subsequent orthodontic traction. A number of factors influence the decision-making process, including patient age, medical history, potential compliance, aetiology and position of the unerupted incisor. Treatment planning should be complemented by careful clinical assessment and the use of appropriate special investigations. To optimise the treatment outcome a multidisciplinary specialist approach is recommended. PMID- 29795487 TI - Carotid aneurysms: unusual referrals from general dental practice. AB - Oral and maxillofacial surgeons carry out the diagnosis and treatment of diseases affecting the mouth, jaws, face and neck. They provide a critical referral service for dentists in general practice, with the most suspicious of these being sent as 'urgent suspected cancer', or 'USC'. According to national guidelines, such cases must be seen within 14 days. In January and February 2017, the oral and maxillofacial team in Morriston hospital received two such referrals from separate GDPs in the locality. Both were prioritised and seen within the two week window on consultant clinics. These two cases presented as enlarging, firm and painful neck swellings in otherwise relatively healthy adults, with no classical risk factors for malignancy, such as smoking, high alcohol intake or HPV virus. There was no dental pathology noted in either. Following clinical examination and special investigations within the OMFS department in Morriston Hospital, both patients were diagnosed, and treated under the vascular surgical team via surgical repair for carotid aneurysms. This is a condition rarely considered by dentists, and an uncommon differential diagnosis of a neck lump. PMID- 29795489 TI - Orthodontics: Making false promises. PMID- 29795490 TI - Longevity of anterior resin bonded bridges: Survival rates of two tooth preparation designs. AB - Anterior resin bonded bridges with described tooth preparation designs demonstrate a high survival rate. PMID- 29795491 TI - Feeling protective. PMID- 29795492 TI - Never events: Recent update. PMID- 29795493 TI - Editorial decisions: Cover art defended. PMID- 29795494 TI - Cause for concern: BDA v GDC. AB - In this Opinion article I will discuss the relationship between the BDA and the GDC, the nature of the BDA's and dentists' language when communicating with the GDC and when discussing the GDC in public forums, such as this journal. I also suggest ways this relationship can be improved for the benefit of dentists and the GDC. PMID- 29795496 TI - Study supports efficacy of collagen membrane. PMID- 29795497 TI - Dentists on film: Blue Jasmine. PMID- 29795495 TI - Longevity of ceramic onlays: A systematic review. AB - The most common pattern of failure is fracture of the ceramic material and the risk of failure seems to increase if the restored tooth is non-vital and the patient demonstrates parafunctional habits. PMID- 29795499 TI - Essential orthodontics. PMID- 29795498 TI - Restorations in primary teeth: a systematic review on survival and reasons for failures. AB - The most common reason for failure of restorations in primary teeth is secondary caries. PMID- 29795500 TI - The record and delivery of caries prevention for children in a primary care setting: a multi-practice collaborative clinical audit. PMID- 29795501 TI - Last chance for bursary awards. PMID- 29795502 TI - Young dentists: breaking the silence. AB - Now is the time for young dentists to voice their concerns - to ensure policy makers understand problems faced by the dental workforce of tomorrow. This opinion article highlights the pertinent factors which have reduced young dentists to provide defensive dentistry provided in a far from ideal NHS environment. PMID- 29795504 TI - A titan among tongue cleansers. PMID- 29795503 TI - 32 and you - genetic testing for dental disorders. AB - Genetic testing for serious illness and disease is becoming increasingly embedded in NHS healthcare. It can confirm a clinical diagnosis or guide therapy. Genetic testing for dental developmental disorders has moved beyond the realms of rarified grant-funded research groups and is now sufficiently rapid and affordable to be offered as part of a clinical service in some dental teaching hospitals. The first presentation of some genetic diseases may be in the dental surgery, so the family dentist should hone their diagnostic skills to identify patients who would benefit from referral to a genetics service. While diagnosis may sometimes guide treatment, there are now examples where it can even lead to cure. This article aims to describe some concepts and issues that a dentist should consider when referring for testing for a genetic dental disorder, and proposes that this subject area should be expanded in the dental undergraduate and postgraduate curricula in the UK. PMID- 29795506 TI - Engaging patients to improve communication and comprehension. PMID- 29795505 TI - Root caries: From prevalence to therapy. PMID- 29795507 TI - Film: Dentist's film shown at Cannes. PMID- 29795508 TI - Be a wizard with your wand. PMID- 29795509 TI - Guidelines relevant to paediatric dentistry - do foundation dentists and general dental practitioners follow them? Part 2: Treatment and recall. PMID- 29795510 TI - New Flexible Payment Plans for member and non-member dentists. PMID- 29795512 TI - Martin Hobdell. PMID- 29795511 TI - Oral health: Learning styles. PMID- 29795513 TI - New survey reveals lack of knowledge about enamel erosion. PMID- 29795514 TI - BDA North Western Branch AGM Notice. PMID- 29795515 TI - Partnership to protect those First Smiles. PMID- 29795516 TI - You're on camera. PMID- 29795517 TI - Influence of different implant geometry in clinical longevity and maintenance of marginal bone: a systematic review. AB - Implant geometry seems to have little influence on marginal bone loss, survival and success rates. PMID- 29795519 TI - An ideal alternative to explore. PMID- 29795518 TI - The ultimate guide to restoration longevity in England and Wales. Part 2: Amalgam restorations - time to next intervention and to extraction of the restored tooth. PMID- 29795520 TI - Activity of DNA-targeted C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates against aerobically and hypoxically grown Mycobacterium tuberculosis under acidic and neutral conditions. AB - Mycobacterium tuberculosis (Mtb) is the aetiological agent of tuberculosis, the leading cause of death worldwide from a single infectious agent. Mtb is a highly adaptable human pathogen that might enter a dormant non-replicating (NR), drug tolerant stage. Reactivation of dormant Mtb can lead to active disease. Antibiotic treatments of active and latent tuberculosis are long, complex and may fail to fully eradicate the infection. Therefore, it is imperative to identify novel compounds with new mechanisms of action active against NR bacilli. Dormant Mtb habitat is mostly thought to be the pH-neutral and hypoxic caseous granuloma. We have used the Wayne culture model to reproduce this environment and tested the activities of two DNA-targeted agents, C8-linked-pyrrolobenzodiazepine(PBD) polyamide conjugates 1 and 2, against Mtb grown in aerobic and hypoxic conditions in both acidic and pH-neutral media. PBD 2 showed growth inhibitory activity at 5.1 ug/ml against 19-day-old hypoxic NR Mtb cultures with 1.8 log10 CFU reduction on day 21 at pH 7.3. PBD 2 was particularly effective against 5-day-old aerobic cells at pH 7.3, with CFU reduction (>6.8 log10) on day 21 at 5.1 ug/ml being identical to that of rifampin at 8 ug/ml. PBD 2 qualifies as a promising lead against aerobic and NR Mtb. PMID- 29795521 TI - Drug information, misinformation, and disinformation on social media: a content analysis study. AB - Dissemination of misleading drug information through social media can be detrimental to the health of the public. This study, carried out in Bahrain, evaluated the truthfulness of 22 social media claims about drugs (72.7%), dietary supplements (22.7%), and toxic bisphenol-A (4.5%). They circulated on WhatsApp platform, as case studies. We categorized claims as objectively true, false, or potentially misleading. The content analysis revealed that "potentially misleading" claims were the most frequent messages (59.1%). They tend to exaggerate the efficacy or safety without sufficient evidence to substantiate claims. False claims (27.3%) were likely due to unfair competition or deception. Overall, 13.6% of the messages were objectively true claims that could withstand regulatory scrutiny. Majority of the drug-related messages on social media were potentially misleading or false claims that lacked credible evidence to support them. In the public interest, regulatory authorities should monitor such information disseminated via social media platforms. PMID- 29795522 TI - Public health actions to mitigate long-term consequences of child maltreatment. AB - Child maltreatment (CM) is highly prevalent and one of the most injurious conditions that children may experience. Because it is often-clandestine, it is difficult to assure that existing prevention and treatment mechanisms reach those in need. CM's consequences may take a long time to be recognized and expressed. We discuss the need to increase public health actions when the person reaches adulthood to mitigate the consequences of CM. We propose three intervention targets to alleviate CM-related difficulties in adults: emotion regulation, social functioning, and self-concept. By enhancing awareness and facilitating access to these interventions and using technology-based strategies, we expect this approach to benefit affected persons. It may also reduce the risk for transmission of CM consequences across generations. PMID- 29795524 TI - Before reproducibility must come preproducibility. PMID- 29795526 TI - An improved assembly and annotation of the melon (Cucumis melo L.) reference genome. AB - We report an improved assembly (v3.6.1) of the melon (Cucumis melo L.) genome and a new genome annotation (v4.0). The optical mapping approach allowed correcting the order and the orientation of 21 previous scaffolds and permitted to correctly define the gap-size extension along the 12 pseudomolecules. A new comprehensive annotation was also built in order to update the previous annotation v3.5.1, released more than six years ago. Using an integrative annotation pipeline, based on exhaustive RNA-Seq collections and ad-hoc transposable element annotation, we identified 29,980 protein-coding loci. Compared to the previous version, the v4.0 annotation improved gene models in terms of completeness of gene structure, UTR regions definition, intron-exon junctions and reduction of fragmented genes. More than 8,000 new genes were identified, one third of them being well supported by RNA-Seq data. To make all the new resources easily exploitable and completely available for the scientific community, a redesigned Melonomics genomic platform was released at http://melonomics.net . The resources produced in this work considerably increase the reliability of the melon genome assembly and resolution of the gene models paving the way for further studies in melon and related species. PMID- 29795527 TI - Low dose daily versus on-demand high dose tadalafil in diabetic patients with erectile and ejaculatory dysfunction. AB - The aim was to compare the differences between daily 5 mg and on-demand 20 mg tadalafil use in diabetic patients with erectile dysfunction (ED), and the effects of two different tadalafil protocols on ejaculatory and lower urinary tract symptoms (LUTS). Of the 63 diabetic patients with ED, 31 were given 5 mg tadalafil once a day, and 32 were given 20 mg tadalafil on-demand four times a month over three months. Erectile function, erectile hardness, ejaculatory function, and LUTS were assessed at pretreatment, first- and third-month controls. Both tadalafil protocols increased International Index of Erectile Function (IIEF) scores in all patients under 65 years, whereas patients older than 65 years did not benefit. Ejaculatory function, the quality of the hardness of an erection, and LUTS improved in both groups in the study. Tadalafil improved sexual function with acceptable side effects in diabetic men with ED. Both protocols equally improved LUTS and the quality of the erection. Daily use of 5 mg of tadalafil significantly improved the quality of ejaculation and LUTS more than the on-demand use of 20 mg of tadalafil. It may be beneficial to give 5 mg tadalafil daily to patients over 65 years old who do not benefit from treatment with 20 mg of tadalafil or in patients who have LUTS over 65 years old. PMID- 29795528 TI - Association between obstructive sleep apnea and erectile dysfunction: a systematic review and meta-analysis. AB - The purpose of the present systematic review and meta-analysis was to assess the association between obstructive sleep apnea (OSA) and erectile dysfunction (ED). To address the focused question, "Is there an association between OSA and ED?" indexed databases were searched up to May 2017 without time or language restrictions using various key words including: obstructive sleep apnea, sleep apnea syndromes, erectile dysfunction, sleep-disordered breathing, snoring, sexual function, and impotence. Review articles, case-reports and case-series, commentaries, letters to the editor, interviews and updates, studies assessing the efficacy of OSA treatment in the improvement of ED, or studies evaluating the efficacy of ED treatment in the improvement of OSA were excluded. Twenty-eight observational studies were included for qualitative synthesis. Overall, 19 studies had a cross-sectional design, 7 studies were case-control, and 2 were cohort studies. The odds ratios (OR) with a 95% confidence interval were calculated from 10 studies. The combined OR was 0.45, with a 95% confidence interval of 0.18-0.71, indicating that in patients without OSA, the risk of ED is significantly lower compared with patients with OSA. The available evidence shows that OSA is associated with a higher risk of ED; however, further well-designed controlled clinical trials and longitudinal prospective studies are needed in this regard. PMID- 29795529 TI - Infection risk of undergoing multiple penile prostheses: an analysis of referred patient surgical histories. AB - Inflatable penile prosthesis (IPP) is the gold standard for medically refractory erectile dysfunction. Infectious complications remain a significant concern in IPP revision surgery. We sought to evaluate the impact of number of IPP surgeries on subsequent infection rates. A retrospective analysis was performed on all new patients (self or outside provider referred) presenting for consideration of IPP revision or salvage surgery between 2013 and 2015. Histories were reviewed including number of prior IPPs, reason for evaluation, and rate, number, and timing of prior IPP infections. No patients were operated on by the primary investigator prior to data acquisition. We identified 44 patients with at least one prior IPP presenting for consultation regarding IPP revision/salvage. There were 88 IPPs placed by 28 different surgeons. In patients with two or more devices, 55% had at least two different surgeons. The most common reason for presentation was malfunction (52%). The risk of specific device infection was strongly correlated and increased based on number of prior IPPs: 1st (6.8%; 3/44), 2nd (18.2%; 4/22), 3rd (33.3%; 4/12), 4th (50%; 4/8), and 5th (100%; 2/2) (R2 = 0.90, p = 0.01). Similarly, overall rates of infection positively correlated with number of prior IPP-related surgeries performed (R2 = 0.97, p < 0.01). The median time to development of infection after most recent IPP surgery was 2 months (IQR 1-3.3 months). Infection rates of revision/salvage IPP surgery increase with each subsequent IPP placement or following IPP-related surgeries. The majority of patients referred for penile implant surgery can expect to have experienced at least one infection by their 4th device. These data represent a change in paradigm on revision prosthetic surgery. PMID- 29795525 TI - The association of VDR polymorphisms and type 2 diabetes in older people living in community in Santiago de Chile. AB - INTRODUCTION: Several polymorphisms have been associated with obesity and type 2 diabetes in different populations. OBJECTIVE: To investigate the frequencies of a genetic polymorphism of vitamin D receptor (FokI and BsmI) in patients with T2D. METHODS: The case-control study was conducted in 138 patients with T2D and 172 control subjects, men and women (60-79 years old). The genotype and allele frequency determination of VDR polymorphisms were determined in these subjects. RESULTS: The frequency of the C allele of the FokI polymorphism was significantly higher in the T2D group than in healthy subjects (p = 0.025). The frequencies of the BsmI variant were similar in subjects with and without T2D (p = 0.747). Consistent with these data, there was an association of the C allele with T2D (OR = 1.74, 95% CI = 1.003-3.084, p = 0.036), but not the AG + GG variants for BsmI (OR = 1.02, 95% CI = 0.635-1.649, p = 0.916). We can observe a significant association between carrier of the T > C variant of FokI and type 2 diabetes, adjusted for vitamin D, age, obesity (overweight and obesity), seasonality, sex and Homa-IR. Here, we show a significant association between the FokI polymorphisms (TC + CC) and T2D with an odds ratio of 1.9001 (95% CI (1.0970 3.6838), p = 0.041). CONCLUSION: Our study suggests that the C allele (TC + CC) of the VDR-FokI gene is a possible risk factor for T2D in older people living in a community in Santiago de Chile. PMID- 29795530 TI - The relationship between penile deformity, age, psychological bother, and erectile dysfunction in a sample of men with Peyronie's Disease (PD). AB - The aim of the present study was to investigate which PD specific factors (e.g., degree of penile curvature, levels of pain) cause most distress and to further explore whether there are specific subgroups of patients that report particularly high levels of psychological distress. Data were available for N = 119 men with a clinical diagnosis of PD presenting at a private Uro-Andrology in Germany. The strongest complaint of men with PD was being bothered by the look of the penis as opposed to being distressed by the pain (3.48 vs. 2.11). 75.4% reported having significantly less intercourse due to PD and for 61.4% this was very bothersome. Plaque size correlated positively with the level of symptom bother (r = 0.73, p < 0.05). Furthermore, men with a stronger curvature reported more concerns regarding size and form of the penis (r = 0.18, p < 0.05), more overall sexual dissatisfaction (r = -0.38, p < 0.001), and more PD related psychological and physiological symptoms (r = 0.58, p < 0.001). 44.4% of patients had a concurrent ED. Highest level of symptom bother was reported by men with a a strong curvature and a comorbid ED. Clinicians should pay special attention to patients presenting with extreme penile deformity and impaired sexual functioning, as they show the highest levels of psychological distress. Here, additional psychosexual support might be necessary. PMID- 29795531 TI - Patient's choice of health information and treatment modality for Peyronie's disease: a long-term assessment. AB - Despite various Peyronie's disease (PD) treatment options, the literature is sparse regarding patient preference for available therapies. Our data explore resource and treatment choices made by PD men following diagnosis. A survey was mailed to 719 randomly selected PD men evaluated at our institution from 1990 2012. Questions included evaluation of treatments and preferred information resources. Results were summarized as a descriptive report with statistical analyses performed as indicated. A total of 162 men (median age 65) responded with median PD duration of 9.2 years. Information sources included medical websites (38.9%), physician (35.8%), and books (<1%). Overall, patients felt 72.5% (SD = 40) of physicians had a good understanding of PD. About 53.1% of men had tried at least one therapy with 37.2% trying two or more. In comparing therapies, most surgical patients reported improvement at 82.8%. Among a cohort of PD men responding to a mailed survey, medical websites were the most widely used source of information. Almost half of the patients chose not to pursue any form of therapy, while the remaining majority elected for non-operative intervention. These results suggest a need for greater patient and provider education on PD management. PMID- 29795532 TI - Effect of operative local anesthesia on postoperative pain outcomes of inflatable penile prosthesis: prospective comparison of two medications. AB - Few studies have examined the roles of dorsal penile nerve block (DPNB) and penile ring block (PRB) in surgery of inflatable penile prosthesis (IPP) placement. We sought to compare the postoperative pain outcomes of two different medications used in DPNB plus PRB. We thus carried out a prospective study of patients with erectile dysfunction who underwent "de novo" IPP placement between January 2013 and June 2013. Patients were divided to one of three groups: 1-DPNB plus PRB with bupivacaine injection; 2-DPNB plus PRB with ropivacaine injection and, 3-Control group without DPNB or PRB injection. Postoperative pain score and pain medication usage were recorded 2 h postoperatively, and every 24 h, for a week. The Visual Analog Scale (VAS) was used as pain scale measurement. A total of 131 patients were included in this study: 40 to bupivacaine, 47 to ropivacaine, and the rest were controls. Two hours postoperatively, mean VAS was significantly different (p < 0.0001) between medicated patients and the control group, however, no significant differences were observed between medication groups. Mean VAS was not significantly different among the groups from post surgical day 2 thru 7. In conclusion, DPNB plus PRB during IPP provided effective analgesia in the immediate post-operative recovery. PMID- 29795533 TI - Prenatal n-3 long-chain fatty acid status and offspring metabolic health in early and mid-childhood: results from Project Viva. AB - Higher maternal and biomarker levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been associated with improved perinatal outcomes and may also influence offspring metabolic health. Past studies were not powered to examine metabolic outcomes and few have specifically targeted metabolically vulnerable populations. We examined the associations of prenatal n-3 LCPUFA status with markers of metabolic health in early and mid-childhood in the full population as well as stratified by maternal glucose tolerance. Our data consisted of 1418 mother-child dyads from Project Viva, a longitudinal, prospective pre-birth cohort enrolled in eastern Massachusetts. We assessed maternal dietary intake of fish and n-3 LCPUFA in mid-pregnancy using a validated food frequency questionnaire. N-3 LCPUFA levels were quantified in maternal second trimester and umbilical cord plasma using liquid-gas chromatography. We assessed offspring anthropometry, adiposity, and blood pressure at early (median age: 3.2 years) and mid-childhood (median age: 7.7 years); and assayed blood samples collected at these visits for metabolic biomarkers. We report here multivariable effect estimates and 95% CI. Early childhood BMI z-score was on average 0.46 (1.03) units and waist circumference 51.3 (3.7) cm. At mid-childhood these measures were 0.39 (1.00) units and 60.0 (8.3) cm, respectively. Higher cord plasma DHA levels were associated with lower BMI z-score ((Q)uartile 4 vs. Q1: -0.21, 95% CI: -0.38, -0.03), waist circumference (Q4 vs. Q1: -0.63, 95% CI: 1.27, 0.00 cm), and leptin levels (Q4 vs. Q1: -0.36, 95% CI: -0.77, 0.05 ng/mL) in early childhood. These associations were strongest and reached significance in offspring of women with isolated hyperglycemia vs. better or worse glycemic status. Higher maternal DHA + EPA (Q4 vs. Q1: -1.59, 95% CI: -2.80, -0.38 MUg/mL) and fish (>=3 vs. 0 portions/week: -2.18, 95% CI: -3.90, -0.47 MUg/mL) intake was related to lower adiponectin in early childhood. None of these associations persisted with mid-childhood outcomes. We did not find associations with any of the other outcomes. This study supports early and possibly transient effects of prenatal n-3 LCPUFA status on anthropometric measures and adipokine levels. It also raises the possibility that offspring of women with isolated hyperglycemia derive the most benefits from higher n-3 LCPUFA status. PMID- 29795534 TI - Oxygen and Pt(II) self-generating conjugate for synergistic photo-chemo therapy of hypoxic tumor. AB - Cancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy. Here, we hypothesize that an oxygen and Pt(II) self-generating multifunctional nanocomposite could reverse the hypoxia-triggered PDT resistance. The nanocomposite contains Pt(IV) and chlorin e6, in which upconversion nanoparticles are loaded to convert 980 nm near-infrared light into 365 nm and 660 nm emissions. Upon accumulation at the tumor site, a 980 nm laser is used to trigger the nanocomposite to generate O2 for consumption in the PDT process and to produce cytotoxic reactive oxygen species. The composite also releases active Pt(II) for synergistic photo-chemo therapy to enhance antitumor efficiency. The oxygen and Pt(II) self-generating prodrug is shown to have high potential to inhibit tumors out of the range of UV light, to overcome the hypoxia-triggered PDT resistance and significantly improve anticancer efficacy by the synergistic PDT-chemotherapy. PMID- 29795536 TI - Evolution of human malaria. PMID- 29795537 TI - CRISPR still needs microbiologists. PMID- 29795535 TI - Evolutionary adaptation of an RNA bacteriophage to the simultaneous increase in the within-host and extracellular temperatures. AB - Bacteriophages are the most numerous biological entities on Earth. They are on the basis of most ecosystems, regulating the diversity and abundance of bacterial populations and contributing to the nutrient and energy cycles. Bacteriophages have two well differentiated phases in their life cycle, one extracellular, in which they behave as inert particles, and other one inside their hosts, where they replicate to give rise to a progeny. In both phases they are exposed to environmental conditions that often act as selective pressures that limit both their survival in the environment and their ability to replicate, two fitness traits that frequently cannot be optimised simultaneously. In this study we have analysed the evolutionary ability of an RNA bacteriophage, the bacteriophage Qbeta, when it is confronted with a temperature increase that affects both the extracellular and the intracellular media. Our results show that Qbeta can optimise its survivability when exposed to short-term high temperature extracellular heat shocks, as well as its replicative ability at higher-than optimal temperature. Mutations responsible for simultaneous adaptation were the same as those selected when adaptation to each condition proceeded separately, showing the absence of important trade-offs between survival and reproduction in this virus. PMID- 29795538 TI - A common approach to toxin specificity. PMID- 29795539 TI - Aerobic Archaea in iron-rich springs. PMID- 29795540 TI - Methods for phylogenetic analysis of microbiome data. AB - How does knowing the evolutionary history of microorganisms affect our analysis of microbiological datasets? Depending on the research question, the common ancestry of microorganisms can be a source of confounding variation, or a scaffolding used for inference. For example, when performing regression on traits, common ancestry is a source of dependence among observations, whereas when searching for clades with correlated abundances, common ancestry is the scaffolding for inference. The common ancestry of microorganisms and their genes are organized in trees-phylogenies-which can and should be incorporated into analyses of microbial datasets. While there has been a recent expansion of phylogenetically informed analytical tools, little guidance exists for which method best answers which biological questions. Here, we review methods for phylogeny-aware analyses of microbiome datasets, considerations for choosing the appropriate method and challenges inherent in these methods. We introduce a conceptual organization of these tools, breaking them down into phylogenetic comparative methods, ancestral state reconstruction and analysis of phylogenetic variables and distances, and provide examples in Supplementary Online Tutorials. Careful consideration of the research question and ecological and evolutionary assumptions will help researchers choose a phylogeny and appropriate methods to produce accurate, biologically informative and previously unreported insights. PMID- 29795542 TI - Epidemiology of healthcare-associated infections in Polish intensive care. A multicenter study based on active surveillance. AB - AIM: The aim of this study was to evaluate the incidence of health care associated infections (HAIs) in patients treated in Polish intensive care units (ICUs). METHODS: This retrospective analysis was based on the results of active targeted surveillance, according to the recommendation of the ECDC (European Centre of Disease Control and Prevention, HAI-Net light protocol), conducted in 2013-2015 in seven ICUs for adults located in southern Poland (observational study). RESULTS: The incidence of HAI was 22.6% and 28.7/1000 person-days (pds). The incidence of pneumonia (PN) was 8.0%, bloodstream infections (BSIs) 7.2% and urinary tract infections (UTIs) 3.7%. The incidence per 1000 pds was as follows: PN 10.2, BSIs 9.2 and UTIs 4.7. PN was the most common source of secondary bloodstream infection (45%); the second was UTIs (22%). Mortality (directly and indirectly) associated with HAI was 10.8% and was related to the presence of PN or primary BSIs. HAIs were usually (69.2%) caused by Gram-negative bacteria; Klebsiella spp. and nonfermenting Gram-negative rods demonstrated very high antibiotic resistance. CONCLUSION: Despite the lack of widely implemented active targeted surveillance programmes and top-down incentives, it is possible to carry out effective surveillance of HAIs in ICUs in Poland. The results of this study are comparable with the ECDC data, but the results are alarmingly high in two fields: epidemiology of PN and BSIs and very high antibiotic resistance in Gram negative rods, which indicate the need for intense control in this area and for further studies to clarify the source of the observed discrepancy. PMID- 29795541 TI - Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. AB - Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic resistant infections. PMID- 29795543 TI - Extraction of a dislocated leadless pacemaker in a patient with infective endocarditis and repeated endocardial and epicardial pacing system infections. AB - BACKGROUND: Leadless pacemakers (PMs) were recently introduced to address the complication rate of standard PMs with transvenous leads. METHODS AND RESULTS: A 34-year old male with a history of intravenous substance abuse and a chronic type C hepatitis developed a complete atrioventricular block after cardiac surgery for infective endocarditis. Repeatedly, endo- and epi-cardially implanted PMs had to be explanted due to infection. A leadless MICRA pacemaker was successfully implanted with a dislocation into pulmonary artery several days after implantation. The PM was successfully retrieved using a single-loop retrieval snare guided by a steerable sheath. Subsequently, another Micra PM was successfully implanted with no further issues. CONCLUSION: In the case of a Micra leadless pacemaker dislocation, a conventional gooseneck snare in combination with a steerable sheath can be used to retrieve the device, improving the overall safety of leadless pacemakers. PMID- 29795544 TI - The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability. AB - BACKGROUND: The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation. METHODS: A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20 minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention. RESULTS: The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity. CONCLUSION: The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two. PMID- 29795545 TI - Early manifestation of spasticity after first stroke in the territory of the internal carotid artery: A prospective multicenter study. AB - AIMS: The main aim of this study was to provide an estimate of the incidence and prevalence of spasticity following stroke in the internal carotid artery territory for Regional Stroke Centers in the Czech Republic. A secondary goal was to identify predictors for the development of spasticity. METHODS: In a prospective cohort study, 256 consecutive patients with clinical signs of central paresis due to a first-ever stroke were examined in the acute stage. All patients had primary stroke of carotid origin and paresis of the upper and/or lower limb for longer than 7 days after stroke onset. All were examined between 7-10 days after the stroke. We evaluated the degree and pattern of paresis, spasticity using the Modified Ashworth scale and the Barthel Index, baseline characteristics and demographic data. RESULTS: Of 256 patients (157 males; mean age 69.9+/-12.4 years), 115 (44.9%) patients developed spasticity during the first 10 days after stroke onset. Eighty-three (32.5%) patients presented with mild neurological deficit (modified Rankin Scale 0 - 2) and 69 (27.0%) patients were bedridden. CONCLUSION: Spasticity was noted in 44.9% patients with neurological deficit due to first-ever stroke in the carotid territory in the first 10 days after stroke onset. Severe spasticity was rare. PMID- 29795546 TI - Unsolved mysteries: How does lipid peroxidation cause ferroptosis? AB - Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases. PMID- 29795548 TI - Design of optimal nonlinear network controllers for Alzheimer's disease. AB - Brain stimulation can modulate the activity of neural circuits impaired by Alzheimer's disease (AD), having promising clinical benefit. However, all individuals with the same condition currently receive identical brain stimulation, with limited theoretical basis for this generic approach. In this study, we introduce a control theory framework for obtaining exogenous signals that revert pathological electroencephalographic activity in AD at a minimal energetic cost, while reflecting patients' biological variability. We used anatomical networks obtained from diffusion magnetic resonance images acquired by the Alzheimer's Disease Neuroimaging Initiative (ADNI) as mediators for the interaction between Duffing oscillators. The nonlinear nature of the brain dynamics is preserved, given that we extend the so-called state-dependent Riccati equation control to reflect the stimulation objective in the high-dimensional neural system. By considering nonlinearities in our model, we identified regions for which control inputs fail to correct abnormal activity. There are changes to the way stimulated regions are ranked in terms of the energetic cost of controlling the entire network, from a linear to a nonlinear approach. We also found that limbic system and basal ganglia structures constitute the top target locations for stimulation in AD. Patients with highly integrated anatomical networks-namely, networks having low average shortest path length, high global efficiency-are the most suitable candidates for the propagation of stimuli and consequent success on the control task. Other diseases associated with alterations in brain dynamics and the self-control mechanisms of the brain can be addressed through our framework. PMID- 29795547 TI - Yeast heterochromatin regulators Sir2 and Sir3 act directly at euchromatic DNA replication origins. AB - Most active DNA replication origins are found within euchromatin, while origins within heterochromatin are often inactive or inhibited. In yeast, origin activity within heterochromatin is negatively controlled by the histone H4K16 deacetylase, Sir2, and at some heterochromatic loci also by the nucleosome binding protein, Sir3. The prevailing view has been that direct functions of Sir2 and Sir3 are confined to heterochromatin. However, growth defects in yeast mutants compromised for loading the MCM helicase, such as cdc6-4, are suppressed by deletion of either SIR2 or SIR3. While these and other observations indicate that SIR2,3 can have a negative impact on at least some euchromatic origins, the genomic scale of this effect was unknown. It was also unknown whether this suppression resulted from direct functions of Sir2,3 within euchromatin, or was an indirect effect of their previously established roles within heterochromatin. Using MCM ChIP-Seq, we show that a SIR2 deletion rescued MCM complex loading at ~80% of euchromatic origins in cdc6-4 cells. Therefore, Sir2 exhibited a pervasive effect at the majority of euchromatic origins. Using MNase-H4K16ac ChIP-Seq, we show that origin-adjacent nucleosomes were depleted for H4K16 acetylation in a SIR2 dependent manner in wild type (i.e. CDC6) cells. In addition, we present evidence that both Sir2 and Sir3 bound to nucleosomes adjacent to euchromatic origins. The relative levels of each of these molecular hallmarks of yeast heterochromatin SIR2-dependent H4K16 hypoacetylation, Sir2, and Sir3 -correlated with how strongly a SIR2 deletion suppressed the MCM loading defect in cdc6-4 cells. Finally, a screen for histone H3 and H4 mutants that could suppress the cdc6-4 growth defect identified amino acids that map to a surface of the nucleosome important for Sir3 binding. We conclude that heterochromatin proteins directly modify the local chromatin environment of euchromatic DNA replication origins. PMID- 29795549 TI - Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics. AB - Success rates for catheter ablation of persistent atrial fibrillation patients are currently low; however, there is a subset of patients for whom electrical isolation of the pulmonary veins alone is a successful treatment strategy. It is difficult to identify these patients because there are a multitude of factors affecting arrhythmia susceptibility and maintenance, and the individual contributions of these factors are difficult to determine clinically. We hypothesised that the combination of pulmonary vein (PV) electrophysiology and atrial body fibrosis determine driver location and effectiveness of pulmonary vein isolation (PVI). We used bilayer biatrial computer models based on patient geometries to investigate the effects of PV properties and atrial fibrosis on arrhythmia inducibility, maintenance mechanisms, and the outcome of PVI. Short PV action potential duration (APD) increased arrhythmia susceptibility, while longer PV APD was found to be protective. Arrhythmia inducibility increased with slower conduction velocity (CV) at the LA/PV junction, but not for cases with homogeneous CV changes or slower CV at the distal PV. Phase singularity (PS) density in the PV region for cases with PV fibrosis was increased. Arrhythmia dynamics depend on both PV properties and fibrosis distribution, varying from meandering rotors to PV reentry (in cases with baseline or long APD), to stable rotors at regions of high fibrosis density. Measurement of fibrosis and PV properties may indicate patient specific susceptibility to AF initiation and maintenance. PV PS density before PVI was higher for cases in which AF terminated or converted to a macroreentry; thus, high PV PS density may indicate likelihood of PVI success. PMID- 29795550 TI - Metabolomics analysis of Lactobacillus plantarum ATCC 14917 adhesion activity under initial acid and alkali stress. AB - The adhesion ability of Lactobacillus plantarum affects retention time in the human gastro-intestinal tract, as well as influencing the interaction with their host. In this study, the relationship between the adhesion activity of, and metabolic changes in, L. plantarum ATCC 14917 under initial acid and alkali stress was evaluated by analyzing auto-aggregation, protein adhesion and cell adhesion in vitro. Based on scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis, the morphology of the bacteria became thickset and the thickness of their cell walls decreased under initial alkali stress. The fold changes of auto-aggregation, adhere to mucin and HT-29 cell lines of L. plantarum ATCC 14917 in the acid group were increased by 1.141, 1.125 and 1.156, respectively. But decreased significantly in the alkali group (fold changes with 0.842, 0.728 and 0.667). Adhesion-related protein increased in the acid group but declined in the alkali group at the mRNA expression level according to real time polymerase chain reaction (RT-PCR) analysis. The changes in the metabolite profiles of L. plantarum ATCC 14917 were characterized using Ultra-Performance Liquid Chromatography-Electrospray ionization-Quadrupole-Time of Flight-mass spectrometry (UPLS-ESI-Q-TOF-MS). In the alkali group, the content of a lot of substances involved in the energy and amino acid metabolism decreased, but the content of some substances involved in the energy metabolism was slightly increased in the acid group. These findings demonstrate that energy metabolism is positively correlated with the adhesion ability of L. plantarum ATCC 14917. The amino-acids metabolism, especially the amino acids related to pH homeostasis mechanisms (lysine, aspartic acid, arginine, proline and glutamic acid), showed an obvious effect on the adhesion ability of L. plantarum ATCC 14917. This investigation provides a better understanding of L. plantarum's adhesion mechanisms under initial pH stress. PMID- 29795551 TI - "Rapid impact" 10 years after: The first "decade" (2006-2016) of integrated neglected tropical disease control. PMID- 29795552 TI - Coordinated regulation of core and accessory genes in the multipartite genome of Sinorhizobium fredii. AB - Prokaryotes benefit from having accessory genes, but it is unclear how accessory genes can be linked with the core regulatory network when developing adaptations to new niches. Here we determined hierarchical core/accessory subsets in the multipartite pangenome (composed of genes from the chromosome, chromid and plasmids) of the soybean microsymbiont Sinorhizobium fredii by comparing twelve Sinorhizobium genomes. Transcriptomes of two S. fredii strains at mid-log and stationary growth phases and in symbiotic conditions were obtained. The average level of gene expression, variation of expression between different conditions, and gene connectivity within the co-expression network were positively correlated with the gene conservation level from strain-specific accessory genes to genus core. Condition-dependent transcriptomes exhibited adaptive transcriptional changes in pangenome subsets shared by the two strains, while strain-dependent transcriptomes were enriched with accessory genes on the chromid. Proportionally more chromid genes than plasmid genes were co-expressed with chromosomal genes, while plasmid genes had a higher within-replicon connectivity in expression than chromid ones. However, key nitrogen fixation genes on the symbiosis plasmid were characterized by high connectivity in both within- and between-replicon analyses. Among those genes with host-specific upregulation patterns, chromosomal znu and mdt operons, encoding a conserved high-affinity zinc transporter and an accessory multi-drug efflux system, respectively, were experimentally demonstrated to be involved in host-specific symbiotic adaptation. These findings highlight the importance of integrative regulation of hierarchical core/accessory components in the multipartite genome of bacteria during niche adaptation and in shaping the prokaryotic pangenome in the long run. PMID- 29795553 TI - Chromosome 1 licenses chromosome 2 replication in Vibrio cholerae by doubling the crtS gene dosage. AB - Initiation of chromosome replication in bacteria is precisely timed in the cell cycle. Bacteria that harbor multiple chromosomes face the additional challenge of orchestrating replication initiation of different chromosomes. In Vibrio cholerae, the smaller of its two chromosomes, Chr2, initiates replication after Chr1 such that both chromosomes terminate replication synchronously. The delay is due to the dependence of Chr2 initiation on the replication of a site, crtS, on Chr1. The mechanism by which replication of crtS allows Chr2 replication remains unclear. Here, we show that blocking Chr1 replication indeed blocks Chr2 replication, but providing an extra crtS copy in replication-blocked Chr1 permitted Chr2 replication. This demonstrates that unreplicated crtS copies have significant activity, and suggests that a role of replication is to double the copy number of the site that sufficiently increases its activity for licensing Chr2 replication. We further show that crtS activity promotes the Chr2-specific initiator function and that this activity is required in every cell cycle, as would be expected of a cell-cycle regulator. This study reveals how increase of gene dosage through replication can be utilized in a critical regulatory switch. PMID- 29795554 TI - Who is research serving? A systematic realist review of circumpolar environment related Indigenous health literature. AB - BACKGROUND: Addressing factors leading to health disparities in the Circumpolar North require approaches that consider and address the social determinants of health including on-going colonization. Today, colonization and related policies and processes, continue to manifest in the marginalization of Indigenous knowledge, particularly its use in research; however, Indigenous populations have moved from being research subjects to leaders and consumers of environmental health research. Given the tensions that exist between how health research is conducted, how the results are mobilized, and who has control and access to the results, we examine how peer-reviewed environment-related Indigenous health research in the Circumpolar North is serving the needs of Indigenous communities, governments, and organizations. METHODS: A modified systematic-realist literature review was conducted. Three databases were searched for peer-reviewed literature published from 2000 to 2015. Articles were included if the research focused on the intersection of the environment and health in Northern Canada and/or Alaska. A total of 960 unique records were screened for relevance, and 210 articles were analysed. RESULTS: Of these relevant articles, 19% discussed how Indigenous peoples were engaged in the research. There was a significant increase in reporting participatory, community-based methods over time; the proportion of articles reporting community-engagement varied by research topic; quantitative research articles were significantly less likely to report community-engaged methods; and most articles did not clearly report how the results were shared with the community. CONCLUSION: The results raise a number of questions for the field of Circumpolar environment-related Indigenous health research, including whether or how authors of peer-reviewed literature should (or should not) be obliged to describe how research is serving Northern Indigenous communities. The results are intended to stimulate further conversations and bridge perceived dichotomies of quantitative/qualitative, Western/Indigenous, and empirical/community driven research approaches, as well as underlying assumptions that frame health research. PMID- 29795555 TI - MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. AB - Three waves of H2AX phosphorylation (gammaH2AX) have been observed in male meiotic prophase I: the first is ATM-dependent and occurs at leptonema, while the second and third are ATR-dependent, occuring at zygonema and pachynema, respectively. The third wave of H2AX phosphorylation marks and silences unsynapsed chromosomes. Little is known about H2AX phosphorylation expands to chromatin-wide regions in spermatocytes. Here, we report that histone acetyltransferase (HAT) MOF is involved in all three waves of H2AX phosphorylation expansion. Germ cell-specific deletion of Mof in spermatocytes by Stra8-Cre (Mof cKO) caused global loss of H4K16ac. In leptotene and zygotene spermatocytes of cKO mice, the gammaH2AX signals were observed only along the chromosomal axes, and chromatin-wide H2AX phosphorylation was lost. In almost 40% of early-mid pachytene spermatocytes from Mof cKO mice, gammaH2AX and MDC1 were detected along the unsynapsed axes of the sex chromosomes, but failed to expand, which consequently caused meiotic sex chromosome inactivation (MSCI) failure. Furthermore, though RAD51 was proficiently recruited to double-strand break (DSB) sites, defects in DSB repair and crossover formation were observed in Mof cKO spermatocytes, indicating that MOF facilitates meiotic DSB repair after RAD51 recruitment. We propose that MOF regulates male meiosis and is involved in the expansion of all three waves of H2AX phosphorylation from the leptotene to pachytene stages, initiated by ATM and ATR, respectively. PMID- 29795556 TI - Ancestry-specific recent effective population size in the Americas. AB - Populations change in size over time due to factors such as population growth, migration, bottleneck events, natural disasters, and disease. The historical effective size of a population affects the power and resolution of genetic association studies. For admixed populations, it is not only the overall effective population size that is of interest, but also the effective sizes of the component ancestral populations. We use identity by descent and local ancestry inferred from genome-wide genetic data to estimate overall and ancestry specific effective population size during the past hundred generations for nine admixed American populations from the Hispanic Community Health Study/Study of Latinos, and for African-American and European-American populations from two US cities. In these populations, the estimated pre-admixture effective sizes of the ancestral populations vary by sampled population, suggesting that the ancestors of different sampled populations were drawn from different sub-populations. In addition, we estimate that overall effective population sizes dropped substantially in the generations immediately after the commencement of European and African immigration, reaching a minimum around 12 generations ago, but rebounded within a small number of generations afterwards. Of the populations that we considered, the population of individuals originating from Puerto Rico has the smallest bottleneck size of one thousand, while the Pittsburgh African American population has the largest bottleneck size of two hundred thousand. PMID- 29795557 TI - Patterns of livestock depredation by tiger (Panthera tigris) and leopard (Panthera pardus) in and around Corbett Tiger Reserve, Uttarakhand, India. AB - India with estimated more than 2000 tigers (across 18 states) accounts for more than half of the remaining tigers across its range countries. Long-term conservation requires measures to protect the large carnivores and its prey base beyond the Protect Areas. The Corbett Tiger Reserve (CTR) and adjoining forest divisions with high density of tigers play a crucial role in conservation of tiger in Uttarakhand state as well as the Terai-Arc Landscape. However, CTR is surrounded with multiple-use forest (forest divisions), agriculture land, human habitation, townships and developmental projects. The movement of large carnivores and other wildlife through such habitats adds to the chances of human wildlife conflict. The aim of the current study was to understand the patterns of livestock depredation by tigers and leopards in and around CTR. We examined a total of 8365 incidents of livestock depredation between 2006 and 2015 with tigers killing more livestock in a year (573.3+/-41.2) than leopards (263.2+/ 9.9). Geographically, in north zone of CTR leopards were the major livestock predator (166.6+/-11), whereas tigers (547.7+/-40.1) in south zone. Examination of livestock kills indicated cows (75%) as the main victim, followed by buffaloes and other species. Analysis revealed that the livestock depredation by tigers varied significantly among seasons in south zone but not in north zone. However, such an explicit seasonal variation was not observed for leopards in north and south zone of CTR. Hotspots of livestock predation were identified around CTR. Addressing a conflict situation in a time-bound manner, timely disbursement of ex gratia payment, involving locals at various tourism related activities and consistent rapport building initiatives are required to mitigate the human wildlife conflict. PMID- 29795558 TI - Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients. AB - Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naive HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naive to ART (298 +/- 243 cells/mm3) was significantly lower than that of patients on ART (604 +/- 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 +/- 15073 copies/mm3) compared to the ART naive group (209882 +/- 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81-51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients. PMID- 29795559 TI - Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent. AB - Serum albumin is the major intravascular antioxidant. Though oxidative stress plays an important role in the pathophysiology of Immunoglobulin A nephropathy (IgAN), the association between serum albumin and the progression of IgAN is not entirely understood. This retrospective cohort study of 1,352 participants with biopsy-proven IgAN determined the associations between serum albumin level and the incidence of end-stage renal disease (ESRD) using a Cox proportional hazards model. Patients were divided into three groups by tertiles of serum albumin level: Low, Middle, and High group (<=3.9 g/dL, 4.0-4.3 g/dL, >=4.4 g/dL, respectively). During the median 5.1-year follow-up period, 152 patients (11.2%) developed ESRD. Participants in the Low group had a 1.88-fold increased risk for ESRD compared with those in the High group after adjustment for clinical parameters, including urinary protein excretion, and pathological parameters (Oxford classification). We also experimentally proved the antioxidant capacity of albumin on mesangial cells. The intracellular reactive oxygen species and mitochondrial injury, induced by hydrogen peroxide were significantly attenuated in albumin-pretreated mouse mesangial cells and human kidney cells compared with gamma-globulin-pretreated cells. Low serum albumin level is an independent risk factor for ESRD in patients with IgAN. The mechanism could be explained by the antioxidant capacity of serum albumin. PMID- 29795560 TI - Zika virus infection in the Veterans Health Administration (VHA), 2015-2016. AB - BACKGROUND: Zika virus (ZIKV) is an important flavivirus infection. Although ZIKV infection is rarely fatal, risk for severe disease in adults is not well described. Our objective was to describe the spectrum of illness in U.S. Veterans with ZIKV infection. METHODOLOGY: Case series study including patients with laboratory-confirmed or presumed positive ZIKV infection in all Veterans Health Administration (VHA) medical centers. Adjusted odds ratios of clinical variables associated with hospitalization and neurologic complications was performed. PRINCIPAL FINDINGS: Of 1,538 patients tested between 12/2015-10/2016 and observed through 3/2017, 736 (48%) were RT-PCR or confirmed IgM positive; 655 (89%) were male, and 683 (93%) from VA Caribbean Healthcare System (VACHCS). Ninety-four (13%) were hospitalized, 91 (12%) in the VACHCS. Nineteen (3%) died after ZIKV infection. Hospitalization was associated with increased Charlson co-morbidity index (adjusted odds ratio [OR] 1.2; 95% confidence interval [CI], 1.1-1.3), underlying connective tissue disease (OR, 29.5; CI, 3.6-244.7), congestive heart failure (OR, 6; CI, 2-18.5), dementia (OR, 3.6; CI, 1.1-11.2), neurologic symptom presentation (OR, 3.9; CI, 1.7-9.2), leukocytosis (OR, 11.8; CI, 4.5-31), thrombocytopenia (OR, 7.8; CI, 3.3-18.6), acute kidney injury (OR, 28.9; CI, 5.8 145.1), or using glucocorticoids within 30 days of testing (OR, 13.3; CI 1.3 133). Patients presenting with rash were less likely to be hospitalized (OR, 0.29; CI, 0.13-0.66). Risk for neurologic complications increased with hospitalization (OR, 5.9; CI 2.9-12.2), cerebrovascular disease (OR 4.9; CI 1.7 14.4), and dementia (OR 2.8; CI 1.2-6.6). CONCLUSION: Older Veterans with multiple comorbidities or presenting with neurologic symptoms were at increased risk for hospitalization and neurological complications after ZIKV infection. PMID- 29795561 TI - Association of serum high-mobility group box protein 1 level with outcomes of acute exacerbation of idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia. AB - BACKGROUND AND OBJECTIVE: High-mobility group box 1 (HMGB1) protein is important in acute lung injury. However, the role of HMGB-1 in acute exacerbation of fibrosing interstitial pneumonia (AE-FIP) has not been adequately studied. METHODS: We prospectively measured serum HMGB1 level from disease onset to day 7 in 36 patients with AE-FIP6 patients had missing data because of early death (within 7 days). We then examined the association of HMGB1 level and outcome, and the associations of rhTM with HMGB1 level and outcome in 19 patients who were treated with rhTM (rhTM group) and 11 patients who were not (control group). RESULTS: Data from 36 AE-FIP patients (mean age, 73.5+/-6.7years) were analyzed. Serum HMGB1 level was significantly higher in patients with AE-FIP than in those with stable idiopathic pulmonary fibrosis (16.4+/-13.5 vs 5.7+/-2.6 ng/ml, respectively; p = 0.003). HMGB1 was significantly lower on day 7 than at AE-FIP onset in survivors (6.5+/-4.8 vs 14.7+/-12.9 ng/ml, respectively; p = 0.02) but not in nonsurvivors (14.6+/-10.5 vs 9.2+/-4.8 ng/ml, respectively; p = 0.08). Although HMGB1 level at day 7 was significantly lower after rhTM treatment than at AE-FIP onset (8.4+/-6.1 vs 15.2+/-12.5 ng/ml, respectively; p = 0.02), it did not significantly decrease in patients receiving treatments other than rhTM (11.3+/-11.3 vs 8.3+/-5.3 ng/ml, respectively; p = 0.37). Three-month survival was 60.0% in the rhTM group and 36.4% in the control group (p = 0.449). In multivariate analysis, a decrease in HMGB1 was a significant independent predictor of 3-month survival (Odds ratio, 12.4; p = 0.007). CONCLUSION: rhTM lowers serum HMGB1 level and may improve survival after AE-FIP. HMGB1 may be a promising therapeutic target for AE-FIP. PMID- 29795562 TI - Dynamics of soil nitrogen fractions and their relationship with soil microbial communities in two forest species of northern China. AB - Microbially-mediated soil N mineralization and transformation are crucial to plant growth. However, changes in soil microbial groups and various N components are not clearly understood. To explore the relationship between soil N components and microbial communities, we conducted an in-situ experiment on two typically planted forest species, namely, Sibirica Apricot (SA) and Prunus davidiana Franch (PdF) by using closed-top polyvinyl chloride tubes. Changes in soil inorganic N, organic N (ON) fractions, and levels of microbial phospholipid fatty acids (PLFAs) were measured bimonthly from April 2012 to April 2013. Microbial PLFAs and the concentrations of easily-available microbial biomass N (MBN; ~60 mg kg 1), soluble ON (SON; ~20 mg kg-1), and inorganic N were similar between the two soils whereas the ON (~900 mg kg-1) and its major part total acid-hydrolyzable N (HTN; ~500 mg kg-1), were significantly different (p < 0.05) in most months (5/6 and 4/6; respectively). The canonical correlation analysis of soil N fractions and microbial parameters indicated that the relationship between total PLFAs (total biomass of living cells) and NH4+-N was the most representative. The relative contributions (indicated by the absolute value of canonical coefficient) of NH4+-N were the largest, followed by NO3--N and MBN. For the HTN component, the relative percentage of hydrolyzable amino acid N and ammonium N decreased markedly in the first half of the year. Canonical variation mainly reflected the relationship between ammonium N and bacterial PLFAs, which were the most sensitive indicators related to soil N changes. The relative contributions of HTN components to the link between soil microbial groups and HTN components were ammonium N > amino acid N > amino sugar N. Observations from our study indicate the sensitivity of soil N mineralization indicators in relation to the temporal variation of soil microbial groups and N fractions. PMID- 29795563 TI - Psychometric evaluation of the Chinese version of the fear of intimacy with helping professionals scale. AB - OBJECTIVES: This study aimed to evaluate the internal consistency, reliability, convergent validity, known-group comparisons, and structural validity of the Chinese version of Fear of Intimacy with Helping Professionals (C-FIS-HP) scale in Macau. METHODS: A cross-sectional design was used on a sample of 593 older people in 6 health centers. We used Chinese version of Exercise of Self-Care Agency Scale (C-ESCAS) and Morisky 4-item medication adherence scale to evaluate self-care actions and medication adherence. The internal consistency and reliability of C-FIS-HP were analyzed using the Spearman-Brown split-half reliability, Cronbach's alpha, and test-retest reliability. Convergent validity was tested the construct of C-FIS-HP and self-care actions. Known-group comparisons differentiated predefined groups in an expected direction. Two separated samples were used to test the structural validity. An exploratory factor analysis (EFA) tested the factor structure of C-FISHP using the principal axis factoring. A confirmatory factor analysis (CFA) was further conducted to confirm the factor structure constructed in the prior EFA. RESULTS: The C-FIS-HP had a Spearman-Brown split-half coefficient, Cronbach's alpha, and intraclass correlation coefficient of 0.96, 0.93, and 0.96, respectively. Convergent validity was satisfactory with significantly correlations between the C-FIS-HP and C-ESCAS. C-FIS-HP to differentiate the differences between high-, moderate-, and low- medication adherence groups. EFA demonstrated a two-factor structure among 297 older people. A first-order CFA was performed to confirm the construct dimensionality of C-FIS-HP with satisfactory fit indices (NFI = 0.92; IFI = 0.95; TLI = 0.94; CFI = 0.95 and RMSEA = 0.07) among 296 older people. CONCLUSIONS: C FIS-HP is a reliable and valid test for assessing helping relationships in older Chinese people. Health professionals can use C-FIS-HP as a clinical tool to assess the comfort level of patients in a helping relationship, and use this information to develop culturally sensitive therapeutic interventions and treatment plans. Further studies need to be conducted concerning the different psychometric properties, as well as the application of C-FIS-HP in various regions. PMID- 29795564 TI - Expression and clinical significance of survivin in ovarian cancer: A meta analysis. AB - To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle-Ottawa Scale (NOS) for quality assessment of case-control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma. PMID- 29795566 TI - Consensus criteria for the diagnosis of scabies: A Delphi study of international experts. AB - BACKGROUND: Scabies was added to the WHO Neglected Tropical Diseases portfolio in 2017, and further understanding of the disease burden is now required. There are no uniformly accepted test methods or examination procedures for diagnosis, which limits the interpretation of research and epidemiological findings. The International Alliance for the Control of Scabies (IACS) designated harmonization of diagnostic procedures as a priority for the development of a global control strategy. Therefore, we aimed to develop consensus criteria for the diagnosis of scabies. METHODOLOGY / PRINCIPAL FINDINGS: We conducted an iterative, consensus (Delphi) study involving international experts in the diagnosis of scabies. Panel members were recruited through expression of interest and targeted invitation of experts. The Delphi study consisted of four rounds of anonymous surveys. Rounds 1 and 2 involved generation and ranking an extensive list of possible features. In Rounds 3 and 4, participants were presented results from previous rounds and indicated agreement with a series of draft criteria. Panel participants (n = 34, range per Round 28-30) were predominantly highly experienced clinicians, representing a range of clinical expertise and all inhabited continents. Based on initial rounds, a draft set of criteria were developed, incorporating three levels of diagnostic certainty-Confirmed Scabies, Clinical Scabies and Suspected Scabies. Consensus was reached in Round 4, with a very high level of agreement (> 89%) for all levels of criteria and subcategories. Adoption of the criteria was supported by 96% of panel members. CONCLUSIONS / SIGNIFICANCE: Consensus criteria for scabies diagnosis were established with very high agreement. The 2018 IACS Criteria for the Diagnosis of Scabies can be implemented for scabies research and mapping projects, and for surveillance after control interventions. Validation of the criteria is required. PMID- 29795565 TI - Identification of alterations associated with age in the clustering structure of functional brain networks. AB - Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems. PMID- 29795568 TI - Land-based crop phenotyping by image analysis: Accurate estimation of canopy height distributions using stereo images. AB - In this paper we report on an automated procedure to capture and characterize the detailed structure of a crop canopy by means of stereo imaging. We focus attention specifically on the detailed characteristic of canopy height distribution-canopy shoot area as a function of height-which can provide an elaborate picture of canopy growth and health under a given set of conditions. We apply the method to a wheat field trial involving ten Australian wheat varieties that were subjected to two different fertilizer treatments. A novel camera self calibration approach is proposed which allows the determination of quantitative plant canopy height data (as well as other valuable phenotypic information) by stereo matching. Utilizing the canopy height distribution to provide a measure of canopy height, the results compare favourably with manual measurements of canopy height (resulting in an R2 value of 0.92), and are indeed shown to be more consistent. By comparing canopy height distributions of different varieties and different treatments, the methodology shows that different varieties subjected to the same treatment, and the same variety subjected to different treatments can respond in much more distinctive and quantifiable ways within their respective canopies than can be captured by a simple trait measure such as overall canopy height. PMID- 29795567 TI - Neonatal and maternal serum creatinine levels during the early postnatal period in preterm and term infants. AB - We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman's test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born <29 weeks, pregnancy-induced hypertension (PIH) (p = 0.000, beta = 0.20) and mSCr (p = 0.000, beta = 0.73) were significantly associated with nSCr. In term infants, maternal magnesium administration (p = 0.000, beta = 0.25), respiratory distress syndrome (p = 0.013, beta = 0.16), PIH (p = 0.005, beta = 0.19), and mSCr (p = 0.000, beta = 0.33) were significantly associated with nSCr. nSCr reflected mSCr at all gestational ages. The correlation between nSCr and mSCr in preterm infants (p = 0.000, beta = 0.74) was stronger than in term infants (p = 0.000, beta = 0.34). PMID- 29795569 TI - Associations between sleep duration, sleep quality and diabetic retinopathy. AB - BACKGROUND: Abnormal durations of sleep have been associated with risk of diabetes. However, it is not clear if sleep duration is associated with diabetic retinopathy (DR). METHODS: In a cross-sectional study, we included 1,231 (Malay, n = 395; Indian, n = 836) adults (mean age 64.4 +/- 9.0 years, 50.4% female) with diabetes from the second visit of two independent population-based cohort studies (2011-15) in Singapore. Self-reported habitual sleep duration was categorized as short (<6 h), normal (6<= h <8), and long (>=8 h). Questionnaires were administered to detect risk of obstructive sleep apnea (OSA), excessive daytime sleepiness, and insomnia, all of which may indicate poor quality of sleep. The associations between sleep-related characteristics with moderate DR and vision threatening DR (VTDR) were analysed using logistic regression models adjusted for potential confounders. RESULTS: Prevalence of moderate DR and VTDR in the study population were 10.5% and 6.3% respectively. The mean duration of sleep was 6.4 +/- 1.5 h. Compared to normal sleep duration, both short and long sleep durations were associated with moderate DR with multivariable odds ratio (95% confidence interval) of 1.73 (1.03-2.89) and 2.17 (1.28-3.66) respectively. Long sleep duration (2.37 [1.16-4.89]), high risk of OSA (2.24 [1.09-4.75]), and excessive daytime sleepiness (3.27 [1.02-10.30]) were separately associated with VTDR. CONCLUSION: Sleep duration had a U-shaped association with moderate DR; long sleep duration, excessive daytime sleepiness and high risk of OSA were positively associated with VTDR. PMID- 29795571 TI - The complex ecosystem in non small cell lung cancer invasion. AB - Many tumors are characterized by genetic instability, producing an assortment of genetic variants of tumor cells called subclones. These tumors and their surrounding environments form complex multi-cellular ecosystems, where subclones compete for resources and cooperate to perform multiple tasks, including cancer invasion. Our recent empirical studies revealed existence of such distinct phenotypes of cancer cells, leaders and followers, in lung cancer. These two cellular subclones exchange a complex array of extracellular signals demonstrating a symbiotic relationship at the cellular level. Here, we develop a computational model of the microenvironment of the lung cancer ecosystem to explore how the interactions between subclones can advance or inhibit invasion. We found that, due to the complexity of the ecosystem, invasion may have very different dynamics characterized by the different levels of aggressiveness. By altering the signaling environment, we could alter the ecological relationship between the cell types and the overall ecosystem development. Competition between leader and follower cell populations (defined by the limited amount of resources), positive feedback within the leader cell population (controlled by the focal adhesion kinase and fibronectin signaling), and impact of the follower cells to the leaders (represented by yet undetermined proliferation signal) all had major effects on the outcome of the collective dynamics. Specifically, our analysis revealed a class of tumors (defined by the strengths of fibronectin signaling and competition) that are particularly sensitive to manipulations of the signaling environment. These tumors can undergo irreversible changes to the tumor ecosystem that outlast the manipulations of feedbacks and have a profound impact on invasive potential. Our study predicts a complex division of labor between cancer cell subclones and suggests new treatment strategies targeting signaling within the tumor ecosystem. PMID- 29795572 TI - A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals. AB - BACKGROUND: Ebola virus (EBOV) caused more than 11,000 deaths during the 2013 2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. METHODOLOGY/PRINCIPLE FINDINGS: Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. CONCLUSION/SIGNIFICANCE: Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development. PMID- 29795570 TI - Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population. AB - As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10-100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel contributing alleles, show evidence of association to CD. Independently, we find that genomewide common variant risk defined by GWAS shows a strong difference between AJ and non-AJ European control population samples (0.97 s.d. higher, p<10-16). Taken together, the results suggest coordinated selection in AJ population for higher CD risk alleles in general. The results and approach illustrate the value of exome sequencing data in case-control studies along with reference data sets like ExAC (sites VCF available via FTP at ftp.broadinstitute.org/pub/ExAC_release/release0.3/) to pinpoint genetic variation that contributes to variable disease predisposition across populations. PMID- 29795573 TI - Altered levels of memory T cell subsets and common gammac cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment. AB - BACKGROUND: CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common gammac cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets. METHODS: To examine the major T cell subsets and their association with the common gammac cytokines, the absolute numbers of CD4+ and CD8+ naive, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth-uninfected (UN, n = 58) and in post treatment INF individuals. RESULTS: Ss infection is characterized by significantly increased absolute numbers of naive and decreased absolute numbers of central and effector memory CD4+ T cells in comparison to UN individuals. No significant difference in the numbers of CD8+ T cell subsets was observed between the groups. The numbers of naive cells and central memory CD4+ T cells were significantly reversed after anthelmintic treatment. Circulating levels of IL-2, IL-7 and IL-15 were significantly diminished, whereas the levels of IL-4 and IL-9 were significantly increased in INF compared to UN individuals. Following anthelminthic treatment, IL-2, IL-7 and IL-15 levels were significantly increased, while IL-4 and IL-9 levels were significantly decreased. Our data also showed a significant positive correlation between the levels of IL-7 and the numbers of central and effector memory CD4+ T cells. CONCLUSION: Ss infection is characterized by alterations in the absolute numbers of CD4+ T cell subsets and altered levels of common gammac cytokines IL-2, IL-4, IL-7, IL-9 and IL-15; alterations which are partially reversed after anthelmintic treatment. PMID- 29795575 TI - A multi-level model of emerging technology: An empirical study of the evolution of biotechnology from 1976 to 2003. AB - In this paper, we develop an ecological, multi-level model that can be used to study the evolution of emerging technology. More specifically, by defining technology as a system composed of a set of interacting components, we can build upon the argument of multi-level density dependence from organizational ecology to develop a distribution-independent model of technological evolution. This allows us to distinguish between different stages of component development, which provides more insight into the emergence of stable component configurations, or dominant designs. We validate our hypotheses in the biotechnology industry by using patent data from the USPTO from 1976 to 2003. PMID- 29795577 TI - A keyword searchable attribute-based encryption scheme with attribute update for cloud storage. AB - Ciphertext-policy attribute-based encryption (CP-ABE) scheme is a new type of data encryption primitive, which is very suitable for data cloud storage for its fine-grained access control. Keyword-based searchable encryption scheme enables users to quickly find interesting data stored in the cloud server without revealing any information of the searched keywords. In this work, we provide a keyword searchable attribute-based encryption scheme with attribute update for cloud storage, which is a combination of attribute-based encryption scheme and keyword searchable encryption scheme. The new scheme supports the user's attribute update, especially in our new scheme when a user's attribute need to be updated, only the user's secret key related with the attribute need to be updated, while other user's secret key and the ciphertexts related with this attribute need not to be updated with the help of the cloud server. In addition, we outsource the operation with high computation cost to cloud server to reduce the user's computational burden. Moreover, our scheme is proven to be semantic security against chosen ciphertext-policy and chosen plaintext attack in the general bilinear group model. And our scheme is also proven to be semantic security against chosen keyword attack under bilinear Diffie-Hellman (BDH) assumption. PMID- 29795574 TI - Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function. AB - HIV infection has been associated with increased diabetes risk, but prior work has mostly focused on insulin resistance, as opposed to beta cell effects, or included patients on antiretroviral therapies (ART) directly linked to metabolic toxicity. In this analysis, we measured markers of glucose homeostasis and beta cell function, stress, and death in fasting sera from a cross section of HIV+ individuals off ART (n = 43), HIV+ individuals on ART (n = 23), and HIV- controls (n = 39). Markers included glucose, HOMA%S, HOMA%B, proinsulin:C-peptide ratio (PI:C ratio), and circulating preproinsulin (INS) DNA. We performed multiple linear regressions with adjustments for age, sex, race, BMI, and smoking status. Compared to HIV- controls, HIV+ participants off ART exhibited similar beta cell function and insulin sensitivity, without increases in markers of beta cell stress or death. Specifically, in HIV+ participants with CD4 counts <350 cells/MUL, PI:C ratios were lower than in HIV- controls (p<0.01), suggesting a reduction in intrinsic beta cell stress among this group. By contrast, HIV+ participants on ART had higher fasting glucose (p<0.0001) and lower HOMA%B (p<0.001) compared to HIV- controls. Among the entire HIV+ population, higher HIV RNA correlated with lower fasting glucose (r = -0.57, p<0.001), higher HOMA%B (r = 0.40, p = 0.001), and lower PI:C ratios (r = -0.42, p<0.001), whereas higher CD4 counts correlated with higher PI:C ratios (r = 0.2, p = 0.00499). Our results suggest that HIV seropositivity in the absence of ART does not worsen beta cell function or glucose homeostasis, but immune reconstitution with ART may be associated with worsened beta cell function. PMID- 29795576 TI - A method for age-matched OCT angiography deviation mapping in the assessment of disease- related changes to the radial peripapillary capillaries. AB - PURPOSE: To present a method for age-matched deviation mapping in the assessment of disease-related changes to the radial peripapillary capillaries (RPCs). METHODS: We reviewed 4.5x4.5mm en face peripapillary OCT-A scans of 133 healthy control eyes (133 subjects, mean 41.5 yrs, range 11-82 yrs) and 4 eyes with distinct retinal pathologies, obtained using spectral-domain optical coherence tomography angiography. Statistical analysis was performed to evaluate the impact of age on RPC perfusion densities. RPC density group mean and standard deviation maps were generated for each decade of life. Deviation maps were created for the diseased eyes based on these maps. Large peripapillary vessel (LPV; noncapillary vessel) perfusion density was also studied for impact of age. RESULTS: Average healthy RPC density was 42.5+/-1.47%. ANOVA and pairwise Tukey-Kramer tests showed that RPC density in the >=60yr group was significantly lower compared to RPC density in all younger decades of life (p<0.01). Average healthy LPV density was 21.5+/-3.07%. Linear regression models indicated that LPV density decreased with age, however ANOVA and pairwise Tukey-Kramer tests did not reach statistical significance. Deviation mapping enabled us to quantitatively and visually elucidate the significance of RPC density changes in disease. CONCLUSIONS: It is important to consider changes that occur with aging when analyzing RPC and LPV density changes in disease. RPC density, coupled with age-matched deviation mapping techniques, represents a potentially clinically useful method in detecting changes to peripapillary perfusion in disease. PMID- 29795578 TI - Public reaction to Chikungunya outbreaks in Italy-Insights from an extensive novel data streams-based structural equation modeling analysis. AB - The recent outbreak of Chikungunya virus in Italy represents a serious public health concern, which is attracting media coverage and generating public interest in terms of Internet searches and social media interactions. Here, we sought to assess the Chikungunya-related digital behavior and the interplay between epidemiological figures and novel data streams traffic. Reaction to the recent outbreak was analyzed in terms of Google Trends, Google News and Twitter traffic, Wikipedia visits and edits, and PubMed articles, exploiting structural modelling equations. A total of 233,678 page-views and 150 edits on the Italian Wikipedia page, 3,702 tweets, 149 scholarly articles, and 3,073 news articles were retrieved. The relationship between overall Chikungunya cases, as well as autochthonous cases, and tweets production was found to be fully mediated by Chikungunya-related web searches. However, in the allochthonous/imported cases model, tweet production was not found to be significantly mediated by epidemiological figures, with web searches still significantly mediating tweet production. Inconsistent relationships were detected in mediation models involving Wikipedia usage as a mediator variable. Similarly, the effect between news consumption and tweets production was suppressed by the Wikipedia usage. A further inconsistent mediation was found in the case of the effect between Wikipedia usage and tweets production, with web searches as a mediator variable. When adjusting for the Internet penetration index, similar findings could be obtained, with the important exception that in the adjusted model the relationship between GN and Twitter was found to be partially mediated by Wikipedia usage. Furthermore, the link between Wikipedia usage and PubMed/MEDLINE was fully mediated by GN, differently from what was found in the unadjusted model. In conclusion-a significant public reaction to the current Chikungunya outbreak was documented. Health authorities should be aware of this, recognizing the role of new technologies for collecting public concerns and replying to them, disseminating awareness and avoid misleading information. PMID- 29795579 TI - The South African Rea Phela Health Study: A randomized controlled trial of communication retention strategies. AB - Epidemiological transitions are occurring throughout Africa. To inform public health programs and policies, longitudinal cohorts investigating non-communicable diseases are needed. However, loss-to-follow up is a major problem. In preparation for a longitudinal study, we conducted a randomized controlled trial to test communication-based retention strategies (message content and delivery methods) among a pilot cohort of South African healthcare workers (n = 1536; median age = 36; women = 1270). Two messaging formats across three delivery modes were tested. Response rates were analyzed by intervention, survey return date and method using chi-square tests and univariate logistic regression. Sixty-seven of 238 (17.4%) control group participants and 238 of 1152 (24.6%) intervention group participants were retained (OR 1.54: CI 1.15-2.07; P = 0.004). Odds of being retained were 1.68 times greater for participants who received regular contact and themed messages compared to control (CI 1.22-2.32; P = 0.001). Neither health status nor clinical condition affected response rates (P>0.05). Time-to-first contact did not impact response rates (P>0.05). Message content and delivery method influenced response rates compared to the control, however no difference was found between intervention groups. Although greater retention is required for valid cohort studies, these findings are the first to quantitatively assess retention factors in Africa. PMID- 29795580 TI - The impact of conjunctival flap method and drainage cannula diameter on bleb survival in the rabbit model. AB - PURPOSE: To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS). METHODS: Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based conjunctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26 gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. Filtration blebs were evaluated every three days by a masked observer. Bleb failure was defined as the primary endpoint in this study and was recorded after two consecutive flat bleb evaluations. RESULTS: Group 1 (LBCF, 22- gauge cannula) had a mean bleb survival time (Mean +/- SD) of 18.7 +/- 2.9 days. Group 2 (LBCF, 26-gauge cannula) also had a mean bleb survival time of 18.7 +/- 2.9 days. Group 3 (FBCF, 22-gauge cannula) had a mean bleb survival time of 19.2 +/- 3.8 days. Group 4 (FBCF, 26-gauge cannula) had a mean bleb survival time of 19.7 +/- 4.1 days. A 2-way analysis of variance showed that neither surgical approach nor cannula gauge made a statistically significant difference in bleb survival time (P = 0.634 and P = 0.874). Additionally, there was no significant interaction between cannula gauge and conjunctival flap approach (P = 0.874), suggesting that there was not a combination of drainage gauge and conjunctival flap method that produced superior bleb survival. CONCLUSION: Limbus and fornix-based conjunctival flaps are equally effective in promoting bleb survival using both 22 and 26-gauge cannulas in the rabbit model. The 26-gauge drainage tube may be preferred because its smaller size facilitates the implantation process, reducing the risk of corneal contact. PMID- 29795581 TI - High-throughput adaptive sampling for whole-slide histopathology image analysis (HASHI) via convolutional neural networks: Application to invasive breast cancer detection. AB - Precise detection of invasive cancer on whole-slide images (WSI) is a critical first step in digital pathology tasks of diagnosis and grading. Convolutional neural network (CNN) is the most popular representation learning method for computer vision tasks, which have been successfully applied in digital pathology, including tumor and mitosis detection. However, CNNs are typically only tenable with relatively small image sizes (200 * 200 pixels). Only recently, Fully convolutional networks (FCN) are able to deal with larger image sizes (500 * 500 pixels) for semantic segmentation. Hence, the direct application of CNNs to WSI is not computationally feasible because for a WSI, a CNN would require billions or trillions of parameters. To alleviate this issue, this paper presents a novel method, High-throughput Adaptive Sampling for whole-slide Histopathology Image analysis (HASHI), which involves: i) a new efficient adaptive sampling method based on probability gradient and quasi-Monte Carlo sampling, and, ii) a powerful representation learning classifier based on CNNs. We applied HASHI to automated detection of invasive breast cancer on WSI. HASHI was trained and validated using three different data cohorts involving near 500 cases and then independently tested on 195 studies from The Cancer Genome Atlas. The results show that (1) the adaptive sampling method is an effective strategy to deal with WSI without compromising prediction accuracy by obtaining comparative results of a dense sampling (~6 million of samples in 24 hours) with far fewer samples (~2,000 samples in 1 minute), and (2) on an independent test dataset, HASHI is effective and robust to data from multiple sites, scanners, and platforms, achieving an average Dice coefficient of 76%. PMID- 29795582 TI - PKR modulates abnormal brain signaling in experimental obesity. AB - Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer's disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome ("metaflammasome") mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome. In wild type (WT) and PKR-/- mice, blood glucose, insulin and lipid levels and the brain expression of the phosphorylated components of the metaflammasome-PKR, JNK, IRS1 and IKKbeta-were studied after the induction of obesity by a high fat diet (HFD). The results showed significant increased levels of activated brain metaflammasome proteins in exposed WT mice but the changes were not significant in PKR-/- mice. In addition, gain weight was observed in WT mice and also in PKR-/- mice exposed to HFD. Increased blood insulin level was more accentuated in PKR -/- mice. The modulation of PKR activity could be an appropriate therapeutic approach, aimed at reducing abnormal brain metabolism and inflammation linked to metabolic disorders in order to reduce the risk of neurodegeneration. PMID- 29795583 TI - Manganese-porphyrin-enhanced MRI for the detection of cancer cells: A quantitative in vitro investigation with multiple clinical subtypes of breast cancer. AB - Magnetic resonance imaging (MRI) contrast agents (CAs) are chemical compounds that can enhance image contrast on T1- or T2- weighted MR image. We have previously demonstrated the potential of MnCl2, a manganese-based CA, in cellular imaging of breast cancer using T1-weighted MRI. In this work, we examined the potential of another class of manganese-based CAs, manganese porphyrins (MnPs), for sensitive cellular detection of multiple clinical subtypes of breast cancer using quantitative MRI. Using a clinical 3.0-T MRI scanner, the relaxivities of two MnPs, MnTPPS4 and MnTPPS3NH2, and conventional Gd-DTPA (control) were measured in ultrapure water and their T1 contrast enhancement patterns were characterized in multiple clinical subtypes of breast cancer. The toxicity of the three CAs was evaluated in vitro. Compared to Gd-DTPA, both MnTPPS3NH2 and MnTPPS4 enabled a more sensitive multi-subtype detection of four breast cell lines at doses that posed no cytotoxic effects, with MnTPPS3NH2 producing the greatest positive enhancement. The superior T1 enhancement capabilities of MnPs over Gd-DTPA are statistically significant and are likely due to their greater cellular uptake and relaxivities. The results demonstrate that multiple clinical subtypes of breast cancer can be imaged on a 3.0-T MRI scanner using MnPs as T1 cellular CAs. PMID- 29795584 TI - A return to the genetic heritage of durum wheat to cope with drought heightened by climate change. AB - The objective of this work was to perform a comparative analysis of the physiological, biochemical and agronomical parameters of recent and heritage durum wheat cultivars (Triticum durum Desf.) under water-deficit conditions. Five cultivars were grown under irrigated (control) and rainfall (stressed) conditions. Different agro-physiological and biochemical parameters were studied: electrolyte leakage, relative water content, chlorophyll fluorescence, proline, soluble sugars, specific peroxidase activity, yield and drought stress indices. It was revealed that a water deficit increased proline content, electrolyte leakage, soluble sugars and specific peroxidase activity and decreased relative water content, fluorescence and grain yield. According to these parameters and drought stress indices, our investigation indicated that old cultivars are the best-adapted to local conditions and showed characteristics of drought tolerance, while recent cultivars showed more drought susceptibility. Therefore, local cultivars of each country should be kept by farmers and plant breeders to preserve their genetic heritage. PMID- 29795585 TI - Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas. AB - Group C serogroup includes members of the Orthobunyavirus genus (family Peribunyaviridae) and comprises 15 arboviruses that can be associated with febrile illness in humans. Although previous studies described the genome characterization of Group C orthobunyavirus, there is a gap in genomic information about the other viruses in this group. Therefore, in this study, complete genomes of members of Group C serogroup were sequenced or re-sequenced and used for genetic characterization, as well as to understand their phylogenetic and evolutionary aspects. Thus, our study reported the genomes of three new members in Group C virus (Apeu strain BeAn848, Itaqui strain BeAn12797 and Nepuyo strain BeAn10709), as well as re-sequencing of original strains of five members: Caraparu (strain BeAn3994), Madrid (strain BT4075), Murucutu (strain BeAn974), Oriboca (strain BeAn17), and Marituba (strain BeAn15). These viruses presented a typical genomic organization related to members of the Orthobunyavirus genus. Interestingly, all viruses of this serogroup showed an open reading frame (ORF) that encodes the putative nonstructural NSs protein that precedes the nucleoprotein ORF, an unprecedented fact in Group C virus. Also, we confirmed the presence of natural reassortment events. This study expands the genomic information of Group C viruses, as well as revalidates the genomic organization of viruses that were previously reported. PMID- 29795586 TI - Estimating comparable English healthcare costs for multiple diseases and unrelated future costs for use in health and public health economic modelling. AB - OBJECTIVES: Healthcare interventions, and particularly those in public health may affect multiple diseases and significantly prolong life. No consensus currently exists for how to estimate comparable healthcare costs across multiple diseases for use in health and public health cost-effectiveness models. We aim to describe a method for estimating comparable disease specific English healthcare costs as well as future healthcare costs from diseases unrelated to those modelled. METHODS: We use routine national datasets including programme budgeting data and cost curves from NHS England to estimate annual per person costs for diseases included in the PRIMEtime model as well as age and sex specific costs due to unrelated diseases. RESULTS: The 2013/14 annual cost to NHS England per prevalent case varied between L3,074 for pancreatic cancer and L314 for liver disease. Costs due to unrelated diseases increase with age except for a secondary peak at 30-34 years for women reflecting maternity resource use. CONCLUSIONS: The methodology described allows health and public health economic modellers to estimate comparable English healthcare costs for multiple diseases. This facilitates the direct comparison of different health and public health interventions enabling better decision making. PMID- 29795588 TI - The optimal sampling design for littoral habitats modelling: A case study from the north-western Mediterranean. AB - Species distribution models (SDMs) have been used to predict potential distributions of habitats and to model the effects of environmental changes. Despite their usefulness, currently there is no standardized sampling strategy that provides suitable and sufficiently representative predictive models for littoral marine benthic habitats. Here we aim to establish the best performing and most cost-effective sample design to predict the distribution of littoral habitats in unexplored areas. We also study how environmental variability, sample size, and habitat prevalence may influence the accuracy and performance of spatial predictions. For first time, a large database of littoral habitats (16,098 points over 562,895 km of coastline) is used to build up, evaluate, and validate logistic predictive models according to a variety of sampling strategies. A regularly interspaced strategy with a sample of 20% of the coastline provided the best compromise between usefulness (in terms of sampling cost and effort) and accuracy. However, model performance was strongly depen upon habitat characteristics. The proposed sampling strategy may help to predict the presence or absence of target species or habitats thus improving extensive cartographies, detect high biodiversity areas, and, lastly, develop (the best) environmental management plans, especially in littoral environments. PMID- 29795587 TI - Incidence of influenza A(H3N2) virus infections in Hong Kong in a longitudinal sero-epidemiological study, 2009-2015. AB - BACKGROUND: Many serologic studies were done during and after the 2009 influenza pandemic, to estimate the cumulative incidence of influenza A(H1N1)pdm09 virus infections, but there are few comparative estimates of the incidence of influenza A(H3N2) virus infections during epidemics. METHODS: We conducted a longitudinal serologic study in Hong Kong. We collected sera annually and tested samples from 2009-13 by HAI against the A/Perth/16/2009(H3N2) virus, and samples from 2013-15 against the A/Victoria/361/2011(H3N2) virus using the hemagglutination inhibition (HAI) assay. We estimated the cumulative incidence of infections based on 4-fold or greater rises in HAI titers in consecutive sera. RESULTS: There were four major H3N2 epidemics: (1) Aug-Oct 2010; (2) Mar-Jun 2012; (3) Jul-Oct 2013; and (4) Jun-Jul 2014. Between 516 and 619 relevant pairs of sera were available for each epidemic. We estimated that 9%, 19%, 7% and 7% of the population were infected in each epidemic, respectively, with higher incidence in children in epidemics 1 and 4. CONCLUSIONS: We found that re-infections in each of the four H3N2 epidemics that occurred from 2010 through 2014 were rare. The largest H3N2 epidemic occurred with the lowest level of pre-epidemic immunity. PMID- 29795589 TI - Visceral leishmaniasis in selected communities of Hamar and Banna-Tsamai districts in Lower Omo Valley, South West Ethiopia: Sero-epidemological and Leishmanin Skin Test Surveys. AB - BACKGROUND: Visceral leishmaniasis [VL] is a debilitating parasitic disease which invariably kills untreated patients. The disease is caused by Leishmania (L.) donovani or L. infantum, and transmitted by the bite of female phlebotomine sandflies. VL often remains subclinical but can become symptomatic with an acute/subacute or chronic course. Globally, the Eastern Africa region is one of the main VL endemic areas. The disease is prevalent in numerous foci within Eritrea, Ethiopia, Kenya, Somalia, Sudan South Sudan, and Uganda. In Ethiopia, the Lower Omo plain is one of the many VL endemic regions. OBJECTIVES: The objective of this study was to determine the prevalence of asymptomatic visceral leishmaniasisin Hamar and Banna-Tsamai districts of the South Omo plains where VL is becoming an emerging health problem of neglected communities. METHODS: A community based cross-sectional survey was conducted in 2013 between 25th of July and 14th of August. A total of 1682 individuals living in 404 households were included in the study. Socio-demographic and clinical data were collected from each of the participants and venous blood was also collected for the detection of antibodies to visceral leishmaniasis using Direct Agglutination Test. Leishmanin Skin Test was performed to detect the exposure to the parasite. RESULTS: The surveys included 14 villages located in areas where VL had been reported. In a study population of 1682 individuals, the overall positive leishmanian skin test and sero-prevalence rates respectively were 8.6% and 1.8%. A statistically significant variation in the rate of positive LST response was observed in different study sites and age groups. Positive LST response showed an increasing trend with age. The sero-prevalence rate also showed a statistically significant variation among different study sites. Higher rates of sero-prevalence were observed in children and adolescents. The LST and sero-prevalence rates in Hamar District exceeded significantly that of Banna-Tsamai District (10.7% versus 5.8% for LST; and 2.6% versus 0.7% for sero-prevalence). CONCLUSION: The prevalence of asymptomatic VL infection in Hamar and Banna-Tsamai districts during the study period in 2013 was low compared to rates previously reported in other endemic areas of Ethiopia. This could be due to the fact that the disease is emerging in Hamar and Banna-Tsamai districts. Based on records of a nearby Hospital, increasing numbers of active VL cases have been reported in these districts through the years 2006-2012, especially in Hamar District. Both districts are important destinations of tourism, and thus the importance of surveillance should be emphasized. Detailed epidemiological and entomological studies are recommended. PMID- 29795590 TI - Intramuscular fat is present in cervical multifidus but not soleus in patients with chronic whiplash associated disorders. AB - The presence of intramuscular fat (IMF) in the cervical spine muscles of patients with whiplash associated disorders (WAD) has been consistently found. The mechanisms underlying IMF are not clear but preliminary evidence implicates a relationship with stress system responses. We hypothesised that if systemic stress system responses do play a role then IMF would be present in muscles remote to the cervical spine. We aimed to investigate if IMF are present in muscle tissue remote (soleus) to the cervical spine in people with chronic WAD. A secondary aim was to investigate associations between IMF and posttraumatic stress symptom levels. Forty-three people with chronic WAD (25 female) and 16 asymptomatic control participants (11 female) participated. Measures of pain, disability and posttraumatic stress symptoms were collected from the WAD participants. Both groups underwent MRI measures of IMF in cervical multifidus and the right soleus muscle. There was significantly greater IMF in cervical multifidus in patients with WAD and moderate/severe disability compared to controls (p = 0.009). There was no difference in multifidus IMF between the mild and moderate/severe disability WAD groups (p = 0.64), or the control and mild WAD groups (p = 0.21). IMF in the right soleus was not different between the groups (p = 0.47). In the WAD group, we found no correlation between PDS symptoms and cervical multifidus IMF or between PDS symptoms and soleus IMF. Global differences in IMF are not a feature of chronic WAD, with differences in IMF limited to the cervical spine musculature. While the mechanisms for the development of IMF in the cervical spine following whiplash injury remain unclear, our data indicate that local factors more likely contribute to these differences. PMID- 29795591 TI - Benefits of biodiverse marine resources to child nutrition in differing developmental contexts in Hispaniola. AB - There is an urgent need for an improved empirical understanding of the relationship among biodiverse marine resources, human health and development outcomes. Coral reefs are often at this intersection for developing nations in the tropics-an ecosystem targeted for biodiversity conservation and one that provides sustenance and livelihoods for many coastal communities. To explore these relationships, we use the comparative development contexts of Haiti and the Dominican Republic on the island of Hispaniola. We combine child nutrition data from the Demographic Health Survey with coastal proximity and coral reef habitat diversity, and condition to empirically test human benefits of marine natural resources in differing development contexts. Our results indicate that coastal children have a reduced likelihood of severe stunting in Haiti but have increased likelihoods of stunting and reduced dietary diversity in the Dominican Republic. These contrasting results are likely due to the differential in developed infrastructure and market access. Our analyses did not demonstrate an association between more diverse and less degraded coral reefs and better childhood nutrition. The results highlight the complexities of modelling interactions between the health of humans and natural systems, and indicate the next steps needed to support integrated development programming. PMID- 29795592 TI - Dissolution and uniformity of content of tablets developed with extract of Ximenia americana L. AB - Herbal medicines currently represent an important part of the world pharmaceutical market, which shows growing interest in the use of herbal medicines. However, the production of such medicines involves a complex series of steps, which determine the production viability and the quality of the final product. Ximenia americana L. is a plant occurring in several regions of the world, with well-known and applied medicinal properties. Thus, the aim of this work was to develop and evaluate the physical and physical-chemical quality of tablets produced with X. americana L. extract. The extract was spray-dried from a hydroethanolic extractive solution and characterized as to its phytochemical composition. The chemical marker was determined and quantified using validated chromatographic methods. These methods indicated the presence of gallic acid at a concentration of 1.61 mg g(-1). Formulations were proposed and analyzed for their flow and compaction properties. The best formulation was used to obtain a batch of tablets, which was evaluated for its quality characteristics and showed to be within the pharmacopoeial specifications for average weight, hardness, friability, and disintegration time. The dissolution profile of the tablets produced was obtained, showing the release of about 70% of the vegetable extract content within 30 minutes. Results showed that it was possible to obtain herbal tablets containing a high content of vegetal extract by direct compression, developing a rapid process of formulation and production and guaranteeing the quality characteristics of the final product. PMID- 29795593 TI - Use of evidential reasoning and AHP to assess regional industrial safety. AB - China's fast economic growth contributes to the rapid development of its urbanization process, and also renders a series of industrial accidents, which often cause loss of life, damage to property and environment, thus requiring the associated risk analysis and safety control measures to be implemented in advance. However, incompleteness of historical failure data before the occurrence of accidents makes it difficult to use traditional risk analysis approaches such as probabilistic risk analysis in many cases. This paper aims to develop a new methodology capable of assessing regional industrial safety (RIS) in an uncertain environment. A hierarchical structure for modelling the risks influencing RIS is first constructed. The hybrid of evidential reasoning (ER) and Analytical Hierarchy Process (AHP) is then used to assess the risks in a complementary way, in which AHP is hired to evaluate the weight of each risk factor and ER is employed to synthesise the safety evaluations of the investigated region(s) against the risk factors from the bottom to the top level in the hierarchy. The successful application of the hybrid approach in a real case analysis of RIS in several major districts of Beijing (capital of China) demonstrates its feasibility as well as provides risk analysts and safety engineers with useful insights on effective solutions to comprehensive risk assessment of RIS in metropolitan cities. The contribution of this paper is made by the findings on the comparison of risk levels of RIS at different regions against various risk factors so that best practices from the good performer(s) can be used to improve the safety of the others. PMID- 29795595 TI - Long-term treatment outcomes of intermittent androgen deprivation therapy for relapsed prostate cancer after radical prostatectomy. AB - PURPOSE: Intermittent androgen deprivation therapy is an effective treatment for metastatic prostate cancer. However, no study to date has evaluated the long-term outcomes of this treatment among patients with prostate cancer after radical prostatectomy. We retrospectively examined the treatment outcomes of patients with prostate-specific antigen recurrence who underwent radical prostatectomy at our department. MATERIALS AND METHODS: Of the 690 patients who underwent radical prostatectomy for local prostate cancer between 1988 and 2011, 129 patients who received androgen deprivation therapy for prostate-specific antigen recurrence were included in this study. Patient characteristics, luteinizing hormone releasing hormone agonist administration, and outcomes were compared between the intermittent androgen deprivation group (n = 66) and the continuous androgen deprivation therapy group (n = 63). The non-recurrence and overall survival rates were compared between groups. RESULTS: Thirty-six patients (27.9%) experienced recurrence after luteinizing hormone-releasing hormone agonist administration. The 5-year non-recurrence rate and 10-year overall survival rate were higher in the intermittent group (92.9%) than in the continuous group (92.9 vs 57.9%, P < 0.001; and 95.9% vs 84.3%, P = 0.047, respectively). Furthermore, 63 patients (48.8%) showed a PSA nadir of less than 0.01 ng/mL after initiation of luteinizing hormone-releasing hormone agonist; among these patients, the non recurrence rate was significantly higher in the intermittent androgen deprivation group (P = 0.003). CONCLUSIONS: Intermittent androgen deprivation therapy for prostate specific antigen recurrence after radical prostatectomy contributed to improvement of the non-recurrence rate and overall survival, and can be considered an effective therapy for better prognosis. PMID- 29795594 TI - Cell electrofusion based on nanosecond/microsecond pulsed electric fields. AB - Traditionally, microsecond pulsed electric field was widely used in cell electrofusion technology. However, it was difficult to fuse the cells with different sizes. Because the effect of electroporation based on microsecond pulses was greatly influenced by cell sizes. It had been reported that the differences between cell sizes can be ignored when cells were exposed to nanosecond pulses. However, pores induced by those short nanosecond pulses tended to be very small (0.9 nm) and the pores were more easy to recover. In this work, a finite element method was used to simulate the distribution, radius and density of the pores. The innovative idea of "cell electrofusion based on nanosecond/microsecond pulses" was proposed in order to combine the advantages of nanosecond pulses and microsecond pulses. The model consisted of two contact cells with different sizes. Three kinds of pulsed electric fields were made up of two 100-ns, 10-kV/cm pulses; two 10-MUs, 1-kV/cm pulses; and a sequence of a 100 ns, 10-kV/cm pulse, followed by a 10-MUs, 1-kV/cm pulse. Some obvious advantageous can be found when nanosecond/microsecond pulses were considered. The pore radius was large enough (70nm) and density was high (5*1013m-2) in the cell junction area. Moreover, pores in the non-contact area of the cell membrane were small (1-10 nm) and sparse (109-1012m-2). Areas where the transmembrane voltage was higher than 1V were only concentrated in the cell junction. The transmembrane voltage of other areas were at most 0.6V when we tested the rest of the cell membrane. Cell fusion efficiency can be improved remarkably because electroporation was concentrated in the cell contact area. PMID- 29795596 TI - Evaluation of tracer labelled methionine load test in vitamin B-12 deficient adolescent women. AB - BACKGROUND: Methionine loading test (MLT) has been used primarily to identify defects in transsulfuration of homocysteine in cystathionine beta synthase deficiency. It may not be as useful to evaluate remethylation pathway, in vitamin B-12 and folate deficiencies. OBJECTIVE: We used tracer isotope labelled MLT to interrogate transsulfuration and remethylation independently in vitamin B-12 deficiency. DESIGN: We studied vitamin B-12 deficient women with a tracer labelled MLT before and eleven months after treatment with vitamin B-12. The fractional contribution of [13C]homocysteine to breath CO2 was used as a measure of transsulfuration, and difference in the intracellular enrichment of [13C]methionine and that of [C2H3]methionine as a measure of remethylation of homocysteine. Combined pre- and post-treatment results were analyzed to investigate the association between plasma vitamin B-12 concentrations and measures of homocysteine metabolism. RESULTS: The subjects were 17 years old, with a BMI of 19.4 kg/m2. Treatment with vitamin B-12, 2ug/day increased plasma B 12 from 93 (78.7, 106.2) [median (25th, 75th centiles)] to 161.5 (125.5, 226.2) pmol/L; 44% were below <150pmol/L after treatment. Fasting homocysteine concentration was significantly lower and that of cysteine higher in subjects with B-12 levels >150pmol/L. The tracer estimated transsulfuration of homocysteine was lower and remethylation higher with B-12 levels >150pmol/L when compared with those <150pmol/L. CONCLUSIONS: The tracer labelled MLT in combination with fasting parameters is a robust way to estimate parameters of methionine metabolism and can be used in the field where prime-constant rate infusion studies cannot be done efficiently. PMID- 29795597 TI - Antibacterial Effect of (2E,2E)-4,4-Trisulfanediylbis(but-2-enoic acid) against Staphylococcus aureus. AB - A new highly active molecule, (2E, 2E)-4,4-trisulfanediylbis(but-2-enoic acid) (TSDB), was designed and synthesized through comparative molecular field analysis with the diallyl trisulfide structure of garlic. TSDB exerted a strong inhibitory effect against Staphylococcus aureus, with minimal inhibitory and minimal bactericidal concentrations of 16 and 128 MUg/mL, respectively. TSDB destructed the integrity of the S. aureus cell membrane but weakly damaged the bacterial cell wall. TSDB also increased the conductivity and protein expression in microbial broth but minimally influenced the level of extracellular alkaline phosphatase. TSDB could be a novel food preservative. PMID- 29795598 TI - A clinical nursing rotation transforms medical students' interprofessional attitudes. AB - This study explores the extent to which a one-week nursing rotation for medical students changed the interprofessional attitudes of the participating nurses and students. Third-year medical students worked with nurses before starting clinical rotations. Pre- and post-experience surveys assessing perceptions of mutual respect, nurse-doctor roles, and interprofessional communication and teamwork were given to 55 nurses and 57 students. The surveys consisted of qualitative questions and a Likert scale questionnaire that was analyzed using qualitative and quantitative content analyses. The response rate was 51/57 (89%) students and 44/55 (80%) nurse preceptors. Nurses reported that students met nurses' expectations by displaying responsibility, respect, effective communication, and an understanding of nursing roles. Medical students' narratives demonstrated two significant changes. First, their views of nurses changed from that of physician helpers to that of collaborative patient-centred professionals. Second, they began defining nursing not by its tasks, but as a caring- and communication centred profession. Responses to Likert-scaled questions showed significant differences corresponding to changes described in the narrative. A one-week immersive clinical nursing rotation for medical students was a transformative way of learning interprofessional competencies. Learning in an authentic workplace during a clinical rotation engendered mutual respect between nurses and future doctors. Students' view of the role of nurses changed from nurses working for doctors with patients, to working with doctors for patients. PMID- 29795599 TI - Connectivity and seasonality cause rapid taxonomic and functional trait succession within an invertebrate community after stream restoration. AB - General colonization concepts consent that a slow process of microhabitat formation and subsequent niche realization occurs during early stages after new habitat is released. Subsequently, only few species are able to colonize new habitat in the early onset of succession, while species richness increases steadily over time. Although most colonization studies have been performed in terrestrial ecosystems, running water ecosystems are equally or even more prone to colonization after disturbance due to their dynamic nature. We question how invertebrate succession patterns reconcile with general colonization concepts. With this study we provide insight into the colonization process in newly created lowland stream trajectories and answer how within-stream bio- and functional diversity develops over time. Our results show a rapid influx of species, with a wide range of functional traits, during the first season after water flow commenced. During more than two years of regular monitoring, immigration rates were highest in autumn, marking the effects of seasonality on invertebrate dispersal. Biodiversity increased while abundance peaks of species alternated between seasons. Moreover, also days since start of the experiment explains a considerable part of the variability for taxa as well as traits. However, the relative trait composition remained similar throughout the entire monitoring period and only few specific traits had significantly higher proportions during specific seasons. This indicates that first phase colonization in freshwater streams can be a very rapid process that results in a high biodiversity and a large variety of species functional characteristics from the early onset of succession, contradicting general terrestrial colonization theory. PMID- 29795600 TI - Incremental fuzzy C medoids clustering of time series data using dynamic time warping distance. AB - Clustering time series data is of great significance since it could extract meaningful statistics and other characteristics. Especially in biomedical engineering, outstanding clustering algorithms for time series may help improve the health level of people. Considering data scale and time shifts of time series, in this paper, we introduce two incremental fuzzy clustering algorithms based on a Dynamic Time Warping (DTW) distance. For recruiting Single-Pass and Online patterns, our algorithms could handle large-scale time series data by splitting it into a set of chunks which are processed sequentially. Besides, our algorithms select DTW to measure distance of pair-wise time series and encourage higher clustering accuracy because DTW could determine an optimal match between any two time series by stretching or compressing segments of temporal data. Our new algorithms are compared to some existing prominent incremental fuzzy clustering algorithms on 12 benchmark time series datasets. The experimental results show that the proposed approaches could yield high quality clusters and were better than all the competitors in terms of clustering accuracy. PMID- 29795601 TI - The complete chloroplast genome sequence of Actinidia arguta using the PacBio RS II platform. AB - Actinidia arguta is the most basal species in a phylogenetically and economically important genus in the family Actinidiaceae. To better understand the molecular basis of the Actinidia arguta chloroplast (cp), we sequenced the complete cp genome from A. arguta using Illumina and PacBio RS II sequencing technologies. The cp genome from A. arguta was 157,611 bp in length and composed of a pair of 24,232 bp inverted repeats (IRs) separated by a 20,463 bp small single copy region (SSC) and an 88,684 bp large single copy region (LSC). Overall, the cp genome contained 113 unique genes. The cp genomes from A. arguta and three other Actinidia species from GenBank were subjected to a comparative analysis. Indel mutation events and high frequencies of base substitution were identified, and the accD and ycf2 genes showed a high degree of variation within Actinidia. Forty seven simple sequence repeats (SSRs) and 155 repetitive structures were identified, further demonstrating the rapid evolution in Actinidia. The cp genome analysis and the identification of variable loci provide vital information for understanding the evolution and function of the chloroplast and for characterizing Actinidia population genetics. PMID- 29795602 TI - Inference comprehension in text reading: Performance of individuals with right- versus left-hemisphere lesions and the influence of cognitive functions. AB - BACKGROUND: Right-hemisphere lesions (RHL) may impair inference comprehension. However, comparative studies between left-hemisphere lesions (LHL) and RHL are rare, especially regarding reading comprehension. Moreover, further knowledge of the influence of cognition on inferential processing in this task is needed. OBJECTIVES: To compare the performance of patients with RHL and LHL on an inference reading comprehension task. We also aimed to analyze the effects of lesion site and to verify correlations between cognitive functions and performance on the task. METHODS: Seventy-five subjects were equally divided into the groups RHL, LHL, and control group (CG). The Implicit Management Test was used to evaluate inference comprehension. In this test, subjects read short written passages and subsequently answer five types of questions (explicit, logical, distractor, pragmatic, and other), which require different types of inferential reasoning. The cognitive functional domains of attention, memory, executive functions, language, and visuospatial abilities were assessed using the Cognitive Linguistic Quick Test (CLQT). RESULTS: The LHL and RHL groups presented difficulties in inferential comprehension in comparison with the CG. However, the RHL group presented lower scores than the LHL group on logical, pragmatic and other questions. A covariance analysis did not show any effect of lesion site within the hemispheres. Overall, all cognitive domains were correlated with all the types of questions from the inference test (especially logical, pragmatic, and other). Attention and visuospatial abilities affected the scores of both the RHL and LHL groups, and only memory influenced the performance of the RHL group. CONCLUSIONS: Lesions in either hemisphere may cause difficulties in making inferences during reading. However, processing more complex inferences was more difficult for patients with RHL than for those with LHL, which suggests that the right hemisphere plays an important role in tasks with higher comprehension demands. Cognition influences inferential processing during reading in brain injured subjects. PMID- 29795603 TI - Evaluation of a teacher training program to enhance executive functions in preschool children. AB - BACKGROUND: Executive functions (EFs) play a critical role in cognitive and social development. During preschool years, children show not only rapid improvement in their EFs, but also appear sensitive to developmentally appropriate interventions. AIM: EMIL is a training program for German preschool teachers that was developed and implemented to improve the EFs of preschoolers. The aim of the present study was to evaluate its effects on the EFs of children between three and six years old. METHOD: The teacher training (eight sessions, 28.5 hours) was implemented in four preschools. The EFs of children of the intervention group (n = 72, 32 girls, Mage = 48 months) and the control group of four other matched preschools (n = 61, 27 girls, Mage = 48 months) were tested before, during, and after the intervention using different measures assessing working memory, inhibitory control, and cognitive flexibility. RESULTS: The intervention group showed significant gains on three out of seven EF tests (behavioral inhibition, visual-spatial working memory, and combined EFs) compared to the control group. Post hoc analyses for children with low initial EFs scores revealed that participation in the intervention led to significant gains in inhibitory control, visual-spatial working memory, and phonological working memory as well as a marginally significant difference for combined EFs. However, effect sizes were rather small. CONCLUSION: The results suggest that teacher training can lead to significant improvements in preschooler's EFs. Although preliminary, the results could contribute to the discussion on how teacher training can facilitate the improvement of EFs in preschool children. PMID- 29795604 TI - Survival outcomes post percutaneous coronary intervention: Why the hype about stent type? Lessons from a healthcare system in India. AB - A prospective, multicenter study was initiated by the Government of Maharashtra, India, to determine predictors of long-term outcomes of percutaneous coronary intervention (PCI) for coronary artery disease, and to compare the effectiveness of drug-eluting stents (DESs) and bare-metal stents (BMSs) in patients undergoing PCI under government-funded insurance. The present analysis included 4595 patients managed between August 2012 and November 2016 at any of 110 participating centers. Using the classical multivariable regression and propensity-matching approach, we found age to be the most important predictor of 1-year mortality and target lesion revascularization at 1 year post-PCI. However, using machine learning methods to account for unmeasured confounders and bias in this large observational study, we determined total stent length and number of stents deployed as the most important predictors of 1-year survival, followed by age and employment status. The unadjusted death rates were 5.0% and 3.8% for the BMS and DES groups, respectively (p = 0.185, log-rank test). The rate of re hospitalization (p<0.001) and recurrence of unstable angina (p = 0.08) was significantly lower for DESs than for BMSs. Increased use of DES after 2015 (following establishment of a price cap on DESs) was associated with a sharp decrease in adjusted hazard ratios of DESs versus BMSs (from 0.94 in 2013 to 0.58 in 2016), suggesting that high price was limiting DES use in some high-risk patients. Since stented length and stent number were the most important predictors of survival outcomes, adopting an ischemia-guided revascularization strategy is expected to help improve outcomes and reduce procedural costs. In the elderly, PCI should be reserved for cases where the benefits outweigh the higher risk of the procedure. As unemployed patients had poorer long-term outcomes, we expect that implementation of a post-PCI cardiovascular rehabilitation program may improve long-term outcomes. PMID- 29795605 TI - Advance directives for future dementia can be modified by a brief video presentation on dementia care: An experimental study. AB - OBJECTIVES: To investigate whether life-sustaining measures in medical emergency situations are less accepted for an anticipated own future of living with dementia, and to test whether a resource-oriented, in contrast to a deficit oriented video about the same demented person, would increase the acceptance of such life-saving measures. DESIGN: Experimental study conducted between September 2012 and February 2013. SETTING: Community dwelling female volunteers living in the region of Bonn, Germany. PARTICIPANTS: 278 women aged 19 to 89 (mean age 53.4 years). INTERVENTION: Presentation of a video on dementia care focusing either on the deficits of a demented woman (negative framing), or focusing on the remaining resources (positive framing) of the same patient. MAIN OUTCOME MEASURES: Approval of life-sustaining treatments in five critical medical scenarios under the assumption of having comorbid dementia, before and after the presentation of the brief videos on care. RESULTS: At baseline, the acceptance of life-sustaining measures in critical medical situations was significantly lower in subjects anticipating their own future life with dementia. Participants watching the resource-oriented film on living with dementia had significantly higher post-film acceptance rates compared to those watching the deficit-oriented negatively framed film. This effect particularly emerges if brief and efficient life-saving interventions with a high likelihood of physical recovery are available (eg, antibiotic treatment for pneumonia). CONCLUSIONS: Anticipated decisions regarding life-sustaining measures are negatively influenced by the subjective imagination of living with dementia, which might be shaped by common, unquestioned stereotypes. This bias can be reduced by providing audio-visual information on living with dementia which is not only centred around cognitive and functional losses but also focuses on remaining resources and the apparent quality of life. This is particularly true if the medical threat can be treated efficiently. These findings have implications for the practice of formulating, revising, and supporting advance directives. PMID- 29795606 TI - The Super-Seniors Study: Phenotypic characterization of a healthy 85+ population. AB - BACKGROUND: To understand why some people live to advanced age in good health and others do not, it is important to study not only disease, but also long-term good health. The Super-Seniors Study aims to identify factors associated with healthy aging. METHODS: 480 healthy oldest-old 'Super-Seniors' aged 85 to 105 years and never diagnosed with cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease, were compared to 545 mid-life controls aged 41-54, who represent a group that is unselected for survival from late-life diseases. Health and lifestyle information, personal and family medical history, and blood samples were collected from all participants. Super-Seniors also underwent four geriatric tests. RESULTS: Super-Seniors showed high cognitive (Mini-Mental State Exam mean = 28.3) and functional capacity (Instrumental Activities of Daily Living Scale mean = 21.4), as well as high physical function (Timed Up and Go mean = 12.3 seconds) and low levels of depression (Geriatric Depression Scale mean = 1.5). Super-Seniors were less likely to be current smokers than controls, but the frequency of drinking alcohol was the same in both groups. Super-Seniors were more likely to have 4 or more offspring; controls were more likely to have no children. Female Super-Seniors had a mean age of last fertility 1.9 years older than controls, and were 2.3 times more likely to have had a child at >= 40 years. The parents of Super-Seniors had mean ages of deaths of 79.3 years for mothers, and 74.5 years for fathers, each exceeding the life expectancy for their era by a decade. CONCLUSIONS: Super-Seniors are cognitively and physically high functioning individuals who have evaded major age-related chronic diseases into old age, representing the approximately top 1% for healthspan. The familiality of long lifespan of the parents of Super-Seniors supports the hypothesis that heritable factors contribute to this desirable phenotype. PMID- 29795607 TI - Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammation. AB - In the present work, we aimed to study the effects of free and polybutylcyanoacrylate nanoparticle-bound thymulin on immune cell activity in mice with chronic inflammation. NF-kappaB, MAPK, and PKC-theta signaling pathway activity was assessed, alongside Hsp72, Hsp90-alpha, and TLR4 expression and levels of apoptosis. In addition, plasma cytokines and blood and brain melatonin and serotonin levels were measured. In mice treated with gradually raised doses of lipopolysaccharide, significant increases in the activity of the signaling pathways tested, heat-shock protein and TLR4 expression, lymphocyte apoptosis, and plasma proinflammatory cytokine levels were noted. Moreover, we observed significantly heightened serotonin concentrations in the plasma and especially the brains of mice with inflammation. In contrast, melatonin levels were reduced in the tissues examined, particularly so in the brain. Treatment of these mice with thymulin alleviated fever, reduced apoptosis, increased splenic cell number, and decreased cytokine production, Hsp72, Hsp90, and TLR4 expression, and the activity of the signaling pathways examined. In addition, thymulin partially restored brain and blood serotonin and melatonin levels. Thus, thymulin suppressed the proinflammatory response in LPS-treated mice, indicating the potential of thymulin co-therapy in the treatment of sepsis. Nanoparticle-bound thymulin was more effective in several respects. PMID- 29795608 TI - Small field models with gravitational wave signature supported by CMB data. AB - We study scale dependence of the cosmic microwave background (CMB) power spectrum in a class of small, single-field models of inflation which lead to a high value of the tensor to scalar ratio. The inflaton potentials that we consider are degree 5 polynomials, for which we precisely calculate the power spectrum, and extract the cosmological parameters: the scalar index ns, the running of the scalar index nrun and the tensor to scalar ratio r. We find that for non vanishing nrun and for r as small as r = 0.001, the precisely calculated values of ns and nrun deviate significantly from what the standard analytic treatment predicts. We study in detail, and discuss the probable reasons for such deviations. As such, all previously considered models (of this kind) are based upon inaccurate assumptions. We scan the possible values of potential parameters for which the cosmological parameters are within the allowed range by observations. The 5 parameter class is able to reproduce all of the allowed values of ns and nrun for values of r that are as high as 0.001. Subsequently this study at once refutes previous such models built using the analytical Stewart-Lyth term, and revives the small field brand, by building models that do yield an appreciable r while conforming to known CMB observables. PMID- 29795609 TI - Oyster aquaculture impacts Zostera marina epibiont community composition in Akkeshi-ko estuary, Japan. AB - Coastal fisheries are in decline worldwide, and aquaculture has become an increasingly popular way to meet seafood demand. While finfish aquaculture can have substantial adverse effects on coastal ecosystems due mostly to necessary feed inputs, bivalves graze on natural phytoplankton and are often considered for their positive ecosystem services. We conducted two independent studies to investigate the effects of long-line Crassostrea gigas oyster aquaculture on Zostera marina seagrass beds and associated epibiont communities in Akkeshi-ko estuary, Japan. Results from both studies yielded no evidence of an effect of oyster aquaculture on the morphology, density, or biomass of Z. marina, but significant differences were apparent in the epibiont community. Reference seagrass beds located away from aquaculture had higher seagrass epiphyte loads and higher abundances of amphipods. Conversely, seagrass beds below aquaculture lines had higher sessile polychaete biomass and higher isopod abundances. Our results suggest that the presence of oyster aquaculture may have indirect effects on seagrass by changing epibiont community composition and relative abundances of species. One proposed mechanism is that cultured oysters feed on epiphytic diatoms and epiphyte propagules before they can settle on the seagrass, which reduces epiphyte loads and influences subsequent faunal settlement. If carefully implemented and monitored, long-line oyster aquaculture may be a sustainable option to consider as bivalve aquaculture expands to meet global seafood demand, but further work is needed to fully assess and generalize the community-level effects on seagrass epibionts. PMID- 29795611 TI - Improving the quality of a collective signal in a consumer EEG headset. AB - This work focuses on the experimental data analysis of electroencephalography (EEG) data, in which multiple sensors are recording oscillatory voltage time series. The EEG data analyzed in this manuscript has been acquired using a low cost commercial headset, the Emotiv EPOC+. Our goal is to compare different techniques for the optimal estimation of collective rhythms from EEG data. To this end, a traditional method such as the principal component analysis (PCA) is compared to more recent approaches to extract a collective rhythm from phase synchronized data. Here, we extend the work by Schwabedal and Kantz (PRL 116, 104101 (2016)) evaluating the performance of the Kosambi-Hilbert torsion (KHT) method to extract a collective rhythm from multivariate oscillatory time series and compare it to results obtained from PCA. The KHT method takes advantage of the singular value decomposition algorithm and accounts for possible phase lags among different time series and allows to focus the analysis on a specific spectral band, optimally amplifying the signal-to-noise ratio of a common rhythm. We evaluate the performance of these methods for two particular sets of data: EEG data recorded with closed eyes and EEG data recorded while observing a screen flickering at 15 Hz. We found an improvement in the signal-to-noise ratio of the collective signal for the KHT over the PCA, particularly when random temporal shifts are added to the channels. PMID- 29795610 TI - Virus survey in populations of two subspecies of bent-winged bats (Miniopterus orianae bassanii and oceanensis) in south-eastern Australia reveals a high prevalence of diverse herpesviruses. AB - While bats are often viewed as carriers of infectious disease agents, little research has been conducted on the effects these potential pathogens may have on the bat populations themselves. The southern bent-winged bat (Miniopterus orianae bassanii) is a critically endangered subspecies endemic to south-eastern Australia. Population numbers of this bat have been declining for the past 50 years, but the reasons for this are unclear. As part of a larger study to determine if disease could be a contributing factor to this decline, 351 southern bent-winged bats from four locations were captured, and oral swabs were collected and tested for the presence of potentially pathogenic viruses. Results were compared with those obtained from 116 eastern bent-winged bats (Miniopterus orianae oceanensis) from three different locations. The eastern bent-winged bat is a related but more common and widespread subspecies whose geographical range overlaps partly with southern bent-winged bats. Herpesviruses were detected in bent-winged bats from all seven locations. At least six novel herpesviruses (five betaherpesviruses and one gammaherpesvirus) were identified. The prevalence of herpesvirus infection was higher in eastern bent-winged bats (44%, 51/116), compared to southern bent-winged bats (27%, 95/351), although this varied across the locations and sampling periods. Adenoviruses and a range of different RNA viruses (lyssaviruses, filoviruses, coronaviruses and henipaviruses) were also tested for but not detected. The detected herpesviruses did not appear to be associated with obvious ill health, and may thus not be playing a role in the population decline of the southern bent-winged bat. The detection of multiple novel herpesviruses at a high prevalence of infection is consistent with our understanding of bats as hosts to a rich diversity of viruses. PMID- 29795612 TI - Race and virulence characterization of Puccinia graminis f. sp. tritici in China. AB - Wheat stem rust was once the most destructive plant disease, but it has been largely controlled. However, to prevent future problems, the ongoing development of resistant wheat varieties requires knowledge of the changing virulence patterns for Pgt virulence of the fungus that causes wheat stem rust and the detection of new races. Surveys were conducted from 2013-2014 to determine the races of the Pgt present in China. Low levels of stem rust infections were found in China during this investigation and 11 Puccinia graminis f. sp. tritici (Pgt) samples were obtained. In addition, 22 Pgt samples collected from the alternate host (Berberis) were obtained and have been reported for the first time. Fifty three isolates were obtained from all samples. Four race groups, including 13 physiological races, were identified. They included the most prevalent races, 34C3MTGQM and 34C6MRGQM, with 13.2% predominance, followed by 34C0MRGQM at 11.3%. Six new races that were virulent against the resistance genes, Sr5 + Sr11, were found for the first time in China, namely 34C0MRGQM, 34C3MTGQM, 34C3MKGQM, 34C3MKGSM, 34C6MTGSM, and 34C6MRGQM, with a predominance of 11.3, 13.2, 9.4, 9.4, 1.9, and 13.2%, respectively. Most of the genes studied were ineffective against one or more of the tested isolates, except Sr9e, Sr21, Sr26, Sr31, Sr33, Sr38, Sr47, and SrTt3. Genes Sr35, SrTmp, Sr30, Sr37, Sr17, and Sr36 were effective in 92.5, 86.8, 84.9, 84.9, 79.3, and 77.4% of the tested isolates, respectively. In contrast, all of the isolates were virulent against Sr6, Sr7b, Sr9a, Sr9b, Sr9d, Sr9g, and SrMcN. Our results indicate that remarkable differences exist among the categories of the races in this study (i.e., their known virulence gene spectra) and the Pgt races reported previously. In addition, the sexual cycle of Pgt may contribute to its diversity in China. PMID- 29795613 TI - Dietary sodium butyrate improves intestinal development and function by modulating the microbial community in broilers. AB - This study investigated the effects of dietary sodium butyrate (SB) supplementation, provided as a specially coated product, on growth performance, intestinal development, morphological structure and function in broilers. In total, 720 one-day-old Arbor Acres male broilers were randomly allocated into six treatment groups with six replicates each and then fed basal diets (control) supplemented with 0, 200, 400, 800 or 1000 mg/kg of SB or with antibiotics (100 mg/kg aureomycin and 20 mg/kg colistin sulfate). The growth trial lasted for 42 days. No differences (P>0.05) in growth performance were detected between groups during the grower period (1-21 d) or over the total (1-42 d) trial period, whereas the addition of SB improved the intestinal structure by stimulating (P<0.05) goblet cells on jejunal and ileal villi accompanied by a trend towards increased (Pdiets<0.10) ileal villus height. In addition, more inerratic leaf shaped villi and mucus secretion and significantly fewer erosions were demonstrated by scanning electron microscopy. Apart from decreased (P<0.05) malondialdehyde (MDA) in the ileal mucosa at 21 d of age, supplemental SB at higher doses (800 mg/kg) led to greater (P<0.05) total antioxidant capacity and depressed (P<0.05) MDA concentrations in the jejunal mucosa. Birds fed with 400 mg/kg and 800 mg/kg SB had higher (P<0.05) acetic acid concentrations at 42 d and higher butyric acid at 21 d in the jejunum chyme. Morever, chicks fed SB diet were found to have higher concentrations of butyric acid (P<0.05) in the ileal chyme. SB additions at 400 mg/kg displayed higher Firmicutes and Proteobacteria levels, while a higher (P<0.05) relative abundance of Bacteroidetes was observed at 800 mg/kg. Furthermore, we found a striking decrease in Enterobacteriaceae and increases in Lachnospiraceae and Rikenellaceae in the cecal lumen of birds fed 800 mg/kg SB as well as a higher proportion of Ruminococcaceae and a noticeable reduction (P<0.05) of Lactobacillaceae in birds treated with 400 mg/kg SB. Taken together, our results support the importance of SB in improving the intestinal development, morphological structure and biological functions of broilers through modulation of the microbial community, which seems to be optimized for gut health at higher doses (800 mg/kg) of SB. PMID- 29795615 TI - Terrestrial mammal responses to oil palm dominated landscapes in Colombia. AB - The rapid expansion of oil palm cultivation in the Neotropics has generated great debate around possible biodiversity impacts. Colombia, for example, is the largest producer of oil palm in the Americas, but the effects of oil palm cultivation on native fauna are poorly understood. Here, we compared how richness, abundance and composition of terrestrial mammal species differ between oil palm plantations and riparian forest in the Colombian Llanos region. Further, we determined the relationships and influence of landscape and habitat level variables on those metrics. We found that species richness and composition differed significantly between riparian forest and oil palm, with site level richness inside oil palm plantations 47% lower, on average, than in riparian forest. Within plantations, mammalian species richness was strongly negatively correlated with cattle abundance, and positively correlated with the density of undergrowth vegetation. Forest structure characteristics appeared to have weak and similar effects on determining mammal species richness and composition along riparian forest strips. Composition at the landscape level was significantly influenced by cover type, percentage of remaining forest and the distance to the nearest town, whereas within oil palm sites, understory vegetation, cattle relative abundance, and canopy cover had significant effects on community composition. Species specific abundance responses varied between land cover types, with oil palm having positive effects on mesopredators, insectivores and grazers. Our findings suggest that increasing habitat complexity, avoiding cattle and retaining native riparian forest-regardless of its structure-inside oil palm dominated landscapes would help support higher native mammal richness and abundance at both local and landscape scales. PMID- 29795614 TI - Analysis of the resistance mechanisms in sugarcane during Sporisorium scitamineum infection using RNA-seq and microscopy. AB - Smut caused by biotrophic fungus Sporisorium scitamineum is a major disease of cultivated sugarcane that can cause considerable yield losses. It has been suggested in literature that there are at least two types of resistance mechanisms in sugarcane plants: an external resistance, due to chemical or physical barriers in the sugarcane bud, and an internal resistance governed by the interaction of plant and fungus within the plant tissue. Detailed molecular studies interrogating these two different resistance mechanisms in sugarcane are scarce. Here, we use light microscopy and global expression profiling with RNA seq to investigate these mechanisms in sugarcane cultivar CP74-2005, a cultivar that possibly possesses both internal and external defence mechanisms. A total of 861 differentially expressed genes (DEGs) were identified in a comparison between infected and non-infected buds at 48 hours post-inoculation (hpi), with 457 (53%) genes successfully annotated using BLAST2GO software. This includes genes involved in the phenylpropanoid pathway, cell wall biosynthesis, plant hormone signal transduction and disease resistance genes. Finally, the expression of 13 DEGs with putative roles in S. scitamineum resistance were confirmed by quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the results were consistent with the RNA-seq data. These results highlight that the early sugarcane response to S. scitamineum infection is complex and many of the disease response genes are attenuated in sugarcane cultivar CP74-2005, while others, like genes involved in the phenylpropanoid pathway, are induced. This may point to the role of the different disease resistance mechanisms that operate in cultivars such as CP74-2005, whereby the early response is dominated by external mechanisms and then as the infection progresses, the internal mechanisms are switched on. Identification of genes underlying resistance in sugarcane will increase our knowledge of the sugarcane-S. scitamineum interaction and facilitate the introgression of new resistance genes into commercial sugarcane cultivars. PMID- 29795618 TI - Eye position affects flight altitude in visual approach to landing independent of level of expertise of pilot. AB - The present study addresses the effect of the eye position in the cockpit on the flight altitude during the final approach to landing. Three groups of participants with different levels of expertise (novices, trainees, and certified pilots) were given a laptop with a flight simulator and they were asked to maintain a 3.71 degrees glide slope while landing. Each participant performed 40 approaches to the runway. During 8 of the approaches, the point of view that the flight simulator used to compute the visual scene was slowly raised or lowered with 4 cm with respect to the cockpit, hence moving the projection of the visible part of the cockpit down or up in the visible scene in a hardly noticeable manner. The increases and decreases in the simulated eye height led to increases and decreases in the altitude of the approach trajectories, for all three groups of participants. On the basis of these results, it is argued that the eye position of pilots during visual approaches is a factor that contributes to the risk of black hole accidents. PMID- 29795617 TI - Dietary supplementation with yeast hydrolysate in pregnancy influences colostrum yield and gut microbiota of sows and piglets after birth. AB - Dietary supplementation with yeast derivatives (YD) contributes to the health and physiology of sows and piglets, but few studies have focused on how it influences gut health and performance of sows and piglets. The goal was therefore to examine whether YD, based on brewer's yeast hydrolysate added to pregnancy diet, would affect colostrum composition, yield (CY) and gut microbiota of sows and piglets. Sows were allocated to either a control diet (n = 19) or a control diet supplemented with 2g YD/kg (n = 18) during the pregnancy. Piglets suckling belonging to the control sows (n = 114) and supplemented sows (n = 108) were also included in the study. Gut microbiota populations of sows at farrowing and piglets at one and four weeks of age were assessed using 16S rRNA gene sequencing. Colostrum samples were examined for nutritional composition and immunoglobulin (Ig) content. All piglets were individually weighed at birth and 24 hours later in order to calculate CY, and later at four weeks to calculate average daily gain (ADG). Protein, lactose and dry matter content of colostrum did not significantly differ between the two groups, while sows fed YD had higher levels of fat in their colostrum (P < 0.05). Immunoglobulin A, IgM and IgG levels in colostrum did not differ between the two groups (P >0.05). Colostrum yield was lower in the control than that in YD group (3701g vs. 4581 g; P <0.05). Although the YD supplementation did not change fecal bacteria diversity in sow, more beneficial and fermentative bacteria (Roseburia, Paraprevotella, Eubacterium) were found in the YD fed group (P <0.01) while, some opportunistic pathogens, including Proteobacteria, especially the genera Desulfovibrio, Escherichia/Shigella and Helicobacter, were suppressed. Piglets at one week of age from sows fed YD had more beneficial microbial populations with significant diversity and fewer opportunistic pathogens. Additionally, we established a Pearson's correlations between CY, colostrum components, piglet birth weight and fecal microbiota. Therefore, YD added to the sow diet during pregnancy increases colostrum availability and its energy content for neonate piglets, also promoting beneficial maternal microbial sources for neonate. PMID- 29795616 TI - Health related quality of life in adults after burn injuries: A systematic review. AB - OBJECTIVES: Measurement of health-related quality of life (HRQL) is essential to qualify the subjective burden of burns in survivors. We performed a systematic review of HRQL studies in adult burn patients to evaluate study design, instruments used, methodological quality, and recovery patterns. METHODS: A systematic review was performed. Relevant databases were searched from the earliest record until October 2016. Studies examining HRQL in adults after burn injuries were included. Risk of bias was scored using the Quality in Prognostic Studies tool. RESULTS: Twenty different HRQL instruments were used among the 94 included studies. The Burn Specific Health Scale-Brief (BSHS-B) (46%), the Short Form-36 (SF-36) (42%) and the EuroQol questionnaire (EQ-5D) (9%) were most often applied. Most domains, both mentally and physically orientated, were affected shortly after burns but improved over time. The lowest scores were reported for the domains 'work' and 'heat sensitivity' (BSHS-B), 'bodily pain', 'physical role limitations' (SF-36), and 'pain/discomfort' (EQ-5D) in the short-term and for 'work' and 'heat sensitivity', 'emotional functioning' (SF-36), 'physical functioning' and 'pain/discomfort' in the long-term. Risk of bias was generally low in outcome measurement and high in study attrition. CONCLUSION: Consensus on preferred validated methodologies of HRQL measurement in burn patients would facilitate comparability across studies, resulting in improved insights in recovery patterns and better estimates of HRQL after burns. We recommend to develop a guideline on the measurement of HRQL in burns. Five domains representing a variety of topics had low scores in the long-term and require special attention in the aftermath of burns. PMID- 29795619 TI - Socio-cognitive load and social anxiety in an emotional anti-saccade task. AB - The anti-saccade task has been used to measure attentional control related to general anxiety but less so with social anxiety specifically. Previous research has not been conclusive in suggesting that social anxiety may lead to difficulties in inhibiting faces. It is possible that static face paradigms do not convey a sufficient social threat to elicit an inhibitory response in socially anxious individuals. The aim of the current study was twofold. We investigated the effect of social anxiety on performance in an anti-saccade task with neutral or emotional faces preceded either by a social stressor (Experiment 1), or valenced sentence primes designed to increase the social salience of the task (Experiment 2). Our results indicated that latencies were significantly longer for happy than angry faces. Additionally, and surprisingly, high anxious participants made more erroneous anti-saccades to neutral than angry and happy faces, whilst the low anxious groups exhibited a trend in the opposite direction. Results are consistent with a general approach-avoidance response for positive and threatening social information. However increased socio-cognitive load may alter attentional control with high anxious individuals avoiding emotional faces, but finding it more difficult to inhibit ambiguous faces. The effects of social sentence primes on attention appear to be subtle but suggest that the anti saccade task will only elicit socially relevant responses where the paradigm is more ecologically valid. PMID- 29795620 TI - Impact of LINE-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients. AB - Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 +/- 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 +/- 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE 1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients' outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients' outcomes in univariate analysis. PMID- 29795621 TI - Willingness to pay for a cure of low-risk melanoma patients in Germany. AB - Malignant melanoma is potentially life-threatening but in most cases curable if detected early. Willingness to pay (WTP) is a preference-based construct that reflects burden of disease by assessment of the monetary value for a hypothetical cure from disease. Since WTP (directly as total amount of money) has not been assessed so far in patients with low risk melanoma, it was interesting to gain insights in this patient population and then, in a second step, compare it directly with the WTP of their treating dermato-oncologists. WTP was assessed in 125 patients with low-risk melanoma and additionally in 105 treating physicians, asking for the one-time and continuous payments they would be willing to make for a sustainable cure, both as absolute sums and as percentages of monthly income. The median WTP based on one-time payment was ?10,000 for patients and ?100,000 for physicians; relative numbers were 100% versus 300% of monthly income. For continuous monthly payments, WTP was ?500 for patients and ?1000 for physicians, relative numbers 25% and 50% of income, respectively. Even after controlling for income differences, there was a significantly higher WTP in physicians for all four questions. Compared to patients with chronic skin diseases such as vitiligo, rosacea, atopic eczema and psoriasis, patients with low-risk melanoma showed a significantly higher WTP. Our data suggest that there is a relevant burden of disease even in patients with low-risk tumors. Higher WTP of physicians underlines the prevalence of differences in disease perception. PMID- 29795622 TI - Nonsensical choices? Fall armyworm moths choose seemingly best or worst hosts for their larvae, but neonate larvae make their own choices. AB - Selecting optimal host plants is critical for herbivorous insects, such as fall armyworm (Spodoptera frugiperda), an important maize pest in the Americas and Africa. Fall armyworm larvae are presumed to have limited mobility, hence female moths are presumed to be largely responsible for selecting hosts. We addressed host selection by fall armyworm moths and neonate and older (3rd-instar) larvae, as mediated by resistance and herbivory in maize plants. Thus, we compared discrimination among three maize cultivars with varying degrees of resistance to fall armyworm, and between plants subjected or not to two types of herbivory. The cultivars were: (i) susceptible, and deficient in jasmonic acid (JA) production and green leaf volatiles (GLV) emissions (inbred line B73-lox10); (ii) modestly resistant (B73), and; (iii) highly resistant (Mp708). The herbivory types were: (i) ongoing (= fall armyworm larvae present), and; (ii) future (= fall armyworm eggs present). In choice tests, moths laid more eggs on the highly resistant cultivar, and least on the susceptible cultivar, though on those cultivars larvae performed poorest and best, respectively. In the context of herbivory, moths laid more eggs: (i) on plants subject to versus free of future herbivory, regardless of whether plants were deficient or not in JA and GLV production; (ii) on plants subject versus free of ongoing herbivory, and; (iii) on plants not deficient in compared to deficient in JA and GLV production. Neonate larvae dispersed aerially from host plants (i.e. ballooned), and most larvae colonized the modestly resistant cultivar, and fewest the highly resistant cultivar, suggesting quasi directional, directed aerial descent. Finally, dispersing older larvae did not discriminate among the three maize cultivars, nor between maize plants and (plastic) model maize plants, suggesting random, visually-oriented dispersal. Our results were used to assemble a model of host selection by fall armyworm moths and larvae, including recommendations for future research. PMID- 29795623 TI - "We are doing it together"; The integral role of caregivers in a patients' transition home from the medicine unit. AB - BACKGROUND: An admission to hospital for acute illness can be difficult for patients and lead to high levels of anxiety. Patients are given a lot of information throughout their hospital stay and instructions at discharge to follow when they get home. For complex medical patients, the ability to retain, understand, and adhere to these instructions is a critical marker of a successful transition. This study was undertaken to explore factors impacting the ability of patients to understand and adhere to instructions. METHODS: A qualitative design of interviews with patients and caregivers was used. Participants were adult patients and caregivers with congestive heart failure, chronic obstructive pulmonary disease, or community-acquired pneumonia being discharged home from three academic acute care hospitals in Ontario, Canada. Semi structured interviews were conducted with participants within one week following their discharge from hospital. Interviews were audiotaped and transcribed. Five independent researchers participated in an iterative process of coding, reviewing, and analyzing the interviews using direct content analysis. RESULTS: In total, 27 participants completed qualitative interviews. Analysis revealed the role of the caregiver to be critical in its relation to the ability of patients to understand and adhere to discharge instructions. Within the topic of caregiving, we draw on three areas of insight: The first clarified how caregivers support patients after they are discharged home from the hospital. The second highlighted how caregiver involvement impacts patient understanding and adherence to discharge instructions. The third revealed system factors that influence a caregiver's involvement when receiving discharge instructions. CONCLUSION: Caregivers play an important role in the transition of a complex medical patient by impacting a patient's ability to understand and adhere to their discharge instructions. The themes identified in this paper highlight opportunities for healthcare providers and institutions to effectively involve caregivers during transitions from acute care hospitals to home. PMID- 29795625 TI - Incidence of sexually transmitted infections during pregnancy. AB - Prevalence of sexually transmitted infections (STI) is high among pregnant women in certain settings. We estimated STI incidence and compared STI risk in pregnant and non-pregnant women. Data came from the Methods for Improving Reproductive Health in Africa (MIRA) study conducted in South Africa and Zimbabwe 2003-2006. Women aged 18-50 years with at least one follow-up visit within 6 months of enrollment were included. Follow-up visits included laboratory testing for pregnancy, chlamydia, gonorrhea, trichomoniasis, and HIV, as well as self-report of hormonal contraceptive (HC) use, sexual behaviors and intravaginal practices. All visits were classified according to pregnancy status. Incidence of each STI was calculated using follow-up time. Cox proportional hazards models were fitted using pregnancy as a time-varying exposure and sexual behaviors and intravaginal practices as time-varying covariates. Among 4,549 women, 766 (16.8%) had a positive pregnancy test. Median follow-up time was 18 months [IQR: 12-24]. The overall incidence rate of chlamydia was 6.7 per 100 person years (py) and 9.9/100py during pregnancy; gonorrhea incidence was 2.7/100py and 4.9/100py during pregnancy; trichomoniasis incidence was 7.1/100py overall and 9.2/100py during pregnancy. Overall HIV incidence was 3.9/100py and 3.8/100py during pregnancy. In crude models, pregnancy increased risk for chlamydia (hazard ratio (HR) 1.5, 95%CI: 1.1-1.2), however there was no increased risk of any measured STI in adjusted models. STI Incidence was high during pregnancy however pregnancy did not increase STI risk after adjustment for sexual behaviors. Greater efforts are needed to help pregnant women avoid STIs. PMID- 29795624 TI - A network analysis of the propagation of evidence regarding the effectiveness of fat-controlled diets in the secondary prevention of coronary heart disease (CHD): Selective citation in reviews. AB - OBJECTIVE: To examine how the first randomised controlled trials (RCTs) evaluating the efficacy of cholesterol-lowering diets in the secondary prevention of coronary heart disease were interpreted in reviews of the literature prior to the National Institutes of Health consensus conference in 1984. DESIGN: Claim specific citation network analysis was used to study the network of citations between reviews and RCTs over a defined period (1969-1984). RCTs were identified and classified according to whether their conclusions supported or opposed the use of dietary fat modification/restriction in the secondary prevention of coronary heart disease. Each review published in this period that cited any of the RCTs was classified as supportive, neutral, or unsupportive to the use of dietary fat modification based on a quotation analysis of its evaluation of the findings of these RCTs. Citation bias and underutilisation were detected by applying a comparative density measure, in-degree centrality, and out-degree in a series of sub-graph analyses. RESULTS: In total, 66 unique publications were identified (four RCTs-one supportive, three unsupportive; 62 reviews-28 supportive, 17 neutral, 17 unsupportive). On average, supportive reviews underutilised the available RCTs to a greater degree than other reviews. Amongst the supportive group, citation bias was common-23 (82%) reviews cited only the one RCT that was supportive. CONCLUSION: Most reviews that disseminated a supportive evaluation of the results of RCTs in the context of secondary prevention cited only data that supported this position. PMID- 29795626 TI - Feasibility of Electronic Health Information and Surveillance System (eHISS) for disease symptom monitoring: A case of rural Ghana. AB - INTRODUCTION: The current surge of mobile phone use in many African countries creates the opportunity to provide caregivers with limited access to the health care system with vital health recommendations. At the same time such communication system can be utilised to collect tempero-spatial data on disease symptoms. OBJECTIVE: We assessed the feasibility of an mHealth system among caregivers with children under-five years, designed as a health information and surveillance tool in a rural district of Ghana. METHODS: A mobile phone-based electronic health information and surveillance system was piloted from February to December 2015. Toll-free numbers were provided to 1446 caregivers, which they could call to receive health advice in case their children showed disease symptoms. The system was setup to evaluate the illness of a sick child. Symptoms reported via the system were evaluated and compared to clinician's report after follow-up. Cogency of the reported symptoms was assessed using Cohen's kappa coefficient. RESULTS: A total of 169 children with disease symptoms were identified based on phone calls from caregivers. The predominant reported symptoms were fever (64%; n = 108), cough (55%; n = 93) and diarrhoea (33%; n = 55). Temporal pattern of symptomatic cases revealed a peak saturation in the month of September, with fever registering the highest number of symptoms observed. Reported symptoms and clinician's report revealed a very good agreement for fever (95%, kappa = 0.89); good for diarrhoea (87%, kappa = 0.73) and moderate for cough (76%, kappa = 0.49). CONCLUSION: This pilot concept, has demonstrated the practicality of using mobile phones for assessing childhood disease symptoms and encouraging caregivers to seek early treatment for their children if needed. The strategy to use mobile phones in disease surveillance and treatment support is a promising strategy especially for areas with limited access to the health care system. PMID- 29795627 TI - Inactivation of Salmonella Typhimurium and Listeria monocytogenes on ham with nonthermal atmospheric pressure plasma. AB - The application of cold atmospheric pressure plasma (CAP) for decontamination of sliced ready-to-eat (RTE) meat products (in this case, rolled fillets of ham), inoculated with Salmonella (S.) Typhimurium and Listeria (L.) monocytogenes was investigated. Cold atmospheric plasma (CAP) is an ionised gas that includes highly reactive species and ozone, interacting with cell membranes and DNA of bacteria. The mode of action of CAPs includes penetration and disruption of the outer cell membrane or intracellular destruction of DNA located in the cytoplasm. Inoculated ham was treated for 10 and 20 min with CAP generated by a surface micro-discharge-plasma source using cost-effective ambient air as working gas with different humidity levels of 45-50 and 90%. The chosen plasma modes had a peak-to-peak voltage of 6.4 or 10 kV and a frequency of 2 and 10 kHz. Under the tested conditions, the direct effectiveness of CAP on microbial inactivation was limited. Although all treated samples showed significant reductions in the microbial load subsequent to plasma treatment, the maximum inactivation of S. Typhimurium was 1.14 lg steps after 20 min of CAP-treatment (p<0.05), and L. monocytogenes was reduced by 1.02 lg steps (p<0.05) using high peak-to-peak voltage of 10 kV and a frequency of 2 kHz regardless of moisture content. However, effective inactivation was achieved by a combination of CAP-treatment and cold storage at 8 degrees C +/- 0.5 degrees C for 7 and 14 days after packaging under sealed high nitrogen gas flush (70% N2, 30% CO2). Synergistic effects of CAP and cold storage for 14 days led to a clearer decrease in the microbial load of 1.84 lg steps for S. Typhimurium (p<0.05) and 2.55 lg steps for L. monocytogenes (p<0.05). In the case of L. monocytogenes, subsequent to CAP treatment (10 kV, 2 kHz) and cold storage, microbial counts were predominantly below the detection limit. Measurement showed that after CAP-treatment, surface temperature of ham did not exceed the room temperature of 22 degrees C +/- 2 degrees C. With the application of humidity levels of 45-50%, the colour distance DeltaE increased in CAP treated samples due to a decrease in L* values. In conclusion, effectiveness of CAP-treatment was limited. However, the combination of CAP-treatment and cold storage of samples under modified-atmospheric conditions up to 14 days could significantly reduce microorganisms on RTE ham. Further investigations are required to improve effectiveness of CAP-treatment. PMID- 29795628 TI - Predicting opioid receptor binding affinity of pharmacologically unclassified designer substances using molecular docking. AB - Opioids represent a highly-abused and highly potent class of drugs that have become a significant threat to public safety. Often there are little to no pharmacological and toxicological data available for new, illicitly used and abused opioids, and this has resulted in a growing number of serious adverse events, including death. The large influx of new synthetic opioids permeating the street-drug market, including fentanyl and fentanyl analogs, has generated the need for a fast and effective method to evaluate the risk a substance poses to public safety. In response, the US FDA's Center for Drug Evaluation and Research (CDER) has developed a rapidly-deployable, multi-pronged computational approach to assess a drug's risk to public health. A key component of this approach is a molecular docking model to predict the binding affinity of biologically uncharacterized fentanyl analogs to the mu opioid receptor. The model was validated by correlating the docking scores of structurally diverse opioids with experimentally determined binding affinities. Fentanyl derivatives with sub nanomolar binding affinity at the mu receptor (e.g. carfentanil and lofentanil) have significantly lower binding scores, while less potent fentanyl derivatives have increased binding scores. The strong correlation between the binding scores and the experimental binding affinities suggests that this approach can be used to accurately predict the binding strength of newly identified fentanyl analogs at the mu receptor in the absence of in vitro data and may assist in the temporary scheduling of those substances that pose a risk to public safety. PMID- 29795629 TI - Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis. AB - BACKGROUND: Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs. METHODS: We used data from Phase 3 randomized trials that compared an FDA approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE. RESULTS: Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73 0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84 0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB. CONCLUSIONS: Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non inferior efficacy, but an overall superior safety profile. PMID- 29795631 TI - Data-assisted reduced-order modeling of extreme events in complex dynamical systems. AB - The prediction of extreme events, from avalanches and droughts to tsunamis and epidemics, depends on the formulation and analysis of relevant, complex dynamical systems. Such dynamical systems are characterized by high intrinsic dimensionality with extreme events having the form of rare transitions that are several standard deviations away from the mean. Such systems are not amenable to classical order-reduction methods through projection of the governing equations due to the large intrinsic dimensionality of the underlying attractor as well as the complexity of the transient events. Alternatively, data-driven techniques aim to quantify the dynamics of specific, critical modes by utilizing data-streams and by expanding the dimensionality of the reduced-order model using delayed coordinates. In turn, these methods have major limitations in regions of the phase space with sparse data, which is the case for extreme events. In this work, we develop a novel hybrid framework that complements an imperfect reduced order model, with data-streams that are integrated though a recurrent neural network (RNN) architecture. The reduced order model has the form of projected equations into a low-dimensional subspace that still contains important dynamical information about the system and it is expanded by a long short-term memory (LSTM) regularization. The LSTM-RNN is trained by analyzing the mismatch between the imperfect model and the data-streams, projected to the reduced-order space. The data-driven model assists the imperfect model in regions where data is available, while for locations where data is sparse the imperfect model still provides a baseline for the prediction of the system state. We assess the developed framework on two challenging prototype systems exhibiting extreme events. We show that the blended approach has improved performance compared with methods that use either data streams or the imperfect model alone. Notably the improvement is more significant in regions associated with extreme events, where data is sparse. PMID- 29795630 TI - Sertoli cell-specific ablation of miR-17-92 cluster significantly alters whole testis transcriptome without apparent phenotypic effects. AB - MicroRNAs are frequently organized into polycistronic clusters whose transcription is controlled by a single promoter. The miR-17-92 cluster is expressed in most embryonic and postnatal organs. It is a potent oncogene associated to several types of cancer and it is involved in several important developmental processes. In the testis, expression of the miR-17-92 cluster in the germ cells is necessary to maintain normal spermatogenesis. This cluster is also expressed in Sertoli cells (the somatic cells of the seminiferous tubules), which require miRNAs for correct cell development and survival. To study the possible role of miR-17-92 in Sertoli cell development and function and, in order to overcome the postnatal lethality of miR-17-92-/ mice, we conditionally deleted it in embryonic Sertoli cells shortly after the sex determination stage using an Amh-Cre allele. Mutant mice developed apparently normal testes and were fertile, but their testis transcriptomes contained hundreds of moderately deregulated genes, indicating that testis homeostasis is tightly controlled in mammals and that miR-17-92 expression in Sertoli cells contribute to maintain normal gene expression levels, but is unnecessary for testis development and function. Our results show that significant deregulation of hundreds of genes might have no functional consequences. PMID- 29795632 TI - Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury. AB - AIM: Endotoxin-mediated liver inflammation is a key component of many acute and chronic liver diseases contributing to liver damage, fibrosis and eventually organ failure. Here, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate regarding its anti inflammatory and anti-fibrogenic properties. METHODS: Anti-inflammatory properties of UDCA-LPE were evaluated in a mouse model of D galactosamine/lipopolysaccharide (GalN/LPS)-induced acute liver injury, LPS treated RAW264.7 macrophages and murine primary Kupffer cells. Furthermore, anti inflammatory and anti-fibrotic effects of UDCA-LPE were studied on primary hepatic stellate cells (HSC) incubated with supernatant from LPS+/-UDCA-LPE treated RAW264.7 cells. RESULTS: UDCA-LPE ameliorated LPS-induced increase of IL 6, TNF-alpha, TGF-beta, NOX-2 in the GalN/LPS model by up to 80.2% for IL-6. Similarly, UDCA-LPE markedly decreased the expression of inflammatory cytokines IL-6, TNF-alpha and TGF-beta as well as the chemokines MCP1 and RANTES in LPS stimulated RAW 264.7 cells. Anti-inflammatory effects were also observed in primary murine Kupffer cells. Mechanistic evaluation revealed a reversion of LPS activated pro-inflammatory TLR4 pathway by UDCA-LPE. Moreover, UDCA-LPE inhibited iNOS and NOX-2 expression while activating eNOS via phosphorylation of AKT and pERK1/2 in RAW264.7 cells. HSC treated with conditioned medium from LPS+/-UDCA LPE RAW264.7 cells showed lower fibrogenic activation due to less SMAD2/3 phosphorylation, reduced expression of profibrogenic CTGF and reduced pro inflammatory chemokine expression. CONCLUSION: In the setting of endotoxin mediated liver inflammation, UDCA-LPE exerts profound anti-inflammatory and anti fibrotic effect implying a promising potential for the drug candidate as an experimental approach for the treatment of acute and chronic liver diseases. PMID- 29795633 TI - Impact of immigrants on a multi-agent economical system. AB - We consider a multi-agent model of a simple economical system and study the impacts of a wave of immigrants on the stability of the system. Our model couples a labor market with a goods market. We first create a stable economy with N agents and study the impact of adding n new workers in the system. The time to reach a new equilibrium market is found to obey a power law in n. The new wages and market prices are observed to decrease as 1/n, whereas the wealth of agents remains unchanged. PMID- 29795635 TI - Novel isoguanine derivative of unlocked nucleic acid-Investigations of thermodynamics and biological potential of modified thrombin binding aptamer. AB - Thrombin binding aptamer (TBA), is a short DNA 15-mer that forms G-quadruplex structure and possesses anticoagulant properties. Some chemical modifications, including unlocked nucleic acids (UNA), 2'-deoxy-isoguanosine and 2'-deoxy-4 thiouridine were previously found to enhance the biological activity of TBA. In this paper, we present thermodynamic and biological characteristics of TBA variants that have been modified with novel isoguanine derivative of UNA as well as isoguanosine. Additionally, UNA-4-thiouracil and 4-thiouridine were also introduced simultaneously with isoguanine derivatives. Thermodynamic analysis indicates that the presence of isoguanosine in UNA or RNA series significantly decreases the stability of G-quadruplex structure. The highest destabilization is observed for substitution at one of the G-tetrad position. Addition of 4 thiouridine in UNA or RNA series usually decreases the unfavorable energetic cost of the presence of UNA or RNA isoguanine. Circular dichroism and thermal denaturation spectra in connection with thrombin time assay indicate that the introduction of UNA-isoguanine or isoguanosine into TBA negatively affects G quadruplex folding and TBA anticoagulant properties. These findings demonstrate that the highly-ordered structure of TBA is essential for inhibition of thrombin activity. PMID- 29795634 TI - Defects in nerve conduction velocity and different muscle fibre-type specificity contribute to muscle weakness in Ts1Cje Down syndrome mouse model. AB - BACKGROUND: Down syndrome (DS) is a genetic disorder caused by presence of extra copy of human chromosome 21. It is characterised by several clinical phenotypes. Motor dysfunction due to hypotonia is commonly seen in individuals with DS and its etiology is yet unknown. Ts1Cje, which has a partial trisomy (Mmu16) homologous to Hsa21, is well reported to exhibit various typical neuropathological features seen in individuals with DS. This study investigated the role of skeletal muscles and peripheral nerve defects in contributing to muscle weakness in Ts1Cje mice. RESULTS: Assessment of the motor performance showed that, the forelimb grip strength was significantly (P<0.0001) greater in the WT mice compared to Ts1Cje mice regardless of gender. The average survival time of the WT mice during the hanging wire test was significantly (P<0.0001) greater compared to the Ts1Cje mice. Also, the WT mice performed significantly (P<0.05) better than the Ts1Cje mice in the latency to maintain a coordinated motor movement against the rotating rod. Adult Ts1Cje mice exhibited significantly (P<0.001) lower nerve conduction velocity compared with their aged matched WT mice. Further analysis showed a significantly (P<0.001) higher population of type I fibres in WT compared to Ts1Cje mice. Also, there was significantly (P<0.01) higher population of COX deficient fibres in Ts1Cje mice. Expression of Myf5 was significantly (P<0.05) reduced in triceps of Ts1Cje mice while MyoD expression was significantly (P<0.05) increased in quadriceps of Ts1Cje mice. CONCLUSION: Ts1Cje mice exhibited weaker muscle strength. The lower population of the type I fibres and higher population of COX deficient fibres in Ts1Cje mice may contribute to the muscle weakness seen in this mouse model for DS. PMID- 29795636 TI - ARRIVE has not ARRIVEd: Support for the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines does not improve the reporting quality of papers in animal welfare, analgesia or anesthesia. AB - Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 +/- 11.5% [SD]; nonSUPP: 51.8 +/- 9.0%; p = 0.07, 95% CI of mean difference -0.3-7.3%) and 2015 (SUPP: 60.5 +/- 11.2%; nonSUPP; 60.2 +/- 10.0%; p = 0.89, 95%CI -3.6-4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5-4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research. PMID- 29795638 TI - Asylum-seekers in Germany differ from regularly insured in their morbidity, utilizations and costs of care. AB - In the wake of the European refugee crisis, Germany has received over a million new applications for asylum in the last two years. The health care system is struggling to provide asylum-seekers with access to essential medical services and facilitate their longer-term integration. In this article, we report on the morbidity, utilization and costs of care for a sample of asylum-seekers as compared to a matched group of regularly insured. Using administrative data, we found that asylum-seekers had more hospital and emergency department admissions, including more admissions that could be avoided through good outpatient care or prevention. Their average expenditures were 10 percent higher than for the regularly insured, mostly because of higher hospital expenditures, although there was substantial variation in expenditures by country of origin. Facilitating access to the health care system, especially outpatient and mental health care, could improve asylum-seekers health status and integration, possibly at lower costs. PMID- 29795637 TI - Using the internet for suicide-related purposes: Contrasting findings from young people in the community and self-harm patients admitted to hospital. AB - Despite accelerating interest in the impact of the internet on suicidal behaviour, empirical work has not captured detailed narratives from those who engaged in suicide-related internet use. This study explored the suicide-related online behaviour of two contrasting samples of distressed users, focusing on their purpose, methods and the main content viewed. In-depth interviews were conducted in the UK between 2014-2016 with i) young people in the community; and ii) self-harm patients presenting to hospital emergency departments. Data were analysed using methods of constant comparison. Suicide-related internet use varied according to the severity of suicidal feelings. In the young people sample, where severity was lower, use was characterised by disorganised browsing without clear purpose. A range of content was 'stumbled upon' including information about suicide methods. They also pursued opportunities to interact with others and explore online help. Self-harm patients were a higher severity group with a history of suicidal behaviour. Their use was purposeful and strategic, focused around 'researching' suicide methods to maximise effectiveness. They made specific choices about content viewed; many consulting factual content in preference to user generated accounts, while help content and communication was avoided. Findings indicate further action is necessary to improve online safety. Also, novel online help approaches are needed to engage individuals experiencing suicidal crisis. Awareness of the nature of suicide related internet use and how this may reflect the status of an individual's suicidal thinking could be beneficial to clinicians to promote safety and indicate risk. PMID- 29795639 TI - Propofol elicits autophagy via endoplasmic reticulum stress and calcium exchange in C2C12 myoblast cell line. AB - In this study, we investigated the relationship between propofol and autophagy and examined whether this relationship depends on ER stress, production of ROS (reactive oxygen species), and disruption of calcium (Ca2+) homeostasis. To this end, we measured C2C12 cell apoptosis in vitro, along with Ca2+ levels; ROS production; and expression of proteins and genes associated with autophagy, Ca2+ homeostasis, and ER stress, including LC3 (microtubule-associate protein 1 light chain 3), p62, AMPK (adenosine 5'-monophosphate (AMP)-activated protein kinase), phosphorylated AMPK, mTOR (the mammalian target of rapamycin), phosphorylated mTOR, CHOP (C/BEP homologous protein), and Grp78/Bip (78 kDa glucose-regulated protein). We found that propofol treatment induced autophagy, ER stress, and Ca2+ release. The ratio of phosphorylated AMPK to AMPK increased, whereas the ratio of phosphorylated mTOR to mTOR decreased. Collectively, the data suggested that propofol induced autophagy in vitro through ER stress, resulting in elevated ROS and Ca2+. Additionally, co-administration of an ER stress inhibitor blunted the effect of propofol. PMID- 29795640 TI - Concussion classification via deep learning using whole-brain white matter fiber strains. AB - Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828-0.862 vs. 0.690-0.776, and .632+ error of 0.148-0.176 vs. 0.207-0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury. PMID- 29795642 TI - When the tables are turned: The effects of the 2016 U.S. Presidential election on in-group favoritism and out-group hostility. AB - The outcome of the 2016 U.S. Presidential election was a big surprise to many, as the majority of polls had predicted the opposite outcome. In this two-stage cross sectional study, we focus on how Democrats and Republicans reacted to this electoral surprise and how these reactions might have influenced the way they allocated resources to each other in small groups. We find that, before the election, Republicans showed greater in-group favoritism than Democrats, who treated others equally, regardless of their political affiliation. We then show that Democrats experienced the election outcome as an ego shock and, in the week following the election, reported significantly higher levels of negative emotions and lower levels of self-esteem than Republicans. These reactions then predicted how individuals' decided to allocate resources to others: after the election, Republicans no longer showed in-group favoritism, while Democrats showed out group derogation. We find these decisions when the tables were turned can be partially explained by differences in participants' state self-esteem. PMID- 29795641 TI - Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology. AB - PURPOSE: Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). METHODS: In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. RESULTS: Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non vital grafts, when using a cut off value of 15% for vital tumor cell content. CONCLUSIONS: MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically. PMID- 29795643 TI - Examining the relationship between blood lead level and stunting, wasting and underweight- A cross-sectional study of children under 2 years-of-age in a Bangladeshi slum. AB - Elevated blood lead level (BLL) is known to cause cardiac, immune, and cognitive damage but had not been thoroughly studied in relation to stunting among children under two years of age. We primarily aimed to assess the relationship between elevated BLL, the accumulation of concerned amount of the metal lead in blood and stunting and secondarily-wasting and underweight amongst Bangladeshi children less than two years of age. For this cross-sectional study, BLL measurements, anthropometric data, and socioeconomic indicator information were collected and analyzed for 729 children under two years of age upon enrollment in the MAL-ED study conducted in a Bangladeshi slum area. Univariate, bivariate and multivariate analyses were carried out to observe the proportion and mean and contribution of elevated BLL and other relevant variables in explaining the occurrence of stunting. Of the enrolled subjects, 39.0% were stunted [length-for age z score (LAZ<-2)], 50.3% were male, and 86.6% had an elevated BLL (>=5MUg/dL). Mean BLL of stunted children was 8.47 +/- 3.37 MUg/dL and 8.10 +/- 3.80 MUg/dL for non-stunted children. Proportion of children with elevated BLL was not significantly different between the stunted and non-stunted groups (p>0.05). When adjusted for other variables, elevated BLL was found to be a significant predictor of stunting and underweight (p<0.05) but not wasting (p>0.05). Elevated BLL (p<0.01), child's gender and weight (p<0.001), maternal body mass index (BMI) (p<0.05) and severe household food insecurity (p<0.05) were all significantly associated with stunting in the multivariate model. Increased odds of stunting was also observed for increased BLL. The findings suggest that chronic lead poisoning is significantly associated with high level of stunting among child slum dwellers in Bangladesh. These findings strengthen the argument for improved lead reduction efforts in Bangladesh, where lead poisoning and stunting are both highly prevalent. PMID- 29795644 TI - Discovery and characterization of a thermostable two-domain GH6 endoglucanase from a compost metagenome. AB - Enzymatic depolymerization of recalcitrant polysaccharides plays a key role in accessing the renewable energy stored within lignocellulosic biomass, and natural biodiversities may be explored to discover microbial enzymes that have evolved to conquer this task in various environments. Here, a metagenome from a thermophilic microbial community was mined to yield a novel, thermostable cellulase, named mgCel6A, with activity on an industrial cellulosic substrate (sulfite-pulped Norway spruce) and a glucomannanase side activity. The enzyme consists of a glycoside hydrolase family 6 catalytic domain (GH6) and a family 2 carbohydrate binding module (CBM2) that are connected by a linker rich in prolines and threonines. MgCel6A exhibited maximum activity at 85 degrees C and pH 5.0 on carboxymethyl cellulose (CMC), but in prolonged incubations with the industrial substrate, the highest yields were obtained at 60 degrees C, pH 6.0. Differential scanning calorimetry (DSC) indicated a Tm(app) of 76 degrees C. Both functional data and the crystal structure, solved at 1.88 A resolution, indicate that mgCel6A is an endoglucanase. Comparative studies with a truncated variant of the enzyme showed that the CBM increases substrate binding, while not affecting thermal stability. Importantly, at higher substrate concentrations the full length enzyme was outperformed by the catalytic domain alone, underpinning previous suggestions that CBMs may be less useful in high-consistency bioprocessing. PMID- 29795645 TI - Prevention and treatment of bleomycin-induced pulmonary fibrosis with the lactate dehydrogenase inhibitor gossypol. AB - Pulmonary fibrosis is a chronic and irreversible scarring disease in the lung with poor prognosis. Few therapies are available; therefore it is critical to identify new therapeutic targets. Our lab has previously identified the enzyme lactate dehydrogenase-A (LDHA) as a potential therapeutic target in pulmonary fibrosis. We found increases in LDHA protein and its metabolic product, lactate, in patients with idiopathic pulmonary fibrosis (IPF). Importantly, we described lactate as a novel pro-fibrotic mediator by acidifying the extracellular space, and activating latent transforming growth factor beta (TGF-beta1) in a pH dependent manner. We propose a pro-fibrotic feed-forward loop by which LDHA produces lactate, lactate decreases pH in the extracellular space and activates TGF-beta1 which can further perpetuate fibrotic signaling. Our previous work also demonstrates that the LDHA inhibitor gossypol inhibits TGF-beta1-induced myofibroblast differentiation and collagen production in vitro. Here, we employed a mouse model of bleomycin-induced pulmonary fibrosis to test whether gossypol inhibits pulmonary fibrosis in vivo. We found that gossypol dose-dependently inhibits bleomycin-induced collagen accumulation and TGF-beta1 activation in mouse lungs when treatment is started on the same day as bleomycin administration. Importantly, gossypol was also effective at treating collagen accumulation when delayed 7 days following bleomycin. Our results demonstrate that inhibition of LDHA with the inhibitor gossypol is effective at both preventing and treating bleomycin-induced pulmonary fibrosis, and suggests that LDHA may be a potential therapeutic target for pulmonary fibrosis. PMID- 29795646 TI - Peak oxygen uptake (VO2peak) across childhood, adolescence and young adulthood in Barth syndrome: Data from cross-sectional and longitudinal studies. AB - : Barth syndrome (BTHS) is an ultra-rare, X-linked recessive disorder characterized by cardio-skeletal myopathy, exercise intolerance, and growth delay. Oxygen uptake during peak exercise (VO2peak) has been shown to be severely limited in individuals with BTHS however; the trajectory of VO2peak from childhood to young adulthood is unknown. The objective of this study was to describe VO2peak from childhood through young adulthood in BTHS. METHODS AND MATERIALS: VO2peak over time was presented through cross-sectional (n = 33 participants) and a longitudinal analyses (n = 12 participants). Retrospective data were obtained through maximal exercise testing on a cycle ergometer from individuals with BTHS who were or are currently enrolled in a research study during July 2006-September 2017. Participants included in the cross-sectional analysis were divided into 3 groups for analysis: 1) children (n = 13), 2) adolescents (n = 8), and 3) young adults (n = 12). Participants in the longitudinal analysis had at least two exercise tests over a span of 2-9 years. RESULTS: VO2peak relative to body weight (ml/kgBW/min), fat-free mass (FFM) and by percent of predicted VO2peak obtained were not significantly different between children, adolescents and young adults. VO2peak did not longitudinally change over a mean time of ~5 years in late adolescent and young adult participants with repeated tests. A model including both cardiac and skeletal muscle variables best predicted VO2peak. CONCLUSIONS: In conclusion, VO2peak relative to body weight and fat-free mass demonstrates short- and long-term stability from childhood to young adulthood in BTHS with some variability among individuals. PMID- 29795648 TI - The impact of eliminating primary school tuition fees on child marriage in sub Saharan Africa: A quasi-experimental evaluation of policy changes in 8 countries. AB - BACKGROUND: Child marriage harms girls' health and hinders progress toward development goals. Randomized studies have shown that providing financial incentives for girls' education can effectively delay marriage, but larger-scale interventions are needed in light of slow progress toward curbing the practice. Many sub-Saharan African countries eliminated primary school tuition fees over the past two decades, resulting in massive increases in enrolment. We measured the effect of these policies on the probability of primary school completion and of marriage before 15 and 18 years of age. METHODS: We used Demographic and Health Surveys to assemble a dataset of women born between 1970 and 2000 in 16 countries. These data were merged with longitudinal information on the timing of tuition fee elimination in each country. We estimated the impact of fee removal using fixed effects regression to compare changes in the prevalence of child marriage over time between women who were exposed to tuition-free primary schooling and those who were not. RESULTS: The removal of tuition fees led to modest average declines in the prevalence of child marriage across all of the treated countries. However, there was substantial heterogeneity between countries. The prevalence of child marriage declined by 10-15 percentage points in Ethiopia and Rwanda following tuition elimination but we found no evidence that the removal of tuition fees had an impact on child marriage rates in Cameroon or Malawi. Reductions in child marriage were not consistently accompanied by increases in the probability of primary school completion. CONCLUSIONS: Eliminating tuition fees led to reductions in child marriage on a national scale in most countries despite challenges with implementation. Improving the quality of the education available may strengthen these effects and bolster progress toward numerous other public health goals. PMID- 29795647 TI - Estimating the cost-effectiveness of a sequential pneumococcal vaccination program for adults in Germany. AB - INTRODUCTION: In Germany, a 23-valent polysaccharide pneumococcal vaccine (PPSV23) is recommended for elderly (60+) and patients 16+ with chronic diseases not associated with immune suppression. For all other patients at risk, sequential immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) first, followed by PPSV23 is recommended. Repeated vaccination with PPSV23 is recommended every 6 years after individual assessment by the physician. This was adopted into the vaccination directive with binding reimbursement and funding. However, additional voluntary services allow statutory health insurances to differentiate from each other. Aim of this study is to estimate the cost effectiveness of voluntary service scenarios compared to the strategy in place to support informed decision making. METHODS: A microsimulation framework with Markov-type process of a population susceptible to pneumococcal disease over a lifetime horizon was developed to compare effectiveness and cost-effectiveness of different vaccination strategies. We simulated 1,000 iterations for seven scenarios. Assumptions were derived from published literature and probabilistic sensitivity analysis was run to show the robustness of the model. RESULTS: Our study indicates that all voluntary service strategies could prevent further clinical cases compared to the existing policy. Depending on the scenario, 48-142 invasive pneumococcal disease (IPD), 24,000-45,000 hospitalized all-cause nonbacteremic pneumonia (NBP), 15,000-45,000 outpatient NBP cases, and 4,000 8,000 deaths could be avoided on average. This refers to potential savings of ?115 Mio. - ?187 Mio. for medical and non-medical costs. Additional costs per patient for the payer are ?2.48 to ?7.13 and for the society ?2.20 to ?6.85. The ICER per LYG ranged from ?3,662 to ?23,061 (payer) and ?3,258 to ?29,617 (societal). All but one scenario was cost-effective in >=60% of the generated 1,000 simulations. CONCLUSION: Compared to the vaccination strategy in place, the different hypothetical scenarios can be considered cost-effective and suitable as additional voluntary services. PMID- 29795649 TI - Longitudinal impacts of pubertal timing and weight status on adolescent Internet use: Analysis from a cohort study of Taiwanese youths. AB - AIM: To investigate the longitudinal impacts of pubertal timing and weight status on Internet use in adolescents. METHODS: Three waves of data on a longitudinal cohort of 7th grade students (N = 2430) were retrieved from the Taiwan Youth Project. Univariate and multivariate regression models were applied using crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) to examine the concomitant impacts of pubertal timing and weight status on adolescent Internet use. RESULTS: The dataset identified 210 (8.7%) students using the Internet for more than 20 hours/week, and 81 (3.3%) were viewing pornographic material online. Early maturing and thin-weight adolescents were at 35% and 46% increased risks of spending long hours on Internet use, respectively. While early puberty was associated with online pornography viewing among males (adjusted OR 1.84, 95% CI 1.04-3.28), early puberty was contrarily a protective factor against online gaming in females (adjusted OR 0.59, 95% CI 0.36-0.96). CONCLUSION: Early puberty was found to be positively related to adolescent Internet use. Appropriate health education and guidance regarding Internet use should be provided to those with different developing needs. PMID- 29795650 TI - Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: Comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion. AB - The potential use of bone progenitors, multipotential stromal cells (MSCs) helping spine fusion is increasing, but convenient MSC sources and effective processing methods are critical factors yet to be optimised. The aim of this study was to test the effect of bone marrow processing on the MSC abundance and to compare the differentiation capabilities of vertebral body-bone marrow (VB-BM) MSCs versus iliac crest-bone marrow (IC-BM) MSCs. We assessed the effect of the red blood cell lysis (ammonium chloride, AC) and density-gradient centrifugation (LymphoprepTM, LMP), on the extracted VB-BM and IC-BM MSC numbers. The MSC abundance (indicated by colony counts and CD45lowCD271high cell numbers), phenotype, proliferation and tri-lineage differentiation of VB-BM MSCs were compared with donor-matched IC-BM MSCs. Importantly, the MSC attachment and osteogenesis were examined when VB-BM and IC-BM samples were loaded on a beta tricalcium phosphate scaffold. In contrast to LMP, using AC yielded more colonies from IC-BM and VB-BM aspirates (p = 0.0019 & p = 0.0201 respectively). For IC-BM and VB-BM, the colony counts and CD45lowCD271high cell numbers were comparable (p = 0.5186, p = 0.2640 respectively). Furthermore, cultured VB-BM MSCs exhibited the same phenotype, proliferative and adipogenic potential, but a higher osteogenic and chondrogenic capabilities than IC-BM MSCs (p = 0.0010 and p = 0.0005 for calcium and glycosaminoglycan (GAG) levels, respectively). The gene expression data confirmed higher chondrogenesis for VB-BM MSCs than IC-BM MSCs, but osteogenic gene expression levels were comparable. When loaded on VitossTM, both MSCs showed a similar degree of attachment and survival, but a better osteogenic ability was detected for VB-BM MSCs as measured by alkaline phosphatase activity (p = 0.0386). Collectively, the BM processing using AC had more MSC yield than using LMP. VB-BM MSCs have a comparable phenotype and proliferative capacity, but higher chondrogenesis and osteogenesis with or without using scaffold than donor-matched IC-BM MSCs. Given better accessibility, VB-BM could be an ideal MSC source for spinal bone fusion. PMID- 29795652 TI - Bone density of the femoral neck in patients on maintenance dialysis. AB - BACKGROUND: Our institution recently started using the femoral neck (FN), as well as the non-shunted distal radius (Rd), to measure bone mineral density (BMD) in patients with chronic kidney disease. We examined the utility and characteristics of this measurement in patients on maintenance dialysis. METHODS: We selected 293 patients on chronic dialysis. We measured Rd and FN BMD using dual-energy X-ray absorptiometry, and we reviewed blood test findings, which included hemoglobin, albumin, blood urea nitrogen, creatinine, adjusted calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone. We conducted a multiple linear regression analysis that was stratified according to sex, age, body weight, height, and dialysis vintage. The Rd and FN BMD values were the dependent variables, and the blood test findings were the independent variables. We compared the areas under the curve (AUCs) of Rd and FN BMD using receiver operating characteristic curve analysis to differentiate between patients with and without fractures. RESULTS: FN BMD was significantly lower than Rd BMD. The general risk factors for osteoporosis, such as low body weight, older age, muscle mass loss, and malnutrition, influenced FN BMD. FN and Rd BMD were not correlated with calcium, phosphorous, or intact parathyroid hormone, whereas a significant, negative correlation with alkaline phosphatase was detected. Both men and women with a history of fragility fractures had significantly lower Rd and FN BMDs than patients without such a history. However, there was no significant difference between the AUCs of FN and Rd BMD for fractures in both men and women. CONCLUSIONS: FN BMD was significantly lower than Rd BMD. Additionally, FN BMD was not inferior to Rd BMD for assessing the risk of fracture in patients on maintenance dialysis. PMID- 29795653 TI - The characteristics of pediatric emergency department visits in Korea: An observational study analyzing Korea Health Panel data. AB - OBJECTIVE: We investigated the characteristics of pediatric emergency department (ED) patients in Korea and determined factors associated with hospital admission after ED treatment. METHODS: Korea Health Panel data from 2008 through 2013 were analyzed retrospectively; we included patients under 18 years old who visited the ED at least once. We collected patient and household epidemiologic data such as sex, age group, region of residence, disability, chronic disease, household income quintile, national health insurance type, use of private insurance, and annual frequency of ED visits. We also examined data related to each ED visit, such as reason for visit, medical service provided, and hospital size/ownership. We then investigated which factors were correlated with case disposition (discharge home or hospital admission) after ED treatment. RESULTS: In total, 3,160 pediatric ED visits occurred during the six-year period. Males (57.5%) and children aged 0-5 years (47.7%) made more visits than females and older children, respectively. The proportion of ED visits for disease (67.7%) was much higher than for injury or poisoning (32.2%), and 452 cases (14.3%) required hospital admission. For hospital admission, the odds ratio (OR) of females was 0.73 compared to males, and the OR of children aged 6-11 was 0.68 compared to children aged 0-5. The OR of capital residents was 0.69 compared to province residents, and the OR of the highest income quintile was 0.51 compared to the lowest quintile. The OR of children with private insurance coverage was 0.49 compared to those lacking private insurance, and the OR of ED visits due to disease was 1.82 compared to visits due to injury/poisoning. CONCLUSION: This analysis of clinical and demographic characteristics of pediatric ED visits and hospital admissions can serve as the foundation of future prospective studies required for establishing appropriate policies for the Korean pediatric emergency medical system. PMID- 29795651 TI - Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy. AB - Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy. PMID- 29795654 TI - The characteristic patterns of neuronal avalanches in mice under anesthesia and at rest: An investigation using constrained artificial neural networks. AB - Local perturbations within complex dynamical systems can trigger cascade-like events that spread across significant portions of the system. Cascades of this type have been observed across a broad range of scales in the brain. Studies of these cascades, known as neuronal avalanches, usually report the statistics of large numbers of avalanches, without probing the characteristic patterns produced by the avalanches themselves. This is partly due to limitations in the extent or spatiotemporal resolution of commonly used neuroimaging techniques. In this study, we overcome these limitations by using optical voltage (genetically encoded voltage indicators) imaging. This allows us to record cortical activity in vivo across an entire cortical hemisphere, at both high spatial (~30um) and temporal (~20ms) resolution in mice that are either in an anesthetized or awake state. We then use artificial neural networks to identify the characteristic patterns created by neuronal avalanches in our data. The avalanches in the anesthetized cortex are most accurately classified by an artificial neural network architecture that simultaneously connects spatial and temporal information. This is in contrast with the awake cortex, in which avalanches are most accurately classified by an architecture that treats spatial and temporal information separately, due to the increased levels of spatiotemporal complexity. This is in keeping with reports of higher levels of spatiotemporal complexity in the awake brain coinciding with features of a dynamical system operating close to criticality. PMID- 29795655 TI - A computational framework for predicting obesity risk based on optimizing and integrating genetic risk score and gene expression profiles. AB - Recent large-scale genome-wide association studies have identified tens of genetic loci robustly associated with Body Mass Index (BMI). Gene expression profiles were also found to be associated with BMI. However, accurate prediction of obesity risk utilizing genetic data remains challenging. In a cohort of 75 individuals, we integrated 27 BMI-associated SNPs and obesity-associated gene expression profiles. Genetic risk score was computed by adding BMI-increasing alleles. The genetic risk score was significantly correlated with BMI when an optimization algorithm was used that excluded some SNPs. Linear regression and support vector machine models were built to predict obesity risk using gene expression profiles and the genetic risk score. An adjusted R2 of 0.556 and accuracy of 76% was achieved for the linear regression and support vector machine models, respectively. In this paper, we report a new mathematical method to predict obesity genetic risk. We constructed obesity prediction models based on genetic information for a small cohort. Our computational framework serves as an example for using genetic information to predict obesity risk for specific cohorts. PMID- 29795657 TI - No-U-turn sampling for fast Bayesian inference in ADMB and TMB: Introducing the adnuts and tmbstan R packages. AB - Statistical inference is a widely-used, powerful tool for learning about natural processes in diverse fields. The statistical software platforms AD Model Builder (ADMB) and Template Model Builder (TMB) are particularly popular in the ecological literature, where they are typically used to perform frequentist inference of complex models. However, both lack capabilities for flexible and efficient Markov chain Monte Carlo (MCMC) integration. Recently, the no-U-turn sampler (NUTS) MCMC algorithm has gained popularity for Bayesian inference through the software Stan because it is efficient for high dimensional, complex hierarchical models. Here, we introduce the R packages adnuts and tmbstan, which provide NUTS sampling in parallel and interactive diagnostics with ShinyStan. The ADMB source code was modified to provide NUTS, while TMB models are linked directly into Stan. We describe the packages, provide case studies demonstrating their use, and contrast performance against Stan. For TMB models, we show how to test the accuracy of the Laplace approximation using NUTS. For complex models, the performance of ADMB and TMB was typically within +/- 50% the speed of Stan. In one TMB case study we found inaccuracies in the Laplace approximation, potentially leading to biased inference. adnuts provides a new method for estimating hierarchical ADMB models which previously were infeasible. TMB users can fit the same model in both frequentist and Bayesian paradigms, including using NUTS to test the validity of the Laplace approximation of the marginal likelihood for arbitrary subsets of parameters. These software developments extend the available statistical methods of the ADMB and TMB user base with no additional effort by the user. PMID- 29795656 TI - Drought-tolerant and drought-sensitive genotypes of maize (Zea mays L.) differ in contents of endogenous brassinosteroids and their drought-induced changes. AB - The contents of endogenous brassinosteroids (BRs) together with various aspects of plant morphology, water management, photosynthesis and protection against cell damage were assessed in two maize genotypes that differed in their drought sensitivity. The presence of 28-norbrassinolide in rather high quantities (1-2 pg mg-1 fresh mass) in the leaves of monocot plants is reported for the first time. The intraspecific variability in the presence/content of the individual BRs in drought-stressed plants is also described for the first time. The drought resistant genotype was characterised by a significantly higher content of total endogenous BRs (particularly typhasterol and 28-norbrassinolide) compared with the drought-sensitive genotype. On the other hand, the drought-sensitive genotype showed higher levels of 28-norcastasterone. Both genotypes also differed in the drought-induced reduction/elevation of the levels of 28-norbrassinolide, 28 norcastasterone, 28-homocastasterone and 28-homodolichosterone. The differences observed between both genotypes in the endogenous BR content are probably correlated with their different degrees of drought sensitivity, which was demonstrated at various levels of plant morphology, physiology and biochemistry. PMID- 29795658 TI - A stable isotope dilution tandem mass spectrometry method of major kavalactones and its applications. AB - Kava is regaining its popularity with detailed characterizations warranted. We developed an ultraperformance liquid chromatography high-resolution tandem mass spectrometry (UPLC-MS/MS) method for major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin and desmethoxyyangonin) with excellent selectivity and specificity. The method has been validated for different matrices following the Food and Drug Administration guidance of analytical procedures and methods validation. The scope of this method has been demonstrated by quantifying these kavalactones in two kava products, characterizing their tissue distribution and pharmacokinetics in mice, and detecting their presence in human urines and plasmas upon kava intake. As expected, the abundances of these kavalactones differed significantly in kava products. All of them exhibited a large volume of distribution with extensive tissue affinity and adequate mean residence time (MRT) in mice. This method also successfully quantified these kavalactones in human body fluids upon kava consumption at the recommended human dose. This UPLC MS/MS method therefore can be used to characterize kava products and its pharmacokinetics in animals and in humans. PMID- 29795659 TI - Variation in photosynthesis and stomatal conductance among red maple (Acer rubrum) urban planted cultivars and wildtype trees in the southeastern United States. AB - Photosynthesis is a fundamental process that trees perform over fluctuating environmental conditions. This study of red maple (Acer rubrum L.) characterizes photosynthesis, stomatal conductance, and water use efficiency in planted cultivars relative to wildtype trees. Red maple is common in cities, yet there is little understanding of how physiological processes affect the long-term growth, condition, and ecosystem services provided by urban trees. In the first year of our study, we measured leaf-level gas exchange and performed short-term temperature curves on urban planted cultivars and on suburban and rural wildtype trees. In the second year, we compared urban planted cultivars and urban wildtype trees. In the first year, urban planted trees had higher maximum rates of photosynthesis and higher overall rates of photosynthesis and stomatal conductance throughout the summer, relative to suburban or rural wildtype trees. Urban planted trees again had higher maximum rates of photosynthesis in the second year. However, urban wildtype trees had higher water use efficiency as air temperatures increased and similar overall rates of photosynthesis, relative to cultivars, in mid and late summer. Our results show that physiological differences between cultivars and wildtype trees may relate to differences in their genetic background and their responses to local environmental conditions, contingent on the identity of the horticultural variety. Overall, our results suggest that wildtype trees should be considered for some urban locations, and our study is valuable in demonstrating how site type and tree type can inform tree planting strategies and improve long-term urban forest sustainability. PMID- 29795660 TI - Influence of three artificial light sources on oviposition and half-life of the Black Soldier Fly, Hermetia illucens (Diptera: Stratiomyidae): Improving small scale indoor rearing. AB - Hermetia illucens (L.), the Black Soldier Fly, has received increased scientific attention for its potential in circular waste management where larvae can serve as feedstuff for livestock and for biodiesel production. The flies occur naturally in (sub)-tropical and warm-temperate climates, and their mating depends on space and sunlight. Small-scale indoor rearing of Black Soldier Flies has been challenging because they react sensitive to artificial light sources and cage sizes, but recent studies have shown that small-scale rearing under artificial light is feasible. Here, we test the influence of three artificial light sources (light-emitting diodes, fluorescent lamps, and halogen lamps) on small-scale indoor rearing. Three experiments were conducted to compare oviposition traits (pre-oviposition period, total oviposition-period, and egg mass per female) and half-life among the three light sources. Oviposition did not differ among the three light sources, but male and female half-life did. Based on the performance of the light-emitting diodes and their outstanding energy efficiency, we recommend this light source for small-scale indoor rearing of Black Soldier Flies. PMID- 29795661 TI - Unusual and unique distribution of anal high-risk human papillomavirus (HR-HPV) among men who have sex with men living in the Central African Republic. AB - BACKGROUND: High-risk (HR) human papillomavirus (HPV) infection remains a great concern in relation to African men who have sex with men (MSM), especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic. METHODS: MSM receiving care at the Centre National de Reference des Infections Sexuellement Transmissibles et de la Therapie Antiretrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using AnyplexTM II HPV28 test (Seegene, South Korea), and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes. RESULTS: 42 MSM (mean age, 23.2 years; range, 14-39) including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4%) with 2.7 genotypes per anal samples than in HIV-negative (7.7%) with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9(r) vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9%) contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02). CONCLUSION: MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as predominant HPV suggests possible geographic specificities in the molecular epidemiology of HR-HPV in sub-Saharan Africa. Scaling up prevention strategies against HPV infection and related cancers adapted for MSM in Africa should be prioritized. Innovative interventions should be conceived for the MSM population living in Bangui. PMID- 29795662 TI - Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet. AB - Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient. PMID- 29795663 TI - Clinical, pathological, and molecular features of classical and L-type atypical BSE in goats. AB - Monitoring of small ruminants for transmissible spongiform encephalopathies (TSEs) has recently become more relevant after two natural scrapie suspected cases of goats were found to be positive for classical BSE (C-BSE). C-BSE probably established itself in this species unrecognized, undermining disease control measures. This opens the possibility that TSEs in goats may remain an animal source for human prion diseases. Currently, there are no data regarding the natural presence of the atypical BSE in caprines. Here we report that C-BSE and L-type atypical BSE (L-BSE) isolates from bovine species are intracerebrally transmissible to goats, with a 100% attack rate and a significantly shorter incubation period and survival time after C-BSE than after L-BSE experimental infection, suggesting a lower species barrier for classical agentin goat. All animals showed nearly the same clinical features of disease characterized by skin lesions, including broken hair and alopecia, and abnormal mental status. Histology and immunohistochemistry showed several differences between C-BSE and L BSE infection, allowing discrimination between the two different strains. The lymphoreticular involvement we observed in the C-BSE positive goats argues in favour of a peripheral distribution of PrPSc similar to classical scrapie. Western blot and other currently approved screening tests detected both strains in the goats and were able to classify negative control animals. These data demonstrate that active surveillance of small ruminants, as applied to fallen stock and/or healthy slaughter populations in European countries, is able to correctly identify and classify classical and L-BSE and ultimately protect public health. PMID- 29795666 TI - Correction: Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts. AB - [This corrects the article DOI: 10.1371/journal.pone.0191137.]. PMID- 29795665 TI - Accurate pain reporting training diminishes the placebo response: Results from a randomised, double-blind, crossover trial. AB - Analgesic trials frequently fail to demonstrate efficacy of drugs known to be efficacious. Poor pain reporting accuracy is a possible source for this low essay sensitivity. We report the effects of Accurate-Pain-Reporting-Training (APRT) on the placebo response in a trial of Pregabalin for painful-diabetic-neuropathy. The study was a two-stage randomized, double-blind trial: In Stage-1 (Training) subjects were randomized to APRT or No-Training. The APRT participants received feedback on the accuracy of their pain reports in response to mechanical stimuli, measured by R-square score. In Stage-2 (Evaluation) all subjects entered a placebo-controlled, cross-over trial. Primary (24-h average pain intensity) and secondary (current, 24-h worst, and 24-h walking pain intensity) outcome measures were reported. Fifty-one participants completed the study. APRT patients (n = 28) demonstrated significant (p = 0.036) increases in R-square scores. The APRT group demonstrated significantly (p = 0.018) lower placebo response (0.29 +/- 1.21 vs. 1.48 +/- 2.21, mean difference +/- SD = -1.19+/-1.73). No relationships were found between the R-square scores and changes in pain intensity in the treatment arm. In summary, our training successfully increased pain reporting accuracy and resulted in a diminished placebo response. Theoretical and practical implications are discussed. PMID- 29795664 TI - Attention and working memory deficits in a perinatal nicotine exposure mouse model. AB - BACKGROUND: Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure. METHODOLOGY/PRINCIPAL FINDINGS: Female C57Bl/6 mice received drinking water containing nicotine (100MUg/ml) + saccharin (2%) starting 3 weeks prior to breeding and continuing throughout pregnancy, and until 3 weeks postpartum. Over the same period, female mice in two control groups received drinking water containing saccharin (2%) or plain drinking water. Offspring from each group were weaned at 3-weeks of age and subjected to behavioral analyses at 3 months of age. We examined spontaneous locomotor activity, anxiety-like behavior, spatial working memory, object based attention, recognition memory and impulsive-like behavior. We found significant deficits in attention and working memory only in male mice, and no significant changes in the other behavioral phenotypes in male or female mice. Exposure to saccharin alone did not produce significant changes in either sex. CONCLUSION/SIGNIFICANCE: The perinatal nicotine exposure produced significant deficits in attention and working memory in a sex-dependent manner in that the male but not female offspring displayed these behaviors. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and have been reported in other studies that used pre- or perinatal nicotine exposure. Therefore, we suggest that preclinical models of developmental nicotine exposure could be useful tools for modeling ADHD and related disorders. PMID- 29795667 TI - Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue plasminogen activator. AB - Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections. PMID- 29795668 TI - Correction: Utilization of Landsat-8 data for the estimation of carrot and maize crop water footprint under the arid climate of Saudi Arabia. AB - [This corrects the article DOI: 10.1371/journal.pone.0192830.]. PMID- 29795669 TI - Proximal fibular osteotomy to treat medial compartment knee osteoarthritis: Preoperational factors for short-term prognosis. AB - OBJECTIVE: The purpose of this study was to determine the association between preoperational factors and patients' short-term outcome after proximal fibular osteotomy (PFO) and to provide a basis for detailed surgical indication and patient selection. METHODS: This was a retrospective study of patients undergoing PFO between January 2015 and December 2015. Preoperational clinical data including gender, age, duration of disease, visual analogue score (VAS) and American Knee Society (KSS) score were collected. The radiological factors including hip-knee-ankle angle (HKA angle), condyle-plateau angle (CP angle), Kellgren and Lawrence grade (KL grade), joint space width of both compartments and settlement value were also considered. Patients were followed for at 12 months postoperatively. Both clinical and functional KSS scores were obtained. The outcome of interest was divided into clinical outcome and functional outcome. For each, two criteria were defined: satisfaction and significant improvement. Satisfaction is characterized by a KSS clinical or functional score over 70 points (excellent and good results); significant improvement refers to an increase in KSS scores of more than 15 points. Bivariate logistic regression for the association between preoperational factors and outcomes of interest was performed. Multivariable logistic regression analyses were used to detect the independent factors affecting the outcomes. RESULTS: A total of 84 patients and 111 knees were followed-up. Of these, 17 knees were from males and 94 were from females. The average age was 59.45+/-8.82 years. The average preoperational VAS score, KSS clinical and functional score were 7.08+/-1.41 points, 49.14+/-10.95 points and 44.97+/-17.71 points, respectively. According to KL grading, there were 17 knees of grade 2, 47 knees of grade 3, and 47 knees of grade 4. In clinical outcomes, there were 51 knees in the satisfaction group and 77 knees in the significant improvement group. In functional outcomes, 43 knees were in the satisfaction group and 76 knees in the significant improvement group. KSS clinical score (OR = 1.134, 95%CI = 1.067-1.205, P = 0.000) was the independent factor associated with clinical satisfaction. Age (OR = 1.072, 95%CI = 1.000 1.150, P = 0.048), VAS score (OR = 1.679, 95%CI = 1.041-2.706, P = 0.033), KSS clinical (OR = 1.072, 95%CI = 1.005-1.144, P = 0.034) and functional (OR = 1.100, 95%CI = 1.044-1.159, P = 0.000) score, HKA angle (OR = 1.345, 95%CI = 1.119 1.617, P = 0.002) and settlement value (OR = 7.540, 95%CI = 1.307-43.484, P = 0.024) were the independent factors associated with functional satisfaction. KSS clinical (OR = 0.905, 95%CI = 0.850-0.963, P = 0.002) score, CP angle (OR = 0.760, 95%CI = 0.593-0.973, P = 0.030) and medial joint space width (OR = 0.001, 95%CI = 0.000-0.107, P = 0.003) were the independent factors associated with significant clinical improvement; VAS score (OR = 1.582, 95%CI = 1.042-2.402, P = 0.031), KSS functional (OR = 0.888, 95%CI = 0.838-0.942, P = 0.000) score, HKA angle (OR = 1.292, 95%CI = 1.101-1.518, P = 0.002) and settlement value (OR = 9.990, 95%CI = 1.485-67.197, P = 0.018) were the independent factors associated with significant functional improvement. CONCLUSIONS: The independent factors affecting postoperative clinical outcome after PFO were KSS clinical score, CP angle and medial joint space width. In addition, the independent factors that influenced functional outcome included age, VAS score, KSS score, HKA angle and settlement value. As objective radiological evidence, HKA angle and settlement value could be used as an important basis for patient selection for PFO. PMID- 29795670 TI - Decreased DNA methylation of a CpG site in the HBAP1 gene in plasma DNA from pregnant women. AB - OBJECTIVE: The objective of this study is to identify potential CpG site(s) or DNA methylation pattern(s) in the pseudo alpha-globin 1 gene (HBAP1 gene), the gene which locates in alpha-thalassemia-1 deletion mutation, to differentiate plasma DNA between pregnant and non-pregnant women. METHOD: DNA methylation profiles of placenta and peripheral blood from the MethBase database were compared to screen differentially methylated regions. This region was confirmed the differential by methylation-sensitive high resolution melt (MS-HRM) analysis. The differential region was used to compare DNA methylation profile of plasma DNA between pregnant and non-pregnant women by bisulfite amplicon sequencing in three levels: overall, individual CpG sites and individual molecules (DNA methylation patterns). RESULT: Using MethBase data, four consecutive CpG sites in the HBAP1 gene were identified as regions of differential DNA methylation between placenta and peripheral blood. The confirmation by MS-HRM showed the differential DNA methylation profile between the placenta and plasma from non-pregnant women. The comparison of DNA methylation profiles between the plasma of pregnant and non pregnant women showed that, in the overall levels of the four CpG sites, DNA methylation of pregnant women was detected at lower levels than non-pregnant women. In the individual CpG site level, only the second CpG site showed differential DNA methylation between the groups. In the DNA methylation pattern level, there was no strongly significant differences in DNA methylation patterns between the pregnant and non-pregnant groups. CONCLUSION: Our result demonstrated that, in the plasma from pregnant women, only one of the four CpG sites displays a decrease in DNA methylation compared with non-pregnant women. It indicates that this CpG site might be useful for determining the presence or absence of fetal wild-type alpha-globin gene cluster allele in maternal plasma. PMID- 29795671 TI - Xenotransplantation of adult hippocampal neural progenitors into the developing zebrafish for assessment of stem cell plasticity. AB - Adult stem cells are considered multipotent, restricted to differentiate into a few tissue-specific cell types. With the advent of technologies which can dedifferentiate and transdifferentiate cell types, assumptions about the process of cell fate determination must be reconsidered, including the role of extrinsic versus intrinsic factors. To determine the plasticity of adult neural progenitors, rat hippocampal progenitor cells were xenotransplanted into embryonic zebrafish. These animals allow for easy detection of transplanted cells due to their external development and transparency at early stages. Adult neural progenitors were observed throughout the zebrafish for the duration of the experiment (at least five days post-transplantation). While the majority of transplanted cells were observed in the central nervous system, a large percentage of cells were located in superficial tissues. However, approximately one-third of these cells retained neural morphology and expression of the neuronal marker, Class III beta-tubulin, indicating that the transplanted adult neural progenitors did not adapt alternate fates. A very small subset of cells demonstrated unique, non-neural flattened morphology, suggesting that adult neural progenitors may exhibit plasticity in this model, though at a very low rate. These findings demonstrate that the developing zebrafish may be an efficient model to explore plasticity of a variety of adult stem cell types and the role of external factors on cell fate. PMID- 29795672 TI - Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection. AB - BACKGROUND AND AIMS: Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-alpha plasma levels were also evaluated. METHODS: sCD163, sCD14 and TNF-alpha were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. RESULTS: At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-alpha levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-alpha levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. CONCLUSIONS: These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection. PMID- 29795673 TI - Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches. AB - Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds. This was achieved by following different strategies, including changing the growth conditions, heterologous expression of the cluster and inactivating the adpAa or overexpressing the abrC3 global regulatory genes. In addition, three new carotenoid compounds have been identified. PMID- 29795674 TI - Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian evolution. AB - MicroRNAs (miRNAs) are short, endogenous RNAs that post-transcriptionally repress mRNAs. Over the course of evolution, many new miRNAs are known to have emerged and added to the existing miRNA repertoires of drosophilids and vertebrates. Despite the large number of miRNAs in existence, the complementary pairing of only ~7 bases between miRNAs and mRNAs is sufficient to induce repression. Thus, miRNA targeting is so widespread that genes coexpressed with a miRNA have evolved to avoid sites that are targeted by the miRNA. Besides this avoidance, little is known about the preferential modes of miRNA targeting. Therefore, to elucidate miRNA targeting preference and avoidance, we evaluated the bias of the number of miRNA targeting occurrences in relation to expression intensities of miRNAs and their coexpressed target mRNAs by surveying transcriptome data from human organs. We found that miRNAs preferentially target genes with intermediate levels of expression, while avoiding highly expressed ones, and that older miRNAs have greater targeting specificity, suggesting that specificity increases during the course of evolution. PMID- 29795675 TI - Correction: Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study. AB - [This corrects the article DOI: 10.1371/journal.pone.0194697.]. PMID- 29795676 TI - WASH activities at two Ebola treatment units in Sierra Leone. AB - PURPOSE: The 2014 outbreak of Ebola virus disease (EVD) in West Africa was the largest in history. Starting in September 2014, International Medical Corps (IMC) operated five Ebola treatment units (ETUs) in Sierra Leone and Liberia. This paper explores how future infectious disease outbreak facilities in resource limited settings can be planned, organized, and managed by analyzing data collected on water, sanitation, and hygiene (WASH) and infection prevention control (IPC) protocols. DESIGN/METHODOLOGY/APPROACH: We conducted a retrospective cohort study by analyzing WASH/IPC activity data routinely recorded on paper forms or white boards at ETUs during the outbreak and later merged into a database from two IMC-run ETUs in Sierra Leone between December 2014 and December 2015. FINDINGS: The IMC WASH/IPC database contains data from over 369 days. Our results highlight parameters key to designing and maintaining an ETU. High concentration chlorine solution usage was highly correlated with both daily patient occupancy and high-risk zone staff entries; low concentration chlorine usage was less well explained by these measures. There is high demand for laundering and disinfecting of personal protective equipment (PPE) on a daily basis and approximately 1 (0-4) piece of PPE is damaged each day. RESEARCH LIMITATIONS/IMPLICATIONS: Lack of standardization in the type and format of data collected at ETUs made constructing the WASH/IPC database difficult. However, the data presented here may help inform humanitarian response operations in future epidemics. PMID- 29795677 TI - Intra-host and intra-household diversity of influenza A viruses during household transmissions in the 2013 season in 2 peri-urban communities of South Africa. AB - Limited information is available on influenza virus sequence drift between transmission events. In countries with high HIV burdens, like South Africa, the direct and indirect effect of HIV on influenza sequence drift between transmission events may be of public health concern. To this end, we measured hemagglutinin sequence diversity between influenza transmission events using data and specimens from a study investigating household transmission dynamics of seasonal influenza viruses in 2 peri-urban communities in South Africa during the 2013 influenza season. Thirty index cases and 107 of 110 eligible household contacts were enrolled into the study, 47% (14/30) demonstrating intra-household laboratory-confirmed influenza transmission. In this study 35 partial hemagglutinin gene sequences were obtained by Sanger sequencing from 11 index cases (sampled at enrolment only) and 16 secondary cases (8 cases sampled at 1 and 8 cases sampled at 2 time-points). Viral sequence identities confirmed matched influenza transmission pairs within the 11 households with corresponding sequenced index and secondary cases. Phylogenetic analysis revealed 10 different influenza viral lineages in the 14 households. Influenza A(H1N1)pdm09 strains were shown to be genetically distinct between the 2 communities (from distinct geographic regions), which was not observed for the influenza A(H3N2) strains. Intra-host/intra-household influenza A(H3N2) sequence drift was identified in 2 households. The first was a synonymous mutation between the index case and a household contact, and the second a non-synonymous mutation between 2 serial samples taken at days 0 and 4 post enrolment from an HIV-infected secondary case. Limited inter-household sequence diversity was observed as highlighted by sharing of the same influenza strain between different households within each community. The limited intra-household sequence drift is in line with previous studies also using Sanger sequencing, corroborating the presence of strict selective bottlenecks that limit sequence variance. We were not able to directly ascertain the effect of HIV on influenza sequence drift between transmission events. PMID- 29795679 TI - Correction: Estimating population extinction thresholds with categorical classification trees for Louisiana black bears. AB - [This corrects the article DOI: 10.1371/journal.pone.0191435.]. PMID- 29795678 TI - Effect of socioeconomic status on behavioral problems from preschool to early elementary school - A Japanese longitudinal study. AB - PURPOSE: Social inequalities are widely accepted to have a deleterious effect on children's mental health, and those with lower socioeconomic status generally experience more mental health issues. In this study, we examine the impact of socioeconomic situations of children's families during their early childhood on the children's social adaptation in Japanese elementary school. METHODS: The current investigation consisted of two sets of data relating to two separate years (with a one-year interval). The participants included preschoolers aged five years at Time 1 (the first year) and first graders aged six years at Time 2 (the second year); 1,712 met the inclusion criteria for both years. Parents of the participants completed a self-reported questionnaire regarding their SES (i.e., family economy and mother's education) and their children's mental health. Mental health was assessed using the Child Behavior Checklist/4-18, Parent Report. RESULTS: For each SES indicator, we found an inverse relationship across all the symptom dimensions. Specifically, bivariate analyses revealed that lower family income, maternal education level, and paternal education level predict all three domains of behavioral problems (i.e., internalized problems, externalized problems, and total behavioral problems). Further, multivariate analyses revealed that lower family income consistently predicts all domains of behavioral problems, lower maternal education level predicted externalized problems and total behavioral problems, and paternal education level did not predict any clinically significant behavioral problems. CONCLUSION: In this sample, we found that, for children, family income and parental education when entering preschool were significant predictors of mental health problems after elementary school enrollment; in particular, low income and low maternal educational achievement predicted a high probability of the development of a psychiatric disorder. A greater understanding of the mechanisms of these associations could contribute to improvements in interventions aimed at preventing child maladjustment. PMID- 29795680 TI - Genomic structure, expression, and functional characterization of checkpoint kinase 1 from Penaeus monodon. AB - Chk1 is a cell-cycle regulator. Chk1 has been identified in organisms ranging from yeast to humans, but few researchers have studied Chk1 in shrimps. We cloned Chk1 from the black tiger shrimp (Penaeus monodon). The full-length cDNA sequence of PmChk1 had 3,334 base pairs (bp), with an open reading frame of 1,455 bp. The complete genomic sequence of PmChk1 (11,081 bp) contained 10 exons separated by nine introns. qRT-PCR showed that PmChk1 was highly expressed in the ovaries and gills of P. monodon. The lowest PmChk1 expression was noted in stage III of ovarian development in P. monodon. PmChk1 expression decreased significantly after injection of 5-hydroxytryptamine and eyestalk ablation in P. monodon ovaries. RNA interference experiments were undertaken to examine the expression of PmChk1, PmCDC2, and PmCyclin B. PmChk1 knockdown in the ovaries and hepatopancreas by dsRNA-Chk1 was successful. The localization and level of PmChk1 expression in the hepatopancreas was studied using in situ hybridization, which showed that data were in accordance with those of qRT-PCR. The Gonadosomatic Index of P. monodon after dsRNA-Chk1 injection was significantly higher than that after injection of dsRNA-GFP or phosphate-buffered saline. These data suggest that PmChk1 may have important roles in the ovarian maturation of P. monodon. PMID- 29795681 TI - Gonadal transcriptome analysis of hybrid triploid loaches (Misgurnus anguillicaudatus) and their diploid and tetraploid parents. AB - Hybrid triploid loaches (Misgurnus anguillicaudatus) were generated from natural tetraploid and diploid loaches. We studied the gonads of parents and offspring from direct and reciprocal crosses through histological and transcriptome analyses. The triploid offspring had inferior ability to form sperm and egg cells compared with diploid forms. After sequencing the transcriptomes, 655,109,158 clean reads were obtained, and 62,821 unigenes and 178,962 transcripts were assembled. Of these unigenes, 23,189 were annotated in the GO database, 18,525 in the KEGG database and 24,661 in the KOG database. 36 fertility-related genes were found to be differentially expressed between the direct cross (2n * 4n) progenies and their parents, while 53 fertility-related genes between the reciprocal cross (4n * 2n) progenies and their parents. Following protein-protein interaction network analyses, 54 differentially expressed genes, including PLCB4, cyp17a1 and Pla2g4d, were mined, yielding candidate genes involved in the poor fertility of hybrid triploid loaches. This is the first report of transcriptomes of gonads of hybrid triploid loaches and their parents, offering a substantial contribution to sequence resources for this species and providing a deep insight into the molecular mechanism controlling the fertility of hybrid triploid fish. PMID- 29795683 TI - The use of an active learning approach in a SCALE-UP learning space improves academic performance in undergraduate General Biology. AB - Active learning is a pedagogical approach that involves students engaging in collaborative learning, which enables them to take more responsibility for their learning and improve their critical thinking skills. While prior research examined student performance at majority universities, this study focuses on specifically Historically Black Colleges and Universities (HBCUs) for the first time. Here we present work that focuses on the impact of active learning interventions at Florida A&M University, where we measured the impact of active learning strategies coupled with a SCALE-UP (Student Centered Active Learning Environment with Upside-down Pedagogies) learning environment on student success in General Biology. In biology sections where active learning techniques were employed, students watched online videos and completed specific activities before class covering information previously presented in a traditional lecture format. In-class activities were then carefully planned to reinforce critical concepts and enhance critical thinking skills through active learning techniques such as the one-minute paper, think-pair-share, and the utilization of clickers. Students in the active learning and control groups covered the same topics, took the same summative examinations and completed identical homework sets. In addition, the same instructor taught all of the sections included in this study. Testing demonstrated that these interventions increased learning gains by as much as 16%, and students reported an increase in their positive perceptions of active learning and biology. Overall, our results suggest that active learning approaches coupled with the SCALE-UP environment may provide an added opportunity for student success when compared with the standard modes of instruction in General Biology. PMID- 29795682 TI - Implicit-solvent dissipative particle dynamics force field based on a four-to-one coarse-grained mapping scheme. AB - A new set of efficient solvent-free dissipative particle dynamics (DPD) force fields was developed for phospholipids and peptides. To enhance transferability, this model maps around four heavy atoms and their connected hydrogen atoms into a coarse-grained elementary bead based on functional group. The effective hybrid potential between any pair of beads is composed of a short-range repulsive soft core potential that directly adopts the form of an explicit-solvent DPD model and a long-range attractive hydrophobic potential. The parameters of the attractive potentials for lipid molecules were obtained by fitting the explicit-solvent DPD simulation of one bead of any type in a water box, then finely tuning it until the bilayer membrane properties obtained in the explicit-solvent model were matched. These parameters were further extended to amino acids according to bead type. The structural and elastic properties of bilayer membranes, free energy profiles for a lipid flip-flop and amino acid analogues translocating across the membrane, and membrane pore formation induced by antimicrobial peptides obtained from this solvent-free DPD force field considerably agreed with the explicit solvent DPD results. Importantly, the efficiency of this method is guaranteed to accelerate the assembly of vesicles composed of several thousand lipids by up to 50-fold, rendering the experimental liposome dynamics as well as membrane-peptide interactions feasible at accessible computational expense. PMID- 29795684 TI - Correction: Prosocial Behavior and Subjective Insecurity in Violent Contexts: Field Experiments. AB - [This corrects the article DOI: 10.1371/journal.pone.0158878.]. PMID- 29795685 TI - A time series of urban extent in China using DSMP/OLS nighttime light data. AB - Urban extent data play an important role in urban management and urban studies, such as monitoring the process of urbanization and changes in the spatial configuration of urban areas. Traditional methods of extracting urban-extent information are primarily based on manual investigations and classifications using remote sensing images, and these methods have such problems as large costs in labor and time and low precision. This study proposes an improved, simplified and flexible method for extracting urban extents over multiple scales and the construction of spatiotemporal models using DMSP/OLS nighttime light (NTL) for practical situations. This method eliminates the regional temporal and spatial inconsistency of thresholding NTL in large-scale and multi-temporal scenes. Using this method, we have extracted the urban extents and calculated the corresponding areas on the county, municipal and provincial scales in China from 2000 to 2012. In addition, validation with the data of reference data shows that the overall accuracy (OA), Kappa and F1 Scores were 0.996, 0.793, and 0.782, respectively. We increased the spatial resolution of the urban extent to 500 m (approximately four times finer than the results of previous studies). Based on the urban extent dataset proposed above, we analyzed changes in urban extents over time and observed that urban sprawl has grown in all of the counties of China. We also identified three patterns of urban sprawl: Early Urban Growth, Constant Urban Growth and Recent Urban Growth. In addition, these trends of urban sprawl are consistent with the western, eastern and central cities of China, respectively, in terms of their spatial distribution, socioeconomic characteristics and historical background. Additionally, the urban extents display the spatial configurations of urban areas intuitively. The proposed urban extent dataset is available for download and can provide reference data and support for future studies of urbanization and urban planning. PMID- 29795687 TI - Eye movements and postural control in dyslexic children performing different visual tasks. AB - The aim of this study was to examine eye movements and postural control performance among dyslexic children while reading a text and performing the Landolt reading task. Fifteen dyslexic and 15 non-dyslexic children were asked to stand upright while performing two experimental visual tasks: text reading and Landolt reading. In the text reading task, children were asked to silently read a text displayed on a monitor, while in the Landolt reading task, the letters in the text were replaced by closed circles and Landolt rings, and children were asked to scan each circle/ring in a reading-like fashion, from left to right, and to count the number of Landolt rings. Eye movements (Mobile T2(r), SuriCog) and center of pressure excursions (Framiral(r), Grasse, France) were recorded. Visual performance variables were total reading time, mean duration of fixation, number of pro- and retro-saccades, and amplitude of pro-saccades. Postural performance variable was the center of pressure area. The results showed that dyslexic children spent more time reading the text and had a longer duration of fixation than non-dyslexic children. However, no difference was observed between dyslexic and non-dyslexic children in the Landolt reading task. Dyslexic children performed a higher number of pro- and retro-saccades than non-dyslexic children in both text reading and Landolt reading tasks. Dyslexic children had smaller pro saccade amplitude than non-dyslexic children in the text reading task. Finally, postural performance was poorer in dyslexic children than in non-dyslexic children. Reading difficulties in dyslexic children are related to eye movement strategies required to scan and obtain lexical and semantic meaning. However, postural control performance, which was poor in dyslexic children, is not related to lexical and semantic reading requirements and might not also be related to different eye movement behavior. PMID- 29795688 TI - Correction: Self-assembly and clustering of magnetic peapod-like rods with tunable directional interaction. AB - [This corrects the article DOI: 10.1371/journal.pone.0195552.]. PMID- 29795686 TI - beta2-microglobulin induces depressive- and anxiety-like behaviors in rat. AB - beta2-microglobulin (B2M), the light chain of major histocompatibility complex class I (MHC I) molecules, has been found to impair hippocampal neurogenesis. Based on the crucial role of hippocampal neurogenesis disturbance in the process of depression and anxiety, the aim of the present study is to investigate whether B2M leads to depressive- and anxiety-like behaviors. We found that 6 days after intracerebroventricular injection with B2M (0.3 MUg), the immobility times of rats in the tail suspension test and the forced swimming test were increased, the swimming and climbing time in the forced swimming test was decreased, and the latency to feed in the novelty-suppressed feeding test was increased, indicating that B2M induces depressive-like behaviors. In addition, in the elevated plus maze test, B2M-treated rats displayed obvious decline in the number of entries into and the proportion of time spent in the open arm, while the number of total arm entries was no change, which indicated that B2M induces anxiety-like behaviors. Our present findings suggest that target B2M might represent a novel approach for treatment of depression and anxiety. PMID- 29795689 TI - Feasibility and outcomes of atrial fibrillation screening using intermittent electrocardiography in a primary healthcare setting: A cross-sectional study. AB - BACKGROUND: Atrial fibrillation (AF) is a major risk factor for ischemic stroke unless treated with an anticoagulant. Detecting AF can be difficult because AF is often paroxysmal and asymptomatic. The aims of this study were to develop a screening model to detect AF in a primary healthcare setting and to initiate oral anticoagulant therapy in high-risk patients to prevent stroke. METHODS: This was a cross-sectional study. All 70- to 74-year-old individuals registered at a single primary healthcare center in Stockholm were invited to participate in AF screening upon visiting the center during a ten-month period. Those who did not have contact with the center during this period were invited to participate by letter. Thirty-second intermittent ECG recordings were made twice a day using a handheld Zenicor device over a 2-week period in participants without AF. Oral anticoagulant therapy was offered to patients with newly detected AF. FINDINGS: Of the 415 eligible individuals, a total of 324 (78.1%) patients participated in the study. The mean age of the participants was 72 years, 52.2% were female, and the median CHA2DS2-VASc score of the participants was 3. In the target population, 34 (8.2%) individuals had previously diagnosed AF. Among participants without previously known AF, 16 (5.5%) cases of AF were detected. The final AF prevalence in the target population was 12%. Oral anticoagulant therapy was successfully initiated in 88% of these patients with newly detected AF. CONCLUSIONS: The AF screening project exhibited a high participation rate and resulted in a high rate of newly discovered AF; of these newly diagnosed patients, 88% could be treated with an oral anticoagulant. PMID- 29795691 TI - Reconsidering non-traditional export agriculture and household food security: A case study in rural Guatemala. AB - As the production of non-traditional export (NTX) crops by smallholder households in developing countries expands, there is a compelling need to understand the potential effects of this type of agricultural production on household food security and nutrition. We use two household surveys with a sample of 52 households, interviews, and focus groups to examine whether smallholder farmers who produce broccoli for export in a rural Guatemalan community have different household food security than farmers in the same community who are still growing traditional maize and bean crops. We explore and compare the food security status of broccoli farmers (adopters) and traditional farmers (non-adopters) across four dimensions of food security: availability, access, utilization, and stability. Adopters earned significantly more income (40%) than non-adopters, but higher incomes did not coincide with improvements in food availability, food access, or food utilization. Results indicate that adopters and non-adopters alike struggle with access to food, while the intensity of broccoli production may be undermining the ability of local agricultural systems to naturally control pests and regulate nutrients. More systematic approaches to food security assessment, especially those that consider all four dimensions of food security, are needed to better target interventions designed to alleviate food insecurity among rural smallholders. PMID- 29795690 TI - The weekend effect in liver transplantation. AB - BACKGROUND: The weekend effect describes a phenomenon whereby patients admitted to hospitals on weekends are at higher risk of complications compared to those admitted during weekdays. However, if a weekend effect exists in orthotopic liver transplantation (oLT). METHODS: We analyzed oLT between 2006 and 2016 and stratified patients into weekday (Monday to Friday) and weekend (Saturday, Sunday) groups. Primary outcome measures were one-year patient and graft survival. RESULTS: 364 deceased donor livers were transplanted into 329 patients with 246 weekday (74.77%) and 83 weekend (25.23%) patients. Potential confounders (e.g. age, ischemia time, MELD score) were comparable. One-year patient and graft survival were similar. Frequencies of rejections, primary-non function or re transplantation were not different. The day of transplantation was not associated with one-year patient and graft survival in multivariate analysis. CONCLUSIONS: We provide the first data for the Eurotransplant region on oLT stratified for weekend and weekday procedures and our findings suggest there was no weekend effect on oLT. While we hypothesize that the absent weekend effect is due to standardized transplant procedures and specialized multidisciplinary transplant teams, our results are encouraging showing oLT is a safe and successful procedure, independent from the day of the week. PMID- 29795692 TI - Effect of combining inferior oblique muscle weakening procedures with exotropia surgery on the surgical correction of exotropia. AB - PURPOSE: To determine whether the inferior oblique (IO) muscle weakening procedure combined with exotropia surgery affects the surgical correction of exotropia. DESIGN: Institutional, retrospective study. METHODS: We retrospectively reviewed the medical records of 310 patients who had undergone exotropia-correcting surgery combined with IO weakening (group A, 64 patients) or without IO weakening (group B, 246) with a postoperative follow-up of 6 months or more. The main outcome measures were the postoperative mean angle of horizontal deviation, the success rate, and the overcorrection rate. Surgical success was defined as an alignment between 10 prism diopters (PD) of exodeviation and 5 PD of esodeviation. RESULTS: The postoperative mean angles of exodeviation, throughout the follow-up period, did not significantly differ between the groups. Although the surgical success rate was higher in group B at postoperative 1 month (p = 0.035), there was no statistical difference between the 2 groups from postoperative 6 months.: The final success rates were 56.3 and 51.6% (p = 0.509). The overcorrection rate was significantly higher in group A at postoperative 1, 6 and 24 months (p = 0.017, p = 0.028, p = 0.030, respectively); however, at the final follow-up, there was no overcorrection in either group. CONCLUSION: The overcorrection rate was higher in group A until postoperative 2 years, even though the mean angles of exodeviation and the success rates did not significantly differ between the 2 groups. Surgeons should be mindful of overcorrection when planning exotropia surgery combined with the IO weakening procedure. PMID- 29795693 TI - Correction: Latent tuberculosis infection in foreign-born communities: Import vs. transmission in The Netherlands derived through mathematical modelling. AB - [This corrects the article DOI: 10.1371/journal.pone.0192282.]. PMID- 29795694 TI - Correction: Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study. AB - [This corrects the article DOI: 10.1371/journal.pone.0192574.]. PMID- 29795695 TI - Student researchers' perceived prerequisites for voluntary research collaboration in the context of Flemish and Chinese universities. AB - While numerous papers have illuminated the worthiness of research collaboration, relatively few have addressed its prerequisites. In our study, seven prerequisites for research collaboration were extracted from the existing literature, and 460 student researchers were surveyed for their perceptions of the prerequisites' importance. Focusing on voluntary research collaborations rather than brokered ones, it was found that socially oriented prerequisites such as reciprocal interactions, accountability, trust, and equality are perceived of more importance than prerequisites of psychical proximity, networking channels, and funds and material supplies (substance- and entity-related prerequisites). With latent regression analyses, we also found that Chinese and older, more experienced researchers are inclined to stress the importance of equality. Researchers of different cohorts prioritise substance- and entity-related prerequisites disparately. Specifically, Chinese researchers emphasise the necessity of funds, while researchers from first-tier universities place more value on networking channels. Disciplinary differences for the prerequisite of proximity were also discovered. Based on these results, discussion and implications were referred. Further suggestions on research collaboration studies are rendered. PMID- 29795696 TI - Correction: Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach. AB - [This corrects the article DOI: 10.1371/journal.pone.0193138.]. PMID- 29795697 TI - Correction: Predicting anti-RhD titers in donors: Boostering response and decline rates are personal. AB - [This corrects the article DOI: 10.1371/journal.pone.0196382.]. PMID- 29795698 TI - Modeling of the HIV epidemic and continuum of care in French Guiana. AB - BACKGROUND: In order to compute the continuum of care for French Guiana, it is necessary to estimate the total number of persons living with HIV. The main objective was to determine how many persons were infected with HIV and how many were unaware of it. METHODS: We used 2 different models to calculate the total number of persons infected with HIV: Spectrum's AIM module using CSAVR to compute incidence from case registration and vital statistics; and the ECDC model from the French Guiana HIV cohort data. RESULT: The present results show that both models led to similar results regarding the incident number of cases (i.e. for 2016 174 versus 161) and the total HIV population (in 2016 3206 versus 3539) respectively. The ECDC modeling tool showed that the proportion of undiagnosed HIV infections declined from 50% in 1990 to 15% in 2015. This amounted to a stable or slightly increasing total number of undiagnosed patients of 520. CONCLUSIONS: The estimations of the total HIV population by both models show that the HIV population is still growing. The incidence rate declined in 2000 and the decline of the number of newly acquired HIV infections, after a decline after 2003 is offset by population growth. The proportion of undiagnosed infections has declined to 15% but the number of undiagnosed infections remains stable. The HIV cascade shows that despite good results for treatment in care, reaching the 90*90*90 UNAIDS target may be difficult because a significant proportion of patients are lost to follow-up. PMID- 29795699 TI - Correction: Biosorption of Cadmium and Manganese Using Free Cells of Klebsiella sp. Isolated from Waste Water. AB - [This corrects the article DOI: 10.1371/journal.pone.0140962.]. PMID- 29795701 TI - Correction: Octreotide modulates the expression of somatostatin receptor subtypes in inflamed rat jejunum induced by Cryptosporidium parvum. AB - [This corrects the article DOI: 10.1371/journal.pone.0194058.]. PMID- 29795700 TI - Fresh fruit consumption and risk of incident albuminuria among rural Chinese adults: A village-based prospective cohort study. AB - BACKGROUND: Recent studies showed that increased fresh fruit consumption is significantly associated with lower risks of diabetes, hypertension, and cardiovascular disease (CVD); other studies suggested that albuminuria is associated with diabetes, hypertension, and CVD. Therefore, we hypothesized that lower fresh fruit consumption is associated with higher risk of incident albuminuria among Chinese adults in rural areas, where fresh fruit consumption level is very low and prevalence of albuminuria is high. METHODS: We tested the hypothesis in a village-based cohort study of 3574 participants aged >= 30 years from the Handan Eye Study conducted from 2006 to 2013. Albuminuria was defined as urinary albumin-to-creatinine ratio >= 30 mg/g. RESULTS: Overall, 35.4% of the participants never or rarely consumed fresh fruits, and 33.9, 21.6, and 9.1% consumed fresh fruits 1-3 times/month, 1-2 times/week, and >= 3 times/week, respectively. During a median follow-up period of 5.6 years, albuminuria developed in 17.6% (n = 629) of the participants. Compared with participants who consumed fresh fruits >= 3 times/week, the multivariable adjustment odds ratios (ORs) for incident albuminuria associated with fruit consumption 1-2 times/week, 1-3 times/month, and no or rare consumption were 1.58 (95% confidence intervals (CI), 1.05-2.40), 1.74 (95% CI, 1.17-2.58), and 1.78 (95% CI, 1.20-2.64), respectively. After excluding participants with diabetes, the association remained significant. CONCLUSIONS: Lower fresh fruit consumption was significantly associated with higher risk of incident albuminuria, and fresh fruit consumption frequency could be an essential intervention target to prevent albuminuria in rural China. PMID- 29795702 TI - Tailoring the specificity of the type C feruloyl esterase FoFaeC from Fusarium oxysporum towards methyl sinapate by rational redesign based on small molecule docking simulations. AB - The type C feruloyl esterase FoFaeC from Fusarium oxysporum is a newly discovered enzyme with high potential for use in the hydrolysis of lignocellulosic biomass but it shows low activity towards sinapates. In this work, small molecule docking simulations were employed in order to identify important residues for the binding of the four model methyl esters of hydroxycinnamic acids, methyl ferulate/caffeate/sinapate/p-coumarate, to the predicted structure of FoFaeC. Subsequently rational redesign was applied to the enzyme' active site in order to improve its specificity towards methyl sinapate. A double mutation (F230H/T202V) was considered to provide hydrophobic environment for stabilization of the methoxy substitution on sinapate and a larger binding pocket. Five mutant clones and the wild type were produced in Pichia pastoris and biochemically characterized. All clones showed improved activity, substrate affinity, catalytic efficiency and turnover rate compared to the wild type against methyl sinapate, with clone P13 showing a 5-fold improvement in catalytic efficiency. Although the affinity of all mutant clones was improved against the four model substrates, the catalytic efficiency and turnover rate decreased for the substrates containing a hydroxyl substitution. PMID- 29795703 TI - Position specific player load during match-play in a professional football club. AB - There is a rapid growing body of knowledge regarding physical aspects of a football match due to studies using computer-assisted motion analysis. The present study used time-motion analysis and triaxial-accelerometers to obtain new insights about differences in physical profiles of elite football players across playing-positions. Player performance data in 23 official home matches from a professional football club, during two seasons were collected for analysis. Eighteen players from five different playing positions (central backs: n = 3; full-backs: n = 5; central midfielders: n = 6; wide midfielders: n = 3; and central forwards: n = 4), performing a total of 138 observations. A novel finding was that central backs and central midfielders had significantly lower work-rate in sprints, decelerations and accelerations than full-backs, wide midfielders and central forwards (p<0.001). Furthermore, wide midfielders and full-backs performed significantly more turns (>90 degrees ) than central backs. The most common distance covered in high-intensity runs (>=19.8 km.h-1) for central backs, central midfielders, wide midfielders and central forwards was 1-5 m, but for full-backs was 6-10 m. This may help coaches in developing individualized training programs to meet the demands of each position in match-play. PMID- 29795705 TI - Beyond degree and betweenness centrality: Alternative topological measures to predict viral targets. AB - The availability of large-scale screens of host-virus interaction interfaces enabled the topological analysis of viral protein targets of the host. In particular, host proteins that bind viral proteins are generally hubs and proteins with high betweenness centrality. Recently, other topological measures were introduced that a virus may tap to infect a host cell. Utilizing experimentally determined sets of human protein targets from Herpes, Hepatitis, HIV and Influenza, we pooled molecular interactions between proteins from different pathway databases. Apart from a protein's degree and betweenness centrality, we considered a protein's pathway participation, ability to topologically control a network and protein PageRank index. In particular, we found that proteins with increasing values of such measures tend to accumulate viral targets and distinguish viral targets from non-targets. Furthermore, all such topological measures strongly correlate with the occurrence of a given protein in different pathways. Building a random forest classifier that is based on such topological measures, we found that protein PageRank index had the highest impact on the classification of viral (non-)targets while proteins' ability to topologically control an interaction network played the least important role. PMID- 29795706 TI - Relative Suffix Trees. AB - Suffix trees are one of the most versatile data structures in stringology, with many applications in bioinformatics. Their main drawback is their size, which can be tens of times larger than the input sequence. Much effort has been put into reducing the space usage, leading ultimately to compressed suffix trees. These compressed data structures can efficiently simulate the suffix tree, while using space proportional to a compressed representation of the sequence. In this work, we take a new approach to compressed suffix trees for repetitive sequence collections, such as collections of individual genomes. We compress the suffix trees of individual sequences relative to the suffix tree of a reference sequence. These relative data structures provide competitive time/space trade offs, being almost as small as the smallest compressed suffix trees for repetitive collections, and competitive in time with the largest and fastest compressed suffix trees. PMID- 29795704 TI - A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii. AB - The nosocomial pathogen Acinetobacter baumannii is a significant threat due to its ability to cause infections refractory to a broad range of antibiotic treatments. We show here that a highly conserved sensory-transduction system, BfmRS, mediates the coordinate development of both enhanced virulence and resistance in this microorganism. Hyperactive alleles of BfmRS conferred increased protection from serum complement killing and allowed lethal systemic disease in mice. BfmRS also augmented resistance and tolerance against an expansive set of antibiotics, including dramatic protection from beta-lactam toxicity. Through transcriptome profiling, we showed that BfmRS governs these phenotypes through global transcriptional regulation of a post-exponential-phase like program of gene expression, a key feature of which is modulation of envelope biogenesis and defense pathways. BfmRS activity defended against cell-wall lesions through both beta-lactamase-dependent and -independent mechanisms, with the latter being connected to control of lytic transglycosylase production and proper coordination of morphogenesis and division. In addition, hypersensitivity of bfmRS knockouts could be suppressed by unlinked mutations restoring a short, rod cell morphology, indicating that regulation of drug resistance, pathogenicity, and envelope morphogenesis are intimately linked by this central regulatory system in A. baumannii. This work demonstrates that BfmRS controls a global regulatory network coupling cellular physiology to the ability to cause invasive, drug-resistant infections. PMID- 29795708 TI - Barriers and facilitators for access to mental health services by traumatized youth. AB - Polytrauma is a highly prevalent public health problem in the U.S. with even higher rates in urban areas. Children with polytrauma often end up in multiple child-serving systems (e.g., mental health, child welfare, education, juvenile justice) with needs that are both complex and severe. Providers within these child-serving systems have potential to serve as gatekeepers to trauma services by linking youth with trauma-informed treatments and supports that promote recovery. The purpose of our study was to assess the perspective of providers who participated in a nine-month, trauma-informed care (TIC) training intervention on 1) their capacity to make referrals to trauma-specific services following the training, and 2) factors external to the training intervention that supported or hindered their ability to link traumatized youth with services. A subset of sixteen participants from the TIC training completed individual interviews. These participants were predominantly female, African American, and based in the social services sector. The constant comparative method was used to derive three thematic domains related to participant perceptions regarding youth referrals: 1) Organizational and provider capacity to provide trauma treatment or to make referrals to trauma-specific services, 2) Barriers to youth accessing trauma services, and 3) Suggestions for improving coordination of care and referrals. Our study highlights the influence of contextual factors on whether a TIC training can improve the capacity of agencies and individual providers to support traumatized youth in accessing appropriate services. The development of a structure that formally connects youth-serving agencies and providers with specialists trained in addressing traumatized youth is recommended. PMID- 29795710 TI - Generalized Confidence Intervals Compatible with the Min Test for Simultaneous Comparisons of One Subpopulation to Several Other Subpopulations. AB - A problem where one subpopulation is compared to several other subpopulations in terms of means with the goal of estimating the smallest difference between the means commonly arises in biology, medicine, and many other scientific fields. A generalization of Strassburger, Bretz and Hochberg (2004) approach for two comparisons is presented for cases with three and more comparisons. The method allows constructing an interval-estimator for the smallest mean difference, which is compatible with the Min test. An application to a fluency-disorder study is illustrated. Simulations confirmed adequate probability coverage for normally distributed outcomes for a number of designs. PMID- 29795707 TI - Cognitive Decline as a Result of Incarceration and the Effects of a CBT/MT Intervention: A Cluster-Randomized Controlled Trial. AB - This study primarily tests whether incarceration negatively affects cognitive functioning; namely emotion regulation, cognitive control, and emotion recognition. As a secondary interest, we test protective effects of a Cognitive Behavioral Therapy/Mindfulness Training (CBT/MT) intervention. Dormitories containing 197 incarcerated males aged 16-18 were randomly assigned to either a CBT/MT program or an active control condition. A cognitive task was administered pre-treatment and again four months later, upon treatment completion. Performance on all outcome variables was significantly worse at follow-up compared to baseline. There were marginally significant group by time interactions. While the control group performance significantly declined in both cognitive control and emotion regulation, the CBT/MT group showed no significant decline in either outcome. This is the first study to probe the effects of incarceration on these three processes. Findings suggest that incarceration worsens a known risk factor for crime (cognitive functioning), and that a CBT/MT intervention may help buffer against declines. PMID- 29795712 TI - "It's ok if it's hidden": The discursive construction of everyday racism for refugees and asylum seekers in Wales. AB - Wales has a long history of migration; however, the introduction of dispersed asylum seekers in 2001 has led to Wales becoming a more superdiverse nation. Wales has often been positioned as a more "tolerant nation" than England; however, the increasingly superdiverse nature of Wales in a postdevolution era may now be calling this tolerance thesis into question. Models of refugee and asylum seeker integration suggest that the absence of racism plays a key role in integration. This paper reports the findings of research that centres on refugee and asylum seeker integration in Wales. Nineteen interviews were conducted with refugees and asylum seekers who had been living in Wales for between 1 month and 12 years. Each interview was analysed using a discursive psychology approach. In this paper, I show that the interviewees appeared to negotiate a dilemma when talking about experiencing potentially racist incidents within the interviews, constructing them as trivial so as not to appear critical of the protection they have received in Wales. The findings also highlight the more everyday and banal forms of racism that are regularly experienced by refugees and asylum seekers living in Wales. PMID- 29795709 TI - Child Care and Cortisol Across Infancy and Toddlerhood: Poverty, Peers, and Developmental Timing. AB - Evidence suggests that relations between child care and children's development behaviorally and physiologically-likely differ between children from high-versus low-risk contexts. Using data from the Family Life Project (N = 1,155), the authors tested (a) whether within- and between-child differences in children's child care experiences (i.e., quantity, type, caregiver responsivity, and peer exposure) were predictive of their cortisol levels across infancy and toddlerhood and (b) whether these relations differed for children experiencing different levels of environmental risk. They found some evidence of such interactive effects. For children from high-risk contexts, within-child increases in child care hours were predictive of cortisol decreases. The inverse was evident for children from low-risk contexts. This relation grew across toddlerhood. Whereas a history of greater center-based child care was predictive of heightened cortisol levels for low-risk families, this was not the case for children from high-risk families. Irrespective of risk, greater peer exposure (between children) was associated with lower cortisol levels. PMID- 29795713 TI - Editorial: Add-on Tests. PMID- 29795711 TI - Growth in inhibitory control among low-income, ethnic-minority preschoolers: A group-based modeling approach. AB - The emergence of self-regulation skills such as inhibitory control in children is an important developmental process associated with adjustment across multiple domains. Individual differences in inhibitory control are associated with family socioeconomic status but have not been studied in relation to variations in risk found within a low-income (i.e., high risk) sample (N = 407). Using a group-based modeling approach, change in inhibitory control was examined from 30 to 42 months of age in a sample of low-income Hispanic and African-American children. Patterns of change in inhibitory control were examined in relation to cumulative risk and child externalizing behavior using the Child Behavior Checklist measured at 42 months. A three-group solution was identified as optimally fitting the data, representing patterns of change in inhibitory control: a normative group, exhibiting increasing inhibitory control (48%); a low-stable group (40%); and a high-stable group (12%). Group membership did not differ by child ethnicity or gender. Higher cumulative risk was found among the children in the low-stable group than in the other groups. Mothers reported more externalizing problems at 42 months for children in the low-stable group than in the other groups, even controlling for the effect of cumulative risk. Intervention and policy implications are discussed. PMID- 29795714 TI - The Role of Matrix Metalloproteinase-3 In the Development of Atherosclerosis and Cardiovascular Events. AB - The matrix metalloproteinases are a family of peptidase enzymes responsible for the degradation of extracellular matrix (ECM). Alterations in the structure and composition of the ECM play a key role in the atherogenic process. Recent data suggest the important role of MMPs in the development of atherosclerosis and future cardiovascular events. Expressed at low levels in normal tissue, MMPs are upregulated in remodeling processes. Matrix metalloproteinase-3 (MMP-3) is present in atherosclerotic plaques and acts in the degradation of the fibrous cap of the atheroma. Many clinical studies reported that increased MMP-3 level and also the gene polymorphism of MMP were the independent cardiovascular risk factors. MMPs represent an attractive target to prevent matrix degradation, atherosclerosis and possible cardiovascular events. PMID- 29795715 TI - Bio-Metrological Uncertainty In Clinical Laboratory Sciences. PMID- 29795716 TI - Association of C-Reactive Protein and Other Markers of Inflammation with Risk of Complications in Diabetic Subjects. AB - The inflammatory process and factors that contribute to chronic low-grade inflammation have recently become a focus in cardiovascular disease, diabetes, peripheral vascular diseases, renal disease and hypertension. The aim of this article was to discuss on the clinical utility of C-reactive protein and several other inflammatory molecules in diabetic patients. PMID- 29795717 TI - Sequencing of Von Hippel-Lindau (VHL) Gene from Genomic DNA for Mutation Detection in Italian Patients. AB - Genomic DNA from patients suspected to have VHL were analysed by direct sequencing of the VHL gene-coding region for mutation detection. Sequencing was performed on the extracted DNA following amplification by Polymerase Chain Reaction (PCR) with suitably designed primers. Genetic analysis revealed a single base substitution in exon 3 of each of the two patients causing the R161X (stop codon) being a de novo mutation and the R176W missense mutation, respectively. The genetic and familial studies indicated that the VHL disease is inherited as a dominant trait. PMID- 29795718 TI - Immunophenotyping of Peripheral Blood and Bone Marrow Cells by Flow Cytometry. PMID- 29795720 TI - Ruthenium brachytherapy for intraocular growth of a conjunctival squamous cell carcinoma: a case report. AB - The aim of this study is to report the use of ruthenium brachytherapy as an adjunctive treatment in the management of an intraocular extension of the conjunctival squamous cell carcinoma (SCC). In 2013, a 73-year-old man presented with a tumor blocking the angle and infiltrating corneal endothelium. The patient was treated with iridectomy, and after one month, ruthenium brachytherapy was applied. 4.5 years post-irradiation, the treated eye is painless, and no recurrence was noted. We advocate the use of ruthenium brachytherapy as an eye salvage treatment with an intraocular extension of conjunctival SCC. PMID- 29795721 TI - Comparison of Varying Heel to Toe Differences and Cushion to Barefoot Running in Novice Minimalist Runners. AB - There are many different types of footwear available for runners in today's market. Many of these shoes claim to help runners run more efficiently by altering an individual's stride mechanics. Minimalist footwear claims to aid runners run more on their forefeet whereas more traditional footwear provides more cushioning specifically for a heel first landing. The purpose of this paper was to determine if runners, who were accustomed to running in traditional footwear would alter their running mechanics while running acutely in various types of minimalist footwear. Twelve subjects, accustomed to running in traditional 12 mm heel/toe differential footwear, ran in five footwear conditions on a treadmill at a controlled pace for two minutes after warming up in each condition for 5 minutes. While running in 12 mm heel/toe differential footwear compared to barefoot, subjects ran with a significantly longer ground time, a lower stride rate and greater vertical oscillation. There were not any differences in variables when running in the shod conditions despite the varying heel/toe differentials. Running barefoot proved to be different than running in traditional 12 mm drop cushioned footwear. PMID- 29795719 TI - Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of Human Decidua Basalis Mesenchymal Stem/Multipotent Stromal Cells. AB - Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from the decidua basalis (DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2 enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2 treatment displayed antiangiogenic activity. H2O2 preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL 1beta, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments. PMID- 29795722 TI - Acute Cardiovascular Responses after a Single Bout of Blood Flow Restriction Training. AB - Different types of exercise might produce reductions in blood pressure (BP). One physiological mechanism that could explain the lowering adaptation effect on BP after an exercise program is an improved in baroreflex control of muscle sympathetic nerve activity. Consequently, exploring the different methods of training and their post-exercise hypotension (PEH) becomes of interest for healthcare providers. Recently, it has been suggested that blood flow restriction training (BFR) can generate PEH. The aim of this study was to determine the acute response on cardiovascular variables after low intensity resistance training with BFR in normotensive subjects. Twenty-four male (24.38+/-3.88 years) performed four sets of plantar flexion at 30% 1RM (1*30 + 3*15 repetitions) with 30% of maximal occlusion pressure and 60 seconds resting period. The restrictive pressure was released during the intervals between sets. BP, heart rate (HR), blood oxygen saturation (SpO2) and double product (DP) were measured in baseline, after each set of exercise and 15, 30, 45, 60 minutes and 24 hours after exercise. An immediate significant increase across the set was observed for HR values (11.5%) (p<0.05) during application the protocol. SBP and DBP values also increased during exercise although mildly (1.7% and 1%, respectively) without significant differences compared with pre-values. A post-exercise hypotension was obtained 15min post-training (SBP: -6.9%; DBP: -3%). There was no significant change in SpO2 and DP during and post-exercise with BFR. Cardiovascular responses were altered mildly during BFR-training and after the single bout. In conclusion, BFR in young normotensive humans generated post-exercise hypotension. PMID- 29795723 TI - Serum Tumor Necrosis Factor-alpha associates with Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women. AB - The functional implications of serum tumor necrosis factor-alpha (TNF-alpha), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-alpha on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-alpha on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO2max). Large artery compliance was measured by pulse contour analyses while rate pressure product (RPP), an index of myocardial oxygen demand, was measured at rest and during two submaximal workloads (i.e., ~55% and ~75% VO2max). RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. During higher-intensity exertion, ~75% VO2max, multiple linear regression revealed a positive association (r = 0.43; p = 0.015) between TNF-alpha and RPP while adjusting for maximal heart rate, VO2max, large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-alpha, beta = 0.13, CI [0.03, 0.35], indicating greater levels of TNF-alpha associated with poorer exercise tolerance. These data suggest TNF-alpha independently associates with myocardial oxygen demand during physical exertion, thus highlighting the utility of higher-intensity efforts to expose important phenomena not apparent at rest. TNF-alpha also appears to be indirectly associated with the link between large artery compliance and exercise tolerance. PMID- 29795724 TI - Effects of Strength Training Sessions Performed with Different Exercise Orders and Intervals on Blood Pressure and Heart Rate Variability. AB - This study compared the effect of a strength training session performed at different exercise orders and rest intervals on blood pressure and heart rate variability (HRV). Fifteen trained men performed different upper body exercise sequences [large to small muscle mass (SEQA) and small to large muscle mass (SEQB)] in randomized order with rest intervals between sets and exercises of 40 or 90 seconds. Fifteen repetition maximum loads were tested to control the training intensity and the total volume load. The results showed, significant reductions for systolic blood pressure (SBP) for all sequences compared to baseline and, post-exercise: SEQA90 at 20, 30, 40, 50 and 60 minutes; SEQA40 and SEQB40 at 20 minutes and SEQB90 at 10, 20, 30, 40, 50 and 60 minutes. For diastolic blood pressure (DBP), significant reductions were found for three sequences compared to baseline and, post-exercise: SEQA90 and SEQA40 at 50 and 60 minutes; SEQB40 at 10, 30 and 60 minutes. For HRV, there were significant differences in frequency domain for all sequences compared to baseline. In conclusion, when performing upper body strength training sessions, it is suggested that 90 second rest intervals between sets and exercises promotes a post-exercise hypotensive response in SBP. The 40 second rest interval between sets and exercises was associated with greater cardiac stress, and might be contraindicated when working with individuals that exhibit symptoms of cardiovascular disease. PMID- 29795725 TI - The Short-Term Effects of Lying, Sitting and Standing on Energy Expenditure in Women. AB - The deleterious health effects of too much sitting have been associated with an increased risk for overweight and obesity. Replacing sitting with standing is the proposed intervention to increase daily energy expenditure (EE). The purpose of this study was to determine the short-term effects of lying, sitting, and standing postures on EE, and determine the magnitude of the effect each posture has on EE using indirect calorimetry (IC). Twenty-eight healthy females performed three separate positions (lying, sitting, standing) in random order. Inspired and expired gases were collected for 45-minutes (15 minutes for each position) using breath-by-breath indirect calorimetry. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured to estimate EE. Statistical analyses used repeat measures ANOVA to analyze all variables and post hoc t-tests. Based on the ANOVA the individual, time period and order term did not result in a statistically significant difference. Lying EE and sitting EE were not different from each other (P = 0.56). However, standing EE (kcal/min) was 9.0 % greater than lying EE (kcal/min) (P = 0.003), and 7.1% greater than sitting EE (kcal/min) (P = 0.02). The energetic cost of standing was higher compared to lying and sitting. While this is statistically significant, the magnitude of the effect of standing when compared to sitting was small (Cohen's d = 0.31). Short-term standing does not offer an energetic advantage when compared to sitting. PMID- 29795726 TI - An Evaluation of Select Physical Activity Exercise Classes on Bone Metabolism. AB - Weight-bearing physical activity can optimize bone mass early in life and prevent the development of osteoporosis. However, less is known about the potential benefits of non-weight-bearing activities. The purpose of this study was to assess the efficacy of structured physical activity classes on bone metabolism. Twenty-eight premenopausal women, aged 18-35 years who were either enrolled in a yoga class (n=14) or cardio-kickboxing class (n=14) voluntarily consented to participate. Both classes were introductory classes meeting twice per week for 50 min per session for 12 weeks. Anteroposterior spine (L1-L4), hip (dual femur), and total body bone mineral density (BMD) was measured in both groups pre and post intervention using dual-energy X-ray absorptiometry (DXA). Pre and post blood samples were drawn for measurement of serum osteocalcin (OC) by enzyme linked immunosorbent assay (ELISA) in each group. Baseline subject characteristics including age, height, weight, body fat percentage, and lean body mass did not differ between groups. BMD levels did not increase but were held stable over the course of the intervention. Yoga increased OC by 68% (P < 0.001) and cardio-kickboxing increased OC by 67% (P < 0.001) over the course of the 12 week classes. While 12 weeks of yoga and cardio-kickboxing were insufficient to induce BMD changes, OC levels reflect the bone formation process was initiated, but not yet complete. Increased OC levels suggest the selected physical activity classes provided enough of a stimulus to precipitate a future response of bone growth, assuming exercise training remains constant. PMID- 29795727 TI - The Effect of a Single Bout of High Intensity Intermittent Exercise on Glucose Tolerance in Non-diabetic Older Adults. AB - Our aim was to investigate the acute effects of a single bout of high intensity intermittent training (HIIT) on glucose tolerance and other physiological and metabolic markers in non-diabetic older adults. Fourteen healthy older adults (age, 64 +/- 2 y; BMI, 25.7 +/- 2.8 kg.m-2) performed two acute exercise trials: continuous moderate intensity exercise (MOD) and HIIT, with the response to an oral glucose tolerance test (OGTT) determined <24 hours after. Inflammatory, haematological, and lipid parameters were also assessed the day after each trial. There was an effect of the trials on the insulin response to an OGTT (P=0.047), but not the glucose response. Following an acute bout of HIIT, insulin concentration during an OGTT was elevated at 60 min compared to the control trial (P=0.045), indicating more insulin was secreted, but glucose concentration was unchanged in all trials. The study findings demonstrate that a single bout of HIIT affects the insulin response but not the glycaemic response to a glucose load, proffering a potential benefit for metabolic health in older adults. PMID- 29795728 TI - Effects of Single-Dose Dietary Nitrate on Oxygen Consumption During and After Maximal and Submaximal Exercise in Healthy Humans: A Pilot Study. AB - Dietary nitrate (NO3-) has been shown to reduce oxygen consumption (VO2) during moderate to high-intensity (e.g. time to fatigue, time trials) exercise and often in trained athletes. However, less is known regarding prolonged exercise and the potential impact of NO3- on post-exercise excess oxygen consumption (EPOC), particularly in untrained individuals, who may have different metabolic goals during exercise than trained individuals. We tested the hypothesis that acute nitrate supplementation in the form of beet root juice will significantly decrease both VO2 during maximal exercise and EPOC in both maximal and submaximal exercise trials. Eight young, moderately active, healthy males (age: 24.8+/-1.4 years, body mass index: 23.7+/-0.4 kg/m2; VO2max: 34.2+/-3.9 ml/kg/min) performed step-wise maximal cycle exercise (n=4) and prolonged submaximal cycle exercise (n=6) (45 min; 38+/-2% of max work rate) in control (anti-bacterial mouthwash) and acute NO3- supplemented conditions [70ml concentrated beet root juice (0.4g NO3-), 2 hrs prior to exercise] on separate occasions. Measurements of VO2 (indirect calorimetry), arterial blood pressure (MAP; sphygmomanometry), and heart rate (HR; ECG) were made before, during, and following exercise bouts. NO3- reduced MAP at rest ~1-3mmHg. However, NO3- had no impact on VO2 during maximal (VO2max, Ctrl: 34.2+/-3.9 ml/kg/min vs NO3-: 31.7+/-4.4 ml/kg/min), submaximal exercise (average of min 25-45, Ctrl: 24.6+/-2.4 ml/kg/min vs NO3-: 26.8+/-3.3 ml/kg/min) or EPOC (area under the curve, Ctrl: 0.57+/-0.24 L vs NO3-: 0.66+/ 0.16 L). Thus, while NO3- supplementation may have performance benefits in elite athletes exercising at high intensities, in recreationally active males, there appears to be little impact on changes in VO2 due to maximal or submaximal prolonged exercise. PMID- 29795729 TI - Comparison of a Pneumatic Compression Device to a Compression Garment During Recovery from DOMS. AB - The purpose of this study was to determine the effects of a pneumatic compression device (PCD) compared to a continuously-worn compression sleeve (CS) during a five-day recovery period from delayed-onset muscle soreness (DOMS) of the elbow flexors. Eight college-aged students participated in this crossover design study. The muscle-damage protocol consisted of four sets of 25 repetitions of isokinetic concentric elbow flexion followed by eccentric elbow extension at 60 degrees /second. Immediately following the muscle-damage protocol, subjects either wore a CS continually for five days or completed daily, 20-minute PCD treatments for five days. Swelling, range of motion (ROM), and pain were measured daily during the five-day recovery period. Subjects rested for seven additional days before completing another muscle-damage protocol and the remaining treatment. Treatment order was randomized and balanced. Muscle swelling, assessed via changes in upper arm circumference, was significantly lower in the PCD treatment (1.7 vs. 2.0 cm in CS, p = 0.012), however there was no difference in lower arm circumference (p = 0.091). ROM disturbances during the PCD treatment were lower (mean peak reduction in ROM -9.04 degrees in PCD compared to -17.25 degrees in CS, p < 0.05) and peak pain was lower by 39% (27.5 mm in PCD compared to 45.2 mm in CS, p < 0.05) when compared to the CS treatment. These findings suggest that daily treatments using a PCD further reduce peak disturbance and recovery time from DOMS of the elbow flexors when compared to a continuously-worn CS. PMID- 29795730 TI - No Effect of Assisted Hip Rotation on Bat Velocity. AB - Softball and baseball are games that require multiple skill sets such as throwing, hitting and fielding. Players spend a copious amount of time in batting practice in order to be successful hitters. Variables commonly associated with successful hitting include bat velocity and torso rotation. The concept of overspeed bodyweight assistance (BWA) has shown increases in vertical jump and sprint times, but not hip rotation and batting. The purpose of this study was to examine the effects of assisted hip rotation on bat velocity. Twenty-one male and female recreational softball and baseball players (15 males, age 23.8 +/- 3.1yrs; height 177.67 +/- 6.71cm; body mass 85.38 +/- 14.83kg; 6 females, age 21.5 +/- 2.1yrs; height 162.20 +/- 9.82cm; body mass 60.28 +/- 9.72kg) volunteered to participate. Four different BWA conditions (0%, 10%, 20%, and 30%) were randomly applied and their effects on bat velocity were analyzed. Subjects performed three maximal effort swings under each condition in a custom measurement device and average bat velocity (MPH) was used for analysis. A mixed factor ANOVA revealed no interaction (p=0.841) or main effect for condition, but there was a main effect for sex where males had greater bat velocity (43.82+/-4.40 - 0% BWA, 41.52+/-6.09 - 10% BWA, 42.59+/-7.24 - 20% BWA, 42.69+/-6.42 - 30% BWA) than females (32.57+/-5.33 - 0% BWA, 31.69+/-3.40 - 10% BWA, 32.43+/-5.06 - 20% BWA, 32.08+/-4.83 - 30% BWA) across all conditions Using the concept of overspeed training with assisted hip rotation up to 30% BWA did not result in an increase in bat velocity. Future research should examine elastic band angle and hip translation at set-up. PMID- 29795731 TI - Influence of Baseline Muscle Strength and Size Measures on Training Adaptations in Resistance-trained Men. AB - The influence of baseline strength or muscle size on adaptations to training is not well-understood. Comparisons between novice and advanced lifters, and between stronger and weaker experienced-lifters, have produced conflicting results. This study examined the effect of baseline muscle strength and size on subsequent adaptations in resistance-trained individuals following a traditional high volume, short-rest resistance training protocol. Fourteen resistance-trained men (24.0+/-2.7 y; 90.1+/-11.7 kg; 169.9+/-29.0 cm) completed pre-training (PRE) ultrasound measurements of muscle cross-sectional area (CSA) in the rectus femoris (RF), vastus lateralis (VL), pectoralis major, and triceps brachii (TRI) prior to strength assessments (e.g., one-repetition maximum strength bench press and back-squat). Post-training (POST) assessments were completed following 8-wks (4 d.wk-1) of resistance training. Comparisons were made between stronger (STR) and weaker (WKR) participants, and between larger (LGR) and smaller (SMR) participants, based upon PRE-muscle strength and size, respectively. When groups were based on upper-body strength, repeated measures analysis of variance indicated a significant group * time interaction where greater improvements in bench press strength were observed in WKR (12.5+/-8.6%, p = 0.013) compared to STR (1.3+/-5.4%, p=0.546). Within this comparison, STR also possessed more resistance training experience than WKR (mean difference=3.1 y, p=0.002). No other differences in experience or adaptations to training were observed. These data suggest that following a short-duration training program (8-weeks), baseline size and strength have little impact on performance gains in resistance-trained individuals who possess similar years of experience. However, when training experience is different, baseline strength may affect adaptations. PMID- 29795732 TI - Acute Specific Effects of Caffeine-containing Energy Drink on Different Physical Performances in Resistance-trained Men. AB - Caffeine containing energy drink (ED) is frequently used as ergogenic aid, but its effect on performance need more investigation. Thus, the aim of this study was to analyze the effects of acute ingestion of an ED on the physical performance of resistance-trained men subjected to successive tests in the same experimental protocol. Fifteen resistance-trained males (21.0 +/- 0.3 yrs; 177.4 +/- 1.8 cm; 79.6 +/- 1.8 kg) ingested 2.5 mg caffeine per kg of body weight (619.5 +/- 14.6 mL of ED) or a placebo in a double-blind randomized cross-over design. Physical performance was randomized for the maximum repetition tests (80% 1RM) in the bench press exercise and unilateral knee extension (dominant leg), maximal isometric hand-grip test in both hands, standing long jump and repeated sprint ability test. The paired Student-t test showed that ED intake increased performance compared to the placebo for the number of repetitions in the unilateral knee extension test of the dominant leg (11.5 +/- 0.9 reps vs 9.5 +/- 0.8 reps; P = 0.001) and bench press (10.2 +/- 0.4 reps vs 8.1 +/- 0.5 reps; P = 0.01); and also increased isometric strength in the hand-grip maximal test in the right (53.7 +/- 1.5 kg vs. 47.7 +/- 1.6 kg; P = 0.02) and left hand (52.9 +/- 1.5 kg vs. 45.9 +/- 1.3 kg; P = 0.02). In conclusion, acute ingestion of ED increased performance only in specific strength tests in resistance-trained men. PMID- 29795733 TI - Comparison of Body Composition Measurements in Lean Female Athletes. AB - This study compared body composition measurements in lean female athletes. The primary objective was to compare the accuracy of percent body fat (%BF) determined by bioelectrical impedance analysis (BIA), air-displacement plethysmography (ADP), and underwater weighing (UWW) in female Division I cheerleaders (n = 10 bases, 6 back-spots, and 12 flyers) from two universities. The secondary objective was to compare health risk predicted by %BF to body mass index (BMI) categorizations. UWW was considered the gold standard for assessing %BF. Pearson correlation coefficients were used to determine associations between methods. Repeated measures analysis of variance was used to identify differences in %BF by method. BIA, ADP, and UWW were highly correlated (r >= .828, p < .001 for all). However, %BF by BIA (20.0 +/- 5.2%) and ADP (19.3 +/- 6.0%) was higher than %BF by UWW (15.9 +/- 4.1%, p < .001). Health risk was predicted less often when classified based on very lean (risky low) %BF levels by BIA and ADP than UWW (7.1%, 3.6%, and 21.4%, respectively). This finding suggests that, similar to female track-and-field athletes who also exhibit lean muscular physiques, %BF is overestimated by BIA and ADP in female cheerleaders and health risk associated with low %BF is underestimated when compared to UWW. In contrast, BMI was not associated with %BF by any method and no participants were classified as underweight by this measure. Thus, BMI should not be used to predict health risk in lean female athletes, such as collegiate cheerleaders. PMID- 29795734 TI - Comparison of Techniques for Tracking Body Composition Changes across a Season in College Women Basketball Players. AB - Body composition assessment has become an integral part of athletes' training schedules. Questions remain concerning the accuracy of various methods to track body composition changes over a competitive year cycle. The purpose of this study was to compare various methods of tracking body composition across a college women's basketball season. Fourteen Division II women (age = 20.1 +/- 1.2 y) were measured prior to the season (T1), after pre-season conditioning (T2), at mid season (T3), and at the end of the season (T4) using skinfolds (SKF), two bioelectric impedance analysis (BIA) devices, and dual-energy x-ray absorptiometry (DXA). BIA devices were hand-to-hand (H-BIA) and foot-to-foot (F BIA) single-frequency models. SKF were used to estimate %fat using four prediction equations. A method * trial factorial ANOVA on %fat with repeated measures over the second factor indicated that all methods except the Durnin Womersley SKF equation were significantly lower than DXA. Across trials, DXA %fat at T1 (25.3 +/- 4.7%) was significantly higher than at T2 (24.3 +/- 4.6%), T3 (24.6 +/- 4.6%), and T4 (24.4 +/- 5.1%). Agreement between DXA and the other methods were moderate (r = 0.48 - 0.86). Rank-order correlations of DXA with the other methods to compare team order indicated H-BIA (rho = 0.67 - 0.78) and F-BIA (rho = 0.62 - 0.77) provided comparable agreement, with SKF methods having lower agreement for team order (rho = 0.46 - 0.73). Compared to the DXA standard, a foot-to-foot BIA device may provide adequate but significantly lower relative tracking of %fat across a women's basketball season. PMID- 29795735 TI - Discrimination against Obese Exercise Clients: An Experimental Study of Personal Trainers. AB - The aim of the study was to compare exercise recommendations, attitudes, and behaviors of personal trainers toward clients of different weight statuses. Fifty two personal trainers participated in the study. The data collection was organized into two phases. In phase one, trainers read a profile and watched the video displaying an interview of either an obese or an average-weight client. Profiles and video interviews were identical except for weight status. Then, trainers provided exercise recommendations and rated their attitude toward the client. In phase two, trainers personally met an obese or an average-weight mock client. Measures were duration and number of advices provided by the trainer to a question posed by the client and sitting distance between trainer and client. There were no significant differences in exercise intensity (p = .94), duration of first session (p = .65), and total exercise duration of first week (p = .76) prescribed to the obese and average-weight clients. The attitude of the personal trainers toward the obese client were not significantly different from the attitude of personal trainers toward the average-weight client (p = .58). The number of advices provided (p = .49), the duration of the answer (p = .55), and the distance personal trainers sat from the obese client (p = .68) were not significantly different from the behaviors displayed toward the average-weight client. Personal trainers did not discriminate against obese clients in professional settings. PMID- 29795737 TI - Practices, Perceived Benefits, and Barriers to Resistance Training Among Women Enrolled in College. AB - The American College of Sports Medicine (ACSM) has recommended that resistance training be performed at least twice per week, with 8-12 repetitions of 8-10 exercises targeting all major muscle groups (1). However, Kruger, Carlson, and Kohl (18) reported that women were participating less than the U.S. population on the whole, as only 20% of women were engaging in resistance training two or more times per week. In order to better understand why only 1 in 5 women participate regularly in this form of physical activity, this study investigated current resistance training practices, perceived benefits, and barriers to resistance training among college women. One-hundred and sixteen women college students from a large, public, Midwestern university participated in this study. Correlation and hierarchical multiple regression analyses were used to identify the strongest predictors of resistance training behaviors. The predictors in the regression model included demographic characteristics in block one, perceived barriers to resistance training in block two, and perceived benefits of resistance training in block three. Results indicated that the level of perceived "time/effort" barriers significantly predicted resistance training behavior. Findings in this area may help researchers, university recreation programmers, personal trainers, and other health and fitness professionals better understand the attitudes and actions of college women regarding resistance training, toward the goal of promoting fitness center environments that college women find more inviting. PMID- 29795736 TI - Determinants of Attendance at a Physical Activity Focused Afterschool Program in Elementary School Children. AB - Afterschool youth physical activity (PA) programs provide opportunities for increasing children's time engaged in moderate-to-vigorous physical activity (MVPA). However, low program attendance reduces the benefits of participating in these programs. The purpose of this study was to determine if enjoyment, athletic competence and motivation for PA predict youth attendance at a free afterschool PA program from 3rd to 5th grade. Data were collected from a larger randomized community trial examining the effectiveness of an afterschool program for increasing opportunities to engage in MVPA. Data were collected twice annually (fall/spring) over 3 school years (3rd - 5th grade) in 9 schools. Analyses were stratified by grade and sex, and a series of multi-level linear regression models were utilized to determine if baseline levels of the psychosocial determinants predicted annual attendance as a percentage of afterschool sessions attended. Amotivation for PA was negatively associated with attendance in boys and non-self determined extrinsic motivation was positively associated with attendance in girls in the 5th grade. Age was associated with a 13.72% reduction in attendance in the 3rd grade, a 12.87% attendance reduction in the 4th grade, and a 7.93% attendance in reduction in the 5th grade. Race was also associated with attendance. Non-White youth attended the program 13.56% less in the 3rd grade, 17.35% less in the 4th grade, and 21.53% less in the 5th grade than White youth. The findings suggest that attendance to PA afterschool programming may be associated with children's motivational characteristics, but that other variables should be identified for further research. PMID- 29795739 TI - External Feedback Does Not Affect Running Pace in Recreational Runners. AB - Many runners receive external feedback, such as running pace, during training; however, it is unknown if this feedback increases the intensity of a given exercise session. Therefore, the purpose of this study was to examine the effect of the provision of pace feedback on self-selected submaximal running pace, heart rate, and perceived exertion in recreational runners. Ten runners (6 female, 4 male) completed four 30-min treadmill running bouts in random order, each on a separate day. In each session, participants adjusted their pace as desired; however, all treadmill display information was concealed from the runners. During each bout, participants were given feedback regarding running pace every five minutes as follows: 1) no pace feedback, 2) accurate pace feedback 3) false positive pace feedback (5% faster than the actual pace), or 4) false negative pace feedback (5% slower than the actual pace). Average running paces were 5:35 +/- :12, 5:32 +/- :12, 5:30 +/- :12, and 5:30 +/- :12 min:sec/km for the no pace, accurate pace, false positive, and false negative feedback conditions, respectively, which were not statistically different. The different feedback conditions also yielded no significant differences in average heart rate, maximal heart rate, or rating of perceived exertion. These results suggest that periodic external feedback regarding running pace does not affect overall self-selected running pace or exercise intensity during a running bout in recreational runners. PMID- 29795738 TI - A Cross-Training Program Does Not Alter Self-Reported Physical Activity Levels in Elementary School Children. AB - The purpose of the study was to examine the effects of a school-based cross training program on body mass index (BMI), attitudes toward physical activity (ATPA), and physical activity (PA) levels of children in the 4th and 5th grades. Children (N = 118) were divided into control (n = 60) and experimental (n = 58) groups based on class availability. While the control group continued academic classes as usual, the experimental group participated in cross-training involving resistance training (RT), calisthenics, and stretching twice a week for 10 weeks. Pre- and post-intervention measures included height, mass, ATPA, and PA. BMI was calculated and ATPA and PA levels were assessed via questionnaire. The groups did not differ significantly (p > .05) for either pre- or post-intervention regarding BMI, ATPA, and PA. However, BMI and PA levels significantly increased over time for both groups (p <= .05). Overall, cross-training in a school setting may be a safe and enjoyable option for physical activity participation. BMI and PA increases were likely the result of the natural growth process and seasonal weather pattern changes, respectively. Nevertheless, the cross-training did not detract from PA levels and may have led to an overall increase in PA levels. As subdomain analyses revealed decreased attitude toward health and fitness in the experimental group, shorter programs involving RT with various protocols are recommended. PMID- 29795740 TI - Effects of Starting Stance on Base Running Sprint Speed in Softball Players. AB - Speed is a crucial aspect in softball, and can be the difference between winning and losing. Base stealing is a method used to produce runs. There has been debate over which starting position is the most advantageous to maximize acceleration and speed to reach the next base the fastest. The purpose of this study was to examine the effect of different starting stances on acceleration and speed phases in collegiate softball players. Seventeen healthy NCAA Division I women's softball players (age = 19.9 +/- 1.3yrs, height = 167.0 +/- 5.4cm, mass = 74.8 +/ 14.1kg) volunteered to participate. Three maximum 45 ft sprints, with one minute rest, were performed (with splits at 15, 30 and 45ft) for each of three starting stances (front foot on the base, back foot on the base, and cross over stance). A 1*3 repeated measures ANOVA for total time demonstrated that front foot on the base was significantly faster (2.51 +/- 0.18s) than back foot on the base (2.70 +/- 0.19s) and the cross over step (2.66 +/- 0.23s). For all three splits, front foot on the base was also significantly faster (0.96 +/- 0.07s, 0.81 +/- 0.06s, and 0.73 +/- 0.06s) than back foot on the base (1.10 +/- 0.13s, 0.84 +/- 0.05s, and 0.75 +/- 0.43s) and cross over step (1.04 +/- 0.09s, 0.84 +/- 0.06s, and 0.75 +/- 0.07s). The decrease in time for front foot on the base was probably the result of using the base to push against, like a sprinter's block, to produce greater horizontal force to accelerate faster and reach a greater top speed. Coaches should teach their softball athletes to stand with their front foot on the base when base running. PMID- 29795741 TI - Simulated Altitude via Re-Breathing Creates Arterial Hypoxemia but Fails to Improve Elements of Running Performance. AB - Acclimatization to altitude has been shown to improve elements of performance. Use of simulated altitude is popular among athletes across the sports spectrum. This work was on a handheld, re-breathing device touted to enhance performance. Seven recreationally-trained athletes used the device for 18 hours over the course of the 37-day intervention trial. The elevations simulated were progressively increased from 1,524m to 6,096m. To ascertain potential efficacy, four performance trials were included (familiarization, baseline, and 2 follow ups). Hematological (hematocrit, hemoglobin, and lactate), physiological (respiratory exchange ratio, heart rate, and oxygen consumption), and perceptual (Borg's RPE) variables were monitored at rest, during two steady state running economy stages, and at maximal effort during each visit. The device is clearly capable of creating arterial hypoxemic conditions equating to high altitude. This fact is exemplified by average pulse oximetry values of approximately 78.5% in the final 6-day block of simulation. At the same time, there were no changes observed in any hematological (p>0.05), physiological (p>0.05), or perceptual (p>0.05) variable at either follow-up performance trial. Relative VO2 data was analyzed with a 15-breath moving average sampling frequency in accordance with our recent findings (Scheadler et al.) reported in Medicine and Science in Sports and Exercise. Effect sizes are reported within, but most were trivial (d=0.0 0.19). Overall, findings align with speculation that a more robust altitude stimulus than can be offered by short-term arterial hypoxemia is required for changes to be evidenced. The device has shown some promise in other work, but our data is not supportive. PMID- 29795742 TI - Sex and Age Differences in Trail Half Marathon Running. AB - Female participation is growing in trail running races. The purpose was to evaluate sex and age differences in top finishers of a trail running half marathon. Velocity differences between males (M) and females (F) were determined for the top 10 finishers of the Moab Trail Half Marathon from 2012 - 2015 across age, and by finishing place. Differences between age category and between sexes were determined through ANOVA with significance accepted at P < 0.05. A significant difference for running velocity was present between sexes at each age category (20-29 yr F = 2.9+/-0.3, M = 3.4+/-0.4 m.sec-1; 30-39 yr F = 2.8+/-0.3, M = 3.3+/-0.3; 40-49 yr F = 2.7+/-0.3, M = 3.0+/-0.5; 50-59 yr F = 2.3+/-0.2, M = 2.8+/-0.3; 60-69 yr F = 1.6+/-0.3, M = 2.2+/-0.4; P < 0.0001). Sex difference in trail running velocity was consistent (~13%) among all age categories with exception of the oldest group (33%, P = 0.0001). There were significantly greater female finishers in every age category (20 - 29 yr F = 107+/-18, M = 56+/-1;, 30 39 yr F = 150+/-34, M = 84+/-21; 40 - 49 yr F = 112+/-17, M = 64+/-16; P < 0.01) until 50 - 59 yr (F = 48+/-13, M = 41+/-14; P = 0.50). These data indicate that the widening gap in sex differences observed in road races are ameliorated in a trail running environment that has a larger number of female participants. PMID- 29795743 TI - Rate of Performance Change in American Female Weightlifters Over Ten Years of Competition. AB - The purpose of this study was to evaluate the rates of performance change for American female weightlifters over 10 years of competition. Athlete performance results were gathered from the United States Weightlifting open access, results archive, database. Data was delimited to athletes (N >= 750) that competed in Youth or Junior Nationals to ensure athletes were <21yrs old at the first recorded competition. Competition results were converted to strength to mass (SM) ratios to control for the effect of bodyweight on performance. Starting with the first competition date, the highest SM for the snatch (SNT), clean and jerk (CJ) and combined total (T), in three month segments for three years, and six month segments over 10 years, were recorded. Observed percentage change in SM and Cohen's d effect size (ES) between each 3-and 6-month segment and the first competition (baseline), for the SNT, CJ and T, was determined. Positive change in rate of performance peaked between time segments baseline-6mo and 7mo-12mo for the SNT (+8.7%, SM 0.68+/-0.19 to 0.74+/-0.19, ES=0.34), CJ (+7.7%, SM 0.90+/ 0.24 to 0.97+/-0.24, ES=0.31) and T (+8.2%, SM 1.57+/-0.41 to 1.71+/-0.42 ES=0.34). Total performance increase over 10yrs for the SNT was 27.7% (Year 1 SM 0.68+/-0.18, year 10 SM 1.13+/-0.24, ES=0.96), the CJ 22.2% (Year 1 SM 0.90+/ 0.23, year 10 SM 1.40+/-0.30, ES=0.84), and T 25.0% (Year 1 SM 1.56+/-0.41, year 10 SM 2.53+/-0.53, ES=0.91). Observed rates in performance change could be useful for weightlifting coaches as a barometer for evaluating training program outcomes over time. PMID- 29795744 TI - Does Body Mass Index Influence the Physiological and Perceptual Demands Associated with Defensive Tactics Training in State Patrol Officers? AB - The purpose of this investigation was to determine the physiological and perceptual demands associated with defensive tactics (DEFTAC) training among state patrol officers of different BMI (body mass index) categories. Twenty-four male state patrol officers (n = 24, age 36.00 + 7.86 yrs) voluntarily agreed to participate in data collection during a DEFTAC gauntlet. Anthropometric information (height (HT) 182.19 + 7.43 cm and weight (WT) 96.31 + 17.45 kg), body mass index (BMI), peak and average heart rates, duty weight, BLa, and RPE, were recorded. Officers were then divided into two-groups (Healthy BMI (BMI <= 25), n = 12, Overweight (BMI >= 25), n = 12). Analyses of covariance (ANCOVAs) were conducted to determine the effect of BMI on the outcome variables. Furthermore, a Pearson's product-moment correlation coefficient was also conducted to determine if significant relationships between RPE, BLa, and HR existed between groups. Significant mean score differences between healthy and overweight officers were found in measures of age [t(22) 4.12, p< 0.01, R2 = .44], and weight of duty gear [t(21) 3.96, p<0.01, R2 = .33]. When used as a covariate, age also predicted average HR% [ F(1, 21) = 6.19, p < .05, partial eta2 = .24]. Significant relationships were found in the healthy group between RPE and DEFTAC time, DEFTAC time and score, as well as score and post BLa. Significant relationships for the overweight group between peak (HR) percentage and post BLa, peak (HR) percentage and RPE, DEFTAC time and duty weight, and between weight and DEFTAC time. The results of this study suggest that overweight officers may have lower DEFTAC scores when compared to their healthy counterparts. Based on the results, it seems reasonable to compare physiological variables from this population to those from combative sports as well as for officers to achieve and maintain a healthy BMI value in order to improve individual DEFTAC performance. PMID- 29795745 TI - No Observable Relative Age Effects in Professional Surfers: a Constraints-Based Evaluation. AB - With the recent inclusion of surfing in the 2020 Olympic Games in Japan, there will be a number of surfing athletes vying for one of the twenty total available spots for their respective gender. The purpose was to evaluate relative age effects (RAEs) in surfing with consideration for specific developmental constraints. Elite competitive male surfers (n = 1590) were examined by birth month and subcategorized by competitive level, age groups, and geographical regions. The observed quarterly distribution was not significantly different (using chi2; p>0.05) from expected for the overall group or any of the subcategories. However, an odds ratio of 1.85 (90% confidence interval: 1.08 3.14) was calculated for being born in the first semester of the year compared to being born in the second semester between top 34 athletes and the rest of the field. Despite consideration for individual, environmental, and task constraints in this study, the sport of surfing does not appear to have any observable RAEs at the professional level. Thus, surfing appears to be one of the few sporting activities included in the Olympic Programme with limited RAEs. PMID- 29795746 TI - Global Active Stretching (SGA(r)) Practice for Judo Practitioners' Physical Performance Enhancement. AB - In order to analyze the Global Active Stretching (SGA(r)) practice on the physical performance enhancement in judo-practitioner competitors, 12 male athletes from Judo Federation of Sergipe (Federacao Sergipana de Judo), were divided into two groups: Experimental Group (EG) and Control Group (CG). For 10 weeks, the EG practiced SGA(r) self-postures and the CG practiced assorted calisthenic exercises. All of them were submitted to a variety of tests (before and after): handgrip strength, flexibility, upper limbs' muscle power, isometric pull-up force, lower limbs' muscle power (squat-jump - SJ and countermovement jump - CMJ) and Tokui Waza test. Due to the small number of people in the sample, the data were considered non-parametric and then we applied the Wilcoxon test using the software R version 3.3.2 (R Development Core Team, Austria). The effect size was calculated and considered statistically significant the values p <= 0.05. Concerning the results, the EG statistical differences were highlighted in flexibility, upper limbs' muscle power and lower limbs' muscle power (CMJ), with a gain of 3.00 +/- (1.09) cm, 0,42 +/- (0,51) m and 2.49 +/- (0.63) cm, respectively. The CG only presented statistical difference in the lower limbs' test (CMJ), with a gain of 0,55 +/- 2,28 cm. Thus, the main results pointed out statistical differences before and after in the EG in the flexibility, upper limbs and lower limbs' muscle power (CMJ), with a gain of 3.00 +/- 1.09 cm, 0.42 +/- 0.51 m 2.49 +/- 0.63 cm, respectively. On the other hand, the CG presented a statistical difference only the lower limbs' CMJ test, with a gain of 0.55 +/- 2.28 cm. The regular 10-week practice of SGA(r) self-postures increased judoka practitioners' posterior chain flexibility and vertical jumping (CMJ) performance. PMID- 29795747 TI - Allosteric Modulation of Ionotropic Glutamate Receptors Special Issue. AB - Call for papers! ACS Medicinal Chemistry Letters is now accepting manuscript submissions for a special issue entitled "Allosteric Modulation of Ionotropic Glutamate Receptors". This special issue is a cross-thematic issue with Journal of Medicinal Chemistry and ACS Chemical Neuroscience. The ACS Medicinal Chemistry Letters special issue is scheduled for publication in early 2019. PMID- 29795748 TI - 2,7-Diazaspiro[4,4]nonanes for the Treatment or Prevention of Cancers and Diabetes. PMID- 29795749 TI - Academic Drug Development: The DRIVE Model. AB - Although there are hundreds of academic drug discovery centers open around the world, there are comparatively few academic drug development centers that contain the key core competencies needed to progress a lead compound into clinical trials. This is largely a consequence of operating in the "Valley of Death" (i.e., insufficient infrastructure, expertise, and funding). We have created an academic drug development center called DRIVE (Drug Innovation Ventures at Emory) that was designed to overcome many of the intrinsic and occasionally unintended barriers associated with academic drug development. Herein, we report a proof of concept that the DRIVE model provides a robust framework for pursuing university based drug development, especially when the drugs in question target rare and neglected diseases. PMID- 29795750 TI - What Do You Get from DNA-Encoded Libraries? AB - Use of DNA-encoded libraries (DELs) in the pharmaceutical industry has rapidly increased. We discuss what to expect when you run a DEL screen and contemplate guidelines for library design. Additionally, we consider some visionary work and extrapolate to the future. PMID- 29795751 TI - Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation. AB - Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clinical trials. As a result, anticocaine vaccines must be further optimized to achieve clinical translation. Herein, we report a study on the relationship between vaccine efficacy and hapten stability toward hydrolysis. Two haptens developed by our laboratory, GND and GNE, were conjugated to tetanus toxoid (TT) and formulated with alum and cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) adjuvants, the optimal formulation in anticocaine vaccine design. GND, a diamide, is more hydrolytically stable than GNE, a monoamide, toward butyrylcholinesterases. Ultimately, both vaccines induced antibodies with high affinity for cocaine. In hyperlocomotion testing, GND-TT and GNE-TT vaccinated mice exhibited a robust blockade of cocaine's stimulatory effects at all tested doses. Overall, antibodies raised against both haptens were highly effective in protecting mice from cocaine-induced psychostimulation. PMID- 29795752 TI - Aminoisoxazoles as Potent Inhibitors of Tryptophan 2,3-Dioxygenase 2 (TDO2). AB - Tryptophan 2,3-dioxygenase 2 (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers; therefore, TDO inhibition may be a useful therapeutic intervention for cancers. We identified an aminoisoxazole series as potent TDO2 inhibitors from a high-throughput screen (HTS). An extensive medicinal chemistry effort revealed that both the amino group and the isoxazole moiety are important for TDO2 inhibitory activity. Computational modeling yielded a binding hypothesis and provided insight into the observed structure-activity relationships. The optimized compound 21 is a potent TDO2 inhibitor with modest selectivity over indolamine 2,3-dioxygenase 1 (IDO1) and with improved human whole blood stability. PMID- 29795753 TI - SAR Studies of N-[2-(1H-Tetrazol-5-yl)phenyl]benzamide Derivatives as Potent G Protein-Coupled Receptor-35 Agonists. AB - G protein-coupled receptor-35 (GPR35) has emerged as a potential target in the treatment of pain and inflammatory and metabolic diseases. We have discovered a series of potent GPR35 agonists based on a coumarin scaffold and found that the introduction of a 1H-tetrazol-5-yl group significantly increased their potency. We designed and synthesized a new series of N-[2-(1H-tetrazol-5 yl)phenyl]benzamide derivatives through a two-step synthetic approach, and characterized their agonistic activities against GPR35 using a dynamic mass redistribution (DMR) assay. N-(5-bromo-2-(1H-tetrazol-5-yl)phenyl)-4 methoxybenzamide (56) and N-(5-bromo-2-(1H-tetrazol-5-yl)phenyl)-2-fluoro-4 methoxybenzamide (63) displayed the highest agonistic potency agonist GPR35 with an EC50 of 0.059 MUM and 0.041 MUM, respectively. The physicochemical properties of selected compounds were calculated to evaluate their druglikeness, suggesting that compounds 56 and 63 have good druglike properties. Together, N-[2-(1H tetrazol-5-yl)phenyl]benzamide derivatives are potentially great candidates for developing potent GPR35 agonists. PMID- 29795754 TI - Phenotypic Screening To Discover Novel Chemical Series as Efficient Antihemorrhagic Agents. AB - In an effort to find novel chemical series as antifibrinolytic agents, we explore alpha-phenylsulfonyl-alpha-spiropiperidines bearing different zinc-binding groups (ZBGs) to target those metalloproteinases involved in the fibrinolytic process: MMP3 and MMP10. Surprisingly, all these new chemical series were inactive against these metalloproteinases; however, several new molecules retained the antifibrinolytic activity in a phenotypic functional assay using thromboelastometry and human whole blood. Further optimization led to compound 38 as a potent antifibrinolytic agent in vivo, three times more efficacious than the current standard-of-care (tranexamic acid, TXA) at 300 times lower dose. Finally, in order to decipher the underlying mode-of-action leading to this phenotypic response, an affinity-based probe 39 was successfully designed to identify the target involved in this response: a potentially unknown mechanism-of-action in the fibrinolytic process. PMID- 29795755 TI - Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation. AB - Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions. PMID- 29795756 TI - Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1). AB - Sodium-phosphate cotransporter 2a, or NaPi2a (SLC34A1), is a solute-carrier (SLC) transporter located in the kidney proximal tubule that reabsorbs glomerular filtered phosphate. Inhibition of NaPi2a may enhance urinary phosphate excretion and correct maladaptive mineral and hormonal derangements associated with increased cardiovascular risk in chronic kidney disease-mineral and bone disorder (CKD-MBD). To date, only nonselective NaPi inhibitors have been described. Herein, we detail the discovery of the first series of selective NaPi2a inhibitors, resulting from optimization of a high-throughput screening hit. The oral PK profile of inhibitor PF-06869206 (6f) in rodents allows for the exploration of the pharmacology of selective NaPi2a inhibition. PMID- 29795757 TI - Discovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties. AB - A novel series of CXCR4 antagonists with piperidinyl and piperazinyl alkylamine side chains designed as butyl amine replacements are described. Several of these compounds showed similar activity to the parent compound TIQ-15 (5) in a SDF-1 induced calcium flux assay. Preliminary structure-activity relationship investigations led us to identify a series containing N-propyl piperazine side chain analogs exemplified by 16 with improved off-target effects as measured in a muscarinic acetylcholine receptor (mAChR) calcium flux assay and in a limited drug safety panel screen. Further efforts to explore SAR and optimize drug properties led to the identification of the N'-ethyl-N-propyl-piperazine tetrahydroisoquinoline derivative 44 and the N-propyl-piperazine benzimidazole compound 37, which gave the best overall profiles with no mAChR or CYP450 inhibition, good permeability in PAMPA assays, and metabolic stability in human liver microsomes. PMID- 29795758 TI - Radiosynthesis and Evaluation of [11C]HD-800, a High Affinity Brain Penetrant PET Tracer for Imaging Microtubules. AB - Microtubules (MTs) are highly abundant throughout the cytoskeleton, and their dysfunction is implicated in the pathogenesis of malignancies, various neurodegenerative disorders, and brain injuries. Validated radiotracers reported so far for MTs are [11C]paclitaxel, [18F]fluoropaclitaxel, and [11C]docetaxel; however, they are well-characterized substrates of efflux transporters and consequently have poor uptake into the brain due to minimal blood brain barrier (BBB) penetration. PET imaging of MT expression requires radiolabeled BBB penetrating MT ligands, and it may offer a direct and more sensitive approach for early diagnosis, monitoring disease progression, and treatment effects in brain diseases and assessing the clinical potential of targeted therapeutics and treatments. We have identified N-(4-methoxyphenyl)-N-5-dimethylfuro[2,3 d]pyrimidin-4-amine (HD-800) as a high affinity and selective colchicine site tubuline inhibitor amenable to radiolabel with C-11, a positron emitting isotope. HD-800 and desmethyl-HD-800 were synthesized in one step with 75% and 80% yields respectively from commercial synthons. The radiosynthesis of [11C]HD-800 was achieved in 45 +/- 5% yield at EOS. Ex vivo biodistribution binding data of [11C]HD-800 indicate that the radioligand penetrated the BBB and it was retained in brain with 75% specific binding. Apart from the brain, specific binding was observed in muscle (55%), heart (50%), lungs (43%), blood (37%), and pancreas (30%). MicroPET imaging in mice showed excellent binding in brain that was blocked by preadministration of unlabeled HD-800 and a colchicine site binding MT ligand MPC-6827. The above results indicate that [11C]HD-800 may be a suitable PET ligand for the in vivo quantification of MT inside and outside the brain. PMID- 29795759 TI - Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes. AB - The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy. PMID- 29795760 TI - Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology. AB - A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications. PMID- 29795761 TI - Heteronanoparticles by Self-Assembly of Ecdysteroid and Doxorubicin Conjugates To Overcome Cancer Resistance. AB - Heteronanoparticles (H-NPs) consisting of conjugates characterized by a squalene tail linked to doxorubicin and ecdysteroid derivatives are presented. Biological evaluation on A2780ADR cell line confirms not only the maintenance of the activity of the parental drug but also the ability to overcome cancer resistance. The in vitro cell uptake was demonstrated, and the involvement of an endosomal mediated pathway was suggested. PMID- 29795763 TI - Structure-Activity Relationships of Radioiodinated Benzoimidazopyridine Derivatives for Detection of Tau Pathology. AB - It is generally accepted that neurofibrillary tangles consisting of tau proteins are involved in the pathogenesis of Alzheimer's disease (AD). For selective detection of tau pathology, we synthesized and evaluated radioiodinated benzoimidazopyridine (BIP) derivatives with an alkylamino group as tau imaging probes. In vitro selectivity to tau aggregates and in vivo pharmacokinetics of BIP derivatives varied markedly, being strongly dependent on the alkylamino group. In in vitro autoradiography with AD brain sections, the BIP derivative with a dimethylamino group (BIP-NMe2) showed the highest selectivity to tau aggregates. Regarding the biodistribution using normal mice, the BIP derivative with an ethylamino group (BIP-NHEt) showed the highest uptake (6.04% ID/g at 2 min postinjection) into and rapid washout (0.12% ID/g at 60 min postinjection) from the brain. These results suggest that the introduction of an optimal alkylamino group into the BIP scaffold may lead to the development of more potential tau imaging probes. PMID- 29795762 TI - BMS-986163, a Negative Allosteric Modulator of GluN2B with Potential Utility in Major Depressive Disorder. AB - There is a significant unmet medical need for more efficacious and rapidly acting antidepressants. Toward this end, negative allosteric modulators of the N-methyl d-aspartate receptor subtype GluN2B have demonstrated encouraging therapeutic potential. We report herein the discovery and preclinical profile of a water soluble intravenous prodrug BMS-986163 (6) and its active parent molecule BMS 986169 (5), which demonstrated high binding affinity for the GluN2B allosteric site (Ki = 4.0 nM) and selective inhibition of GluN2B receptor function (IC50 = 24 nM) in cells. The conversion of prodrug 6 to parent 5 was rapid in vitro and in vivo across preclinical species. After intravenous administration, compounds 5 and 6 have exhibited robust levels of ex vivo GluN2B target engagement in rodents and antidepressant-like activity in mice. No significant off-target activity was observed for 5, 6, or the major circulating metabolites met-1 and met-2. The prodrug BMS-986163 (6) has demonstrated an acceptable safety and toxicology profile and was selected as a preclinical candidate for further evaluation in major depressive disorder. PMID- 29795764 TI - Discovery and Development of 8-Substituted Cycloberberine Derivatives as Novel Antibacterial Agents against MRSA. AB - 8-Acetoxycycloberberine (2) with a unique skeleton was first identified to display a potent activity profile against Gram-positive bacteria, especially methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration (MIC) values of 1-8 MUg/mL, suggesting a possible novel mechanism of action against bacteria. Taking 2 as the lead, 23 new 8-substituted cycloberberine (CBBR) derivatives including ether, amine, and amide were synthesized and evaluated for their antibacterial effect. The structure-activity relationship revealed that the introduction of a suitable substituent at the 8-position could greatly enhance the potency against MRSA. Among them, compounds 5d and 9e demonstrated equally effective anti-MRSA potency as lead 2, with an advantage of having a more stable pharmacokinetics feature. A preliminary mechanism study indicated that compound 9e acted upon bacteria partly through catalyzing the cleavage of bacterial DNA. Therefore, we consider that 8-substituted CBBR derivatives constitute a promising class of antibacterial agents in the treatment of MRSA infections. PMID- 29795765 TI - Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D. AB - Complement Factor D, a serine protease of the S1 family and key component of the alternative pathway amplification loop, represents a promising target for the treatment of several prevalent and rare diseases linked to the innate immune system. Previously reported FD inhibitors have been shown to bind to the FD active site in its self-inhibited conformation characterized by the presence of a salt bridge at the bottom of the S1 pocket between Asp189 and Arg218. We report herein a new set of small-molecule FD ligands that harbor a basic S1 binding moiety directly binding to the carboxylate of Asp189, thereby displacing the Asp189-Arg218 ionic interaction and significantly changing the conformation of the self-inhibitory loop. PMID- 29795766 TI - Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists. AB - Neuromedin U (NMU) is a multifunctional neuropeptide which is characterized by a high conservation through all species. Herein, we describe the synthesis of a novel set of NMU-analogs based on the truncated NMU-8. Through combination of previously reported modifications, an elaborate structure-activity relationship study was performed aiming for the development of peptides with an increased selectivity toward NMU receptor 1 (NMUR1). Compound 7 possessed the highest NMUR1 selectivity (IC50 = 0.54 nM, selectivity ratio = 5313) together with an increased potency (EC50 = 3.7 nM), an 18% increase of the maximal effect at NMUR1, and a higher resistance against enzymatic degradation as compared to the native NMU-8. The development of a potent NMUR1 agonist with extended half-life could represent an attractive tool to further unveil the role of NMUR1 in NMU signaling. PMID- 29795767 TI - Novel Nitric Oxide Donors of Phenylsulfonylfuroxan and 3-Benzyl Coumarin Derivatives as Potent Antitumor Agents. AB - In this work, five new hybrids of phenylsulfonylfuroxan merging 3-benzyl coumarin and their seco-B-ring derivatives 2-6 were designed and synthesized. Among them, compound 3 showed the most potent antiproliferation activities with IC50 values range from 0.5 to 143 nM against nine drug-sensitive and four drug-resistant cancer cell lines. Preliminary pharmacologic studies showed that these compounds displayed lower toxicities than that of lead compound 1. Compound 3 obviously induced the early apoptosis and hardly affected the cell cycle of A2780, which was significantly different from compound 1. Especially, it gave 559- and 294 fold selectivity antiproliferation activity in P-gp overexpressed drug-resistant cancer cell lines MCF-7/ADR and KB-V compared to their drug-sensitive ones MCF-7 and KB, implying that compounds 2-6 might have an extra mechanism of anti-MDR cancer with P-gp overexpression. PMID- 29795768 TI - Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction. AB - Telomeric repeat binding factor 2 (TRF2) is a telomere-associated protein that plays an important role in the formation of the 3' single strand DNA overhang and the "T loop", two structures critical for the stability of the telomeres. Apollo is a 5'-exonuclease recruited by TRF2 to the telomere and contributes to the formation of the 3' single strand DNA overhang. Knocking down of Apollo can induce DNA damage response similar to that caused by the knocking down of TRF2. In this Letter, we report the design and synthesis of a class of cyclic peptidic mimetics of the TRFH binding motif of Apollo (ApolloTBM). We found conformational control of the C terminal residues of ApolloTBM can effectively improve the binding affinity. We have obtained a crystal structure of a cyclic peptidic Apollo peptide mimetic (34) complexed with TRF2, which provides valuable guidance to the future design of TRF2 inhibitors. PMID- 29795769 TI - InDEx: Open Source iOS and Android Software for Self-Reporting and Monitoring of Alcohol Consumption. AB - InDEx is a software package for reporting and monitoring alcohol consumption via a smartphone application. Consumption of alcohol is self-reported by the user, and the app provides a visual representation of drinking behaviour and offers feedback on consumption levels compared to the general population. InDEx is intended as an exemplar app, operating as a standalone smartphone application and is highly customisable for a variety of research domains. InDEx is written in JavaScript, using IONIC framework which is cross-platform and is available under the liberal GNU General Public License (v3). The software is available from GitHub (https://github.com/DrDanL/index-app-public). PMID- 29795770 TI - PhytobezoarInduced Small Bowel Obstruction in a Young Male with Virgin Abdomen. AB - Phytobezoars are a rare cause of small bowel obstruction. Such cases are most commonly associated with previous abdominal surgery or poor dentition or psychiatric conditions. A 40 year old man with a virgin abdomen and excellent dentition and no underlying psychiatric condition presented with an acute abdomen. CT scan revealed a transition point between dilated proximal loops of small bowel and collapsed distal loops. Exploratory laparotomy revealed a phytobezoar unable to be milked into the cecum and an enterectomy with primary anastamosis was performed without complication. A detailed history revealing several less common predisposing factors for phytobezoars should increase clinical suspicion of a phytobezoarinduced small bowel obstruction in the setting of an acute abdomen. Vigilance in presentations of an acute abdomen improves the usefulness of medical imaging, such as a CT, to detect phytobezoars. Understanding mechanisms of phytobezoar formation helps guide management and may prevent surgery. PMID- 29795771 TI - Effectively Measuring Respiratory Flow With Portable Pressure Data Using Back Propagation Neural Network. AB - Continuous respiratory monitoring is an important tool for clinical monitoring. The most widely used flow measure device is nasal cannulae connected to a pressure transducer. However, most of these devices are not easy to carry and continue working in uncontrolled environments which is also a problem. For portable breathing equipment, due to the volume limit, the pressure signals acquired by using the airway tube may be too weak and contain some noise, leading to huge errors in respiratory flow measures. In this paper, a cost-effective portable pressure sensor-based respiratory measure device is designed. This device has a new airway tube design, which enables the pressure drop efficiently after the air flowing through the airway tube. Also, a new back propagation (BP) neural network-based algorithm is proposed to stabilize the device calibration and remove pressure signal noise. For improving the reliability and accuracy of proposed respiratory device, a through experimental evaluation and a case study of the proposed BP neural network algorithm have been carried out. The results show that giving proper parameters setting, the proposed BP neural network algorithm is capable of efficiently improving the reliability of newly designed respiratory device. PMID- 29795772 TI - Enabling Stroke Rehabilitation in Home and Community Settings: A Wearable Sensor Based Approach for Upper-Limb Motor Training. AB - High-dosage motor practice can significantly contribute to achieving functional recovery after a stroke. Performing rehabilitation exercises at home and using, or attempting to use, the stroke-affected upper limb during Activities of Daily Living (ADL) are effective ways to achieve high-dosage motor practice in stroke survivors. This paper presents a novel technological approach that enables 1) detecting goal-directed upper limb movements during the performance of ADL, so that timely feedback can be provided to encourage the use of the affected limb, and 2) assessing the quality of motor performance during in-home rehabilitation exercises so that appropriate feedback can be generated to promote high-quality exercise. The results herein presented show that it is possible to detect 1) goal directed movements during the performance of ADL with a [Formula: see text] statistic of 87.0% and 2) poorly performed movements in selected rehabilitation exercises with an [Formula: see text]-score of 84.3%, thus enabling the generation of appropriate feedback. In a survey to gather preliminary data concerning the clinical adequacy of the proposed approach, 91.7% of occupational therapists demonstrated willingness to use it in their practice, and 88.2% of stroke survivors indicated that they would use it if recommended by their therapist. PMID- 29795773 TI - Hepatic, Periportal, Retroperitoneal, and Mesenteric Neurofibromatosis in von Recklinghausen's Disease. AB - We present a rare case of histologically proven neurofibromatosis of the liver, hepatic hilum, retroperitoneum, and mesentery. An adult male who had been diagnosed with neurofibromatosis (NF) type 1 underwent a computed tomography (CT) scan for abdominal pain and vomiting. The CT scan showed a large low-attenuating lesion in the region of porta hepatis which was infiltrating along portal tracts into the liver, encasing the major vessels, and extending into the retroperitoneum and mesentery. Based on the radiological findings, a differential diagnosis of plexiform neurofibroma was given, although sarcomatous transformation could not have been entirely excluded from imaging alone. The tumor was subsequently biopsied, and the histopathological analysis confirmed the diagnosis of neurofibroma. This case highlights the importance and diagnostic dilemmas in the presence of this tumor at atypical locations in this disease spectrum. PMID- 29795774 TI - Role of Farnesoid X Receptor in the Determination of Liver Transcriptome during Postnatal Maturation in Mice. AB - The liver is a vital organ with critical functions in metabolism of various biologically useful materials, synthesis of several vital proteins, detoxification of toxic substances, and immune defense. Most liver functions are not mature at birth and many changes happen during postnatal liver development, which lead to differential vulnerabilities of the liver at different developmental stages. However, the details of what changes occur in liver after birth, at what developmental stages they occur, and molecular mechanisms in the regulation of the developmental process are not clearly known. The nuclear receptor Farnesoid X receptor (FXR) is an important transcriptional regulator in liver. Here, we used RNA-Sequencing to analyze the transcriptome of mouse liver from perinatal to adult ages in both C57BL/6 and Fxr-/- mice. We have defined a clear timeline of functional transition from prenatal through neonatal and adolescent to adult in C57BL/6 mice. Without FXR, activation of neonatal-specific pathways was prolonged and maturation of multiple metabolic pathways was delayed. The loss of FXR also led to increased expression of 27 other transcription regulators. Our data support a conclusion that developmental transcriptome revealed significant functional transition during postnatal liver development and FXR plays an important role in control of postnatal liver maturation. PMID- 29795775 TI - Using a simulation approach to optimize time-domain diffuse correlation spectroscopy measurement on human head. AB - Time-domain diffuse correlation spectroscopy (TD-DCS) has been recently proposed to improve detection of deep blood flow dynamics in a biological tissue, such as human brain. To obtain a high sensitive measurement, several experimental parameters such as the source-detector (SD) distance, gate opening time, and width need to be considered and optimized. We use a simulation approach to optimize these parameters based on Monte Carlo computations using a realistic human head model. Two cortical regions are investigated including the frontal and temporal lobes. SD distance ranging from 0 to 45 mm, gate opening time from 400 to 1000 ps, and gate width from 50 to 3000 ps are considered. The goal is to find out the optimal combinations of these parameters by which the higher contrast measurement on the cortical dynamics can be achieved. The simulations show that with an acceptable input power of light, the combinations of SD distance ranging from 0 to 15 mm, gate opening time at 700 to 800 ps, and gate width of 800 ps are optimal for achieving higher contrast measurement on the cortical dynamics. The simulation approach and results are helpful for the optimization of TD-DCS experimental design focused on brain functional detection. PMID- 29795776 TI - Paired split-plot designs of multireader multicase studies. AB - The widely used multireader multicase ROC study design for comparing imaging modalities is the fully crossed (FC) design: every reader reads every case of both modalities. We investigate paired split-plot (PSP) designs that may allow for reduced cost and increased flexibility compared with the FC design. In the PSP design, case images from two modalities are read by the same readers, thereby the readings are paired across modalities. However, within each modality, not every reader reads every case. Instead, both the readers and the cases are partitioned into a fixed number of groups and each group of readers reads its own group of cases-a split-plot design. Using a [Formula: see text]-statistic based variance analysis for AUC (i.e., area under the ROC curve), we show analytically that precision can be gained by the PSP design as compared with the FC design with the same number of readers and readings. Equivalently, we show that the PSP design can achieve the same statistical power as the FC design with a reduced number of readings. The trade-off for the increased precision in the PSP design is the cost of collecting a larger number of truth-verified patient cases than the FC design. This means that one can trade-off between different sources of cost and choose a least burdensome design. We provide a validation study to show the iMRMC software can be reliably used for analyzing data from both FC and PSP designs. Finally, we demonstrate the advantages of the PSP design with a reader study comparing full-field digital mammography with screen-film mammography. PMID- 29795778 TI - Sacral Spinal Cord Transection and Isolated Sacral Cord Preparation to Study Chronic Spinal Cord Injury in Adult Mice. AB - Spinal cord injury (SCI) is characterized by multiple sensory/motor impairments that arise from different underlying neural mechanisms. Linking specific sensory/motor impairments to neural mechanism is limited by a lack of direct experimental access to these neural circuits. Here, we describe an experimental model which addresses this shortcoming. We generated a mouse model of chronic spinal cord injury that reliably reproduces spasticity observed after SCI, while at the same time allows study of motor impairments in vivo and in an in vitro preparation of the spinal cord. The model allows for the combination of mouse genetics in in vitro and in vivo conditions with advanced imaging, behavioral analysis, and detailed electrophysiology, techniques which are not easily applied in conventional SCI models. PMID- 29795777 TI - Cognitive processing differences of experts and novices when correlating anatomy and cross-sectional imaging. AB - The ability to correlate anatomical knowledge and medical imaging is crucial to radiology and as such, should be a critical component of medical education. However, we are hindered in our ability to teach this skill because we know very little about what expert practice looks like, and even less about novices' understanding. Using a unique simulation tool, this research conducted cognitive clinical interviews with experts and novices to explore differences in how they engage in this correlation and the underlying cognitive processes involved in doing so. This research supported what has been known in the literature, that experts are significantly faster at making decisions on medical imaging than novices. It also offers insight into the spatial ability and reasoning that is involved in the correlation of anatomy to medical imaging. There are differences in the cognitive processing of experts and novices with respect to meaningful patterns, organized content knowledge, and the flexibility of retrieval. Presented are some novice-expert similarities and differences in image processing. This study investigated extremes, opening an opportunity to investigate the sequential knowledge acquisition from student to resident to expert, and where educators can help intervene in this learning process. PMID- 29795779 TI - Interplay of cation and anion redox in Li4Mn2O5 cathode material and prediction of improved Li4(Mn,M)2O5 electrodes for Li-ion batteries. AB - Significant research effort has focused on improving the specific energy of lithium-ion batteries for emerging applications, such as electric vehicles. Recently, a rock salt-type Li4Mn2O5 cathode material with a large discharge capacity (~350 mA.hour g-1) was discovered. However, a full structural model of Li4Mn2O5 and its corresponding phase transformations, as well as the atomistic origins of the high capacity, warrants further investigation. We use first principles density functional theory (DFT) calculations to investigate both the disordered rock salt-type Li4Mn2O5 structure and the ordered ground-state structure. The ionic ordering in the ground-state structure is determined via a DFT-based enumeration method. We use both the ordered and disordered structures to interrogate the delithiation process and find that it occurs via a three-step reaction pathway involving the complex interplay of cation and anion redox reactions: (i) an initial metal oxidation, Mn3+->Mn4+ (Li x Mn2O5, 4 > x > 2); (ii) followed by anion oxidation, O2-->O1- (2 > x > 1); and (iii) finally, further metal oxidation, Mn4+->Mn5+ (1 > x > 0). This final step is concomitant with the Mn migration from the original octahedral site to the adjacent tetrahedral site, introducing a kinetic barrier to reversible charge/discharge cycles. Armed with this knowledge of the charging process, we use high-throughput DFT calculations to study metal mixing in this compound, screening potential new materials for stability and kinetic reversibility. We predict that mixing with M = V and Cr in Li4(Mn,M)2O5 will produce new stable compounds with substantially improved electrochemical properties. PMID- 29795780 TI - Observation of the quantum valley Hall state in ballistic graphene superlattices. AB - In graphene superlattices, bulk topological currents can lead to long-range charge-neutral flow and nonlocal resistance near Dirac points. A ballistic version of these phenomena has never been explored. We report transport properties of ballistic graphene superlattices. This allows us to study and exploit giant nonlocal resistances with a large valley Hall angle without a magnetic field. In a low-temperature regime, a crossover occurs toward a new state of matter, referred to as a quantum valley Hall state (qVHS), which is an analog of the quantum Hall state without a magnetic field. Furthermore, a nonlocal resistance plateau, implying rigidity of the qVHS, emerges as a function of magnetic field, and this plateau collapses, which is considered a manifestation of valley/pseudospin magnetism. PMID- 29795781 TI - A new route to synthesize aryl acetates from carbonylation of aryl methyl ethers. AB - Ether bond activation is very interesting because the synthesis of many valuable compounds involves conversion of ethers. Moreover, C-O bond cleavage is also very important for the transformation of biomass, especially lignin, which abundantly contains ether bonds. Developing efficient methods to activate aromatic ether bonds has attracted much attention. However, this is a challenge because of the inertness of aryl ether bonds. We proposed a new route to activate aryl methyl ether bonds and synthesize aryl acetates by carbonylation of aryl methyl ethers. The reaction could proceed over RhCl3 in the presence of LiI and LiBF4, and moderate to high yields of aryl acetates could be obtained from transformation of various aryl methyl ethers with different substituents. It was found that LiBF4 could assist LiI to cleave aryl methyl ether bonds effectively. The reaction mechanism was proposed by a combination of experimental and theoretical studies. PMID- 29795782 TI - Interface reconstruction with emerging charge ordering in hexagonal manganite. AB - Multiferroic materials, which simultaneously have multiple orderings, hold promise for use in the next generation of memory devices. We report a novel self assembled MnO double layer forming at the interface between a multiferroic YMnO3 film and a c-Al2O3 substrate. The crystal structures and the valence states of this MnO double layer were studied by atomically resolved scanning transmission electron microscopy and spectroscopy, as well as density functional theory (DFT) calculations. A new type of charge ordering has been identified within this MnO layer, which also contributes to a polarization along the [001] direction. DFT calculations further establish the occurrence of multiple couplings between charge and lattice in this novel double layer, in addition to the polarization in nearby YMnO3 single layer. The interface reconstruction reported here creates a new playground for emergent physics, such as giant ferroelectricity and strong magnetoelectric coupling, in manganite systems. PMID- 29795784 TI - Gate-tuned quantum Hall states in Dirac semimetal (Cd1-x Zn x )3As2. AB - The recent discovery of topological Dirac semimetals (DSMs) has provoked intense curiosity not only regarding Weyl physics in solids but also about topological phase transitions originating from DSMs. One specific area of interest is controlling the dimensionality to realize two-dimensional quantum phases such as quantum Hall and quantum spin Hall states. For investigating these phases, the Fermi level is a key controlling parameter. From this perspective, we report the carrier density control of quantum Hall states realized in thin films of DSM Cd3As2. Chemical doping of Zn combined with electrostatic gating has enabled us to tune the carrier density both over a wide range and continuously, even across the charge neutrality point. Comprehensive analyses of gate-tuned quantum transport have revealed Landau-level formation from linearly dispersed sub-bands and its contribution to the quantum Hall states. Our findings also pave the way for investigating the low-energy physics near the Dirac points of DSMs. PMID- 29795785 TI - Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations. AB - RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulations with nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields. PMID- 29795783 TI - Orientation-independent room temperature optical 13C hyperpolarization in powdered diamond. AB - Dynamic nuclear polarization via contact with electronic spins has emerged as an attractive route to enhance the sensitivity of nuclear magnetic resonance beyond the traditional limits imposed by magnetic field strength and temperature. Among the various alternative implementations, the use of nitrogen vacancy (NV) centers in diamond-a paramagnetic point defect whose spin can be optically polarized at room temperature-has attracted widespread attention, but applications have been hampered by the need to align the NV axis with the external magnetic field. We overcome this hurdle through the combined use of continuous optical illumination and a microwave sweep over a broad frequency range. As a proof of principle, we demonstrate our approach using powdered diamond with which we attain bulk 13C spin polarization in excess of 0.25% under ambient conditions. Remarkably, our technique acts efficiently on diamond crystals of all orientations and polarizes nuclear spins with a sign that depends exclusively on the direction of the microwave sweep. Our work paves the way toward the use of hyperpolarized diamond particles as imaging contrast agents for biosensing and, ultimately, for the hyperpolarization of nuclear spins in arbitrary liquids brought in contact with their surface. PMID- 29795786 TI - Graphene biointerfaces for optical stimulation of cells. AB - Noninvasive stimulation of cells is crucial for the accurate examination and control of their function both at the cellular and the system levels. To address this need, we present a pioneering optical stimulation platform that does not require genetic modification of cells but instead capitalizes on unique optoelectronic properties of graphene, including its ability to efficiently convert light into electricity. We report the first studies of optical stimulation of cardiomyocytes via graphene-based biointerfaces (G-biointerfaces) in substrate-based and dispersible configurations. The efficiency of stimulation via G-biointerfaces is independent of light wavelength but can be tuned by changing the light intensity. We demonstrate that an all-optical evaluation of use-dependent drug effects in vitro can be enabled using substrate-based G biointerfaces. Furthermore, using dispersible G-biointerfaces in vivo, we perform optical modulation of the heart activity in zebrafish embryos. Our discovery is expected to empower numerous fundamental and translational biomedical studies. PMID- 29795787 TI - Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer. AB - Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions. PMID- 29795789 TI - Associations Between the Length of Time from Transgender Identity Recognition to Hormone Initiation and Smoking Among Transgender Youth and Young Adults. AB - Purpose: Gender-affirming medical interventions have been associated with mental health improvements among transgender individuals. However, little is known about optimal timing of these interventions as they relate to stress-sensitive behaviors such as smoking. Methods: We analyzed electronic health record data from transgender youth and young adults to examine whether longer duration from transgender identity recognition to hormone initiation was associated with smoking behaviors. Results: Longer duration from age of identity recognition to age of cross-sex hormone initiation was associated with increased odds of current and lifetime smoking. Conclusion: Future research should investigate other potential risk factors associated with transgender-specific stressors for this population. PMID- 29795788 TI - Viromic Analysis of Wastewater Input to a River Catchment Reveals a Diverse Assemblage of RNA Viruses. AB - Detection of viruses in the environment is heavily dependent on PCR-based approaches that require reference sequences for primer design. While this strategy can accurately detect known viruses, it will not find novel genotypes or emerging and invasive viral species. In this study, we investigated the use of viromics, i.e., high-throughput sequencing of the biosphere's viral fraction, to detect human-/animal-pathogenic RNA viruses in the Conwy river catchment area in Wales, United Kingdom. Using a combination of filtering and nuclease treatment, we extracted the viral fraction from wastewater and estuarine river water and sediment, followed by high-throughput RNA sequencing (RNA-Seq) analysis on the Illumina HiSeq platform, for the discovery of RNA virus genomes. We found a higher richness of RNA viruses in wastewater samples than in river water and sediment, and we assembled a complete norovirus genotype GI.2 genome from wastewater effluent, which was not contemporaneously detected by conventional reverse transcription-quantitative PCR (qRT-PCR). The simultaneous presence of diverse rotavirus signatures in wastewater indicated the potential for zoonotic infections in the area and suggested runoff from pig farms as a possible origin of these viruses. Our results show that viromics can be an important tool in the discovery of pathogenic viruses in the environment and can be used to inform and optimize reference-based detection methods provided appropriate and rigorous controls are included. IMPORTANCE Enteric viruses cause gastrointestinal illness and are commonly transmitted through the fecal-oral route. When wastewater is released into river systems, these viruses can contaminate the environment. Our results show that we can use viromics to find the range of potentially pathogenic viruses that are present in the environment and identify prevalent genotypes. The ultimate goal is to trace the fate of these pathogenic viruses from origin to the point where they are a threat to human health, informing reference-based detection methods and water quality management. PMID- 29795791 TI - Impairment Severity and Evaluative and Experienced Well-being Among Older Adults: Assessing the Role of Daily Activities. AB - Background and Objectives: Physical impairments affect a substantial number of older adults in the United States, with rates increasing with advancing age. Impairment is linked with compromised well-being, although the reasons are not fully understood. We explore the extent to which linkages between impairment severity and well-being are accounted for by older adults' daily activities. We speculate that activities may influence global appraisals of well-being by offering the opportunity to fulfill productive and social roles and may influence daily emotions by shaping the context (places, people) in which life occurs. Research Design and Method: We examine the effects of impairment severity on life satisfaction and four diary-based experienced well-being measures (happiness, frustration, worry, and sadness). Data are from the Disability and Use of Time supplement to the Panel Study of Income Dynamics (n = 1,606), a national sample of adults ages 60 years and older in the United States. We estimate nested regression models, taking into account within-person correlations for experienced well-being. Results: Impairment severity is associated with poorer assessments of life satisfaction and all four dimensions of experienced well-being. Activity measures, which encompass eight productive (e.g., household chores) and three leisure (e.g., socializing) activities, account for 10% of the association between impairment and life satisfaction, and virtually none of the association between impairment and experienced well-being. However, psychosocial factors including higher neuroticism, lower self-efficacy, and poorer quality social relationships account for a sizeable share of the associations. Discussion and Implications: Role-fulfilling aspects of activities appear to be more central than contextual aspects of activities to the impairment-well-being relationship. However, potentially modifiable psychosocial factors account for a much greater share of this relationship. Further research is needed on whether interventions targeting these psychosocial factors might bolster emotional well-being for older adults experiencing impairments. PMID- 29795790 TI - Imbalance in Protein Thiol Redox Regulation and Cancer-Preventive Efficacy of Selenium. AB - Although several experimental studies showed cancer-preventive efficacy of supplemental dietary selenium, human clinical trials questioned this efficacy. Identifying its molecular targets and mechanism is important in understanding this discrepancy. Methylselenol, the active metabolite of selenium, reacts with lipid hydroperoxides bound to protein kinase C (PKC) and is oxidized to methylseleninic acid (MSA). This locally generated MSA selectively inactivates PKC by oxidizing its critical cysteine sulfhydryls. The peroxidatic redox cycle occurring in this process may explain how extremely low concentrations of selenium catalytically modify specific membrane-bound proteins compartmentally separated from glutathione and selectively induce cytotoxicity in promoting cells. Mammalian thioredoxin reductase (TR) is itself a selenoenzyme with a catalytic selenocysteine residue. Together with thioredoxin (Trx), it catalyzes reduction of selenite and selenocystine by NADPH generating selenide which in the presence of oxygen redox cycles producing reactive oxygen species. Trx binds with high affinity to PKC and reverses PKC inactivation. Therefore, established tumor cells overexpressing TR and Trx may escape the cancer-preventive actions of selenium. This suggests that in some cases, certain selenoproteins may counteract selenometabolite actions. Lower concentrations of selenium readily inactivate antiapoptotic PKC isoenzymes e and a which have a cluster of vicinal thiols, thereby inducing apoptosis. Higher concentrations of selenium also inactivate proapoptotic enzymes such as proteolytically activated PKCd fragment, holo-PKCz, caspase-3, and c-Jun N-terminal kinase, which all have a limited number of critical cysteine residues and make tumor cells resistant to selenium-induced apoptosis. This may explain the intriguing U-shaped curve that is seen with dietary selenium intake and the extent of cancer prevention. PMID- 29795794 TI - Social Relations and Technology: Continuity, Context, and Change. AB - Social relations, although basic to human nature, health and well-being, have become increasingly complicated as a result of changing population demography and technology. In this essay, we provide a historical overview of social relations, especially as they affect older people. We briefly review the evolution of theory and measurement surrounding social relations as well as early empirical evidence. We consider how social relations have changed over time as well as continuity and change regarding basic characteristics of social relations. Of special interest is the emerging influence of technology on how people maintain contact, especially the changing ways people can use technology to increase, decrease, maintain, or avoid social relations. We consider both negative and positive aspects of these new technologies and their influence on health and well-being. Finally, we conclude that new and emerging technologies hold great promise for the future by overcoming traditional barriers to maintaining social contact, support exchange, and information acquisition. Nevertheless, we caution that these new technologies can have the dehumanizing effect of distance thus creating the potential for insensitivity and increased negativity. In sum, we are cautiously optimistic about the promise of technology to expand, but not replace, traditional forms of social contact. PMID- 29795793 TI - Millennials and Their Parents: Implications of the New Young Adulthood for Midlife Adults. AB - The period of young adulthood has transformed dramatically over the past few decades. Today, scholars refer to "emerging adulthood" and "transitions to adulthood" to describe adults in their 20s. Prolonged youth has brought concomitant prolonged parenthood. This article addresses 3 areas of change in parent/child ties, increased (a) contact between generations, (b) support from parents to grown children as well as coresidence and (c) affection between the generations. We apply the Multidimensional Intergenerational Support Model (MISM) to explain these changes, considering societal (e.g., economic, technological), cultural, family demographic (e.g., fertility, stepparenting), relationship, and psychological (normative beliefs, affection) factors. Several theoretical perspectives (e.g., life course theory, family systems theory) suggest that these changes may have implications for the midlife parents' well-being. For example, parents may incur deleterious effects from (a) grown children's problems or (b) their own normative beliefs that offspring should be independent. Parents may benefit via opportunities for generativity with young adult offspring. Furthermore, current patterns may affect future parental aging. As parents incur declines of late life, they may be able to turn to caregivers with whom they have intimate bonds. Alternately, parents may be less able to obtain such care due to demographic changes involving grown children raising their own children later or who have never fully launched. It is important to consider shifts in the nature of young adulthood to prepare for midlife parents' future aging. PMID- 29795792 TI - Family Relationships and Well-Being. AB - Family relationships are enduring and consequential for well-being across the life course. We discuss several types of family relationships-marital, intergenerational, and sibling ties-that have an important influence on well being. We highlight the quality of family relationships as well as diversity of family relationships in explaining their impact on well-being across the adult life course. We discuss directions for future research, such as better understanding the complexities of these relationships with greater attention to diverse family structures, unexpected benefits of relationship strain, and unique intersections of social statuses. PMID- 29795796 TI - CD8 T Cell Memory Increases Immunopathology in the Perforin-Deficient Model of Hemophagocytic Lymphohistiocytosis Secondary to TNF-alpha. AB - Familial hemophagocytic lymphohistiocytosis 2 (FHL2) is a cytokine storm syndrome characterized by immune hyperactivation with viral infection due to a CD8 T cell cytotoxic killing defect secondary to a perforin deficiency. As most studies of FHL2 mice have used pathogen naive animals, the effects of immune memory on FHL2 are understudied. We utilized an immunization model of the perforin-deficient mouse to study the effects of immune memory on FHL2. Prior CD8 T cell specific antigen exposure leads to enhanced HLH disease with increased morbidity and decreased time to mortality. Enhanced disease is associated with altered cytokine production and T cell proliferation. Response to IFNgamma blockade is reduced and TNFalpha gains a pathogenic role, while blockade of the IL-33 receptor ST2 remains effective. These results suggest that pre-existing immune memory may worsen outcome and alter treatment response for FHL2 patients who may not be naive to their immune triggers. PMID- 29795795 TI - Assessing Dependency in a Multiethnic Community Cohort of Individuals With Alzheimer's Disease. AB - Background and Objectives: Clinic-based studies of patients with Alzheimer's disease (AD) have demonstrated the value of assessing dependence when characterizing patients' functional status. The Dependence Scale, a validated tool to assess level of caregiving needs, is associated with markers of disease severity, cost, and progression, while offering independent functional information about patients. This study examines whether such associations between the Dependence Scale and markers of disease severity demonstrated in clinical cohorts are similarly exhibited in a multiethnic community population of individuals with AD. Research Design and Methods: One hundred fifty four elders with AD enrolled in the Predictors 3 cohort were assessed with the Dependence Scale, modified Mini-Mental State Examination (mMMS), instrumental (IADL) and basic (BADL) activities of daily living, and Clinical Dementia Rating (CDR) Scale, and were assigned an Equivalent Institutional Care (EIC) rating. Cross sectional associations were examined using bivariate correlations and one-way analysis of variance analyses. Fisher-z tests examined differences in strengths of associations across previous clinic and current community cohorts. Results: Dependence Scale scores were associated with CDR (r = .20, p = .013), mMMS (r = .23, p = .005), IADL (r = .39, p < .001), BADL (r = .65, p < .001), and EIC (r = .51, p < .001). Dependence was unassociated with ethnicity (F[3,144] = 1.027, p = .3822), age (r = .120, p = .145), and education (r = -.053, p = .519). The strength of the correlations was comparable across cohorts except that BADLs were more strongly associated with dependence (z = -4.60, p < .001) in the community cohort, and living arrangement was not associated with dependence (r = .13, p = .130). Discussion and Implications: Associations between the Dependence Scale and markers of disease severity in a clinic-based cohort of AD patients are similar to associations in a multiethnic community cohort of individuals diagnosed with AD. The Dependence Scale relates to markers of disease severity rather than demographic factors, and may offer an unbiased assessment of care required in multiethnic and community populations. PMID- 29795797 TI - Correction to "Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure". AB - [This corrects the article DOI: 10.1021/acsmedchemlett.7b00263.]. PMID- 29795799 TI - Crowdsourcing Our National Gut. AB - The microbes of the human intestinal tract play a profound role in our health. The complex interactions between our gut microbial communities and the external environment, and the resulting functional consequences, can be difficult to disentangle. To address this problem, McDonald et al. (mSystems 3:e00031-18, 2018, https://doi.org/10.1128/mSystems.00031-18) present the first set of results from the American Gut Project, a citizen science-based data set currently comprised of over 10,000 gut microbiome samples and associated life history data. By combining this extensive data set with other published studies, the authors uncover novel relationships between gut microbiome structure and function. For example, they found that dietary plant diversity and recent antibiotic use predict both microbial and metabolomic diversity. McDonald et al. also demonstrate that there is high diversity across human gut microbiomes, even compared to the diversity of environmental microbiomes. The results from this study illuminate the potential of the citizen science approach to further our knowledge of host-associated microbial communities. PMID- 29795800 TI - Clinician Misperceptions about the Importance of Adolescent HPV Vaccination. AB - Introduction: Adolescent HPV vaccination rates remain suboptimal. The purpose of the study was to investigate attitudes about HPV vaccine relative to other adolescent vaccines among clinical staff from primary care offices and school based clinics. Methods: We interviewed clinicians in primary care offices and school-based clinics regarding their attitudes about HPV vaccine relative to Tdap and MCV4. Results: Respondents (n = 36) included clinical staff in family medicine (47%), pediatrics (25%), obstetrics/gynecology (19%) and school-based health clinics (8%). Only 3% strongly agreed and 17% agreed that completion of HPV vaccine was more important than completion of pertussis vaccine (Tdap), while 6% strongly agreed and 33% agreed that completion of HPV vaccine was more important than completion of meningitis vaccine (MCV4). Discussion: Providing clinicians with additional information about the cancer prevention benefits of the HPV vaccine and the greater risk for HPV infection/disease relative to other vaccine preventable adolescent diseases may help to increase HPV vaccination rates among adolescents. PMID- 29795798 TI - Clinical Characteristics and Angiographic Findings of Myocardial Infarction among Marijuana Users and Non-Users. AB - Background: Marijuana use has been increasingly legalized in the United States resulting in substantial rise in the number of users especially in the younger populations. While our group and others had described various metabolic effects of this drug, little is known about its association with acute myocardial infarction (AMI). Objective: This follow up study presents contemporaneous cohort of non-THC user patients at a single, urban center hospital diagnosed with ST elevation AMI; highlighting and comparing demographic, clinical, laboratory and angiographic characteristics based on exposure to THC at time of presentation. Methods: Retrospective chart review of patients with ST-elevation AMI presenting to our inner city hospital Coronary Care Unit over a period of 4 years (December 2013-April 2017). Results: Of the 10 case subjects studied whom presented with chest pain, EKG evidence of ST-elevation MI (STEMI) with cannabis use, mean age at presentation was 40 years old, which was 10 years younger than our control group with no marijuana use (n = 11, p = 0.107). Of the patients who had marijuana exposure upon admission, 3 (30%) had no known cardiovascular disease (CVD) risk factors (RF) on admission, 1 patient had 3 RF, 4 patients had 2 RF and 2 had 1 CVD risk factor, which included age, diabetes mellitus type 2 (DM2), hypertension, dyslipidemia, smoking status, and family history at time of triage. Patients who were negative for marijuana use had higher number of CVD risk factors present upon admission. ASCVD risk scores were 10% vs. 16% (p = 0.312). In angiographic findings, 100% of the marijuana users had 1 vessel disease compared with 55% in the non-users (p = 0.0351). Severity of stenosis for both groups was averaged at 93% for non-users vs 95% in THC users (p = 0.62414). Collateral vessels were visible during coronary arteriogram in 91% of non-THC users and in only 20% of THC users (p = 0.0019). Furthermore, non-users had 35% higher rate of Rentrop grade 1 collaterals (55% vs. 20%, p = 0.4872). Similar difference was shown in grade 2 collaterals between the two groups with non-users having 36% higher rate (36% vs. 0%, p = 0.0902). Amongst the patients who had collateral circulation present at the time of angiography (Rentrop grade >0), good collaterals (Rentrop grade 2 or 3) were present in 40% of non-THC users, while there was 0% presence of grade 2+ collaterals in THC users (p = 0.5152). Conclusion: In our study, marijuana use is associated with ST-elevation MI in largely minority population, occurring at a relatively younger age with half of the cases CVD risk free. Additional studies are needed to further characterize this population given the increase in marijuana use. PMID- 29795801 TI - Corrigendum: An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes. AB - [This corrects the article on p. 1566 in vol. 8, PMID: 29187854.]. PMID- 29795802 TI - Preventable Diabetic Complications After a Cancer Diagnosis in Patients With Diabetes: A Population-Based Cohort Study. AB - Background: A cancer diagnosis may disrupt diabetes management, increasing the risk of preventable complications. The objective was to determine whether a cancer diagnosis in patients with diabetes is associated with an increased risk of diabetic complications. Methods: This retrospective cohort study using health care data from Ontario, Canada, included persons age 50 years or older diagnosed with diabetes from 2007 to 2011 and followed until 2014. We examined the effects of cancer as a time-varying covariate: breast cancer (in women), prostate cancer (in men), colorectal cancer, and other cancers (in men and women). Each cancer exposure was categorized as stage I-III, IV, or unknown, and by time since cancer diagnosis (0-1 year, >1-3 years, and >3 years). The primary outcome was hospital visits for diabetic emergencies. Secondary outcomes were hospital visits for skin and soft tissue infections and cardiovascular events. Results: Of 817 060 patients with diabetes (mean age = 64.9 +/- 10.7 years), there were 9759 (1.2%) colorectal and 45 705 (5.6%) other cancers, 6714 (1.7%) breast cancers among 384 257 women and 10 331 (2.4%) prostate cancers among 432 803 men. For all cancers except stage I-III prostate cancer, rates of diabetic complications were significantly higher zero years to one year after diagnosis compared with no cancer (adjusted relative rates ranging from 1.26, 95% confidence interval [CI] = 1.08 to 1.49, to 4.07, 95% CI = 3.80 to 4.36); these differences were attenuated in the subsequent periods after cancer diagnosis. Conclusions: Patients with diabetes are at increased risk for preventable complications after a cancer diagnosis. Better diabetes care is needed during this vulnerable period. PMID- 29795803 TI - Corrigendum: Genomic and Genotypic Characterization of Cylindrospermopsis raciborskii: Toward an Intraspecific Phylogenetic Evaluation by Comparative Genomics. AB - [This corrects the article on p. 306 in vol. 9, PMID: 29535689.]. PMID- 29795804 TI - High-Throughput Screening Assay Datasets from the PubChem Database. AB - Availability of high-throughput screening (HTS) data in the public domain offers great potential to foster development of ligand-based computer-aided drug discovery (LB-CADD) methods crucial for drug discovery efforts in academia and industry. LB-CADD method development depends on high-quality HTS assay data, i.e., datasets that contain both active and inactive compounds. These active compounds are hits from primary screens that have been tested in concentration response experiments and where the target-specificity of the hits has been validated through suitable secondary screening experiments. Publicly available HTS repositories such as PubChem often provide such data in a convoluted way: compounds that are classified as inactive need to be extracted from the primary screening record. However, compounds classified as active in the primary screening record are not suitable as a set of active compounds for LB-CADD experiments due to high false-positive rate. A suitable set of actives can be derived by carefully analysing results in often up to five or more assays that are used to confirm and classify the activity of compounds. These assays, in part, build on each other. However, often not all hit compounds from the previous screen have been tested. Sometimes a compound can be classified as 'active', though its meaning is 'inactive' on the target of interest as it is 'active' on a different target protein. Here, a curation process of hierarchically related confirmatory screens is illustrated based on two specifically chosen protein use cases. The subsequent re-upload procedure into PubChem is described for the findings of those two scenarios. Further, we provide nine publicly accessible high quality datasets for future LB-CADD method development that provide a common baseline for comparison of future methods to the scientific community. We also provide a protocol researchers can follow to upload additional datasets for benchmarking. PMID- 29795805 TI - Diverse Aging and Health Inequality by Race and Ethnicity. AB - Although gerontologists have long embraced the concept of heterogeneity in theories and models of aging, recent research reveals the importance of racial and ethnic diversity on life course processes leading to health inequality. This article examines research on health inequality by race and ethnicity and identifies theoretical and methodological innovations that are transforming the study of health disparities. Drawing from cumulative inequality theory, we propose greater use of life course analysis, more attention to variability within racial and ethnic groups, and better integration of environmental context into the study of accumulation processes leading to health disparities. PMID- 29795807 TI - Corrigendum: Fucosylated Antigens in Cancer: An Alliance Toward Tumor Progression, Metastasis, and Resistance to Chemotherapy. AB - [This corrects the article on p. 39 in vol. 8, PMID: 29527514.]. PMID- 29795808 TI - Corrigendum: Using Aiptasia as a Model to Study Metabolic Interactions in Cnidarian-Symbiodinium Symbioses. AB - [This corrects the article on p. 214 in vol. 9, PMID: 29615919.]. PMID- 29795806 TI - Ameliorative potential of conditioning on ischemia-reperfusion injury in diabetes. AB - Diabetes is a serious metabolic disease characterized by hyperglycemia. Diabetes also leads to several long-term secondary complications. Cardiovascular disease is an important complication of diabetes and is a major contributor to morbidity and mortality in diabetic subjects. The discovery of conditioning-induced ischemic or anoxic tolerance has led to the demonstration of the protective potential of conditioning as a treatment strategy to mitigate ischemia reperfusion injury. Diabetes modulates multiple metabolic pathways and signal transduction cascades. Some of these pathways may overlap with mechanisms that mediate the beneficial effects of conditioning from the body's reaction to a sublethal insult, indicating the possibility of a potential interaction between diabetes and conditioning. Studies demonstrate that diabetes abrogates the ameliorative effect of various forms of conditioning, such as ischemic preconditioning, ischemic postconditioning, remote ischemic conditioning and pharmacological conditioning, on ischemia-reperfusion injury in various animal models. Moreover, drugs used to treat diabetes may have a potential impact on protection afforded by conditioning from ischemic injury. Studies also indicate a potential impact of various anti-diabetic drugs on conditioning-induced protection. Overall, the literature suggests that a better understanding of the overlap among pathways activated by diabetes and those involved in induction of ischemia tolerance may help identify ideal conditioning paradigms to protect diabetic subjects from ischemic injury. PMID- 29795810 TI - A Note on the Specification of Error Structures in Latent Interaction Models. AB - Latent interaction models have motivated a great deal of methodological research, mainly in the area of estimating such models. Product-indicator methods have been shown to be competitive with other methods of estimation in terms of parameter bias and standard error accuracy, and their continued popularity in empirical studies is due, in part, to their straightforward implementation and relative ease of estimation in mainstream structural equation modeling software. In recent years, the impact of different specifications of the mean structure of the structural model has been the focus of a fair amount of investigation in this area. Yet the effects of misspecification of the error structure of the observed variables implied by the model have not been investigated. In this study, the authors demonstrate algebraically the ramifications of misspecifying these error structures for the unconstrained product-indicator approach. Recommendations to practitioners based on these results are discussed. PMID- 29795811 TI - Anchor Selection Strategies for DIF Analysis: Review, Assessment, and New Approaches. AB - Differential item functioning (DIF) indicates the violation of the invariance assumption, for instance, in models based on item response theory (IRT). For item wise DIF analysis using IRT, a common metric for the item parameters of the groups that are to be compared (e.g., for the reference and the focal group) is necessary. In the Rasch model, therefore, the same linear restriction is imposed in both groups. Items in the restriction are termed the ''anchor items''. Ideally, these items are DIF-free to avoid artificially augmented false alarm rates. However, the question how DIF-free anchor items are selected appropriately is still a major challenge. Furthermore, various authors point out the lack of new anchor selection strategies and the lack of a comprehensive study especially for dichotomous IRT models. This article reviews existing anchor selection strategies that do not require any knowledge prior to DIF analysis, offers a straightforward notation, and proposes three new anchor selection strategies. An extensive simulation study is conducted to compare the performance of the anchor selection strategies. The results show that an appropriate anchor selection is crucial for suitable item-wise DIF analysis. The newly suggested anchor selection strategies outperform the existing strategies and can reliably locate a suitable anchor when the sample sizes are large enough. PMID- 29795812 TI - Maximum Likelihood Item Easiness Models for Test Theory Without an Answer Key. AB - Cultural consensus theory (CCT) is a data aggregation technique with many applications in the social and behavioral sciences. We describe the intuition and theory behind a set of CCT models for continuous type data using maximum likelihood inference methodology. We describe how bias parameters can be incorporated into these models. We introduce two extensions to the basic model in order to account for item rating easiness/difficulty. The first extension is a multiplicative model and the second is an additive model. We show how the multiplicative model is related to the Rasch model. We describe several maximum likelihood estimation procedures for the models and discuss issues of model fit and identifiability. We describe how the CCT models could be used to give alternative consensus-based measures of reliability. We demonstrate the utility of both the basic and extended models on a set of essay rating data and give ideas for future research. PMID- 29795813 TI - Multidimensional Classification of Examinees Using the Mixture Random Weights Linear Logistic Test Model. AB - An essential feature of the linear logistic test model (LLTM) is that item difficulties are explained using item design properties. By taking advantage of this explanatory aspect of the LLTM, in a mixture extension of the LLTM, the meaning of latent classes is specified by how item properties affect item difficulties within each class. To improve the interpretations of latent classes, this article presents a mixture generalization of the random weights linear logistic test model (RWLLTM). In detail, the present study considers individual differences in their multidimensional aspects, a general propensity (random intercept) and random coefficients of the item properties, as well as the differences among the fixed coefficients of the item properties. As an empirical illustration, data on verbal aggression were analyzed by comparing applications of the one- and two-class LLTM and RWLLTM. Results suggested that the two-class RWLLTM yielded better agreement with the empirical data than the other models. Moreover, relations between two random effects explained differences between the two classes detected by the mixture RWLLTM. Evidence from a simulation study indicated that the Bayesian estimation used in the present study appeared to recover the parameters in the mixture RWLLTM fairly well. PMID- 29795814 TI - Differentiation of Illusory and True Halo in Writing Scores. AB - This report summarizes an empirical study that addresses two related topics within the context of writing assessment-illusory halo and how much unique information is provided by multiple analytic scores. Specifically, we address the issue of whether unique information is provided by analytic scores assigned to student writing, beyond what is depicted by holistic scores, and to what degree multiple analytic scores assigned by a single rater display evidence of illusory halo. To that end, we analyze student responses to an expository writing prompt that were scored by six groups of raters-four groups assigned single analytic scores, one group assigned multiple analytic scores, and one group assigned holistic scores-using structural equation modeling. Our results suggest that there is evidence of illusory halo when raters assign multiple analytic scores to a single student response and that, at best, only two factors seem to be distinguishable in analytic writing scores assigned to expository essays. PMID- 29795815 TI - Investigating Measurement Invariance in Computer-Based Personality Testing: The Impact of Using Anchor Items on Effect Size Indices. AB - A popular method to assess measurement invariance of a particular item is based on likelihood ratio tests with all other items as anchor items. The results of this method are often only reported in terms of statistical significance, and researchers proposed different methods to empirically select anchor items. It is unclear, however, how many anchor items should be selected and which method will provide the "best" results using empirical data. In the present study, we examined the impact of using different numbers of anchor items on effect size indices when investigating measurement invariance on a personality questionnaire in two different assessment situations. Results suggested that the effect size indices were not influenced by using different numbers of anchor items. The values were comparable across different number of anchor items used and were small, which indicate that the effect of differential functioning at the item and test level is very small if not negligible. Practical implications are discussed and we discuss the use of anchor items and effect size indices in practice. PMID- 29795816 TI - A Direct Latent Variable Modeling Based Method for Point and Interval Estimation of Coefficient Alpha. AB - A direct approach to point and interval estimation of Cronbach's coefficient alpha for multiple component measuring instruments is outlined. The procedure is based on a latent variable modeling application with widely circulated software. As a by-product, using sample data the method permits ascertaining whether the population discrepancy between alpha and the composite reliability coefficient may be practically negligible for a given empirical setting. The outlined approach is illustrated with numerical data. PMID- 29795817 TI - Item Response Theory Models for Wording Effects in Mixed-Format Scales. AB - Many scales contain both positively and negatively worded items. Reverse recoding of negatively worded items might not be enough for them to function as positively worded items do. In this study, we commented on the drawbacks of existing approaches to wording effect in mixed-format scales and used bi-factor item response theory (IRT) models to test the assumption of reverse coding and evaluate the magnitude of the wording effect. The parameters of the bi-factor IRT models can be estimated with existing computer programs. Two empirical examples from the Program for International Student Assessment and the Trends in International Mathematics and Science Study were given to demonstrate the advantages of the bi-factor approach over traditional ones. It was found that the wording effect in these two data sets was substantial and that ignoring the wording effect resulted in overestimated test reliability and biased person measures. PMID- 29795818 TI - Real and Artificial Differential Item Functioning in Polytomous Items. AB - Differential item functioning (DIF) for an item between two groups is present if, for the same person location on a variable, persons from different groups have different expected values for their responses. Applying only to dichotomously scored items in the popular Mantel-Haenszel (MH) method for detecting DIF in which persons are classified by their total scores on an instrument, Andrich and Hagquist articulated the concept of artificial DIF and showed that as an artifact of the MH method, real DIF in one item favoring one group inevitably induces artificial DIF favoring the other group in all other items. Using the dichotomous Rasch model in which the total score for a person is a sufficient statistic, and therefore justifies classifying persons by their total scores, Andrich and Hagquist showed that to distinguish between real and artificial DIF in an item identified by the MH method, a sequential procedure for resolving items is implied. Using the polytomous Rasch model, this article generalizes the concept of artificial DIF to polytomous items, in which multiple item parameters play a role. The article shows that the same principle of resolving items sequentially as with dichotomous items applies also to distinguishing between real and artificial DIF with polytomous items. A real example and a small simulated example that parallels the real example are used illustratively. PMID- 29795819 TI - Rasch Mixture Models for DIF Detection: A Comparison of Old and New Score Specifications. AB - Rasch mixture models can be a useful tool when checking the assumption of measurement invariance for a single Rasch model. They provide advantages compared to manifest differential item functioning (DIF) tests when the DIF groups are only weakly correlated with the manifest covariates available. Unlike in single Rasch models, estimation of Rasch mixture models is sensitive to the specification of the ability distribution even when the conditional maximum likelihood approach is used. It is demonstrated in a simulation study how differences in ability can influence the latent classes of a Rasch mixture model. If the aim is only DIF detection, it is not of interest to uncover such ability differences as one is only interested in a latent group structure regarding the item difficulties. To avoid any confounding effect of ability differences (or impact), a new score distribution for the Rasch mixture model is introduced here. It ensures the estimation of the Rasch mixture model to be independent of the ability distribution and thus restricts the mixture to be sensitive to latent structure in the item difficulties only. Its usefulness is demonstrated in a simulation study, and its application is illustrated in a study of verbal aggression. PMID- 29795820 TI - Operationalizing Levels of Academic Mastery Based on Vygotsky's Theory: The Study of Mathematical Knowledge. AB - The present study tested the possibility of operationalizing levels of knowledge acquisition based on Vygotsky's theory of cognitive growth. An assessment tool (SAM-Math) was developed to capture a hypothesized hierarchical structure of mathematical knowledge consisting of procedural, conceptual, and functional levels. In Study 1, SAM-Math was administered to 4th-grade students (N = 2,216). The results of Rasch analysis indicated that the test provided an operational definition for the construct of mathematical competence that included the three levels of mastery corresponding to the theoretically based hierarchy of knowledge. In Study 2, SAM-Math was administered to students in 4th, 6th, 8th, and 10th grades (N = 396) to examine developmental changes in the levels of mathematics knowledge. The results showed that the mastery of mathematical concepts presented in elementary school continued to deepen beyond elementary school, as evidenced by a significant growth in conceptual and functional levels of knowledge. The findings are discussed in terms of their implications for psychological theory, test design, and educational practice. PMID- 29795809 TI - American Gut: an Open Platform for Citizen Science Microbiome Research. AB - Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples. PMID- 29795821 TI - a-Stratified Computerized Adaptive Testing in the Presence of Calibration Error. AB - a-Stratified computerized adaptive testing with b-blocking (AST), as an alternative to the widely used maximum Fisher information (MFI) item selection method, can effectively balance item pool usage while providing accurate latent trait estimates in computerized adaptive testing (CAT). However, previous comparisons of these methods have treated item parameter estimates as if they are the true population parameter values. Consequently, capitalization on chance may occur. In this article, we examined the performance of the AST method under more realistic conditions where item parameter estimates instead of true parameter values are used in the CAT. Its performance was compared against that of the MFI method when the latter is used in conjunction with Sympson-Hetter or randomesque exposure control. Results indicate that the MFI method, even when combined with exposure control, is susceptible to capitalization on chance. This is particularly true when the calibration sample size is small. On the other hand, AST is more robust to capitalization on chance. Consistent with previous investigations using true item parameter values, AST yields much more balanced item pool usage, with a small loss in the precision of latent trait estimates. The loss is negligible when the test is as long as 40 items. PMID- 29795822 TI - Development and Monte Carlo Study of a Procedure for Correcting the Standardized Mean Difference for Measurement Error in the Independent Variable. AB - The standardized mean difference (SMD) is perhaps the most important meta analytic effect size. It is typically used to represent the difference between treatment and control population means in treatment efficacy research. It is also used to represent differences between populations with different characteristics, such as persons who are depressed and those who are not. Measurement error in the independent variable (IV) attenuates SMDs. In this article, we derive a formula for the SMD that explicitly represents accuracy of classification of persons into populations on the basis of scores on an IV. We suggest an alternate version of the SMD less vulnerable to measurement error in the IV. We derive a novel approach to correcting the SMD for measurement error in the IV and show how this method can also be used to reliability correct the unstandardized mean difference. We compare this reliability correction approach with one suggested by Hunter and Schmidt in a series of Monte Carlo simulations. Finally, we consider how the proposed reliability correction method can be used in meta-analysis and suggest future directions for both research and further theoretical development of the proposed reliability correction method. PMID- 29795823 TI - Trends in Classroom Observation Scores. AB - Observations and ratings of classroom teaching and interactions collected over time are susceptible to trends in both the quality of instruction and rater behavior. These trends have potential implications for inferences about teaching and for study design. We use scores on the Classroom Assessment Scoring System Secondary (CLASS-S) protocol from 458 middle school teachers over a 2-year period to study changes over time in (a) the average quality of teaching for the population of teachers, (b) the average severity of the population of raters, and (c) the severity of individual raters. To obtain these estimates and assess them in the context of other factors that contribute to the variability in scores, we develop an augmented G study model that is broadly applicable for modeling sources of variability in classroom observation ratings data collected over time. In our data, we found that trends in teaching quality were small. Rater drift was very large during raters' initial days of observation and persisted throughout nearly 2 years of scoring. Raters did not converge to a common level of severity; using our model we estimate that variability among raters actually increases over the course of the study. Variance decompositions based on the model find that trends are a modest source of variance relative to overall rater effects, rater errors on specific lessons, and residual error. The discussion provides possible explanations for trends and rater divergence as well as implications for designs collecting ratings over time. PMID- 29795824 TI - An Effect Size Measure for Raju's Differential Functioning for Items and Tests. AB - This study established an effect size measure for differential functioning for items and tests' noncompensatory differential item functioning (NCDIF). The Mantel-Haenszel parameter served as the benchmark for developing NCDIF's effect size measure for reporting moderate and large differential item functioning in test items. The effect size of NCDIF is influenced by the model, the discrimination parameter, and the difficulty parameter. Therefore, tables of NCDIF's effect size were presented at given levels of a, b, and c parameters. In addition, a general effect size recommendation for moderate and large NCDIF is also established. PMID- 29795825 TI - Descriptive Statistics for Modern Test Score Distributions: Skewness, Kurtosis, Discreteness, and Ceiling Effects. AB - Many statistical analyses benefit from the assumption that unconditional or conditional distributions are continuous and normal. More than 50 years ago in this journal, Lord and Cook chronicled departures from normality in educational tests, and Micerri similarly showed that the normality assumption is met rarely in educational and psychological practice. In this article, the authors extend these previous analyses to state-level educational test score distributions that are an increasingly common target of high-stakes analysis and interpretation. Among 504 scale-score and raw-score distributions from state testing programs from recent years, nonnormal distributions are common and are often associated with particular state programs. The authors explain how scaling procedures from item response theory lead to nonnormal distributions as well as unusual patterns of discreteness. The authors recommend that distributional descriptive statistics be calculated routinely to inform model selection for large-scale test score data, and they illustrate consequences of nonnormality using sensitivity studies that compare baseline results to those from normalized score scales. PMID- 29795826 TI - Relationships Among Classical Test Theory and Item Response Theory Frameworks via Factor Analytic Models. AB - There are well-defined theoretical differences between the classical test theory (CTT) and item response theory (IRT) frameworks. It is understood that in the CTT framework, person and item statistics are test- and sample-dependent. This is not the perception with IRT. For this reason, the IRT framework is considered to be theoretically superior to the CTT framework for the purpose of estimating person and item parameters. In previous simulation studies, IRT models were used both as generating and as fitting models. Hence, results favoring the IRT framework could be attributed to IRT being the data-generation framework. Moreover, previous studies only considered the traditional CTT framework for the comparison, yet there is considerable literature suggesting that it may be more appropriate to use CTT statistics based on an underlying normal variable (UNV) assumption. The current study relates the class of CTT-based models with the UNV assumption to that of IRT, using confirmatory factor analysis to delineate the connections. A small Monte Carlo study was carried out to assess the comparability between the item and person statistics obtained from the frameworks of IRT and CTT with UNV assumption. Results show the frameworks of IRT and CTT with UNV assumption to be quite comparable, with neither framework showing an advantage over the other. PMID- 29795827 TI - Collinear Latent Variables in Multilevel Confirmatory Factor Analysis: A Comparison of Maximum Likelihood and Bayesian Estimations. AB - Because variables may be correlated in the social and behavioral sciences, multicollinearity might be problematic. This study investigates the effect of collinearity manipulated in within and between levels of a two-level confirmatory factor analysis by Monte Carlo simulation. Furthermore, the influence of the size of the intraclass correlation coefficient (ICC) and estimation method; maximum likelihood estimation with robust chi-squares and standard errors and Bayesian estimation, on the convergence rate are investigated. The other variables of interest were rate of inadmissible solutions and the relative parameter and standard error bias on the between level. The results showed that inadmissible solutions were obtained when there was between level collinearity and the estimation method was maximum likelihood. In the within level multicollinearity condition, all of the solutions were admissible but the bias values were higher compared with the between level collinearity condition. Bayesian estimation appeared to be robust in obtaining admissible parameters but the relative bias was higher than for maximum likelihood estimation. Finally, as expected, high ICC produced less biased results compared to medium ICC conditions. PMID- 29795828 TI - Type I and Type II Error Rates and Overall Accuracy of the Revised Parallel Analysis Method for Determining the Number of Factors. AB - Traditional parallel analysis (T-PA) estimates the number of factors by sequentially comparing sample eigenvalues with eigenvalues for randomly generated data. Revised parallel analysis (R-PA) sequentially compares the kth eigenvalue for sample data to the kth eigenvalue for generated data sets, conditioned on k- 1 underlying factors. T-PA and R-PA are conceptualized as stepwise hypothesis testing procedures and, thus, are alternatives to sequential likelihood ratio test (LRT) methods. We assessed the accuracy of T-PA, R-PA, and LRT methods using a Monte Carlo approach. Although no method was uniformly more accurate across all 180 conditions, the PA approaches outperformed LRT methods overall. Relative to T PA, R-PA tended to perform better within the framework of hypothesis testing and to evidence greater accuracy in conditions with higher factor loadings. PMID- 29795829 TI - Developing a Measure of General Academic Ability: An Application of Maximal Reliability and Optimal Linear Combination to High School Students' Scores. AB - This article is concerned with developing a measure of general academic ability (GAA) for high school graduates who apply to colleges, as well as with the identification of optimal weights of the GAA indicators in a linear combination that yields a composite score with maximal reliability and maximal predictive validity, employing the framework of the popular latent variable modeling methodology. The approach to achieving this goal is illustrated with data for 6,640 students with major in Science and 3,388 students with major in Art from colleges in Saudi Arabia. The indicators (observed measures) of the targeted GAA construct were selected from assessments that include the students' high school grade and their scores on two standardized tests developed by the National Center for Assessment in Higher Education in Saudi Arabia, General Aptitude Test (GAT) and Standardized Achievement Admission Test (SAAT). A unidimensional measure of GAA was developed initially, with different sets of indicators for colleges with major in Science and for colleges with major in Art. Appropriate indicators for colleges with major in Science were the high school grade, total score on GAT, and four SAAT subscales on Biology, Chemistry, Physics, and Math. With respect to colleges with major in Art, appropriate GAA indicators were the students' high school grade and their scores on GAT-Verbal, GAT-Quantitative, and SAAT. Although the case study is Saudi Arabia, the methods and procedures discussed in this article have broader utility and can be used in different contexts of educational and psychological assessment. PMID- 29795830 TI - The Effects of Q-Matrix Design on Classification Accuracy in the Log-Linear Cognitive Diagnosis Model. AB - Diagnostic classification models are psychometric models that aim to classify examinees according to their mastery or non-mastery of specified latent characteristics. These models are well-suited for providing diagnostic feedback on educational assessments because of their practical efficiency and increased reliability when compared with other multidimensional measurement models. A priori specifications of which latent characteristics or attributes are measured by each item are a core element of the diagnostic assessment design. This item attribute alignment, expressed in a Q-matrix, precedes and supports any inference resulting from the application of the diagnostic classification model. This study investigates the effects of Q-matrix design on classification accuracy for the log-linear cognitive diagnosis model. Results indicate that classification accuracy, reliability, and convergence rates improve when the Q-matrix contains isolated information from each measured attribute. PMID- 29795831 TI - Psychometric Properties of Measures of Team Diversity With Likert Data. AB - Certain diversity among team members is beneficial to the growth of an organization. Multiple measures have been proposed to quantify diversity, although little is known about their psychometric properties. This article proposes several methods to evaluate the unidimensionality and reliability of three measures of diversity. To approximate the interval scale required by the measures of diversity, a transformation on the Likert-item scores is proposed. Ridge maximum likelihood is used to deal with the issue of small sample size, and methods for evaluating the significance of the difference of two reliability estimates with correlated samples are also developed. Results with a real data set on entrepreneurial teams indicate that different measures of diversity may correspond to significantly different estimates of reliability. Results also indicate that diversity measures obtained with the transformed data tend to be more unidimensional than their counterparts obtained from Likert data. However, diversity measures obtained from Likert data tend to yield greater reliability estimates. Among the three examined measures of diversity, the standard deviation is found to yield greater and more efficient reliability estimates than the others and is thus recommended. PMID- 29795832 TI - A Cautionary Note on the Use of the Vale and Maurelli Method to Generate Multivariate, Nonnormal Data for Simulation Purposes. AB - To further understand the properties of data-generation algorithms for multivariate, nonnormal data, two Monte Carlo simulation studies comparing the Vale and Maurelli method and the Headrick fifth-order polynomial method were implemented. Combinations of skewness and kurtosis found in four published articles were run and attention was specifically paid to the quality of the sample estimates of univariate skewness and kurtosis. In the first study, it was found that the Vale and Maurelli algorithm yielded downward-biased estimates of skewness and kurtosis (particularly at small samples) that were also highly variable. This method was also prone to generate extreme sample kurtosis values if the population kurtosis was high. The estimates obtained from Headrick's algorithm were also biased downward, but much less so than the estimates obtained through Vale and Maurelli and much less variable. The second study reproduced the first simulation in the Curran, West, and Finch article using both the Vale and Maurelli method and the Heardick method. It was found that the chi-square values and empirical rejection rates changed depending on which data-generation method was used, sometimes sufficiently so that some of the original conclusions of the authors would no longer hold. In closing, recommendations are presented regarding the relative merits of each algorithm. PMID- 29795833 TI - Modeling Booklet Effects for Nonequivalent Group Designs in Large-Scale Assessment. AB - Multiple matrix designs are commonly used in large-scale assessments to distribute test items to students. These designs comprise several booklets, each containing a subset of the complete item pool. Besides reducing the test burden of individual students, using various booklets allows aligning the difficulty of the presented items to the assumed performance level of examined subgroups. While this may improve measurement precision and students' test-taking motivation, using several booklets might influence response behavior and thus constitute a potential source of unwanted variation. To provide guidance to identify and model booklet effects, this study presents statistical models accounting for booklet effects and applies these models in a large-scale assessment setting. Three models are derived from the Rasch model employing the generalized linear mixed models framework. The models were applied to data from a national educational standards assessment study for scientific competence. A total of 1,021 items were compiled to 74 booklets distributed to a sample of 9,044 students of Grades 9 and 10. The results revealed a small but nonnegligible booklet effect. For further large-scale assessment studies, it is recommended to examine whether booklet effects occur and to adequately account for them in the subsequent analyses where necessary. PMID- 29795834 TI - Using SAS PROC MCMC for Item Response Theory Models. AB - Interest in using Bayesian methods for estimating item response theory models has grown at a remarkable rate in recent years. This attentiveness to Bayesian estimation has also inspired a growth in available software such as WinBUGS, R packages, BMIRT, MPLUS, and SAS PROC MCMC. This article intends to provide an accessible overview of Bayesian methods in the context of item response theory to serve as a useful guide for practitioners in estimating and interpreting item response theory (IRT) models. Included is a description of the estimation procedure used by SAS PROC MCMC. Syntax is provided for estimation of both dichotomous and polytomous IRT models, as well as a discussion on how to extend the syntax to accommodate more complex IRT models. PMID- 29795835 TI - The Interaction of Ability Differences and Guessing When Modeling Differential Item Functioning With the Rasch Model: Conventional and Tailored Calibration. AB - In educational testing, differential item functioning (DIF) statistics must be accurately estimated to ensure the appropriate items are flagged for inspection or removal. This study showed how using the Rasch model to estimate DIF may introduce considerable bias in the results when there are large group differences in ability (impact) and the data follow a three-parameter logistic model. With large group ability differences, difficult non-DIF items appeared to favor the focal group and easy non-DIF items appeared to favor the reference group. Correspondingly, the effect sizes for DIF items were biased. These effects were mitigated when data were coded as missing for item-examinee encounters in which the person measure was considerably lower than the item location. Explanation of these results is provided by illustrating how the item response function becomes differentially distorted by guessing depending on the groups' ability distributions. In terms of practical implications, results suggest that measurement practitioners should not trust the DIF estimates from the Rasch model when there is a large difference in ability and examinees are potentially able to answer items correctly by guessing, unless data from examinees poorly matched to the item difficulty are coded as missing. PMID- 29795836 TI - The Importance of the Assumption of Uncorrelated Errors in Psychometric Theory. AB - A critical discussion of the assumption of uncorrelated errors in classical psychometric theory and its applications is provided. It is pointed out that this assumption is essential for a number of fundamental results and underlies the concept of parallel tests, the Spearman-Brown's prophecy and the correction for attenuation formulas as well as the discrepancy between observed and true correlations, and the upper bound property of the reliability index with respect to validity. These relationships are shown not to hold if the errors of considered pairs of tests are correlated. The assumption of lack of error correlation is demonstrated not to be testable using standard covariance structure analysis for pairs of indivisible measures evaluating the same true score with identical error variances. PMID- 29795837 TI - Differential Item Functioning Detection Across Two Methods of Defining Group Comparisons: Pairwise and Composite Group Comparisons. AB - This study compares two methods of defining groups for the detection of differential item functioning (DIF): (a) pairwise comparisons and (b) composite group comparisons. We aim to emphasize and empirically support the notion that the choice of pairwise versus composite group definitions in DIF is a reflection of how one defines fairness in DIF studies. In this study, a simulation was conducted based on data from a 60-item ACT Mathematics test (ACT; Hanson & Beguin). The unsigned area measure method (Raju) was used as the DIF detection method. An application to operational data was also completed in the study, as well as a comparison of observed Type I error rates and false discovery rates across the two methods of defining groups. Results indicate that the amount of flagged DIF or interpretations about DIF in all conditions were not the same across the two methods, and there may be some benefits to using composite group approaches. The results are discussed in connection to differing definitions of fairness. Recommendations for practice are made. PMID- 29795838 TI - Assessing Spurious Interaction Effects in Structural Equation Modeling: A Cautionary Note. AB - Several studies have stressed the importance of simultaneously estimating interaction and quadratic effects in multiple regression analyses, even if theory only suggests an interaction effect should be present. Specifically, past studies suggested that failing to simultaneously include quadratic effects when testing for interaction effects could result in Type I errors, Type II errors, or misleading interactions. Research investigating this issue has been limited to multiple regression models. Contrarily, structural equation modeling is a more appropriate analysis when hypotheses include latent variables. The current study utilized Monte Carlo simulation to investigate whether quadratic effects should be included in the latent variable interaction model. Consistent with previous research, it was found that including latent variable quadratic effects in the model successfully reduced the frequency of spurious interaction effects but at a cost of low power to detect true interaction effects, inaccurate parameter estimates, inaccurate standard error estimates, and reduced convergence rates. Based on findings from the current study, we recommend that researchers hypothesizing interactions between latent variables should test for these relations using the latent variable interaction model rather than the interaction quadratic model. If researchers are concerned about spurious interactions, then they may want to consider including quadratic effects in the model, provided that they have sample sizes of at least 500 and high indicator reliability. We caution all researchers to base higher order effects models on theory. PMID- 29795839 TI - An Alternative Way to Model Population Ability Distributions in Large-Scale Educational Surveys. AB - In large-scale educational surveys, a latent regression model is used to compensate for the shortage of cognitive information. Conventionally, the covariates in the latent regression model are principal components extracted from background data. This operational method has several important disadvantages, such as the handling of missing data and the high model complexity. The approach introduced here to identify multiple groups that can account for the variation among students is to conduct a latent class analysis (LCA). In the LCA, one or more latent nominal variables are identified that can be used to classify respondents with respect to their background characteristics. These classifications are then introduced as predictors in the latent regression. The primary goal of this study was to explore whether this approach yields similar estimates of group means and standard deviations compared with the operational procedure. The alternative approaches based on LCA differed regarding the number of classes, the items used for the LCA, and whether manifest class membership information or class membership probabilities were used as independent variables in the latent regression. Overall, recovery of the operational approach's group means and standard deviations was very satisfactory for all LCA approaches. Furthermore, the posterior means and standard deviations used to generate plausible values derived from the operational approach and the LCA approaches correlated highly. Thus, incorporating independent variables based on an LCA of background data into the latent regression model appears to be a viable alternative to the operational approach. PMID- 29795840 TI - Does Acquiescence Affect Individual Items Consistently? AB - Previous research has found the effects of acquiescence to be generally consistent across item aggregates within a single survey (i.e., essential tau equivalence), but it is unknown whether this phenomenon is consistent at the individual item level. This article evaluated the often assumed but inadequately tested proposition that individual items are affected by acquiescence to the same degree. We modeled an external acquiescence criterion to assess (a) whether it affected scale items consistently and (b) whether it would be strongly correlated with an acquiescence factor based on an assumption of tau-equivalence. The results did not support this assumption. As further evidence, we identified a situation in which this tau-equivalence assumption could potentially be violated. We propose that the response style be best understood within a framework of an acquiescence * item interaction. PMID- 29795841 TI - Reducing Bias and Error in the Correlation Coefficient Due to Nonnormality. AB - It is more common for educational and psychological data to be nonnormal than to be approximately normal. This tendency may lead to bias and error in point estimates of the Pearson correlation coefficient. In a series of Monte Carlo simulations, the Pearson correlation was examined under conditions of normal and nonnormal data, and it was compared with its major alternatives, including the Spearman rank-order correlation, the bootstrap estimate, the Box-Cox transformation family, and a general normalizing transformation (i.e., rankit), as well as to various bias adjustments. Nonnormality caused the correlation coefficient to be inflated by up to +.14, particularly when the nonnormality involved heavy-tailed distributions. Traditional bias adjustments worsened this problem, further inflating the estimate. The Spearman and rankit correlations eliminated this inflation and provided conservative estimates. Rankit also minimized random error for most sample sizes, except for the smallest samples (n = 10), where bootstrapping was more effective. Overall, results justify the use of carefully chosen alternatives to the Pearson correlation when normality is violated. PMID- 29795842 TI - The Evidence for a Subscore Structure in a Test of English Language Competency for English Language Learners. AB - How to compute and report subscores for a test that was originally designed for reporting scores on a unidimensional scale has been a topic of interest in recent years. In the research reported here, we describe an application of multidimensional item response theory to identify a subscore structure in a test designed for reporting results using a unidimensional scale. This research also dealt with the problem of planned missing data due to low levels of item overlap among multiple test forms. Furthermore, we provided evidence for the generalizability of the multidimensional structure using multiple forms of the same test. We also compared the subscores from multiple groups to show the usefulness of the subscores. The research provides evidence that subscores can be identified and produced to provide useful information about different constructs for multiple examinee groups even though the test data were well fit by a unidimensional model. PMID- 29795843 TI - Using a Model of Analysts' Judgments to Augment an Item Calibration Process. AB - When conducting item reviews, analysts evaluate an array of statistical and graphical information to assess the fit of a field test (FT) item to an item response theory model. The process can be tedious, particularly when the number of human reviews (HR) to be completed is large. Furthermore, such a process leads to decisions that are susceptible to human errors. A key finding from behavioral decision-making research has shown that a parametric model of human decision making often outperforms the decision maker himself. We exploit this finding by seeking a model to mimic how analysts integrate FT item level statistics and graphical performance plots to predict the analyst's assignment of the item's status. The procedure suggests a set of rules that achieves a desired level of classification accuracy, separating situations in which the evidence supports firm decisions from those situations that would likely benefit from HRs. Implementation of the decision rules accounts for an estimated 65% reduction in calibrations requiring HRs. PMID- 29795844 TI - Taking the Missing Propensity Into Account When Estimating Competence Scores: Evaluation of Item Response Theory Models for Nonignorable Omissions. AB - When competence tests are administered, subjects frequently omit items. These missing responses pose a threat to correctly estimating the proficiency level. Newer model-based approaches aim to take nonignorable missing data processes into account by incorporating a latent missing propensity into the measurement model. Two assumptions are typically made when using these models: (1) The missing propensity is unidimensional and (2) the missing propensity and the ability are bivariate normally distributed. These assumptions may, however, be violated in real data sets and could, thus, pose a threat to the validity of this approach. The present study focuses on modeling competencies in various domains, using data from a school sample (N = 15,396) and an adult sample (N = 7,256) from the National Educational Panel Study. Our interest was to investigate whether violations of unidimensionality and the normal distribution assumption severely affect the performance of the model-based approach in terms of differences in ability estimates. We propose a model with a competence dimension, a unidimensional missing propensity and a distributional assumption more flexible than a multivariate normal. Using this model for ability estimation results in different ability estimates compared with a model ignoring missing responses. Implications for ability estimation in large-scale assessments are discussed. PMID- 29795845 TI - Scale Reliability Evaluation With Heterogeneous Populations. AB - A latent variable modeling approach for scale reliability evaluation in heterogeneous populations is discussed. The method can be used for point and interval estimation of reliability of multicomponent measuring instruments in populations representing mixtures of an unknown number of latent classes or subpopulations. The procedure is helpful also for evaluation of possible between class reliability differences as well as of within-class reliability coefficients. The estimation approach can similarly be used in empirical settings with known class membership when distinct populations are investigated, their number is known beforehand and membership in them is observed for the studied subjects, or alternatively in settings where only the number of latent classes is known. A modification and extension of the method for evaluation of maximal reliability or coefficient alpha in heterogeneous populations are also outlined. The discussed procedure is illustrated with numerical data. PMID- 29795846 TI - Applying the Nominal Response Model Within a Longitudinal Framework to Construct the Positive Family Relationships Scale. AB - A psychometric analysis was conducted using the nominal response model under the item response theory framework to construct the Positive Family Relationships scale. Using data from the Fullerton Longitudinal Study, this scale was constructed within a long-term longitudinal framework spanning middle childhood through adolescence. Items tapping this construct were completed annually by mothers when children were aged 9 to 17 years. The scale measures a construct customized for each age with uniquely informative items consisting exclusively of discriminating response categories as evaluated using the nominal response model. By using longitudinal data, the study is innovative in implementing the method of test equating to a psychological construct across nine assessments spanning 8 years. Future research pertaining to validity is discussed. PMID- 29795847 TI - Detecting Test Tampering Using Item Response Theory. AB - Test tampering, especially on tests for educational accountability, is an unfortunate reality, necessitating that the state (or its testing vendor) perform data forensic analyses, such as erasure analyses, to look for signs of possible malfeasance. Few statistical approaches exist for detecting fraudulent erasures, and those that do largely do not lend themselves to making probabilistic statements about the likelihood of the observations. In this article, a new erasure detection index, EDI, is developed, which uses item response theory to compare the number of observed wrong-to-right erasures to the number expected due to chance, conditional on the examinee's ability-level and number of erased items. A simulation study is presented to evaluate the Type I error rate and power of EDI under various types of fraudulent and benign erasures. Results show that EDI with a correction for continuity yields Type I error rates that are less than or equal to nominal levels for every condition studied, and has high power to detect even small amounts of tampering among the students for whom tampering is most likely. PMID- 29795848 TI - Best Design for Multidimensional Computerized Adaptive Testing With the Bifactor Model. AB - Most computerized adaptive tests (CATs) have been studied using the framework of unidimensional item response theory. However, many psychological variables are multidimensional and might benefit from using a multidimensional approach to CATs. This study investigated the accuracy, fidelity, and efficiency of a fully multidimensional CAT algorithm (MCAT) with a bifactor model using simulated data. Four item selection methods in MCAT were examined for three bifactor pattern designs using two multidimensional item response theory models. To compare MCAT item selection and estimation methods, a fixed test length was used. The Ds optimality item selection improved theta estimates with respect to a general factor, and either D- or A-optimality improved estimates of the group factors in three bifactor pattern designs under two multidimensional item response theory models. The MCAT model without a guessing parameter functioned better than the MCAT model with a guessing parameter. The MAP (maximum a posteriori) estimation method provided more accurate theta estimates than the EAP (expected a posteriori) method under most conditions, and MAP showed lower observed standard errors than EAP under most conditions, except for a general factor condition using Ds-optimality item selection. PMID- 29795849 TI - A Ratio Test of Interrater Agreement With High Specificity. AB - Existing tests of interrater agreements have high statistical power; however, they lack specificity. If the ratings of the two raters do not show agreement but are not random, the current tests, some of which are based on Cohen's kappa, will often reject the null hypothesis, leading to the wrong conclusion that agreement is present. A new test of interrater agreement, applicable to nominal or ordinal categories, is presented. The test statistic can be expressed as a ratio (labeled QA , ranging from 0 to infinity) or as a proportion (labeled PA , ranging from 0 to 1). This test weighs information supporting agreement with information supporting disagreement. This new test's effectiveness (power and specificity) is compared with five other tests of interrater agreement in a series of Monte Carlo simulations. The new test, although slightly less powerful than the other tests reviewed, is the only one sensitive to agreement only. We also introduce confidence intervals on the proportion of agreement. PMID- 29795850 TI - Investigation of Response Changes in the GRE Revised General Test. AB - Research on examinees' response changes on multiple-choice tests over the past 80 years has yielded some consistent findings, including that most examinees make score gains by changing answers. This study expands the research on response changes by focusing on a high-stakes admissions test-the Verbal Reasoning and Quantitative Reasoning measures of the GRE revised General Test. We analyzed data from 8,538 examinees for Quantitative and 9,140 for Verbal sections who took the GRE revised General Test in 12 countries. The analyses yielded findings consistent with prior research. In addition, as examinees' ability increases, the benefit of response changing increases. The study yielded significant implications for both test agencies and test takers. Computer adaptive tests often do not allow the test takers to review and revise. Findings from this study confirm the benefit of such features. PMID- 29795851 TI - Effects of Design Properties on Parameter Estimation in Large-Scale Assessments. AB - The selection of an appropriate booklet design is an important element of large scale assessments of student achievement. Two design properties that are typically optimized are the balance with respect to the positions the items are presented and with respect to the mutual occurrence of pairs of items in the same booklet. The purpose of this study is to investigate the effects of these two design properties on bias and root mean square error of item parameter estimates from the Rasch model. First, position effects are estimated using data from a large-scale assessment study measuring the competencies of 19,107 ninth graders in science. These results were then used for a simulation study with 1,540 booklet designs with systematically varied position balance and cluster pair balance. The simulation results showed a small effect of position balancing on bias and root mean square error of the item parameter estimates while the cluster pair balance was ignorable. This null effect is actually good news for test designers since it allows for deliberately reducing the degree of cluster pair balance without negative effects on item parameter estimates. However, it is recommended to try to achieve a high position balance when designing large-scale assessment studies. PMID- 29795852 TI - Does Matching Quality Matter in Mode Comparison Studies? AB - This article provides a brief overview and comparison of three matching approaches in forming comparable groups for a study comparing test administration modes (i.e., computer-based tests [CBT] and paper-and-pencil tests [PPT]): (a) a propensity score matching approach proposed in this article, (b) the propensity score matching approach used by Lottridge, Nicewander, and Mitzel, and (c) a modified approach of matched samples comparability analyses (MSCA) mentioned by Way, Davis, and Fitzpatrick. Different matching approaches resulted in different matched data with differing degrees of matching quality, and matched data from each matching approach were then used in the mode comparison investigation. Construct equivalence was examined and the level of invariance was found to be consistent across modes for all three matching approaches. Raw-to-scale score conversion tables were created, and the impact on CBT students' proficiency classification was examined. The comparison of the number of CBT students whose proficiency classification would be affected and the equality of score distributions between modes on raw scores and scale scores across the three matching approaches indicate that the propensity score matching approach delineated in this article led to the most consistent evidence for the conclusion of the mode comparison. PMID- 29795853 TI - Intraclass Correlation Coefficients in Hierarchical Design Studies With Discrete Response Variables: A Note on a Direct Interval Estimation Procedure. AB - A latent variable modeling procedure that can be used to evaluate intraclass correlation coefficients in two-level settings with discrete response variables is discussed. The approach is readily applied when the purpose is to furnish confidence intervals at prespecified confidence levels for these coefficients in setups with binary or ordinal outcome measures and nesting of subjects within higher order units. The method can aid educational and behavioral researchers in their study of sources of observed outcome variability and model choice considerations in multilevel settings, and is illustrated with empirical survey data. PMID- 29795854 TI - Accuracy of Revised and Traditional Parallel Analyses for Assessing Dimensionality with Binary Data. AB - Parallel analysis (PA) is a useful empirical tool for assessing the number of factors in exploratory factor analysis. On conceptual and empirical grounds, we argue for a revision to PA that makes it more consistent with hypothesis testing. Using Monte Carlo methods, we evaluated the relative accuracy of the revised PA (R-PA) and traditional PA (T-PA) methods for factor analysis of tetrachoric correlations between items with binary responses. We manipulated five data generation factors: number of observations, type of factor model, factor loadings, correlation between factors, and distribution of thresholds. The R-PA method tended to be more accurate than T-PA, although not uniformly across conditions. R-PA tended to perform better relative to T-PA if the underlying model (a) was unidimensional but had some unique items, (b) had highly correlated factors, or (c) had a general factor as well as a group factor. In addition, R-PA tended to outperform T-PA if items had higher factor loadings and sample size was large. A major disadvantage of the T-PA method was that it frequently yielded inflated Type I error rates. PMID- 29795855 TI - Item Response Theory With Covariates (IRT-C): Assessing Item Recovery and Differential Item Functioning for the Three-Parameter Logistic Model. AB - In large-scale testing, the use of multigroup approaches is limited for assessing differential item functioning (DIF) across multiple variables as DIF is examined for each variable separately. In contrast, the item response theory with covariate (IRT-C) procedure can be used to examine DIF across multiple variables (covariates) simultaneously. To assess the utility of the IRT-C procedure, we conducted a simulation study. Using SAT data for realistic parameters, uniform DIF on three covariates were simulated: gender (dichotomous), race/ethnicity (categorical), and income (continuous). Simulations were conducted across several conditions: two test lengths (14 items, 21 items), four sample sizes (5,000, 10,000, 20,000, 40,000), and two DIF effect sizes (medium, large). It was found that the IRT-C procedure could accurately recover the latent means and the three parameter logistic model parameters well with a substantial sample size of 20,000. There was good control of Type I error rates to the nominal rates across the sample sizes. Good power to detect DIF across all covariates (>.80) was observed when the sample size was 20,000 for large DIF effect size and 40,000 for medium DIF effect size. Practical implications for the use of the IRT-C procedure are discussed. PMID- 29795856 TI - The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF. AB - Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item. PMID- 29795857 TI - Alternative Models for Small Samples in Psychological Research: Applying Linear Mixed Effects Models and Generalized Estimating Equations to Repeated Measures Data. AB - Unavoidable sample size issues beset psychological research that involves scarce populations or costly laboratory procedures. When incorporating longitudinal designs these samples are further reduced by traditional modeling techniques, which perform listwise deletion for any instance of missing data. Moreover, these techniques are limited in their capacity to accommodate alternative correlation structures that are common in repeated measures studies. Researchers require sound quantitative methods to work with limited but valuable measures without degrading their data sets. This article provides a brief tutorial and exploration of two alternative longitudinal modeling techniques, linear mixed effects models and generalized estimating equations, as applied to a repeated measures study (n = 12) of pairmate attachment and social stress in primates. Both techniques provide comparable results, but each model offers unique information that can be helpful when deciding the right analytic tool. PMID- 29795858 TI - Reweighting Data in the Spirit of Tukey: Using Bayesian Posterior Probabilities as Rasch Residuals for Studying Misfit. AB - A new variant of the iterative "data = fit + residual" data-analytical approach described by Mosteller and Tukey is proposed and implemented in the context of item response theory psychometric models. Posterior probabilities from a Bayesian mixture model of a Rasch item response theory model and an unscalable latent class are expressed as weights for the original data. The data are weighted by the units' posterior probabilities for the unscalable class and used for further exploration of structures. Factor analysis models are compared with the original data and data as reweighted by the posterior probabilities for the unscalable class. In comparing two weighted data sets, Rasch-weighted data and data considered unscalable, differences were evident. Pattern types are detected for the Rasch baseline with patterns that are different patterns from random or systematic contamination. Rasch baseline patterns are strongest near item difficulties closest to the mean generating value of thetas. Patterns in baseline conditions are weaker as they depart from an item difficulty of zero and move toward extreme values. Random contamination patterns are typically flat and near zero regardless of item difficulty. Systematic contamination using reversed Rasch generated data produced alternate patterns to the Rasch baseline condition and in some conditions showed an opposite effect from Rasch patterns. Differences could be detected within residually weighted data between the Rasch-generated subtest and contaminated subtest. Rasch subtest often had Rasch patterns while contaminated subtest had random/flat or systematic/reversed pattern. PMID- 29795859 TI - It Might Not Make a Big DIF: Improved Differential Test Functioning Statistics That Account for Sampling Variability. AB - Differential test functioning, or DTF, occurs when one or more items in a test demonstrate differential item functioning (DIF) and the aggregate of these effects are witnessed at the test level. In many applications, DTF can be more important than DIF when the overall effects of DIF at the test level can be quantified. However, optimal statistical methodology for detecting and understanding DTF has not been developed. This article proposes improved DTF statistics that properly account for sampling variability in item parameter estimates while avoiding the necessity of predicting provisional latent trait estimates to create two-step approximations. The properties of the DTF statistics were examined with two Monte Carlo simulation studies using dichotomous and polytomous IRT models. The simulation results revealed that the improved DTF statistics obtained optimal and consistent statistical properties, such as obtaining consistent Type I error rates. Next, an empirical analysis demonstrated the application of the proposed methodology. Applied settings where the DTF statistics can be beneficial are suggested and future DTF research areas are proposed. PMID- 29795860 TI - The Matching Criterion Purification for Differential Item Functioning Analyses in a Large-Scale Assessment. AB - The current study investigated the impact of matching criterion purification on the accuracy of differential item functioning (DIF) detection in large-scale assessments. The three matching approaches for DIF analyses (block-level matching, pooled booklet matching, and equated pooled booklet matching) were employed with the Mantel-Haenszel procedure. Five factors-the length of a test, the proportion of items exhibiting DIF, a sample size, a ratio of a reference and focal group, and the existence of an average ability difference between two groups-were manipulated. The three matching approaches were used with and without purification. Also, a systematic test form difference was considered. The results indicated that overall, matching criterion purification in the three approaches contributed to the improvement of power in the detection of DIF. Depending on the psychometric characteristics of items exhibiting DIF and the existence of an average ability difference, the amount of power improvement due to matching criterion purification was different across the three approaches. The purification of a matching criterion contributed to the slight reduction of Type I error rates in the three approaches when no mean ability difference existed between the two groups. Considering power improvement with the control of Type I error rates, the purification of a matching criterion in the pooled booklet matching and the equated pooled booklet matching approaches can be recommended for DIF analyses in large-scale assessments. PMID- 29795861 TI - Further Considerations in Using Items With Diverse Content to Measure Acquiescence. AB - To measure the response style of acquiescence, researchers recommend the use of at least 15 items with heterogeneous content. Such an approach is consistent with its theoretical definition and is a substantial improvement over traditional methods. Nevertheless, measurement of acquiescence can be enhanced by two additional considerations: first, to ensure that it is not confounded with item valence, equal numbers of positively and negatively phrased items should be used; second, the validity of acquiescence scores can be substantially improved when derived from more than 15 items: about twice that number appears to be the minimum. These issues are illustrated empirically and recommendations are made for research practice. PMID- 29795862 TI - A Latent Transition Analysis Model for Assessing Change in Cognitive Skills. AB - Latent transition analysis (LTA) was initially developed to provide a means of measuring change in dynamic latent variables. In this article, we illustrate the use of a cognitive diagnostic model, the DINA model, as the measurement model in a LTA, thereby demonstrating a means of analyzing change in cognitive skills over time. An example is presented of an instructional treatment on a sample of seventh-grade students in several classrooms in a Midwestern school district. In the example, it is demonstrated how hypotheses could be framed and then tested regarding the form of the change in different groups within the population. Both manifest and latent groups also are defined and used to test additional hypotheses about change specific to particular subpopulations. Results suggest that the use of a DINA measurement model expands the utility of LTA to practical problems in educational measurement research. PMID- 29795863 TI - Evaluating the Impact of Guessing and Its Interactions With Other Test Characteristics on Confidence Interval Procedures for Coefficient Alpha. AB - The effect of guessing on the point estimate of coefficient alpha has been studied in the literature, but the impact of guessing and its interactions with other test characteristics on the interval estimators for coefficient alpha has not been fully investigated. This study examined the impact of guessing and its interactions with other test characteristics on four confidence interval (CI) procedures for coefficient alpha in terms of coverage rate (CR), length, and the degree of asymmetry of CI estimates. In addition, interval estimates of coefficient alpha when data follow the essentially tau-equivalent condition were investigated as a supplement to the case of dichotomous data with examinee guessing. For dichotomous data with guessing, the results did not reveal salient negative effects of guessing and its interactions with other test characteristics (sample size, test length, coefficient alpha levels) on CR and the degree of asymmetry, but the effect of guessing was salient as a main effect and an interaction effect with sample size on the length of the CI estimates, making longer CI estimates as guessing increases, especially when combined with a small sample size. Other important effects (e.g., CI procedures on CR) are also discussed. PMID- 29795864 TI - Partially Compensatory Multidimensional Item Response Theory Models: Two Alternate Model Forms. AB - Partially compensatory models may capture the cognitive skills needed to answer test items more realistically than compensatory models, but estimating the model parameters may be a challenge. Data were simulated to follow two different partially compensatory models, a model with an interaction term and a product model. The model parameters were then estimated for both models and for the compensatory model. Either the model used to simulate the data or the compensatory model generally had the best fit, as indexed by information criteria. Interfactor correlations were estimated well by both the correct model and the compensatory model. The predicted response probabilities were most accurate from the model used to simulate the data. Regarding item parameters, root mean square errors seemed reasonable for the interaction model but were quite large for some items for the product model. Thetas were recovered similarly by all models, regardless of the model used to simulate the data. PMID- 29795865 TI - Unidimensional IRT Item Parameter Estimates Across Equivalent Test Forms With Confounding Specifications Within Dimensions. AB - When constructing multiple test forms, the number of items and the total test difficulty are often equivalent. Not all test developers match the number of items and/or average item difficulty within subcontent areas. In this simulation study, six test forms were constructed having an equal number of items and average item difficulty overall. Manipulated variables were the number of items and average item difficulty within subsets of items primarily measuring one of two dimensions. Data sets were simulated at four levels of correlation (0, .3, .6, and .9). Item parameters were estimated using the Rasch and two-parameter logistic unidimensional item response theory models. Estimated discrimination and difficulty were compared across forms and to the true item parameters. The average unidimensional estimated discrimination was consistent across forms having the same correlation. Forms having a larger set of easy items measuring one dimension were estimated as being more difficult than forms having a larger set of hard items. Estimates were also investigated within subsets of items, and measures of bias were reported. This study encourages test developers to not only maintain consistent test specifications across forms as a whole but also within subcontent areas. PMID- 29795866 TI - Automatic Coding of Short Text Responses via Clustering in Educational Assessment. AB - Automatic coding of short text responses opens new doors in assessment. We implemented and integrated baseline methods of natural language processing and statistical modelling by means of software components that are available under open licenses. The accuracy of automatic text coding is demonstrated by using data collected in the Programme for International Student Assessment (PISA) 2012 in Germany. Free text responses of 10 items with [Formula: see text] responses in total were analyzed. We further examined the effect of different methods, parameter values, and sample sizes on performance of the implemented system. The system reached fair to good up to excellent agreement with human codings [Formula: see text] Especially items that are solved by naming specific semantic concepts appeared properly coded. The system performed equally well with [Formula: see text] and somewhat poorer but still acceptable down to [Formula: see text] Based on our findings, we discuss potential innovations for assessment that are enabled by automatic coding of short text responses. PMID- 29795867 TI - A Simulation Study on Methods of Correcting for the Effects of Extreme Response Style. AB - The impact of response styles such as extreme response style (ERS) on trait estimation has long been a matter of concern to researchers and practitioners. This simulation study investigated three methods that have been proposed for the correction of trait estimates for ERS effects: (a) mixed Rasch models, (b) multidimensional item response models, and (c) regression residuals. The methods were compared with respect to their ability of recovering the true latent trait levels. Data were generated according to a unidimensional model with only one trait, a mixed Rasch model with two populations of ERS and non-ERS, and a two dimensional model incorporating a trait and an ERS dimension. The data were analyzed using the same models as well as linear regression where the trait estimate is regressed on an ERS score and the resulting residual is considered the corrected trait estimate. Over all conditions, the two-dimensional model achieved the best trait recovery, though the difference to the unidimensional model was rather small. Mixed Rasch models were in general inferior to the other correction methods. When the trait and ERS showed no to weak correlations, ERS appeared to have a minor impact on trait estimation. PMID- 29795868 TI - On the Relationship Between Classical Test Theory and Item Response Theory: From One to the Other and Back. AB - The frequently neglected and often misunderstood relationship between classical test theory and item response theory is discussed for the unidimensional case with binary measures and no guessing. It is pointed out that popular item response models can be directly obtained from classical test theory-based models by accounting for the discrete nature of the observed items. Two distinct observational equivalence approaches are outlined that render the item response models from corresponding classical test theory-based models, and can each be used to obtain the former from the latter models. Similarly, classical test theory models can be furnished using the reverse application of either of those approaches from corresponding item response models. PMID- 29795869 TI - Testing Mediation in Structural Equation Modeling: The Effectiveness of the Test of Joint Significance. AB - A large number of approaches have been proposed for estimating and testing the significance of indirect effects in mediation models. In this study, four sets of Monte Carlo simulations involving full latent variable structural equation models were run in order to contrast the effectiveness of the currently popular bias corrected bootstrapping approach with the simple test of joint significance approach. The results from these simulations demonstrate that the test of joint significance had more power than bias-corrected bootstrapping and also yielded more reasonable Type I errors. PMID- 29795870 TI - Robust Coefficients Alpha and Omega and Confidence Intervals With Outlying Observations and Missing Data: Methods and Software. AB - Cronbach's coefficient alpha is a widely used reliability measure in social, behavioral, and education sciences. It is reported in nearly every study that involves measuring a construct through multiple items. With non-tau-equivalent items, McDonald's omega has been used as a popular alternative to alpha in the literature. Traditional estimation methods for alpha and omega often implicitly assume that data are complete and normally distributed. This study proposes robust procedures to estimate both alpha and omega as well as corresponding standard errors and confidence intervals from samples that may contain potential outlying observations and missing values. The influence of outlying observations and missing data on the estimates of alpha and omega is investigated through two simulation studies. Results show that the newly developed robust method yields substantially improved alpha and omega estimates as well as better coverage rates of confidence intervals than the conventional nonrobust method. An R package coefficientalpha is developed and demonstrated to obtain robust estimates of alpha and omega. PMID- 29795871 TI - Controlling Guessing Bias in the Dichotomous Rasch Model Applied to a Large Scale, Vertically Scaled Testing Program. AB - Recent research has shown how the statistical bias in Rasch model difficulty estimates induced by guessing in multiple-choice items can be eliminated. Using vertical scaling of a high-profile national reading test, it is shown that the dominant effect of removing such bias is a nonlinear change in the unit of scale across the continuum. The consequence is that the proficiencies of the more proficient students are increased relative to those of the less proficient. Not controlling the guessing bias underestimates the progress of students across 7 years of schooling with important educational implications. PMID- 29795872 TI - A Comparison of Composite Reliability Estimators: Coefficient Omega Confidence Intervals in the Current Literature. AB - Coefficient omega and alpha are both measures of the composite reliability for a set of items. Unlike coefficient alpha, coefficient omega remains unbiased with congeneric items with uncorrelated errors. Despite this ability, coefficient omega is not as widely used and cited in the literature as coefficient alpha. Reasons for coefficient omega's underutilization include a limited knowledge of its statistical properties. However, consistent efforts to understand the statistical properties of coefficient omega can help improve its utilization in research efforts. Here, six approaches for estimating confidence intervals for coefficient omega with unidimensional congeneric items were evaluated through a Monte Carlo simulation. The evaluations were made through simulation conditions that mimic realistic conditions that investigators are likely to face in applied work, including items that are not normally distributed and small sample size(s). Overall, the normal theory bootstrap confidence interval had the best performance across all simulation conditions that included sample sizes less than 100. However, most methods had sound coverage with sample sizes of 100 or more. PMID- 29795873 TI - Can Reliability of Multiple Component Measuring Instruments Depend on Response Option Presentation Mode? AB - This article examines the possible dependency of composite reliability on presentation format of the elements of a multi-item measuring instrument. Using empirical data and a recent method for interval estimation of group differences in reliability, we demonstrate that the reliability of an instrument need not be the same when polarity of the response options for its individual components differs across administrations of the instrument. Implications for empirical educational, behavioral, and social research are discussed. PMID- 29795874 TI - A Comprehensive Regression-Based Approach for Identifying Sources of Person Misfit in Typical-Response Measures. AB - This article proposes a general parametric item response theory approach for identifying sources of misfit in response patterns that have been classified as potentially inconsistent by a global person-fit index. The approach, which is based on the weighted least squared regression of the observed responses on the model-expected responses, can be used with a variety of unidimensional and multidimensional models intended for binary, graded, and continuous responses and consists of procedures for identifying (a) general deviation trends, (b) local inconsistencies, and (c) single response inconsistencies. A free program called REG-PERFIT that implements most of the proposed techniques has been developed, described, and made available for interested researchers. Finally, the functioning and usefulness of the proposed procedures is illustrated with an empirical study based on a statistics-anxiety scale. PMID- 29795875 TI - Convergence, Admissibility, and Fit of Alternative Confirmatory Factor Analysis Models for MTMM Data. AB - We compared six different analytic models for multitrait-multimethod (MTMM) data in terms of convergence, admissibility, and model fit to 258 samples of previously reported data. Two well-known models, the correlated trait-correlated method (CTCM) and the correlated trait-correlated uniqueness (CTCU) models, were fit for reference purposes in comparison to four other under- or unstudied models, including (a) Rindskopf's reparameterization of the CTCM (CTCM-R) model, (b) a correlated trait-constrained uncorrelated method model and two of its more general cases, (c) a correlated trait-constrained correlated method model, and (d) a correlated trait-uncorrelated method model. Results show that (a) the CTCM R model often solved convergence and admissibility problems with the CTCM model at rates equivalent to the CTCU model and (b) constrained models often provided convergent and admissible solutions but significantly worse model fit, indicating that they are often not plausible when analyzing real data. A follow-up simulation study showed that the CTCM-R model also provided the most accurate estimates of the full range of parameters relevant to a confirmatory factor analytic model of MTMM data. PMID- 29795876 TI - How Does Calibration Timing and Seasonality Affect Item Parameter Estimates? AB - Continuously administered examination programs, particularly credentialing programs that require graduation from educational programs, often experience seasonality where distributions of examine ability may differ over time. Such seasonality may affect the quality of important statistical processes, such as item response theory (IRT) item calibration and equating. The lead time required for producing pre-equated test forms in the continuous testing framework further complicates issues. This study examines the effect of seasonality in test data on Rasch IRT item parameter estimates. Data came from four credentialing examination programs that represented both programs with and without seasonality, as well as medium and low examinee volume. Results showed that calibrating items during certain times can lead to quite poor item parameter estimates. While certain programs could conduct IRT calibrations without waiting for the full examination cycle to be completed, other types of programs should wait as long as possible before calibrating items. PMID- 29795877 TI - The Role of Measurement Quality on Practical Guidelines for Assessing Measurement and Structural Invariance. AB - Although differences in goodness-of-fit indices (DeltaGOFs) have been advocated for assessing measurement invariance, studies that advanced recommended differential cutoffs for adjudicating invariance actually utilized a very limited range of values representing the quality of indicator variables (i.e., magnitude of loadings). Because quality of measurement has been found to be relevant in the context of assessing data-model fit in single-group models, this study used simulation and population analysis methods to examine the extent to which quality of measurement affects DeltaGOFs for tests of invariance in multiple group models. Results show that DeltaMcDonald's NCI is minimally affected by loading magnitude and sample size when testing invariance in the measurement model, while differences in comparative fit index varies widely when testing both measurement and structural variance as measurement quality changes, making it difficult to pinpoint a common value that suggests reasonable invariance. PMID- 29795878 TI - A Mixture Proportional Hazards Model With Random Effects for Response Times in Tests. AB - In this article, a new model for test response times is proposed that combines latent class analysis and the proportional hazards model with random effects in a similar vein as the mixture factor model. The model assumes the existence of different latent classes. In each latent class, the response times are distributed according to a class-specific proportional hazards model. The class specific proportional hazards models relate the response times of each subject to his or her work pace, which is considered as a random effect. The latent class extension of the proportional hazards model allows for differences in response strategies between subjects. The differences can be captured in the hazard functions, which trace the progress individuals make over time when working on an item. The model can be calibrated with marginal maximum likelihood estimation. The fit of the model can either be assessed with information criteria or with a test of model fit. In a simulation study, the performance of the proposed approaches to model calibration and model evaluation is investigated. Finally, the model is used for a real data set. PMID- 29795879 TI - Effects of Interim Assessments Across the Achievement Distribution: Evidence From an Experiment. AB - We use data from a large-scale experiment conducted in Indiana in 2009-2010 to examine the impact of two interim assessment programs (mCLASS and Acuity) across the mathematics and reading achievement distributions. Specifically, we focus on whether the use of interim assessments has a particularly strong effect on improving outcomes for low achievers. Quantile regression is used to estimate treatment effects across the entire achievement distribution (i.e., provide estimates in the lower, middle, or upper tails). Results indicate that in Grades 3 to 8 (particularly third, fifth, and sixth) lower achievers seem to benefit more from interim assessments than higher achieving students. PMID- 29795880 TI - Testing the Difference of Correlated Agreement Coefficients for Statistical Significance. AB - This article addresses the problem of testing the difference between two correlated agreement coefficients for statistical significance. A number of authors have proposed methods for testing the difference between two correlated kappa coefficients, which require either the use of resampling methods or the use of advanced statistical modeling techniques. In this article, we propose a technique similar to the classical pairwise t test for means, which is based on a large-sample linear approximation of the agreement coefficient. We illustrate the use of this technique with several known agreement coefficients including Cohen's kappa, Gwet's AC1, Fleiss's generalized kappa, Conger's generalized kappa, Krippendorff's alpha, and the Brenann-Prediger coefficient. The proposed method is very flexible, can accommodate several types of correlation structures between coefficients, and requires neither advanced statistical modeling skills nor considerable computer programming experience. The validity of this method is tested with a Monte Carlo simulation. PMID- 29795881 TI - Assessing Validity of Measurement in Learning Disabilities Using Hierarchical Generalized Linear Modeling: The Roles of Anxiety and Motivation. AB - The purpose of the present studies was to test the hypothesis that the psychometric characteristics of ability scales may be significantly distorted if one accounts for emotional factors during test taking. Specifically, the present studies evaluate the effects of anxiety and motivation on the item difficulties of the Rasch model. In Study 1, the validity of a reading comprehension scale was evaluated using the Rasch model with 60 students with learning disabilities (LD). Item parameters were retested for the presence of anxiety and results indicated that the scale was substantially more difficult in its presence. Study 2 replicated the findings of Study 1 using maladaptive motivation and extended with inclusion of adaptive motivational variables in order to reverse the effect. Results using students with and without LD indicated that the difficulty levels of the scale was lower for students with LD, in the presence of positive motivation, compared with a typical student group. Study 3 extended the dichotomous hierarchical generalized linear model with polytomous data. The measures of an ability test were adjusted for the presence of anxiety and results indicated that differential item functioning was observed at both the global level and the most difficult ability item. It is concluded that the difficulty levels of a scale are heavily influenced by situational factors during testing, such as students' entry levels of motivation and affect. PMID- 29795882 TI - Rasch Model Parameter Estimation in the Presence of a Nonnormal Latent Trait Using a Nonparametric Bayesian Approach. AB - Standard approaches for estimating item response theory (IRT) model parameters generally work under the assumption that the latent trait being measured by a set of items follows the normal distribution. Estimation of IRT parameters in the presence of nonnormal latent traits has been shown to generate biased person and item parameter estimates. A number of methods, including Ramsay curve item response theory, have been developed to reduce such bias, and have been shown to work well for relatively large samples and long assessments. An alternative approach to the nonnormal latent trait and IRT parameter estimation problem, nonparametric Bayesian estimation approach, has recently been introduced into the literature. Very early work with this method has shown that it could be an excellent option for use when fitting the Rasch model when assumptions cannot be made about the distribution of the model parameters. The current simulation study was designed to extend research in this area by expanding the simulation conditions under which it is examined and to compare the nonparametric Bayesian estimation approach to the Ramsay curve item response theory, marginal maximum likelihood, maximum a posteriori, and the Bayesian Markov chain Monte Carlo estimation method. Results of the current study support that the nonparametric Bayesian estimation approach may be a preferred option when fitting a Rasch model in the presence of nonnormal latent traits and item difficulties, as it proved to be most accurate in virtually all scenarios that were simulated in this study. PMID- 29795883 TI - Exploring Rating Quality in Rater-Mediated Assessments Using Mokken Scale Analysis. AB - Mokken scale analysis is a probabilistic nonparametric approach that offers statistical and graphical tools for evaluating the quality of social science measurement without placing potentially inappropriate restrictions on the structure of a data set. In particular, Mokken scaling provides a useful method for evaluating important measurement properties, such as invariance, in contexts where response processes are not well understood. Because rater-mediated assessments involve complex interactions among many variables, including assessment contexts, student artifacts, rubrics, individual rater characteristics, and others, rater-assigned scores are suitable candidates for Mokken scale analysis. The purposes of this study are to describe a suite of indices that can be used to explore the psychometric quality of data from rater mediated assessments and to illustrate the substantive interpretation of Mokken based statistics and displays in this context. Techniques that are commonly used in polytomous applications of Mokken scaling are adapted for use with rater mediated assessments, with a focus on the substantive interpretation related to individual raters. Overall, the findings suggest that indices of rater monotonicity, rater scalability, and invariant rater ordering based on Mokken scaling provide diagnostic information at the level of individual raters related to the requirements for invariant measurement. These Mokken-based indices serve as an additional suite of diagnostic tools for exploring the quality of data from rater-mediated assessments that can supplement rating quality indices based on parametric models. PMID- 29795884 TI - Georg Rasch and Benjamin Wright's Struggle With the Unidimensional Polytomous Model With Sufficient Statistics. AB - This article reproduces correspondence between Georg Rasch of The University of Copenhagen and Benjamin Wright of The University of Chicago in the period from January 1966 to July 1967. This correspondence reveals their struggle to operationalize a unidimensional measurement model with sufficient statistics for responses in a set of ordered categories. The article then explains the original approach taken by Rasch, Wright, and Andersen, and then how, from a different tack originating in 1961 and culminating in 1978, three distinct stages of development led to the current relatively simple and elegant form of the model. The article shows that over this period of almost two decades, the demand for sufficiency of a unidimensional parameter of the object of measurement, which enabled the separation of this parameter from the parameter of the instrument, drove the theoretical development of the model. PMID- 29795885 TI - Question Order Affects the Measurement of Bullying Victimization Among Middle School Students. AB - Bullying among youth is recognized as a serious student problem, especially in middle school. The most common approach to measuring bullying is through student self-report surveys that ask questions about different types of bullying victimization. Although prior studies have shown that question-order effects may influence participant responses, no study has examined these effects with middle school students. A randomized experiment (n = 5,951 middle school students) testing the question-order effect found that changing the sequence of questions can result in 45% higher prevalence rates. These findings raise questions about the accuracy of several widely used bullying surveys. PMID- 29795887 TI - Measurement Error Correction Formula for Cluster-Level Group Differences in Cluster Randomized and Observational Studies. AB - Multilevel modeling (MLM) is frequently used to detect cluster-level group differences in cluster randomized trial and observational studies. Group differences on the outcomes (posttest scores) are detected by controlling for the covariate (pretest scores) as a proxy variable for unobserved factors that predict future attributes. The pretest and posttest scores that are most often used in MLM are total scores. In prior research, there have been concerns regarding measurement error in the use of total scores in using MLM. In this article, using ordinary least squares and an attenuation formula, we derive the measurement error correction formula for cluster-level group difference estimates from MLM in the presence of measurement error in the outcome, the covariate, or both. Examples are provided to illustrate the correction formula in cluster randomized and observational studies using between-cluster reliability coefficients recently developed. PMID- 29795886 TI - Hypothesis Testing Using Factor Score Regression: A Comparison of Four Methods. AB - In this article, an overview is given of four methods to perform factor score regression (FSR), namely regression FSR, Bartlett FSR, the bias avoiding method of Skrondal and Laake, and the bias correcting method of Croon. The bias correcting method is extended to include a reliable standard error. The four methods are compared with each other and with structural equation modeling (SEM) by using analytic calculations and two Monte Carlo simulation studies to examine their finite sample characteristics. Several performance criteria are used, such as the bias using the unstandardized and standardized parameterization, efficiency, mean square error, standard error bias, type I error rate, and power. The results show that the bias correcting method, with the newly developed standard error, is the only suitable alternative for SEM. While it has a higher standard error bias than SEM, it has a comparable bias, efficiency, mean square error, power, and type I error rate. PMID- 29795888 TI - Differences in Reaction to Immediate Feedback and Opportunity to Revise Answers for Multiple-Choice and Open-Ended Questions. AB - There are many reasons to believe that open-ended (OE) and multiple-choice (MC) items elicit different cognitive demands of students. However, empirical evidence that supports this view is lacking. In this study, we investigated the reactions of test takers to an interactive assessment with immediate feedback and answer revision opportunities for the two types of items. Eighth-grade students solved mathematics problems, both MC and OE, with standard instructions and feedback-and revision opportunities. An analysis of scores based on revised answers in feedback mode revealed gains in measurement precision for OE items but not for MC items. These results are explained through the concept of effortful engagement the OE format encourages more mindful engagement with the items in interactive mode. This interpretation is supported by analyses of response times and test takers' reports. PMID- 29795889 TI - The Effects of Including Observed Means or Latent Means as Covariates in Multilevel Models for Cluster Randomized Trials. AB - We investigated methods of including covariates in two-level models for cluster randomized trials to increase power to detect the treatment effect. We compared multilevel models that included either an observed cluster mean or a latent cluster mean as a covariate, as well as the effect of including Level 1 deviation scores in the model. A Monte Carlo simulation study was performed manipulating effect sizes, cluster sizes, number of clusters, intraclass correlation of the outcome, patterns of missing data, and the squared correlations between Level 1 and Level 2 covariates and the outcome. We found no substantial difference between models with observed means or latent means with respect to convergence, Type I error rates, coverage, and bias. However, coverage could fall outside of acceptable limits if a latent mean is included as a covariate when cluster sizes are small. In terms of statistical power, models with observed means performed similarly to models with latent means, but better when cluster sizes were small. A demonstration is provided using data from a study of the Tools for Getting Along intervention. PMID- 29795890 TI - The Impact of Ignoring the Level of Nesting Structure in Nonparametric Multilevel Latent Class Models. AB - The multilevel latent class model (MLCM) is a multilevel extension of a latent class model (LCM) that is used to analyze nested structure data structure. The nonparametric version of an MLCM assumes a discrete latent variable at a higher level nesting structure to account for the dependency among observations nested within a higher-level unit. In the present study, a simulation study was conducted to investigate the impact of ignoring the higher-level nesting structure. Three criteria-the model selection accuracy, the classification quality, and the parameter estimation accuracy-were used to evaluate the impact of ignoring the nested data structure. The results of the simulation study showed that ignoring higher-level nesting structure in an MLCM resulted in the poor performance of the Bayesian information criterion to recover the true latent structure, the inaccurate classification of individuals into latent classes, and the inflation of standard errors for parameter estimates, while the parameter estimates were not biased. This article concludes with remarks on ignoring the nested structure in nonparametric MLCMs, as well as recommendations for applied researchers when LCM is used for data collected from a multilevel nested structure. PMID- 29795892 TI - Do Two or More Multicomponent Instruments Measure the Same Construct? Testing Construct Congruence Using Latent Variable Modeling. AB - A latent variable modeling procedure is discussed that can be used to test if two or more homogeneous multicomponent instruments with distinct components are measuring the same underlying construct. The method is widely applicable in scale construction and development research and can also be of special interest in construct validation studies. The approach can be readily utilized in empirical settings with observed measure nonnormality and/or incomplete data sets. The procedure is based on testing model nesting restrictions, and it can be similarly employed to examine the collapsibility of latent variables evaluated by multidimensional measuring instruments. The outlined method is illustrated with two data examples. PMID- 29795891 TI - Different Approaches to Covariate Inclusion in the Mixture Rasch Model. AB - The present study investigates different approaches to adding covariates and the impact in fitting mixture item response theory models. Mixture item response theory models serve as an important methodology for tackling several psychometric issues in test development, including the detection of latent differential item functioning. A Monte Carlo simulation study is conducted in which data generated according to a two-class mixture Rasch model with both dichotomous and continuous covariates are fitted to several mixture Rasch models with misspecified covariates to examine the effects of covariate inclusion on model parameter estimation. In addition, both complete response data and incomplete response data with different types of missingness are considered in the present study in order to simulate practical assessment settings. Parameter estimation is carried out within a Bayesian framework vis-a-vis Markov chain Monte Carlo algorithms. PMID- 29795893 TI - Survey Satisficing Inflates Reliability and Validity Measures: An Experimental Comparison of College and Amazon Mechanical Turk Samples. AB - This study examined the predictors and psychometric outcomes of survey satisficing, wherein respondents provide quick, "good enough" answers (satisficing) rather than carefully considered answers (optimizing). We administered surveys to university students and respondents-half of whom held college degrees-from a for-pay survey website, and we used an experimental method to randomly assign the participants to survey formats, which presumably differed in task difficulty. Based on satisficing theory, we predicted that ability, motivation, and task difficulty would predict satisficing behavior and that satisficing would artificially inflate internal consistency reliability and both convergent and discriminant validity correlations. Indeed, results indicated effects for task difficulty and motivation in predicting survey satisficing, and satisficing in the first part of the study was associated with improved internal consistency reliability and convergent validity but also worse discriminant validity in the second part of the study. Implications for research designs and improvements are discussed. PMID- 29795894 TI - Extracting Spurious Latent Classes in Growth Mixture Modeling With Nonnormal Errors. AB - Growth mixture modeling is generally used for two purposes: (1) to identify mixtures of normal subgroups and (2) to approximate oddly shaped distributions by a mixture of normal components. Often in applied research this methodology is applied to both of these situations indistinctly: using the same fit statistics and likelihood ratio tests. This can lead to the overextraction of latent classes and the attribution of substantive meaning to these spurious classes. The goals of this study are (1) to explore the performance of the Bayesian information criterion, sample-adjusted BIC, and bootstrap likelihood ratio test in growth mixture modeling analysis with nonnormal distributed outcome variables and (2) to examine the effects of nonnormal time invariant covariates in the estimation of the number of latent classes when outcome variables are normally distributed. For both of these goals, we will include nonnormal conditions not considered previously in the literature. Two simulation studies were conducted. Results show that spurious classes may be selected and optimal solutions obtained in the data analysis when the population departs from normality even when the nonnormality is only present in time invariant covariates. PMID- 29795895 TI - An Approach to Scoring and Equating Tests With Binary Items: Piloting With Large Scale Assessments. AB - This article describes an approach to test scoring, referred to as delta scoring (D-scoring), for tests with dichotomously scored items. The D-scoring uses information from item response theory (IRT) calibration to facilitate computations and interpretations in the context of large-scale assessments. The D score is computed from the examinee's response vector, which is weighted by the expected difficulties (not "easiness") of the test items. The expected difficulty of each item is obtained as an analytic function of its IRT parameters. The D scores are independent of the sample of test-takers as they are based on expected item difficulties. It is shown that the D-scale performs a good bit better than the IRT logit scale by criteria of scale intervalness. To equate D-scales, it is sufficient to rescale the item parameters, thus avoiding tedious and error-prone procedures of mapping test characteristic curves under the method of IRT true score equating, which is often used in the practice of large-scale testing. The proposed D-scaling proved promising under its current piloting with large-scale assessments and the hope is that it can efficiently complement IRT procedures in the practice of large-scale testing in the field of education and psychology. PMID- 29795896 TI - Reliability and Model Fit. AB - The purpose of this article is to highlight the distinction between the reliability of test scores and the fit of psychometric measurement models, reminding readers why it is important to consider both when evaluating whether test scores are valid for a proposed interpretation and/or use. It is often the case that an investigator judges both the reliability of scores and the fit of a corresponding measurement model to be either acceptable or unacceptable for a given situation, but these are not the only possible outcomes. This article focuses on situations in which model fit is deemed acceptable, but reliability is not. Data were simulated based on the item characteristics of the PROMIS (Patient Reported Outcomes Measurement Information System) anxiety item bank and analyzed using methods from classical test theory, factor analysis, and item response theory. Analytic techniques from different psychometric traditions were used to illustrate that reliability and model fit are distinct, and that disagreement among indices of reliability and model fit may provide important information bearing on a particular validity argument, independent of the data analytic techniques chosen for a particular research application. We conclude by discussing the important information gleaned from the assessment of reliability and model fit. PMID- 29795897 TI - An Entropy-Based Measure for Assessing Fuzziness in Logistic Regression. AB - This article introduces an entropy-based measure of data-model fit that can be used to assess the quality of logistic regression models. Entropy has previously been used in mixture-modeling to quantify how well individuals are classified into latent classes. The current study proposes the use of entropy for logistic regression models to quantify the quality of classification and separation of group membership. Entropy complements preexisting measures of data-model fit and provides unique information not contained in other measures. Hypothetical data scenarios, an applied example, and Monte Carlo simulation results are used to demonstrate the application of entropy in logistic regression. Entropy should be used in conjunction with other measures of data-model fit to assess how well logistic regression models classify cases into observed categories. PMID- 29795898 TI - Evaluating Rater Accuracy in Rater-Mediated Assessments Using an Unfolding Model. AB - The number of performance assessments continues to increase around the world, and it is important to explore new methods for evaluating the quality of ratings obtained from raters. This study describes an unfolding model for examining rater accuracy. Accuracy is defined as the difference between observed and expert ratings. Dichotomous accuracy ratings (0 = inaccurate, 1 = accurate) are unfolded into three latent categories: inaccurate below expert ratings, accurate ratings, and inaccurate above expert ratings. The hyperbolic cosine model (HCM) is used to examine dichotomous accuracy ratings from a statewide writing assessment. This study suggests that HCM is a promising approach for examining rater accuracy, and that the HCM can provide a useful interpretive framework for evaluating the quality of ratings obtained within the context of rater-mediated assessments. PMID- 29795899 TI - Evaluation of Measurement Instrument Criterion Validity in Finite Mixture Settings. AB - A method for evaluating the validity of multicomponent measurement instruments in heterogeneous populations is discussed. The procedure can be used for point and interval estimation of criterion validity of linear composites in populations representing mixtures of an unknown number of latent classes. The approach permits also the evaluation of between-class validity differences as well as within-class validity coefficients. The method can similarly be used with known class membership when distinct populations are investigated, their number is known beforehand and membership in them is observed for the studied subjects, as well as in settings where only the number of latent classes is known. The discussed procedure is illustrated with numerical data. PMID- 29795900 TI - Effort in Low-Stakes Assessments: What Does It Take to Perform as Well as in a High-Stakes Setting? AB - Performance of students in low-stakes testing situations has been a concern and focus of recent research. However, researchers who have examined the effect of stakes on performance have not been able to compare low-stakes performance to truly high-stakes performance of the same students. Results of such a comparison are reported in this article. GRE test takers volunteered to take an additional low-stakes test, of either verbal or quantitative reasoning as part of a research study immediately following their operational high-stakes test. Analyses of performance under the high- and low-stakes situations revealed that the level of effort in the low-stakes situation (as measured by the amount of time on task) strongly predicted the stakes effect on performance (difference between test scores in low- and high-stakes situations). Moreover, the stakes effect virtually disappeared for participants who spent at least one-third of the allotted time in the low-stakes situation. For this group of test takers (more than 80% of the total sample), the correlations between the low- and high-stakes scores approached the upper bound possible considering the reliability of the test. PMID- 29795901 TI - The Impact of Intraclass Correlation on the Effectiveness of Level-Specific Fit Indices in Multilevel Structural Equation Modeling: A Monte Carlo Study. AB - Several researchers have recommended that level-specific fit indices should be applied to detect the lack of model fit at any level in multilevel structural equation models. Although we concur with their view, we note that these studies did not sufficiently consider the impact of intraclass correlation (ICC) on the performance of level-specific fit indices. Our study proposed to fill this gap in the methodological literature. A Monte Carlo study was conducted to investigate the performance of (a) level-specific fit indices derived by a partially saturated model method (e.g., [Formula: see text] and [Formula: see text]) and (b) [Formula: see text] and [Formula: see text] in terms of their performance in multilevel structural equation models across varying ICCs. The design factors included intraclass correlation (ICC: ICC1 = 0.091 to ICC6 = 0.500), numbers of groups in between-level models (NG: 50, 100, 200, and 1,000), group size (GS: 30, 50, and 100), and type of misspecification (no misspecification, between-level misspecification, and within-level misspecification). Our simulation findings raise a concern regarding the performance of between-level-specific partial saturated fit indices in low ICC conditions: the performances of both [Formula: see text] and [Formula: see text] were more influenced by ICC compared with [Formula: see text] and SRMRB . However, when traditional cutoff values (RMSEA<= 0.06; CFI, TLI>= 0.95; SRMR<= 0.08) were applied, [Formula: see text] and [Formula: see text] were still able to detect misspecified between-level models even when ICC was as low as 0.091 (ICC1). On the other hand, both [Formula: see text] and [Formula: see text] were not recommended under low ICC conditions. PMID- 29795902 TI - Mountain or Molehill? A Simulation Study on the Impact of Response Styles. AB - Even though there is an increasing interest in response styles, the field lacks a systematic investigation of the bias that response styles potentially cause. Therefore, a simulation was carried out to study this phenomenon with a focus on applied settings (reliability, validity, scale scores). The influence of acquiescence and extreme response style was investigated, and independent variables were, for example, the number of reverse-keyed items. Data were generated from a multidimensional item response model. The results indicated that response styles may bias findings based on self-report data and that this bias may be substantial if the attribute of interest is correlated with response style. However, in the absence of such correlations, bias was generally very small, especially for extreme response style and if acquiescence was controlled for by reverse-keyed items. An empirical example was used to illustrate and validate the simulations. In summary, it is concluded that the threat of response styles may be smaller than feared. PMID- 29795903 TI - Three New Methods for Analysis of Answer Changes. AB - In a pioneering research article, Wollack and colleagues suggested the "erasure detection index" (EDI) to detect test tampering. The EDI can be used with or without a continuity correction and is assumed to follow the standard normal distribution under the null hypothesis of no test tampering. When used without a continuity correction, the EDI often has inflated Type I error rates. When used with a continuity correction, the EDI has satisfactory Type I error rates, but smaller power compared with the EDI without a continuity correction. This article suggests three methods for detecting test tampering that do not rely on the assumption of a standard normal distribution under the null hypothesis. It is demonstrated in a detailed simulation study that the performance of each suggested method is slightly better than that of the EDI. The EDI and the suggested methods were applied to a real data set. The suggested methods, although more computation intensive than the EDI, seem to be promising in detecting test tampering. PMID- 29795904 TI - Improving Measures via Examining the Behavior of Distractors in Multiple-Choice Tests: Assessment and Remediation. AB - The purpose of the present article was to illustrate, using an example from a national assessment, the value from analyzing the behavior of distractors in measures that engage the multiple-choice format. A secondary purpose of the present article was to illustrate four remedial actions that can potentially improve the measurement of the construct(s) under study. Participants were 2,248 individuals who took a national examination of chemistry. The behavior of the distractors was analyzed by modeling their behavior within the Rasch model. Potentially informative distractors were (a) further modeled using the partial credit model, (b) split onto separate items and retested for model fit and parsimony, (c) combined to form a "super" item or testlet, and (d) reexamined after deleting low-ability individuals who likely guessed on those informative, albeit erroneous, distractors. Results indicated that all but the item split strategies were associated with better model fit compared with the original model. The best fitted model, however, involved modeling and crediting informative distractors via the partial credit model or eliminating the responses of low-ability individuals who likely guessed on informative distractors. The implications, advantages, and disadvantages of modeling informative distractors for measurement purposes are discussed. PMID- 29795905 TI - A Monte Carlo Study of an Iterative Wald Test Procedure for DIF Analysis. AB - This study examined the performance of a proposed iterative Wald approach for detecting differential item functioning (DIF) between two groups when preknowledge of anchor items is absent. The iterative approach utilizes the Wald 2 approach to identify anchor items and then iteratively tests for DIF items with the Wald-1 approach. Monte Carlo simulation was conducted across several conditions including the number of response options, test length, sample size, percentage of DIF items, DIF effect size, and type of cumulative DIF. Results indicated that the iterative approach performed well for polytomous data in all conditions, with well-controlled Type I error rates and high power. For dichotomous data, the iterative approach also exhibited better control over Type I error rates than the Wald-2 approach without sacrificing the power in detecting DIF. However, inflated Type I error rates were found for the iterative approach in conditions with dichotomous data, noncompensatory DIF, large percentage of DIF items, and medium to large DIF effect sizes. Nevertheless, the Type I error rates were substantially less inflated in those conditions compared with the Wald-2 approach. PMID- 29795906 TI - Power Analysis for Models of Change in Cluster Randomized Designs. AB - Field experiments in education frequently assign entire groups such as schools to treatment or control conditions. These experiments incorporate sometimes a longitudinal component where for example students are followed over time to assess differences in the average rate of linear change, or rate of acceleration. In this study, we provide methods for power analysis in three-level polynomial change models for cluster randomized designs (i.e., treatment assigned to units at the third level). Power computations take into account clustering effects at the second and third levels, the number of measurement occasions, the impact of sample sizes at different levels (e.g., number of schools or students), and covariates effects. An illustrative example that shows how power is influenced by the number of measurement occasions, and sample sizes and covariates at the second or third levels is presented. PMID- 29795907 TI - Psychometric Consequences of Subpopulation Item Parameter Drift. AB - This study defines subpopulation item parameter drift (SIPD) as a change in item parameters over time that is dependent on subpopulations of examinees, and hypothesizes that the presence of SIPD in anchor items is associated with bias and/or lack of invariance in three psychometric outcomes. Results show that SIPD in anchor items is associated with a lack of invariance in dimensionality structure of an anchor test, a lack of invariance in scaling coefficients across subpopulations, and a lack of invariance in ability estimates. It is demonstrated that these effects go beyond what can be understood from item parameter drift or differential item functioning. PMID- 29795908 TI - On the Fallibility of Principal Components in Research. AB - The measurement error in principal components extracted from a set of fallible measures is discussed and evaluated. It is shown that as long as one or more measures in a given set of observed variables contains error of measurement, so also does any principal component obtained from the set. The error variance in any principal component is shown to be (a) bounded from below by the smallest error variance in a variable from the analyzed set and (b) bounded from above by the largest error variance in a variable from that set. In the case of a unidimensional set of analyzed measures, it is pointed out that the reliability and criterion validity of any principal component are bounded from above by these respective coefficients of the optimal linear combination with maximal reliability and criterion validity (for a criterion unrelated to the error terms in the individual measures). The discussed psychometric features of principal components are illustrated on a numerical data set. PMID- 29795909 TI - Testing the Difference Between Reliability Coefficients Alpha and Omega. AB - Reliable measurements are key to social science research. Multiple measures of reliability of the total score have been developed, including coefficient alpha, coefficient omega, the greatest lower bound reliability, and others. Among these, the coefficient alpha has been most widely used, and it is reported in nearly every study involving the measure of a construct through multiple items in social and behavioral research. However, it is known that coefficient alpha underestimates the true reliability unless the items are tau-equivalent, and coefficient omega is deemed as a practical alternative to coefficient alpha in estimating measurement reliability of the total score. However, many researchers noticed that the difference between alpha and omega is minor in applications. Since the observed differences in alpha and omega can be due to sampling errors, the purpose of the present study, therefore, is to propose a method to evaluate the difference of coefficient alpha ([Formula: see text]) and omega ([Formula: see text]) statistically. In particular, the current article develops a procedure to estimate the SE of ([Formula: see text]) and consequently the confidence interval (CI) for ([Formula: see text]). This procedure allows us to test whether the observed difference ([Formula: see text]) is due to sample error or [Formula: see text] is significantly greater than [Formula: see text]. The developed procedure is then applied to multiple real data sets from well-known scales to empirically verify the values of ([Formula: see text]) in practice. Results showed that in most of the comparisons the differences are significantly above zero but cases also exist where the CIs contain zero. An R program for calculating [Formula: see text], [Formula: see text], and the SE of ([Formula: see text]) is also included in the present study so that the developed procedure is easily accessible to applied researchers. PMID- 29795910 TI - Performing Inferential Statistics Prior to Data Collection. AB - Typically, in education and psychology research, the investigator collects data and subsequently performs descriptive and inferential statistics. For example, a researcher might compute group means and use the null hypothesis significance testing procedure to draw conclusions about the populations from which the groups were drawn. We propose an alternative inferential statistical procedure that is performed prior to data collection rather than afterwards. To use this procedure, the researcher specifies how close she or he desires the group means to be to their corresponding population means and how confident she or he wishes to be that this actually is so. We derive an equation that provides researchers with a way to determine the sample size needed to meet the specifications concerning closeness and confidence, regardless of the number of groups. PMID- 29795911 TI - The Impact of Q-Matrix Designs on Diagnostic Classification Accuracy in the Presence of Attribute Hierarchies. AB - There is an increasing demand for assessments that can provide more fine-grained information about examinees. In response to the demand, diagnostic measurement provides students with feedback on their strengths and weaknesses on specific skills by classifying them into mastery or nonmastery attribute categories. These attributes often form a hierarchical structure because student learning and development is a sequential process where many skills build on others. However, it remains to be seen if we can use information from the attribute structure and work that into the design of the diagnostic tests. The purpose of this study is to introduce three approaches of Q-matrix design and investigate their impact on classification results under different attribute structures. Results indicate that the adjacent approach provides higher accuracy in a shorter test length when compared with other Q-matrix design approaches. This study provides researchers and practitioners guidance on how to design the Q-matrix in diagnostic tests, which are in high demand from educators. PMID- 29795912 TI - Heuristic Constraint Management Methods in Multidimensional Adaptive Testing. AB - Although multidimensional adaptive testing (MAT) has been proven to be highly advantageous with regard to measurement efficiency when several highly correlated dimensions are measured, there are few operational assessments that use MAT. This may be due to issues of constraint management, which is more complex in MAT than it is in unidimensional adaptive testing. Very few studies have examined the performance of existing constraint management methods (CMMs) in MAT. The present article focuses on the effectiveness of two promising heuristic CMMs in MAT for varying levels of imposed constraints and for various correlations between the measured dimensions. Through a simulation study, the multidimensional maximum priority index (MMPI) and multidimensional weighted penalty model (MWPM), as an extension of the weighted penalty model, are examined with regard to measurement precision and constraint violations. The results show that both CMMs are capable of addressing complex constraints in MAT. However, measurement precision losses were found to differ between the MMPI and MWPM. While the MMPI appears to be more suitable for use in assessment situations involving few to a moderate number of constraints, the MWPM should be used when numerous constraints are involved. PMID- 29795913 TI - Comparative Analyses of MIRT Models and Software (BMIRT and flexMIRT). AB - Application of MIRT modeling procedures is dependent on the quality of parameter estimates provided by the estimation software and techniques used. This study investigated model parameter recovery of two popular MIRT packages, BMIRT and flexMIRT, under some common measurement conditions. These packages were specifically selected to investigate the model parameter recovery of three item parameter estimation techniques, namely, Bock-Aitkin EM (BA-EM), Markov chain Monte Carlo (MCMC), and Metropolis-Hastings Robbins-Monro (MH-RM) algorithms. The results demonstrated that all estimation techniques had similar root mean square error values when larger sample size and higher test length were used. Depending on the number of dimensions, sample size, and test length, each estimation technique exhibited some strengths and weaknesses. Overall, the BA-EM technique was found to have shorter estimation time with all test specifications. PMID- 29795914 TI - Mixture IRT Model With a Higher-Order Structure for Latent Traits. AB - Mixture item response theory (IRT) models have been suggested as an efficient method of detecting the different response patterns derived from latent classes when developing a test. In testing situations, multiple latent traits measured by a battery of tests can exhibit a higher-order structure, and mixtures of latent classes may occur on different orders and influence the item responses of examinees from different classes. This study aims to develop a new class of higher-order mixture IRT models by integrating mixture IRT models and higher order IRT models to address these practical concerns. The proposed higher-order mixture IRT models can accommodate both linear and nonlinear models for latent traits and incorporate diverse item response functions. The Rasch model was selected as the item response function, metric invariance was assumed in the first simulation study, and multiparameter IRT models without an assumption of metric invariance were used in the second simulation study. The results show that the parameters can be recovered fairly well using WinBUGS with Bayesian estimation. A larger sample size resulted in a better estimate of the model parameters, and a longer test length yielded better individual ability recovery and latent class membership recovery. The linear approach outperformed the nonlinear approach in the estimation of first-order latent traits, whereas the opposite was true for the estimation of the second-order latent trait. Additionally, imposing identical factor loadings between the second- and first order latent traits by fitting the mixture bifactor model resulted in biased estimates of the first-order latent traits and item parameters. Finally, two empirical analyses are provided as an example to illustrate the applications and implications of the new models. PMID- 29795915 TI - Comparing the Performance of Approaches for Testing the Homogeneity of Variance Assumption in One-Factor ANOVA Models. AB - Various tests to check the homogeneity of variance assumption have been proposed in the literature, yet there is no consensus as to their robustness when the assumption of normality does not hold. This simulation study evaluated the performance of 14 tests for the homogeneity of variance assumption in one-way ANOVA models in terms of Type I error control and statistical power. Seven factors were manipulated: number of groups, average number of observations per group, pattern of sample sizes in groups, pattern of population variances, maximum variance ratio, population distribution shape, and nominal alpha level for the test of variances. Overall, the Ramsey conditional, O'Brien, Brown Forsythe, Bootstrap Brown-Forsythe, and Levene with squared deviations tests maintained adequate Type I error control, performing better than the others across all the conditions. The power for each of these five tests was acceptable and the power differences were subtle. Guidelines for selecting a valid test for assessing the tenability of this critical assumption are provided based on average cell size. PMID- 29795916 TI - Adjacent-Categories Mokken Models for Rater-Mediated Assessments. AB - Molenaar extended Mokken's original probabilistic-nonparametric scaling models for use with polytomous data. These polytomous extensions of Mokken's original scaling procedure have facilitated the use of Mokken scale analysis as an approach to exploring fundamental measurement properties across a variety of domains in which polytomous ratings are used, including rater-mediated educational assessments. Because their underlying item step response functions (i.e., category response functions) are defined using cumulative probabilities, polytomous Mokken models can be classified as cumulative models based on the classifications of polytomous item response theory models proposed by several scholars. In order to permit a closer conceptual alignment with educational performance assessments, this study presents an adjacent-categories variation on the polytomous monotone homogeneity and double monotonicity models. Data from a large-scale rater-mediated writing assessment are used to illustrate the adjacent categories approach, and results are compared with the original formulations. Major findings suggest that the adjacent-categories models provide additional diagnostic information related to individual raters' use of rating scale categories that is not observed under the original formulation. Implications are discussed in terms of methods for evaluating rating quality. PMID- 29795917 TI - Comparing Between- and Within-Group Variances in a Two-Level Study: A Latent Variable Modeling Approach to Evaluating Their Relationship. AB - This note is concerned with examining the relationship between within-group and between-group variances in two-level nested designs. A latent variable modeling approach is outlined that permits point and interval estimation of their ratio and allows their comparison in a multilevel study. The procedure can also be used to test various hypotheses about the discrepancy between these two variances and assist with their relationship interpretability in empirical investigations. The method can also be utilized as an addendum to point and interval estimation of the popular intraclass correlation coefficient in hierarchical designs. The discussed approach is illustrated with a numerical example. PMID- 29795918 TI - Assessing Change in Latent Skills Across Time With Longitudinal Cognitive Diagnosis Modeling: An Evaluation of Model Performance. AB - Cognitive diagnosis models are diagnostic models used to classify respondents into homogenous groups based on multiple categorical latent variables representing the measured cognitive attributes. This study aims to present longitudinal models for cognitive diagnosis modeling, which can be applied to repeated measurements in order to monitor attribute stability of individuals and to account for respondent dependence. Models based on combining latent transition analysis modeling and the DINA and DINO cognitive diagnosis models were developed and then evaluated through a Monte Carlo simulation study. The study results indicate that the proposed models provide adequate convergence and correct classification rates. PMID- 29795919 TI - Influence of Context on Item Parameters in Forced-Choice Personality Assessments. AB - A fundamental assumption in computerized adaptive testing is that item parameters are invariant with respect to context-items surrounding the administered item. This assumption, however, may not hold in forced-choice (FC) assessments, where explicit comparisons are made between items included in the same block. We empirically examined the influence of context on item parameters by comparing parameter estimates from two FC instruments. The first instrument was composed of blocks of three items, whereas in the second, the context was manipulated by adding one item to each block, resulting in blocks of four. The item parameter estimates were highly similar. However, a small number of significant deviations were observed, confirming the importance of context when designing adaptive FC assessments. Two patterns of such deviations were identified, and methods to reduce their occurrences in an FC computerized adaptive testing setting were proposed. It was shown that with a small proportion of violations of the parameter invariance assumption, score estimation remained stable. PMID- 29795920 TI - Effect of Purification Procedures on DIF Analysis in IRTPRO. AB - Purification of the test has been a well-accepted procedure in enhancing the performance of tests for differential item functioning (DIF). As defined by Lord, purification requires reestimation of ability parameters after removing DIF items before conducting the final DIF analysis. IRTPRO 3 is a recently updated program for analyses in item response theory, with built-in DIF tests but not purification procedures. A simulation study was conducted to investigate the effect of two new methods of purification. The results suggested that one of the purification procedures showed significantly improved power and Type I error. The procedure, which can be cumbersome by hand, can be easily applied by practitioners by using the web-based program developed for this study. PMID- 29795921 TI - An examination of Alternative Multidimensional Scaling Techniques. AB - The purpose of this study is to compare alternative multidimensional scaling (MDS) methods for constraining the stimuli on the circumference of a circle and on the surface of a sphere. Specifically, the existing MDS-T method for plotting the stimuli on the circumference of a circle is applied, and its extension is proposed for constraining the stimuli on the surface of a sphere. The data analyzed come from previous research and concerns Maslach and Jackson's burnout syndrome and Holland's vocational personality types. The configurations for the same data on the circle and the sphere shared similarities but also had differences, that is, the general item-groupings were the same but most of the differences across the two methods resulted in more meaningful interpretations for the three-dimensional configuration. Furthermore, in most cases, items and/or scales could be better discriminated from each other on the sphere. PMID- 29795922 TI - Variability in the Results of Meta-Analysis as a Function of Comparing Effect Sizes Based on Scores From Noncomparable Measures: A Simulation Study. AB - Meta-analysis is a significant methodological advance that is increasingly important in research synthesis. Fundamental to meta-analysis is the presumption that effect sizes, such as the standardized mean difference (SMD), based on scores from different measures are comparable. It has been argued that population observed score SMDs based on scores from different measures A and B will be equal only if the conjunction of three conditions are met: construct equivalence (CE), equal reliabilities (ER), and the absence of differential test functioning (DTF) in all subpopulations of the combined populations of interest. It has also been speculated the results of a meta-analysis of SMDs might differ between circumstances in which the SMDs included in a meta-analysis are based on measures which all met the conjunction of these conditions and that in which the conjunction of these conditions is violated. No previous studies have tested this conjecture. This Monte Carlo study investigated this hypothesis. A population of studies comparing one of five hypothetical treatments with a placebo condition was simulated. The SMDs in these simulated studies were based on true scores from six hypothetical measures. The scores from some of these measures met the conjunction of CE, ER, and, the absence of DTF, while others failed to meet CE. Three meta-analyses were conducted using both fixed effects and random effects methods. The results suggested that the results of meta-analyses can vary to a practically significant degree when the SMDs were based on scores from measures failing to meet the CE condition. Implications for future research are considered. PMID- 29795923 TI - Perspectives on the Use of Null Hypothesis Statistical Testing. Part I: The Mighty Frames of Scientific and Statistical Inference. PMID- 29795924 TI - What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing. AB - We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical testing, the controversies in multiple regression, and multiplicity issues in statistics, we describe how these difficult issues should be handled based on our interpretation of the similarity principle. PMID- 29795925 TI - Tests of Statistical Significance Made Sound. AB - This article considers the nature and place of tests of statistical significance (ToSS) in science, with particular reference to psychology. Despite the enormous amount of attention given to this topic, psychology's understanding of ToSS remains deficient. The major problem stems from a widespread and uncritical acceptance of null hypothesis significance testing (NHST), which is an indefensible amalgam of ideas adapted from Fisher's thinking on the subject and from Neyman and Pearson's alternative account. To correct for the deficiencies of the hybrid, it is suggested that psychology avail itself of two important and more recent viewpoints on ToSS, namely the neo-Fisherian and the error statistical perspectives. The neo-Fisherian perspective endeavors to improve on Fisher's original account and rejects key elements of Neyman and Pearson's alternative. In contrast, the error-statistical perspective builds on the strengths of both statistical traditions. It is suggested that these more recent outlooks on ToSS are a definite improvement on NHST, especially the error statistical position. It is suggested that ToSS can play a useful, if limited, role in psychological research. At the end, some lessons learnt from the extensive debates about ToSS are presented. PMID- 29795926 TI - On Some Assumptions of the Null Hypothesis Statistical Testing. AB - Bayesian and classical statistical approaches are based on different types of logical principles. In order to avoid mistaken inferences and misguided interpretations, the practitioner must respect the inference rules embedded into each statistical method. Ignoring these principles leads to the paradoxical conclusions that the hypothesis [Formula: see text] could be less supported by the data than a more restrictive hypothesis such as [Formula: see text], where [Formula: see text] and [Formula: see text] are two population means. This article intends to discuss and explicit some important assumptions inherent to classical statistical models and null statistical hypotheses. Furthermore, the definition of the p-value and its limitations are analyzed. An alternative measure of evidence, the s-value, is discussed. This article presents the steps to compute s-values and, in order to illustrate the methods, some standard examples are analyzed and compared with p-values. The examples denunciate that p values, as opposed to s-values, fail to hold some logical relations. PMID- 29795927 TI - Three Insights from a Bayesian Interpretation of the One-Sided P Value. AB - P values have been critiqued on several grounds but remain entrenched as the dominant inferential method in the empirical sciences. In this article, we elaborate on the fact that in many statistical models, the one-sided P value has a direct Bayesian interpretation as the approximate posterior mass for values lower than zero. The connection between the one-sided P value and posterior probability mass reveals three insights: (1) P values can be interpreted as Bayesian tests of direction, to be used only when the null hypothesis is known from the outset to be false; (2) as a measure of evidence, P values are biased against a point null hypothesis; and (3) with N fixed and effect size variable, there is an approximately linear relation between P values and Bayesian point null hypothesis tests. PMID- 29795928 TI - An Unbiased Estimate of Global Interrater Agreement. AB - Assessing global interrater agreement is difficult as most published indices are affected by the presence of mixtures of agreements and disagreements. A previously proposed method was shown to be specifically sensitive to global agreement, excluding mixtures, but also negatively biased. Here, we propose two alternatives in an attempt to find what makes such methods so specific. The first method, RB , is found to be unbiased while at the same time rejecting mixtures, is detecting agreement with good power and is little affected by unequal category prevalence as soon as there are more than two categories. PMID- 29795929 TI - Do Adaptive Representations of the Item-Position Effect in APM Improve Model Fit? A Simulation Study. AB - The item-position effect describes how an item's position within a test, that is, the number of previous completed items, affects the response to this item. Previously, this effect was represented by constraints reflecting simple courses, for example, a linear increase. Due to the inflexibility of these representations our aim was to examine whether adapted representations are more appropriate than the existing ones. Models of confirmatory factor analysis were used for testing the different representations. Analyses were conducted by means of simulated data that followed the covariance pattern of Raven's Advanced Progressive Matrices (APM) items. Since the item-position effect has been demonstrated repeatedly for the APM, it is a very suitable measure for our investigations. Results revealed no remarkable improvement by using an adapted representation. Possible reasons causing these results are discussed. PMID- 29795930 TI - Investigating Approaches to Estimating Covariate Effects in Growth Mixture Modeling: A Simulation Study. AB - Researchers continue to be interested in efficient, accurate methods of estimating coefficients of covariates in mixture modeling. Including covariates related to the latent class analysis not only may improve the ability of the mixture model to clearly differentiate between subjects but also makes interpretation of latent group membership more meaningful. Very few studies have been conducted that compare the performance of various approaches to estimating covariate effects in mixture modeling, and fewer yet have considered more complicated models such as growth mixture models where the latent class variable is more difficult to identify. A Monte Carlo simulation was conducted to investigate the performance of four estimation approaches: (1) the conventional three-step approach, (2) the one-step maximum likelihood (ML) approach, (3) the pseudo class (PC) approach, and (4) the three-step ML approach in terms of their ability to recover covariate effects in the logistic regression class membership model within a growth mixture modeling framework. Results showed that when class separation was large, the one-step ML approach and the three-step ML approach displayed much less biased covariate effect estimates than either the conventional three-step approach or the PC approach. When class separation was poor, estimation of the relation between the dichotomous covariate and latent class variable was severely affected when the new three-step ML approach was used. PMID- 29795931 TI - ATS-PD: An Adaptive Testing System for Psychological Disorders. AB - The clinical assessment of mental disorders can be a time-consuming and error prone procedure, consisting of a sequence of diagnostic hypothesis formulation and testing aimed at restricting the set of plausible diagnoses for the patient. In this article, we propose a novel computerized system for the adaptive testing of psychological disorders. The proposed system combines a mathematical representation of psychological disorders, known as the "formal psychological assessment," with an algorithm designed for the adaptive assessment of an individual's knowledge. The assessment algorithm is extended and adapted to the new application domain. Testing the system on a real sample of 4,324 healthy individuals, screened for obsessive-compulsive disorder, we demonstrate the system's ability to support clinical testing, both by identifying the correct critical areas for each individual and by reducing the number of posed questions with respect to a standard written questionnaire. PMID- 29795932 TI - Perspectives on the Use of Null Hypothesis Statistical Testing. Part III: The Various Nuts and Bolts of Statistical and Hypothesis Testing. PMID- 29795933 TI - What Are the Odds? Modern Relevance and Bayes Factor Solutions for MacAlister's Problem From the 1881 Educational Times. AB - In 1881, Donald MacAlister posed a problem in the Educational Times that remains relevant today. The problem centers on the statistical evidence for the effectiveness of a treatment based on a comparison between two proportions. A brief historical sketch is followed by a discussion of two default Bayesian solutions, one based on a one-sided test between independent rates, and one on a one-sided test between dependent rates. We demonstrate the current-day relevance of MacAlister's original question with a modern-day example about the effectiveness of an educational program. PMID- 29795934 TI - Using the Coefficient of Confidence to Make the Philosophical Switch From A Posteriori to A Priori Inferential Statistics. AB - There has been much controversy over the null hypothesis significance testing procedure, with much of the criticism centered on the problem of inverse inference. Specifically, p gives the probability of the finding (or one more extreme) given the null hypothesis, whereas the null hypothesis significance testing procedure involves drawing a conclusion about the null hypothesis given the finding. Many critics have called for null hypothesis significance tests to be replaced with confidence intervals. However, confidence intervals also suffer from a version of the inverse inference problem. The only known solution to the inverse inference problem is to use the famous theorem by Bayes, but this involves commitments that many researchers are not willing to make. However, it is possible to ask a useful question for which inverse inference is not a problem and that leads to the computation of the coefficient of confidence. In turn, and much more important, using the coefficient of confidence implies the desirability of switching from the current emphasis on a posteriori inferential statistics to an emphasis on a priori inferential statistics. PMID- 29795935 TI - Observation-Oriented Modeling: Going Beyond "Is It All a Matter of Chance"? AB - An alternative to null hypothesis significance testing is presented and discussed. This approach, referred to as observation-oriented modeling, is centered on model building in an effort to explicate the structures and processes believed to generate a set of observations. In terms of analysis, this novel approach complements traditional methods based on means, variances, and covariances with methods of pattern detection and analysis. Using data from a previously published study by Shoda et al., the basic tenets and methods of observation-oriented modeling are demonstrated and compared with traditional methods, particularly with regard to null hypothesis significance testing. PMID- 29795936 TI - Neuroimaging Research: From Null-Hypothesis Falsification to Out-of-Sample Generalization. AB - Brain-imaging technology has boosted the quantification of neurobiological phenomena underlying human mental operations and their disturbances. Since its inception, drawing inference on neurophysiological effects hinged on classical statistical methods, especially, the general linear model. The tens of thousands of variables per brain scan were routinely tackled by independent statistical tests on each voxel. This circumvented the curse of dimensionality in exchange for neurobiologically imperfect observation units, a challenging multiple comparisons problem, and limited scaling to currently growing data repositories. Yet, the always bigger information granularity of neuroimaging data repositories has lunched a rapidly increasing adoption of statistical learning algorithms. These scale naturally to high-dimensional data, extract models from data rather than prespecifying them, and are empirically evaluated for extrapolation to unseen data. The present article portrays commonalities and differences between long-standing classical inference and upcoming generalization inference relevant for conducting neuroimaging research. PMID- 29795937 TI - Three Strategies for the Critical Use of Statistical Methods in Psychological Research. AB - We present three strategies to replace the null hypothesis statistical significance testing approach in psychological research: (1) visual representation of cognitive processes and predictions, (2) visual representation of data distributions and choice of the appropriate distribution for analysis, and (3) model comparison. The three strategies have been proposed earlier, so we do not claim originality. Here we propose to combine the three strategies and use them not only as analytical and reporting tools but also to guide the design of research. The first strategy involves a visual representation of the cognitive processes involved in solving the task at hand in the form of a theory or model together with a representation of a pattern of predictions for each condition. The second approach is the GAMLSS approach, which consists of providing a visual representation of distributions to fit the data, and choosing the best distribution that fits the raw data for further analyses. The third strategy is the model comparison approach, which compares the model of the researcher with alternative models. We present a worked example in the field of reasoning, in which we follow the three strategies. PMID- 29795938 TI - The Effect of Rating Unfamiliar Items on Angoff Passing Scores. AB - The Angoff standard setting method relies on content experts to review exam items and make judgments about the performance of the minimally proficient examinee. Unfortunately, at times content experts may have gaps in their understanding of specific exam content. These gaps are particularly likely to occur when the content domain is broad and/or highly technical, or when non-expert stakeholders are included in a standard setting panel (e.g., parents, administrators, or union representatives). When judges lack expertise regarding specific exam content, the ratings associated with those items may be bias. This study attempts to illustrate the impact of rating unfamiliar items on Angoff passing scores. The study presents a comparison of Angoff ratings for typical items with those identified by judges as containing unfamiliar content. The results indicate that judges tend to perceive unfamiliar items as being artificially difficult resulting in systematically lower Angoff ratings. The results suggest that when judges are forced to rate unfamiliar items, the validity of the resulting classification decision may be jeopardized. PMID- 29795939 TI - Estimating True Student Growth Percentile Distributions Using Latent Regression Multidimensional IRT Models. AB - Student Growth Percentiles (SGPs) increasingly are being used in the United States for inferences about student achievement growth and educator effectiveness. Emerging research has indicated that SGPs estimated from observed test scores have large measurement errors. As such, little is known about "true" SGPs, which are defined in terms of nonlinear functions of latent achievement attributes for individual students and their distributions across students. We develop a novel framework using latent regression multidimensional item response theory models to study distributional properties of true SGPs. We apply these methods to several cohorts of longitudinal item response data from more than 330,000 students in a large urban metropolitan area to provide new empirical information about true SGPs. We find that true SGPs are correlated 0.3 to 0.5 across mathematics and English language arts, and that they have nontrivial relationships with individual student characteristics, particularly student race/ethnicity and absenteeism. We evaluate the potential of using these relationships to improve the accuracy of SGPs estimated from observed test scores, finding that accuracy gains even under optimal circumstances are modest. We also consider the properties of SGPs averaged to the teacher level, widely used for teacher evaluations. We find that average true SGPs for individual teachers vary substantially as a function of the characteristics of the students they teach. We discuss implications of our findings for the estimation and interpretation of SGPs at both the individual and aggregate levels. PMID- 29795940 TI - Using a Multidimensional IRT Framework to Better Understand Differential Item Functioning (DIF): A Tale of Three DIF Detection Procedures. AB - The theoretical reason for the presence of differential item functioning (DIF) is that data are multidimensional and two groups of examinees differ in their underlying ability distribution for the secondary dimension(s). Therefore, the purpose of this study was to determine how much the secondary ability distributions must differ before DIF is detected. Two-dimensional binary data sets were simulated using a compensatory multidimensional item response theory (MIRT) model, incrementally varying the mean difference on the second dimension between reference and focal group examinees while systematically increasing the correlation between dimensions. Three different DIF detection procedures were used to test for DIF: (1) SIBTEST, (2) Mantel-Haenszel, and (3) logistic regression. Results indicated that even with a very small mean difference on the secondary dimension, smaller than typically considered in previous research, DIF will be detected. Additional analyses indicated that even with the smallest mean difference considered in this study, 0.25, statistically significant differences will almost always be found between reference and focal group examinees on subtest scores consisting of items measuring the secondary dimension. PMID- 29795941 TI - Data Integration Approaches to Longitudinal Growth Modeling. AB - Synthesizing results from multiple studies is a daunting task during which researchers must tackle a variety of challenges. The task is even more demanding when studying developmental processes longitudinally and when different instruments are used to measure constructs. Data integration methodology is an emerging field that enables researchers to pool data drawn from multiple existing studies. To date, these methods are not commonly utilized in the social and behavioral sciences, even though they can be very useful for studying various complex developmental processes. This article illustrates the use of two data integration methods, the data fusion and the parallel analysis approaches. The illustration makes use of six longitudinal studies of mathematics ability in children with a goal of examining individual changes in mathematics ability and determining differences in the trajectories based on sex and socioeconomic status. The studies vary in their assessment of mathematics ability and in the timing and number of measurement occasions. The advantages of using a data fusion approach, which can allow for the fitting of more complex growth models that might not otherwise have been possible to fit in a single data set, are emphasized. The article concludes with a discussion of the limitations and benefits of these approaches for research synthesis. PMID- 29795942 TI - Correcting Model Fit Criteria for Small Sample Latent Growth Models With Incomplete Data. AB - To date, small sample problems with latent growth models (LGMs) have not received the amount of attention in the literature as related mixed-effect models (MEMs). Although many models can be interchangeably framed as a LGM or a MEM, LGMs uniquely provide criteria to assess global data-model fit. However, previous studies have demonstrated poor small sample performance of these global data model fit criteria and three post hoc small sample corrections have been proposed and shown to perform well with complete data. However, these corrections use sample size in their computation-whose value is unclear when missing data are accommodated with full information maximum likelihood, as is common with LGMs. A simulation is provided to demonstrate the inadequacy of these small sample corrections in the near ubiquitous situation in growth modeling where data are incomplete. Then, a missing data correction for the small sample correction equations is proposed and shown through a simulation study to perform well in various conditions found in practice. An applied developmental psychology example is then provided to demonstrate how disregarding missing data in small sample correction equations can greatly affect assessment of global data-model fit. PMID- 29795943 TI - Kappa and Rater Accuracy: Paradigms and Parameters. AB - Drawing parallels to classical test theory, this article clarifies the difference between rater accuracy and reliability and demonstrates how category marginal frequencies affect rater agreement and Cohen's kappa (kappa). Category assignment paradigms are developed: comparing raters to a standard (index) versus comparing two raters to one another (concordance), using both nonstochastic and stochastic category membership. Using a probability model to express category assignments in terms of rater accuracy and random error, it is shown that observed agreement (Po) depends only on rater accuracy and number of categories; however, expected agreement (Pe) and kappa depend additionally on category frequencies. Moreover, category frequencies affect Pe and kappa solely through the variance of the category proportions, regardless of the specific frequencies underlying the variance. Paradoxically, some judgment paradigms involving stochastic categories are shown to yield higher kappa values than their nonstochastic counterparts. Using the stated probability model, assignments to categories were generated for 552 combinations of paradigms, rater and category parameters, category frequencies, and number of stimuli. Observed means and standard errors for Po, Pe, and kappa were fully consistent with theory expectations. Guidelines for interpretation of rater accuracy and reliability are offered, along with a discussion of alternatives to the basic model. PMID- 29795944 TI - A Reformulated Correlated Trait-Correlated Method Model for Multitrait Multimethod Data Effectively Increases Convergence and Admissibility Rates. AB - The correlated trait-correlated method (CTCM) model for the analysis of multitrait-multimethod (MTMM) data is known to suffer convergence and admissibility (C&A) problems. We describe a little known and seldom applied reparameterized version of this model (CTCM-R) based on Rindskopf's reparameterization of the simpler confirmatory factor analysis model. In a Monte Carlo study, we compare the CTCM, CTCM-R, and the correlated trait-correlated uniqueness (CTCU) models in terms of C&A, model fit, and parameter estimation bias. The CTCM-R model largely avoided C&A problems associated with the more traditional CTCM model, producing C&A solutions nearly as often as the CTCU model, but also avoiding parameter estimation biases known to plague the CTCU model. As such, the CTCM-R model is an attractive alternative for the analysis of MTMM data. PMID- 29795945 TI - Large Sample Confidence Intervals for Item Response Theory Reliability Coefficients. AB - In applications of item response theory (IRT), an estimate of the reliability of the ability estimates or sum scores is often reported. However, analytical expressions for the standard errors of the estimators of the reliability coefficients are not available in the literature and therefore the variability associated with the estimated reliability is typically not reported. In this study, the asymptotic variances of the IRT marginal and test reliability coefficient estimators are derived for dichotomous and polytomous IRT models assuming an underlying asymptotically normally distributed item parameter estimator. The results are used to construct confidence intervals for the reliability coefficients. Simulations are presented which show that the confidence intervals for the test reliability coefficient have good coverage properties in finite samples under a variety of settings with the generalized partial credit model and the three-parameter logistic model. Meanwhile, it is shown that the estimator of the marginal reliability coefficient has finite sample bias resulting in confidence intervals that do not attain the nominal level for small sample sizes but that the bias tends to zero as the sample size increases. PMID- 29795946 TI - Is the Factor Observed in Investigations on the Item-Position Effect Actually the Difficulty Factor? AB - In confirmatory factor analysis quite similar models of measurement serve the detection of the difficulty factor and the factor due to the item-position effect. The item-position effect refers to the increasing dependency among the responses to successively presented items of a test whereas the difficulty factor is ascribed to the wide range of item difficulties. The similarity of the models of measurement hampers the dissociation of these factors. Since the item-position effect should theoretically be independent of the item difficulties, the statistical ex post manipulation of the difficulties should enable the discrimination of the two types of factors. This method was investigated in two studies. In the first study, Advanced Progressive Matrices (APM) data of 300 participants were investigated. As expected, the factor thought to be due to the item-position effect was observed. In the second study, using data simulated to show the major characteristics of the APM data, the wide range of items with various difficulties was set to zero to reduce the likelihood of detecting the difficulty factor. Despite this reduction, however, the factor now identified as item-position factor, was observed in virtually all simulated datasets. PMID- 29795947 TI - Modifying Spearman's Attenuation Equation to Yield Partial Corrections for Measurement Error-With Application to Sample Size Calculations. AB - Spearman's correction for attenuation (measurement error) corrects a correlation coefficient for measurement errors in either-or-both of two variables, and follows from the assumptions of classical test theory. Spearman's equation removes all measurement error from a correlation coefficient which translates into "increasing the reliability of either-or-both of two variables to 1.0." In this inquiry, Spearman's correction is modified to allow partial removal of measurement error from either-or-both of two variables being correlated. The practical utility of this partial correction is demonstrated in its use to explore increasing the power of statistical tests by increasing sample size versus increasing the reliability of the dependent variable for an experiment. Other applied uses are mentioned. PMID- 29795948 TI - The Impact of Validity Screening on Associations Between Self-Reports of Bullying Victimization and Student Outcomes. AB - Self-report surveys are widely used to measure adolescent risk behavior and academic adjustment, with results having an impact on national policy, assessment of school quality, and evaluation of school interventions. However, data obtained from self-reports can be distorted when adolescents intentionally provide inaccurate or careless responses. The current study illustrates the problem of invalid respondents in a sample (N = 52,012) from 323 high schools that responded to a statewide assessment of school climate. Two approaches for identifying invalid respondents were applied, and contrasts between the valid and invalid responses revealed differences in means, prevalence rates of student adjustment, and associations among reports of bullying victimization and student adjustment outcomes. The results lend additional support for the need to screen for invalid responders in adolescent samples. PMID- 29795950 TI - Tree-Based Global Model Tests for Polytomous Rasch Models. AB - Psychometric measurement models are only valid if measurement invariance holds between test takers of different groups. Global model tests, such as the well established likelihood ratio (LR) test, are sensitive to violations of measurement invariance, such as differential item functioning and differential step functioning. However, these traditional approaches are only applicable when comparing previously specified reference and focal groups, such as males and females. Here, we propose a new framework for global model tests for polytomous Rasch models based on a model-based recursive partitioning algorithm. With this approach, a priori specification of reference and focal groups is no longer necessary, because they are automatically detected in a data-driven way. The statistical background of the new framework is introduced along with an instructive example. A series of simulation studies illustrates and compares its statistical properties to the well-established LR test. While both the LR test and the new framework are sensitive to differential item functioning and differential step functioning and respect a given significance level regardless of true differences in the ability distributions, the new data-driven approach is more powerful when the group structure is not known a priori-as will usually be the case in practical applications. The usage and interpretation of the new method are illustrated in an empirical application example. A software implementation is freely available in the R system for statistical computing. PMID- 29795949 TI - A Study of Reverse-Worded Matched Item Pairs Using the Generalized Partial Credit and Nominal Response Models. AB - The generalized partial credit model (GPCM) is often used for polytomous data; however, the nominal response model (NRM) allows for the investigation of how adjacent categories may discriminate differently when items are positively or negatively worded. Ten items from three different self-reported scales were used (anxiety, depression, and perceived stress), and authors wrote an additional item worded in the opposite direction to pair with each original item. Sets of the original and reverse-worded items were administered, and responses were analyzed using the two models. The NRM fit significantly better than the GPCM, and it was able to detect category responses that may not function well. Positively worded items tended to be more discriminating than negatively worded items. For the depression scale, category boundary locations tended to have a larger range for the positively worded items than for the negatively worded items from both models. Some pairs of items functioned comparably when reverse-worded, but others did not. If an examinee responds in an extreme category to an item, the same examinee is not necessarily likely to respond in an extreme category at the opposite end of the rating scale to a similar item worded in the opposite direction. Results of this study may support the use of scales composed of items worded in the same direction, and particularly in the positive direction. PMID- 29795951 TI - Examining Construct Congruence for Psychometric Tests: A Note on an Extension to Binary Items and Nesting Effects. AB - This article extends the procedure outlined in the article by Raykov, Marcoulides, and Tong for testing congruence of latent constructs to the setting of binary items and clustering effects. In this widely used setting in contemporary educational and psychological research, the method can be used to examine if two or more homogeneous multicomponent instruments with distinct components measure the same construct. The approach is useful in scale construction and development research as well as in construct validation investigations. The discussed method is illustrated with data from a scholastic aptitude assessment study. PMID- 29795952 TI - Evaluation of Two Methods for Modeling Measurement Errors When Testing Interaction Effects With Observed Composite Scores. AB - Path models with observed composites based on multiple items (e.g., mean or sum score of the items) are commonly used to test interaction effects. Under this practice, researchers generally assume that the observed composites are measured without errors. In this study, we reviewed and evaluated two alternative methods within the structural equation modeling (SEM) framework, namely, the reliability adjusted product indicator (RAPI) method and the latent moderated structural equations (LMS) method, which can both flexibly take into account measurement errors. Results showed that both these methods generally produced unbiased estimates of the interaction effects. On the other hand, the path model-without considering measurement errors-led to substantial bias and a low confidence interval coverage rate of nonzero interaction effects. Other findings and implications for future studies are discussed. PMID- 29795954 TI - A Comparison of Methods for Estimating Relationships in the Change Between Two Time Points for Latent Variables. AB - Collection and analysis of longitudinal data is an important tool in understanding growth and development over time in a whole range of human endeavors. Ideally, researchers working in the longitudinal framework are able to collect data at more than two points in time, as this will provide them with the potential for a deeper understanding of the development processes under study and a much broader array of statistical modeling options. However, in some circumstances data collection is limited to only two time points, perhaps because of resource limitations, issues with the context in which the data are collected, or the nature of the trait under study. In such instances, researchers may still want to learn about complex relationships in the data, such as the correlation between changes in latent traits that are being measured. However, with only two data points, standard approaches for modeling such relationships, such as growth curve modeling, cannot be used. The current simulation study compares the performance of two methods for estimating the correlations among changes in latent variables between two points in time, the two-wave latent change score model and the latent difference factor model. Results of the simulation study showed that both methods yielded generally accurate estimates of the correlation between changes in a latent trait, with relatively small standard errors. Estimation bias and standard errors were lower with larger samples, larger factor loading magnitudes, and more indicators per factor. Further comparisons between the methods and implications of these results are discussed. PMID- 29795953 TI - Curve of Factors Model: A Latent Growth Modeling Approach for Educational Research. AB - A first-order latent growth model assesses change in an unobserved construct from a single score and is commonly used across different domains of educational research. However, examining change using a set of multiple response scores (e.g., scale items) affords researchers several methodological benefits not possible when using a single score. A curve of factors (CUFFS) model assesses change in a construct from multiple response scores but its use in the social sciences has been limited. In this article, we advocate the CUFFS for analyzing a construct's latent trajectory over time, with an emphasis on applying this model to educational research. First, we present a review of longitudinal factorial invariance, a condition necessary for ensuring that the measured construct is the same across time points. Next, we introduce the CUFFS model, followed by an illustration of testing factorial invariance and specifying a univariate and a bivariate CUFFS model to longitudinal data. To facilitate implementation, we include syntax for specifying these statistical methods using the free statistical software R. PMID- 29795955 TI - A Multilevel Bifactor Approach to Construct Validation of Mixed-Format Scales. AB - Wording effects associated with positively and negatively worded items have been found in many scales. Such effects may threaten construct validity and introduce systematic bias in the interpretation of results. A variety of models have been applied to address wording effects, such as the correlated uniqueness model and the correlated traits and correlated methods model. This study presents the multilevel bifactor approach to handling wording effects of mixed-format scales used in a multilevel context. The Students Confident in Mathematics scale is used to illustrate this approach. Results from comparing a series of models showed that positive and negative wording effects were present at both the within and the between levels. When the wording effects were ignored, the within-level predictive validity of the Students Confident in Mathematics scale was close to that under the multilevel bifactor model. However, at the between level, a lower validity coefficient was observed when ignoring the wording effects. Implications for applied researchers are discussed. PMID- 29795956 TI - The Impact of Model Parameterization and Estimation Methods on Tests of Measurement Invariance With Ordered Polytomous Data. AB - Evaluations of measurement invariance provide essential construct validity evidence-a prerequisite for seeking meaning in psychological and educational research and ensuring fair testing procedures in high-stakes settings. However, the quality of such evidence is partly dependent on the validity of the resulting statistical conclusions. Type I or Type II errors can render measurement invariance conclusions meaningless. The present study used Monte Carlo simulation methods to compare the effects of multiple model parameterizations (linear factor model, Tobit factor model, and categorical factor model) and estimators (maximum likelihood [ML], robust maximum likelihood [MLR], and weighted least squares mean and variance-adjusted [WLSMV]) on the performance of the chi-square test for the exact-fit hypothesis and chi-square and likelihood ratio difference tests for the equal-fit hypothesis for evaluating measurement invariance with ordered polytomous data. The test statistics were examined under multiple generation conditions that varied according to the degree of metric noninvariance, the size of the sample, the magnitude of the factor loadings, and the distribution of the observed item responses. The categorical factor model with WLSMV estimation performed best for evaluating overall model fit, and the categorical factor model with ML and MLR estimation performed best for evaluating change in fit. Results from this study should be used to inform the modeling decisions of applied researchers. However, no single analysis combination can be recommended for all situations. Therefore, it is essential that researchers consider the context and purpose of their study. PMID- 29795957 TI - Using Cluster Bootstrapping to Analyze Nested Data With a Few Clusters. AB - Cluster randomized trials involving participants nested within intact treatment and control groups are commonly performed in various educational, psychological, and biomedical studies. However, recruiting and retaining intact groups present various practical, financial, and logistical challenges to evaluators and often, cluster randomized trials are performed with a low number of clusters (~20 groups). Although multilevel models are often used to analyze nested data, researchers may be concerned of potentially biased results due to having only a few groups under study. Cluster bootstrapping has been suggested as an alternative procedure when analyzing clustered data though it has seen very little use in educational and psychological studies. Using a Monte Carlo simulation that varied the number of clusters, average cluster size, and intraclass correlations, we compared standard errors using cluster bootstrapping with those derived using ordinary least squares regression and multilevel models. Results indicate that cluster bootstrapping, though more computationally demanding, can be used as an alternative procedure for the analysis of clustered data when treatment effects at the group level are of primary interest. Supplementary material showing how to perform cluster bootstrapped regressions using R is also provided. PMID- 29795958 TI - Exploring Incomplete Rating Designs With Mokken Scale Analysis. AB - Recent research has explored the use of models adapted from Mokken scale analysis as a nonparametric approach to evaluating rating quality in educational performance assessments. A potential limiting factor to the widespread use of these techniques is the requirement for complete data, as practical constraints in operational assessment systems often limit the use of complete rating designs. In order to address this challenge, this study explores the use of missing data imputation techniques and their impact on Mokken-based rating quality indicators related to rater monotonicity, rater scalability, and invariant rater ordering. Simulated data and real data from a rater-mediated writing assessment were modified to reflect varying levels of missingness, and four imputation techniques were used to impute missing ratings. Overall, the results indicated that simple imputation techniques based on rater and student means result in generally accurate recovery of rater monotonicity indices and rater scalability coefficients. However, discrepancies between violations of invariant rater ordering in the original and imputed data are somewhat unpredictable across imputation methods. Implications for research and practice are discussed. PMID- 29795959 TI - Examining Measurement Invariance and Differential Item Functioning With Discrete Latent Construct Indicators: A Note on a Multiple Testing Procedure. AB - A latent variable modeling method for studying measurement invariance when evaluating latent constructs with multiple binary or binary scored items with no guessing is outlined. The approach extends the continuous indicator procedure described by Raykov and colleagues, utilizes similarly the false discovery rate approach to multiple testing, and permits one to locate violations of measurement invariance in loading or threshold parameters. The discussed method does not require selection of a reference observed variable and is directly applicable for studying differential item functioning with one- or two-parameter item response models. The extended procedure is illustrated on an empirical data set. PMID- 29795960 TI - Molecular phylogeny and a new Iranian species of Caudospora (Sydowiellaceae, Diaporthales). AB - For the first time, molecular phylogenetic data on the peculiar diaporthalean genus Caudospora are available. Macro- and microscopic morphology and phylogenetic multilocus analyses of partial nuc SSU-ITS-LSU rDNA, cal, ms204, rpb1, rpb2, tef1 and tub2 sequences revealed two distinct species of Caudospora, which are described and illustrated by light and scanning electron microscopy. Caudospora iranica is described as a new species from corticated dead twigs of Quercus sp. collected in Iran. It differs from the generic type, C. taleola, mainly by coarsely verrucose ascospores. The asexual morph of C. taleola on natural substrate is described and illustrated. Caudospora taleola is neotypified, and it is recorded from Iran for the first time. Phylogenetic analyses of a multigene matrix containing a representative selection of Diaporthales from four loci (ITS, LSU rDNA, rpb2 and tef1) revealed a placement of Caudospora within Sydowiellaceae. PMID- 29795961 TI - An efficient system to fund science: from proposal review to peer-to-peer distributions. AB - This paper presents a novel model of science funding that exploits the wisdom of the scientific crowd. Each researcher receives an equal, unconditional part of all available science funding on a yearly basis, but is required to individually donate to other scientists a given fraction of all they receive. Science funding thus moves from one scientist to the next in such a way that scientists who receive many donations must also redistribute the most. As the funding circulates through the scientific community it is mathematically expected to converge on a funding distribution favored by the entire scientific community. This is achieved without any proposal submissions or reviews. The model furthermore funds scientists instead of projects, reducing much of the overhead and bias of the present grant peer review system. Model validation using large-scale citation data and funding records over the past 20 years show that the proposed model could yield funding distributions that are similar to those of the NSF and NIH, and the model could potentially be more fair and more equitable. We discuss possible extensions of this approach as well as science policy implications. PMID- 29795962 TI - Calibration to improve forward model simulation of microwave emissivity at GPM frequencies over the U.S. Southern Great Plains. AB - Better estimation of land surface microwave emissivity promises to improve over land precipitation retrievals in the GPM era. Forward models of land microwave emissivity are available but have suffered from poor parameter specification and limited testing. Here, forward models are calibrated and the accompanying change in predictive power is evaluated. With inputs (e.g., soil moisture) from the Noah land surface model and applying MODIS LAI data, two microwave emissivity models are tested, the Community Radiative Transfer Model (CRTM) and Community Microwave Emission Model (CMEM). The calibration is conducted with the NASA Land Information System (LIS) parameter estimation subsystem using AMSR-E based emissivity retrievals for the calibration dataset. The extent of agreement between the modeled and retrieved estimates is evaluated using the AMSR-E retrievals for a separate 7-year validation period. Results indicate that calibration can significantly improve the agreement, simulating emissivity with an across-channel average root-mean-square-difference (RMSD) of about 0.013, or about 20% lower than if relying on daily estimates based on climatology. The results also indicate that calibration of the microwave emissivity model alone, as was done in prior studies, results in as much as 12% higher across-channel average RMSD, as compared to joint calibration of the land surface and microwave emissivity models. It remains as future work to assess the extent to which the improvements in emissivity estimation translate into improvements in precipitation retrieval accuracy. PMID- 29795963 TI - Sensory characteristics of liquids thickened with commercial thickeners to levels specified in the International Dysphagia Diet Standardization Initiative (IDDSI) framework. AB - Sensory characteristics are important for the acceptance of thickened liquids, but those of liquids thickened to the new standards put forth by the International Dysphagia Diet Standardization Initiative (IDDSI) are unknown. This research sought to identify and rate the perception of important sensory properties of liquids thickened to levels specified in the IDDSI framework. Samples were made with water, with and without added barium sulfate, and were thickened with a cornstarch or xanthan gum based thickener. Samples were characterized using projective mapping/ultra-flash profiling to identify important sample attributes, and then with trained descriptive analysis panels to characterize those attributes in non-barium and barium thickened liquids. Three main groups of attributes were observed. Taste and flavor attributes decreased in intensity with increasing thickener. Thickener specific attributes included graininess and chalkiness for the cornstarch thickened samples, and slipperiness for the xanthan gum samples. Within the same type of thickener, ratings of thickness-related attributes (perceived viscosity, adhesiveness, manipulation, and swallowing) at different IDDSI levels were significantly different from each other. However, in non-barium samples, cornstarch samples were perceived as thicker than xanthan gum samples even though they had similar apparent viscosities at 50 s-1. On the other hand, the two thickeners had similar perceived thickness in the barium samples even though the apparent viscosities of cornstarch samples were higher than those of the xanthan gum samples. In conclusion, IDDSI levels can be distinguished based on sensory properties, but these properties may be affected by the type of thickener and medium being thickened. PMID- 29795965 TI - The Results of the Awards Are In! PMID- 29795966 TI - Keys to Building a Safe and Effective Healthcare Laser Program. PMID- 29795964 TI - Comparative Chemometric Analysis for Classification of Acids and Bases via a Colorimetric Sensor Array. AB - With the increasing availability of digital imaging devices, colorimetric sensor arrays are rapidly becoming a simple, yet effective tool for the identification and quantification of various analytes. Colorimetric arrays utilize colorimetric data from many colorimetric sensors, with the multidimensional nature of the resulting data necessitating the use of chemometric analysis. Herein, an 8 sensor colorimetric array was used to analyze select acid and basic samples (0.5 - 10 M) to determine which chemometric methods are best suited for classification quantification of analytes within clusters. PCA, HCA, and LDA were used to visualize the data set. All three methods showed well-separated clusters for each of the acid or base analytes and moderate separation between analyte concentrations, indicating that the sensor array can be used to identify and quantify samples. Furthermore, PCA could be used to determine which sensors showed the most effective analyte identification. LDA, KNN, and HQI were used for identification of analyte and concentration. HQI and KNN could be used to correctly identify the analytes in all cases, while LDA correctly identified 95 of 96 analytes correctly. Additional studies demonstrated that controlling for solvent and image effects was unnecessary for all chemometric methods utilized in this study. PMID- 29795967 TI - Helicobacter pylori Eradication Using a Light-Emitting Diode and Methylene Blue. AB - Background and aims: Eradication failures are increasing with the increasing antibiotic resistance of Helicobacter pylori.We examined the basic effect of methylene blue (MB) with sodium bicarbonate (NaHCO3) on H. pylori eradication using antimicrobial chemotherapy activated by light. Material and methods: When NaHCO3 was added to MB, the pH became basic. We smeared H. pylori on a medium with basic MB and irradiated it using a red light-emitting diode with a wavelength of 660 nm. The applied energy fluencies were 10 J/cm2 and 15 J/cm2. After 4 days of culture, the effect of this intervention was determined according to the bacterial growth area. Results: The basic effect of MB appeared between a pH of 8.6 and 9.0. The NaHCO3 concentration was between 4% and 6%. The basic effect at 15 J/cm2 was greater than that at 10 J/cm2. Conclusions: We concluded that antimicrobial chemotherapy activated by light with basic MB was effective in H. pylori eradication. PMID- 29795968 TI - Statistical analysis of complications in laser treatment under general anesthesia performed for pediatric inpatients. AB - Objective: We report relationship between complications and predictive factors of occurrence with multivariate analysis for cases of laser treatment under general anesthesia.Study Design: Pediatric patients (330 cases, aged 1 to 15 years old) who underwent laser treatment under inpatient general anesthesia against body surface hemangiomas or melanocytosis were examined for the complications. Methods: Retrospective study from medical and anesthesia records, statistical assessment was carried out using multivariate analysis by univariate and logistic regression analysis, and p value less than 0.05 was considered to be significant difference. Results: Complications were confirmed in 25%, mostly due to emergence agitation from anesthesia, and no severe complications were recognized. Multivariate analysis of factors causing complications revealed a significant difference in the limbs, the Q-switched Nd: YAG laser, and the anesthesia time of 60 minutes or longer. Conclusion: While the length of anesthesia time was reported as a factor of complication occurrence in the past, there has been no report on the extremity and the Q-switched Nd: YAG laser as significant complication factors. PMID- 29795969 TI - Clinical effects of photodynamic therapy as an adjunct to full-mouth ultrasonic scaling and root planing in treatment of chronic periodontitis. AB - Background and aims: Photodynamic therapy (PDT) is a potential strategy to eliminate infection in the specific tissue. It uses lower-power laser to activate a photosensitizing agent. Studies have shown the benefit of PDT in the periodontal treatment. The aim of this study was to evaluate the periodontal changes after applying PDT as an adjunct to one visit full-mouth SRP (scaling and root planing) with subgingival piezoelectric ultrasonic scaler compared with full mouth SRP alone. Methods: A split-mouth randomized clinical trial was designed. Twenty patients with moderate to severe chronic periodontitis were treated with subgingival piezoelectric ultrasonic device alone in control group and adjunct treated with PDT in the test group. Probing pocket depth (PD), clinical attachment level (CAL), plaque index (PI), gingival bleeding index (GBI) and gingival inflammation index (GI) were evaluated at baseline, 1 month, 3 and 6 months after treatment. Only sites with PD >= 4 mm at baseline were calculated. Results: All periodontal parameters were significantly improved in both groups at 1 month, 3 and 6 months after treatment. All parameters in test group were better than that control group, with statistically significant differences of GBI and GI (P < 0.05) at 3 and 6 months after treatment but no statistically significant differences of PD, CAL and PI. Conclusions: One visit full-mouth ultrasonic SRP seems to have good enough effort for the periodontal status till 6 months. The adjunct treatment of PDT provided positive effect in term of GBI and GI. PMID- 29795970 TI - Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy. AB - Background and Aim: Fractional CO2 lasers have been shown to provide improvement of vulvovaginal atrophy (VVA). The aim of the current study was to assess the early effect of a fractional CO2 laser system in treating postmenopausal women with clinical symptoms of VVA. Methods: 28 healthy post-menopausal women (mean age 60.1 +/- 5.55 years) with VVA-related symptoms were treated with fractional CO2 laser 3 times, in 4-week intervals. At each study visit, VHIS score and VVA symptom severity were recorded. Sexual function was assessed with the Female Sexual Function Index (FSFI). Results: One month following the first laser treatment, the mean VHIS score was significantly improved (13.89 +/- 4.25 vs. baseline 11.93 +/- 3.82; p < 0.05), and improved further at 3 and 6 months following all three laser treatments (16.43 +/- 4.20 and 17.46 +/- 4.07, respectively). Almost all VVA symptoms were significantly improved at one month following the first treatment. A further significant improvement in VVA symptoms was noted at 3 and 6 months following the third laser treatment. Following treatments, the FSFI score increased significantly (22.36 +/- 10.40 vs. baseline 13.78 +/- 7.70; p < 0.05), and remained significantly higher than baseline at the 3- and 6-month follow-up visits. Conclusion: CO2 laser therapy for post menopausal women can be considered an effective therapeutic option providing relief of symptoms already noted after one laser treatment. PMID- 29795971 TI - CO2 laser dentin surface treatment most effectively increased ceramic shear bond strength. AB - Background and aims: The purpose of this study is to determine the effect of CO2 laser irradiation in comparison with sandblasting (Sb), hydrofluoric acid (Hf) and silane coupling agent (Si) on shear bond strength (SBS) of resin cement to CAD/CAM ceramics bonded to dentin. Material and Methods: Forty-eight (CAD/CAM) ceramic discs were prepared and grouped by material, i.e. lithium disilicate (Emax CAD) and zirconia ceramic (Emax ZirCAD), distributed into four different groups: group A, lithium disilicate (Li) CO2/HF/Si; group B, Li: HF/Si; group C, zirconia (Zr) CO2/Sb/Si; group D, Zr: Sb/Si. Results: It was shown significant difference between irradiated and non-irradiated groups in terms of shear bond strength for zirconia ceramics (p value = 0.039). Conclusion: CO2 laser irradiation increases shear bond strength for both CAD/CAM ceramics bonded to dentin. PMID- 29795972 TI - Low Level Laser Therapy for Radial Nerve Palsy Patients : Our Experience. AB - Background and Aims: Peripheral nerve injury is one of the frequent complaints which is seen in the outpatient clinic of our medical institute. In previous studies we have reported on the benefits of low level laser therapy (LLLT) for central nerve system disorders, namely cerebrovascular accidents and cerebral palsy. The present study is a report on our experience of the effects of LLLT for peripheral nerve palsy. Materials and Methods: Over the past 5 years, 13 subjects visited the out-patient clinic with the chief complaint of radial nerve palsy caused by compression of the nerve through with abnormal positioning, and sleeping posture at night. The patients were treated with LLLT. A 1000 mW semi conductor laser device was used, delivering 830 nm in continuous wave at a dose of 20.1 J/cm2 /point, and five points were treated per session (i.e., 1 treatment) twice a week for 3 months (total 24 treatments). In 6 patients LLLT was combined with brace therapy. Results: Modified Daniels' manual muscle testing was used to determine the effects of LLLT for the muscle power of the extensor carpi radialis, and on completing the treatment regimen excellent improvement was observed in 9 cases out of 13. Combination treatment (laser therapy with bracing) resulted in 4 excellent cases out of 6 cases. Discussions with the patients clarified that it was important for them to learn how to avoid the particular posture that could cause them radial nerve palsy in daily life in order to have continuous benefits from the treatment. Conclusion: The present study demonstrated that LLLT was an effective form of treatment for radial nerve palsy. In addition, patients were advised to avoid any incorrect posture which might induce radial nerve palsy. PMID- 29795974 TI - Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone. AB - Context: The assessment absolute bioavailability of oral hydrocortisone is complicated by its saturable binding to cortisol binding globulin (CBG). Previous assessment of bioavailability used a cortisol radioimmunoassay which has cross reactivity with other steroids. Salivary cortisone is a measure of free cortisol and LC-MS/MS is the gold standard method for measuring steroids. We here report the absolute bioavailability of hydrocortisone calculated using serum cortisol and salivary cortisone measured by LC-MS/MS. Methods: 14 healthy male dexamethasone suppressed volunteers were administered 20 mg hydrocortisone either intravenously or orally by tablet. Samples of serum and saliva were taken and measured for cortisol and cortisone by LC-MS/MS. Serum cortisol was corrected for saturable binding using published data and pharmacokinetic parameters derived using the program WinNonlin. Results: The mean (95% CI) bioavailability of oral hydrocortisone calculated from serum cortisol, unbound serum cortisol and salivary cortisone was 1.00 (0.89-1.14); 0.88 (0.75-1.05); and 0.93 (0.83-1.05), respectively. Conclusion: The data confirm that, after oral administration, hydrocortisone is completely absorbed. The data derived from serum cortisol corrected for protein binding, and that from salivary cortisone, are similar supporting the concept that salivary cortisone reflects serum free cortisol levels and that salivary cortisone can be used as a non-invasive method for measuring the pharmacokinetics of hydrocortisone. PMID- 29795973 TI - Dye laser treatment for hemorrhagic vascular lesions. AB - Background and aims: It is generally thought that bleeding from a hemangioma is difficult to stop. With development of the long pulse dye laser (LPDL), it has become possible to treat hemangioma with a large blood vessel diameter. Thus, it is effective in treating infantile hemangioma and pyogenic granuloma. Materials and methods: Five patients who visited our hospital from July 2015 to July 2017 due to hemorrhagic hemangioma were treated using a flash lamp excitation pulse dye laser with parameters of 7 mm spot size, 3 msec pulse width, fluence 12 14J/cm2, DCD 30 msec, and delay 30 msec. Results: The bleeding not only stopped, but the raised lesion was flattened in all cases. Conclusions: LPDL is effective for both infantile hemangioma and pyogenic granuloma. It not only stops bleeding, but also treats the vascular lesions. PMID- 29795975 TI - Balance in Positive Emotional Expressivity Across School Contexts Relates to Kindergarteners' Adjustment. AB - : Positive emotional expressivity has been associated with increased social competence and decreased maladjustment in childhood. However, a few researchers have found null or even positive associations between positive emotional expressivity and maladjustment, which suggests that there may be nuanced associations of positive expressivity, perhaps as a function of the social context in which it is expressed. We examined whether observed positive emotional expressivity balance across peer-oriented/recreational and learning contexts predicted kindergarten children's adjustment (N = 301). Research findings: Higher positive expressivity during lunch/recess compared to positive expressivity in the classroom was associated with lower teacher-student conflict, externalizing behaviors, and depressive symptoms. In addition, overall positive emotional expressivity predicted lower externalizing behaviors as well as lower depressive and anxiety symptoms. Practice or policy: The results suggest the importance of assessing observed positive emotional expressivity in context as a potential indicator of children's maladjustment risk and the need for children to adapt their emotions to different contexts. Implications for assessing and supporting positive emotional expression balance and training emotional regulation in school are discussed. PMID- 29795976 TI - Impaired Cerebral Perfusion in Multiple Sclerosis: Relevance of Endothelial Factors. AB - Magnetic resonance imaging techniques measuring in vivo brain perfusion and integrity of the blood-brain barrier have developed rapidly in the past decade, resulting in a wide range of available methods. This review first discusses their principles, possible pitfalls, and potential for quantification and outlines clinical application in neurological disorders. Then, we focus on the endothelial cells of the blood-brain barrier, pointing out their contribution in regulating vascular tone by production of vasoactive substances. Finally, the role of these substances in brain hypoperfusion in multiple sclerosis is discussed. PMID- 29795977 TI - Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. AB - Aim: The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD). Materials and methods: We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta analysis of efficacy and safety data from DBRPCTs was performed. Results: Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4 6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, p<0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, p<0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, p<0.001; WMD =-2.07, 95% CI =-1.08, -3.05, p<0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (>=50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, p=0.024, number needed-to-treat [NNT] =7, 95% CI =3, 333, p=0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, p<0.001, NNT =4, 95% CI =3, 6, p<0.001). Less consistent results emerged from patient-rated global impression-based response (p=0.15) and clinical global impression for deutetrabenazine (p=0.088), and for clinical global impression change for valbenazine (p=0.67). In an open-label extension (OLE) study of deutetrabenazine (<=54 weeks) and a dose-blinded valbenazine study (<=48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed. Conclusion: The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high quality, meta-analyzable data are available for tetrabenazine in patients with TD. PMID- 29795980 TI - Mathematical Model for Small Size Time Series Data of Bacterial Secondary Metabolic Pathways. AB - Measuring the concentrations of metabolites and estimating the reaction rates of each reaction step consisting of metabolic pathways are significant for an improvement in microorganisms used in maximizing the production of materials. Although the reaction pathway must be identified for such an improvement, doing so is not easy. Numerous reaction steps have been reported; however, the actual reaction steps activated vary or change according to the conditions. Furthermore, to build mathematical models for a dynamical analysis, the reaction mechanisms and parameter values must be known; however, to date, sufficient information has yet to be published for many cases. In addition, experimental observations are expensive. A new mathematical approach that is applicable to small sample data, and that requires no detailed reaction information, is strongly needed. S-system is one such model that can use smaller samples than other ordinary differential equation models. We propose a simplified S-system to apply minimal quantities of samples for a dynamic analysis of the metabolic pathways. We applied the model to the phenyl lactate production pathway of Escherichia coli. The model obtained suggests that actually activated reaction steps and feedback are inhibitions within the pathway. PMID- 29795979 TI - Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-kappaB signaling pathways in diabetic nephropathy. AB - Introduction: Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. Materials and methods: Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). Results: RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) signaling pathways. Conclusion: RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-kappaB pathways. PMID- 29795978 TI - Computer-aided design of amino acid-based therapeutics: a review. AB - During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics. Amino acid based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency. Computational techniques play a key role to design and develop the amino acid based therapeutics such as proteins, peptides and peptidomimetics. In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics. Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics. Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target "undruggable" intracellular protein-protein interactions. Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted. The most advanced computational techniques developed to design novel peptidomimetics are also summarized. PMID- 29795981 TI - Disrupted interhemispheric functional connectivity in chronic insomnia disorder: a resting-state fMRI study. AB - Background: Abnormalities in both cerebral structure and intrinsic activity have been increasingly reported in patients with chronic insomnia disorder (CID). However, the inter-hemispheric integration function in CID is still not well understood. Functional homotopy reflects an essential aspect of the intrinsic functional architecture involved in interhemispheric coordination. Methods: In this study, voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with CID (n=29). Results: Reduced homotopic connectivity was observed in the middle occipital/posterior middle temporal gyrus in CID patients relative to control subjects. Further analyses demonstrated different insomnia-related heterotopic connectivity patterns in the right and left middle occipital/posterior middle temporal gyrus. Furthermore, within the CID group, the connectivity coefficient within the connectivity network of the middle occipital/posterior middle temporal gyrus was associated with anxiety measures. Conclusion: Negative significant findings of group differences were found in terms of both the local gray matter density and fractional anisotropy of the white matter skeletal measures in this study; this structural finding, together with the results of VMHC, suggested that disruptions in the intrinsic functional architecture of interhemispheric communication associated with CID can be observed in the absence of detectable microstructural or local morphometric changes in white and gray matter. PMID- 29795983 TI - Emerging Topics and Innovative Methodologies in Cannabis Research. AB - Cannabis use is ascendant in our society, affecting the health of our citizens, our social norms and social structures, and our economies. This special issue brings together a diverse set of research manuscripts that push the borders of our understanding of burgeoning cannabis use and displays innovative methods developed to study these phenomena. PMID- 29795982 TI - Synchronization within, and interactions between, the default mode and dorsal attention networks in relapsing-remitting multiple sclerosis. AB - Background and purpose: The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients. Patients and methods: Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers. Results: Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score (rho = 0.379, p = 0.036). Conclusion: Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients. PMID- 29795984 TI - Reexamining IFN-gamma Stimulation of De Novo NAD+ in Monocyte-Derived Macrophages. PMID- 29795985 TI - Decreased survival in patients with carcinoma of axillary tail versus upper outer quadrant breast cancers: a SEER population-based study. AB - Background: Carcinoma of the axillary tail of Spence (CATS) is a poorly studied type of breast cancer. The clinicopathological characteristics and prognostic features of CATS are unclear. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified 149,026 patients diagnosed with upper outer quadrant breast cancer (UOBC) (n=146,343) or CATS (n=2,683). The median follow-up was 88 months. The primary and secondary outcomes were breast cancer-specific survival (BCSS) and overall survival. The survival outcomes of UOBC and CATS were compared using competing risks analysis, log-rank test, Cox proportional hazards regression model, and propensity score matching method. Multivariate logistic regression was utilized to present the relationship between CATS and lymph node (LN) metastasis. Results: CATS presented a higher grade, higher negative hormone receptor rate, and more positive nodal metastasis. The 10-year BCSS rate was worse for CATS than for UOBC (85.1% vs 87.3%, P=0.001). The multivariate Cox analysis showed a higher hazard ratio (HR) for CATS over UOBC (BCSS: HR =1.20, P=0.001; overall survival: HR =1.11, P=0.019). The difference in the BCSS was also observed in a 1:1 matched cohort (BCSS P=0.019). A subgroup analysis revealed the inferior outcomes of CATS in the metastatic LN subgroup and the hormone receptor-negative subgroup. The multivariate logistic regression indicated that CATS is an independent contributing factor to LN metastasis. Conclusion: CATS had distinct clinicopathological characteristics and was more likely associated with LN metastasis. Compared to UOBC, CATS had adverse impacts on BCSS. PMID- 29795987 TI - The lncRNA myocardial infarction associated transcript-centric competing endogenous RNA network in non-small-cell lung cancer. AB - Background: The leading cause of death for cancer is lung cancer, of which the majority subtype is non-small cell lung cancer (NSCLC). Recent studies have shown long non-coding RNAs are transcribed and contribute to cancer. Previous study has shown that a few single nucleotide polymorphisms (SNPs) in myocardial infarction associated transcript (MIAT) were associated with some diseases or function as competing endogenous RNA (ceRNA) in some cancer. Patients and methods: We performed bioinformatic methods for analyzing RNA-seq and miRNA-seq data of NSCLC from The Cancer Genome Atlas database. 1352 NSCLC patients and 1320 cancer-free controls for genotyping, and dual luciferase reporter assay, real-time PCR are performed in A549 and H1975 lung cancer cell lines. Results are analyzed by SPSS v16.0. Results: In the present study, we focus on the role of over-expression MIAT in NSCLC. We confirmed that rs1061451 T>C (allele odds ratio = 0.22; P < 0.01) was associated with NSCLC. Furthermore, we constructed MIAT-centric ceRNA network, and three mRNAs (MYO1B, SGK1 and WNT9A) was identified as targets by MIAT via miR-133a-5p. Conclusion: C-containing genotypes of MIAT rs1061451 were protective factor of NSCLC, and MIAT, which may act as ceRNA via miR-133a-5p, modulated MYO1B, SGK1 and WNT9A expression level. PMID- 29795986 TI - MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: a pooled analysis from the M-SKIP project. AB - Purpose: Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ultimately survival. The aim of this study was to evaluate whether MC1R variants predicted melanoma risk independently of at-risk phenotypic characteristics. Materials and methods: Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies. All the studies had information on MC1R gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype. Results: The presence of any MC1R variant was associated with melanoma risk independently of phenotypic characteristics (OR 1.60; 95% CI 1.36-1.88). Inclusion of MC1R variants in a risk prediction model increased melanoma predictive accuracy (area under the receiver-operating characteristic curve) by 0.7% over a base clinical model (P=0.002), and 24% of participants were better assessed (net reclassification index 95% CI 20%-30%). Subgroup analysis suggested a possibly stronger role of MC1R in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%). Conclusion: The authors suggest that measuring the MC1R genotype might result in a benefit for melanoma prediction. The results could be a valid starting point to guide the development of scientific protocols assessing melanoma risk prediction tools incorporating the MC1R genotype. PMID- 29795988 TI - Overexpression of chloride channel-3 predicts unfavorable prognosis and promotes cellular invasion in gastric cancer. AB - Background: Chloride channel-3 (CLC-3) has been reported to promote the proliferation and invasion in various tumors, yet little is known about its role in gastric cancer. In the present study, we investigated the clinical significance of CLC-3 and its biological role in gastric cancer. Methods: Bioinformatic analysis, immunohistochemical staining, quantitative real-time polymerase chain reaction and Western blot assay were used to assess the expression of CLC-3 and its clinical significance in gastric cancer. The biological role of CLC-3 and its underlying mechanism were detected through in vitro experiments. Results: CLC-3 was highly expressed in gastric cancer tissues and cell lines, and high levels of CLC-3 were significantly associated with adverse clinicopathological parameters and shorter overall survival time in patients with gastric cancer. Functional studies revealed that silencing of CLC-3 decreased, while overexpression promoted, the proliferation, migration and invasion of gastric cancer cells in vitro. Mechanistic studies suggested that canonical TGF-beta/Smad signaling pathway is involved in CLC-3-induced gastric cancer cells proliferation, migration and invasion. Conclusion: These findings indicate the vital role of CLC-3 in gastric cancer progression and its potential role of a therapeutic target for treatment. PMID- 29795989 TI - Preoperative serum apolipoprotein A-I levels predict long-term survival in non muscle-invasive bladder cancer patients. AB - Introduction: The aim of this study was to elucidate the association between apolipoprotein A-I (Apo A-I) and overall survival (OS) as well as cancer-specific survival (CSS) in non-muscle-invasive bladder cancer (NMIBC) patients undergoing transurethral resection of bladder tumor (TURBT). Patients and methods: We retrospectively collected data of 470 eligible patients diagnosed with NMIBC and who received TURBT between January 2004 and December 2011. Pretreatment blood indexes were examined. The association of Apo A-I with clinicopathological characteristics was further analyzed by dichotomizing our sample into those with Apo A-I <= 1.19 g/L (low Apo A-I group) and those with Apo A-I > 1.19 g/L (high Apo A-I group). OS and CSS were estimated by Kaplan-Meier analysis and the log rank test was used to compare differences between groups. Univariate and multivariate Cox regression analyses were plotted to assess the prognostic value of Apo A-I in NMIBC patients. In addition, subgroup analyses were performed according to the risk classification of the International Bladder Cancer Group. Results: In the overall population, patients in the high Apo A-I group had greater 5-year OS and 5-year CSS rates as compared to those in the low Apo A-I group. Kaplan-Meier survival analysis revealed that higher albumin, Apo A-I, and hemoglobin levels were associated with greater OS and CSS while elevated neutrophil-lymphocyte ratio was associated with worse OS and CSS in the overall and high-risk population rather than low- and intermediate-risk population. Furthermore, Apo A-I was shown to be an independent predictor in the overall population (for OS, hazard ratio [HR], 0.364, 95% confidence interval [CI], 0.221 0.598, p < 0.001; for CSS, HR, 0.328, 95% CI, 0.185-0.583, p < 0.001) and high risk patients (for OS, HR, 0.232, 95% CI 0.121-0.443, p < 0.001; for CSS, HR, 0.269, 95% CI, 0.133-0.541, p < 0.001). Conclusion: These results suggest that Apo A-I level could potentially serve as a useful prognostic indicator for therapeutic decision making in NMIBC patients. PMID- 29795990 TI - Prognostic factors for survival among patients with primary bone sarcomas of small bones. AB - Background: Primary bone sarcomas of the hands or feet are rare lesions and poorly documented. Moreover, the prognostic determinants of bone sarcomas of the hands or feet have not been reported. Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) program database was used to screen patients with bone sarcomas of the hands or feet from 1973 to 2013, with attention paid to chondrosarcoma, Ewing sarcoma, and osteosarcoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan-Meier method was used to obtain OS and CSS curves. Results: A total of 457 cases were selected from the SEER database. Chondrosarcoma was the most common form of lesion in hands or feet or both, followed by Ewing sarcoma and osteosarcoma. The 5- and 10-year OS rates of the entire group were 75.7% and 66.1%, respectively. The 5- and 10-year CSS rates were 78.7% and 73.7%, respectively. Multivariate analysis revealed that age under 40 years, localized stage, low grade, surgical treatment, and first primary tumor were associated with improved OS, and decade of diagnosis, stage, grade, and surgery were independent predictors of CSS. However, no significant differences were observed in OS and CSS among patients with different primary tumor locations and tumor subtypes. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis. Conclusion: Among patients with primary bone sarcomas of the hands or feet, younger age (<40 years), localized stage, low grade, surgical treatment, and first primary tumor are favorable factors for prolonging survival. PMID- 29795991 TI - Gastrointestinal Lesions in African American Patients With Iron Deficiency Anemia. AB - Background: Iron deficiency anemia (IDA) is a frequent disorder that is associated with many serious diseases. However, the findings of an evaluation of IDA-associated gastrointestinal disorders are lacking among African American patients. Aim: To determine the most prevalent gastrointestinal lesions among African American patients with IDA especially in young men. Methods: We reviewed medical records (n = 422) of patients referred for evaluation of IDA from 2008 to 2012. Iron deficiency anemia was diagnosed using clinical laboratory tests. The results of esophagogastroduodenoscopy, colonoscopy, and pathology specimens along with demographic data were abstracted and analyzed using Stata. Results: The mean age was 61.9 years, and 50.5% were women. In total, 189 patients (45%) had gross gastrointestinal (GI) bleeding. The most frequent diagnoses were gastritis (40%), benign colonic lesions (13%), esophagitis (9%), gastric ulcer (6%), and duodenitis (6%). GI bleeding was significantly more frequent in men (P = 0.001). Benign and malignant colonic lesions were significantly more present among older patients: 16% vs 6% (P = .005) and 5% vs 0% (P = .008), respectively. Colitis was more prevalent in younger patients (?50): 11% vs 2% (P = .001). In patients with gross lower GI bleeding, the top diagnoses were gastritis (25%), benign colon tumors (10%), and duodenitis (6%). Colon cancer was diagnosed among 15 patients, and all these patients were older than 50 years of age. Conclusions: Gastritis and colonic lesions are most common associated lesions with IDA among African Americans. So bidirectional endoscopy is required for unrevealing of the cause of IDA in asymptomatic patients. PMID- 29795992 TI - Genetically Engineered Strains: Application and Advances for 1,3-Propanediol Production from Glycerol. AB - 1,3-Propanediol (1,3-PD) is one of the most important chemicals widely used as monomers for synthesis of some commercially valuable products, including cosmetics, foods, lubricants and medicines. Although 1,3-PD can be synthesized both chemically and biosynthetically, the latter offers more merits over chemical approach as it is economically viable, environmentally friendly and easy to carry out. The biosynthesis of 1,3-PD can be done by transforming glycerol or other similar substrates using some bacteria, such as Clostridium butyricum and Klebsiella pneumoniae. However, these natural microorganisms pose some bottlenecks like low productivity and metabolite inhibition. To overcome these problems, recent research efforts have been focused more on the development of new strains by modifying the genome through different techniques, such as mutagenesis and genetic engineering. Genetically engineered strains obtained by various strategies cannot only gain higher yield than wild types, but also overcome some of the barriers in production by the latter. This review paper presents an overview on the recent advances in the technological approaches to develop genetically engineered microorganisms for efficient biosynthesis of 1,3 PD. PMID- 29795994 TI - Solid-State Fermentation of Carrot Pomace for the Production of Inulinase by Penicillium oxalicum BGPUP-4. AB - Inulinases are an important class of industrial enzymes which are used for the production of high-fructose syrup and fructooligosaccharides. Inulin, a polyfructan, is generally employed for the production of inulinase, which is a very expensive substrate. A number of agroindustrial residues have been used for cost-effective production of inulinases. In the present study, carrot pomace was selected as a substrate for the production of inulinase by Penicillium oxalicum BGPUP-4 in solid-state fermentation. Carrot pomace is one of the good substrates for bioprocesses, because it is rich in soluble and insoluble carbohydrates. A central composite rotatable design (CCRD) used in response surface methodology was employed for the optimal production of inulinase from carrot pomace. Using CCRD, 15 runs were practiced to optimize the range of three independent variables: moisture content (70-90%), incubation time (4-6 days) and pH (5.0-7.0) for inulinase production. Carrot pomace supplemented with 0.5% inulin as an inducer, 0.2% NH4H2PO4, 0.2% NaNO3, 0.2% KH2PO4, 0.05% MgSO4.7H2O and 0.001% FeSO4.7H2O was used for the production of inulinase in solid-state fermentation at 30 degrees C. Inulinase production (322.10 IU per g of dry substrate) was obtained under the optimized conditions, i.e. moisture content of 90%, incubation time 4 days and pH=7.0. The corresponding inulinase/invertase (I/S) ratio (3.38) was also high, which indicates the inulolytic nature of the enzyme. Multiple correlation coefficients R for inulinase production and I/S ratio were 0.9995 and 0.9947, respectively. The R value very close to one indicates an excellent correlation between experimental and predicted results. PMID- 29795995 TI - Dye-Affinity Nanofibrous Membrane for Adsorption of Lysozyme: Preparation and Performance Evaluation. AB - Polyacrylonitrile (PAN) nanofibrous membrane was prepared by an electrospinning technique. After heat treatment and alkaline hydrolysis, the weak ion exchange membrane was grafted with chitosan molecule and then covalently immobilized with a Cibacron Blue F3GA (CB). Fibre diameter, porosity and pore size of the membrane and immobilized dye density were characterized. Furthermore, the membrane was applied to evaluate the binding performance of lysozyme under various operating parameters (pH, chitosan mass per volume ratio, dye concentration, ionic strength and temperature) in batch mode. The experimental results were directly applied to purify lysozyme from chicken egg white by membrane chromatography. The results showed that the capture efficiency, recovery yield and purification factor were 90 and 87%, and 47-fold, respectively, in a single step. The binding capacity remained consistent after five repeated cycles of adsorption-desorption operations. This work demonstrates that the dye-affinity nanofibrous membrane holds great potential for purification of lysozyme from real feedstock. PMID- 29795996 TI - Acrylamide Mitigation in Fried Kochchi Kesel Chips Using Free and Immobilized Fungal Asparaginase. AB - Acrylamide is formed when food products are fried at high temperature. Food researchers are constantly working on developing efficient methods for mitigating acrylamide in fried foods. In the present study, asparaginase from Aspergillus terreus was used for the pretreatment of kochchi kesel banana slices before frying to mitigate acrylamide formation during frying. The soaking and frying conditions were optimized using free and chitosan-immobilized asparaginase. The optimal soaking temperature and time were found to be 60 degrees C and 20 min, respectively. The optimal activity of free and chitosan-immobilized asparaginase was found to be 5 U/mL. The optimal frying temperature and time for both free and chitosan-immobilized asparaginase were found to be 180 degrees C for 25 min with an acrylamide mass fraction of 1866 and 954 ug/kg, respectively. The kinetics and thermodynamics of enzymatic mitigation of acrylamide in kochchi kesel chips were also studied. It was concluded that the chitosan-immobilized asparaginase pretreatment of kochchi kesel slices is an effective method for mitigation of acrylamide. PMID- 29795993 TI - Applications of Microbial Enzymes in Food Industry. AB - The use of enzymes or microorganisms in food preparations is an age-old process. With the advancement of technology, novel enzymes with wide range of applications and specificity have been developed and new application areas are still being explored. Microorganisms such as bacteria, yeast and fungi and their enzymes are widely used in several food preparations for improving the taste and texture and they offer huge economic benefits to industries. Microbial enzymes are the preferred source to plants or animals due to several advantages such as easy, cost-effective and consistent production. The present review discusses the recent advancement in enzyme technology for food industries. A comprehensive list of enzymes used in food processing, the microbial source of these enzymes and the wide range of their application are discussed. PMID- 29795997 TI - Property Improvement of alpha-Amylase from?Bacillus stearothermophilus by Deletion of Amino Acid?Residues Arginine 179 and Glycine 180. AB - To improve the properties of alpha-amylase from Bacillus stearothermophilus (AmyS), a deletion mutant AmyS?R179-G180 was constructed by deleting arginine (Arg179) and glycine (Gly180) using site-directed mutagenesis. AmyS and AmyS?R179 G180 were expressed in Bacillus subtilis and purified by ammonium sulfate precipitation, after which the enzymatic properties were characterized and compared. By deleting amino acids Arg179 and Gly180, the thermostability of alpha amylase AmyS?R179-G180 was enhanced and the half-life at 100 degrees C significantly increased from 24 to 33 min. In addition, AmyS?R179-G180 exhibited greater acid resistance and lower calcium requirements to maintain alpha-amylase activity. The secretory capacity of the recombinant strain was evaluated by fed batch fermentation in a 7.5-litre fermentor in which high alpha-amylase activity was obtained. The highest activity reached 3300 U/mL with a high productivity of 45.8 U/(mL.h). PMID- 29795998 TI - Microencapsulation of Algal Oil Using Spray Drying Technology. AB - This work aims at developing a process of microencapsulation of algal oil containing >=40% docosahexaenoic acid (DHA) using spray drying technology. Purity Gum(r) 2000 and Capsul(r), both obtained from waxy corn starch, were chosen as the encapsulation materials. The effects of emulsification conditions on the droplet size, stability, viscosity and surface tension, and the effects of spraying conditions on the particle size, moisture content and surface oil content were investigated successively. The morphology of emulsion droplets and the microcapsules was observed by optical microscope and scanning electron microscopy. The results showed that the produced spherical microcapsules were smooth and free of pores, cracks, and surface indentation when shear velocity was 8.63 m/s in the first step of emulsification, homogenization pressure was 1.75.108 Pa and number of passes through homogenization unit was six for fine emulsification, rotational speed of spray disk was 400 s-1, and air inlet temperature was 170 degrees C. Therefore, it was concluded that the emulsification and encapsulation of algal oil containing DHA with above process was feasible. PMID- 29795999 TI - Effects of Formic or Acetic Acid on the Storage Quality? of Mixed Air-Dried Corn Stover and Cabbage Waste,?and Microbial Community Analysis. AB - A mixture of air-dried corn stover and cabbage waste was ensiled to preserve lignocellulosic biomass for use as biofuel. Furthermore, the effects of different fresh mass fractions (0.3 and 0.6%) of formic or acetic acid on the mixed silage quality were evaluated to guarantee its quality. The application of formic or acetic acid prior to mixing the silage led to higher water-soluble carbohydrate fractions than the negative control, indicating that both acids contributed to preservation of water-soluble carbohydrates during storage for 170 days. The dry matter content was also increased after storage from 90 to 170 days. It was found that the content of neutral and acid detergent fibre, cellulose and holocellulose (the sum of cellulose and hemicellulose) in mixed silage treated with formic or acetic acid was significantly lower than that obtained in the negative control. The pH and the ratio of ammoniacal nitrogen to total nitrogen in mixed silage treated with acetic acid also significantly decreased. Furthermore, the addition of formic or acetic acid significantly weakened the fermentation intensity of lactic acid, depending on the ratio of lactic to acetic acid, as well as the ratio of lactic acid to total organic acids. The number of bacterial species and their relative abundance shifted during silage mixing, wherein microbial communities at phylum level mainly consisted of Proteobacteria and Firmicutes. The dominant bacteria were also observed to shift from Lactobacillus and Enterobacter in presilage biomass to Lactobacillus and Paralactobacillus. Specifically, Enterobacter disappeared after 130 days of storage. In conclusion, the addition of a low dose of acetic acid to fresh mass (0.3%) could effectively improve the fermentation quality and is conducive to the preservation of the organic components. PMID- 29796000 TI - In-Vessel Co-Composting of Food Waste Employing Enriched Bacterial Consortium. AB - The aim of the present study is to develop a good initial composting mix using a bacterial consortium and 2% lime for effective co-composting of food waste in a 60-litre in-vessel composter. In the experiment that lasted for 42 days, the food waste was first mixed with sawdust and 2% lime (by dry mass), then one of the reactors was inoculated with an enriched bacterial consortium, while the other served as control. The results show that inoculation of the enriched natural bacterial consortium effectively overcame the oil-laden co-composting mass in the composter and increased the rate of mineralization. In addition, CO2 evolution rate of (0.81+/-0.2) g/(kg.day), seed germination index of (105+/-3) %, extractable ammonium mass fraction of 305.78 mg/kg, C/N ratio of 16.18, pH=7.6 and electrical conductivity of 3.12 mS/cm clearly indicate that the compost was well matured and met the composting standard requirements. In contrast, control treatment exhibited a delayed thermophilic phase and did not mature after 42 days, as evidenced by the maturity parameters. Therefore, a good composting mix and potential bacterial inoculum to degrade the oil are essential for food waste co-composting systems. PMID- 29796001 TI - High-Throughput rRNA Gene Sequencing Reveals High?and Complex Bacterial Diversity Associated with?Brazilian Coffee Bean Fermentation. AB - Coffee bean fermentation is a spontaneous, on-farm process involving the action of different microbial groups, including bacteria and fungi. In this study, high throughput sequencing approach was employed to study the diversity and dynamics of bacteria associated with Brazilian coffee bean fermentation. The total DNA from fermenting coffee samples was extracted at different time points, and the 16S rRNA gene with segments around the V4 variable region was sequenced by Illumina high-throughput platform. Using this approach, the presence of over eighty bacterial genera was determined, many of which have been detected for the first time during coffee bean fermentation, including Fructobacillus, Pseudonocardia, Pedobacter, Sphingomonas and Hymenobacter. The presence of Fructobacillus suggests an influence of these bacteria on fructose metabolism during coffee fermentation. Temporal analysis showed a strong dominance of lactic acid bacteria with over 97% of read sequences at the end of fermentation, mainly represented by the Leuconostoc and Lactococcus. Metabolism of lactic acid bacteria was associated with the high formation of lactic acid during fermentation, as determined by HPLC analysis. The results reported in this study confirm the underestimation of bacterial diversity associated with coffee fermentation. New microbial groups reported in this study may be explored as functional starter cultures for on-farm coffee processing. PMID- 29796002 TI - Optimization of Process Parameters for the Production of gamma-Linolenic Acid by Cunninghamella elegans CFR C07?in Submerged Fermentation. AB - The production of gamma-linolenic acid (GLA) by the fungus Cunninghamella elegans CFR C07 in submerged fermentation was studied. Culture parameters such as carbon source and incubation time were optimized. Four different extraction methods using solvents with acid washed sand, glass beads, lyophilization and Soxhlet extraction were evaluated for improved extraction of lipids from the fungal biomass after fermentation. The GLA production was initially optimized in 250-mL flask and the process was demonstrated in a 3-litre fermentor. The maximum GLA production was 882 mg/L in shake flask culture and 733 mg/L in the fermentor. The study shows that Cunninghamella elegans CFR C07 is a potent organism for the production of GLA under submerged conditions. PMID- 29796003 TI - Correlation Between Protein Primary Structure and Soluble Expression Level of HSA dAb in Escherichia coli. AB - It is widely accepted that features such as pI, length, molecular mass and amino acid (AA) sequence have a significant influence on protein solubility. Here, we mainly focused on AA composition and explored those that most affected the soluble expression level of human serum albumin (HSA) domain antibody (dAb). The soluble expression and sequence of 65 dAb variants were analysed using clustering and linear modelling. Certain AAs significantly affected the soluble expression level of dAb, with the specific AA combinations being (S, R, N, D, Q), (G, R, C, N, S) and (R, S, G); these combinations respectively affected the dAb expression level in the broth supernatant, the level in the pellet lysate and total soluble dAb. Among the 20 AAs, R displayed a negative influence on the soluble expression level, whereas G and S showed positive effects. A linear model was built to predict the soluble expression level from the sequence; this model had a prediction accuracy of 80%. In summary, increasing the content of polar AAs, especially G and S, and decreasing the content of R, was helpful to improve the soluble expression level of HSA dAb. PMID- 29796004 TI - Production of Pectinase from Bacillus sonorensis MPTD1. AB - Seven isolates from spoiled fruits and vegetables were screened for pectinase production using pectin agar plates and the most efficient bacterial strain, MPTD1, was identified as Bacillus sonorensis. Optimisation of various process parameters was done using Plackett-Burman and Box-Behnken designs and it was found that parameters like yeast extract, K2HPO4, incubation time, NaNO3 and KCl have a negative impact on pectinase production. Parameters like pH and MgSO4 and pectin mass fractions have a positive impact on pectinase production. The maximum obtained enzyme activity was 2.43 (MUM/mL)/min. This is the first report on pectinase production by Bacillus sonorensis. PMID- 29796005 TI - Molecular Characterization and Directed Evolution of a Metagenome-Derived l Cysteine Sulfinate Decarboxylase. AB - l-Cysteine sulfinate decarboxylase (CSD, EC 4.1.1.29), the rate-limiting enzyme in taurine synthesis pathway, catalyzes l-cysteine sulfinic acid to form hypotaurine. Identification of the novel CSD that could improve the biosynthetic efficiency of taurine is important. An unexplored decarboxylase gene named undec1A was identified in a previous work through sequence-based screening of uncultured soil microorganisms. Random mutagenesis through sequential error-prone polymerase chain reaction was used in Undec1A. A mutant Undec1A-1180, which was obtained from mutagenesis library, had 5.62-fold higher specific activity than Undec1A at 35 degrees C and pH=7.0. Molecular docking results indicated that amino acid residues Ala235, Val237, Asp239, Ile267, Ala268, and Lys298 in the Undec1A-1180 protein helped recognize and catalyze the substrate molecules of l cysteine sulfinic acid. These results could serve as a basis for elucidating the characteristics of the Undec1A-1180. Directed evolution technology is a convenient way to improve the biotechnological applications of metagenome-derived genes. PMID- 29796007 TI - B-chronic lymphocytic leukemia showed triple transformation, to diffuse large B cell, CD20-negative, and T-cell neoplasm during ofatumumab treatment: a case report. AB - Background: Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter's syndrome. Case presentation: We treated a 69-year-old Japanese male who was histologically diagnosed with Richter's syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/MUL and a disease status of Rai classification stage I and Binet classification B. He had high fever and hepatosplenomegaly upon Richter's transformation. The patient was treated with ofatumumab for refractory CLL, which relieved his febrile lymphadenopathy. He received a total of 11 ofatumumab courses and achieved partial remission. On the day of the 12th course of ofatumumab, his disease relapsed with febrile lymphadenopathy. Computed tomography revealed multiple liver masses and systemic lymphadenopathy, while a liver biopsy confirmed T-cell lymphoma. Concomitantly, CD20-lacking CLL cells were detected in his peripheral blood and bone marrow, and pathological examination of his left cervical lymph node biopsy showed CD20-positive DLBCL. The final diagnosis was three different types of lymphoma pathologies: (1) CD20 positive DLBCL of the lymph nodes, (2) CD20-lacking CLL of the peripheral blood and bone marrow, and (3) peripheral T-cell lymphoma (PTCL) of the liver. He received intravenous and oral dexamethasone therapy as palliative care. He died because of the rapid progression of abdominal masses 2 months after the diagnosis of triple transformation CLL. An autopsy revealed aggressive PTCL with aggressive systemic involvement of the liver, spleen, gall bladder, pericardium, bone marrow, and mediastinal-paraaortic-intraceliac lymph nodes. T-cell receptor study of an autopsy specimen supported the diagnosis of PTCL that spread to the intraceliac organs and lymph nodes. We concluded that his pathogenicity progressed to a mixture of triple lymphoma as a result of double malignant transformations, which included PTCL from CLL, CD20-negative CLL, and CD20 positive DLBCL by Richter's transformation. Conclusions: Our case provides information on the biology of CLL, to transform from a low-grade chemosensitive status to a malignant chemoresistant status. PMID- 29796008 TI - Low incidence of pneumonia in COPD patients treated with inhaled corticosteroids undergoing pulmonary rehabilitation. AB - Background: Based on meta-analyses results, it is currently acknowledged that there is an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) undergoing inhaled corticosteroids (ICS) treatment. However, this is not found to be true in those with asthma. No data on this risk are available for COPD patients involved in pulmonary rehabilitation program (PR). Methods: For 1 year, we prospectively studied 2 cohorts of COPD patients undergoing PR and not undergoing PR. The first group included 438 patients undergoing PR of which 353 were treated with ICS, and 85 were treated with bronchodilators only. The second group was comprised of 76 COPD patients who were treated with ICS, but not PR. The control group consisted of 49 ICS-treated patients with asthma. The diagnosis of pneumonia, when suspected, had to be confirmed with a chest x-ray. Results: Overall, 6 cases of pneumonia were diagnosed in the first study group: 5 ICS-treated patients and 1 patient treated only with bronchodilators. This corresponded to a rate of 1.41 and 1.17%, respectively, compared to a rate of 6.6% in COPD patients not treated with PR, which was significantly higher (p = 0.029) than that in the first study group. No case of pneumonia was registered among patients with asthma. Conclusions: These findings suggest that a significantly lower incidence of pneumonia is found in COPD patients treated with ICS and PR than in patients treated with ICS but not with PR. This observation deserves to be investigated in large populations of PR treated COPD patients, possibly in multi-centric cohort studies. PMID- 29796009 TI - Regulation of IgE activity in inhalational tolerance via formation of IgG anti IgE/IgE immune complexes. AB - Background: Allergic asthma is an inflammatory disorder of the airways that results from inappropriate production of IgE against harmless, environmental antigens. Sequestration of free IgE using humanized IgG anti-IgE is an effective therapy for asthma and other atopic disorders. However, the status of free IgE in subjects who have naturally developed immune tolerance to inhaled antigens has not been well studied. Methods: C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) for 7 days to induce allergic airway disease (AAD) or 6 weeks to induce a state of local inhalational tolerance (LIT). Serum from AAD or LIT mice, diluted to achieve equivalent levels of total OVA-specific IgE, was used to sensitize rat basophil leukemia cells for allergen-mediated degranulation. Levels of degranulation were measured in relation to serum concentrations of free IgE and IgG anti-IgE/IgE immune complexes. Results: Serum from AAD animals induced a greater degree of basophil degranulation than serum from LIT animals. These results correlated with higher levels of free IgE in AAD animals, whereas LIT mice demonstrated a significant increase in IgG anti-IgE/IgE immune complexes relative to their diseased counterparts. Conclusions: Sequestration of free IgE by naturally occurring IgG anti-IgE may aid in the development of immune tolerance against inhaled allergens. The decrease in bioavailability of free IgE may, in turn, contribute to the overall reduction of asthma symptoms via a mechanism that mimics the therapeutic effects of humanized IgG anti-IgE. PMID- 29796010 TI - CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients. AB - Background: Endothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome. Methods: Peripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and - 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1alpha and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays. Results: EPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1alpha and Ang-2 were found in septic patients. SDF 1alpha showed a significant association with survival. Conclusions: Our data suggest that SDF-1alpha and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis. PMID- 29796012 TI - Accounting for equity considerations in cost-effectiveness analysis: a systematic review of rotavirus vaccine in low- and middle-income countries. AB - Background: Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs between total health gains and equity impacts of interventions. This study investigates to what extent equity considerations have been taken into account in CEA in low- and middle-income countries (LMICs), using rotavirus vaccination as a case study. Methods: Specific equity-related indicators for vaccination were first mapped to the Guidance on Priority Setting in Health Care (GPS-Health) checklist criteria. Economic evaluations of rotavirus vaccine in LMICs identified via a systematic review of the literature were assessed to explore the extent to which equity was considered in the research objectives and analysis, and whether it was reflected in the evaluation results. Results: The mapping process resulted in 18 unique indicators. Under the 'disease and intervention' criteria, severity of illness was incorporated in 75% of the articles, age distribution of the disease in 70%, and presence of comorbidities in 5%. For the 'social groups' criteria, relative coverage reflecting wealth based coverage inequality was taken into account in 30% of the articles, geographic location in 27%, household income level in 8%, and sex at birth in 5%. For the criteria of 'protection against the financial and social effects of ill health', age weighting was incorporated in 43% of the articles, societal perspective in 58%, caregiver's loss of productivity in 45%, and financial risk protection in 5%. Overall, some articles incorporated the indicators in their model inputs (20%) while the majority (80%) presented results (costs, health outcomes, or incremental cost-effectiveness ratios) differentiated according to the indicators. Critically, less than a fifth (17%) of articles incorporating indicators did so due to an explicit study objective related to capturing equity considerations. Most indicators were increasingly incorporated over time, with a notable exception of age-weighting of DALYs. Conclusion: Integrating equity criteria in CEA can help policy-makers better understand the distributional impact of health interventions. This study illustrates how equity considerations are currently being incorporated within CEA of rotavirus vaccination and highlights the components of equity that have been used in studies in LMICs. Areas for further improvement are identified. PMID- 29796013 TI - Delayed double reading of whole blood clotting test (WBCT) results at 20 and 30 minutes enhances diagnosis and treatment of viper envenomation. AB - Background: The whole blood clotting test (WBCT) is a simple test of coagulation that is often used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in sub-Saharan Africa. WBCT requires only a clean glass tube and several milliliters of venous blood and is ideal for use in poorly equipped health centers throughout the rural areas where 95% of snakebites occur. However, questions surrounding the accuracy and reliability of the test remain unanswered due to variations in testing conditions and a lack of comparative research with which to validate them. This is the first study to evaluate WBCT results at both 20-min (WBCT20) and 30-min (WBCT30) reading times in the same group of snakebite patients. Methods: In order to define the best reading time, the authors compared the results of serial WBCT evaluation at both 20 and 30 min after collection in 23 patients treated for snake envenomation in Bembereke, northern Benin. Results: WBCT results were identical at both reading times in patients without coagulopathy or when coagulation was restored permanently following a single dose of antivenom. Out of 17 patients with coagulopathy, 14 showed discrepancies between WBCT20 and WBCT30 results in at least one pair of serial evaluations. These could be completely contradictory results (e.g. normal clot at WBCT20 and no clot at WBCT30) or a marked difference in the quality of the clot (e.g. no clotting activity at WBCT20 and an unstable partial clot at WBCT30). WBCT discrepancies were encountered most frequently in three situations: initial normalization of hemostasis following antivenom therapy, detection of a secondary resumption of coagulopathy, or final restoration of hemostasis after a secondary resumption had occurred. Conclusions: This study suggests that the WBCT is robust and that a sequential reading should improve the diagnosis and monitoring of venom-induced coagulopathies. It also indicates the possibility of discrepancies in the sensitivity of WBCT20 and WBCT30 for detecting the resolution or reoccurrence of coagulopathy and identifies how these findings, if confirmed, may be used to increase the efficacy and efficiency of antivenom treatment in the field. PMID- 29796011 TI - Proteomic analysis of buccal gland secretion from fasting and feeding lampreys (Lampetra morii). AB - Background: Previous studies have shown that lamprey buccal glands contain some regulators related to anticoagulation, nociception, and immune responses due to the blood sucking habit. Regrettably, the protein expression profile in the buccal glands of feeding lampreys has never been reported yet. The present study was performed in order to further identify more proteins which are closely associated with lamprey feeding process. Methods: 2D-PAGE, NanoLC-MS/MS with higher resolution, Ensembl lamprey and NCBI protein databases, as well as western blot was used to compare the proteomics of buccal gland secretion from China northeast lampreys (Lampetra morii) which had been fed for 0, 10, and 60 min, respectively. Results: In the present study, the number of identified protein species in the buccal glands of feeding groups (60 min) was increased significantly, nearly ten times of that in the fasting group. During the feeding stage, novel proteins emerged in the buccal gland secretion of lampreys. According to gene ontology (GO) analysis and function predictions, these proteins were summarized and discussed based on their potential roles during feeding process. Furthermore, some of the identified proteins were confirmed to express during the feeding time of lampreys. Conclusion: When lampreys attack host fishes to suck blood and flesh, their buccal glands could secrete enough proteins to suppress blood coagulation, nociception, oxidative stress, immune response, as well as other adverse effects encountered during their parasitic lives. The present study would provide clues to clarify the feeding mechanism of the bloodsucking lampreys. PMID- 29796014 TI - Anodal tDCS over Primary Motor Cortex Provides No Advantage to Learning Motor Sequences via Observation. AB - When learning a new motor skill, we benefit from watching others. It has been suggested that observation of others' actions can build a motor representation in the observer, and as such, physical and observational learning might share a similar neural basis. If physical and observational learning share a similar neural basis, then motor cortex stimulation during observational practice should similarly enhance learning by observation as it does through physical practice. Here, we used transcranial direct-current stimulation (tDCS) to address whether anodal stimulation to M1 during observational training facilitates skill acquisition. Participants learned keypress sequences across four consecutive days of observational practice while receiving active or sham stimulation over M1. The results demonstrated that active stimulation provided no advantage to skill learning over sham stimulation. Further, Bayesian analyses revealed evidence in favour of the null hypothesis across our dependent measures. Our findings therefore provide no support for the hypothesis that excitatory M1 stimulation can enhance observational learning in a similar manner to physical learning. More generally, the results add to a growing literature that suggests that the effects of tDCS tend to be small, inconsistent, and hard to replicate. Future tDCS research should consider these factors when designing experimental procedures. PMID- 29796015 TI - Identification of Binding Partners of Deafness-Related Protein PDZD7. AB - PDZD7 is an important deafness gene, whose mutations are associated with syndromic and nonsyndromic hearing loss. PDZD7 contains multiple PDZ domains that are essential for organizing various proteins into protein complex. Several PDZD7 binding proteins have been identified, including usherin, ADGRV1, whirlin, harmonin, SANS, and MYO7A, all belonging to USH proteins. Here, we report the identification of novel PDZD7-binding partners through yeast two-hybrid screening using the first two PDZ domains of PDZD7 as bait. Eleven proteins were identified, most of which have not been reported as PDZD7-binding partners before. Among the identified proteins, ADGRV1, gelsolin, and beta-catenin have been shown to play important roles in hearing, whereas the functions of other proteins in the inner ear remain elusive. We confirmed the expression of one candidate PDZD7-binding protein, CADM1, in the mouse inner ear and evaluated the auditory function of Cadm1 knockout mice by performing auditory brainstem response (ABR) measurement. Unexpectedly, Cadm1 knockout mice show normal hearing threshold, which might be explained by the possible compensation by its homologs that are also expressed in the inner ear. Taken together, our work identified several novel PDZD7-binding proteins, which will help us to further understand the role of PDZD7 in hearing transduction. PMID- 29796016 TI - ERP and Behavioral Effects of Physical and Cognitive Training on Working Memory in Aging: A Randomized Controlled Study. AB - Working memory (WM) performance decreases with age. A promising method to improve WM is physical or cognitive training. The present randomized controlled study is aimed at evaluating the effects of different training methods on WM. A sample of 141 healthy older adults (mean age 70 years) was assigned to one of four groups: physical training, cognitive training, a social control group, and a no-contact control group. The participants trained for four months. Before and after the training, n-back task during an EEG recording was applied. The results show that cognitive training enhanced the target detection rate in the 2-back task. This was corroborated by an increased number of repeated digits in the backward digit span test but not in other memory tests. The improvement of WM was supported by an increased P3a prior to a correct target and an increased P3b both in nontarget and target trials. No ERP effects in the physical and no-contact control groups were found, while a reduction of P3a and P3b was found in the social control group. Thus, cognitive training enhances frontal and parietal processing related to the maintenance of a stored stimulus for subsequent matching with an upcoming stimulus and increases allocation of cognitive resources. These results indicate that multidomain cognitive training may increase WM capacity and neuronal activity in older age. PMID- 29796018 TI - Framework for Parallel Preprocessing of Microarray Data Using Hadoop. AB - Nowadays, microarray technology has become one of the popular ways to study gene expression and diagnosis of disease. National Center for Biology Information (NCBI) hosts public databases containing large volumes of biological data required to be preprocessed, since they carry high levels of noise and bias. Robust Multiarray Average (RMA) is one of the standard and popular methods that is utilized to preprocess the data and remove the noises. Most of the preprocessing algorithms are time-consuming and not able to handle a large number of datasets with thousands of experiments. Parallel processing can be used to address the above-mentioned issues. Hadoop is a well-known and ideal distributed file system framework that provides a parallel environment to run the experiment. In this research, for the first time, the capability of Hadoop and statistical power of R have been leveraged to parallelize the available preprocessing algorithm called RMA to efficiently process microarray data. The experiment has been run on cluster containing 5 nodes, while each node has 16 cores and 16 GB memory. It compares efficiency and the performance of parallelized RMA using Hadoop with parallelized RMA using affyPara package as well as sequential RMA. The result shows the speed-up rate of the proposed approach outperforms the sequential approach and affyPara approach. PMID- 29796019 TI - Cinnamon in Anticancer Armamentarium: A Molecular Approach. AB - In recent years, natural bioactive components draw a major attention for their potent anticarcinogenic activity. Cinnamon, one of the traditional spices, most frequently used in almost every household of tropical countries has got enormous efficacy to combat cancer. Cinnamon as a whole and/or its active components exhibited significant antineoplastic activity in different types of cancer. This review has been carried out to elicit the molecular mechanisms of action of cinnamon and its components on oncogenic regulators and related pathways. Web sites of Google Scholar, Medline, and PubMed were searched for articles written in English and published in peer-reviewed journals from 2003 to 2017. The anticarcinogenic potential of cinnamon varies with the type of cancer and also depends on the administered active compound individually or in combination with some chemicals or even extract of cinnamon as a whole. Some of its active components exert chemosensitization of well-known anticancer drugs. These outstanding properties of this spice necessitate its incorporation in both pharmaceuticals and nutraceuticals to explore possibilities of formulation of novel drug from this spice for treatment and prevention strategy of cancer. PMID- 29796017 TI - Changes in Resting-State Connectivity following Melody-Based Therapy in a Patient with Aphasia. AB - Melody-based treatments for patients with aphasia rely on the notion of preserved musical abilities in the RH, following left hemisphere damage. However, despite evidence for their effectiveness, the role of the RH is still an open question. We measured changes in resting-state functional connectivity following melody based intervention, to identify lateralization of treatment-related changes. A patient with aphasia due to left frontal and temporal hemorrhages following traumatic brain injuries (TBI) more than three years earlier received 48 sessions of melody-based intervention. Behavioral measures improved and were maintained at the 8-week posttreatment follow-up. Resting-state fMRI data collected before and after treatment showed an increase in connectivity between motor speech control areas (bilateral supplementary motor areas and insulae) and RH language areas (inferior frontal gyrus pars triangularis and pars opercularis). This change, which was specific for the RH, was greater than changes in a baseline interval measured before treatment. No changes in RH connectivity were found in a matched control TBI patient scanned at the same intervals. These results are compatible with a compensatory role for RH language areas following melody-based intervention. They further suggest that this therapy intervenes at the level of the interface between language areas and speech motor control areas necessary for language production. PMID- 29796020 TI - Soil-Transmitted Helminths in Top Soils Used for Horticultural Purposes in Cape Coast, Ghana. AB - This paper investigated the concentrations of eggs of three helminths (roundworm, hookworm, and whipworm) in the so-called black soils used for domestic and urban landscaping, home gardening and as growth medium for potted plants and pot experiments. The black soils are largely collected from active or abandoned waste dumpsites and fallowed or vegetated idle sites in the urban fringe or rural areas. Users buy black soils from dealers. Samples of black soils used for various purposes and at different places were collected for analysis of helminth eggs. The Modified EPA Method, which combines flotation and sedimentation, was used to isolate the eggs. The results show that these black soils have substantial loads of helminth eggs, with roundworm being dominant, followed by hookworm. Mean concentrations of helminth eggs were 2.45 (roundworm), 1.38 (hookworm), and 0.25 (whipworm) g-1 soil, respectively. The helminth egg loads also declined with duration of use of the black soils. It is concluded that black soils used for horticultural purposes in Ghana can be a potential source of helminth infestation. Therefore, treatment of black soils, regulation of black soil market and use, and development of growth media industry should be important components of helminth control strategy. PMID- 29796021 TI - Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma. AB - Background: The fractional exhaled nitric oxide (FeNO) and blood eosinophils are biomarkers of eosinophilic airway inflammation used in the diagnosis and management of asthma, although induced sputum is the gold standard test for phenotypic asthma. Nevertheless, the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils is controversial. Objective: To investigate the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils with uncontrolled asthmatic patients. It also examined the relationships between these biomarkers in bronchial reversibility and bronchial hyper-responsiveness (BHR). Methods: This study evaluated 75 uncontrolled asthmatic patients (symptom control and future risk of adverse outcomes). All patients underwent the following on the same day: FeNO, spirometry, BHR or bronchodilator reversibility, sputum induction and blood collection. Eosinophilic airway inflammation was defined as sputum eosinophils >= 2.5% or FeNO levels >= 32 parts per billion (ppb). Results: A significant positive relationship was between percentage of sputum eosinophils and FeNO (r = 0.4556; p < 0.0001) and percentage of blood eosinophils (r = 0.3647; p = 0.0013), and a significant negative correlation was between percentage of sputum neutrophils and FeNO (r = - 0.3653; p = 0.0013). No relationship between FeNO and percentage of blood eosinophils (p = 0.5801). ROC curve analysis identified FeNO was predictive of sputum eosinophilia [area under the curve (AUC) 0.707, p = 0.004] at a cutoff point of 35.5 ppb (sensitivity = 67.3%, specificity = 73.9%). Percentage of blood eosinophils was also highly predictive with an AUC of 0.73 (p = 0.002) at a cut-off point of 1.5%, sensitivity and specificity were 61.5 and 78.3%, respectively. Although the sputum neutrophil percentage was correlated with FeNO, ROC curve of these parameters did not show useful values (AUC = 0.297, p = 0.003; AUC = 0.295, p = 0.021). Conclusions and clinical relevance: Blood eosinophils and FeNO can accurately predict eosinophilic airway inflammation in uncontrolled asthmatic patients. FeNO is poor surrogates for sputum neutrophils and blood eosinophils. The FeNO level and blood eosinophils, which determine an optimal cutoff for sputum eosinophilia, need more studies. PMID- 29796023 TI - Translational Research in Pharmaceutical Sciences. PMID- 29796024 TI - The Effect of a Single Dose Oral Pregabalin on Hemodynamic Changes and Duration of Analgesia after Spinal Anesthesia in Orthopedic Surgeries of Tibial Fractures. AB - Treatment of acute pain and hemodynamic changes after surgery is extremely important. Various drugs for pain relief after surgery have been studied. The aim of this study was to evaluate the effect of a single dose of oral pregabalin on hemodynamic changes and duration of analgesia after spinal anesthesia in orthopedic surgeries of tibia fractures. This clinical trial was carried out on 120 patients with fractures of the tibia bone in 2014 in city of Zahedan. Sampling was conducted using randomized blocks and patients were placed into pregabalin (150 mg PO 1 h before anesthesia) and placebo groups. Duration of analgesia, severity of anxiety, mean arterial pressure, and pulse rate were evaluated in both groups. The mean age of the patients was 34.8 +/- 21.7 years and 84 patients (70%) were male and 36 (30%) were female. There were no significant differences at baseline characteristics of the patients in two arms of the study. After surgery, mean arterial pressure, pulse rate and anxiety, were significantly lower in intervention group. Also the duration of analgesia was significantly longer in intervention arm (185.3 +/- 4.9 vs 36.9 +/- 13.9, P < 0.01). Dizziness as a side effect of pregabalin was observed in 21 and 11 subjects in intervention and placebo groups, respectively (P < 0.01). The present study showed that a single dose of oral pregabalin increases the duration of analgesia and maintains hemodynamic stability in orthopedic surgery patients. PMID- 29796025 TI - Relationship between Serum Methadone Concentration and Cold Pressor Pain Sensitivity in Patients Undergoing Methadone Maintenance Therapy. AB - Hyperalgesia is a common clinical phenomenon among opioid dependent patients on methadone maintenance therapy (MMT) and it may be associated with undertreated pain and/or therapeutic failure. This study aimed to investigate association between serum methadone concentration (SMC) and cold pressor pain responses. Cold pressor pain responses in 147 opioid dependent patients on MMT were assessed using cold pressor test (CPT) at 0 h and at 2, 4, 8, 12, and 24 h after the dose intake. Blood samples were collected at 24 h after the dose. Serum methadone concentrations were measured using the Methadone ELISA kit and classified into two categories: < 400 ng/mL and >= 400 ng/mL. Eighty-eight patients (59.9%) had trough concentrations of < 400 ng/mL and 40.1% had trough concentrations of >= 400 ng/mL. There were significant effects of SMC on the cold pressor pain threshold (p = 0.019). Patients with concentrations < 400 ng/mL had significantly higher (almost 60% higher) cold pressor pain threshold (adjusted mean (95% CI) = 30.15 (24.29, 36.01) s) compared to those with concentrations of >= 400 ng/mL (18.93 (11.77, 26.08) seconds). There was also a 20% difference in pain tolerance, and 6% difference in cold pressor pain intensity score, neither of which were significant statistically (p > 0.05). Our results suggest an association of trough methadone concentration with the cold pressor pain threshold among opioid dependent patients on MMT. It would be useful to study the mechanisms underlying this association to help managing pain in such a population. PMID- 29796022 TI - Histone modifications and their role in epigenetics of atopy and allergic diseases. AB - This review covers basic aspects of histone modification and the role of posttranslational histone modifications in the development of allergic diseases, including the immune mechanisms underlying this development. Together with DNA methylation, histone modifications (including histone acetylation, methylation, phosphorylation, ubiquitination, etc.) represent the classical epigenetic mechanisms. However, much less attention has been given to histone modifications than to DNA methylation in the context of allergy. A systematic review of the literature was undertaken to provide an unbiased and comprehensive update on the involvement of histone modifications in allergy and the mechanisms underlying this development. In addition to covering the growing interest in the contribution of histone modifications in regulating the development of allergic diseases, this review summarizes some of the evidence supporting this contribution. There are at least two levels at which the role of histone modifications is manifested. One is the regulation of cells that contribute to the allergic inflammation (T cells and macrophages) and those that participate in airway remodeling [(myo-) fibroblasts]. The other is the direct association between histone modifications and allergic phenotypes. Inhibitors of histone modifying enzymes may potentially be used as anti-allergic drugs. Furthermore, epigenetic patterns may provide novel tools in the diagnosis of allergic disorders. PMID- 29796026 TI - A Systematic Review of Clinical Practice Guidelines for Castration-Resistant Prostate Cancer. AB - Cancer constitutes a huge burden on societies in countries with any level of economic development. Prostate cancer is the first most diagnosed cancer of men in developed countries and the forth one in developing countries in terms of incidence rate. It is also the third incident cancer of men in Iran along with a prevalence of about 10,000 cases. Castration-resistant prostate cancer (CRPC) is a severe stage of the disease with a number of newly discovered treatment options. These therapeutic alternatives including abiraterone acetate, enzalutamide, cabazitaxel, immunotherapy with sipuleucel-T, radiopharmaceuticals and bone-targeted therapies (zoledronic acid, denosumab) along with docetaxel have made the decision making process complex and challenging for clinicians. In addition to the challenges of selecting the best-fit treatment, high costs of new pharmaceuticals and technologies necessitates the health policy-makers to develop practice guidelines in adaptation with local resources and limitations. The aim of this paper is to review the clinical guidelines for the management of CRPC. For better comprehension of guideline recommendations, the main clinical trials on new treatments were also identified. The efficacy and safety outcomes including but not limited to overall survival, progression free survival, quality of life and adverse effects were summarized. The guidelines of American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EUA), Spanish Oncology Genitourinary Group (SOGG), Asian Oncology Summit, Saudi Oncology Society-Saudi Urology Association combined guideline, National Institute for Health and Care Excellence (NICE) and Canadian Urological Association-Canadian Urologic Oncology Group (CUA-CUOG) were covered in this paper. PMID- 29796027 TI - Effect of Combination Therapy of Methotrexate with Vitamin A in Patients with Low Risk GTN (Gestational Trophoblastic Neoplasia). AB - Methotrexate as a single agent chemotherapy in most women with low risk gestational trophoblastic neoplasia (GTN) has been associated with high treatment rate. Combination of methotrexate with Vitamin A due to reduced number of chemotherapy regime courses is one of the treatment options for patients with low risk GTN. Therefore, this study was performed with aim to determine the efficacy of combination therapy of Methotrexate with Vitamin A in low risk GTN treatment. This randomized clinical trial was performed on 49 patients with low risk gestational trophoblastic neoplasia. The treatment group (Group A = 19 cases) weekly received Methotrexate 50 mg/m2, and Vitamin A 200000 IU, intra-muscular, and the control group (Group B = 30 cases) only received Methotrexate 50 mg/m2 weekly. All patients were followed up for 8 weeks. Then, treatment outcomes were compared between two groups, and response to therapy was assessed in two groups by evaluation of HCG serum level. P < 0.05 was considered significant.Mean of B HCG serum level after 4 weeks in Group A and Group B was 68.5 mIu/mL and 360 mIu/mL, respectively (P = 0.018), and after 8 weeks was 1 mIu/mL and 12 mIu/mL, respectively (P = 0.074). Combination therapy of Methotrexate and Vitamin A in low risk GTN is associated with shorter duration of chemotherapy. PMID- 29796028 TI - Exposure to Antineoplastic Agents Induces Cytotoxicity in Nurse Lymphocytes: Role of Mitochondrial Damage and Oxidative Stress. AB - Cytotoxicity and mitochondrial parameters were studied in isolated lymphocytes and their mitochondria obtained from occupationally exposed nurses through inhalation exposure to antineoplastic drugs and results were compared to those of unexposed nurses. The group of occupationally exposed nurses consisted of 50 individuals ranging in age from 30 to 35 years. The control group included 50 nurses who were not occupationally exposed to the preparation and handling of antineoplastic drugs and their anthropometric and biochemical characteristics were similar to those of the expose group. All cytotoxicity and mitochondrial parameters evaluated in exposed group were significantly increased (P < 0.05) compared to the unexposed control group. Finally, the results of our study suggest that using antioxidant, mitochondrial and lysosomal protective agents can be promising drug candidates for the hospital staff in the risk of exposure to exposure to antineoplastic drugs. PMID- 29796029 TI - The Streptokinase Therapy Complications and its Associated Risk Factors in Patients with Acute ST Elevation Myocardial Infarction. AB - Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Despite the progress in the treatment of AMI, streptokinase is still being used in many countries. Because of the critical condition of patients with AMI and complications of streptokinase therapy, this study was performed to evaluate the pattern of adverse drug reaction (ADRs) induced by streptokinase and its associated risk factors in patients with acute ST elevation MI. A prospective cross-sectional study in a 14-month period was done at the university affiliated referral cardiovascular center. The Naranjo probability scale and Food and drug administration (FDA) criteria for severity of ADRs were performed for assessing the ADRs. The linear and logistic regression tests were used to evaluate the correlation between ADRs and study risk factors. During the study period, 217 patients who received streptokinase were entered. The majority of patients (n = 191) experienced at least one ADR. Six patients died in-hospital mainly because of cardiac causes. The history of drug allergy was the main predictor in occurring of ADRs (Odds ratio: 3.26; 95% CI: 1.48-457.6; p =0.026). The most serious ADR was hemorrhagic stroke with a 1.4% incidence. Hypotension was one of the most occurred ADR (n = 75). Anaphylactic shock was not detected in this study. In summary, our study showed that the history of drug allergy is the main predictor in occurring of ADRs by streptokinase. Furthermore, streptokinase therapy was associated with a higher rate of hemorrhagic stroke in Iranian population. PMID- 29796030 TI - The Availability and Affordability of Cardiovascular Medicines for Secondary Prevention in Tehran Province (Iran). AB - Availability and affordability of medicines are crucial to achieving success in prevention programs, particularly in developing countries. The aim of this study was to determine the availability and affordability of cardiovascular medicines for secondary prevention in Tehran province of Iran. A cross-sectional survey was conducted in Tehran province in 2015, using the 2nd edition of the World Health Organization/Health Action International methodology. Data on the availability and affordability of 21 selected cardiovascular medicines were collected from the public and private healthcare sectors. A total of 120 facilities were included in the survey and the medicines in this survey were both original and lowest-price generic. Lowest-price generic equivalent medicines were highly available (> 80%) in almost all pharmacies of both public and private sectors, while the availability of original brand medicines was highly poor in public and private pharmacies. The median price ratios were 0.72 to 0.76 for generic medicines. The treatment of cardiovascular diseases with lowest-price generic equivalent medicines was generally affordable; moreover, less than a single day's wage was adequate to purchase a month?s supply of the lowest priced generic of the surveyed medicines. The availability of the selected generic medicines for the secondary prevention of cardiovascular diseases is high in both public and private sectors and they were affordable for low-paid unskilled government workers in the province. The result of this study demonstrates that the supply policies pertaining to generic medicines have been implemented successfully. PMID- 29796031 TI - Vitamin D Deficiency Predicts the ST Elevation Type of Myocardial Infarction in Patients with Acute Coronary Syndrome. AB - According to studies, a significant association exists between the low levels of vitamin D and cardiovascular diseases such as myocardial infarction (MI). In a prospective case control study, 88 patients with acute coronary syndrome (ACS) including ST elevation myocardial infarction (STEMI) and Non-STEMI were enrolled. The plasma level of 25-hydroxy vitamin D [25(OH) D] was obtained at the time of acute MI. To assess the association between study variables logistic regression analysis was done. The overall rate of vitamin D deficiency was documented in 59.1% with the significantly higher prevalence rate in STEMI group (77.5% versus 43.7%; p = 0.001). In STEMI group, the plasma level of 25(OH) vitamin D was significantly lower than non-STEMI group (13.5 +/- 7.7 versus 24.3 +/- 14.9; p = 0.001). Vitamin D deficiency was the main predictor in occurring the ST elevation type of MI (Odd ratio: 8.1, 95% CI: 2.3 - 28.2; p = 0.001). The results of the present study demonstrated a higher prevalence of vitamin D deficiency among ACS patients. Furthermore, vitamin D deficiency was responsible for occurring ST elevation type of MI among ACS patients. Large studies are needed to confirm these findings. PMID- 29796032 TI - Prevalence and Antimicrobial Susceptibility Patterns of ESBL, AmpC and Carbapenemase-producing Enterobactericeae Isolated from Hospitalized Patients in Azerbaijan, Iran. AB - The current study was conducted to determine prevalence and antimicrobial susceptibility patterns, ESBL, AmpC and carbapenemase- producers among clinical isolates of Enterobacteriaceae. Three hundred and seven non-duplicative clinical isolates were collected from hospitalized patients in five medical centers in Azerbaijan, Iran. Initial screening for beta-lactamase production was performed using disc agar diffusion according to Clinical Laboratory Standards Institute (CLSI) guidelines. Phenotypic confirmatory tests was done using total ESBL/AmpC confirm kit, KPC/MBL and OXA-48 confirm kit according to manufacturer's instructions. The overall prevalence of ESBL, AmpC, and carbapenemase-producing strains were 42.7% (131/307), 14.0%(43/307) and 4.9% (15/307), respectively. The prevalence of ESBLs was 38.35%, 64.9% and 35.7% for E. coli, K. pneumoniae and E. cloacae, respectively. Carbapenemase activity was only observed among 15 K. pneumoniae isolates and detected phenotypes include MBL (9/57, 15.8%), KPC (4/57, 7.0%), and OXA-48 (2/57, 3.5%). Fourteen out of 307 isolates (4.6%) were recognized to have ESBL or AmpC hyper-producer with decreased cell wall permeability phenotype. All 4 shigella strains were positive for ESBL and 4 isolates of P. mirabilis, 2 isolates of M. morganii and 1 seratia spp. were detected as AmpC producer. The only C. freundii strain isolated was positive for both ESBL and AmpC. This study reveals high prevalence of multidrug-resistant (MDR) beta-lactamase-producing Enterobactericeae reaching 89.5%. Imipenem and meropenem showed potent antibacterial activities against all MDR beta-lactamase producers except for carbapenemase producers. After carbapenems, amikacin, piperacillin/tazobactam and amoxicillin/clavulanic acid were second the most effective drugs against beta-lactamase-producing E. coli isolates. PMID- 29796033 TI - Effect of Melissa officinalis (Lemon balm) on Sexual Dysfunction in Women: A Double- blind, Randomized, Placebo-controlled Study. AB - Hypoactive sexual desire disorder (HSDD) is the most prevalent female sexual dysfunction (FSD) and its bio-psychosocial multifactorial etiology justifies its multifaceted treatment. In Persian Medicine (PM), the weakness of the main organs (heart, brain and liver) is one of the important causes of lack of sexual desire; hence, their strengthening is a priority during treatment. Melissa officinalis is one of the medicinal plants with tonic characteristics for the main organs in PM and was used for treatment in this study. The aim of the present study was to evaluate the efficacy and safety of M. officinalis in the improvement of HSDD in women. Eighty nine (89) eligible women suffering from decreased sexual desire were randomly assigned to groups. The participants received medication (500 mg of aqueous extract of M. officinalis) or placebo 2 times a day for 4 weeks. Changes in scores of desire, arousal, lubrication, orgasm, satisfaction and pain were evaluated at the end of 4 weeks of treatment using the Female Sexual Function Index (FSFI) questionnaire in the two groups. Forty three participants completed the study. The increase in desire (P < 0.001), arousal (P < 0.001), lubrication (P < 0.005), orgasm (P < 0.001), satisfaction (P < 0.001), pain (P < 0.002) and FSFI total score (P < 0.001) in the M. officinalis group was significantly more than that of the placebo group. The willingness to continue treatment was significantly higher in the M. officinalis as compared to the placebo group (P < 0.001). M. officinalis may be a safe and effective herbal medicine for the improvement of HSDD in women. PMID- 29796034 TI - The Effect of Zizyphus Jujube Fruit Lotion on Breast Fissure in Breastfeeding Women. AB - Nipple fissure is a common problem during breastfeeding. Zizyphus Jujube Fruits is one of the oldest medicinal plants which can heal wounds through its antimicrobial and anti-inflammatory properties. This study aimed to determine the effect of jujube lotion on the recovery of breast fissure. This double-blind clinical trial recruited 100 primiparous lactating women who were randomly divided into two groups. In Jujube group, mothers used 0.5 mL of Fruit Lotion, and in control group mothers applied 4-5 drops of their breast milk five times a day, after breastfeeding. Both groups were examined on the 7th and 14th days after childbirth. The damage severity was assessed using the Amir scale and the presence or absence of nipple discharge was recorded. A significant difference was observed between the two groups in the extent of nipple damage before intervention on the 3rd day after childbirth and after intervention on the 7th and 14th days after childbirth (P = 0/02? P = 0/000). No significant difference was observed in sore nipple discharge between the two groups before the study and on the 7th day, while a statistically significant difference was observed between the two groups on the 14th day (P = 0/1, P = 0/01). The finding of this study revealed that the Zizyphus jujube fruits lotion heals nipple fissure faster and better than breast milk. PMID- 29796035 TI - The Effects of Berberis Vulgaris Juice on Insulin Indices in Women with Benign Breast Disease: A Randomized Controlled Clinical Trial. AB - The aim of this study was to investigate the effect of Berberis vulgaris (BV) juice consumption on insulin homeostasis, glycemic profiles of patients with benign breast disease (BBD). This parallel design, triple-blind, randomized and placebo controlled clinical trial was conducted on 85 eligible women diagnosed with BBD who recruited from Nour-Nejat hospital, Tabriz, Iran. Participants were randomly allocated into either intervention group who received BV juice (480 mL/day, n = 44) or BV juice placebo at the same time (480 mL/day, n = 41). After a 7 day run-in period, treatments were administered for the duration of 8 weeks. Participants, care givers and those who assessed laboratory analyses were blinded to the assignments (IRCT registry no: IRCT2012110511335N2). The relative treatment effects of BV supplementation showed decreased serum levels of insulin for 19%, C-peptide for 8%, homeostasis model assessment of insulin resistance index (HOMA-IR) for 16% and glucose to insulin ratio for 22% but HOMA-B increased 44% relative to placebo group over 8 weeks BV supplementation. Although these changes were not statistical significant, the mean changes for C-peptide and HOMA B were significant just after adjusting for baseline data and covariates. Administration of BV juice showed controlling effects on HOMA related indices, consequently might have beneficial effects on insulin signaling-related functions in women with benign breast tumor. PMID- 29796036 TI - Study of the Effect of Memantine on Negative Sign in Patients with Schizophrenia and Schizoaffective Disorders. AB - Memantine, an uncompetitive antagonist of glutamate receptor of the N-methyl-D aspartate type is approved for the treatment of moderate to severe Alzheimer disease (1). A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia (2). The aim of this study was to examine the efficacy and safety of memantine as an adjunctive treatment for antipsychotics in patient with psychopathology of schizophrenia and schizoaffective. In this study, we assessed the effect of memantine on the pro-inflammatory cytokines such as IL6, TNFalpha and CRP. In this double-blind, placebo-controlled study, participants were assigned to receive (5-20 mg/day) memantine (n = 29) or placebo (n = 29), in addition to continuing treatment with antipsychotic for 12 weeks. The primary efficacy measure was the level of pro-inflammatory cytokines (TNFA, IL6, CRP). Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse event (AEs), and measure of extrapyramidal symptoms. At end point, comparison of biomarkers (IL6, TNFalpha and CRP) in two groups before and after treatment showed a significant decrease of TNFalpha (P < 0.001), but the difference was not significant in CRP and IL6 level (p = 0.92 and p = 0.77, respectively). The frequency of serious AEs in the memantine vs. placebo group was similar. PMID- 29796037 TI - Effect of Vitamin B6 Versus Propranolol on Antipsychotic-Induced Akathisia: A pilot Comparative Double-blind Study. AB - Akathisia is a common adverse effect of antipsychotic drugs and is characterized by subjective feelings of restlessness. First-line treatment usually consists of propranolol, a beta adrenergic antagonist. However, propranolol does not seem to be efficacious in up to 70% of patients. This study was aimed to evaluate the effect of vitamin B6 versus propranolol on antipsychotic-induced akathisia (AIA). This study was a comparative, double-blind, randomized trial. In the present study, 66 adult patients with antipsychotic-induced akathisia were enrolled and randomized into three groups, and received vitamin B6 300 mg/12 h or 600 mg/12 h or propranolol 20 mg/12 h. The diagnosis of AIA was made by clinical examination and its severity was assessed by the Barnes Akathisia Rating Scale. Fifty one patients completed 5 days of the trial. The results showed that there was no significant difference in BARS score among the different groups which means that vitamin B6 attenuated the AIA similar to propranolol. However, there wasn't any significant difference between high or low dose of vitamin B6. In conclusion, the results of this trial suggest that vitamin B6 may be beneficial for ameliorating of antipsychotic-induced akathisia. PMID- 29796038 TI - Effect of Melatonin Administration on Sleep Quality in Sulfur Mustard Exposed Patients with Sleep Disorders. AB - Sulfur mustard (SM) is a toxic agent that targets several tissues. It is the leading cause of persistent lung disease, progressive deterioration in lung function, and mortality among injured patients. Disturbed sleep and poor quality of sleep are common in SM-exposed patients with chronic respiratory problems. Melatonin is an alternative medication that has been widely used to treat poor sleep quality caused by several specific conditions. This study aimed to evaluate the efficacy of melatonin administration in improvement of sleep quality in SM injured patients. In this randomized, double-blind and placebo-controlled trial study a total of 30 SM-exposed male patients were recruited. Patients received 3 mg melatonin (N = 15) or placebo (N = 15), orally in a single dose, 1 h before bedtime for 56 consecutive days. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnea was determined by STOP-Bang questionnaire. Compared with placebo, melatonin administration significantly improved global PSQI score, particularly sleep latency (P = 0.03) and subjective sleep quality (P = 0.004). Mean of global PSQI score was declined significantly (P = 0.01) from 10.13 +/- 3.44 to 6.66 +/- 3.08 in melatonin group. No differences in ESS and STOP-Bang scores were observed between two groups. Melatonin was effective in improving global PSQI score and sleep latency, but not daytime sleepiness and obstructive sleep apnea in SM-exposed patients. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients. PMID- 29796039 TI - Initial Results of a Prospective Study and Identification of New Strategies to Increase Traceability of Plasma-derived Medicines. AB - Plasma medicine is an innovative and emerging field used in a broad range of medical conditions. The present study focused on consumption and documentation pattern of plasma-derived medicines in a teaching hospital. A two-step study was conducted from October to December 2015. During the first phase, the patient records receiving plasma-derived medicines including Coagulation Factor VIII, IX, Prothrombin Complex Concentrate, Factor VIII/Von Wilberand Complex, Anti Hepatitis B Immunoglobulin, Intravenous Immunoglobulin, Anti-Tetanus Immunoglobulin, and Albumin were checked to assess recording details of these medications at the time of administration. Adverse events reported with the mentioned products were examined from traceability viewpoint. The second step concentrated on practical strategies to improve documentation status of plasma derived medicines in the hospital. We proposed national guideline as the first strategy and a new barcoding system to track and identify drug information of plasma medicines. Of the expected drug information, only generic name, dosage from, and strength were recorded after administration. Post-marketing safety surveillance of the plasma products was poor similarly. Unavailability of suitable instructions was the main reason for documentation deficiency. A guideline was designed and implemented to inform healthcare professionals about essentials of appropriate documentation for plasma-derived medicines. Updated results of the ongoing phase will be submitted soon. Our survey highlights the importance of documentation as a key component of plasma-derived medicines surveillance within the hospitals. PMID- 29796040 TI - Evaluation of Faculty and Non-faculty Physicians' Medication Errors in Outpatients' Prescriptions in Shiraz, Iran. AB - This study was aimed at finding the occurrence rate of prescription errors in the outpatients> prescriptions written by faculty and non-faculty physicians practicing in Shiraz, Iran. In this cross-sectional study 2000 outpatient prescriptions were randomly collected from pharmacies affiliated with Shiraz University of Medical Sciences (SUMS) and social security insurance in Shiraz, Iran. Patient information including age, weight, diagnosis and chief complain were recorded. Physicians 'characteristics were extracted from prescriptions. Prescription errors including errors in spelling, instruction, strength, dosage form and quantity as well as drug-drug interactions and contraindications were identified. The mean +/- SD age of patients was 37.91 +/- 21.10 years. Most of the patients were male (77.15%) and 81.50% of patients were adults. The average total number of drugs per prescription was 3.19 +/- 1.60. The mean +/- SD of prescription errors was 7.38 +/- 4.06. Spelling error (26.4%), instruction error (21.03%), and strength error (19.18%) were the most frequent prescription errors. The mean +/- SD of prescription errors was 7.83 +/- 4.2 and 6.93 +/- 3.88 in non faculty and faculty physicians, respectively (P < 0.05). Number of prescription errors increased significantly as the number of prescribed drugs increased. All prescriptions had at least one error. The rate of prescription errors was higher in non-faculty physicians. Number of prescription errors related with the prescribed drugs in the prescription. PMID- 29796041 TI - Medication Interaction and Physicians' Compliance Assessment through Medication Reconciliation Forms in a University Affiliated Hospital. AB - Medication interactions are associated with various unwanted adverse drug reactions. Medication Reconciliation involves a process in which a complete list of patient's previously prescribed medications are recorded and subsequently evaluated within the context of concomitantly prescribed medications and present medical condition during the hospitalization. Medical records of randomly selected 270 patients hospitalized in internal medicine, cardiovascular and infectious diseases wards were evaluated. Drug interactions were checked by LexiComp(r) database. Each interaction was assigned a risk rating of A, B, C, D, or X. The progression from A to X was based on increased urgency for responding to the data. Completed reconciliation forms were attached to patient charts for evaluation of physicians' compliance. Drug interactions were observed in 65.2% (176/270) of cases. The risk rating of interactions was categorized as C, D and X in 54.2%, 32.4%, and 13.4% of cases, respectively. There was a positive correlation between the number of prescribed medications and the rate of interactions (p-value < 0.001, Kendall's correlation coefficient = 0.487). Moreover, the length of hospitalization and the rate of drug interactions were significantly correlated (p-value < 0.001, Kendall's correlation coefficient = 0.350). Cardiovascular agents constituted the largest proportion of interactions (25%) followed by antibiotics (18%) and immunosuppressive agents (6%). In 59.6% of cases, no corrective action was taken by the physicians. Medication discrepancies occur commonly in hospital settings. Structured medication reconciliation may have a positive impact on prevention of medication errors. PMID- 29796042 TI - Assessment of Pharmacists Experiences and Attitudes Toward Professionalism and its Challenges in Pharmacy Practice. AB - Nowadays pharmacists should be involved in patients care and providing pharmaceutical care more than before, but still there is a gap between standard of care and pharmacy practice in pharmacies. In this study we aimed at evaluating the pharmacists experiences and attitudes about ethical professional practice in pharmacies. The study was conducted in the Tehran University of Medical Sciences, Tehran, Iran. This study performed as a mixed method study including 12 semi structured interviews and two focus group discussions (FGDs). All interviews and FGDs were recorded verbatim. The study evaluates the pharmacy practice based on the Code of Ethics for National Pharmaceutical System requirements. Our study presents the pharmacists ethical challenges in 14 areas of practice such as lack of proper pharmacists-patients and inter and intra-professional relationship; poor management of medication error; lack of pharmacists awareness about their responsibilities, professional rules and regulations; non-OTC drug dispensing without prescription; no collaboration with custodian organizations; dissatisfaction from profession; financial problems; mismanagement in confronting with ads and offers of pharmaceutical companies, and conflict of interest; and uneven drug distribution during shortage. For providing standard pharmaceutical care modification of infra structures, educational system and regulations in pharmaceutical system is highly recommended. PMID- 29796044 TI - Steroids in the Management of Synkinesis after Traumatic Oculomotor Palsy in India. AB - Traumatic oculomotor nerve palsies may result in aberrant regeneration and synkinesis that can impair normal facial function. We retrospectively investigated 16 patients with traumatic oculomotor nerve palsies who were treated with and without steroids to evaluate the rates of aberrant regeneration. The overall rates of aberrant regeneration were similar between the two groups and in line with other published series. Some limitations to our study may limit our ability to detect real differences, and additional studies would be beneficial. PMID- 29796043 TI - Similar rates of morphological evolution in domesticated and wild pigs and dogs. AB - Background: Whether the great morphological disparity of domesticated forms is the result of uniformly higher evolutionary rates compared to the wild populations is debated. We provide new data on changes of skull dimensions within historical time periods in wild and domesticated dogs and pigs to test if domestication might lead to an accelerated tempo of evolution in comparison to the wild conspecifics. Darwins and Haldanes were used to quantify evolutionary rates. Comparisons with evolutionary rates in other species and concerning other characteristics from the literature were conducted. Results: Newly gathered and literature data show that most skull dimensions do not change faster in domesticated breeds than in wild populations, although it is well known that there is extensive artificial selection on skull shape in some dog breeds. Evolutionary rates among domesticated forms and traits (e.g., production traits in pigs, and racing speed in some horses and greyhounds) might vary greatly with species and breeding aim. Conclusions: Our study shows that evolutionary rates in domestication are not in any event faster than those in the wild, although they are often perceived as such given the vast changes that appear in a relatively short period of time. This may imply that evolution under natural conditions - i.e., without human intervention - is not as slow as previously described, for example by Darwin. On the other hand, our results illustrate how diverse domestication is in tempo, mode, and processes involved. PMID- 29796046 TI - Evaluation of a Relative Afferent Pupillary Defect using the RAPDx(r) Device Before and After Treatment in Patients with Optic Nerve Disease. AB - We evaluated the amplitude and latency scores in the RAPDx(r) device together with other ophthalmic examinations, before and after treatment in four patients with optic nerve disease. In all patients, the visual acuity (VA) and visual field (VF) after treatment was resolved. Both scores after treatment were lower, with reduced laterality-based differences in VA and critical flicker fusion frequency (CFF). Even after treatment, 3 patients had laterality-based differences in circumpapillary retinal nerve fiber layer thickness (cpRFNLT). Both scores for evaluation of RAPD by RAPDx(r) correlated with subjective examinations and were useful for evaluation of the efficacy of treatment. PMID- 29796047 TI - Eyelid Myokymia with Concomitant Cerebral Tumour: A Case Report. AB - Eyelid myokymia is a localised movement disorder of the orbicularis oculi muscle with involuntary, fine, continuous, and undulating contractions. Although this entity is thought to be peripheral nerve origin, it rarely occurs with an intracranial lesion. The authors report a case of eyelid myokymia with concomitant cerebral tumour. A 52-year-old woman had a 6-month history of left eyelid myokymia accompanied by upper eyelid ptosis and lower eyelid reverse ptosis. Magnetic resonance imaging showed a solid mass measuring 20 * 25 * 20 mm in the temporal lobe of the cerebral cortex, showing isointense on T1-weighted and hyperintense on T2-weighted images. The clinical diagnosis was cerebral astrocytoma. PMID- 29796045 TI - Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer. AB - Relative afferent pupillary defects (RAPD) may be detected in patients with occipital lobe lesions. However, no previous report has used an objective technique to record the abnormal pupillary light reflex in such cases. Therefore, we measured the pupillary light reflex objectively in 15 patients with homonymous visual field defects (HVFD) due to occipital stroke using a new pupillometer. This study detected significantly smaller and slower pupillary light reflexes in the contralateral eyes than in the other eyes, which is equivalent to the presence of RAPD in patients with HVFDs caused by retrogeniculate lesions using an objective technique. Our results confirmed those of the previous reports using the swinging flashlight test more objectively. PMID- 29796048 TI - The Role of Botulinum Toxin in the Management of Ophthalmoplegia Secondary to Miller Fisher Syndrome. AB - Miller Fisher syndrome is an acute demyelinating polyneuropathy classically presenting with ataxia, areflexia, and ophthalmoplegia. The authors report the case of a 27-year-old female, who presented with limb weakness and double vision following a prodromal pharyngitis. Ophthalmic examination revealed fluctuant ophthalmoplegia eventually consistent with bilateral sixth cranial nerve palsies, prompting investigation for anti-ganglioside antibodies, which returned positive. Due to disabling diplopia, the patient was treated with botulinum toxin, with a resulting favourable reduction in the size of strabismus. Four months following her presentation, the patient was orthophoric and resumed normal activities. PMID- 29796049 TI - Basal Encephalocele Presenting with Bitemporal Hemianopsia in an Adult Male. AB - Basal encephaloceles are uncommon malformations that are usually congenital in nature, although, occasionally, they can be traumatic. When they are congenital, they are associated with skull and facial midline defects, central nervous system abnormalities, and possible ocular and visual problems. The authors present a case of an adult male with a basal encephalocele who presented with a bitemporal hemianopsia. Ocular abnormalities, visual loss, and visual field deficits have previously been reported in patients with basal encephalocele; however, there does not appear to be any reported cases with formal visual field testing to demonstrate specific defects such as a bitemporal hemianopsia. PMID- 29796050 TI - Angiographic Findings in the Tolosa-Hunt Syndrome and Resolution after Corticosteroid Treatment. AB - The Tolosa-Hunt syndrome is a rare clinical condition characterized by painful opthalmoparesis associated with idiopathic granulomatous inflammation of the orbital apex and cavernous sinus. Historically, this condition was thought to result from arteritic changes in the internal carotid artery and cavernous sinus. Modern digital angiographic techniques were unavailable when THS was initially described, and few reports exist on its high-resolution angiographic findings. Painful ophthalmoparesis, especially of the oculomotor nerve, warrants vascular imaging because of the concern for an underlying aneurysm. Here, we describe angiographic findings of THS which may be useful for clinicians when encountering patients presenting with painful ophthalmoplegia. PMID- 29796051 TI - Visual Function Improvement After Optic Nerve Sheath Fenestration in Osteopetrosis Patients with Optic Canal Stenosis: A Report of Two Cases. AB - The outcome of two patients with visual loss from osteopetrosis who underwent an optic nerve sheath fenestration (ONSF) is reported. A 20-year-old male and 26 year-old female with osteopetrosis had optic nerve edema. Computed tomography and magnetic resonance imaging demonstrated optic canals stenosis. Both patients underwent unilateral ONSF. After ONSF, the patients experienced improvement in visual acuity and optic nerve appearance. Therefore, when papilledema is recognized in osteopetrosis patients, it may be reasonable to start with an ONSF even if the optic canal seems to be stenotic because of the lower morbidity that is associated with this procedure compared with other surgical options. PMID- 29796052 TI - Pseudotumor Cerebri Syndrome with Resolution After Discontinuing High Vitamin A Containing Dietary Supplement: Case Report and Review. AB - A 24-year-old non-obese, but slightly overweight, female presented with a two week history of progressive severe headache associated with two days of blurry vision. Clinical exam was significant for bilateral papilledema and an enlarged blind spot on visual field testing. Contrast enhanced MRI head revealed no space occupying lesion. A lumbar puncture revealed an elevated opening pressure of 38 cm H2O with normal cerebrospinal fluid composition leading to a diagnosis of pseudotumor cerebri syndrome (PTCS). The patient lacked the typical risk factors of high body mass index or obvious antecedent medications; however, on subsequent questioning, she was chronically ingesting a high vitamin A containing weight loss dietary supplement (Thrive W(r) - Table 1), which we believe had caused intracranial hypertension. Discontinuation of the diet pill and treatment with acetazolamide led to marked improvement of her PTCS. This case highlights the fact that non-traditional products or medications with high vitamin A may cause pseudotumor cerebri, which treating physicians should assess for while dealing with non-obese PTCS patients. PMID- 29796053 TI - Ipilimumab-induced Adenohypophysitis and Orbital Apex Syndrome: Importance of Early Diagnosis and Management. AB - Ipilimumab is a novel anti-melanoma agent known to infrequently cause multi-organ autoimmunity. We report a case of pituitary hypophysitis and orbital inflammation followed by an orbital apex syndrome. A 64-year-old woman with a history of skin melanoma, receiving ipilimumab treatment, was seen for near total loss of vision in the right eye and proptosis. Headache of 3-month duration preceded the onset of diplopia followed by severe loss of vision in the right eye. Neuro ophthalmologic examination was consistent with an orbital apex syndrome. Extensive blood work and magnetic resonance imaging of the brain and orbit suggested an inflammatory process, rather than a metastatic lesion. Accordingly, the patient received high-dose methylprednisolone followed by tapering oral prednisone. At the 6-month follow-up visit, visual acuity on the right eye had significantly improved but diplopia remained, associated with large amplitude esotropia that improved incompletely though while on prednisone. The favourable outcome supported a final diagnosis of ipilimumab-induced inflammatory orbital apex syndrome and clinically silent pituitary adenohypophysitis. The case presented herein highlights unexpected ipilimumab-associated adverse effects and proposes the possibility of and interaction between inflammatory and immune mechanisms. PMID- 29796054 TI - Optical Coherence Tomography Characterization of Macular Changes Secondary to Arteriovenous Fistula. AB - Arteriovenous fistulas (AVFs) are abnormal shunts between the arterial and venous vascular systems. These usually produce ocular pain, increased intraocular pressure (IOP), and diplopia. Less frequently, they may cause retinal changes with visual impairment. Our purpose is to illustrate different retinal manifestations of AVF. We report the multimodal imaging study of three cases with retinal changes due to AVF, showing neurosensory retinal detachment, macular oedema, and macular ischemia. In conclusion, AVF may appear with different ophthalmic alterations. While usually increased IOP and diplopia are our main concerns, retinal study is mandatory, since a myriad of morphologic abnormalities might be present. PMID- 29796055 TI - Metastatic Melanoma of the Optic Nerve Sheath. AB - A 23-year-old man with a history of metastatic melanoma developed painful vision loss to counting fingers with enhancement of optic nerve on contrast-enhanced magnetic resonance imaging (MRI) and received a diagnosis of optic neuritis from an outside hospital. Despite empiric corticosteroid therapy, the patient worsened and developed secondary central retinal vein occlusion with further deterioration of vision. Repeat MRI demonstrated optic nerve sheath (ONS) involvement suggestive of optic perineuritis (OPN) and an ONS biopsy confirmed a rare case of isolated metastatic melanoma. Our case highlights the clinical and radiographic features that can mimic OPN and delay diagnosis and treatment. PMID- 29796056 TI - Diffusion-Weighted Magnetic Resonance Imaging in Acute Retinal Pathology. AB - The authors describe diffusion-weighted magnetic resonance imaging (DWI) as an accessible way to screen for acute retinal pathology in emergency setting. They describe three proof-of-principle patients who had abrupt onset of vision loss from acute retinal pathology where DWI was diagnostic. The deficits included central retinal artery occlusion and acute retinitis with retinal necrosis. DWI can be non-specific for aetiology, but it can rapidly localise the retinal pathology and initiate early therapeutic interventions in the emergency room. PMID- 29796057 TI - Perception and practice of breastfeeding in public in an urban community in Accra, Ghana. AB - Background: Reported stigmatization and confrontation (verbal and aggressive), of women when breastfeeding in public spaces constitutes a barrier to the recommendation to breastfeed infants on demand. While such stigma of breastfeeding in public has been reported more commonly in Western country media, there is no documented evidence of this stigma in developing country settings. The current study describes community perception and experience of breastfeeding in public in Accra, Ghana. A secondary objective is to explore factors associated with breastfeeding in public. Methods: A mixed methods design comprising a survey (n = 300), five Focus Group Discussions (FGD) with lactating women (n = 50), and nine In-Depth Interviews (IDI) with adult males (n = 5) and female health workers (n = 4) were also conducted. All data were collected between May and June, 2016 in the Ayawaso-West Sub-Metropolis, Accra. Data on sociodemographic characteristics; obstetric and breastfeeding history; and also perception, experience, and practice of breastfeeding in public, were collected. FGDs and IDI data were triangulated with survey data and presented using descriptive and analytical statistics and content analysis. Results: Majority of the survey respondents (92%) reported ever practicing breastfeeding in public. However, some reported feeling uncomfortable (52%), embarrassed (27%), or stigmatized (15%). Nevertheless, 72% of respondents felt they should be able to breastfeed anywhere. Almost all respondents (81%) reported covering their breasts when breastfeeding in public, and 70% felt private places should be used when they breastfed in public. Women in FGDs and IDI mentioned that they bottle feed their children in public places as a way to overcome the challenges of breastfeeding in public. Otherwise, they breastfeed in public because their children need to feed. Women were more likely to breastfeed in public if they reported support from a spouse (OR 3.99, 95% CI 1.50, 10.57) or other family members (OR 3.27, 95% CI 1.31, 8.18). Conclusions: Although women reported discomfort associated with breastfeeding in public, the practice is common. Awareness creation is needed to empower women to comfortably breastfeed and to sustain societal support of breastfeeding in public. PMID- 29796058 TI - Eg5 orchestrates porcine oocyte maturational progression by maintaining meiotic organelle arrangement. AB - Background: Kinesin superfamily proteins are microtubule-based molecular motors essential for the intracellular transport of various cargos, including organelles, proteins, and RNAs. However, their exact roles during mammalian oocyte meiosis have not been fully clarified. Results: Herein, we investigated the critical events during porcine oocyte meiotic maturation with the treatment of Eg5-specific inhibitor monastrol. We found that Eg5 inhibition resulted in oocyte meiotic failure by displaying the poor expansion of cumulus cells and reduced rate of polar body extrusion. In the meantime, the spindle assembly and chromosome alignment were compromised, accompanied by the decreased level of acetylated alpha-tubulin, indicative of less stable microtubules. Impaired actin dynamics and mitochondria integrity were also observed in Eg5-inhibited oocytes. Additionally, inhibition of Eg5 caused the abnormal distribution of cortical granules and ovastacin, a cortical granule component, potentially leading to the fertilization failure. Conclusions: Our findings reveal that Eg5 possesses an important function in porcine oocyte meiotic progression by regulating the organelle dynamics and arrangement. PMID- 29796059 TI - Lung Cancer Mortality in Tuscany from 1971 to 2010 and Its Connections with Silicosis: A Space-Cohort Analysis Based on Shared Models. AB - Lung cancer mortality in Tuscany (Italy) for males, from 1971 and 2010, is investigated. A hierarchical Bayesian model for space-time disease mapping is introduced. Such a model belongs to the class of shared random effect models and exploits the birth-cohort as the relevant time dimension. It allows for highlighting common and specific patterns of risk for each birth-cohort. The results show that different birth-cohorts exhibit quite different spatial patterns, even if the socioeconomic status is taken into account. In fact, there were different occupational exposures before and after the Second World War. The birth-cohort 1930-35 exhibits high relative risks related to particular areas. This fact could be connected with occupational exposure to risk factors for silicosis, perhaps a prognostic status for lung cancer. PMID- 29796060 TI - A Biologically Inspired Approach to Frequency Domain Feature Extraction for EEG Classification. AB - Classification of electroencephalogram (EEG) signal is important in mental decoding for brain-computer interfaces (BCI). We introduced a feature extraction approach based on frequency domain analysis to improve the classification performance on different mental tasks using single-channel EEG. This biologically inspired method extracts the most discriminative spectral features from power spectral densities (PSDs) of the EEG signals. We applied our method on a dataset of six subjects who performed five different imagination tasks: (i) resting state, (ii) mental arithmetic, (iii) imagination of left hand movement, (iv) imagination of right hand movement, and (v) imagination of letter "A." Pairwise and multiclass classifications were performed in single EEG channel using Linear Discriminant Analysis and Support Vector Machines. Our method produced results (mean classification accuracy of 83.06% for binary classification and 91.85% for multiclassification) that are on par with the state-of-the-art methods, using single-channel EEG with low computational cost. Among all task pairs, mental arithmetic versus letter imagination yielded the best result (mean classification accuracy of 90.29%), indicating that this task pair could be the most suitable pair for a binary class BCI. This study contributes to the development of single channel BCI, as well as finding the best task pair for user defined applications. PMID- 29796062 TI - A life less ordinary. PMID- 29796063 TI - Specialist not tertiary: Providing intensive care medicine in a district general hospital. PMID- 29796061 TI - Comparison of anti-HBV regimen with or without adefovir on hepatocellular carcinoma development of Chronic hepatitis B patients with compensated cirrhosis: a retrospective cohort study. AB - Background: The impact of different anti-virus regimens on prognosis of Chronic hepatitis B (CHB) related cirrhosis remains to be explored. We aim to investigate whether CHB-related HCC patients receiving nucleoside analogue regimen or not have a different prognosis. Methods: 242 CHB-related compensated cirrhosis patients from 2008 June to 2011 December were included in our study and attributed into groups based on their anti-virus regimens containing adefovir (ADV) or not. The clinical parameters and virological response between ADV containing regimen group and non-ADV containing regimen groups were reviewed and compared. The risk of hepatocellular carcinoma (HCC) development were analyzed and compared between two groups. Results: 127 patients received anti-virus regimen containing ADV and 115 patients received anti-virus regimen without ADV. The cumulative risk of HCC development among patients treated with ADV-contained therapy was significantly lower than that observed in patients with non-ADV contained therapy (p<0.05). Multivariate analysis indicated that ADV-containing regimen treatment was significantly associated with lower probability of HCC development, (hazard ratio, 0.18; 95% confidence interval range, 0.07-0.45, p<0.05). Conclusion: Both anti-virus regimens were effective in reducing serum HBV DNA. Regimen containing ADV decreased the incidence of HCC development in CHB patients with compensated cirrhosis. PMID- 29796064 TI - Cost of treating ventilator-associated pneumonia post cardiac surgery in the National Health Service: Results from a propensity-matched cohort study. AB - Background: Ventilator-associated pneumonia is associated with significant morbidity, mortality and healthcare costs. Most of the cost data that are available relate to general intensive care patients in privately remunerated institutions. This study assessed the cost of managing ventilator-associated pneumonia in a cardiac intensive care unit in the National Health Service in the United Kingdom. Methods: Propensity-matched study of prospectively collected data from the cardiac surgical database between April 2011 and December 2014 in all patients undergoing cardiac surgery (n = 3416). Patients who were diagnosed as developing ventilator-associated pneumonia, as per the surveillance definition for ventilator-associated pneumonia (n = 338), were propensity score matched with those who did not (n = 338). Costs of treating post-op cardiac surgery patients in intensive care and cost difference if ventilator-associated pneumonia occurred based on Healthcare Resource Group categories were assessed. Secondary outcomes included differences in morbidity, mortality and cardiac intensive care unit and in-hospital length of stay. Results: There were no significant differences in the pre-operative characteristics or procedures between the groups. Ventilator associated pneumonia developed in 10% of post-cardiac surgery patients. Post operatively, the ventilator-associated pneumonia group required longer ventilation (p < 0.01), more respiratory support, longer cardiac intensive care unit (8 vs 3, p < 0.001) and in-hospital stay (16 vs 9) days. The overall cost for post-operative recovery after cardiac surgery for ventilator-associated pneumonia patients was L15,124 compared to L6295 for non-ventilator-associated pneumonia (p < 0.01). The additional cost of treating patients with ventilator associated pneumonia was L8829. Conclusion: Ventilator-associated pneumonia was associated with significant morbidity to the patients, generating significant costs. This cost was nearer to the lower end for the cost for general intensive care unit patients in privately reimbursed systems. PMID- 29796065 TI - The Rule of Threes: three factors that triple the likelihood of families overriding first person consent for organ donation in the UK. AB - Between 1 April 2012 and 31 March 2015, 263 of the 2244 families in the UK whose loved ones had registered to donate organs for transplantation after their death on the NHS Organ Donor Register chose to override this decision; an override rate of 11.7%. Multivariable logistic regression analysis was applied to data relating to various aspects of the family approach in order to identify factors associated with such overrides. The factors associated with family overrides were failure to involve the Specialist Nurse for Organ Donation in the family approach (odds ratio 3.0), donation after circulatory death (odds ratio 2.7) and Black, Asian or Minority Ethnicity (odds ratio 2.7). This highlights the need to further engage with these groups in exploring donation as an end of life choice, and suggests that there may be, from the perspective of the family, fundamental differences between donation after brainstem death and circulatory death. It further adds to the body of data linking involvement of the Specialist Nurse for Organ Donation in the family approach to improved UK consent rates. PMID- 29796066 TI - The ultrasound neck imaging for tracheostomy study: A study prompting ultrasound screening prior to percutaneous tracheostomy procedures to improve patient outcomes. AB - Introduction: Percutaneous tracheostomy procedures are commonplace in intensive care units worldwide. Haemorrhagic complications, though potentially fatal, are thought to be under-reported. Ultrasonography use has not established itself in these procedures. This study assesses the prevalence and characteristics of pre tracheal blood vessels, to aid intensivists on potential procedural hazards. Method: A retrospective, observational study was performed in the UK. Computed tomography angiograms from January 2012 to October 2014 were randomly retrieved and analysed for vessel data. Results: A total of 343 adult patients were included (mean age: 65 (inter-quartile range 52-79), male: 63%). Forty-one percent of patients demonstrated a vessel overlying percutaneous tracheostomy insertion sites (C6-T1); veins were more common than arteries (69%, p = 0.001). Males were more likely to display veins (78 vs. 53%, p < 0.001). Discussion: A substantial proportion of patients exhibited pre-tracheal vessels. Front-of-neck ultrasonography has huge potential to identify these. Based on these data, we believe ultrasonography may be an effective screening tool for percutaneous tracheostomy procedures to reduce complications. Further research is required to study outcomes. PMID- 29796067 TI - A United Kingdom Register study of in-hospital outcomes of patients receiving extracorporeal carbon dioxide removal. AB - Introduction: Extracorporeal membrane carbon dioxide removal may have a role in treatment of patients with hypercapnic respiratory failure and refractory hypoxaemia and/or hypercapnia. Methods: We report on the use, outcomes and complications in United Kingdom intensive care units reporting patients on the Extracorporal Life Support Organisation register. Results: Of 60 patients, 42 (70%) had primarily hypoxic respiratory failure and 18 (30%) primarily hypercapnic respiratory failure. Use of veno-venous procedures increased compared to arterio-venous procedures. Following extracorporeal membrane carbon dioxide removal, ventilatory and blood gas parameters improved at 24 h. Twenty-seven (45%) of patients died before ICU discharge, while 27 (45%) of patients were discharged alive. The most common complications related to thrombosis or haemorrhage. Discussion: There is limited use of extracorporeal membrane carbon dioxide removal in UK clinical practice and outcomes reflect variability in indications and the technology used. Usage is likely to increase with the availability of new, simpler, technology. Further high quality evidence is needed. PMID- 29796068 TI - Discrepancies in measuring bladder volumes with bedside ultrasound and bladder scanning in the intensive care unit: A pilot study. AB - Objective: Intensive care unit patients are at risk for catheter-associated urinary tract infection. Earlier removal of catheters may be possible with accurate measurement of bladder volume. The purpose was to compare measured bladder volumes with bedside ultrasound, bladder scanner, and urine volume. Design: Prospective correlational descriptive study. Setting: Surgical/trauma intensive care unit and medical intensive care unit. Patients: Renal dialysis patients with less than 100 ml of urine in 24 h prior to urinary catheter removal and patients with suspected catheter obstruction. Measurements and main results: A physician trained in ultrasound and an advanced practice registered nurse trained in bladder scanning measured bladder volume; each blinded to the other's measurement. Device used first (ultrasound or bladder scanner) alternated daily. The intensive care unit team determined need for intermittent catheterization or treatment for suspected obstruction. Fifty-one measurements from 13 patients were obtained with results reported in milliliters. Ultrasound measurements were a mean volume of 72.1 +/- 127 (range: 1.7-666) and the bladder scanner measurements were 117 +/- 131 (0-529). On six occasions in five dialysis patients, urine volume measurement was available. The mean difference in ultrasound-urine volume mean difference was 0.5 +/- 37.8 (range: -68 to 38.2) and the bladder scanner urine volume was 132 +/- 167 (-72 to 397). Two patients with suspected catheter obstructions had ultrasound, bladder scanner, urine volume measurements, respectively: (1) 539, 51, >300 (began voiding before catheter replaced); (2) 666, 68, 1000 with catheter replacement. Conditions leading to greatest differences were obesity, indwelling catheter and ascites. Conclusions: These results demonstrate the inaccuracy of the bladder scanner. Ultrasound measurements appear more accurate. To remove urinary catheters in patients with minimal to low urine output, serial ultrasound measurements can be used to monitor bladder volumes and return of renal function. PMID- 29796069 TI - Barriers to the secondary use of data in critical care. AB - Purpose: We explore the challenges of the secondary use of data in clinical information systems which critical care units in the National Health Service (England) are facing. Methods: We conducted an online survey of critical care units in England regarding their practices in collecting and using clinical information systems and data. Results: Critical care units use clinical information systems typically independently of hospital information systems and focus mainly on using data for auditing, management reporting and research. Respondents reported that extracting data from their clinical information system was difficult and that they would use stored data more if it were easier to access. Data extraction takes time and who extracts data, the training they receive and the tools they use affect the extraction and use of data. Conclusion: A number of key challenges affect the secondary use of data in critical care: a lack of integration of information systems within critical care and across departments; barriers to accessing data; mismatched data tools and user requests. Data are predominantly used for reporting and research with less emphasis on using data to inform clinical practice. PMID- 29796070 TI - Retrospective analysis of cancer patients admitted to a tertiary centre with suspected neutropenic sepsis: Are C-reactive protein and neutrophil count useful prognostic biomarkers? AB - Historically, neutropenic sepsis has been associated with high mortality rates. However, there has been limited research into cancer patients admitted with suspected sepsis who are found to be non-neutropenic. C-reactive protein has been shown to be raised in cancer patients for reasons other than infection and there have been limited studies to look as its utility as a prognostic biomarker in suspected sepsis in this population. This study looked at 749 patients admitted to a tertiary cancer centre between January 2015 and February 2016 with suspected sepsis. The neutrophil count and C-reactive protein level was taken in all these patients on admission and at 72 h and compared to the primary outcome of 30-day all-cause mortality rates and hospital length of stay. There were 49 patients who died within 30 days (6.5%). Patients who died were found to have both higher neutrophil counts and C-reactive protein level on admission and at 72 h compared to survivors. Prolonged grade 4 neutropenia was shown to have higher mortality rates. There was only weak correlation between either neutrophil counts or C reactive protein level and length of hospital stay. This study suggests that higher C-reactive protein level and neutrophil counts and prolonged grade 4 neutropenia are associated with higher mortality rates in cancer patients admitted with suspected sepsis and have utility as prognostic biomarkers in this population. PMID- 29796071 TI - Reducing sound and light exposure to improve sleep on the adult intensive care unit: An inclusive narrative review. AB - Purpose: Sleep disturbance is common in intensive care units. It is associated with detrimental psychological impacts and has potential to worsen outcome. Irregular exposure to sound and light may disrupt circadian rhythm and cause frequent arousals from sleep. We sought to review the efficacy of environmental interventions to reduce sound and light exposure with the aim of improving patient sleep on adult intensive care units. Methods: We searched both PubMed (1966-30 May 2017) and Embase (1974-30 May 2017) for all relevant human (adult) studies and meta-analyses published in English using search terms ((intensive care OR critical care), AND (sleep OR sleep disorders), AND (light OR noise OR sound)). Bibliographies were explored. Articles were included if reporting change in patient sleep in response to an intervention to reduce disruptive intensive care unit sound /light exposure. Results: Fifteen studies were identified. Nine assessed mechanical interventions, four of which used polysomnography to assess sleep. Five studies looked at environmental measures to facilitate sleep and a further two (one already included as assessing a mechanical intervention) studied the use of sound to promote sleep. Most studies found a positive impact of the intervention on sleep. However, few studies used objective sleep assessments, sample sizes were small, methodologies sometimes imperfect and analysis limited. Data are substantially derived from specialist (neurosurgical, post-operative, cardiothoracic and cardiological) centres. Patients were often at the 'less sick' end of the spectrum in a variety of settings (open ward beds or side rooms). Conclusions: Simple measures to reduce intensive care unit patient sound/light exposure appear effective. However, larger and more inclusive high-quality studies are required in order to identify the measures most effective in different patient groups and any impacts on outcome. PMID- 29796072 TI - Advanced Critical Care Practitioners - Practical experience of implementing the Advanced Critical Care Practitioner Faculty of Intensive Care Medicine Curriculum in a London Critical Care Unit. AB - With a chronic shortage of doctors in intensive care, alternative roles are being explored. One of these is the role of the Advanced Critical Care Practitioner. The Advanced Critical Care Practitioner Curriculum was developed by the Faculty of Intensive Care Medicine and is used to provide a structured programme of training. The Advanced Critical Care Practitioner programme consists of an academic and clinical component. This article outlines a practical approach of how the programme was developed and is currently being delivered at a single institution. This new advanced practice role offers opportunities to fill gaps in the medical workforce, improve continuity of patient care, provide mentoring and training for less experienced staff as well as offering a rewarding clinical role. PMID- 29796073 TI - Classic cases revisited - Death of a nurse and the anatomy of error. AB - The tragic case of Mayra Cabrera who died as a result of wrong route drug administration is notable as it was the first time a verdict of unlawful killing was recorded against an NHS Trust. Error within medicine is a significant cause of patient morbidity and mortality. We explore the costs of error, the dynamics of error causation, the role of both the individual and institution in accountability for error, as well as transferrable lessons from other industries to reduce error. PMID- 29796074 TI - The life and work of Antonio Maria Valsalva (1666-1723) - Popping ears and tingling tongues. AB - The Valsalva manoeuvre is the increase in intra-thoracic pressure achieved by attempted expiration against a closed upper airway. The contraction of abdominal and other accessory muscles of respiration attempt to decrease the intra-thoracic volume, whilst the airway is closed either by the forceful apposition of the vocal cords or else by firmly closing the lips and sealing off the nose (e.g. by pinching it). Valsalva described this manoeuver as a way of checking the patency of the Eustachian tube. However, it has found other uses, including as a way to terminate episodes of supraventricular tachycardia and stopping ear popping-pain on high altitude flights. But who was Valsalva? PMID- 29796075 TI - An easily missed cause for low GCS in a Scottish Intensive Care Unit. AB - A case report of a 36-year-old patient who presented with seizures, a large thyroid and decreased consciousness level requiring admission to the intensive care unit, where the final diagnosis had a prevalence of 2.1/100,000 and a female to male ratio of 4:1. The final diagnosis was suggested early by a focussed internet search. This is unusual because as clinicians we often tell the general public to ignore an internet search. The early suggestion demonstrated that in the right hands the use of internet searches can help us make more informed decisions and aid patient management when combined with traditional investigative medical practice. However, the lesson with this case is that there are many unusual and rare causes of presentations to critical care units and as clinicians we should keep an open mind and wide differential diagnosis so as not to miss the rarer reasons for these presentations. PMID- 29796077 TI - Low tidal volume ventilation. PMID- 29796076 TI - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids with seizures and central pyrexia, in a patient requiring tracheal intubation and mechanical ventilation: A case report. AB - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) has been described in multiple case reports since it was first described in the literature in 2010. The patient described is a 54-year-old man with no significant medical history who presented with ataxia, diplopia and hearing and taste disturbances. His GCS reduced to the point at which he required intubation and he was treated for 50 days on an intensive care unit. The patient's course also includes seizures, first described in 2014, and central pyrexia, which has not been previously described in case reports of CLIPPERS. Intravenous methylprednisolone resulted in a rapid and significant recovery; neurological rehabilitation is ongoing 10 months from diagnosis. The importance of recognition of unusual radiological findings and rapid treatment cannot be overemphasised in improving patient's long-term outcomes. PMID- 29796078 TI - Targeted bedside echocardiography in the management of critically ill patients. PMID- 29796080 TI - May the force be with you. PMID- 29796079 TI - Lessons from lung ultrasound. PMID- 29796081 TI - A factor analytic investigation of DSM-5 PTSD symptoms in a culturally diverse sample of refugees resettled in Australia. AB - Background: Refugees and asylum-seekers are often exposed to multiple types of potentially traumatic events (PTEs) and report elevated rates of psychological disorders, including posttraumatic stress disorder (PTSD). Considering this, refugee populations merit continued research in the field of traumatic stress to better understand the psychological impact of these experiences. The symptom structure of PTSD underwent a major revision in the recent formulation in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM 5), and this reformulation has yet to be comprehensively investigated in the context of PTSD arising from traumatic events experienced by refugees. The current study assessed the construct validity of the DSM-5 PTSD structure in a refugee sample from a variety of cultural backgrounds alongside four alternate models commonly identified in western populations, namely the four-factor Dysphoria model, the five-factor Dysphoric Arousal model, and the six-factor Anhedonia and Externalising Behaviours models. Methods: A total of 246 refugees settled in Australia were assessed using the Harvard Trauma Questionnaire, to measure exposure to potentially traumatic events (PTEs), and the Posttraumatic Diagnostic Scale, to assess symptoms of PTSD based on DSM-5 criteria. All measures were translated into Arabic, Farsi or Tamil using rigorous translation procedures, or provided in English. Results: Findings from five confirmatory factor analyses (CFAs) revealed that all models demonstrated acceptable model fit. However, an examination of relative fit revealed that the DSM-5 model provided the poorest fit overall for our sample. Instead, we found preliminary evidence in support of the six-factor Anhedonia model, comprising the symptom clusters of re-experiencing, avoidance, negative affect, anhedonia, dysphoric arousal and anxious arousal, as the superior model for our data. Conclusions: Our findings offer preliminary support for the applicability of the Anhedonia model to a culturally diverse refugee sample, and contribute to a growing body of studies which indicate that the DSM-5 model may not best represent the symptom structure of PTSD found across non-western conflict-affected populations. PMID- 29796082 TI - Towards Subject-Specific Strength Training Design through Predictive Use of Musculoskeletal Models. AB - Lower extremity dysfunction is often associated with hip muscle strength deficiencies. Detailed knowledge of the muscle forces generated in the hip under specific external loading conditions enables specific structures to be trained. The aim of this study was to find the most effective movement type and loading direction to enable the training of specific parts of the hip muscles using a standing posture and a pulley system. In a novel approach to release the predictive power of musculoskeletal modelling techniques based on inverse dynamics, flexion/extension and ab-/adduction movements were virtually created. To demonstrate the effectiveness of this approach, three hip orientations and an external loading force that was systematically rotated around the body were simulated using a state-of-the art OpenSim model in order to establish ideal designs for training of the anterior and posterior parts of the M. gluteus medius (GM). The external force direction as well as the hip orientation greatly influenced the muscle forces in the different parts of the GM. No setting was found for simultaneous training of the anterior and posterior parts with a muscle force higher than 50% of the maximum. Importantly, this study has demonstrated the use of musculoskeletal models as an approach to predict muscle force variations for different strength and rehabilitation exercise variations. PMID- 29796083 TI - Identification of two integration sites in favor of transgene expression in Trichoderma reesei. AB - Background: The ascomycete fungus Trichoderma reesei was widely used as a biotechnological workhorse for production of cellulases and recombinant proteins due to its large capacity of protein secretion. Transgenesis by random integration of a gene of interest (GOI) into the genome of T. reesei can generate series of strains that express different levels of the indicated transgene. The insertion site of the GOI plays an important role in the ultimate production of the targeted proteins. However, so far no systematic studies have been made to identify transgene integration loci for optimal expression of the GOI in T. reesei. Currently, only the locus of exocellobiohydrolases I encoding gene (cbh1) is widely used as a promising integration site to lead to high expression level of the GOI. No additional sites associated with efficient gene expression have been characterized. Results: To search for gene integration sites that benefit for the secreted expression of GOI, the food-and-mouth disease virus 2A protein was applied for co-expression of an Aspergillus niger lipA gene and Discosoma sp. DsRed1 gene in T. reesei, by random integration of the expression cassette into the genome. We demonstrated that the fluorescent intensity of RFP (red fluorescent protein) inside of the cell was well correlated with the secreted lipase yields, based on which, we successfully developed a high-throughput screening method to screen strains with relatively higher secreted expression of the GOI (in this study, lipase). The copy number and the insertion sites of the transgene were investigated among the selected highly expressed strains. Eventually, in addition to cbh1 gene locus, two other genome insertion loci that efficiently facilitate gene expression in T. reesei were identified. Conclusions: We have successfully developed a high-throughput screening method to screen strains with optimal expression of the indicated secreted proteins in T. reesei. Moreover, we identified two optimal genome loci for transgene expression, which could provide new approach to modulate gene expression levels while retaining the indicated promoter and culture conditions. PMID- 29796084 TI - Integrated experimental and technoeconomic evaluation of two-stage Cu-catalyzed alkaline-oxidative pretreatment of hybrid poplar. AB - Background: When applied to recalcitrant lignocellulosic feedstocks, multi-stage pretreatments can provide more processing flexibility to optimize or balance process outcomes such as increasing delignification, preserving hemicellulose, and maximizing enzymatic hydrolysis yields. We previously reported that adding an alkaline pre-extraction step to a copper-catalyzed alkaline hydrogen peroxide (Cu AHP) pretreatment process resulted in improved sugar yields, but the process still utilized relatively high chemical inputs (catalyst and H2O2) and enzyme loadings. We hypothesized that by increasing the temperature of the alkaline pre extraction step in water or ethanol, we could reduce the inputs required during Cu-AHP pretreatment and enzymatic hydrolysis without significant loss in sugar yield. We also performed technoeconomic analysis to determine if ethanol or water was the more cost-effective solvent during alkaline pre-extraction and if the expense associated with increasing the temperature was economically justified. Results: After Cu-AHP pretreatment of 120 degrees C NaOH-H2O pre-extracted and 120 degrees C NaOH-EtOH pre-extracted biomass, approximately 1.4-fold more total lignin was solubilized (78% and 74%, respectively) compared to the 30 degrees C NaOH-H2O pre-extraction (55%) carried out in a previous study. Consequently, increasing the temperature of the alkaline pre-extraction step to 120 degrees C in both ethanol and water allowed us to decrease bipyridine and H2O2 during Cu AHP and enzymes during hydrolysis with only a small reduction in sugar yields compared to 30 degrees C alkaline pre-extraction. Technoeconomic analysis indicated that 120 degrees C NaOH-H2O pre-extraction has the lowest installed ($246 million) and raw material ($175 million) costs compared to the other process configurations. Conclusions: We found that by increasing the temperature of the alkaline pre-extraction step, we could successfully lower the inputs for pretreatment and enzymatic hydrolysis. Based on sugar yields as well as capital, feedstock, and operating costs, 120 degrees C NaOH-H2O pre-extraction was superior to both 120 degrees C NaOH-EtOH and 30 degrees C NaOH-H2O pre extraction. PMID- 29796085 TI - Determination of optimal biomass pretreatment strategies for biofuel production: investigation of relationships between surface-exposed polysaccharides and their enzymatic conversion using carbohydrate-binding modules. AB - Background: Pretreatment of lignocellulosic biomass (LCB) is a key step for its efficient bioconversion into ethanol. Determining the best pretreatment and its parameters requires monitoring its impacts on the biomass material. Here, we used fluorescent protein-tagged carbohydrate-binding modules method (FTCM)-depletion assay to study the relationship between surface-exposed polysaccharides and enzymatic hydrolysis of LCB. Results: Our results indicated that alkali extrusion pretreatment led to the highest hydrolysis rates for alfalfa stover, cattail stems and flax shives, despite its lower lignin removal efficiency compared to alkali pretreatment. Corn crop residues were more sensitive to alkali pretreatments, leading to higher hydrolysis rates. A clear relationship was consistently observed between total surface-exposed cellulose detected by the FTCM-depletion assay and biomass enzymatic hydrolysis. Comparison of bioconversion yield and total composition analysis (by NREL/TP-510-42618) of LCB prior to or after pretreatments did not show any close relationship. Lignin removal efficiency and total cellulose content (by NREL/TP-510-42618) led to an unreliable prediction of enzymatic polysaccharide hydrolysis. Conclusions: Fluorescent protein-tagged carbohydrate-binding modules method (FTCM)-depletion assay provided direct evidence that cellulose exposure is the key determinant of hydrolysis yield. The clear and robust relationships that were observed between the cellulose accessibility by FTCM probes and enzymatic hydrolysis rates change could be evolved into a powerful prediction tool that might help develop optimal biomass pretreatment strategies for biofuel production. PMID- 29796086 TI - Effect of oxygen mass transfer rate on the production of 2,3-butanediol from glucose and agro-industrial byproducts by Bacillus licheniformis ATCC9789. AB - Background: 2,3-Butanediol (BD) is a largely used fossil-based platform chemical. The yield and productivity of bio-based BD fermentative production must be increased and cheaper substrates need to be identified, to make bio-based BD production more competitive. As BD bioproduction occurs under microaerobic conditions, a fine tuning and control of the oxygen transfer rate (OTR) is crucial to maximize BD yield and productivity. Very few studies on BD bioproduction focused on the use of non-pathogenic microorganisms and of byproducts as substrate. The goal of this work was to optimize BD bioproduction by the non-pathogenic strain Bacillus licheniformis ATCC9789 by (i) identifying the ranges of volumetric and biomass-specific OTR that maximize BD yield and productivity using standard sugar and protein sources, and (ii) performing a preliminary evaluation of the variation in process performances and cost resulting from the replacement of glucose with molasses, and beef extract/peptone with chicken meat and bone meal, a byproduct of the meat production industry. Results: OTR optimization with an expensive, standard medium containing glucose, beef extract and peptone revealed that OTRs in the 7-15 mmol/L/h range lead to an optimal BD yield (0.43 +/- 0.03 g/g) and productivity (0.91 +/- 0.05 g/L/h). The corresponding optimal range of biomass-specific OTR was equal to 1.4-7.9 [Formula: see text], whereas the respiratory quotient ranged from 1.8 to 2.5. The switch to an agro-industrial byproduct-based medium containing chicken meat and bone meal and molasses led to a 50% decrease in both BD yield and productivity. A preliminary economic analysis indicated that the use of the byproduct-based medium can reduce by about 45% the BD production cost. Conclusions: A procedure for OTR optimization was developed and implemented, leading to the identification of a range of biomass-specific OTR and respiratory quotient to be used for the scale-up and control of BD bioproduction by Bacillus licheniformis. The switch to a byproduct-based medium led to a relevant decrease in BD production cost. Further research is needed to optimize the process of BD bioproduction from the tested byproduct-based medium. PMID- 29796089 TI - A novel technique of harmonic tissue dissection reduces seroma formation after modified radical mastectomy compared to conventional electrocautery: a single blind randomized controlled trial. AB - Background: Seroma is the most frequent postoperative complication following breast cancer surgery. Our aim was to evaluate the effect of the harmonic focus scalpel versus electrocautery in reducing seroma formation post-mastectomy and axillary clearance. Methods: A prospective randomized controlled trial study was conducted at the Department of Surgery of Suez Canal University Hospital from April 26th 2014 to 30th June 2016. Seventy-two women, in whom a mastectomy and axillary clearance for breast cancer were performed, were randomly allocated to either harmonic dissection (n = 36) or electrocautery (n = 36). Results: The mean operative time was significantly longer for harmonic dissection compared with electrocautery (2.63 +/- 0.41 vs. 1.75 +/- 0.26 h; p < 0.0001). In addition, a significantly smaller amount of intraoperative blood loss (69.4 +/- 25.1 vs. 255.5 +/- 41.6 ml; p = 0.002) and total drainage volume (1277.8 +/- 172.5 ml vs. 3300 +/- 167.5 ml; p = 0.002) were found in the harmonic group. Moreover, there was a significant reduction in the time of drain removal (10.9 +/- 1.12 vs. 15.9 +/- 1.44; p = 0.001) and the incidence of seroma formation after drain removal [8.3% vs 33.3%; p = 0.003] in the harmonic group compared with those in the electrocautery group. Conclusion: Harmonic dissection technique leads to significant decreases in intraoperative blood loss, total drainage volume and postoperative seroma in terms of shorter drain duration with a minimal increase in the operative time and better quality of life. Here, we recommend the use of the harmonic dissection technique in mastectomy and axillary clearance. PMID- 29796088 TI - Yeast lipids from cardoon stalks, stranded driftwood and olive tree pruning residues as possible extra sources of oils for producing biofuels and biochemicals. AB - Background: Some lignocellulosic biomass feedstocks occur in Mediterranean Countries. They are still largely unexploited and cause considerable problems due to the lack of cost-effective harvesting, storage and disposal technologies. Recent studies found that some basidiomycetous yeasts are able to accumulate high amount of intracellular lipids for biorefinery processes (i.e., biofuels and biochemicals). Accordingly, the above biomass feedstocks could be used as carbon sources (after their pre-treatment and hydrolysis) for lipid accumulation by oleaginous yeasts. Results: Cardoon stalks, stranded driftwood and olive tree pruning residues were pre-treated with steam-explosion and enzymatic hydrolysis for releasing free mono- and oligosaccharides. Lipid accumulation tests were performed at two temperatures (20 and 25 degrees C) using Leucosporidium creatinivorum DBVPG 4794, Naganishia adeliensis DBVPG 5195 and Solicoccozyma terricola DBVPG 5870. S. terricola grown on cardoon stalks at 20 degrees C exhibited the highest lipid production (13.20 g/l), a lipid yield (28.95%) close to the maximum theoretical value and a lipid composition similar to that found in palm oil. On the contrary, N. adeliensis grown on stranded driftwood and olive tree pruning residues exhibited a lipid composition similar to those of olive and almonds oils. A predictive evaluation of the physical properties of the potential biodiesel obtainable by lipids produced by tested yeast strains has been reported and discussed. Conclusions: Lipids produced by some basidiomycetous yeasts grown on Mediterranean lignocellulosic biomass feedstocks could be used as supplementary sources of oils for producing biofuels and biochemicals. PMID- 29796087 TI - Use of bacteria for improving the lignocellulose biorefinery process: importance of pre-erosion. AB - Background: Biological pretreatment is an important alternative strategy for biorefining lignocellulose and has attracted increasing attention in recent years. However, current designs for this pretreatment mainly focus on using various white rot fungi, overlooking the bacteria. To the best of our knowledge, for the first time, we evaluated the potential contribution of bacteria to lignocellulose pretreatment, with and without a physicochemical process, based on the bacterial strain Pandoraea sp. B-6 (hereafter B-6) that was isolated from erosive bamboo slips. Moreover, the mechanism of the improvement of reducing sugar yield by bacteria was elucidated via analyses of the physicochemical changes of corn stover (CS) before and after pretreatment. Results: The digestibility of CS pretreated with B-6 was equivalent to that of untreated CS. The recalcitrant CS surface provided fewer mediators for contact with the extracellular enzymes of B-6. A pre-erosion strategy using a tetrahydrofuran water co-solvent system was shown to destroy the recalcitrant CS surface. The optimal condition for pre-erosion showed a 6.5-fold increase in enzymatic digestibility compared with untreated CS. The pre-erosion of CS can expose more phenolic compounds that were chelated to oxidized Mn3+ and also provided mediators for combination with laccase, which was attributable to B-6 pretreatment. B-6 pretreatment following pre-erosion exhibited a sugar yield that was 91.2 mg/g greater than that of pre-erosion alone and 7.5-fold higher than that of untreated CS. This pre-erosion application was able to destroy the recalcitrant CS surface, thus leading to a rough and porous architecture that better facilitated the diffusion and transport of lignin derivatives. This enhanced the ability of laccase and manganese peroxidase secreted by B-6 to improve the efficiency of this biological pretreatment. Conclusion: Bacteria were not found useful alone as a biological pretreatment, but they significantly improved enzymatic digestion after lignocellulose breakdown via other physicochemical methods. Nonetheless, phenyl or phenoxy radicals were used by laccase and manganese peroxidase in B-6 for lignin attack or lignin depolymerization. These particular mediators released from the recalcitrance network of lignocellulose openings are important for the efficacy of this bacterial pretreatment. Our findings thus offer a novel perspective on the effective design of biological pretreatment methods for lignocellulose. PMID- 29796091 TI - Preventing sepsis in health care - It's in your hands: A World Health Organization call to action. PMID- 29796090 TI - Predictors of hydrocephalus as a complication of non-traumatic subarachnoid hemorrhage: a retrospective observational cohort study in 107 patients. AB - Background: The predictors of shunt dependency such as amount of subarachnoid blood, acute hydrocephalus (HC), mode of aneurysm repair, clinical grade at admission and cerebro spinal fluid (CSF) drainage in excess of 1500 ml during the 1st week after the subarachnoid hemorrhage (SAH) have been identified as predictors of shunt dependency. Therefore our main objective is to identify predictors of CSF shunt dependency following non-traumatic subarachnoid hemorrhage. Methods: We performed a retrospective study including patients from January 1st 2012 to September 30th 2014 between 16 and 89 years old and had a non traumatic subarachnoid hemorrhage in cranial computed tomography (CCT). We excluded patients with the following characteristics: Patients who died 3 days after admittance, lesions in brainstem, previous surgical treatment in another clinic, traumatic brain injury, pregnancy and disability prior to SAH.We performed a descriptive and comparative analysis as well as a logistic regression with the variables that showed a significant difference (p < 0.05). Hence we identified the variables concerning HC after non traumatic SAH and its correlation. Results: One hundred and seven clinical files of patients with non traumatic SAH were analyzed. Twenty one (48%) later underwent shunt treatment. Shunt patients had significantly clinical and corroborated with doppler ultrasonography vasospasmus (p = 0.015), OR = 5.2. The amount of subarachnoidal blood according to modified Fisher grade was (p = 0.008) OR = 10.9. Endovascularly treated patients were less often shunted as compared with those undergoing surgical aneurysm repair (p = 0.004). Conclusion: Vasospasmus and a large amount of ventricular blood seem to be a predictor concerning hydrocephalus after non-traumatic SAH. Hence according to our results the presence of these two variables could alert the treating physician in the decision whether an early shunt implantation < 7 days after SAH should be necessary. PMID- 29796092 TI - Interventions to improve hand hygiene compliance in patient care: Reflections on three systematic reviews for the Cochrane Collaboration 2007-2017. AB - This article presents highlights from a recently updated systematic Cochrane review evaluating the effectiveness of interventions to improve hand hygiene compliance in patient care. It is an advance on the two earlier reviews we undertook on the same topic as it has, for the first time, provided very rigorous synthesis of evidence that such interventions can improve practice. In this article, we provide highlights from a recently updated Cochrane systematic review. We identify omissions in the information reported and point out important aspects of hand hygiene intervention studies that were beyond the scope of the review. A full report of the review is available free of charge on the Cochrane website. PMID- 29796094 TI - Point prevalence survey of indwelling urinary catheter use and appropriateness in patients living at home and receiving a community nursing service in Ireland. AB - Background: Indwelling urinary catheters (IUC) are reported as the most common indwelling device in hospitals and residential/care home settings. Aim: The aim of this study was to assess the prevalence and appropriateness of IUCs in people living at home and receiving a community nursing service. Methods: An IUC self report questionnaire was sent to 66 community nurses in one community care area. A second questionnaire was completed by the researcher on each patient (n = 80) identified by the community nurses. Data were analysed using descriptive statistics and the chi-square test was used to test associations between patient demographics, catheter changes and nurses documentation. Results: The self-report questionnaire was completed by 46 of the 52 areas (88% response rate). The overall prevalence of IUCs was 1.9% with a higher prevalence among men (70%) and in the over-85-years age group (31%). The mean age was 76 years (age range = 34 98 years) and duration of use was approximately four years. Routine IUC changes were carried out by community nurses (52%), in the acute hospital (25%) or by general practitioners (20%) and the type of catheter influenced person/location of catheter changes (P = 0.001). Discussion: This study adds to the understanding of IUCs in patients at home and is the first to investigate if the IUC is appropriate in this setting. It prompted a review of current guidance and development of standard documentation for IUC management locally to ensure that the IUC in use is appropriate. It also suggests that there is a need for internationally accepted, appropriate indications for long-term IUC use to facilitate consistency and allow comparison across studies in future. PMID- 29796095 TI - Infection prevention and control: Who is the judge, you or the guidelines? AB - Objectives: The aim of this study was to explore the attitudes and behaviours of registered nurses and their colleagues around the adoption of standard precautions in order to determine strategies to promote adherence. Design: A qualitative exploratory descriptive design used interviews and focus group to collect data. Setting: Registered nurses and registered midwifes from a tertiary metropolitan hospital took part in the study. Participants: A voluntary sample of 29 adults was recruited from the Australian nursing (n = 25) and midwifery (n = 4) workforce. There were six men (mean age = 36.83 years; SD = 8.93) and 23 women (mean age = 41.36 years; SD = 10.25). Participants were recruited through advertisement on notice boards and emails from unit managers. Results: Thematic analysis revealed five themes but the focus here is on staff judgements which are against the guidelines. Participants indicated that where in their judgement the patient posed no risk and they judged themselves skilled in the procedure, they were justified in deviating from the guidelines. Some staff judgements appeared to be self-protecting, while others were irrational and inconsistent. Conclusions: Despite use of standard precautions being mandated, staff often deviated from them based on their own assessment of the situation or the patient. Any deviance from the guidelines is of concern but especially so when staff take it upon themselves to apply their own criteria or judgements. These results also suggest there may be some organisational inadequacies with regards to training and supervision of staff. PMID- 29796096 TI - Impact of Clostridium difficile toxin gene PCR result on decisions to de-isolate patients: Do the ends justify the means? AB - We aimed to determine how often Clostridium difficile toxin gene PCR assay (CDPCR)-negative patients were appropriately removed from single room contact isolation. Hospital databases were used to collect information on glutamate dehydrogenase (GDH)-positive, toxin-negative inpatients (February-April 2015). Of 60 CDPCR-negative patients, only two (3%) were removed from single room isolation. At least 36% of 53 CDPCR-positive results did not influence bed management. In conclusion, identification of C. difficile toxigenic status did not impact significantly on decisions whether to continue single room isolation. Cost-benefit analysis should be undertaken before CDPCR testing is introduced. PMID- 29796093 TI - Hand hygiene compliance monitoring in anaesthetics: Feasibility and validity. AB - Background: Hand hygiene compliance scores in the anaesthetic department of an acute NHS hospital were persistently low. Aims: To determine the feasibility and validity of regular accurate measurement of HHC in anaesthetics and understand the context of care delivery, barriers and opportunities to improve compliance. Methods: The hand hygiene compliance of one anaesthetist was observed and noted by a senior infection control practitioner (ICP). This was compared to the World Health Organization five moments of hand hygiene and the organisation hand hygiene tool. Findings: In one sequence of 55 min, there were approximately 58 hand hygiene opportunities. The hand hygiene compliance rate was 16%. The frequency and speed of actions in certain periods of care delivery made compliance measurement difficult and potentially unreliable. During several activities, taking time to apply alcohol gel or wash hands would have put the patients at significant risk. Discussion: We concluded that hand hygiene compliance monitoring by direct observation was invalid and unreliable in this specialty. It is important that hand hygiene compliance is optimal in anaesthetics particularly before patient contact. Interventions which reduce environmental and patient contamination, such as cleaning the patient and environment, could ensure anaesthetists encounter fewer micro-organisms in this specialty. PMID- 29796097 TI - Recipes for simulated vomitus. AB - We developed and demonstrated the stability of recipes for simulated vomitus for use in experiments characterizing occupational exposures to body fluid during simulated healthcare activities. The recipes can be easily adapted to make other simulated bodily fluids at low costs and surrogates added to facilitate detection. PMID- 29796098 TI - Outbreak column 21: Tuberculosis (TB): Still a nosocomial threat. AB - This outbreak column explores the epidemiology and infection prevention guidance on tuberculosis (TB) in the UK. The column finds that, at present, national guidance leaves UK hospitals ill-prepared to prevent nosocomial TB transmission. Reasons for this conclusion are as follows: (1) while TB is predominantly a disease that affects people with 'social ills', it has the potential to infect anyone who is sufficiently exposed; (2) nosocomial transmission is documented throughout history; (3) future nosocomial exposures may involve less treatable disease; and (4) current UK guidance is insufficient to prevent nosocomial transmission and is less than that advocated by the World Health Organization and the Centers for Disease Control and Prevention. PMID- 29796100 TI - Diary. PMID- 29796099 TI - Screening and diagnosis of Zika in the Emergency Department. PMID- 29796101 TI - Introduction to the BESS/BOA PJI guidelines. PMID- 29796102 TI - Investigation and Management of Periprosthetic Joint Infection in the Shoulder and Elbow: Evidence and consensus based guidelines of the British Elbow and Shoulder Society. PMID- 29796103 TI - Does structural integrity following rotator cuff repair affect functional outcomes and pain scores? A meta-analysis. AB - Background: To assess whether the integrity of rotator cuff repairs has an impact on functional outcomes, as well as pain scores, after surgery. Methods: Systematic review and meta-analyses performed for Level Iota, IotaIota and IotaIotaIota studies that presented functional outcome scores and radiological assessment of integrity following rotator cuff repair. Extracted data included patient demographics, functional outcome scores [Constant Score, University of California at Los Angeles (UCLA) shoulder score, American Shoulder and Elbow Surgeons (ASES) shoulder score, visual analogue scale (VAS) Pain score], as well as assessment of repair integrity on radiological investigations. A meta-analysis was performed using weighted means and a random effects model. Results: Twelve studies were included in the final analysis. Average re-tear rate for the 800 included patients was 22% at a mean follow-up of 27.5 months after surgery. Patients with intact repairs had a significantly higher Constant Score (8.61 points, p < 0.00001), UCLA shoulder score (2.96 points, p < 0.0001) and ASES shoulder score (9.49 points, p < 0.0006). Patients with intact repairs also reported lower pain VAS Pain scores by 0.62 points (p < 0.0004). Conclusions: Our results show better functional outcome and pain scores in patients with intact rotator cuffs at follow-up when compared to those that have re-torn. This difference is equivalent to the published Minimal Clinically Important Difference for the ASES but not Constant Scores. This review has also highlighted that shoulder strength in patients with intact cuff repairs is likely to be greater than in patients with a failed repair. PMID- 29796104 TI - Ultrasound-guided injections for supraspinatus tendinopathy: corticosteroid versus glucose prolotherapy - a randomized controlled clinical trial. AB - Background: Subacromial corticosteroid injections are frequently performed for pain associated with supraspinatus tendinopathy. Glucose prolotherapy has been used clinically for multiple tendinopathies and is hypothesized to be an alternate injection therapy for supraspinatus tendinopathy. Methods: A prospective, randomized, double blinded clinical trial was conducted. Thirty-six patients with supraspinatus tendinopathy were randomized into two groups: 17 received an ultrasound-guided injection of glucose into the tendinopathic parts of the supraspinatus tendon and 19 received an ultrasound-guided injection of corticosteroid into the subacromial bursa. Primary outcome was level of pain with overhead activities at 3 months. Secondary outcome measures included level and frequency of pain and function, shoulder range of motion, impingement tests, strength and tendon changes on ultrasound. Results: Level of pain with overhead activities was significantly reduced at the 3-month follow-up in the prolotherapy group and at the 6-month follow-up for both the prolotherapy and corticosteroid groups. There were no significant differences between the groups at any time point. Conclusions: Both glucose prolotherapy and corticosteroid were generally well tolerated; however, glucose prolotherapy offered no additional benefit over subacromial corticosteroid injection for supraspinatus tendinopathy. PMID- 29796105 TI - The incidence and causative organisms of infection in elective shoulder surgery. AB - Background: Deep infection remains a serious complication of orthopaedic surgery. Knowledge of infection rates and causative organisms is important to guide infection control measures. The aim of the present study was to determine infection rates and causative organisms in elective shoulder surgery. Methods: Cases complicated by infection were identified and prospectively recorded over a 2-year period. All patients undergoing elective shoulder surgery in the concurrent period at a single Specialist Upper Limb Unit in the UK were identified from the hospital electronic database. Results: In total, 1574 elective shoulder cases were performed: 1359 arthroscopic (540 with implant insertion) and 215 open (197 with implant insertion). The overall infection rate in open surgery of 2.5% was significantly higher than arthroscopic implant cases at 0.7% (p < 0.005). The overall infection rate in implant arthroscopic surgery was significantly higher at 0.7% compared to 0% in non-implant related surgery. (p < 0.05). Conclusions: Patients undergoing open shoulder surgery have a significantly higher risk of infection compared to arthroscopic shoulder surgery. Arthroscopic surgery with implant insertion has a statistically significantly higher risk of developing deep infection compared to procedures with no implant insertion. We recommend prophylactic antibiotics in open shoulder surgery and arthroscopic shoulder surgery with implant insertion. PMID- 29796106 TI - Simulation of bone-determined range of motion in proximal humeral fractures. AB - Background: Predicting the outcome following fractures of the proximal humerus is an important consideration when effectively counselling patients and planning treatment. The purpose of the present study was to analyze different proximal humeral fracture configurations, using a computerized simulation model, aiming to predict the range of motion (ROM). Methods: The computer tomography scans of 79 proximal humeral fractures were analyzed using a customized software system that simulated the range of movement at the glenohumeral joint. Four fracture patterns were investigated: (1) head split fractures; (2) greater tuberosity fractures; (3) lesser tuberosity fractures; and (4) combined tuberosity fractures. Results: Intra-articular fractures had the smallest mean (SE) range of abduction and forward flexion [34.3 degrees (6.6 degrees ) and 60.7 degrees (12.4 degrees )]. Isolated displaced greater tuberosity resulted in limited abduction but not forward flexion [75.0 degrees (5.9 degrees ) and 118.2 degrees (4.9 degrees )]. Isolated lesser tuberosity fractures displayed a ROM comparable to that of healthy subjects [89.3 degrees (3.3 degrees ) and 122.6 degrees (3.4 degrees ) versus 102.3 degrees (2.8 degrees ) and 96.2 degrees (3.8 degrees )]. The reduced head inclination angle was a relatively strong predictor of a limited range of abduction for all fracture types. Conclusions: The present study describes a novel simulation system used to quantify the bone-determined ROM in proximal humeral fractures and may be a useful adjunct in the diagnostic armamentarium for proximal humeral fractures. PMID- 29796107 TI - A 3D comparison of humeral head retroversion by sex and measurement technique. AB - Background: Accurate humeral head reconstruction during shoulder arthroplasty is partially dependent on correctly estimating and replicating native version. The present study evaluated the effects of sex and measurement technique on three dimensional (3D) humeral version measurements made using the transepicondylar, forearm and flexion-extension axes. Methods: Fifty-two full-arm computed tomography scans were converted to 3D models and geometry extracted to define landmarks and coordinate systems. An anatomic humeral head osteotomy plane was used to measure version relative to the three measurement techniques and compare between sexes. Results: The measurement technique used had a significant affect (p < 0.001) on the resulting version measurement. The forearm axis technique consistently resulted in higher measured version compared to either the flexion extension [mean (SD) males 9 degrees (4 degrees ), females 13 degrees (5 degrees ), p < 0.001] or the transepicondylar axes [mean (SD) males 8 degrees (4 degrees ), females 11 degrees (4 degrees ), p < 0.001]. Version in males was 7 degrees greater than females when referencing either the flexion-extension [p = 0.029; mean (SD) males 37.7 degrees (11 degrees ), females 30.4 degrees (13 degrees )] or transepicondylar axes [p = 0.045; mean (SD) males 39 degrees (11 degrees ), females 32 degrees (12 degrees )]. Conclusions: The choice of measurement technique can affect the humeral version angle. These results are important because measuring version using the epicondyles pre-operatively, and subsequently the forearm intra-operatively, will result in approximately 10 degrees under-retroverted osteotomy. For example, 0 degrees neutral version cut during reverse arthroplasty measured referencing the forearm results in 10 degrees anteverted osteotomy when referencing the distal humerus. PMID- 29796108 TI - Arthroscopic repair of bony Bankart lesions in collision athletes. AB - Background: The present study aimed to report the outcomes of acute and subacute arthroscopic bony Bankart repairs in collision athletes. Methods: We reviewed 22 consecutive rugby players with traumatic anterior glenohumeral instability who underwent arthroscopic bony Bankart repair within 4 months of injury over a 2 year period. All lesions were less than 25% of the glenoid bony area. Results: A significant improvement was noted at three months and was maintained at 28 months postoperatively. The mean Constant score improved from 61.5 to 84.1, the mean Oxford shoulder score decreased from 26.3 to 13.6 and the mean Oxford instability score decreased from 42.9 to 13.5. The mean satisfaction score was 8.3 out of 10 at final follow-up. All patients returned to their pre-injury sporting level. Twenty patients (91%) remained stable and asymptomatic, although two (9%) had recurrent instability after further traumatic sports injuries. One required a modified Latarjet procedure, whereas the other patient sustained a soft tissue Bankart lesion and had a revision arthroscopic repair. Conclusions: Acute and sub acute bony Bankart lesions in collision athletes can be addressed through arthroscopic repair with a satisfactory outcome and return to pre-injury level of sport. PMID- 29796110 TI - Outcomes following surgical management of complex terrible triad injuries of the elbow: a single surgeon case series. AB - Background: Terrible triad injuries of the elbow are complex injuries to treat and we report our outcomes following surgical management. Methods: Twenty-two consecutive patients who underwent fixation of terrible triad injuries between 2007 and 2012 were identified. Clinical outcomes were assessed by examination, visual analogue scores (VAS), Oxford Elbow Score (OES), Mayo Elbow Performance Index (MEPI) and QuickDash score (QD). Results: The mean age of patients was 47 years, with a mean follow-up of 32 months. All patients underwent lateral ligament repair, with additional medial ligament repair in four cases. Thirteen patients required repair of the coronoid and 18 patients required surgery to the radial head. The mean flexion-extension arc was 113 degrees , with mean prono supination of 136 degrees . The functional elbow scores revealed good outcomes in the majority (mean OES of 37, MEPI of 79 and QD of 21). The overall complication rate was 41%. In total, 23% required reoperation, with one patient requiring fasciotomy for acute compartment syndrome and four requiring subsequent removal of metalwork as a result of stiffness. Conclusions: Recognition of this complex injury pattern and appropriate restoration of the joint stability are the prerequisites. Systematic surgical approach is effective and can provide both stability and good function, in most cases. PMID- 29796109 TI - Normative values of isometric elbow strength in healthy adults: a systematic review. AB - Background: Post-traumatic deformities such as biceps tendon rupture or (peri )articular fractures of the elbow are often related to a decrease in muscle strength. Postoperative evaluation of these deformities requires normative values of elbow strength. The purpose of this systematic review was to determine these normative values of isometric elbow strength in healthy adults resulting from studies evaluating this strength (i.e. flexion, extension, pronation and supination strength). Methods: The databases of PubMed, EMBASE and Web of Sciences were searched and screened for studies involving the isometric elbow strength as measured in asymptomatic volunteers. The quality of the studies was assessed and studies of low quality were excluded. Results: Nineteen studies met the inclusion criteria and were of sufficiently high quality to be included in the present review. In these studies, elbow strength was measured in a total of 1880 healthy volunteers. The experimental set-up and devices used to measure elbow strength varied between studies. Using some assumptions, a normative values table was assembled. Conclusions: Large standard deviations of normative values in combination with different measurement devices used, as well as the different measurement positions of the subjects, demonstrated that there is no consensus about measuring the isometric elbow strength and therefore the normative values have to be interpreted with caution. PMID- 29796111 TI - Arthroscopic debridement for primary elbow osteoarthritis with and without capsulectomy: a comparative cohort study. AB - Background: Arthroscopic elbow debridement for primary osteoarthritis may be performed with or without a joint capsulectomy. The purpose of this comparative cohort study was to compare range of motion (ROM) and early complications between patients with and without anterior capsulectomy. Methods: In total, 110 patients with primary osteoarthritis of the elbow who underwent an arthroscopic debridement for primary osteoarthritis were reviewed with a minimum of 3 months postoperative follow-up. The first group consisted of 51 patients who had a concomitant capsulectomy and the second group consisted of 59 patients who either had a capsulotomy or did not have the capsule addressed. Results: There was significantly greater pre-operative stiffness in the group who had an anterior capsulectomy versus those who did not. A greater improvement in arc of ROM occurred in patients who had a concomitant capsulectomy compared to patients without (24 degrees versus 12 degrees ) (p < 0.003); however, there were no significant differences in final ROM between groups. There were no statistically significant differences in the incidence of complications between the groups (16% capsulectomy versus 18% no capsulectomy). Conclusions: Elbow arthroscopy and debridement for primary elbow osteoarthritis yields satisfactory motion at short term follow-up with or without a capsulectomy. The incidence of early complications was low at this tertiary referral centre, with no significant differences between groups. PMID- 29796112 TI - Assessing the added predictive ability of a metabolic syndrome severity score in predicting incident cardiovascular disease and type 2 diabetes: the Atherosclerosis Risk in Communities Study and Jackson Heart Study. AB - Background: The severity of the metabolic syndrome (MetS) predicts future coronary heart disease (CHD) and diabetes independent of the individual MetS components. Our aim was to evaluate whether MetS severity conferred additional discrimination to existing scoring systems for cardiovascular disease (CVD) and diabetes risk. Methods: We assessed Cox proportional hazard models of CHD- and diabetes risk among 13,141 participants of the Atherosclerosis Risk in Communities Study and the Jackson Heart Study, using the Framingham Risk Calculator, the American Heart Association's Atherosclerotic CVD calculator, the American Diabetes Association diabetes risk score and an additional diabetes risk score derived from ARIC data. We then added a MetS-severity Z-score to these models and assessed for added risk discrimination by assessing Akaike information criterion, c-statistic, integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI). Results: The MetS severity score appears to add to the predictive ability of individual CHD and diabetes risk scores. Using the IDI, MetS improved risk prediction for diabetes but not CHD risk. In all 4 scoring systems, MetS severity had a significant non-event NRI, improving the ability to exclude individuals without events. Assessing interactions between risk scores and MetS severity revealed that MetS severity was more highly associated with disease risk among those in the lowest quintiles of risk score, suggesting that MetS was particularly able to identify risk among individuals judged to be of low risk by existing algorithms. Conclusions: Mets severity improved prediction of diabetes more so than CHD. Incorporation of multiple risk predictors into electronic health records may help in better identifying those at high disease risk, who can then be placed earlier on preventative therapy. PMID- 29796113 TI - Dietary and genetic risk scores and incidence of type 2 diabetes. AB - Background: Both lifestyle and genetic predisposition determine the development of type 2 diabetes (T2D), and studies have indicated interactions between specific dietary components and individual genetic variants. However, it is unclear whether the importance of overall dietary habits, including T2D-related food intakes, differs depending on genetic predisposition to T2D. We examined interaction between a genetic risk score for T2D, constructed from 48 single nucleotide polymorphisms identified in genome-wide association studies, and a diet risk score of four foods consistently associated with T2D in epidemiological studies (processed meat, sugar-sweetened beverages, whole grain and coffee). In total, 25,069 individuals aged 45-74 years with genotype information and without prevalent diabetes from the Malmo Diet and Cancer cohort (1991-1996) were included. Diet data were collected with a modified diet history method. Results: During 17-year follow-up, 3588 incident T2D cases were identified. Both the diet risk score (HR in the highest risk category 1.40; 95% CI 1.26, 1.58; P trend = 6 * 10-10) and the genetic risk score (HR in the highest tertile of the genetic risk score 1.67; 95% CI 1.54, 1.81; P trend = 7 * 10-35) were associated with increased incidence of T2D. No significant interaction between the genetic risk score and the diet risk score (P = 0.83) or its food components was observed. The highest risk was seen among the 6% of the individuals with both high genetic and dietary risk scores (HR 2.49; 95% CI 2.06, 3.01). Conclusions: The findings thus show that both genetic heredity and dietary habits previously associated with T2D add to the risk of T2D, but they seem to act in an independent fashion, with the consequence that all individuals, whether at high or low genetic risk, would benefit from favourable food choices. PMID- 29796114 TI - Circulating tumour DNA for monitoring colorectal cancer-a prospective cohort study to assess relationship to tissue methylation, cancer characteristics and surgical resection. AB - Background: Cell-free circulating tumour-derived DNA (ctDNA) can be detected by testing for methylated BCAT1 and IKZF1 DNA, which has proven sensitivity for colorectal cancer (CRC). A prospective correlative biomarker study between presence of methylated BCAT1 and IKZF1 in tissue and blood was conducted in cases with CRC to explore how detection of such ctDNA biomarkers relates to cancer characteristics, methylation in tissue and surgical resection of the primary cancer. Methods: Enrolled patients with invasive CRC had blood collected at diagnosis, prior to any treatment or surgery (peri-diagnostic sample). A subgroup of patients also had cancer and adjacent non-neoplastic tissue collected at surgical resection, as well as a second blood sample collected within 12 months of surgery (post-surgery sample). DNA was extracted from all samples and assayed for methylated BCAT1 and IKZF1 to determine the degree of methylation in tissue and the presence of ctDNA in blood. Results: Of 187 cases providing peri diagnostic blood samples, tissue was available in 91, and 93 provided at least one post-surgery blood sample for marker analysis. Significant methylation of either BCAT1 or IKZF1 was seen in 86/91 (94.5%) cancer tissues, with levels independent of stage and higher than that observed in adjacent non-neoplastic specimens (P < 0.001). ctDNA methylated in BCAT1 or IKZF1 was detected in 116 (62.0%) cases at diagnosis and was significantly more likely to be detected with later stage (P < 0.001) and distal tumour location (P = 0.004). Of the 91 patients who provided pre-and post-surgery blood samples, 47 patients were ctDNA positive at diagnosis and 35 (74.5%) became negative after tumour resection. Conclusion: This study has shown that BCAT1 and IKZF1 methylation are common events in CRC with almost all cancer tissues showing significant levels of methylation in the two genes. The presence of ctDNA in blood is stage-related and show rapid reversion to negative following surgical resection. Monitoring methylated BCAT1 and IKZF1 levels could therefore inform adequacy of surgical resection. Trial registration: Australian New Zealand Clinical Trial Registry number 12611000318987. Registered 25 March 2011. PMID- 29796115 TI - miR-29c plays a suppressive role in breast cancer by targeting the TIMP3/STAT1/FOXO1 pathway. AB - Background: miR-29c has been associated with the progression of many cancers. However, the function and mechanism of miR-29c have not been well investigated in breast cancers. Methods: Real-time quantitative PCR was used to assess expression of miR-29c and DNMT3B mRNA. Western blot and immunochemistry were used to examine the expression of DNA methyltransferase 3B (DNMT3B) protein in breast cancer cells and tissues. The functional roles of miR-29c in breast cancer cells such as proliferation, migration, invasion, colony formation, and 3D growth were evaluated using MTT, transwell chambers, soft agar, and 3D Matrigel culture, respectively. In addition, the luciferase reporter assay was used to check if miR 29c binds the 3'UTR of DNMT3B. The effects of miR-29c on the DNMT3B/TIMP3/STAT1/FOXO1 pathway were also examined using Western blot and methyl specific qPCR. The specific inhibitor of STAT1, fludarabine, was used to further check the mechanism of miR-29c function in breast cancer cells. Studies on cell functions were carried out in DNMT3B siRNA cell lines. Results: The expression of miR-29c was decreased with the progression of breast cancers and was closely associated with an overall survival rate of patients. Overexpression of miR-29c inhibited the proliferation, migration, invasion, colony formation, and growth in 3D Matrigel while knockdown of miR-29c promoted these processes in breast cancer cells. In addition, miR-29c was found to bind 3'UTR of DNMT3B and inhibits the expression of DNMT3B, which was elevated in breast cancers. Moreover, the protein level of TIMP3 was reduced whereas methylation of TIMP3 was increased in miR-29c knockdown cells compared to control. On the contrary, the protein level of TIMP3 was increased whereas methylation of TIMP3 was reduced in miR-29c-overexpressing cells compared to control. Knockdown of DNMT3B reduced the proliferation, migration, and invasion of breast cancer cell lines. Finally, our results showed that miR-29c exerted its function in breast cancers by regulating the TIMP3/STAT1/FOXO1 pathway. Conclusion: The results suggest that miR-29c plays a significant role in suppressing the progression of breast cancers and that miR 29c may be used as a biomarker of breast cancers. PMID- 29796116 TI - Genome-wide analysis of DNA methylation in bronchial washings. AB - Background: The objective of this study was to discover DNA methylation biomarkers for detecting non-small lung cancer (NSCLC) in bronchial washings and understanding the association between DNA methylation and smoking cessation. Methods: DNA methylation was analyzed in bronchial washing samples from 70 NSCLCs and 53 hospital-based controls using Illumina HumanMethylation450K BeadChip. Methylation levels in these bronchial washings were compared to those in 897 primary lung tissues of The Cancer Genome Atlas (TCGA) data. Results: Twenty-four CpGs (p < 1.03E-07) were significantly methylated in bronchial washings from 70 NSCLC patients compared to those from 53 controls. The CpGs also had significant methylation in the TCGA cohort. The 123 participants were divided into a training set (N = 82) and a test set (N = 41) to build a classification model. Logistic regression model showed the best performance for classification of lung cancer in bronchial washing samples: the sensitivity and specificity of a marker panel consisting of seven CpGs in TFAP2A, TBX15, PHF11, TOX2, PRR15, PDGFRA, and HOXA11 genes were 87.0 and 83.3% in the test set, respectively. The area under the curve (AUC) was equal to 0.87 (95% confidence interval = 0.73-0.96, p < 0.001). Methylation levels of two CpGs in RUNX3 and MIR196A1 genes were inversely associated with duration of smoking cessation in the controls, but not in NSCLCs, after adjusting for pack-years of smoking. Conclusions: The present study suggests that NSCLC may be detected by analyzing methylation changes of seven CpGs in bronchial washings. Furthermore, smoking cessation may lead to decreased DNA methylation in nonmalignant bronchial epithelial cells in a gene-specific manner. PMID- 29796117 TI - Postnatal relative adrenal insufficiency results in methylation of the glucocorticoid receptor gene in preterm infants: a retrospective cohort study. AB - Background: To investigate the relationship between early-life stress and glucocorticoid receptor (GR) gene methylation, which may result in long-lasting neurodevelopmental impairment, we performed a longitudinal analysis of the methylation ratio within the GR gene promoter 1F region using next-generation sequencing in preterm infants.Cell-free DNA was extracted from the frozen serum of 19 preterm birth infants at birth and at 1 and 2 months after birth. All were admitted to the neonatal intensive care unit of Juntendo University Shizuoka Hospital between August 2014 and May 2016 and suffered from chronic lung disease (CLD).Through bisulfite amplicon sequencing using an Illumina Miseq system and Bismark-0.15.0 software, we identified the rate of cytosine methylation. Results: Patients' sex and body weight standard deviation were extracted as the associated independent variables at birth. Sex, glucocorticoid administration for treating CLD, and postnatal invasive procedures (surgical operation and blood sampling) were extracted as the associated independent variables at 1 month. Methylation rates increased significantly between postnatal 1 and 2 months at 9 of the 39 CpG sites. Postnatal glucocorticoid administration to treat circulatory collapse was the most-associated independent variable with a positive regression coefficient for a change in methylation rate at these nine CpG sites. It also influenced the methylation ratio at 22 of the 39 CpG sites at 2 months of age. The standard deviation (SD) score at birth was extracted as an independent variable, with a negative regression coefficient at 9 of the 22 CpG sites together with glucocorticoid administration. Conclusions: The results of this study indicate that a prenatal environment that results in intrauterine growth restriction and postnatal relative adrenal insufficiency requiring glucocorticoid administration leads to GR gene methylation. That, in turn, may result in neurodevelopmental disabilities. PMID- 29796118 TI - Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice. AB - Background: Transplantation of human hematopoietic stem cells into immunodeficient mice provides a powerful in vivo model system to gain functional insights into hematopoietic differentiation. So far, it remains unclear if epigenetic changes of normal human hematopoiesis are recapitulated upon engraftment into such "humanized mice." Mice have a much shorter life expectancy than men, and therefore, we hypothesized that the xenogeneic environment might greatly accelerate the epigenetic clock. Results: We demonstrate that genome-wide DNA methylation patterns of normal human hematopoietic development are indeed recapitulated upon engraftment in mice-particularly those of normal early B cell progenitor cells. Furthermore, we tested three epigenetic aging signatures, and none of them indicated that the murine environment accelerated age-associated DNA methylation changes. Conclusions: Epigenetic changes of human hematopoietic development are recapitulated in the murine transplantation model, whereas epigenetic aging is not accelerated by the faster aging environment and seems to occur in the cell intrinsically. PMID- 29796121 TI - Pharmacists as cognitive authorities: Why this is important in advancing patient care and our profession. PMID- 29796119 TI - An epigenetic classifier for early stage lung cancer. AB - Background: Methylated genes detected in sputum are promise biomarkers for lung cancer. Yet the current PCR technologies for quantification of DNA methylation and diagnostic value of the sputum biomarkers are not sufficient to be used for lung cancer early detection. The emerging droplet digital PCR (ddPCR) is a straightforward means for precise, direct, and absolute quantification of nucleic acids. Here, we investigate whether ddPCR can sensitively and robustly quantify DNA methylation in sputum for more precise diagnosis of lung cancer. Results: First, the analytic performance of methylation-specific ddPCR (ddMSP) and quantitative methylation-specific PCR (qMSP) is determined in methylated and unmethylated DNA samples. Second, 29 genes, previously proposed as potential sputum biomarkers for lung cancer, are analyzed by using ddMSP in a training set of 127 lung cancer patients and 159 controls. ddMSP has higher sensitivity, precision, and reproducibility for quantification of methylation compared with qMSP (all p < 0.05). A classifier comprising four sputum methylation biomarkers for lung cancer is developed by using ddMSP, producing 86.6% sensitivity and 90.6% specificity, independent of stage and histology of lung cancer (all p > 0.05). The classifier has higher accuracy compared with sputum cytology (88.8 vs. 70.6%, p < 0.01). The diagnostic performance is confirmed in a testing set of 89 cases and 107 controls. Conclusions: ddMSP is a robust tool for reliable quantification of DNA methylation in sputum, and the epigenetic classifier could help diagnose lung cancer at the early stage. PMID- 29796120 TI - Retinoic acid-induced 2 (RAI2) is a novel tumor suppressor, and promoter region methylation of RAI2 is a poor prognostic marker in colorectal cancer. AB - Background: Reduced expression of retinoic acid-induced 2 (RAI2) was found in breast cancer. The regulation and function of RAI2 in human colorectal cancer (CRC) remain unclear. Methods: Eight CRC cell lines and 237 cases of primary CRC were analyzed. Methylation-specific PCR (MSP), flow cytometry, xenograft mouse model, and shRNA technique were employed. Results: RAI2 was completely methylated in RKO, LOVO, and HCT116 cells; partially methylated in HT29 cells; and unmethylated in SW480, SW620, DLD1, and DKO cells. RAI2 was methylated in 53.6% (127/237) of primary colorectal cancer. Methylation of RAI2 was significantly associated with gender (P < 0.001), TNM stage (P < 0.001), and lymph node metastasis (P < 0.001). Analyzing by the Kaplan-Meier method, methylation of RAI2 was significantly associated with poor 5-year overall survival (OS) (P = 0.0035) and 5-year relapse-free survival (RFS) (P = 0.0062). According to Cox proportional hazards model analysis, RAI2 methylation was an independent poor prognostic marker for 5-year OS (P = 0.002) and poor 5-year RFS (P = 0.022). RAI2 suppressed cell proliferation, migration, and invasion and induced cell apoptosis in CRC. In addition, RAI2 inhibited AKT signaling in CRC cells and suppressed human CRC cell xenograft growth in mice. Conclusion: RAI2 is frequently methylated in human CRC, and the expression of RAI2 is regulated by promoter region methylation. Methylation of RAI2 is an independent poor prognostic marker of CRC. RAI2 suppresses CRC cell growth both in vitro and in vivo. RAI2 suppresses CRC by inhibiting AKT signaling. PMID- 29796122 TI - Shared decision making and high blood pressure. PMID- 29796123 TI - Reply from authors. PMID- 29796124 TI - Cover: July 1909. PMID- 29796125 TI - The pharmaceutical department: August 1917. PMID- 29796126 TI - The pharmacist in the army: July 1918. PMID- 29796127 TI - Women in pharmacy: June 1918. PMID- 29796128 TI - Professional opportunity for pharmacists to integrate pharmacogenomics in medication therapy. PMID- 29796129 TI - Prioritizing intraprofessional collaboration for optimal patient care: A call to action. PMID- 29796130 TI - Top 5 primary care topics for pharmacists in 2016. PMID- 29796133 TI - Uptake and impact of regulated pharmacy technicians in Ontario community pharmacies. AB - Background: Since 2010, most provincial Colleges of Pharmacists have licensed pharmacy technicians. The colleges hoped this would give pharmacists time to provide "expanded scope" activities such as medication reviews. Little is known, however, about the uptake and impact of pharmacy technicians on pharmacists' provision of such services. We address these questions using data for Ontario community pharmacies. Methods: Data on pharmacists and pharmacy technicians were obtained from the Ontario College of Pharmacists website in September 2016. Their place of employment was used to calculate the number of full-time equivalent (FTE) pharmacists and technicians employed at each community pharmacy. Pharmacy claims data for the 12-month period ending March 31, 2016, were obtained from the Ontario Public Drug Programs (OPDP). These data included number of MedsChecks performed, type of MedsCheck and number of prescriptions dispensed to OPDP beneficiaries. Results: Pharmacy technicians were employed in 24% of the pharmacies in our sample. Technician employment rates were highest in Central Fill pharmacies and pharmacies serving long-term care facilities. In general, pharmacies employing 1 or fewer technician full-time equivalents (FTEs) had a slightly higher probability of providing MedsChecks and, of those that did provide Meds Checks Annuals, provided more of them. Pharmacies that hired 3 or more technician FTEs were markedly less likely to provide MedsChecks. Conclusions: Pharmacies differ in their employment of technicians and in the apparent impact of technicians on the provision of MedsChecks. However, these represent associations. Additional research is needed to assess the causal effect of technician employment on the provision of MedsChecks. PMID- 29796132 TI - Facilitating integration of regulated pharmacy technicians into community pharmacy practice in Ontario: Results of an exploratory study. AB - Background: The integration of regulated pharmacy technicians (RPTs) into community pharmacy practice was intended to relieve pharmacists of certain technical duties to facilitate greater provision of direct patient care services, commensurate with expanded scope of practice. There is scant data available regarding the success, value and impact of RPT integration, either in Canada or in other jurisdictions. Methods: Pharmacists and RPTs working in community practices were interviewed. Qualitative data were categorized using an iterative coding process to identify themes related to barriers and facilitators to integrating and optimizing the role of the RPT in community practice in Ontario. Results: A total of 16 RPTs and 12 pharmacists were interviewed from community sites in Ontario. Strategies for facilitating successful integration of RPTs into daily workflow were identified, based on 4 major themes: environmental factors, interpersonal factors, professional identity formation and innovative use of delegation. Interpretation: Integration of RPTs into community practice is complex and requires careful management, planning, training and follow-up to ensure attainment of objectives. Simply hiring RPTs and placing them into existing workflow patterns is generally not a successful implementation strategy. Conclusions: Implementation strategies identified through this study can provide employers, managers, pharmacists and RPTs with opportunities to enhance RPT integration and optimize the role of both pharmacists and RPTs in community practice. PMID- 29796131 TI - Prevention and management of statin adverse effects: A practical approach for pharmacists. AB - Statin-associated adverse effects, primarily muscle-related symptoms, occur in up to approximately one-third of patients in clinical practice. Recently, a Canadian Consensus Working Group outlined 6 key principles to assess and manage patients with goal-inhibiting statin intolerance, defined as a syndrome characterized by symptoms or biomarker abnormalities that prevent the long-term use of and adherence to indicated statin therapy, which includes a trial of at least 2 statins and precludes reversible causes of statin adverse effects. These principles ensure patients are appropriately receiving a statin and aware of both the benefits and risks of therapy. As well, they address factors that may increase the risk of statin-associated myopathy. A thorough assessment of patients' clinical and laboratory history should be performed in any patient presenting with muscle symptoms on statin therapy, followed by a systematic dechallenge/rechallenge approach. In practice, most patients with statin intolerance due to muscle symptoms will be able to tolerate another statin. This is of particular importance because of the relative paucity of compelling evidence demonstrating a cardiovascular benefit with nonstatin therapies. Pharmacists are ideally situated to provide patient education, recommend changes to therapy and monitor patients with goal-inhibiting statin intolerance. PMID- 29796134 TI - Mapping our profession's future. PMID- 29796135 TI - Cross-Canada updates. PMID- 29796136 TI - Canadian Pharmacists Conference 2018. PMID- 29796137 TI - Effects of Habenular Stimulation Frequencies on Obstructive Sleep Apnea Induced by Stimulation of Insular Cortex. AB - Objective: To investigate the effects of high-frequency stimulation of the habenula (Hb) on obstructive sleep apnea (OSA) induced by stimulation of the insular cortex Method. After OSA was induced by stimulating the insular cortex (Ic) with concentric stimulating electrodes at 100 Hz in rats, the Hb was stimulated at different frequencies (50 Hz, 120 Hz, 130 Hz, and 280 Hz). The changes of apnea events and electromyography (EMG) of the genioglossus were compared before and after stimulation of the Hb. Results: With stimulation of the Ic at 100 Hz, apnea events were successfully induced with disappearance of EMG of the genioglossus. After stimulation of the Hb at 130 Hz, apnea events disappeared with significantly increased genioglossal EMG. However, such a change failed to be found at the stimulation frequencies of 50 Hz, 120 Hz, and 280 Hz. Conclusion: Stimulation of the Hb at the frequency of 130 Hz could effectively inhibit OSA events induced by stimulation of the Ic. PMID- 29796138 TI - The Role of Migration in Maintaining the Transmission of Avian Influenza in Waterfowl: A Multisite Multispecies Transmission Model along East Asian Australian Flyway. AB - Background: Migratory waterfowl annually migrate over the continents along the routes known as flyways, serving as carriers of avian influenza virus across distant locations. Prevalence of influenza varies with species, and there are also geographical and temporal variations. However, the role of long-distance migration in multispecies transmission dynamics has yet to be understood. We constructed a mathematical model to capture the global dynamics of avian influenza, identifying species and locations that contribute to sustaining transmission. Methods: We devised a multisite, multispecies SIS (susceptible infectious-susceptible) model, and estimated transmission rates within and between species in each geographical location from prevalence data. Parameters were directly sampled from posterior distribution under Bayesian inference framework. We then analyzed contribution of each species in each location to the global patterns of influenza transmission. Results: Transmission and migration parameters were estimated by Bayesian posterior sampling. The basic reproduction number was estimated at 1.1, slightly above the endemic threshold. Mallard was found to be the most important host with the highest transmission potential, and high- and middle-latitude regions appeared to act as hotspots of influenza transmission. The local reproduction number suggested that the prevalence of avian influenza in the Oceania region is dependent on the inflow of infected birds from other regions. Conclusion: Mallard exhibited the highest transmission rate among the species explored. Migration was suggested to be a key factor of the global prevalence of avian influenza, as transmission is locally sustainable only in the northern hemisphere, and the virus could be extinct in the Oceania region without migration. PMID- 29796139 TI - Pre-recorded instructional audio vs. dispatchers' conversational assistance in telephone cardiopulmonary resuscitation: A randomized controlled simulation study. AB - BACKGROUND: To assess the effectiveness of the telephone chest-compression-only cardiopulmonary resuscitation (CPR) guided by a pre-recorded instructional audio when compared with dispatcher-assisted resuscitation. METHODS: It was a prospective, blind, randomised controlled study involving 109 medical students without previous CPR training. In a standardized mannequin scenario, after the step of dispatcher-assisted cardiac arrest recognition, the participants performed compression-only resuscitation guided over the telephone by either: (1) the pre-recorded instructional audio (n=57); or (2) verbal dispatcher assistance (n=52). The simulation video records were reviewed to assess the CPR performance using a 13-item checklist. The interval from call reception to the first compression, total number and rate of compressions, total number and duration of pauses after the first compression were also recorded. RESULTS: There were no significant differences between the recording-assisted and dispatcher-assisted groups based on the overall performance score (5.6+/-2.2 vs. 5.1+/-1.9, P>0.05) or individual criteria of the CPR performance checklist. The recording-assisted group demonstrated significantly shorter time interval from call receipt to the first compression (86.0+/-14.3 vs. 91.2+/-14.2 s, P<0.05), higher compression rate (94.9+/-26.4 vs. 89.1+/-32.8 min-1) and number of compressions provided (170.2+/-48.0 vs. 156.2+/-60.7). CONCLUSION: When provided by untrained persons in the simulated settings, the compression-only resuscitation guided by the pre recorded instructional audio is no less efficient than dispatcher-assisted CPR. Future studies are warranted to further assess feasibility of using instructional audio aid as a potential alternative to dispatcher assistance. PMID- 29796140 TI - The effect of wilderness and medical training on injury and altitude preparedness among backcountry hikers in Rocky Mountain National Park. AB - BACKGROUND: The purpose of this study was to document the correlation between medical and wilderness training with levels of preparedness for acute mountain sickness (AMS), illness, and injury among backcountry hikers. METHODS: We conducted a cross-sectional, convenience survey in Rocky Mountain National Park in July and August 2015. The study group consisted of 380 hikers who completed a written survey that collected information about demographics, wilderness experience, altitude experience, hiking equipment, communications devices, and trip planning. RESULTS: Factors such as wilderness training (wilderness first aid [WFA], wilderness first responder [WFR], or wilderness emergency medical technician [WEMT]), wilderness experience, and altitude experience all affected hikers' emergency preparedness. Respondents with medical training were more prepared to avoid or respond to AMS (62.3% vs. 34.3% [P<0.001]). They were also more prepared to avoid or manage injury/illness than hikers without medical training (37.7% vs. 20.7% [P=0.003]). Participants with wilderness training were more likely to be prepared to avoid or respond to AMS (52.3% vs. 36.8% [P=0.025]) but not significantly more likely to be prepared to manage illness/injury (31.8% vs. 22.0% [P<0.11]). Adjusting for experience, wilderness training, age, and gender, we found that medical training was associated with increased preparedness for AMS (OR 2.72; 95% CI 1.51-4.91) and injury/illness (OR 2.71; 95% CI 1.5 4.89). CONCLUSION: Medically trained hikers were more likely to be prepared to avoid or manage AMS, medical emergencies, and injuries than their non-medically trained counterparts. Wilderness training increased hikers' preparedness for AMS but did not significantly alter preparedness for illness/injury. PMID- 29796142 TI - Emergency medicine residencies structure of trainees' administrative experience: A cross-sectional survey. AB - BACKGROUND: While the Accreditation Council for Graduate Medical Education (ACGME) mandates that emergency medicine residencies provide an educational curriculum that includes administrative seminars and morbidity and mortality conference, there is significant variation as to how administrative topics are implemented into training programs. We seek to determine the prevalence of dedicated administrative rotations and details about the components of the curriculum. METHODS: In this descriptive study, a 12-question survey was distributed via the CORD listserv; each member program was asked questions concerning the presence of an administrative rotation and details about its components. These responses were then analyzed with simple descriptive statistics. RESULTS: A total of 114 of the 168 programs responded, leading to a 68% response rate. Of responders, 73% have a dedicated administrative rotation (95% CI 64.0 to 80.4). The content areas covered by the majority of programs with a dedicated program include performance improvement (n=68), patient safety (n=64), ED operations (n=58), patient satisfaction (n=54), billing and coding (n=47), and inter-professional collaboration (n=43). Experiential learning activities include review of patient safety reports (n=66) and addressing patient complaints (n=45). Most of the teaching on the rotation is either in-person (n=65) and/or self-directed reading assignments (n=48). The most commonly attended meetings during the rotation include performance improvement (n=60), ED operations (n=59), and ED faculty (n=44). CONCLUSION: This paper provides an overview of the most commonly covered resident administrative experiences that can be a guide as we work to develop an ideal administrative curriculum for EM residents. PMID- 29796141 TI - Prevalence and associated factors of stress, anxiety and depression among emergency medical officers in Malaysian hospitals. AB - BACKGROUND: Demanding profession has been associated with poor psychological health due to multiple factors such as overworking hours and night shifts. This study is to determine prevalence and associated factors of depression, anxiety and stress among medical officers working at emergency department in Malaysian hospitals. METHODS: A cross-sectional study was conducted on 140 emergency department medical officers working at general hospitals from seven Malaysia regions. They were randomly selected and their depression, anxiety and stress level were measured by the 21-item Depression, Anxiety, Stress Scale. RESULTS: The highest prevalence was anxiety (28.6%) followed by depression (10.7%) and stress (7.9%). Depression, anxiety and stress between seven hospitals were not significantly different (P>0.05). Male medical officers significantly experienced more anxiety symptoms than female medical officers (P=0.0022), however depression and stress symptoms between male and female medical officers were not significantly different (P>0.05). Depression, anxiety and stress were not associated with age, working experience, ethnicity, marital status, number of shifts and type of system adopted in different hospitals (P>0.05). CONCLUSION: The prevalence of anxiety was high, whereas for depression and stress were considerably low. Gender was the only factor significantly associated with anxiety. Other factors were not associated with depression, anxiety and stress. Future research should aim to gain better understanding on unique factors that affect female and male medical officers' anxiety level in emergency setting, thus guide authorities to chart strategic plans to remedy this condition. PMID- 29796143 TI - Assessment of toxicology knowledge in the fourth-year medical students: Three years of data. AB - BACKGROUND: Pharmacology and toxicology are core content knowledge for physicians. Medical students should demonstrate understanding of general pharmacology and basic treatment of poisoning. The objective of this study was to measure the knowledge of the 4th-year medical students (MS4) on these topics over 3 years. METHODS: A multiple-choice exam (15 questions) was administered to MS4 students in spring of 2010, 2011, and 2012. Questions were developed by medical toxicologists to evaluate basic knowledge in three areas: pharmacologic effects (PE), treatment of poisoning (TOP), and pharmacokinetics (PK). The students were grouped by intended specialties into pharmacologic intense (anesthesia, emergency medicine, internal medicine, pediatrics, and psychiatry), less pharmacologic intense specialties (dermatology, OB/GYN, ophthalmology, pathology, physical medicine and rehabilitation, radiology, and surgery) and by completion of a pharmacology or toxicology elective. Mean group scores were compared using ANOVA. RESULTS: Totally 332 of 401 (83%) students completed the survey. Mean scores were stable over the three years, higher for students completing a toxicology rotation and for students entering a pharmacologically intense specialty. CONCLUSION: The external validity is limited to a single medical school with incomplete participation and content was limited by the survey length. Consistent results over the three-year period and correlation of performance with completing a toxicology rotation and intent to enter a pharmacology intensive specialty suggest this survey may correlate with toxicology knowledge. Implementation of required core courses focused on toxicology may improve core content knowledge in fourth year medical students. PMID- 29796144 TI - Enoxaparin dosing errors in the emergency department. AB - BACKGROUND: The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department (ED) weight compared to those who did not have a measured ED weight, and to determine if demographic variables (e.g., weight, height, age, English-speaking, race) impact the likelihood of receiving an inappropriate dose. METHODS: This is a retrospective, electronic chart review of patients who received a dose of enoxaparin in the ED between January 1, 2008 and July 1, 2013. We identified all patients >18 years who received a dose of enoxaparin while in the ED, were admitted, and had at least one inpatient weight within the first four days of hospitalization. Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25 mg/kg. RESULTS: A total of 1,944 patients were included. Patients were more likely to experience an error if they did not have a measured ED weight. Over-doses of >10 mg were more likely to occur in patients without a measured ED weight. Patients with no documented ED weight or with a staff estimated ED weight were more likely to experience a dosing error than those with a patient-stated weight. Patients were more likely to experience an error if their first inpatient weight was more than 96 kg, they were more than 175-cm tall, or were English speaking. CONCLUSION: Dosing errors are more likely to occur when patients are not weighed in the ED. Modifications to current workflows to incorporate weighing those patients who receive weight-dosed medications may be warranted. PMID- 29796145 TI - Risk factors for ventilator-associated pneumonia in trauma patients: A descriptive analysis. AB - BACKGROUND: We sought to evaluate the risk factors for developing ventilator associated pneumonia (VAP) and whether the location of intubation posed a risk in trauma patients. METHODS: Data were retrospectively reviewed for adult trauma patients requiring intubation for > 48 hours, admitted between 2010 and 2013. Patients' demographics, clinical presentations and outcomes were compared according to intubation location (prehospital intubation [PHI] vs. trauma room [TRI]) and presence vs. absence of VAP. Multivariate regression analysis was performed to identify predictors of VAP. RESULTS: Of 471 intubated patients, 332 patients met the inclusion criteria (124 had PHI and 208 had TRI) with a mean age of 30.7+/-14.8 years. PHI group had lower GCS (P=0.001), respiratory rate (P=0.001), and higher frequency of head (P=0.02) and chest injuries (P=0.04). The rate of VAP in PHI group was comparable to the TRI group (P=0.60). Patients who developed VAP were 6 years older, had significantly lower GCS and higher ISS, head AIS, and higher rates of polytrauma. The overall mortality was 7.5%, and was not associated with intubation location or pneumonia rates. In the early-VAP group, gram-positive pathogens were more common, while gram-negative microorganisms were more frequently encountered in the late VAP group. Logistic regression analysis and modeling showed that the impact of the location of intubation in predicting the risk of VAP appeared only when chest injury was included in the models. CONCLUSION: In trauma, the risk of developing VAP is multifactorial. However, the location of intubation and presence of chest injury could play an important role. PMID- 29796146 TI - Preventable readmission to intensive care unit in critically ill cancer patients. AB - BACKGROUND: Readmission to intensive care unit (ICU) after discharge to ward has been reported to be associated with increased hospital mortality and longer length of stay (LOS). The objective of this study was to investigate whether ICU readmission are preventable in critically ill cancer patients. METHODS: Data of patients who readmitted to intensive care unit (ICU) at National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) between January 2013 and November 2016 were retrospectively collected and reviewed. RESULTS: A total of 39 patients were included in the final analysis, and the overall readmission rate between 2013 and 2016 was 1.32% (39/2,961). Of 39 patients, 32 (82.1%) patients were judged as unpreventable and 7 (17.9%) patients were preventable. There were no significant differences in duration of mechanical ventilation, ICU LOS, hospital LOS, ICU mortality and in-hospital mortality between patients who were unpreventable and preventable. For 24 early readmission patients, 7 (29.2%) patients were preventable and 17 (70.8%) patients were unpreventable. Patients who were late readmission were all unpreventable. There was a trend that patients who were preventable had longer 1-year survival compared with patients who were unpreventable (100% vs. 66.8%, log rank=1.668, P=0.196). CONCLUSION: Most readmission patients were unpreventable, and all preventable readmissions occurred in early period after discharge to ward. There were no significant differences in short term outcomes and 1-year survival in critically ill cancer patients whose readmissions were preventable or not. PMID- 29796147 TI - Feasibility study of minimally trained medical students using the Rural Obstetrical Ultrasound Triage Exam (ROUTE) in rural Panama. AB - BACKGROUND: Maternal and infant mortality rates reported in rural Panama are greater than those in urban regions. Bocas del Toro is a region of Panama inhabited by indigenous people at greater risk for pregnancy-related complications and deaths due to geographic isolation and limited access to health care. Portable ultrasound training programs have recently been implemented in low resource settings to increase access to diagnostic imaging. The goal of this study is to determine the feasibility of teaching first-year medical students the Rural Obstetrical Ultrasound Triage Exam (ROUTE) to help identify pathology in pregnant women of the Bocas del Toro region of Panama. METHODS: Eight first-year medical students completed ROUTE training sessions. After training, the students were compared to professional sonographers to evaluate their accuracy in performing the ROUTE. Students then performed the ROUTE in mobile clinics within Bocas del Toro. They enrolled women pregnant in their 2nd or 3rd trimesters and measured biparietal diameter, head circumference, amniotic fluid index, fetal lie and placental position. Any abnormal measurement would be further analyzed by the lead physician for a potential hospital referral. RESULTS: A total of 60 women were enrolled in the study. Four women were detected as having a possible high risk pregnancy and thus referred to a hospital for further evaluation. CONCLUSION: Based on our data, first-year medical students with additional training can use the ROUTE to identify complications in pregnancy using ultrasound in rural Panama. Additional studies are required to determine the optimal amount of training required for proficiency. PMID- 29796148 TI - Radial artery pseudoaneurysm diagnosed by point-of-care ultrasound five days after transradial catheterization: A case report. PMID- 29796149 TI - Obstructive shock secondary to fungal prosthetic aortic valve endocarditis. PMID- 29796151 TI - 2016 Annual Report of the University of Kansas Health System Poison Control Center. AB - Introduction: This is the 2016 Annual Report of the University of Kansas Health System Poison Control Center (PCC). The PCC is one of 55 certified poison control centers in the United States and serves the state of Kansas 24-hours a day, 365 days a year, with certified specialists in poison information and medical toxicologists. The PCC receives calls from the public, law enforcement, health care professionals, and public health agencies. All calls to the PCC are recorded electronically in the Toxicall(r) data management system and uploaded in near real-time to the National Poison Data System (NPDS), which is the data repository for all poison control centers in the United States. Methods: All encounters reported to the PCC from January 1, 2016 to December 31, 2016 were analyzed. Data recorded for each exposure includes caller location, age, weight, gender, substance exposed to, nature of exposure, route of exposure, interventions, medical outcome, disposition and location of care. Encounters were classified further as human exposure, animal exposure, confirmed non-exposure, or information call (no exposure reported). Results: The PCC logged 21,965 total encounters in 2016, including 20,713 human exposure cases. The PCC received calls from every county in Kansas. The majority of human exposure cases (50.4%, n = 10,174) were female. Approximately 67% (n = 13,903) of human exposures involved a child (defined as age 19 years or less). Most encounters occurred at a residence (94.0%, n = 19,476) and most calls (72.3%, n = 14,964) originated from a residence. The majority of human exposures (n = 18,233) were acute cases (exposures occurring over eight hours or less). Ingestion was the most common route of exposure documented (86.3%, n = 17,882). The most common reported substance in pediatric encounters was cosmetics/personal care products (n = 1,362), followed by household cleaning product (n = 1,301). For adult encounters, sedatives/hypnotics/antipsychotics (n = 1,130) and analgesics (n = 1,103) were the most frequently involved substances. Unintentional exposures were the most common reason for exposures (81.3%, n = 16,836). Most encounters (71.1%, n = 14,732) were managed in a non-healthcare facility (i.e., a residence). Among human exposures, 14,679 involved exposures to pharmaceutical agents while 10,176 involved exposure to non-pharmaceuticals. Medical outcomes were 32% (n = 6,582) no effect, 19% (n = 3,911) minor effect, 8% (n = 1,623) moderate effect, and 2% (n = 348) major effects. There were 15 deaths in 2016 reported to the PCC. Number of exposures, calls from healthcare facilities, cases with moderate or major medical outcomes, and deaths all increased in 2016 compared to 2015. Conclusion: The results of the 2016 University of Kansas Health System Poison Control annual report demonstrates that the center receives calls from the entire state of Kansas totaling over 20,000 human exposures per year. While pediatric exposures remain the most common, there is an increasing number of calls from healthcare facilities and for cases with serious outcomes. The experience of the PCC is similar to national data. This report supports the continued value of the PCC to both public and acute health care in the state of Kansas. PMID- 29796150 TI - High burden of atopy in immigrant families in substandard apartments in Sweden - on the contribution of bad housing to poor health in vulnerable populations. AB - Background: Atopic disorders are a global concern. Studies in migrant populations can illuminate the interplay of genetic and environmental factors. Exposures related to bad housing (indoor dampness, mould growth, crowding etc.) are likely to play a role in how socioeconomic inequalities can turn into health disparities for disadvantaged populations. The sizable immigrant population living in very poor-quality housing in Malmo, Sweden, became the focus of a cross-sectional study. Objective: To describe atopic disorders and sensitizations in a population living in substandard housing in Malmo, Sweden, with an emphasis on their relation to harmful exposures from the built environment. Methods: Families were recruited via identification of any children with symptomatic airway afflictions from health care records, and also asymptomatic children from school lists. Interviewer-led health questionnaire data and data from self-reports about living conditions were obtained together with data from home inspections carried out by health communicators. Families underwent skin prick tests (SPT) against common aeroallergens. Results: As could be expected from background demographic information, it turned out that we effectively studied an immigrant population inhabiting very precarious housing outside the center of Malmo. A total of 359 children from 130 families (total 650 participants) were included. Overall the prevalence of potentially harmful environmental exposures was high (signs of moisture or mould in more than 50% of apartments, indoor smoking in 37% of households). Atopic disorders were common among both adults and children. SPTs showed a spectrum of sensitizations consistent with unselected populations in Sweden. Paternal sensitization in the SPT was associated with higher risk of sensitization for offspring than maternal sensitization. Few statistically significant associations of atopic sensitization with studied environmental exposures were detected (for example objective signs of dampness /mould in bathrooms). There were marked discrepancies between asthma diagnoses obtained from the health records and parental reports of such diagnoses and treatment for their children. Conclusions: The atopic burden in this selected immigrant population was high, and results point to unmet medical needs. Health care systems caring for such populations need to be aware of their specific health needs; comprehensive asthma and allergy care should include consideration of harmful environmental exposures, adhering to the precautionary principle. PMID- 29796152 TI - Increasing Onshore Oil Production: An Unexpected Explosion in Trauma Patients. AB - Introduction: Few data currently exist which are focused on type and severity of onshore oil extraction-related injuries. The purpose of this study was to evaluate injury patterns among onshore oil field operations. Methods: A retrospective review was conducted of all trauma patients aged 18 and older with an onshore oil field-related injury admitted to an American College of Surgeons verified level 1 trauma center between January 1, 2003 and June 30, 2012. Data collected included demographics, injury severity and details, hospital outcomes, and disposition. Results: A total of 66 patients met inclusion criteria. All patients were male, of which the majority were Caucasian (81.8%, n = 54) with an average age of 36.5 +/- 11.8 years, injury severity score of 9.4 +/- 8.9, and Glasgow Coma Scale score of 13.8 +/- 3.4. Extremity injuries were the most common (43.9%, n = 29), and most were the result of being struck by an object (40.9%, n = 27). Approximately one-third of patients (34.8%, n = 23) were admitted to the intensive care unit. Nine patients (13.6%) required mechanical ventilation while 27 (40.9%) underwent operative treatment. The average hospital length of stay was 5.8 +/- 16.6 days, and most patients (78.8%, n = 52) were discharged home. Four patients suffered permanent disabilities, and there were two deaths. Conclusion: Increased domestic onshore oil production inevitably will result in higher numbers of oil field-related traumas. By focusing on employees who are at the greatest risk for injuries and by targeting the main causes of injuries, training programs can lead to a decrease in injury incidence. PMID- 29796153 TI - Head CT Guidelines Following Concussion among the Youngest Trauma Patients: Can We Limit Radiation Exposure Following Traumatic Brain Injury? AB - Introduction: Recent studies have provided guidelines on the use of head computed tomography (CT) scans in pediatric trauma patients. The purpose of this study was to identify the prevalence of these guidelines among concussed pediatric patients. Methods: A retrospective review was conducted of patients four years or younger with a concussion from blunt trauma. Demographics, head injury characteristics, clinical indicators for head CT scan (severe mechanism, physical exam findings of basilar skull fracture, non-frontal scalp hematoma, Glasgow Coma Scale score, loss of consciousness, neurologic deficit, altered mental status, vomiting, headache, amnesia, irritability, behavioral changes, seizures, lethargy), CT results, and hospital course were collected. Results: One-hundred thirty-three patients (78.2%) received a head CT scan, 7 (5.3%) of which demonstrated fractures and/or bleeds. All patients with skull fractures and/or bleeds had at least one clinical indicator present on arrival. Clinical indicators that were observed more commonly in patients with positive CT findings than in those with negative CT findings included severe mechanism (100% vs. 54.8%, respectively, p = 0.020) and signs of a basilar skull fracture (28.6% vs. 0.8%, respectively, p = 0.007). Severe mechanism alone was found to be sensitive, but not specific, whereas signs of a basilar skull fracture, headache, behavioral changes, and vomiting were specific, but not sensitive. No neurosurgical procedures were necessary, and there were no deaths. Conclusion: Clinical indicators were present in patients with positive and negative CT findings. However, severe mechanism of injury and signs of basilar skull fracture were more common for patients with positive CT findings. PMID- 29796154 TI - Evaluation of Protective Equipment Used Among Motorbike Riders. AB - Introduction: This study compared outcomes between patients injured at a motorbike track, which requires riders to follow safety equipment guidelines, and those involved in recreational riding where safety equipment usage is voluntary. Methods: A retrospective review was conducted of all patients presenting with motorbike-related injuries at an American College of Surgeons verified level-I trauma center between January 1, 2009 and December 31, 2013. Data collected included demographics, injury details, safety equipment use, hospitalization details, and discharge disposition. Comparisons were made regarding protective equipment usage. Results: Among the 115 patients admitted, more than half (54.8%, n = 63) were injured on a motorbike track, and 45.2% (n = 52) were injured in a recreational setting. The majority of patients were male (93.9%), Caucasian (97.4%), and between the ages of 18 to 54 (64.4%). Helmet usage was higher among track riders (95.2%, n = 60) than recreational riders (46.2%, n = 24, p < 0.0001). Comparisons of injury severity and outcomes between those who wore protective equipment and those who did not were not significant. Conclusion: Even though track riders wore protective equipment more than recreational riders, there was no difference between the groups regarding injury severity or hospital outcomes. These results suggested that motocross riders should not rely on protective equipment as the only measure of injury prevention. PMID- 29796155 TI - Elastic Abdominal Binders Reduce Cesarean Pain Postoperatively: A Randomized Controlled Pilot Trial. AB - Background: A potential non-pharmacologic way to reduce postoperative pain and bleeding is using an abdominal binder during postoperative recovery. This study aims to determine the effect an elastic abdominal binder has on postoperative pain and hemorrhage after cesarean delivery. Methods: A randomized, single-site, pilot trial was conducted at two prenatal care clinics and an academic hospital in Kansas. Beginning in April 2013, 60 patients were enrolled if delivering via cesarean. Participants were randomized to receive an abdominal binder or to a control group (did not use binder). Pain levels were reported by questionnaire one day after surgery using a 0 to 10 scale, with 10 being the worst pain. Patient characteristics and blood loss were assessed by medical record review. Results: Of the 56 patients completing the study, 29 (51.8%) were randomized to the binder group and 27 (48.2%) were randomized to the control group. The binder group reported significantly lower pain score (p = 0.019) and average pain score (p = 0.024). There was no difference in body mass index, age, previous surgery, infant birth weight, estimated blood loss, and average dose of pain medication during the first 24 hours after the cesarean delivery between the two groups. There was no difference in pre- and post-operative hemoglobin levels by treatment group (p = 0.406). Conclusions: Abdominal binders may be associated with improved postoperative pain scores but did not affect postoperative hemorrhage. PMID- 29796156 TI - Worse than the Disease? The Rash of Lomatium Dissectum. PMID- 29796157 TI - Metastasis of Benign Leiomyomas Outside the Uterus. PMID- 29796158 TI - SRC/ABL inhibition disrupts CRLF2-driven signaling to induce cell death in B-cell acute lymphoblastic leukemia. AB - Children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) overexpressing the CRLF2 gene (hiCRLF2) have poor prognosis. CRLF2 protein overexpression leads to activated JAK/STAT signaling and trials are underway using JAK inhibitors to overcome treatment failure. Pre-clinical studies indicated limited efficacy of single JAK inhibitors, thus additional pathways must be targeted in hiCRLF2 cells. To identify additional activated networks, we used single-cell mass cytometry to examine 15 BCP-ALL primary patient samples. We uncovered a coordinated signaling network downstream of CRLF2 characterized by co activation of JAK/STAT, PI3K, and CREB pathways. This CRLF2-driven network could be more effectively disrupted by SRC/ABL inhibition than single-agent JAK or PI3K inhibition, and this could be demonstrated even in primary minimal residual disease (MRD) cells. Our study suggests SCR/ABL inhibition as effective in disrupting the cooperative functional networks present in hiCRLF2 BCP-ALL patients, supporting further investigation of this strategy in pre-clinical studies. PMID- 29796159 TI - Analysis of KIT gene mutations in patients with melanoma of the head and neck mucosa: a retrospective clinical report. AB - Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) are more aggressive, and their prognostic markers have not been fully elucidated. This study, comprising 28 patients with HNMM, aimed to establish the relationship between different mutations and outcome, define the incidence of KIT mutations in HNMM, and identify the correlation among therapeutic options, histopathological findings, demographic data, and clinical response. Clinical analysis included patient characteristics, staging, primary and palliative treatments, and disease-free survival and overall survival (OS). Progression-free survival and OS were analyzed. Paraffin blocks were selected following histologic analyses, enabling DNA extraction. PCR amplification of exons 9, 11, 13, and 17, with different DNA concentrations, was performed. Patients were predominantly females (57%) and aged 27-85 years. All patients underwent surgery; 17 received adjuvant radiotherapy, and recurrences occurred in 82% patients. Oncologic mutations in KIT were found in 7 of 7 tumors, 3 in exon 9, 3 in exon 11, and 1 in exon 13. Predictive factors for recurrence were mitotic rate, vascular invasion, and perineural spread. There were no significant differences in DFS and OS according to KIT mutation. Our study results suggest that some patients might benefit from appropriate targeted therapy with kinase inhibitors. PMID- 29796160 TI - Comprehensive molecular analysis based on somatic copy number alterations in intramucosal colorectal neoplasias and early invasive colorectal cancers. AB - It is unclear whether somatic copy number alterations (SCNAs) contribute to the development of colorectal cancer (CRC). Here, we aimed to identify the molecular profiles of early colorectal carcinogenesis based on SCNAs and determine the associations of other molecular abnormalities for the detection of neoplasia in both intramucosal neoplasia (IMN) and invasive CRC with invasion into the muscular layer without metastasis (early invasive CRC). A single nucleotide polymorphism array was used to examine 100 colorectal IMNs (low-grade adenoma [LGA], 40; high-grade adenoma [HGA], 25; intramucosal adenocarcinoma [IMA], 35) and early invasive CRC (20 tumors). In addition, genetic mutations (KRAS, BRAF), TP53 overexpression, microsatellite instability (MSI), and DNA methylation (low, intermediate, high) were examined. Hierarchical clustering analysis based on the SCNA pattern was carried out to identify molecular profiles in IMNs and early invasive CRC. Colorectal tumors were classified into three subgroups based on SCNA patterns. Subgroup 1 was characterized by multiple SCNAs, subgroup 3 was closely associated with infrequent SCNAs, and subgroup 2 was an intermediate subgroup in SCNA pattern between subgroups 1 and 3. Although mutations in KRAS were commonly found in all three subgroups, overexpression of TP53 was observed primarily in subgroup 1 and 2. DNA methylation showed a low/intermediate type. Finally, no MSI was detected. Each subgroup was correlated with histology (subgroup 1, early invasive CRC; subgroup 2, LGA; subgroups 2 and 3, HGA and IMA). Considerable SCNAs may be required for acquisition of invasive ability in CRC. Our results provide novel insights into early CRC. PMID- 29796161 TI - Involvement of SNPs in miR-3117 and miR-3689d2 in childhood acute lymphoblastic leukemia risk. AB - Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Numerous studies have shown that microRNAs (miRNAs) could play a role in this disease. Nowadays, more than 2500 miRNAs have been described, that regulate more than 50% of genes, including those involved in B-cell maturation, differentiation and proliferation. Genetic variants in miRNAs can alter their own levels or function, affecting their target gene expression, and then, may affect ALL risk. Therefore, the aim of this study was to determine the role of miRNA genetic variants in B-ALL susceptibility. We analyzed all variants in pre-miRNAs (MAF > 1%) in two independent cohorts from Spain and Slovenia and inferred their functional effect by in silico analysis. SNPs rs12402181 in miR-3117 and rs62571442 in miR-3689d2 were associated with ALL risk in both cohorts, possibly through their effect on MAPK signalling pathway. These SNPs could be novel markers for ALL susceptibility. PMID- 29796162 TI - YdjC chitooligosaccharide deacetylase homolog induces keratin reorganization in lung cancer cells: involvement of interaction between YDJC and CDC16. AB - Lung cancer is a fatal disease with a high mortality rate. The perinuclear reorganization of keratin 8 (K8) is an important biochemical phenomenon reflecting changes in the physical properties of metastatic cancer. However, there is not much of information about the regulatory molecules involved in phosphorylation and perinuclear reorganization of K8. In this study, we investigated the role and molecular mechanisms of YdjC chitooligosaccha- ride deacetylase homolog (YDJC) in sphingosylphosphorylcholine (SPC)-induced phosphorylation and reorganization of K8, and migration and invasion (SPC-induced events). SPC induced expression of YDJC in a dose- and time-dependent manner. Gene silencing of YDJC suppressed SPC-induced events. YDJC overexpression induced the SPC-induced events. YDJC deacetylase dominant negative mutant (YDJCD13A) did not induce SPC-induced events. YDJC siRNA reduced ERK activation and overexpression of YDJC induced ERK activation. The siRNA of ERK1 or ERK2 suppressed YDJC-induced phosphorylation and reorganization of K8, and migration and invasion. Co-immunoprecipitation revealed that YDJC binds to CDC16. Interestingly, CDC16 siRNA induced SPC-induced events. Overexpression of CDC16 blocked SPC-induced events. KMPLOT analysis based on public microarray data revealed the poor prognosis of lung cancer patients with high expression of YDJC compared with patients with low expression of YDJC. The collective results indicate that YDJC is involved in SPC-induced events in A549 lung cancer cells by interacting with CDC16. YDJC overexpression might be involved in the progression of lung cancer. These results also suggest that suppression of YDJC or boosting of CDC16 interaction with YDJC might be a novel way to prevent progression of lung cancer. PMID- 29796163 TI - Disturbed alternative splicing of FIR (PUF60) directed cyclin E overexpression in esophageal cancers. AB - Overexpression of alternative splicing of far upstream element binding protein 1 (FUBP1) interacting repressor (FIR; poly(U) binding splicing factor 60 [PUF60]) and cyclin E were detected in esophageal squamous cell carcinomas (ESCC). Accordingly, the expression of FBW7 was examined by which cyclin E is degraded as a substrate via the proteasome system. Expectedly, FBW7 expression was decreased significantly in ESCC. Conversely, c-myc gene transcriptional repressor FIR (alias PUF60; U2AF-related protein) and its alternative splicing variant form (FIRDeltaexon2) were overexpressed in ESCC. Further, anticancer drugs (cis diaminedichloroplatinum/cisplatin [CDDP] or 5-fluorouracil [5-FU]) and knockdown of FIR by small interfering RNA (siRNA) increased cyclin E while knockdown of FIRDeltaexon2 by siRNA decreased cyclin E expression in ESCC cell lines (TE1, TE2, and T.Tn) or cervical SCC cells (HeLa cells). Especially, knockdown of SAP155 (SF3b1), a splicing factor required for proper alternative splicing of FIR pre-mRNA, decreased cyclin E. Therefore, disturbed alternative splicing of FIR generated FIR/FIRDeltaexon2 with cyclin E overexpression in esophageal cancers, indicating that SAP155 siRNA potentially rescued FBW7 function by reducing expression of FIR and/or FIRDeltaexon2. Remarkably, Three-dimensional structure analysis revealed the hypothetical inhibitory mechanism of FBW7 function by FIR/FIRDeltaexon2, a novel mechanism of cyclin E overexpression by FIR/FIRDeltaexon2-FBW7 interaction was discussed. Clinically, elevated FIR expression potentially is an indicator of the number of lymph metastases and anti FIR/FIRDeltaexon2 antibodies in sera as cancer diagnosis, indicating chemical inhibitors of FIR/FIRDeltaexon2-FBW7 interaction could be potential candidate drugs for cancer therapy. In conclusion, elevated cyclin E expression was, in part, induced owing to potential FIR/FIRDeltaexon2-FBW7 interaction in ESCC. PMID- 29796166 TI - Carbon ion radiotherapy for inoperable pediatric osteosarcoma. AB - Background: Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments. Results: Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5-20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT. Conclusions: CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments. Methods: We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014. PMID- 29796164 TI - Using antibody directed phototherapy to target oesophageal adenocarcinoma with heterogeneous HER2 expression. AB - Early oesophageal adenocarcinoma (OA) and pre-neoplastic dysplasia may be treated with endoscopic resection and ablative techniques such as photodynamic therapy (PDT). Though effective, discrete areas of disease may be missed leading to recurrence. PDT further suffers from the side effects of off-target photosensitivity. A tumour specific and light targeted therapeutic agent with optimised pharmacokinetics could be used to destroy residual cancerous cells left behind after resection. A small molecule antibody-photosensitizer conjugate was developed targeting human epidermal growth factor receptor 2 (HER2). This was tested in an in vivo mouse model of human OA using a xenograft flank model with clinically relevant low level HER2 expression and heterogeneity. In vitro we demonstrate selective binding of the conjugate to tumour versus normal tissue. Light dependent cytotoxicity of the phototherapy agent in vitro was observed. In an in vivo OA mouse xenograft model the phototherapy agent had desirable pharmacokinetic properties for tumour uptake and blood clearance time. PDT treatment caused tumour growth arrest in all the tumours despite the tumours having a clinically defined low/negative HER2 expression level. This new phototherapy agent shows therapeutic potential for treatment of both HER2 positive and borderline/negative OA. PMID- 29796167 TI - Combination of two anti-tubulin agents, eribulin and paclitaxel, enhances anti tumor effects on triple-negative breast cancer through mesenchymal-epithelial transition. AB - Improved prognosis for triple-negative breast cancer (TNBC) has currently plateaued and the development of novel therapeutic strategies is required. Therefore, we aimed to explore the anti-tumor effect of eribulin and paclitaxel combination therapy for TNBC. The effect of eribulin and paclitaxel in combination was tested, with both concurrent and sequential administration, using four TNBC cell lines (MDA-MB-231, Hs578T, MDA-MB-157, and Mx-1) in vitro and in an MDA-MB-231 BALB/c-nu/nu mouse xenograft model. The expression of epithelial mesenchymal phenotypic markers was analyzed by western blotting and immunohistochemical analyses. Simultaneous administration of eribulin and paclitaxel resulted in a synergistic anti-tumor effect with MDA-MB-231 and Hs578T cells, but not MDA-MB-157 and Mx-1 cells, in vitro. Moreover, pre-treatment with one drug significantly enhanced sensitivity to the subsequently administrated second drug in MDA-MB-231 and Hs578T cells. Eribulin increased E-cadherin expression and decreased the expression of mesenchymal markers in MDA-MB-231 and Hs578T cells. In contrast, paclitaxel increased the expression of mesenchymal markers. When epithelial-mesenchymal transition was induced by TGF-beta1, eribulin sensitivity was enhanced. In contrast, a TGF-beta receptor kinase inhibitor decreased eribulin sensitivity. In MDA-MB-231 tumor-bearing mice, concurrent administration of low doses of eribulin and paclitaxel significantly inhibited tumor growth compared to that with either monotherapy. Moreover, single administration of eribulin before the initiation of paclitaxel treatment decreased vimentin expression and reduced the average tumor volume in a mouse xenograft model. Eribulin and paclitaxel show synergistic anti-tumor effect by altering the epithelial-mesenchymal phenotype. This combination therapy could represent a novel therapeutic strategy for TNBC. PMID- 29796168 TI - Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma. AB - Sunitinib is a standard molecular-targeted drug used as a first-line treatment for metastatic clear cell renal cell carcinoma (ccRCC); however, resistance to sunitinib has become a major problem in medical practice. Recently, bromodomain containing 4 (BRD4), a member of the bromodomain family proteins, was identified as a promising therapeutic target, and its inhibitor JQ1 has been shown to have inhibitory effects in various human cancers. However, the anti-cancer effects of JQ1 in ccRCC, particularly sunitinib-resistant ccRCC, are still unclear. Here, we aimed to elucidate the anti-cancer effects of JQ1 and the mechanisms underlying BRD4 inhibition in sunitinib-sensitive and -resistant ccRCCs. Analysis of The Cancer Genome Atlas (TCGA) ccRCC cohort showed that patients with high BRD4 expression had shorter overall survival than those with low expression. JQ1 treatment significantly inhibited tumor growth of sunitinib-sensitive and resistant ccRCC cells in part through MYC regulation. Based on RNA sequencing analyses of ccRCC cells treated with JQ1 to elucidate the mechanisms other than MYC regulation, we identified several oncogenes that may be potential therapeutic targets or prognostic markers; patients with high expression of SCG5, SPOCD1, RGS19, and ARHGAP22 had poorer overall survival than those with low expression in TCGA ccRCC cohort. Chromatin immunoprecipitation assays revealed that these oncogenes may be promising BRD4 targets, particularly in sunitinib-resistant ccRCC cells. These results identified SCG5, SPOCD1, RGS19, and ARHGAP22 as potential prognostic markers and showed that BRD4 inhibition may have applications as a potential therapeutic approach in sunitinib-sensitive and resistant ccRCC. PMID- 29796165 TI - Preclinical evaluation of a GFRA1 targeted antibody-drug conjugate in breast cancer. AB - Despite recent advances in treatment, breast cancer remains the second-most common cause of cancer death among American women. A greater understanding of the molecular characteristics of breast tumors could ultimately lead to improved tumor-targeted treatment options, particularly for subsets of breast cancer patients with unmet needs. Using an unbiased genomics approach to uncover membrane-localized tumor-associated antigens (TAAs), we have identified glial cell line derived neurotrophic factor (GDNF) family receptor alpha 1 (GFRA1) as a breast cancer TAA. Immunohistochemistry (IHC) revealed that GFRA1 displays a limited normal tissue expression profile coupled with overexpression in specific breast cancer subsets. The cell surface localization as determined by fluorescence-activated cell sorting (FACS) and the rapid internalization kinetics of GFRA1 makes it an ideal target for therapeutic exploitation as an antibody drug conjugate (ADC). Here, we describe the development of a pyrrolobenzodiazepine (PBD)-armed, GFRA1-targeted ADC that demonstrates cytotoxicity in GFRA1-positive cell lines and patient-derived xenograft (PDX) models. The safety profile of the rat cross-reactive GFRA1-PBD was assessed in a rat toxicology study to find transient cellularity reductions in the bone marrow and peripheral blood, consistent with known off-target effects of PBD ADC's. These studies reveal no evidence of on-target toxicity and support further evaluation of GFRA1-PBD in GFRA1-positive tumors. PMID- 29796169 TI - Aberrant ATRX protein expression is associated with poor overall survival in NF1 MPNST. AB - Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive soft tissue sarcomas that can occur sporadically or in the setting of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. These tumors carry a dismal overall survival. Previous work in our lab had identified ATRX chromatin remodeler (ATRX), previously termed, Alpha Thalassemia/Mental Retardation Syndrome X Linked as a gene mutated in a subset of MPNSTs. Given the great need for novel biomarkers and therapeutic targets for MPNSTs, we sought to determine the expression of ATRX in a larger subset of sporadic and NF1 associated MPNSTs (NF1 MPNSTs). We performed immunohistochemistry (IHC) on 74 MPNSTs (43 NF1-associated and 31 sporadic), 21 plexiform neurofibromas, and 9 atypical neurofibromas. Using this approach, we have demonstrated that 58% (43/74) of MPNSTs have aberrant ATRX expression (<80% nuclear expression) compared to only 7% (2/30) of benign (plexiform and atypical) neurofibromas. Second, we demonstrated that 65% (28/43) of NF1-MPNSTs displayed aberrant ATRX expression as did 48% (15/31) of sporadic MPNSTs. Finally, we show that aberrant ATRX expression was associated with a significantly decreased overall survival for patients with NF1-MPNST (median OS of 17.9 months for aberrant expression and median OS not met (>120 months) for intact expression, p = 0.0276). In summary, we demonstrate that ATRX is aberrantly expressed in the majority of NF1-MPNSTs, but not plexiform or atypical neurofibromas. Additionally, aberrant ATRX expression is associated with decreased overall survival in NF1-MPNST, but not sporadic MPNST and may serve as a prognostic marker for patients with NF1-MPNST. PMID- 29796171 TI - Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma. AB - Objectives: To develop a surveillance protocol with improved cost-effectiveness after radical nephroureterectomy (RNU), as the cost-effectiveness of oncological surveillance after RNU remains unclear. Results: Of 426 patients, 109 (26%) and 113 (27%) experienced visceral and intravesical recurrences, respectively. The pathology-based protocol found significant differences in recurrence-free survival in the visceral recurrence but not in the intravesical recurrence. The medical costs per visceral recurrence detected were high, especially in normal risk (<= pT2N0, LVI-, SM-) patients. We developed a risk score associated with visceral recurrence using Cox regression analysis. The risk score-based protocol was significantly more cost-effective than the pathology-based protocol. Estimated cost differences reached $747,929 per recurrence detected, a suggested 55% reduction. Materials and Methods: We retrospectively evaluated 426 patients with RNU for upper tract urothelial carcinoma (UTUC) without distant metastasis at 4 hospitals. Patients with routine oncological follow-up were stratified into normal-, high- and very high-risk groups according to a pathology-based protocol utilizing pathological stage, lymphovascular invasion (LVI) and surgical margin (SM). Cost-effectiveness of the pathology-based protocol was evaluated, and a risk score-based protocol was developed to optimize cost-effectiveness. Risk scores were calculated by summing up risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate- and high-risk score. Estimated cost per recurrence detected by pathology-based and risk score-based protocols was compared. Conclusions: A risk score-stratified surveillance protocol has the potential to reduce over investigation during follow-up, making surveillance more cost-effective. PMID- 29796170 TI - Targeting the spliceosome for cutaneous squamous cell carcinoma therapy: a role for c-MYC and wild-type p53 in determining the degree of tumour selectivity. AB - We show that suppression of the spliceosome has potential for the treatment of cutaneous squamous cell carcinoma (cSCC). The small-molecule inhibitors of the spliceosome at the most advanced stage of development target the splicing factor SF3B1/SF3b155. The majority of cSCC cell lines are more sensitive than normal skin cells to death induced by the SF3B1 inhibitor pladienolide B. Knockdown of SF3B1 and a range of other splicing factors with diverse roles in the spliceosome can also selectively kill cSCC cells. We demonstrate that endogenous c-MYC participates in conferring sensitivity to spliceosome inhibition. c-MYC expression is elevated in cSCC lines and its knockdown reduces alterations in mRNA splicing and attenuates cell death caused by interference with the spliceosome. In addition, this study provides further support for a key role of the p53 pathway in the response to spliceosome disruption. SF3B1 inhibition causes wild-type p53 upregulation associated with altered mRNA splicing and reduced protein expression of both principal p53 negative regulators MDMX/MDM4 and MDM2. We observed that wild-type p53 can promote pladienolide B-induced death in tumour cells. However, p53 is commonly inactivated by mutation in cSCCs and p53 participates in killing normal skin cells at high concentrations of pladienolide B. This may limit the therapeutic window of SF3B1 inhibitors for cSCC. We provide evidence that, while suppression of SF3B1 has promise for treating cSCCs with mutant p53, inhibitors which target the spliceosome through SF3B1-independent mechanisms could have greater cSCC selectivity as a consequence of reduced p53 upregulation in normal cells. PMID- 29796172 TI - Oncodriver inhibition and CD4+ Th1 cytokines cooperate through Stat1 activation to induce tumor senescence and apoptosis in HER2+ and triple negative breast cancer: implications for combining immune and targeted therapies. AB - In patients with HER2-expressing breast cancer many develop resistance to HER2 targeted therapies. We show that high and intermediate HER2-expressing cancer cell lines are driven toward apoptosis and tumor senescence when treated with either CD4+ Th1 cells, or Th1 cytokines TNF-alpha and IFN-gamma, in a dose dependent manner. Depletion of HER2 activity by either siRNA or trastuzumab and pertuzumab, and subsequent treatment with either anti-HER2 Th1 cells or TNF-alpha and IFN-gamma resulted in synergistic increased tumor senescence and apoptosis in cells both sensitive and cells resistant to trastuzumab which was inhibited by neutralizing anti-TNF-alpha and IFN-gamma. Th1 cytokines induced minimal senescence or apoptosis in triple negative breast cancer cells (TNBC); however, inhibition of EGFR in combination with Th1 cytokines sensitized those cells causing both senescence and apoptosis. TNF-alpha and IFN-gamma led to increased Stat1 phosphorylation through serine and tyrosine sites and a compensatory reduction in Stat3 activation. Single agent IFN-gamma enhanced Stat1 phosphorylation on tyrosine 701 and similar effects were observed in combination with TNF-alpha and EGFR inhibition. These results demonstrate Th1 cytokines and anti-oncodriver blockade cooperate in causing tumor senescence and apoptosis in TNBC and HER2-expressing breast cancer, suggesting these combinations could be explored as non-cross-reactive therapy preventing recurrence in breast cancer. PMID- 29796174 TI - Abundance of TRAIL attenuated by HIF2alpha and c-FLIP affects malignancy in renal cell carcinomas. AB - Dormant cancer cells are starvation-resistant leading to problems in the management of cancer. In renal cell carcinomas (RCCs), starvation-resistant cells are resistant to various currently available therapies. However, targeting hypoxia inducible factor 2-alpha (HIF2-alpha) induces cell death in dormant like/starvation-resistant RCCs. This study showed that the apoptotic cell death caused by tumor necrosis factor (TNF)-related apoptosis-induced ligand (TNFSF10/TRAIL) was attenuated by CASP8 and FADD-like apoptosis regulator (CFLAR/c-FLIP) following HIF2-alpha activation, despite the high expression of TRAIL in such RCCs. Knockdowns of TRAIL averted apoptotic cell death caused by HIF2-alpha inhibition in starvation-resistant RCCs. Knockdowns of both HIF2-alpha and c-FLIP augmented apoptotic cell death, whereas overexpression of c-FLIP completely averted apoptosis. In addition, high abundance of TRAIL was correlated with poor prognosis in patients with RCC, suggesting that TRAIL, followed by HIF2 alpha and c-FLIP, play a role in the survival and/or progression of malignant RCCs. PMID- 29796173 TI - Metabolomics based predictive classifier for early detection of pancreatic ductal adenocarcinoma. AB - The availability of robust classification algorithms for the identification of high risk individuals with resectable disease is critical to improving early detection strategies and ultimately increasing survival rates in PC. We leveraged high quality biospecimens with extensive clinical annotations from patients that received treatment at the Medstar-Georgetown University hospital. We used a high resolution mass spectrometry based global tissue profiling approach in conjunction with multivariate analysis for developing a classification algorithm that would predict early stage PC with high accuracy. The candidate biomarkers were annotated using tandem mass spectrometry. We delineated a six metabolite panel that could discriminate early stage PDAC from benign pancreatic disease with >95% accuracy of classification (Specificity = 0.85, Sensitivity = 0.9). Subsequently, we used multiple reaction monitoring mass spectrometry for evaluation of this panel in plasma samples obtained from the same patients. The pattern of expression of these metabolites in plasma was found to be discordant as compared to that in tissue. Taken together, our results show the value of using a metabolomics approach for developing highly predictive panels for classification of early stage PDAC. Future investigations will likely lead to the development of validated biomarker panels with potential for clinical translation in conjunction with CA-19-9 and/or other biomarkers. PMID- 29796175 TI - A targeted transforming growth factor-beta (TGF-beta) blocker, TTB, inhibits tumor growth and metastasis. AB - Transforming growth factor beta (TGF-beta) promotes cancer growth in late stage cancers. To inhibit the TGF-beta pathway, we investigated a tumor-targeting TGF beta receptor blocker, TTB, and its role in tumor progress. The targeted TTB comprised of the extracellular domain of the TGF-beta receptor II, the endoglin domain of TGF-beta receptor III, and the human immuno-globin IgG1 constant fragment (Fc). To enhance tumor microenvironment targeting, a RGD peptide was fused at the N-terminal of TTB. The targeted TTB exhibited potent TGF-beta neutralization activities, and inhibited cancer cell migration and invasion as well as colony formation. In xenograft models, the TTB had potent tumor inhibition activities. The TTB also attenuated the TGF-beta1-induced Smad2 phosphorylation and epithelial to mesenchymal transformation (EMT), and suppressed breast cancer metastasis. Thus, the TTB is an effective TGF-beta blocker with a potential for blocking excessive TGF-beta induced pathogenesis in vivo. PMID- 29796176 TI - Association of increased primary breast tumor AGR2 with decreased disease specific survival. AB - Objective: Tumor expression of Anterior Gradient 2 (AGR2), an endoplasmic reticulum protein disulfide isomerase, was associated with decreased breast cancer survival. We aimed to validate the association of tumor AGR2 mRNA expression with disease-specific survival (DSS) and identify differentially expressed signaling pathways between high and low AGR2 expression tumor groups. Methods: Primary tumor mRNA expression data from the METABRIC study was used to evaluate AGR2 expression as a prognostic factor for DSS while adjusting for survival-determining confounders using Cox proportional-hazards regression. Differentially expressed genes and signaling pathway differences between high and low AGR2 groups were determined by modular enrichment analyses using DAVID and Ingenuity Pathway Analysis. Results: Increased tumor AGR2 mRNA expression was associated with decreased DSS among 1,341 women (per each standard deviation increase of AGR2 expression: HR 1.14, 95% CI: 1.01-1.29, P = 0.03). Pathway analyses supported prior experimental studies showing that estrogen receptor 1 (ESR1) regulated AGR2 expression. Canonical signaling pathways significantly differentially represented between high and low AGR2 groups included those involved in inflammation and immunity. Conclusion: Increased primary tumor AGR2 expression was associated with decreased DSS. Pathway analyses suggested that increased AGR2 was associated with endoplasmic reticular homeostasis, possibly allowing tumor cells to overcome hypoxic stress and meet the increased protein demand of tumorigenesis, thereby preventing unfolded protein response-mediated apoptosis. PMID- 29796177 TI - Differential prognostic impact of interleukin-34 mRNA expression and infiltrating immune cell composition in intrinsic breast cancer subtypes. AB - Interleukin-34 (IL-34) is a ligand for the CSF-1R and has also two additional receptors, PTPRZ1 and syndecan-1. IL-34 plays a role in innate immunity, inflammation, and cancer. However, the role of IL-34 in breast cancer is still ill-defined. We analyzed IL-34 mRNA expression in breast cancer cell lines and breast cancer patients and applied established computational approaches (CIBERSORT, ESTIMATE, TIMER, TCIA), to analyze gene expression data from The Cancer Genome Atlas (TCGA). Expression of IL-34 was associated with a favorable prognosis in luminal and HER2 but not basal breast cancer patients. Gene expression of CSF-1 and CSF-1R was strongly associated with myeloid cell infiltration, while we found no or only weak correlations between IL-34, PTPRZ1, syndecan-1 and myeloid cells. In vitro experiments showed that tyrosine phosphorylation of CSF-1R, ERK, and FAK and cell migration are differentially regulated by IL-34 and CSF-1 in breast cancer cell lines. Collectively, our data suggest that correlation of IL-34 gene expression with survival is dependent on the molecular breast cancer subtype. Furthermore, IL-34 is not associated with myeloid cell infiltration and directly regulates breast cancer cell migration and signaling. PMID- 29796179 TI - Preoperative tumor size is associated with deep myometrial invasion and lymph node metastases and is a negative prognostic indicator for patients with endometrial carcinoma. AB - We examined the usefulness of evaluating tumor size determined using preoperative magnetic resonance imaging (MRI) for prognosis in patients with endometrial carcinoma (EC). Patients (N = 184) with EC who underwent surgery at Shimane University Hospital between 1997 and 2013 were enrolled. We investigated the association between the tumor size of EC assessed prior to surgery by MRI (anteroposterior [AP], transverse [TV], and craniocaudal [CC] diameters) and various clinical parameters including deep myometrial invasion and lymph node metastases. We subsequently examined the prognostic significance of tumor size in patients with EC. Survival analysis was performed using the Kaplan-Meier method, and prognostic factors were evaluated using the Cox's proportional hazards regression model. Multivariate analysis identified increased AP diameter as an independent negative prognostic factor for overall survival (OS) (P = 0.037). A long AP diameter has prognostic value and the potential to be a predictive marker for surgical outcomes in patients with EC. Furthermore, AP diameter exhibited the greatest area under the curve (AUC) (0.727) for deep myometrial invasion, and CC diameter had the greatest AUC for lymph node metastases (0.854). Evaluation of tumor size parameters may aid in the identification of high-risk populations, which could improve treatment selection and patient outcomes. PMID- 29796178 TI - SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. AB - Activation of the p38 mitogen-activated protein kinase (MAPK) pathway has been implicated in various detrimental events finally leading to endothelial dysfunction. The present study therefore investigates the impact of the p38 MAPK inhibitor SB202190 on the expression of the cytoprotective enzyme heme oxygenase 1 (HO-1) as well as metabolic activity, apoptosis and autophagy of endothelial cells. Using human umbilical vein endothelial cells (HUVEC) SB202190 was found to cause a time- and concentration-dependent induction of HO-1 protein. Induction of HO-1 protein expression was mimicked by SB203580, another p38 MAPK inhibitor, but not by SB202474, an inactive structural analogue of p38 MAPK inhibitors. HO-1 induction by both SB202190 and SB203580 was also demonstrated by analysis of mRNA expression. On the functional level, SB202190 was shown to increase metabolic activity and autophagy of HUVEC along with diminishing basal apoptosis. Treatment of cells with tin protoporphyrin IX (SnPPIX), a well-characterised HO-1 enzymatic inhibitor, or HO-1 siRNA left SB202190-modulated metabolic activity and autophagy virtually unaltered but caused a significant reversal of the anti-apoptotic action of SB202190. Conversely, however, HO-1 expression by SB202190 became completely suppressed by the autophagy inhibitor bafilomycin A1. Bafilomycin A1 likewise fully reversed effects of SB202190 on metabolic activity and apoptosis, albeit significantly inducing apoptosis per se. Collectively, this work demonstrates SB202190 to confer upstream induction of autophagy followed by HO-1 induction resulting in potential protective effects against apoptosis. On the other hand, our data oppose HO-1 to contribute to SB202190-mediated increases in metabolic activity and autophagy, respectively. PMID- 29796180 TI - Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients. AB - There had been several studies using gene-expression profiling in predicting distant recurrence in breast cancer. In this study, we developed an 18-gene classifier (18-GC) to predict distant recurrence of breast cancer and compared it with the 21-gene panel (Oncotype DX(r), ODx) in performance. Included were 224 breast cancer patients with positive hormonal receptor (HR+) and negative human epidermal growth factor receptor 2 (HER2-). We compared the demographic, clinical, and survival information of the patients, and further compared the prediction of recurrence risk obtained by using the 18-GC with that by ODx. To have the best combined sensitivity and specificity, receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff values for several breakpoint scores. For the new 18-GC, a breakpoint score of 21 was adopted to produce a combined highest sensitivity (95%) and specificity (39%) in detecting distant recurrence. At this breakpoint score, 164 of the 224 patients were classified by the 18-GC in the same risk level as by ODx, giving a concordance rate of 73%. Along with patient age and tumor stage, this 18-GC was found to be an independent significant prognostic factor of distant metastasis of breast cancer. We have thus created a new gene panel assay for prediction of distant recurrence in HR+ and HER2- breast cancer patients. With a high concordance rate with ODx, this new assay may serve as a good tool for individual breast cancer patients to make an informed decision on whether adjuvant chemotherapy should be performed post-surgery. PMID- 29796182 TI - DGC-specific RHOA mutations maintained cancer cell survival and promoted cell migration via ROCK inactivation. AB - RHOA missense mutations exist specifically in diffuse type gastric cancers (DGC) and are considered one of the DGC driver genes, but it is not fully understood how RHOA mutations contribute to DGC development. Here we examined how RHOA mutations affect cancer cell survival and cell motility. We revealed that cell survival was maintained by specific mutation sites, namely G17, Y42, and L57. Because these functional mutations suppressed MLC2 phosphorylation and actin stress fiber formation, we realized they act in a dominant-negative fashion against the ROCK pathway. Through the same inactivating mechanism that maintained cell survival, RHOA mutations also increased cell migration activity. Cell survival and migration studies on CLDN18-ARHGAP (CLG) fusions, which are known to be mutually exclusive to RHOA mutations, showed that CLG fusions complemented cell survival under RHOA knockdown condition and also induced cell migration. Site-directed mutagenesis analysis revealed the importance of the GAP domain and indicated that CLG fusions maintained RHOA in the inactive form. Taken together, these findings show that the inactivation of ROCK would be a key step in DGC development, so ROCK activation might provide novel therapeutic opportunities. PMID- 29796181 TI - RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry. AB - Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 proteins, the core components of the PCP pathway, due to impaired proteasomal activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an inhibitor of sarcoendoplasmic reticulum Ca2+- ATPases, showed impaired store operated Ca2+ entry (SOCE), which is mediated by STIM1 and Orai1 proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR protein complex is required for regulating proteasomal activity and for modulating SOCE, which may contribute to the ciliopathy phenotype. PMID- 29796183 TI - PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer. AB - Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the PRKD1 gene. PKD1 has been previously shown to be a prognostic factor in ERalpha+ tamoxifen resistant breast tumors and PKD1 overexpression confers estrogen independence to ERalpha+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed PRKD1 mRNA levels in 527 primary breast tumors. We found that high PRKD1 mRNA levels were significantly and independently associated with a low metastasis free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically. High PRKD1 mRNA levels were also associated with a low overall survival in TNBC. We identified novel PKD1 inhibitors and assessed their antitumor activity in vitro in TNBC cell lines and in vivo in a TNBC patient-derived xenograft (PDX) model. Pharmacological inhibition and siRNA-mediated depletion of PKD1 reduced colony formation in MDA MB-436 TNBC cells. PKD1 inhibition also reduced tumor growth in vivo in a TNBC PDX model. Together, these results establish PKD1 as a poor prognostic factor and a potential therapeutic target in TNBC. PMID- 29796186 TI - miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation. AB - Although the oncogene MMSET (also known as NSD2 or WHSC1) has an essential role in malignancies, its impact on human endometrial cancer (EC) metastasis and the molecular mechanism of MMSET regulation are largely unknown. We report that MMSET was markedly upregulated in EC cell lines and EC tissues, and was significantly associated with poor survival in EC. MMSET overexpression greatly promoted EC cell invasion and sphere formation, whereas inhibition of MMSET reduced EC cell invasion and sphere formation. Importantly, Twist1 was required for MMSET-induced EC cell invasion and sphere formation. Moreover, we demonstrate that miR-34a, miR 424 and miR-513 directly modulate MMSET expression to attenuate the invasion and sphere formation capacity of EC cells. miR-34a, miR-424 and miR-513 were down regulated in EC compared with normal tissue, and reduced expression of miR-34a, miR-424 and miR-513 was clinically associated with a poorer prognosis in EC patients. Furthermore, specific inhibition of MMET with BIX-01294 led to decreased EC cell invasion and impaired sphere formation. These findings suggest a pro-metastatic role for MMSET in EC and reveal that the repression of miR-34a, miR-424 and miR-513 contributes to the overexpression of MMSET during EC metastasis. PMID- 29796185 TI - Chloride intracellular channel 1 as a switch among tumor behaviors in human esophageal squamous cell carcinoma. AB - Background: Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; however, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study was to investigate the role of CLIC1 in human ESCC. Methods: CLIC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with CLIC1 siRNA, and their effects on cell proliferation, the cell cycle, apoptosis, migration, and invasion were analyzed. The gene expression profiles of cells were analyzed using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. Results: ESCC cells strongly expressed CLIC1. The depletion of CLIC1 using siRNA inhibited cell proliferation, induced apoptosis, and promoted cell migration and invasion. The results of the microarray analysis revealed that the depletion of CLIC1 regulated apoptosis via the TLR2/JNK pathway. Immunohistochemistry showed that CLIC1 was present in the cytoplasm of carcinoma cells, and that the very strong or very weak expression of CLIC1 was an independent poor prognostic factor. Conclusions: The present results suggest that the very strong expression of CLIC1 enhances tumor survival, while its very weak expression promotes cellular movement. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC. PMID- 29796187 TI - Cytokeratin 8/18 protects breast cancer cell lines from TRAIL-induced apoptosis. AB - TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis by engaging its death receptors (DRs) 4 and/or 5 on targeted cells. Clinical attempts to stimulate this apoptotic pathway for cancer therapy, including the use of recombinant human TRAIL (rhTRAIL) or receptor agonistic antibodies, have been underway for over a decade. Unfortunately, these agents have only shown limited therapeutic effects due largely to tumor resistance arising from mechanisms yet to be defined. Here we show that intermediate filament proteins, keratin 8 and keratin 18 (K8/K18), negatively regulate TRAIL induced apoptosis. K8/K18 protein levels are consistently higher in TRAIL-resistant cells compared to TRAIL sensitive cells in a panel of breast cancer cell lines. Blockade of K8 increased expression of DR5 on the surface of targeted cells and sensitized the cells to TRAIL-induced apoptosis. Conversely, ectopic expression of K8/K18 downregulated DR5 protein expression. K8/K18 appears to negatively regulate apoptosis signaling via DR5 in breast cancer cells. Our findings warrant additional studies to determine if K8/K18 could be a predictor of tumor resistance to DR5-targeted therapies. PMID- 29796184 TI - MAP4K4 controlled integrin beta1 activation and c-Met endocytosis are associated with invasive behavior of medulloblastoma cells. AB - Local tissue infiltration of Medulloblastoma (MB) tumor cells precedes metastatic disease but little is still known about intrinsic regulation of migration and invasion in these cells. We found that MAP4K4, a pro-migratory Ser/Thr kinase, is overexpressed in 30% of primary MB tumors and that increased expression is particularly associated with the frequently metastatic SHH beta subtype. MAP4K4 is a driver of migration and invasion downstream of c-Met, which is transcriptionally up-regulated in SHH MB. Consistently, depletion of MAP4K4 in MB tumor cells restricts HGF-driven matrix invasion in vitro and brain tissue infiltration ex vivo. We show that these pro-migratory functions of MAP4K4 involve the activation of the integrin beta-1 adhesion receptor and are associated with increased endocytic uptake. The consequent enhanced recycling of c-Met caused by MAP4K4 results in the accumulation of activated c-Met in cytosolic vesicles, which is required for sustained signaling and downstream pathway activation. The parallel increase of c-Met and MAP4K4 expression in SHH MB could predict an increased potential of these tumors to infiltrate brain tissue and cause metastatic disease. Molecular targeting of the underlying accelerated endocytosis and receptor recycling could represent a novel approach to block pro-migratory effector functions of MAP4K4 in metastatic cancers. PMID- 29796188 TI - The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells. AB - Altered glycolysis is a characteristic of many cancers, and can also be associated with changes in stem cell-like cancer (SCLC) cell populations. We therefore set out to directly examine the effect of glycolysis on SCLC cell phenotype, using a model where glycolysis is stably reduced by adapting the cells to a sugar source other than glucose. Restricting glycolysis using this approach consistently resulted in cells with increased oncogenic potential; including an increase in SCLC cells, proliferation in 3D matrigel, invasiveness, chemoresistance, and altered global gene expression. Tumorigenicity in vivo was also markedly increased. SCLC cells exhibited increased dependence upon alternate metabolic pathways. They also became c-KIT dependent, indicating that their apparent state of maturation is regulated by glycolysis. Single-cell mRNA sequencing identified altered networks of metabolic-, stem- and signaling- gene expression within SCLC-enriched populations in response to glycolytic restriction. Therefore, reduced glycolysis, which may occur in niches within tumors where glucose availability is limiting, can promote tumor aggressiveness by increasing SCLC cell populations, but can also introduce novel, potentially exploitable, vulnerabilities in SCLC cells. PMID- 29796189 TI - Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau. AB - Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations. PMID- 29796192 TI - The recognition of Chronobiology in Science. PMID- 29796191 TI - A case of ALK-rearranged non-small cell lung cancer that responded to ceritinib after development of resistance to alectinib. AB - The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non-small cell lung cancer (NSCLC) positive for ALK fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of ALK-rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with ALK-rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations. PMID- 29796190 TI - Cancer stem cells of hepatocellular carcinoma. AB - Hepatocellular carcinoma is a malignant tumor arising from hepatocytes. The hepatocellular carcinoma is dictated by a subset of cells with stem cell-like features. These cells are apoptosis-resistant and have particular biomarkers, which serve as seeds in different stages of tumorigenesis including initiation, progression, metastasis, and relapse of hepatocellular carcinoma. Signaling pathways of cancer stem cells are novel targets for the radical intervention of hepatocellular carcinoma. PMID- 29796193 TI - Effects of acute sleep deprivation and caffeine supplementation on anaerobic performance. AB - Purpose: Athletes involved in team sports may be subject to varying degrees of sleep deprivation either before or after training and competition. Despite the belief among athletes and coaches of the importance of adequate sleep for ensuing performance, the effect of sleep loss on team-sport anaerobic performance remains unclear. There is conflicting evidence in the scientific literature as to the impact of acute sleep deprivation and caffeine supplementation on anaerobic performance indices. The purpose of this study is to investigate the effect of 24 hours of acute sleep deprivation on anaerobic performance and the effect of caffeine supplementation on anaerobic performance in the sleep deprived state. Methods: 11 club level games players (n=11, 25+/-4 yr, 178+/-7.5 cm, 80.2+/-10.4 kg, 15.1+/-5.6% body fat) participated in a repeated measures double-blinded placebo control trial. Following familiarisation, each participant returned for testing on three separate occasions. One of the testing sessions took place following a night of normal sleep and the other two sessions took place following 24 hours of sleep deprivation with supplementation of either placebo or 6 mg.kg- 1 of caffeine. During each testing session participants performed the vertical jump height, 20-m straight sprint, Illinois speed agility test and 5-m shuttle run. Results: No significant differences were detected comparing non sleep deprived and sleep deprived interventions in any of the assessed outcome measures. There were also no significant differences observed in any of the outcome measures when comparing caffeine and placebo data in the sleep deprived state. Conclusion: In this cohort of athletes, a 24-h period of acute sleep deprivation did not have any significant impact on anaerobic performance. Caffeine also did not have any effect of on anaerobic performance in the sleep deprived state. PMID- 29796194 TI - Ambulatory positional obstructive sleep apnea syndrome. AB - Objective: To establish the prevalence of positional (PP) OSA patients using self administered home-based respiratory polygraphy (RP). Materials and Methods: 52 month retrospective study based on RP records. Results: 200 PR records: 70.5% men 29.5% women. 76% were diagnosed with OSA and 54.6% with PP OSA. There were no significant differences in Epworth Sleepiness Scale, apnea hypopnea index and oxygen desaturation index. PP OSA patients were younger, had a lower BMI (30.3+/ 0.9 vs. 35.3+/-1.2) (p<0.0001), and the time they spent with oxygen saturation <90% (T<90) was lower (8.8 vs. 28.7+/-6.7, p=0.0038). The PP OSA group spent 43% of total recording time in the supine position. Conclusions: The prevalence of PP OSA patients studied with RP is similar to the one described by sleep laboratories. They have lower BMI, present mostly mild OSA with less desaturation, and are less likely to receive CPAP therapy. PMID- 29796195 TI - Efficiency of the Ocluch(c)MAD in the treatment of patients with OSAS and its association with craniofacial morphology. AB - Objective: This study uses polysomnography and the Epworth sleepiness scale to assess the efficiency of the Ocluch(c)MAD in patients with Obstructive sleep apnea-hypopnea syndrome (OSAS), on overall respiratory disturbance indices (RDI), supine respiratory disturbance index (SRDI), minimum oxygen saturation, microarousals, CT90 (or ID90), sleep efficacy and snoring. These data are associated with skeletal class and facial biotype in order to establish predictive parameters for its effectiveness according to craniofacial morphology. Methods: 22 adult patients (between 38 and 60 years of age) of both sexes (7 women, 15 men) diagnosed with OSAS in the Hospital de Carabineros de Chile (HOSCAR) Neurology Unit were recruited and given the Ocluch(c) MAD in the hospital's dental clinic, for its use during a three-month period. Patients were assess at the beginning and in the end of this period. Results: 87.5% of patients with mild OSAS achieved the success criterion and normalization; 71.5% of patients with moderate OSAS achieved the success criterion and 33.3% achieved normalization; 85.7% of patients with severe OSAS achieved the success criterion and 57.1% achieved normalization. All class I and mesofacial patients achieved normalization, but class II patients had the greatest proportional improvement. Conclusions: The Ocluch MAD is an efficient low-cost alternative that should be considered among the therapeutic arsenal for a multidisciplinary approach to treating this disease. PMID- 29796196 TI - Sleep respiratory disturbances during the ascent to Mount Aconcagua. AB - Introduction: Mountaineers exposed to hypobaric hypoxia (HH) show high-altitude periodic breathing (PB). Objective: To analyze high-altitude PB during the ascent of Mount Aconcagua (Argentina). Materials and Methods: Descriptive study in healthy volunteers using respiratory polygraphy (RP) at different altitudes. Results: We studied 8 andinist, mean age: 36 years old (25-51), body mass index (BMI) of 23.6 (20.9-28.7) and 22.77 (20.9-27.7) upon return, p<0.01. RP without PB showed a lower Oxygen Desaturation Index (ODI) and a lower Apnea-Hypopnea Index (AHI); 5.43 (0 - 20) versus 45.95 (2-122) p<0.001 and 3.9 (0-15.5) versus 44.35 (4-115) p<0.001. AHI increased with altitude at the expense of central apneas and hypopneas: p<0.05. Conclusion: High-altitude PB is frequent above 2,581m.a.s.l. And it is characterized by short cycles. None of the mountaineers showed PB at baseline; however, high-altitude PB occurred in all subjects above 4,900 m.a.s.l. PMID- 29796197 TI - A rare differential diagnosis of excessive daytime sleepiness - Artery of Percheron territory infarct. AB - Stroke is an example of neurological diseases that can commonly drives Excessive Daytime Sleepiness (EDS). Extensive strokes with brain edema can leave a brain herniation and coma. Other causes of EDS after stroke are strategic lesions at Thalamus and brainstein. A 56-year-old man, right handed, with hypertension and hypercholesterolemia was admitted at Emergency Room due to 5 days onset of EDS, memory impairment, and left-sided weakness. A brain magnetic resonance imaging showed paramedian thalamic hyperintensity with rostral midbrain hyperintensity extending along the pial surface of the interpeduncular fossa. The artery of Percheron (AP) is an unusual anatomical variation that originates from the posterior cerebral artery and irrigates the paramedian regions of the thalamus and part of the midbrain. It is important the clinical suspicions with detailed drowsy patients history. Awareness of the clinical and neuroimaging features of this stroke syndrome is essential for timely diagnosis and appropriate management. PMID- 29796198 TI - Reproducibility and predictors of the apnea hypopnea index across multiple nights. AB - Background: Attended polysomnography (PSG) is the standard diagnostic test for sleep apnea (SA). However, due to internight variability in SA, a single night PSG may not accurately reflect the true severity of SA. Although internight variability is a well-known phenomenon, its root causes have not been fully elucidated. The objective of this study was to determine factors associated with internight variability in the apnea-hypopnea index (AHI) and its magnitude in the home environment. Methods: Each participant had a full overnight PSG simultaneous with a validated portable sleep apnea monitoring device (BresoDx(r)) followed by two overnight home tests using the portable monitor only. Patients were stratified into those with variable AHI and consistent AHI (AHI difference >=10 or <10 between any 2 nights, respectively). Demographics, sleepiness, sleep test variable, and supine-predominant SA (supine-SA) were examined for any association with variable AHI. Results: Forty patients completed the protocol. The correlation between PSG and simultaneous BresoDx derived AHIs was 93.4%. Inter class correlation between the three nights' AHIs was 89.2%. Over two-thirds (67.5%) of patients had consistent AHIs across the three nights while 32.5% had variable AHI. AHI variability was significantly associated with supine-SA (p=0.0014) and correlated with first night's AHI (r=0.664, p<0.001). None of the other variable, including BMI, sleepiness, gender, or test duration were associated with internight variability. Conclusion: Although portable monitoring was highly reproducible over three nights in the majority of participants, one third had a variable AHI. Supine-SA and high AHI on the first night were predictors of high internight variability. PMID- 29796199 TI - Narcolepsy with cataplexy and hyperthyroidism sudden appeared after H1N1 vaccination. AB - Narcolepsy type 1 (NT1) is a chronic sleep disorder, characterized by excessive daytime sleepiness, cataplexy and fragmented nocturnal sleep. It is caused by a hypocretin deficiency due to a significant reduction of the neurons producing it. In the last years, it has been postulated that an autoimmune mechanism would be responsible for the destruction of these neurons in those genetically predisposed patients. The increased incidence of narcolepsy after the pandemic H1N1 influenza vaccination campaign in 2009-2010 is known. We present below the case of an adult patient who, 10 days after receiving H1N1 vaccination, suffers a traffic accident after falling asleep. Subsequent studies revealed hyperthyroidism due to Graves disease. In spite of the treatment, the patient persisted with daily and disabling daytime sleepiness, sleep attacks and episodes of generalized muscle atony with preservation of consciousness. A nocturnal polysomnography and multiple sleep latency test (MSLT) were performed with a diagnosis of NT1. The particularity of this case is the presentation of 2 autoimmune diseases triggered by an H1N1 vaccine without adjuvant, so far there is only evidence of NT1 associated with vaccines with adjuvant and viral infection. The association of both entities has made us reflect on the autoimmune mechanism, reinforcing the theory of its role in the onset of the disease. PMID- 29796200 TI - Development of the athlete sleep behavior questionnaire: A tool for identifying maladaptive sleep practices in elite athletes. AB - Introduction: Existing sleep questionnaires to assess sleep behaviors may not be sensitive in determining the unique sleep challenges faced by elite athletes. The purpose of the current study was to develop and validate the Athlete Sleep Behavior Questionnaire (ASBQ) to be used as a practical tool for support staff working with elite athletes. Methods: 564 participants (242 athletes, 322 non athletes) completed the 18-item ASBQ and three previously validated questionnaires; the Sleep Hygiene Index (SHI), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). A cohort of the studied population performed the ASBQ twice in one week to assess test-retest reliability, and also performed sleep monitoring via wrist-actigraphy. Results: Comparison of the ASBQ with existing sleep questionnaires resulted in moderate to large correlations (r=0.32 - 0.69). There was a significant difference between athletes and non athletes for the ASBQ global score (44+/-6 vs. 41+/-6, respectively, p<0.01) and for the PSQI, but not for the SHI or the ESS. The reliability of the ASBQ was acceptable (ICC=0.87) when re-tested within 7 days. There was a moderate relationship between ASBQ and total sleep time (r=-0.42). Conclusion: The ASBQ is a valid and reliable tool that can differentiate the sleep practices between athletes and non-athletes, and offers a practical instrument for practitioners and/or researchers wanting to evaluate the sleep behaviors of elite athletes. The ASBQ may provide information on areas where improvements to individual athletes' sleep habits could be made. PMID- 29796201 TI - Apnea-hypopnea index in sleep studies and the risk of over-simplification. AB - According to recent reports, sleep disorders affect 30% of the adult population and 5-10% of children. Obstructive Sleep Apnea Hypopnea Syndrome (OSA) has a considerable epidemiological impact and demand for consultation is growing in our community. Therefore, it is necessary to know the principles of interpretation of diagnostic methods. A suspicion of OSA requires confirmation. According to the guidelines of the Argentine Association of Respiratory Medicine, polysomnography (PSG) is the gold standard for OSA diagnosis, while home sleep testing (HST) can be accepted as a comparatively effective method depending on the clinical situation of the patient. This article questions the use of AHI (apnea-hypopnea index) as the only measurement needed to diagnose OSA and assess its severity. In fact, it is surprising that, despite the large mass of data analyzed during sleep studies, current practices only focus on AHI. More than four decades have passed since OSA was first described. Our tendency to oversimplify complex conditions may prevent us from gaining a deeper and more thorough understanding of OSA. The development and validation of OSA severity scoring systems based on multiple parameters is still a pending issue. PMID- 29796203 TI - Otorhinolaryngology articles in the Malaysian Family Physician. PMID- 29796202 TI - Acute response to 7-day therapy with CPAP in patients with moderate to severe obstructive sleep apnea and cardiac arrhytmia. AB - Introduction: Obstructive Sleep Apnea (OSA) has been associated with an elevated risk of cardiac arrhythmia. Continuous positive airway pressure (CPAP) is the selected treatment for moderate to severe OSA and could improve arrhythmias in the long term. However, the acute effect of CPAP has not been studied in detail. Methods: We conducted a prospective study with 25 patients with moderate to severe OSA diagnosed by home respiratory polygraphy (RP) and arrhythmia and/or pauses in 24-hour Holter ECG. We analyzed inflammatory parameters and the rate of arrhythmias/pauses after 7 days of auto-adjusting CPAP. Results: 92.5% of the patients were men with a mean age of 61.7+/-1.9 years. Body mass index (BMI) was 59.5+/-2.2 kg/m2, with a mean apnea hypopnea index (AHI) of 37.7+/-3.8 events/hour (ev/h), and a residual AHI (AHIr) of 5.3+/-0.53 ev/h. After short treatment with CPAP we observed a tendency to improvement in both the severity and number of ventricular extrasystoles (VE) (1595.0+/-850.3 vs. 926.4+/-434.5 respectively), pauses and the inflammatory parameters (CRP 3.9+/-3.1 vs. 1.7+/ 1.2, glycemia 131.4+/-11.6 vs. 121.9+/-9.8, HOMA 24.4+/-3.1 vs. 21.7+/-2.8, insulin 7.6+/-1.4 vs. 7.2+/-1.2 (p>0.5). Conclusion: We didn't find significant changes in pauses, VE and inflammatory parameters with CPAP short therapy in CPAP naive patients recently diagnosed with OSA. PMID- 29796204 TI - Hypertension and its association with Anthropometric indices among students in a public university. AB - Introduction: The present study aimed to determine the prevalence of hypertension and its association with nutritional status (body mass index, body fat percentage, and visceral fat) among students in a public university in Sarawak, Malaysia. Methods: This was a cross-sectional study among undergraduate students aged 18 years old and above. Anthropometric measurements, such as weight, height, body composition, and blood pressure measurements, were collected. Hypertension was defined as equal or more than 140/90 mmHg. Statistical analyses were done using IBM SPSS version 20. Results: A total of 354 respondents participated in the study. Mean age for the respondents was 21 years (SD 1.18 years). About 40% of the respondents were overweight or obese. Prevalence of hypertension was 8.2%. Mean systolic blood pressure was 119.1mmHg (SD14.36mmHg), and the mean diastolic blood pressure was 72.6mmHg (SD 9.73mmHg). There is a significant association between male gender (odds ratio =3.519, 95% CI is 1.886-6.566), body fat percentage (odds ratio = 1.944, 95% CI is 1.050-3.601), visceral fat (odds ratio = 2.830, 95% CI is 1.346-5.951), and family history of hypertension (odds ratio= 2.366, 95% CI is 1.334-4.194) and hypertension. Conclusion: The prevalence of hypertension was less than 10% and is associated with male gender, body composition, and family history of hypertension. PMID- 29796205 TI - Non-Adherence to recommended Pap smear screening guidelines and its associated factors among women attending health clinic in Malaysia. AB - Introduction: Cervical cancer ranks as the second most frequent cancer among women in Malaysia. Although a cervical screening program has been introduced since 1960s and is provided free of charge in all government health facilities, the coverage and adherence rate to recommendation among Malaysian women remains low. Objectives: To determine the proportion of non-adherence to Pap smear screening guidelines and its associated factors among women attending a health clinic in Malaysia. Method: A cross sectional study involving 316 women aged 20 to 65 years who had undergone a Pap smear. Universal sampling method was applied to select participants among women who attended the selected health clinic from January 2013 to May 2013. A self-administered questionnaire was used to obtain the socio-demographic characteristics, socio-health data and perceptions about cervical cancer and Pap smear screening. The data was analysed using descriptive statistics and multiple logistic regression. Result: The proportion of non adherence to Pap smear screening was 90.5%. Age, marital status, duration of marriage, education level, employment, household income and number of children were not significantly associated with non-adherence. Perceived severity, perceived susceptibility, perceived benefit, perceived barrier and cues to action did not show significant association with non-adherence to Pap smear screening. Conclusion: Non-adherence to Pap smear screening was high among Malaysian women. Measures should be taken to increase Pap smear screening coverage in our country. Other factors beyond Health Belief Model that influence Pap smear screening practice among Malaysian women should be explored. PMID- 29796206 TI - The views and experiences of Malaysian primary care doctors in managing patients with chronic low back pain: a qualitative study. AB - Background: Chronic low back pain (CLBP) is a common and often difficult to treat condition in the primary care setting. Research involving in-depth exploration on the views and experiences faced by primary care doctors in managing patients with CLBP in Malaysia is limited. Objective: To explore the primary care practitioners' views and experiences in managing patients with CLBP. Study design: A qualitative approach was employed using focus group discussions (FGD) at an academic primary care clinic in Kuala Lumpur, Malaysia. Twenty-three primary care doctors were purposively selected. Data were collected through audio recorded interviews, which were transcribed verbatim and checked for accuracy. Data saturation was reached by the third FGD. An additional FGD was included to ensure completeness. A thematic approach using the one sheet of paper (OSOP) method was used to analyse the data. Results: Participants view managing patients with CLBP as challenging. This is mainly due to the difficulty in balancing the doctors' expectations with the patients' perceived expectations during consultation. Barriers identified include lack of awareness and conflicting views regarding the usefulness of the local clinical practice guideline (CPG) in clinical practice. Other barriers include time constraints and perceived lack of support from multidisciplinary teams in managing these patients. Conclusion: Managing patients with CLBP is still a challenge for Malaysian primary care doctors. Any intervention should target identified barriers to improve the management of patients with CLBP. PMID- 29796207 TI - Management of rhinosinusitis in adults in primary care. AB - Rhinosinusitis is a common health problem encountered in primary care. It is due to mucosal inflammation of the nose and paranasal sinuses. Less than 2% of the cases are associated with bacterial infections. Diagnosis is based on clinical symptoms and supported by nasal endoscopy and imaging studies. Intranasal corticosteroids and normal saline irrigation are important treatments. Antibiotics are seldom indicated. PMID- 29796208 TI - A food bolus obstructing the oesophagus in a patient with infantile cerebral palsy. AB - Introduction: A foreign body (FB) in the upper aerodigestive tract is a fairly common encounter. Fish bones are the commonest FB seen in adults. The commonest presentation is odynophagia. Usually, the patient will point at the level of FB on the neck to indicate the location. Methods: Clinical report. Results: This case report describes a large FB in an adult with underlying infantile cerebral palsy. Besides dysphagia, it was associated with drooling of saliva and pain in the throat region. Conclusion: FB ingestion with complete obstruction of the oesophagus is an emergency. It may cause total dysphagia as the passage of food is completely blocked. PMID- 29796209 TI - Lemierre's syndrome: A persistent unusual neck pain and swelling. AB - Lemierre's syndrome is a systemic complication commonly caused by oropharyngeal infection by Fusobacterium species, which manifests itself as an internal jugular vein thrombosis formation. It is a rare occurrence nowadays with the availability of broad spectrum antibiotics for treatment. Most cases in the literature presented with a life-threatening condition. We are reporting a case of Lemierre's syndrome that presented with persistent neck pain and swelling, initially diagnosed as cervical lymphadenitis. PMID- 29796210 TI - Bilateral peritonsillar abscess: A rare emergency. AB - Peritonsillar abscess, or quinsy, is a rare complication of acute tonsillitis. It usually presents with odynophagia, trismus, and muffled voice, reflecting the space-occupying lesion in the oral cavity. Examination reveals a unilateral swelling on either side of the soft palate, which drains thick pus after an incision is made. It is regarded as an emergency as an upper airway obstruction can develop. Bilateral peritonsillar abscess is a rare presentation and results in catastrophic sequelae. We present a case of bilateral peritonsillar abscess that was initially referred by a primary care centre facing a dilemma in diagnosis. Prompt diagnosis and fast drainage are warranted to avoid unwanted morbidity, and, also, mortality. PMID- 29796211 TI - Glomus tympanicum. AB - Glomus tympanicum is a tumour classified under the group glomus tumours, and is also known as paragangliomas. It is thought to commonly occur in women in the fifth to sixth decades of life. Here, we report a case of a 77-year-old lady with multiple co-morbids and a diagnosis of glomus tympanicum presenting to us. Her symptoms included pulsatile tinnitus, and reduced hearing, and the management of the case was done with consideration for her underlying multiple co-morbidities. This paper also describes the best modality of treatment for this patient with regard to her background history. The treatment goal was to improve her quality of life and control the disease. PMID- 29796212 TI - Hypopigmented patches in an 8-year-old boy. PMID- 29796213 TI - The man with sweaty palms and soles. PMID- 29796214 TI - A child with coated tonsils. PMID- 29796215 TI - Single rare central lesion with triple common aerodigestive symptoms. PMID- 29796217 TI - Trans-chalcone enhances insulin sensitivity through the miR-34a/SIRT1 pathway. AB - Objectives: Trans-chalcone as the parent member of the chalcone series reduces circulating levels of insulin and glucose. However, the cellular mechanism of these effects is poorly understood. Sirtuin 1 (SIRT1) as a direct target of miR 34a controls homeostasis of glucose, and also improves insulin sensitivity. Therefore, the present study for the first time investigated the influence of trans-chalcone on the miR-34a/SIRT1 pathway as a possible mechanism for its hypoglycemic and hypoinsulinemic effects. Materials and Methods: In this study, thirty male rats were randomly divided into three groups (n=10): solvent control (NS), oral administration of trans-chalcone for 2 (N2T) and 6 weeks (N6T) groups. Then, hepatic levels of miR-34a and SIRT1 were measured through the qRT-PCR method. Results: Trans-chalcone reduced food intake, body weight gain, and serum glucose as well as insulin levels. Also, this chalcone inhibited hepatic miR-34a expression and significantly elevated SIRT1 mRNA level. Conclusion: Trans chalcone as an insulin-sensitizing chalcone partly acts through the miR-34a/SIRT1 pathway. PMID- 29796216 TI - Medicinal herbs in the treatment of neuropathic pain: a review. AB - Chronic neuropathic pain is a common significant and debilitating problem that presents a major challenge to health-care. Despite the large number of available drugs, there are no curative conventional treatments for neuropathic pain. Nowadays, more attention has been focused on the herbal formulation in the field of drug discovery. Therefore, we performed an extensive review about herbal drugs and plants that exhibited protective effects on neuropathic pain. In this review, the beneficial effects of each plant in different neuropathic pain model, either in animals or in patients are reported. Moreover, the possible involved mechanisms for the protective effects are discussed. The more common plants which are used for the treatment of neuropathic pain are included as: Acorus calamus, Artemisia dracunculus, Butea monosperma, Citrullus colocynthis, Curcuma longa, Crocus sativus, Elaeagnus angustifolia, Ginkgo biloba, Mitragyna speciosa, Momordica charantia, Nigella sativa, Ocimum sanctum, Phyllanthus amarus, Pterodon pubescens Benth, Rubia cordifolia and Salvia officinalis. Furthermore, the most pathways which are known to be involved in pain relief by means of herbal remedies are anti-oxidant activity, anti-inflammatory, anti-apoptotic, neuroprotective and calcium inhibitory actions. In conclusion, this review suggests that some herbal plants can be suitable candidates for the treatment of neuropathic pain. PMID- 29796218 TI - 5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production. AB - Objectives: P2X4R is expressed in immunocyte and lung tissues. It has been a focus in inflammatory responses recently. This study investigated whether blockage of P2X4R attenuates allergic inflammation by modulating T cell response in ovalbumin-sensitized mice. Materials and Methods: Ovalbumin was used to sensitize and challenge for a mouse model. Intranasal application of 5-BDBD, P2X4R antagonist, were performed 3 hr before each airway allergen challenge. The lung was evaluated for P2X4R by real-time PCR and immunofluorescence. Th1/Th2 cytokines in bronchoalveolar lavage fluid were measured by ELISA. T-bet, Gata-3, and p-p38 MAPK were measured by Western blot or real-time PCR. Results: P2X4R was overexpressed in the lung after allergen challenge compared with the control group. Blockage of P2X4R decreased inflammation in the lung, IL-4 expression was reduced as well as IL-5; IFN-gamma expression was elevated in BALF in ovalbumin sensitized mice. Moreover, blockage of P2X4R inhibited ovalbumin-induced increased Gata-3 level and decreased T-bet level. Conclusion: These findings suggest that 5-BDBD ameliorates an ovalbumin-induced asthmatic attack by the downregulation of cytokines related to the Th2 cell. PMID- 29796219 TI - Deep brain stimulation in a rat model of post-traumatic stress disorder modifies forebrain neuronal activity and serum corticosterone. AB - Objectives: Post-traumatic stress disorder (PTSD), one of the most devastating kinds of anxiety disorders, is the consequence of a traumatic event followed by intense fear. In rats with contextual fear conditioning (CFC), a model of PTSD caused by CFC (electrical foot shock chamber), deep brain stimulation (DBS) alleviates CFC abnormalities. Materials and Methods: Forty Male Wistar rats (220 250 g) were divided into 5 groups (n=8) and underwent stereotactic surgery to implant electrodes in the right basolateral nucleus of the amygdala (BLn). After 7 days, some animals received a foot shock, followed by another 7-day treatment schedule (DBS treatment). Next, freezing behavior was measured as a predicted response in the absence of the foot shock (re-exposure time). Blood serum corticosterone levels and amygdala c-Fos protein expression were assessed using Enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Furthermore, freezing behaviors by re-exposure time test and general anxiety by elevated plus-maze (EPM) were evaluated. Results: PTSD decreased serum corticosterone levels and increased both amygdala c-Fos expression and freezing behaviors. Therefore, DBS treatment significantly (P<0.001) enhanced serum corticosterone levels and could significantly (P<0.001) reduce both c-Fos protein expression and freezing behaviors' duration. However, DBS treatment has no effect on the general anxiety in PTSD rats. Conclusion: We argue that these outcomes might demonstrate the mechanism of DBS treatment, a complete therapeutic strategy, in PTSD patients. PMID- 29796220 TI - Evaluation of nicotinic receptor of pedunculopontine tegmental nucleus in central cardiovascular regulation in anesthetized rat. AB - Objectives: Cholinergic neurons are important neurons in the Pedunculopontine tegmental nucleus (PPT). In this study, nicotinic receptor of the PPT in central cardiovascular regulation in the anesthetized rat was evaluated. Materials and Methods: Saline, acetylcholine (Ach; doses: 90 and 150 nmol), hexamethonium (Hexa; doses: 100 and 300 nmol) and higher doses of Hexa (300 nmol) + Ach (150 nmol) microinjected into the PPT. The femoral artery was cannulated and cardiovascular responses were continuously recorded by a power lab system. After injection of drugs, peak changes of mean arterial pressure (?MAP), systolic blood pressure (?SBP) and heart rate (?HR) calculated and compared with saline group. Results: The ?SBP and ?MAP significantly decreased by two doses of Ach (P<0.05 to P<0.001) but ?HR did not change. Two doses 100 (P<0.05) and 300 nmol (P<0.01) of Hexa significantly increased ?HR but did not alter the ?MAP or ?SBP. Co-injection of Hexa + Ach significantly strengthened the ?HR induced by Hexa alone (P<0.01) but did not affect ?MAP or ?SBP. Conclusion: These results indicate that nicotinic receptor of the PPT has an inhibitory effect on ?HR with no significant effect on ?MAP or ?SBP. PMID- 29796222 TI - Development of monoclonal antibodies against axenic amastigotes of Leishmania infantum strain in Iran: implication for diagnosis of Kala-azar. AB - Objectives: Leishmaniasis is endemic in 88 countries. Amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection. Monoclonal antibodies are key reagents used in the diagnosis of infectious and non-infectious diseases. The aim of this study was to produce monoclonal antibodies against axenic amastigotes of the Leishmaniainfantum strain in Iran. Materials and Methods: First, standard strains were cultured and axenic amastigote antigens of L. infantum were obtained. Since then, BALB/c smice were immunized and antibody titers were determined. For hybridoma cell formation, lymphocytes isolated from spleen of immunized mice and myeloma cells were fused at a ratio of 10 to 1 in the presence of polyethylene glycol, followed by limiting dilution for the isolation of monoclones. Subsequently, antibody isotypes were determined by using the isotyping kit. The best clone was injected intraperitoneally to pristane-primed mice for large scale production of monoclonal antibodies. The specificity of antibody was determined with Western blotting. Results: Approximately 25 positive monoclones were obtained, of which four hybrids producing anti-amastigotes L. infantum monoclonal antibodies with high optical density (OD), selected and designated as 8D2 FVI6, 8D2 FVI3, 6G2 FV4 and 6G2 FV3. Results from isotype determination showed the IgG2b sub-class in 6G2FV2 and 8D2FVI6 monoclones. Conclusion: This study produced monoclonal antibody against amastigotes of Iranian strain of L. infantum for the first time. These antibodies have reactivity against Iranian strain of L. infantum and can be used in the diagnosis of Kala-azar. PMID- 29796221 TI - Can crocin play a preventive role in Wistar rats with carbon tetrachloride induced nephrotoxicity? AB - Objectives: To investigate protective role of crocin by attempting to create nephrotoxicity with carbon tetrachloride. Materials and Methods: Ethics committee approval was obtained and 50 male Wistar rats were randomly divided into 5 groups that included 10 rats each: Control, Corn oil, Crocin, Carbon tetrachloride (CCl4), and Crocin + Carbon tetrachloride. Following the experiments, the rats were decapitated under anesthesia and incised kidney tissues were subjected to biochemical and histological examinations. Results: In the CCl4 administered group, MDA, TOS, Bun, and creatinine levels increased, GSH, SOD, CAT, and TAS levels decreased (P<=0.05), glomerular collapse in kidney sections, narrowing and local occlusion in Bowman's space in certain glomeruli, inflammatory cell infiltration and congestion were observed when compared to all other groups. There was a significant decrease in increased MDA, TOS, Bun, and creatinine levels, and a significant increase in decreased GSH, SOD, CAT, and TAS levels in CCl4 + crocin administered group compared to the CCl4 group (P<=0.05), local minimal glomerular damage, tubular damage, inflammatory infiltration, and vascular collagen symptoms were observed in kidney sections, however significant improvement was observed in damage findings when compared to the CCl4 group. Conclusion: At this dose and time interval, against a highly toxic chemical such as CCl4, crocin was able to suppress oxidative stress by playing a protective role in the kidney tissue. PMID- 29796223 TI - The effect of intracerebroventricular injection of CGRP on pain behavioral responses and monoamines concentrations in the periaqueductal gray area in rat. AB - Objectives: Calcitonin gene related peptide (CGRP) receptors are widely distributed in the central nervous system. The aim of this study was to investigate the effects of intracerebroventricular (ICV) injection of CGRP on pain behavioral responses and on levels of monoamines in the periaqueductal gray area (PAG) during the formalin test in rats. Materials and Methods: Twenty-four male rats were studied in four groups (n=6). CGRP was injected into the left cerebral ventricle (1.5 nmol, 5 ul). After 20 min, formalin (2.5%) was subcutaneously injected into the right hind paw. Behavior nociceptive score was recorded up to 60 min. During the formalin test, the PAG was subjected to microdialysis and levels of norepinephrine, 3-methoxy-4-hydroxyphenyl-glycol (HMPG), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin and 5 hydroxyindole-acetic acid (HIAA) were measured by HPLC. Results: ICV injection of CGRP lead to a significant pain reduction in acute, middle and chronic phases of the formalin test. Dialysate concentrations of norepinephrine, HMPG, dopamine, DOPAC, serotonin and HIAA in the PGA area showed an increase in acute phase, middle phase and beginning of the chronic phase of the formalin test. Conclusion: CGRP significantly reduced pain by increased concentrations of monoamines and their metabolites in dialysates from PAG when injected ICV to rats. PMID- 29796224 TI - Association between biofilm production, adhesion genes and drugs resistance in different SCCmec types of methicillin resistant Staphylococcus aureus strains isolated from several major hospitals of Iran. AB - Objectives: The ability of bacteria to produce biofilm and adhesion makes them more resistant to antibiotics. The current study aims to evaluate the biofilm formation by Staphylococcus aureus and to determine the prevalence of adhesion genes, also their correlation with drug resistance. Materials and Methods: A total of 96 MRSA were collected from hospitals of Iran's western provinces during 2012 to 2013. The presence of ica A, B, C, D, clfA, cna, fnbA, mecA genes were determined by PCR technique. Biofilm formation was studied by microtiter plate assay, the clonal relations of the strains were examined by SCCmec and Spa typing. Results: The results demonstrated that 96 % of isolates were biofilm producers. The distributions of biofilm formation between isolates were 4.2%, 54.2%, 35.4% as high, moderate and weak, respectivelly. The highest biofilm production was observed from blood culture isolates. All virulent genes icaA,B, C, D, clfA, cna, fnbA were observed in moderate and weak biofilm formation isolates. Among high biofilm formation isolates, icaB and cna genes were not seen. Statistical analysis showed that there was a significant correlation between ica, fnbA and the biofilm production, but there was not a significant correlation between the type of samples and drug resistance, spa type and SCCmec type with biofilm production (P>0.05). Frequency of All virulent genes in type III SCCmec was higher than other types. Conclusion: The majority of MRSA isolates were biofilm producers and blood isolates ranked as the great biofilm producer. In these isolates ica D and fnbA genes are correlated with biofilm production. PMID- 29796225 TI - The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. AB - Objectives: 5-fluorouracil-induced (5-FU), an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity. Materials and Methods: Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringin+5-FU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken. Results: It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringin+5-FU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringin+5-FU groups. Conclusion: Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage. PMID- 29796226 TI - DNA protection, antioxidant and xanthine oxidase inhibition activities of polyphenol-enriched fraction of Berberis integerrima Bunge fruits. AB - Objectives: The aim of this study was to prepare fraction and determine the biological activities of the polyphenol-enriched fraction of Berberis integerrima Bunge fruits. Materials and Methods: In this assay fraction was extracted by column chromatography, using Amberlite column as the stationary phase. Phenol and flavonoids in the extract and fraction were analyzed by high performance liquid chromatography (HPLC). DNA protection ability, antioxidant and xanthine oxidase inhibition capacities of this fraction were also examined. Results: Phenol and flavonoid content measurement and HPLC analyses of this fraction confirmed that phenol and flavonoids were increased in fraction in comparison to extract (before using Amberlite column). In antioxidant measurement assay, the trolox equivalent values were 1.05+/- 0.04 and 0.8+/-0.11 in oxygen radical absorbance capacity (ORAC) and the EC50 values for cellular antioxidant activity were 55.51+/-0.21 and 95.67+/-0.13 ug/ml for quercetin and the fraction, respectively. The xanthine oxidase inhibition percentages were 97.6+/-0.003 and 90.2 6+/-0.003 in 100 ug/ml concentration of fraction and vitamin C respectively. Comet assay analysis showed that this fraction protects human lymphocytes against H2O2-induced DNA damages at 12.5 to 100 ug/ml concentrations. Conclusion: This study suggests that Amberlite column as the stationary phase help to improve phenolic compound in separating fractions. The results showed that B. integerrima fruits are rich in phenolic compounds and they are potent antioxidants with protective effects on oxidative damages. They might be used as functional ingredients in food and supplements. PMID- 29796227 TI - Effect of maternal fluoxetine exposure on lung, heart, and kidney development in rat neonates. AB - Objectives: Depression during pregnancy negatively affects fetal development. Fluoxetine as a selective serotonin reuptake inhibitor (SSRIs) is used for treatment of gestational depression. This study is trying to determine the effects of fluoxetine on the renal, heart and lung development. Materials and Methods: Fifteen pregnant rats were treated with fluoxetine at 7 mg/kg from days 0 to 21 of gestation. Immediately after born, heart and kidney samples were evaluated for genes expression and histological assessment. Lung sample were fixed for immunohistochemical study. Results: The gene expression of BMP7 and WNT4 were reduced in the kidney of fluoxetine-treated group (P-value<0.05), but in the heart of both groups no significant difference was found in gene expression (P-value>0.05). Histological assessment showed that the glomeruli of the kidneys in treated group are more primordial compared to control. There was a developmental deficiency in Bowman's capsule, and the capsular space was not clear. The arrangements of the filaments, the position of the nucleus and cells morphology were normal in the hearts of both groups. Immunohistochemical analysis demonstrated that in the fluoxetine-exposed group HoxB5 is more expressed in the mesenchymal cells, but in the control group the expression is limited to alveolar cells. Conclusion: According to developmental changes in kidney, heart and lung, fluoxetine affects neonatal growth during pregnancy, which may lead to delay of some organs growth. So, it is essential to survey the roles of antidepressant drugs on fatal and neonatal development during pregnancy. PMID- 29796228 TI - Effects of salidroside on rat CYP enzymes by a cocktail of probe drugs. AB - Objectives: In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats, in which a specific probe drug was used for each enzyme. Materials and Methods: After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was 2.0 mg/kg for phenacetin (CYP1A2 activity), 4.0 mg/kg for bupropion (CYP2B6 activity), 2.0 mg/kg for losartan (CYP2C9 activity), 8.0 mg/kg for metoprolol (CYP2D6 activity) and 1.0 mg/kg for midazolam (CYP3A4 activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats' blood, which were collected at different corresponding times. Results: Our data showed that salidroside exhibited an inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A4 activities by changing the main pharmacokinetic parameters (t1/2, CL/F, Cmax and AUC(0-infinity)) of the four probe drugs in rats. However, no significant changes in CYP2D6 activity were observed. Conclusion: In a word, the results displayed that salidroside could induce the activities of CYP1A2, CYP2B6, CYP2C9 and CYP3A4, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic. PMID- 29796229 TI - Inhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics. AB - Objectives: Various studies have been conducted to reduce the metastatic behavior of cancerous cells. In this regard, ectopic expression of anti-metastatic microRNAs by miR-mimic and miR-restoration-based therapies could bring new insights to the field. In the present study, the consequences of co-transfecting breast cancer cell lines with miR-193b and miR-31 were investigated via invasion and migration assays. Materials and Methods: Double stranded oligonucleotide of mature miR-193b-3p and miR-31-5p were cloned into pcDNA 6.2gw/EmGFP plasmid. The resulting plasmids were used for transfection. Real time-PCR was performed to assess the expression of miR-193b and miR-31 as well as Ras homolog gene family member A (RhoA) and urokinase-type plasminogen activator (uPA) as miR targets. Scratch, Transwell migration and Matrigel invasion assays were carried out to assess the extent of migration and invasion of cell lines. Results: The most significant increase in expression of miRs belonged to the single transfection of mimic-miRs in MDA-MB231. Although the co-transfection was not as successful as single transfection in miR expression, it was significantly more effective in inhibition of the cells invasive potential. Conclusion: Although the miR restoration therapy based on co-transfection of two miRs could be less effective in expression of each miRNA, the resulting decrease in metastatic behavior of the cells is more significant due to collective effect of co-transfection to decrease target gene expression. Our results revealed that employing this sort of combinatorial strategies could lead to more efficient reduction in metastatic behavior. It seems that using this strategy would bring about more successful therapeutic outcomes. PMID- 29796230 TI - The effects of vitamin B12 on the brain damages caused by methamphetamine in mice. AB - Objectives: Methamphetamine (METH) is a powerful stimulant drug that directly affects the brain and induces neurological deficits. B12 is a water-soluble vitamin (vit) that is reported to attenuate neuronal degeneration. The goal of the present study is to investigate the effect of vitamin B12 on METH's neurodegenerative changes. Materials and Methods: Two groups of 6 animals received METH (10 mg/kg, interaperitoneally (IP)) four times with a 2 hr interval. Thirty mins before METH administration, vit B12 (1 mg/kg) or normal saline were injected IP. Animals were sacrificed 3 days after the last administration. Caspase proteins levels were measured by Western blotting. Also, samples were examined by TUNEL assay to detect the presence of DNA fragmentation. Reduced glutathione (GSH) was also determined by the Ellman method. Results: The pathological findings showed that vit B12 attenuates the gliosis induced by METH. Vit B12 administration also significantly decreased the apoptotic index in the striatum and the cerebral cortex (P<0.001). It also reduced caspase markers compared to the control (P<0.01 and P<0.001, respectively). Interestingly, co administration of METH and Vit B12 elevates the levels of GSH in both regions of the brain and returned it to normal levels compared to the METH group. Conclusion: The current study suggests that parenteral vit B12 at safe doses may be a promising treatment for METH-induced brain damage via inhibition of neuron apoptosis and increasing the reduced GSH level. Research focusing on the mechanisms involved in the protective responses of vit B12 can be helpful in providing a novel therapeutic agent against METH-induced neurotoxicity. PMID- 29796231 TI - Linear Phase Sharp Transition BPF to Detect Noninvasive Maternal and Fetal Heart Rate. AB - Fetal heart rate (FHR) detection can be monitored using either direct fetal scalp electrode recording (invasive) or by indirect noninvasive technique. Weeks before delivery, the invasive method poses a risk factor to the fetus, while the latter provides accurate fetal ECG (FECG) information which can help diagnose fetal's well-being. Our technique employs variable order linear phase sharp transition (LPST) FIR band-pass filter which shows improved stopband attenuation at higher filter orders. The fetal frequency fiduciary edges form the band edges of the filter characterized by varying amounts of overlap of maternal ECG (MECG) spectrum. The one with the minimum maternal spectrum overlap was found to be optimum with no power line interference and maximum fetal heart beats being detected. The improved filtering is reflected in the enhancement of the performance of the fetal QRS detector (FQRS). The improvement has also occurred in fetal heart rate obtained using our algorithm which is in close agreement with the true reference (i.e., invasive fetal scalp ECG). The performance parameters of the FQRS detector such as sensitivity (Se), positive predictive value (PPV), and accuracy (F1) were found to improve even for lower filter order. The same technique was extended to evaluate maternal QRS detector (MQRS) and found to yield satisfactory maternal heart rate (MHR) results. PMID- 29796232 TI - Earable RCC: Development of an Earphone-Type Reliable Chewing-Count Measurement Device. AB - Gastric cancer patients having undergone gastrectomy are at a high risk of becoming malnourished owing to decreased gastric function. To prevent malnutrition, patients need to thoroughly chew a mouthful of food at least 30 times. For these gastrectomy patients requiring dietary support, we developed a chewing-count measurement device named earable RCC using an earphone-type sensor. Experiments to evaluate the performance of this device were conducted on six healthy volunteers who participated in "gum-chewing tests" and "almond-eating tests." The precision calculated based on the results was >=0.958, indicating that the earphone-type chewing-count measurement device could experimentally distinguish chewing from other actions. In addition, the recall calculated from the test results was >=0.937, showing that the device does not miss chewing actions and can accurately count the number of chews with high probability at the timing of chewing. The experimental results also imply that earphone-type sensors may be used to measure swallowing, occlusal force, and tongue motion. Our future plans include clinical testing of the earphone-type chewing-count measurement device to determine its utility in patients who have undergone gastrectomy. We also intend to expand the application of this device for use in other patients to aid in dementia prevention and dietary support. PMID- 29796233 TI - A Study on Secure Medical-Contents Strategies with DRM Based on Cloud Computing. AB - Many hospitals and medical clinics have been using a wearable sensor in its health care system because the wearable sensor, which is able to measure the patients' biometric information, has been developed to analyze their patients remotely. The measured information is saved to a server in a medical center, and the server keeps the medical information, which also involves personal information, on a cloud system. The server and network devices are used by connecting each other, and sensitive medical records are dealt with remotely. However, these days, the attackers, who try to attack the server or the network systems, are increasing. In addition, the server and the network system have a weak protection and security policy against the attackers. In this paper, it is suggested that security compliance of medical contents should be followed to improve the level of security. As a result, the medical contents are kept safely. PMID- 29796234 TI - Advancements of Medical Image Enhancement in Healthcare Applications. PMID- 29796235 TI - Evoked Hemodynamic Response Estimation to Auditory Stimulus Using Recursive Least Squares Adaptive Filtering with Multidistance Measurement of Near-Infrared Spectroscopy. AB - The performance of functional near-infrared spectroscopy (fNIRS) is sometimes degraded by the interference caused by the physical or the systemic physiological activities. Several interferences presented during fNIRS recordings are mainly induced by cardiac pulse, breathing, and spontaneous physiological low-frequency oscillations. In previous work, we introduced a multidistance measurement to reduce physiological interference based on recursive least squares (RLS) adaptive filtering. Monte Carlo simulations have been implemented to evaluate the performance of RLS adaptive filtering. However, its suitability and performance on human data still remain to be evaluated. Here, we address the issue of how to detect evoked hemodynamic response to auditory stimulus using RLS adaptive filtering method. A multidistance probe based on continuous wave fNIRS is devised to achieve the fNIRS measurement and further study the brain functional activation. This study verifies our previous findings that RLS adaptive filtering is an effective method to suppress global interference and also provides a practical way for real-time detecting brain activity based on multidistance measurement. PMID- 29796236 TI - A Sorting Statistic with Application in Neurological Magnetic Resonance Imaging of Autism. AB - Effect size refers to the assessment of the extent of differences between two groups of samples on a single measurement. Assessing effect size in medical research is typically accomplished with Cohen's d statistic. Cohen's d statistic assumes that average values are good estimators of the position of a distribution of numbers and also assumes Gaussian (or bell-shaped) underlying data distributions. In this paper, we present an alternative evaluative statistic that can quantify differences between two data distributions in a manner that is similar to traditional effect size calculations; however, the proposed approach avoids making assumptions regarding the shape of the underlying data distribution. The proposed sorting statistic is compared with Cohen's d statistic and is demonstrated to be capable of identifying feature measurements of potential interest for which Cohen's d statistic implies the measurement would be of little use. This proposed sorting statistic has been evaluated on a large clinical autism dataset from Boston Children's Hospital, Harvard Medical School, demonstrating that it can potentially play a constructive role in future healthcare technologies. PMID- 29796239 TI - Time to reappraise the therapeutic place of celecoxib. PMID- 29796238 TI - Robot-based intervention may reduce delay in the production of intransitive gestures in Chinese-speaking preschoolers with autism spectrum disorder. AB - Background: Past studies have shown that robot-based intervention was effective in improving gestural use in children with autism spectrum disorders (ASD). The present study examined whether children with ASD could catch up to the level of gestural production found in age-matched children with typical development and whether they showed an increase in verbal imitation after the completion of robot based training. We also explored the cognitive and motor skills associated with gestural learning. Methods: Children with ASD were randomly assigned to two groups. Four- to 6-year-old children with ASD in the intervention group (N = 15) received four 30-min robot-based gestural training sessions. In each session, a social robot, NAO, narrated five stories and gestured (e.g., both hands clapping for an awesome expression). Children with ASD were told to imitate the gestures during training. Age-matched children with ASD in the wait-list control group (N = 15) and age-matched children with typical development (N = 15) received the gestural training after the completion of research. Standardized pretests and posttests (both immediate and delayed) were administered to assess the accuracy and appropriateness of gestural production in both training and novel stories. Children's language and communication abilities, gestural recognition skills, fine motor proficiencies, and attention skills were also examined. Results: Children with ASD in the intervention condition were more likely to produce accurate or appropriate intransitive gestures in training and novel stories than those in the wait-list control. The positive learning outcomes were maintained in the delayed posttests. The level of gestural production accuracy in children with ASD in the delayed posttest of novel stories was comparable to that in children with typical development, suggesting that children with ASD could catch up to the level of gestural production found in children with typical development. Children with ASD in the intervention condition were also more likely to produce verbal markers while gesturing than those in the wait-list control. Gestural recognition skills were found to significantly predict the learning of gestural production accuracy in the children with ASD, with such relation partially mediated via spontaneous imitation. Conclusions: Robot-based intervention may reduce the gestural delay in children with ASD in their early childhood. PMID- 29796240 TI - Interleukin 23 in the skin: role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment. AB - Plaque psoriasis is one of the most common autoimmune skin diseases and is characterized by erythematous, scaly plaques. Many highly effective, targeted therapies have been developed as a result of an improved understanding of the pathogenesis of psoriasis. Using agents that target the central interleukin (IL) 23/IL-17 immune axis, this once difficult-to-treat disease is now among the most effectively treated autoimmune diseases with major clinical improvements possible in around 90% of patients. In this article, we outline the immune mechanisms responsible for the development of psoriasis and provide an overview of the novel IL-23 antagonists being used to manage this chronic skin disease. PMID- 29796237 TI - Self-reported sex differences in high-functioning adults with autism: a meta analysis. AB - Background: Sex differences in autistic symptomatology are believed to contribute to the mis- and missed diagnosis of many girls and women with an autism spectrum condition (ASC). Whilst recent years have seen the emergence of clinical and empirical reports delineating the profile of young autistic girls, recognition of sex differences in symptomatology in adulthood is far more limited. Methods: We chose here to focus on symptomatology as reported using a screening instrument, the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R). In a meta-analysis, we pooled and analysed RAADS-R data from a number of experimental groups. Analysis of variance (ANOVA) searched for the presence of main effects of Sex and Diagnosis and for interactions between these factors in our sample of autistic and non-autistic adults. Results: In social relatedness and circumscribed interests, main effects of Diagnosis revealed that as expected, autistic adults reported significantly greater lifetime prevalence of symptoms in these domains; an effect of Sex, in circumscribed interests, also suggested that males generally reported more prevalent symptoms than females. An interaction of Sex and Diagnosis in language symptomatology revealed that a normative sex difference in language difficulties was attenuated in autism. An interaction of Sex and Diagnosis in the sensorimotor domain revealed the opposite picture: a lack of sex differences between typically developing men and women and a greater prevalence of sensorimotor symptoms in autistic women than autistic men. Conclusions: We discuss the literature on childhood sex differences in relation to those which emerged in our adult sample. Where childhood sex differences fail to persist in adulthood, several interpretations exist, and we discuss, for example, an inherent sampling bias that may mean that only autistic women most similar to the male presentation are diagnosed. The finding that sensorimotor symptomatology is more highly reported by autistic women is a finding requiring objective confirmation, given its potential importance in diagnosis. PMID- 29796241 TI - Pupillary Responses to Illusions of Brightness in Autism Spectrum Disorder. AB - Previous studies indicate that individuals with autism spectrum disorder (ASD) do not experience optical illusions in the same manner as individuals with typical development. This study uses pupillary responses as an objective measure of perception of visual illusions, with the hypothesis that adults with ASD will show weaker pupillary constrictions to the illusions than adults without ASD. An eye-tracker was used to investigate the spontaneous pupillary changes to brightness illusions in adults diagnosed with ASD (N = 11) and in a control group (N = 24). Contrary to the hypothesis, the ASD group showed similar pupillary constrictions to the illusory bright stimuli as the control group. Therefore, this study does not support the idea that individuals with ASD have a veridical perception of these types of illusions and instead suggest that atypical perception of illusions does not constitute a universal characteristic of aspect of high-functioning individuals with ASD. PMID- 29796242 TI - Improved bioactivity of GUMMETAL(r), Ti59Nb36Ta2Zr3O0.3, via formation of nanostructured surfaces. AB - The leading reason for implant revision surgery globally is lack of implant integration with surrounding bone. A new titanium alloy GUMMETAL(r) (Ti59Nb36Ta2Zr3O0.3) is currently used in biomedical devices and has a Young's modulus that is better matched to bone. The surface was subject to NaOH, CaCl2, heat and water treatment (BioGum) after which the surfaces were evaluated using atomic force microscope, scanning electron microscope, X-ray diffractometer and elemental analysis using energy dispersive X-ray. To demonstrate enhanced bone bonding ability and cytocompatibility, apatite formation in simulated body fluid and in vitro stem cell attachment, proliferation and cytoskeleton organisation were examined. The formation of a ~200 nm nanoscale needle-like calcium titanate network on the surface following treatment was revealed and upon soaking in simulated body fluid, the formation of a ~5 um layer of apatite. Metabolic activity of rat bone marrow stem cells on BioGum was increased in comparison to control and the cell number appeared greater, with more elongated morphology as early as 2 h post-seeding. This positions the modification as a simple and potentially universal technology for the improvement of implant integration. PMID- 29796243 TI - The dorsoventral patterning of Musca domestica embryos: insights into BMP/Dpp evolution from the base of the lower cyclorraphan flies. AB - Background: In the last few years, accumulated information has indicated that the evolution of an extra-embryonic membrane in dipterans was accompanied by changes in the gene regulatory network controlled by the BMP/Dpp pathway, which is responsible for dorsal patterning in these insects. However, only comparative analysis of gene expression levels between distant species with two extra embryonic membranes, like A. gambiae or C. albipunctata, and D. melanogaster, has been conducted. Analysis of gene expression in ancestral species, which evolved closer to the amnioserosa origin, could provide new insights into the evolution of dorsoventral patterning in dipterans. Results: Here we describe the spatial expression of several key and downstream elements of the Dpp pathway and show the compared patterns of expression between Musca and Drosophila embryos, both dipterans with amnioserosa. Most of the analyzed gene showed a high degree of expression conservation, however, we found several differences in the gene expression pattern of M. domestica orthologs for sog and tolloid. Bioinformatics analysis of the promoter of both genes indicated that the variations could be related to the gain of several binding sites for the transcriptional factor Dorsal in the Md.tld promoter and Snail in the Md.sog enhancer. These altered expressions could explain the unclear formation of the pMad gradient in the M. domestica embryo, compared to the formation of the gradient in D. melanogaster. Conclusion: Gene expression changes during the dorsal-ventral patterning in insects contribute to the differentiation of extra-embryonic tissues as a consequence of changes in the gene regulatory network controlled by BMP/Dpp. In this work, in early M. domestica embryos, we identified the expression pattern of several genes members involved in the dorsoventral specification of the embryo. We believe that these data can contribute to understanding the evolution of the BMP/Dpp pathway, the regulation of BMP ligands, and the formation of a Dpp gradient in higher cyclorraphan flies. PMID- 29796245 TI - The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes. AB - The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications. PMID- 29796244 TI - 9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-gamma regulation of FABP4. AB - Background: Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13 HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes. Methods: The effects of siRNA silencing of GPR132 gene and of the PPAR-gamma antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14+ cells. Results: 9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14+ cells. Conclusions: We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-gamma-mediated induction of FABP4 by HODEs. PMID- 29796246 TI - Pharmacotherapy of type1 diabetes in children and adolescents: more than insulin? AB - For paediatric patients with type 1 diabetes, intensified insulin therapy with either multiple daily injection or insulin pump therapy is currently the only method of treatment. To optimize this therapy, insulin analogues are fixed parts of all therapy regimens. New ultra-rapid insulins seem to be beneficial not only in adults but also in this age group. New developments in long-acting analogues have demonstrated safety and will be regular in paediatrics, we hope, soon. Furthermore, the psychosocial approach for consideration of real-life aspects becomes more the focus of therapeutic regimens and is implemented into international guidelines. Technical improvements, such as continuous glucose monitoring, particularly in combination with pump therapy, support the great success of rapid-acting analogues by reducing hypoglycaemias. Non-insulin agents such as SGLT2-inhibitors show beneficial aspects in people with type 1 diabetes. For outpatient care with these currently off-label-used drugs, special training for measurement of ketones should be imperative. PMID- 29796247 TI - Managing acute pain in patients who report lactose intolerance: the safety of an old excipient re-examined. AB - Lactose intolerance is exceedingly common, reportedly affecting up to 70% of the world's population, leading to both abdominal and systemic symptoms. Current treatment focuses predominantly on restricting dietary consumption of lactose. Given lactose is one of the most commonly used excipients in the pharmaceutical industry, consideration must be given to the lactose content and therefore safety of pharmaceutical preparations prescribed for patients with lactose intolerance. This article summarizes the current literature examining the likelihood of inducing adverse effects through the administration of lactose-containing pharmaceutical preparations in patients reporting lactose intolerance, describes how to assess this risk on an individual patient basis and reviews suitable analgesic options for this population. A case study is presented detailing a patient reporting lactose intolerance who insists on treatment with the lactose free product codeine/ibuprofen (Nurofen Plus) rather than other codeine-free analgesics. It is important to assess the likelihood of lactose as an excipient inducing symptoms in this scenario, as reluctance to cease codeine could suggest codeine dependence, an issue that is becoming increasingly common in countries such as Australia and Canada. Given codeine dependence is associated with serious sequelae including hospitalization and death, the patient must either be reassured the lactose component in their prescribed analgesics will not induce symptoms or an alternative treatment strategy must be confirmed. General recommendations applying theory from the literature to the management of acute pain in lactose-intolerant patients are discussed and specific treatment options are outlined. Although large inter-individual variability is reported, most lactose-intolerant patients can tolerate the small quantities of lactose found in pharmaceutical preparations. Cumulative lactose exposure can be assessed in patients taking multiple medications while also consuming lactose in the diet. In those sensitive to small quantities of lactose, lactase supplements can be trailed. Additionally, for the analgesic drug classes employed for the management of acute pain, lactose-free formulations, including most oral liquids and dispersible tablets and some oral tablets and capsules, are available. PMID- 29796249 TI - Designing a novel antacid for sensitive populations. PMID- 29796250 TI - Spinal manipulation in the treatment of patients with MRI-confirmed lumbar disc herniation and sacroiliac joint hypomobility: a quasi-experimental study. AB - Background: To investigate the effect of lumbar and sacroiliac joint (SIJ) manipulation on pain and functional disability in patients with lumbar disc herniation (LDH) concomitant with SIJ hypomobility. Methods: Twenty patients aged between 20 and 50 years with MRI-confirmed LDH who also had SIJ hypomobility participated in the trial in 2010. Patients who had sequestrated disc herniation were excluded. All patients received five sessions of spinal manipulative therapy (SMT) for the SIJ and lumbar spine during a 2-week period. Back and leg pain intensity and functional disability level were measured with a numerical rating scale (NRS) and the Oswestry Disability Index (ODI) at baseline, immediately after the 5th session, and 1 month after baseline. Results: A significantly greater mean improvement in back and leg pain was observed in the 5th sessions and 1 month after SMT. Mean changes in ODI in the 5th session and 1 month after treatment also showed significant improvement. The MCIC for NRS and ODI scores in the present study were considered 20 and 6 points, respectively. Therefore, the mentioned improvements were not clinically significant in the 5th session or at 1 month follow-up. Conclusion: Five sessions of lumbar and SIJ manipulation can potentially improve pain and functional disability in patients with MRI-confirmed LDH and concomitant SIJ hypomobility. Trial registration: Irct.ir (Identifier: IRCT2017011924149N33), registered 19 February 2017 (retrospectively registered). PMID- 29796251 TI - How long is enough? Identification of product dry-time as a primary driver of alcohol-based hand rub efficacy. AB - Background: The World Health Organization has called for the development of improved methodologies to evaluate alcohol-based handrub (ABHR) efficacy, including evaluation at "short application times and volumes that reflect actual use in healthcare facilities". The objective of this study was to investigate variables influencing ABHR efficacy, under test conditions reflective of clinical use. Methods: The test product (60% V/V 2-propanol) was evaluated according to a modified EN 1500 methodology, where application volumes of 1 mL, 2 mL, and 3 mL were rubbed until dry. Statistical analyses were performed to investigate the relative influences of product volume, hand size, and product dry-time on efficacy, and hand size and hand contamination on product dry-time. Results: Mean log10 reduction factors (SD) were 1.99 (0.66), 2.96 (0.84) and 3.28 (0.96); and mean dry-times (SD) were 24 s (7 s), 50 s (14 s), and 67 s (20 s) at application volumes of 1 mL, 2 mL, and 3 mL, respectively (p <= 0.030). When data were examined at the individual volunteer level, there was a statistically significant correlation between dry-time and log reduction factor (p < 0.0001), independent of application volume. There was also a statistically significant correlation between hand surface area and dry-times (p = 0.047), but no correlation between hand surface area and efficacy (p = 0.698). Conclusions: When keeping other variables such as alcohol type and concentration constant, product dry-time appears to be the primary driver of ABHR efficacy suggesting that dosing should be customized to each individual and focus on achieving a product dry-time delivering adequate efficacy. PMID- 29796252 TI - Dynamics of colistin and tobramycin resistance among Enterobacter cloacae during prolonged use of selective decontamination of the digestive tract. AB - Background: A high prevalence of colistin resistance among E. cloacae isolates in two intensive care units (ICU) (of 16 and 6 beds) using selective digestive decontamination (SDD) since 1990 instigated a retrospective and prospective investigation to quantify the role of clonal transmission. SDD is topical application of colistin and tobramycin and systemic use of cefotaxime during the first days of ICU-admission. Methods: Multi-resistant E. cloacae (MREb) was defined as ESBL production and/or tobramycin non-susceptibility and/or colistin non-susceptibility. Incidence of acquisition and prevalence of carriage with MREb was determined from microbiological culture results. Results: Colistin-resistant E. cloacae was first detected in November 2009 and carriage was demonstrated in 141 patients until October 2014. Mean incidence of MREb acquisition was 4.61 and 1.86 per 1000 days at risk in ICUs 1 and 2, respectively, and the mean monthly prevalence of MREb in both ICUs was 7.0 and 3.1%, respectively, without a discernible trend in time. Conversion rates from carriage of colistin-susceptible to resistant E. cloacae were 0.20 and 0.13 per 1000 patient days, respectively. Whole genome sequencing of 149 isolates revealed eight clusters, with the number of SNPs of the largest two clusters ranging between 0 and 116 for cluster 1 (n = 49 isolates), and 0 and 27 for cluster 2 (n = 36 isolates), among isolates derived between 2009 and 2014. Conclusions: This study demonstrates a stable low level endemicity of MREb in two Dutch ICUs with prolonged use of SDD, which was characterized by the persistent presence of two clusters, suggesting incidental clonal transmission. PMID- 29796253 TI - Interferon-gamma acts as a regulator in the trade-off between phagocytosis and production performance in dwarf chickens. AB - Background: Interferon-gamma (IFN-gamma) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-gamma reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-gamma on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro (in dwarf chickens). IFN-gamma was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone (FSH) and IFN-gamma were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-gamma, and the mRNA expression levels of follicle stimulating hormone beta subunit (FSH-beta), interferon gamma receptor 1 (IFNGR1), and interferon gamma receptor 2 (IFNGR2) in the pituitary were assessed. Results: Monocyte and macrophage phagocytosis product (PP) was decreased by IFN-gamma treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-gamma in the treatment group was higher than that in the control group at 7 d (P < 0.05), 14 d (P < 0.01), and 21 d (P < 0.01) post-injection. Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection (P < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and 3 wk post injection (P < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection (P < 0.01). In the in vitro experiment, increased mRNA expression levels of FSH-beta, IFNGR1, and IFNGR2 were observed in the treatment group after stimulation with 100 U/mL IFN-gamma for 24 h compared to those in the control group (P < 0.05). Conclusions: IFN-gamma inhibited the phagocytosis of monocytes and macrophages; up-regulated the mRNA expression levels of the FSH-beta, IFNGR1, and IFNGR2; enhanced the secretion of FSH; and improved the laying rate. IFN-gamma might be an important regulator in the trade-off between the immune effect and production performance in dwarf chickens. PMID- 29796248 TI - Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine. AB - Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID- 29796255 TI - Alleviation of mycotoxin biodegradation agent on zearalenone and deoxynivalenol toxicosis in immature gilts. AB - Background: The current study was carried out to evaluate the effects of mycotoxin biodegradation agent (MBA, composed of Bacillus subtilis ANSB01G and Devosia sp. ANSB714) on relieving zearalenone (ZEA) and deoxynivalenol (DON) toxicosis in immature gilts. Methods: A total of forty pre-pubertal female gilts (61.42 +/- 1.18 kg) were randomly allocated to four diet treatments: CO (positive control); MO (negative control, ZEA 596.86 MUg/kg feed and DON 796 MUg/kg feed); COA (CO + 2 g MBA/kg feed); MOA (MO + 2 g MBA/kg feed). Each treatment contained 10 replicates with 1 gilt per replicate. Gilts were housed in an environmentally controlled room with the partially slatted floor. Results: During the entire experimental period of 28 d, average daily gain (ADG) and average daily feed intake (ADFI) of gilts in MO group was significantly reduced compared with those in CO group. The vulva size of gilts was significantly higher in MO group than CO group. In addition, significant increases in the plasma levels of IgA, IgG, IL-8, IL-10 and PRL were determined in MO group compared with that in CO group. ZEA and DON in the diet up-regulated apoptotic caspase-3 in ovaries and uteri, along with down-regulated the anti-apoptotic protein Bcl-2 in ovaries. The supplementation of MBA into diets co-contaminated with ZEA and DON significantly increased ADG, decreased the vulva sizes, reduced the levels of IgG, IL-8 and PRL in plasma, and regulated apoptosis in ovaries and uteri of gilts. Conclusions: The present results indicated that feeding diet contaminated with ZEA and DON simultaneously (596.86 MUg/kg + 796 MUg/kg) had detrimental effects on growth performance, plasma immune function and reproductive status of gilts. And MBA could reduce the negative impacts of these two toxins, believed as a promising feed additive for mitigating toxicosis of ZEA and DON at low levels in gilts. PMID- 29796258 TI - Guest editorial for May issue. PMID- 29796254 TI - Integrative analysis of indirect calorimetry and metabolomics profiling reveals alterations in energy metabolism between fed and fasted pigs. AB - Background: Fasting is a simple metabolic strategy that is used to estimate the maintenance energy requirement where the energy supply for basic physiological functions is provided by the mobilization of body reserves. However, the underlying metabolic components of maintenance energy expenditure are not clear. This study investigated the differences in heat production (HP), respiratory quotient (RQ) and plasma metabolites in pigs in the fed and fasted state, using the techniques of indirect calorimetry and metabolomics. Methods: Nine barrows (45.2 +/- 1.7 kg BW) were fed corn-soybean based meal diets and were kept in metabolism crates for a period of 14 d. After 7 d adaptation, pigs were transferred to respiratory chambers to determine HP and RQ based on indirect calorimetry. Pigs were fed the diet at 2,400 kJ ME/(kg BW0.6.d) during d 8 to 12. The last 2 d were divided into 24 h fasting and 48 h fasting treatment, respectively. Plasma samples of each pig were collected from the anterior vena cava during the last 3 d (1 d while pigs were fed and 2 d during which they were fasted). The metabolites of plasma were determined by high-resolution mass spectrometry using a metabolomics approach. Results: Indirect calorimetry analysis revealed that HP and RQ were no significant difference between 24 h fasting and 48 h fasting, which were lower than those of fed state (P < 0.01). The nitrogen concentration of urine tended to decrease with fasting (P = 0.054). Metabolomics analysis between the fed and fasted state revealed differences in 15 compounds, most of which were not significantly different between 24 h fasting and 48 h fasting. Identified compounds were enriched in metabolic pathways related to linoleic acid metabolism, amino acid metabolism, sphingolipid metabolism, and pantothenate and CoA biosynthesis. Conclusion: These results suggest that the decreases in HP and RQ of growing pigs under fasting conditions were associated with the alterations of linoleic acid metabolism and amino acid metabolism. The integrative analysis also revealed that growing pigs under a 24-h fasting were more appropriate than a 48-h fasting to investigate the metabolic components of maintenance energy expenditure. PMID- 29796256 TI - Association of residual feed intake with abundance of ruminal bacteria and biopolymer hydrolyzing enzyme activities during the peripartal period and early lactation in Holstein dairy cows. AB - Background: Residual feed intake (RFI) in dairy cattle typically calculated at peak lactation is a measure of feed efficiency independent of milk production level. The objective of this study was to evaluate differences in ruminal bacteria, biopolymer hydrolyzing enzyme activities, and overall performance between the most- and the least-efficient dairy cows during the peripartal period. Twenty multiparous Holstein dairy cows with daily ad libitum access to a total mixed ration from d - 10 to d 60 relative to the calving date were used. Cows were classified into most-efficient (i.e. with low RFI, n = 10) and least efficient (i.e. with high RFI, n = 10) based on a linear regression model involving dry matter intake (DMI), fat-corrected milk (FCM), changes in body weight (BW), and metabolic BW. Results: The most-efficient cows had ~ 2.6 kg/d lower DMI at wk 4, 6, 7, and 8 compared with the least-efficient cows. In addition, the most-efficient cows had greater relative abundance of total ruminal bacterial community during the peripartal period. Compared with the least efficient cows, the most-efficient cows had 4-fold greater relative abundance of Succinivibrio dextrinosolvens at d - 10 and d 10 around parturition and tended to have greater abundance of Fibrobacter succinogenes and Megaspheara elsdenii. In contrast, the relative abundance of Butyrivibrio proteoclasticus and Streptococcus bovis was lower and Succinimonas amylolytica and Prevotella bryantii tended to be lower in the most-efficient cows around calving. During the peripartal period, the most-efficient cows had lower enzymatic activities of cellulase, amylase, and protease compared with the least-efficient cows. Conclusions: The results suggest that shifts in ruminal bacteria and digestive enzyme activities during the peripartal period could, at least in part, be part of the mechanism associated with better feed efficiency in dairy cows. PMID- 29796261 TI - Listening to and letting pain speak: poetic reflections. AB - The humanities invite opportunities for people to describe through their metaphors, symbols and language a means in which to interpret their pain and reinterpret their new lived experiences. The patient and family all live with pain and can only use their pain narratives of that experience to confront or even to begin to understand the quantifiable discipline of medicine. The patient and family narratives act to retain meaning within a lived pained experience. These narratives add meaning to the person as a stay against only having a clinical-pathological understanding of what is happening to our body and as a person. We need to understand the pathology pain while also being mindful of suffering. In this article, the theoretical and scientific approach to pain research and clinical practice intersects with the philosophical, ontological and reflective lived experience of the person living with pain. Through unique pain narratives, poetry and stories as a means of offering empathy and understanding as healing, the humanities in medicine bring into meaning another kind of therapy equal to the evidence-based medicine clinicians and researchers use to seek a cure. In this way, the medical humanities are addressing the person's healing through the reduction of suffering and isolation by letting pain speak while others can focus in on their medical knowledge/practice and research while 'finding' a cure. Listening to pain opens-up to the possibility that much can be learned through multiple expressions of the pain narrative. This article provides an invitation to learn how we might articulate and listen to pain carefully and differently. PMID- 29796259 TI - Analgesic reduction during an interdisciplinary pain management programme: treatment effects and processes of change. AB - Long-term use of opioid medication is associated with a host of negative effects on health and quality of life. Guidelines state that people with chronic pain taking high doses of opioids without benefit should be supported to discontinue them. Little research has investigated psychological processes associated with analgesic use and tapering. This study investigated (1) analgesic use pre- and post-participation in an interdisciplinary pain management programme and its relationship to functioning and (2) psychological processes associated with analgesic use. Opioid use was associated with poorer functioning at baseline. Participating in an interdisciplinary pain management programme was associated with reductions in opioid dose and number of classes of analgesics used. Reductions in analgesic use were associated with improvements in functioning. Psychological inflexibility was associated with using higher doses of opioid medication and with using a greater number of classes of analgesics. Psychological flexibility appears relevant in explaining analgesic use. Future research could focus on targeting this process to improve tapering outcomes. PMID- 29796260 TI - Understanding the link between feelings of mental defeat, self-efficacy and the experience of chronic pain. AB - Objectives: 'Mental defeat' (MD) has been identified among people with chronic pain as a type of self-processing related to social role and rank. Research has linked it to anxiety, pain interference and functional disability. The relationship between MD and other cognitive constructs, such as hopelessness and depression, remains poorly understood. This study considers the association between MD, pain symptomatology and self-efficacy in the context of other cognitive factors. Methods: In total, 59 participants completed a questionnaire pack assessing anxiety, depression, hopelessness, pain catastrophising and MD in order to examine the relationship with pain symptomatology and self-efficacy. Results: Linear multiple regression analyses showed that anxiety was most strongly associated with pain symptomatology, accounting for 26% of the variance, while catastrophising showed the strongest association with sensory pain and MD the strongest association with affective pain. Finally, MD was found to be strongly associated with pain-related self-efficacy, accounting for 47% of the variance. Conclusion: This research has demonstrated the potential importance of assessing MD in chronic pain patients, suggesting that targeting these cognitions during interventions and therapy could be valuable. Furthermore, the study indicates that MD differs from related cognitive constructs involved in pain, such as depression, hopelessness and catastrophising. PMID- 29796262 TI - Evaluation of uptake and effect on patient-reported outcomes of a clinician and patient co-led chronic musculoskeletal pain self-management programme provided by the UK National Health Service. AB - In the United Kingdom, chronic pain affects approximately 28 million adults, creating significant healthcare and socio-economic costs. The aim was to establish whether a programme designed to use best evidence of content and delivery will be used by patients with significant musculoskeletal pain problems. Of 528 patients recruited, 376 participated in a 7-week-long group-based self management programme (SMP) co-delivered by clinical and lay tutors. Of these, 308 patients (mean age, 53 years; 69% females, 94% White) completed at least five SMP sessions. Six months after pre-course assessment, participants reported significantly improved patient activation and health status, lower depression and anxiety scores, decreased pain severity and interference, and improved self management skills. There were no improvements in health state and pain self efficacy. Uptake rate was 71% and completion 82%. The results should be of value to commissioners of pathways of care for the large numbers of patients attending the English NHS for chronic musculoskeletal pain. PMID- 29796263 TI - Five years of a community pain service solution-focused pain management programme: extended data and reflections. AB - 1. This article aims to provide a long-term update 2 years on from our initial paper and summarises service evaluation data collected from 21 pain management programmes, using a solution-focused approach in a community pain service. 2. An examination of the larger baseline and subsequent follow-up data suggests an improvement in participants' function, pain self-efficacy and mental well-being following CPS PMP, and corroborates the findings of the earlier dataset. 3. Additional findings suggest that CPS PMP may help pain interfere less in participants' lives (post-PMP and at 10-week follow-up) and that improvements in mental well-being and self-efficacy are maintained on a long-term basis (at 6- and 12-month follow-up). Limitations of the data are discussed. 4. The article also discusses the nature of community healthcare services for chronic pain, including how we view PMP treatment intensity, deliver cost effectiveness, measure outcomes and support patients post-PMP. 5. It is suggested that effective, meaningful PMPs can be facilitated successfully by multi-professional teams in the community, at arguably lower cost than secondary/tertiary settings, while enabling convenient and long-lasting integration of self-management into people's lives. PMID- 29796264 TI - Using patient experiences to develop services for chronic pain. AB - Purpose: The aim of this study was to improve the overall experience for patients using chronic pain services at a large teaching hospital in England. Experience based co-design methodology was used to gain a greater understanding of patients' experiences and to produce a list of priorities for change when improving the patient experience. Method: A total of seven video-recorded patient interviews were conducted to capture a range of patient experiences of using the chronic pain service. The interviews were analysed to identify 'touchpoints' which are areas in which patients experienced a heightened emotional response to their interaction with the service or staff. A short trigger film was compiled to illustrate these touchpoints to staff and gain their commitment to improve patients' experiences when using the service. A patient experience event was held at which patients discussed the touchpoints and identified the most significant areas for change that would improve their experiences of using the chronic pain service. Results: A wide range of touchpoints were identified. The lack of information provided before arriving for a procedure and the need for a short debrief after clinic were prioritised for improvement. Patients valued the development of good relationships with clinic staff and feeling properly listened to for the first time. The patient experience event allowed the key points patients would like to know before a procedure, to be drawn up in a list, which could be passed onto staff. Conclusion: This study featured collaboration between patients and staff to improve patients' experiences of using chronic pain services. Through patient participation, a comprehensive list of recommendations for service improvement was produced, and possible solutions were identified. The involvement of patients in driving change and re-designing services is shaping a more patient-centred chronic pain clinic and improving the experience for all the patients who use the service. PMID- 29796265 TI - Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections. AB - : Traditional metronidazole dosing regimens utilize an every 8 h dosing strategy to treat anaerobic and mixed anaerobic infections. However, pharmacokinetic data demonstrate that the half-life of metronidazole is 8-12 h and blood levels at 12 h exceed the in vitro minimum inhibitory concentration (MIC) for most anaerobic infections. The primary objective of this study was to evaluate the frequency of clinical cure among patients who received metronidazole every 12 h compared with those who received an every 8 h frequency. Secondary endpoints included duration of antibiotics, hospital length of stay, escalation of antibiotic therapy, microbiologic cure, and mortality. Methods: This retrospective, single-center, pre-post intervention study of 200 patients between June 2014 to July 2016. Results: No significant differences in clinical cure for every 12 h versus every 8 h metronidazole dosing regimens (85% for both groups, p = 1.00) were found. There were no differences in any of the secondary endpoints, with a mean duration of antibiotic therapy being 5.9 versus 5.8 days and a hospital length of stay averaging 8.1 versus 6.7 days for the 12- and 8-h dosing groups, respectively (p > 0.05). Discussion: Findings validate pharmacokinetic data suggesting that an extended metronidazole dosing interval effectively treats anaerobic infections. PMID- 29796266 TI - Inside help: An integrative review of champions in healthcare-related implementation. AB - Background/aims: The idea that champions are crucial to effective healthcare related implementation has gained broad acceptance; yet the champion construct has been hampered by inconsistent use across the published literature. This integrative review sought to establish the current state of the literature on champions in healthcare settings and bring greater clarity to this important construct. Methods: This integrative review was limited to research articles in peer-reviewed, English-language journals published from 1980 to 2016. Searches were conducted on the online MEDLINE database via OVID and PubMed using the keyword "champion." Several additional terms often describe champions and were also included as keywords: implementation leader, opinion leader, facilitator, and change agent. Bibliographies of full-text articles that met inclusion criteria were reviewed for additional references not yet identified via the main strategy of conducting keyword searches in MEDLINE. A five-member team abstracted all full-text articles meeting inclusion criteria. Results: The final dataset for the integrative review consisted of 199 unique articles. Use of the term champion varied widely across the articles with respect to topic, specific job positions, or broader organizational roles. The most common method for operationalizing champion for purposes of analysis was the use of a dichotomous variable designating champion presence or absence. Four studies randomly allocated of the presence or absence of champions. Conclusions: The number of published champion related articles has markedly increased: more articles were published during the last two years of this review (i.e. 2015-2016) than during its first 30 years (i.e. 1980-2009).The number of champion-related articles has continued to increase sharply since the year 2000. Individual studies consistently found that champions were important positive influences on implementation effectiveness. Although few in number, the randomized trials of champions that have been conducted demonstrate the feasibility of using experimental design to study the effects of champions in healthcare. PMID- 29796267 TI - Physical activity mediates the association between personality and biomarkers of inflammation. AB - Objectives: The current study investigated whether personality traits and facets were associated with interleukin-6, C-reactive protein, and fibrinogen, and whether physical activity mediated the relationship between personality and biomarkers of inflammation. Methods: Personality was assessed in the Midlife Development in the United States study using the Multi-Dimensional Personality Questionnaire and Midlife Development Inventory personality scale. Data were included from 960 participants (mean age = 57.86 years, standard deviation = 11.46). Personality was assessed from 2004 to 2009. Serum levels of interleukin 6, fibrinogen, and C-reactive protein were assessed in 2005-2009 as part of the Midlife Development in the United States biomarkers subproject. Results: Lower neuroticism was associated with elevated interleukin-6, and achievement was associated with lower fibrinogen. Higher physical activity was associated with lower interleukin-6 and C-reactive protein. Mediation models suggested that physical activity mediated the associations between achievement and both interleukin-6 and C-reactive protein. Discussion: Physical activity is an important factor in the Health Behavior Model of personality and explains some of the associations between personality and inflammation. These findings contribute to the fields of aging and health by linking individual difference factors to markers of inflammation, and showing that these processes may function partially through specific behaviors, in this case physical activity. PMID- 29796268 TI - First report of African tick-bite fever in a South American traveler. AB - We report a clinical case of African tick-bite fever in a Brazilian traveler right after his return from South Africa. Definitive diagnosis was supported by seroconversion between acute-phase and convalescent-phase serum samples, detection of rickettsial DNA in skin lesions, and in vitro culture of Rickettsia africae from the patient's skin. Most of the previous reported cases of African tick-bite fever were confirmed solely by serological or/and molecular methods. Through this first confirmed case of African tick-bite fever in Brazil, it is quite possible that other cases are occurring unnoticed by the health authorities, requiring a greater vigilance in traveler's medicine in South America. PMID- 29796269 TI - Intra- and extracapsular synovial chondromatosis of the temporomandibular joint: Rare case and review of the literature. AB - Synovial chondromatosis is a benign disease which most commonly appears in large joints and only rarely affects the temporomandibular joint. The diagnosis is quite difficult due to the fact that a large swelling in the preauricular area and the radiographic findings may be misdiagnosed as other benign or malignant diseases. We report an unusual case of intra- and extracapsular chondromatosis of 25 osteochondral loose bodies in the right temporomandibular joint. PMID- 29796270 TI - Successful use of balloon tamponade in the management of postpartum hemorrhage in a case of bicornuate uterus. AB - Worldwide 50%-70% of all cases of maternal morbidity have been attributed to postpartum hemorrhage. This report discusses a case of bicornuate uterus in a term pregnancy. The delivery was by cesarean section, which was followed by massive postpartum hemorrhage, managed successfully with balloon tamponade. This is the second reported case of successful management of post partum hemorrhage in a bicornuate uterus with balloon tamponade. A 22-year-old primigravida at 39 weeks of gestational age presented with vaginal leaking of clear fluid. Cesarean section was done due to meconium stained liquor in early labor; with an incidental finding of bicornuate uterus followed by massive postpartum hemorrhage managed successfully with balloon tamponade. The use of uterine balloon tamponade as an effective method to control postpartum hemorrhage has been studied extensively, but use in cases of hemorrhage associated with uterine malformations has not been reported much in literature. Use of uterine balloon tamponade in case of uterine malformations has been highlighted in our case as an effective non-surgical method to control hemorrhage. PMID- 29796271 TI - Ceruminous adenoma mimicking otitis externa. AB - Ceruminous adenoma is an extremely rare condition that arises in the external auditory canal. The right ear canal in a 32-year-old man was obstructed by a ceruminous adenoma mimicking otitis externa and its symptoms. The lesion was resected under microscopic view using a transcanal approach. There were no tumor related symptoms postoperatively and he has been disease free for 1 year after surgery. PMID- 29796272 TI - Symptomatic recurrent varicose veins due to primary avalvular varicose anomalies (PAVA): A previously unreported cause of recurrence. AB - A 56-year-old woman presented in 2006 with symptomatic primary varicose veins in her right leg. Venous duplex ultrasonography at that time showed what appeared to be "neovascular tissue" around the saphenofemoral junction. However, there had been no previous trauma or surgery in this area. This appearance has subsequently been described as primary avalvular varicose anomalies. She underwent endovenous treatment at that time. In 2018, she presented with symptomatic recurrent varicose veins of the same leg. Venous duplex ultrasonography showed successful ablation of the great saphenous and anterior accessory saphenous veins. All of the recurrent venous reflux was arising from the primary avalvular varicose anomalies. This report shows that primary avalvular varicose anomalies is a previously unreported cause of recurrent varicose veins and leads us to suggest that if found, treatment of the primary avalvular varicose anomalies should be considered at the primary procedure. PMID- 29796274 TI - Cryptococcal pleural infection in a recurrent pleural effusion: a case report. AB - Cryptococcal pleural infection is rare with about 50 cases reported. It tends to occur in immunocompromised individuals. We describe a 38-year-old male who presented with a lymphocytic exudative right pleural effusion and a raised pleural fluid adenosine deaminase (ADA) level. He was initially treated for pleural tuberculosis, but presented again with worsening pleural effusion 6 weeks later. A thoracoscopic pleural biopsy revealed chronic nodular granulomatous pleuritis with cryptococcal organisms present. The repeat pleural fluid culture was positive for Cryptococcus neoformans. He was started on intravenous amphotericin B and oral flucytosine for 1 week, and then continued on oral fluconazole. He was subsequently diagnosed to have acute myeloid leukaemia. His peripheral blood film showed presence of blast cells (33%), with flow cytometry showing increased myeloblast population. Lymphocytic exudative pleural effusions with raised ADA levels in an immunocompromised patient can be due to opportunistic fungal infections. PMID- 29796273 TI - Bilateral anterior interosseous nerve syndrome with 6-year interval. AB - Flexor pollicis longus paralysis related to idiopathic anterior interosseous nerve syndrome is well known, but few reports exist on bilateral disease. A 24 year-old man with no personal or family history of neurological disease developed isolated total loss of active flexion of the right thumb's interphalangeal joint after undergoing a wrist arthroscopy. Surgical exploration 5 weeks after onset showed flexor pollicis longus tendon to be intact; anterior interosseous nerve decompression was done with no abnormalities found. Because of persistent paralysis, electromyography was performed showing findings consistent with anterior interosseous nerve syndrome. After 7 months without recovery, the patient underwent tendon transfer. After 6 years, the patient presented with left sided isolated flexor pollicis longus paralysis and electromyography indicated anterior interosseous nerve syndrome. Examination 9 months after onset showed persistent complete flexor pollicis longus paralysis but by 15 months spontaneous complete recovery had occurred. Anterior interosseous nerve syndrome can occur bilaterally and is likely to resolve completely without intervention but recovery may take longer than a year. PMID- 29796275 TI - Eosinophilia as a treatable trait in three patients with asthma and COPD. AB - The combination of asthma and chronic obstructive pulmonary disease (COPD) in an individual can present significant challenges to achieving satisfactory outcomes. More recently, the concepts of precision medicine and treatable traits have arisen as promising tools to improve care for this group. In this series, we present three cases of patients with features of both asthma and COPD in addition to peripheral blood eosinophilia. The novel implementation of personalized management of the individual based on this treatable trait (eosinophilia) resulted in significant benefits. These benefits included improvement in symptoms, lung function, and a marked decline in critical care admissions and exacerbation rates. PMID- 29796276 TI - Successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy-induced tumour lysis in a patient with small-cell lung carcinoma. AB - Here, we report the case of a patient with small-cell lung carcinoma (SCLC) who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This syndrome may be associated with chemotherapy-induced tumour lysis. Our patient was successfully treated with tolvaptan. A 70-year-old man was diagnosed with SCLC and was treated with carboplatin and etoposide. Episodes of hyponatremia occurred after every four cycles of chemotherapy that achieved tumour reduction; however, the hyponatremia was improved by temporary administration of tolvaptan. In SIADH associated with chemotherapy-induced tumour lysis, tolvaptan may improve hyponatremia and enable the continued administration of effective chemotherapy. PMID- 29796277 TI - Facial flushing on upper limb exertion: a rare presentation of superior vena cava obstruction. AB - Infection remains a significant problem for patients with cardiac-implantable electronic devices (CIEDs) but can be difficult to diagnose. We describe an unusual presentation of CIED infection in a patient with abandoned pacemaker leads. A 27-year-old male presented with facial flushing on upper but not lower limb exertion due to superior vena cava (SVC) obstruction, as well as pleuritic chest pain due to septic emboli. This was successfully treated with antibiotics and complete endovascular extraction of the pacemaker leads. Upper limb exertional facial flushing may be a useful clinical sign for the diagnosis of SVC obstruction. This case report also describes a rare presentation of CIED infection. PMID- 29796278 TI - Pleuroparenchymal fibroelastosis after haematopoietic stem cell transplantation without graft-versus-host disease findings. AB - Although rare, pleuroparenchymal fibroelastosis (PPFE) is a serious late-onset complication of haematopoietic stem cell transplantation (HSCT). It remains unclear whether graft-versus-host disease (GVHD) is involved in the development of PPFE. We report the case of a patient with PPFE after HSCT. The patient experienced pneumothorax repeatedly despite surgical treatment. A surgical specimen demonstrated PPFE findings, without evidence of GVHD. In this case, development of PPFE was not associated with GVHD, and immunosuppressive therapy did not improve pulmonary function. Surgical biopsy is recommended for precise treatment and elucidation of pathogenesis in each suspected PPFE patient. PMID- 29796279 TI - Orthodeoxia as a presentation of intravascular large B cell lymphoma. AB - Intravascular large B cell lymphoma (IVLBCL) is a rare and aggressive subtype of diffuse large B cell lymphoma, of which clinical presentations are highly variable among geographical areas. A case series of IVLBCL patients from Asian countries reported the disease to be more aggressive and associated with hemophagocytic syndrome than in cases from Western countries. Although published articles recently revealed hypoxemia as a presentation in IVLBCL patients, orthodeoxia has never been documented. A 71-year-old man presented with prolonged fever, cough, exertional dyspnoea, and orthodeoxia, later developing hypoxemic respiratory failure and refractory septic shock. Eventually, IVLBCL was diagnosed by random skin biopsy and bone marrow biopsy because of a high index of suspicion. We demonstrated the first case of orthodeoxia as an initial presentation of IVLBCL, clinically compatible with Asian-variant IVLBCL, which is commonly fatal and diagnostically challenging. PMID- 29796280 TI - Summer at the beach: spatio-temporal patterns of white shark occurrence along the inshore areas of False Bay, South Africa. AB - Background: Understanding white shark (Carcharodon carcharias) habitat use in coastal areas adjacent to large cities, is an important step when formulating potential solutions to the conservation conflict that exists between humans and large predatory sharks. In this study, we present the findings of a 2.5-year study of white shark occurrence and movement patterns adjacent to the City of Cape Town in False Bay, South Africa, with a focus on spring and summer months. Fifty-one white sharks were monitored annually at three offshore and twelve inshore sites by VR2 acoustic receivers, over 975 days from 1 May 2005 to 31 December 2007. Results: Occurrence patterns at inshore sites during spring and summer were analysed using a generalized additive mixed model (GAMM) with a spatial term (longitude, latitude), time of day and year included as explanatory variables for site use. We found that sharks occurred more frequently at inshore sites along the northern and northwestern shores, compared to the rest of the bay, and they transitioned most frequently between four adjacent beach sites that encompass the most popular recreational water use areas in Cape Town. There was significant diel variation, with higher shark occurrence around midday, and a peak in shark occurrence in 2005, when human-shark interactions also peaked. However, we found no effect of shark size on occurrence patterns at inshore sites. Conclusions: White sharks showed the highest levels of occurrence at specific inshore sites between Muizenberg and Strandfontein beach, and thus inclusion of these sites within False Bay's marine protected area (MPA) network or recognition as Ecological or Biological Significant Areas (EBSAs) should be a future consideration. These insights into white shark habitat use at inshore sites in False Bay are important for successfully applying the principles of marine spatial planning (MSP) and for making science-based policy decisions. Furthermore, this information can be used to reduce potential shark-human conflict by incorporating it into future shark safety education campaigns. PMID- 29796283 TI - A case of decompression illness not responding to hyperbaric oxygen. AB - Background: The case reinforces the importance of stepping back and looking at every possibility along with multiple co-existing pathologies. It takes into account the thought process of multiple systems and a multidisciplinary team approach. Learning points to take are that decompression illness can present atypically, but one must exclude other causes. Case presentation: We present the case of a 42-year-old male from the West Midlands, UK, who attended the emergency department post-scuba diving with confusion, light-headedness, left arm weakness, and bilateral paraesthesia of the hands. Post-diving, he displayed typical symptoms of decompression illness. He attended the hyperbaric decompression chamber before attending the emergency department but to no resolve. A computed tomography of the head showed no signs of intracranial pathology. He had another session in the hyperbaric oxygen chamber but to no success. Upon admission, his blood showed polycythaemia. His saturation had dropped to 91% on room air, and a computed tomography pulmonary angiogram revealed no obvious cause. A magnetic resonance imaging of his head revealed some deep periventricular ischaemic changes, old and new, however no signs of gas embolism or poor flow. A bubble echo confirmed a patent foramen ovale. A leptospirosis and a vasculitis screen were both negative. Symptoms had slowly improved but he was left with a left arm motor weakness, and the team was left puzzled as to what could have caused his signs and symptoms. Through a diagnosis of exclusion, decompression sickness was the conclusive diagnosis. The patient made a full recovery. Conclusions: Decompression illness results as a sudden decrease in pressures during underwater ascent; it is caused by nitrogen bubbles forming in tissue. Additionally, a patent foramen ovale allows arterial gas emboli to cause further harm. Type 2 decompression sickness is the more severe form and includes neurological, respiratory, and cardiovascular symptoms. PMID- 29796281 TI - Emotion dysregulation in attention-deficit/hyperactivity disorder and borderline personality disorder. AB - There is ongoing debate on the overlap between Attention-Deficit/Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD), particularly regarding emotion dysregulation (ED). In this paper, we present a narrative review of the available evidence on the association of these two disorders from several standpoints. First, we discuss the unique and shared diagnostic criteria for ADHD and BPD, focusing particularly on ED. We consider the methodology of ecological momentary assessment and discuss why this approach could be an alternative and more accurate way to qualitatively distinguish between ADHD and BPD. We summarise key findings on the genetic and environmental risk factors for ADHD and BPD and the extent to which there are shared or unique aetiological and neurobiological risk factors. Finally, we discuss the clinical relevance of considering both disorders in the assessment of patients presenting with trait-like behavioural syndromes, distinguishing the two conditions and implications for treatment. PMID- 29796282 TI - Negative urgency partially accounts for the relationship between major depressive disorder and marijuana problems. AB - Background: To goal of this study was to better understand mechanisms underlying associations between Major Depressive Disorder (MDD) and marijuana use and problems. Specifically, it was hypothesized that negative urgency (NU), the tendency to act rashly while experiencing negative mood states, would uniquely (compared to other impulsivity traits: positive urgency, sensation seeking, premeditation, and perseverance) account for the relationship between MDD and marijuana use and problems. Methods: Data were collected from a sample (N = 357) of veterans (M age = 33.63) recruited from a Veterans Affairs hospital who used marijuana at least once in their lifetime. Participants completed the SCID-NP to assess MDD, a marijuana problems scale, a Time-Line Follow-back to assess six month marijuana use, and the UPPS-P Impulsive Behavior Scale for impulsivity. Results: Path analysis was conducted using bootstrapped (k = 20,000) and bias corrected 95% confidence intervals (CIs) to estimate mediation (indirect) effects, controlling for age, sex, and race. Analyses revealed a significant direct effect of MDD on NU and NU on marijuana problems. Regarding mediational analyses, there was a significant indirect effect of MDD on marijuana problems via NU. The direct effect of MDD on marijuana problems was reduced, but remained significant, suggesting partial mediation. No other impulsivity scales accounted for the relationship between MDD and marijuana problems. In predicting marijuana use, there were no significant indirect effects for any impulsivity traits, including NU, despite significant bivariate associations between use and NU and MDD. Conclusions: Results suggest that high levels of NU may partially explain associations between MDD and marijuana problems, but not marijuana use. No other facets of impulsivity accounted for the relationship between MDD and marijuana use or problems, underscoring the specificity of NU as a putative mechanism and the importance of assessing NU in treatment settings. PMID- 29796284 TI - Provider preferences for postoperative analgesia in obese and non-obese patients undergoing ambulatory surgery. AB - Background: Few guidelines exist on safe prescription of postoperative analgesia to obese patients undergoing ambulatory surgery. This study examines the preferences of providers in the standard treatment of postoperative pain in the ambulatory setting. Methods: Providers from five academic medical centers within a single US city were surveyed from May-September 2015. They were asked to provide their preferred postoperative analgesic routine based upon the predicted severity of pain for obese and non-obese patients. McNemar's tests for paired observations were performed to compare prescribing preferences for obese vs. non obese patients. Fisher's exact tests were performed to compare preferences based on experience: > 15 years vs. <=15 years in practice, and attending vs. resident physicians. Results: A total of 452 providers responded out of a possible 695. For mild pain, 119 (26.4%) respondents prefer an opioid for obese patients vs. 140 (31.1%) for non-obese (p = 0.002); for moderate pain, 329 (72.7%) for obese patients vs. 348 (77.0%) for non-obese (p = 0.011); for severe pain, 398 (88.1%) for obese patients vs. 423 (93.6%) for non-obese (p < 0.001). Less experienced physicians are more likely to prefer an opioid for obese patients with moderate pain: 70 (62.0%) attending physicians with > 15 years in practice vs. 86 (74.5%) with <=15 years (p = 0.047), and 177 (68.0%) attending physicians vs. 129 (83.0%) residents (p = 0.002). Conclusions: While there is a trend to prescribe less opioid analgesics to obese patients undergoing ambulatory surgery, these medications may still be over-prescribed. Less experienced physicians reported prescribing opioids to obese patients more frequently than more experienced physicians. PMID- 29796285 TI - Myelodysplastic syndrome in an infant with constitutional pure duplication 1q41 qter. AB - We report on a Japanese female infant as the fourth patient with the constitutional pure duplication 1q41-qter confirmed by chromosomal microarray and as the first who developed myelodysplastic syndrome (MDS) among those with the constitutional 1q duplication. Common clinical features of the constitutional pure duplication 1q41-qter include developmental delay, craniofacial characteristics, foot malformation, hypertrichosis, and respiratory insufficiency. The association between MDS and the duplication of the genes in the 1q41-qter region remains unknown. PMID- 29796286 TI - A novel 8-bp duplication in ADAT3 causes mild intellectual disability. AB - Inosine is a base located at wobble position 34 of the tRNA anticodon stem-loop, enabling the recognition of more than one codon in the translation process. A heterodimer consists of ADAT3 and ADAT2 and is involved in the adenosine-to inosine conversion in tRNA. Here, we report the second novel ADAT3 mutation in a patient with microcephaly, intellectual disability, and hyperactivity. These findings constitute a second mutation and expand the clinical spectrum of extremely rare ADAT3 mutations. PMID- 29796288 TI - Flock composition, breeding strategies and farmers' traits of interest evaluation of Wollo highland sheep and their F1 crosses. AB - Background: Sheep production is a major component of the livestock sector in Ethiopia. The country owing to the large population of 30.70 million estimated numbers of sheep in the country and out of which about 72.14% are females, and 27.86% are males with diverse genetic resources. The real value of indigenous breeds was often under-estimated mostly due to their poor appearance and relatively low productivity. Developing countries in most cases opt for exotic breeds to increase animal productivity through crossbreeding or breed substitution without properly investigating the production potential of the indigenous breeds. The main objective of the research was to identify sheep flock composition and structure, farmers' traits of interest and breeding objective of Wollo highland sheep, and their F1 crossbreed progenies. Results: Smallholder farmers' flock synthesized from breeding ewes, breeding rams, pre-weaned ewe lambs, pre-weaned ram lambs, unproductive ewes, castrated and fattened rams, with the percentage coverage of 29.2, 13.3, 15.5, 16.5, 12.4, and 12.5%, respectively. The maximum number of flock size was 289.0 sheep per flock and higher in the third stratum. The off-take rate percentage of the three strata presented as 21.9% in 1st stratum, 12% in the 2nd stratum, and 16.4% in the 3rd stratum and higher off-take rate recorded in the first stratum. Sheep producer's traits of interest ranked by growth rate (first), body size (second) and marketing value was third rank. Communal breeding (random mating), village based controlled breeding, mixed type and private ram controlled breeding practice were comprised of 39.7, 61.7, 52 and 71.3%, respectively. The percentages of ewes per flock composition were presented as 36.5, 27.1 and 25.5%, respectively in the 3rd stratum, 2nd stratum and 3rd stratum in the order of their importance's. Conclusion: Genetic improvement practices at smallholder sheep producers situation was showing promising outcome with indigenous Washera F1 crossbred lambs and which designated for weaning rate, body size, marketing age, age at first lambing, good temperament and large litter size in the order of their rank. The contemporary breeding practice tendency indicated that, reduced flock size to improve flock productivity via crossbreeding practices. PMID- 29796287 TI - Effect of adjusting the combination of budesonide/formoterol on the alleviation of asthma symptoms. AB - Background: The combination of budesonide + formoterol (BFC) offers the advantages of dose adjustment in a single inhaler according to asthma symptoms. We analyzed the relationship between asthma symptoms in terms of peak expiratory flow (PEF) and dose adjustment by the patient. Methods: Twenty-eight patients with asthma who used BFC for alleviation of their symptoms (12 men, 16 women; 60 years old) were instructed that the inhaled BFC dose could be increased to a maximum of 8 inhalations per day according to symptom severity. Patients measured and recorded PEF every morning and evening in their asthma diary along with their symptoms and the dose of drugs taken. Results: Sixteen of the 28 patients increased their dose for asthma symptoms. The time to recovery from the asthma symptoms was significantly shorter when cough was the only symptom present compared with dyspnea or wheeze (1.4 vs. 5.3 or 6.6 days, p < 0.05) and when they had only one symptom compared with two or three symptoms (1.3 vs. 5.7 or 10.5, p < 0.01). The relationship between PEF (% of personal best) when the dose was increased (Y) and the days for the increased dose to achieve a PEF greater than PEF in the symptom-free state (X) was determined to be Y = - 0.591X + 89.2 (r2 = 0.299, p < 0.001). Conclusion: As a guide for increasing the BFC dose when patients with mild asthma have asthma symptoms, the dose should be increased when cough is present or PEF is decreased to 88.9% (i.e., X = 0.5). PMID- 29796289 TI - Clinical efficacy of teriflunomide over a fixed 2-year duration in the TOWER study. AB - Patients enrolled in the phase 3 TOWER study (NCT00751881) of teriflunomide had variable treatment durations (48-173 weeks). This has led to challenges when interpreting results in the context of other phase 3 trials of disease-modifying therapies for multiple sclerosis, which typically have a fixed 2-year duration. This communication reports clinical outcomes in TOWER over a fixed 2-year period. Reductions in annualised relapse rates and 12-week confirmed disability worsening associated with teriflunomide were comparable between overall intent-to-treat and fixed 2-year study populations in TOWER. Consistency in outcomes supports the inclusion of TOWER data in comparative analyses with other disease-modifying therapies. ClinicalTrials.gov: NCT00751881. PMID- 29796290 TI - Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study. AB - Background: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. Objective: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. Methods: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Results: Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. Conclusion: The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials. PMID- 29796291 TI - Daily rhythmicity in coastal microbial mats. AB - Cyanobacteria are major primary producers in coastal microbial mats and provide biochemical energy, organic carbon, and bound nitrogen to the mat community through oxygenic photosynthesis and dinitrogen fixation. In order to anticipate the specific requirements to optimize their metabolism and growth during a day and-night cycle, Cyanobacteria possess a unique molecular timing mechanism known as the circadian clock that is well-studied under laboratory conditions but little is known about its function in a natural complex community. Here, we investigated daily rhythmicity of gene expression in a coastal microbial mat community sampled at 6 time points during a 24-h period. In order to identify diel expressed genes, meta-transcriptome data was fitted to periodic functions. Out of 24,035 conserved gene transcript clusters, approximately 7% revealed a significant rhythmic expression pattern. These rhythmic genes were assigned to phototrophic micro-eukaryotes, Cyanobacteria but also to Proteobacteria and Bacteroidetes. Analysis of MG-RAST annotated genes and mRNA recruitment analysis of two cyanobacterial and three proteobacterial microbial mat members confirmed that homologs of the cyanobacterial circadian clock genes were also found in other bacterial members of the microbial mat community. These results suggest that various microbial mat members other than Cyanobacteria have their own molecular clock, which can be entrained by a cocktail of Zeitgebers such as light, temperature or metabolites from neighboring species. Hence, microbial mats can be compared to a complex organism consisting of multiple sub-systems that have to be entrained in a cooperative way such that the corpus functions optimally. PMID- 29796292 TI - A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study. AB - Background: Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to L120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. Methods: A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. Results: Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between L2234 (Cardiff) and L4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. Conclusions: We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR. PMID- 29796293 TI - Intensive therapy after botulinum toxin in adults with spasticity after stroke versus botulinum toxin alone or therapy alone: a pilot, feasibility randomized trial. AB - Background: Botulinum toxin-A is provided for adults with post-stroke spasticity. Following injection, there is a variation in the rehabilitation therapy type and amount provided. The purpose of this study was to determine if it is feasible to add intensive therapy to botulinum toxin-A injections for adults with spasticity and whether it is likely to be beneficial. Methods: Randomized trial with concealed allocation, assessor blinding, and intention to treat analysis. Thirty seven adults (n = 3 incomplete or lost follow-up) with spasticity in the upper or lower limb were allocated to one of three groups: experimental group received a single dose of botulinum toxin-A plus an intensive therapy for 8 weeks, control group 1 received a single dose of botulinum toxin-A only, and control group 2 received intensive therapy only for 8 weeks. Feasibility was measured by examining recruitment, intervention (adherence, acceptability, safety), and measurement. Benefit was measured as goal achievement (Goal Attainment Scale), upper limb activity (Box and Block Test), walking (6-min walk test) and spasticity (Tardieu scale), at baseline (week 0), immediately after (week 8), and at three months (week 12). Results: Overall recruitment fraction for the trial was 37% (eligibility fraction 39%, enrolment fraction 95%). The 26 participants allocated to receive intensive rehabilitation attended 97% of clinic-based sessions (mean 11 +/- 2 h) and an averaged 58% (mean 52 +/- 32 h) of prescribed 90 h of independent practice. There were no study-related adverse events reported. Although participants in all groups increased their goal attainment, there were no between-group differences for this or other outcomes at week 8 or 12. Conclusion: Providing intensive therapy following botulinum toxin-A is feasible for adults with neurological spasticity. The study methods are appropriate for a future trial. A future trial would require 134 participants to detect a between-group difference of 7 points on Goal Attainment Scale t-scores with an alpha of 0.05 and power of 80%. Trial registration: ACTRN12612000091808. Registered 18/01/2012, retrospective. PMID- 29796294 TI - Continuous, real-time monitoring of neonatal position and temperature during Kangaroo Mother Care using a wearable sensor: a techno-feasibility pilot study. AB - Background: Remote biomonitoring of vital parameters in hospitals and homes has the potential to improve coverage and quality of maternal and neonatal health. Wearable sensors coupled with modern information and communication technology now offer an opportunity to monitor temperatures and kangaroo mother care (KMC) adherence in a continuous and real-time manner remotely for several days' duration in hospital and home settings. Using an innovative remote biomonitoring device to measure both temperature and baby position, we undertook a techno feasibility study in preparation for a clinical trial. Methods: We designed and developed a wearable sensor for tracking KMC adherence and neonatal temperature, using social innovation design principles. After screening mother-infant dyads using clinical and logistic eligibility criteria, we piloted this wearable sensor along with a gateway device and the commercial cellular network. The dyads were recruited during hospitalization and followed up in the hospital and home phases for several days. Simple descriptive statistical analysis was undertaken. Results: Recruitment rate was 50% (6/12), and consenting rate was 83% (5/6) during a 2-month period. These five neonates contributed a total of 39 study days (15 hospital days and 24 home days). Their mean [+/- standard deviation (S.D.)] birth weight was 1490 (+/- 244) g.The mean (+/- S.D.) of the vital signs for the five babies was temperature [36.5 degrees C (+/- 0.3)], heart rate [146.5/min (+/- 14)], and oxygen saturation [94% (+/- 4)]. No severe or moderate side effects were noted; one baby developed mild dermatitis under the device that was transient and self-limiting, yielding an incidence proportion of 20% and incidence rate of 2.6/100 person-days.None of the mothers reported any discomfort with the use of the device. Temperatures detected from 81 paired readings revealed that those from the wearable sensor were 0.2 degrees C lower than those detected by clinical thermometers [36.4 (+/- 0.7) vs 36.6 (+/- 0.3); < 0.001].There was also iterative feedback that was useful for hardware and software design specifications of the wearable sensor, the gateway device, and the analytics platform. Lastly, lessons were learnt with regard to the logistics of research team interactions with healthcare professionals and study participants during the hospitalization and post-discharge home phases of the study. Conclusions: The pilot study has shown that it is feasible and acceptable to track KMC adherence as well as maternal and newborn temperatures in a potentially safe manner on a real-time mode for several days' duration during hospitalization and home phases. The pilot has also helped inform modifications in clinical monitoring, technological modifications, and logistics planning in preparation for the definitive clinical trial. Trial registration: Clinical Trials Registry of India, CTRI/2017/09/009789. PMID- 29796295 TI - Diagnostic and therapeutic yield of a patient-controlled portable EEG device with dry electrodes for home-monitoring neurological outpatients-rationale and protocol of the HOMEONE pilot study. AB - Background: The HOMEONE study is part of the larger HOME project, which aims to provide evidence of diagnostic and therapeutic yield ("change of management") of a patient-controlled portable EEG device with dry electrodes for the purposes of EEG home-monitoring neurological outpatients. Methods: The HOMEONE study is the first step in the process of investigating whether outpatient EEG home-monitoring changes the diagnosis and treatment of patients in comparison to conventional EEG ("change of management"). Both EEG devices (conventional and portable) will be systematically compared via a two-phase intra-individual assessment.In the first phase (pilot study phase), both EEG devices will be used within neurologist practices (all other things being equal). This pilot study (involving 130 patients) will evaluate the technical usability and efficacy of the new portable dry electrode EEG recorder in comparison to conventional EEG devices. Judgements will be based on technical assessments and EEG record examinations of private practitioners and two experienced neurologists (percent of concordant readings and kappa values).The second phase (feasibility study phase) aims to assess patients' acceptability and feasibility of the EEG home-monitoring and will provide insights into the extent diagnostic and therapeutic yields can be expected.For this purpose, a conventional EEG will be recorded in neurologist practices. Thereafter, the practice staff will instruct the patients on how the portable EEG device functions. The patients will subsequently use the devices in their home environment.The evaluation will compare the before and after documented diagnostic findings and the therapeutic consequences of the private practitioners with those of two experienced neurologists. Discussion: To the best of our knowledge, this will be the first study of its kind to examine new approaches to diagnosing unclear consciousness disorders or other disorders of the CNS or the cardiovascular system through the use of a patient-controlled portable EEG device with dry electrodes for the purpose of home-monitoring neurological outpatients. If the two phases of the HOMEONE study provide sufficient evidence of diagnostic and therapeutic yields, this would justify (indication-specific) full-scale randomized controlled trials or observational studies. Trial registration: DRKS DRKS00012685. Registered 9 August 2017, retrospectively registered. PMID- 29796296 TI - Prevalence and factors influencing modern contraceptive use among HIV-positive women in Kilimanjaro region, northern Tanzania. AB - Background: Mother-to-Child-Transmission (MTCT) of HIV is still a public health problem in sub-Saharan Africa. The region has a high unmet need for family planning and high unplanned pregnancy rates among HIV-positive women. Most efforts to prevent MTCT of HIV have focused on the third prong, a strategy which offers antiretroviral (ARV) drugs to HIV-infected pregnant women and their exposed infants. However, the effective use of contraceptives to prevent unplanned pregnancies among women living with HIV is more effective in reducing HIV MTCT. This study aimed at determining the prevalence and factors influencing modern contraceptive use among HIV-positive women in northern Tanzania. Methods: This was a cross-sectional study conducted between January and June 2014 in three selected districts of Kilimanjaro region, Tanzania. Data were collected during face-to-face interviews with HIV-positive women attending Care and Treatment Clinics (CTC) in the selected districts. Multivariate logistic regression analysis was used to determine independent predictors of modern contraceptive use. Results: In total 672 HIV-positive women were enrolled. Their mean age was 36.4 years (+/-7.7). Fifty four percent (362) were currently using modern contraceptives, and the most common method used was male condoms 76% (275) followed by Depo-Provera 28% (101). A total of 33% (121) of the users reported dual contraceptive use. Women with primary education [Adjusted Odds Ratio (AOR) = 7.54, 95% Confidence Interval (CI): 1.51-17.48, P = 0.014]; post-secondary [AOR = 6.23, 95% CI: 1.14-14.07, P = 0.035]; not currently on ARVs [AOR = 11.29, 95% CI: 2.60-19.94, P = 0.001]; currently sexually active [AOR = 8.40, 95% CI: 4.47 15.78, P < 0.001]; ever discussed contraceptive use with partner [AOR = 3.68, 95% CI: 1.67-8.11, P = 0.001]; and being counseled on dual contraceptive use at CTC [AOR = 2.94, 95% CI: 1.66-5.23, P < 0.001]; had significantly higher odds of currently using modern contraceptive methods. Conclusions: Given the population studied, the prevalence of modern contraceptive use was low. Strategies are required to increase the use of dual and long-term contraceptive methods among women who do not want more children in order to reduce MTCT, and to improve maternal and child health in the region. Programme managers and health care providers need to identify counseling strategies that are specific to HIV positive women that not only impart knowledge on contraceptives, but also address the issue of responsibility for influencing HIV transmission in the community. PMID- 29796297 TI - Genomic insights into nitrofurantoin resistance mechanisms and epidemiology in clinical Enterobacteriaceae. AB - Aim: Multidrug-resistant enterobacteria are highly associated with invasive devices and intensive care units. Increasing resistance to carbapenems is leading to the use of older and neglected antibiotics such as nitrofurantoin (NFT). The genomics of NFT resistance was investigated. Results & conclusion: High-level resistance to NFT (minimum inhibitory concentration >=128-512 mg/l) was recorded in 31/36 isolates (89.6%), many of which were from intensive care units (n = 20), urine (n = 17) or invasive procedures (n = 10). Efflux pump inhibitors had little effect on NFT's minimum inhibitory concentrations albeit oqxAB was prevalent in most isolates (n = 32). Various species- and clone-specific mutations mediating high-level NFT resistance were detected in nfsA, nfsB and ribE proteins through comparative genomics. Global phylogenomics showed local and independent emergence of NFT resistance in Enterobacteriaceae. NFT stewardship is advised. PMID- 29796298 TI - Gazing into smoldering volcanoes: precision cardiac imaging. PMID- 29796299 TI - Novel approaches to CMV after HCT: report from the 27th European Congress of Clinical Microbiology and Infectious Diseases, Vienna, Austria, 22-25 April 2017. PMID- 29796300 TI - Comparison of apixaban and rivaroxaban for anticoagulant effect after lumbar spine surgery: a single-center report. AB - Aim: To compare efficacy and safety of anticoagulants apixaban and rivaroxaban after lumbar spine surgery retrospectively. Methods: In this study comprising 480 patients, lower-limb swelling, deep venous thrombosis, pulmonary embolism, blood loss, ecchymosis and D-dimer changes were observed. Results: The changes in perimeter of the legs were tested, and significant differences were noted 10 cm above the patella, but no significant differences 10 cm below the patella. Twelve thrombotic events occurred in the apixaban group and nine in rivaroxaban group. No significant difference in the incidences of thromboembolic events (p = 1.00). Compared with rivaroxaban, there was significantly less bleeding in the apixaban group (p = 0.03). Conclusion: Apixaban and rivaroxaban were equally effective anticoagulation therapies that exhibited similar preventive effects against postoperative venous thromboembolism after lumbar spine surgery. PMID- 29796301 TI - Functional variants of TIM-3/HAVCR2 3'UTR in lymphoblastoid cell lines. AB - Aim: Variants of TIM-3/HAVCR2 3'UTR miRNA binding sites are significantly associated with cancer; however, roles in post-transcriptional regulation have not been elucidated. Methods: The regulatory and coding region single nucleotide polymorphisms (SNPs) of TIM-3/HAVCR2 were identified using an online database. Single nucleotide polymorphism Function Prediction was used to predict potential functional relevance of miRNA binding sites. Results: The analysis indicated rs9313439, rs4704846, rs3087616 and rs1036199 affect possible miRNA binding sites in TIM-3/HAVCR2 3'UTR. We used additional data on genotypes and limited minor allele frequency >5% in the HapMap populations. Only rs3087616 and rs4704846 were significantly associated with TIM-3/HAVCR2. Conclusion: Both rs3087616 and rs4704846 could be putative variants mediating post-transcriptional regulation of the TIM-3/HAVCR2. Deeper understanding of how 3'UTR variants influence the activity by TIM-3/HAVCR2 for therapy against cancer. PMID- 29796302 TI - Prospective single center trial of next-generation sequencing analysis in metastatic renal cell cancer: the MORE-TRIAL. AB - Aim: Targeted therapies have substantially improved the survival of patients with metastatic clear cell renal cell cancer. No prognostic or predictive biomarkers are available. Comprehensive genetic profiling offers the opportunity to define prognostic and predictive signatures aiming at a more personalized approach to treatment. Methods: In this prospectively conducted cohort study, tumor tissue and liquid biopsies are sampled at baseline and upon first and second progression under systemic treatment. Samples will be analyzed by whole-exome sequencing to generate prognostic and predictive patterns for systemic therapies. Discussion: This study is aiming at exploring genetic profiles with prognostic and predictive value in metastatic renal cell cancer patients. Clonal evolution facilitating resistance to systemic treatment will be investigated by repeat biopsies. PMID- 29796304 TI - Fully electronic urine dipstick probe for combinatorial detection of inflammatory biomarkers. AB - Aim: An electrochemical urine dipstick probe biosensor has been demonstrated using molybdenum electrodes on nanoporous polyamide substrate for the quantitative detection of two inflammatory protein biomarkers, CRP and IL-6. Materials & methods: The electrode interface was characterized using zeta potential and Fourier transform infrared spectroscopy. Detection of biomarkers was demonstrated by measuring impedance changes associated with the dose concentrations of the two biomarkers. A proof of feasibility of point-of-care implementation of the biosensor was demonstrated using a portable electronics platform. Results & conclusion: Limit of detection of 1 pg/ml was achieved for CRP and IL-6 in human urine and synthetic urine buffers. The developed portable hardware demonstrated close correlation with benchtop equipment results. PMID- 29796303 TI - Latest development on RNA-based drugs and vaccines. AB - Drugs and vaccines based on mRNA and RNA viruses show great potential and direct translation in the cytoplasm eliminates chromosomal integration. Limitations are associated with delivery and stability issues related to RNA degradation. Clinical trials on RNA-based drugs have been conducted in various disease areas. Likewise, RNA-based vaccines for viral infections and various cancers have been subjected to preclinical and clinical studies. RNA delivery and stability improvements include RNA structure modifications, targeting dendritic cells and employing self-amplifying RNA. Single-stranded RNA viruses possess self amplifying RNA, which can provide extreme RNA replication in the cytoplasm to support RNA-based drug and vaccine development. Although oligonucleotide-based approaches have demonstrated potential, the focus here is on mRNA- and RNA virus based methods. PMID- 29796305 TI - Prognostic significance of further axillary dissection in breast cancer patients with micrometastases & the number of micrometastases: a SEER population-based analysis. AB - Aim: To investigate the benefits of axillary dissection in patients with micrometastases. Methods: A review of data from the Surveillance, Epidemiology, and End Results database was performed from 2004 to 2013. Kaplan-Meier curves, Cox regression models, and propensity score matching were utilized to comprehensively evaluate the cohort. Results: Multivariate analysis after propensity score matching showed that patients with one to two micrometastases did not substantially benefit from axillary lymph node dissection in breast cancer-specific survival (p = 0.725). However, a subgroup analysis indicated that axillary dissection may benefit estrogen receptor-negative patients. Moreover, patients who carried three micrometastases had a significantly lower crude hazard ratio in breast cancer-specific survival. Conclusion: Axillary lymph node dissection may have advantages in high-risk micrometastatic patients. Patients with three micrometastases should be treated with caution. PMID- 29796307 TI - Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo. AB - Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5 diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening. PMID- 29796306 TI - Quantitative translational modeling to facilitate preclinical to clinical efficacy & toxicity translation in oncology. AB - Significant scientific advances in biomedical research have expanded our knowledge of the molecular basis of carcinogenesis, mechanisms of cancer growth, and the importance of the cancer immunity cycle. However, despite scientific advances in the understanding of cancer biology, the success rate of oncology drug development remains the lowest among all therapeutic areas. In this review, some of the key translational drug development objectives in oncology will be outlined. The literature evidence of how mathematical modeling could be used to build a unifying framework to answer these questions will be summarized with recommendations on the strategies for building such a mathematical framework to facilitate the prediction of clinical efficacy and toxicity of investigational antineoplastic agents. Together, the literature evidence suggests that a rigorous and unifying preclinical to clinical translational framework based on mathematical models is extremely valuable for making go/no-go decisions in preclinical development, and for planning early clinical studies. PMID- 29796308 TI - The prevalence of patient engagement in published trials: a systematic review. AB - Plain English summary: With the growing movement to engage patients in research, questions are being asked about who is engaging patients and how they are being engaged. Internationally, research groups are supporting and funding patient oriented research studies that engage patients in the identification of research priorities and the design, conduct and uptake of research. As we move forward, we need to know what meaningful patient engagement looks like, how it benefits research and clinical practice, and what are the barriers to patient engagement?We conducted a review of the published literature looking for trials that report engaging patients in the research. We included both randomized controlled trials and non-randomized comparative trials. We looked at these trials for important study characteristics, including how patients were engaged, to better understand the practices used in trials. Importantly, we also discuss the number of trials reporting patient engagement practices relative to all published trials. We found that very few trials report any patient engagement activities even though it is widely supported by many major funding organizations. The findings of our work will advance patient-oriented research by showing how patients can be engaged and by stressing that patient engagement practices need to be better reported. Abstract: Background: Patient-Oriented Research (POR) is research informed by patients and is centred on what is of importance to them. A fundamental component of POR is that patients are included as an integral part of the research process from conception to dissemination and implementation, and by extension, across the research continuum from basic research to pragmatic trials [J Comp Eff Res 2012, 1:181-94, JAMA 2012, 307:1587 8]. Since POR's inception, questions have been raised as to how best to achieve this goal.We conducted a systematic review of randomized controlled trials and non-randomized comparative trials that report engaging patients in their research. Our main goal was to describe the characteristics of published trials engaging patients in research, and to identify the extent of patient engagement activities reported in these trials. Methods: The MEDLINE(r), EMBASE(r), Cinahl, PsycINFO, Cochrane Methodology Registry, and Pubmed were searched from May 2011 to June 16th, 2016. Title, abstract and full text screening of all reports were conducted independently by two reviewers. Data were extracted from included trials by one reviewer and verified by a second. All trials that report patient engagement for the purposes of research were included. Results: Of the 9490 citations retrieved, 2777 were reviewed at full text, of which 23 trials were included. Out of the 23 trials, 17 were randomized control trials, and six were non-randomized comparative trials. The majority of these trials (83%, 19/23) originated in the United States and United Kingdom. The trials engaged a range of 2-24 patients/ community representatives per study. Engagement of children and minorities occurred in 13% (3/23) and 26% (6/23) of trials; respectively. Engagement was identified in the development of the research question, the selection of study outcomes, and the dissemination and implementation of results. Conclusions: The prevalence of patient engagement in patient-oriented interventional research is very poor with 23 trials reporting activities engaging patients. Research dedicated to determining the best practice for meaningful engagement is still needed, but adequate reporting measures also need to be defined. PMID- 29796309 TI - Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury. AB - Vascular endothelial cadherin (VE-cad) expression at endothelial adherens junctions (AJs) regulates vascular homeostasis. Here we show that endothelial A20 is required for VE-cad expression at AJs to maintain and repair the injured endothelial barrier. In endothelial cell (EC)-restricted Tnfaip3 (A20) knockout (A20?EC ) mice, LPS challenge caused uncontrolled lung vascular leak and persistent sequestration of polymorphonuclear neutrophil (PMNs). Importantly, A20?EC mice exhibited drastically reduced VE-cad expression in lungs compared with wild-type counterparts. Endothelial expression of wild-type A20 but not the deubiquitinase-inactive A20 mutant (A20C103A) prevented VE-cad ubiquitination, restored VE-cad expression, and suppressed lung vascular leak in A20?EC mice. Interestingly, IRAK-M-mediated nuclear factor-kappaB (NF-kappaB) signaling downstream of TLR4 was required for A20 expression in ECs. interleukin-1 receptor associated kinase M (IRAK-M) knockdown suppressed basal and LPS-induced A20 expression in ECs. Further, in vivo silencing of IRAK-M in mouse lung vascular ECs through the CRISPR-Cas9 system prevented expression of A20 and VE-cad while augmenting lung vascular leak. These results suggest that targeting of endothelial A20 is a potential therapeutic strategy to restore endothelial barrier integrity in the setting of acute lung injury. PMID- 29796310 TI - Immune system correlates of extensive limb swelling in response to conjugated pneumococcal vaccination. AB - Pneumococcal conjugate vaccine (PCV) is recommended for adults with chronic disease. Extensive limb swelling (ELS) is an acute vigorous local inflammatory reaction following vaccination. Predisposing immune system correlates and the influence of ELS on vaccine responses are not known. Here, we report a case of a 67-year-old woman with a history of multiple pneumonias who had a detailed immunological work-up pre-vaccination because of suspected immunodeficiency. Four days following a first vaccination with PCV13 she developed ELS-mimicking erysipelas. Treatment with 20 mg cortisone completely alleviated symptoms within 2 days. Skin biopsy showed a dense dermal and subdermal infiltration dominated by CD4+ T cells and macrophages. In a multiplexed serotype-specific measurement of the anti-pneumococcal IgG response, the patient showed very broad and strong vaccine responses. Pre-vaccination titers were low for the vaccine serotypes. We did not find in vivo nor in vitro evidence of an excessive T cell response to the diphtheria-derived PCV carrier protein. However, we could demonstrate a high antibody titer to a non-vaccine serotype, indicating in vivo pre-exposure to pneumococcus bacteria. Thus, traces of pneumococcal proteins included in PCV13 may have boosted pre-existing pneumococcus-specific T helper cells, which subsequently orchestrated ELS. Our case raises awareness for the risk of vaccine induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity. PMID- 29796311 TI - Role of Direct Antiviral Agents in Treatment of Chronic Hepatitis C Infection in Renal Transplant Recipients. AB - Background: Since the introduction of direct antiviral agents (DAAs), morbidity of HCV has considerably decreased but still no guidelines have been formulated in renal transplant recipients (RTRs). We studied efficacy and tolerability of direct antiviral agents in RTRs. Methods: This prospective observational study was conducted at Army Hospital Research & Referral, Delhi, from June 2016 to May 2017. Forty-five HCV infected RTRs with stable graft function were included. Results: Median time between renal transplantation and the start of anti-HCV therapy was 36 months (1-120 months). The majority (66.7%) were infected with genotype 3. Baseline median HCV RNA level was 542648 IU/ml (1189-55028534 IU/ml). Sofosbuvir-Ribavirin combination (24 weeks) was given to 30 patients including 3 cirrhotics, Ledipasvir-Sofosbuvir combination to 8 patients, and Daclatasvir Sofosbuvir combination to 7 patients, including 2 cirrhotics. Rapid virological response was observed in 29 patients treated with Sofosbuvir/Ribavirin, all 8 patients on Sofosbuvir/Ledipasvir, and all 7 patients on Sofosbuvir/Daclatasvir. End treatment response and sustained virological response (12 weeks) were achieved in all patients irrespective of genotype or treatment regimen. Decrease in mean HCV RNA level and transaminase level was statistically significant (p < 0.01). Ribavirin was significantly associated with anaemia (p = 0.032). Conclusions: DAA regimens are well tolerated and highly efficacious. Response to DAA is good irrespective of genotype, drug combination, initial HCV RNA level, age or sex of patient, or graft age. However, Sofosbuvir/Ledipasvir and Sofosbuvir/Daclatasvir combination is preferable. PMID- 29796312 TI - Granulosa Cell Tumor of the Ovary: A Retrospective Study of 31 Cases and a Review of the Literature. AB - Background: Adult granulosa cell tumors (AGCTs) are the most common sex cord stromal tumors. Unlike epithelial ovarian tumors, they occur in young women and are usually detected at an early stage. The aim of this study was to report the clinical and pathological characteristics of AGCT patients and to identify the prognostic factors. Methods: All cases of AGCTs, treated at Salah Azaiz Institute between 1995 and 2010, were retrospectively included. Kaplan-Meier's statistical method was used to assess the relapse-free survival and the overall survival. Results: The final cohort included 31 patients with AGCT. The mean age was 53 years (35-73 years). Patients mainly presented with abdominal mass and/or pain (61%, n = 19). Mean tumor size was 20 cm. The majority of patients had a stage I disease (61%, n = 19). Two among 3 patients with stage IV disease had liver metastasis. Mitotic index was low in 45% of cases (n = 14). Surgical treatment was optimal in almost all cases (90%, n = 28). The median follow-up time was 14 years (1-184 months). Ten patients relapsed (32%) with a median RFS of 8.4 years (6.8-9.9 years). Mean overall survival was 13 years (11-15 years). Stage I disease and low-to-intermediate mitotic index were associated with a better prognosis in univariate analysis (resp., p = 0.05 and p = 0.02) but were not independent prognostic factors. Conclusion: GCTs have a long natural history with common late relapses. Hence, long active follow-up is recommended. In Tunisian patients, hepatic metastases were more frequent than occidental series. The prognosis remains good and initial staging at diagnosis is an important prognostic factor. PMID- 29796314 TI - Clinical Features of Idiopathic Parotid Pain Triggered by the First Bite in Japanese Patients with Type 2 Diabetes: A Case Study of Nine Patients. AB - Objective: First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. Study Design: A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. Results: All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0-10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1-10 min after meals in six patients. Conclusions: IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different. PMID- 29796313 TI - Microvascular Anastomosis Training in Neurosurgery: A Review. AB - Cerebrovascular diseases are among the most widespread diseases in the world, which largely determine the structure of morbidity and mortality rates. Microvascular anastomosis techniques are important for revascularization surgeries on brachiocephalic and carotid arteries and complex cerebral aneurysms and even during resection of brain tumors that obstruct major cerebral arteries. Training in microvascular surgery became even more difficult with less case exposure and growth of the use of endovascular techniques. In this text we will briefly discuss the history of microvascular surgery, review current literature on simulation models with the emphasis on their merits and shortcomings, and describe the views and opinions on the future of the microvascular training in neurosurgery. In "dry" microsurgical training, various models created from artificial materials that simulate biological tissues are used. The next stage in training more experienced surgeons is to work with nonliving tissue models. Microvascular training using live models is considered to be the most relevant due to presence of the blood flow. Training on laboratory animals has high indicators of face and constructive validity. One of the future directions in the development of microsurgical techniques is the use of robotic systems. Robotic systems may play a role in teaching future generations of microsurgeons. Modern technologies allow access to highly accurate learning environments that are extremely similar to real environment. Additionally, assessment of microsurgical skills should become a fundamental part of the current evaluation of competence within a microneurosurgical training program. Such an assessment tool could be utilized to ensure a constant level of surgical competence within the recertification process. It is important that this evaluation be based on validated models. PMID- 29796315 TI - The Influence of Video Game Training with and without Subpatelar Bandage in Mobility and Gait Speed on Elderly Female Fallers. AB - Objectives: The aim of the study was to investigate the effect of balance training with Nintendo Wii technology, with and without the use of additional sensory information (subpatellar bandage), in the functional mobility and gait speed of elderly female fallers. Methods: Twenty elderly women were divided into two groups: group I: trained with the use of the Nintendo Wii; group II: trained using the Nintendo Wii and the addition of sensory information (subpatellar bandage). The functional mobility was assessed with the Timed up and Go test (TUG) and gait speed with the 10 m test. The tests were carried out with and without the use of the subpatellar bandage. The training was carried out within sessions of 30 minutes, twice a week, using three different games (Penguin Slide, Table Tilt, and Tightrope). Results: There was an increase in the gait speed and a decrease in the TUG time in both groups, independently of the sensory condition used (p < 0.05). In the short term, the subpatellar bandage improved the TUG time (p < 0.05) and the gait speed (p < 0.01). Conclusion: The training for postural balance with virtual reality was effective for improving functional mobility and gait speed of elderly female fallers. The subpatellar bandage did not maximize the effect of training. PMID- 29796317 TI - Anesthetic Implications for Cesarean Section in a Parturient with Complex Congenital Cyanotic Heart Disease. AB - The discordance between increased physiological demand during pregnancy and congenital cardiac pathology of a parturient is a perilous threat to the maternal fetal well-being. Early involvement of a multidisciplinary team is essential in improving peripartum morbidity and mortality. Designing the most appropriate anesthetic care will require a concerted effort, with inputs from the obstetricians, obstetric and cardiac anesthesiologists, cardiologists, neonatologists, and cardiothoracic surgeons. We report the multidisciplinary peripartum care and anesthetic management for cesarean section (CS) of a 28-year old primigravida who has partially corrected transposition of the great arteries, atrial and ventricular septal defect, dextrocardia, right ventricle hypoplasia, and tricuspid atresia. PMID- 29796316 TI - Effect of N-Acetylcysteine on Dyslipidemia and Carbohydrate Metabolism in STZ Induced Diabetic Rats. AB - Background: Type 1 diabetes mellitus (T1DM) is characterized by insulin-deficient production leading to hyperglycemia, which is associated with diabetic complications such as cardiovascular diseases. Antioxidants have been proving a good alternative to diabetic complications, with N-acetylcysteine (NAC) having antioxidant characteristics. The aim of this study was to assess the effect of NAC on the lipid profile and the atherogenic index (AI) in streptozotocin- (STZ-) induced diabetic rats. Method: 32 male Wistar rats (60 days of age) weighting +/ 250 g were randomly distributed into four groups (n = 8): CTRL: control rats; CTRL+NAC: control rats treated with NAC; DM: diabetic rats; DM+NAC: diabetic rats treated with NAC. T1DM was induced using STZ (60 mg/kg, ip; single dose), and NAC (25 mg/kg/day) was administrated by gavage, for 37 days. The animals received chow and water ad libitum. After the experimental period, blood and cardiac tissue samples were collected to analyze energetic metabolism, lipid profile, and AI. Results: NAC decreased (p < 0.01) glycemia, energy intake, carbohydrate, and protein consumption in diabetic rats (DM+NAC), when compared with DM, while the alimentary efficiency was improved (p < 0.01) in treated diabetic rats (DM+NAC). Diabetic rats treated with NAC decreased (p < 0.01) lipid profile and AI in diabetic rats (DM+NAC) when compared to DM. Conclusion: NAC improves lipid profile and decreases AI in STZ-induced diabetic rats. PMID- 29796318 TI - Transcatheter Aortic Valve Replacement Incidentalomas: A Multimodality Imaging Case of Giant Right Coronary Aneurysm. AB - Giant coronary artery aneurysms (CAAs) are defined as having a diameter of greater than 2 cm. We report a case of an 82-year-old male with severe aortic stenosis incidentally diagnosed with giant right coronary artery aneurysm (gRCAA) while undergoing evaluation for transcather aortic valve replacement (TAVR). It was causing a mass effect on the right cardiac chambers but was otherwise asymptomatic. Our patient was successfully treated with surgical excision of aneurysm with concomitant coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR). The patient remained stable at discharge and on serial follow-ups for two years. In conclusion, due to the associated complication and increased risk of mortality with giant coronary aneurysms, we recommend surgical approach instead of medical management alone. We also call for evidence-based recommendations and guidelines for management of TAVR incidentalomas. PMID- 29796319 TI - Fifteen-Year Follow-Up of a Case of Surgical Retreatment of a Single Gingival Recession. AB - Purpose: The aim of the present case report was to describe the retreatment of the single gingival recession in aesthetic area, in the presence of scar formation and consequent impairment of aesthetic appearance. Methods: A young patient with one single recession of 4 mm of 2.1 was treated with coronally advanced flap and subepithelial connective tissue graft, through a microsurgical approach that aimed at the removal of the scarred fibrous tissue. The intervention was performed using a surgical microscope as a magnification device. Results: Fifteen years after the surgical treatment, a substantial stable resolution of the gingival recession could be observed. Moreover, a further improvement of the aesthetic appearance could be observed. Conclusions: This case report suggests that periodontal microsurgery could be an effective approach for the retreatment of gingival recessions and, in long-term evaluation, to reduce the aesthetic problem due to the presence of scar formation. Further studies with a larger sample size are needed to better evaluate its efficacy. PMID- 29796320 TI - Clinical and Radiographic Success of Selective Caries Removal to Firm Dentin in Primary Teeth: 18-Month Follow-Up. AB - The selective caries removal is increasingly spreading in daily clinical practice because this minimally invasive technique treats deep carious lesion and decreases the risk of pulp exposure. This case report was aimed at describing the selective removal to firm dentin on the primary mandibular left first molar of a girl aged 7 years and 6 months. The Mineral Trioxide Aggregate (MTA AngelusTM) was used as liner, and the tooth was definitively restored with resin-modified glass ionomer cement (VitremerTM). The clinical and radiographic following-up was performed at 6, 12, and 18 months after treatment. The treatment showed satisfactory results after 18-month following-up, suggesting that this minimally invasive approach for carious lesion removal can replace the total removal, when properly indicated. Notwithstanding, further randomized clinical trials with longer following-up periods are still necessary. PMID- 29796321 TI - Mistaken Diabetic Ulcers: A Case of Bilateral Foot Verrucous Carcinoma. AB - Verrucous carcinoma (VC) is a rare, low-grade, and well-differentiated variant of squamous cell carcinoma. These tumors are slow-growing and exophytic and have a negligible incidence of metastasis. Treatment is complete surgical resection, ideally by Mohs micrographic surgery, to ensure adequate clear margins. Cutaneous VC predominantly occurs on the plantar surface of the foot and rarely occurs in multiple sites. This case study describes the fourth reported occurrence of bilateral VC of the feet in a woman with chronic diabetic foot ulcers. The case provides further support for persistent wounds contributing to the development of this lesion and describes their role in the characteristic delay in diagnosis of VC. PMID- 29796322 TI - A Supernumerary Nipple-Like Clinical Presentation of Lymphangioma Circumscriptum. AB - Lymphangioma circumscriptum is a superficially localized variant of lymphangioma. The characteristic clinical presentation is a "frogspawn" grouping of vesicles or papulovesicles on the proximal limb or limb girdle areas. Though most lymphangiomas develop congenitally, the lymphangioma circumscriptum subtype is known to present in adults. We report a case of lymphangioma circumscriptum on the left inframammary area of an African American female with an unusual supernumerary nipple-like clinical presentation. Our patient presented with a firm, smooth, hypopigmented papule, and the clinical diagnosis of keloid was made initially. However, she returned reporting growth of the lesion and was noted to have a firm, exophytic, lobulated, pink to skin-colored nodule. Histopathological examination demonstrated dilated lymphatic vessels, consistent with the diagnosis of lymphangioma. The presentation as a firm, hypopigmented papule and later exophytic, lobulated, skin-colored nodule in our case represents a clinical presentation of lymphangioma circumscriptum not previously described in the literature. Correct diagnosis in lymphangioma circumscriptum is vital, as recurrence following surgical resection and secondary development of lymphangiosarcoma and squamous cell carcinoma following treatment with radiation have been reported. Thus, it is important to consider lymphangioma circumscriptum in the differential of similar lesions in the future to allow appropriate diagnosis, treatment, and monitoring. PMID- 29796323 TI - Identification of a Novel Mutation in a Family with Pseudohypoparathyroidism Type 1a. AB - Introduction: Pseudohypoparathyroidism type 1a is caused by GNAS mutations leading to target organ resistance to multiple hormones rather than parathyroid hormone, resulting not only in hypocalcemia, but also in Albright's hereditary osteodystrophy phenotype. Materials and Methods: DNA sequencing of the GNAS gene identified a novel heterozygous mutation in peripheral blood leukocytes in the family presented in this case report. Results: We present a case of a 25-year-old woman with pseudohypoparathyroidism type 1a admitted with seizures, whose family presents an autosomal dominant transmission of a novel heterozygous GNAS mutation (c.524_530+3del). Conclusion: Pseudohypoparathyroidism type 1a is mostly caused by inactivating GNAS mutations that have been gradually reported in the literature that lead to a typical and complex clinical phenotype and resistance to multiple hormones. The deletion caused by the mutation identified in the presented case has not been reported previously. PMID- 29796324 TI - A Case of Pneumothorax after Treatment with Lenvatinib for Anaplastic Thyroid Cancer with Lung Metastasis. AB - A 63-year-old man was diagnosed with multiple lung metastases from anaplastic thyroid cancer and received lenvatinib. Follow-up computed tomography on day 34 of lenvatinib treatment showed pneumothorax. The pneumothorax was temporarily improved with chest drainage. However, pleurodesis was performed to treat a relapse of the pneumothorax. Pneumothorax during chemotherapy for a malignant tumor is considered a relatively rare complication. This case is the first documentation that pneumothorax may develop during lenvatinib treatment. The possible development of pneumothorax should be considered when lenvatinib is used in patients with lung metastasis. PMID- 29796325 TI - Patient with Marfan Syndrome and a Novel Variant in FBN1 Presenting with Bilateral Popliteal Artery Aneurysm. AB - We present a 43-year-old man with aortic root dilation, mitral valve prolapse, and marfanoid appearance, who presented with acute onset left leg pain. He underwent a Doppler ultrasound that revealed left popliteal artery aneurysm with thrombus. CT angiogram showed bilateral popliteal artery aneurysms. After repairing of his left popliteal artery aneurysm, he was sent for genetic evaluation. He was diagnosed with Marfan syndrome (MFS) based on the revised Ghent criteria and then underwent FBN1 sequencing and deletion/duplication analysis, which detected a novel pathogenic variant in gene FBN1, denoted by c.5872 T>A (p.Cys1958Ser). MFS is a connective tissue disorder with an autosomal dominant inheritance due to pathogenic variants in FBN1 that encodes Fibrillin-1, a major element of the extracellular matrix, and connective tissue throughout the body. MFS involves multiple systems, most commonly the cardiovascular, musculoskeletal, and visual systems. In our case we present a rare finding of bilateral popliteal artery aneurysms in a male patient with MFS. PMID- 29796326 TI - Castleman's Disease and Posttransplant Lymphoproliferative Disorder after Liver Transplant: 3-Year Follow-Up. AB - A 59-year-old male with a history of hepatitis C cirrhosis and history of hepatitis B exposure presented 8 months after orthotopic liver transplant (LT) with fever, fatigue, myalgia, night sweats, nonproductive cough, and shortness of breath. Bone marrow biopsy for pancytopenia was positive for Epstein-Barr virus (EBV) DNA. Lymph node biopsy for lymphadenopathy on imaging showed human herpes virus 8 (HHV8) associated Castleman's disease. Treatment included valganciclovir, rituximab, and prednisone taper with eventual discontinuation. Quantitative HHV8 DNA was initially 611,000 DNA copies/mL and was later undetectable at 6 months following treatment and remained undetectable at 3-year follow-up. PMID- 29796327 TI - Effective Immunotherapy in Bone Marrow Metastatic Melanoma Presenting with Disseminated Intravascular Coagulopathy. AB - Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature. PMID- 29796328 TI - Upper Extremity Compartment Syndrome in a Patient with Acute Gout Attack but without Trauma or Other Typical Causes. AB - We report the case of a 30-year-old Polynesian male with a severe gout flare of multiple joints and simultaneous acute compartment syndrome (ACS) of his right forearm and hand without trauma or other typical causes. He had a long history of gout flares, but none were known to be associated with compartment syndrome. He also had concurrent infections in his right elbow joint and olecranon bursa. A few days prior to this episode of ACS, high pain and swelling occurred in his right upper extremity after a minimal workout with light weights. A similar episode occurred seven months prior and was attributed to a gout flare. Unlike past flares that resolved with colchicine and/or anti-inflammatory medications, his current upper extremity pain/swelling worsened and became severe. Hand and forearm fasciotomies were performed. Workup included general medicine, rheumatology and infectious disease consultations, myriad blood tests, and imaging studies including Doppler ultrasound and CT angiography. Additional clinical history suggested that he had previously unrecognized recurrent exertional compartment syndrome that led to the episode of ACS reported here. Chronic exertional compartment syndrome (CECS) presents a difficult diagnosis when presented with multiple symptoms concurrently. This case provides an example of one such diagnosis. PMID- 29796329 TI - Ectopic Intratracheal Thyroid: A Rare Cause of Airway Obstruction. AB - Ectopic intratracheal thyroid tissue (EITT) is a rare abnormality with only limited cases reported so far. The presenting symptoms can be very similar to those of bronchial asthma. We discuss the case of a 29-year-old man with subglottic ectopic thyroid, with a history of thyroid surgery for goiter, which has been managed with laser-assisted endoscopic approach. We have also included presenting symptoms, pathophysiology, diagnosis, and management of EITT. We aim to include EITT in the differentials of airway obstruction, particularly in those patients who have goiter or previous thyroid surgeries. PMID- 29796330 TI - Combined Surgical Approach for Obstructive Sleep Apnea Patient. AB - Obstructive sleep apnea (OSA) is a disease that is associated with high morbidity and mortality and can significantly impact the quality of life in a patient. OSA is strongly associated with obesity, and literature showed that weight loss will lead to improvement in OSA. The gold standard treatment for OSA is continuous positive airway pressure (CPAP). However, other methods of treatment are available. One of these methods is multilevel sleep surgery (MLS). Literature showed that bariatric surgery can also improve OSA. A common question is which surgical procedure of these two should be performed first. We present a 5-year follow-up of a patient who underwent simultaneously bariatric surgery and MLS. His apnea-hypopnea index (AHI) decreased from 53 episodes per hour to 5.2 per hour within the first 18 months, which was measured via a level 3 polysomnography. Five years after the surgery, a repeat level 3 polysomnography showed an AHI of 6.8 episodes per hour, and the patient is asymptomatic. The patient maintained his weight and did not use CPAP after the combined surgery during the five-year period. PMID- 29796331 TI - A Rare Incidental Finding of a Foreign Body in the Nasopharynx during Adenotonsillectomy. AB - Diverse foreign bodies may become lodged in the aerodigestive tract, and the discovery of such foreign bodies is an expected scenario for health-care practitioners. The foreign body insertion may be accidental or deliberate, and the object may be organic or inorganic. Most accidental foreign body aspirations occur in children, and some such cases are potential threats that go unnoticed. Very few cases of foreign bodies in the nasopharynx have been reported. Herein, we describe an unusual case in which a foreign body in a child's nasopharynx went unnoticed for 1 year and was detected intraoperatively. PMID- 29796332 TI - Ileocecal Fistula Caused by Multiple Foreign Magnetic Bodies Ingestion. AB - The incidence of accidental foreign body (FBs) ingestion is 100,000 cases/year in the US, with over than 80% of cases occurring in children below 5 years of age. Although a single FB may pass spontaneously and uneventfully through the digestive tract, the ingestion of multiple magnetics can cause serious morbidity due to proximate attraction through the intestinal wall. Morbidity and mortality depend on a prompt and correct diagnosis which is often difficult and delayed due to the patient's age and because the accidental ingestion may go unnoticed. We report our experience in the treatment of an 11-year-old child who presented to the emergency department with increasing abdominal pain, vomiting, diarrhea, and fever. Surgery evidenced an ileocecal fistula secondary to multiple magnetic FB ingestion with attraction by both sides of the intestinal wall. A 5-centimeter ileal resection was performed, and the cecal fistula was closed with a longitudinal manual suture. The child was discharged at postoperative day 8. After one year, the patient's clinical condition was good. PMID- 29796333 TI - Transanal Drainage of Coloanal Anastomotic Leaks. AB - The conventional operative intervention for leaks following coloanal anastomoses has been proximal fecal diversion with or without take-down of anastomosis. A few of these cases are also amenable to percutaneous drainage. Ostomies created in this situation are often permanent, specifically in cases where coloanal anastomoses are taken down at the time of reoperation. We present two patients who developed perianastomotic pelvic abscesses that were treated with transanal large bore catheter drainage resulting in successful salvage of coloanal anastomoses without the need for a laparotomy or ostomy creation. We propose this to be an effective therapeutic approach to leaks involving low coloanal anastomoses in the absence of generalized peritonitis. PMID- 29796334 TI - The Effect of Comorbidities and Age on Functional Outcomes After Total Knee Arthroplasty in the Octogenarian: A Matched Cohort Study. AB - Introduction: According to the World Health Organization data repository, the average life expectancy at birth for Singapore in 2015 has risen to 83.4 years, and many octogenarians (OG) remain active socioeconomically. The aim of this study is to compare the improvement and the impact of comorbidities on functional recovery after total knee arthroplasty (TKA) between OG and their younger counterparts. Methods: This is a retrospective study of prospectively collected data from a single institution arthroplasty register. Between January 2006 and December 2011, 209 OG with primary knee osteoarthritis underwent TKA. Each OG (mean age 82 +/- 2.1) was then carefully matched to a younger control group (YG, mean age 66 +/- 4.5). Their postoperative outcomes measured include Oxford Knee Score (OKS), SF36-Physical Function (SF-PF), and knee society rating score comprising of Knee Score (KS) and Function Score (FS). Their respective degrees of improvement were compared and adjusted for their baseline comorbidities, measured using the Deyo-Charlson Comorbidity Index (D-CCI). Results: There were more comorbidities among the OG (P < .05). Both groups saw the largest improvement (P < .05) during the first 6 months. There was no statistical significance between their improvement for OKS, KS, and FS between baseline and 6 months and OKS, FS, and SF-PF between 6 and 24 months. Adjusted for D-CCI using linear regression, the above results remained largely unchanged. Discussion: In our study, both groups showed significant improvement across all functional outcomes, especially during the first 6 months. The improvement observed in OG at 6 and 24 months was comparable to that of YG, despite an overall higher baseline D-CCI. Conclusions: Total knee arthroplasty is a viable treatment option for the OG, offering good functional outcomes and results at 6 and 24 months when compared to their younger counterparts. PMID- 29796335 TI - TALEN-Mediated FLAG-Tagging of Endogenous Histone Methyltransferase DOT1L. AB - Histone modification including H3 lysine 79 methylation (H3K79me) plays a key role during gene transcription and DNA damage repair. DOT1L, the sole methyltransferase for three states of H3K79me, is implicated in leukemia, co lorectal cancer, and dilated cardiomyopathy. However, understanding of DOT1L and H3K79me in these pathways and disease pathogenesis has been limited due to the difficulty of working with DOT1L protein. For instance, locus-specific or genome wide binding sites of DOT1L revealed by chromatin immunoprecipitation (ChIP) based methods are necessary for inferring its functions, but high-quality ChIP grade antibodies are currently not available. Herein we have developed a knock-in approach to tag endogenous DOT1L with 3 * Flag at its C-terminal domain to follow functional analyses. The knock-in was facilitated by using TALENs to induce a targeted double-strand break at the endogenous DOTIL to stimulate local homologous recombination at that site. The single cell colonies with successful knock-in were isolated and verified by different methods. We also demonstrated that tagged DOT1L maintains its normal function in terms of methylation and that the engineered cells would be very useful for further studies. PMID- 29796336 TI - Fair Inference on Outcomes. AB - In this paper, we consider the problem of fair statistical inference involving outcome variables. Examples include classification and regression problems, and estimating treatment effects in randomized trials or observational data. The issue of fairness arises in such problems where some covariates or treatments are "sensitive," in the sense of having potential of creating discrimination. In this paper, we argue that the presence of discrimination can be formalized in a sensible way as the presence of an effect of a sensitive covariate on the outcome along certain causal pathways, a view which generalizes (Pearl 2009). A fair outcome model can then be learned by solving a constrained optimization problem. We discuss a number of complications that arise in classical statistical inference due to this view and provide workarounds based on recent work in causal and semi-parametric inference. PMID- 29796337 TI - Understanding metabolic changes in aging bone marrow. AB - Background: Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. Methods: In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis. Results: The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low beta-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of 'metabolic aging' with chemotherapy exposure. Conclusion: Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow. PMID- 29796338 TI - Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial. AB - Objectives: To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Design: Two-arm, wait-list controlled RCT. Settings: Tertiary care hospital. Subjects: Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. Interventions: Six-month TC intervention added to usual care (UC) versus UC alone. Outcome Measures: Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Results: Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conclusions: Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD. PMID- 29796339 TI - Evaluation of Cytotoxic and Genotoxic Effects of Extremely Low-frequency Electromagnetic Field on Mesenchymal Stromal Cells. AB - Background: Interest in the use of extremely low-frequency (ELF) electromagnetic field (EMF) for the treatment of pain and inflammation is increasing due to the ability of this promising therapy to compete with pharmaceuticals without the adverse effects caused by drugs. However, there continues to be concerns regarding cytotoxic and genotoxic effects that may occur as a result of exposure to EMF. Objective: To investigate this concern, we tested the effect of our known therapeutic 5 Hz, 0.4 milliTesla (mT) EMF on a human mesenchymal stromal cell (hMSC) line to determine whether ELF-EMF exposure would cause cytotoxic or genotoxic effects. Methods: Treated samples along with controls were exposed to 5 Hz, 0.4 mT ELF-EMF for 20 min/day, 3*/week for 2 weeks and then assayed for cell viability, proliferation rates, and chromosome breaks. Results: Cytogenetic analysis of the viability and proliferation rates along with analysis of morphological genome stability showed no cytotoxicity, and no chromosome breaks per karyotype analysis-therefore no genotoxicity. Conclusion: Exposure to an ELF EMF of 5 Hz, 0.4 mT for 20 min/day, 3*/week for 2 weeks does not cause cytotoxic or genotoxic effects in hMSCs. PMID- 29796340 TI - The Independent Specialty Medical Advocate Model of Patient Navigation and Intermediate Health Outcomes in Newly Diagnosed Cancer Patients. AB - Background: Navigation programs are generally characterized as providing patient centered support and guidance intended to help patients and family members overcome barriers such as timely diagnosis resolution, patient satisfaction, coping with primary and adjuvant treatment, management of side effects, and patient engagement in the healthcare process. The aim of this study was to examine the associations between the Independent Specialty Medical Advocate (ISMA) model of patient navigation and intermediate patient health outcomes for newly diagnosed cancer patients. Methods: A pre-post intervention study was conducted in 26 newly diagnosed cancer patients recruited from a national partnership between the LIVESTRONG Cancer Navigation Service Program and the NavigateCancer Foundation between April 2013 and December 2015. Participants received a 1-hour initial telephone consultation, and then a navigation care plan was developed for the 6-week study period. A paired t test was conducted to assess changes in intermediate health outcomes at baseline and 6 weeks after study intervention. Results: The majority of study participants were males (62%), married (50%), and Caucasian (69%). Overall, there was a statistically significant reduction in anxiety at 6 weeks postintervention (mean, 2.48; SD, 0.62; P <.05) compared with baseline (mean, 2.92; SD, 0.82) and in depression at 6 weeks postintervention (mean, 2.00; SD, 0.81; P <.05) compared with baseline (mean, 2.45; SD, 0.19). Conclusion: The ISMA model of patient navigation appears to be associated with significant reduction in anxiety and depression. Further studies are needed to evaluate the ISMA model of patient navigation on long-term patient outcomes. PMID- 29796341 TI - Tetrapod tracks in Permo-Triassic eolian beds of southern Brazil (Parana Basin). AB - Tetrapod tracks in eolianites are widespread in the fossil record since the late Paleozoic. Among these ichnofaunas, the ichnogenus Chelichnus is the most representative of the Permian tetrapod ichnological record of eolian deposits of Europe, North America and South America, where the Chelichnus Ichnofacies often occurs. In this contribution, we describe five sets of tracks (one of which is preserved in cross-section), representing the first occurrence of Dicynodontipus and Chelichnus in the "Piramboia Formation" of southern Brazil. This unit represents a humid desert in southwestern Pangea and its lower and upper contacts lead us to consider its age as Lopingian-Induan. The five sets of tracks studied were compared with several ichnotaxa and body fossils with appendicular elements preserved, allowing us to attribute these tracks to dicynodonts and other indeterminate therapsids. Even though the "Piramboia Formation" track record is sparse and sub-optimally preserved, it is an important key to better understand the occupation of arid environments by tetrapods across the Permo-Triassic boundary. PMID- 29796342 TI - Effect of elevated temperature on membrane lipid saturation in Antarctic notothenioid fish. AB - Homeoviscous adaptation (HVA) is a key cellular response by which fish protect their membranes against thermal stress. We investigated evolutionary HVA (long time scale) in Antarctic and non-Antarctic fish. Membrane lipid composition was determined for four Perciformes fish: two closely related Antarctic notothenioid species (Trematomus bernacchii and Pagothenia borchgrevinki); a diversified related notothenioid Antarctic icefish (Chionodraco hamatus); and a New Zealand species (Notolabrus celidotus). The membrane lipid compositions were consistent across the three Antarctic species and these were significantly different from that of the New Zealand species. Furthermore, acclimatory HVA (short time periods with seasonal changes) was investigated to determine whether stenothermal Antarctic fish, which evolved in the cold, stable environment of the Southern Ocean, have lost the acclimatory capacity to modulate their membrane saturation states, making them vulnerable to anthropogenic global warming. We compared liver membrane lipid composition in two closely related Antarctic fish species acclimated at 0 degrees C (control temperature), 4 degrees C for a period of 14 days in T. bernacchii and 28 days for P. borchgrevinki, and 6 degrees C for 7 days in both species. Thermal acclimation at 4 degrees C did not result in changed membrane saturation states in either Antarctic species. Despite this, membrane functions were not compromised, as indicated by declining serum osmolality, implying positive compensation by enhanced hypo-osmoregulation. Increasing the temperature to 6 degrees C did not change the membrane lipids of P. borchgrevinki. However, in T. bernacchii, thermal acclimation at 6 degrees C resulted in an increase of membrane saturated fatty acids and a decline in unsaturated fatty acids. This is the first study to show a homeoviscous response to higher temperatures in an Antarctic fish, although for only one of the two species examined. PMID- 29796343 TI - Larval exposure to the neonicotinoid imidacloprid impacts adult size in the farmland butterfly Pieris brassicae. AB - Populations of farmland butterflies have been suffering from substantial population declines in recent decades. These declines have been correlated with neonicotinoid usage both in Europe and North America but experimental evidence linking these correlations is lacking. The potential for non-target butterflies to be exposed to trace levels of neonicotinoids is high, due to the widespread contamination of agricultural soils and wild plants in field margins. Here we provide experimental evidence that field realistic, sub-lethal exposure to the neonicotinoid imidacloprid negatively impacts the development of the common farmland butterfly Pieris brassicae. Cabbage plants were watered with either 0, 1, 10, 100 or 200 parts per billion imidacloprid, to represent field margin plants growing in contaminated agricultural soils and these were fed to P. brassicae larvae. The approximate digestibility (AD) of the cabbage as well as behavioural responses by the larvae to simulated predator attacks were measured but neither were affected by neonicotinoid treatment. However, the duration of pupation and the size of the adult butterflies were both significantly reduced in the exposed butterflies compared to the controls, suggesting that adult fitness is compromised through exposure to this neonicotinoid. PMID- 29796344 TI - Effects of sandfish (Holothuria scabra) removal on shallow-water sediments in Fiji. AB - Sea cucumbers play an important role in the recycling and remineralization of organic matter (OM) in reef sands through feeding, excretion, and bioturbation processes. Growing demand from Asian markets has driven the overexploitation of these animals globally. The implications of sea cucumber fisheries for shallow coastal ecosystems and their management remain poorly understood. To address this knowledge gap, the current study manipulated densities of Holothuria scabra within enclosures on a reef flat in Fiji, between August 2015 and February 2016, to study the effects of sea cucumber removal on sedimentary function as a biocatalytic filter system. Three treatments were investigated: (i) high density (350 g m-2 wet weight; ca. 15 individuals); (ii) natural density (60 g m-2; ca. 3 individuals); and (iii) exclusion (0 g m-2). Quantity of sediment reworked through ingestion by H. scabra, grain size distribution, O2 penetration depth, and sedimentary oxygen consumption (SOC) were quantified within each treatment. Findings revealed that the natural population of H. scabra at the study site can rework ca. 10,590 kg dry sediment 1,000 m-2 year-1; more than twice the turnover rate recorded for H. atra and Stichopus chloronotus. There was a shift towards finer fraction grains in the high treatment. In the exclusion treatment, the O2 penetration depth decreased by 63% following a 6 degrees C increase in water temperature over the course of two months, while in the high treatment no such change was observed. SOC rates increased ca. two-fold in the exclusion treatment within the first month, and were consistently higher than in the high treatment. These results suggest that the removal of sea cucumbers can reduce the capacity of sediments to buffer OM pulses, impeding the function and productivity of shallow coastal ecosystems. PMID- 29796345 TI - Diagnostic accuracy of Onen's Alternative Grading System combined with Doppler evaluation of ureteral jets as an alternative in the diagnosis of obstructive hydronephrosis in children. AB - Introduction: Ureteropelvic junction obstruction (UPJO) is a common congenital anomaly leading to varying degrees of hydronephrosis (HN), ranging from no apparent effect on the renal function to atrophy. Evaluation of these children is based on Diuretic Renal Scintigraphy (DRS) and Ultrasonography (US). Recent studies have suggested that new parameters of conventional and color Doppler ultrasonography (CDUS) may be useful in discriminating which kidneys are obstructed. The present study aims to assess the diagnostic accuracy of such parameters in the diagnosis of obstruction in children with UPJO. Methods: We evaluated 44 patients (33 boys) with a mean age of 6.53 +/- 4.39 years diagnosed with unilateral high-grade hydronephrosis (SFU grades 3 and 4). All underwent DRS and index tests (conventional US and CDUS to evaluate ureteral jets frequency) within a maximum interval of two weeks. Hydronephrotic units were reclassified according to the alternative grading system (AGS) proposed by Onen et al. Obstruction in the DRS was defined as a differential renal function <40% on the affected side and/or features indicating poor drainage function like T1/2 >20 minutes after the administration of furosemide, and a plateau or ascending pattern of the excretion curve. Results: Nineteen hydronephrotic units (43.1%) were obstructed. Some degree of cortical atrophy-grades 3 (segmental) or 4 (diffuse)-was present in those obstructed units. AGS grades had 100% sensitivity, 76% of specificity and 86.4% of accuracy. The absence of ureteral jets had a sensitivity of 73.68%, a specificity of 100% with an accuracy of 88.6%. When we analyzed the two aspects together and considered obstructed the renal units classified as AGS grade 3 or 4 with no jets, sensitivity increased to 78.9%, accuracy to 92%, remaining with a maximum specificity of 100%. These features combined would allow us to avoid performing DRS in 61% of our patients, leaving more invasive tests to inconclusive cases. Conclusions: Although DRS remains the mainstay to distinguishing obstructive from non-obstructive kidneys, grade of hydronephrosis and frequency of ureteral jets, independently or in combination may be a reliable alternative in the mostly cases.This alternative approach has high accuracy, it is less invasive, easily reproducible and may play a role in the diagnosis of obstruction in pediatric population. PMID- 29796346 TI - Association of epilepsy and asthma: a population-based retrospective cohort study. AB - Background: Epidemiologic data supporting the epilepsy-asthma association are insufficient. Therefore, we examined this association in this study. Methods: By using claims data from the National Health Insurance Research Database (Taiwan), we executed a retrospective cohort analysis. Analysis 1 entailed comparing 150,827 patients diagnosed as having incident asthma during 1996-2013 with disease-free controls who were selected randomly during the same period, frequency matched in terms of age and sex. Similarly, analysis 2 entailed comparing 25,274 patients newly diagnosed as having epilepsy with sex- and age matched controls who were selected randomly. At the end of 2013, we evaluated in analysis 1 the epilepsy incidence and risk and evaluated in analysis 2 the asthma incidence and risk. We applied Kaplan-Meier analysis to derive plots of the proportion of asthma-free seizures. Results: In analysis 1, the asthma group exhibited a higher epilepsy incidence than did the control group (3.05 versus 2.26 per 1,000 person-years; adjusted hazard ratio: 1.39, 95% CI [1.33-1.45]). We also noted a greater risk of subsequent epilepsy in women and girls. In analysis 2, we determined that the asthma incidence between the control and epilepsy groups did not differ significantly; however, some age subgroups including children and individuals in their 30s had an increased risk. A negative association was found in adolescents. The Kaplan-Meier analysis revealed epilepsy to be positively associated with subsequent onset of asthma within seven years of epilepsy diagnosis. Discussion: Asthma may be associated with high epilepsy risk, and epilepsy may be associated with high asthma risk among children and individuals in their 30s. Nevertheless, people with epilepsy in other age subgroups should be aware of the possibility of developing asthma within seven years of epilepsy diagnosis. PMID- 29796348 TI - A quantitative approach to determine the taxonomic identity and ontogeny of the pycnodontiform fish Pycnodus (Neopterygii, Actinopterygii) from the Eocene of Bolca Lagerstatte, Italy. AB - Background: The pycnodontiform fish Pycnodus is one of the representatives of the highly diverse actinopterygian fish fauna from the early Eocene Bolca Lagerstatte, representing one of the youngest and thus last occurrences of this extinct neopterygian clade. This genus has historically been used as a wastebasket taxon in regards to poorly known pycnodontiform fossils. Authors have argued over the specific status of the Bolca Lagerstatte Pycnodus in terms of how many species are contained within the genus with some arguing for multiple species and others suggesting lumping all Bolca specimens together into one species. Methods: Here, we use a quantitative approach performing biometric and geometric morphometric analyses on 52 specimens of Pycnodus in order to determine if the morphological variability within the sample might be related to inter- or intraspecific variation. Results: The analyses revealed that the variations of body shape, morphometric and meristic characters cannot be used to distinguish different morphotypes. On the contrary, our results show a remarkable link between shape and size, related to ontogeny. Discussion: Differences in body shape of small (juvenile) and large (adult) individuals is probably related to different microhabitats occupation on the Bolca reef with juveniles sheltering within crevices on the reef and adults being more powerful swimmers that swim above the coral. Taxonomically, we suggest that the Bolca Pycnodus should be referred to strictly as Pycnodus apodus as this was the name given to the holotype. Additionally, an overview of species assigned to Pycnodus is given. PMID- 29796347 TI - Helicobacter pylori genetic diversification in the Mongolian gerbil model. AB - Helicobacter pylori requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed H. pylori genetic adaptation in the Mongolian gerbil model. This model is of particular interest because H. pylori-infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration. We analyzed the whole genome sequences of H. pylori strains cultured from experimentally infected gerbils, in comparison to the genome sequence of the input strain. The mean annualized single nucleotide polymorphism (SNP) rate per site was 1.5e-5, which is similar to the rates detected previously in H. pylori infected humans. Many of the mutations occurred within or upstream of genes associated with iron-related functions (fur, tonB1, fecA2, fecA3, and frpB3) or encoding outer membrane proteins (alpA, oipA, fecA2, fecA3, frpB3 and cagY). Most of the SNPs within coding regions (86%) were non-synonymous mutations. Several deletion or insertion mutations led to disruption of open reading frames, suggesting that the corresponding gene products are not required or are deleterious during chronic H. pylori colonization of the gerbil stomach. Five variants (three SNPs and two deletions) were detected in isolates from multiple animals, which suggests that these mutations conferred a selective advantage. One of the mutations (FurR88H) detected in isolates from multiple animals was previously shown to confer increased resistance to oxidative stress, and we now show that this SNP also confers a survival advantage when H. pylori is co cultured with neutrophils. Collectively, these analyses allow the identification of mutations that are positively selected during H. pylori colonization of the gerbil model. PMID- 29796350 TI - I understand you feel that way, but I feel this way: the benefits of I-language and communicating perspective during conflict. AB - Using hypothetical scenarios, we provided participants with potential opening statements to a conflict discussion that varied on I/you language and communicated perspective. Participants rated the likelihood that the recipient of the statement would react in a defensive manner. Using I-language and communicating perspective were both found to reduce perceptions of hostility. Statements that communicated both self- and other-perspective using I-language (e.g. 'I understand why you might feel that way, but I feel this way, so I think the situation is unfair') were rated as the best strategy to open a conflict discussion. Simple acts of initial language use can reduce the chances that conflict discussion will descend into a downward spiral of hostility. PMID- 29796351 TI - Multimodal Imaging in Extratemporal Epilepsy Surgery. AB - Neuroimaging is crucial for the evaluation of patients considered for resective epilepsy surgery. Multimodal image fusion is a new tool to integrate all available localizing information on the individual epileptogenic network in a three-dimensional (3D) manner to plan invasive EEG recordings and delineate the epileptogenic zone from the eloquent cortex for the neurosurgical planning of a tailored resection. Here, we illustrate the multimodal fusion of images from different modalities in a patient with medically intractable non-lesional frontal lobe epilepsy who underwent partial frontal lobe resection, rendering him seizure free. PMID- 29796349 TI - Fitness consequences of fish circadian behavioural variation in exploited marine environments. AB - The selective properties of fishing that influence behavioural traits have recently gained interest. Recent acoustic tracking experiments have revealed between-individual differences in the circadian behavioural traits of marine free living fish; these differences are consistent across time and ecological contexts and generate different chronotypes. Here, we hypothesised that the directional selection resulting from fishing influences the wild circadian behavioural variation and affects differently to individuals in the same population differing in certain traits such as awakening time or rest onset time. We developed a spatially explicit social-ecological individual-based model (IBM) to test this hypothesis. The parametrisation of our IBM was fully based on empirical data; which represent a fishery formed by patchily distributed diurnal resident fish that are exploited by a fleet of mobile boats (mostly bottom fisheries). We ran our IBM with and without the observed circadian behavioural variation and estimated selection gradients as a quantitative measure of trait change. Our simulations revealed significant and strong selection gradients against early riser chronotypes when compared with other behavioural and life-history traits. Significant selection gradients were consistent across a wide range of fishing effort scenarios. Our theoretical findings enhance our understanding of the selective properties of fishing by bridging the gaps among three traditionally separated fields: fisheries science, behavioural ecology and chronobiology. We derive some general predictions from our theoretical findings and outline a list of empirical research needs that are required to further understand the causes and consequences of circadian behavioural variation in marine fish. PMID- 29796352 TI - Why We Need a Single Definition of Disruptive Behavior. AB - Disruptive behavior is known to produce a wide range of negative effects in healthcare, such as impacting patient safety, lowering employee morale, and decreasing employee retention. Healthcare organizations have worked towards eliminating disruptive behavior; however, despite countless interventions, the issue continues to be a problem today. Why then does the issue of disruptive behavior persist? We argue that one reason is the multiple ways disruptive behavior can be described, henceforth defined as the "plurality of terms", which can make it difficult to collect relevant data by doing a simple literature search. Hence, we believe having a single definition for "disruptive behavior" will improve the meta-analysis on disruptive behavior research. PMID- 29796353 TI - The Current Trend of the Translational Research Paradigm. AB - The translational research paradigm is a process of discovering basic science concepts and applying the knowledge in clinical practice, aiming to improve patient care. The stages involved in the paradigm form a complex network of shared knowledge amongst research collaborators, including patients. This nature of the paradigm allows those involved to work together effectively. However, the translational research paradigm is often overlooked by many scientists, educators, and research institutions. Hence, a large amount of comprehensive and hugely invested research projects fail to make a scientific impact. We aim to outline and describe this paradigm in order to aid in the successful translation of effective research. PMID- 29796354 TI - A Gender-based Comparison in Health Behaviors and State of Happiness among University Students. AB - Objective The presence of good healthy behaviors among university students is imperative for their future life. This study aimed to compare positive health behaviors and state of happiness between the two genders of Bahria University (BU), Karachi, Pakistan. Subjects and methods This cross-sectional study was conducted at BU, Karachi, Pakistan. A total 813 students participated in this study. The health questionnaire, adapted from Health and Behavior Survey and the Subjective Happiness Scale, was used to assess self-reported happiness. The data were analyzed using IBM SPSS version 22. Results Overall self-reported health behaviors were found to be more prevalent in females as compared to males, but males reported a better self-reported general health (p = 0.012). Testicular and breast self-examination was not common in both genders. Smoking was found to be more common in males (p < 0.01). Males exhibited habit of regular breakfast (p = 0.013) whereas females showed a tendency to avoid food rich in cholesterol and fat (p < 0.01) and the practice of consuming food rich in fiber was found to be more prevalent among females (p < 0.01) and they showed urge to lose weight (p < 0.01). Sleep disturbance was found in both genders, more so in females (p = 0.012). Consciousness about dental hygiene was common in females (p < 0.01). As compared to the females, more males strongly believe that they are very happy in life (p < 0.01), and they make the most out of everything in life (p < 0.01). Conclusion There was a diverse response to positive health behaviors and state of happiness in both genders. PMID- 29796355 TI - Fenestration of the Proximal Left Ovarian Vein. AB - A fenestration in the left ovarian vein was found in a fresh-frozen female cadaver. The opening did not have any vessels or additional anatomical structures passing through it. The ovarian vein is also referred to as the female gonadal vein. This type of anatomical variation is clinically relevant in procedures that deal with the manipulation of the gonadal veins, specifically conditions such as ovarian vein thrombosis, ovarian vein stenosis, and pelvic congestion syndrome. PMID- 29796357 TI - Academic Life in Emergency Medicine (ALiEM) Blog and Podcast Watch: Infectious Disease Emergencies. AB - To address the needs for curation of online educational content as well as the development of a nationally available curriculum that meets individualized interactive instruction, the Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) Series and AIR-Pro Series were created in 2014 and 2015, respectively. Using an expert-based, crowd-sourced approach, these two programs identify trustworthy, high-quality, educational blog, and podcast content. Here, we summarize the accredited posts that met our a priori determined quality criteria and evaluated by eight attending physicians. PMID- 29796356 TI - MicroRNAs as Potential Serum Biomarkers for Early Detection of Ectopic Pregnancy. AB - Diagnosis of ectopic pregnancy relies on both ultrasound findings and human chorionic gonadotropin (hCG) measurements but due to the need for serial tests, tubal rupture and death represent major maternal and fetal risks. Early detection of ectopic pregnancy is essential and thus a noninvasive diagnostic tool seems crucial for the prevention of adverse effects since studies suggest there is a specific relationship between ectopic pregnancy and increasing microRNA factors. Human fluids in women with ectopic pregnancy reveal a particular change in comparison to healthy women. In addition to certain placental microRNAs circulating through plasma that present a specific concentration and serum profile, microRNAs seem to be possible biomarkers for the detection of pregnancy complications linked to placental pathologies. The aim of this study is to review current literature considering the expression levels of several circulating microRNAs that have shown to be novel potential biomarkers for the diagnosis of tubal ectopic pregnancy. PMID- 29796359 TI - Acute Appendicitis in Young Children: A Persistent Diagnostic Challenge for Clinicians. AB - Acute appendicitis is a grave and life-threatening condition in children, accounting for one to two cases per 10,000 in children less than four years' old. Prompt diagnosis and management are imperative to prevent serious complications, such as abscess formation, perforation, bowel obstruction, peritonitis, and sepsis. In young children, however, the diagnosis of this condition is challenging. The delayed utilization of imaging may further delay the diagnosis due to concerns of exposure to ionizing radiation. Even with a prompt diagnosis, controversy persists regarding medical versus operative management in these young patients. We report a case of a 21-month-old female who presented with fever, non bilious, non-bloody emesis, and decreased tolerance for liquids and solids. The initial physical exam and imaging were suggestive of non-obstructive bowel distention. The patient was admitted to the pediatric floor. Overnight, the patient's condition deteriorated severely and became septic. Repeat imaging revealed a 9-cm appendicular mass and a ruptured appendix. Antibiotic coverage was then broadened and the patient was transferred to the critical care unit for more intensive management. The patient's septic condition improved over the upcoming few days and the parents elected to perform an elective appendectomy following resolution of the condition. Atypical presentations are common in this population. The difficulty in obtaining a reliable history and physical examination findings makes the diagnosis even more challenging. Moreover, concerns with radiation exposure may delay the diagnosis and increase the risk of perforation and peritonitis. Thus, clinicians should have a high index of suspicion for acute appendicitis, particularly in young children, as this condition is commonly missed on initial presentation. PMID- 29796358 TI - Daily Tracking of Glioblastoma Resection Cavity, Cerebral Edema, and Tumor Volume with MRI-Guided Radiation Therapy. AB - Radiation therapy (RT) plays a critical role in the treatment of glioblastoma. Studies of brain imaging during RT for glioblastoma have demonstrated changes in the brain during RT. However, frequent or daily utilization of standalone magnetic resonance imaging (MRI) scans during RT have limited feasibility. The recent release of the tri-cobalt-60 MRI-guided RT (MR-IGRT) device (ViewRay MRIdian, Cleveland, OH) allows for daily brain MRI for the RT setup. Daily MRI of three postoperative patients undergoing RT and temozolomide for glioblastoma over a six-week course allowed for the identification of changes to the cavity, edema, and visible tumor on a daily basis. The volumes and dimensions of the resection cavities, edema, and T2-hyperintense tumor were measured. A general trend of daily decreases in cavity measurements was observed in all patients. For the one patient with edema, a trend of daily increases followed by a trend of daily decreases were observed. These results suggest that daily MRI could be used for onboard resimulation and adaptive RT for future fluctuations in the sizes of brain tumors, cavities, or cystic components. This could improve tumor targeting and reduce RT of healthy brain tissue. PMID- 29796360 TI - Increased Cancer Risk in Younger Patients with Thyroid Nodules Diagnosed as Atypia of Undetermined Significance. AB - BACKGROUND: The objective of this study was to determine if patient age and/or gender significantly alter the risk of thyroid malignancy in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) diagnostic categories. METHODS: A retrospective review of 291 sequential patients that underwent thyroid nodule fine needle aspiration biopsy (FNAB) and subsequent surgery at a single center was carried out. Cases were grouped according to age (55 years and older versus younger than 55 years) and gender. The cancer risk was calculated for each BSRTC diagnostic group. A p-value <0.05 was not considered statistically significant. RESULTS: The study population was composed of 291 patients (227 females and 64 males). Histopathology diagnosed cancer in 113 cases (39%). The cancer risk was significantly increased in cases with a BSRTC diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in patients younger than 55 years of age (36.8% vs 7.4%, p=0.0082). CONCLUSIONS: Though thyroid cancer was significantly more common in males (p=0.021), gender did not significantly influence specific BRSTC diagnostic category cancer risk estimation. A BSRTC AUS/FLUS diagnosis is associated with an increased cancer risk in younger patients. PMID- 29796361 TI - Strongyloides Hyperinfection and Miliary Tuberculosis Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Malnourished Patient. AB - Strongyloides stercoralis (S. stercoralis) is an intestinal nematode endemic to tropical regions. An accelerated infection, known as a hyperinfection, occurs in immunocompromised patients, most commonly those treated chronically with glucocorticoids or those who have human T cell leukemia virus-1 (HTLV-1) infection. We describe a 67-year-old Hispanic female who presented with complaints of decreased oral intake and fatigue since three months. Hyponatremia on initial presentation was attributed to syndrome of inappropriate antidiuretic hormone (SIADH) secretion and managed with fluid restriction. Computed tomography (CT) of the chest revealed multiple pulmonary nodules suggestive of miliary tuberculosis, however, sputum acid-fast bacilli (AFB) smears were negative. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed and specimens sent for AFB testing. A concurrent endoscopy with biopsy was done to evaluate dysphagia. Both respiratory and gastrointestinal (GI) specimens were positive for Strongyloides stercoralis. Treatment with ivermectin and prophylactic antibiotics was started. The patient developed septic shock and had multiple episodes of gastrointestinal bleeding. Despite aggressive management, she expired. Subsequently, cultures for Mycobacterium tuberculosis (MTB) were positive and the autopsy demonstrated evidence of MTB infection in the lungs, liver, and lymph nodes. This case illustrates the importance of considering co infection with Strongyloides stercoralis in patients with MTB, both associated with depressed cellular immunity. PMID- 29796362 TI - Small Bowel Obstruction due to Non-steroidal Anti-inflammatory Drug-induced Diaphragm Disease: A Case Report. AB - Small bowel obstruction (SBO) is a common illness encountered by general surgeons. However, obstruction caused by diaphragm disease induced by non steroidal anti-inflammatory drug (NSAID) is exceedingly rare. The diagnosis is challenging as the signs and symptoms are neither sensitive nor specific. We report the case of a 59-year-old male who presented with SBO secondary to this uncommon condition. We hope to raise awareness of this unusual entity. PMID- 29796363 TI - Chilaiditi's Sign Associated with Acute Colonic Pseudo-obstruction: A Radiological Diagnosis. AB - Chilaiditi's sign is a rare radiological anomaly of hepato-diaphragmatic interposition of the bowel. We report a case of Chilaiditi's sign associated with acute colonic pseudo-obstruction. A 90-year-old male was admitted for hypertensive emergency. His physical examination showed a distended abdomen, decreased bowel sounds, and right upper quadrant tenderness. A chest radiograph demonstrated marked elevation of the right diaphragm and interposition of the hepatic flexure of the colon between the diaphragm and the liver, along with marked gaseous distension up to 9 cm in the ascending colon without any small bowel distension. The patient was managed conservatively with bowel rest, stool softeners, enemas, and intravenous (IV) hydration. The patient improved clinically with resolution of colonic distension. Chilaiditi's sign and Chilaiditi syndrome are rare entities and therefore are often misdiagnosed and mismanaged. Awareness of the radiological sign, the syndrome itself, and the association with acute colonic pseudo-obstruction is important for all care providers so that they can opt for more conservative management strategies instead of unnecessary interventions including surgeries. PMID- 29796364 TI - Pregnancy-related Hemophagocytic Lymphohistiocytosis Associated with Herpes Simplex Virus-2 Infection: A Diagnostic Dilemma. AB - Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disorder characterized by the uncontrolled proliferation of lymphocytes and histiocytes with hemophagocytic activity in the bone marrow. To our knowledge, there have been a few reported cases of pregnancy-related HLH. This case highlights the importance of considering HLH in a pregnant woman along with other diagnoses, such as HELLP (which stands for hemolysis, elevated liver enzyme levels, and low platelet levels) syndrome and hemolytic anemias. It points to the challenges of diagnosing and managing pregnancy-related HLH due to a similarity in presentation with other conditions. PMID- 29796366 TI - Evaluation of the Multi-Angle Implementation of Atmospheric Correction (MAIAC) Aerosol Algorithm through Intercomparison with VIIRS Aerosol Products and AERONET. AB - The Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm is under evaluation for use in conjunction with the Geostationary Coastal and Air Pollution Events (GEO-CAPE) mission. Column aerosol optical thickness (AOT) data from MAIAC are compared against corresponding data from the Visible Infrared Imaging Radiometer Suite (VIIRS) instrument over North America during 2013. Product coverage and retrieval strategy, along with regional variations in AOT through comparison of both matched and un-matched seasonally gridded data are reviewed. MAIAC shows extended coverage over parts of the continent when compared to VIIRS, owing to its pixel selection process and ability to retrieve aerosol information over brighter surfaces. To estimate data accuracy, both products are compared with AERONET Level 2 measurements to determine the amount of error present and discover if there is any dependency on viewing geometry and/or surface characteristics. Results suggest that MAIAC performs well over this region with a relatively small bias of -0.01; however there is a tendency for greater negative biases over bright surfaces and at larger scattering angles. Additional analysis over an expanded area and longer time period are likely needed to determine a comprehensive assessment of the products capability over the Western Hemisphere. PMID- 29796365 TI - Maxillary Teeth Abscesses Result in Atypical Liver Abscesses. AB - Hepatic liver abscesses are often misdiagnosed on initial presentation because pyogenic liver lesions are a rare occurrence in the United States. This leads to a delay in proper treatment and results in increasing morbidity and mortality. Our case report demonstrates the atypical presentation of a hepatic liver abscess in the elderly. The source of infection was found to be periapical abscesses of the teeth, which subsequently seeded the portal blood stream of our patient. Our findings validate the potential hazard of Viridans streptococci and illustrate how untreated dental infections can serve as a reservoir for a systemic infection. PMID- 29796367 TI - Recognizing Our Experts: Global Spine Journal Partners with Publons to Establish Reviewers' Platform. PMID- 29796368 TI - Adverse Outcomes and Prediction of Cardiopulmonary Complications in Elective Spine Surgery. AB - Study Design: Retrospective cohort study. Objectives: The purpose of this study was to report incidence of cardiopulmonary complications in elective spine surgery, demographic and surgical predictors, and outcomes. Understanding the risks and predictors of these sentinel events is important for risk evaluation, allocation of hospital resources, and counseling patients. Methods: A retrospective review of the National Surgical Quality Improvement Program (NSQIP) was performed on 60 964 patients undergoing elective spine surgery (any region; laminectomy, arthrodesis, discectomy, or laminoplasty) between 2011 and 2013. Incidence of myocardial infarction, cardiac arrest, unplanned reintubation, on ventilator >48 hours, perioperative pneumonia, and pulmonary embolism was measured. Demographic and surgical predictors of cardiopulmonary complications and associated outcomes (length of stay, discharge disposition, and mortality) were measured using binary logistic regression controlling for confounders. Results: Incidence rates per 1000 elective spine patients were 2.1 myocardial infarctions, 1.3 cardiac arrests, 4.3 unplanned intubations, 3.5 on ventilator >48 hours, 6.1 perioperative pneumonia, and 3.7 pulmonary embolisms. In analysis of procedure, diagnosis, and approach risk factors, thoracic cavity (odds ratio = 2.47; confidence interval = 1.95-3.12), scoliosis diagnosis, and combined approach (odds ratio = 1.51; confidence interval = 1.15-1.96) independently added the most risk for cardiopulmonary complication. Cardiac arrest had the highest mortality rate (34.57%). Being on ventilator greater than 48 hours resulted in the greatest increase to length of stay (17.58 days). Conclusions: Expected risk factors seen in the Revised Cardiac Risk Index were applicable in the context of spine surgery. Surgical planning should take into account patients who are at higher risk for cardiopulmonary complications and the implications they have on patient outcome. PMID- 29796369 TI - Clinically Significant Thromboembolic Disease in Adult Spinal Deformity Surgery: Incidence and Risk Factors in 737 Patients. AB - Study Design: Retrospective cohort study. Objectives: Describe the rate and risk factors for venous thromboembolic events (VTEs; defined as deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) in adult spinal deformity (ASD) surgery. Methods: ASD patients with VTE were identified in a prospective, multicenter database. Complications, revision, and mortality rate were examined. Patient demographics, operative details, and radiographic and clinical outcomes were compared with a non-VTE group. Multivariate binary regression model was used to identify predictors of VTE. Results: A total of 737 patients were identified, 32 (4.3%) had VTE (DVT = 14; PE = 18). At baseline, VTE patients were less likely to be employed in jobs requiring physical labor (59.4% vs 79.7%, P < .01) and more likely to have osteoporosis (29% vs 15.1%, P = .037) and liver disease (6.5% vs 1.4%, P = .027). Patients with VTE had a larger preoperative sagittal vertical axis (SVA; 93 mm vs 55 mm, P < .01) and underwent larger SVA corrections. VTE was associated with a combined anterior/posterior approach (45% vs 25%, P = .028). VTE patients had a longer hospital stay (10 vs 7 days, P < .05) and higher mortality rate (6.3% vs 0.7%, P < .01). Multivariate analysis demonstrated osteoporosis, lack of physical labor, and increased SVA correction were independent predictors of VTE (r2 = .11, area under the curve = 0.74, P < .05). Conclusions: The incidence of VTE in ASD is 4.3% with a DVT rate of 1.9% and PE rate of 2.4%. Osteoporosis, lack of physical labor, and increased SVA correction were independent predictors of VTE. Patients with VTE had a higher mortality rate compared with non-VTE patients. PMID- 29796370 TI - Immediate Postoperative Pain Scores Predict Neck Pain Profile up to 1 Year Following Anterior Cervical Discectomy and Fusion. AB - Study Design: Retrospective cohort review. Objective: To assess whether immediate postoperative neck pain scores accurately predict 12-month visual analog scale neck pain (VAS-NP) outcomes following Anterior Cervical Discectomy and Fusion surgery (ACDF). Methods: This was a retrospective study of 82 patients undergoing elective ACDF surgery at a major academic medical center. Patient reported outcomes measures VAS-NP scores were recorded on the first postoperative day, then at 6-weeks, 3, 6, and 12-months after surgery. Multivariate correlation and logistic regression methods were utilized to determine whether immediate postoperative VAS-NP score accurately predicted 1-year patient reported VAS-NP Scores. Results: Overall, 46.3% male, 25.6% were smokers, and the mean age and body mass index (BMI) were 53.7 years and 28.28 kg/m2, respectively. There were significant correlations between immediate postoperative pain scores and neck pain scores at 6 weeks VAS-NP (P = .0015), 6 months VAS-NP (P = .0333), and 12 months VAS-NP (P = .0247) after surgery. Furthermore, immediate postoperative pain score is an independent predictor of 6 weeks, 6 months, and 1 year VAS-NP scores. Conclusion: Our study suggests that immediate postoperative patient reported neck pain scores accurately predicts and correlates with 12-month VAS-NP scores after an ACDF procedure. Patients with high neck pain scores after surgery are more likely to report persistent neck pain 12 months after index surgery. PMID- 29796371 TI - Influence of Gender on Health-Related Quality of Life and Disability at 1 Year After Surgery for Thoracolumbar Burst Fractures. AB - Study Design: Case series. Objective: Thoracolumbar burst fractures (TLBF) are the most frequent type of spinal fractures. Approximately half of the patients are neurologically intact and their treatment is still debatable. Gender could influence outcome after surgical procedures, but this is still unclear in patients sustaining a spinal fracture. The aim of this study was to investigate how gender influences health-related quality of life (HRQOL) and disability in patients operated on for TLBF. Methods: We identified 44 neurologically intact patients from a consecutive series of patients treated surgically for a single level traumatic burst fracture (AOSpine Subaxial Classification System A3) in the thoracolumbar transition area (Th12-L2). At 1 year after surgery, they were evaluated using the SF-36v2 questionnaire to assess HRQOL and Oswestry Disability Index (ODI) questionnaire to evaluate disability. Results: Male patients scored higher in each item of the SF-36v2, with significant differences (P < .05) for Physical Function (PF), Bodily Pain (BP), and Social Function (SF). Male patients also had lower disability scores. Overall ODI score had a strong correlation with Physical Function, Role-Physical, Bodily Pain, Vitality, Mental Health, and overall Physical Component Summary (PCS) of the SF-36 in women, but only with Physical Function, Role-Physical, Role-Emotional, and PCS in men. Conclusions: In this study, male patients reported better outcomes at 1 year after surgery for TLBF than women. Disability strongly correlated with the overall HRQOL, physical and mental health in women, but not in men. We found gender-related differences favoring men after surgical interventions for spinal fractures. PMID- 29796372 TI - National Trends in Demographics and Outcomes Following Cervical Fusion for Cervical Spondylotic Myelopathy. AB - Study Design: Retrospective trends analysis. Objectives: Cervical fusion is a common adjunctive surgical modality used in the treatment of cervical spondylotic myelopathy (CSM). The purpose of this study was to quantify national trends in patient demographics, hospital characteristics, and outcomes in the surgical management of CSM. Methods: This was a retrospective study that used the National Inpatient Sample. The sample included all patients over 18 years of age with a diagnosis of CSM who underwent cervical fusion from 2003 to 2013. The outcome measures were in-hospital mortality, length of stay, and hospital charges. Chi square tests were performed to compare categorical variables. Independent t tests were performed to compare continuous variables. Results: We identified 62 970 patients with CSM who underwent cervical fusion from 2003 to 2013. The number of fusions performed per year in the treatment of CSM increased from 3879 to 8181. The average age of all fusion patients increased from 58.2 to 60.6 years (P < .001). Length of stay did not change significantly from a mean of 3.7 days. In hospital mortality decreased from 0.6% to 0.3% (P < .01). Hospital charges increased from $49 445 to $92 040 (P < .001). Conclusions: This study showed a dramatic increase in cervical fusions to treat CSM from 2003 to 2013 concomitant with increasing age of the patient population. Despite increases in average age and number of comorbidities, length of stay remained constant and a decrease in mortality was seen across the study period. However, hospital charges increased dramatically. PMID- 29796373 TI - Patterns of Cervical Disc Degeneration: Analysis of Magnetic Resonance Imaging of Over 1000 Symptomatic Subjects. AB - Study Design: Cross-sectional study. Objectives: The aim of this study was to evaluate cervical disc degeneration on magnetic resonance imaging (MRI) in a large population of symptomatic patients and to provide baseline data on the pattern of degeneration in order to understand how the cervical spine ages. Methods: We performed a cross-sectional study of 1059 patients who underwent upright cervical MRI for neck pain with and without neurological symptoms. A total of 6354 cervical discs from C2/3 to C7/T1 were evaluated. Cervical disc degeneration was evaluated on T2-weighted MRI and graded into 4 categories (Grades 0-III). Positive degeneration was defined as greater than Grade II. The correlation between age and total grade of degeneration of each patient was evaluated, as well as the prevalence and pattern of degeneration. Results: The average number of degenerated disc levels and the total grade of cervical disc degeneration significantly increase with age. In the patient group with 1-level degeneration, C5/6 was the most common degenerated level followed by C4/5 and C6/7. In the group with 2-level degeneration, C5/6 & C6/7 was most common followed by C4/5 & C5/6 and C3/4 & C4/5. Skip level degeneration was significantly rarer than contiguous level degeneration, and C7/T1 and C2/3 were the most unlikely to degenerate in multilevel degeneration. Conclusion: Disc degeneration is most common in the middle cervical spine (C5/6) and progresses to contiguous levels, except for C7/T1 and C2/3. This pattern may play a role in adjacent-level disc degeneration associated with spinal fusion. PMID- 29796375 TI - Predictors for Non-Home Patient Discharge Following Elective Adult Spinal Deformity Surgery. AB - Study Design: Retrospective cohort study. Objectives: Adult spinal deformity (ASD) surgery encompasses a wide variety of spinal disorders and is associated with a morbidity rate between 20% and 80%. The utilization of spinal surgery has increased and this trend is expected to continue. To effectively deal with an increasing patient volume, identifying variables associated with patient discharge destination can expedite placement and reduce length of stay. Methods: The 2013-2014 American College of Surgeons National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Classification of Diseases, Ninth Revision diagnosis codes relevant to ASD. Patients were divided based on discharge destination. Bivariate and multivariate logistic regression analyses were employed to identify predictors for patient discharge destination and hospital length of stay. Results: A total of 4552 patients met inclusion criteria, of which 1102 (24.2%) had non-home discharge. Multivariate regression revealed total relative value unit (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 1.00-1.01); female sex (OR = 1.54, 95% CI = 1.32-1.81); American Indian, Alaska Native, Asian, Native Hawaiian, or Pacific Islander versus black race (OR = 0.52, 95% CI = 0.35-0.78, P = .002); age >=65 years (OR = 3.72, 95% CI = 3.19-4.35); obesity (OR = 1.18, 95% CI = 1.01 1.38, P = .034); partially/totally functionally dependent (OR = 2.11, 95% CI = 1.49-2.99); osteotomy (OR = 1.42, 95% CI = 1.12-1.80, P = .004) pelvis fixation (OR = 2.38, 95% CI = 1.82-3.11); operation time >=4 hours (OR = 1.74, 95% CI = 1.47-2.05); recent weight loss (OR = 7.66, 95% CI = 1.52-38.65; P = .014); and American Society of Anesthesiologists class >=3 (OR = 1.80, 95% CI = 1.53-2.11) as predictors of non-home discharge. P values were <.001 unless otherwise noted. Additionally, multivariate regression found non-home discharge to be a significant variable in prolonged length of stay. Conclusions: The authors suggest these results can be used to inform patients preoperatively of expected discharge destination, anticipate patient discharge needs postoperatively, and reduce health care costs and morbidity associated with prolonged LOS. PMID- 29796374 TI - Predictive Factors for Percutaneous Endoscopic Gastrostomy Tube Placement After Anterior Cervical Fusion. AB - Study Design: Retrospective case-control study. Objectives: To identify incidence and risk factors for percutaneous endoscopic gastrostomy (PEG) tube placement after anterior cervical fusion (ACF). Methods: Adult patients undergoing elective ACF with/without corpectomy for spondylosis from 2002 to 2011 were identified using the Nationwide Inpatient Sample database. The primary outcome measure was PEG tube placement; secondary outcomes included in-hospital mortality, total hospital charges, and discharge disposition. Multiple regression analyses were conducted to identify independent predictors of PEG tube placement. Results: Of 164 097 patients, 217 (0.13%) required a PEG tube. Patients needing PEG tube placement were older (69 vs 52 years; P < .001) and more likely to be male (65% vs 46.6%; P < .001) when compared with control patients. After regression analysis, age over 65 year (odds ratio [OR] = 4.16; P < .001) was the strongest independent predictor for PEG tube placement; other associated factors included male gender (OR = 2.14; P < .001), congestive heart failure (OR = 4.11; P < .001), anemia (OR = 3.52; P < .001), alcohol abuse (OR = 2.80; P = .009), renal failure (OR = 2.25; P = .003), chronic lung disease (OR = 1.78; P < .001), corpectomy (OR = 2.16; P < .001), and fusion of >=3 segments (OR = 1.74; P < .001). Mortality rate for patients requiring PEG tube placement was 5.1% versus 0.05% for controls (P < .001); average hospital charges were $134 379 versus $39 519 (P < .001), and nonroutine discharges were seen in 89.3% versus only 6.4% for controls (P < .001). Conclusions: The incidence of PEG tube placement after ACF was 0.13% in this study. Identified risk factors included age >65, corpectomy, fusion of >=3 segments, and various comorbidities. Additionally, there may be increased risk of in-hospital mortality, hospital charges, and nonroutine discharges among these patients. PMID- 29796376 TI - Publication Rate of Podium Presentations From the North American Spine Society Annual Meetings. AB - Study Design: Observational study. Objectives: To determine the publication rate of podium presentations from the North American Spine Society (NASS) annual meetings from the years 2009 to 2011. Methods: In April 2015, a PubMed search was conducted using titles from the paper presentations as well as the authors. Of the search results that were found, the specific scientific journal in which the article was published was recorded. We analyzed further the top 4 destination journals and trends in publications in these journals over the study period. No study funding was obtained for this research, and there are no potential conflicts of interest or associated biases. Results: Over the study period, 671 paper presentations were available and 342 were published (51% publication rate). The highest publication rate was from the 2011 annual meeting, with 55.3%, and the lowest year was 2010, with a rate of 46.43%. Spine (32.75%), The Spine Journal (19.01%), Journal of Neurosurgery Spine (7.31%), and European Spine Journal (6.73%) were the top 4 destination journals. Over the study period, we found a significant decrease in publication rate in Spine (P = .001) and a significant increase in publication rate in The Spine Journal (P = .003). There were no significant difference in publication rate over the study period in Journal of Neurosurgery Spine (P = .15) or European Spine Journal (P = .23). Conclusions: This is the first study to our knowledge evaluating the publication rate of podium presentations from recent North American Spine Society annual meetings. We found an overall publication rate of 51%. PMID- 29796377 TI - The Prognostic Accuracy of Suggested Predictors of Failure of Medical Management in Patients With Nontuberculous Spinal Epidural Abscess. AB - Study Design: Retrospective cohort study. Objectives: To test the external validity of the 2 published prediction criteria for failure of medical management in patients with spinal epidural abscess (SEA). Methods: Patients with SEA over a 10-year period at a tertiary care center were identified using ICD-10 (International Classification of Diseases, 10th Revision) diagnostic codes; electronic and paper charts were reviewed. The incidence of SEA and the proportion of patients with SEA that were treated medically were calculated. The rate of failure of medical management was determined. The published prediction models were applied to our data to determine how predictive they were of failure in our cohort. Results: A total of 550 patients were identified using ICD-10 codes, 160 of whom had a magnetic resonance imaging-confirmed diagnosis of SEA. The incidence of SEA was 16 patients per year. Seventy-five patients were found to be intentionally managed medically and were included in the analysis. Thirteen of these 75 patients failed medical management (17%). Based on the published prediction criteria, 26% (Kim et al) and 45% (Patel et al) of our patients were expected to fail. Conclusions: Published prediction models for failure of medical management of SEA were not valid in our cohort. However, once calibrated to our cohort, Patel's model consisting of positive blood culture, presence of diabetes, white blood cells >12.5, and C-reactive protein >115 was the better model for our data. PMID- 29796378 TI - Corticosteroid Administration to Prevent Complications of Anterior Cervical Spine Fusion: A Systematic Review. AB - Study Design: Systematic review. Objectives: Anterior cervical approach is associated with complications such as dysphagia and airway compromise. In this study, we aimed to systematically review the literature on the efficacy and safety of corticosteroid administration as a preventive measure of such complications in anterior cervical spine surgery with fusion. Methods: Following a systematic literature search of MEDLINE, Embase, and Cochrane databases in July 2016, all comparative human studies that evaluated the effect of steroids for prevention of complications in anterior cervical spine surgery with fusion were included, irrespective of number of levels and language. Risk of bias was assessed using MINORS (Methodological Index for Non-Randomized Studies) checklist and Cochrane Back and Neck group recommendations, for nonrandomized and randomized studies, respectively. Results: Our search yielded 556 articles, of which 9 studies (7 randomized controlled trials and 2 non-randomized controlled trials) were included in the final review. Dysphagia was the most commonly evaluated complication, and in most studies, its severity or incidence was significantly lower in the steroid group. Although prevertebral soft tissue swelling was less commonly assessed, the results were generally in favor of steroid use. The evidence for airway compromise and length of hospitalization was inconclusive. Steroid-related complications were rare, and in both studies that evaluated the fusion rate, it was comparable between steroid and control groups in long-term follow-up. Conclusions: Current literature supports the use of steroids for prevention of complications in anterior cervical spine surgery with fusion. However, evidence is limited by substantial risk of bias and small number of studies reporting key outcomes. PMID- 29796380 TI - The Anatomy of Data. PMID- 29796379 TI - Worldwide Steroid Prescription for Acute Spinal Cord Injury. AB - Study Design: Cross-sectional study. Objectives: To continue the line of a previous publication using steroid for acute spinal cord injury (SCI) by spine surgeons from Latin America (LA) and assess the current status of methylprednisolone (MP) prescription in Europe (EU), Asia Pacific (AP), North America (NA), and Middle East (ME) to determine targets for educational activities suitable for each region. Methods: The English version of a previously published questionnaire was used to evaluate opinions about MP administration in acute SCI in LA, EU, AP, NA, and ME. This Internet-based survey was conducted by members of AOSpine. The questionnaire asked about demographic features, background with management of spine trauma patients, routine administration of MP in acute SCI, and reasons for MP administration. Results: A total of 2659 responses were obtained for the electronic questionnaire from LA, EU, AP, NA, and ME. The number of spine surgeons that treat SCI was 2206 (83%). The steroid was used by 1198 (52.9%) surgeons. The uses of MP were based predominantly on the National Acute Spinal Cord Injury Study III study (n = 595, 50%). The answers were most frequently given by spine surgeons from AP, ME, and LA. These regions presented a statistically significant difference from North America (P < .001). The number of SCI patients treated per year inversely influenced the use of MP. The higher the number of patients treated, the lower the administration rates of MP observed. Conclusions: The study identified potential targets for educational campaigns, aiming to reduce inappropriate practices of MP administration. PMID- 29796381 TI - Magnetic Compression Anastomosis in Long-Gap Esophageal Atresia Gross Type A: A Case Report. AB - Esophageal atresia (EA) Gross type A (long-gap without tracheoesophageal fistula) is a rare and a surgical challenging form of EA that constitutes ~6% of the children born with EA. We present the seventh reported case with successful esophagoesophagostomy obtained by magnetic compression of a long-gap EA type A without thoracotomy. PMID- 29796382 TI - Incidence of Self-esteem among Children Exposed to Sexual Abuse in Kenya. PMID- 29796383 TI - HaloDom: a new database of halophiles across all life domains. AB - Background: Halophilic organisms may thrive in or tolerate high salt concentrations. They have been studied for decades and a considerable number of papers reporting new halophilic species are being published every year. However, an extensive collection of these salt-loving organisms does not exist nowadays. Halophilic life forms have representatives from all three life domains, Archaea, Bacteria and Eukarya. The purpose of this study was to search for all documented halophilic species in the scientific literature and accommodate this information in the form of an online database. Results: We recorded more than 1000 halophilic species from the scientific literature. From these, 21.9% belong to Archaea, 50.1% to Bacteria and 27.9% to Eukaryotes. Our records contain basic information such as the salinity that a particular organism was found, its taxonomy and genomic information via NCBI and other links. The online database named "HaloDom" can be accessed at http://www.halodom.bio.auth.gr. Conclusions: Over the last few years, data on halophiles are growing fast. Compared to previous efforts, this new halophiles database expands its coverage to all life domains and offers a valuable reference system for studies in biotechnology, early life evolution and comparative genomics. PMID- 29796384 TI - The repeated emergence of asexuality, the hidden genomes and the role of parthenogenetic rare males in the brine shrimp Artemia. AB - The backbone of this endeavour consists of three major components as they appear in the title. My intention is to summarise, as explicitly as possible, both existing and novel data on the occurrence of parthenogenetic rare males assessing their role in conveying sets of genetic information between asexual strains and sexual Artemia species to and fro. Additionally, an assemblage of strong indications and evidence is quoted aiming to unravel possible scenarios of the repeated emergence of asexuality in the brine shrimp and its significance in evolutionary processes involved in speciation. PMID- 29796385 TI - pH sensors and ion Transporters: Potential therapeutic targets for acid-base disorders. AB - Regulation of pH is critical for physiological processes. Maintenance of acid base homeostasis is tightly regulated by the renal and respiratory systems. However, fluctuations in extracellular pH are also sensed by other organ systems. Ion transporter activity to modify the amount of acid (H+ and CO2) and bicarbonate (HCO3-) is therefore actively maintained within the kidney and lung. This review describes acid-base disorders (acidosis and alkalosis) and highlights the importance of pH sensors and ion transporters that may be potential therapeutic targets for treatment of acid-base disorders. Specifically, the renal pH sensors proline-rich tyrosine kinase-2 (Pyk2) and G-protein coupled receptor-4 (GPR4) are discussed here. PMID- 29796386 TI - Microbial wars: Competition in ecological niches and within the microbiome. AB - Many microbial communities live in highly competitive surroundings, in which the fight for resources determines their survival and genetic persistence. Humans live in a close relationship with microbial communities, which includes the health- and disease-determining interactions with our microbiome. Accordingly, the understanding of microbial competitive activities are essential at physiological and pathophysiological levels. Here we provide a brief overview on microbial competition and discuss some of its roles and consequences that directly affect humans. PMID- 29796387 TI - Decreasing cytosolic translation is beneficial to yeast and human Tafazzin deficient cells. AB - Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase Tafazzin (TAZ). Loss-of-function mutations in the TAZ gene are responsible for the Barth syndrome (BTHS), a rare X-linked cardiomyopathy, presumably because of a diminished OXPHOS capacity. Herein we show that a partial inhibition of cytosolic protein synthesis, either chemically with the use of cycloheximide or by specific genetic mutations, fully restores biogenesis and the activity of the oxidative phosphorylation system in a yeast BTHS model (taz1Delta). Interestingly, the defaults in CL were not suppressed, indicating that they are not primarily responsible for the OXPHOS deficiency in taz1Delta yeast. Low concentrations of cycloheximide in the picomolar range were beneficial to TAZ-deficient HeLa cells, as evidenced by the recovery of a good proliferative capacity. These findings reveal that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of BTHS. This in turn, identifies cytosolic translation as a potential therapeutic target for the treatment of this disease. PMID- 29796389 TI - Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor. AB - Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune system work in concert to reduce C. albicans overgrowth through competition and modification of the growth environment. Here, we report that Escherichia coli (strain MG1655) outcompetes and kills C. albicans (strain SC5314) in vitro. We find that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity. PMID- 29796388 TI - Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK. AB - Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Adaptive regrowth is especially noticeable with short lived strains, including those defective for SNF1, the homolog of mammalian AMP activated protein kinase (AMPK). SNF1 becomes active in response to multiple environmental stresses that occur in chronologically aging cells, including glucose depletion and oxidative stress. SNF1 is also required for the extension of chronological lifespan (CLS) by caloric restriction (CR) as defined as limiting glucose at the time of culture inoculation. To identify specific downstream SNF1 targets responsible for CLS extension during CR, we screened for adaptive regrowth mutants that restore chronological longevity to a short-lived snf1? parental strain. Whole genome sequencing of the adapted mutants revealed missense mutations in TPR motifs 9 and 10 of the transcriptional co-repressor Cyc8 that specifically mediate repression through the transcriptional repressor Mig1. Another mutation occurred in MIG1 itself, thus implicating the activation of Mig1-repressed genes as a key function of SNF1 in maintaining CLS. Consistent with this conclusion, the cyc8 TPR mutations partially restored growth on alternative carbon sources and significantly extended CLS compared to the snf1? parent. Furthermore, cyc8 TPR mutations reactivated multiple Mig1-repressed genes, including the transcription factor gene CAT8, which is responsible for activating genes of the glyoxylate and gluconeogenesis pathways. Deleting CAT8 completely blocked CLS extension by the cyc8 TPR mutations on CLS, identifying these pathways as key Snf1-regulated CLS determinants. PMID- 29796390 TI - Advance care planning in life-threatening pulmonary disease: a focus group study. AB - Advance care planning (ACP) is a communication process for mapping a patient's wishes and priorities for end-of-life care. In preparation for the introduction of ACP in Norway, we wanted to explore the views of Norwegian pulmonary patients on ACP. We conducted four focus group interviews in a Norwegian teaching hospital, with a sample of 13 patients suffering from chronic obstructive pulmonary disease, lung cancer or lung fibrosis. Analysis was by systematic text condensation. Participants' primary need facing end-of-life communication was "the comforting safety", implying support, information and transparency, with four underlying themes: 1) provide good team players; 2) offer conversations with basic information; 3) seize the turning point; and 4) balance transparency. Good team players were skilled communicators knowledgeable about treatment and the last phase of life. Patients preferred dialogues at the time of diagnosis and at different "turning points" in the disease trajectory and being asked carefully about their needs for communication and planning. Transparency was important, but difficult to balance. ACP for patients with life-threatening pulmonary disease should rest upon an established patient-doctor/nurse relationship and awareness of turning points in the patient's disease progression. Individually requested and tailored information can support and empower patients and their relatives. PMID- 29796392 TI - Early Implanon Discontinuation and Associated Factors among Implanon User Women in Debre Tabor Town, Public Health Facilities, Northwest Ethiopia, 2016. AB - Background: Implanon discontinuation closely related to higher rates of overall fertility rate, unwanted pregnancies, and induced abortion. This might have social and economic consequences. In Ethiopia the magnitude of early Implanon discontinuation and contributing factors is not well studied. Objective: To assess early Implanon discontinuation and associated factors among Implanon user women in Debre Tabor town, 2016. Methods: A facility based cross-sectional study was conducted from May 1 to August 2016 through face-to-face interview. A total of 449 Implanon user women were selected by systematic random sampling technique. Epi Info version 7 and SPSS version 20 were used for data entry and analysis, respectively. Factors associated with early Implanon discontinuation were analyzed using binary and multivariable logistic regression model. Variables with p value of <0.05 and 95% confidence interval were considered as statistically significant. Results: The overall proportion of early Implanon discontinuation among mothers was 65 % (95%, CI: 60.4%-69.5%). Having no children (AOR = 2.0, 95% CI = [1.3-4.5]), being not counseled for possible side effects (AOR = 1.50, 95% CI = [1.1-3.4]), having no appointment for follow-up (AOR = 2.6, 95% CI = [1.2 4.3]), and having developing side effects (AOR = 1.7, 95% CI = [1.5-4.4]) were found to be statistically significant factors associated with early Implanon discontinuation. Conclusion and Recommendation: Early Implanon discontinuation among mothers was found to be high. Hence, counseling about Implanon side effects and appointment for follow-up of Implanon users should be made to increase Implanon retention. PMID- 29796391 TI - Dynamic hyperinflation during the 6-min walk test in severely asthmatic subjects. AB - We tested the hypothesis that dynamic hyperinflation develops in severe asthmatic subjects during exercise. Changes in inspiratory capacity (IC) were measured during the 6-min walk test (6MWT) in severe asthmatic subjects compared with chronic obstructive pulmonary disease (COPD) subjects with a similar degree of bronchial obstruction. We assessed whether changes in IC were associated with changes in dyspnoea perception. 27 severe asthmatic subjects (10 males and 17 females) and 43 COPD subjects (35 males and eight females) were recruited. The two groups performed similarly in the 6MWT (p=0.90). At the end of the test, the Borg score increased significantly in both groups (mean difference: for asthmatic subjects 1.7+/-1.6; p<0.0001; for COPD subjects 3.1+/-1.9; p<0.0001). IC measured at the beginning of 6MWT was not different between groups (2.25+/-0.47 L in asthmatic subjects versus 2.38+/-0.60 L in COPD subjects; p=0.32) and decreased in both groups (mean difference: for asthmatic subjects 0.160 L; p=0.02; for COPD subjects 0.164 L; p<0.0001). However, changes in IC were significantly associated with changes in the Borg score in the COPD group (r2=0.17; p=0.006), but not in the asthma group (r2=0.06; p=0.20). In severe asthmatic subjects, IC significantly drops during the 6MWT to the same extent as COPD subjects with a similar degree of lung impairment, indicating the development of dynamic hyperinflation. Contrary to COPD, in asthmatic subjects the occurrence of dynamic hyperinflation was not associated with changes in dyspnoea perception. PMID- 29796393 TI - The Role of Private Health Sector for Tuberculosis Control in Debre Markos Town, Northwest Ethiopia. AB - Background: Tuberculosis has been declared to be a global epidemic. Despite all the effort, only less than half the annual estimated cases are reported by health authorities to the WHO. This could be due to poor reporting from the private sector. In Ethiopia, tuberculosis has also been a major public health problem. The aim of this study was to assess the role of the private health sector in tuberculosis control in Debre Markos. Methods: An institution based cross sectional descriptive study was carried out in private health facilities. A total of 260 tuberculosis suspects attending the private clinics were interviewed. Focus group discussion, checklist, and structured questionnaire were used. Results: Majority of the private clinics were less equipped, poorly regulated, and owned by health workers who were self-employed on a part-time basis. Provider delay of 4 and more months was significantly associated higher likelihood of turning to a private provider (OR = 2.70, 95% CI = (1.20, 6.08)). Conclusions and Recommendations: There is significant delay among tuberculosis patients. Moreover, there is poor regulation of the private health sector by public health authorities. The involvement of the private sector in tuberculosis control should be limited to identification and refer to tuberculosis cases and suspects. PMID- 29796395 TI - Shewanella putrefaciens: An Emerging Cause of Nosocomial Pneumonia. AB - Gram-negative infections are a rising concern faced by the medical community. Approximately 30% of nosocomial bloodstream infections in intensive care units in the United States are caused by these gram-negative species. Emergence of multidrug-resistant organisms further complicate this issue. In this article, we report a case of an 84-year-old Caucasian male who was diagnosed with Shewanella pneumonia treated with cefepime with minimal to no improvement in his symptoms. To the best of our knowledge, this is the third reported case of Shewanella putrefaciens nosocomial pneumonia and first case of bacteremia secondary to pneumonia by Shewanella putrefaciens. PMID- 29796394 TI - Synthesis of graphene oxide-quaternary ammonium nanocomposite with synergistic antibacterial activity to promote infected wound healing. AB - Background: Bacterial infection is one of the most common complications in burn, trauma, and chronic refractory wounds and is an impediment to healing. The frequent occurrence of antimicrobial-resistant bacteria due to irrational application of antibiotics increases treatment cost and mortality. Graphene oxide (GO) has been generally reported to possess high antimicrobial activity against a wide range of bacteria in vitro. In this study, a graphene oxide-quaternary ammonium salt (GO-QAS) nanocomposite was synthesized and thoroughly investigated for synergistic antibacterial activity, underlying antibacterial mechanisms and biocompatibility in vitro and in vivo. Methods: The GO-QAS nanocomposite was synthesized through amidation reactions of carboxylic group end-capped QAS polymers with primary amine-decorated GO to achieve high QAS loading ratios on nanosheets. Next, we investigated the antibacterial activity and biocompatibility of GO-QAS in vitro and in vivo. Results: GO-QAS exhibited synergistic antibacterial activity against bacteria through not only mechanical membrane perturbation, including wrapping, bacterial membrane insertion, and bacterial membrane perforation, but also oxidative stress induction. In addition, it was found that GO-QAS could eradicate multidrug-resistant bacteria more effectively than conventional antibiotics. The in vitro and in vivo toxicity tests indicated that GO-QAS did not exhibit obvious toxicity towards mammalian cells or organs at low concentrations. Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and promoted infected wound healing in vivo. Conclusions: The GO-QAS nanocomposite exhibits excellent synergistic antibacterial activity and good biocompatibility both in vitro and in vivo. The antibacterial mechanisms involve both mechanical membrane perturbation and oxidative stress induction. In addition, GO-QAS accelerated the healing process of infected wounds by promoting re-epithelialization and granulation tissue formation. Overall, the results indicated that the GO-QAS nanocomposite could be applied as a promising antimicrobial agent for infected wound management and antibacterial wound dressing synthesis. PMID- 29796396 TI - Trichobezoar-Induced Heartburn in a Teenage Girl: A Case Report. AB - One of the most commonly encountered medical problems affecting all age groups in health care is abdominal pain. There are many surgical and medical causes behind this symptom; however, a rare cause of abdominal pain and other unspecific abdominal complaints are gastric bezoars. Gastric bezoars are defined as the accumulation of undigested or partially digested foreign materials in the stomach. They are typically found incidentally during upper endoscopy. Patients may present with abnormal behavior or eating disorders such as pica. Therefore, proper history taking and establishing a good rapport with the patient play a key role in diagnosis. We present a case of trichobezoar-induced heartburn in an 18 year-old female. In this article, we will discuss the types, risk factors, clinical picture, diagnosis, and treatment of this condition. PMID- 29796397 TI - Thyroid Storm Presenting as Psychosis. AB - Thyroid storm is a life-threatening endocrine emergency with an incidence rate of 1% to 2%. It is a systemic condition of excessive thyroid hormone production and release leading to thermoregulatory, adrenergic, neuropsychiatric, cardiovascular, and abdominal manifestations. Although it is a rare condition, it carries a significant mortality rate. Hence, knowing the common and uncommon presentations of thyroid storm is important for its prompt diagnosis and treatment. In this article, we present an unusual case of a young woman who presented with psychosis as the manifesting symptom of thyroid storm. She did not respond adequately to conventional medical treatment, requiring plasmapheresis and a definitive thyroidectomy, which ultimately led to the return of patient's baseline mental status and a dramatic recovery. PMID- 29796398 TI - Outcomes in the Orthopaedic Sports Medicine Fellowship Match, 2010-2017. AB - Background: Sports medicine is one of the most competitive fellowships in orthopaedic surgery. Despite its popularity, fellowship applicants have limited understanding of the orthopaedic sports medicine fellowship match process. Purpose: To define key outcomes in the orthopaedic sports medicine fellowship match, including the overall match rate, number of programs filled, and number of applicants ranked by programs that filled between 2010 and 2017. Study Design: Cross-sectional study. Methods: This study utilized data regarding the orthopaedic sports medicine fellowship match collected by the American Orthopaedic Society for Sports Medicine (AOSSM) from 2010 through 2017. Applicant data included number of applicants, number of matched and unmatched applicants, and percentage of applicants matching into their top choices. Fellowship program data included number of programs participating in the match and number of applicants ranked by filled and unfilled programs. Results: Between 2010 and 2017, the mean number of orthopaedic sports medicine fellowship applicants was 244.8. On average, 92.0% of applicants matched into a fellowship program. The mean number of programs participating in the fellowship match was 92.9, with a mean of 219.9 accredited positions and 5.4 nonaccredited positions. Over the time period studied, a mean of 75.8% of programs matched all available positions. Programs that matched fully ranked 9.0 applicants per position, on average, compared with a mean of 6.5 applicants ranked per position among programs that did not fully match (P = .0016). Conclusion: From 2010 to 2017, the number of applicants, positions available, overall match rate, and number of programs participating in the orthopaedic sports medicine fellowship match have remained consistent. The mean number of applicants per position ranked by fully matched fellowship programs was 9.0 compared with a mean of 6.5 applicants per position ranked by programs that did not fully match. These data may be helpful as we look to the future of orthopaedic sports medicine fellowship positions and the match process. In addition, this study reveals characteristics that divide sports medicine fellowship programs that fully match from those that do not. Applicants and/or fellowship program directors may utilize this information to modify their approach to the match process going forward. PMID- 29796399 TI - Bacterial Contamination of a Marking Pen in Anterior Cruciate Ligament Reconstruction. AB - Background: A sterile surgical marking pen is commonly used during anterior cruciate ligament reconstruction (ACLR) to outline the proposed skin incision and then to mark the graft during preparation. Once in contact with the skin, the pen is a potential source of bacterial transmission and subsequent infections after ACLR. Purpose/Hypothesis: The purpose of this study was to assess whether the skin marking pen is a fomite for contamination during arthroscopic ACLR. We hypothesized that there would be a difference in the rate of culture-positive pens between control pens and the study pens used to delineate the proposed skin incision. Study Design: Controlled laboratory study. Methods: Twenty surgical marking pens were collected prospectively from patients undergoing ACLR over a 12 month period. All patients underwent standard preoperative sterile preparation and draping procedures. Proposed incisions were marked with a new sterile pen, and the pen tip was immediately sent for a 5-day inoculation in broth and agar. Negative controls (unopened new pen) and positive controls (used to mark the skin incisions preoperatively) were also cultured. Additionally, blank culture dishes were observed during the growth process. All pens were removed from the surgical field before incision, and new marking pens were used when needed during the procedure. Results: Three of the 20 study pens (15%) demonstrated positive growth. All 3 pens grew species of Staphylococcus. None of the negative controls demonstrated growth, 6 of the 12 positive controls showed growth, and none of the blank dishes exhibited growth. Conclusion: This study found a 15% rate of surgical marking pen contamination by Staphylococcus during ACLR. It is recommended that the skin marking pen not be used for any further steps of the surgical case and be discarded once used. Clinical Relevance: Infections after ACLR are rare but may result in significant morbidity, and all measures to reduce them should be pursued. Surgeons performing ACLR should dispose of the surgical marking pen after skin marking and before intraoperative use such as graft markup. PMID- 29796400 TI - Patient-Related Risk Factors for Infection Following Ulnar Nerve Release at the Cubital Tunnel: An Analysis of 15,188 Cases. AB - Background: Although cubital tunnel release is a commonly performed orthopaedic procedure, the overall incidence of and independent risk factors for infection largely remain undefined in the current literature. Purpose: To establish the rate of postoperative infection after isolated cubital tunnel release and define relevant patient-related risk factors. Study Design: Case-control study; Level 3. Methods: All Medicare-insured patients undergoing ulnar nerve decompression at the cubital tunnel from 2010 through 2012 were identified. A multivariate binomial logistic regression analysis was utilized to evaluate the impact of patient-related risk factors for postoperative infection. Results: A total of 330 (2.17%) postoperative infections were identified in 15,188 cases. The majority (87%) were managed nonoperatively, while 13% required surgical debridement. The most significant risk factors for infection included hemodialysis use (odds ratio [OR], 2.47), chronic anemia (OR, 2.24), age <65 years (OR, 2.08), tobacco use (OR, 1.65), morbid obesity (OR, 1.53), inflammatory arthritis (OR, 1.43), depression (OR, 1.36), hyperlipidemia (OR, 1.33), male sex (OR, 1.32), and chronic lung disease (OR, 1.29). Conclusion: The present study was adequately powered to determine numerous patient-related risk factors for infection following cubital tunnel release. PMID- 29796401 TI - Learning From Failure in Cartilage Repair Surgery: An Analysis of the Mode of Failure of Primary Procedures in Consecutive Cases at a Tertiary Referral Center. AB - Background: As the number of cartilage restoration procedures is increasing, so is the number of revision procedures. However, there remains limited information on the reasons for failure of primary cartilage restoration procedures. Purpose: To determine the common modes of failure in primary cartilage restoration procedures to improve surgical decision making and patient outcomes. Study Design: Case series; Level of evidence, 4. Methods: Patients who presented for revision after failed cartilage repair surgery were evaluated for factors contributing to failure of the primary procedure. All revision cases performed by a single surgeon at a tertiary center for failed cartilage restoration over a 6 year time frame were identified. In all cases, the medical records, preoperative radiographs, and magnetic resonance imaging scans were reviewed by 2 experienced cartilage surgeons. The cause for failure was categorized as malalignment, meniscal deficiency, graft or biologic failure, or instability. Univariate and descriptive statistics regarding patient demographics, index procedure, lesion location and size, and mechanism of failure were analyzed. Results: A total of 59 cases in 53 patients (32 male, 21 female) met the inclusion criteria. The mean patient age at the time of revision was 27.6 years, and the mean body mass index was 28.4 kg/m2. Failed index surgical procedures included 35 microfractures (59%), 12 osteochondral allograft transplantations (20%), 10 osteochondral autograft transfers (17%), 2 nonviable osteochondral allografts (3%), and 2 particulated juvenile chondral allografts (3%). The mean lesion size was 4.4 cm2. Reasons for failure included 33 cases with untreated malalignment (56%), 16 with graft failure (27%), 11 with untreated meniscal deficiency (19%), and 3 with untreated instability (5%); 4 cases demonstrated multiple reasons for failure. Conclusion: The most commonly recognized reason for failure was untreated malalignment. While biologic and graft failures will occur, the majority of failures were attributed to untreated background factors such as malalignment, meniscal deficiency, and instability. The stepwise approach of considering and addressing alignment, meniscal volume, and stability remains essential in cartilage restoration surgery. PMID- 29796402 TI - Self-reported Mental Disorders Negatively Influence Surgical Outcomes After Arthroscopic Treatment of Femoroacetabular Impingement. AB - Background: Femoroacetabular impingement (FAI) is responsible for hip pain and dysfunction, and surgical outcomes depend on multiple factors. The presence of mental disorders negatively influences outcomes of multiple orthopaedic conditions, although the impact on FAI surgery is unclear. Hypothesis: The authors hypothesized that a preoperative self-reported history of mental disorders would negatively influence patient-reported outcome measures after FAI surgery. Study Design: Cohort study; Level of evidence, 3. Methods: A matched cohort study was performed by reviewing a prospectively collected database of cases of arthroscopic management of FAI with a single surgeon over a 2-year period. Demographics and radiographic parameters were recorded for all patients. Patients completed the Hip Outcome Score-Activity of Daily Living Subscale (HOS ADL), Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), and modified Harris Hip Score (mHHS) prior to surgery and 2 years after surgery. Unpaired and paired t tests were used to compare results between and within cohorts at baseline and follow-up. Statistical significance was defined as P < .05. Results: The cohort included 301 patients, with 75 and 226 patients reporting and not reporting a history of mental disorders, respectively. Before treatment, all patient-reported outcome measures were significantly lower among patients reporting a history of mental disorders (P < .01 for HOS-ADL, HOS-SSS, and mHHS). Patients in both groups demonstrated significant improvements (P < .0001) in HOS-ADL, HOS-SSS, and mHHS when preoperative outcome measures were compared with follow-up. Patients with reported mental disorders had significantly lower scores after surgery as compared with patients without mental disorders (P < .0001 for HOS-ADL, HOS-SSS, and mHHS). Conclusion: The presence of a reported mental disorder is associated with lower patient-reported outcomes before and after surgical management of FAI. Statistically significant and clinically relevant improvements were observed for patients who reported mental disorders. The magnitude of these improvements was not as large as that for an age- and sex-matched control group without a self reported mental disorder. PMID- 29796403 TI - Emerging Applications of Optical Coherence Tomography Angiography (OCTA) in neurological research. AB - Purpose: To review the clinical and research value of optical coherence tomography angiography (OCTA) in the field of neurology. Methods: Current literature involving OCTA were reviewed through PubMed using the search terms "optical coherence tomography angiography", with "multiple sclerosis", "Alzheimer's disease", "optic neuropathy", or other closely-related terms. Results: OCTA has been applied in research to advance our understanding of the pathobiology of neurological disorders. OCTA-derived blood flow and vessel density measures are altered in multiple sclerosis (MS), Alzheimer's disease (AD), and various optic neuropathies (ON) in varying regions of the posterior segment vasculature of the eye. These emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological disorders. Conclusion: OCTA may be beneficial for neurological research. Additional investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders. PMID- 29796404 TI - Relative peripheral refraction across 4 meridians after orthokeratology and LASIK surgery. AB - Background: To characterize the axial and off-axis refraction across four meridians of the retina in myopic eyes before and after Orthokeratology (OK) and LASIK surgery. Methods: Sixty right eyes with a spherical equivalent (M) between 0.75 to - 5.25 D (cylinder <- 1.00 D) underwent LASIK (n = 26) or OK (n = 34) to treat myopia. Axial and off-axis refraction were measured with an open-field autorefractometer before and after stabilized treatments. Off-axis measurements were obtained for the horizontal (35 degrees nasal and temporal retina) and vertical (15 degrees superior and inferior retina) meridians, and for two oblique directions (45-225 degrees and 135-315 degrees ) up to 20 degrees of eccentricity. The refractive profile was addressed as relative peripheral refractive error (RPRE). Results: OK and LASIK post-treatment results showed an increase of myopic relative refraction at several eccentric locations. At the four meridians evaluated, the M component of the pre-treatment RPRE values was not statistically different (p > 0.05) from the post-treatment RPRE within 30 degrees and 20 degrees of the central visual field after LASIK and OK, respectively. These results demonstrated that the treatment zone warrants an optimal central field of vision. Conclusions: The present study gives an overview of RPRE after refractive corneal reshaping treatments (OK and LASIK) across vertical, horizontal and two oblique meridians together. This allows a 3D representation of RPRE at the retina and shows that the myopic shift induced by both treatments is more relevant in horizontal directions. PMID- 29796406 TI - Trends in Geriatrics Graduate Medical Education Programs and Positions, 2001 to 2018. AB - : It is no secret that the average age of the U.S. population is increasing, and this has special significance for the U.S. health care system. The number of individuals above 65 years old is predicted to increase 55% by 2030, and all the while, there is a looming physician shortage, one especially relevant for Geriatricians. Therefore, current Geriatricians must have objective information to assess the past, present, and future state of this important specialty. However, little literature exists regarding the recent changes in Geriatrics related graduate medical education programs. In the present study, we use data from the Accreditation Council of Graduate Medical Education, to characterize quantitative trends in Geriatrics graduate medical education between academic years 2001-2002 and 2017-2018. We find that, when Hospice/Palliative Care is excluded, Geriatrics-related graduate medical education programs have grown by just 1.1% when adjusting for population growth. There are 58 fewer total filled Geriatrics and Geriatric Psychiatry positions in 2017-2018 than there were in 2001-2002, a population-adjusted decline of 23.3%. Our results confirm the growing notion that the Geriatrics specialty may need to alter its approach toward professional supply, if it is to meet the growing health care demands of an aging U.S. POPULATION: PMID- 29796405 TI - Evaluation of a Community-Based Program That Integrates Joyful Movement Into Fall Prevention for Older Adults. AB - Background: Despite the development of evidence-based fall-prevention programs, there remains a need for programming that will engage older adults in real-world settings. Objective: This study aimed to evaluate a community-based group program that integrates joyful movement into fall prevention. The curriculum emphasizes a positive experience of movement, cultivating a healthy body image, and retraining of biomechanics. Design: Program evaluation was conducted using a one-group pre post test study design. Key outcomes were functional balance and confidence. Qualitative feedback was gathered at the final class sessions. Results: Two hundred fifteen older adults enrolled at four sites over the period from 2010 to 2014. Among 86 participants who provided feedback, most credited the program for an increased sense of optimism and/or confidence (70%), and better walking ability (50%). Among 102 participants who completed both initial and final assessments, there was evidence of significant improvements on the Functional Reach Test (d = .60, p < .001) and Modified Falls Efficacy Scale (d = .17, p < .001). Conclusion: A joyful movement curriculum is acceptable to older participants, and they show improvements in functional balance and confidence. Future research should examine whether the positive changes encouraged by joyful movement lead to lasting reductions in fall risk and additional health benefits. PMID- 29796407 TI - Gender Differences in Withdrawing Infants. AB - Objective. To assess gender differences in infants diagnosed with neonatal abstinence syndrome at the Cabell Huntington Hospital in Huntington, West Virginia. Methods. This is a single-site retrospective chart review involving 97 infants born treated for neonatal abstinence syndrome at the Cabell Huntington Hospital between April and December 2015. Data were obtained from electronic medical records using a secure online survey tool designed using Qualtrics. Maternal demographics and drug screenings were collected. Infant information was collected for the first 7 days of life including withdrawal symptoms, treatment, and growth parameters. These data were analyzed based on gender, male (N = 62) and female (N = 35), to assess any gender differences among the infants. Results. No significant differences were found regarding birth weight, length, and gestational age between male and female infants. Differences among the percentage of symptoms experienced were found with females experiencing a greater percentage of symptoms affecting the autonomic nervous system compared with males. Significant differences in head circumference were found in these infants; females were found to have a greater head circumference at time of birth compared with males (P = .003), whereas at time of discharge head circumference was greater in males than in females (P = .035). Conclusion. Differences in symptoms, physical characteristics, and methadone treatment were found between male and female infants diagnosed with neonatal abstinence syndrome at the Cabell Huntington Hospital during 2015. Further studies are needed to assess both the short- and long-term effects of antenatal drug abuse. PMID- 29796408 TI - Breastfeeding Concerns and Their Management: One-Year Experience in a Physician Run Lactation Clinic. PMID- 29796410 TI - Faraday forcing of high-temperature levitated liquid metal drops for the measurement of surface tension. AB - In this work, a method for the measurement of surface tension using continuous periodic forcing is presented. To reduce gravitational effects, samples are electrostatically levitated prior to forcing. The method, called Faraday forcing, is particularly well suited for fluids that require high temperature measurements such as liquid metals where conventional surface tension measurement methods are not possible. It offers distinct advantages over the conventional pulse-decay analysis method when the sample viscosity is high or the levitation feedback control system is noisy. In the current method, levitated drops are continuously translated about a mean position at a small, constant forcing amplitude over a range of frequencies. At a particular frequency in this range, the drop suddenly enters a state of resonance, which is confirmed by large executions of prolate/oblate deformations about the mean spherical shape. The arrival at this resonant condition is a signature that the parametric forcing frequency is equal to the drop's natural frequency, the latter being a known function of surface tension. A description of the experimental procedure is presented. A proof of concept is given using pure Zr and a Ti39.5Zr39.5Ni21 alloy as examples. The results compare favorably with accepted literature values obtained using the pulse-decay method. PMID- 29796409 TI - Cognitive training for freezing of gait in Parkinson's disease: a randomized controlled trial. AB - The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks. The primary outcome was percentage of time spent frozen during a Timed Up and Go task, assessed both on and off dopaminergic medications. Secondary outcomes included multiple neuropsychological and psychosocial measures. A full analysis was first conducted on all participants randomized, followed by a sample of interest including only those who had objective FoG at baseline, and completed the intervention. Sixty-five patients were randomized into the study. The sample of interest included 20 in the CT group and 18 in the active control group. The primary outcome of percentage time spent frozen during a gait task was significantly improved in the CT group compared to active controls in the on-state. There were no differences in the off-state. Patients who received CT also demonstrated improved processing speed and reduced daytime sleepiness compared to those in the active control. The findings suggest that CT can reduce the severity of FoG in the on-state, however replication in a larger sample is required. PMID- 29796411 TI - Optimizing Live Kidney Donor Workup: A Decision Analysis Approach. AB - Background: Screening potential live kidney donors is an intense process for both candidates and the healthcare system. It is conventionally implemented using a standard generic protocol. Efficiencies in this process could potentially be achieved using personalized protocols that are optimized for a given candidate. Aim: To create personalized protocols (by age, sex, and paired exchange status) and evaluate them relative to the standard generic protocol. Methods: Two personalized protocols were created. One sequenced tests according to probability (high to low) of excluding a given candidate. The other sequenced tests according to the expected cost (low to high) per exclusion. Test costs and exclusion probabilities were extracted predominantly from Australian sources. These were integrated into a decision analysis incorporating Markov processes. This estimated the expected financial cost and expected number of tests performed to exclude an ineligible candidate in the standard generic and personalized protocols. Results: The standard generic protocol consistently ranked poorest in terms of expected costs and expected tests per exclusion across all ages, sexes, and paired exchange status. Compared with the most efficient personalized protocol, the standard generic protocol was on average A$1767.49 more expensive and required 3.53 more tests. Conclusions: Personalized protocols enhance the ability of a kidney transplant unit to effectively exclude live kidney donor candidates more quickly and cost effectively compared with the conventional standard generic protocol. PMID- 29796412 TI - Adult Living Donor Liver Transplantation for Patients With Portal Vein Thrombosis: A Single-center Experience. AB - Background: Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) is associated with several technical challenges for its complicated procedures and poor outcomes. Some institutions still consider preexisting PVT as a relatively contraindication for LDLT. Methods: Between April 2010 and May 2016, 129 adults underwent LDLT at our institution, and 28 (21.7%) of whom had preexisting PVT. Portal vein thrombosis was diagnosed using preoperative imaging techniques and intraoperative findings. The characteristics and outcomes of the cases were retrospectively evaluated. Results: The type of PVT included Yerdel grade 1 in 21 (75.0%) cases, grade 2 in 3 (10.7%) cases, and grade 3 in 4 (14.3%) cases. There were no cases of Yerdel grade 4 PVT. After removing thrombus inside the vessel, we performed simple portal vein anastomosis in 25 (89.3%) cases, patch technique with vascular graft in 1 case (3.6%), and an interposition technique with vascular graft in 2 cases (7.1%). Compared with the non-PVT group, cold ischemic time was longer (P = 0.012) and the rate of postoperative PVT was higher (P = 0.001) in PVT group. In the comparison between the recipient without and with postoperative PVT, the existence of preoperative PVT was the independent risk factor in the multivariate analysis (hazard ratio, 7.511; 95% confidence interval 1.382-40.820; P = 0.020). Conclusions: Although it had a technically complicated operation, LDLT could be safely performed in the patients with PVT in our institution. PMID- 29796413 TI - Factors Associated With Prolonged Warm Ischemia Time Among Deceased Donor Kidney Transplant Recipients. AB - Background: Prolonged warm ischemia time (WIT) is associated with graft failure and mortality, however less is known about factors associated with prolonged WIT. Methods: In a cohort of United States deceased donor kidney transplant recipients identified using the Scientific Registry of Transplant Recipients (Jan 2005-Dec 2013), we identified factors associated with prolonged WIT (defined as >= 30 minutes versus 10-30 minutes) using hierarchical multilevel models adjusting for center effect, and WIT as a continuous variable using multiple linear regression of log-transformed data. Results: Among 55 829 patients, potentially modifiable risk factors associated with prolonged WIT included increased recipient body mass index (BMI) (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.44-1.72 for BMI > 35), right donor kidney (OR, 1.14; 95% CI, 1.08-1.19), and a prolonged cold ischemic time (OR, 1.23; 95% CI, 1.13-1.33 for cold ischemia time > 24 hours). Transplanting a right kidney into an obese recipient further prolonged WIT (OR, 1.75; 95% CI, 1.55-1.98; for BMI > 35), increasing overall WIT by 11.0%. There was no correlation between median WIT for a given center and annual center transplant rate (pairwise correlation coefficient, 0.0898). Conclusions: In conclusion, several modifiable factors are associated with prolonged WIT and may represent strategies to improve WIT and subsequent posttransplant outcomes. PMID- 29796415 TI - Accessory Gallbladder Complicating Liver Transplantation. AB - Accessory gallbladder in a donor liver allograft is an uncommon anatomical finding that can complicate liver transplantation if unrecognized. This case describes a patient who underwent liver transplantation with a donor graft containing an accessory gallbladder that was obscured during transplantation; as a result, the patient experienced a prolonged postoperative course complicated by multiple readmissions for suspected biloma and intra-abdominal infection. The diagnosis of accessory gallbladder was not made until operative exploration several months after the initial transplant. Removal of the accessory gallbladder has led to resolution of clinical problems. PMID- 29796414 TI - Assessing Consensus Between UK Renal Clinicians on Listing for Kidney Transplantation: A Modified Delphi Study. AB - Background: It is well recognized that there is significant variation between centers in access to kidney transplantation. In the absence of high-grade evidence, it is unclear whether variation is due to patient case mix, other center factors, or individual clinician decisions. This study sought consensus between UK clinicians on factors that should influence access to kidney transplantation. Methods: As part of the Access to Transplantation and Transplant Outcome Measures project, consultant nephrologists and transplant surgeons in 71 centers were invited to participate in a Delphi study involving 2 rounds. During rounds 1 and 2, participants rated their agreement to 29 statements covering 8 topics regarding kidney transplantation. A stakeholder meeting was used to discuss statements of interest after the 2 rounds. Results: In total, 122 nephrologists and 16 transplant surgeons from 45 units participated in rounds 1 and 2. After 2 rounds, 12 of 29 statements reached consensus. Fifty people participated in the stakeholder meeting. After the stakeholder meeting, a further 4 statements reached agreement. Of the 8 topics covered, consensus was reached in 6: use of a transplant protocol, patient age, body mass index, patient compliance with treatment, cardiac workup, and use of multidisciplinary meetings. Consensus was not reached on screening for malignancy and use of peripheral Doppler studies. Conclusions: The Delphi process identified factors upon which clinicians agreed and areas where consensus could not be achieved. The findings should inform national guidelines to support decision making in the absence of high quality evidence and to guide areas that warrant future research. PMID- 29796416 TI - Endothelial Dysfunction in Steatotic Human Donor Livers: A Pilot Study of the Underlying Mechanism During Subnormothermic Machine Perfusion. AB - Background: Steatosis is a major risk factor for primary nonfunction in liver transplantations. Steatotic livers recover poorly from ischemia reperfusion injury, in part due to alterations in the microcirculation, although the exact mechanism is unclear. In this study, we tested if there were any alterations in the shear stress sensing Kruppel-like factor 2 (KLF2) and its likely downstream consequences in the ex vivo perfused human liver endothelium, which would imply perturbations in microcirculatory flow in macrosteatotic livers disrupts laminar flow to evaluate if this is a potential therapeutic target for steatotic livers. Methods: Using a subnormothermic machine perfusion system, 5 macrosteatotic and 4 nonsteatotic human livers were perfused for 3 hours. Flow, resistance, and biochemical profile were monitored. Gene expression levels of nitric oxide synthase 3 (eNOS), KLF2, and thrombomodulin were determined. Nitric oxide (NO) was measured in the perfusion fluid and activation of eNOS was measured with Western blotting. Results: Flow dynamics, injury markers, and bile production were similar in both groups. Kruppel-like factor 2 expression was significantly higher in nonsteatotic livers. Western blotting analyses showed significantly higher levels of activated eNOS in nonsteatotic livers, consistent with an increase in NO production over time. Macrosteatotic livers showed decreased KLF2 upregulation, eNOS activity, and NO production during machine perfusion. Conclusions: These results indicate a perturbed KLF2 sensing in steatotic livers, which aligns with perturbed microcirculatory state. This may indicate endothelial dysfunction and contribute to poor posttransplantation outcomes in fatty livers, and further studies to confirm by evaluation of flow and testing treatments are warranted. PMID- 29796418 TI - Role of MRCP in Diagnosing Biliary Anastomotic Strictures After Liver Transplantation: A Single Tertiary Care Center Experience. AB - Background: Biliary strictures (BS) are common complication after liver transplantation. We aimed to determine the accuracy of magnetic resonance cholagiopancreatography (MRCP) in diagnosing BS in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (endoscopic resonance cholagiopancreatography [ERCP] and/or percutaneous transhepatic cholangiography [PTC]). Methods: Retrospective chart review of 910 LTRs (July 2008 to April 2015) was performed, and a total of 39 patients with duct-to-duct anastomosis (22 males; 56.4%; mean age, 52.8 +/- 8.3 years) were included who had an MRCP followed by either ERCP and/or PTC within 4 weeks. A cholangiographic narrowing (on ERCP and/or PTC) that required balloon dilation and/or stent placement was considered a BS and was considered clinically significant if the intervention resulted in at least 30% improvement of bilirubin within 2 weeks. Sensitivity, specificity, accuracy, positive predictive values and negative predictive values of MRCP in diagnosing BS were calculated. Results: Magnetic resonance cholagiopancreatography showed anastomotic BS in 17 of 39 patients, and subsequent ERCP and/or PTC revealed a total of 25 BS (positive predictive value of 0.94). Nine BS on cholangiography (ERCP, 8; PTC, 1) were not detected on earlier MRCP (sensitivity, 0.64; 95% CI, 0.45-0.82); 2 were clinically significant BS and 6 of the remaining 7 had no improvement in their liver function test with biliary intervention. Thirteen LTRs had no BS on either modality (specificity, 0.93; 95% CI, 0.66-0.99). The negative predictive value of MRCP was 0.59 for cholangiographic BS. The overall accuracy of MRCP is 0.74 (exact 95% CI, 0.58-0.87). Inclusion of age, race, and alanine aminotransferase level improved the predictive value of MRCP (area under the curve = 0.94, 95% CI: 0.86-1.00). Conclusions: Magnetic resonance cholagiopancreatography has high specificity but low sensitivity in diagnosing cholangiographic BS in LTRs, although the predictive value further improved with inclusion of age, race, and alanine aminotransferase. Clinical significance of BS in LTRs not identified on MRCP is questionable because ERCP with intervention did not improve their liver function tests in the vast majority. PMID- 29796417 TI - Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study. AB - Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients. Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments. Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P <= 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP >=10, >=24, >=17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P <= 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P >= 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered. PMID- 29796419 TI - Liver Transplantation Without Venovenous Bypass: Does Surgical Approach Matter? AB - Background: The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era. Methods: Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques. Results: One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches. Conclusions: In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass. PMID- 29796420 TI - Single-Center Long-Term Analysis of Combined Liver-Lung Transplant Outcomes. AB - Background: Combined lung-liver transplantation (LLT) applies 2 technically challenging transplants in 1 patient with severe 2-organ failure. Methods: Institutional medical records and United Network for Organ Sharing database were queried for patients at our institution that underwent LLT from 2000 to 2016. Results: Twelve LLTs were performed from 2000 to 2016 including 9 male and 3 female recipients with a median age of 28.36 years. Indications for lung transplantation were cystic fibrosis (8), idiopathic pulmonary fibrosis (3), and pulmonary fibrosis secondary to hepatopulmonary syndrome (1). Indications for liver transplantation were cystic fibrosis (8), alcoholic cirrhosis (1), idiopathic cirrhosis (2), and alpha-1 antitrypsin deficiency (1). Median forced expiratory volume in 1 second at transplant was 27.8% (+/-20.38%), and mean Model for End-Stage Liver Disease was 10.5 (+/-4.68). Median hospital stay was 44.5 days. Seventy-five percent of recipients had 1+ new infection during their transplant hospitalization. Patients experienced 0.68 incidences of acute rejection per year with a 41.7% (95% confidence interval, 21.3%-81.4%) probability of freedom from rejection in the first-year. Patient survival was 100% at 30 days, 91.6% at 1 year, and 71.3% at 3 years. At the time of analysis, 7 of 12 patients were alive, of whom 3 survived over 8 years post-LLT. Causes of death were primary liver graft failure (1), bronchiolitis obliterans syndrome (2), and solid tumor malignancies (2). Conclusions: Our results indicate that LLT is associated with comparable survival to other LLT series and provides a granular assessment of infectious and rejection rates in this rare population. PMID- 29796421 TI - Cyclophosphamide for Refractory Acute Cellular Rejection After Lung Transplantation. AB - Background: Acute cellular rejection (ACR) is a major risk factor for chronic lung allograft dysfunction after lung transplantation. Acute cellular rejection can persist or recur despite augmentation of immunosuppression by conventional methods. There are limited therapeutic options in treating these recurrent and refractory ACRs. We describe our experience with cyclophosphamide therapy for recurrent and refractory ACR in lung transplant recipients. Methods: Six consecutive patients who were treated with cyclophosphamide for recurrent or refractory ACR were included in the series. The primary outcome measures were improvement in ACR score and forced expiratory volume at 1 second. Secondary outcome measures included adverse drug events including bone marrow suppression, gastrointestinal side effects, and infections. Results: Five of the 6 patients treated demonstrated complete resolution of ACR on follow-up biopsies. Acute cellular rejection score improved after cyclophosphamide treatment (P = 0.03). None of the patients had high grade (>=A3) ACR in the 3 months after cyclophosphamide administration. Cyclophosphamide had no effect on forced expiratory volume at 1 second trend or bronchiolitis obliterans score. All patients tolerated cyclophosphamide with minor gastrointestinal side effects, mild bone marrow suppression, and nonfatal infections that were amenable to treatment. Conclusions: Cyclophosphamide therapy is an option in treating recurrent and refractory ACR in patients who have failed conventional treatments. Cyclophosphamide is tolerated well without serious adverse drug events (ADE). PMID- 29796423 TI - Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes. AB - Aims: To assess neuronal depolarization evoked by autoantibodies in diabetic depression compared to depolarization evoked by autoantibodies in control patients. To determine whether a subset of severe (late-onset) diabetic complications may be mediated in part by toxic immunoglobulin light chains that may increase in diabetic nephropathy. Methods: Protein-A eluates from plasma of 21 diabetic depression patients and 37 age-matched controls were tested for depolarization in hippocampal or immature neurons. Subsets of depolarizing or non depolarizing autoantibodies were tested for neurite outgrowth inhibition in N2A neuroblastoma cells or the ability to modulate Ca2+ release in HL-1 atrial cardiomyocytes or in endothelial cells. The stability of depolarizing autoantibodies was investigated by heat treatment (56 degrees C * 30 minutes) or following prolonged exposure to the pro-protein convertase, furin. Gel filtration of active depolarizing autoantibodies was performed to determine the apparent molecular mass of peak neurotoxicity associated with the autoantibodies. Results: Diabetic depression (n = 21) autoantibodies caused significantly greater mean depolarization in neuroblastoma cells (P < 0.01) compared to autoantibodies in diabetic (n = 15) or non-diabetic (n = 11) patients without depression. Depolarizing autoantibodies caused significantly more (P=0.011) inhibition of neurite outgrowth in neuroblastoma cells than non-depolarizing autoantibodies (n = 10) and they evoked sustained, global intracellular Ca2+ release in atrial cardiomyocytes or in endothelial cells. A subset of older diabetic patients suffering with a cluster of nephropathy, non-ischemic cardiomyopathy and/or depression demonstrated the presence of stable light chain dimers having apparent MW of 46 kD and associated with peak neurotoxicity in neuroblastoma cells. Conclusion: These data suggest that autoantibodies in older adult diabetic depression cause long-lasting depolarization in hippocampal neurons including adult dentate gyrus neural progenitor cells. The autoantibodies may impair adult dentate gyrus neurogenesis associated with treatment-refractory depression via several mechanisms including suppression of neurite outgrowth, and alteration of membrane excitability. Stable, toxic light chain autoantibody components may contribute to a cluster of severe (late-onset) complications characterized by dysfunction in highly vascularized tissues. PMID- 29796422 TI - Autoantibodies in Human Diabetic Depression Inhibit Adult Neural Progenitor Cells In vitro and Induce Depressive-Like Behavior in Rodents. AB - Aim: Diabetic depression increases in association with microvascular complications. We tested a hypothesis that circulating autoantibodies having anti endothelial and anti-neuronal properties increase in subsets of diabetes with co morbid depression. Methods: Protein-A eluates from plasma of 20 diabetic depression patients and 30 age-matched controls were tested for effects on endothelial cell survival, neurite outgrowth in rat pheochromocytoma (PC12) cells, or process extension and survival in adult rat dentate gyrus neural progenitor cells. The protein-A eluates from depressed or non-depressed, diabetic patients were injected (via intracerebroventricular route) into mice and 7-10 days later behavioral tests (sucrose preference, and tail suspension tests) were conducted to determine whether the autoantibodies induced anhedonia or despair. Results: Diabetic depression (n=20) autoantibodies caused a significant inhibition of PC12 cell neurite outgrowth (P<0.001) or endothelial cell proliferation compared to autoantibodies in control, diabetic (n=20) or non diabetic (n=10) patients without depression. Process extension and survival in adult rat dentate gyrus neural progenitor cells was significantly reduced (P<0.001) by diabetic depression autoantibodies (n= 11) compared to the effects from similar concentrations (5-7 MUg/mL) of autoantibodies in diabetic (n=12) or non-diabetic patients without depression (n=7). Ten micromolar concentrations of Y27632, a selective Rho-Associated Protein Kinase (ROCK) inhibitor, significantly prevented (P<0.0001) neural progenitor cell process retraction induced by diabetes depression autoantibodies (n=5). Mice treated with diabetic depression autoantibodies (n=16 from two different patients' autoantibodies) exhibited significantly reduced (P=0.027) sucrose preference (anhedonia) compared to mice treated with diabetic control autoantibodies (n=16 from two different patients' autoantibodies). Conclusion: These data suggest that autoantibodies in a subset of older adult diabetic depression inhibit endothelial cell survival, and impair process extension and survival in adult dentate gyrus neural progenitor cells in vitro. PMID- 29796425 TI - Dyspnea in the Supine Position after Anterior Cervical Discectomy and Fusion. AB - Posterior occipitocervicothoracic fusion in a flexed position may cause dyspnea, and the onset of obstructive sleep apnea after anterior upper cervical fusion. However, there are no reports of dyspnea occurring after anterior lower cervical fusion. Here, we present an unusual case of dyspnea in the supine position after a C5-C6 anterior cervical discectomy and fusion. PMID- 29796424 TI - The Impact of Frailty on Postoperative Cardiopulmonary Complications in the Emergency General Surgery Population. AB - Background The burden of frail patients undergoing emergency general surgery (EGS) is increasing rapidly and this population is particularly susceptible to postoperative cardiopulmonary complications and mortality. We aimed to determine the association between frailty, as defined by the previously described modified frailty index (mFI), and postoperative respiratory complications (unplanned reintubation, pneumonia, and prolonged ventilation), cardiac complications (myocardial infarction and cardiac arrest), and mortality. We also sought to identify the most significant determinants of frailty in the highest risk patients based on the specific variables comprising the mFI. Methods We performed a retrospective observational analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Files from 2005 to 2015 identified 132,765 inpatients who underwent EGS. mFI scores were calculated for each patient. The effect of increasing frailty on unplanned reintubation, pneumonia, prolonged ventilation, myocardial infarction, cardiac arrest, and mortality was evaluated using bivariate analysis. Multivariable logistic regression was used to compare mFI with additional predictor variables including race, gender, physical status as defined by the American Society of Anesthesiologists, disseminated cancer, renal failure, smoking status, sepsis, wound presence/classification, dyspnea, and previous ventilator dependence. Results Unplanned reintubation, pneumonia, prolonged ventilation, myocardial infarction, cardiac arrest, and mortality were significantly associated with frailty, and the odds of each postoperative complication increased with increasing mFI score. Of the frailest patients (mFI >=3) that experienced cardiopulmonary complications or mortality, the variables of the mFI that contributed most to frailty were hypertension requiring medication and functional status before surgery. Conclusions A higher mFI score is associated with increased odds of postoperative cardiopulmonary complications and mortality in the EGS population. Specific variables of the mFI can also provide valuable information for assessing odds in the frailest patients undergoing EGS. PMID- 29796426 TI - The Modified Iliopubic Tract Repair-A Pain-Free Alternative. AB - Background The open preperitoneal repair offers the benefits of placing the mesh in the preferred position while avoiding the disadvantages of laparoscopic repair. Methods A total of 60 patients with bilateral inguinal hernias were randomized to undergo either the standard Lichtenstein meshplasty or the modified iliopubic tract repair in a teaching hospital. Outcomes measured were immediate postoperative pain, return to activity, and delayed neurological complications. Results Patients who underwent the iliopubic tract repair walked out of bed faster than the Lichtenstein group (6.3 hours vs 7.4 hours, p < 0.0001) and experienced significant lower pain as charted by visual analogue scale scores (3.28 vs 2.71 on day 1, 2.16 vs 1.71 on day 2, 1.92 vs 1.08 on day 3; p < 0.05). Delayed complications like chronic inguinal pain and numbness were not seen in the iliopubic tract group. However, this difference was not statistically significant ( p > 0.05). Conclusion The iliopubic tract repair offers an excellent alternative to the Lichtenstein meshplasty, and is associated with lower postoperative pain, earlier return to work, and lower delayed neurological complications. PMID- 29796427 TI - Using an introduction website to start a family: implications for users and health practitioners. AB - Donor insemination treatment offered in licensed clinics protects the donor, recipient and offspring both medically and legally. The Internet has opened up novel, unregulated ways of donating sperm through 'introduction websites' and social media forums. Broadly, three categories of women use introduction websites: those who want to have a child with no further involvement of the donor; those who wish to know the identity of the donor from the start; and those who intend to electively co-parent, that is, to bring up the child together with the donor/father. Donors may choose to donate through introduction websites for altruistic reasons and/or in order to have greater involvement with the child. There are some donors who are motivated by the prospect of a sexual encounter, advertising their preference for 'natural insemination' - i.e. via sexual intercourse or partial intercourse. When people make their own arrangements online, they may do so in the absence of clear, accurate information. This article, sets out some of the issues that recipients and donors ought to consider before embarking on unregulated sperm donation. PMID- 29796428 TI - Romanian Journal of Ophthalmology is indexed in PMC and PUBMED. More to come on the indexing processes soon. PMID- 29796429 TI - The role of Optical Coherence Tomography in optic neuropathies. AB - : Optical neuropathies are neuro-ophthalmologic disorders, the main symptoms of which are the decrease of visual acuity and the alteration of the color vision. Optical coherence tomography has been one of the most important innovations in ophthalmology, which offered the possibility to analyze specific structures of the retina. Optical coherence tomography performs in vivo, real-time, noncontact scanning and provides cross-sectional and volumetric images with a resolution approaching that of histology. Optical coherence tomography offers the opportunity to study neurological diseases in an objective and non-invasive manner. The measurements of retinal nerve fiber layer can be an objective measurement of nerve swelling or nerve atrophy. By analyzing the ganglion cell complex, optical coherence tomography can help detect early axonal damage and may predict the visual outcome. It can be useful for diagnosis and follow-up of optic nerve and chiasmal compressive diseases. Furthermore, optical coherence tomography is useful in patients with multiple sclerosis in distinguishing macular disease from optic neuritis and in monitoring the treatment. Multiple studies and clinical observations support the importance of optical coherence tomography in the diagnosis, treatment, and follow-up of optic neuropathies. ABBREVIATIONS: OCT = optical coherence tomography, VA = visual acuity, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, ON = optic neuropathy, NAION = non-arteritic ischemic anterior optic neuropathy, LHON = Leber hereditary optic neuropathy, RE = right eye, LE = left eye. PMID- 29796431 TI - Effect of sevoflurane preconditioning on light-induced retinal damage in diabetic rats. AB - Hyperglycemia and bright light are powerful stress agents that produce an enhanced retinal damage, when simultaneously acting on retina. Previous studies have shown that preconditioning with sevoflurane anesthesia offers a certain degree of protection to retinal cells against light damage. The objective of this study was to explore the effect of sevoflurane anesthetic preconditioning on a model of light-induced retinal degeneration in diabetic rats. Wistar rats that were randomly divided into four groups: control (rats exposed to photostress), group 1 (rats exposed to photostress and sevoflurane preconditioning), group 2 (diabetic rats exposed to photostress), group 3 (diabetic rats exposed to photostress and sevoflurane preconditioning) were used for this experiment. We recorded basal electroretinogram (ERG), at 36 h and 14 days after photostress and performed histological analysis of the retina. Results showed that sevoflurane has a protective effect on light-induced neuroretinal degeneration proved by significantly less variations of the ERG before and after photostress. Diabetes appears to increase the damaging effect of photostress on retina and attenuate the protection provided by sevoflurane preconditioning. PMID- 29796432 TI - Electrophysiologic evaluation of the visual pathway at different depths of sevoflurane anesthesia in diabetic rats. AB - Our study investigated the changes produced by diabetes on the visual pathway in a Wistar rat model. The impact of diabetes at 10 weeks after intraperitoneal streptozotocin (STZ) injection was evaluated through electrophysiological methods like visual evoked potentials (VEP) and electroretinogram (ERG). VEP and ERG were recorded simultaneously under different sevoflurane anesthetic depths. In all tested concentrations, sevoflurane affected the amplitude and latency of VEP and ERG component elements. With increasing anesthetic depths, sevoflurane increased the latencies of VEP N1, P1 and N2 peaks and ERG a- and b- waves in both control and diabetic animals. On the other hand, the amplitude of VEP showed enhancement in higher concentrations of sevoflurane, contrariwise to the drop of amplitude seen in the ERG. Diabetes additionally increased the latencies of VEP peaks and decreased the N1-P1 amplitude of the VEP when compared to control at the same anesthetic depth. The a- and b- waves were also delayed by diabetes at 10 weeks post-STZ diabetic induction, with the exception of highly profound anesthetic depth in which the result for the b wave were conflicting. We found a reduction in amplitude of the a-b wave in diabetic animals, when ERG was recorded under 6% and 8% sevoflurane concentration. In conclusion, neurophysiological studies like VEP and ERG are useful in the assessment of retinal and optic nerve dysfunctions produced by diabetes, yet considering the alterations that occur during anesthesia if this is used. PMID- 29796430 TI - Ocular implants-methods of ocular reconstruction following radical surgical interventions. AB - The main motivation of an ocular-orbital reconstruction after a radical surgical intervention (evisceration, enucleation) is represented by the psychological and socio-economic impact of such interventions on life conditions of patients. The current methods for ocular prosthesis are based on a new concept, which is nanotechnology, and its main objectives represent the reconstruction of the remaining orbital volume, reduction of postoperative complications and maintaining a satisfactory esthetical aspect. This review will discuss the numerous types of ocular implants that have been used throughout history as well as the most recent methods used by ophthalmic surgeons, also taking into consideration the advantages and disadvantages from a cosmetic, functional and short and long term postoperative complications point of view. PMID- 29796433 TI - Correlations between internal and external ocular factors and macular pigment optical density. AB - AIM: To assess the relationship between the macular pigment optical density and blue-light issued by computers, glare sensibility, with iris color, age, sex, or refractive errors. MATERIAL AND METHODS: 83 patients (166 eyes) were enrolled in a prospective observational study. They were divided into 2 groups: group 1 (study group) - computer using patients (time spent in front of the computer for minimum 8 hours per day, 5 days per week, 2 years) - 43 patients and group 2 (control group) - 40 patients. The following investigations were conducted in all the selected cases: visual acuity, refraction, biomicroscopy, measurement of the MPOD, glare sensitivity, assessment of eye color. RESULTS: 51.81% of the patients were included in group 1, while the rest, 48.19%, were in group 2. Thus, the MPOD had a mean value of (+/ -SD) 0.42+/ -0.13 (t = -1.08, p = 0.28) in group 1, and 0.44+/ -0.16 on the LE. The results showed a MPOD mean value of 0.51+/ - 0.16 in group 2 and 0.51+/ -0 .16. (t = 0.49, p = 0 .62) on the LE. 55.77% of the patients with light colored iris and 56.14% of those with dark iris had a low MPOD. CONCLUSIONS: The data from our study failed to illustrate a significant correlation between MPOD and blue-light issued by computers. Furthermore, a statistic significant relationship regarding iris color, refractive errors, glare, and MPOD was not observed. ABBREVIATIONS: L = lutein, Z = zeaxanthin, MZ = meso-zeaxanthin, AMD = age related macular degeneration, MPOD = macular pigment optical density, MP = macular pigment, HFP = Heterochromatic Flicker Photometry, RE = right eye, LE = left eye. PMID- 29796434 TI - Medical and legal point of view for low-vision patients. AB - The aim of the study was to highlight the medical and legal difficulties in framing low-vision patients for certification. We performed a retrospective observational study conducted from January 2013 to January 2016, on 63 patients with the mean age of 16.37+/-3.34 years, evaluated at the Ophthalmology Clinic from "Sf. Spiridon" Hospital, Iasi, in order to release a medical certificate required at the Expertise Board. The clinical parameters observed were visual acuity (VA) with correction, objective refraction (in Spherical Equivalent - SEq), intraocular pressure, slit lamp examination of the anterior pole, fundus examination, orthoptic eye exam, and ocular ultrasonography (in selected cases). The main causes for the decreased visual acuity found are refractive or strabic amblyopia determined by: high myopia (28.57%), esotropia (19.04%), astigmatism (17.46); congenital diseases - congenital nystagmus (12.69%), congenital cataract (7.93%), microphthalmia (7.93%); acquired diseases - retinopathy of prematurity (9.52%), optic nerve atrophy (7.93%), bandelette keratopathy (6.34); ocular trauma (7.93%). In 52.38% of the cases for the RE and 53.96% of the cases for the LE, decreased visual acuity was caused by an irreversible condition and could not be improved. Patients come every year for reevaluation in order to receive the medical certificate required at the Expertise Board. Evaluating the patient for a certificate for visual impairment is a time consuming process due to the high number of investigations necessary and, sometimes, difficult collaboration with the patient with associated general pathology. It also requires knowledge of frequently changing legislation to complete legal forms for patients with visual impairment. A medical certificate may now be issued with a validity of up to four years, given that certain diseases are irreversible and visual functional status does not change over time. PMID- 29796435 TI - Measuring the perceived quality of ophthalmology services in private organizations. A marketing perspective. AB - : Nowadays, the competition registered on the Romanian markets regarding the activity of private ophthalmology organizations has raised their interest in developing consumer-oriented strategies. The key factor that assures a differentiation as well as a competitive advantage is the service quality from a marketing perspective. OBJECTIVES: From a marketing perspective, service quality is measured as a perceived discrepancy between the consumers' expectations and was actually performed in health care services. The most widely and validated measurement is the SERVQUAL scale. However, a variety of SERVQUAL scales have been applied in different health care environments without taking into consideration the specialty of the health care service. Thus, the objective of this paper was to measure the service quality in the Romanian ophthalmology private organizations using the SERVQUAL measurement, by identifying the SERVQUAL dimensions, which register the highest and the lowest gap scores. MATERIALS AND METHODS: The instrument for data collection was the SERVQUAL self-administered questionnaire that consisted of 22 items measured on a 5-point Likert scale. The sample size encompassed 100 participants and the sampling technique was the snowball. The internal consistency, validity and the reliability of the SERVQUAL scale was determined by the Cronbach's alpha coefficients and factor analysis. The SERVQUAL questionnaire focused on 5 dimensions (tangibles, reliability, assurance, empathy and responsiveness) and each dimension, in its turn, was characterized by different items. RESULTS: The mean age of the participants was 49.52 years, with a mean income of 3031 Romanian Currency and the mean period of wearing eyeglasses was 5 years (+/-2). Further, there were 47% females and 53% males. The overall internal consistency of the SERVQUAL scale, as well as the dimensions' internal consistency were all above 0.7 and the factor analysis revealed that the items loaded properly on each dimension. Moreover, the gap scores of the SERVQUAL scale's dimensions pinpointed that the highest gap score was registered by the Tangibles dimension and the lowest gap score was registered by the Reliability dimension. CONCLUSIONS: Performing the ophthalmology service right the first time, contributes significantly to the improvement of the marketing effectiveness and the operating efficiency. PMID- 29796436 TI - Leber's hereditary optic neuropathy - Case report. AB - : Leber's hereditary optic neuropathy is the most common mitochondrial condition and is characterized by bilateral, painless, subacute visual loss that develops during young adult life. LHON is a rare condition and this lack of knowledge can make doctors suspect and treat for other causes of vision loss. Typically, a series of tests are performed to confirm LHON diagnosis or exclude any other conditions. We presented the case of two brothers, HB, of 40 years old and HF, of 38 years old, who presented with a decrease in visual acuity in both eyes. The patients had been diagnosed with optic atrophy of unknown cause a long time ago, but no further investigations were made. They were treated with corticosteroids, antioxidants and vasodilators, but with no significant benefit. A blood test of the mitochondrial DNA, a magnetic resonance imaging and an optic coherence tomography of the optic nerve and macula were part of the following assessment of our patients. The mitochondrial DNA analyses revealed the 3460 G>A mutation on the mtND1 gene in both patients. Based on the medical history, the fundus aspect, the optic coherence tomography and the paraclinical investigations of the diagnosis of Leber's hereditary optic neuropathy were established in both patients. We started the treatment with idebenone and we evaluated the patients after three months. ABBREVIATIONS: LHON = Leber's hereditary optic neuropathy, mtDNA = mitochondrial DNA, VA = visual acuity, CF = count fingers, OCT = optical coherence tomography, RNFL = retinal nerve fiber layer, GCL = ganglion cells layer, MS = multiple sclerosis, MRI = magnetic resonance imaging, MTI = magnetization transfer imaging, MTR = magnetization transfer ratio. PMID- 29796437 TI - Leukemic retinophaty, the first manifestation in a case of acute myelogenous leukemia. AB - A 42-year-old woman, without a specific medical history presented at the Department of Emergency Ophthalmology accusing marked decrease of vision for the left eye (VA 1/ 100). The eye examination revealed an optic neuropathy with multiple retinal hemorrhages at the level of both eyes, but more acutely on the left eye. The brain computer tomography (CT) excluded the suspicion of increasing intracranial pressure. The common blood tests such as complete blood count (CBC), erythrocyte sedimentation rate, and inflammatory markers raised a high suspicion of a malignant haematological disease. PMID- 29796438 TI - Multiple sclerosis with ophthalmologic onset - case report. AB - Ophthalmological and neurological signs and symptoms were assessed in a patient diagnosed with retrobulbar optic neuritis associated with multiple sclerosis (MS). The patient presented with progressive decrease of visual acuity, intermittent diplopia, paresthesia of the left arm and equilibrium disturbances. The complete ophthalmologic examination (clinical examination, visual field, optical coherence tomography) along with an MRI exam supported the diagnosis of MS with active lesions associated with retrobulbar optic neuritis. The corticosteroid therapy, followed by betaferon led to the remission of both ophthalmological and neurological signs. The multidisciplinary approach of the case played an important role in the early establishment of the diagnosis as well as the functional recovery of this patient. PMID- 29796439 TI - Various therapies for ocular surface diseases. AB - : This paper aims to discuss various therapeutical strategies (corneal cross linking, amniotic membrane transplantation with or without autologous serum application, medical regenerative therapy) for treating ocular surface diseases according to medical indications, etiology, local and general status of the patient. Besides the evolution and treatment of the lesions induced by corneal foreign body, ocular burns, neurotrophic keratitis, pterygium removal, Mooren's ulcer, this paper also follows and evaluates the migration, stratification and development of corneal epithelium. Of course, the success of the treatment depended on the therapeutic approach, the cause of the disease, the status of the eye and the patients' compliance. All cases presented had good results, proving once again, that a well-chosen therapeutic approach ensures the improvement or cure for many ocular surface diseases nowadays. ABBREVIATIONS: BVCA = best corrected visual acuity, OCT = optical coherence tomography, CLX = corneal cross linking. PMID- 29796440 TI - Developing Novel Machine Learning Algorithms to Improve Sedentary Assessment for Youth Health Enhancement. AB - Sedentary behavior of youth is an important determinant of health. However, better measures are needed to improve understanding of this relationship and the mechanisms at play, as well as to evaluate health promotion interventions. Wearable accelerometers are considered as the standard for assessing physical activity in research, but do not perform well for assessing posture (i.e., sitting vs. standing), a critical component of sedentary behavior. The machine learning algorithms that we propose for assessing sedentary behavior will allow us to re-examine existing accelerometer data to better understand the association between sedentary time and health in various populations. We collected two datasets, a laboratory-controlled dataset and a free-living dataset. We trained machine learning classifiers separately on each dataset and compared performance across datasets. The classifiers predict five postures: sit, stand, sit-stand, stand-sit, and stand?walk. We compared a manually constructed Hidden Markov model (HMM) with an automated HMM from existing software. The manually constructed HMM gave more F1-Macro score on both datasets. PMID- 29796441 TI - Differential effects of various soy isoflavone dietary supplements (nutraceuticals) on bacterial growth and human fibroblast viability. AB - Flavonoids, polyphenolic compounds present in many food products, affect growth of different bacterial species when tested as purified or synthetic substances. They can also influence gene expression in human cells, like fibroblasts. Here, we asked if soy isoflavone extracts, commonly used in many products sold as anti menopausal dietary supplements, influence bacterial growth similarly to a synthetic isoflavone, genistein. Four commercially available products were tested in amounts corresponding to genistein concentrations causing inhibition of growth of Vibrio harveyi (a model bacterium sensitive to this isoflavone) and Escherichia coli (a model bacterium resistant to genistein). Differential effects of various extracts on V. harveyi and E. coli growth, from stimulation, to no changes, to inhibition, were observed. Moreover, contrary to genistein, the tested extracts caused a decrease (to different extent) in viability of human dermal fibroblasts. These results indicate that effects of various soy isoflavone extracts on bacterial growth and viability of human cells are different, despite similar declared composition of the commercially available products. PMID- 29796442 TI - The favourable effect of catechin in electrochemotherapy in human pancreatic cancer cells. AB - Until recently, green tea polyphenols were considered strong antioxidants. However, the latest reports have revealed that bioflavonoids can play a multiple role in anticancer therapy, including the inhibition of cell proliferation and generation of the oxidative stress in a dose-dependent manner. The presented research was designed to examine the potential of the green tea (+/-)-catechin as a reinforcement of the electrochemotherapy (ECT) with cisplatin in pancreatic cancer in vitro. The study was performed on two cell lines of the pancreatic ductal adenocarcinoma (PDA) - parental EPP85-181P and multidrug-resistant EPP85 181RNOV. Prior to the ECT protocol the cells were preincubated with high or low concentration of catechin for 2 or 24 hours, respectively. We assessed the influence of preincubation on the cisplatin toxicity with and without electroporation (EP), the electrosensitivity of PDA cell lines and the uptake of the daunorubicin and propidium iodide. Additionally, we evaluated the antioxidative properties of catechin by the measurement of the ROS-related fluorescence and the immunoreactivity of the oxidative stress-related enzymes superoxide dismutase (SOD2) and glutathione S-transferase (GST). We found that co treatment with catechin can firmly enhance the efficacy of electroporation with cisplatin in vitro. More favorable effect was obtained for 2-hour incubation, which indicates the involvement of the transcriptional-independent mechanisms of catechin action. The effect may be partially explained by the increased oxidative stress level, which was higher in multidrug-resistant cells. However, further studies on cisplatin-catechin interplay and the thorough examination of the catechin-cell membrane interaction need to be performed. PMID- 29796444 TI - Discrimination analysis of excitatory and inhibitory neurons using Raman spectroscopy. AB - We have succeeded in discriminating between intact excitatory and inhibitory neuronal cells with Raman analysis. Excitatory and inhibitory neurons have several differences in their electric activities, but it can be difficult to determine their types based only on visual appearances. As Raman spectroscopy does not require any staining or labeling, its use in live neuronal cells is possible. In the present study, we used primary neurons obtained from rat cerebral cortexes, which we cultured on a glial feeder layered culturing dish for 15 days. The Raman spectra of the intact neurons on the dish were obtained; the neurons were then immunostained and their types determined. Partial least squares regression-discriminant analysis (PLSR-DA) was employed for classification of the excitatory and inhibitory neurons. The results demonstrated a high feasibility for use of Raman spectroscopy for discrimination analysis of inhibitory and excitatory neurons in a nondestructive manner. PMID- 29796443 TI - The interaction of new oxicam derivatives with lipid bilayers as measured by calorimetry and fluorescence spectroscopy. AB - The purpose of the present work was to assess the ability of five new oxicam analogues to interact with the lipid bilayers. To characterize the interaction of newly synthesized NSAIDs (non-steroidal anti-inflammatory drugs) analogues with DPPC lipid bilayers the two following techniques were applied - differential scanning calorimetry (DSC) and fluorescence spectroscopy. The results obtained by these experimental approaches show that new oxicams analogues interact with the lipid model membranes under consideration. As demonstrated both in calorimetric and spectroscopic studies, the greatest influence on the thermotropic properties of the lipid membrane and on the quenching of fluorescence of Laurdan and Prodan was exerted by a derivative named PR47 containing in its structure a two-carbon aliphatic linker with a carbonyl group, as well as bromine and trifluoromethyl substituents. PMID- 29796445 TI - In situ growth of graphdiyne on arbitrary substrates with a controlled-release method. AB - A versatile controlled-release method was developed for the in situ growth of graphdiyne on arbitrary substrates. Cu2+-Ions escaped from the polyvinylpyrrolidone/copper acetate film on the surface of various substrates (e.g. SiO2, ZnO, Al, etc.), acting as the catalyst for the acetylenic coupling reaction. PMID- 29796446 TI - Advancing semiconductor-electrocatalyst systems: application of surface transformation films and nanosphere lithography. AB - Photoelectrochemical (PEC) cells offer the possibility of carbon-neutral solar fuel production through artificial photosynthesis. The pursued design involves technologically advanced III-V semiconductor absorbers coupled via an interfacial film to an electrocatalyst layer. These systems have been prepared by in situ surface transformations in electrochemical environments. High activity nanostructured electrocatalysts are required for an efficiently operating cell, optimized in their optical and electrical properties. We demonstrate that shadow nanosphere lithography (SNL) is an auspicious tool to systematically create three dimensional electrocatalyst nanostructures on the semiconductor photoelectrode through controlling their morphology and optical properties. First results are demonstrated by means of the photoelectrochemical production of hydrogen on p type InP photocathodes where hitherto applied photoelectrodeposition and SNL deposited Rh electrocatalysts are compared based on their J-V and spectroscopic behavior. We show that smaller polystyrene particle masks achieve higher defect nanostructures of rhodium on the photoelectrode which leads to a higher catalytic activity and larger short circuit currents. Structural analyses including HRSEM and the analysis of the photoelectrode surface composition by using photoelectron spectroscopy support and complement the photoelectrochemical observations. The optical performance is further compared to theoretical models of the nanostructured photoelectrodes on light scattering and propagation. PMID- 29796449 TI - Low-cost, flexible, disinfectant-free and regular-array three-dimensional nanopyramid antibacterial films for clinical applications. AB - In this work, a low-cost, scalable and highly repeatable approach was developed to prepare polystyrene films with three-dimensional nanopyramids on the surface. The nanopyramids have a tunable aspect ratio and more importantly, their anti bacterial performance has been systematically studied. The effectiveness of the nanopyramids on E. coli growth inhibition and the role of the nanostructure aspect ratio were carefully studied through scanning electron microscopy and confocal laser scanning microscopy. The results showed an excellent antibacterial performance with more than 90% reduction in the E. coli population in all nanopyramid samples after a 168 h prolonged incubation time. The nanopyramid film developed here can be used for clinical and commercial applications to prevent the growth of pathogenic bacteria on various surfaces. PMID- 29796447 TI - Copper(ii)-benzotriazole coordination compounds in click chemistry: a diagnostic reactivity study. AB - This diagnostic study aims to shed light on the catalytic activity of a library of Cu(ii) based coordination compounds with benzotriazole-based ligands. We report herein the synthesis and characterization of five new coordination compounds formulated as [CuII(L4)(MeCN)2(CF3SO3)2] (1), [CuII(L5)2(CF3SO3)2] (2), [CuII(L6)2(MeCN)(CF3SO3)].(CF3SO3) (3), [CuII(L6)2(H2O)(CF3SO3)].(CF3SO3).2(Me2CO) (4), and [Cu(L1)2(L1')2(CF3SO3)2]2.4(CF3SO3).8(Me2CO) (5), derived from similar nitrogen based ligands. The homogeneous catalytic activity of these compounds along with our previously reported coordination compounds (6-13), derived from similar ligands, is tested against the well-known Cu(i)-catalysed azide-alkyne cycloaddition reaction. The optimal catalyst [CuII(L1)2(CF3SO3)2] (10) activates the reaction to afford 1,4-disubstituted 1,2,3-triazoles with yields up to 98% and without requiring a reducing agent. Various control experiments are performed to optimize the method and examine parameters such as ligand variation, metal coordination geometry and environment, in order to elucidate the behaviour of the catalytic system. PMID- 29796450 TI - Direct measurements of the temperature, depth and processing dependence of phenyl ring dynamics in polystyrene thin films by beta-detected NMR. AB - There is indirect evidence that the dynamics of a polymer near a free surface are enhanced compared with the bulk but there are few studies of how dynamics varies with depth. beta-Detected nuclear spin relaxation of implanted 8Li+ has been used to directly probe the temperature and depth dependence of the gamma-relaxation mode, which is due to phenyl rings undergoing restricted rotation, in thin films of atactic deuterated polystyrene (PS-d8) and determine how the depth dependence of dynamics is affected by sample processing, such as annealing, floating on water and the inclusion of a surfactant, and by the presence of a buried interface. The activation energy for the gamma-relaxation process is lower near the free surface. Annealing the PS-d8 films and then immersing in water to mimic the floating procedure used to transfer films had negligible effects on the thickness of the region near the free surface with enhanced mobility. Measurements on a bilayer film indicate enhanced phenyl ring dynamics near the buried interface compared with a single film at the same depth. PS-d8 films annealed with the surfactant sodium dodecyl sulfate (SDS) deposited on the surface show enhanced dynamics in the bulk compared with a pure PS-d8 film and a PS-d8 film where the SDS was washed away. There is less contrast between the surface and bulk in the SDS-treated sample, which could account for the elimination of the Tg confinement effect observed in films containing SDS [Chen and Torkelson, Polymer, 2016, 87, 226]. PMID- 29796451 TI - Field-induced dipolar attraction between like-charged colloids. AB - The field induced anisotropic interactions between like-charged colloidal particles is studied using direct numerical simulations, where the polarization of the electric double layer is explicitly computed under external AC electric fields. These interactions are found to depend on the magnitude E0 and frequency omega of the applied field, as well as the zeta potential, the Debye length, and the relative orientation of the particles. We also determined the range of E0 and omega over which a dipolar attraction is induced between a pair of like-charged colloids. Finally, we performed simulations for systems of six and twelve colloidal particles to study the stability of pear-chain-like configurations. PMID- 29796454 TI - Construction of half-sandwich multinuclear complexes including tunnel architectures via C-H-activation-directed assembly. AB - Three aromatic ligands containing carboxyl- or nitrogen-substituted groups were employed in the construction of half-sandwich complexes via C-H activation directed assembly, leading to the construction of eleven multinuclear organometallic iridium or rhodium complexes, including those of bi-, tetra-, hexa and octanuclear, under mild conditions, with the help of N-donor linkers. These complexes were characterized by proton NMR, IR spectroscopy, elemental analysis, electrospray ionization (ESI) mass spectrometry and single-crystal X-ray diffraction analysis. In these complexes, two complexes were observed to exist as isomers, and several racemic enantiomers can be found. X-ray crystal structure determinations show that a series of supramolecular tunnel architectures are formed by stacking through hydrogen-bond interactions, and solvent or trifluoromethylsulfonate anion guests were found to be located in certain parts of the channels. This work represents the first successful construction of octanuclear half-sandwich complexes based on the cleavage of C-H bonds. PMID- 29796452 TI - Modelling of surfactant-driven front instabilities in spreading bacterial colonies. AB - The spreading of bacterial colonies at solid-air interfaces is determined by the physico-chemical properties of the involved interfaces. The production of surfactant molecules by bacteria is a widespread strategy that allows the colony to efficiently expand over the substrate. On the one hand, surfactant molecules lower the surface tension of the colony, effectively increasing the wettability of the substrate, which facilitates spreading. On the other hand, gradients in the surface concentration of surfactant molecules result in Marangoni flows that drive spreading. These flows may cause an instability of the circular colony shape and the subsequent formation of fingers. In this work, we study the effect of bacterial surfactant production and substrate wettability on colony growth and shape within the framework of a hydrodynamic thin film model. We show that variations in the wettability and surfactant production are sufficient to reproduce four different types of colony growth, which have been described in the literature, namely, arrested and continuous spreading of circular colonies, slightly modulated front lines and the formation of pronounced fingers. PMID- 29796455 TI - Dissociative adsorption of a multifunctional compound on a semiconductor surface: a theoretical study of the adsorption of hydroxylamine on Ge(100). AB - The adsorption behavior of hydroxylamine on a Ge(100) surface was investigated using density functional theory (DFT) calculations. These calculations predicted that hydroxylamine, a multifunctional compound consisting of a hydroxyl group and an amine group, would initially become adsorbed through N-dative bonding, or alternatively through the hydroxyl group via O-H dissociative adsorption. An N-O dissociative reaction may also occur, mainly via N-dative molecular adsorption, and the N-O dissociative product was calculated to be the most stable of all the possible adsorption structures. The calculations furthermore indicated the formation of the N-O dissociative product from the N-dative structure to be nearly barrierless and the dissociated hydroxyl and amine groups to be bonded to two Ge atoms of adjacent Ge dimers. Simulated STM images suggested the change in electron density that would occur upon adsorption of hydroxylamine in various adsorption configurations, and specifically indicated the N-O dissociative product to have greater electron density around the amine groups, and the hydroxyl groups to mainly contribute electron density to the unoccupied electronic states. PMID- 29796456 TI - The mechanism of photocatalytic CO2 reduction by graphene-supported Cu2O probed by sacrificial electron donors. AB - Cu2O nanoparticles of 5 nm average size have been adsorbed (1.74 wt% loading) on defective graphene (Cu2O/G) previously obtained by the pyrolysis of alginic acid sodium salt. The Cu2O crystal phase was determined by XRD. XPS shows that the external layers of the Cu2O nanoparticles are constituted mainly of Cu+ although a certain percentage of CuII+ was also present. Cu2O/G is a photocatalyst for the CO2 reduction to methane in the presence of sacrificial agents, and the rate of CH4 production depends on the oxidation potential of the electron donor. This relationship supports a mechanism involving photoinduced charge separation with the generation of electrons and holes. The highest CH4 formation rate upon UV-Vis irradiation of Cu2O/G with a 300 W Xe lamp was achieved for dimethylaniline reaching 326 MUmol CH4 per g per h. The spectral response of the Cu2O photocatalyst shows, however, that the response of the photocatalyst is mainly due to UV irradiation, indicating that light absorption at the low Cu2O loading on the Cu2O/G photocatalyst occurs mainly on the graphene component. PMID- 29796458 TI - Aromatic cage-like B34 and B35+: new axially chiral members of the borospherene family. AB - Shortly after the discovery of all-boron fullerenes D2d B40-/0 (borospherenes), the first axially chiral borospherenes C3/C2 B39- were characterized in experiments in 2015. Based on extensive global minimum searches and first principles theory calculations, we present herein two new axially chiral members to the borospherene family: the aromatic cage-like C2 B34(1) and C2 B35+(2). Both B34(1) and B35+(2) feature one B21 boron triple chain on the waist and two equivalent heptagons and hexagons on the cage surface, with the latter being obtained by the addition of B+ into the former at the tetracoordinate defect site. Detailed bonding analyses show that they follow the universal bonding pattern of sigma + pi double delocalization, with 11 delocalized pi bonds over a sigma skeleton. Extensive molecular dynamics simulations show that these borospherenes are kinetically stable below 1000 K and start to fluctuate at 1200 K and 1100 K, respectively. The IR, Raman, and UV-vis spectra of 1 and 2 are computationally simulated to facilitate their experimental characterization. PMID- 29796459 TI - A revisit to the structure of Au20(SCH2CH2Ph)16: a cubic nanocrystal-like gold kernel. AB - Coinage metal clusters stabilized by organic ligands such as phosphine or organothiolate are well known to possess multi-twinned gold cores, and the face centered-cubic (fcc) metal atom packing is unstable until the cluster size reaches a certain threshold. In this study, we searched for the smallest size gold nanocrystal protected by thiolate ligands by means of the crystal facet cleavage (CFC) method. Starting from the nanocrystal-like Au28(SR)20 cluster, after cleaving two different crystal facets and patching the ligand shells, we obtained five nanocrystal-like Au20(SR)16 isomers. These fcc-structured Au20 clusters were quite different from non-fcc Au20(SPh-tBu)16; the latter's total structure was determined by single X-ray diffraction. By employing dispersion correction density functional theory (DFT-D) calculations and considering ligand effects, we found that fcc-structured Au20(SR)16 isomers had comparable or even lower energies when compared with the non-fcc structure found in Au20(SPh-tBu)16. Furthermore, the calculation of optical absorption spectra based on predicted fcc isomers indicated that the cubic nanocrystal-like isomer structure is a good candidate to understand the structure of the Au20(SCH2CH2Ph)16 cluster. PMID- 29796460 TI - A facile and processable integration strategy towards Schiff-base polymer-derived carbonaceous materials with high lithium storage performance. AB - Herein, a novel in situ concentrated-solution-induced polymerization strategy is developed towards the integration of Schiff-base networks into graphene foam with processable and moldable characteristics. This bottom-up design process endows the resultant composites with a high nitrogen content (9.6 at%) and abundant porosity and accordingly demonstrates high lithium storage properties. PMID- 29796461 TI - Standing, lying, and sitting: translating building principles of the cell membrane to synthetic 2D material interfaces. AB - A striking number of problems in modern materials chemistry relate to controlling structure at scales 5-10 nm, important in applications ranging from nanoscale electronics to organic materials for energy conversion. Interfacial patterning is potentially valuable in establishing and stabilizing high-resolution structural features. While chemical patterning at such short length scales is unusually difficult using many traditional top-down approaches, it has been achieved with remarkable efficiency and chemical diversity in two seemingly unrelated areas: in the lipid bilayers that make up cell membranes, and in the noncovalent functionalization of 2D materials such as graphene. At the intersection of these two areas are lessons of significant utility for controlling synthetic material interface chemistry across a range of length scales. PMID- 29796462 TI - Metal- and base-free synthesis of imidazo[1,2-a]pyridines through elemental sulfur-initiated oxidative annulation of 2-aminopyridines and aldehydes. AB - The elemental sulfur-promoted oxidative cyclization reaction for the efficient synthesis of substituted imidazo[1,2-a]pyridines has been developed. Easily available 2-aminopyridines and aldehydes were directly assembled in a highly atom economical fashion through oxidative annulation under metal- and base-free conditions. Besides arylacetaldehydes, aliphatic aldehydes were also compatible with this system to deliver the alkyl-substituted imidazo[1,2-a]pyridines in excellent yields with the capability of gram-scale synthesis. PMID- 29796463 TI - Damage in elastomers: healing of internally nucleated cavities and micro-cracks. AB - Following on the work of Poulain et al. (Damage in elastomers: Nucleation and growth of cavities, micro-cracks, and macro-cracks, Int. J. Fract., 2017, 205, 1 21), this paper presents an investigation of the response of cavities/cracks internally nucleated within a transparent PDMS elastomer that is confined between two firmly embedded stiff beads and subjected to quasistatic cyclic loading unloading. Specifically, it is observed that cracks that nucleate and propagate to reach tens of microns in length during the loading can heal completely upon unloading. They do so autonomously within a time scale of seconds. Furthermore, the regions of the elastomer that experience healing appear to acquire higher strength or toughness. PMID- 29796465 TI - Photo-induced heat generation in non-plasmonic nanoantennas. AB - Light-to-heat conversion in non-plasmonic, high refractive index nanoantennas is a key topic for many applications, including Raman sensing, laser writing, nanofabrication and photo-thermal therapy. However, heat generation and propagation in non-plasmonic antennas is increasingly debated and contradictory results have been reported so far. Here we report a finite element analysis of the steady-state temperature distribution and heat flow in SiO2/Si core/shell systems (silicon nanoshells) irradiated with different continuous wave lasers (lambda = 532, 633 and 785 nm), under real working conditions. The complex interplay among the optical properties, morphology, degree of crystallinity of the nanoshells, thickness dependence of thermal conductivity and interactions with the substrate has been elucidated. This study reveals that all of these parameters can be appropriately combined for obtaining either stable nanoshells for Raman sensing or highly efficient sources of local heating. The optimal balance between thermal stability and field enhancement was found for crystalline Si shell layers with thicknesses ranging from 40 to 60 nm, irradiated by a NIR laser source. On the other hand, non-conformal amorphous or crystalline shell layers with a thickness >50 nm can reach a very high local temperature (above 1000 K) when irradiated with a low power density (less than 1 mW MUm-2) laser sources. This work provides a general approach for an extensive investigation of the opto-thermal properties of high-index nanoantennas. PMID- 29796467 TI - Concentration-dependent swelling and structure of ionic microgels: simulation and theory of a coarse-grained model. AB - We study swelling and structural properties of ionic microgel suspensions within a comprehensive coarse-grained model that combines the polymeric and colloidal natures of microgels as permeable, compressible, charged spheres governed by effective interparticle interactions. The model synthesizes the Flory-Rehner theory of cross-linked polymer gels, the Hertz continuum theory of effective elastic interactions, and a theory of density-dependent effective electrostatic interactions. Implementing the model using Monte Carlo simulation and thermodynamic perturbation theory, we compute equilibrium particle size distributions, swelling ratios, volume fractions, net valences, radial distribution functions, and static structure factors as functions of concentration. Trial Monte Carlo moves comprising particle displacements and size variations are accepted or rejected based on the total change in elastic and electrostatic energies. The theory combines first-order thermodynamic perturbation and variational free energy approximations. For illustrative system parameters, theory and simulation agree closely at concentrations ranging from dilute to beyond particle overlap. With increasing concentration, as microgels deswell, we predict a decrease in the net valence and an unusual saturation of pair correlations. Comparison with experimental data for deionized, aqueous suspensions of PNIPAM particles demonstrates the capacity of the coarse-grained model to predict and interpret measured swelling behavior. PMID- 29796466 TI - Paramagnetic nanoemulsions with unified signals for sensitive 19F MRI cell tracking. AB - As a promising cell tracking technology, 19F MRI suffers from low sensitivity. Here, fluorinated nanoemulsions with a unified 19F signal and paramagnetic relaxation enhancement were developed as 19F MRI cellular tracers with high stability, size controllability, biocompatibility, cellular uptake, and dual modality for sensitive in vivo RAW264.7 cell tracking. PMID- 29796468 TI - Synthesis of a superparamagnetic ultrathin FeCO3 nanorods-enzyme bionanohybrid as a novel heterogeneous catalyst. AB - Herein we report a straightforward synthesis of an ultrathin protein-iron(ii) carbonate nanorods (FeCO3-NRs) heterogeneous bionanohybrid at room temperature and in aqueous media. The enzyme induced the in situ formation of well-dispersed FeCO3 NRs on a protein network. The addition of NaBH4 as a reducing agent allowed us to obtain nanorods (5 * 40 nm) with superparamagnetic properties. This bionanohybrid showed excellent catalytic results in reduction, oxidation and C-C bond reactions. PMID- 29796469 TI - Polymer nanoparticle sizes from dynamic light scattering and size exclusion chromatography: the case study of polysilanes. AB - Dynamic light scattering (DLS) and size exclusion chromatography (SEC) are among the most popular methods for determining polymer sizes in solution. Taking dendritic and network polysilanes as a group of least soluble polymer substances, we critically compare and discuss the difference between nanoparticle sizes, obtained by DLS and SEC. Polymer nanoparticles are typically in poor solution conditions below the theta point and are therefore in the globular conformation. The determination of particle sizes in the presence of attractive interactions is not a trivial task. The only possibility to measure, aggregation-free, the true molecular size of polymer nanoparticles in such a solution regime, is to perform the experiment with a dilute solution of globules (below the theta point and above the miscibility line). Based on the results of our polysilane measurements, we come to a conclusion that DLS provides more reliable results than SEC for dilute solutions of globules. General implications for the size measurements of polymer nanoparticles in solution are discussed. PMID- 29796470 TI - Charge-induced structural transition between seashell-like B29- and B29+ in 18 pi electron configurations. AB - Recent joint experimental and theoretical investigations have shown that seashell like C2 B28 is the smallest neutral borospherene reported to date, while seashell like Cs B29- (1-) as a minor isomer competes with its quasi-planar counterparts in B29- cluster beams. Extensive global minimum searches and first-principles theory calculations performed in this work indicate that with two valence electrons detached from B29-, the B29+ monocation favors a seashell-like Cs B29+ (1+) much different from Cs B29- (1-) in geometry which is overwhelmingly the global minimum of the system with three B7 heptagonal holes in the front, on the back, and at the bottom, respectively, unveiling an interesting charge-induced structural transition from Cs B29- (1-) to Cs B29+ (1+). Detailed bonding analyses show that with one less sigma bond than B29- (1-), Cs B29+ (1+) also possesses nine delocalized pi-bonds over its sigma-skeleton on the cage surface with a sigma + pi double delocalization bonding pattern and follows the 2(n + 1)2 electron counting rule for 3D spherical aromaticity (n = 2). B29+ (1+) is therefore the smallest borospherene monocation reported to date which is pi isovalent with the smallest neutral borospherene C2 B28. The IR, Raman, and UV vis spectra of B29+ (1+) are computationally simulated to facilitate its spectroscopic characterization. PMID- 29796471 TI - Correction: Ameliorative role of camel whey protein and rosuvastatin on induced dyslipidemia in mice. AB - Correction for 'Ameliorative role of camel whey protein and rosuvastatin on induced dyslipidemia in mice' by Nashwa Ahmed El-Shinnawy et al., Food Funct., 2018, 9, 1038-1047. PMID- 29796472 TI - Chromo-luminescent selective detection of fluoride ions by a copper(ii) bis(terpyridine) complex solution via a displacement approach. AB - Herein, for the first time, we have reported a copper(ii) bis(terpyridine) complex solution for instant 'naked eye' chromo-luminescent selective detection of fluoride ions in an acetonitrile medium at micromolar concentration. The copper complex [Cu(ii) (L)2] (NO3)2 [where L = 4'-(4-N,N'-dimethylaminophenyl) 2,2':6',2''-terpyridine] was characterized by mass spectroscopy and the terpyridine ligand by 1H NMR spectroscopy. The complex solution selectively discriminates F- ions from other anions such as AcO-, Br-, Cl-, CN-, H2PO4-, HSO4 , and I- in acetonitrile media via exceptional optical changes. The optical changes were evaluated by UV-visible and fluorescence techniques. Studies on the binding characteristics of the copper complex solution with fluoride ions revealed a displacement of copper ions from the complex solution as CuF2 resulting in the significant optical changes. Furthermore, displacement of Cu(ii) from the complex was established by means of mass spectroscopy in the presence of 20 equivalents of fluoride ions. The limit of detection (LOD) was found to be 5.07 MUM which is within the permissible range of fluoride ions in drinking water set by the World Health Organization (WHO). PMID- 29796477 TI - A novel three-fluorophore system as a ratiometric sensor for multiple protease detection. AB - A synthetic three-fluorophore system with two enzymatically cleavable linkers has been developed for the simultaneous detection of two proteases in a mixture. The probe was designed to afford single excitation/triple emission ratiometric detection through a fluorescence change during the cleavage of a peptide linker. The developed assays were verified for trypsin and chymotrypsin as the model enzymes. PMID- 29796478 TI - Diffusiophoretic exclusion of colloidal particles for continuous water purification. AB - It has been observed that colloidal particles are anomalously repelled from the interface of nanoporous materials and water by up to hundreds of micrometers even if there is no additional external field present. Recently, the physical origin of this anomalous repulsion has turned out to be diffusiophoretic migration triggered by an ion exchange process through the interface. Since the repulsive force is induced by a salt gradient only, the phenomenon can be applied to a microscale water purification platform without the need for any external power sources. In this work, we suggest a micro/nanofluidic device for continuous water purification utilizing long-range diffusiophoretic migration around ion exchangeable surfaces. An ion concentration boundary layer was characterized by the Sherwood number (Sh) which is a key dimensionless number to describe the purification process. Depending on Sh, we have theoretically and experimentally demonstrated that long-range diffusiophoretic exclusion can be used for continuous water purification. Finally, our platform can be used as a highly energy-efficient and portable water treatment option for operations such as purification, disinfection, water softening, etc. PMID- 29796479 TI - Anisotropic chemical strain in cubic ceria due to oxygen-vacancy-induced elastic dipoles. AB - Accurate characterization of chemical strain is required to study a broad range of chemical-mechanical coupling phenomena. One of the most studied mechano chemically active oxides, nonstoichiometric ceria (CeO2-delta), has only been described by a scalar chemical strain assuming isotropic deformation. However, combined density functional theory (DFT) calculations and elastic dipole tensor theory reveal that both the short-range bond distortions surrounding an oxygen vacancy and the long-range chemical strain are anisotropic in cubic CeO2-delta. The origin of this anisotropy is the charge disproportionation between the four cerium atoms around each oxygen-vacancy (two become Ce3+ and two become Ce4+) when a neutral oxygen-vacancy is formed. Around the oxygen-vacancy, six of the Ce3+-O bonds elongate, one of the Ce3+-O bond shorten, and all seven of the Ce4+ O bonds shorten. Further, the average and maximum chemical strain values obtained through tensor analysis successfully bound the various experimental data. Lastly, the anisotropic, oxygen-vacancy-elastic-dipole induced chemical strain is polarizable, which provides a physical model for the giant electrostriction recently discovered in doped and non-doped CeO2-delta. Together, this work highlights the need to consider anisotropic tensors when calculating the chemical strain induced by dilute point defects in all materials, regardless of their symmetry. PMID- 29796485 TI - Development of functional black phosphorus nanosheets with remarkable catalytic and antibacterial performance. AB - Highly dispersed 2D-nanostructured ultrathin black phosphorus nanosheets (BPNs) integrated Au nanoparticles (AuNPs) hybrids were constructed in situ through a facile and environmentally friendly strategy. No additional reductants, surfactants, or polymer templates were introduced during this green and convenient synthesis process. The resulting AuNPs/BPNs nanohybrids were characterized by UV-vis, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The content of BPNs plays an essential role in modulating the morphologies and chemical states of AuNPs/BPNs hybrids, which have been investigated systematically and are discussed in detail. As high density ultrasmall AuNPs are properly stabilized and accommodated without passivation by the surrounding ultrathin BPNs, the resulting AuNPs/BPNs hybrids exhibit excellent catalytic/antibacterial properties and long-term stabilities, benefiting from a possible synergistic enhancement effect between AuNPs and BPNs constructs. This simple, mild and environmentally benign strategy could be generalized to the preparation of other metal- or metal oxide-doped complexes and holds great promise for potential catalytic, bioanalytical and biomedical applications. PMID- 29796486 TI - A DFT assessment of some physical properties of iodine-centered halogen bonding and other non-covalent interactions in some experimentally reported crystal geometries. AB - A set of six binary complexes that feature iodine-centered halogen bonding, extracted from structures deposited in the Cambridge Structure Database, has been examined computationally using density functional theory calculations with the M06-2X global hybrid, and dispersion corrected B3LYP-D3 and B97-D3, to determine their equilibrium geometries, binding energies and electronic properties. The results show that gas phase calculations are very informative in evaluating what occurs in the solid state, even though these calculations ignore the importance of lattice packing and counter ion effects. The calculated binding energies for the non-covalent interactions responsible for these complexes lie between -4.15 and -7.48 kcal mol-1 (M06-2X), which enables us to characterize them as weak-to moderate in strength. The basis set superposition error energies are calculated to vary between 0.60 and 2.42 kcal mol-1 for all the complexes examined, even though an all-electron QZP basis set used in the analysis was of quadrupole-zeta (plus polarization) quality. Dispersion is found to have a profound effect on the binding energy of some of these complexes, and was estimated to be as large as 5.0 kcal mol-1. For one complex, the crystal geometry could not be precisely reproduced using a gas phase calculation. While both halogen- and hydrogen bonding interactions were found competitive, they cooperate with each other to determine the stable configuration of the binary complex. The molecular electrostatic surface potential, quantum theory of atoms in molecules, and reduced density gradient non-covalent Interaction models were utilized to arrive at a fundamental understanding of the various inter- and intra-molecular molecular interactions involved, as well as some other previously-overlooked non covalent interactions that emerge in the modelling. PMID- 29796487 TI - Photoelectrochemical hydrogen generation employing a Cu2O-based photocathode with improved stability and activity by using NixPy as the cocatalyst. AB - With the tactical integration of band edge energetics concepts in semiconducting films to reduce charge recombination and photocorrosion, an improvement in the photocurrent can be achieved by introducing CuO and NixPy into Cu2O films. Photodegradation limitations of Cu2O are overcome by the Cu2O-CuO-NixPy photocathode. NixPy, because of its excellent electrocatalytic hydrogen evolution activity, helps in obtaining better stability and activity. The individual effects of CuO and NixPy have been investigated and it is found that the activity enhancement stems mainly from the contribution of NixPy, whereas CuO helps with the unidirectional flow of photogenerated charges to prevent the photocorrosion of Cu2O. Relative to bare and modified Cu2O, Cu2O-CuO-NixPy shows a considerable reduction in the overpotential and a remarkable improvement in the photocurrent at 0 V (vs. RHE). This is the first report on the use of NixPy as the co-catalyst in a Cu2O based photocathode system to improve its photostability as well as its activity. PMID- 29796494 TI - Synthesis and structural characterization of the first neptunium based metal organic frameworks incorporating {Np6O8} hexanuclear clusters. AB - Successful synthesis of the first transuranium metal-organic frameworks (TRU MOFs) involving tetravalent Np4+ is reported. These compounds were obtained from the controlled hydrolysis of Np4+ in the presence of dicarboxylate ligands. The final structures contain the [Np6O4(OH)4(H2O)6]12+ unit, which were never crystallized before with tetravalent neptunium, associated with ditopic ligands. PMID- 29796495 TI - beta-Diketone derivatives: influence of the chelating group on the photophysical and mechanofluorochromic properties. AB - A diphenyl-boron beta-diketonate complex was synthesized. Its photophysical properties were studied in solution and in the solid-state, and compared to those of its parent diketone and the corresponding difluoro-boron complex. TD-DFT calculations show that the molecular orbitals involved in the first Franck-Condon transition are very different for the three compounds studied. The difluoro-boron complex is strongly fluorescent in solution, and remains fluorescent in the solid state. The free diketone turns to be very weakly fluorescent in solution and displays significant Aggregation Induced Enhanced Emission (AIEE) in the crystalline state, which can be explained by a rigidification of the molecule, while the diphenyl-boron complex is weakly fluorescent in solution as well as in the solid-state. For the free diketone and the difluoro-boron complex a mechanofluorochromic response is observed upon grinding the crystalline powder in a mortar, while for the diphenyl-boron complex no fluorescence emission change is detected under these conditions. Overall, this study shows that the nature of the chelating group has a crucial influence on the photophysical and mechanofluorochromic properties of beta-diketonate complexes, leading to a wide variety of behaviors within the closely related structures of such derivatives. PMID- 29796496 TI - A connection between living liquid crystals and electrokinetic phenomena in nematic fluids. AB - We develop a formal analogy between configurational stresses in physically distinct systems, and study the flows that they induce when the configurations of interest include topological defects. Our primary focus is on electrokinetic flows in a nematic fluid under an applied electrostatic field, which we compare with a class of systems in which internal stresses are generated due to configurational changes (e.g., active matter, liquid crystal elastomers). The mapping allows the extension, within certain limits, of existing results on transport in electrokinetic systems to active transport. We study motion induced by a pair of point defects in a dipole configuration, and steady rotating flows due to a swirling vortex nematic director pattern. The connection presented allows the design of electrokinetic experiments that correspond to particular active matter configurations that may be easier to conduct and control in the laboratory. PMID- 29796497 TI - Ligand-promoted ruthenium-catalyzed meta C-H chlorination of arenes using N chloro-2,10-camphorsultam. AB - A practical meta C-H chlorination protocol is established via a Ru(0)-catalyzed ortho-metalation strategy. The use of N-chloro-2,10-camphorsultam as a new chlorinating agent is crucial for the success of the current reaction and an N heterocyclic carbene (NHC) ligand could significantly enhance the reactivity of the catalytic transformation. The mechanistic studies reveal that an unusual ortho C-H ruthenation relay process with ortho chlorination of the C-Ru bond is probably involved. PMID- 29796499 TI - Open-cell voltage and electrical conductivity of a protonic ceramic electrolyte under two chemical potential gradients. AB - BaZr0.8Y0.2O3-delta, which is a proton-conducting oxide used as an electrolyte for protonic ceramic fuel cells (PCFCs), possesses two mobile ionic charge carriers-oxygen ions and protons-in a crystalline lattice below 500 degrees C. The equilibrium concentrations of these charge carriers are dependent on water activity. This feature induces a complexity in the distribution of charge carriers within the electrolyte under the influence of the two chemical potential gradients of oxygen and water, which is a typical operating condition in PCFCs. This makes the theoretical derivations of the open-cell voltage and the electrical resistance of the electrolyte difficult. Here, we calculate the distributions of oxygen vacancies and protons across the electrolyte by solving diffusion equations based on the defect chemistry of BaZr0.8Y0.2O3-delta at 500 degrees C. We then extract the theoretical open-cell voltage and electrical conductivity of the electrolyte in a range of water and oxygen activities that is of interest for PCFCs. PMID- 29796498 TI - Label-free and high-throughput bioluminescence detection of uracil-DNA glycosylase in cancer cells through tricyclic cascade signal amplification. AB - We develop a label-free and high-throughput bioluminescence method for the sensitive detection of uracil DNA glycosylase (UDG) through enzyme-mediated tricyclic cascade signal amplification. This method exhibits high sensitivity with a detection limit as low as 0.00031 U mL-1, and it can be further applied for the measurement of enzyme kinetic parameters and the screening of UDG inhibitors as well as cancer cell analysis. PMID- 29796502 TI - Amorphous phase state diagrams and viscosity of ternary aqueous organic/organic and inorganic/organic mixtures. AB - A Dimer Coagulation, Isolation and Coalescence (DCIC) technique is used to probe the phase behaviour and glass transition temperatures of ternary aerosol mixtures. The DCIC technique is used to perform temperature and relative humidity dependent viscosity measurements at viscosities near 5 * 106 Pa s. Measurements include organic-organic and organic-inorganic mixtures composed of sucrose-citric acid and sucrose-sodium nitrate. The data reported here add additional insight into the wide discrepancies in glass transition temperatures reported for pure sodium nitrate. The phase diagram model used in the work of Rothfuss and Petters (Phys. Chem. Chem. Phys., 2017, 19, 6532-6545) is expanded to include multiple solute components. Data and model predictions of the mixtures are in good agreement with the modified model. These measurements are compared with values from Holographic Optical Tweezer (HOT) measurements taken at room temperature. Overall, the viscosities determined from the DCIC and HOT techniques are in good agreement. PMID- 29796500 TI - Manganese-52: applications in cell radiolabelling and liposomal nanomedicine PET imaging using oxine (8-hydroxyquinoline) as an ionophore. AB - The ionophore 8-hydroxyquinoline (oxine) has been used to radiolabel cells and liposomal medicines with 111In and, more recently, 89Zr, for medical nuclear imaging applications. Oxine has also shown promising ionophore activity for the positron-emitting radionuclide 52Mn that should allow imaging of labelled cells and nanomedicines for long periods of time (>14 days). However, to date, the radiometal complex formed and its full labelling capabilities have not been fully characterised. Here, we provide supporting evidence of the formation of [52Mn]Mn(oxinate)2 as the metastable complex responsible for its ionophore activity. The cell labelling properties of [52Mn]Mn(oxinate)2 were investigated with various cell lines. The liposomal nanomedicine, DOXIL(r) (Caelyx) was also labelled with [52Mn]Mn(oxinate)2 and imaged in vivo using PET imaging. [52Mn]Mn(oxinate)2 was able to label various cell lines with moderate efficiency (15-53%), however low cellular retention of 52Mn (21-25% after 24 h) was observed which was shown not to be due to cell death. PET imaging of [52Mn]Mn-DOXIL at 1 h and 24 h post-injection showed the expected pharmacokinetics and biodistribution of this stealth liposome, but at 72 h post-injection showed a profile matching that of free 52Mn, consistent with drug release. We conclude that oxine is an effective ionophore for 52Mn, but high cellular efflux of the isotope limits its use for prolonged cell tracking. [52Mn]Mn(oxinate)2 is effective for labelling and tracking DOXIL in vivo. The release of free radionuclide after liposome extravasation could provide a non-invasive method to monitor drug release in vivo. PMID- 29796503 TI - Aggregated initiators: defining their role in the ROP of rac-lactide. AB - Reported examples of aggregated initiators for the ring-opening polymerisation (ROP) of lactide often lack detailed investigations as to the nature of the active species, making it difficult to reconcile ligand design with performance. Here, we offer additional stability to the polynuclear titanium complexes, TiL(OiPr) (L = 9-14), through a bridging carboxylate anchored to the supporting amine bis(phenolate) ligands. An in-depth study of solution-state behaviour determined the process of assembly was driven by interactions between the carboxylate and a vacant site on a neighbouring titanium centre. Furthermore, we establish that mononuclear units form dynamic mixtures of polynuclear aggregates, with a clear relationship between nuclearity of the aggregates and the steric bulk on the ligand. Smaller aggregates displayed increased activity towards the ROP of rac-lactide. Furthermore, addition of a chiral centre, on the ligand framework, was investigated as a route to influence the selectivity of the polymerisation via easily-accessible initiators. PMID- 29796504 TI - Characterization of nano-porosity in molecular layer deposited films. AB - Molecular layer deposition (MLD) delivers (ultra-) thin organic and hybrid materials, with atomic-level thickness control. However, such layers are often reported to be unstable under ambient conditions, due to the interaction of water and oxygen with the hybrid structure, consequently limiting their applications. In this contribution, we investigate the impact of porosity in MLD layers on their degradation. Alucone layers were deposited by means of trimethylaluminium and ethylene glycol, adopting both temporal and spatial MLD and characterized by means of FT-IR spectroscopy, spectroscopic ellipsometry, and ellipsometric porosimetry. The highest growth per cycle (GPC) achieved by spatial MLD resulted in alucone layers with very low stability in ambient air, leading to their conversion to AlOx. Alucones deposited by means of temporal MLD, instead, showed a lower GPC and a higher ambient stability. Ellipsometric porosimetry showed the presence of open nano-porosity in pristine alucone layers. Pores with a diameter in the range of 0.42-2 nm were probed, with a relative content between 1.5% and 5%, respectively, which are attributed to the temporal and spatial MLD layers. We concluded that a correlation exists between the process GPC, the open-porosity relative content, and the degradation of alucone layers. PMID- 29796505 TI - A family of lanthanide compounds with reduced nitronyl nitroxide diradical: syntheses, structures and magnetic properties. AB - A novel nitronyl nitroxide diradical based on the pyrazine ring, BNITPz (1, BNITPz = 2,2'-(3,6-dimethylpyrazine-2,5-diyl)bis(1-hydroxy-4,4,5,5-tetramethyl 4,5-dihydro-1H-imidazole-1-oxyl-3-oxide)) and six new dinuclear compounds based on the reduced form of 1, namely [Ln(hfac)3]2(BHIMPz)(H2O)2 (Ln = Gd (2Gd), Dy (3Dy), Ho (4Ho), Er (5Er), Tm (6Tm), Yb (7Yb); BHIMPz = 2,2'-(3,6 dimethylpyrazine-2,5-diyl)bis(4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3 oxide); hfac = hexafluoroacetylacetonate) were prepared and characterized. Single crystal X-ray crystallographic analyses confirmed the diradical structure of 1, and revealed that complexes 2Gd-7Yb are isostructural and crystallize in the triclinic space group P1[combining macron]. The reduced form BHIMPz was confirmed by its longer N-O bond lengths and the characteristic N-H stretching absorption at 3500-3300 cm-1 of the IR spectroscopy of 2Gd-7Yb. In 2Gd-7Yb, the lanthanide ions are eight-coordinated in a square antiprism environment (D4d). Two symmetric related Ln(iii) ions are bridged by the reduced BHIMPz ligand to form a dinuclear structure. Magnetic measurements revealed the antiferromagnetic exchange interaction between the two radicals of the diradical ligand 1 through the pyrazine ring. For complexes 2Gd to 7Yb with the reduced non-radical ligand, their magnetic properties are consistent with the isolated LnIII centers. Alternating-current (ac) magnetic susceptibility investigations indicate that complexes 3Dy and 7Yb exhibit field-induced frequency dependence, which indicates the presence of slow relaxation of the magnetization. Ab initio calculations were performed on these compounds to understand their magnetic anisotropy and their different magnetic dynamics. PMID- 29796501 TI - Chirality in rotaxanes and catenanes. AB - Although chiral mechanically interlocked molecules (MIMs) have been synthesised and studied, enantiopure examples are relatively under-represented in the pantheon of reported catenanes and rotaxanes and the underlying chirality of the system is often even overlooked. This is changing with the advent of new applications of MIMs in catalysis, sensing and materials and the appearance of new methods to access unusual stereogenic units unique to the mechanical bond. Here we discuss the different stereogenic units that have been investigated in catenanes and rotaxanes, examples of their application, methods for assigning absolute stereochemistry and provide a perspective on future developments. PMID- 29796507 TI - An octahedral tetrachlorido Fe(ii) complex with aminopyrazinium ligands from a serendipitous redox synthesis exhibiting magnetic exchange through non-covalent 3 D architectures. AB - An air stable, neutral Fe(ii) complex with four equatorial chlorido ligands has been stabilised through a serendipitous redox process and in situ ligand protonation. A three-dimensional non-covalent network composed of halogen bonding and pi-pi stacking promotes magnetic exchange interactions though the lattice. The electronic structure has been investigated using DFT. PMID- 29796506 TI - Bicapped Keggin polyoxomolybdates: discrete species and experimental and theoretical investigations on the electronic delocalization in a chain compound. AB - Three monomeric polyoxometalates [M(C10H8N2)3][alpha-PMoMoO40Zn2(C10H8N2)2].2H2O (M-PMo12Zn2, M = Fe, Co, Ru) with {Zn(bpy)2}2+ units capped on reduced alpha Keggin polyanions and [M(bpy)3]2+ counter-ions were synthesized under hydrothermal conditions. The 1D polymer [N(C4H9)4][Ru(C10H8N2)3][alpha-PMoMoO43] (Ru-PMo14) was prepared by a similar strategy, in the absence of 2,2'-bpy ligands. In this chain capped reduced Keggin anions are linked via Mo-O-Mo bridges and are surrounded by both tetrabutylammonium cations and [Ru(bpy)3]2+ counter-ions. The compounds were characterized in the solid state by single crystal and powder X-ray diffraction and IR spectroscopy and in solution by 31P NMR spectroscopy. 31P diffusion ordered NMR spectroscopy (DOSY) indicates that the diffusion coefficient of the dissolved species of Ru-PMo14 corresponds to a dimeric structure. Magnetic susceptibility measurements performed on Ru-PMo14 show the existence of antiferromagnetic interactions between the d1 electrons of the six MoV centers, with a singlet spin ground state. However, attempts to fit the data in the 2-300 K temperature range with Heisenberg Hamiltonians adapted for 0 or 1D systems suggest that these electrons are delocalized. Density Functional Theory (DFT) and Wave Function Theory (WFT) calculations indicate a migration of the electrons of the capping MoV centers into the PMo12 units at high temperature, allowing the rationalization of the experimental observations. PMID- 29796508 TI - Synthesis, characterisation and thermal properties of Sn(ii) pyrrolide complexes. AB - SnO is a rare example of a stable p-type semiconductor material. Here, we describe the synthesis and characterisation of a family of Sn(ii) pyrrolide complexes for future application in the MOCVD and ALD of tin containing thin films. Reaction of the Sn(ii) amide complex, [{(Me3Si)2N}2Sn], with the N,N bidentate pyrrole pro-ligand, L1H, forms the hetero- and homoleptic complexes [{L1}Sn{N(SiMe3)2}] (1) and [{L1}2Sn] (2), respectively, bearing the 2 dimethylaminomethyl-pyrrolide ligand (L1). Reaction of [{(Me3Si)2N)}2Sn] with the pyrrole-aldimine pro-ligands, L2H-L7H, results in the exclusive formation of the homoleptic bis-pyrrolide complexes [{L2-7}2Sn] (3-8). All complexes have been characterised by elemental analysis and NMR spectroscopy, and the molecular structures of complexes 1-5 and 8 are determined by single crystal X-ray diffraction. TG analysis and isothermal TG analysis have been used to evaluate the potential utility of these systems as MOCVD and ALD precursors. PMID- 29796509 TI - A high pressure pathway toward boron-based nanostructured solids. AB - Inorganic nanocomposites made of an inorganic matrix containing nanoparticle inclusions provide materials of advanced mechanical, magnetic, electrical properties and multifunctionality. The range of compounds that can be implemented in nanocomposites is still narrow and new preparation methods are required to design such advanced materials. Herein, we describe how the combination of nanocrystal synthesis in molten salts with subsequent heat treatment at a pressure in the GPa range gives access to a new family of boron-based nanocomposites. With the case studies of HfB2/beta-HfB2O5 and CaB6/CaB2O4(iv), we demonstrate by X-ray diffraction and through (scanning) transmission electron microscopy the crystallization of borate matrices into rare compounds and unique nanostructured solids, while metal boride nanocrystals remain dispersed in the matrix and maintain small sizes below 30 nm, thus demonstrating a new multidisciplinary approach toward nanoscaled heterostructures. PMID- 29796510 TI - Oxidative nitrene transfer from azides to alkynes via Ti(ii)/Ti(iv) redox catalysis: formal [2+2+1] synthesis of pyrroles. AB - Catalytic oxidative nitrene transfer from azides with the early transition metals is rare, and has not been observed without the support of redox noninnocent spectator ligands. Here, we report the formal [2+2+1] coupling of azides and alkynes via TiII/TiIV redox catalysis from simple Ti halide imido precatalysts. These reactions yield polysubstituted N-alkyl pyrroles, including N-benzyl protected pyrroles and rare examples of very electron rich pentaalkyl pyrroles. Mechanistic analysis reveals that [2+2+1] reactions with bulky azides have different mechanistic features from previously-reported reactions using azobenzene as a nitrene source. PMID- 29796511 TI - Label-free, high-throughput detection of P. falciparum infection in sphered erythrocytes with digital holographic microscopy. AB - Effective malaria treatment requires rapid and accurate diagnosis of infecting species and actual parasitemia. Despite the recent success of rapid tests, the analysis of thick and thin blood smears remains the gold standard for routine malaria diagnosis in endemic areas. For non-endemic regions, sample preparation and analysis of blood smears are an issue due to low microscopy expertise and few cases of imported malaria. Automation of microscopy results could be beneficial to quickly confirm suspected infections in such conditions. Here, we present a label-free, high-throughput method for early malaria detection with the potential to reduce inter-observer variation by reducing sample preparation and analysis effort. We used differential digital holographic microscopy in combination with two-dimensional hydrodynamic focusing for the label-free detection of P. falciparum infection in sphered erythrocytes, with a parasitemia detection limit of 0.01%. Moreover, the achieved differentiation of P. falciparum ring-, trophozoite- and schizont life cycle stages in synchronized cultures demonstrates the potential for future discrimination of even malaria species. PMID- 29796512 TI - Synthesis of ternary group 13/15 chain compounds. AB - Herein we present the synthesis and characterisation of the seven-membered group 13/15 chain compound HB{N(H)PtBu2BH3}2 (3) obtained from the reaction of tBu2PNH2 (1) with Me2S.BH3. Furthermore, we describe the synthesis of the aluminium and gallium compounds tBu2PN(H)AltBu2N(H)P(H)tBu2 (4) and tBu2(H)PN(H)GatBu3 (5) derived from the reaction of tBu2PNH2 (1) with MtBu3 (M = Al, Ga). PMID- 29796513 TI - A strategy for developing metal-free hydrogenation catalysts: a DFT proof-of principle study. AB - We computationally formulated a metal-free strategy to construct bifunctional active sites for reversible H2 activation, using a N-centered group as a Lewis basic site and a PV-centered group as a Lewis acidic site. By embedding the active sites into five-membered and 6-membered rings, we designed a series of molecules, some of which have feasible kinetic barriers to perform catalytic hydrogenation, calling for experimental realizations. PMID- 29796515 TI - Solvent mediated hybrid 2D materials: black phosphorus - graphene heterostructured building blocks assembled for sodium ion batteries. AB - Here we demonstrate the broad capability to exploit interactions at different length scales in 2D materials to prepare macroscopic functional materials containing hybrid black phosphorus/graphene (BP/G) heterostructured building blocks. First, heterostructured 2D building blocks are self-assembled during co exfoliation in the solution phase based on electrostatic attraction of different 2D materials. Second, electrophoretic deposition is used as a tool to assemble these building blocks into macroscopic films containing these self-assembled 2D heterostructures. Characterization of deposits formed using this technique elucidates the presence of stacked and sandwiched 2D heterostructures, and zeta potential measurements confirm the mechanistic interactions driving this assembly. Building on the exceptional sodium alloying capacity of BP, these materials were demonstrated as superior binder-free and additive-free anodes for sodium batteries with specific discharge capacity of 2365 mA h gP-1 and long stable cycling duration. This study demonstrates how controllable co-processing of 2D materials can enable material control for stacking and building block assembly relevant to broad future applications of 2D materials. PMID- 29796514 TI - The first representatives of tetranuclear gold(i) complexes of P,N-containing cyclophanes. AB - The first representatives of the tetranuclear gold(i) complexes of P,N-containing cyclophanes with two 1,5-diaza-3,7-diphosphacyclooctane rings incorporated into the macrocyclic core have been obtained. The complexation leads to a change in ligand conformations so that the diazadiphosphacyclooctane fragments of the complexes adopt twist-chair conformations, and two of the four gold(i) ions are located over and under the partially collapsed macrocyclic cavity. The complexes demonstrate moderate solid-state green emission. PMID- 29796517 TI - Nanosecond laser flash photolysis of a 6-nitroindolinospiropyran in solution and in nanocrystalline suspension under single excitation conditions. AB - Nanosecond transient absorption spectroscopy was used to study the photochemical ring-opening reaction for a 6-nitroindolinospiropyran (SP1) in solution and in nanocrystalline (NC) suspension at 298 K. We measured the kinetics in argon purged and air saturated acetonitrile and found that the presence of oxygen affected two out of the three components of the kinetic decay at 440 nm. These are assigned to the triplet excited states of the Z- and E-merocyanines (3Z-MC* and 3E-MC*). In contrast, a long-lived growth component at 550 nm and the decay of a band centered at 590 nm showed no dependence on oxygen and are assigned, respectively, to the ground state Z- and E-merocyanines (Z-MC0 and E-MC0). Laser flash photolysis studies performed in NC suspensions initially showed a very broad, featureless absorption spectrum that decayed uniformly for ca. 70 ns before revealing a more defined spectrum that persisted for greater than 4 ms and is consistent with a mixture of the more stable Z- and E-MC0 structures. We performed quantum mechanical calculations on the interconversion of E- and Z-MCs on the S0 and S1 potential energy surfaces. The computed UV-vis spectra for a scan along the Z -> E interconversion reaction coordinate show substantial absorptivity from 300-600 nm, which suggests that the broad, featureless transient absorption spectrum results from the contribution of the transition structure and other high-energy species during the Z to E isomerization. PMID- 29796520 TI - Synthetic studies toward the marine metabolite prorocentin-4: synthesis of the C1 C23 fragment. AB - A synthetic study of the construction of the C1-C23 fragment of prorocentin-4, a novel linear polyketide, is described. The synthetic highlights include the acid catalyzed epoxide opening, Gilman reaction, Pd(OH)2 catalyzed transformation of a primary propargylic alcohol into an aldehyde, Oxa-Michael cyclization, and Horner Wadsworth-Emmons (HWE) olefination reaction as key steps. PMID- 29796523 TI - Microfluidic technologies for circulating tumor cell isolation. AB - Metastasis is the main cause of tumor-related death, and the dispersal of tumor cells through the circulatory system is a critical step in the metastatic process. Early detection and analysis of circulating tumor cells (CTCs) is therefore important for early diagnosis, prognosis, and effective treatment of cancer, enabling favorable clinical outcomes in cancer patients. Accurate and reliable methods for isolating and detecting CTCs are necessary to obtain this clinical information. Over the past two decades, microfluidic technologies have demonstrated great potential for isolating and detecting CTCs from blood. The present paper reviews current advanced microfluidic technologies for isolating CTCs based on various biological and physical principles, and discusses their fundamental advantages and drawbacks for subsequent cellular and molecular assays. Owing to significant genetic heterogeneity among CTCs, microfluidic technologies for isolating individual CTCs have recently been developed. We discuss these single-cell isolation methods, as well as approaches to overcoming the limitations of current microfluidic CTC isolation technologies. Finally, we provide an overview of future innovative microfluidic platforms. PMID- 29796524 TI - From functional structure to packaging: full-printing fabrication of a microfluidic chip. AB - This paper presents a concept of a full-printing methodology aiming at convenient and fast fabrication of microfluidic devices. For the first time, we achieved a microfluidic biochemical sensor with all functional structures fabricated by inkjet printing, including electrodes, immobilized enzymes, microfluidic components and packaging. With the cost-effective and rapid process, this method provides the possibility of quick model validation of a novel lab-on-chip system. In this study, a three-electrode electrochemical system was integrated successfully with glucose oxidase immobilization gel and sealed in an ice channel, forming a disposable microfluidic sensor for glucose detection. This fully-printed chip was characterized and showed good sensitivity and a linear section at a low-level concentration of glucose (0-10 mM). With the aid of automatic equipment, the fully-printed sensor can be massively produced with low cost. PMID- 29796528 TI - Stress resistance and lifespan extension of Caenorhabditis elegans enhanced by peptides from mussel (Mytilus edulis) protein hydrolyzate. AB - Bioactive peptides derived from mussels have multiple healthcare functions. Herein, we aimed to examine the effects of mussel peptide preparation on lifespan, stress resistance, apoptosis and aging in Caenorhabditis elegans. Lifespan was determined by counting the number of surviving nematodes daily. ROS level and lipofuscin were measured using a fluorescent microscope. The mussel protein was prepared and hydrolyzed, and then fractionated by ultrafiltration. The fraction (<3 kDa) was purified by gel filtration to obtain the bioactive peptides, and the peptide sequences included in the fractions were identified, which were mostly composed of peptides with <20 amino acid residues. Mussel peptides treatment was found to significantly increase oxidative stress resistance and extend the lifespan of C. elegans. Moreover, this treatment also reduced endogenous ROS level and aging pigments accumulation in C. elegans as well as apoptosis. Collectively, these findings demonstrated that mussel peptides could contribute to healthspan extension of C. elegans through regulating mRNA expression of daf-2 and daf-16. These results highlighted the important role of mussel peptides for food and pharmaceutical industries to develop new nutraceuticals and functional foods. PMID- 29796529 TI - Phase-shift feedback control for dielectrophoretic micromanipulation. AB - In this paper, we present a novel approach to noncontact micromanipulation by controlled dielectrophoresis (DEP). To steer micro-objects in the desired way, the solutions reported in the literature use either DEP cages or amplitude modulation of the voltages applied to the electrodes. In contrast, we modulate the phases, that is, we control the phase shifts of the voltages applied to the electrodes, which simplifies the hardware implementation and extends the set of feasible forces. Furthermore, we introduce an innovative micro-electrode array layout, composed of four sectors with parallel (colinear) electrodes, which is capable of inducing an arbitrary movement in the manipulation area and is easy to fabricate using just an affordable one-layer technology. We then propose a closed loop cascade control strategy based on real-time numerical optimization and deploy it to our experimental set-up. Numerical simulations and laboratory experiments demonstrate the manipulation capabilities such as positioning and steering of one or several microscopic objects (microspheres with a diameter of 50 MUm) and even bringing two objects together and then separating them again. The results from simulations and experiments are compared and the positioning accuracy is evaluated in the whole manipulation area. The error in position is 8 MUm in the worst case, which corresponds to 16% of the microsphere size or 0.7% of the manipulation range. PMID- 29796530 TI - Supported metal nanoparticles with tailored catalytic properties through sol immobilisation: applications for the hydrogenation of nitrophenols. AB - The use of sol-immobilisation to prepare supported metal nanoparticles is an area of growing importance in heterogeneous catalysis; it affords greater control of nanoparticle properties compared to conventional catalytic routes e.g. impregnation. This work, and other recent studies, demonstrate how the properties of the resultant supported metal nanoparticles can be tailored by adjusting the conditions of colloidal synthesis i.e. temperature and solvent. We further demonstrate the applicability of these methods to the hydrogenation of nitrophenols using a series of tailored Pd/TiO2 catalysts, with low Pd loading of 0.2 wt%. Here, the temperature of colloidal synthesis is directly related to the mean particle diameter and the catalytic activity. Smaller Pd particles (2.2 nm, k = 0.632 min-1, TOF = 560 h-1) perform better than their larger counterparts (2.6 nm, k = 0.350 min-1, TOF = 370 h-1) for the hydrogenation of p-nitrophenol, with the catalyst containing smaller NPs found to have increased stability during recyclability studies, with high activity (>90% conversion after 5 minutes) maintained across 5 catalytic cycles. PMID- 29796531 TI - Modelling free and oxide-supported nanoalloy catalysts: comparison of bulk immiscible Pd-Ir and Au-Rh systems and influence of a TiO2 support. AB - The relative stabilities of different chemical arrangements of Pd-Ir and Au-Rh nanoalloys (and their pure metal equivalents) are studied, for a range of compositions, for fcc truncated octahedral 38- and 79-atom nanoparticles (NPs). For the 38-atom NPs, comparisons are made of pure and alloy NPs supported on a TiO2(110) slab. The relative energies of different chemical arrangements are found to be similar for Pd-Ir and Au-Rh nanoalloys, and depend on the cohesive and surface energies of the component metals. For supported nanoalloys on TiO2, the interaction with the surface is greater for Ir (Rh) than Pd (Au): most of the pure NPs and nanoalloys preferentially bind to the TiO2 surface in an edge-on configuration. When Au-Rh nanoalloys are bound to the surface through Au, the surface binding strength is lower than for the pure Au NP, while the Pd-surface interaction is found to be greater for Pd-Ir nanoalloys than for the pure Pd NP. However, alloying leads to very little difference in Ir-surface and Rh-surface binding strength. Comparing the relative stabilities of the TiO2-supported NPs, the results for Pd-Ir and Au-Rh nanoalloys are the same: supported Janus NPs, whose Ir (Rh) atoms bind to the TiO2 surface, bind most strongly to the surface, becoming closer in energy to the core-shell configurations (Ir@Pd and Rh@Au) which are favoured for the free particles. PMID- 29796532 TI - The simplest supramolecular helix. AB - Diethylamine is the smallest and simplest molecule that features a supramolecular helix as its lowest energy aggregate. Structural studies and large scale sampling simulations show that the helical arrangement is more stable than cyclic structures, which are the dominant species for other small hydrogen bonding molecules. PMID- 29796533 TI - Hypermonins A and B, two 6-norpolyprenylated acylphloroglucinols with unprecedented skeletons from Hypericum monogynum. AB - Two new 6-norpolycyclic polyprenylated acylphloroglucinols (PPAPs), hypermonins A (1) and B (2), featuring an undescribed decahydroindeno[1,7-bc]furan ring system, were isolated from the leaves and twigs of Hypericum monogynum. These compounds are a pair of epimers with opposite configurations at the C-5 position. Their structures, including their absolute configurations, were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway of 1 and 2 was also proposed. Compound 1 exhibited a significant protective effect against corticosterone-induced injury in PC12 cells. PMID- 29796535 TI - Correction: Humic-like substances from urban waste as auxiliaries for photo Fenton treatment: a fluorescence EEM-PARAFAC study. AB - Correction for 'Humic-like substances from urban waste as auxiliaries for photo Fenton treatment: a fluorescence EEM-PARAFAC study' by S. Garcia Ballesteros et al., Photochem. Photobiol. Sci., 2017, 16, 38-45. PMID- 29796541 TI - Engineering enzyme microenvironments for enhanced biocatalysis. AB - Protein engineering provides a means to alter protein structure leading to new functions. Much work has focused on the engineering of enzyme active sites to enhance catalytic activity, however there is an increasing trend towards engineering other aspects of biocatalysts as these efforts can also lead to useful improvements. This tutorial discusses recent advances in engineering an enzyme's local chemical and physical environment, with the goal of enhancing enzyme reaction kinetics, substrate selectivity, and activity in harsh conditions (e.g., low or high pH). By introducing stimuli-responsiveness to these enzyme modifications, dynamic control of activity also becomes possible. These new biomolecular and protein engineering techniques are separate and independent from traditional active site engineering and can therefore be applied synergistically to create new biocatalyst technologies with novel functions. PMID- 29796542 TI - Suppression of dendritic lithium growth in lithium metal-based batteries. AB - Lithium metal-based batteries offer promising prospects as alternatives to today's lithium-ion batteries, due to their ultra-high energy density. Unfortunately, the application of lithium metal is full of challenges and has puzzled researchers for more than 40 years. In this feature article, we describe the history of the development of lithium metal batteries and their existing key challenges, which include non-uniform electrodeposition, volume expansion, high reactivity of the lithium metal/unstable solid electrolyte interphase (SEI), and the shuttling of active cathode materials. Then, we focus on the growth mechanisms of uneven lithium electrodeposition and extend the discussion to the approaches to inhibit lithium dendrites. Finally, we discuss future directions that are expected to drive progress in the development of lithium metal batteries. PMID- 29796544 TI - The challenge of catalyst prediction. AB - New insights and successful use of computational catalysis are highlighted. This is within the context of remaining issues that prevent theoretical catalysis to be fully predictive of catalyst performance. A major challenge is to include in modelling studies the transient initiation as well as deactivation processes of the catalyst. We will illustrate this using as an example for solid acid catalysis, the alkylation process, and for transition metal catalysis, the Fischer-Tropsch reaction. For the alkylation reaction of isobutane and alkene, an important reaction for high octane gasoline, we will present a deactivation model. For the Fischer-Tropsch reaction, which converts synthesis gas into gasoline grade molecules, we discuss structural reorganization of the catalyst induced by reaction. PMID- 29796543 TI - Rhodium-catalyzed asymmetric hydrogenation of beta-branched enamides for the synthesis of beta-stereogenic amines. AB - Using a rhodium complex of a bisphosphine ligand (R)-SDP, beta-branched simple enamides with a (Z)-configuration were hydrogenated to beta-stereogenic amines in quantitative yields and with excellent enantioselectivities (88-96% ee). PMID- 29796545 TI - A pi-conjugated inorganic polymer constructed from boron difluoride formazanates and platinum(ii) diynes. AB - The first example of a pi-conjugated polymer incorporating boron difluoride (BF2) formazanates is introduced. The film-forming properties, controllable reduction chemistry, and low optical band gap (ca. 1.4 eV) of the polymer make it an excellent candidate for use as a light-harvesting n-type semiconductor in organic electronics. Comparison of the polymer to model compounds confirmed that its unique optoelectronic properties can be directly attributed to the presence of the BF2 formazanate repeat unit and that the [Pt(PBu3)2]2+ unit must also be present to achieve the narrow band gaps observed. PMID- 29796546 TI - CO adsorption and oxygen activation on group 11 nanoparticles - a combined DFT and high level CCSD(T) study about size effects and activation processes. AB - The focus of this study lies in the activation of molecular oxygen and reaction with CO within density functional theory (DFT) and high level CCSD(T) calculations. Therefore, we use M13 and M55 nanoparticles (NPs) and periodic M(321) surfaces as model systems and compare the catalytic activity of gold substrates to Ag and Cu based NP catalysts. In the first step, the adsorption energies of CO were compared for nanoparticles of different sizes for Au, Ag and Cu. The adsorption energies on M(321) and M55 NPs (M = Au, Ag, Cu) are virtually identical. For smaller M13 NPs the adsorption energies differ by ~0.2 eV for Ag, ~0.4 eV for Au, and ~0.6 eV for Cu at the PBE level of theory. This can be explained by size effects, as the M13 NPs show a more molecule-like character. Presumably, CO binds more strongly to these very small NPs at the PBE level of theory. However, a benchmark calculation in the framework of CCSD(T)-theory reveals an adsorption energy of CO on Au13 of -0.88 eV, comparable to the adsorption energies calculated at the PBE level for Au55 and Au(321). For Au55, the adsorption energy calculated at the CCSD(T) level is -0.85 eV. This is in perfect agreement with the PBE result. In addition to adsorption energies, dissociation barriers have been calculated on M(321) surfaces. The dissociation energies of O2 on coinage metal catalysts are high, so that direct CO-oxidation reactions with molecular oxygen should be the dominant reaction mechanism compared to the dissociation and reaction of CO and atomic oxygen at least for silver and copper catalysts. PMID- 29796547 TI - Operando study of palladium nanoparticles inside UiO-67 MOF for catalytic hydrogenation of hydrocarbons. AB - Functionalization of metal-organic frameworks with metal nanoparticles (NPs) is a promising way for producing advanced materials for catalytic applications. We present the synthesis and in situ characterization of palladium NPs encapsulated inside a functionalized UiO-67 metal-organic framework. The initial structure was synthesized with 10% of PdCl2bpydc moieties with grafted Pd ions replacing standard 4,4'-biphenyldicarboxylate linkers. This material exhibits the same high crystallinity and thermal stability of standard UiO-67. Formation of palladium NPs was initiated by sample activation in hydrogen and monitored by in situ X-ray powder diffraction and X-ray absorption spectroscopy (XAS). The reduction of PdII ions to Pd0 occurs above 200 degrees C in 6% H2/He flow. The formed palladium NPs have an average size of 2.1 nm as limited by the cavities of UiO-67 structure. The resulting material showed high activity towards ethylene hydrogenation. Under reaction conditions, palladium was found to form a carbide structure indicated by operando XAS, while formation of ethane was monitored by mass spectroscopy and infra-red spectroscopy. PMID- 29796548 TI - Incorporating spin-orbit effects into surface hopping dynamics using the diagonal representation: a linear-response time-dependent density functional theory implementation with applications to 2-thiouracil. AB - In this study, we present a trajectory surface hopping (TSH) method that incorporates spin-orbit (SO) effects using the "diagonal representation" within the Linear-Response Time-Dependent Density Functional Theory (LR-TDDFT) framework. In this approach, the evaluation of spin-orbit coupling (SOC) matrix elements between singlet and triplet states employs the Casida's wave functions and the Breit-Pauli (BP) spin-orbit Hamiltonian with effective charge approximation. The new TSH approach is then used to investigate the excited-state relaxation of 2-thiouracil (2TU) in vacuum and water. On the basis of the simulation results, relaxation of the initially populated bright state is found to be dominated by the route S2 -> S1 -> T. The intersystem crossing (ISC) can occur at either the C2-puckered structure or the C2-pyramidalized S1 minimum, and is promoted by a three-state near-degeneracy (S1/T2/T1 in vacuum or S1/T3/T2 in water) as well as sizable SOCs. Our simulations achieve a good agreement with the available experimental measurements in terms of the internal conversion (IC) and ISC time scales, and complement the picture of the relaxation mechanisms of 2TU after photo-excitation to the first bright state. PMID- 29796549 TI - Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast. AB - Elevated intra-tumoral immune infiltrate is associated with an improved prognosis in cancer of distinct origins. Traniplatin (TPT) is a novel platinum(iv) pro-drug based on Cisplatin (CDDP) and the marketed drug Tranilast. When compared in vitro to Cisplatin, TPT showed increased cytotoxic activity against colon and lung cancer cells but decreased activity against immune cells. In addition, TPT efficiency was evaluated in tumor explants derived from colorectal cancer samples from patients subjected to intended curative surgery. TPT induced strong intra tumoral cytotoxic activity yet was associated with an elevated presence of immune cell infiltrate, suggesting a reduced cytotoxic activity against immune cells in colorectal cancer. PMID- 29796550 TI - Non-covalent interactions of uranyl complexes: a theoretical study. AB - We report a set of theoretical calculations designed to examine the potential of model uranyl complexes to participate in hydrogen- and halogen-bonding. Potential energy scans for the interaction of [UO2Cl2(H2O)3] and [UO2(NCSe)2(H2O)3] with a single water molecule demonstrate that uranyl is a weak hydrogen bond acceptor, but that equatorially coordinated water is a strong hydrogen bond donor. These predictions are supported by a survey of contacts reported in the Cambridge Structural Database. At the minima of each scan, we show that the interaction energy is only weakly dependent on the choice of the theoretical method, with standard density functional theory methods comparing well with coupled-cluster, MP2 and double-hybrid DFT predictions. Geometry optimisation of a 1 : 1 uranyl : water complex results in a cyclic structure, in which vibrational frequencies, atoms-in-molecules and natural bond orbital analysis support the weakness of U Oyl as an acceptor. The origin of this behaviour is traced to the electronic structure of uranyl, and in particular covalency in the U-Oyl bonds resulting from donation into formally empty 5f and 6d orbitals on U. PMID- 29796552 TI - The role of hydrophobic hydration in the LCST behaviour of POEGMA300 by all-atom molecular dynamics simulations. AB - The solubility and lower critical solution temperature (LCST) behaviour of poly(oligo(ethylene glycol)methyl ether methacrylate) (POEGMA300) in water were comprehensively investigated by all-atom molecular dynamics (MD) simulations for 5-, 20-, 50- and 75-mer homopolymers. According to various structural and dynamic properties, the water-solubility of POEGMA300 below the LCST is mainly provided by hydrophobic hydration around the side chain carbon atoms, which is achieved by cage-like water formations. The LCST phase transition occurs when these cage-like structures are disrupted by increasing the temperature above the LCST. During this process, significant amounts of water molecules are released and the local water-ordering is reduced. Moreover, the number of hydrogen bonds and hydrogen bond lifetime results indicate that the hydrogen bonding between polymers and water molecules has relatively little effect on the phase transition. Also, the diffusion rates of 50- and 75-mer POEGMA300 decrease with increasing temperature, which may be due to the breakage of cage-like water structures when the polymer exceeds a certain chain length. Our atomistic level findings will enhance the understanding of the LCST phase transition of OEGMA based homopolymers and will be helpful to design homo- and co-polymers of OEGMAs with required properties. PMID- 29796551 TI - 1-Bromoethene-1-sulfonyl fluoride (BESF) is another good connective hub for SuFEx click chemistry. AB - We demonstrate 1,2-dibromoethane-1-sulfonyl fluoride (DESF) as a bench-stable and readily accessible precursor to the robust SuFEx connector, 1-bromoethene-1 sulfonyl fluoride (BESF). The in situ generation of BESF from DESF opens up several new reaction profiles, including application in the syntheses of unprecedented 3-substituted isoxazole-5-sulfonyl fluorides, 1-substituted-1H 1,2,3-triazole-4-sulfonyl fluorides, 2-amino-1-bromoethane-1-sulfonyl fluorides and 4-bromo-beta-sultams in good to excellent yields. These new modules comprise a pendant sulfonyl fluoride handle, which further undergoes facile and selective SuFEx reactions with a selection of aryl silyl ethers to generate stable and useful sulfonate connections. PMID- 29796553 TI - Hematite/silica nanoparticle bilayers on mica: AFM and electrokinetic characterization. AB - Quantitative studies on self-assembled hematite/silica nanoparticle (NP) bilayers on mica were performed by applying scanning electron microscopy (SEM), atomic force microscopy (AFM), and streaming potential measurements. The coverage of the supporting hematite layers was adjusted by changing the bulk concentration of the suspension and the deposition time. The coverage was determined by direct enumeration of deposited particles from AFM images and SEM micrographs. Afterward, silica nanoparticle monolayers were assembled under diffusion controlled transport. A unique functional relationship was derived connecting the silica coverage with the hematite precursor layer coverage. The formation of the hematite monolayer and the hematite/silica bilayer was also monitored in situ by streaming potential measurements. It was confirmed that the zeta potential of the bilayers was independent of the supporting layer coverage, exceeding 0.15. These measurements were theoretically interpreted in terms of the general electrokinetic model that allowed for deriving a formula for calculating nanoparticle coverage in the bilayers. Additionally, from desorption experiments, the interactions among hematite/silica particles in the bilayers were determined using DLVO theory. These results facilitate the development of a robust method of preparing nanoparticle bilayers with controlled properties, with potential applications in catalytic processes. PMID- 29796554 TI - A luminescent [Pd4Ru8]24+ supramolecular cage. AB - A phosphorescent cage of the form [Pd4Ru8]24+ is reported. The cage was formed using the metalloligand [Ru(dtbubpy)2(qpy)]2+, where qpy = 4,4':2',2'':4'',4''' quaterpyridine and dtbubpy = 4,4'-di-tert-butyl-2,2'-bipyridine. The cage has been characterised by NMR, ESI-MS, TEM and X-ray diffraction analyses and its emission properties elucidated by steady-state and time-resolved emission spectroscopy. PMID- 29796556 TI - Visible-light-activated photoCORMs: rational design of CO-releasing organic molecules absorbing in the tissue-transparent window. AB - To date, most known molecules that release carbon monoxide by the action of light are based on carbonyl complexes of metals. However, they suffer from several disadvantages, so the focus of this perspective is on photoactivatable metal-free CO precursors. The development and design of these systems from the starting point of deep-UV-absorbing hydrophobic molecules and leading to hydrophilic biocompatible visible-light-absorbing CO-releasing molecules (photoCORMs) is described with mechanistic details for several structural motifs. The possibilities of this development are not exhausted and here we discuss the design of new biologically interesting candidates. PMID- 29796555 TI - Formal [4 + 2] cycloaddition of imines with alkoxyisocoumarins. AB - A new preparation of delta-lactams is reported. In the presence of a Lewis acid promoter, alkoxyisocoumarins engage a range of N-aryl and N-alkyl imines to form delta-lactams with a pendent carboalkoxy substituent. A sulfonamide-thiourea catalyst enables the synthesis of these products in moderate to good enantioselectivities. PMID- 29796557 TI - Quo vadis, unimolecular electronics? AB - This paper reviews the present status of unimolecular electronics (UME). The field started in the 1970s with a hope that some day organic molecules (~2 nm in size), when used as electronic components, would challenge Si-based inorganic electronics in ultimate-high-density integrated circuits. The technological push to ever smaller inorganic device sizes (Moore's "law") was driven by a profit motive and by vast investments. UME, the underfunded pauper, may have lost that "race to the bottom", but some excellent science is left to be done. PMID- 29796558 TI - FeCl3 or MeSO3H-promoted multicomponent reactions for facile synthesis of structurally diverse furan analogues. AB - An intriguing conversion of arylglyoxal, cyclic dicarbonyl compounds and phenols to diverse furan analogues under FeCl3 or MeSO3H catalysis is reported. Utilizing this synthetic protocol, a variety of furan analogues could be easily obtained in moderate to good yields with different substituted patterns by varying the reaction medium. Atom-economical characteristics and mild conditions of this method are in accord with the concept of modern green chemistry. PMID- 29796559 TI - Mixed-scale poly(methyl methacrylate) channel network-based single-particle manipulation via diffusiophoresis. AB - Despite the unique advantages of nanochannels imparted by their small size, their utility is limited by the lack of affordable and versatile fabrication methods. Moreover, nanochannel-incorporated fluidic devices require micro-sized conduit integration for efficient access of liquid samples. In this study, a simple and cost-effective fabrication method for mixed-scale channel networks via hot embossing of poly(methyl methacrylate) (PMMA) using a carbon stamp is demonstrated. Due to its high rigidity, PMMA ensures collapse-free channel fabrication. The carbon stamp is fabricated using only batch microfabrication and has a convex architecture that allows the fabrication of a complex channel network via a single imprinting process. In addition, the microchannels are connected to nanochannels via three-dimensional (3D) microfunnels that serve as single-particle-entrapment chambers, ensuring smooth transport of samples into the nanochannels. Owing to the 3D geometry of the microfunnels and the small size of the nanochannels, a solute gradient can be generated locally at the microfunnel. This local solute gradient enables the entrapment of microparticles at the microfunnels via diffusiophoresis, which can manipulate the particle motion in a controllable manner, without any external equipment or additional electrode integration into the channels. To the best of our knowledge, this is the first report of diffusiophoresis-based single-particle entrapment. PMID- 29796560 TI - Anti-staphylococcal biofilm activity of miconazoctylium bromide. AB - We designed and synthesized miconazole analogues containing a substituted imidazolium moiety. The structural modification of the miconazole led to a compound with high potency to prevent the formation and disrupt bacterial biofilms, as a result of accumulation in the biofilm matrix, permeabilization of the bacterial membrane and generation of reactive oxygen species in the cytoplasm. PMID- 29796561 TI - A multiplexed microfluidic system for evaluation of dynamics of immune-tumor interactions. AB - Recapitulation of the tumor microenvironment is critical for probing mechanisms involved in cancer, and for evaluating the tumor-killing potential of chemotherapeutic agents, targeted therapies and immunotherapies. Microfluidic devices have emerged as valuable tools for both mechanistic studies and for preclinical evaluation of therapeutic agents, due to their ability to precisely control drug concentrations and gradients of oxygen and other species in a scalable and potentially high throughput manner. Most existing in vitro microfluidic cancer models are comprised of cultured cancer cells embedded in a physiologically relevant matrix, collocated with vascular-like structures. However, the recent emergence of immune checkpoint inhibitors (ICI) as a powerful therapeutic modality against many cancers has created a need for preclinical in vitro models that accommodate interactions between tumors and immune cells, particularly for assessment of unprocessed tumor fragments harvested directly from patient biopsies. Here we report on a microfluidic model, termed EVIDENT (ex vivo immuno-oncology dynamic environment for tumor biopsies), that accommodates up to 12 separate tumor biopsy fragments interacting with flowing tumor infiltrating lymphocytes (TILs) in a dynamic microenvironment. Flow control is achieved with a single pump in a simple and scalable configuration, and the entire system is constructed using low-sorption materials, addressing two principal concerns with existing microfluidic cancer models. The system sustains tumor fragments for multiple days, and permits real-time, high-resolution imaging of the interaction between autologous TILs and tumor fragments, enabling mapping of TIL-mediated tumor killing and testing of various ICI treatments versus tumor response. Custom image analytic algorithms based on machine learning reported here provide automated and quantitative assessment of experimental results. Initial studies indicate that the system is capable of quantifying temporal levels of TIL infiltration and tumor death, and that the EVIDENT model mimics the known in vivo tumor response to anti-PD-1 ICI treatment of flowing TILs relative to isotype control treatments for syngeneic mouse MC38 tumors. PMID- 29796563 TI - Controlling factors of oligomerization at the water surface: why is isoprene such a unique VOC? AB - Recent studies have shown that atmospheric particles are sufficiently acidic to enhance the uptake of unsaturated volatile organic compounds (VOCs) by triggering acid-catalyzed oligomerization. Controlling factors of oligomerization at the aqueous surfaces, however, remain to be elucidated. Herein, isoprene (2-methyl 1,3-butadiene, ISO), 1,3-butadiene (1,3-b), 1,4-pentadiene (1,4-p), 1-pentene (1 p), and 2-pentene (2-p) vapors are exposed to an acidic water microjet (1 <= pH <= 5), where cationic products are generated on its surface within ~10 MUs and directly detected using surface-sensitive mass spectrometry. We found that carbocations form at the air-water interface in all the cases, whereas the extent of oligomerization largely depends on the structure in the following order: ISO ? 1,3-b > 1,4-p ? 1-p ~ 2-p. Importantly, the cationic oligomerization of ISO yields a protonated decamer ((ISO)10H+, a C50 species of m/z 681.6), while the pentenes 1-p/2-p remain as protonated monomers. We suggest that ISO oligomerization is uniquely facilitated by (1) the resonance stabilization of (ISO)H+ through the formation of a tertiary carbocation with a conjugated C[double bond, length as m-dash]C bond pair, and (2) pi-electron enrichment induced by the neighboring methyl group. Experiments in D2O and D2O : H2O mixtures revealed that ISO oligomerization on the acidic water surface proceeds via two competitive mechanisms: chain-propagation and proton-exchange reactions. Furthermore, we found that ISO carbocations undergo addition to relatively inert 1-p, generating hitherto uncharacterized co-oligomers. PMID- 29796562 TI - Mouse-to-mouse variation in maturation heterogeneity of smooth muscle cells. AB - Smooth muscle cell (SMC) heterogeneity plays an important role in vascular remodeling, a life-threatening hallmark of many vascular diseases. However, the characterization of SMCs at the single-cell level is stymied by drawbacks of contemporary single-cell protein measurements, including antibody probe cross reactivity, chemical fixation artifacts, limited isoform-specific probes, low multiplexing and difficulty sampling cells with irregular morphologies. To scrutinize healthy vessels for subpopulations of SMCs with proliferative-like phenotypes, we developed a high-specificity, multiplexed single-cell immunoblotting cytometry tool for unfixed, uncultured primary cells. We applied our assay to demonstrate maturation stage profiling of aortic SMCs freshly isolated from individual mice. After ensuring unbiased sampling of SMCs (80-120 MUm in length), we performed single-SMC electrophoretic protein separations, which resolve protein signal from off-target antibody binding, and immunoblotted for differentiation markers alpha-SMA, CNN-1 and SMMHC (targets ranging from 34 kDa to 227 kDa). We identified a subpopulation of immature-like SMCs, supporting the recently-established mechanism that only a subset of SMCs is responsible for vascular remodeling. Furthermore, the low sample requirements of our assay enable single-mouse resolution studies, which minimizes animal sacrifice and experimental costs while reporting animal-to-animal phenotypic variation, essential for achieving reproducibility and surmounting the drawbacks of pooling primary cells from different animals. PMID- 29796564 TI - Stabilization of planar tetra-coordinate silicon in a 2D-layered extended system and design of a high-capacity anode material for Li-ion batteries. AB - Stabilization of planar tetra-coordinate silicon (ptSi) was achieved in compounds and 2D-layered extended systems, in which single molecular ptSi in C12H8Si captures four additional electrons to maintain a stable planar structure while the extending conjugate interactions are responsible for the stabilization of ptSi in the 2D sheet. Based on the ptSi SiC12 building block, a SiC8 siligraphene 2D sheet was constructed, and each of its ptSi could accommodate six lithium atoms. The electronic and lithium-storage properties of the ptSi 2D network were explored using first-principles calculations and ab initio molecular dynamics (AIMD) simulations. The newly designed 2D SiC8 sheet has high thermal and dynamic stability, good electronic conductivity, strong lithium-storage ability, a large theoretical capacity of 1297 mA h g-1, and facile surface diffusion of Li and Li+. The predicted relatively high average cell voltages from 2.24 to 2.47 V are fairly stable as the lithium content varies. These unique properties of the 2D SiC8 sheet with ptSi make it quite appealing as a novel anode material for high performance Li-ion batteries (LIBs). PMID- 29796565 TI - Phase-pure pentlandite Ni4.3Co4.7S8 binary sulfide as an efficient bifunctional electrocatalyst for oxygen evolution and hydrogen evolution. AB - Developing an efficient non-noble bifunctional electrocatalyst for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) in the same electrolyte is significant for lowering the cost of electrochemical water splitting. Herein, a phase-pure pentlandite Ni4.3Co4.7S8 bifunctional electrocatalyst was synthesized via a hydrothermal process using a commercial nickel foam as the nickel source. The active metallic nickel source and the chelating agent ethylenediamine play important roles in the formation of phase pure pentlandite Ni4.3Co4.7S8 binary sulfide. Physicochemical characterizations, electrochemical measurements and density functional theory (DFT) computations illustrate that the material has an exposed high-indexed (022) surface with a biomimetic hydrogenase-like structure, and that the pentlandite phase has metallic characteristics, with next-nearest neighbor metal-metal bonds, as well as there being a high overlap of density of state (DOS) at the Fermi-level due to the synergistic effect between Ni and Co ions. In addition, there is an elevation of the d-state center (from -2.84 to -1.52 eV) with high occupation of the anti bonding eg (dx2-y2 and dz2) d-orbitals. These properties endow the Ni4.3Co4.7S8 bifunctional electrocatalyst with higher catalytic activity for OER than RuO2, with comparative activity for HER to commercial Pt/C and with a low over potential for all water splitting in an alkaline electrolyte. The studies here provide a novel strategy to synthesise phase-pure pentlandite nickel cobalt binary sulfides and boost their applications in electrochemical water splitting. PMID- 29796566 TI - Transient imines as 'next generation' directing groups for the catalytic functionalisation of C-H bonds in a single operation. AB - C-H functionalisation promises a paradigm shift in synthetic planning. However, the additional steps often required to install and remove directing groups currently detract from the efficiency. The strategy of reversible installation of a directing group via an imine linkage has recently emerged, with the imine formed and hydrolysed in situ. Such transient directing groups can promote transition metal catalysed functionalisation of unactivated C-H bonds of aldehydes, ketones and amines. This approach removes additional steps usually required for covalent directing groups and can use catalytic quantities of the imine forming component. This review updates the rapidly developing field of transient directing groups for C-H functionalisation on sp2 and sp3 carbon centres, to form new C-C and C-X bonds. We focus on the structures of the transient directing groups as mono or bidentate coordinating groups for various metal catalysts. PMID- 29796567 TI - Characterization of interfacial barrier charging as a resistive switching mechanism in Ag/Sb2Te3/Ag heterojunctions. AB - In this study, bipolar memristive behaviors were systematically characterized in Ag/Sb2Te3/Ag hetero-junctions. By using in situ Raman and photoluminescence spectroscopy, a direct observation of the bonding environment and band structure confirmed that resistive switches are strongly related to the electronic valence changes in Sb2Te3 and the formation of Schottky barriers at Ag/Sb2Te3 interfaces. Band movement of Sb2Te3 acquired by first-principles calculations also supports the electrostatic barrier charging as a memristive mechanism of Ag/Sb2Te3/Ag heterocells. Independent resistance-switching behaviors that can be utilized in both amorphous and crystalline Sb2Te3 lead to multiple resistance values with a large memory window (104-105) and low read voltage (~0.2 V), giving rise to a unique multi-level memory concept. This study based on Ag/Sb2Te3/Ag hetero junctions offers a significant understanding to promote the use of Sb2Te3 and other chalcogenide memristors as promising candidates for compatible high-density memory applications. PMID- 29796569 TI - One pot microwave synthesis of highly stable AuPd@Pd supported core-shell nanoparticles. AB - A series of 1 wt% supported Au, Pd and AuPd nanoalloy catalysts were prepared via microwave assisted reduction of PdCl2 and HAuCl4 in a facile, one pot process. The resulting materials showed excellent activity for the direct synthesis of hydrogen peroxide from hydrogen and oxygen, with a synergistic effect observed on the addition of Au into a Pd catalyst. Detailed electron microscopy showed that the bimetallic particles exhibited a core-shell morphology, with an Au core surrounded by an Au-Pd shell, with a size between 10-20 nm. The presence of Au in the shell was confirmed by EDX studies, with corroborating data from XPS measurements showing a significant contribution of both Au and Pd in the spectra, with the Au signal increasing as the total Au content of the catalyst increased. No PdO was observed, suggesting a complete reduction of the metal chloride nanoparticles. Unlike similar catalysts prepared by sol-immobilisation methodology, the core-shell structures showed excellent stability during the hydrogen peroxide synthesis reaction, and no catalyst deactivation was observed over 4 reuse cycles. This is the first time the preparation of stable core-shell particles have been reported using microwave assisted reduction. The observation that these particles are core-shell, without the need of a complicated synthesis or high thermal treatment and form in just 15 minutes presents an exciting opportunity for this experimental technique. PMID- 29796568 TI - Self-assembly of convex particles on spherocylindrical surfaces. AB - The precise control of assembly and packing of proteins and colloids on curved surfaces has fundamental implications in nanotechnology. In this paper, we describe dynamical simulations of the self-assembly of conical subunits around a spherocylindrical template, and a continuum theory for the bending energy of a triangular lattice with spontaneous curvature on a surface with arbitrary curvature. We find that assembly depends sensitively on mismatches between subunit spontaneous curvature and the mean curvature of the template, as well as anisotropic curvature of the template (mismatch between the two principal curvatures). Our simulations predict assembly morphologies that closely resemble those observed in experiments in which virus capsid proteins self-assemble around metal nanorods. Below a threshold curvature mismatch, our simulations identify a regime of optimal assembly leading to complete, symmetrical particles. Outside of this regime we observe defective particles, whose morphologies depend on the degree of curvature mismatch. To learn how assembly is affected by the nonuniform curvature of a spherocylinder, we also study the simpler cases of assembly around spherical and cylindrical cores. Our results show that both the intrinsic (Gaussian) and extrinsic (mean) curvatures of a template play significant roles in guiding the assembly of anisotropic subunits, providing a rich design space for the formation of nanoscale materials. PMID- 29796570 TI - Nitric oxide release from a cucurbituril encapsulated NO-donor. AB - Controlling S-nitrosothiol decomposition, with the consequent release of nitric oxide, is a topic of great research interest. The incorporation of nitrosomercaptopyridine (SNO+) into the cucurbit[7]uril cavity results in a large increase of its nitrosation equilibrium constant. This effect being a consequence of the preferential stabilization of organic cations by the formation of host : guest complexes with CB7 results in a drastic reduction of the SNO+ denitrosation rate constant. Moreover, SNO+ encapsulation also prevents its decomposition yielding disulfide and nitric oxide. The expulsion of SNO+ from the cucurbituril cavity through the application of a chemical stimulus (competitive binding) results in controlled nitric oxide release as was confirmed by using a NO selective electrode. PMID- 29796571 TI - A theoretical study on the structures and electronic and magnetic properties of new boron nitride composite nanosystems by depositing superhalogen Al13 on the surface of nanosheets/nanoribbons. AB - Inorganic boron nitride (BN) nanomaterials possess outstanding physical and chemical characteristics, and can be considered as an excellent building block to construct new composite nanomaterials. In this work, on the basis of the first principles computations, a new type of composite nanostructure can be constructed by depositing superhalogen Al13 on the surface of low-dimensional BN monolayer or nanoribbons (BNML/BNNRs). All these Al13-modified BN nanosystems can possess large adsorption energies, indicating that superhalogen Al13 can be stably adsorbed on the surface of these BN materials. In particular, it is revealed that independent of the chirality, ribbon width and adsorption site, introducing superhalogen Al13 can endow the BN-based composite systems with a magnetic ground state with a magnetic moment of about 1.00 MUB, and effectively narrow their robust wide band gaps. These new superhalogen-Al13@BN composite nanostructures, with magnetism and an appropriate band gap, can be very promising to be applied in multifunctional nanodevices in the near future. PMID- 29796572 TI - Crossover from semi-dilute to densely packed thin polymer films at the air-water interface and structure formation at thin film breakup. AB - A series of poly(n-butyl acrylate) (PnBA, 5 to 32 kg mol-1) homopolymers and diblock copolymers with poly(ethylene glycol) (PEG, constant molecular weight of 0.3 kg mol-1) is synthesized for the purpose of the investigation of quasi-2D polymer films at the air-water interface. The presented compression isotherms show a transition from theta solvent behavior for PnBA homopolymers to good solvent conditions when the volume fraction of the PEG in the block copolymers is increased by decreasing the molecular weight of PnBA. A transition from a semi dilute regime to a densely packed layer is observed in the pressure isotherms for all the polymers. In the densely packed films we found first evidence for thin film breakup of a thin polymer film directly at the air-water interface. Combination of results from Brewster-Angle-Microscopy and Surface X-ray scattering provide a consistent picture of the film breakup. Our results suggest a preferred length scale of 2.5 MUm. This scenario is analogous to a spinodal mechanism driven by thermal fluctuations of the film height. PMID- 29796573 TI - Influence of Cu adatoms on the molecular assembly of 4,4'-bipyridine on Cu(111). AB - The formation of highly organized structures based on two ligands with pyridyl functionalities, 4,4'-bipyridine (BPY) and 1,4-di(4,4''-pyridyl) benzene (BPYB), and Cu adatoms on the Cu(111) surface has been studied with low temperature and variable temperature scanning tunneling microscopy (STM) and first-principles calculations. We show that the formation of a highly organized adlayer built from adatom-molecule and molecule-molecule units strongly depends on the number of mobile Cu atoms on the surface. While a high concentration of Cu adatoms (high adatom/BPY ratio, >=1) leads systematically to the formation of organometallic nanolines, their absence (low adatom/BPY ratio, ~0) gives a compact self assembled molecular network, and more specifically hydrogen-bond networks (HBN) with BPY molecules organized in a T-shaped fashion. Alternatively, an intermediate concentration of Cu adatoms (0 < adatom/BPY < 1) allows the formation of a well-organized and compact structure where both organometallic and HBN components coexist. Although STM images cannot clearly reveal the presence of Cu adatoms within the organometallic moiety, the bonding of BPY to a single or two Cu adatoms can be clearly identified by scanning tunneling spectroscopy (STS), and is supported by Density Functional Theory (DFT) results. Additional STM simulations suggest that the relative position of the Cu adatom with respect to the organic ligands just above has a significant impact on its detection by STM. This study exemplifies the prominent role of metallic adatoms on the formation of a complex organometallic network and should open more rational practices to optimize the formation of these supramolecular networks. PMID- 29796574 TI - In situ vibrational spectroscopy of adsorbed nitrogen in porous carbon materials. AB - This study uses in situ vibrational spectroscopy to probe nitrogen adsorption to porous carbon materials, including single-wall carbon nanotubes and Maxsorb super activated carbon, demonstrating how the nitrogen Raman stretch mode is perturbed by adsorption. In all porous carbon samples upon N2 physisorption in the mesopore filling regime, the N2 Raman mode downshifts by ~2 cm-1, a downshift comparable to liquid N2. The relative intensity of this mode increases as pressure is increased to saturation, and trends in the relative intensity parallel the volumetric gas adsorption isotherm. This mode with ~2 cm-1 downshift is thus attributed to perturbations arising due to N2-N2 interactions in a condensed film. The mode is also observed for the activated carbon at 298 K, and the relative intensity once again parallels the gas adsorption isotherm. For select samples, a mode with a stronger downshift (>4 cm-1) is observed, and the stronger downshift is attributed to stronger N2-carbon surface interactions. Simulations for a N2 surface film support peak assignments. These results suggest that N2 vibrational spectroscopy could provide an indication of the presence or absence of porosity for very small quantities of samples. PMID- 29796575 TI - Evaluation of prevalence, biochemical profile, and drugs associated with chronic kidney disease-mineral and bone disorder in 11 dialysis centers. AB - INTRODUCTION: The diagnosis and treatment of mineral and bone disorder of chronic kidney disease (CKD-MBD) is a challenge for nephrologists and health managers. The aim of this study was to evaluate the prevalence, biochemical profile, and drugs associated with CKD-MBD. METHODS: Cross-sectional study between July and November 2013, with 1134 patients on dialysis. Sociodemographic, clinical, and laboratory data were compared between groups based on levels of intact parathyroid hormone (iPTH) (< 150, 150-300, 301-600, 601-1000, and > 1001 pg/mL). RESULTS: The mean age was 57.3 +/- 14.4 years. The prevalence of iPTH < 150 pg/mL was 23.4% and iPTH > 601 pg/mL was 27.1%. The comparison between the groups showed that the level of iPTH decreased with increasing age. Diabetic patients had a higher prevalence of iPTH < 150 pg/mL (27.6%). Hyperphosphatemia (> 5.5 mg/dL) was observed in 35.8%. Calcium carbonate was used by 50.5%, sevelamer by 14.7%, 40% of patients had used some form of vitamin D and 3.5% used cinacalcet. Linear regression analysis showed a significant negative association between iPTH, age, and diabetes mellitus and a significant positive association between iPTH and dialysis time. CONCLUSION: The prevalence of patients outside the target for iPTH was 50.5%. There was a high prevalence of hyperphosphatemia (35.8%), and the minority of patients were using active vitamin D, vitamin D analogs, selective vitamin D receptor activators, and cinacalcet. These data indicate the need for better compliance with clinical guidelines and public policies on the supply of drugs associated with CKD-MBD. PMID- 29796576 TI - Clinical and laboratory features of urinary tract infections in young infants. AB - INTRODUCTION: Urinary tract infection (UTI) is the most common serious bacterial infection in young infants. Signs and symptoms are often nonspecific. OBJECTIVES: To describe clinical, demographic and laboratory features of UTI in infants <= 3 months old. METHODS: Cross-sectional study of infants <= 3 months old with UTI diagnosed in a pediatric emergency department, for the period 2010-2012. UTI was defined as >= 50,000 colony-forming units per milliliter of a single uropathogen isolated from bladder catheterization. Paired urinalysis and urine culture from group culture-positive and group culture-negative were used to determine the sensitivity and specificity of pyuria and nitrite tests in detecting UTI. RESULTS: Of 519 urine cultures collected, UTI was diagnosed in 65 cases (prevalence: 12.5%); with male predominance (77%). The most common etiologies were Escherichia coli (56.9%), Klebsiella pneumoniae (18.5%) and Enterococcus faecalis (7.7%). Frequent clinical manifestations were fever (77.8%), irritability (41.4%) and vomiting (25.4%). The median temperature was 38.7 degrees C. The sensitivity of the nitrite test was 30.8% (95%CI:19.9-43.4%), specificity of 100% (95%CI:99.2-100%). Pyuria >= 10,000/mL had a sensitivity of 87.7% (95%CI:77.2-94.5%), specificity of 74.9% (95%CI:70.6 -78.8%). The median peripheral white blood cell count was 13,150/mm3; C-reactive protein levels were normal in 30.5% of cases. CONCLUSIONS: The male: female ratio for urinary tract infection was 3.3:1. Non-Escherichia coli etiologies should be considered in empirical treatment. Fever was the main symptom. Positive nitrite is highly suggestive of UTI but has low sensitivity; whereas pyuria >= 10,000/mL revealed good sensitivity, but low specificity. Peripheral white blood cell count and C reactive protein concentration have limited usefulness to suggest UTI. PMID- 29796577 TI - Sepsis-like histoplasmosis in a kidney transplant patient. AB - Histoplasmosis is a fungus infection that mainly affects immunosuppressed patients. The authors present a case of a kidney transplant recipient who developed sepsis-like histoplasmosis, na atypical but severe manifestation of the disease. The fungus was found in blood and in a skin biopsy, and the treatment with liposomal amphotericin resulted in hepatotoxicity. PMID- 29796579 TI - Renal oncocytoma in a kidney transplant patient: the imaging features on contrast enhanced ultrasonography (CEUS): a case report. AB - Renal oncocytoma is an infrequently reported renal neoplasm, often asymptomatic, which usually behaves as a benign entity and is identified accidentally on radiological imaging. Transplant patients under long-term immunosuppressive drugs have a high prevalence of cancers, such as skin cancers, lymphoproliferative disorders, and renal carcinomas. We present a case report of an asymptomatic renal oncocytoma in a kidney transplant recipient presenting persistent hematuria. The features of computed tomography and contrast-enhanced ultrasound (CEUS) are presented. This was the first time we used CEUS in a transplant kidney recipient presenting a renal mass, allowing the real-time visualization of contrast-enhancement patterns during all vascular phases for the differential diagnosis of renal tumors. Although the pattern of intense vascularization could mislead to an early judgment as a malignant lesion, it could help to exclude other renal lesions without inducing nephrotoxicity. PMID- 29796578 TI - Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study. AB - INTRODUCTION: BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial. OBJECTIVE: To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients. METHODS: This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis. RESULTS: A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83. CONCLUSION: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community. PMID- 29796580 TI - Does high intensity exercise affects irisin plasma levels in hemodialysis patients? A pilot study. AB - BACKGROUND: Irisin is a recently identified exercise-induced hormone that stimulates the "browning" of the white adipose tissue, at least in mice. In chronic kidney disease (CKD) patients, irisin regulation is not fully understood, and little attention has been given to the effects of exercise on irisin levels in these patients. The purpose of this study was to assess the effects of high intensity exercise on irisin plasma levels in CKD patients under hemodialysis (HD). METHODS: Fifteen HD patients (5 men, 44.4 +/- 15.1 years old) were studied and served as their own controls. High intensity (single session) intradialytic strength exercises consisted of three sets of ten repetitions with four different movements in both lower limbs during 30 minutes. Blood samples were collected on different days (exercise and non-exercise day) at exactly the same time (30 and 60 minutes after the start of dialysis session). Plasma irisin levels were measured by ELISA assay and anthropometric and biochemical parameters were evaluated. RESULTS: Irisin plasma levels were significantly reduced in both exercise day (125.0 +/- 18.5 to 117.4 +/- 15.0 ng/mL, p=0.02) and non-exercise day (121.5 +/- 13.7 to 115.4 +/- 17.2 ng/mL, p=0.02) after 60 minutes of dialysis. CONCLUSION: These data suggest that intense intradialytic strength exercise was unable to increase the circulating concentration of irisin in HD patients. Moreover, our data show that after one hour of dialysis session, irisin plasma levels may be reduced. PMID- 29796581 TI - Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology. AB - Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma. PMID- 29796582 TI - Oral infection by Pseudomonas aeruginosa in patient with chronic kidney disease - a case report. AB - Chronic renal patients are more susceptible to hospital complications and infections such as urinary tract infections, peritonitis, surgery infections, and bacteremia, which are often caused by Pseudomonas aeruginosa. A case of a HIV positive girl with chronic kidney disease and with serious oral lesions due to P. aeruginosa septic shock is presented. The patient showed necrotic lesions in the oral mucosa, pathological tooth mobility, bone loss, and hematogenous osteomyelitis in the maxilla. The patient was submitted to systemic antibiotic therapy based on screening culture and treatment of bone lesions by eliminating the causal agent and restoring health conditions. This case report is extremely important for health professionals, since the oral cavity can be affected by this pathogen or serve as a colonization site. PMID- 29796583 TI - Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers. AB - INTRODUCTION: Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS. OBJECTIVE: A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed. METHODS: Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers. RESULTS: A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. CONCLUSION: The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH. PMID- 29796584 TI - Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion. AB - INTRODUCTION: Ischemia-reperfusion (IR) injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN) might attenuate IR renal injury. OBJECTIVE: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. METHODS: Male Wistar rats were distributed into six groups (N=6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR) and maintained until animal sacrifice (48h after surgery). We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. RESULTS: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. CONCLUSION: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress. PMID- 29796585 TI - Posterior reversible leukoencephalopathy syndrome (PRES) after kidney transplantation: a case report. AB - INTRODUCTION: Posterior reversible leukoencephalopathy syndrome (PRES) was first described by Hinchey in 1996. The syndrome is characterized by altered level of consciousness, headache, visual changes, and seizures associated with a vasogenic edema of the white matter that occurs predominantly in the occipital and parietal lobes. Imaging tests such as computed tomography (CT) and especially magnetic resonance imaging (MRI) support the diagnosis. CASE REPORT: We report a case of a 48-year-old female patient who underwent a deceased donor kidney transplant and received tacrolimus as a part of the immunosuppressive regimen. Five weeks after transplantation she was admitted to the emergency due to sudden onset of confusion, disorientation, visual disturbances, and major headache. PRES was suspected and the diagnosis confirmed by brain MRI. Tacrolimus was withdrawn and rapid improvement of the neurological signs occurred leading to the conclusion that this drug triggered the syndrome. CONCLUSION: PRES is an unusual complication after organ transplantation and should be considered in the appropriate clinical setting. Physicians must be aware of this condition in order to provide early detection and appropriate treatment since delay in removing the cause may lead to permanent sequelae. PMID- 29796586 TI - Pp65 antigenemia and cytomegalovirus diagnosis in patients with lupus nephritis: report of a series. AB - INTRODUCTION: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). OBJECTIVE: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. METHODS: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. RESULTS: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 +/- 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. CONCLUSIONS: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients. PMID- 29796587 TI - First stages chronic kidney disease have mild effects on cognitive performance. Results of a 15,105 brazilian adult baseline cohort. AB - INTRODUCTION: The aging of the population may lead to an increased prevalence of dementia and chronic kidney disease (CKD) and their overlap. OBJECTIVE: We investigated the association between CKD and cognitive performance among Brazilian adults (35-74 years). METHODS: Baseline data analysis of the Longitudinal Study of Adults (ELSA-Brasil), a multicenter cohort comprising 15,105 civil servants, was performed. Kidney function was defined by the CKD-Epi estimated GRF and albumin creatinin ratio (ACR). Cognitive performance was measured across tests that included the word memory tests, verbal fluency tests and Trail Making Test B. Multiple logistic and linear regressions were used to investigate the association between CKD and global as well as test-specific lowered cognitive performance. RESULTS: More than 90% of participants did not present CKD even considering reduced GFR or increased ACR simultaneously. Lowered cognitive performance was detected among 15.8% of the participants and mean values of GFR were slightly higher among those with normal than with lowered cognitive performance (86 +/- 15 mL/min/1.73 m2 x 85 +/- 16 mL/min/1.73 m2, p < 0.01). Age, education, skin-color, smoking, drinking, hypertension, and diabetes were associated with lowered cognition. After adjustment for these variables, there was no association between CKD and lowered cognitive performance. Negligibly small beta values were observed when analyzing CKD and the scores of all tests. CONCLUSION: These results suggest that cognitive performance remains preserved until renal function reaches significant worsening. Preventive measures to maintain renal function may contribute to the preservation of cognitive function. PMID- 29796588 TI - CKD-MBD in Brazil: the gap between reality and the recommended guidelines. PMID- 29796589 TI - Fear Odor Facilitates the Detection of Fear Expressions Over Other Negative Expressions. AB - In a double-blind experiment, participants were exposed to facial images of anger, disgust, fear, and neutral expressions under 2 body odor conditions: fear and neutral sweat. They had to indicate the valence of the gradually emerging facial image. Two alternative hypotheses were tested, namely a "general negative evaluative state" hypothesis and a "discrete emotion" hypothesis. These hypotheses suggest 2 distinctive data patterns for muscle activation and classification speed of facial expressions. The pattern of results that would support a "discrete emotions perspective" would be expected to reveal significantly increased activity in the medial frontalis (eyebrow raiser) and corrugator supercilii (frown) muscles associated with fear, and significantly decreased reaction times (RTs) to "only" fear faces in the fear odor condition. Conversely, a pattern of results characterized by only a significantly increased corrugator supercilii activity together with decreased RTs for fear, disgust, and anger faces in the fear odor condition would support an interpretation in line with a general negative evaluative state perspective. The data support the discrete emotion account for facial affect perception primed with fear odor. This study provides a first demonstration of perception of discrete negative facial expressions using olfactory priming. PMID- 29796590 TI - Safe working in a 7-day service. Experience of hip fracture care as documented by the UK National Hip Fracture Database. AB - Objective: to describe differences in care and 30-day mortality of patients admitted with hip fracture on weekends (Saturday-Sunday) compared to weekdays (Monday-Friday), and their relationship to the organisation of care. Methods: data came from the National Hip Fracture Database (NHFD) linked to ONS mortality data on 52,599 patients presenting to 162 units in England between 1 January and 31 December 2014. This was combined with information on geriatrician staffing and major trauma centre (MTC) status. 30-day mortality and care were compared for patients admitted at weekends and weekdays; separately for patients treated in units grouped by the mean level of input by geriatricians, weekend geriatrician clinical cover and MTC status. Differences were adjusted for variation in patients' characteristics. Results: there was no evidence of differences in 30 day mortality between patients admitted at weekends compared to weekdays (7.2 vs 7.5%, P = 0.3) before or after adjusting for patient characteristics in either MTCs or general hospitals. The proportion receiving a preoperative geriatrician assessment was lower at weekends (42.8 vs 60.7%, P < 0.001). 30-day mortality was lower in units with higher levels of geriatrician input, but there was no weekend mortality effect associated with lower levels of input or absence of weekend cover. Conclusion: there was no evidence of a weekend mortality effect among patients treated for hip fracture in the English NHS. It appears that clinical teams provide comparably safe and effective care throughout the week. However, greater geriatrician involvement in teams was associated with overall lower mortality. PMID- 29796591 TI - Corrigendum: Preterm Birth Changes Networks of Newborn Cortical Activity. PMID- 29796593 TI - What is the agronomic potential of biofertilizers for maize? A meta-analysis. AB - Biofertilizers are promoted as a strategy for sustainable intensification of agriculture, but their efficacy varies widely among published studies and it is unclear whether they deliver the promised benefits. Studies are commonly conducted under controlled conditions prior to deployment in the field, yet the predictive value of such studies for field-scale productivity has not been critically examined. A meta-analysis was conducted using a novel host crop specific approach to evaluate the agronomic potential of bacterial biofertilizers for maize. Yield increases tended to be slightly higher and more variable in greenhouse studies using field soil than in the field, and greenhouse studies poorly predicted the influence of moderating climate, soil and taxonomic variables. We found greater efficacy of Azospirillum spp. and lower efficacy of Bacillus spp. and Enterobacter spp. under field conditions. Surprisingly, biofertilizer strains with confirmed plant-growth-promoting traits such as phosphorus solubilization, nitrogen fixation and phytohormone production in vitro were associated with lower yields in the field than strains not confirmed to possess these traits; only 1-aminocyclopropane-1-carboxylate deaminase synthesis increased yields. These results indicate the need for a novel biofertilizer development framework that integrates information from native soil microbial communities and prioritizes field validation of results. PMID- 29796592 TI - Endothelial Insulin Receptor Restoration Rescues Vascular Function in Male Insulin Receptor Haploinsufficient Mice. AB - Reduced systemic insulin signaling promotes endothelial dysfunction and diminished endogenous vascular repair. We investigated whether restoration of endothelial insulin receptor expression could rescue this phenotype. Insulin receptor knockout (IRKO) mice were crossed with mice expressing a human insulin receptor endothelial cell-specific overexpression (hIRECO) to produce IRKO-hIRECO progeny. No metabolic differences were noted between IRKO and IRKO-hIRECO mice in glucose and insulin tolerance tests. In contrast with control IRKO littermates, IRKO-hIRECO mice exhibited normal blood pressure and aortic vasodilatation in response to acetylcholine, comparable to parameters noted in wild type littermates. These phenotypic changes were associated with increased basal- and insulin-stimulated nitric oxide production. IRKO-hIRECO mice also demonstrated normalized endothelial repair after denuding arterial injury, which was associated with rescued endothelial cell migration in vitro but not with changes in circulating progenitor populations or culture-derived myeloid angiogenic cells. These data show that restoration of endothelial insulin receptor expression alone is sufficient to prevent the vascular dysfunction caused by systemically reduced insulin signaling. PMID- 29796595 TI - Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. AB - Background: If HIV patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is crushed and dissolved prior to administration. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq(r), referred to as TRI); therefore, crushing of TRI is not recommended. Objectives: To investigate whether the TRI fixed-dose combination tablet can be crushed and combined with enteral nutrition without influencing pharmacokinetics (PK). Methods: We carried out an open-label, three-period, randomized, single-dose, crossover trial in 22 healthy adult volunteers. Subjects randomly received whole-tablet TRI with fasting (reference), crushed and suspended TRI with fasting or crushed and suspended TRI with oral intake of enteral nutrition. Bioequivalence criteria (80%-125% acceptance range) of AUC0-infinity and Cmax were used. ClinicalTrials.gov: NCT02569346. Results: Crushing TRI leads to higher dolutegravir exposure (AUC0-infinity: +26% and Cmax: +30%) and, if crushed TRI is combined with enteral nutrition, to a decrease in abacavir Cmax (-17%). Lamivudine concentrations were not affected as geometric mean ratios with 90% CIs fell within the 80%-125% range. Conclusions: Bioequivalence could not be demonstrated for a crushed and suspended tablet or a crushed and suspended tablet with oral intake of enteral nutrition compared with whole-tablet TRI with fasting. Both scenarios led to higher dolutegravir exposure, but this did not exceed exposure after intake with food or in twice daily dosing. In our opinion, TRI can be crushed for patients with swallowing difficulties and can be simultaneously administered with enteral nutrition. PMID- 29796594 TI - Streptococcal Siglec-like adhesins recognize different subsets of human plasma glycoproteins: implications for infective endocarditis. AB - Streptococcus gordonii and Streptococcus sanguinis are typically found among the normal oral microbiota but can also cause infective endocarditis. These organisms express cell surface serine-rich repeat adhesins containing "Siglec-like" binding regions (SLBRs) that mediate attachment to alpha2-3-linked sialic acids on human glycoproteins. Two known receptors for the Siglec-like adhesins are the salivary mucin MG2/MUC7 and platelet GPIbalpha, and the interaction of streptococci with these targets may contribute to oral colonization and endocarditis, respectively. The SLBRs display a surprising diversity of preferences for defined glycans, ranging from highly selective to broader specificity. In this report, we characterize the glycoproteins in human plasma recognized by four SLBRs that prefer different alpha2-3 sialoglycan structures. We found that the SLBRs recognize a surprisingly small subset of plasma proteins that are extensively O glycosylated. The preferred plasma protein ligands for a sialyl-T antigen selective SLBR are proteoglycan 4 (lubricin) and inter-alpha-trypsin inhibitor heavy chain H4. Conversely, the preferred ligand for a 3'sialyllactosamine selective SLBR is glycocalicin (the extracellular portion of platelet GPIbalpha). All four SLBRs recognize C1 inhibitor but detect distinctly different glycoforms of this key regulator of the complement and kallikrein protease cascades. The four plasma ligands have potential roles in thrombosis and inflammation, and each has been cited as a biomarker for one or more vascular or other diseases. The combined results suggest that the interaction of Siglec-like adhesins with different subsets of plasma glycoproteins could have a significant impact on the propensity of streptococci to establish endocardial infections. PMID- 29796596 TI - The Effects of a Single Electronic Music Improvisation Session on the Pain of Adults with Sickle Cell Disease: A Mixed Methods Pilot Study. AB - Background: Adults with sickle cell disease (SCD) experience acute pain that is multidimensional. Despite recent improvements in treatment, pain management remains a significant challenge for these individuals. Music therapy interventions have the potential to address several dimensions of SCD pain, but they require systematic investigation. Objective: This study investigated feasibility and preliminary efficacy of a single-session electronic music improvisation with a music therapist to diminish pain intensity and improve pain relief and mood in adults with SCD. Methods: Using a three-group mixed methods intervention design, we randomized 60 adults with SCD to standard care plus one of three 20-minute study conditions: 1) electronic music improvisation with a music therapist (MT); 2) recorded music listening (ML); or 3) no intervention (control). Measures of pain intensity (VASPI), pain relief (VASPR), and mood (VASMOOD) were assessed before and after the study conditions, with a subset of MT and ML participants interviewed after measure completion. Results: Compared to control, MT produced significant improvements in VASPI (odds ratio (OR) = 5.12, P = 0.035) and VASMOOD (OR = 11.60, P = 0.005). ML produced significant improvements in VASMOOD compared to control (OR = 5.76, P = 0.040). Qualitatively, there were two prominent themes directly related to music: 1) ML and MT offered many positive and few negative effects; and 2) music therapists provided comfort beyond the music. Conclusions: Preliminary findings were promising and support the need for additional studies evaluating improvisational music therapy interventions for acute pain management in adults with SCD. PMID- 29796597 TI - Dental Injuries in a Sample of Portuguese Militaries - A Preliminary Research. AB - Introduction: Traumatic dental and maxillofacial injuries are very common and appear to affect approximately 20-30% of permanent dentition, with often serious psychological, economic, functional, and esthetic consequences. Militaries are a highest risk group for orofacial trauma, not only because they are constantly engaged in physical activity (which increase the risk of traumatic injuries) but also because they are exposed to many risk factors. The aim of this study was to evaluate the prevalence of orofacial injuries, militaries knowledge about first aid procedures following a dental avulsion and the use of mouthguards in a sample of Portuguese militaries. Materials and Methods: An observational cross-sectional study was conducted for forces of the Infantry Regiment n degrees 14 of Viseu, Portugal. The study involved 122 members of the armed forces who were asked to complete a questionnaire, which enquired about: the occurrence of dental trauma, the use of mouthguards and militaries knowledge with regard to first-aid management of dental avulsions. Results: In our sample, 5.7% reported having experienced a dental trauma. This was further broken down to reveal that 2.5% had experienced an avulsion and 3.3% had a dental fracture. All respondents who reported having suffered dental trauma, reported that this was the only time that they had experienced dental trauma. Within this group, 71.4% visited a dentist, however only one (20%) visited the dentist during the same day that the trauma occurred. In addition, 21.3% mentioned that they had seen a dental trauma in at least one colleague during military trainings/operations. In the case of dental avulsion, the majority (54.9%) did not know how to act. The rate of mouthguard's use among militaries was very low (6.4%). The main reason reported for not using a mouthguard was thinking that it is not necessary (53.3%). Besides that, 31.1% did not know what a mouthguard was for. Conclusion: Prevention programs and promoting actions with this population are important reflections and should be adopted to reduce the incidence of orofacial trauma and to increase knowledge about this topic. PMID- 29796598 TI - Emergence of XDR Escherichia coli carrying both blaNDM and mcr-1 genes in chickens at slaughter and the characterization of two novel blaNDM-bearing plasmids. PMID- 29796599 TI - The impact of a sugar-sweetened beverages tax on oral health and costs of dental care in Australia. AB - Background: Despite a clear causal link between frequent consumption of sugar sweetened beverages (SSBs) and dental disease, little is known about the implications of a tax on SSBs in the context of oral health. The aim of our study was to estimate the impacts of a SSB tax on the Australian population in the context of oral health outcomes, dental care utilisation and associated costs. Methods: We designed a cohort model that accounted for the consequences of the tax through the mechanisms of consumer response to price increase, the effect on oral health due to change in sugar intake, and the implications for dental care use. Results: Our results indicate that in the adult population an ad valorem tax of 20% would lead to a reduction in decayed, missing and filled teeth (DMFT) by 3.9 million units over 10 years, resulting in cost savings of A$666 million. Scenario analyses show that the outcomes are sensitive to the choice of the time horizon, tax rate, price elasticity of demand for SSBs, and the definition of target population. Conclusion: We found that the total and per-person consequences of SSB tax were considerable, both in terms of dental caries (tooth decay) averted and dental care avoided. These results have to be compounded with the implications of SSB tax for other aspects of health and health care, especially in the context of chronic diseases. On the other hand, the improved outcomes have to be weighted against a welfare loss associated with introducing a tax. PMID- 29796600 TI - The successful use of subcutaneous abatacept in refractory anti- human transcriptional intermediary factor 1-gamma dermatomyositis skin and oesphagopharyngeal disease. PMID- 29796601 TI - Proteinuria-associated renal magnesium wasting leads to hypomagnesemia: a common electrolyte abnormality in chronic kidney disease. AB - Background: Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. Methods: In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. Results: In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was >=0.3 g/gCre (Pinteraction=0.001). Conclusions: Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD. PMID- 29796602 TI - Analysis of pathogenicity and immune efficacy of fowl adenovirus serotype 4 isolates. AB - In the present study, the pathogenicity of fowl adenovirus (FAdV) serotype 4 strain HB1501 was systematically determined by using different doses and routes of inoculation in chickens and assessed the immune efficacy induced by fowl adenovirus serotype 4 (FAdV-4) strain SB15 in a vaccination trial. The results revealed that strain HB1501 was highly virulent in chickens, inflicting 30 to 100% mortality when administered by intramuscular and intravenous routes, and its pathogenicity was influenced markedly by the inoculation route. The inactivated oil-emulsion FAdV-4 vaccine derived from strain SB15 completely protected specific pathogen-free chickens against morbidity and mortality following infection with the virulent FAdV-4 strain HB1501. Importantly, no obvious clinical signs or gross lesions were observed and high antibody levels against FAdV were measured in the SB15-vaccinated chickens, indicating the potential of this strain to become an alternative vaccine candidate. This study provides detailed information on the pathogenicity of FAdV-4, which should be of great value to the control of hepatitis-hydropericardium syndrome. PMID- 29796604 TI - Travel-related risk factors for coccidioidomycosis. AB - Background: Coccidioidomycosis is a regionally endemic systemic mycosis with unique risk factors. Since people travel for business or pleasure, and often in conjunction with their avocations or hobbies, the objectives of this review were to describe these and other risk factors for coccidioidomycosis; to alert travel medicine clinicians to the different presenting manifestations of coccidioidomycosis; and to recommend effective treatment, disease control and prevention strategies. Methods: To meet the objectives of this review, Internet search engines were queried with the keywords as medical subject headings over the study period, 1970-2017. Results: The principle transmission mechanism of coccidioidomycosis is by deep inhalation of aerosolized arthroconidia with resulting symptomatic pulmonary infections ranging from febrile influenza-like illnesses to fatal disseminated mycoses. In addition to residency or travel in endemic areas, persons immunocompromised by advancing age, pregnancy, cancer, corticosteroid therapy, diabetes, organ transplantation and human immunodeficiency virus infection are at significantly increased risks of contracting coccidioidomycosis. Persons of African, Asian, Filipino and Hispanic descent are also at increased risks of contracting coccidioidomycosis. Hobbies associated with coccidioidomycosis have included armadillo hunting, model airplane flying and archaeological digging. Occupational risk factors for coccidioidomycosis include endemic exposures during military maneuvers, outdoor track and field events, road construction, solar-power and wind-power farm construction, archaeological excavation and prison work. Conclusions: Coccidioidomycosis is more common in endemic and non-endemic areas than previously recognized and can result in considerable morbidity and mortality. Coccidioidomycosis is increasingly imported from endemic areas in the Western Hemisphere to non-endemic areas worldwide. Increased awareness of disease risk factors among the public and the international healthcare community will improve the timely diagnosis and treatment of coccidioidomycosis and prevent disease progression, dissemination and deaths in residents in and in travellers returning from endemic regions. A vaccine for the primary prevention of coccidioidomycosis would be cost-effective. PMID- 29796603 TI - Factors Associated with Migraine in the General Population of Spain: Results from the European Health Survey 2014. AB - Objective: To identify the modifiable and nonmodifiable variables that are associated with and might moderate the presence of migraine in the general population. Design: Nationally representative cross-sectional survey. Setting: Noninstitutionalized population of Spain. Subjects: Individuals aged 15 years or older (N = 22,842). Methods: A secondary analysis of data from the second wave of the European Health Interview Survey conducted in Spain (2014/2015). We estimated the prevalence of migraine and its distribution according to the study variables, and then built a multivariate logistic model encompassing age, sex, depression severity, chronic anxiety, body mass index, physical activity, smoking status, alcohol use, and perceived social support to predict migraine. Results: The one year prevalence of migraine was 8%. The final multivariate model (Wald chi2 = 693.00, df = 15, P < 0.001) retained depression severity, chronic anxiety, exercising several times a month or week, and alcohol use as predictors of migraine (odds ratios = 2.1-3.5 for positive associations, odds ratios = 0.4-0.9 for negative associations). Conclusions: Raising awareness among clinicians regarding the fact that many of the variables that potentially contribute to the presence of migraine are modifiable (e.g., psychological problems and lifestyle behaviors) might intensify resources dedicated to assessing and impacting these factors in order to potentially prevent the frequency and severity of migraine. PMID- 29796605 TI - Cost savings associated with an alternative payment model for integrating behavioral health in primary care. AB - Financially supporting and sustaining behavioral health services integrated into primary care settings remains a major barrier to widespread implementation. Sustaining Healthcare Across Integrated Primary Care Efforts (SHAPE) was a demonstration project designed to prospectively examine the cost savings associated with utilizing an alternative payment methodology to support behavioral health services in primary care practices with integrated behavioral health services. Six primary care practices in Colorado participated in this project. Each practice had at least one on-site behavioral health clinician providing integrated behavioral health services. Three practices received non-fee for-service payments (i.e., SHAPE payment) to support provision of behavioral health services for 18 months. Three practices did not receive the SHAPE payment and served as control practices for comparison purposes. Assignment to condition was nonrandom. Patient claims data were collected for 9 months before the start of the SHAPE demonstration project (pre-period) and for 18 months during the SHAPE project (post-period) to evaluate cost savings. During the 18-month post period, analysis of the practices' claims data demonstrated that practices receiving the SHAPE payment generated approximately $1.08 million in net cost savings for their public payer population (i.e., Medicare, Medicaid, and Dual Eligible; N = 9,042). The cost savings were primarily achieved through reduction in downstream utilization (e.g., hospitalizations). The SHAPE demonstration project found that non-fee-for-service payments for behavioral health integrated into primary care may be associated with significant cost savings for public payers, which could have implications on future delivery and payment work in public programs (e.g., Medicaid). PMID- 29796606 TI - Shift work, chronotype and the risk of cardiometabolic risk factors. AB - Background: The relation between shift work and a large variety of cardiometabolic risk factors is unclear. Also, the role of chronotype is understudied. We examined relations between shift work and cardiometabolic risk factors, and explored these relations in different chronotypes. Methods: Cardiometabolic risk factors (anthropometry, blood pressure, lipids, diabetes, gamma-glutamyltransferase, C-reactive protein, uric acid and estimated glomerular filtration rate) were assessed among 1334 adults in 1987-91, with repeated measurements every 5 years. Using shift work history data collected in 2013-15, we identified shift work status 1 year prior to all six waves. Linear mixed models and logistic generalized estimating equations were used to estimate the longitudinal relations between shift work and risk factors 1 year later. Results: Shift work was not significantly related with cardiometabolic risk factors (P >= 0.05), except for overweight/body mass index. Shift workers had more often overweight (OR: 1.44, 95% CI 1.06-1.95) and a higher body mass index (BMI) (beta: 0.56 kg m-2, 95% CI 0.10-1.03) than day workers. A significant difference in BMI between day and shift workers was observed among evening chronotypes (beta: 0.97 kg m-2, 95% CI 0.21-1.73), but not among morning chronotypes (beta: 0.04 kg m-2, 95% CI -0.85 to 0.93). No differences by frequency of night shifts and duration of shift work were observed. Conclusion: Shift workers did not have an increased risk of cardiometabolic risk factors compared with day workers, but, in particular shift working evening chronotypes, had an increased risk of overweight. More research is needed to verify our results, and establish whether tailored interventions by chronotype are wanted. PMID- 29796608 TI - Use and application of 3D-organoid technology. AB - The capacity of the 3D-organoid cultures to resemble a near-physiological tissue organization and to mimic - to a certain degree - organ functionality, make organoids an excellent model for applications spanning from basic developmental/stem cell research to personalized medicine. Here, we review key findings achieved through organoid technology, and we discuss applications such as disease - and tumour modelling, correction of genetic mutations and understanding gene - and cell functions. Finally, we discuss future developments in the field. PMID- 29796607 TI - Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention. AB - Objective: to examine the associations of cardiovascular disease (CVD) and cardiovascular risk factors with frailty. Design: a cross-sectional study. Setting: the Irish Longitudinal Study on Ageing (TILDA). Participants: frailty measures were obtained on 5,618 participants and a subset of 4,330 participants with no prior history of CVD. Exposures for observational study: cardiovascular risk factors were combined in three composite CVD risk scores (Systematic Coronary Risk Evaluation [SCORE], Ideal Cardiovascular Health [ICH] and Cardiovascular Health Metrics [CHM]). Main outcome measures: a frailty index (40 items) was used to screen for frailty. Methods: the associations of CVD risk factors with frailty were examined using logistic regression. Results: overall, 16.4% of participants had frailty (7.6% at 50-59 years to 42.5% at 80+ years), and the prevalence was higher in those with versus those without prior CVD (43.0% vs. 10.7%). Among those without prior CVD, mean levels of CVD risk factors were closely correlated with higher frailty index scores. Combined CVD risk factors, assessed using SCORE, were linearly and positively associated with frailty. Compared to low-to-moderate SCOREs, the odds ratio (OR) (95% confidence interval, CI) of frailty for those with very high risk was 3.18 (2.38-4.25). Conversely, ICH was linearly and inversely associated with frailty, with an OR for optimal health of 0.29 (0.21-0.40) compared with inadequate health. Conclusions: the concordant positive associations of SCORE and inverse associations of ICH and CHM with frailty highlight the potential importance of optimum levels of CVD risk factors for prevention of disability in frail older people. PMID- 29796609 TI - Vitamin D deficiency is associated with mortality in maintenance dialysis: moving forward from epidemiology to clinical trials. PMID- 29796610 TI - Mad moves of the building blocks - nucleotide sugars find unexpected paths into cell walls. PMID- 29796611 TI - In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae. AB - Objectives: Increased antimicrobial resistance surveillance and new effective antimicrobials are crucial to maintain treatable gonorrhoea. We examined the in vitro activity of gepotidacin, a novel triazaacenaphthylene, and the effect of efflux pump inactivation on clinical Neisseria gonorrhoeae isolates and international reference strains (n = 252) and compared gepotidacin with antimicrobials currently or previously recommended for gonorrhoea treatment. Methods: MICs (mg/L) were determined by agar dilution (gepotidacin) or by Etest (seven other antimicrobials). The gyrA and parC genes were sequenced and the impact of inactivation of the MtrCDE, MacAB and NorM efflux pumps on gepotidacin MICs was examined. Results: Gepotidacin showed potent in vitro activity against all gonococcal isolates (n = 252; MIC <=4 mg/L). The modal MIC, MIC50, MIC90 and MIC range of gepotidacin were 0.5, 0.5, 1 and 0.032-4 mg/L, respectively. Inactivation of the MtrCDE efflux pump, but not MacAB or NorM, decreased the gepotidacin MICs for most strains. No significant cross-resistance between gepotidacin and any other antimicrobials, including the fluoroquinolone ciprofloxacin, was identified. However, the ParC D86N mutation (possibly together with additional antimicrobial resistance mutation), which is associated with fluoroquinolone resistance, was associated with increased gepotidacin MICs. Conclusions: Gepotidacin demonstrated high in vitro activity against gonococcal strains, indicating that gepotidacin could potentially be an effective option for gonorrhoea treatment, particularly in a dual antimicrobial therapy regimen and for patients with resistance or allergy to extended-spectrum cephalosporins. Nevertheless, elucidating in vitro and in vivo resistance emergence and mechanisms in detail, together with further gonorrhoea clinical studies, ideally also including chlamydia and Mycoplasma genitalium are essential. PMID- 29796612 TI - Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique. AB - BACKGROUND: The management of medically refractory epilepsy patients who are not surgical candidates has remained challenging. Closed loop-or responsive neurostimulation (RNS) is now an established therapy for the treatment of epilepsy with specific indications. The RNS(r) system (NeuroPace Inc, Mountainview, California) has recently been shown to be effective in reducing the seizure frequency of partial onset seizures. The electrode design consists of either intracerebral depth electrodes or subdural strip electrodes, and stereotaxis is typically used to guide placement into the EZ. Details on the operative techniques used to place these electrodes have been lacking. OBJECTIVE: To address the advantage of using a robotic-assisted technique to place depth electrodes for RNS(r) system placement compared to the typical frame-based or frameless stereotactic systems. METHODS: We retrospectively reviewed our single center, technical operative experience with RNS(r) system placement using robotic assistance from 2014 to 2016 via chart review. RESULTS: Twelve patients underwent RNS(r) system placement using robotic assistance. Mean operative time was 121 min for a median of 2 depth electrodes with mean deviation from intended target of ~3 mm in x, y, and z planes. Two patients developed wound infections, 1 of whom was reimplanted. Seizures were reduced by ~40% at 2 yr, similar to the results seen in the open label portion of the pivotal RNS trial. CONCLUSION: Robotic-assisted stereotaxis can be used to provide a stable and accurate stereotactic platform for insertion of intracerebral RNS electrodes, representing a safe, efficient and accurate procedure. PMID- 29796614 TI - Anxiety and depressive symptoms, and stress biomarkers in pregnant women after in vitro fertilization: a prospective cohort study. AB - STUDY QUESTION: Does in vitro fertilization (IVF) affect the course of anxiety and depressive symptoms as well as physiological stress from pregnancy to postpartum period? SUMMARY ANSWER: IVF mothers have more anxiety symptoms and higher stress biomarker levels but fewer depression symptoms than natural conception mothers at the third trimester of pregnancy, but these differences are negligible during postpartum period. WHAT IS KNOWN ALREADY: Cross-sectional studies have found an association between IVF and high stress levels during the prenatal period. There is, however, no follow-up study about the IVF effect on the mental health status from pregnancy to postpartum, adopting simultaneous measurement of self-reported symptoms and stress biomarkers. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study. A total of 243 eligible women were recruited during the third trimester of pregnancy (60 women after successful IVF and 183 who conceived naturally). The recruitment was performed during a 12-month period, and the follow-up was carried out until 3 months after delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in the Division of Obstetrics in a regional referral center. The State scale of the State-Trait Anxiety Inventory (STAI-S) and the Beck Depression Inventory-Sort Form (BDI/SF) were used as anxiety and depression indicators, respectively; salivary cortisol and alpha-amylase levels as stress biomarkers. Anxiety, depression and stress biomarkers were measured at the third trimester of pregnancy (T1), at 48 h after birth (T2) and at 3 months after birth (T3). Associations with IVF were assessed using ordinal mixed models for anxiety and depressive symptoms and linear quantile models for stress biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: Relative to natural conception mothers, IVF mothers had higher STAI-S scores at T1 (P = 0.016, odds ratio (OR) = 2.46), and this difference remained steady from T1 to T2 (P = 0.37, OR = 0.70) and from T2 to T3 (P = 0.36, OR = 0.69). In the case of depressive symptoms, the IVF group obtained lower BDI/SF scores at T1 (P < 0.001, OR = 0.192). This difference was apparently reduced from T1 to T2 (P = 0.072, OR = 2.21) and remained constant from T2 to T3 (P = 0.107, OR = 2.09). It is important to note that whereas the mean BDI/SF score was not clinically significant for any group (it was lower than the cut-off 4), the mean STAI-S score of the IVF group at T1 was so (it was higher than the cut-off 19). As for stress biomarkers, IVF mothers had higher cortisol levels at T1 (P = 0.043, Deltalog(cortisol) = 0.88) compared to natural conceptions. From T1 to T2 cortisol levels of both groups increased at the relatively same rate (P = 0.81, Deltalog(cortisol) = -0.16). However, the progressions tended to be different from T2 to T3, with IVF mothers exhibiting a sharp decrease in cortisol levels (P = 0.059, Deltalog(cortisol) = -0.94), while natural conceptions value remained steady. In the case of alpha-amylase, there were no statistically significant differences between both groups at T1 (P = 0.7, Deltalog(alpha-amylase) = -0.095). On the contrary, while IVF mothers showed sustained alpha-amylase levels across the time, the progression was different in the natural conception group, who showed a decrease in alpha-amylase levels from T1 to T2 (P = 0.049, Deltalog(alpha-amylase) = 0.596) and a non-significant increase from T2 to T3 (P = 0.53, Deltalog(alpha-amylase) = -0.283). LIMITATIONS REASON FOR CAUTION: Since this follow-up study has been carried out from the third trimester of pregnancy, the findings cannot be generalized to extremely preterm births. WIDER IMPLICATIONS OF THE FINDINGS: IVF women may have lower depressive symptoms for being pregnant. However, due to the potential pregnancy complications associated with IVF, they may have higher physiological stress and clinically significant anxiety at the third trimester of pregnancy but not during postpartum. Taking into account that both prenatal high maternal cortisol levels and prenatal clinically significant anxiety increase the risk of disturbance in the fetal neurodevelopment, psychological therapy should be extended during pregnancy in IVF women. STUDY FUNDING/COMPETING INTEREST(S): MV funded by FIS PI17/0131 grant from the Instituto de Salud Carlos III (ISCIII) and RETICS funded by the PN 2018-2011, and the European Regional Development Fund, reference RD16/0022/0001; AG-B funded by a 'Juan Rodes' Grant (JR17/00003) from the ISCIII. CC-P funded by a 'Miguel Servet I' Grant (CP16/00082) from the ISCIII. Authors declare no competing interests. PMID- 29796613 TI - Coal and oil power plant retirements in California associated with reduced preterm birth among populations nearby. AB - Coal and oil power plant retirements reduce air pollution nearby, but few studies have leveraged these natural experiments for public health research. We used California Department of Public Health birth records and Energy Information Administration data from 2001-2011 to evaluate the relationship between 8 coal and oil power plant retirements and nearby preterm births ( < 37 weeks gestational age). We conducted a difference-in-differences analysis using adjusted linear mixed models that included 57,005 births-6.5% of which were preterm-to compare the probability of preterm birth before and after power plant retirement among mothers residing within 0-5 km and 5-10 km of the 8 power plants. We found that power plant retirements were associated with a decrease in the proportion of preterm birth within 5 km (-0.019, 95% CI: -0.031, -0.008) and 5-10 km (-0.015, 95% CI: -0.024, -0.007) controlling for secular trends with mothers living 10-20 km away. For the 0-5 km area, this corresponds to a reduction in preterm birth from 7.0% to 5.1%. Subgroup analyses indicated a potentially larger association among non-Hispanic Black and Asian mothers compared to non-Hispanic White and Hispanic mothers and no differences in educational attainment. Future coal and oil power plant retirements may reduce preterm birth among nearby populations. PMID- 29796616 TI - Twenty-first Century Cures Act and Antimicrobial Susceptibility Testing: Clinical Implications in the Era of Multidrug Resistance. AB - Clinical laboratories act at the frontline of identification of infections caused by multidrug-resistant organisms, and yet the tools they apply are often woefully out of date. Incomplete adoption of current testing standards, updated breakpoints, and tests for new drugs across laboratories has been exacerbated by lack of coordination between standards development organizations (SDOs), pharmaceutical companies, susceptibility test manufacturers, and the US Food and Drug Administration. The 21st Century Cures Act includes provisions to enable alignment between these groups by (1) allowing recognition of breakpoints set by qualified SDOs; (2) publicly posting recognized breakpoints; and (3) reviewing breakpoints for necessary updates, every 6 months. Combined, these provisions will ensure more rapid recognition of current breakpoints, improving detection and management of resistant infections. Although several limitations remain, this will ultimately allow susceptibility test manufacturers to more readily update to current breakpoints. PMID- 29796615 TI - Oncolytic virotherapy in glioblastoma patients induces a tumor macrophage phenotypic shift leading to an altered glioblastoma microenvironment. AB - Background: Immunosuppressive protumoral M2 macrophages are important in pathogenesis, progression, and therapy resistance in glioblastoma (GBM) and provide a target for therapy. Recently oncolytic virotherapy in murine models was shown to change these M2 macrophages toward the pro-inflammatory and antitumoral M1 phenotype. Here we study the effects of the oncolytic virotherapy Delta24-RGD in humans, using both in vitro models and patient material. Methods: Human monocyte-derived macrophages were co-cultured with Delta24-RGD-infected primary glioma stem-like cells (GSCs) and were analyzed for their immunophenotype, cytokine expression, and secretion profiles. Cerebrospinal fluid (CSF) from 18 Delta24-RGD-treated patients was analyzed for inflammatory cytokine levels, and the effects of these CSF samples on macrophage phenotype in vitro were determined. In addition, tumor macrophages in resected material from a Delta24 RGD-treated GBM patient were compared with 5 control GBM patient samples by flow cytometry. Results: Human monocyte-derived M2 macrophages co-cultured with Delta24-RGD-infected GSCs shifted toward an M1-immunophenotype, coinciding with pro-inflammatory gene expression and cytokine production. This phenotypic switch was induced by the concerted effects of a change in tumor-produced soluble factors and the presence of viral particles. CSF samples from Delta24-RGD-treated GBM patients revealed cytokine levels indicative of a pro-inflammatory microenvironment. Furthermore, tumoral macrophages in a Delta24-RGD-treated patient showed significantly greater M1 characteristics than in control GBM tissue. Conclusion: Together these in vitro and patient studies demonstrate that local Delta24-RGD therapy may provide a therapeutic tool to promote a prolonged shift in the protumoral M2 macrophages toward M1 in human GBM, inducing a pro inflammatory and potentially tumor-detrimental microenvironment. PMID- 29796617 TI - DNA methylation alterations-potential cause of endometriosis pathogenesis or a reflection of tissue heterogeneity? AB - Alterations in the DNA methylation pattern of endometriotic lesions and endometrium of endometriosis patients have been proposed as one potential factor accompanying the endometriosis development. Although many differentially methylated genes have been associated with the pathogenesis of this disease, the overlap between the results of different studies has remained small. Among other potential confounders, the impact of tissue heterogeneity on the outcome of DNA methylation studies should be considered, as tissues are mixtures of different cell types with their own specific DNA methylation signatures. This review focuses on the results of DNA methylation studies in endometriosis from the cellular heterogeneity perspective. We consider both the studies using highly heterogeneous whole-lesion biopsies and endometrial tissue, as well as pure cell fractions isolated from lesions and endometrium to understand the potential impact of the cellular composition to the results of endometriosis DNA methylation studies. Also, future perspectives on how to diminish the impact of tissue heterogeneity in similar studies are provided. PMID- 29796618 TI - MiR-7 Mediates the Zearalenone Signaling Pathway Regulating FSH Synthesis and Secretion by Targeting FOS in Female Pigs. AB - Zearalenone (ZEA) acts as an environmental endocrine disruptor (EED) to cause health detriments. miRNAs were reported to influence the synthesis and secretion of pituitary hormones. However, the interactions between ZEA and miRNAs and related mechanisms remain unclear. The aims of this study were to determine whether and how miR-7 affects animal reproduction by its interactions with ZEA in the pig pituitary, which is sensitive to ZEA and has been used as an important animal model in medical research. Expressions of miRNA were detected by real-time PCR, in situ hybridization, and immunohistochemistry. The effects of ZEA, miR-7, and their interactions in the pituitary gland were identified by using an ovariectomized pig model, transfecting miR-7 mimics and inhibitor, radioimmunoassay, luciferase reporter assay, and Western blotting. The ZEA dosage was 7.5 mg/kg body weight in vivo and 1 MUM in vitro. Our results demonstrate miR 7 acts to regulate gonadotropin synthesis and secretion. Furthermore, we found that ZEA leads to reproductive defects by enhancing miR-7 expression, which subsequently inhibits FSH synthesis and secretion. In vitro and in vivo experiments revealed that the effects of ZEA rely on G protein-coupled estrogen receptor 1, and miR-7 functions by mediating ZEA signaling pathway and targeting the Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (FOS) gene. These findings show that miRNAs are key intrinsic factors regulating pituitary gonadotropins by mediating EED signaling in pituitary glands, and the actions of miRNAs and EEDs should be seriously considered in related studies about medical practice and animal production. PMID- 29796619 TI - Slow luminescence kinetics of semi-synthetic aequorin: expression, purification and structure determination of cf3-aequorin. AB - cf3-Aequorin is one of the semi-synthetic aequorins that was produced by replacing 2-peroxycoelenterazine (CTZ-OOH) in native aequorin with a 2 peroxycoelenterazine analog, and it was prepared using the C2-modified trifluoromethyl analog of coelenterazine (cf3-CTZ) and the histidine-tagged apoaequorin expressed in Escherichia coli cells. The purified cf3-aequorin showed a slow luminescence pattern with half-decay time of maximum intensities of luminescence of 5.0 s. This is much longer than that of 0.9 s for native aequorin, and its luminescence capacity was estimated to be 72.8% of that of native aequorin. The crystal structure of cf3-aequorin was determined at 2.15 A resolution. The light source of 2-peroxytrifluoromethylcoelenterazine (cf3-CTZ OOH) was stabilized by the hydrogen-bonding interactions at the C2-peroxy moiety and the p-hydroxy moiety at the C6-phenyl group. In native aequorin, three water molecules contribute to stabilizing CTZ-OOH through hydrogen bonds. However, cf3 aequorin only contained one water molecule, and the trifluoromethyl moiety at the C2-benzyl group of cf3-CTZ-OOH interacted with the protein by van der Waals interactions. The slow luminescence kinetics of cf3-aequorin could be explained by slow conformational changes due to the bulkiness of the trifluoromethyl group, which might hinder the smooth cleavage of hydrogen bonds at the C2-peroxy moiety after the binding of Ca2+ to cf3-aequorin. PMID- 29796620 TI - Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1. AB - Background: Inflammatory bowel disease (IBD)-associated dysbiosis is characterized by a loss of Faecalibacterium prausnitzii, whose supernatant exerts an anti-inflammatory effect. However, the anti-inflammatory substances in F. prausnitzii supernatant and the mechanism in ameliorating colitis in IBD have not yet been fully investigated. Methods: Experimental colitis models were induced and evaluated by clinical examination and histopathology. Levels of cytokines and ratio of T cells were detected by enzyme-linked immunosorbent assay and flow cytometry analysis, respectively. F. prausnitzii supernatant was separated by macroporous resins. After extraction, the substances in supernatant were identified by gas chromatography-mass spectrometer. T-cell differentiation assay was conducted in vitro. Changes in signaling pathways were examined by immunoblot, immunohistochemistry, and immunofluorescent staining. Results: We found that the supernatant of F. prausnitzii could regulate T helper 17 cell (Th17)/regulatory T cell (Treg) differentiation. Then, we identified butyrate produced by F. prausnitzii that played the anti-inflammatory effects by inhibiting interleukin (IL)-6/signal transducer and the activator of transcription 3 (STAT3)/IL-17 pathway and promoting forkhead box protein P3 (Foxp3). Finally, we demonstrated that the target of butyrate was histone deacetylase 1 (HDAC1). Conclusions: It is butyrate, instead of other substances produced by F. prausnitzii, that maintains Th17/Treg balance and exerts significant anti-inflammatory effects in colorectal colitis rodents, by inhibiting HDAC1 to promote Foxp3 and block the IL-6/STAT3/IL-17 downstream pathway. F. prausnitzii could be an option for further investigation for IBD treatment. Targeting the butyrate-HDAC1-T-cell axis offers an effective novel approach in the treatment of inflammatory disease. PMID- 29796621 TI - Premature Expression of FOXO1 in Developing Mouse Pituitary Results in Anterior Lobe Hypoplasia. AB - The process by which the somatotrope lineage emerges in the developing pituitary is regulated by the activity of specific signaling and transcription factors expressed during development. We set out to understand the contribution of FOXO1 to that process by using a mouse model in which FOXO1 is prematurely expressed in the pituitary primordium. Expression of FOXO1 in the oral ectoderm as early as embryonic day (e)9.5 resulted in pituitary gland hypoplasia and reduced expression of anterior lobe hormone transcripts at e18.5. Of note, the relative numbers of somatotropes and thyrotropes were also decreased at e18.5. LHX3 and PITX2, markers of pituitary identity, were present in a reduced number of cells during the formation of the Rathke pouch. Thus, premature expression of FOXO1 may affect adoption of pituitary identity during differentiation. Our results demonstrate that the timing of FOXO1 activation affects its role in pituitary gland organogenesis and somatotrope differentiation. PMID- 29796623 TI - The Screening Illustrator: separating the effects of lead-time and overdiagnosis in mammography screening. AB - Background: Mammography screening increases incidence because cancers are detected earlier in time and because of overdiagnosis. We developed an Excel based model to visualize the expected increase from lead-time amplified by increasing background incidence. Subsequently, we added overdiagnosis to the model. Methods: We constructed two hypothetical populations of women aged 50-79 in 5-year age and calendar groups: one with screening for women aged 50-69 and one without. The user enters information on population at risk, number of breast cancers, trends in background incidence, average length of lead-time and, optionally, overdiagnosis. The model computes incidence rate ratios (IRRs) comparing incidence changes with screening to changes without in open and closed cohorts. Results: We entered information from Norway from 1990 to 1994, the period preceding the gradual introduction of a national mammography screening programme. As expected, the Screening Illustrator showed prevalence peaks and compensatory drops. Only the closed cohort approach remained unaffected by increasing background incidence. The model showed a 20% sustained increase in incidence (IRR: 1.20) from lead-time and increasing background incidence in the open cohort approach for women aged 50-69. However, real life Norwegian data show a corresponding 38% increase. For the model to achieve the observed incidence, 10 14% overdiagnosis had to be added. Conclusion: The observed breast cancer incidence increase in Norway after screening implementation could not be obtained from an average lead-time of 2.5 years and empirical background incidence trends, but had to incorporate overdiagnosis. PMID- 29796622 TI - Gestational Age and Maternal Serum 25-hydroxyvitamin D Concentration Interact to Affect the 24,25-dihydroxyvitamin D Concentration in Pregnant Adolescents. AB - Background: Interpretation of serum vitamin D biomarkers across pregnancy is complex due to limited understanding of pregnancy adaptations in vitamin D metabolism. During pregnancy, both gestational age and serum 25-hydroxyvitamin D [25(OH)D] concentrations may influence the concentrations of 1,25 dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and parathyroid hormone (PTH). Objective: We aimed to identify predictors of change in serum 25(OH)D across gestation in pregnant adolescents and to assess the contribution made by cholecalciferol (vitamin D3) supplementation. We sought to determine whether gestational age and 25(OH)D concentration interacted to affect serum 1,25(OH)2D, 24,25(OH)2D, or PTH. Methods: Pregnant adolescents (n = 78, 59% African American, mean +/- SD age: 17 +/- 1 y) living in Rochester, NY (latitude 43 degrees N) were supplemented with 200 IU or 2000 IU vitamin D3/d and allowed to continue their daily prenatal supplement that contained 400 IU vitamin D3. Serum was collected at study entry (18 +/- 5 wk of gestation), halfway through study participation, and at delivery (40 +/- 2 wk). Serum concentrations of the biochemical markers were modeled with linear mixed-effects regression models. Results: Vitamin D3 supplement intake and season of delivery determined change in 25(OH)D across pregnancy. Fall-winter delivery was associated with a decline in 25(OH)D unless vitamin D3 supplement intake was >872 IU/d. The interaction of gestational age and 25(OH)D affected 24,25(OH)2D concentrations. For a given 25(OH)D concentration, model-predicted serum 24,25(OH)2D increased across gestation except when 25(OH)D was <13 ng/mL. Below this threshold, 24,25(OH)2D was predicted to decline over time. Mean serum 1,25(OH)2D was elevated (>100 pg/mL) throughout the study. Conclusion: Our results suggest that when maternal serum 25(OH)D was low, its catabolism into 24,25(OH)2D decreased or remained stable as pregnancy progressed in order to maintain persistently elevated serum 1,25(OH)2D. Furthermore, in adolescents living at latitude 43 degrees N, standard prenatal supplementation did not prevent a seasonal decline in 25(OH)D during pregnancy. This study was registered at clinicaltrials.gov as NCT01815047. PMID- 29796625 TI - Amino Acid- and Insulin-Induced Activation of mTORC1 in Neonatal Piglet Skeletal Muscle Involves Sestin2-GATOR2, Rag A/C-mTOR, and RHEB-mTOR Complex Formation. AB - Background: Feeding stimulates protein synthesis in skeletal muscle of neonates and this response is regulated through activation of mechanistic target of rapamycin complex 1 (mTORC1). The identity of signaling components that regulate mTORC1 activation in neonatal muscle has not been fully elucidated. Objective: We investigated the independent effects of the rise in amino acids (AAs) and insulin after a meal on the abundance and activation of potential regulators of mTORC1 in muscle and whether the responses are modified by development. Methods: Overnight fasted 6- and 26-d-old pigs were infused for 2 h with saline (control group) or with a balanced AA mixture (AA group) or insulin (INS group) to achieve fed levels while insulin or AAs, respectively, and glucose were maintained at fasting levels. Muscles were analyzed for potential mTORC1 regulatory mechanisms and results were analyzed by 2-factor ANOVA followed by Tukey's post hoc test. Results: The abundances of DEP domain-containing mTOR-interacting protein (DEPTOR), growth factor receptor bound protein 10 (GRB10), and regulated in development and DNA damage response 2 (REDD2) were lower (65%, 73%, and 53%, respectively; P < 0.05) and late endosomal/lysosomal adaptor, MAPK and mTOR activator 1/2 (LAMTOR1/2), vacuolar H+-ATPase (V-ATPase), and Sestrin2 were higher (94%, 141%, 145%, and 127%, respectively; P < 0.05) in 6- than in 26-d-old pigs. Both AA and INS groups increased phosphorylation of GRB10 (P < 0.05) compared with control in 26- but not in 6-d-old pigs. Formation of Ras-related GTP-binding protein A (RagA)-mTOR, RagC-mTOR, and Ras homolog enriched in brain (RHEB)-mTOR complexes was increased (P < 0.05) and Sestrin2-GTPase activating protein activity towards Rags 2 (GATOR2) complex was decreased (P < 0.05) by both AA and INS groups and these responses were greater (P < 0.05) in 6- than in 26-d old pigs. Conclusion: The results suggest that formation of RagA-mTOR, RagC-mTOR, RHEB-mTOR, and Sestrin2-GATOR2 complexes may be involved in the AA- and INS induced activation of mTORC1 in skeletal muscle of neonates after a meal and that enhanced activation of the mTORC1 signaling pathway in neonatal muscle is in part due to regulation by DEPTOR, GRB10, REDD2, LAMTOR1/2, V-ATPase, and Sestrin2. PMID- 29796624 TI - Effect of cumulative exposure to corticosteroid and DMARD on radiographic progression in rheumatoid arthritis: results from the ESPOIR cohort. AB - Objectives: Several authors have tried to predict the risk of radiographic progression in RA according to baseline characteristics, considering exposure to treatment only as a binary variable (Treated: Yes/No). This study aims to model the risk of 5-year radiographic progression taking into account both baseline characteristics and the cumulative time-varying exposure to corticosteroids or DMARDs. Methods: The study population consisted of 403 patients of the Etude et Suivi des Polyarthrites Indifferenciees Recentes cohort meeting the 1987 ACR or 2010 ACR/EULAR criteria for RA at inclusion and having complete radiographic data at baseline and 5 years. Radiographic progression was defined at 5 years as a significant increase of the Sharp/van der Heidje score (smallest detectable difference ?5). The best logistic regression model was selected from the following: model including only clinico-biological baseline characteristics; model considering baseline characteristics and treatments as binary variables; and model considering baseline characteristics and treatments as weighted cumulative exposure variables. Results: Radiographic progression occurred in 143 (35.5%) patients. The best model combined anti-citrullinated peptide antibody positivity, ESR, swollen joint count >14 and erosion score at baseline, as well as corticosteroids, MTX/LEF (MTX or LEF) and biologic DMARDs (bDMARDs) as weighted cumulative exposure variables. Recent cumulative exposure to high doses of corticosteroids (? 3months) was significantly associated with the risk of 5 year radiographic progression and a significant protective association was highlighted for a 36-month exposure to bDMARDs. Conclusion: Corticosteroids and bDMARDs play an important role in radiographic progression. Accounting for treatment class and intensity of exposure is a major concern in predictive models of radiographic progression in RA patients. PMID- 29796626 TI - Letter: Passing the Needle and Pulling the Thread. PMID- 29796627 TI - Moving toward Objective Biomarkers of Dietary Intake. PMID- 29796628 TI - The power of preterm birth to motivate a cleaner environment. AB - This commentary reflects on a natural experiment reported by Casey and colleagues that tested the association between living near a coal or oil power plant and preterm birth. They found that retiring power plants resulted in a significant reduction in preterm birth with larger effects observed for late preterm birth and among Non-Hispanic Black mothers and infants. Natural experiments, in particular the Utah Valley steel mill closure, have played a prominent role in the evidence-base for air pollution regulation due to their demonstrated impact on cardio-pulmonary effects in adults. Reproductive health, including infant mortality and preterm birth associated with poor air quality, have generally received less attention. Even small reductions in preterm birth can have a large population health impact, both in terms of preventing mortality in the short-term but also preventing lifelong disability among affected infants. PMID- 29796629 TI - OCCUPATIONAL DOSES FOR THE FIRST AND SECOND OPERATORS IN LEBANESE INTERVENTIONAL CARDIOLOGY SUITES. AB - The study monitored occupational dose for 12 interventional cardiologists (first operators) and 10 technicians (second operators), from 10 different Lebanese hospitals performing coronary angiography and precutaneous coronary interventions exclusively on adult patients. Each individual wore dosemeters under and over the lead apron at chest and collar level, respectively, on the wrist and next to the left eye. The total follow-up period for each first/second operator varied between two to six bimonthly monitoring periods. For the first operator, the mean (range) effective, hand and eye lens doses were of 6 (1-41), 112 (10-356) and 15 (5-47) MUSv/procedure, respectively. These were of 2.3 (0.1-8), 16 (2-109) and 7 (2-14) MUSv/procedure for the second operator. Extrapolated annual eye lens doses revealed that both first and second operators may exceed 3/10th of the annual eye lens dose permissible limit thus supporting the need for dedicated eye lens monitoring. PMID- 29796630 TI - Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2. AB - Blood dendritic cell antigen 2 (BDCA-2) is a C-type lectin found on the surface of plasmacytoid dendritic cells. It functions as a glycan-binding receptor that downregulates the production of type I interferons and thus plays a role in oligosaccharide-mediated immunomodulation. The carbohydrate recognition domain in BDCA-2 binds selectively to galactose-terminated bi-antennary glycans. Because the plasmacytoid dendritic cells function in a plasma environment rich in glycoproteins, experiments have been undertaken to identify endogenous ligands for blood dendritic cell antigen 2. A combination of blotting, affinity chromatography and proteomic analysis reveals that serum glycoprotein ligands for BDCA-2 include IgG, IgA and IgM. Compared to binding of IgG, which was previously described, IgA and IgM bind with higher affinity. The association constants for the different subclasses of immunoglobulins are below and roughly proportional to the serum concentrations of these glycoprotein ligands. Binding to the other main serum glycoprotein ligand, alpha2-macroglobulin, is independent of whether this protease inhibitor is activated. Binding to all of these glycoprotein ligands is mediated predominantly by bi-antennary glycans in which each branch bears a terminal galactose residue. The different affinities of the glycoprotein ligands reflect the different numbers of these galactose-terminated glycans and their degree of exposure on the native glycoproteins. The results suggest that normal serum levels of immunoglobulins could downmodulate interferon stimulation of further antibody production. PMID- 29796631 TI - Chromosomal mosaicism in human blastocysts: the ultimate challenge of preimplantation genetic testing? AB - STUDY QUESTION: To what extent does a trophectoderm (TE) biopsy reliably reflect the chromosomal constitution of the inner cell mass (ICM) in human blastocysts? SUMMARY ANSWER: Concordance between TE and ICM was established in 62.1% of the embryos analysed. WHAT IS KNOWN ALREADY: Next generation sequencing (NGS) platforms have recently been optimised for preimplantation genetic testing for aneuploidies (PGT-A). However, higher sensitivity has led to an increase in reports of chromosomal mosaicism within a single TE biopsy. This has raised substantial controversy surrounding the prevalence of mosaicism in human blastocysts and the clinical implications of heterogeneity between the TE and ICM. STUDY DESIGN, SIZE, DURATION: To define the distribution and rate of mosaicism in human blastocysts, we assessed chromosomal profiles of the ICM and multiple TE portions obtained from the same embryo. We evaluated donated embryos with an unknown chromosomal profile (n = 34), as well as PGT-A blastocysts, previously diagnosed as abnormal or mosaic (n = 24). Our intra-embryo comparison included a total of 232 samples, obtained from 58 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: Four embryo samples, including the ICM and three distinct TE portions, were acquired from good quality blastocysts by micromanipulation. Whole genome amplification (WGA), followed by NGS was performed on all embryo segments. Profiles were compared between samples from the same embryo, while the results from pretested blastocysts were further correlated to the original report. The embryos investigated in our untested group were obtained from good prognosis patients (n = 25), with maternal age ranging from 23 to 39 years. For the pretested embryo group, maternal age ranged from 23 to 40 years (n = 18). MAIN RESULTS AND THE ROLE OF CHANCE: We uncover chromosomal mosaicism, involving both numerical and structural aberrations, in up to 37.9% of the blastocysts analysed. Within the untested group, the overall concordance between the ICM and all TE portions was 55.9%. A normal ICM was detected in 20.6% of blastocysts for which at least one TE portion showed a chromosomal aberration. Conversely, 17.6% of embryos presented with mosaic or uniform abnormalities within the ICM, while showing normal or mosaic TE profiles. For the pretested blastocysts, the overall concordance between the ICM and all TE samples was 70.8%. However, 50% of embryos previously diagnosed with mosaicism did not confirm the original diagnosis. Notably, 31.3% of embryos with a mosaic aberration reported in the original TE biopsy, revealed a euploid profile in the ICM and all three TE samples. Taken together, concordance between the ICM and all TE portions was established in 62.1% of blastocysts, across both embryo groups. Finally, we could not observe a significant effect of age on embryo mosaicism (P = 0.101 untested group; P = 0.7309 pretested group). Similarly, ICM and TE quality were not found to affect the occurrence of chromosomal mosaicism (P = 0.718 and P = 0.462 untested group; P = 1.000 and P = 0.2885 pretested group). LARGE SCALE DATA: All data that support the findings of this study are available online in Vivar (http://cmgg.be/vivar) upon request. LIMITATIONS, REASONS FOR CAUTION: Evaluating biological variation in some instances remains challenging. The technological limitations of sampling mitotic errors that lead to mosaicism, as well as WGA artefacts, warrant careful interpretation. WIDER IMPLICATIONS OF THE FINDINGS: Our results highlight the complex nature of genetic (in)stability during early ontogenesis and indicate that blastocysts harbour a higher rate of chromosomal mosaicism than may have been anticipated. Moreover, our findings reveal an overall high diagnostic sensitivity and relatively low specificity in the context of PGT-A. This suggests that a considerable proportion of embryos are potentially being classified as clinically unsuitable. Ultimately, more precise quantification will benefit the clinical management of embryo mosaicism. STUDY FUNDING/COMPETING INTEREST(S): M.P. is supported by the Special Research Fund, Bijzonder Onderzoeksfonds (BOF01D08114). J.T. and L.D. are supported by the agency for innovation through science (131673, 141441). B.H. and this research are supported by the Special Research Fund, Bijzonder Onderzoeksfonds (BOF15/GOA/011). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 29796633 TI - Pitfalls of linear regression for estimating slopes over time and how to avoid them by using linear mixed-effects models. AB - Clinical epidemiological studies often focus on investigating the underlying causes of disease. For instance, a nephrologist may be interested in the association between blood pressure and the development of chronic kidney disease (CKD). However, instead of focusing on the mere occurrence of CKD, the decline of kidney function over time might be the outcome of interest. For examining this kidney function trajectory, patients are typically followed over time with their kidney function estimated at several time points. During follow-up, some patients may drop out earlier than others and for different reasons. Furthermore, some patients may have greater kidney function at study entry or faster kidney function decline than others. Also, a substantial heterogeneity may exist in the number of kidney function estimates available for each patient. This heterogeneity with respect to kidney function, dropout and number of kidney function estimates is important to take into account when estimating kidney function trajectories. In general, two methods are used in the literature to estimate kidney function trajectories over time: linear regression to estimate individual slopes and the linear mixed-effects model (LMM), i.e. repeated measures analysis. Importantly, the linear regression method does not properly take into account the above-mentioned heterogeneity, whereas the LMM is able to retain all information and variability in the data. However, the underlying concepts, use and interpretation of LMMs are not always straightforward. Therefore we illustrate this using a clinical example and offer a framework of how to model and interpret the LMM. PMID- 29796632 TI - Feasibility of a culturally adapted positive psychological intervention for Hispanics/Latinos with elevated risk for cardiovascular disease. AB - Although increasing emotional well-being has been proposed as a potential pathway to drive cardiac health, emotional well-being interventions for people with cardiac risk are underdeveloped, particularly among Hispanic/Latino adults. Our objective was to pilot a well-being intervention drawing on positive psychology concepts to determine feasibility and acceptability in Hispanics/Latinos at risk for cardiovascular disease (CVD). We developed a Spanish-language positive psychological intervention, with cultural tailoring informed by formative qualitative work, to promote emotional well-being and its antecedents in Hispanics/Latinos. Hispanic/Latino adults (n = 19) self-reporting two or more CVD risk factors were enrolled in our single-arm 8-week pilot trial. The group intervention consisted of 8 weekly 90-min sessions delivered by a bilingual licensed clinical social worker. Mean age was 54.1 years, 68.8% were female, and 50% had <=eighth-grade education. Eleven of 19 Hispanic/Latino adults completed the 8-week program for a 57.89% retention rate, with a majority of factors leading to dropout unrelated to program content or mode of delivery. Most participants felt satisfied overall with each session (97.1%). Largest increases relative to baseline after receiving the intervention were found in engagement in happiness-inducing behaviors (e.g., meditation), emotional vitality, and subjective happiness using metrics of reliable change and effect sizes. This single-arm trial documented adequate feasibility and acceptability, although strategies to increase retention are warranted. Future studies should test our intervention using a randomized trial design with a larger sample size and inclusion of biomarkers (e.g., C-reactive protein) to document impact of our intervention on cardiac-related health. PMID- 29796634 TI - LncRNA co-expression Network Analysis Reveals Novel Biomarkers for Pancreatic Cancer. AB - High mortality and low survival rates for pancreatic ductal adenocarcinoma (PDAC) mainly result from the delay in diagnosis and treatment. Therefore there is an urgent need to identify early PDAC biomarkers and new therapeutic targets. In this study, we applied a commonly used systems biology approach, the weighted gene co-expression network analysis (WGCNA), on lncRNA expression data. Eleven lncRNAs, namely A2M-AS1, DLEU2, LINC01133, LINC00675, MIR155HG, SLC25A25-AS1, LINC01857, LOC642852 (LINC00205), ITGB2-AS1, TSPOAP1-AS1 and PSMB8-AS1 have been identified and validated on an independent PDAC expression dataset. Furthermore, we characterised them by functional and pathway enrichment analysis and identified which lncRNAs showed differential expression, differential promoter methylation levels and copy number alterations between normal and PDAC samples. Finally, we also performed a survival analysis and identified A2M-AS1, LINC01133, LINC00205 and TSPOAP1-AS1 as prognostic biomarkers for PDAC. Interestingly, although only a few cancer-associated lncRNAs have been functionally characterized, LINC00675 and LINC01133 lncRNAs have been already demonstrated to be involved in PDAC development and progression. Therefore, our results provide new potential diagnostic/prognostic biomarkers and therapeutic targets for PDAC that deserve to be further investigated. Moreover, these lncRNAs may improve the understanding about molecular pathogenesis of PDAC. PMID- 29796635 TI - The ERA-EDTA today and tomorrow: a progress document by the ERA-EDTA Council. AB - Scientific societies are increasingly seen as central to the advancement of information sharing and collaboration among scientists and clinical investigators for the progress of medical research and the promotion of education, professional competence, integrity and quality studies. To more effectively serve the practicing nephrologists and investigators dedicated to renal science, the Council of the European Renal Association and European Dialysis and Transplantation Association (ERA-EDTA) reorganized and integrated the various activities of the society into two branches, the Clinical Nephrology Governance branch and the Renal Science branch. New affordable initiatives to promote research, education and professional development and to advocate for the recognition of chronic kidney disease as a major public health issue at the European level will be put in place and/or potentiated in the new organizational frame. Educational initiatives will be espoused to Continuous Professional Development and, starting from 2019, 14 Education & Continuous Professional Development courses will be held covering the full range of knowledge areas of modern nephrology. Consolidation and development is the short- and medium-term mantra of the ERA-EDTA. The society has a rich portfolio of successful activities and brilliant, creative scientists among its members. Integrating the various activities of the ERA-EDTA and treasuring the expertise and wisdom of its most accomplished members will facilitate collaborative research, education and its public impact at large. PMID- 29796637 TI - Comparisons of aortic remodelling and outcomes after endovascular repair of acute and chronic complicated Type B aortic dissections. AB - OBJECTIVES: Patients with acute (ACTBAD) or chronic complicated Type B aortic dissection (CCTBAD) undergoing thoracic endovascular aortic repair (TEVAR) remain at high risk for late aorta-related events. Few data exist on the comparison of aortic remodelling and outcomes after TEVAR between both groups. METHODS: Forty nine patients of TEVAR for CCTBAD (n = 26) and ACTBAD (n = 23) were retrospectively reviewed at our centre. RESULTS: The overall 30-day mortality was 4%. Cumulative freedom from all-cause mortality (ACTBAD: 77.6%, CCTBAD: 68.8%; P = 0.76), aneurysmal-related mortality (ACTBAD: 88.2%, CCTBAD: 95.0%; P = 0.63) and the 3-year reintervention rate (ACTBAD: 92.3%, CCTBAD: 95.6%; P = 0.94) were the same in both groups. Aortic remodelling was significant (P < 0.001) above the coeliac level after TEVAR. Thirty-five (75.5%) patients still experienced false lumen flow in the abdominal aorta below the coeliac artery (ACTBAD: 16, CCTBAD: 19, P = 0.10). No difference was found in aortic remodelling between the ACTBAD and CCTBAD groups, and the length of endograft coverage had no impact on the aortic remodelling. CONCLUSIONS: The early and 3-year follow-up in our study showed that endovascular repair for both ACTBAD and CCTBAD was safe and effective. Aortic remodelling was favourable above the coeliac artery after TEVAR, and no difference was found between ACTBAD and CCTBAD. The length of endograft coverage had no impact on aortic remodelling. The low rate of false lumen thrombosis in the abdominal aorta warranted continuous imaging surveillance. PMID- 29796638 TI - In Reply: Passing the Needle and Pulling the Thread. PMID- 29796636 TI - Rheumatoid arthritis and excess mortality: down but not out. A primary care cohort study using data from Clinical Practice Research Datalink. AB - Objectives: To examine temporal trends in all-cause and cause-specific mortality in RA. Methods: Data from the Clinical Practice Research Datalink were used. Incident RA cases and four age-, sex- and general practice-matched controls were identified from at-risk cohorts for each calendar year and followed-up for up to 5 years. Mortality rates and 95% CIs were computed. Cox proportional hazard ratios (HRs) were calculated to estimate associations and adjusted for covariates. The temporal trend in mortality was examined using the Joinpoint regression program. Data management and analysis were performed using Stata version 14. Results: A total of 21 622 cases with incident RA and 86 488 controls were included. The mortality rate of RA cases and controls was 26.90 (95% CI 25.87, 27.97) and 18.92 (18.48, 19.36)/1000 person-years, respectively. The mortality rate in RA cases did not change significantly between 1990 and 2004 but decreased by 7.7%/year between 2005 and 2009. However, the mortality rate in controls improved steadily by 2.2%/year between 1990 and 2009. RA was associated with a 32% excess risk of mortality in the entire cohort [adjusted HR 1.32 (95% CI 1.26, 1.38)], but this was only 15% in cases incident after 2006 [adjusted HR 1.15 (95% CI 1.03, 1.29)]. Similarly, the HR of death due to cardiovascular diseases decreased in cases incident in recent years. Conclusion: The mortality rate in RA cases incident after the year 2006 has declined significantly, with a trend towards a decline in death from cardiovascular diseases. This could be due to improved management of RA. However, even in cohorts from recent years, RA still associates with higher mortality rates. PMID- 29796639 TI - Incidence, presentation and management of Lyme disease in Dutch general practice. AB - Background: Little is known about the presentation and management of Lyme disease in general practice. Objective: To investigate the incidence of Lyme disease over a 6-year period, and its presentation and management in Dutch general practice. Methods: Observational study using routine data from a practice-based research network in the Netherlands with 7 practices, 24 GPs and 30000 registered patients. From 2009 to 2014, we calculated the incidence of patients presenting with Lyme disease in general practice. We analysed patient characteristics and symptoms that patients presented with at first visit. Furthermore, we analysed General Practitioners' (GPs') diagnostic and therapeutic strategies, and adherence to the national guideline. Results: Over a 6-year period, we found 212 episodes with clinical- or laboratory-based diagnosed Lyme disease, resulting in a mean incidence of 117 cases per 100000 patients per year. We did not identify a significant linear trend over time. The most frequently reported symptoms at first visit were rash (77%) and/or insect bite (58%). In 25% of patients, GPs performed a serological test, in 99% an antibiotic was prescribed and 11% were referred to a medical specialist. Frequently (in 46% of patients), the GP did not adhere to the guideline completely. Conclusion: This study shows that there is no linear trend in the incidence of Lyme disease over a 6-year period and that most patients present to GPs with unspecific symptoms like rash or insect bites. We show that GPs frequently (in 46% of patients) do not fully adhere to recommendations stated in the national guideline. PMID- 29796640 TI - RE: "GROWTH TRAJECTORIES, BREAST SIZE, AND BREAST-TISSUE COMPOSITION IN A BRITISH PREBIRTH COHORT OF YOUNG WOMEN". PMID- 29796641 TI - Tryptophan Metabolism through the Kynurenine Pathway is Associated with Endoscopic Inflammation in Ulcerative Colitis. AB - Background and Aims: Mucosal appearance on endoscopy is an important indicator of inflammatory burden and determines prognosis in ulcerative colitis (UC). Inflammation induces tryptophan metabolism along the kynurenine pathway (KP) and yields immunologically relevant metabolites. We sought to examine whether changes in serum tryptophan metabolites and tissue expression of KP enzymes are associated with UC endoscopic and histologic disease severity. Methods: Serum and mucosal samples were prospectively obtained at colonoscopy in patients with UC. Mayo disease activity scores, demographics, smoking status, medications, and outcomes were collected. Serum tryptophan metabolites were analyzed using ultra high performance liquid chromatography (uHPLC), and gas chromatography-mass spectrometry (GC-MS), and enzyme expression was determined by quantitative real time polymerase chain reaction. Metabolite and enzyme levels were compared by endoscopic subscore, clinical disease activity, time to surgery, and hospitalization. Results: This study included 99 patients with Mayo endoscopic subscores 0-3. Kynurenic acid/tryptophan ratio (KYNA/T) and expression of indolamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase, kynurinase, and kynurenine monooxygenase correlated positively with endoscopic subscore. Adjusting for age of diagnosis, smoking status, disease extent, and medications yielded significant odds of endoscopic inflammation with increasing KYNA/T (OR 1.0015, P = 0.0186) and IDO1 expression (OR 1.0635, P = 0.0215). The highest tertile ratio of KYNA/T had shorter time to surgery (P = 0.009) and hospitalization (P = 0.01) than the lowest. Conclusions: Increasing KYNA/T is closely associated with endoscopic inflammation and predictive of disease outcomes in patients with UC. These findings identify this novel metabolic association and further support the role of the KP in regulating mucosal inflammation in UC. 10.1093/ibd/izy103_video1izy103.video15788135676001. PMID- 29796642 TI - A Near-Complete Spatial Map of Olfactory Receptors in the Mouse Main Olfactory Epithelium. AB - Different regions of the mammalian nose smell different odors. In the mouse olfactory system, spatially regulated expression of >1000 olfactory receptors (ORs) along the dorsomedial-ventrolateral (DV) axis forms a topological map in the main olfactory epithelium (MOE). However, the locations of most ORs along the DV axis are currently unknown. By sequencing mRNA of 12 isolated MOE pieces, we mapped out the DV locations-as quantified by "zone indices" on a scale of 1-5-of 1033 OR genes with an estimated error of 0.3 zone indices. Our map covered 81% of all intact OR genes and 99.4% of the total OR mRNA abundance. Spatial regulation tended to vary gradually along chromosomes. We further identified putative non-OR genes that may exhibit spatial expression along the DV axis. PMID- 29796644 TI - Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation. AB - Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation. PMID- 29796645 TI - NDM-1-producing Vibrio parahaemolyticus isolated from imported seafood. PMID- 29796646 TI - Surgical Resection With Radiation Treatment Planning of Spinal Tumors. AB - BACKGROUND: The clinical paradigm for spinal tumors with epidural involvement is challenging considering the rigid dose tolerance of the spinal cord. One effective approach involves open surgery for tumor resection, followed by stereotactic body radiotherapy (SBRT). Resection extent is often determined by the neurosurgeon's clinical expertise, without considering optimal subsequent post-operative SBRT treatment. OBJECTIVE: To quantify the effect of incremental epidural disease resection on tumor coverage for spine SBRT in an effort to working towards integrating radiotherapy planning within the operating room. METHODS: Ten patients having undergone spinal separation surgery with postoperative SBRT were retrospectively reviewed. Preoperative magnetic resonance imaging was coregistered to postoperative planning computed tomography to delineate the preoperative epidural disease gross tumor volume (GTV). The GTV was digitally shrunk by a series of fixed amounts away from the cord (up to 6 mm) simulating incremental tumor resection and reflecting an optimal dosimetric endpoint. The dosimetric effect on simulated GTVs was analyzed using metrics such as minimum biologically effective dose (BED) to 95% of the simulated GTV (D95) and compared to the unresected epidural GTV. RESULTS: Epidural GTV D95 increased at an average rate of 0.88 +/- 0.09 Gy10 per mm of resected disease up to the simulated 6 mm limit. Mean BED to D95 was 5.3 Gy10 (31.2%) greater than unresected cases. All metrics showed strong positive correlations with increasing tumor resection margins (R2: 0.989-0.999, P < .01). CONCLUSION: Spine separation surgery provides division between the spinal cord and epidural disease, facilitating better disease coverage for subsequent post-operative SBRT. By quantifying the dosimetric advantage prior to surgery on actual clinical cases, targeted surgical planning can be implemented. PMID- 29796643 TI - Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations. AB - We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 and Egl-9 Family Hypoxia Inducible Factor 1 loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments. PMID- 29796647 TI - In vitro pepsin digestibility and amino acid composition in soluble and residual fractions of hydrolyzed chicken feathers. AB - Beta-keratin in poultry feathers is a structural protein that is resistant to degradation due to disulfide and hydrogen bonds. Feather meal can be a valuable feed compound if the digestibility can be increased. The objective of the present study was to analyze the effects of chemical, enzymatic, and pressure-thermic treatments for chicken feathers on solubility, in vitro protein digestibility (IVPD), and amino acid composition of solubilized and residual fractions. Two experiments were conducted. In experiment 1, models for solubility and IVPD were developed including the above factors applying a central composite face-centered design. Addition of sodium hydroxide (NaOH) and sodium sulfite (Na2SO3), and autoclaving time affected solubility and IVPD of the feather hydrolysates, but not addition of keratinolytic enzyme. In experiment 2, 7 combinations of the hydrolysis factors NaOH, Na2SO3, and autoclaving time with a predicted IVPD of 900 g/kg of DM, calculated for the sum of solubilized and residual feather fractions, were included to measure effects on IVPD and amino acid composition in each fraction. The IVPD values were higher for solubilized than residual fractions when treated with NaOH and autoclaving, but no differences were found when treated with Na2SO3 and autoclaving. Losses of cystine were substantial for all treatments, but lower for Na2SO3 than for NaOH. Furthermore, use of lower Na2SO3 concentration and longer autoclaving time reduced losses of cystine. Compared with NaOH treatments, Na2SO3 gave lower losses of threonine, arginine, serine, and tyrosine. With reference to the ideal protein profile for Atlantic salmon (Salmo salar L.), the treatments with 60 or 90 min autoclaving and 0.36 or 0.21% Na2SO3 had the highest chemical scores. The scores were generally higher for amino acids in residual than solubilized fractions, but with 90 min autoclaving and 0.21% Na2SO3 differences were small. In conclusion, hydrolysis of chicken feathers with low concentrations of Na2SO3 combined with autoclaving results in feather meal with high nutritional value for Atlantic salmon; separation of solubilized and residual fractions is not necessary. PMID- 29796649 TI - A 4-year randomized trial comparing three outreach interventions to promote screening mammograms. AB - As population health has become a focus of health care payers and providers, interest has grown in mail, phone, and other forms of outreach for improving population rates of cancer screening. Translational research is needed to compare the effectiveness and cost of low- and high-intensity behavioral outreach interventions for promoting cancer screening. The purpose of the article is to compare the effectiveness in promoting biannual mammograms of three interventions delivered over 4 years to a primary care population with a high baseline mammography adherence of 83.3%. We randomized women aged 40-84 to reminder letter only (LO arm), letter + reminder call (RC arm), and two letters + counseling call (CC arm) involving tailored education and motivational interviewing. Mammography adherence (>=1 mammogram in the previous 24 months) at four time points was determined from insurance claims records. Over 4 years, 30,162 women were randomized. At the end of 4 years, adherence was highest in the RC arm (83.0%) compared with CC (80.8%) and LO (80.8%) arms (p = .03). Only 23.5% of women in the CC arm were reached and accepted full counseling. The incremental cost per additional mammogram for RC arm women was $30.45 over the LO arm cost. A simple reminder call can increase screening mammogram adherence even when baseline adherence is high. Some more complex behavioral interventions delivered by mail and phone as in this study may be less effective, due to limited participation of patients, a focus on ambivalence, lack of follow-up, and other factors. PMID- 29796648 TI - Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training. AB - Background: The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability. Objective: The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults. Methods: In a longitudinal study, 19 healthy older adults [mean +/- SD age: 71 +/ 4 y body mass index (kg/m2): 28 +/- 3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion. Results: RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P < 0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P < 0.05) pre- and posttraining. RET increased basal MPS by 36% (P < 0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion. Conclusion: RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802. PMID- 29796650 TI - Identification of a G-quadruplex forming sequence in the promoter of UCP1. AB - G-quadruplexes are higher-order nucleic acid structures formed in G-rich sequences in DNA or RNA. G-quadruplexes are distributed in many locations in the human genome, including promoter regions, and are viewed as promising therapeutic targets. Uncoupling protein-1 (UCP1) is a mitochondrial thermogenic gene critical for energy expenditure in the form of heat in the brown adipose tissue. UCP1 is only expressed during brown fat cell differentiation and is a candidate target for treating obesity. However, the regulation of UCP1 expression is not clear. We reported here that a G-quadruplex forming sequence exists in the promoter of UCP1. The 5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4) enhanced cellular expression of UCP1 and destabilized the G-quadruplex formed by the sequence from the promoter of UCP1. Mutations in the G-quadruplex regulated the cellular activity of UCP1 promoter as evidenced by a UCP1-promoter luciferase assay. These results suggest that G-quadruplex structure is a potential target to regulate the expression of UCP1. PMID- 29796651 TI - Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 29796652 TI - Imaging of Human Neurolisteriosis: A Prospective Study of 71 Cases. AB - Background: Neurolisteriosis ranks among the most severe neurological infections. Its radiological features have not been thoroughly studied. We describe here the neuroradiological features of neurolisteriosis and assess their prognostic value. Methods: Patients with microbiologically proven neurolisteriosis were enrolled from November 2009 to October 2013 in MONALISA study. Magnetic resonance and computed tomography images were studied by 2 independent neuroradiologists. Predictors of 3-month mortality were determined using logistic regression. Results: Seventy-one patients were included; 42 were men (59%). Mean age was 64 years. Sixty patients (85%) reported signs of encephalitis, with clinical brainstem involvement in 16 (23%). Images were abnormal in 87% of cases (62/71). Main neuroradiological images were meningeal enhancement (25/71, 35%), abscess(es), or nodular image(s) evocative of abscess (10/71, 14%), hemorrhages (11/71, 15%), contrast-enhancing ventricles, or hydrocephalus (7/71, 10%). White matter images (42/71, 59%), dilated Virchow-Robin spaces (22/71, 31%), and cerebral atrophy were also reported (34/71, 48%). Brainstem involvement (meningeal enhancement, abscess) was reported in only 7/71 cases (10%). Three month survival was lower in patients with hydrocephalus or contrast-enhancing ventricles (1/7 [14%] than without [47/64, 73%], P = .005) and in patients with parenchymal images (abscess[es], nodule[s]?, or white matter images; 25/46 [54%] vs 23/25 without [92%], P = .004). Parenchymal images were associated with lower 3-month survival in the multivariable model (odds ratio 5.60, 95% confidence interval [1.42-29.6], P = .02). Conclusions: Neurolisteriosis presents as a combination of neuroradiological images, none being specific. Radiological signs of rhombencephalitis are uncommon, whereas, unexpectedly, hemorrhagic images are frequent. The negative prognostic value of parenchymal neuroradiological images was evidenced. Clinical Trials Registration: NCT01520597. PMID- 29796653 TI - THREE AUTHORS REPLY. PMID- 29796655 TI - Endoscopic Administration of Mesenchymal Stromal Cells Reduces Inflammation in Experimental Colitis. AB - Background: Mesenchymal stromal cells (MSCs) are a potential therapeutic modality in inflammatory bowel diseases (IBDs) because of their immunomodulatory and regenerative properties. However, when injected systemically, only a small portion of the cells, if any, reach the inflamed colon. In this study, we assessed whether endoscopic injections of MSCs into the intestinal wall of the inflamed colon affect the course of experimental colitis. Furthermore, we investigated if injection of aggregated MSCs in spheroids could enhance their therapeutic ability. Methods: Expression levels of in vivo MSC aggregates and in vitro MSC spheroids were compared with monolayer cultured MSCs for both anti inflammatory and pro-regenerative factors. Subsequently, MSCs and MSC spheroids were injected endoscopically in mice with established dextran sulfate sodium (DSS)-induced colitis. Results: Endoscopically injected MSCs and MSC spheroids both alleviated DSS-induced colitis. Furthermore, both in vivo and in vitro MSC spheroids showed increased expression of factors important for immunomodulation and tissue repair, compared with monolayer cultured MSCs. Despite differential expression of these factors, MSC spheroids showed similar clinical efficacy in vivo as single-cell suspension MSCs. Analysis of serum samples and colon homogenates showed that local MSC therapy resulted in increased levels of interferon-gamma, indoleamine 2,3-dixoygenase, and interleukin-10. Conclusions: Endoscopic injections of MSCs and MSC spheroids in the inflamed colon attenuate DSS-induced colitis. Our data show that endoscopic injection can be a feasible and effective novel application route for MSC therapy in patients with luminal IBD. PMID- 29796654 TI - Rapid Communication: Porcine CRTC3 gene clone, expression pattern, and its regulatory role in intestinal epithelial cells. AB - In the current study, we aimed to clone the full-length cDNA of porcine CRTC3 (pCRTC3) gene and examine its expression pattern and function in intestinal epithelial cells. The full-length cDNA sequence of pCRTC3 was 2,173 bp (GenBank accession no. MF964215), with a 1,860-bp open reading frame encoding a 620-AA protein. Comparison of the deduced AA sequence with different species including human, mouse, rat, Papio, cattle, and rabbit showed 89% to 91.9% similarity. The pCRTC3 was highly expressed in small intestine and spleen, to a lesser degree in lung, liver, and adipose tissue, and was expressed at a low but detectable level in skeletal muscle, kidney, and heart. In addition, high protein levels of pCRTC3 were found in IPEC-J2 cells, in which pCRTC3 was mainly localized in cytoplasm. Furthermore, we demonstrated that knockdown of pCRTC3 significantly decreased the expression of the porcine tight junction-related genes including zonula occludens 1 (ZO-1), ZO-2, occludin, and claudin-1 by 57.88% (P < 0.01), 40.19% (P < 0.01), 51.59% (P < 0.01), and 35.70% (P < 0.05), respectively. Taken together, we first cloned the full-length sequence of pCRTC3 and revealed the tissue-specific expression pattern, localization, and function of pCRTC3 in regulating the expression of intestinal tight junction-related genes. This study could provide some useful information for understanding the function of CRTC3 in pigs. PMID- 29796656 TI - Construction of a high-efficiency gene-targeting system in brewing-wine Aspergillus oryzae industrial strain used in direct xylitol conversion from xylan. PMID- 29796657 TI - The Possibility of Using Isolated Alkaloid Compounds and Crude Extracts of Piper retrofractum (Piperaceae) as Larvicidal Control Agents for Culex quinquefasciatus (Diptera: Culicidae) Larvae. AB - Culex quinquefasciatus is a common domestic mosquito that is widespread in many areas of Thailand and serves as a southeastern vector of Japanese encephalitis. The present study investigated the acute toxicity of crude extracts and alkaloid compounds of Piper retrofractum (Piperales: Piperaceae) in Cx. quinquefasciatus third instar larvae. P. retrofractum was sequentially extracted using hexane, dichloromethane, ethyl acetate, and methanol, and the crude extracts were tested on mosquito larvae. Detoxification and neuroenzymes were analyzed to establish the mode of action. Acute toxicity was assessed on Poecilia reticulata (Cyprinodontiformes: Poeciliidae) to determine the possibility of toxicity in a nontarget species. Our results showed crude hexane extract had the highest toxicity in Cx. quinquefasciatus (0.9 ppm). Piperine and piperanine, which are alkaloid compounds from the crude hexane extract, showed LC50 values of 0.27 and 2.97 ppm, respectively, after 24 h of exposure. All the crude extracts showed low toxicity in P. reticulata compared with that in the mosquito larvae. The carboxylesterase, glutathione-S-transferase, and acetylcholinesterase activities in Cx. quinquefasciatus were reduced after treatment with all the extracts and the two alkaloid compounds. Thus, P. retrofractum shows larvicidal effects against Cx. quinquefasciatus and low toxicity for nontarget species. Thus, P. retrofractum could be a choice for controlling Cx. quinquefasciatus. PMID- 29796658 TI - BCL2 Regulates Differentiation of Intestinal Fibroblasts. AB - Background: Fibrosis in patients with Crohn's disease (CD) results from an imbalance toward excessive fibrous tissue formation driven by fibroblasts. Activation of fibroblasts is linked to the B-cell lymphoma 2 (BCL2) family, which is involved in the induction of apoptosis. We investigated the impact of BCL2 repression on fibrogenesis. Methods: The model of dextran sodium sulfate (DSS) induced chronic colitis and the heterotopic transplantation model of fibrosis were used. Following the administration of the BCL2 antagonist (ABT-737, 50 mg/kg/d), collagen layer thickness and hydroxyproline (HYP) content were determined. Fibroblasts were stimulated with the BCL2 antagonist (0.01-100 uM). BCL2, alpha smooth muscle actin (alphaSMA), and collagen I (COL1A1) were determined by quantitative polymerase chain reaction (qPCR), immunofluorescence microscopy (IF), and western blot (WB). mRNA expression pattern was determined by next-generation sequencing (NGS). Results: Collagen layer thickness was significantly decreased in both DSS-induced chronic colitis and the transplantation model of fibrosis upon BCL2 antagonist administration compared with vehicle. Decreased HYP content confirmed the preventive effects of the BCL2 antagonist on fibrosis. In vitro, a significant increase in PI+/annexin V+ human colonic fibroblasts was determined by fluorescence-activated cell sorting upon treatment with high-dose BCL2 antagonist; at a lower dose, alphaSMA, COL1A1, and TGF were decreased. NGS, IF, and qPCR revealed decreased expression and nuclear translocation of GATA6 and SOX9, known for reprogramming fibroblasts. Conclusion : BCL2 antagonist administration partially prevented fibrogenesis in both fibrosis models. The BCL2 antagonist reduced the expression of TGFbeta-induced factors involved in differentiation of myofibroblasts, and therefore might represent a potential treatment option against CD-associated fibrosis. PMID- 29796659 TI - Comparing two techniques for viscosity measurements in poultry feedstuffs: does it render similar conclusions? AB - Viscosity of intestinal contents is known to affect digestion and absorption of nutrients. In most poultry studies, intestinal viscosity has been measured only after complete removal of solid particles by centrifugation. Centrifugation may however remove particles that contribute to viscosity, hence giving rise to an underestimation of viscosity. Two viscosity measurement techniques, one including a centrifugation step (Brookfield) and the other without (Haake), were compared in-vitro to assess whether both techniques result in similar conclusions regarding viscosity in feedstuffs. Two sets of feedstuff preparations were used. The first set was prepared with different combinations of milled feedstuffs in order to have a wide range of viscosity: 100% corn, 25% corn + 75% wheat, 100% wheat, 90% wheat + 10% rye, all mixed with distilled water. In the second set, barley was incubated with different beta-glucanases, and soybean and sunflower meal were incubated with different pectinases, again all mixed with distilled water. Viscosity was assessed using both techniques (Haake and Brookfield equipments) at six different time points. To evaluate the extent of agreement between the two methods, the Lin's concordance correlation coefficient (CCC) was assessed using the percentage of increase in viscosity within each method, based on pairwise feedstuffs comparison (first set), or relative to the feedstuff without enzyme (second set). The rate of the agreement between the two methods was substantial for the first set of feedstuffs (66%) and for the barley diets incubated with beta-glucanases (69%), whereas the CCC score for the soybean meal diets was very poor (2%) and fair for the sunflower meal diets, incubated with pectinases (32%). The lack of agreement for the latter can be explained by the limited variation in viscosity in these low-viscous mixtures. Although the two techniques are considerably different (e.g., with or without preceding particle removal), they seem to render similar conclusions when applied to poultry feedstuffs to identify distinct differences under the tested circumstances. PMID- 29796660 TI - Smoking and Physical Activity Explain the Increased Mortality Risk Following Marital Separation and Divorce: Evidence From the English Longitudinal Study of Ageing. AB - Background: Marital separation and divorce are associated with an increased risk of early mortality, but the specific biobehavioral pathways that explain this association remain largely unknown. Purpose: This study sought to identify the putative psychological, behavioral, and biomarker variables that can help explain the association of being separated or divorced and increased risk for early mortality. Methods: Using data from the English Longitudinal Study of Ageing, a representative community sample of aging adults (N = 5,786), we examined the association of marital status and life satisfaction, health behaviors measured 2 years later, biomarkers measured 4 years later, and mortality outcomes from the subsequent 4 years. Results: Consistent with prior literature, older adults who were separated/divorced evidenced greater risk of mortality relative to those in intact marriages over the study period, OR = 1.46, 95% CI [1.15, 1.86]. Marital status was associated with lower levels of life satisfaction, beta = -0.22 [ 0.25, -0.19] and greater likelihood of smoking 2 years later beta = 0.17 [0.13, 0.21]. Lower life satisfaction predicted less frequent physical activity 2 years later, beta = 0.07 [0.03, 0.10]. Smoking, but not physical activity, predicted poorer lung functioning 2 years later, beta = -0.43 [-0.51, -0.35], and poorer lung function predicted increased likelihood of mortality over the following 4 years, beta = -0.15 [-0.27, -0.03]. There was a significant total indirect effect of marital status on mortality through these psychological, behavioral, and biomarker variables, beta = 0.03 [0.01, 0.05], which fully explained this mortality risk. Conclusions: For separated/divorced adults, differences in life satisfaction predict health behaviors associated with poorer long-term lung function, and these intermediate variables help explain the association between marital dissolution and increased risk of earlier mortality. PMID- 29796662 TI - Letter: The In Vivo Antitumoral Effects of Lipopolysaccharide Against Glioblastoma Multiforme are Mediated in Part by Toll-Like Receptor 4. PMID- 29796663 TI - The therapeutic prospect of crosstalk between prokaryotic and eukaryotic organisms in the human gut. AB - The peaceful phenomenon of the co-evolution between the prokaryotes (microbiota) and the eukaryotes (parasites including protozoa and helminths) in the animal gut has drawn the researchers' attention. Importantly, exploring the potential of helminths for therapeutic uses was one of the reasons behind understanding the physiological and immunological crosstalk existing between them. Here we discuss the interactive immunological associations of helminths and microbial responses individually and in combination with their hosts. Considering that there is probably crosstalk between eukaryotic organisms like helminths and protozoa with their host's gut microbiota, in this review we searched the literature identifying the privileged and favourable relationship generated between them in the host. Understanding the possibilities of the role of helminths along with gut microbiota as a black box would certainly help decode the therapeutic intrusion with helminths in experimental clinical trials, and a successful trial could be used to consider possible future and safe treatments for various immune inflammatory diseases in humans. PMID- 29796661 TI - Decreased incidence of diabetes in patients with gout using benzbromarone. AB - Objective: Insulin resistance is inversely correlated with the clearance rate of uric acid, which may indicate that improvement in the clearance rate of uric acid could reduce insulin resistance. Considering the increased prevalence of diabetes mellitus (DM) in the gout population, this study evaluated the effects of benzbromarone, a uricosuric agent, on the incidence of DM in the gout population. Methods: We used data from the Taiwan National Health Insurance program. The benzbromarone user cohort included 8678 patients; each patient was age- and sex matched with one benzbromarone non-user who was randomly selected from the gout population. The Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of DM in the gout population. Results: The incidence of DM was significantly lower in benzbromarone users than in benzbromarone non-users [adjusted hazard ratio (HR) = 0.86; 95% CI: 0.79, 0.94]. The HR for the incidence of DM was lower in male benzbromarone users (adjusted HR = 0.77; 95% CI: 0.69, 0.86) than in benzbromarone non-users. An analysis of three age groups (<40, 40-59 and ?60 years) indicated that the HRs of the age groups of 40-59 years (adjusted HR = 0.86; 95% CI: 0.76, 0.98) and ?60 years (adjusted HR = 0.82; 95% CI: 0.71, 0.94) were significantly lower among benzbromarone users than among benzbromarone non-users. Conclusion: In the gout population, the incidence of DM was lower in benzbromarone users than in benzbromarone non-users. PMID- 29796664 TI - Intervention Fidelity Within Trials of Infant Feeding Behavioral Interventions to Prevent Childhood Obesity: A Systematic Review. AB - Background: Intervention fidelity refers to whether an intervention has been implemented as intended. Trials of infant feeding behavioral interventions to prevent childhood obesity show inconsistent evidence of effectiveness. However, intervention fidelity has not been previously explored within these trials, limiting interpretation of findings. Purpose: To review the use and/or reporting of strategies to enhance and assess intervention fidelity within trials of infant feeding interventions to prevent childhood obesity, and their association with study quality, effectiveness, and publication year. Methods: Seven electronic databases were searched, with articles screened for inclusion by two reviewers. The National Institutes of Health Behaviour Change Consortium fidelity checklist was used to assess use and/or reporting of fidelity strategies across five domains (design, provider training, delivery, receipt, and enactment). Results: Ten trials (16 papers) were identified. Average use/reporting of fidelity strategies was moderate (54%), ranging from 28.9% to 76.7%. Levels of use/reporting ranged from 15.9% in the domain of provider training to 95% for enactment. No association was found between these levels and study quality, effectiveness, or publication year. Conclusions: The moderate use/reporting of fidelity strategies within trials of infant feeding interventions suggests that previous findings of inconsistent effectiveness may not fully reflect the intended interventions. The review highlights key considerations for improving future research, both in the area of behavioral infant feeding and wider behavior change literature. This includes improving reporting across all fidelity domains and ensuring an enhanced focus on provider training and control group content to optimize the translation of research into practice. PROSPERO Registration number: CRD42016033492. PMID- 29796665 TI - A unique fucosylated chondroitin sulfate type II with strikingly homogeneous and neatly distributed alpha-fucose branches. AB - Fucosylated chondroitin sulfates (FCSs) and sulfated fucans (SFs) are conspicuous components of the body wall of sea cucumbers (Holothuroidea). FCSs are composed of a central core of chondroitin sulfate (CS) decorated with branches of mono- or both mono- and disaccharides of alpha-fucose (FCS types I and II, respectively). FCSs type II have heterogeneous and irregularly distributed alpha-fucose branches; however, the novel FCS type II from Holothuria lentiginosa described herein via solution nuclear magnetic resonance has strikingly homogeneous alpha fucose branches neatly distributed along its CS core. This FCS is built up of three distinct sequential units composed of the typical CS disaccharides of FCSs, rich in beta-galactosamine-4,6diS, decorated with branches of alpha-Fucp-2,4diS, alpha-Fucp-3,4diS or alpha-Fucp[1->3]alpha-Fucp-4S[1-> linked to the position 3- of the beta-glucuronic acid. Conformational analyses of these repetitive units revealed a fairly rigid structure despite of the high sulfate content of their alpha-fucose branches. We also determined the structure of the SF from H. lentiginosa as a repetitive tetrasaccharide sequence composed of ->3]alpha-Fucp 2,4diS[1->3]alpha-Fucp[1->3]alpha-Fucp-2S[1->3]alpha-Fucp-2S[1->. Furthermore, we determined that the nonsulfated alpha-fucose units present in FCS type II did not interfere with their anticoagulant potencies and affinities to calcium. FCS is an autapomorphic molecular character of the class Holothuroidea and the composition of their alpha-fucose branches differs in a species-specific manner. Branches containing alpha-Fucp-2,4diS are the most common within the extant holothurians, being found in 90% of the FCSs characterized thus far. PMID- 29796666 TI - Lactobacillus species increase the survival of Galleria mellonella infected with Candida albicans and non-albicans Candida clinical isolates. AB - Investigation into new therapeutic strategies, such as the use of bacterial isolates with probiotic characteristics, has increased in importance due to the high incidence of Candida albicans and non-albicans Candida infections. This study evaluates Lactobacillus paracasei, Lactobacillus fermentum and Lactobacillus rhamnosus strains as prophylactic and therapeutic agents against infection caused by Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis in a Galleria mellonella model. Prophylactic treatment provided greater benefits during Candida spp. infection, increasing G. mellonella survival, compared to therapeutic treatment. This study demonstrated that the different Lactobacillus species are potent prophylactic agents of Candida species infection. PMID- 29796668 TI - FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice. AB - Neurotensin (NT), a 13 amino-acid peptide, is predominantly released from enteroendocrine cells of the small bowel in response to fat ingestion. Free fatty acid receptors (FFARs) FFAR1 and FFAR4 regulate secretion of gut hormones and insulin. Here, we show that docosahexaenoic acid, a long-chain fatty acid, has the most dramatic effect on NT release. FFAR1 agonists slightly stimulate and FFAR4 agonists dramatically stimulate and amplify NT secretion. Double knockdown of FFAR1 and FFAR4 decreases NT release, whereas overexpression of FFAR4, but not FFAR1, increases NT release. Administration of cpdA, an FFAR4 agonist, but not TAK-875, a selective FFAR1 agonist, increases plasma NT levels and further increases olive oil-stimulated plasma NT levels. Inhibition of MAPK kinase (MEK)/ERK1/2 decreased fatty acid-stimulated NT release but increased AMP activated protein kinase (AMPK) phosphorylation. In contrast, inhibition of AMPK further increased NT secretion and ERK1/2 phosphorylation mediated by FFAR1 or FFAR4. Our results indicate that FFAR4 plays a more critical role than FFAR1 in mediation of fat-regulated NT release and in inhibitory crosstalk between MEK/ERK1/2 and AMPK in the control of NT release downstream of FFAR1 and FFAR4. PMID- 29796667 TI - Stability of local secondary structure determines selectivity of viral RNA chaperones. AB - To maintain genome integrity, segmented double-stranded RNA viruses of the Reoviridae family must accurately select and package a complete set of up to a dozen distinct genomic RNAs. It is thought that the high fidelity segmented genome assembly involves multiple sequence-specific RNA-RNA interactions between single-stranded RNA segment precursors. These are mediated by virus-encoded non structural proteins with RNA chaperone-like activities, such as rotavirus (RV) NSP2 and avian reovirus sigmaNS. Here, we compared the abilities of NSP2 and sigmaNS to mediate sequence-specific interactions between RV genomic segment precursors. Despite their similar activities, NSP2 successfully promotes inter segment association, while sigmaNS fails to do so. To understand the mechanisms underlying such selectivity in promoting inter-molecular duplex formation, we compared RNA-binding and helix-unwinding activities of both proteins. We demonstrate that octameric NSP2 binds structured RNAs with high affinity, resulting in efficient intramolecular RNA helix disruption. Hexameric sigmaNS oligomerizes into an octamer that binds two RNAs, yet it exhibits only limited RNA-unwinding activity compared to NSP2. Thus, the formation of intersegment RNA RNA interactions is governed by both helix-unwinding capacity of the chaperones and stability of RNA structure. We propose that this protein-mediated RNA selection mechanism may underpin the high fidelity assembly of multi-segmented RNA genomes in Reoviridae. PMID- 29796669 TI - Regulatory RNA in Mycobacterium tuberculosis, back to basics. AB - Since the turn of the millenium, RNA-based control of gene expression has added an extra dimension to the central dogma of molecular biology. Still, the roles of Mycobacterium tuberculosis regulatory RNAs and the proteins that facilitate their functions remain elusive, although there can be no doubt that RNA biology plays a central role in the baterium's adaptation to its many host environments. In this review, we have presented examples from model organisms and from M. tuberculosis to showcase the abundance and versatility of regulatory RNA, in order to emphasise the importance of these 'fine-tuners' of gene expression. PMID- 29796670 TI - HotSpot Wizard 3.0: web server for automated design of mutations and smart libraries based on sequence input information. AB - HotSpot Wizard is a web server used for the automated identification of hotspots in semi-rational protein design to give improved protein stability, catalytic activity, substrate specificity and enantioselectivity. Since there are three orders of magnitude fewer protein structures than sequences in bioinformatic databases, the major limitation to the usability of previous versions was the requirement for the protein structure to be a compulsory input for the calculation. HotSpot Wizard 3.0 now accepts the protein sequence as input data. The protein structure for the query sequence is obtained either from eight repositories of homology models or is modeled using Modeller and I-Tasser. The quality of the models is then evaluated using three quality assessment tools WHAT_CHECK, PROCHECK and MolProbity. During follow-up analyses, the system automatically warns the users whenever they attempt to redesign poorly predicted parts of their homology models. The second main limitation of HotSpot Wizard's predictions is that it identifies suitable positions for mutagenesis, but does not provide any reliable advice on particular substitutions. A new module for the estimation of thermodynamic stabilities using the Rosetta and FoldX suites has been introduced which prevents destabilizing mutations among pre-selected variants entering experimental testing. HotSpot Wizard is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard. PMID- 29796671 TI - Prolonged Exposure to Monosodium Glutamate in Healthy Young Adults Decreases Perceived Umami Taste and Diminishes Appetite for Savory Foods. AB - Background: Research suggests that increased consumption of sweet, salt, or fat is associated with diminished perceived taste intensity and shifted preferences for the respective stimulus. It is unknown whether a similar effect occurs with the consumption of umami. Objective: The aim of the study was to investigate the influence of habitual exposure to umami stimuli on umami taste perception, hedonics, and satiety. Methods: Fifty-eight healthy men (n = 16) and women (n = 42) participated in a parallel-group, randomized controlled study. The normal weight [mean +/- SD body mass index (kg/m2): 21.8 +/- 2.2] group of young adults (mean +/- SD age: 22.7 +/- 6.2 y) consumed vegetable broth daily for 4 wk. The broth for the treatment group (n = 28) was supplemented with 3.8 g monosodium glutamate (MSG), whereas the control group (n = 30) consumed a sodium-matched broth without MSG. Perceived umami taste intensity and discrimination in MSG solutions; liking, wanting, and preference of a variety of umami-rich foods; satiation and satiety from an ad libitum meal; and anthropometric measures were evaluated at baseline and at week 4. General linear models assessed the effect of treatment on change from baseline for all outcomes and tested for effect modification of sex. Results: Relative to controls, increased consumption of MSG for 4 wk diminished umami taste in women (8.4 units on generalized Labeled Magnitude Scale; 95% CI: -13.8, -3.1 units; P = 0.013). The desire for and intake of savory foods decreased after MSG treatment in both sexes with an ad libitum meal (desire: -7.7 units; 95% CI: -13.7, -1.7 units; P = 0.04; intake: -36 g; 95% CI: -91, 19 g; P = 0.04). Conclusion: Our results highlight that a month-long diet high in umami stimuli attenuates perceived umami taste and appetite for savory foods in a young, healthy population. Our findings contribute to the understanding of food choice, a factor in the development and maintenance of obesity, as well as the etiology of protein-related health conditions such as osteoporosis and kidney disease. This study is registered at www.clinicaltrials.gov as NCT03010930. PMID- 29796673 TI - Alice Hamilton, 1869-1970, 'The Mother of Occupational Medicine'. PMID- 29796674 TI - Temporary work and depressive symptoms. PMID- 29796672 TI - Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer. AB - Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on RNA (ADARs). Dysregulated A-to-I editing has been implicated in various diseases, including cancers. However, the precise factors governing the A-to-I editing and their physiopathological implications remain as a long-standing question. Herein, we unravel that DEAH box helicase 9 (DHX9), at least partially dependent of its helicase activity, functions as a bidirectional regulator of A-to-I editing in cancer cells. Intriguingly, the ADAR substrate specificity determines the opposing effects of DHX9 on editing as DHX9 silencing preferentially represses editing of ADAR1-specific substrates, whereas augments ADAR2-specific substrate editing. Analysis of 11 cancer types from The Cancer Genome Atlas (TCGA) reveals a striking overexpression of DHX9 in tumors. Further, tumorigenicity studies demonstrate a helicase-dependent oncogenic role of DHX9 in cancer development. In sum, DHX9 constitutes a bidirectional regulatory mode in A-to-I editing, which is in part responsible for the dysregulated editome profile in cancer. PMID- 29796676 TI - "Turn on the Lights". PMID- 29796675 TI - Strabismus Postoperative Instructions to Patients and Parents. PMID- 29796677 TI - An Exciting Couple. PMID- 29796678 TI - Avoid Performing Surgery on the Wrong Eye in Pediatric Ophthalmology. PMID- 29796679 TI - Wrong-Site Surgery in Pediatric Ophthalmology. AB - PURPOSE: To determine the prevalence of pediatric ophthalmologists who have performed wrong-site surgery, propose risk factors leading to these errors, and assess the effectiveness of the Universal Protocol in preventing them. METHODS: Approximately 1,000 pediatric ophthalmology surgeons were invited to complete an anonymous 10-question survey. Respondents were divided into two groups: those who performed or attempted wrong-site surgery (wrong-site surgery group) and those who had never performed a wrong-site surgery (intended surgical site group). The risk factors (ie, marking procedure, years in practice, surgical experience, adherence to the Universal Protocol time-out, and operating room factors) were compared between groups. RESULTS: Of the 156 respondents, 56.4% never performed, 9% attempted, and 34.6% performed a wrong-site surgery. The use of any procedure to mark the eye decreased the likelihood of a wrong-site surgery by 61% (odds ratio [OR] = 0.39; P = .069). A lower likelihood of error occurred when a single individual led the time-out and multiple individuals participated in checking the accuracy of the time-out. Surgeons in practice for less than 15 years had a lower likelihood of performing a wrong-site surgery (OR = 0.37; 95% confidence interval [CI] = 0.19 to 0.72; P = .003). Factors not significantly associated with wrong site surgeries were the number of surgeries performed per year (OR = 0.66; 95% CI = 0.35 to 1.24; P = .20) and the number of operating rooms used. CONCLUSIONS: In concordance with previous reports of other surgical specialties, self-reported error in pediatric ophthalmology is not uncommon. This study highlighted important practices that can be easily adopted by surgeons to decrease the likelihood of wrong-site surgeries. First, marking the surgical site must be part of the preoperative preparation. Second, a single designated individual should lead the time-out and the surgeon should be directly involved in all steps of the time-out process. Third, surgeons who have been in practice for more than 15 years may require additional safeguards to ensure that the correct surgery is performed and to monitor their complacency. [J Pediatr Ophthalmol Strabismus. 2018;55(3):152-158.]. PMID- 29796681 TI - Sclopetaria Following Penetrating Orbital Arrow. PMID- 29796680 TI - Comparison Study of Funduscopic Examination Using a Smartphone-Based Digital Ophthalmoscope and the Direct Ophthalmoscope. AB - PURPOSE: To assess the ease of use of the D-EYE digital ophthalmoscope (D-EYE Srl, Padova, Italy) in retinal screening against the conventional direct ophthalmoscope. The digital ophthalmoscope used comprised a smartphone equipped with a D-EYE lens that produces digital retinal images. METHODS: Twenty-five medical students were given 30 minutes of instruction regarding how to use a direct ophthalmoscope and D-EYE digital ophthalmoscope by a pediatric ophthalmologist. Afterwards, they used two methods to view the fundus under dim light on two undilated volunteer participants under supervision of the pediatric ophthalmologist. Each student had to describe their findings and show the video taken from the smartphone to the pediatric ophthalmologist. Students also completed a survey rating their experience using each method. RESULTS: Ninety-two percent of the medical students preferred the D-EYE digital ophthalmoscope to the direct ophthalmoscope. Students were also able to identify the optic nerve and macula in a shorter amount of time and review the images to confirm their findings. Overall, the medical students showed a strong preference for the D-EYE digital ophthalmoscope that was statistically significant (P < .001). CONCLUSIONS: The D-EYE digital ophthalmoscope is a practical device that could be incorporated into medical education and clinical practice. Survey results revealed that most students preferred the D-EYE digital ophthalmoscope due to the recording features and larger image of the fundus. [J Pediatr Ophthalmol Strabismus. 2018;55(3):201-206.]. PMID- 29796682 TI - Author's reply: Haematologist-reviewed peripheral blood smear in paediatric practice. PMID- 29796683 TI - Authors' reply: Medication-related osteonecrosis of the jaw in osteoporotic patients: prevention and management. PMID- 29796684 TI - Right hemicolectomy for acute appendicitis secondary to breast cancer metastases. PMID- 29796685 TI - Epidemiology of paediatric poisoning presenting to a children's emergency department in Singapore over a five-year period. AB - INTRODUCTION: Paediatric poisoning accounts for 1% of daily emergency department presentations. The aim of this study was to review the characteristics and outcomes of paediatric patients who presented with drug overdose over a five-year period. METHODS: We performed a retrospective review of paediatric poisoning cases at KK Women's and Children's Hospital (KKH), the largest children's public hospital in Singapore, from 1 January 2009 to 31 December 2013. RESULTS: A total of 1,208 cases of poisoning were seen in KKH's Department of Children's Emergency during the study period. The gender distribution was about equal, with a slight male predominance. The majority of the poisoning cases were accidental. Slightly more than half of the intentional ingestions were of paracetamol and the majority were female patients belonging to the 12-16 year age group. The bulk of poisonings occurred in children aged 1-4 via the oral route, slightly more than half of the oral ingestions consisted of oral medications and a sizeable portion were of household liquids. Mothballs and silica gels accounted for almost a quarter of the solid household products ingested. Slightly less than half of the patients required admission and only a small portion of the admitted patients required intensive or high dependency care. CONCLUSION: The prognosis of paediatric patients who presented with poisoning in our study was good, with a short median length of stay for those admitted and no fatalities being reported across the span of five years. PMID- 29796687 TI - Author's reply: Cytomegalovirus (CMV) hepatitis: an uncommon complication of CMV reactivation in drug reaction with eosinophilia and systemic symptoms. PMID- 29796688 TI - Lymphomatoid Papulosis (LyP) Associated with Diffuse Large B-cell Lymphoma and Cutaneous Anaplastic Large Cell Lymphoma: LyP as a Haematological Malignancy related Dermadrome. PMID- 29796689 TI - Epidemiological Analysis of Major Complications Requiring Medical Intervention in Patients with Neurofibromatosis 1. AB - Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1. PMID- 29796686 TI - Traditional Chinese medicine: herb-drug interactions with aspirin. AB - Traditional Chinese medicine (TCM)-based herbal therapies have gained increasing popularity worldwide, raising concerns of its efficacy, safety profile and potential interactions with Western medications. Antithrombotic agents are among the most common prescription drugs involved in herb-drug interactions, and this article focused on aspirin, one of the most widely used antiplatelet agents worldwide. We discussed herbs that have potential interactions by exploring Western and TCM approaches to thrombotic events. Common TCM indications for these herbs were also highlighted, including possible scenarios of their concurrent usage with aspirin. With greater awareness and understanding of potential herb drug interactions, TCM and Western physicians may collaborate more closely to identify, treat and, most importantly, prevent adverse drug events. PMID- 29796690 TI - Desmoglein 4 Mutation Underlies Autosomal Recessive Keratosis Pilaris Atrophicans. PMID- 29796691 TI - Atopic Dermatitis Linked Cytokine Interleukin-31 Induced Itch Mediated via a Neuropeptide Natriuretic Polypeptide B. PMID- 29796692 TI - The impact of desorption kinetics from albumin on hepatic extraction efficiency and hepatic clearance: a model study. AB - Until now, the question whether slow desorption of compounds from transport proteins like the plasma protein albumin can affect hepatic uptake and thereby hepatic metabolism of these compounds has not yet been answered conclusively. This work now combines recently published experimental desorption rate constants with a liver model to address this question. For doing so, the used liver model differentiates the bound compound in blood, the unbound compound in blood and the compound within the hepatocytes as three well-stirred compartments. Our calculations show that slow desorption kinetics from albumin can indeed limit hepatic metabolism of a compound by decreasing hepatic extraction efficiency and hepatic clearance. The extent of this decrease, however, depends not only on the value of the desorption rate constant but also on how much of the compound is bound to albumin in blood and how fast intrinsic metabolism of the compound in the hepatocytes is. For strongly sorbing and sufficiently fast metabolized compounds, our calculations revealed a twentyfold lower hepatic extraction efficiency and hepatic clearance for the slowest known desorption rate constant compared to the case when instantaneous equilibrium between bound and unbound compound is assumed. The same desorption rate constant, however, has nearly no effect on hepatic extraction efficiency and hepatic clearance of weakly sorbing and slowly metabolized compounds. This work examines the relevance of desorption kinetics in various example scenarios and provides the general approach needed to quantify the effect of flow limitation, membrane permeability and desorption kinetics on hepatic metabolism at the same time. PMID- 29796693 TI - Neonatal Outcomes in Total Anomalous Pulmonary Venous Return: The Role of Prenatal Diagnosis and Pulmonary Venous Obstruction. AB - The objective of this study is to evaluate neonatal outcomes of total anomalous pulmonary venous return (TAPVR) and identify fetal echocardiography findings associated with preoperative pulmonary venous obstruction (PPVO). This retrospective study evaluated TAPVR cases from 2005 to 2014 for preoperative and postoperative outcomes based on prenatal diagnosis, PPVO, and heterotaxy syndrome. Fetal pulmonary and vertical vein Dopplers were analyzed as predictors of PPVO. Of 137 TAPVR cases, 12% were prenatally diagnosed; 60% had PPVO, and 21% had heterotaxy. Of the prenatally diagnosed patients, 63% also had heterotaxy. TAPVR repair was performed in 135 cases and survival to discharge was 82% (112/137). Heterotaxy was the only independent predictor of mortality on multiple regression analysis [OR 5.5 (CI 1.3-16.7), p = 0.02]. PPVO was associated with preoperative acidosis, need for inhaled nitric oxide, and more emergent surgery, but not postoperative mortality. Fetal vertical vein Doppler peak velocity > 0.74 m/s mmHg predicted PPVO (93% sensitivity; 83% specificity) while pulmonary vein Doppler did not. TAPVR has severe neonatal morbidity and mortality with low prenatal diagnosis rates in the absence of heterotaxy. Patients with obstructed TAPVR had greater preoperative morbidity, but only heterotaxy was independently associated with increased postoperative mortality. Vertical vein velocity helped prenatally identify those at risk of PPVO. PMID- 29796694 TI - Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention. AB - PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T-category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)2-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)2-L and DSF nanoparticles, indicating an improved synergistic antitumor effect. CONCLUSIONS: The Cu(OI)2-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper. PMID- 29796712 TI - Right Versus Left Colon Cancer: Resectable and Metastatic Disease. AB - OPINION STATEMENT: Colorectal cancer does not represent a single anatomic entity and side of origin has a key impact on prognosis and response to different systemic therapies. Compared to tumours arising in left colon, right colorectal cancers rely on the activation of different molecular pathways (e.g. BRAF mutation and MSI status). From a clinical point of view, this results in a different response to anti-EGFR agents. Current guidelines suggest the use of cetuximab or panitumumab in RAS wild-type disease and left colon cancer especially for cytoreduction/conversion purposes, since the expected benefit in right colon cancer is absent or clinically modest. The prognostic role of microbiota in colorectal cancer disease deserves more clarification before being considered in common clinical practice. Screening policies could also be affected by these new acquisitions. At the moment, sidedness should be considered as a strong prognostic variable and a surrogate predictor of different activity of anti-EGFR agents in the metastatic setting. Its role in early stages of resected disease is still uncertain. PMID- 29796714 TI - Nonequilibrium processes in meta-stable media?. AB - Meta-stable systems are those staying in the local equilibrium state: being slightly deviated from it they return to the equilibrium, but in case deviation surpasses a critical value those systems fall down to another equilibrium state. Chemically reacting gaseous mixture provides a typical example of a meta-stable system. The paper is aimed at numerical and experimental investigation of detonation initiation in hydrogen-air mixtures due to focusing of a shock wave reflected inside a wedge. Both numerical and experimental investigations were conducted. Comparison of numerical and experimental results made it possible to validate the developed 3D transient mathematical model of chemically reacting gas mixture flows incorporating hydrogen-air mixtures. Kinetic schemes and turbulence models were improved based on comparison of numerical and experimental results. Several different flow scenarios manifest in the reflection of shock waves all being dependent on the incident shock wave intensity: reflection of the shock wave with lagging behind the combustion zone, formation of a detonation wave in reflection and focusing, and intermediate transient regimes. PMID- 29796715 TI - Sickle Cell Trait and Sudden Death. AB - Sickle cell trait has long been considered a benign condition but continues to be the leading cause of death in young African Americans in military basic training and civilian organized sports. There continues to be a great deal of controversy surrounding sickle cell trait and its association with exercise-related morbidity and sudden death. Even though sickle cell trait has a high prevalence among African Americans, many clinicians believe the potential adverse consequences should have been mitigated by actions such as universal screening in the USA at birth for sickle hemoglobin, National Collegiate Athletic Association (NCAA) rule changes, and changes in the US Military boot camp system. Sudden death due to periods of extreme physical exertion continues to occur in individuals with sickle cell trait. PMID- 29796716 TI - Synthesis and anticancer evaluation of some novel pyrimido[5,4-e][1,2,4]triazines and pyrazolo[3,4-d]pyrimidine using DMF-DMA as methylating and cyclizing agent. AB - BACKGROUND: Described a series of main target compounds pyrimido[5,4 e][1,2,4]triazines is obtained via condensation of 6-hydrazinyluracil with different aromatic aldehydes to give the hydrazones followed by nitrosation with HNO2 then intramolecular cyclization. On the other hand, pyrazolopyrimidines can be obtained by the reaction of hydrazones with dimethylformamide-dimethylacetal (DMF-DMA), DMF-DMA in the presence of DMF or by refluxing the hydrazinyluracil with DMF-DMA in the presence of DMF directly. The newly synthesized compounds are evaluated in vitro for their anticancer activity against human lung carcinoma (A549). RESULTS: A newly substituted compounds of benzaldehyde-pyrimidin-4 yl)hydrazones (5a-f), pyrimido[5,4-e][1,2,4]triazines 6a-e, arylethylidenehydrazinylpyrimidine 7a,b and pyrazolopyrimidines 9,11 are screened for cytotoxic activity against human lung carcinoma (A549) cell line. They exhibited a good yield. Compound 6b shows the highest effect with IC50 value 3.6 MUM, followed by compounds 9, 5a, 8, 5e, 6e, 5b, 5f, 7a, 5c, 6c, 7b, 6a, 11, 5d and 6d. CONCLUSION: A simple and efficient route is used for the synthesis of pyrimido[5,4-e][1,2,4]triazines and pyrazolopyrimidines. The synthesized compounds are screened for antitumor activity. PMID- 29796717 TI - The Sleep Disorder in Anti-lgLON5 Disease. AB - PURPOSE OF REVIEW: To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. RECENT FINDINGS: Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia. PMID- 29796718 TI - Monogamous Halo Effects: The Stigma of Non-Monogamy within Collective Sex Environments. PMID- 29796719 TI - Emerging Rodent-Borne Viral Zoonoses in Trento, Italy. AB - Rodent-borne hanta- and arenaviruses are an emerging public health threat in Europe; however, their circulation in human populations is usually underestimated since most infections are asymptomatic. Compared to other European countries, Italy is considered 'low risk' for these viruses, yet in the Province of Trento, two pathogenic hantaviruses (Puumala and Dobrava-Belgrade virus) and one arenavirus (Lymphocytic Choriomeningitis Virus) are known to circulate in rodent reservoirs. In this paper, we performed a follow-up serological screening in humans to detect variation in the prevalence of these three viruses compared to previous analyses carried out in 2002. We also used a statistical model to link seropositivity to risk factors such as occupational exposure, cutting firewood, hunting, collecting mushrooms, having a garden and owning a woodshed, a dog or a companion rodent. We demonstrate a significant increase in the seroprevalence of all three target viruses between 2002 and 2015, but no risk factors that we considered were significantly correlated with this increase. We conclude that the general exposure of residents in the Alps to these viruses has probably increased during the last decade. These results provide an early warning to public health authorities, and we suggest more detailed diagnostic and clinical investigations on suspected cases. PMID- 29796721 TI - The emergence and pitfalls of international tissue banking. AB - The rapid growth of tissue banking and associated international organisations following the fall of the Berlin wall in 1991 is described. This surge in collaboration led to a world-wide constructive movement to use and to produce human tissues. As the years progressed industrialisation, led by the USA, improved the quality of tissue allografts but led higher costs and consolidation within the developing industry. The growth of litigation more than kept pace with the industrial progress. One landmark case is described, the outcome of which could revolutionise the current practices now applied to eliminate possible viral contamination of implanted tissue grafts. PMID- 29796720 TI - Social information in equine movement gestalts. AB - One model of signal evolution is based on the notion that behaviours become increasingly detached from their original biological functions to obtain a communicative value. Selection may not always favour the evolution of such transitions, for instance, if signalling is costly due to predators usurping signal production. Here, we collected inertial movement sensing data recorded from multiple locations in free-ranging horses (Equus caballus), which we subjected to a machine learning algorithm to extract kinematic gestalt profiles. This yielded surprisingly rich and multi-layered sets of information. In particular, we were able to discriminate identity, breed, sex and some personality traits from the overall movement patterns of freely moving subjects. Our study suggests that, by attending to movement gestalts, domestic horses, and probably many other group-living animals, have access to rich social information passively but reliably made available by conspecifics, a finding that we discuss in relation with current signal evolution theories. PMID- 29796722 TI - Acute ecotoxicity bioassay using Dendrocephalus brasiliensis: alternative test species for monitoring of contaminants in tropical and subtropical freshwaters. AB - In International guidelines for standard ecotoxicological bioassays, Daphnia magna is the most applied microcrustacea for assessing toxicity of different pollutants. However, in research realized in tropical and subtropical areas, autochthonous species must be prioritized because they are adapted to the specificities of ecosystems. In this sense, the present study aimed to assess and compare (with D. magna) the sensitivity of the tropical species Dendrocephalus brasiliensis as alternative test species for monitoring of contaminants in tropical and subtropical freshwaters, by carrying out acute toxicity tests with different pollutants. According results, D. brasiliensis presented EC50-48 h values lower than D. magna for all substances tested, indicating higher sensitivity of the tropical organism in relation to the temperate organism. Furthermore, comparing the results obtained with data from other studies, D. brasiliensis is more sensitive to the chemicals tested than D. magna and has similar sensitivity to Pseudosida ramosa and Ceriodaphnia dubia, common species in tropical areas. In view of this, we suggest that D. brasiliensis can be used as alternative test species for monitoring of contaminants in tropical and subtropical freshwaters. PMID- 29796723 TI - Impact of surgery and radiation therapy on spinal high-grade gliomas: a population-based study. AB - INTRODUCTION: Spinal high-grade gliomas (S-HGGs) is an extremely rare entity in the literature, with only sporadic cases reported. We aim to characterize prognostic factors for post-treatment survival using the SEER database. METHODS: We examined all patients with gliomas located in the spinal cord. WHO-grade was first determined by site-specific factor-1 (WHO-grade), then supplemented by direct review of ICD-O-3 histology. Only grades 3 and 4 were included in this study. Multivariable Cox regression analysis was performed. RESULTS: A total of 158 high-grade spinal cord gliomas were included. Mean age at diagnosis was 36.88 years with 52.8% male. Median survival of all patients was 20 months. A stepwise Akaike information criterion was performed for multivariable Cox regression, with forced inclusion of surgery extent and postoperative radiation therapy (RT). The final model selection added tumor size in addition to these two variables. Tumor size was not related to survival in our study. The extend of surgery had no significant impact on survival of patients, whereas postoperative RT is associated with prolonged survival (HR = 0.55, CI [0.33, 0.93], p = 0.026). CONCLUSION: S-HGGs are rare tumors with aggressive course of disease. We have found that overall median survival of S-HGGs is poor at 24 months, and no demographic or tumor-related factors have been confirmed. Extend of surgery is not associated with improved survival after adjusting for postoperative RT. Postoperative RT is the only factor in our study associated with prolonged survival in S-HGGs. PMID- 29796725 TI - Ultrahigh-Field Quantitative MR Microscopy of the Chicken Eye In Vivo Throughout the In Ovo Period. AB - PURPOSE: Ultrahigh-field MRI (UHF-MRI) with an in-plane spatial resolution of less than 100 MUm is known as MR microscopy (MRM). MRM provides highly resolved anatomical images and allows quantitative assessment of different tissue types using diffusion-weighted imaging (DWI). The aim of the present study was to evaluate the feasibility of combined in vivo anatomical and quantitative assessment of the developing chicken eye in ovo. PROCEDURES: Thirty-eight fertilized chicken eggs were examined at 7.1 T (ClinScan, Bruker Biospin, Germany) acquiring a dataset comprising T2-weighted anatomical images, DWI, and diffusion tensor imaging. To reduce motion artifacts, the eggs were moderately cooled before and during MR imaging. Two eggs were imaged daily for the entire developmental period, and 36 eggs were examined pairwise at only one time point of the embryonic period. Development of the eye was anatomically and quantitatively assessed. RESULTS: From the D5 embryonic stage (116-124 h), MRM allowed differentiation between lens and vitreous body. The lens core and periphery were first identified at D9. DWI allowed quantification of lens maturation based on a significant decrease in apparent diffusion coefficient values and course of fractional anisotropy. Repeated moderate cooling had no influence on the development of the chicken embryo. CONCLUSIONS: MRM allows in vivo assessment of embryonic development of the chicken eye in ovo without affecting normal development. The method provides anatomical information supplemented by quantitative evaluation of lens development using DWI. With increasing availability of ultrahigh-field MR systems, this technique may provide a noninvasive complementary tool in the field of experimental ophthalmology. PMID- 29796724 TI - The clinical importance of medulloblastoma extent of resection: a systematic review. AB - BACKGROUND: Although the majority of current medulloblastoma adjuvant therapy protocols treat patients with >= 1.5 cm2 residual tumor as high risk with increased craniospinal irradiation, the true prognostic significance of extent of resection (EOR) in medulloblastoma is unknown. OBJECTIVES: We sought to synthesize the body of literature on EOR and survival to determine if a definitive association exists. DATA SOURCES/ELIGIBILITY CRITERIA: A PubMed search was conducted for the terms "medulloblastoma" combined with "extent of resection," "overall survival," "progression free survival," "gross total resection," "near total resection," "partial resection," or "subtotal resection." Studies that performed a statistical analysis of EOR and survival were included. RESULTS: Sixteen articles including 1489 patients found a statistically significant association between EOR and survival, 20 articles including 2335 patients did not find a significant association between EOR and survival, and 14 articles including 2950 patients had mixed results. The three articles that accounted for molecular subgroup found varying associations between EOR and progression free survival, while no association was found between EOR and overall survival. LIMITATIONS: This review is limited by inconsistent definitions of EOR, the retrospective nature of the articles analyzed, and infrequent use of multivariate statistical analyses. CONCLUSIONS: The prognostic importance of EOR for medulloblastoma is unclear and warrants re-evaluation, particularly in the context of molecular subgrouping. PMID- 29796726 TI - Management of Myelofibrosis-Related Cytopenias. AB - PURPOSE OF REVIEW: Cytopenias, particularly anemia, are frequently encountered in patients with myelofibrosis. Management of cytopenias in myelofibrosis can be very challenging because current therapeutic interventions are only of modest efficacy and ruxolitinib, the only approved drug for myelofibrosis, is myelosuppressive. Yet, dose optimization of ruxolitinib is important for its survival benefit in patients with advanced disease. We sought to summarize the data on treatments for cytopenias available at present and review promising agents in development and emerging strategies. RECENT FINDINGS: The activin receptor ligand traps hold considerable promise for the treatment of anemia and could represent an attractive combination strategy with ruxolitinib. Low-dose thalidomide, which could offset both anemia and thrombocytopenia caused by ruxolitinib, represents another potential partner for ruxolitinib. The anti fibrotic agent PRM-151 produced sustained improvements in cytopenias in some patients, and further data on this drug are eagerly awaited. Finally, several preclinical leads with translational potential are worthy of clinical investigation as strategies to halt/reverse bone marrow fibrosis and thereby improve cytopenias. Cytopenias remain a significant hurdle in myelofibrosis management, but several novel investigational agents hold considerable promise for the future. PMID- 29796727 TI - Impact of Vial Washing and Depyrogenation on Surface Properties and Delamination Risk of Glass Vials. AB - PURPOSE: The proper understanding of glass delamination is important to glass manufacturers, pharmaceutical companies, and health authorities to mitigate the occurrence of glass flakes from the vial when in contact with specific drug product solutions. The surface of glass vials is altered during glass cane- and vial forming processes and is exposed to different stress conditions during drug product processing before coming in contact with the drug product solution. In this study, the impact of vial washing and depyrogenation including an evaluation of various residual water volumes on surface properties of glass vials was investigated for a defined set of vials. METHODS: 3D laser scanning microscopy was established as a new method for topographic analysis of curved surfaces of glass vials operating in high-throughput mode. A subset of vials was subsequently exposed to delamination stress testing and both the stressed solution and inner vial surface were analyzed by a panel of conventional and advanced analytical techniques including 3D laser scanning microscopy. RESULTS: The data showed that vial washing and depyrogenation strongly influenced surface properties, in particular those of uncoated vials. Surface characteristics such as pits increased depending on the process conditions, which especially applies to Expansion 33 vials. Even low residual water volumes of 50 MUL after vial washing were sufficient to change the surface properties of the glass and weaken the surface in those positions prone to glass delamination. An increase in pits was related to a greater risk for glass delamination. CONCLUSIONS: Vial processing conditions need to be assessed when aiming at minimizing the glass delamination risk during parenteral product storage. PMID- 29796728 TI - Genetic study of eight Egyptian patients with pycnodysostosis: identification of novel CTSK mutations and founder effect. AB - : This is the first Egyptian study with detailed clinical and orodental evaluation of eight patients with pycnodysostosis and identification of four mutations in CTSK gene with two novel ones and a founder effect. INTRODUCTION: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia due to mutations in the CTSK gene encoding for cathepsin K, a lysosomal cysteine protease. METHODS: We report on the clinical, orodental, radiological, and molecular findings of eight patients, from seven unrelated Egyptian families with pycnodysostosis. RESULTS: All patients were offspring of consanguineous parents and presented with the typical clinical picture of the disorder including short stature, delayed closure of fontanels, hypoplastic premaxilla, obtuse mandibular angle, and drum stick terminal phalanges with dysplastic nails. Their radiological findings showed increased bone density, acro-osteolysis, and open cranial sutures. Mutational analysis of CTSK gene revealed four distinct homozygous missense mutations including two novel ones, c.164A>C (p. K55T) and c.433G>A (p.V145M). The c.164A>C (p. K55T) mutation was recurrent in three unrelated patients who also shared similar haplotype, suggesting a founder effect. CONCLUSION: Our findings expand the mutational spectrum of CTSK gene and emphasize the importance of full clinical examination of all body systems including thorough orodental evaluation in patients with pycnodysostosis. PMID- 29796729 TI - Analysis of Potential Alterations Affecting SETBP1 as a Novel Contributing Mechanism to Inhibit PP2A in Colorectal Cancer Patients. AB - BACKGROUND: The functional loss of the tumor suppressor protein phosphatase 2A (PP2A) occurs in a wide variety of human cancers including colorectal cancer (CRC), and SET overexpression has been reported as a key contributing mechanism to inhibit PP2A. Although SET binding protein 1 (SETBP1) overexpression and gain of function mutations have been described in several hematological malignancies as common events that increase the expression levels of the PP2A inhibitor SET, thereby leading to PP2A inactivation, the potential existence of SETBP1 alterations in CRC still remains unexplored. METHODS: We studied the expression profile of SETBP1 by Western blot in a set of CRC cell lines and patient samples. Moreover, we performed co-immunoprecipitation assays to analyze the formation of the previously reported SETBP1-SET-PP2A inhibitory complex. Furthermore, we evaluated the mutational status of SETBP1 by pyrosequencing assays in a cohort of 55 CRC patients with metastatic disease after the immunohistochemical characterization of SET and p-PP2A expression in this cohort. RESULTS: We found high SETBP1 expression in several CRC lines but only in two of the patients analyzed. In addition, we demonstrated the formation of the SETBP1-SET-PP2A heterotrimeric complex in CRC cells. However, we failed to detect SETBP1 mutations in any of the CRC patient samples included in the study. CONCLUSIONS: Our results suggest that SETBP1 expression is mainly similar o lower in colorectal cancer tissue compared to normal colonic mucosa. However, its overexpression is a low prevalent alteration which could contribute to inhibit PP2A in CRC through the formation of a SETBP1-SET-PP2A complex in some CRC patients. Moreover, SETBP1 mutations are, if exist, rare events in CRC patients. PMID- 29796730 TI - Simulation of the mechanical behavior of random fiber networks with different microstructure. AB - Filamentous protein networks are broadly encountered in biological systems such as cytoskeleton and extracellular matrix. Many numerical studies have been conducted to better understand the fundamental mechanisms behind the striking mechanical properties of these networks. In most of these previous numerical models, the Mikado algorithm has been used to represent the network microstructure. Here, a different algorithm is used to create random fiber networks in order to investigate possible roles of architecture on the elastic behavior of filamentous networks. In particular, random fibrous structures are generated from the growth of individual fibers from random nucleation points. We use computer simulations to determine the mechanical behavior of these networks in terms of their model parameters. The findings are presented and discussed along with the response of Mikado fiber networks. We demonstrate that these alternative networks and Mikado networks show a qualitatively similar response. Nevertheless, the overall elasticity of Mikado networks is stiffer compared to that of the networks created using the alternative algorithm. We describe the effective elasticity of both network types as a function of their line density and of the material properties of the filaments. We also characterize the ratio of bending and axial energy and discuss the behavior of these networks in terms of their fiber density distribution and coordination number. PMID- 29796732 TI - Increased nitroglycerin-mediated vasodilation in migraineurs without aura in the interictal period. AB - PURPOSE: Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found. METHODS: A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography. RESULTS: There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39 +/- 0.68 vs 3.89 +/- 0.67 mm, respectively; p = 0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94 +/- 5.72 vs 6.08 +/- 2.98%, respectively; p = 0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56 +/- 7.36 vs 14.23 +/- 7.41%, respectively; p = 0.024). CONCLUSION: We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity. PMID- 29796733 TI - A refractory hypertensive patient with fibromuscular dysplasia and multicystic dysplastic kidney. AB - The case of a 16-year-old male patient with left renal artery stenosis due to fibromuscular dysplasia (FMD) and an atrophic kidney due to a right multicystic dysplastic kidney (MCDK) who presented with refractory hypertension is reported. On continuous Doppler imaging, the peak systolic velocity (PSV) at the stenotic site of the left renal artery was 404 cm/s. The FMD formed a "string-of-beads" appearance on computed tomographic angiography (CTA) and renal artery angiography. Percutaneous transluminal renal angioplasty (PTRA) with a balloon catheter was performed, after which the left renal artery returned to near normal, and his blood pressure decreased to within the normal range. In this case, the main cause of refractory hypertension was considered to have been renal artery stenosis due to left FMD. PMID- 29796731 TI - Sexual activity after spine surgery: a systematic review. AB - INTRODUCTION: Sexual function is an important determinant of quality of life, and factors such as surgical approach, performance of fusion, neurological function and residual pain can affect it after spine surgery. Our aim was to perform a systematic review to collate evidence regarding the impact of spine surgery on sexual function. METHODS: A systematic review of studies reporting measures of sexual function, and incidence of adverse sexual outcomes (retrograde ejaculation) after major spine surgery was done, regardless of spinal location. Pubmed (MEDLINE) and Google Scholar databases were queried using the following search words "Sex", "Sex life", "Sexual function", "Sexual activity", "retrograde ejaculation", "Spine", "Spine surgery", "Lumbar surgery", "Lumbar fusion", "cervical spine", "cervical fusion", "Spinal deformity", "scoliosis" and "Decompression". All articles published between 1997 and 2017 were retrieved from the database. A total of 81 studies were included in the final review. RESULTS: Majority of the studies were retrospective case series and were low quality (Level IV) in evidence. Anterior lumbar approaches were associated with a higher incidence of retrograde ejaculation, especially with the utilization of transperitoneal laparoscopic approach. There is inconclusive evidence on the preferred sexual position following fusion, and also on the impact of BMP-2 usage on retrograde ejaculation/sexual dysfunction. CONCLUSION: Despite limited evidence from high-quality articles, there is a general trend towards improvement of sexual activity and function after spine surgery. Future studies incorporating specific assessments of sexual activity will be required to address this important determinant of quality of life so that appropriate pre-operative counselling can be done by providers. These slides can be retrieved under Electronic Supplementary Material. PMID- 29796734 TI - Water bicarbonate modulates the response of the shore crab Carcinus maenas to ocean acidification. AB - Ocean acidification causes an accumulation of CO2 in marine organisms and leads to shifts in acid-base parameters. Acid-base regulation in gill breathers involves a net increase of internal bicarbonate levels through transmembrane ion exchange with the surrounding water. Successful maintenance of body fluid pH depends on the functional capacity of ion-exchange mechanisms and associated energy budget. For a detailed understanding of the dependence of acid-base regulation on water parameters, we investigated the physiological responses of the shore crab Carcinus maenas to 4 weeks of ocean acidification [OA, P(CO2)w = 1800 uatm], at variable water bicarbonate levels, paralleled by changes in water pH. Cardiovascular performance was determined together with extra-(pHe) and intracellular pH (pHi), oxygen consumption, haemolymph CO2 parameters, and ion composition. High water P(CO2) caused haemolymph P(CO2) to rise, but pHe and pHi remained constant due to increased haemolymph and cellular [HCO3-]. This process was effective even under reduced seawater pH and bicarbonate concentrations. While extracellular cation concentrations increased throughout, anion levels remained constant or decreased. Despite similar levels of haemolymph pH and ion concentrations under OA, metabolic rates, and haemolymph flow were significantly depressed by 40 and 30%, respectively, when OA was combined with reduced seawater [HCO3-] and pH. Our findings suggest an influence of water bicarbonate levels on metabolic rates as well as on correlations between blood flow and pHe. This previously unknown phenomenon should direct attention to pathways of acid-base regulation and their potential feedback on whole-animal energy demand, in relation with changing seawater carbonate parameters. PMID- 29796735 TI - Development and Evaluation of a Reverse-Entry Ion Source Orbitrap Mass Spectrometer. AB - As a step towards development of a high-resolution ion mobility mass spectrometer using the orbitrap mass analyzer platform, we describe herein a novel reverse entry ion source (REIS) coupled to the higher-energy C-trap dissociation (HCD) cell of an orbitrap mass spectrometer with extended mass range. Development of the REIS is a first step in the development of a drift tube ion mobility-orbitrap MS. The REIS approach retains the functionality of the commercial instrument ion source which permits the uninterrupted use of the instrument during development as well as performance comparisons between the two ion sources. Ubiquitin (8.5 kDa) and lipid binding to the ammonia transport channel (AmtB, 126 kDa) protein complex were used as model soluble and membrane proteins, respectively, to evaluate the performance of the REIS instrument. Mass resolution obtained with the REIS is comparable to that obtained using the commercial ion source. The charge state distributions for ubiquitin and AmtB obtained on the REIS are in agreement with previous studies which suggests that the REIS-orbitrap EMR retains native structure in the gas phase. Graphical Abstract ?. PMID- 29796736 TI - Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides. AB - Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions. Graphical Abstract ?. PMID- 29796737 TI - Mefenamic Acid Attenuates Chronic Alcohol Induced Cognitive Impairment in Zebrafish: Possible Role of Cholinergic Pathway. AB - Based on the scientific evidence supporting the neuroinflammatory response contributes the cognitive impairment associated with chronic alcoholism and the neuroprotective actions of mefenamic acid with reversal of memory loss and brain inflammation in mice, this study was designed to evaluate the effect of mefenamic acid against chronic alcohol induced cognitive impairment in zebrafish model. Zebrafish were grouped and subjected to normal behavioral analysis in light-dark chamber for 10 days. The preference to dark compartment was noted in zebrafish. Zebrafish were grouped and exposed to escalating doses of alcohol for 28 days with and without mefenamic acid exposure (100 and 200 ug/L) and subjected to a fear conditioning passive avoidance task from day 13 of 28. The cognitive evaluation was performed for 10 days and the brain tissue was isolated to estimate acetylcholinesterase activity. In cognitive evaluation study, the normal zebrafish retained the memory of the learned task and avoided the dark. The alcohol exposed zebrafish showed impairment in retaining the memory of learned task. Mefenamic acid exposed zebrafish showed a significant protection against cognitive impairment caused by alcohol and retained the memory of learned task with a significant decrease in AChE activity in brain homogenate compared to alcohol exposed zebrafish. The results of this study suggest that the memory enhancing activity of mefenamic acid might be due to activation of cholinergic transmission that has protected neuroinflammatory and neurodegenerative conditions caused by alcohol. PMID- 29796738 TI - HBV molecular epidemiology and clinical condition of immigrants living in Italy. AB - INTRODUCTION: We investigated 170 HBsAg-positive immigrants living in Italy for 1 7 years to ascertain whether they may have become infected in the host country. METHODS: Of 2032 adult immigrants interviewed, 1727 (85%) voluntarily adhered to a screening program for bloodborne or sexually transmitted infections. HBsAg was detected in 170 (9.8%) screened immigrants who completed the diagnostic, clinical and therapeutic process at the nearest clinic of infectious diseases. HBV molecular biology was performed applying a homemade technology. Phylogenetic signal of the datasets was obtained by a likelihood-mapping analysis using TreePuzzle. RESULTS: Of the 170 HBsAg-positive immigrants, 133 were inactive carriers, 29 had chronic hepatitis and 8 compensated cirrhosis. HBV genotype was identified in 109 of the 113 HBV-DNA-positive immigrants and HBV-genotype-E predominated (68.9%). Of these 109, 6 (5.5%) subjects showed an HBV genotype absent or extremely rare in their native country: HBV-genotype-E in three from Eastern Europe and in one from Sri Lanka, possibly acquired from other immigrants from sub-Saharan countries, HBV-genotype-D1 in one from Burkina Faso and one from Senegal, possibly acquired in Italy. CONCLUSION: The data suggest that immigrants may acquire HBV infection in Italy and, therefore, HBV vaccination programs should be extended to all immigrants living in Italy. PMID- 29796741 TI - Comparative study of primary and secondary closure of the surgical wound after removal of impacted mandibular third molars. AB - AIM: Aim of the study is to compare the primary and secondary healing after surgical removal of impacted mandibular third molars, in terms of swelling, severity of pain, trismus, and periodontal healing between two types of closure. MATERIALS AND METHODS: A total of 60 patients, divided into two groups randomly: group A, with 30 patients in which primary closure was done; group B, with 30 patients in which secondary closure was done. A comparison between two groups was done in terms of postoperative pain, swelling, trismus at first, third, and seventh postoperative days, and periodontal healing near adjacent second molar after 6 months. RESULTS: The swelling and pain in group A were greater than that in group B, with a statistically significant difference (p < 0.05). Mouth opening is greater in group B compared to group A. There is no significant difference in periodontal healing in between two groups after 6 months. Complication like alveolar osteitis was noted in 1 patient (3.3%) in group B. CONCLUSION: We conclude that secondary closure was better than primary closure in terms of postoperative pain, swelling, and trismus. Irrespective of any closure technique, there is no difference in terms of periodontal healing. PMID- 29796739 TI - Antibiotic stewardship and horizontal infection control are more effective than screening, isolation and eradication. AB - PURPOSE: The global rise of multidrug resistant organisms (MDROs) is of major concern since infections by these pathogens are difficult, and in some cases, even impossible to treat. This review will discuss the effectiveness of a pathogen-independent alternative approach consisting of the implementation of antibiotic stewardship (ABS) programs, improvement of hand hygiene compliance, and daily antiseptic body washings instead of "screening, isolation and eradication" as recommended by many infection control guidelines today. METHODS: A review of the literature. RESULTS: The classical approach composed of screening, isolation and eradication has many limitations, including lack of standardization of the screening methods, risk of medical errors for patients in isolation and failure to eradicate resistant bacteria. Notably, concrete evidence that this current infection control approach actually prevents transmission is still lacking. We found that a novel approach with the training of infectious diseases specialists can reduce the usage of antimicrobials, thereby significantly decreasing the emergence of new MDROs. Moreover, increased hand hygiene compliance not only reduces transmission of MDROs, but also that of sensitive organisms causing the majority of nosocomial infections. Further, instruments, such as continuing education, bed-side observation, and the use of new tools, e.g. electronic wearables and Wi-Fi-equipped dispensers, are all options that can also improve the current low hand hygiene compliance levels. In addition, daily antiseptic body washes were observed to reduce the transmission of MDROs, especially those deriving from the body surface-like MRSA and VRE in specific settings. Finally, antiseptic body washes were seen to have similar effects on reducing transmission rates as screening and isolation measures. CONCLUSIONS: In summary, this review describes a novel evidence-based approach to counteract the growing medical challenge of increasing numbers of MDROs. PMID- 29796740 TI - Treatment outcomes of hypofractionated radiotherapy combined with temozolomide followed by bevacizumab salvage therapy in glioblastoma patients aged > 75 years. AB - BACKGROUND: The optimal treatment for elderly patients with glioblastoma has not been established. METHODS: We retrospectively analyzed the safety and efficacy of hypofractionated radiotherapy (45 Gy/15 fr) combined with temozolomide (TMZ) followed by bevacizumab (BEV) salvage treatment in 18 glioblastoma patients aged > 75 years. RESULTS: All of the patients received safe hypofractionated radiotherapy and concomitant TMZ (75 mg/m2), and 14 of 18 patients received maintenance TMZ. We administered BEV to 17 of 18 patients because their Karnofsky Performance Status scores declined and/or recurrence was detected. During the follow-up period (median duration: 17.5 months, range 3-33 months), 12 patients died of their disease. While the median progression-free survival period was 2.5 months, the median overall survival period was 20 months. Adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) occurred in 5 patients. CONCLUSION: Hypofractionated radiotherapy combined with TMZ and BEV salvage treatment was found to be safe and effective in glioblastoma patients aged > 75 years. PMID- 29796742 TI - Nasal silicone splints and quilting sutures using a septum stitch device following septoplasty: a prospective comparative study. AB - PURPOSE: Although nasal splints and trans-septal sutures are preferred for septal closure following septoplasty, quilting sutures, also known as continuous mattress sutures, are technically challenging and thus time consuming. Recently, the utility of a novel stitch device was demonstrated for quilting sutures; however, whether it contributes to the technical solution and time management of septal sutures remains unclear. This study aims to quantify the time and cost of septal closure following septoplasty by comparing nasal splints with quilting sutures using the septum stitch device. METHODS: We prospectively examined 23 patients who underwent septoplasty and assigned them to the following two groups: group 1, underwent the quilting suture for septal closure following septoplasty; group 2 underwent the nasal silicone splint method. We recorded the total operation time and surgical time for septal closure. Furthermore, we evaluated postoperative symptoms with Visual Analogue Scale (VAS) scores and compared the complication rate. RESULTS: We observed no significant difference in the average of total operating time (P = 0.641) and the surgical time for septal closure (P = 0.886). Among postoperative symptoms, only nasal bleeding was significantly worse in group 1 on postoperative day 1 (P = 0.023). In addition, the occurrence of postoperative complications was insignificant between both groups. CONCLUSIONS: The septum stitch facilitated safe and easy quilting suturing without significant increase of operation time. PMID- 29796744 TI - 3D genome and its disorganization in diseases. AB - The chromosomes in eukaryotic cells are highly folded and organized to form dynamic three-dimensional (3D) structures. In recent years, many technologies including chromosome conformation capture (3C) and 3C-based technologies (Hi-C, ChIA-PET) have been developed to investigate the 3D structure of chromosomes. These technologies are enabling research on how gene regulatory events are affected by the 3D genome structure, which is increasingly implicated in the regulation of gene expression and cellular functions. Importantly, many diseases are associated with genetic variations, most of which are located in non-coding regions. However, it is difficult to determine the mechanisms by which these variations lead to diseases. With 3D genome technologies, we can now better determine the consequences of non-coding genome alterations via their impact on chromatin interactions and structures in cancer and other diseases. In this review, we introduce the various 3D genome technologies, with a focus on their application to cancer and disease research, as well as future developments to extend their utility. PMID- 29796743 TI - Soft palate cephalometric changes with a mandibular advancement device may be associated with polysomnographic improvement in obstructive sleep apnea. AB - PURPOSE: It is unclear whether soft palate-associated changes in cephalometry associated with a mandibular advancement device (MAD) are independently associated with improvements in polysomnography (PSG) respiratory parameters in obstructive sleep apnea (OSA). METHODS: This retrospective review aimed to identify the association between soft palate-associated changes in cephalometry and PSG changes after application of an MAD. Korean patients diagnosed with OSA who underwent cephalometry with or without an MAD were enrolled. All the patients were evaluated after undergoing full-night PSG twice: once with an MAD and once without. Cephalometric findings were measured using an image analyzer. RESULTS: Mean apnea-hypopnea index significantly decreased with an MAD from 36.4/h to 14.7/h (p < 0.001). Retropalatal airway space significantly increased with an MAD from 6.6 to 7.3 mm (p = 0.013). Soft palate length also significantly decreased with an MAD from 43.6 to 42.3 mm (p = 0.02). Although these findings were shown by responders (patients with a reduction of apnea-hypopnea index by more than 50%), there were no significant changes in non-responders. However, retroglossal airway space did not significantly increase with an MAD even in responders. CONCLUSIONS: Improvement of OSA with an MAD can be predicted with soft palate associated upper airway changes shown in cephalometry. PMID- 29796745 TI - Is a constant low-entropy process at the root of glycolytic oscillations? AB - We measured temporal oscillations in thermodynamic variables such as temperature, heat flux, and cellular volume in suspensions of non-dividing yeast cells which exhibit temporal glycolytic oscillations. Oscillations in these variables have the same frequency as oscillations in the activity of intracellular metabolites, suggesting strong coupling between them. These results can be interpreted in light of a recently proposed theoretical formalism in which isentropic thermodynamic systems can display coupled oscillations in all extensive and intensive variables, reminiscent of adiabatic waves. This interpretation suggests that oscillations may be a consequence of the requirement of living cells for a constant low-entropy state while simultaneously performing biochemical transformations, i.e., remaining metabolically active. This hypothesis, which is in line with the view of the cellular interior as a highly structured and near equilibrium system where energy inputs can be low and sustain regular oscillatory regimes, calls into question the notion that metabolic processes are essentially dissipative. PMID- 29796749 TI - Lethal carbon monoxide toxicity in a concrete shower unit. AB - A 47-year-old previously-well woman was found dead on the floor of a shower cubicle on a property in rural South Australia. The impression of the attending doctor and police was of collapse due to natural disease. Although there was significant stenosing coronary artery atherosclerosis found at autopsy, cherry pink discoloration of tissues prompted measurement of the blood carboxyhemoglobin level which was found to be 55%. The source of the gas was a poorly-maintained hot water heater that was mounted on the inside wall of the shower. Construction of the shower using an impermeable concrete rain water tank had caused gas accumulation when the water heater malfunctioned. Had lethal carbon monoxide exposure not been identified others using the same shower unit would also have been at risk. PMID- 29796748 TI - Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes. AB - AIMS/HYPOTHESIS: Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. METHODS: We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. RESULTS: Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/-SD) of 6.4 +/- 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF) 23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. CONCLUSIONS/INTERPRETATION: We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event. PMID- 29796746 TI - HRP-mediated graft polymerization of acrylic acid onto silk fibroins and in situ biomimetic mineralization. AB - Silk fibroin (SF) can be extensively utilized in biomedical areas owing to its appreciable bioactivity. In this study, biocompatible composites of SF and hydroxyapatite (HAp) were fabricated through in situ biomimetic mineralization process. Graft copolymerization of acrylic acid (AA) onto SF was conducted by using the catalytic system of acetylacetone (ACAC), hydrogen peroxide (H2O2) and horseradish peroxidase (HRP), for enhancing the deposition of apatite onto the fibroin chains. Subsequently, biomimetic mineralization of the prepared fibroin based membrane was performed in Ca/P solutions to synthesize the organized SF/HAp composites. The efficacies of graft copolymerization and biomimetic mineralization were evaluated by means of ATR-FTIR, GPC, EDS-Mapping, XRD and others. The results denoted that AA was successfully graft-copolymerized with fibroin and formed the copolymer of silk fibroin-graft-polyacrylic acid (SF-g PAA), and the grafting percentage (GP) and grafting efficiency (GE) under the optimal condition reached to 23.2% and 29.4%, respectively. More mineral phases were detected on the surface of SF-g-PAA membrane after mineralization process when compared to that of the untreated fibroin membrane, companying with an improved mechanical property. According to MG-63 cell viability and fluorescent adhesion assays, the mineralized SF-g-PAA composite showed satisfactory biocompatibility and exceptional adhesive effects as well. The synthetized composite of SF-g-PAA/HAp can be potentially applied in the fields of bone tissue engineering. PMID- 29796750 TI - Does cognition improve following LVAD implantation? AB - BACKGROUND: Studies of cognition after LVAD surgery have produced mixed results. To explore whether cognition would improve, decline, or remain stable after LVAD surgery, we examined cognition before and 1- and 3-months after LVAD surgery. Patients with post-surgical stroke were excluded. METHODS: 28 subjects (mean age = 54.31 +/- 12 years) comprised an observational case series from the DuraHeart LVAS device(r) trial. Cognitive testing was performed at baseline, 1-month, and 3 month post-surgery, and included tests of attention, memory, language, visualmotor speed (TMT) and visualconstruction. RESULTS: No difference in cognition was found between baseline and 1-month exams (means z score improvement = 0.06, p = 0.43) but cognition improved significantly between baseline and 3 month exams (mean z score improvement = 0.34, p < 0.00001). Examination of individual test scores found, after correction for multiple comparisons, only the TMT variable was significantly different at the 3-month exam. CONCLUSIONS: We found significantly improved cognition 3 months after LVAD surgery in a subset of patients without post-surgical stroke. The reasons for the lack of cognitive improvement at the 1-month post-surgical assessment may include ongoing medical and physiological disruptions in the immediate post-operative period. Further research into the sources of delayed improvement is warranted. Cognitive assessments performed immediately after surgery should be interpreted with caution because the results may not reflect longer term cognitive outcomes. LVAD patients may require additional support to successfully manage their health in the weeks immediately following surgery but assistance needs may decrease over time. PMID- 29796751 TI - Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients. AB - OBJECTIVES: The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes. METHODS: We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: "early" if less than 3 days or "late" if 3 or more days after lung transplantation. RESULTS: Forty-nine patients (51%) underwent tracheostomy 3.2 +/- 1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p = 0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p = 0.003) and oral feeding (p = 0.0006) earlier and had a shorter duration of mechanical ventilation (p = 0.04) and shorter length of intensive care unit (p = 0.01) and hospital stay (p = 0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p = 0.06), oral feeding (p = 0.17), or length of hospital stay (p = 0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy. CONCLUSIONS: Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation. PMID- 29796753 TI - An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis. AB - PURPOSE: Intraventricular hemorrhage (IVH) affects approximately 50% of premature births where 50% further develop post-hemorrhagic ventricular dilation (PHVD). Patients face significant impact to long-term development if PHVD is not managed. Unfortunately, there is no accepted treatment to remove the thrombus caused by IVH. This paper describes an acute and chronic IVH model for use with magnetic resonance-guided focused ultrasound (MRgFUS) thrombolysis. METHODS: A total of 12 pigs (~ 1 month in age) were used in the model (eight acute and four chronic). A pre-operative brain MRI was obtained for ventricular targeting. 1.25 cm3/kg of autologous blood was injected through a burr hole lateral to the midline and anterior of the coronal suture at a rate of 0.6 cm3/min. A craniotomy was performed to simulate a "fontanelle". Post-operative MRI was used to calculate the clot volume. Chronic piglets were recovered, monitored daily with a neurological scoring system (NSS), and MRI scanned for 21 days. RESULTS: The clot injection was well tolerated. The average clot size was 3987 mm3 (median = 4330 mm, standard deviation = 739 mm3). Postmortem examination validated the presence of the clot. In the chronic animals, there was an increase in ventricular volume of 30%. Transient neurological impairment immediately followed clot injection and with onset of hydrocephalus in the chronic animals. CONCLUSIONS: This model establishes a measurable and targetable IVH clot in an MRI-based neonatal porcine model. The progressive post-hemorrhagic ventricular dilation in the chronic model is a potential alterable outcome from MRgFUS thrombolysis. PMID- 29796754 TI - Clinical characteristics and ocular complications of patients with scleritis in Japanese. AB - PURPOSE: To investigate the clinical characteristics of Japanese patients with scleritis STUDY DESIGN: Retrospective study METHODS: The clinical records of 123 patients with scleritis, who presented to the University of Tokyo Hospital between January, 2004 and December, 2015, were retrospectively reviewed. RESULTS: The cohort comprised 55 men and 68 women (mean age, 57.8+/-16.4 years), of which 76 showed anterior diffuse scleritis, 17 showed anterior nodular scleritis, 10 showed anterior necrotizing scleritis, and 20 showed posterior scleritis. The underlying etiology was identified in 39 patients. Autoimmune diseases were present in 32 patients, including eight with rheumatoid arthritis, seven with antineutrophil cytoplasmic antibody-associated vascular disease, and six with relapsing polychondritis. Ocular hypertension was the most common ocular complication (41%), followed by anterior chamber cells (38%). Fifty-three percent of patients required systemic immunosuppressive medication. Systemic corticosteroids were the most commonly used medication (45%), followed by methotrexate (11%). A, decrease in vision was observed in one-third of patients with anterior necrotizing scleritis or posterior scleritis, of which secondary glaucoma and optic neuritis were the major causes. CONCLUSION: Autoimmune diseases were present in 26% of patients. One-third of patients with anterior necrotizing scleritis or posterior scleritis experienced decreased vision, mostly due to secondary glaucoma and optic neuritis. Therefore, controlling intraocular pressure by methods such as administration of steroid-sparing immunosuppressive medication and appropriate treatment for posterior scleritis are essential for scleritis treatment. PMID- 29796756 TI - Purse-string rupture: pitfalls of transanal total mesorectal excision (Cecil approach). PMID- 29796755 TI - How does ageing affect grasp adaptation to a visual-haptic size conflict? AB - Previous research suggests that the ability to adapt motor behaviour to sudden environmental changes may be impaired in older adults. Here, we investigated whether the adaptation of grasping behaviour in response to a visual-haptic size conflict is also affected by increasing age. 30 older and 18 young adults were instructed to grasp a hidden block whilst viewing a second block in a congruent position. Initially block sizes were equal, but after a set number of trials a sensory conflict was introduced by covertly changing the hidden block for a smaller or larger block. The scale and speed of maximum grasp aperture adaptation to the increase or decrease in the size of the hidden block was measured. Older adults successfully adapted to the visual-haptic size conflict in a similar manner to young adults, despite a tendency to adapt less when the hidden block increased in size. This finding is attributed to the physical capabilities of the grasping hand of older adults, rather than an effect of age-related sensory or cognitive decline. The speed of grasp adaptation did not differ between age groups; however, awareness of the visual-haptic conflict lead to faster adaptation. These findings suggest that sensorimotor adaptation for grasping is intact for cognitively healthy older adults. PMID- 29796758 TI - Marked Succession of Cyanobacterial Communities Following Glacier Retreat in the High Arctic. AB - Cyanobacteria are important colonizers of recently deglaciated proglacial soil but an in-depth investigation of cyanobacterial succession following glacier retreat has not yet been carried out. Here, we report on the successional trajectories of cyanobacterial communities in biological soil crusts (BSCs) along a 100-year deglaciation gradient in three glacier forefields in central Svalbard, High Arctic. Distance from the glacier terminus was used as a proxy for soil age (years since deglaciation), and cyanobacterial abundance and community composition were evaluated by epifluorescence microscopy and pyrosequencing of partial 16S rRNA gene sequences, respectively. Succession was characterized by a decrease in phylotype richness and a marked shift in community structure, resulting in a clear separation between early (10-20 years since deglaciation), mid (30-50 years), and late (80-100 years) communities. Changes in cyanobacterial community structure were mainly connected with soil age and associated shifts in soil chemical composition (mainly moisture, SOC, SMN, K, and Na concentrations). Phylotypes associated with early communities were related either to potentially novel lineages (< 97.5% similar to sequences currently available in GenBank) or lineages predominantly restricted to polar and alpine biotopes, suggesting that the initial colonization of proglacial soil is accomplished by cyanobacteria transported from nearby glacial environments. Late communities, on the other hand, included more widely distributed genotypes, which appear to establish only after the microenvironment has been modified by the pioneering taxa. PMID- 29796757 TI - Estrogen Receptor-alpha Correlates with Higher Fungal Cell Number in Oral Paracoccidioidomycosis in Women. AB - BACKGROUND: Paracoccidioidomycosis is a neglected tropical fungal infection with great predilection for adult men, indicating the participation of female hormone estrogen in preventing paracoccidioidomycosis development in women. Estrogen has an immunologic effect leading to polarization toward the Th2 immune response, which favors the disease evolution. OBJECTIVES: To evaluate estrogen and progesterone receptors in oral paracoccidioidomycosis lesions and to verify any association with tissue fungi counting in women and men. METHODS: Thirty-two cases of chronic oral paracoccidioidomycosis were included. Immunohistochemical analyses for anti-estrogen receptor-alpha, anti-progesterone receptor and anti Paracoccidioides brasiliensis antibodies were performed. The differences between women and men and the relations among the immunomarkers for each gender were also evaluated. RESULTS: A significant positive correlation was observed between estrogen receptor-alpha and the amount of fungi in women. In addition, estrogen receptor-alpha was mildly expressed in the inflammatory cells of female patients, while progesterone receptor was expressed in both genders, with similar expression between women and men. Moreover, fungi counting revealed no differences between genders. CONCLUSIONS: Estrogen receptor-alpha was expressed only in women and showed a positive correlation with the amount of fungi in oral paracoccidioidomycosis, while progesterone receptor was observed in both genders and exhibited no correlation with estrogen receptor-alpha or fungi counting. PMID- 29796760 TI - True vs. pseudo-electrical ventricular alternans sustained by ventricular premature complexes. AB - This report describes a form of electrical ventricular alternans sustained by ventricular premature complexes (VPC). Alternans was associated with a constant heart rate (RR interval) and was therefore considered to be either a form of classic or true alternans or a mimic of the configuration seen in true alternans from other causes. In contrast, VPC-induced pseudo-alternans is characterized by an inconstant heart rate (RR interval). It is surprising that the incidence of true VPC-induced alternans is unappreciated and virtually unreported, most probably since the measurement of the RR intervals involving late VPCs is ignored. PMID- 29796761 TI - Treatment of Intracerebral Lesions with Abatacept in a CTLA4-Haploinsufficient Patient. PMID- 29796759 TI - An E. coli biosensor for screening of cDNA libraries for isochorismate pyruvate lyase-encoding cDNAs. AB - Salicylic acid (SA) is an essential hormone for development and induced defense against biotrophic pathogens in plants. The formation of SA mainly derives from chorismate via demonstrated isochorismate synthase (ICS) and presumed isochorismate pyruvate lyase (IPL)-mediated steps in Arabidopsis thaliana, but so far no plant enzyme displaying IPL activity has been identified. Here, we developed an E. coli SA biosensor to screen for IPL activity based on the SalR regulator/salA promoter combination from Acinetobacter sp ADP1, to control the expression of the reporter luxCDABE. The biosensor was responsive to micromolar concentrations of exogenous SA, and to endogenous SA produced after transformation with a plasmid permitting IPTG-inducible expression of bacterial IPL in this biosensor strain. After screening a cDNA library constructed from turnip crinkle virus (TCV)-infected Arabidopsis ecotype Di-17, we identified an enzyme, PRXR1, as a putative IPL that converts isochorismate into SA. Our results provide a new experimental approach to identify IPL and new insights into the SA biosynthesis pathway in Arabidopsis. PMID- 29796762 TI - Comparative functional outcomes of patients with adhesive capsulitis receiving intra-articular versus sub-acromial steroid injections: case-control study. AB - PURPOSE: This is a prospective case-control study comparing short- and medium term outcomes between sub-acromial and gleno-humeral corticosteroid injections in adhesive capsulitis. METHODS: The study population consisted of 105 patients (33 males, 72 females; mean age, 56.1 years). They were divided into three groups: (1) patients receiving 40 mg of methylprednisolone acetate as intra-articular injection (n = 35) followed by physical therapy; (2) patients receiving 40 mg of methylprednisolone acetate as sub-acromial injection (n = 35) followed by physical therapy; (3) patients receiving only physical therapy (heat, passive stretching exercises and wall climbing) and no injections (n = 35). Functional outcome scores (Constant shoulder score and Shoulder Pain and Disability Index), visual analogue scale for pain and range of motion of shoulder joint were noted at 3, 6 and 12 weeks and 6 months. RESULTS: There was a statistically significant improvement in VAS scores in group 1 and 2 at 3, 6, 12 weeks and 6 months compared to that before the injections. There was no statistically significant improvement in the group 3 at 3 and 6 weeks, but improvement was noticed at 12 weeks and 6 months. There was no statistically significant difference in VAS, CS score, SPADI and ROM between groups 1 and 2 at 3, 6, 12 weeks and 6 months. These scores were significantly better in group 1 and 2 compared to group 3 at 3, 6, 12, weeks and 6 months. CONCLUSIONS: Corticosteroid injections into the sub acromial space and into the gleno-humeral joint produce similar results in terms of pain relief and improvement in function in patients with adhesive capsulitis. PMID- 29796763 TI - Soft tissue tension is four times lower in the unstable primary total hip arthroplasty: does this comparison make sense? PMID- 29796764 TI - History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair? AB - PURPOSE: Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered. The aim of this technology is to halt or reverse progression of the disease to collapse. MATERIAL AND METHODS: The pioneering report by Hernigou published in 2002 was the first pilot study suggesting that injection of bone marrow stem cells was a safe approach able to improve osteonecrosis in patients with early stages. Since then, an impressive number of studies and trials employing unselected BM-derived cells (1000 the last 2 years) showed that delivery of those cells to the site of osteonecrosis during core decompression was somehow able to ameliorate the patient with osteonecrosis. In order to translate the promise of this cell therapy into better clinical benefit, many questions need to be addressed. In this review, we therefore analyzed current clinical experience of the literature and our experience of 4000 cases to address these questions and particularly the number of cells that should be injected. RESULTS: After almost 20 years of clinical research in this field, we are still far from having drawn conclusions on the number of cells we should inject in regenerating hip osteonecrosis. Findings are difficult to interpret due to heterogeneity of causes of osteonecrosis, as well as differences in the cells count, sample quality, and stages of osteonecrosis. The authors address specific issues, as cell quality, cell numbers, volume of osteonecrosis, concentration of cells, and ex vivo expansion. Bone marrow mesenchymal stem cells are supposed to be "functionally competent," but are collected from the bon, marrow of patients with diseases and risk factors of osteonecrosis. The recipient organ (bone osteonecrosis) is a tissue where several alterations have already occurred. These questions are addressed in this review. CONCLUSION: In this review, we analyzed current clinical experience regarding cell therapy and address issues that should be a guide for future cell-based therapeutic application in osteonecrosis. PMID- 29796767 TI - ? PMID- 29796766 TI - [Another "War on Drugs" : A war against addicts and a "roll-back" for patients needing opioids?] PMID- 29796765 TI - Escherichia coli modular coculture system for resveratrol glucosides production. AB - In bio-based fermentation, the overall bioprocess efficiency is significantly affected by the metabolic burden associated with the expression of complete biosynthetic pathway as well as precursor and cofactor generating enzymes into a single microbial cell. To attenuate such burden by compartmentalizing the enzyme expression, recently synthetic biologists have used coculture or poly-culture techniques for biomolecules synthesis. In this paper, coculture system of two metabolically engineered Escherichia coli populations were employed which comprises upstream module expressing two enzymes converting para-coumaric acid into resveratrol and the downstream module expressing glucosyltransferase to convert the resveratrol into its glucosidated forms; polydatin and resveratroloside. Upon optimization of the initial inoculum ratio of two E. coli populations, 92 mg resveratrol glucosides/L (236 uM) was produced i.e. achieving 84% bioconversion from 280 uM of p-coumaric acid in 60 h by 3 L fed batch fermentor. This is the report of applying coculture system to produce resveratrol glucosides by expressing the aglycone formation pathway and sugar dependent pathway into two different cells. PMID- 29796770 TI - Correction to: Accuracy of genomic selection to predict maize single-crosses obtained through different mating designs. AB - Unfortunately, the first author name of the above-mentioned article was incorrectly published in the original publication. The complete correct name should read as follows. PMID- 29796769 TI - Properties of collagen-based hemostatic patch compared to oxidized cellulose based patch. AB - Two self-adhering hemostatic patches, based on either PEG-coated collagen (PCC) or PEG-coated oxidized cellulose (PCOC), are compared regarding to maximum burst pressure, mechanical stability, and swelling. In addition, the induction of tissue adhesions by the materials was assessed in a rabbit liver abrasion model. Both materials showed comparable sealing efficacy in a burst pressure test (37 +/ 16 vs. 35 +/- 8 mmHg, P = 0.730). After incubation in human plasma, PCC retained its mechanical properties over the test period of 8 h, while PCOC showed faster degradation after the 2 h time-point. The degradation led to a significantly decreased force at break (minimum force at break 0.55 N during 8 h for PCC, 0.27 N for PCOC; p < 0.001). Further, PCC allowed significantly higher deformation before break (52% after 4 h and 50% after 8 h for PCC, 18% after 4 h and 23% after 8 h for PCOC; p = 0.003 and p < 0.001 for 4 h and 8 h, respectively) and showed less swelling in human plasma (maximum increase in thickness: ~20% PCC, ~100% PCOC). Faster degradation of PCOC was visible macroscopically and histologically in vivo after 14 days. PCC showed visible structural residues with little cellular infiltration while strong infiltration with no remaining structural material was seen with PCOC. In vivo, a higher incidence of adhesion formation after PCOC application was detected. In conclusion, PCC has more reliable mechanical properties, reduced swelling, and less adhesion formation than PCOC. PCC may offer greater clinical benefit for surgeons in procedures that have potential risk for body fluid leakage or that require prolonged mechanical stability. PMID- 29796772 TI - Abdominal lymphatic malformations. AB - BACKGROUND: Abdominal lymphatic malformations (LM) are relatively rare findings in the differential diagnosis of focal abdominal lesions; however, they represent a challenge especially in younger patients. The aim of this review article is to provide up-to-date information about the different kinds of LM manifestations. In addition, related syndromes and typical imaging features to facilitate the diagnosis are discussed. RESULTS: The clinical presentation of abdominal LM is unspecific, whereby most are asymptomatic and comprise incidental findings of thin-walled cystic masses anywhere in the abdomen. The fluid in the cystic masses may be proteinaceous, contain blood, or be infected. Radiological imaging features overlap with other cystic diseases; hallmark in LM is a lack of a solid component and exclusive enhancement of the walls and septa. CONCLUSION: In cystic abdominal masses in early childhood or young adults, abdominal LM must be taken into account by the radiologist. Newly defined entities in this spectrum of diseases are central conducting lymphatic anomaly (CCLA) and generalized lymphatic anomaly (GLA). PMID- 29796773 TI - Bilateral Bow Hunter's Syndrome Mimicking a Classic Seizure Semiology. PMID- 29796771 TI - Green Synthesis of Metal and Metal Oxide Nanoparticles and Their Effect on the Unicellular Alga Chlamydomonas reinhardtii. AB - Recently, the green synthesis of metal nanoparticles has attracted wide attention due to its feasibility and very low environmental impact. This approach was applied in this study to synthesise nanoscale gold (Au), platinum (Pt), palladium (Pd), silver (Ag) and copper oxide (CuO) materials in simple aqueous media using the natural polymer gum karaya as a reducing and stabilising agent. The nanoparticles' (NPs) zeta-potential, stability and size were characterised by Zetasizer Nano, UV-Vis spectroscopy and by electron microscopy. Moreover, the biological effect of the NPs (concentration range 1.0-20.0 mg/L) on a unicellular green alga (Chlamydomonas reinhardtii) was investigated by assessing algal growth, membrane integrity, oxidative stress, chlorophyll (Chl) fluorescence and photosystem II photosynthetic efficiency. The resulting NPs had a mean size of 42 (Au), 12 (Pt), 1.5 (Pd), 5 (Ag) and 180 (CuO) nm and showed high stability over 6 months. At concentrations of 5 mg/L, Au and Pt NPs only slightly reduced algal growth, while Pd, Ag and CuO NPs completely inhibited growth. Ag, Pd and CuO NPs showed strong biocidal properties and can be used for algae prevention in swimming pools (CuO) or in other antimicrobial applications (Pd, Ag), whereas Au and Pt lack these properties and can be ranked as harmless to green alga. PMID- 29796768 TI - [Pain and epilepsy : A clinical, neuroanatomical and pathophysiological review]. AB - Besides postictal headaches, epileptic seizures are infrequently associated with pain experiences. Nevertheless, seizure-associated pain is an important clinical symptom to recognize, diagnose and to differentiate from non-epileptic disorders. Seizure-associated pain may shed light on the anatomical and pathophysiological foundation of pain in general. According to its localization seizure-related pain is classified as unilateral somatosensory, abdominal and cephalic epileptic pain and according to its temporal relationship as ictal, peri-ictal, and interictal pain. Different aspects of pain phenomena in the context of epileptic seizures will be addressed by following these systematic classifications. In relation to seizures with unilateral somatosensory manifestation the functional anatomical context is described while differential diagnostic aspects in association with abdominal epilepsies are emphasized and terminological points as well as genetic epidemiological interrelationships between epilepsy and migraine are highlighted. PMID- 29796774 TI - Polymicrobial interactions influence the agr copy number in Staphylococcus aureus isolates from diabetic foot ulcers. AB - Diabetic foot ulcers are a major complication of diabetes and are often colonised by complex bacterial communities, where Staphylococcus aureus is frequently co present with Pseudomonas aeruginosa. These bacteria interact through quorum sensing, encoded in S. aureus by the accessory gene regulator (agr). Typing and copy number of S. aureus agr were assessed here to give insights on strain variability and possible interspecies influence. As agr is classified in four genetic groups, agr-I, agr-II, agr-III and agr-IV, the agr type of 23 S. aureus diabetic foot ulcers isolates was evaluated by PCR and gene copy number determined by qPCR, including in S. aureus present in polymicrobial infections. agr-I and agr-II were found to be present in 52 and 39% of the isolates, respectively. In two isolates, no agr type was identified, and types III and IV were not detected. Interestingly, agr-II copy number was higher in dual suspensions than in S. aureus single suspension. We conclude that agr type I was the most frequent in clinical centers in Lisbon, and variations in agr-I and agr II copy numbers were strain specific. Variations in agr copy number in dual suspensions suggests that P. aeruginosa may influence S. aureus agr-II gene regulation, confirming an interaction between these two bacteria. This is a first approach to characterise agr variation in S. aureus from diabetic foot ulcers in vitro. PMID- 29796775 TI - The prevalence and risk factors of nocturia in China, South Korea, and Taiwan: results from a cross-sectional, population-based study. AB - PURPOSE: To examine the prevalence, symptomatology, and risk factors for nocturia using data from an internet-based questionnaire conducted in China, South Korea, and Taiwan. METHODS: Data from a cross-sectional, population-representative, internet-based study conducted among men and women aged >= 40 years were analysed post hoc. Nocturia prevalence and bother were analysed by sex and age group, and with regard to comorbid conditions and lower urinary tract symptoms (LUTS). Multivariate and univariate logistic regression models to identify risk factors for nocturia were constructed, with nocturia involving >= 2 nocturnal voids as the dependent variable. RESULTS: Among the 8284 participants, the prevalence of nocturia involving >= 1, >= 2, or >= 3 voids was slightly higher for women (76.1, 37.3, and 17.5%, respectively) compared with men (74.0, 34.5, and 15.5%, respectively). The prevalence and associated bother of nocturia increased with age. Greater proportions of patients with comorbid conditions or wet/more severe overactive bladder syndrome (OAB) experienced nocturia than those without. Multivariate analysis identified that female sex, age > 60 years, diabetes, cardiac disease, body mass index, International Prostate Symptom Score (IPSS) voiding score, stress urinary incontinence, wet OAB, and Hospital Anxiety And Depression Scale (HADS) anxiety score were associated with >= 2 nocturnal voids. Hypertension was associated with >= 2 nocturnal voids in women but not men, and alcohol consumption in men but not women. CONCLUSIONS: Nocturia is a common and bothersome condition affecting a large proportion of men and women aged >= 40 years in China, South Korea, and Taiwan. Factors associated with nocturia included age, sex, comorbid conditions, and LUTS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT02618421. PMID- 29796776 TI - Role of dihydroartemisinin in regulating prostaglandin E2 synthesis cascade and inflammation in endothelial cells. AB - Endothelial cells (ECs) are crucial in maintaining vascular homeostasis. Endothelial dysfunction was involved in many cardiovascular diseases (CVDs). Recently, antimalarial medicine artemisinin and its derivatives including dihydroartemisinin (DHA) were found to be beneficial in some diseases including CVDs. Prostaglandin (PG) E2 is a known inflammatory mediator and plays important roles in cardiovascular system. This study was to investigate the role of DHA in regulating cyclooxygenase (COX)/PGE synthase (PGES)/PGE2 cascade and inflammation in ECs. After DHA treatment, the mRNA and protein levels of COX-2 were strikingly upregulated in time- and dose-dependent manners. In contrast, COX-1 was significantly downregulated. As expected, inhibition of COX-1 or COX-2 further reduced PGE2 production after DHA treatment. Moreover, DHA enhanced microsomal PGE2 synthase (mPGES)-2 and moderately modulated cytosolic PGE2 synthase (cPGES) with no effect on mPGES-1 expression. Importantly, DHA significantly reduced PGE2 levels in line with the upregulation of 15-hydroxyprostaglandin dehydrogenase (15 PGDH, a key enzyme for prostaglandin degradation). Lastly, we observed that DHA not only reduced the PGE2 levels in tumor necrosis factor-alpha (TNF-alpha) treated ECs but also blunted the upregulation of inflammatory cytokines of interleukin (IL)-6 and IL-1beta induced by TNF-alpha or PGE2. These findings demonstrated an important role of DHA in regulating PGE2 synthesis cascade and inflammation in ECs, suggesting a potential of DHA for the treatment of inflammatory vascular diseases. PMID- 29796777 TI - Catechol neurochemistry in the autonomic clinic: helpful but not absolutely required. PMID- 29796778 TI - Putting hands to rest: efficient deep CNN-RNN architecture for chemical named entity recognition with no hand-crafted rules. AB - Chemical named entity recognition (NER) is an active field of research in biomedical natural language processing. To facilitate the development of new and superior chemical NER systems, BioCreative released the CHEMDNER corpus, an extensive dataset of diverse manually annotated chemical entities. Most of the systems trained on the corpus rely on complicated hand-crafted rules or curated databases for data preprocessing, feature extraction and output post-processing, though modern machine learning algorithms, such as deep neural networks, can automatically design the rules with little to none human intervention. Here we explored this approach by experimenting with various deep learning architectures for targeted tokenisation and named entity recognition. Our final model, based on a combination of convolutional and stateful recurrent neural networks with attention-like loops and hybrid word- and character-level embeddings, reaches near human-level performance on the testing dataset with no manually asserted rules. To make our model easily accessible for standalone use and integration in third-party software, we've developed a Python package with a minimalistic user interface. PMID- 29796779 TI - Omics Approaches in Sleep-Wake Regulation. AB - Although sleep seems an obvious and simple behaviour, it is extremely complex involving numerous interactions both at the neuronal and the molecular levels. While we have gained detailed insight into the molecules and neuronal networks responsible for the circadian organization of sleep and wakefulness, the molecular underpinnings of the homeostatic aspect of sleep regulation are still unknown and the focus of a considerable research effort. In the last 20 years, the development of techniques allowing the simultaneous measurement of hundreds to thousands of molecular targets (i.e. 'omics' approaches) has enabled the unbiased study of the molecular pathways regulated by and regulating sleep. In this chapter, we will review how the different omics approaches, including transcriptomics, epigenomics, proteomics, and metabolomics, have advanced sleep research. We present relevant data in the framework of the two-process model in which circadian and homeostatic processes interact to regulate sleep. The integration of the different omics levels, known as 'systems genetics', will eventually lead to a better understanding of how information flows from the genome, to molecules, to networks, and finally to sleep both in health and disease. PMID- 29796780 TI - Confirmatory factor analyses of the ORTO 15-, 11- and 9-item scales and recommendations for suggested cut-off scores. AB - AIMS: To explore the validity and recommend cut-off scores in an English-speaking sample for 9, 11, and 15-item versions of the ORTO measure for orthorexia, a proposed eating disorder characterised by a pathological obsession with consuming only 'healthy' foods. MATERIALS AND METHODS: The sample comprised of 585 participants (82.4% female) who completed an online questionnaire containing the ORTO-15, Eating Attitudes test, Obsessive Compulsive Inventory Revised. A series of Confirmatory Factor Analyses were conducted to test model fit. Binary logistic linear regression and receiver-operating-characteristics (ROC) analyses were used to obtain cut-offs. RESULTS AND CONCLUSION: Results showed that none of the three published versions (9, 11, and 15-item) of the ORTO produced an acceptable model. Subsequent exploratory and confirmatory factor analyses yielded a seven-item version of the ORTO (ORTO-7) with a strong and stable factor structure. Analysis of cut-offs revealed that a cut-off score of equal or greater than 19 on the ORTO 7 represents probable orthorexia. LEVEL OF EVIDENCE: Level V, descriptive study. PMID- 29796781 TI - Mitigating hypothetical bias in willingness to pay studies: post-estimation uncertainty and anchoring on irrelevant information. AB - One possible source of hypothetical bias in willingness to pay (WTP) estimates is response uncertainty, referring to subject's uncertainty about the value of the good under assessment. It has been argued that uncertainty can be measured using the post-valuation 'certainty question' that asks: 'How certain are you about your stated WTP?' and marks the degree of certainty on a quantitative or a qualitative scale. Research has shown that the self-reported certainty evaluations can help mitigate hypothetical bias and obtain increasingly accurate WTP estimates. These study reports present a simple test of reliability of post valuation certainty assessment and then looks at the empirical evidence for clues regarding the general usefulness of certainty adjustment in mitigating hypothetical bias in WTP studies. We find that the post-estimation uncertainty scores are malleable, i.e., significantly correlated with entirely irrelevant information. We conclude that more robust evidence could justify the routine inclusion of certainty evaluation in WTP studies although in the meantime the interpretation of certainty-adjusted WTP values should be approached cautiously. PMID- 29796783 TI - Correction to: Restricted working hours in Austrian residency programs : Survey results. AB - Correction to: Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1340 1 The original version of this article unfortunately contained a mistake. The presentation of the sentence "limiting on-duty working hours to 58h per week." was incorrect. The correct limitation of the on-duty working .... PMID- 29796782 TI - Competing Constructivisms: The Negotiation of PTSD and Related Stigma Among Post 9/11 Veterans in New York City. AB - Posttraumatic stress disorder (PTSD) stands as a form of psychopathology that straddles moral and psychiatric domains. Grounded in discrete instances of trauma, PTSD represents an etiological outlier in an era of increased attention to the genetics of mental illness and a prime location for social constructivist analyses of mental illness. This examination of PTSD narratives-as voiced in qualitative interviews and focus groups with 50 veterans of the recent Iraq and Afghanistan wars living in New York City-attends to the processes through which veterans conceive and navigate PTSD symptoms and diagnoses. In so doing we highlight the social constructivist positions undertaken by veterans themselves as they varyingly challenge and internalize symptomology in dialogue with psychiatric definitions and the stigma associated with PTSD. Findings demonstrate the rejection of classic psychopathological etiology-in brain disease, for example-by many veterans as well as the complex balancing of benefit and stigma that veterans undertake when making decisions about presenting to psychiatric clinicians. Drawing on veterans' accounts, we argue for greater cultural specificity in characterizing the diagnosis-seeking behavior of trauma survivors and a greater appreciation for the contradictions and compromise related to both acceptance and rejection of a mental health diagnosis. PMID- 29796784 TI - What is new in the 2017 ESC clinical practice guidelines : Management of acute myocardial infarction in patients presenting with ST-segment elevation. AB - Guidelines and recommendations are designed to guide physicians in making decisions in daily practice. Guidelines provide a condensed summary of all available evidence at the time of the writing process. Recommendations take into account the risk-benefit ratio of particular diagnostic or therapeutic means and the impact on outcome, but not monetary or political considerations. Guidelines are not substitutes but are complementary to textbooks and cover the European Society of Cardiology (ESC) core curriculum topics. The level of evidence and the strength of recommendations of particular treatment options were recently newly weighted and graded according to predefined scales. Guidelines endorsement and implementation strategies are based on abridged pocket guidelines versions, electronic version for digital applications, translations into the national languages or extracts with reference to main changes since the last version. The present article represents a condensed summary of new and practically relevant items contained in the 2017 European Society of Cardiology (ESC) guidelines for the management of acute myocardial infarction in patients with ST-segment elevation, with reference to key citations. PMID- 29796785 TI - Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study. AB - BACKGROUND: Leadless pacemaker systems are an important upcoming device in clinical rhythmology. Currently two different products are available with the Micra system (Medtronic) being the most used in the clinical setting to date. The possibility to perform magnetic resonance imaging (MRI) is an important feature of modern pacemaker devices. Even though the Micra system is suitable for MRI, little is yet known about its impact on artifacts within the images. OBJECTIVE: The aim of our ex vivo study was to perform cardiac MRI to quantify the artifacts and to evaluate if artifacts limit or inhibit the assessment of the surrounding myocardium. METHODS: After ex vivo implantation of the leadless pacemaker (LP) in a porcine model, hearts were filled with saline solution and fixed on wooden sticks on a plastic container. The model was examined at 1.5 T and at 3 T using conventional sequences and T2 mapping sequences. In addition, conventional X-rays and computed tomography (CT) scans were performed. RESULTS: Correct implantation of the LP could be performed in all hearts. In almost all MRI sequences the right ventricle and the septal region surrounding the (LP) were altered by an artifact and therefore would sustain limited assessment; however, the rest of the myocardium remained free of artifacts and evaluable for common radiologic diagnoses. A characteristic shamrock-shaped artifact was generated which appeared to be even more intense in magnitude and brightness when using 3 T compared to 1.5 T. CONCLUSION: The use of the Micra system in cardiac MRI appeared to be feasible. In our opinion, it will still be possible to make important clinical cardiac MRI diagnoses (the detection of major ischemic areas or inflammatory processes) in patients using the Micra system. We suggest the use of 1.5 T as the preferred method in clinical practice. PMID- 29796786 TI - Missed Opportunities for HIV Testing Among STD Clinic Patients. AB - Current HIV testing guidelines recommend that all adolescents and adults aged 13 64 be routinely screened for HIV in healthcare settings. Sexually transmitted disease (STD) clinic patients represent a population at increased risk for HIV, justifying more frequent risk assessment and testing. This analysis describes missed opportunities for HIV testing among a sample of STD clinic patients to identify areas where HIV testing services may be improved. Secondary analysis was conducted using data from Project AWARE, a randomized trial of 5012 adult patients from 9 STD clinics in the United States, enrolled April-December 2010. HIV testing history, healthcare service utilization, and behavioral risks were obtained through audio computer-assisted self-interview. Missed opportunities for HIV testing, defined as having a healthcare visit but no HIV test in the last 12 months, were characterized by location and frequency. Of 2315 (46.2%) participants not tested for HIV in the last 12 months, 1715 (74.1%) had a missed opportunity for HIV testing. These missed opportunities occurred in both traditional (54.9% at family doctor, 20.3% at other medical doctor visits) and non-traditional (28.5% at dental, 19.0% at eye doctor, 13.9% at correctional facility, and 13.3% at psychology visits) testing settings. Of 53 participants positive for HIV at baseline, 16 (30.2%) had a missed testing opportunity. Missed opportunities for HIV testing were common in this population of STD clinic patients. There is a need to increase routinized HIV screening and expand testing services to a broader range of healthcare settings. PMID- 29796787 TI - Isolation and characterization of human urine extracellular vesicles. AB - Extracellular vesicles (ECV) reflect physiological or pathological conditions, emerging as potential biomarkers for disease. They can be obtained from a variety of body fluids, particularly urine that is an ideal source because it can be obtained in great quantities, recurrently and with minimal intervention. However, the characterization of urine ECV is challenging because the preparation is usually contaminated with soluble proteins, such as uromodulin (UMOD) or Tamm Horsfall glycoprotein that forms large extracellular filaments co-sedimenting with ECV. We developed a method to obtain human urine ECV free of UMOD by the addition of ZnSO4 prior to vesicle isolation by differential centrifugation. Treatment with ZnSO4 did not affect the size and concentration of the vesicle preparation and preserved the storage of the samples at low temperatures. We did not observe a variation in the number of vesicles isolated during different times of the day or different days between different donors. The glycoprotein pattern of urine ECV was characterized by binding to concanavalin A (Con A) and mass spectroscopy. Several markers were found, including dipeptidyl peptidase IV (CD26), vacuolar protein sorting factor 4A (VPS4A) and dipeptidase 1 (DPEP1), and galectin 3 binding protein (G3-BP). The levels of VPS4A and DPEP1 were similar in ECV preparations obtained from several donors of both sexes. Con A binding pattern and monosaccharide composition were also comparable between subjects. In summary, our method for the isolation of highly pure ECV derived from human urine is likely to help in the use of these vesicles as potential biomarkers. PMID- 29796788 TI - Bio-production of Baccatin III, an Important Precursor of Paclitaxel by a Cost Effective Approach. AB - Natural production of anti-cancer drug taxol from Taxus has proved to be environmentally unsustainable and economically unfeasible. Currently, bioengineering the biosynthetic pathway of taxol is an attractive alternative production approach. 10-deacetylbaccatin III-10-O-acetyl transferase (DBAT) was previously characterized as an acyltransferase, using 10-deacetylbaccatin III (10 DAB) and acetyl CoA as natural substrates, to form baccatin III in the taxol biosynthesis. Here, we report that other than the natural acetyl CoA (Ac-CoA) substrate, DBAT can also utilize vinyl acetate (VA), which is commercially available at very low cost, acylate quickly and irreversibly, as acetyl donor in the acyl transfer reaction to produce baccatin III. Furthermore, mutants were prepared via a semi-rational design in this work. A double mutant, I43S/D390R was constructed to combine the positive effects of the different single mutations on catalytic activity, and its catalytic efficiency towards 10-DAB and VA was successfully improved by 3.30-fold, compared to that of wild-type DBAT, while 2.99-fold higher than the catalytic efficiency of WT DBAT towards 10-DAB and Ac CoA. These findings can provide a promising economically and environmentally friendly method for exploring novel acyl donors to engineer natural product pathways. PMID- 29796790 TI - Successful repair using thymus pedicle flap for tracheoesophageal fistula: a case report. AB - BACKGROUND: Treatment for tracheoesophageal fistula (TEF), a life-threatening complication after esophagectomy, is challenging. CASE PRESENTATION: A 75-year old man with thoracic esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the post-mediastinal root after neoadjuvant chemotherapy. Owing to postoperative anastomotic leakage, an abscess formed at the anastomotic region. Sustained inflammation from the abscess caused refractory TEF between the esophagogastric anastomotic site and membrane of the trachea, and several conservative therapies for TEF failed. Hence, the patient underwent surgery including division of the fistula, direct suturing of the leakage sites, and reinforcement with the flap of the thymus pedicle. As a result, the abscess and TEF disappeared after surgery and the patient was immediately administered an oral diet and discharged home 103 days after initial surgery. CONCLUSIONS: Although pedicle flaps for the reinforcement of TEF are usually obtained from muscle or pericardium, these flaps need enough lengths to overcome moving distance. We are the first in the existing literature to have successfully treated TEF with surgical repair using a thymus flap located close to TEF. The thymus pedicle might be another candidate for the reinforcement flap in TEF. PMID- 29796789 TI - Multiple frequency saturation pulses reduce CEST acquisition time for quantifying conformational exchange in biomolecules. AB - Exchange between conformational states is required for biomolecular catalysis, allostery, and folding. A variety of NMR experiments have been developed to quantify motional regimes ranging from nanoseconds to seconds. In this work, we describe an approach to speed up the acquisition of chemical exchange saturation transfer (CEST) experiments that are commonly used to probe millisecond to second conformational exchange in proteins and nucleic acids. The standard approach is to obtain CEST datasets through the acquisition of a series of 2D correlation spectra where each experiment utilizes a single saturation frequency to 1H, 15N or 13C. These pseudo 3D datasets are time consuming to collect and are further lengthened by reduced signal to noise stemming from the long saturation pulse. In this article, we show how usage of a multiple frequency saturation pulse (i.e., MF-CEST) changes the nature of data collection from series to parallel, and thus decreases the total acquisition time by an integer factor corresponding to the number of frequencies in the pulse. We demonstrate the applicability of MF-CEST on a Src homology 2 (SH2) domain from phospholipase Cgamma and the secondary active transport protein EmrE as model systems by collecting 13C methyl and 15N backbone datasets. MF-CEST can also be extended to additional sites within proteins and nucleic acids. The only notable drawback of MF-CEST as applied to backbone 15N experiments occurs when a large chemical shift difference between the major and minor populations is present (typically greater than ~ 8 ppm). In these cases, ambiguity may arise between the chemical shift of the minor population and the multiple frequency saturation pulse. Nevertheless, this drawback does not occur for methyl group MF-CEST experiments or in cases where somewhat smaller chemical shift differences occur are present. PMID- 29796792 TI - Livestock and livelihoods of smallholder cattle-owning households in Cambodia: the contribution of on-farm and off-farm activities to income and food security. AB - The majority of smallholder farming households in Cambodia are rurally based and rely on agriculture to support their livelihoods. However, in recent years, growth in the agriculture sector has stagnated with farmers facing several challenges including declining prices for traditional crops and irregular rainfall patterns. This has led to a need for farmers to diversify income sources with livestock promoted as a more viable livelihood activity, particularly the raising of cattle and poultry. However, uncertain profitability of livestock activities is a common perception by smallholders, especially where animals have not been traditionally viewed as a primary income source. To address this, information is required which compares the income and expenses associated with livestock raising to other on-farm activities and off-farm sources. This study reports on a survey of livelihood survey of 17 male and 21 female representatives of 20 households owning cattle in Cambodia, comparing the associated income and expenses of the various livelihood activities in the 12-month period from January to December 2016. Combined total household income from both on-farm and off-farm sources ranged from USD875 to 17730 with an average of USD6779, representing 51% and 49% from on-farm and off-farm activities, respectively. Cattle raising was the most common source of on-farm income (85%), contributing USD1064 and representing 22% of total household income. General household expenses, such as food and transportation (including expenses associated with off-farm employment), represented the majority of total household expenses (79%). Gross profit calculations indicated higher values for pig raising (USD1841.79), cattle (USD950.80) and non-rice crops (USD884) whilst the highest gross margin value was recorded for cattle (89.33%) followed by vegetables (85.27%) and non-rice crops (83.08%). Whilst wet season and dry season rice returned a negative gross profit value of USD197.27 and USD90.60 on average per household, respectively, both were ranked as most important for household consumption, followed by poultry, providing the main source of energy (rice) and protein (chicken meat) and sustaining household food requirements. The study concludes that although smallholder cattle-owning households in Cambodia undertake a diverse range of on farm activities, as cattle raising provides a superior income source due to higher returns and lower variable costs, it could be promoted as a preferred livelihood activity by agencies conducting rural extension activities. Although consideration of available labour and monetary funds to invest in cattle raising is required, it was observed that income from off-farm sources may prove beneficial in providing the additional monetary funds to support cattle-raising activities and assist in providing generally poor smallholder households with enhanced economic resilience. PMID- 29796791 TI - Effect of feeding slowly fermentable grains on productive variables and amelioration of heat stress in lactating dairy cows in a sub-tropical summer. AB - Feeding low-fiber and high-energy diets to dairy cows is one approach to ameliorate heat stress (HS) by reducing heat increment (HI) during digestion. However, rapidly and slowly fermentable cereal grains differ in their HI. The aim of this experiment was to quantify if feeding slowly fermentable grains ameliorated the physiological responses to HS and improved milk production (MP) in dairy cows. Holstein-Friesian lactating dairy cows were housed in shaded pens and were fed either a total mixed ration (TMR) plus wheat (TMRW), a TMR plus wheat treated with 2% of a commercial starch-binding agent (TMRB), or a TMR plus corn (TMRC) (n = 8 cows per diet) during summer in Queensland, Australia. Respiration rate (RR) and panting score (PS) were measured four times a day; rumen temperature (RuT) was recorded every 20 min, and rectal temperature (RT) and milk samples were obtained every 4 days. Cows fed slowly fermentable grains had higher milk production (MP) than cows fed TMRW, and cows fed TMRC had lower RT than those fed TMRW and TMRB (P < 0.001). Rumen temperature was positively correlated with temperature-humidity index and negatively correlated with MP (P < 0.05). In summary, feeding TMRC ameliorated HS as indicated by lower RT and improved MP in dairy cows. Milk production was improved with starch-binding agents; however, this was not associated with efficient thermoregulatory responses. Furthermore, determination of RuT enabled the prediction of changes in physiological variables and productive responses due to HS in lactating dairy cows. PMID- 29796793 TI - Editorial: Special Issue on Immunohistochemical Biomarkers in Endocrine Pathology. PMID- 29796794 TI - European Society of Paediatric Radiology Abdominal Imaging Task Force recommendations in paediatric uroradiology, part X: how to perform paediatric gastrointestinal ultrasonography, use gadolinium as a contrast agent in children, follow up paediatric testicular microlithiasis, and an update on paediatric contrast-enhanced ultrasound. AB - At the European Society of Paediatric Radiology (ESPR) annual meeting 2017 in Davos, Switzerland, the ESPR Abdominal (gastrointestinal and genitourinary) Imaging Task Force set out to complete the suggestions for paediatric abdominal imaging and its procedural recommendations. Some final topics were addressed including how to perform paediatric gastrointestinal ultrasonography. Based on the recent approval of ultrasound (US) contrast agents for paediatric use, important aspects of paediatric contrast-enhanced US were revisited. Additionally, the recent developments concerning the use and possible brain deposition of gadolinium as a magnetic resonance imaging contrast agent were presented. The recommendations for paediatric use were reissued after considering all available evidence. Recent insights on the incidence of neoplastic lesions in children with testicular microlithiasis were discussed and led to a slightly altered recommendation. PMID- 29796795 TI - Shaken baby syndrome is real. PMID- 29796796 TI - Correction to: Carotid artery intima-media thickness measurement in children with normal and increased body mass index: a comparison of three techniques. AB - The original version of this article contained a mistake in Fig. 1: The old version was used during figure processing instead of the replacement. The correct figure is shown below. The original article has been corrected. PMID- 29796798 TI - Goliath as an acromegalic giant by Giovanni Lanfranco (1582-1647). PMID- 29796799 TI - Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto's thyroiditis. AB - PURPOSE: Interleukin-37 (IL-37), member of the IL-1 family, is a natural suppressor of immune and inflammatory responses. Increased serum IL-37 levels were observed in several autoimmune diseases, including Graves' disease. To our knowledge, no data on Hashimoto's thyroiditis (HT) are available in the literature. METHODS: Aim of our study was to measure serum IL-37 levels and evaluate their relationship, if any, with oxidative stress markers in HT patients. We enrolled 45 euthyroid HT patients (5 M e 40 F, median age 40 years) and 50 age- and sex-matched healthy controls. None was under L-thyroxine therapy. Serum IL-37 levels were measured by ELISA. Specific serum tests, such as derived reactive oxygen metabolites (d-ROMs), and biological anti-oxidant potential (BAP) test were performed in all subjects to investigate the changes in oxidative balance, and advanced glycation end products (AGEs) were determined as a specific marker of oxidative stress. RESULTS: IL-37 levels were significantly higher in HT than in controls (median 475 vs. 268 pg/ml, P = 0.018). In the same patients, serum oxidants (d-ROMs) were increased and anti-oxidants (BAP) decreased compared with controls (P = 0.011 and < 0.0001, respectively), clearly indicating an enhanced oxidative stress. In addition, AGEs levels were higher in HT patients than in controls (210 vs. 140 AU/g prot, P < 0.0001) and directly correlated with IL-37 levels (P = 0.048). At multivariate analysis, the main independent predictors that influenced IL-37 levels were both anti-thyroid antibodies (P = 0.026) and AGEs levels (P = 0.001). CONCLUSIONS: IL-37 is up-regulated in HT and may exert a protective role by counteracting oxidative stress and inflammation. PMID- 29796800 TI - Correction to Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo. AB - The author name M. V. Edeeva should read M. V. Edeleva. PMID- 29796801 TI - KrioBlast(r) as a New Technology of Hyper-fast Cryopreservation of Cells and Tissues. Part II. 2. Kinetic Vitrification of Human Pluripotent Stem Cells and Spermatozoa [corrected]. AB - Pilot experiments on kinetic vitrification of human pluripotent stem cells and spermatozoa using a KrioBlastTM-2 without penetrating cryoprotectants have shown high survival of cells (75-85% in both cases). PMID- 29796802 TI - Real-Time Recording of Platelet Adhesion to Fibrinogen-Coated Surface under Flow Conditions. AB - We present a testing system allowing real-time recording of the kinetics of platelet adhesion to fibrinogen-coated surface under flow conditions. The system consists of an optical flow chamber, semiconductor laser, two photodetectors, analog-to-digital converter, computer, and peristaltic pump. Platelet adhesion to fibrinogen-coated surface is recorded with two photodetectors and analyzed by the intensity of total internal reflection and scattered laser radiation at the boundary of the blood sample and fibrinogen-coated optical surface. Kinetics of platelet adhesion was studied as a function of shear rate and platelet concentration. The specificity of platelet adhesion with proteins on the surface of the flow chamber was verified by blocking IIb/IIIa glycoprotein complex on platelets with Fab2 fragments of monoclonal antibodies. PMID- 29796797 TI - Consensus statement on abusive head trauma in infants and young children. AB - Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. A multidisciplinary team bases this diagnosis on history, physical examination, imaging and laboratory findings. Because the etiology of the injury is multifactorial (shaking, shaking and impact, impact, etc.) the current best and inclusive term is AHT. There is no controversy concerning the medical validity of the existence of AHT, with multiple components including subdural hematoma, intracranial and spinal changes, complex retinal hemorrhages, and rib and other fractures that are inconsistent with the provided mechanism of trauma. The workup must exclude medical diseases that can mimic AHT. However, the courtroom has become a forum for speculative theories that cannot be reconciled with generally accepted medical literature. There is no reliable medical evidence that the following processes are causative in the constellation of injuries of AHT: cerebral sinovenous thrombosis, hypoxic-ischemic injury, lumbar puncture or dysphagic choking/vomiting. There is no substantiation, at a time remote from birth, that an asymptomatic birth-related subdural hemorrhage can result in rebleeding and sudden collapse. Further, a diagnosis of AHT is a medical conclusion, not a legal determination of the intent of the perpetrator or a diagnosis of murder. We hope that this consensus document reduces confusion by recommending to judges and jurors the tools necessary to distinguish genuine evidence-based opinions of the relevant medical community from legal arguments or etiological speculations that are unwarranted by the clinical findings, medical evidence and evidence-based literature. PMID- 29796803 TI - Effect of Intramuscular Administration of Mesenchymal Stem Cells and Erythropoietin on Angiogenesis in Critical Limb Ischemia. AB - We studied the effect of intramuscular injections of bone marrow mesenchymal stromal cells on microcirculation parameters in an ischemic limb of Wistar rats. It was shown that transplantation of mesenchymal stem cells with or without erythropoietin stimulates angiogenesis in the ischemic zone. An essential role in angiogenesis stimulation is played by cytokines and growth factors. PMID- 29796804 TI - Endothelial Cells Modulate Differentiation Potential and Mobility of Mesenchymal Stromal Cells. AB - We studied the effect of endothelial cells on in vitro migration and differentiation potential of multipotent mesenchymal stromal cells. Down regulation of stemness genes OCT4, SOX2, and chondrogenic differentiation regulator SOX9 gene and upregulation of osteogenesis master-gene RUNX2 in mesenchymal stromal cells were observed in the presence of intact and TNFalpha activated endothelial cells, which indicated an increase in commitment of mesenchymal stromal cells.The medium conditioned by endothelial cells stimulated migration activity of mesenchymal stromal cells; migration rate increased significantly in conditioned medium from activated cells in comparison with medium from non-activated cells. It was concluded that the interaction with endothelial cells modulated functional activity of mesenchymal stromal cells; moreover, activated endothelial cells produced more pronounced effects on differentiation potential and migration activity of mesenchymal stromal cells both in direct contact and through paracrine regulation. PMID- 29796805 TI - Peculiarities of Molecular Mechanisms Involved in Modification of the Structural and Molecular Organization of the Cell Genome. AB - Within the framework of the previously proposed model of structural organization of DNA that supplements the Watson-Crick model and is based on a mathematical regulation - Fibonacci sequence, we suppose the existence of nucleotides without nitrogenous base and acting as linkers connecting DNA subunits. PMID- 29796806 TI - Isolation of Rat Olfactory Ensheathing Cells and Their Use in the Therapy of Posttraumatic Cysts of the Spinal Cord. AB - We evaluated the efficacy of rat olfactory ensheathing cells in the therapy of experimental cysts of the spinal cord. Improvement of the motor function of the hind limbs after transplantation of the olfactory ensheathing cells into the posttraumatic spinal cord cysts rats was found. We also determined the required number of cells for transplantation and demonstrated a neuroprotective effect of this dosage. For further clinical studies, autologous tissue-specific cell preparation of olfactory ensheathing cells has to be created. Cell therapy in combination surgical and pharmacological treatment will substantially improve the quality of life of patients with posttraumatic spinal cord cysts. PMID- 29796807 TI - Composition of the Stabilizer and Conditions of Lyophilization for Preserving Infectious Activity of Influenza Virus. AB - For stabilization of vaccine preparations, they are lyophilized. The composition of the protective medium is an important parameter affecting the quality of the vaccine after drying. In view of the risk of spreading prion diseases, the use of media containing animal proteins is not recommended. In this study, protective media containing no animal proteins and lyophilization regimen were determined. The optimum lyophilization regimen consisted of three stages: freezing at -70 degrees C, main stage at -35 degrees C, and drying at 24 degrees C. Protective medium containing 4% trehalose or protective medium with 10% sucrose and 5% soy peptone ensured highest stability of the lyophilized vaccine preparation in temperature range of 4-24 degrees C. This can help to overcome possible break in the cold chain, which is important during transporting or storage of vaccine preparations. PMID- 29796808 TI - Cell Death and Development of Fibrotic Alterations in Lung Granuloma of BALB/c Mice during Chronic BCG-Induced Granulomatosis. AB - Light microscopy, immunohistochemistry, and morphometric examinations established that cell death in lung granulomas of BCG-infected mice resulted mainly from activation of receptor-mediated apoptosis, which did not prevent the persistence of the causative agent in macrophages of the granulomas and promoted the formation of pronounced fibrosis in granulomas and pulmonary interstitium. PMID- 29796809 TI - Matrix Metalloproteinases and Their Tissue Inhibitors in Blood Serum of Patients with Endometrial Cancer: Clinical and Morphological Correlations. AB - In patients with endometrial cancer (N=94), endometrial polyps (N=28), endometrial hyperplasia (N=25), and healthy women (N=77), the serum contents of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA. Both carcinoma and benign neoplasms were accompanied by significant elevation of MMP-7 and TIMP 2 in blood serum. The greatest elevation (in comparison with the control) was observed for MMP-7, although serum concentration of this marker was practically identical in patients with carcinoma and benign tumors. In contrast, the levels of MMP-2 and TIMP-1 were lower in cancer patients in comparison with the control; in these patients, the levels of MMP-9 and TIMP-1 were also lower than the corresponding levels in patients with polyps and endometrial hyperplasia. There were no significant correlations between the levels of examined markers with tumor metastasizing, its histological structure, and differentiation degree of endometrial cancer. No differences were observed between examined serological markers in patients with polyps and endometrial hyperplasia of various severities. The examined MMPs and TIMPs cannot be advanced as potential diagnostic markers of endometrial cancer, but they can be used to monitor and prognosticate the disease and to assess effectiveness of the targeted therapy. PMID- 29796810 TI - Heart Rhythm Disturbances Caused by Injection of Cholinesterase Inhibitor Physostigmine to Rats during the Early Ontogeny. AB - Parameters of cardiac activity after administration of the cholinesterase inhibitor physostigmine were analyzed in newborn rats and on day 16 of postnatal development. The type of cardiovascular response to acetylcholine excess in newborns and 16-day-old rats were similar, but they significantly differed by the magnitude, which suggests that that maturation of cholinergic structures involved in the regulation of cardiac activity is completed during the early postnatal ontogeny. PMID- 29796811 TI - Preventive Effects of Oxidized Dextran on Functional Activity of Pulmonary Macrophages in Mice Infected with Influenza A Virus. AB - We analyzed cytokine profile of pulmonary macrophages in mice infected with highly pathogenic influenza A/H5N1 virus after preventive injections of oxidized dextran. Light microscopy, immunohistochemistry, and morphometric examinations showed that preventive injections of oxidized dextran led to more effective virus elimination, modulation of the proinflammatory cytokine response, and host antiviral response and reduce animal mortality. Our findings allow recommending oxidized dextran for further studies in order to create a vaccine with antiviral and adjuvant potencies. PMID- 29796812 TI - In Vitro Effects of Sodium Nitroprusside and L-Nomega-Nitroarginine Methyl Ester (L-NAME) on Activity of Lysosomal Cysteine Proteinases and Lysosomal Membrane Permeability. AB - The direct effect of 5 mM L-NAME and 0.1 mM sodium nitroprusside on activity of lysosomal cysteine proteinases and permeability of lysosomal membrane was studied in vitro after 1, 2, and 4 h of incubation. Isolated from the liver of intact female rats lysosome suspensions were used. Both substances reduced total activity of cathepsin H and did not affect cathepsin B at all time intervals. L NAME increased cathepsin L activity at all incubation times, while sodium nitroprusside increased activity of this enzyme after 2-h incubation and reduced it incubation after 4-h incubation. L-NAME demonstrated a membrane-destabilizing effect in in vitro experiments, while sodium nitroprusside on the contrary stabilized lysosomal membranes. PMID- 29796813 TI - Protective Role of Nitrate/Nitrite Reductase System during Transient Global Cerebral Ischemia. AB - The effects of a non-selective blocker of NO synthases LNNA in a dose of 25 mg/kg and nitrates KNO3, NaNO3, Mg(NO3)2, and Ca(NO3)2 in doses of 5 and 50 mg/kg were studied on the model of experimental ischemic stroke induced by bilateral occlusion of the common carotid arteries. Wistar rats were randomized into 40 treatment (n=960) and 8 control (n=192) groups. Treatment group rats received injection of either nitrate, or LNNA, or a combination LNNA+nitrate. All substances were administered intraperitoneally 1 h prior to brain ischemia or 5 sec after occlusion of the common carotid arteries. Control rats received the same volume of 0.9% NaCl at the same terms. The non-selective inhibitor of NO synthases LNNA administered against the background of brain ischemia increased neurological deficit and animal mortality. Nitrate/nitrite reductase system had protective properties depending on the cation of nitrate and concentration of a nitrate during inhibition of NO synthase system under conditions of brain ischemia and hypoxia. PMID- 29796814 TI - Radioprotective Properties of Neomitilan in Experimental Radiation Pneumonia. AB - The efficiency of neomitilan, a polysaccharide isolated from Crenomytilus grayanus mussels, was studied in experimental model of radiation pneumonia (irradiation of the animal lungs with a total dose of 14 and 28 Gy). Histological study showed that an increase in the number of nucleated components in the lungs of animals subjected to neomitilan inhalation prior to irradiation. Proliferation of bronchial epitheliocytes and the formation of additional lymphoid structures were also revealed in these animals. The absence of a tendency to lung tissue recovery in animals irradiated with 28 Gy is due to extreme radiation toxicity. PMID- 29796815 TI - Retinoblastoma Cell Culturing and Evaluation of Their Drug Resistance. AB - We obtained primary culture of retinoblastoma cells and evaluated the resistance of cultured ells to chemotherapy. The study included 19 patients aged 6-64 months (mean 27.9+/-17.4 months); of these, 6 (31.6%) patients with bilateral retinoblastoma and 13 (68.4%) patients with unilateral form. In 18 (94.7%) patients, group E retinoblastoma was diagnosed. Enucleation was performed in all patients; in 94.7% cases, low-differentiated retinoblastoma was identified. Samples of the tumor tissue were taken to derive a cell culture and to study drug resistance and metabolic activity of cells (MTT test). In 4 cases, adhesion primary cultures of retinoblastoma were derived. Cytological verification of the obtained cultures was performed. The primary cultures were derived from 4 of 6 bilateral tumors and from none of 13 unilateral tumors (p=0.003). There were no statistically significant correlations with patient age (p=0.33) and the presence of calcifications in the tumor (p=0.26). MTT test revealed no differences in the sensitivity of cell cultures to irinotecan and ifosfamide. Pronounced differences in the resistance of cell cultures were observed for oxaliplatin and ascorbic acid. MTT test with evaluation of drug resistance can be used both in clinical practice for adjusting chemotherapy regimen and in development of new approaches to the treatment of retinoblastoma with assessment of in vivo tumor cell resistance in animal models. PMID- 29796817 TI - Dynamics of Expression of Cytokine Genes and Macrophage Content in the Lungs and Kidneys after Subtotal Hepatectomy in Rats. AB - The role of the lungs and kidneys in liver regeneration after subtotal hepatectomy was studied on a rat model. It was found that production of hepatocyte growth factor (HGF) in the lungs and kidneys and expression of cytokine genes Il1b, Il6, Il10, and tnfa significantly increased. Analysis of the dynamics of lung macrophage population showed that accumulation of HGF and the increase in the expression of cytokine genes in the lungs were accompanied by simultaneous increase in the number of CD68+ cells, which attested to the leading role of macrophages in activation of HGF synthesis in the lungs. Macrophage content in the kidneys after subtotal hepatectomy did not increase. PMID- 29796816 TI - Reinforced Hybrid Collagen Sponges for Tissue Engineering. AB - We created an anisotropic material based on collagen sponge and reactive polylactide structured by laser photopolymerization. The combination of collagen with reactive polylactide improves the resistance of the formed matrices to biodegradation in comparison with collagen sponge, while the existence of sites with different mechanical characteristics and cell affinity on the matrix provides directed cell growth during their culturing. It was shown that reinforcement of the collagen sponges 7-fold increased the mean Young's modulus for the hybrid matrix without affecting its cytotoxicity. The developed matrix provides cell adhesion and proliferation along reinforcement lines and can be used for fabrication of tissue engineering constructs. PMID- 29796818 TI - Differences in the Expression of TLR-2, NOD2, and NF-kappaB in Placenta Between Twins. AB - Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-kappaB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-kappaB, NOD2 and TLR-2 between twins. In case of twin-to twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment. PMID- 29796819 TI - Endoscopic transperineal pudendal nerve decompression: operative pudendoscopy. AB - BACKGROUND: Pudendal nerve entrapment can produce a pudendal syndrome comprising perineodynia together with urinary, sexual, and anorectal symptoms. This syndrome can be treated surgically by the transperineal approach. By using an endoscope during the procedure ("operative pudendoscopy"), the surgeon has close-up visual control of each decompression steps, demonstrates the different levels of entrapment, and cuts the sacrospinous ligament under visual control. The aim of this study was to describe the technical details of this new technique and its outcome in the treatment of the pudendal syndrome. METHODS: A series of 113 patients with severe pudendal syndrome underwent operative pudendoscopy. A complete history, pain visual analog scale (VAS) for perineodynia, and four scores evaluating the main symptoms (ICIQ-SF, NHI-CPSI, St Mark's, and Wexner) were obtained before and at least 24 months after surgery. The three clinical signs of pudendal syndrome (abnormal pinprick sensitivity, painful skin rolling test, and painful pudendal nerve) and perineal descent were analyzed before and after surgery in 91 patients. RESULTS: The mean operating time per side was 50.3 +/- 15.2 min and the average hospital stay was 2.1 +/- 0.4 days. Perineodynia VAS dropped from 7.2 +/- 1.4 to 4.5 +/- 2.9 after surgery (p < 0.0001) and the symptoms scores significantly improved. Frequency of sexual arousal syndrome, dyspareunia, and cystalgia was also significantly reduced. Pathological perineal descent (>= 1.5 cm measured with a Perineocaliper(r)) observed in 13 patients was reduced from 1.81 to 0.77 cm after surgery (p < 0.0001). The only significant complication was severe hemorrhage in one patient induced by an inferior gluteal vessel laceration and successfully treated by arterial embolization. CONCLUSIONS: A complete pudendal nerve decompression, from the distal branches to the sacral foramina, safely performed under visual control by using operative pudendoscopy markedly improves clinical signs and symptoms of the pudendal syndrome. PMID- 29796820 TI - Head salvage of an infected neck of femur fracture in an adult: a case report. AB - Head preservation of an infected neck of femur fracture appears to be extremely rare with no described cases in literature till date. We present the outcome of head salvage in a young adult with an infected neck of femur nonunion who in addition had chronic osteomyelitic sequelae of his entire femur with reactivation of latent infection in the distal femoral diaphysis. Osteosynthesis was performed by means of cancellous screw fixation augmented with bone substitute following a failed attempt at salvage with a valgus intertrochanteric osteotomy. The patient had an excellent functional outcome with near normal hip range of movements at a follow-up of 5 years after union. PMID- 29796821 TI - An anatomical study on the effectiveness of Arthrex Mini TightRope(r) ligament reconstruction in an unstable trapeziometacarpal joint. AB - INTRODUCTION: Laxity in the trapeziometacarpal (TMC) joint is a debilitating condition usually affecting a young population. It can be treated operatively with ligament reconstruction. The purpose of this study was to determine the effectiveness of the Arthrex Mini TightRope(r) in reinforcing the stabilizing ligaments in an unstable TMC joint without decreasing the range of motion of the thumb. This method was compared with the "gold standard" published by Eaton and Littler in 1973. MATERIALS AND METHODS: Six fresh frozen arms from five cadavers were included. TMC joint laxity was measured on stress view radiographs as the ratio of the radial subluxation (RS) of the first metacarpal in relation to the trapezium, by the first metacarpal articular width (AW) (as described by Wolf in 2009). Measurements of the pre- and post-operative range of motion (ROM) were performed and compared. RESULTS: Both the Arthrex Mini TightRope(r) and the Eaton Littler stabilization improved the stability of the TMC joint. The pre-operative laxity value (ratio RS/AW) of 0.27 was significantly (P = 0.02) improved by each of the surgical interventions (Eaton-Littler RS/AW = 0.05 and Tightrope RS/AW = 0.09). The pre- and post-operative range of motion was not significantly different by each of the surgical interventions. There were no significant differences between the two stabilizing methods regarding laxity or range of motion. CONCLUSION: The Arthrex Mini TightRope(r) provided a good stabilization method for the TMC joint in this anatomical model without compromising the range of motion. PMID- 29796822 TI - Prevalence and anatomy of anomalous left vertebral artery originated from aorta evaluated by computed tomographic angiography. AB - PURPOSE: We evaluated anatomical characteristics and clinical significance of left vertebral artery (VA) originating from aortic arch (AA) by computed tomography (CT) angiography. METHODS: CT angiography was performed in 3460 patients between March 01, 2014 and November 30, 2015. We examined course of prevertebral VA (PVVA) segment and level of entry into the cervical vertebra transverse foramen (CVTF) of left VA originated from AA. RESULTS: One hundred fifty-three of 3460 patients had left VA originated from AA. Six of 153 patients had dual origin of VA. Entry level to CVTF of 156 left VAs in 153 cases ranged from C3 to C6. Entry level to CVTF of 156 right VAs in 153 cases ranged from C3 to C7. One hundred fifty-six right PVVA segments positioned in longus colli muscle lateral side in 112 VAs, longus colli muscle anterior surface near longus colli muscle lateral margin in 41 VAs, and unknown location in three VAs. One hundred fifty-six left PVVA segments positioned in anterior surface of longus colli muscle midline in 5 cases, anterior surface of longus colli muscle near longus colli lateral margin in 138 cases, longus colli muscle lateral side in 12 cases, and anterior surface of anterior scalene muscle midline in one case. CONCLUSIONS: Left VA may arise from the AA. If a long PVVA segment entering higher CVTF is present, operator can perform anterior cervical surgery via contralateral approach for avoidance of VA injury. PMID- 29796823 TI - Investigation on the benefits of mycophenolate mofetil and therapeutic drug monitoring in the treatment of Japanese patients with lupus nephritis. AB - BACKGROUND: Mycophenolate mofetil (MMF) is recommended as a first-line immunosuppressant to treat lupus nephritis (LN). Prognosis and therapeutic response in LN are known to vary depending on race. We investigated the benefits of MMF and therapeutic drug monitoring (TDM) in the treatment of Japanese LN patients. METHODS: In this retrospective cohort study, a total of 20 patients with LN who started MMF treatment were included. Clinical data were collected regularly after MMF administration. We evaluated complete remission (CR) rate as the primary outcome. Predictors of CR were identified using univariate and multivariate analyses. In the research of TDM, the correlation with the area under the curve (AUC) was analyzed at MMF dose, single-point value, treatment response, and adverse events. RESULTS: Overall, 70% of cases showed CR; both flare-ups and refractory cases had favorable results. Cases of LN with nephrotic syndrome (NS) or class III/IV + V showed a significantly lower CR rate (p < 0.005). The ratio of maintaining CR after MMF therapy was as high as 85.7%. In multivariate analysis, NS was an independent negative predictor of CR (HR 0.09, 95% confidence interval 0.01-0.81; p = 0.03). The relationship between AUC and MMF dose was low, and AUC correlated with trough level (r = 0.73). AUC tended to be high in the treatment responder (p = 0.09), but did not correlate with adverse events of infection (p = 0.92). CONCLUSION: MMF is a beneficial treatment option for Japanese LN patients, and further investigation on TDM-based therapy is needed. PMID- 29796824 TI - Follicular Lymphoma: Past, Present, and Future. AB - OPINION STATEMENT: Even in the modern era, follicular lymphoma (FL) remains largely an incurable but treatable disease with both standard and novel treatment modalities. Despite the abundance of efficacious treatment modalities currently available, there is no universally agreed upon standard approach to treatment for patients with FL, particularly in the relapsed/refractory (R/R) setting. There is an increasing need for better tools to risk-stratify patients and to identify those likely to experience relapse early. Additionally, the use of gene expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis; however, much of this knowledge is not currently applicable on a day to day basis in the clinic setting. Further studies are needed to determine a validated, clinically relevant predictive model that incorporates patient factors and molecular factors that will guide clinicians on the most effective treatment strategy. With many questions left unanswered, it is our opinion that the treatment of FL and sequencing of therapy in the R/R setting should be a personalized approach that balances patient-specific factors such as preferences and comorbidities with treatment-related factors such as known response rates and toxicity profiles. PMID- 29796825 TI - C-arm fluoroscopy in orthopaedic surgical practice. AB - The use of C-arm fluoroscopy in intraoperative orthopaedic procedures has become an important tool in modern orthopaedic surgical practice. It enhances the technical proficiency of the surgeon in addition to reducing the morbidity and length of hospital stay of the patient. Despite the documented benefits of this device, there has been a growing concern about the increased radiation exposure to the surgical team. We therefore present the review of the literature on the usefulness of C-arm fluoroscopy, pitfalls in application of the machine as well as the harmful radiation effects and precautionary measures that need to be observed when using the C-arm fluoroscopy in orthopaedic surgical procedures. PMID- 29796826 TI - Wrist hemiarthroplasty for irreparable DRF in the elderly. AB - INTRODUCTION: The authors update their results of wrist hemiarthroplasty for irreparable distal radius fracture in the elderly, at a minimum of 2-year follow up. MATERIALS AND METHODS: Between 2011 and 2018, 25 consecutive independent elderly patients (24 female, 27 wrists) were treated with wrist hemiarthroplasty for distal radius fracture at a single institution. The average age was 77 years (range 65-88). They all were independent at home. A total of 19 wrists were treated at the acute stage, and 8 secondary procedures. The average follow-up was 32 months (range 24-44). RESULTS: There was no dislocation, loosening, infection nor removal of the implants. We observed 3 CRPS. At final follow-up, the average VAS pain was 1/10, mean forearm pronation/supination arc was 150 degrees , and mean active flexion-extension arc was 60 degrees . Average wrist extension was 36 degrees . Mean grip strength was 68% of contralateral side. Mean Lyon wrist score was 74%. Mean Quick DASH score was 26%, and mean PRWE score was 25%. DISCUSSION: Our data suggest that treatment of acute irreparable distal radius fracture in the independent elderly patient with a bone-preserving primary wrist hemiarthroplasty may be a viable option. Longer-term follow-up are needed to confirm these preliminary data. PMID- 29796827 TI - In vitro cell response on CP-Ti surfaces functionalized with TGF-beta1 inhibitory peptides. AB - Osseointegration of implants is conversely related to the generation of a fibrous tissue capsule around the implant by the host environment. Although TGF-beta1 plays many roles in regeneration processes, it is the cytokine to be mostly associated to the production of fibrotic tissue and thus, its inhibition has demonstrated to be beneficial to prevent several fibrotic reactions. Surface biofunctionalization enables the immobilization of biologically active molecules on an implant surface to tailor the biological response of the host. Here, we studied in vitro biological effects of biofunctionalized CP-Ti surfaces with a TGF-beta1 inhibitor peptide, P144. A reliable biofunctionalization process that tethers P144 peptides to commercially pure titanium was developed. Differentiation of human mesenchymal stem cells, osteoblasts and fibroblasts on P144-functionalized and control surfaces was assessed at the gene expression and protein production levels. Results showed that P144-functionalized surfaces reduced expression and production of fibrotic differentiation markers and increased osteoblastic differentiation markers. Therefore, biofunctionalization of surfaces with TGF-beta1 inhibitor peptides are an alternative promising strategy for inducing osseointegration around medical devices and implants. PMID- 29796828 TI - A Multi-Responsive Naphthalimide-Based "Turn-on" Fluorescent Chemosensor for Sensitive Detection of Trivalent Cations Ga3+, Al3+ and Cr3. AB - A new multifunctional chemosensor 1, (E)-2-(((2-hydroxynaphthalen-1 yl)methylene)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, based on naphtalimide and naphthaldehyde was developed, which showed the fluorescence responses to trivalent metal ions (Ga3+, Al3+ and Cr3+). Sensor 1 detected and differentiated selectively trivalent metal ions Ga3+, Al3+ and Cr3+ by fluorescence enhancement at different emissions. The association constant of Ga3+-2?1 complex is the highest one among those of the organic chemosensors reported, to date. The sensing mechanisms for Ga3+, Al3+ and Cr3+ were explained by UV-vis titrations, Job plots, ESI-mass analyses and theoretical calculations. PMID- 29796829 TI - The hindbrain is a site of energy balance action for prolactin-releasing peptide: feeding and thermic effects from GPR10 stimulation of the nucleus tractus solitarius/area postrema. AB - PURPOSE: Prolactin-releasing peptide (PrRP) is a neuropeptide that suppresses food intake and increases body temperature when delivered to the forebrain ventricularly or parenchymally. However, PrRP's receptor GPR10 is widely distributed throughout the brain with particularly high levels found in the dorsomedial hindbrain. Thus, we hypothesized that hindbrain-directed PrRP administration would affect energy balance and motivated feeding behavior. METHODS: To address this hypothesis, a range of behavioral and physiologic variables were measured in Sprague-Dawley rats that received PrRP delivered to the fourth ventricle (4V) or the nucleus of the solitary tract (NTS) at the level of the area postrema (AP). RESULTS: 4V PrRP delivery decreased chow intake and body weight, in part, through decreasing meal size in ad libitum maintained rats tested at dark onset. PrRP inhibited feeding when delivered to the nucleus tractus solitarius (NTS), but not to more ventral hindbrain structures. In addition, 4V as well as direct NTS administration of PrRP increased core temperature. By contrast, 4V PrRP did not reduce ad libitum intake of highly palatable food or the motivation to work for or seek palatable foods. CONCLUSIONS: The dorsomedial hindbrain and NTS/AP, in particular, are sites of action in PrRP/GPR10-mediated control of chow intake, core temperature, and body weight. PMID- 29796830 TI - Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles. AB - BACKGROUND: Doxorubicin hydrochloride (DOX.HCl), an anthracycline glycoside antibiotic, exhibits low oral bioavailability due to active efflux from intestinal P-glycoprotein receptors. The oral administration of DOX remains a challenge hence; no oral formulation for DOX is marketed, till date. AIM OF THE STUDY: To improve the oral bioavailability of DOX through, preparation of a nanoformulation i.e. PEGylated-doxorubicin(DOX)-loaded-poly-lactic-co-glycolic acid (PLGA)-Nanoparticles (NPs) and to develop and validate an ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric bioanalytical method (UHPLC/ESI-QTOF-MS/MS) for plasma (Wistar rats) DOX quantification. MATERIALS AND METHODS: For chromatography, Waters ACQUITY UPLCTM along with a BEH C-18 column (2.1 mm * 100 mm; 1.7 MUm), mobile phase conditions (acetonitrile: 0.1% formic acid::1:1 v/v) and flow rate (0.20 ml/min) was used. For analyte recovery from rat plasma, a liquid-liquid extraction method (LLE), using Acetonitrile: 5 mM ammonium acetate in a ratio of 6:4 v/v at pH 3.5, was used. RESULTS: Nanoformulation with a particle size (183.10 +/- 7.41 nm), zeta potential (- 13.10 +/- 1.04 mV), drug content (42.69 +/- 1.97 ug/mg) and a spherical shape and smooth surface was developed. An elution time of 1.61 and 1.75 min along with a transition at m/z 544.42/397.27 and 528.46/321.41 were observed for DOX and internal standard (IS) Daunorubicin, respectively. In addition, a linear dynamic range with r2 >= 0.9985 over a concentration range of 1.00-2500.0 ng/ml was observed for different processes and parameters used in the study. Similarly a marked improvement i.e. 6.8 fold was observed, in PEGylated-DOX-PLGA-NPs as compared to DOX-S, in pharmacokinetics studies. CONCLUSION: The promising approach of PEGylated-DOX-PLGA-NPs may provide an alternate to intravenous therapy for better patient care. PMID- 29796833 TI - Correction to: Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. AB - Introduction 3rd Paragraph. PMID- 29796832 TI - Safety of Biologics, Including Biosimilars: Perspectives on Current Status and Future Direction. AB - In recent years, marketing of highly innovative and costly biologics improved the management of high-burden diseases such as autoimmune diseases, cancers, and chronic renal failure. Several widely prescribed biologics have recently lost or will shortly lose their patents, thus opening avenues to the marketing of a growing number of biosimilars worldwide, which are products similar in terms of quality, safety, and efficacy to already licensed reference products, thus allowing for potential savings in pharmaceutical expenditure. Numerous debates about the interchangeability between biosimilars and reference products are still ongoing, owing to concerns about potential immunogenicity raised by switching, which may cause a lack of effect and toxicity. Patients successfully treated with biologic therapy may theoretically receive biosimilars to contain costs, if reference product and related biosimilar are judged as interchangeable. However, the positions of regulatory agencies on the interchangeability and automatic substitution of biologics with biosimilars are very different. The benefit-risk profile of biosimilars has been often questioned by clinicians owing to the limited amount of pre-marketing information on clinical efficacy and safety, despite biosimilarity being based on a comparability exercise with the reference product to gain the biosimilar approval. Nevertheless, after more than 10 years of marketing from the first biosimilar approval in Europe, no proof of differences in terms of the safety profile of biosimilars and originators has been reported. In this context, post-marketing evaluation of both biologics and biosimilars safety profiles through analyses from spontaneous reporting databases and claims databases is crucial. An important issue for the pharmacovigilance of biologics concerns the traceability, indicating the brand name and batch number in spontaneous adverse drug reaction reports, but this requirement is not frequently addressed. This review aims to provide an overview of the characteristics and potential challenges in the safety profile assessment of biologics with a focus on the post-marketing setting. PMID- 29796831 TI - Prescription Opioid Fatalities: Examining Why the Healer Could be the Culprit. AB - Prescription opioid use has increased rapidly in developed countries, as have fatalities and other related adverse events. This review examines the intrinsic characteristics of opioids, including their mechanisms of action and pharmacokinetic and pharmacodynamic properties, to determine how the use of a regonised pharmacological remedy for a medically confirmed ailment could result in an accidental fatality. Opioids trigger biological processes that inhibit their own therapeutic effect. Prolonged use of opioids can result in activation of pronociceptive systems, leading to opioid-induced hyperalgesia and tolerance, while opioid metabolites can antagonise the antinociceptive action of the parent drug, also leading to opioid-induced hyperalgesia and tolerance. Pain stimulates respiration and counteracts the respiratory depression effect of opioids. Analgesia from opioids leads to loss of this protective mechanism, leading to increased risk of death due to respiratory failure. Increased patient counseling during opioid prescribing and dispensing, and limiting prescription to short-term use in non-malignant pain, may decrease the adverse effects of opioids. The vast majority of patients who unintentionally experience serious adverse events from pharmaceutical opioids do not start out as drug seekers. Even opioid use within prescribing guidelines can place some patients at risk of death and may prevent patients from seeking help for prescription opioid dependence. PMID- 29796834 TI - Computer-assisted liver graft steatosis assessment via learning-based texture analysis. AB - PURPOSE: Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. METHODS: Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was [Formula: see text]. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern ([Formula: see text]), and gray-level co-occurrence matrix ([Formula: see text]) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. RESULTS: With the best-performing feature set ([Formula: see text]) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. CONCLUSIONS: This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR. PMID- 29796835 TI - A virtual pointer to support the adoption of professional vision in laparoscopic training. AB - PURPOSE: To assess a virtual pointer in supporting surgical trainees' development of professional vision in laparoscopic surgery. METHODS: We developed a virtual pointing and telestration system utilizing the Microsoft Kinect movement sensor as an overlay for any imagine system. Training with the application was compared to a standard condition, i.e., verbal instruction with un-mediated gestures, in a laparoscopic training environment. Seven trainees performed four simulated laparoscopic tasks guided by an experienced surgeon as the trainer. Trainee performance was subjectively assessed by the trainee and trainer, and objectively measured by number of errors, time to task completion, and economy of movement. RESULTS: No significant differences in errors and time to task completion were obtained between virtual pointer and standard conditions. Economy of movement in the non-dominant hand was significantly improved when using virtual pointer ([Formula: see text]). The trainers perceived a significant improvement in trainee performance in virtual pointer condition ([Formula: see text]), while the trainees perceived no difference. The trainers' perception of economy of movement was similar between the two conditions in the initial three runs and became significantly improved in virtual pointer condition in the fourth run ([Formula: see text]). CONCLUSIONS: Results show that the virtual pointer system improves the trainer's perception of trainee's performance and this is reflected in the objective performance measures in the third and fourth training runs. The benefit of a virtual pointing and telestration system may be perceived by the trainers early on in training, but this is not evident in objective trainee performance until further mastery has been attained. In addition, the performance improvement of economy of motion specifically shows that the virtual pointer improves the adoption of professional vision- improved ability to see and use laparoscopic video results in more direct instrument movement. PMID- 29796838 TI - Imaging and Genetic Approaches to Inform Biomarkers for Anxiety Disorders, Obsessive-Compulsive Disorders, and PSTD. AB - Anxiety disorders are the most common mental health problem in the world and also claim the highest health care cost among various neuropsychiatric disorders. Anxiety disorders have a chronic and recurrent course and cause significantly negative impacts on patients' social, personal, and occupational functioning as well as quality of life. Despite their high prevalence rates, anxiety disorders have often been under-diagnosed or misdiagnosed, and consequently under-treated. Even with the correct diagnosis, anxiety disorders are known to be difficult to treat successfully. In order to implement better strategies in diagnosis, prognosis, treatment decision, and early prevention for anxiety disorders, tremendous efforts have been put into studies using genetic and neuroimaging techniques to advance our understandings of the underlying biological mechanisms. In addition to anxiety disorders including panic disorder, generalised anxiety disorder (GAD), specific phobias, social anxiety disorders (SAD), due to overlapping symptom dimensions, obsessive-compulsive disorder (OCD), and post traumatic stress disorder (PTSD) (which were removed from the anxiety disorder category in DSM-5 to become separate categories) are also included for review of relevant genetic and neuroimaging findings. Although the number of genetic or neuroimaging studies focusing on anxiety disorders is relatively small compare to other psychiatric disorders such as psychotic disorders or mood disorders, various structural abnormalities in the grey or white matter, functional alterations of activity during resting-state or task conditions, molecular changes of neurotransmitter receptors or transporters, and genetic associations have all been reported. With continuing effort, further genetic and neuroimaging research may potentially lead to clinically useful biomarkers for the prevention, diagnosis, and management of these disorders. PMID- 29796836 TI - The Severity of Spinal Cord Injury Determines the Inflammatory Gene Expression Pattern after Immunization with Neural-Derived Peptides. AB - Previous studies revealed that the intensity of spinal cord injury (SCI) plays a key role in the therapeutic effects induced by immunizing with neural-derived peptides (INDP), as severe injuries abolish the beneficial effects induced by INDP. In the present study, we analyzed the expression of some inflammation related genes (IL6, IL12, IL-1beta, IFNgamma, TNFalpha, IL-10, IL-4, and IGF-1) by quantitative PCR in rats subjected to SCI and INDP. We investigated the expression of these genes after a moderate or severe contusion. In addition, we evaluated the effect of INDP by utilizing two different peptides: A91 and Cop-1. After moderate injury, both A91 and Cop-1 elicited a pattern of genes characterized by a significant reduction of IL6, IL1beta, and TNFalpha but an increase in IL10, IL4, and IGF-1 expression. There was no effect on IL-12 and INFgamma. In contrast, the opposite pattern was observed when rats were subjected to a severe spinal cord contusion. Immunization with either peptide caused a significant increase in the expression of IL-12, IL-1beta, IFNgamma (pro inflammatory genes), and IGF-1. There was no effect on IL-4 and IL-10 compared to controls. After a moderate SCI, INDP reduced pro-inflammatory gene expression and generated a microenvironment prone to neuroprotection. Nevertheless, severe injury elicits the expression of pro-inflammatory genes that could be aggravated by INDP. These findings correlate with our previous results demonstrating that severe injury inhibits the beneficial effects of protective autoimmunity. PMID- 29796840 TI - CME instructions: Invasive assessment of coronary artery disease. PMID- 29796839 TI - Does Anhedonia Presage Increased Risk of Posttraumatic Stress Disorder? : Adolescent Anhedonia and Posttraumatic Disorders. AB - Anhedonia, the reduced ability to experience pleasure, is a dimensional entity linked to multiple neuropsychiatric disorders, where it is associated with diminished treatment response, reduced global function, and increased suicidality. It has been suggested that anhedonia and the related disruption in reward processing may be critical precursors to development of psychiatric symptoms later in life. Here, we examine cross-species evidence supporting the hypothesis that early life experiences modulate development of reward processing, which if disrupted, result in anhedonia. Importantly, we find that anhedonia may confer risk for later neuropsychiatric disorders, especially posttraumatic stress disorder (PTSD). Whereas childhood trauma has long been associated with increased anhedonia and increased subsequent risk for trauma-related disorders in adulthood, here we focus on an additional novel, emerging direct contributor to anhedonia in rodents and humans: fragmented, chaotic environmental signals ("FRAG") during critical periods of development. In rodents, recent data suggest that adolescent anhedonia may derive from aberrant pleasure/reward circuit maturation. In humans, recent longitudinal studies support that FRAG is associated with increased anhedonia in adolescence. Both human and rodent FRAG exposure also leads to aberrant hippocampal function. Prospective studies are underway to examine if anhedonia is also a marker of PTSD risk. These preliminary cross-species studies provide a critical construct for future examination of the etiology of trauma-related symptoms in adults and for and development of prophylactic and therapeutic interventions. In addition, longitudinal studies of reward circuit development with and without FRAG will be critical to test the mechanistic hypothesis that early life FRAG modifies reward circuitry with subsequent consequences for adolescent-emergent anhedonia and contributes to risk and resilience to trauma and stress in adulthood. PMID- 29796837 TI - Transcriptional Regulation Involved in Fear Memory Reconsolidation. AB - Memory reconsolidation has been demonstrated to offer a potential target period during which the fear memories underlying fear disorders can be disrupted. Reconsolidation is a labile stage that consolidated memories re-enter after memories are reactivated. Reactivated memories, induced by cues related to traumatic events, are susceptible to strengthening and weakening. Gene transcription regulation and protein synthesis have been suggested to be required for fear memory reconsolidation. Investigating the transcriptional regulation mechanisms underlying reconsolidation may provide a therapeutic method for the treatment of fear disorders such as post-traumatic stress disorder (PTSD). However, the therapeutic effect of treating a fear disorder through interfering with reconsolidation is still contradictory. In this review, we summarize several transcription factors that have been linked to fear memory reconsolidation and propose that transcription factors, as well as related signaling pathways can serve as targets for fear memory interventions. Then, we discuss the application of pharmacological and behavioral interventions during reconsolidation that may or not efficiently treat fear disorders. PMID- 29796843 TI - Robotic repair of left-sided partial anomalous pulmonary venous connection to the coronary sinus. AB - Left-sided partial anomalous pulmonary venous connection to the coronary sinus is a rare congenital cardiac defect. Surgical repair is indicated to prevent cardiopulmonary morbidities that may occur in later age. Although the conventional median sternotomy or thoracotomy incisions are used during surgical repair, robotic surgery can be a feasible alternative approach to this pathology. In this case, we report a 14-year-old child, who was diagnosed with left partial anomalous pulmonary venous connection to the coronary sinus. A total endoscopic robotic repair was successfully done via right atriotomy approach. After routing of the pulmonary venous return from the left lung to the left atrium, the interatrial septum was reconstructed with a pericardial patch. We report a successful use of totally endoscopic robotic approach in a patient diagnosed with left-sided partial anomalous pulmonary venous connection. PMID- 29796841 TI - Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients. AB - OBJECTIVES: The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R -> 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. METHODS: A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15 umol/L. RESULTS: MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p = 0.035). CONCLUSIONS: The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients. PMID- 29796842 TI - sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFkappaB-NLRP3 activation. AB - OBJECTIVE AND DESIGN: The receptor for advanced glycation endproducts (RAGE) is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that RAGE mediated signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether RAGE has a role in regulating pathological cardiac hypertrophy. MATERIALS AND SUBJECTS: Protein abundance was estimated using Western blotting and intracellular ROS level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL 1beta. All in vitro experiments were performed using H9C2 cells. TREATMENTS: To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 ug/ml sRAGE was treated 1 h prior to addition of Ang II. RESULTS: sRAGE attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating RAGE and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1beta, estimated from a cell culture medium, were significantly reduced by sRAGE. Activated PKCs and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sRAGE treatment. Furthermore, we found that nuclear factor-kappaB and NOD-like receptor protein 3 (NLRP3) were associated with RAGE-mediated cardiomyocyte hypertrophy. CONCLUSIONS: In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-kappaB-NLRP3 IL1beta signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy. PMID- 29796844 TI - Tubulocystic renal cell carcinoma: a review of literature focused on radiological findings for differential diagnosis. AB - Tubulocystic renal cell carcinoma (TC-RCC) has been classified as an independent subtype according to the 2016 World Health Organization (WHO) classification. It is a rare subtype that predominantly affects men. Although few in number, radiological imaging reports have suggested that TC-RCC is characterized by multilocular cystic lesions, which are categorized as the Bosniak classification II-IV, with signature pathological characteristics comprising numerous small cysts or a tubular structure. The Bosniak classification system facilitates patient management; however, the differentiation of cystic tumors exhibiting similar imaging findings remains impossible; in fact, the differentiation of multilocular cystic RCC, adult cystic nephroma, and mixed epithelial and stromal tumor remains challenging. This review aims to discuss TC-RCC with a focus on implications of radiological findings in the differential diagnosis of TC-RCC. PMID- 29796845 TI - Small pancreatic ductal carcinomas on triple-phase contrast-enhanced computed tomography: enhanced rims and the pathologic correlation. AB - PURPOSE: To reveal the prevalence of small (<= 20 mm) pancreatic ductal carcinomas with enhanced rims on triple-phase contrast-enhanced CT and correlate the CT images with the pathologic findings. MATERIALS AND METHODS: Between April 2005 and April 2016, 45 patients underwent preoperative triple-phase contrast enhanced CT and were pathologically diagnosed with small pancreatic ductal carcinoma. CT images were independently reviewed by two radiologists. The attenuation values of the enhanced rims, internal areas of the tumors, and surrounding pancreatic parenchyma were compared using Mann-Whitney U test. These areas were also correlated with the pathologic findings. Tumor invasiveness was compared between the tumors with and without enhanced rims using Fisher's exact test. RESULTS: Enhanced rims were identified in 18 tumors (40%) by consensus between the two reviewers. The enhanced rims showed significantly higher mean attenuation values compared with the internal areas of the tumors (p < 0.001) and surrounding pancreatic parenchyma (p < 0.0086), and were most clearly visualized on equilibrium phase. The enhanced rims pathologically reflected the abundant fibrotic stroma with cancer cells in all tumors. There was no statistically significant difference in tumor invasiveness between the tumors with and without enhanced rims (anterior peripancreatic invasion, p = 0.137; posterior peripancreatic invasion, p = 0.758; portal vein invasion, p = 0.639; and lymph node metastases, p = 0.359). CONCLUSIONS: Enhanced rims were detected at a rate of 40% in small pancreatic ductal carcinomas and could be an important finding for diagnosis on CT images, but did not suggest a less aggressive nature. PMID- 29796846 TI - Bayonet sign in dysphagia lusoria. PMID- 29796847 TI - Learning by heart-the relationship between resting vagal tone and metacognitive judgments: a pilot study. AB - Metacognitive awareness and resting vagally mediated heart rate variability (HRV) as a physiological trait marker of cognitive inhibitory control capacities are both associated with better well-being and seem to share a common neural basis. Executive functioning which is considered a prerequisite for delivering prospective metacognitive judgments has been found to be correlated with HRV. This pilot study addresses the question, whether metacognitive awareness and resting vagally mediated HRV are positively associated. A sample of 20 healthy participants was analyzed that completed a typical Judgment of Learning task after an electrocardiogram had been recorded. The root-mean-squares of successive differences were used to calculate vagally mediated HRV. Metacognitive awareness was measured by comparing the judgments of learning with the actual memory performance, yielding a deviation score. HRV was found to be positively correlated with metacognitive awareness. Results suggest that metacognitive abilities might relate to physiological trait markers of cognitive inhibitory control capacities. Further experimental studies are needed to investigate causal relations. PMID- 29796848 TI - Comparison of complete versus partial mesh removal for the treatment of chronic mesh infection after abdominal wall hernia repair. AB - PURPOSE: Treatment of chronic mesh infections (CMI) after parietal repair is difficult and not standardized. Our objective was to present the results of a standardized surgical treatment including maximal infected mesh removal. METHODS: Patients who were referred to our center for chronic mesh infection were analyzed according to CMI risk factors, initial hernia prosthetic cure, CMI characteristics and treatments they received to achieve a cure. RESULTS: Thirty four patients (mean age 54 +/- 13 years; range 23-72), were included. Initial prosthetic cure consisted of 26 incisional hernias and eight groin or umbilical hernias of which 21% were considered potentially contaminated because of three intestinal injuries, two stomas and two strangulated hernias. The mesh was synthetic in all cases. CMI appeared after a mean of 83 days (range 30-6740) and was characterized by chronic leaking in 52 cases (50%), an abscess in 22 cases (21%) and synchronous hernia recurrence in 17 cases (16.5%). Eighty-six reinterventions were necessary, including 36 mesh removals (42%), and 13 intestinal resections for entero-cutaneous fistula (15%). The CMI persistence rate was 81% (35 reinterventions out of 43) when mesh removal was voluntarily limited to infected and/or not incorporated material, but was 44% when mesh removal was voluntarily complete (19 reinterventions out of 43; p < 0.001). On average, 3.4 interventions (1-11) were necessary to achieve a cure, after 2.8 years (0-6). Fourteen incisional hernia recurrences occurred (41%). CONCLUSIONS: Treatment of chronic mesh infection is lengthy and resource-intensive, with a high risk of hernia recurrence. Maximal mesh removal is mandatory. PMID- 29796850 TI - Inpatient use and area-level socio-environmental factors in people with psychosis. AB - PURPOSE: There is consistent evidence that socio-environmental factors measured at an area-level, such as ethnic density, urban environment and deprivation are associated with psychosis risk. However, whether area-level socio-environmental factors are associated with outcomes following psychosis onset is less clear. This study aimed to examine whether the number of inpatient days used by people presenting to mental health services for psychosis was associated with five key area-level socio-environmental factors: deprivation, ethnic density, social capital, population density and social fragmentation. METHODS: Using a historical cohort design based on electronic health records from the South London and Maudsley NHS Trust Foundation electronic Patient Journey System, people who presented for the first time to SLAM between 2007 and 2010 with psychosis were included. Structured data were extracted on age at presentation, gender, ethnicity, residential area at first presentation and number of inpatient days over 5 years of follow-up. Data on area-level socio-environmental factors taken from published sources were linked to participants' residential addresses. The relationship between the number of inpatient days and each socio-environmental factor was investigated in univariate negative binomial regression models with time in contact with services treated as an offset variable. RESULTS: A total of 2147 people had full data on area level outcomes and baseline demographics, thus, could be included in the full analysis. No area-level socio-environmental factors were associated with inpatient days. CONCLUSION: Although a robust association exists between socio-environmental factors and psychosis risk, in this study we found no evidence that neighbourhood deprivation was linked to future inpatient admissions following the onset of psychosis. Future work on the influence of area level socio-environmental factors on outcome should examine more nuanced outcomes, e.g. recovery, symptom trajectory, and should account for key methodological challenges, e.g. accounting for changes in address. PMID- 29796849 TI - The association of depression and posttraumatic stress disorder with the metabolic syndrome in a multi-ethnic cohort: the HELIUS study. AB - PURPOSE: Depression and posttraumatic stress disorder (PTSD) may be linked to the metabolic syndrome (MetS). Consistency of this association across ethnic groups and the influence of comorbidity of depression/PTSD were examined. METHODS: Cross sectional baseline data from the HELIUS study were used (4527 Dutch, 2999 South Asian Surinamese, 4058 African Surinamese, 2251 Ghanaian, 3522 Turkish and 3825 Moroccan participants). The Patient Health Questionnaire-9 (PHQ-9) (score range 0 27) measured depressive symptoms. A 9-item questionnaire (score range 0-9) measured PTSD symptoms. The MetS was defined according to the International Diabetes Federation. The association of a depressed mood (PHQ-9 sum score >= 10) and severe PTSD symptoms (sum score >= 7) with the MetS was examined using logistic regression. Interaction with ethnicity and between a depressed mood and severe PTSD symptoms was tested. RESULTS: A depressed mood was associated with the MetS [OR (95% CI) = 1.37 (1.24-1.51)] in the total sample and consistent across ethnic groups (p values for interaction all > 0.05). Severe PTSD symptoms were significantly associated with the MetS in the Dutch [OR (95% CI) = 1.71 (1.07-2.73)]. The South-Asian Surinamese, Turks and Moroccans showed weaker associations than the Dutch (p values for interaction all < 0.05). A depressed mood and severe PTSD symptoms did not interact in the association with the MetS (p values for interaction > 0.05). CONCLUSIONS: A depressed mood was consistently associated with the MetS across ethnic groups, but the association between severe PTSD symptoms and the MetS maybe ethnicity dependent. The association with the MetS was not different in case of depressed mood/severe PTSD symptoms comorbidity. PMID- 29796851 TI - A hyaluronic acid- and chondroitin sulfate-based medical device improves gastritis pain, discomfort, and endoscopic features. AB - Gastritis is an inflammation of the gastric mucosa. In this study, we investigated the efficacy of a medical device, Esoxx(r), based on hyaluronic acid and chondroitin sulfate on gastritis-related upper abdominal pain/discomfort and endoscopic features. Fifty patients, affected by gastritis, were randomised to receive the medical device or placebo. The primary endpoint was the medical device efficacy on upper abdominal pain/discomfort associated with gastritis and measured by Visual Analogue Scale (VAS). The secondary endpoints were the efficacy of the medical device on gastritis-related mucosal erosions, blood oozing, and hyperemia (redness)/edema, as assessed by endoscopy, and the patients' rating of their compliance with the treatments. A significant reduction in VAS pain was observed in the treatment group after a 5-week treatment, if compared with placebo (p < 0.001). In summary, administration of a medical device, based on hyaluronic acid and chondroitin sulfate, improves gastritis related upper abdominal pain/discomfort and decreases mucosal erosions, blood oozing, and hyperemia (redness)/edema at 5-week follow-up in patients affected by gastritis. PMID- 29796852 TI - The Draft Genome Sequence of Clostridium sp. Strain NJ4, a Bacterium Capable of Producing Butanol from Inulin Through Consolidated Bioprocessing. AB - A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP. PMID- 29796853 TI - A Real-Time PCR with Melting Curve Analysis for Molecular Typing of Vibrio parahaemolyticus. AB - Foodborne disease caused by Vibrio parahaemolyticus is a serious public health problem in many countries. Molecular typing has a great scientific significance and application value for epidemiological research of V. parahaemolyticus. In this study, a real-time PCR with melting curve analysis was established for molecular typing of V. parahaemolyticus. Eighteen large variably presented gene clusters (LVPCs) of V. parahaemolyticus which have different distributions in the genome of different strains were selected as targets. Primer pairs of 18 LVPCs were distributed into three tubes. To validate this newly developed assay, we tested 53 Vibrio parahaemolyticus strains, which were classified in 13 different types. Furthermore, cluster analysis using NTSYS PC 2.02 software could divide 53 V. parahaemolyticus strains into six clusters at a relative similarity coefficient of 0.85. This method is fast, simple, and conveniently for molecular typing of V. parahaemolyticus. PMID- 29796855 TI - Editorial. PMID- 29796854 TI - Breast cancer metastasis through the lympho-vascular system. AB - Breast cancer metastasizes through the lymphovascular system to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Renewed interest in the route by which tumor cells gain access to blood and lymphatic capillaries are the subject of research at mechanical, anatomic, pathologic, genetic, epidemiologic and molecular levels. Two papers presented at the 7th International Symposium on Cancer Metastasis in San Francisco showed tumor cells entering the systemic circulation through the sentinel lymph node. This information challenges the current paradigm where clinicians believe that access is gained through intra- and peri-tumoral blood vessels and that metastasis to axillary lymph nodes is an interesting epi-phenomenon. The sentinel lymph node era has changed the modern surgical approach to the axilla and the basis of this change is summarized in this paper. A new approach to the management of axillary metastases after systemic therapy relies on determining whether there is a complete pathologic response; if no tumor is found in the previously biopsied node, a complete axillary lymph node dissection may be avoided. African American women seem to inherit a trait from West African ancestors and tend to develop more lethal types of breast cancer. These tumors may have a molecular machinery that enhances their ability to metastasize to visceral sites and future research may unearth the mechanisms for this phenomenon. PMID- 29796856 TI - Impact of ischaemia-reperfusion cycles during ischaemic preconditioning on 2000-m rowing ergometer performance. AB - PURPOSE: Although ischaemic preconditioning (IPC), induced by cycles of transient limb ischaemia and reperfusion, seems to improve exercise performance, the optimal duration of ischaemia-reperfusion cycles is not established. The present study investigated the effect of ischaemia-reperfusion duration within each IPC cycle on performance in a 2000-m rowing ergometer test. METHODS: After incremental and familiarization tests, 16 trained rowers (mean +/- SD: age, 24 +/ 11 years; weight, 74.1 +/- 5.9 kg; [Formula: see text] peak, 67.2 +/- 7.4 mL.kg 1.min-1) were randomly submitted to a 2000-m rowing test preceded by intermittent bilateral cuff inflation of the lower limbs with three cycles of ischaemia reperfusion, lasting 5 min (IPC-5) or 10 min (IPC-10) at 220 or 20 mmHg (control). Power output, [Formula: see text], heart rate, blood lactate concentration, pH, ratings of perceived exertion (RPE), and near-infrared spectroscopy-derived measurements of the vastus lateralis muscle were continuously recorded. RESULTS: No differences among treatments were found in the 2000-m test (control: 424 +/- 17; IPC-5: 425 +/- 16; IPC-10: 424 +/- 17 s; P = 0.772). IPC-10 reduced the tissue saturation index and oxy-haemoglobin concentration during exercise compared with control. The power output during the last 100-m segment was significantly lower with IPC-10. The IPC treatments increased the heart rate over the first 500 m and decreased the pH after exercise. No alterations were observed in [Formula: see text], blood lactate, or RPE among the trials. CONCLUSION: In conclusion, IPC does not improve the 2000-m rowing ergometer performance of trained athletes regardless of the length of ischaemia-reperfusion cycles. PMID- 29796859 TI - Reply to Letter to the Editor "The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo controlled clinical trial". PMID- 29796857 TI - Cross-education does not accelerate the rehabilitation of neuromuscular functions after ACL reconstruction: a randomized controlled clinical trial. AB - PURPOSE: Cross-education reduces quadriceps weakness 8 weeks after anterior cruciate ligament (ACL) surgery, but the long-term effects are unknown. We investigated whether cross-education, as an adjuvant to the standard rehabilitation, would accelerate recovery of quadriceps strength and neuromuscular function up to 26 weeks post-surgery. METHODS: Group allocation was randomized. The experimental (n = 22) and control (n = 21) group received standard rehabilitation. In addition, the experimental group strength trained the quadriceps of the non-injured leg in weeks 1-12 post-surgery (i.e., cross education). Primary and secondary outcomes were measured in both legs 29 +/- 23 days prior to surgery and at 5, 12, and 26 weeks post-surgery. RESULTS: The primary outcome showed time and cross-education effects. Maximal quadriceps strength in the reconstructed leg decreased 35% and 12% at, respectively, 5 and 12 weeks post-surgery and improved 11% at 26 weeks post-surgery, where strength of the non-injured leg showed a gradual increase post-surgery up to 14% (all p <= 0.015). Limb symmetry deteriorated 9-10% more for the experimental than control group at 5 and 12 weeks post-surgery (both p <= 0.030). One of 34 secondary outcomes revealed a cross-education effect: Voluntary quadriceps activation of the reconstructed leg was 6% reduced for the experimental vs. control group at 12 weeks post-surgery (p = 0.023). Both legs improved force control (22-34%) and dynamic balance (6-7%) at 26 weeks post-surgery (all p <= 0.043). Knee joint proprioception and static balance remained unchanged. CONCLUSION: Standard rehabilitation improved maximal quadriceps strength, force control, and dynamic balance in both legs relative to pre-surgery but adding cross-education did not accelerate recovery following ACL reconstruction. PMID- 29796860 TI - Effect of resveratrol in type 2 diabetes oxidative stress markers: a reassessment. PMID- 29796861 TI - Acute femoral shortening for reconstruction of a complex lower extremity crush injury. AB - Traumatic through-knee or transfemoral amputations with concomitant ipsilateral femoral fractures are extremely rare injuries. The initial goal of management is patient resuscitation and stabilization. Subsequent interventions focus on limb salvage and the creation of a residual limb that can be fitted successfully for a functional lower extremity prosthesis. We present the case of a patient who sustained a traumatic through-knee amputation ipsilateral to an open comminuted femoral fracture. Soft tissue injury prohibited initial primary closure over the distal femoral condyles. A functional residual limb was achieved with acute femoral shortening, maintenance of the femoral condyles and fracture stabilization with a short retrograde intramedullary nail. This approach allowed maintenance of muscular attachments to the femur, soft tissue closure and resulted in a residual limb of acceptable length with a broad weight-bearing surface that was fitted with a prosthesis successfully. PMID- 29796858 TI - Intermittent versus constant aerobic exercise in middle-aged males: acute effects on arterial stiffness and factors influencing the changes. AB - PURPOSE: Both constant and intermittent acute aerobic exercises have been found to decrease arterial stiffness. However, direct comparisons of these two types of exercise are sparse. It is not known which type of exercise has the greatest effect. METHODS: We evaluated the haemodynamic responses in 15 males (age 48.5 +/ 1.3 years; BMI 27.5 +/- 0.8 kg m-2) following acute constant (CE) and intermittent cycling exercise (IE). Duration and heart rate were matched during both exercises (131.8 +/- 3.2 bpm for CE and 132.0 +/- 3.1 bpm for IE). Central and peripheral arterial stiffness was assessed through pulse wave velocity (PWV). Plasma concentrations of nitric oxide (NO), atrial natriuretic peptide (ANP), blood lactate, noradrenaline, and adrenaline were measured before and after each exercise. RESULTS: Central (+ 1.8 +/- 7.4 and - 6.5 +/- 6.8% for CE and IE) and upper limb PWV (+ 2.7 +/- 6.2 and - 8 +/- 4.6% for CE and IE) were not significantly altered although a small decrease (small effect size) was observed after IE. However, lower limb PWV significantly decreased after exercises (- 7.3 +/- 5.7 and - 15.9 +/- 4% after CE and IE), with a larger effect after IE. CONCLUSIONS: Greater decrease in lower limb PWV occurred after IE despite greater heart rate. This may be due to the higher blood levels of lactate during IE, while NO, ANP, noradrenaline, and adrenaline levels remained not statistically different from CE. These results underlined the importance of lactate in triggering the post-exercise vascular response to exercise, as well as its regional characteristic. PMID- 29796863 TI - Chronic Urticaria: Comparisons of US, European, and Asian Guidelines. AB - PURPOSE OF REVIEW: Chronic urticaria is a common dermatological condition that has significant impact on quality of life. Multiple international societies have published guidelines, and although these guidelines generally agree on the definition of urticaria, as well as approach to diagnosis and management, there have been notable differences to date. These differences have been reconciled by the recent publication of the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO. RECENT FINDINGS: The 2017 revision and update to the guidelines for chronic urticaria are the most comprehensive consensus document to date, and reconcile previously existing differences between the US, European, and Asian guidelines. The purpose of our review is to present basic background on urticaria and discuss classification, diagnosis, and most importantly, management. We present differences from previous US, European, and Asian guidelines and reconcile the previous differences by summarizing the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO. PMID- 29796862 TI - Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis. AB - Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p = 0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC. PMID- 29796864 TI - Multinomial models reveal deficits of two distinct controlled retrieval processes in aging and very mild Alzheimer disease. AB - Dual-process models of episodic retrieval reveal consistent deficits of controlled recollection in aging and Alzheimer disease (AD). In contrast, automatic familiarity is relatively spared. We extend standard dual-process models by showing the importance of a third capture process. Capture produces a failure to attempt recollection, which might reflect a distinct error from an inability to recollect when attempted (Jacoby et al. Journal of Experimental Psychology: General, 134(2), 131-148, 2005a). We used multinomial process tree (MPT) modeling to estimate controlled recollection and capture processes, as well as automatic retrieval processes, in a large group of middle-aged to older adults who were cognitively normal (N = 519) or diagnosed with the earliest detectable stage of AD (N = 107). Participants incidentally encoded word pairs (e.g., knee bone). At retrieval, participants completed cued word fragments (e.g., knee b_n_) with primes that were congruent (e.g., bone), incongruent (e.g., bend), or neutral (i.e., &&&) to the target (e.g., bone). MPT models estimated retrieval processes both at the group and the individual levels. A capture parameter was necessary to fit MPT models to the observed data, suggesting that dual-process models of this task can be contaminated by a capture process. In both group- and individual-level analyses, aging and very mild AD were associated with increased susceptibility to capture, decreased recollection, and no differences in automatic influences. These results suggest that it is important to consider two distinct modes of attentional control when modeling retrieval processes. Both forms of control (recollection and avoiding capture) are particularly sensitive to cognitive decline in aging and early-stage AD. PMID- 29796866 TI - The effects of ultrasound-guided corticosteroid injection compared to oxygen ozone (O2-O3) injection in patients with knee osteoarthritis: a randomized controlled trial. AB - Osteoarthritis (OA) is a chronic multifactorial disease characterized by progressive joint degeneration. The purpose of this study was to compare the effects of ultrasound-guided corticosteroid injection with oxygen-ozone injection in patients with knee OA. This double-blind randomized clinical trial was performed on 62 patients with knee OA. The patients were randomly divided into two groups. In the first group 40 mg triamcinolone (1 cc) and in the second group 10 cc (15 MUg/ml) oxygen-ozone (O2-O3) were injected into the knee joint under ultrasound guidance. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC), knee flexion range of motion (ROM), effusion in ultrasound images of the suprapatellar recess, and visual analog scale (VAS), which were evaluated before injection, 1 week, 1 month, and 3 months after the treatment. Sixty-two patients (10 men and 52 women) were enrolled with mean age of 57.9 years. VAS improved in both groups (steroid P value = 0.001, oxygen-ozone P value > 0.001). The improvements seen in VAS and WOMAC scores 3 months after treatment were in favor of the oxygen-ozone group when compared to the steroid group (P = 0.041 vs P = 0.19). There was no significant difference between the two groups in ROM and joint effusion seen under ultrasound (ROM p = 0.880, effusion p = 0.362). However, in the oxygen-ozone-receiving group, joint effusion was decreased significantly (p < 0.001). Both steroid and oxygen-ozone injections are effective in patients with knee osteoarthritis. Our study showed that the effects of oxygen-ozone injection last longer than those of steroid injection to the knee joint. PMID- 29796865 TI - Evaluation of gray matter perfusion in episodic migraine using voxel-wise comparison of 3D pseudo-continuous arterial spin labeling. AB - BACKGROUND: Although previous studies have demonstrated that structural and functional abnormalities in episodic migraine (EM), less is known about altered brain perfusion in the EM. The aim of this study is to investigate altered gray matter perfusion in EM using a 3D volumetric perfusion imaging. METHODS: Fifteen EM patients and 15 normal controls (NC) underwent structural and 3D pseudo continuous arterial spin labeling (3D pc-ASL). The structural images were segmented using DARTEL methods and the generated normalized T1 tissue probability maps were used to coregister the cerebral blood flow (CBF) images, which would further be performed with standardization using Fisher Z Transformation. Voxel wise analysis was applied to CBF map with Z standardization, and the Z value of the abnormal brain region was extracted and performed with correlation with the clinical variables. RESULTS: The increased CBF value located in the left Brodmann 38 (BA38) and no significantly decreased CBF value were detected in EM. HAMD scores presented significantly positive correlation with the CBF value of the left BA38. CONCLUSION: The current study indicated that the pattern of cerebral hyperperfusion may elucidate the neurogenic mechanism in the EM genesis, and 3D pc-ASL technique would non-invasively provide valuable cerebral perfusion information for the further pathophysiological and neuropsychological study in EM. PMID- 29796868 TI - [Erratum to: Holistic approach for understanding and treatment of chronic pain in old age]. PMID- 29796867 TI - [Preoperative risk identification using the Identification of Seniors at Risk? : Suitability as sole screening tool for inpatient aged risk patients]. AB - BACKGROUND: As more aged patients are surgically treated in hospitals without specialized geriatric care, patients at risk for perioperative complications must be identified and treatment must be adapted. The aim was the use of the Identification of Seniors at Risk (ISAR) as a screening tool for the identification of high-risk patients, who need specialized perioperative care. The study presented investigated the use of ISAR screening not only as recommended in the emergency room but also in validation tests as a new option in elective surgery. MATERIAL AND METHODS: Routine data recorded during inpatient admission of 389 patients were evaluated retrospectively. The ISAR as well as a cognitive screening with the mini mental state examination (MMSE) were conducted in patients as long as a previously diagnosed dementia was not present. Delirium was recorded using the Confusion Assessment Method (CAM). A total of 88 patients from trauma surgery served as an example for emergency surgery and 93 patients from orthopedics for elective surgery. All patients received treatment by the department of Anesthetic and Perioperative Geriatric Care. RESULTS: According to an ISAR score of >=2 points, 85.2% of traumatology and 48.4% of elective orthopedic patients were considered to be geriatric high-risk patients. Among ISAR negative patients many suffered from preoperative cognitive decline (MMST or diagnosed dementia), especially in the elective orthopedics group. Delirium occurred in 5.7% of trauma surgery patients and in 4.3% of elective orthopedic patients. CONCLUSION: With 2 as a cut-off, the use of ISAR as a screening tool was only conditionally suitable. In particular, the expected filter function was not fulfilled in both groups. PMID- 29796870 TI - [Clinical hematological symptoms of vitamin B12 deficiency in old age : Summarized overview of this year's symposium of the Working Group "Anemia in the Aged" on the occasion of the annual conference of the German Geriatric Society (DGG) in Frankfurt]. AB - The interdisciplinary symposium of the working group "anemia in the aged" on the occasion of the annual conference of the German Society of Geriatrics focused this year on vitamin B12 deficiency in aged patients. Experts from hematopathology, clinical geriatrics and geriatric hematology presented the case of a 78-year-old woman and an interdisciplinary discussion was held on the epidemiology, clinical aspects as well as diagnostic and therapeutic steps. This article reviews the symposium on vitamin B12 deficiency in the aged in the context of the currently available literature. PMID- 29796869 TI - [Operative risk of geriatric patients in cardiac surgery]. AB - BACKGROUND: Despite substantial progress in interventional cardiology, there are still many geriatric patients who require cardiac surgery. Estimation of the operative risk is therefore of great importance. OBJECTIVE: The prognostic value of the geriatric assessment for estimation of the operative risk was evaluated. MATERIAL AND METHODS: Between 2008 and 2009 a geriatric assessment was carried out on 500 patients before an urgent or elective cardiac surgery intervention. The primary endpoints were in-hospital death, death within 30 days after the intervention and stroke. A secondary endpoint was the combination of death, stroke and in-hospital complications. RESULTS: The average age of the patients was 77.1 +/- 4.6 years and 44.3% of the particpants were women. Aortic stenosis was the primary reason for surgery in 49.2% of patients and coronary artery disease in 38.8% of patients. Half of the patients (56.5%) showed functional impairments in one or more evaluated domains. Significant limitations in cognitive function were present in 11.8% and in mobility in 2.4% of the patients. The 30-day mortality was 2.9% and stroke occurred in 1.4% of the patients. After multivariate analysis cognitive impairment remained independently associated with the operative mortality (odds ratio OR 3.8, 95% confidence interval CI 1.2-12.7). CONCLUSION: The perioperative mortality of older patients in cardiac surgery is low. A limited functional status detected in the geriatric assessment is associated with an increased mortality. Impaired cognitive function is an independent predictor of postoperative mortality. PMID- 29796872 TI - Screening Mammography: Getting to Version 2.0. PMID- 29796873 TI - Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells. AB - Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically. PMID- 29796874 TI - Prevalence of use of antipsychotic drugs in the elderly in Catalonia. PMID- 29796875 TI - Organochlorine Chemical Residues in Northern Cardinal (Cardinalis cardinalis) Eggs from Greater Washington, DC USA. AB - Northern Cardinal eggs from six neighborhoods near Washington DC were analyzed for organochlorine pesticides and PCBs. All compounds were detected more frequently and at higher concentrations in more heavily urbanized neighborhoods. DDT (mostly as p,p'-DDE) was detected in all neighborhoods. p,p'-DDT was typically 0.5-16 ng/g (ww) in most suburban neighborhoods but was not detected (< 0.1 ng/g) in more rural areas; however, p,p'-DDT was 127-1130 ng/g in eggs from two suburban Maryland nests and comprised 65.7% of total p,p'-DDT isomers in the most contaminated sample, indicating recent exposure to un-weathered DDT. Total chlordane (sum of 5 compounds) was 2-70 ng/g; concentrations were greatest in older suburban neighborhoods. Total PCB (sum of detected congeners) was < 5-21 ng/g. Congener patterns were similar in all neighborhoods and resembled those typical of weathered mixtures. Results indicate that wildlife remains exposed to low concentrations of legacy contaminants in suburban neighborhoods and that cardinal eggs can be used to monitor localized contamination. PMID- 29796878 TI - Natural Deep Eutectic Solvents and Their Applications in Biotechnology. AB - Following the appearance of ionic liquids (ILs) and deep eutectic solvents (DESs), natural deep eutectic solvents (NADESs) have emerged as a new type of truly green solvents with many excellent advantages such as cheapness, sustainability, biocompatibility, environmental friendliness, and, in particular, remarkable solubilizing power and outstanding designability. Although only at an early stage, research on NADESs has started to blossom with exponential growth, showing attractive and promising potentials for applications in various areas. In this chapter we focus on an introduction to what is currently known about NADESs: their formation, structure and roles in nature, their physical/chemical properties, their toxicity and biodegradability, and, more importantly, their beneficial applications in biotechnology. PMID- 29796877 TI - Synthesis of beta-Peptide Standards for Use in Model Prebiotic Reactions. AB - A one-pot method was developed for the preparation of a series of beta-alanine standards of moderate size (2 to >=12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of beta-alanine methyl ester, yielding beta-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of beta-alanine peptide methyl ester oligomers, producing a series of beta-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of beta-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of beta-peptide standards for investigating differences between alpha- and beta-peptides in the context of prebiotic chemistry. PMID- 29796876 TI - De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies. AB - Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies. PMID- 29796879 TI - Impacts of supplementing growing rabbit diets with whey powder and citric acid on growth performance, nutrient digestibility, meat and bone analysis, and gut health. AB - The present study evaluated the impact of supplementing the rabbit diet with graded levels of whey powder and citric acid. The dietary treatments were as follows: T1, control diet (basal diet); T2, basal diet + 10 g/kg citric acid; T3, T2 + whey powder (7.5 g/kg); T4, T2 + whey powder (15 g/kg); and T5, T2 + whey powder (22.5 g/kg). Results, the T5 diet resulted in the best (P < 0.05) final body weight, body weight gain, feed conversion ratio, protein efficiency, relative growth rate, and dressed weight. The best (P < 0.05) digestion coefficients were associated with the T4 and T5 diets. Rabbits fed diets supplemented with citric acid alone or with addition of graded levels of whey powder showed significantly lower (P < 0.05) intestinal pH than those fed the T1 diet. The T4 and T5 diets resulted in greater CP and ash in the thigh muscle compared with the T1 and T2 diets. Calcium content in the femur bone was higher (P < 0.05) in the T5 group followed by T4 and T3. The wall of different parts of the small intestine improved in the T4 and T5 groups, showing the greatest increase in the small intestinal villi, intestinal glands, and amount of goblet cells. In conclusion, addition of whey powder (1.5, and 2.25%) increased the growth performance, nutrient digestibility and crude protein content of the thigh muscle, and improved the gut health of growing rabbits and the best level was 2.25% whey powder. Citric acid addition had no positive effect on growth performance, nutrient digestibility, crude protein content of the thigh muscle, and the gut health. PMID- 29796880 TI - Micro-scale pollution mechanism of dust diffusion in a blasting driving face based on CFD-DEM coupled model. AB - In order to investigate the diffuse pollution mechanisms of high-concentration dusts in the blasting driving face, the airflow-dust coupled model was constructed based on CFD-DEM coupled model; the diffusion rules of the dusts with different diameters at microscopic scale were analyzed in combination with the field measured results. The simulation results demonstrate that single-exhaust ventilation exhibited more favorable dust suppression performance than single forced ventilation. Under single-exhaust ventilation condition, the motion trajectories of the dusts with the diameter smaller than 20 MUm were close to the airflow streamline and these dusts were mainly distributed near the footway walls; by contrast, under single-forced ventilation condition, the motion trajectories of the dust particles with a diameter range of 20~40 MUm were close to the airflow streamlines, and a large number of dusts with the diameter smaller than 20 MUm accumulated in the regions 5 m and 17~25 m away from the head-on section. Moreover, under the single-exhaust ventilation, the relationship between dust diameter D and negative-pressured-induced dust emission ratio P can be expressed as P = - 25.03ln(D) + 110.39, and the dust emission ratio was up to 74.36% for 7-MUm dusts, and the path-dependent settling behaviors of the dusts mainly occurred around the head-on section; under single-forced ventilation condition, the z value of the dusts with the diameter over 20 MUm decreased and the dusts with a diameter smaller than 7 MUm are particularly harmful to human health, but their settling ratios were below 22.36%. Graphical abstract The airflow-dust CFD-DEM coupling model was established. The numerical simulation results were verified. The migration laws of airflow field were obtained in a blasting driving face. The diffusion laws of dusts were obtained after blasting. PMID- 29796881 TI - Antimicrobial resistance and the presence of extended-spectrum beta-lactamase genes in Escherichia coli isolated from the environment of horse riding centers. AB - The aim of the study was to determine the antimicrobial resistance profile and the occurrence of extended-spectrum beta-lactamase genes and to analyze the genetic diversity of Escherichia coli strains isolated from the environment of horse riding centers. The study was conducted using E. coli strains isolated from the air, manure, and horse nostril swabs in three horse riding centers differing in the system of horse keeping-stable (OJK Pegaz and KJK Szary) and free-range (SKH Nielepice). Resistance to antibiotics was determined using the disk diffusion method, and the PCR technique was employed to detect the extended spectrum beta-lactamase (ESBL) genes, while the genetic diversity of strains was assessed by rep-PCR. A total of 200 strains were collected during the 2-year study, with the majority isolated from KJK Szary, while the smallest number was obtained from SKH Nielepice. The strains were mostly resistant to ampicillin, aztreonam, and ticarcillin. The tested strains were most frequently resistant to one or two antibiotics, with a maximum of ten antimicrobials at the same time. Two multidrug-resistant (MDR) strains were detected in OJK Pegaz while in KJK Szary there were two MDR and one extensively drug-resistant (XDR) strain. The ESBL mechanism was most frequently observed in OJK Pegaz (20.31% of strains) followed by KJK Szary (15.53% of strains) and SKH Nielepice (15.15% of strains). Among the ESBL-determining genes, only blaTEM and blaCTXM-9 were detected-blaTEM was mostly found in KJK Szary (53.40% of strains), while the second detected gene blaCTXM-9-was most frequent in SKH Nielepice (6.06% of strains). The rep-PCR genotyping showed high variation among the analyzed strains, whereas its degree differed between the studied facilities, indicating that the type of horse keeping (stable vs. free-range) affects the genetic diversity of the E. coli strains. Having regard to the fact that the tested strains of E. coli were derived from non-hospitalized horses that were not treated pharmacologically, we can assume that the observed antimicrobial resistance may be of both-natural origin, i.e., not the result of the selection pressure, and acquired, the source of which could be people present in the horse riding facilities, the remaining horses which were not included in the study, and air, as well as water, fodder, and litter of the animals. Therefore, it can be concluded that the studied horses are the source of resistant E. coli and it is reasonable to continue monitoring the changes in antimicrobial resistance in those bacteria. PMID- 29796882 TI - Aquatic plant debris changes sediment enzymatic activity and microbial community structure. AB - The retention of aquatic plant debris in freshwater systems favors a reduction in soluble reactive phosphorus (P) in overlying water through microbe-mediated mechanisms in sediment. For a more complete view of the changes in sediment microbial structure and functioning when receiving plant debris, the enzyme activities and microbial community structure in sediments incubated with or without plant debris were investigated. Significantly higher fluorescein diacetate (FDA) hydrolysis, alkaline phosphatase, polyphenol oxidase, cellulase, beta-glucosidase, and dehydrogenase activities were observed with plant debris treatment. High-throughput pyrosequencing showed that the number of total operational taxonomic units (OTUs) of bacteria estimated by using the Chao1 analysis was 2064 (in the control) and 1821 (with the plant debris treatment). The Shannon index, functional organization, and Venn diagrams revealed that the enriched OTUs in plant debris-treated community were less diversified than those in the control sample. The prominent bacterial phyla Firmicutes and Bacteroidetes were more diverse after plant debris addition. At the class level, the relative abundance of Alphaproteobacteria increased by 114% when plant debris was added, whereas the relative abundances of Beta-, Delta-, and Gammaproteobacteria decreased by 42, 78, and 86%, respectively. Azospirillum and Dechloromonas, the dominant phylogenetic groups at the genus level, increased with plant debris addition. Our study showed the importance of the above microbial genera in plant debris-mediated P retention in sediment. PMID- 29796883 TI - Co-digestion of sewage sludge with crude or pretreated glycerol to increase biogas production. AB - Anaerobic co-digestion of sewage sludge and glycerol from the biodiesel industry was evaluated in three experimental stages. In the first step, the addition of higher proportions of crude glycerol (5-20% v/v) to the sludge was evaluated, and the results showed a marked decrease in pH and inhibition of methane production. In the second step, co-digestion of sludge with either a lower proportion (1% v/v) of crude glycerol or glycerol pretreated to remove salinity resulted in volatile acid accumulation and low methane production. The accumulation of volatile acids due to the rapid degradation of glycerol in the mixture was more detrimental to methanogenesis than the salinity of the crude glycerol. In the third step, much lower amounts of crude glycerol were added to the sludge (0.3, 0.5, 0.7% v/v), resulting in buffering of the reaction medium and higher methane production than in the control (pure sludge). The best condition for co-digestion was with the addition of 0.5% (v/v) crude glycerol to the sewage sludge, which equals 0.6 g glycerol/g volatile solids applied. Under this condition, the specific methane production (mL CH4/g volatile solids applied) was 1.7 times higher than in the control. PMID- 29796885 TI - Investigating the driving forces of China's carbon intensity based on a dynamic spatial model. AB - In extant literature on China's carbon intensity, economic growth is considered an important determinant. However, the corresponding policy implications are slightly weak in subsequent practice because economic growth is an outcome of many economic activities, such as technological progress and capital stock accumulation. Furthermore, spatial spillover effects are ignored when using regional datasets. As a result, this study uses the dynamic spatial model to analyze the driving forces of China's provincial carbon intensity over the period 2000-2014. Results indicate that both technological progress and capital stock accumulation are important measures to carbon intensity reduction. China's current industrialization, urbanization, and special energy structure exert a negative effect on the decline in carbon intensity. In addition, China's provincial carbon intensity also exhibits considerable spatiotemporal distribution characteristics. As such, the corresponding policy measures are presented. PMID- 29796884 TI - Short-term effects of particle size fractions on lung function of late adolescents. AB - Although ambient air pollution has been linked to reduced lung function in healthy students, longitudinal studies that compare the response of asthmatic and healthy adolescents are lacking. To evaluate lung function responses to short term ambient air particulate matter (PM10, PM2.5, and PM1) levels, we conducted a study on high school students aged 15-18 years. The aim of this study was to assess effects of acute exposure to ambient air particulate matter (PM) on lung function in healthy and asthmatic late adolescents. We examined associations of lung function indices and ambient PM levels in 23 asthmatic and 23 healthy students. Paired-samples T test was used to evaluate the association of exposure to airborne PM concentrations with lung function test results (FVC, FEV1, FEV1/FVC, and FEF25-75). We observed negative impact of exposure to an increased concentration of ambient air PM10, PM2.5, and PM1 on lung function parameters of asthmatic and healthy late adolescents. These findings are consistent with other similar short-term studies which have confirmed the adverse effect of PM air pollution. These associations were stronger in asthmatic subjects compared with those in healthy ones. There are significant adverse effects of ambient air PM on pulmonary function of adolescents, especially asthmatics. PMID- 29796886 TI - Endophytic bacterium Buttiauxella sp. SaSR13 improves plant growth and cadmium accumulation of hyperaccumulator Sedum alfredii. AB - Inoculation with endophytic bacterium has been considered as a prospective application to improve the efficiency of phytoextraction. In this study, the effect of Buttiauxella sp. SaSR13 (SaSR13), a novel endophytic bacterium isolated from the root of hyperaccumulator Sedum alfredii, on plant growth and cadmium (Cd) accumulation in S. alfredii was investigated. Laser scanning confocal microscopic (LSCM) images showed that SaSR13 was mainly colonized in the root elongation and mature zones. The inoculation with SaSR13 to Cd-treated plants significantly enhanced plant growth (by 39 and 42% for shoot and root biomass, respectively), chlorophyll contents (by 38%), and Cd concentration in the shoot and root (by 32 and 22%, respectively). SaSR13 stimulated the development of roots (increased root length, surface area, and root tips number) due to an increase in the indole-3-acid (IAA) concentrations and a decrease in the concentrations of superoxide anion (O2.-) in plants grown under Cd stress. Furthermore, inoculation with SaSR13 enhanced the release of root exudates, especially malic acid and oxalic acid, which might have facilitated the uptake of Cd by S. alfredii. It is suggested that inoculation with endophytic bacterium SaSR13 is a promising bioaugmentation method to enhance the Cd phytoextraction efficiency by S. alfredii. PMID- 29796887 TI - Integral use of plants and their residues: the case of cocoyam (Xanthosoma sagittifolium) conversion through biorefineries at small scale. AB - During last decades, there has been a growing interest of decreasing the environmental impact generated by humans. This situation has been approached from different perspectives being the integral use of raw materials as one of the best alternatives. It was estimated that 3.7 * 109 tonnes of agricultural residues are produced annually worldwide. Then, the integral use of feedstocks has been studied through the biorefinery concept. A biorefinery can be a promissory option for processing feedstocks in rural zones aiming to boost the techno-economic and social growth. However, many plants produced at small scale in rural zones without high industrial use contribute with residues usually not studied as raw materials for other processes. Cocoyam (Xanthosoma sagittifolium) is a plant grown extensively in tropical regions. Nigeria, China, and Ghana are the main producers with 1.3, 1.18, and 0.9 million tonnes/year, respectively. In Colombia, there are no technified crops, but it is used where it is grown mainly as animal feed. This plant consists of leaves, stem, and a tuber but the use is generally limited to the leaves, discarding the other parts. These discarded parts have great potential (lignocellulose and starch). This work proposes different processing schemes using the parts of the plant to obtain value-added products, and their techno-economic and environmental assessment. The simulation was performed with Aspen Plus and the economic package was used for the economic assessment. For the environmental assessment, Waste Algorithm Reduction of the U.S. EPA was implemented. The obtained results showed that the integral use of plants under a biorefinery scheme allows obtaining better techno-economic and environmental performance and that small-scale biorefineries can be a promissory option for boosting rural zones. PMID- 29796888 TI - Impacts of meteorological conditions on wintertime PM2.5 pollution in Taiyuan, North China. AB - Taiyuan frequently experiences heavy PM2.5 pollution in winter under unfavorable meteorological conditions. To understand how the meteorological factors influence the pollution in Taiyuan, this study involved a systematic analysis for a continuous period from November 2016 to January 2017, using near-surface meteorological observations, radiosonde soundings, PM2.5 measurements, and three dimension numerical simulation, in combination with backward trajectory calculations. The results show that PM2.5 concentration positively correlates with surface temperature and relative humidity and anti-correlates with near surface wind speed and boundary layer height (BLH). The low BLH is often associated with a strong thermal inversion layer capping over. In addition to the high local emissions, it is found that under certain synoptic conditions, the southwesterly and southerly winds could bring pollutants from Linfen to Taiyuan, leading to a near-surface PM2.5 concentration higher than 200 MUg m-3. Another pollution enhancing issue is due to the semi-closed basin of Taiyuan affecting the planetary boundary layer (PBL): the surrounding mountains favor the formation of a cold air pool in the basin, which inhibits vertical exchanges of heat, flux, and momentum between PBL and the free troposphere, resulting in stagnant conditions and poor air quality in Taiyuan. These findings can be utilized to improve the understanding of PM2.5 pollution in Taiyuan, to enhance the accuracy of forecasting pollution, and to provide scientific support for policy makers to mitigate the pollution. PMID- 29796889 TI - Association analysis between spatiotemporal variation of vegetation greenness and precipitation/temperature in the Yangtze River Basin (China). AB - The variation in vegetation greenness provides good understanding of the sustainable management and monitoring of land surface ecosystems. The present paper discusses the spatial-temporal changes in vegetation and controlling factors in the Yangtze River Basin (YRB) using Global Inventory Modeling and Mapping Studies (GIMMS) Normalized Difference Vegetation Index (NDVI) for the period 2001-2013. Theil-Sen Median trend analysis, Pearson correlation coefficients, and residual analysis have been used, which shows decreasing trend of the annual mean NDVI over the whole YRB. Spatially, the regions with significant decreasing trends were mainly located in parts of central YRB, and pronounced increasing trends were observed in parts of the eastern and western YRB. The mean NDVI during spring and summer seasons increased, while it decreased during autumn and winter seasons. The seasonal mean NDVI shows spatial heterogeneity due to the vegetation types. The correlation analysis shows a positive relation between NDVI and temperature over most of the YRB, whereas NDVI and precipitation show a negative correlation. The residual analysis shows an increase in NDVI in parts of eastern and western YRB and the decrease in NDVI in the small part of Yangtze River Delta (YRD) and the mid-western YRB due to human activities. In general, climate factors were the principal drivers of NDVI variation in YRB in recent years. PMID- 29796890 TI - Effects of flavor enhancers on the survival and behavior of the red imported fire ant, Solenopsis invicta (Hymenoptera: Formicidae). AB - To understand whether flavor enhancers pose potential risks to the environment, it is important to assess its effects on insects. Therefore, the objective of this study was to evaluate the toxicity of flavor enhancers on the survival and behaviors of the red imported fire ant, Solenopsis invicta. In this study, we found that the mortality of S. invicta workers that were fed glutamic acid monosodium salt hydrate, glycine, L-alanine, succinic acid, succinic acid disodium, inosinate 5'-monophosphate disodium salt hydrate, and GMP were significantly higher than the mortality rates of workers fed sucrose. Moreover, glycine and GMP exhibited the strongest toxicities and caused 100% mortality in workers after 84 h. LC50 values were 0.004 g/ml and 0.02 g/ml for GMP and glycine, respectively. Additionally, at sublethal doses, both GMP and glycine solutions decreased foraging and digging behaviors. Our results suggest that flavor enhancers are toxic to insects and also likely to have a negative impact at sublethal concentrations. PMID- 29796891 TI - Alkylphenol and bisphenol A contamination of urban runoff: an evaluation of the emission potentials of various construction materials and automotive supplies. AB - Alkylphenol (AP) and bisphenol A (BPA) contamination of urban runoff has already been established. Potential sources of these contaminants in runoff are endogenous to the urban watershed and are mainly related to traffic and leaching from construction materials. This article summarizes the results of experimental work carried out on a selection of building materials, automotive materials, and consumables, which can be in contact with rain, to assess their potential emission of alkylphenols, alkylphenol ethoxylates, and bisphenol A into runoff. 36 samples of materials, new and used, across 7 major families of building materials (PVC, concrete, polycarbonate, SBS-modified bitumen, drainage materials) and automotive materials (body, tires) were subjected to leaching tests with methanol and then, for a selection of them, with water. Automotive fluids were also directly analyzed. The results demonstrate the ubiquitous presence of APs and BPA in urban materials and their extractable character with water. The compounds with the strongest emission rates were bisphenol A and nonylphenol. The most important BPA emissions into water (10 to 300 ng/g) were measured for polycarbonate, tires, some car bodies, and PVC. Nonylphenol was leached in large quantities (1 to 10 ng/g) from PVC, some concretes, SBS-modified bitumen, and body samples. The tires were the only materials having a strong emission in octylphenol (1 to 10 ng/g). The analysis of automotive fluids confirmed the presence of BPA (0.3 to 5.5 g/L) and nonylphenol (2.3 to 2.9 mg/L) in brake fluids, while APs and BPA were found at trace levels in coolants and windscreen washer. Graphical abstract ?. PMID- 29796893 TI - [Early colectomy in patients with acute exacerbation of ulcerative colitis]. PMID- 29796892 TI - Ternary cross-coupled nanohybrid for high-efficiency 1H-benzo[d]imidazole chemisorption. AB - 1H-Benzo[d]imidazole (BMA) has been considered as an emerging pharmaceutical organic contaminant, leading to the increasing BMA detection in wastewaters and need to be removed from ecosystem. This study investigated a highly synergistic BMA chemisorption using a novel ternary cross-coupled nanohybrid [gamma-APTES] Fe3O4@PAN@rGO. Magnetic nanoparticles (Fe3O4) were in situ core-shell co precipitated with polyacrylonitrile polymer (PAN). Then, the prepared Fe3O4@PAN was decorated on hexagonal arrays of reduced graphene oxide (rGO) inside the framework of gamma-aminopropyltriethoxysilane ([gamma-APTES]). The final nanohybrid [gamma-APTES]-Fe3O4@PAN@rGO produced adjacent inter-fringe distances of 0.2-0.4 nm corresponded well to (111), (220), and (311) parallel sub-lattices with two oblique intersections at 90 degrees right angle and 60 degrees triangle. The BMA adsorption was favorable in neutral pH 7, aroused temperature (50 degrees C), and controlled by endothermic process. The identified maximum adsorption capacity of 221.73 mg g-1 was 30% higher than the reported adsorbents. The adsorption mechanisms include ion exchange, hydrogen bond, dipole-dipole force, pi-conjugation, electrostatic, and hydrophobic interaction. Graphical abstract The synthetic route of novel nanohybrid [gamma-APTES]-Fe3O4@PAN@rGO was investigated. After BMA adsorption, the adsorbent surface was entirely changed, thus an efficiently facile magnetic separation within 8s. [gamma-APTES] Fe3O4@PAN@rGO formed different oblique intersections of 60 degrees and 90 degrees sub-lattices. PMID- 29796895 TI - [Investigations on in-hospital mortality in pancreatic surgery : Results of a multicenter observational study]. AB - BACKGROUND: The rate of hospital mortality (in-hospital mortality) after complex pancreatic resections cannot be used as a decision-making criterion with no further analysis and specification. Such analysis has to provide a risk-adjusted benchmarking including a continuous evaluation taking into account the frequency of a surgical procedure and its competent perioperative management. MATERIAL AND METHODS: As part of the Prospective Evaluation study Elective Pancreatic surgery (PEEP), overall 2003 patients were enrolled over a 3-year time period from 01 January 2006 to 12 December 2008, who underwent elective pancreatic surgery in 27 surgical departments. Included in the study were only hospitals which perform pancreatic resections. In addition to the analysis of the current situation of the operative treatment of pancreatic diseases, the complex aspects of the in hospital mortality as a main outcome parameter were investigated. RESULTS: Out of all enrolled patients (n = 2003), 75 patients (3.7%) died during the hospital stay. In the group of 1045 patients with partial pancreaticoduodenectomy (PD), 43 patients did not survive the hospital stay (4.1%). Similarly, such low in hospital mortality rates were observed after total pancreatoduodenectomy (3.8%) and after left-sided resection of the pancreas (1.9%). With respect to a univariate risk stratification, advanced age and an American Society of Anaesthesiologists (ASA) score of 3 and 4 had a significant impact on in-hospital mortality. Multivariate regression analysis within the PD group revealed an increased need for blood transfusions and a delay in oral feeding as factors closely associated with specific complications with a significant impact on in hospital mortality. Significant differences in the in-hospital mortality rates were found when comparing hospital volume groups, such as 10-20 vs. >20 cases/year for the 831 Kausch-Whipple procedures for adenocarcinoma and chronic pancreatitis. DISCUSSION: An adequate in-hospital mortality rate in the continuous benchmarking represents an acceptable quality level of structural and therapeutic predictions in pancreatic resections. The participation of surgical departments with complex oncosurgical interventions in clinical multicenter observational studies as a contribution to research on surgical care appears reasonable and recommendable since the results of such studies can provide a contribution to decision-making processes in daily surgical practice. PMID- 29796894 TI - [Sacral nerve modulation in coloproctology]. AB - Sacral nerve modulation and stimulation (SNM/SNS) is a minimally invasive treatment for fecal incontinence, which has become widely established in recent years. Modulation of sacral nerve roots occurs through an electrode which is placed in the sacral foramina S2-4. By complex spinal and supraspinal mechanisms, rectal compliance is improved and anal incontinence episodes are reduced. The use of SNM is a suitable therapeutic option for nearly all causes of fecal incontinence refractory to conservative treatment. In the majority of patients, a significant reduction of incontinence episodes or a complete relief of symptoms is achieved. These results are also observed in long-term follow-up. Although the efficacy of SNM in constipation is less well established, it may be considered in patients who fail to respond to conservative measures. The role of further potential indications for SNM/SNS in coloproctological disorders is discussed in the present review. PMID- 29796896 TI - [Current concepts of resilience research]. AB - BACKGROUND: Stress-related mental disorders are the most prevalent and cost intensive disorders of our time. On the other hand, the maintenance of mental health despite stressors, i. e. resilience, is a frequent phenomenon. Research on psychological resilience and its underlying mechanisms offers innovative possibilities for health promotion. It requires a consistent understanding of resilience and adequate methods of operationalization. OBJECTIVES: Modern concepts of the definition, operationalization and assessment of resilience as well as its implications for study designs in resilience research. MATERIAL AND METHODS: Analysis and discussion of current works and expert recommendations for the design of resilience research. RESULTS: Resilience research is undergoing a period of transition. Based on a new understanding of resilience as a dynamic and modifiable process, new approaches for operationalization and assessment were proposed. These include, for example, a transdiagnostic approach and the identification of resilience mechanisms, the consideration of stressor exposure in measuring the construct, and longitudinal cohort studies. CONCLUSIONS: In the upcoming decades, further profitable findings from current prospective longitudinal studies can be expected. One challenge for future resilience research consists in the continuous dissemination and implementation of the approaches described. PMID- 29796897 TI - Improved production of 1-deoxynojirymicin in Escherichia coli through metabolic engineering. AB - Azasugars, such as 1-deoxynojirymicin (1-DNJ), are associated with diverse pharmaceutical applications, such as antidiabetic, anti-obesity, anti-HIV, and antitumor properties. Different azasugars have been isolated from diverse microbial and plant sources though complicated purification steps, or generated by costly chemical synthesis processes. But the biosynthesis of such potent molecules using Escherichia coli as a heterologous host provides a broader opportunity to access these molecules, particularly by utilizing synthetic biological, metabolic engineering, and process optimization approaches. This work used an integrated approach of synthetic biology, enzyme engineering, and pathway optimization for rational metabolic engineering, leading to the improved production of 1-DNJ. The production of 1-DNJ in recombinant E. coli culture broth was confirmed by enzymatic assays and mass spectrometric analysis. Specifically, the pathway engineering for its key precursor, fructose-6-phosphate, along with optimized media condition, results in the highest production levels. When combined, 1-DNJ production was extended to ~ 273 mg/L, which is the highest titer of production of 1-DNJ reported using E. coli. PMID- 29796898 TI - An efficient biocatalytic synthesis of imidazole-4-acetic acid. AB - OBJECTIVE: To develop a new and efficient biocatalytic synthesis method of imidazole-4-acetic acid (IAA) from L-histidine (L-His). RESULTS: L-His was converted to imidazole-4-pyruvic acid (IPA) by an Escherichia coli whole-cell biocatalyst expressing membrane-bound L-amino acid deaminase (mL-AAD) from Proteus vulgaris firstly. The obtained IPA was subsequently decarboxylated to IAA under the action of H2O2. Under optimum conditions, 34.97 mM IAA can be produced from 50 mM L-His, with a yield of 69.9%. CONCLUSIONS: Compared to the traditional chemical synthesis, this biocatalytic method for IAA production is not only environmentally friendly, but also more cost effective, thus being promising for industrial IAA production. PMID- 29796899 TI - Trace analysis of multi-class phytohormones in Oryza sativa using different scan modes in high-resolution Orbitrap mass spectrometry: method validation, concentration levels, and screening in multiple accessions. AB - Phytohormones are signaling and regulating metabolites involved in numerous plant processes, including growth, development, and responses to stress. Currently, the focus is on the analysis of multiple phytohormones in order to characterize crosstalk and hormone signaling networks. In this paper, representative phytohormones of the major classes are simultaneously determined in rice tissues by a generic solid-liquid extraction, followed by liquid chromatography and electrospray ionization high-resolution tandem mass spectrometry using a Q ExactiveTM instrument. After a thorough optimization of the sample preparation, the analytical method was fully validated toward the ultra-trace quantification of six a priori selected plant hormones using three scan modes of the quadrupole Orbitrap instrument: full-scan high-resolution mass spectrometry, targeted single ion monitoring (t-SIM), and t-SIM followed by data-dependent tandem mass spectrometry. Overall, a similar quantitative performance was noticed for the different scan modes. The analytical method was successfully applied to measure basal phytohormone levels in six different rice accessions, comprising Oryza sativa ssp. japonica, indica, and Oryza glaberrima. Hormone concentrations were higher in shoots than in roots or at least similar. Except for a lower level of salicylic acid in shoots of O. glaberrima versus O. sativa, no other differences in hormone levels could be noticed that were dependent of the (sub)species assignment of the analyzed accessions. Making use of the benefits of full-scan high-resolution mass spectrometry, a first post-run suspect screening was performed, suggesting - based on accurate mass measurements and isotopic patterns - the possible presence of about 50 additional plant hormones in the rice tissues. Graphical abstract ?. PMID- 29796902 TI - Negative-ion atmospheric pressure ionisation of semi-volatile fluorinated compounds for ultra-high-performance liquid chromatography tandem mass spectrometry analysis. AB - In this work, the feasibility of negative-ion atmospheric pressure chemical ionisation (APCI) and atmospheric pressure photoionisation (APPI) for ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) determination of fluorotelomer alcohols (FTOHs), fluorinated octanesulfonamides (FOSAs) and fluorinated octanesulfonamido-ethanols (FOSEs) was evaluated. The study of the effect of mobile phase composition on the atmospheric pressure ionisation of these compounds indicated that methanol/water mixtures provided the best responses in APCI, while acetonitrile/water with a post-column addition of toluene as dopant was the most appropriated mixture in APPI. Under the optimal working conditions, most of the target compounds produced the ion [M-H]- as base peak, although in-source collision-induced dissociation fragment ions in APCI and APPI and superoxide adduct ions [M+O2]-* in APPI were also present. These ions proved to be more useful as precursor ions for MS/MS determination than the adduct ions generated in electrospray. Although the UHPLC-APCI-MS/MS method allowed the determination of these semi-volatile compounds at low concentration levels, the analysis by UHPLC-APPI-MS/MS provided the lowest limits of detection and it was applied to the analysis of water samples in combination with solid phase extraction. Quality parameters demonstrated the good performance of the proposed method, providing low method limits of detection (0.3-6 ng L-1), good precision (RSD % < 5%) and an accurate quantification (relative error % < 14%). Among the river water samples analysed by the developed method, 4:2 FTOH and N EtFOSA were determined at 30 and 780 ng L-1, respectively. PMID- 29796900 TI - Monitoring dynamic release of intracellular hydrogen peroxide through a microelectrode based enzymatic biosensor. AB - A high sensitive and selective hydrogen peroxide (H2O2) biosensor was fabricated on the basis of reduced hemoglobin (Hb) and single-walled carbon nanotubes (SWCNTs) for detecting the release of H2O2 from living HepG2 cancer cells in the process of the in situ biosynthesis of ZnO quantum. The modification of carbon fiber microelectrode (CFME) was carried out by physical adsorption. By the scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), the dense cover of surface and successful immobilization were characterized. Electrochemical investigation demonstrates that the as-prepared modified microelectrode showed a quasi-reversible process toward the reduction of H2O2, which exhibited a linear range from 0.51 to 10.6 MUM, with a limit of detection of 0.23 MUM. This microelectrode biosensor was applied for the quantification of the change of H2O2 concentration released from HepG2 cells through the in situ biosynthesis of ZnO quantum dots, which was further confirmed by the fluorescence staining. PMID- 29796901 TI - Rapid detection and differentiation of Staphylococcus colonies using an optical scattering technology. AB - Staphylococcus species are a major pathogen responsible for nosocomial infections and foodborne illnesses. We applied a laser-based BARDOT (bacterial rapid detection using optical scattering technology) for rapid colony screening and detection of Staphylococcus on an agar plate and differentiate these from non Staphylococcus spp. Among the six growth media tested, phenol red mannitol agar (PRMA) was found most suitable for building the Staphylococcus species scatter image libraries. Scatter image library for Staphylococcus species gave a high positive predictive value (PPV 87.5-100%) when tested against known laboratory strains of Staphylococcus spp., while the PPV against non-Staphylococcus spp. was 0-38%. A total of nine naturally contaminated bovine raw milk and ready-to-eat chicken salad samples were tested, and BARDOT detected Staphylococcus including Staphylococcus aureus with 80-100% PPV. Forty-five BARDOT-identified bacterial isolates from naturally contaminated foods were further confirmed by tuf and nuc gene-specific PCR and 16S rRNA gene sequence. This label-free, non-invasive on plate colony screening technology can be adopted by the food industries, biotechnology companies, and public health laboratories for Staphylococcus species detection including S. aureus from various samples for food safety and public health management. Graphical abstract. PMID- 29796903 TI - Hyphal development in Candida albicans from different cell states. AB - Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast, pseudohyphal, and hyphal growth forms (polymorphism) is one of the most investigated virulence attributes of C. albicans. The usual method for inducing hypha formation in the lab is by diluting cells from a saturated culture into fresh medium at 37 degrees C. The molecular mechanism at action under these conditions has been previously investigated. C. albicans can also form hyphae in growing cells without dilution. The ability of C. albicans to form hyphae in different cell states facilitates the fungus to adapt varied host environments during infection. A recent study by Su et al. uncovered the molecular mechanism for how C. albicans develops hyphae under the condition without inoculation. N-Acetylglucosamine (GlcNAc) stimulates filamentation in log phase cells through transcriptional down regulation of NRG1, the major repressor of hyphal development. Instead of cAMP PKA pathway, GlcNAc sensor Ngs1 is responsible for this process. Ngs1 binds to GlcNAc to activate its N-acetyltransferase activity, leading to the induction of BRG1 expression. The increased level of BRG1 could repress NRG1 transcripts, resulting in hyphal growth. Hyphal development in log phase cells induced by serum or neutral pH also requires activation of BRG1 to down-regulate NRG1 transcription. Therefore, hyphal induction under the condition without inoculation is trigged by Brg1-mediated removal of Nrg1 inhibition. This review describes our current understanding of the molecular mechanism underlying hyphal development, the best studied virulence factor in C. albicans. These will expand the number of potential drug targets with novel modes of action for anti virulence therapeutics. PMID- 29796904 TI - Critical roles of Shugoshin and histones as tension sensors during mitosis. AB - Biorientation of paired sister chromosomes is required to maintain mitotic fidelity. A critical signal indicative of bipolar attachment is tension between cohesion-linked sister chromatids. Key components of the tension signaling apparatus include the Shugoshin family of proteins and the tension sensing motif of histone H3. Shugoshin proteins are recruited to chromatin to create discrete domains integral to tension sensing. Many factors involved in the chromatin association of Shugoshin proteins are well established, most strikingly through modifications found directly on centromeric and pericentric chromatin. It has been well established that phosphorylation at the centromere is essential to nucleating Shugoshin recruitment, but recent evidence revealed a role for pericentric histones and acetylation in modulating Shugoshin recruitment and activity. These data demonstrate that chromatins are not simply passive cargo during mitosis, but are instead actively involved in their segregation. PMID- 29796905 TI - [Thyroid gland and the heart : Pathophysiological background, diagnostic and therapeutic consequences]. AB - BACKGROUND: Irregularities in thyroid-specific laboratory parameters are frequent in the general population. Observational studies have shown associations between dysfunction of the thyroid gland and cardiovascular morbidity and mortality. OBJECTIVE: The aim of this review is to give a critical overview of the relationship and treatment recommendations for the simultaneous occurrence of functional disorders of the thyroid gland and the heart. MATERIAL AND METHODS: Literature searches were conducted in PubMed and Medline. RESULTS AND CONCLUSION: Overt and also to a lesser extent subclinical hyperthyroidism are of relevance for cardiovascular mortality and morbidity, even though interventional studies are missing. Therefore, basic thyroid diagnostics are recommended when cardiovascular diseases occur or deteriorate. Whereas overt hyperthyroidism and hypothyroidism are treated immediately, subclinical thyroid dysfunction disorders require confirmation by laboratory testing. In cases with confirmed subclinical hyperthyroidism and heart disease, a thyroid-specific treatment is meaningful (e. g. with radioiodine). At what point a subclinical hypothyroidism should be treated is controversial. We usually initiate substitution treatment with levothyroxine only in patients with a thyroid-stimulating hormone (TSH) level > 10 mIU/l. A control of baseline thyroid parameters is necessary prior to initiation of any treatment with amiodarone or with deterioration of the general condition. PMID- 29796906 TI - Anti-cytokine therapy and plasma DNA in patients with rheumatoid arthritis. AB - BACKGROUND: Extracellular DNA (ecDNA) is increased in inflammation and it also induces inflammation. In patients with rheumatoid arthritis (RA), plasma ecDNA is higher than in healthy controls. Due to low specificity, it cannot be used for screening, but it might be useful for monitoring and prognosis of therapy success. The effect of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) on plasma ecDNA in RA patients with regards to its subcellular origin has not been analyzed yet. The aim of this study was to describe the effects of bDMARDs on plasma ecDNA and its nuclear (nDNA) and mitochondrial (mtDNA) fractions in patients with RA. METHODS: Plasma samples of 32 patients with RA were collected before, as well as 3 and 6 months after starting the treatment with bDMARDs. Total plasma ecDNA was quantified fluorometrically. The subcellular origin of ecDNA was assessed using real time PCR. Treatment success was monitored using DAS28 and C-reactive protein (CRP). RESULTS: The clinical status of patients improved. Both DAS28 and CRP decreased by 52 and 73% after 3 months of treatment. Plasma ecDNA decreased significantly only after 6 months (by 26%). Real-time PCR showed that both, nDNA and mtDNA decreased by 63 and by 45% after 6 months. CONCLUSION: Treatment with bDMARDs decreases plasma ecDNA of both nuclear and mitochondrial origin. Dynamics of ecDNA is slower than dynamics of standard clinical markers. Therefore, it is likely to be not useful for monitoring of the disease progress, at least for RA. PMID- 29796907 TI - The impact of anti-U1-RNP positivity: systemic lupus erythematosus versus mixed connective tissue disease. AB - Anti-U1-RNP positivity remains mandatory for the mixed connective tissue disease (MCTD) diagnosis, reason for which anti-U1-RNP occurrence in patients with lupus clinical features might determine diagnostic issues. Thus, the prevalence of 25 30% for anti-RNP was reported in John Hopkins and LUMINA lupus cohorts and also 13% prevalence for the anti-U1-RNP in Euro-Lupus cohort. Presence of anti-U1-RNP antibodies in patients fulfilling SLE criteria (but not the MCTD ones) was associated with manifestations such as Raynaud phenomenon, musculoskeletal and lung impairment or nail fold capillaroscopy changes, some clinical features frequently encountered in MCTD patients and only rarely described in lupus population. The use of more specific markers such as 70 kDa anti-U1-RNP or anti Sm-D was proposed for discriminating between SLE and MCTD. In addition, the IgM serotype of anti-U1-RNP seems more frequently expressed in SLE, while the IgG serotype alone in MCTD. Better acknowledgement of possible clinical involvements in lupus subsets, such as the peculiarities related to the anti-U1-RNP positivity, could provide access to early diagnosis of rather rare but possible severe lupus organ impairments (e.g. pulmonary arterial hypertension). PMID- 29796908 TI - Endoscopic Necrosectomy Through Percutaneous Self-Expanding Metal Stents May Be a Promising Additive in Treatment of Necrotizing Pancreatitis. AB - BACKGROUND: The recommended treatment of infected walled-off necrosis (WON) in necrotizing pancreatitis entails a step-up treatment approach starting with endoscopic necrosectomy (ETDN). AIMS: To report a small number of cases from 2013 to 2016 that were not amenable to or failed to respond to ETDN, and to describe a new, minimally invasive technique that may be a promising supplement to ETDN in this difficult patient population. METHODS: Using the Seldinger technique, a fully covered self-expanding metal stent (SEMS) was placed percutaneously in order to drain, irrigate, and debride WON. After resolution, the stent was removed. We reviewed electronic patient records and defined clinical success as complete WON resolution with removal of internal as well as percutaneous drains and stents. RESULTS: Five patients underwent treatment with SEMS placement. The mean length of the WON was 33.4 cm. Clinical success was achieved in four patients after an average of 5.75 necrosectomy sessions. One patient died from severe sepsis. Adverse events included severe abdominal pain and productive cutaneous fistulae (two patients). CONCLUSIONS: In our small case series, endoscopic necrosectomy through a percutaneous SEMS seemed beneficial and safe in the treatment of infected WON. PMID- 29796909 TI - Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA. AB - BACKGROUND: Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS: To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS: We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS: There were 52 patients, 67% females, with a mean age of 59 +/- 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS: In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing. PMID- 29796910 TI - Frailty Assessment Predicts Acute Outcomes in Patients Undergoing Screening Colonoscopy. AB - BACKGROUND: Colonoscopy is associated with multiple adverse outcomes. With an aging population undergoing colorectal cancer screening, few modalities exist to assess the patient risk prior to colonoscopy. Frailty, the age-related decline in reserve and function across multiple organ systems, predicts poor surgical outcomes, but its role in endoscopy is unclear. AIMS: This prospective cohort study assesses the efficacy of frailty in predicting acute colonoscopy outcomes. METHODS: Participants aged >= 50 years undergoing screening colonoscopy at a tertiary care center were recruited over 2 months ending in July 2017. Frailty was assessed using a validated 20-s upper-extremity frailty test, which measures the capacity of muscle performance. Demographic data, American Society of Anesthesiologists (ASA) status, and Charlson comorbidity index (CCI) were evaluated. Procedure-related adverse events and cardiopulmonary changes during and in the immediate post-procedure period were recorded. Adverse events were stratified into minor and major events. Chi-square and ANCOVA models were used in the analysis. RESULTS: Ninety-nine adults (mean age 62.8 years) were enrolled, among which 49 were non-frail and 50 were pre-frail/frail; 50 were female. Overall, 55 participants experienced a total of 87 adverse events. Frailty and ASA status were significantly associated with colonoscopy adverse events (p = 0.01 and p = 0.02, respectively). Age and CCI did not predict colonoscopy outcomes. CONCLUSIONS: Compared to age and CCI, frailty status better predicts colonoscopy outcomes in older adults. Among adults undergoing colonoscopy, routine frailty screening should be considered for risk stratification. Additional prospective studies evaluating frailty measurements in endoscopy will further clarify its role in forecasting adverse events. PMID- 29796911 TI - Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors. AB - BACKGROUND: Recently, problems associated with proton pump inhibitor (PPI) use have begun to surface. PPIs influence the gut microbiota; therefore, PPI use may increase the risk of enteric infections and cause bacterial translocation. In this study, we investigated fecal microbiota composition, fecal organic acid concentrations and pH, and gut bacteria in the blood of the same patients before and after PPI use. METHODS: Twenty patients with reflux esophagitis based on endoscopic examination received 8 weeks of treatment with PPIs. To analyze fecal microbiota composition and gut bacteria in blood and organic acid concentrations, 16S and 23S rRNA-targeted quantitative RT-PCR and high-performance liquid chromatography were conducted. RESULTS: Lactobacillus species were significantly increased at both 4 and 8 weeks after PPI treatment compared with bacterial counts before treatment (P = 0.011 and P = 0.002, respectively). Among Lactobacillus spp., counts of the L. gasseri subgroup, L. fermentum, the L. reuteri subgroup, and the L. ruminis subgroup were significantly increased at 4 and 8 weeks after treatment compared with counts before treatment. Streptococcus species were also significantly increased at 4 and 8 weeks after PPI treatment compared with counts before treatment (P < 0.01 and P < 0.001, respectively). There was no significant difference in the total organic acid concentrations before and after PPI treatment. Detection rates of bacteria in blood before and after PPI treatment were 22 and 28%, respectively, with no significant differences. CONCLUSIONS: Our quantitative RT-PCR results showed that gut dysbiosis was caused by PPI use, corroborating previous results obtained by metagenomic analysis. PMID- 29796912 TI - Tumor Necrosis Factor Ligand-Related Molecule 1A Regulates the Occurrence of Colitis-Associated Colorectal Cancer. AB - BACKGROUND: Tumor necrosis factor ligand-related molecule 1 A (TLlA) is closely related to the occurrence and development of inflammatory bowel disease. AIMS: We aimed to explore whether TLlA was involved in the occurrence of colitis associated colorectal cancer (CAC). METHODS: Firstly, azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to construct the CAC mice model in wild type (WT) and TL1A transgenic (Tg) mice with TL1A high expression. The histopathological analysis was used for the evaluation of inflammation level, and the immunohistochemistry staining analysis was used to test the expression and location of proliferating cell nuclear antigen (PCNA) and beta-catenin. Secondly, the HCT116 and HT29 cell lines were used for knockdown of TL1A gene for further assay including cell viability, cell clone, cell apoptosis and matrigel invasion. Western blot were used for quantitative protein expression of beta-catenin and downstream oncogenes including c-myc and Cyclin D1 after knockdown of TL1A gene. RESULTS: The evaluation of inflammation level showed that the disease activity index score and tumor formation rate were significantly higher in AOM + DSS/Tg group than that in AOM + DSS/WT group. The expression of PCNA, beta-catenin, c myc, and Cyclin D1 in AOM + DSS/Tg group was significantly higher than that in AOM + DSS/WT group. The cell experiment showed that TL1A knockdown inhibited the cell proliferation, invasion, and migration. Moreover, the expression of c-myc and Cyclin D1 was significantly decreased after TL1A knockdown. CONCLUSIONS: TL1A can induce tumor cell proliferation and promote the occurrence of CAC by activating Wnt/beta-catenin pathway. PMID- 29796914 TI - Brownout: another threat to ICU physicians and nurses. PMID- 29796916 TI - Is there still a place for the Swan-Ganz catheter? No. PMID- 29796913 TI - Angle of His Accentuation Is a Viable Alternative to Dor Fundoplication as an Adjunct to Laparoscopic Heller Cardiomyotomy: Results of a Randomized Clinical Study. AB - BACKGROUND: There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM. METHODS: A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL. RESULTS: Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups. CONCLUSION: AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time. CLINICAL REGISTRATION NUMBER: CTRI: REF/2014/06/007146. PMID- 29796915 TI - Is there still a place for the Swan-Ganz catheter? Yes. PMID- 29796917 TI - Is there still a place for the Swan-Ganz catheter? We are not sure. PMID- 29796918 TI - Computer-based self-training for CT colonography with and without CAD. AB - OBJECTIVES: To determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning. METHODS: Institutional review board approval and patients' informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres. After an introductory course, readers performed a baseline assessment test (37 cases) using CAD as second reader. Then they were randomized (1:1) to perform either a computer-based self-training (150 cases verified at colonoscopy) with CAD as second reader or the same training without CAD. The same assessment test was repeated after completion of the training programs. Main outcome was per lesion sensitivity (>= 6 mm). A generalized estimating equation model was applied to evaluate readers' performance and the impact of CAD use during training. RESULTS: After training, there was a significant improvement in average per lesion sensitivity in the unassisted phase, from 74% (356/480) to 83% (396/480) (p < 0.001), and in the CAD-assisted phase, from 83% (399/480) to 87% (417/480) (p = 0.021), but not in average per patient sensitivity, from 93% (390/420) to 94% (395/420) (p = 0.41), and specificity, from 81% (260/320) to 86% (276/320) (p = 0.15). No significant effect of CAD use during training was observed on per patient sensitivity and specificity, nor on per lesion sensitivity. CONCLUSIONS: A computer-based self-training program for CTC improves readers' per lesion sensitivity. CAD as second reader does not have a significant impact on learning if used during training. KEY POINTS: * Computer-based self-training for CT colonography improves per lesion sensitivity of novice readers. * Self-training program does not increase per patient specificity of novice readers. * CAD used during training does not have significant impact on learning. PMID- 29796919 TI - CT and MRI of pancreatic cancer: there is no rose without a thorn! PMID- 29796920 TI - Steering Charge Kinetics of Tin Niobate Photocatalysts: Key Roles of Phase Structure and Electronic Structure. AB - Tin niobate photocatalysts with the phase structures of froodite (SnNb2O6) and pyrochlore (Sn2Nb2O7) were obtained by a facile solvothermal method in order to explore the impact of phase structure and electronic structure on the charge kinetics and photocatalytic performance. By employing tin niobate as a model compound, the effects of phase structure over electronic structure, photocatalytic activity toward methyl orange solution and hydrogen evolution were systematically investigated. It is found that the variation of phase structure from SnNb2O6 to Sn2Nb2O7 accompanied with modulation of particle size and band edge potentials that has great consequences on photocatalytic performance. In combination with the electrochemical impedance spectroscopy (EIS), transient photocurrent responses, transient absorption spectroscopy (TAS), and the analysis of the charge-carrier dynamics suggested that variation of electronic structure has great impacts on the charge separation and transfer rate of tin niobate photocatalysts and the subsequent photocatalytic performance. Moreover, the results of the X-ray photoelectron spectroscopy (XPS) indicated that the existent of Sn4+ species in Sn2Nb2O7 could result in a decrease in photocatalytic activity. Photocatalytic test demonstrated that the SnNb2O6 (froodite) catalyst possesses a higher photocatalytic activity toward MO degradation and H2 evolution compared with the sample of Sn2Nb2O7 (pyrochlore). On the basis of spin resonance measurement and trapping experiment, it is expected that photogenerated holes, O2 *, and OH* active species dominate the photodegradation of methyl orange. PMID- 29796921 TI - Fatal Hyperammonemic Encephalopathy in a Pediatric Patient After Roux-en-Y Gastric Bypass. PMID- 29796922 TI - Treatment of Obesity in Young People-a Systematic Review and Meta-analysis. AB - Obesity in the young is increasingly prevalent. Early, effective intervention is paramount. Treatment options are lifestyle modifications, pharmacological therapies, endoscopic treatments and bariatric surgery. However, the relative effectiveness of these treatments in young patients remains unclear. We systematically identify and meta-analyse studies evaluating weight loss treatments in young people (< 21 years) with obesity. From 16,372 identified studies, 83 were eligible for meta-analysis. Bariatric surgery resulted in high short/medium-term weight loss (pooled estimate 14.04 kg/m2). Lifestyle and pharmacological therapies impacted weight more moderately (pooled estimate 0.99 and 0.94 kg/m2 respectively). Due to its high efficacy, bariatric surgery should be considered earlier when treating obesity in young people. However, due to the invasiveness and inherent risks of bariatric surgery, all other weight loss routes should be exhausted first. PMID- 29796923 TI - Adult-born dentate granule cell excitability depends on the interaction of neuron age, ontogenetic age and experience. AB - Early during their maturation, adult-born dentate granule cells (aDGCs) are particularly excitable, but eventually develop the electrophysiologically quiet properties of mature cells. However, the stability versus plasticity of this quiet state across time and experience remains unresolved. By birthdating two populations of aDGCs across different animal ages, we found for 10-month-old rats the expected reduction in excitability across cells aged 4-12 weeks, as determined by Egr1 immunoreactivity. Unexpectedly, cells 35 weeks old (after genesis at an animal age of 2 months) were as excitable as 4-week-old cells, in the dorsal hippocampus. This high level of excitability at maturity was specific for cells born in animals 2 months of age, as cells born later in life did not show this effect. Importantly, excitability states were not fixed once maturity was gained, but were enhanced by enriched environment exposure or LTP induction, indicating that any maturational decrease in excitability can be compensated by experience. These data reveal the importance of the animal's age for aDGC excitability, and emphasize their prolonged capability for plasticity during adulthood. PMID- 29796924 TI - Genetic diversity and identification of putative recombination events in grapevine rupestris stem pitting-associated virus. AB - The impact of recombination on variant classification and the use of different genomic regions to identify virus variants were investigated using a diversity study performed on grapevine rupestris stem pitting-associated virus (GRSPaV). Three surveys were conducted to investigate the genetic diversity of GRSPaV and to compare the ability of the GRSPaV coat protein and replicase domains to classify virus variants. GRSPaV variants identified in the surveys clustered into five of the six currently recognised lineages, and a seventh, previously unclassified lineage was detected. A correlation was observed between the detection of recombinant GRSPaV sequences and inconsistencies in classification when using different genome regions for analysis. PMID- 29796925 TI - Restricted viral cDNA synthesis in cell lines that fail to support productive infection by bovine leukemia virus. AB - Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis, which results in significant economic losses on many affected farms. BLV infects a wide range of animals as well as cell lines derived from various mammalian species and organs; however, studies show that only some cell lines support sustained production of viral progeny. The differences between cells that produce viral progeny and those that do not are unclear. The aim of this study was to identify the steps of BLV replication that are associated with the capacity of a cell to support a productive infection. Eleven cell lines derived from various species were categorized into two groups, those that produce BLV progeny and those that do not, and the efficiency of viral attachment was compared. In addition, viral entry and reverse transcription were compared for two BLV producing cell lines and three non-producing cell lines. BLV attached to and entered all of the tested cells. However, synthesis of viral DNA was inhibited in all three non-virus-producing cell lines, suggesting that BLV production was blocked either prior to or at the stage of reverse transcription. These results increase our understanding of the BLV life cycle and should enable better control over the spread of BLV. PMID- 29796926 TI - Development of a TaqMan MGB RT-PCR assay for the detection of type A and subtype H10 avian influenza viruses. AB - H10 subtype avian influenza viruses have caused several epidemics in poultry and mammals, and specific, rapid and sensitive methods for detection are urgently needed. Herein, TaqMan minor groove binder (MGB) probes and multiplex real-time RT-PCR primers were designed based on gene regions encoding conserved domains of the nucleoprotein and H10 hemagglutinin. The developed multiplex real-time RT-PCR assay displayed high specificity, repeatability, and a detection limit of 10 copies per reaction. This diagnostic method could prove valuable for the rapid detection of H10 subtype AIVs in China. PMID- 29796927 TI - Safety of Polysorbate 80 in the Oncology Setting. AB - Polysorbate 80 is a synthetic nonionic surfactant used as an excipient in drug formulation. Various products formulated with polysorbate 80 are used in the oncology setting for chemotherapy, supportive care, or prevention, including docetaxel, epoetin/darbepoetin, and fosaprepitant. However, polysorbate 80, like some other surfactants, is not an inert compound and has been implicated in a number of systemic and injection- and infusion-site adverse events (ISAEs). The current formulation of intravenous fosaprepitant has been associated with an increased risk of hypersensitivity systemic reactions (HSRs). Factors that have been associated with an increased risk of fosaprepitant-related ISAEs include the site of administration (peripheral vs. central venous), coadministration of anthracycline-based chemotherapy, number of chemotherapy cycles or fosaprepitant doses, and concentration of fosaprepitant administered. Recently, two polysorbate 80-free agents have been approved: intravenous rolapitant, which is a neurokinin 1 (NK-1) receptor antagonist formulated with the synthetic surfactant polyoxyl 15 hydroxystearate, and intravenous HTX-019, which is a novel NK-1 receptor antagonist free of synthetic surfactants. Alternative formulations will obviate the polysorbate 80-associated ISAEs and HSRs and should improve overall management of chemotherapy-induced nausea and vomiting.Funding Heron Therapeutics, Inc. PMID- 29796928 TI - Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp). AB - Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes. PMID- 29796929 TI - Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case-control study. AB - Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography tandem mass spectrometry (LC-MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, L-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia. PMID- 29796930 TI - A fusion antitumor peptide regulates proliferation and apoptosis of endothelial cells. AB - The present research has been carried out to elicit the mechanism of antiangiogenic activity of a fusion peptide P2. Peptide P2 was designed by the connection of a heptapeptide MMP inhibitor to ES-2, a fragment of Endostatin. In a previous study, P2 demonstrated strong antiangiogenic and antitumor effect, and the current work explains the antiangiogenic mechanism of P2 through endothelial cell proliferation and apoptosis. In our study, it was shown that P2 inhibited HUVECs proliferation at a low serum concentration and this effect might be achieved through arresting cell cycle by decreasing the expression level of Cyclin D1. In addition, P2 was found to induce apoptosis of HUVECs. Using Western blot, it was indicated that P2 induced the cleavage of Caspase-3, the hallmark protease of apoptosis. The activation and expression of the upstream regulator Caspase-9 can also be affected by P2 treatment. Furthermore, P2 reduced the protein level of antiangiogenic factors Bcl-xL and Bcl-2. These results revealed that P2 regulates endothelial cell apoptosis through intrinsic apoptotic pathway. PMID- 29796932 TI - Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention study. AB - PURPOSE: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. METHODS: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post intervention. RESULTS: Fifty-five females completed the study. In the high phytate-bread group (n = 31) there was no change in any of the iron status biomarkers after 12 weeks of intervention (p > 0.05). In the low-phytate bread group (n = 24) there were significant decreases in both ferritin (mean = 12%; from 32 +/- 7 to 27 +/- 6 ug/L, geometric mean +/- SEM, p < 0.018) and total body iron (mean = 12%; from 6.9 +/- 1.4 to 5.4 +/- 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention. CONCLUSIONS: In Swedish females of reproductive age, 12 weeks of high-phytate wholegrain bread consumption had no effect on iron status. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age. PMID- 29796933 TI - Is Mental Illness a Risk Factor for Hospital Readmission? AB - People with mental illnesses (MI) receive suboptimal care for medical comorbidities and their high risk for readmission may be addressed by adequate medication management and follow-up care. We examined the association between MI, medication changes, and post-discharge outpatient visits with 30-day readmission in 40,048 Medicare beneficiaries hospitalized for acute myocardial infarction, heart failure or pneumonia. Beneficiaries with MI were more likely to be readmitted than those without MI (14 vs. 11%). Probability of readmission was 13 and 12% when medications were dropped or added, respectively, versus 11% when no change was made. Probability of readmission also increased with outpatient visits. PMID- 29796931 TI - Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review. AB - PURPOSE: The management of oesophageal and gastric cancer can cause significant physical decline, impacting on completion rates and outcomes. This systematic review aimed to (i) determine the impact of chemotherapy, chemoradiotherapy and surgery on physical function; (ii) identify associations between physical function and post-operative outcomes; and (iii) examine the effects of rehabilitation on physical function. METHODS: We included randomised controlled trials (RCT), non-RCTs of interventions and cohort studies that measured physical function by objective means in patients with oesophageal or gastric cancer. EMBASE, PubMed, CINAHL, Cochrane Library, SCOPUS, PEDro and the WHO Trial Registry were searched up to June 2016. Risk of bias assessment was performed using a suite of validated tools. RESULTS: Twenty-five studies involving 1897 participants were included. A meta-analysis was not indicated due to the heterogeneity of the literature. Significant reductions in physical function occur in patients undergoing neoadjuvant treatment and in the first 3 months post resection. Lower pre-operative exercise capacity is associated with an increased risk of post-operative pulmonary complications (PPCs). Evidence to support exercise prehabilitation and rehabilitation in these treatment pathways is currently lacking. CONCLUSIONS: Chemotherapy, chemoradiation and surgery lead to reduced physical function in patients with oesophageal and gastric cancer. High quality evidence is lacking to prove the benefit of interventions that improve physical function through the treatment pathway and in recovery, and well designed studies are required. This review was limited due to the heterogeneity of the literature, high risk of bias in some articles and the lack of high quality research encompassing sufficient time points in the patient journey. IMPLICATIONS FOR CANCER SURVIVORS: Curative treatment for oesophago-gastric cancer can negatively impact on physical function. Rehabilitation programmes have considerable potential to enhance physical function across the oesophago-gastric cancer journey. PMID- 29796934 TI - Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial. AB - Mesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans. Here, we develop a prospective, randomized, controlled, observer-blinded phase II trial to assess the clinical safety, feasibility, and therapeutic mechanisms of allogenic bone marrow-derived MSCs (BM-MSCs) by intrathecal infusion in the treatment of patients with cerebral infarction within the middle cerebral artery and with a National Institutes of Health Stroke Scale (NIHSS) score from 15 to 25. Sample size calculation has determined that a patient population of 118, with ischemic stroke between 30 and 90 days following onset, will be randomly divided into experimental (n = 59) and control (n = 59) groups. Then eligible patients will receive four intrathecal infusions of allogenic BM MSCs (1 * 106 cells/kg body weight) once a week. All patients have detailed functional assessments and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. The primary outcome is the score on the modified Rankin Scale at 90 days after treatment, and the second outcomes include multiple indicators of safety and feasibility. And this trial has been registered as ChiCTR-INR-16008908 (25 July 2016). PMID- 29796935 TI - Correction to: Inactivation of NSF ATPase Leads to Cathepsin B Release After Transient Cerebral Ischemia. AB - The author name "Dr. Jiang Wu" needed to be added as the 3rd author. The author institutional affiliations are correspondingly adjusted. The authors regret these errors.The original article has been corrected. PMID- 29796936 TI - Decreased number and increased volume with mitochondrial enlargement of cerebellar synaptic terminals in a mouse model of chronic demyelination. AB - Impaired nerve conduction, axonal degeneration, and synaptic alterations contribute to neurological disabilities in inflammatory demyelinating diseases. Cerebellar dysfunction is associated with demyelinating disorders, but the alterations of axon terminals in cerebellar gray matter during chronic demyelination are still unclear. We analyzed the morphological and ultrastructural changes of climbing fiber terminals in a mouse model of hereditary chronic demyelination. Three-dimensional ultrastructural analyses using serial block-face scanning electron microscopy and immunostaining for synaptic markers were performed in a demyelination mouse model caused by extra copies of myelin gene (PLP4e). At 1 month old, many myelinated axons were observed in PLP4e and wild-type mice, but demyelinated axons and axons with abnormally thin myelin were prominent in PLP4e mice at 5 months old. The density of climbing fiber terminals was significantly reduced in PLP4e mice at 5 months old. Reconstruction of climbing fiber terminals revealed that PLP4e climbing fibers had increased varicosity volume and enlarged mitochondria in the varicosities at 5-month-old mice. These results suggest that chronic demyelination is associated with alterations and loss of climbing fiber terminals in the cerebellar cortex, and that synaptic changes may contribute to cerebellar phenotypes observed in hereditary demyelinating disorders. PMID- 29796937 TI - Clinical impact of molecular classifications in gastric cancer. AB - Treatment options to gastric cancer (GC) have been changing in recent years from a standard to a tailored approach. Different individualized procedures can range from endoscopic resection, D2 with open or minimally invasive approach, to neo adjuvant therapy followed by extended surgery. In more advanced stages, a combined approach with the inclusion of intraperitoneal chemo-hyperthermia (HIPEC) may represent a new advanced option. The inclusion of histological type according to Lauren classification in the flowchart of treatment could increase both accuracy and effectiveness of such tailored approach. New molecular classifications of GC have been introduced recently and translational clinical studies are ongoing. These classifications are expected to be included in multidisciplinary treatment of GC. In particular, in the group with microsatellite instability a less extended lymphadenectomy may be proposed. Also tailored neo-adjuvant treatment may be proposed according to molecular classifications. The group of patients with epithelial-to-mesenchymal transition shows very high propensity to peritoneal dissemination, as well as N-metastases, and may benefit from prophylactic HIPEC and extended lymphadenectomy when confirmed in prospective trials. PMID- 29796938 TI - The Rab GTPase activating protein Gyp2 contributes to UV stress tolerance in Metarhizium acridum. AB - GTPase activation protein (GAP) for Rab GTPases can accelerate GTP hydrolysis to alter the activity of Rab GTPases. To explore the function of GAP in entomopathogenic fungi, we constructed a deletion mutant of Gyp2 gene, a member of the Gyp (GAP for Ypt/Rab proteins) family in the locust-specific fungal pathogen, Metarhizium acridum. Results showed that the ?MaGyp2 mutant had dramatically decreased tolerance to ultraviolet irradiation compared to wild type strain. Quantitative real-time PCR revealed that UV irradiation repair related genes Uve1 and WC1 were downregulated in ?MaGyp2 mutant. Seven of other ten Gyp family members had significantly increased transcription in ?MaGyp2 mutant compared with wild type, which may partly rescue the deficiency of MaGyp2. PMID- 29796940 TI - Monitoring and assessment of seasonal land cover changes using remote sensing: a 30-year (1987-2016) case study of Hamoun Wetland, Iran. AB - The availability of Landsat data allows improving the monitoring and assessment of large-scale areas with land cover changes in rapid developing regions. Thus, we pretend to show a combined methodology to assess land cover changes (LCCs) in the Hamoun Wetland region (Iran) over a period of 30-year (1987-2016) and to quantify seasonal and decadal landscape and land use variabilities. Using the pixel-based change detection (PBCD) and the post-classification comparison (PCC), four land cover classes were compared among spring, summer, and fall seasons. Our findings showed for the water class a higher correlation between spring and summer (R2 = 0.94) than fall and spring (R2 = 0.58) seasons. Before 2000, ~ 50% of the total area was covered by bare soil and 40% by water. However, after 2000, more than 70% of wetland was transformed into bare soils. The results of the long term monitoring period showed that fall season was the most representative time to show the inter-annual variability of LCCs monitoring and the least affected by seasonal-scale climatic variations. In the Hamoun Wetland region, land cover was highly controlled by changes in surface water, which in turn responded to both climatic and anthropogenic impacts. We were able to divide the water budget monitoring into three different ecological regimes: (1) a period of high water level, which sustained healthy extensive plant life, and approximately 40% of the total surface water was retained until the end of the hydrological year; (2) a period of drought during high evaporation rates was observed, and a mean wetland surface of about 85% was characterized by bare land; and (3) a recovery period in which water levels were overall rising, but they are not maintained from year to year. After a spring flood, in 2006 and 2013, grassland reached the highest extensions, covering till more than 20% of the region, and the dynamics of the ecosystem were affected by the differences in moisture. The Hamoun wetland region served as an important example and demonstration of the feedbacks between land cover and land uses, particularly as pertaining to water resources available to a rapidly expanding population. PMID- 29796942 TI - Yap-Hippo pathway regulates cerebral hypoxia-reoxygenation injury in neuroblastoma N2a cells via inhibiting ROCK1/F-actin/mitochondrial fission pathways. AB - Yes-associated protein (Yap), a regulator of cellular apoptosis, has been demonstrated to be involved in cerebral ischemia-reperfusion (IR) injury through poorly defined mechanisms. The present study aimed to explore the role of Yap in regulating cerebral IR injury in vitro, with a focus on mitochondrial fission and ROCK1/F-actin pathways. Our data demonstrated that Yap was actually downregulated in N2a cells after cerebral hypoxia-reoxygenation (HR) injury, and that lower expression of Yap was closely associated with increased cell death. However, the reintroduction of Yap was able to suppress the HR-mediated N2a cells death via blocking the mitochondria-related apoptotic signal. At the molecular levels, Yap overexpression sustained mitochondrial potential, normalized the mitochondrial respiratory function, reduced ROS overproduction, limited HtrA2/Omi release from mitochondria into the nucleus, and suppressed pro-apoptotic proteins activation. Subsequently, functional studies have further illustrated that HR-mediated mitochondrial apoptosis was highly regulated by mitochondrial fission, whereas Yap overexpression was able to attenuate HR-mediated mitochondrial fission and, thus, promote N2a cell survival in the context of HR injury. At last, we demonstrated that Yap handled mitochondrial fission via closing ROCK1/F-actin signaling pathways. Activation of ROCK1/F-actin pathways abrogated the protective role of Yap overexpression on mitochondrial homeostasis and N2a cell survival in the setting of HR injury. Altogether, our data identified Yap as the endogenous defender to relieve HR-mediated nerve damage via antagonizing ROCK1/F actin/mitochondrial fission pathways. PMID- 29796943 TI - Sensory neuropathic symptoms in idiopathic Parkinson's disease: prevalence and impact on quality of life. AB - BACKGROUND: Neuropathic symptoms are commonly reported in Parkinson's disease (PD), but robust data on the epidemiology of such symptoms are lacking. The present study sought to investigate the prevalence and determinants of peripheral sensory neuropathic symptoms (PSNS) in idiopathic PD (IPD) and ascertain the effects of such symptoms on the patients' quality of life (QoL). METHODS: Patients with IPD and age-matched and gender-matched controls were screened for neuropathic symptoms using the Michigan Neuropathy Screening Instrument. The impact of neuropathic symptoms on QoL was investigated using the 36-Item Short Form Survey. RESULTS: Fifty-two patients and 52 age-matched and gender-matched controls were recruited. PSNS were reported more frequently in patients with IPD than in the control subjects (57.7 versus 28.8%, p = 0.003). No significant relationships were found between PD-related clinical characteristics (i.e. disease severity and duration, duration of exposure to levodopa) and the presence of PSNS. Significant correlations were found between the number of PSNS and physical functioning (Spearman's Rho - 0.351), even after adjusting for age, gender and Hoehn and Yahr score. CONCLUSION: Our results support the notion of a greater prevalence of PSNS in IPD patients as compared to the general population, which, at least in part, may be secondary to large and/or small fibre peripheral neuropathy. This warrants further investigation in larger studies that include detailed neurophysiological assessments. PMID- 29796941 TI - Motor Cortex Stimulation for Deafferentation Pain. AB - PURPOSE OF REVIEW: Since the early 1990s, motor cortex stimulation (MCS) has been a unique treatment modality for patients with drug-resistant deafferentation pain. While underpowered studies and case reports have limited definitive, data driven analysis of MCS in the past, recent research has brought new clarity to the MCS literature and has helped identify appropriate indications for MCS and its long-term efficacy. RECENT FINDINGS: In this review, new research in MCS, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) are analyzed and compared with historical landmark papers. Currently, MCS is effective in providing relief to 40-64% of patients, with decreasing analgesic effect over time addressed by altering stimulation settings. rTMS and tDCS, two historic, non-invasive stimulation techniques, are providing new alternatives for the treatment of deafferentation pain, with rTMS finding utility in identifying MCS responders. Future advances in electrode arrays, neuro-navigation, and high-definition tDCS hold promise in providing pain relief to growing numbers of patients. Deafferentation pain is severe, disabling, and remains a challenge for patients and providers alike. Over the last several years, the MCS literature has been revitalized with studies and meta-analyses demonstrating MCS effectiveness and providing guidance in identifying responders. At the same time, rTMS and tDCS, two time-honored non-invasive stimulation techniques, are finding new utility in managing deafferentation pain and identifying good MCS candidates. As the number of potential therapies grow, the clinician's role is shifting to personalizing treatment to the unique pain of each patient. With new treatment modalities, this form of personalized medicine is more possible than ever before. PMID- 29796939 TI - Seizure detection: do current devices work? And when can they be useful? AB - PURPOSE OF REVIEW: The unpredictability and apparent randomness of epileptic seizures is one of the most vexing aspects of epilepsy. Methods or devices capable of detecting seizures may help prevent injury or even death and significantly improve quality of life. Here, we summarize and evaluate currently available, unimodal, or polymodal detection systems for epileptic seizures, mainly in the ambulatory setting. RECENT FINDINGS: There are two broad categories of detection devices: EEG-based and non-EEG-based systems. Wireless wearable EEG devices are now available both in research and commercial arenas. Neuro stimulation devices are currently evolving and initial experiences of these show potential promise. As for non-EEG devices, different detecting systems show different sensitivity according to the different patient and seizure types. Regardless, when used in combination, these modalities may complement each other to increase positive predictive value. Although some devices with high sensitivity are promising, practical widespread use of such detection systems is still some way away. More research and experience are needed to evaluate the most efficient and integrated systems, to allow for better approaches to detection and prediction of seizures. The concept of closed-loop systems and prompt intervention may substantially improve quality of life for patients and carers. PMID- 29796944 TI - H13 influenza viruses in wild birds have undergone genetic and antigenic diversification in nature. AB - Among 16 haemagglutinin (HA) subtypes of avian influenza viruses (AIVs), H13 AIVs have rarely been isolated in wild waterfowl. H13 AIVs cause asymptomatic infection and are maintained mainly in gull and tern populations; however, the recorded antigenic information relating to the viruses has been limited. In this study, 2 H13 AIVs, A/duck/Hokkaido/W345/2012 (H13N2) and A/duck/Hokkaido/WZ68/2012 (H13N2), isolated from the same area in the same year in our surveillance, were genetically and antigenically analyzed with 10 representative H13 strains including a prototype strain, A/gull/Maryland/704/1977 (H13N6). The HA genes of H13 AIVs were phylogenetically divided into 3 groups (I, II, and III). A/duck/Hokkaido/W345/2012 (H13N2) was genetically classified into Group III. This virus was distinct from a prototype strain, A/gull/Maryland/704/1977 (H13N6), and the virus, A/duck/Hokkaido/WZ68/2012 (H13N2), both belonging to Group I. Antigenic analysis indicated that the viruses of Group I were antigenically closely related to those of Group II, but distinct from those of Group III, including A/duck/Hokkaido/W345/2012 (H13N2). In summary, our study indicates that H13 AIVs have undergone antigenic diversification in nature. PMID- 29796945 TI - Identification of genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy. AB - KEY MESSAGE: Key genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy release were identified using phytochemistry, transcriptomics, and bioinformatic methods. The molecular mechanism of seed morphophysiological dormancy of Epimedium pseudowushanense B.L.Guo. remains largely unknown. The endogenous abscisic acid (ABA) and gibberellin (GA) content of E. pseudowushanense seeds at three developmental stages were quantitatively determined. The results showed the levels of ABA in E. pseudowushanense seeds decreased during seed embryo growth and development, while levels of GA3 increased during seed embryo growth, and levels of GA4 increased during seed dormancy release and seed sprouting. A high-throughput sequencing method was used to determine the E. pseudowushanense seed transcriptome. The transcriptome data were assembled as 178,613 unigenes and the numbers of differentially expressed unigenes between the seed development stages were compared. Computer analysis of reference pathways revealed that 12 candidate genes were likely to be involved in metabolism and signalling of ABA and GAs. The expression patterns of these genes were revealed by real-time quantitative PCR. Phylogenetic relationships among the deduced E. pseudowushanense proteins and their homologous proteins in other plant species were analysed. The results indicated that EpNCED1, EpNCED2, EpCYP707A1, and EpCYP707A2 are likely to be involved in ABA biosynthesis and catabolism. EpSnRK2 is likely implicated in ABA signalling during seed dormancy. EpGA3ox is likely to be involved in GA biosynthesis. EpDELLA1 and EpDELLA2 are likely implicated in GA signalling. This study is the first to provide the E. pseudowushanense seed transcriptome and the key genes involved in metabolism and signalling of ABA and GAs, and it is valuable for studies on the mechanism of seed morphophysiological dormancy. PMID- 29796946 TI - Comparative metabolomic responses to gibberellic acid and 6-benzylaminopurine in Cunila menthoides Benth. (Lamiaceae): a contribution to understand the metabolic pathways. AB - KEY MESSAGE: Gibberellic acid elicited synthesis of many phenols from different classes and enhanced production of sesquiterpenoids, polyterpenoids, steroids and monoterpenoids compared to control and 6-benzylaminopurine. Little is known about the effects of 6-benzylaminopurine (BA) and gibberellic acid (GA3) on the synthesis of secondary metabolites in species of Lamiaceae. In this study, for the first time, the profile of secondary metabolites in plantlets of Cunila menthoides was characterized, using UPLC-ESI-Qq-oaTOF-MS. Ninety metabolites were identified, including polyphenols and terpenes. BA down-regulated most of the identified molecules in relation to GA3 and MS0 (control). The results showed that GA3 elicited synthesis of many phenols from different classes, and seemed to play a major role in the shikimate pathway in relation to BA. GA3 enhanced production of sesquiterpenoids, polyterpenoids, steroids and monoterpenoids compared to MS0 and BA, and also seemed to positively influence the MEP/DOXP and MVA pathways. These data show the most comprehensive metabolomic profile of Cunila menthoides to date, and the effects of BA and GA3 on the synthesis of secondary metabolites, modulating quantitative aspects of metabolism in Lamiaceae. PMID- 29796947 TI - Isolation, characterization, and evaluation of three Citrus sinensis-derived constitutive gene promoters. AB - KEY MESSAGE: Regulatory sequences from the citrus constitutive genes cyclophilin (CsCYP), glyceraldehyde-3-phosphate dehydrogenase C2 (CsGAPC2), and elongation factor 1-alpha (CsEF1) were isolated, fused to the uidA gene, and qualitatively and quantitatively evaluated in transgenic sweet orange plants. The 5' upstream region of a gene (the promoter) is the most important component for the initiation and regulation of gene transcription of both native genes and transgenes in plants. The isolation and characterization of gene regulatory sequences are essential to the development of intragenic or cisgenic genetic manipulation strategies, which imply the use of genetic material from the same species or from closely related species. We describe herein the isolation and evaluation of the promoter sequence from three constitutively expressed citrus genes: cyclophilin (CsCYP), glyceraldehyde-3-phosphate dehydrogenase C2 (CsGAPC2), and elongation factor 1-alpha (CsEF1). The functionality of the promoters was confirmed by a histochemical GUS assay in leaves, stems, and roots of stably transformed citrus plants expressing the promoter-uidA construct. Lower uidA mRNA levels were detected when the transgene was under the control of citrus promoters as compared to the expression under the control of the CaMV35S promoter. The association of the uidA gene with the citrus-derived promoters resulted in mRNA levels of up to 60-41.8% of the value obtained with the construct containing CaMV35S driving the uidA gene. Moreover, a lower inter individual variability in transgene expression was observed amongst the different transgenic lines, where gene constructs containing citrus-derived promoters were used. In silico analysis of the citrus-derived promoter sequences revealed that their activity may be controlled by several putative cis-regulatory elements. These citrus promoters will expand the availability of regulatory sequences for driving gene expression in citrus gene-modification programs. PMID- 29796950 TI - Language use at Italian medical congresses. PMID- 29796949 TI - Influence of pH Adjustment Parameter for Sol-Gel Modification on Structural, Microstructure, and Magnetic Properties of Nanocrystalline Strontium Ferrite. AB - Synthesis of nanocrystalline strontium ferrite (SrFe12O19) via sol-gel is sensitive to its modification parameters. Therefore, in this study, an attempt of regulating the pH as a sol-gel modification parameter during preparation of SrFe12O19 nanoparticles sintered at a low sintering temperature of 900 degrees C has been presented. The relationship of varying pH (pH 0 to 8) on structural, microstructures, and magnetic behaviors of SrFe12O19 nanoparticles were characterized by X-ray diffraction (XRD), field emission scanning microscope (FESEM), and vibrating sample magnetometer (VSM). Varying the pH of precursor exhibited a strong effect on the sintered density, crystal structure and magnetic properties of the SrFe12O19 nanoparticles. As the pH is 0, the SrFe12O19 produced relatively largest density, saturation magnetization, Ms, and coercivity, Hc, at a low sintering temperature of 900 degrees C. The grain size of SrFe12O19 is obtained in the range of 73.6 to 133.3 nm. The porosity of the sample affected the density and the magnetic properties of the SrFe12O19 ferrite. It is suggested that the low-temperature sintered SrFe12O19 at pH 0 displayed Ms of 44.19 emu/g and Hc of 6403.6 Oe, possessing a significant potential for applying in low temperature co-fired ceramic permanent magnet. PMID- 29796948 TI - Overexpression of VaWRKY14 increases drought tolerance in Arabidopsis by modulating the expression of stress-related genes. AB - KEY MESSAGE: Overexpression of VaWRKY14 increases drought tolerance in Arabidopsis by modulating the expression of stress-related genes, including COR15A, COR15B, COR413, KIN2, and RD29A. The WRKY family is one of a largest transcription factors in plants, and it is a key component of multiple stress responses. In this study, the drought- and cold-induced WRKY family gene VaWRKY14 was isolated and characterized. Phylogenetic analysis indicated that VaWRKY14 belongs to the WRKY IIa subfamily, of which several members participate in biotic and abiotic stress responses in plants. Fluorescence observation from Arabidopsis mesophyll protoplasts transformed with the VaWRKY14::eGFP fusion vector suggested that VaWRKY14 was localized in the nucleus. The VaWRKY14 in yeast cells did not display any transcriptional activity. The expression of VaWRKY14 could be induced by exogenous phytohormones, including salicylic acid (SA) and abscisic acid (ABA). Overexpression of VaWRKY14 enhanced the drought tolerance of transgenic Arabidopsis. Compared with wild-type Arabidopsis, the VaWRKY14-OE lines exhibited higher water content and antioxidant enzyme activities in leaves after drought treatment. RNA sequencing analysis revealed that several stress-related genes, including COR15A, COR15B, COR413, KIN2, and RD29A, were upregulated in transgenic plants relative to their expression in wild-type Arabidopsis under normal conditions. Several genes (3 upregulated and 49 down-regulated) modulated by VaWRKY14 were also affected by drought stress in wild-type plants. These data suggest that VaWRKY14 responds to drought and cold stresses and that drought tolerance may be enhanced by regulating the expression of stress-related genes in Arabidopsis. PMID- 29796951 TI - Liver transplantation due to cerebrotendinous xanthomatosis end-stage liver disease. PMID- 29796952 TI - Cardiac diagnostics before oral propranolol therapy in infantile hemangioma: retrospective evaluation of 234 infants. AB - BACKGROUND: The indication and extent of cardiac screening before oral propranolol therapy (OPT) in patients with infantile hemangioma (IH) has been challenged. In this study, we evaluated pre-OPT cardiac diagnostics in a pediatric IH cohort in our department. METHODS: Retrospective chart review of infants <= 12 months old with IH undergoing OPT. The diagnostics prior to OPT, occurrence of complications, and outcome were recorded. RESULTS: A total of 234 patients were evaluated. The mean age at the onset of OPT was 4.2 +/- 0.3 months, the average duration of OPT was 6.1 +/- 0.1 months, and the average follow-up was 12.3 +/- 0.7 months. Echocardiograms and electrocardiograms were performed prior to OPT in all patients. One hundred and three (44.0%) echocardiograms revealed pathological findings, 19 (8.1%) of which were minor (including atrial septal defects, pulmonary stenosis, and patent ductus arteriosus). Pathological findings were observed in 17 (7.3%) of electrocardiograms, only one (0.4%) of which was minor (suspected cardiac arrhythmia, subsequently excluded by long-term electrocardiogram analysis). These findings did not contraindicate OPT and no severe adverse events associated with OPT occurred during the follow-up period. CONCLUSIONS: Routine cardiac screening by electrocardiogram and echocardiogram before OPT is debatable and not routinely indicated in children with IH. Further studies are necessary to draw definite conclusions on the reasonable indication and extent of this diagnostic approach. PMID- 29796954 TI - Spatial and temporal variation of soil organic carbon in the North China Plain. AB - The organic carbon, permeability test, grain size, chemical composition, and mineral composition were analyzed for 147 samples collected from the Luan River catchment, Hebei province, China, to quantitatively characterize the effects of land use, climate change, sedimentary environment, mineral composition, and chemical composition on the spatial and temporal variation of soil organic carbon (SOC). The results indicate that there was higher SOC content and stronger variation in the south plain than in the northern low mountain. The effects of land use, climate change, and sedimentary environment on SOC distribution were greater than the effects of mineral composition and chemical composition. The cropping systems in the Luan River catchment resulted in significant difference in SOC concentration between the south plain and north mountain. The precipitation mainly transmitted its effects through the sedimentary environment to SOC, which caused the stronger temporal variation in SOC from June to October in the south plain. The north mountain did not have significant temporal variation because of the lower hydraulic conductivity of the sedimentary sequence. The spatial variation of SOC was correlated with land use, and their temporal variation was attributed to climate change and sedimentary environment. Apart from land use, the decision maker can also affect the organic carbon mineral and sequence through the sedimentary environment. PMID- 29796953 TI - Effects of meta-tetrahydroxyphenylchlorin photodynamic therapy on isogenic colorectal cancer SW480 and SW620 cells with different metastatic potentials. AB - The aim of this study is to investigate the antitumor effects and possible mechanisms of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (m THPC-PDT) on human primary (SW480) and metastatic (SW620) colon cancer cell lines. SW480 and SW620 cells were incubated with various concentrations of m THPC, followed by photodynamic irradiation. Subcellular localization of m-THPC in cells was observed with confocal laser scanning microscopy (CLSM). Photocytotoxicity of m-THPC in the two cells was investigated by using MTT assay. The flow cytometry was employed to detect the cell apoptosis. The migration and long-term recovery ability were determined by scratch test and colony formation assay respectively. CLSM showed that m-THPC was mainly distributed within the endoplasmic reticulum (ER) and lysosome of SW480 cells and within the lysosome and mitochondria of SW620 cells. m-THPC-PDT induced a dose-dependent and light energy-dependent cytotoxicity in SW480 and SW620 cells. Apoptosis rate was approximately 65 and 25% in SW480 and SW620 respectively when the concentration of m-THPC increased to 11.76 MUM. However, the rate of necrotic cells had no significant changes in two cell lines. The colony formation and migration ability of the two cell lines were decreased with m-THPC-PDT treatment in a dose dependent manner. PDT with m-THPC not only could effectively inhibit cell proliferation and decrease migration ability and colony formation ability, but also could effectively kill SW480 and SW620 cells in a dose-dependent manner in vitro. These results suggest that m-THPC is a promising sensitizer that warrants further development and extensive studies towards clinical use of colorectal cancer. PMID- 29796955 TI - Augmented Reality Based Navigation for Computer Assisted Hip Resurfacing: A Proof of Concept Study. AB - Implantation accuracy has a great impact on the outcomes of hip resurfacing such as recovery of hip function. Computer assisted orthopedic surgery has demonstrated clear advantages for the patients, with improved placement accuracy and fewer outliers, but the intrusiveness, cost, and added complexity have limited its widespread adoption. To provide seamless computer assistance with improved immersion and a more natural surgical workflow, we propose an augmented reality (AR) based navigation system for hip resurfacing. The operative femur is registered by processing depth information from the surgical site with a commercial depth camera. By coupling depth data with robotic assistance, obstacles that may obstruct the femur can be tracked and avoided automatically to reduce the chance of disruption to the surgical workflow. Using the registration result and the pre-operative plan, intra-operative surgical guidance is provided through a commercial AR headset so that the user can perform the operation without additional physical guides. To assess the accuracy of the navigation system, experiments of guide hole drilling were performed on femur phantoms. The position and orientation of the drilled holes were compared with the pre operative plan, and the mean errors were found to be approximately 2 mm and 2 degrees , results which are in line with commercial computer assisted orthopedic systems today. PMID- 29796956 TI - Fractal Dimension of Erythrocyte Membranes: A Highly Useful Precursor for Rapid Morphological Assay. AB - Morphology of erythrocyte membrane has been recognized as an alternative biomarker of several patho-physiological states. Numerous attempts have been made to upgrade the existing method of primitive manual counting, particularly exploring the light scattering properties of erythrocyte. All the techniques are at best semi-empirical and heavily rely on the effectiveness of the statistical correlations. Precisely, this is due to the lack of a non-empirical scale of the so-called "morphological scores". In this article, fractal dimension of erythrocyte membrane has been used to formulate a suitable scoring scale. Subsequently, the rapid experimental output of flow-cytometry has been functionally related to the mean morphological quantifier of the whole cell population via an optimum neural network model (R2 = 0.98). Moreover, the fractal dimension has been further demonstrated to be an important parameter in early detection of an abnormal patho-physiological state, even without any noticeable poikilocytic transformation in micrometric domain. PMID- 29796958 TI - Investigation of 3H, 99Tc, and 90Sr transport in fractured rock and the effects of fracture-filling/coating material at LILW disposal facility. AB - Batch adsorption, batch diffusion, and flow-through column experiments were conducted using groundwater and fractured rock collected in unsaturated zone to increase our understanding of sorption and transport behavior of radionuclides. Increasing Kd values were observed in the sequence 90Sr, 99Tc, and 3H regardless of the geological media tested. For all sorbing radionuclides, Kd values for the fracture-filling/coating material were observed to be higher than those for without fracture-filling/coating material regardless of the groundwater. These higher Kd values are the result of zeolite mineral in filling/coating material of fractured rock. The batch diffusion and flow-through column experiments were also conducted using the same fractured rock sample, and the results of diffusion and column experiments showed similar trend of radionuclide sorption and transport to sorption experiment. In this study, sorption Kd of radionuclide was determined and used to increase our understanding of radionuclide retardation through fracture-filling/coating materials. PMID- 29796957 TI - Fibrin polymerization simulation using a reactive dissipative particle dynamics method. AB - The study on the polymerization of fibrinogen molecules into fibrin monomers and eventually a stable, mechanically robust fibrin clot is a persistent and enduring topic in the field of thrombosis and hemostasis. Despite many research advances in fibrin polymerization, the change in the structure of fibrin clots and its influence on the formation of a fibrous protein network are still poorly understood. In this paper, we develop a new computational method to simulate fibrin clot polymerization using dissipative particle dynamics simulations. With an effective combination of reactive molecular dynamics formularies and many body dissipative particle dynamics principles, we constructed the reactive dissipative particle dynamics (RDPD) model to predict the complex network formation of fibrin clots and branching of the fibrin network. The 340 kDa fibrinogen molecule is converted into a spring-bead coarse-grain system with 11 beads using a topology representing network algorithm, and using RDPD, we simulated polymerization and formation of the fibrin clot. The final polymerized structure of the fibrin clot qualitatively agrees with experimental results from the literature, and to the best of our knowledge this is the first molecular-based study that simulates polymerization and structure of fibrin clots. PMID- 29796959 TI - Dentin bonding and physicochemical properties of adhesives incorporated with epigallocatechin-3-gallate. AB - The aim was to assess dentin adhesion and physicochemical properties of experimental etch-and-rinse and self-etch adhesives doped with epigallocatechin-3 gallate (EGCG), a well-known collagen crosslinker obtained from green tea (Camellia sinensis). Experimental adhesives were prepared without (0 wt%), with 0.1 or 0.5 wt% EGCG addition. Their degree of conversion was surveyed by FTIR, and bar-shaped specimens were tested to obtain flexural strength and modulus initially and after 1-week ethanol storage. Extracted human molars were prepared, bonded, and cut into resin-dentin sticks for microtensile bond strength test, which was conducted after 24 h or 6-month water storage. Statistical analyses were performed with two-way ANOVA and Tukey's test (p < 0.05). Degree of conversion outcomes depicted a significant polymerization reduction by the addition of EGCG in self-etch adhesive in both concentrations. However, only 0.1% reduced the conversion of etch-and-rinse adhesive. Flexural modulus and strength were significantly diminished (p < 0.05) by the addition of both concentrations of EGCG for the two model adhesives. Dentin-bond strength was reduced after aging with the addition of EGCG to self-etch adhesive. Nevertheless, 0.5% EGCG increased the bond strength of etch-and-rinse adhesive after aging, conversely to the significant reduction for EGCG-free control adhesive. In conclusion, EGCG at 0.5% provides optimal improvements on dentin bonding without altering final polymerization of a model etch-and-rinse adhesive. PMID- 29796961 TI - Correction to: Externalizing and Internalizing Symptoms Moderate Longitudinal Patterns of Facial Emotion Recognition in Autism Spectrum Disorder. AB - The original version of this article unfortunately contained a mistake. In the heading "Data Analytic Plan", under "Level 2" the following equations were published incorrectly. PMID- 29796960 TI - Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder. AB - Atypical functional connectivity (FC) and an imbalance of excitation-to inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy (1H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance. PMID- 29796963 TI - Validation of pharmacist-physician collaboration in psychiatry: 'the Eichberger model'. AB - Background Collaboration between physicians and pharmacists can increase medication safety. In the "Eichberger model" a clinical pharmacist is employed and working full time in a psychiatric hospital. Objective The aim of this study was to determine the expected type of expertise from a clinical pharmacist in psychiatry and the acceptance of the pharmacist's recommendations. Method All email requests to the clinical pharmacist from January 1st to April 30th 2015 were screened retrospectively and type of requester and content of request were extracted. Maintenance rate of drug therapy was analyzed by reviewing patient charts 2 weeks after medication prescription. Results A total of 147 requests were included. 85 (57.8%) requests were from attending physicians and 62 (42.2%) from residents. 82.1% of all physicians were contacting the clinical pharmacist during the study period. Most common reasons for requests were: appropriate drug selection (31.3%), drug interactions (25.2%), possible adverse drug events (17%) and switching drugs (12.2%). The acceptance rate by the physicians was 100%, with an implementation and maintenance rate of both 98.6%. Conclusion We found a high acceptance level of the pharmacist's recommendations. The pharmacist's skills were requested by the majority of physicians and included a in a large variety of specific questions. A pharmacist can play an important role to optimize patient care in collaboration with the physician in psychiatry. PMID- 29796964 TI - Social Disconnection as a Risk Factor for Health among Cambodian Refugees and Their Offspring in the United States. AB - Studies of relatively recently resettled refugees have noted social disconnection, linked to various physical and mental health outcomes, as a concern. Limited studies have examined whether social disconnection and its effects persists within refugee populations resettled more than 3 decades prior. The relationship between social disconnection and self-reported health was explored in a secondary analysis of a cross-sectional needs assessment survey with a snowball sample of 100 Cambodian refugees residing in Connecticut. Social disconnectedness and comorbid health conditions were prevalent. Lack of religious and community engagement were associated with poor health outcomes, while individuals with a lack of ethnic engagement reported better overall health. This study underscores the importance of understanding the specific risks that social disconnection poses to refugees who have resettled many years before and their offspring that may assist in better serving currently settling refugees within the United States. PMID- 29796962 TI - Community pharmacists' views of using a screening tool to structure medicines use reviews for older people: findings from qualitative interviews. AB - Background The Medicines use review (MUR) service, provided by community pharmacists, seeks to optimise patients' use of medicines. There is limited evidence on the clinical effectiveness of this service. Structuring MURs to include an assessment of prescribing appropriateness, facilitated by a validated prescribing screening tool, has the capacity to enhance this service. Objective To explore community pharmacists' views on the facilitators and barriers towards the utilisation of a screening tool as a guide to conducting structured MURs. Setting Community Pharmacy, Northern Ireland. Method Using the 14 domain Theoretical Domains Framework (TDF), semi-structured interviews were conducted with community pharmacists. Interviews were digitally recorded, transcribed verbatim and analysed using the Framework method. Main Outcome Measure Pharmacists' views towards utilisation of a screening tool as a guide to conducting structured MURs. Results Based on the analysis of 15 interviews, 11 TDF domains ('Knowledge', 'Skills', 'Social and professional role and identity', 'Beliefs about capabilities', 'Beliefs about consequences', 'Reinforcement', 'Goals', 'Memory, attention and decision process', 'Environmental context and resources', 'Social influences', 'Behavioural regulation') were deemed relevant. Facilitators included: knowledge of patients, clinical knowledge, perceived professional role, patients' clinical outcomes, influence of peers. Barriers included: prioritisation of other clinical activities, inability to access patients' clinical information, perceived alienation from the primary healthcare team and staffing issues. Conclusions Using the TDF, key facilitators and barriers were identified in the use of a screening tool as a guide to conducting MURs. These findings may assist in further development of MURs as a means to optimise patients' medicines use. PMID- 29796966 TI - Repeated neonaticide: differences and similarities to single neonaticide events. AB - This study aims to identify differences between single and repeat perpetrators of filicide by using register-based data. The study used register-based, comprehensive, nationwide data from both Austria and Finland. The current study covers 23 perpetrators, 20 single and 3 repeat perpetrators, with a total of 28 victims. All victims had a maximum age of 24 h and all perpetrators were women. Every third victim of neonaticide was a victim of a repeat case. The repeat perpetrators were older; had a higher number of children over their lifespan, some of whom lived with them; were more likely to live within established family structures; had higher levels of education and employment; had a higher proportion of personality disorders; and were more likely to identify stress factors during pregnancy. One unexpected finding was low levels of awareness about pregnancy within the perpetrator's circle remain a risk factor, especially for repeat perpetrators. Arguably, the quality of interpersonal relationships these women have may be affected by their own mental health issues and life experience and vice versa. PMID- 29796967 TI - Pre- and postnatal exposure to intimate partner violence among South African HIV infected mothers and infant developmental functioning at 12 months of age. AB - In rural South Africa, pregnant HIV-infected women report high rates of psychological (55%) and physical (20%) intimate partner violence (IPV). IPV increases the risk of infant developmental delays. Such delays may have negative socioemotional and cognitive outcomes throughout the lifespan. This paper assesses the relationship between IPV and infant development in rural South Africa. The present investigation was a cross-sectional add-on follow-up designed retrospectively. A randomly selected sub-sample of mothers from the main randomized controlled trial (n = 72) were asked to participate with their infants at 12 months of age; all women invited agreed to participate. Women were 18.35 +/ 5.47 weeks pregnant; demographics, HIV disclosure status, and pre- and postnatal IPV measured via the Conflict Tactics Scale during pregnancy at baseline and 12 months post-partum were assessed. Infant HIV serostatus and developmental functioning at 12 months of age were assessed. Women were a mean age of 29 +/- 2 years. One third had completed at least 12 years of education and had a monthly income of ~ US$76. At 12 months post-partum, 6% of infants tested HIV seropositive. Postnatal physical IPV was associated with delays in cognitive and receptive language development p < 0.05, but only in unadjusted analyses. This study identified an association between early IPV exposure and infant cognitive and receptive communication delays. Given the small sample size, findings support replication. Longitudinal studies are needed to confirm temporal order and identify appropriate timing for interventions in HIV-exposed infants. PMID- 29796968 TI - Recommendations for the use of ECT in pregnancy: literature review and proposed clinical protocol. AB - Psychiatric disorders are common in pregnancy, affecting 15-29% of pregnant women. Untreated depression has negative health consequences for mother and fetus. Electroconvulsive therapy (ECT) is an effective option for the treatment of severe depression, high suicide risk, catatonia, medication-resistant illness, psychotic agitation, severe physical decline, and other life-threatening conditions. To our knowledge, however, there is no literature that consolidates all the evidence on maternal and fetal risks associated with untreated depression, medications, and ECT then translating it into one cohesive protocol that could serve as a management guide and a source of reassurance to health-care providers involved in such practice. Hoping to facilitate ECT access to perinatal patients, the authors combined their multidisciplinary clinical experience (in perinatal psychiatry, neuropsychiatry and neuromodulation, and anesthesiology) at three different centers in the USA (Brigham and Women's Hospital/Harvard Medical School, The University of Chicago, and Brown University) with a careful and critical literature review and propose guidelines for the administration of ECT in pregnancy. A comprehensive review of the relevant literature regarding both ECT and psychotropic medications in pregnancy was performed, including meta analyses of randomized controlled trials published in general medicine, anesthesiology, psychiatry, and obstetrics journals and guidelines. The indication and appropriateness of ECT in pregnancy must be carefully weighed against the risks of untreated maternal illness and those of alternative treatment options. The safety of ECT in pregnancy has been documented over the last 50 years. The adverse effects in pregnancy are similar to the risks of ECT in any individual. The most common risk to the mother is premature contractions and preterm labor, which occur infrequently and are not clearly caused by ECT. The rates of miscarriages were not significantly different from that of the general population. There have been no associations of ECT with congenital anomalies, either morphologic or behavioral, and no neurocognitive disturbances in the child. ECT is a reasonably safe and effective treatment alternative for management of many psychiatric disorders in pregnant patients. The authors provide recommendations for treatment modifications in pregnancy-based physiologic changes that occur during that period and consolidate them into a protocol that can assist clinicians in improving access and safety of ECT for pregnant patients. PMID- 29796969 TI - Wilfrid Rall. PMID- 29796965 TI - Challenges Facing a Rural Opioid Epidemic: Treatment and Prevention of HIV and Hepatitis C. AB - PURPOSE OF REVIEW: This article reviews recent epidemiologic trends in HIV and hepatitis C virus (HCV) and strategies for treatment and prevention of these infections as they relate to the opioid epidemic. RECENT FINDINGS: Among people who inject drugs (PWID) in the United States (US), HIV diagnoses are decreasing, while HCV is increasing. Care for HIV and HCV relies heavily on specialist infrastructure, which is lacking in rural areas. Antiretrovirals for HIV and direct-acting antivirals for HCV are effective among PWID, yet multiple barriers make it difficult for rural injectors to access these treatments. Similarly, access to syringe service programs, medication-assisted therapy for opioid addiction, and pre-exposure prophylaxis for HIV are all limited in rural areas. Previous research on HIV and HCV among PWID has focused on urban or international populations, yet the US opioid epidemic is moving away from metropolitan centers. Increasing rurality of opioid injection brings unique challenges in treatment and prevention. Research into the care of HIV, HCV, and opioid use disorder among rural populations is urgently needed. PMID- 29796970 TI - Stabilizing displayed proteins on vegetative Bacillus subtilis cells. AB - Microbes engineered to display heterologous proteins could be useful biotechnological tools for protein engineering, lignocellulose degradation, biocatalysis, bioremediation, and biosensing. Bacillus subtilis is a promising host to display proteins, as this model Gram-positive bacterium is genetically tractable and already used industrially to produce enzymes. To gain insight into the factors that affect displayed protein stability and copy number, we systematically compared the ability of different protease-deficient B. subtilis strains (WB800, BRB07, BRB08, and BRB14) to display a Cel8A-LysM reporter protein in which the Clostridium thermocellum Cel8A endoglucanase is fused to LysM cell wall binding modules. Whole-cell cellulase measurements and fractionation experiments demonstrate that genetically eliminating extracytoplasmic bacterial proteases improves Cel8A-LysM display levels. However, upon entering stationary phase, for all protease-deficient strains, the amount of displayed reporter dramatically decreases, presumably as a result of cellular autolysis. This problem can be partially overcome by adding chemical protease inhibitors, which significantly increase protein display levels. We conclude that strain BRB08 is well suited for stably displaying our reporter protein, as genetic removal of its extracellular and cell wall-associated proteases leads to the highest levels of surface-accumulated Cel8A-LysM without causing secretion stress or impairing growth. A two-step procedure is presented that enables the construction of enzyme coated vegetative B. subtilis cells that retain stable cell-associated enzyme activity for nearly 3 days. The results of this work could aid the development of whole-cell display systems that have useful biotechnological applications. PMID- 29796971 TI - Structural and enzymatic characterization of acetolactate decarboxylase from Bacillus subtilis. AB - Acetoin is an important physiological metabolite excreted by microbes. Its functions include avoiding acidification, participating in regulation of the NAD+/NADH ratio, and storing carbon. Acetolactate decarboxylase is a well characterized anabolic enzyme involved with 3-hydroxy butanone (acetoin). It catalyzes conversion of the (R)- and (S)-enantiomers of acetolactate to generate the single product, (R)-acetoin. In addition to the X-ray crystal structure of acetolactate decarboxylase from Bacillus brevis, although the enzyme is widely present in microorganisms, very few atomic structures of acetolactate decarboxylase are reported. In this paper, we solved and reported a 1.5 A resolution crystal structure of acetolactate decarboxylase from Bacillus subtilis. Dimeric assembly is observed in the solved structure, which is consistent with the elution profile conducted by molecular filtration. A zinc ion is coordinated by highly conserved histidines (191, 193, and 204) and conserved glutamates (62 and 251). We performed kinetic studies on acetolactate decarboxylase from Bacillus subtilis using circular dichroism, allowing the conversion of acetolactate to chiral acetoin for real-time tracking, yielding a Km value of 21 mM and a kcat value of 2.2 s-1. Using the two enantiomers of acetolactate as substrates, we further investigated the substrate preference of acetolactate decarboxylase from Bacillus subtilis by means of molecular docking and dynamic simulation in silico. The binding free energy of (S)-acetolactate was found to be ~ 30 kcal/mol greater than that of (R)-acetolactate, indicating a more stable binding for (S)-acetolactate. PMID- 29796972 TI - Three-Dimensional Surface Point Cloud Ultrasound for Better Understanding and Transmission of Ultrasound Scan Information. AB - Ultrasound is notoriously plagued by high user dependence. There is a steep drop off in information in going from what the sonographer sees during image acquisition and what the interpreting radiologist is able to view at the reading station. One countermeasure is probe localization and tracking. Current implementations are too difficult and expensive to use and/or do not provide adequate detail and perspective. The aim of this work was to demonstrate that a protocol combining surface three-dimensional photographic imaging with traditional ultrasound images may be a solution to the problem of probe localization, this approach being termed surface point cloud ultrasound (SPC-US). Ultrasound images were obtained of major vessels in an ultrasound training phantom, while simultaneously obtaining surface point cloud (SPC) 3D photographic images, with additional scanning performed on the right forearm soft tissues, kidneys, chest, and pelvis. The resulting sets of grayscale/color Doppler ultrasound and SPC images are juxtaposed and displayed for interpretation in a manner analogous to current text-based annotation or computer-generated stick figure probe position illustrations. Clearly demonstrated is that SPC-US better communicates information of probe position and orientation. Overall, it is shown that SPC-US provides much richer image representations of probe position on the patients than the current prevailing schemes. SPC-US turns out to be a rather general technique with many anticipated future applications, though only a few sample applications are illustrated in the present work. PMID- 29796974 TI - Cardiovascular disease in the literature: A selection of recent original research papers. PMID- 29796973 TI - The presence and expression of the HIF-1alpha in the respiratory intestine of the bronze Corydoras Corydoras aeneus (Callichthyidae Teleostei). AB - Bronze corydoras (Corydoras aeneus) is a small diurnal activity fish from South America. Under hypoxia conditions, it uses the posterior part of the intestine as an accessory respiratory organ. The present PCR studies demonstrated higher expression of HIF-1alpha (hypoxia-inducible factor) gene in the respiratory than that in digestive part of bronze corydoras intestine. Further, immunolocalization studies using antibodies specific to HIF-1alpha and transmission electron microscopy (TEM) revealed the presence of HIF-1alpha epitopes in the intestine of Corydoras aeneus. In the respiratory intestine, the numerous clusters of gold particles visualizing HIF-1alpha antibody were observed within fibroblasts, whereas in the digestive tract of this species, single gold grains in the epithelial cells were noted. On the other hand, the presence of HIF-1alpha and the cytoplasmic domain of the epidermal growth factor receptor (EGFR) in the respiratory intestine of bronze corydoras assumes their interactions in the system where these factors appeared for the first time. The non-obligatory air breathing fishes using their digestive tract as an accessory respiratory organ during hypoxia conditions are very interesting for the studies of the processes that control HIF-1alpha expression and squamous cell proliferation. PMID- 29796975 TI - Differences in attenuation pattern in myocardial SPECT between CZT and conventional gamma cameras. AB - BACKGROUND: In myocardial perfusion imaging (MPI), single-photon emission tomography (SPECT) soft-tissue attenuation by the abdomen, breasts, and lateral chest wall may create artifacts that mimic true perfusion defects. This may cause misdiagnosis of myocardial perfusion. The aim of the present study was to compare the localization, extent, and depth of attenuation artifacts in MPI SPECT for a multi-pinhole cadmium zinc telluride (CZT) camera vs a conventional gamma camera. METHODS: Phantom and patient measurements were performed using a CZT camera (GE NM 530c) and a conventional gamma camera (GE Ventri). All images were attenuation corrected with externally acquired low-dose computed tomography. The localization, extent, and depth of the attenuation artifact were quantified by comparing attenuation-corrected and non-attenuation-corrected images. RESULTS: Attenuation artifacts were shifted from the inferolateral wall to the lateral wall using the CZT camera compared to a conventional camera in both the patient and the phantom. The extent of the attenuation artifact was significantly larger for the CZT camera compared to the conventional camera (23 +/- 5% vs 15 +/- 5%, P < .001) for patients and the result was similar for the phantom (28% vs 19%). Furthermore, the depth of the attenuation artifact (percent of maximum counts) was less pronounced for the CZT camera than for the conventional camera, both for phantom measurements (73% vs 67%) and patients (72 +/- 3% vs 68 +/- 4%, P < .001). CONCLUSIONS: Attenuation artifacts are found in different locations to different extents and depths when using a CZT camera vs a conventional gamma camera for MPI SPECT. This should be taken into consideration when evaluating MPI SPECT studies to avoid misinterpretation of myocardial perfusion distribution. PMID- 29796976 TI - Characterizing the literature on validity and assessment in medical education: a bibliometric study. AB - INTRODUCTION: Assessment in Medical Education fills many roles and is under constant scrutiny. Assessments must be of good quality, and supported by validity evidence. Given the high-stakes consequences of assessment, and the many audiences within medical education (e. g., training level, specialty-specific), we set out to document the breadth, scope, and characteristics of the literature reporting on validation of assessments within medical education. METHOD: Searches in Medline (Ovid), Web of Science, ERIC, EMBASE (Ovid), and PsycINFO (Ovid) identified articles reporting on assessment of learners in medical education published since 1999. Included articles were coded for geographic origin, journal, journal category, targeted assessment, and authors. A map of collaborations between prolific authors was generated. RESULTS: A total of 2,863 articles were included. The majority of articles were from the United States, with Canada producing the most articles per medical school. Most articles were published in journals with medical categorizations (73.1% of articles), but Medical Education was the most represented journal (7.4% of articles). Articles reported on a variety of assessment tools and approaches, and 89 prolific authors were identified, with a total of 228 collaborative links. DISCUSSION: Literature reporting on validation of assessments in medical education is heterogeneous. Literature is produced by a broad array of authors and collaborative networks, reported to a broad audience, and is primarily generated in North American and European contexts. Our findings speak to the heterogeneity of the medical education literature on assessment validation, and suggest that this heterogeneity may stem, at least in part, from differences in constructs measured, assessment purposes, or conceptualizations of validity. PMID- 29796978 TI - Correction to: Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010. AB - An error was subsequently identified in the article, and the following correction should be noted. PMID- 29796977 TI - Prescription of Zolpidem and the Risk of Fatal Motor Vehicle Collisions: A Population-Based, Case-Crossover Study from South Korea. AB - BACKGROUND: Zolpidem is one of the most frequently used hypnotics worldwide, but associations with serious adverse effects such as motor vehicle collisions have been reported. OBJECTIVE: The objective of this study was to evaluate the association of fatal motor vehicle collisions with a prescription for zolpidem, considering the context of the motor vehicle collisions. METHODS: We conducted a case-crossover study, where each case served as its own control, by linking data about fatal motor vehicle collisions from the Korean Road Traffic Authority between 2010 and 2014 with national health insurance data. The case period was defined as 1 day before the fatal motor vehicle collisions, and was matched to four control periods at 90-day intervals. Conditional logistic regression was performed to calculate the odds ratio for fatal motor vehicle collisions associated with zolpidem exposure, and odds ratios were adjusted for time-varying exposure to confounding medications. A stratified analysis was performed by age group (younger than 65 years or not), the Charlson Comorbidity Index, and whether patients were new zolpidem users. RESULTS: Among the 714 subjects, the adjusted odds ratio for a fatal motor vehicle collision associated with a prescription for zolpidem the previous day was 1.48 (95% confidence interval 1.06-2.07). After stratification, a significantly increased risk was observed in subjects with a high Charlson Comorbidity Index (odds ratio 1.81; 95% confidence interval 1.16 2.84), the younger age group (odds ratio: 1.62; 95% confidence interval 1.03 2.56), and new zolpidem users (odds ratio 2.37; 95% confidence interval 1.40 4.00). CONCLUSION: A prescription for zolpidem on the previous day was significantly related to an increased risk of fatal motor vehicle collisions in this population-based case-crossover study. PMID- 29796979 TI - Semiparametric temporal process regression of survival-out-of-hospital. AB - The recurrent/terminal event data structure has undergone considerable methodological development in the last 10-15 years. An example of the data structure that has arisen with increasing frequency involves the recurrent event being hospitalization and the terminal event being death. We consider the response Survival-Out-of-Hospital, defined as a temporal process (indicator function) taking the value 1 when the subject is currently alive and not hospitalized, and 0 otherwise. Survival-Out-of-Hospital is a useful alternative strategy for the analysis of hospitalization/survival in the chronic disease setting, with the response variate representing a refinement to survival time through the incorporation of an objective quality-of-life component. The semiparametric model we consider assumes multiplicative covariate effects and leaves unspecified the baseline probability of being alive-and-out-of-hospital. Using zero-mean estimating equations, the proposed regression parameter estimator can be computed without estimating the unspecified baseline probability process, although baseline probabilities can subsequently be estimated for any time point within the support of the censoring distribution. We demonstrate that the regression parameter estimator is asymptotically normal, and that the baseline probability function estimator converges to a Gaussian process. Simulation studies are performed to show that our estimating procedures have satisfactory finite sample performances. The proposed methods are applied to the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international end-stage renal disease study. PMID- 29796980 TI - Predicting Return to Work in a Heterogeneous Sample of Recently Injured Workers Using the Brief OMPSQ-SF. AB - Purpose (1) to examine the ability of the Orebro Musculoskeletal Pain Screening Questionnaire-short version (OMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification. Methods Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5-15 days of their injury. Eligible participants (N = 213 in total) were administered the OMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the OMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the OMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2-7 weeks. Results The total OMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total OMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing OMPSQ-SF total score to return to PID within 2-7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79). Conclusion The results provide strong support for the use of the OMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type. PMID- 29796981 TI - Development and Implementation of a Mental Health Work Rehabilitation Program: Results of a Developmental Evaluation. AB - Purpose Long-term work disability due to common mental disorders (CMDs) is a growing problem. Yet optimal interventions remain unclear and little is known about implementation challenges in everyday practice. This study aimed to support and evaluate, in real time, the development and implementation of a work rehabilitation program (WRP) designed to promote post-CMD return-to-work (RTW). Methods A 2-year developmental evaluation was performed using a participatory approach. At program outset, the researchers held five work meetings to revise the program's logic model and discuss its underlying change theory with clinicians. Data collection tools used throughout the study period were structured charts of activities conducted with workers (n = 41); in-depth interviews with program clinicians and managers (n = 9); and participant observation during work meetings. Quantitative data were analyzed using descriptive statistics. Qualitative data underwent thematic analysis using a processual approach. Results Three types of activity were developed and implemented: individual and group interventions targeting workers, and joint activities targeting partners (physicians, employers, others). While worker targeted activities were generally implemented as planned, joint activities were sporadic. Analysis of the implementation process revealed five challenges faced by clinicians. Determinants included clinicians, host organization, sociopolitical context and resources provided by the evaluation. Conclusion The program studied is original in that it is based on the best available scientific knowledge, yet adapted to contextual particularities. The identified implementation challenges highlight the need for greater importance to be placed on the external, non-program context to ensure sustainable implementation in everyday practice. PMID- 29796982 TI - Workplace-Based Rehabilitation of Upper Limb Conditions: A Systematic Review. AB - Purpose The objective of this systematic review was to identify, collate and analyse the current available evidence on the effectiveness of workplace-based rehabilitative interventions in workers with upper limb conditions on work performance, pain, absenteeism, productivity and other outcomes. Methods We searched Medline, Cochrane Library, Scopus, Web of Science, Academic Search Premier, Africa-Wide Information, CINAHL, OTSeeker and PEDro with search terms in four broad areas: upper limb, intervention, workplace and clinical trial (no date limits). Studies including neck pain only or musculoskeletal pain in other areas were not included. Results Initial search located 1071 articles, of which 80 were full text reviewed. Twenty-eight articles were included, reporting on various outcomes relating to a total of seventeen studies. Nine studies were of high methodological quality, seven of medium quality, and one of low quality. Studies were sorted into intervention categories: Ergonomic controls (n = 3), ergonomic training and workstation adjustments (n = 4), exercise and resistance training (n = 6), clinic-based versus workplace-based work hardening (n = 1), nurse case manager training (n = 1), physiotherapy versus Feldenkrais (n = 1), and ambulant myofeedback training (n = 1). The largest body of evidence supported workplace exercise programs, with positive effects for ergonomic training and workstation adjustments, and mixed effects for ergonomic controls. Ambulant myofeedback training had no effect. The remaining three categories had positive effects in the single study on each intervention. Conclusion While there is substantial evidence for workplace exercise programs, other workplace-based interventions require further high quality research. Systematic review registration PROSPERO CRD42017059708. PMID- 29796983 TI - Effects of Restoring the Primary Dentition with Stainless-Steel Crowns on Children's Salivary Nickel and Chromium Levels, and the Associations with Saliva pH: a Preliminary Before-After Clinical Trial. AB - Nickel and chromium existing in stainless-steel crowns (SSCs, used in pediatric dentistry) might be cytotoxic and allergenic. However, no in vivo studies have examined their salivary levels in children using SSCs, or in young children without SSCs. Also, the effect of acidity on metal ion release has not yet been evaluated in any previous in vivo studies in the whole literature. Therefore, this preliminary before-after clinical trial was conducted. Salivary nickel/chromium levels of 30 children before and after 2 months of placement of SSCs were measured using atomic absorption spectrophotometry. Salivary pH was measured with a digital pH meter. The effects of treatment, pH, number of SSCs, gender, and age on salivary ions were analyzed statistically (alpha = 0.05, beta = 0.15). Salivary nickel concentrations increased from 4.9010 +/- 4.7390 to 5.6320 +/- 4.7210 MUg/L (P = 0.000, paired t test). Chromium increased from 0.3273 +/- 0.5214 to 0.4199 +/- 0.6404 MUg/L (P = 0.016). Saliva pH increased from 6.81 +/- 0.52 to 7.04 +/- 0.47 (P = 0.000). Ion levels were not correlated with pH (P > 0.14), except chromium in the follow-up (rho = - 0.435, P = 0.016). Nickel increase (but not chromium increase) was correlated with pH increase (rho = 0.367, P = 0.046). Age was only correlated with baseline chromium (rho = 0.373, P = 0.042). Being male was associated with baseline/follow-up nickel levels (P <= 0.030). SSC number was not correlated with ions or pH (P > 0.36). It was shown for the first time that SSCs might increase salivary nickel and chromium concentrations and reduce saliva acidity. Nickel increase might be in line with pH elevation. The raised pH might be associated with reduced chromium release. Boys might have higher nickel levels than might girls, with or without SSCs. PMID- 29796985 TI - ? PMID- 29796984 TI - Subsequent infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in patients with prior infection or fecal colonization. AB - In clinical practice, there is a growing need to assess the impact of prior colonization or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (EPE) on new EPE infections. We have investigated the frequency of, and duration to, a subsequent EPE infection in patients with prior fecal carriage or infection with EPE. Culture data for 3272 EPE-positive patients in Western Sweden during 2004-2014 were evaluated. The median follow-up time was 3.7 years. The first recorded EPE-positive fecal screen, or clinical (urine, blood) culture, and subsequent EPE-positive clinical samples were analyzed, focusing on the first and last recurrence of EPE infection. ESBL Escherichia coli dominated (95%). Almost all (94%) patients initially positive in fecal screen (n = 1436) and 72 and 71% of those initially positive in urine (n = 1717) and blood (n = 119) had no further EPE clinical isolates. Subsequent EPE bacteremia was only detected in 0.7, 1.6, and 4.2% of the respective patient group. Recurrent EPE-positive urine cultures occurred in 27% (460/1717), most (75%) within 6 months, and rarely (13%) after 1 year. Repeated EPE-positive clinical samples were significantly (p < 0.01) more common in patients > 65 years and in men with ESBL Klebsiella pneumoniae. In our low-endemic setting, subsequent EPE infections in previously colonized patients were rare. On the other hand, in patients previously EPE-positive in urine or blood, subsequent EPE urinary tract infections were common, especially within 6 months and in patients > 65 years old. PMID- 29796986 TI - Against Inflationary Views of Ethics Expertise. AB - Abram Brummett and Christopher Ostertag offer critiques of my argument that clinical ethics consultants have expertise but are not "ethics experts" (Brummett and Ostertag 2018). My argument begins within our less-than-ideal world and asks what a justification of a clinical ethics consultation recommendation might look like under those conditions. It is a challenge to what could be called an "inflationary" position on ethics expertise that requires agreement on or rational proof of metaethical facts about the values at stake in clinical ethics consultation. Brummett and Ostertag critique three distinct steps in the argument. Two of those I have a brief answer for, and an assessment of the third demonstrates that Brummett and Ostertag do not consider the premise upon which I based my account. Instead, they assert a counter-premise without argument, which at best results in a stalemate between our two accounts. However, the reasons supporting my premise still seem to me to be stronger, so I am in the end unconvinced by their critiques. PMID- 29796988 TI - The Fragile X Protein and Genome Function. AB - The fragile X syndrome (FXS) arises from loss of expression or function of the FMR1 gene and is one of the most common monogenic forms of intellectual disability and autism. During the past two decades of FXS research, the fragile X mental retardation protein (FMRP) has been primarily characterized as a cytoplasmic RNA binding protein that facilitates transport of select RNA substrates through neural projections and regulation of translation within synaptic compartments, with the protein products of such mRNAs then modulating cognitive functions. However, the presence of a small fraction of FMRP in the nucleus has long been recognized. Accordingly, recent studies have uncovered several mechanisms or pathways by which FMRP influences nuclear gene expression and genome function. Some of these pathways appear to be independent of the classical role for FMRP as a regulator of translation and point to novel functions, including the possibility that FMRP directly participates in the DNA damage response and in the maintenance of genome stability. In this review, we highlight these advances and discuss how these new findings could contribute to our understanding of FMRP in brain development and function, the neural pathology of fragile X syndrome, and perhaps impact of future therapeutic considerations. PMID- 29796987 TI - High Ki-67 index in fine needle aspiration cytology of follicular thyroid tumors is associated with increased risk of carcinoma. AB - PURPOSE: Preoperative distinction of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is a diagnostic challenge. Our aim was to investigate whether the Ki-67 proliferation index in fine needle aspiration material can contribute to the diagnosis of FTC. METHODS: We analyzed retrospectively cytological Ki-67 index determined in routine clinical setting and clinical data for 61 patients with FTC, 158 patients with FTA and 15 patients with follicular tumor of uncertain malignant potential (FT-UMP) surgically treated and diagnosed by histopathology at Karolinska University Hospital 2006 2017 (Cohort A). A previously published cohort of 109 patients with follicular tumors was re-analyzed as well (Cohort B). RESULTS: In Cohort A, patients with FTC had a higher Ki-67 index (p < 0.001), larger tumor size (p < 0.001) and higher age at diagnosis (p = 0.036) compared to patients with FTA or FT-UMP. Hurthle cell differentiation, present in 50 FTA, 20 FTC and 8 FT-UMP, was associated with higher Ki-67 index (p = 0.009). Multivariate analysis of Cohort A identified a high Ki-67 index (odds ratio [OR]: 1.215, p < 0.001) and large tumor size (OR: 1.038, p < 0.001) as independent predictors of FTC. Results remained consistent after exclusion of Hurthle cell tumors and in pooled analysis of Cohort A + B. The area under curve of the Ki-67 index for predicting FTC was 0.722 and a cut-off for Ki-67 index at above 5% resulted in a specificity at 93% and sensitivity at 31%. Subgroup analysis of FTCs in Cohort A showed an association of higher Ki-67 index to extrathyroidal extension (p = 0.001) as well as widely invasive subtype (p = 0.019) based on the WHO 2017 classification. CONCLUSIONS: Pre-operative Ki-67 index may add diagnostic information for a subset of patients with follicular thyroid tumors. PMID- 29796989 TI - Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and beta-Amyloid Peptide Load in Hypothyroid Rats. AB - Hypothyroidism is a condition that becomes more prevalent with age. Patients with untreated hypothyroidism have consistently reported symptoms of severe cognitive impairments. In patients suffering hypothyroidism, thyroid hormone supplementation offers the prospect to alleviate the cognitive consequences of hypothyroidism; however, the therapeutic value of TH supplementation remains at present uncertain and the link between cellular modifications associated with hypothyroidism and neurodegeneration remains to be elucidated. In the present study, we therefore evaluated the molecular and behavioral consequences of T3 hormone replacement in an animal model of hypothyroidism. We have previously reported that the antithyroid molecule propylthiouracil (PTU) given in the drinking water favors cerebral atrophy, brain neuroinflammation, Abeta production, Tau hyperphosphorylation, and altered plasticity-related cell signaling pathways in the hippocampus in association with hippocampal-dependent spatial memory deficits. In the present study, our aim was to explore, in this model, the effect of hippocampal T3 signaling normalization on various molecular mechanisms involved in learning and memory that goes awry under conditions of hypothyroidism and to evaluate its potential for recovery of hippocampal dependent memory deficits. We report that T3 supplementation can alleviate hippocampal-dependent memory impairments displayed by hypothyroid rats and normalize key markers of thyroid status in the hippocampus, of neuroinflammation, Abeta production, and of cell-signaling pathways known to be involved in synaptic plasticity and memory function. Together, these findings suggest that normalization of hippocampal T3 signaling is sufficient to reverse molecular and cognitive dysfunctions associated with hypothyroidism. PMID- 29796990 TI - Neuroprotective Effects of Dehydroepiandrosterone Sulfate Through Inhibiting Expression of Matrix Metalloproteinase-9 from Bradykinin-Challenged Astroglia. AB - Dehydroepiandrosterone sulfate (DHEAS), one of the most important neuroactive steroids, is produced in the adrenals and the brain. DHEAS is believed to play a critical role in modulating different forms of cellular control, including processes associated with human neural systems. Its production rate and level in serum, adrenals, and brain gradually decrease with advancing age. The decline of DHEAS level was associated with age-related neuronal dysfunction and degeneration, most probably because the steroids protect the central nervous system (CNS) neurons against neurotoxic challenges. Moreover, increasing studies show that matrix metalloproteinases (MMPs), MMP-9 especially, are upregulated by proinflammatory mediators in the CNS disorders. The increased MMP-9 as an inflammatory biomarker of several CNS disorders that may participate in the CNS inflammation and neurodegeneration. Herein, we investigate the effects of DHEAS on brain inflammation by the model we have defined of bradykinin (BK)-induced MMP 9 expression in rat brain astrocyte (RBA) and its mechanism. The results showed that DHEAS significantly reduce MMP-9 induced by BK. Pretreatment with DHEAS can inhibit BK-stimulated phosphorylation of c-Src and PYK2. Moreover, DHEAS attenuated BK-stimulated NADPH oxidase (Nox)-derived reactive oxygen species (ROS) production, suggesting that DHEAS has an antioxidative effect. We further demonstrated that DHEAS blocked activation of ERK1/2, Akt, and c-Fos/AP-1 by BK. Finally, DHEAS decreased MMP-9-related events including RBA migration and neuronal apoptosis. The results will provide new insights into the anti inflammatory action of DHEAS, supporting that DHEAS may have a neuroprotective effect in the improvement of the CNS disorders by reducing neuroinflammation. PMID- 29796991 TI - Stem Cells from Human Exfoliated Deciduous Teeth Modulate Early Astrocyte Response after Spinal Cord Contusion. AB - The transplantation of stem cells from human exfoliated deciduous teeth (SHED) has been studied as a possible treatment strategy for spinal cord injuries (SCIs) due to its potential for promoting tissue protection and functional recovery. The aim of the present study was to investigate the effects of the early transplantation of SHED on glial scar formation and astrocytic reaction after an experimental model of SCI. Wistar rats were spinalized using the NYU Impactor. Animals were randomly distributed into three groups: control (naive) (animal with no manipulation); SCI (receiving laminectomy followed by SCI and treated with vehicle), and SHED (SCI rat treated with intraspinal SHED transplantation, 1 h after SCI). In vitro investigation demonstrated that SHED were able to express mesenchymal stem cells, vimentin and S100B markers, related with neural progenitor and glial cells, respectively. The acute SHED transplantation promoted functional recovery, measured as from the first week after spinal cord contusion by Basso, Beattie, and Bresnahan scale. Twenty-four and 48 h after lesion, flow cytometry revealed a spinal cord vimentin+ cells increment in the SHED group. The increase of vimentin+ cells was confirmed by immunofluorescence. Moreover, the bioavailability of astrocytic proteins such as S100B and Kir4.1 shown to be increased in the spinal cord of SHED group, whereas there was a glial scar reduction, as indicated by ELISA and Western blot techniques. The presented results support that SHED act as a neuroprotector agent after transplantation, probably through paracrine signaling to reduce glial scar formation, inducing tissue plasticity and functional recovery. PMID- 29796992 TI - Brain Glucose-Sensing Mechanism and Energy Homeostasis. AB - The metabolic and energy state of the organism depends largely on the availability of substrates, such as glucose for ATP production, necessary for maintaining physiological functions. Deregulation in glucose levels leads to the appearance of pathological signs that result in failures in the cardiovascular system and various diseases, such as diabetes, obesity, nephropathy, and neuropathy. Particularly, the brain relies on glucose as fuel for the normal development of neuronal activity. Regions adjacent to the cerebral ventricles, such as the hypothalamus and brainstem, exercise central control in energy homeostasis. These centers house nuclei of neurons whose excitatory activity is sensitive to changes in glucose levels. Determining the different detection mechanisms, the phenotype of neurosecretion, and neural connections involving glucose-sensitive neurons is essential to understanding the response to hypoglycemia through modulation of food intake, thermogenesis, and activation of sympathetic and parasympathetic branches, inducing glucagon and epinephrine secretion and other hypothalamic-pituitary axis-dependent counterregulatory hormones, such as glucocorticoids and growth hormone. The aim of this review focuses on integrating the current understanding of various glucose-sensing mechanisms described in the brain, thereby establishing a relationship between neuroanatomy and control of physiological processes involved in both metabolic and energy balance. This will advance the understanding of increasingly prevalent diseases in the modern world, especially diabetes, and emphasize patterns that regulate and stimulate intake, thermogenesis, and the overall synergistic effect of the neuroendocrine system. PMID- 29796993 TI - SB3 (Ontruzant(r)): A Trastuzumab Biosimilar. AB - SB3 (Ontruzant(r)) is the first biosimilar of the reference anti-HER2 antibody trastuzumab to be approved in the EU. It is approved for use in all indications for which reference trastuzumab is approved, namely HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer. SB3 has similar physicochemical and pharmacodynamic properties to those of reference trastuzumab, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers and women with HER2-positive early or locally advanced breast cancer. SB3 demonstrated clinical efficacy considered equivalent to that of reference trastuzumab in women with HER2-positive early or locally advanced breast cancer. The tolerability, immunogenicity and safety profiles of SB3 were similar to those of reference trastuzumab. The role of reference trastuzumab in the management of HER2-positive cancers is well established and SB3 provides an effective biosimilar alternative for patients requiring trastuzumab therapy. PMID- 29796994 TI - Incidence and survival of primary central nervous system lymphoma (PCNSL): results from the Girona cancer registry (1994-2013). PMID- 29796995 TI - Spanish National Oncological Research Center (CNIO): a bibliometric portrait. AB - INTRODUCTION: Madrid's CNIO (Spanish National Oncological Research Center) ranks among the three first institutions in the world, specifically dedicated to cancer research. CNIO research mainly focuses on three aspects: use of stem cells to fix problematic cancer damage, searches for genes that cause cancer disease, and use of drug design to manage oncological disorders. OBJECTIVES: The main goal of this study is to determine the effectiveness of the 'translation' of basic discoveries generated at this cancer research center, into new interventions aimed at preventing and treating various types of cancer, with bibliometric criteria. METHODS: A corpus of published articles and citations received by CNIO between 1998 and 2016 has been retrieved from the Web of Science (WoS) database. Bibliometric indicators considered here are: citation practices, use of journals on the basis of their impact factors, scientific literature citing CNIO publications, and international connectedness of CNIO researchers. RESULTS: A total of 3510 articles were published by CNIO between 1998 and 2016, 23% of which in journals with impact factors between 10 and 15 and above 15. Along the same period, the institution received 135,769 citations published in more than 5800 journals, where the most important citing journals were the Plos One with 3.6% of all the citing articles, Oncotarget with 1.8%, and Scientific Reports with 1.2%. The highest number of citations was 18,005 in 2007; in terms of average citation rate, the first ranked CNIO research program was in the area of experimental therapeutics (77.79%), followed by molecular oncology (68.1%). This position was provided by the active growth in citation to the articles whose themes are related to the problems of the consequences of the design of preclinical drug candidates and the study of oncological disorders. CONCLUSIONS: From this study on a number of bibliometric characteristics of the Spanish National Oncological Research Center (CNIO), we conclude that the publication activity (since 2006 its scientific production has increased in about 83%), the number of high-quality journals used per year, the high influence, and impact of the journals and organizations citing the institution, consolidate its image as a top-notch oncological research center. PMID- 29796996 TI - Management of patients with implanted cardiac devices during radiotherapy: results of a Spanish survey in radiation oncology departments. AB - BACKGROUND: There is an increasing number of patients with cardiac implantable electronic devices (CIED), either pacemakers or defibrillators, who are receiving a course of radiotherapy. Several guidelines have been published by national societies, but no Spanish national guidelines for management of these patients have been published. More importantly, national clinical practice regarding these patients is not standardised. MATERIALS AND METHODS: Members of the Spanish Breast Cancer Radiation Oncology Group (GEORM in Spanish) were surveyed through an online questionnaire on behalf of the Spanish radiation oncology departments. RESULTS: Only 39.3% of the Spanish radiation oncology departments have policies aimed at CIED carrier patients. Regardless of that, 96.4% of those who responded to the survey refer these patients to their Cardiology department before the start of the course of radiotherapy, and 17.8% of respondents said to manipulate the CIED without any cardiology department direction. A wide range of responses was obtained related to concepts such as "distance from the irradiation field to the CIED" or "safe accumulated doses". CONCLUSIONS: Our results demonstrate the need for national guidelines for CIED patients and the need to promote educational activities addressed to standardise clinical management of these patients in the radiation oncology departments. PMID- 29796997 TI - Does NEMO/IKKgamma protein have a role in determining prognostic significance in uveal melanoma? AB - PURPOSE: Uveal melanoma, although a rare form of cancer, is the most common primary malignancy of the eye in adults. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that transactivates genes involved in the regulation of cell growth, apoptosis, angiogenesis, and metastasis, but the molecular mechanisms that negatively regulate NF-kappaB activation are not fully understood. NF-kappaB can also be activated by DNA damage pathway through NEMO protein. Therefore, the objective of this study is to elucidate the role of NEMO/IKKgamma protein in uveal melanoma patients. METHODS: Seventy-five formalin-fixed paraffin-embedded prospective tissues of uveal melanoma were included in the present study. These cases were reviewed and investigated for the expression of NEMO/IKKgamma protein by immunohistochemistry and validated by western blotting along with the qRT-PCR for mRNA expression. Expression levels were correlated with the clinicopathological parameters and patients' outcome. RESULTS: Immunohistochemistry showed cytoplasmic expression of NEMO/IKKgamma expression in only 22 out of 75 (29.33%) cases. This result was confirmed by western blotting, and correlated well with the immunohistochemical expression of NEMO/IKKgamma protein (48 kDa). In addition, downregulation of this gene was found in 87.93% of the cases when compared with the normal tissues. On statistical analysis, loss of NEMO/IKKgamma protein was correlated with neovascularization, high mitotic count, and presence of vascular loop (p < 0.05). There was less overall survival rate with low expression of NEMO/IKKgamma protein in patients with uveal melanoma. CONCLUSION: This was the first study suggesting the relevant role of NEMO/IKKgamma protein, and highlights the prognostic significance with outcome in uveal melanoma patients. This protein might be used as a screening biomarker in these patients after large-scale validation and translational studies. PMID- 29796998 TI - Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer. AB - PURPOSE: The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence. METHODS: MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion. RESULTS: C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (alpha-SMA, HI-1alpha, MMP11, VEGF, CXCL12, TGF beta1, TGF-betaRII, IL6, TNFalpha) was significantly higher in T-MSCs than in C MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs. CONCLUSIONS: MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment. PMID- 29796999 TI - This is a call to oncologists for action. AB - Cancer cases are growing in an exponential way, likewise the prices of new cancer drugs. Continuing in this way, in the near future, it will be impossible to provide optimum care for all cancer patients. Therefore, it is important to establish mechanisms that enable the National Health Systems to provide the best options of treatment, either through the elaboration of decision-binding frameworks or through other initiatives that guarantee the best quality care for all oncology patients to overcome, in the best possible way, this difficult illness. Here, we review current proposals that have been established by different cancer organizations worldwide, their similarities, their differences and whether they are helpful in a real clinical setting. Facing present reality and despite these organizations' huge efforts, these proposals are not being implemented at all and it does not seem feasible that they will in the short run. In the same way, we support and argue why oncologists should have a crucial and a preponderant role to establish the best way of guaranteeing an equal access to the latest oncology care. PMID- 29797000 TI - Sachem: a chemical cartridge for high-performance substructure search. AB - BACKGROUND: Structure search is one of the valuable capabilities of small molecule databases. Fingerprint-based screening methods are usually employed to enhance the search performance by reducing the number of calls to the verification procedure. In substructure search, fingerprints are designed to capture important structural aspects of the molecule to aid the decision about whether the molecule contains a given substructure. Currently available cartridges typically provide acceptable search performance for processing user queries, but do not scale satisfactorily with dataset size. RESULTS: We present Sachem, a new open-source chemical cartridge that implements two substructure search methods: The first is a performance-oriented reimplementation of substructure indexing based on the OrChem fingerprint, and the second is a novel method that employs newly designed fingerprints stored in inverted indices. We assessed the performance of both methods on small, medium, and large datasets containing 1, 10, and 94 million compounds, respectively. Comparison of Sachem with other freely available cartridges revealed improvements in overall performance, scaling potential and screen-out efficiency. CONCLUSIONS: The Sachem cartridge allows efficient substructure searches in databases of all sizes. The sublinear performance scaling of the second method and the ability to efficiently query large amounts of pre-extracted information may together open the door to new applications for substructure searches. PMID- 29797001 TI - Optimal monochromatic color combinations for fusion imaging of FDG-PET and diffusion-weighted MR images. AB - OBJECTIVE: To investigate the optimal monochromatic color combination for fusion imaging of FDG-PET and diffusion-weighted MR images (DW) regarding lesion conspicuity of each image. METHODS: Six linear monochromatic color-maps of red, blue, green, cyan, magenta, and yellow were assigned to each of the FDG-PET and DW images. Total perceptual color differences of the lesions were calculated based on the lightness and chromaticity measured with the photometer. Visual lesion conspicuity was also compared among the PET-only, DW-only and PET-DW double positive portions with mean conspicuity scores. Statistical analysis was performed with a one-way analysis of variance and Spearman's rank correlation coefficient. RESULTS: Among all the 12 possible monochromatic color-map combinations, the 3 combinations of red/cyan, magenta/green, and red/green produced the highest conspicuity scores. Total color differences between PET positive and double-positive portions correlated with conspicuity scores (rho = 0.2933, p < 0.005). Lightness differences showed a significant negative correlation with conspicuity scores between the PET-only and DWI-only positive portions. Chromaticity differences showed a marginally significant correlation with conspicuity scores between DWI-positive and double-positive portions. CONCLUSIONS: Monochromatic color combinations can facilitate the visual evaluation of FDG-uptake and diffusivity as well as registration accuracy on the FDG-PET/DW fusion images, when red- and green-colored elements are assigned to FDG-PET and DW images, respectively. PMID- 29797002 TI - Prediction of tumor differentiation using sequential PET/CT and MRI in patients with breast cancer. AB - OBJECTIVE: The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUVmax) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion weighted imaging (DWI)-MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. RESULTS: Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 +/- 0.19 vs.1.12 +/- 0.32, p = 0.007). With respect to SUVmax1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUVmax1 (7.92 +/ 4.5 vs.6.19 +/- 3.05, p = 0.099), MTV2.5 (7.90 +/- 9.32 vs.4.38 +/- 5.10, p = 0.095), and TLG2.5 (40.83 +/- 59.17 vs.19.66 +/- 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566-0.782) for assessing high-grade malignancy. CONCLUSIONS: Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET MRI functional parameters. PMID- 29797003 TI - Radiation exposure after 177Lu-DOTATATE and 177Lu-PSMA-617 therapy. AB - PURPOSE: As radionuclide therapy is gaining importance in palliative treatment of patients suffering from neuroendocrine tumour (NET) as well as castration resistant prostate cancer (CRPC), the radiation protection of patients, staff, family members and the general public is of increasing interest. Here, we determine patient discharge dates according to European guidelines. METHODS: In 40 patients with NET and 25 patients with CRPC organ and tumour doses based on the MIRD concept were calculated from data obtained during the first therapy cycle. Planar whole body images were recorded at 0.5, 4, 20, 68 und 92 h postinjection. Residence times were calculated from the respective time-activity curves based on the conjugated view method. Residence times for critical organs were fitted into the commercially available OLINDA software to calculate the organ doses. The doses of tumours and salivary glands were calculated via their self-irradiation by approximation with spheres of equivalent volume. Kidney volumes were gained by organ segmentation, volumes of all other organs were estimated by means of OLINDA and hence were lean body mass corrected. Out of the whole body curves reference points for patient discharge were estimated. RESULTS: In patients with NET discharge dates could be properly estimated from dosimetric data, which is not only crucial for radiation protection, but also makes therapy planning easier. For 177Lu-PSMA-617 ligand therapy it is difficult to seriously estimate a generalized discharge date due to large interpatient variation resulting from different tumor loads and heavy pre-treatment. CONCLUSION: Patient release is predictable for 177Lu-DOTATATE therapy but not for 177Lu-PSMA ligand therapy. PMID- 29797004 TI - Assessing the Impact of Growth Hormone Deficiency (GHD) in Adults: Interpreting Change of the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD). AB - BACKGROUND: This study's purpose was to assess the minimal important difference (MID) for the Treatment-Related Impact Measure-Adult Growth Hormone Deficiency (TRIM-AGHD), a patient-reported outcome measure assessing growth hormone deficiency (GHD) impacts. The measure was demonstrated to have adequate psychometric measurement properties, and be reliable and valid. For scores to be interpretable, the TRIM-AGHD must be responsive to treatment benefit and the MID in scores quantified. METHODS: A prospective, non-interventional, observational, clinic-based survey study of naive-to-treatment adult GHD patients (N = 98) was conducted. Key assessments were at baseline and follow-up (between 4 and approximately 8 weeks), with weekly telephone monitoring post-baseline (last n = 34 patients). Responsiveness was evaluated using the effect size of change scores from baseline to follow-up. MID estimates were derived from distribution-based (half standard deviation [0.5 SD], standard error of measurement [SEm]) and anchor-based methods (patient global rating of change [PGRC]) using change scores from baseline to initial report of minimal improvement in GHD severity. Findings from each method were converged to establish an acceptable MID. RESULTS: Patients were mean age 49.7 years, 65.6% female, and 76.0% Caucasian. The TRIM-AGHD was highly responsive to treatment with the total score effect size being 1.38. For the total score, the 0.5 SD was 8.09 and the SEm was 2.66. The difference found using the PGRC was 20.43. The converged MID value for the total score was 10 points. CONCLUSIONS: The TRIM-AGHD is a highly responsive measure assessing AGHD treatment impacts. A 10-point change score is considered a clinically meaningful improvement. PMID- 29797005 TI - Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to GDF5 Polymorphism. AB - Developmental dysplasia of the hip (DDH) is quite common among Saudi Arabian babies. With an objective to assess the presence of SNP rs143383 and the alleles in the GDF5 gene among patients with DDH, parents, and unaffected siblings, we undertook this case-controlled study. We collected and analyzed for a functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the GDF5 gene (rs143383), 473 blood samples, (100 patients, 200 parents, 73 siblings and 100 healthy controls. We determined the association between the patients' genotype and their fathers', mothers' and siblings' genotype through Chi-square analysis. The majority of those screened possessed the TC genotype, and 61.8% of patients and their fathers had the TT genotype. There was no association between patients' and fathers' genotype, P value < 0.332, 95% CI (0.328-0.346), and between patients' and mothers', P < 0.006, 95% CI (0.004-0.007). When considering DDH patients' and the control group's genotypes, the odds ratios of TT versus other combined (0.641 > 1) and CC versus other combined (0.474 < 1) revealed that the TT genotype has higher risk of developing DDH compared with the CC genotype. The 95 percent confidence interval of TT versus other combined and CC versus other combined is 0.932-2.891 and 0.208-1.078, respectively. For patients' and fathers' genotypes, the odds ratios of TT versus other combined (1.275 > 1) and CC versus other combined (0.815 < 1) indicate that the TT genotype has higher risk of exhibiting DDH compared to the CC genotype. For patients' and siblings' genotypes, the odds ratios of TT versus other combined (1.669) and CC versus other combined (1.048) specify that the TT genotype possesses higher risk of developing DDH compared with the CC genotype. Our study shows that there exists a relationship between GDF5 (SNP rs143383) and DDH in our population. Second, we found for the first time that the genotype TT and the T allele were overly expressed in the patients and the fathers. More studies on the confirmation of this genetic marker for DDH are called for. PMID- 29797006 TI - Autophagy in Zebrafish Extraocular Muscle Regeneration. AB - Zebrafish extraocular muscles regenerate after severe injury. Injured myocytes dedifferentiate to a mesenchymal progenitor state and reenter the cell cycle to proliferate, migrate, and redifferentiate into functional muscles. A dedifferentiation process that begins with a multinucleated syncytial myofiber filled with sarcomeres and ends with proliferating mononucleated myoblasts must include significant remodeling of the protein machinery and organelle content of the cell. It turns out that autophagy plays a key role early in this process, to degrade the sarcomeres as well as the excess nuclei of the syncytial multinucleated myofibers. Because of the robustness of the zebrafish reprogramming process, and its relative synchrony, it can serve as a useful in vivo model for studying the biology of autophagy. In this chapter, we describe the surgical muscle injury model as well as the experimental protocols for assessing and manipulating autophagy activation. PMID- 29797007 TI - High-Titer Production of HIV-Based Lentiviral Vectors in Roller Bottles for Gene and Cell Therapy. AB - Lentiviral vectors are becoming preferred vectors of choice for clinical gene therapy trials due to their safety, efficacy, and the long-term gene expression they provide. Although the efficacy of lentiviral vectors is mainly predetermined by the therapeutic genes they carry, they must be produced at high titers to exert therapeutic benefit for in vivo applications. Thus, there is need for practical, robust, and scalable viral vector production methods applicable to any laboratory setting. Here, we describe a practical lentiviral production technique in roller bottles yielding high-titer third-generation lentiviral vectors useful for in vivo gene transfer applications. CaPO4-mediated transient transfection protocol involving the use of a transfer vector and three different packaging plasmids is employed to generate lentivectors in roller bottles. Following clearance of cellular debris via low-speed centrifugation and filtration, virus is concentrated by high-speed ultracentrifugation over sucrose cushion. PMID- 29797008 TI - Direct Conversion of Mouse Embryonic Fibroblasts into Neural Crest Cells. AB - Neural crest cells (NCCs) are multipotent cells that emerge from the edges of the neural folds and extensively migrate throughout developing embryos. Dorsolaterally migrating NCCs colonize skin, differentiate into skin melanocytes, and lose their multipotency. Multipotent NCCs or NCCs derived multipotent stem cells (MSCs) were recently detected in their migrated locations, including skin, despite restrictions in cell fate acquisition following migration. Since many features of NCCs have yet to be revealed, the novel properties of NCCs represent an important and interesting field in stem cell biology. We previously reported the direct conversion of mouse embryonic fibroblasts (MEFs) into NCCs by the forced expression of the transcription factors C-MYC, KLF4, and SOX10. We herein describe the methods employed for direct conversion: retrovirus infection for the forced expression of transcription factors, a flow cytometry-sorting method for the isolation of converted NCCs, and culture methods for the maintenance and differentiation of the converted NCCs. PMID- 29797009 TI - Isolating Immune Cells from Mouse Embryonic Skin. AB - Skin is the primary barrier against the external environment and develops a robust immune network for its surveillance. The origin of the resident immune cells of the skin has become a focus of interest over past a decade. Fate mapping studies have revealed that the macrophages home into the skin as early as E12.5 and are derived from the yolk sac and fetal liver. The resident gammadeltaT cells are born in the thymus and home to the skin by E16.5. Recent work from our lab has shown that the embryonic macrophages can actively remodel the extracellular matrix in skin suggesting that the skin immune system can be activated long before exposure to foreign antigens. In this chapter, we present a detailed protocol for isolating monocytes, macrophages, and epidermal dendritic T cell populations from embryonic skin. PMID- 29797010 TI - Skin Wound Healing: Refractory Wounds and Novel Solutions. AB - This overview of the current state of skin wound healing includes in vitro and in vivo approaches along with some recent clinical trials. From an introduction to wound healing, to tissue engineering as applied to the skin, we cover the basis for the current wound care techniques as well as novel and promising approaches. Special emphasis is given to refractory wounds which include wounds in diabetic patients. Natural compounds have been ever present in wound healing, and so we devote a section to highlighting current attempts to understand their mechanisms and to use them in novel ways. PMID- 29797012 TI - EuSoMII Academy 2017. PMID- 29797013 TI - Contamination Level and Spatial Distribution of Heavy Metals in Water and Sediments of El Guajaro Reservoir, Colombia. AB - Heavy metals have become a subject of special concern worldwide, mainly due to high persistence in the environment, toxicity, biogeochemical recycling and ecological risk. Therefore, the objective of this investigation was to analyze the spatial-temporal distribution of heavy metals in water and sediments to determine the environmental status of El Guajaro Reservoir, where such studies have not been developed. Two measurement campaigns (dry and wet period) were carried out and eight sampling stations were selected. A comparison of water and sediment quality parameters with existing national and international regulations was done. Also, heavy metal distribution maps were generated, and the geoaccumulation index was calculated to identify sources and sediments contamination level. Based on the obtained results, agriculture and mining activities are the main causes of the reservoir contamination. This metals levels could be a potential risk for the aquatic life and the populations that are supplied from this water body. PMID- 29797011 TI - Xantogranulomatous pyeloneprhritis in children. AB - Xanthogranulomatous pyelonephritis (XPN) is an unusual and severe form of chronic inflammatory lesion of the kidney, characterised by the destruction of the renal parenchyma and the presence of multinucleated giant cells and lipid-laden macrophages, inflammatory infiltration and intensive renal fibrosis. There are a few cases in the literature which describe the disease in children. The pathomechanism of XPN is poorly understood. Renal obstruction with concomitant urinary tract infection is the most commonly associated pathological finding. The process is typically unilateral and may be focal or diffuse. In both cases, the perirenal infiltration is possible and can be mistaken for common renal neoplasm or inflammatory process. The symptoms are non-specific. Diagnostic imaging techniques with clinical suspicion have enabled XPN to be diagnosed and differentiated from malignancy with a high degree of confidence. Computed tomography (CT) is the mainstay of diagnostic imaging. The definitive diagnosis of XPN is based on pathological assessment after nephrectomy. We review and illustrate the clinical, radiological, surgical and pathological characteristics of XPN in children. All cases shown are surgically and histopathologically proven. TEACHING POINTS: * XPN can present different clinical manifestations. * CT is the mainstay of diagnostic imaging in XPN. * Focal type of XPN should be included in the differential diagnosis of children with a renal mass. * There are no clear guidelines on the management of XPN. * Conservative and surgical treatments should be considered for each individual case. * Histopathological examination confirms the diagnosis and excludes other benign and malign diseases. PMID- 29797015 TI - [Coding in general practice-Will the ICD-11 be a step forward?] AB - Primary care physicians in Germany don't benefit from coding diagnoses-they are coding for the needs of others. For coding, they mostly are using either the thesaurus of the German Institute of Medical Documentation and Information (DIMDI) or self-made cheat-sheets. Coding quality is low but seems to be sufficient for the main use case of the resulting data, which is the morbidity adjusted risk compensation scheme that distributes financial resources between the many German health insurance companies.Neither the International Classification of Diseases and Health Related Problems (ICD-10) nor the German thesaurus as an interface terminology are adequate for coding in primary care. The ICD-11 itself will not recognizably be a step forward from the perspective of primary care. At least the browser database format will be advantageous. An implementation into the 182 different electronic health records (EHR) on the German market would probably standardize the coding process and make code finding easier. This method of coding would still be more cumbersome than the current coding with self-made cheat-sheets.The first steps towards a useful official cheat-sheet for primary care have been taken, awaiting implementation and evaluation. The International Classification of Primary Care (ICPC-2) already provides an adequate classification standard for primary care that can also be used in combination with ICD-10. A new version of ICPC (ICPC-3) is under development. As the ICPC-2 has already been integrated into the foundation layer of ICD-11 it might easily become the future standard for coding in primary care. Improving communication between the different EHR would make taking over codes from other healthcare providers possible. Another opportunity to improve the coding quality might be creating use cases for the resulting data for the primary care physicians themselves. PMID- 29797014 TI - [The International Classification of Functioning, Disability and Health (ICF) : The implementation of the ICF Core Sets for Hand Conditions in clinical routine as an example of application]. AB - The International Classification of Functioning, Disability and Health (ICF) provides a standardized language of almost 1500 ICF categories for coding information about functioning and contextual factors. Short lists (ICF Core Sets) are helpful tools to support the implementation of the ICF in clinical routine. In this paper we report on the implementation of ICF Core Sets in clinical routine using the "ICF Core Sets for Hand Conditions" and the "Lighthouse Project Hand" as an example. Based on the ICF categories of the "Brief ICF Core Set for Hand Conditions", the ICF-based assessment tool (ICF HandA) was developed aiming to guide the assessment and treatment of patients with injuries and diseases located at the hand. The ICF HandA facilitates the standardized assessment of functioning - taking into consideration of a holistic view of the patients - along the continuum of care ranging from acute care to rehabilitation and return to work. Reference points for the assessment of the ICF HandA are determined in treatment guidelines for selected injuries and diseases of the hand along with recommendations for acute treatment and care, procedures and interventions of subsequent treatment and rehabilitation. The assessment of the ICF HandA according to the defined reference points can be done using electronic clinical assessment tools and allows for an automatic generation of a timely medical report of a patient's functioning. In the future, the ICF HandA can be used to inform the coding of functioning in ICD-11. PMID- 29797016 TI - Imaging bicipitoradial bursitis: a pictorial essay. AB - Although bicipitoradial bursitis is not commonly seen, when it does occur, it can frequently lead to diagnostic difficulty, mimicking either a soft-tissue tumor or infection. Lack of awareness of this uncommon entity can lead to unnecessary anxiety or tissue biopsy. This pictorial essay discusses the normal anatomy of the bicipitoradial bursa and the spectrum of imaging findings of bicipital bursitis. PMID- 29797017 TI - [Endoprostheses of the distal radioulnar joint]. AB - BACKGROUND: A stable distal radioulnar joint (DRUJ) is mandatory for the rotation and load transmission in the forearm and wrist. Salvage procedures such as the Darrach operation, Bowers arthroplasty, and the Kapandji-Sauve procedure include the potential risk of dynamic radioulnar instability and impingement, despite stabilizing techniques addressing the soft tissues. PROSTHESES: In an attempt to stabilize the distal forearm mechanically following ulnar head resection, various endoprostheses have been developed to replace the ulnar head. These prostheses can be used for secondary treatment of persistent complaints and unsatisfactory results after ulnar head resection, but also in the primary treatment of osteoarthritis of the DRUJ. Based on promising results concerning improvement in pain, range of motion, and grip strength, with proper indications ulnar head prostheses should be considered as a valuable treatment option for osteoarthritis of the DRUJ. PMID- 29797018 TI - [Arthroscopy of the distal radioulnar joint]. AB - OBJECTIVE: The aim of the procedure is to visualize the proximal pouch of the DRUJ, the joint surfaces of the sigmoid notch and the ulnar head, the convexity of the ulnar head and the proximal ulnar side surface of the triangular fibrocartilage complex (TFCC). INDICATIONS: Arthroscopy of the distal radioulnar joint is applied for the evaluation of joint pathologies in ulnar-sided wrist pain, especially in cases without diagnostic findings in standard X-rays and MRIs and arthroscopically assisted procedures. SURGICAL TECHNIQUE: In vertical extension, two portals of the wrist are created on the dorsal side of the DRUJ between the extensor digiti minimi and extensor carpi ulnaris tendons. By insertion of a small joint arthroscope via these portals visualization of the ulnar head, the sigmoid notch, the proximal pouch of the DRUJ and the proximal surface of the TFCC is accomplished. CONCLUSIONS: Arthroscopy of the DRUJ is a rarely and not routinely performed procedure for the diagnosis and therapy of ulnar-sided wrist pain. It is technical demanding with a flat learning curve and anatomy-related obstacles. A complete view of the joint is not always accessible. Rare complications are injuries of the extensor digiti minimi tendon, as well as contusion or sectioning of the transverse branch of the dorsal branch of the ulnar nerve. In distinct cases, this procedure offers important additional information about the distal radioulnar joint. The procedure is especially valuable for the detection of proximal TFCC injuries that are missed otherwise. PMID- 29797019 TI - [Clinical examination of the distal radioulnar joint]. AB - BACKGROUND: The distal radioulnar joint (DRUJ) provides the distal link between radius and ulnar and is the centre of rotation during pronation and supination. Pronation and supination are essential in controlling the posture and optimal presentation of the hand to grasp an object. In addition, pronation and supination enable us to rotate tools when they are in the longitudinal axis of the forearm. Due to this, the DRUJ plays a central role in the performance of activities in daily life. DIAGNOSTICS: Examination of the ulnar-side of the wrist remains challenging for hand surgeons due to a wide range of pathologies with overlapping clinical symptoms. Therefore, the clinical examination must be carried out carefully to detect the origin of the patient's complaints. Several special examination techniques are available, but their application and interpretation strongly depend on the skills and experience of the physician. Most tests are not evaluated in comparison to the gold standard of wrist arthroscopy with respect to sensitivity and specificity. The most reliable test for the DRUJ are the ulnar fovea sign, the dorsopalmar stress test and the press test. PMID- 29797020 TI - [Management and complications of tumor resections of the midface]. AB - Only about 8% of head and neck tumors affect the midface. This anatomical area is characterized by an enormous number of functionally important structures, and it is frequently only possible to achieve small resection margin distances. To avoid complications and unfavorable results, a dedicated preparation of both patient and surgeon is warranted. This review aims to provide encouragement for the postgraduate training of interested ENT specialists. Following the clinical course and based on recent literature, strategies to avoid complications of tumor surgery to the midface are given. PMID- 29797021 TI - Ambulatory blood pressure and arterial stiffness in individuals with type 1 diabetes. AB - AIMS/HYPOTHESIS: This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. METHODS: This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. RESULTS: A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p <= 0.001). In a multivariable linear regression model adjusted for age, sex, BMI, antihypertensive treatment and eGFR, masked hypertension was independently associated with higher 24 h PWV (beta 0.50 [95% CI 0.34, 0.66]), but not with PWV obtained during resting conditions (adjusted beta 0.28 [95% CI -0.53, 1.10]), using normotension as the reference group. CONCLUSIONS/INTERPRETATION: ABPM analysis revealed that one-quarter of the participants with type 1 diabetes had masked hypertension; these individuals would not have been detected by office BP alone. Moreover, arterial stiffness was increased in individuals with masked hypertension. These findings support the use of ABPM to identify individuals at risk of cardiovascular disease. PMID- 29797023 TI - ["Integrity" in the healthcare system : Recognize and avoid risks: on dealing with the Association of Statutory Health Insurance Physicians and the public prosecutors office]. AB - BACKGROUND: This article describes the introduction of the law to combat corruption in the healthcare system. OBJECTIVE: The effects of the introduced penal regulations on the delivery of medical services is critically scrutinized and the associated procedures as well as indications for the course of action are presented. RESULTS: Knowledge of the relevant regulations and types of procedure is decisive for the penal, social legislative and professional conduct risk minimization. PMID- 29797022 TI - The DPP-4 inhibitor vildagliptin impacts the gut microbiota and prevents disruption of intestinal homeostasis induced by a Western diet in mice. AB - AIMS/HYPOTHESIS: Dipeptidyl peptidase 4 (DPP-4) inhibitors are agents designed to increase the half-life of incretins. Although they are administered orally, little is known about their effects on the gut microbiota and functions, despite the fact that some bacteria present in the gut microbiota exhibit DPP-4-like activity. Our objective was to study the impact of the DPP-4 inhibitor vildagliptin on gut functions and the intestinal ecosystem in a murine model of obesity induced by a Western diet (WD). METHODS: Twenty seven male C57BL/6J mice were randomised to receive a control diet, a WD (45% kJ from fat and 17% kJ from sucrose) or a WD + vildagliptin (0.6 mg/ml in drinking water) for 8 weeks. RESULTS: Vildagliptin significantly reduced DPP-4 activity in the caecal content and faeces. Vildagliptin impacted on the composition of the gut microbiota and its metabolic activity. It mainly decreased Oscillibacter spp. (a direct effect independent of DPP-4 activity was shown on cultured O. valericigenes), increased Lactobacillus spp. and propionate, and reduced the ligands of Toll-like receptors 2 and 4. Vildagliptin protected against the reductions in crypt depth and ileal expression of antimicrobial peptides induced by the WD. In the liver, the expression of immune cell populations (Cd3g and Cd11c [also known as Itgax]) and cytokines was decreased in the WD + vildagliptin-fed mice compared with the WD fed group. Ex vivo exposure of precision-cut liver slices to vildagliptin showed that this response was not related to a direct effect of the drug on the liver tissue. CONCLUSIONS/INTERPRETATION: Our study is the first to consider the DPP-4 like activity of the gut microbiota as a target of DPP-4 inhibition. We propose that vildagliptin exerts beneficial effects at the intestinal level in association with modulation of gut microbiota, with consequences for hepatic immunity. If relevant in humans, this could open new therapeutic uses of DPP-4 inhibition to tackle gut dysfunctions in different pathophysiological contexts. DATA AVAILABILITY: The sequences used for analysis can be found in the MG-RAST database under the project name MYNEWGUT3. PMID- 29797024 TI - [Is there also a gynecologist for men? : A randomised controlled trial of AGGF information sessions in schools as a bridge to the urologist's consultations with boys]. AB - BACKGROUND: There are hardly any prevention programmes for health education and communication for boys in Germany. Boys seldom know when, how and to whom to turn to for questions or problems in the field of sexual and reproductive health. METHODS: From 2014-2016 the Medical Society for Health Promotion carried out a unique project for gender-sensitive medical health promotion for boys of all school types at 130 Bavarian schools. In 2015, 15 Bavarian schools took part in the evaluation (6th, 8th, 9th and 11th grade). At school level, similar schools have been randomised to trial and control groups. In the experimental group, three waves were conducted in panel design and two interviews were conducted in the control group using paper questionnaires. The number of cases in the panel is 599 (358 intervention group, 241 waiting control group). RESULTS: In all school types and grade levels, a highly significant increase in knowledge can be demonstrated. There is an average of 28% of the intervention group's overall knowledge improvement compared to the control group. More than 50% of the participants consider themselves to be very well informed before the intervention, although the objectively available knowledge does not justify this (e. g. average proportion of correctly answered questions on male anatomy and physiology 0.7 out of 6). The participants rate the medical information sessions and the fact that they are conducted by doctors with 1.7 or 1.6 (1: very good, to 5: poor). DISCUSSION: Boys urgently need proper knowledge transfer in the field of sexual health. They benefit regardless of the types of school from these health information sessions. The gender-sensitive and socially compensatory medical information sessions are highly accepted, effective and serve as a bridge to the general practitioners. A nationwide establishment of the intervention seems thus absolutely necessary. PMID- 29797025 TI - [Percutaneous CT-guided radiofrequency ablation for small renal masses : A retrospective, single center data analysis]. AB - BACKGROUND: The incidence of small renal masses has increased in recent decades. Standard surgical treatment may not be applicable in patients with advanced age or severe comorbidities. Therefore, minimally invasive therapeutic approaches, such as radiofrequency ablation (RFA), may be a therapeutic option for such patients. OBJECTIVES: Assessment of oncological and functional outcomes of percutaneous RFA in small renal masses. MATERIALS AND METHODS: Single center evaluation of all RFA performed at the hospital Landesklinikum Baden from 2006 2016. RESULTS: A total of 98 RFA were performed in 85 patients. Mean patient age was 69.5 years. Median tumor size was 26.2 mm, while the length of hospital stay was 1.4 days. Overall, 96.8% of RFA procedures were considered to be technically complete. Recurrence rate was 17.5%. Most of the recurrences were treated via a second RFA. Complication rates were fairly low as the vast majority of ablations were free of complications (82.7%). Grade I, II and III complications (according to the Clavien-Dindo classification) occurred in 13.3%, 3% and 1%, respectively. A significant deterioration of renal function due to RFA was not observed. Cancer specific survival rate for renal cell carcinoma was 100%; overall survival was 84.7% after an average follow-up period of more than 3 years. CONCLUSION: RFA is an adequate alternative treatment option for small renal masses in patients unfit to undergo surgical excision. Patients benefit from the low complication rates, preservation of renal function, and short hospital stays. PMID- 29797028 TI - ECDC definitions and methods for the surveillance of healthcare-associated infections in intensive care units. PMID- 29797027 TI - Di-(2-ethylhexyl) Phthalate Exposure Modulates Antioxidant Enzyme Activity and Gene Expression in Juvenile and Adult Daphnia magna. AB - Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in the polyvinyl chloride industry worldwide. DEHP exists in the aquatic environments for decades. However, the toxicological effects of DEHP to aquatic organisms have not been adequately researched. We investigated acute toxicity, oxidative damage, antioxidant enzyme activities, and gene expression patterns of antioxidant enzymes in juvenile and adult Daphnia magna exposed to DEHP. We found that the median lethal concentrations (LC50) of DEHP for juveniles exposed for 24 and 48 h were 0.83 and 0.56 mg L-1, respectively. The LC50 of DEHP in adults exposed for 24 and 48 h were 0.48 and 0.35 mg L-1. Daphnia magna that was exposed to DEHP had increased malondialdehyde levels for 24 h and lower total antioxidant capacity compared with the control. Activity levels of antioxidant enzymes superoxide dismutase and phase II detoxifying enzyme glutathione S-transferases were significantly higher upon initial exposure for 24 h, and enzyme activity was then diminished at high concentrations and prolonged exposure for 48 h. Gene expression levels of cat and gst were notably reduced or increased upon DEHP exposure. These findings suggest that DEHP can cause biochemical and physiological effects in juvenile and adult D. magna by inhibiting enzymes, an increase in lipid peroxidation levels and changes both transcription levels of enzymes (cat, gst). On the whole, juveniles and adults both responded similarly to DEHP. Our findings will contribute to the understanding of toxic mechanisms in phthalate esters and the evaluation of environmental risks in aquatic ecosystems. PMID- 29797026 TI - Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis. AB - In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term 'danger responses'. Danger signals are generated when primitive 'pattern recognition receptors' (PRR) encounter activating 'alarmins'. These molecular species may be of pathogenic infective origin (pathogen associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major. PMID- 29797029 TI - The "Christmas tree" bladder. PMID- 29797030 TI - Factors predicting intolerance to definitive conventional radiotherapy in geriatric patients. AB - PURPOSE: Although radiotherapy can be administered with a relatively low therapeutic burden, many elderly patients do not complete radiotherapy. In order to predict intolerance during radiotherapy, this study retrospectively analyzed the frequency of and risk factors for radiotherapy interruption among geriatric patients. METHODS: From September 2009 to December 2016, 353 patients aged >=70 years received definitive radiotherapy with a conventionally fractionated schedule. "Total interruption" included completion of <=90% of a planned radiotherapy, temporary discontinuation, and treatment-related mortality within 2 months. "Early-phase incompletion" and "mid-phase incompletion" represented completion of <=50 and <=80% of a planned radiotherapy, respectively. RESULTS: The median age of patients was 74 years. Early- and mid-phase incompletions and total interruption occurred in 4.2, 9.3, and 19.3% of patients, respectively. Total interruption occurred frequently in cancers involving the thorax (27.4%), head and neck (23.1%), abdomen (20.0%), pelvis (17.4%), and breast/extremity (8.1%). The Eastern Cooperative Oncology Group (ECOG) performance score (P = 0.004 and 0.002), serum albumin level (P = 0.016 and 0.002), and the expected 5 year survival (P = 0.033 and 0.034) were significant factors for mid-phase incompletion and total interruption. Age >= 75 years (P = 0.008), concurrent chemotherapy (P = 0.017), and the extent of radiation field (P = 0.027) were factors associated with total interruption. CONCLUSION: Overall, 19.3% of the elderly patients showed treatment intolerance during conventional radiotherapy. Serum albumin level and ECOG performance score should be considered as surrogate markers for radiotherapy interruption prior to the decision regarding definite conventional radiotherapy. PMID- 29797032 TI - [Acupuncture techniques in professional football]. AB - The number of scientific studies about acupuncture has increased significantly during recent years. Acupuncture can be used as an evidence-based adjunct therapy for a variety of indications in professional football. This review summarizes various acupuncture techniques and related techniques for utilization in the field of professional soccer. Besides knee, shoulder, spinal, elbow and postoperative pain, scientific meta-analyses also point towards the effectiveness of acupuncture in ankle sprains, allergic rhinoconjunctivitis and nausea. Dry needling is an emerging option for treatment of myofascial trigger points and could potentially result in improved prevention of muscular injuries and enhancement of muscular performance. PMID- 29797033 TI - [Quantification of treatment success for geriatric sacral fractures]. AB - BACKGROUND: Geriatric sacral fractures represent an independent fracture entity of increasing incidence and growing socioeconomic relevance. The goals of treatment are very different to those in younger patients with high-energy pelvic fractures. Hence, new outcome measurement instruments are required in order to assess the success of treatment. OBJECTIVE: Literature review summarizing existing concepts and providing an overview of outcome measurement instruments for geriatric sacral fractures. METHODS: Narrative review article based on an analysis of the German and English-speaking literature from the last 10 years. RESULTS: Geriatric sacral fractures result in impaired mobility, increased physical and social loss of dependency and increased morbidity and mortality rates. There is a lack of standardized specific assessment procedures for functional outcome measurement after geriatric sacral fractures. Until these are developed and validated, a parallel acquisition of mortality, the timed up and go test, the Oswestry disability index (ODI) and a generic healthcare questionnaire score (SF-36, EQ-5D) seem to be most suitable. CONCLUSION: At present our knowledge about the natural course of geriatric sacral fractures is limited by the lack of well-validated instruments to measure functional and radiographic outcomes. This has to be considered when evaluating the success of new treatment options for these patients. Future studies should validate existing scores for this population and develop new specific outcome instruments. PMID- 29797031 TI - [Prehospital application of tourniquets for life-threatening extremity hemorrhage : Systematic review of literature]. AB - INTRODUCTION: The effectiveness of a tourniquet in the case of life-threatening hemorrhages of the extremities is well recognized and led to the recommendations on "Tourniquet" of the German Society of Anaesthesiology and Intensive Care (DGAI) in 2016. The aim of this systematic review was to re-evaluate the current medical literature in relation to the published DGAI recommendations. MATERIAL AND METHODS: Based on the analysis of all studies published from January 2015 until January 2018 in the PubMed databases, the publicized recommendations for action on "Tourniquet" of the DGAI were critically re-evaluated. For this purpose, 17 questions on 6 subjects were formulated in advance. The systematic review followed the PRISMA recommendations and is registered in PROSPERO (International prospective register of systematic reviews, Reg.-ID: CRD42018091528). RESULTS: Of the 284 studies identified with the keywords tourniquet and trauma in the period from January 2015 to January 2018 in PubMed, 50 original papers discussing the prehospital application of tourniquet for life threatening hemorrhage of the extremities were included. The overall level of evidence is low. No article addressed any of the formulated questions with a prospective randomized interventional study. Scientific deductions could be found only in an indirect way in a descriptive manner. CONCLUSION: The 50 original articles included in this qualitative, systematic review revealed that the recommendations "Tourniquet" of the DGAI published in 2016 are mostly still up to date despite an inhomogeneous study situation. A deviation occurred in the conversion of a tourniquet but due to the short prehospital treatment time in the civilian setting this is of little importance; however, in the future a strict distinction should be made between tourniquets which were placed for tactical reasons and those placed as a medical necessity. PMID- 29797034 TI - Combination of all-stage and high-temperature adult-plant resistance QTL confers high-level, durable resistance to stripe rust in winter wheat cultivar Madsen. AB - KEY MESSAGE: Wheat cultivar Madsen has a new gene on the short arm of chromosome 1A and two QTL for all-stage resistance and three QTL for high-temperature adult plant resistance that in combination confer high-level, durable resistance to stripe rust. Wheat cultivar Madsen has maintained a high-level resistance to stripe rust over 30 years. To map quantitative trait loci (QTL) underlying the high-level, durable resistance, 156 recombinant inbred lines (RILs) developed from cross Avocet S * Madsen were phenotyped with selected races of Puccinia striiformis f. sp. tritici in the greenhouse seedling tests, and in naturally infected fields during 2015-2017. The RILs were genotyped by SSR and SNP markers from genotyping by sequencing and the 90 K wheat SNP chip. Three QTL for all stage resistance were mapped on chromosomes 1AS, 1BS and 2AS, and two QTL for high-temperature adult-plant (HTAP) resistance were mapped on 3BS and 6BS. The most effective QTL on 2AS, explaining 8.97-23.10% of the phenotypic variation in seedling tests and 8.60-71.23% in field tests, contained Yr17 for all-stage resistance and an additional gene for HTAP resistance. The 6BS QTL, detected in all field tests, was identified as Yr78. The 1AS QTL, conferring all-stage resistance, was identified as a new gene, which explained 20.45 and 30.23% of variation in resistance to races PSTv-37 and PSTv-40, respectively, and contributed significantly to field resistance at Pullman in 2015-2017, but was not detected at Mount Vernon. The interactions among QTL were mostly additive, and RILs with all five QTL had the highest level of resistance in the field, similar to Madsen. Genotyping 148 US Pacific Northwest wheat cultivars with markers for the 1AS, 2AS and 6BS QTL validated the genes and markers, and indicated their usefulness for marker-assisted selection. PMID- 29797035 TI - Pharmacokinetics of imipenem in plasma and cerebrospinal fluid in patients with intracerebral hemorrhage. PMID- 29797037 TI - Constant inhibition in congenital lower extremity shortening: does it begin in utero? AB - BACKGROUND: Limb-length discrepancy (LLD) in children with congenital lower extremity shortening is constant in proportion from birth to skeletal maturity (known as constant inhibition), but its developmental pattern in utero is unknown. The popular prenatal multiplier method to predict LLD at birth assumes constant inhibition in utero to be true. Verifying the in utero developmental pattern of LLD, and thus confirming the validity of the prenatal multiplier method, is crucial for meaningful prenatal parental counseling. OBJECTIVE: To elucidate the in utero developmental pattern of LLD in fetuses with congenital lower extremity shortening. MATERIALS AND METHODS: Clinical indications for 3,605 lower extremity radiographs performed on infants (<1 year old) at a large tertiary hospital over a 17-year period were reviewed. Inclusion criteria were (1) diagnosis of congenital lower extremity shortening, (2) bilateral lower limb postnatal radiographs documenting LLD and (3) fetal ultrasound (US) documenting LLD. Available measurements of femoral, tibial and fibular lengths on fetal US and postnatal radiographs were collected. Prenatal and postnatal length ratios of shorter-to-longer bones were calculated and compared. RESULTS: Eighteen infants met inclusion criteria. Diagnoses were proximal focal femoral deficiency=4, congenital short femur=2, tibial hemimelia=3, posteromedial tibial bowing=6 and fibular hemimelia=3. The correlations between postnatal and prenatal length ratios were high for the femur, tibia and fibula (R>0.98, P<0.0001). The relative differences in the postnatal and prenatal length ratios of these bones were small (|average|<0.026, standard deviation <0.068). CONCLUSION: Our data indicate that the postnatal and prenatal length ratios were equivalent, supporting the constant inhibition pattern of LLD in utero, thus validating the prenatal multiplier method for predicting LLD. PMID- 29797036 TI - Comparative safety and efficacy of balloon use in air enema reduction for pediatric intussusception. AB - BACKGROUND: Intussusception, a common cause of bowel obstruction in young children, is primarily treated with air enema reduction. There is little literature comparing the safety and efficacy of air reduction without or with a rectal balloon. OBJECTIVE: To determine the safety and efficacy of a rectal balloon seal in air enema reduction. MATERIALS AND METHODS: We retrospectively reviewed the records of children who underwent air reduction for ileocolic or ileo-ileocolic intussusception over an 8-year period. We sorted data from 566 children according to whether a rectal balloon was used in the reduction, and further sorted them by type and experience level of the practitioner. Using logistic regression analyses, we identified risk factors for iatrogenic bowel perforation or failed reduction. RESULTS: Significant associations with bowel perforation included balloon use (P=0.038), age <1 year (P<0.0001), and attending physician's level of experience <5 years (P=0.043). Younger age was associated with both perforation (P<0.0001) and procedural failure (P=0.001). The risk adjusted predicted probability of perforation decreased with age, approaching zero by 10 months regardless of balloon use. For cases without bowel resection, the risk-adjusted predicted probability of failure decreased toward zero by 30 months with balloon use, while remaining constant at 3-12% regardless of age when not using a balloon. CONCLUSION: The likelihood of a successful air reduction might be safely increased by using an inflated rectal balloon in children older than 9 months. Use of a balloon in younger infants is associated with a higher risk of iatrogenic bowel injury. PMID- 29797038 TI - Metrology for stable isotope reference materials: 13C/12C and 18O/16O isotope ratio value assignment of pure carbon dioxide gas samples on the Vienna PeeDee Belemnite-CO2 scale using dual-inlet mass spectrometry. AB - Isotope ratio measurements have been conducted on a series of isotopically distinct pure CO2 gas samples using the technique of dual-inlet isotope ratio mass spectrometry (DI-IRMS). The influence of instrumental parameters, data normalization schemes on the metrological traceability and uncertainty of the sample isotope composition have been characterized. Traceability to the Vienna PeeDee Belemnite(VPDB)-CO2 scale was realized using the pure CO2 isotope reference materials(IRMs) 8562, 8563, and 8564. The uncertainty analyses include contributions associated with the values of iRMs and the repeatability and reproducibility of our measurements. Our DI-IRMS measurement system is demonstrated to have high long-term stability, approaching a precision of 0.001 parts-per-thousand for the 45/44 and 46/44 ion signal ratios. The single- and two point normalization bias for the iRMs were found to be within their published standard uncertainty values. The values of 13C/12C and 18O/16O isotope ratios are expressed relative to VPDB-CO2 using the [Formula: see text] and [Formula: see text] notation, respectively, in parts-per-thousand (0/00 or per mil). For the samples, value assignments between (-25 to +2) 0/00 and (-33 to -1) 0/00 with nominal combined standard uncertainties of (0.05, 0.3) 0/00 for [Formula: see text] and [Formula: see text], respectively were obtained. These samples are used as laboratory reference to provide anchor points for value assignment of isotope ratios (with VPDB traceability) to pure CO2 samples. Additionally, they serve as potential parent isotopic source material required for the development of gravimetric based iRMs of CO2 in CO2-free dry air in high pressure gas cylinder packages at desired abundance levels and isotopic composition values. Graphical abstract CO2 gas isotope ratio metrology. PMID- 29797039 TI - [Imaging of abdominal tumors in childhood and adolescence : Part I: Background, hepatic, splenic and pancreatic tumors]. AB - In comparison to adult patients, other specific entities of abdominal tumors occur in childhood and adolescence. These include malignant tumors originating from embryonic tissue, such as hepatoblastoma. Some of the abdominal tumors are already diagnosed prenatally or in neonates. Sonography functions as the primary radiological basic diagnostics of pediatric abdominal space-occupying lesions, if necessary supplemented by administration of ultrasound contrast medium or the implementation of novel techniques (e.g. innovative Doppler and elastography procedures). Magnetic resonance imaging (MRI) is used for a comprehensive and detailed depiction of the tumors including the question of resectability and vascular supply. Various weighting and different MRI sequences are used in order to be able to assess the signal behavior of the tumor and therefore the possible presence of calcification, necrosis or hemorrhage, the behavior of dynamic contrast enhancement, and the presence and extent of diffusion disorders. This information is decisive in order to be able to assess the entity and malignancy of the abdominal space-occupying lesion. Rare but relevant tumors with respect to the entity occur in childhood and adolescence in the abdominal organs liver, spleen and pancreas. PMID- 29797040 TI - [Dandy-Walker malformation]. AB - The Dandy-Walker malformation is the most frequent cerebral malformation. It is defined by hypoplasia and upward rotation of the vermis cerebelli, a cystic enlargement of the fourth ventricle and in total an enlarged posterior fossa with cranially shifted position of the lateral sinus, tentorium and torcula herophili. This malformation was first described by Dandy and Blackfan in 1914 then supplemented again by Taggart and Walker in 1942. The current description as Dandy-Walker malformation was introduced in 1954 by Bender. In addition to these classical findings, the Dandy-Walker malformation is characterized by other abnormalities and malformations of the central nervous system (CNS) including agenesis of the corpus callosum, heterotopia, occipital meningocele, visual deficits and epilepsy. Neurogenetic and imaging examinations have led to a better understanding of this malformation. PMID- 29797042 TI - [Contrast-enhanced ultrasound: Tingling]. PMID- 29797041 TI - [Spina bifida]. AB - Spina bifida is a congenital disorder with incomplete closure of the spinal column due to a bony vertebral defect. The term spina bifida literally means cleft spine and is used as a generic term of spinal dysraphism (Greek: Raphe = seam). It is a midline defect that occurs during the embryonic period. The insufficient closure of one or more vertebral arches is the result of an incomplete junction of the neural tube. Depending on the extent of the neural tube defect, various types of spina bifida can be differentiated. Closed spinal dysraphisms, also known as spina bifida occulta, are solely characterized by a bony defect of the vertebral arch, whereas, spina bifida cystica (synonym: open spina bifida or spina bifida aperta) can be distinguished by a protruding cyst, containing either meninges or meninges in combination with spinal cord tissue and are defined as open spinal dysraphisms. PMID- 29797044 TI - Interaction dynamics between grouping principles in touch: phenomenological and psychophysical evidence. AB - In two experiments, we investigated the interactions between the grouping principles of spatial proximity and texture similarity in touch. For that purpose, we adapted to touch two paradigms widely employed in vision. In Experiment 1, we used an experimental phenomenological task consisting of rating the strength of grouping in both acting alone and conjoined cooperative and competitive conditions. In Experiment 2, participants performed a psychophysical task in which an objective (in)correct response was defined by selectively attending to one grouping cue in different blocks of trials. The results showed that spatial proximity dominated over texture similarity when the two principles were conjoined in competition. In addition, the present results are compatible with an additive model of grouping effects as indicated by the greater grouping effect in the cooperative condition and the smaller grouping effect in the competitive condition relative to a.0cting alone grouping principles. The similarities and differences between vision and touch are discussed. PMID- 29797043 TI - [Contrast-enhanced ultrasound (CEUS) and image fusion for procedures of liver interventions]. AB - CLINICAL/METHODICAL ISSUE: Contrast-enhanced ultrasound (CEUS) is becoming increasingly important for the detection and characterization of malignant liver lesions and allows percutaneous treatment when surgery is not possible. Contrast enhanced ultrasound image fusion with computed tomography (CT) and magnetic resonance imaging (MRI) opens up further options for the targeted investigation of a modified tumor treatment. METHODICAL INNOVATIONS: Ultrasound image fusion offers the potential for real-time imaging and can be combined with other cross sectional imaging techniques as well as CEUS. PERFORMANCE: With the implementation of ultrasound contrast agents and image fusion, ultrasound has been improved in the detection and characterization of liver lesions in comparison to other cross-sectional imaging techniques. In addition, this method can also be used for intervention procedures. The success rate of fusion-guided biopsies or CEUS-guided tumor ablation lies between 80 and 100% in the literature. ACHIEVEMENTS: Ultrasound-guided image fusion using CT or MRI data, in combination with CEUS, can facilitate diagnosis and therapy follow-up after liver interventions. PRACTICAL RECOMMENDATIONS: In addition to the primary applications of image fusion in the diagnosis and treatment of liver lesions, further useful indications can be integrated into daily work. These include, for example, intraoperative and vascular applications as well applications in other organ systems. PMID- 29797045 TI - Priming by motivationally salient distractors produces hemispheric asymmetries in visual processing. AB - Stimuli that reliably herald the availability of rewards or punishers can acquire value associations, potentially imbuing them with emotional significance and attentional prioritization. Previous work has shown that an emotional stimulus (prime) presented just prior to an attention-demanding task disrupts performance in a lateralized manner that is independent of the prime's emotional valence. Here, we asked whether neutral stimuli with acquired value associations would similarly disrupt attention. In two experiments, adult participants first learned to associate specific face or chair stimuli with a high or low probability of either winning or losing points. These conditioned stimuli then served as primes in a speeded letter-search task. Primes with high versus low outcome probability, regardless of valence, slowed search for targets appearing in the left but not the right visual hemifield, mirroring previous results using emotional primes, and suggesting that motivational mechanisms that compete for control with non emotional cognitive processes are right-lateralized in the human brain. PMID- 29797046 TI - [Journal Club]. PMID- 29797050 TI - Distance to hospital is not a risk factor for emergency colon cancer surgery. AB - PURPOSE: The purpose of this study is to see if the distance to a hospital performing colon cancer surgery is a risk factor for emergency surgical intervention and to determine the variability between defined but demographically divergent catchment areas. METHODS: Data on patients living in Vasterbotten County who underwent colon cancer surgery between 2007 and 2010 were extracted from the Swedish Colorectal Cancer Register (SCRCR). Of the 436 registrations matching these criteria, 380 patients were used in the analysis, and their distance to the nearest hospital providing care for colorectal cancer (CRC) was estimated using Google MapsTM. The correlations between the risk for emergency surgery and the distance to a hospital, gender, age, income level and hospital catchment area were analysed in uni- and multivariate models. RESULTS: Distance to the nearest hospital had no significant effect on the proportion of emergency operations for colon cancer. There was significant variability in risk for emergency surgery between hospital catchment areas, where the catchment areas of the university hospital and the most rural hospital had a higher proportion than the other local hospital catchment area (OR, 2.00 (p = 0.038) and OR, 2.97 (p = 0.005)). These results were still significant when analysed with multivariate logistic regression (OR, 2.13 (p = 0.026) and OR, 3.05 (p = 0.013)). CONCLUSION: Distance to a hospital performing colon cancer surgery had no effect on the proportion of emergency surgeries. However, a variability between defined catchment areas was seen. Future studies will focus on possible factors behind this variability. PMID- 29797048 TI - Engineering herbicide-resistant watermelon variety through CRISPR/Cas9-mediated base-editing. PMID- 29797049 TI - Successful overexpression of wild-type inhibitor-2 of PP1 in cardiovascular cells. AB - About half of the cardiac serine/threonine phosphatase activity is due to the activity of protein phosphatase type 1 (PP1). The activity of PP1 can be inhibited by an endogenous protein for which the expression inhibitor-2 (I-2) has been coined. We have previously described a transgenic mouse overexpressing a truncated form of I-2. Here, we have described and initially characterized several founders that overexpress the non-truncated (i.e., full length) I-2 in the mouse heart (TG) and compared them with non-transgenic littermates (WT). The founder with the highest overexpression of I-2 displayed under basal conditions no difference in contractile parameters (heart rate, developed tension, and its first derivate) compared to WT. The relative level of PP1 inhibition was similar in mice overexpressing the non-truncated as well as the truncated form of I-2. For comparison, we overexpressed I-2 by an adenoviral system in several cell lines (myocytes from a tumor-derived cell line (H9C2), neonatal rat cardiomyocytes, smooth muscle cells from rat aorta (A7R5)). We noted gene dosage dependent staining for I-2 protein in infected cells together with reduced PP1 activity. Finally, I-2 expression in neonatal rat cardiomyocytes led to an increase of Ca2+ transients by about 60%. In summary, we achieved immunologically confirmed overexpression of wild-type I-2 in cardiovascular cells which was biochemically able to inhibit PP1 in the whole heart (using I-2 transgenic mice) as well as in isolated cells including cardiomyocytes (using I-2 coding virus) indirectly underscoring the importance of PP1 for cardiovascular function. PMID- 29797047 TI - Physcomitrella patens, a versatile synthetic biology chassis. AB - KEY MESSAGE: During three decades the moss Physcomitrella patens has been developed to a superb green cell factory with the first commercial products on the market. In the past three decades the moss P. patens has been developed from an obscure bryophyte to a model organism in basic biology, biotechnology, and synthetic biology. Some of the key features of this system include a wide range of Omics technologies, precise genome-engineering via homologous recombination with yeast-like efficiency, a certified good-manufacturing-practice production in bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein products, superb product stability from batch-to-batch, and a reliable procedure for cryopreservation of cell lines in a master cell bank. About a dozen human proteins are being produced in P. patens as potential biopharmaceuticals, some of them are not only similar to their animal-produced counterparts, but are real biobetters with superior performance. A moss-made pharmaceutical successfully passed phase 1 clinical trials, a fragrant moss, and a cosmetic moss product is already on the market, highlighting the economic potential of this synthetic biology chassis. Here, we focus on the features of mosses as versatile cell factories for synthetic biology and their impact on metabolic engineering. PMID- 29797051 TI - Limits of noise for autoregulated gene expression. AB - Gene expression is influenced by extrinsic noise (involving a fluctuating environment of cellular processes) and intrinsic noise (referring to fluctuations within a cell under constant environment). We study the standard model of gene expression including an (in-)active gene, mRNA and protein. Gene expression is regulated in the sense that the protein feeds back and either represses (negative feedback) or enhances (positive feedback) its production at the stage of transcription. While it is well-known that negative (positive) feedback reduces (increases) intrinsic noise, we give a precise result on the resulting fluctuations in protein numbers. The technique we use is an extension of the Langevin approximation and is an application of a central limit theorem under stochastic averaging for Markov jump processes (Kang et al. in Ann Appl Probab 24:721-759, 2014). We find that (under our scaling and in equilibrium), negative feedback leads to a reduction in the Fano factor of at most 2, while the noise under positive feedback is potentially unbounded. The fit with simulations is very good and improves on known approximations. PMID- 29797053 TI - Correction to: Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis. AB - The original publication of this paper contain an error because of an incorrect captured corresponding author. PMID- 29797055 TI - ICD lead type and RV lead position in CRT-D recipients. AB - BACKGROUND: Data on preferred ICD lead type and optimal RV lead position in patients undergoing CRT-D implantation are limited. OBJECTIVES: To compare dual- versus single-coil ICD leads and non-apical versus apical RV lead position and their impact on clinical parameters and survival in CRT-D recipients. METHODS: A total of 563 consecutive patients with advanced heart failure and indication for CRT-D implantation were enrolled in two European tertiary centers. Endpoints were improvement in NYHA functional class, changes in echo- and electrocardiographic parameters, and all-cause and cardiovascular mortality. RESULTS: In this retrospective analysis, a total of 313 (56%) dual- and 250 (44%) single-coil ICD leads were used. RV leads were placed non-apically in 262 (47%) and apically in 296 (53%) patients, respectively. Over a mean follow-up of 41 +/- 34 months, all cause mortality and cardiovascular mortality were similar for patients with dual- versus single-coil ICD lead (adjusted HR 0.81, 95% CI 0.58-1.12 and aHR 1.22, 95% CI 0.73-2.04) and non-apical versus apical RV lead position (aHR 0.98, 95% CI 0.71-1.36 and aHR 0.76, 95% CI 0.44-1.31). Non-apical RV lead position was associated with greater reduction in QRS duration after CRT implantation (- 14.4 +/- 32.1 vs. - 4.3 +/- 34.3 ms, p < 0.001). CONCLUSIONS: We found no association between ICD lead type or RV lead position and outcomes in CRT-D recipients. Non apical RV lead position was associated with larger reduction in QRS duration. PMID- 29797054 TI - Value of the CHA2DS2-VASc score and Fabry-specific score for predicting new-onset or recurrent stroke/TIA in Fabry disease patients without atrial fibrillation. AB - OBJECTIVES: To evaluate potential risk factors for stroke or transient ischemic attacks (TIA) and to test the feasibility and efficacy of a Fabry-specific stroke risk score in Fabry disease (FD) patients without atrial fibrillation (AF). BACKGROUND: FD patients often experience cerebrovascular events (stroke/TIA) at young age. METHODS: 159 genetically confirmed FD patients without AF (aged 40 +/- 14 years, 42.1% male) were included, and risk factors for stroke/TIA events were determined. All patients were followed up over a median period of 60 (quartiles 35-90) months. The pre-defined primary outcomes included new-onset or recurrent stroke/TIA and all-cause death. RESULTS: Prior stroke/TIA (HR 19.97, P < .001), angiokeratoma (HR 4.06, P = .010), elevated creatinine (HR 3.74, P = .011), significant left ventricular hypertrophy (HR 4.07, P = .017), and reduced global systolic strain (GLS, HR 5.19, P = .002) remained as independent risk predictors of new-onset or recurrent stroke/TIA in FD patients without AF. A Fabry-specific score was established based on above defined risk factors, proving somehow superior to the CHA2DS2-VASc score in predicting new-onset or recurrent stroke/TIA in this cohort (AUC 0.87 vs. 0.75, P = .199). CONCLUSIONS: Prior stroke/TIA, angiokeratoma, renal dysfunction, left ventricular hypertrophy, and global systolic dysfunction are independent risk factors for new-onset or recurrent stroke/TIA in FD patients without AF. It is feasible to predict new or recurrent cerebral events with the Fabry-specific score based on the above defined risk factors. Future studies are warranted to test if FD patients with high risk for new-onset or recurrent stroke/TIA, as defined by the Fabry-specific score (>= 2 points), might benefit from antithrombotic therapy. Clinical trial registration HEAL-FABRY (evaluation of HEArt invoLvement in patients with FABRY disease, NCT03362164). PMID- 29797057 TI - Koroska 8000 Himalayan expedition: digit responses to cold stress following ascent to Broadpeak (Pakistan, 8051 m). AB - PURPOSE: Cold-induced vasodilatation (CIVD) is a peripheral blood flow response, observed in both the hands and feet. Exercise has been shown to enhance the response, specifically by increasing mean skin temperatures (Tsk), in part due to the increased number of CIVD waves. In contrast, hypobaric hypoxia has been suggested to impair digit skin temperature responses, particularly during subsequent hand rewarming following the cold stimulus. This study examined the combined effect of exercise and hypobaric hypoxia on the CIVD response. We compared the CIVD responses in the digits of both the hands and feet of a team of alpinists (N = 5) before and after a 35-day Himalayan expedition to Broadpeak, Pakistan (8051 m). METHODS: Five elite alpinists participated in hand and foot cold water immersion tests 20 days before and immediately upon return from their expedition. RESULTS: The alpinists summited successfully without supplemental oxygen. Post-expedition, all alpinists demonstrated higher minimum Tsk in their hands (pre: 9.9 +/- 1.1, post: 10.1 +/- 0.7 degrees C, p = 0.031). Four alpinists had either greater CIVD waves, and, consequently, higher mean Tsk in their hands, or higher recovery temperatures (pre: 26.0 +/- 5.5 degrees C post: 31.0 +/- 4.1 degrees C, p = 0.052), or faster rewarming rate (pre: 2.6 +/- 0.5 degrees C min-1 post: 3.1 +/- 0.4 degrees C min-1,p = 0.052). In the feet, the responses varied: 1/5 had higher wave amplitudes and 1/5 had higher passive recovery temperatures, whereas 3/5 had lower mean toe temperatures during cold exposure. CONCLUSIONS: The results of the cold stress test suggest after a 35-day Himalayan expedition, alpinists experienced a slight cold adaptation of the hands, but not the feet. PMID- 29797056 TI - Diffusion kurtosis imaging in the characterisation of rectal cancer: utilizing the most repeatable region-of-interest strategy for diffusion parameters on a 3T scanner. AB - OBJECTIVES: Our goal was to investigate the correlation between histopathology and diffusion parameters by utilising the most repeatable region-of-interest (ROI) strategy for diffusion parameters in rectal cancer on a 3T scanner. METHODS: 113 patients underwent DKI-MR and 66 of these patients received surgery without neoadjuvant chemoradiotherapy. Two readers independently measured the parameters using three slice protocols including single slice, three slices and whole-tumour slice (WTS), combined with one of two ROIs, including outline and round ROI. ANOVA, Kruskal-Wallis, a paired sample t-test, interclass correlation coefficient (ICC), Bland-Altman, Student's t-tests, receiver operating characteristic curves and z statistic were used for statistical analysis. RESULTS: There were no significant differences among the three slice protocols in ADC values (p = 0.822, 0.987), K values (p = 0.842, 0.859) and D values (p = 0.917, 0.988) using round and outline ROI, respectively. The ADC and D values derived from outline ROIs were higher than those from round ROIs (all p < 0.001 for ADC, all p < 0.001 for D), while K values derived from outline ROIs were lower than those from round ROIs (p < 0.001, p = 0.001, p < 0.001) using three slice protocols, respectively. The WTS-outline ROI resulted in the best intra- and inter-observer ICC. Utilising the WTS-outline ROI method, the AUC for assessment of well-differentiated tumours was 0.871 by K and 0.809 by ADC; and the AUC for T2 was 0.768 by K. CONCLUSIONS: The most repeatable strategy was the WTS-outline ROI method. In addition to DWI, DKI also have diagnostic value for rectal cancer histopathological characteristics utilising the WTS-outline ROI on a 3T scanner. KEY POINTS: * DKI using a 3T scanner is feasible for assessing rectal cancer. * ROI and slice protocol show considerable influence on DKI parameters. * DKI parameters exhibit excellent repeatability using whole-tumour slice-outline ROI on 3T scanner. * DKI has considerable diagnostic value for the estimation of rectal cancer characteristics. PMID- 29797052 TI - Mammalian urine concentration: a review of renal medullary architecture and membrane transporters. AB - Mammalian kidneys play an essential role in balancing internal water and salt concentrations. When water needs to be conserved, the renal medulla produces concentrated urine. Central to this process of urine concentration is an osmotic gradient that increases from the corticomedullary boundary to the inner medullary tip. How this gradient is generated and maintained has been the subject of study since the 1940s. While it is generally accepted that the outer medulla contributes to the gradient by means of an active process involving countercurrent multiplication, the source of the gradient in the inner medulla is unclear. The last two decades have witnessed advances in our understanding of the urine-concentrating mechanism. Details of medullary architecture and permeability properties of the tubules and vessels suggest that the functional and anatomic relationships of these structures may contribute to the osmotic gradient necessary to concentrate urine. Additionally, we are learning more about the membrane transporters involved and their regulatory mechanisms. The role of medullary architecture and membrane transporters in the mammalian urine concentrating mechanism are the focus of this review. PMID- 29797059 TI - Clinical characteristics and cardiovascular outcomes in patients with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF Registry. AB - Management of atrial fibrillation (AF) with current rhythm-control therapy has an uncertain impact on outcomes. Among 3731 patients in the Fushimi AF Registry, a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, we investigated the characteristics and outcomes in 478 patients receiving rhythm control therapy (anti-arrhythmic drug and/or catheter ablation) alone, with 1279 patients receiving rate-control therapy (beta-blockers, calcium channel blockers, and digoxin) alone serving as a reference. The Rhythm-control group, 26% of which had prior catheter ablation, was younger (70.5 +/- 10.8 vs. 74.3 +/- 10.4 years, P < 0.001) with lower CHA2DS2-VASc score (2.71 +/- 1.63 vs. 3.64 +/- 1.62, P < 0.001) and received oral anticoagulants less frequently than the Rate-control group. During the median follow-up of 1107 days, the incidence of the composite of cardiac death and heart failure (HF) hospitalization was lower with rhythm control (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.14-0.36; P < 0.001), whereas that of ischemic stroke/systemic embolism was not significantly different (HR 0.64, 95% CI 0.35-1.10; P = 0.12), when compared to rate control. Propensity score-matching analysis as well as multivariate analysis further supported the relation of Rhythm-control group to the lower incidence of the composite of cardiac death and HF hospitalization. Rhythm-control therapy by anti arrhythmic drug and/or catheter ablation in the contemporary clinical practice was associated with the lower incidence of the composite of cardiac death and HF hospitalization, as compared with rate-control therapy in a Japanese AF cohort. However, given the fundamental differences in baseline clinical characteristics between the rhythm- and Rate-control groups, the results cannot be generalizable. PMID- 29797058 TI - Prognostic value of age adjusted segment involvement score as measured by coronary computed tomography: a potential marker of vascular age. AB - Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 +/- 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26 0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification. PMID- 29797061 TI - Split cord malformation type 1 with two hemicord lesions. AB - Split cord malformations are rare entities which may present in an occult manner or in association with other lesions or congenital anomalies. Rarely, these cases may have associated hemicord lesions. We report an unusual case, the first of its kind, a type 1 split cord malformation with two pathologically different lesions (lipoma and dermoid) on one hemicord. PMID- 29797060 TI - Correlates and predictors of paediatric leg pain: a case-control study. AB - Paediatric leg pains, long described as 'growing pains', frequently present to clinicians, are prevalent in early childhood, disrupt sleep, and distress affected children and parents. There are many cited associations, but no defined leg pain sub-types, nor revealed predictive factors. We explored the implicated factors (viz. foot arches, foot strength, joint mobility, vitamin D, iron) in children with leg pain versus a control group. Leg pain sub-groups-growing pains (GP), restless legs (RLS), both (mixed)-are defined for the first time. A case controlled study design, in a primary care setting, Mumbai, India. A total of 77 children with leg pains (n = 64) and controls (n = 13), aged 3-12 years, identified by paediatricians, completed data collection. Blood assays for iron and vitamin D, pain, Beighton score, foot arch, foot strength and anthropometrical data were collected. All outcome measures were validated, with standardised protocols. Leg pain (all groups) was predicted by increased joint mobility and increased ankle dorsiflexion strength (beta = 0.56, P < 0.05). GP sub-group was predicted by increased ankle dorsiflexion strength (beta = - 0.06, P < 0.05). Mixed (GP/RLS) and RLS sub-groups were predicted by increased ankle dorsiflexion strength (beta = 0.66, P < 0.05) and pain questionnaire (beta = 0.11, P < 0.05). Hypovitaminosis D was detected in 87% of the sample, and anaemia in 13%. Increased strength of ankle dorsiflexors and joint flexibility were each found predictive for leg pain. Increased body weight, waist girth, and BMI were all associated with leg pain. PMID- 29797064 TI - DBS in pediatric patients: institutional experience. AB - INTRODUCTION: DBS is initially used for treatment of essential tremor and Parkinson's disease in adults. In 1996, a child with severe life-threatening dystonia was offered DBS to the internal globus pallidus (GPi) with lasting efficacy at 20 years. Since that time, increasing number of children benefited from DBS. PATIENTS AND METHODS: We retrospectively evaluated our database of patients who underwent DBS from 2011 to 2017. All patients <= 17 years of age at the time of implantation of DBS were included in this series. Subjective Benefit Rating Scale (SBRS), Hoehn Yahr Scale (HYS), Fahn Marsden Rating Scale (FMRS), Clinical Global Impressions Scales (CGI), and Yale Global Tic Severity Scale (YGT) were used to evaluate clinical outcome. RESULTS: Between May 2014 and October 2017, 11 children underwent DBS procedure in our institution. Six of them were female and five of them were male. Mean age at surgery was 11.8 +/- 4.06 years (range 5-17 years). In our series, four patients had primary dystonia (PDY) (36.3%), three patients had secondary dystonia (SDY) (27.2%), two patients had JP (18.1%), and two patients had Tourette Syndrome (TS) (18.1%). Two JP patients underwent bilateral STN DBS while the other nine patients underwent bilateral GPi DBS. SBRS scores were 1.75 +/- 0.5 for patients with PDY, 3 +/- 0 for patients with JP, 2.5 +/- 0.7 for patients with TS, and 2 +/- 1 for patients with SDY. Mean FMRS reduction rate was 40.5 for patients with dystonia. Significant improvement was also defined in patients with TS and JP after DBS. None of the patients experienced any intracerebral hemorrhage or other serious adverse neurological effect related to the DBS. Wound complications occurred in two patients. CONCLUSION: There are many literatures that support DBS as a treatment option for pediatric patients with medically refractory neurological disorders. DBS has replaced ablative procedures as a treatment of choice not only for adult patients, but also for pediatric patients. Wound-related complications still remain the most common problem in pediatric patients. Development of smaller and more flexible hardware will improve quality of children's life and minimize wound related complications in the future. PMID- 29797063 TI - Mechanical relationship of filum terminale externum and filum terminale internum: is it possible to detether the spinal cord extradurally? AB - INTRODUCTION: Intradural transection of the filum terminale (FTI) is often used to treat tethered cord syndrome. Recently, some have proposed that the extradural part of the filum terminale (FTE) can be sectioned with equal results but with fewer complications. Therefore, the present cadaveric study aimed to evaluate the anatomical foundation of such procedures. METHODS: A posterior lumbosacral approach was performed on five fresh-frozen cadaveric specimens to expose both the FTI and FTE. Tension was then applied to the FTE and observations and measurements made of any movement of the FTI. Other morphological measurements (e.g., length, diameter) of the FTI and FTE were also made. RESULTS: Although very minimal movement of the FTI was seen in the majority of specimens following tension on the FTE, no specimen was found to have more cranial movement of the conus medullaris or cauda equina. The mean length and diameter of the FTI was 52.2 and 0.38 mm, respectively. The mean length and diameter of the FTE was 77 and 0.60 mm, respectively. The force necessary to move the FTI with tension applied to the FTE had a mean of 0.03 N. The average distance that the FTI moved with distal FTE tension was 1.33 mm. All specimens had a thecal sac that terminated at the S2 vertebral level. And no specimen had a low-lying conus medullaris, cutaneous stigmata of occult spinal dysraphism, or grossly visible adipose tissue in either the FTI or FTE. CONCLUSIONS: Based on our studies, tension placed on the FTE has very little effect on the FTI and no obvious effect on the conus medullaris or cauda equina. Therefore, isolated transection of the FTE for a patient with tethered cord syndrome is unlikely to have significant effect. To our knowledge, this is the first study to quantitate the distal forces needed on the FTE to move the FTI. PMID- 29797066 TI - Intracerebral juvenile xanthogranuloma: an infrequent involvement of hystiocitosis in children. PMID- 29797065 TI - Pediatric intramedullary spinal cord tumor outcomes using the WeeFIM scale. AB - PURPOSE: The Functional Independence Measure for children (WeeFIM) is a user friendly functional outcomes tool that has been validated across other traditional functional scales. Historically, the significant neurologic and functional deficits of intramedullary spinal cord tumors (IMSCTs) have been monitored by coarse or overbearing functional outcomes tools that make it difficult to measure the slow improvement/decline seen in these patients. This study is the first to report WeeFIM outcomes on a series of IMSCTs with emphasis on an aggressive surgical strategy. METHODS: A retrospective review from 2005 to 2014 was performed for nine patients who underwent resective surgery for intramedullary spinal cord tumors with intraoperative ultrasound and neurophysiologic monitoring. WeeFIM scales were assessed at admission and discharge to evaluate changes in severity of disability and need for assistance. RESULTS: At the time of this submission, 7/9 patients are alive. The mean WeeFIM improvement was 27 points (8-50 points) with a mean WeeFIM efficiency of 2.0 points/day. CONCLUSIONS: The WeeFIM scale is an appropriate and useful scale for measuring postoperative improvements in patients with IMSCTs undergoing aggressive resective surgery. Attention to intraoperative spinal cord monitoring and prevention of spinal column instability may prevent morbidity related to surgery, and functional outcomes do not appear to be compromised by an aggressive surgical approach. PMID- 29797062 TI - When and why is surgical revascularization indicated for the treatment of moyamoya syndrome in patients with RASopathies? A systematic review of the literature and a single institute experience. AB - BACKGROUND: Moyamoya disease (MMD) is a cerebrovascular disorder characterized by the progressive occlusion of the supraclinoid internal carotid artery (ICA), resulting in the formation of an abnormal cerebral vascular network. When MMD occurs in association with an underlying medical condition, including some distinctive genetic disorders, it is named moyamoya syndrome (MMS). The discrimination between MMD and MMS has been validated by recent genetic researches and international reviews. Similarly to patients suffering from MMD, patients with MMS generally become symptomatic because of ischemic complications, which lead to hemiparesis, transient ischemic events, seizures, and sensory symptoms. RASopathies are a group of neurodevelopmental disorders that can be associated with MMS. RESULTS: We retrospectively reviewed 18 RASopathy patients with MMS treated at our institution from 2000 to 2015 (16 neurofibromatosis type 1, 1 Costello syndrome, and 1 Schimmelpenning syndrome). Here, we report clinical data, performed surgical procedures, and clinic-radiological outcome of these patients. Most of them received both indirect revascularization and medical therapy. CONCLUSIONS: At the moment, there are no univocal recommendations on which of these two treatment strategies is the treatment of choice in patients with RASopathies and MMS. We suggest that patients with a good overall prognosis (primarily depending on the distinctive underlying genetic disorder) and initial cerebrovascular disease could benefit from a prophylactic surgical revascularization, in order to prevent the cognitive impairment due to the progression of the vasculopathy. PMID- 29797067 TI - Kv7 channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons. AB - Kv7 channels determine the resting membrane potential of neurons and regulate their excitability. Even though dysfunction of Kv7 channels has been linked to several debilitating childhood neuronal disorders, the ontogeny of the constituent genes, which encode Kv7 channels (KNCQ), and expression of their subunits have been largely unexplored. Here, we show that developmentally regulated expression of specific KCNQ mRNA and Kv7 channel subunits in mouse and human striatum is crucial to the functional maturation of mouse striatal neurons and human-induced pluripotent stem cell-derived neurons. This demonstrates their pivotal role in normal development and maturation, the knowledge of which can now be harnessed to synchronise and accelerate neuronal differentiation of stem cell derived neurons, enhancing their utility for disease modelling and drug discovery. PMID- 29797068 TI - Minimal Risk of Biliary Tract Complications, Including Hepatic Abscess, After Transarterial Embolization for Hepatocellular Carcinoma Using Concentrated Antibiotics Mixed with Particles. AB - PURPOSE: To assess the incidence of biliary complications, cholecystitis, and abscess formation in HCC patients following transarterial embolization (TAE) using particles mixed with concentrated antibiotics. MATERIALS AND METHODS: Retrospective review of HCC patients treated with embolization over a 10-year period revealed 499 procedures in 257 patients. TAE was performed with particles mixed with concentrated antibiotics in addition to IV antibiotics. All follow-up imaging after treatment was retrospectively reviewed for the development of bilomas, biliary strictures, acute cholecystitis, and hepatic abscess. Clinical notes and laboratory tests were also reviewed. RESULTS: Mean follow-up duration was 18.2 months. In total, there was one biliary complication consisting of biloma formation. This patient had subsegmental hepatic infarction identified on imaging 8 days post-embolization in the setting of subsegmental portal vein thrombus, with subsequent biloma development. There were no cases of new biliary strictures in the embolized portion of the liver at any point after treatment. One patient developed acute gangrenous cholecystitis 10 days post-procedure. No patients developed a hepatic abscess, although 10 patients had bilioenteric anastomoses or incompetent sphincters of Oddi. CONCLUSIONS: Biliary complications and cholecystitis occurred extremely rarely after TAE, at a markedly lower rate than historical data on TACE. Despite significant risk factors for abscess formation in 10 patients, TAE with particles mixed with concentrated antibiotics resulted in zero abscesses, in contrast to a very high rate after TACE in the literature. PMID- 29797070 TI - Sedation with Propofol for Bronchoscopy in Cystic Fibrosis Lung Transplant Recipients. AB - INTRODUCTION: Flexible fiberoptic bronchoscopy (FFB) plays an important role in the surveillance of cystic fibrosis (CF) patients after lung transplantation (LTx). With rapid onset and clearance, propofol provides a safe and efficient method for sedation during FFB, yet sedation requirements for CF patients are not well described. OBJECTIVES: Due to pharmacokinetic differences for other classes of drugs in CF patients, this study was performed to examine propofol requirements for sedation during bronchoscopy in lung transplant recipients with CF. METHODS: A single-center retrospective cohort study was performed to examine propofol sedation requirements during outpatient surveillance. FFB procedures with transbronchial biopsy (TBB) in post-LTx recipients between 2009 and 2014 were conducted. RESULTS: A total of 40 FFB procedures with TBB were performed 20 CF (11 females), 20 non-CF (11 females). Mean (+/- SD) age was 25.6 +/- 9.2 (range 13-42) years and 22.2 +/- 10.8 (range 11-39) years for the CF and non-CF groups, respectively. Propofol requirements were significantly higher in the CF patients compared to the non-CF patients. Mean (+/- SD) propofol dose for CF patients was 334 +/- 86 versus 214 +/- 88 mg for non-CF patients (p < 0.001). Mean (+/- SD) propofol dose per weight (mg/kg) was 6.5 +/- 2.1 for CF patients versus 3.8 +/- 1.6 for non-CF patients (p < 0.001). CONCLUSIONS: Compared to a non-CF cohort, CF lung transplant recipients required higher dosages of propofol for sedation during FFB with TBB. PMID- 29797072 TI - [Telematics services and telemedicine under ophthalmological legal aspects]. AB - Telemedical solutions are increasing with respect to diversity, frequency and scope. It should be part of medical practice to remind again and again that telemedicine does not represent a special medical field or even a subspecialty. The concept of telemedicine is more used as a superior term for different medical care concepts, provided across distance and time barriers. Telematic solutions implemented as a new field of service in ophthalmological practice or in hospitals must fulfill the following obligatory requirements in conformity with the law: patients must be informed about the range of telemedical solutions, operators must ensure medical specialist qualifications and all care responsibilities combined with the telemedical services must be guaranteed. The legal assessment standard is always the direct comparison between telemedical measures and the individual patient result of medical treatment in a face to face situation in an ophthalmologists practice as the gold standard. The court makes a targeted examination on whether the individual damage to health of a patient under telemedical care would also have normally occurred under medical treatment within the framework of regular care by a medical specialist in a practice or clinic. If the court has a well-founded doubt, the operator must be able to justify either constraints in individual cases or a better prognosis and success rate (reversal of burden of proof). Especially due to the latter aspect it is important for the operator that the standards for telemedical services of the specific medical fields are predefined by the specialist societies or that corresponding results from healthcare research projects are available. PMID- 29797069 TI - Increased Airway Wall Thickness is Associated with Adverse Longitudinal First Second Forced Expiratory Volume Trajectories of Former World Trade Center workers. AB - RATIONALE: Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of a quantitative computed tomography (QCT) imaging measurement of airway wall thickness, and other risk factors for adverse progression. METHODS: We examined the trajectories of expiratory air flow decline in a group of 799 former WTC workers and volunteers with QCT-measured (with two independent systems) wall area percent (WAP) and at least 3 periodic spirometries. We calculated individual regression lines for first-second forced expiratory volume (FEV1), identified subjects with rapidly declining and increasing ("gainers"), and compared them to subjects with normal and "stable" FEV1 decline. We used multivariate logistic regression to model decliner vs. stable trajectories. RESULTS: The mean longitudinal FEV1slopes for the entire study population, and its stable, decliner, and gainer subgroups were, respectively, - 35.8, - 8, - 157.6, and + 173.62 ml/year. WAP was associated with "decliner" status (ORadj 1.08, 95% CI 1.02, 1.14, per 5% increment) compared to stable. Age, weight gain, baseline FEV1 percent predicted, bronchodilator response, and pre-WTC occupational exposures were also significantly associated with accelerated FEV1 decline. Analyses of gainers vs. stable subgroup showed WAP as a significant predictor in unadjusted but not consistently in adjusted analyses. CONCLUSIONS: The apparent normal age related rate of FEV1 decline results from averaging widely divergent trajectories. WAP is significantly associated with accelerated air flow decline in WTC workers. PMID- 29797073 TI - [A young patient with full visual acuity, small visual field defects, and normal fluorescence angiogram]. AB - A 28-year-old female patient came to our clinic complaining of small central visual field defects in both eyes, without any impairments of visual acuity. She reported recent flu-like symptoms and work-related stress associated with high caffeine intake. Dark reddish cloverleaf-shaped lesions were noted in the macular region with red-free fundoscopy, and alterations of the external retinal layers were observed in spectral domain optical coherence tomography (SD-OCT). The visual field test (Octopus, program 32) revealed small central scotoma on both eyes. The fluorescein angiograms were normal. A suspected diagnosis of acute macular neuroretinopathy (AMNR) was made and the patient was scheduled for follow up 4 weeks later. The follow-up examination showed persisting central scotoma as well as persistence of the lesions in the external retinal layers in OCT. The best-corrected visual acuity was still 20/20. In OCT angiography (OCT-A), a reduced correlation signal and therefore perfusion was detected in the outer retinal capillary plexus within the area of the fundoscopic macular lesions. Multimodal imaging, including SD-OCT and A-OCT, plays a pivotal role in the diagnosis of acute macular neuroretinopathy. Even though no serious impairments of visual acuity are reported, patients should be informed about the possibility of permanent central scotoma. PMID- 29797071 TI - Phenotypes of COPD in an Austrian population : National data from the POPE study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a major global health problem; however, there are no data regarding clinical phenotypes of these patients in Austria. METHODS: This was an analysis from the Austrian cohort of the cross-sectional Phenotypes of COPD in Central and Eastern Europe (POPE) study, which was offered to patients with stable COPD in a real-life setting. Patients were recruited at 5 different outpatient facilities in 3 different provinces in Austria. All consecutive patients aged >=40 years with a diagnosis of COPD confirmed by a post-bronchodilator forced expired volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 during a stable state (>=4 weeks without exacerbation or worsening of any relevant comorbidities) were considered eligible. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analyses of differences in patient characteristics, symptom load, comorbidities, and pharmacological treatment. RESULTS: Among 283 patients fulfilling the inclusion criteria, 49.5% were considered non-exacerbators, 21.6% were classified as exacerbators with chronic bronchitis, 21.2% exacerbators without chronic bronchitis, and 7.8% were patients with an asthma-COPD overlap. Exacerbators had significantly higher prevalence of symptoms, lower lung function and exercise capacity, and a higher prevalence of comorbidities, such as heart failure and depression, compared with the other patient phenotypes. A large majority of patients with stable COPD in this cohort received inhaled triple therapy, irrespective of exacerbation history. CONCLUSIONS: There were significant differences in COPD outcome measures between predefined phenotypes of COPD in this study. The majority of patients with stable COPD in this Austrian population were not treated according to current COPD guidelines. While non-exacerbators appear to have been overtreated, patients with an asthma-COPD overlap appear to have been undertreated. PMID- 29797074 TI - Complicated primary cesarean delivery increases the risk for uterine rupture at subsequent trial of labor after cesarean. AB - PURPOSE: To evaluate whether cesarean delivery (CD) indication, labor status, and other primary CD characteristics affect the risk for uterine rupture in subsequent deliveries. METHODS: A case-control study of women attempting trial of labor after cesarean (TOLAC) in a single, tertiary, university-affiliated medical center (2007-2016). Deliveries complicated by uterine rupture were matched to successful vaginal birth after cesarean (VBAC) deliveries in a 1:3 ratio. Indication, labor status and post-partum complications (postpartum hemorrhage and postpartum infection) at primary CD were compared between study and control group. RESULTS: During study period, there were 75,682 deliveries, of them, 3937 (5.2%) were TOLAC. Study group included 53 cases of uterine rupture at TOLAC and 159 women with successful VBAC. Women in study group had significantly lower rates of previous VBAC (15.1 vs. 28.9%, p = 0.047). Rate of postpartum complications at primary CD was significantly higher in women with TOLAC complicated by uterine rupture (7.5 vs. 1.9%, respectively, p = 0.042). Utilizing the multivariate logistic regression analysis, postpartum complications remained an independent risk factor for uterine rupture in the following TOLAC (aOR 4.07, 95% CI 1.14-14.58, p = 0.031). CONCLUSION: Postpartum hemorrhage and infection, in primary CD, seem to be associated with increased risk for uterine rupture during subsequent TOLAC. PMID- 29797075 TI - Prospective cohort study of pregnancy complications and birth outcomes in women with asthma. AB - BACKGROUND: Asthma is the most common potentially serious medical complication in pregnancy. The purpose of this study was to determine the association between maternal asthma and a spectrum of adverse neonatal and maternal outcomes. METHODS: Events during pregnancy and birth outcome were evaluated in 34 asthmatic as well as 1569 non-asthmatic pregnant women who were enrolled in a prospective cohort study undertaken at the antenatal clinics of Mobini Hospital in Iran. The women were interviewed and classified according to clinical severity and asthma control as per GINA guidelines. Information on asthma symptoms was collected by a questionnaire as well as by spirometry and physical examination. All subjects were followed until delivery, and postpartum charts were reviewed to assess neonatal and maternal outcomes. Eosinophil cells counts were obtained and total IgE was measured by ELISA. Results were assessed by multivariate logistic regression adjusting for maternal age and parity, and for birth outcomes, for gestational diabetes, and hypertension/pre-eclampsia. RESULTS: The well-known relationship between family history of asthma and asthma in pregnancy was again supported (p < 0.001). Women with asthma had more bleeding events 3 weeks or more before delivery (OR 3.30, 95% CI 1.41-7.26), more often placenta problems (OR 6.86, 95% CI 1.42-33.02), and gestational diabetes mellitus (OR 3.82, 95% CI 1.06 13.75). No significant differences between asthmatic and non-asthmatic mothers regarding duration of gestation, birthweight, low Apgar scores, or neonatal respiratory difficulties were found. Total IgE antibody levels and eosinophil counts did not differ by asthma control and severity. CONCLUSIONS: Asthma in pregnancy poses some risk for pregnancy complications and adverse perinatal outcomes. Managing asthma effectively throughout pregnancy could benefit women and their babies and help to reduce the health burden associated with asthma during pregnancy. PMID- 29797077 TI - Predator and parasitoid insects along elevational gradients: role of temperature and habitat diversity. AB - Elevational gradients are characterized by strong abiotic variation within small geographical distances and provide a powerful tool to evaluate community response to variation in climatic and other environmental factors. We explored how temperature and habitat diversity shape the diversity of holometabolous predator and parasitoid insects along temperate elevational gradients in the European Alps. We surveyed insect communities along 12 elevational transects that were selected to separate effects of temperature from those of habitat diversity. Pitfall traps and pan traps were placed every 100 m of elevation increment along the transects ranging from 120 to 2200 m a.s.l. Sampling took place once a month from June to September 2015. Four groups characterized by having at least one life stage behaving as predator or parasitoid were examined: tachinids (Diptera), hoverflies (Diptera), sphecids (Hymenoptera) and ground beetles (Coleoptera). Species richness and evenness changed with elevation, but the shape and direction of the elevation-diversity patterns varied between groups. The effect of temperature on species richness was positive for all groups except for hoverflies. Habitat diversity did not affect species richness, while it modulated the evenness of most groups. Often, elevational patterns of species richness and evenness were contrasting. Our study indicates that natural enemies characterized by diverse ecological requirements can be differentially affected by temperature and habitat diversity across the same elevational gradients. As climate warming is predicted to increase mean annual temperatures and exacerbate weather variability, it is also expected to strongly influence natural enemies and their ability to regulate herbivore populations. PMID- 29797076 TI - Clinical and Psychosocial Factors Influencing Retinal Screening Uptake Among Young Adults with Type 2 Diabetes. AB - PURPOSE OF REVIEW: Young adults with type 2 diabetes (T2D, 18-39 years) experience early-onset and rapid progression of diabetic retinopathy (DR), the leading cause of vision loss for working age adults. Despite this, uptake of retinal screening, the crucial first step in preventing vision loss from DR, is low. The aim of this review is to summarize the clinical and psychosocial factors affecting uptake of retinal screening. RECENT FINDINGS: Barriers include lack of diabetes-related symptoms, low personal DR risk perception, high rates of depression and diabetes-related distress, fatalism about inevitability of complications, time and financial constraints, disengagement with existing diabetes self-management services, and perceived stigma due to having a condition associated with older adults. Young adults with T2D are an under-researched population who face an accumulation of barriers to retinal screening. Tailored interventions that address the needs, characteristics, and priorities of young adults with T2D are warranted. PMID- 29797078 TI - Spatiotemporal analysis of the effect of climate change on vegetation health in the Drakensberg Mountain Region of South Africa. AB - The impact of climate change on mountain ecosystems has been in the spotlight for the past three decades. Climate change is generally considered to be a threat to ecosystem health in mountain regions. Vegetation indices can be used to detect shifts in ecosystem phenology and climate change in mountain regions while satellite imagery can play an important role in this process. However, what has remained problematic is determining the extent to which ecosystem phenology is affected by climate change under increasingly warming conditions. In this paper, we use climate and vegetation indices that were derived from satellite data to investigate the link between ecosystem phenology and climate change in the Namahadi Catchment Area of the Drakensberg Mountain Region of South Africa. The time series for climate indices as well as those for gridded precipitation and temperature data were analyzed in order to determine climate shifts, and concomitant changes in vegetation health were assessed in the resultant epochs using vegetation indices. The results indicate that vegetation indices should only be used to assess trends in climate change under relatively pristine conditions, where human influence is limited. This knowledge is important for designing climate change monitoring strategies that are based on ecosystem phenology and vegetation health. PMID- 29797079 TI - Nasal vestibulitis: an under-recognized and under-treated side effect of cancer treatment? AB - PURPOSE: To evaluate the frequency of nasal symptoms termed nasal vestibulitis, including nasal dryness, crusting, bleeding, and pain, among patients receiving systemic, antineoplastic therapy. METHODS: Patients undergoing systemic antineoplastic therapy were interviewed regarding the presence of nasal symptoms. In an explorative approach, Fisher's exact tests were used to identify groups in which frequencies of nasal symptoms were higher than the comparator arm. To account for potential confounding factors, including demographic variables and concurrent therapies, logistic regression analyses were performed, and estimated proportions with their standard errors (SEs) and odds ratios (ORs) were reported. RESULTS: Forty-one percent of the 100 surveyed patients had nasal symptoms, including dryness, pain, bleeding, and scabbing. Higher frequencies were reported among those who had received taxanes (71%) and VEGF-related therapies (78%). For the patients who had received taxanes, after controlling for other factors, the odds of experiencing nasal symptoms were 4.86 times higher than those for patients who did not receive taxanes (90% CI 2.01, 11.76). For patients who received VEGF-related therapies, after controlling for other factors and exposure to taxanes, the odds of experiencing nasal symptoms were 7.38 (90% CI 1.68, 32.51) times higher than those for patients who did not. Sixty-one percent of patients with symptoms said they reported them to their provider, but only 41% of chart notes contained documentation of such; 49% of patients reported treating their symptoms. CONCLUSIONS: Nasal vestibulitis is common among patients receiving taxane- and VEGF-related therapies; these symptoms are infrequently recorded or treated by healthcare providers. PMID- 29797080 TI - Impact of ferric carboxymaltose on the evolution of hemoglobin and ECOG performance status in iron-deficient patients with solid tumors: a 3-month follow up retrospective study. AB - BACKGROUND: Anemia is often associated with a lower quality of life and less tolerance to treatments in cancer patients. OBJECTIVE: The aims of this retrospective study were to assess the biological (hemoglobin, Hb) and clinical (ECOG index) impact of ferric carboxymaltose (FCM) and to identify predictive factors of response in cancer patients with iron deficiency. METHODS: We included 133 patients with solid tumors who received at least one dose of FCM in 2015. RESULTS: At baseline, most patients had metastatic cancer (70%), were undergoing chemotherapy (82%), suffered from anemia (90%), and 72% had an ECOG 0-1 index. Mean Hb level was statistically higher at M1 (108.3 g/L +/- 13.9), M2 (110.3 g/L +/- 16.1), and M3 (111.7 g/L +/- 12.6) than M0 (99.2 g/L +/- 13.9). Mean ECOG score increased significantly at M1 (1.31 +/- 0.80) and M2 (1.31 +/- 0.87) compared to M0 (1.13 +/- 0.80). Variations of ECOG index between M0 and M1 were independent of levels of Hb and ferritin at inclusion and pretreatment use of transfusion and ESAs. Increase of Hb level was higher in patients with Hb < 100 g/L, ferritinemia < 800 ng/ml, or transfused before inclusion. In multivariate analysis, an ECOG index of 0 was the only predictive factor of an increase of ECOG index and Hb level < 100 g/L and ferritinemia < 800 ng/ml were predictive of an increase in Hb. CONCLUSION: Even though there was no improvement in ECOG index, this study did identify an increase of Hb for patients receiving FCM, indicating its potential benefit in iron-deficient cancer patients. PMID- 29797081 TI - Can we predict the success of a parasite to colonise an invasive host? AB - To understand whether a parasite can exploit a novel invasive host species, we measured reproductive performance (number of eggs per female per day, egg size, development rate and size of new imagoes) of fleas from the Negev desert in Israel (two host generalists, Synosternus cleopatrae and Xenopsylla ramesis, and a host specialist, Parapulex chephrenis) when they exploited either a local murid host (Gerbillus andersoni, Meriones crassus and Acomys cahirinus) or two alien hosts (North American heteromyids, Chaetodipus penicillatus and Dipodomys merriami). We asked whether (1) reproductive performance of a flea differs between an alien and a characteristic hosts and (2) this difference is greater in a host specialist than in host generalists. The three fleas performed poorly on alien hosts as compared to local hosts, but the pattern of performance differed both among fleas and within fleas between alien hosts. The response to alien hosts did not depend on the degree of host specificity of a flea. We conclude that successful parasite colonisation of an invasive host is determined by some physiological, immunological and/or behavioural compatibility between a host and a parasite. This compatibility is unique for each host-parasite association, so that the success of a parasite to colonise an invasive host is unpredictable. PMID- 29797082 TI - The course of experimental giardiasis in Mongolian gerbil. AB - Fifteen Mongolian gerbils were inoculated with 10 * 106 viable trophozoites of Giardia intestinalis. Their faeces were examined daily by flotation method and the number of shed cysts was counted. Two animals (male and female) were euthanised at 4- to 5-day intervals (9, 14, 18 days post-infection (DPI)). The remaining nine gerbils were sacrificed and dissected at the end of the experiment (23 DPI). Their small intestinal tissues were processed for examination using histological sectioning and scanning electron microscopy and their complete blood count (CBC) was examined. The highest number of trophozoites at the total was observed in the duodenum in gerbils sacrificed on 14 DPI. Number of shed cysts was positively correlated with number of trophozoites rinsed from the intestine. Infected gerbils had lower body weight gain in comparison with control group and in three male gerbils; diarrhoea occurred during infection. Cyst shedding was negatively correlated with values of mean corpuscular haemoglobin concentration. Females showed another pattern in cyst shedding than males. This information needs to be taken into account while planning the experiments. PMID- 29797083 TI - The cellulose synthase BcsA plays a role in interactions of Salmonella typhimurium with Acanthamoeba castellanii genotype T4. AB - Pathogenic bacteria share their natural habitat with many other organisms such as animals, plants, insects, parasites and amoeba. Interactions between these organisms influence not only the life style of the host organisms, but also modulate bacterial physiology. Adaptation can include biofilm formation, capsule formation, and production of virulence factors. Although biofilm formation is a dominant mode of bacterial life in environmental settings, its role in host pathogen interactions is not extensively studied. In this work, we investigated the role of molecular pathways involved in rdar biofilm formation in the interaction of Salmonella typhimurium with the Acanthamoeba castellanii genotype T4. Genes coding for the rdar biofilm activator CsgD, the cellulose synthase BcsA, and curli fimbriae subunits CsgBA were deleted from the genome of S. typhimurium. Assessment of interactions of wild-type and mutant strains of S. typhimurium with A. castellanii revealed that deletion of the cellulose synthase BcsA promoted association and uptake by A. castellanii, whereas the interactions with csgD and csgBA mutants were not changed. Our findings suggest that cellulose synthase BcsA inhibits the capabilities of S. typhimurium to associate with and invade into A. castellanii. PMID- 29797084 TI - Conditioned media and organic elicitors underpin the production of potent antiplasmodial metabolites by endophytic fungi from Cameroonian medicinal plants. AB - Plasmodial resistance to artemisinin-based combination therapies emphasizes the need for new drug development to control malaria. This paper describes the antiplasmodial activity of metabolites produced by endophytic fungi of three Cameroonian plants. Ethyl acetate extracts of fungi cultivated on three different media were tested against Plasmodium falciparum chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains using the SYBR green florescence assay. Selected endophytes were further grown in potato dextrose broth supplemented with small organic elicitors and their extracts tested for activity. The effect of elicitors on de novo metabolite synthesis was assessed by reverse-phase HPLC. Activity screening of 81 extracts indicated that Aspergillus niger 58 (IC50 2.25 6.69 MUg/mL, Pf3D7), Fusarium sp. N240 (IC50 1.62-4.38 MUg/mL, Pf3D7), Phomopsis sp. N114 (IC50 0.34-7.26 MUg/mL, Pf3D7), and Xylaria sp. N120 (IC50 2.69-6.77 MUg/mL, Pf3D7) produced potent extracts when grown in all three media. Further culture of these endophytes in potato dextrose broth supplemented with each of the eight small organic elicitors and subsequent extracts screening indicated the extract of Phomopsis sp. N114 grown with 1% 1-butanol to be highly selective and extremely potent (IC50 0.20-0.33 MUg/mL; SI > 666). RPHPLC profiles of extracts of Phomopsis sp. N114 grown with or without 1-butanol showed some peaks of enhanced intensities in the former without any qualitative change in the chromatograms. This study showed the ability of selected endophytes to produce potent and selective antiplasmodial metabolites in varied culture conditions. It also showed how the production of desired metabolites can be enhanced by use of small molecular weight elicitors. PMID- 29797087 TI - CGRP Receptor Biology: Is There More Than One Receptor? AB - Calcitonin gene-related peptide (CGRP) has many reported pharmacological actions. Can a single receptor explain all of these? This chapter outlines the molecular nature of reported CGRP binding proteins and their pharmacology. Consideration of whether CGRP has only one or has more receptors is important because of the key role that this peptide plays in migraine. It is widely thought that the calcitonin receptor-like receptor together with receptor activity-modifying protein 1 (RAMP1) is the only relevant receptor for CGRP. However, some closely related receptors also have high affinity for CGRP and it is still plausible that these play a role in CGRP biology, and in migraine. The calcitonin receptor/RAMP1 complex, which is currently called the AMY1 receptor, seems to be the most likely candidate but more investigation is needed to determine its role. PMID- 29797085 TI - Immunization efficacy of cryopreserved genetically attenuated Plasmodium berghei sporozoites. AB - Malaria is transmitted through the injection of Plasmodium sporozoites into the skin by Anopheles mosquitoes. The parasites first replicate within the liver before infecting red blood cells, which leads to the symptoms of the disease. Experimental immunization with attenuated sporozoites that arrest their development in the liver has been extensively investigated in rodent models and humans. Recent technological advances have included the capacity to cryopreserve sporozoites for injection, which has enabled a series of controlled studies on human infection with sporozoites. Here, we used a cryopreservation protocol to test the efficiency of genetically attenuated cryopreserved sporozoites for immunization of mice in comparison with freshly isolated controls. This showed that cryopreserved sporozoites are highly viable as judged by their capacity to migrate in vitro but show only 20% efficiency in liver infection, which impacts their capacity to generate protection of animals in immunization experiments. PMID- 29797088 TI - The Structure of the CGRP and Related Receptors. AB - The canonical CGRP receptor is a complex between calcitonin receptor-like receptor (CLR), a family B G-protein-coupled receptor (GPCR) and receptor activity-modifying protein 1 (RAMP1). A third protein, receptor component protein (RCP) is needed for coupling to Gs. CGRP can interact with other RAMP-receptor complexes, particularly the AMY1 receptor formed between the calcitonin receptor (CTR) and RAMP1. Crystal structures are available for the binding of CGRP27-37 [D31,P34,F35] to the extracellular domain (ECD) of CLR and RAMP1; these show that extreme C-terminal amide of CGRP interacts with W84 of RAMP1 but the rest of the analogue interacts with CLR. Comparison with the crystal structure of a fragment of the allied peptide adrenomedullin bound to the ECD of CLR/RAMP2 confirms the importance of the interaction of the ligand C-terminus and the RAMP in determining pharmacology specificity, although the RAMPs probably also have allosteric actions. A cryo-electron microscope structure of calcitonin bound to the full-length CTR associated with Gs gives important clues as to the structure of the complete receptor and suggests that the N-terminus of CGRP makes contact with His5.40b, high on TM5 of CLR. However, it is currently not known how the RAMPs interact with the TM bundle of any GPCR. Major challenges remain in understanding how the ECD and TM domains work together to determine ligand specificity, and how G-proteins influence this and the role of RCP. It seems likely that allosteric mechanisms are particularly important as are the dynamics of the receptors. PMID- 29797089 TI - The Mechanism FA-Dependent H+ Transport by UCP1. AB - Uncoupling protein 1 (UCP1) is an integral protein of the inner mitochondrial membrane (IMM) that is expressed specifically in brown and beige fat depots. UCP1 is responsible for the production of heat to control core body temperature, the regulation of fat metabolism, and the energy balance. As an uncoupling protein, UCP1 transports H+ across the IMM in presence of long-chain fatty acids (FA), which makes brown fat mitochondria produce heat at the expense of ATP. However, the exact mechanism of UCP1 action has remained difficult to elucidate, because direct methods for studying currents generated by UCP1 were unavailable. Recently, the patch-clamp technique was successfully applied to brown and beige fat mitochondria to directly study H+ currents across the IMM and characterize UCP1 function. A new model of the UCP1 mechanism was proposed based on the patch clamp analysis. In this model, both FA anions (FA-) and H+ are transport substrates of UCP1, and UCP1 operates as a non-canonical FA-/H+ symporter. Here, we summarize recent findings obtained with the patch-clamp technique that describe how UCP1 can transport not only H+ but also FA-. PMID- 29797086 TI - Management of Non-Diffuse Large B Cell Lymphoma Post-Transplant Lymphoproliferative Disorder. AB - OPINION STATEMENT: Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion. Management of PTLD is dependent upon its subtypes. Early-type and polymorphic PTLD generally respond to reduction of immunosuppression and rituximab monotherapy, whereas monomorphic PTLD often requires additional concurrent or sequential use of chemotherapy. For rare subtypes of PTLD, standard of-care guidelines for de novo lymphomas are recommended. Surgical resection or radiotherapy may be used as adjunctive therapy depending on the extent of disease. Non-chemotherapy options such as adoptive T cell therapy have shown promising efficacy and must be explored further. Despite progress in the last decade, overall survival rates continue to be low in published series. This review highlights the need for prospective randomized trials incorporating novel agents to improve outcomes in PTLD. PMID- 29797090 TI - Native xylose-inducible promoter expands the genetic tools for the biomass degrading, extremely thermophilic bacterium Caldicellulosiruptor bescii. AB - Regulated control of both homologous and heterologous gene expression is essential for precise genetic manipulation and metabolic engineering of target microorganisms. However, there are often no options available for inducible promoters when working with non-model microorganisms. These include extremely thermophilic, cellulolytic bacteria that are of interest for renewable lignocellulosic conversion to biofuels and chemicals. In fact, improvements to the genetic systems in these organisms often cease once transformation is achieved. This present study expands the tools available for genetically engineering Caldicellulosiruptor bescii, the most thermophilic cellulose-degrader known growing up to 90 degrees C on unpretreated plant biomass. A native xylose inducible (P xi ) promoter was utilized to control the expression of the reporter gene (ldh) encoding lactate dehydrogenase. The P xi -ldh construct resulted in a both increased ldh expression (20-fold higher) and lactate dehydrogenase activity (32-fold higher) in the presence of xylose compared to when glucose was used as a substrate. Finally, lactate production during growth of the recombinant C. bescii strain was proportional to the initial xylose concentration, showing that tunable expression of genes is now possible using this xylose-inducible system. This study represents a major step in the use of C. bescii as a potential platform microorganism for biotechnological applications using renewable biomass. PMID- 29797092 TI - Pycnodysostosis: the disease of Henri de Toulouse-Lautrec. AB - Pycnodysostosis or Maroteaux-Lamy syndrome is a genotypic bone disorder, with autosomal recessive inheritance, individualized by Lamy and Maroteaux in 1962. It is characterized by diffuse condensation of the skeleton with thickening of the cortex and narrowing of the medullary cavity. This condensation is reminiscent of the one observed in Albers-Schonberg disease, which differs essentially in dysmorphism of the skull (no closure of fontanelles, gaping sutures, hypoplasia of the lower jaw with open mandibular angle) and extremities (hypoplasia or osteolysis of the phalanges). The patients have a short stature, short hands and feet, and malformed nails. The first scientifically correct diagnosis was made by Dr. G. Sejournet who, under the guidance of his teacher Professor J.-A. Lievre, performed extensive research and diagnosed Henri de Toulouse-Lautrec with achondroplasia-related dwarfism. This article describes pycnodysostosis and reports the life of the painter Henri de Toulouse-Lautrec who died from the disease. PMID- 29797093 TI - Posterior dislocation following revision total knee replacement arthroplasty: a case report and literature analysis. AB - Knee dislocation following total knee replacement arthroplasty is a rare but serious complication. The incidence of dislocation following primary total knee arthroplasty with posterior stabilized implants ranges from 0.15 to 0.5%, and posterior dislocation after revision total knee arthroplasty is even rarer. Here, we report the case of a 76-year-old male who presented with posterior dislocation after posterior stabilized revision total knee arthroplasty. PMID- 29797094 TI - Functional outcomes of the failed plate fixation in distal tibial fractures salvaged by hexapod external fixator. AB - PURPOSE: The purpose of this study was to evaluate the clinical and functional outcomes of failed plate fixation in distal tibia fractures salvaged with hexapod circular fixators. MATERIALS AND METHODS: The database of a specialized limb reconstruction center was searched for all patients with failed plate fixation undergoing limb reconstruction with a circular external fixator between 2008 and 2017. Patients between the ages of 18-65 years, with a symptomatic distal tibia malunion or non-union following plate and screw fixation were included. The SF-12 and Foot Function Index (FFI) scoring systems were used to measure clinical and functional outcomes. RESULTS: Ten patients with a mean age of 38 +/- 13 years met the inclusion criteria. Seven patients had an infected non-union, two hypertrophic non-unions, and one a malunion. The mean follow-up was 41.7 +/- 28.3 months. The mean duration of external fixation was 232.9 +/- 146.6 days. The SF 12 demonstrated a mean score of 49.4 +/- 7.7 for the physical component and a mean score of 55.3 +/- 8.1 for the mental component. Five patients (50%) scored above 45 points for the SF12 physical component, and nine patients (90%) scored above 45 points for the mental component, indicating good outcome can be achieved. The mean FFI score was 24.9 +/- 19.9, and six patients had a score below 14 points (good outcome). Radiological union was observed in all 10 patients at a mean of 29 +/- 14 months. CONCLUSIONS: The results of this study suggest that hexapod circular external fixation is an attractive surgical alternative for the treatment of failed plate fixation of distal tibial fractures, and can reliably achieve bony union and result in very satisfactory clinical outcomes. LEVEL OF EVIDENCE: Level IV case series. PMID- 29797096 TI - Correction to: Antimicrobial-coated sutures to decrease surgical site infections: a systematic review and meta-analysis. AB - In the original version of this article, reference citations found in Tables 2, 3, and 4 contain errors in linking. The correct tables are reproduced below. PMID- 29797091 TI - Molecular and epigenetic regulations and functions of the LAFL transcriptional regulators that control seed development. AB - The LAFL (i.e. LEC1, ABI3, FUS3, and LEC2) master transcriptional regulators interact to form different complexes that induce embryo development and maturation, and inhibit seed germination and vegetative growth in Arabidopsis. Orthologous genes involved in similar regulatory processes have been described in various angiosperms including important crop species. Consistent with a prominent role of the LAFL regulators in triggering and maintaining embryonic cell fate, their expression appears finely tuned in different tissues during seed development and tightly repressed in vegetative tissues by a surprisingly high number of genetic and epigenetic factors. Partial functional redundancies and intricate feedback regulations of the LAFL have hampered the elucidation of the underpinning molecular mechanisms. Nevertheless, genetic, genomic, cellular, molecular, and biochemical analyses implemented during the last years have greatly improved our knowledge of the LALF network. Here we summarize and discuss recent progress, together with current issues required to gain a comprehensive insight into the network, including the emerging function of LEC1 and possibly LEC2 as pioneer transcription factors. PMID- 29797097 TI - Reflex activity of pelvic floor muscles during drop landings and mini trampolining-exploratory study. AB - INTRODUCTION: Complex functional movements such as jumping typically provoke stress urinary incontinence (SUI) in women. The aim of this study was to investigate pelvic floor muscle (PFM) activity in young, healthy women during jumps to explore their activity characteristics. METHODS: Surface electromyography (EMG) from PFMs was measured in 16 healthy women with a tripolar vaginal probe during drop landings from heights of 15, 30 and 45 cm (DL 15, 30, 45) as well as during mini-trampolining with a pace of 90 and 75 jumps per minute (MT 90, 75). Time of foot strike and body weight force (BWF) in % (= ground reaction force, normalised to body weight) was determined by force plates. Root mean square values of the EMG signals were analyzed from 30 ms before to 150 ms after foot strike. Peak activity during maximum voluntary contraction (MVC) was set as 100% for EMG normalization. The PFM onset threshold was determined as the mean of rest activity plus 2 standard deviations. Data were analysed with non parametric statistical methods. RESULTS: EMG activity during all jumps was above the PFM onset threshold. Mean pre- and reflex activity increased significantly with jumping height (p < 0.05) as well as with increasing BWF. The PFM activation pattern of DL was with peak activity of 115-182 %MVC between 34 and 44 ms after foot strike, which was different from MT with peak PFM activity of 85-115 %MVC reached at 133 ms. CONCLUSIONS: Jumping and mini-trampolining provoked significant PFM activity in healthy volunteers. The next research step will be to examine the PFM activity of women suffering from SUI during jumps. PMID- 29797095 TI - Leveraging epigenomics and contactomics data to investigate SNP pairs in GWAS. AB - Although Genome Wide Association Studies (GWAS) have led to many valuable insights into the genetic bases of common diseases over the past decade, the issue of missing heritability has surfaced, as the discovered main effect genetic variants found to date do not account for much of a trait's predicted genetic component. We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. PMID- 29797098 TI - Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications. AB - Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83 100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters. PMID- 29797099 TI - The Use of Sideline Video Review to Facilitate Management Decisions Following Head Trauma in Super Rugby. AB - BACKGROUND: Sideline video review has been increasingly used to evaluate risk of concussive injury during match play of a number of collision sports, with the view to reducing the incidence of match play concussion injuries. The purpose of this study was to evaluate the effectiveness of sideline video review for identifying and evaluating head impact events in Rugby Union. METHODS: All Australian teams' 2015 Super Rugby season matches were studied. Meaningful head impact events (HIEs) were identified, comprising events identified and acted upon during matches and events identified through a post-season retrospective review. Video footage of each HIE was coded by two experienced independent sports medicine clinicians to evaluate management decisions made by match-day (MDD) and team doctors (TD). HIE incidences for matches with and without sideline video were compared, and the agreement between game-day video interpretation and the independent clinician opinion calculated. RESULTS: Seventy HIEs were identified in 83 matches (47 identified during matches and 23 identified post-season), equating to 42.5 HIEs per 1000 player match hours. When video review was available, an unnoticed HIE occurred once every 4.3 matches, compared to once every 2.3 matches when the sideline video review was unavailable. Of the 47 identified in-match HIEs evaluated by TD and MDD during the season, 18 resulted in an immediate and permanent removal, 28 resulted in temporary removal for an off-field assessment, and one resulted in the player continuing the game. Game day head injury assessment process video decisions agreed with the independent clinician view in 72% of cases, kappa = 0.49 (95% CI 0.38-0.59, weak agreement). CONCLUSIONS: These findings suggest that access to sideline video review is an important supplementary component to identify potential concussions; however, there is a critical need for improved systems and processes to reduce the likelihood of missing an incident. PMID- 29797100 TI - Factors associated with acute medication overuse in people with migraine: results from the 2017 migraine in America symptoms and treatment (MAST) study. AB - BACKGROUND: The MAST Study is a longitudinal, cross-sectional survey study of US adults with migraine. These analyses were conducted to estimate rates of acute medication overuse (AMO) and determine associations of AMO with individual and headache characteristics. METHODS: Eligible respondents had ICHD-3-beta migraine, reported >=3 monthly headache days (MHDs) in the past 3 months, >=1 MHD in the past 30 days, and currently took acute headache medication. AMO was defined according to ICHD-3-beta thresholds for monthly days of medication taking when diagnosing medication overuse headache. RESULTS: Eligible respondents (N = 13,649) had a mean age of 43.4 +/- 13.6 years; most were female (72.9%) and Caucasian (81.9%). Altogether, 15.4% of respondents met criteria for AMO. Compared with those not overusing medications, respondents with AMO were significantly more likely to be taking triptans (31.3% vs 14.2%), opioids (23.8% vs 8.0%), barbiturates (7.8% vs 2.7%), and ergot alkaloids (3.1% vs 0.6%) and significantly less likely to be taking NSAIDs (63.3% vs 69.8%) (p < 0.001 for all comparisons). Respondents with AMO had significantly more MHDs (12.9 +/- 8.6 vs 4.3 +/- 4.3, p < 0.001); higher migraine symptom severity (17.8 +/- 2.7 vs 16.4 +/- 3.0, p < 0.001), higher pain intensity scores (7.4 vs 6.5, p < 0.001); and higher rates of cutaneous allodynia (53.7% vs 37.5%, p < 0.001). Adjusted for MHDs, the odds of AMO were increased by each additional year of age (OR 1.02, 95% CI 1.02, 1.03); being married (OR 1.19, 95% CI 1.06, 1.34); smoking (OR 1.54, 95% CI 1.31, 1.81); having psychological symptoms (OR 1.62, 95% CI 1.43, 1.83) or cutaneous allodynia (OR 1.22, 95% CI 1.08, 1.37); and greater migraine symptom severity (OR 1.06, 95% CI 1.04, 1.09) and pain intensity (OR 1.27, 95% CI 1.22, 1.32). Cutaneous allodynia increased the risk of AMO by 61% in males (OR 1.61, 95% CI 1.28, 2.03) but did not increase risk in females (OR 1.08, 95% CI 0.94, 1.25). CONCLUSIONS: AMO was present in 15% of respondents with migraine. AMO was associated with higher symptom severity scores, pain intensity, and rates of cutaneous allodynia. AMO was more likely in triptan, opioid, and barbiturate users but less likely in NSAID users. Cutaneous allodynia was associated with AMO in men but not women. This gender difference merits additional exploration. PMID- 29797102 TI - Interleukin-10 and collagen type II immunoexpression are modulated by photobiomodulation associated to aerobic and aquatic exercises in an experimental model of osteoarthritis. AB - The aim of this study was to compare the effects of photobiomodulation (PBM) associated with an aerobic and an aquatic exercise training on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Fifty male Wistar rats were randomly divided into 5 groups: OA control group (CG), OA plus aerobic training group (AET), OA plus aquatic training group (AQT), OA plus aerobic training associated with PBM group (AETL), OA plus aquatic training associated with PBM group (AQTL). The aerobic training (treadmill; 16 m/min; 50 min/day) and the aquatic training (water jumping; 50-80% of their body mass) started 4 weeks after the surgery and they were performed 3 days/week for 8 weeks. Moreover, PBM was performed after the physical exercise trainings on the left joint. Morphological characteristics and immunoexpression of IL-10, TGF beta, and collagen type I (Col I) and II (Col II) of the articular cartilage were evaluated. The results showed that all the treated groups (exercise and PBM) presented less intense signs of degradation (measured by histopathological analysis and OARSI grade system). Additionally, aerobic and aquatic exercise training rats (associated or not with PBM) showed increased IL-10 (AET p = 0.0452; AETL p = 0.03; AQTL p = 0.0193) and Col II (AET p = 0.012; AQT p = 0.0437; AETL p = 0.0001; AQTL p = 0.0001) protein expression compared to CG. Furthermore, a statistically higher TGF-beta expression was observed in AET (p = 0.0084) and AETL (p = 0.0076) compared to CG. These results suggest that PBM associated with aerobic and aquatic exercise training were effective in mediating chondroprotective effects and maintaining the integrity of the articular tissue in the knees of OA rats. PMID- 29797101 TI - Considerations for the Use of Polysorbates in Biopharmaceuticals. AB - PURPOSE: Polysorbates are commonly added to protein formulations and serve an important function as stabilizers. This paper reviews recent literature detailing some of the issues seen with the use of polysorbate 80 and polysorbate 20 in protein formulations. Based on this knowledge, a development strategy is proposed that leads to a control strategy for polysorbates in protein formulations. METHODS: A consortium of Biopharmaceutical scientists working in the area of protein formulations, shared experiences with polysorbates as stabilizers in their formulations. RESULTS: Based on the authors experiences and recent published literature, a recommendation is put forth for a development strategy which will lead into the appropriate control strategy for these excipients. CONCLUSIONS: An appropriate control strategy may comprise one or more elements of raw material, in-process and manufacturing controls. Additionally, understanding the role, if any, polysorbates play during stability will require knowledge of the criticality of the excipient, based upon its impact on CQAs due to variations in concentration and degradation level. PMID- 29797103 TI - Limited English Proficiency and Health Service Use in Asian Americans. AB - The present study examined the extent to which limited English proficiency (LEP) poses a risk to health service use in Asian Americans. With data drawn from the 2015 Asian American Quality of Life Survey (N = 2594), logistic regression was used to model the odds for four outcomes (no usual place for care, no regular check-up, unmet needs for medical care, and communication problems in healthcare settings). More than 62% of the sample had LEP. In the group with LEP, the odds of not having usual place for care increased by 2.09 times, of not having regular check-up by 1.69 times, of having unmet needs for medical care by 1.89 times, and of having communication problems in healthcare settings by 4.95 times. The findings highlight the vulnerabilities of Asian Americans with LEP in health service use and provide implications for health planning and interventions. PMID- 29797105 TI - Feasibility study of advanced focused cardiac measurements within the emergency department. AB - BACKGROUND: This study aims to compare the increased time needed to perform advanced focused cardiac measurements in the emergency department, including diastolic heart failure evaluation via E/E', and cardiac output with LVOT/VTI. Patients with pertinent cardiopulmonary symptoms in the emergency department had a focused cardiac ultrasound performed by the emergency department ultrasound team. The ability to obtain basic cardiac windows, evaluate for effusion, systolic ejection fraction, and right-sided heart pressures were recorded. Advanced measurements, along with time to obtain all images and the training level of the provider, were recorded. RESULTS: Fifty-three patients were enrolled. Basic focused cardiac windows were able to be obtained in 80% of patients. The average 4-window focused cardiac ultrasound took 4 min and 49 s to perform. Diastolic measurements were able to be obtained in 51% of patients, taking an average of 3 min and 17 s. Cardiac output measurements were able to be obtained in 53% of patients, taking an average of 3 min and 8 s. CONCLUSION: The ability to obtain these images improved with increasing level of training. Performing both cardiac output and diastolic measurements increased the time with bedside ultrasound by 6 min and 25 s, and were able to be obtained in slightly over half of all ED patients. PMID- 29797106 TI - A nationwide survey of undergraduate training in oral and maxillofacial surgery. AB - PURPOSE: To investigate the current status of undergraduate training in oral and maxillofacial (OMF) surgery in Germany using a nationwide survey and hence contribute to an educational improvement in the field. METHODS: A 39-item questionnaire was sent to all university clinics with an OMF surgery chair in Germany (n = 34). RESULTS: Ninety-two percent of OMF clinics are involved in the curricular training in medicine and 100% in dentistry. Eighty-one percent of OMF clinics perform curricular examinations and, respectively, 86% in dentistry. Examinations are mainly performed written with multiple-choice tests (62% medicine, 76% dentistry) and using non-structured oral examinations (57% medicine, 86% dentistry). Objective structured clinical examinations (OSCEs) are only used in 19% of all faculties. CONCLUSION: OMF surgery with its involvement both in medical and dental education has a special position as a surgical discipline. Our results show that OMF as a specialty is underrepresented in dental and especially in medical education considering the numerical and health economic importance of OMF consultations. Enhancing curricular integration and developing more structured examination forms is necessary to guarantee a high quality of OMF education. PMID- 29797108 TI - "We Raise our Grandchildren as our Own:" Alaska Native Grandparents Raising Grandchildren in Southwest Alaska. AB - This study explores continuity and change in the roles of rural Alaska Native grandparents, describing their importance in contemporary Yup'ik social life and structure. The study is distinctive in its focus on the experiences of Yup'ik grandparents who are primary caregivers raising their grandchildren in Southwest Alaska. Qualitative data were gathered using a semi-structured interview from 20 Yup'ik grandparents, ages 46 to 95, who raised their grandchildren as the primary caregiver for at least one year. Content analysis was used to establish a culturally grounded understanding of the role of a grandparent raising grandchildren and meanings of these roles to Yup'ik grandparents. Findings reveal areas of continuity and change in the role and place of grandparents in Yup'ik families and communities. Important continuities persist in the role of Yup'ik grandparents, who continue to be a vital resource within their families and communities. As in the past, the grandparent role is essential in passing down cultural knowledge, upholding traditional Yup'ik values and teachings, and facilitating development of a strong and healthy cultural identity among youth. However, significant change has taken place within Yup'ik communities as a result of Western colonization. Grandparent roles are also shifting and expanding as a result of these changes, as part of an adaptive community response to ensure the safety and well-being of youth during times of great change and disruption. PMID- 29797107 TI - Use of 3-D printing technologies in craniomaxillofacial surgery: a review. AB - Three-dimensional (3-D) printing is a method of manufacturing in which materials like plastic or metal are deposited onto one another in layers to produce a 3-D object. Because of the complex anatomy of craniomaxillofacial structures, full recovery of craniomaxillofacial tissues from trauma, surgeries, or congenital malformations is extremely challenging. 3-D printing of scaffolds, tissue analogs, and organs has been proposed as an exciting alternative to address some of these key challenges in craniomaxillofacial surgery. There are four broad types of 3-D printing surgical applications that can be used in craniomaxillofacial surgery: contour models (positive-space models to allow preapplication of hardware before surgery), guides (negative-space models of actual patient data to guide cutting and drilling), splints (negative-space models of virtual postoperative positions to guide final alignment), and implants (negative-space 3-D printed implantable materials or 3-D printed molds into which nonprintable materials are poured). 3-D printing technology is being successfully used for surgeries for head and neck malignancies, mandibular reconstruction, orthognathic surgeries, for mandibulectomies after osteoradionecrosis, orbital floor fracture surgeries, nasal reconstruction, and cranioplasties. The excitement behind 3-D printing continues to increase and hopefully will drive improvements in the technology and its surgical applications, especially in craniomaxillofacial region. This present review sets out to explore use of 3-D printing technologies in craniomaxillofacial surgery. PMID- 29797109 TI - Effectiveness and safety of switching from prostaglandin analog monotherapy to prostaglandin/timolol fixed combination therapy or adding ripasudil. AB - PURPOSE: To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy. STUDY DESIGN: An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined. RESULTS: The mean IOP after 3 months of therapy was 14.3 +/- 2.2 mmHg in the switched group and 14.7 +/- 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 +/- 3.0 mmHg; added, 16.6 +/- 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 +/- 1.7 mmHg (11.7 +/- 9.6%) in the switched group and by 1.8 +/- 2.1 mmHg (10.7 +/- 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group. CONCLUSION: Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP. PMID- 29797110 TI - Pigeons play the percentages: computation of probability in a bird. AB - The ability to compute probability, previously shown in nonverbal infants, apes, and monkeys, was examined in three experiments with pigeons. After responding to individually presented keys in an operant chamber that delivered reinforcement with varying probabilities, pigeons chose between these keys on probe trials. Pigeons strongly preferred a 75% reinforced key over a 25% reinforced key, even when the total number of reinforcers obtained on each key was equated. When both keys delivered 50% reinforcement, pigeons showed indifference between them, even though three times more reinforcers were obtained on one key than on the other. It is suggested that computation of probability may be common to many classes of animals and may be driven by the need to forage successfully for nutritional food items, mates, and areas with a low density of predators. PMID- 29797111 TI - EMS providers do not use FOAM for education. AB - BACKGROUND: Free open access to medical education (FOAM, #FOAM) is the free availability of educational materials on various medicine topics. We hope to evaluate the use of social media and FOAM by emergency medical services (EMS) providers. METHODS: We designed an online survey distributed to EMS providers with questions about demographics and social media/FOAM use by providers. The survey was sent to the American College of Emergency Physicians (ACEP) EMS Listserv of medical directors and was asked to be distributed to their respective agencies. The survey was designed to inquire about the providers' knowledge of FOAM and social media and their use of the above for EMS education. RESULTS: There were 169 respondents out of a total of 523 providers yielding a response rate of 32.3%. Fifty-three percent of respondents are paramedics, 37% are EMT Basic trained, and the remainder (16%) were "other." The minority (20%) of respondents had heard of FOAM. However, 54% of respondents had heard of "free medical education online" regarding pertinent topics. Of the total respondents who used social media for education, 31% used Facebook and 23% used blogs and podcasts as resources for online education. Only 4% of respondents stated they produced FOAM content. Seventy-six percent of respondents said they were "interested" or "very interested" in using FOAM for medical education. If FOAM provided continuing medical education (CME), 83% of respondents would be interested in using it. CONCLUSION: Social media is not used frequently by EMS providers for the purposes of FOAM. There is interest within EMS providers to use FOAM for education, even if CME was not provided. FOAM can provide a novel area of education for EMS. PMID- 29797112 TI - Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro immune system: a common path to neurodegenerative diseases? AB - Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features. PMID- 29797113 TI - Region-specific constitutive modeling of the plantar soft tissue. AB - Recent research has shown that hyperelastic properties of the plantar soft tissue consisting of adipose tissue and fibrous septa change from region to region. However, relatively little research has been conducted to develop analytical or computational models to describe the region-specific behavior of the plantar soft tissue. The objective of the research is to develop a region-specific constitutive model of the plantar soft tissue. Plantar soft tissue specimens were dissected from six regions [subcalcaneal (CA), sublateral (LA), subnavicular (Nav), 1st, 3rd, and 5th submetatarsal (M1, M3, M5)] from cadaveric foot samples, and a picrosirius red staining technique was used to visualize the collagen fibers in fibrous septa. The volume fractions of adipose tissue and fibrous septa and the volume fractions of the principal orientations of the fibrous septa were calculated with the intensity gradient method. Region-specific constitutive models were then developed in finite element analysis considering the microstructure of the plantar soft tissue. The hyperelastic region specific material properties of the plantar soft tissue were validated with experimental unconfined compression tests and indentation tests from the literature. The results show that the models give reasonable predictions of the stiffness of the soft tissue within a standard deviation of the tests. The region-specific constitutive models help to explain how changes in the constituents are related to mechanical behavior of the soft tissue on a region specific basis. PMID- 29797115 TI - Long-Term Outcome After Surgery for a Localized Retroperitoneal Soft Tissue Sarcoma in Elderly Patients: Results from a Retrospective, Single-Center Study. AB - BACKGROUND: To evaluate short- and long-term results after curative surgery for a retroperitoneal sarcoma (RPS) in elderly patients. METHODS: We retrospectively analyzed data of all patients operated in our single, tertiary care center for a nonmetastatic RPS and identified patients aged 70 years and older. RESULTS: Among 296 patients with an RPS treated between 1994 and 2015, 60 (20%) were aged 70 years and older (median age 74 years; range 70-85). The median tumor size was 24 cm (range 6-46). Forty-six patients (77%) had mass-related symptoms at the time of diagnosis. The most frequent histological subtypes were de-differentiated liposarcoma (53%, n = 32) and well-differentiated liposarcoma (35%, n = 21). Twenty-two patients (37%) had perioperative radiotherapy and/or chemotherapy. Fifty-eight patients (97%) had macroscopically complete resection. The postoperative mortality was 8% and severe morbidity (Dindo/Clavien >= 3) was 32%. A reoperation was required for ten patients (17%). After a median follow-up of 20 months (range 1-121), the 5-year overall survival (OS) rate was 90% (95% confidence interval [CI] 79-100%), and median OS was not reached. The cancer specific death rate was 88%. No prognostic factor for disease-specific survival was detected. The 5-year disease-free survival (DFS) rate was 52% (95% CI 33-84%) and 5-year locoregional recurrence-free survival rate was 52% (95% CI 33-84%). Median DFS was 94 months (95% CI 35-NA). Reoperation after inappropriate surgery and postoperative morbidity were independent predictive factors of locoregional relapse. No predictive factors of distant metastasis were found. CONCLUSIONS: Curative surgery is feasible in selected elderly patients but with higher mortality and morbidity rates than in younger patients. It enables a prolonged survival. Future studies should focus on selection process to minimize postoperative mortality and morbidity. PMID- 29797104 TI - Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. AB - BACKGROUND: Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis. METHODS: Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID MigraineTM questionnaire, a validated screen used to predict the probability of migraine. RESULTS: Of 2032 patients, 21 illnesses were treated with cannabis. Pain syndromes accounted for 42.4% (n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID MigraineTM questionnaire, with 68% (n = 343) giving 3 "Yes" responses, 20% (n = 102) giving 2 "Yes" responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with "OG Shark" the most preferred strain in the ID MigraineTM and headache groups. Many pain patients substituted prescription medications with cannabis (41.2-59.5%), most commonly opiates/opioids (40.5-72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%). CONCLUSIONS: Chronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID MigraineTM, headache, and most pain groups, with "OG Shark", a high THC (Delta9 tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes beta caryophyllene and beta-myrcene, most preferred in the headache and ID MigraineTM groups. This could reflect the potent analgesic, anti-inflammatory, and anti emetic properties of THC, with anti-inflammatory and analgesic properties of beta caryophyllene and beta-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes. PMID- 29797116 TI - Using invertebrate model organisms for neuroscience research and training: an opportunity for Africa. AB - Africa is faced with an increasing underrepresentation of her research progress in many fields of science including neuroscience. This underrepresentation stems from the very low investments directed towards research by African governments as these are thought to be high-priced. Scientists and researchers within the continent are left to compete highly for the very limited research grants or choose to fund research from their personal purse. Therefore, presenting a need for all possible strategies to make science and research approaches more affordable in Africa. This paper presents one of such strategy, which advocates the use of invertebrate animal models for neuroscience research in place of the commonly used vertebrate models. Invertebrates are cheaper, more available and easy to handle options and their use is on the rise, even in the developed societies of the world. Here, we investigate the current state of invertebrate neuroscience research in Africa looking at countries and institutions conducting neuroscience research with invertebrates and their publication output. We discuss the factors which impede invertebrate neuroscience research in Africa like lack of research infrastructure and adequate expert scientists and conclude by suggesting solutions to these challenges. PMID- 29797117 TI - Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis. AB - The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia >=11.35 MUmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-alpha, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-alpha, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-alpha and TNFR pathways or to CAM. PMID- 29797118 TI - Functional Parameters of Physiological Systems of Laboratory Primates after Administration of Doxorubicin and Transplantation of Mesenchymal Stem Cells. AB - We studied physiological parameters of rhesus monkeys after administration of anthracycline antibiotic doxorubicin. Intravenous administration of the drug caused intoxication manifested in in an abrupt body weight loss, baldness, vomiting, and exicosis. Intoxication in monkeys determined by the damaging effects of doxorubicin on organs and tissues is also characterized by significant changes in the blood: leukopenia, thrombocytopenia, neutropenia, monocytopenia, lymphocytosis, and a sharp drop of CD20+ B cell content. The total protein and albumin content in the blood significantly decreased. A sharp increase in C reactive protein was also accompanied by an increase in activity of proinflammatory cytokine IL-6. Transplantation of mesenchymal stem cells in some cases can significantly alleviate doxorubicin-induced damage to organs and maintain normal clinical status of monkeys after two injections of the drug. Late transplantation of stem cells does not have a protective effect and does not protect the animals from the damaging effects of doxorubicin. We found that the protective effect of mesenchymal stem cells depends on the dose of the drug, total number of cells, and the time of their transplantation. It should be noted that human and monkey mesenchymal stem cells produce similar regenerative effects, at least in the doxorubicin toxicity model. PMID- 29797119 TI - Optical and Electron Microscopic Study of the Morphology and Ultrastructure of Biofilms Formed by Streptococcus pyogenes. AB - Our study confirmed the capacity of S. pyogenes strains to form biofilms on abiotic surfaces. Chains of streptococci surrounded by bluish film were seen under a microscope after alcian blue staining of the preparations grown on slides. On ultrathin sections in transmission electron microscope, the extracellular matrix (indicator of biofilm maturity) became visible after staining with alcian blue. Microscopy of the sections shows structures characteristic of a biofilm in spaces between the cells. Scanning electron microscopy also demonstrates the presence of a biomembrane. Importantly that type 1M strain forming in fact no membranes when cultured on plastic plates (Costar) formed biofilms on the glass. It seems that the conditions for the biofilm formation on the plastic and on the glass differ, due to which the exopolymeric matrices formed on different surfaces vary by biochemical composition. PMID- 29797120 TI - Effect of Coenzyme Q10 on Expression of UbiAd1 Gene in Rat Model of Local Cerebral Ischemia. AB - The study examined the effect of endogenous lipid-soluble antioxidant coenzyme Q10 on the expression of UbiA gene of prenyltransferase domain-containing protein 1 (UbiAd1) involved in synthesis of vitamin K2 (and probably of coenzyme Q10) on a rat model of ischemic stroke provoked by ligation of the middle cerebral artery in the left hemisphere. Ischemia enhanced expression of mRNA of UbiAd1 gene in both cerebral hemispheres, but the effect was significant only in the contralateral one. The study revealed no effect of intraperitoneal injection of coenzyme Q10 (30 mg/kg) on ischemia-produced elevation of mRNA of UbiAd1 gene. Further studies are needed to assess possible neuroprotective effects of antioxidant coenzyme Q10. PMID- 29797121 TI - Expression of Beclin-1 and LAMP-2 in Rat Hippocampus under Conditions of Simulated Gravity Overload in the Caudocranial Vector. AB - Structural changes in the rat hippocampus in response to chronic cerebrovascular disorders induced by gravity exposure in the caudocranial vector were studied. Qualitative and quantitative morphological analysis detected significant cytoarchitectonic changes in the pyramidal layer: spongiosis, manifest pericellular and perivascular edema, and a drastic increase in the counts of pyramidal neurons with signs of impairment in all hippocampal zones. The density of perikarya in the pyramidal layer decreased. Immunohistochemical study detected high expression of Beclin-1 in CA1 field. High expression of LAMP-2 was detected in CA4 field. Field CA2 was characterized by the maximum counts of damaged cells and high expression of Beclin-1 and LAMP-2. PMID- 29797122 TI - IL6R Gene Polymorphic Variant rs2228145(C >A) as a Marker of Genetic Liability to Nonalcoholic Steatohepatitis in the Russian Population of Karelia. AB - Association of IL6R gene polymorphic variant rs2228145(C>A) with the development of nonalcoholic steatohepatitis in Karelia residents is detected. The risk of nonalcoholic steatohepatitis is more than 2-fold higher in carriers of CC genotype by rs2228145 polymorphic marker than in carriers of other genotypes. Plasma levels of IL-6 and the content of IL6R gene transcripts in the peripheral blood leukocytes are higher in patients with nonalcoholic steatohepatitis than in normal subjects. No relationships between rs2228145 polymorphism and the level of IL-6 and content of IL6 and IL6R mRNA were detected. Gene IL6R polymorphic variant rs2228145(C>A) seems to be involved in genetic predisposition of the population of Karelia to nonalcoholic steatohepatitis. However, biochemical and molecular mechanisms underlying the relationship of rs2228145 with the development of nonalcoholic steatohepatitis are not yet studied. PMID- 29797123 TI - Interspecific Differences in Behavioral Responses and Neuromotorics between Laboratory Rodents Receiving Rations with Easily Digested Carbohydrates. AB - We assessed the effect of intake of easily digested carbohydrates for 133 days on quantitative parameters of neuromotorics and cognitive function in Wistar rats and C57Bl/6J mice. Neuromotorics (muscle tone) was assessed in rats and mice by the forelimb muscle force (grip strength) over 4 months. Anxiety was assessed in the elevated plus-maze test and cognitive function (short-term and long-term memory) was evaluated by conditioned passive avoidance response (CPAR) test over 3 months. The mice, in contrast to rats, receiving the diet with easily digested sugars demonstrated suppression of neuromotorics. Anxiety increased with age in female mice, but not in rats, irrespective of the diet. Cognitive function in rats receiving experimental rations did not change significantly in comparison with the control. In mice, consumption of equimolar mixture of fructose and glucose impared short-term, but not long-term memory, in comparison with the group receiving glucose alone. We revealed a small (by 14-17%), but statistically significant increase in the brain weight in mice receiving fructose and sucrose. The study demonstrates sufficient interspecies differences in the influence of carbohydrate rations on neuromotorics and behavioral responses in the in vivo metabolic syndrome model. PMID- 29797124 TI - Mechanisms of Antiviral Activity of the Polyphenol Complex from Seagrass of the Zosteraceae Family against Tick-Borne Encephalitis Virus. AB - Antiviral activity of the polyphenol complex from seagrass of the Zosteraceae family against highly pathogenic strain of the tick-borne encephalitis virus was studied on passaged culture of porcine embryo kidney cells. The antiviral effect of the test compound manifested in a decrease in the infectious titer of the virus and depended on the concentration and application schemes. Polyphenol complex in a concentration of 100 MUg/ml suppressed accumulation of the pathogen in the cell culture: pretreatment of the virus reduced its titer by 4 log, pretreatment of cells by 1.4 log, and application of the compound 1 h after cell infection by 2.8 log. Antiviral action of the test compound is determined by direct inactivation of the virus and inhibition of virus replication at the early stage, which attests to potential of this compound in the treatment of tick-borne encephalitis. PMID- 29797125 TI - Use of Mesenchymal Stem Cells for Possible Repair of Doxorubicin-Damaged Organs and Tissues in Experimental Monkeys. AB - Three injections of doxorubicin to rhesus macaques cause severe intoxication, characterized by anemia, cachexia, and degeneration of the viscera. The life span of monkeys injected with the drug and receiving after 24 h mesenchymal stem cell transplantation varied from 96 to 120 days in comparison with 50-74 days in animals receiving stem cells before doxorubicin. Controls received doxorubicin and saline; the lifespan of one monkey was 24 days, of the other - 1 year and 8 months. The increase in activity of proinflammatory cytokine IL-6 was paralleled by an increase in the level of C-reactive protein. PMID- 29797126 TI - Loss of Heterozygosity in BRCA1 and BRCA2 Genes in Patients with Ovarian Cancer and Probability of Its Use for Clinical Classification of Variations. AB - Changes (or variants) in BRCA1 and BRCA2 gene sequences can have different lengths and clinical significance: from single nucleotide variants (SNV) and short insertions/deletions (<50 bp) to extended deletions and duplications (so called copy number variations, or CNV). According to their clinical significance, all variants can be divided into pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign. Moreover, variants can be germinal (i.e. inherited from parents) and somatic (arising in the process of development of the organism). A specific somatic event is loss of heterozygosity (LOH), i.e. transition of one or many point and short variants from heterozygous to homozygous state. Such an event can be the key to the development of carcinogenesis for cells carrying a pathogenic variant, if we consider it within the framework of the Knudson's two-hit carcinogenesis theory. We studied the prevalence and nature of LOH in of ovarian cancer samples carrying or not carrying a pathogenic variant. To this end, a full coding sequence of BRCA1/2 genes was determined in 30 pairs of DNA samples isolated from blood cells and paraffinized histological blocks of patients on a MiSeq Illumina instrument. Analyss of the obtained reads revealed 9 pathogenic point and short variants (30% patients): 6 germinal (20%) and 3 somatic (10%), and 8 somatic CNV (3 deletions and 5 duplications of several or all exons of the BRCA1 gene). LOH was detected in 70% patients; among the carriers of pathogenic variants - in 83%. For pathogenic variants, the percentage of reads with the alternative allele increased more often than for benign variants located in another gene, or detected in other patients (67% vs. 44%). However, the difference was statistically insignificant, which can be due to insufficient number of patients. Only in 3 of 21 cases of LOH (14%), it can be attributed to CNV. In other cases, LOH is most likely determined by gene conversion, but further research is needed. PMID- 29797127 TI - Polymorphism of Oprm1 Gene and Its Association with Manifestations of N-(1 Phenethyl-4-Piperidyl)Propionanilide Intoxication in Rats. AB - We studied association of Oprm1 gene polymorphisms with signs of N-(1-phenethyl-4 piperidyl)propionanilide intoxication in rats. It was found that the rate of intoxication in laboratory animals depends on genetic features. A polymorphic variant rs105312806 of Oprm1 gene can be a possible marker of animal sensitivity to opioid receptor agonists. This hypothesis was supported by differences in the rats of intoxication signs such as time to lateral posture and sleep duration in homozygous rats carrying different alleles. In rats with AA genotype, the time to lateral posture was shorter by 1.3 times and sleep duration was longer by 3.5 times than in carriers of GG genotype. PMID- 29797128 TI - Role of JAK/STAT3 Signaling in Functional Stimulation of Mesenchymal Progenitor Cells by Fibroblast Growth Factor. AB - JAK/STAT signaling pathway was examined during functional stimulation of mesenchymal progenitor cells with fibroblast growth factor. The differences were observed in the realizations of the proliferation-differentiation potential of CFU-fibroblasts under blockade of JAKs or during selective inactivation of STAT3. The study revealed stimulating influences of JAKs and STAT3 on mitotic activity of progenitor cells and individual roles of these proteins in the control of their maturation. Blockade of JAKs diminished the level of fibroblast colony formation and the score of actively proliferating CFU-fibroblasts at the background increase of the differentiation rate of progenitor cells. In contrast, STAT3 inhibitor resulted in a coordinated decrease of all examined parameters. PMID- 29797129 TI - Analysis of Blood Plasma Protein Composition in Patients with Cerebral Ischemia. AB - Blood plasma proteome in patients with cerebral ischemia and healthy individuals was studied using comparative proteomic analysis based on tandem HPLC-MS/MS. Mass spectra were analysed in an automated mode using Progenesis LS-MS software and 256 proteins were identified. Significant quantitative differences were revealed for 20 proteins. It was found that changes in the blood plasma proteome in subjects with cerebral ischemia involved a wide range of proteins: molecular chaperones, fibrinolysis, angiogenesis, and immune system proteins, proteins involved in homeostasis maintenance, cell differentiation and proliferation, regulators of apoptosis, and cytoskeleton proteins. PMID- 29797130 TI - Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo. AB - Pronounced antitumor effect of Thymalin in doses lower than the therapeutic doses was shown in experiments on albino outbred male rats with transplanted sarcoma 45. Tumor growth arrest and its regression were observed in more than half of animals and in other cases, the growth was suppressed by 78%. Microstructural changes in the thymus were analyzed. Significant increase in lymphoproliferative activity and the content of tissue basophils and plasmocytes in the thymus lobules was observed. Tumor regression was accompanied by the development of stable antistress adaptation reactions of calm and elevated activation. High efficiency of Thymalin can be attributed to the use of lower doses of the substance and their modulation during the treatment course in accordance with the regimes of activation therapy. PMID- 29797131 TI - N-(5-Hydroxynicotinoil)-L-Glutamic Acid Calcium Salt Modifies Responses of Rat Hippocampal CA1 Pyramidal Neurons during Orthodromic Stimulation. AB - The study examined the effect of calcium salt of N-(5-hydroxynicotinoil)-L glutamic acid (Ampasse preparation) on neuronal activity in hippocampal CA1 area evoked by stimulation of Schaffer collaterals at a rate of 1 Hz (30 impulses during 30 sec) in the surviving hippocampal slices of Wistar rats. The records of 1st and 30th orthodromic population spikes showed that Ampasse in concentrations of 500 MUM, 1, 2, and 10 mM facilitated the synaptic transmission in Schaffer collaterals - hippocampal CA1 pyramidal neurons axis; the maximum effect was observed at 2 mM Ampasse. When used in a concentration of 10 mM, Ampasse provoked epileptiform activity, which could be prevented by MK-801, a specific noncompetitive antagonist of the NMDA-receptor complex. PMID- 29797132 TI - Immunochemical Diagnosis of Multiple Myeloma. AB - The diagnostic potentialities of complex immunochemical analysis of the serum and daily urine were evaluated in 118 patients with multiple myeloma. In 95 patients, we observed secretion of monoclonal intact immunoglobulins with heavy chains G (N=69), A (N=19), and M (N=4) and biclonal secretion of paraproteins G and A (N=3). Bence-Jones protein was detected in the sera and daily urine of 16 patients and Bence-Jones proteinuria alone was detected in 3 patients. The diagnostic sensitivity of serum immunoelectrophoresis in multiple myeloma is 94.1%. Analysis of paraproteinuria is particularly important in Bence-Jones myeloma, when paraprotein excretion may be not associated with paraproteinemia. Complex study by immunoelectrophoretic and immunoturbidimetric methods in multiple myeloma increases the diagnostic sensitivity to 99.2%. PMID- 29797133 TI - New Fluorescent Reporter Systems for Evaluation of the Expression of E- and N Cadherins. AB - During metastatic growth, cells of solid tumors undergo phenotypical changes related to epithelial-mesenchymal transition. Epithelial-mesenchymal transition is regarded as a potential target for prospective antitumor drugs. Fluorescent reporter systems for evaluation of the expression of markers of epithelial and mesenchymal status (E- and N-cadherins) were created. The described approaches can be used for creation of analogous reporter systems. PMID- 29797134 TI - Correction of Cholinergic Abnormalities in Mnestic Processes with Diterpene Alkaloid Songorine. AB - Repeated administration of songorine to mice restored mnestic processes impaired by scopolamine treatment, which manifested in improvement of CPAR conditioning and normalization of behavioral activity throughtout the observation period. This thearpeutical effect surpassed that of pyracetam used as the reference drug. PMID- 29797135 TI - Insulin Increases Viability of Neurons in Rat Cerebral Cortex and Normalizes Bax/Bcl-2 Ratio under Conditions of Oxidative Stress. AB - We studied the protective effect of insulin in various concentrations and its effect on the Bax/ Bcl-2 ratio in neurons of rat cerebral cortex under conditions of oxidative stress. The protective effect of insulin was dose-dependent within the nanomolar range (1 nM<10 nM<100 nM). Preincubation with insulin in concentrations of 100 nM and 1 MUM significantly increased Bcl-2 content in neurons in 5, 30, and 45 min and 1, 2, and 4 h after the start of cell exposure to H2O2. This prooxidant increased the Bax/Bcl-2 ratio in neurons to 141-164% in comparison with the control (100%); preincubation of neurons with insulin returned this ratio to normal. PMID- 29797136 TI - Extracellular NAD+ Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny. AB - The effects of sympathetic cotransmitter NAD+ (10 MUM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 MUM) altered the configuration and significantly lengthened the action potentials. NAD + against the background of norepinephrine stimulation significantly decreased the duration of action potentials, in particular, at 25% repolarization. The effect of purine compounds NAD + , ATP, and adenosine on bioelectrical activity of the heart of newborn rats was studied under basal conditions (without norepinephrine stimulation). The effect of NAD + against the background of adrenergic stimulation was more pronounced than under basal conditions and was probably determined by suppression of ICaL, which can be the main mechanism of NAD + action on rat heart. PMID- 29797137 TI - Vascularization of the Damaged Nerve under the Effect of Experimental Cell Therapy. AB - Quantitative analysis of blood vessels in the distal segment of rat sciatic nerve after its ligation for 40 sec and subperineurial administration of mesenchymal stem cells or dissociated cells of rat embryonic spinal cord was carried our by immunohistochemical tracing of von Willebrand factor, a marker of endothelial cells of blood vessels. It was found that the number of blood vessels per unit area of the nerve trunk in 21 days after injury and administration of mesenchymal stem cells increased by more than 1.5 times in comparison with the control (damaged nerve). After administration of dissociated cells of the embryonic spinal cord, this effect was not observed. It is assumed that mesenchymal stem cells stimulate the growth of vessels of the damaged nerve via production of angiogenic factors. PMID- 29797138 TI - Comparative Analysis of the Expression of Glutathione Peroxidase and Glutathione Reductase Genes in Human Sperm after Cryopreservation. AB - We analyzed the effect of cryopreservation on the expression of glutathione peroxidase (GPX1) and glutathione reductase (GSR) genes in human sperm cells (15 sperm samples from fertile donors and 10 samples from infertile patients). The relative expression of GPX1 and GSR genes was determined by real-time PCR. The rate of post-thaw recovery was 2.1 times higher in the group of fertile donors. A significant increase in the expression of GPX1, but not GSR, was observed in sperm samples from infertile patients, while in patients with infertility, GPX1 expression significantly decreased after cryopreservation/thawing, in samples from fertile donors after the same procedure it increased to the level observed in the sperm samples from infertile patients. A positive correlation was revealed between GPX1 expression and sperm cryotolerance. PMID- 29797140 TI - Mechanical Performance of Two Left Atrial Appendage Occlusion Systems: In Vitro Comparison of Tug Force, Radial Force, Sealing and Deformation. AB - The aim of this study was to establish in vitro bench-tests of left atrial appendage occlusion (LAAo) devices regarding tug force, radial force and sealing capacity. Two LAAo devices, namely the WATCHMANTM and the Occlutech(r), of three different sizes underwent testing in novel dedicated in vitro setups. Radial force was assessed in a commercial radial force tester. At baseline, tug force of the WATCHMANTM was significantly higher when compared to Occlutech(r) for all devices. Repeated resheathing resulted in a reduction of device-diameter in the WATCHMANTM devices of max. 7.9%, whereas diameters of Occlutech(r) occluders remained unchanged. Tug force was not significantly impacted by resheathing in both devices. At baseline, sealing capacity in a bench-test using silicone LAA models did not differ between the devices. Resheathing lead to an in vitro loss of sealing capacity of the WATCHMANTM devices, increasing with resheathing and resulting in a max. peridevice leak of 91.1 +/- 7.9%. Radial force was higher for the Occlutech(r) devices and decreased for WATCHMANTM occluders after resheathing. The WATCHMANTM occluder series showed progressive deformation, increased peridevice leakage and decreased radial force after resheathing, presumably as a result of diameter reduction. Tug force of the WATCHMANTM was not impaired by resheathing and was significantly higher than that of the Occlutech(r) device. PMID- 29797139 TI - A Docosahexaenoic Acid-Derived Pro-resolving Agent, Maresin 1, Protects Motor Neuron Cells Death. AB - Maresin 1 is a novel pro-resolving mediator derived from docosahexaenoic acid (DHA), with potent anti-inflammation effects against several animal models, including brain ischemia, sepsis, and lung fibrosis. However, its effect against motor neuron cell death is still not investigated. Therefore, we investigated the effects of maresin 1 on several stress-induced motor neuron cell death. Maresin 1 suppressed combinatorial stress which was evoked by superoxide dismutase 1 (SOD1)G93A and serum-free, -induced motor neuron cells death in a concentration dependent manner, and had a stronger neuroprotective effective than DHA. Maresin 1 also had neuroprotective effects against transactivation response DNA-binding protein (TDP)-43A315T and serum-free stress, H2O2, and tunicamycin-induced cell death. Maresin 1 reduced the reactive oxygen species (ROS) production caused by SOD1G93A or TDP-43A315T. Moreover, maresin 1 suppressed the NF-kappaB activation induced by SOD1G93A and serum-free stress. These data indicate that maresin 1 has motor neuron protective effects against several stresses by reduction of ROS production or attenuation of the NF-kappaB activation. Maresin 1 also had neuroprotective effects against H2O2, and tunicamycin-induced cell death in a concentration-dependent manner. Finally, maresin 1 ameliorated the motor function deficits of spinal muscular atrophy model in which endoplasmic reticulum stress was upregulated. Thus, maresin 1 may be beneficial to protect against motor neuron diseases. PMID- 29797141 TI - In-Human Robot-Assisted Retinal Vein Cannulation, A World First. AB - Retinal Vein Occlusion (RVO) is a blinding disease caused by one or more occluded retinal veins. Current treatment methods only focus on symptom mitigation rather than targeting a solution for the root cause of the disorder. Retinal vein cannulation is an experimental eye surgical procedure which could potentially cure RVO. Its goal is to dissolve the occlusion by injecting an anticoagulant directly into the blocked vein. Given the scale and the fragility of retinal veins on one end and surgeons' limited positioning precision on the other, performing this procedure manually is considered to be too risky. The authors have been developing robotic devices and instruments to assist surgeons in performing this therapy in a safe and successful manner. This work reports on the clinical translation of the technology, resulting in the world-first in-human robot-assisted retinal vein cannulation. Four RVO patients have been treated with the technology in the context of a phase I clinical trial. The results show that it is technically feasible to safely inject an anticoagulant into a [Formula: see text]-thick retinal vein of an RVO patient for a period of 10 min with the aid of the presented robotic technology and instrumentation. PMID- 29797143 TI - Gastric Cancer in a Patient with Laparoscopic Adjustable Gastric Band: Case Report and Review of Literature. PMID- 29797142 TI - Systemic hematogenous dissemination of mouse oral candidiasis is induced by oral mucositis. AB - The causes of fungemia include immunosuppression and neutropenia stemming from diverse factors as well as the placement of central venous catheters. However, the relationship between fungemia and the oral cavity has not been substantiated. In this study, we explored the pathological conditions of Candida albicans derived oral candidiasis in a mouse model, which always develops oral mucositis as a complication. In oral candidiasis, the hyphae of C. albicans are believed to primarily invade the stratum granulosum, but not the subepithelium, of the mucous membrane. We provide histological evidence that in concomitant oral mucositis, the hyphae infiltrate the subepithelium and blood vessels. Blood cultures and tissue samples revealed the onset of fungemia only in the mucositis-induced groups. Positive numbers of colony-forming units were found in groups A (chemotherapy), B (chemotherapy + mucositis) and C (mucositis), but were highest in group B. Some organs revealed positive CFU in groups B and C. The presence of fungal DNA in blood plasma and tissue was confirmed by PCR. The fungal DNA frequency was significantly higher in the mucositis group when compared with the non-mucositis group. The results suggest that fungi first invade the subepithelium and then the blood vessels, from which they disseminate throughout the body, and that oral mucositis is an important risk factor for fungemia. This study clearly demonstrates the relationship between oral mucositis, fungemia, and the potential systemic fungal dissemination, which has not been previously proven. Our findings highlight the importance of oral care for patients at risk of fungemia. PMID- 29797144 TI - Efficacy of Docetaxel and Oxaliplatin Regimen as a Second-Line Therapy for Patients with Advanced Pancreatic Adenocarcinoma. AB - BACKGROUND AND AIM OF WORK: Pancreatic cancer is the deadliest of the 21 most common cancers, largely because it is often identified at a late stage, we aimed to determine the control rates, and PFS for patients who received docetaxel oxaliplatin regimen as a 2nd line therapy. PATIENTS AND METHODS: Twenty-five patients with advanced cancer pancreas progressed or failed on 1st line treatments and justified the inclusion criteria were eligible to receive Docetaxel 75 mg/m2 over 1h iv infusion on day 1, Oxaliplatin 80 mg/m2 over 2 h iv infusion on day 2, the cycle was repeated every 3 weeks for 6-8 cycles unless disease progression or severe toxicity appeared. RESULTS: No patients achieved complete response (CR), and the control rate (control rate = partial response (PR = 6/25, 24%) + stable disease (SD = 9/25, 36%) was 60% while disease progression (DP) was demonstrated in (10/25) 40% of patients, the median PFS was 7 +/- 0.777 ms (95% confidence interval: 5.467-8.524 ms), grade 3 neutropenia, fatigue, diarrhea, and vomiting were developed in 12%, 8%, 12% and 8% of patients respectively. CONCLUSIONS: Docetaxel-oxaliplatin regimen was an active regimen in advanced cancer pancreas based on our encouraging results without occurrence of grade four toxicities. PMID- 29797145 TI - Giant Duodenal Lipoma: a Rare Cause of Vomiting, Anorexia, Unintentional Weight Loss, and Duodenal Intussusception. PMID- 29797146 TI - Kin Selection and Male Homosexual Preference in Indonesia. AB - Male homosexual preference (MHP) challenges evolutionary thinking because the preference for male-male relationships is heritable, implies a fertility cost (lower offspring number), and is relatively frequent in some societies (2-6% in Western countries) for a costly trait. It has been proposed that individuals with a MHP counterbalance reproductive costs through the transfer of resources to kin, thereby improving their indirect reproduction through kin's reproductive success. This kin selection hypothesis is not supported in Western countries and Japan, although consistent evidence has been obtained in Samoa. In this study, data from Java (Indonesia) were obtained to assess the avuncular tendencies of men with contrasting sexual orientation to measure possible resource transfer. Consistent with the kin selection hypothesis, males with a homosexual orientation reported an increased willingness to transfer resources toward nephews and nieces and declared having transferred more money to nephews and nieces. We developed a method to quantitatively estimate the contribution of kin selection on inclusive reproduction associated to sexual orientation, taking into account various possible biases. Kin selection reduced the direct reproductive cost of homosexual men by 20%, so suggesting that kin selection alone is insufficient to explain the maintenance of male homosexuality. Other potential factors are discussed, as well as the limitations of the study and the social determinant operating for the expression of increased avuncular tendencies of homosexual men. PMID- 29797147 TI - Associations Between Latent Classes of Interpersonal Polyvictimization and Polyperpetration and Sexual Risk Behaviors Among Young Pregnant Couples: A Dyadic Analysis. AB - Interpersonal violence victimization and perpetration have been associated with sexual risk behaviors among adolescents and young adults, but research is lacking on: (1) how patterns of interpersonal polyvictimization and polyperpetration are associated with sexual risk among young pregnant couples, and (2) how individual and partner experiences of violence differentially impact sexual risk. The current analyses used baseline data from a longitudinal study that followed 296 pregnant young couples from pregnancy to 12 months postpartum. Couples were recruited at obstetrics and gynecology clinics, and an ultrasound clinic in the U.S. Latent class analysis identified subgroups based on polyvictimization and polyperpetration. Using the Actor-Partner Interdependence Model, path analyses assessed actor-partner effects of class membership on sexual risk. Three latent classes were used for women: Class 1: Polyvictim-Polyperpetrator; Class 2: Nonvictim-Nonperpetrator; and Class 3: Community and Prior IPV Victim. Four latent classes were used for men: Class 1: Community and Prior IPV Victim; Class 2: Polyvictim-Nonpartner Perpetrator; Class 3: Prior IPV and Peer Victim; and Class 4: Nonvictim-Nonperpetrator. Path analyses revealed that females in Class 2 and their male partners had higher condom use than females in Class 3. Males in Class 2 had more sexual partners than males in Class 1. Among nonmonogamous couples, males in Class 2 were less likely to be involved with a female partner reporting unprotected sex than males in Class 1. Among nonmonogamous couples, females in Class 2 had more acts of unprotected sex than females in Class 1. Males in Class 4 were less likely to have concurrent sexual partners compared to males in Class 1. Risk reduction interventions should address both victimization and perpetration. Additional research is needed to understand how mechanisms driving differential sexual risk by patterns of interpersonal polyvictimization and polyperpetration. PMID- 29797148 TI - Cpf1-assisted efficient genomic integration of in vivo assembled DNA parts in Saccharomyces cerevisiae. AB - OBJECTIVES: To test the applicability of Cpf1 from Francisella novivida in genomic integration of in vivo assembled DNA parts in Saccharomyces cerevisiae. RESULTS: An easy-to-use vector toolkit, containing a CEN6/ARS4 plasmid expressing Cpf1 from Francisella novivida (FnCpf1) and a 2 MU plasmid for crRNA or crRNA array expressing, was constructed for Cpf1-assisted genomic integration in S. cerevisiae. Our results showed that FnCpf1 allowed for targeted singleplex, doubleplex, and tripleplex genomic integration of in vivo assembled DNA parts with efficiencies of 95, 52, and 43%, respectively. CONCLUSIONS: CRISPR-Cpf1 system allows for efficient genomic integration of in vivo assembled DNA parts in S. cerevisiae, and thus provides an alternative CRISPR-Cas method for metabolic pathway engineering in addition to CRISPR-Cas9 system previously reported for yeast. PMID- 29797149 TI - Plant growth-promoting bacterium Pseudomonas fluorescens FR1 secrets a novel type of extracellular polyhydroxybutyrate polymerase involved in abiotic stress response in plants. AB - OBJECTIVES: Identification of novel microbial factors contributing to plant protection against abiotic stress. RESULTS: The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress. CONCLUSION: Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress. PMID- 29797150 TI - The Child and Adolescent Services Assessment: Interrater Reliability and Predictors of Rater Disagreement. AB - The current study evaluated the interrater reliability of the Child and Adolescent Services Assessment (CASA), a widely used structured interview measuring pediatric mental health service use. Interviews (N = 72) were randomly selected from a pediatric effectiveness trial, and audio was coded by an independent rater. Regressions were employed to identify predictors of rater disagreement. Interrater reliability was high for items (> 94%) and summary metrics (ICC > .79) across service sectors. Predictors of disagreement varied by domain; significant predictors indexed higher clinical severity or social disadvantage. Results support the CASA as a reliable and robust assessment of pediatric service use, but administrators should be alert when assessing vulnerable populations. PMID- 29797151 TI - Informing Federal Policy on Firearm Restrictions for Veterans with Fiduciaries: Risk Indicators in the Post-Deployment Mental Health Study. AB - This article examines the public safety rationale for a federal policy of prohibiting gun sales to veterans with psychiatric disabilities who are assigned a fiduciary to manage their benefits from the Department of Veterans Affairs. The policy was evaluated using data on 3200 post-deployment veterans from the Iraq and Afghanistan war era. Three proxy measures of fiduciary need-based on intellectual disability, drug abuse, or acute psychopathology-were associated in bivariate analysis with interpersonal violence and suicidality. In multivariate analysis, statistical significance remained only for the measure based on acute psychopathology. Implications for reforms to the fiduciary firearm restriction policy are discussed. PMID- 29797152 TI - Monitoring of glyphosate and AMPA in soil samples from two olive cultivation areas in Greece: aspects related to spray operators activities. AB - The persistence of glyphosate and its primary metabolite AMPA (aminomethylphosphonic acid) was monitored in two areas in Southern Greece (Peza, Crete and Chora Trifilias, Peloponnese) with a known history of glyphosate use, and the levels of residues were linked to spray operators' activities in the respective areas. A total of 170 samples were collected and analysed from both areas during a 3-year monitoring study. A new method (Impact Assessment Procedure - IAP) designed to assess potential impacts to the environment caused by growers' activities, was utilised in the explanation of the results. The level of residues was compared to the predicted environmental concentrations in soil. The ratio of the measured concentrations to the predicted environmental concentrations (MCs/PECs) was > 1 in Chora the first 2 years of sampling and < 1 in the third year, whilst the MCs/PECs ratio was < 1 in Peza, throughout the whole monitoring period. The compliance to the instructions for best handling practices, which operators received during the monitoring period, was reflected in the amount of residues and the MCs/PECs ratio in the second and especially the third sampling year. Differences in the level of residues between areas as well as sampling sites of the same area were identified. AMPA persisted longer than the parent compound glyphosate in both areas. PMID- 29797153 TI - Quick, safe, and effective maneuver to prevent phrenic nerve injury during cryoballoon ablation of atrial fibrillation. AB - PURPOSE: Phrenic nerve (PN) injury is a typical complication of cryoballoon ablation (CBA) of pulmonary veins. The PN function is monitored by palpating the abdomen during PN pacing, and freezing is prematurely terminated when a reduction in the diaphragm movement is recognized. This study aimed to investigate the efficacy and safety of a "pull-back" maneuver to prevent PN injury. METHODS: A total of 284 patients were included, and the PN function was monitored by recording the diaphragmatic compound motor action potentials (CMAP) during the cryoballoon applications for pulmonary vein (PV) isolation. When the CMAP amplitude was reduced by more than 30% compared to the control, the "pull-back" maneuver (PBM) was undertaken to prevent PN injury. RESULTS: The average CMAP amplitude significantly decreased from 0.81 +/- 0.04 to 0.31 +/- 0.21 (p < 0.01) mV during the cryoballoon applications of PVs in 92 PVs. The PBM was employed in all cases, and the average CMAP amplitude recovered to 0.87 +/- 0.31 mV (p < 0.01) in 79 out of 92 PVs (85.9%), accomplishing the CBA. Cryofreezing had to be prematurely terminated due to failure of the PBM in 13 out of 92 cases (14.1%). CONCLUSIONS: The PBM was an effective maneuver to prevent PN injury by creating a distance between the PN and location of the cryoballoon. No adverse events were provoked by this procedure. PMID- 29797155 TI - Neuromodulating Attention and Mind-Wandering Processes with a Single Session Real Time EEG. AB - Our minds are continuously alternating between external attention (EA) and mind wandering (MW). An appropriate balance between EA and MW is important for promoting efficient perceptual processing, executive functioning, decision making, auto-biographical memory, and creativity. There is evidence that EA processes are associated with increased activity in high-frequency EEG bands (e.g., SMR), contrasting with the dominance of low-frequency bands during MW (e.g., Theta). The aim of the present study was to test the effects of two distinct single session real-time EEG (rtEEG) protocols (SMR up-training/Theta down-training-SMR?Theta?; Theta up-training/SMR down-training-Theta?SMR?) on EA and MW processes. Thirty healthy volunteers were randomly assigned to one of two rtEEG training protocols (SMR?Theta?; Theta?SMR?). Before and after the rtEEG training, participants completed the attention network task (ANT) along with several MW measures. Both training protocols were effective in increasing SMR (SMR?Theta?) and theta (Theta?SMR?) amplitudes but not in decreasing the amplitude of down-trained bands. There were no significant effects of the rtEEG training in either EA or MW measures. However, there was a significant positive correlation between post-training SMR increases and the use of deliberate MW (rather than spontaneous) strategies. Additionally, for the Theta?SMR? protocol, increase in post-training Theta amplitude was significantly associated with a decreased efficiency in the orientation network. PMID- 29797157 TI - The Resolution Axis Method (RAM) for lengthening of the femur with or without associated frontal plane deformity (a new method). AB - INTRODUCTION: Femoral lengthening with or along intramedullary (IM) nails will occur along the axis of the nail coincident with the anatomical axis of the bone. In the femur particularly, such lengthening often creates lateral mechanical axis deviation as the knee is driven medially. In cases where shortening is associated with frontal plane deformity the surgeon needs to correct the deformity intra operatively, however, subsequent lengthening along the anatomical axis will create deformity. Thus, planning for lengthening of the femur with or along IM nails, whether shortening is associated with frontal plane deformity or not, requires a completely different planning strategy. The author questioned if a resolution anatomical axis can be identified and used for planning when lengthening the femur along or with IM nails while still applying the same classic CORA deformity analysis method. METHODS: In a prospective study, the author included eight patients who needed femoral lengthening, five with associated frontal plane deformity and three without. The author identified a method to determine the trajectory of the nail in the lower femoral segment. It was done by calculating the angle enclosed between this resolution anatomical axis and the mechanical axis, also known as the anatomical-mechanical angle. RESULTS: This new method has proven to be effective in achieving normal alignment after lengthening is completed. CONCLUSION: The Resolution Axis Method is a new and alternative method providing a solution for planning when lengthening the femur along the anatomical axis using an IM nail, whether a deformity is present or not. PMID- 29797154 TI - Transcriptome profiling analysis reveals the role of latrophilin in controlling development, reproduction and insecticide susceptibility in Tribolium castaneum. AB - Latrophilin of Tribolium castaneum (Tclph) has been reported to play crucial roles in growth, development and reproduction. However, the regulatory mechanism of Tclph associated with these physiology processes is unknown. Thus, the global transcriptome profiles between RNAi treated (ds-Tclph) and control larvae of T. castaneum were analyzed by RNA-sequencing. Totally, 274 differentially expressed genes (DEGs) were identified between the ds-Tclph and control samples. These DEGs were classified into 42 GO functional groups, including developmental process, reproduction and stress response. The results indicated that knockdown of Tclph disturbed the antioxidant activity process, and partially inhibited the serine protease (SP) and lipase signaling pathways to regulate the development and reproduction as well as the decreasing of the stress response in T. castaneum. Additionally, knockdown of Tclph suppressed IMD immunity pathways which likely modulated the effects of Tclph on stress response. Interestingly, CSPs, ESTs, CYPs, AOXs and BGs were significantly down-regulated in ds-Tclph larvae, implying that they cooperated with Tclph to reduce the activity of cellular metabolism system. FMOs was up-regulated in ds-Tclph insects suggested it may be involved in detoxifying alkaloid of insect metabolism system. These results implied that Tclph participated in phase 0, I and II cellular detoxification. Furthermore, RNAi against Tclph increased larval susceptibility to carbamates and organophosphates insecticides, supporting that Tclph was indeed involved into the insecticide susceptibility in T. castaneum. PMID- 29797158 TI - Drought and Distress in Southeastern Australia. AB - Droughts may increase the risk of mental health problems, but evidence suggests a complex story with some groups being vulnerable while others are not. Previous studies from Australia have found associations with suicide, depression and distress that vary by age, gender and remoteness. Understanding the effects of drought on mental health is important because drought is predicted to be more intense in some areas in the future. We investigated the associations between drought and distress in a survey of rural Australians by age, gender and farming status. We collected distress data using a survey of 5312 people from across the state of Victoria, Australia, in 2015. Respondents completed the Kessler 10 (K10) Psychological Distress Index, and demographic and general health data were collected. We linked a climatic drought index to the locality of residence of respondents. Associations between distress and drought were analyzed using multivariable regression models with interactions by age, gender and farming occupation. Parts of Victoria were in drought in 2015. Drought duration was associated with higher distress in younger rural women (aged 40-54: odds ratio 1.18 per inter-quartile range increase in drought duration) but not older rural women or men. This pattern did not vary between farmers and non-farmers. Drought was associated with increased distress, but this differed between subgroups. Our results suggest that supporting younger women may be particularly important, and understanding ways older Australian rural women cope may enable us to build adaptive capacity and resilience. PMID- 29797156 TI - The Relation Between Trait Anger and Impulse Control in Forensic Psychiatric Patients: An EEG Study. AB - Inhibitory control is considered to be one of the key factors in explaining individual differences in trait anger and reactive aggression. Yet, only a few studies have assessed electroencephalographic (EEG) activity with respect to response inhibition in high trait anger individuals. The main goal of this study was therefore to investigate whether individual differences in trait anger in forensic psychiatric patients are associated with individual differences in anger primed inhibitory control using behavioral and electrophysiological measures of response inhibition. Thirty-eight forensic psychiatric patients who had a medium to high risk of recidivism of violent and/or non-violent behaviors performed an affective Go/NoGo task while EEG was recorded. On the behavioral level, we found higher scores on trait anger to be accompanied by lower accuracy on NoGo trials, especially when anger was primed. With respect to the physiological data we found, as expected, a significant inverse relation between trait anger and the error related negativity amplitudes. Contrary to expectation, trait anger was not related to the stimulus-locked event related potentials (i.e., N2/P3). The results of this study support the notion that in a forensic population trait anger is inversely related to impulse control, particularly in hostile contexts. Moreover, our data suggest that higher scores on trait anger are associated with deficits in automatic error-processing which may contribute the continuation of impulsive angry behaviors despite their negative consequences. PMID- 29797159 TI - Descriptive Modeling of the Dynamical Systems and Determination of Feedback Homeostasis at Different Levels of Life Organization. AB - The state-of-art research in the field of life's organization confronts the need to investigate a number of interacting components, their properties and conditions of sustainable behaviour within a natural system. In biology, ecology and life sciences, the performance of such stable system is usually related to homeostasis, a property of the system to actively regulate its state within a certain allowable limits. In our previous work, we proposed a deterministic model for systems' homeostasis. The model was based on dynamical system's theory and pairwise relationships of competition, amensalism and antagonism taken from theoretical biology and ecology. However, the present paper proposes a different dimension to our previous results based on the same model. In this paper, we introduce the influence of inter-component relationships in a system, wherein the impact is characterized by direction (neutral, positive, or negative) as well as its (absolute) value, or strength. This makes the model stochastic which, in our opinion, is more consistent with real-world elements affected by various random factors. The case study includes two examples from areas of hydrobiology and medicine. The models acquired for these cases enabled us to propose a convincing explanation for corresponding phenomena identified by different types of natural systems. PMID- 29797160 TI - "Closing the Loop" Developing State-Level Data Sharing Interventions to Promote Optimum Outcomes Along the HIV Continuum of Care. AB - This manuscript describes the experiences of three state departments of health (SDoH) that successfully launched data sharing interventions involving surveillance and/or patient data collected in clinics to improve care outcomes among people living with HIV. We examined 58 key informant interviews, gathered at two time points, to describe the development and implementation of data sharing interventions. We identified three common themes across states' experiences: creating standard practices, fostering interoperability, and negotiating the policy environment. Projects were successful when state teams adapted to changing circumstances and were committed to a consistent communication process. Once implemented, the interventions streamlined processes to promote linkage and retention in care among low-income populations living with HIV. Despite using routinely collected data, key informants emphasized the labor intensive process to develop and sustain the interventions. Lessons learned from these three state experiences can help inform best practices for other SDoH that are considering launching similar interventions. PMID- 29797161 TI - Female Gender and HIV Transmission Risk Behaviors Among People Living with HIV Who Have Ever Used Injection Drugs in St. Petersburg, Russia. AB - Among persons who inject drugs, women have a higher HIV prevalence (than men) in many settings. Understanding how gender affects risk for infection among HIV negative, and transmission among HIV-positive people who currently or previously injected drugs is key to designing effective prevention and treatment programs. We analyzed data from 291 persons living with HIV who had ever injected drugs. Participants were drawn from the Russia Alcohol Research Collaboration on HIV/AIDS cohort (2012-2015) to examine associations between female gender and HIV transmission risk. Primary outcomes were sharing drug injecting equipment (e.g., needle/syringes) and condomless sex. Secondary outcomes were alcohol use before sharing drug injecting equipment; before condomless sex; and both sharing drug injecting equipment and condomless sex. Logistic regression models assessed associations between gender and outcomes, controlling for demographics, partner HIV status and use of antiretroviral treatment. Female gender was not significantly associated with sharing drug injecting equipment [aOR = 1.45, 95% confidence interval (CI) 0.85-2.46, p value = 0.18] but was associated with condomless sex (aOR = 1.91, 95% CI 1.12-3.23, p = 0.02) in adjusted models. Female gender was not significantly associated with any secondary outcomes. Better understanding of risky sex and drug use behaviors among people who currently or previously injected drugs can support the design of effective gender tailored HIV prevention interventions. PMID- 29797162 TI - Missed Opportunities for HIV Prevention: Individuals Who HIV Seroconverted Despite Accessing Healthcare. AB - Individuals with a negative HIV test before a positive one (seroconverters) may represent missed opportunities for prevention. To inform HIV prevention strategies, we aimed to characterize patients who seroconverted despite accessing care. We identified patients at a large, urban healthcare system who seroconverted between 2009 and 2014. Demographics, visits, and HIV-related variables were extracted from the medical records. We performed descriptive statistics, assessed for trends, and tested for associations according to sex. 220 seroconverters were identified: 45% were female, 87% were non-Hispanic Black or Hispanic, and median number of negative tests prior to diagnosis was 2 (IQR 1 3). Overall, 49% reported heterosexual contact as their risk factor and the proportion with heterosexual risk increased over time (24% in 2009 vs. 56% in 2014, p = 0.03). Compared to men, women were older at the time of diagnosis (35 vs. 26 years old, p < 0.01), had more visits between their latest negative and positive HIV test (4 vs. 2, p < 0.01), and were more likely to be diagnosed in the context of screening (64% vs. 56%, p = 0.05). We identified a population that became HIV-infected despite multiple healthcare encounters and undergoing HIV testing multiple times. Patients were mostly heterosexual and almost half were female. To avoid missed opportunities for those already accessing care, HIV prevention efforts should include strategies tailored to individuals with less frequently recognized risk profiles. PMID- 29797163 TI - Collecting Mobility Data with GPS Methods to Understand the HIV Environmental Riskscape Among Young Black Men Who Have Sex with Men: A Multi-city Feasibility Study in the Deep South. AB - While research increasingly studies how neighborhood contexts influence HIV among gay, bisexual and other men who have sex with men (MSM) populations, to date, no research has used global positioning system (GPS) devices, an innovative method to study spatial mobility through neighborhood contexts, i.e., the environmental riskscape, among a sample of Black MSM. The purpose of this study was to examine the feasibility of collecting two-week GPS data (as measured by a pre- and post surveys as well as objectively measured adherence to GPS protocol) among a geographically-diverse sample of Black MSM in the Deep South: Gulfport, MS, Jackson, MS, and New Orleans LA (n = 75). GPS feasibility was demonstrated including from survey items, e.g. Black MSM reported high ratings of pre-protocol acceptability, ease of use, and low levels of wear-related concerns. Findings from this study demonstrate that using GPS methods is acceptable and feasible among Black MSM in the Deep South. PMID- 29797165 TI - The modified Dunn procedure provides superior short-term outcomes in the treatment of the unstable slipped capital femoral epiphysis as compared to the inadvertent closed reduction and percutaneous pinning: a comparative clinical study. AB - PURPOSE: The aim of this study was to compare clinical outcomes and radiographic correction after modified Dunn procedure versus inadvertent closed reduction and percutaneous pinning for the treatment of unstable slipped capital femoral epiphysis (SCFE). METHODS: We evaluated 45 patients with unstable SCFE treated using the modified Dunn procedure (n = 27) or percutaneous pinning (n = 18) during a minimum follow-up of one year. Clinical outcomes were assessed using the Heyman and Herndon scores. The Southwick angle, alpha angle, and femoral head neck offset were used to assess radiographic correction. The occurrence of complications and unplanned re-operations were recorded. RESULTS: At latest follow-up, 67% (18/27) in the modified Dunn procedure group and 28% (5/18) in the in situ pinning group had good or excellent Heyman and Herndon outcomes (p = 0.016). The morphology of the femoral head and neck was improved in the modified Dunn procedure group compared to percutaneous pinning (Southwick angle, alpha angles; femoral head-neck offset; p < 0.001). The proportion of osteonecrosis (26 vs. 28%; p > 0.999) and unplanned re-operations (26 vs. 33%; p = 0.894) was similar in both groups. CONCLUSION: Compared to inadvertent reduction and percutaneous pinning, the modified Dunn procedure provided better clinical and radiographic outcomes with similar proportion of osteonecrosis and unplanned re operations following an unstable SCFE. PMID- 29797164 TI - Mechanism of Resistance to Camptothecin, a Cytotoxic Plant Secondary Metabolite, by Lymantria sp. Larvae. AB - Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic topoisomerase I (Top 1). Because of this property, several derivatives of CPT are widely used as chemotherapeutic agents. The compound is produced by several plant species, including Nothapodytes nimmoniana (Family: Icacinaceae) presumably as a deterrent to insect pests. Here, we report, a lepidopteran larva, Lymantria sp. of Lymantriidae family which feeds voraciously on the leaves of N. nimmoniana, without any adverse consequences. Larval body weight and molting period were unaffected despite captive feeding of the larva with CPT enriched leaves. Mass spectrometric analysis indicated that nearly 46% of the ingested CPT was excreted while the rest was sequestered predominantly in the exuviae and setae (~35%). Although most of the CPT was in the parental form as found in the plant, traces of inactive, sulfated forms of CPT were recovered from the larva. Compared to that in plant, there were no critical mutations at the CPT binding domain of the insect's Top 1. The gut pH of the larva was alkaline (pH 10.0). The alkaline gut environment converts CPT from its active, lactone form to inactive, carboxylate form. It is likely that such conversion might help the larva to reduce the overall burden of CPT in its gut. We discuss the results in the context of the mechanisms of resistance adapted by insects to plant toxins. PMID- 29797166 TI - Strength of suture-button fixation versus ligament reconstruction in syndesmotic injury: a biomechanical study. AB - PURPOSE: To compare the biomechanical characteristics of suture-button fixation versus ligament reconstruction using semitendinosus tendon autograft in treatment of syndesmotic injury in cadaver biomechanical study. METHODS: Eight matched pairs of human cadaveric lower-extremities were measured intact, then following simulated syndesmosis injury by cutting the anterior tibiofibular ligament (AITFL), the distal 15 cm of the interosseous membrane (IO), and the deltoid ligament. Thereafter, the syndesmotic injury was treated by suture-button fixation or ligament reconstruction. The semitendinosus tendon was harvested as a graft. Biomechanical testing was performed after the surgical fixation. The foot underwent rotation from neutral position to an external rotation at a rate of 5 degrees /s to 12.5 Nm. The three-dimensional syndesmotic diastasis readings, final rotation torque, and rotational angle were recorded. RESULTS: No difference was found in fibular displacements between two groups. Moreover, no significant difference was found in final rotation torque (11.95 +/- 1.03 VS 11.66 +/- 1.18 Nm, P = 0.62) and rotation angle (43.61 degrees +/- 14.77 degrees VS 40.93 degrees +/- 10.94 degrees , P = 0.56) in the suture-button group and ligament reconstruction group. CONCLUSION: The stability of the suture-button fixation was equivalent to ligament reconstruction using semitendinosus tendon autograft in treatment of syndesmotic injury as determined with biomechanical testing. However, this study does not prove that one is advantageous over the other. PMID- 29797167 TI - Cementless total hip arthroplasty for osteonecrosis and osteoarthritis produce similar results at ten years follow-up when matched for age and gender. AB - PURPOSE: The aim of this study was to compare the clinical outcomes of cementless total hip arthroplasty (THA) used for the treatment of osteonecrosis of the femoral head (ONFH) and for osteoarthritis (OA) at a mean ten years follow-up. METHODS: Case-control study of 78 patients (86 hips) who underwent THA for ONFH treatment (ONFH group). Patients were matched for age and sex to 78 patients (86 hips) who underwent THA for OA (OA group). We compared the clinical and patient reported outcomes, implant survival rates, and rates of complications between the groups. RESULTS: There were no between-group differences in the Harris Hip Score and in the following patient-reported outcomes at the last follow-up: Japanese Orthopedic Association Hip-Disease Evaluation Questionnaire (JHEQ) pain and movement scores and the Physical Component Summary and Role/Social Component Summary scores of Short Form-36 (SF-36). However, the mental score of the JHEQ, the Mental Component Summary score of SF-36, and The Visual Analog Scale score for satisfaction were lower for the ONFH group than for OA group. The rate of complication was equivalent between the groups: 5% for the ONFH group and 3% for the OA group. The ten year implant survival rate was equivalent between the groups, at 97.5% for the ONFH group and 98.2% for the OA group. CONCLUSION: The functional outcomes, implant survival, and rate of complications for cementless THAs are comparable at a mean follow-up of ten years for ONFH and OA. PMID- 29797168 TI - The role of autophagy in steroid necrosis of the femoral head: a comprehensive research review. AB - Steroid-induced osteonecrosis of the femoral head (ONFH) has the incidence of 9 40% in patients receiving long-term treatment and is mainly involved in the middle and young people. It is mostly bilateral, with a wide range of necrosis and high disability rate, which brings disaster for patients and families. The experimental study shows that autophagy participates in the pathological process of steroid ONFH and is closely related to apoptosis, and the interaction between autophagy and bone cells is related to the dose of hormones. Moreover, autophagy also affects the interaction between osteoblasts and osteoclasts in ONFH. In the present review, we have discussed the role of autophagy in the pathological process of the steroid-induced ONFH. PMID- 29797169 TI - Predation and behavioral changes in the neotropical lacewing Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) exposed to lambda-cyhalothrin. AB - Pyrethroid insecticides are widely recommended against various defoliating pest species, but usually lack efficacy against sucking pests such as aphids, which are preferred prey of lacewing larvae. Interaction of pyrethroids and lacewings are likely to occur in fields infested by both defoliating and sap-sucking pests and should provide a complementary control. Therefore, our study aimed to estimate dose-mortality curves and behavioral changes by Chrysoperla externa exposed to lambda-cyhalothrin. We tested the susceptibility of two populations from different locations and insecticide history exposure through topical application. Based on the LD50-calculated, the population exhibiting the greater LD50 was exposed to resistance enhancement (Sel) by treating larvae once for seven successive generations. The population with lower LD50 was kept without selection (Nsel). Subsequently, walking, predation and oviposition behavioral after exposure to dried insecticide residues were investigated. After seven generations with insecticide selection, the resistance rations between Sel and Nsel populations were 5.85- and 9.37-fold higher for larvae and 3.38- and 2.75 fold higher for adults, respectively. Selected females caged in partially treated arenas laid similar eggs number on both treated and untreated surfaces, while Nsel females laid fewer eggs on treated surfaces. Insecticide repellency was not observed in either population, although irritability was observed for Nsel larvae. Selected larvae confined on fully and partially treated surfaces walked further, for a longer time, and with greater speeds compared to Nsel larvae. Furthermore, Sel and Nsel larvae had reduced predation rates when confined on treated surfaces, and Nsel larvae consumed less prey than Sel larvae. Results indicate changes in susceptibility, behavior, and predation rate of C. externa following exposure to lambda-cyhalothrin. PMID- 29797170 TI - Non-target toxicity of synthetic insecticides on the biological performance and population growth of Bracon hebetor Say. AB - Bracon hebetor Say (Hymenoptera: Braconidae) is an important biological control agent of various species of order Lepidoptera and extensively used in biological control program worldwide. Present study evaluated the lethal and sublethal effects of insecticides on B. hebetor using demographic and population growth parameters. Doses of all the tested insecticides were within a maximum range of their recommended field dosages and adults were treated using residual glass vials method. For control experiments adults were treated with distilled water. Among the tested insecticides, the survivorship of various stages of B. hebetor was considerably prolonged on cyantraniliprole followed by chlorantraniliprole and shortest on chlorpyrifos and profenofos treated group. Total immature development time was prolonged in chlorpyrifos and profenofos treated group. Population growth parameters like intrinsic rate of natural increase (rm), net reproductive rate (R0), finite rate of increase (lambda) and mean generation time (Tc) were considerably reduced in B. hebetor groups treated with chlorpyrifos and profenofos. However, B. hebetor groups treated with chlorantraniliprole and cyantraniliprole showed a little or no much difference in population growth parameters when compared with untreated group. It was also observed that chlorpyrifos and profenofos modified the sex ratio, thereby female emergence get reduced. On the basis of present findings it can be concluded that all tested insecticides caused considerable ecotoxic effects on B. hebetor compared to control. However, comparisons among the tested insecticides on the basis of IOBC criteria showed that chlorantraniliprol and cyntraniliprol was less toxic as compared to other insecticides tested on this biological control agent. PMID- 29797171 TI - Morphological, physiological and molecular responses of Nitzschia palea under cadmium stress. AB - The impact of cadmium on the diatom Nitzschia palea (Kutzing) W. Smith 1856 was studied by examining the relation between valve deformities and response through biological processes and genetic expression. Cultures of N. palea were exposed to two Cd treatments (C1 = 2.4 +/- 0.6 and C2 = 42.6 +/- 4.2 ug Cd/L) along with a control (C0 = 0 ug Cd/L) for 28 days. Cadmium bioaccumulation, diatoms growth, photosynthetic efficiencies, valve deformities and genetic expression were investigated during the course of the experiment. Cadmium exposure had significant effects on bioaccumulation, growth, valve deformities and genetic expression. Maximal effects for all studied endpoints were recorded after 7 days of exposure for the C2 treatment, which corresponded to the sampling time and condition with maximum cadmium bioaccumulation. Abnormal raphe formations (deviation from its lateral position) were significantly more abundant in the C2 treatment compared to the control. Molecular responses were related to cadmium level based on the number of genes impacted, intensity of the response and the frequency of observations. The expression of genes involved in the regulation of mitochondrial metabolism, photosynthesis, oxidative stress and silica metabolism was affected by cadmium exposure. PMID- 29797172 TI - Enhancing the human dimensions of children's neuromuscular care: piloting a methodology for fostering team reflexivity. AB - For those with chronic, progressive conditions, high quality clinical care requires attention to the human dimensions of illness-emotional, social, and moral aspects-which co-exist with biophysical dimensions of disease. Reflexivity brings historical, institutional, and socio-cultural influences on clinical activities to the fore, enabling consideration of new possibilities. Continuing education methodologies that encourage reflexivity may improve clinical practice and trainee learning, but are rare. We piloted a dialogical methodology with a children's rehabilitation team to foster reflexivity (patient population: young people with Duchenne's or Becker's muscular dystrophy). The methodology involved three facilitated, interactive dialogues with the clinical team. Each dialogue involved clinicians learning to apply a social theory (Mol's The Logic of Care) to ethnographic fieldnotes of clinical appointments, to make routine practice less familiar and thus open to examination. Discourse analyses that preserve group dynamics were completed to evaluate the extent to which the dialogues spurred reflexive dialogue within the team. Overall, imagining impacts of clinical care on people's lives-emphasized in the social theory applied to fieldnotes-showed promise, shifting how clinicians interpreted routine practices and spurring many plans for change. However, this reflexive orientation was not sustained throughout, particularly when examining entrenched assumptions regarding 'best practices'. Clinicians defended institutional practices by co constructing the metaphor of balancing logics in care delivery. When invoked, the balance metaphor deflected attention from emotional, social, and moral impacts of clinical care on patients and their families. Emergent findings highlight the value of analysing reflexivity-oriented dialogues using discourse analysis methods. PMID- 29797173 TI - Anti-inflammatory activity of dimethyl octenol and oleanene tetrol isolated from Trianthema decandra L. AB - Dimethyl octenol from chloroform extract and oleanene tetrol from water extract of Trianthema decandra (TD) were isolated and characterized by using HPLC, UV, FT IR, NMR, LC-MS and CHNS, their structure were elucidated from their respective spectral data. The anti-inflammatory activity of chloroform extract, water extract, dimethyl octenol and oleanene tetrol of T. decandra were studied and underlying cellular and molecular mechanisms of action were investigated in vitro and in vivo using macrophage-like cell line (RAW264.7 cells) and type II collagen induced arthritis mice models. Nitric oxide production was inhibited and TNF alpha secretion was supressed in stimulated RAW cells treated with the chloroform extract and dimethyl octenol of T. decandra. Further, the chloroform and water extract, dimethyl octenol and oleanene tetrol inhibited protein denaturation and stabilized HRBC membranes in vitro. Reduction in inflammation as a measure of paw diameter was recorded in all the treated animals when compared to control animals. Catalase, peroxidase and glutathione peroxidase levels significantly increased in the joint tissue of treated groups. The possible mechanism of action of these compounds was studied using in silico molecular docking methods with phospholipase A2 (PLA2), cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2) as targets. Among the three target proteins, the inhibition of the inflammatory protein PLA2 and COX-2 towards dimethyl octenol and oleanene tetrol respectively. Our results contribute towards confirmation of the traditional use of TD and its compounds for the therapy of rheumatoid arthritis and other inflammatory joint disorders. PMID- 29797174 TI - Cytotoxicity of doxrubicin loaded single-walled carbon nanotubes. AB - Carbon nanotube (CNTs) is a new alternative for efficient drug delivery and it has a great potential to change drug delivery system profile in pharmaceutical industry. One of the important advantage of CNTs is their needle-like, cylindrical shape. This shape provides a high surface area for multiple connections and adsorption onto for millions of therapeutic molecules. CNTs can be internalized by cells via endocytosis, passive diffusion and phagocytosis and release the drug with different effects like pH and temperature. The acidic nature of cancer cells and the susceptibility of CNTs to release the drug in the acidic environment have made it a promising area of research in cancer drug delivery. In this research, we investigated cell viability, cytotoxicity and drug delivery in breast cancer cell line by designing non-covalent single walled carbon nanotubes (SWNT)-doxorubicin (DOX) supramolecular complex that can be developed for cancer therapy. Applied high concentrations of DOX loaded SWNTs changed the actin structure of the cells and prevented the proliferation of the cells. It was showed that doxorubicin loaded SWNTs were more effective than free doxorubicin at relatively small concentrations. Once we applied same procedure for short and long (short: 1-1.3 um; long: 2.5-4 um) SWNTs and compared the results, more disrupted cell structure and reduction in cell proliferation were observed for long CNTs. DOX is bounded more to nanotubes in basic medium, less bound in acidic environment. Cancer cells were also examined for concentration at which they were effective by applying DOX and it was seen that 3.68 uM doxorubicin kills more than 55% of the cells. PMID- 29797176 TI - SF-6D population norms for the Hong Kong Chinese general population. AB - PURPOSE: To estimate population norms for the SF-6D health preference (utility) scores derived from the MOS SF-36 version 1 (SF-36v1), SF-36 version 2 (SF-36v2), and (SF-12v2) health surveys collected from a representative adult sample in Hong Kong, and to assess differences in SF-6D scores across sociodemographic subgroups. METHODS: A random telephone survey of 2410 Chinese adults was conducted. All respondents completed questionnaires on sociodemographics and presence of chronic diseases (hypertension, diabetes, chronic rheumatism, chronic lung diseases, stroke, and mental illness), and the short-form 36-item health survey (SF-36) version 1, and selected items of the SF-36v2 that were different from those of SF-36v1. Responses of short-form 12-item health survey (SF-12) were extracted from responses of the SF-36 items. SF-6D health utility scores were derived from SF-36 version 1 (SF-6DSF-36v1), SF-36 version 2 (SF-6DSF-36v2), and SF-12 version 2 (SF-6DSF-12v2) using Hong Kong SF-6D value set. RESULTS: Population norms of SF-6DSF-36v1, SF-6DSF-36v2, and SF-6DSF-12v2 for the Hong Kong Chinese were 0.7947 (+/- 0.0048), 0.7862 (+/- 0.0049), and 0.8147 (+/- 0.0050), respectively. Three SF-6D scores were highly correlated (0.861-0.954), and had a high degree of reliability and absolute agreement. Males had higher health utility scores (SF-6DSF-36v1: 0.0025; SF-6DSF-36v2: 0.025; SF-6DSF-12v2: 0.018) but reported less problems in all the dimensions than women. Respondents with a higher number of chronic diseases had lower SF-6D scores. Among all respondents with one or more chronic diseases, those with hypertension scored the highest whereby those with mental illness scored the least. CONCLUSIONS: The SF 6D utility scores derived from different SF-36 or SF-12 health surveys were different. The population norms based on these three health surveys enable the normative comparisons of health utility scores from specific population or patient groups, and provide estimates of age-gender adjusted health utility scores for health economic evaluations. PMID- 29797175 TI - Combining online and in-person methods to evaluate the content validity of PROMIS fatigue short forms in rheumatoid arthritis. AB - PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p >= .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r >= 0.82; p < .000) and moderately with patient assessments of disease activity (r >= 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (>= 94%) could distinguish general fatigue from RA fatigue. Most (>= 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA. PMID- 29797177 TI - Third molar removal and its impact on quality of life: systematic review and meta analysis. AB - OBJECTIVE: The purpose of this systematic review was to assess the impact of third molar removal on patient's quality of life. METHODS: To address the study purpose, investigators designed and implemented a systematic review. The primary outcome variable was the quality of life after third molar extraction. An electronic search was conducted through March, 2017, on the PUBMED, Virtual Health Library (VHL), Web of Science, and OVID, to identify relevant literatures. Research studies (randomized or non-randomized clinical trials) were included that evaluated the quality of life in individuals before and after third molar extraction, using validated measures of oral health-related quality of life with quantitative approach, besides procedures performed under local anesthesia. The R software was used to measure the mean difference on the quality of life between the preoperative period and follow-up days. RESULTS: A total of 1141 studies were identified. Of this total, 13 articles were selected in the present systematic review, of which six studies were included in the meta-analysis. All of these 13 articles used the OHIP-14, and 4 of this 13 used OHQoLUK-16 to evaluate the quality of life. Regarding quality assessment, four of the 13 included studies in this review received a maximum score of 9 points, according to the Newcastle Ottawa (NOS). The OHIP-14 mean score on the first postoperative day was 17.57 (95% CI 11.84-23.30, I2 = 96%) higher than the preoperative period. On the seventh postoperative day, the quality of life assessed by OHIP-14 got worse again. CONCLUSION: This systematic review revealed that the highest negative impact on quality of life of individuals submitted to third molar surgery was observed on the first postoperative day, decreasing over the follow-up period. PMID- 29797178 TI - Generalized Processing Tree Models: Jointly Modeling Discrete and Continuous Variables. AB - Multinomial processing tree models assume that discrete cognitive states determine observed response frequencies. Generalized processing tree (GPT) models extend this conceptual framework to continuous variables such as response times, process-tracing measures, or neurophysiological variables. GPT models assume finite-mixture distributions, with weights determined by a processing tree structure, and continuous components modeled by parameterized distributions such as Gaussians with separate or shared parameters across states. We discuss identifiability, parameter estimation, model testing, a modeling syntax, and the improved precision of GPT estimates. Finally, a GPT version of the feature comparison model of semantic categorization is applied to computer-mouse trajectories. PMID- 29797179 TI - Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein. AB - In modern medical care in which Kampo and Western drugs are often combined, it is extremely important to clarify drug-drug interaction (DDI) to ensure safety and efficacy. However, there is little evidence of DDI in Kampo medicines. Therefore, as part of our studies to clarify the DDI risk for Kampo medicines, we evaluated the effects of five Kampo medicines [yokukansan (YKS), rikkunshito (RKT), shakuyakukanzoto (SKT), hangeshashinto (HST), and goshajinkigan (GJG)] that are widely used in Japan, on drug transporter P-glycoprotein (P-gp) using a Caco-2 permeability assay. These Kampo medicines inhibited the P-gp transport of digoxin through a Caco-2 cell monolayer. The IC50 values were 1.94-10.80 mg/ml. Of the five Kampo medicines, YKS showed the strongest inhibition (IC50 = 1.94 mg/ml), which was attributed to Uncariae Uncis Cum Ramulus. Unfortunately, we could not find the active ingredients responsible for its action. Finally, the Igut/IC50 values for the five Kampo medicines were calculated, and the DDI risk was objectively evaluated according to the criteria in the DDI guidance issued by the Japanese Ministry of Health, Labor, and Welfare and the US Food and Drug Administration. The Igut/IC50 values for the five Kampo medicines were <=3.4. As these values were <10, they were evaluated as having a weak P-gp inhibitory effect that does not require further verification in humans, suggesting that the DDI risk due to P-gp inhibition for these Kampo medicines is low. The results should provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines. PMID- 29797182 TI - The impact of multi-walled carbon nanotubes (MWCNTs) on macrophages: contribution of MWCNT characteristics. AB - Multi-walled carbon nanotubes (MWCNTs) have wide application prospects but also exhibit notable biotoxicity that is tightly associated with macrophages. Macrophages simultaneously act as initiators and defenders in MWCNT-induced organ lesions, and targeting macrophages with MWCNTs may be a potential immunotherapy and oncotherapy approach. This review focuses on the impacts of MWCNTs on macrophages and further discusses the influence of MWCNT characteristics on their bioactivity. Based on existing studies, MWCNTs stimulate macrophage migration, induce secretion of various cytokines and activate inflammatory pathways in macrophages, especially NLRP3-mediated IL-1beta production. This inflammatory state, together with the oxidative stress and cell membrane lesions induced by MWCNTs, contributes to decreased phagocytic ability and cell viability, which finally results in cell apoptosis and necrosis. A series of intracellular and systemic components, such as toll-like receptor, high-mobility group box 1, Rho associated kinases, scavenger receptor and complement components, may be involved in the above-mentioned cell-MWCNT interactions. The characteristics of MWCNTs can influence their bioactivity in macrophages both mechanically and chemically. The size (length and/or diameter), functionalization, purification and even the experimental method can affect the influence of MWCNTs on macrophages, and a better understanding of these MWCNT characteristics may benefit utilization of this nanomaterial in associated nanomedical applications. PMID- 29797180 TI - Pre- and early postoperative GFAP serum levels in glioma and brain metastases. AB - SUBJECT: To date there is no established tumor marker for the clinical follow-up of glioblastoma, WHO grade IV, (GBM) which constitutes the most frequent and malignant primary brain tumor. However, since there is promising data that the serum glial fibrillary acidic protein (sGFAP) may serve as a biomarker for glial brain tumors, this prospective study aimed at evaluating the diagnostic relevance of perioperative changes in sGFAP levels for the assessment of residual glial tumor tissue in patients undergoing surgery of intracerebral tumors. METHODS: Serum GFAP was measured using an electrochemiluminometric immunoassay (ElecsysR GFAP prototype test, Roche Diagnostics, Penzberg/Germany) in 32 prospectively recruited patients between September 2009 and August 2010. Twenty-five were diagnosed with glioma and seven with brain metastases (BM). We assessed sGFAP levels prior to and at different time points during the early postoperative phase until patient discharge. RESULTS: There were only significant differences in the pre-operative sGFAP levels of patients with gliomas compared to BM (0.18 vs. 0.08 ug/l; p = 0.0198, Welch's t-Test). Even though there was an increase of sGFAP after surgery, there were no significant differences between glioma and BM patients at any other time point. Peak sGFAP levels where reached on postoperative day 1 followed by a slight decrease, but not reaching pre-operative levels until postop day 7. There was no significant correlation between postoperative glioma tumor volume and sGFAP levels in univariate analyses. CONCLUSION: According to our data sGFAP does not appear to be suitable to detect residual glioma tissue in the acute postoperative phase. PMID- 29797184 TI - Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance. AB - The accumulation of excess intracellular or extracellular amyloid beta (Abeta) is one of the key pathological events in Alzheimer's disease (AD). Abeta is generated from the cleavage of amyloid precursor protein (APP) by beta secretase 1 (BACE1) and gamma secretase (gamma-secretase) within the cells. The endocytic trafficking of APP facilitates amyloidogenesis while at the cell surface, APP is predominantly processed in a non-amyloidogenic manner. Several adaptor proteins bind to both APP and BACE1, regulating their trafficking and recycling along the secretory and endocytic pathways. The phosphorylation of APP at Thr668 and BACE1 at Ser498, also influence their trafficking. Neurotrophins and proneurotrophins also influence APP trafficking through their receptors. In this review, we describe the molecular trafficking pathways of APP and BACE1 that lead to Abeta generation, the involvement of different signaling molecules or adaptor proteins regulating APP and BACE1 subcellular localization. We have also discussed how neurotrophins could modulate amyloidogenesis through their receptors. PMID- 29797181 TI - Tumor-related epilepsy: epidemiology, pathogenesis and management. AB - INTRODUCTION: Seizure is a common comorbidity in patients with brain tumor. It may be the presenting symptom or develop after the tumor diagnosis. The underlying pathophysiology of brain tumor-related epilepsy remains poorly understood. METHODS: A comprehensive literature review of Pubmed English articles from 1980-2017 was performed to summarize current knowledge and treatment options of brain tumor-related epilepsy. RESULTS: Multiple factors have been found to contribute to tumor-related epilepsy, including tumor type, speed of tumor growth, location, and tumor burden. The underlying pathogenesis of epilepsy is not clear but perturbations in the peri-tumoral regions, both structural and cellular communications, have been implicated. CONCLUSIONS: Surgical and medical treatments of tumor-related epilepsy remain challenging as additional factors such as the extent of surgical resection, interactions with tumor-related oncological treatments and anti-epileptic medication related side effects need to be considered. PMID- 29797183 TI - Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron. AB - While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A1-dopamine D1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D1 receptor-mediated signaling. A1-D1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome. PMID- 29797185 TI - Are Tanycytes the Missing Link Between Type 2 Diabetes and Alzheimer's Disease? AB - Tanycytes are highly specialized bipolar ependymal cells that line the ventrolateral wall and the floor of the third ventricle in the brain and form a blood-cerebrospinal fluid barrier at the level of the median eminence. They play a pivotal role in regulating metabolic networks that control body weight and energy homeostasis. Due to the glucosensing function of tanycytes, they could be considered as a critical player in the pathogenesis of type 2 diabetes. Genetic fate mapping studies have established the role of tanycytes for the newly detected adult hypothalamic neurogenesis with important implications for metabolism as well as pathophysiology of various neurodegenerative diseases. We believe that a comprehensive understanding of the physiological mechanisms underlying their neuroplasticity, glucosensing, and cross talk with endothelial cells will enable us to achieve metabolic homeostasis in type 2 diabetes patients and possibly delay the progression of Alzheimer's disease and hopefully improve cognitive function. PMID- 29797186 TI - Cost Effectiveness of Secukinumab for the Treatment of Active Ankylosing Spondylitis in the UK. AB - OBJECTIVE: To determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active ankylosing spondylitis (AS) who have not responded adequately to previous treatment with conventional care (CC; biologic-naive population) or previous biologic therapy (biologic-experienced population). PERSPECTIVE AND SETTING: UK National Health Service (NHS). METHODS: The model was structured as a 3-month decision tree leading into a Markov model. Comparators were licensed tumour necrosis factor inhibitors (including available biosimilars) and CC in the biologic-naive and biologic-experienced populations, respectively. Clinical parameters captured treatment response, short-term disease activity and patient functioning, as well as long-term structural disease progression. Utilities were derived from secukinumab trial data. List prices were used for all drugs. The cost year was 2017 and costs and outcomes were discounted at 3.5%. RESULTS: In the biologic naive population, secukinumab dominated adalimumab and certolizumab pegol. Incremental cost-effectiveness ratios (ICERs) versus other comparators were either below L10,000 per quality-adjusted life-year (QALY) gained or south-west ICERs that implied cost effectiveness of secukinumab. In biologic-experienced patients, the ICER for secukinumab versus CC was L4927 per QALY gained. Treatment response rates, short-term treatment effects, long-term radiographic progression and biologic acquisition costs were key model drivers. Scenario analysis found results to be robust to changes in model structural assumptions. Probabilistic analysis identified greater uncertainty in results in the biologic-naive population. CONCLUSIONS: Even at list price, secukinumab appears to represent a cost-effective use of NHS resources for biologic-naive and biologic-experienced patients with active AS. Further research on long-term radiographic progression outcomes would be valuable for future cost-effectiveness analyses in AS. PMID- 29797187 TI - Cost Effectiveness of Secukinumab for the Treatment of Active Psoriatic Arthritis in the UK. AB - OBJECTIVE: The aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naive and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). PERSPECTIVE AND SETTING: The study took the perspective and setting of the UK National Health Service (NHS). METHODS: The model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs). RESULTS: The ICER for secukinumab 150 mg versus SoC was L28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of L5680 per QALY gained versus adalimumab and > L1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between L20,000 and L30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential. CONCLUSIONS: Secukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs. PMID- 29797188 TI - A detection dog for obstructive sleep apnea. AB - PURPOSE: We sought to assess whether a dog can be trained to distinguish obstructive sleep apnea patients from healthy controls based on the olfactory detection of urine. METHODS: Urine samples were collected from 23 adult male obstructive sleep apnea patients and from 20 voluntary adult male volunteers. Three dogs were trained through reinforced operant conditioning. RESULTS: Two of the three dogs correctly detected two thirds of obstructive sleep apnea patients (p < 0.000194 and p < 0.000003, respectively). CONCLUSIONS: We found that dogs can be trained to distinguish obstructive sleep apnea patients from healthy controls based on the smell of urine. Potentially, dogs could be utilized to identify novel biomarkers or possibly screen for obstructive sleep apnea. PMID- 29797189 TI - CRISPR/Cas9 editing of carotenoid genes in tomato. AB - CRISPR/Cas9 technology is rapidly spreading as genome editing system in crop breeding. The efficacy of CRISPR/Cas9 in tomato was tested on Psy1 and CrtR-b2, two key genes of carotenoid biosynthesis. Carotenoids are plant secondary metabolites that must be present in the diet of higher animals because they exert irreplaceable functions in important physiological processes. Psy1 and CrtR-b2 were chosen because their impairment is easily detectable as a change of fruit or flower color. Two CRISPR/Cas9 constructs were designed to target neighboring sequences on the first exon of each gene. Thirty-four out of forty-nine (69%) transformed plants showed the expected loss-of-function phenotypes due to the editing of both alleles of a locus. However, by including the seven plants edited only at one of the two homologs and showing a normal phenotype, the editing rate reaches the 84%. Although none chimeric phenotype was observed, the cloning of target region amplified fragments revealed that in the 40% of analyzed DNA samples were present more than two alleles. As concerning the type of mutation, it was possible to identify 34 new different alleles across the four transformation experiments. The sequence characterization of the CRISPR/Cas9 induced mutations showed that the most frequent repair errors were the insertion and the deletion of one base. The results of this study prove that the CRISPRCas9 system can be an efficient and quick method for the generation of useful mutations in tomato to be implemented in breeding programs. PMID- 29797190 TI - Synthesis and Supercapacitor Performance of Polyaniline/Nitrogen-Doped Ordered Mesoporous Carbon Composites. AB - The electrochemical property of ordered mesoporous carbon (OMC) can be changed significantly due to the incorporating of electron-donating heteroatoms into OMC. Here, we demonstrate the successful fabrication of nitrogen-doped ordered mesoporous carbon (NOMC) materials to be used as carbon substrates for loading polyaniline (PANI) by in situ polymerization. Compared with NOMC, the PANI/NOMC prepared with a different mass ratio of PANI and NOMC exhibits remarkably higher electrochemical specific capacitance. In a typical three-electrode configuration, the hybrid has a specific capacitance about 276.1 F/g at 0.2 A/g with a specific energy density about 38.4 Wh/kg. What is more, the energy density decreases very slowly with power density increasing, which is a different phenomenon from other reports. PANI/NOMC materials exhibit good rate performance and long cycle stability in alkaline electrolyte (~ 80% after 5000 cycles). The fabrication of PANI/NOMC with enhanced electrochemical properties provides a feasible route for promoting its applications in supercapacitors. PMID- 29797191 TI - Anthropogenic activities impact on atmospheric environmental quality in a gas flaring community: application of fuzzy logic modelling concept. AB - We present a modelling concept for evaluating the impacts of anthropogenic activities suspected to be from gas flaring on the quality of the atmosphere using domestic roof-harvested rainwater (DRHRW) as indicator. We analysed seven metals (Cu, Cd, Pb, Zn, Fe, Ca, and Mg) and six water quality parameters (acidity, PO43-, SO42-, NO3-, Cl-, and pH). These were used as input parameters in 12 sampling points from gas-flaring environments (Port Harcourt, Nigeria) using Ibadan as reference. We formulated the results of these input parameters into membership function fuzzy matrices based on four degrees of impact: extremely high, high, medium, and low, using regulatory limits as criteria. We generated indices that classified the degree of anthropogenic activity impact on the sites from the product membership function matrices and weight matrices, with investigated (gas-flaring) environment as between medium and high impact compared to those from reference (residential) environment that was classified as between low and medium impact. Major contaminants of concern found in the harvested rainwater were Pb and Cd. There is also the urgent need to stop gas-flaring activities in Port Harcourt area in particular and Niger Delta region of Nigeria in general, so as to minimise the untold health hazard that people living in the area are currently faced with. The fuzzy methodology presented has also indicated that the water cannot safely support potable uses and should not be consumed without purification due to the impact of anthropogenic activities in the area but may be useful for other domestic purposes. PMID- 29797192 TI - Trapping fresh sea breeze in desert? Health status of Camanchaca, Atacama's fog. AB - Water fog composition was investigated at a fog harvesting installation in the coast of Atacama (North Chile). Chanaral is historically affected by mining contamination discharges. Hydro-chemical characterization of fog water from top of the mountain (where capture installation is located) and at the bottom of the mountain (after vertical transportation where an aquaponic system is located) revealed many compositional differences that compromise the use of water. High acidity and high concentrations in Cu and As in water collected on top of the mountain were found; meanwhile, acidity and Cu decreased, and As levels overpassed the drinking water standards after the vertical transportation. Collected data was assessed according to national and international regulatory standards, neutralization factors (NF), sodium adsorption ratio (SAR), and ion ratios to determine origin of contamination and suitability of destined for human consumption, irrigation, or aquaculture purposes. PMID- 29797193 TI - Associations between maternal exposure to air pollution and birth outcomes: a retrospective cohort study in Taizhou, China. AB - Previous studies from Western country settings had shown correlation between maternal exposure to air pollution and pregnancy outcomes; however, the evidence is difficult to clearly interpret. We aimed to investigate the association of maternal exposure to air pollution expressed as particulate matter (PM2.5, PM10) and nitrogen dioxide (NO2). The exposure was assessed for the 1st, 2nd, and 3rd trimester and related to the birth outcomes. During each trimester of gestation, the effect of PM2.5, PM10, and NO2 exposure as well as the entire pregnancy on the preterm birth, low birth weight, and term babies' birth weight was explored. The dataset of 26,998 delivered live births between January 1, 2013 and May 31, 2016, were collected from the Taizhou Maternal and Child Care Service Center. Air monitoring data were collected from the Taizhou Municipal Environmental Monitoring Center for the same period. We used multi-variable logistic and linear regression analyses to investigate the correlation of air pollution to maternal and outcomes of birth. In models of adjusted single pollutant for second trimester, NO2 concentration was positively correlated with term low birth weight and preterm birth [aRR for an interquartile range increase: 1.59 (1.44, 1.75); 1.27 (1.12, 1.44)]; likewise, a 1 MUg/m3 increase in NO2 was correlated with a reduction in birth weight 2.94 g (P < 0.001) in linear models. Each of PM2.5 and PM10 concentration was also associated with preterm birth [aRR for an interquartile range increase 1.30 (1.21, 1.38); 1.39 (1.27, 1.52)]. In co pollutant models, the results were similar. Maternal exposure to air pollutant in Taizhou was associated with an increased risk of preterm birth and reduction in birth weight. We reported a potential link between maternal exposure to air pollution and negative outcomes of birth in Taizhou, China. PMID- 29797195 TI - Unravelling motor behaviour hallmarks in intoxicated adolescents: methylmercury subtoxic-dose exposure and binge ethanol intake paradigm in rats. AB - Methylmercury (MeHg) is a hazardous environmental pollutant, affecting Amazon basin communities by anthropogenic activities. The exact safe level of MeHg exposure is unclear, despite the efforts of health international societies to avoid mercury (Hg) poisoning. Central nervous system is severely impacted by Hg intoxication, reflecting on motor impairment. In addition, alcohol has been associated to an overall brain damage. According to lifestyle of Amazon riverside communities, alcohol intake occurs frequently. Thus, we investigated if continuous MeHg exposure at low doses during adolescence displays motor deficits (experiment 1). In the experiment 2, we examine if the co-intoxication (i.e. MeHg plus ethanol exposure) during adolescence intensify motor damage. In the experiment 1, Wistar adolescent rats (31 days old) received chronic exposure to low dose (CELD) of MeHg (40 MUg/kg/day) for 35 days. For the experiment 2, five sessions of alcohol binge drinking paradigm (3ON-4OFF; 3.0 g/kg/day) were employed associated to MeHg intoxication. Motor behaviour was evaluated by the open field, pole test, beam walking and rotarod paradigms. CELDS of MeHg display motor function damage, related to hypoactivity, bradykinesia-like behaviour, coordination deficits and motor learning impairment. Co-intoxication of MeHg plus ethanol reduced cerebellar Hg content, however also resulted in motor behavioural impairment, as well as additive effects on bradykinesia and fine motor evaluation. PMID- 29797196 TI - Adsorptive removal of phenolic compounds from aqueous solutions using pine cone biomass: kinetics and equilibrium studies. AB - In this study, a novel inexpensive biosorbent of pine cone powder was used for the treatment of wastewater contaminated with phenol and chlorophenols (CPhs). The biosorbent was thoroughly characterized by using CHN and BET measurements, as well as FTIR, SEM, and XRD analyses. Kinetic and equilibrium biosorption experiments showed that the uptake was more than 80% within the first 30 min of contact time at pH 5.0. The biosorption of 4-CPh onto pine cone powder was higher than those of phenol and 2-CPh. The kinetic data were consistent with the pseudo first-order kinetic model, and the Langmuir isotherm model best represented the equilibrium data. The maximum biosorption capacities of phenol, 2-CPh, and 4-CPh were 164.51, 189.44, and 220.12 mg/g, respectively, at 30 +/- 1 degrees C. Therefore, the pine cone powder is an effective low-cost adsorbent for the removal of phenol and CPhs from the contaminated water. PMID- 29797194 TI - Erythrocyte acetylcholinesterase as biomarker of pesticide exposure: new and forgotten insights. AB - Acetylcholinesterase (AChE) acts on the hydrolysis of acetylcholine, rapidly removing this neurotransmitter at cholinergic synapses and neuromuscular junctions as well as in neuronal growth and differentiation, modulation of cell adhesion ("electrotactins") and aryl-acylamidase activity (AAA). This enzyme is also found in erythrocyte, as 160 kDa dimer that anchors to the plasma membrane via glycophosphatidylinositol. The function of this enzyme in erythrocytes has not yet been elucidated; however, it is suspected to participate in cell-to-cell interactions. Here, a review on erythrocyte AChE characteristics and use as biomarker for organophosphorus and carbamate insecticides is presented since it is the first specific target/barrier of the action of these pesticides, besides plasma butyrylcholinesterase (BChE). However, some past and current methods have disadvantages: (a) not discriminating the activities of AChE and BChE; (b) low accuracy due to interference of hemoglobin in whole blood samples. On the other hand, extraction methods of hemoglobin-free erythrocyte AChE allows: (a) the freezing and transporting of samples; (b) samples free of colorimetric interference; (c) data from only erythrocyte AChE activity; (d) erythrocyte AChE specific activity presents higher correlation with the central nervous system AChE than other peripheral ChEs; (e) slow spontaneous regeneration against anti ChEs agents of AChE in comparison to BChE, thus increasing the chances of detecting such compounds following longer interval after exposure. As monitoring perspectives, hemoglobin-free methodologies may be promising alternatives to assess the degree of exposure since they are not influenced by this interfering agent. PMID- 29797197 TI - The content of essential and toxic elements in the hair of the mane of the trotter horses depending on their speed. AB - A study on the Russian trotting breeds was conducted to assess the impact of horses' sporting results and the degree of accumulation of chemical elements in the hair. In the first phase of the research, the elemental composition of the mane hair of trotter horses (n = 215) was studied. Based on these studies, percentile intervals for the distribution of concentrations of chemical elements in the hair have been established, and the values of 25 and 75 percentile adopted as a "physiological standard" have been defined. In the second stage of the research into clinically healthy Russian trotting breeds (n = 56), it was estimated that the sporting results were dependent on the elemental status defined by the hair. The elemental composition of the hair was defined by 25 chemical elements using atomic emission and mass spectrometry. It is established that the mane hair is closely related to the sporting results of trotter horses. Thus, in animal wool with the highest sporting achievements, there were reliably less I, Cr, Co, Li, V, Al, Pb, and Cd, and reliably more Si than the low ones. Differences in individual elements exceeded 200%. As sporting performance diminished, the number of elements within the standard increased. For example, for mares with average speed, there were deviations from the physiological standard by 6 elements (P, Fe, Mn, I, Co, Si), with the low one by 13 elements (P, Fe, Cu, Mn, I, Co, Si, K, Cr, Ni, V, Al, Pb). A comparative estimate of the mineralization of the horses' mane measured by the sum of the amount of substances showed that there was a negative correlation between the accumulation of toxic elements and the speed (r = - 0.59). On the basis of the above, a conclusion is reached on the future use of the mane hair to assess the speed qualities of trotter horses. PMID- 29797198 TI - Optimization of operating conditions for the valorization of olive mill wastewater using membrane processes. AB - The main goal of this work was to assess the performance of an integrated membrane system for the treatment and valorization of wastewater generated from an olive mill (OMW) coming from a traditional extraction press. Two different lots of this effluent were firstly processed in an ultrafiltration (UF) pilot unit after a pretreatment by screening. The effect of transmembrane pressure (TMP) and temperature on the chemical oxygen demand (COD) reduction and removal of total phenolic (TPh) content was investigated. Under optimal conditions (TMP = 1.5 bar and T = 20 degrees C), 20.6 and 26.8% for COD and TPh removal were achieved, respectively. The permeate from UF was then treated by nanofiltration (NF) in order to obtain a retentate enriched in phenolic compounds. The influence of pressure drop (DeltaP), temperature, and pH on the removal of COD, TPh, and permeate flow was examined using a 23 full-factorial experimental design. The effect of the independent variables and their interactions on the process performance was analyzed with Pareto charts. Multivariable regression models allowed to built 3D surface plots. The best conditions that maximize the COD abatement (83.3%) and TPh removal (93.1%) were DeltaP = 18 bar, T = 20 degrees C, and a pH 2.7. It can be concluded that the integration of UF and NF processes investigated in this work is a promising strategy for the treatment and valorization of OMW. PMID- 29797199 TI - Removal of Cs+ from aqueous solutions by perlite. AB - Perlite is an abundant mineral that requires minimum processing before use either as raw or expanded perlite, resulting in a low-cost, natural porous material. The application of materials for the removal of radioactive cesium from liquid effluents and contaminated waters is currently of great interest. Perlite has been evaluated in the last years for the sorption of a variety of metals, but it had not been investigated before for removal of Cs+ from contaminated waters. The present work examines the use of perlites from a deposit in Salta, Argentina, for removal of Cs+ from aqueous solutions. The mineral was characterized by means of powder X-ray diffraction, thermal analysis, analysis of specific area, and scanning electron microscopy. The effect of solution pH, presence of concomitant ions, contact time, Cs+ initial concentration, perlite dose, and basic or acidic treatment of the sorbent were studied by batch experiments. Removal increased at high pHs and after treatment with NaOH. Sorption of Cs+ by perlite presented a rapid rise in the first 80 min of contact. The selected material (from Pava mine) yielded removal efficiencies of 84 and 89% before and after treatment with NaOH, respectively, for a dose of 30 g perlite/L and initial cation concentration of 10 mg/L. Our results demonstrate that perlite is a material capable of removing Cs+ from aqueous solutions, even when applied at low doses. These findings are relevant in the context of removal of radioactive Cs isotopes from nuclear effluents and in case of contamination of environmental waters. PMID- 29797200 TI - The invisible hand and EKC hypothesis: what are the drivers of environmental degradation and pollution in Africa? AB - This study examined the drivers of environmental degradation and pollution in 17 countries in Africa from 1971 to 2013. The empirical study was analyzed with Westerlund error-correction model and panel cointegration tests with 1000 bootstrapping samples, U-shape test, fixed and random effect estimators, and panel causality test. The investigation of the nexus between environmental pollution economic growth in Africa confirms the validity of the EKC hypothesis in Africa at a turning point of US$ 5702 GDP per capita. However, the nexus between environmental degradation and economic growth reveals a U shape at a lower bound GDP of US$ 101/capita and upper bound GDP of US$ 8050/capita, at a turning point of US$ 7958 GDP per capita, confirming the scale effect hypothesis. The empirical findings revealed that energy consumption, food production, economic growth, permanent crop, agricultural land, birth rate, and fertility rate play a major role in environmental degradation and pollution in Africa, thus supporting the global indicators for achieving the sustainable development goals by 2030. PMID- 29797201 TI - Phosphorous-doped TiO2 nanoparticles: synthesis, characterization, and visible photocatalytic evaluation on sulfamethazine degradation. AB - Mesoporous phosphorous-doped TiO2 (TP) with different wt% of P (0.5, 1.0, and 1.5) was synthetized by microwave-assisted sol-gel method. The obtained materials were characterized by XRD with cell parameters refinement approach, Raman, BET specific surface area analysis, SEM, ICP-OES, UV-Vis with diffuse reflectance, photoluminescence, FTIR, and XPS. The photocatalytic activity under visible light was evaluated on the degradation of sulfamethazine (SMTZ) at pH 8. The characterization of the phosphorous materials (TP) showed that incorporation of P in the lattice of TiO2 stabilizes the anatase crystalline phase, even increasing the annealing temperature. The mesoporous P-doped materials showed higher surface area and lower average crystallite size, band gap, and particle size; besides, more intense bands attributed to O-H bond were observed by FTIR analysis compared with bare TiO2. The P was substitutionally incorporated in the TiO2 lattice network as P5+ replacing Ti4+ to form Ti-O-P bonds and additionally present as PO43- on the TiO2 surface. All these characteristics explain the observed superior photocatalytic activity on degradation (100%) and mineralization (32%) of SMTZ under visible radiation by TP catalysts, especially for P-doped TiO2 1.0 wt% calcined at 450 degrees C (TP1.0-450). Ammonium, nitrate, and sulfate ions released during the photocatalytic degradation were quantified by ion chromatography; the nitrogen and sulfur mass balance evidenced the partial mineralization of this recalcitrant molecule. PMID- 29797203 TI - Total sediment transport from an urbanizing watershed in the upper Yellow River, China. AB - For many event-based, high-sediment yield rivers draining arid zones, where erosion activities in the watershed and fluvial erosion in the stream channel are nearly equally important in sediment transport, determination of fluvial sediment dynamics are of great importance in establishing reliable strategies to manage environmental changes in watershed scale. Wash load rating curve indicating watershed characteristic changes and Ackers and White's bed load function (wash load excluded) used for determining bed load transport dynamics are distinguished for the first time to recognize the true sediment transport mode in the lower Huangshui River, which is the largest tributary of the upper Yellow River, contributing a lot to the wash load of the Inner Mongolia desert reach of the Yellow River and causing complicated water-sediment response. Based on the continuous and detailed hydrological data monitored at the Minhe gauge station, our results indicated that the sediment transport regime has altered since the 1980s in response to the eco-environmental changes mainly due to urbanization, with suspended sediment concentration (SSC) decreased by 50% on average compared with the natural state (1950-1980). The combined use of wash load rating curve and theoretical bed load function derived an estimate of total sediment transport due to comprehensive ecological management since the 2000s to be 3.43 * 107 t for the lower Huangshui River, among which the total bed load is 1.40 * 107 t, and the wash load is 2.03 * 107 t. The transport ratio of wash load to total bed load is 1.45:1. PMID- 29797204 TI - Experimental analysis of performance and emission on DI diesel engine fueled with diesel-palm kernel methyl ester-triacetin blends: a Taguchi fuzzy-based optimization. AB - The energy situation and the concerns about global warming nowadays have ignited research interest in non-conventional and alternative fuel resources to decrease the emission and the continuous dependency on fossil fuels, particularly for various sectors like power generation, transportation, and agriculture. In the present work, the research is focused on evaluating the performance, emission characteristics, and combustion of biodiesel such as palm kernel methyl ester with the addition of diesel additive "triacetin" in it. A timed manifold injection (TMI) system was taken up to examine the influence of durations of several blends induced on the emission and performance characteristics as compared to normal diesel operation. This experimental study shows better performance and releases less emission as compared with mineral diesel and in turn, indicates that high performance and low emission is promising in PKME triacetin fuel operation. This analysis also attempts to describe the application of the fuzzy logic-based Taguchi analysis to optimize the emission and performance parameters. PMID- 29797202 TI - Global development of the studies focused on antibiotics in aquatic systems from 1945 to 2017. AB - Antibiotics are used to fight diseases in humans and farm animals. Their residues, however, can enter aquatic environments and affect the resistance of non-target microbial strains, and the prevalence of antibiotic resistance genes (ARGs) potentially poses negative impacts on human health. In order to better understand how the studies of antibiotics have been conducted, we analyzed the publications on antibiotics in aquatic systems for the period of 1945-2017. We applied a bibliometric analysis method by coupling cluster analysis and network analysis. Results indicated that early research on antibiotics in water was mostly performed in America and Europe, while, in recent years, publications for the same subject were dominated by China and the USA. The majority of the articles were published in journal Chemosphere and the most representative subject categories of the seven sections were "Environmental science and ecology," "Chemistry," "Engineering," "Biochemistry and molecular biology," "Water resources," "Agriculture," and "Pharmacology and pharmacy." The most studied class of antibiotics was tetracyclines in wastewater. Antibiotic resistance, ARGs, Escherichia coli, and some mechanistic studies such as adsorption, toxicity, degradation, and kinetics were common topics in this field. ARGs present a major public health concern and much attention should be directed at the problems with antibiotics in the future studies of water. PMID- 29797205 TI - Pretreated animal and human waste as a substantial nutrient source for cultivation of microalgae for biodiesel production. AB - The use of human and animal wastes for fertilization of aquaculture ponds has been practiced for thousands of years. In the present work, we have used the excreta (human urine, poultry waste, cow dung, and urine) as a nutrient source for the cultivation of Chlorella singularis, Micractinium pusillum, and Chlorella sorokiniana strains of microalgae. Different solid wastes were treated with 60 mM H2SO4 for the extraction of nutrients. After treatment, the supernatant of different solid wastes and liquid waste were diluted 5, 10, 15, and 20% to be used as a media for the cultivation of microalgae. Chlorella sorokiniana was able to grow in all concentration of excreta media. The maximum growth rate 140 +/- 3.1 mg/L/day and lipid production (45.5 +/- 2.3 mg/L/day) was obtained in 20% poultry. Among the different excreta media used for cultivation of microalgae, poultry media displayed the best results and thus, should be used for large scale cultivation of microalgae. PMID- 29797206 TI - Trivalent Chromium Supplementation Ameliorates Oleic Acid-Induced Hepatic Steatosis in Mice. AB - Trivalent chromium [Cr(III)] is recognized as an essential trace element for human health, whereas its effect on hepatic lipid metabolism has not yet been fully understood. This study aimed to investigate the beneficial effects and potential mechanisms of Cr(III) on hepatic steatosis in an oleic acid (OA) induced mice model. Mice were fed with high OA for 12 weeks to induce lipid accumulation, and co-administrated with Cr(III) supplementation. Indexes of liver lipid accumulation, associated lipid genes expression, fatty acids (FAs) profile and inflammatory cytokines were analyzed. The data showed that Cr(III) supplementation could attenuate disease progress of hepatic steatosis and protect liver from high OA. After Cr(III) supplementation, elevated body weight and liver injury in steatosis mice were reversed, excessive lipid accumulation and FAs were also reduced. The up-regulation of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2) following steatosis induction were inhibited by Cr(III). Cr(III) reduced the content of pro-inflammatory cytokines (IL-1beta and TNF-alpha, IL-12) and restored the level of anti-inflammatory cytokine (IL-10) to the control values. Our results suggest that Cr(III) supplementation is a novel strategy for alleviating OA-induced hepatic steatosis. PMID- 29797207 TI - Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation. AB - In our previous study, chromium malate is beneficial for type 2 diabetic rats in control glycometabolism and lipid metabolism. The present study was designed to observe the chronic toxicity, lipid metabolism, learning and memory ability, and related enzymes of chromium malate in rats during the year. The results showed that pathological, toxic, feces, and urine of chromium malate (at daily doses of 10.0, 15.0, and 20.0 MUg Cr/kg bm) did not change measurably. Chromium malate (at daily doses of 15.0 and 20.0 MUg Cr/kg bm) could significantly reduce the levels of total cholesterol (TC), LDL, and triglyceride (TG), and increase the level of HDL in male rats compared to control group and chromium picolinate group. Significant escalating trends of the escape latency and swimming speed (Morris water maze test), and the original platform quadrant stops, residence time, and swimming speed (Space exploration test) in male rats of chromium malate groups were obtained. The SOD, GSH-Px, and TChE activities of chromium malate (at daily doses of 15.0 and 20.0 MUg Cr/kg bm) were enhanced significantly in male rats compared with those of the normal control group and chromium picolinate group. Glycometabolism and related enzymes had no significant changes compared to normal control group and chromium picolinate group. These results indicated that long term chromium malate supplementation did not cause measurable toxicity at daily doses of 10.0, 15.0, and 20.0 MUg Cr/kg bm and could improve dyslipidemia and learning and memory deficits. PMID- 29797208 TI - Safety and effectiveness of direct oral anticoagulants following ultrasound assisted catheter directed thrombolysis for venous thromboembolism. AB - Ultrasound-assisted catheter-directed thrombolysis (USAT) is a novel approach for the treatment of venous thromboembolism (VTE) that is thought to be associated with a decreased risk of bleeding. Direct oral anticoagulants (DOACs) are approved for the treatment of VTE but have not been studied in a post fibrinolysis setting. The intention of this retrospective observational study was to determine the safety and effectiveness of DOACs compared to the vitamin-K antagonist (VKA) warfarin following USAT in patients with documented VTE. Included patients were aged 18 years or older who had documented VTE and received oral anticoagulation with either a DOAC or VKA following USAT. The primary outcome of this study was to compare the 90-day composite incidence of major and minor bleeding and recurrent VTE between patients receiving DOACs after USAT to those receiving VKA after USAT. Similar rates of bleeding and recurrent VTE were observed (4/42; 9.5% in the DOAC group versus 2/34; 5.9% in the VKA group). The use of DOAC therapy post-USAT for VTE was not associated with higher rates of 90 day major or minor bleeding or 90-day recurrent VTE. PMID- 29797209 TI - The Superoxide Dismutase Mimetic TEMPOL and Its Effect on Retinal Ganglion Cells in Experimental Methanol-Intoxicated Rats. AB - INTRODUCTION: The incidence of blindness due to methanol intoxication is higher in males of productive age. The management of methanol-induced toxic optic neuropathy is yet to produce satisfactory results. Antioxidant therapy is now used as an alternative method of preventing methanol intoxication. The aim of this study was to observe the effect of TEMPOL (4-hydroxy-2,2,6,6 tetramethylpiperidinyl-1-oxyl), a superoxide dismutase (SOD) mimetic, on retinal ganglion cells in methanol-intoxicated rats. METHODS: This experimental study was conducted with 20 male Wistar rats that were 10-12 weeks old and weighed 300-350 g. The rats were divided into four groups that each received a different treatment: a negative control group, a positive control group, a methanol group, and a methanol + TEMPOL group. Enucleated eyes from all groups were sliced and stained using hematoxylin-eosin (HE). Retinal layer and ganglion cells were assessed based on cellular structure, cellular swelling, and vacuole formation in the ganglion cell layer as observed at * 200 magnification. The Kruskal-Wallis test and the Mann-Whitney test were used, with significance taken to correspond to p < 0.05. RESULTS: Retinal ganglion cells of the control group had fewer vacuoles and a more well-organized cellular structure compared to those of the methanol group. The histopathologic scores of the methanol-intoxicated group were lower than those of the TEMPOL therapy group; p = 0.011 (i.e., p < 0.05). CONCLUSIONS: TEMPOL had a positive impact on the cellular structure of retinal ganglion cells in methanol-intoxicated rats. PMID- 29797210 TI - Colorimetric Analysis of Hibiscus Beverages and their Potential Antioxidant Properties. AB - In food industry, roselle beverages and their subproducts could be functional ingredients since they are an excellent source of bioactive compounds with improved performance due to their important anthocyanins content. The aim of this study was to analyze anthocyanin content and antioxidant properties of aqueous infusions elaborated with color contrasting Hibiscus materials and design a mathematical model in order to predict color-composition relationship. Color measurements of beverages from roselle (Negra, Sudan and Rosa) were made by transmission spectrophotometry, anthocyanins quantification was determined by HPLC, and antioxidant potential was evaluated by in vitro methods (ABTS and FRAP assays). Beverages prepared with particle size minor of 250 MUm presented until 4 and 2- times more anthocyanins content and antioxidant capacity respectively, in comparison to beverages prepared with powders with particle size major of 750 MUm. Positive correlations among pigments composition and color parameters were found (p < 0.05), showing that anthocyanins content, antioxidant capacity, C*ab and hab values increased in relation with the smallest particle size of flours. Also, mathematical models were stablished to predict anthocyanin content (r >= 0.97) and antioxidant capacity (r >= 0.89) from color data; we propose equations for quick estimation of the antioxidant capacity in the Hibiscus beverages with high anthocyanin content. The obtained models could be an important tool to be used in food industry for pigment characterization or functional compounds with potential health benefits. PMID- 29797211 TI - Use of 99mTc-sestamibi SPECT/CT when conventional imaging studies are negative for localizing suspected recurrence in differentiated thyroid cancer: a method and a lesson for clinical management. AB - PURPOSE: The detection of recurrent disease in differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple negative conventional imaging studies can be challenging, especially when 18F-FDG PET/CT scan is also negative. We report a patient and review the literature on the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tg in patients with negative conventional imaging including negative 18F-FDG PET/CT scans. PATIENT AND METHODS: A 73-year-old woman was referred for widely-invasive metastatic follicular thyroid cancer with bone metastasis to her left mandible. She had a total thyroidectomy, left mandibular resection, and 131I therapy of 145 mCi (5.4 GBq) and her subsequent unstimulated serum Tg level was 29 ng/ml (TgAb negative). At six months' follow-up, her stimulated Tg was 527 ng/ml (TSH 188 mIU/L, TgAb negative). All imaging studies performed within the prior 12 months were reported as negative for recurrence or metastasis; this included neck ultrasound, diagnostic radioiodine scan, chest CT and, 18F-FDG PET/CT. The patient was injected with 24.6 mCi (910 MBq) of 99mTc sestamibi intravenously, and whole-body and SPECT/CT images were acquired. RESULTS: The 99mTc-sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponded to an occipital lytic bone lesion on the SPECT/CT. The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic follicular thyroid cancer. Five months post-surgery, the suppressed Tg was markedly reduced and remained stable at ~3.2 ng/ml. With the knowledge of the DTC recurrence location, the two sets of 18F-FDG images were re-evaluated. The more thorough and targeted interpretation underscored the importance of structured image reporting. The current literature on the utility of 99mTc-sestamibi scans when radioiodine, 18F FDG PET/CT, and other imaging studies are negative is sparse and inconsistent. CONCLUSIONS: 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT does not identify the source of elevated Tg levels in DTC. PMID- 29797212 TI - Comparison of subcutaneous insulin aspart and intravenous regular insulin for the treatment of mild and moderate diabetic ketoacidosis in pediatric patients. AB - PURPOSE: To compare the safety/efficacy of intermittent subcutaneous rapid-acting insulin aspart with the standard low-dose intravenous infusion protocol of regular insulin for treatment of pediatric diabetic-ketoacidosis. METHODS: For a prospective randomized-controlled clinical trial on 50 children/adolescents with mild/moderate diabetic-ketoacidosis, the diagnostic criteria for ketoacidosis included: blood glucose level >250 mg/dl, ketonuria>++, venous pH <7.3 and/or bicarbonate <15 mEq/l. DATA COLLECTED: age, sex, clinical/laboratory parameters including blood sugar, arterial blood gases, urine ketones, severity of diabetic ketoacidosis, amount of insulin administered to correct acidosis, time to recover from diabetic-ketoacidosis, number of days of hospitalization, and complications. Patients were randomly assigned to intervention (subcutaneous) and control (intravenous) groups. Controls received 0.05-0.1 unit/kg/hour intravenous regular insulin infusion until resolution of diabetic-ketoacidosis and stayed in the intensive care unit. Interventions received 0.15 unit/kg subcutaneous insulin aspart every two hours and stayed in regular medical ward. RESULTS: From 50 children (age 2-17 years), 56% (28) were females, and 48% (24) had established type I diabetes. Intervention and control groups had similar baseline clinical/laboratory findings. Average age (years) was 8.6 +/- 0.8 for intervention and 8.86 +/- 0.7 for control group (p = 0.4) with 64% having moderate diabetic-ketoacidosis. The mean total-dose of insulin units needed for treatment of diabetic-ketoacidosis in intervention (subcutaneous insulin aspart) was lower than controls (intravenous regular insulin) (p < 0.001). No mortality/serious events happened. Three diabetic-ketoacidosis recurrences among interventions and one among controls occurred. CONCLUSIONS: To manage mild/moderate diabetic-ketoacidosis in children/adolescents, subcutaneous rapid acting insulin aspart is an alternative to intravenous infusion of regular insulin. Subcutaneous insulin treated moderate DKA with faster recovery/shorter hospital stay. PMID- 29797213 TI - Evaluation of melatonin and AFMK levels in women with breast cancer. AB - PURPOSE: Changes in the circadian rhythm may contribute to the development of cancer and are correlated with the high risk of breast cancer (BC) in night workers. Melatonin is a hormone synthesized by the pineal gland at night in the absence of light. Levels of melatonin and the metabolite of oxidative metabolism AFMK (acetyl-N-formyl-5-methoxykynurenamine), are suggested as potential biomarkers of BC risk. The aims of this study were to evaluate levels of melatonin and AFMK in women recently diagnosed with BC, women under adjuvant chemotherapy, and night-shift nurses, and compare them with healthy women to evaluate the relation of these compounds with BC risk. METHODS: Blood samples were collected from 47 women with BC, 9 healthy women, 10 healthy night shift nurses, and 6 patients under adjuvant chemotherapy. Compound levels were measured by mass spectrometry. RESULTS AND CONCLUSIONS: Our results showed that women with BC had lower levels of melatonin compared to control group women, and even lower in night-shift nurses and in patients under adjuvant chemotherapy. There was no significant difference of AFMK levels between the groups. In addition to this, high levels of melatonin and AFMK were related to patients with metastasis, and high levels of AFMK were related to the presence of lymph node-positive, tumor > 20 mm and patients who sleep with light at night. Our results showed a reduction of melatonin levels in BC patients, suggesting a relation with the disease, and in addition, point to the importance of melatonin supplementation in women that work at night to reduce the BC risk. PMID- 29797214 TI - Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. AB - PURPOSE: Epidemiological data are pivotal for the estimation of disease burden in populations. AIM: Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population. METHODS: Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests. RESULTS: At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4-8.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization (>=3 accesses/year, p < 0.001) compared to sex-age matched controls. CONCLUSIONS: This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients' hospitalization. PMID- 29797216 TI - Diuretic renography in hydronephrosis: a retrospective single-center study. AB - PURPOSE: Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis other than transient hydronephrosis. In children with unilateral hydronephrosis, mercaptoacetyltriglycine-3 diuretic renography (MAG3) is used to calculate differential renal function and to assess drainage. The aim of our study is to examine whether anteroposterior pelvic diameter on renal ultrasound (US) scan can predict both differential renal function (DFR) and obstruction in pediatric patients, and whether an US adequately identifies those patients who need further investigation. We also aimed to design a study with a larger sample size than previous studies investigating the relationship between MAG3 and US. METHODS: We retrospectively reviewed the MAG3, US, dimercaptosuccinic acid scan (DMSA) findings, and medical records of pediatric patients with hydronephrosis and/or atrophy who were at follow-up between January 2013 and December 2016 in our center which is located in the south-east region of Turkey. RESULTS: Two hundred and twenty-five pediatric patients (M/F = 156/69) with unilateral hydronephrosis but without VUR were enrolled in this study. The mean age of the children was 45.4 +/- 48.3 months (range 2-173 months). Sixty nine patients had obstructive pattern on 99mTc-MAG3. With respect to obstructive pattern, there was a significant difference between the hydronephrosis groups both with 15 and 20 mm border. An APD of greater than 20 mm had 15.8 times (95% CI 5.72-43.69) higher likelihood of having obstruction MAG3 findings. On the other hand, an APD of greater than 15 cm had 9.2 times (95% CI 3.01-28.57) higher likelihood of having obstruction MAG3 findings. The incidence of urinary tract infections was lower than in the obstructive group than the other groups. The regression analysis showed that an APD of greater than 20 mm was a risk factor for low DRF (OR = 5.208, 95% CI 1.529-17.743, p = 0.008). However, the regression analysis showed that an APD of greater than 15 mm was not a risk factor low DRF. CONCLUSIONS: The combination of ultrasound and MAG3 provides the necessary anatomical and functional information to follow the degree of obstruction and to decide between surgical intervention and conservative follow-up. Our study supports a threshold of 20 mm rather than 15 mm for severe obstruction and a low DRF. An APD threshold greater than 15 mm did not have a predictive value in DRF estimation. PMID- 29797217 TI - Which Complex Patients Should Be Referred for Intensive Care Management? A Mixed Methods Analysis. AB - BACKGROUND: A large and increasing proportion of health care costs are spent caring for a small segment of medically and socially complex patients. To date, it has been difficult to identify which patients are best served by intensive care management. OBJECTIVE: To characterize factors that best identify which complex patients are most suited for intensive care management. DESIGN: We conducted a mixed-methods study involving 35 care managers (CMs; 10 licensed social workers and 25 registered nurses) working in intensive care management programs within Kaiser Permanente Northern California (KPNC) outpatient medical centers. We asked CMs to review a randomly selected list of up to 50 patients referred to them in the prior year and to categorize each patient as either (1) "good candidates" for care management, (2) "not needing" intensive care management, or (3) "needing more" than traditional care management could provide. We then conducted semi-structured interviews to understand how CMs separated patients into these three groups. RESULTS: CMs assigned 1178 patients into the 3 referral categories. Less than two thirds (62%, n = 736) of referred patients were considered good candidates, with 18% (n = 216) categorized as not needing care management and 19% (n = 226) as needing more. Compared to the other two categories, good candidates were older (76.2 years vs. 73.2 for not needing and 69.8 for needing more, p < 0.001), prescribed more medications (p = 0.02) and had more prior year outpatient visits (p = 0.04), while the number of prior year hospital and emergency room admissions were greater than not needing but less than needing more (p < 0.001). A logistic regression model using available electronic record data predicted good candidate designation with a c statistic of 0.75. Several qualitative themes emerged that helped define appropriateness for referral, including availability of social support, patient motivation, non medical transitions, recent trajectory of medical condition, and psychiatric or substance use issues. CONCLUSION: Many apparently complex patients are not good candidates for intensive care management. Current electronic medical records do not capture several of the most salient characteristics that determine appropriateness for care management. Our findings suggest that systematic collection of social support, patient motivation, and recent non-medically related life change information may help identify which complex patients are most likely to benefit from care management. PMID- 29797215 TI - The application of a single-use fiberoptic flexible ureteroscope for the management of upper urinary calculi. AB - OBJECTIVE: To evaluate the clinical outcomes with a Chinese single-use fiberoptic flexible ureteroscope (YouCare Tech) from a prospective database. MATERIALS AND METHODS: A prospective study was conducted in a single center in China between January 2016 and October 2017. All consecutive patients who underwent flexible ureteroscopy performed by YouCare flexible ureteroscope were analyzed. Patients' demographics, clinical characteristics, intraoperative parameters, postoperative complications, and stone-free rate were evaluated and recorded. Stone-free status was defined as no visible stones or clinically insignificant residual stones < 2 mm on a postoperative image study. RESULTS: A total of 684 procedures were performed for 653 patients (31 patients had bilateral stones). A double J stent had been previously placed in 431 patients. The location of the calculi was upper calyx, middle calyx, lower calyx, and renal pelvis and proximal ureter in 74, 101, 211, 115, and 183 patients, respectively. The median operative time was 52 min. The postoperative stone-free rate for the first 2 weeks after surgery was 78.5%, which increased to 91.1% at the first month. The overall stone-free rate was 95.2%. The complication rate was minor and short-term, such as gross hematuria or flank pain. CONCLUSION: YouCare flexible ureteroscope can be considered effective and safe in the treatment of both upper ureteral and renal stones in selected patients. Further evaluation of comparison with other FURS's surgical outcomes and cost-effectiveness analysis will help to present the best utility of this single-use FURS in clinical practice. PMID- 29797218 TI - Chronic Multisymptom Illness Among Iraq/Afghanistan-Deployed US Veterans and Their Healthcare Utilization Within the Veterans Health Administration. PMID- 29797221 TI - Correction to: Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid. AB - The following affiliation should be added to the authors Agostino Chiaravalloti and Orazio Schillaci. PMID- 29797219 TI - Loss of EGFR confers acquired resistance to AZD9291 in an EGFR-mutant non-small cell lung cancer cell line with an epithelial-mesenchymal transition phenotype. AB - PURPOSE: AZD9291 is an irreversible, small-molecule inhibitor which has potency against mutant EGFR- and T790M-resistant mutation. Despite the encouraging efficacy in clinical, the acquired resistance will finally occur. Further study will need to be done to identify the acquired resistance mechanisms and determine the next treatment. METHODS: We established an AZD9291-resistant cell line (HCC827/AZDR) from parental HCC827 cell line through stepwise pulsed selection of AZD9291. The expression of EGFR and its downstream pathways were determined by western blot analysis or immunofluorescence assay. The sensitivity to indicated agents were evaluated by MTS. RESULTS: Compared with parental HCC827 cells, the HCC827/AZDR cells showed high resistance to AZD9291 and other EGFR-TKIs, and exhibited a mesenchymal-like phenotype. Almost complete loss of EGFR expression was observed in HCC827/AZDR cells. But the activation of downstream pathway, MAPK signaling, was found in HCC827/AZDR cells even in the presence of AZD9291. Inhibition of MAPK signaling had no effect on cell viability of HCC827/AZDR and could not reverse AZD9291 resistance because of the subsequent activation of AKT signaling. When treated with the combination of AKT and MAPK inhibitor, HCC827/AZDR showed remarkable growth inhibition. CONCLUSIONS: Loss of EGFR could be proposed as a potential acquired resistance mechanism of AZD9291 in EGFR mutant NSCLC cells with an EMT phenotype. Despite the loss of EGFR, the activation of MAPK pathway which had crosstalk with AKT pathway could maintain the proliferation and survival of resistant cells. Blocking MAPK and AKT signaling may be a potential therapeutic strategy following AZD9291 resistance. PMID- 29797220 TI - Effectiveness and tolerability of targeted drugs for the treatment of metastatic castration-resistant prostate cancer: a network meta-analysis of randomized controlled trials. AB - PURPOSE: Castration-resistant prostate cancer (CRPC) refers to prostate cancer that has progressed after initial androgen deprivation therapy (ADT). Over the years, treatment strategies for metastatic CRPC (mCRPC) have undergone considerable changes. We performed a network meta-analysis to assess the effectiveness and tolerability of targeted agents for mCRPC. METHODS: We search databases including MEDLINE, EMBASE, and the Cochrane Library through Sep 5, 2017. The major effectiveness outcomes were progression-free survival (PFS) and overall survival (OS). The tolerability outcome was severe adverse events (AEs) of grade >= 3. RESULTS: Twenty-six articles assessing a total of 20,314 patients were included in this study. A random-effect analysis showed that targeted agents could significant prolong PFS in mCRPC patients (I2 = 94.3%; hazard ratio (HR): 0.74; 95% confidence interval (CI): 0.65-0.84; p < 0.001). In addition, the surface under the cumulative ranking curve (SUCRA) ranking from the network analysis showed that enzalutamide was the most effective in improving the PFS of mCRPC patients (100%), followed by abiraterone (90.1%) and tasquinimod (84.2%). Additionally, targeted agents could clearly prolong OS in mCRPC patients (I2 = 71.6%; HR: 0.91; 95% CI: 0.85-0.97; p < 0.001). Furthermore, based on SUCRA ranking, enzalutamide was the most effective in improving the OS of mCRPC patients (97.2%), followed by abiraterone (91.1%) and zibotentan (65.8%). Intetumumab was associated with the lowest incidence of severe AEs (94.9%), followed by atrasentan (85.1%) and placebo (79.3%). CONCLUSION: In patients with mCRPC, enzalutamide, abiraterone and tasquinimod can prolong PFS, and enzalutamide and abiraterone can prolong OS. Additionally, enzalutamide and abiraterone can improve both PFS and OS with a low risk of causing severe AEs. PMID- 29797222 TI - Metabolic reconstruction and experimental verification of glucose utilization in Desulfurococcus amylolyticus DSM 16532. AB - Desulfurococcus amylolyticus DSM 16532 is an anaerobic and hyperthermophilic crenarchaeon known to grow on a variety of different carbon sources, including monosaccharides and polysaccharides. Furthermore, D. amylolyticus is one of the few archaea that are known to be able to grow on cellulose. Here, we present the metabolic reconstruction of D. amylolyticus' central carbon metabolism. Based on the published genome, the metabolic reconstruction was completed by integrating complementary information available from the KEGG, BRENDA, UniProt, NCBI, and PFAM databases, as well as from available literature. The genomic analysis of D. amylolyticus revealed genes for both the classical and the archaeal version of the Embden-Meyerhof pathway. The metabolic reconstruction highlighted gaps in carbon dioxide-fixation pathways. No complete carbon dioxide-fixation pathway such as the reductive citrate cycle or the dicarboxylate-4-hydroxybutyrate cycle could be identified. However, the metabolic reconstruction indicated that D. amylolyticus harbors all genes necessary for glucose metabolization. Closed batch experimental verification of glucose utilization by D. amylolyticus was performed in chemically defined medium. The findings from in silico analyses and from growth experiments are discussed with respect to physiological features of hyperthermophilic organisms. PMID- 29797223 TI - The heterologous expression potential of an acid-tolerant Talaromyces pinophilus beta-glucosidase in Saccharomyces cerevisiae. AB - A filamentous fungus displaying high cellulase activity was isolated from a compost heap with triticale (a wheat-rye hybrid) as the main constituent. It was preliminarily identified as a Talaromyces pinophilus species. A 2577 base pair beta-glucosidase gene was cloned from complementary DNA and heterologously expressed in Saccharomyces cerevisiae. The recombinant beta-glucosidase production profile was assessed and compared to that of the Saccharomycopsis fibuligera beta-glucosidase which served as a benchmark. The enzyme was also characterised in terms of pH and temperature tolerance as well as response to inhibitors. Maximal extracellular beta-glucosidase activity of 0.56 nkat/mg total protein was measured using p-nitrophenyl-beta-D-glucopyranoside as substrate. The recombinant protein displayed a pH optimum of 4.0, and good thermostability as 70% of maximal enzyme activity was retained after 1 h at 60 degrees C. Activity of the recombinant beta-glucosidase was adversely affected by the presence of glucose and ethanol at higher concentrations while xylose had no effect. The expression of the T. pinophilus beta-glucosidase did not reach the same titres as for the benchmark; however, in the context of constructing a yeast strain for bioethanol production in a consolidated bioprocess, the enzyme may still show good potential. PMID- 29797224 TI - Rapid and simultaneous detection of Salmonella spp., Escherichia coli O157, and Listeria monocytogenes by magnetic capture hybridization and multiplex real-time PCR. AB - The application of rapid, specific, and sensitive methods for pathogen detection and quantification is very advantageous in diagnosis of human pathogens in several applications, including food analysis. The aim of this study was the evaluation of a method for the multiplexed detection and quantification of three significant foodborne pathogenic species (Escherichia coli O157, Salmonella spp., and Listeria monocytogenes). The assay combines specific DNA extraction by multiplex magnetic capture hybridization (mMCH) with multiplex real-time PCR. The amplification assay showed linearity in the range 106-10 genomic units (GU)/PCR for each co-amplified species. The sensitivity corresponded to 1 GU/PCR for E. coli O157 and L. monocytogenes, and 10 GU/PCR for Salmonella spp. The immobilization process and the hybrid capture of the MCH showed good efficiency and reproducibility for all targets, allowing the combination in equal amounts of the different nanoparticle types in mMCH. MCH and mMCH efficiencies were similar. The detection limit of the method was 10 CFU in samples with individual pathogens and 102 CFU in samples with combination of the three pathogens in unequal amounts (amount's differences of 2 or 3 log). In conclusion, this multiplex molecular platform can be applied to determine the presence of target species in food samples after culture enrichment. In this way, this method could be a time-saving and sensitive tool to be used in routine diagnosis. PMID- 29797225 TI - Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) Virus from an Adult Case in Fujian Province, China. PMID- 29797228 TI - Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT R). AB - BACKGROUND: Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. AIMS: To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. METHODS: Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores <= 4 of a maximum score of 8. RESULTS: Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. CONCLUSION: Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline. PMID- 29797226 TI - Short-Term Effects of Cerebellar tDCS on Standing Balance Performance in Patients with Chronic Stroke and Healthy Age-Matched Elderly. AB - Transcranial direct current stimulation (tDCS) may serve as an adjunct approach in stroke rehabilitation. The cerebellum could be a target during standing balance training due to its role in motor adaptation. We tested whether cerebellar tDCS can lead to short-term effects on standing balance performance in patients with chronic stroke. Fifteen patients with a chronic stroke were stimulated with anodal stimulation on the contra-lesional cerebellar hemisphere, ipsi-lesional cerebellar hemisphere, or sham stimulation, for 20 min with 1.5 mA in three sessions in randomized order. Ten healthy controls participated in two sessions with cerebellar stimulation ipsi-lateral to their dominant leg or sham stimulation. During stimulation, subjects performed a medio-lateral postural tracking task on a force platform. Standing balance performance was measured directly before and after each training session in several standing positions. Outcomes were center of pressure (CoP) amplitude and its standard deviation, and velocity and its standard deviation and range, subsequently combined into a CoP composite score (comp-score) as a qualitative outcome parameter. In the patient group, a decrease in comp-score in the tandem position was found after contra lesional tDCS: beta = - 0.25, CI = - 0.48 to - 0.03, p = 0.03. No significant differences in demographics and clinical characteristics were found between patients who responded (N = 10) and patients who did not respond (N = 5) to the stimulation. Contra-lesional cerebellar tDCS shows promise for improving standing balance performance. Exploration of optimal timing, dose, and the relation between qualitative parameters and clinical improvements are needed to establish whether tDCS can augment standing balance performance after stroke. PMID- 29797229 TI - Correction to: Editorial: Special Issue on Heart Valve Mechanobiology : New Insights into Mechanical Regulation of Valve Disease and Regeneration. AB - Original article has been updated to include names and affiliations of authors. PMID- 29797227 TI - Physical training improves thermogenesis and insulin pathway, and induces remodeling in white and brown adipose tissues. AB - Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA IR), homeostasis evaluation of the functional capacity of beta-cells (HOMA-beta), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator activated receptor gamma coactivator 1-alpha and beta (PGC-1alpha, PGC-1beta), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells. PMID- 29797231 TI - Psychometric Evaluation of a Revised Scoring Approach for the Children's Saving Inventory in a Canadian Sample of Youth With Obsessive-Compulsive Disorder. AB - The Children's Saving Inventory (CSI) was introduced in 2011 and is the first parent-rated questionnaire specifically designed to measure the severity of hoarding symptoms in youth. To date, however, no replication studies of the CSI have been published. Additionally, the total CSI score includes several items measuring acquisition, a behavioural dimension that has since been excluded from DSM-5's hoarding disorder criteria. Given these limitations, the primary goal of the present study was to test a modified, DSM-5-consistent, total score of the CSI. Because a confirmatory factor analysis did not support the 2011 four-factor model of the CSI, we reviewed the original CSI and excluded all acquisition items. An exploratory factor analysis yielded a strong three-factor solution (difficulty discarding, Clutter, and distress/impairment) with good reliability and validity for a 15-item version of the CSI. Overall, our results support the use of the 15-item CSI in youth with OCD. PMID- 29797230 TI - Geometry of the left ventricular outflow tract assessed by 3D TEE in patients with aortic stenosis: impact of upper septal hypertrophy on measurements of Doppler-derived left ventricular stroke volume. AB - BACKGROUND: It is unclear how upper septal hypertrophy (USH) affects Doppler derived left ventricular stroke volume (SV) in patients with AS. The aims of this study were to: (1) validate the accuracy of 3D transesophageal echocardiography (TEE) measurements of the left ventricular outflow tract (LVOT), (2) evaluate the differences in LVOT geometry between AS patients with and without USH, and (3) assess the impact of USH on measurement of SV. METHODS: In protocol 1, both 3D TEE and multi-detector computed tomography were performed in 20 patients with AS [aortic valve area (AVA) <= 1.5 cm2]. Multiplanar reconstruction was used to measure the LVOT short and long diameters in four parts from the tip of the septum to the annulus. In protocol 2, the same 3D TEE measurements were performed in AS patients (AVA <= 1.5 cm2, n = 129) and controls (n = 30). We also performed 2D and 3D transthoracic echocardiography in all patients. RESULTS: In protocol 1, excellent correlations of LVOT parameters were found between the two modalities. In protocol 2, the USH group had smaller LVOT short and long diameters than the non-USH group. Although no differences in mean pressure gradient, or SV calculated with the 3D method existed between the two groups, the USH group had greater SV calculated with the Doppler method (73 +/- 15 vs. 66 +/- 15 ml) and aortic valve area (0.89 +/- 0.26 vs. 0.73 +/- 0.24 cm2) than the non-USH group. CONCLUSIONS: 3D TEE can provide a precise assessment of the LVOT in AS. USH affects the LVOT geometry in patients with AS, which might lead to inaccurate assessments of disease severity. PMID- 29797233 TI - Functional heterogeneity of circulating T regulatory cell subsets in breast cancer patients. AB - BACKGROUND: Regulatory T cells (Tregs) play a major role in tumor escape from immunosurveillance by suppressing effector cells. The number of Tregs is increased in tumor sites and peripheral blood of breast cancer patients. However, the data regarding phenotypic and functional heterogeneity of Treg subpopulations in breast cancer are limited. The present study aimed to investigate the number and suppressive potential of Tregs that possess natural naive-(N nTregs), effector/memory-like (EM nTregs), and Tr1-like phenotypes in breast cancer patients and healthy women. METHODS: The study included 10 HW and 17 primary breast cancer patients. Numbers of CD4+CD25+FoxP3+CD45RA+ N nTregs, CD4+CD25+FoxP3+CD45RA- EM nTregs, and CD4+IL-4-IL-10+ Tr1 subsets and the expression of CTLA-4, CD39, GITR, LAP, and IL-35 by these Treg subsets were measured in freshly obtained peripheral blood by flow cytometry. RESULTS: Herein, we demonstrate that the percentages of N nTregs, EM nTregs, CD25+ and FoxP3+ Tr1 cells are elevated in the peripheral blood of breast cancer patients, but do not correlate with cancer stages. Nevertheless, the frequency of CD25+ Tr1 cells was associated with nodal involvement, while the number of EM nTregs correlated with clinical outcome. The expression of CTLA-4 and IL-35 by all assessed Treg subsets was increased throughout all tumor stages (I-III). CONCLUSIONS: Collectively, the current study shows phenotypic alterations in suppressive receptors of Treg subsets, suggesting that breast cancer patients have increased activity of N nTregs, EM nTregs and Tr1 cells; and EM nTregs and CD25+ Tr1 cells represent prospective markers for assessing disease prognosis. PMID- 29797234 TI - Artesunate promotes G2/M cell cycle arrest in MCF7 breast cancer cells through ATM activation. AB - BACKGROUND: Recent studies have revealed that artesunate (ART) has clear anti tumor activity, suggesting that it could be a good candidate chemotherapeutic agent. In this study, we researched the inhibitory effect of ART on MCF7 cells and explored the possible mechanisms. METHODS: MTT assay was used to detect the effect of ART on the proliferation of MCF7 cells. Crystal violet staining was used to observe morphological and quantitative changes. Flow cytometry was used to detect the cell cycle of the drug-acting MCF7 cells. In addition, western blotting was used to detect the drug influence on expression of the ATM, phospho ATM(S1981), H2AX, gammaH2AX(S139), CHK2 and phospho-CHK2(T68), cdc25C, and phospho-cdc25C(S216). RESULTS: In the experimental groups, the proliferation of MCF7 cells was inhibited in a dose-dependent manner and the original cell morphology was lost. The number of G2/M phase cells in the experimental groups increased significantly, and the expression of DNA damage response-associated proteins was significantly increased, such as phospho-ATM(S1981), gammaH2AX(S139), phospho-CHK2(T68), and phospho-cdc25C(S216). CONCLUSIONS: ART can inhibit cell proliferation and promote G2/M arrest in MCF7 cells through ATM activation and the ensuing "ATM-Chk2-Cdc25C" pathway, thus implicating ART as a novel candidate for breast cancer chemotherapy. PMID- 29797232 TI - Current Modalities and Mechanisms Underlying Cardioprotection by Ischemic Conditioning. AB - Ischemic preconditioning is a process which serves to mitigate reperfusion injury. Preconditioning of the heart can be achieved through natural, pharmacological, and mechanical means. Mechanical preconditioning appears to have the greatest chance of good outcomes while methods employing pharmacologic preconditioning have been largely unsuccessful. Remote ischemic preconditioning achieves a cardioprotective effect by applying cycles of ischemia and reperfusion in a distal limb, stimulating the release of a neurohumoral cardioprotective factor incited by stimulation of afferent neurons. The cardioprotective factor stimulates the reperfusion injury salvage kinase (RISK) and survivor activator factor enhancement (SAFE) signaling cascades in cardiomyocytes which promote cell survival by the expression of anti-apoptotic genes and inhibition of the opening of mitochondrial permeability transition pores. Clinical application of ischemic preconditioning involving targets in the RISK and SAFE signaling appears promising in the treatment of acute myocardial infarction; however, clinical trials have yet to demonstrate additional benefit to current therapy. PMID- 29797235 TI - Pharmacokinetic and Pharmacodynamic Modelling to Characterize the Tolerability of Alternative Up-Titration Regimens of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: In the OPTIMIZE study, 4 weeks of roflumilast 250 ug once daily before escalation to the approved 500 ug once daily maintenance dose reduced treatment discontinuations and improved tolerability to roflumilast among patients with chronic obstructive pulmonary disease (COPD). In this study, we present the pharmacokinetic (PK) results and PK/pharmacodynamic (PD) modelling data from OPTIMIZE. METHODS: OPTIMIZE was a multicentre, double-blind, phase III study in which patients with severe COPD were randomized 1:1:1 to receive oral roflumilast 250 MUg once daily, 500 MUg every other day, or 500 MUg once daily for 4 weeks, followed by 500 MUg once daily for 8 weeks. A population PK (popPK) model characterized roflumilast exposure levels (total phosphodiesterase-4 inhibition [tPDE4i]). Furthermore, models characterized the percentage of patients with adverse events (AEs) of interest (PK/AE model), and time to discontinuation due to such AEs (PK/time-to-event model). RESULTS: The popPK model adequately described average plasma concentrations and variability from 1238 patients. The percentage of patients with AEs of interest increased with predicted tPDE4i exposure (logit scale slope 0.484; confidence interval 0.262 0.706; p = 2 * 10-5). PK/time-to-event model analysis predicted that patients receiving the 250 MUg up-titration regimen had significantly lower discontinuation rates and longer time to discontinuation compared with roflumilast 500 MUg every other day or 500 MUg once daily (p = 0.0014). CONCLUSIONS: In this PK/PD model, a 4-week up-titration regimen with roflumilast 250 ug once daily was found to reduce discontinuations and improve tolerability, confirming the main clinical findings of the OPTIMIZE study. However, use of this lower dose as long-term maintenance therapy may not induce sufficient phosphodiesterase-4 inhibition to exert clinical efficacy, supporting the approval of 500 ug as maintenance dose. TRIAL REGISTRATION: OPTIMIZE: NCT02165826; REACT: NCT01329029. PMID- 29797236 TI - Anticoagulation and antiplatelet therapy in acute coronary syndromes: choosing between the Scylla of bleeding and the Charybdis of ischaemic events. PMID- 29797237 TI - Effects of 10 weeks of regular running exercise with and without parallel PDTC treatment on expression of genes encoding sarcomere-associated proteins in murine skeletal muscle. AB - Physical exercise can induce various adaptation reactions in skeletal muscle tissue, such as sarcomere remodeling. The latter involves degradation of damaged sarcomere components, as well as de novo protein synthesis and sarcomere assembly. These processes are controlled by specific protease systems in parallel with molecular chaperones that assist in folding of newly synthesized polypeptide chains and their incorporation into sarcomeres. Since acute exercise induces oxidative stress and inflammation, leading to activation of the transcription factor NFkappaB (nuclear factor kappa B), we speculated that this transcription factor might also play a role in the regulation of long-term adaptation to regular exercise. Thus, we studied skeletal muscle adaptation to running exercise in a murine model system, with and without parallel treatment with the NFkappaB inhibitory, anti-oxidant and anti-inflammatory drug pyrrolidine dithiocarbamate (PDTC). In control mice, 10 weeks of uphill (15 degrees incline) treadmill running for 60 min thrice a week at a final speed of 14 m/min had differential, but only minor effects on many genes encoding molecular chaperones for sarcomere proteins, and/or factors involved in the degradation of the latter. Furthermore, there were marked differences between individual muscles. PDTC treatment modulated gene expression patterns as well, both in sedentary and exercising mice; however, most of these effects were also modest and there was little effect of PDTC treatment on exercise-induced changes in gene expression. Taken together, our data suggest that moderate-intensity treadmill running, with or without parallel PDTC treatment, had little effect on the expression of genes encoding sarcomere components and sarcomere-associated factors in murine skeletal muscle tissue. PMID- 29797238 TI - Brain herniation into the transverse sinuses' arachnoid granulations in the pediatric population investigated with 3 T MRI. AB - We aimed to evaluate the frequency, radiological-clinical findings of brain herniation into arachnoid granulation (BHAG) in pediatric age group using 3 T magnetic resonance imaging. Patients were under 18 years of age and underwent brain MRI examination which consists of 3D T1, 3D T2 FLAIR and 3D T2 sequences. A total of 2320 patients were enrolled in the study. All cases of AG into transverse sinus were included. The location of the AG, the deep, transverse, vertical and neck diameters and volume of AG were recorded. Clinical findings and imaging findings of patients were also recorded. The patients were categorized as BHAG and AG without brain herniation (AGWBH). The mean diameters (deep, transverse, vertical and neck) of AG, volume of AG, age, sex, clinical findings and imaging findings were evaluated and compared in each group. 135 patients (71 female, 64 male) had AG in a total of 2320 patients (prevalence 5.81%). Fifteen patients (10.7% of all patients, 11 female, 4 male) had BHAG. The mean diameters (deep, transverse, vertical and neck) and volume of AGWBH were 5.23 +/- 1.91, 4.07 +/- 1.58, 4.99 +/- 1.68, 3.64 +/- 1.84 mm and 85.05 +/- 89.10 mm3, respectively. The mean diameters (deep, transverse, vertical and neck) and volume of BHAG were 7.46 +/- 2.6, 6.85 +/- 2.34, 8.32 +/- 2.35, 5.41 +/- 1.79 mm and 331 +/- 361.26 mm3, respectively. The mean diameters and volume of BHAG were significantly larger than AGWBH (p < 0.001 for all parameters). There was no significant difference related to clinical and imaging findings between groups (p > 0.05). Brain herniation into arachnoid granulation is seen in pediatric age group as frequently as adults. Its frequency is not related to age. It is not significantly associated with neurological symptoms. As the AG size increases, the risk of BHAG increases. PMID- 29797239 TI - Association of Statin Use with Increased Risk of Musculoskeletal Conditions: A Retrospective Cohort Study. AB - INTRODUCTION: Musculoskeletal conditions, including osteoarthritis (OA), result in tremendous disability and cost. Statins are among the most commonly prescribed medications and their use for primary prevention in many otherwise healthy individuals, including those who are physically active, is increasing. There is conflicting evidence regarding the relationship of statin use and musculoskeletal conditions. Given the rising disability associated with musculoskeletal conditions, understanding predisposing factors, including medication-related exposures, deserves further attention. OBJECTIVES: We examined the association between statin use and the risk of being diagnosed with non-traumatic arthropathies, use-related injury, and undergoing rehabilitation in a cohort with longitudinal follow-up. METHODS: Patients enrolled in a regional military healthcare system between 2003 and 2012 were evaluated in this retrospective cohort study. A propensity score was generated to match statin-users and nonusers using 115 baseline characteristics. Outcomes included ICD-9 diagnoses codes for Agency for Healthcare Research and Quality disease categories of: non-traumatic arthropathies, use-related injury and undergoing rehabilitation. Primary analysis examined the outcomes in statin-users and nonusers after propensity score matching using conditional logistic regression analysis. RESULTS: Initially, 60,455 patients were identified. We propensity score-matched 6728 statin users with 6728 nonusers (52 years of age, ~ 47% women). In the propensity score matched cohort, non-traumatic arthropathies occurred in 59.8% of statin users and 56.0% of nonusers [odds ratio (OR) 1.17, 95% confidence interval (95% CI) 1.09 1.25] and use related injury occurred in 31.9% of statin users and 29.8% of nonusers (OR 1.11, 95% CI 1.03-1.19). There was no difference between statin users and nonusers undergoing rehabilitation (22.6% among statin users, 21.9% among nonusers, OR 1.04, 95% CI 0.96-1.13). CONCLUSION: Statin use was associated with a significant increased risk of non-traumatic arthropathies and use-related injury. Our results provide additional data that can inform patient and clinician conversations about the benefits and risks of statin use. PMID- 29797240 TI - Coronary Events After Dispensing of Ibuprofen: A Propensity Score-Matched Cohort Study Versus Paracetamol in the French Nationwide Claims Database Sample. AB - INTRODUCTION: Non-steroidal anti-inflammatory drugs are associated with a dose and duration-dependent coronary risk. There is little information concerning analgesic-dose ibuprofen, among the most widely used drugs worldwide. OBJECTIVE: Our objective was to measure the risks of acute coronary syndrome (ACS) after dispensing of ibuprofen, versus paracetamol. METHODS: Propensity score 1:2 matched cohorts of ibuprofen or paracetamol treatment episodes (TEs) in Echantillon Generaliste de Beneficiaires (EGB), the 1/97 sample of Systeme National des Donnees de Sante (SNDS), the French nationwide claims database, from 2009 to 2014, were compared. Outcomes were hospital admissions for ACS during the 3 months after the dispensing of ibuprofen or paracetamol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated overall and stratified on low dose aspirin dispensing. RESULTS: A total of 315,269 ibuprofen TEs in 168,400 persons were matched to 630,457 paracetamol TEs in 395,952 patients. Event rates were 50-100 times higher in low-dose aspirin users (27 vs 0.28 per 1000 patient years). Overall there was no difference in risk of ACS at 3 months (HR 0.94, 95% CI 0.74-1.20) despite a transient increase in the first 2 weeks in ibuprofen users (HR 1.70, 95% CI 1.11-2.59). In the stratified analysis, this short-term risk was only found in aspirin users (5% of population, HR 1.84, 95% CI 1.24 3.24), but not in non-aspirin users (HR 1.09, 95% CI 0.40-2.94). CONCLUSIONS: There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol. PMID- 29797243 TI - The Impact of Recruitment on the Dynamics of an Immune-Suppressed Within-Human Host Model of the Plasmodium falciparum Parasite. AB - A model is developed and used to study within-human malaria parasite dynamics. The model integrates actors involved in the development-progression of parasitemia, gametocytogenesis and mechanisms for immune response activation. Model analyses under immune suppression reveal different dynamical behaviours for different healthy red blood cell (HRBC) generation functions. Existence of a threshold parameter determines conditions for HRBCs depletion. Oscillatory dynamics reminiscent of malaria parasitemia are obtained. A dependence exists on the type of recruitment function used to generate HRBCs, with complexities observed for a more nonlinear function. An upper bound that delimits the size of feasible parasitized steady-state solution exists for a logistic function but not a constant function. The upper bound is completely characterized and is affected by parameters associated with HRBCs recruitment, parasitized red blood cells generation and the release and time-to-release of free merozoites. A stable density size for mature gametocytes, the bridge to invertebrate hosts, is derived. PMID- 29797242 TI - Estrogenic effects of phytoestrogens derived from Flemingia strobilifera in MCF-7 cells and immature rats. AB - Phytoestrogen (PE) has received considerable attention due to the physiological significance of its estrogenicity. Flemingia strobilifera (FS) has been used as a folk medicine in Asia for the treatment of inflammation, cancer, and infection; however, the estrogenic effects and chemical components of FS have not yet been reported. We aimed to uncover the estrogenic properties and PEs derived from FS using phytochemical and pharmacological evaluation. PEs from FS extract (FSE) were analyzed by NMR, HPLC, and MS. To evaluate estrogenic activity, FSE and its compounds were evaluated by in vitro and in vivo assays, including human estrogen receptor alpha (hERalpha) binding, estrogen response element (ERE)-luciferase reporter assays, and uterotrophic assays. FSE and its compounds 1-5 showed binding affinities for hERalpha and activated ERE transcription in MCF-7 cells. Additionally, FSE and compounds 1-5 induced MCF-7 cell proliferation and trefoil factor 1 (pS2) expression. In immature female rats, significant increases in uterine weight and pS2 gene were observed in FSE-treated groups. We identified estrogenic activities of FSE and its bioactive compounds, suggesting their possible roles as PEs via ERs. PEs derived from FSE are promising candidates for ER-targeted therapy for post-menopausal symptoms. PMID- 29797241 TI - Role of PKM2 in directing the metabolic fate of glucose in cancer: a potential therapeutic target. AB - BACKGROUND: Many of the hallmarks of cancer are not inherently unique to cancer, but rather represent a re-enactment of normal host responses and activities. A vivid example is aerobic glycolysis ('Warburg effect'), which is used not only by cancer cells but also by normal cells that undergo rapid proliferation. A common feature of this metabolic adaptation is a shift in the expression of pyruvate kinase (PK) isoform M1 to isoform M2. Here, we highlight the key role of PKM2 in shifting cancer metabolism between ATP production and biosynthetic processes. Since anabolic processes are highly energy dependent, the fate of glucose in energy production versus the contribution of carbon in biosynthetic processes needs to be finely synchronised. PKM2 acts to integrate cellular signalling and allosteric regulation of metabolites in order to align metabolic activities with the changing needs of the cell. CONCLUSIONS: The central role of PKM2 in directing the flow of carbon between catabolic (ATP-producing) and anabolic processes provides unique opportunities for extending the therapeutic window of currently available and/or novel anti-neoplastic agents. PMID- 29797244 TI - The Last Jedi Takes His Own Life: Rational Suicide and Homicide-Suicide in Star Wars. PMID- 29797245 TI - Colonic conduit prolapse after transanal total mesorectal excision (taTME). PMID- 29797246 TI - Embolization of superior rectal arteries for transfusion dependent haemorrhoidal bleeding in severely cardiopathic patients: a new field of application of the "emborrhoid" technique. PMID- 29797248 TI - ELDA qASO-PCR for High Sensitivity Detection of Tumor Cells in Bone Marrow and Peripheral Blood. AB - A quantitative allele-specific polymerase chain reaction in combination with an extreme limiting dilution approach (ELDA qASO-PCR) enables the detection of tumor cells in patients with multiple myeloma (MM) in bone marrow (BM) samples and in peripheral blood (PB) with a sensitivity of <10-6. The two-step procedure of patient-specific tumor cell identification via the immunoglobulin heavy chain (IgH) and kappa/lambda light chain (k/lambda LC) locus, followed by tumor cells quantification by ELDA qASO-PCR allows for the application of this method to the majority of MM patients, including those with Bence Jones proteinuria. PMID- 29797249 TI - EuroFlow-Based Next-Generation Flow Cytometry for Detection of Circulating Tumor Cells and Minimal Residual Disease in Multiple Myeloma. AB - Here, we describe the detailed protocol for minimal residual disease (MRD) assessment as well as circulating tumor cell (CTC) detection in patients with plasma cell disorders using the next-generation flow (NGF) method developed by EuroFlow. This includes the previous setup of flow cytometers, preparation and staining of samples, cell acquisition, quality control of instruments, methods and samples, as well as data interpretation to monitor MRD and CTCs with great sensitivity. It should be noted that the NGF method fully described below can be equally applied to monitor MRD in patients with systemic light-chain amyloidosis and to detect occult bone marrow involvement in patients with solitary plasmocytoma. PMID- 29797250 TI - Cytoplasmic Immunoglobulin Vs. DNA Analysis by Flow Cytometry. AB - Cytoplasmic immunoglobulin (CIg) vs DNA by flow cytometric (FCM) method allows us to detect DNA content of the neoplastic plasma cells with monotypic cytoplasmic immunoglobulin and also provide us with clear distinction from normal polytypic plasma cells. Abnormalities in cellular DNA content (DNA aneuploidy) and cell cycle determination (proliferative activity) can be measured rapidly by flow cytometry. FCM can measure gross differences in DNA content and distinguish a cell population with normal DNA content, or diploid from a cell population with an abnormal or aneuploid DNA content. With the dual parameter procedure a monoclonal plasma cell population can be identified down to less than 0.1-0.05% of all cells. PMID- 29797251 TI - Deep Profiling of the Immune System of Multiple Myeloma Patients Using Cytometry by Time-of-Flight (CyTOF). AB - Mass cytometry has emerged as a new state-of-the-art technology that enables in depth characterization of cellular populations and functions at a single cell resolution. We describe the application of this technology to deeply phenotype the blood and bone marrow components of multiple myeloma patients in a clinical setting. This technology allows for simultaneous quantification of more than 40 markers, overcoming the challenges of traditional fluorescence-based flow cytometry. PMID- 29797252 TI - Fluorescence In Situ Hybridization (FISH) in Multiple Myeloma. AB - The application of fluorescence in situ hybridization (FISH) technology in diagnosis and molecular classification of cancer-risk has become an essential tool in the proceeding of personalized therapy. In multiple myeloma, the precise FISH detection of numerical and structural genetic aberrations can be carried out on metaphase chromosome spreads, interphase nuclei, and formalin fixed paraffin embedded (FFPE) tissues. To dissect highly complex cancer genomes, a broad variety of novel DNA probes, which outpace supplies from commercial resources on the market, are also crucial to the advanced translational researches. Here, we provide the protocols for the creation of custom-made DNA probes and for conducting hybridizations on various targeting cells and tissues. PMID- 29797253 TI - Whole Exome Sequencing in Multiple Myeloma to Identify Somatic Single Nucleotide Variants and Key Translocations Involving Immunoglobulin Loci and MYC. AB - Multiple myeloma is a malignancy of terminally differentiated plasma cells in the bone marrow. These plasma cells produce high levels of immunoglobulin which cause end-organ damage. Rearrangements within the immunoglobulin loci are a physiological part of B cell development, but these DNA level double-strand breaks may result in interchromosomal translocations. There are five main translocations involving the Ig loci: t(4;14) 12%, t(6;14) 1%, t(11;14) 15%, t(14;16) 3%, and t(14;20) 2%. These are primary events, found in all cells within the tumor clone and are associated with different prognosis. The t(4;14), t(14;16), and t(14;20) are associated with a poor prognosis, whereas the others are associated with a more favorable prognosis. Rearrangements at the MYC locus are also associated with a poor prognosis and increased expression of MYC. MYC rearrangements are frequent (25%) and involve interchromosomal translocations involving Ig loci or other partners, but also include intrachromosomal inversions, duplications and deletions. As such, the Ig and MYC loci are key players in the myeloma genome and including these in any genomic studies is key to understanding the relationship with other abnormalities. We have designed a custom capture of the Ig and MYC loci which can be added to exome or targeted captures to inform on these key events. This saves on performing additional tests to determine these events, which are generally mandatory for any genetic investigations in myeloma. This custom capture is also relevant to other B cell malignancies where MYC and Ig translocations occur. PMID- 29797247 TI - Nutritional treatment of advanced CKD: twenty consensus statements. AB - The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and/or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED). PMID- 29797254 TI - RNA-Sequencing from Low-Input Material in Multiple Myeloma for Application in Clinical Routine. AB - RNA sequencing is a recently developed approach for transcriptome profiling with several advantages over gene expression profiling using DNA microarrays. Here we describe a RNA-sequencing protocol optimized for low-input analysis of total RNA from CD138+ purified plasma cells from myeloma patients which is applicable in clinical routine. PMID- 29797255 TI - Protocol for M3P: A Comprehensive and Clinical Oriented Targeted Sequencing Panel for Routine Molecular Analysis in Multiple Myeloma. AB - Over the past 10 years next generation sequencing (NGS) approaches deciphered a large number of genomes from a wide variety of tumor types. However, despite most relevant findings, this technology has not yet been implemented into standard diagnostic workflows. Broad access to NGS technology is still limited, sequencing/analysis times exceed clinically relevant timeframes and despite huge cuts, costs remain significant. We proposed a custom-tailored gene panel, which focuses on a selected number of relevant genes and developed a clinically oriented NGS targeted sequencing approach for the molecular characterization of Multiple Myeloma (MM) tumors, allowing the description of the tumor genetic heterogeneity and its changes under selective pressure of antitumor therapy, in a more cost effective and faster turnaround timeframe. PMID- 29797256 TI - Analysis of Circulating Tumor DNA. AB - Circulating tumor DNA (ctDNA) analysis is currently gaining momentum as an innovative methodology for characterizing the tumor genome and monitoring therapeutic efficacy in the multifocal, genetically and spatially heterogeneous plasma cell malignancy, multiple myeloma (MM). Circulating cell-free DNA (cfDNA), which consists of a combination of DNA derived from both tumor and normal cells, is present in extracellular bodily fluids. The presence of ctDNA within this admixture has been demonstrated recently in MM. In this chapter, we describe the routinely utilized methodology for the extraction and longitudinal analysis of specific mutations present in ctDNA derived from peripheral blood plasma of MM patients. PMID- 29797257 TI - Detection of Cross-Sample Contamination in Multiple Myeloma Samples and Sequencing Data. AB - The increasing applicability and sensitivity of next generation sequencing methods exacerbate one of the main issues in the molecular biology laboratory, namely cross-sample contamination. This type of contamination, which could massively increase the rate of false-positive calls in sequencing experiments, can originate at each step during the processing of multiple myeloma samples, such as CD138-selection of tumor cells, RNA and DNA isolation or the processing of sequencing libraries. Here we describe a Droplet Digital PCR (ddPCR) method and a simple bioinformatic solution for the detection of contamination in patient's samples and derived sequencing data, which are based on the same principle: detection of alternative alleles for single-nucleotide polymorphisms (SNPs) that are homozygous according to the control (germ line) sample. PMID- 29797258 TI - Analysis of Global Gene Expression Profiles. AB - DNA microarrays have considerably helped to improve the understanding of biological processes and diseases including multiple myeloma (MM). GEP analyses have been successful to classify MM, define risk, identify therapeutic targets, predict treatment response, and understand drug resistance.This generated large amounts of publicly available data that could benefit from easy-to-use bioinformatics resources to analyze them. Here we present easy-to-use and open access bioinformatics tools to extract and visualize the most prominent information from GEP data. PMID- 29797259 TI - Genome Wide Mapping of Methylated and Hydroxyl-Methylated Cytosines Using a Modified HpaII Tiny Fragment Enrichment by Ligation Mediated PCR Tagged Sequencing Protocol. AB - Here we describe a method for genome wide investigation of methylation and hydroxymethylation status of cytosines. This protocol is an improvement of the HELP-tagging protocol previously described by Suzuki et al. It involves the glucosylation of 5-hydroxymethylcytosines (5-hmC) with beta-glucosyl transferase (beta-GT), thus rendering them resistant to digestion by MspI. Parallel digestion of beta-GT treated samples with MspI, untreated sample with MspI and another untreated sample with HpaII, followed by adapter ligation, parallel sequencing and bioinformatics processing results in a differential display of MspI digestion sites that allows the determination of the distribution of 5-methylcytosines (5 mC) and 5-hmC at these sites. PMID- 29797260 TI - A Rapid and Robust Protocol for Reduced Representation Bisulfite Sequencing in Multiple Myeloma. AB - Reduced representation bisulfite sequencing (RRBS) is one of the most comprehensive yet economic ways of mapping whole genome DNA-methylation. Here, we have substantially modified the RRBS protocol by combining end-repair and A tailing steps, and by introducing a bead-based method for rapid and easy size selection of the library molecules. The method has been optimized for myeloma clinical samples, where the input DNA concentration can be as low as 100 ng. The method developed can be accomplished in 3 days, including the initial overnight MspI enzyme digestion. Although the protocol has been optimized in myeloma samples, it is broadly applicable to any clinical sample, which is restricted by very low input DNA concentrations. PMID- 29797261 TI - Microfluidic Production and Application of Lipid Nanoparticles for Nucleic Acid Transfection. AB - Lipid nanoparticles (LNPs) are established in the biopharmaceutical industry for efficient encapsulation and cytosolic delivery of nucleic acids for potential therapeutics, with several formulations in clinical trials. The advantages of LNPs can also be applied in basic research and discovery with a microfluidic method of preparation now commercially available that allows preparations to be scaled down to quantities appropriate for cell culture. These preparations conserve expensive nucleic acids while maintaining the particle characteristics that have made LNPs successful in later stages of genetic medicine development. Additionally, this method and the resulting LNPs are seamlessly scalable to quantities appropriate for in vivo models and development of nucleic acid therapeutics.The present work describes the methodology for preparing LNPs loaded with siRNA, mRNA or plasmids using a commercially available microfluidic instrument and an accompanying transfection kit. Guidelines for application to cultured cells in a well-plate format are also provided. PMID- 29797262 TI - Microfluidic Assembly of Liposomes with Tunable Size and Coloading Capabilities. AB - Liposomes used for the delivery of pharmaceuticals have difficulties scaling up and reaching clinical translation as they suffer from batch-to-batch variability. Here, we describe a microfluidic approach for creating reproducible, homogenous nanoparticles with tunable characteristics. These nanoparticles of sizes ranging from 30 to 500 nm are rapidly self-assembled by controlling the flow rates of ethanol and aqueous streams. This method of microfluidic assembly allows for the efficient encapsulation of both hydrophobic and hydrophilic drugs in the lipid bilayer and particle core, respectively, either separately or in combination. PMID- 29797263 TI - Fibre Ultrastructure. AB - Mammalian hair fibres can be structurally divided into three main components: a cuticle, cortex and sometimes a medulla. The cuticle consists of a thin layer of overlapping cells on the surface of the fibre, constituting around 10% of the total fibre weight. The cortex makes up the remaining 86-90% and is made up of axially aligned spindle-shaped cells of which three major types have been recognised in wool: ortho, meso and para. Cortical cells are packed full of macrofibril bundles, which are a composite of aligned intermediate filaments embedded in an amorphous matrix. The spacing and three-dimensional arrangement of the intermediate filaments vary with cell type. The medulla consists of a continuous or discontinuous column of horizontal spaces in the centre of the cortex that becomes more prevalent as the fibre diameter increases. PMID- 29797264 TI - The Follicle Cycle in Brief. AB - This chapter presents a very succinct overview of the cyclic biology of the hair follicle as it transitions from the quiescent telogen stage to the anagen stage in which hairs are actively produced before regressing through the catagen stage to telogen. PMID- 29797265 TI - Diversity of Trichocyte Keratins and Keratin Associated Proteins. AB - Wool and hair fibres are primarily composed of proteins of which the keratins and keratin associated proteins (KAPs) are the major component. Considerable diversity is known to exist within these two groups of proteins. In the case of the keratins two major families are known, of which there are 11 members in the acidic Type I family and 7 members in the neutral-basic Type II family. The KAPs are even more diverse than the keratins, with 35 families being known to exist when the KAPs found in monotremes, marsupials and other mammalian species are taken into consideration. Human hair and wool are known to have 88 and 73 KAPs respectively, though this number rises for wool when polymorphism within KAP families is included. PMID- 29797266 TI - Evolution of Trichocyte Keratins. AB - The evolution of keratins was closely linked to the evolution of epithelia and epithelial appendages such as hair. The characterization of keratins in model species and recent comparative genomics studies have led to a comprehensive scenario for the evolution of keratins including the following key events. The primordial keratin gene originated as a member of the ancient gene family encoding intermediate filament proteins. Gene duplication and changes in the exon intron structure led to the origin of type I and type II keratins which evolved further by nucleotide sequence modifications that affected both the amino acid sequences of the encoded proteins and the gene expression patterns. The diversification of keratins facilitated the emergence of new and epithelium type specific properties of the cytoskeleton. In a common ancestor of reptiles, birds, and mammals, a rise in the number of cysteine residues facilitated extensive disulfide bond-mediated cross-linking of keratins in claws. Subsequently, these cysteine-rich keratins were co-opted for an additional function in epidermal follicular structures that evolved into hair, one of the key events in the evolution of mammals. Further diversification of keratins occurred during the evolution of the complex multi-layered organisation of hair follicles. Thus, together with the evolution of other structural proteins, epithelial patterning mechanisms, and development programmes, the evolution of keratins underlied the evolution of the mammalian integument. PMID- 29797267 TI - Evolution of Trichocyte Keratin Associated Proteins. AB - The major components of hair are keratins and keratin associated proteins (KRTAPs). KRTAPs form the interfilamentous matrix between intermediate filament bundles through extensive disulfide bond cross-linking with the numerous cysteine residues in hair keratins. A variable number of approximately100-180 genes compose the KRTAP gene family in mammals. KRTAP gene family members present a typical pattern of concerted evolution, and its evolutionary features are consistent with the evolution of mammalian hair. KRATP genes might be more important in determining the structure of cashmere fibers in domestic mammals like sheep and goats. KRTAP gene variants thus should provide information for improved wool by sheep and goat breeding. PMID- 29797268 TI - Structural Hierarchy of Trichocyte Keratin Intermediate Filaments. AB - Although trichocyte keratins (hair, wool, quill, claw) have been studied since the 1930s it is only over the last 30 years or so that major advances have been made in our understanding of the complex structural hierarchy of the filamentous component of this important filament-matrix composite. A variety of techniques, including amino acid sequence analysis, computer modelling, X-ray fibre diffraction and protein crystallography, various forms of electron microscopy, and crosslinking methods have now combined to reveal much of the structural detail. The heterodimeric structure of the keratin molecule is clear, as are the highly-specific modes by which these molecules aggregate to form functionally viable IF. The observation that hair keratin can adopt not one but two structurally-distinct conformations, one formed in the living cells at the base of the hair follicle in a reducing environment and the second in the fully differentiated hair in dead cells in an oxidized state, was unexpected but has major implications for the mechanism of hair growth. Insights have also been made into the mechanism of the uppermost level of hair superstructure, relating to the assembly of the IF in the paracortical and orthocortical macrofibrils. PMID- 29797269 TI - Trichocyte Keratin-Associated Proteins (KAPs). AB - The trichocyte (hard alpha-) keratins are epidermal appendages (hair, wool, hoof, horn, claw, baleen and quill) with a classic filament-matrix composite structure. In human hair, for example, keratin intermediate filaments (IF) of diameter 7.5 nm are embedded in a matrix formed from at least 89 different types of keratin associated proteins (KAPs). The latter fall into three families, generally defined in terms of their cysteine residue or glycine plus tyrosine residue content. The KAPs, which infiltrate the space between the IF, are recognized as having especially important roles in the organisation of the IF into macrofibrils, in determining some of the most important physical attributes of the fully-keratinised hair fibre, including its hardness, toughness and pliability, and in linking IF to one another, either directly or indirectly, with a resultant increase in durability and resistance to degradation by microorganisms. Sequence data for many KAPs are now available, and repeating motifs of varying extent have been observed in a number of them. Little, however, is known about their three-dimensional structures, though modelling has indicated that some local structural regularity is likely to exist. Current data suggest that the KAPs in vivo may adopt a variety of energetically-similar conformations stabilized predominantly by intramolecular disulfide bonds. The role of KAPs in hair diseases relates more to modulation in gene expression than to point mutations, in contrast to that observed for the IF proteins. PMID- 29797270 TI - Introduction to Hair Development. AB - The anagen phase of the hair follicle cycle is when the follicle is configured to grow hair. In short hairs (e.g., mouse underhairs and human eye lashes) anagen phase is short, but in the wool of sheep and in human scalp hair anagen is a prolonged state lasting for years. In this chapter we describe the morphological and biological divisions within the anagen follicle. PMID- 29797271 TI - Environment of the Anagen Follicle. AB - Hair follicles are part of the skin. Almost universally, follicles are described as an epithelium-derived tubular down growth into the skin's dermis. Because follicles are complex structures, especially when in anagen phase and configured to actively grow fibres, it is easy to forget that they are part of a crowded environment within the skin. This chapter introduces some of the structures which surround the follicle as well as some of the peripheral parts of the follicle, including follicle groups, and the dermal sheath, vasculature, adipocytes, nerves and the arrector pili muscle. PMID- 29797272 TI - Development of Hair Fibres. AB - The growth of hairs occurs during the anagen phase of the follicle cycle. Hair growth begins with basement membrane-bound stem cells (mother cells) around the dermal papilla neck which continuously bud off daughter cells which further divide as a transient amplifying population. Division ceases as cell line differentiation begins, which entails changes in cell junctions, cell shape and position, and cell-line specific cytoplasmic expression of keratin and trichohyalin. As the differentiating cells migrate up the bulb, nuclear function ceases in cortex, cuticle and inner root sheath (IRS) layers. Past the top of the bulb, cell shape/position changes cease, and there is a period of keratin and keratin-associated protein (KAP) synthesis in fibre cell lines, with increases, in particular of KAP species. A gradual keratinization process begins in the cortex at this point and then non-keratin cell components are increasingly broken down. Terminal cornification, or hardening, is associated with water loss and precipitation of keratin. In the upper follicle, the hair, now in its mature form, detaches from the IRS, which is then extracted of material and becomes fragmented to release the fibre. Finally, the sebaceous and sudoriferous (if present) glands coat the fibre in lipid-rich material and the fibre emerges from the skin. This chapter follows the origin of the hair growth in the lower bulb and traces the development of the various cell lines. PMID- 29797273 TI - Macrofibril Formation. AB - Macrofibrils are the main structural component of the hair cortex, and are a composite material in which trichokeratin intermediate filaments (IFs) are arranged as organised arrays embedded in a matrix composed of keratin-associated proteins (KAPs) and keratin head groups. Various architecture of macrofibrils is possible, with many having a central core around which IFs are helically arranged, an organisation most accurately described as a double-twist arrangement. In this chapter we describe the architecture of macrofibrils and then cover their formation, with most of the material focusing on the theory that the initial stages of macrofibril formation are as liquid crystals. PMID- 29797274 TI - Crosslinking Between Trichocyte Keratins and Keratin Associated Proteins. AB - Trichocyte keratins differ considerably from their epithelial cousins in having a higher number of cysteine residues, of which the greater proportion are located in the head and tail regions of these proteins. Coupled with this is the presence of a large number of keratin associated proteins in these fibres that are high in their cysteine content, the high sulfur proteins and ultra-high sulfur proteins. Thus it is the crosslinking that occurs between the cysteines in the keratins and KAPs that is an important determinant in the functionality of wool and hair fibres. Studies have shown the majority of the cysteine residues are involved in internal crosslinking in the KAPs leaving only a few specific cysteines to interact with the keratins, with most evidence pointing to interactions between these KAP cysteines and the keratin head groups. PMID- 29797275 TI - The Thermodynamics of Trichocyte Keratins. AB - This chapter is an attempt at an excursion into the world of keratins with the help of thermodynamics.After briefly introducing some of the thermodynamic concepts involved in deciphering the behaviour of keratins, we will use them to look into the process of aggregation of keratin molecules into intermediate filaments, and keratin fibres, and then for analysing how keratin materials react to mechanical, thermal and moisture stresses, respectively.In most of the cases entropy appears to be the major driving force of the response occurring in keratins under environmental assault. This fact points to the important role played for keratins by temperature, which, aside from influencing the kinetics of the processes (accelerating or decelerating the rates of the rates), helps increase or decrease the entropic contribution to the Gibbs free energy and, thus, allows thermodynamically the occurrence of the observed behaviour of keratins. PMID- 29797276 TI - Oxidative Modification of Trichocyte Keratins. AB - Oxidation of keratin results in a range of deleterious effects, including discolouration and compromised physical and mechanical properties. Keratin oxidative degradation is driven by molecular-level events, with accumulation of modifications at the protein primary level resulting directly in changes to secondary, tertiary and quaternary structure, as well as eventually changes in the observable physical and chemical properties. Advances in proteomic analysis techniques provide an increasingly clearer insight into the cascade of molecular modification underpinning keratin oxidation and how this translates through to higher order changes in properties. This chapter summarises the effects of oxidation on keratin-based materials, the types of molecular modification associated with this, and advances in techniques and approaches for characterising this modification. PMID- 29797277 TI - Mapping the social impacts of small dams: The case of Thailand's Ing River basin. AB - The social impacts of large dams have been studied extensively. However, small dams' social impacts have been largely neglected by the academic community. Our paper addresses this gap. We examine the social impacts of multiple small dams in one upstream and one downstream village in Thailand's Ing River basin. Our research is based on semi-structured interviews with beneficiaries, government and NGOs. We argue that small dams' social impacts are multi-faceted and unequal. The dams were perceived to reduce fish abundance and provide flood mitigation benefits. Furthermore, the dams enabled increased access to irrigation water for upstream farmers, who re-appropriated water via the dams at the expense of those downstream. The small dams thus engendered water allocation conflicts. Many scholars, practitioners and environmentalists argue that small dams are a benign alternative to large dams. However, the results of our research mandate caution regarding this claim. PMID- 29797278 TI - Illness as the saturated phenomenon: the contribution of Jean-Luc Marion. AB - During the last few decades, many thinkers have advocated for the importance of the phenomenological approach in developing the understanding of the lived experience of illness. In their attempts, they have referred to ideas found in the history of phenomenology, most notably, in the works of Edmund Husserl, Martin Heidegger, Maurice Merleau-Ponty and Jean-Paul Sartre. The aim of this paper is to sketch out an interpretation of illness based on a yet unexplored conceptual framework of the phenomenology of French thinker Jean-Luc Marion. Focusing on concepts of the saturated phenomenon and flesh, the paper develops an interpretation of illness as the saturated phenomenon, which highlights a variety of dimensions of illness already elaborated within the phenomenology of medicine, such as the affective dimension of illness, the disruptive dimension of illness, the transformed perception of the self in illness, mineness of flesh in illness and the inexpressible and hermeneutical dimension of illness. In addition to that, the paper explores some of the consequences the proposed interpretation of illness offers regarding the nature of illness and health. It is argued that illness in its essence is very similar to the experience of other saturated phenomena, suggesting that the difference between them does not lie within the character of the affective givenness, but rather within the dynamic relationship between the affective givenness and its conceptualization. It is also shown that the experience of health is compatible with the experience of saturation and thus is not limited to the tacit and harmonious background state. PMID- 29797279 TI - Correction to: Vitamin D Supplementation in Childhood - A Review of Guidelines. AB - There was mistake on the published online version. A reader has brought to our notice a typographical error in an article entitled "Vitamin D Supplementation in Childhood - A Review of Guidelines" published in Indian J Pediatr. March 2018;85(3):194-201. PMID- 29797281 TI - Postcraniometric sex and ancestry estimation in South Africa: a validation study. AB - With the acceptance of the Daubert criteria as the standards for best practice in forensic anthropological research, more emphasis is being placed on the validation of published methods. Methods, both traditional and novel, need to be validated, adjusted, and refined for optimal performance within forensic anthropological analyses. Recently, a custom postcranial database of modern South Africans was created for use in Fordisc 3.1. Classification accuracies of up to 85% for ancestry estimation and 98% for sex estimation were achieved using a multivariate approach. To measure the external validity and report more realistic performance statistics, an independent sample was tested. The postcrania from 180 black, white, and colored South Africans were measured and classified using the custom postcranial database. A decrease in accuracy was observed for both ancestry estimation (79%) and sex estimation (95%) of the validation sample. When incorporating both sex and ancestry simultaneously, the method achieved 70% accuracy, and 79% accuracy when sex-specific ancestry analyses were run. Classification matrices revealed that postcrania were more likely to misclassify as a result of ancestry rather than sex. While both sex and ancestry influence the size of an individual, sex differences are more marked in the postcranial skeleton and are therefore easier to identify. The external validity of the postcranial database was verified and therefore shown to be a useful tool for forensic casework in South Africa. While the classification rates were slightly lower than the original method, this is expected when a method is generalized. PMID- 29797280 TI - Touch the table before the target: contact with an underlying surface may assist the development of precise visually controlled reach and grasp movements in human infants. AB - Multiple motor channel theory posits that skilled hand movements arise from the coordinated activation of separable neural circuits in parietofrontal cortex, each of which produces a distinct movement and responds to different sensory inputs. Prehension, the act of reaching to grasp an object, consists of at least two movements: a reach movement that transports the hand to a target location and a grasp movement that shapes and closes the hand for target acquisition. During early development, discrete pre-reach and pre-grasp movements are refined based on proprioceptive and tactile feedback, but are gradually coordinated together into a singular hand preshaping movement under feedforward visual control. The neural and behavioural factors that enable this transition are currently unknown. In an attempt to identify such factors, the present descriptive study used frame by-frame video analysis to examine 9-, 12-, and 15-month-old infants, along with sighted and unsighted adults, as they reached to grasp small ring-shaped pieces of cereal (Cheerios) resting on a table. Compared to sighted adults, infants and unsighted adults were more likely to make initial contact with the underlying table before they contacted the target. The way in which they did so was also similar in that they generally contacted the table with the tip of the thumb and/or pinky finger, a relatively open hand, and poor reach accuracy. Despite this, infants were similar to sighted adults in that they tended to use a pincer digit, defined as the tip of the thumb or index finger, to subsequently contact the target. Only in infants was this ability related to their having made prior contact with the underlying table. The results are discussed in relation to the idea that initial contact with an underlying table or surface may assist infants in learning to use feedforward visual control to direct their digits towards a precise visual target. PMID- 29797283 TI - The Danish STR sequence database: duplicate typing of 363 Danes with the ForenSeqTM DNA Signature Prep Kit. AB - Some STR loci have internal sequence variations, which are not revealed by the standard STR typing methods used in forensic genetics (PCR and fragment length analysis by capillary electrophoresis (CE)). Typing of STRs with next-generation sequencing (NGS) uncovers the sequence variation in the repeat region and in the flanking regions. In this study, 363 Danish individuals were typed for 56 STRs (26 autosomal STRs, 24 Y-STRs, and 6 X-STRs) using the ForenSeqTM DNA Signature Prep Kit to establish a Danish STR sequence database. Increased allelic diversity was observed in 34 STRs by the PCR-NGS assay. The largest increases were found in DYS389II and D12S391, where the numbers of sequenced alleles were around four times larger than the numbers of alleles determined by repeat length alone. Thirteen SNPs and one InDel were identified in the flanking regions of 12 STRs. Furthermore, 36 single positions and five longer stretches in the STR flanking regions were found to have dubious genotyping quality. The combined match probability of the 26 autosomal STRs was 10,000 times larger using the PCR-NGS assay than by using PCR-CE. The typical paternity indices for trios and duos were 500 and 100 times larger, respectively, than those obtained with PCR-CE. The assay also amplified 94 SNPs selected for human identification. Eleven of these loci were not in Hardy-Weinberg equilibrium in the Danish population, most likely because the minimum threshold for allele calling (30 reads) in the ForenSeqTM Universal Analysis Software was too low and frequent allele dropouts were not detected. PMID- 29797282 TI - Male individualization using 12 rapidly mutating Y-STRs in Araein ethnic group and shared paternal lineage of Pakistani population. AB - A multiplex assay has been developed with newly designed primer sets comprising high mutation rate 12 RM Y-STR markers (DYS570, DYF399S1, DYS547, DYS612, DYF387S1, DYS449, DYS576, DYS5626, DYF403S1 (a + b), DYS627, DYS526, and DYF404S1). Rapidly mutating Y-STRs were evaluated in 167 male individuals among 97 were unrelated from Araein ethnic group and 70 belonged to shared paternal lineage including 20 pairs of father-son and 15 pairs of brother-brother relationship collected from Punjabi population of Pakistan. Forensic competency parameters were implemented for each marker and exceptionally significant results found wherein polymorphism information content (PIC) was in range of 0.7494 (DYS576) to 0.8994 (DYS627). Samples were also analyzed with Y-filer kit for comparison and marked differentiations observed. Haplotype discrimination capacity was 100% as no haplotype shared among all the unrelated individuals of same ethnic group as compared to 17 Y-filer loci (78%). While in closely related males, discrimination capacity was 96.4% with haplotype diversity value of 0.98. Resulted high mutation rate 1 * 10-2 to 7.14 * 10-2 as compared to Y-filer (1 * 10-4 to 1 * 10-3) manifested the power of RM Y-STRs for considering absolute individualization of interrelated and unrelated male individuals. However, multiplex assay would be useful for male discrimination in mixed DNA specimen, azoospermic males, and multiple male DNA contributors in sexual assault cases and mass disasters victim's identification as well as anthropological studies. PMID- 29797284 TI - Quality Assurance and Improvement in Head and Neck Cancer Surgery: From Clinical Trials to National Healthcare Initiatives. AB - OPINION STATEMENT: It is without question in the best interest of our patients, if we can identify ways to improve the quality of care we deliver to them. Great progress has been made within the last 25 years in terms of development and implementation of quality-assurance (QA) platforms and quality improvement programs for surgery in general, and within this context for head and neck surgery. As of now, we have successfully identified process indicators that impact outcome of our patients and the quality of care we deliver as surgeons. We have developed risk calculators to determine the risk for complications of individual surgical patients. We have created perioperative guidelines for complex head and neck procedures. We have in Europe and North America created audit registries that can gather and analyze data from institutions across the world to better understand which processes need change to obtain good outcomes and improve quality of care. QA platforms can be tested within the clearly defined environment of prospective clinical trials. If positive, such programs could be rolled out within national healthcare systems, if feasible. Testing quality programs in clinical trials could be a versatile tool to help head neck cancer patients benefit directly from such initiatives on a global level. PMID- 29797285 TI - Parkour as a Donor Sport for Athletic Development in Youth Team Sports: Insights Through an Ecological Dynamics Lens. AB - Analyses of talent development in sport have identified that skill can be enhanced through early and continued involvement in donor sports which share affordances (opportunities for action) with a performer's main target sport. Aligning key ideas of the Athletic Skills Model and ecological dynamics theory, we propose how the sport of parkour could provide a representative and adaptive platform for developing athletic skill (e.g. coordination, timing, balance, agility, spatial awareness and muscular strength). We discuss how youth sport development programmes could be (re) designed to include parkour-style activities, in order to develop general athletic skills in affordance-rich environments. It is proposed that team sports development programmes could particularly benefit from parkour-style training since it is exploratory and adaptive nature shapes utilisation of affordances for innovative and autonomous performance by athletes. Early introduction to varied, relevant activities for development of athleticism and skill, in a diversified training programme, would provide impetus for a fundamental shift away from the early specialisation approach favoured by traditional theories of skill acquisition and expertise in sport. PMID- 29797287 TI - Estimating renal function in patients with atrial fibrillation: which dose of direct oral anticoagulants? PMID- 29797286 TI - Effects of vitrification on the viability of alginate encapsulated isolated bovine pre-antral follicles. AB - PURPOSE: Individual follicle cryopreservation techniques, without hydrogel support, are labor-intensive and a substantial proportion of isolated follicles are lost during handling and after warming. Therefore, the viability and morphology of isolated bovine (as a model for human) pre-antral follicles after vitrification and warming, when encapsulated in alginate beads, were investigated. METHODS: Bovine pre-antral follicles were mechanically isolated and divided into four different groups: (1) culture in 2% alginate beads (3D system) and vitrification in beads using mesh cups (3DVIT), (2) culture in 2% alginate beads (3DCUL), (3) culture in 96-well plates (2D system) and vitrification using High Security Vitrification straws(r) (2DVIT), (4) culture in a 2D system (2DCUL). The same vitrification and warming protocols were used for embedded (3DVIT) and non-embedded follicles (2DVIT). RESULTS: No differences were observed in follicle viability between group 2DCUL and 3DCUL. Group 3DVIT showed the lowest viability (45.9%) according to calcein and neutral red staining among all groups. Group 2DVIT displayed the highest viability (87.5%) and largest percentage of follicles with a well-preserved morphology. CONCLUSIONS: Our results show that, using a vitification protocol optimized for non-embedded follicles, 2D culture is more effective in vitrifying isolated follicles. However, embedding in alginate allow to handle follicles more efficiently, i.e., without excessive manipulation and thus less labor-intensive in combination with a reduced loss of follicles during the procedure. Based on the increased work efficiency, but lower viability and higher proportion of follicles showing impaired morphology, we consider it advantageous to optimize the protocol for the vitrification of embedded follicles to increase survival and maintain morphology after vitrification. PMID- 29797289 TI - Getting with the times: a narrative review of the literature on group decision making in virtual environments and implications for promotions committees. AB - INTRODUCTION: Concerns around the time and administrative burden of trainee promotion processes have been reported, making virtual meetings an attractive option for promotions committees in undergraduate and postgraduate medicine. However, whether such meetings can uphold the integrity of decision-making processes has yet to be explored. This narrative review aimed to summarize the literature on decision making in virtual teams, discuss ways to improve the effectiveness of virtual teams, and explore their implications for practice. METHODS: In August 2017, the Web of Science platform was searched with the terms 'decision making' AND 'virtual teams' for articles published within the last 20 years. The search yielded 336 articles, which was narrowed down to a final set of 188 articles. A subset of these, subjectively deemed to be of high-quality and relevant to the work of promotions committees, was included in this review. RESULTS: Virtual team functioning was explored with respect to team composition and development, idea generation and selection, group memory, and communication. While virtual teams were found to potentially offer a number of key benefits over face-to-face meetings including convenience and scheduling flexibility, inclusion of members at remote sites, and enhanced idea generation and external storage, these benefits must be carefully weighed against potential challenges involving planning and coordination, integration of perspectives, and relational conflict among members, all of which can potentially reduce decision-making quality. DISCUSSION: Avenues to address these issues and maximize the outcomes of virtual promotions meetings are offered in light of the evidence. PMID- 29797288 TI - Emergency Department influenza vaccination campaign allows increasing influenza vaccination coverage without disrupting time interval quality indicators. AB - To evaluate the impact of an influenza vaccination (IV) coverage (IVC) in a vaccination campaign of an Emergency Department (EDVC) and its impact on ED time interval quality indicators. We conducted a 4 year observational study, with an intervention during the 4th year. IVC was calculated during pre-and early epidemic periods. During the final period, a 12 weeks EDVC was implemented. Physicians and nurses were trained and sensitized in the importance of vaccination, and their role in the prevention of severe forms of influenza was reinforced. The vaccine was proposed by physicians and nurses, and delivered by them. Repeated measures ANOVA is a validated method for related not independent groups ( https://statistics.laerd.com/statistical-guides/repeated-measures-anova statistical-guide.php ). Overall, IVC was 987/3191 (30.9%) with an increasing trend from 28.8 to 33.2%. In the fourth period, out of 868 patients identified with IV indication, 288 had already been vaccinated (IVC 33.2%). After excluding patients presenting criteria of exclusion, IV was proposed to 475 patients: 317 (66.7%) accepted. The vaccination rate after patient's acceptance was 89.6% (288/317). At the end of the EDVC, influenza vaccination coverage was 572 (284 + 288)/868 (65.9%). The delay between arrival at the ED and seeing the triage nurse and physician as well as the overall ED length of stay were not modified during the study period and before and during EDVC. EDVC effectively doubled the influenza vaccination coverage, without modifying ED time interval quality indicators. PMID- 29797290 TI - Diagnostic accuracy of diffusion weighted imaging for differentiation of supratentorial pilocytic astrocytoma and pleomorphic xanthoastrocytoma. AB - PURPOSE: Supratentorial pilocytic astrocytoma (PA) may mimic pleomorphic xanthoastrocytoma (PXA) on conventional MR imaging, and a differentiation is clinically important because of distinct recurrence rate and anaplastic transformation rate. The purpose of this study was to investigate the diagnostic potential of diffusion-weighted imaging (DWI) in differentiating supratentorial PA from PXA. METHODS: We retrospectively reviewed DWI and conventional MR imaging of 16 patients with supratentorial PA and 8 patients with PXA. Variables of mean ADC values (ADCmean) and minimum ADC values (ADCmin) were calculated from the ROIs containing the contrast-enhancing lesion on DWI. ADCmean values and ADCmin values were compared among all supratentorial PA and PXA as well as between the subgroup of lobar PA and PXA by using an unpaired Student's t test. The optimum threshold, sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Both ADCmean values (1542 +/- 186 vs 1084 +/- 201 * 10-6 mm2/s; P < 0.001) and ADCmin values (1355 +/- 183 vs 988 +/- 180 * 10-6 mm2/s; P < 0.001) were significantly higher in supratentorial PA compared with PXA. The ADCmean values and ADCmin values were also significantly higher in lobar PA than those in PXA. The ADCmean values were useful for differentiating supratentorial PA from PXA, with a threshold value of > 1189.8 * 10-6 mm2/s (sensitivity, 93.8%; specificity, 100%). The optimal threshold values of > 1189.8 * 10-6 mm2/s for ADCmean values provide sensitivity and specificity of 85.7 and 100%, respectively, for discriminating lobar PA from PXA. The optimum threshold value for ADCmin was > 1063.5 * 10-6 mm2/s. CONCLUSION: DWI is helpful in characterization and differentiation of supratentorial PA from PXA. PMID- 29797291 TI - Dynamic of VE-cadherin-mediated spermatid-Sertoli cell contacts in the mouse seminiferous epithelium. AB - Spermatids are haploid differentiating cells that, in the meantime they differentiate, translocate along the seminiferous epithelium towards the tubule lumen to be just released as spermatozoa. The success of such a migration depends on dynamic of spermatid-Sertoli cell contacts, the molecular nature of which has not been well defined yet. It was demonstrated that the vascular endothelial cadherin (VEC) is expressed transitorily in the mouse seminiferous epithelium. Here, we evaluated the pattern of VEC expression by immunohistochemistry first in seminiferous tubules at different stages of the epithelial cycle when only unique types of germ cell associations are present. Changes in the pattern of VEC localization according to the step of spermatid differentiation were analysed in detail using testis fragments and spontaneously released germ cells. Utilizing the first wave of spermatogenesis as an in vivo model to have at disposal spermatids at progressive steps of differentiation, we checked for level of looser VEC association with the membrane by performing protein solubilisation under mild detergent conditions and assays through VEC-immunoblotting. Being changes in VEC solubilisation paralleled in changes in phosphotyrosine (pY) content, we evaluated if spermatid VEC undergoes Y658 phosphorylation and if this correlates with VEC solubilisation and spermatid progression in differentiation. Altogether, our study shows a temporally restricted pattern of VEC expression that culminates with the presence of round spermatids to progressively decrease starting from spermatid elongation. Conversely, pY658-VEC signs elongating spermatids; its intracellular polarized compartmentalization suggests a possible involvement of pY658-VEC in the acquisition of spermatid cell polarity. PMID- 29797292 TI - Telemedicine in Complex Diabetes Management. AB - PURPOSE OF REVIEW: Telehealth has the potential to positively transform the quality and cost-effectiveness of complex diabetes management in adults. This review explores the landscape of telemedicine approaches and evidence for incorporation into general practice. RECENT FINDINGS: Telemedicine for diabetes care is feasible based on over 100 randomized clinical trials. Evidence shows modest benefits in A1c lowering and other clinical outcomes that are better sustained over time vs. usual care. While telemedicine interventions are likely cost-effective in diabetes care, more research is needed using implementation science approaches. Telehealth platforms have been shown to be both feasible and effective for health care delivery in diabetes, although there are many caveats that require tailoring to the institution, clinician, and patient population. Research in diabetes telehealth should focus next on how to increase access to patients who are known to be marginalized from traditional models of health care. PMID- 29797293 TI - The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration. AB - The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil(r) suspension, two doses), SB705498 (weak base, tablets vs. capsules), cyclosporine A (Sandimmun(r) vs. Sandimmun(r) Neoral), nifedipine (Adalat(r) capsule vs. Macorel(r) tablet), and itraconazole (Sporanox(r) capsule vs. Sporanox(r) solution). AUC0-0.75h values were calculated from the apparent concentration versus time data in the duodenal compartment of the BioGIT system. Differences in AUC0-0.75h values were evaluated versus differences in AUC0-1h and in AUC0-2h values calculated from previously collected plasma data in healthy adults. Ratios of mean AUC0-0.75h, mean AUC0-1h, and mean AUC0-2h values were estimated using the lowest dose or the formulation with the lower AUC0-0.75h value as denominator. The BioGIT system qualitatively identified the impact of dose and of formulation on early exposure in all cases. Log-transformed mean BioGIT AUC0-0.75h ratios correlated significantly with log-transformed mean plasma AUC0-1h ratios. Based on this correlation, BioGIT AUC0-0.75h ratios between 0.3 and 10 directly reflect corresponding plasma AUC0-1h ratios. BioGIT system is a valuable tool for the assessment of the impact of dose and formulation on early exposure to low solubility drugs. PMID- 29797294 TI - The effect of inhibition on the existence of traveling wave solutions for a neural field model of human seizure termination. AB - In this paper we study the influence of inhibition on an activity-based neural field model consisting of an excitatory population with a linear adaptation term that directly regulates the activity of the excitatory population. Such a model has been used to replicate traveling wave data as observed in high density local field potential recordings (Gonzalez-Ramirez et al. PLoS Computational Biology, 11(2), e1004065, 2015). In this work, we show that by adding an inhibitory population to this model we can still replicate wave properties as observed in human clinical data preceding seizure termination, but the parameter range over which such waves exist becomes more restricted. This restriction depends on the strength of the inhibition and the timescale at which the inhibition acts. In particular, if inhibition acts on a slower timescale relative to excitation then it is possible to still replicate traveling wave patterns as observed in the clinical data even with a relatively strong effect of inhibition. However, if inhibition acts on the same timescale as the excitation, or faster, then traveling wave patterns with the desired characteristics cease to exist when the inhibition becomes sufficiently strong. PMID- 29797295 TI - Enhanced Production of Crude Violacein from Glucose in Escherichia coli by Overexpression of Rate-Limiting Key Enzyme(S) Involved in Violacein Biosynthesis. AB - Crude violacein, consisting of violacein and deoxyviolacein, displays many attractive bio-activities in the field of drug therapy. To produce crude violacein from an industrially economic carbon source, we firstly introduced the violacein pathway into Escherichia coli B8/pTRPH1, which was previously engineered to accumulate tryptophan from glucose. A crude violacein production capacity of 0.25 g L-1 OD600-1 was obtained using glucose-containing medium. By further overexpressing each of the five genes involved in violacein synthesis pathway, VioE was found as the rate-limiting step for the violacein production. The optimal strain of B8/pTRPH1-pVio-VioE was then used for fed-batch fermentation in a 5-L bioreactor and a crude violacein titer of 4.45 g L-1, as well as a productivity of 98.7 mg L-1 h-1, was obtained. This engineered strain showed the highest violacein titer and productivity reported so far. Our optimal strain of E. coli B8/pTRPH1-pVio-VioE by overexpression of the rate-limiting VioE in violacein synthesis pathway was a potential violacein producer by directly using glucose for industrial application. PMID- 29797296 TI - Calcium Alginate Bead-mediated Enhancement of the Selective Recovery of a Lead Novel Antifungal Bacillomycin Variant. AB - In the pursuit of new antifungal compounds, five coproduced lipopeptide variants (AF1 to AF5) from wild-type Bacillus subtilis RLID 12.1 were identified in our previous study. Out of five, AF4 was identified as a novel lead molecule belonging to the bacillomycin family showing less cytotoxicity at its respective minimum inhibitory concentrations (MIC) evaluated against 81 strains of Candida and Cryptococcus species (including clinical isolates); besides this, AF4 purified in the present study exhibited encouraging MIC values against 10 clinical mycelial fungi. Aiming for a selective production augmentation of AF4 lipopeptide variant, a new fermentation media comprising malt extract (1.01%), dextrose (0.55%), peptone (1.79%), MnSO4 (2 mM), and NaCl (0.5%) was formulated. Maximum production of 954.8 +/- 10.8 mg/L was achieved with 44% selectivity at 30 degrees C compared to unoptimized conditions (186.4 +/- 6.1 mg/L). Use of calcium alginate beads in the formulated media during the onset of lipopeptide production resulted in an augmentation in the selectivity of the most efficacious AF4 variant to about 72% presumably due to attenuation of other coproduced lipopeptide variants AF1 and AF2. Difference in yield of lipopeptides varied with bead size, bead preparation ratios, and sodium alginate concentrations. Use of Ca alginate beads in the upstream production process of the lead AF4 variant may be considered as a novel strategy to address the potential challenge that may arise during the scale-up and downstream processing steps. Another significant finding derived from the study is that the proportion of bacillomycin variants of B. subtilis RLID 12.1 could be controlled by temperature and metal ions under static and shaking conditions. PMID- 29797297 TI - Correlation Between Size and Activity Enhancement of Recombinantly Assembled Cellulosomes. AB - As multienzyme complexes, cellulosomes hydrolyze cellulosic biomass with high efficiency, which is believed to be attributed to either one or both factors: (1) synergy among the catalytic and substrate-binding entities and (2) the large size of cellulosome complexes. Although the former factor has been extensively documented, the correlation between size and specific activity of cellulosomes is still elusive to date. In this study, primary and secondary scaffoldins with 1, 3, or 5 copies of type I/II cohesin domains were recombinantly synthesized and various cellulosomes carrying 1, 3, 5, 9, 15, or 25 molecules of cellulase mixtures of family 5, 9, and 48 glycoside hydrolases were assembled. In addition, the assembled complex was annexed to cellulose with the aid of a family 3a carbohydrate-binding module (CBM3a). Measuring cellulolytic hydrolysis activities of assembled cellulosomes on crystalline Avicel revealed that higher degree of cellulosome complexity resulted in more efficient cellulose hydrolysis with plateaued synergic effects after the cellulosome size reaches certain degree. PMID- 29797299 TI - Schizosaccharomyces pombe as an Efficient Yeast to Convert Sugarcane Bagasse Pretreated with Ionic Liquids in Ethanol. AB - Pretreatment of lignocellulosic biomass with ionic liquids (ILs) has been extensively studied, being regarded as one of the most promising methods for obtaining fermentable sugars. In this research, it was investigated the production of ethanol from sugars released from sugarcane bagasse pretreated with the ionic liquids [C4mim][OAc] and [C2mim][OAc], hydrolysed with Penicillium echinulatum enzymes and using Saccharomyces cerevisiae and Schizosaccharomyces pombe. Yields of about 43 and 56% of ethanol were observed for S. cerevisiae and biomass pretreated with [C2mim][OAc] and [C4mim][OAc], respectively. S. pombe yielded 52 and 78% ethanol for [C2mim][OAc] and [C4mim][OAc], respectively. These results indicate that S. pombe showed best performance for alcoholic fermentation from sugars released from pretreated biomass by ILs. PMID- 29797301 TI - Cost-Effectiveness Analysis of Intracapsular Tonsillectomy and Total Tonsillectomy for Pediatric Obstructive Sleep Apnea. AB - PURPOSE: We performed an economic evaluation using a decision-tree model to analyze the relative cost effectiveness from the United States Centers for Medicare and Medicaid Services (CMS) perspective of two different methods of tonsillectomy (traditional total tonsillectomy and partial intracapsular) for pediatric obstructive sleep apnea (OSA). MATERIALS AND METHODS: Procedural costs were drawn from published literature and Medicare values. Effectiveness and probabilities were drawn from medical literature. Primary intervention was monopolar-technique total tonsillectomy or microdebrider-assisted partial intracapsular tonsillectomy. Secondary interventions included operative control of hemorrhage, treatment of severe dehydration, or revision tonsillectomy. The decision model starts with pediatric patients with OSA, choosing between total and partial tonsillectomy. Outcomes were measured by costs (US dollars), effectiveness [quality-adjusted life year (QALY)], and a willingness-to-pay threshold of US$100,000/QALY. Base case analysis, probabilistic sensitivity analysis (PSA) and deterministic sensitivity analyses were performed. Primary outcome was incremental cost-effectiveness ratio (ICER) for each of the two tonsillectomy techniques. RESULTS: Base case analysis demonstrated that total tonsillectomy was more cost effective at US$12,453.40 per QALY gained. In PSA, 82.84% of the simulations show total tonsillectomy to be the more cost-effective strategy. Deterministic sensitivity analyses showed that when the rate of OSA recurrence is lower than 3.12%, partial tonsillectomy would be more cost effective. When the failure rate of partial tonsillectomy is below 1.0%, it is more cost effective even when total tonsillectomy is 100% successful. CONCLUSION: Study results suggest that overall monopolar-technique total tonsillectomy is more cost effective. However, with varying adjustments for disutility caused by procedural complications, intracapsular tonsillectomy could become a more cost effective technique for treating pediatric OSA. PMID- 29797300 TI - Biological Response of Osteoblastic and Chondrogenic Cells to Graphene-Containing PCL/Bioactive Glass Bilayered Scaffolds for Osteochondral Tissue Engineering Applications. AB - Graphene-containing 13-93 bioactive glass and poly(epsilon-caprolactone)-based bilayer, electrically conductive scaffolds were prepared for osteochondral tissue repair. Biological response of osteoblastic MC3T3-E1 and chondrogenic ATDC5 cells to the composite scaffolds was assessed under mono-culture and co-culture conditions. Cytotoxicity was investigated using MTT assay, cartilage matrix production was evaluated by Alcian blue staining, and mineralization of both types of cells in the different culture systems was observed by Alizarin red S staining. Results showed that osteoblastic and chondrogenic cells utilized in the study did not show toxic response to the prepared scaffolds under mono-culture conditions and higher cell viability rates were obtained in co-culture conditions. Larger mineralized areas were determined under co-culture conditions and calcium deposition amount significantly increased compared with that in control group samples after 21 days. Additionally, the amount of glycosaminoglycans synthesized in co-culture was higher compared to mono-culture conditions. Electric stimulation applied under mono-culture conditions suppressed the viability of MC3T3-E1 cells whereas it enhanced the viability rates of ATDC5 cells. The study suggests that the designed bilayered osteochondral constructs have the potential for osteochondral defect repair. PMID- 29797298 TI - Activity Essential Residue Analysis of Taxoid 10beta-O-Acetyl Transferase for Enzymatic Synthesis of Baccatin. AB - Taxoid 10beta-O-acetyl transferase (DBAT) is a key enzyme in the biosynthesis of the famous anticancer drug paclitaxel, which catalyses the formation of baccatin III from 10-deacetylbaccatin III (10-DAB). However, the activity essential residues of the enzyme are still unknown, and the acylation mechanism from its natural substrate 10-deacetylbaccatin III and acetyl CoA to baccatin III remains unclear. In this study, the homology modelling, molecular docking, site-directed mutagenesis, and kinetic parameter determination of the enzyme were carried out. The results showed that the enzyme mutant DBATH162A resulted in complete loss of enzymatic activity, suggesting that the residue histidine at 162 was essential to DBAT activity. Residues D166 and R363 which were located in the pocket of the enzyme by homology modelling and molecular docking were also important for DBAT activity through the site-directed mutations. Furthermore, four amino acid residues including S31 and D34 from motif SXXD, D372 and G376 from motif DFGWG also played important roles on acylation. This was the first report of the elucidation of the activity essential residues of DBAT, making it possible for the further structural-based re-design of the enzyme for efficient biotransformation of baccatin III and paclitaxel. PMID- 29797303 TI - Erratum to: Total Knee Arthroplasty versus Osteochondral Allograft: Prevalence and Risk Factors following Tibial Plateau Fractures. PMID- 29797304 TI - Novel Colloidal Microstructures of beta-Escin and the Liposomal Components Cholesterol and DPPC. AB - The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaja saponaria with cholesterol and a phospholipid opened up new avenues for the development of drug delivery systems for vaccine application with additional adjuvant properties. In this study, beta-escin, a monodesmosidic triterpene saponin from horse chestnut, was investigated in terms of its interaction with liposomal components (cholesterol, dipalmitoylphosphatidylcholine) by Langmuir film balance studies and with regard to particle formation visualized by transmission electron microscopy. A strong interaction of beta-escin with cholesterol was observed by Langmuir isotherms due to the intercalation of the saponin into the monolayer, whereas no interaction occurred with dipalmitoylphosphatidylcholine. Transmission electron microscopy studies also confirmed the strong interaction of beta-escin with cholesterol. In aqueous pseudo-ternary systems (beta-escin, dipalmitoylphosphatidylcholine, cholesterol) and in pseudo-binary systems (beta-escin, cholesterol), new colloidal structures built up from ring-like and worm-like subunits were observed with a size of about 100 - 200 nm. These colloidal structures are formed in pseudo-binary systems by aggregation of the subunits, whereas in pseudo-ternary systems, they are formed among others by attacking the liposomal membrane. The rehydration of the liposomal dispersions in NANOpure water or Tris buffer pH 7.4 (140 mM) resulted in the same particle formation. In contrast, the sequence of the dispersions' production process affected the particle formation. Unless adding the saponin to the other components from the beginning, just a liposomal dispersion was formed without any colloidal aggregates of the subunits mentioned above. PMID- 29797305 TI - Ethnobotany and Medicinal Plant Biotechnology: From Tradition to Modern Aspects of Drug Development. AB - Secondary natural products from plants are important drug leads for the development of new drug candidates for rational clinical therapy and exhibit a variety of biological activities in experimental pharmacology and serve as structural template in medicinal chemistry. The exploration of plants and discovery of natural compounds based on ethnopharmacology in combination with high sophisticated analytics is still today an important drug discovery to characterize and validate potential leads. Due to structural complexity, low abundance in biological material, and high costs in chemical synthesis, alternative ways in production like plant cell cultures, heterologous biosynthesis, and synthetic biotechnology are applied. The basis for any biotechnological process is deep knowledge in genetic regulation of pathways and protein expression with regard to todays "omics" technologies. The high number genetic techniques allowed the implementation of combinatorial biosynthesis and wide genome sequencing. Consequently, genetics allowed functional expression of biosynthetic cascades from plants and to reconstitute low-performing pathways in more productive heterologous microorganisms. Thus, de novo biosynthesis in heterologous hosts requires fundamental understanding of pathway reconstruction and multitude of genes in a foreign organism. Here, actual concepts and strategies are discussed for pathway reconstruction and genome sequencing techniques cloning tools to bridge the gap between ethnopharmaceutical drug discovery to industrial biotechnology. PMID- 29797306 TI - Identification of a Collagenase-Inhibiting Flavonoid from Alchemilla vulgaris Using NMR-Based Metabolomics. AB - This paper describes the use of 1H NMR profiling and chemometrics in order to facilitate the selection of medicinal plants as potential sources of collagenase inhibitors. A total of 49 plants with reported ethnobotanical uses, such as the healing of wounds and burns, treatment of skin-related diseases, rheumatism, arthritis, and bone diseases, were initially chosen as potential candidates. The in vitro collagenase inhibitory activity of hydroalcoholic extracts of these plants was tested. Moreover, their phytochemical profiles were analyzed by 1H NMR and combined with the inhibitory activity data by an orthogonal partial least squares model. The results showed a correlation between the bioactivity and the concentration of phenolics, including flavonoids, phenylpropanoids, and tannins, in the extracts. Considering the eventual false-positive effect on the bioactivity given by tannins, a tannin removal procedure was performed on the most active extracts. After this procedure, Alchemilla vulgaris was the most persistently active, proving to owe its activity to compounds other than tannins. Thus, this plant was selected as the most promising and further investigated through bioassay-guided fractionation, which resulted in the isolation of a flavonoid, quercetin-3-O-beta-glucuronide, as confirmed by NMR and HRMS spectra. This compound showed not only a higher activity than other flavonoids with the same aglycone moiety, but was also higher than doxycycline (positive control), the only Federal Drug Administration-approved collagenase inhibitor. The approach employed in this study, namely the integration of metabolomics and bioactivity guided fractionation, showed great potential as a tool for plant selection and identification of bioactive compounds in natural product research. PMID- 29797308 TI - Comparison of Current Swiss Fetal Biometry Reference Charts with Reference Charts from 1999. Are Fetuses Getting Bigger? AB - PURPOSE: To create current fetal biometry reference ranges and to compare them with references published in 1999, from the same local area in order to generate data for secular trend in fetal size. MATERIALS AND METHODS: Applying the same methodology as previously published, we calculated reference ranges for biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), abdominal circumference (AC) and femur length (FL) in 7863 patients examined at the obstetric clinics in a cross-sectional, prospective study in a university setting from January 2008 to December 2014. In order to compare the new reference ranges with our previously published data, we used Z-Scores and displayed the pick-up of fetal biometry data below the 5th and above the 95th percentile using the previously published reference charts. RESULTS: The comparison of the charts showed a minimal but clinically relevant increase in mean fetal body measures (BPD, HC, AC). Applying the 1999 charts to the new dataset, we would classify only 162 of 339 fetuses (47.8 %) to be correctly below the 5th percentile for AC and only 134 of 349 (38.4 %) fetuses were correctly below the 5th percentile for HC. On the other hand, the 1999 charts classified 426 instead of 332 fetuses to be above the 95th percentile for AC, which means an overestimation of 28.3 %. CONCLUSION: Applying a similar methodology, study collective and clinical setting, our new charts showed clinically relevant differences compared to the 1999 charts. The data suggest that within one generation fetuses are getting bigger and regular updates of fetal reference charts are needed. PMID- 29797307 TI - Validation of Multiparametric Ultrasonography Criteria with Digital Subtraction Angiography in Carotid Artery Disease: A Prospective Multicenter Study. AB - PURPOSE: The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. MATERIALS AND METHODS: We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. RESULTS: A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. CONCLUSION: At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease. PMID- 29797309 TI - Eosinophilic fasciitis and lichen sclerosus in a patient treated with nivolumab. PMID- 29797310 TI - Targeted mutation screening of 292 candidate genes in 38 children with inborn haematological cytopenias efficiently identifies novel disease-causing mutations. AB - Establishing a precise diagnosis is essential in inborn haematological cytopenias to enable appropriate treatment decisions and avoid secondary organ damage. However, both diversity and phenotypic overlap of distinct disease entities may make the identification of underlying genetic aetiologies by classical Sanger sequencing challenging. Instead of exome sequencing, we established a systematic next generation sequencing-based panel targeting 292 candidate genes and screened 38 consecutive patients for disease-associated mutations. Efficient identification of the underlying genetic cause in 17 patients (44.7%), including 13 novel mutations, demonstrates that this approach is time- and cost-efficient, enabling optimal management and genetic counselling. PMID- 29797311 TI - The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction. AB - BACKGROUND AND PURPOSE: Platelet activation provides a critical link between inflammation and thrombosis. Sulforaphane (SFN), a naturally occurring isothiocyanate, has been shown to display both anti-inflammatory and anti thrombotic actions in the systemic microvasculature. As inflammation promotes thrombosis and vice versa, in this study we investigated whether SFN is able to reduce inflammatory potentiation of thrombotic events, suppress platelet activation and thrombus formation in the cerebral microvasculature. EXPERIMENTAL APPROACH: Thrombosis was induced in the murine brain using the light/dye-injury model, in conjunction with LPS treatment, with and without SFN treatment. In vitro and in vivo platelet assays (aggregation, flow and other functional tests) were also employed, using both human and murine platelets. KEY RESULTS: SFN was found to reduce LPS-mediated enhancement of thrombus formation in the cerebral microcirculation. In tail-bleed experiments, LPS treatment prolonged bleeding time, and SFN treatment was found to protect against this LPS-induced derangement of platelet function. SFN inhibited collagen-mediated platelet aggregation in vitro and in vivo and the associated adhesion and impaired calcium signalling. Furthermore, glycoprotein VI was shown to be involved in the protective effects observed with SFN treatment. CONCLUSIONS AND IMPLICATIONS: The data presented here provide evidence for the use of SFN in preventing stroke in selected high risk patient cohorts. PMID- 29797312 TI - A prospective observational study of pigmented naevi changes in psoriasis patients on biologic therapy. AB - BACKGROUND/OBJECTIVES: Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. METHODS: Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography. The mean follow-up period was 1.5 years. RESULTS: The study and control patients had comparable age, gender, previous and family history of non-melanoma skin cancers and melanomas, as well as previous sun exposure and total number of naevi. The number of naevi with major dermoscopic changes was 3% in the study and 1.9% in the control group, with an adjusted incidence rate ratio of 1.45 (95% confidence interval 0.90-2.33; P = 0.125). The rate of minor changes was 15.9% in the study group versus 19.4% in the control (adjusted incidence rate ratio 0.77, 95% confidence interval 0.57-1.08; P = 0.14). There were six new dysplastic naevi in 4/45 biologic patients and four in 4/43 controls; however, the difference was not significant (relative risk 0.96, 95% confidence interval -0.12 to 0.12; P = 0.95). There were no melanomas in either group. CONCLUSION: Over a mean follow-up period of 1.5 years there was no evidence of significantly different changes in naevi or development of new dysplastic naevi in psoriasis patients on biologic treatment compared to controls. PMID- 29797313 TI - Patterns of RSA and observed distress during the still-face paradigm predict later attachment, compliance and behavior problems: A person-centered approach. AB - This study examined profiles of infant observed distress and physiological regulation indexed by respiratory sinus arrhythmia (RSA) levels during the still face paradigm at 6 months using a person-centered approach. Mothers and infants (N = 206) participated in the study when infants were 6 months, 1 year, and 2 years old. Attachment was assessed at 1 year via the Strange Situation. Children's compliance behaviors were assessed at 2 years during a toy clean-up task. Mothers reported children's behavior problems at 4.5 years. Latent profile analysis yielded four profiles: highly distressed, but regulating; over regulated; resilient to distress; and under-regulated. Infants in the "resilient to distress" profile characterized by high RSA levels and low negative affect exhibited the most adaptive outcomes such as lower attachment avoidance, higher compliance, and lower behavior problems. Therefore, this study highlights the importance of considering patterns of behavioral and physiological indicators of infant emotionality together for understanding adaptive functioning. PMID- 29797314 TI - Physicians' Views on Advance Care Planning and End-of-Life Care Conversations. AB - OBJECTIVES: To evaluate physicians' views on advance care planning, goals of care, and end-of-life conversations. DESIGN: Random sample telephone survey. SETTING: United States. PARTICIPANTS: Physicians (primary care specialists; pulmonology, cardiology, oncology subspecialists) actively practicing medicine and regularly seeing patients aged 65 and older (N=736; 81% male, 75% white, 66% aged >=50. MEASUREMENTS: A 37-item telephone survey constructed by a professional polling group with national expert oversight measured attitudes and perceptions of barriers and facilitators to advance care planning. Summative data are presented here. RESULTS: Ninety-nine percent of participants agreed that it is important to have end-of-life conversations, yet only 29% reported that they have formal training for such conversations. Those most likely to have training included younger physicians and those caring for a racially and ethnically diverse population. Patient values and preferences were the strongest motivating factors in having advance care planning conversations, with 92% of participants rating it extremely important. Ninety-five percent of participants reported that they supported a new Medicare fee-for-service benefit reimbursing advance care planning. The biggest barrier mentioned was time availability. Other barriers included not wanting a patient to give up hope and feeling uncomfortable. CONCLUSION: With more than half of physicians reporting that they feel educationally unprepared, there medical school curricula need to be strengthened to ensure readiness for end-of-life conversations. Clinician barriers need to be addressed to meet the needs of older adults and families. Policies that focus on payment for quality should be evaluated at regular intervals to monitor their effect on advance care planning. PMID- 29797315 TI - A significant proportion of children of African descent with HbSbeta0 thalassaemia are inaccurately diagnosed based on phenotypic analyses alone. PMID- 29797316 TI - Experimental evidence of spatial signatures of approaching regime shifts in macroalgal canopies. AB - Developing early warning signals to predict regime shifts in ecosystems is a central issue in current ecological research. While there are many studies addressing temporal early warning indicators, research into spatial indicators is far behind, with field experiments even more rare. Here, we tested the performance of spatial early warning signals in an intertidal macroalgal system, where removal of algal canopies pushed the system toward a tipping point (corresponding to approximately 75% of canopy loss), marking the transition between a canopy- to a turf-dominated state. We performed a two-year experiment where spatial early warning indicators were assessed in transects where the canopy was differentially removed (from 0 to 100%). Unlike Moran correlation coefficient at lag-1, spatial variance, skewness, and spatial spectra at low frequency increased along the gradient of canopy degradation and dropped, or did not show any further increase beyond the transition point from a canopy- to a turf-dominated state (100% canopy removal). Our study provides direct evidence of the suitability of spatial early warning signals to anticipate regime shifts in natural ecosystems, emphasizing the importance of field experiments as a powerful tool to establish causal relationships between environmental stressors and early warning indicators. PMID- 29797317 TI - Light harvesting control in plants. AB - In 1991, my colleagues and I published a hypothesis article that proposed a mechanism that controls light harvesting in plants and protects them against photodamage. The major light harvesting complex, LHCII, was suggested to undergo aggregation upon exposure of the plant to damaging levels of light. Aggregated LHCII was found to be much less efficient in light harvesting, as it promptly dissipated absorbed energy into heat, possessing a very low chlorophyll fluorescence yield. Nonphotochemical quenching (NPQ) is a term coined to describe this reduction in chlorophyll fluorescence yield. This article is a story of how the hypothesis that LHCII aggregation is involved in NPQ is developed into a model that is now becoming broadly accepted by the research community. PMID- 29797318 TI - Isolation-induced ultrasonic vocalizations in pups: A comparison between Long Evans, Sprague-Dawley, and Wistar rats. AB - Rat pup ultrasonic vocalizations (USV) are usually studied in outbred rats belonging to either Long-Evans, Sprague-Dawley, or Wistar stocks, but these were not compared so far. We therefore performed a stock comparison and analyzed USV of male pups (postnatal day 11) belonging to these three stocks. Pups of all three stocks showed substantial isolation-induced USV, but differed in various call features, like call numbers, peak frequency, and frequency modulation. Also, three different call types were identified by means of a quantitative approach based on peak frequency and frequency modulation, and it was found that their proportions differed between stocks. These results are discussed with respect to functional aspects of pup USV. PMID- 29797319 TI - Robotic-assisted surgical procedures are the future of gynaecology in Australasia. PMID- 29797320 TI - The prevalence and morphological characteristics of the knee anterolateral ligament in a Chinese population. AB - The anterolateral ligament, a distinct structure connecting the lateral femoral epicondyle to the anterolateral proximal tibia, is gaining attention because of its possible function in ensuring internal rotational stability of the tibia. To study the prevalence and precise anatomical characteristics of the anterolateral ligament and its relationship to adjacent structures in a Chinese population, a total of 20 amputated knee specimens were collected. The anterolateral regions of the knees underwent detailed surgical dissection, followed by precise measurement of the anterolateral ligament and its adjacent structures. Histological analysis of the anterolateral ligament was performed using hematoxylin and eosin (H&E) staining. A thin soft tissue deep to the iliotibial band running obliquely across the lateral fibula ligament and connecting the lateral head of the gastrocnemius with the tibia, termed the 'gastrocnemius-tibial ligament' or superficial layer of the anterolateral ligament, was observed in 18 of the 20 specimens, corresponding to a prevalence of 90%. Furthermore, a well-defined anterolateral ligament deep to the gastrocnemius-tibial ligament and distinct from the lateral fibula ligament was found in all 20 knees (prevalence, 100%). The independent gastrocnemius-tibial ligament and anterolateral ligament had separate femoral originations at the lateral head of the gastrocnemius and the lateral femoral epicondyle, and the same osseous tibial insertion at the midpoint between Gerdy's tubercle and the most lateral aspect of the fibular head. H&E staining showed that both the anterolateral ligament and gastrocnemius-tibial ligament were ligaments consisting of collagenous bundles. In the Chinese Han population, the gastrocnemius-tibial ligament and anterolateral ligament may form a complex at the anterolateral aspect of the knee, which is likely involved in ensuring the internal rotational stability of the tibia. PMID- 29797321 TI - Sequence analysis of exon 1 of the ferritin light chain (FTL) gene can reveal the rare disorder 'hereditary hyperferritinaemia without cataracts'. PMID- 29797322 TI - Jussara berry (Euterpe edulis M.) oil-in-water emulsions are highly stable: the role of natural antioxidants in the fruit oil. AB - BACKGROUND: Antioxidants help prevent lipid oxidation, and therefore are critical to maintain sensory quality and chemical characteristics of edible oils. Jussara berry (Euterpe edulis M.) oil is a source of minor compounds with potential antioxidant activity. The aim of this work was to investigate the role of such compounds on the effectiveness to prevent or delay oxidation of oil present in oil-in-water emulsions, and how the emulsions' physical stability would be affected. RESULTS: Jussara berry oil extracted by ethanol extraction, its stripped variations (partially stripped, highly stripped and highly stripped with added butylhydroxytoluene), and expeller-pressed oil were used to prepare oil-in water emulsions. Jussara berry oils were analyzed before emulsions preparation to ensure their initial quality and composition, and oil-in-water emulsions were analyzed regarding their oxidative and physical stability. Ethanol extracted oil emulsion presented higher oxidative stability than highly stripped oil emulsion with added synthetic antioxidant butylahydroxytoluene (oxidative stability index 45% lower, after 60 days, and reached undetectable levels after 90 days). All emulsions remained physically stable for up to 120 days of storage. CONCLUSION: Our results indicate that natural antioxidants in jussara berry oil protect emulsions from oxidation while keeping physical stability unchanged. (c) 2018 Society of Chemical Industry. PMID- 29797324 TI - Effect of university students' sedentary behavior on stress, anxiety, and depression. AB - PURPOSE: We identified the effect of sedentary behavior on stress, anxiety, and depression among Korean university students. DESIGN AND METHODS: Data were collected from 244 students using self-reported sitting time, the Perceived Stress Scale, the Beck Anxiety Inventory, and the Center for Epidemiological Studies-Depression Scale. FINDINGS: Mean sitting time was 7.96 h per day. As sitting hours increased, university students' stress, anxiety, and depression significantly increased despite controlling for sex, economic level, body mass index, underlying disease, and health self-management. PRACTICAL IMPLICATIONS: Intervention programs that reduce sedentary behavior and improve physical activity and mental health for university students are necessary. PMID- 29797323 TI - Effects of Ascophyllum nodosum seaweed extracts on lettuce growth, physiology and fresh-cut salad storage under potassium deficiency. AB - BACKGROUND: Potassium (K) deficiency in leafy vegetables such as lettuce is a major concern regarding quality. Seaweed (SW) extracts, as biostimulants, are biodegradable materials and have become increasingly popular as they are reported to enhance crop growth and yield. RESULTS: In order to overcome K deficiencies (i.e. 375 vs 125 mg L-1 ), alternative foliar applications with extracts of Ascophyllum nodosum SW or K were examined using lettuce plants which were grown hydroponically. Potassium deficiency (at 125 mg L-1 ) reduced plant biomass, photosynthetic rate, leaf stomatal conductance, lettuce potassium content and tissue antioxidant capacity as compared with the higher K level (375 mg L-1 ). Application of SW increased the relative growth of lettuce in the low-K treatment. The K level and/or SW application altered the plant's enzyme protective activity (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD) against oxidative stress and hydrogen peroxide (H2 O2 ) production. Spray applications of SW mitigated the effects of K deficiency on indicators of enzyme activity and plant damage, back to levels of high K content (375 mg L-1 ). The high K level, but also SW application, increased the antioxidant activity of the processed lettuce before storage. Foliar application of the SW extract increased the quality of cut lettuce grown in 125 mg L-1 K conditions by reducing the rate of respiration and increasing consumer preference. CONCLUSION: The SW application could alter the detrimental effects of K deficiency during lettuce growth and storage of processed products. (c) 2018 Society of Chemical Industry. PMID- 29797325 TI - Type 1 cryoglobulinaemia leading to gangrene of the toes and ischaemic ulceration. PMID- 29797326 TI - Treating disorganized attachment in the Group Attachment-Based Intervention (GABI(c)): A case study. AB - This paper describes the treatment of a mother and child who demonstrated disorganized attachment behaviors in their interactions with one another. The mother, who was diagnosed with Borderline Personality Disorder, felt incapable of managing her aggressive toddler and his emotional needs. The dyad was referred for therapy due to concerns about his developmental progress, evident delays having been mainly attributed to the problems observed within the parent-child relationship. The primary intervention applied to working with the dyad was the Group Attachment-Based Intervention (GABI(c)), developed by Anne Murphy in collaboration with Miriam Steele and Howard Steele. The mother also received individual psychotherapy as a supplement to the dyadic and group work of GABI(c). The process and outcome of this comprehensive approach to treating a vulnerable dyad is explored in this case study. PMID- 29797327 TI - Transcriptomic rationale for synthetic lethality-targeting ERCC1 and CDKN1A in chronic myelomonocytic leukaemia. AB - Despite the absence of mutations in the DNA repair machinery in myeloid malignancies, the advent of high-throughput sequencing and discovery of splicing and epigenetics defects in chronic myelomonocytic leukaemia (CMML) prompted us to revisit a pathogenic role for genes involved in DNA damage response. We screened for misregulated DNA repair genes by enhanced RNA-sequencing on bone marrow from a discovery cohort of 27 CMML patients and 9 controls. We validated 4 differentially expressed candidates in CMML CD34+ bone marrow selected cells and in an independent cohort of 74 CMML patients, mutationally contextualized by targeted sequencing, and assessed their transcriptional behavior in 70 myelodysplastic syndrome, 66 acute myeloid leukaemia and 25 chronic myeloid leukaemia cases. We found BAP1 and PARP1 down-regulation to be specific to CMML compared with other related disorders. Chromatin-regulator mutated cases showed decreased BAP1 dosage. We validated a significant over-expression of the double strand break-fidelity genes CDKN1A and ERCC1, independent of promoter methylation and associated with chemorefractoriness. In addition, patients bearing mutations in the splicing component SRSF2 displayed numerous aberrant splicing events in DNA repair genes, with a quantitative predominance in the single strand break pathway. Our results highlight potential targets in this disease, which currently has few therapeutic options. PMID- 29797328 TI - Mechanism of peptide absorption in the isolated forestomach epithelial cells of dairy cows. AB - BACKGROUND: Peptide absorption from the forestomach plays a vital role in protein nutrition of dairy cows. This study was conducted to investigate the mechanism of dipeptide absorption in the forestomach of dairy cows using isolated omasal epithelial cells (OECs) and ruminal epithelial cells (RECs). RESULTS: Compared with RECs, the OECs formed a less tight monolayer, but had greater ability to transport glycylsarcosine (Gly-Sar) (P < 0.05). The OEC monolayers were immunopositive for the antibodies of anti-junction proteins. Gly-Sar transport was significantly greater at 37 degrees C than that at 4 degrees C, with an optimal pH of 6.0-6.5, and was decreased significantly by diethylpyrocarbonate and dipeptide Met-Gly (P < 0.05). The apical-to-basolateral transport was significantly greater than basolateral-to-apical transport (P < 0.05). Knockdown of peptide transporter 1 (PepT1) resulted in less Gly-Sar uptake in OECs, whereas overexpression of PepT1 in OECs resulted in higher Gly-Sar uptake (P < 0.05). Additionally, the expression of PepT1 was upregulated by the treatment with various dipeptides (P < 0.05). CONCLUSION: The OECs have a greater ability to transport Gly-Sar than RECs do. Both passive and active routes are involved in the process of Gly-Sar absorption in the isolated cultured forestomach epithelial cells from dairy cows. (c) 2018 Society of Chemical Industry. PMID- 29797329 TI - Can we conserve trans-resveratrol content and antioxidant activity during industrial production of chocolate? AB - BACKGROUND: Cocoa exhibits high content of phenolic compounds, among which trans resveratrol stands out, associated with several bioactive activities such as antioxidant properties. Chocolate contains reduced amounts of these bioactive compounds due to losses during the production process. Therefore, this study aimed to assess changes in total phenolic content, and specifically trans resveratrol, as well as changes in the antioxidant activity of cocoa and its products during industrial production of chocolate. RESULTS: A total of ten different cocoa products were analyzed. The processes of fermentation and roasting caused significant loss of total phenolic compounds and antioxidant activity. The high temperature of roasting had a major influence on this loss (71% for total phenolic compounds and 53-77% for antioxidant activity), except for trans-resveratrol. The trans-resveratrol content formed after fermentation (9.8 MUg kg-1 ) showed little variation during the processes, and it was detected in higher concentrations both in natural (11.4 MUg kg-1 ) and in alkalized cocoa powder (13.5 MUg kg-1 ). Alkalization of cocoa products led to loss of capacity of deactivating superoxide radical. CONCLUSION: These findings contribute to the optimization of the production process of chocolate and other food products containing cocoa and its derivatives, aiming to better preserve their bioactive compounds. (c) 2018 Society of Chemical Industry. PMID- 29797330 TI - Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients. AB - Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+ ) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection. PMID- 29797331 TI - Comparative safety and efficacy of apixaban versus warfarin in patients with end stage renal disease: Meta-analysis. PMID- 29797332 TI - Brain size growth in wild and captive chimpanzees (Pan troglodytes). AB - Despite many studies of chimpanzee brain size growth, intraspecific variation is under-explored. Brain size data from chimpanzees of the Tai Forest and the Yerkes Primate Research Center enable a unique glimpse into brain growth variation as age at death is known for individuals, allowing cross-sectional growth curves to be estimated. Because Tai chimpanzees are from the wild but Yerkes apes are captive, potential environmental effects on neural development can also be explored. Previous research has revealed differences in growth and health between wild and captive primates, but such habitat effects have yet to be investigated for brain growth. Here, I use an iterative curve fitting procedure to estimate brain growth and regression parameters for each population, statistically comparing growth models using bootstrapped confidence intervals. Yerkes and Tai brain sizes overlap at all ages, although the sole Tai newborn is at the low end of captive neonatal variation. Growth rate and duration are statistically indistinguishable between the two populations. Resampling the Yerkes sample to match the Tai sample size and age group composition shows that ontogenetic variation in the two groups are remarkably similar despite the latter's limited size. Best fit growth curves for each sample indicate cessation of brain size growth at around 2 years, earlier than has previously been reported. The overall similarity between wild and captive chimpanzees points to the canalization of brain growth in this species. PMID- 29797333 TI - Priming to protect maize from Fusarium verticillioides and its fumonisin accumulation. AB - BACKGROUND: Systemic infection through the seed is one of the routes used by the mycotoxinogenic pathogen Fusarium verticillioides for colonizing maize plants. The prohibition of the use of most chemical fungicides by the EU has promoted research on plant resistance inducers as an effective and sustainable alternative. Induction of a priming state in maize seeds might affect their susceptibility to contamination and accumulation of fumonisins. This state by application of a natural fertilizer called Chamae on maize seeds, was investigated in two varieties to control the colonization by the fungus and the accumulation of fumonisins B1 , B2 and B3 , germinating seeds, dead plants and yield. RESULTS: After inoculation of F. verticillioides on germinating seeds, the colonization by the fungus and the accumulation of fumonisins were significantly lower in seedlings coming from treated seeds, but a significant number of plants stopped their development by necrosis. In a field trial, the 0.01% (v/v) application dilution showed a lower plant density, although the level of biomass at harvest was not affected. CONCLUSION: The priming state contributed to the control of F. verticillioides development from seed infection and fumonisin accumulation in the early stage of plant growth, without affecting the final crop yield, and could reduce fungicide use and environmental contamination. (c) 2018 Society of Chemical Industry. PMID- 29797334 TI - Pelvic mass: Schwannoma of the left seminal vesicle. AB - Schwannomas rarely occur in seminal vesicles. Here, we report a schwannoma of the left seminal vesicle. A 55-year-old man presented no clinical symptoms, and a mass in the left region of the seminal vesicle was found incidentally in a medical examination. A computed tomography and magnetic resonance imaging of pelvic were obtained and revealed a 5.17 * 2.59 * 3.5 cm mass on the left seminal vesicle. Transrectal ultrasound-guided seminal biopsy revealed a diagnosis of seminal vesical schwannoma. Laparoscopic resection of the tumour was performed. Postoperative pathology and immunohistochemical analysis revealed schwannoma arising from seminal vesical. PMID- 29797335 TI - Bayesian methods for analysis of biosimilar phase III trials. AB - A biologic is a product made from living organisms. A biosimilar is a new version of an already approved branded biologic. Regulatory guidelines recommend a totality-of-the-evidence approach with stepwise development for a new biosimilar. Initial steps for biosimilar development are (a) analytical comparisons to establish similarity in structure and function followed by (b) potential animal studies and a human pharmacokinetics/pharmacodynamics equivalence study. The last step is a phase III clinical trial to confirm similar efficacy, safety, and immunogenicity between the biosimilar and the biologic. A high degree of analytical and pharmacokinetics/pharmacodynamics similarity could provide justification for an eased statistical threshold in the phase III trial, which could then further facilitate an overall abbreviated approval process for biosimilars. Bayesian methods can help in the analysis of clinical trials, by adding proper prior information into the analysis, thereby potentially decreasing required sample size. We develop proper prior information for the analysis of a phase III trial for showing that a proposed biosimilar is similar to a reference biologic. For the reference product, we use a meta-analysis of published results to set a prior for the probability of efficacy, and we propose priors for the proposed biosimilar informed by the strength of the evidence generated in the earlier steps of the approval process. A simulation study shows that with few exceptions, the Bayesian relative risk analysis provides greater power, shorter 90% credible intervals with more than 90% frequentist coverage, and better root mean squared error. PMID- 29797336 TI - Emperipolesis and S100 expression may be seen in cutaneous xanthogranulomas: A multi-institutional observation. AB - Cutaneous Rosai-Dorfman disease (RDD) can be difficult to distinguish from other non-Langerhans cell histiocytoses, particularly xanthogranuloma (XG). Pathologists use S100 immunoreactivity, abundant plasma cells, and the presence of emperipolesis to distinguish RDD from XG. However, S100 expression has been reported in XG and, in practice, we have occasionally observed emperipolesis in cases that were otherwise clinically and pathologically consistent with XG. We present 10 cases of XG with emperipolesis and variable S100 immunoreactivity. Histologically, 7 cases were most in keeping with XG, and a histologic differential of XG versus RDD was raised in the remaining 3 cases. All 10 cases were clinically consistent with XG. Notably, none of these cases showed abundant plasma cells. Nine cases showed variable S100 immunostaining, ranging from focal/weak expression, to focal/strong, diffuse/moderate, and diffuse/strong expression. Histiocytes in all cases were CD68 positive and CD1a negative. We conclude that emperipolesis and S100 expression in a skin biopsy cannot reliably distinguish XG from cutaneous manifestations of RDD. Clinical correlations are essential, as are histologic clues to a diagnosis of classic XG that include an abundance of foamy mononuclear cells, Touton giant cells, and an absence of pale stained histiocytes, abundant plasma cells, fibrosis, or vascular proliferation. PMID- 29797337 TI - Re: Chokesuwattanaskul et al. Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: Meta-analysis. PMID- 29797338 TI - Urinary oxytocin in capuchin monkeys: Validation and the influence of social behavior. AB - In highly social species, like primates, oxytocin plays an important role in cooperation, and in the formation and maintenance of social relationships. Despite recent interest in the relationship between oxytocin and social behavior in nonhuman primates, relatively little is known about endogenous oxytocin in social New World Monkeys. In this paper, we investigate the relationship between oxytocin and affiliative behaviors in socially-housed captive capuchin monkeys (Sapajus [Cebus] apella) by first validating methods of analysis of urinary oxytocin in this species and, second, examining the effects of grooming and fur rubbing behavior on oxytocin concentrations and further affiliative behavior. In the validation, we found that intranasal exogenous oxytocin significantly increased urinary oxytocin 15-60 min post-administration. Oxytocin was also implicated in both grooming and fur-rubbing behaviors. We found that oxytocin concentrations increased after subjects engaged in grooming or fur-rubbing. In addition, we found that fur-rubbing influenced affiliative behaviors, both during and after a social fur-rubbing bout. While individuals spent more time in contact and proximity while fur-rubbing, immediately following the fur-rubbing event (15 30 min afterwards) all affiliative behaviors decreased. This supports previous research that oxytocin may, in fact, initially be related to increased social distance in this species. Yet, an increase in all affiliative behaviors 30-45 min after the onset of fur-rubbing suggests that fur-rubbing, like grooming, may ultimately function to strengthen social relationships. Overall, these results support a critical role for oxytocin in affiliative behaviors that maintain and strengthen social relationships in capuchin monkeys, and highlight the complexity of the interactions among oxytocin, affiliative behaviors, and social bonding. PMID- 29797340 TI - Differential insular cortex subregional vulnerability to alpha-synuclein pathology in Parkinson's disease and dementia with Lewy bodies. AB - AIM: The insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals alpha-synuclein pathology in advanced stages. The aim of this study is to assess the insular cortex cellular and subregional vulnerability to alpha-synuclein pathology in well-characterized PD and DLB subjects. METHODS: We analysed postmortem insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age matched controls. The load and distribution of alpha-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior insula and astroglia was assessed in all groups. RESULTS: A decreasing gradient of alpha synuclein pathology load from the anterior periallocortical agranular towards the intermediate dysgranular and posterior isocortical granular insular subregions was found. Few VENs revealed alpha-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the agranular and dysgranular subregions but did not reveal alpha synuclein inclusions or significant reduction in density in patient groups. CONCLUSIONS: Our study highlights the vulnerability of the anterior agranular insula to alpha-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, insular TH neurons were spared. Owing to the anterior insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB. PMID- 29797341 TI - Comparison of five methods for the estimation of methane production from vented in vitro systems. AB - BACKGROUND: There are several methods for estimating methane production (MP) from feedstuffs in vented in vitro systems. One method (A; 'gold standard') measures methane proportions in the incubation bottle's headspace (HS) and in the vented gas collected in gas bags. Four other methods (B, C, D and E) measure methane proportion in a single gas sample from the HS. Method B assumes the same methane proportion in the vented gas as in the HS, method C assumes constant methane to carbon dioxide ratio, method D has been developed based on empirical data, and method E assumes constant individual venting volumes. This study aimed to compare the MP predictions from these methods to that of the gold standard method under different incubation scenarios, to validate these methods based on their concordance with a gold-standard method. RESULTS: Methods C, D and E had greater concordance (0.85, 0.88 and 0.81), lower root-mean-square error (RMSE; 0.80, 0.72 and 0.85) and lower mean bias (0.20, 0.35, -0.35) with the gold standard than did method B (concordance 0.67, RMSE 1.49 and mean bias 1.26). Methods D and E were simpler to perform than method C, and method D was slightly more accurate than method E. CONCLUSION: Based on precision, accuracy and simplicity of implementation, it is recommended that, when method A cannot be used, methods D and E are preferred to estimate MP from vented in vitro systems. (c) 2018 Society of Chemical Industry. PMID- 29797339 TI - Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques. AB - Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in-group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT-and AVP-containing neurons project into the cortex. Here, we demonstrate the existence of OT- and AVP containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT-immunoreactive fibers were found in macaque cortex. AVP immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non-human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions. PMID- 29797343 TI - Epithelial sheath neuroma with extension to the subcutis. AB - Epithelial sheath neuroma (ESN) is a rare entity, histologically showing enlarged nerves in the superficial dermis surrounded by cytologically bland keratinocytes, classically presenting clinically as an erythematous papule or nodule on the back of middle-aged to elderly individuals. Clear-cut recommendations for treatment are not available, with many reports citing biopsy alone or simple excision as curative. We report a case of biopsy-proven ESN presenting as a significantly painful nodule in an elderly woman. Surgical excision was performed for symptom control and the residual ESN was found to extend deep into the subcutis. PMID- 29797342 TI - Integration of hepatitis B virus DNA in chronically infected patients assessed by Alu-PCR. AB - Hepatitis B virus (HBV) infection is the main risk factor for hepatocellular carcinoma (HCC) worldwide. Integration of HBV DNA into the human genome has been found in >80% of HBV-related HCC cases. Some studies have, however, found similar integration patterns in tumorous and nontumorous tissues. Thus, the role of integrations for the development of HCC as well as the rate of integration in different stages of infection remain unclear. The aim of this study was to investigate integrations in patients without HCC, representing different stages of chronic HBV (CHB) infection. Extracted DNA in liver biopsies from 74 patients (one with 2 available biopsies) with CHB infection was analyzed by Alu-PCR. Amplicons were further analyzed by Sanger sequencing. Integration was detected in 39 biopsies (52%) as an amplicon containing both human and HBV sequences by Alu PCR with one primer targeting a region in the HBV genome. Integrations were found in patients representing the different stages of CHB infection. A majority of the HBV sequences were located upstream or downstream of nucleotide position 1820, which previously has been identified as a common breakpoint in the HBV genome in integrated sequences. Approximately 60% of the HBV integrations were found in noncoding regions of the human genome. Integrations of HBV DNA into the human genome is an event frequently found in mild phases of chronic hepatitis. PMID- 29797345 TI - Therapeutic effect of urethral sphincter onabotulinumtoxinA injection for urethral sphincter hyperactivity. AB - PURPOSE: Urethral sphincter hyperactivity resulting in voiding dysfunction is frequently encountered. Medical treatment might not achieve a satisfactory result. OnabotlinumtoxinA urethral sphincter injection relaxes sphincter tonicity and possibly resumes efficient voiding. This study analyzed the treatment outcomes and predictor for successful onabotulinumtoxinA treatment on these patients. METHODS: Patients with voiding dysfunction due to urethral sphincter hyperactivity and treated with injections of 100 U onabotulinumtoxinA into the urethral sphincter were retrospectively reviewed. Treatment outcomes were assessed 1 month after injection using the Global Response Assessment and were analyzed by demographic and baseline video-urodynamic characteristics. RESULTS: Of the 95 patients included, satisfactory outcomes were reported in 58 (61.1%) patients. Treatment outcome was not related to age, gender, or voiding dysfunction subtype. Patients with satisfactory outcomes had a significantly smaller volume at first sensation of filling (P = 0.046), greater detrusor pressure (P = 0.027), higher maximum flow rate (P = 0.017), and smaller post-void residual (P = 0.006). In multivariate analysis, an open bladder neck during voiding was the only predictor for successful outcome (88% in satisfactory outcome, 12% in failure outcome, P < 0.001). Patients with non-neurogenic voiding dysfunction had a significantly longer therapeutic duration than those with neurogenic voiding dysfunction (9.55 +/- 4.18 vs 7.44 +/- 2.91 months, P = 0.033). Increased urinary incontinence was reported in 18 patients, including 6 with stress urinary incontinence and 12 with urgency urinary incontinence. CONCLUSION: Subjective improvement was reported in 61.1% of patients with voiding dysfunction due to urethral sphincter hyperactivity after onabotulinumtoxinA urethral sphincter injection. An open bladder neck during voiding at baseline predicts a successful outcome. PMID- 29797344 TI - Atypical presentation of Dowling-Degos disease with novel and recurrent mutations in POFUT1. PMID- 29797346 TI - Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation. AB - The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb-induced neurotoxicity. Heme oxygenase 1 (HO-1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well-known inducer of HO-1, to investigate the possible role of HO-1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate-induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH-SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO-1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO-1 contributed to the protection. Finally, the HO-1-derived production of carbon monoxide, but not of bilirubin or Fe2+ , mediated the protective effects of HO-1 activation induced by hemin treatment against Pb-induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO-1/carbon monoxide activation. PMID- 29797348 TI - Dendritic cells and routing cargo into exosomes. AB - Extracellular vesicles, released from cells, are important for intercellular communication. They are heterogeneous but fall into two broad categories based on origin and function: microvesicles formed by outward budding from the plasma membrane; and exosomes that originate as intraluminal vesicles in multivesicular endosomes that fuse with the plasma membrane to release them. Extracellular vesicles generally and exosomes in particular have powerful effects on specific immune responses, and recent advances highlight their potential therapeutic uses. Dendritic cells (DC) that have internalized antigen release exosomes that express MHC class II molecules loaded with antigenic peptides, co-stimulatory molecules and intact antigen. Depending on the setting, these stimulate CD4 T-cell proliferation either directly or only in the context of accessory antigen naive DC. Here, we discuss the reasons for this; and review current knowledge about the loading of antigen, class II and other cargo into exosomes released by DC and other professional antigen-presenting cells in the context of advances in exosome biology more generally. PMID- 29797347 TI - WITHDRAWN: Resorbable versus titanium plates for facial fractures. AB - BACKGROUND: Rigid internal fixation of the jaw bones is a routine procedure for the management of facial fractures. Titanium plates and screws are routinely used for this purpose. The limitations of this system has led to the development of plates manufactured from bioresorbable materials which, in some cases, omits the necessity for the second surgery. However, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. OBJECTIVES: To compare the effectiveness of bioresorbable fixation systems with titanium systems for the management of facial fractures. SEARCH METHODS: We searched the following databases: The Cochrane Oral Health Group's Trials Register (to 20th August 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to 20th August 2008), EMBASE (from 1980 to 20th August 2008), http://www.clinicaltrials.gov/ and http://www.controlled-trials.com (to 20th August 2008). SELECTION CRITERIA: Randomised controlled trials comparing resorbable versus titanium fixation systems used for facial fractures. DATA COLLECTION AND ANALYSIS: Retrieved studies were independently screened by two review authors. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. MAIN RESULTS: The search strategy retrieved 53 potentially eligible studies. None of the retrieved studies met our inclusion criteria and all were excluded from this review. One study is awaiting classification as we failed to obtain the full text copy. Three ongoing trials were retrieved, two of which were stopped before recruiting the planned number of participants. In one study, the excess complications in the resorbable arm was declared as the reason for stopping the trial. AUTHORS' CONCLUSIONS: This review illustrates that there are no published randomised controlled clinical trials relevant to this review question. There is currently insufficient evidence for the effectiveness of resorbable fixation systems compared with conventional titanium systems for facial fractures. The findings of this review, based on the results of the aborted trials, do not suggest that resorbable plates are as effective as titanium plates. In future, the results of ongoing clinical trials may provide high level reliable evidence for assisting clinicians and patients for decision making. Trialists should design their studies accurately and comprehensively to meet the aims and objectives defined for the study. PMID- 29797349 TI - White-coat hypertension from a paediatric perspective. AB - AIM: This mini review explored the prevalence of white-coat hypertension (WCH), which is very common in children. It results in elevated office blood pressure (BP) but normal ambulatory BP monitoring (ABPM) readings. METHODS: WCH can only be identified by analysing and comparing office BP readings and ABPM, which periodically records BP every 20-30 minutes over 24-hour period. This study provides initially the background for WCH in adults, together with a comprehensive overview of the most relevant paediatric data on WCH. RESULTS: Accurate measurements of BP are very important for the diagnosis and management of hypertension. It is important to acknowledge the clinical relevance of WCH and follow up children who display this BP phenotype by carrying out ABPM, so that clinicians can build up an accurate picture of their BP. It is also important to identify children who have BP issues and are overweight or obese, so that treatment of this modifiable cardiovascular risk factor can be initiated. CONCLUSION: Using ABPM provides paediatricians with a more precise evaluation of a child's BP readings than office BP readings. It is the gold standard for diagnosing WCH. PMID- 29797350 TI - Resilience and social support as protective factors against abuse of patients with dementia: A study on family caregivers. AB - OBJECTIVE: Scientific literature has identified different vulnerability factors associated to abuse in people with dementia (PWD), but little is known about the psychosocial protective variables against abuse. The main objective of this study is to investigate a set of caregiver and patient factors linked to abuse-related behavior of PWD. METHODS: A total of 326 primary and family caregivers, residents of the Castilla and Leon community (Spain), were evaluated. All participants filled out a standardized protocol, which assessed the sociodemographic characteristics, patient and care-related variables, as well as the perceived burden, resilience, and social support. Abuse-related behavior was evaluated using the Caregiver Abuse Screen. RESULTS: Results show that the severity of cognitive impairment and behavior disorders of PWD, a greater number of caregiving hours, a worse previous relationship with the caregiver, and perceived burden are positively related with abuse. However, resilience and social support showed a negative relationship with Caregiver Abuse Screen scores, suggesting a protective effect on abuse, even after controlling the effect of a number of covariates. Indeed, resilience was the only variable that remained significant after including the effect of burden. CONCLUSIONS: This paper states the role of burden in abuse of PWD, while resilience and social support are abuse protective factors. These variables should be considered in future guidelines for the prevention of abuse against PWD. PMID- 29797351 TI - Decreased noradrenaline transporter density in the motor cortex of Parkinson's disease patients. AB - Reduced noradrenaline levels have been reported to occur in the motor cortices of PD patients postmortem. Imaging techniques have recently become available to specifically study noradrenergic terminal function in vivo using PET. The objective of this study was to evaluate cortical 11 C-MeNER binding in PD patients. Thirty PD patients and 12 healthy control subjects comparable in age, sex, and cognitive performance underwent PET imaging with 11 C-MeNER, a specific ligand of the noradrenaline transporter. Cortical noradrenaline transporter binding was compared at a voxel level using Statistical Parametric Mapping, whereas cortical thickness was assessed using FreeSurfer software with MRI. PD patients showed reduced 11 C-MeNER binding in the primary motor cortex unrelated to cortical thickness; other cortical regions did not differ between groups. In a subgroup analysis, patients with higher Hoehn & Yahr stage exhibited more pronounced 11 C-MeNER binding reductions. Loss of cortical noradrenergic projections to the primary motor cortex occurs in PD associated with disease stage. (c) 2018 International Parkinson and Movement Disorder Society. PMID- 29797352 TI - Cardiac repolarization and depolarization in people with Type 1 diabetes with normal ejection fraction and without known heart disease: a case-control study. AB - AIMS: To investigate depolarization and repolarization durations in people with Type 1 diabetes, including the relationship to age. METHODS: 855 persons with Type 1 diabetes without known heart disease were included and matched with 1710 participants from a general population study. Clinical examinations, questionnaires and biochemistry were assessed. A 10-second 12-lead ECG was performed and analysed digitally. RESULTS: QTc was longer in people with Type 1 diabetes compared to controls (414+/-16 vs. 411+/-19 ms, P <0.001), and particularly so in young people with Type 1 diabetes. The fully adjusted increase was 13.8 ms (95% confidence interval (CI): 8.6-19.0 ms, P <0.001) at age 20 years and 3.4 ms (CI: 1.5-5.3 ms, P<0.001) at age 40 years. The rate-corrected QRSc was increased in people with Type 1 diabetes (97+/-11 vs. 95+/-11 ms, P <0.001) and was age-independent (P =0.5). JTc was increased in the young people with Type 1 diabetes (10.7 ms (CI: 5.4-16.0 ms, P <0.001) at age 20 years), but not in older people with Type 1 diabetes (interaction age-diabetes, P <0.01). CONCLUSIONS: For people with Type 1 diabetes, cardiac depolarization is increased at all ages, whereas repolarization is increased only relatively in young people with Type 1 diabetes. Hence, young people with Type 1 diabetes may be more prone to ventricular arrhythmias. The findings contribute to the understanding of sudden cardiac death in young people with Type 1 diabetes. PMID- 29797353 TI - High accuracy of proximity extension assay technology for the quantification of plasma brain natriuretic peptide. AB - BACKGROUND: Novel multiplex assays allow the simultaneous identification of a large number of plasma proteins. While these new technologies have been shown to be highly sensitive and accurate for the identification of plasma proteins, the use of this technology to quantify those proteins has not been properly investigated. In this pilot study, we tested the accuracy of the proximity extension assay (PEA) for the quantification of the cardiac biomarker brain natriuretic peptide (BNP) compared to a standard clinically approved method. METHODS: Concentrations of BNP were assessed in 120 plasma samples from 30 patients with PEA and compared to chemiluminescent microparticle immunoassay (CMIA). Venous blood samples were collected from in tubes containing ethylenediaminetetraacetic acid, centrifuged within 6 hours at 3,500 rpm for 15 minutes at 4 degrees C, frozen and stored at -80 degrees C until analyzed. Correlation between the CMIA and PEA techniques was tested using the Spearman's rank correlation coefficient (rho) and the agreement was described with a Bland Altman plot. RESULTS: Brain natriuretic peptide values obtained by CMIA and PEA were highly correlated (Spearman's rho = 0.865, P < .0001). In two patients, PEA consistently overestimated resp. underestimated BNP values compared to CMIA. After removal of those two patients, a very high correlation between the two techniques was shown (rho = 0.966, P < .0001). A high agreement between the two techniques over the whole range of tested concentrations was shown. CONCLUSION: This pilot study showed for the first time an excellent correlation between a clinically approved method and the PEA-based approach for quantification of circulating plasma BNP. PMID- 29797354 TI - Sperm nuclear protamines: A checkpoint to control sperm chromatin quality. AB - Protamines are nuclear proteins which are specifically expressed in haploid male germ cells. Their replacement of histones and binding to DNA is followed by chromatin hypercondensation that protects DNA from negative influences by environmental factors. Mammalian sperm contain two types of protamines: PRM1 and PRM2. While the proportion of the two protamines is highly variable between different species, abnormal ratios within a species are known to be associated with male subfertility. Therefore, it is more than likely that correct protamine expression represents a kind of chromatin checkpoint during sperm development rendering protamines as suitable biomarkers for the estimation of sperm quality. This review presents an overview of our current knowledge on protamines comparing gene and protein structures between different mammalian species with particular consideration given to man, mouse and stallion. At last, recent insights into the possible role of inherited sperm histones for early embryo development are provided. PMID- 29797355 TI - Selective forgetting of self-threatening statements: Mnemic neglect for dementia information in people with mild dementia. AB - OBJECTIVE: We tested whether people with dementia manifest selective forgetting for self-threatening information, the mnemic neglect effect (MNE). This selective forgetting is observed among healthy adults in the recall, but not the recognition, of self-threatening feedback. METHODS: Sixty-four statements about dementia were rated for their level of negativity by 280 staff and students at University of the West of England. The 12 statements rated as most negative and the 12 statements rated as least negative were then read to 62 people with dementia. Participants were randomized to 1 of 2 conditions with the statements referring either to self or to another person. High-negativity and self-referent statements had strong threat potential. Participants recalled the statements and then completed a recognition task, which consisted of the 24 previously read statements and 24 new statements. RESULTS: Participants manifested the MNE: They recalled fewer high-negativity (compared with low-negativity) statements, but only when these referred to the self rather than another person. This pattern occurred independently of levels of depression or anxiety. Participants also made more self-protective intrusion errors when the statements referred to the self than another person. Participants did not differ in their recognition of statements. CONCLUSION: The MNE occurs among people with dementia. The selective forgetting of highly negative, self-referent statements serves to protect the self against the threat that dementia represents. Given the similarities between the MNE and the clinical phenomenon of repression, the findings may mark psychological processes that are implicated in the acceptance (or lack thereof) of a dementia diagnosis. PMID- 29797356 TI - Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction. AB - AIMS: To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. METHODS: Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. RESULTS: ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. CONCLUSIONS: Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle. PMID- 29797358 TI - Mechanotargeting: Mechanics-Dependent Cellular Uptake of Nanoparticles. AB - Targeted delivery of nanoparticle (NP)-based diagnostic and therapeutic agents to malignant cells and tissues has exclusively relied on chemotargeting, wherein NPs are surface-coated with ligands that specifically bind to overexpressed receptors on malignant cells. Here, it is demonstrated that cellular uptake of NPs can also be biased to malignant cells based on the differential mechanical states of cells, enabling mechanotargeting. Owing to mechanotransduction, cell lines (HeLa and HCT-8) cultured on hydrogels of various stiffness are directed into different stress states, measured by cellular force microscopies. In vitro NP delivery reveals that increases in cell stress suppress cellular uptake, counteracting the enhanced uptake that occurs with increases in exposed surface area of spread cells. Upon prolonged culture on stiff hydrogels, cohesive HCT-8 cell colonies undergo metastatic phenotypic change and disperse into individual malignant cells. The metastatic cells are of extremely low stress state and adopt an unspread, 3D morphology, resulting in several-fold higher uptake than the nonmetastatic counterparts. This study opens a new paradigm of harnessing mechanics for the design of future strategies in nanomedicine. PMID- 29797357 TI - The challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy. AB - BACKGROUND: Seborrheic keratosis (SK) is one of the most common skin tumors seen by dermatologists. It should be differentiated with many diseases, especially skin tumors. Reflectance confocal microscopy (RCM) has been applied for evaluation of SK. There are a few studies that describe the RCM of SK. The aim of the study was to find the challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy. METHODS: A total of 390 patients with a clinical suspicious diagnosis of seborrheic keratosis were enrolled in this study, and lesions from each patient were imaged with RCM. Thirty-seven of these patients performed a biopsy in order to be given a histological diagnosis. We retrospectively analyzed the outcomes of RCM diagnosis and histological diagnosis, and then found the RCM characteristics of biopsy-proven lesions. RESULTS: According to RCM images, 258 of 390 (66.2%) patients were diagnosed with SK, 97 of 390 (24.9%) patients could not be diagnosed by the dermatologist according to RCM. Of all 37 biopsied lesions, 23 were SK, 6 were actinic keratosis, 2 were basal cell carcinoma, and 2 were squamous cell carcinoma. CONCLUSION: It is challenge to diagnose seborrheic keratosis by reflectance confocal microscopy. It may due to the variable clinical and RCM appearances of SK, and limited depth of RCM. PMID- 29797359 TI - Reverse Saturable Absorption Induced by Phonon-Assisted Anti-Stokes Processes. AB - In materials showing reverse saturable absorption (RSA), optical transmittance decreases at intense laser irradiation. One approach to application of these materials is to protect the sensors or human eyes from laser damage. To date, research has mainly concentrated on thin films and suspensions of graphite and its nanostructure (including nanotubes, graphene, and graphene oxides), which are mainly used as an optical limiter for nanosecond laser pulses. Moreover, thin individual pieces of semiconductor usually exhibit increased transmittance due to saturable absorption when the laser energy (Elaser ) is higher than the band gap (EB ). Here, it is shown that indirect gap semiconductor WSe2 exhibits high RSA on exposure to a femtosecond laser under Elaser > EB near band gap excitation, which is attributed to the longitudinal optical phonon-assisted anti-Stokes transition by the annihilation of phonons and the absorption of photons. An optical limiting threshold (~21.6 mJ cm-2 ) lower than those reported for other optical-limiting materials currently for femtosecond laser at 800 nm is observed. PMID- 29797360 TI - Strategies to assist uptake of pelvic floor muscle training for people with urinary incontinence: A clinician viewpoint. AB - AIMS: The experiences and information needs of clinicians who use pelvic floor muscle training to manage urinary incontinence were explored. METHODS: Qualitative methods were used to conduct thematic analysis of data collected from clinician focus groups and interviews. Participants were registered physiotherapists and continence nurses in Melbourne, Australia. Recruitment was through a combination of purposive and "snowball" sampling and continued until data adequacy was reached. RESULTS: Twenty-eight physiotherapists and one continence nurse participated in seven focus groups and one interview. The main finding communicated by the participants was that pelvic floor muscle training requires comprehensive descriptions of program details in order for clinicians to implement evidence-based interventions. The following themes were identified: (1) pelvic floor muscle training tailored to the needs of each individual is essential; (2) training-specific cues and verbal prompts assist patients to learn and engage with exercises; and (3) clinicians can benefit from research summaries and reports that provide explicit and comprehensive descriptions and decision rules about intervention content and progression. The data indicated that some clinicians can have difficulty interpreting and applying research findings because it is not always well reported. CONCLUSIONS: Clinicians who use pelvic floor muscle training to treat urinary incontinence advised can benefit from accessing explicit details of interventions tested in research and reported as effective. They viewed tailoring therapy to individual goals and the use of verbal prompts and visualization cues as important engagement strategies for effective exercise performance. Explicit reporting could be facilitated by using an exercise guideline template, such as the Consensus on Exercise Reporting Template (CERT). PMID- 29797361 TI - Travelling the circle together, solo: An individual protocol for the Circle of Security intensive intervention. AB - Circle of Security (COS) is an approach to help parents better understand the attachment needs of their children. The COS model, which began as an intensive, individualized intervention delivered in the context of a group, has been implemented in a variety of formats, including a DVD-based format (Circle of Security Parenting [COS-P]). This article presents a return to the original intensive intervention, adapted to be delivered in an individual therapy context and incorporating clips from COS-P. This approach emphasizes the importance of retaining video review within this intervention, showing the client directly interacting with his or her own child. The application of this hybrid format is demonstrated through the case of a mother and 5-year-old child presenting with difficulty negotiating separations. PMID- 29797362 TI - Cholinergic modulation of striatal microcircuits. AB - The purpose of this review is to bridge the gap between earlier literature on striatal cholinergic interneurons and mechanisms of microcircuit interaction demonstrated with the use of newly available tools. It is well known that the main source of the high level of acetylcholine in the striatum, compared to other brain regions, is the cholinergic interneurons. These interneurons provide an extensive local innervation that suggests they may be a key modulator of striatal microcircuits. Supporting this idea requires the consideration of functional properties of these interneurons, their influence on medium spiny neurons, other interneurons, and interactions with other synaptic regulators. Here, we underline the effects of intrastriatal and extrastriatal afferents onto cholinergic interneurons and discuss the activation of pre- and postsynaptic muscarinic and nicotinic receptors that participate in the modulation of intrastriatal neuronal interactions. We further address recent findings about corelease of other transmitters in cholinergic interneurons and actions of these interneurons in striosome and matrix compartments. In addition, we summarize recent evidence on acetylcholine-mediated striatal synaptic plasticity and propose roles for cholinergic interneurons in normal striatal physiology. A short examination of their role in neurological disorders such as Parkinson's, Huntington's, and Tourette's pathologies and dystonia is also included. PMID- 29797363 TI - A novel tomato F-box protein, SlEBF3, is involved in tuning ethylene signaling during plant development and climacteric fruit ripening. AB - Ethylene is instrumental to climacteric fruit ripening and EIN3 BINDING F-BOX (EBF) proteins have been assigned a central role in mediating ethylene responses by regulating EIN3/EIL degradation in Arabidopsis. However, the role and mode of action of tomato EBFs in ethylene-dependent processes like fruit ripening remains unclear. Two novel EBF genes, SlEBF3 and SlEBF4, were identified in the tomato genome, and SlEBF3 displayed a ripening-associated expression pattern suggesting its potential involvement in controlling ethylene response during fruit ripening. SlEBF3 downregulated tomato lines failed to show obvious ripening-related phenotypes likely due to functional redundancy among SlEBF family members. By contrast, SlEBF3 overexpression lines exhibited pleiotropic ethylene-related alterations, including inhibition of fruit ripening, attenuated triple-response and delayed petal abscission. Yeast-two-hybrid system and bimolecular fluorescence complementation approaches indicated that SlEBF3 interacts with all known tomato SlEIL proteins and, consistently, total SlEIL protein levels were decreased in SlEBF3 overexpression fruits, supporting the idea that the reduced ethylene sensitivity and defects in fruit ripening are due to the SlEBF3-mediated degradation of EIL proteins. Moreover, SlEBF3 expression is regulated by EIL1 via a feedback loop, which supposes its role in tuning ethylene signaling and responses. Overall, the study reveals the role of a novel EBF tomato gene in climacteric ripening, thus providing a new target for modulating fleshy fruit ripening. PMID- 29797364 TI - Abnormal Synergetic Effect of Organic and Halide Ions on the Stability and Optoelectronic Properties of a Mixed Perovskite via In Situ Characterizations. AB - The mixed cation lead mixed halide perovskite (MLMP) Csx FA1-x PbIy Br3-y is one of the most promising candidates for both single-junction and tandem solar cells due to its high efficiency and remarkable stability. However, the composition effect on thermal stability and photovoltaic performances has not yet been comprehensively investigated. Therefore, the interplay between composition, crystal structure, morphology, and optoelectronic properties under heat stress, is systematically elucidated here through a series of in situ characterizations. It is revealed for the first time that the FA+ and Br- release synchronously at first even under mild annealing. This leads to a serious FA- and Br-deficiency issue, with only 88.3% of Br and 90.2% of FA retained after annealing at 100 degrees C, which significantly magnifies the hysteresis, phase segregation, and instability issues. Finally, a trace amount of FA+ and Br- is introduced onto the post-annealed MLMP surface to compensate for the deficiency through vacancy filling. The degradation lifetime to 80% of the initial efficiency (t80 ) is improved from 504 to 1056 h and the hysteresis issue is also well resolved. This work highlights the importance of the synergetic composition effect of the organic cation and halide anion on stability and efficiency optimization for long term applications. PMID- 29797365 TI - Endobronchial ultrasound guided transbronchial needle aspirate from subcarinal lymph node: Mesothelial lesion, a diagnostic dilemma. PMID- 29797366 TI - Nucleotide-binding resistance gene signatures in sugar beet, insights from a new reference genome. AB - Nucleotide-binding (NB-ARC), leucine-rich-repeat genes (NLRs) account for 60.8% of resistance (R) genes molecularly characterized from plants. NLRs exist as large gene families prone to tandem duplication and transposition, with high sequence diversity among crops and their wild relatives. This diversity can be a source of new disease resistance, but difficulty in distinguishing specific sequences from homologous gene family members hinders characterization of resistance for improving crop varieties. Current genome sequencing and assembly technologies, especially those using long-read sequencing, are improving resolution of repeat-rich genomic regions and clarifying locations of duplicated genes, such as NLRs. Using the conserved NB-ARC domain as a model, 231 tentative NB-ARC loci were identified in a highly contiguous genome assembly of sugar beet, revealing diverged and truncated NB-ARC signatures as well as full-length sequences. The NB-ARC-associated proteins contained NLR resistance gene domains, including TIR, CC and LRR, as well as other integrated domains. Phylogenetic relationships of partial and complete domains were determined, and patterns of physical clustering in the genome were evaluated. Comparison of sugar beet NB-ARC domains to validated R-genes from monocots and eudicots suggested extensive Beta vulgaris-specific subfamily expansions. The NLR landscape in the rhizomania resistance conferring Rz region of Chromosome 3 was characterized, identifying 26 NLR-like sequences spanning 20 MB. This work presents the first detailed view of NLR family composition in a member of the Caryophyllales, builds a foundation for additional disease resistance work in B. vulgaris, and demonstrates an additional nucleic-acid-based method for NLR prediction in non-model plant species. PMID- 29797367 TI - Copy number variations of MTHFSD gene across pig breeds and its association with litter size traits in Chinese indigenous Xiang pig. AB - Copy number variation (CNV) is a major proportion of genetic variation, which changes the gene structure and dosage and affects gene expression and function. To validate the presence and the function of CNV in pig, we used real-time quantitative polymerase chain reaction (qPCR) method to validate a 496 kb CNV region comprising MTHFSD gene on chromosome 6 of Xiang pig detected by single nucleotide polymorphism (SNP) array. Then we investigated the distribution of the MTHFSD CNV in a total of 545 pigs in four breeds. About 46.2% and 32.7% individuals in the four pig breeds were detected to be types of loss and gain of MTHFSD locus. The relative copy numbers of MTHFSD gene showed the largest variation range (0-55 copies) in the Xiang pig population. The copy numbers of MTHFSD gene presented the positive correlations with the transcript level of MTHFSD gene in adult ovaries. Statistical analysis indicated that CNVs of MTHFSD gene was significantly changed the litter size traits of Xiang pigs, and the individuals with CNV gain showed more litter size than the CNV loss pigs. We have reasons to believe that the MTHFSD as RNA-binding protein play an important role in pig reproduction as a result of regulating MTHFS mRNA metabolism. PMID- 29797368 TI - SIG1459: A novel phytyl-cysteine derived TLR2 modulator with in vitro and clinical anti-acne activity. AB - Cutibacterium (formerly Propionibacterium acnes) is a major contributor to the pathogenesis of acne. C. acnes initiates an innate immune response in keratinocytes via recognition and activation of toll-like receptor-2 (TLR2), a key step in comedogenesis. Tetramethyl-hexadecenyl-cysteine-formylprolinate (SIG1459), a novel anti-acne isoprenylcysteine (IPC) small molecule, is shown in this study to have direct antibacterial activity and inhibit TLR2 inflammatory signalling. In vitro antibacterial activity of SIG1459 against C. acnes was established demonstrating minimal inhibitory concentration (MIC = 8.5 MUmol?L), minimal bactericidal concentration (MBC = 16.1 MUmol?L) and minimal biofilm eradication concentration (MBEC = 12.5 MUmol?L). To assess SIG1459's anti inflammatory activity, human keratinocytes were exposed to C. acnes and different TLR2 ligands (peptidoglycan, FSL-1, Pam3CSK4) that induce pro-inflammatory cytokine IL-8 and IL-1alpha production. Results demonstrate SIG1459 inhibits TLR2 induced IL-8 release from TLR2/TLR2 (IC50 = 0.086 MUmol?L), TLR2/6 (IC50 = 0.209 MUmol?L) and IL-1alpha from TLR2/TLR2 (IC50 = 0.050 MUmol?L). To assess the safety and in vivo anti-acne activity of SIG1459, a vehicle controlled clinical study was conducted applying 1% SIG1459 topically (n = 35 subjects) in a head-to-head comparison against 3% BPO (n = 15 subjects). Utilizing the Investigator Global Assessment scale for acne as primary endpoint, results demonstrate 1% SIG1459 significantly outperformed 3% BPO over 8 weeks, resulting in 79% improvement as compared to 56% for BPO. Additionally, 1% SIG1459 was well tolerated. Thus, SIG1459 and phytyl IPC compounds represent a novel anti-acne technology that provides a safe dual modulating benefit by killing C. acnes and reducing the inflammation it triggers via TLR2 signalling. PMID- 29797369 TI - Instant Detection of Hydrogen Cyanide Gas and Cyanide Salts in Solid Matrices and Water by using CuII and NiII Complexes of Intramolecularly Hydrogen Bonded Zwitterions. AB - A series of intramolecularly hydrogen-bonded zwitterionic compartmental ligands HL1-HL4, containing a pendent diamine arm that is monoprotonated and an aldehyde functionality at two different ortho-positions of a 4-halophenoxide, is reported herein. Single-crystal X-ray diffraction (SXRD) provides persuasive evidence for the identification of this class of proton-transferred zwitterions at room temperature. The solid-state photoluminescent nature of these zwitterions remains intact in aqueous and organic solutions. Grinding of HL1 and HL2 with Cu2+ /Ni2+ salts develop turn-on probes 1-4. Compounds 1 and 4 are dinuclear CuII and NiII species, respectively. Compound 2 is a tetranuclear CuII complex. Interestingly, compound 3 is a mononuclear NiII species in which both nitrogen atoms in the pendant diamine arm are protonated and, therefore, not coordinated to the NiII center. All these probes (1-4) display an instant response to the poison gas hydrogen cyanide (HCN) and cyanide salts present in both solid matrices and aqueous (100 % water) solution. Selective and rapid sensing of HCN gas and cyanide salts in solid/soil/water phases, without any interference, by the mechanosynthesized complexes 1-4 can be perceived easily by the naked eye under a hand-held UV lamp. PMID- 29797370 TI - Differential outcome subgroups in children with autism spectrum disorder attending early intervention. AB - BACKGROUND: The finding of positive outcomes at the group level for children with autism spectrum disorder (ASD) who complete comprehensive early intervention programmes often masks considerable individual variability. We therefore aimed to identify subgroups of children based on their response to intervention and to compare outcome variables between groups at two points in time. METHOD: We used model-based cluster analysis to explore response to intervention using a longitudinal design for 210 children with ASD who had completed an early intervention programme. Children were assessed on entry at time 1 and again at time 2, which was after 12 months or when they exited the programme (whichever came first) using measures of ASD symptoms (Social Communication Questionnaire), cognition (Mullen Scales of Early Learning) and adaptive behaviour (Vineland Adaptive Behaviour Scales-II). RESULTS: A two-cluster solution was identified, including a high change group who improved consistently more than the low change group across measures, and showed significantly fewer autism symptoms, higher non verbal and verbal cognition and adaptive behaviour composite scores at time 1. CONCLUSIONS: The findings indicated that children's response to early intervention is not uniform but instead included subgroups characterised by patterns of high and low change. Further research is needed to identify clinically relevant mediators of differential response group membership. PMID- 29797371 TI - Neuropathic pain is not adequately treated in the older general population: Results from the KORA F4 survey. AB - PURPOSE: We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. METHODS: The study included subjects aged 61 to 82 years from the KORA F4 survey (2006 2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. RESULTS: From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of >=4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. CONCLUSIONS: In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs. PMID- 29797372 TI - Addressing population levels of physical activity requires investment beyond the health sector. PMID- 29797373 TI - A Rapid and Robust Diagnostic for Liver Fibrosis Using a Multichannel Polymer Sensor Array. AB - Liver disease is the fifth most common cause of premature death in the Western world, with the irreversible damage caused by fibrosis, and ultimately cirrhosis, a primary driver of mortality. Early detection of fibrosis would facilitate treatment of the underlying liver disease to limit progression. Unfortunately, most cases of liver disease are diagnosed late, with current strategies reliant on invasive biopsy or fragile lab-based antibody technologies. A robust, fully synthetic fluorescent-polymer sensor array is reported, which, rapidly (in 45 minutes), detects liver fibrosis from low-volume serum samples with clinically relevant specificity and accuracy, using an easily readable diagnostic output. The simplicity, rapidity, and robustness of this method make it a promising platform for point-of-care diagnostics for detecting and monitoring liver disease. PMID- 29797374 TI - Clinical evaluation of Roche COBAS(r) AmpliPrep/COBAS(r) TaqMan(r) CMV test using nonplasma samples. AB - Cytomegalovirus (CMV) infection is a leading cause of loss of hearing, vision, and mental retardation in congenitally infected children. It is also associated with complications of organ transplant and opportunistic HIV coinfection. The Roche COBAS(r) AmpliPrep/COBAS(r) TaqMan(r) CMV test is an FDA-approved test that measures CMV DNA viral load in plasma for the diagnosis and management of patients at risk of CMV-associated diseases. Besides plasma, CMV is often found in bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), and urine. Thus, monitoring of CMV for critical care of patients in these nonplasma samples becomes necessary. The objective of this study was to conduct an analytic and clinical feasibility study of the Roche CMV test in BAL, CSF, and urine. The lower limit of detection, analytic measurement range, assay sensitivity, specificity, and precision were determined. Results of this study showed that the lower limit of detections were 50, 100, and 300 IU/mL for BAL, CSF, or urine, respectively. The analytic measurement ranges were from log10 2.48 to log10 5.48. The assay specificity was 94.4% for BAL and 100% for CSF and urine. The assay precision was all within the acceptable range. The performance of Roche test was further compared with 2 comparators including the RealTime CMV assay (Abbott Molecular) and a CMV Quantitative Polymerase Chain Reaction test (Vela Diagnostics). There was a general positive correlation between the Roche method and the Abbott or the Vela method. Overall, this study suggests that the Roche CMV test is suitable for the quantification of CMV viral load DNA in the described nonplasma samples. PMID- 29797375 TI - Medical nutrition treatment of women with gestational diabetes mellitus by a telemedicine system based on smartphones. AB - AIM: To explore whether WeChat platform-based treatment of women with gestational diabetes mellitus (GDM) reduces the risk of perinatal complications and explore factors affecting gestational age at delivery. METHODS: Pregnant women with GDM (n = 107) and normal glucose tolerance (n =50, group C) according to oral glucose tolerance test (OGTT) results during gestational weeks 24-28 were included. Women with GDM were divided into groups A (n =57) and B (n =50) according to informed consent. According to GDM treatment norms, group B was given routine outpatient treatment and health education guidance. In addition to the interventions in group B, group A was given access to both a smartphone-based telemedicine system and articles providing continuous health education. The PBG level in groups A and B was compared, as were differences in maternal and fetal outcomes. Data were analyzed by t-test, analysis of variance (anova), chi-square test and multiple linear regression, with P < 0.05 considered significant. RESULTS: Fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG) were significantly lower and premature delivery was significantly less likely in group A than in group B (all P < 0.05). Compared with group B, caesarean section was more likely in group A (P < 0.05). Pregnancy-induced hypertension had a higher incidence in group B than in group C (P < 0.05). Gestational age at delivery was associated with OGTT2h, premature fetal membrane rupture and self-monitoring of blood glucose. CONCLUSION: GDM treatment based on the WeChat platform effectively reduces FBG and 2-h PBG and may improve pregnancy outcomes. However, 1-h PBG was not affected by treatment. Obstetricians should consider the OGTT2h value to increase gestational age at delivery. PMID- 29797376 TI - Linaclotide inhibits colonic and urinary bladder hypersensitivity in adult female rats following unpredictable neonatal stress. AB - BACKGROUND: Irritable bowel syndrome (IBS) and bladder pain syndrome (BPS) are female-predominant, chronic functional pain disorders that are associated with early life stress (ELS) and therapeutic options for such patients remain limited. Linaclotide, a guanylate cyclase-C (GC-C) agonist, relieves abdominal pain and bowel symptoms in adult patients suffering from IBS with constipation. Here, we test the hypothesis that linaclotide will reverse colon and bladder hyperalgesia in a female-specific rodent model of adverse early life experience. METHODS: Neonatal rats were exposed to an odor-attachment learning paradigm of early life stress (ELS). In adulthood, the effect of linaclotide (3 MUg kg-1 d-1 , p.o.) on colonic and bladder sensitivity was assessed via quantification of the visceromotor response to colorectal distension and the frequency of withdrawal responses to the application of von Frey hairs to the suprapubic region. In another cohort of rats, the effect of linaclotide on ELS-induced colonic and bladder permeability was investigated via measurements of transepithelial electrical resistance (TEER). KEY RESULTS: Rats exposed to unpredictable ELS exhibited colonic and bladder hypersensitivity that was significantly reduced by linaclotide compared to vehicle-treated controls. Colonic and bladder tissue isolated from adult rats exposed to unpredictable ELS exhibited a decrease in colonic and bladder TEER that was reversed by linaclotide. CONCLUSIONS AND INFERENCES: Our results demonstrate that neonatal rats exposed to unpredictable ELS develop increased sensitivity and permeability of the colon and bladder in adulthood through a mechanism involving activation of peripheral GC-C signaling. PMID- 29797378 TI - Compassion satisfaction, burnout and secondary traumatic stress among termination of pregnancy providers in two South African provinces. AB - Focusing on compassion satisfaction, burnout and secondary traumatic stress (STS) among termination of pregnancy (TOP) providers, a cross - sectional study was conducted among these providers in Gauteng and North West provinces of South Africa during 2014 and 2015. During 2014 and 2015, a cross-sectional study was conducted among TOP service providers in Gauteng and North West provinces. Consented providers completed a self-administered professional quality of life (PRoQOL) questionnaire, sociodemographic information and possible reasons for working as TOP providers. STATA 13 was used for data analysis. We recruited 105 TOP providers, obtaining 98% response rate. Participants mean age was 43.4 (standard deviation [SD] = 8.7), majority were nurses (70.9%), female (82%), married (47.6%) and 63% were working in hospitals. The overall mean score for compassion satisfaction was high at 42 (SD 5.5). Predictors of compassion satisfaction were finding work stimulating, belief in making a difference, enjoying relationships with other nurses and years of TOP service (P < 0.05). Province and gender were significant, with significant interaction. Burnout mean scores were average at 33 (SD = 4.0), with belief in helping women to make informed choices a marginally significant predictor of burnout. The overall STS mean score was average with a mean of 23 (SD = 6.8). Significant predictors of STS scores were finding work stimulating, belief in women's rights, belief in allowing informed choices, age and gender. Health policy makers and managers should endeavor to provide employee assistance programs that enhance compassion satisfaction and reduce burnout and STS among TOP providers. PMID- 29797380 TI - Ultrathin Amorphous Iron-Nickel Boride Nanosheets for Highly Efficient Electrocatalytic Oxygen Production. AB - A cost-effective and efficient electrocatalyst for the oxygen evolution reaction during the electrolysis of water is highly desired. In an effort to develop an economical material for replacing precious-metal-based catalysts, a novel and self-standing amorphous ultrathin nanosheet (NS) of bimetallic iron-nickel boride (Fe-Ni-B NSs) on Ni foam is presented, which displays a better oxygen-evolving activity compared to the precious-metal catalyst RuO2 . In 1.0 m KOH electrolyte solution, it requires an overpotential of only 237 mV to reach a current density of 10 mA cm-2 with a small Tafel slope of 38 mV dec-1 and shows prominent long term electrochemical stability. A synergistic effect between highly abundant catalytically active sites on the 3D porous substrate improved the electron transport arising from the presence of highly negative boron, and the high conductivity of the substrate results in an outstanding electrocatalytic activity. The advanced catalytic activity, facile electrode fabrication, and low costs make it a potential oxygen-evolving material, which may be extended to other energy-conversion and storage technologies. PMID- 29797379 TI - A high-resolution anorectal manometry parameter based on integrated pressurized volume: A study based on 204 male patients with constipation and 26 controls. AB - BACKGROUND: Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms. METHODS: A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high-resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed. KEY RESULTS: ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.67 0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52-0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters. CONCLUSIONS AND INFERENCES: The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time. PMID- 29797381 TI - Characteristics of drugs safety signals that predict safety related product information update. AB - PURPOSE: Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016. METHODS: A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI. RESULTS: Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug-event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs <=5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05). CONCLUSIONS: This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates. PMID- 29797382 TI - Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics. AB - BACKGROUND: Serum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. METHODS: Serum levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. KEY RESULTS: Irritable bowel syndrome patients (n = 246) had higher serum levels of IL-1beta, IL-6, IL-8, TNF, and IL-10 compared to HS (n = 21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. CONCLUSIONS & INFERENCES: Serum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS. PMID- 29797377 TI - Vagus nerve stimulation promotes gastric emptying by increasing pyloric opening measured with magnetic resonance imaging. AB - BACKGROUND: Vagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric disorders that are poorly managed by pharmacological treatments and/or dietary changes. Such therapy seems promising as the vagovagal neurocircuitry modulates the enteric nervous system to influence gastric functions. METHODS: Here, the modulatory effects of left cervical VNS on gastric emptying in rats were quantified using a (i) feeding protocol in which the animal voluntarily consumed a postfast, gadolinium-labeled meal and (ii) a non-invasive imaging method to measure antral motility, pyloric activity and gastric emptying based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing pipelines. KEY RESULTS: Vagus nerve stimulation significantly accelerated gastric emptying (sham vs VNS: 29.1% +/- 1.5% vs 40.7% +/- 3.9% of meal emptied per 4 hours), caused a greater relaxation of the pyloric sphincter (sham vs VNS: 1.5 +/- 0.1 vs 2.6 +/- 0.4 mm2 cross-sectional area of lumen), and increased antral contraction amplitude (sham vs VNS: 23.3% +/- 3.0% vs 32.5% +/- 3.0% occlusion), peristaltic velocity (sham vs VNS: 0.50 +/- 0.02 vs 0.67 +/- 0.03 mm s-1 ), but not its contraction frequency (sham vs VNS: 6.1 +/- 0.2 vs 6.4 +/- 0.2 contractions per minute, P = .22). The degree to which VNS relaxed the pylorus was positively correlated with gastric emptying rate (r = .5887, P < .001). CONCLUSIONS & INFERENCES: The MRI protocol employed in this study is expected to enable advanced preclinical studies to understand stomach pathophysiology and its therapeutics. Results from this study suggest an electroceutical treatment approach for gastric emptying disorders using cervical VNS to control the degree of pyloric sphincter relaxation. PMID- 29797383 TI - Evaluating the efficiency of the Dental Teacher system as a digital preclinical teaching tool. AB - AIM: To investigate the use of a preparation evaluation system for enhancing the learning and performance of undergraduate dental students when cutting preparations. MATERIALS AND METHODS: Two groups of eighteen students each were randomly chosen from the fourth year of the dental programme. The task chosen for this study was to make a cavity in preparation for a mesio-occlusal ceramic onlay in a plastic tooth. The dimensions of the cavity were defined, and 2 burs of known size were used for preparation. For assessment, each tooth preparation was scanned with a digital scanner and analysed using the Dental Teacher software. In the control group, a second corrective preparation was made following the supervisor's instructions. In the test group, the second preparation was made based on Dental Teacher analysis. The final cavities were all scanned and assessed by Dental Teacher comparing the similarity of students' onlay cavity preparations to the ideal preparation. All data were recorded and analysed by the software, including cavity depth and width in the occlusal and proximal box, the extent of mesiobuccal cusp reduction and shoulder width around the mesiobuccal cusp. Finally, the data were statistically evaluated using a Wilcoxon matched pairs test and a Mann-Whitney U test. RESULTS: Three of the 6 cavity dimension parameters improved significantly in the test group whilst no improvement was found in the control group. A positive correlation was found between the improvement and the deviation measured for the first preparations, and it was stronger in the test group than in the control group. CONCLUSIONS: The use of Dental Teacher helped students to learn the preparation technique for onlay restorations more efficiently and seems to be a promising and useful method to facilitate their individual performance. Student feedback showed a great demand for digital aids in education. PMID- 29797384 TI - Identifying and integrating patient and caregiver perspectives in clinical practice guidelines for percutaneous renal biopsy. AB - AIMS: Percutaneous renal biopsy is often essential for providing reliable diagnostic and prognostic information for people with suspected kidney disease, however the procedure can lead to complications and concerns among patients. This study aims to identify and integrate patient priorities and perspectives into the Kidney Health Australia - Caring for Australasians with Renal Impairment clinical practice guidelines for renal biopsy, to ensure patient-relevance. METHODS: We convened a workshop, consisting of three simultaneous focus groups and a plenary session, with ten patients who had undergone a renal biopsy and seven caregivers. Topics and outcomes prioritised by patients and their caregivers were compared to those identified by the guideline working group, which was comprised of seven nephrologists. Transcripts and flipcharts were analysed thematically to identify the reasons for participants' choices. RESULTS: In total, 34 topics/outcomes were identified, 14 of which were common to the list of 28 previously identified by the guideline working group. Most of the new topics identified by patients/caregivers were related to communication and education, psychosocial support, and self-management. We identified five themes underpinning the reasons for topic and outcome selection: alleviating anxiety and unnecessary distress, minimising discomfort and disruption, supporting family and caregivers, enabling self-management, and protecting their kidney. A new topic on patient care and education was added to the guideline as a result. CONCLUSIONS: Patient and caregiver involvement in developing guidelines on renal biopsy ensured that their concerns and needs for education, psychosocial support, and self-management were explicitly addressed; enabling a patient-centred approach to renal biopsies. This article is protected by copyright. All rights reserved. PMID- 29797385 TI - Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi. AB - Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6 alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10. PMID- 29797386 TI - Post-Translational Backbone Engineering through Selenomethionine-Mediated Incorporation of Freidinger Lactams. AB - Amino-gamma-lactam (Agl) bridged dipeptides, commonly known as Freidinger lactams, have been shown to constrain peptide backbone topology and stabilize type II' beta-turns. The utility of these links as peptide constraints has inspired new approaches to their incorporation into complex peptides and peptoids, all of which require harsh reaction conditions or protecting groups that limit their use on unprotected peptides and proteins. Herein, we employ a mild and selective alkylation of selenomethionine in acidic aqueous solution, followed by immobilization of the alkylated peptide on to bulk reverse-phase C18 silica and base-induced lactamization in DMSO. The utilization of selenomethionine, which is readily introduced by synthesis or expression, and the mild conditions enable selective backbone engineering in complex peptide and protein systems. PMID- 29797388 TI - Efficient Fabrication of Stable Graphene-Molecule-Graphene Single-Molecule Junctions at Room Temperature. AB - We present a robust approach to fabricate stable single-molecule junctions at room temperature using single-layer graphene as nanoelectrodes. Molecular scale nano-gaps in graphene were generated using an optimized fast-speed feedback controlled electroburning process. This process shortened the time for creating a single nano-gap to be less than one minute while keeping a yield higher than 97 %. To precisely control the gap position and minimize the effects of edge defects and the quantum confinement, extra-narrow grooves were pre-patterned in the graphene structures with oxygen plasma etching. Molecular junctions were formed by bridging the nano-gaps with amino-functionalized hexaphenyl molecules by taking advantage of chemical reactions between the amino groups at the two ends of the molecules and the carboxyl groups at the edges of graphene electrodes. Electronic transport measurements and transition voltage spectroscopy analysis verified the formation of single-molecule devices. First-principles quantum transport calculations show that the highest occupied molecular orbital of hexaphenyl is closer to the Fermi level of the graphene electrodes and thus the devices exhibit a hole-type transport characteristics. Some of these molecular devices remained stable up to four weeks, highlighting the potential of graphene nano-electrodes in the fabrication of stable single-molecule devices at room temperature. PMID- 29797387 TI - Eyelid sebaceous carcinoma in situ presenting as haemorrhagic cyst. PMID- 29797390 TI - GbSOBIR1 confers Verticillium wilt resistance by phosphorylating the transcriptional factor GbbHLH171 in Gossypium barbadense. AB - Receptor-like kinases (RLKs) are important components of plant innate immunity. Although recent studies have revealed that the RLK suppressor of BIR1-1 (SOBIR1) can interact with multiple receptor-like proteins and is required for resistance against fungal pathogens, how the signal is transduced and triggers immune responses remains enigmatic. In this study, we identified a defence-related RLK from Gossypium barbadense (designated GbSOBIR1) and investigated its functional mechanism. Expression of the GbSOBIR1 gene is ubiquitous in cotton plants and is induced by Verticillium dahliae inoculation. Knock-down of GbSOBIR1 by virus induced gene silencing resulted in attenuated resistance of cotton plants to V. dahliae, while heterologous overexpression of GbSOBIR1 in Arabidopsis improves resistance. We also found that the kinase region of GbSOBIR1 interacts with a basic helix-loop-helix (bHLH) transcription factor identified as GbbHLH171 in a yeast-two-hybrid screen. GbbHLH171 could interact with and be phosphorylated by GbSOBIR1 in vitro and in vivo and contributes positively to the resistance of cotton against V. dahliae. Furthermore, we found that this phosphorylation is essential to the transcriptional activity and functional role of GbbHLH171. We also show by spectrometric analysis and site-directed mutagenesis that Ser413 is the GbSOBIR1-mediated phosphorylation site of GbbHLH171. These results demonstrate that GbSOBIR1 interacts with GbbHLH171 and plays a critical role in cotton resistance to V. dahliae. PMID- 29797389 TI - The management of type 2 diabetes with fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy (insulin glargine U100 plus insulin aspart): A short-term cost-effectiveness analysis in the UK setting. AB - AIM: To evaluate the cost-effectiveness of IDegLira versus basal-bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. METHODS: A Microsoft Excel model was used to evaluate the cost-utility of IDegLira versus BBT over a 1-year time horizon. Clinical input data were taken from the treat-to-target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event-related disutilities were taken from published sources. Extensive sensitivity analyses were performed. RESULTS: IDegLira was associated with an improvement of 0.05 quality-adjusted life years (QALYs) versus BBT, due to reductions in non-severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost-effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. CONCLUSIONS: IDegLira is a cost-effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK. PMID- 29797392 TI - Comment on Pacheco-Gonzalez et al. PMID- 29797391 TI - Laparoscopic-assisted techniques in overcoming bulky sigmoid colon cancer - a video vignette. PMID- 29797393 TI - Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease related advanced fibrosis. AB - BACKGROUND & AIM: Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score. RESULTS: Of the 6738 participants (mean age 46.3 years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively). CONCLUSIONS: In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors. PMID- 29797395 TI - The diversity of neutrophil inclusion bodies in fulminant sepsis. PMID- 29797394 TI - Blood pressures immediately following ischemic strokes are associated with cerebral perfusion and neurologic function. AB - The optimal range of blood pressure levels in the early phase of ischemic stroke with hypertension is still controversial. Based on our stroke registry database, we explored the relationship between blood pressure levels and cerebral perfusion in the early phase of ischemic stroke with hypertension and neurofunctional recovery at 3 months after stroke. Total 732 stroke patients with hypertension were finally analyzed. Patients were divided into quintiles according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) to perform multivariable logistic regression to analyze their relation with neurofunctional recovery, respectively. The cerebral perfusion levels displayed a reverse "U" shape curve with the change of blood pressure levels. Sufficient estimated cerebral blood flow (ECBF) in the early phase of ischemic stroke was associated with good neurofunctional recovery at 3 months after stroke. The best neurofunctional recovery was observed in the middle quintiles with SBP at 161 to 177 mm Hg and DBP at 103 to 114 mm Hg, respectively. So maintaining appropriate blood pressure levels in the early phase of ischemic stroke might be beneficial to cerebral perfusion and neurofunctional recovery. PMID- 29797396 TI - Technical note: A 3D-printed phantom for routine accuracy check of Gamma Knife Icon HDMM system. AB - PURPOSE: To report a novel 3D-printed device ("SH phantom") that is designed for routine accuracy check of the Gamma Knife Icon High Definition Motion Management (HDMM) system. METHODS: SH phantom was designed using tinkerCAD software and printed on a commercial 3D printer. We evaluated the SH phantom on our Gamma Knife Icon unit regarding its usability and accuracy for routine HDMM QA. RESULTS: Single-axis and multiple-axis measurements validated the SH phantom design and implementation. An HDMM QA accuracy of 0.22 mm or better along single axis was found using SH phantom. CONCLUSIONS: The SH phantom proved to be a quick and simple tool to use to perform the HDMM system QA. The SH phantom was tested successfully and adopted by us as part of monthly QA for the Gamma Knife Icon. PMID- 29797397 TI - Projecting the current and future potential global distribution of Hyphantria cunea (Lepidoptera: Arctiidae) using CLIMEX. AB - BACKGROUND: The international invasive and quarantined defoliating insect Hyphantria cunea Drury (Lepidoptera: Arctiidae) causes huge ecological and economic losses in the world. Furthermore, future climate change may alter the distribution of H. cunea and aggravate the damage. In the present study, we used CLIMEX to project the potential global distribution of H. cunea according to both historical climate data (1961-1990) and future climate warming estimates (2011 2100) to define the impact of climate change. RESULTS: Under the historical climate scenario, we found that H. cunea can survive on every continent, and temperature is the main factor that limits its establishment. With climate change, suitability will increase in middle and high latitude regions, while decrease in the low latitude regions. Moreover, tropic regions will be the most sensitive to climate change impacts for the pest to survive. The impacts of climate change will also increase over time, whether they be positive impacts or negative impacts. CONCLUSION: The projected potential distributions provide a theoretical basis for quarantine and control strategies for the management of this pest in each country. Furthermore, these results provide substantial guidance for studies of the effects of climate change on other major forest pests. (c) 2018 Society of Chemical Industry. PMID- 29797399 TI - Repressed Beauveria bassiana infections in Delia antiqua due to associated microbiota. AB - BACKGROUND: Insects form both mutualistic and antagonistic relationships with microbes, and some antagonistic microbes have been used as biocontrol agents (BCAs) in pest management. Contextually, BCAs may be inhibited by beneficial insect symbionts, which can become potential barriers to entomopathogen-dependent pest biocontrol. Using the symbioses formed by one devastating dipteran pest, Delia antiqua, and its associated microbes as a model system, we sought to determine whether the antagonistic interaction between BCAs and microbial symbionts could affect the outcome of entomopathogen-dependent pest biocontrol. RESULTS: The result showed that in contrast to non-axenic D. antiqua larvae, i.e., onion maggots, axenic larvae lost resistance to the entomopathogenic Beauveria bassiana, and the re-inoculation of microbiota increased the resistance of axenic larvae to B. bassiana. Furthermore, bacteria frequently isolated from larvae, including Citrobacter freundii, Enterobacter ludwigii, Pseudomonas protegens, Serratia plymuthica, Sphingobacterium faecium and Stenotrophomonas maltophilia, suppressed B. bassiana conidia germination and hyphal growth, and the re-inoculation of specific individual bacteria enhanced the resistance of axenic larvae to B. bassiana. CONCLUSION: Bacteria associated with larvae, including C. freundii, E. ludwigii, P. protegens, S. plymuthica, S. faecium and S. maltophilia, can inhibit B. bassiana infection. Removing the microbiota can suppress larval resistance to fungal infection. (c) 2018 Society of Chemical Industry. PMID- 29797400 TI - Comments on a new classification, treatment algorithm and prognosis-estimating system for ileosigmoid knotting: the role of endoscopic treatment. PMID- 29797398 TI - Apolipoprotein E region molecular signatures of Alzheimer's disease. AB - Although the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age-related diseases characteristic for postreproductive period, is hampered by the undefined role of evolution in establishing molecular mechanisms of such diseases. This uncertainty is inevitable source of natural-selection-free genetic heterogeneity in predisposition to ADs. We performed first large-scale analysis of linkage disequilibrium (LD) structures characterized by 30 polymorphisms from five genes in the APOE 19q13.3 region (BCAM, NECTIN2, TOMM40, APOE, and APOC1) in 2,673 AD affected and 16,246 unaffected individuals from five cohorts. Consistent with the undefined role of evolution in age-related diseases, we found that these structures, being highly heterogeneous, are significantly different in subjects with and without ADs. The pattern of the difference represents molecular signature of AD comprised of single nucleotide polymorphisms (SNPs) from all five genes in the APOE region. Significant differences in LD in subjects with and without ADs indicate SNPs from different genes likely involved in AD pathogenesis. Significant and highly heterogeneous molecular signatures of ADs provide unprecedented insight into complex polygenetic predisposition to ADs in the APOE region. These findings are more consistent with a complex haplotype than with a single genetic variant origin of ADs in this region. PMID- 29797401 TI - Cannibalism by erythroleukaemic blasts. PMID- 29797402 TI - Cost-effectiveness of using kidneys from hepatitis C nucleic acid test-positive donors for transplantation in hepatitis C-negative recipients. AB - Kidneys from deceased donors who are hepatitis C virus (HCV) nucleic acid test positive are infrequently used for transplantation in HCV-negative patients due to concerns about disease transmission. With the development of direct-acting antivirals (DAAs) for HCV, there is now potential to use these kidneys in HCV negative candidates. However, the high cost of DAAs poses a challenge to adoption of this strategy. We created a Markov model to examine the cost-effectiveness of using deceased donors infected with HCV for kidney transplantation in uninfected waitlist candidates. In the primary analysis, this strategy was cost saving and improved health outcomes compared to remaining on the waitlist for an additional 2 or more years to receive a HCV-negative transplant. The strategy was also cost effective with an incremental cost-effectiveness ratio of $56 018 per quality adjusted life year (QALY) from the payer perspective, and $4647 per QALY from the societal perspective, compared to remaining on the waitlist for 1 additional year. The results were consistent in 1-way and probabilistic sensitivity analyses. We conclude that the use of kidneys from deceased donors with HCV infection is likely to lead to improved clinical outcomes at reduced cost for HCV negative transplant candidates. PMID- 29797403 TI - Serine/threonine protein phosphatase 5 is a potential therapeutic target in cholangiocarcinoma. AB - BACKGROUND & AIMS: Few molecules are currently verified to be actionable drug targets in cholangiocarcinoma (CCA). Serine/threonine protein phosphatase 5 (PP5) dysregulation is related to several malignancies. However, the role of PP5 in CCA is poorly defined. METHODS: Colony and tumorsphere formation assays were conducted to establish the role of PP5 in CCA tumorigenesis. Cantharidin (CTD) and norcantharidin (NCTD), both potent PP5 inhibitors, were used in in vitro and in vivo experiments to validate the potential therapeutic role of PP5. RESULTS: Increased cell growth, colony formation and tumorsphere formation were observed in PP5-overexpressing CCA cells, whereas PP5 knockdown by shRNA decreased cell growth and colony formation. Tumours from HuCCT1 xenograft-bearing mice treated with PP5-shRNA showed decreased growth and increased AMP-activated protein kinase (AMPK) phosphorylation. Furthermore, CTD treatment decreased cell viability, reduced PP5 activity and enhanced AMPK phosphorylation in CCA cell lines. Overexpressing PP5 or enhancing PP5 activity suppressed AMPK phosphorylation and decreased CTD-induced cell death. Suppressing p-AMPK with siRNA or inhibitors also decreased CTD-induced cell death, suggesting a pivotal role for PP5-AMPK cascades in CCA. Immunoprecipitation revealed that PP5 interacted with AMPK. Importantly, treatment of HuCCT1 xenograft-bearing mice with NCTD, a CTD analogue with a lower systemic toxicity in vivo, suppressed PP5 activity, increased p-AMPK and reduced tumour volume. CONCLUSIONS: Protein phosphatase 5 negatively regulates AMPK phosphorylation and contributes to CCA aggressiveness; thus, PP5 may be a potential therapeutic target in CCA. PMID- 29797405 TI - Fusarium species and moniliformin occurrence in sorghum grains used as ingredient for animal feed in Argentina. AB - BACKGROUND: A survey on Fusarium species and moniliformin (MON) occurrence in sorghum grains collected from one of the main sorghum-producing areas of Argentina was conducted. Also, growth of F. thapsinum, one of the main sorghum pathogens, and MON production under different water activity (aw ) conditions on a sorghum-based medium were determined. RESULTS: Infection of sorghum grains by Fusarium species ranged from 82.5 to 99%; closely related species F. verticillioides, F. thapsinum and F. andiyazi were the most frequently recovered, followed by F. proliferatum and F. subglutinans. By sequencing a portion of the translation elongation factor-1alpha (TEF-1alpha) gene and by maximum parsimony analysis, F. verticillioides and closely related species were identified as F. thapsinum, F. andiyazi and F. verticillioides. Species within the F. graminearum species complex (FGSC) were isolated in high frequency. Maximum growth rates of 12 F. thapsinum strains were obtained at 0.995 aw . All evaluated strains were able to produce MON at all aw values tested, but MON production was higher at 0.995-0.982 aw . MON was detected in 41% of the samples at levels ranging from 363.2 to 914.2 ug kg-1 . CONCLUSION: This study provides new data on the occurrence of Fusarium species in sorghum grains destined for animal consumption in Argentina. The production of MON at different aw values showed that the toxin can be produced under field conditions. The risk to livestock exposed to daily low levels of MON associated with the toxin occurrence in the sorghum grains analyzed is unknown. (c) 2018 Society of Chemical Industry. PMID- 29797406 TI - Meningococcal epiglottitis in a healthy adult patient: The first documented case in Australia. PMID- 29797404 TI - Stillbirth rates in 20 countries of Latin America: an ecological study. AB - OBJECTIVE: To describe country-level stillbirth rates and their change over time in Latin America, and to measure the association of stillbirth rates with socio economic and health coverage indicators in the region. DESIGN: Ecological study. SETTING: 20 countries of Latin America. POPULATION OR SAMPLE: Aggregated data from pregnant women with countries as units of analysis. METHODS: We used stillbirth estimates, and socio-economic and healthcare coverage indicators reported from 2006 to 2016 from UNICEF, United Nations Development Programme and World Bank datasets. We calculated Spearman's correlation coefficients between stillbirths rates and socioeconomic and health coverage indicators. MAIN OUTCOME MEASURES: National estimates of stillbirth rates in each country. RESULTS: The estimated stillbirth rate for Latin America for 2015 was 8.1 per 1000 births (range 3.1-24.9). Seven Latin America countries had rates higher than 10 stillbirths per 1000 births. The average annual reduction rate for the region was 2% (range 0.1-3.8%), with the majority of Latin America countries ranging between 1.5 and 2.5%. National stillbirth rates were correlated to: women's schooling (rS = -0.7910), gross domestic product per capita (rS = -0.8226), fertility rate (rS = 0.6055), urban population (rS = -0.6316), and deliveries at health facilities (rS = -0.6454). CONCLUSIONS: Country-level estimated stillbirth rates in Latin America varied widely in 2015. The trend and magnitude of reduction in stillbirth rates between 2000 and 2015 was similar to the world average. Socio-economic and health coverage indicators were correlated to stillbirth rates in Latin America. TWEETABLE ABSTRACT: Stillbirth rates decreased in Latin America but remain relatively high, with wide variations among countries. PMID- 29797407 TI - Visibility of bony structures around hip prostheses in dual-energy CT: With or without metal artefact reduction software. AB - INTRODUCTION: The development of dual-energy CT and metal artefact reduction software provides a further chance of reducing metal-related artefacts. However, there have been only a few studies regarding whether MARs practically affect visibility of structures around a metallic hip prosthesis on post-operative CT evaluation. METHODS: Twenty-seven patients with 42 metallic hip prostheses underwent DECT. The datasets were reconstructed with 70, 90 and 110 keV with and without MARs. The areas were classified into 10 zones according to the reference zone. All the images were reviewed in terms of the severity of the beam-hardening artefacts, differentiation of the bony cortex and trabeculae and visualization of trabecular patterns with a three-point scale. The metallic screw diameter was measured in the acetabulum with 110 keV images. RESULTS: The scores were the worst on 70 keV images without MARs [mean scores:1.84-4.22 (p < 0.001-1.000)]. The structures in zone II were best visualized on 110 keV (p < 0.001-0.011, mean scores: 2.86-5.22). In other zones, there is general similarity in mean scores whether applying MARs or not (p < 0.001-0.920). The mean diameter of the screw was 5.85 mm without MARs and 3.44 mm with MARs (mean reference diameter: 6.48 mm). CONCLUSION: The 110 keV images without MARs are best for evaluating acetabular zone II. The visibility of the bony structures around the hip prosthesis is similar in the other zones with or without MARs regardless of keV. MARS may not be needed for the evaluation of the metallic hip prosthesis itself at sufficient high-energy levels; however, MARS still has a role in the evaluation of other soft tissues around the prosthesis. PMID- 29797408 TI - Interaction between quinoline yellow and human serum albumin: spectroscopic, chemometric and molecular docking studies. AB - BACKGROUND: Quinoline yellow (QY), a synthetic colourant widely used in the food industry, has caused extensive concerns because of its potentially harmful effects on human health. In the present work, the interactions between QY and human serum albumin (HSA) were characterized by multiple spectroscopic methods, a chemometric algorithm, and molecular modelling studies. RESULTS: The concentration profiles and pure spectra obtained for the components (QY, HSA and QY-HSA complex) from analyses of the expanded UV-visible absorption data matrices by multivariate curve resolution alternating least squares confirmed the QY-HSA interaction process. QY quenched the fluorescence of HSA through formation of a QY-HSA complex that was stabilized by moderate affinity. Hydrophobic forces and hydrogen bonding play major roles in the binding of QY to HSA. Site-specific marker-induced displacement results suggest that QY binds to subdomain IIA of HSA. This was corroborated by the molecular docking results. Decreases in HSA surface hydrophobicity and free sulfhydryl group content indicate that QY causes a contraction of the peptide strand in HSA, hiding the hydrophobic patches of the protein. Analyses by UV-visible absorption, circular dichroism, and three dimensional fluorescence spectroscopy found that QY causes microenvironmental perturbations around the fluorophores and secondary structure changes in HSA. CONCLUSION: This work shows that QY binds to HSA, affecting its structural and functional properties, and provides new insights into the binding mechanism and a comprehensive understanding of the toxicity of QY to biological processes. (c) 2018 Society of Chemical Industry. PMID- 29797409 TI - Effects of humidity on skin friction against medical textiles as related to prevention of pressure injuries. AB - Sustained pressure, shear forces, and friction, as well as elevated humidity/moisture, are decisive physical factors in the development of pressure injuries (PIs). To date, further research is needed in order to understand the influence of humidity and moisture on the coefficient of friction (COF) of skin against different types of medical textiles. The aim of this work was to investigate the effects of moisture caused by sweat, urine, or saline on the resulting COF of skin against different textiles used in the medical setting in the context of PI prevention. For that purpose, we performed physical measurements of static COFs of porcine skin followed by finite element (FE) computational modelling in order to illustrate the effect of increased COF at the skin on the resulting strains and stresses deep within the soft tissues of the buttocks. The COF of dry skin obtained for the 3 textiles varied between 0.59 (adult diaper) and 0.91 (polyurethane dressing). In addition, the COF increased with the added moisture in all of the tested cases. The results of the FE simulations further showed that increased COF results in elevated strain energy density and shear strain values in the skin and deeper tissues and, hence, in an increased risk for PI development. We conclude that moisture may accelerate PI formation by increasing the COF between the skin and the medical textile, regardless of the type of the liquid that is present. Hence, reduction of the wetness/moisture between the skin and fabrics in patients at a high risk of developing PIs is a key measure in PI prevention. PMID- 29797410 TI - A combination of the on-treatment FIB-4 and alpha-foetoprotein predicts clinical outcomes in cirrhotic patients receiving entecavir. AB - BACKGROUND & AIMS: This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy. METHODS: We enrolled 481 nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months. RESULTS: The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality. CONCLUSION: The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy. PMID- 29797411 TI - Transsphenoidal surgery: accuracy of an image-guided neuronavigation system to approach the pituitary fossa (sella turcica). AB - OBJECTIVE: To determine the accuracy of locating the pituitary fossa with the Brainsight neuronavigation system by determining the mean target error of the rostral (tuberculum sellae) and caudal (dorsum sellae) margins of the pituitary fossa. STUDY DESIGN: Experimental cadaveric study. ANIMALS: Ten canine cadavers. METHODS: Computed tomography (CT) and MRI were performed on each cadaver with fiducials in place. Images were saved to the neuronavigation computer and used to plan the drilling approach. The cadavers were placed in the surgical head clamp of the Brainsight system and positioned for a transsphenoidal approach. On the basis of the planning, 2 localization points were drilled, 1 each at the rostral and caudal margins of the pituitary fossa, and CT was repeated. Error was assessed from the difference in millimeters between the targets identified during Brainsight planning and the actual location of the 2 points drilled on each cadaver skull as identified by postdrilling CT. RESULTS: The rostral and caudal margins of the pituitary fossa provided 2 target points per cadaver. The median target error (interquartile range) for all target sites (n = 20) was 3.533 mm (range, 2.013-4.745). CONCLUSION: This stereotactic system allowed the surgeon to locate the rostral and caudal margins of the pituitary fossa with clinically acceptable accuracy and confidence. CLINICAL SIGNIFICANCE: Using the Brainsight neuronavigation system for localization during transsphenoidal hypophysectomy may decrease morbidity and surgical time. PMID- 29797412 TI - Egg proteins: fractionation, bioactive peptides and allergenicity. AB - Eggs are an important source of macro and micronutrients within the diet, comprised of proteins, lipids, vitamins, and minerals. They are constituted by a shell, the white (containing 110 g kg-1 proteins: ovalbumin, ovotransferrin, ovomucoid, lysozyme and ovomucin), and the yolk (containing 150-170 g kg-1 proteins: lipovitellins, phosvitin, livetins, and low-density lipoproteins). Owing to their nutritional value and biological characteristics, both the egg white and yolk proteins are extensively fractionated using different techniques (e.g., liquid chromatography, ultrafiltration, electrophoresis, and chemical precipitation), in which liquid chromatography is the most commonly used technique to obtain individual proteins with high protein recovery and purity to develop novel food products. However, concerns over allergenic responses induced by certain egg proteins (e.g., ovomucoid, ovalbumin, ovotransferrin, lysozyme, alpha-livetin, and lipoprotein YGP42) limit their widespread use. As such, processing technologies (e.g., thermal processing, enzymatic hydrolysis, and high pressure treatment) are investigated to reduce the allergenicity by conformational changes. In addition, biological activities (e.g., antioxidant, antimicrobial, antihypertensive, and anticancer activities) associated with egg peptides have received more attention, in which enzyme hydrolysis is demonstrated as a promising way to break polypeptides sequences and produce bioactive peptides to provide nutritional and therapeutic benefits for human health. (c) 2018 Society of Chemical Industry. PMID- 29797413 TI - Evaluation of microbial contamination of canine plasma eyedropper bottles following clinical use in canine patients. AB - OBJECTIVE: To investigate microbial contamination of canine plasma eye drops when used clinically and to compare the effect of two different eyedropper bottles on contamination rate. METHODS: Forty-six bottles containing plasma were randomly dispensed for use on 42 dogs with ulcerative keratitis. Of these, 23 were standard eyedropper bottles and 23 were Novelia(r) bottles designed to prevent contamination. After use for up to 2 weeks, samples for bacterial culture were obtained from a drop of plasma, the bottle tip, the plasma inside the bottle, and the corneal surface. Fungal culture was performed from a drop of plasma. RESULTS: The overall microbial contamination rate was 17.4% (8/46 bottles); however, only one bottle had growth from the plasma inside the bottle. There was a lower contamination rate of Novelia(r) bottles (3/23 = 13.0%) compared to standard bottles (5/23 = 21.7%), but this difference was not statistically significant (P = .57). There were also no significant differences in contamination rate of bottles used greater than 7 days compared to less than or equal to 7 days, or in bottles used greater than 4 times daily compared to 4 times daily or less. Three corneal samples (6.5%) had bacterial growth, but none matched contamination from the bottles. CONCLUSIONS: Novelia(r) bottles may decrease contamination of plasma eye drops used clinically. However, while microbial contamination of plasma bottles was documented, no clinically relevant complications were observed. This study supports safe use of plasma eye drops for up to 2 weeks when refrigerated and dispensed from either Novelia(r) or standard eyedropper bottles. PMID- 29797415 TI - Influence of maternal obesity on Bishop Score and failed induction of labour: A retrospective cohort study in a regional tertiary centre. AB - BACKGROUND: Maternal obesity is a growing health concern that has previously been associated with increased need for induction of labour (IOL) and caesarean section (CS) rates. Currently, limited evidence explores the influence of maternal body mass index (BMI) on Bishop Score (BS) and outcome of IOL. This study hypothesises that maternal obesity will lead to a lower BS at presentation, higher rates of failed IOL, and increased CS rates. AIMS: To explore the influence of maternal obesity on BS and likelihood of failed IOL. METHODS: A retrospective cohort analysis was conducted of all live, term, singleton, cephalic deliveries initiated with IOL across normal BMI (18.00-24.99), overweight BMI (25.00-29.99), and obese BMI (>30.00) at the Townsville Hospital and Health Service (THHS) between July 2011 to June 2016. Student's t-test, chi2 test, and binary logistic regression were used for statistical analysis. BS and failed IOL, defined as CS with cervical dilatation <3 cm, were the primary outcome measures. Delivery mode was the secondary outcome measure. RESULTS: A total of 1543 women were included, 678 with normal BMI, 370 with overweight BMI, and 495 with obese BMI. Obese women are more likely to have a low BS (<5) at presentation (unadjusted odds ratio (OR) 1.5 (1.1-2.0), P < 0.05), an increased rate of failed IOL (adjusted OR (aOR) 1.6 (1.0-2.5), P < 0.05) and increased CS rate (aOR 1.1 (1.0-1.9), P < 0.05), compared to normal weight women. CONCLUSIONS: Maternal obesity is associated with a lower BS, more difficult IOL process, and increased risk of failed IOL and CS. PMID- 29797417 TI - Lycium barbarum Polysaccharide Supplementation Improves Alcoholic Liver Injury in Female Mice by Inhibiting Stearoyl-CoA Desaturase 1. AB - SCOPE: Lycium barbarum polysaccharide (LBP) is a water fraction of wolfberry, which has been demonstrated to possess a hepatoprotective effect in several liver disease models. However, the anti-alcoholic liver disease (anti-ALD) mechanism of LBP has not been investigated thoroughly. Its protective effects on both male and femal mice are investigated in the current study. METHODS AND RESULTS: A chronic ethanol-fed ALD in vivo model is applied to study the effect of LBP in both male and female mice. It is observed that ethanol causes more severe liver injury in female than male mice, and the ameliorative effects of LBP are also more significant in female mice, which are impaired after complete bilateral oophorectomy. The hepatic SCD1 expression is found to be positively correlated with the severity of the liver damage and the main mediator of LBP inducer of protection. The AMPK-CPT pathway is also activated by LBP to rebalance the dysregulated lipid metabolism during ALD development. By using concurrent sodium palmitate and an ethanol-induced in vitro cell damage model in AML-12 cell line, it is characterized that LBP directly interacts with ERalpha instead of ERbeta to activate the SCD1-AMPK-CPT pathway. CONCLUSIONS: LBP is an effective and safe hepatoprotective agent against ALD primarily through the SCD1-AMPK-CPT pathway after ERalpha agonist. PMID- 29797416 TI - Risk factors for pneumonitis in patients treated with anti-programmed death-1 therapy: A case-control study. AB - Immune checkpoint blockade-related pneumonitis is a rare but potentially life threatening adverse effect, but its risk factors are not completely understood. This case-control study was conducted to identify pneumonitis risk factors in patients treated with anti-PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti-PD-1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity-score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti-PD-1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51-7.39), 2.86 (1.45-5.64) and 2.73 (1.40-5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti-PD-1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti-PD-1 therapy to optimize clinical safety and efficacy. PMID- 29797414 TI - Droplet microfluidics for high-sensitivity and high-throughput detection and screening of disease biomarkers. AB - Biomarkers are nucleic acids, proteins, single cells, or small molecules in human tissues or biological fluids whose reliable detection can be used to confirm or predict disease and disease states. Sensitive detection of biomarkers is therefore critical in a variety of applications including disease diagnostics, therapeutics, and drug screening. Unfortunately for many diseases, low abundance of biomarkers in human samples and low sample volumes render standard benchtop platforms like 96-well plates ineffective for reliable detection and screening. Discretization of bulk samples into a large number of small volumes (fL-nL) via droplet microfluidic technology offers a promising solution for high-sensitivity and high-throughput detection and screening of biomarkers. Several microfluidic strategies exist for high-throughput biomarker digitization into droplets, and these strategies have been utilized by numerous droplet platforms for nucleic acid, protein, and single-cell detection and screening. While the potential of droplet-based platforms has led to burgeoning interest in droplets, seamless integration of sample preparation technologies and automation of platforms from biological sample to answer remain critical components that can render these platforms useful in the clinical setting in the near future. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease. PMID- 29797419 TI - New approach to predict photoallergic potentials of chemicals based on murine local lymph node assay. AB - Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA. Photoallergic potential of chemicals was evaluated by comparing lymph node cell proliferation among groups treated with chemicals with minimal effect levels of skin sensitization and skin phototoxicity under UV irradiation (UV+) or non-UV irradiation (UV-). A case showing significant difference (P < .05) in lymph node cell proliferation rates between UV- and UV+ groups was considered positive for photoallergic reaction. After testing 13 chemicals, seven human photoallergens tested positive and the other six, with no evidence of causing photoallergic dermatitis or UV absorption, tested negative. Among these chemicals, both doxycycline hydrochloride and minocycline hydrochloride were tetracycline antibiotics with different photoallergic properties, and the new method clearly distinguished between the photoallergic properties of these chemicals. These findings suggested high predictability of our method; therefore, it is promising and effective in predicting human photoallergens. PMID- 29797418 TI - Resuscitative hysterotomy: Training for this rare life-saving intervention. PMID- 29797421 TI - Risk factors for opioid overdose among hospitalized patients. AB - WHAT IS KNOWN AND OBJECTIVE: Hospitalized patients are at risk for opioid overdose. Little is known about the risk factors for these events. METHOD: Opioid overdose cases were identified by naloxone orders in computerized order entry system from a single institution. For each case, two controls were randomly selected. Data were collected on factors including age, gender, weight, opioid dose, route of administration, concomitant CNS depressants, renal function and comorbid conditions. RESULTS AND DISCUSSION: Between 2010 and 2013, we identified 44 cases of opioid overdose (OD), none of which were fatal, and matched these to 88 controls (no OD). Patients with a history of substance use disorder were excluded from the study. Factors associated with opioid overdose included age of 65 or older (40.9% OD vs 29.5% no OD, P = .026), being in an ICU (MICU/CICU 27.3% OD vs. 3.4% no OD, P < .001; SICU 18.1% OD vs 5.7% no OD, P = .031) and renal impairment (eGFR <=60, 50.0% OD vs 28.4% no OD, P = .034). Total 24-hour opioid dose was lower in OD group, but the difference was not statistically significant (71.9 vs 107.2 mg morphine equivalent, P = .116). OD cases were more likely to have received concomitant CNS depressants, but the difference was statistically significant only for those who received 3 or more (15.9% OD vs 0% no OD, P = <.001). Heart disease was the only comorbidity significantly associated with an increased risk of opioid overdose (43.2% vs 20.5%, P = .025). Patient's BMI, duration of opioid use, route of administration and history of COPD and/or psychiatry were not associated with opioid overdoses. WHAT IS NEW AND CONCLUSION: Among hospitalized patients, risk factors of opioid overdose include age of 65 or greater, being in an ICU, renal impairment and concomitant administration of CNS depressant medications. These findings may help with the development and implementation of measures to prevent overdose. PMID- 29797420 TI - Prospective associations of breastfeeding and smoking cessation among low-income pregnant women. AB - Although low-income pregnant women have high rates of smoking and low rates of breastfeeding, few studies have examined prospective associations between these risk factors in community samples. Doing so may help improve breast-feeding support programs in this population. We used a secondary analysis of 247 low income pregnant smokers in Memphis, Tennessee, who were interviewed up to 4 times (twice during pregnancy and twice through 6 months postpartum). Smoking cessation during prepartum and postpartum was defined as a self-report of not smoking for >=1 week and an expired carbon monoxide level of <10 ppm. Multivariable logistic regression analyses were used to determine whether intent to breastfeed was associated with smoking cessation and whether smoking cessation was associated with actual breastfeeding. Models were adjusted for sociodemographic, pregnancy related, and smoking-related confounders. Thirty-nine percent of participants intended to breastfeed, and 38% did so. Women who intended to breastfeed were 2 times more likely to quit smoking prepartum (adjusted OR = 1.99, 95% CI [1.06, 3.74]), but not postpartum (adjusted OR = 1.27, 95% CI [0.57, 2.84]). Quitting smoking at baseline and during pregnancy was associated with subsequent breastfeeding (adjusted OR 2.27, 95% CI [1.05, 4.94] and adjusted OR = 2.49, 95% CI [1.21, 5.11]). Low-income women who intended to breastfeed were more likely to quit smoking during pregnancy and those who quit smoking at baseline and prepartum were more likely to breastfeed. Simultaneously supporting breastfeeding and smoking cessation may be very useful to change these important health behaviours among this high-risk population. PMID- 29797422 TI - Chemically Modified Polyaniline for the Detection of Volatile Biomarkers of Minimal Sensitivity to Humidity and Bending. AB - Flexible sensors can be widely used in future wearable devices to monitor people's health states. However, most of the sensors are sensitive to humidity and bending effects, limiting their application in a real-world environment. A new strategy is proposed for obtaining flexible sensors with good tolerance to humidity. By integrating a hydrophobic layer on the surface of doped polyaniline, a flexible sensor that can resist water response with a concentration up to 350 ppm is developed. Good resilience against mechanical bending is also achieved in this flexible sensor. These results may trigger a renaissance in flexible sensor applications for disease diagnosing by wearable devices. PMID- 29797423 TI - Increased virulence in the locust-specific fungal pathogen Metarhizium acridum expressing dsRNAs targeting the host F1 F0 -ATPase subunit genes. AB - BACKGROUND: Metarhizium acridum is a host-specific fungal pathogen with great potential for locust control. However, the slow killing action of M. acridum has impeded its widespread application. To enhance fungal virulence, we constructed transgenic M. acridum strains that express double-stranded (ds)RNAs targeting the genes of the F1 F0 -ATP synthase alpha and beta subunits in Locusta migratoria. RESULTS: The two host genes were transcriptionally suppressed in L. migratoria nymphs (instar V) infected by RNA interference (RNAi) strains targeting one or two subunit genes of the host ATP synthase, followed by reduced ATPase activity and ATP synthesis. Consequently, the RNAi strain targeting both subunit genes displayed high virulence that was 3.7-fold that in the wild-type strain. CONCLUSION: Our results demonstrate that dsRNA expression in M. acridum can cause host RNA silencing during infection and greatly enhances the fungal virulence through interference with critical host genes, highlighting a new strategy for augmentation of fungal virulence against insect pests. (c) 2018 Society of Chemical Industry. PMID- 29797424 TI - Oculocardiac reflex: 'My heart just stopped'. PMID- 29797425 TI - Intracranial, extraneural ectopic lymph node in a bovine (Bos taurus). AB - The brain from a field necropsied 8-month-old feedlot heifer presenting with an acute history of depression, lethargy, dyspnoea and anorexia was evaluated grossly and by histopathology. The meninges overlying the left cerebral hemisphere contained a 12 * 26 * 32 mm, dark red, soft, ovoid mass. Histologic examination of this tissue revealed a well-organized lymph node with normal architecture. Organization of reactive lymphoid tissue resembling normal lymph node architecture may occur under chronic stimulation. However, there are no known aggregates of lymphoid tissue present within the cranial vault in any veterinary species. This is the first reported case of an intracranial ectopic lymph node in any species. PMID- 29797427 TI - Aquaporin-2 plays an important role in water transportation through the bladder wall in rats. AB - AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 +/- 0.00 vs 0.83 +/- 0.08 mL, 157.80 +/- 1.30 vs 146.8 +/- 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 +/- 0.00 and 0.99 +/- 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 +/- 2.4 vs 143.6 +/- 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function. PMID- 29797426 TI - Modeling individualized coefficient alpha to measure quality of test score data. AB - Individualized coefficient alpha is defined. It is item and subject specific and is used to measure the quality of test score data with heterogenicity among the subjects and items. A regression model is developed based on 3 sets of generalized estimating equations. The first set of generalized estimating equation models the expectation of the responses, the second set models the response's variance, and the third set is proposed to estimate the individualized coefficient alpha, defined and used to measure individualized internal consistency of the responses. We also use different techniques to extend our method to handle missing data. Asymptotic property of the estimators is discussed, based on which inference on the coefficient alpha is derived. Performance of our method is evaluated through simulation study and real data analysis. The real data application is from a health literacy study in Hunan province of China. PMID- 29797428 TI - A novel HLA variant, HLA-C*03:376, detected by next generation sequencing. AB - HLA-C*03:376 differs from HLA-C*03:04:01 in exon 6 by a single nucleotide substitution. PMID- 29797429 TI - Factors contributing to the failure of humidified high-flow nasal cannulae. PMID- 29797430 TI - Refined 4-group classification of left ventricular hypertrophy based on ventricular concentricity and volume dilatation outlines distinct noninvasive hemodynamic profiles in a large contemporary echocardiographic population. AB - BACKGROUND: Left ventricular hypertrophy (LVH) may reflect a wide variety of physiologic and pathologic conditions. Thus, it can be misleading to consider all LVH to be homogenous or similar. Refined 4-group classification of LVH based on ventricular concentricity and dilatation may be identified. To determine whether the 4-group classification of LVH identified distinct phenotypes, we compared their association with various noninvasive markers of cardiac stress. METHODS: Cohort of unselected adult outpatients referred to a seven tertiary care echocardiographic laboratory for any indication in a 2-week period. We evaluated the LV geometric patterns using validated echocardiographic indexation methods and partition values. RESULTS: Standard echocardiography was performed in 1137 consecutive subjects, and LVH was found in 42%. The newly proposed 4-group classification of LVH was applicable in 88% of patients. The most common pattern resulted in concentric LVH (19%). The worst functional and hemodynamic profile was associated with eccentric LVH and those with mixed LVH had a higher prevalence of reduced EF than those with concentric LVH (P < .001 for all). CONCLUSIONS: The new 4-group classification of LVH system showed distinct differences in cardiac function and noninvasive hemodynamics allowing clinicians to distinguish different LV hemodynamic stress adaptations in patients with LVH. PMID- 29797431 TI - Efficacy of non-surgical treatments for androgenetic alopecia: a systematic review and network meta-analysis. AB - Androgenetic alopecia, or male/female pattern baldness, is the most common type of progressive hair loss disorder. The aim of this study was to review recent advances in non-surgical treatments for androgenetic alopecia and identify the most effective treatments. A network meta-analysis (NMA) was conducted of the available literature of the six most common non-surgical treatment options for treating androgenetic alopecia in both men and women; dutasteride 0.5 mg, finasteride 1 mg, low-level laser therapy (LLLT), minoxidil 2%, minoxidil 5% and platelet-rich plasma (PRP). Seventy-eight studies met the inclusion criteria, and 22 studies had the data necessary for a network meta-analysis. Relative effects show LLLT as the superior treatment. Relative effects show PRP, finasteride 1 mg (male), finasteride 1 mg (female), minoxidil 5%, minoxidil 2% and dutasteride (male) are approximately equivalent in mean change hair count following treatment. Minoxidil 5% and minoxidil 2% reported the most drug-related adverse events (n = 45 and n = 23, respectively). The quality of evidence of minoxidil 2% vs. minoxidil 5% was high; minoxidil 5% vs. placebo was moderate; dutasteride (male) vs. placebo, finasteride (female) vs. placebo, minoxidil 2% vs. placebo and minoxidil 5% vs. LLLT was low; and finasteride (male) vs. placebo, LLLT vs. sham, PRP vs. placebo and finasteride vs. minoxidil 2% was very low. Results of this NMA indicate the emergence of novel, non-hormonal therapies as effective treatments for hair loss; however, the quality of evidence is generally low. High quality randomized controlled trials and head-to-head trials are required to support these findings and aid in the development of more standardized protocols, particularly for PRP. Regardless, this analysis may aid physicians in clinical decision-making and highlight the variety of non-surgical hair restoration options for patients. PMID- 29797432 TI - Comparative genomic analysis of Myroides odoratimimus isolates. AB - Myroides odoratimimus is an important nosocomial pathogen. Management of M. odoratimimus infection is difficult owing to the multidrug resistance and the unknown pathogenesis mechanisms. Based on our previous genomic sequencing data of M. odoratimimus PR63039 (isolated from a patient with the urinary tract infection), in this study, we further performed comparative genomic analysis for 10 selected Myroides strains. Our results showed that these Myroides genome contexts were very similar and phylogenetically related. Various prophages were identified in the four clinical isolate genomes, which possibly contributed to the genome evolution among the Myroides strains. CRISPR elements were only detected in the two clinical (PR63039 and CCUG10230) isolates and two environmental (CCUG12700 and H1bi) strains. With more stringent cutoff parameters in CARD analysis, the four clinical M. odoratimimus contained roughly equal antibiotic resistance genes, indicating their similar antibiotic resistance profiles. The three clinical (CCUG10230, CCUG12901, CIP101113) and three environmental (CCUG12700, L41, H1bi) M. odoratimimus strains were speculated to carry the indistinguishable virulent factors (VFs), which may involve in the similar pathogenesis mechanism. Moreover, some VFs might confer to the high capacity of dissemination, attacking tissue cells and induction of autoimmune complications. Our results facilitate the research of antibiotic resistance and the development of therapeutic regimens for the M. odoratimimus infections. PMID- 29797433 TI - Experimental Evidence of Chiral Ferrimagnetism in Amorphous GdCo Films. AB - Inversion symmetry breaking has become a vital research area in modern magnetism with phenomena including the Rashba effect, spin Hall effect, and the Dzyaloshinskii-Moriya interaction (DMI)-a vector spin exchange. The latter one may stabilize chiral spin textures with topologically nontrivial properties, such as Skyrmions. So far, chiral spin textures have mainly been studied in helimagnets and thin ferromagnets with heavy-element capping. Here, the concept of chirality driven by interfacial DMI is generalized to complex multicomponent systems and demonstrated on the example of chiral ferrimagnetism in amorphous GdCo films. Utilizing Lorentz microscopy and X-ray magnetic circular dichroism spectroscopy, and tailoring thickness, capping, and rare-earth composition, reveal that 2 nm thick GdCo films preserve ferrimagnetism and stabilize chiral domain walls. The type of chiral domain walls depends on the rare-earth composition/saturation magnetization, enabling a possible temperature control of the intrinsic properties of ferrimagnetic domain walls. PMID- 29797434 TI - Exploring the inhibition mechanism on HIF-2 by inhibitor PT2399 and 0X3 using molecular dynamics simulations. AB - Targeting transcription factors HIF-2 is currently considered to be the most direct way for the therapy of clear cell renal cell carcinoma. The preclinical inhibitor PT2399 and artificial inhibitor 0X3 have been identified as promising on-target inhibitors to inhibit the heterodimerization of HIF-2. However, the inhibition mechanism of PT2399 and 0X3 on HIF-2 remains unclear. To this end, molecular dynamics (MD) simulations and molecular docking were applied to investigate the effects of 2 inhibitors on structural motifs and heterodimerization of HIF-2. Our simulation results reveal that the binding of inhibitors disrupts the crucial hydrogen bond and hydrophobic interactions of interdomain of HIF-2 heterodimer due to the local conformational changes of binding interface, confirming the hypothesis that the perturbation of few residues is sufficient to disrupt the heterodimerization of HIF-2. In addition, it can be found that PT2399 with dominant substituents (cyano, fluorine, sulfuryl, and hydroxyl) is more preferred than 0X3 as HIF-2 inhibitor and these substituents play a crucial role in involving more hydrogen bond interactions with residues of interface and then cause the larger structural change of protein. This study may provide a deeper atomic-level insight into the effect of on-target inhibitors on HIF-2 heterodimer, which is expected to contribute to further rational design of effective clear cell renal cell carcinoma drugs. PMID- 29797435 TI - Low-Temperature Growth of All-Carbon Graphdiyne on a Silicon Anode for High Performance Lithium-Ion Batteries. AB - In situ weaving an all-carbon graphdiyne coat on a silicon anode is scalably realized under ultralow temperature (25 degrees C). This economical strategy not only constructs 3D all-carbon mechanical and conductive networks with reasonable voids for the silicon anode at one time but also simultaneously forms a robust interfacial contact among the electrode components. The intractable problems of the disintegrations in the mechanical and conductive networks and the interfacial contact caused by repeated volume variations during cycling are effectively restrained. The as-prepared electrode demostrates the advantages of silicon regarding capacity (4122 mA h g-1 at 0.2 A g-1 ) with robust capacity retention (1503 mA h g-1 ) after 1450 cycles at 2 A g-1 , and a commercial-level areal capacity up to 4.72 mA h cm-2 can be readily approached. Furthermore, this method shows great promises in solving the key problems in other high-energy-density anodes. PMID- 29797436 TI - Effects of different periodontal treatments in changing the prevalence and levels of Archaea present in the subgingival biofilm of subjects with periodontitis: A secondary analysis from a randomized controlled clinical trial. AB - OBJECTIVE: The aim of this randomized double-blind and placebo-controlled study was to assess if periodontal treatment with or without systemic antibiotic would change the mean level of Archaea. METHODS: Fifty-nine (59) subjects were randomly assigned to receive scaling and root planing (SRP) alone or combined with metronidazole (MTZ; 400 mg/TID) or either with MTZ and amoxicillin (AMX; 500 mg/TID) for 14 days. Clinical and microbiological examinations were performed at baseline and at 6 months post-SRP. Six subgingival plaque samples per subject were analysed for the presence and levels of Archaea using quantitative polymerase chain reaction. RESULTS: Scaling and root planing alone or combined with MTZ or MTZ + AMX significantly reduced the prevalence of subjects colonized by Archaea at 6 months post-therapy, without significant differences among groups (P > .05). Both therapies led to a statistically significant decrease in the mean percentage of sites colonized by Archaea (P < .05). The MTZ and MTZ + AMX group had a significantly lower mean number of sites colonized by Archaea and lower levels of these micro-organisms at sites with probing depth >=5 mm at 6 months compared with SRP group (P < .05). CONCLUSION: Periodontal treatments including adjunctive MTZ or MTZ + AMX are more effective than mechanical treatment alone in reducing the levels and prevalence of sites colonized by Archaea in subjects with chronic periodontitis. PMID- 29797437 TI - Bullous pemphigoid complicated by necrotising fasciitis successfully treated with systemic corticosteroids and antibiotics in combination with i.v. immunoglobulin. PMID- 29797438 TI - Effect of endocannabinoid signalling on cell fate: life, death, differentiation and proliferation of brain cells. AB - Cell fate events are regulated by different endogenous developmental factors such as the cell micro-environment, external or remote signals and epigenetic factors. Among the many regulatory factors, endocannabinoid-associated signalling pathways are known to conduct several of these events in the developing nervous system and in the adult brain. Interestingly, endocannabinoids exert modulatory actions in both physiological and pathological conditions. Endocannabinoid signalling can promote cell survival by acting on non-transformed brain cells (neurons, astrocytes or oligodendrocytes) and can have either a protumoural or antitumoural effect on transformed cells. Moreover, endocannabinoids are able to attenuate the detrimental effects on neurogenesis and neuroinflammation associated with ageing. Thus, the endocannabinoid system emerges as an important regulator of cell fate, controlling cell survival/cell death decisions depending on the cell type and its environment. PMID- 29797439 TI - MP2RAGE and Susceptibility-Weighted Imaging in Lesional Epilepsy at 7T. AB - BACKGROUND AND PURPOSE: Surgery is the first choice therapeutic approach in case of drug-resistant epilepsy. Unfortunately, up to 43% of patients referred for presurgical assessment do not have a lesion detectable by routine 3T magnetic resonance imaging (MRI) (MRI-negative), although most of them likely have an underlying epileptogenic lesion. Thus, new MRI modalities with increased sensibility for epileptogenic lesions are required. This paper describes the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) and susceptibility-weighted imaging (SWI) findings at 7T in a series of patients with drug-resistant epilepsy of different etiologies. METHODS: Prospective pilot study of 7 patients with drug-resistant lesional epilepsy and absence of contraindications for MRI underwent a research 7T head-only scanner. Qualitative analysis of the high-resolution MP2RAGE and SWI sequences is given for each case. This study was approved by the local ethics committee. Written informed consent was obtained from each participant. RESULTS: This study shows that such sequences at ultra-high field are new and valuable approaches to unravel and characterize epileptogenic lesions. Particularly, MP2RAGE shows a better delineation of lesions due to high gray-white matter contrast and structural resolution, and SWI reveals new imaging signs related to improved magnitude and phase contrast imaging. CONCLUSION: MRI at ultra-high field is very promising for the detection of inconspicuous epileptogenic lesions and may facilitate epilepsy surgery of a great number of to-date MRI-negative patients. PMID- 29797440 TI - Paraneoplastic pemphigus in Russian patients: a single center case series. PMID- 29797441 TI - High resolution manometry catheter, test retest reliability and the working mechanism of urethral bulking? PMID- 29797442 TI - Stomach herniation prior to nonreassuring fetal status in a case of fetal gastroschisis. AB - The neonatal prognosis in gastroschisis is generally good; however, intrauterine fetal death (IUFD) and nonreassuring fetal status (NRFS) sometimes occur in fetal cases of gastroschisis. Previously, we reported stomach herniation as a possible risk factor for IUFD or NRFS in fetuses with gastroschisis. We report a case of fetal gastroschisis showing stomach herniation and increased velocity of the umbilical venous (UV) flow the day before NRFS by electronic fetal monitoring (EFM). A 27-year-old pregnant woman was followed up from 16 weeks' gestation due to fetal gastroschisis. At 33 + 1 weeks' gestation, EFM displayed a reassuring fetal state, while the ultrasound examination revealed fetal stomach herniation and an increased flow velocity of the UV in the abdomen. One day later, EFM displayed NRFS, and the patient underwent emergency caesarean section. This case showed stomach herniation preceding the occurrence of NRFS. Stomach herniation may be a predictor of NRFS in fetuses with gastroschisis. PMID- 29797444 TI - Evaluation of beta-carotene assimilation in leopard geckos (Eublepharis macularius). AB - Although leopard geckos (Eublepharis macularius) are commonly kept under human care, their vitamin requirements are largely unknown. Many invertebrate preys display a low vitamin A concentration; thus, gut-loading insects with vitamin A or carotenoids is a common practice. The objective of this prospective experimental study was to investigate whether dietary supplementation with beta carotene, including prey gut-loading, leads to sufficient vitamin A hepatic storage and prevents epithelial squamous metaplasia development in leopard geckos. Ten clinically healthy female leopard geckos were randomly divided in two groups with various supplementations: a group receiving vitamin A supplementation and a group receiving beta-carotene. Insects were gut-loaded continuously with a supplement containing vitamin A or beta-carotene, depending on the group. Oral supplementation with cod liver oil or carrot juice was administered weekly to each lizard from "vitamin A group" and "carotenoid group" respectively. After 10 weeks of supplementation, surgical hepatic biopsies were obtained in three geckos of each group while the two remaining geckos were euthanized to undergo complete necropsy. Hepatic vitamin A concentration was determined for each lizard (n = 10) by ultra-performance liquid chromatography. Histopathology revealed hepatocellular vacuolization and vitellogenic follicles in five females. Epithelial squamous metaplasia was not observed in any of the geckos. Hepatic vitamin A concentration was significantly higher in the carotenoid-supplemented group than in the vitamin A-supplemented group (p = 0.03). Our results suggest that in leopard geckos, dietary supplementation with beta-carotene allows sufficient vitamin A hepatic storage. PMID- 29797446 TI - Immune cell trafficking, lymphatics and hypertension. AB - Activated immune cell infiltration into organs contributes to the development and maintenance of hypertension. Studies targeting specific immune cell populations or reducing their inflammatory signalling have demonstrated a reduction in BP. Lymphatic vessels play a key role in immune cell trafficking and in resolving inflammation, but little is known about their role in hypertension. Studies from our laboratory and others suggest that inflammation-associated or induction of lymphangiogenesis is organ protective and anti-hypertensive. This review provides the basis for hypertension as a disease of chronic inflammation in various tissues and highlights how renal lymphangiogenesis is a novel regulator of kidney health and BP. PMID- 29797443 TI - Cigarette smoke directly impairs skeletal muscle function through capillary regression and altered myofibre calcium kinetics in mice. AB - KEY POINTS: Cigarette smoke components directly alter muscle fatigue resistance and intracellular muscle fibre Ca2+ handling independent of a change in lung structure. Changes in muscle vascular structure are associated with a depletion of satellite cells. Sarcoplasmic reticulum Ca2+ uptake is substantially impaired in myofibres during fatiguing contractions in mice treated with cigarette smoke extract. ABSTRACT: Cigarette smokers exhibit exercise intolerance before a decline in respiratory function. In the present study, the direct effects of cigarette smoke on limb muscle function were tested by comparing cigarette smoke delivered to mice by weekly injections of cigarette smoke extract (CSE), or nose only exposure (CS) 5 days each week, for 8 weeks. Cigarette smoke delivered by either route did not alter pulmonary airspace size. Muscle fatigue measured in situ was 50% lower in the CSE and CS groups than in control. This was accompanied by 34% and 22% decreases in soleus capillary-to-fibre ratio of the CSE and CS groups, respectively, and a trend for fewer skeletal muscle actin-positive arterioles (P = 0.07). In addition, fewer quiescent satellite cells (Nes+Pax7+) were associated with soleus fibres in mice with skeletal myofibre VEGF gene deletion (decreased 47%) and CS exposed (decreased 73%) than with control fibres. Contractile properties of isolated extensor digitorum longus and soleus muscles were impaired. In flexor digitorum brevis myofibres isolated from CSE mice, fatigue resistance was diminished by 43% compared to control and CS myofibres, and this was accompanied by a pronounced slowing in relaxation, an increase in intracellular Ca2+ accumulation, and a slowing in sarcoplasmic reticulum Ca2+ uptake. These data suggest that cigarette smoke components may impair hindlimb muscle vascular structure, fatigue resistance and myofibre calcium handling, and these changes ultimately affect contractile efficiency of locomotor muscles independent of a change in lung function. PMID- 29797445 TI - Hope and mealtime insulin boluses are associated with depressive symptoms and glycemic control in youth with type 1 diabetes mellitus. AB - Adherence to treatment regimen is associated with improved glycemic control and is particularly problematic during adolescence for those with type 1 diabetes mellitus (T1DM). Both glycemic control and adherence may be negatively impacted by poor psychological outcomes in adolescence, such as depressive symptoms and low hopefulness. The purpose of this study was to examine associations between the mealtime insulin bolus score (BOLUS), a more robust proxy measure of adherence than frequency of blood glucose monitoring or self-report, with depressive symptoms, hope, and hemoglobin A1c (HbA1c). Ninety adolescents completed measures of hope (Children's Hope Scale) and depressive symptoms (Center for Epidemiologic Studies-Depression Scale), as well as lab-based measures of HbA1c and mealtime insulin bolus scores (BOLUS). Higher levels of hope were associated with lower levels of depressive symptoms, more frequent mealtime insulin boluses, and better glycemic control. Higher levels of BOLUS behavior were associated with lower depressive symptoms and better glycemic control. Both BOLUS behavior and hope independently and significantly impacted the relationship between depressive symptoms and HbA1c, suggesting a possible mediation. Since hope and BOLUS were each associated with the relationship between depressive symptoms and glycemic control, following confirmation of this relationship in a longitudinal study, clinics may consider measuring hope and BOLUS among youth with high depressive symptoms and further investigating BOLUS behavior and hope as potential intervention targets to improve glycemic control. PMID- 29797447 TI - Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis. AB - PURPOSE: Case reports and pharmacokinetic studies have suggested that concomitant use of low-dose methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low-dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis. METHODS: The study was conducted as a register-based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n = 21 536) and control episodes of use of methotrexate alone (n = 21 725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional-hazards regression, with adjustment using inverse-probability-of-treatment weighting based on propensity scores. RESULTS: During follow-up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person-years) and 129 during control episodes (11.0 per 1000 person-years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07-1.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia. CONCLUSIONS: Concomitant use of low-dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low-dose methotrexate and NSAID are coprescribed. PMID- 29797448 TI - Contemporary trends in the utilisation of radical prostatectomy. PMID- 29797449 TI - Osmotic stress-responsive promoter upstream transcripts (PROMPTs) act as carriers of MYB transcription factors to induce the expression of target genes in Populus simonii. AB - Complex RNA transcription and processing produces a diverse range catalog of long noncoding RNAs (lncRNAs), important biological regulators that have been implicated in osmotic stress responses in plants. Promoter upstream transcript (PROMPT) lncRNAs share some regulatory elements with the promoters of their neighbouring protein-coding genes. However, their function remains unknown. Here, using strand-specific RNA sequencing, we identified 209 differentially regulated osmotic-responsive PROMPTs in poplar (Populus simonii). PROMPTs are transcribed bidirectionally and are more stable than other lncRNAs. Co-expression analysis of PROMPTs and protein-coding genes divided the regulatory network into five independent subnetworks including 27 network modules. Significantly enriched PROMPTs in the network were selected to validate their regulatory roles. We used delaminated layered double hydroxide lactate nanosheets (LDH-lactate-NS) to transport synthetic nucleic acids into live tissues to mimic overexpression and interference of a specific PROMPT. The altered expression of PROMPT_1281 induced the expression of its cis and trans targets, and this interaction was governed by its secondary structure rather than just its primary sequence. Based on this example, we proposed a model that a concentration gradient of PROMPT_1281 is established, which increases the probability of its interaction with targets near its transcription site that shares common motifs. Our results firstly demonstrated that PROMPT_1281 act as carriers of MYB transcription factors to induce the expression of target genes under osmotic stress. In sum, our study identified and validated a set of poplar PROMPTs that likely have regulatory functions in osmotic responses. PMID- 29797450 TI - Prediction of skin anti-aging clinical benefits of an association of ingredients from marine and maritime origins: Ex vivo evaluation using a label-free quantitative proteomic and customized data processing approach. AB - BACKGROUND: The application of ingredients from marine and maritime origins is increasingly common in skin care products, driven by consumer expectations for natural ingredients. However, these ingredients are typically studied for a few isolated in vitro activities. OBJECTIVES: The purpose of this study was to carry out a comprehensive evaluation of the activity on the skin of an association of ingredients from marine and maritime origins using label-free quantitative proteomic analysis, in order to predict the clinical benefits if used in a skin care product. METHODS: An aqueous gel containing 6.1% of ingredients from marine and maritime origins (amino acid-enriched giant kelp extract, trace element enriched seawater, dedifferentiated sea fennel cells) was topically applied on human skin explants. The skin explants' proteome was analyzed in a label-free manner by high-performance liquid nano-chromatography coupled with tandem mass spectrometry. A specific data processing pipeline (CORAVALID) providing an objective and comprehensive interpretation of the statistically relevant biological activities processed the results. RESULTS: Compared to untreated skin explants, 64 proteins were significantly regulated by the gel treatment (q-value <= 0.05). Computer data processing revealed an activity of the ingredients on the epidermis and the dermis. These significantly regulated proteins are involved in gene expression, cell survival and metabolism, inflammatory processes, dermal extracellular matrix synthesis, melanogenesis and keratinocyte proliferation, migration, and differentiation. CONCLUSIONS: These results suggest that the tested ingredients could help to preserve a healthy epidermis and dermis, and possibly to prevent the visible signs of skin aging. PMID- 29797452 TI - A discussion of qualification frameworks, work-readiness and dental education in Australia. PMID- 29797451 TI - Quantitative phosphoproteomics of lectin receptor-like kinase VI.4 dependent abscisic acid response in Arabidopsis thaliana. AB - Lectin receptor-like kinases (LecRKs) play important roles in the responses to adverse environment stress. Abscisic acid (ABA) is a plant hormone involved in plant growth, development and adverse environmental stress responses. Although some studies of ABA response LecRK genes have been reported, the molecular mechanisms of LecRKs regulation of downstream pathways under ABA induction are not well understood. The present study showed that LecRK-VI.4 responded to ABA and negatively regulated stomatal closure. Here, a quantitative phosphoproteomics approach based on mass spectrometry was employed to study the roles of LecRK-VI.4 in the ABA signaling pathway. Metal oxide affinity beads and C18 chromatography were used for phosphopeptide enrichment and separation. The isobaric tags for relative and absolute quantitation were used for profiling the phosphoproteome of mutant lecrk-vi.4-1 and wild-type Col-0 Arabidopsis under normal growth conditions or ABA treatments. In total, 475 unique phosphopeptides were quantified, including 81 phosphopeptides related to LecRK-VI.4 regulation. Gene ontology, protein-protein interaction and motif analysis were performed. The bioinformatics data showed that phosphorylated proteins regulated by LecRK-VI.4 had close relations with factors of stomatal function, which included aquaporin activity, H+ pump activity and the Ca2+ concentration in the cytoplasm. These data have expanded our understanding of how LecRK-VI.4 regulates ABA-mediated stomatal movements. PMID- 29797453 TI - Management of digital eye strain. AB - Digital eye strain, an emerging public health issue, is a condition characterised by visual disturbance and/or ocular discomfort related to the use of digital devices and resulting from a range of stresses on the ocular environment. This review aims to provide an overview of the extensive literature on digital eye strain research with particular reference to the clinical management of symptoms. As many as 90 per cent of digital device users experience symptoms of digital eye strain. Many studies suggest that the following factors are associated with digital eye strain: uncorrected refractive error (including presbyopia), accommodative and vergence anomalies, altered blinking pattern (reduced rate and incomplete blinking), excessive exposure to intense light, closer working distance, and smaller font size. Since a symptom may be caused by one or more factors, a holistic approach should be adopted. The following management strategies have been suggested: (i) appropriate correction of refractive error, including astigmatism and presbyopia; (ii) management of vergence anomalies, with the aim of inducing or leaving a small amount of heterophoria (~1.5Delta Exo); (iii) blinking exercise/training to maintain normal blinking pattern; (iv) use of lubricating eye drops (artificial tears) to help alleviate dry eye-related symptoms; (v) contact lenses with enhanced comfort, particularly at end-of-day and in challenging environments; (vi) prescription of colour filters in all vision correction options, especially blue light-absorbing filters; and (vii) management of accommodative anomalies. Prevention is the main strategy for management of digital eye strain, which involves: (i) ensuring an ergonomic work environment and practice (through patient education and the implementation of ergonomic workplace policies); and (ii) visual examination and eye care to treat visual disorders. Special consideration is needed for people at a high risk of digital eye strain, such as computer workers and contact lens wearers. PMID- 29797454 TI - Use of split-thickness plantar skin grafts in the management of leg and foot skin defects. AB - The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split-thickness skin graft (0.014 in. thick) from a non-weight-bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting. PMID- 29797455 TI - Understanding the geographical burden of stunting in India: A regression decomposition analysis of district-level data from 2015-16. AB - India accounts for approximately one third of the world's total population of stunted preschoolers. Addressing global undernutrition, therefore, requires an understanding of the determinants of stunting across India's diverse states and districts. We created a district-level aggregate data set from the recently released 2015-2016 National and Family Health Survey, which covered 601,509 households in 640 districts. We used mapping and descriptive analyses to understand spatial differences in distribution of stunting. We then used population-weighted regressions to identify stunting determinants and regression based decompositions to explain differences between high- and low-stunting districts across India. Stunting prevalence is high (38.4%) and varies considerably across districts (range: 12.4% to 65.1%), with 239 of the 640 districts have stunting levels above 40% and 202 have prevalence of 30-40%. High stunting districts are heavily clustered in the north and centre of the country. Differences in stunting prevalence between low and high burden districts were explained by differences in women's low body mass index (19% of the difference), education (12%), children's adequate diet (9%), assets (7%), open defecation (7%), age at marriage (7%), antenatal care (6%), and household size (5%). The decomposition models explained 71% of the observed difference in stunting prevalence. Our findings emphasize the variability in stunting across India, reinforce the multifactorial determinants of stunting, and highlight that interdistrict differences in stunting are strongly explained by a multitude of economic, health, hygiene, and demographic factors. A nationwide focus for stunting prevention is required, while addressing critical determinants district by-district to reduce inequalities and prevalence of childhood stunting. PMID- 29797456 TI - Complex regional pain syndrome of the face in a child. PMID- 29797457 TI - Rex in Caldicellulosiruptor bescii: Novel regulon members and its effect on the production of ethanol and overflow metabolites. AB - Rex is a global redox-sensing transcription factor that senses and responds to the intracellular [NADH]/[NAD+ ] ratio to regulate genes for central metabolism, and a variety of metabolic processes in Gram-positive bacteria. We decipher and validate four new members of the Rex regulon in Caldicellulosiruptor bescii; a gene encoding a class V aminotransferase, the HydG FeFe Hydrogenase maturation protein, an oxidoreductase, and a gene encoding a hypothetical protein. Structural genes for the NiFe and FeFe hydrogenases, pyruvate:ferredoxin oxidoreductase, as well as the rex gene itself are also members of this regulon, as has been predicted previously in different organisms. A C. bescii rex deletion strain constructed in an ethanol-producing strain made 54% more ethanol (0.16 mmol/L) than its genetic parent after 36 hr of fermentation, though only under nitrogen limited conditions. Metabolomic interrogation shows this rex-deficient ethanol-producing strain synthesizes other reduced overflow metabolism products likely in response to more reduced intracellular redox conditions and the accumulation of pyruvate. These results suggest ethanol production is strongly dependent on the native intracellular redox state in C. bescii, and highlight the combined promise of using this gene and manipulation of culture conditions to yield strains capable of producing ethanol at higher yields and final titer. PMID- 29797458 TI - Modulation of STAT3 phosphorylation by PTPN2 inhibits naive pluripotency of embryonic stem cells. AB - STAT3 phosphorylation at tyrosine 705 (STAT3pY705 ), triggered by the addition of the leukemia inhibitory factor (LIF), can maintain mouse embryonic stem cell (mESC) self-renewal and reprogram mouse epiblast stem cells (EpiSCs) to enter a naive pluripotent state. The activation of STAT3pY705 occurs mainly through Janus kinases. However, it remains unclear how STAT3pY705 levels are decreased in mESCs. Our study shows that upregulation of the protein tyrosine phosphatase (PTPN2) inhibits STAT3 activity by reducing its phosphorylation level and promotes mESC differentiation, whereas PTPN2 knockout by CRISPR/CAS9 delays mESC differentiation. Consistently, PTPN2 knockdown facilitates the generation of mESC like colonies in STAT3-overexpressing EpiSCs. PTPN2-mediated STAT3 activity, thus, contributes to the exit of ESCs from the pluripotent ground state. These findings expand the current understanding of the regulatory network of naive pluripotency. PMID- 29797459 TI - Mucosal melanoma: clinical and genetic profile. PMID- 29797460 TI - Using CRISPR/Cas9 genome editing in tomato to create a gibberellin-responsive dominant dwarf DELLA allele. AB - The tomato PROCERA gene encodes a DELLA protein, and loss-of-function mutations derepress growth. We used CRISPR/Cas9 and a single guide RNAs (sgRNA) to target mutations to the PROCERA DELLA domain, and recovered several loss-of-function mutations and a dominant dwarf mutation that carries a deletion of one amino acid in the DELLA domain. This is the first report of a dominant dwarf PROCERA allele. This allele retains partial responsiveness to exogenously applied gibberellin. Heterozygotes show an intermediate phenotype at the seedling stage, but adult heterozygotes are as dwarfed as homozygotes. PMID- 29797462 TI - A novel HLA-C variant, HLA-C*04:01:85, detected by next generation sequencing. AB - HLA-C*04:01:85 differs in exon 1 from C*04:01:01 by a single nucleotide substitution in codon 3. PMID- 29797461 TI - Development of Inhalable Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in Microparticulate System for Antituberculosis Drug Delivery. AB - Tuberculosis (TB) is an infectious disease which affects millions of people worldwide. Inhalable polymeric dry powders are promising alternatives as anti-TB drug carriers to the alveoli milieu and infected macrophages, with potential to significantly improve the therapeutics efficiency. Here, the development of a magnetically responsive microparticulate system for pulmonary delivery of an anti TB drug candidate (P3) is reported. Microparticles (MPs) are developed based on a cast method using calcium carbonate sacrificial templates and incorporate superparamagnetic iron oxide nanoparticles to concentrate MPs in alveoli and enable drug on demand release upon actuation of an external alternate magnetic field (AMF). The MPs are shown to be suitable for P3 delivery to the lower airways and for alveolar macrophage phagocytosis. The developed MPs reveal unique and promising features to be used as an inhalable dry powder allowing the AMF control over dosage and frequency of drug delivery anticipating improved TB treatments. PMID- 29797465 TI - Concomitant Acute Toxic Leukoencephalopathy and Posterior Reversible Encephalopathy Syndrome. AB - BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome (PRES) and acute toxic leukoencephalopathy (ATL) are both potentially reversible clinicoradiologic entities. Although their magnetic resonance imaging (MRI) findings differ, rarely both may occur simultaneously in acutely encephalopathic patients. Our aim was to determine the incidence and causes of concomitant "ATL PRES." METHODS: Retrospective search of suspected acutely encephalopathic adults since 1998 throughout our picture archiving and communication system revealed 167 patients with PRES and 106 patients with ATL. Images of these patients were retrospectively evaluated by two neuroradiologists and a fellow to identify the cases which carry both features of PRES and ATL. Imaging findings were scored based on previously reported scoring system as mild, moderate, and severe. The clinical outcome of the patients was determined according to the modified Rankin scale. RESULTS: Our search revealed a series of 6 patients (%2.2) in 273 patients who presented acutely with either encephalopathy or seizures, caused by various etiologies, including immunosuppression following transplantation (n = 2), hypertensive crisis (n = 2), chemotherapy (n = 1), and sepsis (n = 1). MRI demonstrated findings consistent with both PRES and ATL simultaneously on FLAIR and diffusion weighted imaging. Severity of imaging findings of concomitant "ATL PRES" was concordant with each other (rho ~ 1.0, P < .00001), and each patient eventually returned to clinical baseline. This finding, along with their similar etiologies, raises the possibility of an underlying common pathophysiologic thread, perhaps being endothelial toxicity. CONCLUSIONS: Concomitant "ATL-PRES" was found in 2.2% of the patients in a large cohort of ATL and PRES. Etiologies varied. Clinical symptoms and MRI findings were potentially reversible. PMID- 29797463 TI - Japanese scoring systems to predict resistance to intravenous immunoglobulin in Kawasaki disease were unreliable for Caucasian Israeli children. AB - AIM: This study assessed the validity of using established Japanese risk scoring methods to predict intravenous immunoglobulin (IVIG) resistance to Kawasaki disease in Israeli children. METHODS: We reviewed the medical records of 282 patients (70% male) with Kawasaki disease from six Israeli medical centres between 2004 and 2013. Their mean age was 2.5 years. The risk scores were calculated using the Kobayashi, Sano and Egami scoring methods and analysed to determine whether a higher risk score predicted IVIG resistance in this population. Factors that predicted a lack of response to the initial IVIG dose were identified. RESULTS: We found that 18% did not respond to the first IVIG dose. The three scoring methods were unable to reliably predict IVIG resistance, with sensitivities of 23%-32% and specificities of 67%-87%. Calculating a predictive score that was specific for this population was also unsuccessful. The factors that predicted a lacked of response to the first IVIG dose included low albumin, elevated total bilirubin and ethnicity. CONCLUSION: The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children, and we were unable to create a specific scoring method that was able to do this. PMID- 29797466 TI - Strong Coupling of MoS2 Nanosheets and Nitrogen-Doped Graphene for High Performance Pseudocapacitance Lithium Storage. AB - Layered material MoS2 is widely applied as a promising anode for lithium-ion batteries (LIBs). Herein, a scalable and facile dopamine-assisted hydrothermal technique for the preparation of strongly coupled MoS2 nanosheets and nitrogen doped graphene (MoS2 /N-G) composite is developed. In this composite, the interconnected MoS2 nanosheets are well wrapped onto the surface of graphene, forming a unique veil-like architecture. Experimental results indicate that dopamine plays multiple roles in the synthesis: a binding agent to anchor and uniformly disperse MoS2 nanosheets, a morphology promoter, and the precursor for in situ nitrogen doping during the self-polymerization process. Density functional theory calculations further reveal that a strong interaction exists at the interface of MoS2 nanosheets and nitrogen-doped graphene, which facilitates the charge transfer in the hybrid system. When used as the anode for LIBs, the resulting MoS2 /N-G composite electrode exhibits much higher and more stable Li ion storage capacity (e.g., 1102 mAh g-1 at 100 mA g-1 ) than that of MoS2 /G electrode without employing the dopamine linker. Significantly, it is also identified that the thin MoS2 nanosheets display outstanding high-rate capability due to surface-dominated pseudocapacitance contribution. PMID- 29797467 TI - The critical importance of pharyngeal contractile forces on the validity of intrabolus pressure as a predictor of impaired pharyngo-esophageal junction compliance. AB - INTRODUCTION: Restrictive defects of the pharyngo-esophageal junction (PEJ) are common in both structural and neurological disorders and are amenable to therapies aiming to reduce outflow resistance. Intrabolus pressure (IBP) acquired with high-resolution manometry and impedance (HRMI) is an indicator of resistance and a marker of reduced PEJ compliance. Constraints and limitations of IBP as well as the optimal IBP parameter remain undefined. AIMS: To determine: (i) the impact of peak pharyngeal pressure (PeakP) on the diagnostic accuracy of IBP for the detection of a restrictive defect at the PEJ and (ii) the optimal IBP parameter for this purpose. METHODS: In 52 dysphagic patients previously treated for head and neck cancer. Five candidate IBP measures and PeakP were obtained with HRMI, as well as a presence of a stricture determined by a mucosal tear after endoscopic dilatation. Predictive values of IBP measures were evaluated by receiver operating characteristic (ROC) analysis for all patients and reiterated as patients with lowest PeakP were progressively removed from the cohort. RESULTS: All IBP parameters had fair to good accuracy at predicting strictures. Intrabolus pressure measured at a discrete point of maximum admittance 1 cm above the maximal excursion of the upper esophageal sphincter had highest sensitivity (0.76) and specificity (0.78). When PeakP was at least 57 mm Hg both sensitivity and specificity improved to 0.9. CONCLUSIONS: Pharyngeal propulsive force has substantial impact on the accuracy of IBP as a predictor of a PEJ stricture. When PeakP is >=57 mm Hg, an elevated IBP is highly predictive of a restrictive defect at the PEJ. PMID- 29797468 TI - A New Approach to Sustainability: A Moore's Law for Chemistry. AB - "... How do we have a major impact on delivering sustainable chemistry? Carbon neutral laboratories can drive down the environmental costs of chemistry. We propose that sustainable chemistry requires some overarching goal that can be embraced by everyone in the chemical supply chain as well as by the public ..." Read more in the Guest Editorial by Martyn Poliakoff, Peter Licence, and Michael W. George. PMID- 29797469 TI - Sexual behaviour is impaired by the abused inhalant toluene in adolescent male rats. AB - Inhalant misuse is a worldwide problem, especially among adolescents. Toluene is the most widely misused inhalant. One hallmark of adolescence is the emergence of sexual behaviour, which can be affected by drug use. The aim of this study was to analyse the effects of toluene inhalation on different aspects of male rats' sexual behaviour using a binge pattern of exposure in adolescent rats. Male Wistar rats were individually exposed to air or 6,000 ppm toluene for 30 min (acute exposure; n = 8 each) or twice a day for 12 days (repeated exposure; n = 9 each) in static exposure chambers. Independent groups of sexually experienced, adolescent rats (postnatal day 63, PN63) were tested after acute toluene exposure for copulation, sexual incentive motivation or noncontact erections. Sexually naive, adolescent rats (PN45-59) were repeatedly exposed to toluene and tested for sexual behaviour after completing the 1st, 3rd, 5th, 7th, 9th, 11th and 13th exposure sessions. Acute toluene exposure impaired copulatory performance, diminished sexual incentive motivation and delayed noncontact erection occurrence in sexually experienced rats. Repeated toluene exposure during adolescence completely inhibited the onset of copulatory behaviours in sexually naive rats, at the time at which they should have appeared. However, once the inhalant exposure ended, copulatory responses appeared gradually, and animals attained a typical, stable copulatory pattern. In conclusion, acute toluene exposure impairs sexual behaviour in young, sexually experienced animals, while repeated toluene exposure during adolescence prevents the onset of copulatory behaviour, although this effect is transitory. PMID- 29797471 TI - A Reversible Fluorescent Probe for Real-Time Live-Cell Imaging and Quantification of Endogenous Hydropolysulfides. AB - The chemical biology of reactive sulfur species, including hydropolysulfides, has been a subject undergoing intense study in recent years, but further understanding of their "intact" function in living cells has been limited owing to a lack of appropriate analytical tools. In order to overcome this limitation, we developed a new type of fluorescent probe that reversibly and selectively reacts to hydropolysulfides. The probe enables live-cell visualization and quantification of endogenous hydropolysulfides without interference from intrinsic thiol species such as glutathione. Additionally, real-time reversible monitoring of oxidative-stress-induced fluctuation of intrinsic hydropolysulfides has been achieved with a temporal resolution on the order of seconds, a result which has not yet been realized using conventional methods. These results reveal the probe's versatility as a new fluorescence imaging tool to understand the function of intracellular hydropolysulfides. PMID- 29797470 TI - Easy-to-use algorithm would provide faster diagnoses for mucopolysaccharidosis type I and enable patients to receive earlier treatment. AB - AIM: The aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I). METHODS: An international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real-world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested. RESULTS: An algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler-Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) - 16 Hurler, nine Hurler-Scheie and seven Scheie patients - would have been referred earlier if the algorithm had been used. CONCLUSION: The expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment. PMID- 29797472 TI - Impacting incidence of disease through population-based interventions: Appraisal of the ARIC study findings. PMID- 29797473 TI - The categorisation of resistance: interpreting failure to follow a proposed line of action in the diagnosis of autism amongst young adults. AB - Many characteristics typical of autism, a neurodevelopmental condition characterised by socio-communicative impairments, are most evident during social interaction. Accordingly, procedures such as the Autism Diagnosis Observation Schedule (ADOS) are interactive and intended to elicit interactional impairments: a diagnosis of autism is given if interactional difficulties are attributed as a persistent quality of the individual undergoing diagnosis. This task is difficult, first, because behaviours can be interpreted in various ways and, second, because conversation breakdown may indicate a disengagement with, or resistance to, a line of conversation. Drawing upon conversation analysis, we examine seven ADOS diagnosis sessions and ask how diagnosticians distinguish between interactional resistance as, on the one hand, a diagnostic indicator and, on the other, as a reasonable choice from a range of possible responses. We find evidence of various forms of resistance during ADOS sessions, but it is a resistance to a line of conversational action that is often determined to be indicative of autism. However, and as we show, this attribution of resistance can be ambiguous. We conclude by arguing for reflexive practice during any diagnosis where talk is the problem, and for a commitment to acknowledge the potential impact of diagnostic procedures themselves upon results. PMID- 29797474 TI - Optogenetic activation of the central amygdala generates addiction-like preference for reward. AB - Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (~20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences. PMID- 29797477 TI - New Members and Foreign Associates of the National Academy of Sciences. PMID- 29797476 TI - Molecular and physiological characterization of six-way resistance in an Amaranthus tuberculatus var. rudis biotype from Missouri. AB - BACKGROUND: Previous research reported the first case of six-way herbicide resistance in a common waterhemp (Amaranthus tuberculatus var. rudis) biotype from Missouri, USA designated MO-Ren. This study investigated the mechanisms of multiple-resistance in the MO-Ren biotype to herbicides from six site-of-action (SOA) groups, i.e. synthetic auxins, 5-enolypyruvyl-shikimate-3-phosphate synthase (EPSPS)-, protoporphyrinogen oxidase (PPO)-, acetolactate synthase (ALS) , photosystem II (PSII)-, and 4-hydroxyphenyl-pyruvate-dioxygenase (HPPD) inhibitors. RESULTS: Genomic DNA sequencing confirmed the presence of known mutations associated with ALS- or PPO-inhibiting herbicide resistance: the Trp 574-Leu amino acid substitution in the ALS enzyme and the codon deletion corresponding to the DeltaG210 in the PPX2 enzyme. No target-site point mutations associated with resistance to PSII- and EPSPS-inhibitors were detected. Quantitative polymerase chain reaction (qPCR) indicated that MO-Ren plants contained five-fold more copies of the EPSPS gene than susceptible plants. Malathion in combination with 2,4-D (2,4-dichlorophenoxyacetic acid), mesotrione, and chlorimuron POST enhanced the activity of these herbicides indicating that metabolism due to cytochrome P450 monooxygenase activity was involved in herbicide resistance. 4-Chloro-7-nitrobenzofurazan (NBD-Cl), a glutathione-S transferase (GST)-inhibitor, in combination with atrazine did not reduce the biomass accumulation. Reduced absorption or translocation of 2,4-D did not contribute to resistance. However, the resistant biotype metabolized 2,4-D, seven to nine-fold faster than the susceptible. CONCLUSION: Target-site point mutations, gene amplification, and elevated rates of metabolism contribute to six way resistance in the MO-Ren biotype, suggesting both target site and non-target site mechanisms contribute to multiple herbicide resistance in this Amaranthus tuberculatus biotype. (c) 2018 Society of Chemical Industry. PMID- 29797475 TI - Clinical value of jointly detection pleural fluid Midkine, pleural fluid adenosine deaminase, and pleural fluid carbohydrate antigen 125 in the identification of nonsmall cell lung cancer-associated malignant pleural effusion. AB - BACKGROUND: Midkine (MK) level has been shown to be elevated in serum of patients with nonsmall cell lung cancer (NSCLC). However, the diagnostic value of MK in pleural effusion in NSCLC has not been well validated and established. METHODS: Samples of NSCLC-associated malignant pleural effusions (MPE) and benign effusions (BPE) were collected. The pleural fluid MK (pMK), pleural fluid adenosine deaminase (pADA), pleural fluid lactate dehydrogenase (pLDH), pleural fluid glucose (pGLU), pleural fluid ferritin (pFER), pleural fluid CA199 (pCA199), pleural fluid CA125 (pCA125), pleural effusion white cell count (pWBC), and pleural effusion red cell count (pRBC) were analyzed, and the clinical data of each group were collected for statistical analysis. RESULT: The level of pMK, pCA125, pMK + pCA125, and pMK + pCA125 + pADA in the MPE was significantly higher than the BPE group (P = .003, .000, .000, .000). The pADA level in the BPE was significantly higher than the MPE group (P = .003). It showed that the area under the ROC curve (AUC) (0.816) of jointly detection pMK, pCA125, and pADA was significantly higher than other markers for the diagnosis of MPE. Therefore, joint detection of pMK + pCA125 + pADA suggested that the sensitivity, specificity, and AUC was 82.54%, 74.19% at the cutoff 0.47 and diagnostic performance was higher than others. CONCLUSION: Joint detection of pMK + pCA125 + pADA can be used as a good indicator for the identification of MPE of NSCLC. PMID- 29797478 TI - Varicella zoster virus as a possible trigger for the development of pityriasis lichenoides et varioliformis acuta: retrospective analysis of our institutional cases. AB - Although numerous infective agents, including varicella zoster virus (VZV), have been described in association with pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC), none has been identified consistently in these lesions. We sought to immunohistochemically identify VZV glycoprotein (g)E antigens in the vascular endothelium in PLEVA and PLC lesions, based on our previous observation that gE was detected in the vascular endothelium and eccrine unit up until 2 months and 2.5, respectively, years after herpes zoster (HZ) infection. In five of the six cases of PLEVA, VZV gE was identified in the endothelial cells and eccrine epithelium, as observed in HZ lesions, whereas VZV gE was detected in only one of seven patients with PLC. None of the patients with PLEVA who had VZV gE-positive vascular endothelial cells had experienced previous episodes of HZ. VZV may be one of the aetiological agents for PLEVA while other aetiological factors could exist in PLC. PMID- 29797479 TI - Evolutionary divergence of mitochondrial genomes in two Tetranychus species distributed across different climates. AB - There is increasing evidence that mitochondrial genomes (mitogenomes) can be under selection, whereas the selective regimes shaping mitogenome evolution remain largely unclear. To test for mitogenome evolution in relation to the climate adaptation, we explored mtDNA variation in two spider mite (Tetranychus) species that distribute across different climates. We sequenced 26 complete mitogenomes of Tetranychus truncates, which occurs in both warm and cold regions, and nine complete mitogenomes of Tetranychus pueraricola, which is restricted to warm regions. Patterns of evolution in the two species' mitogenomes were compared through a series of dN /dS methods and physicochemical profiles of amino acid replacements. We found that: (1) the mitogenomes of both species were under widespread purifying selection; (2) elevated directional adaptive selection was observed in the T. truncatus mitogenome, perhaps linked to the cold climates adaptation of T. truncatus; and (3) the strength of selection varied across genes, and diversifying positive selection detected on ND4 and ATP6 pointed to their crucial roles during adaptation to different climatic conditions. This study gained insight into the mitogenome evolution in relation to the climate adaptation. PMID- 29797480 TI - A novel psbA mutation (Phe274-Val) confers resistance to PSII herbicides in wild radish (Raphanus raphanistrum). AB - BACKGROUND: Wild radish (Raphanus raphanistrum) is a globally important weed of crops. Two atrazine-resistant wild radish populations (R1 and R2), collected from the Western Australia grain belt, were investigated for resistance to photosystem II (PSII) herbicides. RESULTS: Sequencing of the full-length psbA gene revealed the well-known Ser264-Gly substitution in population R1, whereas population R2 displayed a novel Phe274-Val substitution. Herbicide dose-response studies confirmed that the population with the Ser264-Gly mutation exhibited high-level resistance to atrazine, but super-sensitivity to bromoxynil. Plants possessing the novel Phe274-Val mutation exhibited a modest level of resistance to atrazine, metribuzin and diuron, and were bromoxynil susceptible. Structural modelling of the mutant D1 proteins predicts that the Ser264-Gly mutation endows atrazine resistance by abolishing H-bonds, but confers bromoxynil super-sensitivity by enhancing hydrogen bonding. The Phe274-Val substitution provides resistance to atrazine and diuron by indirectly affecting H-bond formation between the Ser264 residue and the herbicides. CONCLUSION: The results demonstrate that the Phe274 Val mutation is likely responsible for resistance to PSII-inhibiting triazine and urea herbicides. To our knowledge, this is the first evidence of the psbA Phe274 Val mutation in wild radish conferring resistance to PSII herbicides. (c) 2018 Society of Chemical Industry. PMID- 29797481 TI - Refining area of occupancy to address the modifiable areal unit problem in ecology and conservation. AB - The modifiable areal unit problem is prevalent across many aspects of spatial analysis within ecology and conservation. The problem is particularly manifested when calculating metrics for extinction risk estimation, for example, area of occupancy (AOO). Although embedded in the International Union for the Conservation of Nature (IUCN) Red List criteria, AOO is often not used or is poorly applied. We evaluated new and existing methods for calculating AOO from occurrence records and devised a method for determining the minimum AOO with a uniform grid. We evaluated the grid cell shape, origin, and rotation with real world and simulated data and reviewed the effects on AOO values and possible impacts for species already assessed on the IUCN Red List. The AOO varied by up to 80%, and a ratio of cells to points of 1:1.21 yielded the maximum variation in the number of occupied cells. These findings potentially impact 3% of existing species on the IUCN Red List and species not yet assessed. Our new method combined grid rotation and moving grid origin and gave fast, robust, and reproducible results and, in the majority of cases, achieved the minimum AOO. As well as determining minimum AOO, our method yielded a confidence interval that should be incorporated into existing tools that support species risk assessment. We recommend when recording AOO and other areal measurements that the methods; summary statistics across multiple iterations; angle and origin of the minimum grid; map projection; and datum be recorded, this will lead to more robust species risk assessments. PMID- 29797483 TI - Serial passage through resistant and susceptible cucumber cultivars affects the virulence of Fusarium oxysporum f. sp. cucumerinum. AB - Fusarium oxysporum f. sp. cucumerinum (Foc) is the causal pathogen of cucumber Fusarium wilt resulting in losses to cucumber production. To investigate the effects of the selective pressures of host plants on the virulence of Foc, a low virulence isolate, foc-3b, was successively inoculated on resistant and susceptible cucumber cultivars for five generations. The virulence of the original isolate diverged; virulence was significantly strengthened after serial passage on the resistant cultivar and weakened on the susceptible plants (p ? .05). The expression of four virulence-related genes of F. oxysporum, G-protein alpha subunit gene fga1, sucrose nonfermenting 1 gene snf1, F-box protein gene frp1, and Class V chitin synthase gene chsV, was quantified using real-time PCR. All genes were significantly upregulated after serial passage on the resistant cultivar, compared to the original strain, and the expression of snf1 was downregulated in strains re-isolated from the susceptible plants (p ? .05). A significant positive correlation was found between the expression levels of gene snf1, frp1, and chsV and disease severity of cucumber Fusarium wilt, suggesting these genes may impact virulence differentiation. This study will improve the management of cucumber Fusarium wilt and provide insight into the mechanisms underlying virulence of F. oxysporum. PMID- 29797484 TI - Flexibility of pigment cell behavior permits the robustness of skin pattern formation. AB - The striped pigmentation pattern of zebrafish is determined by the interaction between pigment cells with different colors. Recent studies show the behaviors of pigment cells are substantially different according to the environment. Interestingly, the resulting patterns are almost identical, suggesting a robustness of the patterning mechanism. To know how this robustness originates, we investigated the behavior of melanophores in various environments including different developmental stages, different body positions, and different genetic backgrounds. Normally, when embryonic melanophores are excluded from the yellow stripe region in the body trunk, two different cellular behaviors are observed. Melanophores migrate to join the black stripe or disappear (die) in the position. In environments where melanophore migration was restricted, we observed that most melanophores disappeared in their position, resulting in the complete exclusion of melanophores from the yellow stripe. In environments where melanophore cell death was restricted, most melanophores migrated to join the black stripes, also resulting in complete exclusion. When both migration and cell death were restricted, melanophores remained alive in the yellow stripes. These results show that migration and cell death complement each other to achieve the exclusion of melanophores. This flexibility may be the basis of the mechanistic robustness of skin pattern formation. PMID- 29797482 TI - Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface. AB - Orofacial clefting represents the most common craniofacial birth defect. Cleft lip with or without cleft palate (CL/P) is genetically distinct from cleft palate only (CPO). Numerous transcription factors (TFs) regulate normal development of the midface, comprising the premaxilla, maxilla and palatine bones, through control of basic cellular behaviors. Within the Pbx family of genes encoding Three Amino-acid Loop Extension (TALE) homeodomain-containing TFs, we previously established that in the mouse, Pbx1 plays a preeminent role in midfacial morphogenesis, and Pbx2 and Pbx3 execute collaborative functions in domains of coexpression. We also reported that Pbx1 loss from cephalic epithelial domains, on a Pbx2- or Pbx3-deficient background, results in CL/P via disruption of a regulatory network that controls apoptosis at the seam of frontonasal and maxillary process fusion. Conversely, Pbx1 loss in cranial neural crest cell (CNCC)-derived mesenchyme on a Pbx2-deficient background results in CPO, a phenotype not yet characterized. In this study, we provide in-depth analysis of PBX1 and PBX2 protein localization from early stages of midfacial morphogenesis throughout development of the secondary palate. We further establish CNCC specific roles of PBX TFs and describe the developmental abnormalities resulting from their loss in the murine embryonic secondary palate. Additionally, we compare and contrast the phenotypes arising from PBX1 loss in CNCC with those caused by its loss in the epithelium and show that CNCC-specific Pbx1 deletion affects only later secondary palate morphogenesis. Moreover, CNCC mutants exhibit perturbed rostro-caudal organization and broadening of the midfacial complex. Proliferation defects are pronounced in CNCC mutants at gestational day (E)12.5, suggesting altered proliferation of mutant palatal progenitor cells, consistent with roles of PBX factors in maintaining progenitor cell state. Although the craniofacial skeletal abnormalities in CNCC mutants do not result from overt patterning defects, osteogenesis is delayed, underscoring a critical role of PBX factors in CNCC morphogenesis and differentiation. Overall, the characterization of tissue-specific Pbx loss-of-function mouse models with orofacial clefting establishes these strains as unique tools to further dissect the complexities of this congenital craniofacial malformation. This study closely links PBX TALE homeodomain proteins to the variation in maxillary shape and size that occurs in pathological settings and during evolution of midfacial morphology. PMID- 29797485 TI - Genome editing reveals the function of Yorkie during the embryonic and early larval development in silkworm, Bombyx mori. AB - As a transcriptional coactivator, Yorkie (Yki) is a major downstream target of the Hippo signalling pathway to regulate the organ size during animal development and regeneration. Previous microarray analysis in the silkworm, Bombyx mori, has shown that genes associated with the Hippo pathway were primarily expressed in gonads and imaginal discs. The RNA-interference-mediated silencing of Yki at the early wandering stage delayed B. mori development and ovary maturation, whereas baculovirus-mediated overexpression at the late larval instar facilitated organ growth and accelerated metamorphosis. Here, we employed CRISPR/Cas9-mediated mutagenesis to investigate the function of Yki in B. mori (BmYki) at the embryonic and early larval stages. Knocking out of BmYki led to reduced body size, moulting defects and, eventually, larval lethality. Sequence analysis of CRISPR/Cas9 mutants exhibited an array of deletions in BmYki. As a critical downstream effector of the Hippo kinase cassette, silencing of BmYki at the embryonic stage is indispensable and the consequence is lethal. Given that the Hippo signalling pathway is evolutionarily conserved, Yki has the potential to be a novel molecular target for genetic-based pest management practices. PMID- 29797486 TI - Analysis of predictors of pain response in patients with bone metastasis undergoing palliative radiotherapy: Does age matter? AB - INTRODUCTION: To evaluate whether age is a predictor of pain response after radiotherapy for painful bone metastasis (BM). METHODS: Between June 2010 and June 2014, 204 patients with BM undergoing palliative radiotherapy participated in a multicentre prospective study. Patients completed the Brief Pain Inventory (BPI) to rate the intensity pain (from 0 to 10) at baseline and 4 weeks after radiotherapy. To determine which variables predicted pain response and particularly whether age is a predictor, logistic regression analysis was used. Baseline variables considered were: age (<=65/66-75/>75 years), sex, Eastern Cooperative Oncology Group performance status (0-1/>=2), pretreatment pain score (<=4/5-7/>=8), radiotherapy (single/multiple fraction), primary tumour location, visceral metastases (yes/no), concomitant systemic chemotherapy and bisphosphonate use (yes/no). RESULTS: Pain response was assessed in the 128 patients who completed BPI pretreatment and at 4 weeks after radiotherapy. According to univariate analysis, pain response was better in over 75-year-olds than younger patients: (OR, 3.2; 95% CI, 1.1-9.1; P = 0.031). Response was better in patients receiving multiple fractions rather than a single fraction of 8 Gy (OR, 2.8; 95% CI, 1.2-6.1; P = 0.01), and in patients with a pretreatment pain score >=8 vs <=7 (OR, 2.4; 95% CI, 1.1-5.0; P = 0.017). No other variables were significant. Multivariate analysis showed that treatment schedule (OR, 3.4; 95% CI 1.4-7.9; P = 0.004) and pre-radiotherapy pain score (OR, 2.8; 95% CI 1.3-6.3; P = 0.009) were the only independent predictors of pain response. CONCLUSION: All patients with painful bone metastasis should be referred for palliative radiotherapy to relieve the pain regardless of age. Therefore, an older age should not be a reason to withhold palliative radiation treatment. PMID- 29797487 TI - Adsorption of Hydrogen Sulfide, Hydrosulfide and Sulfide at Cu(110) - Polarizability and Cooperativity Effects. First Stages of Formation of a Sulfide Layer. AB - Understanding the surface site preference for single adsorbates, the interactions between adsorbates, how these interactions affect surface site specificity in adsorption and perturb the electronic states of surfaces is important for rationalizing the structure of interfaces and the growth of surface products. Herein, using density functional theory (DFT) calculations, we investigated the adsorption of H2 S, HS and, S onto Cu(110). The surface site specificity observed for single adsorbates can be largely affected by the presence of other adsorbates, especially S that can affect the adsorption of other species even at distances of 13 A. The large supercell employed with a surface periodicity of (6*6) allowed us to safely use the Helmholtz method for the determination of the dipole of the surface-adsorbate complex at low adsorbate coverages. We found that the surface perturbation induced by S can be explained by the charge transfer model, H2 S leads to a perturbation of the surface that arises mostly from Pauli exclusion effects, whereas HS shows a mix of charge transfer and Pauli exclusion effects. These effects have a large contribution to the long range adsorbate adsorbate interactions observed. Further support for the long range adsorbate adsorbate interactions are the values of the adsorption energies of adsorbate pairs that are larger than the sum of the adsorption energies of the single adsorbates that constitute the pair. This happens even for large distances and thus goes beyond the H-bond contribution for the H-bond capable adsorbate pairs. Exploiting this knowledge we investigated two models for describing the first stages of growth of a layer of S-atoms at the surface: the formation of islands versus the formation of more homogeneous surface distributions of S-atoms. We found that for coverages lower than 0.5 ML the S-atoms prefer to cluster as islands that evolve to stripes along the [1 1? 0] direction with increasing coverage. At 0.5 ML a homogeneous distribution of S-atoms becomes more stable than the formation of stripes. For the coverage equivalent to 1 ML, the formation of two half monolayers of S-atoms that disrupt the Cu-Cu bonds between the first and second layer is more favorable than the formation of 1 ML homogeneous coverage of S atoms. Here the S-Cu bond distances and geometries are reminiscent of pyrite, covellite, and to some extent chalcocite. The small energy difference of ~0.1 eV that exists between this structure and the formation of 1 ML suggests that in a real system at finite temperature both structures may coexist leading to a structure with even lower symmetry. PMID- 29797488 TI - Primary prevention of chronic kidney disease through population-based strategies for blood pressure control: The ARIC study. AB - While much of the chronic kidney disease (CKD) literature focuses on the role of blood pressure reduction in delaying CKD progression, little is known about the benefits of modest population-wide decrements in blood pressure on incident CKD. The authors used multivariable linear regression to characterize the impact on incident CKD of two approaches for blood pressure management: (1) a 1-mm Hg reduction in systolic BP across the entire study population; and (2) a 10% reduction in participants with unaware, untreated, and uncontrolled BP above goal as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) thresholds. Over a mean of 20 years of follow-up (ARIC [Atherosclerosis Risk in Communities] study, n = 15 390), 3852 incident CKD events were ascertained. After adjustment, a 1-mm Hg decrement in systolic BP across the population was associated with an estimated 11.7 (95% confidence interval [CI], 6.2-17.3) and 13.4 (95% CI, 10.3 16.6) fewer CKD events per 100 000 person-years in blacks and whites, respectively. Among participants with BP above JNC 7 goal, a 10% decrease in unaware, untreated, or uncontrolled BP was associated with 3.2 (95% CI, 2.0-4.9), 2.8 (95% CI, 1.8-4.3), and 5.8 (95% CI, 3.6-8.8) fewer CKD events per 100 000 person-years in blacks and 3.1 (95% CI, 2.3-4.1), 0.7 (95% CI, 0.5-0.9), and 1.0 (95% CI, 1.3-2.4) fewer CKD events per 100 000 person-years in whites. Modest population-wide reductions in systolic BP hold potential for the primary prevention of CKD. PMID- 29797489 TI - Novel autosomal recessive LAMA3 and PLEC variants underlie junctional epidermolysis bullosa generalized intermediate and epidermolysis bullosa simplex with muscular dystrophy in two consanguineous families. PMID- 29797490 TI - Congenital acute myeloid leukaemia with KMT2A rearrangement. PMID- 29797491 TI - The effectiveness of a nail-biting prevention program among primary school students. AB - PURPOSE: This study aimed to demonstrate the effect of a program called "Do Not Bite Your Nails, Cut Your Nails," which is based on a health promotion model to change the nail-biting habit among primary school students. DESIGN AND METHODS: This quasi-experimental study was conducted using the pre- and post-test and interrupted time series design. The study sample included 299 students. Nurse observation form and nail follow-up chart were used to evaluate behavioral outcomes. This program was conducted under the guidance of school nurses and lasted 6 weeks. The data were analyzed using McNemar and Cochran Q tests. RESULTS: The number of those who selected "yes" for "I cut my nails this weekend" and "I didn't bite my nails today" increased. However, the number of the students that selected "yes" for "I pulled out my nails," "I pulled out and ate," "I pulled out my nail skin," "My cuticle bled today," and "My nails hurt today" decreased significantly and statistically compared with pretest, first and second observation, and post-test (P < 0.001). The rate of the students with minimum one abnormal finger was 83.9% according to observations, and 6% following the intervention (P < 0.001). New insights were provided into the program to diminish nail-biting habit. PRACTICE IMPLICATIONS: The program significantly reduced the nail-biting rate among primary school students. The nurse that implement this program will be able to do a comprehensive evaluation of students' nail-biting habits, perform solution-focused interventions, and prevent advanced complications that might develop in connection to nail-biting. Thus, the effectiveness of nursing implementations will improve in the prevention of nail biting habit, early diagnosis, and changing students' habits. "Do Not Bite Your Nails, Cut Your Nails" program can be applied again in different schools. PMID- 29797492 TI - The regulation of three new members of the cytochrome P450 CYP6 family and their promoters in the cotton aphid Aphis gossypii by plant allelochemicals. AB - BACKGROUND: The expression of P450 genes in insects can be induced by plant allelochemicals. To understand the induction mechanisms, we measured the expression profiles of three P450 genes and their promoter activities under the induction of plant allelochemicals. RESULTS: The inducible expression of CYP6CY19 was the highest among three genes, followed by those of CYP6CY22 and CYP6DA1. The regions from -687 to +586 bp of CYP6DA1, from -666 to +140 bp of CYP6CY19 and from -530 to +218 bp of CYP6CY22 were essential for basal transcriptional activity. The cis-elements for plant allelochemicals induction were identified between -193 and +56 bp of CYP6DA1, between -157 and +140 bp of CYP6CY19 and between -108 and +218 bp of CYP6CY22. These promoter regions were found to contain a potential aryl hydrocarbon receptor element binding site with a conservative sequence motif 5'-C/TAC/ANCA/CA-3'. All these four plant allelochemicals were able to induce the expression of these P450 genes. Tannic acid had a better inductive effect than other three plant allelochemicals. CONCLUSIONS: Our study identified the plant allelochemical responsive cis elements. This provides further research targets aimed at understanding the regulatory mechanisms of P450 genes expression and their interactions with plant allelochemicals in insect pests. (c) 2018 Society of Chemical Industry. PMID- 29797493 TI - The integration and application of genomic information in mangrove conservation. PMID- 29797494 TI - Marine macroalgae as sources of protein and bioactive compounds in feed for monogastric animals. AB - Marine macroalgae are considered as promising sustainable alternatives to conventional terrestrial animal feed resources. The advantages include high growth rate, potential cultivation in saltwater, and no occupation of arable land. Macroalgae are broadly classified as brown (Phaeophyta), red (Rhodophyta) and green (Chlorophyta) algae, and are a diverse group of marine organisms. The nutritional value of macroalgae is highly variable. The protein and essential amino acid content can be low, especially in brown species, and indigestible polysaccharides adversely affect the energy value. Optimal use of macroalgae in feeds requires suitable processing, and biorefinery approaches may increase protein content and improve nutrient availability. Macroalgae are rich in unique bioactive components and there is a growing interest in the potentially beneficial health effects of compounds such as laminarin and fucoidan in different macroalgal and macroalgal products. This review summarizes current literature on different aspects of the use of macroalgae as sources of protein and health-promoting bioactive compounds in feed for monogastric animal species. (c) 2018 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID- 29797495 TI - Enantioselective Alkylation of N-Arylhydrazones Derived from alpha-Keto Esters and Isatin Derivatives through Asymmetric Phase-Transfer Catalysis. AB - The phase-transfer-catalyzed asymmetric alkylation reactions of N-arylhydrazones derived from alpha-keto-esters and isatin derivatives afford enantioenriched azo compounds that bear a tetra-substituted carbon stereocenter in good yields with high chemo- and enantioselectivity. The alkylation products can be readily converted into chiral amino esters, hydrazine derivatives, and aza-beta-lactams without loss of enantiopurity. PMID- 29797496 TI - Polypharmacological Drug-target Inference for Chemogenomics. AB - Pharmacological drug actions are often caused by multi-target effects. While most of the currently approved synthetic drugs were designed to interact with a single 'on-target', these chemical agents often interact with additional 'off-targets'. Understanding and rationalizing these multiple interactions will be indispensable for the design of future precision medicines. We employed computational predictions of drug-target interactions to analyze functional drug-drug relationships. 900 approved drugs were represented in terms of their predicted activity fingerprints, considering 1158 potential target activities. A drug relationship network was constructed based on fingerprint similarity. The resulting network graph highlights clusters of compounds sharing similar predicted on- and off-targets, and allows to identify mutual targets of drugs that were originally developed for different therapeutic indications. Such an analysis offers straightforward access to spotting potential off-target liabilities and drug-drug interactions, as well as drug repurposing opportunities. PMID- 29797497 TI - Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB-related skeletal disorders in three fetuses and a 106-year-old exhibit. AB - The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. These characteristics allowed the diagnosis of Piepkorn type of osteochondrodysplasia in four new cases, three fetuses of 15 to 22 weeks and one 106-year-old museum exhibit. Piepkorn type of osteochondrodysplasia has been assigned to the giant cell chondrodysplasias such as atelosteogenesis type 1 (AO1) and boomerang dysplasia (BD). Analysis of the Filamin B gene in 3p14.3, which is associated with these disorders, allowed the identification of the first FLNB mutations in Piepkorn type of osteochondrodysplasia. The heterozygous missense mutations, found in the three fetuses, were located in exons 28 and 29, encoding the immunoglobulin-like repeat region R15, one of three mutational hot spots in dominant FLNB-related skeletal disorders. Direct preparations and alcian blue staining revealed single upper and lower arm and leg bone primordia, preaxial oligodactyly, and polysyndactyly with complete fusion and doubling of the middle and end phalanges II-V to produce eight distal finger rays. Considering the unique clinical features and the extent of underossification, Piepkorn type of osteochondrodysplasia can be regarded as a distinct entity within the AO1-BD-POCD continuum. PMID- 29797498 TI - Challenging behaviours at early adulthood in autism spectrum disorders: topography, risk factors and evolution. AB - BACKGROUND: Challenging behaviours are highly prevalent in children and adolescents with autism spectrum disorders (ASD), but little is known about the prevalence and course of these behaviours during adulthood. The aims of this study were to describe the topography of challenging behaviours in a cohort of 106 young adults with ASD and to identify the risk factors for challenging behaviours. Our secondary objective was to study the changes in challenging behaviours from adolescence to early adult years. METHOD: The present study uses data from the EpiTED prospective follow-up study in France. The presence of challenging behaviours was assessed by the Aberrant Behaviour Checklist (ABC) completed by parent informants. Several dimensions of behaviour were studied: irritability, stereotypy, lethargy, hyperactivity and self-injury. Clinical variables were collected on ASD symptom severity, cognitive and language levels, adaptive behaviours and comorbid medical disorders. RESULTS: The presence of challenging behaviours at early adulthood was related to the young adult's cognitive and language level, ASD symptom severity and comorbid gastrointestinal and sleep disorders. The main risk factor for challenging behaviours was ASD symptom severity. The level of language impairment was a significant predictor of self-injury. Gastrointestinal disorders were a significant predictor of stereotypy. The change in behaviour topography from adolescence to early adult years corresponded with decreased parent report of hyperactivity, but no significant decrease in parent reports of irritability, stereotypy, lethargy and self-injurious behaviours. CONCLUSIONS: The challenging behaviours in individuals with ASD persist in early adulthood and are related to core symptom severity, levels of cognitive and language impairments and medical comorbidity. The results emphasise the importance of early interventions for children with ASD to target cognitive and language abilities and to alleviate the severity of ASD symptoms. They also underscore the need to enhance opportunities for individuals with ASD to better communicate discomforts and pain in the context of medical illness. PMID- 29797499 TI - Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment. AB - BACKGROUND: Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. METHODS: Thirty four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. RESULTS: Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade >=III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade >=III had a better prognosis than those with Evans grade 1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC). RESULTS: Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 +/- 38.3 vs. 777.5 +/- 39.9 mmol * min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of +/ 20%. CONCLUSION: Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements. PMID- 29797505 TI - Fetal lung size after thoracoamniotic shunting reflects survival in primary fetal hydrothorax with hydrops. AB - AIM: To assess the role of lung size and abnormal Doppler findings in the umbilical artery (UA) in determining the outcomes of fetuses with primary fetal hydrothorax (FHT) associated with hydrops who underwent thoracoamniotic shunting (TAS). METHODS: This was a retrospective study at a single center. We included cases of primary FHT with hydrops who underwent TAS at our hospital between 2004 and 2016. We assessed the relationship between mortality until 28 days after birth and ultrasound findings, including absent or reversed end-diastolic velocity (AREDV) in the UA and the lung-to-thorax transverse area ratio (LTR), before and after TAS. RESULTS: Forty-one cases of primary FHT with hydrops underwent TAS. The median (range) gestational age at TAS was 28.5 (19.3-33.8) weeks. Bilateral pleural effusion was observed in 39 cases (95.1%). Among the 41 cases, 19 (46.4%) survived, 11 (26.8%) died in utero, and 11 (26.8%) died in the neonatal period. AREDV in the UA before and after TAS were not associated with mortality (P = 0.32 and 0.47, respectively). The odds ratio for mortality in LTR 0.2-0.3 before TAS was 0.62 (vs LTR < 0.2, P = 0.45) and that in LTR 0.2-0.3 and > 0.3 after TAS were 0.27 and 0.06, respectively (vs LTR < 0.2, P for trend <0.01). CONCLUSION: A larger LTR after TAS was significantly associated with a better prognosis in hydropic primary FHT. The fetal lung size after the procedure may be a prognostic factor of primary FHT. PMID- 29797506 TI - A commentary about the importance of fetal and neonatal soft-tissue assessment. PMID- 29797507 TI - The Ghent Global IAD Monitoring Tool (GLOBIAD-M) to monitor the healing of incontinence-associated dermatitis (IAD): Design and reliability study. AB - The aim of this study was to design and evaluate the reliability of the Ghent Global incontinence-associated dermatitis (IAD) Monitoring Tool (GLOBIAD-M). The tool was designed based on the internationally validated Ghent Global IAD Categorisation Tool (GLOBIAD). After designing and validation by experts, one trained researcher carried out 36 observations of 9 patients affected with IAD. Photographs of the IAD lesions were independently assessed by a second trained researcher. Measures for inter-rater agreement (po ) and reliability [Cohen's Kappa (K) and intra-class correlation coefficients (ICC)] were analysed. The po ranged between 0.86 for the item 'maceration' and 0.97 for the item 'clinical signs of infection'. The K for the item 'GLOBIAD classification' was 0.61 [95% confidence interval (CI) 0.28-0.95] and 0.72 (95% CI 0.50-0.95) for 'maceration'. The lowest K was found for the item 'oedema' (0.27; 95% CI -0.24-0.79). The ICC of the item 'redness' was 0.83 (95% CI 0.69-0.91) and 0.87 (95% CI 0.76-0.93) for 'skin loss'. The inter-rater agreement and reliability of the GLOBIAD-M appears to be good for the assessment of photographs by experts. This tool could support clinical decision-making for IAD treatment. Further validation with clinicians is, however, needed. PMID- 29797508 TI - Synergetic Combinations of Dual-Targeting Ligands for Enhanced In Vitro and In Vivo Tumor Targeting. AB - The concept of dual-ligand targeting has been around for quite some time, but remains controversial due to the intricate interplay between so many different factors such as the choice of dual ligands, their densities, ratios and length matching, etc. Herein, the synthesis of a combinatorial library of single and dual-ligand nanoparticles with systematically varied properties (ligand densities, ligand ratios, and lengths) for tumor targeting is reported. Folic acid (FA) and hyaluronic acid (HA) are used as two model targeting ligands. It is found that the length matching and ligand ratio play critical roles in achieving the synergetic effect of the dual-ligand targeting. When FA is presented on the nanoparticle surface through a 5K polyethylene glycol (PEG) chain, the dual ligand formulations using the HA with either 5K or 10K length do not show any targeting effect, but the right length of HA (7K) with a careful selection of the right ligand ratio do enhance the targeting efficiency and specificity significantly. Further in vitro 3D tumor spheroid models and in vivo xenograft mice models confirm the synergetic targeting efficiency of the optimal dual ligand formulation (5F2H7K ). This work provides a valuable insight into the design of dual-ligand targeting nanosystems. PMID- 29797510 TI - Neisseria meningitidis urethritis: synthesis of published data. PMID- 29797509 TI - PRUNE1-related disorder: Expanding the clinical spectrum. AB - Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Eight mutations have been reported in 13 unrelated families. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. One recurrent missense mutation (p.Asp106Asn) was previously reported in Turkish and Italian families, while the other 2 mutations (p.Leu18Serfs*8 and p.Cys180*) are novel. We also show that mutant PRUNE1 mRNA can be subject to nonsense-mediated mRNA decay. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes. PMID- 29797511 TI - Validated quantitative trait loci for eggshell quality in experimental and commercial laying hens. AB - Compromised eggshell quality causes considerable economic losses for the egg industry. Breeding for improved eggshell quality has been very challenging. Eggshell quality is a trait that would greatly benefit from marker-assisted selection, which would allow the selection of sires for their direct contribution to the trait and would also allow implementation of measurements integrating a number of shell parameters that are difficult to measure. In this study, we selected the most promising autosomal quantitative trait loci (QTL) affecting eggshell quality on chromosomes 2, 3, 6 and 14 from earlier experiments and we extended the F2 population to include 1599 F2 females. The study was repeated on two commercial populations: Lohmann Tierzucht Rhode Island Red line (n = 692 females) and a Hy-Line White Plymouth Rock line (n = 290 progeny tested males). We analyzed the selected autosomal QTL regions on the three populations with SNP markers at 4-13 SNPs/Mb density. QTL for eggshell quality were replicated on all studied regions in the F2 population. New QTL were detected for eggshell color on chromosomes 3 and 6. Marker associations with eggshell quality traits were validated in the tested commercial lines on chromosomes 2, 3 and 6, thus paving the way for marker-assisted selection for improved eggshell quality. PMID- 29797512 TI - Characterization of spectral and intensity changes with measurement geometry in various light guides used in scintillation dosimetry. AB - PURPOSE: To characterize response changes of various light guides used in megavoltage (MV) photon beam scintillation dosimetry as a function of irradiation conditions. Particular emphasis was placed on quantifying the impact of response changes on the Cerenkov light ratio (CLR). METHODS: Intensity and spectral response measurements as a function of dose, depth, and fiber-beam angle were performed with a commercial scintillation detector stripped of its scintillation material and five different custom-made light guides. The core materials of the light guides investigated consisted of polymethyl methacrylate (PMMA), low- and high-hydroxyl content silica, and polystyrene. Dose levels ranging from 50 monitor units (MU) to 1000 MU, depths ranging from 1 to 20 cm, and fiber-beam angles ranging from 10 degrees to 90 degrees were investigated. All measurements were performed at a photon beam energy of 6 MV. The CLR was calculated by taking the ratio of the responses in the blue to green spectral regions. RESULTS: There was no significant change in the CLR measured with the modified commercial scintillation detector as a function of delivered dose. In addition, increases in the CLR as functions of depth and fiber-beam angle were observed where the maximum changes were 4.2% and 3.6%, respectively. The spectrum measurements showed no observable changes in spectral shape with depth except for the low-hydroxyl content silica fiber. Variations in the measured spectral shape with fiber-beam angle were observed for all fibers investigated. The magnitude of the changes in the spectral shape varied with fiber type, where the silica fibers exhibited the largest changes and the plastic fibers exhibited the smallest changes. Increases in the CLR were observed for the silica fibers with depth and for all fibers with fiber-beam angle. The plastic fibers showed no significant change in the CLR as a function of depth. Increases of 3.1% and 9.5% in the CLR were observed for the high- and low-hydroxyl content silica fibers, respectively, over the range of depths investigated. Variations of 2.3%, 6.1%, 5.1% and 11.9% were observed for the PMMA, polystyrene, high-hydroxyl, and low-hydroxyl content silica fiber CLR values as a function of fiber-beam angle, respectively. CONCLUSIONS: The insignificant change in the CLR with delivered dose indicates that a single CLR value over the investigated dose range is sufficient for accurate Cerenkov subtraction. Variations in the stem-effect spectrum shape can occur with changes in irradiation geometry. The magnitude of the changes are governed by the fiber construction and the optical properties of the fiber. The observed spectral shape changes can be explained by a combination of variations in optical path length through the fiber and the fiber fluorescent signal contribution to the stem-effect. These spectral shape variations directly influence the calculated CLR values. This work confirms that careful characterization of scintillation detectors is important as changes in the stem effect spectrum can cause changes in the CLR. If the CLR changes between the reference and measurement conditions, this could result in an incorrect stem effect subtraction and reduced measurement accuracy. PMID- 29797514 TI - Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study. AB - BACKGROUND: Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era. AIM: To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. METHODS: We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity. RESULTS: Among 13 663 persons on SOF/LDV+/-ribavirin, 14% and 1% persons had CKD Stage 3 and 4-5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD+/-ribavirin, 9% and 3% persons had CKD Stage 3 and 4-5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4-5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%-38% of persons with baseline eGFR >=60 mL/min/1.73 m2 , but in only 0%-6% with CKD4-5. Grade 3/4 anaemia was more frequent in persons with CKD4 5, but ribavirin co-administration did not appear to affect this. CONCLUSIONS: SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear. PMID- 29797513 TI - The Development of a Conceptual Framework and Preliminary Item Bank for Childbirth-Specific Patient-Reported Outcome Measures. AB - OBJECTIVE: To develop a conceptual framework and preliminary item bank for childbirth-specific patient-reported outcome (PRO) domains. DATA SOURCES: Women, who were U.S. residents, >=18 years old, and >=20 weeks pregnant, were surveyed regarding their childbirth values and preferences (V&P) using online panels. STUDY DESIGN: Using community-based research techniques and Patient-Reported Outcomes Management Information System (PROMIS(r) ) methodology, we conducted a comprehensive literature review to identify self-reported survey items regarding patient-reported V&P and childbirth experiences and outcomes (PROs). The V&P/PRO domains were validated by focus groups. We conducted a cross-sectional observational study and fitted a multivariable logistic regression model to each V&P item to describe "who" wanted each item. PRINCIPAL FINDINGS: We identified 5,880 V&P/PRO items that mapped to 19 domains and 58 subdomains. We present results for the 2,250 survey respondents who anticipated a vaginal delivery in a hospital. Wide variation existed regarding each V&P item, and personal characteristics, such as maternal confidence and ability to cope well with pain, were frequent predictors in the models. The resulting preliminary item bank consisted of 60 key personal characteristics and 63 V&P/PROs. CONCLUSIONS: The conceptual framework and preliminary (PROMIS(r) ) item bank presented here provide a foundation for the development of childbirth-specific V&P/PROs. PMID- 29797515 TI - Spontaneous Intracranial Hypotension: 10 Myths and Misperceptions. AB - OBJECTIVE: To discuss common myths and misperceptions about spontaneous intracranial hypotension (SIH), focusing on common issues related to diagnosis and treatment, and to review the evidence that contradicts and clarifies these myths. BACKGROUND: Recognition of SIH has increased in recent years. With increasing recognition, however, has come an increased demand for management by neurologists and headache specialists, some of whom have little prior experience with the condition. This dearth of practical experience, and lack of awareness of recent investigations into SIH, produces heterogeneity in diagnostic and treatment pathways, driven in part by outdated, confusing, or unsubstantiated conceptions of the condition. We sought to address this heterogeneity by identifying 10 myths and misperceptions that we frequently encounter when receiving referrals for suspected or confirmed SIH, and to review the literature addressing these topics. METHODS: Ten topics relevant to diagnosis and treatment SIH were generated by the authors. A search for studies addressing SIH was conducted using PubMed and EMBASE, limited to English language only, peer reviewed publications from inception to 2018. Individual case reports were excluded. The resulting studies were reviewed for relevance to the topics in question. RESULTS: The search generated 557 studies addressing SIH; 75 case reports were excluded. Fifty-four studies were considered to be of high relevance to the topics addressed, and were included in the data synthesis. The topics are presented in the form of a narrative review. CONCLUSIONS: The understanding of SIH has evolved over the recent decades, leading to improvements in knowledge about the pathophysiology of the condition, diagnostic strategies, and expanded treatments. Awareness of these changes, and dispelling outdated misconceptions about SIH, is critical to providing appropriate care for patients and guiding future investigations going forward. PMID- 29797516 TI - Exercising the hepatobiliary-gut axis. The impact of physical activity performance. AB - BACKGROUND: Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways. MATERIALS AND METHODS: This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status. RESULTS: A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body. CONCLUSIONS: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes. PMID- 29797517 TI - Dosimetric characterization of a new directional low-dose rate brachytherapy source. AB - PURPOSE: CivaTech Oncology Inc. (Durham, NC) has developed a novel low-dose rate (LDR) brachytherapy source called the CivaSheet.TM The source is a planar array of discrete elements ("CivaDots") which are directional in nature. The CivaDot geometry and design are considerably different than conventional LDR cylindrically symmetric sources. Thus, a thorough investigation is required to ascertain the dosimetric characteristics of the source. This work investigates the repeatability and reproducibility of a primary source strength standard for the CivaDot and characterizes the CivaDot dose distribution by performing in phantom measurements and Monte Carlo (MC) simulations. Existing dosimetric formalisms were adapted to accommodate a directional source, and other distinguishing characteristics including the presence of gold shield x-ray fluorescence were addressed in this investigation. METHODS: Primary air-kerma strength (SK ) measurements of the CivaDots were performed using two free-air chambers namely, the Variable-Aperture Free-Air Chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center (UWMRRC) and the National Institute of Standards and Technology (NIST) Wide-Angle Free-Air Chamber (WAFAC). An intercomparison of the two free-air chamber measurements was performed along with a comparison of the different assumed CivaDot energy spectra and associated correction factors. Dose distribution measurements of the source were performed in a custom polymethylmethacrylate (PMMA) phantom using GafchromicTM EBT3 film and thermoluminescent dosimeter (TLD) microcubes. Monte Carlo simulations of the source and the measurement setup were performed using MCNP6 radiation transport code. RESULTS: The CivaDot SK was determined using the two free-air chambers for eight sources with an agreement of better than 1.1% for all sources. The NIST measured CivaDot energy spectrum intensity peaks were within 1.8% of the MC predicted spectrum intensity peaks. The difference in the net source-specific correction factor determined for the CivaDot free-air chamber measurements for the NIST WAFAC and UW VAFAC was 0.7%. The dose-rate constant analog was determined to be 0.555 cGy h-1 U-1 . The average difference observed in the estimated CivaDot dose-rate constant analog using measurements and MCNP6 predicted value (0.558 cGy h-1 U-1 ) was 0.6% +/- 2.3% for eight CivaDot sources using EBT3 film, and -2.6% +/- 1.7% using TLD microcube measurements. The CivaDot two-dimensional dose-to-water distribution measured in phantom was compared to the corresponding MC predictions at six depths. The observed difference using a pixel-by-pixel subtraction map of the measured and the predicted dose-to-water distribution was generally within 2-3%, with maximum differences up to 5% of the dose prescribed at the depth of 1 cm. CONCLUSION: Primary SK measurements of the CivaDot demonstrated good repeatability and reproducibility of the free-air chamber measurements. Measurements of the CivaDot dose distribution using the EBT3 film stack phantom and its subsequent comparison to Monte Carlo-predicted dose distributions were encouraging, given the overall uncertainties. This work will aid in the eventual realization of a clinically viable dosimetric framework for the CivaSheet based on the CivaDot dose distribution. PMID- 29797518 TI - Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience. AB - BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. PMID- 29797520 TI - An exploration of the lived experience of professional grief among occupational therapists working in palliative care settings. AB - BACKGROUND/AIM: Occupational therapists who work in palliative care are frequently exposed to the experience of death and dying. Previous occupational therapy research has offered insight into factors that influence feelings relating to death and dying and associated coping strategies. However, existing literature is dated and has not specifically examined the concept of grief. This study addresses this gap in knowledge by exploring the lived experience of professional grief among occupational therapists working in palliative care settings. METHODS: Semi-structured interviews were conducted with six Australian palliative care occupational therapists. The data were collected and analysed using an interpretive phenomenological approach. RESULTS: Four interrelated themes were identified as core to the lived experience of professional grief among participants. These included; 'knowledge of self', 'giving permission for connections and feelings', 'filtering experience' and 'being present at work and at home'. CONCLUSION: Considered in combination, these themes offer a guide for therapists to explore their own experience of and responses to professional grief and, in doing so, foster the development of personalised management strategies. PMID- 29797519 TI - Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy. AB - BACKGROUND: In Phase 3 studies of ustekinumab, a fully human monoclonal IL 12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. METHODS: UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. RESULTS: A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. CONCLUSIONS: Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355. PMID- 29797521 TI - Angiosarcoma arising within a nonfunctioning arteriovenous fistula. PMID- 29797522 TI - Cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis in a patient with X-linked recessive Mendelian susceptibility to mycobacterial diseases with a nuclear factor-kappaB essential modifier mutation. AB - Nuclear factor (NF)-kappaB essential modifier (NEMO), also known as IkappaB kinase subunit-gamma (IKKgamma), is a pivotal molecule in the NF-kappaB signaling pathway. Mutations of NEMO cause incontinentia pigmenti and X-linked ectodermal dysplasia with immunodeficiency. Mendelian susceptibility to mycobacterial diseases (MSMD), which confers an almost selective predisposition to mycobacterial infection, is also caused by NEMO mutations. We herein report the first case of a patient with X-linked recessive (XR) MSMD who developed cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis. The relationship between NEMO mutation and oncogenesis is discussed. PMID- 29797523 TI - Coexistence of mucosa-associated lymphoid tissue lymphoma and systemic sclerosis showing positive for anticentromere antibody and anti-RNA polymerase III antibody: A case report and published work review. PMID- 29797524 TI - Development and validation of a UPLC-MS/MS method for determination of Sarsasapogenin-AA22 in rat plasma and its application to a pharmacokinetic study. AB - A sarsasapogenin derivative, sarsasapogenin-AA22 (AA22), with cyclobutylamine at the 3-hydroxyl position of sarsasapogenin, has great neuroprotective activity in PC12 cells and NO production inhibitory activity in RAW264.7 cell lines. A method was developed to determine AA22 in rat plasma which was further applied to evaluate the pharmacokinetics of AA22 after taking a single dose of AA22. Liquid chromatography tandem mass spectrometry was used in the method, while diosgenin was used as internal standard. A simple protein precipitation based on acetonitrile was utilized. A simple sample cleanup promoted the throughput of the method considerably. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 1 ng/mL for AA22 in plasma. Intra- and inter-day accuracies for AA22 were 92-111 and 100 103%, respectively, and the inter-day precision was <15%. After a single oral dose of 25 mg/kg of AA22, the mean peak plasma concentration of AA22 was 2114 +/- 362 ng/mL at 6 h. The area under the plasma concentration-time curve was 196,098 +/- 69,375 h ng/mL, and the elimination half-life was 8.7 +/- 2.2 h. PMID- 29797525 TI - Four cases of acute infectious urticaria showing significant elevation of plasma D-dimer level. AB - D-dimer, a fibrinolytic end-product, has been regarded as a biomarker indicating the severity of urticaria, especially in chronic urticaria. Regarding acute urticaria, D-dimer level is also suggested to be elevated, which may be significant in comparison with chronic urticaria. However, the clinical features of acute urticaria with concomitant significant elevation of D-dimer level have not been investigated in detail so far. We present four cases of acute urticaria fulfilling the proposed diagnostic criterion of acute infectious urticaria, in which significant elevation of D-dimer level and rapid spontaneous normalization in parallel with the resolution of fever and urticaria occurs. No cases had deep vein thrombosis, disseminated intravascular coagulation and malignancy. All cases responded well to antihistaminic treatment in combination with antibiotics, and their fever and urticaria resolved within 10 days. All cases showed severe wheals persistent for several days resolving with hyperpigmentation. Histologically, infiltration into blood vessel walls and interstitial infiltration of lymphocytes and polymorphonuclear cells were marked in the dermis. In our cases, clinical features accorded with acute infectious urticaria, and their histological features were similar to those of neutrophilic urticaria as described previously. In conclusion, there is a certain group of acute urticaria associated with significant elevation of D-dimer level. These common features of our cases may be characteristic in acute urticaria showing the coagulative and fibrinolytic abnormalities. PMID- 29797526 TI - Development and validation of an LC-MS/MS Method for the quantitation of heparan sulfate in human urine. AB - Heparan sulfate is a linear polysaccharide and serves as an important biomarker to monitor patient response to therapies for MPS III disorder. It is challenging to analyze heparan sulfate intact owing to its complexity and heterogeneity. Therefore, a sensitive, robust and validated LC-MS/MS method is needed to support the clinical studies for the quantitation of heparan sulfate in biofluids under regulated settings. Presented in this work are the results of the development and validation of an LC-MS/MS method for the quantitation of heparan sulfate in human urine using selected high-abundant disaccharides as surrogates. During sample processing, a combination of analytical technologies have been employed, including rapid digestion, filtration, solid-phase extraction and chemical derivatization. The validated method is highly sensitive and is able to analyze heparan sulfate in urine samples from healthy donors. Disaccharide constitution analysis in urine samples from 25 healthy donors was performed using the assay and demonstrated the proof of concept of using selected disaccharides as a surrogate for validation and quantitation. PMID- 29797527 TI - Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients. AB - Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase-1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti-caspase-1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase-1-interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC-MS/MS. Nucleotide-binding oligomerization domain-containing protein-like receptor family CARD domain-containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC-MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non-lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions. PMID- 29797528 TI - Pigmented mammary Paget's disease without underlying carcinoma. PMID- 29797529 TI - Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis. AB - BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy confirmed NASH and NAFLD activity score (NAS) >=4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 +/- 6.6 vs control 28.4 +/- 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 +/- 2.5 vs control 14.1 +/- 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 +/- 6.6 vs "least fit" 17.3 +/- 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 +/- 2.5 vs "least fit" 9.3 +/- 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted. PMID- 29797530 TI - Case of xeroderma pigmentosum group A with West syndrome. PMID- 29797531 TI - HLA-G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss. AB - HLA-G is a nonclassical Class I major histocompatibility complex (MHC) gene. This gene has a limited protein alteration that is produced by alternative splicing and can be important in the preservation of pregnancy. Recent findings suggest that alteration in HLA-G gene expression can lead to pregnancy failure, such as recurrent pregnancy loss (RPL). As the promoter SNPs of the gene may impact the HLA-G expression levels, the study of these SNPs is very important. In this study, for the promoter region of HLA-G gene in the case group (100 women with a history of two or more repeated miscarriages) and the control group (100 women with at least two successful pregnancies), PCR reaction was performed. Thereafter, PCR products were sequenced and the results were compared between the two groups. The results showed that -1573T>C and -1746C>A SNPs in the promoter of the HLA-G gene associated with RPL. The outcome of the haplotype analysis also showed that the association of two haplotypes, including H1 (ATCCAGGTACGCAA) and H2 (CTTCGAGAACGCAG) with RPL, is significant. The results showed that H1 is associated with a decreased and H2 is associated with an increased risk of RPL. These results indicate the importance of the HLA-G promoter SNPs in the pregnancy outcome. But to reach a more definite conclusion, subsequent studies on 3' UTR and other positions with polymorphism in the 5' UTR regions larger samples are necessary. PMID- 29797532 TI - Interaction of microbial pathogens with host exocytic pathways. AB - Many microbial pathogens co-opt or perturb host membrane trafficking pathways. This review covers recent examples in which microbes interact with host exocytosis, the fusion of intracellular vesicles with the plasma membrane. The bacterial pathogens Listeria monocytogenes and Staphylococcus aureus subvert recycling endosomal pathways of exocytosis in order to induce their entry into human cells. By contrast, entry of the protozoan pathogen Trypanosoma cruzi or the virus adenovirus into host cells involves exploitation of lysosomal exocytosis. Toxins produced by Bacillus anthracis or Vibrio cholerae interfere with exocytosis pathways mediated by the GTPase Rab11 and the exocyst complex. By doing so, anthrax or cholera toxins impair recycling of cadherins to cell-cell junctions and disrupt the barrier properties of endothelial cells or intestinal epithelial cells, respectively. Uropathogenic Escherichia coli (UPEC) is expelled from bladder epithelial cells through two different exocytic routes that involve sensing of bacteria in vacuoles by host Toll-like receptor 4 (TLR4) or monitoring of the pH of lysosomes harbouring UPEC. The TLR4 pathway is mediated by multiple Rab GTPases and the exocyst, whereas the other pathway involves exocytosis of lysosomes. Expulsion of UPEC through these pathways is thought to benefit the host. PMID- 29797533 TI - Making Glycine Methyl Ester Chiral. AB - We demonstrate that the simple achiral amino acid glycine as its methyl ester inherits the chiral imprint of methyl lactate upon complexation, resulting in induced vibrational optical activity of the methylene C-H bonds. To mimic conditions of ice on comets that are considered long-term reaction as well as storage entities for (organic) molecules, we employ the matrix isolation technique in conjunction with vibrational circular dichroism spectroscopy and DFT computations. The observed chirality transfer is likely a key element for the realization of concepts rationalizing chirogenesis, that is, the generation of a chiral imbalance. PMID- 29797534 TI - Malnutrition is independently associated with skin tears in hospital inpatient setting-Findings of a 6-year point prevalence audit. AB - Skin tears cause pain, increased length of stay, increased costs, and reduced quality of life. Minimal research reports the association between skin tears, and malnutrition using robust measures of nutritional status. This study aimed to articulate the association between malnutrition and skin tears in hospital inpatients using a yearly point prevalence of inpatients included in the Queensland Patient Safety Bedside Audit, malnutrition audits and skin tear audits conducted at a metropolitan tertiary hospital between 2010 and 2015. Patients were excluded if admitted to mental health wards or were <18 years. A total of 2197 inpatients were included, with a median age of 71 years. The overall prevalence of skin tears was 8.1%. Malnutrition prevalence was 33.5%. Univariate analysis demonstrated associations between age (P ? .001), body mass index (BMI) (P < .001) and malnutrition (P ? .001) but not gender (P = .319). Binomial logistic regression analysis modelling demonstrated that malnutrition diagnosed using the Subjective Global Assessment was independently associated with skin tear incidence (odds ratio, OR: 1.63; 95% confidence interval, CI: 1.13-2.36) and multiple skin tears (OR 2.48 [95% CI 1.37-4.50]). BMI was not independently associated with skin tears or multiple skin tears. This study demonstrated independent associations between malnutrition and skin tear prevalence and multiple skin tears. It also demonstrated the limitations of BMI as a nutritional assessment measure. PMID- 29797535 TI - Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes through [3,3] Sigmatropic Rearrangement. AB - We herein report a robust catalyst-free cross-coupling between ArI(OAc)2 and alpha-stannyl nitriles, aided by TMSOTf. The transformation introduces a cyanoalkyl group to the ortho position of ArI(OAc)2 and simultaneously reduces the aryl iodine(III) to iodide, thus providing alpha-(2-iodoaryl) nitrile as the product. This transformation could be completed within 5 min at -78 degrees C and features superb functional-group tolerance and efficient scalability. DFT calculations indicate that the formation of a ketenimine(aryl)iodonium intermediate and subsequent [3,3]-sigmatropic rearrangement are involved as key steps. PMID- 29797536 TI - Evaluation of a community-based training to promote responsible self-medication in East Java, Indonesia. AB - OBJECTIVE: To explore pharmacist/pharmacy staff trainers' perspectives on conducting community-based training to promote responsible self-medication, and to evaluate knowledge gained among community representatives participating in the training. METHODS: Training was conducted in four districts/cities in East Java, Indonesia in 2016. A pre-test/post-test study was used to evaluate the knowledge of 129 community representatives (participants) before/after the training; pre test and post-test scores as well as absolute gain were determined. Four focus group discussions with 20 pharmacist/pharmacy staff (trainers) were conducted after the training, and the data were thematically analysed. KEY FINDINGS: Overall mean test scores for community representatives significantly improved from 14.11 to 15.70 after the training (P < 0.001). The average total absolute gain was 1.85 (95% CI 1.29 to 2.39). To reach local communities, trainers suggested improvements to the content and structure of the module, training aids, trainer competency, approach and time allocation. CONCLUSIONS: Community-based training provides a potential strategy to improve community knowledge of medications. Findings from this study should inform strategies for a broader uptake amongst local communities in Indonesia. PMID- 29797537 TI - The role of the maternal and fetal inflammatory response in retinopathy of prematurity. AB - PROBLEM: There is a paucity of research on the contribution of placental inflammation to severe retinopathy of prematurity (ROP). METHOD OF STUDY: A retrospective cohort study (n = 1217) was conducted of infants screened for ROP (2006-2016). The outcomes of the study were severe ROP (type 1 or type 2 ROP) and low grade ROP. We categorized the placental pathology as the presence of (i) maternal plus fetal inflammatory response, (ii) maternal inflammatory response only, (iii) fetal inflammatory response only and, (iv) no evidence of a maternal or fetal inflammatory response. The data were analyzed using univariate and multivariate logistic regression analyses (P < .05). RESULTS: In this cohort, the number of infants with the maternal plus fetal inflammatory response, the maternal inflammatory response only, the fetal inflammatory response only, and no maternal or fetal inflammatory response was 305 (25%), 82 (7%), 8 (1%), and 822 (67%), respectively. Adjusted for covariates, the maternal plus fetal inflammatory response was a significant risk factor for severe ROP (AOR = 2.6, 95% CI 1.1-5.9, P = .03). None of the categories of placental inflammation were significantly associated with low grade ROP. CONCLUSION: Placental pathology distinguished by the maternal plus fetal inflammatory response was a significant risk factor for severe ROP. Our study supports a link between intrauterine inflammatory events and the subsequent development of severe ROP. PMID- 29797539 TI - Group IV Monochalcogenides MX (M=Ge, Sn; X=S, Se) as Chemical Anchors of Polysulfides for Lithium-Sulfur Batteries. AB - Although rechargeable lithium-sulfur batteries are considered as advanced energy systems, their practical implementation is impeded by many factors, in particular the rapid capacity fade and low Coulomb efficiency caused by the shuttle effect. To overcome this problem for achieving longer cycle life and higher rate performance, anchoring materials for lithium polysulfides are highly desirable. In this work, for the first time, we report phosphorene-like MX (M=Ge, Sn; X=S, Se) monolayers as promising anchoring materials to restrain the lithium polysulfides shuttling. Our study provides fundamental selection criteria for the effective suppression of the polysulfides shuttling. Adsorption calculations reveal that polysulfide capture by the MX is through chemisorption with a suitable range of adsorption energies. Morever, we show that excellent surface diffusion of Li and polysulfides endow a fast charge/discharge rate for lithium sulfur batteries. Graphene with desirable electronic properties is constructed to improve the electrical conductivity in the new graphene@MX heterostructures. Based on the strong anchoring ability, improved rate capability, and enhanced conductivity, MX-based composites hold great promise as an anchoring material for high-energy lithium-sulfur batteries. PMID- 29797538 TI - Extracellular RNA profiles with human age. AB - Circulating extracellular RNAs (exRNAs) are potential biomarkers of disease. We thus hypothesized that age-related changes in exRNAs can identify age-related processes. We profiled both large and small RNAs in human serum to investigate changes associated with normal aging. exRNA was sequenced in 13 young (30-32 years) and 10 old (80-85 years) African American women to identify all RNA transcripts present in serum. We identified age-related differences in several RNA biotypes, including mitochondrial transfer RNAs, mitochondrial ribosomal RNA, and unprocessed pseudogenes. Age-related differences in unique RNA transcripts were further validated in an expanded cohort. Pathway analysis revealed that EIF2 signaling, oxidative phosphorylation, and mitochondrial dysfunction were among the top pathways shared between young and old. Protein interaction networks revealed distinct clusters of functionally-related protein-coding genes in both age groups. These data provide timely and relevant insight into the exRNA repertoire in serum and its change with aging. PMID- 29797540 TI - Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia. AB - PROBLEM: B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta. METHOD OF STUDY: Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13 weeks' gestation with elevated risk for PE (n = 48) and women without elevated risk for PE (n = 47). In the third trimester, sB7-H4 serum levels (n = 166) and B7-H4 mRNA expression in the placenta (n = 54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls. RESULTS: In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P < .0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63 ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P = .01 and P = .006, respectively) and late-onset PE (P = .03 and P = .004, respectively) compared to healthy controls, but not compared to FGR. CONCLUSION: sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE. PMID- 29797541 TI - MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM 2/p53 pathway after traumatic spinal cord injury in rats. AB - The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t-SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba-1, cleaved caspase 3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell based mechanical injury model was also conducted using SH-SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p-Akt, were gradually increased and after t-SCI. Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM 2/p53 pathway after t-SCI. Therefore, MANF might be a potential treatment for patients with t-SCI.(c) 2018 BioFactors, 2018. PMID- 29797542 TI - Electrochemical Double-Layer Capacitor Energized by Adding an Ambipolar Organic Redox Radical into the Electrolyte. AB - Carbon-based electrochemical double-layer capacitors (EDLCs) generally exhibit high power and long life, but low energy density/capacitance. Pore/morphology optimization and pseudo-capacitive materials modification of carbon materials have been used to improve electrode capacitance, but leading to the consumption of tap density, conductivity and stability. Introducing soluble redox mediators into electrolyte is a promising alternative to improve the capacitance of electrode. However, it is difficult to find one redox mediator that can provide additional capacitance for both positive and negative electrodes simultaneously. Here, an ambipolar organic radical, 2, 2, 6, 6-tetramethylpiperidinyloxyl (TEMPO) is first introduced to the electrolyte, which can substantially contribute additional pseudo-capacitance by oxidation at the positive electrode and reduction at the negative electrode simultaneously. The EDLC with TEMPO mediator delivers an energy density as high as 51 Wh kg-1 , 2.4 times of the capacitor without TEMPO, and a long cycle stability over 4000 cycles. The achieved results potentially point a new way to improve the energy density of EDLCs. PMID- 29797543 TI - The serine/threonine protein kinase of Streptococcus suis serotype 2 affects the ability of the pathogen to penetrate the blood-brain barrier. AB - Streptococcus suis serotype 2 (SS2) is a zoonotic agent that causes meningitis in humans and pigs. However, the mechanism whereby SS2 crosses the microvasculature endothelium of the brain is not understood. In this study, transposon (TnYLB-1) mutagenesis was used to identify virulence factors potentially associated with invasive ability in pathogenic SS2. A poorly invasive mutant was identified and was found to contain a TnYLB-1 insertion in the serine/threonine kinase (stk) gene. Transwell chambers containing hBMECs were used to model the blood-brain barrier (BBB). We observed that the SS2 wild-type ZY05719 strain crossed the BBB model more readily than the mutant strain. Hence, we speculated that STK is associated with the ability of crossing blood-brain barrier in SS2. In vitro, compared with ZY05719, the ability of the stk-deficient strain (Deltastk) to adhere to and invade both hBMECs and bEnd.3 cells, as well as to cross the BBB, was significantly attenuated. Immunocytochemistry using antibodies against claudin-5 in bEnd.3 cells showed that infection by ZY05719 disrupted BBB tight junction proteins to a greater extent than in infection by Deltastk. The studies revealed that SS2 initially binds at or near intercellular junctions and crosses the BBB via paracellular traversal. Claudin-5 mRNA levels were indistinguishable in ZY05719- and Deltastk-infected cells. This result indicated that the decrease of claudin-5 was maybe induced by protein degradation. Cells infected by ZY05719 exhibited higher ubiquitination levels than cells infected by Deltastk. This result indicated that ubiquitination was involved in the degradation of claudin 5. Differential proteomic analysis showed that E3 ubiquitin protein ligase HECTD1 decreased by 1.5-fold in Deltastk-infected bEnd.3 cells relative to ZY05719 infected cells. Together, the results suggested that STK may affect the expression of E3 ubiquitin ligase HECTD1 and subsequently increase the degradation of claudin-5, thus enabling SS2 to traverse the BBB. PMID- 29797544 TI - Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography. AB - In preclinical vision research, cell grading in small animal models is essential for the quantitative evaluation of intraocular inflammation. Here, we present a new and practical optical coherence tomography (OCT) image analysis method for the automated detection and counting of aqueous cells in the anterior chamber (AC) of a rodent model of uveitis. Anterior segment OCT images are acquired with a 100 kHz swept-source OCT system. The proposed method consists of 2 steps. In the first step, we first despeckle and binarize each OCT image. After removing AS structures in the binary image, we then apply area thresholding to isolate cell like objects. Potential cell candidates are selected based on their best fit to roundness. The second step performs the cell counting within the whole AC, in which additional cell tracking analysis is conducted on the successive OCT images to eliminate redundancy in cell counting. Finally, 3D cell grading using the proposed method is demonstrated in longitudinal OCT imaging of a mouse model of anterior uveitis in vivo. Rendering of anterior segment (orange) of mouse eye and automatically counted anterior chamber cells (green). Inset is a top view of the rendering, showing the cell distribution across the anterior chamber. PMID- 29797545 TI - Validation of "Wound QoL" Hebrew version disease-specific questionnaire for patients with lower extremity ulcerations. AB - The slow healing process and high recurrence rate of lower extremity ulcerations (LEU) impose a considerable medical and economic burden and affect quality of life (QoL). Analyses of LEU-related QoL in Israel are limited due to lack of a validated Hebrew disease-specific evaluation instrument. The aim of this study was to validate the disease-specific Hebrew "Wound QoL" questionnaire. The validation of the "Wound QoL" disease-specific instrument, translated from English to Hebrew, was based on a comparison with the valid Hebrew version of the SF12v.2 health-related questionnaire. The convenience sample for the "Wound QoL" validation (n = 32) was obtained from patient populations in the Maccabi Health Services' outpatient clinics at the northern and southern parts of Israel. The study was conducted between June and September 2017. Face/construct validity was accepted by specialists' consensus. Internal consistency assessed by Cronbach's alpha was .893. Concurrent validity reflected by Pearson's correlations between the tools was in the range of 0.830 to 0.950. The Wound QoL Hebrew version is a valid and reliable instrument suitable for implementation in an Israeli cultural environment. PMID- 29797546 TI - Preparation and purification of canthinone and beta-carboline alkaloids from Picrasma quassioides based on bioautography and mass-spectrometry-directed autopurification system. AB - Picrasma quassioides (D. Don) Benn. is a widely used traditional Chinese medicine for anti-inflammation and antibiosis. Canthinone and beta-carboline alkaloids are the main characteristic constituents that possess diverse pharmacological effects, such as anti-inflammatory and anti-infectious properties. In this study, bioautography in thin-layer chromatography indicated that the antiradical activity compound may be alkaloids. Then, a simple, fast, and efficient method was established for the separation and purification of two types of alkaloids from P. quassioides by mass-spectrometry-directed autopurification system. Eight alkaloids were isolated and purified in this one-step methodology. Among them, five compounds (3, 95.1%, 58.8 mg; 4, 98.4%, 71.7 mg; 6, 97.8%, 365.4 mg; 7, 97.7%, 172.7 mg; 8, 98.2%, 180.3 mg) were obtained in large amounts with extremely high purities. Then, the antiradical activities of the isolates showed that 4-methoxy-5-hydroxycanthin-6-one (6) exhibited obvious 1,1-diphenyl-2-picryl hydrazyl free radical scavenging activity with an IC50 value of 84.037 MUM. This study offers a new method for the preparation of targeted bioactive alkaloids in P. quassioides. This work also provides a reference for the separation of other targeted chemical components with potential activities from traditional Chinese herbal medicines. PMID- 29797547 TI - Assessing indocyanine green pharmacokinetics in mouse liver with a dynamic diffuse fluorescence tomography system. AB - Fluorescence pharmacokinetic rates in tissues can provide additional specific and quantitative physiological and pathological information for evaluating organ function. This modality requires a highly sensitive diffuse fluorescence tomography (DFT) working in dynamic way to finally extract the pharmacokinetic rates from the measured pharmacokinetics-associated temporally varying boundary intensity, normally with the support of a priori anatomy. This paper is devoted to study pharmacokinetics of indocyanine green (ICG) in mouse liver based on synergistic dynamic-DFT and X-ray computer tomography (XCT): A highly sensitive dynamic DFT system of CT-scanning mode working with parallel 4 photomultiplier tube photon-counting channels generates informative and instantaneous sampling datasets; An XCT system provides priori information of the target localization for improvement of the reconstruction quality; An analysis procedure extracts the pharmacokinetic rates from the reconstructed ICG concentration-time curves, using the Gauss-Newton scheme for fitting to a 2-compartment model. The uptake and excretion rates of ICG which were obtained in livers of 10 healthy mice in the in vivo experiments can be used to quantitatively evaluate liver function. The results can validate the effectiveness of both the imaging measurements system and pharmacokinetic analysis method. PMID- 29797548 TI - Conservation of the behavioral and transcriptional response to social experience among Drosophilids. AB - While social experience has been shown to significantly alter behaviors in a wide range of species, comparative studies that uniformly measure the impact of a single experience across multiple species have been lacking, limiting our understanding of how plastic traits evolve. To address this, we quantified variations in social feeding behaviors across 10 species of Drosophilids, tested the effect of altering rearing context on these behaviors (reared in groups or in isolation) and correlated observed behavioral shifts to accompanying transcriptional changes in the heads of these flies. We observed significant variability in the extent of aggressiveness, the utilization of social cues during food search, and social space preferences across species. The sensitivity of these behaviors to rearing experience also varied: socially naive flies were more aggressive than their socialized conspecifics in some species, and more reserved or identical in others. Despite these differences, the mechanism of socialization appeared to be conserved within the melanogaster subgroup as species could cross-socialize each other, and the transcriptional response to social exposure was significantly conserved. The expression levels of chemosensory-perception genes often varied between species and rearing conditions, supporting a growing body of evidence that behavioral evolution is driven by the differential regulation of this class of genes. The clear differences in behavioral responses to socialization observed in Drosophilids make this an ideal system for continued studies on the genetic basis and evolution of socialization and behavioral plasticity. PMID- 29797549 TI - Minimizing polymerase biases in metabarcoding. AB - DNA metabarcoding is an increasingly popular method to characterize and quantify biodiversity in environmental samples. Metabarcoding approaches simultaneously amplify a short, variable genomic region, or "barcode," from a broad taxonomic group via the polymerase chain reaction (PCR), using universal primers that anneal to flanking conserved regions. Results of these experiments are reported as occurrence data, which provide a list of taxa amplified from the sample, or relative abundance data, which measure the relative contribution of each taxon to the overall composition of amplified product. The accuracy of both occurrence and relative abundance estimates can be affected by a variety of biological and technical biases. For example, taxa with larger biomass may be better represented in environmental samples than those with smaller biomass. Here, we explore how polymerase choice, a potential source of technical bias, might influence results in metabarcoding experiments. We compared potential biases of six commercially available polymerases using a combination of mixtures of amplifiable synthetic sequences and real sedimentary DNA extracts. We find that polymerase choice can affect both occurrence and relative abundance estimates and that the main source of this bias appears to be polymerase preference for sequences with specific GC contents. We further recommend an experimental approach for metabarcoding based on results of our synthetic experiments. PMID- 29797550 TI - W(OTf)6 -Catalyzed Synthesis of gamma-Lactones by Ring Contraction of Macrolides or Ring Closing of Terminal Hydroxyfatty Acids in Ionic Liquid. AB - gamma-Lactones are an important class of fine chemical products and are widely used in perfumes, medicines, pesticides, dyes, and other fields. Herein, a new method for gamma-lactones preparation based on ring contraction was developed. Starting from macrolides, W(OTf)6 was used to catalyze the ring-opening polymerization then depolymerization. The depolymerization step was not a common ring-closing process, and the carbon number of the ring was reduced one by one by rearrangement to form the most thermodynamically stable five-membered ring compounds. gamma-Caprolactone (180 degrees C for 10 h) was obtained in a yield of 94 % when [EMIM]OTf was used as the solvent, and the yield of isolated product was up to 85 %. The interaction of various components and the reaction mechanism were studied by FTIR spectroscopy and 1 H NMR spectroscopy, respectively. Furthermore, gamma-lactones could be produced when the substrate was extended to terminal hydroxyfatty acids. Unexpectedly, the catalyst was poisoned by 1 equivalent of H2 O added during the process and thus the yield decreased greatly. The reaction is green and simple, and proceeds in one pot with high atom economy (100 % for macrolides and with water as the only byproduct for terminal hydroxyfatty acid), which provides a promising approach to synthesizing gamma lactones. PMID- 29797552 TI - Response to Camacho. PMID- 29797553 TI - Response to Harcombe. PMID- 29797551 TI - Combination vinblastine, prednisolone and toceranib phosphate for treatment of grade II and III mast cell tumours in dogs. AB - This retrospective study evaluates the progression-free interval and survival outcomes of 40 canine (Canis familiaris) patients with Patnaik grade II and III mast cell tumours treated with combination vinblastine, prednisolone and toceranib phosphate from 2011 to 2015. Patients were subdivided into three groups; patients who received neoadjuvant therapy for poorly operable lesions, patients who received adjuvant therapy following surgical resection and patients being palliated for gross metastatic disease. Median survival time (MST) for the neoadjuvant group was not reached. Median survival time for the remaining groups was 893 days and 218 days, respectively. This combination demonstrated response in 90% (26/29) patients with measurable disease. The predominant side effects related to this chemotherapy combination were gastrointestinal in origin. Further prospective studies are required to further validate the efficacy of this treatment protocol. PMID- 29797554 TI - Comments on "Low carbohydrate diets may increase risk of neural tube defects". PMID- 29797557 TI - BMI Trajectories: What Do They Really Teach Us? PMID- 29797555 TI - Impact of Early-Life Weight Status on Cognitive Abilities in Children. AB - OBJECTIVE: Whether obesity is associated with childhood cognition is unknown. Given the sensitivity of the developing brain to environmental factors, this study examined whether early-life weight status was associated with children's cognition. METHODS: Using data from mother-child pairs enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006), children's early-life weight status was assessed using weight-for-length/height standard deviation (SD) scores. A battery of neuropsychological tests was administered to assess cognition, executive function, and visual-spatial abilities at ages 5 and 8 years. Using linear mixed models, associations between early-life weight status and cognition were estimated. RESULTS: Among 233 children, 167 were lean (<=1 SD) and 48 were nonlean (>1 SD). After covariate adjustment, the results suggest that full-scale intelligence quotient scores decreased with a 1-unit increase in weight-for-height SD score (beta = -1.4, 95% CI: -3.0 to 0.1). For individual component scores, with a 1-unit increase in weight-for-height SD score, perceptual reasoning (beta = -1.7, 95% CI: -3.3 to 0.0) and working memory (beta: -2.4, CI: -4.4 to -0.4) scores decreased. Weight status was generally not associated with other cognition measures. CONCLUSIONS: Within this cohort of typically developing children, early-life weight status was inversely associated with children's perceptual reasoning and working memory scores and possibly with full-scale intelligent quotient scores. PMID- 29797556 TI - Does the Immigrant Advantage in Overweight/Obesity Persist over Time in Mexican American Youth? NHANES 1988-1994 to 2005-2014. AB - OBJECTIVE: To examine whether the relationship between nativity and overweight/obesity has changed over time among Mexican American children and to investigate the implications of this pattern on overweight/obesity disparities relative to non-Hispanic white children. METHODS: Using cross-sectional data from Mexican American and non-Hispanic white children aged 4 to 17 years participating in the National Health and Nutrition Examination Surveys (1988-1994 [N = 4,720] and 2005-2014 [N = 7,275]) log-binomial regression was used to calculate prevalence ratios (PRs) of overweight/obesity by nativity status adjusting for sociodemographic covariates, survey period, and a nativity-by-survey period interaction. A separate covariate-adjusted model tested a three-level interaction between ethnicity, nativity, and survey period that included non-Hispanic white children. RESULTS: In 1988-1994, foreign-born Mexican Americans had significantly lower prevalence of overweight/obesity compared with US-born Mexican Americans (PR = 0.75, 95% CI: 0.61-0.94). However, by 2005-2014, the nativity gap in overweight/obesity had closed (PR = 0.94, 95% CI: 0.84-1.07). Moreover, while foreign-born Mexican Americans had the lowest levels of overweight/obesity in 1988-1994, by 2005-2014, foreign-born and US-born Mexican Americans had comparable estimates, both significantly higher than that of non-Hispanic white individuals. CONCLUSIONS: Although overweight/obesity disparities between Mexican Americans and non-Hispanic white Americans had previously been specific to US born Mexican Americans, disparities in more recent years have extended to foreign born Mexican Americans. PMID- 29797558 TI - Differences in the Neighborhood Retail Food Environment and Obesity Among US Children and Adolescents by SNAP Participation. AB - OBJECTIVE: The goal of this study was to understand the association between children's neighborhood food access and overweight/obesity in a national sample of US households, and whether this association differs by Supplemental Nutrition Assistance Program (SNAP) participation or household purchases. METHODS: Data were obtained from the National Household Food Acquisition and Purchase Survey (2012-2013; n = 3,748 children aged 2 to 18 years). Logistic regression was used to examine associations between neighborhood retail food access (<=1 mile from home), food purchases (including sugary beverages), and overweight/obesity, stratified by SNAP status (1,720 participants, 453 eligible nonparticipants, 1,575 SNAP ineligible). Store types included supermarkets/grocery, combination grocery/other (independent drug, dollar, and general stores), convenience, fast food, and non-fast food restaurants. RESULTS: Odds of childhood overweight/obesity (OR [95% CI]) were higher with greater access to combination grocery/other stores overall (1.10 [1.03-1.17]) and for children in SNAP (1.14 [1.05-1.24]). Eligible non-SNAP children had higher odds of overweight/obesity with greater access to convenience stores (1.11 [1.04-1.18]). The average child lived in a household with 6.3% of total spending at food outlets on sugary beverages (SNAP: 8.3%, eligible non-SNAP: 7.7%, SNAP ineligible: 5.5%). CONCLUSIONS: Greater neighborhood access to combination grocery/other stores is associated with higher obesity prevalence for children overall and those in SNAP. PMID- 29797560 TI - Plastid genomes reveal recurrent formation of allopolyploid Fragaria. AB - PREMISE OF THE STUDY: Recurrent formation of polyploid taxa is a common observation in many plant groups. Haploid, cytoplasmic genomes like the plastid genome can be used to overcome the problem of homeologous genes and recombination in polyploid taxa. Fragaria (Rosaceae) contains several octo- and decaploid species. We use plastome sequences to infer the plastid ancestry of these taxa with special focus on the decaploid Fragaria cascadensis. METHODS: We used genome skimming of 96 polyploid Fragaria samples on a single Illumina HiSeq 3000 lane to obtain whole plastome sequences. These sequences were used for phylogenetic reconstructions and dating analyses. Ploidy of all samples was inferred with flow cytometry, and plastid inheritance was examined in a controlled cross of F. cascadensis. KEY RESULTS: The plastid genome phylogeny shows that only the octoploid F. chiloensis is monophyletic, all other polyploid taxa were supported to be para- or polyphyletic. The decaploid Fragaria cascadensis has biparental plastid inheritance and four different plastid donors. Diversification of the F. cascadensis clades occurred in the last 230,000 years. The southern part of its distribution range harbors considerably higher genetic diversity, suggestive of a potential refugium. CONCLUSIONS: Fragaria cascadensis had at least four independent origins from parents with different plastomes. In contrast, para- and polyphyletic taxa of the octoploid Fragaria species are best explained by incomplete lineage sorting and/or hybridization. Biogeographic patterns in F. cascadensis are probably a result of range shift during the last glacial maximum. PMID- 29797559 TI - Energy Expenditure in Pregnant Women with Obesity Does Not Support Energy Intake Recommendations. AB - OBJECTIVE: This study aimed to identify factors that may predispose women to excess gestational weight gain (GWG). METHODS: Seventy-two healthy women with obesity (30 class I, 24 class II, 18 class III) expecting a singleton pregnancy were studied at 13 to 16 weeks gestation. Energy expenditure (EE) was measured during sleep (SleepEE, average EE from 0200-0500 hours) in a whole-room calorimeter, and total daily EE (TDEE) over 7 days using doubly labeled water. Glucose, insulin, thyroid hormones, and catecholamines were measured. RESULTS: Body composition explained 70% variability in SleepEE, and SleepEE accounted for 67% to 73% of TDEE. Though there was no evidence of consistent low metabolism, there was considerable variability. Low SleepEE was associated with insulin resistance and low triiodothyronine concentrations (both P = 0.01). Physical activity level was 1.47 +/- 0.02. For women with SleepEE within 100 kcal/d of their predicted EE, TDEE was significantly less than the estimate (2,530 +/- 91 vs. 2,939 kcal/d; P < 0.001) provided from the most recent gestational energy requirement model. CONCLUSIONS: Pregnant women with obesity are inactive, possibly predisposing them to excess GWG. Current energy requirement models overestimate activity and may promote excess GWG in women with obesity. Furthermore, the observed large interindividual variability in basal metabolism may be important to consider when assessing the risk for excess GWG. PMID- 29797561 TI - NEAT1 upregulates TGF-beta1 to induce hepatocellular carcinoma progression by sponging hsa-mir-139-5p. AB - Increasing evidence has shown that the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) play important roles in cell proliferation, migration, and invasion in various tumors. In our current study, we concentrated on the biological mechanisms of NEAT1 in hepatocellular carcinoma (HCC) development. It was found that NEAT1 was significantly increased in human HCC cell lines including Hep3B, LM3, MHCC97L, SK-hep1, and HepG2 cells compared to the normal human liver cell line LO2. Meanwhile, we observed that hsa-miR-139-5p was greatly decreased in HCC cells, which suggested a negative correlation between NEAT1 and hsa-mir-139-5p. In addition, NEAT1 downregulation can restrain HCC cell growth, migration, and invasion. Consistently, overexpression of hsa-mir-139-5p exerted a similar phenomenon. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay confirmed that NEAT1 can function as a ceRNA by sponging hsa-mir-139-5p. In addition, TGF-beta1 was identified as a downstream target of hsa-mir-139-5p and hsa-mir-139-5p overexpression was able to suppress TGF-beta1 levels. Furthermore, it was indicated that TGF-beta1 inhibition can inhibit HCC cell growth, migration, and invasion ability. Taken these together, we speculated that NEAT1 can modulate TGF-beta1 expression by sponging hsa-mir-139-5p in HCC. These data indicates that targeting the NEAT1/hsa-mir-139-5p/TGF-beta1 axis could be a new strategy for HCC. PMID- 29797562 TI - Long non-coding RNA FEZF1-AS1 promotes breast cancer stemness and tumorigenesis via targeting miR-30a/Nanog axis. AB - Long non-coding RNAs (lncRNAs) have been verified to modulate the tumorigenesis of breast cancer at multiple levels. In present study, we aim to investigate the role of lncRNA FEZF1-AS1 on breast cancer-stem like cells (BCSC) and the potential regulatory mechanism. In breast cancer tissue, lncRNA FEZF1-AS1 was up regulated compared with controls and indicated poor prognosis of breast cancer patients. In vitro experiments, FEZF1-AS1 was significantly over-expressed in breast cancer cells, especially in sphere subpopulation compared with parental subpopulation. Loss-of-functional indicated that, in BCSC cells (MDA-MB-231 CSC, MCF-7 CSC), FEZF1-AS1 knockdown reduced the CD44+ /CD24- rate, the mammosphere forming ability, stem factors (Nanog, Oct4, SOX2), and inhibited the proliferation, migration and invasion. In vivo, FEZF1-AS1 knockdown inhibited the breast cancer cells growth. Bioinformatics analysis tools and series of validation experiments confirmed that FEZF1-AS1 modulated BCSC and Nanog expression through sponging miR-30a, suggesting the regulation of FEZF1-AS1/miR 30a/Nanog. In summary, our study validate the important role of FEZF1-AS1/miR 30a/Nanog in breast cancer stemness and tumorigenesis, providing a novel insight and treatment strategy for breast cancer. PMID- 29797563 TI - The critical role of fossils in inferring deep-node phylogenetic relationships and macroevolutionary patterns in Cornales. AB - PREMISE OF THE STUDY: The basal asterid order, Cornales, experienced a rapid radiation during the Cretaceous, which has made it difficult to elucidate the early evolution of the order using extant taxa only. Recent paleobotanical studies, however, have begun to shed light on the early diversification of Cornales. Herein, fossils are directly incorporated in phylogenetic and quantitative morphological analyses to reconstruct early cornalean evolution. METHODS: A morphological matrix of 77 fruit characters and 58 taxa (24 extinct) was assembled. Parsimony analyses including and excluding fossils were conducted. A fossil inclusive tree was time-scaled to visualize the timing of the initial cornalean radiation. Disparity analyses were utilized to infer the morphological evolution of cornaleans with drupaceous fruits. KEY RESULTS: Fossil inclusive and exclusive parsimony analyses resulted in well-resolved deep-node relationships within Cornales. Resolution in the fossil inclusive analysis is substantially higher, revealing a basal grade including Loasaceae, Hydrangeaceae, Hydrostachyaceae, Grubbiaceae, a Hironoia+Amersinia clade, and Curtisiaceae, respectively, that leads to a "core" group containing a clade comprising a Cretaceous grade leading to clade of Nyssaceae, Mastixiaceae, and Davidiaceae that is sister to a Cornaceae+Alangiaceae clade. The time-scaled tree indicates that the initial cornalean diversification occurred before 89.8 Ma. Disparity analyses suggest the morphological diversity of Cornales peaked during the Paleogene. CONCLUSIONS: Phylogenetic analyses clearly demonstrate that novel character mosaics of Cretaceous cornaleans play a critical role in resolving deep node relationships within Cornales. The post-Cretaceous increase of cornalean disparity is associated with a shift in morphospace occupation, which can be explained from ecological and developmental perspectives. PMID- 29797565 TI - Amplitude by Peak Interaction but No Evidence of Auditory Mismatch Response Deficits to Frequency Change in Preschool-Aged Children with Fetal Alcohol Spectrum Disorders. AB - BACKGROUND: Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with fetal alcohol spectrum disorders (FASD). METHODS: Participants in this study were 9 children with a FASD and 17 control children (Control) aged 3 to 6 years. Participants underwent magnetoencephalography and structural magnetic resonance imaging scans separately. We compared groups on neurophysiological mismatch negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1,000 Hz) and rare (1,200 Hz) tones were presented at 72 dB. RESULTS: There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200 ms after stimulus presentation in the difference time course between frequent and infrequent tones. Examining the time courses to the frequent and infrequent tones separately, repeated measures analysis of variance with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p = 0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields. CONCLUSIONS: The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-aged children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in children with FASD. PMID- 29797566 TI - Roles of Vanadium and Nitrogen in Photocatalytic Activity of VN-Codoped TiO2 Photocatalyst. AB - In the present manuscript, we explore the VN-codoped TiO2 system intended to understand the role played by each dopant in synergistic enhancement in performance of TiO2 photocatalyst. The photocatalytic decomposition of organic pollutants in aqueous solution under visible light was used as a probe reaction to evaluate the performance of VN-codoped TiO2 samples with different V and N concentrations. An optical measurement of VN-codoped TiO2 shows considerable improved visible light absorption with increase in V-concentration as compared to increase in N concentration, which was due to the effective narrowing of the band gap by V-doping. The energy levels formed by N-dopants act as the trapping centers for photogenerated holes to suppress recombination process as indicated by PL and TRPL results. It is also observed that at high V-concentrations recombination centers are created in the form of oxygen vacancies as indicated by XPS and PL. In VN-codoped TiO2 , addition of N partially fills these oxygen vacancies to reduce the number of recombination centers and prolong the lifetime of charge carriers. Thus, V improves the visible light absorption while N reduces the recombination of electron-hole pairs, thus creating the synergistic effect to produce three times better performance than pure TiO2 . PMID- 29797567 TI - TANK-binding kinase 1 and Janus kinase 2 play important roles in the regulation of mitogen-activated protein kinase phosphatase-1 expression after toll-like receptor 4 activation. AB - Inflammation is a response that protects the body from pathogens. Through several inflammatory signaling pathways mediated by various families of transcription factors, such as nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), interferon regulatory factors (IRFs), and signal transducers and activators of transcription (STATs), various inflammatory cytokines and chemokines are induced and inflammatory responses are boosted. Simultaneously, inhibitory systems are activated and provide negative feedback. A typical mechanism by which this process occurs is that inflammatory signaling molecules upregulate mitogen activated protein kinase phosphatase-1 (MKP1) expression. Here, we investigated how kinases regulate MKP1 expression in lipopolysaccharide-triggered cascades. We found that p38 and c-Jun N-terminal kinase (JNK) inhibitors decreased MKP1 expression. Using specific inhibitors, gene knockouts, and gene knockdowns, we also found that tumor necrosis factor receptor-associated factor family member associated nuclear factor kappaB activator (TANK)-binding kinase 1 (TBK1) and Janus kinase 2 (JAK2) are involved in the induction of MKP1 expression. By analyzing JAK2-induced activation of STATs, STAT3-specific inhibitors, promoter binding sites, and STAT3-/- cells, we found that STAT3 is directly linked to TBK1 mediated and JAK2-mediated induction of MKP1 expression. Our data suggest that MKP1 expression can be differentially regulated by p38, JNK, and the TBK1-JAK2 STAT3 pathway after activation of toll-like receptor 4 (TLR4). These data also imply crosstalk between the AP-1 pathway and the IRF3 and STAT3 pathways. PMID- 29797568 TI - Excessive training induces molecular signs of pathologic cardiac hypertrophy. AB - Chronic exercise induces cardiac remodeling that promotes left ventricular hypertrophy and cardiac functional improvement, which are mediated by the mammalian or the mechanistic target of rapamycin (mTOR) as well as by the androgen and glucocorticoid receptors (GRs). However, pathological conditions (i.e., chronic heart failure, hypertension, and aortic stenosis, etc.) also induce cardiac hypertrophy, but with detrimental function, high levels of proinflammatory cytokines and myostatin, elevated fibrosis, reduced adenosine monophosphate-activated protein kinase (AMPK) activation, and fetal gene reactivation. Furthermore, recent studies have evidenced that excessive training induced an inflammatory status in the serum, muscle, hypothalamus, and liver, suggesting a pathological condition that could also be detrimental to cardiac tissue. Here, we verified the effects of three running overtraining (OT) models on the molecular parameters related to physiological and pathological cardiac hypertrophy. C57BL/6 mice performed three different OT protocols and were evaluated for molecular parameters related to physiological and pathological cardiac hypertrophy, including immunoblotting, reverse transcription polymerase chain reaction, histology, and immunohistochemistry analyses. In summary, the three OT protocols induced left ventricle (LV) hypertrophy with signs of cardiac fibrosis and negative morphological adaptations. These maladaptations were accompanied by reductions in AMPKalpha (Thr172) phosphorylation, androgen receptor, and GR expressions, as well as by an increase in interleukin-6 expression. Specifically, the downhill running-based OT model reduced the content of some proteins related to the mTOR signaling pathway and upregulated the beta isoform of myosin heavy-chain gene expression, presenting signs of LV pathological hypertrophy development. PMID- 29797564 TI - Stress, Motivation, and the Gut-Brain Axis: A Focus on the Ghrelin System and Alcohol Use Disorder. AB - Since its discovery, the gut hormone, ghrelin, has been implicated in diverse functional roles in the central nervous system. Central and peripheral interactions between ghrelin and other hormones, including the stress-response hormone cortisol, govern complex behavioral responses to external cues and internal states. By acting at ventral tegmental area dopaminergic projections and other areas involved in reward processing, ghrelin can induce both general and directed motivation for rewards, including craving for alcohol and other alcohol seeking behaviors. Stress-induced increases in cortisol seem to increase ghrelin in the periphery, suggesting a pathway by which ghrelin influences how stressful life events trigger motivation for rewards. However, in some states, ghrelin may be protective against the anxiogenic effects of stressors. This critical review brings together a dynamic and growing literature, that is, at times inconsistent, on the relationships between ghrelin, central reward-motivation pathways, and central and peripheral stress responses, with a special focus on its emerging role in the context of alcohol use disorder. PMID- 29797569 TI - Colorimetric protein determination in microalgae (Chlorophyta): association of milling and SDS treatment for total protein extraction. AB - The use of colorimetric methods for protein quantification in microalgae is hindered by their elevated amounts of membrane-embedded intracellular proteins. In this work, the protein content of three species of microalgae was determined by the Lowry method after the cells were dried, ball-milled, and treated with the detergent sodium dodecyl sulfate (SDS). Results demonstrated that the association of milling and SDS treatment resulted in a 3- to 7-fold increase in protein quantification. Milling promoted microalgal disaggregation and cell wall disruption enabling access of the SDS detergent to the microalgal intracellular membrane proteins and their efficient solubilization and quantification. PMID- 29797570 TI - Emergence of uncommon HIV-1 non-B subtypes and circulating recombinant forms and trends in transmission of antiretroviral drug resistance in patients with primary infection during the 2013-2015 period in Marseille, Southeastern France. AB - Primary HIV-1 infections (PHI) with non-B subtypes are increasing in developed countries while transmission of HIV-1 harboring antiretroviral resistance associated mutations (RAMs) remains a concern. This study assessed non-B HIV-1 subtypes and RAMs prevalence among patients with PHI in university hospitals of Marseille, Southeastern France, in 2005-2015 (11 years). HIV-1 sequences were obtained by in-house protocols from 115 patients with PHI, including 38 for the 2013-2015 period. On the basis of the phylogenetic analysis of the reverse transcriptase region, non-B subtypes were identified in 31% of these patients. They included 3 different subtypes (3A, 1C, 4F), 23 circulating recombinant forms (CRFs) (CRF02_AG, best BLAST hits being CRF 36_cpx and CRF30 in 7 and 1 cases, respectively), and 5 unclassified sequences (U). Non-B subtypes proportion increased significantly, particularly in 2011-2013 vs in 2005-2010 (P = .03). CRF02_AG viruses largely predominated in 2005-2013 whereas atypical strains more difficult to classify and undetermined recombinants emerged recently (2014-2015). The prevalence of protease, nucleos(t)ide reverse transcriptase, and first generation nonnucleoside reverse transcriptase inhibitors-associated RAMs were 1.7% (World Health Organization [WHO] list, 2009/2.6% International AIDS Society [IAS] list, 2017), 5.2%/4.3%, and 5.2%/5.2%, respectively. Etravirine/rilpivirine associated RAM (IAS) prevalence was 4.3%. Men who have sex with men (MSM) were more frequently infected with drug-resistant viruses than other patients (26% vs 7%; P = .011). The recent increase of these rare HIV-1 strains and the spread of drug-resistant HIV-1 among MSM in Southeastern France might be considered when implementing prevention strategies and starting therapies. PMID- 29797571 TI - Spheroids from adipose-derived stem cells exhibit an miRNA profile of highly undifferentiated cells. AB - Two-dimensional (2D) cell cultures have been extensively used to investigate stem cell biology, but new insights show that the 2D model may not properly represent the potential of the tissue of origin. Conversely, three-dimensional cultures exhibit protein expression patterns and intercellular junctions that are more representative of their in vivo condition. Multiclonal cells that grow in suspension are defined as "spheroids," and we have previously demonstrated that spheroids from adipose-derived stem cells (S-ASCs) displayed enhanced regenerative capability. With the current study, we further characterized S-ASCs to further understand the molecular mechanisms underlying their stemness properties. Recent studies have shown that microRNAs (miRNAs) are involved in many cellular mechanisms, including stemness maintenance and proliferation, and adipose stem cell differentiation. Most studies have been conducted to identify a specific miRNA profile on adherent adipose stem cells, although little is still known about S-ASCs. In this study, we investigate for the first time the miRNA expression pattern in S-ASCs compared to that of ASCs, demonstrating that cell lines cultured in suspension show a typical miRNA expression profile that is closer to the one reported in induced pluripotent stem cells. Moreover, we have analyzed miRNAs that are specifically involved in two distinct moments of each differentiation, namely early and late stages of osteogenic, adipogenic, and chondrogenic lineages during long-term in vitro culture. The data reported in the current study suggest that S-ASCs have superior stemness features than the ASCs and they represent the true upstream stem cell fraction present in adipose tissue, relegating their adherent counterparts. PMID- 29797572 TI - Chronic phosphodiesterase type 5 inhibition has beneficial effects on subcutaneous adipose tissue plasticity in type 2 diabetic mice. AB - Different adipose tissue (AT) depots are associated with multiple metabolic risks. Phosphodiesterase type 5 (PDE5) is involved in adipocyte physiology and PDE5 inhibition may affect adipogenesis and ameliorate white AT quality. The aim of this study is to investigate the distribution of AT and the composition of the stroma-vascular fraction (SVF) of subcutaneous AT (SAT) in type 2 diabetic mice after prolonged treatment with a PDE5 inhibitor, Sildenafil. 18 db/db mice were treated with Sildenafil or vehicle for 12 weeks. AT distribution was monitored and SAT was processed for isolation of SVF by flow cytometry. Sildenafil induced an overall reduction in AT, mainly in visceral AT (VAT), compared with SAT. In Sildenafil-treated mice, the mean change in body weight from baseline positively correlated with VAT, but not with SAT. Characterization of SVF of SAT showed an increase in the frequency of M2 macrophages and endothelial cells in treated mice. Sildenafil improved the maintenance of SAT homeostasis and distribution. PMID- 29797573 TI - Mcl-1 targeting could be an intriguing perspective to cure cancer. AB - The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy is apoptosis. Mcl-1 is a potent oncogene that is regulated at the transcriptional, posttranscriptional, and posttranslational levels. Mcl-1 is a short-lived protein that, in the NH2 terminal region, contains sites for posttranslational regulation that can lead to proteasomal degradation. The USP9X Mcl-1 deubiquitinase regulates Mcl-1 and the levels of these two proteins are strongly correlated. Mcl-1 has three splicing variants (the antiapoptotic protein Mcl-1L and the proapoptotic proteins Mcl-1S and Mcl-1ES), each contributing toward apoptosis regulation. In cancers responsible for the most deaths in the world, the presence of Mcl-1 is associated with malignant cell growth and evasion of apoptosis. Mcl-1 is also one of the key regulators of cancer stem cells' self-renewal that contributes to tumor survival. A great number of indirect and selective Mcl-1 inhibitors have been produced and some of these have shown efficacy in several clinical trials. Thus, therapeutic manipulation of Mcl-1 can be a useful strategy to combat cancer. PMID- 29797574 TI - Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired. AB - Bone marrow mesenchymal stem cells (BM-MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM-MSCs is currently unknown. Here, we assessed how obesity affects the function of BM MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM-MSCs were obtained from healthy donors with a normal (<25) or high (>30) body mass index (BMI). High-BMI BM-MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM-MSC donors for regenerative medicine purposes and that application of high-BMI BM-MSCs with TUDCA or 4-PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed. PMID- 29797575 TI - The promise of stem cell markers in the diagnosis and therapy of epithelial dysplasia and oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer. Epithelial dysplasia is often initiated in the cells and cell nuclei adjacent to the epithelial cell membrane. Reduced cell-cell adhesions enable cancer cells to detach from the tumor and disseminate to other organs. The mutations in epithelial dysplasia markers such as E-cadherin and epithelial cell adhesion molecules (CD326) can lead to proliferation, growth and survival of the tumor cells and persistence of numerous malignancies that play a key role in epithelial dysplasia of OSCC. Accordingly, these genes can be considered prognostic markers or potential therapeutic targets for the tailored management of patients with OSCC. The gene expression profile of OSCC stem cells indicates a differential pattern that facilitates establishing a cell signature. Owing to the highly tumorigenic behavior of cancer stem cells and the role of these cells in tumor differentiation, treatment resistance, relapse, and metastasis, we reviewed the role of stem cell markers in epithelial dysplasia and OSCC. PMID- 29797576 TI - Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti inflammatory, and immunostimulatory activities in 4T1 tumor-bearing Balb/c mice. AB - Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary-tumor-bearing mice. Two-hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor-bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNgamma) was augmented in both healthy and tumor-bearing animals (P < 0.01), and IL-4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki-67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF-kappaB were significantly decreased in tumors from UMB-treated animals (P < 0.001), whereas E-Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB-administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells. PMID- 29797577 TI - The immunomodulatory effects of adipose-derived mesenchymal stem cells and mesenchymal stem cells-conditioned medium in chronic colitis. AB - Inflammatory bowel disease (IBD) as a chronic recurrent disorder is characterized by mucosal immune response dysregulation, which is more prevalent in the youth. Adipose-derived mesenchymal stem cells (ADMSCs) are the multipotent cells that can be effective in immune response regulation via cell-cell interaction and their secretions. In this study, the effects of ADMSCs and mesenchymal stem cell conditioned medium (MSC-CM) were evaluated on dextran sulfate sodium (DSS) induced colitis in mice. Chronic colitis was induced in female C57BL/6 mice using 2% DSS in drinking water for three cycles; there were 4 days of DSS-water administration that was followed by 7 days of DSS-free water, in a cycle. ADMSCs, 106 cells per mouse, were injected intraperitoneally (IP), whereas the MSC-CM injection was also performed six times from the last day of DSS in Cycle 1. Clinical symptoms were recorded daily. The colon pathological changes, cytokine levels, and regulatory T (Treg) cell percentages were then analyzed. After receiving ADMSCs and MSC-CM in colitis mice, the clinical symptoms and disease activity index were improved and the survival rate was increased. The histopathological examination also showed tissue healing in comparison with the nontreated group. In addition, the increased level of transforming growth factor beta, increased percentage of Treg cells, increased level of interleukin (IL)-10, and decreased level of IL-17 were observed after the treatment. This study showed the regulatory effects of ADMSCs and MSC-CM on inflammatory responses. Therefore, the use of ADMSCs and MSC-CM can be introduced as a new and effective therapeutic approach for patients with colitis. PMID- 29797578 TI - Respiratory muscle training for cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 17 April 2018.A hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases up until 07 May 2018. SELECTION CRITERIA: Randomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Review authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system MAIN RESULTS: Authors identified 19 studies, of which nine studies with 202 participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the nine included studies were published as abstracts only and lacking concise details, thus limiting the information available. Seven studies were parallel studies and two of a cross-over design. Respiratory muscle training interventions varied dramatically, with frequency, intensity and duration ranging from thrice weekly to twice daily, 20% to 80% of maximal effort, and 10 to 30 minutes, respectively. Participant numbers ranged from 11 to 39 participants in the included studies; five studies were in adults only and four in a combination of children and adults.No significant improvement was reported in the primary outcome of pulmonary function (forced expiratory volume in one second and forced vital capacity) (very low-quality evidence). Although no change was reported in exercise capacity as assessed by the maximum rate of oxygen use, a 10% improvement in exercise duration was found when working at 60% of maximal effort in one study (n = 20) (very low-quality evidence). In a further study (n = 18), when working at 80% of maximal effort, health-related quality of life improved in the mastery and emotion domains (very low-quality evidence). With regards to the review's secondary outcomes, one study (n = 11) found a significant change in intramural pressure, functional residual capacity and maximal inspiratory pressure following training (low-quality evidence). A further study (n = 22) reported that respiratory muscle endurance was significantly longer in the training group (P < 0.01). No studies reported on any other secondary outcomes. Meta-analyses could not be performed due to a lack of consistency and insufficient detail in reported outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence to suggest whether this intervention is beneficial or not. Healthcare practitioners should consider the use of respiratory muscle training on a case-by-case basis. Further research of reputable methodological quality is needed to determine the effectiveness of respiratory muscle training in people with cystic fibrosis. Researchers should consider the following clinical outcomes in future studies; respiratory muscle function, pulmonary function, exercise capacity, hospital admissions, and health-related quality of life. Sensory perceptual changes, such as respiratory effort sensation (e.g. rating of perceived breathlessness) and peripheral effort sensation (e.g. rating of perceived exertion) may also help to elucidate mechanisms underpinning the effectiveness of respiratory muscle training. PMID- 29797579 TI - Consequences of secondary nectar robbing for male components of plant reproduction. AB - PREMISE OF THE STUDY: Organisms engage in multiple species interactions simultaneously. While pollination studies generally focus on plants and pollinators exclusively, secondary robbing, a behavior that requires other species (primary robbers) to first create access holes in corollas, is common. It has been shown that secondary robbing can reduce plants' female fitness; however, we lack knowledge about its impact on male plant fitness. METHODS: We experimentally simulated primary and secondary robbing in the monocarpic perennial Ipomopsis aggregata (Polemoniaceae), quantifying indirect effects on pollinator-mediated pollen (dye) donation. We also assessed whether continual nectar removal via the floral opening has similar effects on hummingbird pollinator behavior as continual secondary robbing through robber holes. KEY RESULTS: We found no significant indirect effects of secondary robbing on a component of Ipomopsis male fitness. Although robbing did reduce pollen (dye) donation due to avoidance of robbed plants by pollinating hummingbirds, pollen donation did not differ between the two robbing treatments. The effects of secondary robbing on hummingbird behavior resembled effects of chronic nectar removal by pollinators. Our results indicate that hummingbird pollinators may use a combination of cues, including cues given by the presence or absence of nectar, to make foraging decisions. CONCLUSIONS: Combined with prior research, this study suggests that secondary robbing is less costly to a component of male fitness than to female fitness in Ipomopsis, broadening our knowledge of the overall costs of mutualism exploitation to total plant fitness. PMID- 29797580 TI - Zafirlukast promotes insulin secretion by increasing calcium influx through L type calcium channels. AB - The zafirlukast has been reported to be anti-inflammatory and widely used to alleviate the symptoms of asthma. However, its influence on insulin secretion in pancreatic beta-cells has not been investigated. Herein, we examined the effects of zafirlukast on insulin secretion and the potential underlying mechanisms. Among the cysteinyl leukotriene receptor 1 antagonists, zafirlukast, pranlukast, and montelukast, only zafirlukast enhanced insulin secretion in a concentration dependent manner in both low and high glucose conditions and elevated the level of [Ca2+ ]i , further activating Ca2+ /calmodulin-dependent protein kinase II (CaMKII), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) signaling. These effects were nearly abolished by the L-type Ca2+ channel antagonist nifedipine, while treatment with thapsigargin, a sarco/endoplasmic reticulum Ca2+ ATPase inhibitor, did not have the same effect, suggesting that zafirlukast primarily induces the entry of extracellular Ca2+ rather than intracellular Ca2+ from the endoplasmic reticulum. Zafirlukast treatment resulting in a significant drop in glucose levels and increased insulin secretion in C57BL/6J mice. These findings will contribute to an improved understanding of the side effects of zafirlukast and potential candidate for a therapeutic intervention in diabetes. PMID- 29797581 TI - The power of meaning: the quest for an existential roadmap. AB - Where can we turn to find the story of our lives-an existential roadmap that explains where we have come from, why we are here, and where we are headed? Must each of us discover meaning within the context of our individual lives, or are there universal sources of meaning that we can all access? Is there any relationship between living a meaningful life and the quality of our health and well-being? And how can we find meaning in the face of adversity and suffering? Neurologist Jay Lombard, philosophers Massimo Pigliucci and Michael Ruse, and author Emily Esfahani Smith shed light on these perennial questions in conversation with Steve Paulson, executive producer and host of To the Best of Our Knowledge. PMID- 29797582 TI - Milling-Induced Synthesis of BiOCl1-x Brx Solid Solution and Their Adsorptive and Photocatalytic Performance. AB - CH3 COO(BiO) (denoted as BiOAc) is one of the most easily obtained bismuth compounds and was for the first time proposed by our group as an effective UV light photocatalyst. Herein, BiOCl1- x Brx (x refers to the feeding atomic ratio) were obtained using a facile solid state milling and subsequent water washing. More importantly, all of the as-prepared BiOCl1- x Brx possessed better visible light photocatalytic activity to the corresponding ones obtained by previously reported solution route. Especially at an optimal x value of 0.5, the solid solution showed the highest photodegradation efficiency (~100%) for rhodamine B (RhB) with a concentration of 30 mg L-1 , whereas the degradation efficiency was only 63% over that obtained by solution route. Furthermore, the as-prepared BiOCl0.5 Br0.5 also exhibited excellent photodegradation activity for malachite green (MG). The superior photocatalytic performance of the as-prepared BiOCl0.5 Br0.5 could be attributed to its thinner sheetlike structures and highly exposed (001) facets, which enable effective separation of the photogenerated electrons and holes along the [001] direction. In addition, the as-prepared BiOCl0.5 Br0.5 revealed dramatic adsorption capacity for cationic dyes like MG, RhB and methylene violet (MV), as well as anion (Cr2 O7 )2- owing to electrostatic interaction between cationic dyes and negatively charged surface of BiOCl0.5 Br0.5 , and positively charged surface in K2 Cr2 O7 solution (pH ~ 3). PMID- 29797583 TI - Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5/3-D24-GM-CSF) in peritoneal mesothelioma mouse model. AB - Oncolytic adenoviral immunotherapy activates the innate immune system with subsequent induction of adaptive tumor-specific immune responses to fight cancer. Hence, oncolytic viruses do not only eradicate cancer cells by direct lysis, but also generate antitumor immune response, allowing for long-lasting cancer control and tumor reduction. Their therapeutic effect can be further enhanced by arming the oncolytic adenovirus with costimulatory transgenes and/or coadministration with other antitumor therapies. ONCOS-102 has already been found to be well tolerated and efficacious against some types of treatment-refractory tumors, including mesothelin-positive ovarian cancer (NCT01598129). It induced local and systemic CD8+ T-cell immunity and upregulated programmed death ligand 1. These results strongly advocate the use of ONCOS-102 in combination with other therapeutic strategies in advanced and refractory tumors, especially those expressing the mesothelin antigen. The in vivo work presented herein describes the ability of the oncolytic adenovirus ONCOS-102 to induce mesothelin-specific T cells after the administration of the virus in bagg albino (BALB/c) mice with mesothelin-positive tumors. We also demonstrate the effectiveness of the interferon-gamma the enzyme-linked immunospot (ELISPOT) assay to detect the induction of T-cells recognizing mesothelin, hexon, and E1A antigens in ONCOS-102 treated mesothelioma-bearing BALB/c mice. Thus, the ELISPOT assay could be useful to monitor the progress of therapy with ONCOS-102. PMID- 29797584 TI - Healthcare Costs for Insured Older U.S. Adults with Hearing Loss. AB - OBJECTIVES: To measure 18-month healthcare cost difference attributable to hearing loss (HL) in older adults. DESIGN: Matched cohort. SETTING: Retrospective analysis of administrative healthcare bills of insured older Americans. PARTICIPANTS: Older U.S. adults with health insurance in 3 cohorts matched based on HL diagnosis using propensity score methods (N=904,750). MEASUREMENTS: Comparison groups were defined as those with and without HL diagnosis using International Classification of Diseases, Ninth Revision, diagnosis codes from billing records. Outcomes measured include 18-month total healthcare payments and healthcare payments broken down according to payment type (inpatient, outpatient, prescription, hearing services). Three comparison cohorts were examined for these outcomes: individuals covered by Medicare plus supplemental private insurance (Cohort 1, n=782,216), those covered only under Medicare (Cohort 2, n=105,296), and those within the Medicare sample that were dually eligible for Medicare and Medicaid coverage (Subcohort 3, n=17,238). The quality of the propensity score match was examined using standardized differences in means or proportions between all matched covariates, and cost outcomes were analyzed using multiple generalized linear regression models. RESULTS: Fully adjusted models showed significantly higher 18-month healthcare payments for individuals with a diagnosis of HL without indication of use of hearing services than in those without a HL diagnosis in the 3 samples (payment differences: $3,587 Cohort 1, $3,779 Cohort 2, $4,657 Subcohort 3; all p<.001). Payment differences were also found between individuals with HL and indications of hearing services and those without HL. CONCLUSION: We observed more than 20% higher total healthcare payments over 18 months for a group of insured individuals with HL regardless of insurance type or hearing services use, indicating that negative health-related effects of HL may increase healthcare use unrelated to HL. Thus, clinical care to ameliorate HL may improve overall health. PMID- 29797585 TI - The effects of music-supported therapy on motor, cognitive, and psychosocial functions in chronic stroke. AB - Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty-eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10-week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke-McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well-being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community-dwelling chronic-stage survivors. PMID- 29797586 TI - Determinants of the presence of human papillomaviruses in the anal canal of Russian men. AB - Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high-risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]-negative and 27 HIV positive, aged 18-67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV-positivity in anal samples was common for 332 HIV-negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV-positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV-negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection. PMID- 29797587 TI - Effects of combined magnetic fields on bacteria Rhodospirillum rubrum VKM B-1621. AB - Bacteria are the simplest model of living organisms and thus are a convenient object for magnetobiological research. This paper describes some effects of combined magnetic fields (CMFs) on the bacterium Rhodospirillum rubrum strain VKM B-1621, which is not a pathogen but was selected due to its wide spectrum of growth abilities. The authors chose magnetic field-resonant phosphorus and iron (Fe3+ ) because P-containing biochemical compounds (standard abbreviations PP1 , AMP, ADP, ATP) provide energy flows in bacteria while iron could take part in formation of magnetosensitive intracellular inclusions. CMFs were produced by interaction of a geomagnetic field (VDS ) and an alternating electromagnetic field (VAS ), which were similar in their intensities. Their magnetic characteristics were as follows: (CMF-1) VDC = 46.80 uT, VAS = 86.11 uT, f = 807.0 Hz; (CMF-2) VDC = 46.80 uT, VAS = 86.11 uT, f = 38.3 Hz; that is, the frequencies of applied alternating electromagnetic fields coincided with cyclotron frequencies of phosphorus or ferric ions, respectively. The blank variants were exposed to the geomagnetic field. The CMFs increased bacterial consumption of dissolved iron as measured by residual concentrations of iron in the medium (P > 99%). An increase of bacterial nitrate reduction in the CMFs was statistically insignificant (P > 90%) when measured by residual concentrations of nitrate. Application of CMFs can influence bacterial activity and metabolism. Bioelectromagnetics. 2018;39:485-490, 2018. (c) 2018 Wiley Periodicals, Inc. PMID- 29797588 TI - Effects of home-based exergaming on child social cognition and subsequent prediction of behavior. AB - The use of exergames may be one viable way to increase child physical activity, but investigation of its effects on motivation over time and prediction of adherence have seen little research attention. The purpose of this study was to compare the effect of two cycling exergame interventions (single-player, multi player) among children aged 9-12 years on motivational variables (theory of planned behavior) and to explore whether these variables could predict objective assessment of playtime across 6 weeks. Sixty-nine insufficiently active children were recruited through advertisements within the community/schools and randomized to either the single play condition (n = 30) or multi-player condition (n = 39). Exergaming use was recorded objectively via game logs and motivational variables were assessed after a familiarization session, at 2 weeks, and at 4 weeks. Participants played the exergames M = 133.45 (SD = 81.27) minutes in week 1 to M = 77.23 (SD = 84.09) minutes in week 6. The two exergame conditions did not result in differences among theory of planned behavior variables (P > .05). Mean levels of these constructs declined across the first 4 weeks (P < .05), with the exception of injunctive norm. Positive bivariate associations (P < .05) between game play and perceived control (0-6 weeks), and intention (weeks 3-4 and weeks 5 6) were identified, but only affective attitude (assessed at week 2) predicted (P < .05) game play (3-4 weeks) in a multivariate examination of the theory of planned behavior model. The results demonstrate that social cognitive motives wane across time when exposed to repeated exergame play. PMID- 29797589 TI - Sequence variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China. AB - The BamHI A rightward frame 1 (BARF1) gene of the Epstein-Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV-associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non-endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95-8 and V29A) and 2 B95-8 subtypes (B95-8t165545c and B95-8P ) were classified. For Chinese isolates, the B95-8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95-8t165545c subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95-8t165545c subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95-8P subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95 8t165545c subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95-8t165545c subtype in NPC cases, without biological or pathogenic implications. PMID- 29797590 TI - Specific detection of form IA RubisCO genes in chemoautotrophic bacteria. AB - The analysis of RubisCO genes is a highly useful instrument to explore the diversity of chemoautotrophic bacteria using the Calvin-Benson-Bassham cycle for CO2 fixation. However, because of the wide taxonomic distribution of phylogenetically related RubisCO forms, environmental studies targeting chemoautotrophs are hampered in habitats dominated by phototrophs. Here, we report the development of a gene marker that specifically detects form IA RubisCO genes in bacteria, excluding photoautotrophic representatives. The high specificity of the PCR assay was confirmed by sequence analysis of DNA obtained from the photic zone of six lakes, were chemoautotrophs are outnumbered by Cyanobacteria also using form IA RubisCO for CO2 assimilation. PMID- 29797591 TI - Chromatographic behavior of new deazapurine ribonucleosides in hydrophilic interaction liquid chromatography. AB - The chromatographic behavior of new biogenic purine nucleosides in hydrophilic interaction liquid chromatography was examined on three different stationary phases, namely bare silica, and amide- and cyclofructan-based stationary phases. The effects of buffer concentration, pH and acetonitrile-to-aqueous-part ratio in the mobile phase on retention and peak shape were assessed. The retention coefficients and peak symmetry values substantially differed with respect to analytes' structures, stationary phase properties and mobile phase composition. The bare silica column was unsuitable for these compounds under the chromatographic conditions tested due to very broad and asymmetrical peaks. Furthermore, the cyclofructan-based stationary phase provided almost Gaussian peak shapes of all deazapurine nucleosides under most conditions tested. Therefore, the cyclofructan-based stationary phase is the most suitable choice for the chromatographic analysis of nucleosides. PMID- 29797593 TI - Chain dynamics of human dermis by Thermostimulated currents: A tool for new markers of aging. AB - BACKGROUND/PURPOSE: The purpose of this clinical study was to identify dielectric markers to complete a previous thermal and vibrational study on the molecular and organizational changes in human dermis during intrinsic and extrinsic aging. METHODS: Sun-exposed and non-exposed skin biopsies were collected from 28 women devised in two groups (20-30 and >=60 years old). The dielectric relaxation modes associated with localized and delocalized dynamics in the fresh and dehydrated state were determined by the Thermostimulated currents technique (TSC). RESULTS: Intrinsic and extrinsic aging induced significant evolution of some of the dielectric parameters of localized and delocalized dynamics of human skin. With photo-aging, freezable water forms a segregated phase in dermis and its dynamics is close to free water, what evidences the major role of extrinsic aging on water organization in human skin. Moreover, TSC indicators highlight the restriction of localized mobility with intrinsic aging due to glycation, and the cumulative effect of chronological aging and photo-exposition on the molecular mobility of the main structural proteins of the dermis at the mesoscopic scale. CONCLUSION: TSC is a well-suited technique to scan the molecular mobility of human skin. It can be uses as a relevant complement of vibrational and thermal characterization to follow human skin modifications with intrinsic and extrinsic aging. PMID- 29797592 TI - Scheduling of eccentric lower limb injury prevention exercises during the soccer micro-cycle: Which day of the week? AB - Scheduling eccentric-based injury prevention programs (IPP) during the common 6 day micro-cycle in soccer is challenged by recovery and tapering phases. This study profiled muscle damage, neuromuscular performance, and perceptual responses to a lower limb eccentric-based IPP administered 1 (MD+1) vs 3 days (MD+3) postmatch. A total of 18 semi-professional players were monitored daily during 3 in-season 6-day micro-cycles, including weekly competitive fixtures. Capillary creatine kinase concentration (CK), posterior lower limb isometric peak force (PF), counter-movement jump (CMJ) performance, and muscle soreness were assessed 24 hours prior to match-day (baseline), and every 24 hours up to 120 hours postmatch. The IPP consisted of lunges, single stiff leg dead-lifts, single leg squats, and Nordic hamstring exercises. Performing the IPP on MD+1 attenuated the decline in CK normally observed following match play (CON: 142%; MD+3: 166%; small differences). When IPP was delivered on MD+3, CK was higher vs CON and MD+1 trials on both MD+4 (MD+3: 260%; CON: 146%; MD+1: 151%; moderate differences) and MD+5 (MD+3: 209%; CON: 125%; MD+1: 127%; small differences). Soreness ratings were not exacerbated when the IPP was delivered on MD+1, but when prescribed on MD+3, hamstring soreness ratings remained higher on MD+4 and MD+5 (small differences). No between-trial differences were observed for PF and CMJ. Administering the IPP in the middle of the micro-cycle (MD+3) increased measures of muscle damage and soreness, which remained elevated on the day prior to the next match (MD+5). Accordingly, IPP should be scheduled early in the micro-cycle, to avoid compromising preparation for the following match. PMID- 29797595 TI - No further improvement in pregnancy-related outcomes in the offspring of mothers with pre-gestational diabetes in Bavaria, Germany, between 2001 and 2016. AB - AIMS: To investigate whether there has been further improvement in the risk of adverse outcomes in pregnancies in women with diabetes during 2008-2016 in Bavaria, Germany. METHODS: Using cross-sectional data on all 1716 170 deliveries in Bavarian hospitals between 2001 and 2016, we assessed the risks of stillbirth, early neonatal death, preterm delivery, large for gestational age, malformations, low Apgar score and low umbilical cord pH by maternal group with diabetes (gestational, pre-gestational, or none) separately for 2001-2007 and 2008-2016. We also investigated the associations of specific risk factors such as maternal smoking with respect to early mortality and malformations in each group with diabetes during 2008-2016. RESULTS: No further reduction in the risk for any adverse outcome in mothers with pre-gestational diabetes and their offspring during 2008-2016 was observed. Maternal smoking, multiple delivery and substandard antenatal care were the strongest additional predictors of both early perinatal mortality and malformations for mothers with pre-gestational diabetes. The respective risks were lower and also decreased over time for mothers with gestational diabetes. CONCLUSIONS: No significant improvement has been achieved in the management of pregnancies affected by pre-gestational diabetes during the last decade. The apparent risk reductions in women with gestational diabetes may partly be due to a change in diagnostic criteria over time. Women with pre gestational diabetes who smoke, carry more than one child, or are not regularly seen during pregnancy, may need particular attention. PMID- 29797594 TI - Genome-wide analysis reveals that altered methylation in specific CpG loci is associated with childhood obesity. AB - Over the past decades, the epidemic of childhood obesity has greatly increased, and it has recently become a global public health concern. Methylation, serving as a crucial regulator of the gene-environment interaction, has exhibited a strong association with obesity. In this study, we aimed to evaluate the relationship between DNA methylation and childhood obesity, and further uncover the potential association of aberrantly methylated genes with obesity. DNA samples of peripheral blood leukocytes from three obese subjects (mean BMI: 21.67) and 4 age/sex matched controls (mean BMI: 14.92) were subjected to Infinium Human Methylation 450 Bead Array analysis. A total of more than 4 85 000 methylation sites were identified across the genome, and 226 methylated CpGs (DMCpGs) were differentially methylated between these two groups. Subsequent Gene Ontology (GO) and KEGG Pathway analyses showed that these DMCpGs were mainly engaged in immunity and lipoprotein metabolism, indicating their physiological significance. Further verification of the candidate CpG sites within the HDAC4, RAX2, APOA5, CES1, and SLC25A20 gene loci, were performed using bisulfite sequencing PCR (BSP) in a cohort of 42 controls and 39 obese cases. The results revealed that methylation levels within HDAC4 and RAX2 loci were positively associated with obesity, while the methylation levels of loci within APOA5 and CES1 loci were negatively correlated with obesity. Thus, alterations in methylation of CpG sites of specific genes may contribute to childhood obesity, which provide novel insights into the aetiology of obesity. PMID- 29797596 TI - The interface between the EGF1 and EGF2 domains is critical in integrin affinity regulation. AB - It has been proposed that integrins adopt a bent, closed conformation with low ligand binding capability at resting state and switch into an extended, open conformation upon activation or interacting with extracellular matrix (ECM) ligand. In this study, we addressed how integrin conformational change at the beta genu affects ligand binding and signaling. We discovered that swapping of the beta3 epidermal growth factor-like (EGF) domain 1 and 2 with that of beta8 greatly promoted ligand binding in beta3 beta8 chimeras. Sequence alignment indicated that beta8 integrin uniquely lacks the interface between the EGF1 and 2. Disrupting this interface of the beta3 integrin increased integrin ligand binding. Furthermore, the interface is critical for integrin affinity regulation but not downstream outside-in signaling. PMID- 29797597 TI - Synthesis, evaluation, and molecular docking studies of aryl urea-triazole-based derivatives as anti-urease agents. AB - Considering the importance of urease inhibitors in the treatment of ureolytic bacterial infections, in this work, the synthesis of novel, aryl urea-triazole based derivatives as effective urease inhibitors is described. Dichloro substituted derivative 4o, with IC50 = 22.81 +/- 0.05 MUM, is found to be the most potent urease inhibitor, determined by Berthelot colorimetric assay. Docking studies were also carried out for compound 4o to confirm the effective interactions with the urease active site. PMID- 29797599 TI - Expression of microRNAs and IRAK1 pathway genes are altered in gastric cancer patients with Helicobacter pylori infection. AB - Gastric cancer (GC) is among the most common cancer types in the world and one of the most lethal gastrointestinal cancers. MicroRNAs (miRNAs) can be of great importance in the early detection of GC. This study aimed to investigate some miRNAs and the genes involved in IRAK1 pathways in the serum of GC patients with Helicobacter pylori (H. pylori) infections compared to the control group. Total RNA was extracted from the serum of GC patients with H. pylori infection and healthy volunteers. The expression levels of miRNAs and the genes were assessed using Real time RT-PCR with specific primers. Our data showed that miR-146, miR 375, and Let-7 were down-regulated and miR-19 and miR-21 were up-regulated in GC patients with H. pylori infection. Other genes involved in the pathways such as RAS, MYC, NFKB, JUN, TRAF6, and IRAK4 were overexpressed; while the expression of PTEN gene was decreased compared to the control group. Expression of miRNAs and IRAK1 pathway genes are altered in patients with GC and H. pylori infection. This suggests a potential role for the above-mentioned miRNAs and genes in the diagnosis of GC. PMID- 29797598 TI - Physiological changes in the adenosine deaminase activity, antioxidant and inflammatory parameters in pregnant cows and at post-partum. AB - The aim of this study was to evaluate the behaviour of adenosine deaminase (ADA) activity, as well as its participation in the immunomodulation of pregnant cows. Thus, sixteen cows were divided into two groups (A and B): the group A was composed by cows not pregnant (n = 8), while the group B was composed by pregnant cows (n = 8). Serum levels of interleukin-10 (IL-10), IL-6, tumour necrosis factor alpha (TNF-alpha), reactive oxygen species (ROS) and C-reactive protein (CRP), as well as ADA and glutathione S-transferase (GST) activities, were measured on five sampling times (3, 5, 7 and 8 months of gestation, and soon after calving). Serum ADA activity was similar throughout the experiment in the cows belonging to the group A, but its activity increased during the experiment in cows from the group B, that is it was lower in the third and fifth months of pregnancy, and higher on months 7, 8 and after calving when compared to the group A. TNF-alpha and IL-6 serum levels were lower in pregnant cows compared to non pregnant animals; however, they significantly increased after calving. Serum levels of IL-10 increased after 8 months of gestation, but it reduced after calving when compared to the group A, while CRP increased on month 8 of gestation and after calving compared to the group A. Pregnant cows showed lower serum ROS levels on months 3, 5 and 7 of gestation, and higher levels at the post-partum. Serum GST activity was higher on month 5 of gestation in pregnant cows, but it was lower on months 7, 8 and in the post-partum compared to the group A. Based on these evidence, we concluded that ADA activity and the others mediators or inflammatory modulators have important role in the maintenance of cow's gestation due to their immunomodulatory effects. PMID- 29797600 TI - Downregulation of ARID4A and ARID4B promote tumor progression and directly regulated by microRNA-30d in patient with prostate cancer. AB - AT-rich interaction domain 4A (ARID4A) and AT-rich interaction domain 4B (ARID4B), which are both the AT-rich interaction domain (ARID) family, have been reported to be oncogene or tumor suppressor gene in various human malignances, but there is no involvement about their functions in prostate cancer (PCa). Our previous study has reported that microRNA-30d (miR-30d) expression can predicted poor clinical prognosis in PCa, however, the underlying mechanisms of miR-30d have not been fully described. The aim of our study is to investigate the expression relevance between miR-30d and ARID4A or ARID4B, and examine the clinical significance and biological function of ARID4A and AIRD4B in PCa. In this study, both ARID4A and ARID4B were identified as the target genes of miR 30d. In addition, the mRNA expression of miR-30d in PCa tissues were significantly negative correlated with ARID4A (Pearson correlation coefficient = 0.313, P = 0.001) and ARID4B (Pearson correlation coefficient = -0.349, P < 0.001), while there was a positive correlation between ARID4A and ARID4B (Pearson correlation coefficient = 0.865, P < 0.001). Moreover, both ARID4A and ARID4B were significantly downregulated in PCa tissues with high Gleason scores (P = 0.005, P = 0.033), PSA failure (P = 0.012, P = 0.05) and short biochemical recurrent-free survival (P = 0.033, P = 0.031). Furthermore, the knockout expression of ARID4A and ARID4B promoted PCa cell proliferation, migration and invasion in vitro. In conclusion, our results indicated that ARID4A and ARID4B may serve as tumor suppressor in PCa progression, suggesting that they might be the potential therapeutic targets in prostate cancer. PMID- 29797601 TI - Scutellaria baicalensis targets the hypoxia-inducible factor-1alpha and enhances cisplatin efficacy in ovarian cancer. AB - Hypoxia-inducible factor-1alpha (HIF-1alpha) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1alpha may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1alpha expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF 1alpha expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1alpha levels similar to cells treated with SB. Furthermore, SB induced HIF-1alpha inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor) reduced HIF-1alpha expression comparable to SB-treated cells. SB potentiated the anti-growth effects of cisplatin on OC cells by attenuating the expression of HIF-1alpha, ABCG1, and ABCG2. Taken together, the findings suggest that targeting HIF-1alpha with SB could be an effective treatment strategy for cancer and SB can improve the sensitivity of cancer cells to cisplatin, which is a major challenge in therapy for ovarian tumors. PMID- 29797603 TI - Gender and Publishing in Nursing: a secondary analysis of h-index ranking tables. AB - AIMS: To analyse published ranking tables on academics' h-index scores to establish whether male nursing academics are disproportionately represented in these tables compared with their representation across the whole profession. BACKGROUND: Previous studies have identified a disproportionate representation of UK male nursing academics in publishing in comparison to their US counterparts. DESIGN: Secondary statistical analysis, which involved comparative correlation of proportions. METHODS: Four papers from the UK, Canada and Australia containing h index ranking tables and published between 2010-2017, were re-analysed in June 2017 to identify authors' sex. Pearson's chi-squared test was applied to ascertain whether the number of men included in the tables was statistically proportionate to the number of men on the pertinent national professional register. FINDINGS: There was a disproportionate number of men with high h-index scores in the UK and Canadian data sets, compared with the proportion of men on the pertinent national registers. The number of men in the Australian data set was proportionate with the number of men on the nursing register. There was a disproportionate number of male professors in UK universities. CONCLUSION: The influence of men over nursing publishing in the UK and Canada outweighs their representation across the whole profession. Similarly, in the UK, men's representation in the professoriate is disproportionately great. However, the Australian results suggest that gender inequality is not inevitable and that it is possible to create more egalitarian nursing cultures. This article is protected by copyright. All rights reserved. PMID- 29797602 TI - Gypenoside inhibits RANKL-induced osteoclastogenesis by regulating NF-kappaB, AKT, and MAPK signaling pathways. AB - Gypenoside (GP) is one of the most pharmacologically active components in Gynostemma pentaphyllum and possesses neuroprotective, anticancer, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-osteoarthritis effects. However, the involvement of GP the osteoclast differentiation has not yet been investigated. In the present study, we examined the effect of GP on receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast formation. Our results demonstrated that GP significantly inhibited the formation of osteoclast, as well as suppressed the expression of osteoclastogenesis-related marker proteins in RANKL-stimulated bone marrow macrophages (BMMs). For molecular mechanisms, GP inhibited RANKL-induced NF-kappaB and MAPK activation and AKT phosphorylation in BMMs. Collectively, these findings suggest that GP inhibits RANKL-induced osteoclastogenesis via regulating NF-kappaB, AKT, and MAPK signaling pathways. Therefore, GP may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. PMID- 29797604 TI - Structure, molecular dynamics simulation, and docking studies of Dictyostelium discoideum and human STRAPs. AB - The Serine Threonine kinase Receptor Associated Protein (STRAP) is a WD40 containing protein that provides a platform for protein interactions during cell proliferation and development. Overexpression and misregulation of STRAP contributes to various carcinomas that are now recognized as therapeutic targets especially for colorectal and lung cancers. The present study was undertaken to find an effective drug against this molecule using a simple system like Dictyostelium discoideum; which shares close homology to humans. Using techniques like structural modeling, molecular dynamics (MD) simulation and molecular docking, we found similar structure and dynamic behaviors in both, except for the presence of dissimilar numbers of beta-sheets and loop segments. We identified a novel and potential drug targeted to STRAP. The results obtained allow us to use Dictyostelium as a model system for further in vivo studies. Finally, the results of protein-protein interactions using molecular docking and essential dynamics studies show STRAP to participate in TGF-beta signaling in humans. Further, we show some structural units that govern the interaction of TGFbeta-RI with STRAP and Smad7 proteins in TGF-beta signaling pathway. In conclusion, we propose that D. discoideum can be used for enhancing our knowledge about STRAP protein. PMID- 29797605 TI - beta-adrenergic receptors and cardiac progenitor cell biology: What is the real connection? AB - Resident cardiac progenitor cells (CPCs) isolated from small animal models may not always be representative of their human counterparts, especially when significant differences in isolation protocols are considered. Nonetheless, multiple evidences support an important role of beta-adrenergic signaling in human CPC survival and commitment, which will need appropriate consideration for future developments of human CPCs as regenerative medicine tools. PMID- 29797606 TI - Prevalence of Usutu and West Nile virus antibodies in human sera, Modena, Italy, 2012. AB - A collection of 3069 human sera collected in the area of the municipality of Modena, Emilia Romagna, Italy, was retrospectively investigated for specific antibodies against Usutu (USUV) and West Nile viruses (WNV). All the samples resulting positive using a preliminary screening test were analyzed with the plaque reduction neutralization test. Overall, 24 sera were confirmed as positive for USUV (0.78%) and 13 for WNV (0.42%). The results suggest that in 2012, USUV was circulating more than WNV in North-eastern Italy. PMID- 29797608 TI - Uncertainty analysis and robust areas of high and low modeled human impact on the global oceans. AB - Increasing anthropogenic pressure on marine ecosystems from fishing, pollution, climate change, and other sources is a big concern in marine conservation. Scientists have thus developed spatial models to map cumulative human impacts on marine ecosystems. However, these models are based on many assumptions and incorporate data that suffer from substantial incompleteness and inaccuracies. Rather than using a single model, we used Monte Carlo simulations to identify which parts of the oceans are subject to the most and least impact from anthropogenic stressors under 7 simulated sources of uncertainty (factors: e.g., missing stressor data and assuming linear ecosystem responses to stress). Most maps agreed that high-impact areas were located in the Northeast Atlantic, the eastern Mediterranean, the Caribbean, the continental shelf off northern West Africa, offshore parts of the tropical Atlantic, the Indian Ocean east of Madagascar, parts of East and Southeast Asia, parts of the northwestern Pacific, and many coastal waters. Large low-impact areas were located off Antarctica, in the central Pacific, and in the southern Atlantic. Uncertainty in the broad-scale spatial distribution of modeled human impact was caused by the aggregate effects of several factors, rather than being attributable to a single dominant source. In spite of the identified uncertainty in human-impact maps, they can-at broad spatial scales and in combination with other environmental and socioeconomic information-point to priority areas for research and management. PMID- 29797607 TI - Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands. AB - Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed. PMID- 29797609 TI - HTLV-1 and -2 in a first-time blood donor population in Northeastern Brazil: Prevalence, molecular characterization, and evidence of intrafamilial transmission. AB - Independent epidemiology for respective human T-cell lymphotropic virus (HTLV) types 1 and 2 is little known in blood donors in Brazil, where screening for HTLV 1/2 is mandatory at blood banks, but no testing to confirm/differentiate these viruses. Therefore, this study aims to assess the prevalence of HTLV-1 and -2 in a first-time blood donor population in Northeastern Brazil and to carry out molecular characterization of respective isolates. A cross-sectional study was conducted at the State Blood Bank in Piaui. Samples were screened for anti-HTLV 1/2 by enzyme immunoassay, and reactive samples were confirmed using a line immunoassay and polymerase chain reaction (PCR). Of 37 306 blood donors, 47 were anti-HTLV-1/2 reactive by enzyme immunoassay. After confirmed by line immunoassay, 22 were positive for HTLV-1 (0.59 per 1000; 95% CI: 0.38-0.87), 14 were positive for HTLV-2 (0.37 per 1000; 95% CI: 0.21-0.61), 1 was indeterminate, and the remaining donors were negative. The HTLV-1 infection was also confirmed by PCR in all anti-HTLV-1-positive samples, and sequencing classified these isolates as belonging to the Transcontinental (A) subgroup of the Cosmopolitan (1a) subtype. Of 14 anti-HTLV-2-positive samples, 11 were also PCR positive, which belonged to subtype a (HTLV-2a/c). In addition, 38 family members of 5 HTLV 1- and 3 HTLV-2-infected donors were analyzed. Familial transmission of HTLV-1 and -2 was evidenced in 3 families. In conclusion, in Northeastern Brazil, where HTLV-1 and -2 are endemic, counseling blood donor candidates and their families might play a key role in limiting the spread of these viruses. PMID- 29797610 TI - Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas. AB - BACKGROUND: Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. METHODS: Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. RESULTS: The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease specific and disease-free survival. CONCLUSIONS: These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence. PMID- 29797611 TI - Radical Cation pi-Dimers of Conjugated Oligomers as Molecular Wires: An Analysis Based on Nitronyl Nitroxide Spin Labels. AB - Nitronyl nitroxide (NN)-substituted conjugated oligomers, which were expected to self-associate in biradical cation states, were designed to analyze the capability of pi-dimers as molecular wires. The oligomer moieties were composed of dithienyl-N-methylpyrrole with methoxy substituents at the inner beta-position of thiophene rings (DTP-NN. ) and its propylenedioxythiophene (ProDOT) inserted derivative (DTP-P-NN. ), or two ethylenedioxythiophene (EDOT) and two ProDOT units (E2 P2 -NN. ). Among them, chemical one-electron oxidation gave biradical cations (DTP-P).+ -NN. and (E2 P2 ).+ -NN. that formed pi-dimers (DTP-P-NN. )22+ and (E2 P2 -NN. )22+ in dichloromethane at low temperatures. ESR studies of (DTP P-NN. )22+ and (E2 P2 -NN. )22+ showed the presence of a relatively strong exchange interaction between two NN radicals through the radical cation pi-dimer moieties. DFT calculations supported these experimental results and predicted that exchange interactions between two NN radicals were comparable or stronger than those through covalently linked quaterthiophene. Thus, the conjugated oligomer radical cation pi-dimers acted as efficient molecular wires for electronic communication. PMID- 29797612 TI - Training in transplant infectious diseases: A survey of infectious diseases and transplant infectious diseases fellows in the United States and Canada. AB - BACKGROUND: Infectious diseases (ID) specialists with experience in managing infections in transplant recipients and other immunocompromised hosts are increasingly needed as these fields expand. METHODS: To evaluate experiences and identify trainee-described needs in transplant infectious diseases (TID) training, the American Society of Transplantation, Infectious Diseases Community of Practice (AST IDCOP) surveyed ID fellows across the United States and TID fellows in the United States and Canada and received responses from 203 ID fellows and 13 TID fellows. RESULTS: Among ID fellows, the amount of TID training during ID fellowship was rated between less than ideal and adequate. Reasons cited included limited frequency of didactic activities and limited exposure to transplant patients during training. In particular, ID fellows at low-volume transplantation centers expressed interest in more TID training time, away training opportunities, and specific TID didactics. Educational resources of high interest among trainees were case-based interactive websites, mobile phone applications with TID guidelines, and a centralized collection of relevant articles. Pediatric ID fellows reported lower satisfaction scores with TID training, while TID fellows were overall satisfied or more than satisfied with their training experience. CONCLUSION: Findings from this survey will inform local and national TID educational initiatives. PMID- 29797615 TI - Radiography and ultrasonography of pneumatosis intestinalis in a cat. AB - An adult cat was presented for acute history of vomiting and collapse. Radiographs showed the presence of air within small intestinal walls and arborizing gas patterns within the liver, compatible with pneumatosis intestinalis and presumed portal venous gas, respectively. An abdominal ultrasound the following day was suggestive of gas within the intestinal wall, however, gas within the hepatic vasculature, parenchyma, or biliary tree was not evident. Due to progressive clinical deterioration of the patient, the owners elected humane euthanasia. Necropsy revealed severe necrotizing hemorrhagic enterotyphlocolitis secondary to Clostridium difficile toxin. PMID- 29797614 TI - Comparative Analysis of Markers of Mass Effect after Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Midline shift determined on magnetic resonance imaging (MRI) or computed tomography (CT) images is a well-validated marker of mass effect after large hemispheric infarction and associated with mortality. In this study, we targeted a population with moderately sized strokes. We compared midline shift to other imaging markers and determined their ability to predict long-term outcome. METHODS: MRI scans were studied from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) cohort. Midline shift, acute stroke lesion volume, lesional swelling volume, change in ipsilateral hemisphere volume, the ratio of ipsilateral to contralateral hemisphere volume, and the reduction in lateral ventricle volume were measured. The relationships of these markers with poor outcome (modified Rankin scale score 3-6 at day 90) were assessed. Receiver operating characteristic (ROC) curves were generated to compare the performance of each metric. RESULTS: Of the 71 included patients, 59.2% had a poor outcome that was associated with significantly larger values for midline shift, lesional swelling volume, and ratio of hemisphere volumes. Lesional swelling volume, change in hemisphere volume, ratio of hemisphere volumes, and lateral ventricle displacement were each correlated with midline shift (Spearman r = .60, .49, .61, and -.56, respectively; all P < .0001). ROC curve analysis showed that lesional swelling volume (area under the curve [AUC] = .791) predicted poor outcome better than midline shift (AUC = .682). For predicting mortality, ROC curve analysis showed that these three markers were equivalent. CONCLUSION: The ratio of ipsilateral to contralateral hemisphere volume, baseline lesion volume and lesional swelling volume best predicted poor outcome across a spectrum of stroke sizes. PMID- 29797613 TI - Comparison of intravenous or intravesical cidofovir in the treatment of BK polyomavirus-associated hemorrhagic cystitis following adult allogeneic stem cell transplantation-A systematic review. AB - INTRODUCTION: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical. METHODS: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively. RESULTS: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. CONCLUSION: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile. PMID- 29797617 TI - Reply: Oral anticoagulation and hip fracture risk: a common misconception? PMID- 29797616 TI - Late-phase human herpesvirus 6B reactivation in hematopoietic stem cell transplant recipients. AB - BACKGROUND: We sought to determine whether late-phase human herpesvirus 6B (HHV 6B) infection in hematopoietic stem cell transplant (HSCT) recipients was associated with serious outcomes and mortality. METHODS: The occurrence and course of HHV-6B infection was monitored for at least 60 days after transplant using virus isolation and real-time polymerase chain reaction. Risk factors for late-phase HHV-6B infection were examined, and the propensity score was calculated with significant risk factors. The inverse probability-weighted multivariable logistic regression analysis was performed to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI) for mortality. RESULTS: Late phase HHV-6B infection was observed in 12/89 (13.5%) of the HSCT recipients. Older age (OR: 10.3, 95% CI: 2.1/72.9, P = .0027), hematologic malignancy (OR: 10.3, 95% CI: 1.8/97.1, P = .0063), unrelated donor transplantation (OR: 5.3, 95% CI: 1.1/36.0, P = .0345), and sex-mismatched donor transplantation (OR: 6.3, 95% CI: 1.4/39.5, P = .0149) were identified as risk factors for late-phase HHV-6B infection. Fifteen subjects died (17%). Inverse probability-weighted multivariable logistic model analysis revealed that late-phase HHV-6B infection was an independent risk factor for mortality (OR: 4.2, 95% CI: 1.7/11.0, P = .0012). Among 5 of the fatal cases of late-phase HHV-6B infection, viral infection might be associated with severe clinical manifestations. CONCLUSION: Late-phase HHV-6B infection in HSCT recipients was associated with worse outcomes. The full spectrum of clinical features of the infection has not been fully elucidated, and therefore, recipients with high-risk factors for late-phase HHV-6B infection should be carefully monitored. PMID- 29797619 TI - Multimodality imaging of an azygous continuation of the caudal vena cava in a dog with pulmonary thromboembolic disease. AB - A 5-year-old spayed female English Bulldog was evaluated for acute anorexia, lethargy, respiratory distress, and syncope. Contrast-enhanced computed tomography revealed the vascular malformation of azygous continuation of the caudal vena cava with extensive thrombus formation and pulmonary arterial thromboembolic disease. The patient was hospitalized for supportive treatment and was prescribed long-term clopidogrel therapy. The patient survived to discharge and at last follow-up remained clinically stable. While this vascular malformation has been reported in canines, to the authors' knowledge, this is the first reported case of pulmonary thromboembolic disease in a canine concurrent with this condition. PMID- 29797618 TI - Constitutive plasma membrane monoamine transporter (PMAT, Slc29a4) deficiency subtly affects anxiety-like and coping behaviours. AB - Originally, uptake-mediated termination of monoamine (e.g., serotonin and dopamine) signalling was believed to only occur via high-affinity, low-capacity transporters ("uptake1 ") such as the serotonin or dopamine transporters, respectively. Now, the important contribution of a second low-affinity, high capacity class of biogenic amine transporters has been recognised, particularly in circumstances when uptake1 transporter function is reduced (e.g., antidepressant treatment). Pharmacologic or genetic reductions in uptake1 function can change locomotor, anxiety-like or stress-coping behaviours. Comparable behavioural investigations into reduced low-affinity, high-capacity transporter function are lacking, in part, due to a current dearth of drugs that selectively target particular low-affinity, high-capacity transporters, such as the plasma membrane monoamine transporter. Therefore, the most direct approach involves constitutive genetic knockout of these transporters. Other groups have reported that knockout of the low-affinity, high-capacity organic cation transporters 2 or 3 alters anxiety-like and stress-coping behaviours, but none have assessed behaviours in plasma membrane monoamine transporter knockout mice. Here, we evaluated adult male and female plasma membrane monoamine transporter wild-type, heterozygous and knockout mice in locomotor, anxiety-like and stress coping behavioural tests. A mild enhancement of anxiety-related behaviour was noted in heterozygous mice. Active-coping behaviour was modestly and selectively increased in female knockout mice. These subtle behavioural changes support a supplemental role of plasma membrane monoamine transporter in serotonin and dopamine uptake, and suggest sex differences in transporter function should be examined more closely in future investigations. PMID- 29797621 TI - A randomized controlled evaluation of the tobacco status project, a Facebook intervention for young adults. AB - AIMS: To test the efficacy of the Tobacco Status Project (TSP) Facebook smoking cessation intervention for young adults relative to referral to an on-line program on biochemically verified 7-day abstinence from smoking. DESIGN: Two group parallel randomized controlled trial, comparing TSP (n = 251) to on-line control (n = 249) with follow-up to 12 months. SETTING: On-line, throughout the United States. PARTICIPANTS: Young adult cigarette smokers (mean age 21 years; 73% white, 55% female, 87% daily smokers). INTERVENTIONS AND COMPARATOR: TSP provided private Facebook groups tailored to stage of change to quit smoking, daily contacts, weekly live counseling sessions, and for those ready to quit, six cognitive behavioral therapy counseling sessions. Some TSP groups were assigned randomly to receive a monetary incentive for engagement. Control provided referral to the National Cancer Institute Smokefree.gov website. MEASUREMENTS: PRIMARY OUTCOME: Biochemically verified 7-day abstinence over 12 months. SECONDARY OUTCOMES: Post-treatment (3-month) abstinence; reported abstinence, quit attempt, reduction in smoking, readiness to quit smoking over 12 months. FINDINGS: Verified 7-day abstinence was not significantly different for intervention compared with control over 1 year: month 3 (8.3 versus 3.2%), 6 (6.2 versus 6.0%), and 12 (5.9 versus 10.0%); odds ratio (OR) = 1.07; 95% confidence interval (CI) = 0.23, 4.97; retention = 71%. There was an effect at 3 months (OR = 2.52; CI = 1.56, 4.04; P < 0.0001). There were no 12-month treatment effects for reported abstinence (P = 0.746), reduction in smoking by 50% or more (P = 0.533), likelihood of having made a quit attempt (P = 0.387) or stage of change over time (0.968). Participants in TSP engaged more and rated the intervention more favorably than those in the control condition. CONCLUSIONS: Compared with referral to a smoking cessation website, a novel USA-focused Facebook smoking cessation intervention did not improve abstinence from smoking over 1 year, but increased abstinence at the end of treatment and was engaging to participants. PMID- 29797620 TI - Spontaneous resting-state gamma oscillations are not predictive of autistic traits in the general population. AB - The autism spectrum hypothesis states that not only diagnosed individuals but also individuals from the general population exhibit a certain amount of autistic traits. While this idea is supported by neuroimaging studies, there have been few electrophysiological studies. In particular, there have been no spontaneous resting-state studies yet. In order to examine the autism spectrum hypothesis, the present study tried to predict the level of autistic traits typically developing young adults (n = 93) exhibit from spontaneous resting-state gamma power, a measure that has been linked to social functioning impairments seen in autism. The influence of age and gender was controlled for by employing regression. It was expected that enhanced gamma activity would be predictive of self-reported autistic traits. The model with only age and gender included reached significance, with higher age within this student population being related to more autistic traits. However, no relationship between either low (30 50 Hz) or high (50-70 Hz) gamma power and autistic traits was found. Models with eyes closed low gamma asymmetry and eyes closed high gamma asymmetry included did reach significance, but these findings were not robust, and the gamma asymmetry explained very little additional variance above age and gender. In addition, exploratory correlation analyses showed no relationship between the other power spectra (delta, theta, alpha and beta) on the one hand and autistic traits on the other hand, suggesting that any relationship between spontaneous resting-state brain electrophysiology and autistic traits might not be strong enough to be detected in the general population. PMID- 29797622 TI - Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi-target screening of oral fluid. AB - BACKGROUND AND OBJECTIVES: Numbers of drug-related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved. Opioid maintenance treatment (OMT) is a well-established therapy option among people with opioid dependence. The aim of this study was to assess concomitant substance abuse in opioid-dependent patients under OMT in two centers in Munich, Germany. METHODS: Oral fluid samples of opioid-dependent patients (n = 388) in OMT were randomly collected and analyzed by a multi-drug screening covering a wide range of psychotropic agents with UPLC-MS/MS techniques. RESULTS: Fifty-one percent of the patients had concomitant substance abuse of at least one non-prescribed substance, 32% were positive for substances that were not tested in routine urine diagnostics, especially pregabalin. Fifty-seven percent received take-home opioid medication, and 26% had contact with underage children. Among the take-home subgroup, a concomitant substance abuse of 43.5% was detected. Furthermore 52.5% of the patients with contact to underaged children exhibited concomitant substance abuse. CONCLUSIONS: Concomitant substance abuse is a serious issue among OMT patients. Screening for a broader range of substances than usually analyzed, reveals additional relevant abuse among OMT patients, including pregabalin-an anticonvulsant. SCIENTIFIC SIGNIFICANCE: Our study underscores the importance of monitoring a broad range of substances including others than usually screened in opioid-dependent patients in OMT. (Am J Addict 2018;XX:1-6). PMID- 29797623 TI - Synthesis of gem-Difluorinated Spiro-gamma-lactam Oxindoles by Visible-Light Induced Consecutive Difluoromethylative Dearomatization, Hydroxylation, and Oxidation. AB - Described herein is a protocol for visible-light-induced consecutive synthesis of gem-difluorinated spiro-gamma-lactam oxindoles under mild conditions by means of a process involving sequential radical difluoromethylative dearomatization, hydroxylation, and oxidation. The protocol features high chemo- and regioselectivity, good functional group tolerance, and easy scalability. Several of the functionalized spirooxindole products showed good fungicidal activity, suggesting that they have potential agrochemical applications. PMID- 29797624 TI - Histone lysine methyltransferases BnaSDG8.A and BnaSDG8.C are involved in the floral transition in Brassica napus. AB - Although increasing experimental evidence demonstrates that histone methylations play important roles in Arabidopsis plant growth and development, little information is available regarding Brassica napus. In this study, we characterized two genes encoding homologues of the Arabidopsis histone 3 lysine 36 (H3K36) methyltransferase SDG8, namely, BnaSDG8.A and BnaSDG8.C. Although no duplication of SDG8 homologous genes had been previously reported to occur during the evolution of any sequenced species, a domain-duplication was uncovered in BnaSDG8.C. This duplication led to the identification of a previously unknown NNH domain in the SDG8 homologues, providing a useful reference for future studies and revealing the finer mechanism of SDG8 function. One NNH domain is present in BnaSDG8.A, while two adjacent NNH domains are present in BnaSDG8.C. Reverse transcriptase-quantitative polymerase chain reaction analysis revealed similar patterns but with varied levels of expression of BnaSDG8.A/C in different plant organs/tissues. To directly investigate their function, BnaSDG8.A/C cDNA was ectopically expressed to complement the Arabidopsis mutant. We observed that the expression of either BnaSDG8.A or BnaSDG8.C could rescue the Arabidopsis sdg8 mutant to the wild-type phenotype. Using RNAi and CRISPR/Cas9-mediated gene editing, we obtained BnaSDG8.A/C knockdown and knockout mutants with the early flowering phenotype as compared with the control. Further analysis of two types of the mutants revealed that BnaSDG8.A/C are required for H3K36 m2/3 deposition and prevent the floral transition of B. napus by directly enhancing the H3K36 m2/3 levels at the BnaFLC chromatin loci. This observation on the floral transition by epigenetic modification in B. napus provides useful information for breeding early-flowering varieties. PMID- 29797625 TI - "Abnormal" Addition of NHC to a Conjugate Acid of CAAC: Formation of N-Alkyl Substituted CAAC. AB - The addition reactions of N-heterocyclic carbenes (NHCs) are mostly known to occur through the carbenic centre (C2), which leads to a "normal" adduct. Herein, we report the "abnormal" addition of NHCDip 1 (1,3-(2,6-iPr2 C6 H3 )-imidazole-2 ylidene) to a conjugate acid of cyclic (alkyl)(amino)carbene 2 (CAACiPr =1-iPr 3,3,5,5-Me4 -pyrrolinium triflate). Mechanistic study revealed that this reaction proceeded through the in situ formation of 1,3-(2,6-iPr2 C6 H3 )-imidazolium cation 4 and N-iPr-substituted CAAC 5 followed by the oxidative addition of compound 5 across the C4-H bond (alias backbone C-H) of compound 4. The in situ formation of compound 5 was also proven by the oxidative addition of it to the N H group of iPrNH2 . DFT calculations also supported the mechanistic findings. A different methodology for the in situ generation of compound 5 by using TMPLi is also described. PMID- 29797626 TI - Embryonal Tumor with Multilayered Rosettes, C19MC-Altered: Clinical, Pathological, and Neuroimaging Findings. AB - BACKGROUND AND PURPOSE: Embryonal tumor with multilayered rosettes (ETMR), C19MC altered, is a recently described, rare central nervous system tumor. To our knowledge, the imaging findings of this tumor have not been systematically evaluated in the neuroradiology literature. We present here the clinical, radiological, and pathological correlation of a case series of this very rare tumor, including the full range of anatomic compartment presentations (supratentorial, infratentorial, and spinal). METHODS: We retrospectively analyzed 7 (4M, 3F) pathologically-proven cases of ETMR referred to our institution between 2007 and 2017. We demonstrate the imaging characteristics of this tumor on CT and MRI with advanced imaging. RESULTS: All of the patients are children (ages 1-12). On MR imaging of ETMR, contrast enhancement is often heterogeneous and minimal if any, and there is no significant surrounding T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity to suggest edema. The lesions were often expansile with no evidence of infiltration of the fiber tracks that were displaced by the tumor mass. Diffusion-weighted imaging often demonstrated restricted diffusion within ETMRs. On magnetic resonance spectroscopy (MRS), the choline/creatine (Cho/Cr) ratio is increased, with low N acetylaspartate (NAA) or NAA/Cho ratio, typical of high-grade tumors. CONCLUSION: We demonstrate the conventional and advanced imaging characteristics of ETMR, including MRS and diffusion tensor imaging, which, to our knowledge, have not been systematically evaluated in the radiology literature. The knowledge gained may potentially impact patient management, especially in inoperable cases and in locations where it is risky to perform a biopsy. PMID- 29797627 TI - Iodonium Salts as Benzyne Precursors. AB - Reactions involving benzyne and aryne intermediates have found widespread application in organic synthesis. Various benzyne precursors and benzyne generating procedures are known. Recently, methods of benzyne generation from diaryliodonium salts and related hypervalent iodine compounds have received considerable attention. These methods are characterized by mild reaction conditions and applicability in a broad range of chemical transformations. The present minireview is focused on the preparation and reactivity of hypervalent iodine based benzyne precursors. Furthermore, recent developments in their synthetic application are discussed. PMID- 29797628 TI - Fishing for G-Quadruplexes in Solution with a Perylene Diimide Derivative Labeled with Biotins. AB - A new fluorescent, non-cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G-quadruplexes with scarce or no affinity towards single- or double-stranded DNA. These features have made it possible to design a simple, effective, safe, cheap, and selective method for fishing G-quadruplex structures in solution by use of PDI2B and streptavidin coated magnetic beads. The new cyclic method reported leads to the recovery of more than 80 % of G-quadruplex structures from solution, even in the presence of an excess of single-stranded or duplex DNA as competitors. Moreover, PDI2B is a G4 ligand that can display higher thermal stabilization and greater affinity for 2- over 3-tetrad quadruplexes, which constitutes a novel type of behavior. PMID- 29797629 TI - Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain. AB - BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS. PMID- 29797630 TI - Histopathological analysis of aggressive renal cell carcinoma harboring a unique germline mutation in fumarate hydratase. AB - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterized by cutaneous and uterine leiomyomatosis with RCC. This disorder is caused by a germline mutation in the fumarate hydratase (FH) gene, which encodes an important enzyme of the tricarboxylic acid (TCA) cycle. This mutation distinguishes HLRCC from sporadic RCCs. Herein, we investigated a case of HLRCC in a 32-year-old man who underwent nephrectomy for treatment of a solid cystic tumor in the left kidney. Histopathology demonstrated a variegated architecture of papillary, tubulocystic and cribriform patterns composed of high grade tumor cells with enlarged nuclei and eosinophilic nucleoli. Immunostaining and western blotting revealed no FH expression in the tumor. Genomic DNA sequencing identified a heterozygous mutation involving deletion of the 3' end of exon 2 and intron 2 of the FH gene (c.251_267+7delTGACAGAACGCATGCCAGTAAGTG), and RT-PCR confirmed exon 2 skipping in FH mRNA. The somatic FH gene status of the tumor showed only the mutated allele, indicating loss of heterozygosity as the "second hit" of tumor suppressor gene inactivation. These data support that an FH mutation involving the splice site causes exon skipping, changing the conformation of the protein and accelerating carcinogenic cascades under impaired FH functioning in the TCA cycle. PMID- 29797631 TI - The complex terrain of peer support in mental health: What does it all mean? PMID- 29797632 TI - Risk factors associated with Clostridium difficile infection in kidney transplant recipients. AB - BACKGROUND: Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. METHODS: This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (+/-60 days). RESULTS: The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR = 1.25, 95% CI = 1.00-1.56, P = .048) and antibiotic exposure for urinary tract infections (UTI) (AOR = 4.17, 95% CI = 1.12 15.54, P = .034). Proton pump inhibitor use was not associated with CDI (OR = 0.81, 95% CI = 0.29-2.29, P = .691). CONCLUSION: Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population. PMID- 29797633 TI - Annual stroke incidence in Nigerian children with sickle cell disease and elevated TCD velocities treated with hydroxyurea. AB - BACKGROUND: Elevated transcranial Doppler (TCD) velocities accurately predict stroke risk in children with sickle cell disease (SCD). Chronic blood transfusion, the gold standard for primary stroke prevention, is faced with numerous challenges in Africa. Hydroxyurea (HU) has been shown to reduce elevated TCD velocities in children with SCD. AIM: To determine the effectiveness of HU in reducing the risk of primary stroke in a cohort of Nigerian children with SCD and elevated velocities treated with HU. METHODS: Children with SCD and TCD velocities >=170 cm/sec treated with HU were prospectively followed with 3 monthly TCD and neurological evaluations for >=12 months to determine the incidence of primary stroke. RESULTS: One hundred and four children, 53 males, and 51 females were enrolled into the study. Their ages ranged from 2 to 16 years with a mean of 6 years. At first TCD examination, velocities ranged from 173 to 260 cm/sec with conditional and abnormal risk velocities in 60 (57.7%) and 44 (42.3%) children, respectively. Follow up ranged from 1 to 8 years with a mean of 3.6 years. Mean TCD velocities showed a significant decline from 198.2 (standard deviation [SD] = 15.6) cm/sec to 169.3 (SD = 21.4) cm/sec (P < 0.001). One stroke event occurred in the cohort, giving a stroke incidence of 0.27/100 person years. CONCLUSION: HU significantly reduces TCD velocities in Nigerian children with SCD and elevated TCD velocities, with a corresponding reduction in the incidence of primary stroke. HU may represent a potential alternative for primary stroke prevention in low and middle income countries where the burden of SCD resides. PMID- 29797634 TI - Clinical significance of MYCN amplification in patients with high-risk neuroblastoma. AB - BACKGROUND: This study investigated the clinical significance of MYCN amplification within high-risk neuroblastoma (NB). METHODS: Medical records of 135 patients who were diagnosed with high-risk NB from 2004 to 2016 were reviewed. RESULTS: Fifty-one (38%) patients had MYCN amplified tumors, and the remaining 84 (62%) had nonamplified tumors. MYCN amplification was associated with abdominal primary site, less differentiated pathology, higher levels of lactate dehydrogenase and neuron-specific enolase (NSE), lower vanillylmandelic acid level, and larger primary tumor volume at diagnosis. MYCN amplification was associated with a better early response (faster reduction of primary tumor volume and NSE level). The proportion of patients in complete response or very good partial response after induction treatment was relatively higher in MYCN amplified tumors than in nonamplified tumors; however, all progressions during induction treatment occurred only in MYCN amplified tumors (P = 0.007). The time to progression was shorter (median 1.5 years vs. 1.9 years, P = 0.037) and survival after relapse/progression was worse in MYCN amplified tumors (3 year overall survival: 7.7 +/- 7.4% vs. 20.5 +/- 8.8%, P = 0.046). There was no difference in event-free survival and overall survival between MYCN amplified and nonamplified tumors. CONCLUSION: MYCN amplification was associated with more aggressive features at diagnosis and a better early response, but a higher progression rate during induction treatment and lower chance of survival after relapse/progression. There was no difference in survival rates according to MYCN amplification in patients with high-risk NB. PMID- 29797635 TI - Cisplatin-induced nephrotoxicity in patients with advanced neuroblastoma. PMID- 29797636 TI - MnI /AgI Relay Catalysis: Traceless Diazo-Assisted C(sp2 )-H/C(sp3 )-H Coupling to beta-(Hetero)Aryl/Alkenyl Ketones. AB - An unprecedented MnI /AgI -relay-catalyzed C(sp2 )-H/C(sp3 )-H coupling of (vinyl)arenes with alpha-diazoketones is reported, wherein the diazo group was exploited as a traceless auxiliary for control of regioselectivity. Challenging beta-(hetero)aryl/alkenyl ketones were obtained through this operationally simple approach. The cascade process merges denitrogenation, carbene rearrangement, C-H activation, and hydroarylation/hydroalkenylation. The robustness of this method was demonstrated at preparative scale and applied to late-stage diversification of natural products. PMID- 29797637 TI - Mandibular growth in survivors of pediatric parotid gland carcinoma treated with interstitial brachytherapy. AB - BACKGROUND: The aim of the study was to present long-term results of mandibular growth in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. PROCEDURE: Twenty-five survivors of pediatric parotid gland carcinoma treated with iodine-125 seed interstitial brachytherapy were included for quantitative analysis, including three dimensional (3D) cephalometry and measurement of mandibular volume. RESULTS: 3D cephalometry showed that the median fore-and-aft increments of the lengths of the condyle, the ramus, and the body of the mandible were 1.23, 0.19, and 1.66 mm for the affected side, respectively, and were 1.37, 1.95, and 3.42 mm for the unaffected side, respectively. The difference in increments of the ramus was statistically significant between the affected side and the unaffected side (P = 0.003; P < 0.05). Moreover, mandibular volume measurements showed that the median fore-and-aft increments of the volumes of the condyle, the ramus, and the body of the mandible were 290.62, 220.14, and 1706.40 mm3 for the affected side, respectively, and were 269.15, 370.40, and 1469.86 mm3 for the unaffected side, respectively. The difference in increments was statistically significant between the affected side and the unaffected side for the ramus (P = 0.005; P < 0.05) and the body (P = 0.043; P < .05). CONCLUSION: Mandibular growth was affected by interstitial brachytherapy, especially for the ramus, in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. Nevertheless, the impact was mild in these survivors. PMID- 29797638 TI - Nurses' confidence in providing and managing care for older persons with depressive symptoms or depression in long-term care facilities: A national survey. AB - The prevalence of depressive symptoms among older residents in long-term care facilities (LTCFs) is high. Nurses are the main healthcare providers in LTCFs and also the persons responsible for detecting changes in residents' mental function and providing subsequent care. Therefore, it is necessary to understand nurses' knowledge, attitudes, and confidence regarding care for older residents with depressive symptoms or depression. This study aimed to understand nurses' level of knowledge of late-life depression, attitudes towards depression, and confidence levels in caring for older adults with depressive symptoms or depression in LTCFs. A cross-sectional descriptive and correlational research design was used. A nationwide self-report survey was conducted in 2016. Ultimately, 556 valid questionnaires were returned. The study found that LTCF nurses' knowledge about late-life depression was poor, and they also lacked confidence in managing and caring for older persons with depressive symptoms or depression, but nurses' attitudes towards depression were neutral or slightly positive. Moreover, nurses who had greater confidence in providing care for older persons with depression were those with more positive attitudes towards depression, a greater interest level in taking care of older adults with depression, less late-life depression knowledge, longer nursing experience in LTCFs, and a greater interest level in late-life depression issues, and who had read late-life depression pamphlets or taken courses or classes in late-life depression. The findings suggest an urgent need to develop strategies to improve nurses' late-life depression knowledge and increase their confidence in providing care to older residents with depressive symptoms or depression. PMID- 29797639 TI - Psychosocial determinants of physical activity and dietary behaviors in adolescents and young adults with cancer and survivors. AB - BACKGROUND: Survivors of childhood cancer are at increased risk of lifestyle influenced health issues. We sought to understand the association between stages of change (SOC) and psychosocial variables related to modifiable health behaviors: physical activity (PA), dietary fat intake, and intake of fruits and vegetables among adolescents and young adults at different phases of cancer therapy. METHODS: We conducted an exploratory cross-sectional survey of adolescents and young adults currently being treated for cancer or who are survivors of childhood cancer. We evaluated SOC and several psychosocial variables using the previously validated Patient-Centered Assessment and Counseling for Exercise (PACE+): Physical Activity and Diet Surveys for Adolescents tool. Current dietary behaviors were evaluated with 24 hr diet recall. RESULTS: One hundred and eighteen patients participated in the survey. SOC did not vary by phase of treatment. Ethnicity and body mass index were strongly associated with SOC for PA, but not for dietary behaviors. There was a significant association between SOC and self-efficacy, knowledge of strategies, and family or friend support for PA, dietary fat, and fruits and vegetables. Higher self-efficacy and family support were significant variables impacting SOC and participants' reported intake of fruits and vegetables servings. CONCLUSION: We demonstrate that SOC for the investigated behaviors did not change based on phase of treatment, supporting the initiation of lifestyle interventions early on in treatment. We identify several psychosocial variables that may act as important targets for future lifestyle interventions aimed to improve dietary and exercise behaviors in adolescents and young adults with cancer and survivors. PMID- 29797640 TI - DIVERGT screening procedure predicts general cognitive functioning in adult long term survivors of pediatric acute lymphoblastic leukemia: A PETALE study. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Because of major improvements in treatment protocols, the survival rate now exceeds 80%. However, ALL treatments can cause long-term neurocognitive sequelae, which negatively impact academic achievement and quality of life. Therefore, cognitive sequelae need to be carefully evaluated. The DIVERGT is a battery of tests proposed as a screening tool, sensitive to executive function impairments in children and adolescent cancer survivors. Our study aimed at verifying the predictive value of the DIVERGT on general cognitive functioning in adult long-term survivors of ALL. METHODS: ALL survivors completed the DIVERGT 13.4 years, on average, after remission (N = 247). In addition, 49 of these survivors (equally selected amongst those with low, average, and high DIVERGT scores) as well as 29 controls completed a more comprehensive neuropsychological evaluation within a 3-year period from DIVERGT administration. Multivariate regression analysis was used to assess the predictive value of the DIVERGT on general intelligence, mathematics, verbal memory, and working memory. As a follow up analysis, three performance groups were created based on the DIVERGT results. Multivariate analysis of variance (MANOVA) assessed neuropsychological differences between groups. RESULTS: The DIVERGT accurately predicted General Ability Index (GAI) (P < 0.0001), mathematics (P < 0.0001) and verbal memory (P = 0.045). Moreover, the low-performance group consistently had poorer performance than the high-performance and control groups on the neuropsychological tests. CONCLUSION: The DIVERGT is a useful, time-effective screening battery for broader neurocognitive impairments identification in long-term adult ALL survivors. It could be implemented as routine examination in cancer follow-up clinics. PMID- 29797641 TI - Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma. AB - BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy. PMID- 29797642 TI - Therapeutic optimism and attitudes among medical and surgical nurses towards attempted suicide. AB - Identification of the attitudes to consumers admitted to hospital following a suicide attempt and the therapeutic optimism of nurses caring for this cohort is vital to ascertain the level of nursing care provided. A convenience sample of 72 Registered and enrolled nurses from a large metropolitan health service in South Eastern Melbourne, Australia, completed a demographic questionnaire, the Elsom Therapeutic Optimism Scale (ETOS), and the Attitudes to Attempted Suicide Questionnaire (ATAS-Q). Data were analysed using SPSS (version 25). Whilst the ETOS & ATAS-Q correlate positively, themes of shame, blame, misunderstandings, and myths about suicide influence nurses' perspectives when providing suicide attempt aftercare. This may potentially lead to care that is tokenistic and task focused. To develop their professional skill set when providing suicide attempt aftercare, nurses need both formal and informal education and opportunities to reflect on their practice. PMID- 29797643 TI - Hidden care: Revelations of a case-note audit of physical health care in a community mental health service. AB - People with severe mental illness (SMI) are widely reported to be at an increased risk of morbidity and premature death due to physical health conditions. Mental health nurses are ideally placed to address physical and mental health comorbidity as part of their day-to-day practice. This study involved an audit of hardcopy and electronic clinical case-notes of a random sample of 100 people with SMI case managed by community mental health service in metropolitan South Australia, to determine how well physical health conditions and risk factors, screening, and follow-up are recorded within their service records. Every contact between 1 July 2015 and 30 June 2016 was read. One-way ANOVA, Scheffe's test, and Fisher's exact test determined any significant associations across audit variables, which included gender, age, income, living arrangement, diagnosis, lifestyle factors, recording of physical health measures, and carer status. A focus on physical health care was evident from everyday case-note records; however, because this information was 'buried' within the plethora of entries and not brought to the fore with other key information about the person's psychiatric needs, it remained difficult to gain a full picture of potential gaps in physical health care for this population. Under-reporting, gaps and inconsistencies in the systematic recording of physical health information for this population are likely to undermine the quality of care they receive from mental health services, the ability of mental health service providers to respond in a timely way to their physical healthcare needs, and their communication with other healthcare providers. PMID- 29797645 TI - Whole-Cell Biotransformation of Benzene to Phenol Catalysed by Intracellular Cytochrome P450BM3 Activated by External Additives. AB - An Escherichia coli whole-cell biocatalyst for the direct hydroxylation of benzene to phenol has been developed. By adding amino acid derivatives as decoy molecules to the culture medium, wild-type cytochrome P450BM3 (P450BM3) expressed in E.coli can be activated and non-native substrates hydroxylated, without supplementing with NADPH. The yield of phenol reached 59 % when N-heptyl-l-prolyl l-phenylalanine (C7-Pro-Phe) was employed as the decoy molecule. It was shown that decoy molecules, especially those lacking fluorination, reached the cytosol of E. coli, thus imparting in vivo catalytic activity for the oxyfunctionalisation of non-native substrates to intracellular P450BM3. PMID- 29797644 TI - Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood. AB - BACKGROUND: Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease-modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children's Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime. PROCEDURES: Initiated in 2014, the SCCRIP study prospectively recruits patients diagnosed with SCD and includes retrospective and longitudinal collection of clinical, neurocognitive, geospatial, psychosocial, and health outcomes data. Biological samples are banked for future genomics and proteomics studies. The organizational structure of SCCRIP is based upon organ/system-specific working groups and is opened to the research community for partnerships. RESULTS: As of August 2017, 1,044 (92.3% of eligible) patients with SCD have enrolled in the study (860 children and 184 adults), with 11,915 person-years of observation. Population demographics included mean age at last visit of 11.3 years (range 0.7-30.1), 49.8% females, 57.7% treated with hydroxyurea, 8.5% treated with monthly transfusions, and 62.9% hemoglobin (Hb) SS or HbSB0 -thalassemia, 25.7% HbSC, 8.4% HbsB+ -Thalassemia, 1.7% HbS/HPFH, and 1.2% other. CONCLUSIONS: The SCCRIP cohort will provide a rich resource for the conduct of high impact multidisciplinary research in SCD. PMID- 29797646 TI - The burden of sinus disease in cystic fibrosis lung transplant recipients. AB - INTRODUCTION: Sinus disease (SD) in cystic fibrosis (CF) is a known risk factor for disease progression, the upper airways (UAW) being a site of primary colonization with Pseudomonas aeruginosa. UAW may function as reservoir for graft colonization after lung transplantation (LuTx), increasing risk of rejection. Aims of this study were to assess the burden of sinus disease in CF LuTx recipients, considering patient-reported symptoms, endoscopically documented signs and microbiological isolates, comparing colonization between upper and lower airways. METHODS: A prospective, observational study was performed on consecutive CF LuTx recipients, recording history, symptoms, and management of SD. Nasal lavage (NL) was evaluated for UAW colonization, with nasal inspection during bronchoscopy and bronchoalveolar lavage (BAL) used to assess lower airways if clinically indicated. RESULTS: Hundred and fifty-four patients were included. Symptoms of SD were reported in 96 (62%) individuals; 87 (56%) had prior sinus surgery. Only 8 (13%) of 60 individuals undergoing bronchoscopy presented completely normal findings of the nasal cavity. Thirty-six (60%) patients presented the same isolates on both NL and BAL. Polyps and mucosal alterations were significantly less frequently seen endoscopically in patients with normal flora in NL microbiology (respectively, 26% vs 70%, P = .003, and 35% vs 68%, P = .013). CONCLUSIONS: Symptoms of SD affected more than 60% of CF LuTx recipients. Nasal endoscopic inspection identified alterations in 55%. The majority of patients presented the same isolates both on NL and BAL performed on the same visit. These results strongly support a role of paranasal sinuses as "reservoir" for descending re-colonization of the lung graft. PMID- 29797647 TI - Comments on new classification, treatment algorithm and prognosis-estimating systems for sigmoid volvulus and ileosigmoid knotting: necessity and utility. PMID- 29797648 TI - Catalytic Asymmetric Diels-Alder Reaction/[3,3] Sigmatropic Rearrangement Cascade of 1-Thiocyanatobutadienes. AB - A highly efficient asymmetric Diels-Alder/[3,3] sigmatropic rearrangement reaction of methyleneindolinones with 1-thiocyanatobutadienes has been realized by using a chiral N,N'-dioxide/nickel(II) complex as the catalyst. A range of cyclohexenyl isothiocyanates were synthesized in high yields with excellent diastereo- and enantioselectivities. Based on mechanistic studies, a catalytic cycle with possible transition-state models were proposed to explain the process. PMID- 29797649 TI - Metal- and Reagent-Free Dehydrogenative Formal Benzyl-Aryl Cross-Coupling by Anodic Activation in 1,1,1,3,3,3-Hexafluoropropan-2-ol. AB - A selective dehydrogenative electrochemical functionalization of benzylic positions that employs 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) has been developed. The electrogenerated products are versatile intermediates for subsequent functionalizations as they act as masked benzylic cations that can be easily activated. Herein, we report a sustainable, scalable, and reagent- and metal-free dehydrogenative formal benzyl-aryl cross-coupling. Liberation of the benzylic cation was accomplished through the use of acid. Valuable diarylmethanes are accessible in the presence of aromatic nucleophiles. The direct application of electricity enables a safe and environmentally benign chemical transformation as oxidizers are replaced by electrons. A broad variety of different substrates and nucleophiles can be employed. PMID- 29797650 TI - Poikiloderma with neutropenia in a Tunisian patient with a novel C16orf57 gene mutation. AB - Poikiloderma with neutropenia (PN) is a genodermatosis characterized by poikiloderma, permanent neutropenia, recurrent infections, nail abnormalities, and palmoplantar hyperkeratosis. We report the case of a Tunisian patient with PN. Skin lesions started from the face and spread to the extremities and trunk. Neutropenia was initially periodic and concomitant with infections periods. DNA analysis identified a novel homozygous deletion of a 1-bp (c.161delC, p.P54RfsX60) in the C16orf57gene, presumed to be causative. This report presents the variability of the clinical manifestations and evolution of PN and emphasizes the importance of studying other patients with PN to better delineate mutations profile among populations. PMID- 29797651 TI - Sudden spinal hemorrhage in a pediatric case with total body irradiation-induced cavernous hemangioma. AB - Compared to cerebral radiation-induced cavernous hemangiomas (RICHs), little is known about intraspinal RICHs. A 13-year-old male suddenly developed symptomatic spinal hemorrhage eight years after hematopoietic stem cell transplantation using a total body irradiation (TBI) based myeloablative regimen. A solitary small hemangioma was detected on follow-up T2 star weighted magnetic resonance imaging of the spine. His neurological symptoms gradually improved with supportive treatment and rehabilitation, although he experienced rebleeding 2 years later. Intraspinal RICH is very rare but should be recognized as a possible late adverse effect in pediatric patients who received TBI. PMID- 29797652 TI - Burnout in pediatric hematology/oncology-time to address the elephant by name. AB - The last decade has brought increasing recognition that the wellness of health care providers has an impact on the quality of care, patient satisfaction, and health care economics. This review will describe models of burnout, discuss the impact of burnout on medicine with a focus on pediatric hematologists/oncologists, and present interventions that may help ameliorate physician burnout. PMID- 29797653 TI - Late mortality and morbidity among long-term leukemia survivors with Down syndrome: A nationwide population-based cohort study. AB - BACKGROUND: Late health consequences of treatment for childhood leukemia are well documented. Although individuals with Down syndrome (DS) have a substantially increased risk of leukemia, information on late effects in this group is almost nonexistent. The aim of this study was to evaluate the mortality and morbidity among 5-year leukemia survivors with DS. PROCEDURE: We compared 5-year leukemia survivors with leukemia-free individuals with DS. All individuals born with DS in Denmark between 1960 and 2007 and in Sweden between 1973 and 2009 were included. Long-term morbidity was estimated by comparing hospitalization rates between survivors and leukemia-free individuals. RESULTS: In total, we found 6,705 individuals with DS, 84 of whom were 5-year survivors of leukemia. Survivors had a higher risk of death (hazard ratio [HR] 5.9; 95% confidence interval [CI]: 2.7 13) compared with leukemia-free individuals. All deaths (n = 7) among 5-year leukemia survivors were due to relapse. Survivors had a higher hospitalization rate (HR 4.4; 95% CI: 3.1-6.2). However, most of these hospitalizations were due to relapse. Censoring individuals who either had a relapse or were being treated for a relapse more than 5 years from the initial diagnosis (n = 9) attenuated the association (HR 1.4; 95% CI: 1.0-2.1). CONCLUSION: In this study, we found that relapse was the main reason for death and hospitalization among leukemia survivors with DS, and not late effects. These results are reassuring for individuals treated for DS associated with leukemia and their parents. PMID- 29797654 TI - Transplantation of pediatric renal allografts from donors less than 10 kg. AB - Few transplant programs use kidneys from donors with body weight (BW) < 10 kg. We hypothesized that pediatric en bloc transplants from donors with BW < 10 kg would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N = 28). Data were stratified by smaller (donor BW < 10 kg; n = 11) or larger donors (BW > 10 kg; n = 17). Renal volume was assessed during follow-up with ultrasound. Demographic characteristics were similar between the 2 groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 months (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1 day posttransplant, mean total renal volume in the smaller donors was 28 +/- 9 mm3 vs 45 +/- 12 mm3 (P < .01). By 3 weeks, it was 53 +/- 19 mm3 (smaller donors) versus 73 +/- 19 mm3 (larger donors) (P = NS). Complication rates were similar between both groups with 1 case of venous thrombosis in the smaller group. With experience, outcomes are equivalent to those from larger pediatric donors. PMID- 29797655 TI - Hepatitis C genotype change after transplantation utilizing hepatitis C positive donor organs. AB - A shortage in organs for transplantation has led to the increased use of hepatitis C (HCV) infected donor organs for solid organ transplant recipients infected with HCV. However, the donor HCV genotype is not routinely checked or known prior to transplant. Here, we report 4 cases of genotype conversion after transplantation in patients receiving HCV infected donor organs. This change in genotype may potentially impact HCV progression as well as treatment choice for these patients. PMID- 29797656 TI - The price of protection: a defensive endosymbiont impairs nymph growth in the bird cherry-oat aphid, Rhopalosiphum padi. AB - Bacterial endosymbionts have enabled aphids to adapt to a range of stressors, but their effects in many aphid species remain to be established. The bird cherry-oat aphid, Rhopalosiphum padi (Linnaeus), is an important pest of cereals worldwide and has been reported to form symbiotic associations with Serratia symbiotica and Sitobion miscanthi L-type symbiont endobacteria, although the resulting aphid phenotype has not been described. This study presents the first report of R. padi infection with the facultative bacterial endosymbiont Hamiltonella defensa. Individuals of R. padi were sampled from populations in Eastern Scotland, UK, and shown to represent seven R. padi genotypes based on the size of polymorphic microsatellite markers; two of these genotypes harbored H. defensa. In parasitism assays, survival of H. defensa-infected nymphs following attack by the parasitoid wasp Aphidius colemani (Viereck) was 5 fold higher than for uninfected nymphs. Aphid genotype was a major determinant of aphid performance on two Hordeum species, a modern cultivar of barley H. vulgare and a wild relative H. spontaneum, although aphids infected with H. defensa showed 16% lower nymph mass gain on the partially resistant wild relative compared with uninfected individuals. These findings suggest that deploying resistance traits in barley will favor the fittest R. padi genotypes, but symbiont-infected individuals will be favored when parasitoids are abundant, although these aphids will not achieve optimal performance on a poor quality host plant. PMID- 29797657 TI - Chronic median nerve modulation reduces ventricular arrhythmia and improves ventricular function in a postmyocardial infarction rabbit model. AB - AIM: Median nerve stimulation (MNS) is a novel neuromodulation approach for treatment of ventricular arrhythmia, but little is known about its chronic effects. The aim of this study was to investigate the effects of chronic MNS on ventricular arrhythmia and ventricular dysfunction postmyocardial infarction (MI). METHOD: Two weeks after MI, 12 rabbits were randomly divided into control and MNS groups, and chronic MNS was performed in MNS group for 2 weeks. Ventricular function and arrhythmias; sympathetic innervation and activity; and interleukin-1 beta (IL-1 beta) and norepinephrine (NE) levels were analyzed. RESULTS: Both the total number of premature ventricular complex and episodes of ventricular tachycardia were lower in MNS group than in control group (20 560 +/- 10 314 beats vs 70 079 +/- 37 184 beats, P = .021, and 115 +/- 63 episodes vs 307 +/- 164 episodes, P = .034, respectively). Compared with control group, MNS decreased the cardiac sympathetic nerve density and level of circulating NE in MNS group (1798.42 +/- 644.07 MUm2 /mm2 vs 1003.79 +/- 453.00 MUm2 /mm2, P = .041, and 20.86 +/- 4.54 pg/mL vs 11.07 +/- 1.43 pg/mL, P = .002, respectively). MNS also improved the left ventricular ejection fraction (59.07 +/- 1.91% vs 49.77 +/- 3.47%, P = .003) and inhibited the level of IL-1 beta in serum (69.19 +/- 4.71 pg/mL vs 85.93 +/- 12.80 pg/mL, P = .013). CONCLUSION: Chronic MNS appears to protect against ventricular arrhythmia and improves ventricular function post-MI, which may be mediated by suppressing cardiac sympathetic activity and anti-inflammatory effects. PMID- 29797658 TI - Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges. AB - Sickle cell disease (SCD) presents challenges to hematopoietic stem cell transplantation (HSCT), including donor availability and morbidity with age/disease severity. However, severe SCD causes irreversible organ damage that HSCT can mitigate. This benefit must be balanced against preparative regimen toxicity, graft-versus-host disease, and mortality risk. We review efforts to balance HSCT complications with the promise of cure, and knowledge gaps that warrant further investigation. We highlight the burden of SCD, HSCT risks and benefits, and SCD families' approach to this balance. We emphasize the necessity for information exchange to ensure a joint decision-making process between providers and patients. PMID- 29797659 TI - Myeloid lineage switch following chimeric antigen receptor T-cell therapy in a patient with TCF3-ZNF384 fusion-positive B-lymphoblastic leukemia. AB - A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant. A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed phenotype acute leukemias. Lineage switch following CAR-T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion. PMID- 29797661 TI - PdII -Catalyzed Cascade Synthesis of Chromane Derivatives Initiated by cis Chloropalladation or trans-Acetoxypalladation. AB - A highly regio- and stereoselective PdII -catalyzed cascade synthesis of biologically relevant chromane derivatives from easily available enynes was developed under operationally simple conditions. The cascade reaction consists of nucleopalladation of alkynes, insertion of the alkene and protonation. When CuCl2 was employed as nucleophile, a cis-chloropalladation initiates the cascade. Whereas in the case of AcOH, a trans-acetoxypalladation takes place. PMID- 29797660 TI - Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus. AB - Atherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and development of this disease. The regulation and stabilization of these cells are a key therapeutic strategy for DM-associated atherosclerosis. An increasing number of evidences implicate that various types of noncoding RNAs (ncRNAs) play a vital role in many cellular responses as well as in physiological and pathological processes of atherosclerosis and DM that drive atherogenic/antiatherogenic processes in those cells. Encouragingly, many ncRNAs have already been tested in animal experiments or clinical trials showing good performance. In this review, we summarize recent progresses in research on functional regulatory role of ncRNAs in atherosclerosis with DM. More importantly, we illustrate new thoughts and findings relevant to ncRNAs as potential therapeutic targets or biomarkers for atherosclerosis with DM. PMID- 29797663 TI - Interlaboratory method validation of icIEF methodology for analysis of monoclonal antibodies. AB - CE is central to the analysis, process development and approval of therapeutic monoclonal antibodies (mAbs). Recently, imaged capillary isoelectric focusing (icIEF) has emerged as a powerful technique for quantitative protein charge heterogeneity monitoring and characterization, particularly for mAbs. However, icIEF has yet to be validated for therapeutically relevant mAbs adhering to the ICH guideline (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use). Here, for the first time, icIEF technology was validated by 10 laboratories across 8 independent companies using a therapeutic mAb. The parameters of this method validation strictly follow the guideline of the ICH. This guideline includes specificity, precision, accuracy, linearity, range, LOQ and robustness. These results represent a significant step forward in standardizing the use of icIEF methods for the clinical approval of therapeutic mAbs. PMID- 29797662 TI - Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group. AB - INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS. PMID- 29797664 TI - Association between patient-reported hearing and visual impairments and functional, psychological, and cognitive status among older adults with cancer. AB - BACKGROUND: Hearing and visual impairments are common among community-dwelling older adults, and are associated with psychological, functional, and cognitive deficits. However, to the authors' knowledge, little is known regarding their prevalence among older patients with cancer. METHODS: The current study was a secondary analysis combining 2 prospective cohorts of adults aged >=65 years with solid tumors who were receiving chemotherapy. The authors assessed the association between patient-reported hearing and/or visual impairment (defined as fair/poor grading by self-report) and physical function, instrumental activities of daily living (IADLs), anxiety, depression, and cognition. Descriptive analyses were conducted to summarize patient and treatment characteristics. One-way analysis of variance and chi-square tests were conducted as appropriate to examine differences between patients with and without sensory impairments. Logistic regression was used to analyze associations between sensory impairments and outcomes. RESULTS: Among 750 patients with a median age of 72 years who had solid tumors (29% with breast/gynecological tumors, 28% with lung tumors, and 27% with gastrointestinal tumors), approximately 18% reported hearing impairment alone, 11% reported visual impairment alone, and 7% reported dual sensory impairment. Hearing impairment was associated with IADL dependence (odds ratio [OR], 1.9), depression (OR, 1.6), and anxiety (OR, 1.6). Visual impairment was associated with IADL dependence (OR, 1.9), poor physical function (OR, 1.9), and depression (OR, 2.5). Dual impairment was associated with IADL dependence (OR, 2.8), anxiety (OR, 2.3), depression (OR, 2.5), and cognitive impairment (OR, 3.2). CONCLUSIONS: Sensory impairment is common among older adults with cancer. Patients with sensory impairment are more likely to have functional, psychological, and cognitive deficits. Interventions aimed at improving the vision and hearing of older adults with cancer should be studied. Cancer 2018. (c) 2018 American Cancer Society. PMID- 29797666 TI - Healthcare education research: The case for rethinking hierarchies of evidence. PMID- 29797668 TI - Reply to Gambichler T et al.: Altered epigenetic pathways and cell cycle dysregulation in healthy appearing skin of patients with koebnerized squamous cell carcinomas following skin surgery. PMID- 29797665 TI - Fusion status in patients with lymph node-positive (N1) alveolar rhabdomyosarcoma is a powerful predictor of prognosis: Experience of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). AB - BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) with lymph node involvement (N1 classification) accounts for up to 10% of all cases of RMS. The prognosis is poor, and is comparable to that of distant metastatic disease. In the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS2005 protocol, patients with a histologic diagnosis of aRMS/N1 received intensified chemotherapy with systematic locoregional treatment. METHODS: Patients with aRMS/N1 were enrolled prospectively after primary surgery/biopsy and fusion status was assessed in tumor samples. All patients received 9 cycles of induction chemotherapy and 6 months of maintenance therapy. Local treatment included radiotherapy to the primary site and lymph nodes with or without secondary surgical resection. RESULTS: A total of 103 patients were enrolled. The clinical characteristics of the patients were predominantly unfavorable: 90% had macroscopic residual disease after initial surgery/biopsy, 63% had locally invasive tumors, 77% had a tumor measuring >5 cm, and 81% had disease at unfavorable sites. Fusion genes involving forkhead box protein O1 (FOXO1) were detected in 56 of 84 patients. Events occurred in 52 patients: 43 developed disease recurrence, 7 had disease that was refractory to treatment, and 2 patients developed second neoplasms. On univariate analysis, unfavorable disease site, tumor invasiveness, Intergroup Rhabdomyosarcoma Study group III, and fusion-positive status correlated with worse prognosis. The 5-year event-free survival rate of patients with fusion positive tumors was 43% compared with 74% in patients with fusion-negative tumors (P = .01). On multivariate analysis, fusion positivity and tumor invasiveness proved to be unfavorable prognostic markers. CONCLUSIONS: Fusion status and tumor invasiveness appear to have a strong impact on prognosis in patients with aRMS/N1. Fusion status will be used to stratify these patients in the next EpSSG RMS study, and treatment will be intensified in patients with fusion-positive tumors. Cancer 2018. (c) 2018 American Cancer Society. PMID- 29797667 TI - Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib. AB - BACKGROUND: Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown. METHODS: This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib. RESULTS: One hundred forty-five patients received ibrutinib (80% in a relapsed/refractory setting). A high burden of comorbidities (CIRS score >= 7) was associated with inferior median event-free survival (EFS; 24 vs 37 months; P = .003) and 2-year overall survival (OS; 79% vs 100%; P = .005). In an adjusted Cox model, both EFS and OS worsened with an incremental increase in the CIRS score. Furthermore, comorbidities were associated with an increased risk of ibrutinib dose reduction and therapy discontinuation. CIRS was predictive in both frontline and relapsed CLL, regardless of patient age. CONCLUSIONS: Comorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. (c) 2018 American Cancer Society. PMID- 29797669 TI - Tinea capitis in children: a systematic review of management. AB - BACKGROUND: Tinea capitis is the most common cutaneous fungal infection in children. OBJECTIVES: This review aims to evaluate the differences that exist between medications for the treatment of tinea capitis, to determine whether there are any significant adverse effects associated and to define the usefulness of sample collection methods. METHODS: We conducted a systematic literature search of available papers using the databases PubMed, OVID, Cochrane Libraries and ClinicalTrials.gov. Twenty-one RCTs and 17 CTs were found. RESULTS: Among the different antifungal therapies (oral and combination thereof), continuous itraconazole and terbinafine had the highest mycological cure rates (79% and 81%, respectively), griseofulvin and terbinafine had the highest clinical cure rates (46% and 58%, respectively) and griseofulvin and terbinafine had the highest complete cure rate (72% and 92%, respectively). Griseofulvin more effectively treated Microsporum infections; terbinafine and itraconazole more effectively cured Trichophyton infections. Only 1.0% of children had to discontinue medication based on adverse events. T. tonsurans was the most common organism found in North America, and hairbrush collection method is the most efficient method of sample collection. Additionally, using a hairbrush, toothbrush or cotton swab to identify the infecting organism(s) is the least invasive and most efficient method of tinea capitis sample collection in children. CONCLUSIONS: Current dosing regimens of reported drugs are effective and safe for use in tinea capitis in children. PMID- 29797670 TI - Teledermatology-driven topical therapy of actinic keratosis: a comparative study of clinical effectiveness and compliance. AB - BACKGROUND: Teledermatology (TD) provides efficient care for skin cancer patients. OBJECTIVE: To compare the clinical effectiveness of imiquimod 5% for the treatment of AK with in-person care and through TD. METHODS: Longitudinal prospective controlled study including patients with single AK diagnosed and treated at face-to-face visits (FTF group) or through teledermatology (TD group) with imiquimod 5% cream. The main outcome measures assessed were the complete and global response percentage (CR and GR) under per-protocol (PP) and intention-to treat (ITT) analysis. RESULTS: A total of 157 patients were enrolled (FTF = 75, TD = 82). PP analysis showed CR in 66.7% of FTF patients and 65.6% in TD patients (P > 0.05). The ITT yielded CR in 64.0% and 51.2% in FTF visits and TD, respectively (P = 0.073). The analysis showed an advantage of FTF care against TD in achieving GR (84.0% vs. 70.7%; P = 0.036). Facial location and local adverse reactions were the only explanatory factors of complete response in the ITT approach. Treatment completion was found in 90.7% and 72.0% in the FTF and TD groups, respectively (P = 0.004). CONCLUSIONS: Improvements in patient counselling at the primary care centre are needed before the implementation of TD as a routine methodology for the management of AK. PMID- 29797671 TI - CD7 is expressed on a subset of normal CD34-positive myeloid precursors. AB - OBJECTIVE: To improve monitoring of myeloid neoplasms by flow cytometry-based minimal residual disease (MRD) analysis, we analyzed the significance of leukemia associated immunophenotype (LAIP) markers in 44 patients. METHODS: In a pilot study cohort, peripheral blood or bone marrow samples from 13 patients with myeloid neoplasms and one case of B lymphoblastic leukemia in complete hematologic remission after allogeneic bone marrow or stem cell transplantation were subjected to selection for leukemia-specific phenotypes by fluorescence activated cell sorting using individual marker combinations, followed by PCR based chimerism analysis. RESULTS: The feasibility of this method could be demonstrated, with selection being successful in 12 cases, including two cases where mixed chimerism was found exclusively in sorted cells. Interestingly, four specimens displayed full donor chimerism in cells expressing the presumably aberrant combination CD34+ /CD7+ . Further analyses, including assessment of an independent cohort of 25 patients not affected by neoplastic bone marrow infiltration, revealed that normal myeloid precursors usually include a population coexpressing CD34, CD13, CD33, and CD7. CONCLUSION: We conclude that the combination CD34+ /CD7+ might not be suitable as an LAIP for MRD diagnostics and that a subset of normal myeloid precursors in the bone marrow expresses CD7. PMID- 29797672 TI - Biocatalytic potential of Streptomyces spp. isolates from rhizosphere of plants and mycorrhizosphere of fungi. AB - Biocatalytic potential of Streptomyces strains isolated from the rhizosphere of plants and from mycorrhizosphere of fungi has been investigated. A total of 118 Streptomyces isolates were selected and functionally screened for 10 different biotechnologically important enzymatic activities: hydrolase (cellulase, cutinase, gelatinase, lipase, protease, polyhydroxyalkanoate (PHA) depolymerase), phenol oxidase and peroxidase (laccase, tyrosinase, and lignin peroxidase), and aminotransferase. Out of 118 tested Streptomyces spp., 90% showed at least one enzymatic activity. The most abundant were enzymes involved in the biomass degradation, as the production of cutinase, cellulase, and lignin peroxidase were detected in 31%, 40%, and 48% of the isolates, respectively. The improved specific activities of lipase (isolates BV315 and BV100) and tyrosinase (isolates BV87 and BV88) were shown in comparison with the industrially relevant activities of Pseudomonas strains. Plant rhizosphere soils were more prolific source of Streptomyces strains with biocatalytic potential in comparison with mycorrhizosphere soils. Overall, 284 enzyme activities among 118 Streptomyces isolates have been detected. This is the first comprehensive screening of Streptomyces isolates from rhizosphere and mycorrhizosphere soils for novel biocatalysts, showing that specific environmental habitats, such as rhizosphere soils, are "treasure troves" of Streptomyces with biocatalytic potential. PMID- 29797674 TI - Response: field cancerization and koebnerized skin tumours. PMID- 29797673 TI - Muscle radiodensity and mortality in patients with colorectal cancer. AB - BACKGROUND: Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. METHODS: This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between 2006 and 2011 with AJCC stages I to III CRC. The authors evaluated hazard ratios (HRs) of low SMD for all-cause and CRC-specific mortality, assessed by computed tomography using optimal stratification, compared with patients with normal SMD. They also evaluated the cross-classification of categories of low versus normal SMD and muscle mass (MM) with outcomes. RESULTS: The median follow-up was 6.9 years. Optimal stratification cutpoints for SMD were 32.5 in women and 35.5 in men. In multivariate-adjusted analyses, among patients with CRC, those with low SMD demonstrated higher overall (HR, 1.61; 95% confidence interval [95% CI], 1.36 1.90) and CRC-specific (HR, 1.74; 95% CI, 1.38-2.21) mortality when compared with those with normal SMD levels. Patients with low SMD and low MM (ie, sarcopenia) were found to have the highest overall (HR, 2.02; 95% CI, 1.65-2.47) and CRC specific (HR, 2.54; 95% CI, 1.91-3.37) mortality rates. CONCLUSIONS: In patients with CRC, those with low SMD were found to have elevated risks of disease specific and overall mortality, independent of MM or adiposity. Clinical practice should incorporate body composition measures into the evaluation of the health status of patients with CRC. Cancer 2018;124:3008-15. (c) 2018 American Cancer Society. PMID- 29797675 TI - Spiro-epoxyglycosides as Activity-Based Probes for Glycoside Hydrolase Family 99 Endomannosidase/Endomannanase. AB - N-Glycans direct protein function, stability, folding and targeting, and influence immunogenicity. While most glycosidases that process N-glycans cleave a single sugar residue at a time, enzymes from glycoside hydrolase family 99 are endo-acting enzymes that cleave within complex N-glycans. Eukaryotic Golgi endo 1,2-alpha-mannosidase cleaves glucose-substituted mannose within immature glucosylated high-mannose N-glycans in the secretory pathway. Certain bacteria within the human gut microbiota produce endo-1,2-alpha-mannanase, which cleaves related structures within fungal mannan, as part of nutrient acquisition. An unconventional mechanism of catalysis was proposed for enzymes of this family, hinted at by crystal structures of imino/azasugars complexed within the active site. Based on this mechanism, we developed the synthesis of two glycosides bearing a spiro-epoxide at C-2 as electrophilic trap, to covalently bind a mechanistically important, conserved GH99 catalytic residue. The spiro epoxyglycosides are equipped with a fluorescent tag, and following incubation with recombinant enzyme, allow concentration, time and pH dependent visualization of the bound enzyme using gel electrophoresis. PMID- 29797676 TI - The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis. AB - BACKGROUND: The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated. AIMS, MATERIALS AND METHODS: This post-hoc analysis included data from 273 CMV seropositive kidney transplant recipients randomized to receive anti-thymocyte globulin and everolimus (rAGT/TAC/EVR, n = 81), basiliximab and everolimus (BAS/TAC/EVR, n = 97) or basiliximab and mycophenolate (BAS/TAC/MPS, n = 95). All patients received tacrolimus (TAC) and corticosteroids. Preemptive CMV therapy based on weekly pp65 antigenemia test was used during the first 6 months. Blinded weekly CMV DNAemia was compared among the groups. RESULTS: The proportion of patients with undetectable CMV DNAemia (23.4% vs 56.7% vs 22.1%, P < .001) was higher in the BAS/TAC/EVR. The median number of study visits with positive CMV DNAemia (2.0 vs 0.0 vs 4.6, rATG/EVR vs BAS/MPS, P = .354; BAS/EVR vs BAS/MPS, P < .0001; rATG/EVR vs BAS/EVR, P < .001) were lower in the BAS/TAC/EVR. The proportion of patients with positive CMV DNAemia who were not treat for CMV infection/disease based on pp65 antigenemia was higher in rATG/TAC/EVR group (74.1% vs 36.1% vs 44.2%, P < .001) but mean CMV DNAemia was comparable to BAS/TAC/EVR and lower than BAS/TAC/MPS (8536 +/- 15 899 vs 7975 +/- 17 935 vs 16 965 +/- 37 694 copies/mL, P < .05), respectively. The proportion of patients with CMV DNAemia below 5000 copies/mL was higher in patients receiving EVR (74.1% vs 83.5% vs 50.0%, P = .000), respectively. DISCUSSION AND CONCLUSION: These data suggest that mTOR inhibitors reduce the incidence of CMV infection by limiting CMV viral replication. PMID- 29797678 TI - Immediate histopathologic follow-up of cervista and aptima high-risk HPV assays in women with LSIL cytology. AB - BACKGROUND: Recent guidelines recommended the optional deferral of colposcopy for postmenopausal women with low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) test results and negative human papillomavirus (HPV) testing. The objective of the current study was to assess the histopathologic follow-up of Cervista and Aptima high-risk HPV (hrHPV) testing in patients with LSIL cytology. METHODS: Women with LSIL Pap test results and Cervista or Aptima hrHPV testing results were retrospectively identified from June 2013 through July 2017. Histological follow-up results within 6 months after LSIL Pap tests were analyzed. RESULTS: A total of 1731 and 1906 cases of LSIL Pap tests, respectively, were tested on Cervista and Aptima platforms. Among the 2119 cases with histopathologic follow-up, cervical intraepithelial neoplasia of types 2/3 (CIN2/3) was diagnosed in 184 women (8.9%) and the detection rate was significantly higher in women with positive HPV testing compared with those with a negative result on both assays. Both methods demonstrated comparable performance for detecting CIN2/3 lesions. However, in women aged >=50 years, the specificity for the detection of CIN2/3 lesions by the Aptima assay was statistically significantly higher than that of the Cervista test (48.7% vs 23.1%; P<.01), although there were no significant differences in the sensitivity, positive predictive value, and negative predictive value between these 2 assays in this age group. CONCLUSIONS: The Aptima assay was found to be statistically significantly more specific than the Cervista test for detecting CIN2/3 lesions among women aged >=50 years. These findings not only further support the recommendations by the American Society for Colposcopy and Cervical Pathology that hrHPV triage is an acceptable option for postmenopausal women with LSIL cytology, but also provide additional evidence that HPV RNA testing may be more useful in clinical risk stratification due to its specificity in the postmenopausal population. Cancer Cytopathol 2018. (c) 2018 American Cancer Society. PMID- 29797677 TI - Severe hematuria in a hematopoietic cell transplant recipient caused by Ureaplasma urealyticum not by BK virus or adenovirus infection. AB - A 17-year-old male with acute lymphoblastic leukemia developed severe hematuria and scrotal swelling after haploidentical hematopoietic cell transplantation (HCT). Urine culture was negative. BK virus and adenovirus were negative. However, Ureaplasma urealyticum was detected. He showed dramatic improvement after doxycycline treatment. This is the first report in the literature of hemorrhagic cystitis caused by U. urealyticum in a HCT recipient. In HCT recipients with hemorrhagic cystitis, U. urealyticum should be considered as a potential cause. PMID- 29797679 TI - Parathyroid hormone-related peptide activates and modulates TRPV1 channel in human DRG neurons. AB - Parathyroid hormone-related peptide (PTHrP) is associated with advanced tumor growth and metastasis, especially in breast, prostate and myeloma cancers that metastasize to bones, resulting in debilitating chronic pain conditions. Our recent studies revealed that the receptor for PTHrP, PTH1R, is expressed in mouse DRG sensory neurons, and its activation leads to flow-activation and modulation of TRPV1 channel function, resulting in peripheral heat and mechanical hypersensitivity. In order to verify the translatability of our findings in rodents to humans, we explored whether this signalling axis operates in primary human DRG sensory neurons. Analysis of gene expression data from recently reported RNA deep sequencing experiments performed on mouse and human DRGs reveals that PTH1R is expressed in DRG and tibial nerve. Furthermore, exposure of cultured human DRG neurons to PTHrP leads to slow-sustained activation of TRPV1 and modulation of capsaicin-induced channel activation. Both activation and modulation of TRPV1 by PTHrP were dependent on PKC activity. Our findings suggest that functional PTHrP/PTH1R-TRPV1 signalling exists in human DRG neurons, which could contribute to local nociceptor excitation in the vicinity of metastatic bone tumor microenvironment. PMID- 29797680 TI - Cytopathologic features of SMARCB1 (INI-1)-deficient sinonasal carcinoma. AB - BACKGROUND: SMARCB1 (INI-1)-deficient sinonasal carcinoma (IDSNC) is a newly described, poorly differentiated carcinoma. Herein, the authors describe the cytopathologic features of IDSNC in fine-needle aspiration (FNA) samples. METHODS: The pathology archives of 2 academic institutions were searched for cases of IDSNC with available cytologic materials. All available slides were reviewed and a detailed morphological analysis was performed. RESULTS: Six cases were identified from 6 patients. FNA specimens were obtained from metastatic sites (4 cases), a local disease recurrence (1 case), and a primary lesion extending into the orbit (1 case). The majority of cases had cellular specimens with features of nonkeratinizing squamous cell carcinoma composed of cohesive clusters and sheets of oval to polygonal cells with indistinct cell borders present within a background of necrotic debris. Two cases had single rhabdoid cells with more abundant cytoplasm. The nuclei generally were small and uniform with fine chromatin, small nucleoli, and mild nuclear membrane irregularities; moderate anisonucleosis and multinucleation were noted in one case. Apoptotic bodies were common in 5 of 6 cases, and readily identifiable mitoses in 3 of 6 cases. Immunohistochemistry demonstrated that all cases expressed cytokeratins, 4 of 5 cases expressed p63, and all cases demonstrated loss of INI-1 nuclear expression. All cases were negative for neuroendocrine markers and aberrant p16 staining. CONCLUSIONS: A diagnosis of IDSNC can be suspected on FNA specimens from patients with high-grade sinonasal carcinomas that have either a nonkeratinizing squamous cell carcinoma or rhabdoid morphology. Clinical history and the availability of material for immunohistochemistry are key in confirming the diagnosis. Cancer Cytopathol 2018. (c) 2018 American Cancer Society. PMID- 29797681 TI - Does the urinary tract infection caused by carbapenem-resistant Gram-negative bacilli impact the outcome of kidney transplant recipients? AB - The incidence of urinary tract infection (UTI) after kidney transplantation (KT) caused by multidrug-resistant (MDR) bacteria is growing. The aim of this study was to analyze the impact of UTI caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) in the survival of graft and recipients following KT. This was a retrospective cohort study involving patients who underwent KT between 2013 and 2016. Patients were followed since the day of the KT until loss of graft, death or end of the follow-up period (31th December 2016). The outcomes measured were UTI by MDR following KT and graft and patient survival. Analyses were performed using Cox regression; for the graft and patient survival analysis, we used a propensity score for UTI by CR-GNB to matching a control group. UTI was diagnosed in 178 (23.9%) of 781 patients, who developed 352 UTI episodes. 44.6% of the UTI cases were caused by MDR bacteria. Identified risk factors for UTI by MDR bacteria were DM, urologic disease as the cause of end-stage renal failure, insertion of ureteral stent, carbapenem use, and delayed graft function (DGF). Risk factors for death during the follow-up period were female gender, patients over 60 years old at the time of KT, DM, body mass index over 31.8, UTI caused by CR-GNB. In conclusion, UTIs caused by CR-GNB have great impact on patients' survival after KT. PMID- 29797682 TI - Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS. AB - We report on the quantitative proteomic analysis of single mammalian cells. Fluorescence-activated cell sorting was employed to deposit cells into a newly developed nanodroplet sample processing chip, after which samples were analyzed by ultrasensitive nanoLC-MS. An average of circa 670 protein groups were confidently identified from single HeLa cells, which is a far greater level of proteome coverage for single cells than has been previously reported. We demonstrate that the single-cell proteomics platform can be used to differentiate cell types from enzyme-dissociated human lung primary cells and identify specific protein markers for epithelial and mesenchymal cells. PMID- 29797685 TI - NMR in Biomedicine 30th Anniversary Volume Message from the Editor-in-Chief. PMID- 29797684 TI - Deconstructing the King megafire. AB - Hypotheses that megafires, very large, high-impact fires, are caused by either climate effects such as drought or fuel accumulation due to fire exclusion with accompanying changes to forest structure have long been alleged and guided policy, but their physical basis remains untested. Here, unique airborne observations and microscale simulations using a coupled weather-wildland-fire behavior model allowed a recent megafire, the King Fire, to be deconstructed and the relative impacts of forest structure, fuel load, weather, and drought on fire size, behavior, and duration to be separated. Simulations reproduced observed details including the arrival at an inclined canyon, a 25-km run, and later slower growth and features. Analysis revealed that fire-induced winds that equaled or exceeded ambient winds and fine-scale airflow undetected by surface weather networks were primarily responsible for the fire's rapid growth and size. Sensitivity tests varied fuel moisture and amount across wide ranges and showed that both drought and fuel accumulation effects were secondary, limited to sloped terrain where they compounded each other, and, in this case, unable to significantly impact the final extent. Compared to standard data, fuel models derived solely from remote sensing of vegetation type and forest structure improved simulated fire progression, notably in disturbed areas, and the distribution of burn severity. These results point to self-reinforcing internal dynamics rather than external forces as a means of generating this and possibly other outlier fire events. Hence, extreme fires need not arise from extreme fire environment conditions. Kinematic models used in operations do not capture fire induced winds and dynamic feedbacks so can underestimate megafire events. The outcomes provided a nuanced view of weather, forest structure, fuel accumulation, and drought impacts on landscape-scale fire behavior-roles that can be misconstrued using correlational analyses between area burned and macroscale climate data or other exogenous factors. A practical outcome is that fuel treatments should be focused on sloped terrain, where factors multiply, for highest impact. PMID- 29797683 TI - Breakthrough Candida guilliermondii (Meyerozyma guilliermondii) fungemia after cord blood transplantation for extranodal NK-cell lymphoma with azole prophylaxis. AB - Fluconazole (FLCZ) is an azole antifungal agent and it has shown excellent clinical activities in suppressing fungemia with Candida albicans after hematopoietic stem cell transplantation. Increased administration of prophylactic FLCZ seems to have given rise to the relatively higher incidence of more resistant Candida non-albicans infection. We present a case with a rare breakthrough fungemia with C. guilliermondii after cord blood transplantation for Extranodal NK cell Lymphoma, nasal type (ENKL), during antifungal prophylaxis with FLCZ. High level of caution is needed for the breakthrough, especially after long-term azole administration. PMID- 29797686 TI - Direct quantitation of endogenous steroid sulfates in human urine by liquid chromatography-electrospray tandem mass spectrometry. AB - A method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the direct quantitation of endogenous steroid sulfates has been developed to be able to evaluate these metabolites as biomarkers to detect the misuse of endogenous androgenic anabolic steroids in sports. For sample preparation, a mixed-mode solid-phase extraction was optimized to eliminate the glucuronide fraction in the washing step thus obtaining only the sulfate fraction. Chromatographic separation was optimized to achieve adequate resolution between isomers. The electrospray ionization and the product ion mass spectra of the sulfates were studied in order to obtain the most specific and selective transitions. The method was validated for quantitative purposes for 11 steroid sulfates obtaining satisfactory values for linearity, accuracy, and intra- and inter-day precision (relative standard deviation better than 16.2%). Limits of quantitation ranged between 0.5 and 2 ng/mL. Extraction recoveries for sulfate metabolites were between 90 and 94%. Matrix effect ranged from 90 to 110% showing the absence of significant ion suppression/enhancement. Samples were found to be stable after 2 freeze/thaw cycles. The applicability of the method was checked by the analysis of 75 urine samples from healthy volunteers (54 males, 37 Caucasian and 17 Asian, and 21 Caucasian females) to evaluate the concentration levels of endogenous sulfate metabolites in basal conditions. PMID- 29797687 TI - Monitoring dehydroepiandrosterone (DHEA) in the urine of Thoroughbred geldings for doping control purposes. AB - The use of testosterone and its pro-drugs, such as dehydroepiandrosterone (DHEA), is currently regulated in horseracing by the application of international testosterone thresholds. However, additional steroidomic approaches, such as steroid ratios, to distinguish overall adrenal stimulation from drug administrations and an equine biological passport for longitudinal steroid profiling of individual animals could be advantageous in equine doping testing. Thus, DHEA concentrations and related ratios (testosterone [T] to DHEA and DHEA to epitestosterone [E]) were assessed in the reference population by quantitative analysis of 200 post-race gelding urine samples using liquid chromatography tandem mass spectrometry. DHEA concentrations ranged between 0.9 and 136.6 ng/mL (mean 12.8 ng/mL), T:DHEA ratios between 0.06 and 1.85 (mean 0.43), and DHEA:E ratios between 0.21 and 13.56 (mean 2.20). Based on the reference population statistical upper limits of 5.4 for T:DHEA ratio and 48.1 for DHEA:E ratio are proposed with a risk of 1 in 10 000 for a normal outlier exceeding the value. Analysis of post-administration urine samples collected following administrations of DHEA, Equi-Bolic(r) (a mix of DHEA and pregnenolone) and testosterone propionate to geldings showed that the upper limit for T:DHEA ratio was exceeded following testosterone propionate administration and DHEA:E ratio following DHEA administrations and thus these ratios could be used as additional biomarkers when determining the cause of an atypical testosterone concentration. Additionally, DHEA concentrations and ratios can be used as a starting point to establish reference ranges for an equine biological passport. PMID- 29797688 TI - Tuberculin skin test, Interferon gamma release assays or just chest x-ray to study latent tuberculosis before solid organ transplantation? PMID- 29797689 TI - Electrical stimulation for evoking offset analgesia: A human volunteer methodological study. AB - BACKGROUND: Offset analgesia (OA) is a disproportionally large decrease in the pain perception in response to a small decrease in the stimulation intensity. Traditionally, heat stimulation has been used to evoke OA. The aim of this study was to investigate whether OA could be evoked by electrical stimulation. METHODS: Healthy volunteers (N = 24) underwent two OA-experimental sessions consisting of heat stimuli intensities of 48-49-48 degrees C (traditional OA-paradigm) and electrical stimuli at 150%-180%-150% of the electrical pain perception (EPP) threshold. The three stimuli were delivered for 5 s (STIM1), 5 s (STIM2) and 20 s (STIM3), respectively. The sessions were randomized to the dominant or nondominant volar forearm. Two control sessions were performed with 30 s constantly heat (48 degrees C) and electrical stimuli (150% of the EPP) (CONTROL STIM). In all sessions, the pain intensities were constantly rated on a Visual Analog Scale (VAS, 0-10). RESULTS: Significantly reduced STIM3 VAS ratings as compared to the CONTROL-STIM were reported for heat (1.81 +/- 0.54; p < 0.001) and electrical (2.12 +/- 0.42; p < 0.001) stimuli. The degrees of OA produced by heat and electrical stimuli were similar. A significantly positive correlation was found between thermal and electrical OA-effects (r = 0.48, p < 0.02). CONCLUSIONS: These findings demonstrate that electrical stimulation can elicit significant OA in humans indicating that the peripheral receptors can be bypassed and still evoke OA. Application of the electrical OA model may be of interest for further basic and clinical investigations as a potential new biomarker for central pain inhibition and provide the option to back-translate the technology to animals to understand the underlying neurobiology. SIGNIFICANCE: Electrical stimulation can elicit offset analgesia in humans, indicating that this perceptual modification can be obtained even bypassing peripheral receptors. PMID- 29797690 TI - The role of the Milan System for Reporting Salivary Gland Cytopathology: A 5-year institutional experience. AB - BACKGROUND: Fine-needle aspiration (FNA) is widely accepted in the preoperative management of salivary gland lesions. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) aims to standardize reporting terminology. Studies regarding the risk of malignancy (ROM) for the proposed categories continue to evolve. The current retrospective study applied the MSRSGC to assess ROM for salivary gland lesions and focused on the "indeterminate" categories. METHODS: A total of 627 salivary gland FNA specimens obtained from 2011 through 2016 were retrieved, with follow-up available for 373 cases. The original diagnoses were recategorized using MSRSGC by 2 independent cytopathologists as: 1) non-diagnostic; 2) non-neoplastic; 3) atypia of undetermined significance (AUS); 4a) benign neoplasms; 4b) salivary gland neoplasm of uncertain malignant potential (SUMP); 5) suspicious for malignancy (SFM); and 6) malignant. The ROM and overall ROM for each diagnostic category were determined, with characterization of "indeterminate" (AUS, SUMP, and SFM) lesions. RESULTS: There was near-perfect agreement regarding categorization (626 of 627 cases; 99.8%) between the 2 cytopathologists, with discordance observed for 1 case. The sensitivity, specificity, negative predictive value, and positive predictive value of salivary gland FNA specimens at the study institution were 79%, 98%, 94%, and 92%, respectively. The ROM for non-diagnostic, non-neoplastic, benign neoplasms, AUS, SUMP, SFM, and malignant were 6.7%, 7.1%, 38.9%, 5.0%, 34.2%, 92.9%, and 92.3%, respectively. The indeterminate category had an overall ROM of 47.1%. CONCLUSIONS: The MSRSGC is a valuable tool that can help to standardize reporting and stratify cases preoperatively. Having a better understanding of the indeterminate diagnoses will help further refine risk classification criteria. Cancer Cytopathol 2018. (c) 2018 American Cancer Society. PMID- 29797692 TI - Upper airway obstruction assessment: Peak inspiratory flow and clinical COPD Questionnaire. AB - OBJECTIVES: Spirometric evaluation of upper airway obstruction (UAO) is not commonly performed by Otolaryngologists. In addition, functional evaluation of UAO by flow-volume loops (FVL) is not available in all clinical settings. More recently, peak inspiratory flow (PIF) has proven to be a useful tool to monitor UAO at the patient's bedside. The aim of this work is to assess the role of PIF measured with a simple flow metre (In-Check method) as a standardised, simple, non-invasive tool in quantifying chronic and subacute UAO in a routine clinical practice. In addition, a Clinical COPD Questionnaire (CCQ), previously validated to assess the psychophysical status in patients with laryngotracheal stenosis, was utilised to evaluate respiratory function in UAO. DESIGN: Prospective cohort study. SETTINGS: University teaching hospital. PARTICIPANTS: Seventy 2 subjects, an UAO group of 26 patients and a control group of 46 healthy subjects. MAIN OUTCOME MEASURES: The ability of PIF values to discriminate between the UAO group and the control group was assessed using a ROC curve. A Spearman rank correlation was used to test the relationship between PIF measurements and the global CCQ score. Additionally, an analysis of CCQ at domain and items levels was performed. RESULTS: Peak inspiratory flow values were accurate, with an area under the ROC curve (AUC) of 0.98 (P < .05) for differentiating the control group from the UAO group. A threshold PIF value of 170 L/min was found for diagnosing UAO. An inconclusive negative trend was found (r = -.19; P = .35) between PIF values and CCQ global score. Concerning CCQ, the symptoms domain was the most affected by UAO, higher than mental domains (P < .001) as well as functional domains (P < .01). Exertional dyspnoea and cough were the items that obtained the highest disturbed scores. CONCLUSIONS: Peak inspiratory flow is a non-invasive, quantitative parameter to evaluate the severity of UAO. Testing can be easily performed in a routine clinical setting, with a non-expensive hand-held device, and could help medical follow-up programmes and prevent emergency situations. However, FVL may be necessary for further assessment of UAO diseases. The CCQ confirms that exertional dyspnoea is the main symptom of UAO, but cough remains a common symptom. PMID- 29797694 TI - Continuous N-Hydroxyphthalimide (NHPI)-Mediated Electrochemical Aerobic Oxidation of Benzylic C-H Bonds. AB - Electroorganic chemistry has emerged as an environmentally benign tool for synthetic chemists to achieve efficient transformations that are challenging with traditional reagent-based methods. Continuous flow chemistry brings pharmaceutical industry numerous advantages, but implementing electroorganic synthesis in flow is challenging, especially for electroorganic reactions with coupled electrode reactions and slow chemical reactions. We present a continuous electrolysis system engineered for N-hydroxyphthalimide (NHPI) mediated electrochemical aerobic oxidation of benzylic C-H bonds. First, a cation-exchange membrane prevents the crossover of the NHPI anion from anolyte to catholyte avoiding reductive decomposition of NHPI at the cathode, and enables the usage of a cost-effective reticulated vitreous carbon (RVC) cathode instead of a platinum electrode. Second, running the electrochemical flow cell with recycle streams accommodates the inherently slow kinetics of the chemical reaction without phthalimide-N-oxyl (PINO) radical self-decomposition at the anode, and allows the usage of gaseous oxygen as co-oxidant. PMID- 29797693 TI - A Supramolecular Hydrogel Based on Polyglycerol Dendrimer-Specific Amino Group Recognition. AB - Dendrimer-based supramolecular hydrogels have gained attention in biomedical fields. While biocompatible dendrimers were used to prepare hydrogels via physical and/or chemical crosslinking, smart functions such as pH and molecular control remain undeveloped. Here, we present polyglycerol dendrimer-based supramolecular hydrogel formation induced by a specific interaction between the polyglycerol dendrimer and an amino group of glycol chitosan. Gelation was achieved by mixing the two aqueous solutions. Hydrogel formation was controlled by varying the polyglycerol dendrimer generation. The hydrogel showed pH dependent swelling; strongly acidic conditions induced degradation via dissociation of the specific interaction. It also showed unique l-arginine responsive degradation capability due to competitive exchange of the amino groups of glycol chitosan and l-arginine. These polyglycerol dendrimer-based supramolecular characteristics allow multimodal application in smart biomaterials. PMID- 29797691 TI - Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta-analysis of cytology, HPV testing, and other biomarkers. AB - Anal cancer incidence and mortality have been increasing over the past decade. Although the incidence in the general population remains low, it is much higher in certain subgroups, including those living with human immunodeficiency virus and men who have sex with men. Approximately 90% of anal squamous cell cancers are caused by infection with carcinogenic human papillomavirus (HPV). Given the common etiology between anal and cervical carcinogenesis, screening for anal cancer has been proposed in certain high-risk populations using strategies adapted from cervical cancer prevention. In this review, the authors discuss important differences in anal and cervical cancer regarding the populations at risk, disease natural history, and clinical procedures and outcomes that need to be considered when evaluating strategies for anal cancer screening. They also performed a systematic review and meta-analysis of the performance of anal cytology, anal HPV testing, and various biomarkers for the detection of anal precancers and cancers. The implications of these performance estimates are summarized in the context of risk-based screening and management of anal precancers, and important research gaps are highlighted that need to be addressed to fully understand the benefits and harms of anal cancer screening. Cancer Cytopathol 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. PMID- 29797696 TI - Rapid Quantitative Analysis of Multiple Explosive Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry. AB - A flow-injection analysis tandem mass spectrometry (FIA MSMS) method was developed for rapid quantitative analysis of 10 different inorganic and organic explosives. Performance is optimized by tailoring the ionization method (APCI/ESI), de-clustering potentials, and collision energies for each specific analyte. In doing so, a single instrument can be used to detect urea nitrate, potassium chlorate, 2,4,6-trinitrotoluene, 2,4,6-trinitrophenylmethylnitramine, triacetone triperoxide, hexamethylene triperoxide diamine, pentaerythritol tetranitrate, 1,3,5-trinitroperhydro-1,3,5-triazine, nitroglycerin, and octohy dro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine with sensitivities all in the picogram per milliliter range. In conclusion, FIA APCI/ESI MSMS is a fast (<1 min/sample), sensitive (~pg/mL LOQ), and precise (intraday RSD < 10%) method for trace explosive detection that can play an important role in criminal and attributional forensics, counterterrorism, and environmental protection areas, and has the potential to augment or replace several of the existing explosive detection methods. PMID- 29797695 TI - Theobromine Does Not Affect Fasting and Postprandial HDL Cholesterol Efflux Capacity, While It Decreases Fasting miR-92a Levels in Humans. AB - SCOPE: Chocolate consumption lowers cardiovascular disease risk, which might be attributed to the methylxanthine theobromine. These effects may be mediated through effects on HDL-mediated cholesterol efflux, which may be affected by microRNA (miRNA) levels in the HDL particles. Therefore, the aim of this study is to investigate effects of theobromine consumption on fasting and postprandial cholesterol efflux and miRNAs levels. METHODS AND RESULTS: Thirty overweight and 14 obese healthy men and women participated in this randomized, double-blind crossover study. Participants consumed 500 mg d-1 of theobromine or placebo for 4 weeks. ABCA1-mediated cholesterol efflux was measured using J774 macrophages. MiRNAs levels (miR-92a, miR-223, miR-135a*) were quantified in apolipoprotein B depleted serum. Theobromine consumption did not affect fasting and postprandial cholesterol efflux. Fasting miR-223 and miR-135a levels were unchanged, while miR 92a levels were decreased (-0.21; p < 0.05). The high-fat meal increased postprandial cholesterol efflux capacity (+4.3 percentage points; p <= 0.001), miR-92a (+1.21; p < 0.001), and miR-223 (+1.79; p < 0.001) levels, while a trend was found for miR-135a (+1.08; p = 0.06). CONCLUSION: Theobromine did not improve fasting and postprandial ABCA1-mediated cholesterol efflux capacity, but decreased fasting miR-92a levels. High-fat meal intake increased postprandial cholesterol efflux and the three selected miRNAs levels. PMID- 29797698 TI - An Exceptional Case of Acute Respiratory Failure Caused by Intra-Thoracic Gastric Perforation Secondary to Overeating. AB - An 18-year-old female patient arrived at the emergency department complaining of abdominal pain and fullness after a heavy meal. Physical examination revealed she was filthy and cover in feces, and she experienced severe abdominal distension. She died in ED and a diagnostic autopsy examination was requested. At external examination, the pathologist observed a significant dilation of the anal sphincter and suspected sexual assault, thus alerting the Judicial Authority who assigned the case to our department for a forensic autopsy. During the autopsy, we observed anal orifice expansion without signs of violence; food was found in the pleural cavity. The stomach was hyper-distended and perforated at three different points as well as the diaphragm. The patient was suffering from anorexia nervosa with episodes of overeating followed by manual voiding of her feces from the anal cavity (thus explaining the anal dilatation). The forensic pathologists closed the case as an accidental death. PMID- 29797699 TI - Subtle Alterations in DNA Methylation Patterns in Normal Cells in Response to Dietary Stilbenoids. AB - SCOPE: Searching for correlations between dietary polyphenols and risk of chronic diseases has been a challenge due to the lack of quantitative evaluation methods of long-term exposure. We previously observed substantial DNA methylation changes in human cancer cells upon treatment with polyphenols of the stilbenoid class. When induced in normal cells, such molecular changes may persist and reflect chronic exposure. METHODS AND RESULTS: Illumina 450K microarray is used to delineate a genome wide DNA methylation landscape in MCF10A human immortalized mammary epithelial cells exposed to resveratrol (RSV) at noncytotoxic 15 MUM dose for 9 days. Subtle alterations are observed suggesting remodeling of DNA methylation patterns rather than switch on/off changes. Using pyrosequencing, DNA methylation is quantitatively measured at eight CpG sites located within KCNJ4, RNF169, BCHE, DAOA, HOXA9, RUNX3, KRTAP2-1, and TAGAP, upon exposure to RSV or pterostilbene and shows similar differences induced by both stilbenoids. Two of the probes, Runx3 and Kcnj4, are successfully verified in whole blood DNA from healthy rats on diets supplemented with stilbenoids. CONCLUSIONS: The study provides strong support for testing the utility of polyphenol-mediated changes in DNA methylation as quantitative measures of long-term dietary exposures in nutritional epidemiology and clinical trials. PMID- 29797697 TI - Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC). OBJECTIVES: To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination (IUI). SEARCH METHODS: We searched the following sources from inception to November 2017 to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organization (WHO) clinical trials register and Clinicaltrials.gov. We also searched the references of relevant articles. We did not restrict the searches by language or publication status. SELECTION CRITERIA: We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted the data and assessed risks of bias. We pooled studies where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth and OHSS. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy. We assessed the quality of the evidence for each comparison using GRADE methods. MAIN RESULTS: This is a substantive update of a previous review. We identified 16 additional studies for the 2018 update. We include 42 RCTs (7935 women). The aromatase inhibitor letrozole was used in all studies.Letrozole compared to clomiphene citrate (CC) with or without adjuncts followed by timed intercourseLive birth rates were higher with letrozole (with or without adjuncts) compared to clomiphene citrate (with our without adjuncts) followed by timed intercourse (OR 1.68, 95% CI 1.42 to 1.99; 2954 participants; 13 studies; I2 = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-quality evidence). There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.00; 2536 participants; 12 studies; I2 = 0%; high-quality evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.56, 95% CI 1.37 to 1.78; 4629 participants; 25 studies; I2 = 1%; NNTB = 10; moderate-quality evidence). There is little or no difference between treatment groups in the rate of miscarriage by pregnancy (20% with CC versus 19% with letrozole; OR 0.94, 95% CI 0.70 to 1.26; 1210 participants; 18 studies; I2 = 0%; high-quality evidence) and multiple pregnancy rate (1.7% with CC versus 1.3% with letrozole; OR 0.69, 95% CI 0.41 to 1.16; 3579 participants; 17 studies; I2 = 0%; high-quality evidence). However, a funnel plot showed mild asymmetry, indicating that some studies in favour of clomiphene might be missing.Letrozole compared to laparoscopic ovarian drillingThere is low-quality evidence that live birth rates are similar with letrozole or laparoscopic ovarian drilling (OR 1.38, 95% CI 0.95 to 2.02; 548 participants; 3 studies; I2 = 23%; low-quality evidence). There is insufficient evidence for a difference in OHSS rates (RD 0.00, 95% CI -0.01 to 0.01; 260 participants; 1 study; low-quality evidence). There is low-quality evidence that pregnancy rates are similar (OR 1.28, 95% CI 0.94 to 1.74; 774 participants; 5 studies; I2 = 0%; moderate-quality evidence). There is insufficient evidence for a difference in miscarriage rate by pregnancy (OR 0.66, 95% CI 0.30 to 1.43; 240 participants; 5 studies; I2 = 0%; moderate-quality evidence), or multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 548 participants; 3 studies; I2 = 0%; low-quality evidence).Additional comparisons were made for Letrozole versus placebo, Selective oestrogen receptor modulators (SERMS) followed by intrauterine insemination (IUI), follicle stimulating hormone (FSH), Anastrozole, as well as dosage and administration protocols. There is insufficient evidence for a difference in either group of treatment due to a limited number of studies. Hence more research is necessary. AUTHORS' CONCLUSIONS: Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory polycystic ovary syndrome, compared to clomiphene citrate. There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate. There is high-quality evidence of no difference in miscarriage rates or multiple pregnancy rates. There is low-quality evidence of no difference in live birth and pregnancy rates between letrozole and laparoscopic ovarian drilling, although there were few relevant studies. For the 2018 update, we added good-quality trials, upgrading the quality of the evidence. PMID- 29797701 TI - Suicide by Fatal Pentobarbital Intoxication in Ontario, Canada, from 2012 to 2015. AB - A fatal concentration of pentobarbital found in a coroner's case where the history had not indicated use of this drug prompted a review of fatalities in Ontario from 2012 to 2015. Coroner's case files, including police and toxicology reports, were reviewed in twenty deaths, in which pentobarbital was identified as the primary cause of death. In all of the deaths (11 females, 9 males), the blood concentration of pentobarbital was greater than 10 mg/L. There were three to eight deaths per year and each was classified as suicide. In 11 cases, there was clear evidence that the drug was purchased over the internet from Mexico or China and imported into Canada. In four cases, it appears that the pentobarbital was labeled as a different, innocuous chemical to facilitate crossing the border without scrutiny. The findings underscore the value of a thorough scene investigation, including details of evidence that may be considered unrelated. PMID- 29797700 TI - L-Citrulline Supplementation-Increased Skeletal Muscle PGC-1alpha Expression is Associated With Exercise Performance and Increased Skeletal Muscle Weight. AB - SCOPE: L-citrulline has recently been reported as a more effective supplement for promoting intracellular NO production compared to L-arginine. Here, the effect of L-citrulline on skeletal muscle and its influence on exercise performance were investigated. The underlying mechanism of its effect, specifically on the expression of skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), was also elucidated. METHODS AND RESULTS: Six week-old ICR mice were orally supplemented with L-citrulline (250 mg kg-1 ) daily, and their performance in weight-loaded swimming exercise every other day for 15 days, was evaluated. In addition, mice muscles were weighed and evaluated for the expression of PGC-1alpha and PGC-1alpha-regulated genes. Mice orally supplemented with L-citrulline had significantly higher gastrocnemius and biceps femoris muscle mass. Although not statistically significant, L-citrulline prolonged the swimming time to exhaustion. PGC-1alpha upregulation was associated with vascular endothelial growth factor alpha (VEGFalpha) and insulin-like growth factor 1 (IGF1) upregulation. VEGFalpha and IGF1 are important for angiogenesis and muscle growth, respectively, and are regulated by PGC-1alpha. Treatment with L-NAME, a nitric oxide synthesis inhibitor, suppressed the L-citrulline-induced PGC-1alpha upregulation in-vitro. CONCLUSION: Supplementation with L-citrulline upregulates skeletal muscle PGC-1alpha levels resulting to higher skeletal muscle weight that improves time to exhaustion during exercise. This article is protected by copyright. All rights reserved. PMID- 29797702 TI - Obesity-Associated Diseases Biomarkers Are Differently Modulated in Lean and Obese Individuals and Inversely Correlated to Plasma Polyphenolic Metabolites After 6 Weeks of Mango (Mangifera indica L.) Consumption. AB - SCOPE: Mangos are a rich source of gallotannin-derived polyphenols that may exert anti-inflammatory effects relevant to obesity-related chronic diseases. This randomized human clinical study investigated the influence of daily mango supplementation for 6 weeks on inflammation and metabolic functions in lean and obese individuals. METHODS AND RESULTS: Lean (n = 12, body mass index [BMI] 18 26.2 kg m-2 ) and obese (n = 9, BMI >28.9 kg m-2 ) participants, aged 18-65 years received daily 400 g of mango pulp for 6 weeks. Inflammatory cytokines, metabolic hormones, and lipid profiles were examined in plasma before and after 6 weeks. In lean participants, systolic blood pressure was lowered by 4 mmHg after 6 weeks. In obese participants, hemoglobin A1c (HbA1c) and plasminogen activator inhibitor 1 (PAI-1) were reduced by 18% and 20%, respectively. Obese participants showed decreased plasma concentrations (area under the curve [AUC] 0-8h ) of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1). Correlation analysis indicates that the beneficial effects of mango supplementation on pro inflammatory cytokines, PAI-1 and HbA1c, are associated with systemic exposure to polyphenolic metabolites. CONCLUSIONS: Mango supplementation improves the plasma levels of pro-inflammatory cytokines and metabolic hormones in obese participants. There is a crucial need to investigate the role of lowered polyphenolic absorption in obese individuals on their efficacy in reducing biomarkers for inflammation and other risk factors for chronic diseases. PMID- 29797703 TI - Improving Causal Inferences in Meta-analyses of Longitudinal Studies: Spanking as an Illustration. AB - To evaluate and improve the validity of causal inferences from meta-analyses of longitudinal studies, two adjustments for Time-1 outcome scores and a temporally backwards test are demonstrated. Causal inferences would be supported by robust results across both adjustment methods, distinct from results run backwards. A systematic strategy for evaluating potential confounds is also introduced. The methods are illustrated by assessing the impact of spanking on subsequent externalizing problems (child age: 18 months to 11 years). Significant results indicated a small risk or a small benefit of spanking, depending on the adjustment method. These meta-analytic methods are applicable for research on alternatives to spanking and other developmental science topics. The underlying principles can also improve causal inferences in individual studies. PMID- 29797704 TI - The analgesic effect of a popliteal plexus blockade after total knee arthroplasty: A feasibility study. AB - INTRODUCTION: An obturator nerve block (ONB) and a femoral triangle block (FTB) provide effective analgesia after total knee arthroplasty (TKA) without impeding the ambulation, although the ONB produces motor blockade of the hip adductor muscles. The popliteal plexus (PP) in the popliteal fossa is formed by contribution from the tibial nerve and the posterior obturator nerve, innervating intraarticular genicular structures and the posterior capsule of the knee. We hypothesised that a popliteal plexus block (PPB) as a supplement to an FTB would reduce pain after TKA without anaesthetising motor branches from the sciatic nerve in the popliteal fossa. AIM: To assess the analgesic effect of adding a PPB to an FTB in 10 subjects with significant pain after TKA. METHODS: All subjects underwent unilateral TKA with spinal anaesthesia and received an FTB. The cutaneous sensation and the postoperative pain were assessed. The primary outcome was the proportion of subjects with pain above numeric rating scale (NRS) 3 followed by a reduction to NRS 3 or below after conducting a PPB. RESULTS: Ten subjects with a median pain of NRS 5.5 (interquartile range [IQR] 4-8) after unilateral TKA received a PPB. All 10 subjects experienced a reduction in pain to NRS 3 or below (NRS 1.5 [IQR 0-3]) within a mean time of 8.5 (95% CI 6.8-10.2) minutes. Three subjects were completely pain free after the PPB. The ankle muscle strength was not affected. CONCLUSIONS: The PPB provided effective pain relief without affecting the ankle muscle strength in all 10 subjects with significant pain after TKA and an FTB. PMID- 29797705 TI - Characteristics of jugular bulb oxygen saturation in patients after cardiac arrest: A prospective study. AB - BACKGROUND: Using cerebral oxygen venous saturation post-cardiac arrest (CA) is limited because of a small sample size and prior to establishment of target temperature management (TTM). We aimed to describe variations in jugular bulb oxygen saturation during intensive care in relation to neurological outcome at 6 months post- CA in cases where TTM 33 degrees C was applied. METHOD: Prospective observational study in patients over 18 years, comatose immediately after resuscitation from CA. Patients were treated with TTM 33 degrees C M and received a jugular bulb catheter within the first 26 hours post-CA. Neurological outcome was assessed at 6 months using the Cerebral Performance Categories (CPC) and dichotomized into good (CPC 1-2) and poor outcome (CPC 3-5). RESULTS: Seventy five patients were included and 37 (49%) patients survived with a good outcome at 6 months post-CA. No differences were found between patients with good outcome and poor outcome in jugular bulb oxygen saturation. Higher values were seen in differences in oxygen content between central venous oxygen saturation and jugular bulb oxygen saturation in patients with good outcome compared to patients with poor outcome at 6 hours (12 [8-21] vs 5 [-0.3 to 11]% P = .001) post-CA. Oxygen extraction fraction from the brain illustrated lower values in patients with poor outcome compared to patients with good outcome at 96 hours (14 [9-23] vs 31 [25-34]% P = .008). CONCLUSIONS: Oxygen delivery and extraction differed in patients with a good outcome compared to those with a poor outcome at single time points. Based on the present findings, the usefulness of jugular bulb oxygen saturation for prognostic purposes is uncertain in patients treated with TTM 33 degrees C post-CA. PMID- 29797706 TI - Risk factors for cardiopulmonary resuscitation-related injuries sustained during out-of-hospital cardiac arrests. AB - BACKGROUND: We aimed to determine the incidence of and associated risk factors for cardiopulmonary resuscitation (CPR)-related injuries in non-survivors of out of-hospital cardiac arrests (OHCAs) in an emergency medical service (EMS) system in which all CPR procedures are performed on scene and patients are not routinely transported to the hospital with ongoing CPR. MATERIAL AND METHODS: We conducted this prospective observational study between 1 June 2013, and 31 May 2014. Data were collected from EMS datasheets and forensic autopsy records. The exclusion criteria were OHCAs due to trauma in the thoracic or abdominal area. EMS adhered to the European Resuscitation Council Resuscitation Guidelines (2010) during the resuscitation attempts. RESULTS: Emergency medical service provided CPR in 280 attended OHCAs with 207 cases terminated on scene. A total of 149 patients underwent a forensic autopsy and 47% had a CPR-related injury. The most common injuries were multiple rib fractures (43%), with 22% of patients having more than eight fractured ribs. Abdominal visceral injuries or injuries related to airway management were rare. The injuries were associated with older age, male gender, initial shockable rhythm and public location of the cardiac arrest (P < .05 respectively). In the multivariable regression analysis, older age, male gender, and public location were independent predictors for injuries. There were no differences in the durations of the CPR attempt between the injured and non injured groups. CONCLUSION: Older age, male gender, and public location were independently associated with CPR-related injuries. The duration of the resuscitation attempts did not affect the incident of injuries. PMID- 29797707 TI - High-resolution x-ray tomographic morphological characterisation of electrospun nanofibrous bundles for tendon and ligament regeneration and replacement. AB - Repair of ligaments and tendons requires scaffolds mimicking the spatial organisation of collagen in the natural tissue. Electrospinning is a promising technique to produce nanofibres of both resorbable and biostable polymers with desired structural and morphological features. The aim of this study was to perform high-resolution x-ray tomography (XCT) scans of bundles of Nylon6.6, pure PLLA and PLLA-Collagen blends, where the nanofibres were meant to have a predominant direction. Characterisation was carried out via a dedicated methodology to firmly hold the specimen during the scan and a workflow to quantify the directionality of the nanofibres in the bundle. XCT scans with 0.4 and 1.0 MUm voxel size were successfully collected for all bundle compositions. Better image quality was achieved for those bundles formed by thicker nanofibres (i.e. 0.59 MUm for pure PLLA), whereas partial volume effect was more pronounced for thinner nanofibres (i.e. 0.26 MUm for Nylon6.6). As expected, the nanofibres had a predominant orientation along the axis of the bundles (more than 20% of the nanofibres within 3 degrees and more than 60% within 18 degrees from the bundle axis), with a Gaussian-like dispersion in the other directions. The directionality assessment was validated by comparison against a similar analysis performed on SEM images: the XCT analysis overestimated the amount of nanofibres very close to the bundle axis, especially for the materials with thinnest nanofibres, but adequately identified the amount of nanofibres within 12 degrees . LAY DESCRIPTION: Repair of ligaments and tendons requires dedicated materials (scaffolds) mimicking the spatial organisation of the collagen (the main material composing such natural tissue). Electrospinning is a promising technique that allows production of fibres with nanometric dimension using high voltage to stretch very tiny drops of polymeric solutions. Electrospinning allows processing both polymers that can be resorbed by the host tissue, and nonresorbable ones, to obtain the desired structural and morphological features by arranging the nanofibres in bundles. The aim of this study was to perform high-resolution x-ray computed tomography (XCT) scans of bundles, where the nanofibres were meant to have a predominant direction. The investigation included bundles of different compositions: a biostable polymer (Nylon) and bioresorbable ones (pure Poly-L lactic acid (PLLA) and PLLA-Collagen blends). The electrospun bundles were produced using a validated method (Sensini et al 2017: https://doi.org/10.1088/1758-5090/aa6204). To this end, we developed a dedicated methodology to scan such small specimens, and a workflow to quantify the directionality of the nanofibres in the bundle. For all the compositions, XCT scans with extremely high resolution (i.e. down to 0.4 MUm) were successfully collected. As expected, better images were obtained for those bundles where the nanofibres were thicker than the scanning resolution (i.e. 0.59 MUm for pure PLLA). The images of the thinnest nanofibres (i.e. 0.26 MUm for Nylon) were poorer because the fibre diameter was smaller than the resolution (partial volume effect). The nanofibres had a predominant orientation along the axis of the bundles (more than 60% of the nanofibres were within 18 degrees from the bundle axis). The nanofibres had a Gaussian-like dispersion in the other directions. As this is the first time that XCT is used to quantify the directionality of this kind of bundles, the directionality assessment was further validated by comparison against a similar analysis performed on SEM images. Overall, this study has demonstrated the usefulness and reliability of using high-resolution x ray computed tomography (XCT) scans to investigate the morphology of polymeric scaffolds made of electrospun nanofibres. PMID- 29797708 TI - Building a Workforce for Future Health Systems: Reflections from Health Policy and Systems Research. AB - INTRODUCTION: The era of the Sustainable Development Goals calls for multidisciplinary research and intersectoral approaches to addressing health challenges. This presents a unique opportunity for multidisciplinary fields concerned with complex systems. Those working in system-oriented fields such as health policy and systems research (HPSR) and health services research must be forward-thinking in optimizing their collective ability to address these global challenges. OBJECTIVES: The objective of this commentary was to share reflections on challenges and strategies in managing the HPSR workforce in order to stimulate dialogue and cross-learning across similar fields. STRATEGIES/FINDINGS: The following strategies are discussed here: definitional clarity of expected competencies and coordination across HPS researchers, national investment in HPSR, institutional capacity for coproduction of knowledge across different types of actors, and participatory leadership. CONCLUSIONS: Creative approaches in training, financing, developing, and leading the diverse workforce required to strengthen health systems can pave the way for its full-time and part-time members to work together. PMID- 29797709 TI - Systematic overview and critical appraisal of meta-analyses of interventions in intensive care medicine. AB - RATIONALE: Meta-analysed intervention effect estimates are perceived to represent the highest level of evidence. However, such effects and the randomized clinical trials which are included in them need critical appraisal before the effects can be trusted. OBJECTIVE: Critical appraisal of a predefined set of all meta analyses on interventions in intensive care medicine to assess their quality and assessed the risks of bias in those meta-analyses having the best quality. METHODS: We conducted a systematic search to select all meta-analyses of randomized clinical trials on interventions used in intensive care medicine. Selected meta-analyses were critically appraised for basic scientific criteria, (1) presence of an available protocol, (2) report of a full search strategy, and (3) use of any bias risk assessment of included trials. All meta-analyses which qualified these criteria were scrutinized by full "Risk of Bias in Systematic Reviews" ROBIS evaluation of 4 domains of risks of bias, and a "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" PRISMA evaluation. RESULTS: We identified 467 meta-analyses. A total of 56 meta-analyses complied with these basic scientific criteria. We scrutinized the risks of bias in the 56 meta-analyses by full ROBIS evaluation and a PRISMA evaluation. Only 4 meta analyses scored low risk of bias in all the 4 ROBIS domains and 41 meta-analyses reported all 27 items of the PRISMA checklist. CONCLUSION: In contrast with what might be perceived as the highest level of evidence only 0.9% of all meta analyses were judged to have overall low risk of bias. PMID- 29797710 TI - The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study. AB - BACKGROUND: Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. METHODS: We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. RESULTS: A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). CONCLUSION: Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment. PMID- 29797712 TI - Analysis of preventable deaths and errors in trauma care in a Scandinavian trauma level-I centre. AB - BACKGROUND: The wide disparity in the methodology of preventable death analysis has created a lack of comparability among previous studies. The guidelines for the peer review (PR) procedure suggest the inclusion of risk-adjustment methods to identify patients to review, that is, exclude non-preventable deaths (probability of survival [Ps] < 25%) or focus on preventable deaths (Ps > 50%). We aimed to, through PR process, (1) identify preventable death and errors committed in a level-I trauma centre, and (2) explore the use of different risk adjustment methods as a complement. METHODS: A multidisciplinary committee reviewed all trauma patients, which died a trauma-related death, within 30 days of admission to Karolinska University Hospital, Stockholm, in the period of 2012 2016. Ps was calculated according to TRISS and NORMIT and their accuracy where compared. RESULTS: Two hundred and ninety-eight deaths were identified and 252 were reviewed. The majority of deaths occurred between 1 and 7 days. Ten deaths (4.0%) were classified as preventable. Sixty-seven errors were identified in 53 (21.0%) deaths. The most common error was inappropriate treatment in all deaths (21 of 67) and in preventable deaths (5 of 13). Median Ps in non-preventable deaths was higher than the cut-off (<25%) and Ps-TRISS was almost twice as high as Ps-NORMIT (65% vs 33%, P < .001). Two clinically judged preventable deaths with Ps <25% would have been missed with both models. Median Ps in preventable deaths was above the cut-off (>50%) and higher with Ps-TRISS vs Ps-NORMIT (75% vs 58%, P < .001). Three and 4 clinically judged preventable deaths would have been missed, respectively, for TRISS and NORMIT, if using this cut-off. CONCLUSION: Preventable deaths were commonly caused by clinical judgment errors in the early phases but death occurred late. Ps calculated with NORMIT was more accurate than TRISS in predicting mortality, but both perform poorly in identifying preventable and non-preventable deaths when applying the cut-offs. PR of all trauma death is still the golden standard in preventability analysis. PMID- 29797711 TI - Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden - Outlier or predecessor? AB - OBJECTIVES: Off-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis. MATERIAL AND METHODS: Review of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6 years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital. RESULTS: Presently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%. CONCLUSIONS: The share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly. PMID- 29797713 TI - Syringes versus Chinese cups in harvesting suction-induced blister graft: a randomized split-body study. AB - BACKGROUND: Suction blister grafting (SBG) is a technique where the pigmented epidermis is harvested from the donor site by induction of a blister using different suction methods as syringes, Chinese cups, suction device, etc. However, pain, time consumption, incomplete blister formation, and failure of blister development are the main limitations. OBJECTIVE: To compare between cups and syringes of similar diameter in inducing suction blisters. PATIENTS AND METHODS: In 30 patients with stable nonsegmental vitiligo, 2-cm-diameter (20 ml) syringe was applied on the anterolateral aspect of one thigh and a 2-cm-diameter cup on the corresponding site of the other thigh where right and left sides were chosen randomly. Patients were observed untill complete blister development or for a maximum of 3 hours. Suction blister induction time (SBIT) and the blister diameter were recorded for each patient. Pain during the process of induction was evaluated. RESULTS: Incomplete blister development was noted in 9 out of 30 (30%) with 2 cm syringes and 6 out of 30 (20%) with the similar diameter cups with no significant difference (P = 0.49). No significant difference was found between SBIT induced by the 2 cm syringes and the similar size cups (101.17 +/- 68.14 minutes, 98 +/- 56.84 minutes, respectively) (P = 0.85). Meanwhile, blister diameter induced by either syringe or cup was not significantly different (P = 0.37). Anesthesia was for short duration with xylocaine, and pain was intolerable in both sides in the first seven patients. A combination of xylocaine and bupivacaine was used with prolonged loss of pain in 17 of the remaining 23 patients and tolerable pain in six patients similarly in both sides. CONCLUSION: According to present results, the differences in SIBT, diameter of blisters, and number of complete blister formation induced by either syringes or cups of similar size were not significant. Therefore, whatever the available and feasible technique for the surgeon will be the ideal choice. A combination of xylocaine and bupivacaine is recommended to overcome the accompanying pain of the procedure. PMID- 29797714 TI - Corticosteroids and risk of gastrointestinal bleeding in critically ill adults: Protocol for a systematic review. AB - BACKGROUND: Corticosteroids are frequently prescribed to critically ill patients. However, their use may increase the risk of gastrointestinal (GI) bleeding, which is associated with morbidity and mortality. Accordingly, we aim to assess whether continued administration of corticosteroids for >24 hours increases the rate of GI bleeding in adult critically ill patients compared to placebo or no treatment. METHODS/DESIGN: We will conduct a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. The participants will be adult (as defined in the included trials) critically ill patients. The intervention will be any corticosteroid administered systematically for >24 hours and the comparator will be placebo or no treatment. The primary outcome will be rate of clinically important GI bleeding. We will systematically search EMBASE, MEDLINE, Medline In-Process, Cochrane Library, Epistemonikos and trial registries for relevant literature, as well as perform a hand search. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: The risk of GI bleeding in adult critically ill patients treated with corticosteroids is unknown. Hence, there is need for a robust systematic review to assess this risk and provide clinicians with a clearer understanding of the strength and limitations of existing data. PMID- 29797715 TI - Diagnostic accuracy of ultrasound in detecting the depth of invasion in women at risk of abnormally invasive placenta: A prospective longitudinal study. AB - INTRODUCTION: The aim of this study was to assess the diagnostic accuracy of ultrasound in detecting the depth of abnormally invasive placenta in women at risk. MATERIAL AND METHODS: Prospective longitudinal study including women with placenta previa and at least one prior cesarean delivery or uterine surgery. Depth of abnormally invasive placenta was defined as the degree of trophoblastic invasion through the myometrium and was assessed with histopathological analysis. The ultrasound signs explored were: loss of clear zone, placental lacunae, bladder wall interruption, uterovesical hypervascularity, and increased vascularity in the parametrial region. RESULTS: In all, 210 women were included in the analysis. When using at least one sign, ultrasound had an overall sensitivity of 100% (95% CI 96.5-100) and overall specificity of 61.9 (95% CI 51.9-71.2) for all types of abnormally invasive placenta. Using two ultrasound signs increased the diagnostic accuracy in terms of specificity (100%, 95% CI 96.5-100) but did not affect sensitivity. When stratifying the analysis according to the depth of placental invasion, using at least one sign had a sensitivity of 100% (95% CI 93.7-100) and 100% (95% CI 92.6-100) for placenta accreta/increta and percreta, respectively. Using three ultrasound signs improved the detection rate for placenta percreta with a sensitivity of 100% (95% CI 92.6-100) and a specificity of 77.2% (95% CI 69.9-83.4). CONCLUSION: Ultrasound has a high diagnostic accuracy in detecting the depth of placental invasion when applied to a population with specific risk factors for anomalies such as placenta previa and prior cesarean delivery or uterine surgery. PMID- 29797717 TI - Flexion decreases the ventilation quality of the Ambu(r) AuraGainTM laryngeal mask in paralysed children: A prospective randomised crossover study. AB - BACKGROUND: The influence of different head and neck positions on ventilation with the Ambu(r) AuraGainTM remains unevaluated in children. This study assessed the influence of different head and neck positions on ventilation with the AuraGainTM in paediatric patients. METHODS: In this prospective, randomised crossover study, children <=7 years of age who were scheduled for elective surgery under general anaesthesia were enrolled. An AuraGainTM was placed in all patients; mechanical ventilation was performed using a volume-controlled mode with a tidal volume of 10 mL/kg. Respiratory rate was adjusted to maintain a ET CO2 of 35-40 mm Hg. The oropharyngeal leak pressure, expiratory tidal volume, peak inspiratory pressure, ventilation score and fibreoptic bronchoscopic view score were assessed for the neutral head and neck position, and then for the flexed, extended and rotated head and neck positions in a random order. RESULTS: Compared with the neutral position, the oropharyngeal leak pressure increased in the flexed position (P < .001), and decreased in the extended (P = .014) and rotated position (P = .002). The expiratory tidal volume and ventilation score were significantly reduced during flexion (all P < .005), and were comparable among the neutral, extended and rotated positions. The fibreoptic score improved in the extended and rotated position (all P < .001). Only the flexion ventilation score was lower compared with the neutral position (P = .014). CONCLUSIONS: Clinically, the flexed head and neck positions negatively affected ventilation due to obstruction of the airway. Ventilation with AuraGainTM can be effectively performed with the head and neck in the neutral, extended and rotated position in paediatric patients. PMID- 29797716 TI - Accuracy of 12-hour urine collection in the diagnosis of pre-eclampsia. AB - OBJECTIVE: To evaluate the accuracy of a 12-hour urine collection to diagnose pre eclampsia and to determine whether time of collection influences the performance of this test. METHODS: A prospective observational study was conducted in a tertiary obstetric center in Portugal between November 1, 2015, and November 30, 2016. Pregnant women (>=20 weeks) admitted for observation with suspected pre eclampsia were eligible for inclusion. Two consecutive 12-hour urine samples were collected (07:00-19:00 hours vs 19:00-07:00 hours). Protein levels were measured in each 12-hour sample, as well as in a pooled sample (07:00-07:00 hours). The diagnostic cut-off values for pre-eclampsia were 150 mg (12-hour samples) and 300 mg (24-hour sample). RESULTS: The study included 99 patients and diagnoses of pre eclampsia were confirmed among 42 (42%) patients. In all, 456 12-hour urine samples were analyzed (equivalent to 228 24-hour samples). Qualitative analysis (pre-eclampsia vs no pre-eclampsia) indicated substantial agreement between the 12- and 24-hour samples (Cohen kappa 0.779). The sensitivity was 85.9% (95% confidence interval [CI] 81%-90%) and the specificity was 91.7% (95% CI 88%-95%). No statistically significant difference was found between the two 12-hour collections. CONCLUSION: The 12-hour test showed acceptable accuracy for detecting pre-eclampsia, regardless of the time of collection. PMID- 29797718 TI - A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities. AB - Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules MUm-2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules MUm-2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1. PMID- 29797719 TI - Immunological and microbiological periodontal profiles in isolated growth hormone deficiency. AB - BACKGROUND: Growth hormone (GH) has been identified as an important regulator of the immune response. We have previously shown that adults with isolated GH deficiency (IGHD) due to a mutation in the GH releasing hormone receptor (GHRHR) gene, have a greater chance of having periodontitis. However, the interaction of GH with periodontal tissues is still unknown, and this population has emerged as a unique model to investigate this issue. Therefore, we evaluated the microbiological and immunological periodontal profiles of such individuals. METHODS: Nineteen IGHD and 19 controls matched by age, sex, diabetes, and smoking status, were enrolled in this case-control study. Periodontal clinical parameters (probing depth [PD] and clinical attachment loss [AL]) were measured at six sites per tooth. Immune mediators (C-reactive protein, matrix metalloproteinase [MMP] 8, MMP-9, interleukin [IL]-1alpha, IL-6, IL-8, tumor necrosis factor [TNF]-alpha, adiponectin, and leptin) were analyzed by enzyme-linked immunosorbent assay (ELISA) in the gingival crevicular fluid (GCF) in four non-adjacent sites for each participant (two with PD <=3 mm [shallow sites] and two with PD >=7 mm or the worst PD found in the mouth [deep sites]). Bacterial quantification (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) of subgingival biofilm samples collected from these same sites was performed by quantitative real-time polymerase chain reaction (qPCR). RESULTS: IGHD individuals presented higher values of PD and AL, and increased levels of CRP, IL-8, MMP-8, and adiponectin in the GCF. Bacterial quantification did not identify differences between the two groups. CONCLUSION: IGHD alters the local immune response in periodontal pockets leading to greater attachment loss, and GH stands out as an important hormone to be evaluated in the pathogenesis of periodontitis. PMID- 29797720 TI - Comparison of three commercially available buffy coat pooling sets for the preparation of platelet concentrates. AB - BACKGROUND: A disposable set for platelet concentrate (PC) preparation by the buffy coat method allows pooling of buffy coats, centrifugation and cell separation with in-line leucocyte filtration. This study compares three commercially available pooling sets in combination with INTERCEPT pathogen inactivation (PI). MATERIALS AND METHODS: Sets for pooling of buffy coats were from Fresenius Kabi (FRE), Macopharma (MAC) and Terumo BCT (TER). Platelet yield, recovery and concentration were compared before and after PI (n = 20). Platelet quality was assessed by annexin V binding, P-selectin expression and PAC1 binding. RESULTS: The TER pooling set had the highest platelet yield (5.39 +/- 0.44 * 1011 ) compared with MAC (4.53 +/- 0.77) and FRE (4.56 +/- 0.51) prior to PI. This was the result of a significantly higher platelet concentration in the TER storage bag (1.41 +/- 0.12 * 106 /MUL) compared with MAC (1.18 +/- 0.19) and FRE (1.28 +/- 0.15). However, the TER platelet content decreased by 15.6% after PI, yielding 4.55 +/- 0.47 * 1011 platelets compared with smaller reductions at 9.5% for MAC (4.10 +/- 0.69) and 4.4% for FRE (4.36 +/- 0.52). None of the individual PC contained >106 leucocytes. The pH in TER PC was lower compared with MAC and FRE caused by a higher lactic acid production rate. Consequently, PAC1 binding after TRAP activation was lowest for TER PC on day 6. P-selectin and annexin V were not different between suppliers. CONCLUSION: This study demonstrates the added value of evaluating the entire component production process when introducing a new consumable. This study helped to inform a decision on what pooling set is ideally suited for routine implementation taking into account PI. PMID- 29797721 TI - Postoperative infections after dental implant placement: Variables associated with increased risk of failure. AB - BACKGROUND: Wound infections after dental implant placement are a rare finding that might lead to early implant failure. However, the available information on this topic is scarce. METHODS: This retrospective cohort study was conducted to determine factors that may increase the failure rate of dental implants that presented a postoperative infection during the osseointegration period. Postoperative infections were defined as the presence of pus or fistula in the surgical area, with pain or tenderness, swelling, redness, and heat or fever, before prosthetic loading. A bivariate and multivariate analysis of the data using Cox proportional-hazards regression was performed to detect prognostic factors for implant failure in patients that suffer infections. RESULTS: The patient-based prevalence of postoperative infections after implant placement was 2.80% (95% confidence interval (95%CI): 2.04% to 3.83%). Thirty-three out of 37 (89.19%) patients with infections had to be surgically retreated because of antibiotic failure and 65% of the infected implants were removed. The bivariate analysis showed a significant association between implant failure and the collar surface (HR: 3.12; 95% CI: 1.16 to 8.41; P = 0.014). Cox proportional-hazards regression indicated that rough-surfaced collars increased 2.35 times the likelihood of failure (95% CI: 0.87 to 6.37; P = 0.071). CONCLUSIONS: The survival of implants placed in the maxilla, with smooth collar, and late-onset of infection was higher than those placed in the mandible, with a rough collar and early onset of infection. In general, signs of infection after dental implant placement compromises the survival rate of the affected fixtures. PMID- 29797724 TI - The behaviour and perception of illness: modulating variables of adherence in patients with haemophilia. AB - BACKGROUND: The recommended treatment in patients with severe haemophilia is prophylaxis. This prevents bleedings and reduces or delays the haemophilic arthropathy. Adherence defined as the follow-up of the patient to the prescriptions of the health professional to his treatment, both pharmacological and modifications in habits or stylelifes. Adherence rates in haemophilia are better than in other chronic diseases, but there remain reasons for nonadherence. The aim was to see if disease behaviour and disease perception together with coping strategies modulate adherence to treatment. MATERIAL AND METHODS: Multicenter cross-sectional descriptive study. Patients recruited in Units of Hemophilia Hospitals and Regional Haemophilia Associations. Twenty-three patients participated The instruments used are as follows: data sheet, SF-36, A36 Hemophilia-Qol, Illness Perception Questionnaire-Revised (IPQ-R), Illness Behavior Questionnaire (IBQ) and Coping Strategies Inventory (CSI) and VERITAS Pro. RESULTS: We found that 56% of patients with haemophilia are adherent. The most relevant clinical variables were hemarthrosis, diagnosis of arthropathy and presence of any coinfection, as well as family history, labour status and sociodemographic variables. Age was not a relevant variable in adherence. The worst adherence coincides with poorer quality of life and inadequate coping style. Nonadherent patients show greater conviction of disease, perception of cyclicity, more hypochondriacal behaviour towards the illness and perception concern about possible side effects of medication. CONCLUSION: Adherence in haemophilia requires a more experiential approach and individualized education. It is important that professionals take into account the patient's perception, behaviour and attitude towards the disease to achieve a better adaptation of their coping resources. PMID- 29797722 TI - Arabidopsis Lunapark proteins are involved in ER cisternae formation. AB - The plant endoplasmic reticulum (ER) is crucial to the maintenance of cellular homeostasis. The ER consists of a dynamic and continuously remodelling network of tubules and cisternae. Several conserved membrane proteins have been implicated in formation and maintenance of the ER network in plants, such as RHD3 and the reticulon proteins. Despite the recent work in mammalian and yeast cells, the detailed molecular mechanisms of ER network organization in plants remain largely unknown. Recently, novel ER network-shaping proteins called Lunapark (LNP) have been identified in yeast and mammalian cells. Here we identify two Arabidopsis LNP homologues and investigate their subcellular localization via confocal microscopy and potential function in shaping the ER network using protein-protein interaction assays and mutant analysis. We show that AtLNP1 overexpression in tobacco leaf epidermal cells mainly labels cisternae in the ER network, whereas AtLNP2 labels the whole ER. Overexpression of LNP proteins results in an increased abundance of ER cisternae and lnp1 and lnp1lnp2 amiRNA lines display a reduction in cisternae and larger polygonal areas. Thus, we hypothesize that AtLNP1 and AtLNP2 are involved in determining the network morphology of the plant ER, possibly by regulating the formation of ER cisternae. PMID- 29797725 TI - Comparison of sensory perception and verbal expression of Korean Kimchi stews between Chinese consumers and Korean trained panelists. AB - BACKGROUND: Sensory drivers of liking in foreign food markets are difficult to identify because the expression of perceived characteristics varies depending on cultural differences. We aimed to identify differences in the perception and expression of a Korean home meal replacement product (Kimchi stew) between 10 Korean trained panelists versus 50 eastern Chinese consumers (EC) and 54 northern Chinese consumers (NC) using descriptive analysis and rate-all-that-apply (RATA) tests. Regional differences between the EC and NC groups were also investigated. RESULTS: Sensory representations of the six Kimchi stew samples were similar between the Korean trained and Chinese consumer panels. Use of simple sensory RATA terms was similar among the groups. However, EC, who have a daily diet with mild flavors, associated consumer terms with negative connotations, such as odd flavor and sharp, with burning sensation and seasoning, implying the influence of regional food cultures. CONCLUSION: RATA could elicit foreign consumers' sensory representations of an unfamiliar ethnic food that was comparable to that from descriptive analysis, assisting researchers in understanding target consumers' sensory perceptions in a more cost- and time-effective manner. The inclusion of consumer terms in a RATA list and its correlation with descriptive analysis by a native descriptive panel can help with the understanding of foreign consumers' verbal expressions. (c) 2018 Society of Chemical Industry. PMID- 29797723 TI - Effect of neuromuscular electrical stimulation frequency on muscles of the tongue. AB - INTRODUCTION: Neuromuscular electrical stimulation (NMES) for the treatment of swallowing disorders is delivered at a variety of stimulation frequencies. We examined the effects of stimulation frequency on tongue muscle plasticity in an aging rat model. METHODS: Eighty-six young, middle-aged, and old rats were assigned to either bilateral hypoglossal nerve stimulation at 10 or 100 Hz (5 days/week, 8 weeks), sham, or no-implantation conditions. Muscle contractile properties and myosin heavy chain (MyHC) composition were determined for hyoglossus (HG) and styloglossus (SG) muscles. RESULTS: Eight weeks of 100-Hz stimulation resulted in the greatest changes in muscle contractile function with significantly longer contraction and half-decay times, the greatest reduction in fatigue, and a transition toward slowly contracting, fatigue-resistant MyHC isoforms. DISCUSSION: NMES at 100-Hz induced considerable changes in contractile and phenotypic profiles of HG and SG muscles, suggesting higher frequency NMES may yield a greater therapeutic effect. Muscle Nerve, 2018. PMID- 29797726 TI - Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats. AB - KEY POINTS: Essential hypertension is associated with hyperactivity of the sympathetic nervous system and hypoperfusion of the brainstem area controlling arterial pressure. Sympathetic and parasympathetic innervation of vertebrobasilar arteries may regulate blood perfusion to the brainstem. We examined the autonomic innervation of these arteries in pre-hypertensive (PHSH) and hypertensive spontaneously hypertensive (SH) rats relative to age-matched Wistar rats. Our main findings were: (1) an unexpected decrease in noradrenergic sympathetic innervation in PHSH and SH compared to Wistar rats despite elevated sympathetic drive in PHSH rats; (2) a dramatic deficit in cholinergic and peptidergic parasympathetic innervation in PHSH and SH compared to Wistar rats; and (3) denervation of sympathetic fibres did not alter vertebrobasilar artery morphology or arterial pressure. Our results support a compromised vasodilatory capacity in PHSH and SH rats compared to Wistar rats, which may explain their hypoperfused brainstem. ABSTRACT: Neurogenic hypertension may result from brainstem hypoperfusion. We previously found remodelling (decreased lumen, increased wall thickness) in vertebrobasilar arteries of juvenile, pre-hypertensive spontaneously hypertensive (PHSH) and adult spontaneously hypertensive (SH) rats compared to age-matched normotensive rats. We tested the hypothesis that there would be a greater density of sympathetic to parasympathetic innervation of vertebrobasilar arteries in SH versus Wistar rats irrespective of the stage of development and that sympathetic denervation (ablation of the superior cervical ganglia bilaterally) would reverse the remodelling and lower blood pressure. Contrary to our hypothesis, immunohistochemistry revealed a decrease in the innervation density of noradrenergic sympathetic fibres in adult SH rats (P < 0.01) compared to Wistar rats. Unexpectedly, there was a 65% deficit in parasympathetic fibres, as assessed by both vesicular acetylcholine transporter (alpha-VAChT) and vasoactive intestinal peptide (alpha-VIP) immunofluorescence (P < 0.002) in PHSH rats compared to age-matched Wistar rats. Although the neural activity of the internal cervical sympathetic branch, which innervates the vertebrobasilar arteries, was higher in PHSH relative to Wistar rats, its denervation had no effect on the vertebrobasilar artery morphology or persistent effect on arterial pressure in SH rats. Our neuroanatomic and functional data do not support a role for sympathetic nerves in remodelling of the vertebrobasilar artery wall in PHSH or SH rats. The remodelling of vertebrobasilar arteries and the elevated activity in the internal cervical sympathetic nerve coupled with their reduced parasympathetic innervation suggests a compromised vasodilatory capacity in PHSH and SH rats that could explain their brainstem hypoperfusion. PMID- 29797727 TI - Severe anemia associated with increased risk of death and myocardial ischemia in patients declining blood transfusion. AB - BACKGROUND: There are limited data on morbidity and mortality in severely anemic patients for whom blood transfusion is not an option, with most data coming only from surgical patients and no data on the rate of myocardial ischemia associated with severe anemia. We sought to determine rates of all-cause mortality and myocardial ischemia in severely anemic hospitalized patients declining transfusion. STUDY DESIGN AND METHODS: With institutional review board approval, we conducted a retrospective review of all hospital admissions for adult blood refusal patients between January 2004 and September 2015 at a single institution. Severe anemia was defined as hemoglobin (Hb) level of not more than 8.0 g/dL at any time during hospital admission. Outcomes measured included all-cause mortality within 30 days of nadir Hb and myocardial ischemia as defined by abnormal troponin (>0.10 ng/mL). We studied the association of patient's nadir Hb with outcomes via multivariable repeated measures generalized estimating equations (GEEs). RESULTS: Of 1306 blood refusal patients with hospital admissions during the study period, 263 had at least one admission with Hb level of not more than 8.0 g/dL. The rate of all-cause mortality within 30 days was 19.8%, and the multivariable GEE model indicated a 55% increase in odds of mortality per 1 g/dL decrease in nadir Hb (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.25-1.91; p < 0.0001). Rate of myocardial ischemia was 10.5% and in the multivariable model risk increased with decreasing nadir Hb (per 1 g/dL decrease; OR, 1.42; 95% CI, 1.07-1.90; p = 0.016). CONCLUSIONS: Severe anemia is associated with increased myocardial ischemia and mortality in patients declining transfusion, with risk increasing with decreasing nadir Hb. PMID- 29797728 TI - Effect of radio-frequency heating on microbial load, flavor, color, and texture profiles of Cordyceps militaris. AB - BACKGROUND: Cordyceps militaris is a medicine and food dual-purpose mushroom extensively cultivated and consumed in East and Southeast Asia for centuries. However, it has an extremely short shelf life of 3-4 days at room temperature. C. militaris was pasteurized for 10, 20, and 30 min by radio-frequency (RF) at an electrode gap of 20 mm. The effect of RF heating on the microbial load, color, texture, and flavor attributes of C. militaris was evaluated and compared with those sterilized by conventional high-pressure steam. RESULTS: RF heating contributed to good heating uniformity, uniform temperature distribution, and significant decrease in total microbial load. C. militaris heated by RF exhibited unnoticeable total color difference compared with unpasteurized ones, while those sterilized by high-pressure steam presented undesired and unacceptable browning. Insignificant differences in hardness and chewiness were observed after RF heating. Improvements in mushroom-like flavor occurred after 10 and 20 min of RF heating. CONCLUSION: This study suggests that RF heating for pasteurization of edible mushrooms has promising prospects. Evaluation of RF heating on the taste and nutritional characteristics of edible mushrooms is needed in future work. (c) 2018 Society of Chemical Industry. PMID- 29797730 TI - Non-pharmacological interventions for adults with intellectual disabilities and depression: a systematic review. AB - BACKGROUND: Although high rates of depression symptoms are reported in adults with intellectual disabilities (IDs), there is a lack of knowledge about non pharmacological treatment options for depression in this population. The first research question of this paper is: Which non-pharmacological interventions have been studied in adults with ID and depression? The second research question is: What were the results of these non-pharmacological interventions? METHOD: Systematic review of the literature with an electronic search in six databases has been completed with hand searches. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines have been followed. Selected studies met predefined inclusion criteria. RESULTS: Literature search resulted in 4267 papers of which 15 met the inclusion criteria. Five different types of non pharmacological interventions have been studied: cognitive behavioural therapy, behavioural therapy, exercise intervention, social problem-solving skills programme and bright light therapy. CONCLUSION: There are only a few studies of good quality evaluating non-pharmacological interventions for adults with ID and depression. Some of these studies, especially studies on cognitive behavioural therapy, show good results in decreasing depressive symptoms. High-quality randomised controlled trials evaluating non-pharmacological interventions with follow-up are needed. PMID- 29797729 TI - Ultrafast Photoinduced Multimode Antiferromagnetic Spin Dynamics in Exchange Coupled Fe/RFeO3 (R = Er or Dy) Heterostructures. AB - Antiferromagnetic spin dynamics is important for both fundamental and applied antiferromagnetic spintronic devices; however, it is rarely explored by external fields because of the strong exchange interaction in antiferromagnetic materials. Here, the photoinduced excitation of ultrafast antiferromagnetic spin dynamics is achieved by capping antiferromagnetic RFeO3 (R = Er or Dy) with an exchange coupled ferromagnetic Fe film. Compared with antiferromagnetic spin dynamics of bare RFeO3 orthoferrite single crystals, which can be triggered effectively by ultrafast laser heating just below the phase transition temperature, the ultrafast photoinduced multimode antiferromagnetic spin dynamic modes, for exchange-coupled Fe/RFeO3 heterostructures, including quasiferromagnetic resonance, impurity, coherent phonon, and quasiantiferromagnetic modes, are observed in a temperature range of 10-300 K. These experimental results not only offer an effective means to trigger ultrafast antiferromagnetic spin dynamics of rare-earth orthoferrites, but also shed light on the ultrafast manipulation of antiferromagnetic magnetization in Fe/RFeO3 heterostructures. PMID- 29797731 TI - Desogestrel and panic attacks - a new suspected adverse drug reaction reported by patients and health care professionals on spontaneous reports. PMID- 29797732 TI - Eruptive poromatosis in a patient with breast cancer. AB - Poromas are a group of benign growths of poroid differentiation derived from cells of the terminal sweat duct and connected to the epidermis, normally presenting as solitary papules, plaques or nodules. Rarely they can be eruptive in nature and as such are described as poromatosis. We report an unusual case of widespread poromatosis occurring in a woman with metastatic breast cancer who had recently completed chemo-radiotherapy. PMID- 29797733 TI - Treatment of psoriasis with ustekinumab in a patient with HIV-related Kaposi sarcoma. PMID- 29797735 TI - Absence of immunoglobulin heavy chain rearrangement in primary Merkel cell carcinomas. PMID- 29797734 TI - The first case of congenital blood chimerism in two of the triplets in Korea. AB - BACKGROUND: Chimeras are composed of two or more different populations that originated from different zygotes. Blood chimerism arising from twins have been reported in the literature. Herein, we report the first blood group chimerism in triplets. METHODS: ABO blood grouping was carried out by manual tile methods (Merck Millipore, UK) and micro-column agglutination method (Bio-Rad, Cressier sur Morat, Switzerland). Flow cytometric analysis was performed with Anti-A-PE conjugated monoclonal antibodies (BD Biosciences, San Jose, CA, USA) and FACS Canto II (BD Biosciences). Molecular analysis was performed with allele-specific polymerase chain reaction (AS-PCR) and direct sequencing of the exons 6 and 7. RESULTS: Mixed-field agglutination and weak agglutination against anti-A were revealed by ABO blood grouping. Flow cytometric analysis revealed the presence of both A cells and O cells. AS-PCR and sequencing showed two neonates with chimerism, with each neonate's genotype being A102/O01/O02. CONCLUSION: This is the first recorded case of blood chimera from a triplet in Korea. We recommend full investigation of blood group chimerism in neonates with ABO discrepancy, as blood chimerism is subject to certain caution in the clinical environment. PMID- 29797736 TI - A novel insertion mutation of CDSN responsible for hypotrichosis simplex of scalp in a Chinese family. PMID- 29797737 TI - Outcome of extremely preterm infants after iatrogenic or spontaneous birth. AB - INTRODUCTION: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. MATERIAL AND METHODS: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. RESULTS: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15 3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. CONCLUSIONS: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome. PMID- 29797738 TI - Protein-Assisted Formation and Stabilization of Catalytically Active Polyoxometalate Species. AB - The effect of the protein environment on the formation and stabilization of an elusive catalytically active polyoxometalate (POM) species, K6 [Hf(alpha2 -P2 W17 O61 )] (1), is reported. In the co-crystal of hen egg-white lysozyme (HEWL) with 1, the catalytically active monomeric species is observed, originating from the dimeric 1:2 POM form, while it is intrinsically unstable under physiological pH conditions. The protein-assisted dissociation of the dimeric POM was rationalized by means of DFT calculations. The dissociation process is unfavorable in bulk water, but becomes favorable in the protein-POM complex due to the low dielectric response at the protein surface. The crystal structure shows that the monomeric form is stabilized by electrostatic and water-mediated hydrogen bonding interactions with the protein. It interacts at three distinct sites, close to the aspartate-containing hydrolysis sites, demonstrating high selectivity towards peptide bonds containing this residue. PMID- 29797739 TI - A retrospective study on titanium sensitivity: Patch test materials and manifestations. AB - BACKGROUND: Titanium is being increasingly used. Although it is considered to be a non-allergenic material, allergic reactions to it have been reported. Titanium dioxide has been found to be an unreliable patch test material. Few studies to date have profiled titanium allergy, and it therefore remains difficult to distinguish its manifestations. OBJECTIVES: To evaluate alternatives for titanium dioxide as a patch test preparation, and to profile titanium reactions and manifestations. METHODS: A retrospective chart review was conducted with 458 patients who underwent patch testing with at least 1 of 5 different titanium salts. RESULTS: At least 1 positive result was noted in 5.7% of the patients. The frequency of positive results for the tested salts ranged from 0.9% to 7.9%. Titanium(IV) oxalate hydrate had the highest yield and titanium dioxide the lowest. Erythema, dermatitis and local swelling were the most common objective complaints. In 16 (61.5%) patients, the test result had partial or full clinical relevance. CONCLUSIONS: No titanium-specific risk factors and clinical picture could be identified. Titanium dioxide is not adequately sensitive for identifying titanium allergy. The titanium salts seem to be possible superior patch test preparations, but appear to be unsuitable if used singly. The patient's medical history and clinical picture remain crucial in the diagnostic work-up. PMID- 29797741 TI - Non-pharmacological interventions for neonatal abstinence syndrome. PMID- 29797740 TI - Description of the CARE4STROKE programme: A caregiver-mediated exercises intervention with e-health support for stroke patients. PMID- 29797742 TI - Differences in set-shifting and central coherence across anorexia nervosa subtypes in children and adolescents. AB - OBJECTIVE: Regarding executive functioning in anorexia nervosa (AN), little is known about differences between the restricting (AN-R) and binge eating/purging (AN-BP) subtypes. Especially for adolescents, there is sparse data. Hence, the current aim is to investigate differences in set-shifting, central coherence, and self-reported executive functioning across adolescent AN subtypes. METHODS: Ninety AN-R, 21 AN-BP, and 63 controls completed an extensive assessment battery including neuropsychological tests for executive functioning and the self-report questionnaire Behavior Rating Inventory of Executive Functioning. RESULTS: Patients with AN-R and AN-BP did not differ on neuropsychological measures, and both performed similarly to controls. Behavior Rating Inventory of Executive Functioning scores fell within the normal range with AN subtypes showing mostly comparable ratings. AN-BP patients scored higher on 2 composite indices and the "shift" subscale compared with AN-R. CONCLUSIONS: The results suggest similar cognitive functioning in adolescent AN subtypes as well as healthy controls. However, more research is needed to draw more general conclusions. PMID- 29797743 TI - Demographic, psychiatric, and personality correlates of adults seeking treatment for disordered gambling with a comorbid binge/purge type eating disorder. AB - Preliminary evidence suggests that binge/purge type eating disorders and gambling disorder may commonly co-occur. However, this dual-diagnosis population remains understudied. The present research examined the prevalence rates and correlates of binge/purge type eating disorders (i.e., bulimia nervosa, binge-eating disorder, and anorexia nervosa binge/purge type) among adults seeking treatment for their gambling (N = 349). In total, 11.5% of the sample (n = 40) met criteria for a binge/purge type eating disorder, most commonly bulimia nervosa (n = 33). There was a higher preponderance of binge/purge type eating disorders in women. People with a comorbid binge/purge type eating disorder reported more days gambling, gambling-related cognitive distortions, impulsivity, suicidality, and other current psychiatric comorbidities including addictive behaviours. These findings suggest that binge/purge type eating disorders in people seeking treatment for gambling may be more common than previously believed. Furthermore, the increased psychopathology among people with binge/purge type eating disorder and gambling disorder identify vulnerabilities of this dual-diagnosed population that may require clinical attention. PMID- 29797746 TI - Brief coping strategy enhancement for distressing voices: Predictors of engagement and outcome in routine clinical practice. AB - Cognitive behaviour therapy is recommended internationally as a treatment for psychosis (targeting symptoms such as auditory hallucinations, or "voices"). Yet mental health services are commonly unable to offer such resource-intensive psychological interventions. Brief, symptom-specific and less resource-intensive therapies are being developed as one initiative to increase access. However, as access increases, so might the risk of offering therapy to clients who are not optimally disposed to engage with and benefit from therapy. Thus, it is important to identify who is most/least likely to engage with and benefit from therapy, and when. In the current study, 225 clients were assessed for suitability for a brief, 4-session, manualized, cognitive behaviour therapy-based intervention for voices (named coping strategy enhancement therapy) and 144 commenced therapy, at a transdiagnostic voices clinic based in Sussex, UK. This article reports on the value of depression, anxiety, stress, insight into the origin of voices, length of voice hearing, and demographics in the prediction of engagement and outcomes. The study found that higher levels of baseline depression, anxiety, and stress were significantly associated with poorer outcomes, especially if clients also had high levels of voice-related distress. The engagement analyses showed that levels of voice-related distress at baseline predicted dropout. These findings highlight the importance of assessing negative affect and voice-related distress prior to commencing therapy for distressing voices, to help determine if the client is suitable or ready for brief-coping strategy enhancement. PMID- 29797744 TI - Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease. AB - Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation. PMID- 29797745 TI - Worth a thousand words? Visual concept mapping of the quality of life of people with severe mental health problems. AB - OBJECTIVES: Conventional approaches to quality of life (QoL) measurement rely heavily on verbal, language-based communication. They require respondents to have significant cognitive and verbal ability, making them potentially unsuitable for people with severe mental health problems. To facilitate an alternative approach to QoL assessment, the current study aims to develop an alternative, visual representation of QoL for people with severe mental health problems. METHODS: An alternative, visual adaptation of the concept mapping method was used to construct this visual representation of QoL. Eighty-two participants (i.e., patients, care professionals, and family members) contributed to this study. Results were processed statistically to construct the concept map. RESULTS: The concept map contains 160 unique visual statements, grouped into 8 clusters labelled (1) Support and Attention, (2) Social Contacts, (3) Happiness and Love, (4) Relaxation and Harmony, (5) Leisure, (6) Lifestyle, (7) Finances, and (8) Health and Living. Examples of visual statements are pictures of family silhouettes, romantic couples, natural scenes, houses, sports activities, wallets and coins, smiley faces, and heart shapes. The clusters were interpreted and labelled by participants. CONCLUSIONS: Almost all of the statements correspond to clusters found in previous (non-visual) QoL research. Hence, QoL domains can also be presented visually. PMID- 29797747 TI - Gating by induced Alpha-Gamma asynchrony in selective attention. AB - Visual selective attention operates through top-down mechanisms of signal enhancement and suppression, mediated by alpha-band oscillations. The effects of such top-down signals on local processing in primary visual cortex (V1) remain poorly understood. In this work, we characterize the interplay between large scale interactions and local activity changes in V1 that orchestrates selective attention, using Granger-causality and phase-amplitude coupling (PAC) analysis of EEG source signals. The task required participants to either attend to or ignore oriented gratings. Results from time-varying, directed connectivity analysis revealed frequency-specific effects of attentional selection: bottom-up gamma band influences from visual areas increased rapidly in response to attended stimuli while distributed top-down alpha-band influences originated from parietal cortex in response to ignored stimuli. Importantly, the results revealed a critical interplay between top-down parietal signals and alpha-gamma PAC in visual areas. Parietal alpha-band influences disrupted the alpha-gamma coupling in visual cortex, which in turn reduced the amount of gamma-band outflow from visual areas. Our results are a first demonstration of how directed interactions affect cross-frequency coupling in downstream areas depending on task demands. These findings suggest that parietal cortex realizes selective attention by disrupting cross-frequency coupling at target regions, which prevents them from propagating task-irrelevant information. PMID- 29797748 TI - When your patient's parent asks: "My child's alopecia areata is not getting better. Should he or she get tested for celiac disease?" AB - The relationship between alopecia areata and celiac disease has been suspected for more than 20 years. For a particular individual with alopecia areata, the risk of coexisting celiac disease and the potential benefit of a gluten-free diet on hair loss or regrowth is known. Despite this limited information, patients often aske dermatologists whether they should undergo celiac disease testing or begin a gluten-free diet. We reviewed all available studies of the relationship between alopecia areata and celiac disease to provide guidance to practicing clinicians. PMID- 29797749 TI - Social complexity and kinship in animal societies. AB - Studies of eusocial invertebrates regard complex societies as those where there is a clear division of labour and extensive cooperation between breeders and helpers. In contrast, studies of social mammals identify complex societies as those where differentiated social relationships influence access to resources and reproductive opportunities. We show here that, while traits associated with social complexity of the first kind occur in social mammals that live in groups composed of close relatives, traits associated with the complexity of social relationships occur where average kinship between female group members is low. These differences in the form of social complexity appear to be associated with variation in brain size and probably reflect contrasts in the extent of conflicts of interest between group members. Our results emphasise the limitations of any unitary concept of social complexity and show that variation in average kinship between group members has far-reaching consequences for animal societies. PMID- 29797750 TI - Peptide Nucleic Acid Conjugated with Ruthenium-Complex Stabilizing Double-Duplex Invasion Complex Even under Physiological Conditions. AB - Peptide nucleic acid (PNA) can form a stable duplex with DNA, and, accordingly, directly recognize double-stranded DNA through the formation of a double-duplex invasion complex, wherein a pair of complementary PNA strands form two PNA/DNA duplexes. Because invasion does not require prior denaturation of DNA, PNA holds great potential for in cellulo or in vivo applications. To broaden the applicability of PNA invasion, we developed a new conjugate of PNA with a ruthenium complex. This Ru-PNA conjugate exhibits higher DNA-binding affinity, which results in enhanced invasion efficiency, even under physiological conditions. PMID- 29797751 TI - Histopathologic features of an autopsied patient with cerebral small vessel disease and a heterozygous HTRA1 mutation. AB - Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary cerebral small vessel disease (CSVD) caused by homozygous or compound heterozygous mutations of the high temperature requirement A serine peptidase 1 gene (HTRA1). Affected patients suffer from cognitive impairment, recurrent strokes, lumbago and alopecia. Recently, clinical studies have indicated that some patients with heterozygous mutations in HTRA1 may also suffer CSVD. Here, we report the histopathologic features of an autopsied 55-year-old male patient who had shown cognitive impairment and multiple cerebral infarcts, and was found to have a heterozygous missense mutation (p.R302Q) in the HTRA1 gene. Histologically, small vessels in the brain and spinal cord showed intimal proliferation, splitting of the internal elastic lamina, and degeneration of smooth muscle cells in the tunica media. Thus, although less severe, the features were quite similar to those of patients with CARASIL, indicating that patients with heterozygous mutations develop CSVD through underlying pathomechanisms similar to those of CARASIL. PMID- 29797752 TI - Lymphocytic esophagitis: an update on histologic diagnosis, endoscopic findings, and natural history. AB - Lymphocytic esophagitis is a histologic pattern of injury characterized by increased intraepithelial lymphocytes (>20/high-power field) with rare, or absent granulocytes. Lymphocytes tend to be more numerous in the peripapillary epithelium, and are often associated with evidence of mucosal injury, edema, and scattered dyskeratotic cells. More than a decade following its original description, lymphocytic esophagitis remains an enigmatic entity with variable clinical presentations, associated disorders, etiologies, treatment, and natural history. Most of the confusion regarding the clinical significance of this disorder stems from its diagnostic criteria: lymphocytic esophagitis is currently defined based entirely on histologic criteria, despite the common occurrence of lymphocytosis in a variety of unrelated inflammatory conditions of the esophagus. The goal of this review is to summarize the literature regarding lymphocytic esophagitis and focus on key clinicopathologic features that distinguish it from other esophageal disorders that can show increased numbers of intraepithelial lymphocytes. PMID- 29797753 TI - The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. AB - Sleep reactivity is the trait-like degree to which stress exposure disrupts sleep, resulting in difficulty falling and staying asleep. Individuals with highly reactive sleep systems experience drastic deterioration of sleep when stressed, whereas those with low sleep reactivity proceed largely unperturbed during stress. Research shows that genetics, familial history of insomnia, female gender and environmental stress influence how the sleep system responds to stress. Further work has identified neurobiological underpinnings for sleep reactivity involving disrupted cortical networks and dysregulation in the autonomic nervous system and hypothalamic-pituitary-adrenal axis. Sleep reactivity is most pathologically and clinically pertinent when in excess, such that high sleep reactivity predicts risk for future insomnia disorder, with early evidence suggesting high sleep reactivity corresponds to severe insomnia phenotypes (sleep onset insomnia and short sleep insomnia). High sleep reactivity is also linked to risk of shift-work disorder, depression and anxiety. Importantly, stress-related worry and rumination may exploit sensitive sleep systems, thereby augmenting the pathogenicity of sleep reactivity. With the development of cost-effective assessment of sleep reactivity, we can now identify individuals at risk of future insomnia, shift-work disorder and mental illness, thus identifying a target population for preventive intervention. Given that insomniacs with high sleep reactivity tend to present with severe insomnia phenotypes, patient sleep reactivity may inform triaging to different levels of treatment. Future research on sleep reactivity is needed to clarify its neurobiology, characterize its long-term prospective associations with insomnia and shift-work disorder phenotypes, and establish its prognostic value for mental illness and other non-sleep disorders. PMID- 29797755 TI - Total Syntheses of Crinipellins Enabled by Cobalt-Mediated and Palladium Catalyzed Intramolecular Pauson-Khand Reactions. AB - Efficient total syntheses of the naturally occurring, potent antibiotic compounds (-)-crinipellin A and (-)-crinipellin B are described. The key advanced intermediate, a fully functionalized tetraquinane core, was constructed by a novel thiourea/palladium-catalyzed Pauson-Khand reaction. This intermediate can serve as a common intermediate for the collective total synthesis of other members of the crinipellin family. PMID- 29797754 TI - Change in weight and central obesity by positive airway pressure treatment in obstructive sleep apnea patients: longitudinal data from the ESADA cohort. AB - The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n = 1,415, 77% male, age 54 +/- 11 [mean +/- SD] years, body mass index 31.7 +/- 6.4 kg/m2 , apnea-hypopnea index 37 +/- 24 n per hr, Epworth Sleepiness Scale 10.2 +/- 5.0) were selected. Changes in body mass index and neck/waist/hip circumferences at baseline and at follow-up visit were analysed. Overall, body mass index (0.0 [95% confidence interval, -0.1 to 0.2] kg/m2 ) and neck circumference (0.0 (95% confidence interval, -0.1 to 0.1] cm) were unchanged after positive airway pressure treatment compared with baseline (follow-up duration 1.1 +/- 1.0 years and compliance 5.2 +/- 2.1 hr per day). However, in non-obese (body mass index <30 kg/m2 ) patients, positive airway pressure treatment was associated with an increased body mass index and waist circumference (0.4 [0.3-0.5] kg/m2 and 0.8 [0.4-1.2] cm, respectively, all p < 0.05), and weight gain was significantly associated with higher positive airway pressure compliance and longer positive airway pressure treatment duration. In the obese subgroup, body mass index was reduced after positive airway pressure treatment (-0.3 [-0.5 to -0.1] kg/m2 , p < 0.05) mainly in patients with a strong reduction in Epworth Sleepiness Scale. In conclusion, positive airway pressure therapy was not found to systematically change body mass index in the European Sleep Apnea Database cohort, but the response was heterogeneous. Our findings suggest that weight gain may be restricted to an obstructive sleep apnea phenotype without established obesity. Lifestyle intervention needs to be considered in both lean and obese patients with obstructive sleep apnea receiving positive airway pressure treatment. PMID- 29797756 TI - Tandem Silver Cluster Isomerism and Mixed Linkers to Modulate the Photoluminescence of Cluster-Assembled Materials. AB - Silver chalcogenolate cluster assembled materials (SCAMs) are a category of promising light-emitting materials the luminescence of which can be modulated by variation of their building blocks (cluster nodes and organic linkers). The transformation of a singly emissive [Ag12 (SBut )8 (CF3 COO)4 (bpy)4 ]n (Ag12 bpy, bpy=4,4'-bipyridine) into a dual-emissive [(Ag12 (SBut )6 (CF3 COO)6 (bpy)3 )]n (Ag12 bpy-2) via cluster-node isomerization, the critical importance of which was highlighted in dictating the photoluminescence properties of SCAMs. Moreover, the newly obtained Ag12 bpy-2 served to construct visual thermochromic Ag12 bpy 2/NH2 by a mixed-linker synthesis, together with dichromatic core-shell Ag12 bpy 2@Ag12 bpy-NH2 -2 via solvent-assisted linker exchange. This work provides insight into the significance of metal arrangement on physical properties of nanoclusters. PMID- 29797757 TI - Fecal pollution: new trends and challenges in microbial source tracking using next-generation sequencing. AB - In this minireview, we expand upon traditional microbial source tracking (MST) methods by discussing two recently developed, next-generation-sequencing (NGS) based MST approaches to identify sources of fecal pollution in recreational waters. One method defines operational taxonomic units (OTUs) that are specific to a fecal source, e.g., humans and animals or shared among multiple fecal sources to determine the magnitude and likely source association of fecal pollution. The other method uses SourceTracker, a program using a Bayesian algorithm, to determine which OTUs have contributed to an environmental community based on the composition of microbial communities in multiple fecal sources. Contemporary NGS-based MST tools offer a promising avenue to rapidly characterize fecal source contributions for water monitoring and remediation efforts at a broader and more efficient scale than previous molecular MST methods. However, both NGS methods require optimized sequence processing methodologies (e.g. quality filtering and clustering algorithms) and are influenced by primer selection for amplicon sequencing. Therefore, care must be taken when extrapolating data or combining datasets. Furthermore, traditional limitations of library-dependent MST methods, including differential decay of source material in environmental waters and spatiotemporal variation in source communities, remain to be fully understood. Nevertheless, increasing use of these methods, as well as expanding fecal taxon libraries representative of source communities, will help improve the accuracy of these methods and provide promising tools for future MST investigations. PMID- 29797758 TI - A Simple Strategy to Construct Amorphous Metal-Free Room Temperature Phosphorescent and Multi-Color Materials. AB - It is urgent to develop a universal strategy for producing small organic molecules exhibiting efficient room temperature phosphorescence (RTP). An important contribution made by Ma and Tian et al. provides a general and applicable strategy to obtain amorphous organic molecules with efficient RTP emission by simply modifying phosphors onto beta-cyclodextrin (beta-CD). The nonradiative decay processes and oxygen quenching have been significantly suppressed by the strong intermolecular hydrogen bonding between beta-CD derivatives. Furthermore, the cavity of beta-CDs endows them with the ability to incorporate the adamantane moiety of the fluorescent guest molecules to construct a supramolecular system which exhibits excellent RTP-fluorescence dual emission properties and multicolor emission by altering the host to guest ratio and the excitation wavelength. PMID- 29797760 TI - Transcending data gaps: a framework to reduce inferential errors in ecological analyses. AB - The analysis of functional diversity (FD) has gained increasing importance due to its generality and utility in ecology. In particular, patterns in the spatial distribution and temporal change of FD are being used to predict locations and functional groups that are immediately vulnerable to global changes. A major impediment to the accurate measurement of FD is the pervasiveness of missing data in trait datasets. While such prevalent data gaps can engender misleading inferences in FD analyses, we currently lack any practical guide to handle missing data in trait datasets. Here, we identify significant mismatches between true FD and values derived from datasets that contain missing data. We demonstrate that imputing missing data with a phylogeny-informed approach reduces the risk of misinterpretation of FD patterns, and provides baseline information against which central questions in ecology can be evaluated. PMID- 29797759 TI - Biomimetic Donor-Acceptor Motifs in Conjugated Polymers for Promoting Exciton Splitting and Charge Separation. AB - Natural photosynthesis serves as a model for energy and chemical conversions, and motivates the search of artificial systems that mimic nature's energy- and electron-transfer chains. However, bioinspired systems often suffer from the partial or even large loss of the charge separation state, and show moderate activity owing to the fundamentally different features of the multiple compounds. Herein, a selenium and cyanamide-functionalized heptazine-based melon (DA-HM) is designed as a unique bioinspired donor-acceptor (D-A) light harvester. The combination of the photosystem and electron shuttle in a single species, with both n- and p-type conductivities, and extended spectral absorption, endows DA-HM with a high efficiency in the transfer and separation of photoexcited charge carriers, resulting in photochemical activity. This work presents a unique conjugated polymeric system that shows great potential for solar-to-chemical conversion by artificial photosynthesis. PMID- 29797761 TI - The correlation between intensive care unit attending physician continuity of care with financial and clinical outcomes. AB - PURPOSE: "Attending rotations" on intensive care unit (ICU) services have been in place in most teaching hospitals for decades. However, the ideal frequency of patient care handoffs is unknown. Frequent attending physician handoffs could result in delays in care and other complications, while too few handoffs can lead to provider burnout and exhaustion. Therefore, we sought to determine the correlation between frequency of attending shifts with ICU charges, 30-day readmission rates, and mortality rates. METHODS: We performed a retrospective cohort study at a large, urban, academic community hospital in Baltimore, MD. We included patients admitted into the cardiac or medical ICUs between September 1, 2012, and December 10, 2015. We tracked the number of attending shifts for each patient and correlated shifts with financial outcomes as a primary measure. RESULTS: For any given ICU length of stay, we found no distinct association between handoff frequency and charges, 30-day readmission rates, or mortality rates. CONCLUSIONS: Despite frequent handoffs in care, there was no objective evidence of care compromise or differences in cost. Further validation of these observations in a larger cohort is justified. PMID- 29797764 TI - Direct Participation of a Peripheral Side Chain of a Corrin Ring in Coenzyme B12 Catalysis. AB - The crystal structures of the B12 -dependent isomerases (eliminating) diol dehydratase and ethanolamine ammonia-lyase complexed with adenosylcobalamin were solved with and without substrates. The structures revealed that the peripheral a acetamide side chain of the corrin ring directly interacts with the adenosyl group to maintain the group in the catalytic position, and that this side chain swings between the original and catalytic positions in a synchronized manner with the radical shuttling between the coenzyme and substrate/product. Mutations involving key residues that cooperatively participate in the positioning of the adenosyl group, directly or indirectly through the interaction with the a-side chain, decreased the turnover rate and increased the relative rate of irreversible inactivation caused by undesirable side reactions. These findings guide the engineering of enzymes for improved catalysis and producing useful chemicals by utilizing the high reactivity of radical species. PMID- 29797763 TI - A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers. AB - Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m-2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12). PMID- 29797762 TI - A combined tissue-engineered/in silico signature tool patient stratification in lung cancer. AB - Patient-tailored therapy based on tumor drivers is promising for lung cancer treatment. For this, we combined in vitro tissue models with in silico analyses. Using individual cell lines with specific mutations, we demonstrate a generic and rapid stratification pipeline for targeted tumor therapy. We improve in vitro models of tissue conditions by a biological matrix-based three-dimensional (3D) tissue culture that allows in vitro drug testing: It correctly shows a strong drug response upon gefitinib (Gef) treatment in a cell line harboring an EGFR activating mutation (HCC827), but no clear drug response upon treatment with the HSP90 inhibitor 17AAG in two cell lines with KRAS mutations (H441, A549). In contrast, 2D testing implies wrongly KRAS as a biomarker for HSP90 inhibitor treatment, although this fails in clinical studies. Signaling analysis by phospho arrays showed similar effects of EGFR inhibition by Gef in HCC827 cells, under both 2D and 3D conditions. Western blot analysis confirmed that for 3D conditions, HSP90 inhibitor treatment implies different p53 regulation and decreased MET inhibition in HCC827 and H441 cells. Using in vitro data (western, phospho-kinase array, proliferation, and apoptosis), we generated cell line specific in silico topologies and condition-specific (2D, 3D) simulations of signaling correctly mirroring in vitro treatment responses. Networks predict drug targets considering key interactions and individual cell line mutations using the Human Protein Reference Database and the COSMIC database. A signature of potential biomarkers and matching drugs improve stratification and treatment in KRAS-mutated tumors. In silico screening and dynamic simulation of drug actions resulted in individual therapeutic suggestions, that is, targeting HIF1A in H441 and LKB1 in A549 cells. In conclusion, our in vitro tumor tissue model combined with an in silico tool improves drug effect prediction and patient stratification. Our tool is used in our comprehensive cancer center and is made now publicly available for targeted therapy decisions. PMID- 29797765 TI - Torsion of low-grade appendiceal mucinous neoplasm. PMID- 29797766 TI - Olfactory co-receptor Orco stimulated by Rice stripe virus is essential for host seeking behavior in small brown planthopper. AB - BACKGROUND: Laodelphax striatellus, the small brown planthopper (SBPH), is an economically important pest, besides sucking damage, which transmits rice viruses to cause severe damages to rice. In the process of virus transmission, the host orientation behavior of insect is mainly driven by olfaction. In this context, the molecular basis of olfaction in SBPH is of particular interest. RESULTS: Here, we identified the gene that encodes olfactory receptor co-receptor (Orco) and analyzed its expression profiles in Rice stripe virus (RSV)-infected and RSV free SBPH. It was found that LstrOrco shared high identity with other Orcos from different order insects. LstrOrco was mainly expressed in the head of SBPH, and its expression was significantly stimulated by RSV-infection. The behavioral bioassay revealed that viruliferous SBPH might have a stronger olfactory and seeking ability for rice than RSV-free insect. After silencing of LstrOrco expression, the olfaction and seeking behavior of nymphs for rice seedlings was significantly inhibited, mainly in the increase of the 'no response' percent and the prolongation of the response time. CONCLUSION: These results suggested that Orco played an important role in olfactory signaling and seeking behavior of SBPH, which provided a basic for future development of olfactory-based agriculture pest management strategies. (c) 2018 Society of Chemical Industry. PMID- 29797767 TI - Hypoglycaemia in hospitalized patients with or without heart failure. AB - Hospitalized patients with heart failure (HF) undergoing bedside glucose monitoring with subcutaneous insulin orders were retrospectively identified over 2 years. Hypoglycaemia was defined as any glucose value <3.9 mmol/L (70 mg/dL) within 24 hours of admission (Hypo1day ) or throughout the hospitalization (HypoT ) or any glucose value <2.2 mmol/L (40 mg/dL) throughout the hospitalization (HypoSevere ). A total of 13 424 patients were included, of whom 2484 had HF. Patients with HF were more likely to have Hypo1day (9.1% vs 7.0%, P = .0003), HypoT (28% vs 18.5%, P < .0001), or Hypo Severe (3.4% vs 2.1%, P = .0001). After controlling for other variables, the odds of Hypo1day were similar between the HF and non-HF groups (odds ratio [OR] 1.14, 95% CI 0.94-1.39, P = .18, fully adjusted model), slightly lower for HypoT (OR 0.85, 95% CI 0.73-0.99, P = .03, fully adjusted model), and similar for HypoSevere (OR 1.25, 95% CI 0.91-1.70, P = .17). Hypo1day , HypoT and HypoSevere were all associated with increased mortality; there was no evidence of an interaction by HF status. Hypoglycaemia occurred at a similar or lower frequency in hospitalized patients with HF compared to those without HF. Hypoglycaemia was associated with increased hospital mortality, regardless of HF status. PMID- 29797768 TI - Survival times in dogs with presumptive intracranial gliomas treated with oral lomustine: A comparative retrospective study (2008-2017). AB - Intracranial gliomas are a common malignancy in dogs, and are associated with a poor prognosis due to their aggressive nature and a lack of clinically effective treatments. The efficacies of various treatment modalities for canine brain tumours have been previously described, though little data exist on the use of cytotoxic chemotherapy. A comparative retrospective study, including 40 cases from 5 northeastern US veterinary hospitals, from 2008 to 2017, was conducted. Variables analysed in this study with relation to overall survival and prognostic significance included: age, sex, clinical signs, clinical sign duration, tumour location and treatment protocol used. Dogs with presumptive intracranial gliomas treated with lomustine chemotherapy lived longer (median, 138 days) than those treated exclusively with symptomatic care (median, 35 days; P = .0026 log-rank, 0.0138 Wilcoxon). Additionally, a duration of clinical signs >=16 days prior to diagnosis (median, 109 days) was associated with a longer survival than a duration <16 days prior (median, 25 days; P = .0100 log-rank, 0.0322 Wilcoxon). Lomustine-associated side effects included neutropenia in 46% of dogs, anaemia in 15% and thrombocytopenia in 15%. Potential renal and hepatotoxicity based on increased BUN and/or creatinine and ALT values were reported in 15% and 50% of dogs, respectively. This study provides evidence that lomustine therapy may be effective in prolonging survival in dogs with intracranial gliomas and should be considered as a potential treatment option. Although lomustine-related toxicities are fairly common, they are rarely life threatening and often do not result in discontinuation of therapy. PMID- 29797769 TI - The genome of an endosymbiotic methanogen is very similar to those of its free living relatives. AB - The methanogenic endosymbionts of anaerobic protists represent the only known intracellular archaea, yet, almost nothing is known about genome structure and content in these lineages. Here, an almost complete genome of an intracellular Methanobacterium species was assembled from a metagenome derived from its host ciliate, a Heterometopus species. Phylogenomic analysis showed that the endosymbiont was closely related to free-living Methanobacterium isolates, and when compared with the genomes of free-living Methanobacterium, the endosymbiont did not show significant reduction in genome size or GC content. Additionally, the Methanobacterium endosymbiont genome shared the majority of its genes with its closest relative, though it did also contain unique genes possibly involved in interactions with the host via membrane-associated proteins, the removal of toxic by-products from host metabolism and the production of small signalling molecules. Though anaerobic ciliates have been shown to transmit their endosymbionts to daughter cells during division, the results presented here could suggest that the endosymbiotic Methanobacterium did not experience significant genetic isolation or drift and/or that this lineage was only recently acquired. Altogether, comparative genomic analysis identified genes potentially involved in the establishment and maintenance of the symbiosis, as well provided insight into the genomic consequences for an intracellular archaeum. PMID- 29797770 TI - Transient receptor potential (TRP) channels: a metabolic TR(i)P to obesity prevention and therapy. AB - Cellular transport of ions, especially by ion channels, regulates physiological function. The transient receptor potential (TRP) channels, with 30 identified so far, are cation channels with high calcium permeability. These ion channels are present in metabolically active tissues including adipose tissue, liver, gastrointestinal tract, brain (hypothalamus), pancreas and skeletal muscle, which suggests a potential role in metabolic disorders including obesity. TRP channels have potentially important roles in adipogenesis, obesity development and its prevention and therapy because of their physiological properties including calcium permeability, thermosensation and taste perception, involvement in cell metabolic signalling and hormone release. This wide range of actions means that organ-specific actions are unlikely, thus increasing the possibility of adverse effects. Delineation of responses to TRP channels has been limited by the poor selectivity of available agonists and antagonists. Food constituents that can modulate TRP channels are of interest in controlling metabolic status. TRP vanilloid 1 channels modulated by capsaicin have been the most studied, suggesting that this may be the first target for effective pharmacological modulation in obesity. This review shows that most of the TRP channels are potential targets to reduce metabolic disorders through a range of mechanisms. PMID- 29797771 TI - Review article: Best practice management of closed hand and wrist injuries in the emergency department (part 5 of the musculoskeletal injuries rapid review series). AB - Acute hand and wrist injuries are a common presentation to the ED and are associated with large individual and societal costs. Appropriate management of these injuries in the ED is crucial given that optimal hand function is essential for daily activities and quality of life. This rapid review investigated best practice for the assessment and management of common closed hand and wrist injuries in the ED. Databases were searched in 2017, including PubMed, CINAHL, EMBASE, TRIP and the grey literature, including relevant organisational websites. Primary studies, systematic reviews and guidelines published in English language in the past 12 years that addressed the acute assessment, management, follow-up plan or prognosis were considered for inclusion. Data extraction of included articles was conducted, followed by quality appraisal to rate the level of evidence. The search revealed 2454 articles, of which 55 were included in the review (n = 23 primary articles, n = 26 systematic reviews and n = 6 guidelines). This rapid review provides clinicians who manage common closed fractures and soft tissue injuries of the hand and wrist in the ED, a summary of the best available evidence to enhance the quality of care for optimal patient outcomes. There is evidence to support taking a thorough history and physical examination with consideration of occupational and functional factors, restoring alignment and immobilising when necessary and referring onwards. Key points regarding the diagnosis and management of these injuries are provided. PMID- 29797772 TI - Identification of volatile markers for the detection of adulterants in red ginseng (Panax ginseng) juice using headspace stir-bar sorptive extraction coupled with gas chromatography and mass spectrometry. AB - Red ginseng (Panax ginseng) products are frequently adulterated by manufacturers with cheaper medicinal plant products including deodeok (Codonopsis lanceolata) and doraji (Platycodon grandiflorum) to increase profits. To identify possible volatile markers for the adulteration of red ginseng juices with deodeok or doraji, a headspace stir-bar sorptive extraction method was developed. Gas chromatography with mass spectrometry and untargeted metabolomics analysis revealed that 1-hexanol, cis-3-hexen-1-ol, and trans-2-hexen-1-ol are abundantly present in deodeok and doraji but not red ginseng. The peak area ratios in gas chromatograms of these compounds in red ginseng juices mixed with deodeok or doraji indicate that these volatile chemicals can be used as markers to detect the adulteration of red ginseng juice. PMID- 29797773 TI - Baseline Characteristics of the Autosomal Dominant Polycystic Kidney Disease Subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). AB - AIM: The aim of this study was to describe the baseline characteristics of autosomal dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). METHODS: From April 2011 to February 2016, patients with CKD stage 1 to 5 (pre-dialysis) were enrolled as an ADPKD subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function, and the factors associated with kidney function were analyzed. RESULTS: A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 +/- 33.3 mL/min/1.73 m2 (50.5% male with a mean age of 47.0 +/- 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6% and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 than the other age groups. Older age, a higher 24-hour urine protein excretion, larger htTKV, and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR. CONCLUSION: This subcohort will provide clinical characteristics and outcomes of Korean ADPKD patients and can compare with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD. This article is protected by copyright. All rights reserved. PMID- 29797774 TI - Clustered miRNAs and their role in biological functions and diseases. AB - MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions. PMID- 29797775 TI - Practice patterns of female urologists in Australia and New Zealand. AB - OBJECTIVE: To analyse the practice patterns of female urologists in Australia and New Zealand. PARTICIPANTS AND METHODS: An electronic survey was sent to female urologists and urology trainees of the Urological Society of Australia and New Zealand in December 2016, with questions on demographics, practice patterns and views on mentorship. RESULTS: Of 82 recipients of the questionnaire, 60 (73.2%) responded. Of these, 61.7% were aged <40 years, 81.7% were married or in a long term relationship and 56.7% had children. A total of 67.8% had completed urology training. Of these, most had commenced clinical practice within the preceding 12 years, most had taken no time off in training and most had taken <1 year away from clinical practice. A total of 74.4% practised in a metropolitan area and 42.5% described their practice as being general urology. High or moderate satisfaction levels were reported by 88.1% of respondents and 92.9% intended to retire before the age of 70 years. A total of 17.2% had not had a mentor and 80.7% thought a mentorship scheme would be useful. CONCLUSION: These results provide information on the practice patterns of the increasing number of women urologists in Australia and New Zealand and have the potential to shape workforce and training planning in this region and worldwide. PMID- 29797776 TI - Continuous In-Line Virus Inactivation for Next Generation Bioprocessing. AB - Viral inactivation plays a critical role in assuring the safety of monoclonal antibody (mAb) therapeutics. Traditional viral inactivation involves large holding tanks in which product is maintained at a target low pH for a defined hold time, typically 30-60 min. The drive toward continuous processing and improved facility utilization has provided motivation for development of a continuous viral inactivation process. To this end, a lab-scale prototype viral inactivation system was designed, built, and characterized. Multiple incubation chamber designs are evaluated to identify the optimal design that enables narrow residence time distributions in continuous flow systems. Extensive analysis is conducted supporting rapid low pH viral inactivation and included evaluations with multiple viruses, a range of pH levels, buffer compositions, mAb concentrations, and temperatures. Multiple test conditions are evaluated using the in-line system and results compared to traditional batch-mode viral inactivation. Comparability in kinetics of virus inactivation suggests equivalency between the two approaches. PMID- 29797777 TI - Missing data handling in non-inferiority and equivalence trials: A systematic review. AB - BACKGROUND: Non-inferiority (NI) and equivalence clinical trials test whether a new treatment is therapeutically no worse than, or equivalent to, an existing standard of care. Missing data in clinical trials have been shown to reduce statistical power and potentially bias estimates of effect size; however, in NI and equivalence trials, they present additional issues. For instance, they may decrease sensitivity to differences between treatment groups and bias toward the alternative hypothesis of NI (or equivalence). AIMS: Our primary aim was to review the extent of and methods for handling missing data (model-based methods, single imputation, multiple imputation, complete case), the analysis sets used (Intention-To-Treat, Per-Protocol, or both), and whether sensitivity analyses were used to explore departures from assumptions about the missing data. METHODS: We conducted a systematic review of NI and equivalence trials published between May 2015 and April 2016 by searching the PubMed database. Articles were reviewed primarily by 2 reviewers, with 6 articles reviewed by both reviewers to establish consensus. RESULTS: Of 109 selected articles, 93% reported some missing data in the primary outcome. Among those, 50% reported complete case analysis, and 28% reported single imputation approaches for handling missing data. Only 32% reported conducting analyses of both intention-to-treat and per-protocol populations. Only 11% conducted any sensitivity analyses to test assumptions with respect to missing data. CONCLUSION: Missing data are common in NI and equivalence trials, and they are often handled by methods which may bias estimates and lead to incorrect conclusions. PMID- 29797778 TI - Progression to total hip arthroplasty following hip arthroscopy. AB - BACKGROUND: Hip arthroscopy is a minimally invasive surgical technique increasingly being used to treat hip pathology. There is evidence that a proportion of patients require total hip arthroplasty in the years immediately following arthroscopy, suggesting that these patients have derived only a limited benefit from the procedure. Identification of risk factors for early progression to hip arthroplasty may enable refinement of hip arthroscopy indications and more informed decision making. The aim of this study is to identify the proportion of patients in a hip arthroscopy cohort who progress to total hip arthroplasty within 2 years of arthroscopy, and to analyse risk factors for this early progression. METHODS: A retrospective cohort analysis was conducted on all patients who underwent hip arthroscopy at one tertiary institution from 2004 to 2013. Hospital data were linked to the Australian Orthopaedic Association National Joint Replacement Registry in 2016 to identify subsequent hip arthroplasty. RESULTS: There were 989 arthroscopies performed on 947 patients; 447 were female (48.1%), the mean age was 41.1 years (SD: 14.23) and osteoarthritis was present at arthroscopy in 31.5%. Total hip arthroplasty occurred in 129 patients (13%) within 2 years. Multivariable logistic regression revealed osteoarthritis, age >50 years and previous arthroscopy were significant risk factors for arthroplasty within 2 years (adjusted odds ratios (confidence intervals): 4.6 (2.91-7.16), 3.8 (2.44-5.87), 2.5 (1.16-5.81)). CONCLUSIONS: Osteoarthritis, older age and history of arthroscopy were independent risk factors for early progression to arthroplasty; these factors should be considered within clinical decision-making, and when discussing potential arthroscopy outcomes with patients. PMID- 29797779 TI - The interplay among stress, frustration tolerance, mindfulness, and social support in Internet gaming disorder symptoms among Chinese working adults. AB - INTRODUCTION: Internet gaming disorder (IGD) is a growing mental health threat across age groups, but existing literature regarding IGD mainly focuses on student populations. Empirical investigation of the risk and protective factors in adult populations is warranted. This study aimed to fill the research gap by examining whether stress and 3 positive psychology factors (ie, frustration tolerance, mindfulness, and social support) are associated with IGD symptoms in working adults. It was also the first attempt to test the buffering effects of these positive psychology factors on the relationship between stress and IGD vulnerability. METHOD: This cross-sectional study was conducted in Shenzhen, China. We recruited 327 full-time working Chinese adults (mean age = 31.93 years), who had online gaming experience and voluntarily completed an anonymous questionnaire with DSM-5 criteria to measure their IGD symptoms. RESULTS: Internet gaming disorder symptoms were positively correlated with stress and negatively correlated with the 3 positive psychology factors, among which mindfulness emerged as the most salient protective factor. Moreover, mindfulness, but not frustration tolerance and social support, was found to significantly alleviate the relationship between stress and IGD. DISCUSSION: Our findings provide supportive evidence for the protective and moderating roles of positive psychology variables against IGD among Chinese working adults. Workplace-based prevention programs may take the identified factors into account to help promote individuals' personal resources to mitigate development of IGD. PMID- 29797781 TI - The impact of growth rate and environmental factors on mutation rates and spectra in Escherichia coli. AB - Genetic variation in bacterial populations is remarkably sensitive to environmental influences, including simple, nutritional differences. Not only the rate but also the kind of mutational changes is biased by the nutritional state of bacteria. Here we investigate the mutational consequences of a universal variable for free-living bacteria, namely the growth rate. By controlling growth in chemostats, the rate and mix of mutations was investigated for populations of Escherichia coli subject to different specific growth rates. Both aerobic and anaerobic cultures were compared with see if growth rate is a factor in the commonest respiratory conditions for E. coli. We find mutation rates are raised markedly with decreasing growth rate. Base pair substitutions and 1-bp insertions and deletions increase with reduced growth rate, but less so in anaerobic cultures. Insertion sequence movements are particularly sensitive to growth rate, with IS2 being optimal at intermediate growth rates whereas IS1 and IS150 movements are highest at the slowest tested growth rate. A comprehensive comparison of growth rate effects, as well as six other environmental factors, provides the most complete picture yet of the range of mutational signatures in bacterial genetic variation. PMID- 29797780 TI - Autoimmune antibodies and asbestos exposure: Evidence from Wittenoom, Western Australia. AB - BACKGROUND: Studies comparing different forms of asbestos are rare, and limited by the failure to compare results with unexposed populations. We compare autoimmune responses among former workers and residents of the crocidolite mining and milling town of Wittenoom, Western Australia, with an unexposed population. METHODS: ANA testing using indirect immunofluorescence was performed on randomly selected serum samples from Wittenoom workers or residents and compared with those from participants of another unexposed cohort study. RESULTS: ANA scores were higher in the Wittenoom participants compared with Busselton and the odds of being ANA positive was fivefold greater among Wittenoom participants than Busselton (OR 5.5, 95%CI 2.3-13.0). CONCLUSIONS: This study is the first to report increased ANA positivity among persons exposed exclusively to crocidolite. This finding of a high frequency of positive ANA tests among crocidolite-exposed subjects may be an indicator for an increased risk of systemic autoimmune diseases and needs further scrutiny. PMID- 29797782 TI - What is the role of the isolated small water pool near FeMo-co, the active site of nitrogenase? AB - The enzyme nitrogenase converts N2 to NH3 , and hydrogenates many other small unsaturated molecules, using multiple electrons and multiple protons. The protein contains a number of water structures in the vicinity of the active site, FeMo co, and functional roles have been assigned to two of these with detailed mechanisms proposed for the serial ingress of protons and the egress of product NH3 . A separate small water pool (SWP), in a different part of the protein surrounding FeMo-co, has unknown function. A recent investigation of protein crystals soaked in low-pH buffer revealed changes in residues near this SWP, and suggested that it could be involved in proton transfer steps. This paper examines the SWP in three protein crystal structures, Azotobacter vinelandii (Av1) and Clostridium pasterianum (Cp1) in their neutral resting states, and Cp1 at low pH. The H atoms, not observed crystallographically, were patched in through density functional calculations using large protein models. Optimisation of the various possibilities, with assessment against crystal dimensions, yielded the most probable distributions of hydrogen atoms in the hydrogen bonds, and the location of H3 O+ in the low-pH state. These detailed structures vary in water content and water involvement with surrounding residues, and vary also in their hydrogen bonding to S atoms of FeMo-co. A conserved mechanism for proton transfer to FeMo co is not evident, and it is concluded that the SWP has no role in the mechanism of nitrogenase. PMID- 29797783 TI - Kidney symptom questionnaire: Development, content validation and relationship with quality of life. AB - BACKGROUND: Chronic kidney disease (CKD) is associated with a range of symptoms, even at early stages. The importance of patient symptom experience is increasingly recognised, but validated symptom scores are lacking. OBJECTIVES: This study aimed to refine an existing symptom questionnaire for use with patients not requiring renal replacement therapy (RRT), carry out content validity testing and explore convergent validity by comparing symptom scores with quality of life (QoL). DESIGN: A mixed-methods approach involving questionnaires, semi-structured interviews and a focus group. PARTICIPANTS: Patients with CKD not undergoing RRT and expert health professionals. APPROACH: Two hundred and nineteen patients completed an existing symptom questionnaire. The most commonly reported symptoms were identified, and descriptions refined in 11 semi-structured interviews. The questionnaire design was reviewed by a focus group. Content validity was established by a panel of expert health professionals. Seventy patients completed both the symptom questionnaire and a health-related QoL questionnaire (EQ-5D-5L). RESULTS: Thirteen common symptoms were identified. During the content validity phase, 13/16 experts responded (81%); 10/13 symptoms had 'excellent' or 'good' evaluation scores, and the content validity index of the whole questionnaire was 0.81, falling within the recommended threshold. Total symptom frequency scores, number of symptoms and the frequencies of 10/13 individual symptoms were all strongly associated with health-related QoL (EQ-5D 5L index score; p < 0.002 for all). CONCLUSION: This work has provided a new, validated symptom score for patients with CKD not requiring RRT for clinical management and research purposes. PMID- 29797784 TI - Susceptibility to antibiotics in isolates of Lactobacillus plantarum RAPD-type Lp299v, harvested from antibiotic treated, critically ill patients after administration of probiotics. AB - Recultured Lactobacillus plantarum 299v-like strains were tested regarding antibiotic susceptibility, and no decrease was detected. Antibiotics are frequently used to treat patients in intensive care units (ICUs) and are associated with a significant risk of selection of resistant bacterial strains. In particular, it is possible that genetic transfer of antibiotic resistance to the resident gastrointestinal flora, as well as to administered probiotics, may be increased in the ICU setting. The aim of the present investigation was to detect possible changes in antimicrobial susceptibility in reisolates of the probiotic strain Lactobacillus plantarum 299v (Lp299v) given to antibiotic treated, critically ill patients. Lp299v-like strains were identified in cultures of biopsies and fecal samples from 32 patients given the probiotic strain enterally in two previous ICU studies. The patients received a variety of antibiotics. Isolates with the same genomic RAPD profile (RAPD-type) as Lp299v were obtained to enable monitoring of antibiotic susceptibility by E-tests. Forty two isolates, collected throughout the course of illness, were tested against 22 different antibiotics. No obvious decrease in susceptibility was found for 21 of the tested antibiotics. There was a tendency toward decreased susceptibility to ampicillin. The stable antibiotic susceptibility profiles of the Lp299v-like isolates studied here suggests this probiotic is less likely to acquire resistance when administered to critically ill patients treated with broad spectrum antibiotics. PMID- 29797785 TI - Computational investigation on the binding modes of Rimonabant analogs with CB1 and CB2. AB - The human cannabinoid G-protein-coupled receptor 1 (CB1) is highly expressed in central nervous system. CB1-selective antagonists show therapeutic promise in a wide range of disorders, such as obesity-related metabolic disorders, dyslipidemia, drug abuse, and type 2 diabetes. Rimonabant (SR141716A), MJ08, and MJ15 are selective CB1 antagonists with selectivity >1,000-folds over CB2 despite 42% sequence identity between CB1 and CB2. The integration of homology modeling, automated molecular docking, and molecular dynamics simulation were used to investigate the binding modes of these selective inverse agonists/antagonists with CB1 and CB2 and their selectivity. Our analyses showed that the hydrophobic interactions between ligands and hydrophobic pockets of CB1 account for the main binding affinity. In addition, instead of interacting with ligands directly as previously reported, the Lys1923.28 in CB1 was engaged in indirect interactions with ligands to keep inactive-state CB1 stable by forming the salt bridge with Asp1762.63 . Lastly, our analyses indicated that the selectivity of these antagonists came from the difference in geometry shapes of binding pockets of CB1 and CB2. The present study could guide future experimental works on these receptors and has the guiding significance for the design of functionally selective drugs targeting CB1 or CB2 receptors. PMID- 29797786 TI - Generation of High Expressing Chinese Hamster Ovary Cell Pools Using the Leap-In Transposon System. AB - Clonally derived cell lines (CDCL) from Chinese Hamster Ovary (CHO) host cell lines, remain the most popular method to manufacture therapeutic proteins. However, CHO cell pools are increasingly being used as an alternate method to produce therapeutic proteins for preclinical drug development in an effort to shorten the time required for new drug development. It is essential that these CHO pools exhibit the desired attributes of CHO CDCLs such as high protein titers and consistent product quality attributes (PQAs). In this study the authors evaluated the Leap-In Transposase(r), for the expression of four different proteins (three mAbs and one Bispecific mAb). The resultant pool titers ranges from 2.0 to 5.0 g L-1 for the four proteins compared to 1.5-3.3 g L-1 from the respective control pools (generated by random gene integration). The resultant cell pools are a homogeneously expressing cell population. The average gene copy numbers are similar or lower in the evaluation pools relative to the control pools. The higher titers in the evaluation pools are attributed to higher levels of both IgG-LC and IgG-HC mRNA. In conclusion, the Leap-In transposase generates high titer, homogeneous CHO pools in a short time-period without introducing any undesired PQAs. PMID- 29797787 TI - Caring for older patients in the emergency department: Health professionals' perspectives from Australia - The Safe Elderly Emergency Discharge project. AB - OBJECTIVE: To explore health professionals' perspectives about caring for community-dwelling older patients in the ED. METHODS: This exploratory qualitative study was undertaken with emergency nursing, medical and allied health staff from the ED of a large metropolitan public hospital in Melbourne. Nine focus groups (n = 54) and seven interviews were conducted between 2013 and 2014. Data were thematically analysed. RESULTS: Health professionals described tailoring their approach when caring for older patients, including adopting a specific communication approach (i.e. increased voice volume, slower rate of speech). Caring for older patients was perceived as challenging given the need to balance the expectations of family members to deal with associated complex needs and limited time for transitional care planning in the ED. The environment and equipment were perceived as unsuitable, alongside a lack of geriatric-specific knowledge; contributing to what health professionals described as a poor fit between the ED system and older patients' needs. CONCLUSION: The growing number of older patients presents numerous challenges for emergency health professionals and necessitates a tailored approach to care. Understanding health professionals' perspectives about caring for older patients can inform strategies that may improve the quality of care. Creating older person-friendly areas, improving transitional care and providing staff with specific education would foster an environment that promotes person-centred care, safety, independence and functional wellbeing. PMID- 29797788 TI - Using digital inpainting to estimate incident light intensity for the calculation of red blood cell oxygen saturation from microscopy images. AB - Red blood cell oxygen saturation (SO2 ) is an important indicator of oxygen supply to tissues in the body. SO2 can be measured by taking advantage of spectroscopic properties of hemoglobin. When this technique is applied to transmission microscopy, the calculation of saturation requires determination of incident light intensity at each pixel occupied by the red blood cell; this value is often approximated from a sequence of images as the maximum intensity over time. This method often fails when the red blood cells are moving too slowly, or if hematocrit is too large since there is not a large enough gap between the cells to accurately calculate the incident intensity value. A new method of approximating incident light intensity is proposed using digital inpainting. This novel approach estimates incident light intensity with an average percent error of approximately 3%, which exceeds the accuracy of the maximum intensity-based method in most cases. The error in incident light intensity corresponds to a maximum error of approximately 2% saturation. Therefore, though this new method is computationally more demanding than the traditional technique, it can be used in cases where the maximum intensity-based method fails (eg, stationary cells), or when higher accuracy is required. PMID- 29797789 TI - Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe hemorrhage. PMID- 29797790 TI - Thermoelectric heat exchange and growth regulation in a continuous yeast culture. AB - We have designed a thermoelectric heat exchanger (TEHE) for microbial fermentations that is able to produce electric power from a microbial continuous culture using the intrinsic heat generated by microbial growth. While the TEHE was connected, the system proved able to stably self-maintain both the temperature and the optical density of the culture. This paves the way toward a more sustainable operation of microbial fermentations, in which energy could be saved by converting part of the metabolic heat into usable electric power. PMID- 29797791 TI - Early activation of CD95 is limited and localized to the cytotoxic synapse. AB - The cytotoxic synapse formed between cytotoxic T lymphocytes or natural killer cells expressing CD95L and target cells with CD95 on their surface is a key pathway for apoptosis induction by the immune system. Despite similarities with the immune synapse in antigen presenting cells, little is known about the role of the spatiotemporal organization of agonistic proteins/receptor interactions for CD95 signaling. Here, we have developed an artificial cytotoxic synapse to examine how mobility and geometry of an anti-CD95 agonistic antibody affect receptor aggregation and mobility, ie the first step of receptor activation. By measuring the distribution, diffusion coefficient, and fraction of immobile CD95 receptor in living cells, we show that at short times, the initial activation of CD95 occurs locally and is limited to the contact region of the cytotoxic synapse. This anisotropic activation of apoptotic signaling supports a role for confined interactions on the efficiency of signal transduction that may have implications for biomedical applications of extrinsic apoptosis induction. PMID- 29797792 TI - The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology. AB - The therapeutic challenge of advanced, recurrent, and refractory cervical cancer (CC) needs to develop new molecularly targeted drugs. Rad21 is an important regulatory gene that maintains the correct dissociation of sister chromatids during cell mitosis. The aim of this study was to investigate the effect of Rad21 on CC. Rad21 expression in CC and cervical intraepithelial neoplasia III was significantly increased. Women with the rs2289937 C genotype (CC+CT) of rs4570 and rs4579555 genotypes and haplotype 1 (TTTCAGGCGC) were significantly associated with CC risk, while women with low frequencies of haplotype 6 (TTTTAGGCGC) also increased the risk of CC.Rad21-specific shRNA decreased cancerous cell proliferation, migration, and invasion and increased the proportion of cells in G2/M phase as well as sensitivity to radiation. The Rad21 influenced the expression of XPO1, CyclinB1, CDK1, P21, P27, and P53 through up and downregulating the Rad21 expression. The TCGA database of CC also showed that Rad21 expression was associated with poor disease survival and XPO1 expression. Moreover, the KEGG pathway indicated that Rad21 is broadly involved in the cell cycle and RNA transportation via XPO1. This suggests that Rad21 involves the development of cervical cancer possibly by participating in the regulation of cell cycle and the nuclear output of the tumor suppressor gene via XPO1. PMID- 29797794 TI - Identification and characterization of bladder cancer by low-resolution fiber optic Raman spectroscopy. AB - Raman spectroscopy has been proved to be a promising diagnostic technique for various cancers detection. A major drawback for its clinical translation is the intrinsic weakness of Raman effects. Highly sensitive equipment and optimal measurement conditions are generally applied to overcome this drawback. However, these equipment are usually bulky, expensive and may also be easily influenced by surrounding environment. In this preliminary work, a low-resolution fiber-optic Raman sensing system is applied to evaluate the diagnostic potential of Raman spectroscopy to identify different bladder pathologies ex vivo. A total number of 262 spectra taken from 32 bladder specimens are included in this study. These spectra are categorized into 3 groups by histopathological analysis, namely normal bladder tissues, low-grade bladder tumors and high-grade bladder tumors. Principal component analysis fed artificial neural network are used to train a classification model for the spectral data with 10-fold cross-validation and an overall prediction accuracy of 93.1% is obtained. The sensitivities and specificities for normal bladder tissues, low-grade bladder tumors and high-grade bladder tumors are 88.5% and 95.1%, 90.3% and 98%, and 97.5% and 96.4%, respectively. These results demonstrate the potential of using a low-resolution fiber-optic Raman system for in vivo bladder cancer diagnosis. PMID- 29797793 TI - Next-generation sequencing unravels extensive genetic alteration in recurrent ovarian cancer and unique genetic changes in drug-resistant recurrent ovarian cancer. AB - BACKGROUND: By using a high-throughput sequencing technique, we sought to delineate genetic alterations in recurrent ovarian cancer patients and further compare genetic changes in drug-resistant and -sensitive recurrent ovarian cancer patients. We also sought to study the specificity, sensitivity, and consistency of DNA biomarkers in liquid biopsy specimens and ovarian cancer tissue DNA. METHODS: Tumor tissue specimens and blood samples were obtained from pathologically proven recurrent ovarian cancer patients. Genomic DNA was extracted from tumor tissues, blood cells, ascites, and urine samples. The DNA Library was constructed and sequencing was performed using the Illumina HiSeq 4000 high-throughput sequencing platform. Bioinformatic analysis was done using the Torrent Suite software. RESULTS: Ten patients with pathologically proven drug resistant recurrent ovarian cancer and 11 patients with sensitive recurrent ovarian cancer were included. The 5-year OS for drug-resistant recurrent ovarian cancer patients (44 +/- 11.07 months, 95% CI: 231.24-53.66 months) was significantly lower than that of drug-sensitive recurrent ovarian cancer patients (58 +/- 3.97 months; 95% CI: 50.05-65.59 months; p = 0.024) TP53 was the most frequently mutated gene in both drug-resistant (9/10, 90%) and drug-sensitive recurrent ovarian cancers (10/11, 91%). MYC and RB1 had the highest frequency of copy number variations (6/21, 29%) in recurrent ovarian cancers, followed by PIK3CA (3/21, 14%). BRCA2 N372H polymorphism was found in 40% (4/10) of drug resistant recurrent ovarian cancer patients. The specificity, sensitivity, and consistency of TP53 and BRCA1 in circulating tumor-free DNA and tumor tissue DNA were 100%, 73.7%, 76.2% and 100%, 75%, 95.24%, respectively. CONCLUSION: We uncovered extensive genetic alterations in recurrent ovarian cancer and drug resistant recurrent ovarian cancer exhibited unique genetic changes compared with recurrent ovarian cancer and drug-sensitive recurrent ovarian cancer. We further showed that high-throughput sequencing using liquid biopsy specimens could provide an effective, specific, and sensitive approach for detecting genetic alterations in ovarian cancer. PMID- 29797795 TI - Vapor toxicity of five volatile pyrethroids against Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles quadrimaculatus (Diptera: Culicidae). AB - BACKGROUND: Mosquito mortality has been documented in numerous studies of spatial repellents but the concentration-dependent toxicity of spatial repellent vapors has not been documented. To address this issue, prallethrin, flumethrin, metofluthrin, transfluthrin, and meperfluthrin were selected for comparative study against Aedes albopictus (Skuse), Ae. aegypti (L.), Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. Mosquito were exposed to vapors of each chemical for 2, 4, and 24 h with mortality recorded at each time point. A second experiment involved exposing mosquitoes to vapors for 2 h, then transferring them to untreated holding containers and held for 24 h. For these mosquitoes, readings were only taken after 24 h to allow for metabolic detoxification and recovery. RESULTS: LC50 and LC90 data indicated that transfluthrin and meperfluthrin had the greatest toxicity across all species, followed by metofluthrin, prallethrin, and flumethrin. CONCLUSION: Our findings, through the direct comparison of these compounds, suggest that transfluthrin, meperfluthrin, and metofluthrin be considered for further development. The vapor toxicity for the aforementioned compounds significantly exceeds prallethrin, which is currently market available as an adulticidal active ingredient in public health pest control. (c) 2018 Society of Chemical Industry. PMID- 29797796 TI - Assignment of cytomegalovirus infection status in infants awaiting solid organ transplant: Viral detection methods as adjuncts to serology. AB - Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18 months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status. The proportion of CMV-seropositive infants decreased from 52% in infants 0-6 months of age to 28% in those 12-18 months. Among CMV-seropositive infants, median OD was significantly higher in the 6- to 12- and 12- to 18-month groups compared to the 0- to 6-month group. Distribution of OD by age group suggested that maternal antibody cleared before 12 months. Of 59 eligible CMV-seropositive infants, 49 (83%) had CMV viral detection studies and 18 of 49 (36.7%) had detectable CMV: 9 of 30 (30.0%) infants 0-6 months, 7 of 15 (46.7%) infants 6-12 months, and 2 of 4 (50.0%) infants 12-18 months. CMV viral detection studies are useful to confirm positive CMV infection status in CMV-seropositive infants awaiting SOT. Maternal CMV IgG likely clears before 12 months. PMID- 29797798 TI - Developmental Trajectories of Chinese Adolescents' Relational Aggression: Associations With Changes in Social-Psychological Adjustment. AB - This study investigated the development of relational aggression (RA) in a sample of Chinese youth (N = 2,274, 52% boys) from fourth (Mage = 10.27 years) to ninth grade. Using latent class growth analysis, four trajectories were identified for both peer- and teacher-rated RA: a no aggression trajectory, a low-increasing trajectory, a moderate-decreasing trajectory, and a chronically high trajectory. Chronically high RA showed a chronicity effect on adolescent peer acceptance, rejection, and rule-breaking behaviors. Adolescents showed worse adjustment as RA increased, but they did not necessarily evidence significant improvement in adjustment even if their RA decreased. Findings reveal the maladaptive nature of RA and highlight the importance of considering cultural context in understanding RA. PMID- 29797797 TI - Impact of maternal pre-pregnancy overweight on infant overweight at 1 year of age: associations and sex-specific differences. AB - BACKGROUND: Maternal overweight or obesity (OWOB) is linked to gestational diabetes, fetal macrosomia and higher rates of caesarean delivery. OBJECTIVES: The study aims to assess whether maternal pre-pregnancy OWOB is associated with infant overweight in a sex-dependent manner, independent of microbiota-altering variables. METHODS: Weight and length measurements of 955 mother-infant pairs were obtained from the Canadian Healthy Infant Longitudinal Development cohort. Maternal pre-pregnancy weight was defined as follows: normal, overweight (25 <= body mass index < 30) and obese (body mass index >= 30). Age and sex-adjusted weight-for-length z-scores >97th percentile were classified as infant overweight at age 1 year. Associations between pre-pregnancy and infant overweight were determined by linear and logistic regression, adjusting for covariates. RESULTS: Maternal pre-pregnancy OWOB were associated with infant weight-for-length and overweight risk at 1 year. Except for pre-pregnancy obesity, these associations were not attenuated appreciably after adjustment for birth mode, exclusivity of breastfeeding, exposure to antibiotics and infant sex. Yet only boys born to mothers with obesity were three times more likely to become overweight at age 1 independent of microbiota-altering variables. Pre-pregnancy obesity was associated with weight-for-length in male and female infants. CONCLUSIONS: Maternal pre-pregnancy OWOB increases the risk of infant overweight, and this association is more evident in male infants. PMID- 29797800 TI - Sleeping Well Trial: Increasing the effectiveness of treatment with continuous positive airway pressure using a weight management program in overweight adults with obstructive sleep apnoea-A stepped wedge randomised trial protocol. AB - BACKGROUND: The majority of adults diagnosed with obstructive sleep apnoea (OSA) are overweight or obese. Continuous positive airway pressure (CPAP) is the most common effective therapy for OSA. However, adherence declines over time with only 50% of patients prescribed CPAP continuing to use it long term. Furthermore, a recent prospective analysis indicated that those more adherent with CPAP therapy have enhanced weight gain trajectories which in turn may negatively impact their OSA. AIM: The Sleeping Well Trial aims to establish whether the timing of starting a lifestyle weight loss intervention impacts on weight trajectory in those with moderate-severe OSA treated at home with CPAP, while testing the potential for smart phone technology to improve adherence with lifestyle interventions. METHODS: A stepped wedge design with randomisation of individuals from 1 to 6 months post-enrolment, with 5 months of additional prospective follow up after completion of the stepped wedge. This design will investigate the effect of the 6-month lifestyle intervention on people undergoing CPAP on body weight, body composition and health-related quality of life. DISCUSSION: This trial tests whether the timing of supporting the patient through a weight loss intervention is important in obtaining the maximum benefit of a lifestyle change and CPAP usage, and identify how best to support patients through this critical period. TRIAL REGISTRATION: The protocol (v1) is registered prospectively with the International Clinical Trials Registry (CTR) ACTRN12616000203459 (public access). Any amendments to protocol will be documented via the CTR. Recruitment commenced in March 2016 with data collection scheduled to finish by May 2018. PMID- 29797799 TI - Fatty infiltration evaluation and selective pattern characterization of lower limbs in limb-girdle muscular dystrophy type 2A by muscle magnetic resonance imaging. AB - INTRODUCTION: Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterized by progressive wasting of muscles for which the disease-monitoring tools are still deficient. METHODS: We performed muscle MRI of the lower limbs in 32 LGMD2A patients and 21 controls. The modified Mercuri scale was employed to evaluate the degree of fatty infiltration. RESULTS: Severe fatty infiltration in the long head of biceps femoris (modified Mercuri scale 3.99) and sparing of extensor digitorum longus (modified Mercuri scale 0.17) were observed. The sensitivity and specificity of this pattern in diagnostic testing was 76.00% and 90.48%, respectively. A comprehensive clinical and MRI evaluation revealed that progressive fatty infiltration in the upper leg correlated well with disease progression, but neither calf involvement nor muscle strength deterioration showed a good correlation. DISCUSSION: The selective involvement pattern is potentially useful for LGMD2A diagnosis. Upper leg muscle MRI is a sensitive evaluation method for monitoring disease progression. Muscle Nerve 58: 536-541, 2018. PMID- 29797801 TI - Metal- and Additive-Free Oxidation of Sulfides into Sulfoxides by Fullerene Modified Carbon Nitride with Visible-Light Illumination. AB - Photocatalytic selective oxidation has attracted considerable attention as an environmentally friendly strategy for organic transformations. Some methods have been reported for the photocatalytic oxidation of sulfides into sulfoxides in recent years. However, the practical application of these processes is undermined by several challenges, such as low selectivity, sluggish reaction rates, the requirement of UV-light irradiation, the use of additives, and the instability of the photocatalyst. Herein, a metal-free C60 /graphitic carbon nitride (g-C3 N4 ) composite photocatalyst was fabricated by a facile method, and well characterized by TEM, SEM, FTIR spectroscopy, XRD, X-ray photoelectron spectroscopy, diffuse reflectance spectroscopy, and photoluminescence spectroscopy. The C60 /g-C3 N4 catalyst exhibited a high photocatalytic activity at room temperature for the selective oxidation of sulfides into the corresponding sulfoxides in the presence of other functional groups, due to the synergetic roles of C60 and g-C3 N4 . Several important parameters have been screened, and this method afforded good to excellent yields of sulfoxides under optimal conditions. The superoxide radical (. O2- ) and singlet oxygen (1 O2 ) were identified as the oxidative species for the oxidation of sulfides into sulfoxides by exploring EPR experiments, and hence, a plausible mechanism for this oxidation was proposed. Moreover, the C60 /g-C3 N4 catalyst can be easily recovered by filtration and then reused at least four times without loss in activity. PMID- 29797802 TI - Glucose transporter-1 (GLUT-1) expression in psoriasis: correlation with disease severity. AB - BACKGROUND: Epidermal hyperproliferation with abnormal differentiation, inflammation, and angiogenesis are the key features of psoriasis. Glucose transporter-1 (GLUT-1) is a member of facilitative sugar transporters that are integral membrane glycoproteins moving sugar across cell membrane. OBJECTIVE: The objective of this study was to study the GLUT-1 expression in psoriasis. PATIENTS AND METHODS: Forty patients with psoriasis vulgaris and 20 healthy individuals were included in the study. Skin biopsies were taken from lesional and nonlesional skin of psoriasis patients as well as normal skin of control subjects. All were examined for GLUT-1 antibody expression by immunohistochemistry and GLUT-1 mRNA expression by real-time polymerase chain reaction (RT-PCR). In addition, specimens of psoriasis lesions were stained by hematoxylin and eosin and CD31 for morphometric analysis of histopathological parameters. RESULTS: The intensity of GLUT-1 immunohistochemical expression and the relative levels of GLUT-1 mRNA expression in psoriasis lesions were upregulated in lesional skin of psoriasis patients in comparison with their nonlesional skin as well as normal control skin. GLUT-1 expression in psoriasis lesions showed significant positive correlations with Psoriasis Area and Severity Index (PASI) score, mean of epidermal thickness, inflammatory cell density, and microvessel density. CONCLUSION: Glucose transporter-1 could play a role not only in the onset of psoriasis but also in the progression and severity of the disease. It may participate in the pathogenesis of psoriasis through the facilitation of epidermal hyperproliferation, inflammation, and angiogenesis. PMID- 29797804 TI - Polymer-free versus permanent polymer-coated drug eluting stents for the treatment of coronary artery disease: A meta-analysis of randomized trials. AB - BACKGROUND: Polymer-free drug eluting stents (PF-DES) were developed, in part, to overcome risk of late ischemic events observed with permanent polymer-coated DES (PP-DES). However, trial results are inconsistent with longer-term safety and efficacy of PF-DES remaining unknown. We performed a meta-analysis of randomized trials assessing outcomes of patients receiving PF-DES versus PP-DES for treatment of coronary artery disease (CAD). METHODS: Electronic searches were performed for randomized trials comparing outcomes between PF-DES and PP-DES. Trials reporting major adverse cardiovascular events (MACE), myocardial infarction (MI), stent thrombosis (ST), all-cause death, target lesion/vessel revascularization (TLR/TVR), and late lumen loss (LLL) were included. Analyses were performed at longest follow-up and landmarked beyond 1-year. RESULTS: Twelve trials (6,943 patients) were included. There was no significant difference in MACE between PF-DES and PP-DES at longest follow-up (Odds Ratio [OR] 0.96, 95%CI 0.85-1.10, P = 0.59) or landmark analysis beyond 1-year (OR 0.96, 95%CI 0.76 1.20, P = 0.70). Although PF-DES were associated with a significant reduction in all-cause death (OR 0.85, 95%CI 0.72-1.00, P < 0.05), this effect was not present on landmark analysis beyond 1-year (OR 0.89, 95%CI 0.73-1.10, P = 0.30). There were no differences observed for MI (OR 1.00, 95%CI 0.77-1.28, P = 0.99) or ST (OR 0.95, 95%CI 0.54-1.68, P = 0.86), with similar efficacy outcomes including TVR (OR 1.07, 95%CI 0.91-1.26, P = 0.42), TLR (OR 1.03, 95%CI 0.88-1.21, P = 0.68) and angiographic LLL (pooled mean difference 0.01 mm, 95%CI -0.08 to 0.11, P = 0.76). CONCLUSIONS: PF-DES are as safe and efficacious as PP-DES for the treatment of patients with CAD, but do not significantly reduce late ischemic complications. PMID- 29797805 TI - Linking phytoplankton community metabolism to the individual size distribution. AB - Quantifying variation in ecosystem metabolism is critical to predicting the impacts of environmental change on the carbon cycle. We used a metabolic scaling framework to investigate how body size and temperature influence phytoplankton community metabolism. We tested this framework using phytoplankton sampled from an outdoor mesocosm experiment, where communities had been either experimentally warmed (+ 4 degrees C) for 10 years or left at ambient temperature. Warmed and ambient phytoplankton communities differed substantially in their taxonomic composition and size structure. Despite this, the response of primary production and community respiration to long- and short-term warming could be estimated using a model that accounted for the size- and temperature dependence of individual metabolism, and the community abundance-body size distribution. This work demonstrates that the key metabolic fluxes that determine the carbon balance of planktonic ecosystems can be approximated using metabolic scaling theory, with knowledge of the individual size distribution and environmental temperature. PMID- 29797803 TI - Impact of lung-function measures on cardiovascular disease events in older adults with metabolic syndrome and diabetes. AB - BACKGROUND: Individuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD). HYPOTHESIS: Lung-function measures can predict CVD events in older persons with MetS, DM, and neither condition. METHODS: We followed 4114 participants age >= 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1-second forced expiratory volume (FEV1 ; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years. RESULTS: DM was present in 537 (13.1%) and MetS in 1277 (31.0%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16% (HR: 0.84, 95% CI: 0.59-1.18), 23% (HR: 0.77, 95% CI: 0.60-0.99), and 30% (HR: 0.70, 95% CI: 0.58 0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV1 , CVD risk was lower by 2% (HR: 0.98, 95% CI: 0.70-1.37), 26% (HR: 0.74, 95% CI: 0.59 0.93), and 31% (HR: 0.69, 95% CI: 0.57-0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C-statistics increased significantly with addition of FEV1 or FVC over risk factors for CVD and CHF among those with neither MetS nor DM. CONCLUSIONS: FEV1 and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons. PMID- 29797806 TI - Root surface alterations following manual and mechanical scaling: A comparative study. AB - OBJECTIVES: The aim of this study was to investigate the morphological and surface roughness changes in dental root samples following periodontal scaling by hand curette, piezoelectric ultrasonic devices or a combination of these. METHODS: Twenty-four monoradicular teeth extracted as a result of periodontal disease were divided into 4 groups: Group A was treated by piezoelectric ultrasonic scaler Piezon(r) Master 400; Group P by piezoelectric ultrasonic scaler PiezoSmart(r) ; Group C using Gracey curette 7/8; Group AC by a combined technique of piezoelectric ultrasonic scaler Piezon(r) Master 400 and Gracey curette 7/8. The treated samples were then analysed using a white light interferometer and scanning electron microscopy (SEM). RESULTS: Roughness analysis revealed major surface alterations in Group C (Sa = 24.98 MUm); the samples treated using the combined technique (Group AC) showed reduced but still significant alteration (Sa = 14.48 MUm), while samples treated with the piezoelectric ultrasonic devices (Group A and Group P) presented the lowest roughness values (Sa = 8.99 and Sa = 4.45 MUm, respectively). A significant difference was found between groups C and P (P = 0.036). SEM analysis confirmed the roughness analysis revealing non-homogeneous surfaces in Group C, while a less morphological alteration was noted in the other groups. CONCLUSION: All periodontal devices used in this in vitro study produced a certain degree of surface alteration. Hand curettes appear to have a major impact on surface integrity compared with piezoelectric ultrasonic devices. PMID- 29797807 TI - Neutrophil Gelatinase-Associated Lipocalin as a Promising Novel Biomarker for Early Detection of Kidney Injury. PMID- 29797808 TI - Rejuvenating Aged Hematopoietic Stem Cells Through Improvement of Mitochondrial Function. AB - Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD+ dietary supplements, known as niacin or vitamin B3, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD+ precursor supplementation. PMID- 29797809 TI - Reducing Test Utilization in Hospital Settings: A Narrative Review. AB - BACKGROUND: Studies addressing the appropriateness of laboratory testing have revealed approximately 20% overutilization. We conducted a narrative review to (1) describe current interventions aimed at reducing unnecessary laboratory testing, specifically in hospital settings, and (2) provide estimates of their efficacy in reducing test order volume and improving patient-related clinical outcomes. METHODS: The PubMed, Embase, Scopus, Web of Science, and Canadian Agency for Drugs and Technologies in Health-Health Technology Assessment databases were searched for studies describing the effects of interventions aimed at reducing unnecessary laboratory tests. Data on test order volume and clinical outcomes were extracted by one reviewer, while uncertainties were discussed with two other reviewers. Because of the heterogeneity of interventions and outcomes, no meta-analysis was performed. RESULTS: Eighty-four studies were included. Interventions were categorized into educational, (computerized) provider order entry [(C)POE], audit and feedback, or other interventions. Nearly all studies reported a reduction in test order volume. Only 15 assessed sustainability up to two years. Patient-related clinical outcomes were reported in 45 studies, two of which found negative effects. CONCLUSIONS: Interventions from all categories have the potential to reduce unnecessary laboratory testing, although long-term sustainability is questionable. Owing to the heterogeneity of the interventions studied, it is difficult to conclude which approach was most successful, and for which tests. Most studies had methodological limitations, such as the absence of a control arm. Therefore, well-designed, controlled trials using clearly described interventions and relevant clinical outcomes are needed. PMID- 29797810 TI - Platelet Function Analyzer-200 P2Y Results Are Predictive of the Risk of Major Adverse Cardiac Events in Korean Patients Receiving Clopidogrel Therapy Following Acute Coronary Syndrome. AB - BACKGROUND: Clopidogrel is one of the most commonly used anti-platelet agents in cardiovascular diseases. We analyzed the relationship between the platelet function analyzer (PFA)-200 P2Y (INNOVANCE PFA-200 System, Siemens Healthcare, Germany) results and occurrence of major adverse cardiac events (MACEs) in Korean patients with recent-onset acute coronary syndrome (ACS) taking clopidogrel. METHODS: Between August 2013 and June 2016, we prospectively enrolled 106 patients with recent-onset ACS who had been treated with clopidogrel. We obtained blood samples and measured closure time (CT) using the PFA-200 P2Y test. Patients were divided into two groups on the basis of a CT cut-off value of 106 seconds. We compared patient characteristics and various MACEs that occurred during the follow-up period. RESULTS: The CTs for 78 patients exceeded the cut-off value. At the time of these analyses, 11 patients had been diagnosed with MACEs. In the time-to-event analysis, there was a difference between the two groups (P<0.001). After adjusting other variables associated with MACE occurrence, CT value was the strongest predictor of MACEs, with a 7.30-fold occurrence risk (P=0.002). CONCLUSIONS: We found a strong relationship between CT and MACE risk in Korean patients with recent-onset ACS taking clopidogrel. Accordingly, PFA-200 P2Y results could be used as a predictive marker for MACE risk in such patients. PMID- 29797811 TI - Proposed Imprecision Quality Goals for Urinary Albumin/Creatinine Ratio. AB - BACKGROUND: The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty. METHODS: The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results. RESULTS: The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8-15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively. CONCLUSIONS: We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results. PMID- 29797812 TI - Plasma Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Renal Parenchymal Involvement in Infants With Febrile Urinary Tract Infection: A Preliminary Study. AB - BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in infants. Renal parenchymal involvement is an important prognostic factor; however, early detection of parenchymal involvement in UTI may be difficult during infancy. This study aimed to assess whether a recently established biomarker of UTI, neutrophil gelatinase-associated lipocalin (NGAL), can serve as a useful marker for the detection of cortical defects (CD) and to determine the appropriate diagnostic cut-off value of NGAL in infants with febrile UTI. METHODS: Infants hospitalized for febrile UTI were divided into two groups according to the presence of cortical defects on dimercaptosuccinic acid (DMSA) scintigraphy. Among 64 enrolled infants, 43 (67%) had CD (UTI-CD) and 21 (33%) had no CD (UTI-ND). The white blood cell count, C-reactive protein, and plasma NGAL (pNGAL) levels were determined before antibiotic therapy and compared between the two groups. RESULTS: pNGAL level was significantly higher in the UTI CD group than in the UTI-ND group (340 MUg/L vs 214 MUg/L, P=0.002). Multivariate analysis showed that pNGAL level was the only independent predictor of CD (odds ratio 2.759, P=0.039). In the ROC curve analysis, pNGAL showed the highest area under the curve (0.745; 95% confidence interval, 0.561-0.821; P=0.014). The appropriate cut-off value of pNGAL was 267 MUg/L (sensitivity, 72.1%; specificity, 71.4%). CONCLUSIONS: pNGAL was found to be a useful marker for early prediction of renal parenchymal involvement in infants with febrile UTI. PMID- 29797813 TI - Postprandial Lipid Concentrations and Daytime Biological Variation of Lipids in a Healthy Chinese Population. AB - BACKGROUND: Several latest guidelines and consensus statements from Europe and the United States specify that there is no need for fasting prior to routine lipid tests. However, the latest Chinese guidelines still recommend fasting tests owing to a lack of local evidence. This study aimed to investigate postprandial lipid concentrations and daytime biological variation of lipids in a healthy Chinese population. METHODS: Venous blood samples were collected from 41 ostensibly healthy Chinese volunteers at five time points during the day (06:30, 09:00, 12:00, 15:00, and 18:30). The same batch of reagents was used to determine lipid concentrations. A nested ANOVA was performed to calculate within-subject biological variation (CV(I)) and between-subject biological variation (CV(G)). RESULTS: Postprandial concentrations of triglyceride were higher than fasting concentrations, with the maximum change occurring at 12:00 (0.5 hours after lunch, 0.21+/-0.65 mmol/L difference). The daytime biological variation of triglycerides was relatively high (CV(I)=25%, CV(G)=35.9%). The postprandial concentrations of total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were mostly lower than the fasting concentrations, and their daytime biological variations were relatively low (CV(I)=2.4-4.4%, CV(G)=11.8-18.7%). CONCLUSIONS: As most daytime lipid concentrations changed only slightly, non-fasting samples could be used for routine lipid tests. However, in cases of abnormal postprandial triglyceride concentrations, dietary factors and fasting time should be considered when interpreting the results. PMID- 29797814 TI - Evaluation of the Luminex ARIES HSV 1&2 Assay and Comparison with the FTD Neuro 9 and In-house Real-Time PCR Assays for Detecting Herpes Simplex Viruses. AB - BACKGROUND: Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for a plethora of human diseases, of which cutaneous and mucocutaneous infections are the most prevalent. In its most severe form, HSV infection can cause meningitis/encephalitis. We compared the Luminex ARIES HSV 1&2 assay (Luminex Corp., Austin, TX, USA), an automated sample-to-result molecular solution, to two non-automated HSV DNA assays. METHODS: A total of 116 artificial controls were used to determine the analytical performance of the ARIES assay. Controls were prepared by spiking universal transport medium (UTM) and cerebrospinal fluid (CSF) samples from patients who tested negative for HSV by an in-house HSV-1 and -2 DNA assay with reference materials (SeraCare Life Sciences, MA, USA; ZeptoMetrix Corp., MA, USA). Another 117 clinical samples were then used to compare the clinical performance of the ARIES assay with those of an in-house assay and the FTD Neuro 9 assay (Fast Track Diagnostics, Junglinster, Luxembourg). RESULTS: The analytical sensitivity (95% limit of detection) of the ARIES assay was 318 copies/mL (UTM samples) and 935 copies/mL (CSF samples) for HSV-1 strain 96 and 253 copies/mL (UTM samples) and 821 copies/mL (CSF samples) for HSV-2 strain 09. No cross-reactivity was observed in samples spiked with 14 non-HSV microorganisms. Compared with the reference result (agreement between the in-house and FTD Neuro 9 results), the ARIES assay had overall concordance rates of 98.2% (111/113) and 100% (113/113) for HSV-1 and HSV-2, respectively. CONCLUSIONS: The ARIES assay appears to be an excellent alternative for rapid detection and differentiation of HSV in skin and genital infections, meningitis, and encephalitis. PMID- 29797815 TI - Asymmetrical Dimethylarginine Levels in Hepatitis B Virus-Positive Patients. AB - BACKGROUND: High asymmetrical dimethylarginine (ADMA) levels have been associated with endothelial dysfunction and contribute to the development of several diseases. However, data on the relationship between hepatitis B virus (HBV) and ADMA are limited. The aim of our study was to explore the relationship between ADMA and HBV by comparing the ADMA levels in patients with chronic active hepatitis B (CHB), inactive HBV carriers (carriers), and healthy volunteers (controls). METHODS: The participants were divided into three groups: 90 patients with CHB, 90 HBV carriers, and 90 controls. Serum ADMA levels were quantified using an ELISA kit (Cusabio, Wuhan, China). The data were analyzed using an ANOVA or the Kruskal-Wallis test as appropriate, with P<0.05 considered significant. RESULTS: Serum ADMA levels were significantly higher in patients with CHB (228.35+/-91.10 ng/mL) than in HBV carriers (207.80+/-75.80 ng/mL) and controls (207.61+/-89.10 ng/mL) (P=0.049). The clinical scores of the patients were positively correlated with ADMA levels. CONCLUSIONS: The elevated serum ADMA levels in patients with CHB confirm that HBV plays a role in vasculitis. Further investigation of the mechanisms contributing to the high levels of ADMA in CHB may contribute toward development of new treatment modalities. PMID- 29797817 TI - Diagnostic Performance and Comparative Evaluation of the Architect, Liaison, and Platelia Epstein-Barr Virus Antibody Assays. AB - BACKGROUND: Epstein-Barr Virus (EBV) is one of the most prevalent causes of viral infection in humans. EBV infection stage (acute, past, or absent infection) is typically determined using a combination of assays that detect EBV-specific markers, such as IgG and IgM antibodies against the EBV viral capsid antigen (VCA) and IgG antibodies against the EBV nuclear antigen (EBNA). We compared the diagnostic performance and agreement of results between three commercial EBV antibody assays using an EBV performance panel (SeraCare Life Science, Milford, MA, USA) as a reference. METHODS: EBV antibody tests of EBV VCA IgM, VCA IgG, and EBNA IgG antibodies were performed by the Architect (Abbott Diagnostics, Wiesbaden, Germany), Liaison (DiaSorin, Saluggia, Italy), and Platelia (Bio-Rad, Marnes-la-Coquette, France) assays. Agreement between the three assays was evaluated using 279 clinical samples, and EBV DNA and antibody test results were compared. RESULTS: The three EBV antibody assays showed good diagnostic performance with good and excellent agreement with the performance panel (kappa coefficient, >0.6). The overall VCA IgM positivity rate was higher in EBV DNA positive samples than in EBV DNA-negative samples for all three EBV antibody assays (P=0.02). The three EBV antibody assays exhibited good agreement in results for the clinical samples. CONCLUSIONS: The diagnostic performance of the three EBV antibody assays was acceptable, and they showed comparable agreement in results for the clinical samples. PMID- 29797816 TI - Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients. AB - BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. METHODS: Pre transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. RESULTS: Pre-transplant HLA-DSA, anti AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (-) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017-24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti AT1R. CONCLUSIONS: Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue. PMID- 29797818 TI - The Role of the Signal-to-Cutoff Ratio in Automated Anti-HCV Chemiluminescent Immunoassays by Referring to the Nucleic Acid Amplification Test and the Recombinant Immunoblot Assay. AB - BACKGROUND: Following discontinuation of the recombinant immunoblot assay (RIBA), the only available supplementary test for the detection of hepatitis C virus (HCV) is the nucleic acid amplification test (NAAT). However, the NAAT does not adequately detect past HCV. Consequently, it is hard to distinguish between past HCV infection and biological false positivity with an anti-HCV result alone. We assessed the diagnostic performance of two immunoassays: the ARCHITECT anti-HCV chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, Wiesbaden, Germany) and the Access HCV Ab PLUS chemiluminescent immunoassay (CIA; Bio-Rad, Marnes-la-Coquette, France). We also explored an optimized algorithm to determine the anti-HCV results. METHODS: We tested 126,919 patients and 44,556 individuals who underwent a medical checkup. RIBA and NAAT were conducted for samples that tested anti-HCV-positive using CMIA and CIA. We assessed the optimal signal-to cutoff (S/CO) ratio in HCV-positive samples. RESULTS: In total, 1,035 blood samples tested anti-HCV-positive. Of these, RIBA was positive in 512, indeterminate in 160, and negative in 363 samples. One hundred sixty-five samples were NAAT-positive. Diagnostic sensitivity and positive predictive value (PPV) were 96.7% and 52.1%, respectively, for CMIA, and 94.7% and 72.3%, respectively, for CIA. The optimal S/CO ratio was 5.2 for CMIA and 2.6 for CIA at 95% PPV. In total, 286 samples tested positive in CMIA and 444 in CIA, while 443 samples tested positive in both assays. CONCLUSIONS: It is hard to determine anti-HCV positivity based on the S/CO ratio alone. However, this study elucidated the role of the S/CO ratio by using the NAAT and RIBA. PMID- 29797821 TI - Performance Evaluation of the Preanalytic Module of the ACL TOP 750 Hemostasis Lab System. PMID- 29797822 TI - Performance of Microflex LT Biotyper and VITEK MS for Routine Identification of Yeasts. PMID- 29797823 TI - First Case of Pasteurella multocida Pneumonic Bacteremia in Korea. PMID- 29797820 TI - The 2016 WHO versus 2008 WHO Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia. AB - The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (>=1*109/L and >=10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately. PMID- 29797819 TI - Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability. AB - BACKGROUND: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. METHODS: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. RESULTS: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. CONCLUSIONS: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability. PMID- 29797824 TI - PCM1-JAK2 Fusion in a Patient With Acute Myeloid Leukemia. PMID- 29797826 TI - Bringing the oral healthcare message to life through the innovative 'Extra Tooth Booth'. PMID- 29797825 TI - Plus Disease in Retinopathy of Prematurity: More Than Meets the ICROP? AB - Retinopathy of prematurity (ROP), a vasoproliferative retinal disease affecting premature infants, is a leading cause of childhood blindness throughout the world. Plus disease, defined as venous dilatation and arteriolar tortuosity within the posterior retinal vessels greater than or equal to that of a standard published photograph, is the most critical finding in identifying treatment requiring ROP. Despite an internationally accepted definition of plus disease, there is significant variability in diagnostic process and outcome, producing variable levels of reported intra- and interexpert agreement. Several potential explanations for poor agreement have been proposed, including attention to undefined vascular features such as venous tortuosity, focus on narrower or wider field of view, unfamiliarity with digital images, the magnification and apparent severity of the standard photograph, and cut-off point differences among experts as to the level of tortuosity and dilation sufficient for "plus disease" along a continuum. Moreover, differences in diagnostic consistency among groups of experts separated both geographically and chronologically have been reported. These findings have implications for clinical care, research, and education, and highlight the need for a more precise definition of plus disease and objective diagnostic methods for ROP. PMID- 29797828 TI - Breakage of endodontic instruments: Patients need to know that endodontic instruments can sometimes break. PMID- 29797827 TI - Lifelong learner. PMID- 29797829 TI - How to properly instruct your dental technician/laboratory: Communication is key when working with a dental technician/laboratory. PMID- 29797831 TI - The non-healing extraction socket: a diagnostic dilemma - case report and discussion. AB - STATEMENT OF THE PROBLEM: Delayed healing, or failure of the alveolus to heal post exodontia, is not an uncommon finding in both primary care and hospital practice. Local factors dominate and the majority of cases are the result of clot dissolution, secondary infection, foreign bodies, etc. However, potentially life threatening, malignant lesions complicating healing can be overlooked and underestimated due to their rare occurrence. PURPOSE OF THE REVIEW: This article presents a contemporary review of the normal physiological process that directs healing within the extraction socket and a differential diagnosis for delayed healing or failure of healing following extraction, with guidance on appropriate management. METHOD: A case report of a squamous cell carcinoma presenting in the clinical setting of a non-healing extraction socket, and a discussion of local and systemic factors that may interfere with healing, are presented. CONCLUSION: The aetiologies of delayed healing and failure of the extraction site to heal are diverse, and the process can be affected by local and systemic factors alike.'Given that neoplastic lesions are relatively rare, it is therefore all the more important for GDPs to remain cognisant of the diagnostic red flags that may raise suspicions of a mitotic lesion to ensure that appropriate referral pathways are instituted. PMID- 29797830 TI - Simple technique to evaluate denture border extensions using silicone impression material. AB - INTRODUCTION: Extension of denture borders beyond the border line can lead to abnormal movement of the denture and therefore possible loss of retention. Soreness or sore spots that appear in the day(s) after insertion may also result from the overextended borders. OBJECTIVES: This article presents a simple technique to evaluate denture border extensions using silicone impression material. MATERIALS AND METHODS: One scoop of heavy body silicone is laid on the borders of the denture. The denture is inserted into the mouth and the usual functional movements are performed to investigate any overextensions. - Conclusion: This method is simple, time as well as material saving, and does not need extra instruments or devices. PMID- 29797832 TI - An opportunity exists: The new Government seems to be preparing to support dental treatments for the public. The Association has been preparing for its interaction with the Government on this issue. PMID- 29797834 TI - Communicating with the dental laboratory. PMID- 29797835 TI - Reducing tax liability: A number of tax reliefs are available to help reduce income tax liabilities for individuals, both employees and the self-employed. PMID- 29797833 TI - Emergency injuries. PMID- 29797836 TI - Your retirement planning checklist: There are many things you can do to maximise your pension pot and ensure a comfortable retirement. PMID- 29797837 TI - Focus group methods in dental research. AB - INTRODUCTION: Focus group methods have been increasingly used in dental research. However, although focus group methods appear quite simple and easy to carry out, there are a number of complexities that need to be considered. METHOD: The present integrative review was carried out to assess the usability of focus group methods for dental research. RESULTS: Three key themes were identified from the qualitative review: the complexity of the method; benefits of focus group research for dentistry; and, the nature of the quality controls employed. CONCLUSION: A key strength of using focus groups is that they can enhance qualitative and quantitative methodologies by helping to clarify, extend, qualify, or challenge what has been found. PMID- 29797839 TI - Exchanging views. PMID- 29797840 TI - Letter to the Editor. PMID- 29797838 TI - Multiple myeloma presenting as mandibular pain. AB - INTRODUCTION: Multiple myeloma (MM) is a systemic malignancy of plasma cells defined by monoclonal production of circulating immunoglobulins. Bone pain is a presenting feature in the majority of cases. Treatment may involve intravenous use of bisphosphonates, chemotherapy or haematopoietic stem cell transplantation. Here, we illustrate a first presentation of MM in a patient with mandibular pain and discuss radiographic, diagnostic and treatment challenges of orofacial issues in patients with MM. CASE REPORT: A 69-year-old lady presented to an emergency oral surgery clinic with a month-long history of unilateral left-sided pain in her jaw. Examination revealed a buccolingual swelling of 2cm diameter in the lower left premolar region. Radiographic images demonstrated a 2cm lytic lesion in her mandible corresponding with the symptomatic region. Aspiration of the lesion was performed and histological analysis indicated an abundance of atypical plasma cells. Subsequent biopsy revealed sheets of plasmacytoid cells suggesting evidence of a plasmacytoma. Skeletal survey, bone marrow biopsy and serum analysis confirmed the presence of MM. DISCUSSION: MM, although a systemic malignancy, can present via a variety of orofacial manifestations. The presence of a lytic lesion on plain radiographs should alert the dental practitioner to the possibility of the diagnosis. Treatment of orofacial bone pain may respond to intravenous bisphosphonates but care must be taken to avoid osteonecrosis of the jaw. CONCLUSION: This case is an important reminder of the potential oral presentations of MM and underlines the importance of radiographic evaluation in patients with atypical symptoms and presentations. PMID- 29797841 TI - Postgraduate Diploma in Conscious Sedation in Dentistry. PMID- 29797842 TI - The role of saliva in promoting oral health. PMID- 29797843 TI - Looking forward to phase three. PMID- 29797844 TI - You can't be too careful: Take a full assessment of a patient's medical history or there may be unnecessary complications. PMID- 29797845 TI - Five steps for success in endodontics. PMID- 29797846 TI - A retrospective investigation of the oral health records of a cohort of preschool children who received extractions under general anaesthesia including cost analysis of treatment. AB - : Internationally, a considerable proportion of children aged five years and younger require extraction of teeth due to dental caries and frequently dental general anaesthesia (DGA) is the treatment of choice. AIMS: To investigate the records of a cohort of preschool children (aged five years and younger) referred to the public dental service provided at Cork University Hospital (CUH), Cork, Ireland, for extractions under DGA between the years 2000 and 2002. To determine the characteristics of the sample: disadvantage; the presence of a significant medical history; and, fluoride status. To establish the pattern of appointments and care, before, during and after DGA, and the pattern of dental treatment required up to sixth class (aged 11 to 12 years). METHODS: A retrospective review of dental records of a cohort of preschool-aged children referred for DGA in CUH during the years 2000-2002 was completed. Demographic and clinical data were collated and analysed using Statistical Packages for Social Sciences (SPSS). Costs were provided by CUH and the Health Service Executive (HSE). Data on costs relating to preventive programmes were obtained from information presented in the Irish Oral Health Services Guideline Initiative 2009.1 Results: A total of 347 children were included with a median age of.fQur years and a range of one to five years. Children with a disadvantage were more likely to require extractions under DGA than their- counterparts (50%, n=175). In total, 73% (n=253)~ of patients had a fluoridated water supply and 91% (n=316) had no adverse medical history. For 88% (n=306), their first dental visit was an emergency appointment. The primary indication for DGA was treatment of dental caries. A recall appointment was provided for 18% (n=63). One-quarter (n=86) required an extraction, antibiotic or referral for a second DGA at their first visit following DGA. In first class, referral for a second DGA or extraction under local anaesthetic (LA) was required for 23% (n=79) of patients. Over 60% (n=21 1) required either an extraction or a restoration in third class. In excess of 20% (n=69) of patients did not attend the sixth class dental inspection, the final assessment appointment in the public services. CONCLUSIONS: A considerable number of preschool children require extractions under DGA due to dental caries. The results of this study indicate that such children progress to adolescence with poor oral health, as evidenced by the need for further restorations, extractions and repeat DGA. The average cost of DGA was E819 per child. This figure has been shown to be as much as eight times the cost of a preventive/oral health promotion prograrnme operating within a similar cohort. An integrated preventive programme targeting preschool-aged children should be considered in attempting to manage the hicih levels of dental caries within this age group. PMID- 29797847 TI - A Review on Translucent Zirconia. AB - INTRODUCTION: Zirconia is suggested in many clinical situations due to acceptable biocompatibility, lower price compared with gold restorations, and better appearance than traditional metal ceramic restorations. New translucent monolithic zirconia has been developed to merge strength with improved tooth colour matching. This work aims to review relevant articles on new translucent zirconia restorative materials. METHODS: The published articles on translucent zirconia were searched through PubMed, Medline, Google scholar, and indexed journals using the following keywords: translucent zirconia, transparent zirconia, and tooth colored zirconia. The most relevant articles were selected and reviewed. RESULT: Introduction of translucent zirconia, has brought the advantages such as less tooth preparation, biological compatibility, high strength, good mechanical properties, and less antagonist wear. However, the effects of altering material constituents to increase translucency on properties such as phase transformation and low temperature degradation may warrant further investigations. CONCLUSION: Translucent zirconia can be prescribed in many clinical situations and may provide less complicated procedures compared with the production of multilayer restorations of opaque zirconia cores and translucent feldspathic veneers. This may otherwise decrease fabrication time and defects, improve biological properties, reduce abutment tooth reduction, and result in less antagonist tooth attrition. PMID- 29797848 TI - Prosthetic Rehabilitation with Implant-Supported Mandibular Overdenture after Partial Glossectomy and Radiation Therapy: A Case Report. AB - Implant-supported overdenture is a well-established treatment option for many patients who have functional problems with conventional dentures. It may be primary choice for patients with altered jaw anatomy, neuromuscular disorders, pronounced gag reflex, severe residual ridge resorption and oral tissue defects. In this article we describe a case report, where tongue cancer patients occlusion was rehabilitated with an implantretained overdenture. In 2001 patient was operated for squamous cell carcinoma on the left side of the tongue. Before preoperative radiation therapy, small residual mandibular dentition was removed because of its poor prognosis. Radiation dose on mandible was 57-66 Gy. After tumor surgery patient received conventional complete dentures. Ten years later, the patient was referred again to the Turku University Central Hospital due to constant ulceration under the mandibular denture. The residual ridge of the mandible was severely resorbed. Patient's existing lower complete denture was replaced with a milled bar-retained overdenture on four implants. Treatment turned out to be challenging due to severely restricted tongue movement and tissue defects. PMID- 29797850 TI - ? PMID- 29797849 TI - Social gradient in intermediary determinants of oral health at school level in Finland. AB - OBJECTIVE: An adapted framework for oral health inequalities suggests that structural determinants cause oral health inequalities through socio-economic position (SEP) and intermediary determinants. We applied this framework to examine whether there is a social gradient in the intermediary determinants at the school level, even when adjusted for school size, geographical location and teaching language. BASIC RESEARCH DESIGN: Cross-sectional survey. METHODS: This study combined data from two independent studies focusing on Finnish upper comprehensive schools (N=970): the School Health Promotion study (SHPS) and the School Sweet Selling survey (SSSS). All schools that took part in the SSSS and whose pupils answered the SHPS were included in the analysis (n=360, response rate=37%). From the questions of the SHPS and the SSSS suitable for the theoretical framework, attitudes and access to intoxicants, school health services, school environment, home environment, the school's oral health-related actions and the pupil's own behaviour were selected as the intermediary determinants and as the factors determining the school-level SEP. The social gradient in the intermediary determinants of oral health was investigated with Pearson's and Spearman's correlation coefficients between those and the school level SEP. In the multivariable analysis, the General Linear Model with manual backward elimination was used. RESULTS: A social gradient was observed in the intermediary determinants 'home environment' and 'the pupils' tooth brushing frequency' and an inverse social gradient in 'attitudes and access to intoxicants' and 'school health services'. CONCLUSIONS: Social gradient between schools could increase Finnish adolescents' oral health inequalities. PMID- 29797851 TI - [Myocardial fibrosis detected by cardiac MR : A substrate for ventricular arrhythmias and sudden cardiac death]. AB - Myocardial fibrosis often develops in the setting of hypertrophic and dilated cardiomyopathies (CMP), but is also a common sequela after inflammatory CMP or following an acute myocardial infarction in patients with coronary artery disease. Cardiac magnetic resonance (CMR) provides a precise quantification of mass and spatial distribution of myocardial fibrosis by the so-called " late gadolinium-enhancement " (LGE) technique and current evidence is provided in this article linking fibrosis mass to outcome in these specific patient populations. The position of CMR fibrosis imaging in the current guidelines is discussed and suggestions are given how to integrate CMR fibrosis imaging in the work-up and risk stratification of these patient populations. Finally, a short outlook is given on anticipated developments on CMR fibrosis imaging and its integration into patient management. PMID- 29797852 TI - [Therapeutic options in advanced heart failure : place of durable left ventricular assist device (LVAD)]. AB - Despite the benefit of the drugs acting on neuro-humoral activation and cardiac resynchronization therapy, some patients will end in a severe refractory form of heart failure: advanced heart failure. The only therapeutic options with a positive impact on mortality and quality of life are heart transplantation and permanent left ventricular assist device (LVAD). The significant technological improvements of the past 20 years lead to a reduction of the complications associated with these devices, which now allow their use not only during the waiting period preceding heart transplantation (bridge to transplant), but also as a durable therapeutic option (destination therapy). PMID- 29797853 TI - [ECG : interpretation and clinical significance of P-wave abnormalities]. AB - The ECG provides information about heart rhythm and myocardial integrity, including the atria. The sinus P wave exhibits a 0-90 degrees axis and a generally biphasic morphology in lead V1. An amplitude >2 mm in lead II and >1 mm in lead V1 is a specific sign of right atrial enlargement, often related to pulmonary disease or pulmonary hypertension. Interatrial block (IAB) is defined as a P-wave >=120 ms with, in the advanced form, a biphasic morphology in inferior leads. It is most commonly seen in the context of advanced age, cardiovascular risk factors, coronary artery disease or valvulopathies. IAB is a risk factor for supraventricular tachyarrhythmias, stroke, left ventricular dysfunction and mortality. The identification of a P-wave abnormality has prognostic implications and should trigger the search for associated conditions. PMID- 29797854 TI - [Diagnosis of myocardial infarction in patients with cardiac pacing]. AB - Diagnosis of an acute coronary syndrome in patients with cardiac pacing can be difficult, as the usual ECG criteria for ischemia may not apply in case of a ventricular paced rhythm. This article discusses the ECG modifications observed in this setting, as well as in case of previous myocardial infarction. In addition, we discuss the phenomenon of cardiac memory, which may lead to erroneous diagnosis of myocardial ischemia. PMID- 29797855 TI - [Patent foramen ovale closure : update]. AB - The question of whether to perform percutaneous PFO closure to reduce the risk of recurrent ischemic stroke has been a dilemma for many years. Recent randomized trials have shown the superiority of percutaneous closure compared to medical therapy for large shunts. The indication of PFO closure is based on a multidisciplinary decision involving neurologists, cardiologists and hemostasis specialists. Important points are: PFO anatomy, brain imaging, history of venous thromboembolism and potential thrombophilia. In addition, atrial fibrillation (AF) should systematically be excluded. The intervention is performed under fluoroscopic guidance alone or with additional echocardiographic guidance. The procedural complication rate is low. There is an increased incidence of AF after percutaneous closure compared with medical therapy. PMID- 29797857 TI - ? PMID- 29797856 TI - [TAVI in 2018 : new indications and open questions]. AB - The last years, various large randomized studies have demonstrated the benefit of TAVI (transcatheter aortic valve implantation) over medical therapy or over conventional surgical treatment in inoperable or very high risk patients with symptomatic severe aortic stenosis. More recently, new data has also shown that among patients at intermediate risk, TAVI is at least as beneficial as surgical valve replacement. In this article, we will focus on the new recommendations of the European society of cardiology but also on issues that remain open. PMID- 29797858 TI - ? PMID- 29797859 TI - ? PMID- 29797860 TI - ? PMID- 29797861 TI - ? PMID- 29797863 TI - ? PMID- 29797862 TI - ? PMID- 29797864 TI - ? PMID- 29797865 TI - Demonstration of a laparoscopic structured-illumination three-dimensional imaging system for guiding reconstructive bowel anastomosis. AB - This paper reports the development and system analysis of a laparoscopic system based on structured illumination technique capable of three-dimensional (3-D) reconstruction of porcine intestine during surgical anastomosis (connection of tubular structures). A calibration target is used to validate the system performance and results show a depth of field of 20 mm with an accuracy of 0.008 mm and precision of 0.25 mm. The imaging system is used to reconstruct a quantitative 3-D depth measurement of ex vivo porcine bowel tissues to mimic an end-to-end bowel anastomosis scenario. We demonstrate that the system can detect a suture in the tissue and map homogeneous surfaces of the intestine with different tissue pigments, affirming the feasibility for depth quantization for guiding and assisting medical diagnostic decisions in anastomosis surgery. PMID- 29797866 TI - Adaptable switching schemes for time-encoded multichannel optical coherence tomography. AB - We introduce the approach of variable time encoding for multichannel optical coherence tomography (OCT). High-speed fiber optical switches are applied for sequential sample arm switching to enable quasisimultaneous image acquisition from three different orientation angles. In comparison with previous multichannel OCT (using simultaneous sample illumination), time-encoded multichannel OCT has no need for division of illumination power among the respective channels to satisfy laser safety requirements. Especially for ophthalmic applications-in particular retinal imaging, which the presented prototype was developed for-this advantage strongly influences image quality through an enhanced sensitivity. Nevertheless, time encoding comes at the cost of a decrease in imaging speed due to sequential channel illumination. For the typical multichannel OCT modality Doppler OCT, this results in a reduction of the maximum unambiguously determinable Doppler velocity. However, we demonstrate that this drawback can be overcome by adaptation of the illumination channel switching scheme. Thus, a re extension of the maximum unambiguously determinable Doppler frequency to the full A-scan rate of the tunable light source is presented. The performance of the technique is demonstrated by flow phantom experiments and measurements of retinal blood flow in the eyes of healthy human volunteers. PMID- 29797867 TI - [Latitudinal trends in foliar delta13C and delta15N of Quercus variabilis and their influencing factors.] AB - We aimed to reveal the latitudinal trends in foliar delta13C and delta15N of Quercus variabilis, a widely distributed species in East Asia, associated with two ontogenetic stages (juvenile and mature trees) along a North-South transect (26 degrees -40 degrees N). The results showed that mature trees had higher foliar delta13C and delta15N values than juveniles. Foliar delta13C and delta15N values of trees with both ontogenetic stages were nonlinearly increased and decreased with latitude, respectively. No interaction between ontogenetic stage and latitude for the changes of foliar delta15N and delta13C indicated that both ontogenetic stages across the transect consistently responded to latitudinal environmental variations. Results from the random forest models indicated that foliar delta15N of Q. variabilis was mainly affected by soil nutrient contents, e.g., soil organic matter, phosphorus, nitrogen, whereas dominated factors for foliar delta13C were related to moisture, such as relative humidity, precipitation of growing season. PMID- 29797868 TI - [Water utilization characteristics of the degraded poplar shelterbelts in Zhangbei, Hebei, China.] AB - In Zhangbei County, Hebei Province, poplar-dominated shelterbelts are degraded to different extents. Water availability is the main limiting factor for plant survival in arid areas. The purpose of this study was to reveal the relationship between water availability and poplar degradation. Based on the hydrogen and oxygen stable isotope techniques, we explored the water sources of Populus simonii under different degradation degrees by comparing the isotopic values of P. simonii xylem water with that in potential water source, and calculated the utilization ratio of each water source. The results showed that the water sources of poplar trees varied with degradation degree. The water sources of P. simonii gradually transferred from the deep layer to the surface layer with the increases of degradation. P. simonii with no degradation mainly absorbed soil water in the range of 320-400 cm, with the utilization rate being 25.1%. P. simonii with slight degradation mainly used soil water at depth of 120-180, 180-240 and 240 320 cm. The total utilization rate of three layers was close to 50.0%, with less utilization of water from other layers. The moderately degraded P. simonii mainly used soil water at depth of 20-40, 40-60 and 60-80 cm. The utilization rate of each layer was 17.5%-20.9%, and the contribution rate of soil water under 120 cm was less than 10.0%. The severely degraded P. simonii mainly used water from surface soil layer (0-20 cm), with the utilization rate being 30.4%, which was significantly higher than that of other water sources. The water sources of poplar shelter forests were gradually shallower during the process of degradation. However, the low soil water content in the shallow layer could not meet the normal water demand of poplar, which would accelerate the degradation and even decline of poplar. PMID- 29797869 TI - [Effects of biochar addition on the mineralization of native soil organic carbon in Cunninghamia lanceolata plantation.] AB - Effects of addition of different biochars on soil organic carbon (SOC) mineralization were studied by the 13C-labelling technique for a better understanding of biomass resource utilization and carbon sequestration in subtropical Chinese fir (Cunninghamia lanceolata) plantation. An incubation experiment under 25 C was performed over a period of 112 days to address how different biochar addition would affect the mineralization of native SOC. Biochars were produced from Schimasuperba or C. lanceolata litter at 350, 550 and 750 C, respectively. Results showed that the mineralization of native SOC was significantly accelerated during the first three days and subsequently suppressed from 7 to 112 days of incubation after C. lanceolata biochar addition compared to the control. In the S. superba biochar addition treatment, there was a significant increase in mineralization of native SOC within the first 14 days of incubation and then a rapid decrease from days 28 to 112. After 112 days incubation, all the three C. lanceolata biochar (350, 550 and 750 C) additions significantly inhibited the mineralization of native SOC. A similar trend was observed for the two S. superba biochar (350 and 550 C) additions but not for the S. superba biochar (750 C) addition. The decomposition rates of S. superba biochar and C. lanceolata biochar were 0.8%-2.8% after 112 days incubation and decreased with the increases of pyrolysis temperature. Under the same pyrolysis temperature, the decomposition rate of the S. superba biochar was significantly higher than that of the C. lanceolata biochar. In conclusion, both the raw material and pyrolysis temperature of biochars would be important factors driving the mineralization of native SOC and biochar degradation. PMID- 29797871 TI - [Effects of alpine meadow degradation on soil carbon, nitrogen, and carbon stable istope in Zoige Plateau.] AB - To investigate the differences of soil carbon, nitrogen, and carbon stable isotopes in Zoige wetland, we analyzed the abundance of carbon stable isotopes and the contents of carbon and nitrogen in soils of three kinds of retrogressive successional grasslands (swampy meadow, steppe meadow, and degraded meadow). The results showed that the delta13C values in the meadow soil of Zoige alpine wetland ranged from -26.210/00 to -24.720/00. The abundance of delta13C increased with the depth of soil. There was a significantly negative relationship between delta13C values and logarithm of soil organic carbon content across the soil profile. The delta13C values in the surface soil (0-10 cm) followed the order of grassland meadow>degraded meadow>swampy meadow, and the beta values followed the order of grassland meadow>swampy meadow>degraded meadow. Soil organic carbon content was 105.32, 42.11 and 31.12 g.kg-1, while nitrogen content was 8.74, 3.41 and 2.81 g.kg-1, and C/N was 11.26, 11.23 and 10.89, in the swampy meadow, grassland meadow and degraded meadow, respectively. The soil C/N was lower in degraded meadow than that in swampy meadow and grassland meadow. The total organic carbon and nitrogen content decreased obviously with increasing soil depth. The variations of soil delta13C among meadows with different degradation stages were mainly restricted to the 0-10 cm soil layer. The beta values and C/N were the lowest in degraded meadow among three stages, suggesting that the mineralization rate of degraded meadow soil organic matter was relatively fast. PMID- 29797870 TI - [Allocation of rice photosynthates in plant-soil system in response to elevated CO2 and nitrogen fertilization.] AB - To examine the allocation of rice photosynthates and its response to the elevated CO2 (800 MUL.L-1) and N fertilization (100 mg.kg-1) at both tillering stage and booting stage in plant-soil system, rice was continually labelled with 13CO2. The results showed that the rice root biomass at the tillering stage and the shoot biomass at the booting stage were significantly increased under elevated CO2. Elevated CO2 increased the rice biomass and root-shoot ratio at tillering stage, but reduced it at booting stage. Under elevated CO2, N fertilization promoted shoot biomass during rice growth, but significantly decreased the root biomass at booting stage. Elevated CO2 significantly increased the allocation of assimilated 13C to the soil at the booting stage. N fertilization did not promote the elevated CO2-induced stimulation of assimilated 13C allocated to the soil, and it even decreased the proportion of assimilated 13C in the soil. In summary, elevated CO2 increased the photosynthetic C allocation into soil and promoted the turnover of soil organic carbon in paddy soil. N fertilization enhanced rice shoot biomass but decreased the belowground allocation of photosynthetic C. PMID- 29797872 TI - [Effects of different fulvic acid application rates on fruit yield, quality and fate of 15N-urea in 'Red General' apple.] AB - To explore the effects of different fulvic acid application rates on 15N-urea absorption, utilization, residue amount, loss and fruit yield and quality, fifteen-year-old 'Red General'/ Malus micromalus Makino was selected as experiment material by using the 15N-labeled tracer technique. Five treatments were established: single urea (CK), combination of urea and fulvic acid with varied rates (NF1, NF2, NF3 and NF4 represented 75, 150, 300 and 450 kg.hm-2 fulvic acid application rates, respectively). The main results were as follows: the 15N derived from fertilizer (Ndff) in root, one-year-old branch and leaf were displayed with an order of NF3>NF4>NF2>NF1>CK at the fruit maturity stage, and significant difference was observed in Ndff value among the five treatments. The total N content and 15N absorption amount were highest in NF3, followed by NF4, and lowest in CK. Compared with CK, the 15N utilization rate in NF1, NF2, NF3 and NF4 was increased by 14.2%, 33.5%, 64.2% and 50.0%, and the 15N loss rate was decreased by 9.1%, 18.5%, 37.1% and 28.7% respectively. The residue amount of 15N urea varied across different treatments, and that in 0-60 cm soil layer under combination of urea and fulvic acid was significantly higher than CK, with the highest value occurred in NF3, while it was lower than CK in 60-100 cm soil layer. In comparison with CK treatment, the largest increment of yield per plant and net income appeared in NF3, with an enhancement of 15.8% and 20.2%, respectively. In addition, the fruit hardness, soluble solid and sugar-acid ratio reached the highest value in NF3. Considering the responses of fruit yield and N utilization efficiency, the suitable fulvic acid application rate was 326.41 350.61 kg.hm-2. PMID- 29797873 TI - [Effects of controlled-release nitrogen fertilizer and bag-controlled release fertilizer on utilization of 15N-urea in 'Orin' apple and its accumulation in soil.] AB - Taking a six-year old 'Orin' apple tree plantation ('Orin'/SH6/ Malus micromalus Makino) as test material, the effects of common urea treatment (CU), bag controlled release ferti-lizers treatment (BCRF) and controlled-release nitrogen fertilizer treatment (CRNF) on 15N-urea absorption, utilization, loss and accumulation dynamics of nitrogen content in 0-80 cm soil layer were investigated by 15N labeled tracer method. The results showed that compared with CU treatment, both CRNF and BCRF treatments increased the inorganic nitrogen content in soil at the late stage of apple growth, the leaf SPAD value, leaf nitrogen content, net photosynthetic rate and 15N derived from fertilizer (Ndff value) of different organs at fruit maturity stage, with CRNF showing stronger effects than BCRF. The amount of 15N residue in 0-40 cm soil layer showed a decreasing trend in different phenological stages. The amount of 15N residue was the highest in CRNF, followed by BCRF, and the lowest in CU, among which CRNF declined gently with 15N residue mainly concentrated in the 0-40 cm soil layer. 15N residue in 40-80 cm soil layer showed an increasing trend in different phenological stages, which was the highest in CU, followed by BCRF, and the lowest in CRNF, and that of CRNF increased gently. The 15N fertilizer utilization rate of CRNF was 32.6% at fruit maturity stage, which was 1.11 and 1.56 times as high as that of BCRF and CU, whereas its 15N loss rate was 21.6%, being obviously lower than BCRF (35.6%) and CU (59.6%). CRNF significantly improved fruit yield and quality and increased economic benefits. PMID- 29797874 TI - [Nitrogen application technology in dwarfed apple trees.] AB - 15N trace technique was used to explore the characteristics of 15N-urea absorption, utilization, loss and fruit quality of eight-year-old 'Yanfu3'/M26/Malus hupehensis Rehd. seedlings. There were three different nitrogen fertilization treatments: one-time nitrogen application in spring (1), two times nitrogen application (2), the intensive technique of nitrogen application with several times application and reduction in amount (3). The results showed that leaf area, chlorophyll content (SPAD value), photosynthetic rate (Pn), total N content of leaves and the total biomass per plant (except fruit), as well as the root-shoot ratio of treatment 3 were obviously higher than those in the treatments of 1 and 2. Treatment 3 significantly increased the protective enzymes (SOD, POD and CAT) activities and decreased the malondialdehyde (MDA) content in leaves. Significant differences were found on the 15N derived from fertilizer (Ndff value) of different organs, with the fruit Ndff showing the highest, followed by the one-year-old branches, leaves and roots of the three treatments. The Ndff values of each organ were the highest in the treatment 3. At fruit maturity stage, total N content of plant in treatment 3 was 93.0 mg.kg-1, which was obviously higher than that in the treatments 1 (70.2 mg.kg-1) and 2 (81.9 mg.kg-1). 15N nitrogen utilization ratio of treatment 3 was 33.6%, which was obviously higher than that in the treatments 1 (20.4%) and 2 (26.0%). The 15N loss rate was 46.9% in treatment 3, being obviously lower than that in the treatments 1 (56.5%) and 2 (52.9%). There were significant differences of fruit mass, soluble solid, fruit firmness, soluble sugar content, titratable acids and sugar-acid ratio among different treatments, with the highest values in the treatment 3 and the lowest values in treatment 1. PMID- 29797875 TI - [Effects of different phosphorus application rates on growth, 15N-urea absorption, and utilization characteristics of pear rootstocks.] AB - Three kinds of potted one-year-old pear rootstocks (Pyrus calleryana, P. pashia, and P. xerophila) and 15N trace technique were used to examine the effects of different phosphorus application rates (P0, P1, P2, P3 and P4 equivalent to 0, 50, 100, 150 and 200 kg.hm-2 P2O5, respectively) on plant growth and the characteristics of 15N-urea absorption and utilization. The results showed that, with the increases of phosphorus levels, plant height, ground diameter, dry mass, root surface area, root length, number of root tips, root activity, root respiration rate, Ndff values, and nitrogen use efficiency of rootstocks first increased and then decreased. However, the range of rise and fall of different rootstocks were distinct, and each index reached the highest level at different phosphorus levels. The plant height, diameter, dry mass of P. xerophila were the highest under the same phosphorus level, followed by P. pashia, and P. calleryana was the lowest. The root architecture parameters and root respiration rate showed the same trend, but Ndff values and nitrogen use efficiency performed different. Under different phosphorus levels, each index of P. xerophila reached the highest level at P3, but those of P. pashia and P. calleryana appeared at P2 and P1 rates, respectively. The Ndff values in stem were the highest among different organs of rootstocks at diffe-rent phosphorus levels, and the highest nitrogen use efficiency of P. xerophila, P. pashia and P. calleryana was 9.6%, 8.9% and 8.3%, respectively. The variations of plant growth and N absorption and utilization of different pear rootstocks across different phosphorus levels indicated that phosphorus fertilizer should be carry out reasonably in practice and give full consideration of phosphorus demands of plants. PMID- 29797876 TI - [Characteristics of absorption, utilization, and distribution of 15N-urea for Korla fragrant pear in spring.] AB - Six-year-old Korla fragrant pear trees were fertilized with 15N-labelled urea before early bud stage to examine the absorption, distribution, and utilization of urea. Results showed that there was a significant difference of 15N distribution rate in organs at different growth stages. 15N was pre-ferentially distributed in the roots , with Ndff (15N amount absorbed from the fertilizer contribution rate of the total nitrogen organ) being the highest in roots following by new shoots at full-bloom stage. During new shoot growing and fruit expanding stages, 15N absorbed in roots preferentially moved to new organs (leaves and new shoots), with 15N distribution rate to roots being continuously decreased. Fruits became the new distribution center with highest Ndff at harvest stage. The amounts of absorbed 15N in fruits accounted for 19.8% of total absorbed 15N in the tree. The utilization rate of 15N-labelled urea at current season increased gradually with the growth stages. The maximum value of utilization rate was 18.5%, which was observed at harvest stage. PMID- 29797877 TI - [Key pathway of methane production and characteristics of stable carbon isotope of the Tuojia River waterbody.] AB - This study aimed at exploring the key pathway of methane production and clarifying the composition and distribution of carbon (C) isotopes in the Tuojia River waterbody in Hunan Pro-vince. We estimated CH4 concentrations and fluxes of four reaches (S1, S2, S3 and S4) by a two-layer diffusion model and gas chromatography. The spatial and temporal distribution of CH4 flux and its relationship with environmental factors were examined. The key pathway of CH4 production was investigated by stable C isotope method to analyze the distribution characteristics of 13C isotope (delta13C) of water dissolved CH4 and seston/benthic organic matter. There was significant seasonal variability in water pH, with mean value of (7.27+/-0.03). The concentration of dissolved oxygen (DO) showed strong seasonal and spatial variations, with the range of 0.43-13.99 mg.L-1. The maximum value of DO occurred in S1 and differed significantly in summer and autumin. In addition, DO differed significantly in winter and other seasons in S2, S3 and S4. The concentration of dissolved organic carbon (DOC) showed a gradual increasing trend from source to estuary. The highest concentration of DOC (8.32 mg.L-1) was found in S2, while the lowest was observed in S1 (0.34 mg.L-1). The electrical conductivity (EC) and oxidation-reduction potential (ORP) of water ranged from 17 to 436 MUS.cm-1 and from -52.30 to 674.10 mV, respectively, which were significantly different among the four reaches (P<0.05). Water ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) concentrations were in the ranges of 0.30-1.35 (averaged 0.90+/-0.10) mg.L-1 and 0.82-2.45 (averaged 1.62+/-0.16) mg.L-1, respectively. The dissolved concentration and diffusion flux of CH4 ranged from 0 to 5.28 MUmol.L-1 and from 0.34 to 619.72 MUg C.m-2.h-1, respectively, with significant temporal and spatial variations. They showed a similar trend among reaches. Their values were highest in spring, followed by in winter and lowest in summer and autumn. Spatially, the CH4 concentration and flux followed the order of S2>S3>S4>S1. The correlation analysis showed that CH4 flux was positively correlated with NH4+-N and DOC. The pathway of CH4 production of all reaches was dominated by acetic acid fermentation, while there were obvious differences among the four reaches. The contribution of CH4 from acetic acid fermentation was greatest (87%) in S1, followed by S4(81%), S2(78%) and S3(76%). The mean value of the delta13C for dissolved CH4, seston organic matter and benthic organic matter was -41.640/00+/ 1.910/00, -14.070/00+/-1.060/00 and -26.200/00+/-1.020/00, respectively. There was a positive correlation between the delta13C of dissolved CH4 and benthic organic matter, whereas the delta13C value of dissolved CH4 was negatively correlated with CH4 flux. PMID- 29797878 TI - [Temporal and spatial variations of hydrogen and oxygen isotopes in Tuojia River and its influencing factors.] AB - The characteristics of hydrogen and oxygen stable isotopes in river is important for regional hydrologic cycle research. To uncover water supply sources in subtropical agricultural basin from a perspective of stable isotopes, field measurements were conducted in four reaches (S1, S2, S3 and S4) of Tuojia River from April to August 2017. We analyzed the spatial and temporal variations in hydrogen and oxygen isotopes and deuterium excess parameters and their relationship with precipitation, altitude and water quality. Results showed that hydrogen and oxygen isotopes and deuterium excess values ranged from -43.170/00 to -26.430/00 (-35.500/00+/-5.440/00), -7.940/00 to -5.700/00 (-6.860/00+/ 0.740/00), and 16.770/00 to 23.490/00 (19.390/00+/-1.950/00), respectively. Under the influence of monsoon circulation, hydrogen and oxygen isotopes showed substantial seasonal variation, with spring (deltaD: -29.880/00+/-3.310/00; delta18O: -6.180/00+/-0.570/00) > summer (deltaD: -39.250/00+/-2.650/00; delta18O: -7.320/00+/-0.420/00). The spatial distribution of hydrogen and oxygen isotopes values increased fluctuantly with the position from the sampling site to the river's source, with deltaD: S1P4 (0.876)>P3 (0.726)>P1 (0.653)>P5 (0.628). Tr was significantly positively correlated with the daily maximum temperature (Tmax), daily mean solar radiation (SR), daily mean saturated vapor pressure deficit (VPD), potential evapotranspiration (PET), and daily mean soil water potential (Psi), but negatively correlated with the daily mean air relative humidity (RH), daily precipitation (P), and daily minimum temperature (Tmin). According to the upper boundary line ana-lysis, significant differences were found in the degree of Tr responding to each single environmental factor among slope positions. The degree of its responses gradually decreased for average daily air temperature (T), RH, VPD, PET and Psi, whereas increased for the SR and daily average volumetric soil water content (VSM) from the upper position to the lower. Results from regression and partial correlation analysis showed that variation of Tr was mainly controlled by VPD, PET and RH in different slope positions. Tr was also strongly affected by Psi and T in the upper-slope positions and by SR, Tmin and VSM at the lower-slope positions. Generally, the Tr difference among slope positions was a consequence of joint contributions of soil water and meteorological factors. It is necessary to consider the changes of soil water and meteorological factors in different positions along the slope when examining slope-scale or watershed-scale forest transpiration with sap flow estimated from xylem sap flux density measurements of a particular plot. PMID- 29797884 TI - [Composition and seasonal dynamics of seed rain in Chinese fir (Cunninghamia lanceolata) plantation.] AB - Chinese fir plantation is an important part of the subtropical forests in southern China. It has a sustainable natural regeneration ability, which is the foundation of determining community succession direction and maintaining their large area. The main objective of this study was to investigate whether the seed pool was the main restricting factor for the natural regeneration of Chinese fir plantation. Mixed broad leaf-conifer forest and pure plantation of Chinese fir were selected to study the species composition, quantity and seasonal dynamics of all species and dominant species. The results showed that seeds from 21 species belonged to 13 families and 18 genera were collected in the mixed forest, while seeds from 19 species belonged to 12 families and 16 genera were collected from pure forest. Seed rain intensities of all species were 3797 and 3300 seeds.m-2 in mixed forest and pure plantation, respectively. The number of seeds from tree species was absolutely dominant in seed rain (mixed forest 89.1%, pure plantation 86.2%). The number of Chinese fir seeds was the largest, the intact seeds intensities were 825 and 345 seeds.m-2, respectively. The proportion of all types of seeds in both stands followed the order: the intact seeds > empty or rotten seeds > feeding seeds. The seed rain of both stands had significant seasonal dynamics, both reaching the peak in autumn. The seed rain mainly was intact seeds at the peak of seed-falling. Both mixed forest and pure plantation of Chinese fir had plenty of seeds. The results indicated that the seed rain is not the main factor that restricts natural regeneration in Chinese fir plantations. PMID- 29797885 TI - [Effects of temperature and moisture on net ecosystem CO2 exchange over a meadow wetland in the Horqin, China.] AB - Using the eddy covariance technique, the Bowen-ratio meteorological and soil monitoring system, we analyzed the CO2 flux dynamics and its responses to temperature and moisture over a meadow wetland in the Horqin during the growing season (from May to September) in 2016. The results showed that the accumulated net ecosystem CO2 exchange (NEE) was -766.18 g CO2.m-2 during the growing season. The gross primary productivity (GPP) and ecosystem respiration (Re) were 3379.89 and 2613.71 g CO2.m-2, respectively. The ratio of Re to GPP was 77.3%, indicating that this ecosystem was an obvious carbon sink. The average diurnal variation of NEE exhibited a single peak U-shaped curve with an absorption of CO2 from May to mid August and a release of CO2 from late August to September. Daytime NEE well fitted with the photosynthetically active radiation (PAR) by a rectangular hyperbolic function. Meanwhile, the relationship was affected by the environmental factors, including vapor pressure deficit (VPD), soil water content (SWC) and air temperature (Ta). Regression analysis showed that the VPD and SWC for the maximum daytime NEE were 1.75 kPa and 35.5%, respectively. Daytime NEE increased with Ta, and with no inhibitory effect on the daytime NEE when it reached the maximum. Nighttime NEE had an exponential relationship with soil temperature (Ts). During the entire growing season, the temperature sensitivity of the ecosystem respiration (Q10) was 2.4, which was negatively related to SWC. The nighttime NEE was controlled by both Ts and SWC. PMID- 29797886 TI - [Carbon, nitrogen and phosphorus contents and their ecological stoichiometry in litters and soils on meadow of Wugong Mountain, Jiangxi, China at different altitudes.] AB - Carbon (C), nitrogen (N) and phosphorus (P) contents and ecological stoichiometry and their correlations of litter and soil along 1500-1900 m on Wugong Mountain meadow were studied. The results showed that litter C, N and P contents varied in the range of 397.5-458.24, 11.59-17.12, 1.05-2.19 mg.g-1, respectively. Litter C content decreased, and the contents of N and P decreased first and then increased with the increases of altitude. Soil C, N and P contents varied in the range of 51.64-80.01, 3.30-4.77, 0.44-1.09 mg.g-1, respectively. Soil C, N and P contents first increased and then decreased with the increases of altitude. However, soil P varied much less along the altitude gradient. Litter C:N, C:P and N:P varied in the range of 24.73-40.36, 203.65-463.08, 7.16-13.80, respectively, and first increased but then decreased with altitude. Soil C:N, C:P and N:P were 14.95 16.95, 56.87-162.52, 3.69-10.58, respectively. Soil C:N changed little with altitude. Soil C:P and N:P first increased and then decreased with increa-sing altitude, with the maximum presented at 1600-1700 m. Changes in soil C, N and P contents differed between litter and soil on Wugong Mountain meadow. The mean C, N and P contents as well as C:N, C:P and N:P in litter were higher than those in soil. PMID- 29797887 TI - [Geostatistical analysis on the spatial pattern of Quercus mongolica population in different communities.] AB - Taking Quercus mongolica population in the secondary forest of Q. mongolica as the research object, two plots in different stages of succession (A and B) were set up in Tazigou Forest Farm of Wangqing Forestry Bureau, Jilin Province. By applying the method of adjacent grid survey, each plot was divided into 100 units of 10 m*10 m and the spatial coordinates of each tree in the unit were accurately located to survey all the basic information of trees with diameter at breast height (DBH)>=1 cm. The degree, composition, scale and pattern of spatial heterogeneity of individual tree of Q. mongolica were analyzed by means of semi variance function and fractal dimension of geostatistics. By using Kriging interpolation method, unbiased estimation of tree attribute with spatial autocorrelation was carried out, distribution map was drawn and spatial distribution pattern was analyzed. The results showed that the best semi-variance function of tree attributes in two plots was mainly distributed in an exponential model and a spherical model with an aggregated distribution. The degree of spatial autocorrelation and continuity of plot A were higher than that of plot B. The DBH and the east-west crown (CEW) had strong spatial heterogeneity and autocorrelation in the two plots. The tree attributes of both plots showed strong spatial heterogeneity in the north-south direction. In addition, there was strong spatial heterogeneity in the northwest-southeast direction of plot A and in the northeast-southwest of plot B. The strength of the spatial heterogeneity was higher and the scale being larger in plot A. The variations of DBH and CEW were obvious in plot A, while the variations of CEW and south-north crown (CSN) were obvious in plot B. The fractal dimension and semi-variogram function showed the same result. The tree attributes of plot A were mainly patchy and stripe, and the variation trend of spatial distribution pattern was obvious. The tree attributes of plot B was broken, with complex pattern. Those results indicated that the characteristics of population, community development, spatial scale and spatial horizontal direction might affect the spatial pattern of populations. The geostatistical analysis method is helpful to quantitatively and directly describe population growth and development trend, which can provide a theoretical basis for the sustainable management of Q. mongolica secondary forests in Northeast China. PMID- 29797889 TI - [Influence of rainwater harvesting and soil anti-seepage on soil water infiltration, distribution and use efficiency in hilly orchard.] AB - Rainwater harvesting and soil anti-seepage technology is a new technology based on the ridge film mulching and furrow rainwater harvesting. To explore the application effects of rainwater harvesting and soil anti-seepage technology, four different treatments including control (CK), loessal soil with compacted anti-seepage treatment (L1), red clay with anti-seepage treatment (R1), and red clay with compacted anti-seepage treatment (R2) were set up in a "Fuji" hillside orchard in Mizhi Demonstration Station of northern Shaanxi Province. Soil bulk density, stable infiltration rate, soil water content, fruit quality and yield, and water use efficiency were measured. Results showed that R2 had the best anti seepage efficiency with the highest bulk density (1.61 g.cm-3), the minimum water holding capacity, and the least stable infiltration rate (0.02 mm.min-1). The empirical formula of Kostiakov equation was suitable for describing water infiltration characteristics. Throughout the growing season, soil moisture for 0 60 cm soil depth in the rainwater harvesting ditch could be improved by the different anti-seepage treatments. R2 had the highest soil water content all the time and could satisfy the suitable water content standard for growth and development of apple trees in the dry season. Under the anti-seepage treatment, there was an "low humid layer" with 20-30 cm of soil layer under 60 cm soil depth, but the variation tendency of soil water content from "low humid layer" to 200 cm soil layer was stable and slightly higher than that in CK. Rainwater harvesting and soil anti-seepage treatments could increase fruit yield and water use efficiency, and improve the quality of fruit. Compared with that in CK, the fruit yield, the rate of good fruit, and water use efficiency of R2 treatment increased by 19.2%, 26.5%, and 24.5%, respectively. Therefore, rainwater harvesting and soil anti-seepage technology was recommended as the effective agricultural measurement in the apple production in loess hilly areas of northern Shaanxi Province. PMID- 29797888 TI - [Nondestructive detection of total nitrogen content in leaves of Santalum album based on ST-PCA-BP neural network.] AB - Nitrogen is one of the most important elements for plant growth. Producers often use a lot of nitrogen fertilizer during plant growth process. However, excessive fertilizer often cause ground-water pollution. In this study, we proposed a nondestructive testing method for total nitrogen content in leaves of sandalwood (Santalum album) based on ST-PCA-BP neural network. The results showed that, due to the wide color range of L*a*b* color system and its robustness in illumination change, images obtained from the field which were converted from RGB to L*a*b* color system had a satisfying segmentation result. The proposed ST-PCA-BP neural network was characterized by choosing variables through significance test (ST) and using variance inflation factor (VIF) and conditional index (CI) to analyze collinearity of results, and further using principal component analysis (PCA) to eliminate it. Such a method reduced the probability of the chance that BP neural network fell into the local minimum. Compared with the result of original data, data after ST processing, and data after PCA processing, the results of proposed method had the highest coefficient of determination, while the mean residual error and the root mean square error were the smallest. It was the best way to detect the total nitrogen content of sandalwood leaves with real-time and non destructive method. PMID- 29797890 TI - [Effects of microtopography on the pattern and association of dominant population.] AB - Different spatial distribution patterns and correlations could reflect the adaptation strategies of plant populations to different habitats. Geranium wilfordii and Gueldenstaedtia verna are the major species in the subalpine meadow. Within a field experiment, the Ripley K function was used to analyze the relationship of spatial distribution pattern and interspecific association between G. wilfordii and G. verna in different slope aspects. The results showed that soil water content and nutrient content gradually increased, whereas soil temperature and light intensity gradually decreased along the gradient from south to north slope. The distribution of G. verna and G. wilfordii showed significant differences in three slope aspects (north, west and south slopes). G. verna showed an increa-sing trend, while G. wilfordii showed a decreasing trend from north to south slope. On the north slope, G. verna populations showed aggregation distribution at 0-1.8 m scale, while the aggregation intensity weakened and tended to be a random distribution at 1.8-5.0 m scale. G. wilfordii populations showed aggregation distribution at 0-5.0 m scale. On the west slope, G. verna population showed aggregation distribution at the 0-1.2 m scale, and tended to be a random distribution at the 1.2-5.0 m scale. G. wilfordii population showed aggregation distribution at the 0-2.2 m scale, and tended to be a random distribution at the 2.2-5.0 m scale. On the south slope, G. verna and G. wilfordii population showed random distribution at the 0-5.0 m scale. Both species showed positive correlation at the 0-1.0 m scale but not at the 1.0-5.0 m scale on the north slope. G. verna and G. wilfordii were negatively associated at the 0-2.1 m scale but unrelated at the 2.1-5.0 m scale on the west slope. On the south slope, both species showed no correlation at the 0-5.0 m scale. PMID- 29797891 TI - [Assessment of the potential for urban facade greening in Xinjiekou District, Nanjing, China.] AB - Green facade is an important strategy to improve the urban eco-environment and reduce the negative effects of human activities in central districts of cities which are land-scarce and lack green spaces. We first summarized the limiting factors for the construction of green facades locally and internationally. Then, we used the Xinjiekou District of Nanjing City in China as a case study area, and selected the wind environment, solar environment, and physical build environment that might impact the potential development of green facades as key factors to quantitatively analyze singlely by geographic information systems (GIS) and computational fluid dynamics (CFD). Finally, the potential area to develop green facades was assessed through a multi-factor overlay analysis. The results showed that 17726 m2 of wall spaces in the Xinjiekou District had a high potential for facade greening, accounting for 30.8% of all exterior wall space under a height of 12 m and 17.3% of the entire study area. Sunlight was a key limiting factor in determining whether a green facade should be developed. Irrigation was identified as another important factor that might strongly affect the growth of vertical vegetation in urban environment. The spatial distribution of walls suitable for facade greening was uneven, with an "inner-high and south-high" spatial pattern. Our results would help to guide the design and development of green facades in Xinjiekou, and also provide a reference for planning and utilizing green wall space projects in other built and dense urban areas. PMID- 29797892 TI - [Long-term changes of land use/cover in the Three Gorges Reservoir Area of the Yangtze River, China.] AB - Understanding the temporal and spatial dynamics of land use/cover (LUC) can contri-bute to reveal the impacts of climate change and human activities on ecosystems and thus be an important prerequisite for ecosystem management. As an ecologically vulnerable area in China, the Three Gorges Reservoir Area (TGRA) of the Yangtze River presented significant complexity in the response to environmental changes. However, there is a general lack of understanding in the underlying mechanism. In this study, we interpreted the time series remote sensing images derived from the Landsat sensors to map the LUC of the TGRA, and aimed to analyze the long-term changes in the distribution and structure of LUC and elucidate the evolution process of LUC, which could provide a scientific basis to understand the complexity of ecosystem changes and regional ecosystem management in ecologically fragile regions. The results showed that the TGRA presented the significant changes in spatial heterogeneity of LUC structure from 1990 to 2015. Meanwhile, the landscape changed from farmland to woodland (forest and shrubland). Farmland decreased from 66.2% to 40.4%, but woodland increased from 31.3% to 53.5%, buildings and water area increased gradually. Forest gradually spread to the middle of the TGRA, while the buildings presented a scattered expansion. In the altitude zone of 500-1000 m and slope zone of 15 degrees -25 degrees , woodland increased noticeably, and the coniferous forest, mixed forest and shrubland had a higher growth rate. In the study period, due to the urban construction and the various ecological restoration projects in the TGRA, the LUC structure varied with the dam's impoundment and was characterized by the ecosystem restoration. Ecological restoration projects were helpful to reduce the negative impacts of urban construction and economic development on the environment. PMID- 29797893 TI - [Impacts of land use change on ecosystem services in the agricultural area of North China Plain: A case study of Shangqiu City, Henan Province, China.] AB - Under the rapid urbanization, quantitatively assessing the impacts of land use and cover change (LUCC) on ecosystem service is of great significance for regional ecological environment construction. Based on the land use maps of Shangqiu City (as the typical agricultural area of North China Plain) in the year of 1990, 2005 and 2015, the spatio-temporal dynamics of land use and ecosystem service were analyzed, and the impacts of LUCC on ecosystem services was quantified with the impact assessment model. The results showed that, from 1990 to 2015, farmland and construction land area, which covered more than 95% of the total area of the research area, changed the most in quantity as -104.38 and 201.59 km2 respectively, while forestland, grassland and water area changed the most by 79.3%, -73.7% and -24.2%, respectively. The total value of ecosystem service continuously decreased by 1.005 billion yuan, among which the value of hydrolo-gical regulation service suffered the most. The value of ecosystem service (ESV) presented an increasing trend in the west and a decreasing trend in the east. Extending from the center of the city to the outside, the value of ecosystem services was "high-low-high" in the east to west direction. The rate of farmland and water area contributed more than 95% to the total ecosystem service value, which had the greatest impact. The main drivers for the changes of land use and ESV in Shangqiu were population pressure, economic growth, regional policy, and urban planning. In the urban and rural development planning of Shangqiu City, more attention should be paid to the protection of na-tural resources and rational adjustment of the land use structure to realize sustainable development based on the harmony of economy, society and environment. PMID- 29797894 TI - [Delineation of urban development boundary based on the combination of rigidity and elasti-city: A case of Yiwu City in Zhejiang Province, China.] AB - Under the background of rapid urbanization, we took the contradiction between the rapid urbanization and resource environment protection as the starting point, conducted some theoretical research on urban growth boundary. Based on the definition of urban development boundary, we took Yiwu City, Zhejiang Province as a typical instance. Firstly, this study delimited the ecological boundary as ecological basic constraint area, using the methods of ecological red line discrimination and ecological sensitivity evaluation. Furthermore, the MCE-CA model was used in simulating the city size in 2020, making some adjustments to the moderate and low ecological-sensitive areas in the eco-sensitivity assessing, and delimiting the size of urban growth boundary and elastic control zones. The results showed that the ecological constraint area with a total area of385.2 km2 and outside of the ecological boundary was the security line of urban development and construction. The urban growth boundary with a total area of 163.3 km2 was not only the spatial boundary that could be constructed now, but also could meet the future development and construction. The district between the ecological boundary and urban growth boundary was an elastic control zone, in which urban development activities were allowed, but the size of construction could not exceed 8.5% of the total urban development boundary area. Our results delimited the urban development boundary under the rigidity and elasticity, which could guide the urban space development and provide a theoretical reference for China. PMID- 29797895 TI - [MODIS-driven estimation of regional evapotranspiration in Karst area of Southwest China based on the Penman-Monteith-Leuning algorithm.] AB - Karst area in southwestern China is characterized with complex topography, low soil water capacity, and fragile ecosystem. Accurate estimation of regional evapotranspiration is essential for ecological restoration and water resources management in southwestern China. Based on observed evapotranspiration and meteorological data, this study aimed to estimate spatial upscale evapotranspiration using the MOD15A2 LAI and Penman-Monteith-Leuning (PML) model, within which the stomatal conductance and soil wetness index were optimized by the least-square method. The results showed that the modeled ET well fitted with the observations, with the determination coefficient, Nash efficiency coefficient and RMSE being 0.85, 0.75 and 1.56 mm.d-1, respectively. The ET exhibited clear seasonality and reached to its maximum in summer, coinciding with vegetation phenology. The annual ET ranged from 534 to 1035 mm.a-1, with strong spatial heterogeneity which highly related to the precipitation. Evapotranspiration may be affected by precipitation as well as land use types. PMID- 29797896 TI - [Effect of meteorological factors on design farmland drainage modulus.] AB - Calculation of design drainage modulus is of great importance for the safety of farmland and reduction of waterlogging loss. We investigated the effects of main meteorological factors on design farmland drainage modulus by focusing on a closed farmland area in Ninghe District of Tianjin City. To resolve the problem of limited observation, the parameter sensitivity was analyzed according to mutual information and partial rank correlation coefficient aiming at the total runoff depth based on field observation experiment. The reasonable parameters were obtained by combining with soil water content and the relative variation of groundwater level. Then, a three-source runoff yield model coupling of excess infiltration and saturation was established to estimate runoff and design drainage modulus, and the effects of meteorological factors such as precipitation and evaporation on drainage modulus were analyzed. Results showed that summer precipitation significantly reduced and evaporation varied a little during 1960 2015. The corresponding drainage modulus decreased with the reduction of precipitation. When return period increased, the magnitude of the reduction in precipitation as well as the design drainage modulus increased. However, the effects of meteorological factors on design drainage modulus was generally inapparent. Thus, we concluded that the current drainage modulus is suitable for the study area. PMID- 29797897 TI - [Dynamics of nutrient concentration and microbial community composition during fine root decomposition in subtropical Mytilaria laosensis and Cunninghamia lanceolata plantations.] AB - We conducted a 12-month fine root decomposition experiment under 19-year-old Mytilaria laosensis and Cunninghamia lanceolate plantations to explore the dynamics of nutrient concentration and microbial community composition. The aim of this study was to provide insights into nutrient cycling under plantations with different tree species. Our results showed that the initial concentrations of phosphorus (P) and potassium (K) were significantly higher in the fine root of M. laosensis than those in C. lanceolata, which significantly decreased with decomposition. Nitrogen (N) concentration in fine roots of both species increased with decay time. The variation of N concentration in fine root of C. lanceolata lagged behind that in M. laosensis. During the decomposition, magnesium (Mg) concentration in fine root of C. lanceolata showed no significant changes, but that of M. laosensis decreased at the initial decay stage and increased thereafter and was significantly lower than that of C. lanceolata at the 8th month. The ratio of fungi to bacteria (F/B) of both species decreased at the initial stage and then increased, with significantly higher F/B in fine root of M. laosensis than that of C. lanceolate after one-year decay. Redundancy analysis (RDA) showed that changes in N and K concentrations and C/N ratio explained 37.2%, 14.5% and 14.8% of the variations in microbial community composition of C. lanceolata fine root respectively. However, during the decay of M. laosensis fine root, concentrations of Mg and K were key factors, accounting for 35.9% and 17.6% of the variations in microbial community composition, respectively. We concluded that other nutrients beyond N, such as Mg, might also be an important factor affecting root decomposition in different tree species. PMID- 29797898 TI - [Screening and phosphate-solubilizing characteristics of phosphate-solubilizing actinomycetes in rhizosphere of tree peony.] AB - A strain PSPSA1 with strong phosphate-solubilizing ability was isolated from the rhi-zosphere of tree peony. This strain was identified based on morphological characteristics, physiological and biochemical experiments, and 16S rDNA sequence analysis. Furthermore, its genetic stabi-lity and phosphate-solubilizing characteristics were investigated. Strain PSPSA1 was identified as the actinomycete Streptomyces albireticuli and showed high genetic stability. The order of phosphate solubilization capacity (PSC) in different phosphorus-source culture media was calcium phosphate (158.5 mg.L-1) > aluminum phosphate (139.9 mg.L-1) > ferric phosphate (127.7 mg.L-1) > lecithin (45.6 mg.L-1). The PSC and pH were significantly negatively correlated in inorganic phosphorus solution, but were not correlated in organic phosphorus solution. When using different carbon sources, PSC was in the order of lactose > glucose > maltose > fructose > sucrose > starch > cellulose. For different nitrogen sources, PSC was in the order of peptone > ammonium nitrate > ammonium sulfate > potassium nitrate > urea. Using glucose as a carbon source and peptone as a nitrogen source, strain PSPSA1 achieved the highest PSC of 202.6 mg.L-1. After incubated for 60 days, the available phosphorus content in soil with a single application of strain PSPSA1 increased by 68.2% compared with control, and the available phosphorus content in soil with mixed application of strain PSPSA1 and organic fertilizer increased by 76.7% compared with a single application of organic fertilizer. The results indicated that the strain PSPSA1 had a strong ability to dissolve insoluble phosphorus and its mixed application with organic fertilizer improved the phosphorus solubilization. Thus, PSPSA1 is a promising microbial resource for the production of high-efficiency biological phosphorus fertilizer. PMID- 29797899 TI - [Phyllosphere bacterial community structure of Osmanthus fragrans and Nerium indicum in different habitats.] AB - The diversity of phyllosphere bacteria is one of the hotspots in the research area of plant-microbial relationship. There are still a lot of controversies in the main factors influencing community structure of phyllosphere bacteria. In this study, the phyllosphere bacterial community structure of Osmanthus fragrans and Nerium indicum grown in three habitats was investigated based on high throughput sequencing and the main driving factors were examined. The results showed that there was no significant difference in phyllosphere bacterial diversity between the two plant species grown in three habitats. For phyllosphere bacterial community of two plant species from three habitats, the dominant phyla were Actinobacteria, Bacteroidetes, Chlamydiae, Cyanobacteria, Firmicutes and Proteobacteria, and the dominant genera included Methylobacterium, Sphingomonas, Hymenobacter, Polaromonas and Spirosoma. The structure of phyllosphere bacterial community was influenced by habitats, host species identity and species-habitat interaction, among which habitat showed the strongest effect. PMID- 29797900 TI - [Effects of protease inhibitors on the activities of midgut proteases in Callosobruchus chinensis (Linnaeus) larvae.] AB - To clarify the effects of protease inhibitors on the activities of midgut proteases in Callosobruchus chinensis (L.) larvae, the inhibitory effects of four kinds of protease inhibitors on the activities of midgut proteases of C. chinensis larvae were examined in vitro and in feeding conditions with indoor artificial insect inoculation. The activities of total protease, trypsin-like enzyme and chymotrypsin-like enzyme in the midgut of C. chinensis larvae fed on artificial mung bean that contained different contents of mung bean types in inhibitor (MBTI) were examined. The results showed that those four protease inhibitors had significant inhibitory effects on the activities of total protease, trypsin-like enzyme and chymotrypsin-like enzyme in C. chinensis larvae. The inhibitory effect was more significant when the concentration was higher. Among those inhibitors, the inhibitory effect of 20 MUg.mL-1 MBTI on three kinds of enzyme activities was the strongest, with reduction of 62.5%, 41.2% and 38.7%, respectively. Ovomucoid inhibitor (OI) had the lowest inhibitory effect. The activities of three enzymes in the midgut were also inhibited by C. chinensis larvae fed with artificial mung bean containing different inhibitors. The activities of three enzymes increased with the prolongation of the instar after feeding, but they were significantly lower than that in control. The inhibitory effect of MBTI was the strongest. The inhibitory effect on the activities of total protease and trypsin-like enzyme was gradually enhanced with the increases of MBTI contents when C. chinensis larvae were fed with artificial mung bean with different contents MBTI. The inhibitory effect on chymotrypsin like enzyme activity was not significant. When the content of MBTI was up to 20%, the activity of chymotrypsin-like enzyme was obviously inhibited. PMID- 29797901 TI - [Community structure of soil mites under Quercus variabilis forests in small watershed of karst area, Guizhou, China.] AB - To analyze the differences of community structure of soil mites between the rocky desertification environment and karst beech forests, we investigated the soil mites of Quercus variabilis forest in the Chaoying small watershed of Guizhou Province. Soil mites from 83 genera, 54 families, and 3 orders were collected in the four investigations of 2014. We analyzed the differences of genus numbers, individual numbers, individual density, Shannon diversity index (H), Margalef richness index (SR), Pielou evenness index (J), maturity index (MI) of predatory soil mites (Mesostigmata: Gamasina), community structure of the oribatid mites (MGP) and nutritional structure of mite. Results showed that Oribatida was dominant in taxonomic richness and individual abundance. Abundant genus, high individual density and diversity of soil mites were found in summer and autumn, and higher individual abundance was found in spring and autumn. Soil mites showed surface-aggregation in their distribution. Most predatory mites were K-selected in summer and r-selected in other seasons. The ecological groups of the oribatid mites were mainly P-type and O-type. Hypochthonius, Allobelba and Zygoribatula constituted the nutrient function group of the soil mites. There were significant differences in the main groups of soil mites in the beech forest and other forest types. Among all the groups, Parholaspididae, Laelapidae, Oppiidae and Haplozetidae with abundant genera composition, Multioppia, Parholaspulus, Scheloribates and Haplozetes with predominance could be used as a biological indicator for the soil environment in beech forests. PMID- 29797902 TI - [Degradation of nonylphenol in water by microorganisms immobilized on bamboo charcoal.] AB - Bamboo charcoal is a high-quality biochar, with a large surface area, well developed pores, and high mechanical strength. Therefore, it is one of the best choices of microbial immobilization carrier. In this study, the optimal preparation condition was examined for microorganisms immobilized on bamboo charcoal by the orthogonal test. The degradation effects of estrogen nonylphenol were compared between the bacteria immobilized on bamboo charcoal and free bacteria, and then feasibility of the reuse of immobilized bacteria was investigated. The results showed that lots of degrading bacteria could adhere to the surface and internal pores of bamboo charcoal. The optimum conditions for the preparation of immobilized microorganisms were as follows: 30 C, pH=7, 35-mesh bamboo charcoal. The degradation rate of nonylphenol was in good agreement with the first order kinetics equation. When the initial concentrations of nonylphenol were 30, 50, 80 and 100 mg.L-1, the degradation rates of nonylphenol of immobilized bacteria for seven days were 100%, 75.3%, 67.3% and 78.7%, respectively, which were significantly higher than those of free bacteria (54.2%, 51.5%, 30.6% and 23.5%). After eight rounds of reuse, the degradation rate for immobilized bacteria still reached as high as 36.5%, while it was only 8.9% for free bacteria. Our results indicated that the microorganisms immobilized on bamboo charcoal had long-term reusability, and thus had good prospects in the application of organic pollutants removal in wastewater. PMID- 29797903 TI - [Effects of Suaeda glauca planting and straw mulching on soil salinity dynamics and desalination in extremely heavy saline soil of coastal areas.] AB - To elucidate the seasonal variations in soil salinity and its driving factors, and to explore the effects of planting Suaeda glauca and straw mulching on soil desalination and salinity controlling, a field experiment was conducted in extremely heavy saline soil of coastal areas in Rudong, Jiangsu Province. There were four treatments: control (bare land, CK), planting S. glauca (PS), straw mulching A (at 15 t.hm-2, SM-A), straw mulching 2A (at 30 t.hm-2, SM-2A). Climate factors (including rainfall, atmospheric temperature, sunshine duration, and atmospheric evaporation) and soil salinity dynamic changes were determined from May 2014 to May 2015. Results showed that: (1) The seasonal variation of soil salinity was obvious in the bare ground (CK), with the lowest (8.69 g.kg-1) during June-August and the highest (26.66 g.kg-1) during September-December. The changes of soil salinity in topsoil (0-20 cm) were more intense than that in sub topsoil (20-40 cm), with the changes in sub-topsoil having somewhat time lag compared the topsoil. (2) Soil salinity in CK treatment had a significantly linear correlation with the cumulative rainfall and evaporation-precipitation ratio of the fifteen-day before sampling. The results from multifactor and interphase analysis indicated that the increases of rainfall would promote soil desalinization. The rise of atmospheric temperature could exacerbate soil salt accumulation in surface soil. The interaction between rainfall and atmospheric temperature would have a positive effect on soil salt accumulation. (3) PS treatment did not alter the seasonal variation in soil salinity, but it reduced soil salinity in topsoil. (4) In SM-A and SM-2A treatments, the relationship of soil desalinization rate (%, Y) and treatment time (days, X) was expressed as Logistic curve equation. Moreover, the soil desalination rate was over 95.0% in the topsoil after 90-100 days of straw mul-ching treatment and was over 92.0% in sub-topsoil after 120 days of straw mulching treatment. The soil salinity in SM-A and SM-2A treatments fluctuated below 0.60 g.kg-1 and 1.00 g.kg-1, respectively in topsoil and sub-topsoil. Considering the desalination and economic costs, a suitable amount of straw mulching (such as 15 t.hm-2) before rainy season was recommended, which would promote the soil desalinization and reclamation in extremely heavy saline soil of coastal areas. PMID- 29797904 TI - [Using sequential indicator simulation method to define risk areas of soil heavy metals in farmland.] AB - The heavy metals in soil have serious impacts on safety, ecological environment and human health due to their toxicity and accumulation. It is necessary to efficiently identify the risk area of heavy metals in farmland soil, which is of important significance for environment protection, pollution warning and farmland risk control. We collected 204 samples and analyzed the contents of seven kinds of heavy metals (Cu, Zn, Pb, Cd, Cr, As, Hg) in Zengcheng District of Guangzhou, China. In order to overcame the problems of the data, including the limitation of abnormal values and skewness distribution and the smooth effect with the traditional kriging methods, we used sequential indicator simulation method (SISIM) to define the spatial distribution of heavy metals, and combined Hakanson index method to identify potential ecological risk area of heavy metals in farmland. The results showed that: (1) Based on the similar accuracy of spatial prediction of soil heavy metals, the SISIM had a better expression of detail rebuild than ordinary kriging in small scale area. Compared to indicator kriging, the SISIM had less error rate (4.9%-17.1%) in uncertainty evaluation of heavy metal risk identification. The SISIM had less smooth effect and was more applicable to simulate the spatial uncertainty assessment of soil heavy metals and risk identification. (2) There was no pollution in Zengcheng's farmland. Moderate potential ecological risk was found in the southern part of study area due to enterprise production, human activities, and river sediments. This study combined the sequential indicator simulation with Hakanson risk index method, and effectively overcame the outlier information loss and smooth effect of traditional kriging method. It provided a new way to identify the soil heavy metal risk area of farmland in uneven sampling. PMID- 29797905 TI - [Influence of land intensive use level on main atmospheric pollutants in the central urban area of Nanchang City, China.] AB - At present, urbanization has gradually changed from denotative expansion to connotative development in China. It is urgently needed for intensive use of land resources and the construction of "compact city". However, intensive land use means less land resources to carry more urban elements, therefore people will become more and more sensitive to environmental pollution, especially atmospheric pollution. It is of great significance to study the influence of intensive land use on atmospheric pollution. Taking the central urban area of Nanchang City as a case, this study simulated the concentration of the six main atmospheric pollutants i.e. PM2.5, PM10, SO2, NO2, CO and O3 by ordinary kriging interpolation firstly. Then, sixteen intensive land use variables, including the volume ratio, building density, population density, were analyzed with the partial least squares regression and path analysis in order to reveal the effects of intensive land use level on the atmospheric pollutants. The results showed that the correlations between intensive land use level and PM2.5, PM10 were the strongest, followed by O3 and NO2, and the weakest correlation was between intensive land use level and SO2, CO. The sequence of the correlation between intensive land use variables and the six main atmospheric pollutants in different sample areas was residential area> education area > business area > industrial area. The more intensive the land use was, it had greater impacts on the atmospheric pollutants. The greatest effect was on PM2.5 and PM10, followed by O3, and the least effect was on NO2. The direct, indirect, and integrated influences of intensive land use on atmospheric pollutants were generally equal. Overall, the direct influence of the intensive land use level was greater than the indirect one, among which the influence of the intensive land use level of the residential area was the strongest, followed by the business area, and the education area least. This study provided a new perspective on studying the influence of intensive land use on atmospheric environment, which would provide some reference to solve the atmospheric problems in compacted city. PMID- 29797906 TI - [Research advance in allelopathy effect and mechanism of terrestrial plants in inhibition of Microcystis aeruginosa.] AB - The inhibition of algae reproduction and control of harmful algal bloom are the primary challenges in the ecological restoration of eutrophicated water. It is urgent to inhibit algae over-reproduction in green and effective ways, one of which is the use of plant allelopathic effect. How-ever, few study focused on allelochemicals of terrestrial plants. Here, we introduced inhibition of Microcystis aeruginosa over-reproduction by allelochemicals from three categories of terrestrial plants, including herbaceous plants (Compositae/Papaveraceae, Liliaceae, Graminaceae), woody plants, and Chinese medicine plants. The classification, separation and identification of alleloche-micals from terrestrial plants that could be used for the inhibition of M. aeruginosa were summarized. Finally, the allelopathic mechanism to inhibit M. aeruginosa was discussed in detail to support the development of algistat. We also proposed some suggestions for the further development of algistat. PMID- 29797907 TI - [Clinical observation of "Tongdu Tiaoshen needles therapy" in treating acute cerebral infarction and its effect on autophagy]. AB - OBJECTIVE: To observe the difference of clinical efficacy between "Tongdu Tiaoshen needles therapy" and conventional acupuncture in patients with acute cerebral infarction (ACI) and its relationship with autophagy. METHODS: Sixty patients with ACI were randomly divided into an observation group (30 cases and 2 dropping) and a control group (30 cases and 3 dropping). Conventional drugs were applied in the two groups. In the observation group, acupuncture was applied at Dazhui (GV 14), Fengchi (GB 20), Qiangjian (GV 18), Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Shuigou (GV 26), Quchi (LI 11, affected side), Hegu (LI 4, affected side), Zusanli (ST 36, affected side), and EA was connected at Baihui (GV 20) and Yintang (GV 29). After 30 min, the EA and non-governor vessel acupoints were removed, and the governor vessel points were continued for 20 min. Twirling was used twice every 5 min, 1 min a time. In the control group, acupuncture was applied at Baihui (GV 20), Yintang (GV 29), Quchi (LI 11, affected side), Waiguan (TE 5, affected side), Shousanli (LI 10, affected side), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6, affected side), Taixi (KI 3, affected side), Taichong (LR 3, affected side). EA was connected at Zusanli (ST 36) and Hegu (LI 4). The treatment was given for 10 days, once every day with needle retained for 30 min. National Institute of Health stroke scale (NIHSS), mini-mental state examination (MMSE), modified Barthel index (MBI) scores were observed before and after treatment in the two groups. The clinical efficacy, the changes of contents of LC3-II and Beclin1 in peripheral serum were judged. RESULTS: After treatment, NIHSS score was lower than that before treatment, and MMSE score and MBI score were higher than those before treatment (all P<0.01), and the result in the observation group was better than that in the control group (all P<0.05). Contents of LC3-II and Beclin1 in peripheral serum were higher than those before treatment in the two groups (both P<0.01), and the result in the observation group was better than that in the control group (both P<0.05). The total effective rate in the observation group was 92.9% (26/28), which was better than 70.4% (19/27) in the control group (both P<0.05). CONCLUSION: "Tiaoshen Tongdu needles therapy" have better effect to relieve the clinical symptoms of patients with acute cerebral infarction than conventional acupuncture, which may be related to the increasing number of autophagic bodies and autophagy activity. PMID- 29797908 TI - ["Governor vessel daoqi method of acupuncture" combined with estazolam for insomnia: a randomized controlled trial]. AB - OBJECTIVE: To compare the clinical efficacy differences between "governor vessel daoqi method of acupuncture" combined with estazolam and estazolam alone for insomnia. METHODS: Seventy patients of insomnia were randomly divided into an observation group and a control group, 35 cases in each one. The patients in the control group were treated with oral administration of estazolam, 2 mg each time; the estazolam was taken 30 min before sleeping. The patients in the observation group were treated with "governor vessel daoqi method of acupuncture" combined with estazolam; the positive reaction points along governor vessel and Baihui (GV 20) were selected as the main points. The acupuncture was given for 30 min per treatment, once every two days. Both groups were treated for four weeks. Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were observed before and after treatment. Clinical efficacy was assessed between the two groups and adverse reactions were recorded. RESULTS: The total effective rate was 94.3% (33/35) in the observation group, which had no significant difference with 82.9% (29/35) in the control group (P>0.05). The cured and markedly effective rate was 71.4% (25/35) in the observation group, which was superior to 42.9% (15/35) in the control group (P<0.05). Each item score and total score of PSQI were decreased obviously after treatment in the observation group (all P<0.05), while the score of sleep latency, sleep duration and sleep efficiency as well as total score of PSQI were decreased obviously after treatment in the control group (all P<0.05). The scores of sleep duration, sleep disturbance and day dysfunction due to sleepiness as well as total score of PSQI in the observation group were lower than that in the control group (all P<0.05). After treatment, the PSG-related parameters of total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency were improved significantly in the observation group (all P<0.05); the total sleeping duration, sleeping arousal and sleeping efficiency were also improved in the control group (all P<0.05). The total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency in the observation group were superior to those in the control group (all P<0.05). 4 adverse reactions in the observation group and 3 adverse reactions in the control group were observed. CONCLUSION: "Governor vessel daoqi method of acupuncture" combined with estazolam could significantly improve insomnia, which are superior to estazolam alone. PMID- 29797909 TI - [Acupuncture at back-shu points of five zang, Geshu (BL 17) and Shenmen (HT 7) for the treatment of menopausal insomnia]. AB - OBJECTIVE: To compare the clinical efficacy differences between acupuncture at back-shu points of five zang, Geshu (BL 17), Shenmen (HT 7) and regular medication for the treatment of menopausal insomnia. METHODS: A total of 128 female patients of menopausal insomnia were randomly divided into an observation group and a control group, 64 cases in each one. Four patients in the observation group and 2 patients in the control group dropped out during the treatment. The patients in the observation group were treated with acupuncture at Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Shenmen (HT 7), once a day, and there was an interval of 2 days between every 5 days of treatment. The patients in the control group were treated with oral administration of alprazolam (0.4 mg or 0.8 mg) before sleep. Three-week treatment was taken as one course, and totally three courses were given in the two groups. Pittsburgh sleep quality index (PSQI), levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were observed before treatment and 30 days after treatment; the efficacy was evaluated 30 days after treatment. RESULTS: Each item score and total score of PSQI 30 days after treatment were lower than those before treatment in the two groups (all P<0.05), the scores in the observation group were lower than those in the control group (all P<0.05). The levels of E2 30 days after treatment were higher than those before treatment in the two groups (both P<0.05), but the level of FSH and LH 30 days after treatment were lower than those before treatment in the two groups; the level in the observation group was superior to that in the control group (all P<0.05). The total effective rate was 98.3% (59/60) in the observation group, which was better than 95.2% (59/62) in the control group (P<0.05). CONCLUSION: Acupuncture at Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Geshu (BL 17), and Shenmen (HT 7) has better efficacy for menopausal insomnia than alprazolam. PMID- 29797910 TI - [Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9)]. AB - OBJECTIVE: To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinII(UII) in the patients. METHODS: A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UII. The clinical therapeutic effects were compared among the groups. RESULTS: After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all P<0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all P<0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all P<0.01). After treatment, ESCV scores were all increased remarkably in every group (all P<0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (P<0.05, P<0.01). After treatment, the concentrations of plasma NPY and UII were all reduced remarkably in every group (all P<0.01) and the differences were significant among the groups (all P<0.01). CONCLUSION: The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9). PMID- 29797911 TI - [Acupuncture combined with western medicine on rheumatoid arthritis and effects on blood stasis]. AB - OBJECTIVE: To observe the clinical efficacy of acupuncture combined with western medicine in the treatment of rheumatoid arthritis (RA) and its effect on blood stasis, and to explore ways to improve the clinical curative effect. METHODS: A total of 56 patients of RA were randomly divided into an observation group and a control group, 28 cases in each one. 1 ibuprofen sustained-release tablets, 2 times a day, each time 0.3 g; 2 methotrexate tablets (MTX), once a week, each time 10 mg 3 folic acid tablets, once a week, each time 5 mg were given in the control group, 30 days as one course, a total of 3 courses were required. In the observation group, acupuncture was adopted on the basis of the treatment as the control group. The main acupoints were Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) combined with local ashi points. The treatment was given once every day for continuous 6 days a week, the treatment for 30 days as one course, a total of 3 courses were required. The serological indexs were evaluated before and after treatment, including the rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedirnentation rate (ESR), platelet (PLT), fibrinogen (FBG) and D-dimer (D-D), the changes of disease activity score (DAS-28), symptom grade quantitative score, blood stasis syndrome symptom (the joint tingling, lip color, tongue, pulse, subcutaneous ecchymosis, squamous and dry skin) score were observed. RESULTS: 1 The scores of RF, hs-CRP, ESR, PLT, D-D, FBG, DAS-28 and symptom grade quantitative were significantly improved in the two groups compared with those before treatment (all P<0.05), and the scores of hs-CRP, ESR, DAS-28 and symptom grading in the observation group were more better than those in the control group (all P<0.05). 2 The total score of joint tingling, lip color, tongue, pulse, subcutaneous ecchymosis, squamous and dry skin and blood stasis syndrome in both groups were decreased after treatment (all P<0.05), the joint tingling, tongue, lip color and subcutaneous ecchymosis were improved obviously in the observation group than those in the control group (all P<0.05). 3 The total effective rate in the observation group was 85.7% (24/28), which was better than 75.0% (21/28) in the control group (P<0.05). CONCLUSION: Acupuncture combined with western medicine can not only improve the clinical efficacy of RA patients but also improve the blood stasis. PMID- 29797912 TI - [The effect of "paraplegic triple needling" combined with rehabilitation training on psychological and daily living ability of patients with spinal cord injury]. AB - OBJECTIVE: To compare the effects of "paraplegic triple needling" and conventional needling on psychological and daily living ability of patients with spinal cord injury. METHODS: A total of 50 patients with spinal cord injury were randomized into an observation group and a control group, 25 cases in each one. Rehabilitation training was applied in the two groups. In the observation group, on the basis of rehabilitation training, "paraplegic triple needling" was added, namely, puncturing the governor vessel (GV) and back-shu points respectively in the upper and lower segments of the injury plane and locating the key muscle movement points of the lower extremities by the peripheral nerve electrical stimulation device. Electroacupuncture (EA) was given at the points up and down the two sections of the GV points, back-shu points, the key muscle movement points. In the control group, conventional needling was applied at the points of GV, back-shu points, Huantiao (GB 30), Zusanli (ST 36), Xuanzhong (GB 39) and Yanglingquan (GB 34). The treatment was given once a day, the treatment for a month as one course and a total of 2 course were required. In addition, 25 health checkers were selected at the physical examination center of General Hospital of Chengdu Military Region as a normal control group. The content of peripheral serum 5-hydroxy tryptamine (5-HT) was tested before treatment, 1 course and 2 courses of treatment, The modified Barthel index (MBI) was used to observe the daily living activities, the Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were used to evaluate the psychological status. RESULTS: In the two groups, the content of serum 5-HT was lower than that in the normal control group before treatment (both P<0.05). After one course of treatment, the MBI score and content of serum 5-HT were all increase in the two groups; the HAMA score and HAMD score were all reduced (all P<0.05); the results in the observation were better than those in the control group (all P<0.05). After 2 courses of treatment, the MBI score and content of serum 5-HT were all increased in the two groups, and the HAMA score and HAMD score were all reduced (all P<0.05), but the difference was not significant statistically between the two groups (all P>0.05). Pearson correlation analysis showed that the content of serum 5-HT in patients with spinal cord injury was negatively correlated with disease course, HAMA and HAMD score (all P<0.05), and positively correlated with MBI score (P<0.05). CONCLUSION: There are differences in the content of serum 5 HT between the normal person and the patients with pinal cord injury. The content of serum 5-HT can early predict the depression and anxiety in patients with spinal cord injury. Compared with the conventional needling, "paraplegic triple needling" can improve depression and anxiety in the early stage and improve the daily living ability of patients with spinal cord injury. PMID- 29797913 TI - [Early acupuncture for traumatic intracerebral hematoma: a randomized controlled trial]. AB - OBJECTIVE: To observe the effect of early acupuncture intervention on brain edema in patients with traumatic intracerebral hematoma and explore its mechanism on the basis of conventional western medicine. METHODS: With stratified block randomization, sixty-four patients with glasgow coma scale (GCS) of 6 to 12 were divided into an acupuncture combined with medicine group (a combination group) and a western medication group, 32 cases in each one. In the western medication group, dehydration to reduce intracranial pressure and nutritional nerves were given as the basic treatment. In the combination group, on the basis of the treatment as the western medication group, acupuncture was applied at Xuehai (SP 10), Taixi (KI 3), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), etc. The treatment was given once every day, for 6 times as one course; there was an interval of 1 day between two courses; a total of 4 courses were required. GCS score and recovery time were recored before treatment and on the 7 th, 14 th and 28 th days. 90 days follow-up after treatment, the GOS was observed, and the mortality and effective survival rate were calculated. The Barthel index (BI) score was evaluated before treatment and on the 14th, 21st, 28th days and 90 days follow-up after treatment. Before treatment and 3rd, 7th, 14th, 21st, 28th days, cranial CT or MR scan was performed to calculate the brain edema index (BEI); Plasma interleukin-6 (6IL-6), neuropeptide Y (NPY) and nitric oxide (NO) were measured before treatment and on the 3rd, 7th and 14th days after treatment. RESULTS: (1) The GCS scores increased gradually in the two groups during treatment, and there was significant difference between the 28th days and before treatment (both P<0.05). There were no significant difference between the two groups about GCS score and average recovery time on the 28th days treatment (all P>0.05). (2) The mortality rate of the combination group was 6.3% (2/32) on 90 days follow-up, 9.4% (3/32) in the western medication group (P>0.05). The effective survival rate was 81.3% (26/32) in the combination group, which was higher than 59.4% (19/32) in the western medication group (P<0.05). (3) The BI score was significantly higher than that before treatment on the 28th days and 90 days follow-up in the two groups (all P<0.05), and the result in the combination group was superior to that in the western medication group (both P <0.05). (4) The BEI decreased on the 14th, 21st and 28th days in the two groups (all P<0.05), and on the 14th day, the BEI decreased more significantly in the combination group than that in the western medication group (P<0.05). (5) The levels of IL-6, NPY and NO decreased on the 7th and 14th days in the two groups (all P<0.05), and decreased more significantly in the combination group than that in the western medication group on the 7th day (P<0.05). CONCLUSION: On the basis of conventional western medicine, early acupuncture can reduce cerebral edema and improve the prognosis of patients, and acupuncture combined with medicine are superior to western medicine alone. Acupuncture mechanism may be related to reducing the expression of inflammatory response. PMID- 29797914 TI - [Catgut implantation at stellate ganglion for postmenopausal osteoporosis]. AB - OBJECTIVE: To compare the efficacy differences between catgut implantation at stellate ganglion combined with oral administration of alendronate sodium and oral administration of alendronate sodium alone on postmenopausal osteoporosis (PO). METHODS: Sixty patients of PO were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with oral administration of alendronate sodium. Based on the treatment of control group, the patients in the observation group were treated with catgut implantation at stellate ganglion. The treatment was given once a week in the two groups; the consecution treatment of four weeks constituted one session, and totally six sessions were given. The changes of total syndrome score, bone mineral density of lumbar vertebra (L1 to L4) and femeral neck (FN) and estradiol were observed before and after treatment; the clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the total syndrome score, bone mineral density of lumbar vertebra (L1 to L4) and FN and estradiol were significantly improved after treatment (all P<0.05); which were more significant in the observation group (all P<0.05). Compared before treatment, the level of estradiol in the control group was not significantly changed after treatment (P>0.05), while that in the observation group was significantly changed after treatment (P<0.05). After treatment, the level of estradiol in the observation group was higher than that in the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, which was significantly higher than 83.3% (25/30) in the control group (P<0.05). CONCLUSION: Catgut implantation at stellate ganglion combined with oral administration of alendronate sodium are superior to oral administration of alendronate sodium alone for postmenopausal osteoporosis, which improve the clinical symptoms, regulate the hormone level and increase bone mineral density. PMID- 29797915 TI - [Theoretic exploration and clinical application of acupoint combination based on biaoben theory]. AB - In the guidance of preventive treatment, taking "consolidation and non obstruction" as the core, emphasizing the importance of the antipathogenic qi in the treatment, the method of "biaoben acupoint combination" was proposed in acupuncture therapy. In the paper, the theoretic basis and the connotation of "biaoben acupoint combination", the application of the key acupoint combination and the study on cardiovascular system, digestive system and immune system were introduced and it was anticipated to provide the theoretic evidences for the acupoint selection and enrich the contents of acupoint combination in acupuncture. PMID- 29797916 TI - [Standardization on the location of Fengshi (GB 31)]. AB - OBJECTIVE: To compare the difference in the manual measurement of Fengshi (GB 31) between the standing position and the supine position so as to determine the location. METHODS: A total of 197 volunteers were included in the manual measurement of Fengshi (GB 31) at the standing position and 92 volunteers at the supine position. The differences were compared between the two measurements. RESULTS: The results in the manual measurement at the standing position showed that the distance was (39.27+/-3.83) cm from the greater trochanter of femur to the popliteal transverse crease [(39.96+/-4.21) cm in males, (38.82+/-3.49) cm in females, P < 0.05]. The distance was (19.08+/-2.97) cm from the tip of the middle finger to the popliteal transverse crease [(18.96+/-3.50) cm in males, (19.16+/ 2.58) cm in females]. After calculating according to the formula of proportional bone measurement, Fengshi (GB 31) was located (9.28+/-1.44) cun above the popliteal transverse crease [(9.07+/-1.64) cun in males, (9.42+/-1.29) cun in females]. The results in the manual measurement at the supine position showed that the distance was (41.89+/-3.88) cm from the greater trochanter of femur to the popliteal transverse crease [(42.36+/-3.88) cm in males, (41.67+/-3.89) cm in females]. The distance was (23.01+/-3.37) cm from the tip of the middle finger to the popliteal transverse crease [(22.50+/-3.73) cm in males, (23.25+/-3.20) cm in females]. After calculated according to the formula of proportional bone measurement, Fengshi (GB 31) was located (10.51+/-1.69) cun above the popliteal transverse crease [(10.16+/-1.75) cun in males, (10.67+/-1.63) cun in females]. CONCLUSION: Fengshi (GB 31) is located on the femoral region, in the depression under the tip of the middle finger at the standing position. The simple localization of the acupoint at the supine position: at the supine, the palm touches the middle of the lateral side of the thigh, about 1 cun directly below the depression under the tip of the middle finger. The location of Fengshi (GB 31) in female is slightly upper than male. PMID- 29797917 TI - [Effects of electroacupuncture on inflammatory response of cardiac muscle tissue in mice with acute myocardial ischemia]. AB - OBJECTIVE: To observe the effects of electroacupuncture (EA) on inflammatory reaction of acute myocardial ischemia (MI) in mice, and to explore its action mechanism. METHODS: Forty adult male C57BL/6 mice were randomly divided into a control group, a sham operation group, a model group and an EA group, 10 mice in each one. The model was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 mA of intensity and 2 Hz /100 Hz of frequency; EA was given 30 min per treatment, once a day for totally 5 days. The mice in the control group and model group were treated with immobilization and no EA was given. The mice in the sham operation group were not treated with ligating at the left anterior descending branch of coronary artery, but the remaining procedure was identical to the model group. The electrocardiogram was recorded and ?ST was calculated to evaluate the model. TTC and HE staining methods were applied to evaluate the infarct size and pathologic change of myocardial tissue, respectively. Western blot method was applied to test the protein expression levels of tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB p65 (NF-kappaB p65), interleukin-1beta (IL-1beta) and interleukin-8 (IL-8). RESULTS: Compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously after modeling (both P<0.01), indicating the MI model was established successfully. The TTC and HE staining results indicated, compared with the sham operation group, the model group had larger infarction size (P<0.01), more myocardial fibers injury and inflammatory infiltration; compared with the model group, the infarction size of the EA group was significantly reduced (P<0.01), and the myocardial fibers injury and inflammatory infiltration were improved. Compared with the control group, the protein expression levels in the sham operation group were similar (all P>0.05); compared with the sham operation group, the expression levels of TNF-alpha, NF kappaB p65, IL-1beta and IL-8 were significantly increased in the model group (P<0.01, P<0.05); compared with the model group, the expression levels of TNF alpha, NF-kappaB p65, IL-1beta and IL-8 were significantly reduced in the EA group (all P<0.05). CONCLUSION: EA might reduce the protein expression levels of TNF-alpha, NF-kappaB p65, IL-1beta and IL-8 in cardiac muscle tissue to inhibit inflammatory reaction and achieve myocardial protective effect in mice with acute myocardial ischemia. PMID- 29797918 TI - [Effects of electroacupuncture at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency]. AB - OBJECTIVE: To explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI). METHODS: A total of 48 SD female rats with regular estrus were divided into a blank group (n=8), a model group (n=10), an EA group (n=10), a binding group (n=10) and a tamoxifen (TAM) group (n=10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet. After the model was established successfully, the rats in the EA group were treated with EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) with continuous wave (1 to 3 Hz, 0.1 to 1 mA) for 20 minutes, once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the TAM group were treated with subcutaneous injection of tamoxifen (1mg/kg), once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the binding group were bound by a small sack as the EA group. The rats in the blank group and the model group were treated with normal diet. After four weeks, the sexual gland weight and index were tested in each group; the ELISA method was applied to test the level of anti-mllerian hormone (AMH) and inhibin B; the morphology of ovary was observed; the number of primordial follicles, primary follicle, antral follicle and atretic follicle was counted; the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) were measured. RESULTS: (1) Compared with the blank group, the ovary weight, ovary index, uterus weight and uterus index were significantly decreased after treatment in the model group, EA group, binding group and TAM group (all P<0.01); but the differences between the model group and the EA group, binding group, TAM group were not significant (all P>0.05). (2) Compared with the blank group, the levels of serum AMH, inhibin B and E2 were significantly reduced; the levels of FSH and LH were significantly increased in the model group; EA group, binding group and TAM group (all P<0.01). Compared with the model group, the levels of serum AMH, inhibin B and E2 were significantly increased, the level of FSH and LH were significantly reduced in the EA group and TAM group (all P<0.01). (3) Compared with the blank group, in the model group, EA group, binding group and TAM group the ovary was dark red and pale, surrounded by particle or not; the morphology was small and atrophic; the primordial follicles was reduced even vanished; the structure of primary follicle was damaged and loosely arranged; the mature follicle was few; the atretic follicle and interstitial gland were increased. (4) Compared with the blank group, the expressions of IGF-1 mRNA and IGF-1R mRNA were increased in the model group (all P<0.01); compared with the blank group, the expression of IGF-1 mRNA was increased in the binding group (P<0.05), but that of IGF-1R mRNA was not significantly different (P>0.05); compared with the model group, the expression of IGF-1 mRNA was not significantly different in the EA group, binding group and TAM group (all P>0.05), but that of IGF-1R mRNA was reduced (P<0.05, P<0.01). CONCLUSION: EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) has improvement effect on ovarian function in rats with VCD-induced POI, which is likely to be related to regulating the IGF-1R mRNA expression to improve the IGF-1/ IGF-1R axis. PMID- 29797919 TI - [Acupoint selection for acupuncture analgesia based on the relationship of "the opening-closing- pivoting theory" with meridians and zangfu organs]. AB - "The opening-closing-pivoting theory" recorded in Neijing (Internal Classic) visualizes the qi activity of six meridians and indicates the relationship among the six meridians in physiology and pathology. Through the analysis on the classic medical works and modern literature of TCM by the modern medical masters, a specific relationship is discovered among the hand and foot meridians of the same name and among the zangfu organs. The qi is corresponded and interacted among the hand and foot meridians of the same name. Except the exterior and interior relationship among the zangfu organs, the related communication is also existing. Both meridians and zangfu organs are closely related to "the opening closing- pivoting" theory. This discovery is the inheritance and development of "the opening-closing-pivoting theory" and plays the important role in the guidance of the acupoint selection of clinical acupuncture analgesia. PMID- 29797920 TI - [Literature analysis on moxibustion at Yongquan (KI 1) for insomnia]. AB - OBJECTIVE: To summarize and analyze the clinical literature regarding moxibustion at Yongquan (KI 1) for insomnia, and to provide clinical evidence of moxibustion at Yongquan (KI 1) for insomnia. METHODS: With "moxibustion" "acupuncture moxibustion" "Yongquan (KI 1)" "insomnia" and "sleep disorder", etc. as key terms, the clinical literature regarding moxibustion at Yongquan (KI 1) for insomnia was retrieved in CNKI, Wanfang and VIP databases, and reviewed, summarized and analyzed. RESULTS: A total of 27 clinical papers were retrieved, including 14 randomized controlled trials. In recent years, the number of clinical papers had increased. Few papers selected moxibustion at Yongquan (KI 1) as independent treatment for insomnia; most papers combined moxibustion with acupuncture, massage, etc. Moxibustion was commonly manipulated by patients or family members, and few papers applied moxibustion instruments to make the manipulation easier and safer. CONCLUSION: Moxibustion at Yongquan (KI 1) for insomnia has attracted more and more attention. It is suggested to apply convenient and safe moxibustion instruments in clinical treatment, which is benefit to clinical generalization, but also provides convenient manipulation for further study regarding its clinical effect and mechanism. PMID- 29797921 TI - [Contribution of Jiusheng by ZHOU Meisheng to moxibustion]. AB - Mr. ZHOU Meisheng was a famous acupuncturist in China. He succeeded the acupuncture from his family in childhood, and practiced acupuncture strictly with insightful and original perspective. The Jiusheng, one of his magnum opus, proposed innovative ideas in the theory and clinical practice of moxibustion, such as revival of moxibustion, three phases of moxibustion sensation, moxibustion for heat syndromes. In this article, the contribution of Jiusheng to moxibustion was discussed from background of compiling this book, poem and medical cases, explanation on moxibustion theory and practice and its effects on later ages. PMID- 29797922 TI - [A study of acupuncture under the perspective of international discourse power: based on metrological analysis of Web of Science core collection in the last 10 years]. AB - In order to reflect the research achievements of acupuncture on international academic community and study the acupuncture international discourse power from 2007 through 2017, we used text analysis software to analyze 5668 papers that focusing on acupuncture research in the recent 10 years. The results show that international acupuncture research trend has been formed, the research force diverges to the rest of the world with "China-America" as the center, and the study focuses on its sight and the interaction between China and foreign countries is good. Under the perspective of international discourse power, the construction of the national communication platform, the cultivation of academic centers and research fields, and the interaction with international research forces will enhance the quality of Chinese acupuncture research, and these will become an important task in enhancing the international discourse power of Chinese acupuncture. PMID- 29797923 TI - [Clinical research and the effect mechanism on premature ovarian failure treated with acupuncture in recent 20 years]. AB - OBJECTIVE: To review and collect the study achievements and the effect mechanism of acupuncture in the treatment of premature ovarian failure (POF) in recent 20 years so as to provide more references for the clinical treatment of POF with acupuncture. METHODS: Through retrieving PubMed, CNKI and VIP, the literature on acupuncture for POF was collected from January 1, 1998 through March 31, 2017 regarding the rule of acupoint selection and the therapeutic method. The potential effect mechanism was explored. RESULTS: Finally, 26 papers on the clinical treatment for POF with acupuncture and 5 ones on the laboratory mechanism were obtained. The differentiated syndromes and the top 3 acupoints for the treatment of POF included shaoyin syndrome [Taixi (KI 3), Sanyinjiao (SP 6) and Guanyuan (CV 4)], Taiyin syndrome [Sanyinjiao (SP 6), Zusanli (ST 36) and Ciliao (BL 32)], jueyin syndrome [Taichong (LR 3), Shenting (GV 24), Guanyuan (CV 4)], the mixed syndrome of shaoyin and jueyin [Sanyinjiao (SP 6), Ganshu (BL 18) and Shenshu (BL 23)], the mixed syndrome of shaoyin and taiyin [Pishu (BL 20), Sanyinjiao (SP 6) and Zusanli (ST 36)] and the dysfunction of the thoroughfare vessel and the conception vessel [Guanyuan (CV 4), Zigong (EX-CA 1) and Huangshu (KI 16)]. The top 5 acupoints of the 14 meridians were Guanyuan (CV 4), Shenshu (BL 23), Sanyinjiao (SP 6), Zhongji (CV 3), Pishu (BL 20), Taixi (KI 3) and Ganshu (BL 18). The local extraordinary points were dominant. According to the use frequency of the acupoints, the first top 5 meridians were the bladder meridian of foot-taiyang, the governor vessel, the conception vessel, the spleen meridian of foot-taiyin and the kidney meridian of foot-shaoyin. The most acupoints were distributed in the chest, the abdomen, the lumber region and the lower limbs. Many therapeutic methods were used, such as acupuncture with filiform needle, electroacupuncture, moxibustion and the acupoint thread embedding therapy. The effect mechanisms possibly referred to the recovery of the sexual level through regulating the hypothalamus-pituitary gland-ovarian axle (HPOA) function, the improvement of the histological morphology of the uterine, the improvement of body immunity through affecting the nerve-endocrine-immune regulation system as well as the regulation of the genetic and protein expressions of the signal pathway relevant with POF. CONCLUSION: Even though acupuncture has achieved the therapeutic effects in the clinical treatment of POF, the research on the effect mechanism is still limited. The exploration of acupuncture for POF in terms of mechanism may guide the clinical practice. In the future study, the clinical pathway should be specified and the effect mechanism be explored through the rigorous laboratory design and more objective and rational evaluation system. PMID- 29797924 TI - [The clinical application of coblation in diseases of nasal cavity]. PMID- 29797925 TI - [The clinical application of coblation in laryngopharyngeal,head and neck surgery]. PMID- 29797926 TI - [The application of coblation in surgical treatment of patients with obstructive sleep apnea hypopnea syndrome]. PMID- 29797927 TI - [The application of radiofrequency ablation in the resection of lateral skull base tumor through an endoscopic endonasal approach]. AB - Objective:To summarize our experience of resecting tumors in lateral skull base via a radiofrequency ablation-assisted endoscopic approach to investigate the safety and feasibility of the technique and to assess its treatment outcomes.Method:Twelve patients with lateral skull base tumor were operated through a radiofrequency ablation?assisted endoscopic transnasal or transoral approach. In this study, the operative technique was described,and the degree of resection, complications and the clinical outcomes was analyzed.Result:Complete resection was achieved in all patients using this technique. No patient in the series experienced a new neurological deficit, cerebrospinal fluid leak or meningitis after surgery. One patient suffered from dissecting aneurysm on 4th day after operation. And the dissecting aneurysm were treated by vascular interventional therapy. No recurrence and death related skull base tumor in the follow-up period(28-30 months) were found. The volume of intraoperative blood loss was from 60 ml to 500 ml(medium 190 ml). The duration of operations was from 60 min to 180 min(medium 95 min).Conclusion:Our limited experience indicates that this technique is feasible and safe for the complete resection of some skull base tumors in selected cases. PMID- 29797928 TI - [The comparative analysis of hypothermia plasma ablation and conventional resection method in endoscopic transnasal surgery for squamous-cell carcinoma in pterygopalatine fossa]. AB - Objective:To comparative analyze the difference of effect between hypothermia plasma ablation and conventional resection method in endoscopic transnasal surgery for squamous?cell carcinoma in pterygopalatine fossa.Method:Retrospectively analyzed clinical data of 38 patients with maxillary sinus squamous-cell carcinoma invading pterygopalatine fossa admitted and treated with endoscopic surgery by department of otorhinolaryngology head and neck surgery of Chinese PLA general hospital. The patients were divided into two groups (hypothermia plasma ablation group and conventional resection group) according to different methods of resection. Compare the mean operating time, the amount of bleeding, the hospitalization days, the rate of surgery complications and the healing time between two groups.Result:Patients in both groups underwent total resection, compare the hypothermia plasma ablation group and conventional resection group, the mean operating time was(244.00+/-62.86)min and(294.17+/ 73.49) min,respectively(P <0.05);the mean amount of bleeding was (481.50+/ 426.43)ml and(790.00+/-387.34)ml,respectively(P <0.05);the rate of surgery complications was 0 and 11%,respectively(P >0.05); the mean hospitalization days was(16.75+/-4.45)d and (19.89+/-4.84)d,respectively(P <0.05); the mean healing time was (8.35+/-1.31) w and(9.61+/-2.20)w,respectively(P <0.05);the 3 years recurrence rate was 34.3% and 49.4%,respectively(P >0.05). Conclusion:All the patients in the study achieved relatively complete resection of tumor,the hypothermia plasma ablation has the advantage in terms of resection efficiency,the control of bleeding and the time of postoperative recovery. The feature of safe and minimally invasive has made it an important aid in skull base surgery. PMID- 29797929 TI - [Clinical effect analysis of adenoidectomy and tonsillectomy assisted with ablation on children]. AB - Objective:This study aims to explore the clinical effect of adenoidectomy and tonsillectomy assisted with ablation on children.Method:The investigation took the form of retrospective review of 2 089 cases of children applied with adenoidectomy and tonsillectomy assisted with ablation in our hospital in recent 10 years. We obtained data of these children with epidemiological methods based on analyzing the status of general information and operation selections, and then analyzing the scores of snoring and breath preoperation and postoperation.Result:1General information of 2 089 cases followed with: the ratio of male and female was 2.08?1,the average onset age was(5.87+/-3.12)years old, mostly ranged from 3 to 7 years old, which consists of 76.35%(1595/2089)of the group.2Different surgery methods of tonsil consisted of three groups as: partial resection associate with ablation was 69.17%(1445/2089), ablation alone was 22.26%(465/2089) and partial resection alone was 8.57%(179/2089) of the group.3A high level scores of snoring and breath more frequently found in preoperative cases than in postoperative cases(P <0.01).There are no differentiation among the scores of above three groups(P >0.05).The postoperative effect evaluation were related to allergic rhinitis, recurrent of tonsillitis, obesity, circular occipital hyperplasia and nasopharyngeal adhesion.Conclusion:The results suggested that surgery assisted with ablation has its advantage in adenoidectomy and tonsillectomy. Individual therapy for different children will improve the curative effect and relieve the pain of operation, thus is worth a wide application. PMID- 29797930 TI - [Application of CT angiography for detecting perforator vessels in the anterolateral thigh flap surgery]. AB - Objective:To investigate the effectiveness of CT angiography for detecting perforator vessels in the anterolateral thigh flap surgery.Method:Eight patients with oral and maxillofacial soft tissue defects were repaired with the anterolateral thigh flap. Preoperative CT angiography was conducted to detect perforator vessels. The perforator vessel with large diameter, abundant blood flow, and long pedicle was selected to design the flap.Result:The position of perforator vessels during operation were completely consistent with those detected by CT angiography. The anterolateral thigh flap for 8 cases tally survived.One case had the vascular crisis,which was survived after surgical exploration. The flap ranged from 10 cm*5 cm to 6 cm*4 cm in size. Donor recipient site was not severe complications.Conclusion: CT angiography can be used to locate the perforator vessels preoperatively and accurately,which is beneficial for surgeons to design the flap and reduce surgical complications. The anterolateral thigh flap is an effective method of repairing oral and maxillofacial soft tissue defects. PMID- 29797931 TI - [The experience of abundant amount of pectoralis major myocutaneous flap tissue in restoring parenchyma defect of head and neck]. AB - Objective:Explore the skills to flap the defects of the head and neck with myocutaneous of pectoralis major which has rich amount of organization to minimize complications.Method:Various of neck defects will be repaired when the myocutaneous flap of pectoralis major from obese male or/and female has been prepared with improved methods. First of all, the muscle must be fixed. Then we have to suture the skin and the defect of skin or mucous membrane;the potential closed cavities around the myocutaneous flap must be drainaged with the negative pressure after repaired. Clinical data of 23 (24 sides) patients undergoing the repair in our hospital between January 2008 and December 2014 were collected and reviewed retrospectively.Result:One of 23 cases was injured the thoracoacromial artery in the preparation process of myocutaneous flap by the operator, then we operated on the other side. All of the pectoralis major myocutaneous flaps has been survived except 1 case which was necrosis in distal partial of pectoralis major muscle flap, but healed after changing dressing.Three cases with pharyngeal leakage because of the infection were also healed after changing dressing; skin and skin flap partial dehiscence happend in 1 cases, but also healed after dressing; 1 cases with subcutaneous hemorrhage was healed after cleaning up hematocele.Conclusion:The pectoralis major myocutaneous flap is still a good material for the repair of head and neck defects as long as the management skill in perioperative has been mastered properly, even though the one with rich amount of organization is bloated and the preparation and repair is difficult. PMID- 29797932 TI - [Clinical application of iodine solution staining in the diagnosis of early laryngeal cancer with electronic endoscope]. AB - Objective:To discuss the feasibility and clinical application value of the laryngeal iodine staining under the electronic fiber laryngoscope.Method:Will meet the inclusion criteria of 90 patients, randomly divided into three groups, set to a, b, c group.a ,all patients in the a group were examined by electronic fiber mirror, NBI mode and 0.5% Lugol liquid iodine staining method in three ways. b, all patients in the b group were examined by electronic fiber mirror, NBI mode and 1.0% Lugol liquid iodine staining method in three ways. c,all patients in the c group were examined by electronic fiber mirror, NBI mode and 1.5% Lugol liquid iodine staining method in three ways. The location and range of positive lesions were recorded in each person of the three groups, positive lesions were biopsy, if the positive lesion is repeated, the site can only take a biopsy. As a diagnostic gold standard, the results of the other tests were compared with the results of other tests. And to observe the color of iodine in the throat, all patients were followed up for 24 hours in the presence of dyspnea, severe pain in the throat and other symptoms, and 24 hours after the examination again electronic fiber optic examination. Biopsy was performed in all patients, as gold standard. Using chi square test, inspection standardP <0.05.Result:As the solution of the iodine concentration increased, the rate of the laryngeal was cancer gradually increased. Ninety people take part in the experiment, no one has serious complications. All the patients have no significant inflammation on the mucous membrane of the throat and the subglottic airway afer 24 hours, by the electronic fiber laryngoscope. 1% and the following concentration of Lugol solution for iodine staining, sensitivity to the diagnosis of early laryngeal cancer was higher than that of electronic fiber,the two methods were compared, and the statistical analysis was performed(P >0.05). No statistical significance. There was no significant difference in the diagnosis of early laryngeal cancer. Contrast between iodine stain with 1.5% Lugol solution and electronic fiber sus pension, after statistical calculation(P <0.05);both are statistically significant, and the difference is significant.Comparison of iodine stain with 1.5% Lugol solution and NBI examination, make statistical analysis,P >0.05, there was no significant difference between the both.Conclusion:The 1.5% and below the concentration of the iodine staining under the electronic fiber laryngoscope can be safely applied to inspect the throat, and 1.5% Lugol iodine solution in the diagnosis of laryngeal cancer in the early stage of laryngeal cancer is better than using electronic, and has a certain value in clinical application. PMID- 29797933 TI - [Analysis on the total allergens of phoenix roebelenii pollen with two dimensional electrophoresis followed by immunoblotting]. AB - Objective:To investigate allergen extract and to seek the main allergens of phoenix roebelenii pollen by the technology of two dimensional electrophoresis(2 DE)in protein analysis and immunoblotting.Method:Phoenix roebelenii pollen allergen extract was prepared with routine method, 2-DE combined with immunoblotting assay(Western Blotting),laser imagescanning, 2-DE gel analysis software were used to analyzing its protein components.Result:About 601 soluble proteins spots were revealed in coomassie stained gels.Most of the proteins had a molecular weight (Mr) of 20 to 130 kD, and an isoelectric point(pI) value of 4.0 to ?8.0?. Immunoblotting of 2-DE were showed and there were 19 specific antigen spots, compared with the controls.Conclusion:2-DE is a good method in protein analysis of ephemeroptera allergen extract, and it is useful in seeking main allergens and further research for allergic components. PMID- 29797934 TI - [The function of regulator cAxin2 in inner ear development of chick embry]. AB - Objective:To study the mechanism of the Wnt families'negative regulator cAxin2 in early inner ear development of chick embryo.Method: Plasmid was constructed with enhanced green fluorescent protein(EGFP), cAxin2 and short hairpin RNA(shRNA), which was transfected in otic vesicle by in ovo electroporation. Expression of cAxin2,cPax2(Pared box2),and cBMP4(bone morphogenetic protein 4) genes was investigated in the transfected oticvesicle with situ hybridization.Result:cAxin2 expression was inhibited by shRNA,cPax2 was down regulated and cBMP4 was up regulated as well as an abnormally enlarged otic vesicle was discovered in the transfected otic vesicle. Conclusion:cAxin2 is an important regulatory gene required for inner ear development. PMID- 29797936 TI - [The guiding role of preoperative visual analog scale symptom scores in patients with chronic rhinosinusitis during perioperative period]. AB - Objective:To assess the guiding role of preoperative visual analog scale(VAS) symptom scores in patients with chronic rhinosinusitis(CRS) during perioperative period.Method:The patients with CRS undergoing endoscopic sinus surgery were divided into experimental group and control group according to doctor group.Preoperative VAS symptom scores which including the overall symptom score and every single symptom scores were assessed. Patients with symptom(nasal congestion, nasal discharge, dizziness or headache, hypoamia or anosmia, rhinocnesmus, sneeze) scores more than 5 points were taken corresponding appropriate strategies in experimental group, but conventional empirical measures in control group during perioperative period.Nasal endoscopic surgeries were performed under local or general anesthesia after preoperative preparation. Postoperative follow?up were performed in six months and one year for the overall symptom and each symptom scores in both groups. SPSS?17.0? was used for statistical analysis.Result:There was no statistical difference in general condition, overall symptom score and every symptom scores before operation between experimental group(120 cases) and control group(82 cases) (P >0.05). At the three time points (preoperative, six months, one year after operation), significant differences were found in the two groups about VAS overall symptom score (P <0.05). Except hypoamia, VAS for the other symptoms in different postoperative time showed statistical significance (P <0.05).Conclusion:Preoperative VAS symptom score can be used not only in the evaluation of severity and treatment effect,but also in the guiding of perioperative treatment for CRS, which is worthy of using widely in clinic. PMID- 29797935 TI - [Investigation of CXCR4 mediated chemoresistance in nasopharyngeal carcinoma cell line CNE2]. AB - Objective:Since nasopharyngeal carcinoma is easy to develop resistance during cisplatin-based chemotherapy,CXCR4 expression levels were elevated in mang tumors,and the factor to do with tumor metastasis and chemotherapy drug resistance,and so on has a very important link.We established cisplatin-resistant nasopharyngeal carcinoma cell line, named as CNE2/DDP, and investigated the function of CXCR4 in molecular mechanism behind this resistance.Method:CNE2/DDP was firstly build up by increasing concentration of cisplatin. And then afterwards,MTT assay, RNA interference techniques, microRNA overexpresion techniques, quantative PCR and western blotting were applied to analyze the function of CXCR4 and its downstream effectors.Result:1the expression of CXCR4 was increased in CNE2/DDP and downregulation of CXCR4 with CXCR4 siRNA was able to decrease the resistance of CNE/DDP to cisplatin; 2the expression of let-7a was decrease in CNE2/DDP, while the expression of bcl-2 was increased. Upregulation of let-7a via transfection of let-7a mimics could downregulate the expression of bcl-2 and damage the resistance of CNE2/DDP to cisplation;3downregulation of CXCR4 through CXCR4 siRNA transfection was capable of improving the expression of let-7a. Conclusion:We were the first to found that CXCR4 was related to chemoresistance of CNE2/DPP to cisplatin. Meanwhile, we confirmed that CXCR4 affected the expression of bcl-2 through regulating the expression of let-7a to modulate the chemoresistance of CNE2/DPP to cisplatin. PMID- 29797937 TI - [Relationship among airway infection, lung function damage and the tumor recurrence in patients with laryngeal cancer]. AB - Objective:To investigate the relationship among airway infection, lung function damage and the tumor recurrence in patients with laryngeal cancer.Method:Eighty six patients with laryngeal cancer were retrospectively analyzed.Infection rate were compared between different surgical airway and operation time, the lung function damage and the tumor recurrence were analysed.Result:Total laryngectomy group joint cervix lymph node dissection showed higher airway infection rate than laryngectomy[32.5%(13/40)vs 4.3%(2/46),P <0.05]. Significant differences were observed among operation time<4 h, 4-6 h,>6 h airway infection rate is statistically [2.5%(1/40),19.4%(6/31),53.3%(8/15), P <0.05]; Infection rate was positively correlated with the trachea and the operation time(r=0.41P <0.01). Significant rise in FEV1% and reduce in V25 were observed after operation(P <0.05). No statistical difference were observed in patients with airway infected or uninfected with tumor recurrence and uninfected group is [13.3% (2/15)vs 9.9%(7/71),P > 0.05].Conclusion:Throat cut method may lead to airway infection and impairment of the lung function, but airway infection has no obvious effect in tumor recurrence. PMID- 29797938 TI - [Revised endoscopic sinus surgery combined middle turbinectomy in the treatment of refractory rhinosinusitis]. AB - Objective:To investigate the comprehensive curativeeffect of refractory rhinosinusitis by endoscopic sinus surgery and middle turbinate resection.Method:A retrospective analysis with 178 cases of refractory rhinosinusitis.According to the operation methods, these patients were divided into two groups, observation group and control group, with 89 patients each. The observationgroup received revision endoscopic sinus surgery combined with middle turbinectomy and the control with traditional surgery. Follow?up to observe the curative effect and recurrence rate between the two groups. Result:Follow-up after 6 months, total effective rate of observation group was 88.76% and the effective rate of control group was 68.54%.The total effective rate of observation group is higher than the control group, and non efficiency rate is lower than that of the control group; besides that the incidence of complications and the recurrence rate of the observation group was lower than the control group. Conclusion:It can effectively prevent the recurrence of sinusitis by the revised operation of nasal endoscopic frontal sinus combined with middle turbinate partial or complete removal and fully treatment measures of peri operation period, that is to say it can improve the therapeutic effect of refractory sinusitis witch worthing the clinical popularization and application. PMID- 29797939 TI - [Clinical research on the treatment for benign lesions in maxillary sinus by endoscopic prelacrimal duct recess approach]. AB - Objective:To explore thecomplication and clinical effects of treatment for benign lesions in maxillary sinusby endoscopic prelacrimal duct recess approach. Method:A retrospective analysis of 82 patients with benign lesions in maxillary sinus.Among them there were 37 cases of inverted papilloma,45 cases of maxillary cyst. According to surgical approaches,they were divided into observation group in which 39 cases were treated by combined middle meatus and prelacrimal duct recess approachunder endoscope,contrast group1in which 22 cases were treated by combined middle meatus and inferior meatus approach and contrast group 2 in which 21 cases were treated bycombined middle meatus and Caldwell-Luc approach. Operation time, amount of bleeding during operation, length of hospitalization, postoperative complications and postoperative curative effect,were observed, recorded and compared among the three groups.Result:The 82 patiengs were successfully treated by surgery and followed up of 3 months to 24 months.There were no significant difference between observation group and contrast group1 in operation time, amount of bleeding during operation,length of hospitalization(P >0.05), there were statistical difference in post-operative complicationand recurrence rate(P <0.05).There were statistical difference between observation group and contrast group 2 in operation time, amount of bleeding during operation,length of hospitalization andpost-operative complication(P <0.05),there were no significant difference in recurrence rate(P >0.05).Conclusion:Anterior lacrimal recess with the nasal endoscopyis is useful to the lesions of maxillary sinus anterior wall, anterior lower internal wall, anterior lacrimal recess and alveolar crypt. Theoperation time, bleeding and surgical injuries are less. Patients recover fast with less recurrence. Thus, this method is an idealoperation method to deal with benign diseasesin maxillary sinus. PMID- 29797940 TI - [The clinical application of tinnitus handicap index(THI-12) Chinese version]. AB - Objective:The original prospective of this study is to explore a convenient tinnitus severity assessment tool, using Chinese version of THI-12.Method:We surveyed 229 outpatients on their first hospital visits with primary tinnitus as chief complaint. Both the Chinese version THI-12 and the standard THI-25 were administrated. Their tinnitus grading and administration time were compared. The correlation between the two scores was evaluated. A reliability and factor analysis of the Chinese version of THI-12 was also performed.Result:Two hundred and fifteen of the 229 questionnaires were valid with a 93.9% response rate. The average administration time was(18.9+/-21.0) min for the standard THI-25 and(8.96+/-4.70)min for the Chinese version THI-12, which was significantly different. Pearson's correlation coefficient between the two total scores was r=0.833(P <0.01), which indicates a strong positive correlation.The tinnitus grading was not statistically significant(Z=-0.307,P >0.05).Cronbach's coefficient of THI-12 was alpha=0.765, suggesting good reliability and internal consistency. Factor analysis found three entries with characteristic values greater than 1. These three common factors explained 51.77% of the overall variance, suggesting that the 12 entries can be grouped into three dimensions(emotionality, sociality, concentration). Entry"Because of your tinnitus is it difficult for you to concentrate? "had the highest common value(0.78), suggesting that this entry would contribute the most should all entries be divided into three dimensions.Conclusion:The Chinese version THI-12 is time-efficient, has good reliability and internal structural validity, and provides good assessment of tinnitus severity.It can be widely applied in clinical practice. PMID- 29797941 TI - [Different treatments of maxillary and mandible in management of para-pharynx and cranial base surgery]. PMID- 29797942 TI - [Polyp within massive concha bullosa: a case report]. AB - To discuss the complication of common anatomic variant of the middle turbinate concha bullosa. We present a 63 years old man with nasal obstruction who was diagnosed to be a polyp originated from concha bullosa by CT and operation. Polyp originated from middle meatus was squeezed into concha bullosa. Endoscopic operation is the best treatment to this disesase. Concha bullosa can result in obstruction of middle meatus and then lead to sinusitis. This case, polyp originated from middle meatus was squeezed into concha bullosa, it was a rare occurrence. PMID- 29797943 TI - [Hypopharyngeal angiofibroma: a case report]. AB - Swallowing obstruction, gradually increase, with a sore throat, no fever, no haemoptysis, no dyspnea, routine tests: blood routine, biochemical examination, blood coagulation routine, electrocardiogram, chest X-ray, did not show abnormalities. PMID- 29797944 TI - [Current diagnosis and treatment of pseudoaneurysms of the internal carotid artery in postirradiated nasopharyngeal carcinoma]. AB - Nasopharyngeal carcinoma is one of the most common of head and neck malignant tumors in southern region of China. Till date radiotherapy is considered as the first choice of treatment this disease.Although the rate of occurrence of pseudoaneurysms of the internal carotid artery in post radiation treatment of nasopharyngeal carcinoma is low, it is also a hot topic in department of otolaryngology and doctors because of its dangerous and life?threatening emergencies.In order to improve the level of diagnosis and treatment of the disease, diagnosis, risk, treatment, prognosis and prevention are current summarized in this report. PMID- 29797945 TI - [Autophagy and its research progress in thyroid cancer]. AB - To summarize the autophagy and its research progress in thyroid cancer.In combination with available literatures published in recent years involving the relationship between autophagy and thyroid cancer, the characteristics of autophagy, the role in thyroid cancer were reviewed. The changes of autophagy level will directly or indirectly participate in the pathogenesis and progression of thyroid cancer.Reagents regulating autophagy will have broad prospect of application in thyroid cancer therapy. The autophagy in the thyroid cancer is still poorly understood, and to clarify the molecular mechanism of autophagy and kill thyroid cancer cells by reasonable regulation of autophagy still needs more further studies. PMID- 29797946 TI - [A retrospective analysis of 200-cases of otosclerosis]. AB - Objective:To identify the audiological improvement postoperatively and improve the understand of otosclerosis for a better performance of personalized surgical treatment.Method:We retrospectively reviewed a series of 200 cases after surgery for ototsclerosis.The clinical characteristics,pre-and postoperative audiometric results,signs of Carhart notch, Gelle test and the characteristics of high resolution computed tomography of temporal bone were analyzed retrospectively.Result:73% of patients had tinnitus, while 4% had sense of ear fullness,80.79% had Carhart notch,92.09% had negative result in Gelle test and 45.66% had positive signs on computed tomography. 68% of the patients revealed a type A tympanogram with only 22% type As.Fifty-six cases with laser stapedotomy achieved a the air bone gap at 250 Hz,500 Hz,1 kHz,2 kHz and 4 kHz of 25.54,16.25,13.75,6.34,15.96 dB,respectively. The bone conduction thresholds at 250 Hz,500 Hz,1 kHz,2 kHz improved 2.05,1.51,3.75 and 3.93 dB,respectively. At 4 kHz, bone conduction threshold increased by 1.34 dB.The improvement of bone conduction threshold at 250 Hz,1 kHz,2 kHz was significantly but for the revisions at 500 Hz and 4 kHz.Conclusion:The diagnosis of otosclerosis should be based on the combination of medical history, pure tone audiometry, tympanometry, Carhart notch, Gelle test and high resolution computed tomography of temporal bone.Surgical technique of stapedotomy with Piston artificial auditory ossicle implantation could improve not only the air conduction threshold, but also the bone conduction threshold at 250 Hz,1 kHz,2 kHz. PMID- 29797947 TI - [The clinical value of sleep endoscopy in the diagnosis of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome: a systematic review and Meta-analysis]. AB - Objective:To investigate the clinical value of video laryngoscope in localization diagnosis of upper airway obstruction in OSAHS during drug-induced sleep.Method:We searched the MEDLINE (PubMed), EMBASE, CCTR (The Cochrane Controlled Clinical Trials Register Database), CNKI, WAN FANG databases for randomized, blinded studies according Cochrane systematic review. We chose articles published between 1975 and 2016 about the value of sleep endoscopy in localization diagnosis of upper airway obstruction in OSAHS. All the data were analyzed by the software of the Meta-Disc 1.4.Result:Seven qualitative studies and three quantitative studies were included.A total of three studies with 175 patients met the inclusion criteria for Meta-analysis. Meta-analysis results showed that the merger sensitivity degrees, specific degrees, diagnostic odds ratio, positive likelihood ratio, negative likelihood ratio and 95%CI were 1.0(0.96-1.0),0.71(0.59-0.81),212.47(36.07-1 251.56),4.40(1.28-15.16),and 0.02(0 0.11) respectively. The SROC area under the concentration-time curve (AUC) was 0.991 0.Conclusion:Because of its high accuracy, sleep endoscopy can be used as an important auxiliary examination and the sensitive indexes for the surgery procedures and prognosis treatment plan for OSAHS. But more cohort studies are needed for the verification. PMID- 29797948 TI - [Analysis of reliability and validity of the Chinese version of the Satisfaction with Amplification in Daily Life]. AB - Objective:To investigate the reliability and validity of the Chinese version of the Satisfaction with Amplification in Daily Life (SADL).Method:Ninety adult hearing aid users were evaluated with Chinese version of the SADL.Result:1Reliability:Cronbach's alpha score of overall SADL score was 0.814 and the four subdomains were 0.543-0.824. 2Validity: The correlation coefficients between overall SADL score and the four subdomains were 0.514-0.826(all P<0.01).There were weak or no correlations among the four subdomains. The evaluation of content validity by expertreview showed the questionnaire had good content validity. SADL total scores in bilateral hearing aid userswere significantly higher than those in unilateral hearing aid users (t=2.192,P<0.05).Conclusion:The Chinese version of the SADL meets many psychometric criteria of a robust instrument. It possesses appropriate validity and good reliability, and can be used to measure the outcome for adult hearing aid users in China. PMID- 29797949 TI - [The role of CD4 + CD25 + T regs and CCL17, CCL22 in the pathogenesis of head and neck squamous cell carcinoma]. AB - Objective:To investigate the role of CD4 + CD25 + T regs and CCL17 and CCL22 in the pathogenesis of HNSCC.Method:Twenty cases of HNSCC were enrolled. All patients were primary or recurrent after treatment (chemotherapy, surgery). The primary tumor was taken as the experimental group, and the adjacent normal tissues from the primary tumor 1-3 cm were taken as control group. CD4 + /Foxp3 and CD25+/Foxp3 were detected by immunofluorescence, while CCL17 and CCL22 were detected by ELISA. The difference and correlation between the amount of CD4+,CD25+ and the expression of CCL17, CCL22 were observed and analyzed.Result:The difference of mean optical density between CD4+/Foxp3 and CD25+/Foxp3 was statistically significant between the experimental group and the control group (P<0.05). The concentration of CCL17 and CCL22 was statistically different between the two groups (P<0.01). There was a positive correlation between CD25+and CCL17,CCL22(r=0.595, 0.720,P<0.01).Conclusion:CD4+CD25+T regs and CCL17,CCL22 played an important role in the pathogenesis of head and neck squamous cell carcinoma,both of which interacted with each other,and promoted the recurrence and metastasis of HNSCC. PMID- 29797950 TI - [Preliminary findings for metabolite profiles of papillary thyroid carcinoma and laryngeal squamous cell carcinoma]. AB - Objective:To identify distinct metabolite profiles of papillary thyroid cancer (PTC) and laryngeal squamous cell carcinoma (LSCC).Method:Tumor and adjacent non tumor specimens were collected from 57 PTC and 33 LSCC patients. Distinct metabolite profiles of tissues were examined using a combination of gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. The data were analyzed with multivariate statistical analysis to compare the distinct metabolite profiles and related pathways of these three tumors.Result:A panel of 46 and 41 differentially expressed metabolites were identified in tumor and adjacent non-tumor tissues of PTC and LSCC, respectively. Increased glycolysis, amino acids metabolism, one carbon metabolism and tryptophan metabolism were found in these two types of tumor tissues compared to adjacent non tumor tissues. Purine and pyrimidine metabolism was significantly elevated in PTC and LSCC tumor tissues, while taurine and hypotaurine were only higher in PTC tumor tissues. The fatty acid metabolism was detected at lower level in both PTC and LSCC tumor tissue.Conclusion:PTC and LSCC tumor tissues not only have common metabolic signatures characterized by increased glycolysis, amino acids metabolism, one carbon metabolism and tryptophan metabolism, but also have distinct metabolic signatures. It is helpful to understand the nature of these two tumors. PMID- 29797951 TI - [Suture under tension across cartilage in the application of the crooked nose surgery]. AB - Objective:Observing the effect of maintain tension across suture between cartilages to fix new nasal structure on balance the asymmetric strength of the two sides of the cartilage and the recurrence of the postoperative crooked nose.Method:A L-shaped struct made of the nasal septum cartilage were fixed to maintain tension across structure between cartilage during rhinoplasty in 39 patients with crooked nasal deformity. Of 21 cases were type I deviation, of 12 cases were C-shaped deviation,and of 6 cases were S-shaped deviation.Result:A 1-5 years follow-up were performed. The effects were divided into three degrees: 30 cases excellent (76.92%), 6 cases good (15.38%) and 3 cases acceptable (7.69%).The rate of excellent and good was 92.31%(36/39). The type I improvement rate was 80.3%,the rate of type C was 83.6% and the improvement rate of type S was 84.1%,the overall improvement rate was about 81.9%.Conclusion:Suture under tension across cartilage can fix reconstruction of nasal structure effectively,improve the postoperative effect, reduce recurrence of crooked nose. The operation is simple and is an essential part of the nasal deformity correction technique. PMID- 29797952 TI - [The relationship between pathology and imaging overview in pediatric nasal tumors]. AB - Objective:To study the clinical features and nasal image of children with nasal tumors.Method:The samples of 40 cases of pediatric nasal tumors, which were diagnosed based on pathology, were collected. Clinical features, pathological histology and imaging characteristics were also summarized.Result:There were 23 cases of benign tumors and 17 cases of malignancy. The most common benign tumors were angiofibroma (7 cases), capillary hemangioma (4 cases) and ossifying fibroma (4 cases), while the most common malignant tumors were lymphoma (10 cases) and embryonal rhabdomyosarcoma (3 cases). In all cases, 10 tumors arose from sinus, 7 tumors limited in the nasal cavity or nasal vestibule, 8 tumors located in sinonasal, 10 tumors are originated from nasopharyngeal area and (or) postnaris, 3 cases located in the lateral nasal, 2 cases located in the nasal septum. CT or MRI found that 13 cases showed bone destruction, 5 cases showed bone absorption, 14 cases involvement of adjacent structure, 6 cases with cervical lymph node enlargement.Conclusion:The common nasal tumors in children include lymphoma, angiofibroma, capillary hemangioma, ossifying fibroma and embryonal rhabdomyosarcoma. Clinical manifestations of pediatric nasal tumors were atypical, the diagnosis mainly dependent on pathology and imaging examination. CT and MRI examination can well depict the site of tumors, the bone change of the around situation and the encroachment of the tumor accurately, and may play an important role in clinical diagnosis and staging of the tumors, constituting the treatment plan and prognosis evaluation. PMID- 29797953 TI - [A study of 16 cases on the island pectoralis major muscle flap in repair for the defects after the laryngeal function reserved operation of hypopharyngeal carcinoma]. AB - Objective:To explore the application about island pectoralis major muscle flap in repair for the defects after the laryngeal function reserved operation of hypopharyngeal carcinoma.Method:A retrospective analysis about 16 patients who underwent hypopharyngeal carcinoma surgery using pedicle island pectoralis major myocutaneous flap to repair, including 14 cases whose primary tumors located in the piriform fossa, and 2 cases in pharynx posterior wall.Result:All 16 cases' pectoralis major muscle flap survived, 2 of patient appeared to have a pharyngeal fistula, but recovered after transition. Of the 16 cases, 14 cases were removed the trachea tube in 1-3 months, 2 cases survive with tube, and all patients were satisfied with their appearance and the function. In 16 cases, 2 of them survived 3 and a half years, died of lung metastasis; 2 cases survived for four years, 1 died of local recurrence of tumor and another died of heart disease; 1 survived for four and a half years and died of lung metastasis; the remaining 11 cases were still in follow-up.Conclusion:The application in the surgical defect repair of pharyngeal carcinoma with pedicle island pectoralis major myocutaneous flap is safe and effective. PMID- 29797954 TI - [Expression difference of connexins in neural cells of Cx26 deficiency deafness]. AB - Objective:Using induced pluripotent stem cell (iPSC) technology, neural cells from Cx26 deficiency deafness patients were derived, to investigate the influence of Cx26 deficiency on neural development and gene expression.Method:Fibroblasts were taken from profound deaf patients caused by Cx26 deficiency, and were induced to non-integration induced pluripotent stem cell lines, whose morphology, internal and external gene expression were characterized. Then these iPSC lines were differentiated into neural cells, whose expression change of pluripotent genes, neural markers and connexin genes were investigated.Result:Three iPSC lines with Cx26 deficiency were successfully established and differentiated into neural progenitor cells and neurons. The iPSC lines showed similar morphology, proliferation, internal and external gene expression with human embryonic stem cells. In iPSC-derived neurons, expression of Cx32 was up-regulated obviously, expression of Cx36 was up-regulated slightly, and expression of Cx26 showed no obvious change.Conclusion:TNeural differentiation of IPSC is not influenced by Cx26 deficiency, but expression of Cx32 and Cx36 are up-regulated, which may hint compensation from Cx32. PMID- 29797955 TI - [Clinical treatment effect of glucocorticoids and extract of ginkgo biloba on post-viral olfactory dysfunction]. AB - Objective:To observe the effect of ginkgo biloba extraction combined with glucocorticoids on postviral olfactory dysfunction.Method:Forty-two patients were diagnosed as postviral olfactory dysfunction. All patients underwent olfactory test, including T&T test and Sniffin Sticks test before and after treatment. The treatment lasted up to 3 months based on effectiveness. The results of olfactory test were recorded every month.Result:Twenty patients received the treatment with prednisone acetate. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 25.00%(5/20) and 45.00%(9/20),respectively; Sniffin Sticks test showed that the effective and improvement rate of the treatment were 20.00%(4/20)and 50.00%(10/20),respectively. Twenty-two patients received the treatment combined with extract of ginkgo biloba. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 31.82%(7/22)and 50.00%(11/22),respectively; through Sniffin Sticks test showed that the effective and improvement rate of the treatment were 27.27%(6/22)and 54.55%(12/22),respectively.Conclusion:Olfactory function in patients with postviral olfactory dysfunction was improved with two therapy. There was no significant difference on effect between the two therapeutic groups, but the effect of combination of extract of ginkgo biloba was better than the effect of prednisone acetate. Prolong duration of treatment is help for the recovery of the olfaction. PMID- 29797956 TI - [The effect of monrustet on the exhalation of nitric oxide and inflammatory cytokines in patients with asthma combined with OSAHS]. AB - Objective:To study the effect of monrustet on fractional exhaled nitric oxide and inflammatory cytokines in the elderly with bronchial asthma combined obstructive sleep apnea hypopnea syndrome.Method:150 cases diagnosed as asthma were enrolled in this study. The patients were divided into bronchial asthma combined with OSAHS (n=72)and bronchial asthma (n=78). According to the different treatment methods , patients were divided into observation group and control group. Two groups were given common treatment with inhaled corticosteroids, and the observation group was taken orally montrast 10mg/night additionally. The fractional exhaled nitric oxide was detected before and after treatment. Serum were collected for detection of tumor necrosis factor alpha (TNR-alpha), Creactive protein (CRP) and interleukin 6 (IL-6), according to the sleep monitoring results, the sleep apnea low ventilation index (AHI) was calculated, and the changes of FeNO level,CRP,TNR-alpha,IL-6 and AHI were analyzed in the two groups.Result:Before treatment, the gender, age, degree of disease, FeNO level,TNR-alpha, CRP,IL-6 and AHI differences were not statistically significant in the two groups (P>0.05).After treatment, both groups of FeNO, TNR-alpha,CRP,IL 6 and AHI decreased before treatment (P < 0.05).The observation group was lower than the control group, and the difference was statistically significant (FeNO level, AHIP< 0.01,TNR-alpha, CRP,IL-6 P< 0.05).Conclusion::Montelukast can reduce the FeNO level, the expression of TNR-alpha, CRP, and IL-6 of patients of bronchial asthma combined with OSAHS. Further improvement of the patient's condition, and provide reference value for the clinical medicine of patients with asthma. PMID- 29797957 TI - [The sodium salicylate affects the expression of NMDA receptor and GABAa receptor subunits in spiral ganglion neurons of the cochlea through DA receptor]. AB - Objective:To investigate mRNA expression of dopamine receptor subtypes in the rat cochlear spiral ganglion neurons (SGN) following exposure to the sodium salicylate. In addition, we observed the effect of sodium salicylate on N methyl D-aspartic acid (NMDA) receptor subunit NR1 and gamma aminobutyric acid (GABA)a receptor subunit GABRalpha2 mRNA under the circumstance of DR activation or blocking. Moreover, we also focused on the the interaction between receptors mediated by SS.Method:Immunofluorescence techniques were applied to detect DR (DR1 and DR2) expression in cultured rat SGN. Moreover, RT-PCR was performed to assess NR1 and GABRalpha2 subunit mRNA.Result:Immunofluorescence images showed co localization of DR1/DR2 and betaIII-tubulin protein in SGN bodies and axons. RT PCR results illustrated that 1DR subtypes of DRd1-5 were detected in the SGN. 2The mRNA expression of all subtypes of DR and GABRalpha2, NR1 subunits were obviously upregulated except DRd3 after treatment with sodium salicylate. Among them, DRd1 expression increased 34.64%(t=-5.123,P=0.007),DRd2 expression increased 34.60%(t=-5.206,P=0.006),DRd4 expression increased 20.87%(t= 3.337,P=0.029),DRd5 expression increased 26.42%(t=-6.054,P=0.004),GABRalpha2 expression increased 30.41%(t=-2.839,P=0.047),NR1 expression increased 39.22%(t= 6.243,P=0.003).3After exposure to sodium salicylate (5 mmol/L), dopamine (100 MUmol/L), DR1 agonist (SKF38393,20 MUmol/L), DR2 agonist (Quinpirole,20 MUmol/L), GABRalpha2 expression increased 21.78%,27.45%,33.02%,33.42% respectively (F=12.399,P=0.001),and NR1 expression increased 28.70%,26.82%,29.03%,35.05%(F=50.395,P=0.000) respectively.4Compared with the group of sodium salicylate treatment alone, both sodium salicylate + DR1 antagonist (SCH23390,20 MUmol/L) group and sodium salicylate + DR2 antagonists (Eticlopride,20 MUmol/L) group had a suppression on GABRalpha2 and NR1 mRNA expression.GABRalpha2 mRNA reduced 29.56%,37.10%(F=22.101,P=0.000) and NR1 mRNA expression decreased 37.62%,32.83% respectively(F=72.933,P=0.000).Conclusion:Most of the DR subtypes mRNA expression in SGN were increased following exposure to sodium salicylate. DR may be involved in the effect of sodium salicylate on GABAaR and NMDAR mRNA expression. PMID- 29797959 TI - [Perioperative management of subglottic foreign body in children]. PMID- 29797960 TI - [3 case of pharyngeal cold abscess and literature review]. PMID- 29797958 TI - [Establishment and characterization of an orthotopic murine model of mucosal malignant melanoma of the maxillary sinus]. AB - Objective:To establish a stable and reliable orthotopic murine model of mucosal malignant melanoma of the maxillary sinus so as to provide animal models for further studying for pathogenesis and therapy of sinonasal malignancy.Method:B16 were implanted in the right maxillary sinus of male nude mice. After tumors appeared in right maxillary sinus, tumor growth and survival rate were recorded. The degree of tumor infiltration was observed through the MRI.Result:Mice with B16 implanted in right maxillary sinus developed primary tumors. The survival and the tumor volume were related to the number of tumor cells implanted. We found that the tumor can invade into nasal cavity, orbital cavity and the basilar region using MRI.Conclusion:We successfully established a model for mucosal malignant melanoma of the maxillary sinus. This model offers an experimental tool for further research on biological characteristics of sinonasal malignancy and the development of new therapy. PMID- 29797961 TI - [A case report of plasma cell granuloma in maxillary sinuses]. AB - Plasma cell granuloma is a kind of the disease with low incidence at head and neck,which is a benign lesions with malignant biological performance. The diagnosis of plasma cell granuloma is difficult as the symptom is not typical and it is difficult to distinguish with cancers and other diseases through the physical sign and imaging manifestation. The golden standard of diagnosis is histopathological examination. The therapy of plasma cell granuloma is still controversial, but the first choice is the operation. The other therapy such as hormone therapy, radiotherapy, chemotherapy etc., should be applied according to special conditions. Surgery has advantage with high cure rate and very low reoccurance rate. In this paper, we reported a case of plasma cell granuloma, occurred in maxillary sinus and summarizes the experiences about diagnosis and therapy of plasma cell granuloma in maxillary sinus through review previous literature. PMID- 29797963 TI - [Research progresses in vestibular rehabilitation]. AB - Vestibular rehabilitation is one of the treatments of vertigo, which major based on vestibular exercise. Unlike general exercise, it is a highly specialized designed method without medication or traumatic. Vestibular rehabilitation includes peripheral rehabilitation,central rehabilitation, alternative rehabilitation, visual conflict rehabilitation and fall prevention rehabilitation. The cross-coupling mechanism of vestibular reflex is the basis of vestibular compensation. The characteristics of visual reflex and the proprioception mediated cervical reflex are the foundation of alternative rehabilitation, and cognitive mechanism is the basis of all kinds of vestibular rehabilitation. Data about the safety and efficacy of vestibular rehabilitation are provided during the past several decades. Various tests and measures are used for examination and determine their ability to participate in their environment, as well as various treatments are described. Factors that affect recovery are noticed to prognosticate recovery. This review focuses on the rehabilitation mechanism, clinical application, related inspection and evaluation, and influence factor of vestibular rehabilitation. PMID- 29797962 TI - [Orbital decompression for intraorbital hematoma after surgery of recurrent nasal polyps: a case report]. AB - A case of intraorbital hematoma after surgery of recurrent nasal polyps in August 2016 was reviewed. The patient underwent emergent orbital decompression after intraorbital hematoma, and followed up for half a year. The eyeball blood stasis of the case had gradually vanished. Ocular movement and vision of the left are still normal now. Orbital decompression is both necessary and effective for intraorbital hematoma after surgery of nasal endoscope. PMID- 29797964 TI - [Diagnosis and management of spontaneous cerebral spinal fluid otorrhea]. AB - Spontaneous cerebral spinal fluidotorrhea (SCSFO) is a type of CSF otorrhea without obvious causes including previous trauma, surgery, infection or neoplasm. The etiology of SCSFO remains unclear, the diagnosis can be overlooked because of the untypical clinical features. In this paper, we reviewed etiology, clinical features, diagnosis and therapy of SCSFO from recent relative literatures. PMID- 29797966 TI - [Re-recognition of the significance of perioperative management of chronic sinusitis]. PMID- 29797965 TI - [Clinical features and advanced progress of secondary BPPV]. AB - BPPV is a disease provoked by abrupt head movements, results in short paroxysmal vertigo or nystagmus. These patients often can accurately describe the dizziness happened when they head move suddenly, especially when looking upward, turning over in bed, lying down, or bending over. BPPV is divided into idiopathic BPPV and secondary BPPV, in most cases. The underlying cause cannot be determined, which is called idiopathic; however, in 30% patients, BPPV may be attributed to a specific cause and is termed secondary BPPV. We reviewed the pathogenesis, mechanisms, clinical features, treatment and the latest progress of secondary BPPV. PMID- 29797967 TI - [The application of endoscopic strategy and approaches to treat sphenoid sinus inflammatory diseases]. AB - Objective:A retrospective study aimed to investigate the characteristics and prognosis of inflammatory sphenoid sinus diseases and discuss of endoscopic surgical techniques.Method:A total of 105 subjects with isolated inflammatory sphenoid pathologies were treated by endoscopic surgery,which included 41(39.0%) cases of fungal sinusitis,33(31.4%) mucocele,and 31(29.5%) sphenoiditis.They were evaluated by paranasalsinuse CT scan and all patients underwent endoscopic sphenoidsinus surgery under general anesthesia.Twenty cases were selected in Messerklinger,74 cases selected in Wingand,5 cases selected in Draf 3-like,5 cases selected in transphenoidal septum into the contralateral sphenoid sinus,and 1 case selected in trans-medial plate of pterygoid process approach.Result:The postoperative follow up from 6 to 27 months showed that sphenoid ostium were good in 96(91.4%) patients,stenosis in 5(4.8%) patients,and atresia in 4(3.8%)patients who need reoperation.Conclusion:Transnasal endoscopic sphenoidectomy should be the standard option for dealing with isolated inflammatory sphenoid diseases.The five different approaches would be selected according to the extension of the diseases and anatomic structure of the sphenoid sinus. PMID- 29797968 TI - [Extended inferior meatal approach by reversing inferior turbinate for maxillary sinus and adjacent lesions]. AB - Objective:The aim of this study is to explore the feasibility and results of surgical removal of maxillary sinus and adjacent lesions via extended inferior meatal approach by reversing inferior turbinate.Method:Among these 28 cases,there were 9 cases of maxillary cysts(4 of which with oroantral fistula),2 cases of odontogenic maxillary sinusitis(1 of which with oroantral fistula),3 cases of maxillary sinus cysts,2 cases of antrochoanal polyps,5 cases of maxillary sinus inverted papilloma,1 case of maxillary sinus inverted papilloma with infiltrative squamous cell carcinoma(moderately differentiated),4 cases of inferior orbital fracture,1 case of anterior maxillary sinus wall fracture,and 1 case of infratemporal fossa cysts with fungal maxillary sinusitis.All operations were conducted via extended inferior meatal approach.Result:All patients did not have intraoperative complications,and were free of recurrence after the 3 to 36 months postoperative follow-up.Conclusion:The extended inferior meatal approach by reversing inferior turbinate can deal with all aspects of the maxillary sinus and retromaxillary lesions.This procedure has a clear vision and high successful rate. PMID- 29797969 TI - [Efficacy analysis of endoscopic stage I reconstruction of nasal contour and function]. AB - Objective:The aim of this study is to assess the effectiveness of endoscopic stage I reconstruction of nasal contour and function.Method:Twenty subjects with severe nasal trauma,nasal bone fracture and deviation of nasal septum were selected.The surgeries of stage I reconstruction of nasal contour and function were proceeded on 7 to 30 days after trauma.Result:The VAS scores of deformity of nasal contour and severity of nasal blockage assessed by patients decreased significantly after operation.Deflection distance of nasal dorsum measured by 3D imaging decreased significantly.In patients with abnormal nasal ventilation,the volume and the minimal cross-section area of abnormal nasal cavity increased significantly(P<0.05).Conclusion:The effectiveness of endoscopic stage I reconstruction of nasal contour and function was excellent.The patients were satisfied with improvement of nasal contour and ventilation. PMID- 29797970 TI - [Prevention and treatment of sinusitis complicated by surgical treatment of pituitary adenoma]. AB - Objective:The aim of this study is to study the reason,prevention and cure measures of sinusitis complicated by frontal craniotomy or endoscopic transnasal approach in surgical treatment of pituitary adenoma.Method:A total of 10 patients with sinusitis complicated by surgical treatment of pituitary adenoma were admitted.Five sphenoid sinusitis patients and 2 frontal sinusitis patients weretreated with nasal endoscopic surgery,while 3 cases frontal sinusitis patients were received nasal endoscopic surgery combined with surgery outside nose.Result:The following up for 5 to 20 months showed that 9 cases were cured and 1 case was improved.There were no cerebrospinal fluid leak and other complications.Conclusion:The sinusitis after frontal craniotomy or endoscopic transnasal approach in surgical treatment of pituitary adenoma may be related to the mishandling of frontal sinus or sphenoid sinusitis and the existence of the foreign matter such as bone wax and fascia.We should clear the foreign matter and inflammatory granulation tissue to ensure that sinus drainage.According to the specific situation of the patients,good prognosis can be obtained by nasal endoscopic surgery merely or combined with surgery outside nose. PMID- 29797972 TI - [Clinical characteristics and surgical treatment of types II to IV external auditory canal cholesteatoma]. AB - Objective:The aim of this study is to explore the clinical characteristics,diagnostic methods,surgical procedures and results of typesII to IVexternal auditory canal cholesteatoma.Method:In the 63 cases,there were 39 patients suffering typeIIexternal auditory canal cholesteatoma,22 patients suffering typeIII and 2 patients suffering type V.All patients had surgeries to remove the lesion under the microscope,and underwent canaloplasty or tympanoplasty or modified mastoidectomy as well.Result:There were 2 cases occurred meatal stenosis postoperatively ,as well as 2 cases of cholesteatoma recurrenced,and were cured after second operation.Four patients'hearing level were not improve postoperatively due to the severe damage of their ossicular chain.All other patients were cured with one operation,which the cavity with good skin coverage and there has been no recurrence.Conclusion:Temporal bone CT scan has important significance in the diagnosis and classification of external auditory canal cholesteatoma.Prevention and early diagnosis are particularly important.Surgical treatment should completely remove the lesion,restore hearing according to the situation,and appropriate surgical treatment should be taken according to the classification,location of external auditory canal cholesteatoma as well as hearing level of patients. PMID- 29797971 TI - [The impacts of endoscopic sinus surgery with middle turbinate and superior turbinate resection on quality of life and olfactory function in patients with chronic rhinosinusitis with nasal polyps]. AB - Objective:The aim of this study is to investigate the impacts of endoscopic sinus surgery(ESS) with middle turbinate and superior turbinate resection on quality of life and olfactory function in patients with chronic rhinosinusitis with nasal polyps(CRSwNP) and with dysosmia. Method:All of the 81 patients with CRSwNP and with dysosmia recieved ESS with middle turbinate and superior turbinate resection.The patients were given standardized drug treatments during the preoperative period,such as nasal irrigation,using local hormone spray,mucus decorporation agent by oral,using macrolide antibiotics according to the circumstances and so on.We used SNOT-20 to evaluate the quality of life preoperatively and postoperatively in patients;and used the T&T olfactory testing and VAS to evaluate the olfactory function of the patients.Result:The SNOT-20 test showed that "need to blow nose", "lack of a good sleep", "thick nasal discharge", "difficult to go to sleep",and "awkward" influence on the quality of life severely.The scores of all items showed decreasing tread in 2 weeks,1 month and 3 months after operation(P <0.05).Olfactory:Among the 81 patients(162 side),54 patients(108 sides) lost sense of smell completely in preoperative period and 27 patients' olfaction lost in varying degrees(10 patients are bilateral symmetry hyposmia and 17 patients are bilateral asymmetry hyposmia).Compared with the preoperative period,70 patients'(86.4%) olfactory function were improved at 3 months after the operation,in which 43 patients'(53.1%) olfactory function recovered to normal,and 27 patients'(33.3%) olfactory function improved in varying degrees;however,11 patients'(13.6%) olfactory function had not improvement at all.Sixty-one patients were followed up for more than one year.One year after operation,53 patients'(86.9%) olfactory function were improved,in which the 31 patients' (50.8%) olfactory function recovered to normal and 22 patients'(36.1%)olfactory function improved in varying degrees;8 patients'(13.1%) olfactory function had no improvement;the remaining 20 patients are being followed up.There was a significant difference between preoperative T&T olfactory testing and postoperative's(P <0.05);and so was VAS assessment(P <0.05). Conclusion: For the patients with CRSwNP and with dysosmia,the operation of ESS with middle turbinate and superior turbinate resection combined with standardized drug treatment in preoperative period can effectively improve the patients' quality of life and olfactory function.Hyperventilation and nasal dryness caused by excessive resection were not found. PMID- 29797973 TI - [Application of gadolinium enhanced magnetic resonance imaging of inner ear to observe bilateral inner ears hydrops in patients with unilateral Meniere's disease]. AB - Objective:Department of Otolaryngology Head and Neck Surgery,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai Jiaotong University Ear Institute,Shanghai,200092,China This study was designed to study the correlation between endolympahatic hydrops image results and auxiliary examinations by magnetic resonance imaging after intratympanic administration of gadolinium in both ears in unilateral Meniere's disease patients.Meanwhile,the contralateral endolympahatic hydrops of the "asym ptomatic " ear in patients with unilateral Meniere's was also observed.Method:Thirty-one patients with unilateral Meniere's disease were enrolled in this study.All the patients underwent pure tone audiometry,electrocochleography(ECochG),cervical-vestibular evoked myogenic potentials(cVEMP) before intratympanic gadolinium contrast agents injected.All the patients underwent three-dimensional fast fluid attenuated inversion recovery sequence magnetic resonance imaging(3D-FLAIR MRI) after intratympanic gadolinium contrast agents injected 24 hours.The images were graded in accordance with the severity of endolympatic hydrops.Spearman correlation analysis was performed between the scores of the images and results of auxiliary examination results.Meanwhile,Student's t test was performed for the significance test of the age,duration of the disease and the hearing level of the affected ears between the group with contralateral endolympatic hydrops and the group without contralateral endolympatic hydrops.Result:Pure tone average and the degree of the cochlear hydrops(r=0.383,P <0.05),the SP/AP ratio and the degree of the cochlear hydrops(r=0.496,P<0.01),and interaural amplitude difference and the degree of the vestibular hydrops(r=0.635,P<0.01) showed a significant correlation.The duration of the disease[(6.7+/-6.3) years vs(2.9+/-3.1) years,P <0.05] and the hearing level of the affected ear[(70.3+/-7.4)dB vs(52.5+/-3.8)dB,P <0.05)] showed a significant difference between the group with contralateral endolympatic hydrops and the group without contralateral endolympatic hydrops.Conclusion:Pure tone average and the degree of the cochlear hydrops,-SP/AP ratio and the degree of the cochlear hydrops,and interaural amplitude difference and the degree of the vestibular hydrops also showed a significant correlation,which suggesting that MRI image can reflect the auditory-vestibular function in patients with Meniere's disease.Endolympatic hydrops and hearing loss are closely related,but not necessarily result in Meniere's disease symptoms.Patients with longer duration of the disease and worse hearing in the affected ears are more likely to develop bilateral endolympatic hydrops. PMID- 29797974 TI - [Association between obstructive sleep apnea hypopnea syndrome and type 2 diabetes in Chinese:a Meta analysis]. AB - Objective:The aim of this study is to assess the association between obstructive sleep apnea-hypopnea syndrome and type 2 diabetes (T2DM).Method:Databases such as Chinese Biomedical Literature Database,PubMed,Chinese Academic Journals full-text database,Wanfang Resource Database and Chongqing VIP have been searched to collect literatures about the relationship between OSAHS and type 2 diabetes.The papers and unpublished articles were also manually retrieved.Randomized controlled trial conformed to the condition were evaluated according to the standards of literature assessment,and the data has been extracted.The RevMan5.3 software was applied to carry out Meta-analysis.Result:Thirty studies are includedin the Meta-analysis.The fasting glucose content of OSAHS patients with T2DM is significantly higher than T2DM patients[WMD=1.01,95%CI(0.55,1.46), P<0.01];OSAHS with T2DM patients' apnea hypopnea index is significantly higher than OSAHS patients[WMD=3.78,95%CI(1.69,5.87),P<0.01];the fasting glucose content of OSAHS patients is also significantly higher than normal [WMD=1.16,95CI%(0.88,1.44),P<0.01];When stratified by rhe grades of OSAHS,we found fasting glucose content of all OSAHS patients is significantly higher than normal[WMD=1.09,95CI% (0.97,1.21),P<0.01];the funnel flot appeared to be symmetrical with little bias.Conclusion:The experimental results indicate that OSAHS is significantly related with T2DM ,and they may be the risk factorof each other. PMID- 29797975 TI - [The inflammatory pattern and the characteristics of mucous remodeling in different immune type of nasal polyps]. AB - Objective:The aim of this study is to study the different immune-type of polyps and valuate mucosal inflammatory pattern and remodeling features between in IL-5 positive vs.IL-17 positive nasal polyps.Method:Nasal polyp or nasal turbinate tissue was obtained from 88 CRSwNP patients during endonasal sinus surgery or 18 non-atopic control subjects during septoplasty,respectively.Assessment of pro inflammatory cytokines and mediators by ELISA.Additionally,the distribution of IL 5 positive or IL-17 positive cells and inflammatory cells(eosinophil,neutrophil,etc.) were examined using immunohistochemistry(IHC).Result:Overall more than half amount of polyp tissue did not express any TH cells key cytokine.However there are 21% polyp present IL 5 positive and 16% of IL-17 positive as well as 9% of IFN-gamma positives.Amount of them that IL-17 positive polyps by synthesis of mediators promoting neutrophilic inflammation[myeloperoxidase(MPO),IL-1beta,IL-6 and IL-8)] and staining infiltration of MPO positive with IL-17 positive cells,whereas IL-5 positive nasal polyps were characterized by synthesis of mediators promoting eosinophilic inflammation(IL-5,ECP,TIgE,and SAE-IgE) and infiltrating of eosinophils and IL-5 positive cells.Meanwhile TGF-beta1 and MMP7 protein levels enhanced in IL-17 positive polyps and decreased in IL-5 positive than control.Conclusion:Nasal polyps presenting as different immune types and there were characterized with different inflammatory and remodeling patterns.Amount of them that IL-17 positive polyps presenting as a neutrophilic inflammation with remodeling biased.Whereas IL-5 positive nasal polyps were characterized by eosinophilic inflammation and absence of remodeling tendency. PMID- 29797976 TI - [Prognosis analysis of multidisciplinary treatment on nasal mucosa malignant melanoma]. AB - Objective:The aim of this study is to investigate the facters affecting prognosis of primary sinonasal mucosal malignant melanoma and analyze the optimal therapeutic strategies.Method:Among the 33 patients with sinonasal mucosal malignant melanoma,twenty-six patients received surgical treatment,nineteen patients accepted radiotherapy,and twenty-one patients had the biotherapy.The Kaplan-Meier and log-rank methods was used to assess the prognosis of different treatment.Result:the patient's 3-year-survival rate was 48.3% and 5-year-survival rate was 30.3%.Surgical treatment is the important factor for the 5-year-survival rate(P <0.05),while the chemotherapy and biotherapy had no effect on overall survival rate(P>0.05).Conclusion:The surgical treatment is the preferred method of treatment,and endoscopic surgery has the satisfactory effect.Adjuvant radiotherapy can improve local tumor control rates.Immunotherapy is the development direction of treatment for nasal mucosal malignant melanoma. PMID- 29797977 TI - [The imaging analysis of the age-related changes on maxillary sinus]. AB - Objective:The aim of this study is to investigate the age-related changes rules of maxillary sinus.Method:The 540 patients (1 080 sides) with normal data of deputy sinus in spiral CT were enrolled,including 270 cases of male and female,age from 7 to 81 years old.They are divided into 9 groups according to the age:Group A at the age of 7-12 years old,Group B at the age of 13-17,Group C at the age of 18-20 years old,Group D at the age of 21-24 years old,Group E at the age of 25-28 years,Group F at the age of 29-35 years old,Group G at the age of 36 40 years old,Group H at the age of 41-65 years old,and Group I is more than 65 years old.By the gender,the patients in each group was divided into male and female groups.There are 30 cases in each group(60 sides).The volumes and the three-dimensional diameters of the maxillary sinus were measured,and the coefficient of gasification of them were calculated.Result:The maxillary sinus volume and 3 D lines have almost the same change trend along with the age between the male and female group;From 7 to 20 ages,they are increased linearly,13 to 17 fastest-growing;18 to 20 years old reached to peak;declined slightly in 21-28 years old,29-35 a second growth peak,and 36 to 40 years old have fallen sharply,to reaching a steady state after 41 years old;The gasification coefficient has no difference among all groups.Conclusion:The volume changes with the age-related on maxillary sinus is in the adolescent stage.It reaches a steady state in the middle and old age stage,and gasification coefficient on maxillary sinus has no age-related changes among all groups. PMID- 29797978 TI - [Clinical value of a domestic portable monitoring system for the diagnosis of obstructive sleep apnea syndrome]. AB - Objective:The aim of this study is to evaluate the clinical value of a portable monitoring system(YH600B) in OSAHS by comparing the consistency of overnight sleeping data recorded by polysomnography and YH600B. Method:One hundred and nineteen snoring patients underwent one-night polysomnography(PSG)and YH600B simultaneously.The measured data by the two methods were compared to analysis their correlation,including AHI and LSaO2.The Bland Altman plots was used to assess the consistency between PSG and STD.Sensitivity and specificity comparisons were plotted graphically using receiver operating characteristic(ROC) curve analysis.Result:All cases were well tolerated the procedure.1AHI and LSaO2 measured by the two techniques have strong correlation(r=0.981, r=0.882,P<0.05,respectively).2Bland Altman analyses showed strong agreement between AHI values from the YH600B and PSG recordings.3the ROC-curve showed that AHI cut off value was 7.25,area under the curve was 0.992 3,sensitivity was 98.1%,and specificity was 92.2%.Conclusion:These data suggest that YH600B have highly consistency with PSG,and YH600B is accurate in the application of the diagnosis of OSAHS. PMID- 29797979 TI - [Treatment of isolated sphenoid sinus disease by trans-basal lamella approach to sphenoid sinus]. AB - Objective:The aim of this study is to investigate the safety and practicability of the trans-horizontal basal lamella sphenoidotomy approach in the treatment of the isolated sphenoid sinus disease.Method:Sphenoidotomy and posterior ethmoidotomy by endoscopic trans-horizontal basal lamella approach were performed in 64 patients who were diagnosed with isolated sphenoid sinus.The horizontal course of the basal lamella is perforated and opened,and the superior meatus is entered.Then sphenoidotomy and posterior-ethmoidotomy were performed by the landmark superior turbinate.Result:All patients were successfully operated without serious complications.After 1 year follow-up,no recurrence were found in 30 cases of fungal sphenoid sinusitis patients,12 cases of chronic sphenoidal sinusitis patients,13 cases of sphenoid sinus cyst patients,6 cases of sphenoid sinus polyps patients,and 3 cases of sphenoid sinus inverted papilloma patients.The ostium of sphenoid sinus maintained well without atresia.Conclusion:Trans-horizontal basal lamella approach to sphenoid sinus is safe and effective in the treatment of isolated lesion,and the opening of sphenoid sinus and posterior-ethmoid sinus were enlarged better by this technique. PMID- 29797981 TI - [The clinical treatment experience of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant in 82 cases]. AB - Objective:The aim of this study is to explore the treatment of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant.Method:Eighty-two patients with diagnosis of low-middle frequency sudden sensorineural hearing loss were selected;All patients were randomly divided into systemic steroid therapy group and steroid combined with dehydrant therapy group.All patients received Alprostadil,Ginaton and Mecobalamin.Intravenous steroids was given in systemic steroid therapy group,while intravenous steroids and dehydrant were given in steroid combined with dehydrant therapy group.Finally,the results were collected and analyzed.Result:The total effective rate was 92.31% in systemic steroid therapy group,and 93.02% in steroid combined with dehydrant therapy group.There is no significant difference between the twogroups(P<0.05).The average time of hearting recovery was (7.03+/-1.22)days in systemic steroid therapy group,while(6.17+/ 1.15)days in steroid combined with dehydrant therapy group,and significant difference was detected between the two difierent treatments(P<0.05).Conclusion:The treatment of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant can achieve a favorable prognosis,and may shorten the treatment time. PMID- 29797980 TI - [Endoscopic septoplasty combined with nasal bone reduction for the treatment of nasal bone fracture complicated with nasal septum deviation]. AB - Objective:The aim of this study is to discuss the methods and effect of one-stage operation in the treatment of nasal bone fracture complicated with nasal septum deviation.Method:Forty cases of nasal bone fracture complicated with nasal septum deviation patients received nasal endoscopic septoplasty combined with nasal bone reduction.All cases were followed up for 6 months or more.Resuslt:Forty cases of patients had smooth nasal airway,satisfactory nasal appearance and no collapse of nose bridge or septum perforation.Conclusion:The endos-copic septoplasty combined with nasal bone reduction can be simultaneously used in the treatment of nasal bone fracture complicated with nasal septum deviation in early stage.The operation has the advantages of good vision,accurate operation,minimally invasive and less complications. PMID- 29797982 TI - [The application of 3D simulationtemporal-bone-system for temporal bone anatomy training]. AB - Objective:The aim of this study is to investigate the application of 3D simulation temporal-bone-system for temporal bone anatomy training.Method:3D simulation temporal-bone-system in the anatomy workshop was introduced in Beijing Children's Hospital from 2014 to 2015.Each participant was trained by cadaver dissection and 3D simulation temporal-bone-anatomy,and they also completed the questionnaires and evaluated the procedure.Then the difference was analyzed.Result:1In stage of mastoid outline,the damage of structure in 3D systemis higher than that in cadaver dissection(33.3%>22.2%),but there were no significant difference between them in the proportion of exposure.On the opening of attic,facial recess,facial nerve,the damage and the proportion of the non exposed of cadaver dissection is higher.2There were no significant difference between them in the anatomical structures,levels of pollution,taste,cost and reproducibility(P>0.05),but in the aspect of time,relevance of CT with temporal bone,the similarity,and the force feedback,they had significant differences(P<0.01).Conclusion:3D simulation temporal-bone-system had better training effect in specialized otolaryngologist.It not only to help clinicians better understanding the temporal bone and surrounding structures,but also to emphasize the knowledge of the anatomy in temporal bone. PMID- 29797983 TI - [Utility of inferior turbinate mucosal flap on the repairing defects of palate after tumor excision]. PMID- 29797984 TI - [Application of tragus cartilage in the repair of cerebrospinal otorrhea:a report of 7 cases]. PMID- 29797985 TI - [Childhood nasal lymphoma:two cases report and literature review]. AB - Here we report two childhood lymphoma cases,which present with a nasal cavity associated with obstructive symptoms and intermittence pyrexia.Application of antibiotic can temporarily alleviate these symptoms but it can not cure this disease radically.Computed tomography of nasopharynx showed inferior turbinate hypertrophy and absence of obvious specific manifestation.The examination of blood and marrow cells did not find any abnormity.The precision diagnostic evaluation is biopsy of clinically involved mass.The definitive pathological diagnosis is NK/T cell lymphoma.The two younger children patients have shorter course of disease,lacking typical cinical presentation and auxiliary examination of it.We should be vigilant whether a child having nasal obstruction and pyrexia is probably NK/T cell lymphoma or not. PMID- 29797986 TI - [Four-handed procedure for nasal endoscopic surgery]. AB - Nasal endoscopic surgery was born in the 1950 of the last century in Europe.The original Hopkins and other scholars proposed nose rigid endoscopy to the application of modern advanced "chameleon" nasal endoscopic,roughly experienced 60 years of evolution and development.The development and improvement of endoscopic surgery also in constant evolution,by traditional single hand operation that patients in one hand and holding a mirror,on the other hand took the instrument to attract or punch,to modern groping in the dark hands operation technology,namely assistant control nasal endoscope,surgery were both hands operation,this is called the four hand operation to solve the a lot of nasal endoscopic surgery problem,lay a solid foundation to the continuous expansion of the endoscopic surgery.Nasal endoscopic surgery is the optimal operation mode of the nasal cavity and even the skull base surgery.It is a great breakthrough in the history of endoscopic surgery,and it is also a major improvement in the development of microsurgical technique. PMID- 29797987 TI - [Present situation of laryngotracheal stenosis' diagnosis technology]. AB - Laryngotracheal stenosis is a complex and dangerous disease,which caused by trauma or endotracheal intubation.Accurately and clearly to show the length and area of the airway stenosis,which is of great significance for the correct qualitative and quantitative diagnosis of the disease and the development of the treatment.The relevant inspection has its advantages and disadvantages.How to use inspection accurate and reasonable,there is no unified standard.Therefore,this paper will evaluate the role and significance of different relevant inspection(pulmonary function tests,ultrasound,bronchoscopy,CT,MRI) in the diagnosis of laryngotracheal stenosis,providing reference for laryngeal and tracheal stenosis diagnosis and treatment. PMID- 29797988 TI - [Present state and perspectives of otorhinolaryngology head and neck surgery]. PMID- 29797989 TI - [Age dependent changes in mandarin speech perception in normal hearing people]. AB - Objective:To investigate if and when the mandarin speech perception ability deteriorates with age in adults with audiometrically normal hearing sensitivity.Method:The participant group included 75 normal hearing adults sampled from across the entire range of adulthood, of which there are 20 males and 55 femals. The participants were divided into 5 groups with 15 participants per age group: 20-30 years, 31-40 years, 41-50 years, 51-60 years, and 61-70 years. We applied speech perception test using Mandarin Hearing in Noise Test.Result:The speech perception scores were significantly different among the five groups in 0 dB and -5 dB conditions (P<0.001), but they weren't significantly different among the five groups in quiet, 10 dB and 5 dB (P>0.005).There was a significant negative correlation between speech perception and age in -5 dB conditions.Conclusion:When the background noise becomes more severe even for participants with audiomerically normal hearing, it was shown that speech perception declined with age. PMID- 29797990 TI - [Influence of anti anxiety and anti depression treatment on sudden hearing loss]. AB - Objective:To study the influence of anti-anxiety and anti?depression treatment on patients diagnosed as sudden hearing loss with anxiety and depression symptoms.Method:A prospective and controlled study was carried out. A total number of 248 patients with anxiety and depression symptoms were randomly divided into experimental group or control group by Stochastic tables law. A number of 126 patients in experimental group accepted anti anxiety and anti depression treatment, while 122 patients in control group did not accepted anti anxiety and anti depression treatment. The hearing and tinnitus effects were evaluated.SPSS 13.0 statistical software was used for data processing.Result:According to the results of pure-tone threshold audiometry, in the 126 cases of experimental group, 48 were cured (38.1%), 25 were markedly improved (19.8%), 23 were effective (18.3%), and 30 were invalid (23.8%).The total effective rate was 76.2% (96/126). In the 122 cases of control group, 34 were cured (27.9%),17 were markedly improved (13.9%),18 were effective (14.8%),and 53 were invalid (43.4%).The total effective rate was 56.6%(69/122).The two groups had no significant difference in recovery rates but it showed significant difference in total effective rates. Moreover, the total effective rate of the flat type of sudden hearing loss in experimental group was superior to that in control group, however there was no significant difference in total effective rates of other three types between two groups. The patients who had concomitant symptom of tinnitus in experimental group and control group accounted for 85.7% (108/126) and 84.4%(103/122), respectively. However, no significant difference was found in proportions of patients with tinnitus between the two groups. According to the tinnitus results, in the 108 cases of experimental group, 32 were cured (29.6%),19 were markedly improved (17.6%), 36 were effective (33.3%), and 21 were invalid (19.4%). The total effective rate was 80.6%(87/108). In the 103 cases of control group, 19 were cured (18.4%), 15 were markedly improved (14.6%),22 were effective(21.4%),and 47 were invalid (45.6%).The total effective rate was 54.4% (56/103).The two groups had no significant difference in recovery rates but it showed significant difference in total effective rates. There was no significant difference in total effective rate of the low-middle frequency sudden hearing loss between two groups, but the total effective rates of other three types in experimental group were all higher than those in control group.Conclusion:The total effective rates of hearing and tinnitus can be improved after combination treatment with anti-anxiety and anti-depression in sudden hearing loss patients with anxiety and depression symptoms. Moreover, different types of the hearing curves of sudden deafness have different improvement degrees. PMID- 29797991 TI - [Analysis of virulence genes of Staphylococcus aureus in nasal secretions?of patients with chronic rhinosinusitis]. AB - Objective:To investigate the differences of virulence genes of Staphylococcus aureus in patients with chronic sinusitis with nasal polyps (CRSwNP) and chronic sinusitis without nasal polyps (CRSsNP), and to explore the relationship between different virulence factors and the incidence of sinusitis and nasal polyps.Method:The PCR method was used to detect 17 kinds of virulence genes of Staphylococcus aureus isolated from nasal secretions of 41 strains.Result:1The detection rate of SEB in the experimental group was significantly higher than that in the control group, the detection rate of SEB in the CRSwNP group was higher than that in the CRSsNP group, and the other 5 kinds of enterotoxin genes were not statistically significant between the experimental group and the control group;2Staphylococcus aureus adhesin in the experimental group and the control group were detected, and the detection rate was relative higher in both control and experimental goups. However, the detection rate were not statistically significant between the experimental group and the control group;3The detection rate of HLalpha and HLbeta genes encoding hemolysin was higher in the experimental group and the control group, and there was no significant difference between the 2 groups in the experimental group and the control group.Conclusion:Staphylococcus aureus carrying enterotoxin gene was more likely to cause CRS. The greater the incidence of nasal polyps was found in patients infected by Staphylococcus aureus carrying more enterotoxin gene. PMID- 29797993 TI - [The study of wideband acoustic immittance normative data of young people]. AB - Objective:To explore the normative data of wideband acoustic absorption rate of young people with normal hearing, and the related factors of wideband acoustic immittance.Method:Eighty six cases of young people with normal hearing (43 cases of male, 43 cases of female) were collected in the clinical audiology centers of Beijing Tongren Hospital, Capital University of Medical. The average age is (22.0+/-1.5) years. Pure tone audiometry in the range of 250 to 8 000 Hz in each octave is carried out, and the air conduction thresholds are less than 25 dB HL; 226 Hz tympanometry were type A. For all subjects, the wideband acoustic immittance measurement was conducted at 226-8 000 Hz, and a total of 107 frequency points were carried out.Result:The test results of 172 ears were statistically analyzed.1In the range of 250-8 000 Hz,acoustic absorption rate in the low frequency range increases gradually, and the peak is found in the range of 1 000 to 3 000 Hz;getting along with the increase of frequency and acoustic absorption rate gradually decreases slowly.2The acoustic absorption rate in the range of 4 200-4 900 Hzin female subjects was significantly higher than that in male subjects.3There was no significant relationship between gender, compliance, peak pressure, and width in 226 Hz tympanometry (P=0.319, 0.831, 0.786), however there was a significant relationship between gender and the ear canal volume (P<0.01).4There was no significant relationship between gender and the resonance frequency (P>0.05).5There was a significant correlation between height/weight and ear canal volume (P<0.05), and there was a significant relationship between the ear canal volume and the resonance frequency (P<0.05).Conclusion:The acoustic absorption rate of young people in the low frequency range was lower, then increases gradually, and the peak was found in the range of mid-high frequency. The difference in the wideband absorption rate between genders was significant. The height and weight had influence on the results of wideband acoustic immittance. PMID- 29797992 TI - [Clinical analysis of nose rhabdomyosarcoma]. AB - Objective:To improve the diagnosis of the nose rhabdomyosarcoma.Method:Twenty four patients with nose rhabdomyosarcoma were studied retrospectively.Result:Among 24 patients with nose rhabdomyosarcoma, three patients were in stage I, four patients were in stage II, eleven patients were in stage III, and six patients were in stage IV. Embryonal rhabdomyosarcoma is the commonest in all the pathological types. Most patients need comprehensive therapy, including surgery operation, radiotherapy, and multicycle chemotherapy. Prognosis was poor in most of the cases. The survival rate of one year was 70.8% (17/24), and survival rate of three years was 30.3% (8/24).Conclusion:Different surgical protocols should be adopted for different patients, and postoperative chemoradiotherapy should be adopted for advanced treatment. By means of multidisciplinary collaboration, the patient's survival time would be prolonged. PMID- 29797994 TI - [Three combined imaging studies' diagnostic value for preoperative position of hyperthyroidism]. AB - Objective:To investigatethe diagnostic value of three combined imaging studies' preoperative localization for secondary hyperparathyroidism.Method:This study lies on the retrospective analysis about 72 patients with secondary hyperparathyroidism who had parathyroid gland resection in our hospital from 2010 to 2017. All of 72 cases are examined by color doppler ultrasound,99mTC-MIBI nuclide imaging and magnetic resonance imaging. According to the gold standard pathological diagnosis after surgery, we compute the sensitivity and the specificity of various imaging examination and analyse these statistics by rate card square test with SPSS 19.0 software.Result:The parathyroid gland number of pathological diagnosis is 282. The sensitivities of magnetic resonance imaging, 99mTC-MIBI nuclide imaging, color doppler ultrasound and three combined imaging are 72.70%, 47.52%, 44.33% and 82.27%, respectively. The specificities of the examinations are 78.16%, 91.75%, 95.14% and 67.96%, respectively. The sensitivity of the combined three imaging studies is greater than the sensitivity of each single imaging studies, and there is a statistical significance between them. The specificity of the combined three imaging studies is smaller than the sensitivity of single imaging studies. There is a statistical significance,either.Conclusion:Three combined imaging studies' preoperative localization for secondary hyperparathyroidism has higher diagnostic value for the preoperative localization about secondary hyperparathyroidism. It can be a effective way to SHPT's surgery. PMID- 29797995 TI - [A 212 cases analysis of treatment for traumatic optic neuropathy by nasal endoscopic opticnerve decompression]. AB - Objective:To explore the clinical features and therapeutic efficacy of nasal endoscopic optic nerve decompression for traumatic optic neuropathy (TON)treatment.Method:Two hundred and twelve cases (217 eyes) with TON were retrospectively analyzed in our study, who were treated with nasal endoscopic optic nerve decompression in our institution from 1999 to 2016. chi 2 -test was used to explore the potential prognostic factors on visual acuity.Result:All patients were followed up from 6 months to 2 years postoperatively, and the effective rate was 54.38%(118/217).In the 166 eyes with no light perception (NLP), the effective rate was 46.39% (77/166), while in the 51 eyes with light perception (LP), the effective rate was 80.39% (41/51).The therapeutic efficacy of patients with LP or above LP was better than that of NLP, and the difference was statistically significant(chi 2=18.186, P< 0.01).Moreover, the therapeutic efficacy of patients without an optic canal fracture was better than that with an optic canal fracture,and the difference had statistical significance (chi 2=10.096, P<0.01).Conclusion:The efficacy of nasal endoscopic optic nerve decompression on TON was positive, and even for the patients with NLP or a long history also should have a try. PMID- 29797996 TI - [Clinical study of chondrosarcoma in the jugular foramen]. AB - Objective:To explore the diagnosis and surgical treatment of chondrosarcoma in the jugular foramen (JF).Method:This study lies on the retrospective analysis about 72 patients with secondary hyperparathyroidism who had parathyroid gland resection in our hospital from 2010 to 2017. All of 72 cases are examined by color doppler ultrasound,99mTC-MIBI nuclide imaging and magnetic resonance imaging. According to the gold standard pathological diagnosis after surgery, we compute the sensitivity and the specificity of various imaging examination and analyse these statistics by rate card square test with SPSS 19.0 software.Result:The main complaints in the patients included hearing loss, facial palsy and tinnitus. All patients achieved total removal with IFTA-A as initial treatment. Three cases underwent facial nerve grafting and preoperative cranial nerve dysfunction didn't aggravate in our cases. No recurrence or major complication has been identified till the latest follow up.Conclusion:Chondrosarcoma in the JF is a rare entity. Misdiagnosis frequently occurs in clinical practice. Special attention should be paid to the clinical characteristics and radiological findings when encounters a lesion in the jugular foramen. It is believed that the complete resection of the tumor should be the initial choice for patients with chondrosarcoma in the JF. PMID- 29797997 TI - [Study on the incidence and characteristics of carotid canal dehiscence with high resolution CT]. AB - Objective:To discuss the total incidence and characteristics of carotid canal dehiscence in Chinese adults with high resolution CT. At the same time, it provide basic data for otology clinical medical personnel to further understand the anatomical structure of ear and carry out auditory surgery.Method:Temporal bone HRCT images of 643 consecutive subjects who underwent CT scanner were analyzed retrospectively. The coronal, sagittal, and oblique sagittal plane were reconstructioned for some suspected subjects. Contrast the incidence of carotid canal dehiscence in different sex, bilateral and age groups.Result:In 643 patients, 43 cases found the carotid canal dehiscence, and the total incidence of carotid canal dehiscence was 6.7%.The incidence of carotid canal dehiscence for male and female were 5.9%(16/269)and 7.2%(27/374)(P > 0.05),and there was no statistically significant difference in the incidence of carotid canal dehiscence between sexes. The incidence of carotid canal dehiscence for age 40-59 was much higher than those of other age groups (P< 0.05),however, there was no significant difference between groups of age 20-39 and >=60(P> 0.05).The location of the carotid canal dehiscence in 43 cases was located in the mesotympanum near the Eustachian tube orifice. Carotid artery tube ruptures are mostly small defects, but 11 cases with major defect.Conclusion:The toatal incidence of carotid canal dehiscence is 6.7% in Chinese adults (males: 5.9%,females: 7.2%), especially high incidence at group of age 40-59 (10.7%). Carotid canal dehiscence can be diagnosed accurately by HRCT and multiplanar reconstruction. PMID- 29797998 TI - [The relation between cochlear distortion products and frequency tuning characteristics revealed by laser interferometery]. AB - Objective:To explore the relation between distortion products and frequency tuning charateristics in cochlear basilar membrane.Method:Time variances curves of distortion products and frequency tuning curves of basilar membrane response were measured by laser interferometery in situ guinea pig cochlea.Result:Response sensitivity and tuning sharpness of basilar membrane response decreased with distortion product amplitude and become most low and flat when distortion products disappeared.Conclusion:Distortion products in cochlea are related with hearing sensitivity and frequency tuning. They are indicator whether function of cochlear hearing sensitivity enhancing and frequency tuning sharpening is still at work. PMID- 29797999 TI - [Expression of eosinophils and IL-33 levels in peripheral blood of patients with allergic rhinitis]. AB - Objective:To investigate the relationship between the count of eosinophils(EOS) in peripheral blood and the serum levels of IL-33, and to discuss the relations among serum levels of IL-33, the count of EOS, visual analog scale (VAS) in different groups.Method:According to different treatments, the patients are divided into three groups: the untreated allergic rhinitis (AR) group (group A), the AR group who had been treated subcutaneous imunotherapy (SCIT) for at least a year (group B) and the AR complicated with allergic asthma group who had been treated subcutaneous imunotherapy (SCIT) for at least a year (gourp C). All subjects were conducted blood cell analysis, and EOS were counted. The serum levels of IL-33 were measured by enzyme linked immune (ELISA), and the obtained date were analysed by GraphPad.Prism 5.0 and SPSS 22.0.AR patients were asked to fill out VAS and were assessed nasal symptoms.Result:The serum levels of IL-33 in the group A were higher than that in other subjects (P<0.05).The serum levels of IL-33 in the group B showed no significant difference between the group B and the group C (P> 0.05).The serum levels of IL-33 in the group B were higher than that in the control group (P<0.05).The serum levels of IL-33 in the group C were higher than that in the control group (P<0.05).The count of EOS in the group A were higher than that in other subjects, and there is no difference between with each other (P> 0.05).The VAS in the group A were higher than that in the group B (P<0.05) and there is no significant difference between the group A and the group C (P<0.05).There is no difference between the group B and the group C(P<0.05).After at least one-year SCIT, the symptoms of AR patients were obviously relieved, such as consciously rhinobyon, rhinorrhea, sneezing and so on. Spearman test showed the serum levels of IL-33 in the AR patients has a weak correlation with the count of eosinophils (P> 0.05, r=0.287).Conclusion:SCIT is an effective treatment for AR patients. role on AR, which can alleviate the symptoms of patients, also can reduce the levels of IL-33 and the count of EOS in peripheral blood. PMID- 29798000 TI - [The clinicopathological associations between TGF-beta1 and papillary thyroid carcinoma: a Meta-analysis.] AB - Objective:To comprehensively evaluate the association between the positive expression rate of transforming growth factor beta 1 (TGF-beta1) and papillary thyroid carcinoma (PTC) by using Meta-analysis.Method:Search the CNKI, Wan fang, VIP and PubMed database for accumulating papers studying on the relationship between the positive expression of TGF-beta1 and PTC in Chinese and English. Revman 5.3 was used to analyze the included trials.Result:A total of 6 studies comprising 617 samples was included in the meta-analysis. The TGF-beta1 were found in 243 patients (64.63%) of 376 PTC patients, and the total positive expression rate is 46.19%. Performing the subgroup analysis according to age, gender, lymphatic metastasis and TNM, the results showed that there was a significant association between the positive expression rate of TGF-beta1 and lymphatic metastasis (OR=5.44, 95%CI3.31-8.93,P <0.000 01).Conclusion:This meta analysis confirmed significant associations between the expression of TGF-beta1 and PTC with lymph node metastasis. TGF-beta1 may be used as a predictive factor for prognosis of PTC with lymph node metastasis. PMID- 29798002 TI - [Autologous external jugular vein grafting to reconstruct segmental common carotid-internal carotid artery: one case report]. AB - We reported a case of carotid body tumor (Shamblin classification, typeIII) patient on whom the tumor was tightly adhered to the carotid bifurcation and the carotid artery broke during the surgery,then autologous external jugular vein was employed to reconstruct the segmental defect of common-internal carotid artery after the tumor and involved common-internal carotid artery was resected. The patient felt no complaint during the two-year follow-up. Duplex scan demonstrated the patency of transplanted external jugular vein was a good graft without formation of aneurysm. At the time of 2 years after surgery, the transplanted vein arterialized without obvious stricture. This case implies that the external jugular vein grafting is a candidate for reconstruction of segmental carotid artery. PMID- 29798001 TI - [A Meta-analysis of comparing effectiveness and safety between minimally invasive video-assisted thyroidectomy and conventional thyroidectomy in the treatment of papillary thyroid carcinoma without lymph node metastasis]. AB - Objective:To compare the effectiveness and safety between minimally invasive video-assisted thyroidectomy (MIVAT) and conventional thyroidectomy (CT) in the treatment of papillary thyroid carcinoma without lymph node metastasis, providing clinicians using video-assisted way to treat thyroid papillary carcinoma with a more reasonable basis.Method:According to the including and excluding criterion,we searched the published articles which compare the effectiveness of MIVAT and CT curing PTC in randomized controlled clinical trials. The searching time was from January 2011 to December 2016, and the data was analyzed by using revman 5.3 software.Result:Twelve articles involving 1 080 cases were included,and there were 514 cases in the MIVAT group and 566 cases in the CT group. The results of meta?analysis showed that: the operation time of MIVAT group is longer than that of CT group (MD=17.19, 95%CI12.43-21.96, P<0.05); however the VAS point of MIVAT group is less than that of CT group in twenty?four hours after surgery (MD-1.07, 95%CI-1.61--0.53, P<0.05). There is no significant difference in the incidences of transient recurrent laryngeal nerve injury(OR=2.21,95%CI0.9-5.07,P>0.05),transient hypoparathyroidism (OR=0.78, 95%CI0.48-1.28, P>0.05), serum thyroglobulin after five years followed up (MD 0.05, 95%CI -0.25-0.16?, P>0.05), number of retrieved central lymph nodes (MD= 0.36, 95%CI -0.72-0.01, P>0.05) and number of retrieved central positive lymph nodes (MD=-0.15, 95%CI -0.45-0.16, P>0.05).Conclusion:Using MIVAT treating papillary thyroid carcinoma (without lymph node metastasis) is safe when its indications are strictly controlled. PMID- 29798003 TI - [First branchial cleft cyst in nasopharynx: a case report]. AB - We report a rare case of first branchial cleft cyst arising from the nasopharynx. A 47-year old woman with a six-month-history of right ear stuffy and hearing loss was studied. Electronic nasopharyngeal examination revealed a mass in the nasopharynx of this case. The tumor was removed endoscopically with endonasal approach. Postoperative pathological examination indicated that it was branchial cleft cyst. PMID- 29798004 TI - [Oropharyngeal alveolar soft tissue sarcoma: a case report]. AB - Alveolar soft tissue sarcoma(ASPS) is a rare kind of highly malignant tumors. It has the characteristics of young onset age, early metastasis, low five-year survival rate and poor long-term prognosis. ASPS often occur in the deep soft tissues of limbs, while less occur in the head and neck. Articles about ASPS most dominated by cases report, and so far no report seen in oropharyngeal ASPS. This paper reported one case of oropharyngeal ASPS, and reviewed the literature and discussed on its clinical manifestations, imaging features, histological features, diagnosis, therapy and prognosis. PMID- 29798005 TI - [Research progress of vascular pulsatile tinnitus]. AB - Pulsatile tinnitus (PT) is relatively rare, which accounts for approximately 4% of patients with tinnitus. It originates from mostly vascular structures within the cranial cavity, head and neck region or thoracic cavity, and is transmitted to the cochlear by bony or vascular structures and the blood flow, stimulating patient's hearing. It can be the patient's subjective feelings, there can be objective performance.Vascular PT is more common than non-vascular PT. Vascular PT can be further classified by vessel of origin as arterial and venous ones, and the latter is more commonly seen clinically.It's rhythm is synchronous with patients' pulse, and its tinnitus frequency is less than 600 Hz. The cause of pulsatile tinnitus is complex and diverse, and 56 cases are reported in the literature. Objective tinnitus or somatosensory, associated with tympanic membrane myoclonus, ear blood flow changes adjacent to blood vessels and other in vivo factors. While subjective tinnitus lacks a clear source of the body. PT's pathogenesis has not been fully understood yet, so intensive study targeting PT is of great importance. This review focuses on the pathophysiological mechanisms,etiology,clinical manifestation, diagnosis and progress of treatment of vascular PT. PMID- 29798007 TI - [Value research of chemokines in eosinophilic chronic rhinosinusitis with nasal polyps]. AB - Eosinophilic chronic rhinosinusitis with nasal polyps is an immune inflammatory disease with high incidence rate and complicated mechanism.The target of treatment is still unclear.Chemokines, as an important component of immune inflammatory response, playing an important role in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps, and being one of the focuses of the researches.It is discussed in this paper that the role and possible intervention measures of the chemokines combined their specific receptor in the occurrence and development in the eosinophilic chronic rhinosinusitis with nasal polyps, trying to find new therapeutic targets and provide new ideas for priceseand personalized treatment of the disease. PMID- 29798006 TI - [The influence of air pollution on the pathogenesis of allergic rhinitis]. AB - The incidence of allergic rhinitis is increasing with the development of the city and industrial mechanization. The human living environment changes greatly, and air quality has deteriorated sharply, leading to a series of diseases (such as allergic rhinitis, asthma, allergic conjunctivitis). Although the pathogenesis of allergic rhinitis is relatively complex, however it is confirmed that its pathogenesis has a relation with the air pollution. Allergic rhinitis bring great inconvenience to patients in daily life. Thus, it is very important to study the process of air pollution causing allergic rhinitis. This article mainly expounded the prevalence of allergic rhinitis, outdoor air pollution (SO2, O3, NO2, fine particulate matter, greenhouse gases) and indoor air pollution (volatile organic compounds, ETS). Additionally, the mechanism of allergic rhinitis caused by air pollution was further explored, and how to avoid the happening of the disease was discussed. PMID- 29798008 TI - [Contemporary issues in the recording of vestibular evoked myogenic potentials]. PMID- 29798009 TI - [Progress in the study of central auditory processing disorders]. AB - Summary With the development of artifical ossicular and cochlear implant,the treatment of refractory hearing loss acquire significant breakthrough,thus central auditory processing disorders are becoming the major cause of refractory hearing loss.In this paper,research progress of central auditory processing disorders in clinical and fundamental are reviewed. PMID- 29798010 TI - [Application of objective audiological tests in bilateral tinnitus patients with normal hearing capability]. AB - Objective:To analyze the relationship of tinnitus and early stage damage of cochlear, to explore the clinical applied value of distortion product otoacoustic emission(DPOAE) and auditory brainstem response(ABR) in the bilateral tinnitus patients with normal hearing capability. Method:There are 30 cases(60 ears) in the tinnitus group with bilateral tinnitus patients with normal hearing capability, and there are 30 cases(60 ears) in the control group without tinnitus of normal hearing capability. The two groups both test the DPOAE and ABR,and compare the results of the DPOAE and ABR. Result:The passing rate of DPOAE in all frequencies was 100% in the control group,42.67% in the tinnitus group. Significant differences existed between the two groups(P<0.05).The DPOAE could be checked out at all frequencies under 2 kHz except 0.75 kHz in the tinnitus group, and the passing rates of DPOAE were significantly lower than those in control group(P<0.05).There were 3 cases could not be checked out at 0.75 kHz frequency, but there were no significant difference(P>0.05).The DPOAE amplitudes at frequencies of 3 to 8 kHz in tinnitus ears were significantly lower than those in nontinnitus ears(the P value were 0.011,0.013,0.008,0.027 ).Wave I,III and Vcould be detected in all ears tested at 80 dB nHL. The latencies of WaveIin tinnitus group were obviously prolonged.The latencies of Wave III and V in tinnitus group were also prolonged, but there was no significant difference(P>0.05).The interval between waves Iand III,waves III and Vand wavesIand V showed no difference. Conclusion:The maybe cochlear early injury in fractional bilateral tinnitus patients with normal hearing capability, DPOAE and ABR can act as an objective method for diagnosing peripheral tinnitus. PMID- 29798011 TI - [The application of mandarin acceptable noise level and COS in hearing aid fitting for presbyacusis]. AB - Objective:The purpose of this study was to inquiry into the application of mandarin acceptable noise level(M-ANL) and client oriented scale of improvement in evaluation of hearing aid fitting for presbyacusis. Method:Thirty-two adults with presbycusis who used the hearing aid for the first time were selected for the study. M-ANL tests were done prior to the hearing aid fitting. Six weeks later, these patients were asked to fill in questionnaire of client oriented scale of improvement (COSI).The subjects were divided into 3 groups according to the time of hearing aid using in their daily lives: less than one hour per day, 1 to 4 hours per day and more than 4 hours per day. The relativity of M-ANL and the score of COSI were compared. Result:1There were significant differences of the M ANL among 3 groups(P<0.05); 2The scores of COSI of group 1(less than one hour per day) was lower than group 2(1 to 4 hours per day), while there were no significant differences between the scores of group 2(1 to 4 hours per day) and group 3(more than 4 hours per day); 3There was good correlation between the score of M-ANL and COSI. Conclusion:M-ANL can forecast the satisfaction of hearing aids fitting. And COSI can play an effective role in outcome measurement. PMID- 29798012 TI - [Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard]. AB - Objective:To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method:Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result:Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post hoc tests showed no significant effect between individual regions. Conclusion:Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. PMID- 29798013 TI - [Relationship and significance among IL-6,PI3K/Akt and GSK 3beta in chronic rhinosinusitis]. AB - Objective:To explore the relationship and significance among the expressions of cytokines IL-6,PI3K/Akt signaling transduction pathway, and GSK3beta in chronic rhinosinusitis.Method:The proteins for IL-6,PI3K,Akt,GSK3beta were assayed by Western blot, and mRNAs of cytokines IL-6,IL-6 receptor were measured by real time quantitative polymerase chain reaction(qPCR) in nasal tissue from the patients with chronic rhinosinusitis with nasal polyps(CRSwNP),chronic rhinosinusitis without nasal polyps(CRSsNP) and control subjects. Result:IL 6,PI3K,Akt,GSK3beta proteins in CRS were higher than those in the control subjects, the differences were statistically significant(P<0.05). There was no significant difference between the groups of CRSsNP and CRSwNP. There were significant differences of cytokines IL-6 mRNA expression between CRSsNP, CRSwNP and control group(P<0.05).IL-6 exists in two forms glycosylated(55 kd) and non glycosylated(25 kd) in CRS. CRSsNP group mainly glycosylated (glycosylated and non-glycosylated protein expression ratio is about 2.4:1),CRSwNP group mainly non glycosylated(glycosylated and non-glycosylated protein expression ratio values about 0.4:1).There was a positive correlation trend among the expressions of IL 6,PI3K,Akt and GSK3beta in CRS. Conclusion:The abnormal expressions of IL 6,PI3K,Akt and GSK3beta in the nasal mucosa of CRS may play a pro-inflammatory role in the occurrence and development of CRS. The glycosylated IL-6 and the non glycosylated IL-6 may be both involved in the inflammation of CRS. PMID- 29798014 TI - [Analysis of BPPV in patients with bone mineral density results]. AB - Objective:Analyze BPPV in patients with ultrasonic bone mineral density to investigate the relationship between the BPPV and bone density. Method:A total of 88 included subjects were selected from patients admitted to the Otolaryngological Department of Renhe Hospital, Beijing. Meanwhile, 76 healthy persons were included as control. The control group had similar age and gender distributions to the test group, and all healthy subjects had no history of vertigo in recent one year. Both groups underwent regular otolaryngological examinations, videonystagmography(VNG),ultrasound bone densitometer test. According to gender, age, listening to group. Result:1Bone density of the test group was significantly lower than the control group(-2.010+/-1.658 vs 0.3605+/ 0.875),the difference was statistically significant(P<0.01);2Incidence rates of bone mass loss(35 in 88,39.77%)and osteoporosis(26 in 88, 29.55%)bone mineral density decreased incidence of 69.32%, in the test group was significantly higher than that in the control group(bone mass loss, 13 in 76, 17.10%; osteoporosis 6 in 76,7.89%), bone mineral density decreased incidence of 25.00%,the difference was statistically significant(P<0.01);3The test group and control group according to different age groups, the test group all ages bone density T values significantly lower than the control group(P<0.01),the difference was statistically significant. In the age groups, the incidence of bone loss was higher in the test group than that in the control group, the difference was statistically significant(P<0.01).4In the gender group, bone density of the test group women were significantly lower than the control group, the difference was statistically significant(P<0.05); especially after the age of 60.5In the test group, 27 cases of bone mineral density is normal, with normal hearing 19 cases (70.37%), hearing loss 8 cases(29.63%);61 cases of bone loss, including normal hearing 48 cases (78.69%),hearing loss 13 cases (21.31%). The difference between hearing loss and bone loss had no statistical significance(P>0.05).6The logistic regression results showed that the prompt Higher bone mineral density T value was BPPV protection factors, OR=0.686,(P<0.01,95%CI: 1.32-5.85). Conclusion:BPPV in patients with bone mineral density value is lower than the normal control group, there is a higher incidence of bone loss, at the same time, along with the age increasing on the rise, especially women. PMID- 29798015 TI - [Study on the influence of laryngeal lesions on the prognosis of pneumomediastinum in dermatomyositis]. AB - Objective:To investigate the influence of laryngeal lesions on the prognosis of pneumomediastinum in patients with dermotomyositis(DM). Method:The clinical data of patients with DM were retrospectively analyzed. Hoarseness, laryngeal lesions and pneumomediastinum in patients with DM were analyzed to evaluate the influence of laryngeal lesions and hoarseness on the prognoses and diagnosis of pneumomediastinum in patients with DM. Result:Forty-two patients with a diagnosis of DM were included in the study.Twenty of all the patients were diagnosed of interstitial lung disease(ILD) with the incidence of 47.6%. Four of the patients displayed hoarseness with the incidence of 9.5%. Three cases were complicated by pneumomediastinum with the incidence of 7.1%. All patients have normal vocal cord movement. One of the 4 patients with hoarseness showed congestion of her vocal folds, and the other 3 patients showed white change on both of the vocal folds. All the 3 patients with white change on both vocal folds complicated by pneumomediastinum and died on respiratory failure. There were statistical differences(P<0.01) on the prognosis and occurrence of pneumomediastinum between patients with or without hoarseness and laryngeal lesions. Conclusion:Hoarseness and laryngeal lesions may associate with poor prognosis and occurrence of pneumomediastinum in DM. PMID- 29798016 TI - [Effect of tympanostomy tube insertion with adenoidectomy for children with recurrent otitis media with effusion]. AB - Objective:To observe the clinical effect of tympanostomy tube insertion with adenoidectomy for children with recurrent otitis media with effusion. Method:One hundred and twenty-six cases of children with recurrent otitis media were randomly divided into observation group and control group(63 in each group), subsequently compared the therapeutic effect of the two groups which observation group had tympanostomy tube insertion with adenoidectomy and the other group had only tympanostomy tube insertion. Result:In terms of the total effective rate,observation group and control group were 96.82% and 76.19% respectively, the difference had statistical significant(P<0.05);compared to control group, the recurrent rate of observation group after treatment was extremely lower, the same as middle ear cavity effusion time, which both had statistical significance (P<0.05); the complete healing time of two groups had no statistical significance(P>0.05). Conclusion:Tympanostomy tube insertion with adenoidectomy has significant treatment effect for children with recurrent otitis media with effusion, it could reduce the recurrent rate after surgery and shorten the time of middle ear cavity effusion. PMID- 29798017 TI - [PM2.5 and polluted gas exposure induced acute injury in rats'larynx membrane]. AB - Objective:To study acute injury of rat's larynx membrane which were exposured to PM2.5 and polluted gas in serious air pollution. Method:Rats were divided into 3 groups of 5 animals each, the normal control group, gas exposured group, PM2.5 +gas exposured group. The control group served as the normal healthy control, rats of the gas exposured group had been exposured polluted gas in the A cabin, rats of PM2.5 +gas exposured group had been exposured PM2.5 and polluted gas in the B cabin. The total exposure time was six days. We collected specimen from 3 groups immediately after exposure. Histopathological changes in the rat's larynx membrane were assessed using hematoxylin and eosin staining(HE), the expression of IL-1beta in laryngeal mucous membrane were assessed using immunohistochemical staining(IHC), and the ultrastructure changes were observed under TEM. Result:HE staining showed the rat's laryngeal mucosa cells in the normal control group had no obvious abnormalities, laryngeal mucosa of rats in the two experimental group had different degrees of cell proliferation, cell polarity change, etc. IHC staining showed that there's no obvious expression of IL-1beta in laryngeal mucous membrane in the normal control group, and positive expression in the two experimental group. TEM showed the control group had no obvious abnormalities, the laryngeal mucosa cells in the two groups of experimental groups had been found irregular nucleus and damaged mitochondria. Conclusion:Exposed to PM2.5 and polluted gas in severe atmospheric pollution 6 days, the acute damage in rats laryngeal mucosa can be observed. PMID- 29798018 TI - [Effect of hydrogen peroxide on the lateral line hair cell regeneration of zebrafish]. AB - Objective:To investigate effect of hydrogen peroxide (H2O2) in the lateral line hair cell growth and regeneration after damage on zebrafish. Method:Select 5 dpf zebrafish, each group of 10, randomly divided into A control group: the system of water culture. B H2O2 group: 10 MUmol/L, 20 MUmol/L H2O2 solution to replace three times a day. C neomycin group: treatment with system water after 1 h culture by 200 MUmol/L neomycin. D neomycin + H2O2 group: 20 MUmol/L H2O2 solution to replace three times a day after 200 MUmol/L neomycin treatment for 1 h. E cisplatin group: treatment with system water after 3 h culture by 1 000 MUmol/L cisplatin. F cisplatin + H2O2 group: 20 MUmol/L H2O2 solution to replace three times a day after 1 000 MUmol/L cisplatin treatment for 3 h. Each group in H2O2 treatment for 0 h, 24 h, 48 h was marked their hair cells by immunofluorescence method and count the P1, P7, P8 neuromasts under the fluorescence microscope. Repeat 3 times. Result:The number of hair cells on P1, P7, P8 three neuramasts among 5 to 7 dpf zebrafish were 9.364+/ 0.901(n=11),9.645+/-0.598(n=15),9.922+/-0.862(n=13), no obvious difference (P>0.05); 10MUmol/L, 20MUmol/L H2O2 treated zebrafish for 48 h, the numbers were 11.540+/-0.741,11.905+/-0.607,compaired with the control group(10.841+/-0.389), P<0.05; neomycin+ H2O2 48 h and neomycin 48 h respectively were 10.600+/ 0.689,8.767+/-0.603, P<0.01; cisplatin+ H2O2 48 h and cisplatin 48 h were 5.967+/ 1.086,5.633+/-1.548, P>0.05. Conclusion:20 MUmol/L H2O2 promotes the development of lateral line hair cells of zebrafish; H2O2 promotes the regeneration of the lateral line hair cells after injury of neomycin, but not cisplatin. PMID- 29798019 TI - [Infection of chronic otitis media with Acinetobacter:6 cases report]. AB - Objective:To investigate the clinical characteristics, diagnostic methods and prognosis of patients with chronic otitis media with Acinetobacter infection. Method:Retrospective analysis of clinical data of 6 cases of chronic otitis media complicated with Acinetobacter infection. Including history, clinical manifestations, laboratory examination, audiology, inner ear, CT, MRI imaging characteristics, treatment and prognosis of etc. to summarize the clinical characteristics, diagnosis and treatment of chronic otitis media with Acinetobacter infection. Result:The age was between 17 years old and 61 years old (Median age 30 years) .Two of them was male and 4 were female. Four cases were had underlying diseases. Five cases with main symptom of cholesteatoma, 1 case with earache symptoms, and 1 case with facial paralysis symptoms. Four cases had vary degrees of physical decline and destruction of bone. After surgery treatment, five patients improved ear pus, among 3 cases was cured, 2 cases of recurrence. Conclusion:Chronic otitis media with Acinetobacter infection occurs in the patient with elderly, poor physical constitution. However, the recurrence rate of conventional treatment is higher. The disease has high misdiagnosis rate. Operation combined with sensitive antibiotic therapy is a radical cure method. PMID- 29798020 TI - [Clinical analysis of 872 cases with epistaxis and application of hypothermy plasma]. AB - Objective:To explore the best method to cure nasal bleeding based upon the patients age, complications, bleeding reasons, bleeding site. Method:A retrospective study of 872 patients with a diagnosis of nasal bleeding in our hospital.The location of bleeding was determined according to the specialized examination,nasal endoscopy and surgical exploration, and the reasons of epistaxis and its characteristics were also analyzed according to the history, biochemical examination, physical examination, imaging examination. Result:The case number significantly increased with age. The main reason for nasal bleeding were deviation of nasal septum, hypertension, taking anticoagulant drugs, vascular tumor and diabetes mellitus. The main bleeding sites are the unknown parts, the olfactory cleft, little area, meatus nasi inferior, basis nasi and spur. The main methods for the treatment of nosebleed are endoscopic surgery and nasal packing. Conclusion:Because of the different nasal bleeding reasons and bleeding sites among individuals, individualized treatment methods are required to cure nasal bleeding. With the advantages of the clear vision, accurate location, fast stop bleeding,endoscopic method has become the first treatment for nosebleed. PMID- 29798021 TI - [Expression and clinical significance of HIF-1alpha in laryngeal carcinoma]. AB - Objective:To investigate the expression and clinical significance of HIF-1alpha in laryngeal carcinoma(LC). Method:Databases including PubMed, EMbase, Web of Science, VIP, CNKI and Wan-Fang Data were searched from 2000.1 to 2015.12, and all relevant references were also retrieved to collect relevant case-control studies. The included studies were screened according to the exclusion criteria. Then the meta-analysis was conducted by RevMan 5.3 software. Result:A total of 5 case-control studies involving 202 LC tissues and 75 normal laryngeal tissues were included. The results of the meta-analyses showed that, as for the positive rate of HIF-1alpha expression, it was higher in LC tissues than that in normal esophageal tissues [OR=22.4,95%CI (9.79,51.25),P<0.01], in LC tissues with lymph node metastasis than in that without lymph node metastasis [OR=7.10,95%CI (3.10, 16.30), P<0.01], in moderate and low differentiated LC tissues than those in high differentiated LC tissues[OR=4.40, 95%CI (2.28, 8.49), P<0.01].The expression of HIF-1alpha in clinical stage III-IV was significantly higher than that in clinical stage I-II[OR=5.89, 95%CI (2.44, 14.24), P<0.01]. Conclusion:The present limited evidence shows that the HIF-1alpha expression is associated with LC, lymph node metastasis, degree of cell differentiation and clinical stage of LC, indicating that LC may take a role in the whole course of carcinogenesis of LC. Further well-designed and high quality case-control studies are needed to prove the results. PMID- 29798022 TI - [Diagnosis and surgical reconstruction results for 14 cases of patients with congenital ossicular chain malformation]. AB - Objective:To investigate the diagnosis of common congenital ossicular chain malformation and the efficacy of ossicular chain reconstruction. Method:Fourteen cases with 15 ears of congenital ossicular chain malformation were included, consisting of 10 cases unilateral conductive hearing loss(10 ears), 1 case bilateral conductive hearing loss (2 ears) and 3 cases unilateral mixed hearing loss with significant conductive hearing loss(3 ears). Tympanoplasty was proceed on all 15 ears, 1 ear was proceed by loosen the cartilage fixation of ossicular chain and tympanic cavity wall. Fourteen ears were proceed with ossicular chain reconstruction, including 3 ears with TORP,10 ears with PORP and 1 ear with artificial stapes operation. The efficacy was measured by comparing the values of air bone gap(ABG) before and after the operation. Result:The average ABG of pre operation was 39.9 dB, the ABG for 3 week and 6 to 8 months after operation were 22.3 dB and 19.6 dB, which were 17.6 dB and 20.3 dB improve respectively(t=22.10, P<0.01 and t=12.813,P<0.01). Conclusion:Operation is the first choice for those conductive hearing loss causing by simple congenital ossicular chain malformation, relevant ossicular chain reconstruction due to particular situation of the surgery can significantly improve hearing. PMID- 29798023 TI - [The diagnosis and treatment analysis of compound-benign paroxysmal positional vertigo in 38 cases]. PMID- 29798024 TI - [A case of nasal big angiosarcoma]. AB - Angiosarcoma also called malignant hemangioendothelioma, caused by vascular endothelial cells or in the direction of vascular endothelial cell differertiation of mesenchymal malignant tumor, is a rare tumor found in clinical, can be in any place of the body, such as head and neck, skin and tissue, breast, bone, liver and other organs and so on, also in the nose, and sinuses rich blood vessels. But this tumor has a low incidence in the nose. Because the nose and sinuses location is hidden, the patient often with nasal bleeding, stuffy nose, headache and so on. With the increase of tumor involvement, the patient can appears the symptoms of corresponding adjacent tissue. Therefore this tumor is difficult to be early detected timely. Early complete surgical excision and supplemented by radiotherapy are preferred methods as the treatments of the nasal and sinuses angiosarcoma without distant metastase. PMID- 29798025 TI - [Primary neuroendocrine carcinoma of the tonsil: two case reports and review of the literature]. AB - Neuroendocrine carcinoma(NEC) of the tonsil is extremely rare. Only a few cases of this tumor have been reported so far. In this article, we described two patients presented with abnormal sensation of throat or throat pain. The pathological examination were NEC. With review of the literatures, the clinical characteristics were summarized and therapeutic strategies were discussed. PMID- 29798026 TI - [Reconstruction of congenital non-syndromic middle ear malformations]. PMID- 29798027 TI - [Clinical analysis of benign paroxysmal positional vertigowith multiple canal involvement]. AB - Objective:To compare the clinical features and outcomes between patients with multi-canal benign paroxysmal positional vertigo(BPPV) and single-canal BPPV.Method:Five-hundred and seventy-eight patients with BPPV were retrospectively analyzed and divided into three groups: single-canal BPPV(526 cases),multi-canal BPPV in unilateral ear(11 cases) and multi-canal BPPV in both ears(41 cases).All patients were diagnosed by using the Dix-Hallpike test or roll test and treated with the canalith repositioning procedure.The following factors,including aetiology,age,sex,response to treatment and recurrence,were compared among the three groups.Results:1Greater percentage of idiopathic cases were identified in single-canal(66.2%:48.2%,P<0.01).Traumatic origin and prior history of BPPV were more common in bilateral multi-canal(41.6%:9.2%,P<0.05)and unilateral multi-canal (36.2%:0,P<0.01)respectively.2The recurrence rate was higher in multi-canal BPPV(40.4%:14.3%,P<0.01).Conclusion:Idiopathic BPPV is more common in single-canal BPPV.Potential causes may be identified in multi-canal BPPV.However,over 90% of the patients with single-canal and multi-canal BPPV are cured. PMID- 29798028 TI - [The normative values of vestibular evoked myogenic potentialin different age groups]. AB - Objective:To obtain the normative values of vestibular evoked myogenic potential(VEMP),i.e.the threshold,latency,latency-interval,amplitude of healthy population in Tianjin medical university General hospital.These values will help clinical diagnosis.Method:Seventy-five healthy individuals (39 males and 36 females,age from 21 to 70 years)were enrolled in this study.They were divided into 3 groups according to age:group 1(21-30 years),group 2(>30-50 years),group 3(>50-70 years).oVEMP and cVEMP were performed and the normative values were obtained.SPSS 19.0 was used to analyze the data.Result:The response rate was 77.3% and 85.3% of oVEMP and cVEMP respectively in all subjects.The values of oVEMP:in group 1 response rate was 100%,amplitude was(8.29+/-1.25)MUV and threshold value was(83.65+/-4.10) dBnHL.In group 2 response rate was 85.4%,amplitude was(6.32+/-1.21)MUV and threshold value was(89.24+/-4.18) dBnHL.In group 3 response rate was 46%,amplitude was(4.26+/-1.20) MUV,threshold value was(95.13+/-4.21) dBnHL.The values of cVEMP: in group 1 response rate was 100%,amplitude was(108.87+/-19.10)MUV and threshold value was(84.54+/-4.35) dBnHL.In group 2 response rate was 83.3%,amplitude was(84.10+/-20.02)MUV and threshold value was (90.33+/-4.29)dBnHL.In group 3 response rate was 72.0%,amplitude was(64.18+/-19.22)MUV and threshold value was (95.19+/ 4.30)dBnHL.The statistical analysis show significant difference in oVEMP/cVEMP response rate,threshold and amplitude among different age-groups(P<0.05).No significant difference was found in N1,P1 latency and latency-interval among different age-groups(P>0.05).Conclusion:The normative values of VEMP of healthy population in Tianjin medical university General hospital were obtained in this research.These VEMP data were used for the diagnosis of related diseases. PMID- 29798029 TI - [The clinical significance of PRL-3,VEGF expression in sinonasalsquamous cell carcinoma]. AB - Objective:To analyze the clinical significance of phosphatase of regenerating liver-3(PRL-3) and vascular endothelial growth factor(VEGF)expression in sinonasal squamous cell carcinomas.Method:We use immunohistochemical analysis and RT-PCR to detecte the expression of PRL-3 and VEGF protein in 62 cases of sinonasal squamous carcinoma tissues(SNSCC),30 cases of nasal polyps(NP),and 25 cases of normal nasal mucosa(NM).Result:1The expression of PRL-3 and VEGF in sinonasal squamous cell carcinoma tissues were statistically higher than in nasal polyps and normal nasal mucosa tissues (P<0.05).2The expression of PRL-3 and VEGF were not correlated with patient's age or gender(P>0.05).But the High expression of PRL-3 and VEGF in SNSCC was significantly related with advanced,lower tumor differentiation and lymph node metastasis(P<0.05).3The expression of PRL-3 and VEGF was positively correlated in sinonasal squamous cell carcinomas.Conclusion:The expression of PRL-3 and VEGF in SNSCC may involve in the regulation of tumor growth and differentiation.The expressing intensity may reflect the proliferation activity of sinonasal squamous cell carcinoma cell.PRL 3 and VEGF may promote the tumor metastasis in a synergistic manner. PMID- 29798030 TI - [The relationship between the key nasal symptoms and the level of histamineand leukotriene D4 in serum and nasal secretions in allergic rhinitis]. AB - Objective:To investigate the relationship between main nasal symptoms and the levels of histamine and leukotriene D4(LTD4) in serum and nasal secretions in allergic rhinitis(AR),and provide a preliminary guidance for individualized treatment in AR.Method:One hundred and eight cases of AR were divided into two groups,i.e.sneezing group and nasal congestion group,according to 2014 clinical guidelines for allergic rhinitis from January 2014 to June 2015.The levels of histamine and LTD4 in serum and nasal secretions were determined by enzyme-linked immunosorbent assay(ELISA) and the relationship was explored between the clinical main nasal symptoms score and the levels of histamine and LTD4.Result:The scores of sneezing(5.58+/-2.59)for AR were obviously related to the levels of histamine in serum(8.39+/-4.07)ng/ml and nasal secretion(5.06+/-2.47)ng/ml,(r=0.79,0.78,all P<0.05).The scores of nasal congestion(5.34+/-2.36) for AR were also related to the levels of LTD4 in serum(0.356+/-0.155 ng/ml) and nasal secretion(0.215+/ 0.092)ng/ml,(r=0.74,0.72,all P<0.05).And the levels of histamine(8.39+/ 4.07)ng/ml and LTD4(0.356+/-0.155) ng/ml in serum for AR patients were positively correlated with the levels in nasal secretions(r=0.99,P<0.01;r=0.98,P<0.01).Conclusion:In AR patients,the high levels of histamine and LTD4 in serum and nasal secretions are closely related to the sneezing symptoms and nasal obstruction symptoms,respectively. PMID- 29798031 TI - [Impact of virus infection and related immunity factorson nasal inverted papilloma]. AB - Objective:To explore the relationship between human papilloma virus infection,TGF beta,IL-10,IFN-gammaand nasal inverted papilloma.To explore the relat-ionship between human papilloma virus infection,TGF-beta,IL-10,IFN-gammaand nasal squamous cell carcinoma.Method:Thirty cases of NIP(including 7 cases of recurrent NIP),23 cases of NSCC,19 cases of NP were collected.In situ hybridization(ISH) was used to detect the infection of HPV6/11,HPV16/18.Immunohistochemical technique(EnVision) was used to detect the expression of TGF-beta,IL-10,IFN gamma.Result:The HPV infection rates of 30 cases of NIP,23 cases of NSCC were 43.33%,52.17%.None of the NP cases was infected with HPV.Nine out of 23 cases of primary NIP were positive in HPV infection (39.13%).Three out of 7 cases of recurrent NIP were positive in HPV infection (42.86%).There were significant differences in the HPV infection rate between NIP and NP as well as between NSCC and NP(P<0.05).No significant difference of HPV infection rate was observed between NIP and NSCC or between recurrent NIP and primary NIP(P>0.05).TGF-beta,IL 10,IFN-gammawere expressed in NSCC,NIP and NP.The expression of TGF-betawas significantly different among NIP,NSCC and NP(P<0.01).The expression of TGF betain NIP group was higher than that in NP and NSCC group.There was no significant difference of TGF-betaexpression between NSCC and NP group .The expression of IL-10 was significantly different among NIP,NSCC and NP(P<0.01).The expression of IL-10 in NIP group was lower than that in NP group.There was no significant difference in IL-10 expression between NIP and NSCC or between NSCC and NP.No significant differences of IFN-gammaexpression was observed among NIP,NSCC and NP(P>0.05).There was no correlation between the expression of TGF beta,IL-10,IFN-gammaand HPV infection in NIP and NSCC(P>0.05).Conclusion:HPV infection is related to the pathogenesis of some NIP and NSCC cases.The relationship of between HPV infection and malignance of NIP is not clear.HPV infection is not related to the recurrence of NIP.Abnormal expression TGF-betaand IL-10 may be involved in the pathogenesis of NIP.There is no relationship between IFN-gammaand the pathogenesis and development of NIP.HPV infection is not related with the expression of TGF-beta,IL-10,IFN-gammain NIP and NSCC. PMID- 29798033 TI - [Ultrahigh-frequency hearing thresholds in middleaged and elderly healthy adults]. AB - Objective:To investigate the ultrahigh-frequency(UHF) hearing thresholds in middle-aged and elderly healthy subjects .Method: Healthy subjects(age range: 50 69 ) were divided into two groups,i.e.50-59 year-old group and >59-69 year-old group.Each subject was tested with both conventional frequency(0.25,0.50,1.00,2.00,4.00,6.00 and 8.00 kHz) and ultrahigh frequency(9.0,10.0,11.5,12.5,14.0,16.0,18.0,and 20.0 kHz) audiometry.UHF was performed twice to evaluate the reliability.The best hearings among 20-29 aged healthy adults were considered as normal controls.Results:Seventy five middle aged and elderly subjects were included,with 39 subjects(78 ears) being 50-59 years old and 36(72 ears) being >59-69 year-old.Eighteen subjects(36 ears) aging from 20 to 29 were considers as controls.For the conventional-frequency,the hearing thresholds in middle-aged and elderly people were significantly higher than those in young people(all P<0.05),especially at >=4 kHz.Although the conventional-frequency thresholds in >59-69 year-old group were higher than those in 50-59 year-old,the difference was significant just at 4 kHz(P<0.05).The UHF thresholds in middle-aged and elderly people were significantly higher than those in young people(all P<0.05).The thresholds at 9,10,11.5 and 12.5 kHz in >59-69 year-old people were significantly increased than those in 50-59 year-old counterparts(all P<0.05).Hearing threshold at >=12.5 kHz couldn't be detected in some subjects in middle-aged and elderly group.The response rate at UHF in >59-69 year-old people were just higher than that in 50-59 year-old counterparts (P>0.05),and none responded at 18 and 20 kHz.The standard deviations(SDs) for <14 kHz in 50-59 year-old and for <11.5 kHz in >59-69 year-old subjects,were both higher than that in 20-29 year old counterparts.Above 6 kHz,the SDs in 50-59 year old subjects were significantly higher than those in >59-69 year-old subjects(all P<0.05).Conclusion:For middle-aged and elderly people,the hearing loss may occur from 4 kHz.Hearing thresholds at UHF were increased with age,and it might be used as an early indicator for age-induced hearing loss.However,the UHF sensitivity decreased as the frequency increased beyond 14 kHz. PMID- 29798032 TI - [Effects of inhibiting the phosphorylation of JNK by absorbed INF-gammaon the remodeling of nasal mucosa in allergic rhinitis rats]. AB - Objective:To study the role of phosphorylated JNK(c-Jun N-terminal kinase) on nasal mucosa remodeling in allergic rhinitis(AR) rats and the influence of IFN gammaon IL-1beta,JNK and nasal mucosa remodeling.Method:According to random number table,48 Wistar rats were divided into control group(A group),AR group(B group),IFN-gammagroup(C group) and triamcinolone acetonide group(D group).The rats in group B,C and D were sensitized and provocated for inducing AR by intraperitoneal injection of ovalbumin(OVA) and Al(OH)3.Thirty minutes before intranasally challenged,rats in three groups were administrated by instillation of PBS,IFN-gammaand triamcinolone acetonide into nasal cavities,while the group A rats were administrated by saline solution.Ten rats in each group were selected to enter the final experiment.The density of IL-1betain serum and nasal lavage fluid were tested by ELISA.The mean absorbance (mA) of phosphorylated JNK and c Jun were tested by immunohistochemistry.Western Blot detected the P-JNK level in nasal tissue homogenate.Result:The density of IL-1betain serum and nasal lavage fluid in group C and group D were significantly lower than that of group B (P<0.01).Immunohistochemistry study showed that the protein expression level of phosphorylated JNK and c-Jun of nasal mucosa were significantly increased in group B,but significantly reduced in group C and group D .The mA of phosphorylated JNK and c-Jun in group B were significantly higher than those in the group C and group D(P<0.01).The Western blot showed that the P-JNK of nasal tissue homogenate in group B was higher than that of group C and group D (P<0.01).Conclusion: The phosphorylation of JNK played an important role in nasal mucosa remodeling.IFN-gammacould inhibit the phosphorylation of JNK and reduce the nasal mucosa remodeling.The mechanisms may be achieved through down regulation of IL-1beta. PMID- 29798034 TI - [A study on the X-ray measurement predictors of difficult laryngealexposure in patients undergoing microlaryngosurgery]. AB - Objective:This paper seeks to identify useful and reliable indicators for predicting the occurrence of difficult laryngeal exposure(DLE) in microlaryngosurgery.Method:Sixty-two patients were given physical examinations,including 4 general parameters:age,sex,BMI,and MMI,and 14 physical measurement parameters(TA,UIA,LIA,IG,LIMD,MA,MCD,MH,MDI,HMD,TMD,SMD,TMA,THUIA).Univariate analysis,stepwise regression analysis and ROC curve analysis were employed to identify parameters with the potential to predict DLE.Result:We found sex(P<0.05) showed significant correlation with the laryngeal exposure score(P<0.05).We also found LIMD,MA,TMA and THUIA to be reliable DLE predictors.The cutoff values for predicting DLE were LIMD>4.53cm,MA>115.5 degrees ,TMA>99.2 degrees ,and THUIA>152.6 degrees .Conclusion:X-ray measurement predictors of LIMD,MA,TMA,and THUIA before operation are important for the prediction of DLE.Sex is also the reliable DLE predictor.Males were prone to DLE. PMID- 29798035 TI - [The significance and application of serum eosinophil cationic proteinand IgG4 antibody in patients with allergic rhinitistreated by allergic specific immunotherapy]. AB - Objective:To study the significance and application of serum eosinophil cationic protein(ECP) and IgG4 antibody in patients with allergic rhinitis treated by allergic specific immunotherapy.Method:The level of IgG4 antibody and eosinophil cationic protein in serum was measured in 33 cases of allergic rhinitis before treatment and half a year and one year after treatment.The change of ECP level was observed in different age groups,and the relationship between serum IgG4 and ECP after treatment was analyzed.Result:IgG4 antibody in the serum significantly increased after treatment,and the difference was statistically significant(P<0.05).In the serum ECP content gradually reduced after treatment,and the difference was statistically significant(P<0.05).No obvious difference in ECP level was observed among dfferent age groups after treatment (P<0.05).The level of serum IgG4 was negatively correlated with serum ECP level despite statistical insignificance(r=-0.138,P>0.05).Conclusion:ECP is a sign of eosinophil activation,which is an important factor leading to the nasal inflammation.The content of serum ECP can be used as an indicator for patients with allergic rhinitis recieving nonspecific immune treatment .IgG4 antibody is a relatively reliable indicator to evaluate the treatment effect of specific immunotherapy,and may be negatively related to the serum ECP levels. PMID- 29798037 TI - [Expression of Foxm1 in chronic sinusitis and itsrelationship with MUC5AC]. AB - Objective:To explore the expression of Forkhead box protein m1(Foxml) in the sinus mucosa of patients with chronic rhinosinusitis(CRS) and the relationship between Foxm1 and MUC5AC for further understanding of the pathogenesis of CRS.Method:We obtained the sinus mucosa from 25 CRS with polyps(CRSwNP) patients and 25 CRS without polyps (CRSsNP) patients as two experimental groups.Nasal mucosa from 15 normol cases were obtained as control group.We used HE,Periodic acid-schiff staining to observe the histopathological change of each sample.The expression of Foxm1 and MUC5AC were determined by immunohistochemistry(IHC) and qRT-PCR in each group.We also analysed the relationship between Foxm1 and MUC5AC.Result:The HE and PAS staining showed that in the CRSwNP and CRSsNP patients,the main histopathological features was the hyperplasia of goblet cell,inflammatory cell and submucosal gland.IHC showed that Foxm1 and MUC5AC expression were higher in CRSwNP and CRSsNP compared with normal sinus mucosa.qRT PCR also revealed that Foxm1 and MUC5AC expression was higher in CRSwNP and CRSsNP than in normal mucosa(P<0.05).Foxm1 and MUC5AC had a significant positive correlation.Conclusion:The expressions of Foxm1 and MUC5AC were increased in CRS,and Foxm1 may play an important role in the process of hypersecretion of MUC5AC in CRS. PMID- 29798036 TI - [The effect of combined therapy on seasonal allergic rhinitis]. AB - Objective:To observe the effect of combined therapy on seasonal allergic rhinitis(AR) and quality of life.Method:Ninety-six patients with severe seasonal AR unresponsive to intranasal corticosteroids alone were divided randomly into nasal budesonide group(group A),Nasal Budesonide combined with fexofenadine hydrochloride group(group B),and budesonide combined with montelukast group(group C).The symptom scores,Uni-VAS,and rhinoconjunctivitis quality of life(RQLQ) were evaluated 2 and 4 weeks after treatment initiation.Result:In the group B and C,the symptom scores,Uni-VAS,and RQLQ were significantly lower than the group A(P<0.05).As for nasal itching(after 2 weeks),rhinorrhea and sneezing,the symptom scores and Uni-VAS of group B were significantly lower than that of group C(P<0.05).However,compared to group B,the improvement of nasal obstruction in group C was much better(P<0.05).There was no significant difference in other symptoms and RQLQ.Conclusion:For patientswith severe seasonal AR unresponsive to intranasal corticosteroids alone,combined therapy can help alleviate clinical symptoms and improve quality of life.The combination of drugs should be individulized based on the severity of symptoms. PMID- 29798038 TI - [Preliminary analysis of influencing factors on source of snoring sound]. AB - Objective:To investigate the main factors affecting the source of snoring sound of snoring patients.Method:Seventy-three patients with either simple snoring or obstructive sleep apnea-hypopnea syndrom(AHI<=40) underwent routine ENT examination,CT scanning(in awake condition) and drug-induced sleep endoscopy.The sources of snoring sound were observed.The neck circumference,body mass index and CT data were measured.Result:The sources of snoring sound of the 73 cases were divided into three types in general: palatal fluttering based group(Group I),lateral wall vibration based group(Group II) and palatal fluttering together with vibration of lateral wall based group(Group III).The minimum lateral caliber of retropalatal region and retroglossal region,the ratio of minimum anteroposterior/ lateral caliber of the two regions,the thickness of pharyngeal lateral wall had statistical differences.The main influencing factors on the source of snoring sound between Group II and Group I were the ratio of minimum anteroposterior/lateral caliber of retropalatal region and the mean thickness of pharyngeal lateral wall.The influencing factor between Group III and Group I was the mean thickness of pharyngeal lateral wall.Conclusion:The ratio of minimum anteroposterior/lateral caliber of retropalatal region and the mean thickness of pharyngeal lateral wall are the main factors affecting the source of snoring sound of snoring patients. PMID- 29798039 TI - [Horizontal semicircular canalvideo head impulse test in normaladults:normal value and age distribution]. AB - Objective:To study the parameters of video head impulse test (vHIT) for horizontal semicircular canal and explore its application when evaluating angular vestibular-ocular reflex (VOR) in adults.Method:vHIT were applied to 80 adults without prior vertigo or dizziness history.Parameters provided by the software included instantaneous gain(40 ms,60 ms,80 ms),regression gain,asymmetry value,corrective saccades(latency,peak velocity,occurrence rate).Result:The mean horizontal VOR velocity gain of normal subjects was 0.877+/-0.171,0.944+/ 0.133,0.967+/-0.130 at 40 ms,60 ms,80 ms respectively.Regression gain of horizontal VOR is 0.944+/-0.090.The lower limit of normal horizontal VOR velocity gain was 0.73 at 60 ms and 0.80 as regression gain.All velocity gains declined by age,although there were no statistically significant difference(P>0.05).Asymmetry value was 5.60+/-3.46.Corrective saccades occurred in 28+/-15 of normal subjects,while latency and peak velocity was (200.87+/-0.34)ms and (97.7+/-40.1) degrees /s.Conclusion:The study found that horizontal VOR instantaneous gain value and regression gain value decreases slightly with age,which should be considered in clinical application. PMID- 29798040 TI - [Analysis of acute sinusitis or nasal furuncle derived orbitalcellulitis in children: review of 18 cases]. AB - Objective:To analyze the diagnosis and treatment of acute sinusitis or nasal furuncle derived periorbital cellulitis in children.Method:The clinical data of 18 children with acute sinusitis or nasal furuncle derived orbital cellulitis was analyzed retrospectively.Result:Sixteen cases(88.89%) had acute sinusitis and 2(11.11%) had furuncle of nose.All cases were treated with antibiotics and steroids.And 16 cases were cured and the other two received surgery.The median length of hospitalization was 7.33 days(5-13 days).Conclusion:Sufficient antibiotics combined with steroids and local treatment is critical in treating pediatric orbital cellulitis.Timely and decisive surgical intervention can effectively control the progression of disease. PMID- 29798041 TI - [Modified radical mastoidectomy on"drum sinus" type chronic suppurative otitis media:our experience]. AB - Objective:To our experience of modified radical mastoidectomy on "drum sinus" type chronic suppurative otitis media.Method:We measured the size of tympanic sinus,the extent of meningeal plate lowering and the extent of sigmoid ante displacement in 54 patients of chronic suppurative otitis media,and determined the criterion of "drum sinus".The patients who comply with the criterion received modified radical mastoidectomy and tympanoplasty via epitympanum approach.The patients were followed up for at least 3 months,The time of dry ear,growth of repaired tympanic membrane,and any complications such as dizziness,facial paralysis,cerebrospinal fluid leakage were recorded.Result:Twenty-nine out of the 54 CSOM patients complied with the criterion of drum sinus.Two cases were lost to follow-up.Therefore,27 cases were included in the study.Three months after the operation,the rate of dry ear was 81.5% Tympanic membrane was successfully repaired in 77.8% of the patients.Three cases had dizziness after operation.No facial paralysis or cerebrospinal fluid leakage was observed.Conclusion:For"drum sinus" type chronic suppurative otitis media,the modified radical mastoidectomy and tympanoplasty via epitympanum approach can be taken. PMID- 29798043 TI - [Sorbalgon strips used in elderly intractable epistaxis]. PMID- 29798042 TI - [Effect observation of cryotherapy in the treatment of nasal cavity adhesion]. AB - Objective:To investigate the effect of cryotherapy in the treatment of nasal cavity adhesion.Method:Patients with nasal cavity adhesion(68 sides in total)were randomly devided into the experimental group(34 sides) and the control group(34 sides).The experimental group were treated with cryotherapy and the control group with traditional separation surgery.The subjective symptoms and recovery of nasal mucosa were observed at 1,3 and 8 weeks after treatment.Result:1The postoperative nasal obstruction symptom evaluation score in the experiment group were significantly better than in the control group(P<0.05).2The VAS score of discomfort during therapeutic process in the experiment group were significantly better than in the control group(P<0.05).3The endoscopic mucosa morphology score at 1,3 and 8 weeks postoperatively in the experiment group was significantly better than that in the control group(P<0.05).4The cure rate of experiment group was 97.1% and 76.5% of control group .The cure rate of experiment group was significantly higher than that of the control group(P<0.05).Conclusion:Cryotherapy is a simple and safe therapeutic method in the treatment of nasal cavity adhesion with less discomfort,higher therapeutic effect and better mucosa recovery.Cryotherapy is more likely to be accepted by patients. PMID- 29798044 TI - [Research of nasopharyngeal carcinoma and the applicationof epstein-barr virus immediate early protein]. AB - Epstein-barr virus is closely related to the occurrence and development of nasopharyngeal carcinoma;EB virus immediate early protein Zta and Rta is the control factor for the virus to enter the replication and cleavage stage.At present,ELISA method is commonly used to detect serum Zta and Rta related antibodies in the clinical as one of the serological indicators for early nasopharyngeal cancer screening and the auxiliary diagnosis. PMID- 29798045 TI - [Current status of diagnosis and treatment of Thornwaldt cyst]. AB - Of Thornwaldt cyst is a congenital disease,nasopharyngeal top and posterior wall of the center of the infected cyst,which is rare in clinic,a lower incidence is a benign lesion,most cases have no symptoms,mostly through electronic endoscopic imaging system or radiological examination have been sent.Domestic reports about Thornwaldt cysts are also less,so this paper refer to the domestic and foreign literatures about the Thornwaldt cyst in recent years,the diagnosis and treatment of this disease is reviewed. PMID- 29798046 TI - [Drug treatment of allergic rhinitis based on immunological mechanisms of progress]. AB - The current treatment of allergic rhinitis remains a challeng for clinician while developing non-specific immunotherapy can make up the disadvantages of routine medications.It has solved the problems like long treatment course of specific immunotherapy or adverse reactions;It has improved the theoretical basis and treatment methods of airway allergic disease.This article reviwed the recent clinical studies about mechanisms of allergic rhinitis. PMID- 29798047 TI - [Research progress of animal model of allergic rhinitis]. AB - The animal model of allergic rhinitis is ciritical for the study of this disease.Guinea pig,mouse,rat,rabbit and other animals can be selected.Allergen includes ovalbumin,pollen,dust mites,available fungi,roundworm and schistosome antigen.Aluminum hydroxide adjuvant is most commonly used.To enhance the sensitivity,nasal drops can be selected,inhalation and multi-point subcutaneous injection is optional.Nasal itching,sneezing,clear nasal discharge ,or specific histopathological and immunological results can indicate the success of modeling.Immunological test is the most important standard to determine whether the model is successful or not.This review summarizes the recent advances in the study of animal models of allergic rhinitis. PMID- 29798048 TI - [Desmocollin-1 significant correlated with the tumorigenesis and prognosis of HNSCC]. AB - Objective:To explore the correlation between the expression of desmocollin?1and the tumorigenesis and prognosis of HNSCC.Method:Five datasets of HNSCC from the GEO were analyzed. A tumor tissue microassay was chosen for further test. The expression of DSC1 of TMA was detected by immunohistochemical staining. Result:The expression of DSC1 was significantly increased in HNSCC. Meanwhile, the expression of DSC1 was much higher in poor-differentiated tumor than the well?differentiated tumor in HNSCC. What's more, the HNSCC patients with lower expression of DSC1 had better outcomes. Conclusion:The results were according with the results of statistical analysis with the bioinformatics data from GEO, indicating that DSC1 significant correlated with the tumorigenesis and prognosis of HNSCC. PMID- 29798049 TI - [Value of videonystagmography and electrocochleography in prognosis prediction of patients with acute low-tone sensorineural hearing loss]. AB - Objective:To predict the prognosis of acute low?tone sensorineural hearing loss(ALHL)by using the videonystagmography(VNG) and electrocochleography(ECochG).Method:A retrospective study was done in 70 patients with ALHL after long-term follow-up. The recurrence rate and rate of progression to definite Meniere 's disease were determined according to the results of VNG and ECochG tests at the onset of the first episode of hearing loss.Result:Twenty?nine patients(41.4%)experienced recurrent hearing loss and 5 patients(7.1%)developed to Meniere's disease. In patients with an elevated SP/AP ratio and spontaneous nystagmus, the recurrence rate was 81.8%. However, in those with a normal SP/AP ratio and without spontaneous nystagmus, the recurrence rate was 23.3%.There was a statistically significant difference in the progression rate of Meniere's disease between the groups with(15.2%) and without spontaneous nystagmus.Conclusion:It has a certain reference value to predict prognosiswhen spontaneous nystagmus and an elevated SP/AP ratio are detected on initial examination in patients with ALHL. PMID- 29798050 TI - [Expression and significance of PDK1 and NF-kappaB in the middle ear cholesteatoma]. AB - Objective:To detect the expression of 3-phosphoinositide-dependent kinase-1(PDK1) and nuclear factor-kappaB(NF-kappaB) in human middle ear cholesteatoma tissue and to analyze their correlation.Method:Immunohistochemical method was taken to detect the expression and location of PDK1 and NF-kappaB in 60 cases of cholesteatoma tissue and 30 cases of normal ear skin specimens.SPSS 19.0 software was used to analyze the data. Result:Immunohistochemistry revealed PDK1 was positive in cytoplasm and the positive expression rate in cholesteatoma was significantly higher than normal skin (P <0.05); NF-kappaB expressed in the nucleus of cholesteatoma and the positive expression rate in cholesteatoma significantly higher than normal skin(P <0.05);In cholesteatoma specimens,there was a significant positive correlation between protein PDK1 and NF-kappaB(P <0.05). Conclusion:Abnormal expression of PDK1 and NF-kappaB may be related to the proliferation of cholesteatoma epithelium and they reinforce each other. PMID- 29798051 TI - [Expression of Has-miR-93-5p in laryngeal squamous cell carcinoma and its clinical significance]. AB - Objective:To investigate the expression of has-miR-93-5p on human laryngeal squamous cell carcinoma and the influence on malignant phenotype of Hep-2 cell.Method:The expression of has-miR-93-5p of paraffin samples in LSCC was determined by looped-primer Real-time PCR, and the relationship between the expression and the clinical pathological parameters was analysed. The has-miR-93 5p Inhibitor sequence was transfected into Hep-2 cells as the Inhibitor group. Using the MTS assay, Edu and colony formation assay to investigate the change of cell viability,proliferation and clone formation ability after transfection. Transwell invasion assay was used to detect the changes of cell migration and invasion ability. Flow cytometry was used to detect the changes of cell cycle and apoptosis.Result:The relative expression of has-miR-93-5p in LSCC was 11.148+/ 1.141,which was higher than in normal tissues of adjacent to carcinoma1(985+/ 4.547)(P <0.01).The constituent ratio of has-miR-93-5p high expression in the group of low differentiation, T3+T4 and lymphatic metastasis was 69.8%,76.5%and 89.5%,which was higher than the group of high differentiation,T1+T2 and non?lymphatic metastasis respectively(P <0.05), Inhibition the expression of has miR-93-5p in vitro in Hep-2 cells could obviously inhibit the cell vitality, proliferation, clone, migration, and invasion ability, also could retardant the cells in G2/M phase, and promote its apoptosis.Conclusion: has-miR-93-5p might be an important molecule in pathogenesis of laryngeal squamous cell carcinoma. It could inhibit malignant phenotype of laryngeal squamous cancer cells when has-miR 93-5p expressionwas suppressed in vitro. PMID- 29798052 TI - [The role of acoustic analysis of fundamental frequency in differentiating arytenoid dislocation from vocal fold paralysis]. AB - Objective:Analysis of the sustained vowels of acoustic parameters in arytenoid dislocation and vocal fold paralysis. To investigate their acoustic characteristics and evaluate the role of this acoustic analysis method in differentiating arytenoid dislocation from vocal fold paralysis. Method:Thirty three cases with unilateral vocal cord movement disorders were collected.All cases were divided into arytenoid dislocation group and vocal fold paralysis group through the laryngeal electromyography. Each group was further devided into male group and female group. The voice signals of sustained vowel of /a/ were measured using the software MDVP and obtain the acoustic parameters(Jitter, Shimmer, SPI and Fo). The acoustic characteristics between the two groups were observed and compared. Results were analyzed using Rank sum test for group design.Result:There were significant differences in Fo between arytenoid dislocation group and vocal fold paralysis group in both male and female group(P <0.05). And mean rank order of Fo in arytenoid dislocation group was greater than vocal fold paralysis group. There were no significant differences in jitter,shimmer and SPI between arytenoid dislocation group and vocal fold paralysis group(P >0.05).Conclusion:Mean rank order of Fo in arytenoid dislocation group is greater than vocal fold paralysis group in both the male and the female group. Fo is of value in differentiating arytenoid dislocation from vocal fold paralysis. This provides a theoretical basis for the acoustic analysis method to identify these two diseases. PMID- 29798053 TI - [Significance of five symptoms scoring sheet in the clinical diagnosis of BPPV]. AB - Objective:To identify the validity of five symptoms scoring sheet that based on the patients who are suffering from benign paroxysmal positional vertigo(BPPV), and explore its effects and significance in the clinical diagnosis of BPPV.Method:A total of 484 patients with vertigo were included. All the patients were firstly assessed with five symptoms scoring sheet(repeated transient vertigo or aggravating vertigo during looking up, bending, getting out of bed, rolling over in bed and quick head movements) before being confirmed by Dix-Hallpike test and rolling test. Evaluating the predictive ability of this scoring sheet in the diagnosis of BPPV with ROC analysis.Result:According to the ROC analysis , the sensitivity and specificity were 95.4% and 80.3% respectively when the score >7, and an area under receiver operating characteristic curve(AUC) was 0.923.Conclusion:Five symptoms scoring sheet is useful and convenient in diagnosing BPPV, which can be used in BPPV screening and guide the vertigo patients to receive further test and treatment. PMID- 29798054 TI - [The evaluation of hearing aid effect in presbycusis]. AB - Objective:To evaluate the effect of hearing aid in presbycusis. Method:Using the method of international outcome inventory for hearing aids(IOI-HA)and medium acoustic intensity(65 dBSPL) word recognition score(WRS), to evaluate the effect of hearing aid in moderate and severe presbycusis. Result:After the hearing aid of moderate presbycusis, The improved value of monosyllabic words and recognition rate in quite and noise statement(SNR=5) were 31.15%, 23.21%, 44.11%.However, improved values in severe presbycusis were 37.51%, 48.47%,50.17%, before and after hearing aid, the difference of the improved average value was statistically significant(P <0.05); Both the moderate and severe presbycusis were satisfacted with hearing aid.The IO-HA scores of moderate and severe presbycusis ranged from 15 to 34.The difference of IOI?HA score of moderate and severe presbycusis had no statistical significance(P >0.05); moderate and severe presbycusis with high satisfaction with HA of quiet statement,and low satisfaction of monosyllabic words listening, and the degree of satisfaction was higher in patients with moderate to severe hearing loss in noise statement.Conclusion:Speech audiometry is an important method to assess the effect of hearing aid; IOI-HA is a time?consuming short, subjective method.The combine of multiple evaluations have guiding significance to debugging of hearing aid expected effect and hearing aid device. PMID- 29798055 TI - [Evaluation of the frontal recess cells with image-guided system]. AB - Objective:To investigate the value of image-guided system in identifying the frontal recess cells.Method:We collected 30 cases that underwent image-guided frontal sinus surgery from November 2014 to December 2015. These frontal recess cells were devided into 2 groups based upon their locations in the frontal sinus ostium. Group A consists of the agger nasi cells, type Ifrontal cells, type II frontal cells and suprabullar cells; group B consist of type III frontal cells, type IV frontal cells, frontal bullar cells, interfrontal sinus septal cells and supraorbital ethmoid cells. Visual analogue scale (VAS) was used to evaluate the degree of demand of image guide system on the location of frontal recess cells, and then analyzed the value of image guided system on the frontal recess cells.Result:In all 30 patients the image?guided frontal sinus surgery was successfully completed.The demand degree of image-guided system on frontal recess cells by VAS was slight for the agger nasi cells, type Ifrontal cells, type II frontal cells and suprabullar cells; the demand degree was general for the frontal bullar cells and interfrontal sinus septal cells; the demand degree was obvious for type III frontal cells, type IV frontal cells and supraorbital ethmoid cells. Frontal recess cells of group B were more depended on image guided system than those of group A, and the difference was signicant(P <0.01).Conclusion:Image?guided system is valuable in distinguishing for type III frontal cells,type IV frontal cells supraorbital ethmoid cells and interfrontal sinus septal cells.Furthermore,it is significantly helpful for accurate removal of these frontal recess cells in endoscopic frontal sinus surgery. PMID- 29798056 TI - [The application of extended high frequency audiometry in detecting the early hearing loss for thalassemia]. AB - Objective:To preliminarily explore the clinical significance of extended high frequency audiometry in evaluating the early hearing loss for thalassemia.Method:Pure tone audiometry(PTA) included conventional pure tone audiometry and extended high frequency audiometry were obtained on the pre and post-treatment day in 60(117 ears) patients from September in 2013 to October in 2014. Result:The averages of conventional pure tone audiometry for 117 cases were(15.72+/-11.62)dBHL on the pre-treatment day and(15.40+/-12.24)dBHL on the post-treatment day. There were no significant differences in PTA(P >0.05). But the hearing without detection rate was higher than before especially at 18 and 19 kHz. The differences of the hearing without detection rate between the pre treatment and the post-treatment day were statistically significant(P <0.05?).Conclusion:The extended high frequency may be more sensitive in evaluating the early hearing loss for thalassemia. PMID- 29798058 TI - [The clinical analysis of infection of the deep neck space with superior mediastinal abscess]. AB - Objective:To study the etiology, presentation, diagnosis and treatment of infection of deep neck space with superior mediastinal infection in order to accumulate experience in clinical diagnosis and treatment.Method:We reviewed medical records of 15 patients who were diagnosed with deep neck infection with superior mediastinal infection and those who were hospitalized in Guizhou provincial people's hospital from Janurary 2011 to July 2015.The patients were screened retrospectively for demographic characteristics, presenting symptoms, laboratory examinations, imaging features, bacteriologies and etiologies. The treatment and outcomes of the patients were investigated.Result:In 15 patients, 7 cases(46.67%) were related to foreign body in esophagus, 3(20%) cases were related to peritonsillar abscess, 2(13.33%) cases who had diabetes with poor blood glucose control were related to exodontias, 3(20%) cases were related to unknown reasons. The serum CRP[(151.82+/-22.12)mg/L] at the time of admission had a positive correlation with the time of hospitalization. The time of CRP decreased to normal range after admission [(15.3+/-2.1)d] were apparently related to the hospitalization time[(23.8+/-4.1)d]?(r=0.79, P<0.01). The results of bacteria culture of 7 cases was positive(46.67%), 2 cases were infected by Klebsiella pneumoniae and 1 case was mixed with Escherichia coli, 2 cases were infected by the Streptococcus viridans infection, 2 cases were infected by Hemolytic streptococcus A group and B group, 1 case was infected by Staphylococcus Aureus. Appropriate antibiotics for organisms were given based on the results of culture identification and empiric therapy. The patients with abscesses were treated with cervical and superior mediastinal drainage. In 15 patients who were complex treatment, 4 patients including 2 patients with diabetes were succumbed to the disease (mortality is 26.67%),11 patients were healed up(effective rate is 73.33%).Conclusion:The patients with deep neck space infection with superior mediastinal infection had rapid onset, rapid development and the patients with diabetes had high mortality. The patients should be analyzed in detail the history and clinical manifestations combined with imaging examination, bacterial culture and drug sensitive test and so on in order to determine the diagnosis. The patients should be cured with effective antibiotics and active surgical intervention. PMID- 29798057 TI - [The application of autologous cartilago auriculae in posterior wall of external auditory canal reconstruction and tympanoplasty]. AB - Objective:To evaluate the value of of autologous cartilago auriculae in posterior wall of external auditory canal reconstruction and tympanoplasty after modified radical mastoidectomy.Method:To determine the outcome of surgery for chronic suppurative otitis media with choleteatoma. The open mastoidectomy and tympanoplasty were performed on sixty patients aged 20-62 years old, and the average age was(43.16+/-9.43)years old, which includes 31 males and 27 females at our department in the period from September 2011 to September 2014. 58 patients all underwent modified radical mastoidectomy.Study group chose collected intraoperative cortical mastoid bone as a filler combined with autologous cartilago auriculae and temporal fascia muscle-periosteal flap covering the cavity and tympanoplasty.Control group chose collected intraoperative cortical mastoid bone as a filler temporal fascia muscle-periosteal flap covering the cavity. The hearing improvement at the time of achieving dry ear,3 months and 6 months after surgery were evaluated for both groups.Result:There are significant differeence between two groups in improvement of hearing and dry ear time,according to follow-up and analysis of therapeutic efficacy(P <0.05), There was no recurrence of cholesteatoma in 2 groups.Conclusion:The application of autologous cartilago auriculae in posterior wall of external auditory canal reconstruction and tympanoplastycan that can get more in line with the external auditory canal and the volume of physiological structure state of near normal tympanic cavity, dry ear and hearing improvement was satisfied.The autologous cartilago curiculae is suitable for repairing materials of open radical operation. PMID- 29798059 TI - [Flunarizine in the prophylaxis of vestibular migraine:a randomized controlled trial]. AB - Objective:To evaluate the efficacy and safety of flunarizine in patients with vestibular migraine(VM)as a prophylactic medication. Method:This randomized control trial was undertaken in patients with definite VM. Behavior changes were advocated to all the patients to avoide certain foods and beverages, as well as changes in lifestyle and habits.Patients in arm A received 10-mg flunarizine daily for 3 months along with betahistine 12 mg Tid for 48 h during episodes, and arm B received only betahistine for 48 h during episodes. Frequency. duration and intensity of vertiginous episodes and the main side?effects were noted at the start of the study and at the end of 3 months.Result:A total of 23 patients who were diagnosed with definitive migrainous vertigo completed the study. The frequency,duration and intensity of vertiginous episodes showed a significan improvement in both group(P <0.05).Analysis of the frequency, duration and intensity between arm A and arm B showed that frequency improved to a significant degree(P <0.05),but the duration and intensity of vertigo between the two groups did not improve to a significant degree(P >0.05). Severe adverse events were not found. Conclusion:Flunarizine is safe and effective for the prophylaxis treatment of VM. PMID- 29798060 TI - [Neuromedin U expression related to the occurrence of laryngeal carcinoma and the regional lymph node metastasis]. AB - Objective:Research Institute of Otolaryngology?Head and Neck Surgery, Renmin Hospital of Wuhan University Neuromedin U(NMU) plays important role in immune regulation in a variety of tissues and organs, and this study intends to explore the correlation between the local metastasis of laryngeal cancer and the expression of NMU.Method:A retrospective analysis was made on 240 cases of laryngeal carcinoma in our hospital. The expression of NMU was detected by immunohistochemistry. Microassay tissue(TMA) was used to further analyze the correlation of NMU protein expression with T, N and M stage in laryngeal carcinoma.Result:Cervical lymph node metastasis was present in 51.4% of 240 laryngeal carcinoma patients. The expression of NMU was significantly higher in the patients with local metastasis than those without metastasis. And along with tumor progression, NMU expression increased significantly.Conclusion:The expression of NMU in laryngeal carcinoma was significantly correlated with the metastasis of laryngeal carcinoma and TNM stage, which indicated that NMU may be involved in the development of laryngeal carcinoma metastasis. PMID- 29798061 TI - [The contrast analysis of endoscopic thyroidectomy by complete areola approach and conventional open thyroidectomy]. AB - Objective:To compare the clinical efficacy between the endoscopic thyroidectomy by complete areola approach and the conventional open thyroidectomy.Method:One hundred and twenty-one cases of endoscopic thyroidectomy by complete areola approach or conventional open thyroidectomy patients were reviewed retrospectively, whose operation time, median blood lose, volume of postoperative drainage, incision scar formation rate and patient satisfaction were observed and compared.Result:There were obvious advantages in the median blood lose, volume of postoperative drainage, incision scar formation rate and patient satisfaction in the group of endoscopic thyroidectomy by complete areola approach comparing conventional open thyroidectomy. The difference was statistically significant(P <0.05).Conclusion:The method of endoscopic thyroidectomy by complete areola approach is obviously better , which has many advantages, such as Less bleeding, less volume of wound drainage and small skin incision scar. The patients were satisfied with the treatment.It is worthy of clinical application. PMID- 29798063 TI - [The application of the self-made cervical incision protection sleeve in thyroid operation]. PMID- 29798064 TI - [The application of homemade negative pressure aspirator in the auricular pseudocyst]. PMID- 29798062 TI - [Preliminary study on the relationship between cervical spondylosis and sudden deafness]. AB - Objective:To explore the prognosis factors and clinical features of 32 patients with sudden deafness, and further invested the relationship between cervical spondylosis and sudden sensorineural hearing loss.Method:Thirty-two cases with sudden deafness of ENT, Neurology,rehabilitation medicine department in Shanxi Provincial people's Hospital from 2014 to 2015 were collected. The clinical data, radiographic data and disease prognosis were analysed. Result:Thirty-two cases in the cervical four bit tablets vertebral artery type positive rate for: 83.87%, neck vascular ultrasound positive rate for: 55.56%, cervical MRI or MRA shows vertebral artery narrow who positive rate for: 77.42%; three items check the appeared of positive number accounted for total cases number of proportion followed by for: cervical four bit tablets for: 65.96%, neck vascular ultrasound for: ?57.45%?, cervical MRI or MRA for: 65.96%; three species check integrated check out rate for: 95.74%.Conclusion:Sudden deafness in patients with cervical spondylosis of vertebral artery type?detection rate is very high, description of vertebral-artery-type cervical spondylosis is likely to be one of the factors influencing the prognosis of sudden hearing loss, sudden hearing loss and there is a certain correlation between cervical spondylosis. PMID- 29798065 TI - [Experimental study on the effect of two kinds of wet chemical solution on the laryngeal carcinoma patients with tracheotomy]. PMID- 29798066 TI - [Clinical analysis of ear,nose and throat neuroendocrine carcinaoma]. PMID- 29798067 TI - [One case of Horner's syndrome after thyroid gland operation]. AB - The patient find the nodule unintentionally for 2 weeks, painless, no voice hoarse, no swallowing and drinking difficulties. no dizziness, no fatigue, no tremor of the hand, no irritability,no palpitations, no fever chills, no nausea, no vomiting, no chest tightness, no shortness of breath and other discomfort.Ultrasonic report:The size of thyroid was normal, and was scattered in the middle of the right lobe with a large solid echo of about 12 mm*7 mm. The left lobe of the thyroid gland was found to have an echo of the size of about 10 mm*7 mm?,the shape was irregular,the boundary was unclear, lymph nodes with no obvious swelling in the neck. CDFI: right lobe of the thyroid low echo mass surrounding the actuate color flow, short rod color flow; left thyroid lobe inferior echo mass around and see the short rod color flow.Diagnose:nodular goiter;subacute thyroiditis;Hornor's symptoms. PMID- 29798068 TI - [The expericence of diagnosis and treatment of foreign body within the pharyngeal soft tissue(3 cases)]. AB - Through the diagnosis and treatment of the foreign body in the soft tissue of phargnx,reduce missed diagnosis. Flexible using of imaging methods for diagnosis and localization,and selecting the best surgical approach are important. PMID- 29798070 TI - [A case of ectopic teeth in ethmoid sinus removed under endoscopic surgery]. AB - In this paper, we report a case of ectopic teeth in the right ethmoid sinus which was successfully removed by nasal endoscopic surgery. PMID- 29798069 TI - [Reported of 2 cases relapsing polychondritis]. AB - Clinical data of two cases of relapsing polychondritis were reported and the relative literatures were reviewed. The two patients diagnosed relapsing polychondritis after clinical and laboratory examinations.The first case was mild , no larynx and trachea involvement, and her condition improved and controlled after glucocorticoid treatment;The second case which involved larynx and trachea caused breathing difficulty. Two years later he died of lung infection and respiratory failure despite a variety of treatment methods. Relapsing polychondritis is very easily misdiagnosed, early diagnosis and treatment can slow the progression of the disease, for patients with violations of the larynx and trachea should pay close attention to disease progression, tracheotomy or place endotracheal memory alloy stent when necessary. PMID- 29798071 TI - [The diagnosis and treatment progress of vocal fold leukoplakia]. AB - Vocal fold leukoplakia is a descriptive diagnosis, and can be divided into simple hyperplasia, precancerous lesions(with atypical hyperplasia) and invasive carcinoma according to pathological types. Because of a close relationship with the laryngeal carcinoma, knowing the risk factors and treatment methods of vocal fold leukoplakia has grate significance in preventing the malignant change and recurrence. This paper summarizes the recent progress in clinical diagnosis and treatment of vocal cord leukoplakia, mainly including risk factors, means of examination, treatment and prognosis. PMID- 29798072 TI - [The effect of OSAHS on middle ear and inner ear vestibule function advances]. AB - Obstructive sleep apnea hypopnea syndrome(OSAHS) as a common frequently?occurring disease, it can cause repeated episodes of hypoxaemia and hypercapnia during sleep. With long period of hypoxaemia, obvious pathological changes and dysfunction emerged in heart,brain and lung then all kinds of clinical symptoms appear. Because of the middle ear and inner ear themselves anatomical characteristics and blood supply of regulating mechanism, they often has been damaged before the other important organ damage. As scholars have in?depth study of the auditory system complications in patients with OSAHS, various influence of OSAHS on the middle ear,inner ear also gradually be known.This paper will review the effect of OSAHS on middle ear, inner ear and vestibule function, hope to have some application value for clinical work. PMID- 29798073 TI - [Expression and significance of serum insulin-like growth factor-1 in patients with obstructive sleep apnea hypopnea syndrome]. AB - Objective:To investigate the expression and significance of serum insulin?like growth factor-1(IGF-1) in adult patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Method:One hundred and seven patients of OSAHS diagnosed with PSG were included in the observation group,which were divided into heavy, medium and light group according to AHI.Fifty case of healthy people without OSAHS were included in control group.Serum IGF-1 were measured by ELISA. Thirty patients of heavy OSAHS received surgery and CPAP treatment for three months,and were retested the levels of IGF-1 and PSG six months later.Result:1With the increase of OSAHS severity, the levels of serum IGF-1 were gradually decreased (F=37.732,P<0.01). There was no significant difference between mild group and healthy people (P>0.05), while there was significant differences between the remaining groups (P<0.01). 2Serum IGF-1 level has no correlation with BMI and age in OSAHS patients(P>0.05), and negatively correlated with LSaO2,and positively correlated with AHI (P<0.01). 3Serum IGF-1 level[(46.56+/-3.74)MUg/L] increased slightly compared with those before treatment[(42.79+/-4.87)MUg/L] in 30 severe patients after treatment with 3 months CPAP and regimen (P<0.01). Serum IGF-1 level[(56.61+/-5.46)MUg/L] increased significantly after treatment for six months; AHI level (18.72+/-7.36) was significantly lower than that before treatment (48.77+/-10.51), and LSaO2[(87.42+/-8.61)%] increased significantly than that before treatment[(68.33+/-10.24)%].Conclusion:OSAHS patients with decreased serum IGF-1 level may be associated with concurrent insulin resistance. Surgery combined with more than half a year of CPAP treatment can significantly reduce AHI, improve the level of LSaO2 and serum IGF-1. Serum IGF-1 levels could be used as a monitor of efficacy evaluation. PMID- 29798074 TI - [Correlation study between the levels of serum MCP-1,SAA and cognitive function in patients with COPD-OSAHS]. AB - Objective:To study the correlation among the serum monocyte chemoattractant protein-1 (MCP-1),serum amyloid A(SAA) and the level of cognitive function in patients with chronic obstructive pulmonary disease and obstructive sleep apnea hypopnea syndrome overlap syndrome(OS).Method:Sixty patients with OS were in the experimental group, and 33 patients with COPD were in control group. The serum levels of MCP-1 and SAA were measured, and the correlation among MCP-1, SAA and cognitive function was observed by the Montreal scale.Result:1The serum levels of MCP-1 and SAA in OS group were (159.85+/-21.38)ng/L and (122.64+/-42.49)ng/L respectively,which in control group were (135.02+/-15.31)ng/L and (71.37+/ 10.16)ng/L respectively.There were the was statistically significant difference between the two groups(P<0.05). 2Montreal scale score and its sub items in OS group were lower than the control group.The difference was statistically significant (P<0.05).3There was significant negative correlation between Montreal scale and the serum levels of MCP-1(r=-0.654,P<0.05) and SAA (r=-0.617,P<0.05) in OS group.Conclusion:Patients in the OS group had obvious cognitive impairment compared with the ones in control group, which suggested that OSAHS might be an independent risk factor for cognitive impairment. The cognitive function of OS patients was negatively related to MCP-1 and SAA, which suggested that MCP-1 and SAA played a role in the occurrence of cognitive impairment in OS patients. PMID- 29798075 TI - [Perioperative management in chronic rhinosinusitis patients receiving long-term oral warfarin]. AB - Objective:To investigate the safety and validity of endoscopic sinus surgery in chronic rhinosinusitis patients receiving long-term oral warfarin.Method:Fifty eight chronic rhinosinusitis patients receiving long-term oral warfarin were given low-molecular-weight heparin as a bridge therapy. Fifty-eight patients who did not take warfarin were selected as the control group. The intraoperative bleeding volume, operation time, incidence of thrombosis and recurrence rate of sinusitis were observed.Result:The operation time and intraoperative bleeding volume of the experimental group were significantly higher than those of the control group. There were no significant differences of age,gender,thrombosis incidence, nd recurrence between the two groups.Conclusion:Low-molecular-weight heparin is safe and effective bridge therapy to have an endoscopic sinus surgery for the chronic rhinosinusitis patients receiving long-term oral warfarin. PMID- 29798076 TI - [Clinical study of hydrogen-rich saline in the treatment of moderate to severe allergic rhinitis]. AB - Objective:To investigate the effectiveness and safety of nasal lavage with hydrogen-rich saline in the treatment of moderate to severe allergic rhinitis.Method:Twenty patients with moderate to severe persistent allergic rhinitis were treated with normal saline and hydrogen-rich saline lavage the nasal cavity. The study was randomized doubl-blind self-control study. The symptoms and signs score, treatment index and total effective rate were evaluated before and after treatment, and the nasal conjunctivitis related quality of life questionnaire (BQLQ) was used to evaluate the life quality of patients.Result:There were significant differences of the symptoms, signs scores, the treatment index, the total efficiency and BQLQ between the two kinds of lavage fluid used for patients before and after treatment(P<0.05). No significant adverse reactions occurred during follow-up.Conclusion:Hydrogen-enriched saline is safe and effective for allergic rhinitis. PMID- 29798077 TI - [Expression and role of IL-18 in chronic rhinosinusitis]. AB - Objective:To study the expression and role of interleukin-18 (IL-18) in different clinical phenotypes of chronic rhinosinusitis(CRS)and in different subtypes of CRS with nasal polyps (CRSwNP).Method:During nasal endoscopic surgery, inferior turbinates were obtained from 13 patients with nasal septum deviation (control group),uncinate processes were obtained from 10 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and nasal polyp tissues were obtained from 36 patients with CRSwNP, respectively. IL-5 expression in CRSwNP was detected by ELISA, and the expression of IL-18 mRNA and protein in different subtypes of CRS were assessed by real-time PCR, ELISA and immunohistochemistr.Result:CRSwNP was divided into 12 cases of IL-5 positive nasal polyps (IL-5+NP)group and 24 cases of IL-5 negative nasal polyps (IL-5 NP)group. The expression of IL-18 mRNA and protein in all CRSsNP,IL-5+NP and IL-5 NP groups were higher than that in control group (P<0.01 or P<0.05),but no significant difference existed between IL-5+NP and IL-5-NP (P>0.05) group. IL-18 also expresses in epithelial cells of normal nasal mucosa.Conclusion:CRSwNP can be divided into two main subtypes: IL-5+NP and IL-5-NP. The increasing expression of IL-18 in CRSsNP, IL-5+NP and IL-5-NP compared with control group indicates that IL-18 may play a key role in the pathogenesis of CRS, and IL-18 expression in nasal polyps is not affected by the type of inflammation. The possible presence of balance between IL-18 and IL-18 binding protein in normal nasal mucosa provides a new way for research and treatment of CRS. PMID- 29798078 TI - [Multiple-factor analysis of serum allergen distribution of patients with allergic rhinitis and level of main allergen IgE in Shenyang area]. AB - Objective:To discuss multiple-factor analysis of serum allergen distribution of patients with allergic rhinitis and level of main allergen IgE in Shenyang area, and to provide a scientific basis for the prevention of allergic rhinitis in this area.Method:Serum IgE was detected in 749 cases[501 cases of male (66.8%), and 248 cases of female (33.2%)], with allergic rhinitis.The age range was from 3 to 65 years old, and they were divided into 5 groups based on age. A questionnaire survey was conducted to analyze the distribution of serum allergens and to carry out a multiple-factor analysis of level of the main allergen IgE in patients.Result:The primary allergen was house dust mite/dust mite in each age group, and the differences in the positive rate of elm, mold, cat/dog fur scurf, cockroach and ragweed among different groups were statistically significant(P<0.01 or P<0.05).The ingested allergen sequencing for all age groups: the distribution of 7-14 years old group and 15-35 years old group were consistent with that of the whole, among the under 6 years old group, mango and pineapple was ranked 1st,beef and mutton was ranked 2nd,the occurrence rate of shrimp and crab rose to the 3rd place, among the 36-60 years old group, mango, pineapple and milk was ranked 1st, egg was ranked 2nd, and beef and mutton ranked 3rd, the differences in positive rate of mango and pineapple, beef and mutton, crab and nut among all groups were statistically significant(P<0.01 or P<0.05).The IgE level of cockroach was impacted by the allergic history, home cultivation of flowers and plants and animal domestication. The IgE level of mold was impacted by sex, allergy history, home rearing of pet and furniture updates. The IgE level of wormwood was impacted by allergy history and asthma history. The IgE level of peanut was impacted by age and allergy history. The IgE level of egg was impacted by history of food and drink allergy, home cultivation of flowers and plants and home rearing of pet. The IgE level of crab was impacted by the allergy history and home rearing of pet.Conclusion: The primary inhaled allergen in all groups is house dust mite/dust mite, and the ingested allergen varies in each group, which has provided a reference basis for prevention of ingested allergy.The varying influence factors for IgE level of primary allergens could be used to prevent the patients from contacting the allergen,and each risk factor has become a focus of prevention and control for patients, offering a major help to the prevention and treatment of allergic rhinitis. PMID- 29798079 TI - [The application of cattle acelluar dermal matrix xenograft associate with conchoplasty in the open mastoidectomys]. AB - Objective:To study the value of acelluar dermal matrix xenografts associated with conchoplasty in the open mastoidectomy.Method:One hundred and thirty-three cases of chronic otitis media undergoing open mastoidectomy and conchoplasty were enrolled in this study. The effects were analyzed and compared between 70 cases in plastic group repaired by acelluar dermal matrix xenografts and 63 cases in control group.Result:The epithelization time is 28.5d and the dry-ear time is 27.15 d in plastic group. In control group, they were 60.75d and 44.35d respectively. The difference had statistical significanceConclusion:The application of cattle acelluar dermal matrix xenograft associated with conchoplasty in the open mastoidectomy is beneficial to the recovery of the cavity which can shorten mastoid cavity epithelization time, promoting dry ear, reducing postoperative infection and granulation. PMID- 29798080 TI - [The bacteriologic features of recurrent acute rhinosinusitis]. AB - Objective:To investigate the bacteriologic characteristics of recurrent acute rhinosinusitis(RAR).Method:Twenty-nine patients (29 with RAR) from outpatient clinic in our hospital between June 2010 and May 2016 were enrolled in the study. Specimens of the middle meatus or olfactory cleft area using the sinus endoscopy through were transported to the laboratory for bacterial culture.Result:Twenty five specimens out of 29 were bacterial culture positive (culture positive rate was 86.2%).A total of 32 isolates (25 aerobic or facultative and 7 anaerobic) were recovered from the 29 cases of RAR. The predominant aerobic or facultative bacteria were Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. The predominant anaerobic bacteria were Bacteroides fragilis and Propionibacterium. Antibiotic susceptibility tests showed that the resistance rate of these aerobic or facultative bacteria to Macrolides (Erythromycin and Azithromycin) and quinolones (Levofloxacin) was 88% and 92%, respectively. Similarly, the resistance rate of bacteria to beta lactamase antibiotics (penicillin, ampicillin, and cefazolin) was also greater than 90% (100%, 92%, and 92%, respectively). But the drug resistance of these bacteria to the third?generation cephalosporin combined with beta lactamase inhibitors (Cefoperazone/sulbactam) was 20%. Among the 7 strains of anaerobic bacteria, 6 strains were sensitive to ornidazole.Conclusion:The major pathogens of RAR are the aerobic and facultative bacteria Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, most of which are resistant to commonly used antibiotics. PMID- 29798081 TI - [Pathological analysis and treatments of neck infection induced by congenital pyriform sinus fistula]. AB - Objective:To identify the pathogenic bacteria of CPSF and their resistance to antibiotics,and guide the rational use of antibiotics therapy.Method:One hundred and thirty cases of deep neck infection whose imaging finding depicted patients with suspected as CPSF were enrolled in the study from January 2010 to June 2017.Specimens were collected from abscesses or other inflammatory lesions from all patients through a small incision or the external orifice on the skin of the neck.Result:A total of 108 strains of pathogens have been isolated from 88 patients (positive rate: 67.7%), among which the gram-positive bacteria accounted for 56.5%, gram-negative bacteria accounted for 43.5%. Streptococcus and Staphylococcus aureus (22.2%) were the most common pathogens among young patients (<=14 years old) (17.7%);Klebsiellapneumoniae (15.7%) were the most common pathogens among the patients over 14 years old. Separation of pathogenic bacteria have maintained a low resistance to most antibiotics. G+ bacteria is totally sensitive to quinupristin/dalfopristin and vancomycin; G-bacteria is totally sensitive to cefoperazone/Batan, piperacillin/tazobactam,imipenem.Conclusion:Most of pathogens come from upper respiratory tract in CPSF cases, and are mostly sensitive to beta?lactamase. PMID- 29798083 TI - [Analysis of lymph node jump metastasis in papillary thyroid carcinoma]. AB - Objective:To summarize the metastatic feature of lateral neck lymph node metastasis in papillary thyroid carcinoma.Method:Clinical and pathological data were collected from 301 patients who were first diagnosed as PTC in our hospital. These patients were divided into positive and negative status of lateral cervical lymph nodes and lymph node jump metastasis. Chi-square test and Logistic regression analysis were used to evaluate the relationship between lateral cervical lymph node status and clinicopathology.Result:Tumor size over 2cm, Unilateral thyroid gland contains multiple foci,multiple foci, capsular invasion, ultrasound feature of PTC,the main foci located in the isthmus and the pole of gland, trachea/parathyroid lymph nodes positive were associated with the lymph node jump metastasis in papillary thyroid(P<0.05).Conclusion:Multiple foci in single gland, multifocal foci, calcification and the primary tumor involving the superior pole and middle of the thyroid gland are independent influencing factors for skip lateral lymph node metastasis in PTC(P<0.05). PMID- 29798082 TI - [Effects of metformin on papillary thyroid carcinoma in nude rats model]. AB - Objective:To establish an subcutaneous xenotransplanted tumor model of papillary thyroid carcinoma (PTC) and investigate the role of metformin in apoptosis of PTC.Method:Model rats were randomly divided into four groups: control group, Met group and Met+DM group. The tumor volumes were recorded each week. Flow cytometry was used to detect the apoptosis rate of tumor. Immunohistochemistry was used to detect CyclinD1 and the cellular proliferative activity index PCNA and Ki 67.Result:Compared to the control group,there were a significant decrease in tumor volume and antitumor effect in Met and Met+DM groups. The apoptosis rate increased in Met and Met+DM groups. While compared with the control group, the expressions of PCNA,CyclinD1 and Ki-67 significantly decreased in Met and Met+DM groups. There was no difference between Met and Met+DM group.Conclusion:The effect of Metformin on inhibiting tumor growth were related with the imbalance of cell proliferation and apoptosis. PMID- 29798084 TI - [Repair of head and neck malignant tumor after radiotherapy tissue defects by deltopectoral flap]. AB - Objective:To investigate the clinical effect of deltopectoral flap on neck soft tissue defect after radiotherapy of head and neck malignant tumor.Method:Five cases of repair with thoracic peninsula and island skin flap for neck soft tissue defects after radiotherapy were included in the study.Result:All of the five flaps survived successfully. However, two patients had exudation on the incision sutures and 1 case has incision dehiscence. However, the wound was healed with the measure of the shoulder brake and wound resutured. In 1 case, the skin and soft tissue of the lateral neck were necrotic, with the contralateral deltopectoral flap to repair after healing. There were no complications after repair of skin flap in 1 patient.Conclusion:The deltopectoral flap is found as a efficant tissure for repair of head and neck tissue defects after radiotherapy. PMID- 29798085 TI - [Cause analysis of non dry ear after canal wall down mastoidectomy]. AB - Objective:To investigate the possible causes of non dry ear after canal wall down mastoidectomy(CWD).Method:Clinical data of 42 patients undergoing revision CWD in our hospital were analyzed retrospectively,which included history,symptoms,signs,audiological examination,imaging examination, intraoperative findings and postoperative follow-up.All patients underwent CWD and tympanoplasty under general anesthesia.Result:Twenty-six cases were insufficient opened of sinodural angle,36 cases remained mastoid air cell(9 cases is mastoid tip air cell remained),13 cases were inadequate exposured of anterior epitympanic recess, 23 cases were inadequate exposured of posterior tympanum, 25 cases had high facial ridge, posterior facial nerve and labyrinth air cell were 5 cases,3 cases had granulation in round window, 5 cases had dysfunctional eustachian tube, 32 cases had narrow external acoustic meatus. During 3 months,6 months and 1 year follow-up, all 42 cases patients under revision CWD presented with dry ears.Conclusion:Insufficient opened of sinodural angle and mastoid air cell,inadequate exposured of anterior epitympanic recess and posterior tympanum, high facial ridge, narrow external acoustic meatus are all the possible causes of no-dry ear after CWD; As the location of concealment, posterior facial nerve and labyrinth air cell are difficult to clean. The dressing cavity do not be cleaned in time after operation is also the underlying cause of postoperative non-dry ear. PMID- 29798086 TI - [Local combined with systemic glucocorticoid treatment of young and middle-aged patients with severe and profound hearing loss]. AB - Objective:To investigate the clinical effect of local combined with systemic glucocorticoid injection on young and middle-aged patients with severe and profound hearing loss. Method:Ninety-three cases of young and middle-aged patients with severe and profound hearing loss admitted to our hospital from May 2013 to May 2017 were retrospectively analyzed. Patients were divided into two groups according to the different treatment. Forty-six cases in control group were treated with systemic injection of glucocorticoids.Forty-seven cases in observation group were treated with local administration combined with systemic glucocorticoid therapy. The efficacy, changes of average hearing threshold and the incidence of adverse reactions were evaluated.Result:The total effective rate in the observation group was 68.09%, which was significantly higher than that in the control group (45.65%,P<0.05).After treatment, the average hearing thresholds in the observation groups of 0.5,1.0,2.0 and 4.0kHz were(35.77+/-13.28)dB HL,(39.71+/-14.09)dB HL, (32.99+/-10.73)dB HL and (30.17+/-9.29)dB HL respectively,which were significantly higher than that in the control group(26.30+/-14.03)dB HL,(25.14+/-13.28)dB HL,(20.54+/-9.27)dB HL,and (20.98+/ 8.71)dB HL(P<0.05).Among all the patients received systemic injection of dexamethasone sodium phosphate injection,there was no other complications were found except for one patient whose blood pressure instability was relieved after treatment stopping. In the observation group, intratympanic methylprednisolone sodium succinate did not cause serious complications such as tympanic cavity infection and perforation of the tympanic membrane on the basis of systemic injection.While in the observation group,one case complained of earache and one case complained of a slight burning sensation in the ear, and both of them eased after rest.Conclusion:Local combined with systemic glucocorticoid treatment of young and middle-aged patients with severe and profound hearing loss can significantly improve the efficiency and increase the average hearing threshold changes at 0.5,1.0,2.0 and 4.0 kHz,and there was no serious adverse reactions. PMID- 29798087 TI - [The effects of postauricular injection of methylprednisolone on medium-high frequency sudden hearing loss]. AB - Objective:To study the effects of postauricular injection of methylprednisolone on medium-high frequency sudden hearing loss.Method:The data of 45 patients with invalid treatment who were diagnosed as medium-high frequency sudden hearing loss were retrospectively studied. They were divided into postauricular injection group and non-postauricular injection group. The treatment efficiency and hearing improvement at each frequency were compared between the two groups.Result:The improvements of hearing threshold in the non-postauricular injection group were(6.30+/-5.00)dB HL,(3.80+/-5.52)dB HL,(5.35+/-5.50)dB HL,(15.60+/-11.84)dB HL,(19.60+/-13.46)dB HL,(15.40+/-12.90)dB HL at 250, 500, 1000, 2000, 4000 and 8000Hz, respectively. The hearing improvements of the postauricular injection group were (5.35+/-6.22)dB HL,(2.50+/-3.00)dB HL,(4.65+/-6.60)dB HL,(23.75+/ 10.75)dB HL,(25.75+/-11.73)dB HL,(30.50+/-14.50)dB HL at 250, 500,1000,2000,4000 and 8000Hz, respectively. There were significant differences between the two groups in hearing improvements at 2000-8000Hz. The treatment effective rates were 44% and 80% for the non-postauricular injection group and postauricular injection group respectively, which showed a significant difference(chi2=8.385P<0.05).Conclusion:Postauricular injection of methylprednisolone as a remedy treatment is safe and effective for sudden hearing loss in middle and high frequency. PMID- 29798088 TI - [Clinical analysis of combined treatment in 87 patients with recurrent allergic fungal rhinosinusitis]. AB - Objective:To evaluate the effects of combined treatment with FESS on postoperative recurrent allergic fungal rhinosinusitis treatment.Method:Eighty seven patients with allergic fungal sinusitis under combined treatment were investigated.Result:All patients were followed up for more than one year.Clinical symptoms had greatly improved after treatment compared with before treatment.Postoperative VAS score and Lund-Mackay score were lower than preoperative ones.Out of 87 patients,42 patients were successfully cured, 37 patients showed improvement, but there was no change in other 8 patients. The total efficacy rate was 90.81%.Conclusion:The combined treatment of recurrent allergic fungal rhinosinusitis treatment has achieved good effect. We should not only open sinus and remove the fungi, but also should pay attention to the elimination of inflammatory response in the treatment of recurrent allergic fungal rhinosinusitis. PMID- 29798089 TI - [The differences of myringoplasty performed in active and inactive nflammatory stage]. AB - Objective:Through comparing of simple underlay myringoplasty performed in active and inactive inflammatory stage of the chronic otitis media, to explore how the tympanic cavity inflammation affect the outcome of the myringoplasty.Method:Forty six ears were enrolled in active inflammation group (group A,n=46), and 52 ears were enrolled in inactive inflammation group (group B,n=52). All the patients had received the simple underlay technique myringoplasty. The following-up with otoscope and auditory test had been done in post-operative 12 months.Result:There was no statistic difference of gender and age between two groups. The graft taken up rate of the group A was 87,0%, that of group B was 90,4%, and there was no statistic difference between two groups(P>0.05).There was no statistic difference of auditory threshold in pre-operative period(P>0.05) and the ABG closure in post operative period(P>0.05)between two groups. The re-perforation rate of the tympanic membrane also has no difference between two groups(P>0.05).Conclusion:There is no difference of the underlay technique myringoplasty between the active inflammatory stage and inactive inflammatory stage. The active inflammatory condition of the tympanic cavity is not the contraindication of the myringoplasty. PMID- 29798090 TI - [Isolated vertigo as the first symptom of posterior circulation infarction:reporot of 11 cases]. AB - Objective:To analyze the clinical characteristics of patients with cerebellar and brainstem infarction who initially presented with isolated vertigo to avoid misdiagnosing of this disease.Method:Eleven patients with cerebellar and brainstem infarction who initially presented with isolated vertigo treated in our clinic between January 2014 and September 2017 were reviewed and the clinical characteristics and imaging presentation of the patients were evaluated.Result:Vertigo as the first attack was in 5 cases, recurrent attacks was in 6 cases,10 cases were with vascular risk factors except for 1 case, initially diagnosed as vestibular neuritis was 4 cases, Meniere's disease was 1 case, posterior circulartion ischemia was 1 case,and unknown causes was 5 cases; delayed neurological symptoms and signs occurring was 4 cases, but not in other cases; finally determined by brain MRI as acute cerebellar infarction was 5 cases, brainstem infarction was 5 cases, and concurrent cerebellar and brainstem infarction was 1 case. All patients had good prognosis.Conclusion:Isolated vertigo due to posterior circulation infarction is easy to be misdiagnosed as peripheral vertigo.Patients presenting with isolated vertigo, when with vascular risk factors, should receive MRI and DWI examinations. Properly diagnosis and treatment may lead a good prognosis. PMID- 29798091 TI - [Preliminary exploration for recurrent secretory otitis media treatment by balloon dilation Eustachian tuboplasty combined with tympanotomy tube insertion]. PMID- 29798092 TI - [Effect observation of low-temperature plasma radiofrequency ablation under endotoscope in treatment of otitis media with effusion in the adult]. PMID- 29798093 TI - [Nasopharyngeal atypical carcinoid misdiagnosed as a cyst:one case report]. AB - Atypical carcinoid ,a kind of neuroendocrine tumor(NET),rarely shows its malignant manifestations firstly in otorhinolaryngology including atypical clinical features of symptoms such as rapid tumor growth, extensive invasion, high rate of metastasis and poor prognosis. Based on the clinical data of a nasopharyngeal atypical carcinoid patient diagnosed and treated recently in our hospital,a literature review including its biological behavior, diagnosis and treatment methods was present so as to further improve the understanding of such kind of tumor. PMID- 29798094 TI - [Clinical significance and research progress of pepsin in laryngopharygeal reflux and laryngeal carcinoma]. AB - Laryngeal carcinoma is a common malignancy, and the incidence of this disease is on the rise. In recent years, more and more studies of the etiology and risk factors have confirmed the correlation between laryngopharygeal reflux and the incidence of laryngeal carcinoma. Laryngopharygeal reflux is defined as reflux of the stomach contents above the upper esophageal sphincter. Stimulation and injury of acid to the esophagus and throat mucosa have now been studied more thoroughly, and pepsin plays an increasingly important role in laryngopharygeal reflux disease. The incidence of laryngopharygeal reflux in patients with laryngeal carcinoma reported in the literature was 54.0%-88.7%, mainly because of mucosal injury due to the combined effect of gastric acid and pepsin. This article reviews the significance of pepsin in laryngopharygeal reflux, its mechanism of action and related clinical detection methods. PMID- 29798095 TI - [Petrous bone cholesteatoma]. PMID- 29798096 TI - [A randomized controlled trial on short-term efficacy of the modified Semont maneuver for the treatment of posterior canal benign paroxysmal positional vertigo]. AB - Objective:To observe the short-term efficacy of modified Semont maneuver for posterior canal benign paroxysmal positional vertigo (PC-BPPV)Method:This was a prospective randomized controlled trial on 130 PC-BPPV patients. Subjects were randomized divided into two groups: modified Semont (65 patients),and Epley(65 patients).Each maneuver was repeated twice,and the presence of sequelae,nystagmus and vertigo on positional testing were evaluated 3rd day and 1 week after treatment.Result:Five patients were lost to follow up (all five in the modified Semont group),and three patients failed to complete treatment (all three in the Epley group). The sequelae at the 3rd day and one week after modified Semont maneuver were 27 and 9,while 41 and 15 in Epley group. The efficacy rates at the 3rd day and one week after modified Semont maneuver were 91.7% and 98.3%,and 91.9% and 96.8% in Epley group retrospectively. The sequelae and short-term effective rate of patients in modified Semont group was no difference when compared with that in Epley group (P>0.05).Conclusion:Modified Semont maneuver represents a simple rapid and effective approach to the treatment of posterior canal benign paroxysmal positional vertigo. PMID- 29798098 TI - [Study of low frequency release time in WDRC on hearing-impaired individual in mandarin language environment]. AB - Objective:To investigate the influence of low frequency release time of WDRC(wide dynamic range compression)to speech recognition score (SRS) of deaf subjects with hearing aids in mandarin language environment.Method:Release time constants are set differently from the values of 50 ms,100 ms,200 ms,400 ms and 800 ms in low frequency (LF) channel,with 3 kinds of shaped noise,combining a certain LF release time constant with a certain shaped noise forms 15 different groups of experimental conditions. The testing material is mandarin sentences which are the outputs of simulation in the 15 different release time combinations.Result:If the release time is set the value of 400 ms,the patients with hearing aids can get the best mandarin speech intelligibility; the type of babble noise have significant effects on mandarin SRS.Conclusion:Statistical analysis of test results shows that the release time in LF channel or the type of shaped noise trends to influence mandarin SRS. PMID- 29798097 TI - [Different states of otitis media were retrospectively analyzed of myringoplasty]. AB - Objective:Through analysis of the tympanic membrane perforation rate and hearing improvement rate with chronic suppurative otitis media (CSOM) by myringoplasty,to observe the effect of different preoperative conditions such as middle ear lesion,eustachian tube (ET) function and infection status on the postoperative curative effect.Method:Retrospective analysis of EENT Hospital of Fudan University from January 2012 to November 2016 during the 203 cases (203 ears) with clinical data of myringoplasty: according to intraoperative exploration of the presence of purulent secretions in the tympanic cavity,divided into infection active group and infection quiescence group; according to the preoperative results of the function of ET with acoustic impedance test divided into dysfunction or good group; according to the preoperative temporal bone HRCT suggested that the middle ear (mastoid cells,tympanic antrum and tympanic cavity) with or without soft tissue density,divided into the group with no focal lesion and the group with focal lesion. Review endoscopy and pure tone audiometry after 3 to 6 months. Using SPSS 19.0 statistical software to compare the differences among them of tympanic membrane perforation rate and hearing improvement rate.Result:Single factor analysis: 1The infection quiescence group of tympanic membrane perforation rate was 11.93%(13/109),higher than the infection active group [8.51%(8/94)]; the infection quiescence group of hearing improvement rate was 75.23%(82/109),below the infection active group [79.79%(75/94)],no statistically significant differences of them (P>0.05).2The group with dysfunction of ET of tympanic membrane perforation rate was 14.06%(9/64),significantly higher than the group[4.04%(4/99)]with good function ET,with statistical difference of them (P<0.05); the group with dysfunction of ET of hearing improvement rate was 76.56% (49/64),lower than the group[81.82%(81/99)]with good function of ET,no significant difference of them (P>0.05).3The group with no obvious lesion of tympanic membrane perforation rate was 9.09% (10/110),lower than the group [11.83%(11/93)]with focal lesion; the group with no obvious lesion of hearing improvement rate was 78.18% (86/110),higher than the group with focal lesion [76.34%(71/93)],no significant difference of them (P>0.05).Multivariate analysis: 1There was a significant correlation of postop-erative tympanic membrane perforation rate with preoperative ET functi-on (P<0.05).There was no significant correlation of the postoperative tympanic membrane perforation rate with the infection status and the temporal bone HRCT images in the middle ear lesions (P>0.05).2There was no significant correlation of the postoperative hearing improvement rate with the infection status,the ET function and the temporal bone HRCT images in the middle ear lesions (P>0.05).Conclusion:Dysfunction of ET and localized lesions of the ear were more common in infection active;the accumulation of purulent exudate on the surface of the tympanic mucosa and localized lesions of the middle ear did not affect the healing rate of the tympanic membrane and the hearing improvement rate; ET function is one of the most important factors that affect the healing rate of tympanic membrane after operation,the patients with ET dysfunction are more likely to affect tympanic membrane perforation,but does not affect the hearing improvement rate. PMID- 29798099 TI - [The exploration of VEGF-B methylation in the nasal polyp]. AB - Objective:The objective of this study is to investigate the methylation status of vascular endothelial cell growth factor B (VEGF-B) gene and to indentify the roles in pathogenesis,development and classification of nasal polyps.Method:The methylation status of VEGF-B gene of 28 nasal polyp tissues and 12 samples of inferior turbinate tissues were detected by methylationspecific-polymerase chain reaction (MS-PCR) and gene sequencing.Result:There was significant statistic diference between nasal polyp tissue group and control group (chi 2=4.096,P<0.05). The results of gene sequencing suggest that the VEGF-B gene promoter were hypomethylation status in the nasal polyps.Conclusion:Methylation status of VEGF-B promoter may play an important role in the pathogenetic mechanism of nasal polyps. PMID- 29798100 TI - [Prevalence and risk factors of allergic rhinitis: a Meta-analysis]. AB - Objective:To clarify the morbidity and risk factors of allergic rhinitis (AR) in China so as to provide scientific basis for prevention of AR in the relevant populations.Method:Pubmed,Embase,Web of science,Cochrane Library,CNKI,VIP,Wanfang Data,CBM databases were searched for associated studies. The prevalence and risk factors of AR in China were retrieved from individual studies and the pooled estimates generated by R3.2.3 software.Result:Thirty-one cross-sectional studies were included in the Meta-analysis. The results indicated that the incidences of AR in Chinese children were 15.79%(95%CI 15.13-16.45).The highest prevalence is 17.20% in central China,the lowest is 13.94% in eastern China. The incidences of AR in Chinese adult were 13.26% (95%CI 12.05-14.47).The highest prevalence is 15.45% in southern China,the lowest is 10.93% in southwestern China. The pooled odds ratio (OR) values of family history (5.40),dust exposure history (2.04),drug allergy history (2.83),history of asthma(4.45),environmental tobacco smoking(ETS)(2.00),water damage (1.50),upholstering(1.41),pollen allergy(17.18),molds(1.31),keeping pets (1.29),cockroach (1.69).Conclusion:A study on the epidemic tendency of AR in China showed the morbidity of AR in Chinese children is higher than adult. Moreover,prevalence vary from region to region. Eleven kinds of risk factors mentioned above play imperative roles in the pathogenesis of AR. The early interventions which are associated with risk factors should be implemented in AR. PMID- 29798101 TI - [Application of MDCT and post-processing in children with tracheal foreign body]. AB - Objective:To explore the clinical value of MDCT and post-processing in children with suspected foreign body in trachea.Method:Two hundred patients with suspected tracheal foreign body were treated with 64-slice spiral CT (MDCT) and simulated endoscopic imaging,then compared with seen in bronchoscopy; Compare the results of MDCT and post-processing with the coincidence of intraoperative findings.Result:One hundred and eighty-four cases of positive children were examined by MDCT postprocessing technique and bronchoscopy,179 cases were obstructed by exogenous foreign body,5 cases were phlegm thrombosis (endogenous foreign body) obstruction; 16 cases of children with no foreign body diagnosed by MDCT post-processing technique were also examined by bronchoscopy. The results showed that there was a foreign body in 1 case,and the foreign body was located in the pharyngeal cleft (watermelon spermoderm),and the remaining 15 cases had no foreign body. MDCT and post-treatment techniques for children with tracheal foreign body diagnosis of 99.4% sensitivity,specificity of 75%.There was no significant difference in the detection rate of foreign body between the two techniques of MDCT and post-processing technique and bronchoscopy (P>0.05). Examed by MDCT and post?processing,we can understand the specific location and size of foreign body,nature,shape preoperatively.Conclusion:Although MDCT and post-processing techniques can not be used to treat tracheal foreign bodies,but the diagnostic rate of bronchial foreign bodies is comparable to that of bronchoscopy. We could apply MDCT examination and post processing before the bronchoscopy,for foreign body inhalation history is not clear,or suspected airway foreign body. We can improve the level of diagnosis and treatment through guiding the operation of bronchoscopy focus. PMID- 29798102 TI - [Experimental study of using chitosan nerve conduit combined with PRP to repair facial nerve defect]. AB - Objective:The purpose of this study was to produce chitosan nerve conduit in order to investigate the feasibility of chitosan nerve conduit combined with autologous platelet-rich plasma (PRP) for repairing facial nerve defects.Method:Forty New Zealand white rabbits were randomly divided into four groups (n=10 in each group).Establishment of the facial nerve defect model of the upper buccal branches was placed in the nerve regeneration catheter and injected with the same amount of PRP and saline. The PRP was injected into the chitosan nerve conduit as group A. The physiological saline was injected into the chitosan nerve conduit as group B. The physiological saline was injected into the silicone tube as group C. The PRP was injected into the silicone tube as group D. Eight weeks later,facial nerve gross observation,facial nerve electrophysiological tests,histological observation,image analysis,valuation of nerve regeneration recovery were detected.Result:Five patients were lost to follow up (all five in the modified Semont group),and three patients failed to complete treatment (all three in the Epley group). The sequelae at the 3rd day and one week after modified Semont maneuver were 27 and 9,while 41 and 15 in Epley group. The efficacy rates at the 3rd day and one week after modified Semont maneuver were 91.7% and 98.3%,and 91.9% and 96.8% in Epley group retrospectively. The sequelae and short-term effective rate of patients in modified Semont group was no difference when compared with that in Epley group (P>0.05).Conclusion:The chitosan nerve conduit combined with PRP has a certain effect on the repair of facial nerve defects and is expected to be applied to the repair of clinical facial nerve defects. PMID- 29798103 TI - [A study of the curative effect of endoscopic-assisted posterior nasal neurotomy on patients with moderate severe persistent allergic rhinitis]. AB - Objective:To investigate the feasibility and effect of endoscopic-assisted posterior nasal neurotomy on patients with moderate-severe persistent allergic rhinitis (AR).Method:Endoscopic-assisted posterior nasal neurotomy were operated on 32 moderate-severe persistent AR patients who were insensitive to drugs and desensitization treatment,and curative effect were evaluated by scoring according to the diagnosis and curative effect evaluation standard of AR.Result:Follow-up evaluations were perfected after one year. Among them 17 cases were markedly effective,15 cases were effective,and the rate of total effective was 100%,without complications such as nose bleeds,dry eye,etc.Conclusion:The advantages of endoscopic-assisted posterior nasal neurotomy on moderate-severe persistent allergic rhinitis patients include the localization of posterior nasal nerve is clear,easy to operate,the short-term effect is remarkable,and less complications,therefore it's worth using on the AR patients who are failing in drugs and specific immune treatment. PMID- 29798104 TI - [The features of c/oVEMP in patient with unilateral Meniere's disease]. AB - Objective:To evaluate the difference in c/oVEMPs between patients with MD and normal controls.Method:Twenty-two patients with unilateral MD and 21 healthy subjects (as normal controls) were prospectively examined with c/oVEMPs. The results were compared between these two groups. MD group were divided into two groups according to the pure tone average threshold: group1 PTA<=40 dBnHL,group2 PTA>40 dBnHL,and then compared their results. A commercially available software package SPSS 19.0 was used for statistical analysis.Result:The latency and amplitude of cVEMP and oVEMP in the affected side and contralateral side of the MD group were no significant difference. Compared with normal controls,the latency of P1 and N1 was prolonged,the amplitude was decreased in the MD group's cVEMP. The amplitude was decreased in the MD group's oVEMP,but the latency was not prolonged. Group 2's extraction rate of cVEMP was significantly lower than group 1.Conclusion:An increased occurrence of abnormal c/oVEMP recordings appeared in MD patients,possibly as a result of hydrops of the otolith. The saccular dysfunction may be more common than utricular dysfunction. Furthermore,that otolith damage is gradually increasing with the aggravation of cochlear injury in MD. PMID- 29798105 TI - [Clinical analysis of chronic tonsillitis in 12 HIV/AIDS patients]. AB - Objective:To explore the clinical characteristics and efficacy of chronic tonsillitis in HIV/AIDS patients.Method:Clinical features and effects were retrospectively analyzed in 12 HIV/AIDS cases with chronic tonsillitisin.Result:All subjects were men with an average age of(26.4+/ 8.7)years; the common clinical symptoms included sore throat(12/12),fever(7/12),snoring(6/10); tosils in these patients were most frequently found in III grade enlargement (9/12); 11 patients who were performed tonsillectomy,were satisfied with having chosen tonsillectomy with a mean score of(9.5+/-0.8),sore throat episodes and snoring were disengaged after operation in 10 cases,sore throat episodes was significantly improved from 12/year to 2/year in 1 case.Conclusion:Chronic tonsillitis in HIV/AIDS patients occurred more in young and middle-aged men with typical clinical manifestations of sore throat,fever and snoring. Under strict indication,tonsillectomy is an effective treatment for chronic tonsillitis in HIV/AIDS patients. PMID- 29798107 TI - [Clinic effects observation of glucocorticoid inhalation nebulization treating children with secretory otitis media]. PMID- 29798106 TI - [Analysis of olfactory dysfunction after endoscopic and microscopic endonasal transsphenoidal surgery for pituitary adenoma]. AB - Objective:To analyze the clinical data of patients with olfactory dysfunction after endoscopic or microscopic endonasal transsphenoidal approach,and to screen out the possible related factors,to guide clinical diagnosis and treatment,and to improve the patients' quality of life.Method:In the retrospective study,we analyze patients' data,and follow up them with telephone,records the olfactory levels before and after surgery. In the prospective study,five odors were applied to test the olfactory function before the surgery,then one week,3 weeks and 6 weeks after that. The results were statistically analyzed.Result:In the retrospective study,olfactory dysfunction occurred in 67.74%,47.37%in MTS group and ETS group. The olfactory disorder had no significant difference (P>0.05) among MTS group and ETS group after surgery. And the analysis of factors showed no significant difference. In the prospective study,there is significant difference between the preoperative results and postoperative results about the operative side and nonoperative side in ETS group and MTS group (P<0.05). In all results,there is no significant difference between operative side and nonoperative side in ETS group and MTS group (P>0.05).Conclusion:There is olfactory dysfunction after transsphenoidal surgery to resect pituitary adenomas. To prepare the nasal condition well preoperatively,protect the nasal structure intraoperatively and aplicate appropriate treatment postoperatively may reduce the incidence of olfactory disorder. PMID- 29798108 TI - [Clinical diagnosis and treatment for button battery in esophagus in children]. PMID- 29798110 TI - [Synovial sarcoma of infratemporal fossa and pterygopalatine involving maxillary sinus 1 case and the literature review]. AB - We report a case which involves the maxillary sinus by original of synovial sarcoma of infratemporal fossa and pterygopalatine. A 40-years-old man presented with a history of tumor under the earlobe. It is derived from the synovial sarcoma under temporal fossa after tumor excision. The patient is limited to open his mouth and nasal obstruction. The nasal pathologic examination consider synovial sarcoma.We report the case to improve doctors' comprehension of its pathogenesis,clinical manifestations,teeatment and prognosis. PMID- 29798109 TI - [Neurosyphilis and HIV co-infection with the initial symptom of sudden deafness and optic atrophy: a case report]. AB - A 46-year-old male presented with left ear hearing loss,vertigo,tinnitus and left eye blurred vision. Pure tone audiometry showed left ear had been total deafness. Treponema pallidum particle agglutination (TPPA) assay was reactive. The serum rapid plasma regain (RPR) was 1?16. Human immunodeficiency virus(HIV) 1/2 antibody immunoassay was positive,and the CD4 cell count was low at 100 cells/MUl. Cerebrospinal fluid (CSF) TPPA was positive,with a white blood cell count of 53*10 6 /L and protein level of 1.08 g/L.The diagnosis was:1left ear sudden deafness(total deafness type);2neurosyphilis;3acquired immune deficiency syndrome(AIDS). PMID- 29798111 TI - [Surgical treatment progress of OSAHS with multiplane obstruction]. AB - For OSAHS patients with multiplane obstruction,the surgery aimed to single-plane can not receive satisfactory results,while perioperative risks increased significantly. In this paper,in order to provide safe and effective diagnosis and treatment strategies,the assessment,the surgical treatments and effects of different obstructive planes are reviewed. PMID- 29798112 TI - [Progress of sino-nasal IgG4-related disease]. AB - IgG4-related disease is a newly recognized systemic fibro inflammatory disorder that affects the sino-nasal region. It is a rare and emerging entity that can present with bony and soft-tissue invasion,the final diagnosis of this disease mainly depends on pathological examination and majority of patients receiving corticosteroids responded very well to treatment. Thus,Our goal was to highlight the sino-nasal presentation of this unique disease and to review previously reported cases from 2010 to 2016.We hope that clinical physicians to enhance understanding of the disease in order to ensure early diagnosis and early intervention to prevent serious injury and fibrosis of organs. PMID- 29798113 TI - [Research progress and significance of sleep apnea biomarkers]. AB - To review the application of proteomics and metabolomics in the study of OSAHS biomarkers,and to open a new perspective for the study of OSAHS. At present,these studies are still in a very preliminary stage,the results are not always consistent,and far from the clinical application requirements. However,compared with traditional chemical methods,quantitative protein and metabolomics methods still have many advantages and have great clinical potential. Further studies of larger populations for more detailed grouping in the future are necessary to validate these results,and a more structured investigation in cell and animal models is necessary to determine their molecular mechanisms. In addition,the combination of different analytical platforms will be the ideal method for OSAHS biomarker research. In conclusion,the proteomics and metabolomics methods help us to better understand the potential mechanisms of OSAHS and to discover and develop personalized screening,diagnosis,prognostic and therapeutic strategies for future research. PMID- 29798114 TI - [The characteristics of CT scan and MRI images of middle ear adenomas]. AB - Objective:To analyze characteristics of CT scan and MRI images of middle ear adenomas,and provide pre-operation diagnosis and differential diagnosis combined with clinical manifestation.Method:Retrospective analysis of 8 cases of middle ear adenomas which were diagnosed and treated with surgery in Beijing Tongren Hospital between 2004 and 2014, patients' complain, clinical manifestation, physical examination, pure tone analysis, CT scan and MRI images were collected.Result:A total of 8 cases were included in this study with 5 females and 3 males. Age of onset ranged from 21 to 51 years old, with an average age of 37.5 years old, and middle age of 37 years old. All patients suffered from single side middle ear adenomas, 5 of left side and 3 of right side. All 8 patients suffered from hearing loss with tinnitus or stuffy feelings, 2 cases with otalgia, 1 with facial nerve paralysis. Physical examination showed 5 cases of bulging of tympanic membrane, 2 cases of out growth of mass into the external ear canal, and 1 with normal tympanic membrane. CT scan of 7 patients showed mass in tympanum and mastoid, with packaged ossicular chain and with no significant bone damage. 2 cases showed out growth of mass into the external ear canal, and 1 case showed limited mass in middle tympanum. MRI images of 5 cases showed equal T1 and T2 signals with intensifying in tympanum. Long T1 or equal T1 and long T2 signal in mastoid showed obstructive inflammation.Conclusion:Characters of middle ear adenomas includes mass in tympanum without bone damage in CT scan, and equal T1 and T2 signal with significant intensifying in tympanum in MRI images. Combined with clinical manifestation, this radiological information may provide benefit for pre-operation diagnosis. PMID- 29798115 TI - [Functional rhinoplasty under nasal endoscope]. AB - Objective:At different times and cultural background,people have different definition of beauty.With the improvement of economic level and culture quality,people are becoming more and more recognition of nasal appearance and function are equally important.Even the importance of the function of the nasal is higher than the importance of shape of the nose. Concurrent rhinoplasty (nasal dorsum and lateral nasal wall reduction) and functional sinus surgery (nasal septum reconstructory, middle turbinate,inferior turbinate surgery even extended to the nasal cavity expansion tecunhnique, sinusitis surgery) with endoscopic surgical surgical methods were discussed.Method:The study included 20 patients with deformed functional endoscopic rhinoplasty, 2010-2015 in Beijing Tongren Hospital,of ages 16-53, male 14 cases,female 6 cases, 11cases had history of trauma, all of 20 patients have unilateral nasal plugging. Operating methods, 17 patients were performed nasal endoscopic septoplasty and rhinoplasty at the same time. One case cocurrent endoscopic rhinodacryocystostomy.Two cases were performed Nasal endoscopic sinus operation. Only 5 cases use silica gel prosthesis, 15 cases use autologous cartilage in functional rhinoplasty.Result:Twenty patients compared with performed rhinoplasty,nasal septum reconstructory,middle turbinate,inferior turbinate surgery,nasal cavity expansion,sinusitis surgery separately,surgery is better,no other complicationgs occurred.Actually decredsed the number of surgical treatment and hospitalization expenses.Conclusion:Functional endoscopic rhinoplasty,over the same period it solved the nasal shape and nasal ventilation function.To avoid impact on ventilation function in the process of the rhinoplasty.Implements the unification of beauty and function.Reduce the surgical treatment of times and cost.No other complication compared to convertional surgery,high feasibility. PMID- 29798116 TI - [Research on activity evolution of cerebral cortex and hearing rehabilitation of congenitally deaf children after cochlear implant]. AB - Objective:There is a significant difference in the hearing rehabilitation between the congenitally deaf children after cochlear implant(CI). The intrinsic mechanism that affects the hearing rehabilitation in patients was discussed from the perspective of evoked EEG source activity.Method:Firstly, we collected the ERP data from 23 patients and 10 control group children during 0, 3, 6, 9 and 12 months after CI. According to the hearing rehabilitation during 12 months after CI, the patients were divided into two groups: rehabilitation of "the good" and "the poor". Then we used sLORETA to show the changes in the groups of patients' cerebral cortex and compared with the control group.Result:Cross-modal reorganization of cerebral cortex exists in the congenitally deaf children. The cross-modal reorganization gradually degraded and the activity of the relevant cortex followed by normally after CI. There was a statistically significant difference(P < 0.05) in the temporal lobe and the associated cortex around parietal lobe between "the good" and "the poor" groups after 12 months.Conclusion:The normalization of the cross-modal reorganization in patients reflects the hearing rehabilitation after CI, especially the normalization of the activity of the temporal lobe and the associated cortex around parietal lobe, which influences the rehabilitation effect of the auditory function to some extent. This research demonstrated the detection of the mechanism has important significance for the hearing recovery training and evaluation of the hearing rehabilitation after CI. PMID- 29798117 TI - [Clinical curative effect analysis of postauricular topical injection combining with oral hormone in the treatment of the flat type of sudden hearing loss]. AB - Objective:To analyze the clinical curative effect of postauricular topical injection combining with oral hormone in the treatment of the flat type of sudden hearing loss.Method:Data of 128 patients with the Sudden hearing lossfrom year 2015 till now were collected, and randomly divided into two groups: postauricular topical injection group (methylprednisolone sodium succinatefor injection 40 mg+linocaine 2.5 ml, retroauricular groove topical injection, qod, combining with taking methylprednisolone tablets 24 mg in the morning for 3 days) and non postauricular injection group (take methylprednisolone tablets 24 mg in the morning for 3 days). Use SPSS 17.0 software to analyze the hearing curativeeffect of these two groups statistically.Result:The cure rate of postauricular injection group: 23.4%(15 cases), effect appear: 14.1%(9 cases), valid: 37.5%(24 cases), invalid:25.0%(16 cases), total effective rate:75%(48/64).The difference compare of these two group has a statistically significant (P< 0.05).2The cure rate of the flat type patients with the postauricular injection treatment among the total 64 cases is 23.4%, which is higher than the patients without the postauricular injection treatment.The difference compare of these two group has a statistically significant (P< 0.05).3The incrementsof the postauricular injection group in 250 8 000 Hz, which is divided into7different frequencies, from low to high, are (26.48+/-6.23)dBHL, (23.24+/-4.21)dBHL, (21.89+/-7.34)dBHL, (26.07+/-7.01)dBHL, (25.75+/-5.14)dBHL.The mean value compare of frequency 250-500 Hz and 250-4 000 Hz of these two group has a statistically significant (P< 0.05).Conclusion:The curative effect of postauricular topical injection combining with oral hormone in the treatment of the flat type of sudden hearing loss is better than only oral hormone. PMID- 29798118 TI - [Efficacy analysis of psychological intervention on the basis of medication for the treatment of moderate-severe persistent allergic rhinitis]. AB - Objective:To observe the effect of psychological intervention on the basis of drug therapy for moderate-severe persistent allergic rhinitis.Method:Sixty patients with moderate-severe persistent allergic rhinitis were randomly divided into two groups: control group and study group. The control group was only given pure drug therapy. The study group was given drug treatment and psychological intervention. Both groups were treated for 12 weeks. Before and after the treatment, the patients were graded by SAS, SDS and RQLQ to assess their anxiety and depression, as well as changes in the quality of life. Finally, a statistical analysis was performed.Result:After the treatment, the SAS and SDS scores of the control group and the study group were lower than those scores before treatment, and the difference was statistically significant (P<0.05). The SAS and SDS scores were lower in the study group than in the control group after treatment, and the difference was statistically significant (P<0.05).After the treatment, the scores of RQLQ in the control group and the study group were lower than those scores before treatment. and the difference was statistically significant (P<0.05). After treatment with two regimens, the scores of the sleep, the non-nose/eye symptoms, and the emotion were lower in the study group than those scores in the control group, and the difference was statistically significant (P<0.05).Conclusion:To improve the mental disorder and the quality of life of the moderate-severe persistent allergic rhinitis patients, on the basis of drug treatment along with psychological intervention is more effective than using medical treatment. PMID- 29798119 TI - [Role of sleep apnea monitoring management platform in the treatment of patients with obstructive sleep apnea hypopnea syndrome]. AB - Objective:To investigate the clinical significance and value of the sleep apnea monitoring management platform in the treatment of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) by comparing with the traditional continuous positive airway pressure (CPAP) card reader mode.Method:A total of 48 severe adult OSAHS patients from Department of Otorhinolaryngology Head and Neck Surgery-Sleep Medical Center of the Third People's Hospital of Honghe during the period of Nov. 2015 to Aug. 2016 were collected in this prospective study. All of them were diagnosed by PSG and treated with nasal continuous positive airway pressure. They were randomly divided into group A (n=24) and group B (n=24). Group A and B were treated with the traditional CPAP card reader mode and the sleep apnea monitoring management platform respectively. During the follow-up, the compliance, mean blood oxygen saturation, titration pressure, Epworth sleepiness scale after 1, 3, 6 and 12 month treatment were compared between two groups. Ttest was used to analyze the difference. Statistical significance was set at P <0.05.Result:Statistical analysis showed that there were significant difference in the compliance of using CPAP, mean blood oxygen saturation and Epworth sleepiness scale score between the two groups (P < 0.05), but the titration pressure had no difference between the two groups (P>0.05).Conclusion:Compared the sleep apnea monitoring management platform with traditional CPAP card reader mode in the treatment of OSAHS patients, the former could solve the problems during the CPAP use in time, improve the compliance of using CPAP, and which could increase the efficacy of CPAP. Thus, the sleep apnea monitoring management platform is of more clinical value and deserve promotion. PMID- 29798120 TI - [Clinical observation of saccharomyces boulardii combined with cetirizine hydrochloride in children allergic rhinitis]. AB - Objective:To study the treatment efficacy of Saccharomyces boulardii combined with Cetirizine Hydrochloride of children with allergic rhinitis (AR) and the influence of IFN-gamma and interleukin-4 (IL-4) Level in serum.Method:Ninty cases of children were randomly divided into observation group and control group (both n=45).The control group with levocetirizine hydrochloride drops, 5 mL/time for 2 6 years old, 10 mL/time for >6 years old , qd oral. Group based on the combination of Saccharomyces boulardi, 0.25 g/time for <3 years old, qd, > 3 years old, 0.25 g, bid. Four weeks for a course of treatment, and set 30 cases for the health group.Result:The level of serum IFN-gamma was significantly lower in the two groups than in the healthy group (P < 0.01), while the level of IL-4 was significantly higher than that of the healthy group (P < 0.01). After treatment, the levels of IFN-gamma of both groups were up-regulated And the level of IL-4 were down-regulated , but the effect of the treatment group was more obvious (P < 0.01). The total effective rate was 91.11% in the observation group, which was significantly higher than that in the control group (68.89%,chi2=6.94, P < 0.01). After treatment, the symptom scores of the two groups were lower than those before treatment, but the observation group was significantly lower than the control group (P < 0.01). Compared with the control group, the observation group was significantly better than the control group (P < 0.01).Conclusion:The combination of Saccharomyces boulardi and levocetirine hydrochloride in the treatment of children with AR has obvious clinical efficacy, and its mechanism may be related to the correction of interferon IFN-gamma and IL-4. PMID- 29798121 TI - [Clinicopathologic analysis of extranodal non-hodgkin lymphoma of the sinonasal cavities: a 15-case report]. AB - Objective:To investigate the clinical manifestation, imaging and histological features of different histological subtypes of non-Hodgkin's lymphoma of nasal cavity and paranasal sinuses.Method:Fifteen NHL patients of the sinonasal region were collected from the Department of Otolaryngology of Peking University Third Hospital from 2010 to 2016. HE staining and immunohistochemical staining were performed. The clinical characteristics and imaging features of different subtypes were described and analyzed.Result::We analyzed a total of 6 patients with localized sinonasal diffuse large B cell lymphoma and 9 patients with localized sinonasal extranodal NK/T cell lymphoma. The age distribution for these two subtypes is very distinct. The median age of the patients with localized sinonasal extranodal NK/T cell lymphoma was 39 years. There were 5 males and 4 females. Nine sinonasal NHLs were NK/T-cell lymphoma, nasal type, all of which were infected with EBV. The median age of the patients with localized sinonasal diffuse large B cell lymphoma was 64 years. There were 3males and 3 females. Symptoms for patients with SN-DLBCL and SN-ENKTL were significantly different in epiphora, proptosis, diplopia and nasal congestion (P=0.18, 0.004, 0.18, 0.18). Imaging features for patients with SN-DLBCL and SN-ENKTL were significantly different in tumor extended to orbit and inferior turbinate (P>0.05). Positive staining for CD 56 was detected in 9 patients, for CD 3 in 9 patients, for EBER in 9 patients. The Hans algorithm identified 1 patient with the germinal center B cell (GCB) subtype and 5 with the non-GCB subtype.Compared with the control group, the observation group was significantly better than the control group (P < 0.01).Conclusion:Early symptoms of epiphora, proptosis, diplopia, and images finding with orbital invasion should be highly suspected of diffuse large B cell lymphoma. Positive staining for CD 56 and EBER were detected in all patients with extranodal NK/T cell lymphoma, and positive staining for CD20 was detected in all patients with SN-DLBCL. PMID- 29798122 TI - [The clinical study of olfactory dysfunction in IgG4-related disease]. AB - Objective:IgG4-related disease is a newly recognized systemic disease, and its elucidation is progressing. However, little is known about its sinonasal manifestations.The aim of this study was to assess the olfaction of patients with IgG4-related disease.Method:Twenty-two patients with IgG4-related disease underwent the odor stick identification test to measure olfactory function.We analyzed the clinical features, including serum IgG4 levels, involved organs, and sinonasal computed tomography scores to explore the etiology of olfactory dysfunction.Result:Eleven patients with IgG4-related disease were found to have olfactory dysfunction. There were no differences in the clinical features between the olfactory dysfunction group and the normal group.Conclusion:There were no correlation between olfactory function and serum IgG4 level, involved organs or sinonasal computed tomography scores.We found that the prevalence of olfactory dysfunction was high in patients with IgG4-related disease and that it could be reversed.Olfactory dysfunction appears to be a novel important manifestation of IgG4-related disease. PMID- 29798123 TI - [To observe the effect of "Fangfenggubenkeli" on IL-4, IL-5, IL-10 and IFN-gamma cytokines in PBMC supernatant of allergic rhinitis patients with lung depression and spleen efficiency]. AB - Objective:To observe the effect of "Fangfenggubenkeli" on IL-4, IL-5, IL-10 and IFN-gamma cytokines in PBMC supernatant of allergic rhinitis' patients with lung depression and spleen deficiency.Method:One hundred patients were randomly divided into two groups. The treatment group of 50 cases, was given to ancient side of the "Fangfenggubenkeli". The control group of 50 patients, was given to cetirizine hydrochloride, oral treatment. The levels of IL-4, IL-5, IL-10 and IFN gamma in the two groups were measured before and after treatment of 1 month. The changes of the laboratory indexes were compared between the two groups before and after treatment.Result:The levels of IL-4 in the two groups were significantly lower than those before treatment (P < 0.01), and the levels of IFN-gamma were significantly higher than those before treatment (P < 0.01), there was a statistically significant difference.Conclusion:The mechanism of "Fangfenggubenkeli" in patients with allergic rhinitis with lung depression may be related to the IFN-gamma level, lower IL-4 level. Thereby Fangfenggubenkeli would improved the Th1/Th2 imbalance state as a whole. PMID- 29798124 TI - [Clinical application of modified global osteitis score in chronic rhinosinusitis]. AB - Objective:To compare GOSS and a newly proposed modified scoring system for assessment of CRS with osteitis.Method:Seventy-one CRS patients were enrolled prospectively.Their preoperative computed tomography (CT) were assessed for severity and extent of osteitis by two otolaryngologists using OsiriX DICOM Viewer software. The method of measurement was similar with GOSS, which retained scoring maxillary and sphenoid, producing a modified global osteitis score(rang: 0-20). Collected the history and completed VAS, SNOT-22, Lund-Kennedy, Lund Mackay in preoperative. Postoperative follow-up mounted up to 12 months and evaluating CRS patients' outcome. Compared for test-retest and inter-rater reliability between the modified system and GOSS.Result:There is a significant linear positive correlation between Modified GOSS score and GOSS(r=0.913,P<0.001).And Modified GOSS had more association with pre and postoperative L-M and L-K scores than GOSS (r=0.316, 0.357). The modified GOSS showed the highest inter-rater and test-retest, interclass correlation coefficient (pre-ICC=0.947; post-ICC=0.943).Conclusion:Modified GOSS may be a more suitable and convenient scoring system for clinical practice to grading osteitis. PMID- 29798125 TI - [Relationship of symptoms with sleep-stage abnormalities in obstructive sleep apnea-hypopnea syndrome]. AB - Objective:To study the relationship between symptoms and sleep staging in OSAHS patients.Method:A cross-sectional study. Adult subjects who attended a sleep laboratory for diagnostic polysomnography for a period of 1 month were recruited consecutively.OSAHS was diagnosed using American Academy of Sleep Medicine criteria.Subjects filled a questionnaire for symptoms prior to polysomnography.Result:Thirty subjects, of whom 83.3% were obese, met diagnostic criteria, with males constituting 46.7% and females constituting 53%.Mean age was (53.40+/-11.60) years.Sleep architecture comprised N1 (19.50+/-19.00)%, N2 (53.93+/-13.39)%,N3 (3.90+/-19.50)%, and rapid eye movement (8.92+/ 6.21)%.Excessive fatigue or sleepiness, waking up tired, falling asleep during the day, trouble paying attention, snoring and insomnia were significantly related to decreased N3 sleep.Conclusion:Most of the symptoms in OSAHS in adults are related to decreased stage N3 sleep.If confirmed by larger controlled studies, correcting N3 sleep deficiency by pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy to alleviate symptoms. PMID- 29798126 TI - [Role of Testin in nasopharyngeal squamous cancer with high ability of metastasis]. AB - Objective:To explore the influence and regulatory mechanism of TES gene on proliferation and migration of nasopharyngeal squamous cancer(NSPC) 5-8F cell.Method:DNA fragment encoding TES was obtained by RT-PCR method from the human highly metastatic nasopharyngeal squamous carcinoma cell line 5-8F. we identified the recombinant plasmid pEGFP-N1-TES by RT-PCR and DAN sequencing. we stablely transfected the pEGFP-N1-TES into the human highly metastatic nasopharyngeal squamous carcinoma cell line 5-8F, and detected the expression of TES by the RT-PCR and Western-blot method. And detected the impact of 5-8F cells transfection by flow cytometry and scratch tests.Result:Flow cytometry analysis showed that the apoptotic in 5-8F/pEGFP- N1-TES was significantly higher than non transected TES and 5-8F/pEGFP-N1,and the differences were statistically significant(P<0.05).Cell scratch experiments showed that the 5-8F/pEGFP-N1-TES group cell migration rate was obviously lower than non?transected TES and 5 8F/pEGFP-N1 group in the first 12 h, 24 h and 48 h.The difference was significant(P<0.01).Conclusion:The stable transfectant cell model was established successfully. TES in vitro could significantly increase apoptosis and reduce the athletic ability. And thus TES gene might be a novel candidate of tumor suppressor. PMID- 29798127 TI - [Effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome]. AB - Objective:To study effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome.Method:One hundred and twelve patients with asthma were selected from department of respiration, Affiliated Hospital of North China University of science and technology from January 2016 to 2017 in March. Eighty-four patients with allergic rhinitis were selected as the subjects, Randomly divided into two groups,including observed group(n=42) and control group(n=42).The control group was treated with antitussive,expectorant and inhaled corticosteroids, while the observed group in the control group combined with ketotifen 1 mg 2/ day oral treatment,the changes of FeNO and IL-17 in the two groups were compared after one month treament.Result:Before treatment, two groups of patients in general IL-17 and fractional exhaled nitric oxide ware no significant difference(P> 0.05).After treatment, compared to the control group, the observed group was significantly more effective,the difference was statistically significant(P <0.05);fractional exhaled nitric oxide in treatment group were lower than those in control group, the difference was statistically significant(P<0.05,P< 0.01).And the observed group was lower than the control group, and the differences were statistically significant,t(P<0.05).Conclusion:Ketotifen significantly reduce the FeNO of allergic rhinitis and asthma syndrome, reduce airway inflammation. PMID- 29798128 TI - [Modified rhytidectomy incision and modified Blair incision contrast research in superficial parotid gland tumor resection]. AB - Objective:Evaluate the application value of modified rhytidectomy incision in superficial parotid gland tumor resection.Method:Seventy-one patients with tumor in the superficial parotid were included in this study from January 2012 to January 2015. They all accepted superficial parotidectomy or subtotal superficial parotidectomy. Thirty-six cases used modified rhytidectomy incision and 35 cases used modified blair incision. The data of operative field exposure, operating time, bleeding, the rate of complication, score of patients's satisfaction were recorded and compared between the two groups.Result:There was no statistically significant difference between the two groups in the operative field exposure, operating time and bleeding (P > 0.05). No difference was found between the two groups in the rate of facioplegia, while the rate of insensible earlobe in the modified rhytidectomy incision group was significantly lower than the modified blair incision group (P < 0.05). The score of patient's satisfaction in the modified rhytidectomy incision group was significantly higher than the other group (P < 0.05).Conclusion:The modified rhytidectomy incision provides good exposure and has the advantage of less complication and better cosmetic outcome. It is worthy of wide clinical application. PMID- 29798129 TI - [Five cases of the huge sinonasa-pterygopalatine fossaschwannomawere removed by radical maxillary sinusectomy combined with nasalendoscope]. PMID- 29798130 TI - [An analysis of spleen aminopeptide oral lyophilized powder in the treatment of children after tonsillectomy]. PMID- 29798131 TI - [Schwannoma of the ethmoid sinus in children: a case report]. AB - A ten years old male patient,the main symptom was prsented as the left nasal obstruction, repeated hemorrhage with hyposmia. Large translucent neoplasm can be seen in the left side of the nasal cavity. CT and MRI of the nasal sinus showed that the soft tissue density shadow in the left side of the ethmoid sinus and the surrounding bone with no damage. He was treated with nasal endoscopic surgery. Postoperative pathology showed schwannoma. The tumor recurred three years later, and the patient underwent nasal endoscopic surgery again. In the literature we reviewed the case to analyze the reasons of recurrence. PMID- 29798132 TI - [Hypopharyngeal carcinosarcoma: a case report]. AB - Carcinosarcoma is a rare tumor with both malignant epithelium and interstitial components. Tumor entities have been described in many epithelial organs such as the lung, uterus, ovary, prostate and so on. Hypopharyngeal carcinosarcoma is extremely rare. Now we report a case of hypopharyngeal carcinosarcoma in our department in August of 2016 as follows. PMID- 29798133 TI - [Research on the effect of RNA interference on mast cells in respiratory allergic diseases]. AB - Respiratory allergic disease has become a major health problem in the 21st century.Mast cells are key effector cells of the respiratory anaphylaxis, and can form a variety of features of allergic inflammation by producting large numbers of inflammatory mediators.RNAi can affect the disease process by silencing gene expression, and has made significant process in the study of many diseases, but the research of targeting mast cells for the treatment of respiratory allergic diseases is rare.This review focuses on recent advances of the application of RNA interference on mast cell in respiratory allergic diseases, aming to further understand its application in the respiratory allergic diseases and research status, and broaden new ideas of treating respiratory allergies. PMID- 29798135 TI - [The diagnosis and treatment of tinnitus]. PMID- 29798134 TI - [The clinical curative strategies of hypopharyngeal carcinoma]. AB - Hypopharyngeal carcinoma is one of the common tumor of head and neck which is considered to be with doubtful prognosis. The clinical symptoms are not obvious in the early stage because of the anatomical structure. Once patients feel uncomfortable, it would be late for treatment. And most of them are with lymph node metastasis because it's rich of lymphatic system, which makes the treatment more difficult. Comprehensive Treatment which include surgery, radiotherapy and chemotherapy, plays an important role on hypopharyngeal carcinoma. As the progress of clinical medicine and the request on life quality, function preserving treatment is becoming the most important part for the patients. In this paper, we summarize the clinical curative effect of different treatments for hypopharyngeal carcinoma. PMID- 29798136 TI - [Investigation and analysis of tinnitus in diabetic patients]. AB - Objective:To analyze the influencing factors of tinnitus in diabetic patients and the correlation between hearing loss and tinnitus.Method:Participants were patients with diabetes. Subjects were tested for hearing function and tinnitus symptoms by questionnaire and pure tone audiometry.Result:1112 patients (55 were men and 57 were women) were affected by tinnitus symptoms in 255 patients with diabetes,there were no significant differences between the number of male patients and female patients(P=0.278).2The incidence of tinnitus increased with age (<=30 year: 40%, 31-40 year :25%, 41-50 year: 27%, 51-60 year: 43%, >60 year: 55%),and there was significant differences in the number of patients among different age (P=0.001).3The incidence of tinnitus was no significant difference in diabetes patients with different educational level (P=0.648).4Totally 83 subjects who complained hearing impairment were tested for hearing loss by pure tone audiometry, while 113 (66%) of 172 subjects who insisted their hearing were normal had hearing loss. Of the subjects with normal hearing but tinnitus, 72% had hearing loss and 62% of patients without tinnitus actually had hearing loss.5There were statistically significant in patients with diabetes between the incidence of tinnitus and low/intermediate frequency hearing loss or high frequency hearing loss.Conclusion:The incidence of tinnitus symptoms is increased in patients with diabetes mellitus, which may be related to the age, the incidence of hearing loss,however, may be irrelevant to gender and educational level. Diabetic patients with tinnitus symptoms should be tested as soon as possible to achieve early intervention. PMID- 29798137 TI - [Clinical value of psychoacoustic characteristics in patients with idiopathic tinnitus]. AB - Objective:To analyze the relationship between psychological parameters and clinical severity score in patients with idiopathic tinnitus, and clarify the value of psychoacoustic testing in the severity of tinnitus and evaluation of curative effect.Method:A total of 165 patients with idiopathic tinnitus were collected. All patients received conventional audiological and psychoacoustic tests. Psychoacoustic tests include pitch matching (PM), loudness matching(LM), minimal masking levels (MMLs) and residual suppression(RI). Tinnitus handicap inventory (THI) and tinnitus evaluation questionnaire(TEQ) were used to evaluate the severity of tinnitus. SPSS 18.0 was used to analyze the relationship between the severity of tinnitus and psychosocial parameters by univariate analysis and multivariate Logistic regression analysis. Changes of patients psychological parameters were analyzed after five weeks of tinnitustherapy.Result:1Results of univariate analysis showed that there were significant difference with THI score: types of sound and loudness matching sensory level(LMSL) (P<0.05). There were also a significant correlations with TEQ score: the duration of tinnitus, tinnitus pitch matching(PM2) and loudness matching hearing level(LMHL)(P<0.05).2Multivariate analysis showed that PM2 and LMSL had significant correlation with THI(P<0.05), while patients with a single sound were less severe: with the increasing of LMSL, the severity of tinnitus was aggravated. There was also a significant correlation between LMHL and TEQ scores(P<0.05), and the greater the LMHL value, the more severe the tinnitus.3The statistically significant indicators are: LMSL, MMLs, MMLs difference, Feldman curve(P<0.05).Conclusion:The clinical severity of tinnitus is correlated with some psychological parameters of tinnitus. Tinnitus psychoacoustic tests help to assess the clinical severity of tinnitus. PMID- 29798138 TI - [A preliminary study on the correlation between obstructive sleep apnea hypopnea syndrome and chronic tinnitus]. AB - Objective:To investigate and analyze the chronic tinnitus prevalence and its related factors in OSAHS patients.Method:We studied 115 patients who were diagnosed with OSAHS by polysomnography.All patients BMI were calculated. The amount of patients accompanying tinnitus was calculated by investigating the history of tinnitus. Univariate and multivariate logistic analyzes were used to calculate the association between gender, age, hearing loss, BMI, and the lowest SPO2 with tinnitus. The differences in tinnitus prevalence among different age groups and gender were compared using chi-square test.Result:1The prevalence of tinnitus in 115 OSAHS patients was 38.26% (44/115). 2Between the ages of 31-80 years, the prevalence of tinnitus in every 10-year-old group was 9.09%,6.82%,11.36%,38.64%,and 29.55%,respectively.There was a significant difference between the age groups (chi2=14.55,P<0.01). The prevalence of female was 44.12%(15/34) which was higher than the male 35.80%(29/81), there was no significant difference (chi2=0.70,P>0.05). 3The results of univariate and multivariate logistic regression analysis showed that sex, BMI and lowest SPO2 had no correlation with tinnitus in patients with OSAHS, while age and hearing loss were independent correlates of tinnitus(P<0.05).Conclusion:More than 1/3 of patients with OSAHS had chronic tinnitus, both age and hearing loss maybe the risk factors of tinnitus in patients with OSAHS, but neither BMI nor the lowest SPO2 was clearly related to chronic tinnitus. PMID- 29798139 TI - [The investigation rate and influence factors of tinnitus with chronic suppurative otitis media]. AB - Objective:To investigate the incidence of tinnitus and its influencing factors in patients with chronic suppurative otitis media, and to provide clinical data for the study of the pathogenesis of tinnitus.Method:The clinical data of 77 patients with chronic suppurative otitis media who underwent modified radical mastoidectomy and tympanoplasty were investigated. When tinnitus and otitis media happened in the same side,then the tinnitus is judged to be otitis media related. Patients were further divided into otitis media related tinnitus and the no tinnitus groups. The differences of tinnitus severity, sleep disturbance, migraine (migraine features), snoring and gastroesophageal reflux were compared between the two groups in tinnitus occurrence and classification.Result:The incidence of otitis media related tinnitus was 55.8%(43/77). Most of the tinnitus happened(33/43) later than the occurrence of otitis media for several years or even decades. There were 43 cases of tinnitus associated with otitis media, and 31 cases without tinnitus. Between the groups, significant differences were observed in migraine features, and the P value is 0.011, while no significant differences were noticed in the severity of hearing loss and sleep disorders, snoring, gastroesophageal reflux. Ranking of otitis media related tinnitus was positively related to the degree of hearing loss, especially the bone conduction threshold. With Spearman rank correlation test,P values of mean value(250Hz,500Hz,1kHz,2kHz,4kHz), middle frequency (1kHz, 2kHz)and high frequency (4kHz) of bone conduction threshold were 0.010,0.019 and 0.003, and the correlation coefficients were 0.391,0.356 and 0.443, respectively.Conclusion:The occurrence of tinnitus in patients with otitis media may not be consistent with the time of otitis media, and theoretically later than the occurrence of otitis media is more reasonable. Whether tinnitus occurs in patients with otitis media is not related to sleep disorders, the degree of air conduction and bone conduction hearing loss, but is related to migraine features. The severity of tinnitus associated with otitis media is associated with bone conduction hearing loss. PMID- 29798140 TI - [Observation on effect of retraining therapy in patients with chronic tinnitus]. AB - Objective:To analyze the curative effect of tinnitus retraining therapy on patients with chronic decompensated tinnitus and to explore an effective method to treat patients with chronic decompensated tinnitus.Method:Thirty patients were treated for tinnitus retraining therapy for 12 months. The content of retraining therapy includes: tinnitus counseling,low intensity natural sound therapy, shift attention, and relaxation training.Result:The severity of tinnitus was compared in grading before treatment and after 12 months treatment: 56.7%(17/30) of grade III before treatment, 36.7%(11/30) of grade IV and 6.7% (2/30) of grade V;16.7%(5/30) of grade I after treatment, 60.0% (18/30) of grade II,16.7%(5/30) of grade III,6.7% (2/30) of grade IV, where compensatory tinnitu was 76.7%(23/30), and decompensated tinnitus was 23.3%(7/30). The composition ratio of 30 subjects compensated tinnitus and decompensated tinnitus before and after treatment has significant changes, with statistical differences(P<0.01). The mean score of tinnitus severity before treatment was 14.40+/-2.60 in 30 subjects and 9.00+/-2.82 after treatment in assessment scale. There was a significant difference between the both groups(P<0.01).Conclusion:Tinnitus retraining therapy is an effective treatment of chronic decompensated tinnitus. PMID- 29798142 TI - [Influence on compliance of subcutaneous immunotherapy in patients with allergic rhinitis by We-Media management]. AB - Objective:To investigate the influence on compliance of sublingual immunotherapy (SLIT) in patients with allergic rhinitis by We-Media management.Method:One hundred and eighty patients of allergic rhinitis were randomly divided into We Media management group (Group A 90 cases) and telephone management group (Group B 90 cases). All of patients were treated with SLIT. In the group A, the doctor patient WeChat and/or QQ group were formed. The specific duty doctor acted as group leader, made monthly plans, sent SLIT related knowledge more than 3 times a week and assessed patient reported outcomes. In the group B, the patients were conductd on-the-spot demonstration and explanation and followed up by telephone once three month. The statistical analysises were made on the rates and reason of dropouts on the first, third, sixth, ninth, twelfth post-treatment months in two groups.Result:The rates of dropouts in group A and group B were 13.3%(12/90) and 32.2%(29/90) respectively in the first year. The statistical difference were noticeable between group A and group B(P=0.003). Most dropouts were happened in the first 3 months, group A 41.7%(5/12) and group B 51.7%(15/29) respectively. It had no statistically significant(P=0.558). Two major reasons of dropouts were no improvement of symptoms and lack of confidence.Conclusion:Percentage of dropouts in SLIT patients through telephone management was comparatively high, which can be significantly improved by We-Media management. We-Media management has more advantage,especially during long-term follow-up. PMID- 29798143 TI - [An immunohistochemical study of CTHRC1,Vimentin,E-cadherin expression in papillary thyroid carcinoma]. AB - Objective:To investigate the expression and significance of CTHRC1 in patients with papillary thyroid cancinoma.Method:We collected 63 specimens of papillary thyroid carcinoma tissue with 36 specimens of the adjacent normal thyroid tissue and 23 specimens of thyroid nodular goiter. The expressions of CTHRC1 protein in these tissues were detected by immunohistochemical staining. The correlations between the expressions of CTHRC1 with clinicopathologic features,E-cadherin and Vimentin expression were analyzed.Result:CTHRC1 protein expression levels in papillary thyroid carcinoma tissue were significantly higher than those in adjacent normal thyroid tissue and benign disease(P<0.01);CTHRC1 expression was significantly correlated with lymph node metastases(P<0.05). Moreover,CTHRC1 expression was correlated with the expression of E-cadherin and Vimentin(P<0.01).Conclusion:CTHRC1 is related with the occurrence and miligant transformation of papillary thyroid cancinoma. We speculated that CTHRC1 might play a role in the epithelial-mesenchymal transition of papillary thyroid cancinoma. PMID- 29798141 TI - [Relevant factors of tinnitus in the elderly: an analysis of 150 volunteers]. AB - Objective:To evaluate and characterize tinnitus in elderly volunteers,try to find out the relevant factors that can affect the incidence of tinnitus.Method:The study included 150 elderly volunteers. All volunteers had taken the otology examination and pure tone audiometry. They were interviewed by the investigators who were trained together, using the same questionnaire. The characteristics of tinnitus and the relationship between all relevant factors and tinnitus were analyzed.Result:Average age was 71.4 years. There are now 77 patients with tinnitus(51.3%), of which 31 cases have sustained tinnitus for more than 3 months, accounting for 40.3% of existing tinnitus volunteers. There was negative correlation between tinnitus and age. There was positive correlation between tinnitus and hearing loss. Tinnitus and headache had no correlation(P>0.05).Conclusion:After reach a certain age(70 years old), the incidence of tinnitus decreased. Hearing loss might be the most dangerous factor.If the hearing loss was more serious, the incidence of the tinnitus became higher. Tinnitus in the elderly may be the result of a combination of factors. PMID- 29798144 TI - [The exploration of gene promoter methylation profiling in nasal polyp]. AB - Objective:To explore the gene promoter methylation profiles of nasal polyp, and to analysis the promoter methylation differences between the nasal polyp and the normal nasal mucosa.Method:Total DNA of the nasal polyp tissues and normal nasal mucosa were extracted. After immunoprecipitation and whole genome amplification, the DNA was labeled with Cy3/5 and hybridized in NimbleGen hybridization chamber. For array hybridization, Roche Nimblegen CpG Promoter array was used. The slides were scanned using the Axon GenePix 4000B microarray scanner. The different genes were analyzed through pathway and verified by Real-time PCR.Result:3010 genes were found to have promoter hypermethylation in normal nasal mucosa or nasal polyp.2,62%(79/3010) of the genes had promoter hypermethylation in all the nasal polyps, which were negative in normal nasal mucosa.10.66%(321/3010) of the genes had promoter hypermethylation in normal nasal mucosa, which were negative in all the nasal polyps. Three pathways were found in the promoter hypermethylation of the nasal polyps. Fourteen pathways were found in the negative hypermethylation of the nasal polyps.Conclusion:Genes promoter methylation plays an important role in the development of nasal polyps, and the gene promoter methylation profiling may yield new some clues on the mechanism of nasal polyps. PMID- 29798145 TI - [Photochemical induced vestibular ischemia?with icy water test in guinea pigs]. AB - Objective:To ascertain the effects of a new method of photochemical reaction in vestibular function in guinea pigs.Method:Local photochemical reaction was initiated by systemic injection of rose bengal(20mg), photoillumination of the vestibule through medial wall of epitympanum for 30 minutes was started immediately after the injection of rose bengal, with a optic fiber connected to a xenon light (wavelength, 540nm; photointense, 500-600 mW/cm 2). There were 20 guinea pigs divided random equally into 2 groups. Group 1 was injected with rose bengal. Group 2 was control, injected with physiological saline solution. The ice caloric tests were performed on the second day.Result:The test group (7 ears) and the control group (6 ears) with test nystagmus showed mean frequencies were(2.0+/ 0.33)times/s and(3.7+/-0.33)times/s,the mean amplitude were (3.1+/-0.39)mm and (3.5+/-0.54)mm,and the mean duration were (44.7+/-17.22)s and (62.0+/-7.22)s respectively.The nystagmus frequency difference was statistically significant, but the amplitude and the duration of the nystagmus were not significantly different. There was no obvious spontaneous nystagmus in the two groups, and there were negative results of ice water test (3 ears in the test group and 4 ears in the control group).Conclusion:Photochemical reaction can induce the ischemic state of the vestibule system in guinea pig, and produce an acute vestibular dysfunction, and ice water test shows that the frequency of nystagmus is reduced. PMID- 29798146 TI - [Risk factors of papillary thyroid carcinoma in different ages of young patients]. AB - Objective:To investigate the clinical characteristics of the risk factors of papillary thyroid carcinoma in different ages of young patients (<45y)associated with carbon nanoparticles.Method:A retrospective statistics and analysis of 183 patients who were diagnosed and treated; carbon nanoparticles were injected into the thyroid during operation and at last the conventional pathological diagnosis were papillary thyroid carcinoma of all patients; to analysis the gender, tumor size, capsular invasion, lymph node metastasis, multifocality and other risk factors between the <25y and 25-<5y patients.Result:The parathyroid were better identified, while the central lymph nodes better turned black after carbon nanoparticles injected; <25y compared to 25-<45y in the tumor size, multifocality, capsular invasion, extrathyroidal extension, associated with Hashimoto Thyroiditis, the differences had statistical significant(P<0.01 or P<0.05).In young (<45y) thyroid papillary carcinoma, preoperative serum thyroglobulin level was beyond the normal range, indicating a large possibility of lateral neck lymph node metastasized, but the two age groups had no statistical significant(P>0.05) in serum thyroglobulin and thyroid stimulating hormone.Conclusion:Carbon nanoparticles can effectively recognize parathyroid and trace central lymph nodes. In the <25y groups, the tumor diameter is more likely to exceed 1cm, the lateral neck nodes are more easily metastasized, capsular invasion and extrathyroidal extension are also more easily to turn up. While the 25-<45y groups are more likely to form multifocality, which may be accompanied by Hashimoto Thyroiditis and prone to occur central lymph nodes metastasized. In the younger patients (<45y), the more preoperative serum thyroglobulin higher, the more probable lateral neck nodes metastasized. PMID- 29798147 TI - [The analysis of the curative effect of low-temperature plasma cauterization on the treatment of 146 cases of congenital pyriform sinus fistula]. AB - Objective:To investigate the therapeutic effect of low-temperature plasma cauterization on the treatment of congenital pyriform sinus fistula(CPSF).Method:All the 146 patients with CPSF received imaging examination, and the low-temperature plasma cauterization under laryngoscope was performed in the stage of inflammation control.Result:After 6-59 months of follow-up, all patients did not have pharynx fistula, and no massive hemorrhage occurred during and after operation. Nine cases of hoarseness after operation 2 d-1 months to restore normal. Thirty cases were suspected of recurrence, of which 8 cases were cured after incision and drainage, and 4 cases were cured after two cauterization.Conclusion:Low-temperature plasma cauterization is the preferred treatment for the microinvasive, simple, beautiful and repeatable operation of PSF, which can be sugessted as the first-line choice for the treatment of sinus and fistula. PMID- 29798148 TI - [Efficacy of endoscopic approach to reconstruct the medial orbital fracture with perpendicular plate of ethmoid]. AB - Objective:To study the efficacy of endoscopic sinus approach in the repair of medial orbital fracture with perpendicular plate of ethmoid.Method:Retrospective chart was reviewed in 10 cases receiving endoscopic approach to reconstruct the medial orbital fracture with perpendicular plate of ethmoid.We observed the improvement of the symptom such as diplopia, eye movement,and enophthalmos of the preoperative and postoperative.Result:After postoperative follow-up of 4 months to 23 months, all the patients had no graft loss or displacement, infection and other complications, and except for 1 patient with mild diplopia, other patients recovered completely, including eye movement disorder, diplopia,and enophthalmos.Conclusion:Endoscopic approach is a safe and effective treatment in the repair of medial orbital fracture with perpendicular plate of ethmoid. PMID- 29798149 TI - [The protective effect of optimized target delineation in intensity modulated radiation therapy on swallowing function in patients with different TNM staging of nasopharyngeal carcinoma]. AB - Objective:To investigate the protective effect of optimized target delineation in intensity modulated radiation therapy(IMRT) on swallowing function in patients with different TNM staging of nasopharyngeal carcinoma.Method:Fifty patients with nasopharyngeal carcinoma were enrolled in this study. They were randomly divided into 25 cases of experimental group and 25 cases of control group by random number table and received IMRT treatment. Patients in control group only received routine delineation of target areas, the patients in experimental group were given the delineation of the relevant parts of the swallowing on the basis of the control group.And then, the degree of dysphagia, xerostomia, weight loss, and quality of life were assessed in the two groups of patients during and after IMRT.Result:There was no significant change in the degree of dysphagia in stage II patients during radiotherapy, but the degree of dysphagia in stage III and IV patients increased with the increase of radiotherapy time. After the end of radiotherapy, there was no significant change in the degree of dysphagia in the control group of patients. Compared with the 0th week after the end of radiotherapy, the stage II patients in experimental group showed significant improvement in week 12(P<0.05), while the stage III and IV patients showed significant improvement in week 24 after radiotherapy(P<0.05). The degree of xerostomia of two groups of patients continued to increase with varying degrees during and after IMRT(P<0.05 or P<0.01). The weight of the two groups of patients during radiotherapy continued to decrease with the increase of radiotherapy time,and gradually recovered after the end of radiotherapy.And in the experimental group, the weight loss was significantly lower in week 12 and week 24 than in the control group (P<0.05). During radiotherapy, the quality of life scores of the two groups became lower and lower with the increase of radiotherapy time compared with the 0th week of radiotherapy. After the end of radiotherapy, the quality of life began to gradually improve, and in week 24 after the end of radiotherapy, the quality of life of the experimental group of patients was significantly higher than that of the control group (P<0.05).Conclusion:During radiotherapy of patients with nasopharyngeal carcinoma, the structural organs associated with swallowing function are given individualized target delineation can reduce the occurring of dysphagia due to radiotherapy and improve the quality of life of patients after radiotherapy. PMID- 29798150 TI - [Curative effect observation of methylprednisolone combined with continuous negative pressure drainage in the treatment of pseudocyst of auricle]. PMID- 29798151 TI - [Nasopharyngeal tuberculosis: report 2 cases and review of the literature]. AB - Nasopharyngeal tuberculosis is a noteworthy disease and it should be differentiated from with nasopharyngeal carcinoma,especially in southern China,because of both having similar clinical presentations such as cervical lymph node enlargement and lesions in nasopharynx. Here we report 2 middle-aged patients of nasopharyngeal tuberculosis;between them,one was male, another was female. They came to hospital with the symptoms of pharyngeal pain and neck node, respectively. The former patient was accompanied by repeated fever. His chest radiographic displayed suspected active lesions; and nasopharyngeal examination inspected irregular mucosa with white patch covering the nasopharyngeal area; and magnetic resonance imaging (MRI) presented diffuse thickening of the mucosal wall of nasopharynx; moreover, the biopsy specimen pathological results showed ulceration with mucosal squamous papillary hyperplasia.Finally,acid-fast staining of nasopharyngeal secretions disclosed acid-fast bacilli was positive. However, the latter patient was completely different from the former in clinical presentations, while MRI finding was almost the same. In addition, the endoscopy depicted that characteristic of nasopharyngeal lesion was smooth, congested and swelling, and the pathological result revealed granulomatous inflammation with epithelioid histiocytes and multinucleated giant cells of Langerhans type.Combined their clinical manifestations with various laboratory and imaging examinations, both of the two patients were eventually diagnosed as nasopharyngeal tuberculosis. PMID- 29798152 TI - [Frontal tuberous xanthomas with xanthelasma: one case report]. AB - : The male patient of 51 years old was admitted due to find forehead tumor for 8 years. Auxiliary examination: platelet 80*108/L, heterosexual platelet morphology examination showed microscopic see platelet scattered more easily to large and giant platelet-based, part of the platelet particles to reduce. High-density lipoprotein:0.93mmol/L, totalbilirubin:20.55MUmol/L, directbilirubin:5.47MUmol/L, alanine aminotransferase:70.16MUmol/L,aspartate aminotrans-ferase:93.26 MUmol/L. Head computed tomography(CT) showed department of subcutaneous soft tissue shadow, clear boundaries,uniform density,no obvious adjacent bone destruction. DIAGNOSIS: 1Forehead tumor. 2Juvenile platelet syndrom.3Spleen resection.4Liver dysfunction. Forehead tumor resection under general anesthesia was applied to the patient.Pathological examination prompted:(frontal) tuberous xanthoma. Postoperative recovery is good and follow-up at present. PMID- 29798153 TI - [The treatment progress of myofunctional therapy for obstructive sleep apnea hypopnea syndrome]. AB - OSAHS, as a kind of sleep-related breathing disorder,is harm to the health. Myofunctional therapy firstly originated in the speech function training. As a kind of noninvasive treatment, myofunctional therapy is effective in OSAHS and can be used as an effective way of adjuvant therapy. In order to make it being drawn attention, the origin,method of myofunctional therapy and its curative effect and mechanism of OSAHS were reviewed in this paper. PMID- 29798154 TI - [The research progress of ceRNA in the head and neck carcinoma]. AB - Competitive endogenous RNA(ceRNA) refers to the regulatory model that RNAs can regulate each other expression by competing for common miRNA response elements at post-transcriptional levels. The ceRNA network links the function of protein coding genes(mRNAs) with the functions of non-coding RNAs (such as miRNAs, long non-coding RNAs, pseudogenes transcripts,and circular RNAs) and plays an important role in the development of multiple tumors. The head and neck carcinoma is a highly aggressive malignant tumor. Although the treatment methods continue to improve,the survival rate of head and neck carcinoma patients has no more significant improvement. It is particularly important to explore the molecular mechanisms of the development and metastasis of head and neck carcinoma,look for specific molecular diagnostic markers and therapeutic targets.We summarize the role of ceRNA regulatory networks in the development of head and neck carcinoma in the present review. PMID- 29798155 TI - [Research progress in imaging of large vestibular aqueduct syndrome]. AB - Large vestibular aqueduct syndrome is one of the common non-syndromic hearing impairment. It is one of the most common inner ear abnormalities that cause hearing loss in children.The main performance is gradual or fluctuant hearing loss, from basic normal to extremely severe. Frequently seen in high frequencies hearing loss. The air-bone conduction gaps present in pure tone audiometry test with low frequencies. There were some inducements of intracranial pressure increases before premorbid. Some patients could be accompanied by vertigo or instability. So far, there was still no effective way to terminate the patient deafness progress.If there was no effective intervention,the speech developmental delay of children were an inevitable trend,greatly affect their normal social communication learning ability. So, early diagnosis was critical. Imaging examination was the golden criterion for the diagnosis of LAVS.Characteristic audiological performance and gene diagnosis can be the basis of the further diagnosed. Because the structure and anatomical location of vestibular aqueduct is small and deep, normal imaging examination is difficult to display its morphology and structure,so,for a long time, it did not work very well. Until the advent of High-resolution computed tomography and magnetic resonance imaging, there was a breakthrough and a deeper understanding of the fine structure with inner ear. We reviewed the latest progress of large vestibular aqueduct syndrome imaging studies. PMID- 29798157 TI - [Treatment of high-risk and complicate foreign bodies in respiratory tract]. AB - Objective:To explore the treatment of the high-risk and complicate foreign bodies in respiratory tract. Method:Retrospective analysis of 3 330 cases of respiratory foreign bodies were performed, from 2003 January to 2016 November, including 205 cases of high-risk and complicate cases, foreign bodies including plastic caps, plastic or glass lamp beads, animal bones, metal objects, and foreign bodies such as peanuts. Result:In one hundred and seventy-five cases, foreign bodies were taken out directly by hard bronchoscope, in twenty-eight cases, foreign bodies were removed by fiberoptic bronchoscope, one case of foreign body was removed with thoracotomy and one case of foreign body died. Conclusion::To treat high risk foreign bodies in respiratory tract, sufficient preoperative preparation or rapid response are both important, including selecting the appropriate equipment, surgery and anesthesia, in order to successfully remove the foreign body and minimize complications. PMID- 29798156 TI - [The role of CTLA-4 in the pathogenesis of chronic tonsillitis]. AB - Objective:The purposes of the present study were to explore the role of CTLA-4 in the pathogenesis on development of chronic tonsillitis, and to provide new possibilities and theoretical basis for the drug therapy of chronic tonsillitis and, from soft regulation of the inflammatory immune response point of view. Method:Tonsil tissues were obtained by tonsillectomy and classified into two groups according to clinical forms of tonsillitis, CT (chronic tonsillitis) group (n=21) and TH (hypertrophy of tonsil) group (n=15). We used HE staining to observe the pathological changes in the structure of tonsil tissue in different groups. We used immunofluorescence (IF) method to determine the differences in expression of CTLA-4 between two groups and their distribution characteristics , and used Real-time fluorescent quantitative PCR technique (qRT-PCR) to detect CTLA-4 mRNA expression in the two groups. Result:1HE staining showed the pathogeny structure mainly characterized as the follicular hyperplasia and germinal center in CT group, and obvious "star" phenomenons in TH group. 2Immunofluorescence results showed that the average fluorescence intensity and density of CTLA-4 protein in CT group was significantly higher than in TH group (P<0.05), the difference was statistically significant. 3The qRT-PCR experiment results showed that the expression level of CTLA-4 mRNA in CT group were obviously higher than in HT group (t=6.294, P<0.01), and the differences were statistically significant too. Conclusion:We found CTLA-4 played an important role in the development of chronic tonsillitis disease, suggesting that the mechanism of immunosuppression may exist in the process of chronic tonsil inflammation. Tonsil lymphoid tissue immune suppression provided a new explanation for recurrent tonsillitis, and provides a possibility for the development of new drugs for the treatment of chronic tonsillitis with the exception of surgery recurrent tonsillitis, at the same time for the clinical treatment of chronic tonsillitis in addition to surgery, but the possibility of researching new drugs from the perspective of immunology. PMID- 29798158 TI - [Vestibular function tests for vestibular migraine: clinical implication of video head impulse and caloric tests]. AB - Objective:To review the results of caloric test and the video head impulse test (vHIT) in a cohort of VM patients and assessed the value of each for predicting the prognosis in VM patients. Method:A retrospective analysis was performed on VM patients in our vertigo clinic, vestibular function were assessed by caloric test and vHIT at the initial visit and 6 months after treatment. Complete response (CR) was defined as no need for continued medication, uncomplete response (UR) as improved symptoms but need for continued medication, no symptomatic improvement. Result:At the initial evaluation, 15 of 75 (15.0%) exhibited abnormal caloric test results, 9 of 75 patients (12.0%) exhibited abnormal vHIT results. Six months later, 58 of 75 patients (77.3%) no longer required medication (CR), while 17 (22.7%)UR patients need for continued medication. The ratio of abnormal vHIT gain and abnormal caloric results were significantly different between group (CR) and group (UR) (P<0.05). Conclusion:Abnormal vHIT and caloric test results revealed semicircular canal dysfunction in VM patients, peripheral vestibular abnormalities are closely related to the development of vertigo in VM patients and predicted prolonged preventive medication and vestibular rehabilitation requirement. PMID- 29798159 TI - [The analysis of the electrode impedance in different periods after cochlear implantation performed with round window insertion in steroid deposition]. AB - Objective:To study the variation of the electrode impedance in different periods after cochlear implantation performed with round window insertion in steroid deposition, and to provide the basis for the postoperative debugging of the speech processor. Method:Detected the electrode impedance of 47 cochlear receivers after operation in steroid deposition from September 2014 to October 2015, compared the impedance values between different periods, and different groups according to their locations. Result:The average impedance of all the electrodes and the 3 subgroups are low after implantation (period A0), peaked at the first month (period A1), then decreased slowly, and then turned to be stable at the sixth month (period A3); the impedance values were no significantly different between the sixth month (period A3) and the twelfth month (period A4) while were significantly different between each of other two periods (P<0.05); the apical group had the highest impedance and the basal group had the lowest impedance in all the 5 periods. Conclusion:The local use of steroid can decrease the impedance of the electrode after implantation. The impedance value were the low during operation, peaked at the first month, then decreased slowly, and turned to be stable at the sixth month. As a result, the cochlear implant should be debugged at regular intervals in 6 months after operation to obtain the best hearing status. PMID- 29798160 TI - [Correlation between TLR4 gene polymorphisms and allergic rhinitis]. AB - Objective:To investigate the correlation between polymorphisms in the TLR4 locus and the susceptibility of allergic rhinitis. Method:Three polymorphisms in TLR4 locus (rs10759930, rs2737190 and rs2770150) were genotyped in 212 subjects with allergic rhinitis and in 169 healthy controls. PCR sequencing methods was performed for genotyping. SPSS program version 17.0 was used for statistic analysis. The characteristic of genetic polymorphism was analyzed. The differences of genotype and allele frequencies between the two groups of children were compared. Result:Heterozygous mutations CT (P=2.70*10-6, OR=2.66, 95%CI=1.76 4.00), and homozygous mutation TT (P=9.72*10-9, OR=8.78, 95%CI=3.83-20.13) of rs10759930 appeared significant, are related to AR. Conclusion:Heterozygous and homozygous allele in rs10759930 is associated with allergic rhinitis. PMID- 29798161 TI - [Functional modified periauricular incision in parotidectomya]. AB - Objective:The purpose of this study was to present the usefulness of modified periauricular incision in parotid surgical procedures. Method:Sixteen consecutive partial superfacial parotidectomies were performed using modified periauricular incision. Clinical evaluation of cosmetic satisfaction, incidence of complications such as Frey's syndrome, facial nerve palsy, earlobe numbness and salivary fistula were observed. Result:The parotid tumors were removed in all cases with need for any further skin procedures, as the incisions produced a good aesthetic result. The average scale of cosmetic satisfaction are 9.2. Temporary paralysis of the facial nerve were found in two patients, and six patients felt numbness around earlobe after operation. Hey all recovered in 1 to 3 months after surgery. All patient healed without salivary fistula and Frey's syndrome. No recurrence was happened during follow-up in 6 to 30 months (median follow-up period was 22 months). Conclusion:The results of the present study indicate that modified periauricular incision have a high-quality and highly aesthetic option for surgical procedures concerning benign conditions of the parotid gland. PMID- 29798162 TI - [Phonological assessment and voice analysis of thyroid surgery patients]. AB - Objective:To investigate the changes of speech and voice acoustics in patients with thyroid disease before and after operation, get objective values, and conducive to guiding the clinical diagnosis and treatment and recurrent laryngeal nerve protection. Method:A total of 216 patients undergoing thyroid surgery from October 2015 to October 2016 were treated with TVQ and GRBAS at 1 day before surgery, 1 week, 1 month, and 3 months postoperatively to phonological assessment, and Praat software was used to collect and analyze the acoustic acoustics index for preoperative and postoperative comparative analysis. Result:All patients did not damage the recurrent laryngeal nerve, unilateral or bilateral thyroid subtotal resection (no exploration of recurrent laryngeal nerve) in patients with postoperative speech and voice index F0 was decreased at 1 week after surgery (P<0.05), the other indicators did not change significantly; difference was found out in single-sided total thyroidectomy+ipsilateral central area lymph node dissection, bilateral thyroidectomy+unilateral central area lymph node dissection (exploration of unilateral recurrent laryngeal nerve) in patients with TVQ, GRBAS and F0, HNR after surgery 1 week compared with preoperative (P<0.05), However, there was no significant difference 3 months; TVQ, GRBAS and F0, HNR were significantly changed in patients with bilateral thyroidectomy+bilateral central lymph node dissection (revealed bilateral recurrent laryngeal nerve) at 1 week after operation (P>0.05). F0 and HNR were lower than those before operation, and the patients were treated with Jitter and Shimmer. The patients were treated with TVQ, GRBAS, Jitter and Shimmer before operation, however, the majority of patients' TVQ, GRBAS, Jitter, Shimmer can be restored to preoperative level after surgery 3 months (P>0.05). Conclusion:The appearance of speech and voice problems in patients after thyroid surgery may increase with the expansion of the surgical range, the change in speech and voice after neck lymph node dissection is reversible. PMID- 29798163 TI - [Application of voice acoustic analysis of surgical effect in children with benign hyperplastic vocal cord disease]. AB - Objective:To evaluate the use of voice acoustic analysis in children with hyperplasia diseases of vocal cords. Method:The software developed by Dr.Speech was used to do acoustic analysis for 93 children patients with vocal cords hyperplasia diseases before the operation, 15 and 30 days after the operation, and 76 normal subjects were also analyzed as the controls. Result:The Jitter, Shimmer and NNE parameters were higher, and HNR, SNR parameters were significant lower in vocal cords hyperplasia diseases group than in normal controls (P<0.01). The Jitter, Shimmer and NNE decreased, HNR, SNR increased 15 days and 30 days after the operation in vocal cords hyperplasia diseases group. Compared with preoperative group, there was a highly statistically significant at 15 and 30 days after the operation (P<0.01). All the data returned to normal levels 30 days after surgery. Conclusion:Voice acoustic analysis can evaluate the quality of children voice and the surgical effect objectively and quantitatively. PMID- 29798164 TI - [A comparative study of therapy effects between esomeprazole plus mosapride citrate and botulinum toxin injection on vocal process granuloma]. AB - Objective:Anti-reflux medications or botulinum toxin A injections are the main current therapies for the definite vocal process granuloma. This studies is focusing on comparing the effects of proton pump inhibitors plus prokinetic agents with botulinum toxin A injections on vocal process granuloma. Method:Adult patients in our outpatient department (from December 2014 to June 2016) complaining of trachyphonia and/or abnormal pharyngeal sensations who were found to have contact granulomas (38 cases) were included. Patients were divided into two groups according to the treatment selected by themselves: esomeprazole with mosapride citrate (n=28) or botulinum toxin A injection (n=20). The reflux symptom index and reflux finding score determined by electronic fibrolaryngoscopy were utilized to assess efficacy. Result:There was no statistical difference on age, sex and reflux symptom index and reflux finding score before treatment between the two groups. Total effective rate in the esomeprazole with mosapride citrate group and the botulinum toxin A group were 96.43% and 45.00%, separately. The recorded symptoms after therapy resolved with a statistically significant improvement in the esomeprazole with mosapride citrate group. Conclusion:Combined proton pump inhibitor plus prokinetic drug therapy plays a significant role in the treatment of vocal process granulomas. PMID- 29798165 TI - [Preliminary study on the expression of CD4+CD25+Tregs and Foxp3 in peripheral blood of patients with head and neck squamous cell carcinoma]. AB - Objective:This paper discusses the expression and significance of CD4+CD25+ Tregs and Foxp3 in peripheral blood of patients with head and neck squamous cell carcinoma. Method:We have collected 40 cases of head and neck squamous cell carcinoma patients with newly diagnosed or relapse after treatment, all of them underwent surgery, 39 males and 1 females, aged 41-79 years, in our department from January 2014 to December 2015. At the same time, 10 healthy volunteers are enrolled as control group. 2 ml peripheral blood has been detected by flow cytometry, and the ratio of CD4+CD25+/CD4+ and CD4+CD25+Fxop3+/CD4+ are calculated, respectively. SPSS 23.0 is used for statistical analysis. Result:CD4+CD25+ Tregs is highly expressed in head and neck tumors, compared with that in the healthy control, and the difference is statistically significant (P<0.01). There is significant difference between the early and late stage (P<0.05). The positive rate of Foxp3+ is higher in CD4+CD25+ Tregs positive cells than in control group (P<0.01). The difference of positive rate between late stage and early stage head and neck tumors is statistically significant (P<0.05). There is a significant positive correlation between CD4+CD25+ Tregs and Foxp3 (r=0.95). Conclusion:CD4+CD25+ Tregs and Foxp3 are highly expressed in the peripheral blood of patients with head and neck squamous cell carcinoma. Through the inhibition of the immune system in patients with head and neck squamous cell carcinoma, the development of carcinoma were promoted. PMID- 29798166 TI - [Clinical treatment of metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites]. AB - Objective:To discuss the diagnosis, treatment and prognosis of metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites. Method:The clinical data of 5 patients involved papillary thyroid carcinoma with cervical lymph nodal metastasis with occult primary sites from 2009 to 2015 were analyzed. Result:According to preoperation examinations, two of them only underwent neck lymph node resection and three patients underwent asubtotal or total thyroidectomy plus neck lymph node dissection. All the pathological results showed that there were metastatic papillary thyroid carcinoma in cervical lymph nodal, but the primary sites of thyroid tissue were normal. After 1 to 7 year follow-up, there was no recurrence. Conclusion:Whether to take the thyroidectomy need to be carefully considered thyroidectomy in patients with metastatic papillary thyroid carcinoma in cervical lymph nodal with occult primary sites. PMID- 29798167 TI - [Relationship between obstructive sleep apnea syndrome and cognitive impairment and functional status after stroke]. AB - Objective:To analyze the correlation between obstructive sleep apnea syndrome (OSAHS) and cognitive impairment and functional status after stroke. Method:From February 2014 to September 2016, a total of 189 patients were included in the study, 33 patients with mild OSAHS were excluded, and finally 86 patients in the study group and 70 patients in the control group were included in the final analysis. The main indicators included the cognitive and functional status. Cognitive status was assessed by nine dimensions: vigilance, attention, memory, working memory, executive, language, insight, mental activity, psychomotor, and intelligence. Functional status was assessed using neurological status and functional independence. Secondary measures included sleepiness, fatigue, anxiety and depression, and sleep quality. Result:The age of the study group was higher than the control group, the BMI was higher than the control group, the average hospitalization time was longer than the control group, and all of the difference were statistically significant (all P<0.05). The total cognitive status of the two groups was significantly different, and the total cognitive status study group was significantly worse than in the control group (t=9.276, P=0.012). In the nine dimensions of cognitive ability, the study group's attention, execution, insight, mental adjustment and intelligence were lower than the control group, and the difference was statistically significant (P<0.05). The functional status of the study group was worse than that of the control group (t=38.094, P=0.000). There were no significant differences between the two groups in terms of sleepiness, fatigue, sleep quality, anxiety and depression (P>0.05). Conclusion:The cognitive impairment and functional status of stroke patients with OSAHS are significantly worse. OSAHS is a risk factor for poor prognosis in stroke patients. PMID- 29798168 TI - [Differences in myringoplasty between endoscopic and microscope]. AB - Objective:The intraoperative and postoperative clinical indexes of myringoplasty performed by endoscope or by microscope were collected retrospectively, the differences between the two different surgical methods were analysized. Method:Retrospective analysis of the clinical data of 70 cases (70 ears) udergoing myringoplasty in the department of Otolaryngology-Head and Neck Surgery, at the Second People's Hospital of Kashi from June 2014 to August 2015. According to the surgical approach cases were divided into two groups, 30 cases in group A by endoscopic myringoplasty and 40 cases in group B by microscope myringoplasty. The operation time, blood loss, postoperative dry ear time, wound healing scar hyperplasia, tympanic membrane perforation rate and hearing improvement rate were compared between the two groups, and SPSS 19.0 statistical software was used to analyze the differences between the two groups. Result:The operation time: Group A had an average of (35.23+/-6.38)min, less than group B (42.60+/-7.97)min, with statistical difference (P<0.05). The intraoperative blood loss: the average of group A was (7.33+/-2.11)ml, less than group B (17.93+/ 3.84)ml, with statistical difference (P<0.05). The postoperative dry ear time more than 1 month: group A was 40%, lower than Group B (75%), with statistical difference (P<0.05). The postoperative incision healing scar hyperplasia: group A was 0%, lower than group B (5%), no significant difference (P>0.05). The tympanic membrane perforation rate: group A was 3.33%, lower than group B (7.5%), no significant difference (P>0.05). The postoperative hearing improvement rate: group A was 76.67%, lower than group B (80.00%), no significant difference (P>0.05). Conclusion:Compared with the traditional microscope surgery, endoscopic myringoplasty is a minimally invasive surgical technique which can get the same curative effect, but with a shorter operation time, less intraoperative blood loss, dry ear in shorter time , recovery more quickly, beautiful incision and other advantages. So it is worthy of clinical application. PMID- 29798169 TI - [Study of minimally invasive treatment of low-temperative plasma for the congenital pyriform sinus fistula during acute infection phase]. PMID- 29798170 TI - [The aging changes of the nasal septum in adolescents]. PMID- 29798171 TI - [Therapeutic effect of two kinds of surgical treatment for chronic dacryocystitis: external dacryocystorhinostomy and endoscopic dacryocystorhinostomy]. PMID- 29798172 TI - [Nasal catheter drainage for treatment of retropharyngeal abscess]. PMID- 29798173 TI - [Inflammatory myofibroblastic tumor: a case report]. AB - A 59 years old woman with chief complain of intermittent hemoptysis and shortness of breath was admitted to our hospital. Fiberoptic laryngoscope: no abnormality seen; enhanced computerized tomography of the neck showed that at the second trachea ring located a round nodule with a diameter of about 23 mm, flat on the sixth cervical vertebrae, consider vascular tumors. The immunohistochemistry: an inflammatory myofibroblastic tumor. PMID- 29798174 TI - [Complete endoscopic resection of septonasal chondrosarcoma by coblation: two cases report]. AB - Septonasal chondrosarcoma is extremely rare, though chondrosarcoma ranks the third in bone malignant tumors. Typical symptoms can be lack duing to elusive anatomical structure of the nasal sinuses, which easily leads to misdiagnosis. Here we reported two cases of low-grade chondrosarcoma deriving from nasal septom removed by intranasal endoscope using coblation. MRI and CT scan revealed typical ring-and-arc appearance. Treatment with septonasal chondrosarcoma varied from neoplasm staging and surgical approcaches had been reported long disease-free survival. PMID- 29798175 TI - [Triple semicircular canal occlusion with cochlear implantation for delayed endolymphatic hydrops: a case report]. AB - A 46-year-old female with profound sensorineural hearing loss in her left ear from childhood developed tinnitus and fluctuating hearing loss on the right side 8 years ago. Four years later, paroxysmal episodes of rotatory vertigo occurred with gradually increased frequency, lasting from half an hour to 2 hours and accompanied with nausea and vomiting. Audiometric test revealed severe sensorineural hearing loss in both of her ears. The tympanograms showed type A on both sides. The threshold of auditory brainstem response was 97 dBnHL in her right ear while no waves could be educed on her left side. Weakened right-sided vestibular function was confirmed on caloric testing and vestibular-evoked myogenic potential. A normal cochlear morphology and clearness cerebellopontine angle were shown in the MR imaging scan. She was diagnosed with Delayed Endolymphatic Hydrops. PMID- 29798176 TI - [External nose eccrine poroma:a case report]. AB - Eccrine poroma is a benign neoplasm of the terminal duct. It is commonly located in distal extremities but rarely present in head and neck. This report mainly describes a case of external nose eccrine poroma. We will clarify the disease from pathology; histopathological examination; diagnosis; clinical manifestations to prognosis. PMID- 29798177 TI - [Research progress of intervention strategies on voice disorders in children with vocal nodules]. AB - Vocal nodules in children is one of the common diseases in children, characterized as the hoarse voice of the children, which is mainly due to improper use of sound long-term or excessive use of the voice. The hoarseness of children's voice undermine not only the physical and mental health of children, but also the quality of life of children and their families. In recent years, the incidence of vocal nodules in children has been increasing. There are considerable differences between the children's own characteristics and adults such as bronchial lumen and cognitive and cooperate aspects, which lead to a large number of difficulties for clinical diagnosis and intervention. Based on a large number of literatures, this paper reviews the risk factors, diagnosis, voice assessment and intervention strategies of vocal nodules in children, in order to provide more comprehensive reference for the medical workers. PMID- 29798178 TI - [The regulatory mechanisms of 1,25(OH)2D3 in allergic rhinitis]. AB - Nearly 30 years at home and abroad, the study found that Vitamin D can adjust congenital and acquired immune at the same time. As a result, Vitamin D is expected to be used for prevention and treatment of allergic rhinitis. But about vitamin D supplement to the mechanism of action of allergic disease such as allergic rhinitis is still not clear, there is no consistent condusion, even some of the result also has certain contradiction, so vitamin D is not routinely used for clinical therapy. This review will help us to understand the mechanism of action of vitamin D for allergic rhinitis in the treatment of thinking in the future. PMID- 29798179 TI - [Immunotherapies for head and neck squamous cell carcinomas]. AB - The Head and neck squamous cell carcinoma (HNSCC) is a group of heterogeneous diseases. Patients with HNSCC demonstrate poor prognosis and survival time with standard therapy, especially in patients with advanced HNSCC. Recurrence and metastasis have not yet been effectively controlled. The immune profile in HNSCC, whether caused by carcinogen exposure or human papillomavirus (HPV), showed significantly immunosuppression. With the understanding of the complex interaction between tumor and immune system and immune escape mechanism of HNSCC, new immunotherapies have been generating. This article will summarize the immunological mechanism and immune therapy of HNSCC currently.?. PMID- 29798180 TI - [Clinical observation of coblation assisted transoral microsurgery for the treatment of oral and oropharygneal malignancy]. AB - Objective:To evaluate the feasibility and effectiveness of coblation assisted transoral surgery for the treatment of oral and oropharyngeal malignancy. Method:19 patients who suffered from oral or oropharyngeal malignant tumors underwent coblation assisted transoral surgery from August 2008 to August 2017 were studied. According to the tumor sites and pathological results, there were four oral squamous cell carcinoma (SCC) (two tongue carcinoma and two mouth floor carcinoma), eleven oropharygneal SCC (five tonsillar carcinoma, four soft palate carcinoma, one tongue base cartinama and one multiple carcinoma invading both soft palatine and hypopharynx), and four lymphatic and hematopoietic malignancies (three tonsillar tumors and one tumor invading both tonsil and tongue base). According to AJCC guideline, the stages of four oral SCC were T1N0M0, T1N2M0, T2N1M0, and T2N2M0 respectively; while the stages of eleven orophygneal SCC were T1N0M0 for 5 patients, T2N0M0 for 4 patients, T2N1M0 for one patient, and T2N2M0 for one patient respectively. Result:Among the 19 patients studied, concurrent neck dissections and tracheotomies were performed in six and four patients respectively. For all the transoral procedures, the blood loss could be controlled within 20 ml, while the operative time were controlled within two hours. 13 patients started oral feeding the day they were operated on. All of the four patients who underwent the tracheotomy could be decannulated successfully after surgery. Four patients diagnosed as lymphatic and hematopoietic malignancies turned to hematology department for further treatments. For the remaining 15 SCC patients, 14 were followed up successfully with one loss to follow-up: the follow up time ranged from 6 to 108 months, during these times, one patient with multiple carcinomas invading the soft palate and hypopharynx had developed new carcinomas located in contralateral hypopharynx and esophagus and had the metastasis in cervical lymph nodes 5 months after surgery, another patient with soft palate carcinoma had the metastasis in cervical lymph nodes 18 months after surgery. Two patients died because of intracranial hemorrhage and cardiovascular event 5 and 12 months after surgery respectively. The three years' tumor free survival and overall survival rates calculated by Kaplan-Meier method were 75.0% and 77.9% respectively. All patients had no severe dysfunctions for swallow, speech and breathing related to the surgery. Conclusion:Radiofrenquency coblation assisted transoral surgery for oral and oropharygneal carcinoma has definite therapeutic effect. Most cases can avoid open surgery and tracheotomy.The advantages are blood control, simplifing surgery,shortening operational time,faster recovery, lower incidence of complications and better preservation of organ function. PMID- 29798181 TI - [Coblation and silicon stent implantation for recurrent laryngeal papilloma with extensive lesions]. AB - Objective:To evaluate the feasibility and long-term outcome of radiofrequency coblation combined with silicon stent implantation in the treatment of recurrent laryngeal papilloma with extensive lesions. Method:From March 2009 to April 2016, a total of 13 patients (8 males, 5 females; aged 28-67 years) who suffered recurrent laryngeal papilloma were enrolled in this retrospective study. All the cases had undergone at least one operation at other hospitals before this hospitalization. The recurrence interval (RI) of these cases ranged from 2 to 6 months. Video-laryngoscopy or stroboscopy were preformed preoperatively and postoperatively, as well as vocal function assessment. These cases underwent radiofrequency coblationin combination of different stent implantation (member, 7 cases; tube, 4 cases; T-shaped tube, 2 cases) under general anesthesia. The follow-up was 12 to 76 months. Result:Laryngoscopy revealed that the lesions mainly located in the vocal folds, anterior commissure, ventricular band, posterior commissure, epiglottis and even in subglottic area. Varying extent of mucosal adhesion of anterior or/and posterior commissure were observed in all cases, and two cases suffered mild subglottic tracheal stenosis. Two to six weeks after surgery, the silicon stent were removed and no mucosal adhesion were found except for 2 cases who suffered mucosal adhesion of anterior commissure again. Compared to preoperative scores, VHI-10 and G scores showed the significant improvement of voice quality postoperatively in all cases. The recurrence of papilloma was observed in 3 cases during 1-year follow-up, and 4 cases during 2 year follow-up, no recurrence in 6 cases. These recurrence lesions mainly located in ventricular band, subglottic area and trachea. However, no recurrence occurred in these cases who received ablation again. No serious complications were observed in these cases. Conclusion:Radiofrequency ablation may be an effective approach in the treatment of recurrent laryngeal papilloma with extensive lesions. One-stage application of suitable silicon stents can effectively prevent the adhesion of the wound and the onset oflaryngo-tracheal stenosis, and improve the quality of voice. PMID- 29798182 TI - [Treatment of children's pharyngeal stenosis following pharyngeal surgery with coblation]. AB - Objective:Pharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) with coblation is rare and may be difficult to treat. This report is to explore the causes of pharyngeal stenosis and presents our successful treatment experience. Method:From Jan 2012 to July 2016, 5 children with pharyngeal stenosis (2 nasopharyngeal stenosis and 3 nasopharyngeal stenosis combined with oropharyngeal stenosis) secondary to pharyngeal surgery (tonsillectomy/adenoidectomy) in Peking Union Medical College Hospital were analyzed. Five cases with severe nasopharyngeal stenosis received surgery of scar resection, horizontal-to-vertical pharyngoplasty and local pharyngeal flap rotation; and three of them received free skin transplantation. After stenosis repair surgery, prolonged nasopharyngeal hollow stents were used for more than 6 months. To evaluate the therapeutic effect, pharyngeal cavities and symptoms of difficulty nasal breathing, mouth breathing, difficulty in blowing nose, hyponasal speech, snoring, restless sleep, anosmia, dysphagia were assessed and compared before and after surgery. Result:With 7-46 months follow up, all symptoms of the 5 cases are ameliorated and the diameters of nasopharyx are more than 1.5 cm. No velopharyngeal insufficiency complication happened. Conclusion:Improper operation with coblation can cause severe pharyngeal stenosis. Flap rotation, horizontal-to-vertical pharyngoplasty and prolonged use nasopharyngeal hollow stents are reliable methods to correct pharyngeal stenosis following children's pharyngeal surgery. PMID- 29798183 TI - [Complications analysis of adenoidectomy and tonsillectomy assisted with ablation on children]. AB - Objective:To analyze the complications of adenotonsilectomy assisted with coblation in children. Method:Complications of 2 089 cases of children with adenoid and tonsil surgery assisted with coblation, in our hospital nearly 10 years, were analyzed by epidemiological methods through the method of retrospective analysis. Result:1the sex ratio of male to female was 2.08:1, average age (5.87+/-3.12) years old, and most of 2 089 cases 76.35% (1 595/2 089) were 3-7 years old; 2all cases underwent adenoidectomy. Different surgery methods of tonsil consisted of three groups as partial resection associated with ablation was 69.17% (1 445/2 089), ablation (channeling) alone was 22.26% (465/2 089) and total resection was 8.57% (179/208). The amount of bleeding in operation was (8.52+/-3.18)ml, average operation time was (30.15+/-8.26) minutes, the postoperative pain score was (3.77+/-1.61); 3The incidence of postoperative complications: postoperative bleeding (all were secondary bleeding cases) rate was 0.24% (5/2 089), recurrence rate was 0.14% (3/2 089), prevertebral lymphadenitis was 0.96% (20/2 089), the other was 0.29% (torus hyperplasia in 2 cases, dyspnea in 2 cases, 1 cases of angle of mouth burned, nasopharyngeal adhesion in 1 cases). Postoperative fever rate was 9.81% (205/2 089). Conclusion:coblation technique is a good method for the treatment of children's adenoids and tonsil diseases with high efficiency and low complications. But improving the operation procedure proficiency level and skills of operation is an important link to reduce complications. PMID- 29798184 TI - [Sternohyoid myocutaneous flap in pediatric laryngotracheal stenosis treatment]. AB - Objective:To assess the indications and outcomes of laryngotracheal reconstruction (LTR) using the sternohyoid myocutaneous flap (SMF) in pediatric patients with laryngotracheal stenosis. Method:Twenty patients (15 males, 5 females; mean age, 9 years old, range 3 to 14) with laryngotracheal stenosis who underwent SMF procedures at Tangdu Hospital between August 1991 and October 2014 were analyzed. Stenosis was classified according to the Myer-Cotton grading system. Four patients were grade II, ten were grade III, and six were grade IV. The mean length of stenosis was 1.8 cm (rang, 0.3-4.0 cm). Three patients had concomitant unilateral vocal paralysis and 2 had bilateral vocal paralysis. Result:Fourteen of 20 patients (70%) were decannulated. The prevalence of decannulation for grade II, III, and IV was 100%, 70%, and 50%, respectively. There were no severe complications. Conclusion:The SMF is a relatively simple and reliable method for LTR but should be used cautiously if employed in severe cases such as grade IV with long-segment stenosis. PMID- 29798185 TI - [Differences in clinical features of post-traumatic olfactory dysfunction and non post-traumatic olfactory dysfunction: a follow-up study]. AB - Objective:To analyze the clinical features and recovery rate of post-traumatic olfactory dysfunction (PTOD) in Chinese adults in a case control follow-up study. Method:The clinical data of 202 patients who were diagnosed with olfactory dysfunction between January 2015 and December 2016 and followed up for 14 to 473 days were analyzed in this retrospective study. The patients were divided into those with PTODs (PTOD group) and those without PTODs (non-PTOD group). The two groups were compared with regard to age (years), sex, olfactory function (Sniffin' sticks), gustatory function (triple drop method), chemosensory evoked potentials, and magnetic resonance imaging (MRI) characteristics of olfactory pathways. The recovery rate of PTOD was evaluated by Sniffin' sticks and triple drop method. Result:Patients in the PTOD group (40+/-11 years) were significantly younger than those in the non-PTOD group (47+/-15 years), whereas the number of men and women was similar in both groups. The mean TDI score (Sniffin' sticks) was significantly different between the PTOD (12+/-5) and non-PTOD (19+/-8) groups (P<0.05). The mean oERP P2 latency was significantly shorter for the non PTOD group (418+/-64 ms) than for the PTOD group (483+/-82 ms, P<0.05). There were no significant differences in the mean oERP N1 latency, N1 amplitude, P2 amplitude, mean tERP P2 latency and MRI between the two groups. After the follow up period, 8.9% (5/56) and 5.4% (3/56) patients in the PTOD group exhibited an improvement in olfactory function and gustatory function, respectively. Conclusion:PTOD should be considered a type of disability that can lead to serious accidents, and an adequate understanding of its clinical features and etiologies is critical for appropriate diagnosis and treatment and for improving the prognosis of treatment. The rate of recovery of olfactory function is higher than that of gustatory function in patients with PTOD; further investigations are required in this regard. PMID- 29798186 TI - [Evaluation of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in children of obstructive sleep apnea hypopnea syndrome]. AB - Objective:To evaluate neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in children of obstructive sleep apnea hypopnea syndrome (OSAHS). Method:122 cases of OSAHS patients were selected, and divided into 3 groups: mild OSAHS group (41 cases), moderate OSAHS group (41 cases), and severe OSAHS group (40 cases), according to the stage apnea hypoventilation index (AHI) and the lowest oxygen saturation (LSaO2). In addition, 40 cases healthy children were selected as control group. The differences NLR and PLR between 4 groups were compared. Result:The NLR in the severe OSAHS group (1.57+/-0.58) was significantly higher than that in the normal control group (0.98+/-0.22), mild OSAHS group (1.24+/-0.47), and moderate OSAHS group (1.36+/-0.46), P<0.05. However, there was no significant difference in PLR between the normal control group and other OSAHS groups (P> 0.05). A positive correlation between AHI and NLR (r=0.385,P=0.000), and a negative correlation between AHI and minimal oxygen saturation were observed (r=-0.686,P=0.000). Conclusion:NLR might be used as a marker to evaluate the severity of inflammatory status in OSAHS patients, but PLR could no. PMID- 29798188 TI - [The clinical features and prognosis analysis of adenoid cystic carcinoma in nasal cavity and paranasal sinus]. AB - Objective:To investigate the clinical features and prognosis of adenoid cystic carcinoma (ACC) in nasal cavity and sinus. Method:67 patients with ACC were recruited interview in our department from 2007 to 2017. The association between clinical parameters and survival were evaluated by statistical analysis. Result:The 1-, 5- and 10- overall survival were 95%, 79%, 67%, and the 1-, 3- and 5-year recurrence rate were 5%, 7%, 9%, respectively. Simple factor analysis displays that age, the location of the tumour, clinical stages, sex, the interval time between starting symptoms to diagnosis time, the expression quantity of Ki 67 were related to the prognosis, and the latter three and surgical margin were also influential factors of distant metastasis after treatment. Multi-factors analysis revealed that sex, the interval time between starting symptoms to diagnosis time, the expression quantity of Ki-67 were significant factors for prognosis, and the latter two and surgical margin were influential factors of distant metastasis after treatment. Conclusion:The sex and the interval time between starting symptoms to diagnosis time and Ki-67 may be independent prognostic factors for ACC. The interval time between starting symptoms to diagnosis time and Ki-67 level may be independent factors of distant metastasis after treatment. Patients with long interval time between starting symptoms to diagnosis time and high expression of Ki-67 may have a higher risk of recurrence and mortality, which need reexamination of cycle-time reduction. The surgical margin is influential factor of distant metastasis, but not for the patients' prognosis. PMID- 29798187 TI - [Anxiety and depression in patients with sudden sensorineural hearing loss and its influencing factors]. AB - Objective:To evaluate the psychological status of anxiety and depression in patients with sudden sensorineural hearing loss, and to analyze the factors that affect the occurrence of anxiety and depression. Method:A total of 198 patients with moderate and severe sudden sensorineural hearing loss were enrolled. The patients were tested by general condition questionnaire and hospital anxiety and depression scale (HADS). Patients who developed anxiety and depression were tested again using the HADS at 1 week after completion of the treatment. Result:The incidence of anxiety was 27.27% in patients with moderate and severe sudden sensorineural hearing loss, and the incidence of depression was 25.25%. The scores of anxiety and depression were statistically significant (P<0.05). The multivariate logistic regression analysis showed that the status of anxiety and depression was accompanied by symptoms and other diseases (P<0.05). There was a significant difference between the effective group, the significant efficacy group and the cured group (P<0.05). The difference between the scores before and after treatment was compared. Differences in the ineffective group compared with the other three groups, and the cured group compared with the other three groups of anxiety, depression were statistically significant. Conclusion:The problem of anxiety and depression in patients with moderate and severe sudden sensorineural hearing loss is relatively prominent, and the symptoms of anxiety and depression are obviously affected by the symptoms and other diseases. After treatment, anxiety and depression status changes significantly. In clinical practice, anxiety and depression and its influencing factors should be taken into account for the treatment of the patients with severe sudden sensorineural hearing loss. PMID- 29798189 TI - [Application of dysphonia severity index in laryngeal reflux related voice diseases]. AB - Objective:To discuss the validity and reliability of dysphonia severity index in evaluating the effect of diagnosis and treatment of laryngeal reflux related voice diseases. Method:54 cases of voice disease patients accompanied by laryngopharyngeal reflux from January 2016 to June 2017 in department of otorhinolaryngology of our hospital were divided into two groups according to treatment type. 32 cases in the operation group received laser surgery and standard acid suppression therapy for 6 weeks, and 22 patients in the non operation group received standard acid suppression therapy for 6 weeks. 24 h multichannel impedance pH (MCII-pH) monitoring was carried out. The indexes of reflux symptom, reflux finding score, subjective auditory perception and objective acoustic parameters of voice were measured before and after treatment, and the dysphonia severity index was calculated and analyzed. Result:There was no significant difference in age, sex and course of disease between the two groups (P> 0.05).?Compared with pre-treatment, RSI, RFS, Jitter, Shimmer, G and R in two groups decreased significantly after treatment, and MPT, DSI increased significantly (P<0.05). Before treatment, RSI, RFS, Jitter, Shimmer, G and R in the operation group were significantly higher than those in the non-operation group, and MPT, DSI were lower (P<0.05). There were no significant differences in the parameters between the two groups after treatment (P> 0.05). DSI was negatively correlated with GRBAS scoring parameters, Jitter and Shimmer, and positively correlated with RSI, RFS, and MPT (P<0.01). DSI is related to the location of the lesion (P<0.05) The incidence of anxiety was 27.27% in patients with moderate and severe sudden sensorineural hearing loss, and the incidence of depression was 25.25%. The scores of anxiety and depression were statistically significant (P<0.05). The multivariate logistic regression analysis showed that the status of anxiety and depression was accompanied by symptoms and other diseases (P<0.05). There was a significant difference between the effective group, the significant efficacy group and the cured group (P<0.05). The difference between the scores before and after treatment was compared. Differences in the ineffective group compared with the other three groups, and the cured group compared with the other three groups of anxiety, depression were statistically significant. Conclusion:DSI can be used as an objective evaluation index for the diagnosis and treatment of laryngeal reflux related voice diseases, and it is accurate and reliable. PMID- 29798190 TI - [The expression of IL-22 in nasal polyps tissues]. AB - Objective:To analyze the expression of IL-22 in nasal polyps and the expression of Th22 cells. Method:The concentrations of IL-22 in nasal polyps were determined by ELISA. The mononuclear cells infiltrated in nasal polyps were separated and flow cytometry was used to analyze the expression of IL-22 in CD4+ T cells and the counts of Th22 cells. Result:Compared with the control group, the expression of IL-22 in nasal polyps did not change significantly, however the expression of IL-22 in CD4+ T cells increased. Furthermore the number of Th22 cells in the tissue increased significantly. Conclusion:The expression of Th22 cells in nasal polyps is significantly increased, which may play an important role in local chronic inflammatory mucosal immunity. PMID- 29798191 TI - [Expand pedicle forehead flap in the repair of whole nasal defect]. AB - Objective:To observed the application of expanded pedicle forehead flap in nasal defect. Method:Totally 11 whole nasal defect cases in our department from June 2010 to March 2016 were treated with the expanded pedicle forehead flap. Regular follow-up was performed after operation to observe the survival condition of flaps, shape, color, texture and scar in donor site after nasal repair. Result:The expanded pedicle forehead flap and transplantation of autologous costal cartilage nasal stents were all survived, the reconstruction nasal shape was satisfied. After 1-5 years follow up, the repair using expanded forehead flap had a good color with enough blood supply, and the nasal ventilation function is well. There was only one linear scar leaved in donor site. Conclusion:Application of the expanded pedicle forehead flap is a good mothed for the treatment of whole nasal defect. PMID- 29798193 TI - [The experience on diagnosis and treatment of the third branchial anormal]. PMID- 29798192 TI - [Effect of APP on prognosis in patients with chronic rhinosinusitis after endoscopic sinus surgery]. AB - Objective:To investigate interventional effect of APP on prognosis in patients with chronic rhinosinusitis after endoscopic sinus surgery. Method:One hundred and forty-four chronic rhinosinusitis patients in our hospital were divided into observation group and control group randomly; observation group had 71 patients, and control group had 73 patients. The control group was treated with standard discharge instruction. In addition to standard discharge instruction, observation group was followed up and directed by using of APP. Two groups' VAS scores and Lund-Kennedy scores were compared in admission time, and 6 months after discharge. Result:There was no significant difference in the Lund-Kennedy scores and VAS scores between the two groups in admission time. However, 6 months after discharge, Lund-Kennedy scores and VAS scores in observation group were obviously lower than control group?(P< 0.05). Conclusion:The use of healthy APP can significantly promote patients with chronic rhinosinusitis recovery and re-visit after endoscopic sinus surgery. PMID- 29798194 TI - [Practice experience of laternal neck incision in the operation of parapharyngeal spece neoplasms]. PMID- 29798195 TI - [The clinical analysis of solitary lateral neck node metastasis in 10 cases of thyroid carcinoma]. PMID- 29798196 TI - [The clinical research of arytenoid dislocation]. PMID- 29798197 TI - [Recent advances in early diagnosis of head and neck cancer in precision medicine era]. AB - Head and neck squamous cell carcinoma, HNSCC, has high morbidity and mortality. Even in America, more than 1/2 to 2/3 patients have been diagnosed at advanced stage. So, it's urgent to find ways to diagnose HNSCC earlier and foresee the curative effect. With the achievement of Next-Generation Sequencing, researchers are trying to develop early diagnostic technology from a new perspective, such as personal genomics, proteomics, metabolomics and other related personal information. Here we reviewed the recent research in early diagnosis of HNSCC. PMID- 29798198 TI - [Systematic review on orofacial myofunctional therapy to treat obstructive sleep apnea-hypopnea syndrome]. AB - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an important risk factor for cardiovascular and cerebrovascular diseases. The widespread collapse of the airway, which can't maintain its normal position and structure, is an important cause of OSAHS. Noninvasive ventilator-assisted ventilation is the preferred treatment for OSAHS, but there are shortcomings of poor compliance. Orofacial myofunctional therapy (OMT) is a noninvasive, simple, low-cost, low-risk therapy that is expected to replace noninvasive ventilator-assisted ventilation to a certain extent. So far, there is little Chinese literature on OMT, especially no training methods in Chinese version. Therefore, this paper systematically reviewed anatomical abnormalities and pathology of OSAHS, possible treatment mechanism of OMT and related research progress. And we translated two kinds of training method of OMT (Guimarase's and Hemmat Baz's) into Chinese for researchers and clinicians' reference, which is widely cited in foreign literature. PMID- 29798199 TI - [Research advances of pregnancy rhinitis]. AB - Rhinitis during pregnancy refers to the various causes of rhinitis during the pregnancy, such as allergic rhinitis, vasomotor rhinitis, drug rhinitis, etc. Patients could have symptom before pregnancy, during pregnancy or postpartum symptoms. Pregnancy rhinitis (PR) appear only in pregnancy, and the main clinical manifestations is nasal congestion and the symptom disappeared after pregnancy. There are some similarities between PR and rhinitis during pregnancy, but the clinical feature, treatment option and prognosis are different. PR can affect the quality of life throughout pregnancy, and may even lead to increased risk of OSAHS in women and a threat to maternal and baby's safety. This article will review the research progress of the pregnancy rhinitis. PMID- 29798200 TI - [Exploration of transoral robotic surgery in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome]. AB - Transoral robotic surgery (TORS) is a relatively new technique in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome, which has been shown to be safe and feasible. TORS provides a minimally invasive, visualization method, which brings an unprecedented breakthrough in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome. In this paper, the application and development prospect of TORS in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome will be reviewed. PMID- 29798201 TI - [A multicenter randomized controlled study on the treatment of acute and chronic pharyngitis with Binglianqingye Spray]. AB - Objective:To further evaluate the clinical efficacy and safety of Binglianqingye Spray on acute and chronic pharyngitis by clinical observation. Method:A randomized, double-blind and multicenter clinical trial which served Jinsangzi Tablet and Jinhoujian Spray as the control groups was conducted to observe the effect of Binglianqingye Spray on 360 patients with acute and chronic pharyngitis. Result:Binglianqingye Spray could significantly improve the symptoms with the exact clinical efficacy of the acute pharyngitis or chronic pharyngitis, such as sore throat, pharyngeal mucosa and uvula, dry throat burning, headache, cough, pharynx posterior wall lymphoid follicles hyperemia swelling and mandibular angle lymph node swelling and so on, but it occasionally occurred urine abnormalities and urine sugar adverse reactions. At the same time, the taste satisfaction was 82.1%. Conclusion:The combined effects of Binglianqingye Spray on the treatment of acute pharyngitis or chronic pharyngitis are well, the adverse reaction is rare and the patient's compliance is high. PMID- 29798202 TI - [The effects of PM 2.5 and air quality index on the emergency of otolaryngology]. AB - Objective:To discuss the effects of PM 2.5 and air quality index on the emergency of otolaryngology. Method:Collect in 2015 Beijing tongren hospital emergency department patients with acute otitis media, epistaxis, acute epiglottitis as well as the same time Beijing AQI value and the PM 2.5 density data as the experimental group 1, chooses in 2015 first Affiliated Hospital of Hebei North University similar patient as well as the same time Zhangjiakou AQI value and the PM 2.5 density as the experimental group 2. Statistics the quantity of each sickness of two groups, and the relationships with PM 2.5 and AQI value; Group all data by AQI value and statistics the differences in the incidence rates of each group. Result:The number of cases of acute otitis media and epistaxis in the 2 experimental group were all correlated with the change of PM 2.5 and AQI value, and the correlation was positive between the two groups, However, the incidence of acute epiglottitis was not significantly correlated with the concentration of PM 2.5 and AQI, and there was no significant correlation between the two. The air quality when severe and more pollution when the number of the cases of acute otitis media and epistaxis compared with good air quality for the number of P<0.05, the difference was statistically significant. Conclusion:The increase of PM 2.5 concentration and AQI index is a health risk factor for acute otitis media and epistaxis. PMID- 29798203 TI - [Differential evaluation of diagnostic criteria for pediatric obstructive sleep apnea hypopnea syndrome]. AB - Objective:To evaluate the difference of accessing pediatric sleep symptoms and living qualities between 3 diagnostic criteria: American Thoracic Society (ATS), International Classification of Sleep Disorder (ICSD-3), domestic Urumqi criterion (Draft); To investigate the relationship of PSG parameters and quality of life scale OSA-18. Method:Children with snoring who received PSG in Capital Medical University Beijing Tongren Hospital were recruited from Jan 2016 to Apr 2017. Subjects were diagnosed and grouped to SS, ICSD, ATS&ICSD (ATS&ICSD1, ATS&ICSD2) according to 3 criteria: ATS (AHI>5 or OAI>1), ICSD-3 (OAHI>=1) and Urumqi (AHI>5 or OAI>1, with LSaO2<92%). Subjects' height, weight as well as quality of life scale OSA-18 were recorded. Result:Five hundred and fifteen children were finally included (Male: 350 cases, Female: 165 cases). There were 315, 70 and 130 children in group SS, ICSD, ATS&ICSD respectively. Weights and BMI of ICSD and ATS&ICSD were significantly higher than those of SS (P<0.05), and dysplasia scale of ATS&ICSD was higher than SS (P<0.05); after adjusting height, weight and BMI, sub-scores of sleep disorder were statistically different between 3 groups (P<0.05). Numbers and indexes of respiratory events other than central apneas and hypopneas in group SS, ICSD and ATS&ICSD were increased sequentially and statistically different (P<0.05); numbers and indexes of respiratory events other than mixed apneas in ATS&ICSD2 were significantly higher than that of ATS&ICSD1 (P<0.05). Conclusion:OAHI>=1/h combined with LSaO2<92% should be used as pediatric OSAHS diagnostic criterion. PMID- 29798204 TI - [Expression of long non-coding RNA LINC00460 in laryngeal squamous cell carcinoma tissue and its clinical significance]. AB - Objective:To understand the expression of LINC00460 in laryngeal squamous cell carcinoma (LSCC), and to discuss the role of LINC00460 in carcinogenesis and development of laryngeal squamous cell carcinoma. Method:The expression of LINC00460 in 68 laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues were examined by real-time PCR. The relationship between the expression levels of LINC00460 and the clinicopathological features including clinical stage, histological grade, pathological type, and lymph node metastasis in LSCC was analyzed according to the clinical data. Result:The expression of LINC00460 was significantly upregulated in the LSCC tissue compared with that of adjacent normal mucosal tissue (P=0.006). There were no statistical differences of the quantity of LINC00460 expression among supraglottic, glottic and subglottic LSCC (P>0.05). Moreover, LINC00460 had no significant changes in poorly differentiated LSCC when compared with that of well and moderately differentiated LSCC (P>0.05). Furthermore, the expression of LINC00460 in LSCC with lymph node metastasis had no significant changes when compared with that without of lymph node metastasis (P>0.05). Notably, LINC00460 expression in T1+T2 stages patients were significantly lower than T3+T4 stages (P<0.05). Conclusiont:Upregulation of long non-coding RNA LINC00460 might contribute to the carcinogenesis and development of LSCC, furthermore play important biological function. PMID- 29798205 TI - [The technique of retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction treating middle ear cholesteatoma]. AB - Objective:To investigate the surgical treatment of cholesteatoma of the middle ear. Method:A retrospective analysis of patients from June 2013 to July 2016 diagnosed as cholesteatoma. 137 ears were divided into A group (retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction for 75 ears) and B group (canal wall down mastoidotympanoplasty for 62 ears). the extent and damage of cholesteatoma were observed, comparing the time of dry ear and epithelial postoperative, the incidence of complications such as dizziness and hearing changes. Result:compared with B group, the postoperative dry ear time, epithelial time and hearing improvement in the A group were obviously improved, and the incidence of vertigo after operation was decreased, and the anatomical and physiological functions of the external auditory canal were protected. Conclusiont:The technique of retaining part of the external auditory canal posterior wall with epitympanoplasty in soft wall reconstruction is conductive to the removal of lesions and normal anatomical and physiological protection to external auditory canal, can prevent the forming of the abstraction pocket effectively and the recurrence of cholesteatoma, has clinical and practical value. PMID- 29798206 TI - [Effects of double-dose antihistamine or combined therapy in allergic rhinitis]. AB - Objective:To compare the efficacy and side effects of combined therapy with single-dose oral antihistamine and intranasal corticosteroid to monotherapy with double-dose oral antihistamine in the treatment of seasonal allergic rhinitis. Method:Eighty-two patients with seasonal allergic rhinitis caused by cypress pollen were enrolled in a randomized, parallel-group studycomparing 2 weeks therapy of either 10mg oral ebastine plus 200 MUg intranasal mometasone furoate once daily (combined group) or 20 mg oral ebastine once daily (double-dose group) during the pollen season. Daily rhinoconjunctivitis symptom score and rescue medication use were recorded in both groups. After the treatment period, questionnaires were used to survey the side effects of medicines and dosage form preference of the patients. The levels of IL-6, IL-8 and TNF-alpha in the peripheral blood were measured before and after the therapy. Result:During the cypress pollen season, the daily rhinoconjunctivitis symptom score of the combined group (n=42, 3.7+/-0.4) was significantly lower than that of double-dose group (n=40, 4.5+/-0.5), P<0.001. The daily rescue medication score of the combined group (1.3+/-0.6) was also significantly lower than double-dose group(1.7+/-0.7), P<0.001. The daily medication cost of combined group was 7.08+/ 0.33 Yuan, which was less than that of double-dose group (7.28+/-0.51 Yuan, P=0.002). There was no statistical difference in the rate of adverse reactions between the two groups. The peripheral levels of IL-6, IL-8 and TNF-alpha in two groups did not show significant difference at the end of therapy . Conclusion:The combined therapy with single-dose oral antihistamine and intranasal corticosteroid was superior to the monotherapy with double-dose oral antihistamine in the treatment of seasonal allergic rhinitis in our study. PMID- 29798207 TI - [Efficacy of nasal spray-type allergen blocker combined with oral antihistamines in patients with dust mite allergic AR]. AB - Objective:To investigate the clinical effect of nasal spray type allergen blocker combined with oral antihistamine on dust mite allergic allergic rhinitis (AR). Method:Ninety cases of patients withmild-severe allergic to dust mite were randomly divided into experimental group and control group, 45 cases in each group. The experimental group used nasal spray allergen barrier agent combined with citrate tablets, and the control group used physiological seawater combined with citrate sheet. The symptoms of subjective rhinitis, objective signs, improvement of quality of life scores and adverse reactionsof 2 groups were evaluated before and 2 weeks after treatment. Result:The symptoms, signs and quality of life of the patients in the experimental group were better than those in the control group (P<0.05). No obvious adverse reactions were observed. Conclusion:The effect of nasal spray type allergen blocker combined with antihistamine on AR patients with allergic to dust mite is remarkable. They can significantly alleviate the symptoms and signs of rhinitis in patients, and is worthy to be popularized in clinical application. PMID- 29798208 TI - [Minimum battery of test inhalant allergens needed in screening?allergic rhinitis patients in Beijing]. AB - Objective:The aim was to assess the prevalence of sensitized inhalant allergens in patients with allergic rhinitis (AR), analyze the differences of aeroallergen sensitization rates (SRs) in different areas, and define the minimal number and the type of aeroallergens required to identify patients as sensitized. Method:Six thousand two hundred and eighty five patients suffering from AR symptoms in Beijing, Heilongjiang, Inner Mongolia, Hebei and Shandong areas underwent standardized skin prick test (SPT) with 20 common aeroallergens during the period from Jan 2011 to Jul 2013 when seeking medical help in Beijing Tongren Hospital. The differences of aeroallergen sensitization rates in different areas were compared. Chi square was used in statistical analysis. Conditional approach allowed to determine the aeroallergen selection. Result:Among the 6 285 self reported AR patients investigated, 5 575 (88.7%) patients had at least one positive skin prick reaction. The most common aeroallergen in Beijing, Heilongjiang, Hebei and Shandongwere house dust mites (HDMs). SRs of HDMs in these four areas decreased with latitude increment, whereas SRs of mugwort, ragweed and dandelion in these four areas increased with latitude increment. The three most prevalent aeroallergens in Inner Mongolia were mugwort (59.86%), ragweed (47.62%) and dandelion (46.26%), respectively. Overall, 8 allergens allowed identification >=95% of sensitized subjects in Beijing. Conclusion:Der f was the most prevalent allergen in patients with AR in Beijing, Heilongjiang, Hebei and Shandong Areas, whereas SR of mugwort was highest in Inner Mongolia. Sensitization pattern of aeroallergens varied with areas. Eight allergens allowed identification of the majority of sensitized subjects in screening panels for allergy in Beijing. PMID- 29798209 TI - [The long-term benefits of cochlear implantation for children and their families]. AB - Objective:To study the auditory language ability of children with artificial cochlea after entering normal schools as well as the school life conditions and to evaluate the long-term comprehensive benefits of surgery on children along with their families. Method:The questionnaire was designed referring to the categories of auditory performance (CAP), the speech intelligibility rating (SIR), and family burden scale of diseases (FBS), with the questions involving four aspects of the general conditions, the auditory language ability, the school life conditions and the family conditions. Altogether 50 families were participated. Children who had applied artificial cochlea for at least two years and studied in normal schools were selected as the studying objects. The follow up questionnaire was conducted on the parents. The differences were compared in the auditory language ability and the school life conditions, grouped by gender, age at surgery, parents' educational level, residence, service time of artificial cochlea and parent-child time in general. Meanwhile, the differences of 15 family conditions were compared before and after surgery. Result:The variable factors were of no obvious statistical significance in the comparison among groups of the auditory language ability (P>0.05); In the comparison of the school life conditions, there were significant differences in the number of making friends when grouped by parent-child time (P<0.05), there wes no statistical significance in the comparison among groups of the remaining various factors (P>0.05); In the comparison of family conditions before and after surgery, the rest of the indexes were of significant differences (P<0.05), there was no significant differences in the economic burden and social time of parents (P>0.05). Family conditions improved evidently after surgery. Conclusiont:Under the circumstances of different variable factors, after 2 years of rehabilitation, children are able to acquire better auditory language ability, and adjust themselves to the school life, finishing their studies, still there is a deficiency in the aspect of organizational competence in comparison to age-matched children. In addition, with children's recovery and attending schools, parents' mental stress is significantly reduced, family life returns to normal, and family atmosphere becomes harmonious. Not only can the artificial cochlea help rid children of disability, but also it can be of obvious benefits to their families. PMID- 29798210 TI - [The study of association of chronic rhinosinusitis inflammation subtype with bronchial inflammation phenotype]. AB - Objective:We sought to compare clinical characteristics between eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma, and explored the association of chronic rhinosinusitis inflammation subtypewith bronchial inflammation phenotype in CRSwNP with asthma. Method:Fifty-one consecutive patients suffering from CRSwNP with asthma undergoing endoscopic sinus surgery (ESS) were recruited. Preoperative computed tomography (CT), skin prick test, bronchial provocation test, lung function, and oral fractional exhaled nitric oxide (FeNO) measurements were conducted. Venous blood was taken within 1 week before ESS. Nasal polyps (NPs) specimens were obtained from each patient during ESS, and stained with hematoxylin and eosin. According to the pathologic characteristics of NP samples, fifty-one patients suffering from CRSwNP with asthma were grouped as eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP and three levels of eosinophil infiltration were recognized. Result:Fifty-one patients suffering from CRSwNP with asthma were grouped as ECRSwNP (n=33) and non ECRSwNP (n=18). History of surgery, history of allergy, Lund-Mackay scores, duration of asthma, frequency of severity asthma, numbers of asthma exacerbation in the last year, FeNO, blood eosinophil percentage and absolute count were all significantly higher in the ECRSwNP with asthma group compared with the non ECRSwNP with asthma group (P<0.05). Blood eosinophil percentage had a significant correlation with degree of eosinophil infiltration in NPs (r=0.459, P<0.01) and FeNO (r=0.591, P<0.01). There was a correlation between degree of eosinophil infiltration in NPs and FeNO (r=0.556, P<0.01). Furthermore, Lund-Mackay scores had a positive correlation with blood eosinophil percentage (r=0.327, P<0.05) and degree of eosinophil infiltration in NPs (r=0.412, P<0.01) and FeNO (r=0.691, P<0.01). Conclusion:There is different clinical characteristics between ECRSwNP with asthma and non-ECRSwNP with asthma. These data suggest that CRSwNP inflammation subtype is significantly correlated with bronchial inflammation phenotype in patients suffering from CRSwNP with asthma. PMID- 29798212 TI - [Application and reliability verification of Beijing-based cognitive assessment scale of montreal in cognitive function of adult OSAHS]. AB - Objective:To evaluate the cognitive function of adult OSAHS patients by MoCA-BJ, and to evaluate the reliability and efficacy of MoCA-BJ. Method:A study was conducted on the cognitive function of 94 patients with mild, moderate and severe OSAHS and 28 healthy controls using the MoCA-BJ and the simple mental state examination scale (MMSE). After 14 days, 10 subjects in the healthy control group were tested for MoCA-BJ again. The internal consistency of MoCA-BJ and the Pearson correlation coefficient were used to test the retest reliability. In addition, the simultaneous validity of MoCA-BJ was assessed by comparison with MMSE. Result:The MoCA-BJ internal consistency of the Kronbach coefficient alpha was reliable (0.810). The Pearson correlation coefficient test was highly reproducible (r=0.898, P<0.001). The overall score of MoCA-BJ in the control group was significantly higher than that in the OSAHS group (P<0.01). In the visual spatial ability, the performance of severe OSAHS group was significantly weaker than that of the control group (P<0.01) and non-severe patients (P<0.01). In the executive ability, the control group was significantly higher than the OSAHS group (P<0.05), and the performance of patients with severe OSAHS was weaker than that of non-severe group (P<0.01) and control group (P<0.05), but there was no difference among every group in the trail making test. Attention, the difference between the control group and the patients was significant (P<0.01), but no difference between severe patients and non-severe patients. The total score of the language,the difference between the control group and the patient group was significant (P<0.01), while there was no difference between severe and non-severe patients. The study also found that the results of language repetition, delayed recall and the total score of the language was exactly the same. Orientation,there was also significant difference between the control group and the severe group (P<0.05). There was also significant difference between the severe and non-severe patients (P<0.05). The optimal cutoff between the control and patient groups was 25.5 points (total MoCA score). In addition, in the visual spatial subscale, the cutoff between non-severe and severe OSAHS groups was 2.5 points. The correlation between MoCA score and MMSE score was statistically significant (r=0.764, P<0.01). Conclusion:In summary, our study shows that MoCA BJ is reliable, stable and effective in evaluating adult OSAHS cognitive function. MoCA-BJ can detect cognitive dysfunction through visual space, executive ability and total score, while distinguishing healthy controls and OSAHS patients from attention, language total score, language repetition, delayed recall, but can not distinguish between severe and non-severe OSAHS patients. In addition, Orientation in the distinction between normal controls and severe patients, severe and non-severe patients play a role, but can not distinguish between normal controls and OSAHS patients. PMID- 29798211 TI - [Effects of nasal polyps and allergy rhinitis on quantitative evaluation of subjective and objective assessment of chronic rhinosinusitis]. AB - Objective:To investigate the effect of nasal polyps and allergy rhinitis on disease assessment of chronic rhinosinusitis, and to analyze the correlation between subjective and objective scores. Method:A total of 253 patients with chronic rhinosinusitis were enrolled from June 2016 to June 2017, and the clinical data such as sex, age, comorbidity, diagnosis and treatment were summarized. All patients were grouped as with or without nasal polyps, with or without eosinophilia, with or without allergic rhinitis group, and assessed by the visual analogue scale(VAS), Lund-Mackay CT score and Lund-Kennedy score respectively. The difference of the three grades in each group were analyzed by statistic analysis. The correlation between the three grades was analyzed. Result:Two hundred and fifty-three cases of chronic rhinosinusitis were included in the analysis. There were 143 males and 110 females with an average age of 44.44+/-15.44 years old, mostly in the 41-65 age group, and the difference was statistically significant (P<0.01). The scores of VAS, Lund-Mackay CT and Lund Kennedy in the nasal polyp group were significantly higher than those in the non nasal polyp group (P<0.05). The nasal endoscopy score of patients with allergic rhinitis was higher than that of non-allergic rhinitis group (P<0.01). There was no significant difference between VAS score, CT and endoscopic score in EOS group (P>0.05). There was a positive correlation between VAS score and nasal endoscopy score or CT score (P<0.01) in patients of non-allergic rhinitis or eosinophilia group, but there was no correlation (P>0.05) in patients with allergic rhinitis or eosinophilia group. There was no correlation when two or three factors exist at the same time beteen the nasal polyp, allergic rhinitis and EOS group (P>0.05), whereas show up positive correlation on non-merged group (P<0.01). Conclusion:Chronic rhinosinusitis complicated with nasal polyps or allergic rhinitis can significantly increase the subjective and objective symptoms of patients. There are differences between subjective symptoms and objective tests in the patients with nasal polyps, allergic rhinitis and EOS factors. Therefore, clinical attention should be paid to the impact of allergic factors on patients, using a variety of subjective and objective evaluation atrategies to evaluate the condition of patients with chronic rhinosinusitis comprehensively, to provide a basis for personalized diagnosis and treatment. PMID- 29798213 TI - [Aeroallergen spectrum for patients with allergic rhinitis in Chongqing]. AB - Objective:To determine the distribution characteristics of inhaled allergens and its influencing factors among allergic rhinitis (AR) patients in Chongqing. Method:Intracutaneous test was carried out in 2 474 AR patients. All the cases were divided into six groups according to age, 6-13 years old, >13-18 years old, >18-29 years old, >29-39 years old, >39-49 years old, >49 years old and four groups on the basis of season (spring, summer, autumn, winter). The correlations between the positive rates and gender, age, season were analyzed. Result:The most common allergens were dermatophagoides farin (71.26%), dermatophagoides pteronyssinus (73.61%) and polyvalent insect (60.79%). There was no significant correlation between most allergens and gender(P>0.05). Statistical analysis was conducted among different age groups, it showed that the positive rates of overwhelming majority allergens were highest in the group of 13-18 years old and higher in 6-13 years old group, and then gradually declined with age with a striking difference in each groups (P<0.05). Similar analysis was carried out among the groups in four seasons. It revealed that the prevalence rates of most allergens were higher in summer and autumn than that in spring and winter (P<0.05). Conclusion:Dermatophagoides and polyvalent insect are the most prevalent inhalant allergens in AR disease in Chongqing. Most AR patients had multiple allergens. The prevalence rates of most allergens were significantly different with age and season. PMID- 29798214 TI - [Initial observations of inlay "butterfly" cartilage tympanoplasty]. PMID- 29798215 TI - [The influence of cold dry air on nasal mucosa]. AB - Nonspecific nasal hyperreactivity (NHR) has been widespread observed in patients with allergic rhinitis (AR) and nonallergic rhinitis (NAR). As a clinical hallmark, NHR is more common in patients with NAR. The cold dry air (CDA) can stimulate nasal symptoms such as rhinorrhea and nasal obstruction, and the CDA provocation test can be used as a reliable objective method to evaluate NHR. The mechanism of CDA-induced nasal symptoms is very complicated and thus it has not yet been fully illuminated. The innervation of the nasal nerves includes sensory nerve (trigeminal ganglion), sympathetic nerve (superior cervical ganglion) and parasympathetic nerve (sphenopalatine ganglion). CDA innervation may also be associated with these nerves and associated signal pathway. Recently, general attention has been focused on the transient receptor potential (TRP) channel, including TRP vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1). More relevant researches are needed to further clarify the mechanism. PMID- 29798216 TI - [Research progress of amphiregulin and its role in airway inflammatory disease]. AB - Amphiregulin is a member of epidermal growth factor family, and is also one of the ligand of epidermal growth factor receptor, it participates in many physiological and pathological process by combining with EGFR. Researches have proved that AREG participates in asthma and airway inflammatory diseases caused by smoking and PM 2.5, and AREG plays an important role in the process of airway remodeling and inflammation. This paper mainly reviews the expression and function of AREG, and focus on it's research status in airway inflammatory disease. PMID- 29798217 TI - [Enviroment control and healthy education: the most important methods for treatment of allergic rhinitis]. PMID- 29798218 TI - [Keypoints of the EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivits (draft)]. PMID- 29798219 TI - [Treatment of allergic rhinitis-What can we do in allergen control for house dust and pollens?] PMID- 29798220 TI - [Allergic rhinitis management:environment control and patient education]. PMID- 29798221 TI - [Allergic rhinitis management:environment control and patient education]. AB - Objective:To observe the auxiliary curative effect of combined clostridium and bifidobacterium capsules, live (also called Changlekang) in the treatment of allergic rhinitis by comparing IL-10, transforming growth factor-beta1(TGF beta1), the quality of life score and symptom score before and after oral Changlekang.Method:Twenty qualified patients in the study group and 20 qualified patients in the control group were enrolled.The study group was given changlekang, desloratadine citrate disodium tablets and mometasone furoate nasal spray for treatment. After 2 weeks of treatment, Changlekang was still given for maintenance therapy for 6 weeks, and no other two kinds of drugs. The control group was given the desloratadine citrate disodium tablets and mometasone furoate nasal spray for 2 weeks and then quited the clinical trials. The changes of symptom score, quality of life score, serum IL-10, serum TGF-beta1 would be statistically analyzed during the treatment.Result:1Before treatment, serum TGF beta1 and IL-10 of normal group was significantly different from the study group and the control group (P< 0.001), and the study group and the control group's were significantly lower than the normal group.2With the increase of treatment time, serum IL-10, TGF-beta1 levels of patients in the study group increased gradually. Four point method ocular symptoms score, VAS ocular symptoms score and total score of RQLQ decreased gradually; 3patients in the control group after 2 weeks'treatment, serum IL-10, TGF-beta1 was higher than that before treatment (P< 0.001), at the same time all symptom scores, total score of RQLQ were lower than those before treatment (P< 0.001). 4After 2 weeks' treatment, patients in the study group, the serum IL-10 is higher than that of control group (P< 0.001); 5Before treatment serum IL-10, TGF-beta1 of AR patients might have little correlation with symptom scores, total score of RQLQ on linear (P> 0.05).Conclusion:1serum IL-10, TGF-beta1 levels of AR patients may be lower thannormal, and IL-10, TGF-beta1 may be involved in the pathogenesis of AR. 2Changlekang may increase the production of serum IL-10, TGF-beta1 in AR patients. 3AR patients with desloratadine citrate and mometasone furoate nasal spray treatment combined with Canglekang may promote higher serum IL-10 production than conventional two combination therapy, but there is no more significant improvement in symptoms score and quality of life score. 4Changlekang may improve ocular symptoms and the quality of life in AR patients. 5Before treatment serum IL-10, TGF-beta1 of AR patients may have little correlation with symptom scores, total score of RQLQ, as a result the level of serum IL-10 and TGF beta1 can not be used to evaluate the severity of AR for the time being. PMID- 29798222 TI - [The advances of probiotics treatment of allergic rhinitis]. AB - In recent years, the prevalence of allergic rhinitis faces an explosion. People's understanding about the pathogenesis of this disease goes profound. Probiotics is competent to regulate the balance of immune system, and also can reduce susceptibility towards allergens. Now it is right a hot topic that applying probiotics to remedy allergic rhinitis. Since the data of many researches in this field is at hand, further discuss is needed from experimental methods to molecular mechanisms. PMID- 29798223 TI - [Interpretation of allergic rhinitis and its impact on asthma (ARIA)]. AB - Allergic rhinitis and its impact on asthma (ARIA) has been the most preferred reference for national guidelines. The ARIA 2010 revision is the first evidence based clinical guideline in the field of allergies, which has great influence in the world. The ARIA 2016 revision continues the basic framework of the 2010 revision, which focuses on six controversial clinical issues in the treatment of allergic rhinitis.It aimed to provide clear informationand systematic treatment for patients, clinicians and health policy makers. The interpretation of the ARIA 2016 revision will help domestic otolaryngologist, respiratory doctors, and allergy practitioners understand the latest guidelines for AR drug treatment in the world. PMID- 29798224 TI - [Drug-taking behavioral analysis in patients with allergic rhinitis]. AB - Objective:To analyze the drug-taking behavior of patients with allergic rhinitis, and the relationship with the severity of the symptoms.Method:A total of 1 621 sets of data in 66 patients with allergic rhinitis were enrolled in this study, who filled out the daily symptom score scale and daily medication score scale for 5 days or more. The symptoms include sneezing, rhinorrhea, nasal itching, nasal congestion, eye itching/foreign body sensation/red eyes and watery eyes were scored. The medications include antihistamines, nasal glucocorticoid, oral glucocorticoid, beta2 receptor agonists and inhaled glucocorticoid were scored.Result:In the 1 621 sets of data, the highest incidence of symptoms was sneezing, 50.77%, the highest incidence of moderate to severe symptoms was rhinorrhea, 10.06%. The drug-taking behavior was 827 times, and the drug?taking rate was 51.02%. Antihistamines had the highest use ratio, 73.64%, followed by nasal glucocorticoid, 49.33%. There was no direct relationship between the total symptom score and the drug-taking rate, nasal glucocorticoid use ratio. Compared with the group of continuous drug-taking less than 2 weeks, the total symptom score of the group of continuous drug-taking more than 2 weeks was significant low.Conclusion:The number and continuity of the drug?taking in patients with allergic rhinitis vary greatly. Patient education is needed. PMID- 29798225 TI - [The study of locating facial nerve precisely in middle ear surgery based on clinical anatomy]. AB - Objective:To investigate the methods of locating facial nerve precisely in middle ear surgery through the observation and measurement of the facial nerve and surrounding anatomical structures and to provide reference for the middle ear surgery.Method:Combined surgical approach on 15 cases (30 sides) fresh adult cadaveric specimens were dissected, observed the characteristics of facial nerve and its shape and spatial relationship of the surrounding structures, and measured the distance between the facial nerve and its surrounding structures.Result:The shortest distance from the midpoint of the posterior wall of external auditory canal (annulus level) to the vertical segment of the facial nerve was (3.37+/-0.34)mm, the shortest distance from the leading edge of the sigmoid sinus to the vertical segment of facial nerve was (7.40+/-0.71)mm, the shortest distance from the lateral margin of jugular bulb to the facial nerve was (5.58+/-0.79)mm, the shortest distance from Henle crest to the pyramidal segment of facial nerve was (12.76+/-1.24)mm, the shortest distance between the pyramidal segment of facial nerve and the posterior short limb of incus was (1.56+/ 0.35)mm, the shortest distance between the pyramidal segment of facial nerve and the lower edge of posterior semicircular canal was (2.56+/-0.41) mm, the shortest distance between the lower edge of horizontal semicircular canal and the horizontal segment of facial nerve was (1.28+/-0.32) mm, the shortest distance between the upper edge of vestibular window and the horizontal segment of facial nerve was (0.67+/-0.15)mm.Conclusion:A good command of the anatomy of temporal bone as well as the methods of locating facial nerve will provide the key to reduce the probability of iatrogenic facial nerve injury in middle ear surgery. PMID- 29798226 TI - [Diagnosis value with Xpert Mtb/RIF assay for cervical tuberculous lymphadenitis]. AB - Objective:To evaluate the accuracy of Xpert MTB/RIF assay in the diagnosis of cervical tuberculous lymphadenitis.Method:A total of 160 patients with cervical lymph node tuberculosis confirmed by pathology in Wuhan Pulmonary Hospital between January 2015 and June 2016 were enrolled. Cervical lymph node biopsy tissue specimens from these patients were collected and tested with acid-fast bacilli smear, TB-DNA assays, culture, and Xpert Mtb/RIF, respectively. The results were analyzed using SPSS 17.0 statistical software.Result:Using pathological diagnosis as the standard, the sensitivity of acid-fast bacilli smear was 8.12%(13/160), the sensitivity of TB-DNA assay was 69.38%(111/160), the sensitivity of culture was 31.88%(51/160), and the sensitivity of Xpert Mtb/RIF was 74.38%(119/160). The detection rate of multidrug-resistant lymphoid tuberculosis using a combination of Xpert Mtb/RIF, line probe assay (LPA), and culture methods was 9.38%(15/160).Conclusion:Xpert Mtb/RIF can rapidly detect cervical lymph node tuberculosis and assess rifampicin resistance. TB-DNA assay exhibited similar sensitivity as compared to Xpert Mtb/RIF and can detect both isoniazid and rifampicin resistant genes through LPA.These two methods are more effective than the traditional culture and smear methods. PMID- 29798228 TI - [The application of tragal cartilage-perichondrium in open method tympanoplasty]. AB - Objective:To investigate the efficacy of the application of tragus cartilage perichondrium in open method tympanoplasty.Method:Thirty patients with middle ear cholesteatoma were treated with open method tympanoplasty and titanium ossicular prosthesis replacement surgery utilized the tragus cartilage-perichondrium, the air-bone gap and the recovery of tympanic membrane were observed before and after operation.Result:Thirty ears achieved primary healing. After a follow-up of 12 months, no prosthesis extrusion and atticus lateral wall collapse were observed. The average air-bone gaps reduced by 13 dB in average.Conclusion:The tragus cartilage-perichondrium is an appropriate material in open method tympanoplasty. PMID- 29798227 TI - [Comparative study of surgical treatment combined with various methods for treatment of ear scar]. AB - Objective:To evaluate the clinical effect of auricular keloids resection combined with local injection of glucocorticoid and superficial X-ray treatment in order to identify a surgery-based, personalized, comprehensive treatment system.Method:One hundred and sixty patients with auricular keloids were divided into four groups: surgery group, surgery combined with local injection of glucocorticoid group, surgery combined with superficial X-ray group and surgery combined with glucocorticoid and electron irradiation group (Triple therapy group). These groups were followed up for one year. Based on Darzi's criterion of keloid curative effect, the effect was judged and analyzed statistically.Result:One year after operation, the effective rate of the surgery group was 52.5%, that of the surgery combined with glucocorticoid injection group was 80.0%, that of the surgery combined with the superficial X-ray group was 82.5%, and that of the triple therapy group was about 97.5%. The simple surgery group was significantly lower than the surgery combined with glucocorticoid injection group, the operation combined with superficial X-ray group and triple therapy group (P< 0.01); the triple therapy group was better than the surgery combined with superficial X-ray group and surgery combined with glucocorticoid injection group, showing statistically significant differences (P< 0.05); There was no statistical difference (P> 0.05) between the surgery combined with glucocorticoid injection group and the surgery combined with superficial X-ray group.Conclusion:In the auricular keloids treatment, surgical resection with a poor curative effect is not recommended; triple therapy, which is better surgery combined with glucocorticoid local injection and surgery combined with superficial X-ray, should be used as the first line treatment. The overall response rate of surgery combined with glucocorticoid local injection and surgery combined with superficial X-ray is satisfactory. It should be individualized for use depending upon the situation. PMID- 29798229 TI - [Effects of exogenous brain-derived neurotrophic factor on the morphology and function of cochlea in the animal model of hereditary hearing loss]. AB - Objective:To study the effect of early administration exogenous BDNF on the morphology and function of conditional knockout Cx26 mice cochlea.Method:Conditional knockout Cx26 mice was chosen as animal model, early after birth (P0-P2) exogenous BDNF (rAAV mediated BDNF plasmid, AAV-BDNF) was injected through scala media. Expression of BDNF in the cochlea was observed by western-blot, the growth promoting effect of nerve fibers was detected by IHC; 2 m after injection, the protective effect of BDNF on corti and spiral ganglion cells were detected by resin section; animal hearing were tested by ABR.Result:1Exogenous BDNF could be well expressed in the inner ear; 2Exogenous BDNF has a good effect on the growth of cochlea nerve fiber; 3Exogenous BDNF could protect the morphology of organ of corti; to count the number of spiral ganglion cells, using the density value of top-turn in non-injected ear as the standard unit, the values of middle and basal turn in injected ear were 0.81+/ 0.02, 0.65+/-0.02, compared with non-injected ears, both statistically significant difference could be found, indicates that exogenous BDNF can effectively improve the number of spiral ganglion cells. 4By calculating the ABR threshold of different frequencies of the injected and non-injected ear, there was no statistical difference between them. Indicates that exogenous BDNF has no effect on improving the function of cochlea.Conclusion:The protective effect of early administration exogenous BDNF was effective in the cochlea and spiral ganglion cells of conditional knockout Cx26 mice, but no protective effect for auditory function. PMID- 29798230 TI - [An analysis of the subcutaneous immunotherapy on the pulmonary function and symptoms of asthma and rhinitis in children]. AB - Objective:To evaluate the effect of subcutaneous immunotherapy on allergic asthma and rhinitis in children.Method:A prospective study was adopted to analysis 3 years SCIT treatment of 144 cases of children with allergic asthma and rhinitis. Before and after SCIT treatment for 1 year, 2 and 3 years, FEV1, daytime and night symptoms of asthma and rhinitis were evaluated.Result:After 3 years of SCIT treatment, the FEV1 had significantly increased (F= 243.05, P< 0.01), and with the duration of the treatment was further improvement (P< 0.01). Compared with the baseline, treatment 1 year in daytime, nighttime symptoms scores of asthma and nighttime symptoms scores of rhinitis had significantly reduced (P< 0.01). All symptoms were reduced further by 2 years of treatment (P< 0.01) compared with 1 year. Compared with the 2 years of treatment, daytime symptoms of asthma and rhinitis of 3 years SCIT treatment was improved significantly (P< 0.05).Conclusion:Subcutaneous immunotherapy with 3 years in children allergic with asthma and rhinitis can play a significant effect. PMID- 29798231 TI - [Computer-assisted anatomical evaluation of the nasal sinuses in 2-3 years old children]. AB - Objective:To analyze the anatomical and developmental characteristics of nasal sinuses in 2-3 years old children.Method:Coronal CT scans of 62 cases (2-3 years old children) were studied with the imaging station. The gasification conditions of the sinuses were identified and measured.Result:The mean of the transverse and vertical diameters for the left side of the maxillary sinuse was (17.51+/-2.92)mm and (16.63+/-3.46)mm. Those for the right side were (17.28+/-2.51)mm and (17.24+/ 3.72)mm. The mean for the left side of the anterior ethmoid sinus were (5.06+/ 1.18)mm and (13.61+/-2.49)mm. Those for its right side were (5.00+/-1.45)mm and (13.64+/-2.30)mm. The mean for the left side of the posterior ethmoid sinus were (7.94+/-1.72)mm and (12.80+/-1.78)mm. Those for the right side were (7.88+/ 1.85)mm and (12.64+/-.96)mm.96.77%(120 sides) of the sphenoid sinuses were developed. The mean for the left side of the sphenoid sinus were (7.38+/-3.11)mm and (8.67+/-3.14)mm. Those for the right side were (7.48+/-2.70)mm and (8.63+/ 2.42)mm. 30.65% (38 sides) of the frontal sinuses were developed.Conclusion:The all nasal sinuses in 2-3 years old children have been already developed. The pneumatization of the frontal sinus was defined in some babies. It can help radiologist make correct diagnosis of paranasal sinuses in children. PMID- 29798232 TI - [The effects of tympanoplasty on improvements of hearing and tinnitus for chronic otitis media patients with tinnitus]. AB - Objective:The purpose of this study is to investigate the correlation of hearing and tinnitus improvement levels in chronic otitis media (COM) patients after tympanoplasty.Method:Thirty-five cases with COM, accompanied with tinnitus on the affected side or undefined sides, were enrolled and accepted for tympanoplasty between May 2015 and Dec 2016. Audiologic evaluation by pure tone audiometry and assessment of Tinnitus Handicap Inventory scores were conducted in pre-operation and 3 months post-operation. The mean air conduction (AC), boneconduction (BC), air-bone gap (ABG) at 500, 1 000, 2 000 and 4 000 Hz was calculated. THI scores were recorded and analyzed.Result:All the patients healed well and the felthearing was improved and tinnitus symptoms alleviated. There was a significant difference between post-operative THI score (15.0+/-5.6) and pre operative score (21.2+/-7.4), t= 7.8, P< 0.01. Significant differenceswerealso found in comparison of pre-operative AC (41.6+/-9.9)dBHL and post-operative AC(32.5+/-10.0)dBHL, t= 5.9, P< 0.01, pre-operative ABG (27.0+/-7.4)dBHL and post operative ABG (18.3+/-7.7)dBHL,t= 6.5, P< 0.01. However, the value of BC in the pre-operation (14.5+/-5.9)dBHL was almost the same as that in post operation(13.9+/-6.0)dBHL, t= 1.2, P> 0.05. Hearing improve levels aboutAC and ABG were positively correlated with the remission degree of tinnitus post operatively (t= 0.9, P< 0.01).Conclusion:Patients accompanied with tinnitus experienced a remarkableremission in tinnitus and recoveryin hearing levelfollowed bytympanoplasty.Tympanoplasty was a positive treatment for relievingtinnitus in COM patients. PMID- 29798234 TI - [The curative effect observation of nasal irrigation by hypertonic salinein treatment of infant acute rhinosinusitis]. PMID- 29798233 TI - [The efficacy of thyroid hormone replacement therapy in patients with hypothyroidism and OSAHS: a Meta analysis]. AB - Objective:To systematically evaluate the impact of thyroid hormone replacement in patients with OSAHS and hypothyroidism.Method:The related case-control study of thyroid hormone replacement in patients with OSAHS and hypothyroidism had been searched from Cochrane Library, PubMed, CNKI, Chinese Biomedical Literature Database, Wanfang Resource Database.The case-control study which were in line with the condition need to be evaluated the quality and to be extracted in literature. The RevMan 5.3 and STATA softwares were applied to carry out the Meta analysis.Result:Seven literatures of case-control study were included. The Meta analysis showed that: After the thyroid hormone replacement, the patient's AHI index, TSH index, LSaO2 index were significantly improved (P< 0.05). The AHI index statistical results of the patients were [SMD= 3.15, 95%CI: (4.36-1.94), P< 0.000 01; I2= 96%], TSH index were [SMD= 4.15,95%CI: (1.15-7.15), P= 0.007; I2= 99%], LSaO2 index were [SMD=-1.08, 95%CI: (-1.46--0.70), P< 0.000 01, I2= 68%].Conclusion:The use of thyroid hormone replacement can effectively reduce the patient's hypothyroidism symptoms and AHI symptoms. PMID- 29798235 TI - [Study on differential diagnosis of upper digestive tract bleeding and epistaxis by placing Foley tube]. PMID- 29798236 TI - [Huge glass foreign body penetrating into the infratemporal fossa through the maxillary sinus:a case report]. AB - We report a rare case of glass foreign body penetrating into the infratemporal fossa through the maxillary sinus. The patient felt a little difficulty to open mouth. Both CT and DSA are helpful in diagnosis and treatment. It was important to keep the foreign body stability and integrity, through the modified Weber incision around the original traumatic wound and removal of anterior wall of the maxillary sinus around the foreign body. PMID- 29798238 TI - [Obstructive sleep apnea hypopnea syndrome study on pathogenesis and prognosis]. AB - OSAHS is a common disease during sleep and its pathogenesis is complex. The anatomic level of upper airway is a more recognized pathogenic factor. Recent studies have shown that nonanatomic factors, such as insufficiency in dilation muscles of upper airway, high loop gain and low arousal threshold, play an important role in the pathogenesis of OSAHS. This paper revives the latest literature home and abroad on the anatomical and nonanatomical factors in the pathogenesis of OSAHS and makes a systemic review. PMID- 29798237 TI - [Wry nose and rhinolith: a case report]. AB - This report described a case of the wry nose and rhinolith patients. A 25 years old female patient complained a sense of persistent left side of nasal congestion runny with 10 years. During the 10 years the symptom repeatedly occurrence, aggravated with peculiar smell of 1 months. A combined treatment including endoscopic sinus surgery with correction of the deviated nose and removal of nasal stone was performed in the patient.Three monthsafter operation, the patient recovered well, without recurrence, external nasal deformity, foreign bodies remain. PMID- 29798239 TI - [Expression and significance of growth differentiation factor 15 and MUC5AC in chronic rhinosinusitis]. AB - Objective:To investigate the expression of growth factor differentiation factor 15 (GDF15) in the nasal mucosa of patients with chronic rhinosinusitis (CRS) and its relationship with mucin 5AC(MUC5AC).Method:Fifteen patients with CRS and nasal polyps, 15 patients with CRS without nasal polyps and 15 patients with normal nasal mucosa were enrolled in the study. Hisological changes of sinonasal mucosa were examined by hematoxylin and eosin (HE) stainding. The expression of total mucins was evaluated by periodic acid Schiff staining(PAS). And the expression of GDF15 and MUC5AC were measured by immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR).Result:The tissuse samples demonstrated mucaosal thicking, goblet cell hyperplasia, glandular hyperplasia and inflammatory cell infiltration in CRSwNP and CRSsNP. IHC revealed that GDF15 and MUC5AC expression higher in CRSwNP and CRSsNP than in normal sinus mucosa (P< 0.05). qRT-PCR also displays that the relative expression levles of mRNA exprssion of GDF15 and MUC5AC were higher in CRSwNP and CRSsNP than in controls.And the expression level of GDF15 was positively correlated with that of MUC5AC mRNA in CRS.Conclusion:GDF15 and MUC5AC were upregulated in CRS with or without nasal polyps, indicating that GDF15 is an important factor in the process of hypersecretion of MU5AC in CRS. PMID- 29798241 TI - [Effects of voice therapy and psychological intervention on anxious and depressive in patients with voice disorders]. AB - Objective:To investigate the expression of miR 34a in epithelial cells of nasal polyps (NPs) and to determine its effects on hypoxia induced epithelial mesenchymal transition (EMT).method:Nasal epithelial cells (NECs) were collected from NPs and normal inferior turbinates. miR-34a expression was detected by means of quantitative reverse transcriptase polymerase chain reaction. In addition, normal NECs were cultured under normoxia/hypoxia conditons. The effects of miR 34a mimics on hypoxia induced EMT were investigated.result:miR-34a was specifically down-regulated in NECs of NP. Hypoxia decreased miR-34a expression in vitro. Furthermore, E-cadherin and alpha-SMA were down-regulated and up regulated, respectively. miR-34a mimics transfection can reverse this process.Conclusion:miR-34a suppress hypoxia-induced EMT in NECs. The down regulation of miR-34a may contribute to nasal polypogenesis. PMID- 29798240 TI - [Effects of voice therapy and psychological intervention on anxious and depressive in patients with voice disorders]. AB - Objective:To investigatethe effect of voice therapy on anxious and depressive in patients with voice disorders.Method:The patients who received voicee therapy in our department from May 2014 to July 2016 were enrolled in our study and evaluated by self-rating anxiety scale (SAS) and self rating depression scale (SDS), before and after voice therapy.result:Before voicee therapy, the score of SAS and SDS were 47.52+/-11.15 and 48.63+/-8.70 respectively, which were higher than domestic norm (37.23+/-12.59 and 41.88+/-10.57 for SAS and SDS, respecative) with P< 0.05. After voice therapy, the score of SAS and SDS were 38.03+/-6.95 and 42.21+/-7.71, which were lower than the score of before voice therapy (P< 0.05). And compared with the domestic norm, the difference was not statistically significant (P> 0.05).Conclusion:The anxiety and depression scores of patients with voice disorders are higher than those of ordinary people. The voice therapy can effectively relieve anxiety and depression of patients with voice disease. PMID- 29798242 TI - [Effect of pretreatment serum LDH and ALP levels on the prognosis of patients with nasopharyngeal carcinoma]. AB - Objective:To investigate the effects of serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (ALP) levels on the prognosis of patients with nasopharyngeal carcinoma (NPC) before treatment.Method:Three hundred and thirty nine NPC cases, who were firstly treated in our hospital from April 2006 to October 2008, were enrolled in our study. Association of overall survival (OS) rate and disease-free survival (DFS) rate with clinical characteristics (age, gender, Tclassification, Nclassification, clinicalstage, radio therapy methods, radio therapy dose, the levels of pretreatment serum LDH) were evaluated using univariate and multivariate analysis methods.Result:Univariate analysis showed that age, clinical stage, pretreatment LDH level were significantly associated with OS and DFS of NPC. And multivariate analysis revealed that age, clinical stage and pretreatment LDH level were independent factors for OS and DFS.Conclusion:Age, clinical stage and the levels of pretreatment LDH level may be independent prognostic factorsto predict recurrence and death of NPC. PMID- 29798243 TI - [The characteristic of vestibular ocular reflex in patients with vestibular migraine]. AB - Objective:Analysis of vestibular ocular reflex (VOR) in patients with vestibular migraine (VM) by vestibular autorotation test (VAT). To explore the clinical value of VAT technology in the diagnosis of vestibular migraine.Method:Sixty-nine patients with VM, 73 patients with posterior circulation (PCI) vertigo and 65 normal people were examined by VAT test. The characteristics of vestibular ocular reflex were analyzed by using VAT gain, phase and asymmetry among them.Result:1Among the 69 cases of VM patients,54 cases (78.3%) were horizontal or vertical gain abnormalities, 66 cases (95.7%) were horizontal or/and vertical phase delay, and 13 cases (18.8%) were asymmetric abnormalities. 2Among the 54 (78.3%) cases of abnormal gain, 46 (66.7%) cases demonstrated high gain, 42 had high gain combined with high phase, and 36 cases were simple horizontal high gain (and mainly concentrated at 2-4 Hz, 26 cases), 8 cases (11.6%) showed low gain. 3VAT characteristics in PCI group:47 cases (64.4%) were high gain, and 11 cases (15.1%) were low gain. There was no significant difference in high gain and low gain between PCI group and VM group (chi2 was 0.07 and 0.37, P>0.05). Both VM group and PCI group are high-gain, but there was significant difference in the phase delay and asymmetric indicators. 4VAT characteristics in normal people group: The four indices have low abnormally positive rates. There were statistically significant differences of the high gain and the low gain between the normal people group and VM group(chi2 were 56.17 and 97.57, P<0.01).Conclusion:The vestibular ocular reflex of VM is high-gain based and was mostly in the 2-4 Hz frequency,and accompanied by phase delay. Vestibular central system was mainly involved in VM. VAT detection can provide a clue for VM diagnostics. PMID- 29798245 TI - [Retrospective analysis of the four kinds of virus in adeno tonsillar tissues from children using PCR]. AB - Objective:To investigate the seasonal disturbations and the rates of detection of Epstein?Barr virus (EBV), Human Bocavirus(HBoV), and polyomaviruses KI and WU (KIPyV and WUPyV) in adenoid and tonsil tissues during the absence of acute infection symptoms.Method:DNA expressions of EBV, HBoV, polyomaviruses KIPyV and WUPyV were investigated in children with chronic tonsillar and adenoidal diseases using real time polymerase chain reaction. The patients were divided into three group: adenoid group, chronic tonsillit group and hypertrophic tonsillitis group. The relationships of the expressions of these viruses with age, gender, recurrent infection and airway obstruction were analyzed. Seasonal variations in rates of detection of these viruses in adenoid and tonsil tissues were also investigated.Result:Considering adenoid specimens, HBoV was found to be the most frequent virus with the rate of 43.1%. In specimens of chronic tonsillitis and hypertrophic tonsils, EBV was the most frequently encountered virus (53.8%, and 32.0%, respectively). In children with hypertrophic adenoids, while HBoV was detected to be positive throughout the year, EBV was present throughout the year in children with recurrent tonsillitis.Conclusion:The detection of HBoV and EBV throughout the year in samples of children with asymptomatic chronic adenotonsillar diseases may indicate that these viruses may remain persistently in lymphoepithelial tissues of upper respiratory tract. Virus persistence may have a pathogenetic potential for development of lymphoid hypertrophy and a chronic stimulatory effect for inflammation. PMID- 29798244 TI - [Clinical efficacy of of endoscopic assisted open pathway combined with radiotherapy in the treatment of advanced maxillary sinus malignant tumor]. AB - Objective:The aim of this study is to analyze the clinical effect of endoscopic assisted open pathway combined with radiotherapy in the treatment of patients with advanced maxillary sinus malignant tumor.Method:A retrospective analysis was performed on the survival of 29 patients with advanced maxillary sinus malignant tumor treated by endoscopic assisted open approach combined with radiotherapy.Result:A total of twenty nine patients with cancer lesions were successfully resected, of which 7 cases underwent preoperative radiotherapy plus surgery plus postoperative radiotherapy, 22 cases were treated by surgery plus radiotherapy after operation. The median follow up time was 60 months (23-129 months). The 3 year and 5 year survival rate of the patients was 72% and 61%, respectively (90% and 80% was in II stage respectively. 63% and 51% was in III+IV stage respectively).Conclusion:Endoscopic assisted open pathway combined with radiotherapy is an effective method for the treatment of maxillary sinus carcinoma, and it can still be well treated with preoperative radiotherapy in patients with stage IV without distant metastasis. PMID- 29798246 TI - [Clinical analysis of 48 cases of non-invasive fungal sinusitis]. AB - Objective:To analyze the causes, imaging diagnosis, clinical characteristics and clinical effect of the endoscopic surgery of non-invasive fungal rhino sinusitis.Method:A retrospective analysis of 48 patients diagnosed with fungal sinusitis by pathology.Result:Forty-eight cases of 40 cases are fungal sinusitis (40/48), the other 8 cases are allergic fungal rhinosinusitis. The two morphology, imaging, histopathology, treatment and outcome are not the same, more than half of the CT scan and endoscopic examination, have different degrees of anatomical abnormalities (26/28), 25 cases had a long-term frequent using of antibiotics. Postoperative follow-up 1-3 years, cured 43 cases, recurrence 5 cases, which has been cured after re-surgery and other comprehensive treatment. Conclusion: Nasal cavity anatomical abnormalities and the frequent use of antibiotics is closely related to the attack of fungal sinusitis. Sinus CT scane and nasal endoscopy is an important method for the diagnosis of fungal sinusitis, and endoscopic sinus surgery is an effective method of fungal sinusitis. The recurrence rate of allergic fungal sinusitis was higher (5/8), so comprehensive treatment was an importance measure to prevent recurrence. Caution with antibiotics and hormones is to prevent fungal sinusitis occurred in a factor that can not be ignored. PMID- 29798247 TI - [Application of carbon nanoparticle in neck VI lymph node dissection for papillary thyroid carcinoma]. AB - Objective:To investigate the application value of carbon nanoparticle lymph tracer in VI lymph node dissection for papillary thyroid cancer.Method:One hundred and forty-eight patients with papillary thyroid cancer from October 2015 to May 2016 were enrolled into the retrospective analysis. Seventy-five cases with carbon nanoparticle injected in operation were divided into observation group, while the other seventy-three cases without lymph tracer were divided into control group. The number of neck VI lymph nodes and metastatic lymph nodes between the two groups were compared, as well as the incidence of parathyroid injury and postoperative hypocalcemia. Result:There were no significant difference in age, gender, tumor size, pathology or type of operation between the two groups(P>0.05). Parathyroid injury incidence in the observation group significantly lower than the control group (5.33% vs 5.33%, P< 0.05). There was significant difference in the number of neck VI lymph node dissection between the two groups (observation group: 6.51+/-4.65, control group: 4.42+/-3.10, P< 0.05).Conclusion:Carbon nanoparticle injected as a lymph tracer in thyroid surgery is helpful, the characteristics of the parathyroid gland negative imaging can effectively decrease the rate of parathyroid gland injury. PMID- 29798248 TI - [Analysis of the lymphoepithelial carcinoma of the salivary gland: 12 cases report]. AB - Objective:To improve recognization of clinical, imaging and pathological characteristics of lymphoepithelial carcinoma (LEC) of the salivary glands.Method:The clinical manifestations, imaging features, histological and immunohistochemical characteristics of LEC of the salivary glands (n = 12) between 2003 and 2013 were retrospectively reviewed.Result: Four cases of male and 8 cases of female were enrolled, and the average age of 53.25 years. Ten lesions were located in the parotid gland, and 2 cases were in the submandibular gland. Two cases were unilateral multiple tumors, 10 cases were unilateral solitary tumor, 4 cases were with cervical lymph node metastasis and 1 case was with peripheral facial paralysis. Ten patients had positive EB VCA IgA test. Homogeneous density and obvious enhancement were achieved in all lesions on CT scan. 8 cases were with irregular shapes, partially or ill-defined margin, and heterogeneous enhancement. Incomplete capsule was found in 4 cases, while no obvious capsule was found in 6 cases. HE staining showed that the infiltrative tumors were formed by the presence of sheets or nests of epithelial cells and interstitial lymphoid tissue. Immunohistochemistry staining revealed that the epithelial cells were reactive for pan CK, the lymphoid cells showed reactivity for both CD20 and CD3 markers. All cases underwent primary tumor and involved gland resection with ipsilateral neck dissection, and postoperative radiotherapy, and 2 cases combined with postoperative chemotherapy. The 3 year survival rate of patients was 75.0%(9/12), and 3 cases died of local recurrence or (and) distant metastasis within 1-2 years of definite diagnosis.Conclusion: LEC of salivary gland is associated with EB virus infection. Most cases present with unilateral solitary mass, and incidence of regional lymph node involvement is high. The imaging characteristics of tumor seem to be malignant on CT scan in most cases. Treatment includes multimodality therapy including surgical resection, neck dissection, and radiotherapy. Local recurrence and distant metastasis are the main causes of death. PMID- 29798249 TI - [Comparative study of two analgesic methods of postoperative children with tonsillectomy]. AB - Objective:To observe the changes of pain response in two analgesic methodes of postopetative children with tonsillectomy.Method:One hundred and twenty four cases of Children with tonsillectomy were randomly divided into groups A and B (for 60 cases and 64 cases). After the operation, the group A was given patient controlled intravenous analegesia, and the group B was given a small dose (5 mg/kg/sub) of ibuprofen in accordance with the age and weight of the child. FLACC was used for the analgesic score. Check the correlation between white blood cells (WBC), serum c-reactive protein (CRP) and cortisol (COR) concentration.Result:Among the four indicators of pain stress. The best judgement method for he pain performance is FLACC and COR, and the poor judgement method is the result of CRP and WBC. After 4 hours, 24 hours, 36 hours of three periods, FLACC scores of children with group B compared with group A at the same time was statistically significant (P< 0.05). There is no statistical significance between each group. There was statistically significant among the concentration of WBC, CRP and COR etc. There were statistically significant in COR's concentration of 24 hours among group A and B(P< 0.05).Conclusion:The judgment for children with tonsillectomy stress can be used by FLACC pain score and Serum COR concentration. Ibuprofen suspension liquid oral can reduce the stress pain response in children, safety satisfy with postoperative analgesia. PMID- 29798250 TI - [Application of adjacent micro flap in the repair of skin defect in head and face]. AB - Objective:The aim of this study is to sum up the different surgical repair methods and techniques for the skin defect of head and face.Method:A retrospective study on 97 cases of the face and head skin defect caused by trauma and tumor resection in nearly five years, including 37 cases on nasal, 21 cases on cheek, 9 cases on frontal, 13 cases on temporal, and 17 cases on ear. After resecting skin lesion in security boundary, skin defect were repaired by transposition adjacent flap, zone vascular pedicle flap, myocutaneous flap and the mucosal flap.Result:Seventy-one cases of the postoperative flap healed and stitches discharged in a week; 24 cases of flap edge small necrosis in small, one flap occurred most necrosis, and one skin flap occurred infection and necrosis.Conclusion:Facial skin defect can be repaired primarily by various types of micro adjacent flap. Flap survival is closely related to surgical techniques and postoperative treatment. Retroauricular groove flap has been widely used to repair skin defect of multiple regions for ear. PMID- 29798252 TI - [The relationship between 18F-FDG uptake and oncogene in human laryngeal squamous cell carcinoma transplantation tumor animal model]. AB - Objective:The aim of this study is to explore the relationship between [F18] fluoro 2 deoxy d glucose 18F-FDG) uptake and oncogene expression in human laryngeal squamous cell carcinoma (LSCC) transplantation tumor.Method:Ten nude mice were randomly divided into two groups, 5 mice of each group. One group was injected subcutaneously with Hep-2 cells to establish xenograft model, and the other one was injected with HIF-RNAi-Hep-2 cells. All animals were conducted with positron emission tomography computed tomography PET scan. The average tumor T/N ratio was calculated. After PET scanning, tumor tissue was picked off for immunohistochemical examination.Result:The tumor imaging were both clear and there was no significant difference between these two groups (P> 0.05). The expression of hypoxia inducible factor 1 alpha (HIF-1alpha), glucose transporter protein-1 (GLUT-1) and vascular endothelial growth factor (VEGF) were high in Hep 2 group. The expression of HIF-1alpha was lower in HIF-RNAi-Hep-2 group (P< 0.05). But there was no significant difference about the expression of GLUT-1 and VEGF between these two groups (P> 0.05).Conclusion:The oncogenic pathway activated in LSCC is related with the uptake of 18F-FDG. The glycolysis gene and vascular factor maybe play a critical role. PMID- 29798251 TI - [Diagnostic accuracy and safety of US-guided core needle biopsy versus fine needle aspiration biopsy of thyroid nodules: a Meta analysis]. AB - Objective:To evaluate the efficacy and safety of core needle biopsy (CNB) and fine neon needle aspiration biopsy (FNAB) in the diagnosis of thyroid nodules.Method:The CNKI, Wanfang database, China Biomedical Literature Database (CBM), PubMed, Cochrane Library, EMBASE, Web of Science database (the deadline of February 2017) were used to search the literature on CNB and FNABCNB. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and evaluated the quality of the literature, and used RevMan 5.3 software for Meta analysis.Result:The accuracy of the CNB group was higher than that of the FNAB group(RR= 1.14, 95%CI: 1.06-1.22, P< 0.01). Meta analysis showed that the accuracy of CNB group compared with FNAB group was statistically significant the difference was statistically significant. There was no significant difference between the two groups (RR= 0.92, 95%CI:0.67 1.25, P> 0.05).Conclusion:CNB is safe and feasible in the diagnosis of thyroid nodules under the condition of mastery of puncture technique. PMID- 29798253 TI - [Effects of perioperative thermoregulation on patients' body temperature, peripheral circulation and blood coagulation time in patients undergoing elective vertical hemi laryngectomy]. AB - Objective:To compare the effects of different thermal insulation measures on perioperative body temperature, peripheral circulation and blood coagulation time in patients undergoing vertical hemi laryngectomy.Method:Sixty eligible patients with elective vertical hemi laryngectomy were randomly divided into 3 groups: preoperative inflatable heating blanket group (A group, n=20), warmed irrigation group (B group, n=20), and control group (C group, n=20). The core temperature were recorded after entering the operating room, before induction, 20th minute during operation, entering PACU and 2nd hour after operation respectively. Blood samples were got at the end of operation to test pH, lactic acid, PT and APTT. After waking patients' SpO2 and thermal comfort were recorded.Result:The core temperatures at time points of 20th minute during operation and entering PACU were significantly different between C group and A group, C group and B group. There were significant difference in lactic acid, PT, APTT and SpO2 between C group and A group, C group and B group. Patients' thermal comfort in all three groups were different.Conclusion:Inflatable heating blanket during operation combined with using it before operation or fluid warmers during operation for perioperative body temperature protection duringelective vertical partial laryngectomy surgery can effectively prevent perioperative hypothermia, improve peripheral circulation and blood coagulation time changes, improve patients' comfort after operation. PMID- 29798254 TI - [Experimental model study on Li's repositioning maneuver for horizontal semicircular canal benign paroxysmal positional vertigo]. AB - Objective:Based on the standard spatial semicircular canal model, the scientificity and feasibility of Li's repositioning maneuver for horizontal semicircular canal benign paroxysmal positional vertigo were analyzed.Method:The standard space semicircular canal model was established. The significance and shortcomings of each step were analyzed by simulating and observing the Li's repositioning maneuver for horizontal semicircular canal benign paroxysmal positional vertigo.Result:According to the model of semicircular canal, the otoliths of horizontal semicircular canal are more likely to return to the ampulla instead of moving into the utriculus through the semicircular canal after using Li's repositioning maneuver.Conclusion:The experimental model suggests that Li's repositioning maneuver omits the necessary steps of repositioning method, and can not simulate the result of the reposition of otoliths. PMID- 29798255 TI - [Analysis of curative effect on chronic suppurative otitis media by tympanoplasty with or without mastoidectomy]. AB - Objective:Analysis of perforation rate and hearing improvement rate of patients with chronic suppurative otitis media after operation, to observe the effect of tympanoplasty with or without mastoidectomy.Method:Retrospective analysis the clinical data of EENT Hospital of Fudan University from January 2011 to December 2016, 167 cases (ears) by tympanoplasty. According to the surgical approach were divided into simple tympanoplasty in 108 cases (group A), tympanoplasty with mastoidectomy in 59 cases(group B)(CWU in 23 cases, IBM in 11 cases, CWD in 25 cases). Endoscopy and pure tone audiometry after 3 to 6 months, using SPSS19.0 software to compare the difference of tympanic membrane perforation rate and hearing improvement rate. Result:The tympanic membrane perforation rate of group A and group B were 8.33%(9/108) and 5.08%(3/59),there was no significant difference(chi2= 0.604, P> 0.05). The hearing improvement rate of group A and group B were 83.33%(90/108) and 77.97%(46/59), there was no significant difference (chi2= 0.727, P> 0.05).Conclusion:For chronic suppurative otitis media with lesions confined to the mastoid and tympanic sinus, the removal of mastoid lesions in the treatment of tympanic membrane healing and improvement of hearing can not achieve better results than simple tympanoplasty. PMID- 29798257 TI - [Efficacy analysis of transoral endoscopic radiofrequency coblation for early glottic cancer]. PMID- 29798258 TI - [Transcatheter arterial embolization in the treatment of maxillary artery pseudoaneurysm hemorrhage: a case report]. AB - Internal maxillary arterial pseudoaneurysm is a potential complication of maxillofacial surgery. A 34-year old woman with maxillary sinus cancer undergoing multiple endoscopic sinus surgery,and subsequently developed acute massive nasal hemorrhage. She was eventually successfully treated with intravascular embolization. The recurrence of nasal hemorrhage was not observed during a seven month follow up. PMID- 29798256 TI - [Effect of cetylpyridinium chloride Buccal Tablets on perioperative application of OSAHS patients]. AB - Objective:To investigate the effect of Cetylpyridinium Chloride Buccal Tablets on perioperative application of OSAHS patients.Method:Sixty patients of OSAHS were randomly divided into treatment group and control group according to the ratio of 1:1, using randomized single-blind controlled trial. The treatment group was treated with Cetylpyridinium Chloride Buccal Tablets in perioperative period and the control group was not. All patients accepted UPPP. Pharyngeal pain, pharyngeal edema, levels of IL-1, IL-8 and TNF-alpha in saliva were analyzed on the first day, third day and fifth day after surgery.Result:Compared with control group, the pharyngeal pain of treatment group was slighter on the third day and fifth day (P< 0.05). The levels of IL-1beta, IL-8 and TNF-alpha in saliva were lower on the third day and fifth day (P< 0.05).Conclusion:Applying Cetylpyridinium Chloride Buccal Tablets during perioperative period can effectively relieve postoperative pharyngeal pain and inflammatory response in patients with OSAHS. PMID- 29798259 TI - [Minor salivary duct carcinoma of the larynx: a case report]. AB - Salivary duct carcinoma SDC is a rare disease, especially in the larynx. From the pathology point of view, SDC histomorphology is very similar to breast ductal carcinoma. From the immunohistochemistry, epithelial antibodies are positive, but the SMA is negative. From the review of papers, total resection is the first choice for the treatment, but the local recurrence and distant metastasis are the main influence factors for survival rate. Now we still lack the clinical experience for such disease. PMID- 29798260 TI - [Mechanism research progress of miRNA in laryngeal carcinoma]. AB - MiRNA(miR) is a non-coding small RNA of 18 to 24 nucleotides in length.By pairing with 3'UTR of its target mRNA molecule, miRNA regulateS the target mRNA molecule in the translation level or directly lead to its degradation. Each miRNA may target several to several hundred mRNAs, of which 30% of the mRNA is regulated by miRNAs. Some studies have shown that miRNA expression disorders play an important role in the development and progression of various tumors and may be the ideal target for tumor therapy. It has been shown that abnormal expression of RNA (miRNA) plays an important role in the occurrence and development of laryngeal cancer. Wang Ping found 47 kinds of miRNA expression abnormalities in laryngeal cancer tissue with microarray chip detection, that of which high expression were 23 kinds and low expression were 24 kinds. MiRNAs that are abnormally expressed in laryngeal squamous cell carcinoma are expected to be a new marker for early diagnosis of laryngeal cancer. In this review, we summarized the progress in recent three years on the association of miRNA and the biological behaviors of laryngeal cancer. PMID- 29798261 TI - [Issues in the diagnosis and treatment of laryngotracheal stenosis]. PMID- 29798262 TI - [Treatment progress of obstructive sleep apnea hypopnea syndrome]. PMID- 29798263 TI - [Transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoid and upper esophageal lesions]. AB - Objective:To describe the therapeutic effect of transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoidarea and upper esophageal lesions. Method:Transoral endoscopic minimally invastive surgery was carried out in fifteen patients.There were 7 patients with primary tumors on the postcricoid area, including three squamous cell carcinoma(2 cases T2N0M0,1 case T2N2cM0),two cavernous hemangioma, one giant fibrovascular polyp and one recurrent lipofibroma. The transoral endoscopic tumors resection en bloc was performed in all of them. Adjuvant postoperative radiation therapy was applied in cases of cancer, and bilateral neck dissections was performed in the T2N2cM0 case; There were other eight patients with upper esophageal lesions , seven cases dysphagia was caused by stroke and one case was Zenker diverticulum, treated by endoscopic cricopharyngeal myotomy ordiverticulotomy. Result:The en bloc resection endoscopically was achieved in all of patients with tumors on the postcricoid area. All surgical resection margins were negative.The two cases of postcricoid cancer and four benign tumor were followed up 16-30 months and 2-12 months respectively, and all of the cases were not local recurrence. A recent patient with postcricoid cancer had not finished postoperative adjuvant radiation therapy. The endoscopic cricopharyngeal myotomy was effective in 4 out of 7 patients,nasogastric feeding was no longer required.Significant improvement occurred in Zenker diverticulotomy patient, due to the return of physiological deglutition, and Barium swallow study showing disappearance of the diverticulum after one month.The effects of minimally invasive threatment were satisfactory,such as not need tracheotomy and early oral feeding, shorter hospital stay and less postoperative complications. Conclusion:Transoral endoscopic surgery is minimally invastive, safe and effective treatment alternative for some hypopharyngeal postcricoid area and upper esophageal lesions. PMID- 29798264 TI - [Photodynamic therapy by topical drup for the treatment of juvenile onset laryngeal papillomatosis]. AB - Objective:To observe the therapeutic effect of photodynamic therapy(PDT) on the treatment of juvenile onset laryngeal papillomatosis. Method:Twenty-eight cases of children with laryngeal papilloma were treated,only 2 cases for the first time, and the rest were repeatedly treated outside our hospital, the average hospital surgery were more than 4 times. Under self retaining laryngoscope and microscope and endoscope assisted by semiconductor laser and plasma and cold instrument method,visible tumor resection and local affixed deposited 20% 5 aminolevulinic acid(photosensitizer) 3 hours later, with 635 nm semiconductor laser photodynamic,200-280 mW and can volume density of 80 to 120 J/cm2, 20 min irradiation. PDT should be repeated after 25 days until no visible tumor.Then,2 times PDT must be done. Result:In 28 cases, 24 cases were followed up for more than 1 years(12 cases were followed up for 3 years),19 had no recurrence, the cure rate was 79.2%(19/24);5 cases recurrence, and the recurrence rate was 20.8%(5/24),among them,2 cases were abandoned because of the relapse,the other 3 cases were cure after 3 times of PDT.The main complications were adhesion of larynx. Conclusion:The preliminary effect of PDT by topical drug for the treatment of juvenile onset laryngeal papillomatosis is encouraging. The principle of PDT and the principle of the recurrence of laryngeal papilloma in children were also introduced in this paper. PMID- 29798265 TI - [Effect of balloon dilation tracheoplasty in the management of acquired subglottic stenosis in children]. AB - Objective:To assess the efficiency and safety of balloon dilation tracheoplasty technique in the management of acquired subglottic stenosis in children. Method:Twenty-three cases were diagnosed as acquired subglottic stenosis by chest CT scan and bronchoscpy,and received the treatment of the balloon dilatation tracheoplasty.The data about the efficiency,complication and prognosis of the treatment were collected. Result:In the 23 cases,6 of All 11 patients with tracheotomy were decannulated,11 patients were successfully managed without tracheotomy,1 patients received laryngotracheal reconstruction(LTR) surgery, 5 cases were still under observation. The overall response rate was 73.91%.All cases were divided into three stages according to Cotton stage system:1 cases were stage I stenosis,6 cases were stage II and 16 cases were stage III. The response rate was 100.00%,83.33%,and 68.75% respectively. The most common complication in the balloon dilatation tracheoplasty was restenosis. Restenosis occurs in 12(52.17%) cases who received more than 1 dilation procedures in this study. Over all average dilation times is 1.87. Eight cases(88.9%) of 9 in fresh leision group were recoverd, the average dilation time is 1.22; 8 cases (57.14%) of 14 in old leision group were recoverd, the average dilation time is 2.23. The average dilation time between two group is significant(P<0.05). Conclusion:Subglottic stenosis in pediatric patients can be successfully managed with balloon dilation tracheoplasty. In patients without prior tracheotomy, tracheotomy can often be safely avoided with appropriate postoperative management. PMID- 29798266 TI - [Clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy]. AB - Objective:To investigate the clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy. Method:The study included 555 cases of vocal fold leukoplakia. All patients received surgical treatment. The relationship between the clinical and pathological features, and influential factors of recurrence and malignancy were analyzed. Result:The pathological types included squamous epithelial simple hyperplasia in 58.0%, mild hyperplasia in 15.5%, moderate hyperplasia in 10.1%, severe hyperplasia and carcinoma in situ in 8.1%, infiltrative carcinoma in 8.3%. The different pathological types varied among different ages significantly(P<0.01). The tobacco and alcohol abuse had no relationship with pathological types(P>0.05). The more severe the pathology were, the more decreasing of the mucosal waves would be(P<0.01). The pathologic severity had an apparent correlation with p53 positivity and the level of p53 and Ki67 positivity. The p53 positive proportion may increase with the increasing pathological severity(P<0.01), so were the p53 and Ki67 positive levels(P<0.01).Among 232 cases of post?operation follow-ups, 83 cases(35.8%) relapsed while 8 cases(3.4%) malignancy. Bilateral lesions had a higher rate of relapse and malignancy than unilateral lesions(95%CIOR 0.378 [0.197-0.723],P<0.01). The relapse and malignancy had a relationship with the pathologic severity. The incidence of disease recurrence and malignancy were positively correlated with pathological severity(P<0.05). p16 positive patients relapsed for more times(P<0.01) and with an uprising tendency of relapse and malignancy(P>0.05). Conclusion:Pathological types of vocal fold leukoplakia are different. The older men, decreasing of mucosal wave of vocal folds and bilateral lesions were very important factors to predict disease severity. p53 and Ki67 positive rating and pathological severity were positively correlated. The bilateral lesions, pathological severity and p16 positivity had a tendency to increasing relapse and malignancy. PMID- 29798267 TI - [The role of laryngopharyngeal reflux in the pathogenesis of Reinke's edema]. AB - Objective:To determine the significance of laryngopharyngeal reflux(LPR) in Reinke's edema. Method:Sixteen patients who have been diagnosed as Reinke's edema between February 2014 to June 2016 were included in this study. The control group included fifty vocal cord leukoplakia and early glottic cancer patients for the corresponding period. RSI,RFS,numbers of laryngopharyngeal acid reflux events,and time of laryngopharyngeal acid exposure were evaluated between two groups. Result:The mean RSI of the Reinke's edema was 11.2+/-3.8,the mean RFS was 8.2+/ 1.5,the median numbers of laryngopharyngeal acid reflux events was 4.0[0.0;9.0],the time of laryngopharyngeal acid exposure was 5.6[0.0;16.7]min.The rate of LPR positive in Reinke's edema patients was 100.0%(16/16)by RSI and RFS,56.2%(9/16)by 24 hour MII-pH monitoring.The mean RSI of the control group was 8.6+/-3.2,the mean RFS was 6.8+/-2.1,the median numbers of laryngopharyngeal acid reflux events was 0.0[0.0;3.0],the time of laryngopharyngeal acid exposure was 0.0[0.0;4.3]min.The rate of LPR positive in control group was 58.0%(29/50)by RSI and RFS,28.0%(14/50)by 24 hour MII-pH monitoring.There were statistically significance in RSI,RFS,numbers of laryngopharyngeal acid reflux events,and time of laryngopharyngeal acid exposure between two groups(P<0.01 or P<0.05). Conclusion:Laryngopharyngeal reflux might play a role as an etiologic factor in Reinke's edema,awareness should increase about acid suppression therapy in Reinke's edema. PMID- 29798268 TI - [Effect of fixation of superior mallear ligament and anterior mallear ligament on the middle ear transfer function-finite element modeling]. AB - Objective:To study the effect of fixation of superiormallear ligament (SML) and anterior mallear ligament(AML) on the middle ear transfer function. Method:A middle ear finite element model was established using micro-CT scanning from an adult temporal bone with normal middle ear structure. And the fixation model of SML and AML were established by changing its Young's modulus. Calculation of fixation and detachment of the two ligaments on the middle ear transfer function. Result:Displacement of tympanic membrane and stapes footplate was decreased significantly in case of fixation in both AML and SML, especially in the low frequency region.The SML fixation increased the amplitude of the stapes footplate by 3 dB between 1-2 kHz. In case of SML fixation along and both the SML and AML all fixation, the vibration of the stapes footplate was decreased obviously by 4 dB and 6 dB, respectively. By contrast, detachment of the SML and AML have little effect on the displacement of the stapes footplate. Conclusion:It is different that the effect of AML and SML on the vibration of the tympanic membrane and the stapes footplate. The SML fixation decreased the displacement of tympanic membrane and stapes footplate. Both the SML and SML all fixated decrease the stapes footplate significantly.But, there is little effect of the detachment of SML and AML on the displacement of the stapes footplate. PMID- 29798269 TI - [Autosomal dominant hearing loss resulting from mutation in the GJB2 gene:nonsyndromic presentation in a Chinese family]. AB - Objective:To investigate the genotype, phenotype and genetic features. The mutations in GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) were tested in a Chinese family with autosomal dominant nonsyndromic hearing loss. Method:Blood samples and clinical data of the proband and her partial family members were collected. DNA was extracted from the blood samples. The GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) mutations were analyzed by polymerase chain reaction(PCR) and direct sequencing. Result:Heterozygous mutation of GJB2 R75Q was identified in the proband and her mother. No mutation of other testing genes was detected. Conclusion:The R75Q mutation of the GJB2 gene cause autosomal dominant nonsyndromic deafness in the proband and her mother. Children can inherit the R75Q mutation from their parents, so the results of gene testing will be helpful for further guidance of procreation. PMID- 29798270 TI - [Association of RTN4 gene rs2864052 and rs6545468 with the susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang population]. AB - Objective:To study the relationship of the polymorphism of RTN4 gene rs2864052 and rs6545468 and haplotype with the susceptibility of nasopharyngeal carcinoma in Guangxi Zhuang population. Method:The polymorphism of Nogo gene (rs2864052,rs6545468) and haplotype were analyzed using the method of single-base extension PCR and DNA sequencing in 282 cases of nasopharyngeal carcinoma (NPC) and 199 healthy persons (control group) in Guangxi Zhuang Autonomous Region. Result:There were no differences between the NPC's patients and controls in the genotype and allele frequencies of RTN4 gene rs2864052 site,or rs6545468 site. The frequency of AG haplotype in the NPC's patients was significantly lower than in the controls(P=0.004, OR=0.14,95%CI=0.31-0.68). Conclusion:The haplotype AG of RTN4 gene rs2864052 and rs6545468 sites may reduce the risk of nasopharyngeal carcinoma in Guangxi Zhuang population. PMID- 29798271 TI - [Clinical and genetic investigation of families with Waardenburg syndrome type 2]. AB - Objective:To investigate the clinical chacteration and molecular pathology of Waardenburg syndrome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Method:Clinical data of seven families with WS2(14 patients)were collected. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of microphthalmia associated transcription factor (MITF), sex determining region Y-box 10(SOX10), snail family zinc finger 2 (SNAI2) and endothelin receptor type B(EDNRB)were analyzed by polymerase chain reaction and DNA sequencing. Then the raw data was analyzed. Result:The most common manifestations of WS2 are sensorineural hearing loss(10/14,71.4%), freckle(7/14, 50.0%),heterochromia iridis(6/14, 42.9%) and premature greying(5/14,35.7%). All the deafness phenotype is congenital, bilateral profound sensorineural hearing loss. Freckles phenotype is different from cutaneous pigment abnormalities of WS in Westerners. The heterozygous mutation, c.328C>T in exon 3 of the MITF gene was detected in the proband and all patients of pedigree 2. However, no pathological mutation of the relevant genes (SOX10,SNAI2 and EDNRB) was detected in other pedigrees. Conclusion:There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pigment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedigree WS02.However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research. PMID- 29798272 TI - [Efficacy and safety of conservative and nasal endoscopic therapy for residual nasopharyngeal carcinoma]. AB - Objective:To compare the efficacy and safety of conservative and nasal endoscopic therapy for residual nasopharyngeal carcinoma. Method:Eighty-two cases of residual nasopharyngeal carcinoma patients in our hospital were selected and according to the order of admission were equally divided into the nasal endoscopy group and the conservative group with 41 cases in each, the conservative group were given conservative treatment of radiotherapy and the nasal endoscopy group were given nasal endoscopic surgery, the effects , prognosis and complications were observed in the two groups. Result:The effective rates of nasal endoscopic group and conservative group were 92.7% and 75.6% after treatment for 6 moths, and the effective rate of nasal endoscopic group was significantly higher than that in conservative group (P<0.05). There were no serious complications such as massive hemorrhage of nose and throat and major organ damage in the two groups, and other complications were improved after symptomatic treatment. The overall survival, local recurrence free survival time and distant metastasis free survival time in the nasal endoscopic group were (34.24+/-2.19) months, (28.45+/ 1.98) months and (26.33+/-2.88) months, were significantly higher than those of the conservative group (26.46+/-1.98)months, (21.87+/-2.09) months and (20.44+/ 3.19) months(P<0.05). Conclusion:Compares with conservative radiotherapy, nasal endoscopic surgery in the treatment of residual nasopharyngeal carcinoma can improve the efficacy and safety, so as to prolong the survival time of patients that has good application values. PMID- 29798273 TI - [Surgical treatment and curative effect observation of vascular malformations in the adult floor of the mouth and pharyngeal space]. AB - Objective:To investigate the effect of surgical treatment of vascular malformation in the adult floor of the mouth and pharyngeal space. Method:Collect 12 cases of vascular malformation from the floor of the mouth and pharyngeal space.All of them were checked out of the different degrees of tongue elevation and dysphagia and to carry out the excision of vascular malformation with lingual nerve and hypoglossal nerve preservation. Result:The lesion reduction degree of 10 cases of patients were IV class(excellent), theoher 2 cases were III class(good). Hematoma at the bottom of the mouth after operation were not happened. Follow-up 0.5-3 years,tongue deviation appeared in 1 cases of postoperation. After 6 months of follow-up, the tongue is in the middle when it put out, functional recovery,no tongue muscle atrophy,no tongue movement disorder in the rest of the patients,no obvious recurrence of vascular malformations, no swallowing disorder in all patients. Conclusion:It would be obtained ideal therapeutic effect with surgical treatment in the adult vascular malformations of the floor of the mouth and pharyngeal space.It would be the key to the success of surgery with protecting the lingual nerve and hypoglossal nerve and controlling bleeding. PMID- 29798274 TI - [The surrounding radiation dose of iodine-125 seeds on normal larynx tissue in rabbits]. AB - Objective:To monitor the change of the radiation dose of the rabbits which were implanted rasioactive 125I seed into the normal laryngeal tiseue at different time,and to evaluate the safety of radiation protection. Method:Sixty New Zwaland rabbits, weighing 2.15-2.30 kg,were randomly divided into 5 groups:7 d,1month,2 month,4 month group and the control group, 12 rabbits in each group Iodine-125 of 0.8 mCi were implanted into the right side of the first trachea ring. At the different time and different distance, the surrounding radiation dose was measured after 4 months of implanting. The results were analyzed in statistics. Result:With the increase of the distance and the prolong of the time, the radiation dose was decreasing,and with the increase of distance,the radiation dose decreased slowly. At the site of 1 meter from the seeds, the detected dose is close to the natural background radiation dose. Conclusion:The clinical application of radioactive 125I seed interstitial implant is easy to protected,the surrounding close contacts is satety. PMID- 29798276 TI - [The values of LigaSure vessel sealing system in thyroidectomy for hyperthyroidism]. PMID- 29798275 TI - [Effect of Six1,TGF-beta,VEGF-C that promoting tumor lymphangiogenesis in human laryngeal carcinoma xenografts in nude mice]. AB - Objective:To research the effect of Six1,TGF-beta,VEGF-C that promoting tumor lymphangiogenesis in human laryngeal carcinoma xenografts in nude mice. Method:Technology of RNA interference was used for silencing Six1 and TGF-beta genes expression in laryngeal squamous cell, preparation Six1-targeting and TGF beta-targeting siRNA for transfecting into laryngeal squamous cell carcinoma, sieve out positive clone cell and amplify. Preparing bearing cancer mice, the mice were divided into five groups, group A (untransfected),group B(empty vector), group C(Six1-siRNA),group D(TGF-beta-siRNA),group E(Six1+TGF-beta siRNA). 6-12mm when the tumor has grown, the mice were sacrificed by cervical. The size of each tumor and metastasis were observed and recorded.The protein expression of Six1,TGF-beta and VEGF-C was determined by immunohistochemistry and Western blot.The mRNA of Six1,TGF-beta and VEGF-C was determined by RT-PCR. Result:The average tumor volume and the number of metastasis cases in group B have no statistically significant compared with group A. The average tumor volume in group C, group D and group E has no significantly reduced, but there is a clear reduction of the number of metastasis cases compared with group A. The average tumor volume and number of metastasis cases in group E has no significantly reduced compared with group C and group D. Both protein and mRNA expression of Six1, TGF-beta and VEGF-C in group B had no significant difference compared with group A. In group C, group D and group E,both protein and mRNA expression of VEGF-C was decreased,difference has statistically significant compared with group A. Both protein and mRNA expression of VEGF-C in group E had no significant difference compared with group C and group D. Conclusion:Both Six1 and TGF-beta can mediate tumor lymphangiogenesis and lymph node metastasis by mediate the expression of VEGF-C. Suggest that Six1,TGF-beta might be a potential therapeutic target for preventing lymph node metastasis of tumor. PMID- 29798277 TI - [Clinical observation on the modified surgical treatment of auricular pseudocyst on 31 cases]. PMID- 29798278 TI - [Application experiences of local flap in the resection of the children'sinfectious congenital preauricular fistula]. PMID- 29798279 TI - [Clinical analysis of plasma cell granuloma in nasal cavity and nasal sinus]. AB - The plasma cell granuloma occurred in nasal cavity and sinus, which is rarely seen in clinical practice,the common clinical features included nasal congestion,nose bleeding,eye protrusion and olfactory impairment.Its clinical manifestations are similar to the clinical manifestations of malignant tumors, the correct diagnosis depends on histopathology and immunohistochemistry, and surgical treatment is the main method, can be supplemented by hormone therapy, radiotherapy,the prognosis could be better. PMID- 29798280 TI - [Giant rhinolith: a case report]. AB - My department reports a case of giant rhinolith.Rhinolith is a rare and slow progressing disease. Clinically, rhinolith is easily to be misdiagnosed as sinusitis or sinus tumor. High-resolution computed tomography (HRCT) can be used to diagnose of rhinolith and differentiate it from sinusitis or sinus tumors. HRCT can also provide reliable evidence for evaluating surgery difficulty level and determining operation method. PMID- 29798281 TI - [Foreign bodies of external nose and forehead:a case report]. AB - Foreign bodies of external nose and forehead are rarely seen.In this case the patient stuck an acupuncture needle into the middle of two sides of the superliliary arch 3 months ago. Patient complains of slight pain in that region because of the infection.The X-ray and 3D CT examination present 4 abnormal high density shadows in the subscutaneous tissue of external nose and forehead.Foreign bodies in maxillofacial region have the quality of being changeable when the muscles are contracting. The key point to the successful operation is finding the accurate location of the foreign bodies with feasible image examination and designing reasonable incisions. PMID- 29798282 TI - [The relationship between lysosome-autophagy and the head and neck squamous cancer cell apoptosis]. AB - Autophagy can be used as both a protective mechanism of cell survival and a mechanism of cell death.The dual mechanism has been the emphases and difficulties of our research.The latest research shows that autophagy plays an important role in occurrence,development, transfer and treatment of the cancer.Head and neck cancer is usually derived from the upper respiratory tract's. The upper digestive tract's malignant tumor, because of its complex anatomic structure, low 5 years of survival rate, to study the prevention and treatment has the extremely important significance. The purpose of this paper is to clarify the role of lysosome-autophagy,mitochondria-autophagy in the treatment of head and neck cancers and the relationship between autophagy and apoptosis, which will be contribute to the prevention and treatment of head and neck squamous cell carcinomas for us.Autophagy as a cellular lysosomal degradation pathway that can be used as a kind of dynamic monitoring index of the tumor. PMID- 29798283 TI - [Progress in diagnosis and treatment of vocal fold nodules]. AB - Vocal fold nodules is the common cause of the hoarseness,which seriously affected people's living standard.At present,the treatment of the vocal fold nodules should be based on conservative treatment,surgical treatment as a supplement.Conservative treatment mainly includes:rest the voice,drug treatment,intervention and voice therapy.Surgical treatment is mainly the laryngomicrosurgery in suspension laryngoscope. The purpose of this study is to summarize the diagnosis and the treatment of vocal fold nodules,improving the reference of clinical workers. PMID- 29798284 TI - [Research status of vestibular migraine]. AB - Pathogenesis, clinical characteristics and treatments of vestibular migraine(VM) in recent years were retrospectively analyzed. The results showed that VM had diversified vestibular symptoms. VM may show a mild central and peripheral vestibular dysfunction during ictal and interictal period. Although no specificity, it could provide important references to identify VM. The pathogenesis of VM, which depended upon the clues of migraine, had been supposed to be probably related to genetic susceptibility, neurotransmitter changes induced by trigeminal nerve, and abnormal integration of central signal, and further exploration of functional abnormalities in brain-related areas showed by functional imaging technology may shed light on the pathogenesis of VM. Until now, the pharmacotherapies of VM have been still based on the treatment of migraine and the efficacy remains to be clarified. PMID- 29798285 TI - [Epidemiology, occupational and environmental risk factors of chronic rhinosinusitis in China]. PMID- 29798286 TI - [Mechanism of chronic rhinosinusitis with polyps and its association with high recurrence rate of polyps after sinus surgery]. PMID- 29798287 TI - [Surgical treatment of cronic rhinosinusitis with nasal polyps]. PMID- 29798288 TI - [Surgical treatment of difficult-to-treat chronic rhinosinusitis]. PMID- 29798289 TI - [The possible failing reasons of balloon catheter dilation procedure in the management of chronic rhinosinusitis]. AB - Objective:To investigate the effectiveness of balloon catheter dilation (BCD) in the treatment of chronic rhinosinusitis, and to analyse the possible factors which lead to BCD failure, as well as to provide basic reference for BCD clinical usage.Method:Forty-six sinuses of 32 patients with chronic rhinosinusitis were underwent "Balloon-only" BCD or "FESS assisted" BCD at our institution between September 2014 and December 2016. By recording details of the operation of all the subjects in this study and following up the clinical symptoms, nasal endoscopy, computed tomography of the sinuses, and postoperative complications six months after operation, to evaluate the difficulty, safety, effectiveness and especially, the failing reasons of BCD.Result:BCD was approached in 46 sinuses (19 maxillary sinus, 22 frontal and 5 sphenoid), and succeeded in 13 maxillary sinuses, 19 frontal sinuses, and 4 sphenoid sinuses. Of the 13 maxillary sinuses, there were 9 sinuses underwent "Balloon-only" procedure, other 4 cases underwent "FESS assisted" procedure. There were 3 cases of frontal sinus failed, because of the frontal recess anatomical complexity and the twisted drainage. Of the 5 sphenoid sinuses, 4 cases succeeded, including fungal sphenoiditis cases, in which the mould was completely cleared through the dilated ostia, and 1 case failed. All the patients were followed up for 1, 3 and 6 months of patient's quality of life, nasal endoscope, computed tomography of the sinuses. The results showed that the SNOT-20 scores of the quality of life in significant relief of symptoms, nasal mucosa status improved significantly compared with the preoperative, dilated ostium remains open, no obvious scar formation, no severe operative complications.Conclusion:Balloon catheter dilation in the treatment of chronic rhinosinusitis is safe and effective. But the operation indications is limited, and many factors influence the success rate of BCD, so, preoperatively gaining the information of nasal cavity and anatomical structure around ostium according to patients' nasal endoscopy and sinus CT is critical to success of BCD. PMID- 29798290 TI - [Diagnosis and treatment of basal cell adenoma of parotid gland]. AB - Objective:To investigate the clinical features, diagnosis and treatment experience of basal cell adenoma (BCA).Method:The clinical data of 7 patients with basal cell adenoma of the parotid gland from the Second Affiliated Hospital of Medical University of Anhui from March 2012 to June 2016 were retrospectively analyzed. Combined with literature review, the experience of diagnosis and treatment was discussed.Result:Seven BCA were mostly diagnosed as pleomorphic adenoma and adenomatous lymphoma before operation using parotid ultrasound, fine needle aspiration cytology and parotid enhanced CT, and no patients was diagnosed as BCA prior to the operation. Four cases were diagnosed as BCA, 1 case was diagnosed as adenoma, 1 case was diagnosed as low-grade malignant tumor, and 1 case was not able to identify benign or malignant tumor by intraoperative fast frozen pathological examination. There were no obvious complications after the operation, and only 2 cases of mild facial paralysis returned to normal in 1 month, and no recurrence was found in the follow-up 18-69 months. Conclusion:Basal cell adenoma of the parotid gland is a rare benign tumor of parotid gland, the lack of specific clinical manifestations and signs, preoperative ultrasonography, fine needle aspiration cytology and parotid gland enhanced CT scan can not confirm the diagnosis, although they have some limitations, they are of great value in the localization, qualitative and differential diagnosis of BCA in the parotid gland. The diagnosis mainly depends on intraoperative, postoperative pathology and immunohistochemical examination. The treatment is mainly surgical excision, and the prognosis is better. PMID- 29798291 TI - [The similarities and differences of mandarin open-set word recognition between cochlear implant children and normal hearing children]. AB - Objective:To evaluate the ability of open-set word recognition in cochlear implant (CI) children,and compare the similarities and difference of open-set word recognition between CI children and normal hearing(NH) children.Method:This study included 485 children with CI and 162 children with NH, who completed the Mandarin lexical neighborhood test. The results for children at 1-8 years after receiving their CI were compared to those from the children with NH using analysis of variance.Result:There were significant differences in open-set word recognition between the CI and NH groups(P<0.05).For implantation before 2 years, there was no significant difference in recognition at the ages of 6-7 years,compared to 3-year-old children with NH, or at the age of 10 years, compared to 6-year-old children with NH(P>0.05).For implantation before 3 years, there was no significant difference in recognition at the ages of 8-9 years, compared to 3-year-old children with NH,or at the age of 10 years, compared to 6 year-old children with NH(P>0.05).For implantation after 3 years, there was a significant difference in recognition at the age of 13 years,compared to 3-year old children with NH(P<0.05).Conclusion:Mandarin open-set word recognition increased with time after CI.Chinese children with CI had delayed but similar development of recognition, compared to normal children. Early CI can shorten the gap between children with CI and normal children. PMID- 29798292 TI - [Small interference of transcription factor Snail contribute to enhanced cisplatin sensitivity on human laryngeal resistant cancer cells]. AB - Objective:To study the relationship between transcription factor Snail and the sensitivity of cisplatin on human laryngeal resistant cancer cells.Method:siRNA interference of Snail was transfected by small RNA interference technology. The interference efficiency on mRNA level were detected by RT-qPCR assay; the expression of Snail protein level was assessed by immunofluorescence. The inhibition ratio of different cisplatin concentration (0, 1, 2, 4, 8, 16 MUg/ml) was detected by CCK-8 assay; the protein level of Snail, E-cadherin, MDR1were detected by Western blot assay.Result:RT-qPCR assay show the expression of Snail on mRNA level was decreased to (67.85+/-9.50)% after transfection in Hep-2/CDDP cell(P<0.05). Immunofluorescence show fluorescence intensity of si-Hep-2/CDDP group was reduced both in nucleus and cytoplasm; CCK-8 assay show the inhibitory ratio of transfected group was increased compared to negative control and Hep 2/CDDP group in different cisplatin concentration (0, 1, 2, 4, 8, 16 MUg/ml) (P<0.05). Western blot assay show the protein expression of Snail and MDR1 were down-regulated in transfected Hep-2/CDDP cells (allP<0.05), while epithelial marker E-cadherin was up-regulated in protein level (P<0.05).Conclusion:Small interference of transcription factor Snail could increase the expression of E cadherin while decrease the expression of MDR1, and it was confirmed that interference Snail contribute to enhanced cisplatin sensitivity on human laryngeal resistant cancer cells. PMID- 29798293 TI - [Experimental observation on the effect of bone marrow mesenchymal stem cells transplanting CXCR4 over gentamicin ototoxicity]. AB - Objective:To observe the survival and migration ability of CXCR4-BMSCs in guinea pig cochlea with gentamycin induced sensorineural hearing loss, and to explore whether SDF-1/CXCR4 axis can mediate bone marrow mesenchymal stem cells (BMSCs) to cochlear homing.Method:BMSCs were isolated and extracted from guinea pigs. A bone marrow mesenchymal stem cell line with overexpression of CXCR4 was established. The animal model of sensorineural deafness was established by intraperitoneal injection of gentamicin[100 mg/(kg.d)]in 50 healthy guinea pigs. The successful deafness animals were randomly divided into three groups(14 rats in each group): sterilizing water group, BMSCs transplantation group and CXCR4 BMSCs transplantation group.Auditory brainstem response(ABR) were performed at 2 weeks and 4 weeks respectively after the tansplantation through cochlear tympanic pathway. The directional homing of the implanted cells in the cochlea was traced by the frozen section fluorescence of the cochlear tissue.Result:The hearing thresholds of the three groups were (91.3+/-5.2),(90.7+/-4.8)and (90.9+/-5.6)dB (SPL) respectively. There was no significant difference among them(P>0.05). In sterile Water group, the hearing thresholds were(89.7+/-6.4)dB and (89.2+/-6.7)dB respectively when detected on 2 and 4 weeks after transplantation. There were no significant difference(P>0.05);In BMSCs group, the hearing thresholds were (88.6+/-5.3)dB(SPL) on 2 weeks and (78.4+/-7.3)dB(SPL) on 4 weeks after transplantation. In CXCR4-BMSCs group, the hearing thresholds were(75.3+/ 7.8)dB(SPL) on 2 weeks and (62.1+/-8.4)dB(SPL) on 4 weeks after transplantation. The differences were statistically significant (PThe hearing threshold was (75.3+/-7.8)dB (SPL) at 2 weeks after operation. The hearing enhancement was about 15 dB, the hearing threshold was (62.1+/-8.4)dB(SPL) at 4 weeks, the difference was statistically significant(P<0.05).Fluorescence tracing showed that the number of CXCR4-BMSCs homing cells was significantly increased, and showed a cohort like arrangement.Conclusion:The SDF-1/CXCR4 axis plays an important role in the directional homing and differentiation of the cells into the cochlea, which can improve the hearing repair ability of guinea pigs induced by gentamicin induced sensorineural deafness. PMID- 29798294 TI - [Preparation and comparative study of decellularized rat cricoarytenoid dorsalis muscle and gastrocnemius muscle scaffold]. AB - Objective:To prepare and to compare the decellularized rat cricoarytenoid dorsalis muscle and gastrocnemius muscle scaffolds for providing a basis for tissue engineered cricoarytenoid dorsalis muscle.Method:Sprague Dawley rats were randomly divided into 6 groups with 10 rats in each group.The experimental groups were divided as 2, 4, 6, 8, and 10day groups after decellularization. Muscles were decellularized with 1% sodium dodecyl sulfate and observed by general observation, histological section with hematoxylin eosin staining and collagenous fiber staining, scanning electron microscope images with measurement of pore diameter and area, and DNA extraction and quantification. The control group was not decellularized.Result:The decellularized muscles in experimental groups showed a semitransparent appearance while in control group the fresh muscle showed a ruddy color.Muscle fibers were completely disappeared in cricoarytenoid dorsalis muscle after 4 days decellularization and in gastrocnemius muscle after 8 days decellularzation, the extracellular matrix reserved well and no DNA was detected. Scanning electron microscope revealed a different pore size between decellularized cricoarytenoid dorsalis muscle and gastrocnemius muscle,and the difference was statistically significant. The pore diameter in 4 days decellularized cricoarytenoid dorsalis muscle was larger than the one in 8 days decellularzed gastrocnemius muscle.Conclusion:Compare to gastrocnemius muscle,decellularized cricoarytenoid dorsalis muscle has advantages in pore form and size and more suitable as a scaffold for tissue engineered cricoarytenoid dorsalis muscle. PMID- 29798295 TI - [Clinical investigation of basophil activation test as a complementary test for house dust mite allergen]. AB - Objective:To investigate the clinical application of glass micro fiber basophil activation test (BAT) used as a complementary test for house dust mite allergen.Method:Forty patients with clinical diagnosed allergic rhinitis was test by three methods for house dust mite allergen, skin prick test(SPT),Immuno CAP sIgE, and BAT in vitro. The sensitivity and specificity of glass micro fiber were accessed, and the consistency between BAT, SPT, and Immuno sIgE was analyzed. As in vivo provocation was not performed, gold standard is regarded as the combination of medical history and positive reports of SPT and/or ImmunoCAP sIgE test.Result:Twenty?three patients are diagnosed as house dust mite allergic rhinitis by gold standard. The sensitivity and specificity of glass micro fiber BAT were 60.9% and 88.2%, the sensitivity of SPT and sIgE was 87.0% and sIgE 73.9%. The correlation rates between BAT with SPT is 0.67(P<0.05), and sIgE 0.55(P<0.05). The accuracy, predictive value of positive and negative of BAT are 0.47,60.9%,88.2%.The Kappa values of BAT, SPT and sIgE with gold standard are 0.47,0.86,0.71.Conclusion:As a complementary test for house dust mite allergic rhinitis, BAT have a good consistency with SPT and sIgE, while as it has only moderate consistency with "gold standard", further studies are needed to prove its clinical significance. PMID- 29798296 TI - [Clinical observation of Weisu granules in treating laryngopharyngeal reflux]. AB - Objective:To observe the clinical effect of Weisu granules in treating laryngopharyngeal reflux.Method:One hundred and eighty patients were divided into three groups in random. Sixty patients in experimental group combined of Lanqin oral solution and Weisu granules. Sixty patients in control group A using Lanqin oral solution. Sixty patients in control group B using Esomeprazole Magnesium Enteric?coated Tablets and Lanqin oral solution. The treatment course ranges from 4 weeks.Result:Four weeks after treatment,clinical symptoms of all the three groups improved significantly. The effective curative rate in experimental group was 91.7% which better than that of the control group A 73.3%(P<0.05). After treatment, the symptoms and signs of the experimental group were significantly different from those in the control group A(P<0.05). There were no significant difference in the experimental group and the control group B(P>0.05).Conclusion:The therapeutic method of Weisu granules using in laryngopharyngeal reflux has obvious effects. PMID- 29798297 TI - [Efficacy analysis of T type tube dilatation in adult cervical tracheal stenosis]. AB - Objective:To investigate the efficacy, recurrence and strategy of T silicone tube dilatation for cicatricial stenosis of cervical trachea in adults.Method:Cinical data of 37 cases with the cervical tracheal stenosis were retrospectively analyzed, who were firstly treated by T shape silicone tube dilation for at least 10 months, from Jun 2006 to Jun 2016.Result:In 37 adult patients with cicatricial stenosis of the trachea, 29 cases were caused by tracheal intubation or incision, 6 cases were traumatic, and 2 cases were multiple osteochondritis. Twenty?three cases were experienced one time surgery and extubated successfully, 8 cases were experienced 2 times and more than 2 times surgery (sternohyoid muscle flap pedicled hyoid bone with T tube expansion in 3 cases, tracheal endoscopic dilatation in 2 cases, T tube dilatation in 3 cases), extubation success rate of 83.7%. Among the 6 cases with failure of extubation, 2 cases were multiple osteochondritis, 3 cases had severe scar constitution, 1 cases were lost of follow-up.Conclusion:T type silicon tube expansion for the treatment of adult cervical tracheal stenosis can be achieved relatively high decannulation rate. For recurrent stenosis, we can consider to use various methods of expansion, and improve the decannulation rate. Intratracheal granulation tissuextubation after exbation should be observed for at least 1 month. For concurrent with polychondritis and severe scar the constitution, the operation should be carefully chosen. PMID- 29798298 TI - [Longitudinal study of the early prelingual auditory development of children with cochlear implants]. AB - Objective:To explore the early prelingual auditory development (EPLAD) of children with cochlear implants.Method:Children with cochlear implants switched on at 1 and 2 years old in our center were recruited in this longitudinal study, and the EPLAD of them would be tested with the ITMAIS at 3months, 6months, and 12months after switch on. Each children could be permitted to miss follow-up one time.Result:Seventy-five children with unilateral cochlear implants were recruited in the study, and divided into 2 age groups according to the age at switch on,1 year group (32 children) and 2 years group (43 children). The EPLAD of children in both groups improved as the time they wore the cochlear implants increased. The speeds of improvement in both groups were similar to that of normal children and faster than those of children with different hearing impairments and without any interventions. The mean total score at 12 months after switch on in 1 year groups could achieve the average level of mild hearing impaired peer without interventions. In addition, the total scores in both groups were significantly different at 3 months after switch on(P<0.05),and no?significantly different at 6 and 12 months after switch on(P>0.05).Conclusion:Cochlear implant could help the children with profound sensorineural hearing loss to improve the abilities of EPLAD, and the speed of improvement in the 12 months after switch on was similar to that of normal children. And the results also indicated that the mean total scores at 12 months after switch on in both groups could be close to or achieve the average level of mild hearing impaired peer without interventions, it provided evidences to us for counseling and rehabilitation exercise. In addition, the result, total scores in both groups were just significantly different at 3 months after switch on, emphasized the importance of early intervention as well. PMID- 29798299 TI - [Etiology analysis and vestibular assessment of bilateral vestibular vestibulopathy]. AB - Objective:To define clinical and laboratory characteristics of bilateral vestibulopathy(BVP) and to propose diagnostic criteria of this disorder based on clinical and laboratory vestibular function test findings.Method:Forty-two case series with a clinical suspicion of BVP were retrospectively analyzed, in an attempt to determine etiology. Presenting auditory-vestibular symptoms, bedside dynamic visual acuity tests and laboratory test were reviewed, including bithermal caloric test, rotatory chair tests, video head impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP).Result:Among these 42 patients, dizziness was seen in 42 cases(100%), oscillopsia was seen in 21 cases(50%), hearing loss was seen in 30(71.4%). Eight cases(19%) had tinnitus. Twenty-five cases showed vestibular loss in dynamic visual acuity test (69.4%). Definite diagnosis of complete BVP was made in 36 patients when the patients showed abnormal findings on caloric test, rotatory chair test and vHIT in addition to the symptoms. Whereas probable diagnosis of partial BVP was obtained in 6 patients with abnormal caloric test and rotatory chair test but no pathological vHIT. VEMP (ocular or cervical) could be recorded in 20 patients. Fourteen cases were caused by ototoxic drugs while no causes could be determined in 6 cases among these 42 cases.Conclusion:The diagnosis of BVP is a challenge. Vestibular laboratory test battery which reflect full frequency function of VOR has great value to confirming the diagnosis and differentiate complete BVP to partial BVP. Diagnosis standard shall be made combining clinical history, characteristic symptoms and the results of auditory-vestibular function testing. Ototoxic drugs contribute most considering etiology. PMID- 29798301 TI - [Various nasal endoscopic approaches for treatment of maxillary sinus cyst]. PMID- 29798300 TI - [The efficacy comparation of adenoidectomy with acupuncture and tympanonstomy in children secretory otitis media]. AB - Objective:This study aims to the comparative study of AT+A (adenoidectomy with acupuncture) and AT+T (adenoidectomy with tympanonstomy tube) to monitor and compare the therapeutic effect and prognosis of secretory otitis media in children. The study make a summary and give the clinical suggestions as well.Method:We collected and analyzed 280 outpatients of children secretory otitis media from March 2015 to March 2016.Among them,172 cases took the adenoidectomy with acupuncture and 108 cases took the adenoidectomy with tympanonstomy tube. This research used the therapeutic effect indicators,middle ear effusion time and one year follow-up to evaluate the pros and cons of two surgery methods in different areas.Result:The patients of both groups had relatively good therapeutic effect which promoted with time. There were no significant difference between AT+A and AT+T in tympanic membrane. While AT+T group acted better than AT+A group in pure tone average and tympanum figure. The middle ear effusion time of AT+T group was significantly shorter than AT+A group. In one year follow-up, there were no difference in hearing loss between two groups.But AT+T group performed better in recurrence rate, infection rate and total rate.Conclusion:Since the adenoidectomy with tympanonstomy tube method has a lot of advantages over adenoidectomy with acupuncture,it's better to use AT+T in severechildren secretory otitis media when situation is available. PMID- 29798302 TI - [Diagnostic value of ultrasound-guided fine needle aspiration cytology of thyroid nodule]. PMID- 29798303 TI - [Cervical bronchogenic cyst in the superior mediastinum and literature analysis: a case report]. PMID- 29798304 TI - [Endoscopic middle ear surgery]. AB - Endoscopic transcannal middle ear surgery via natural route allows minimal surgery procedure which avoids incision of auricula and protects mastoid air cells. Utilizing endoscope of different angles provides excellent views of the "hidden corner" in middle ear, therefore helping surgeons better get rid of reduce residual pathological tissues. Surgeons in otology should understand middle ear anatomy and physiology as well as master the use of endoscopic surgical instruments to perform procedures well. treatment methods was present so as to further improve the understanding of such kind of tumor. PMID- 29798305 TI - [Clinical features and prognostic factors of squamous cell carcinoma of the base of tongue:an analysis of 124 cases]. AB - Objective:To summarize the clinicopathological characteristics and prognostic factors of squamous cell carcinoma (SCC) of the base of tongue (BOT). Method:Review the clinical data of 124 cases of patients with BOT tumors. HPV-DNA was detected using SPF10-DNA enzyme immunoassay and LiPA genotyping method. Survival rates and prognostic factors was calculated with SPSS 19.0 software using the Kaplan-Meier method and multivariate Cox model survival analysis. Result:5-year disease-specific survival (DSS), 5-year overall survival and median survival time for patients with SCC BOT were 54.5%, 48.5% and 45.2 months, respectively. HPV infection rate was 18.3%(11/60), the HPV-16 subtype in 10 cases, accounting for 90.9%(10/11). Univariate analysis results showed that smoking history (P=0.028), drinking history (P=0.001), tumor stage (P=0.009) and p16 protein expression (P=0.015) significantly affected the prognosis. The prognosis of patients with HPV positive BOT cancers was better than the HPV negative patients (5-year DSS was 80.8% compared to 54.5%), but not statistical difference (P=0.138). Multivariate analysis revealed that independent prognostic factors of BOT tumors were drinking history (P=0.006) and tumor stage (P=0.035). Conclusion:The prognosis of BOT tumor was relatively poor. Smoking history, drinking history, tumor staging and the expression of p16 protein significantly affected the prognosis. Drinking history and tumor stage were independent prognostic factors for BOT cancers. PMID- 29798306 TI - [Clinical characteristics and short term outcome of very old benign paroxysmal positional vertigo patients]. AB - Objective:To provide evidence and strategy for treatment of very old patients with benign paroxysmal positional vertigo (v-BPPV) by retrospective analysis of v BPPV patients. Method:According to the criteria, 19 v-BPPV patients were collected, aging from 80 to 91 years old, including 10 horizontal semicircular canal BPPV (HC-BPPV), 4 posterior semicircular canal (PC-BPPV) and 5 mutiple semicircular canal BPPV patients. PC-BPPV patients were treated by Epley or Li maneuver, and HC-BPPV patients were treated by Barbecue or Li maneuver. Each patient was treated twice, with an interval of 5 to 10 minutes. Result:Rates of 3 day cure and efficacy were 63.16% and 94.74%, respectively. Rates of 1-week cure and efficacy were 89.47% and 100.00%, respectively. Conclusion:v-BPPV can have good outcomes via proper treatment. Age should not influence BPPV outcomes, while we should pay more attention to v-BPPV patients' physiclal status and systematic diseases which may increase risk to diagnosis and treatment. PMID- 29798307 TI - [Application of digital 3D imaging technique in flap design before maxillofacial soft tissue reconstruction]. AB - Objective:Using digital technique to design the preoperative flap of oral and maxillofacial soft tissue defect, to instruct the operation and to provide the basis for making the individual femoral flap. Method:We chosed 7 patients with oral and maxillofacial malignancies to undergo thin-line CT scans of lower extremities and analyzed the data of CTA examination to measure the diameter, shape and length of vascular pedicle. Then selected the appropriate perforation as the source of blood supply for flap. The location of perforation was marked on the skin to simulate flap removal range.During the surgery according to the preoperative mark, draw lines and mark flap size. After flap preparation is completed, suture the donor area directly and build in negative pressure drainage tube. Result:All reconstruction of the anterolateral femoral artery descending perforator flap can show the skin, muscle, blood vessels and their adjacent relationship, and according to the size of the defect area, using Mimics 17.0 software simulation to cut flap which should be the same as the defect area. The main perforating branches and trunks of seven skin flaps were consistent with pre operative examination and all skin flaps survived; the wound surface and the donor were all in stage I healing. After operation, patients were followed up for 1-6 months and the form, quality and function of skin flaps all recovered well. Conclusion:The location of lateral femoral circumflex artery descending limb and perforating branch were accurately located by digital technique three-dimensional reconstruction technology, showing the spatial relationship among skin, muscle, blood vessels and bones. By combining with Mimics 17.0 software, it can achieve three-dimensional and accurate design of anterolateral thigh flap, reduce the donor injury and improve the successful rate of skin flap. PMID- 29798308 TI - [The predictive value of parathyroid hormone levels and decreases for postoperative hypocalcemia after total thyroidectomy]. AB - Objective:To investigate the predictive value of parathyroid hormone levels and decreases for postoperative hypocalcemia after total thyroidectomy. Method:We reviewed 71 consecutive patients who underwent total thyroidectomy, measured postoperative hypocalcemia, parathyroid hormone (PTH) values within 24 hours after surgery, divided them into subgroups accroding to hypocalcemia symptom. Combining with postoperative serum calcium,postoperative PTH values and decreases (?PTH), we used the receiver operating characteristic curve (ROC) analysis to assessment of predictive value. Result:The mean value of postoperative serum calcium, postoperative PTH and ?PTH between subgroups have a significant difference (P<0.01). ROC area under the curve (AUC) of ?PTH is 0.9706, with cutoff value 0.7366. AUC of postoperative PTH is 0.9580, with cutoff value 14.82 ng/L. Conclusion:The postoperative PTH and ?PTH is a reliable indicator to judging postoperative hypocalcemia after total thyroidectomy. PMID- 29798309 TI - [The clinical features and prognosis of nasal Schwannoma]. AB - Objective:To investigate the experience of nasal Schwannoma in order to provide guidance for the diagnosis and treatment of the disease. Method:Clinicopathological data and follow-up results of nine patients, which histopathology proved nasal Schwannoma were collected and analyzed. Result:The patients were referred to our clinic due to the space-occupying symptoms or signs of tumour compression. There were no specific findings in imaging examination. The patients were treated by operation except a multiple Schwannoma patient.The recurrence after operation were rare. The main features of pathological diagnosis was a strong expression of S-100 protein. Conclusion:Nasal Schwannoma usually has no specific clinical manifestations. Imaging examination is valuable to the determination of surgical range and the diagnosis of benign and malignant diseases. The diagnosis depends on histologic examination. Surgery is the only effective treatment. The best surgical procedure selection hinges on the lesion location and the prognosis is excellent. PMID- 29798310 TI - [Applied anatomy of the cerebelloponotine angle through retrosigmoid approach]. AB - Objective:To privde anatomical basis for the surgical operation of endoscope assisted retrosigmoid approach. Method:In 20 adult head cadavers fixed with formalin (40 sides), the surgery via retrosigmoid approach was simulated. The anatomic features of the cerebellopontine angle were examined and measured. Result:The distance from the midpoint of posterior border of sigmoid sinus to acoustic nerve near internal acoustic pore, trigeminal nerve near Meckel's cave, glossopharyngeal nerve near jugular foramen and the posterior margin of internal acoustic meatus were (32.8+/-1.7)mm, (46.3+/-1.8)mm, (29.4+/-3.0)mm, (31.2+/ 2.0)mm. The tracks of degree of angle of median sagittal plane were (32.6+/-7.7) degrees , (31.4+/-4.1) degrees , (40.2+/-6.9) degrees , (32.7+/-4.9) degrees . Conclusion:The measurement provides some useful references for defining the position in operating. PMID- 29798311 TI - [The comparison of clinical features and laboratory indexes between flat descending hearing loss and total hearing loss]. AB - Objective:To discuss similarities and differences in clinical features and laboratory indexes between patients with flat descending type sudden hearing loss and those with total hearing loss. Method:The clinical data of 123 patients with full frequencies hearing loss were retrospectively analyzed. The differences in clinical features and laboratory tests(platelet, coagulation series, D-dimer, blood lipids, hemorheology) between patients with flat descending hearing loss and those with total hearing loss were analyzed by gender, age and ear side, treatment time, concomitant symptom (tinnitus, dizziness), original underlying diseases (hypertension, diabetes), etc. Result:In the clinical features,among 51 flat descending cases, the ratio of male and female was 2.401:1; among 72 total hearing loss cases, the ratio of men and women ratio was 1.058:1 (P<0.05). Among two groups of patients,the majority received treatment within 7 days, among whom 66.7% were flat descending population, and 83.3% were total hearing loss population (P<0.05). Flat descending population with dizziness only accounted for 35.3% while this figure was up to 70.8% when it came to total hearing loss patients (P<0.01). Two groups showed no differences in age, ear side, tinnitus, the original underlying diseases (hypertension, diabetes). In the laboratory tests, the total hearing loss population overtopped the plat descending population in PLT and PCT (P<0.05), while falling below the plat descending population in APTT (P<0.01). Two groups showed no differences in other indicators of platelet and coagulation series and laboratory data of D-dimer, blood lipids, hemorheology. Conclusion:Compared with flat descending sudden hearing loss, sudden total hearing loss more frequently happened to females who also were accompanied by dizziness. The treatment rate within 7 days was high and the patients with hypercoagulable state accounted for a higher proportion. PMID- 29798312 TI - [Efficacy and safety of endonasal phototherapy in the treatment of adult allergic rhinitis: A Meta-analysis]. AB - Objective:To perform a systematic review of the efficacy and safety of endonasal phototherapy in the treatment of AR, and to provide evidence of evidence-based medicine for clinical application. Method:Databases were from PubMed, Embase, Cochrane Library, Chinese Academic Journal Full-text Database (CNKI) and Wanfang database. A randomized controlled trial (RCT) or clinical study literature on intranasal phototherapy for adult AR is available, and the deadline is March 2017. Based on the literature inclusion and exclusion criteria, the related literatures were selected and the quality was evaluated by using the Cochrane inclusion bias assessment table. Meta-analysis was performed with Revman 5.3 software. For continuous outcomes, the weighted mean difference (WMD) and its 95% confidence intervals (CI) were calculated, forest maps and funnel plots were drew. For uncontinuous outcomes, the odds ratio (OR) and its 95%CI were calculated, and forest maps and funnel plots were drew. The efficacy included total nasal symptom scores (TNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and palate itching scores, and the safety was assessed by incidence rate of severe drying and mild drying of nasal mucosa. Result:A total of 12 articles were selected, including 5 RCT and 7 clinical studies, and there were 615 adult AR patients. The Meta-analysis shows that endonasal phototherapy significantly reduced the TNSS, RQLQ and palate itching scores, the incidence rate of mild drying of nasal mucosa was higher in comparison with pretreated values, and the difference was statistically significant (P<0.05). The rate of severe drying of nasal mucosa was higher, but the difference was not statistically significant (P>0.05). It also shows that endonasal phototherapy significantly reduced the TNSS, RQLQ and palate itching scores, and the rate of mild drying of nasal mucosa was higher in comparison with placebo and antihistamines groups, and the difference was statistically significant. The rate of severe drying of nasal mucosa was higher, but the difference was not statistically significant. Conclusion:Endonasal phototherapy can improve the symptoms of TNSS, RQLQ and palate itching score in patients, and the safety is also confirmed.Patients who are not satisfied with symptom relief may choose to use it. PMID- 29798313 TI - [A study on P16 and HPV16 in sinonasal squamous cell carcinoma]. AB - Objective:The aim of this study is to evaluate the relationship between the expression of P16 and infection of HPV16 in sinonasal squamous cell carcinoma and its clinical and pathological features, futher prognosis was also investigated. Method:Fifty-five cases of sinonasal squamous cell carcinoma were collected,twenty cases of nasal in-verted papilloma and twenty cases of nasal polyp were chose as control. The expression of P16 and infection of HPV16 were detected by immunohistochemistry in both experimental group and control group. Result:The positive rate of P16 and HPV16 in sinonasal squamous cell carcinoma and nasal in-verted papilloma were significantly higher than it in nasal polyp (P<0.05 or P<0.01). The expression of P16 was correlated with tumor differentiation and clinical TNM stages (P<0.05), but was not associated with age, sex, smoking and the primary tumor site (P>0.05). HPV16 infection has no statistical relationship with analysis factors (P>0.05). There was a positive correlation between P16 expression an HPV16 infection in the cases of sinonasal squamous cell carcinoma (r=0.483, P<0.01). Survival curves showed that the expression of P16 and infection of HPV16 were positively associated with prognosis of sinonasal squamous cell carcinoma, Log Rank test showed a significant difference (P<0.05). Conclusion:The abnormal expression of P16 and HPV16 infection play an important role in the development of sinonasal squamous cell carcinoma. The two may had a synergistic effect. P16/HPV16 positive cases had better prognosis. PMID- 29798314 TI - [The correlation between normal or abnormal vestibule function and prognosis of the low frequency sudden deafness]. AB - Objective:To study the correlation between prognosis and status of the vestibule functions with the patients of the low frequency sudden deafness (SD). Method:Eighty-eight patients with low frequency SD were enrolled in this study, the cervical vestibular evoked myogenic potential (cVEMP), the ocular VEMP (oVEMP) and caloric test were evaluated. Based upon the results of the test, patients were divided into 4 groups. A group has no abnormal test results, B group has one abnormal test results, C group has two abnormal test results,and D group has three abnormal test results. Calculating and comparing the effective rate and uneffective rate were conducted in every group after treatment. Result:In A group, the effective rate is 27.27%, the uneffective rate is 2.27%. In B group, the effective rate is 36.36%, the uneffective rate is 4.55%.In C group, the effective rate is 9.09%, the uneffective rate is 6.82%. In D group, the effective rate is 0%, the uneffective rate is 13.64%. The difference between effective and uneffective rate was significant in group A, B, and D, while, there was no significant difference in group C. Conclusion:The prognosis of low frenquency SD patients without abnormal test results or only with one abnormal test results is good. While, the prognosis of patients with three abnormal test is bad. The prognosis of patients with two abnormal test is not sure. The vestibule functions test can be used to determine the prognosis of low frequency SD in clinical treatment. PMID- 29798315 TI - [Effect of CCR3 gene knockout on eosinophils in mice]. AB - Objective:To investigate the effect of CCR3 gene knockout on the proliferation, maturation and apoptosis of eosinophils (EOS) in mice. Method:Bone marrow cells from CCR3 gene knockout mice (experimental group) and wild-type mice (control group) were cultured in vitro and induced differentiation into mature EOS. EOS proliferation was observed by cell counting.Expression of degranulation protein mRNA was detected by qRT-PCR. EOS apoptosis was detected by Annexin V-FITC/PI double staining method. Result:1The number of cells on the 0-14 day of EOS cultured in vitro showed that the number of cells in the experimental group was less than that in the control group at tenth, twelfth, fourteenth days, and the proliferation was slower, the difference was statistically significant (P<0.01). 2The test results of EOS cells apoptosis showed that, under the condition of containing 10 ng/ml IL-5 or no IL-5, the apoptosis rate of EOS cells in experimental group was higher than that in normal control group, the difference between both groups was statistically significant (P<0.01). 3The expression results of ECP, EPO, MBP mRNA in EOS showed that the expression levels of ECP, EPO, MBP mRNA in the experimental group compared with the normal control group were reduced in varying degrees, the difference between both groups was statistically significant (P<0.05). Conclusion:Knockout CCR3 gene can inhibit the proliferation and maturation of EOS and promote its apoptosis, which provides a theoretical basis for CCR3 as a target gene to treat allergic rhinitis. PMID- 29798316 TI - [Clinical research of anxiety and depression state among patients suffered from sudden deafness with vertigo]. AB - Objective:To offer the objective evidences for the diagnosis by analyzing anxiety and depression among patients with sudden deafness and vertigo and their possible causes. Method:Eighty patients with sudden deafness and vertigo of single ear as the observation group; 80 patients with sudden deafness without vertigo and 60 healthy people as control group.Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD) are used for quantitative analysis and compare the results of each group score. Result:1The HAMA score of the deafness group with vertigo was significantly higher than that of the group without vertigo and the healthy group (P<0.01). The HAMD score of the deafness group with vertigo was significantly higher than that of the group without vertigo and the healthy group (P<0.01). 2There was correlation between HAMA and sex, age, duration of dizziness, tinnitus, DHI and efficacy grading (P<0.05). There was no correlation between HAMA and the mean hearing threshold, urban and rural distribution, ear fullness (P> 0.05). There was a correlation between HAMD and sex, age, tinnitus, DHI and efficacy grading (P<0.05). There was no correlation between HAMD and the mean hearing threshold, duration of dizziness, urban and rural distribution, ear fullness (P>0.05). Conclusion:There are anxiety and depression in patients with deafness and vertigo. It is mainly related to sex, age, dizziness duration, tinnitus, DHI and grade of efficacy. It is necessary to pay attention to the mental state of patients in clinical treatment. Psychological counseling or treatment can be used to improve clinical efficacy. PMID- 29798317 TI - [Clinical analysis of 5 invasive fungal rhinosinusitis cases]. AB - Objective:To discuss the clinical characteristics, treatment and prognosis of invasive fungal rhinosinusitis (IFRS). Method:Among the five patients who were diagnosed as IFRS, 4 patients had history of diabetes mellitus, and 1 case had a history of leukemia and chemotherapy. All the patients were treated through operation and antifungal therapy. Result:The patients were followed 1 year to 3 years after the operation. And 3 patients were clinical cured, 1 was died because of relapse, and 1 was died because of exacerbation. Conclusion:The diagnosis and treatment of IFRS need to be considered through many aspects. Antifungal therapy and medical treatment based on surgery might improve the recovery rate. PMID- 29798318 TI - [Analysis of the recurrence related factors of sinonasal inverted papilloma]. AB - Objective:To evaluate the influence risk factors of recurrence and the methods for reducing recurrence of sinonasal inverted papilloma (SNIP). Method:Clinical data of 34 patients with SNIP were analyzed retrospectively. All of them were unilateral onset. The diagnosis was confirmed pathologically and the range of lesions was determined by endoscopic and imaging examination; clinical classification according to Krouse classification method; All operations were performed under nasal endoscope, of which 20 cases were operated by simple nasal endoscope, and 14 cases were operated by endoscopic anterior lacrimal recess approach. The patients were followed up for 12-36 months. The curative effects were observed and the prognostic factors of the patients were analyzed. Result:Thirty-four cases of SNIP patients with postoperative recurrence rate was 17.65% (6/34); simple nasal endoscopic surgery in 20 cases, the recurrence rate was 25.00%(5/20); endoscopic anterior lacrimal recess approach in 14 cases, the recurrence rate was 7.14%(1/14), the difference was statistically insignificant (chi2=1.807, P>0.05). Four cases in stage I had no recurrence;20 cases in stage II, the recurrence rate was 15.0%(3/20); 9 cases in stage III, the recurrence rate was 33.3%(3/9); 1 case in stage IV had no recurrence, the recurrence rate of the patients with different stages were statistically insignificant (chi2=2.692, P>0.05).? Conclusion:Simple endoscopic resection of the tumor and endoscopic anterior lacrimal recess surgery are effective methods for the treatment of SNIP. The nasal surgery history and tumor origin are the risk factors for recurrence. The operation completely tumorresection,detailed preoperative examination and postoperative regular endoscopic examination are the keys to preventing recurrence. PMID- 29798319 TI - [Treatment of recurrent chylous leakage after neck dissection for one case with thyroid carcinoma]. AB - The incidence of chylous leakage which is one of serious complications after neck dissection is low. The recurrent chylous leakage is even rare. One patient with recurrent chylous leakage after the operation of thyroid papillary carcinoma is reported to investigate the pathogenesis and effective treatment of recurrent chylous leakage after neck surgery. PMID- 29798320 TI - [Removal of a giant ethmoidal sinus osteoma with orbital extension]. AB - Osteomas are slow growing bony tumors of the nasal sinuses. Ethmoid osteomas with orbital extension are unusual. Any surgical approach has to take into account protection of the vital structures, particularly the optic nerve and internal rectus muscle, skull base. A 65-year-old man, without past medical history, was referred to our hospital with a 1-month history of double vision and persisting pain around the left eye. Three-dimensional computed tomography (CT) revealed a large calcified dense mass measuring 32 mm * 25 mm * 25 mm in the left ethmoidal sinus with orbital extension. An endoscopic endonasal approach combined with inner canthus way was planned. Most of the tumor was removed from nasal cavity, the rest part of the tumor was taken out of the inner canthus incision. The medial wall of the orbital cavity was repaired with titanium mesh. No cerebrospinal fluid (CSF) leakage was observed during the procedure. The patient recovered rapidly and had no visual impairment and occular motility disorders after operation. The double vision was alleviated and disappeared after one months. Treatment of large ethmoid osteomas requires a combined approach to prevent injury to the orbital content. The cooperation of both otolaryngologists and ophthalmologists is necessary to achieve risk-free surgery. PMID- 29798321 TI - [One case of multiple primary carcinoma: laryngeal neuroendocrine carcinoma complicated with splenic mantle cell lymphoma]. AB - To report a rare case of multiple primary carcinoma:laryngeal neuroendocrine carcinoma complicated with splenic mantle cell lymphoma to improve the understanding of multiple primary carcinoma. The incidence rate of multiple primary carcinoma was low. Laryngeal neuroendocrine carcinoma with mantle cell lymphoma has not been reported yet. Early diagnosis and antidiastole is very important for MPC. Pathological examination and immunohistochemistry plays an important role in the diagnosis of multiple primary carcinoma, laryngeal neuroendocrine carcinoma and mantle cell lymphoma. PMID- 29798322 TI - [Bilateral vestibulopathy]. AB - The leading symptoms of bilateral vestibulopathy (BVP) are postural imbalance and unsteadiness of gait, deficits of spatial memory and navigation. The etiology of BVP remains unclear in more than 50% of patients: in these cases neurodegeneration is assumed. Frequent known causes are ototoxicity mainly due to gentamicin, bilateral Meniere's disease, autoimmune diseases, meningitis and bilateral vestibular schwannoma, as well as an association with cerebellar degeneration. The diagnosis of BVP is based on a bilaterally reduced or absent function of the vestibulo-ocular reflex (VOR). Head impulse test (HIT), video oculography system (vHIT), crvical/ocular vestibular-evoked myogenic potentials (c/oVEMP) and dynamic visual acuity is an additional test supporting the diagnosis. There are four different subtypes of BVP depending on the affected anatomic structure and frequency range of the VOR deficit: impaired canal function in the low-and/or high-frequency VOR range only and/or otolith function only; the latter is very rare. There are four treatment options: first, detailed patient counseling to explain the cause, etiology, and consequences, as well as the course of the disease; second, daily vestibular exercises and balance training; third, if possible, treatment of the underlying cause, as in bilateral Meniere's disease, meningitis, or autoimmune diseases; fourth, if possible, prevention, i.e., being very restrictive with the use of ototoxic substances, such as aminoglycosides. PMID- 29798323 TI - [A review on group 2 innate lymphoid cells and miR-155 in allergic rhinitis]. AB - Allergic rhinitis (AR) is the Th2 inflammatory response that atopic individuals exposure to allergens, mediators released by IgE-mediated, and a variety of immunocompetent cells and cytokines involved .Group 2 innate lymphoid cells (ILC2) are a novel population of native lymphocyte, can secrete large amounts of Th2 cytokines to promote the development of allergic diseases after being activated. MiR-155 plays a vital role in the development of the immune system, the differentiation of immune cells, and the maintenance of immune function.Nasal mucosas from the patients with allergic rhinitis show enrichment for ILC2 and miR 155. Highly expressed miR-155 may enhance the level of IL-4 by promoting ILC2 expression, thereby promoting Th2 inflammatory response.This review focuses on the function and meaning of ILC2 and miR-155 in patients with Allergic rhinitis. PMID- 29798324 TI - [Variation trend and significance of adult tonsil size and tongue position]. AB - Objective:The aim of this study is to explore the changing trend and significance of adult tonsil size and tongue position by observing adults in different age groups. Method:Oropharyngeal cavities of 1 060 adults who undergoing health examination and had no history of tonsil surgery were observed. Friedman tongue position (FTP) and tonsil size (TS) were scored according to Friedman's criteria and results were statistic analyzed to evaluate their changing law and significance. Result: Mean FTP scores increased with age significantly(P <0.01); FTP score in male was lower than that in female(P <0.01). TS score significantly decreased with age(P <0.05).The average score of TS had no statistical significance in different gender. Although there was no statistical significance, total score of FTP show an increasing trend with age(P >0.05);Total scores of FTP were different between sexes(male 4.12+/-0.67,female 4.23+/-0.68,P <0.05).BMI was not found to be statistically different when FTP scores, TS scores and total scores changed (P >0.05); but it showed an increasing trend with age(P <0.01). Conclusion:Width of pharyngeal cavity in normal adults is always kept in certain stability, while it proves to be narrower in obese people. TS score and FTP score, which appear the opposite trend with age, can be thought as a major factor to keep a stable width of oral pharyngeal cavity. PMID- 29798325 TI - [The phase II clinical trial of Yanhouqing buccal tablets in the treatment of acute pharyngitis of external wind heat type]. AB - Objective:The aim of this study is to preliminary evaluate the clinical efficacy and safety of Yanhouqing buccal tablets in the treatment of acute pharyngitis of external wind heat type and explore the safe and effective dose. Method:Design of multi-center clinical trial with randomized, double-blind, single-analog, placebo controlled, dose exploration. 288 patients were divided into three groups: low dose group, high dose group and placebo group. The effectiveness evaluation indexes was analysis of pharyngalgia or odynophagia, throat burning, TCM syndrome and pharyngeal signs, and the safety was evaluated by vital sign, lab examination indexes and adverse events. Result:The results showed that there was the statistically significant difference between high/low dose group and placebo group(P <0.01), and no significant difference between high and low dose groups(P >0.01) among the effectiveness evaluation indexes. There were no serious adverse events. The adverse events and adverse reactions in the three groups has no statistical significance(P >0.05). Conclusion:Yanhouqing buccal tablets is safe and effective in the treatment of acute pharyngitis of external wind heat type. We recommend 8 tablets per day and treat for 5 days in phase III clinical trials. PMID- 29798326 TI - [Clinical and pathological analysis of 1116 cases of vocal cord polyp]. AB - Objective:The aim of this study is to investigate the clinical and pathological features of vocal cord polyp. Method:Retrospective analyzed the clinical and pathological data of 1116 cases in vocal cord polyp patients treated with suspension microlaryngoscopic surgery. Result:The bradycardia was observed in 170 cases(15.2%) during the suspension of laryngoscope under general anesthesia. In this case,the suspension was stopped or the laryngoscope was taken out of mouth and atropine was administrated by intravenous injection. After that, heartbeat gradually accelerated and approached to normal,then the suspension was begun again to complete microlaryngoscopic surgery. Among the 1116 cases,1094(98%) were cured,22(2%) were improved,and no case was invalid. No pharyngeal injury was in 865 cases(77.5%). Mild,moderate and severe palatoglossal arch injury was observed in 139 (12.5%)cases,86(7.7%)cases,and 26 (2.3%) cases,respectively. The incidences of epithelial hyperplasia and dysplasia in vocal cord polyp were 35.3% and 5.0%, respectively. The prevalence rates of epithelial hyperplasia and dysplasia in male and female patients of vocal cord polyp were 76.2%,23.8% (P <0.01) and 78.6%,21.4% (P <0.01),respectively. And the prevalence rates of keratinization and parakeratosis in male and female patients were 93.1%,6.9% (P <0.01) and 93.1%,6.9% (P <0.01),respectively.The incidence of keratinization in patients of no epithelial hyperplasia, epithelial hyperplasia and epithelial dysplasia were 2.1%,18.2% and 30.3%,respectively,with significant difference in pairwise comparison.Conclusion:High incidence of vocal cord polyp is at the age from 31 to 60 years old.Although laryngomicrosurgery is an effective treatment for vocal cord polyp, pharyngeal injury and laryngopharyngeal vagal reflex should be noticed during the operation.In addition,vocal cord polyps in male patients are susceptible to epithelial dysplasia and keratinization. PMID- 29798327 TI - [Effects of HPA and NF-E2 related factor on smoking related laryngeal squamous cell carcinoma]. AB - Objective:To further explore the prognostic effects of Heparanase(HPA) and NF-E2 related factor (NRF2) on smoking related laryngeal squamous cell carcinoma,we detect the expression of HPA and NRF2 on smoking related laryngeal squamous cell carcinoma patients.Method:Continuously collected 84 patients with laryngeal squamous cell carcinoma in the Ningde Hospital from 2014 to 2015.All patients were divided into three groups according to smoking index:group A (severe smoking patients with laryngeal carcinoma 30 cases),group B(mild to moderate smokers 20 cases) and group C (no smoking in laryngeal carcinoma patients with 34 cases).Antioxidative indices in serum and the expression of HPA and NRF2 in three groups of patients were detected, and to explore their relationship with prognosis and clinical staging of patients.Result:The HPA and NRF2 were highly expressed in the cancer tissues of patients with stage III-IV,while the expression of HPA and NRF2 in patients with stage I-II was low. The expression level of NRF2 in group A was significantly higher than that of group Band group C(P <0.05) as well as the NRF2 expression levels in higher stage patients with laryngeal cancer were higher than those of low stages.The expression of HPA and NRF2 is related to the pathological stage in laryngeal squamous cell carcinoma patients(P <0.05).Conclusion:Compared with non smoking patients, severe smoking patients with laryngeal cancer will face more severe oxidative stress. The expression of HPA and NRF2 in laryngeal squamous cell carcinoma patients is related to the pathological stage. PMID- 29798328 TI - [The analysis of the misdiagnosis big data of the otolaryngology during 2004 to 2013 in China]. AB - Objective:The aim of this study is to explore the misdiagnosis status of the otolaryngology in China as well as to provide evidence to reduce misdiagnosis and improve the diagnostic level.Method:The retrieval and management system of the misdiagnosed diseases database developed by Chen Xiaohong was used for searching the literature of the misdiagnosis in otolaryngology.The 10 year' smisdiagnosis literature data of the otolaryngology(from 2004 to 2013) were analyzed including the literature sources, sample size, misdiagnosis rate,misdiagnosis consequences and misdiagnosis reasons.Result:A total of 369 articles were found,including 4211 cases.The average misdiagnosis rate was 25.43% in 51 diagnosed diseases.The top misdiagnosed diseases were nasopharyngeal tuberculosis(84.76%),tuberculous otitis media (75%) and congenital laryngeal cyst(75%).The lowest misdiagnosed disease was nasosinusitis(5.92%).The top three misdiagnosed diseases were tuberculosis of otolaryngology(1216 cases),nasosinusitis(710 cases) and BPPV(697 cases).After statistical analysis,we found that 97.22% of the misdiagnosed patients were grade III consequences (that is the misdiagnosis and mistreatment does not cause adverse consequences),but there were still 10 cases caused gradeIconsequences(death or sequela).The main causes of the misdiagnosis were lack of diagnosis experience, non detailed interrogation and physical examination and non targeted examinations.Conclusion:The big data of the 10 years reflects the misdiagnosis phenomenon in otolaryngology to some extent.Neurologist, stomatologist and ophthalmologist should be familiar to the main points of the differential diagnosis diseases of the otolaryngology and strive to reduce the clinical misdiagnosis and mistreatment. PMID- 29798329 TI - [Clinical characteristics and surgical management in patients with third and fourth branchial anomalies]. AB - Objective:To analysize the clinical characteristics as well as the effect and methods of the surgical treatment in patiets with the third and fourth branchial anomalies.Method:The clinical data of 25 patients diagnosed as third and fourth branchial cleft fistula by pathological method were analyzed retrospectively.Two of 25 patients had undergone fistulectomy simply.Based on the embryologicc and anatomic features of branchial anomalies,23 of 25 patients had received different types of selective neck dissection.All of lesions were confirmed as branchial cleft fistula by pathology.All patients were received the examinations of Esophagus myelography,MRI and CT preoperatively.Result:The features of the third and the fourth bianchial fistula were as following:most patients suffered from recurrent neck abscess and had undergone incision and drainage. Esophagus myelography and CT were important auxiliary examination for branchial anomalies.No recurrent and complications were found in all patients by using treatment of selective neck dissection (23/25 cases) and fistulectomy simply(2/25 cases) within 12 to 36 months following-up,postoperatively.Conclusion:Branchial anomalies is characterized by recurrent acute abscess,acute thyroiditis or fistula secretion inferior to neck.Complete removal of branchial lesions and inflammatory granuloma using selective neck dissection is a safty and effective treatment for recurrent branchial anomalies. PMID- 29798330 TI - [Relationship between full flowering stages of anemophilous and ligneous plants and consultation rate of allergic rhinitis]. AB - Objective:The aim of this study is to investigate the climatic changes on spring phenology impacting on the consultation rate of patients with allergic rhinitis.Method:We analyzed the periods of full flowering stages of 15 kinds of flowers in Beijing from 2013 to 2014,and the number of patients with allergic rhinitis in the outpatient clinic of Otolaryngology Department of Peking University Third Hospital in the same time.The correlation test, analysis of variance and rank sum test were used to investigate the inherent laws and associations between the full flowering stages and the ratio of patients with allergic rhinitis.Result:1Between 2013 and 2014,the early and middle April were the full flowering stages of Platycladus orientalis,Salix matsudana, Fraxinus chinensis,Elms and Birches.The number of patients with allergic rhinitis in outpatient clinic elevated obviously in this period.2There were overlaps of full flowering stages among different plants.During periods in which three or more kinds of pollens in full flowering stages,the consultation rate of patients with allergic rhinitis is higher than less overlaping flower period.The difference was statistically significant(F value were -2.281,-2.964 respectively, P <0.05).Also,there were obvious positive linear correlations between the number of overlap of different pollens and the consultation rate of patients with allergic rhinitis in in 2013 and 2014(r=0.957, 0.964 respectively).Conclusion:During the overlaping flower periods,there was a higher consultation rate of patients with allergic rhinitis.In prevention and treatment of allergic rhinitis,the overlapping effect of full flowering stages of different pollens should be taken into account.Upgrade the alarm level will reduce the incidence of AR and the degree of allergic rhinitis episodes. PMID- 29798331 TI - [The treatment of nose-eye correlated diseases with external nasal incision combined with nasal cavity approach surgery through endoscope]. AB - Objective:To explore the indications and characteristics for the treatment of nose-eye correlated diseases with endoscopic surgery through external nasal incision combined with nasal cavity approach.Method:The clinical data of 13 patients whom hospitalized in our department and treated by endoscopic surgery through external nasal incision combined with nasal cavity approach since October 2011, were retrospectively analyzed and the characteristics of different pathological changes, clinical manifestations, surgical approach and follow-up results were summarized.Four cases of patients underwent endoscopic surgery through nasal cavity and lacrimal caruncle conjunctival incision, 4 cases received bone fracture reduction and DCR with endoscope through double path of nasal cavity and the original trauma wound, 2 cases with endoscopic bone tumor resection through nasal cavity and external nasal incision, the rest of the 3 cases with endonasal endoscopic and peri-orbit incision surgery.Result:Two cases of tumor patients showed no recurrence followed up for 1.5 to 2 years; the diplopia disappeared in 2 cases of orbital medial wall fracture; surgeries of 4 cases of orbital wall fracture with lacrimal duct obstruction patients, 3 cases succeeded, 1 case failed and change into dacryocystorhinotomy with external nasal incision, and epiphora of all patients vanished; all of the patients of sinus osteoma, foreign bodies and abscess were cured and symptoms disappeared; the symptoms of ectopic meningioma patient gradually died down with eyebrow scars left.Conclusion:The surgery with external nasal incision combined with nasal cavity approach through endoscope to treat nose?eye correlated diseases can effectively deal with relevant pathological changes, with the advantages of clear operation field and less damage, but its exact indications and surgical methods still need to be further explored. PMID- 29798332 TI - [Study on Indole-3-carbinol inhibits nasopharyngeal carcinoma cells growth in vitra and in vivo]. AB - Objective:The aim of this study is to investigate the inhibition of nasopharyngeal carcinoma cells by indole-3-carbinol in vitro and in vivo.Method:The human nasopharyngeal carcinoma cell line CNE2 was treated in different concentrations 0,100,200,300 MUmol/L of indole-3-carbinol. Then we detected cell proliferation after 0,24,48 and 72 h, apoptosis after 48 h and the levels of PI3K/Akt pathway-related proteins in vitro. The BALB/c nude mice were divided into three groups: prevention group, treatment group and control group. In vivo, the nude mice in every group were inoculated with nasopharyngeal carcinoma cells CNE2, and mice in prevention and treatment groups were given feed containing 0.5% indole-3-carbinol. We investigated the tumoricidal effect of I3C in nude mice , and eight weeks later, the PI3K/Akt pathway-related proteins expressions in tumors from nude mice of each group were detected.Result:With the indole-3-carbinol concentration increased, cell proliferation decreased and apoptosis increased significantly.The levels of PI3K/Akt pathway-related proteins were decreased.In animal experiments, the prevention and treatment group developed smaller tumors, and the expression of PI3K/Akt pathway-related proteins in prevention and treatment groups PI3K/Akt pathway also reduced, compared to control group. Meanwhile, nearly no changes of heart, liver and kidney tissues in all groups were seen in HE staining.Conclusion:Indole-3-carbinol inhibited the growth of nasopharyngeal carcinoma cells and induced apoptosis effectively in vivo and in vitro. The mechanism might be that indole-3-carbinol could suppress PI3K/Akt pathway. PMID- 29798333 TI - [The expression of MiR-148a in nasopharyngeal carcinoma and its effect on tumor cell biology functions in nasopharyngeal carcinoma]. AB - Objective:Nasopharyngeal carcinoma(NPC) is a common malignant tumor, in recent years,most of studies have found that micro RNA played an important role in the development of NPC.This study was to explore the expression level of MiR-148a and its effect on the biological functions of NPC cells.Method:The expression of MiR 148a in NPC cell line CNE2 was detected by Real-time PCR method.MTT,clone formation assay and flow cytometry were applied to detect cell proliferation and apoptosis. We predicted that EGFR was the downstream target genes of MiR-148a through the analysis of bioinformatics software. Then the expression change of EGFR was measured by Real-time PCR and Western blot.Result:Comparing with normal nasopharyngeal epithelial tissue cells,MiR-148a expression level was significantly reduced in NPC cell line CNE2.MTT,clone formation assay and flow cytometry test show that overexpression of MiR-148a can inhibit cell proliferation and promote cell apoptosis.Real-time PCR and Western blot test show that MiR 148a can reduce the expression of EGFR.Conclusion:MiR-148a can affect the proliferation and apoptosis of NPC cell,and it is likely to be involved in the development and progression of NPC. PMID- 29798334 TI - [The influence on the peeling off time of the tunica albuginea after 4-8C cool water was applied to children's low temperature plasma-assisted tonsillectomy]. AB - Objective:The aim of this study is to discuss the influence on the peeling off time of the tunica albuginea after 4-8C cool water was applied to children 's low temperature plasma?assisted tonsillectomy.Method:One hundred and seventeen benign hypertrophy of tonsil patients were recruited,the 56 cases of them were served as experimental group,who were treated with plasma tonsillectomy using 4-8C normal saline as medium,while the 61 cases were served as control group,who were treated with plasma tonsillectomy using 22-25C normal saline as medium.Then,we analyzed the peeling off time of the tunica albuginea between experimental and control group.Result:The difference of formation time between experimental group and control group was not statistically significant(P >0.05).The average peeling off time of the tunica albuginea was (11.32+/-2.51) days in experimental group,while time was(15.03+/-4.12) days in control group.There was a statistical difference between them.Conclusion:The use of 4-8C cold water in children's low temperature plasma-assisted tonsillectomy can reduce the peeling off time of the tunica albuginea,and it indicate that the ice water medium can reduce the heat injury caused by the plasma operation. PMID- 29798335 TI - [The application of full thicknes skin graft inpartial laryngectomy for glottic carcinoma]. AB - Objective:The aim of this study is to explore the experience and advantages of the application of full thicknes skin graft in glottic carcinoma.partial laryngectomy for glottic carcinoma.Method:One hundred and forty-three patients with glottic cancer were treated with partial laryngectomy.Among those,78 cases were repaired with full-thickness skin graft and 65 cases were repaired with sternohyoid muscular fasciae.Compared the time of extubation and the formation of granulation in laryngeal cavity after operation between the two groups.Result:In the group of full-thickness skin graft,the mean time of decannulation was 6.8 days,5 cases with growth of granulation after operation.In other group,the mean time of decannulation was 10.7 days,16 cases with growth of granulation after operation.The mean time of decannulation(t=-4.739,P<0.01) and the growth of granulation(chi2=9.379,P<0.01) are significantly different between the two groups.No laryngostenosis was found in all patients.Conclusion:The application of full-thicknes skin graft in partial laryngectomy for glottic carcinoma.can shortthe time of extubation and reduce the formation of granulation. PMID- 29798336 TI - [Clinical assessment of the radiotherapy and chemotherapy combined with cetuximabin in the treatment of nasopharyngeal carcinoma]. AB - Objective:The aim of this study is toinvestigate the clinical effect of radiotherapy and chemotherapy combined with cetuximab in the treatment of nasopharyngeal carcinoma.Method:Seventy-eight cases of nasopharyngeal carcinoma patients were divided into control group(n=42) and treatment group(n=36).The control group was treated with radiotherapy and diamminedichloroplatinum;the treatment group was treated with radiotherapy and diamminedichloroplatinum combined with cetuximab.Short-term efficacy,survival time,and adverse reactions were documented during following up in both groups.Result:The efficiency in the treatment group (94.44%) was significantly higher than that in the control group(78.57%),P <0.05.There were no significant difference of adverse reaction including radiodermatitis,oral mucosa reaction,bone marrow inhibition,radiation induced brain injury between the two groups,P >0.05.The medium survival time of the treatment group(55 months) was significantly longer than that of the control group(48 months),P <0.05.4-year survival rate in treatment group(88.89%) was significantly higher than that in the control group(69.05%),P <0.05.4-year diseases free survival(DFS) rate in treatment group(75%) was significantly higher than that in the control group (59.52%),P <0.05.Conclusion:Radiotherapy and chemotherapy combined with cetuximab can significantly improve the treatment efficiency in patients with nasopharyngeal carcinoma,while do not lead to higher rate of adverse reactions.This treatment is worth being promoted in clinical application. PMID- 29798337 TI - [The influence on the function of parathyroid after different thyroid cancer radical operation]. AB - Objective:The aim of this study is to detect the changes of parathyroid hormone and serum calcium levels before and after operation,and evaluate the effect and treatment of parathyroid function after total thyroidectomy.Method:One hundred and seventy-two cases of initial total thyroidectomy were analysed retrospectively,who were divided into simple total thyroidectomy group(A),total thyroidectomy with unilateral central lymph node dissection group(B),and total thyroidectomy with lateral central lymph node dissection group(C).We analyse the preoperative and postoperative serum calcium and parathyroid hormone.Result:In three groups,the serum concentrations of the parathyroid hormone and calcium decreased after operation.The difference was statistically significant between in B group and C group(P<0.05);The hypoparathyroidism had statistical significance between A group and C group(P<0.05).Conclusion:The possibility of hypoparathyroidism and hypocalcemia was increasing with the expansion of the range of operation.Therefore,retain vital recognition of parathyroid gland was very important in the resection of thyroid cancer especially central lymph node dissection.We should reduce the incidence of permanent hypoparathyroidism as far as possible. PMID- 29798338 TI - [Effects of nasal steroids on pulmonary function in patients with allergic rhinitis]. AB - Objective:The aim of this study was to observe the changes of pulmonary function in patients with allergic rhinitis and the effect of nasal glucocorticoid on pulmonary function.Method:Ninety patients with Moderate and severe AR and 50 healthy control subjects were recruited.All participates accepted a pulmonary function test and make a statistical analysis.90 patients of AR were divided into two groups:A group(50) and B group(40).A group treated with nasal budesonide and loratadine,while B group treated with nasal normal saline and loratadine.After 3 months,all patients reviewed the lung function.Result:Comparing with control,FEV1.0/FVC,MMEF,FEF50% and FEF75% reduced significantly in AR group(P<0.01),after 3 months,the treatment of A group compared before:FEV1.0/FVC(P<0.05),MMEF,FEF50% and FEF75%(P<0.01) had statistical significance.Compared B group after the treatment:FEF75% (P<0.05) was significant.After the treatment of group A compared with normal group:there was no significance.Conclusion:The reduced pulmonary function of allergic rhinitis paitents is mainly due to the small airway dysfunction.Budesonide is superior to loratadine to improve the pulmonary function. PMID- 29798339 TI - [The effect and treatment of reflux throat on laryngeal function and wound healing after CO2 laser laryngeal microsurgery]. PMID- 29798340 TI - [Clinical application of contrast-enhanced ultrasound in the differential diagnosis of properties of patients with Hashimoto's thyroiditis and thyroid nodules]. PMID- 29798341 TI - [Safety analysis of head and neck surgery for short-necked obese patients accompanied by sleep-disordered breathing]. PMID- 29798342 TI - [Report and analysis of 2 cases of nerve paralysis with aspiration pneumonia after infection of herpes zoster virus]. AB - Two cases of patients were hospitalized for sore throat with Dysphagia.Check:Wall of the pharynx,tongue and epiglottis scattered the ulcer.The patients were loss of pharynx reflex.Oropharynx and piriform fossa has a lot of saliva retention.Posterior pharyngeal wall was drooping like waterfull.CT scan showed may be the aspiration pneumonia in right lower lung.The admission diagnosiswere pharyngeal herpes zoster virus infection,pharyngeal side muscle paralysis,and inhalation pneumonia.The patients' clinical data were retrospectively analyzed,and the report is as follows. PMID- 29798343 TI - [The diagnosis and treatment of thyroid microcarcinoma]. AB - Thyroid microcarcinoma(TMC)refers to the diameter less than 1 cm in thyroid carcinoma.With the development of high frequency ultrasound and pathological diagnosis technology,the incidence of TMC increased.Preoperation examination methods include routine ultrasound,ultrasound elastography,CT and fine needle aspiration biopsy.But its treatment methods are controversal.In this paprer,we review the present status in the diagnosis and treatment of thyroid microcarcinoma. PMID- 29798347 TI - [The role of ATA (2015) guidelines, superb microvascular imaging, and spectral Doppler in differentiation between malignant and benign thyroid nodules]. AB - Objective:To evaluate the diagnostic value of ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines, color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and spectral Doppler in the differentiation of benign and malignant thyroid nodules.Method:The study included 254 thyroid nodules confirmed by fine needle aspiration cytology (FNAC) or histopathologic examination. All nodules were detected by ultrasonography, SMI, CDFI and spectral Doppler respectively. Blood flow detection technologies (CDFI and SMI) were used to classify flow distribution characteristics of thyroid nodules according to Kim's grading criteria. The optimal threshold drawing from ROC curve is calculated to obtain the cut-off value of spectral Doppler.Result:1For benign solid nodules with peripheral flow distribution and malignant solid nodules with central blood flow distribution, the display rates of SMI are higher than those of the CDFI, the differences were statistically significant (P< 0.05). 2There was a significance difference in detecting benign and malignant nodules using spectral Doppler (P< 0.05). 3The specificity and accuracy of combinative modality 2015 ATA+SMI was significantly higher than that of ATA, SMI, and spectral Doppler. There was no significant difference between ATA+SMI and ATA+SMI+spectral Doppler for the sensitivity, specificity, and accuracy.Conclusion:SMI had a better detection rate of blood vessels than CDFI and contribute a certain value in differential diagnosis of benign and malignant thyroid nodules. The combination of 2015 ATA and SMI can improve diagnostic value in the differentiation between benign and malignant thyroid nodules. PMID- 29798344 TI - [A systematic evaluation of the assessment methods of spasmoidc dysphonia]. AB - To review the available subjective and objective evaluation methods used in the assessment of the spasmodic dysphonia.A systematic literature search was conducted in PubMed,web of science,EBSCO and Ovid database,date limited from 2000 to 2015,language limited English,using the following key words: "spasmodic dysphonia" OR "spastic dysphonia" AND "evaluat*" OR " diagnosis" OR "treatment" OR "assess*".Screening the titles and abstracts,and reading the full text,studies met the inclusion criteria were enrolled.The references of eligible publications were manually searched to identify additional studies.A total of 967 literatures were retrieved.Finally,twenty-three papers were enrolled in the study according to the inclusion criteria.Evaluation methods were mainly divided into subjective and objective,including perception,subjective self-assessment;and aerodynamic,acoustic analysis,respectively.The assessment of spasmodic dysphonia should be multidimensional. PMID- 29798345 TI - [Risk factors of central neck lymph node metastasis in cN0 papillary thyroid carcinoma]. AB - Objective:To investigate the risk factors of central neck lymph node metastasis (CNLNM) in cN0 papillary thyroid carcinoma. Method:Retrospective analysis of 114 patients with papillary thyroid carcinoma in stage of cN0 who underwent primary treatment. Collected the clinical and pathological data, used the univariate and multivariate analysis to investigate the risk factors of central neck lymph node metastasis and high volume central neck lymph node metastasis.Result:In the univariate analysis, age (48.2% in<45 years vs 27.6% in>=45 years), multifocal (51% with vs 27.7% without), nodular goiter (58.8% with vs 28.7% without), showed significant difference in prevalence of CNLNM. Age (14.3% in<45 years vs 1.7% in>=45 years), tumor size (19.2% >1 cm vs 4.5%<=1 cm) showed significant difference in prevalence of high volume CNLNM. Inmultivariate analysis, age (RR= 0.304), multifocal (RR= 3.637) and nodular goiter (RR= 4.132) showed the independent risk factor of CNLNM.Conclusion:For cN0 patients with thyroid papillary carcinoma, if the age is younger than 45 years old, the tumor is multifocal, or associatedwith nodular goiter, the surgery should be more aggressive in the prophylactic central neck dissection. PMID- 29798350 TI - [Radiographic analysis for infarcted angiomatous polyps in maxillary sinus]. AB - Objective:To explore the CT, MRI manifestations of the polyp of maxillary sinus cavernous hemangioma. To summarize the imaging characteristics and it may assist doctors to diagnose infarcted angiomatous polyps in maxillary sinus with further developing.Method:A retrospective analysis of the CT, MRI manifestations and clinical analysis about 27 cases confirmed by surgery pathology who are maxillary sinus cavernous hemangioma.Result:Twenty-seven cases were unilateral diseases, and clinical manifestations were nasal congestion. Twenty-seven cases were proceeded CT scan, of which 9 cases of double-phase dynamic enhanced CT examination, 11 cases with MRI examination, of which 6 cases with MRI enhanced examination. CT scan showed unilateral maxillary sinus full of mixed density and involving the nasal cavity, maxillary sinus abnormal expansion of deformation, with local bone resorption damage in 27 cases, but without violation the adjacent tissue. CT enhanced scan of lesions shows that the spotted blood vessels were significantly enhanced and progressive enhancement. MRI can clearly identifylesions and obstructive sinusitis and morbid shape was irregular with mixed signal. T2WI showed high and low mixed ring signals, and the edge of the irregular low signal ring, with enhanced nodules and patchy unevenly enhanced.Conclusion:Most polypof maxillary sinus cavernous hemangioma clinical manifestations are unilateral nasal obstruction. CT shows the maxillary sinus irregular expands and compression bone absorption with a prompt action to this disease.Vascular-like enhancement and progressive enhancement are characteristic enhanced CT manifestations of this disease. MRI can better show the lesion range. T2WI with high and low ring mixed signals, low ring signals, and mostly enhanced nodules, uneven enhancement of plaqueare characteristic imaging manifestations. PMID- 29798351 TI - [Analysis of related factors of recurrent otitis media with effusion in children]. AB - Objective:To investigate the influencing factors of recurrent episodes of otitis media with effusion in children.Method:A retrospective summary of the clinical data of 210 cases of children with otitis media with effusion, 75 cases of recurrence after treatment, 135 cases were recovered, the recurrence of the related factors and after symptomatic treatment effect is analyzed.Result:Logistic regression analysis results found that adenoid hypertrophy (III degrees , IV degrees ), tonsil hypertrophy (IV degrees ) and sinusitis (including choanal polyp), a positive allergens, upper respiratory tract infection, the stomach esophagus regurgitation, cleft palate, younger age has significant effect on recurrence of otitis media with effusion, have significant difference (P< 0.05). And the influence of duration, gender, passive smoking history and previous medical history of otitis media with effusion has no obvious statistical significance (P> 0.05). Through the comparison among different age groups, adenoidectomy III degrees , IV degrees hypertrophy tract infections in > 3-6 years old group has significant effect (P< 0.05), recurrent respiratory tract infections in less than 3 years old group and the group of children aged > 3-6 years OME recurrence has significant effect (P< 0.05). By tympanocentesis or tympanostomy tube insertion and according to different conditions to take symptomatic treatment, 75 cases (123 ears) were cured 96 ears (78.05%), 19 ears were improved (15.45%), the total effective rate was 93.50%, ineffective in 8 ears (6.50%).Conclusion:Adenoid hypertrophy (III degrees , IV degrees ), tonsil hypertrophy (IV degrees ), sinusitis, nasal polyps, allergic diseases and upper respiratory tract infection gastroesophageal reflux, cleft palate and younger age may be adverse factors related to recurrent otitis media with effusion in children, the clinical doctors should pay attention to these symptoms, according to different causes, adopt individualized treatment plan, make children get the best treatment as soon as possible. PMID- 29798353 TI - [High mobility group box1 contributes to hypoxia-induced barrier dysfunction of nasal epithelial cells]. AB - Objective:To investigated the promotion of high mobility group box1 (HMGB1) under hypoxia, and determined the regulatory role of HMGB1 on the barrier function of nasal epithelial cells.Method:Primary nasal epithelial cells (NECs) collected from patients with septal deviation were cultured at air-liquid interface. The release of HMGB1 under hypoxia was detected by ELISA. The effect of HMGB1 on fluorescein isothiocyanatedextran 4 kDa (FD4) permeability of NECs was measured. Western blot analysis was utilized to examine the level of major junction proteins, namely E-cadherin, ZO-1, Occludin and Claudin-1.Result:The release of HMGB1 was significantly upregulated in NECs under hypoxia. Recombinant human HMGB1 increased FD4 permeability in a dose and time-dependent manner, indicating the impaired epithelial barrier function. HMGB1-mediated barrier hyperpermeability was accompanied by the selective downregulation of ZO-1, occludin and Claudin-1, but not E-cadherin.Conclusion:HMGB1 mediates hypoxia induce barrier dysfunction of nasal epithelium, which may be a potential target for the treatment of chronic rhinosinusitis. PMID- 29798349 TI - [The measurement of pneumatization of maxillary sinus extended into alveolar process basing on the CT and its clinical significance]. AB - Objective:To investigate the significance of pneumatization of maxillary sinus extended into alveolar process.Method:One hundred outpatients encountered were included in this study. The pneumatizations of maxillary sinus extended into alveolar process were observed and classified. Depth of surgical procedure of maxillary sinus in different type was measured.Result:The actual depth of surgical procedure of maxillary sinus of in different types of the alveolar process pneumatization varied greatly. The actual depth of surgical procedure of maxillary sinus in type III pneumatization of alveolar process were (32.27+/ 3.48)mm, which were significantly deeper than type II (28.35+/-3.45)mm and type I(20.73+/-3.09)mm (P< 0.05 respectively). Moreover, the actual depth of surgical procedure of maxillary sinus in type II was also deeper than type I(P< 0.05).Conclusion:The pneumatization of maxillary sinus extended into alveolar process can significantly affect the actual depth of the maxillary sinus in the operation of endoscopic middle meatus antrostomy, which may serve as a reference for the choice of endoscopic maxillary sinus approaches. PMID- 29798348 TI - [Clinical analysis of tympanoplasty combined with ventilation tube insertion in otitis media]. AB - Objective:The aim of this study is to explore the feasibility and clinical effect of tympanoplasty combined with ventilation tube insertion in otitis media.Method: Retrospective analysis of 35 patients with eustachian tube obstruction or tympanic adhesions for tympanoplasty combined with ventil ation tube insertion in otitis media in EENT Hospital of Fudan University from April 2008 to December 2010. Preoperative routine hearing tests and temporal bone CT examination. Completely remove of lesions at the same time and as much as possible to protect the integrity of the tympanic wall mucosa during operation. Reconstruction of the ossicular chain and simultaneous tympanic membrane hole and placed silicone T type ventilation tube. All patients were tested for pure tone auditory threshold at 3 months after operation. The patients were followed up for 12 to 44 months.Result:The average hearing level of PTA (0.5,1.0,2.0 kHz) was (31.71+/ 12.25) dBHL. 28 cases (80.0%) had improved to 40 dBHL after operation, 5 cases (14.3%) had hearing enhancement of 10-20 dBHL, and 2 patients (5.7%) had no change in hearing. The number of cases with air bone gap (ABG)(0.5, 1.0, 2.0 kHz) reduced to less than 20 dBHL was 25, 32 and 34 after operation. Ventilation tube self-prolapse in15 cases, 12 cases of artificial removal and 8 cases of inpatient. Twenty seven cases were left perforation of tympanic membrane, of which 22 cases (81.5%) were spontaneously healed and 5 cases(18.5%) were left with small perforations less than 2 mm in diameter. All of them had dry ear after operation, none of them had recurrence after operation, 33 cases (94.3%) had dry ear within 12 weeks, and only 2 cases(5.7%) had dry ear for more than 6 months.Conclusion: Tympanoplasty combined with ventilation tube insertion for the middle ear mucosal dysfunction and eustachian tube mucosal dysfunction of otitis media treatment effect is obvious. It does not extend the dry ear time and cause postoperative recurrence. This operation is feasible, reliable and effective. PMID- 29798352 TI - [Clinical application of the dynamic adenoidal hypertrophy ratio in the evaluation of illness severity in children with OSAHS]. AB - Objective:To evaluate application value of the dynamic adenoidal/hypertrophy (A/N) ratio in children with OSAHS by analyzing the correlation between the A/N ratio at the different respiratory phases and the index of polysomnography.Method:Fifty-one childrens, with simple hypertrophic adenoids, were diagnosed as OSAHS. Magnetic resonance imaging (MRI) with respiratory gating technology were used to scan the upper airway of children during sleep at the early, middle and end phases of respiratory cycle, and measure adenoidal hypertrophy ratio in different respiratory phases. The correlation analysis was performed between the A/N ratio in different respiratory phases and the index of polysomnography (AHI and LaSO2). Finally, via ROC curve and Kappa analysis, the critical value and diagnosis accordance rate of A/N ratio in illness severity evaluation of children with OSAHS were confirmed.Result:At the 6 respiratory phases, the A/N ratios showed significantly positive correlations with AHI (All P< 0.01). There was a highest coefficient between the end-expiratory A/N ratio and AHI (r= 0.559 4). In addition, the optimal cut-off point of A/N ratio between slight-moderate and severe OSAHS was 0.834. The diagnosis accuracies of the end expiratory A/N ratio in severe and slight moderate OSAHS were 81% and 84%, respectively.Conclusion:MRI with respiratory gating technology obtaining dynamic A/N ratio might be an important method of imaging diagnosis of children OSAHS, and the end expiratory A/N ratio is expected to become a classification index of slight moderate and severe children OSAHS. PMID- 29798346 TI - [Clinical symptoms and immunology inspection characteristics of nasal cavity local allergy]. AB - Objective:To investigate the clinical symptoms and immunology inspection characteristics of nasal cavity local allergy. Method:Selected 60 patients as observation group, who had only nasal local allergy symptoms, allergen skin prick test and serum allergen specific IgE (SIgE) test were negative, 40 allergic rhinitis (AR) patients and 40 healthy volunteers as control groups. To detect Symptom scores and VAS scores, and eosinophilia counts in venous blood, allergen skin prick test (SPT), serum allergen SIgE test, nasal secretions allergen SIgE test, nasal mucous membrane excitation test in both observation group and AR group, eosinophilia counts in nasal secretion, taked the data for statistical analysis.Result:There was no difference (P> 0.05) in the symptom scores and VAS scores of observation group and the AR group. The eosinophilia counts in venous blood in the AR group were higher than in the observation group (P< 0.05). The eosinophilia counts in venous blood in the observation group were higher than in the healthy volunteers group (P< 0.05). The positive rate of nasal secretions dust mites and pollen allergen was 90% (54/60) in observation group. There was no significant difference (P> 0.05) in the eosinophilia percentages in nasal secretion in the observation group and the AR group. There was significant difference (P< 0.05) in the eosinophilia percentages in nasal secretion in the observation group and the healthy volunteers group. There were 6 patients in observation group whose nasal secretions allergen SIgE test and nasal mucous membrane excitation test were both negative, could be diagnosised as non-allergic rhinitis (NAR). According to eosinophilia counts in venous blood and nasal secretions, 4 patients were diagnosised as vasomotor rhinitis and 2 patients were diagnosised as NAR with eosinophilia syndrome. There were 54 patients in observation group whose nasal secretions allergen SIgE test and (or) nasal mucous membrane excitation test were positive, could be diagnosised as local allergic rhinitis. After three years, all of the observation group patients were detected with SPT and serum allergen SIgE test. Five patients diagnosed as local allergic rhinitis before three years were positive. Six patients diagnosed as NAR before three years were negative.Conclusion:For patients with the typical medical history and symptoms of AR, but allergen SPT and serum allergen SIgE test were negative, there was local specific hypersensitivity in nasal mucosa, but the reaction was not accompanied by systemic sensitization. Combined with nasal secretions allergen SIgE test or allergen nasal mucosa proocation tests positive, could be diagnosed as local allergic rhinitis. PMID- 29798354 TI - [The clinical signifinace of CEA, Cyfra21-1 and SCC in laryngeal carcinoma's clinicopathological parameters]. AB - Objective:To investigate the clinical signifinace of carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (Cyfra21-1) or squamous cell carcinoma antigen (SCC) in laryngeal carcinoma's clinicopathological parametersthe.Method:CEA, Cyfra21-1, SCC in 53 laryngeal cancer's serum were routine preoperative detected to analyze the relationships between the tumor makers and the patient's age, primary tumor (T staging), lymph node metastasis (N staging), recurrence and metastasis.Result:According to age less than or equal to 60 years old and older than 60 years, lymph node metastasis or not lymph node metastasis, with or not with recurrence and metastasis and the T1+T2 and T3+T4 staging, the patients were divided into two groups. T test show that CEA was statistically significant in recurrence and metastasis (P= 0.047) and it is more prone to recurrence and metastasis, but CEA was not statistically significant in primary tumor (P= 0.252), lymph node metastasis (P= 0.268). Cyfra21-1 was not statistically significant in primary range (P= 0.402), but was statistically in lymph node metastasis (P= 0.041). While the lymph node metastasis, it is more prone to recurrence and metastasis in laryngeal cancer patients with Cyfra21-1's increasing (P= 0.027). SCC was not significant in primary lesions (P= 0.051),but was statistically significant in lymph node metastasis (P= 0.022). While lymph node metastasis, it is more prone to recurrence and metastasis in laryngeal cancer patients with SCC's increasing (P= 0.000). Logistic multivariate regression analization show that CEA,Cyfra21-1 and SCC were statistically significant in the recurrence and postoperative of laryngeal patients (P< 0.05) but not in the age of patient, primary tumor, the relationship and lymph node metastasis (P> 0.05).Conclusion:It is more prone to occurrence lymph node metastasis and recurrence and metastasis in the postoperative serum of laryngeal cancer patients with Cyfra21-1, SCC. CEA and Cyfra21-1 increasing. SCC were independent predictive factor of recurrence and metastasis after surgery. It is more prone to recurrence and metastasis after surgery in the laryngeal cancer patients with CEA, Cyfra21-1 and SCC preoperative increasing. PMID- 29798359 TI - [Diagnosis and treatment of 204 cases of metallic foreign bodies aspiration in children]. PMID- 29798356 TI - [Analysis of sonographic characteristics of thyroid nodules diagnosed as false positive or negative results in shear wave elastography]. AB - Objective:In order to improve diagnostic accuracy, we study the characteristics of two dimensional ultrasound and shear wave elastography in the diagnosis of false negative or false positive thyroid nodules by shear wave elastography.Method:One hundred and eighty-nine nodules in 189 consecutive patients who had been determined by surgical operation and pathology. Conventional ultrasound features and SWE elasticity imaging characteristics and properties of the final postoperative pathology were recorded. A comparative study between true and false results of quantitative SWE elasticity imaging, and the corresponding conventional ultrasound nodule characteristics were compared.Result:Postoperative pathology showed 189 nodules, 74(39.2%) were benign and 115(60.8%) were malignant. The sensitivity, specificity of conventional ultrasound in the diagnosis of thyroid nodules were 56.5% and 81.1% respectively, and those of SWE were 60.9% and 85.1%. The false positive rate of shear wave elastography in diagnosing benign nodules and the false negative rate of malignant nodules were 14.9% and 39.1%, respectively. The false negative rate was higher than the false positive rate. A vertical growth (P< 0.01) and smaller diameter of the masses were significantly associated with false SWE findings (P< 0.01).Conclusion:The SWE imaging has important significance for differentiating benign and malignant thyroid nodules, but false results are inevitable, which requires clinicians conjunction with other test results to prevent errors judgment when reviewing the SWE imaging. PMID- 29798357 TI - [Endoscopic sinus surgery for the treatment of invasive fungal sinusitis]. AB - Objective:To explore the early diagnosis, the treatment and theprognosis of invasive fungal rhinosinusitis.Method:By summarizing the clinical data of 18 patients, CT and MRI images, pathological diagnosis and follow-up results to analysis the early diagnosis and the treatment.Result:All 5 patients with invasive fungal sinusitis were infected with mucor, 3 of whom died of intracranial complications. Among 13 patients with chronic invasive fungal rhinosinusitis, 9 were aspergillus, 3 were mucor, and 1 was negative. There were 9 cases of diabetes, 1 cases of ankylosing spondylitis, 3 cases of hypoproteinemia, 1 cases of organ transplantation, and 1 cases of leukemia. There were 3 cases of death who unenforced the operation, 15 patients received enlarged endoscopic surgery, postoperative antifungal therapy. Followed up 1-3 years, relapse in 3 cases, 1 case of death.Conclusion:The diagnosis of FRS needs to be combined with clinical manifestations, imaging features and pathological findings. The treatment requires surgery to completely remove diseased tissue (enlarged sinus open surgery) combined with antifungal use in sufficient quantities. PMID- 29798355 TI - [Endoscopic transoral resection the tumors of the higher position in parapharyngeal space: a retrospective case-control study]. AB - Objective:To analysis the indication and security of the endoscopic resection of transoarl and pterygoid process approach of neoplasms in elevatus parapharyngeal space.Method:A retrospective case-control study were carried out in 22 patients with parapharyngeal space tumors.In the observation group (11 patients), tumors were endoscopic resected by transoral and pterygoid process approach. Paired with 11 patients (control group) who underwent surgry by traditional approach. We compared the en bloc resection rate, the operation time, blood loss, postoperative hospital stay, complication rate between the two groups.Result:In the observation group, the operation time, the blood loss and the postoperative hospital stay was (122.45+/-22.2)min, (97.26+/-13.75)ml, (4.09+/-1.22)d respectively. While in the control group, the operation time, the blood loss and the hospitalized days was (134.36+/-20.38)min, (213.64+/-63.99)ml, (5.10+/-0.99)d respectively. There were tumors that were block resection in both groups. In the observation group, there were a recurrence. Comparing the operation time, en bloc resection rate and postoperative hospital stay, there were no significant differences. There were differences in bloods loss between the two groups.Conclusion:The endoscopic transoral resection the tumors of the higher position in parapharyngeal space is safe, minimally invasive and feasible in selected cases, with a high local control rate and a low surgical complication rate. PMID- 29798358 TI - [Imaging-navigated endoscopic surgery in acute pediatric sinusitis with orbital subperiosteal abscess: two cases report]. PMID- 29798360 TI - [Laryngeal undifferentiated soft-tissue sarcoma: a case report and review of literature]. AB - Patient presented as a 74-year-old male complaining of hoarseness. Electronic laryngoscope showed a neoplasm whose size was about 1.0 cm*0.5 cm*0.5 cm at anterior commissure. A surgery was conducted to excise the neoplasm en bloc. The histopathological and immunohistochemistry examination suggested inflammatory myofibroblastic tumor. A month later, the patient presented with dyspnea and blood-stained sputum. CT scan of neck showed an occupation lesions under glottis. A tracheotomy and a CO2 laser surgery was conducted due to patient's will. The histopathological and immunohistochemistry examination suggested undifferentiated sarcoma. We advised him keeping a tracheal cannula to receive further treatment such as radiotherapy or chemotherapy in oncology department, but the patient was not compliant with care instructions for personal reason. He was readmitted 2 months later for dyspnea after plugging the tube. Electronic laryngoscope showed a large neoplasm occupied the laryngeal vestibule, covering the glottis. CT and MRI scan showed the lesion involved spaces of supraglottic, glottic, subglottic and soft tissue around larynx. Hence, a total laryngotomy and bilateral functional neck dissection was conducted. The histopathological examination agreed with the former one. Three weeks later, the skin around his tracheal cannula swelled,ulcerated and pyorrheal. After 10 days of dressing change, patient died of uncontrolled infection. PMID- 29798361 TI - [Two cases of carotid sheath ectopic thyroid carcinoma]. AB - Ectopic thyroid tissue is resulting from developmental defects at early stages of thyroid gland embryogenesis. It can be found in many sites,including the tongue, pharynx, hyoid and throat. Ectopic thyroid tissue may also be involved in the same pathological processes as normal, or hotopic thyroid gland. These processes include tumors, inflammation and hyperplasia. They can cancerization, and the treatment of ectopic thyroid carcinoma is also controversial. The appearance of such tissue in rare locations may lead to diagnostic and therapeutic dilemmas. PMID- 29798362 TI - [The relationship between incidence of secretory otitis media and passive smoking in children]. AB - Children with secretory otitis media are often the result of multiple factors. Recent epidemiological studies on its incidence have mentioned the effects of passive smoking on its incidence. This article explores the potential links between the two by summarizing relevant literatures. PMID- 29798363 TI - [An association between obstructive sleep apnea hypopnea syndrome and deep vein thrombosis and pulmonary embolism]. AB - OSAHS is a kind of the sleep-related breathing disorder, with lack of oxygen. OSAHS can induce many kinds of cardiovascular system diseases. Deep vein thrombosis and pulmonary embolism (deep vein thrombosis and/or pulmonary embolism, DVT and PE) is caused by deep vein thrombosis embolism pulmonary artery trunk or branch pulmonary disorder, potentially lethal diseases of the cardiovascular system. In recent years, researchers have found that OSAHS may have something to do with DVT-PE. So in this review, the relationship was summarized between OSAHS and DVT-PE in epidemiology, pathophysiology, assessment and treatment measures. PMID- 29798364 TI - [Current status of treatment of laryngeal contact granuloma]. AB - Laryngeal contact granuloma, also known as vocal cord granuloma, is the non neoplastic inflammatory granulation tissue occurring in the vocal cord around. The cause is unclear, morbidity and cure rate is low, the recurrence rate is high, leading to a poor clinical treatment. But some symptoms of the sound disorder, pharyngeal foreign body sensation seriously affect the quality of life of patients, increase the psychological burden of patients. With the increasing awareness of the disease, the deepening of the research, there have been different treatment methods. This paper reviews the previous literatures, and summarizes LCG treatment for the status. PMID- 29798365 TI - [Standardization of diagnosis and treatment in chronic otitis media]. PMID- 29798366 TI - [Classification, diagnosis and surgical management of chronic suppurative otitis media]. PMID- 29798367 TI - [Bone conduction in tympanosclerosis patients and its changes after surgery for tympanosclerosis]. AB - Objective:To investigate the bone conduction (BC) in tympanosclerosis patients and its changes after surgery for tympanosclerosis, as well as its possible causes.Method:Retrospectively analyzed 30 cases of tympanosclerosis patients.Result:Before surgery, the average BC of the operated ear was (21.06+/ 8.88) dBHL, the average BC of the healthy side was (16.78+/-8.97) dBHL, the difference had a statistical significance (t= 3.072, P< 0.01). The BC threshold, air conduction (AC) and ABG were significantly lower after operation. Preoperative BC at 2 000 Hz was the highest threshold (25.17+/-10.95) dBHL, and the postoperative decrease of BC thresholds at 500 Hz, 1 000 Hz and 2 000 Hz were statistically significant (P< 0.05 or P< 0.01). Tympanoplasty with mastoidectomy for BC threshold improvement was better than only tympanoplasty (P< 0.05)Conclusion:Tympanosclerosis leads to elevated BC threshold. Removal of tympanosclerosis lesions together with the removal of the lesions in antrum and mastoid and the reconstruction of sound conduction structures not only improve AC hearing and shorten ABG, but also improve postoperative BC hearing significantly. PMID- 29798368 TI - [Effect of intratympanic injection of budesonide for otitis media with effusion in adolescents and adults]. AB - Objective:To assess the longitudinal curative effect and improvement of subjective symptoms by using intratympanic injection of budesonide (BUD) for OME patients over 12 years old and adults.Method:One hundred and eighty patients who were diagnosed as OME were recruited. A single-blind, randomized, parallel control prospective study was performed. Dexamethasone (DEX) and sodium chloride (NS) were served as controls. The patients were randomly assigned into three groups, which respectively received intratympanic injection of BUD (0.5 mg/ml), DEX (5 mg/ml) or 0.9% NS solution (1 ml) once a week. Survival analysis was applied to compare the longitudinal curative effect among the three groups. Meanwhile, seven main subjective symptoms were scored by 10-point visual scale (VAS) and physician's evaluations were preformed during treatment and follow up.Result:After adjustement for course of disease, volume and characters of effusion, the relative risk (RR) of BUD was 0.131 (95%CI: 0.053-0.354) when compared with NS. Survival curve showed, in BUD group, about 96.6%(57/59) of patients maintained effectiveness more than 3 months, 83.1%(49/59) were more than 1 year, and 81.4%(48/59) of the patients could sustain longer than 3 years. In DEX group, 73.2%(41/56) of patients showed effectiveness more than 3 months, 46.4%(26/56) were more than 1 year, and 42.9%(24/56) of the patients could sustain longer than 3 years. While in NS group, 50.8%(33/65) of the patients showed effectiveness more than 3 months, 26.2% (17/65) were more than 1 year, and 20.0%(13/65) of the patients could sustain longer than 3 years. Survival curve demonstrated that the rank of longitudinal therapeutic efficacy was BUD, DEX and NS (P< 0.05). Both BUD and DEX showed improvements in subjective symptoms and quality of life (except for mental stress) compared with NS (P< 0.05). In the aspect of improving the symptom of stuffy ear, BUD showed advantage over both DEX and NS. During and after treatment, no serious complications or sequelae were observed.Conclusion:Intratympanic injection with BUD for OME patients showed advantages in improving long-term therapeutic efficacy, it was a safe as well as effective intervention for children over age of 12 and adults suffering from OME. PMID- 29798369 TI - [Clinical observation on the treatment of intractable otomastoiditis with reconstruction of external auditory canal wall]. AB - Objective:To observe the clinical effect on the treatment of intractable tympanitis with reconstruction of external auditory canal wall.Method:Five cases underwent radical removel of residual lesion and reconsruction of external auditory posterior canal wall using hydroxyapatite ceramic wall with transferred pedicle temporalis fascia covering on it were analyzed. The implement of ossicular chain reconstruction depends on the probing for tympanic cavity intraoperatively. Periodic review were conducted in the 1st, 3rd, 6th, 12th month after surgery.Result:All 5 cases gained dryears within 3 months after surgery, in which hearing of 3 cases improved and ABG were within 20 dB. 1 cases showed no improvement compared to preoperation, and 1 case gained a worse audiology result. Central part of the transplant of 1 case was naked, while peripheral part had been epithelization and external auditory canal gained no accessible to mastoid cavity, the patient were also found recurrence of cholesteatom inside the mastoid cavity when received CT examination during outpatient follow-up one year postoperatively, and underwent correction surgery. 1 case underwent revision operation for a fistula between the reconstructed wall and the skin of the outer auditory canal. No surgical complications like infection or facial paralysis occurred, all patients were satisfied with surgery effect.Conclusion:HA with transferred vascularized temporalis fascia pedicle for the reconstructon of the external auditory canal wall is an effective method for the treatment of intractable tympanitis, and worth promoting. PMID- 29798370 TI - [Screening for effective antibiotics in chronic suppurative otitis media]. AB - Objective:To explore the method of screening effective antibiotics in active stage of otitis media, in order to lay ground for rational clinical application of antibiotics in this scenario.Method:The clinical data of 198 patients diagnosed as otitis media were analyzed. Based on the results of bacterial culture and drug sensitivity test of middle ear secretion, the clinical availability and the ototoxicity of corresponding drugs, first and second line drugs were screened to control infection. The therapeutic effect of drugs was summarized.Result:In 21 out of 198 cases, there was no growth of common bacteria, while in the remaining 177 cases, there were 36 cases(20.34%) of coagulase negative staphylococcus, which was sensitive to linezolid, vancomycin, cefuroxime, levofloxacin, SMZ-TMP, and rifampin; 30 cases(16.95%) of pseudomonas aeruginosa, which was sensitive to meropenem, imipenem, ceftazidime, amikacin, and piperacillin; and 26 cases(14.69%) of staphylococcus aureus, which was sensitive to linezolid, vancomycin, oxacilin, gentamycin, levofloxacin, ciprofloxacin, moxifloxacin. Drugs that were administrated based on experience including: local use of levofloxacin eardrops, cefuroxime and moxifloxacin as first line oral antibiotics, and ceftazidime as second line oral antibiotics. There were 3 cases of post-operational infection, which recovered after systemic and local use of sensitive drugs and dressing.Conclusion:In otitis media, sensitive antibiotics chosen from results of bacterial culture and drug sensitivity test, are useful in reducing the complication of infection after surgery. PMID- 29798371 TI - [The surgical treatment of middle ear cholesteatoma complicated with peripheral facial paralysis (with 22 cases)]. AB - Objective:To summarize the clinical characteristics, the surgical methods and the recovery of facial nerve function outcomes in patients with the middle ear cholesteatoma complicated with peripheral facial paralysis.Method:Retrospective analysis method was used on patients treated for middle ear cholesteatoma associated with peripheral facial paralysis. Facial nerve decompression and great auricular nerve grafting were performed for restoration of facial nerve. Facial nerve function was assessed with the House-Brackmann (H-B) grade scale. Spearman test was employed for statistic analysis.Result:Surgical exploration revealed that the cholesteatoma was mainly located in epitympanic cavity, mastoid and sinus tympani, which mainly damaged the tympanic segment of facial nerve. Nineteen cases with facial nerve edema, including complete sheath (n=15) and sheath defect (n=4), were performed decompression. Among which 15 recovered to H B I, 3 recovered to H-B II, 1 recovered to H-B IV. Three cases with facial nerve disrupt underwent great auricular nerve grafting, 1 recovered to H-B IV, 2 recovered to H-BV. The rate of recovery to H-B I or II in patients underwent surgery within 2 weeks was 92.3%(12/13).Conclusion:When the middle ear cholesteatoma complicated with peripheral facial paralysis, surgery should be carried out as soon as possible. After removed the cholesteatoma completely, facial nerve decompression could acquire a better facial nerve function recovery compared to great auricular grafting. PMID- 29798372 TI - [A retrospective study of 54 cases with chronic otitis media prepared for staging tympanoplasty]. AB - Objective:To analyze the clinical effect of 54 cases with chronic otitis media prepared for staging tympanoplasty and 19 cases finished staging ossicular reconstruction surgery, evaluate the advantages of different surgery technique.Method:Fifty-four cases with chronic otitis media were planned for staging tympanoplasty surgery and had been received the first stage surgery. Silicagel plates were placed in the tympanic cavity in order to prevent adhesions. Among them, 19 cases had received the second stage ossicular reconstruction, including 10 cases with TORPs and 9 cases with PORPs. The average air bone gaps (ABG) were measured at four frequencies: 500, 1 000, 2 000 and 4 000 Hz.Result:Among the 54 cases, 45 cases had swollen mucosa in the tympanic cavity and eustachian tube, 18 cases had tympanic fibrous adhesions, and 12 cases had fixed or sclerotic stapes. The preoperative ABG of the 54 cases were (38.26+/ 7.88)dB. As for the 19 cases finished the second stage surgery, their preoperative ABG in the first stage were (39.21+/-7.05)dB, the preoperative ABG in the second stage were (38.82+/-11.43)dB, and the postoperative ABG after the second stage were (21.77+/-11.92)dB. The hearing function after staging tympanoplasty was significantly improved compared with the preoperative hearing in the first and the second stage operation (P< 0.01). In addition, the second stage surgery of three cases was postponed because of a good postoperative hearing with (10.42+/-10.63)dB ABG after the first stage surgery. Up to now, none of the 54 cases suffered from facial palsy, infection and other complications after surgery.Conclusion:Staging tympanoplasty is an important technique to improving hearing and reducing the complications, especially for the cases with chronic otitis media unsuitable for one stage reconstruction of ossicular chain. PMID- 29798373 TI - [Immediate reconstruction of facial nerve defect using cable grafting of the greater auricualr nerve after parotid cancer resection]. AB - Objective:To evaluate the feasibility of immediate reconstruction of facial nerve defect by using cable grafting of the greater auricular nerve after parotid cancer resection.Method:Clinical data of 11 patients suffering from parotid cancer was reviewed.9 cases were diagnosed as mucoepidermoid carcinoma and 2 cases were adenoid cystic carcinoma. Total parotidectomy and elective neck dissection were performed before cable grafting of the greater auricular nerve was interposed between stumps of facial nerve trunk and its branches. The facial nerve electromyogram and symmetry of mimetic musculature were evaluated. The House Brackmann (HB) grading system was used to assess the functional outcome of facial nerve rehabilitation. 8 patients received 50-65 Gy postoperative radiotherapy. The follow-up time ranged from 8 months to 36 months with the mean time of 12 months.Result:At all function oriented facial nerve reconstructed region, satisfactory orbicularis oculi muscle function in 7 patients was achieved (7/7); 5 patients obtained seeable and almost symmetric frowning (5/7); 9 patients obtained obvious nasolabial groove and satisfactory rest symmetry of the mouth corners (9/9); 4 patients got better facial nerve function restoration when it was 3 months after radiotherapy. Nine patients got HB grade II, and 2 patients got HB grade III facial nerve function restoration. Facial nerve electromyogram revealed weaker amplitude nerve conduction in 9 patients of HB grade II than the conduction at its corresponding normal side.Conclusion:Cable grafting of the greater auricular nerve is a feasible candidate for the immediate reconstruction of facial nerve defect. Free nerve transplantation is probably not a contraindication for postoperative radiotherapy in the parotid region. PMID- 29798374 TI - [Intratympanic steroid intervention as initial therapy for sudden sensorineural hearing loss: a systematic review of reviews]. AB - Objective:The aim of this overview is to evaluate the relevant systematic reviews and Meta-analysis that focus on intratympanic steroid intervention as initial therapy for sudden sensorineural hearing loss.Method:The literature search was based on the published systematic reviews and Meta analysis. According to the include and exclude critera, the important data was extracted. Quality assessment was rigorously performed using the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) and main outcome indicators of literature evidence quality were evaluated by Grading of Recommendations, Assessment, Development and Evaluation (GRADE).Result:Sixteen related systemic reviews and Meta-analysis (6 Chinese literatures and 10 English literatures) published during 2009-2016 were included; AMSTAR score was 4 to 9 points,14 studies was medium quality and 2 was high quality. However, the clinical evidence was controversial and there is no consensus regarding the efficacy of intratympanic steroid therapy for sudden sensorineural hearing loss.Conclusion:As an initial treatment, there is no sufficient high quality evidence to recommend the ITS therapy. There is a need for further systematic reviews that adhere to strict scientific methods. PMID- 29798375 TI - [Intratympanic dexamethasone vesus post-auricular subperiosteal injection of methylprednisolone treatment for sudden hearing loss]. AB - Objective:To compare the efficacy and side effect between intratympanic dexamethasone and subperiosteal injection of methylprednisolone treatment for sudden hearing loss.Method:One hundred and eight unilateral sudden hearing loss patients were enrolled in this study, randomly divided into A group, which was accepted intratympanic dexamethasone (10 mg/ml) , and B group, which was accepted post-auricular subperiosteal injection of methylprednisolone (40 mg/ml) by every 3 days intotal 5 times. After 3 months follow-up, analysis of the differences of pure tone threshold, tinnitus handicap inventory (THI), dizziness handicap inventory (DHI), blood glucose between pretreatment and postreatment was made. Side effect such as perforation of tympanic membrane, infection of post-auricular skin was also observed.Result:1Both in A and B group, there was no statistical changes in total efficiency and pure tone threshold decrease (P> 0.05), whereas the pure tone threshold statistical change was observed in the low frequency sudden deafness between A and B group (P< 0.05). 2Both in A and B group, there was no statistical changes in THI (P> 0.05), whereas the THI statistical decrease was observed in the high frequency sudden deafness between A and B group (P< 0.05). 3There was no statistical change in THI both in A and B group (P> 0.05). 4Both in A and B group, there was no statistical changes in fasting plasma glucose between pretreatment and postreatment (P> 0.05). 5There was no patient who had gotten tympanitis or postauricular infection, although in A group, there were 2 patients had gotten perforation of tympanic membrane, but they all healed after the follow-up.Conclusion:Both topical injection of glucocorticoid can improve pure tone threshold and reduce the score of THI and DHI for sudden hearing loss patients. Intratympanic dexamethasone can reduce more score of THI for high frequency sudden deafness patients whereas subperiosteal injection of methylprednisolone can improve pure tone threshold more for low frequency sudden deafness patients. None of the two administrations elevate blood glucose, but intratympanic dexamethasone have the risk of perforation of tympanic membrane. PMID- 29798376 TI - [Expression of intercellular adhesion molecule-1 and myeloperoxidase in peripheral blood and its significance in elderly patients with OSAHS]. AB - Objective:To investigate the detection and significance of serum intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO) in elderly patients with OSAHS in adults.Method:Ninety-three cases of elderly OSAHS patients who confirmed by PSG were observed. According to the range of AHI, they were divided into 3 groups (severe, moderate and mild). 31 cases of healthy person were observed as control group. The serum ICAM-1 and MPO were determined by ELISA method; ICAM-1 and MPO were measured after comprehensive treatment in patients with elderly severe OSAHS, and the correlation between ICAM-1, MPO and PSG were analyzed.Result:1With the severity of snoring increased, the serum levels of ICAM 1 and MPO increased gradually (F=29.937,18.946; P< 0.01); The concentration of ICAM-1 and MPO in each group showed that there was no significant difference between the mild group and the control group (P> 0.05), there were significant differences between the rest each two groups (P< 0.05). 2There was no correlation between serum levels of ICAM-1, MPO, BMI, age in OSAHS patients (P> 0.05). There was a positively relationship between ICAM-1 and MPO . Both of them were negatively correlated with AHI, and positively correlated with LSaO2 (P< 0.01). 3The concentration of ICAM-1, MPO and AHI in 31 elderly patients with severe OSAHS decreased and LSaO2 increased significantly after 3 months of comprehensive treatment (P< 0.01).Conclusion:The increase of ICAM-1 and MPO concentration in peripheral blood is one of the mechanisms of cardiovascular damage in elderly patients with OSAHS. Determination of peripheral blood ICAM-1, MPO levels in elderly patients with OSAHS to help determine the severity of disease, the evaluation of treatment,which may have a certain reference value for the prediction of cardiovascular disease risk in patients with severe OSAHS. PMID- 29798377 TI - [Analysis of related factors between portable monitoring and polysomnography]. AB - Objective:To analyze the related factors of portable monitoring and polysomnography in simultaneous monitoring of suspected OSAHS cases. To evaluate the application of portable monitoring in the diagnosis of OSAHS.Method:All patients underwent a simultaneous monitoring of both portable monitoring and polysomnography. Both the parameters of apnea hypopnea index (AHI), lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2), percentage of time with an oxygen saturation below 90%(CT90%), oxygen desaturation index (ODI), the number of apnea and hypopnea were collected and analyzed.Result:Both the portable monitoring and polysomnography showed 39 cases met the diagnostic criteria for OSAHS. Polysomnography showed 26 severe cases, 8 moderate cases and 5 mild case. Portable monitoring showed 30 severe cases, 5 moderate cases and 4 mild cases. Comparing portable monitoring with polysomnography, the parameter of AHI had a significant difference. MSaO2, LSaO2, CT90%, ODI, the number of apnea and hypopnea had no significant difference.Conclusion:Compared portable monitoring's indicators with polysomnography's indicators, both correlated well. Portable monitoring has a high diagnostic value. But the diagnostic accuracy in the severity of the disease should be improved. PMID- 29798378 TI - [Transnasal endoscopic surgery of communicating neoplasm outside cerebral dura mater and orbital fasciae]. AB - Objective:This paper is intend to observe the feasibility of surgical approach with which communicating neoplasm outside cerebral dura mater and orbital fasciae was removed by transnasal endoscopic surgery.Method:Nine patients suffered from communicating neoplasm in the area of naso-orbital-cranio complex were treated with transnasal endoscopic surgery. The size of skull base bone defect was from 1.25 cm*1.13 cm to 3.25 cm*2.69 cm. No eye enucleation was done. No reconstructions of skull base and medial wall of orbital cavity were done. Iodoform gauze was packed in paranasal sinuses fourteen days. Patients with malignant tumor were treated radiation therapy and chemical therapy after surgical treatment. The degree of resection, complications of intracranial and orbital cavities, survival condition were the focus of this study.Result:The tumor were completely removed and all operations were successfully completed by trasnasal endoscopic surgery. Only one patient was required blood transfusion due to seriously bleeding from tumor during the operation. There was no orbital, intracranial, and vascular complications. The defect of bone at skull base and lamina papyracea were automatic reconstructed. Three patients have showed recurrence of neoplasm, and two of them died during two years of following up time.Conclusion:Transnasal endoscopic surgery is a safe, reliable and effective approach to treat communicating neoplasm in the area of naso-orbital-cranio complex, of which main part of tumor exists in the sinunasal cavity. PMID- 29798379 TI - [Effects of hyperbaric oxygen on mucosal inflammatory response after nasal surgery in rabbits]. AB - Objective:To observe the effect of hyperbaric oxygen therapy for the inflammation of rabbit nasal in postoperation period, to investigate the clinical feasibility of hyperbaric oxygen therapy in reducing the inflammatory reaction and promoting mucosal healing in nasal recovery stage after surgery.Method:A total of 16 Japanese white rabbits were randomly assigned to hyperbaric oxygen group and non hyperbaric oxygen group, with 8 in each, and another 5 was divided into normal control group. The non hyperbaric oxygen group was in the normal atmospheric environment, the hyperbaric oxygen group was given hyperbaric oxygen treatment on the fifth day after the operation. All the animals were sacrificed to observe the morphological changes and pathological changes of the mucosa in the bilateral inferior turbinate surgery area at sixth weeks after operation. The normal control group was taken the same part of mucosa.Result:Specimen: hyperbaric oxygen group postoperative empyema in 2 side, 8 side of non hyperbaric oxygen group, hyperbaric oxygen group was significantly reduced compared with non hyperbaric oxygen group, the difference was statistically significant (P< 0.05). Pathological changes: in the hyperbaric oxygen group, the infiltration of inflammatory cells was mild in 12 sides and moderate in 4 sides; the non hyperbaric oxygen group was mild in 1 sides, moderate in 13 sides, and severe in 2 sides, the hyperbaric oxygen group was significantly lower than the non hyperbaric oxygen group, the difference was statistically significant (P< 0.01).Conclusion:Under the condition of this experiment, hyperbaric oxygen therapy can significantly reduce the inflammatory response of rabbit nasal mucosa after operation, and reduce the accumulation of purulent secretion. PMID- 29798380 TI - [Tympanoplasty without mastoidectomy for active otitis media]. AB - Objective:The study aims to assess the effect of tympanoplasty without mastoidectomy for the middle ear under different infected states.Method:One hundred and thirteen cases (113 ears) with chronic otitis media (COM) received tympanoplasty without mastoidectomy. All the patients were found inflammatory proliferative lesions in the mastoid and tympanic antrum via CT scan before surgery and were followed up over 1 year. The patients were placed into the infected ear group (72 ears) and uninfected ear group (41 ears) according to the infective condition. We used SPSS statistical software to analyze the efficacy.Result:Of 113 cases, 92 ears had dry ear canals in 1/2 to 1 month after surgery, and the negative air pressure in the tympanum gradually disappeared in 3 6 months after surgery. Of the 72 ears in the infected ear group, 69 ears had postoperative dry ears, and a large amount of intraoperative purulent secretion was seen in the tympanum in 4 cases, which all had dry ear canals. Three cases had relapse, for a dry ear canal rate of 95.8%. Three ears showed dry tympanic membrane perforations, and effective ears with air-bone conduction differences smaller than or equal to 20 dB accounted for 51.4% of cases. Of the 41 ears in the uninfected group, 40 ears had postoperative dry ears, 1 case had relapse, for a dry ear canal rate of 97.6%. Two ears showed dry tympanic membrane perforations. Effective ears with air-bone conduction differences smaller than or equal to 20 dB accounted for 48.8% of cases. No case of facial paralysis, dizziness, formation of invaginations of the tympanic membrane and cholesteatoma were seen in the patients included in this study during the follow-up visits.Conclusion:Whether there are inflammatory proliferative lesions in the mastoidor not, tympanoplasty without mastoidectomy is feasible for chronic active otitis media. Moreover, different infection statuses of the middle ear do not cause difference in the postoperative relapse rate and hearing improvement. PMID- 29798381 TI - [ollow-up study of otitis media with effusion in newborns and infants]. AB - Objective:To study the natural history of otitis media with effusion (OME) in infants, to guide clinical observation and treatment.Method:Newborns and infants born who failed newborn hearing screening and diagnosed OME were studied. Those with OME were diagnosed within 3 months old and followed-up. All subjects were examined with tympanometry once a month and with whole audiometric evaluation once three months. The causes, the time of recovery, and the disease course were analyzed in 46 infants followed-up at least 6 months.Result:24 infants were failed bilateral and 22 with monaural in initial hearing screening. 22 infants were failed bilateral and 24 with monaural in repeated screening. The failed ears side changed in 2 with monaural. 69 ears (bilateral in 23 cases and unilateral in 23 cases) were diagnosed OME. In these 69 ears, the 226 Hz tympanograms showed type A, type B, or type C, the 1 000 Hz tympanograms had no peak, the distortion product otoacoustic emission (DPOAE) were not found, the response thresholds of auditory brainstem response (ABR) were 20-60 dBnHL. 37 cases (80.4%) were recovered, and 9 cases were unrecovered. The first recovered case was in 4 months old, the last one was in 18 months old. 29 recovered cases were followed-up less than 6 months (with 9 months old), 7 cases in the 9 unrecovered cases did not return visit after followed-up 6 months, but they were found that the hearing level improved by the telephone follow-up. The other 2 cases showed recurrence and from unilateral ear to both ears. The causes included choking milk, rhinobyon, and cold repeatedly.Conclusion:OME in infants has the self-healing nature. We suggest to observe the infants for a long time. Avoiding the causes is benefit to self-healing. PMID- 29798382 TI - [Application of oto-endoscope on intact canal wall mastoidectomy]. PMID- 29798383 TI - [Diagnosis, misdiagnosis, and treatment of facial nerve Schwannoma (7 cases report)]. PMID- 29798384 TI - [Transoral resection of partial fistula wall to treat incomplete second branchial fistula: a case report]. AB - We describe a case of a 55-year-old man who presented with sore throat for two days, while neck swelling for one day, and was found to have a fistula in his left tonsil and an abscess in his left lateral pharyngeal wall with the lower bound to the upper border of the cricoid cartilage by ultrasonography and enhanced CT. The fistula from tonsillar fossa to hypopharynx was detected followed by left tonsillectomy, and then anterior wall of the fistula and mucosa covering it was resected. He was eventually diagnosed with incomplete second branchial fistula with infection, and was followed up for five years with no recurrence. PMID- 29798385 TI - [Primary malignant tumor of uvula: report of 3 cases and review of the literature]. AB - We retrospectively analyzed 3 middle-aged male patients of primary malignant tumor of uvula. There was a long history of smoking and drinking for the patients. All of them came to the hospital with the syptoms of pharyngeal foreign body sensation and two of them had pharyngeal sore. The patients appeared well, new neoplasm at the apex of the uvula. Diameter of 2 cases were less than 1 cm without invading the midline of the soft palate. Another patient's diameter was more than 1 cm with invading the midline of the soft palate. Preoperative pathology diagnosis of 3 patients was squamous cell carcinoma of uvula. The pharyngeal CT of the patient with invading the midline of the soft palate showed nodules at the end of the soft palate, obviously enhancement and small lymph node in left neck. PMID- 29798386 TI - [Progress in multi-omic study of head and neck cancer]. PMID- 29798387 TI - [The related factors of head and neck mocosal melanoma with lymph node metastasis]. AB - Objective:To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method:A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1?3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P<0.05 difference was statistically significant. Result:The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence (P=0.0000), bone invasion (P=0.001), primary position (P=0.007). Recurrence (P=0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion (P=0.487) and primary location (P=0.367) remained to be further explored. Conclusion:The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment. PMID- 29798388 TI - [The effect of regional neck dissection on positive cervical lymph node of cN0 laryngeal carcinoma]. AB - Objective:To evaluate the efficacy and safety of regional neck dissection in the treatment of cN0 laryngeal carcinoma with positive cervical lymph node. Method:A retrospective analysis of 120 cases with cN0 laryngeal squamous cell carcinoma who received the first time for primary tumor resection and regional neck dissection (II-IV) in our hospital during the period of 2000.01-2016.06 were performed. Twenty-two patients with lymph node positive (pN+) were selected by postoperative paraffin pathology in II-IV region and followed up to 2017.06. The recurrence rate, survival rate and survival related regression analysis of patients with stage cN0 pN+ laryngeal carcinoma were analyzed. Result:The cN0 laryngeal cancer occult metastasis rate was 18.33% (22/120) in regional neck dissection. Local recurrence, regional recurrence, distant metastasis rates of 3 and 5 years were 41.18%, 17.65%, 17.65% and 40.00%, 13.33%, 20.00%, respectively in cN0 pN+ patients. The overall survival rates of 3 and 5 years were 61.2% and 30.6% respectively, and the disease-free survival rate was 31.8% and 22.7%. There was no significant difference in overall and disease-free survival between the T staging or clinical classification (P>0.05). Cox regression analysis showed that overall survival was related to age and local-regional (RR=11.421, P=0.001, RR=5.211, P=0.022). Logistic multivariate regression analysis showed that local regional recurrence was not related to each factor (P>0.05). Conclusion:Local recurrence rate and mortality rate of cN0 pN+ laryngeal carcinoma are higher, survival rate is lower, however, neck recurrence rate is low.Therefore, II-IV neck dissection is a safe and effective treatment for neck of cN0 pN+ laryngeal carcinoma. PMID- 29798389 TI - [Clinical analysis of neuroendocrine carcinoma of the larynx]. AB - Objective:To evaluate the clinical manifestation, therapy and prognosis of neuroendocrine carcinoma of the larynx. Method:Twenty-six cases with neuroendocrine carcinoma of the larynx were analyzed retrospectively. Four pathological types were found in our series: typical carcinoid (1/26), atypical carcinoid (15/26), small cell carcinoma, neuroendocrine type (9/26) and combined small cell carcinoma, neuroendocrine type (1/26). In this series, 12 cases were received total laryngectomy, 2 cases supracricoid partial laryngectomy cricohyoidopexy (SCPL-CHP), 4 cases horizontal partial laryngectomy, 5 cases vertical partial laryngectomy, 1 case transoral CO2 laser microsurgery, and 2 cases radiotherapy and/or chemotherapy. Result:Three-year and five-year overall survival rates were 76.9% and 69.2% respectively. Conclusion:The neuroendocrine carcinoma of the larynx was rare, which was more common in the supraglottis. Atypical carcinoid was the most common pathological type. Compared to SCC, the clinical feature of neuroendocrine carcinoma of the larynx was non-specific. The clinical behavior, treatment,and prognosis were correlative to the tumor pathological.The diagnosis depended on comprehensive immunohistochemistry examination. PMID- 29798390 TI - [Platysma myocutaneous flaps in reconstruction of defects caused by hypopharyngeal cancer resection]. AB - Objective:To study the method and feasibility in reconstruction of platysma myocutaneous flap of defects caused by hypopharyngeal cancer resection. Method:Twelve cases underwent reconstruction with the platysma myocutaneous flap of hypopharyngeal soft defect were investigated. All cases received 2 times preoperative induction chemotherapy followed by hypopharyngeal cancer resection with laryngeal function preservation and the neck lymph node dissection. Platysma myocutaneous flap was used to repair the hypopharyngeal soft tissue defect. Result:All the flaps survived. Three weeks after surgery, all patients can eat without pharyngeal fistula and dysphagia, but pharyngeal foreign body sensation. Three cases of cough after surgery, improved after training. After postoperative radiotherapy, flap survived without secondary necrosis. Laryngeal function of all cases was retained, and only one case with cannula maintained. Conclusion:Preoperative induction program can effectively reduce the lesion. The placenta myocutaneous flap has rich blood supply, strong anti-infectivity. It is an effective method to repair the hypopharyngeal tissue defect with the placenta myocutaneous flap. PMID- 29798391 TI - [Association of vitamin D receptor and its genetic polymorphisms with nasopharyngeal carcinoma]. AB - Objective:To investigate the gene expression and polymorphisms of vitamin D receptor (VDR) in nasopharyngeal carcinoma. Method:The expression of VDR mRNA was detected by fluorescent quantitative PCR in PBMC from 48 patients with nasopharyngeal carcinoma and 48 controls. The FokI and ApaI loci of all subjects were detected by TaqMan-MGB fluorescent probe PCR. Result:The VDR mRNA ?Ct value was 9.32+/-0.91 and 7.31+/-1.04 in nasopharyngeal carcinoma patients and controls, respectively. Using multivariate Logistic regression analysis, the results showed that the distribution of FokI point Ff genotype in the case group was significantly higher than that in the control group (adjusted OR=1.97, 95%CI=1.33-2.91). No difference was found between the control group and the patient group at ApaI loci. Further haplotype analysis was used to find that compared with fa haplotypes, the distribution of FokI Ff genotype in the case group was significantly higher than that in the healthy control group (adjusted OR=0.65, 95%CI=0.48-0.87). There were significant differences in the gene expression level of VDR among the patients with the different genotypes of FokI loci (F=194.5, P<0.01). Conclusion:Genetic variants of the VDR gene are closely associated with nasopharyngeal carcinoma. PMID- 29798392 TI - [Preoperative airway management and perioperative period asphyxia prevention in patients with tumors invasion in the cervical tracheal]. AB - Objective:To investigate the effect of preoperative airway treatment and postoperative asphyxiation preventive measures in patients with tumors invasion in the cervical tracheal. Method:The clinical date of 35 patients with different degree of tumors invasion in the cervical tracheal were analyzed retrospectively. Anesthesia including normal endotracheal intubation anesthesia, awake intubation anesthesia with visual laryngoscope assisted after topical anesthesia, intubation anesthesia with preoperative tracheotomy, intubation anesthesia after transection of trachea and anesthesia with extracoporeal circulation was selected according to the patient's situation such as whether exist forced position, or the extent of dyspnea, or the range of recurrent tumor. Preventive tracheotomy or fistulization was performed according to the patients' tracheal involvement and the choice of operation and general condition during the operation. Result:All 35 patients were successfully anesthetized, 17 of whom had no dyspnea or forced position, this kind patients were all anesthesia successfully, and 3 of them underwent prophylactic tracheotomy. Sixteen cases of nonrecurrent tumor with forced position, 15 patients were accepted awake anesthesia successfully with visual laryngoscope assisted after topical anesthesia, 1 patient who cannot be intubated or done tracheotomy is completed with extracorporeal circulation; prophylactic tracheotomy or tracheostomy was performed in this group. Of 2 cases of recurrent tumor with forced posture, preoperative tracheal intubation failed, 1 case was intubated after emergency transection of trachea, 1 case was successfully intubated by emergency tracheotomy before operation and 2 cases received postoperative tracheostomy. In this study, no serious complications such as massive bleeding, asphyxia and cardiovascular accident occurred after the operation. Conclusion:The preoperative airway management of patients whose tumors involves the cervical tracheal and whether tracheotomy or ostomy need to prevent asphyxia or not should be based on the nature of the tumor such as whether is recurrent, the extent of trachea involvement and whether to merge the OSAHS. Only by considering the various factors that affect the airway synthetically, an effective method can be adopted to ensure the safety of the operation. PMID- 29798393 TI - [Effects of adenotonsillectomy on immunoregulation in children with obstructive sleep apnea hypopnea syndrome]. AB - Objective:To observe the effects of adenotonsillectomy on immunoregulation in children with obstructive sleep apnea hypopnea syndrome. Method:Thirty-six OSAHS children were recruited as an experimental group while 40 healthy children for the control group. Blood samples were collected from experimental group and control group. Tonsillectomy and adenoidectomy were performed under general anesthesia in the experimental group. Blood samples of the experimental group were collected at 4 days, 1, 3 and 6 months after operation, respectively. Lymphocyte subsets, NK cells and immunoglobulin were analysis in all patients. Result:1The expression of IgA in the experimental group was significantly lower than the control group before operation (P<0.01). No significant difference was found between the other groups (P>0.05). 2The percentage of CD4+ T cells and CD4+/CD8+ ratio in the experimental group were significantly lower than those in the control group before operation (P<0.01 or <0.05). The percentage of CD8+ T cells in experimental group was significantly higher than that in control group one day before operation (P<0.01). 3In the experimental group, the expression of IgG at 4 days and 1 month was significantly lower than that before operation (P<0.05). At 3 and 6 months after operation, IgA was significantly higher than that before operation, the difference was statistically significant (P<0.01 or <0.05). No significant difference was found between the other groups (P>0.05). 4The percentage of CD4+ T, CD3+ T and NK cells, CD4+/CD8+ ratio in the experimental group at post-operative 4 days were lower than those before operation, and the percentage of CD8+ T cells was CD4+/CD8+ ratio in 3 and 6 months after operation was higher than that before operation, and CD8+ T was lower than before operation,the difference was statistically significant (P<0.01 or <0.05). No significant difference was found between the other groups (P>0.05). Conclusion:1Compared with healthy children, OSAHS children have a certain degree of cellular and humoral immune disorders, accompanied by different levels of cellular and humoral immune function decline. 2The cellular and humoral immune function in children with obstructive sleep apnea hypopnea syndrome (OSAHS) decreased within 1 month, but recovered to healthy children at 6 months after operation. Adenoidectomy and tonsillectomy were helpful to restore the immune function of children with OSAHS. PMID- 29798394 TI - [The clinical anatomy of the inferior thyroid arteries and veins and the safety of the modified tracheotomy]. AB - Objective:To evaluated the clinical anatomy of the inferior thyroid arteries and veins and the safety of clinical application of the modified tracheotomy. Method:Sixty patients who need partial resection or full resection of thyroid cancer and 50 patients with laryngeal or hypopharyngeal cancer required tracheotomy were enrolled in this study. The distribution of the inferior thyroid arteries and veins closely related to tracheotomy is further dissected. The inverted "U" type of tracheal flap tracheotomy was further improved based on anatomical findings. Finally, the further modified tracheotomy was used for clinical practice and compared with the conventional tracheotomy and the inverted "U" type of tracheal flap tracheotomy. Result:Of the 110 cases, the lowest thyroid artery was found in 11 cases, with a rate of 10%. The inferior thyroid vein has 2-4 branches, which originates from the lower lobe or isthmus of the thyroid lateral lobe, descending in the anterior tracheal space. According to the characteristics of the static reflux of the thyroid gland, the lower thyroid vessels are classified into four types: intravenous dry type (28 cases); intravenous double dry without traffic type (43 cases); intravenous double trunk with traffic (28 cases); mixed type (11 cases). At present, the further modified tracheotomy can effectively avoid the rebleeding of the lower thyroid arteries and veins. There were no bleeding and other complications in all cases. Conclusion:It provides a basis for the further modified of tracheotomy based on the clinical anatomy of the inferior thyroid artery and vein, which is closely related to tracheotomy. The further modified tracheotomy has certain advantages than the conventional tracheotomy and the inverted "U" type of tracheal flap tracheotomy. PMID- 29798395 TI - [An analysis of spectrum of allergen sensitization among patients with tree pollen allergy in Beijing]. AB - Objective:To explore the feature of allergic sensitization of tree pollen and the relationship between tree pollen and airborne pollen in Beijing. Method:Two thousand five hundred and twenty-one patients with allergic diseases were enrolled between January to July in 2017 in an allergy department. All patients received SPT of 8 kinds of tree pollen. Result:1The overall tree pollen positive rate of SPT was 49.3% (1 244/2 521). Male had a higher positive rate than female (56.4% vs 45.0%, P<0.01) while child group had a higher positive rate than adult group (55.9% vs 48.6%, P<0.05). The poly sensitization was observed with a rate of 26.3%, take the percentage of 53.3% of the overall positive subjects. 2The highest sensitization rate was found in March (62.2%), followed by May (52.1%), the lowest was January (27.9%). There was a positive correlation between tree pollen sensitization rate and pollen count of each month (r=0.929, P<0.01). 3Cypress had the highest positive rate (34.6%), followed by poplar (21.3%), the lowest was sophora (13.3%). The sensitization rate was positively correlated with pollen count among different tree pollen (r=0.714, P<0.05). Conclusion:The main allergic pollen in Beijing was cypress. The tree pollen sensitization showed a seasonality with the peak in March. The sensitization status was tightly associated with the amount of airborne pollen. PMID- 29798396 TI - [Imaging charateristics of bony erosion and fungal culture analysis in allergic fungal rhinosinusitis]. AB - Objective:To investigate the imaging characteristics of bony erosion, fungal culture and related factors in allergic fungal rhinosinusitis (AFRS). Method:Sixty cases of AFRS were reviewed in this study. The characteristics of Computed Tomography and Magnetic Resonance Imaging including positive rate of bony erosion, eroded sites, disease extension and sinus expansion were summarized. Fungal culture and identification of nasal secretion were done. The correlation between the degree of sinus expansion, species of fungi and bony erosion was evaluated by statistical analysis. Result:Of the 60 patients, 18 (30%) had bony erosion. There was a significant difference in the proportion of bone erosion among the sinuses (P<0.05). The most commonly eroded site was the ethmoid sinus. The orbit were the most common adjacent anatomic spaces to exhibit disease extension, and anterior cranial fossa is the second most common. Statistical analysis revealed a significant association(P<0.05)of bone erosion with sinus expansion. The positive rate of fungal culture was 51.3%, among which the most common is Aspergillus. Statistical analysis shows no association(P>0.05)of bone erosion with specific fungi. Conclusion:Bone erosion is an important imaging feature of AFRS. Bone erosion may cause by sinus expansion. Extension of disease into the orbit or intracranial cavity results from a natural progression of disease after erosion occurs. Specific fungal species that can cause bone erosion was found. PMID- 29798397 TI - [A preliminary study on the relationship between laryngopharyngeal reflux and chronic rhinosinusitis]. AB - Objective:To study the relationship between laryngopharyngeal reflux and chronic rhinosinusitis. Method:A total of 46 patients were enrolled in this study including 25 cases with chronic rhinosinusitis with nasal polyps, 10 cases with chronic rhinosinusitis without nasal polyps and 11 cases underwent surgery due to abnormal nasal anatomy such as nasal septum deviation, bubble in the turbinate, etc. as control group. The expression of pepsin was detected using immunohistochemistry in three groups. The intensity of pepsin expression and CT score of sinus, blood eosinophils percentage, blood neutrophils percentage, blood basohils percentage, blood mononuclear percentage, blood lymphocytes percentage were analyzed. Result:There were 8 strong positive cases (32%, 8/25), positive in 8 cases (32%, 8/25), 2 weakly positive cases (8%,2/25), 7 negative cases (28%, 7/25) in chronic rhinosinusitis with nasal polyps group. In the chronic rhinosinusitis without nasal polyps group, the expression of pepsin was strong positive in 4 cases (40%, 4/10), positive in 3 cases (30%, 3/10), weakly positive in 1 cases (10%, 1/10), negative in 2 cases (20%, 2/10). There were no strong positive expression in the control group, positive in 2 cases (18.2%, 2/11), weakly positive in 3 cases (27.3%, 3/11), negative in 6 cases (54.5%, 6/11), chronic rhinosinusitis with nasal polyps group and chronic rhinosinusitis without nasal polyps group higher than the control group (P<0.05). There was no significant difference in pepsin expression between chronic rhinosinusitis with nasal polyps group and without group (P=0.617). Spearman correlation analysis indicated that the intensity of pepsin was positively correlated with the score of Lund-Markay (r=0.349,P=0.017),? there was no correlation with the percentage of various inflammatory cells. Conclusion:The positive expression intensity of pepsin in chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps is significantly higher than that in normal control group, suggested that there is a correlation between laryngopharyngeal reflux and chronic rhinosinusitis. Laryngopharyngeal reflux is positively correlated with the severity of nasal polyps. Chronic nasal inflammation caused by laryngopharyngeal reflux is not mediated by a certain kind of inflammatory cells. PMID- 29798398 TI - [Diagnostic value of magnetic resonance imaging for middle ear cholesteatoma: a Meta-analysis]. AB - Objective:To evaluate the values of magnetic resonance (MR) in the diagnosis of middle ear cholesteatoma by meta-analysis. Method:The articles concerning the diagnosis of middle ear cholesteatoma by using MRI until September 2017 were searched in databases including The Cochrane Library, PubMed, CBM, VIP, Wan Fang Data and CNKI with the search term "cholesteatoma, MR, Magnetic Resonance". Two independent researchers screened literature, extracted data, and assessed the risk of the bias of included studies with the inclusion and exclusion criteria using the QUADAS-2 tool. Then, meta-analysis was performed using Stata 12.0 software. The pooled weighted sensitivity and specificity were calculated, the summary receiver operating characteristic curve (SROC) was drawn and the area under the curve was calculated. Result:A total of 21 original studies were included. The results of meta-analysis showed that the pooled sensitivity, specificity, DOR and area under SROC curve of MR for diagnosing middle ear cholesteatoma were 0.88 (95%CI0.83 to 0.92), 0.91 (95%CI0.86 to 0.95), 10.13 (95%CI6.20 to 15.55), 0.13 (95%CI0.09 to 0.19), 79.23 (95%CI37.74 to 166.33), and 0.96 (95%CI0.93 to 0.97), respectively. The 1.5T MR has little differences with 1.5T MR in diagnosing middle ear cholesteatoma. In contrast to retrospective studies, prospective studies have further demonstrated that MR has a higher diagnostic value for middle ear cholesteatoma. Based on regions, the analysis showed that MR in Europe was more valuable in the diagnosis of middle ear cholesteatoma. Conclusion:In the diagnosis of middle ear cholesteatoma, MR has a high value. PMID- 29798400 TI - [Application of the microdissection needle for endoscopic prelacrimal recess approach]. PMID- 29798399 TI - [Investigation of epithelial-mesenchymal transition induced by cisplatin on human laryngeal resistant cancer cells]. AB - Objective:To investigate the mechanism between epithelial-mesenchymal transition (EMT) and cisplatin induced resistant cell subline and the malignant biological characteristics, to explore EMT in human hep-2 laryngeal resistant cells. Method:Using cisplatin-resistant cells (hep-2/CDDP) and non-resistant cells (hep 2) established in our previous study; the invasion and migration biological behaviors were detected by transwell and scratch assay; the expressions of E cadherin, Zo-1, Snail, Slug, Twist1, Vimentinon in the mRNA level were detected by RT-qPCR and the protein level by Western blot. Result:Transwell and scratch assay show the invasion and migration behaviors were increased in hep-2/CDDP cells (P<0.05), the epithelial marker E-cadherin and Zo-1 were downregulated in hep-2/CDDP cells (all P<0.05), transcription factor Snail, Slug were upregulated in mRNA and protein level (all P<0.01) while Twist1 had no significant changed in protein level (P>0.05), the expression of mesenchymal marker Vimentin was also increased in mRNA and protein levels in cisplatin resistant cells (P<0.01). It was confirmed that the hep-2/CDDP cells possessed EMT phenotypes. Conclusion:The cisplatin resistant laryngeal cancer cells perform higherinvasion and migration biological behaviors,and the mechanisms of increased ability of invasion and migration induced by cisplatin was associated to eEMT, study on signal path related to EMT may overcome cisplatin resistance and reduce invasion and migration behaviors. PMID- 29798401 TI - [Endoscopic assisted minimally invasive cochlear implants: a review of 40 cases]. PMID- 29798402 TI - [Nasal glioma in sphenoid sinus: a case report and literature review]. AB - Nasal glioma is a rare congenital malformation in maxillofacial region. It is sluggish, benign, non-tumorous and with low recurrence rate. It is important to evaluate whether there is any intracranial connection before the operation through CT or MRI to avoid the serious intracranial complications. We reported a case of a adult with a nasal glioma in sphenoid sinus, and discuss clinical characteristics, diagnosis, and pathology. PMID- 29798403 TI - [Hodgkin's lymphoma of salivary gland: a case report]. AB - Hodgkins lymphoma (HL) of salivary gland is extremely rare. We reported a bilateral HL in a female of 58 years old, whose main clinical complaint was bilateral enlargement of parotid gland and cervical lymph nodes. The clinical symptoms were relieved after intermittent treatment by anti-inflammatory drugs and traditional Chinese herbs resulted in misdiagnosis of chronic lymphadnitis. The postoperative pathological diagnosis was HL of parotid gland, submandibular gland and cervical lymph nodes. It implies that lymphoma shall also be take into consideration even if anti-inflammatory drugs and Chinese traditional herbs have treatment effect on a parotid gland mass. PMID- 29798404 TI - [The clinical application status and progression of auditory steady-state evoked response]. AB - Auditory steady-state evoked response(ASSR) is an objective method to evaluate hearing threshold. Recently, it was reported that CE-Chirp ASSR is more reliable than the conventional ASSR in predicting the behavioral hearing threshold. Many reseaches were conducted to improve the reliability of ASSR threshold and behavioral threshold. This paper reviewed the development, principle, clinical application status, and progress of ASSR. PMID- 29798405 TI - [Current treatment of pharyngocutaneous fistula after total laryngectomy]. AB - Pharyngocutaneous fistula is a common and serious complication after total laryngectomy, and it will seriously affect patients' postoperative recovery. The treatment of pharyngeal fistula mainly include conservative and surgery therapy. The use of negative-pressure wound therapy and endoscopic technique to treat post laryngectomy pharyngocutaneous fistula also acquire good result in recent years. However, specific therapy options should be choose according to the type and size of the fistula, the patient's overall health condition and preoperative chemoradiotherapy etc. This article will give a review on the status of treatment of pharyngocutaneous fistula after total laryngectomy. PMID- 29798406 TI - [Advance in research of delayed endolymphatic hydrops]. AB - Delayed endolymphatic hydrops (DEH) is a disease entity first described by Kamei and named by Schuknecht, defined as profound sensorineural deafness at early stage and after several years started to appear clinical feature of endolymphatic hydrops such as vertigo, aural fullness like Meniere's disease or fluctuating hearing loss in the contralateral ear . DEH can be classified into ipsilateral type, contralateral type and bilateral type. Although DEH has low incident rate, there are many kinds of etiology and audiology and vestibular tests. Up to now, a lot of literatures about etiology, diagnose, clinical manifestation, relevant examination and therapy of DEH were published abroad. In this review, we will make a summary of research status of DEH. PMID- 29798408 TI - [Retrospective study of partial superficial parotidectomy and superficial parotidectomy on superficial parotid benign tumor]. AB - Objective:To compare the clinical effect between partial superficial parotidectomy (PSP) and superficial parotidectomy (SP) through a retrospective analysis and to provide evidence for the benign tumor surgical strategy. Method:According to different surgical strategies performed, 168 patients with superficial parotid benign tumor were reviewed and divided into PSP group and SP group. Clinical data was compared between two groups from different aspects, including operation condition, complications, recurrence rate, as well as parotid function. SPSS 22.0 software was used in statistical analysis. Result:PSP group has an average operative incision length of (6.65+/-1.17)cm, and average operation time of (82.25+/-11.56)min, while SP group is (10.86+/-1.65)cm and (121.42+/-17.32)min. So, compared with the SP group, PSP has obvious advantages in operation conditions (P<0.01). Furthermore, PSP group also presents an advantage over SP group in occurrence of postoperative complications (P<0.05), while there is no significant difference between two groups in palindromia rate (P>0.05). As for the maintenance of parotid gland functions, PSP group could retain most of parotid functions, but no function would be retained in SP group. Statistical analysis confirms the significance (P<0.05). Conclusion: Compared with SP, in PSP there is declined complication incidence but no increased palindromia recurrence. However, PSP has an apparent advantage on decreased surgical incision length, downscaled operation scope, reduced operation time and retained original functions of gland. All these advantages present the reliability and feasibility of PSP in treating superficial parotid benign tumor. PMID- 29798407 TI - [Curative effect analysis of the vestibular rehabilitation training on residual dizziness after successful canalith repositioning maneuvers in patients with benign paroxysmal positional vertigo]. AB - Objective:To explore the curative effect and quality life of the vestibular rehabilitation training on residual dizziness after successful canalith repositioning maneuvers in patients with benign paroxysmal positional vertigo (BPPV). Method:Residual dizziness after successful canalith repositioning maneuvers in patients with BPPV were enrolled in our study. They were randomized into three groups, the control group A were no disposition which include 32 patients, the intervention group B were guided to self rehabilitation training which include 33 patients, the control group C were guided to Brandt Daroff training which include 33 patients. Dizziness handicap inventory (DHI) and residual dizziness duration were used to evaluation the patients. Result:After one week vestibular rehabilitation training, the scores of DHI in group B and C decreased, and there was no significant difference (P>0.05), there were significant differences between group B and group C in group A, respectively (P<0.01). After four weeks of vestibular rehabilitation training, the scores of DHI in group B and group C were lower than those in group A, the decrease of group B was significantly higher than that of group C (P<0.01). The residual dizziness duration indicated that no statistical differences in the B, C groups (P>0.05) and scores of group B,C were significantly lower than group A (P<0.05). Conclusion:The appropriate vestibular rehabilitation training on residual dizziness after successful canalith repositioning maneuvers in patients with BPPV can help promote the central vestibular compensation, reduce the residual symptoms, improve the quality life of patients, and which can be used as the adjuvant treatment on BPPV patient who has residual dizziness symptoms. PMID- 29798409 TI - [The fMRI research of vestibular migraine neural pathways]. AB - Objective:To investigate the abnormal functional response of neural pathways of vestibular migraine (VM) patients, located the functional area, and inferred the possible mechanism. Method:Twenty patients of VM, 20 of migraine without aura (MwoA), and 20 of healthy controls (HC), underwent whole-brain blood oxygen level dependent (BOLD) fMRI during ear irrigation with cold water. We chose the stimulation image and the diapause stimulation image. Analyses explored functional area with BOLD signal change of the three groups. Result:We observed task-positive BOLD signal change in cortical and subcortical pattern in response to ear irrigation of all participants. Such as parietal lobe, temporal lobe, insular lobe, cingulate gyrus, thalamus, caudate nucleus, optic radiation, precuneus. VM patients showed a significantly task-negative in thalamic and fusiform gyrus in comparison with the other groups (P<0.05). Conclusion:fMRI could response the respective functional area objectively. We inferred the possible mechanism of VM was abnormal activation of thalamus and fusiform gyrus, produced crossing between the vestibular sensory pathway conduction and the pain conduction. PMID- 29798410 TI - [Analysis of the speech discrimination scores of patients with congenital unilateral microtia and external auditory canal atresia in noise]. AB - Objective:Case-control study analysis of the speech discrimination of unilateral microtia and external auditory canal atresia patients with normal hearing subjects in quiet and noisy environment. To understand the speech recognition results of patients with unilateral external auditory canal atresia and provide scientific basis for clinical early intervention. Method:Twenty patients with unilateral congenital microtia malformation combined external auditory canal atresia, 20 age matched normal subjects as control group. All subjects used Mandarin speech audiometry material, to test the speech discrimination scores (SDS) in quiet and noisy environment in sound field. Result:There's no significant difference of speech discrimination scores under the condition of quiet between two groups. There's a statistically significant difference when the speech signal in the affected side and noise in the nomalside (single syllable, double syllable, statements; S/N=0 and S/N=-10) (P<0.05). There's no significant difference of speech discrimination scores when the speech signal in the nomalside and noise in the affected side. There's a statistically significant difference in condition of the signal and noise in the same side when used one syllable word recognition (S/N=0 and S/N=-5) (P<0.05), while double syllable word and statement has no statistically significant difference (P>0.05). Conclusion:The speech discrimination scores of unilateral congenital microtia malformation patients with external auditory canal atresia under the condition of noise is lower than the normal subjects. PMID- 29798411 TI - [Expression of Fra-1 in laryngeal squamous cell carcinoma]. AB - Objective:To investigate expressions of Fra-1 in laryngeal squamous cell carcinoma. Method:Using immunohistochemical method and RT-PCR detecting 47 cases of laryngeal squamous carcinoma tissues and 21 cases of para-carcinoma tissues with the level of protein and mRNA, we analyzed the relationship of the genes expression and clinical parameters. Result:The level of protein positive expression of Fra-1 genes in laryngeal squamous cancer tissue were higher than adiacent tissues (P<0.05). The expression of Fra-1 protein in laryngeal squamous cancer tissue were significant correlation with the clinical stages, lymph metastasis, smoking. They had no significant correlation with the pathological grade, age, anatomic zonation. The mRNA level expression of Fra-1 genes in laryngeal squamous cancer tissue were higher than adjacent tissues (P<0.01). The expression of Fra-1 gene in the mRNA level was correlated with pathologic stage, clinical stage, lymph metastasis, and smoking, but wasn't correlated with age and anatomic zonation. Conclusion:In laryngeal squamous cell carcinoma, the expression of Fra-1 gene are overexpressed. Fra-1 may play a role in the occurrence and development of the laryngeal cancer. PMID- 29798413 TI - [Study on the serum 25-hydroxyvitamin D levels of benign paroxysmal positional vertigo patients]. AB - Objective:To study whether serum 25-hydroxy vitamin D can be used as an independent indicator of prognosis in patients with benign paroxysmal positional vertigo. Method:Two hundred and two patients with BPPV were collected and divided into vitamin D deficiency group and control group according to their serum 25-OHD level. The severity of the symptoms and the recurrence rate were compared between the two groups. Result:Compared with the control group, patients with vitamin D deficiency group showed severer symptoms, either in longer duration of vertigo, lower success rate of repositioning maneuver treatment at the first time, or higher recurrence rate within six months. Conclusion:Serum 25-OHD level was negatively correlated with the severity and prognosis of BPPV, and could be used as an important index to evaluate the prognosis of BPPV. PMID- 29798412 TI - [Comparative study of VOTE classification in obstructive sleep apnea hypopnea syndrome patients between awake and sleep state]. AB - Objective:To compare the differences of the sites of airway obstruction in OSAHS patients between awake and sleep state by using the VOTE classification system. Method:Forty OSAHS patients diagnosed by PSG underwent awake Muller's maneuver and drug-induced sleep endoscopy (DISE). Video and compare the observation. Its findings were described using the VOTE classification system which include the following features: level, degree and configuration of obstruction. Associations were analyzed between different degrees of obstruction, BMI, AHI, minimal SaO2 and average SaO2. Result:Our patients had 52.5% complete velum collapse and 30.0% complete oropharyngeal lateral wall collapse in awake Muller's maneuver. In DISE, airway closure of 95.0% cases related to velum occurred collapse in concentric configuration, and 90.0% cases showed completely obstructive. We found that 60.0% complete oropharyngeal lateral wall collapse and 17.5% complete tongue base collapse. There was a significant difference in the VOTE scores between DISE and awake Muller's maneuver, and the VOTE scores of DISE were higher in all levels (P<0.05). No association was found between degrees of obstruction, AHI, BMI, minimal SaO2 and average SaO2 in Muller's maneuver (P>0.05). Complete velum collapse was just significantly associated with AHI and minimal SaO2 in DISE (P<0.05). Conclusion:The VOTE scores of DISE were higher than awake Muller's maneuver, reflected by more obstructive levels and severe degree. The difference between different degrees of obstruction, BMI, AHI, minimal SaO2 and average SaO2 was not significant. PMID- 29798414 TI - [The expression and clinical significance of survivin in salivary gland adenoid cystic carcinoma: a Meta analysis]. AB - Objective:This Meta-analysis was performed to explore the association between survivin expression and clinical pathological features of salivary gland adenoid cystic carcinoma (SACC). Method:Literature was searched in some databases such as PubMed, Embase, Cochrane Library, web of science, OVID, Springerlink, CNKI, CBM, Wanfang and CQVIP. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated to determine the correlation between survivin expression and SACC using a fixed or random effects model according to heterogeneity. Result:A total of ten studies with 367 SACC patients and 124 normal control subjects were included in this Meta-analysis. The results showed that survivin was overexpressed in SACC tissues (OR=38.26, 95% CI: 17.37-84.29, P<0.01). It also revealed significant correlations between survivin expression and pathological types (OR=0.3, 95% CI: 0.17-0.55, P<0.01), advanced tumor clinical stages (OR=0.23, 95% CI: 0.13-0.42, P<0.01) and lymph node metastasis (OR=3.7, 95% CI: 1.82-7.56, P<0.01). Conclusion:The current study demonstrated that survivin expression may be associated with the clinical pathological features of SACC. However, due to the influence of the quantity and quality of the included literature, additional high quality of studies with larger sample sizes are needed to confirm our findings. PMID- 29798415 TI - [Degeneration and regeneration characteristics of nerves and muscles after recurrent laryngeal nerve injury]. AB - Objective:We investigated the degeneration and regeneration characteristics of nerves and muscles after different degrees of recurrent laryngeal nerve (RLN) injury, and then discussed the possible relations between them. Method:Ninety five Sprague Dawley (SD) rats were used in this study, 2 rats died of infection, 2 died during surgery and 1 died in transit. The rest 90 SD rats were classified as having complete injuries (transection,43 rats), incomplete injuries (crush, 43 rats) and conrtol group (4 rats). The characteristics of nerve injuries were evaluated by endoscopic examination, laryngeal electromyography (LEMG), and histopathologic examination at 6 hours, 12 hours, 1 day, 3 day, 5 day, 1 week, 2 weeks, 3 weeks and 4 weeks after the injury. Result:All the vocal folds kept fixation in the completely injury group, where as 41/43 vocal folds in imcompletely injury group got normal activity 2 weeks after surgery, 1 at 3 weeks and 1 at 4 weeks. Fibrillation potentials were found 1 day after transection, and rennervation potentials appeared 4 weeks after transection. LEMG was normal 3 weeks after RLN was crushed. The average muscle fiber number of the left thyroarytenoid (TA) decreased with the time in the completely injury group, which increased in the second week after crush. Degeneration appeared more seriously in the distal region after transaction, and a small amount of large myelinated nerve fibers appeared at 4 weeks after injury. The most serious nerve degeneration appeared in the first day after crush, and 1 week later the ultrastructures of RLN were almost normal. The phagocytosis of Schwann cells occurred within 2 weeks after injury, 3 weeks later we found the apperance of Schwann cells who did not wrap around nerve fibers, especially in the proximal region. In the crush group, the phagocytosis of Schwann cells occurred within 1 week after injury, apoptosis and degeneration appered occasionally. Inflammatory response was more severe in the transection group, the number of fibroblasts and collagen fibers in the mesenchy increased. Conclusion:The degeneration is more severe in the distal nerve when RLN is traversed. Nerve regeneration appears in the fourth week after RLN is traversed. Injuried nerve has the ability to repair itself. Schwann cells play a role in phagocytosis after injury, and immature Schwann cells are found. Nerve fiber disintegration product can accelerate the migration of macrophage activation. PMID- 29798416 TI - [Metformin induced apoptosis of papillary thyroid carcinoma BCPAP cells]. AB - Objective:To investigate the role of metformin in inducing apoptosis of papillary thyroid carcinoma BCPAP cells. Method:Using MTT methods to detect effects of metformin on cell proliferation of BCPAP in different concentrations (0 mmol/L, 1 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L) and time course (0 h, 4 h, 8 h, 16 h, 24 h, 48 h). The experiment was divided into four groups: Con, Met, Met+Sal and Met+DM, flow cytometry to detect the rate of apoptosis of BCPAP. Then detect the protein expressions of CHOP, GRP78 and Caspase-12 of 4 groups by Western blot. Result:Compared with the experimental control group, the percentage of cell proliferation index significantly decreased in metformin (0-20 mmol/L and 0-48 h) treatment group. Compared with the experimental control group, the percentage of apoptosis cells significantly increased in metformin treatment group. Compared with the control group, the protein expressions of GRP78, CHOP and Caspase-12 were significantly increased in Met group; While compared with the Met group, the protein expressions of GRP78, CHOP and Caspase-12 were significantly inhibited in the Met+Sal group. Conclusion:Metformin can induced availably BCPAP cell apoptosis by activating endoplasmic reticulum stress mechanism. PMID- 29798417 TI - [Expression and clinical significance of Nrf2 and ERK pathway in papillary thyroid carcinoma]. AB - Objective:To explore the expression and clinical significance of nuclear factor erythroid-2 related factor 2 (Nrf2) and ERK sinal in papillary thyroid carcinoma (PTC). Method:PTC microassy were detected by immunohistochemical method (IHC). The expression of Nrf2, ERK2 and p-ERK1/2 in PTC, para-carcimoma and normal thyroid tissue were detected by Western blot. The transcriptional level of Nrf2 mRNA in PTC, para-carcimoma and normal thyroid tissue were detected by real-time quantitative PCR (qPCR) method. Result:Nrf2, ERK2, p-ERK1/2 protein were high expression in group of lymph node metastasis PTC and negative or weak positive expression in para-carcinoma tissue (P<0.01). And the proteins of clinical stage III-IV of PTC groups express higher than without lymph node metastasis group and clinical stage I-II of PTC group (P<0.05). The expression of Nrf2 protein was positively correlated with ERK2 and p-ERK1/2 protein in PTC (r=0.723 2,r=0.668 6,P<0.05). The Western blot results of Nrf2, ERK2, p-ERK1/2 had a higher level in PTC than those of paracarcinoma and normal thyroid tissue (P<0.01). The level of Nrf2 mRNA were higher than those of paracarcinoma and normal thyroid tissue (P<0.01). Conclusion:High expresion of Nrf2 may be associated with the progression of papillary thyroid carcinoma, and may relate to the high expression and activity of ERK pathway. PMID- 29798418 TI - [Effect of recombinant human interleukin-11 treatment on prognosis of patients with radiochemoradiotherapy in the treatment of nasopharyngeal carcinoma]. AB - Objective:To investigate the effects of recombinant human IL-11 treatment on prognosis of patients with radiochemoradiotherapy in the treatment of nasopharyngeal carcinoma. Method:Seventy-eight cases of nasopharyngeal carcinoma patients were selected as the research object, all the patients were equally divided into observation group and control group with 39 cases in each group accorded to the random draw envelope principle. The control group received conventional chemoradiotherapy treatment, the observation group received the IL 11 treatment based on the treatment in control group, the treatment cycles in the two groups were 2 cycles. Result:After treatment, the total effective rates of the observation group and the control group were 87.2% and 59.0%, respectively, the total effective rate of the observation group was significantly higher than that of the control group (P<0.05). There were 14 cases of grade 0 radiation induced oral mucositis, 6 cases of grade I, 14 cases of grade II, 5 cases of grade III in the observation group during the treatment; There were 28 cases of grade 0 radiation-induced oral mucositis, 5 cases of grade I, 4 cases of grade II, 2 cases of grade III in the control group during the treatment there was statistically significant difference between the two groups (P<0.05). After treatment, the serum CRP of observation group and control group were (5.32+/ 1.92)mg/L and (12.44+/-2.48)mg/L that were significantly lower than before treatment of the (24.59+/-3.14)mg/L and (24.12+/-2.87)mg/L (P<0.05), serum levels of CRP after treatment in the observation group were significantly lower than the control group (P<0.05). After treatment, the pain scores of the observation group and the control group were significantly lower than those before treatment (P<0.05), and the pain scores of the observation group after treatment were significantly lower than the control group (P<0.05). Conclusion:The application of recombinant human IL-11 in the treatment of nasopharyngeal carcinom patients with radiochemoradiotherapy can decrease the expression of CRP, reduce the pain, relieve the oral mucositis and improve the prognosis. PMID- 29798419 TI - [Study on the recent application of ear correction model in children with congenital auricular deformity]. AB - Objective:To study the short-term effect of Earwell ear correction model on congenital auricular deformity in children. Method:Selected 38 children with ear malformation, a total of 42 ears, born at the age of 7 days to 176 days, and the average age was 62.40 days, and all of patients were used the U.S. Earwell correction model for correction. Result:Final auricular morphologic results were classified as excellent (normal shape), good (nearnormal shape), and poor (slight or no improvement). And the patients were divided into group 1 (neonatal period), group 2 (28-90 days) and group 3 (more than 90 days) according to age, after using the Earwell ear correction device, the result which evaluated excellent are 100.00%, 89.47% and 72.73% respectively, and the average correction times are 16.75 days, 26.26 days and 38.91 days respectively, the ratio of complications are 0, 73.68% and 100.00% respectively. Conclusion:The effection of Earwell ear correction model is significant for the correction of children with congenital auricular deformity , the earlier treatment cause the better result, the shorter of the correcting time , and the lower of the complication rate. PMID- 29798420 TI - [The standardization of inflammation detecting methods in upper and lower airways]. AB - Objective:To investigate the standardization of inflammation detecting methods in upper and lower airways. Method:After a five year cooperation with Guangzhou Institute of Respiratory Diseases on inflammatory diseases of airways, we have found a series of evaluation methodology and normative values in upper and lower airways (NO), airway hyper reactivity and cytology (Eos). Result:The normative range of nasal and pulmonary NO is 400-900 ppb and 5-25 ppb respectively. The nasal resistance increased >=100% and FEV1 fell >=20% when compared with their respective baselines both illustrating a positive result. The positive value of nasal and pulmonary Eos are >=2.00/HP and >=2.5% respectively. Conclusion:The standardization of evaluation methods for upper and lower airway inflammation provides the methodology and research basis for follow-up studies of upper and lower airways. PMID- 29798421 TI - [Application of scar skin dilatation in repair of auricular defects after burn]. PMID- 29798422 TI - [Nasal sinus tuberculosis misdiagnosed as chronic nasal sinusitis in 2 cases]. PMID- 29798423 TI - [Synchronous multifocal laryngeal squamous carcinoma a case report]. AB - An aged female complained intermittent hoarse 10 years, without swallowing and breathing difficulties. A month ago, this patient's voice hoarse became worse, she also had sore throat and pharyngeal foreign body sensation at the same time. There are visible lesions on the right side of the vocal cords, anterior commissure and on the left side of the ventricular bands. Laryngeal CT: the right side of the vocal cords has increased thickness, and hyper density with mild enhancement. PMID- 29798424 TI - [Treatment for the external auditory canal lesions in the psoriasis patient: a case report]. AB - A case of a psoriasis patient with the lesions in the left external auditory canal is reported. A 34-year-old male patient has the symptoms of left hearing loss and aural fullness for 8 years. Physical examination: left external auditory canal was full of granulation tissue. Ear HRCT: the left external auditory canal filled with tissue, no damage of the external auditory canal bone. Pure tone audiometry: mild conductive hearing loss in the left ear. Clinical diagnosis: psoriasis lesions in left external auditory canal, psoriasis vulgaris. PMID- 29798425 TI - [Lateral semicircular canal cupulolithiasis in children: a case report]. AB - We report a case of lateral semicircular canal cupulolithiasis in a 12 years old child. He presented to ENT clinic due to vertigo and nausea for 4 hours. Roll test showed strong apogeotropic nystagmus for about 70 seconds when roll to the left recumbent position. The right lateral semicircular canal cupulolithiasis was diagnosed. The child was treated with the Li's quick repositioning maneuver and the vertigo was disappeared. His symptoms did not occurred after 6 months follow up. PMID- 29798426 TI - [Review of 1 000 Hz probe tone tympanogram applying to evaluate middle ear of infants]. AB - 1 000 Hz probe tone acoustic admittance test as a efficient method used to evaluate function of middle ear in infants, has reached consensus from domestic and foreign scholars. But there still exsits controversy on proper use in infants of months old. Here is to make a brief introduction about physiological characteristics of middle ear in infants, 1 000 Hz tympanometry and applicable age range, hoping to providing reference for future research. PMID- 29798427 TI - [Progress in the role of neurotrophin-3 and its receptors in the development of cochlear spiral ganglion in rats]. AB - Neurotrophin-3 (NT-3) attracted increasing attention about NTFs researches in recent years. But the mechanism of promoting the development of neurons and neurite extension is not clear. Recombinant human NT-3 or NT-3 gene is commonly used in the treatment of peripheral and central neurons system damage. When rats are born, the cochlear is not mature yet. It is a suitable experimental animal for studying the morphological and functional development of the peripheral auditory pathway. It was found that NT-3 could promote the survival, growth, division and extension of the cochlear neurons in rats. To make clear the role of NT-3 in the development of spiral ganglion in the rat cochlear will be of significance for the treatment of nervous hearing loss by NT-3 in the future. PMID- 29798428 TI - [Research progress on cochlear implantation in patients with unilateral deafness]. AB - Cochlear implantation (CI) is a relatively new therapeutic method for patients with severe-to-profound unilateral sensorineural hearing loss. Acoustic signal can stimulate the ear directly, thus patients can gain better binaural hearing. This passage has reviewed the recent researches about CI for patients suffered from single side deafness. It can improve the ability of sound localization and speech recognition in noisy environment for patients, in addition, it may relieve tinnitus to some degree. But the long-term effect and indication selection still need further study. PMID- 29798429 TI - [Classification and clinical research progress of sudden deafness]. PMID- 29798430 TI - [Research progress on the etiology of bilateral sudden deafness]. PMID- 29798431 TI - [A clinical analysis for sudden sensorineural hearing loss withcontralateral sensorineural hearing loss]. AB - Objective:To analyze the clinical characteristics and prognosis,and to learn the impact factors of patients with sudden sensorineural hearing loss with contralateral sensorineural hearing loss(SSHLwCSHL).Method:Clinical data of 63 cases of patients with SSHLwCSHL were analyzed systematically,including all the clinical manifestations,audiologic characteristics and the effect assessment,and compared with that of unilateral sudden sensorineural hearing loss(USSHL) and bilateral sudden sensorineural hearing loss(BSSHL).Base on those,we summarized comprehensively the development and prognosis characteristics of the disease.Result:The incidence of SSHLwCSHL was 8.3 percent of overall patients with SSNHL.SSHLwCSHL occurs more commonly in male patients,with more vertigo,diabetes mellitus,and lipid panel abnormalities compared with other groups.Hearing curve and the degree of hearing loss of the prevalence ear of SSHLwCSHL was statistically significant difference with USSHL(P<0.05).Most common reason of the contralateral hearing loss was sudden sensorineural hearing loss(49%),and 59% patients of SSHLwCSHL suffered hearing loss of other ear after 2-10 years after contralateral hearing loss.The total effective rate was 14.3%,1 in 63 patients cured,1 excellence and 6 effective.The total effective rate was 9.5% in patients with severe or profound sensorineural hearing loss in the contralateral ear,which was lower than that of patients with moderate and moderately severe sensorineural hearing loss in the contralateral ear(P=0.021).Conclusion:SSHLwCSHL has complex condition.The prognosis for improvement is poor.Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients. PMID- 29798432 TI - [The role of word recognition score in outcomes assessmentof idiopathic sudden sensorineural hearing loss]. AB - Objective:To investigate the change of word recognition score(WRS) during the treatment of patients with idiopathic sudden sensorineural hearing loss(ISSNHL) and explore the role of WRS in outcomes assessment of ISSNHL.Method:Thirty-seven patients diagnosed with ISSNHL,whose pure-tone average(PTA) has no change but WRS has improved after treatment,were analyzed retrospectively.The WRS and the test intensity for WRS of pre-treatment and those of post-treatment were compared statistically.Result:There is statistical significance between WRS of post treatment and that of pre-treatment(P<0.01).The increase of WRS score is consistent with improvement of symptom in these patients.Conclusion:More attention needs to be paid to WRS during treatment of ISSNHL patients,especially those whose PTA has no improvement but patients feel better about their hearing,and WRS could be an important factor in terms of outcome assessment during treatment of ISSNHL patients for the further treatment. PMID- 29798433 TI - [Analysis of tinnitus with sudden deafness]. AB - Objective:To explore the pathogenesis of tinnitus.Method:Retrospective analysis of 192 patients with sudden deafness was done with the characteristics.Charactier of tinnitus and the factors that may affect tinnitus.Result:The intense of tinnitus is related with sex,chi2=14.704,P<0.01,and with age increased,the difference was more significant.The intense of tinnitus has not significant difference between age group with 45 years old(chi2 =6.515,P>0.05) and the classification of sudden deafness and the degree of hearing loss(chi2=7.783,P>0.05,chi2=17.374,P>0.05).Conclusion:Tinnitus was the protection mechanism of the body,and the intensity was irrelevant to hearing loss.On one hand,there may be different modulate systems between different individual,on the other hand,women over 45 years old were more suffered from the severe tinnitus. PMID- 29798434 TI - [The characteristics of the patients with BPPV accompanied byidiopathic sudden sensorineural hearing loss]. AB - Objective:To investigate the characteristics of the patients with BPPV accompanied by idiopathic sudden sensorineural hearing loss(ISSNHL).Method:Retrospective analysis of 150 cases of patients with ISSNHL.All data of the cases were collected,including history,pure tone audiograms and VNG tests.Result:16.0% of all patients had BPPV accompanied by ISSNHL.77.8% of these patients had an abnormal caloric test result.73.9% of them had a profound hearing loss.The hearing outcome between those with and without BPPV had no significant difference.Conclusion:Patients with BPPV accompanied by ISSNHL seem to have a more severe damage than those without BPPV,while the hearing outcomes seem no significant difference between them. PMID- 29798435 TI - [Clinical characteristics of sudden low-tone hearing loss]. AB - Objective:We aimed to investigate the prognosis and clinical characteristics of patients with acute low-tone sensorineural hearing loss(ALHL) and the patients with sudden low-tone loss who were not classified in the audiometric definition ALHL of(non-ALHL).Method:Two hundred and seven patients diagnosed at the university hospital with idiopathic sudden low-tone loss of sensorineural hearing loss including 48 ALHL and 159 non- ALHL from Jan 2010 to Dec 2015.The patients were followed up in the long term with three months to 5 years.The rates of recurrence and/or progression to Meniere's disease for patients with ALHL were compared with those for non-ALHL patients.Result:The recurrence rate was 26.4% for non-ALHL and 16.7% for ALHL.There was statistically significant difference between the two patient groups.In ALHL patients,8.8% patients progressed to Meniere's disease,1.9% was diagnosised with acoustic neuroma and 5.7% with vestibular migraine.In non-ALHL patients,4.2% patients progressed to Meniere's disease.Conclusion:In clinical practice,sudden low-tone loss other than ALHL shows a potential for recurrence and progressed to Meniere's disease. PMID- 29798436 TI - [Curative effect analysis of different degree of hearing lossin sudden deafness patients]. AB - Objective:Through analysis of the clinical data for different degree of hearing loss in patients with sudden deafness,to learn the relationship between degree of hearing loss and therapeutic effect.Method:By selecting for nearly three years 264 cases of patients with sudden deafness hospitalized in our department,we classified them by the level of hearing loss,to comparatively analyze the therapeutic effect on different degree of hearing loss in patients with sudden deafness.Result:The more severe the degree of low-frequency hearing loss,the worse the therapeutic effect.In all frequency sudden deafness,there were no clinically significant in mild and moderate sudden deafness(P>0.05);The cure rate and effective rate among mild,moderate and total sudden deafness are statistically significant(P<0.05),and between severe and total sudden deafness recovery rate are statistically significant(P<0.05);and mild and severe as so(P<0.05),the rest are no statistical significance(P>0.05).Conclusion:The degree of hearing loss has important influence on the curative effect of sudden deafness. PMID- 29798437 TI - [The reclassification of sudden deafness]. AB - Objective:Reclassified the total deafness and flat type of sudden deafness,identified the relationship between new classification and hearing prognosis.Method:To analyze 192 cases of patients with sudden deafness,especially for 159 cases of flat type and total deafness patients for further curve type classification,classified as rise,decline and consistent,analysis the possible factors with hearing in multiple factors using regression analysis.Result:According to age group of 45 years old,P>0.05,the difference has not statistically significant;Course of the disease according to the 0-7 days and 14 days more,P<0.01,OR=4.291;8-14 days and 14 days,P<0.05,OR=2.983;According to the flat type and total deafness grouping,P<0.05,OR=0.409;According to the curve type of deafness,the difference between rise type and total deafness was significant,P<0.01,OR=9.692;Decline type,consistent type compared to total deafness type,there is no statistically significant difference,P>0.05.Conclusion:According to the pathogenesis of classification,sudden deafness can be divided into rise type,decline type and consistent type.The pathogenesis of rise type may be different degree of hydrops of inner ear.Decline type may be hair cell damage,and consistent type may be related to the damage of vascular stria and potential labyrinthitis,prognosis is poorer. PMID- 29798438 TI - [Characteristics of tinnitus related to idiopathic suddensensorineural hearing loss in 272 patients]. AB - Objective:To investigate the characteristics of sudden sensorineural hearing loss (SSHL) patients with tinnitus.Method:Two-hundred and seventy two SSHL patients with tinnitus underwent evalution through Tinnitus Handicap Inventory(THI) and Tinnitus Questionnaire(TQ).Demographic data and tinnitus characteristics were analyzed.Result:In 272 patients,41.6% of patients suffered from low frequency tinnitus,2.0% with medium frequency tinnitus,56.4% with high frequency tinnitus.There were 79% patients whose tinnitus were continous,while 21% were intermittent;From the view point of daily life compromising,37.4% were minor,44.8% were moderate,17.8% were serious.The most important factors that deteriorate tinnitus were bad sleep,noise,life pressure and tiredness.Conclusion:There were individual differences among patients with sudden deafness and tinnitus.Enough evaluation should be made to decrease the infection of tinnitus. PMID- 29798439 TI - [An analysis of various diseases and hearing screening in NICU infants]. AB - Objective:It is the first time to study the hearing screening results in NICU infants in Heilongjiang province,to analyze the various diseases and hearing loss distribution in NICU infants.Method:Three hundred and thirty four newborns(668 ears) in NICU received hearing screening with TEOAE and AABR test.We compared the results of different risk factors.Result:The failed ratio of different diseases in NICU are as follow: premature infants 61%,hypoxic-ischemic encephalopathy(HIE) 35%,neonatal infectious pneumonia 30%,neonatal sepsis 30%,neonatal aspiration pneumonitis 36%,neonatal jaundice 29%.Conclusion:The positive ratio of preterm infants was 61%,which is higher than the other diseases in NICU infants of Heilongjiang province.Both TEOAE and AABR failure have a high incidence of abnormal hearing status.Neonatal jaundice,neonatal infectious pneumonia and premature infants diseases are the high risk factors of auditory neuropathy spectrum disorder(ANSD) in NICU infants of Heilongjiang. PMID- 29798440 TI - [A hereditary hearing loss case accompanied by unilateral sudden hearingloss:GJB2 235delC homozygotes related late-onsetmoderate hearing impairment]. AB - Summary A sporadic,case suffering from sudden hearing loss of left ear accompanied by tinnitus when he visited our hospital in 2015,whose hearing threshold had a fluctuation in recent two year.Mutation screening of GJB2 gene,was carried out on the case and his parents by polymerase chain reaction amplification and Sanger sequencing.Targeted 307 genes capture and next generation sequencing(NGS) was performed to explore,additional possible genetic codes.GJB2 235delC homozygotes were identified,and NGS showed no other pathogenic,likely pathogenic variations or modifier genes.The overexpression of Connexin30 or the presence of modifier genes may be the possible mechanisms of the late-onset moderate hearing impairment phenotype,and much more cases collection and further in vivo/vitro experiments need to be done to decipher the genetic code. PMID- 29798441 TI - [The application of U-shaped cartilage-perichondrium tympanoplastyfor subtotal tympanic membrane perforation]. AB - Objective:To evaluate the anatomical and functional results of U-shaped cartilage perichondrium tympanoplasty for subtotal tympanic membrance perforation.Method:A retrospective study was carried out 45 patients(45 ears) with chronic otitis media treated with U-shaped cartilage-perichondrium tympanoplasty.Patients were followed up to assess anatomic and functional results and the data was analyzed statistically.Result:Forty-five cases were followed up successfully,all cases had a tympanic membrane with no irregularities(100%),and the average air-bone gaps of pure tone audiometry of 0.25,0.50,1.00,2.00,4.00 kHz were reduced significantly(P<0.05).Conclusion:U-shaped cartilage-perichondrium tympanoplasty for subtotal tympanic membrane perforation is good with high survival rate and better results of hearing. PMID- 29798442 TI - [The value of area curve ratio electrocochleography in diagnosisof Meniere's disease during different periods]. AB - Objective:To evaluate the value of summating potential /action potential (SP/AP) area curve ratio in diagnosis of Meniere s disease(MD) during acute attacks and quiescence phase.Method:The normal control group and the MD group during acute attacks and quiescence phase received electrocochleography(EcochG)examination.The SP/AP amplitude and area curve ratios were measured respectively(to derive the SP/AP amplitude and area curve ratio),with normal SP/AP amplitude and area curve ratios of EcochG were identified,and analysed the results of EcochG in MD acute attacks and MD quiescence phase and the normal control group.Result:The upper limit of normal for SP/AP amplitude and area curve ratio were respectively 0.40 and 1.78.The SP/AP area curve ratio positive rate during acute attacks was 95.56% and SP/AP amplitude ratio was 71.77%.SP/AP area curve ratio positive rate during quiescence phase was 55.56% and amplitude ratio was 33.33%.The results showed that there were significant different between the two markers(P<0.05).The positive rate which during the period of acute attacks was higher than that quiescence phase period,The positive rate of the SP/AP amplitude and area curve ratios between acute attacks and quiescence phase were significant different(P<0.05).By the F rest,the SP/AP area curve ratio parameters in MD acute attacks and MD quiescence phase and the normal control group were compared,and the difference was significant(F=111.10,P<0.05).There were significant different between the two groups among three(P<0.05).The SP/AP area curve ratio parameters among the MD acute attacks and MD quiescence phase and the normal control group were significant different(F=65.68,P<0.05).There were significant different between the two groups among three(P<0.05).Conclusion:It can increase the positive rate when undergo the EcochG examination during acute attacks of Meniere's disease,while the SP/AP area curve measures are more sensitive than SP/AP amplitude ratio in diagnosis of Meniere's disease. PMID- 29798443 TI - [Efficacy of different treatment on residual symptoms aftercanalith repositioning procedure in patients withbenign paroxysmal positional vertigo]. AB - Objective:To assess which methods are effective for residual symptoms after canalith repositioning procedure in patients with benign paroxysmal positional vertigo(BPPV) then guide the clinical treatment.Method:A total of 93 cases who were diagnosed with BPPV,then after the canalith repositioning procedure,which still have residual symptoms were enrolled in our study.They were randomized into three groups,The control group(A),The drug group(Ginkgo Leaves Soft-gel Capsule and Qiangli Dingxuan tablets)(B),The vestibular rehabilitation gymnastics group(C).Then compare the efficacy of different treatment.Result:In the follow-up of 30 days,the number of DHI scores decline of group A is significantly lower than that of group B(P<0.05) and C(P<0.05),making statistical significance.The residual symptom duration of group A is significantly longer than that of group B(P<0.05) and C(P<0.05),making statistical significance.There is no significant statistical difference in comparing the number of DHI scores decline in the follow-up of 30 days,and the residual symptom duration of B and C(P>0.05).Conclusion:The drugs for improve the microcirculation and vestibular rehabilitation gymnastics can reduce the duration of residual symptoms. PMID- 29798444 TI - [The clinical study of the treatment of auricular pseudocyst with Suture following by pressure dressing]. PMID- 29798445 TI - [Clinical application of acellular dermal matrix on repairingexternal auditory canal skin defects]. PMID- 29798446 TI - [Eosinophilic granuloma of the temporal bone: a case report]. AB - One case of Eosinophilic granuloma of the temporal bone was reported which had been misdiagnosed as cholesteatoma.This disease is a rare benign tumour that is lack of specific feature in clinical performances and easy to be misdiagnosed. PMID- 29798447 TI - [Primary ectopic meningioma of the middle ear:a case report]. AB - Extracranial meningioma involving the middleear is extremely uncommon.We report a case of a primary ectopic meningioma of themiddle earand clinically presenting as tinnitus with hearing loss.This case report highlights important considerations and pitfalls in the diagnosisand treatment methods of this tumour. PMID- 29798448 TI - [Challenge in the management of benign paroxysmal positional vertigo]. AB - Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder,which is defined as a disorder of the inner ear characterized by repeated episodes of positional vertigo as changes in head position.The effective positioning maneuvers has made BPPV the most successfully treated type of vertigo.However,some patients experience a serious disturbance with residual vertigo,light cupula and persistent or repeated attacks of BPPV even after several trials of canalith repositioning procedures.In this article,the challenge as light cupula,management of residual vertigo and repeated attacks of BPPV after canalith repositioning procedures were reviewed. PMID- 29798449 TI - [Clinical diagnosis and treatment progress of acute otitis externa]. AB - Acute otitis externa(AOE) is defined as diffuse inflammation of the external ear canal skin or subdermis occurred in 3 weeks,which sometimes may also involve the pinna or tympanic membrane.Clinical manifestations include:otalgia,itching,fullness,sometimes with hearing loss.The hallmark sign of AOE is tenderness with movement of the tragus or pinna AOE Often occurs in adults or children older than age of 2,while little morbidity in children under the age of 2.Lifetime incidence is up to 10% in a persons life.Recently,a lot of different versions of the AOE clinical practice guidelines were published abroad.In this review ,the etiology,diagnose,therapy,prevention,are comprehensive described,which on the basis of evidence-based medicine. PMID- 29798450 TI - [The application of acoustic stapedial reflex in hearing screening of infants]. AB - Nowadays,the newborn hearing screening has carried out in China generally.Acoustic stapedial reflex,which could detect problems in the stapedial reflex pathway,is one of the general screening tools.Because of the immatureness of hearing system and poor cooperation of infants,we should build new standards of infants when testing acoustic stapedial reflex.The paper has summarized the studies about acoustic stapedial reflex on infants,which may guide the clinical work. PMID- 29798451 TI - [Progress in the tests of eustachian tube function]. AB - The eustachian tube is a narrow canal which connects the back of the nose with the middle ear cavity.It is made up of a bony component comprising the lateral one third and a cartilaginous component comprising the medial two thirds.The eustachian tube is responsible for three main physiologic functions:1pressure equilibration,2fluid clearance from the middle ear,3protection of the middle ear from pathogens,which help maintain an air filled and fluid free cavity to allow sound transmission.Eustachian tube dysfunction(ETD) is a common middle ear disease which may manifest tympanic membrane atelectasis,otitis media with effusion and attic retraction pocket.ETD is often linked to the underlying possible cause of many middle ear diseases.The diagnosis of ETD relies on the accurate assessment of the Eustachian tube function and different tests have been developed for this intention during the past few decades.In this review we will discuss the application of these tests of Eustachian tube function. PMID- 29798452 TI - [Management of chronic rhinosinusitis]. AB - Chronic rhinosinusitis(CRS) is a common upper respiratory tract disorder that involves chronic inflammation of the nasal and paranasal sinus mucosa.CRS can be subdivided into two categories: CRS with nasal polyps(CRSwNP) and without nasal polyps(CRSsNP).The management of CRS usually involves medical treatment and surgical treatment.A long-term anti-inflammatory treatment is the key for curing CRS.On the other hand,surgery should be considered when there is persistence the symptomatology despite a maximal medical treatment.For those repeatedly recurrence cases,the surgery usually as an adjunct to the medical treatment.On the basis of distinct phenotypes and endotypes of CRS,the management of CRS is extremely individual and must be discussed case by case in the future. PMID- 29798453 TI - [Clinical analysis of delayed epistaxis after craniofacial trauma in 16 patients]. AB - Objective:To investigate the etiology,clinical presentations,diagnosis and treatment of delayed epistaxis after craniocerebral trauma.Method:A retrospective analysis was made including 16 cases who had the traumatic carotid artery injury with massive delayed epistaxis.All of them were finally diagnosed by digital substraction angiography(DSA).Final clinical outcome,radiographic data and follow up data were analyzed.Result:Two cases of traumatic pesudoaneurysm from internal maxillary artery were embolized with polyvinyl alcohol particles and gelatin sponge.Fourteen cases of traumatic pesudoaneurysm located in ICA cavernous segment was embolized by covered stent.The covered stent placement was successful in all 14 pseudoaneurysms.No procedure-related complications or deaths occurred during follow-up except one of the case with visual field defects and another case with vision loss.Conclusion:Patients with delayed massive epistaxis or recurrent epistaxis after craniofacial trauma which cause pesudoaneurysm should undergo CTA,MRA or DSA examination,and it is would help to get proper diagnosis and treatment as early as possible.No recurrence was found after successful endovascular techniques. PMID- 29798454 TI - [Analysis and evaluation of droplet digital PCR for H.pylori infections in chronic tonsillitis]. AB - Objective:To investigate the measurement effect of droplet digital PCR(dd-PCR) for H.pylori infections in chronic tonsillitis and explore the correlations between H.pylori infections and chronic tonsillitis.Method:The subjects consisted of 48 chronic tonsillitis patients aged between 7 and 52 years scheduled for tonsillectomy.Core biopsy samples from resected tonsillary tissue was tested for H.pylori detection using both RT-PCR and dd-PCR for the CagA and VacA genes.Preoperative patient venous blood samples were also tested for H.pylori antibodies by Enzyme-linked immunosorbent assay(ELISA).ELISA,RT-PCR and dd-PCR were also used to detect expression of CagA and VacA genes in plasma and tissue of 30 cases of obstructive sleep apnea syndrome(OSAHS) and 35 cases of plasma from healthy subjects.Result:The expression of H.pylori antibodies is tested in plasma:48 chronic tonsillitis patients(10.12+/-3.23)ng/ml, OSAS(9.87+/ 2.43)ng/ml, healthy subjects(9.34+/-3.38) ng/ml.There was no significant difference between groups in the plasma.The VacA and CagA gene sequences were detected by RT-PCR:48 chronic tonsillitis patients VacA(27.1%),CagA(16.7%),VacA+CagA(16.7%);30 OSAHS,VacA(23.3%),CagA(20.0%),VacA+CagA(16.7%);all of which were also positive by dd-PCR,thus were considered H.pylori infected.Moreover,The expression of VacA and CagA increased in tissues testing by dd-PCR:48 chronic tonsillitis patients VacA(72.9%),CagA(52.1%),VacA+CagA(39.6%);30 OSAHS,VacA(33.3%),CagA(23.3%),VacA+CagA(16.7%).Conclusion:Our study supports the possible role of H.pylori in chronic tonsillitis.H.pylori maybe one of the risk factors of chronic tonsillitis.dd PCR had bettersensitivity and specificity compare to H.pylori serological and RT PCR.Feasible anti H.pylori treatment maybe used for H.pylori associated chronic tonsillitis. PMID- 29798455 TI - [The analysis of the allergic rhinitis and chronic rhinosinusitis with nasal polyps]. AB - Objective:To study the influence of allergen,sIgE,total IgE in allergic rhinitis and chronic rhniosinusitis with nasal polyps.Method:Fifty patients with allergic rhinitis and fifty patients with both allergic rhinitis and nasal polyp were involved in this study.Average dense of sIgE and total IgE in serum were dectected. Result:The kinds of allergens between the two groups were siginificantly diffierent;there was no siginificantly diffierence on sIgE average dense(P>0.05);total IgE dense was higher in allergic rhinitis and chronic rhniosinusitis with nasal polyps patients(P>0.05).Conclusion:AR with nasal polyps in patients was high proportion of food allergies and allergic reactions strength was high than the AR. PMID- 29798456 TI - [Efficacy of sublingual immunotherapy and subcutaneous immunotherapy in children with allergic rhinitis]. AB - Objective:To evaluate the efficacy and safety of sublingual immunotherapy(SLIT) and subcutaneous immunotherapy(SCIT) in children with pediatric allergic rhinitis.Method:This study retrospectively analyzed the efficacy and safety of SLIT and SCIT in 186 children with allergic rhinitis which induced by house dust mites.Patients were randomly divided into two groups:SLIT group consisted of 104 patients,and SCIT group consisted of 82 patients.These two groups were followed up 2 years and recorded on the following indexs including total rhinitis symptoms score(TRSS),visual analogue scale(VAS),the rhinoconjunctivitis quality of life questionnaire(RQLQ),skin index(SI),serum specific IgE(slgE), eosinophil cationic protein(ECP),peripheral eosinophil(EOS) and adverse reactions.Result:After 2-year treatment,both SLIT and SCIT groups showed significant reduction ins TRSS,VAS,RQLQ,SI and ECP compared with those before treatment (P <0.05),while there were no significant differences in sIgE of two groups compared with those before treatment(P>0.05).Besides,there were no significant differences between the two groups in TRSS,VAS,RQLQ,SI,sIgE,ECP and EOS (P >0.05) before or after treatment.There were 3 patients in SLIT group and 2 patients in SCIT group who showed adverse reactions.For the incidence of adverse reactions,the figures were 3.85% and 2.44%,respectively.No severe systemic side effects were registered in these two groups.Conclusion:Both SLIT and SCIT demonstrated the improvement of symptoms and quality of life in patients with pediatric allergic rhinitis.The therapeutic efficacy is consistent with SLIT and SCIT.Both SLIT and SCIT groups indicated significantly decrease in SI and ECP,which suggest that SI and ECP may be the potential indicators in efficacy evaluation. PMID- 29798457 TI - [Manifestation of first branchial anomaly:56 cases reportrhinitis]. AB - Objective:To sum up and conclude manifestation of congenital first branchial anomaly(CFBCA).Method:The clinical data of 56 patients from 2005 to 2015 in our hospital were retrospective reviewed.Result:Manifestation:mass without pain(26.8%),repeated sore and discharge(71.4%),otological symptom(external auditory discharge,hearing loss,28.6%).Eleven cases bacterial sample showed positive result,and most of them show pseudomonas aeruginosa and staphylococcus aureus.Auricular endoscopy typically performed stricture of external auditory canal,cholesteatoma samples accumulated in ear canal,fistula at the conjunction of the bone and cartilage and tympanic membranous attachment.Typical performance of CT(MRI)was that there were cystic,lobulated or tubular abnormal shadow related with ear canal in Pochet's triangle area whose cyst wall or pipe wall could been enhanced in enhanced CT(MRI) scans,and part of that could be connected with skin.The statistical difference between type Oslen and Work and clinical characteristics(P<0.01),and the relationship between type Oslen and Work(P<0.01).Most of Work I were cyst type,and these two type often had no infected symptom.Most of them were young patients.Most of Work II were sinus and fistula type ,and these two type often had infected symptom.Most of them were teenagers.Part of patients of type Work II showed tympanic membranous attachment.Conclusion:CFBCA was rare,and it is more common in young patients and often in left part.It always performed as mass without pain,repeated sore and discharge,external auditory discharge.Most of Work I were cyst type,and these two type often had no infected symptom and most of them were young patients .Most of Work II were sinus and fistula type,and these two type often had infected symptom and most of them were teenagers.Auricular endoscopy,CT,MRI could help make diagnose.Doctors clinical need to differentiate it with related diseases according to different manifestations. PMID- 29798458 TI - [Barium sulphate aspiration during upper gastrointestinal examinations: two cases report and review of the literature]. AB - Objective:To investigate the causes of barium aspiration,death rate and the cause of death in the upper gastrointestinal examinations,and to help the doctor selecting a reasonable method in upper gastrointestinal tract examination.Method:Two cases in our hospital was reported,and totally 25 patients in 22 articles were obtained in pubmed or google shchoolar form 1989 to 2014.Purpose of radiologic studies of the upper digestive tract,distribution of the aspirate,clinical presentation and prognosis after aspiration of the sulfate barium in literature were collected.Result:1Aspiration of barium sulfate mainly happened in elderly patients and infant.The age of died group were older than survive group,however,there were no significant difference statistically(F=0.909, P=0.355).2The directly mortality rate associated with barium aspiration was up to 38.1% in adult,and ten patients of them(47.6%) recovered.All the infants were recovered completely form the respiratory distress cause by the aspiration of barium sulfate.3Aspiration may more likelyoccur in certain conditions involving dysphagia and esophageall obstruction by tumor or foreign body.Further,the gastro esophageal reflux,recent esophageal surgery,eructation and vomiting may also increase the risk of aspiration of the aspiration of barium sulfate.4About 84.0% patients were with initial dyspnea,hypotension,respiratory distress or respiratory failure.A minority of patients without significant reactions,only suffered fever and cough(16.0%).5The deposition of barium sulphate were commonly affected both lungs(80.0%).Barium sulfates distributed in unilateral lung only were found in five patients 20.0%.Conclusion:Aspiration may easier occur in certain conditions involving dysphagia and esophageall obstruction by tumor or foreign body.Further,the gastro-esophageal reflux,recent esophageal surgery,eructation and vomiting may also increase the risk of aspiration of the aspiration of barium sulfate.Most of the patients after aspiration of barium were presented with initial dyspnea,hypotension,respiratory distress or respiratory failure.When considerable amounts of barium sulfate are aspirated into the lung leading to arterial hypoxemia and dyspnea,it is mandatory that aggressive treatment with steroids,antibiotics,respiratory physiotherapy,oxygen,and bronchoalveolar lavage is initiated without delay. PMID- 29798459 TI - [microRNA-98 and microRNA-143 in nasal and paranasal sinus carcinomas and its clinical significance]. AB - Objective:To investigate the role and clinical significance of the expression of microRNA-98(miRNA-98)and microRNA-143(miRNA-143)in development and progression of nasal and paranasal sinus carcinomas.Method:The expression miRNA-98 and miRNA-143 was detected by Real time PCR metheod in the 53 nasal and paranasal sinus carcinomas and 50 nasal polyp tissues and 20 cases of normal muscosa.The expression of miRNA-98 was analyzed in nasal and paranasal sinus carcinomas with different clinicopathogical parameters.Result:The expression of miRNA-98 in nasal and paranasal sinus carcinomas was obvious higher than that in inflammation of the nasal polyp tissues and normal muscosa,which had statistical significant difference(P<0.05).There was a positive correlation between miRNA-98 expression and TNM staging ,lymph node metastasis;but not pathological grade.The expression of miRNA-143 in nasal and paranasal sinus carcinomas was obvious lower than that in nasal polyp tissues and normal muscosa,which had statistical significant difference(P<0.05).Conculusion:miRNA-98 highly expressed in nasal and paranasal sinus carcinomas,miRNA-143 lowly expressed in nasal and paranasal sinus carcinomas. PMID- 29798460 TI - [Effects of specific immunotherapy on the expression levels of serum IL-17,IL-35 and Treg/Th17 regulatory T cellsin patients with allergic rhinitis caused by dermatophagoides]. AB - Objective:To explore the regulatory effect of sublingual immunotherapy on the balance of Treg/Th17 cells and the expression of IL-17 and IL-35 in serum of allergic rhinitis(AR) in pre-specific and post-specific immunotherapy.Method:In this study,30 cases were randomly selected from outpatients of otolaryngological department in the second hospital of Hebei Medical university.These were attributed as pretherapy group.After treatment,the same patients were as renamed as the post-therapy group.Another 30 cases were healthy subjects enrolled from physical examination branch of our hospital.We detected the expression level of IL-35 and IL-17 in peripheral blood by using ELISA and defeced CD4+ CD25+ Foxp3+ T cell and CD4+ IL-17+ T cell expression level via flow cytometry.Result:The expression level of IL-17 in pre therapy group was obviously higher than that in control group(P<0.05);The expression level of IL-17 in post therapy group was obviously lower than that in pre-therapy group,The difference was a statistically significance(t=5.030,P<0.05);The expression level of IL-17 in post therapy group was also higher than that in control group(P <0.05 ).The expression level of IL 35 in pre-therapy group was obviously lower than that in control group(P<0.05);The expression level of IL-35 in post therapy was obviously higher than that in pre-therapy group;The difference was a statistically significance (t=-4.083,P<0.05),the expression level of IL-35 in post therapy group was also lower than that in control group(P<0.05).The percentage of CD4+CD25+Foxp3+ T cell in CD4+ T cell was significant lower in pre therapy group than that in control group (P<0.05);The percentage of CD4+CD25+Foxp3+ T cell in CD4+ T cell in post therapy was obviously higher than that in pre therapy group;The difference was a statistically significance(t=-10.584,P<0.05),The percentage of CD4+CD25+Foxp3+ T cell in CD4+ T cell was also lower in post therapy group than that in control group (P<0.05 ).The percentage of CD4+IL17+ T cell in CD4+ T cell was significant higher in pre therapy group than that in control group (P<0.05);The percentage of CD4+IL-17+ T cell in CD4+ T cell in post therapy group was obviously lower than that in pre therapy group.The difference was a statistically significance (t=6.258,P<0.05).The percentage of CD4+IL-17+ T cell in CD4+ T cell was also higher in post therapy group than that in control group (P<0.05 ).Conclusion:Specific immunotherapy can have an impact on the expression levels of IL-17,IL-35 and also on Treg/Th17 cells balance in peripheral blood for patients with allergic rhinitis. PMID- 29798461 TI - [The characteristics of a mouse model with nasal polyp established by lipopolysaccharide]. AB - Objective:To explore the effect of lipopolysaccharide(LPS) on the formation of nasal polyps in mice and its mechanism.Method:Five or ten MUg of LPS were dropped into the nasal cavities of six to eight-week C57BL/6J mice in order to establish animal models with nasal polyps.Buried food pellets experiment was used to assess olfactory function of mice.Hematoxylin-eosin staining,olfactory marker protein(OMP),and myeloperoxidase(MPO) for neutrophil immunohistochemistry were used to observe histopathological changes in the nasal mucosa.The expression levels of cytokines,such as interferon(IFN)-gamma,tumor necrosis factor(TNF) alpha,IL-6 in the nasal lavage fluid,were detected by ELISA.Result:Compared to the control group,mice in the LPS groups showed significant nasal polyp formation,olfactory dysfunction,more MPO+ cells while less OMP+ cells in the nasal mucosa,as well as increased significantly levels of IFN-gamma,TNF-alpha,and IL-6 in the nasal lavage fluids(all P<0.05).Conclusion:LPS from Gram negative bacteria alone can induce the formation of nasal polyps in mice,characterized by more neutrophils,olfactory dysfunction,and increasing Th1 cytokine.Therefore,this model is commensurate with the characteristics of primary nasal polyps found in China and other major Asian.The current study suggests that LPS may be one of the important pathogenesis of gram negative bacteria in the nasal polyps. PMID- 29798462 TI - [Application of 128 slice spiral CT 3D reconstruction in dorsum narrow osteotomy]. AB - Objective:To explore the value of 128 slice spiral CT 3D reconstruction in dorsum narrow osteotomy.Method:Twenty cases of nasolacrimal duct injury patients were collected from January 2014 to June 2015 as observation group;and other 20 cases healthy adults were for control group.Maximum anteroposterior diameter and left right diameter of lacrimal sac,distance of top and bottom of lacrimal sac,the nasolacrimal duct length,nasolacrimal duct wall thickness,nasofrontal angleand the distance of middle turbinate to the top and bottom of the lacrimal sac were analyzed by 128 slice spiral CT 3D reconstruction.Result:In the observation group,the duct length was(11.58+/-11.58)mm,and nasolacrimal duct wall thickness was(1.25+/-0.36)mm.Maximum anteroposterior diameter of lacrimal sac was(0.89+/ 0.14)cm,and left-right diameter of lacrimal sac was(0.66+/-0.06)cm.The distance of top and bottom of lacrimal sac was(1.85+/-0.04)cm.All the parameters were statistically significant compared with the control group(P<0.05).Conclusion:The application of 128 slice spiral CT 3D reconstruction in dorsum narrow osteotomy of lacrimal duct system,not only could efficiently prevent postoperative lacrimal duct system damage,but also has important reference value in the diagnosis of postoperative lacrimal duct system damage. PMID- 29798463 TI - [Quality of life analysis of teachers in a primary school in Chengdu]. AB - Objective:To investigate the prevalence of voice disorder and quality of life in the primary school teachers in a certain district of Chengduand examine the correlation between two voice-specific questionnaires.Method:Random sampling survey included 389 teachers from a certain district of Chengdu.Twelve item general health questionnaire(GHQ-12),voice handicap index 10(VHI-10) and voice related quality of life (V-RQOL) were investigated and routine examination of throat with electronic fiber laryngoscopy were carried out for teachers.Result:There were 189 teachers who had voice disorders(voice disorders group),and 200 teachers who did not have voice disorders(control group).2The total score's difference of V-RQOL and VHI-10,functional(F) and emotion(E) dimensions in VHI-10 between two groups were statistically significant(P<0.05),however,there were no statistically significant difference of GHQ-12 between two groups. The total score of GHQ-12 was positively correlated with VHI-10(r=0.194,P <0.05),while the total score of V-RQOL was negatively correlated with GHQ-12(r=-0.209,P<0.05) and VHI-10 (r=-0.586, P <0.05).Conclusion:Voice disorders can affect teachers' psychology and voice related quality of life.Although the VHI-10 and V-RQOL had correlation,the correlation is not strong.So it is recommended combine VHI-10 and V-RQOL when the quality of life of voice disorders is evaluated. PMID- 29798464 TI - [The diagnosis and treatment strategy for patients with severemultispace abscesses in neck]. AB - Objective:To analyze the clinical characteristics of patients with severe deep neck abscess,etiology,imaging,appropriate treatment selection in those patients,to improve the judgement and understanding of the disease.Method:Thirty cases of severe deep neck abscess treated from March 2010 to June 2015 were retrospectively reviewed,including the clinical characteristics,diagnosis and treatment strategy.Result:The sore throat,odynophagia,dysphagia,fever and difficulty breathing were the most common symptoms of severe deep neck abscess.The causes of deep neck abscess were tooth diseases(5 cases),foreign bodies in pharynx or esophagus(4 cases),the second branchial crack cyst with multiply abscess,uncertain cause(20 cases).Six of the above cases complicated with mediastinal abscess.Radiologic evaluation was performed on all of the patients to identify the most probable location of the abscess:parapharyngeal space,retropharyngeal space,masticator space,carotid space,etc.Twenty-five cases were treated by drainage via incising lateral neck and 4 patientsreceived abscess puncture aspiration.Life-threatening complications were developed in all cases,29 cases were cured but one case dead.Conclusion:The treatment of severe deep neck multispace abscesses should be mindful.Once deep neck abscesses are diagnosed,we should timely undertake surgical drainage via incising lateral neck.Emergency tracheostomy should be perform in some case like severe dyspnea,airway obstrucion.Antibiotics should be appropriately applied,and basic diseases and complications should be carefully controlled. PMID- 29798465 TI - [Meta-analysis on common causes of paraesthesia pharyngis in China]. AB - Objective:To evaluate the common causes of paraesthesia pharyngis in China.Method:By means of searching CBM,and VIP,CNKI,CSCD,WanFang Database,etiology of paraesthesia pharyngis cross-sectional studies published from January 2005 to December 2015.were chosen and R software was used for meta analysis.Result:Sixteen cross-sectional study were chosen with a total of 6 624 cases.Meta analysis results showed that the etiology ratio of non-organic disease,nose and throat inflammation,digestive system disease,thyroid disease,cervical vertebra disease (95%CI)were 17.07(10.06-27.49),55.37(45.86 64.50),15.36(11.95-19.52),1.38(0.89-2.11),1.40(0.89-2.21) respectively.Conclusion:Inflammation of the nose and throat is the most important cause of paraesthesia pharyngis in China,and non organic diseases,digestive system and thyroid,cervical disease are the common causes of paraesthesia pharyngis. PMID- 29798466 TI - [Refractory allergic rhinitis serum levels of vitamin D and vitamin D calcium chewable therapeutic value]. AB - Objective:To survey clinical efficacy of vitamin D calcium chewable tablets in the treatment of adults with refractory allergic rhinitis and investigate the level of 1,25-dihydroxyvitamin D3 in the patients' serum.Method:Sixty cases who were dignosed with adult refractory moderate to severe allergic in our hospital outpatient were admitted in our study from May 2014 to November 2015.Sixty cases of healthy people in our hospital medical center were selected as the control group,serum 1,25-dihydroxyvitamin D3 were detected in all patients and normal controls before the treatment.The control group were treated using fluticasone propionate nasal spray and left cetirizine while the experimental group were added with vitamin D calcium chewable tablets on the basis of the control group. Before treatment and after 2 or 4 weeks of treatment,a visual analog scale of the overall classification of nasal symptoms were used of and clinical symptoms evaluation.Result:Compared with healthy controls,the incidence of serum 1,25 dihydroxy vitamin D3 content is:(17.46+/-4.94)MUg/L and the difference was statistically significant(P<0.0).The symptom scores of the treatment group and control group were significantly decreased before treatment and the difference had statistical significance(P<0.05).After four weeks of treatment,the experimental group of the symptom scores were lower than that of control group.The differences were statistically significant(P<0.05).Conclusion:Serum 1,25 dihydroxyvitamin D3 deficiency is a widespread phenonmenon in refractory allergic rhinitis.Vitamin D calcium chewable tables adjuvant treatment of allergic rhinitis is one of methods with safe,effective,and simple treatment. PMID- 29798467 TI - [Tryptase and ECP are related to olfactory dysfunction in allergic rhinitis]. AB - Objective:Olfactory dysfunction is one of the common symptoms in patients with allergic rhinitis(AR),but the underlying mechanisms are not yet known.The purpose of this study was to explore the underlying mechanisms which tryptase and eosinophilic cationic protein(ECP) lead to olfactory dysfunction in patients with AR.Method:We have compared the results between tryptase,ECP,nasal airway resistance and olfactory function of the patients with AR and analyzed the correlations between them.Result:Patients with AR showed impaired olfactory functions compaired to the control group,but there was no differences in the nasal airway resistance between the two groups.Nasal secretion analysis in the patients with AR showed that the level of tryptase and ECP was increased in comparison with the controls.Conclusion:The increase of tryptase and ECP in the olfactory cleft can lead to olfactory dysfunction in patients with AR. PMID- 29798468 TI - [Establish of standard system in otorhinolaryngology experimental teaching]. PMID- 29798469 TI - [Papillary thyroid microcarcinoma with huge lymph node metastasis and squamous cell cancerization:a case report]. AB - We report a 75 years old woman with papillary thyroid microcarcinoma,and squamous cell cancer was found in her lymph node metastases.The patient was characterized by a cervical mass,which was diagnosed as papillary thyroid microcarcinoma by fine needle aspiration.Total thyroidectomy+right radical neck dissection+VI bilateral neck lymph node dissection were performed for the patient. PMID- 29798470 TI - [Typical carcinoid tumor in sphenoid sinus:a case report]. AB - We report a case of typical carcinoid tumor in sphenoid sinus.A 52-year-old woman presented with a history of nasal obstruction,nasal purulent discharge and occasionally accompanied with blood streaks and hyposmia.All laboratory examinations were normal.Sinus computed tomography showed soft tissue mass in the right nasal cavity,nasopharynx and sphenoid sinus,with thickened locoregional mucosa.No sign of bone erosion was observed.In conclusion the case was diagnosed as typical carcinoid tumor. PMID- 29798471 TI - [Historical evolution and frontier of endolymphatic sac surgery for treatment of Meniere's disease]. AB - Surgical treatment could be necessary for patients with intractable Meniere's disease.Endolymphatic sac surgery is a favorable option as it could preserve patient's hearing and vestibular function.The overall vertigo control rate after the surgery was about 80%.Endolymphatic sac surgery includes several variations,namely sac shunting,sac drainage,and sac decompression.Although their establishment and development have experienced a long tortuous process,the theoretical basis and clinical efficacy of the surgery remain controversial.Meanwhile,new findings and surgical innovation keep emerging.This article introduces the historical evolution and reviews the frontier of endolymphatic sac surgery for treatment of Meniere's disease. PMID- 29798472 TI - [Effects of staphylococcus aureus hemolysin on nasal mucociliary clearance system]. AB - The nasal mucosa directly connected with the outside world,and it is vulnerable to various inhaled harmful factors.Nasal mucosal surface covered with mucus cilia blanket.The cilia have the ability to eradicate alien.So the mucociliary clear(MCC) is called first line of defence.In addition to congenital factors of primary ciliary dyskinesia,a variety of acquired factors such as heat,cold,smoking,bacterial infection can damage the function of MCC,leading to various diseases,especially the occurrence of infectious diseases. PMID- 29798473 TI - [Study on development of rehabilitation therapy for voice problems of hearing impaired children]. AB - The production of voice is related to the coordinated operation of respiratory system,phonation system and resonance system.Sonic wave which is produced by the vibration of vocal fold goes through the resonating cavities to bring the voice out.Hearing and voice are two kinds of functions which are very related.Hearing impaired children have a very strong tendency to be in communication with people by improving the volume of their voice(Lombard's effect).To summarize the reasons,the methods of assessment and therapy of voice problems of hearing impaired children.Review 32 literature related to voice problems of hearing impaired children in the near past 12 years.Hearing intervention and improper way of phonation have great effect on the voice health of hearing impaired children.There are few studies on the therapy efficiency and auditory feedback training of voice problems of hearing impaired children,which are expecting our further study. PMID- 29798474 TI - [Difficult-to-treat chronic rhinosinusitis:current status and perspectives]. PMID- 29798475 TI - [Clinical significance of serum allergen sIgE and peripheral blood EOS in patients with chronic sinusitis with nasal polyps]. AB - Objective:To explore the influnces of allergen sIgE and peripheral blood eosinophilic(EOS) on the severity and surgical outcomes in patients with chronic rhinosinusitis with nasal polyps(CRSwNP). Method:Eighty-nine patients with CRSwNP were enrolled. Before operation, allergen sIgE levels and peripheral blood EOS were detected.All patients were examined paranasal computed tomography(CT). After 3 and 6 months of operation, all patients were examined by nasal endoscopy,Allergen sIgE, peripheral blood EOS, nasal endoscopy score, and CT score were retrospective analyzed. According to the results of allergen sIgE the subjects were divided into two groups: the positive allergens group and negative allergens group. Result:Allergen sIgE were positive in 49 patients(the positive allergens group) and negative in 40 patients(the negative allergens group). The major allergens were Dermatophagoides pteronyssinus(39 patients) and cockroach(16 patients). Between the positive allergens group and the allergens negative group, there were no statistically significant differences in peripheral blood EOS count and EOS percentage and CT scores and nasal endoscopy scores of 3-month postsurgery(P>0.05). There was signifigant diference in the nasal endoscopy scores of 6- month postsurgery between the two groups(P<0.05). In the 89 patients with CRSwNP, peripheral eosinophil count showed no significant correlation with CT image scores and 3-month postsurgery nasal endoscopy scores and 6-month postsurgery nasal endoscopy scores(r=0.119,0.180,0.126,P>0.05). Blood eosinophil percentage was not significantly correlated to CT image scores and 3-month postsurgery nasal endoscopy scores and 6-month postsurgery nasal endoscopy scores(r=0.167,0.263,0.140,P>0.05). Conclusion:Allergen sIgE has some impacts on postoperative outcomes but has no impact on the severity of CRSwNP. Peripheral eosinophil may not affect the severity and surgical outcomes of CRSwNP. PMID- 29798476 TI - [Clinic characters analysis of 52 cases with sinus fungus ball disease]. AB - Objective:To explore the clinic characters and the associated factors for the onset of the sinus fungus ball disease. Method:Analyze 52 cases who have received surgery with sinus fungus ball disease retrospectively. The effect factors of age, sex, occupation, the side of the lesion, involving sinus group number, accompany with merger polyps or not, presence of nasal septum deviation, vesicular middle turbinate, paradoxical middle turbinate, infraorbital cells,routine blood leukocyte classification, serum specific IgE, pathogenic fungi species have all been taken into consideration for statistical analysis. Result:In 52 cases of sinus fungus ball disease, 36 cases only suffered in maxillary sinus, 1 case only suffered in ethmoid sinus, 4 cases only suffered in sphenoid sinus, 7 cases suffered from two sinus lesions with the combination of maxillary sinus and ethmoid sinus in all, 4 cases fuffered from three sinus lesions with the combination of maxillary sinus, ethmoid sinus and sphenoid sinus in 2 cases, maxillary sinus, ethmoid sinus and frontal sinus in 2 cases. 26 cases have the lesion on left side,17 cases on the right side, 8 cases on both sides. Aspergillus is the main pathogenic fungus for sinus fungus ball. Maxillary sinus is the most susceptible single sinus for sinus fungus ball. Nasal polyps is commonly seen in multiple sinuses fungus ball(P<0.01). Single sphenoid sinus fungus ball is more commonly seen in the patients with diabetes mellitus(P<0.01). Lesion side of sinus fungus ball has nothing to do with the nasal anatomy abnormalities of nasal septum deviation, vesicular middle turbinate, paradoxical middle turbinate, infraorbital cells. Conclusion:The present study indicates that maxillary sinus fungus ball is the most common type for sinus fungus ball. Aspergillus is the main pathogenic fungus for sinus fungus ball. Nasal polyps is more involved in multiple sinuses fungus ball,Single sphenoid sinus fungus ball is more commonly seen in the patients with diabetes mellitus. Lesion side of sinus fungus ball has none relationship with common nasal anatomy abnormalities. PMID- 29798477 TI - [Microenvironment of middle meatus involved in pathogenesis of nasal polyps-the possibility and research progress]. AB - Chronic rhinosinusitis with nasal polyps(CRSwNP) is a complicated inflammatory disease, with increasing incidence and high recurrence rate,which the pathogenesis remains unclear. This article reviewed research progress about the relationships between middle meatus microenvironments and pathologic process of CRSwNP: including hypoxia ,microbiome imbalance, innate function of the airway epithelial barrier dysfunction. Pointing out a new direction to figure out pathogenesis of CRSwNP. PMID- 29798478 TI - [Chronic fungal rhinosinusitis:clinical and pathologic characteristics of 40 case]. AB - Objective:To further improve diagnosis and treatment for chronic fungal rhinosinusitis(CFRS). Method:Forty patients with CFRS were treated with nasal endoscopic surgrey(ESS). The key-points of surgery were as follows: 1for single fungal sphenoid sinusitis, fracturing middle turbinate ourward or resecting one third of posterior middle turbinate, enlarging the osseous ostium of sinus, removing sinus fungal ball and polypoid nucosa, and flipping mucosa of ostium inside sphenoid sinus to avoid narrow of ostium;2for fungal maxillary sinusitis, retaining uncinate process or resecting tail of uncinate process, enlarging ostium of maxillary sinus according to surgical field, and resecting lesion tissue;3for frontal-ethmoidal sinus lesion, routine treatment was performed; 4iodoform gauze packing the surgical cavity after soaking it with diluted iodine solution(1?1) for 5 min. Result:Pathological examination indicated that 39 cases were infected with fungus(38 cases with aspergillus and 1 case with mucor, respectively), including 4 cases in which lesion mucosa was invaded by fungus. Of these 39 cases,34 cured after receiving one operation, 4 cases relapsed and finally cured after receiving re-operation or outpatient treatment, 1 case had concomitant sphenoid sinus fibroblastoma with skull base invaded and was remitted after radiation therapy. In addition,1 case was diagnosed clinically as allergic fungal sinusitis although no fungus was found by culture and pathological examination, and the disease was not still controlled completely after several times of recurrence. No complication was observed for all of the cases. Conclusion:ESS is an effective treatment for CFRS, and intraoperative multi-point biopsy may be ignored easily.Confirming whether mucosa of sinus is invaded by fungus as well as pathogenic fungi types will have an important value for postoperative further treatment and reduction of recurrence. Concomitant disease should be considered for the cases with poor curative effect. PMID- 29798479 TI - [Investigate the expression of miRNA-203 in papillary thyroid carcinomaand its effect on cell proliferation]. AB - Objective:To investigate the expression of miRNA-203 in papillary thyroid carcinoma(PTC)tissues and its correlation with clinical pathological parameters,explore its effect on cell proliferation of WRO cell. Method:Thirty cases of PTC tissues, paired normal tissues were collected in our hospital during 2013-2016. The expression of miRNA-203 was determined by qRT-PCR,then the relationship of miRNA-203 expression, clinical pathological parameters were analyzed.WRO cells were transfected with miRNA-203 mimics, then cell proliferation, cell cycle and concerned cyclin protein(CyD1,CyB1) were tested by MTT, flow cytometry and western blot. Result:Compared to the paired normal tissues,tumor tissues showed sifnificantly lower expression of miRNA-203. Upregulaion of miRNA-203 in WRO cells effectively reduced cell growth, G2/M arrest. Mechanistically,in the miRNA-203-mimics-treated groups,cell-cycle-related proteins cyclin B1 was up-regulated, while cyclin D1 was down-regulated. Conclusion:miRNA-203 may play an anticarcinogenic effect in PTC. Upregulation of miRNA-203 is highly correlated with cell prolliferation, and maybe miRNA-203 is a potential targert for the treatment of thyroid carcinoma. PMID- 29798480 TI - [Study on bimodal stimulation for aural rehabilitationdevelopmentin infants with a unilateral cochlear implant]. AB - Objective:To evaluated the aural rehabilitation development of the bimodal stimulation in deaf infants with a unilateral cochlear implant. Method:The 36 infants, suffering from severe-to-profound bilateral sensorineural hearing loss with residual hearing on at least one side, assigned into two groups randomly:18 wore only the cochlear implant(unilateral A group),while the other 18 used the CI and a contralateral hearing aid at the same time(bimodal group).The aural rehabilitation development was evaluated by sound field test and speech rehabilitation tests(including vowels, consonants, tones, monosyllables, disyllables, tri-syllables and selected hearing) after rehabilitation lasting 3 month(T1),6 month(T2)and 12 month(T3)respectively. Result:At time T1,free-field hearing threshold of 500 Hz of unilateral A group was statistically higher than bimodal group. Free-field hearing thresholds of 500 Hz and 1 000 Hz of unilateral A group were statistically higher than bimodal group attime T2(P<0.05).At time T1, vowels, consonants, tones ,monosyllables, and disyllables rehabilitation scores of unilateral A group were statistically higher than bimodal group(P<0.05).At time T2,there were no statistically significant differences between two groups(P>0.05).However,consonants, tones,disyllables, tri-syllables and selected hearing rehabilitation scores of bimodal group were statistically higher than unilateral group(P<0.05). Conclusion:The cochlear implant infants with bimodal stimulation have better aural rehabilitation development with the process of aural rehabilitation gradually.Therefore, it is essential to make full use of the advantages of binaural hearing and to choose the appropriate aural rehabilitation mode for every deaf infant. PMID- 29798481 TI - [Experimental study of autologous fibroblast cell transplantation in the treatment of vocal fold scar]. AB - Objective:To study the change characteristics of vocal cords scar after the implantation of autologous fibroblast cells into the vocal cords. Method:Forty New Zealand rabbits were used for the production of vocal fold scar model by creating a unilateral vocal fold wounds, we take the skin tissues of each rabbits and cultured them via enzyme digestion method to obtain autologous fibroblast cells. The models were separated into the experimental group and the control group, the third generation fibroblast cells with CM DIL labeled were then injected into the surrounding area of the vocal fold scar in the experimental group, the survival situation of the injected cells were observed by fluorescence microscopy after 1 week, histological examination was performed after 1 months to observe the morphological changes of vocal fold scar tissues, RT-PCR method was used to measure the expression variation of typeIcollagen and type III collagen in the vocal cords and the normal vocal cords, respectively. Result:After 1 week of autologous fibroblast transplantation into the vocal folds, the fluorescence labeled cells were observed.1 month after transplantation, the collagen protein in the vocal fold scar tissues was similar to that in the normal vocal folds,the expression of typeIcollagen and type III collagen in vocal fold scars is similar to those in the normal vocal folds. Conclusion:Autologous fibroblast migration into the vocal cords can survive well inside the vocal cords, and the vocal scar can be recovered to normal vocal cord structure after transplantation of autologous fibroblast cells. PMID- 29798482 TI - [Repairmen of the rabbit's oral mucosa by tissue engineering technology]. AB - Objective:This experiment proposed to complicate BMMSCs and PLLA/SF scaffolds, to study its repairing ability for rabbit oral mucosa wound, and try to evaluate the most potential mixed proportion of PLLA and SF for tissue engineering. Method:Separating,cultivating and identifying BMMSCs. Observing cell phenotype of BMMSCs after cultivating BMMSCs in P70S30 PLLA/SF scaffold for one week.Observing the structure change of BMMSCs and P70S30PLLA/SF scaffold complexes after oral mucosa transplantation experiment for a week;Comparing the wound healing rate of composite of BMMSCs and PLLA/SF scafold,PLLA/SF scaffold and nature repair. Result:1There wasn't a significant effect of PLLA/SF scaffold on cell phenotype of BMMSCs.2The wounds fused well with the oral mucosa transplanted composite of BMMSCs and P70S30 PLLA/SF scaffold after a week.3The healing rate of composite of BMMSCs and P70S30 scaffold was the highest.The average healing rate of composite of BMMSCs and P70S30 scaffold was 94.8%,whose difference was statistically significant compared with natural healing and pure scaffold(P<0.01). Conclusion:1The complex composed of BMMSCs and PLLA/SF scaffolds has the potential as an ideal scaffold for tissue engineering oral mucosa.2The complex composed of BMMSCs and P70S30 PLLA/SF scaffolds is the most beneficial to wound healing of oral mucosa,and has the greatest potential for constructing tissue engineering oral mucosa. PMID- 29798483 TI - [The diversity analysis of spontaneous cerebrospinal fluid otorrhea between young children and adults]. AB - Objective:To assess the diversity of spontaneous cerebrospinal fluid(CSF)otorrhear in clinical manifestation,CT,leakage sites and surgical operation between young children and adults.Method:We conducted a retrospective study of 6 consecutive patients who were all underwent the surgery through the transmastoid approach,including 4 adults patients and 2 children.In the 4 adults patients,two patients' bony defects lay on the tegmen mastoideum,one lay on the tegmen tympani,and another one lay on the sinus meningioma angle.None of the 4 adults patients had abnormal inner ear structures.Materials used in repair included free muscle graft,temporalis fascia,and fibrin glue of the 4 adults patients.The 2 children patients were diagnosed with congenital abnormalities of the lateral inner ear,who had bony defects of the foot plate or fenestra vestibule.Materials used in repair included free muscle graft,temporalis fascia,and musclein sequence. Result:No CSF leaks recurred after the operation except one adults patient,who's left ear recurred two times and experienced three operations. Conclusion:The clinical manifestations of spontaneous CSF otorrhea between young children and adults are different,the HRCT scan on temporal bone before the operation is very important.Especially foradults patients,making sure of theleakagesites and numbers isvaluable and significance for thesurgical procedure selection.. PMID- 29798484 TI - [Classification and its application of spontaneous epistaxis under nasal endoscopy]. AB - Objective:Classify spontaneous epistaxis according to bleeding morhology and characteristic saw under nasal endoscopy,in order to investigate the clinical application of this classification. Method:Retrospectively analyze 125 cases with spontaneous epistaxis treated by electric coagulation hemostasis in our hospital from February 2015 to June 2016.According to performances of different sites under endoscopy,93 cases of spontaneous epistaxis are like aneurysm,31 patients with submucosal hemorrhage, and 1 case is not clear. Take endoscopic hemostatic according to the characteristics of the different types of spontaneous epistaxis,then collect and keep endoscopic images, and have conducted analysis. Result:One hundred and twenty-four cases of patients were cured with endoscopic hemostasis, 1 case of endoscopic hemostatic found no obvious bleeder, and he was cured with iodoform gauze tamponaded in his nose after 1 week. Conclusion:For spontaneous epistaxis, this classification and the corresponding hemostatic measures can effectively improve the success rate of hemostasis, and reduce the likelihood of bleeding complications. PMID- 29798485 TI - [The radiologic evaluation of bony density change in chronic rhinosinusitis]. AB - Objective:To correlate abnormal bone density of sinus wall with impaired drainage of sinus cavity. Method:A retrospective radiological study was conducted:pre operative CT scans of 210 patients with chronic rhinosinusitis(CRS) and CT scans of 40 age-and gender-matched individuals(normal group) without sinonasal disease were reviewed. Opacification of the paranasal sinuses and the radiological density of sinus wall were evaluated and analyzed using PHILIPS MxLite View software. Result:The Hounsfield Units obtained from the lamina papyracea in opaque anterior ethmoid sinus and posterior ethomid sinus were statistically significantly higher than that of the no opacification population in AES and PES and that of the normal group. Secondly, the Hounsfield Units of posterior wall in the opaque frontal sinus in patients with CRS were statistically significantly higher than that of the no opacification CRS patient group and the normal group. Conclusion:Inflammatory bone density changes in CRS patients were observed in the opaque sinuses, and few were found in the sinuses that were not opaque sinuses, suggesting that osteitis mainly occurs in sinuses with drainage disorder or mucosa disease. These change implied that HU change might be a mark of intractable disease and surgery. PMID- 29798486 TI - [The relationship between high jugular bulb and tinnitus and hearing disorder]. AB - Objective:To investigate the relationship between high jugular bulb and tinnitus and hearing disorder. Method:Forty-nine inpatient patients with hearing disorder were selected as the case group,and 50 cases as the control group,two groups of patients conducted temporal CT, audiogram to find out the patients who had hearing disorder,and then acoustic immittance, DPOAE, ABR,genetic screening for deafness and tinnitus questionnaire were conducted to the patients with hearing disorder. Result:Sixteen cases of these 99 patients had high jugular bulb,the total incidence was 16.16%, 14 cases in the case group had high jugular bulb, the incidence was 28.57%,only 2 cases in the control group, the incidence was 4.00%, there was significant difference(chi2=11.027,P<0.01)between two groups.For the cases group, 8 cases(57.14%) had hearing loss in the high frequencies, 4 cases(28.57%) in the low frequencies,2 cases(14.29%) in all frequencies;all of these 14 cases with high jugular bulb also had different degrees of tinnitus,12 of which had pulsatile tinnitus(85.71%), vascular pulsatile tinnitus was most common type,2 of which had non pulsatile tinnitus(14.29%).Four common deafness genes GJB2, SLC26A4, mtDNA12srRNA and GJB3 9 mutation screening tests showed no positive mutation in both groups. Conclusion:High jugular bulb has higher incidence in patients with hearing disorder,which may be a risk factor for hearing disorder.Attention should be paid to the influence of high jugular bulb in clinical diagnosis and treatment of hearing disorder. PMID- 29798487 TI - [Voice acoustic study of plasma radiofrequency ablation for the treatment of laryngeal premalignant lesions]. AB - Objective:To study the voice function effect of low temperature plasma radiofrequency ablation in the treatment of patients with laryngeal premalignant lesions. Method:Fifty cases of laryngeal premalignant lesions were treated with low temperature plasma radiofrequency ablation. All of the patients were examined by electronic laryngoscopy and acoustic analysis(F0,Jitter,Shimmer,NNE,HNR) in 2 weeks,1 month,3 months after surgery. Voice acoustic results were compared with a control group of 50 normal adults for the further analysis. Result:Fifty patients with laryngeal premalignant lesions were treated by low temperature plasma radiofrequency ablation.The result showed that 47 patients(94%)were successfully decannulated without serious complications, such as dyspnea, aphonia and anterior glottic stenosis. Acoustic analysis showed that F0,Jitter,Shimmer and NNE were significantly different from normal 2 weeks after surgery(P<0.01).Voice function recovered weakly 1 month after operation(P<0.05).There were no significant differences in the vocal parameters between plasma radiofrequency ablation group and control group 3 months after surgery(P>0.05). Conclusion:Radiofrequency coblation was a safe,minimally invasive and effective surgical method and can be widely used to treat laryngeal premalignant lesions.. PMID- 29798488 TI - [Recent and long-term hearing outcomes in the cases after open tympanoplasty using titanium ossicular prosthesis]. AB - Objective:To analyze recent and long-term hearing outcomes of the patients with chronic otitis media after open tympanoplasty using titanium ossicular prosthesis. Method:Retrospectively analyzed total 84 cases after open tympanoplaty with titanium ossicular prosthesis. The hearing outcomes before and after surgery(6 months and 24 months) were compared. Result:The hearing levels in the cases were improved to different degrees after surgery.Significant differences were showed compared the average pure tone threshold/air bone gap before surgery with the average recent/long-term outcomes after surgery(P<0.01),and no significant difference could be found compared the recent and long-term outcomes after surgery. Conclusion:Hearing level could be improved in the patients after open tympanoplasty using titianium ossicular prosthesis,and the long-term outcome could be steady. PMID- 29798489 TI - [Efficacy assessment with allergic rhinitis treated by desloratadine citrate disodium combined with Tongqiao biyan granule]. PMID- 29798490 TI - [Observation on the curative effect of traumatic perforation of the tympanic membrane subsidizing therapy using compressed facial mask]. PMID- 29798491 TI - [One case of laryngotracheal fungal disease]. AB - Clinical manifestations: a female patient's hoarseness for more than 10 days. Video Laryngoscope: White toothpaste-like albuginea is visilable on the bilateral vocal cords and trachea about 2-3 ring. Pathology: Fungal bacterial mass.clinical diagnosis:Laryngeal fungal disease. PMID- 29798493 TI - [Radiofrequency coblation treatment for the supraglottic larynx neuroendocrine carcinoma: a case report]. AB - In this paper, feasibility of coblation treatment for epiglottis neuroendocrine carcinoma is discussed. The eligible case is operated by plasma, and the recurrence of tumor isn't found during the follow-up period. Hence, neuroendocrine carcinoma which is discovered early and localized can be attempted to resect by this method. However, based on cautions consideration, it also needs to further research for the long-term effect of radiofrequency coblation treatment. PMID- 29798492 TI - [Maxillary supernumerary teeth are misdiagnosed as nasal foreign body: one case]. AB - A male patient,13 years old,is hospitalized due to the congestion on the right side on March 11th 2016.(foreign body in nose?)He was taken a X-ray of surface jaw fault inspection,considering the nasal ectopic teeth on the right side,given the operation to remove from the nasal endoscopic surgery.Now he is recovered. PMID- 29798494 TI - [Efficiency of oral administration of glucocorticosteroid for treating nasal inflammation]. AB - The pathological basis of nasal inflammation is still not well defined. Extensive studies showed the immune response mediated by T cells played an important role in the pathogenesis of nasal inflammation. The inflammation in the nasal membrane could be considered as the common routines for the development of chronic sinusitis(CRS), allergic rhinitis and allergic fungal sinusitis.Glucocorticosteroid, a compound with similar structure with the adrenal cortical hormone, has been commonly used for the treatment of nasal inflammation. To date, its efficiency via nasal membrane has been well acknowledged in clinical practice, while the efficiency of oral administration is still not well defined. In this study, we aim to investigate the efficiency of oral administration of glucocorticosteroid for treating nasal inflammation. PMID- 29798495 TI - [New advancement in diagnosis and treatment of head and neck lymphoma]. AB - Malignant lymphomas are common malignant neoplastic of lymphatic hematopoietic system, and there are different clinic manifestation in different sites. Malignant lymphomas in the head and neck have characteristics in clinic features,pathologic types and the most common locations. This review is about the role of different clinic manifestation, pathologic types and the International Prognostic Idex(IPI)in the evaluation of prognosis in the head and neck lymphoma. PMID- 29798496 TI - [Salvage surgical treatment for local recurrent nasopharyngeal cancer]. AB - The salvage radiation or surgery is the main choice for recurrent nasopharyngeal cancer now. However the recurrent tumor becomes radiation insensitive and meanwhile,morbidity and mortality become higher.Recently the endoscopic salvage surgery has been developed;the collective evidence from a number of such studies suggests that endoscopic nasopharyngectomy is a safe and effective procedure for the treatment of rNPC.This article reviewed related researches about the feasibility,methods, and current situation of endoscopic salvage surgery. PMID- 29798497 TI - [Clinical application of pedicel frontal flap in reconstruction of the nasal defects]. AB - Objective:The aim of this study is to explorethe application of improving the design of the myocutaneous flap and the transfer mode in nasal facial defect. Method:Six cases with nasal defects were treated by using lateral or median vascular frontal flap which is nourished by supratrochlear and supraorbital arteries. Three patients with basal cell carcinoma of external nose and three patients with cranial base tumor were hospitalized and underwent surgeries. Result:There were 6 cases in this cohort, with the largest defect being 6.5 cm*3.0 cm and the smallest one being 3.0 cm*2.5 cm in size. Except one patient was missing, the rest of the patients flaps survived, and wounds were healed by first intention. Among 6 patients, 3 patients were treated with lateral forehead flap, 2 patients were treated with median forehead flap, and 1 patient was treated with oblique forehead flap. The follow-up being conducted for 6 months to 12 months, the flaps were normal color and sensation, satisfactory appearance and functional recovery of forehead region. Conclusion:Forearm myocutaneous vessels running more constant, superficial, rich blood supply, easy to dissect and can provide a larger area flap, suitable for different causes of nasal facial defect repair. Large area of flap can be provided. These may be favorable choice for repair of the nasal defects. The tunnel through which the flap was transferred to the defect should be wide enough to avoid flap necrosis because of pedicel flap constriction. PMID- 29798498 TI - [Study on the characters of wideband tympanometry in newborns with normal hearing]. AB - Objective:The aim of this study is to establish the characteristic of wideband tympanometry (WBT) in neonates with normal hearing. Method:Ninety newborn babies (149 ears) who had received rooming in care and passed hearing screening were randomly selected to test WBT. The screening programme consisted of distortion product otoacoustic emissions (DPOAE) and tympanometry at 1 kHz. The eigenvalue of ear canal volume, middle ear resonance frequency and acoustic absorptivity were obtained initially to explore the influence of gender and mode of delivery on the eigenvalues. Result:1Ear canal volume: The ear canal volume varied within (0.50+/-0.12)ml. The statistically significant correlationwas observed between ear canal volume and gender as well as the way of delivery (P<0.01). 2Resonance frequency: the resonant frequency distributed from 128 Hz to 642 Hz (mean 328.2+/ 125.76 Hz). No statistically significant correlation (P>0.05) was observed between resonance frequency and gender as well as the way of delivery. 3Frequency wideband absorbance function: the shape of the curve showed two peaks and two troughs. The three most values were located in 1 296 Hz, 2 000 Hz and 5 339 Hz. No statistically significant correlation (P>0.05) was observed between acoustic absorptivity and gender as well as way of delivery. Conclusion:Resonance frequency and frequency acoustic absorptivity functions of newborns are different from adults. It is necessary to establish the normal reference value of WBT for newborns in China in order to promote this technique in the clinic. PMID- 29798499 TI - [Analysis of the related factors of attention deficit/hyperactivity disorder and allergic rhinitis in children]. AB - Objective:To investigate the association between symptom of attention deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in children with AR at different sexes and different ages. Method:A total of 439 AR children aged 6 to 12 years were enrolled in this study. Basic information (age, gender, medical history, family history and comorbidities) of children with AR was collected. Results of prick tests on children skin were recorded. (TNSS) and Chinese version of the SNAP-IV scale, children under the guidance of independent completion of children's quality of life of children with nasal conjunctivitis scale (PRQLQ). According to the results of SNAP-IV, children were divided into AR with ADHD group [attention deficit and hyperactivity symptom score (IHS) >1.25] and AR without ADHD group (IHS<=1.25). The differences between the two groups of children were analyzed using group t-test and chi2 test, and the relationship between each parameter and IHS >1.25 was analyzed by binary logistic regression. Result:Using SPSS 22.0 software, among all the included AR children, IHS >1.25 children accounted for 26.4%, IHS >1.25 group AR symptom scores were significantly higher than HIS <=1.25 groups. Univariate analysis showed that children with age, gender, duration of AR symptoms, skin index and PRQLQ subscales had a correlation with IHS >1.25. After controlling for age and gender, duration of AR symptoms and skin index correlated with IHS >1.25 The estimated OR values are 1.807 (95%CI: 1.350-2.419) and 1.912 (95%CI: 1.320-2.772), respectively. The estimated OR values of PRQLQ subscale and IHS >1.25 were 1.657 (nasal symptom score), 1.324 (eye symptom score), 2.48 (non-eye-nasal symptom score), 1.418 (Behavior problem score) and 2.045 (activity and sleep score). The correlation between IHS>1.25 and the skin index and PRQLQ subscales was mainly found in males with stratification of age and gender, and the association between duration of AR symptoms and HIS >1.25 was statistically significant among all groups reflected. Conclusion:The association between attention deficits and hyperactivity symptoms in AR children was correlated with the severity of AR symptoms, duration, and skin index, and this association was more pronounced in males. In children with AR and ADHD, early management of AR symptoms may improve their ADHD symptoms. PMID- 29798500 TI - [Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in children with allergic rhinitis and the change of TGF-beta and IL-13 mRNA level]. AB - Objective:The aim of this study is to evaluate the efficacy of sublingual immunotherapy (SLIT) with standardized dermatophagoides farinae drops and to examine the change of TGF-beta and IL-13 mRNA level after 12 months SLIT in children with allergic rhinitis (AR). Method:Ninety-two children with AR were collected and randomly divided into two groups: SLIT group (n=62) and control group (n=30). Before and after SLIT for 6 months and 12 months, total nasal symptoms score (TNSS) and total medication score (TMS) were evaluated. In addition, the mRNA expression of TGF-beta and IL-13 in peripheral blood mononuclear cells of AR children after immunotherapy were examined by qRT-PCR. Result:There were significant differences (P<0.01) in symptom and medication scores between the two groups after 12 months treatment. The patients in SLIT group had fewer symptoms and lower intake of medication.The rates for well controlled, partly controlled and uncontrolled children were 45.2%, 32.3% and 22.6%, respectively. Five children (5.4%) experienced local adverse events and 1 children (1.1%) experienced mild systemic adverse events. No severe adverse events happened during the treatment. Accordingly, comparing with the baseline value, the mRNA levels of TGF-beta increased significantly, and IL-10 mRNA level decreased significantly in well controlled children after 12 months treatment. Conclusion:SLIT with dermatophagoides farinae drops is efficient and safe treatment for children with HDM induced AR. The change of TGF-beta and IL-13 mRNA level may be considered as an indicator for evaluating the clinical efficacy of SLIT. PMID- 29798501 TI - [Analysis of repositioning nystagmus in patients with posterior canal benign paroxysmal positional vertigo]. AB - Objective:To conclude the four types of nystagmus in the final position during canalith repositioning procedure (CRP) for posterior canal benign paroxysmal positional vertigo (PC-BPPV), and predict the outcome of CRP therapy. Method:Nystagmus were recorded by an infrared charge-coupled devicecamera when underwent CRP therapy, which observed in the final position and concluded into four types. Result:Two hundred and twenty-three patients were included in our research and the results as follow. 1The nystagmus replicates the initial nystagmus during the Hallpike maneuver, which suggests therapeutic outcome,128 cases in total (57.4%). 2The direction of vertical component is composite while the rotary component is the same, also deeming a successful trial, 35 cases (15.7%). 3The direction of both vertical component and rotary component isreverse to the initial, which indicates a poor response, 36 cases (16.1%). 4Twenty-four cases (10.8%) showed no certain nystagmus but exhibit horizontal nystagmus in roll-test, denoting that the otolith moves to the lateral semicircular. At this appointment, the horizontal nystagmus can resolute after several times of barbecue maneuver. There is a significant difference of the one-time success rate (chi2=46.198, P<0.01) and the mean treatment times (t=10.048, P<0.01) between cupulolithiasis and canalolithiasis PC-BPPV. Conclusion:Different nystagmus in the final position of CRP maneuver is important in predicting the repositioning outcome. The one-time success rate of canalolithiasis is better than cupulolithiasis. PMID- 29798502 TI - [Therapeutic effects of psychological intervention combined with manual reduction on benign paroxysmal positional vertigo in the elderly]. AB - Objective:To explore the best treatment for elderly patients with benign paroxysmal positional vertigo (BPPV). Method:Sixty-eight BPPV patients aged 60-85 years were randomly divided into two groups. The control group was treated by simple manipulation. The study group was treated by manual reduction combined with psychological intervention. The curative effect was compared. Result:The cure rates of the control group and the study group were 44.4% and 43.8% respectively, with no significant difference (P>0.05); the effective rates were 52.78% and 87.50% respectively, with significant difference (P<0.05). The recurrence rates of control group and study group were 8.3% and 3.1% after 2 weeks of treatment, respectively, with no significant difference (P>0.05). The recurrence rates at 3 months were 5.6% and 0 respectively, with no significant difference (P>0.05). The difference of SAS and SDS between the two groups after treatment was statistically significant (P<0.05). There was no significant difference in the residual symptoms between the two groups at the first follow-up (P>0.05), and at 1 week and 4 weeks (P<0.05). The residual symptoms of the patients after reoperation were relieved compared with those of the control group. The DHI scores of the study group between 60-70 years old and 71-85 years old group for the first time, after 1 week and 4 weeks were statistically significant (P<0.05), and the residual symptoms in the 60-70 years group were reduced compare to the 71-85-year-old group. Conclusion:Elderly people with BPPV are susceptible to anxiety and depression. Manipulation combined with psychological intervention can promote the curative effect well, but personalized treatment plan should be developed. PMID- 29798503 TI - [The clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China: A Meta analysis]. AB - Objective:To systematically review the clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China. Method:Randomized controlled trials (RCT) of coblation tonsillectomy and conventional tonsillectomy were searched and retrieved through online databases (PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Library, CBM, CNKI, VIP, WanFang, SUMsearch and Google search engine) and related literatures were reviewed up to 30 April, 2017. Two investigators independently screened literatures,extracted data and evaluated the risk of bias assessment tools for RCT using the Version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions. Then, Meta analysis was performed using RevMan 5.3 software provided by the Cochrane Collaboration. Result:A total of 32 RCTs involving 3 197 tonsillectomy patients were included. The results of meta-analysis showed that: the operation time (MD= 17.03, 95%CI -19.78 to -14.28, P<0.00 001), intraoperative blood loss (MD=-27.00, 95%CI -30.44 to -23.56, P<0.00 001), postoperative pain in 24 hours (MD=-2.00, 95%CI -2.65 to -1.35, P<0.00 001), time needed to regain the normal diet (MD= 2.01, 95%CI -2.60 to -1.42, P<0.00001), formation time of white membrane (MD= 2.44, 95%CI -3.96 to -0.93, P=0.002) of patients in the coblation tonsillectomy group were all significantly lower than the conventional tonsillectomy group; while the exfoliation time of white membrane (MD=2.02, 95%CI 0.65 to 3.39, P=0.004) in the coblation tonsillectomy group was significantly longer than the conventional tonsillectomy group. Conclusion:Current evidence shows that, compared with the conventional tonsillectomy group, the coblation tonsillectomy group can significantly shorten the operation time, decrease intraoperative blood loss, alleviate postoperative pain degree during 24 hours, regain the normal diet early and form white membrane early, but delaye the exfoliation time of white membrane. Due to the limited kinds of literature and quality of the included studies, the above conclusions still need to be verified by carrying out more large scale samples and high quality randomized controlled trials (RCTs) studies. PMID- 29798504 TI - [The clinical features and surgical treatment of facial basal cell carcinoma]. AB - Objective:To investigate the clinical features and reasonable surgical treatment of facial basal cell carcinoma (BCC). Method:The clinical features of primary facial BCC from 37 patients were analyzed.All patients were cured by standard surgical excision with intraoperative frozen section examination and ensuring margins negative,the defects were reconstructed by using adaptive flaps after resection. Result:The patients were followed up for 12 to 36 months after operation.Two cases of 37(2/37,5.41%) with unclear margin developed local recurrence during 4-6 months after resection,the cure rate was 94.59% (35/37). Except 4 cases were suffered with distal skin flap necrosis, the others were well developed. Conclusion:The clinical feature of primary facial basal cell carcinoma was various. The complete resection of primary nidus with clear margin is the key to a successful treatment of facial basal cell carcinoma, and satisfactory therapeutic effects can be obtained after repairing defects by using adaptive flaps after resection. PMID- 29798505 TI - [Application of endoscope assisted curved laryngoscope in laryngeal microsurgery of patients with difficulty laryngeal exposure]. AB - Objective:To investigate the feasibility and clinical value of endoscope assisted curved laryngoscopy in laryngeal microsurgery of patients with difficulty laryngeal exposure. Method:The data of 28 patients with difficulty laryngeal exposure underwent microlaryngosurgery with endoscope assisted curved laryngoscopy technique were collected. Result:Surgeries with endoscope assisted curved laryngoscopy technique were completed successfully one-time in all patients. The fully exposure of glottis was 100%. All cases were followed up for 2 to 18 months. No residual disease or recurrence occurred and no obvious complication occurred. Conclusion:Endoscope assisted curved laryngoscopy technique is a useful solution to difficulty laryngeal exposure. It has satisfactory glottis exposure, clear surgical field and fewer complications which is worthy of promotion. PMID- 29798506 TI - [The effect of the indwelling of nasogastric tube on recovery in patients after laryngofission combined with cordectomy and vertical hemilaryngectomy]. AB - Objective:To investigate the effect of the indwelling of nasogastric tube on recovery in patients after laryngofission combined with cordectomy and vertical hemilaryngectomy. Method:A retrospective analysis was performed on 42 patients who underwent laryngofission combined with cordectomy and vertical hemilaryngectomy. According to postoperative indwelling of nasogastric tube or not, patients were divided into two groups of non-indwelling group (Group A, n=20) and indwelling group (Group B, n=22). Furthermore, the incidence of postoperative infection, eating and choking, the time of tracheal tube plugging and postoperative discharge were compared and analyzed between the two groups. Result:The two groups were all returned to normal eating function and successfully removed the endotracheal tube and discharged. There was no significant difference in the incidence of infection, eating and choking between groups (P>0.05); however, the average postoperative plugging time was significantly less in group A than that in group B (P<0.05), and the time of discharge was shorter than that of group B (P<0.01). Conclusion:Postoperative treatment without the indwelling of nasogastric tube after laryngofission combined with cordectomy and vertical hemilaryngectomy can significantly promote the recovery of patients and improve the quality of life of patients. PMID- 29798507 TI - [Association between the expression of MMP1 gene and prognosis in head and neck squamous cell carcinoma]. AB - Objective:The aim of this study is to investigate the expression of MMP1 and prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to identify the potential mechanism of MMP1 in HNSCC. Method:The RNA sequencing data and related clinical data of HNSCC were downloaded from the TCGA public database. The MMP1 gene expression data and corresponding clinical information in the samples were retrospectively analyzed; The data of gene microarray were used to verify the correlation between MMP1 gene and HNSCC. The disease free survival and overall survival of HNSCC were also analyzed; Gene set enrichment analysis was conducted to identify the potential mechanism of MMP1 in HNSCC. Result:Among the 332 HNSCC patients, the expression of MMP1 was significantly associated with lymphatic invasion and tumor grade (P<0.01). The higher the expression level of MMP1 was, the more susceptible the patient was to lymph node metastasis. The data confirmed that the expression of MMP1 in HNSCC was significantly higher than that in normal mucosa (P<0.05); HNSCC of patient in MMP1 high expression group proved to have worse disease free survival and overall survival than in MMP1 low expression group (P<0.05); Gene enrichment analysis indicates that the high expression of MMP1 gene might influence the biological process of tumor though epithelial mesenchymal transition, TGF-beta signaling pathway, hypoxia, angiogenesis, Noth signaling pathway, and up-regulation of KRAS gene signaling pathway. Conclusion:The high expression of MMP1 was related with occurrence and development of HNSCC, which can be used as an independent risk factor and has a great clinical significance. PMID- 29798508 TI - [The diagnosis and treatment of neck abscess and mediastinal abscess following esophageal perforation induced by esophageal foreign body]. AB - Objective:The aim of this study is to discuss the clinical presentation, imaging examination and treatment of neck abscess and mediastinal abscess following esophageal perforation induced by esophageal foreign body. Method:Six patients all underwent lateral neck incision and drainage of neck abscess. Simultaneously, mediastinal abscess drainage was performed in 3 cases with mediastinal abscess. Result:All 6 patients were cured. The median time of extraction of gastric tube was 11 days (7-30 days). All patients were not treated with tracheotomy. Conclusion:Neck and chest CT should be done as soon as possible for suspected patients to definite the location of foreign body and the relationship between foreign body and surrounding structures. Patient who were suspected with neck abscess and mediastinal abscess should undergo surgery to remove foreign body and drain the infectious deep neck and mediastinal spaces as early as possible. PMID- 29798509 TI - [The correlation study between PM2.5 and the life quality in patients with allergic rhinitis]. AB - Objective:This study aims to research the relationship betweeen allergic rhinitis (AR) patients life quality and the PM2.5 concentration. Method:Fifty-two patients with clinically diagnosed AR were enrolled in this study. Patients were asked to fill in the questionnaire about the quality of life of rhinoconjunctivitis (RQLQ) continuously. The concentrations of PM2.5 in their living environment were continuously tested for one month (31 days) and SPSS 19.0 software was used to analyze data through descriptive statistical method, Spearman correlation analysis and nonparametric test. P<0.05 was considered statistically significant. Result:There were significant association between PM2.5 and nasal symptoms (r=0.121, P<0.01), daily activities (r=0.146, P<0.01) and practical problems (r=0.099, P<0.01). However, sleep (r=0.059, P=0.051), non-hay fever symptoms (r=0.042, P=0.169), emotion (r=0.042, P=0.168), eye symptoms (r=0.087, P=0.274) and PM2.5 had no statistical significance. AR patients have faced notable differences in genders. The scores of activities, non hay fever symptoms and emotions also showed the difference. Female AR patients have demonstrated the statistical significance with the concentration of PM2.5 among the activity, non hay fever symptoms, practical problems, nasal symptoms and emotions. While the male AR patients existed a statistical significance in the concentration of PM2.5 only between the activity and nasal symptoms. Conclusion:PM2.5 concentration is negatively associated with the life quality of AR patients. The higher concentration of PM2.5, the lower AR patients quality of life they got. PMID- 29798510 TI - [The clinical significance of EBV DNA analysis in nasopharyngeal carcinoma screening]. AB - Objective:The aim of this study is to explore the value of EBV DNA monitor in high risk population of nasopharyngeal carcinoma (NPC). Method:A total of 366 cases of NPC at high risk were screened for 15 864 cases by ELISA, and 262 cases were randomly selected from low-risk groups. Fifty-eight nasopharyngeal carcinoma patients were also involved. EBV DNA was detected by PCR in 366 NPC high risk patients and followed up for 1 year. The clinical significance of EBV-DNA in screening NPC was compared. Result:The positive rate of EBV-DNA test was 12.0% in primary screening, EBV-DNA test in primary screening was 3.4% in low-risk population, and EBV-DNA in nasopharyngeal carcinoma was 91.4%, The positive rate of the three groups was statistically significant (P<0.01); After one year follow up, a total of 267 cases returned visit. Positive rate of group A with continuous high risk was significantly higher than group B who was high risk at the first time of visit and non high risk at returned visit (P<0.05). Conclusion:Quantitative analysis of plasma EBV DNA in high risk population can supply serological risk assessment. It can elevate the efficiency of screening and has significant application value for NPC high risk population. PMID- 29798512 TI - [One case of Pott's puffy tumor: inverted papilloma of nasal sinus postoperative complications]. AB - A 45 years old male patient presented with recurrent abscess of the nasal root and right periorbital tissue. The incision and drainage were performed repeatedly, and anti-infection had poor effect of treatment. Previous history of sinusitis surgery. Nasal cavity and frontal sinus infections and abscesses were treated in other hospitals. CT showed enhanced patchy foci and abscesses on the right temporal side, frontal, periorbital and nasal roots. Repeated discharge of purulent secretions during hospitalization in our hospital prompted Klebsiella pneumoniae infection. After the patient was discharged from the hospital, he was diagnosed with Pott's tumor by repeated consultation with the literature. PMID- 29798511 TI - [A case report of primary ectopic meningioma on occipital subcutaneous soft tissue]. AB - A 65 years old male patient found one lump (A) located in left occipital subcutaneous soft tissue, which was gradually enlarging since thirty years ago. And the patient found another lump (B) located in left shoulder since five years ago. The pathological results showed typical features and immunophenotype of (A) lump resembling intracranial meningothelial meningioma, and (B) lump was a lipoma. No local recurrence or metastasis could been found for 2 months after excision. PMID- 29798513 TI - [Nasal endoscopic treatment in one case of infratemporal fossa hydatid invaded the orbit and skullbase]. AB - PATIENT: male, 43 years old, Tibetan, married. Chief complaint: visual impairment of the left eye for one month. No significant abnormalities observed in nasal endoscopy. Sinus CT: the 47 mm*44 mm cystic low density shadows can be seen in the left infratemporal fossa, which is separated inside, and parts of the lesions have invaded into the orbit and skull base. DIAGNOSIS: the left infratemporal fossa hydatid invaded the orbit and skull base. Under the guidance of general anesthesia navigation, the patient underwent sinusotomy on the left infratemporal fossa and the left eyesight recovered after operation. CT examination showed that the left temporal lobe tumor has been cleared. PMID- 29798514 TI - [Advances in the immune mechanisms of chronic rhinosinusitis]. AB - Chronic rhinosinusitis (CRS) is a common disease of otolaryngology, which has a serious impact on the quality of life of patients. Its pathogenesis is complex and involves in allergic reactions, bacterial and fungal infections, immune dysfunction, impaired epithelial defense, environmental exposure and many other factors. In recent years, a raising attention has been paid to the role of immune mechanism in its pathogenesis; this article is a brief review aimes to the immune mechanism of chronic rhinosinusitis in recent years. PMID- 29798515 TI - [Advances in the research of the relationship between miRNA-29c and cancer]. AB - miRNAs are a class of endogenous non coding, single stranded small RNAs, which regulate the expression of tumor suppressor genes and oncogenes and involve in almost all of the tumor-related processes. miRNA-29c, acting as a tumor suppressor of miRNA, has low expression in many solid malignancies such as nasopharyngeal carcinoma, glioma, gastric cancer, hepatocellular carcinoma, bladder cancer, esophageal cancer, breast cancer, colon cancer and so on. It relates with cancerous proliferation, apoptosis, invasion and metastasis. miRNA 29c directly inhibits the transcription of the target gene encoding protein and down regulates the expression of the target gene. miRNA-29c inhibits tumor cells infinite proliferation and promotes apoptosis by regulating the signal pathways, oncogene, and cell cycle. miRNA-29c can inhibit the invasion and metastasis of tumor cells by regulating different target genes, signal pathways and mediating epithelial-mesenchymal transition. In tumor tissues, the lower expression of miRNA-29c, the higher clinical stage,and the poorer prognosis, so it can be used as an indicator of early diagnosis and prognosis. miRNA-29c is also closely related to head and neck cancer. Therefore, enhancement of the expression of miRNA-29c in tumor cells is expected to be a potential therapeutic strategy for cancer. Selective COX2 inhibitors and demethylated drugs can significantly increase the expression of miRNA-29c. miRNA-29c can be a new tumor biomarker and drug or gene therapeutic target. PMID- 29798517 TI - ? PMID- 29798516 TI - [Advances in the regulation of lncRNA on laryngeal squamous cell carcinoma]. AB - Laryngeal cancer (LC) is one of the most common malignant tumors that occur in the head and neck. Emerging evidence shows that coding RNAs and non-coding RNAs play key roles in the formation and progression of LC. In this review, we focus on the regulation of lncRNAs in LC. LncRNAs appear to be involved in laryngeal cancer growth, invasion, and metastasis and in establishment of the laryngeal tumor microenvironment through various mechanisms. Furthermore, we also discuss the possibilities of establishing lncRNAs as potential biomarkers and therapeutic targets for laryngeal cancer. Taken together, we summarize the emerging roles of lncRNAs in laryngeal cancer development and their possible clinical significance. PMID- 29798518 TI - [Effectiveness of arthroscopic capsular release to treat primary severe frozen shoulder through trans cuff portal]. AB - Objective: To assess the effectiveness of arthroscopic capsular release to treat primary severe frozen shoulder through trans cuff portal. Methods: Between June 2012 and January 2015, 28 patients with primary severe frozen shoulder were enrolled in the study. There were 8 males and 20 females with an average age of 57 years (range, 42-81 years). The left shoulder was involved in 16 cases and the right one in 12 cases. The mean disease duration was 11 months (range, 7-21 months). Six patients had diabetes. All patients underwent arthroscopic capsular release by trans cuff portal. The range of motion (ROM) of the shoulder were measured at preoperation and at 6 weeks and 24 months after operation; the scores of American Shoulder and Elbow Surgeons (ASES) and visual analogue scale (VAS) were used to evaluate the shoulder function and pain. Results: Primary healing of incision was obtained, and no complications of infection, shoulder instability, and nerve injury were found. All patients were followed up 24 months. Pain of the shoulder was obviously relieved; VAS score was significantly lower at 6 weeks and 24 months after operation than preoperation ( P<0.05), and at 24 months than 6 weeks ( P<0.05). ROM of the shoulder and ASES score at 6 weeks and 24 months after operation were significantly increased when compared with preoperative ones ( P<0.05); significant difference was found in ROM of forward flexion and external rotation and the ASES score between at 6 weeks and 24 months ( P<0.05). And internal rotation in-creased from trochanter (9 cases), hip (6 cases), sacrum (7 cases), and L 4 vertebral level (6 cases) before operation to the T 12-T 6 vertebral level at 6 weeks and 24 months after operation, which were close to normal side. Conclusion: Arthroscopic capsular release through trans cuff portal is an effective and safe management for primary severe frozen shoulder. PMID- 29798520 TI - [Comparative study on differences in acetabular position during total hip arthroplasty between by direct anterior approach and by posterolateral approach]. AB - Objective: To compare the differences in acetabular position during total hip arthroplasty (THA) between by direct anterior approach and by posterolateral approach. Methods: Between December 2008 and December 2015, 102 patients undergoing THA were included in the study. THA was performed by anterior approach in 51 cases (anterior group) and by posterolateral approach in 51 cases (posterolateral group). There was no significant difference in gender, age, body mass index, side, and cause of illness between 2 groups ( P>0.05), with comparability. The acetabular abduction angle and anteversion angel were measured on the X-ray film at 1 day after operation to evaluate whether the acetabular prosthesis was displaced in the safe zone. Results: The acetabular abduction angle was (42.28+/-5.77) degrees in the anterior group and was (43.93+/-7.44) degrees in the posterolateral group, showing no significant difference ( t=1.30, P=0.19). The acetabular anteversion angle was (21.14+/-5.17) degrees in the anterior group and was (21.05+/-4.10) degrees in the posterolateral group, showing no significant difference ( t=0.05, P=0.96). The ratio in the target safe zone of the acetabular abduction angle in the anterior group and the posterolateral group were 88.2% (45/51) and 84.3% (43/51) respectively, showing no significant difference ( chi2=0.33, P=0.56). The ratio in the target safe zone of the acetabular anteversion was 80.4% (41/51) in the anterior group and was 82.4% (42/51) in the posterolateral group, showing no significant difference between 2 groups ( chi2=0.06, P=0.79). The ratio in the target safe zone of both the abduction and anteversion angel was 70.6% (36/51) in the anterior group and was 68.6% (35/51) in the posterolateral group, showing no significant difference ( chi2=0.05, P=0.82). Conclusion: There is no differences in the acetabulum position during THA between by direct anterior approach and posterolateral approach. PMID- 29798519 TI - [Effectiveness comparison of suspension fixation plus hinged external fixator and double plate internal fixation in treatment of type C humeral intercondylar fractures]. AB - Objective: To compare the effectiveness of suspension fixation plus hinged external fixator with double plate internal fixation in the treatment of type C humeral intercondylar fractures. Methods: Between January 2014 and April 2016, 30 patients with type C (Association for the Study of Internal Fixation, AO/ASIF) humeral intercondylar fractures were treated. Kirschner wire suspension fixation plus hinged external fixator was used in 14 cases (group A), and double plate internal fixation in 16 cases (group B). There was no significant difference in gender, age, injury cause, disease duration, injury side, and type of fracture between 2 groups ( P>0.05). Results: There was no significant difference in operation time and hospitalization stay between 2 groups ( P>0.05). But the intraoperative blood loss in group A was significantly less than that in group B ( P<0.05); the visual analogue scale (VAS) score at 1 day and 3 days after operation in group A were significantly less than those in group B ( P<0.05). Primary healing of incision was obtained in all patients of 2 groups, and no surgery-related complications occurred. The patients were followed up 6-24 months (mean, 12.3 months) in group A and 6-24 months (mean, 12.8 months) in group B. The self-evaluation satisfaction rate was 85.7% (12/14) in group A and was 81.2% (13/16) in group B at 3 months after operation, showing no significant difference ( chi2=0.055, P=0.990). Based on the improved Gassebaum elbow performance score at 6 months after operation, excellent and good rate of the elbow function was 78.6% (excellent in 5 cases, good in 6 cases, fair in 2 cases, and poor in 1 case) in group A and was 81.2% (excellent in 6 cases, good in 7 cases, fair in 2 cases, and poor in 1 case) in group B, showing no significant difference between 2 groups ( chi2=0.056, P=0.990). Heterotopic ossification occurred at 3 months after operation in 1 case of each group respectively. The X-ray films showed bony union in all cases; no loosening or breakage of screw was observed. The bone union time showed no significant difference between 2 groups ( t=-0.028, P=0.978). The time of internal fixation removal, the intraoperative blood loss, and VAS score at 1 day and 3 days after operation in group A were significant better than those in group B ( P<0.05). Conclusion: The suspension fixation plus hinged external fixator and double plate internal fixation for the treatment of type C humeral intercondylar fractures have ideal outcome in elbow function. But the suspension fixation plus hinged external fixator is better than double plate internal fixation in intraoperative blood loss, postoperative VAS score, and time of internal fixation removal. PMID- 29798521 TI - [Short-term effectiveness of joint distraction by Ilizarov combined with arthroscopic debridement in treatment of knee osteoarthritis]. AB - Objective: To investigate the short-term effectiveness of joint distraction by Ilizarov combined with arthroscopic debridement in the treatment of knee osteoarthritis (KOA). Methods: Between January 2014 and January 2015, 15 patients (15 knees) with KOA were treated using arthroscopic debridement assisting with the Ilizarov distraction technology. There were 7 males and 8 females, aged from 45 to 64 years (mean, 55 years). The left knee and the right knee were involved in 6 and 9 cases respectively. The disease duration was 2.0-9.5 years (median, 6 years). They all had received conservative treatment for 6 months and got poor clinical improvement. The preoperative visual analogue scale (VAS) score, the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, the knee injury and osteoarthritis outcome score (KOOS), the range of motion (ROM) for knee, and the radiographic joint space width were 76.2+/-8.8, 59.3+/-5.7, 44.3+/-7.2, (75+/-21) degrees , and (2.5+/-0.4) mm respectively. According to Kellgren-Lawrence grade system, 11 cases were rated as grade III and 4 cases as grade IV. Results: There was no poor incision healing, infection, and deep vein thrombosis. All the 15 patients were followed up 12-18 months (mean, 15.5 months). Patients achieved pain relief. The knee activity was obviously improved. The postoperative VAS score, WOMAC score, KOOS score, and ROM at 12 months were 20.9+/-7.8, 38.2+/-5.5, 92.1+/-6.9, and (118+/-14) degrees respectively, showing significant difference when compared with preoperative ones ( t=18.213, P=0.000; t=10.317, P=0.000; t=18.564, P=0.000; t=6.599, P=0.000). Postoperative X-ray film showed that joint space width at 12 months was (3.8+/-0.3) mm, showing significant difference when compared with preoperative one ( t=10.070, P=0.000). Conclusion: Joint distraction by Ilizarov combined with arthroscopic debridement can effectively relieve pain, improve the function and quality of life. It was beneficial to cartilaginous tissue repair and delaying the degenerative process of KOA. The short-term effectiveness is satisfactory. PMID- 29798522 TI - [Effect of autologous fibrin clot on tendon-bone healing after anterior cruciate ligament reconstruction]. AB - Objective: To observe the effect and significance of autologous fibrin clot on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction. Methods: Between October 2014 and January 2016, 34 patients (34 knees) with ACL injury were enrolled in the study. During ACL reconstruction, autologous fibrin clot was used in 17 cases (trial group) and was not used in 17 cases (control group). The anterior drawer test, Lachman test, and axial displa-cement test were positive in 2 groups before operation. There was no significant difference in gender, age, causes of injury, injury side, disease cause, and preoperative knee joint activity, Lysholm score, and American Hospital for Special Surgery (HSS) score between 2 groups ( P>0.05), with comparable. The results of anterior drawer test, Lachman test, and axial displacement test were recorded and compared between 2 groups after operation. The knee joint activity, Lysholm score, and HSS score were used to evaluate the knee function recovery at 6, 24, and 48 weeks after operation; the graft signal intensity, graft signal to noise ratio, bone tunnel expansion, and graft tendon-bone node T2 value were measured. Results: All patients were followed up 48 weeks. Surgical incision healed at stage I. No joint infection and joint adhesion occurred. The drawer test, Lachman test, and axial shift test were negative in 2 groups. At 6, 24, and 48 weeks after operation, the Lysholm score of trial group was significantly higher than that of control group ( P<0.05); there was no significant difference in knee joint activity between 2 groups ( P>0.05). The HSS score of trial group was significantly higher than that of control group at 24 and 48 weeks ( P<0.05), but no significant difference was found at 6 weeks ( P>0.05). MRI measu-rement showed that there was significant difference in graft signal intensity, bone tunnel expansion, and graft signal to noise ratio between 2 groups at 6, 24, and 48 weeks after operation ( P<0.05). There was no significant difference in graft tendon-bone node T2 value between 2 groups ( P>0.05) at 48 weeks after operation, but difference was significant at 6 and 24 weeks ( P<0.05). Conclusion: Autologous fibrin clot can effectively enhance graft revascularization, and accelerate the process of tendon-bone healing after ACL reconstruction. PMID- 29798523 TI - [Effectiveness of cerclage and a figure-of-eight tension band by a single titanium wire in treatment of patellar fracture]. AB - Objective: To estimate the outcome of cerclage followed by a figure-of-eight tension band with a single titanium wire for the treatment of patellar fracture. Methods: A retrospective analysis was made on the clinical data of 46 patients with patellar fractures treated between June 2012 and November 2014. There were 30 males and 16 females, aged 20-86 years (mean, 54 years). The fracture causes included falling in 27 cases, traffic accident in 16 cases, and knock in 3 cases. There were 41 cases of closed fractures and 5 cases of open fracture. The injury located at the left side in 24 cases and the right side in 22 cases. According to AO classification, fracture was rated as type 34-A in 3 cases, as type 34-B in 1 case, as type 34-C1 in 7 cases, as type 34-C2 in 13 cases, and as type 34-C3 in 22 cases. The time between injury and operation ranged 1-12 days (mean, 3.7 days). During operations, a single titanium wire was used to pass around the patellar, followed a figure-of-eight wrapping, to tight and fix at the tension of 35 kg. Results: All incisions healed primarily. The patients were followed up 20.6 months on average (range, 6-24 months). Partial wire loosening was found in 2 cases, irritation of skin or soft tissue in 1 case. The X-ray examination showed bony healing at 3 months after operation, without breakage of titanium wire. The internal fixation was removed in 38 cases at 12 months after operation. According to the Bostman rating score, the mean score was 28.34 (range, 24-30) at 12 months after ope-ration; the results were excellent in 42 cases and good in 4 cases, with an excellent and good rate of 100%. Conclusion: For patellar fracture, cerclage followed by a figure-of-eight tension band with a single titanium wire is able to achieve an effective stability and to allow early motion for patient with less complication. PMID- 29798524 TI - [Posterolateral minimal incision, poking reduction, and simple internal fixation in treatment of collapsed fractures of posterolateral tibial plateau]. AB - Objective: To explore the effectiveness of limited incision, poking reduction, and simple internal fixation in the treatment of collapsed fractures of the posterolateral tibial plateau. Methods: Between October 2010 and January 2016, 16 patients with collapsed fractures of the posterolateral tibial plateau underwent posterolateral incision, poking reduction, and simple internal fixation. There were 10 males and 6 females with the age of 22-63 years (mean, 43.5 years). The injury was caused by falling in 5 cases, traffic accident in 7 cases, and falling from height in 4 cases. All cases had closed fractures. The left knee was involved in 9 cases and the right knee in 7 cases. The injury-to-admission time was 2 hours to 3 days (mean, 10 hours). X-ray films showed that the articular surface collapsing was more than 2 mm. According to Schatzker criteria, 6 cases were rated as type II and 10 cases as type III. Twelve cases had fracture of fibular head. The incision length, operation time, intraoperative blood loss, and incision healing were recorded; fracture healing was observed, and tibial plateau angle and posterior slope angle were measured on X-ray films; loss of articular surface reduction was observed by CT scan; and American Hospital for Special Surgery (HSS) score was used to evaluate the knee joint function. Results: The incision length was 7-10 cm (mean, 8.6 cm); operation time was 35-55 minutes (mean, 46 minutes); intraoperative blood loss was 10-35 mL (mean, 28 mL). Primary healing of incision was obtained. Skin pain occurred in 1 case at 2 months because Kirschner wire retracted. Fifteen cases were followed up 8-21 months (mean, 13.5 months). The fracture healing time was from 3 to 6 months (mean, 4.8 months). There was no significant difference in tibial plateau angle and posterior slope angle between at immediate after operation and at last follow-up ( t=-1.500, P=0.156; t=-1.781, P=0.097). The anatomic reduction rate of articular surface was 93.8% (15/16) at immediate after operation. At last follow-up, the recollapse height of articular surface was 0.1-1.2 mm (mean, 0.36 mm). According to the HSS score system, the results were excellent in 12 cases, good in 2 cases, and fair in 1 case, and the excellent and good rate was 93.3%. Conclusion: The limited incision by posterolateral approach, poking reduction, and simple internal fixation have the advantages of small injury, full exposure, and easy operation in the treatment of simple posterolateral tibial plateau fractures; bone graft support and simple internal fixation can prevent recollapse of the articular surface and achieve satisfactory knee function. PMID- 29798525 TI - [Clinical observation of 3.5 mm T support plate fixation for simple posterolateral tibial plateau fracture by posterolateral inverted L-shaped approach]. AB - Objective: To summarize the effectiveness of 3.5 mm T support plate fixation for simple postero-lateral tibial plateau fractures by posterolateral inverted L shaped approach. Methods: Between March 2011 and January 2016, 13 patients with simple posterolateral tibial plateau fracture were treated with 3.5 mm T support plate fixation by posterolateral inverted L-shaped approach. Of 13 cases, 6 were male and 7 were female, aged 28 to 52 years (mean, 43 years). The left side was involved in 5 cases and the right side in 8 cases. The causes of injury were traffic accidents in 6 cases, falls in 3 cases, and falling from height in 4 cases. All of patients had fresh closed fracture by X-ray, CT three dimensional reconstruction, and MRI. According to Schatzker classification, 4 cases were rated as type II and 9 cases as type III. The time between injury and operation was 5-9 days (mean, 7 days). Results: One case had incision skin necrosis, which was cured after debridement and skin grafting; and primary healing was obtained in the other cases. The patients were followed up 10-16 months (mean, 13 months). The X-ray film showed that the fracture line was blurred at 3 months after operation, and disappeared at 12 months after operation. There was no complications of wound infection, major neurovascular injury, loosening or breakage of internal fixation, and dislocation of joint surface. The Hospital for Special Surgery (HSS) knee function score was 94 (range, 89-97) at last follow up; all were excellent. Conclusion: The 3.5 mm T support plate fixation by posterolateral inverted L-shaped approach is one of preferred surgical method for the treatment of simple posterolateral tibial plateau fractures. PMID- 29798526 TI - [Effectiveness comparison of flexible fixation and rigid fixation in treatment of ankle pronation-external rotation fractures with distal tibiofibular syndesmosis]. AB - Objective: To compare the effectiveness of flexible fixation and rigid fixation in the treatment of ankle pronation-external rotation fractures with distal tibiofibular syndesmosis. Methods: A retrospective analysis was made on the clinical data of 50 patients with ankle pronation-external rotation fractures and distal tibiofibular syndesmosis treated between January 2013 and December 2015. Suture-button fixation was used in 23 patients (flexible fixation group) and cortical screw fixation in 27 patients (rigid fixation group). There was no significant difference in age, gender, weight, side, fracture type, and time from trauma to surgery between 2 groups ( P>0.05). The operation time, medial clear space (MCS), tibiofibular clear space (TFCS), tibiofibular overlap (TFO), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Foot and Ankle Disability Index (FADI) score were compared between 2 groups. Results: The operation time was (83.0+/-9.1) minutes in the flexible fixation group and was (79.6+/-13.1) minutes in the rigid fixation group, showing no significant difference ( t=1.052, P=0.265). All patients achieved healing of incision by first intention. The patients were followed up 12-20 months (mean, 14 months). The X-ray films showed good healing of fracture in 2 groups. There was no screw fracture, delayed union or nounion. The fracture healing time was (12.1+/-2.5) months in the flexible fixation group and was (11.3+/-3.2) months in the rigid fixation group, showing no significant difference between 2 groups ( t=1.024, P=0.192). Reduction loss occurred after removal of screw in 2 cases of the rigid fixation group. At last follow-up, there was no significant difference in MCS, TFCS, TFO, AOFAS score and FADI score between 2 groups ( P>0.05). Conclusion: Suture-button fixation has similar effectiveness to screw fixation in ankle function and imaging findings, and flexible fixation has lower risk of reduction loss of distal tibiofibular syndesmosis than rigid fixation. PMID- 29798527 TI - [Neuroprotective effects and mechanism of saikosaponin A on acute spinal cord injury in rats]. AB - Objective: To investigate the effect of saikosaponin a (SSa) on the levels of immune inflammation in rats with acute spinal cord injury and its possible mechanism. Methods: Seventy-two Sprague Dawley rats (weighing, 220-250 g) were randomly divided into sham operation group (group A), spinal cord injury group (group B), and SSa treatment group (group C) respectively, 24 rats in each group. The spinal cord injury model was induced by using the Allen's method in groups B and C; the spinous process and vertebral plate at both sides were cut off by lamina excision to expose the spinal cord in group A. The rats were given intraperitoneal injection of 10 mg/kg SSa in group C and equal volume of normal saline in group B at immediate after injury. The spinal cord tissue was harvested from 18 rats of each group at 24 hours after operation to measure the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) by ELISA, to detect the expressions of nuclear factor kappaB (NF-kappaB) P65, NF-kappaB P-P65, and aquaporin 4 (AQP4) by Western blot and to observe the morphology of spinal cord by HE staining. The motor function of the lower limbs was evaluated by BBB score and tiltboard experiment in 6 rats at 1, 3, 7, 14, 21, and 28 days after injury. Results: The BBB score and tiltboard experiment maximum angle were significantly higher in group A than groups B and C at each time point ( P<0.05) and in group C than group B at 14, 21, and 28 days after operation ( P<0.05). ELISA test showed that the concentrations of TNF-alpha and IL-6 were significantly lower in group A than groups B and C, and in group C than group B ( P<0.05). Western blot results showed that the protein expression levels of NF kappaB P65, NF-kappaB P-P65, and AQP4 were significantly lower in group A than groups B and C, and in group C than group B ( P<0.05). HE staining demonstrated normal neurons of the spinal cord and no obvious lesion in group A; neuronal cells were observed in the injured area of group B, with hemorrhage, neutrophil infiltration, and nerve cell edema in the injured area; the neuronal cells were visible in the spinal cord of group C, with microglia mild hyperplasia, and the pathological changes were improved when compared with group B. Conclusion: SSa has neuroprotective effects on acute spinal cord injury in rats by inhibiting NF kappaB signaling pathway and AQP4 protein expression and reducing inflammation response and edema. PMID- 29798528 TI - [Percutaneous pedicle screw fixation and minimally invasive decompression in the same incision for type A3 thoracolumbar burst fracture]. AB - Objective: To assess the effectiveness of percutaneous pedicle screw fixation and minimally invasive decompression in the same incision for type A3 thoracolumbar burst fracture. Methods: Between May 2014 and February 2016, 43 cases of type A3 thoracolumbar burst fracture with or without nerve symptoms were treated with pedicle screw fixation and neural decompression. Of them, 21 patients underwent percutaneous pedicle screw fixation and minimally invasive decompression in the same incision (percutaneous group), and the other 22 patients underwent traditional open surgery (open group). There was no significant difference in gender, age, cause of injury, fractures level, preoperative American Spinal Injury Association (ASIA) grade, thoracolumbar injury classification and severity (TLICS) score, load-sharing classification, height of injury vertebrae, kyphotic Cobb angle, and spinal canal encroachment between 2 groups ( P>0.05). The length of soft tissue dissection, operation time, intraoperative blood loss, postoperative drainage, X-ray exposure times, and incision visual analogue scale (VAS) score at 1 day after operation were recorded and compared. At last follow up, Japanese Orthopaedic Association (JOA) score and low back pain VAS score were recorded and compared respectively. The ASIA grade recovery was evaluated; the height of injury vertebrae, kyphotic Cobb angle, and spinal canal encroachment were assessed postoperatively. Results: Percutaneous group was significantly better than open group in the length of soft tissue dissection, intraoperative blood loss, postoperative drainage, and incision VAS at 1 day after operation ( P<0.05), but no significant difference was found in operation time between 2 groups ( P>0.05); however, X-ray exposure times of open group were significantly better than that of percutaneous group ( P<0.01). The patients were followed up 12 to 19 months (mean, 15.1 months) in 2 groups. All patients achieved effective decompression. No complications of iatrogenic neurological injury and internal fixation failure occurred. The height of injury vertebrae, kyphotic Cobb angle, and spinal canal encroachment of the fractured vertebral body were significantly improved at 3 days after operation when compared with preoperative ones ( P<0.05), but no significant difference was found between 2 groups ( P>0.05). At last follow-up, JOA score and low back pain VAS score of percutaneous group were significantly better than those of open group ( P<0.05). The neurological function under grade E was improved at least one ASIA grade in 2 groups, but no significant difference was shown between 2 groups ( Z=0.480, P=0.961). Conclusion: Percutaneous pedicle screw fixation and minimally invasive decompression in the same incision for type A3 thoracolumbar burst fracture has satisfactory effectiveness. And it has the advantages of minimal trauma, quick recovery, safeness, and reliableness. PMID- 29798530 TI - [Repair of thumb defects with modified radial dorsal fasciocutaneous flap of thumb]. AB - Objective: To investigate the operative method of repairing soft tissue defect of the thumb with modified radial dorsal fasciocutaneous flap and its effectiveness. Methods: Between June 2015 and December 2016, 15 patients with volar or dorsal defects of the thumb were treated with modified radial dorsal fasciocutaneous flaps which distal pedicles were cut off. Of 15 cases, 11 were male and 4 were female, aged 35-70 years (mean, 46 years). The causes of injury included crush injury in 12 cases and avulsion injury in 3 cases. Because all patients had volar or dorsal defects of the thumb which were accompanied by tendon or bone exposure, they had no condition or desire to replant. There were 12 cases of volar defect of thumb and 3 cases of dorsal defect. The area of defects ranged from 2.0 cm*1.2 cm to 3.0 cm*2.5 cm. The time between injury and operation was 16 hours to 2 days (mean, 30.4 hours). The radial dorsal fascio-cutaneous flaps of 2.3 cm*1.5 cm to 3.3 cm*2.8 cm in size were adopted to repair defects. The donor sites were directly sutured. Results: All flaps survived, and no severe swelling or tension blister occurred. The donor sites and wounds healed by first intention. All patients were followed up 3-12 months (mean, 6 months). The color and texture of the grafted flaps were similar to those of normal skin, with no bloated appearance. According to total active motion standard at last follow-up, the finger function was excellent in 8 cases and good in 7 cases. Conclusion: Modified radial dorsal fasciocutaneous flap of the thumb is a reliable flap with easy dissection and less trauma in repair of soft tissue defects of the thumbs, and satisfactory clinical outcome can be obtained. PMID- 29798529 TI - [Clinical observation of superficial branch of radial artery wrist crease flap for repairing ring tissue defect of fingers]. AB - Objective: To explore the effectiveness and operation method of the superficial branch of radial artery wrist crease flap for repair of ring tissue defect of the fingers. Methods: Between June 2013 and March 2016, the superficial branch of radial artery wrist crease flap was used to repair ring finger tissue defect in 20 cases (21 fingers). There were 14 males and 6 females with an average age of 39.3 years (range, 12-61 years). The causes included machine injury in 9 cases, traffic accident injury in 6 cases, heat inury in 2 cases, and avulsed injury in 3 cases. The index finger was involved in 6 cases, middle finger in 6 cases, ring finger in 3 cases, and little finger in 6 cases. Combined injuries included exposure of bone, tendon, vessel, and nerve. The mean time of injury to operation was 3 hours (range, 0.5-5.5 hours) in 17 patients undergoing emergency operation, and was 8.5 days (range, 7-10 days) in 3 patients undergoing selective operation. The superficial palmar branch of the radial artery from the flap was used for bridging proper digital artery. The donor site was directly sutured in 19 cases and was repaired by skin grafting in 1 case. Results: One case had blood blister at distal flap, which was cured after dressing change; the other flaps survived, and primary healing was obtained. Healing of incision at the donor site healed by first intention. The patients were followed up 6-24 months (mean, 12 months). The appearance, texture, and color of the flaps were satisfactory. The two-point discrimination ranged from 6 to 13 mm (mean, 9 mm) at 6 months after operation. According to the Chinese Medical Association Society of hand surgery of thumb and finger reconstruction function evaluation standard, the results were excellent in 13 cases, good in 4 cases, and fair in 3 cases; the excellent and good rate was 85%. Conclusion: The superficial branch of radial artery wrist crease flap is an ideal choice for the repair of ring tissue defect of the fingers. PMID- 29798531 TI - [Effects of cryopreservation on biological characteristics of tendon-derived stem cells in rat patellar tendon]. AB - Objective: To explore the effects of cryopreservation on the cell survival rate, cell viability, early apoptosis, migration ability, and tendon-related marker expression of tendon-derived stem cells (TDSCs) in rat patellar tendons. Methods: The patellar tendon tissues were harvested from 12 4-month-old male Sprague Dawley rats; 12 patellar tendon tissues from 6 rats were cryopreserved (the experimental group), and the other 12 patellar tendon tissues were not treated (the control group). The patellar tendons were digested with 0.3% type I collagenase to obtain nucleated cells. The survival rate of nucleated cells was detected by trypan blue exclusion assay, and colony-forming ability by crystal violet staining. TDSCs were isolated and cultured to passage 3 (P3). The cell viability of TDSCs was detected by Alamar Blue method, the early apoptosis by Annexin V-FITC/PI assay, the cell migration ability by Transwell method, and the mRNA expressions of tendon-related markers [collagen type I (Col1alpha1), scleraxis (Scx), and tenomodulin (Tnmd)] by real-time quantitative PCR. Results: The survival rate of nucleated cells was 91.00%+/-3.63% in the control group, and was 61.65%+/-4.76% in the experimental group, showing significant difference ( t=12.010, P=0.000). The formation of the primary nucleated cell clones was observed in 2 groups. At 12 days, the number of colonies forming of the experimental group [(8.41+/-0.33)/1 000 nucleated cells] was significantly lower than that of the control group [(15.19+/-0.47)/1 000 nucleated cells] ( t=28.910, P=0.000). The percentage of TDSCs in the active nucleated cells in the experimental group (1.37%+/-0.09%) was significantly lower than that in the control group (1.67%+/-0.10%) ( t=5.508, P=0.003). The growth trend of TDSCs (P3) in the 2 groups was consistent within 14 days. There was no significant difference in absorbance ( A) value between 2 groups at each time point ( P>0.05). The early apoptotic rate of TDSCs was 1.67%+/-0.06% in the experimental group and was 1.63%+/-0.06% in the control group, showing no significant difference ( t=0.707, P=0.519). Under microscope, TDSCs adhered to the lower chamber of the Transwell chamber; the number of cells was 445.00+/-9.70 in the experimental group and was 451.50+/-12.66 in the control group, showing no significant difference ( t=0.998, P=0.342). The relative mRNA expressions of Col1alpha1, Scx, and Tnmd were 3.498+/-0.065, 0.062+/-0.002, and (4.211+/ 0.211)*10 -5 in the experimental group and were 3.499+/-0.113, 0.062+/-0.001, and (4.341+/-0.274)*10 -5 in the con-trol group, showing no significant difference ( t=0.013, P=0.991; t=0.042, P=0.969; t=0.653, P=0.549). Conclusion: The survival rate of nucleated cells in cryopreserved rat tendon tissues is lower, but a large number of active TDSCs, and its cell viability, early apoptosis rate, migration ability in vitro, and cell tenogenic differentiation ability are remained. PMID- 29798532 TI - [Effect of different electrical stimulation waves on orientation and alignment of adipose derived mesenchymal stem cells]. AB - Objective: To investigate the effect of different electrical stimulation waves on orientation and alignment of adipose derived mesenchymal stem cells (ADSCs). Methods: ADSCs were isolated from 5-week-old Sprague Dawley rats (weight, 100-150 g) and cultivated. The cells at passages 3-5 were inoculated to prepare cell climbing slices, subsequently was exposed to direct-current electrical stimulations (ES) at electric field strengths of 1, 2, 3, 4, 5, and 6 V/cm on a homemade electric field bioreactor (groups A1, A2, A3, A4, A5, and A6); at electric field strength of 6 V/cm, at 50% duty cycle, and at frequency of 1 and 2 Hz (groups B1 and B2) of square wave ES; at electric field strength of 6 V/cm, at pulse width of 2 ms, and at frequency of 1 and 2 Hz (groups C1 and C2) of biphasic pulse wave ES; and no ES was given as a control (group D). The changes of cellular morphology affected by applied ES were evaluated by time-lapse micropho-tography via inverted microscope. The cell alignment was evaluated via average orientation factor ( OF). The cytoske-leton of electric field treated ADSCs was characterized by rhodamine-phalloidin staining. The cell survival rates were assessed via cell live/dead staining and intracellular calcium activities were detected by calcium ion fluorescent staining. Results: The response of ADSCs to ES was related to the direct-current electric field intensity. The higher the direct-current electric field intensity was, the more cells aligned perpendicular to the direction of electric field. At each time point, there was no obvious cell alignment in groups B1, B2 and C1, C2. The average OF of groups A5 and A6 were significantly higher than that of group D ( P<0.05), but no significant difference was found between other groups and group D ( P>0.05). The cytoskeleton staining showed that the cells of groups A5 and A6 exhibited a compact fascicular structure of cytoskeleton, and tended to be perpendicular to the direction of the electric field vector. The cellular survival rate of groups A4, A5, and A6 were significantly lower than that of group D ( P<0.05), but no significant difference was found between other groups and group D ( P>0.05). Calcium fluorescence staining showed that the fluorescence intensity of calcium ions in groups A4, A5, and A6 was slightly higher than that in group D, and no significant difference was found between other groups and group D. Conclusion: The direct-current electric field stimulations with physiological electric field strength (5 V/cm and 6 V/cm) can induce the alignment of ADSCs, but no cell alignment is found under conditions of less than 5 V/cm direct-current electric field, square wave, and biphasic pulse wave stimulation. The cellular viability is negatively correlated with the electric field intensity. PMID- 29798534 TI - [Regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism]. AB - Objective: To review the regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism. Methods: The related literature was reviewed. The clinical genetic phenotype, animal experiment, and cell research were illustrated so as to explore the possible regulatory mechanisms. Results: MicroRNA-17-92 cluster is involved in physiological normal organs development, pathological neoplasm occurrence, and development. Recently, studies have shown that microRNA-17-92 cluster constitutes an intricate molecular signaling network with its upstream transcription factors and downstream targeting proteins, which controls bone development, remodeling, and metabolism exquisitely. Conclusion: Present fundamental researches have certain understanding of the regulatory mechanisms of microRNA-17-92 cluster on bone development, remodeling, and metabolism. However, the exact mechanisms under these processes remain unknown. PMID- 29798533 TI - [Sustained release of recombinant human bone morphogenetic protein-2 combined with stromal vascular fraction cells in promoting posterolateral spinal fusion in rat model]. AB - Objective: To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model. Methods: SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and beta-tricalcium phosphate (beta-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/beta-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/beta-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining. Results: The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P<0.05), and in group B than groups A and C ( P<0.05). HE staining, Masson's trichrome staining, and immunohistochemistry staining for OCN staining exhibited a large number of cartilage cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and there was no effective new bone formation in groups A and C. Conclusion: The combination of sustained release of rhBMP-2 and freshly SVFs can significantly promote spinal fusion in rat model, providing a theoretical basis for further clinical applications. PMID- 29798535 TI - [Research progress of the role of periosteum in distraction osteogenesis]. AB - Objective: To review the research progress of the role of periosteum in distraction osteogenesis. Methods: The related domestic and foreign literature about the role of periosteum in distraction osteogenesis in recent years was extensively reviewed, summarized, and the mechanism and influencing factors of periosteum during traction and osteogenesis were analyzed. Results: The periosteum is rich in all kinds of cells (mesenchymal stem cells, osteoblasts, etc.), microvessel and various growth factors, which are necessary for the formation of new bone. It can promote the formation of new bone in the process of traction osteogenesis significantly. Conclusion: The periosteum plays an important role in the progress of distraction osteogenesis. PMID- 29798536 TI - [Research progress of three-dimensional printing technique in foot and ankle surgery]. AB - Objective: To review the current research progress of three-dimensional (3-D) printing technique in foot and ankle surgery. Methods: Recent literature associated with the clinical application of 3-D printing technique in the field of medicine, especially in foot and ankle surgery was reviewed, summarized, and analyzed. Results: At present, 3-D printing technique has been applied in foot and ankle fracture, segmental bone defect, orthosis, corrective surgery, reparative and reconstructive surgery which showed satisfactory effectiveness. Currently, there are no randomized controlled trials and the medium to long term follow-up is necessary. Conclusion: The printing materials, time, cost, medical ethics, and multi-disciplinary team restricted the application of 3-D printing technique, but it is still a promising technique in foot and ankle surgery. PMID- 29798537 TI - [Research progress of correlation between traumatic brain injury and fracture healing]. AB - Objective: To review the current status and advances of the correlation between traumatic brain injury (TBI) and fracture healing. Methods: The related domestic and abroad literature about the correlation between TBI and fracture healing was extensively reviewed and analyzed. Results: There are a variety of studies on the correlation between TBI and fracture healing, which can be divided into two major aspects: revascularization and osteogenesis; the local and systemic changes of the neuropeptide and hormone after TBI. Conclusion: TBI facilitates callus formation, the further research is needed to clarify the exact mechanism. PMID- 29798538 TI - [Early effectiveness of cervical disc replacement by using Pretic-I]. AB - Objective: To observe the early effectiveness of cervical disc replacement with Pretic-I, a new type artificial disc. Methods: A retrospective analysis was made on the clinical data of 10 patients who underwent single segmental cervical disc replacement with Pretic-I from June to December 2014. Among 10 patients, 4 were male and 6 were female, with an average age of 40 years (range, 27-51 years). The mean disease duration was 15.4 months (range, 4-36 months). Affected segments located at C 4, 5 level in 1 case, at C 5, 6 level in 8 cases, and at C 6, 7 level in 1 case. The visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, and neck disability index (NDI) were used to evaluate the clinical outcomes. Besides, the disc height and the range of motion (ROM) at operated level, and ROM of upper and lower adjacent level were measured to assess the function. Results: The operation was successfully completed in all patients who were followed up for 12 months. No complications of aggravated nerve symptoms, vertebral artery injury, esophagotracheal fistula, cerebrospinal fluid leakage, incision infection, hematoma and prosthetic loosening were observed during follow-up. The VAS score, JOA score, and NDI significantly improved at each time point after operation when compared with preoperative scores ( P<0.05). The height of intervertebral disc at operated level was significantly increased at immediate and 3 months after operation when compared with preoperative one ( P<0.05), but no significant difference was found between at 6 months or 12 months after operation and at pre-operation ( P>0.05). No significant difference was shown in the ROM at operated level, and ROM of upper and lower adjacent level between at pre-operation and at each time point after operation ( P>0.05). Conclusion: The early effctiveness of cervical disc replacement using Pretic-I is satisfactory. The symptoms can be relieved significantly and the dynamic features of the operated level, as well as the upper and lower adjacent levels, are well preserved. PMID- 29798539 TI - [Short-term effectiveness of transforaminal unilateral approach for bilateral decompression in lumbar interbody fusion for the treatment of lumbar spinal stenosis]. AB - Objective: To assess the clinical application value of tranforaminal unilateral approach for bilateral decompression by comparing the short-term effectiveness of bilateral decompression via unilateral approach of intervertebral foramen with via small surgical incision of bilateral spinous process in lumbar interbody fusion for the treatment of lumbar spinal stenosis. Methods: Between July 2014 and June 2015, 48 patients with lumbar spinal stenosis underwent decompression and internal fixation by unilateral approach in 24 cases (trial group) and by bilateral small incision approach in 24 cases (control group). There was no significant difference in gender, age, disease duration, disease type, involved segment, combined medical diseases, preoperative level of creatine phosphokinase (CPK), the visual analogue scale (VAS), and Oswestry disability index (ODI) between 2 groups ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage, hospitalization time, and the incidence of complications were recorded. The CPK levels were evaluated at 1, 3, and 7 days after operation. VAS score and ODI were used to evaluate the effectiveness, and lumbar X-ray film or CT scanning to determine the intervertebral bony fusion. Results: There was no significant difference in operation time, intraoperative blood loss, and hospitalization time between 2 groups ( P>0.05), but significant difference was found in postoperative drainage ( t=5.547, P=0.000). At 1 day after operation, the level of CPK in the trial group was significantly lower than that in the control group ( t=3.129, P=0.005), but there was no significant difference at 3 and 7 days after operation between 2 groups ( P>0.05). The patients were followed up 12-24 months (mean, 17 months). All the wounds healed primarily. Heart failure occurred in 1 case of the trial group, and cerebrospinal fluid leakage and pulmonary infection, and nerve root injury occurred in 1 case of the control group respectively. There was no significant difference in the incidence of complications between 2 groups ( chi2=0.273, P=0.602). The interbody fusion rate was 95.8% (23/24) in the trial group and was 91.7% (22/24) in the control group, showing no significant difference ( chi2=0.356, P=0.551). No cage sink, dislocation or plate and screw loosening and breakage was found in 2 groups. No adjacent segment degeneration occurred during the follow-up, and there was no change of scoliosis and lumbar sagittal curvature. At 3, 6, and 12 months after operation, the VAS score and ODI were significantly improved when compared with the preoperative scores in 2 groups ( P<0.05), and the VAS score and ODI of the trial group were significantly better than those of control group ( P<0.05). Conclusion: The bilateral decompression via unilateral approach of intervertebral foramen and small surgical incision of bilateral spinous process in lumbar interbody fusion have satisfactory efficacy for the treatment of lumbar spinal stenosis, but the tranforaminal unilateral approach has the advantages of less trauma, avoidance of bilateral muscle stripping and soft paraspinal muscle injury, retention of posterior spinal structure, faster postoperative recovery, shorter hospital stay and good short-term effectiveness. PMID- 29798540 TI - [Effect of remote controlled injection manipulator system assisted percutaneous kyphoplasty for treatment of rupture of posterior vertebral osteoporotic vertebral fracture]. AB - Objective: To evaluate the effect of remote controlled injection manipulator system (RCIM) assisted percutaneous kyphoplasty (PKP) for the treatment of rupture of posterior vertebral osteoporotic vertebral fracture by comparing with intermittent hand bolus injection of bone cement during operation. Methods: Between September 2010 and January 2016, a retrospective analysis was made on the clinical data of 48 senile patients with single segment rupture of the posterior vertebral osteoporotic thoracolumbar fracture undergoing PKP who accorded with the inclusion criteria. Of 48 patients, 22 received intermittent hand bolus injection of bone cement in the control group, and 26 received RCIM assisted bone cement perfusion in the trial group. There was no significant difference in age, gender, duration of disease, causes of injury, implicated vertebral bodies, bone mineral density T value, pain duration, preoperative visual analogue scale (VAS), relative vertebral body height in the anterior part, and posterior convex Cobb angle between groups ( P>0.05). The bone cement perfusion time, the radiation dose of both doctors and patients, and the amount of bone cement injection were recorded; treatment effects were evaluated based on VAS score, posterior convex Cobb angle, relative ver-tebral body height in the anterior part, ratios of bone cement diffusion area and bone cement leakage rate. Results: The patients were followed up for 6 months; no complications of toxic effect of bone cement, spinal cord or nerve root injuries, infection and vascular embolization occurred during follow-up period. There was no significant difference in bone cement injection amount and radiation dose of doctors between groups ( P>0.05), but bone cement perfusion time, ratios of bone cement diffusion area, and radiation dose of patients were significantly lower in the trial group than the control group ( P<0.05). Bone cement leakage was observed in 6 cases of the control group (27.27%) and 2 cases of the trial group (7.69%), showing significant difference between groups ( chi2=4.850, P=0.029); no cement leakage into the spinal canal was found in both groups. VAS score, relative vertebral body height in the anterior part, and posterior convex Cobb angle were significantly improved at 3 days and 6 months after operation when compared with preoperative ones ( P<0.05), but no significant difference was observed in the above indexes between groups at 3 days and 6 months after operation ( P>0.05). Conclusion: Satisfactory effectiveness can be achieved by applying RCIM assisted PKP for the treatment of rupture of posterior vertebral osteoporotic vertebral fracture. RCIM can shorten perfusion time, reduce radiation dose, and decrease incidence of bone cement leakage. PMID- 29798541 TI - [Efficacy comparison between one-stage combined posterior and anterior approaches and simple posterior approach for lower lumbar tuberculosis]. AB - Objective: To compare the clinical efficacy between one-stage combined posterior and anterior approaches (PA-approach) and simple posterior approach (P-approach) for lower lumbar tuberculosis so as to provide some clinical reference for different surgical procedures of lower lumbar tuberculosis. Methods: A retrospective analysis was made on the clinical data of 48 patients with lower lumbar tuberculosis treated between January 2010 and November 2014. Of them, 28 patients underwent debridement, bone graft, and instrumentation by PA-approach (PA-approach group), and 20 patients underwent debridement, interbody fusion, and instrumentation by P-approach (P-approach group). There was no significant difference in gender, age, course of the disease, and destructive segment between 2 groups ( P>0.05). The operation time, blood loss, bed rest time, visual analogue scale (VAS) and complication were recorded and compared between 2 groups; American Spinal Injury Association (ASIA) grade was used to evaluate the nerve function, Bridwell classification and CT fusion criteria to assess bone fusion, erythrocyte sedimentation rate (ESR) to evaluate the tuberculosis control, and Oswestry disability index (ODI) to estimate lumbar function. Results: The operation time, blood loss, and the bed rest time of the P-approach group were significantly less than those of the PA-approach group ( P<0.05). Iliac vessels rupture was observed in 1 case of the PA-approach group and sinus tract formed in 2 cases of the P-approach group. The patients were followed up 13 35 months (mean, 15.7 months) in the PA-approach group and 15-37 months (mean, 16.3 months) in the P-approach group. At last follow-up, common toxic symptom of tuberculosis disappeared and the ASIA scale was improved to grade E. The VAS score and ESR at 1 year after operation and last follow-up, and ODI at last follow-up were significantly improved when compared with preoperative ones in 2 groups ( P<0.05), but there was no significant difference between the 2 groups ( P>0.05). During follow-up, no internal fixation broken, loosening, or pulling was found. Bridwell bone fusion rates were 89.29% (25/28) and 80.00% (16/20) respectively, and CT fusion rates were 96.43% (27/28) and 90.00% (18/20) respectively, showing no significant difference between the 2 groups ( P>0.05). Conclusion: Both one-stage PA-approach and simple P-approach could obtain good clinical efficacy. The PA-approach should be selected for patients with anterior vertebral destroy, presacral or psoas major muscles abscess, and multiple vertebral body destroy, while P-approach should be selected for patient who could gain a good debridement evaluated by imaging before operation, especially for patients with middle-vertebral body destroy, block the iliac blood vessels and old patients. PMID- 29798542 TI - [Influence of lateral retinacular release on anterior knee pain following total knee arthroplasty]. AB - Objective: To investigate the effect of lateral retinacular release on the clinical outcomes after total knee arthroplasty (TKA) without resurfacing of the patella. Methods: A prospective randomized controlled study was performed on 132 patients with unilateral degenerative knee arthritis undergoing TKA bewteen October 2012 and October 2014, who met the selection criteria. During TKA, lateral retinacular release was used in 66 cases (trial group) and was not used in 66 cases (control group). Two patients were excluded from the study due to missing the follow-up in trial group. Four patients were excluded from the study due to lateral retinacular release in control group. Finally, 64 patients and 62 patients were included in the trial group and in the control group. There was no significant difference in gender, age, body mass index, side, disease duration, preoperative patellar morphology, grading of patellofemoral arthritis, grade of patellar cartilage degeneration, patellar malposition, patellar maltracking, patellar score, and Knee Society Score (KSS) between 2 groups ( P>0.05). The operation time, postoperative drainage volume, hospitalization time, postoperative complications, and patient satisfaction were recorded. Postoperative anterior knee pain was assessed by visual analogue scale (VAS), and the knee joint function was evaluated by KSS score and patellar score. The femoral angle, tibial angle, femoral flexion angle, and tibial posterior slope angle were measured on the X-ray film for postoperative prosthetic alignment. The postoperative patellar tracking and patellar position, as well as the presence of osteolysis, prosthesis loosening, patellar fracture and patellar necrosis were observed. Results: All patients were followed up for 24 months. There was no significant difference in operation time, postoperative drainage volume, hospitalization time, and patient satisfaction between 2 groups ( P>0.05). The incidence of anterior knee pain in the trial group was better than that in the control group ( P=0.033). KSS score and patellar score were significantly improved in both groups at 24 months after operation when compared with preoperative scores ( P<0.05), but no significant difference was found between 2 groups ( P>0.05). Complications included hematoma (2 cases in the trial group, and 1 case in the control group), mild wound dehiscence (2 cases in each group respectively), skin-edge necrosis (1 case in the trial group), and superficial wound infection (1 case in each group respectively), which were cured by conservative treatment. No patellar necrosis, patella fracture, or knee lateral pain occurred in 2 groups. There was no significant difference in complication rate between groups ( P=0.392). Satisfactory implant alignment was observed in both groups during follow-up. There was no significant difference in femoral angle, tibial angle, femoral flexion angle, and tibial posterior slope angle between 2 groups ( P>0.05). No radiolucent line at the bone-implant interface was seen around the tibial components and femoral components in both groups. The patellar maltracking was observed in 3 patients of the trial group and 5 patients of the control group, showing no significant difference ( P=0.488). However, the incidence of patellar malposition in the trial group (18.8%) was significantly lower than that in the control group (35.5%) ( chi2=0.173, P=0.034). Conclusion: Lateral retinacular release during primary TKA without resurfacing of the patella can reduce postoperative knee pain without increasing complications. PMID- 29798543 TI - [Clinical efficacy of arthroscopic simultaneous treatment for anterior cruciate ligament injury combined with meniscus bucket-handle tear]. AB - Objective: To explore the clinical efficacy of arthroscopic simultaneous both anterior cruciate ligament (ACL) reconstruction and suture of the meniscus bucket handle tear (BHT). Methods: Between January 2013 and April 2014, 22 patients (22 knees) with ACL injury and BHT, who accorded with the inclusion criteria, were studied. There were 14 males and 8 females with a mean age of 30.68 years (range, 15-44 years). The left side was involved in 10 cases and the right side in 12 cases. Injury located at the medial meniscus in 14 patients, and at the lateral meniscus in 8 patients. The median of interval from injury to operation was 40 days (range, 9 hours to 4 years). BHT was sutured, and then single bundle reconstruction of ACL was performed under arthroscopy. Results: All incisions healed by first intention, and there were no serious complications such as infection, vascular injury, and nerve injury. The patients were followed up for 26.7 months on average (range, 12-42 months). At 6 weeks after operation, one patient had limited motion of the knee, the function was recovered after release under anesthesia; and one patient had joint space tenderness, which was relieved after conservative treatment. The total effective rate was 90.9% (20/22). At last follow-up, the anterior drawer test, Lachman test, and McMurray test were negative in all the cases. The visual analogue scale (VAS), Tegner activity level score, and Lysholm score were significantly improved at 12 months after operation when compared with preoperative scores ( P<0.05). At 6-12 months after operation, complete healing was obtained in 7 cases, and partial healing in 11 cases, and nonunion in 4 cases based on MRI evaluation criteria by Crues et al. There was no rupture of reconstruc-tive ligament during follow-up. Conclusion: Arthroscopic simultaneous both ACL reconstruction and suture of BHT can improve the symptoms, reduce the risk of re-tear of sutured meniscus effectively, delay degeneration of articular cartilage, and maintain the stability of the knee joint. PMID- 29798544 TI - [Comparative study on screw or buttress plate for fixation of supination adduction type-II medial malleolar fracture]. AB - Objective: To investigate the functional outcomes of buttress plate fixation and simple screws fixation for the treatment of supination-adduction type-II medial malleolar fractures so as to provide reference for selection of internal fixation. Methods: Between March 2009 and December 2012, 53 patients with supination-adduction type-II medial malleolar fractures were treated with open reduction and internal fixation. Of them, buttress plate fixation was used in 30 cases (buttress plate fixation group), and screws fixation was used in 23 cases (screw fixation group). There was no significant difference in age, gender, injury cause, injury side, disease duration, and combined injuries between 2 groups ( P>0.05). Complications and full weight-bearing time were recorded; the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS) were used to evaluate the functional outcomes. Post operative anteroposterior and lateral X-ray films were taken to evaluate fracture reduction and union condition. And the treatment failures were recorded. Results: There was no significant difference in incision related complication rate and infection rate between 2 groups ( P>0.05). The patients were followed up 46-91 months (mean, 64.5 months) in buttress plate fixation group and 44-86 months (mean, 59.5 months) in screw fixation group. The full weight-bearing time of the buttress plate fixation group was significantly shorter than that of screw fixation group ( t=2.05, P=0.04). During follow-up time, malunion and nonunion occurred in 2 cases and 1 case of screw fixation group; anatomic reduction and bony union were observed in the other patients of 2 groups. The union time showed no significant difference between 2 groups ( t=1.06, P=0.30). No significant difference was found in AOFAS score and good and excellent rate, VAS score, operation failure rate, and traumatic osteoarthritis rate between groups ( P>0.05). Conclusion: For patients with supination-adduction type-II medial malleolar fracture, the angle between fracture line and tibial axial line is too small to be fixed firmly with simple screws fixation, with a relatively higher failure rate. And buttress plate fixation can reach rigid fixation, and has better functional outcomes. PMID- 29798545 TI - [Clinical applications of distally based anterolateral thigh flaps based on perforating vessels from lateral circumflex femoral artery oblique branch]. AB - Objective: To explore the feasibility and technical points of soft tissue defect reconstruction of the lower extremity using the distally based anterolateral thigh (dALT) flap based on perforating vessels from the lateral circumflex femoral artery (LCFA) oblique branch. Methods: Between July 2010 and July 2016, 7 patients underwent defect reconstruction of the lower extremities using the dALT flap based on perforating vessels from the LCFA oblique branch. There were 4 males and 3 females with an average age of 26.7 years (range, 3-58 years). The etiologies included angiofibrolipoma in 1 case, malignant fibrous sarcoma in 1 case, soft tissue sarcoma in 1 case, and post-burn scar contracture in 4 cases. The disease duration was 13 years, 1 year, and 8 months in 3 patients with tumors respectively, and was from 6 months to 35 years in 4 patients with post-burn scar contracture. After resection of lesion tissues, the defect size ranged from 8 cm*6 cm to 24 cm*8 cm. The flap size ranged from 9 cm*7 cm to 24 cm*8 cm. The length of the pedicle ranged from 12 to 22 cm (mean, 16.6 cm). The distance from the flap pivot point to the superolateral border of the patella ranged from 9.5 to 14.0 cm (mean, 11.8 cm). The donor sites were directly closed in 6 cases and covered with the split-thickness skin graft in 1 case. Results: All flaps survived after surgery without any major complications. All wounds at the donor and the recipient sites healed primarily. The patients were followed up from 5 to 54 months (mean, 30.7 months). The color, texture, and thickness of the flaps were similar to those of the surrounding skin. No tumor recurrence was observed. The range of motion of flexion and extension of the knee joint were greatly improved in the patients with post-burn scar contracture. Conclusion: For patients who have the oblique branch from the LCFA descending branch which sends out perforating vessels to the skin of the anterolateral thigh region, a dALT flap could be used to reconstruct soft tissue defects of the lower extremities. PMID- 29798546 TI - [Application of digital technology in superficial lateral sural artery perforator flap for tiny hand wounds reconstruction]. AB - Objective: To investigate the effectiveness of the digital technology in repairing tiny hand wounds with superficial lateral sural artery perforator flap. Methods: Between August 2013 and October 2016, 10 cases of tiny hand wounds were treated with the superficial lateral sural artery perforator flap. There were 6 males and 4 females, aged 19 to 47 years (mean, 31.2 years). The causes included crushing injury by machine in 6 cases, traffic accident injury in 3 cases, and electric burning injury in 1 case. The location of the soft tissue defect was the first web in 2 cases, the thumb pulp in 3 cases, the index finger pulp in 1 case, the dorsal palms in 3 cases, and the dorsum of finger in 1 case. The time from injury to hospitalization was 4 hours to 10 days (mean, 3.5 days). The size of wound was from 4 cm*3 cm to 8 cm*7 cm. All defects were associated with exposure of tendon and bone. CT angiography (CTA) from aortaventralis to bilateral anterior and posterior tibial arteries was performed before operation, and the appropriate donor site as well as perforator was selected. Then the CTA data were imported into the Mimics15.0 software to reconstruct the three dimensional structure of the perforator artery, bone, and skin; according to flap size, the flap design and harvesting process were simulated. The flap was obtained on the basis of preoperative design during operation. The size of flaps varied from 5 cm*4 cm to 10 cm*8 cm. The donor site was sutured directly in 9 cases and repaired with skin grafting in 1 case. Results: Superficial medial sural artery peforator was cut in 3 patients whose superficial lateral sural artery was too narrow, and the flaps were obtained to repair defects smoothly in the others. Venous crisis occurred in 1 flap, which survived after exploration of the vessel, thrombus extraction, and thrombolysis; the other flaps survived successfully. All wounds and incisions healed by first intention. All cases were followed up 3-18 months (mean, 10 months). The flaps had good shape. At last follow-up, the results were excellent in 6 cases, good in 3 cases, and fair in 1 case according to total active motion (TAM). Conclusion: The preoperative individualized design of the superficial lateral artery perforator flap can realize through CTA digital technology and Mimics15.0 software; it can reduce the operation risk and is one of better ways to repair the tiny hand wounds. PMID- 29798547 TI - [A biomechanical study on effect of deep radioulnar ligaments on the distal radioulnar joint rotatory stability repaired by bone suture anchors]. AB - Objective: To discuss the role of the bone suture anchors for repair of avulsed deep radioulnar ligaments in maintaining the rotatory stability of the distal radioulnar joint. Methods: Nine upper limbs specimens were selected from fresh adult cadavers to make wrist joint-bone capsular ligaments complex specimen. All the specimens were tested under conditions of intact (normal group), deep radioulnar ligaments injury (injury group), and deep radioulnar ligaments injury repaired with anchoring (repair group). The internal and external rotation torque values were recorded in 45 degrees wrist extension, neutral position, and 45 degrees wrist flexion by AG-IS series MS biomechanical testing system. The statistic software was used to compare difference in rotation torque between groups. Results: In 45 degrees wrist extension, neutral position, and 45 degrees wrist flexion, the internal rotation torque values in normal group were (0.83+/ 0.33), (0.86+/-0.34), and (0.36+/-0.30) N.m respectively; the external rotation torque values were (0.86+/-0.38), (0.44+/-0.22), and (0.25+/-0.21) N.m respectively. The internal rotation torque values in injury group were (0.18+/ 0.17), (0.22+/-0.17), and (0.16+/-0.15) N.m respectively; the external rotation torque values were (0.27+/-0.26), (0.13+/-0.17), and (0.04+/-0.04) N.m respectively. The internal rotation torque values in repair group were (0.79+/ 0.34), (0.73+/-0.33), and (0.41+/-0.23) N.m respectively; the external rotation torque values were (0.80+/-0.39), (0.41+/-0.22), (0.41+/-0.40) N.m respectively. In 45 degrees wrist extension, neutral position, and 45 degrees wrist flexion, the internal and external rotation torque values in injury group were significantly lower than those in normal group and repair group ( P<0.05), but no significant difference was found between repair group and normal group ( P>0.05). Conclusion: The deep radioulnar ligaments are important structure for maintaining rotatory stability of distal radioulnar joint. Bone anchoring of the avulsed deep radioulnar ligaments to the ulna fovea is critically important in reconstructing function anatomy of the distal radioulnar joint. PMID- 29798548 TI - [Effect of different intensity treadmill training on repair of micro-injured Achilles tendon in rats]. AB - Objective: To explore the effect of different intensity treadmill training on the repair of micro-injured Achilles tendon induced by collagenase in rats. Methods: Seventy-two 8-week-old male Sprague Dawley rats (weighing, 200-250 g) were selected. After adaptive treadmill training for 1 week, rats were injected with 30 MUL type I collagenase solution (10 mg/mL) into both Achilles tendons to make micro-injured Achilles tendon models. After 1 week of cage feeding, the rats were randomly divided into 3 groups: the control group, the low-intensity group, and the high-intensity group, 24 rats each group. The rats in control group could move freely, and the rats underwent daily treadmill training at the intensity of 13 m/min and 20 min/d in the low-intensity group and at the intensity of 17 m/min and 60 min/d in the high-intensity group. At immediate, 1 week, and 4 weeks after training, bilateral Achilles tendons were collected from 8 rats of each group for gross observation, histological analysis, and mechanical testing. Results: At immediate after training, there was no significant difference in the gross observation, histological observation, and biomechanical properties of the Achilles tendon between groups ( P>0.05). The gross observation showed connective tissue hyperplasia near Achilles tendon and lackluster tendon in each group at 1 week; hyperplasia significantly reduced in the low-intensity group when compared with the control group, and there were more connective tissue and a large number of neovascularization in the high-intensity group at 4 weeks. At 1 week, there was no significant difference in the semi-quantitative histological total score between groups ( P>0.05), but there were significant differences in vascularity between low-intensity group or high-intensity group and control group ( P<0.05). At 4 weeks, the semi-quantitative histological total score was significantly higher in high-intensity group than control group and low-intensity group ( P<0.05), and in control group than low-intensity group ( P<0.05). There were significant differences in collagen arrangement, cell morphology, abnormal cells, and vascularity between low-intensity group and high-intensity group or control group ( P<0.05). And there was significant difference in abnormal cells between high-intensity group and control group ( P<0.05). The mechanical testing showed that there was no significant difference in cross-sectional area of the Achilles tendon, the ultimate force, tensile strength, and elastic modulus between groups at 1 week ( P>0.05); the low-intensity group was significantly higher than the control group in the ultimate force and the tensile strength ( P<0.05), and than high-intensity group in the ultimate force and elastic modulus ( P<0.05), but no significant difference was found in the other indexes between groups ( P>0.05) at 4 weeks. Conclusion: Low-intensity treadmill training can promote the repair of rat micro-injured Achilles tendon induced by collagenase. PMID- 29798550 TI - [Effects of long time different negative pressures on osteogenic differentiation of rabbit bone mesenchymal stem cells]. AB - Objective: To investigate the effects of long time different negative pressures on osteogenic diffe-rentiation of rabbit bone mesenchymal stem cells (BMSCs). Methods: The rabbit BMSCs were isolated and cultured by density gradient centrifugation. Flow cytometry was used to analyze expression of surface markers. The third passage cells cultured under condition of osteogenic induction and under different negative pressure of 0 mm Hg (control group), 75 mm Hg (low negative pressure group), and 150 mm Hg (high negative pressure group) (1 mm Hg=0.133 kPa), and the negative pressure time was 30 min/h. Cell growth was observed under phase contrast microscopy, and the growth curve was drawn; alkaline phosphatase (ALP) activity was detected by ELISA after induced for 3, 7, and 14 days. The mRNA and protein expressions of collagen type I (COL-I) and osteocalcin (OC) in BMSCs were analyzed by real-time fluorescence quantitative PCR and Western blot. Results: The cultured cells were identified as BMSCs by flow cytometry. The third passage BMSCs exhibited typical long shuttle and irregular shape. Cell proliferation was inhibited with the increase of negative pressure. After induced for 4 days, the cell number of high negative pressure group was significantly less than that in control group and low negative pressure group ( P<0.05), but there was no significant difference between the low negative pressure group and the control group ( P>0.05); at 5-7 days, the cell number showed significant difference between 3 groups ( P<0.05). The greater the negative pressure was, the greater the inhibition of cell proliferation was. There was no significant difference in ALP activity between groups at 3 days after induction ( P>0.05); the ALP activity showed significant difference ( P<0.05) between the high negative pressure group and the control group at 7 days after induction; and significant difference was found in the ALP activity between 3 groups at 14 days after induction ( P<0.05). The greater the negative pressure was, the higher the ALP activity was. Real-time fluorescence quantitative PCR and Western blot detection showed that the mRNA and protein expressions of COL-I and OC protein were significantly higher in low negative pressure group and high negative pressure group than control group ( P<0.05), and in the high negative pressure group than the low negative pressure group ( P<0.05). Conclusion: With the increase of the negative pressure, the osteogenic differentiation ability of BMSCs increases gradually, but the cell proliferation is inhibited. PMID- 29798551 TI - [Repair effects of rat adipose-derived stem cells on DNA damage induced by ultraviolet in chondrocytes]. AB - Objective: To explore the DNA repair effect of rat adipose-derived stem cells (ADSCs) on chond-rocytes exposed to ultraviolet (UV) radiation. Methods: ADSCs were isolated and cultured from the inguinal adipose tissue of Sprague Dawley rat by digestion with collagenase type I. ADSCs cell phenotype was assayed with flow cytometry. Multiple differentiation capability of ADSCs at passage 3 was identified with osteogenic and adipogenic induction. The chondrocytes were obtained from rat articular cartilage by digestion with collagenase type II and were identified with toluidine blue staining. The chondrocytes at passage 3 were irradiated with 40 J/m 2 UV and cultured with normal medium (irradiated group), and medium containing the ADSCs supernatant (ADSCs supernatant group) or ADSCs was used for co-culture (ADSCs group) for 24 hours; no irradiation chondrocytes served as control group. The cell proliferation was estimated by MTS method. The expression of phosphorylated histone family 2A variant (gammaH2AX) was detected by immunofluorescence and Western blot. Results: ADSCs presented CD29(+), CD44(+), CD106(-), and CD34(-); and results of the alizarin red staining and oil red O staining were positive after osteogenic and adipogenic induction. Cell proliferation assay demonstrated the absorbance ( A) values were 2.20+/-0.10 (control group), 1.34+/-0.04 (irradiated group), and 1.57+/-0.06 (ADSCs supernatant group), showing significant difference between groups ( P<0.05). Immunofluorescence and Western blot showed that the gammaH2AX protein expression was significantly increased in irradiated group, ADSCs supernatant group, and ADSCs group when compared with control group ( P<0.05), and the expression was significantly decreased in ADSCs supernatant group and ADSCs group when compared with irradiated group ( P<0.05), but no significant difference was found between ADSCs supernatant group and ADSCs group ( P>0.05). Conclusion: ADSCs can increase the cell proliferation and down-regulate the gammaH2AX protein expression of irradiated cells, indicating ADSCs contribute to the repair of irradiated chondrocyte. PMID- 29798549 TI - [In vitrodifferentiation of human amniotic mesenchymal stem cells into ligament fibroblasts after induced by transforming growth factor beta 1 and vascular endothelial growth factor]. AB - Objective: To investigate whether human amniotic mesenchymal stem cells (hAMSCs) have the characteristics of mesenchymal stem cells (MSCs) and the differentiation capacity into ligament fibroblasts in vitro. Methods: The hAMSCs were separated through trypsin and collagenase digestion from placenta, the phenotypic characteristics of hAMSCs were detected by flow cytometry, the cytokeratin-19 (CK 19) and vimentin expression of hAMSCs were tested through immunofluorescence staining. The hAMSCs at the 3rd passage were cultured with L-DMEM/F12 medium containing transforming growth factor beta 1 (TGF-beta 1) and vascular endothelial growth factor (VEGF) as the experimental group and with single L DMEM/F12 medium as the control group. The morphology of hAMSCs was observed by inverted phase contrast microscope; the cellular activities and ability of proliferation were examined by cell counting kit-8 (CCK-8) method; the ligament fibroblasts related protein expressions including collagen type I, collagen type III, Fibronectin, and Tenascin-C were detected by immunofluorescence staining; specific mRNA expressions of ligament fibroblasts and angiogenesis including collagen type I, collagen type III, Fibronectin, alpha-smooth muscle actin (alpha SMA), and VEGF were measured by real-time fluorescence quantitative PCR. Results: The hAMSCs presented monolayer and adherent growth under inverted phase contrast microscope; the flow cytometry results demonstrated that hAMSCs expressed the MSCs phenotypes; the immunofluorescence staining results indicated the hAMSCs had high expression of the vimentin and low expression of CK-19; the hAMSCs possessed the differentiation ability into the osteoblasts, chondroblasts, and lipoblasts. The CCK-8 results displayed that cells reached the peak of growth curve at 7 days in each group, and the proliferation ability in the experimental group was significantly higher than that in the control group at 7 days ( P<0.05). The immunofluorescence staining results showed that the expressions of collagen type I, collagen type III, Fibronectin, and Tenascin-C in the experimental group were significantly higher than those in the control group at 5, 10, and15 days after culture ( P<0.05). The real-time fluorescence quantitative PCR results revealed that the mRNA relative expressions had an increasing tendency at varying degrees with time in the experimental group ( P<0.05). The relative mRNA expressions of collagen type I, collagen type III, Fibronectin, alpha-SMA, and VEGF in the experimental group were significantly higher than those in the control group at the other time points ( P<0.05), but no significant difference was found in the relative mRNA expressions of collagen type I, collagen type III, and VEGF between 2 groups at 5 days ( P>0.05). Conclusion: The hAMSCs possesses the characteristics of MSCs and good proliferation ability which could be chosen as seed cell source in tissue engineering. The expressions of ligament fibroblasts and angiogenesis related genes could be up-regulated, after induction in vitro, and the synthesis of ligament fibroblasts related proteins could be strengthened. In addition, the application of TGF-beta 1 and VEGF could be used as growth factors sources in constructing tissue engineered ligament. PMID- 29798552 TI - [Effect of porcine small intestinal submucosa extracellular matrix in promoting vitality and functional gene expression of hepatocyte]. AB - Objective: To investigate the effect of porcine small intestinal submucosa extracellular matrix (PSISM) on the vitality and gene regulation of hepatocyte so as to lay the experimental foundation for the application of PSISM in liver tissue engineering. Methods: The experiment was divided into two parts: 1 BRL cells were cultured with 50, 100, and 200 MUg/mL PSISM-medium which were prepared by adding PSISM into the H-DMEM-medium containing 10%FBS in groups A1, B1, and C1, and simple H-DMEM-medium served as a control (group D1); 2 BRL cells were seeded on 1%, 2%, and 3% PSISM hydrogel which were prepared by dissolving PSISM in sterile PBS solution containing 0.1 mol/L NaOH in groups A2, B2, and C2, and collagen type I gel served as a control (group D2). At 1, 3, and 5 days after culture, the morphology and survival of liver cells were detected by the Live/Dead fluorescent staining. The cell vitality was tested by cell counting kit 8 (CCK-8) assay. And the relative expressions of albumin (ALB), cytokeratin 18 (CK18), and alpha-fetoprotein (AFP) in hepatocytes were determined by real-time fluorescent quantitative PCR (RT-qPCR). Results: The Live/Dead fluorescent staining showed the cells survived well in all groups. CCK-8 results displayed that the absorbance ( A) value of group C1 was significantly higher than that of group D1 at 5 days after culture with PSISM-medium, and there was no significant difference between groups at other time points ( P>0.05). After cultured with PSISM hydrogels, the A values of groups A2, B2, and C2 were significantly higher than those of group D2 at 3 and 5 days ( P<0.05), the A value of group A2 was significantly higher than that of groups B2 and C2 at 5 days ( P<0.05), but there was no significant difference between groups at other time points ( P>0.05). RT qPCR showed that the relative expressions of ALB and CK18 mRNA significantly increased and the relative expression of AFP mRNA significantly decreased in groups A1, B1, and C1 when compared with group D1 ( P<0.05). The relative expression of CK18 mRNA in group C1 was significantly lower than that in groups A1 and B1 ( P<0.05). The relative expressions of ALB and CK18 mRNA were significantly higher and the relative expression of AFP mRNA was significantly lower in groups A2, B2, and C2 than group D2 ( P<0.05); the relative expression of CK18 mRNA in group A2 was significantly higher than that in group B2 ( P<0.05), and the relative expression of AFP mRNA in group A2 was significantly lower than that in group C2 ( P<0.05), but no significant difference was found between other groups ( P>0.05). Conclusion: PSISM has good compatibility with hepatocyte and can promote the vitality and functional gene expression of hepatocyte. PSISM is expected to be used as culture medium supplement or cell carrier for liver tissue engineering. PMID- 29798553 TI - [Classification, diagnosis, and treatment system of posteromedial structure and posterolateral corner injury in knee dislocation]. AB - Objective: To review the research progress of diagnosis and treatment system for knee dislocation (KD) based on the stage and classification of posteromedial structure and posterolateral corner injury, so as to provide guidance for clinical work. Methods: The relevant literature on the classification, diagnosis and treatment was extensively reviewed. Results: At present, the criterion of the stage and classification of KD mainly include classification based on the size of the injury energy, Kennedy classification, and the improved Schenck classification, but they are not perfect because of no stage and classification of multiple ligament injury and no standardized treatment of different injuries. Hua Xi Knee Dislocation and Multiple Ligament Injury (HX-KDMLI) has optimum plan for injury treatment of posteromedial structure and posterolateral corner injury in KD based on stage and classification. Conclusion: At present, there is no unified opinion on stages and classifications of the posteromedial structure and posterolateral corner injury in KD as well as on diagnosis and treatment. HX KDMLI has certain feasibility for the stage and classification of the posteromedial structure and posterolateral corner injury in KD, to a certain extent, it can be used as reference for the diagnosis and treatment of KD. PMID- 29798554 TI - [Research progress of larger flexion gap than extension gap in total knee arthroplasty]. AB - Objective: To summarize the progress of larger flexion gap than extension gap in total knee arthro-plasty (TKA). Methods: The domestic and foreign related literature about larger flexion gap than extension gap in TKA, and its impact factors, biomechanical and kinematic features, and clinical results were summarized. Results: During TKA, to adjust the relations of flexion gap and extension gap is one of the key factors of successful operation. The biomechanical, kinematic, and clinical researches show that properly larger flexion gap than extension gap can improve both the postoperative knee range of motion and the satisfaction of patients, but does not affect the stability of the knee joint. However, there are also contrary findings. So adjustment of flexion gap and extension gap during TKA is still in dispute. Conclusion: Larger flexion gap than extension gap in TKA is a new joint space theory, and long-term clinical efficacy, operation skills, and related complications still need further study. PMID- 29798555 TI - [Progress of diagnosis and treatment of ankle fractures combined with acute deltoid ligament injury]. AB - Objective: To review the diagnosis and treatment of ankle fractures combined with acute deltoid ligament injury. Methods: Recent literature concerning the diagnosis and treatment of ankle fractures combined with acute deltoid ligament injury was reviewed. Results: Misdiagnosis is common for ankle fractures combined with acute deltoid ligament injury. A diagnosis is given based on patients' complaints, symptoms, and imaging examination, even surgical exploration is necessary. Whether to repair the deltoid ligament remains controversial. Conclusion: Deltoid ligament is an important structure to stabilize the medial ankle joint. However, treatment of different kinds of ankle fractures combined with acute deltoid ligament injury should be standardized; whether or not repair deltoid ligament is determined by the intraoperative ankle stability. PMID- 29798556 TI - [Effectiveness of multiple small-diameter drilling decompression combined with hip arthroscopy for early osteonecrosis of the femoral head]. AB - Objective: To evaluate the effectiveness of multiple small-diameter drilling decompression combined with hip arthroscopy for early oeteonecrosis of the femoral head (ONFH). Methods: Between March 2010 and December 2013, 91 patients with early ONFH were treated with the operation of multiple small-diameter drilling decompression combined with hip arthroscopy in 39 cases (53 hips, group A) or with drilling decompression alone in 52 cases (74 hips, group B). The patients in 2 groups had obvious hip pain and limited motion before operation. There was no significant difference in gender, age, etiology, effected side, stage of osteonecrosis, and preoperative Harris score between 2 groups ( P>0.05). Results: All operations succeeded and all incisions healed by first intention. The operation time was significantly longer in group A [(73.3+/-10.6) minutes] than in group B [(41.5+/-7.2) minutes] ( t=8.726, P=0.000). Temporary of sciatic nerve apraxia after operation occurred in 2 patients of group A, and no complication occurred in other patients. Patients were followed up 24-52 months (mean, 39.3 months) in group A and 24-48 months (mean, 34.6 months) in group B. At last follow-up, the Harris scores were 83.34+/-8.76 in group A and 76.61+/ 9.22 in group B, showing significant differences when compared between 2 groups ( t=-4.247, P=0.029) and when compared with preoperative values in 2 groups ( t= 10.327, P=0.001; t=-8.216, P=0.008). X-ray films showed that the collapse of the femoral head was observed in 6 hips (1 hip at stage Iand 5 hips at stage II) in group A, and in 16 hips (4 hips at stageIand 12 hips at stage II) in group B; and hip arthroplasty was performed. The total effective rates were 88.68% (47/53) in group A and 78.38% (58/74) in group B, respectively; showing significant difference between 2 groups ( chi2=5.241, P=0.041). Conclusion: Multiple small diameter drilling decompression combined with hip arthroscopy is effective in pain relief, improvement of hip function, slowing-down the process of femoral head necrosis, delaying the need for total hip arthroplasty in patients with early ONFH. PMID- 29798557 TI - [Mid-term effectiveness of total hip arthroplasty by direct anterior approach]. AB - Objective: To retrospectively compare the mid-term effectiveness between by direct anterior approach (DAA) and by posterolateral approach in total hip arthroplasty (THA). Methods: Between January 2009 and December 2010, 110 patients (110 hips) treated with THA and followed up more than 5 years were chosen in the study. THA was performed on 55 patients by DAA (DAA group), and on 55 patients by posterolateral approach (PL group). There was no significant difference in gender, age, body mass index, types of hip joint disease, and preoperative Harris score between 2 groups ( P>0.05). The operation time, amount of bleeding, length of hospital stay, postoperative complications, and the Harris scores were recorded and compared. Results: There was no significant difference in operation time and length of hospital stay between 2 groups ( t=0.145, P=0.876; t=1.305, P=0.093). The amount of bleeding was significantly less in DAA group than in PL group ( t=2.314, P=0.032). All patients were followed up 5-7 years (mean, 5.97 years). Complications happened in 5 cases (9.1%) of DAA group and in 3 cases (5.5%) of PL group, and there was no significant difference in the incidence of complications between 2 groups ( chi2=0.539, P=0.463). There was significant difference in Harris scores at 6 months after operation between 2 groups ( t=2.296, P=0.014), but no significant difference was found in Harris score at 1 year and 5 years between 2 groups ( t=1.375, P=0.130; t=0.905, P=0.087). Further analysis, at 6 months after operation, the joint function score in DAA group was significantly higher than that in PL group ( t=1.087, P=0.034), while there was no significant difference in the pain score and range of motion score between 2 groups ( t=1.872, P=0.760; t=1.059, P=0.091). Conclusion: THA by DAA has the advantages of less bleeding and faster recovery. The short-term effectiveness is superior to the THA by traditional posterolateral approach, but there is no obvious advantage in the mid-term effectiveness. PMID- 29798558 TI - [Short-term effectiveness analysis of one-stage bilateral total hip arthroplasty by direct anterior approach]. AB - Objective: To compare the effectiveness of one-stage bilateral total hip arthroplasty by direct anterior approach (DAA) and by posterolateral approach, and to investigate the application value of DAA in one-stage bilateral total hip arthroplasty. Methods: The clinical data of 65 patients who underwent one-stage bilateral total hip arthroplasty by DAA or posterolateral approach between June 2010 and November 2015 were analyzed retrospectively. DAA was used in 34 cases (group A) and posterolateral approach was used in 31 cases (group B). There was no significant difference in the gender, age, body mass index, preoperative hemoglobin level, etiology, disease duration, preoperative Harris score, and preoperative visual analogue scale (VAS) score between 2 groups ( P>0.05) with comparability. The incision length, operation time, intraoperative blood loss, total blood transfusion volume, hospitalization time, early postoperative complications, Harris score, and VAS score were recorded and compared between 2 groups. The simple Likert scale method was applied to evaluate the patient satisfaction, and the imaging evaluation was used. Results: The incision length, operation time, intraoperative blood loss, total blood transfusion volume, and hospitalization time of group A were significantly less than those of group B ( P<0.05). The patients were followed up 15-48 months (mean, 25.3 months) in group A and 12-51 months (mean, 27.6 months) in group B. The overall incidence of complications related to surgery in group A (10.29%) was significantly lower than that of group B (19.35%) ( chi2=8.769, P=0.023). The acetabular anteversion and abduction angle were in the normal range of 2 groups except 1 hip (1.47%) of group A had a higher acetabular anteversion than normal value. Unstable fixed prosthesis happened in 1 hip of groups A and B respectively, and the remaining femoral calcar had no obvious bone resorption and fixed stably. The Harris score and VAS score at each time point after operation of 2 groups were significantly improved when compared with preoperative scores ( P<0.05), and the differences between the time points after operation were also significant ( P<0.05). The Harris score at 1 and 3 months after operation and the VAS score at 3 days after operation of group A were significantly better than those of group B ( P<0.05), but no significant difference was found at last follow-up between 2 groups ( P>0.05). According to the simple Likert scale method to analyze patient satisfaction, comprehensive satisfaction of group A (97.1%, 33/34) was significantly higher than that of group B (67.7%, 21/31) ( chi2=10.343, P=0.001). Conclusion: The application of DAA in one-stage bilateral total hip arthroplasty can significantly relieve the pain, accelerate the recovery of hip joint function, and improve the patient satisfaction. But in clinical application, more attentions should be paid to strictly grasp the indications and prevent the early complications. The long-term effectiveness needs to be further observed. PMID- 29798559 TI - [Effectiveness analysis of surgical treatment of ipsilateral femoral neck fracture and subtrochanteric fracture]. AB - Objective: To discuss the effectiveness of intramedullary nail fixation with selective cable wiring in the treatment of ipsilateral femoral neck fracture and subtrochanteric fracture. Methods: Between June 2012 and December 2015, a total of 19 patients with ipsilateral femoral neck fracture and subtrochanteric fracture underwent closed reduction of femoral neck fracture and intramedullary nail fixation combined with selective cable wiring. There were 5 males and 14 females with a median age of 52 years (range, 35-77 years). The cause of injury included traffic accident injury in 17 cases and falling injury in 2 cases. According to Garden classification for femoral neck fractures, 7 cases were rated as type II, 8 as type III, and 4 as type IV. Femoral subtrochanteric fractures were classified by Seinsheimer classification, with 9 cases as type II, 5 as type III, 3 as type IV, and 2 as type V. The interval from injury to operation ranged from 2 to 7 days with an average of 3.7 days. Results: The operation time was 58 125 minutes (mean, 82.4 minutes) and the intraoperative blood loss was 225-725 mL (mean, 289.5 mL). All incisions achieved healing by first intention and no early complication such as infection was observed. All patients were followed up 12-18 months (mean, 13.9 months). At 1 month after operation, the tip apex distance was 9-23 mm (mean, 15.2 mm). All patients achieved bone union with the healing time of 18-42 weeks (mean, 27.4 weeks). One case of hip varus and femoral neck re displacement (femoral neck shaft angle was 122 degrees ) occurred at 3 months after operation, which achieved bone union at 42 weeks after operation. Five patients complained of postoperative pain with the visual analogue scale (VAS) score of 1-3 (mean, 1.8), which did not influence normal life. A total of 16 patients recovered preoperative hip function. During follow-up, no fracture nonunion, femoral head necrosis, implant failure, screw cut-out, and loosening of cable wiring was observed. The Harris hip score (HSS) was 72-92 (mean, 82.8) at last follow-up and 15 patients (78.9%) achieved good hip function. Conclusion: Intramedullary nail fixation combined with selective cable wiring was effective in the treatment of ipsilateral femoral neck fracture and subtrochanteric fracture. PMID- 29798560 TI - [Effect of continuous and single shot adductor canal blocks for postoperative analgesia and early rehabilitation after total knee arthroplasty]. AB - Objective: To compare the analgesia effect and clinical rehabilitation between continuous adductor canal block (ACB) and single shot ACB in total knee arthroplasty (TKA).. Methods: Between October 2016 and February 2017, 60 patients with severe knee osteoarthritis undergoing primary unilateral TKA were prospectively recruited in the study. All the patients were randomly allocated into 2 groups and received ultrasound-guided continuous ACB (group A, n=30) or single shot ACB (group B, n=30), respectively. There was no significant difference in gender, age, body mass index, nationality, American Society of Anesthesiology (ASA) grading, and preoperative knee range of motion and quadriceps strength between 2 groups ( P>0.05). After operation, the tourniquet time, postoperative drainage volume, hospitalization time, and adverse events in 2 groups were recorded. Visual analogue scale (VAS) scores at rest and during activity, the quadriceps strength, the knee range of motion, and the time of 90 degrees knee flexion in 2 groups were also recorded and compared. Results: There was no significant difference in tourniquet time, postoperative drainage volume, and incidence of adverse events between 2 groups ( P>0.05). But the hospitalization time was significant shorter in group A than in group B ( P<0.05). VAS scores at rest and during activity were lower in group A than in group B, with significant differences in VAS score at rest after 12 hours and in VAS score during activity after 8 hours between 2 groups ( P<0.05). The quadriceps strength was higher in group A than in group B, with significant difference at 24, 48, and 72 hours ( P<0.05). The knee range of motion was significantly better in group A than in group B at 24, 48, 72 hours and on discharge ( P<0.05). The time of 90 degrees knee flexion was significantly shorter in group A than in group B ( t=-2.951, P=0.016). There were 4 patients in group A and 7 patients in group B requiring meperidine hydrochloride (50 mg/time) within 24 hours, and 3 patients in group A and 7 patients in group B at 24 to 48 hours, and 1 patient in group A and 3 patients in group B at 48 to 72 hours. Effusion in the catheter site occurred in 2 cases of group A, but no catheter extrusion occurred. Conclusion: Continuous ACB is superior in analgesia both at rest and during activity and opioid consumption compared with single shot ACB after TKA. And the quadriceps strength could be reserved better in continuous ACB group, which can perform benefits in early rehabilitation. PMID- 29798561 TI - [Short-term effectiveness of bone cement combined with screws for repairing tibial plateau defect in total knee arthroplasty]. AB - Objective: To summarize the effectiveness of bone cement combined with screws for repairing tibial plateau defect in total knee arthroplasty (TKA). Methods: Between March 2013 and March 2016, 30 patients were treated with TKA and bone cement combined with screws for repairing tibial plateau defect. Of the 30 patients, 8 were male and 22 were female, with an average age of 64.7 years (range, 55-71 years). And 17 cases were involved in left knees and 13 cases in right knees; 22 cases were osteoarthritis and 8 cases were rheumatoid arthritis. The disease duration ranged from 9 to 27 months (mean, 14 months). Knee Society Score (KSS) was 41.63+/-6.76. Hospital for Special Surgery Knee Score (HSS) was 38.10+/-7.00. The varus deformity of knee were involved in 19 cases and valgus deformity in 11 cases. According to the Rand classification criteria, tibial plateau defect were rated as type IIb. Results: All incisions healed by first intention, without infection or deep vein thrombosis. All the patients were followed up 27.5 months on average (range, 10-42 months). At last follow-up, HSS score was 90.70+/-4.18 and KSS score was 93.20+/-3.75, showing significant differences when compared with preoperative values ( t=-58.014, P=0.000; t= 60.629, P=0.000). Conclusion: It is a simple and safe method to repair tibial plateau defect complicated with varus and valgus deformities with bone cement and srews in TKA. PMID- 29798562 TI - [Combination Ilizarov technique with tibiotalar or tibiocalcanean arthrodesis for one-stage treatment of ankle joints infection and bone defects]. AB - Objective: To evaluate the effectiveness of Ilizarov technique and tibiotalar or tibiocalcanean arthrodesis for one-stage treatment of ankle joints infection and bone defects. Methods: Between January 2014 and April 2016, 14 patients with ankle joints infection and bone defects were treated by Ilizarov technique and tibiotalar or tibiocalcanean arthrodesis for one-stage. There were 12 males and 2 females with an average age of 39.8 years (range, 25-61 years). The causes of ankle infection included falling from height injury in 5 cases, falling injury in 4 cases, traffic accident injury in 1 case, crushing injury in 1 case, sprain injury in 1 case, and hematogenous reason in 2 cases. All the patients received surgery for 0-8 times (mean, 3.7 times) before admission. The modified American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was 30.25+/ 3.54 before operation. The disease duration was 1-30 months (mean, 10.3 months). Results: All the incisions healed by first intension without recurrence of infection, and two-stage bone grafting operation did not performed. One case felt slight local pain and swell of ankle joint after weight-bearing walking more than 30 minutes, and without special treatment. All the patients had different degree skin redness and swelling of Kirschner wire pinhole for 0-3 times, and relieved after symptomatic treatment. All the patients were followed up 6-27 months (mean, 16.8 months). Except for 2 cases who did not remove the external fixator (with external fixation time of 6 months and 8 months respectively), the other patients removed the external fixator at 6-14 months (mean, 9 months) after operation, all patients recovered the walk function and without ankle pain. The modified AOFAS ankle and hindfoot score after removal of external fixator (70.92+/-1.0) was significantly higher than preoperative one ( t=-10.992, P=0.000). Conclusion: It is a simple and effective method for one-stage treatment of ankle joints infection and bone defects by Ilizarov technique and tibiotalar or tibiocalcanean arthrodesis. PMID- 29798563 TI - [Effectiveness analysis of induced membrane technique in the treatment of infectious bone defect]. AB - Objective: To evaluate the effectiveness of induced membrane technique in the treatment of infectious bone defect. Methods: Thirty-six patients (37 bone lesions) with infectious bone defects were treated with induced membrane technique between January 2011 and June 2014. There were 28 males and 8 females with an average age of 36 years (range, 20-68 years). All bone defects were post traumatic infectious bone defect. The bone defect was located at the tibia and fibula in 24 cases (25 bone lesions), at femurs in 6 cases (6 bone lesions), at ulnas and radii in 2 cases (2 bone lesions), at calcanei in 3 cases (3 bone lesions), and at clavicle in 1 case (1 bone lesion). The average time between onset and the treatment of induced membrane technique was 6.2 months (range, 0.5 36.0 months); 15 patients were acute infections (disease duration was less than 3 months). At the first stage, after the removal of internal fixator (applicable for the patients who had internal fixation), complete debridement of infection necrotic bone tissue and surrounding soft tissue was performed and the bone defects were filled with antibiotic-impregnated cement spacers. If the bone was unstable after debridement, external fixator or plaster could be used for stabilization. Patients received sensitive antibiotics postoperatively. At the second stage (usually 6-8 weeks later), the cement spacer were removed, with preservation of the induced membrane formed by the spacer, and filled the bone defect with autologous iliac bone graft within the membrane. Results: The hospitalization time after debridement was 17-30 days (mean, 22.2 days), and the hospitalization time after the second stage was 7-14 days (mean, 10 days). All the flaps healed uneventfully in 16 cases treated with local flap transposition or free flap grafting after debridement. One patient of femur fracture received Ilizarov treatment after recurrence of infection at 11 months after operation; 1 patient of distal femoral fracture received amputation after recurrence of infection at 1 month after operation; 1 patient of distal end of tibia and fibula fractures received ankle arthrodesis after repeated debridements due to the recurrence of infection; 1 patient of tibia and fibula fractures lost to follow up. The other 32 patients (33 bone lesions) were followed up 1-5 years (mean, 2 years) without infection recurrence, and the infection control rate was 91.7% (33/36). All the patients had bony union, and the healing time was 4-12 months (mean, 7.5 months); no refracture occurred. One patient of femur bone defect had a lateral angulation of 15 degrees and leg discrepancy of 1.5 cm. Superficial pin infection was observed in 7 cases and healed after intensive wound care and oral antibiotics. Adjacent joint function restriction were observed in 6 cases at last follow-up. Conclusion: Induced membrane technique is a simple and reliable technique for the treatment of infectious bone defect. The technique is not limited to the size of the bone defect and the effectiveness is satisfactory. PMID- 29798564 TI - [Treatment of multiple segments of thoracolumbar tuberculosis using posterior unilateral debridement with bone graft and internal fixation]. AB - Objective: To explore the effectiveness and related issues in the treatment of multiple segments of thoracolumbar tuberculosis through posterior unilateral debridement with bone graft and internal fixation. Methods: The clinical data of 29 patients with multiple segments of thoracolumbar tuberculosis who met the selection criteria were retrospective analyzed between January 2012 and July 2015. There were 17 males and 12 females, with age of 21-62 years (mean, 37.4 years). Lesions contained 3-8 vertebral segments, including 3 segments in 6 cases, 4-6 segments in 17 cases, and 7-8 segments in 6 cases. The center lesions located at thoracic spine in 8 cases, lumbar spine in 10 cases, and thoracolumbar segment in 6 cases, and thoracic lumbar skip lesions in 5 cases. The complications included vertebral abscess in 7 cases, psoas major abscess in 6 cases, sacral spine muscle abscess in 7 cases, iliac fossa and the buttocks abscess in 1 case, spinal canal abscess in 2 cases. Preoperative neurological function was assessed according to the American Spinal Injury Association (ASIA) classification: 1 case of grade B, 3 cases of grade C, 8 cases of grade D, and 17 cases of grade E. The disease duration was 6-48 months (mean, 19.3 months). All the patients were treated with posterior unilateral transpedicular or transarticular debridement with bone graft fusion and internal fixation under general anesthesia. Pre- and post-operative visual analogue scale (VAS) score, Oswestry disability index (ODI), and sagittal Cobb angle were recorded and compared. Bridwell classification standard was used to evaluate bone graft fusion. According to the number and the center of the lesion, the necessity to placement of titanium mesh cage was analyzed. Results: All the patients were followed up 18-30 months (mean, 24 months). Cerebrospinal fluid leakage occurred in 3 cases, intercostal neuralgia in 2 cases, wound unhealed and fistula formation in 1 case, and ofiliac fossa abscess recurred in 1 case, and all recovered after symptomatic treatment. During follow-up, no fracture or loosing of internal fixation was found and all the lesions were cured at last follow-up. According to Bridwell classification standard, bone graft achieved bony fusion during 4-9 months after operation. The VAS score, ODI, and Cobb angle at immediate after operation and at last follow-up were significantly improved when compared with preoperative ones ( P<0.05). At last follow-up, the neural function of all patients improved significantly when compared with preoperative one ( Z= 3.101, P=0.002). The ratio of no placement of titanium mesh cage was significantly higher in patients with more than 6 lesion segments (6/6, 100%) than in patients with less than 6 lesion segments (4/23, 17.4%) ( chi2=14.374, P=0.000). And the ratio of placement of titanium mesh cage was not significantly different between the patients with the different locations of center focus ( chi2=0.294, P=0.863). Conclusion: For treating multiple segments of thoracolumbar tuberculosis, the method of posterior unilateral debridement with bone graft and internal fixation can decrease the damage of posterior spinal structures and surgical trauma. PMID- 29798565 TI - [Treatment of thoracolumbar burst fractures with short-segment pedicle instrumentation and recombinant human bone morphogenetic protein 2 and allogeneic bone grafting in injured vertebra]. AB - Objective: To investigate the effect of preventing the loss of correction and vertebral defects after thoracolumbar burst fractures treated with recombinant human bone morphogenetic protein 2 (rhBMP-2) and allogeneic bone grafting in injured vertebra uniting short-segment pedicle instrumentation. Methods: A prospective randomized controlled study was performed in 48 patients with thoracolumbar fracture who were assigned into 2 groups between June 2013 and June 2015. Control group ( n=24) received treatment with short-segment pedicle screw instrumentation with allogeneic bone implanting in injured vertebra; intervention group ( n=24) received treatment with short-segment pedicle screw instrumentation combining with rhBMP-2 and allogeneic bone grafting in injured vertebra. There was no significant difference in gender, age, injury cause, affected segment, vertebral compression degree, the thoracolumbar injury severity score (TLICS), Frankel grading for neurological symptoms, Cobb angle, compression rate of anterior verterbral height between 2 groups before operation ( P>0.05). The Cobb angle, compression rate of anterior vertebral height, intervertebral height changes, and defects in injured vertebra at last follow-up were compared between 2 groups. Results: All the patients were followed up 21-45 months (mean, 31.3 months). Bone healing was achieved in 2 groups, and there was no significant difference in healing time of fracture between intervention group [(7.6+/-0.8) months] and control group [(7.5+/-0.8) months] ( t=0.336, P=0.740). The Frankel grading of all patients were reached grade E at last follow-up. The Cobb angle and compression rate of anterior verterbral height at 1 week after operation and last follow-up were significantly improved when compared with preoperative ones in 2 groups ( P<0.05). There was no significant difference in Cobb angle and compression rate of anterior verterbral height between 2 groups at 1 week after operation ( P>0.05), but the above indexes in intervention group were better than those in control group at last follow-up ( P<0.05). At last follow-up, there was no significant difference of intervertebral height changes of internal fixation adjacent upper position, injured vertebra adjacent upper position, injured vertebra adjacent lower position, and internal fixation adjacent lower position between 2 groups ( P>0.05). Defects in injured vertebra happened in 18 cases (75.0%) in control group and 5 cases (20.8%) in intervention group, showing significant difference ( chi2=14.108, P=0.000); and in patients with defects in injured vertebra, bone defect degree was 7.50%+/-3.61% in control group, and was 2.70%+/-0.66% in intervention group, showing significant difference ( t=6.026, P=0.000). Conclusion: Treating thoracolumbar fractures with short-segment pedicle screw instrumentation with rhBMP-2 and allogeneic bone grafting in injured vertebra can prevent the loss of correction and vertebral defects. PMID- 29798567 TI - [Evaluation of urogenital sinus surgery in disorder of sex development]. AB - Objective: To explore the indication and effectiveness of urogenital sinus surgery in feminizing genitoplasty of disorder of sex development (DSD). Methods: A retrospective analysis was made on clinical data from 22 patients with DSD who underwent one stage feminizing genitoplasty between October 2010 and December 2015. The patients' age ranged from 1 year and 2 months to 21 years, with the median age of 2 years and 1 month. According to the Prader classification criteria, the appearance of vulvas were rated as grade I in 7 cases, grade II in 6 cases, grade III in 8 cases, and grade IV in 1 case. Cystoscopy was applied before feminizing genitoplasty in all patients. Low confluence of vagina and urethra was found in 19 patients, while high confluence was found in 3 patients. The mean length of urogenital sinus was 1.6 cm (range, 0.5-3.0 cm). The mean length of water-filled vagina was 4.4 cm (range, 3.5-5.5 cm). Cervix was detected at the end of vagina in 16 patients, meanwhile absence of cervix was detected in 6 patients. The same procedures of clitoroplasty and labioplasty were used in all patients. Three procedures of urogenital sinus surgery were applied, as the "cut back" vaginoplasty in 6 patients, the "flap" vaginoplasty in 11 patients, and the partial urogenital sinus mobilization (PUM) in 5 patients. Results: All procedures were completed successfully and the incisions healed by stage I. All patients were followed up 12-74 months, with the average of 30.5 months. The outcome of appearance evaluation was excellent in 13 patients (59.1%), good in 6 patients (27.3%), and poor in 3 patients (13.6%). Urinary incontinence, post-void residual, urinary infection, and urethrovaginal fistula were not found in 17 toilet trained patients. Conclusion: Urogenital sinus surgery is the most critical step in feminizing genitoplasty of DSD. It can be finished in one stage procedure with clitoroplasty and labioplasty before puberty. If thoroughly evaluation before surgery is completed and the principle of different procedures is handled, the outcome will be satisfactory. PMID- 29798566 TI - [Effectiveness comparison between unilateral and bilateral percutaneous kyphoplasty for Kummell disease]. AB - Objective: To compare the effectiveness between unilateral and bilateral percutaneous kyphoplasty (PKP) in the treatment of Kummell disease. Methods: The clinical data of 45 patients with Kummell disease that met the criteria between January 2014 and February 2016 were analyzed retrospectively. Among them, 26 cases were treated by unilateral PKP (unilateral group), 19 cases were treated by bilateral PKP (bilateral group). There was no significant difference in gender, age, disease duration, injured vertebral segment, bone mineral density (T value), and the preoperative visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior vertebral height, and kyphosis Cobb angle between 2 groups ( P>0.05). The operation time, intraoperative fluoroscopy times, amount of injected bone cement, and hospitalization time were recorded, and the situation of bone cement leakage was observed. The VAS score, ODI, anterior vertebral height, and kyphosis Cobb angle were evaluated before operation, at 1 day after operation, and at last follow-up. Results: Bone cement leakage during the operation were found in 4 cases (15.38%) of unilateral group and 3 cases (15.79%) of bilateral group without obvious neurological symptoms; there was no significant difference in the incidence of bone cement leakage between 2 groups ( chi2=0.000, P=1.000). The operation time, intraoperative fluoroscopy times, and amount of injected bone cement in the unilateral group were significantly lower than those in the bilateral group ( P<0.05); but there was no significant difference in the hospitalization time between 2 groups ( P>0.05). The X-ray film examination showed that there was no pulmonary embolism in all patients at 1 day after operation. All the patients were followed up 12-24 months, with an average of 16.4 months. There was no complication such as vertebral re-fracture or cement block displacement in the injured vertebra. The VAS score, ODI, anterior vertebral height, and kyphosis Cobb angle at 1 day after operation and at last follow-up were significantly improved when compared with preoperative values in 2 groups ( P<0.05); the VAS score and ODI in 2 groups were further reduced at last follow-up when compared with the value at 1 day after operation ( P<0.05), but the anterior vertebral height and kyphosis Cobb angle in 2 groups at last follow up did not change significantly ( P>0.05). There was no significant difference in above indexes at 1 day after operation and at last follow-up between 2 groups ( P>0.05). Conclusion: Both unilateral and bilateral PKP can achieve good effectiveness in treatment of Kummell disease. But the unilateral puncture technique possesses advantages such as shorter operation time, less radiation dose, and less amount of injected bone cement. PMID- 29798569 TI - [Repair of large skin defect of upper limb with abdominal pedicled flap]. AB - Objective: To investigate the feasibility and effectiveness of designing wide pedicle of abdominal pedicled flap and repairing large skin defect of upper limb with improved suture method. Methods: Between March 2014 and August 2016, 11 cases with hand and forearm skin soft tissue defect were repaired with abdominal pedicled flaps. Among them, 8 cases were male and 3 were female; aged 18-65 years (mean, 38 years). The causes of injury were machinery injury in 7 cases and traffic accident in 4 cases. The wound located at left upper limb in 6 cases and right upper limb in 5 cases. The size of wound ranged from 12 cm*7 cm to 20 cm*10 cm. The interval from injury to operation was 2-5 days (mean, 4 days). Four cases were repaired with lower abdominal flap and 7 with umbilical flap. The size of flap ranged from 10 cm*9 cm to 22 cm*10 cm. And the flap was designed with wide pedicle at width of 8 to 18 cm (mean, 15 cm); then the wound was sutured with improved method. The pedicle was cut after 3 weeks. Results: All the flaps survived without congestion, necrosis, and tension blisters. The wound and the incision were both healed at stage I. All patients were followed up 4-12 months (mean, 8 months). The skin color, texture, and shape were satisfying, and no ulcer formed. Only line-like scar left at the donor site. Conclusion: Abdominal pedicled flap with wide pedicle and improved suture method can reduce the abdominal skin waste, avoid postoperative infection, and be feasible to repair large skin defect of upper limb with advantages of simple operation and reliable fixation. PMID- 29798568 TI - [Application of serratus anterior muscle flap combined with breast implants for breast reconstruction after modified radical mastectomy]. AB - Objective: To investigate effectiveness of the combination of serratus anterior muscle flap and breast implants for breast reconstruction after modified radical mastectomy. Methods: Between January 2015 and December 2015, 25 female patients with breast cancer were enrolled, aged 24-62 years (mean, 40.6 years). The tumor located at left side in 9 cases and right side in 16 cases; 14 cases were in the left upper quadrant, 4 cases were in the left lower quadrant, 7 cases were on the top of the breast. All cases were invasive ductal carcinoma. According to TNM staging, 14 cases were at stageIand 11 cases were at stageIIA. The diameter of lumps were all less than 3 cm. All those lumps were solitary and without distant metastasis. The sentinel nodes were all negative. After modified radical mastectomy, the breasts were reconstructed by serratus anterior muscle flap and breast implants. The nipples were spared in 22 cases. Results: The operation time was 113-148 minutes (mean, 136 minutes). All breasts survived and incisions healed at stageI. There was no complication such as hematoma, infection, etc. All patients were followed up 6-18 months (mean, 15 months). Except 1 case, the others were evaluated according to the criteria of the reconstructed breast at 12 months after operation. Among them, 23 cases were evaluated as good and 1 case as fair. There was no tumor recurrence during the follow-up period. Conclusion: The combination of serratus anterior muscle flap and breast implants after the modified radical mastectomy is a handy approach of breast reconstruction which is less harmful with few postoperative complications. It also gains a high degree of satisfaction from patients for good breast shape. PMID- 29798570 TI - [Repair of composite tissue defects and functional reconstruction of upper arm with latissimus dorsi Kiss flap]. AB - Objective: To investigate the effectiveness of latissimus dorsi Kiss flap for repairing composite tissue defects and functional reconstruction of upper arm. Methods: Between March 2010 and November 2016, 12 cases of composite tissue defects of upper arm were repaired by latissimus dorsi Kiss flap with blood vessel and nerve bunch. There were 8 males and 4 females with a median age of 34 years (range, 21-50 years). The reason of injury included plowing mechanical injury in 4 cases, traffic accident injury in 5 cases, electrical injury in 2 cases, and resecting upper arm soft tissue sarcoma in 1 case. There were deltoid defect in 5 cases, triceps brachii and brachialis defect in 4 cases, and deltoid, triceps brachii, and brachialis damaged in varying degrees in 3 cases. The defect area ranged from 13 cm*7 cm to 20 cm*8 cm. Among them, there were 6 cases of fracture combined with partial bone exposure, one of them with bone defect. The disease duration was 3 hours to 6 months. The flap size ranged from 10 cm*6 cm to 15 cm*7 cm, and the donor sites were directly sutured. Results: Twelve flaps survived with primary healing of wounds. Ten patients were followed up 6-26 months (mean, 14 months). At last follow-up, the flaps were soft and the skin color was similar to the surrounding skin. No obvious scar was found at donor sites. The abduction range of motion of shoulder was 30-90 degrees . The muscle strength of brachialis were all at grade 4 or above. The superficial sensation and tactile sensation recovered partialy (S 1 in 2 cases, S 2 in 6 cases, S 3 in 2 cases). According to Society of Hand Surgery standard for the evaluation of upper part of the function, the shoulder joint function was excellent in 2 cases, good in 4 cases, and fair in 4 cases. Conclusion: The design of the latissimus dorsi Kiss flaps are flexible, and the donor site can be directly sutured, with the nerves of the latissimus dorsi muscle can partialy reconstruct abduction function of upper arm. In general, the Kiss flap repairing upper arm defect can obtain satisfactory effectiveness. PMID- 29798571 TI - [Construction of injectable tissue engineered adipose tissue with fibrin glue scaffold and human adipose-derived stem cells transfected by lentivirus vector expressing hepatocyte growth factor]. AB - Objective: To discuss the possibility of constructing injectable tissue engineered adipose tissue, and to provide a new approach for repairing soft tissue defects. Methods: Human adipose-derived stem cells (hADSCs) were extracted from the lipid part of human liposuction aspirate by enzymatic digestion and identified by morphological observation, flow cytometry, and adipogenic induction. The hADSCs underwent transfection by lentivirus vector expressing hepatocyte growth factor and green fluorescent protein (HGF-GFP-LVs) of different multiplicity of infection (MOI, 10, 30, 50, and 100), the transfection efficiency was calculated to determine the optimum MOI. The hADSCs transfected by HGF-GFP LVs of optimal MOI and being adipogenic inducted were combined with injectable fibrin glue scaffold, and were injected subcutaneously into the right side of the low back of 10 T-cell deficiency BALB/c female nude mice (transfected group); non HGF-GFP-LVs transfected hADSCs (being adipogenic inducted) combined with injectable fibrin glue scaffold were injected subcutaneously into the left side of the low back (untransfected group); and injectable fibrin glue scaffold were injected subcutaneously into the middle part of the neck (blank control group); 0.4 mL at each point. Twelve weeks later the mice were killed and the implants were taken out. Gross observation, wet weight measurement, HE staining, GFP fluorescence labeling, and immunofluorescence staining were performed to assess the in vivo adipogenic ability of the seed cells and the neovascularization of the grafts. Results: The cultured cells were identified as hADSCs. Poor transfection efficiency was observed in MOI of 10 and 30, the transfection efficiency of MOI of 50 and 100 was more than 80%, so the optimum MOI was 50. Adipose tissue-like new-born tissues were found in the injection sites of the transfected and untransfected groups after 12 weeks of injection, and no new-born tissues was found in the blank control group. The wet-weight of new-born tissue in the transfected group [(32.30+/-4.06) mg] was significantly heavier than that of the untransfected group [(25.27+/-3.94) mg] ( t=3.929, P=0.001). The mature adipose cells in the transfected group [(126.93+/-5.36) cells/field] were significantly more than that in the untransfected group [(71.36+/-4.52) cells/field] ( t=30.700, P=0.000). Under fluorescence microscopy, some of the single cell adipocytes showed a network of green fluorescence, indicating the presence of GFP labeled exogenous hADSCs in the tissue. The vascular density of new-born tissue of the transfected group [(16.37+/-2.76)/field] was significantly higher than that of the untransfected group [(9.13+/-1.68)/field] ( t=8.678, P=0.000). Conclusion: The hADSCs extracted from the lipid part after liposuction can be used as seed cells. After HGF-GFP-LVs transfection and adipose induction, the hADSCs combined with injectable fibrin glue scaffold can construct mature adipose tissue in vivo, which may stimulate angiogenesis, and improve retention rate of new-born tissue. PMID- 29798572 TI - [Construction and biocompatibility in vitro evaluation of electrospun graphene/silk fibroin nanofilms]. AB - Objective: To explore the construction and biocompatibility in vitro evaluation of the electrospun-graphene (Gr)/silk fibroin (SF) nanofilms. Methods: The electrostatic spinning solution was prepared by dissolving SF and different mass ratio (0, 5%, 10%, 15%, and 20%) of Gr in formic acid solution. The hydrophilia and hydrophobic was analyzed by testing the static contact angle of electrostatic spinning solution of different mass ratio of Gr. Gr-SF nanofilms with different mass ratio (0, 5%, 10%, 15%, and 20%, as groups A, B, C, D, and E, respectively) were constructed by electrospinning technology. The structure of nanofilms were observed by optical microscope and scanning electron microscope; electrochemical performance of nanofilms were detected by cyclic voltammetry at electrochemical workstation; the porosity of nanofilms were measured by n-hexane substitution method, and the permeability were observed; L929 cells were used to evaluate the cytotoxicity of nanofilms in vitro at 1, 4, and 7 days after culture. The primary Sprague Dawley rats' Schwann cells were co-cultured with different Gr-SF nanofilms of 5 groups for 3 days, the morphology and distribution of Schwann cells were identified by toluidine blue staining, the cell adhesion of Schwann cells were determined by cell counting kit 8 (CCK-8) method, the proliferation of Schwann cells were detected by EdU/Hoechst33342 staining. Results: The static contact angle measurement confirmed that the hydrophilia of Gr-SF electrospinning solution was decreased by increasing the mass ratio of Gr. Light microscope and scanning electron microscopy showed that Gr-SF nanofilms had nanofiber structure, Gr particles could be dispersed uniformly in the membrane, and the increasing of mass ratio of Gr could lead to the aggregation of particles. The porosity measurement showed that the Gr-SF nanofilms had high porosity (>65%). With the increasing of mass ratio of Gr, the porosity and conductivity of Gr-SF nanofilm increased gradually, the value in the group A was significantly lower than those in groups C, D, and E ( P<0.05). In vitro L929 cells cytotoxicity test showed that all the Gr-SF nanofilms had good biocompatibility. Toluidine blue staining, CCK-8 assay, and EdU/Hoechst33342 staining showed that Gr-SF nanofilms with mass ratio of Gr less than 10% could support the survival and proliferation of co cultured Schwann cells. Conclusion: The Gr-SF nanofilm with mass ratio of Gr less than 10% have proper hydrophilia, conductivity, porosity, and other physical and chemical properties, and have good biocompatibility in vitro. They can be used in tissue engineered nerve preparation. PMID- 29798573 TI - [Diagnosis and treatment strategy of tuberculosis infection after total knee arthroplasty]. AB - Objective: To review the diagnosis and treatment of tuberculosis infection after total knee arthro-plasty (TKA). Methods: The recent literature concerning the diagnosis and treatment of tuberculosis infection after TKA were extensively reviewed and summarized. Results: The diagnosis of tuberculosis infection after TKA is difficult. It should be combined with the patient's medical history, symptoms, signs, blood examinations, and imaging examinations, among which the bacterial culture and histopathological examination are the gold standard of diagnosis. Treatment strategy is combined with the drug treatment and a variety of surgical procedures that depends on the clinical situation. Conclusion: At present, there is no guideline for the diagnosis and treatment of tuberculosis infection after TKA, it still needs further study and improvement. PMID- 29798574 TI - [Clinical application progress of the Sauve-Kapandji procedure]. AB - Objective: To review the clinical application progress of the Sauve-Kapandji procedure. Methods: The indications, techniques, effectiveness, and modifications of the Sauve-Kapandji procedure were analyzed and evaluated by an extensive review of the relevant literature. Results: The Sauve-Kapandji procedure can be applied for various disorders of the distal radioulnar joint. Risk of series of complications exist, which might be reduced by modification of the procedure. Conclusion: The Sauve-Kapandji procedure, as a salvage operation, can be a good alternative by meticulous manipulation for appropriate cases with distal radioulnar joint disorders. PMID- 29798575 TI - [Application progress of digital technology in auricle reconstruction]. AB - Objective: To review the application progress of digital technology in auricle reconstruction. Methods: The recently published literature concerning the application of digital technology in auricle reconstruction was extensively consulted, the main technology and its specific application areas were reviewed. Results: Application of digital technology represented by three-dimensional (3D) data acquisition, 3D reconstruction, and 3D printing is an important developing trend of auricle reconstruction. It can precisely guide auricle reconstruction through fabricating digital ear model, auricular guide plate, and costal cartilage imaging. Conclusion: Digital technology can improve effectiveness and decrease surgical trauma in auricle reconstruction. 3D bioprinting of ear cartilage future has bright prospect and needs to be further researched. PMID- 29798576 TI - [Research progress of non-biological meshes for breast reconstruction]. AB - Objective: To review the application progress of non-biological meshes for breast reconstruction (BR). Methods: The related home and abroad researches in BR were reviewed and summarized. Results: Non-biological meshes can be divided into degradable and nondegradable. The former has many types, whether its degradation rate can match with the grow rate of repair tissue will significantly affect the wound healing and tissue intergradation. TiLOOP, on behalf of the latter, has a good postoperative performance due to its nano TiO 2 layer, lightness and flexibility. Non-biological meshes have been gradually used to cover and fix implant in BR. Compared with biological meshes, non-biological meshes are cheaper and have a more positive postoperative performance generally, but definite comparison can't be concluded due to the limited data. Conclusion: As non biological meshes are applied to BR preliminarily, their effectiveness are still needed to be observed further. PMID- 29798577 TI - [Application of plasma-mediated bipolar radiofrequency ablation debridement in treatment with retention of internal fixation for early postoperative infection of fractures of extremities]. AB - Objective: To explore the effectiveness of plasma-mediated bipolar radiofrequency ablation debridement (Coblation debridement) in treatment with retention of internal fixation for early postoperative infection of fractures of extremities. Methods: Between January 2012 and May 2015, 16 patients (12 males and 4 females) with early postoperative infection of internal fixation for extremity fracture were treated, with an average age of 41.6 years (range, 19-61 years). The fractures included tibia and fibula fracture in 5 cases, femoral fractures in 5 cases, distal humeral fractures in 3 cases, ulna and radius fractures in 2 cases, and patellar fracture in 1 case. Two cases were open fractures and 14 cases were closed fractures. All fractures were fixed non-intramedullarily. Postoperative infection occurred at 5-10 days (mean, 7 days) after operation, with bacteria cultured from wound secretion in all cases. Type EIC5872 70 Coblation knife and Coblator II plasma surgery system were conducted to debride the foci of infection in ablating pattern with sterile saline used as the conductive fluid and the magnitude of power from 6 to 9. After pulse irrigating with sterile saline, irrigating tube and draining tube were placed beside the fixation. Postoperative continuous irrigation and drainage and systemic antibiotic therapy would be conducted. The effectiveness was evaluated by bone infection effectiveness evaluation criteria. Results: All the 16 patients were followed up 12-36 months (mean, 15 months) after operation. All the infected wounds were cured and healed by first intention without recurrence in all the patients, and the fracture healing time was 3-7 months (mean, 4.8 months) without limb dysfunction or nonunion. Internal fixation was removed at 1-2 years after operation in 4 cases, whom with good fracture healing and without recurrence of infection after operation. Conclusion: The effectiveness of Coblation debridement in treatment with retention of internal fixation for early postoperative infection of extremity fractures are satisfactory, which can avoid the second stage operation, infectious nonunion, and osteomyelitis. PMID- 29798578 TI - [Short-term effectiveness of Kirschner wire elastic fixation in treatment of Doyle type I and II mallet finger]. AB - Objective: To evaluate the short-term effectiveness of Kirschner wire (K-wire) elastic fixation in the treatment of Doyle type I and II mallet finger. Methods: Between July 2016 and March 2017, 18 patients with Doyle type I and II mallet finger were treated. There were 12 males and 6 males, with an average age of 45 years (range, 16-61 years). The index finger was involved in 2 cases, the middle finger in 3 cases, the ring finger in 10 cases, and the little finger in 3 cases. The interval from injury to operation ranged from 2 hours to 45 days (median, 5.5 hours). There were 8 patients of closed wound and 10 patients of open wound. Fourteen patients were simply extensor tendon rupture and 4 were extensor tendon rupture complicated with avulsion fracture. The distal interphalangeal joints (DIPJ) of injured fingers were elastically fixed with the K-wire at mild dorsal extend position. The K-wire was removed after 6 weeks, and the functional training started. Results: The operation time was 34-53 minutes (mean, 38.9 minutes). Patients were followed up 3-8 months (mean, 5 months). All incisions healed primarily and no K-wire loosening or infection happened during the period of fixation. All mallet fingers were corrected. The range of motion (ROM) in terms of active flexion of injured DIPJ was (75.83+/-11.15) degrees at 6 weeks after operation, showing significant difference when compared with the normal DIPJ of contralateral finger [(85.28+/-6.06) degrees ] ( t=3.158, P=0.003). The ROM in terms of active flexion was (82.67+/-6.78) degrees in 15 patients who were followed up at 8 months after operation, showing no significant difference when compared with the normal DIPJ of contralateral finger [(86.00+/-5.73) degrees ] ( t=1.454, P=0.157). After the removal of K-wire at 6 weeks, visual analogue scale (VAS) score of active flexion and of passive flexion to maximum angle were 1.78+/-0.88 and 3.06+/-1.06, respectively. According to the total active motion criteria, the effectiveness was rated as excellent in 10 cases, good in 5 cases, moderate in 2 cases, and poor in 1 case, and the excellent and good rate was 83.33%. The patients' satisfaction were accessed by Likert scale, which were 3-5 (mean, 4.2). Conclusion: K-wire elastic fixation in the treatment of Doyle typeIand II mallet finger can repair the extensor effectively, correct the mallet finger deformity, and also be benefit for the flexion-extension function restoration of DIPJ. PMID- 29798579 TI - [Mid-term effectiveness of cerclage wires fixation in treatment of periprosthetic femoral fractures associated with primary hip arthroplasty]. AB - Objective: To evaluate the mid-term effectiveness of cerclage wires fixation in treating Mallory typeIIperiprosthetic femoral fractures associated with primary hip arthroplasty. Methods: A retrospective analysis was made in the data of 14 patients (14 hips) with Mallory typeII periprosthetic femoral fractures associated with primary hip arthroplasty and treated with cerclage wires fixation between January 2010 and June 2011 (fracture group). Twenty-eight patients (28 hips) without periprosthetic femoral fractures associated with primary hip arthroplasty at the same stage were chosen as control group. The uncemented femoral prosthesis were used in 2 groups. There was no significant difference in gender, age, body mass index, and primary disease between 2 groups ( P>0.05). The operation time, intraoperative blood loss, and the complications were recorded. The Harris score was used to evaluate the hip function and the visual analogue scale (VAS) score was used to evaluate the pain degree of hip. According to the postoperative X-ray films of hips, Engh et al. standard was used to evaluate the fixed and stable status of the femoral prosthesis; the heterotopic ossification was observed; the time of fracture union was recorded. Results: The operation time of fracture group was significantly longer than that of control group ( t= 3.590, P=0.001). There was no significant difference in the intraoperative blood loss between 2 groups ( t=-1.276, P=0.209). All patients were followed up 64-75 months (mean, 69.5 months). Hip dislocation after operation occurred in 1 case of fracture group; delirium symptom and nonunion of incision occurred in 1 case and 1 case of control group, respectively. There was no significant difference in the Harris score and VAS score at 6 months and 5 years between 2 groups ( P>0.05). X ray films showed that all fractures healed and the mean time of fracture union were 6.1 months (range, 3-12 months). There was no fracture nonunion or malunion evidently. There was no significant difference in X-ray score at 6 months and 5 years between 2 groups ( P>0.05). At last follow-up, cerclage wires displacement or breakage did not occur. Heterotopic ossification occurred in 2 cases of fracture group and in 1 case of control group. Conclusion: Cerclage wires fixation can achieve the good mid-term effectiveness in treating Mallory typeIIintraoprative periprosthetic femoral fractures associated with primary hip arthroplasty. PMID- 29798580 TI - [Clinical research on perioperative restrictive fluid therapy combined with preoperative urination training in total hip arthroplasty]. AB - Objective: To evaluate the effectiveness and safety of restrictive fluid therapy combined with preoperative urination training during perioperative period in an enhanced recovery after surgery (ERAS) program for primary total hip arthroplasty (THA). Methods: A retrospective study were conducted in 73 patients who underwent unilateral THA with liberal intravenous fluid therapy on the day of surgery between April 2015 and March 2016 (control group) and in 70 patients with restrictive fluid therapy and preoperative urination training between November 2016 and April 2017 (trial group). There was no significant difference in gender, age, weight, height, body mass index, primary disease, and complications between 2 groups ( P>0.05). Perioperative related indexes were recorded and compared between 2 groups, including operation time; pre-, intra-, post-operative intravenous fluid volumes, overall intravenous fluid volume on the surgery day; postoperative urine volume per hour after surgery; blood volume; total blood loss during perioperative period; usage rates of diuretics and urine tube; the incidences of hypotension, nausea and vomiting, hyponatremia, and hypokalemia after surgery; postoperative length of stay; and the expressions of inflammatory factors [C reaction protein (CRP), interleukin-6 (IL-6)] before sugery and at 1st and 2nd days after surgery. Results: The pre-, intra-, post-operative intravenous fluid volumes and the overall intravenous fluid volume on the surgery day in trial group were significantly lower than those in control group ( P<0.05). There was no significant difference in operation time, blood volume, total blood loss during perioperative period, and postoperative urine volume per hour after surgery between 2 groups ( P>0.05). The usage rates of diuretics and urine tube in trial group were significantly lower than those in control group ( P<0.05), while the differences in incidences of hypotension, nausea and vomiting, hyponatremia, and hypokalemia after surgery of 2 groups were insignificant ( P>0.05). The level of inflammation factors (CRP, IL-6) at 1st and 2nd days was significant lower in trial group than in control group ( P<0.05), with shorter postoperative length of stay ( t=-5.529, P=0.000). Conclusion: It is safe and effective to adopt restrictive fluid therapy and preoperative urination training during perioperative period (intravenous fluid volume controls in about 1 200 mL on the day of surgery) following ERAS in primary THA. However, prospective studies with large-scale are still in demand for further confirming the conclusion. PMID- 29798581 TI - [Comparison of short-term effectiveness of staged bilateral total hip arthroplasty via different approaches]. AB - Objective: To compare the short-term effectiveness of staged bilateral total hip arthroplasty via different approaches. Methods: Thirty-two patients (64 hips) with bilateral hip disease were treated with total hip arthroplasty between January 2012 and December 2014. There were 20 males and 12 females with the mean age of 45.3 years (range, 30-67 years). There were avascular necrosis of femoral head in 14 cases, developmental dislocation of the hip in 12 cases, ankylosing spondylitis in 4 cases, osteoarthritis in 2 cases. All patients were treated with total hip arthroplasty; and the direct anterior approach (DAA) or direct lateral approach (DLA) was chosen for the unilateral hip randomly. The length of incision, operation time, total blood loss volume, the time of first postoperative activity, and the acetabular anteversion angle were compared. The Harris score, visual analogue scale (VAS) score, and incidence of complication were compared between 2 groups. Results: All incisions healed at stage I. All patients were followed up 20-53 months (mean, 39.6 months). The length of incision, total blood loss volume, the time of first postoperative activity were significantly shorter in DAA group than in DLA group ( P<0.05). The operation time was significantly longer in DAA group than in DLA group ( P<0.05). There was no significant difference in acetabular anteversion angle between 2 groups ( t=1.122, P=0.266). The incidence of complication were 25.00% and 15.63% in DAA group and DLA group, respectively, showing no significant difference ( chi2=0.869, P=0.536). The Harris score in DAA group significantly increased at 3 and 9 months after operation than in DLA group ( P<0.05); there was no significant difference at 18 months after operation between 2 groups ( P>0.05). The VAS score was significantly lower in DAA group than in DLA group at 1 day, 3 days, and 1 week after operation ( P<0.05); there was no significant difference at 4 and 8 weeks between 2 groups ( P>0.05). The prosthesis did not loosen and sink during the follow-up. Conclusion: Total hip arthroplasty via DAA can reduce operation related complication and speed up the recovery of hip function at the early stage after operation. However, the lateral cutaneous nerve injury is the most common complication. PMID- 29798582 TI - [Effectiveness analysis of surgical treatment of Schatzker type IV tibial plateau fractures]. AB - Objective: To introduce a surgical protocol based on the location and orientation of the apex of the medial condylar fracture line for the treatment of Schatzker type IV tibial plateau fractures and report the preliminary effectiveness. Methods: The clinical data of 18 patients with Schatzker type IV tibial plateau fractures underwent open reduction and internal fixation between March 2012 and April 2016 were retrospectively analysed. There were 6 males and 12 females, aged 36-74 years (mean, 45 years). The causes of injury included traffic accident in 2 cases, falling in 14 cases, bruise injury in 1 case, and crush injury of heavy object in 1 case. All cases were fresh closed fractures, without injury of nerves and blood vessels. According to sub type of Wahlquist tibial plateau type IV fracture classification, there were 1 case of type A, 5 cases of type B, and 12 cases of type C. The interval of injury and operation was 6-16 days (mean, 9.5 days). The location of the apex of the medial condylar fracture line was determined the surgical approach. After operation, reduction of tibial plateau fractures was evaluated by the DeCoster score evaluation criteria. The knee joint function was assessed by short Musculoskeletal Function Assessment (SMFA) score and Hospital for Special Surgery (HSS) score. Results: The incisions all healed by first intension after operation without surgery related complications. All the patients obtained satisfactory exposure and reduction during operation. According to DeCoster score evaluation criteria, the results were excellent in 13 cases and fair in 5 cases. All the patients were followed up 12-30 months (mean, 18 months). X-ray films showed that all fractures healed at 10-16 weeks (mean, 12 weeks) after operation. There was no plate displacement, screw loosening, and other complications occurred during follow-up. At last follow-up, the SMFA score was 15-48 (mean, 28.5). The HSS score was 52-94 (mean, 81.1), and the results were excellent in 10 cases, good in 5 cases, fair in 2 cases, and poor in 1 case with an excellent and good rate of 83.3%; the main clinical manifestation was severe traumatic osteoarthritis symptom in 1 case with the fair result. Conclusion: The surgical program should be developed based on the location and orientation of the apex of the medial condylar fracture line. Open reduction and internal fixation for treating Schatzker type IV fractures can achieve satisfactory effectiveness. PMID- 29798583 TI - [Effectiveness analysis of Ilizarov external fixation and ankle arthrodesis in treatment of late traumatic ankle arthritis]. AB - Objective: To evaluate the effectiveness of Ilizarov external fixation and ankle arthrodesis in the treatment of late traumatic ankle arthritis. Methods: Between June 2013 and June 2015, 27 patients with late traumatic ankle arthritis were treated with Ilizarov external fixation technique. There were 16 males and 11 females with an age of 27-69 years (mean, 45.7 years). Sixteen cases were on the left side, 11 on the right side. All the patients suffered from traumatic ankle fractures or ligament damages caused by initial traumas. After 6 months of standard conservative treatment, the results was invalid and all patients had ankle joint pain and movement disorders. The disease duration was 3-39 years (mean, 11.5 years). According to Takakura ankle arthritis staging, there were 16 cases in stage 3 and 11 cases in stage 4. The tibial-talar angle before operation was (102.55+/-4.02) degrees measured on conventional double-feet loading anteroposterior and lateral X-ray films. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle and foot joint score was 45.72+/-6.45, and the visual analogue scale (VAS) score was 8.61+/-1.96. Results: All the patients were followed up 15-42 months (mean, 28.1 months). All ankles achieved bony fusion, the clinical healing time was 12.9 weeks on average (range, 11-18 weeks). No persistent bleeding in the incisions and needle tract occurred during the follow up. There were 4 cases of mild needle infection, 2 cases of anterior dislocation of talus, and 3 cases with different degree of limited activity. No traumatic bone defect, bone disconnection, and false joint formation was observed. At 12 months after operation, the AOFAS ankle and foot joint score, VAS score, and tibial-talar angle were 80.53+/-9.14, 2.77+/-0.82, and (94.36+/-2.48) degrees , respectively, which were significantly improved when compared with preoperative ones ( t=16.17, P=0.00; t=14.28, P=0.00; t=9.01, P=0.00). The effectivenss was excellent in 9 cases, good in 13 cases, and fair in 5 cases, with an excellent and good rate of 81.5%. Conclusion: Satisfactory effectiveness can be obtained through Ilizarov external fixation and ankle arthrodesis in the treatment of traumatic ankle arthritis, showing certain application prospect, while long-term effectiveness should be comfirmed by large sample randomized controlled trials. PMID- 29798584 TI - [Application of three-dimensional printing technology for closed reduction and percutaneous cannulated screws fixation of displaced intraarticular calcaneus fractures]. AB - Objective: To evaluate the effectiveness of three-dimensional (3-D) printing assisting minimally invasive for intraarticular calcaneal fractures with percutaneous poking reduction and cannulate screw fixation. Methods: A retrospective analysis was performed of the 19 patients (19 feet) with intraarticular calcaneal fracture who had been treated between March 2015 and May 2016. There were 13 males and 6 females with an average age of 38.2 years (range, 24-73 years). There were 3 open fractures and 16 closed fractures. By Sanders classification, 12 cases were type II, 7 cases were type III. By Essex-Lopresti classification, 13 cases were tongue type, 6 cases were joint-depression type. The time from injury to surgery was 1-10 days (mean, 4.7 days). A thin slice CT scan was taken of bilateral calcaneus in patients. By using the mirror imaging technique, the contralateral mirror image and the affected side calcaneus model were printed according to 1?1 ratio. The displacement of fracture block was observed and contrasted, and the poking reduction was simulated. Calcaneal fracture was treated by percutaneous minimally invasive poking reduction and cannulate screw fixation. The Bohler angle and Gissane angle at immediate after operation and last follow-up was measured on X-ray films, and compared with preoperative measurement. The functional recovery was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) scores. Results: The operation time was 25-70 minutes (mean, 45 minutes). The intraoperative blood loss was 10-40 mL (mean, 14.5 mL). All the incisions healed by first intention and had no relevant postoperative complications such as skin necrosis, nail tract infection, and osteomyelitis. All the patients were followed up 12-25 months (mean, 14.6 months). All patients obtained fracture healing, and the fracture healing time was 8-14 weeks (mean, 10.3 weeks). No screw withdrawal or breakage occurred during follow-up; only 1 patient with Sanders type II fracture, whose calcaneus height was partially lost at 6 weeks after operation, the other patients had no reduction loss and fracture displacement, and no traumatic arthritis occurred. The Bohler angle and Gissane angle at immediate after operation and last follow up were significantly improved when compared with preoperative ones ( P<0.05), but there was no significant difference between at immediate after operation and last follow-up ( P>0.05). The AOFAS score was 76-100 (mean, 88.2), and the results were excellent in 10 feet, good in 7, and fair in 2, the excellent and good rate was 89.5%. Conclusion: 3-D printing assisting minimally invasive for intraarticular calcaneal fractures with percutaneous poking reduction and cannulate screw fixation can reduce the surgical trauma, improve the quality of reduction and fixation, and make the operation more safe, accurate, and individualized. PMID- 29798585 TI - [Effectiveness analysis of limited small incision with simple Krackow suture in treatment of acute closed Achilles tendon rupture]. AB - Objective: To explore the effectiveness of limited small incision with simple Krackow suture in treatment of acute closed Achilles tendon rupture. Methods: Between October 2013 and July 2016, 25 cases with acute Achilles tendon rupture were repaired by simple Krackow suture via limited small incision. There were 21 males and 4 females with an average age of 33.6 years (range, 25-39 years). The left side was involved in 15 cases and the right side in 10 cases. The injury caused by sport in 22 cases and by falling in 3 cases. The time from injury to operation was 3-7 days (mean, 4.4 days). Physical examination showed that the Thompson sign and single heel raising test were positive. Results: The operation time was 30-60 minutes with an average of 39.2 minutes. All incisions healed by first intention. There was no complication of wound infection, deep vein thrombosis, tendon re-rupture, and sural nerve injury. All patients were followed up 9-20 months (mean, 14.2 months). The ankle and hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS) was 92-97 (mean, 94.9) after 9 months. The AOFAS score results were excellent in 13 cases, good in 9 cases, and fair in 3 cases. The range of motion of ankle joint was 49-58 degrees with an average of 53.7 degrees . All single heel raising tests were negative. Conclusion: The method of simple Krackow suture via limited small incision has the advantages of minimal injury, less incidence of re-rupture and sural nerve injury, quicker recovery and so on. PMID- 29798586 TI - [Effectiveness of percutaneous endoscopic spine surgery for treatment of lumbar spine disorders with intraspinal ossification]. AB - Objective: To investigate the feasibility, effectiveness, and security of percutaneous endoscopic spine surgery for treatment of lumbar spine disorders with intraspinal ossification. Methods: Between July 2008 and June 2016, 96 patients with lumbar spine disorders (lumbar disc herniation or lumbar spinal stenosis) with intraspinal ossification were treated with percutaneous endoscopic spine surgery. There were 59 males and 37 females, aged from 13 to 57 years (mean, 29.5 years). The disease duration was 3-51 months (mean, 18.2 months). Fifty-one cases had trauma history. Ninety-two cases were single segmental unilateral symptom, 4 cases were bilateral symptom. The ossification property was posterior ring apophysis separation in 89 cases, and ossification of the fibrous ring or posterior longitudinal ligament in 7 cases. There were 32 cases of lateral type, 13 cases of central type, and 51 cases of mixed type. The pressure factors, such as nucleus pulposus, hyperplasia of the yellow ligament, joint capsule, or articular osteophyma, were removed under the microscope. Local anesthesia or continuous epidural anesthesia was performed in the transforaminal approach with 50 cases, and continuous epidural anesthesia or general anesthesia was performed in the interlaminar approach with 46 cases. The visual analogue scale (VAS) score was used to evaluate the degree of leg pain preoperatively and at last follow-up. The effectiveness was evaluated at last follow-up according to the modified Macnab criteria. Results: All patients were successfully operated. Via transforaminal approach, the mean operation time was 53 minutes and the mean intraoperative fluoroscopy times was 8 times; and via interlaminar approach was 58 minutes and 3 times, respectively. The mean bed rest time after operation was 6.5 hours and the mean hospitalization time was 4.7 days. All patients were followed up 6-18 months (median, 11 months). Postoperative lumbar CT scan and three-dimensional reconstruction after 3 days of operation showed that ossification tissues of 26 cases were not resected, 12 cases were resected partly, and 49 cases were resected completely. Postoperative lumbar MRI after 3 months of operation showed that spinal cord and nerve root were not compressed. At last follow-up, VAS score of leg pain was 0.7+/-1.1, which was significantly lower than preoperative score (5.8+/-1.1) ( t=1.987, P=0.025). At last follow-up, according to modified Macnab criteria, the results were excellent in 87 cases, good in 5 cases, and fair in 4 cases, and the excellent and good rate was 95.8%. Conclusion: Percutaneous endoscopic spine surgery for treatment of lumbar spine disorders with intraspinal ossification is an effective, safe, and minimal invasive alternative, and the short-term effectiveness is reliable. Accounting for the treatment of intraspinal ossification, comprehensive analysis should be made by combining clinical symptoms, imaging characteristics, and risk assessment. PMID- 29798587 TI - [Short-term effectiveness of accurate decompression via foraminoplasty in treatment of lumbar lateral recess stenosis]. AB - Objective: To discuss the effectiveness and the safety of accurate decompression via foraminoplasty in treating lumbar lateral recess stenosis patients who accompanied by disk-flavum ligamentum space and bony lateral recess stenosis, and to analysis the short-term effectiveness of the surgical procedures. Methods: Forty-five lumbar lateral recess stenosis patients accompanied by disk-flavum ligamentum space and bony lateral recess stenosis were treated by accurate decompression via foraminoplasty between January 2013 and January 2016. There were 29 males and 16 females with a median age of 58 years (range, 42-82 years). The disease duration was 3-96 months (mean, 24.4 months). The lesion segment included L 4, 5 in 36 cases and L 5, S 1 in 9 cases. The visual analogue scale (VAS) score of low back pain and leg pain at preoperation and last follow-up were recorded, and the modified Macnab criteria was used to evaluate the effectiveness at last follow-up. Postoperative CT and MRI were reviewed to evaluate the stability and decompression of the lumbar spine. Results: All operations were successfully completed. All the 45 patients were followed up 3-18 months (median, 11 months). Dural tear occurred in 2 cases during operation, bone graft removed into the spinal canal in 1 case, postoperative low back pain occurred in 5 cases, and there was no nerve root injury, hematoma formation, or other complications. The leg pain VAS score at last follow-up (0.6+/-1.2) was significantly improved when compared with preoperative score (5.7+/-1.4) ( t=8.981, P=0.001); and the low back pain VAS scores showed no significant difference between preoperation and last follow-up (1.5+/-1.3 vs. 1.7+/-1.4; t=0.535, P=0.585). According to the modified Macnab criteria, the results were excellent in 20 cases, good in 22 cases, fair in 2 cases, and poor in 1 case at last follow-up, and the excellent and good rate was 93.3%. Conclusion: Accurate decompression via foraminoplasty is an effective, safe, and less invasive way for treating lumbar recess stenosis patients accompanied by disk-flavum ligamentum space and bony lateral recess stenosis. PMID- 29798588 TI - [Comparison of effectiveness of cortical bone trajectory screw fixation and pedicle screw fixation in posterior lumbar interbody fusion]. AB - Objective: To compare the effectiveness of cortical bone trajectory screw (CBTS) and conventional pedicle screw for posterior lumbar interbody fusion (PLIF) in the treatment of single segment lumbar degenerative disease. Methods: Between May 2013 and May 2016, a total of 97 patients with single segment lumbar degenerative disease were treated with PLIF. Fifty-one patients were fixed with CBTS in PLIF (trajectory screw group) and 46 with pedicle screw (pedicle screw group). There was no significant difference in age, gender, body mass index, preoperative diagnosis, lesion segment, and preoperative visual analogue scale (VAS) score, Oswestry dysfunction index (ODI) between 2 groups ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage, bed rest time, length of hospital stay, serum creatine kinase (CK) concentration, total amount of diclofenac sodium, perioperative complications, ODI, VAS score, and interbody fusion rate were recorded and compared between 2 groups. Results: All patients were followed up 12 months. The patients in trajectory screw group had a significantly less operation time, intraoperative blood loss, postoperative drainage, and serum CK concentration when compared with the patients in pedicle screw group ( P<0.05). Thirty-five patients (68.6%) in trajectory screw group and 46 patients (100%) in pedicle screw group were given diclofenac sodium within 48 hours after operation, showing significant difference between 2 groups ( chi2=89.334, P=0.000). There was no significant difference in the incidence of perioperative complications between trajectory screw group and pedicle screw group (3.9% vs. 8.7%, P=0.418). There was no significant difference in the VAS score, ODI, and interbody fusion rate at 12 months after operation between 2 groups ( P>0.05). Conclusion: For the single segment degenerative lumbar disease, the use of CBTS or conventional pedicle screw for PLIF can obtain satisfactory clinical function and interbody fusion rate. But the former has the advantages of less blood loss, less intraoperative muscle damage, less perioperative pain, shorter length of hospital stay and bed rest time. PMID- 29798589 TI - [An anatomical study of lumbar unilateral transverse process-pedicle percutaneous vertebral augmentation]. AB - Objective: To measure the anatomical parameters related to lumbar unilateral transverse process-pedicle percutaneous vertebral augmentation, and to assess the feasibility and safety of the approach. Methods: A total of 300 lumbar vertebral bodies of 60 patients were randomly selected, and vertebral augmentation were simulated 600 times on X-ray and CT image with unilateral conventional transpedicle approach (control group) and unilateral transverse process-pedicle approach (experimental group). The distance between the entry point and the midline of the vertebral body, the puncture inner inclination angle, the safe range of the puncture inner inclination angle, and the puncture success rate were measured and compared between the left and right with the same approach, and between the two approaches. Results: The distance between the entry point and the midline gradually increased from L 1 to L 5 on both sides in the 2 groups. In the control group, the right sides distance of L 1 and L 2 was much longer than the left sides, and the right sides distance of L 1, L 2, and L 5 was much longer than the left sides in the experimental group ( P<0.05); the distance of the experimental group between the entry point and the midline was much longer than the control group regardless of the sides from L 1 to L 5 ( P<0.05). In the experimental group, the right maximum inner inclination angle from L 1 to L 5, the right middle inner inclination angle from L 1 to L 5, and the right minimum inner inclination angle from L 1, L 2, L 4, L 5 were significantly larger than the left side ( P<0.05). The maximum inner inclination angle and the middle inner inclination angle presented increased tendency, the tendency of minimum inner inclination angle was ambiguous, however, the all inner inclination angles were much larger than those in control group among the different lumbar levels( P<0.05). There was no significant difference of the safe range of the puncture inner inclination angle between 2 sides in 2 groups at L 1 to L 5 ( P<0.05); the safe range angle in experimental group at L 5 was significantly smaller than that in control group ( P<0.05). The difference in total puncture success rate of all lumbar levels was significant between the experimental group and the control group ( chi2=172.252, P=0.000); the puncture success rates of the experimental group were higher than those in the control group form L 1 to L 4 ( P<0.05), but no significant difference was found in the puncture success rate between 2 groups at L 5 ( P>0.05). Conclusion: Compared with the unilateral conventional transpedicle approach, the entry point of the unilateral transverse process pedicle approach is localized outside, the puncture inclination angle is wider, and the puncture success rate is higher. It shows that the unilateral transverse process-pedicle approach is safer and more reliable than the unilateral conventional transpedicle approach. PMID- 29798590 TI - [Correlation study between sagittal lumbar facet joint and degenerative lumbar spondylolisthesis]. AB - Objective: To study the relationship between sagittal facet joint and degenerative lumber spondylolisthesis (DLS) by observing the changes of the lumbar facet joint angle. Methods: Fifty-seven patients with DLS who met the inclusion criteria between January 2013 and February 2016 were collected (DLS group). There were 26 males and 31 females, with the mean age of 54.0 years (range, 34-84 years). Forty patients without DLS at same stage were collected as control group. There were 23 males and 17 females with the mean age of 55.6 years (range, 29-82 years). There was no significant difference in gender and age between 2 groups ( P>0.05). The lumbar facet joint angles were measured and compared by MRI scanning images in 2 groups. In DLS group, X-ray films were used to evaluated the degree of the lumbar spondylolisthesis on the basis of the Meyerding standard, and compared the facet joint angles between patients of different DLS degree. Results: Facet joint angles in the DLS group [(34.18+/- 4.81) degrees ] were significantly smaller than those in control group [(45.87+/ 1.09) degrees ] ( t=15.073, P=0.000). In DLS group, the patients were rated as degree I in 24 cases, degree II in 19 cases, degree III in 14 cases. As the degree of DLS increased, the lumbar joint angle decreased gradually, and showing significantly differences between patients of different DLS degree ( P<0.05). Conclusion: Sagittal lumbar facet joint may be one of the main risk factors of DLS. PMID- 29798591 TI - [Clinical research of sideburn reconstruction with expanded island scalp flap based on parietal branch of superficial temporal vessel]. AB - Objective: To explore the feasibility and effectiveness of sideburn reconstruction using the expanded island scalp flap based on the parietal branch of the superficial temporal vessel. Methods: Between February 2012 and April 2015, 7 patients underwent sideburn reconstruction. There were 3 males and 4 females with an average age of 15 years (range, 4-44 years). The etiologies included burn injury in 3 cases, trauma in 1 case, radiation therapy in 1 case, and congenital melanocytic nevus in 2 cases. The size of the sideburn defects ranged from 5.0 cm*3.5 cm to 16.0 cm*10.0 cm. At the first-stage, according to the sideburn defect, a tissue expander of the appropriate size was inserted beneath the superficial temporal fascia which containing the parietal branch of the superficial temporal vessel. Postoperatively, regular saline injection was commenced. After 3-6 months of the first-stage surgery, the expander was adequately inflated. While the second-stage surgery was performed, the lesion was excised and the tissue expander removed. The expanded island scalp flap based on the parietal branch of the superficial temporal vessel was harvested and advanced towards the defect of the sideburn according to the contralateral normal one, and the size of flap ranged from 8 cm*3 cm to 17 cm*11 cm. The donor site was closed primarily. Results: All flaps survived and the wound and donor sites were healed primarily without any complication. All patients were followed up 1-36 months (mean, 9.8 months). The profile, hair density, and hair direction of the new sideburn were similar to the contralateral sideburn. In 1 patient, the reconstructed sideburn was a little larger than the contralateral normal one. After laser hair removal, the patient was satisfied with the appearance. Conclusion: The expanded island scalp flap based on the parietal branch of the superficial temporal vessel provides an effective option for the sideburn reconstruction, which presents with the similar appearance to the contralateral one. PMID- 29798592 TI - [Reconstruction of the donor area of distally based sural flap with relaying lateral gastrocnemius artery perforator propeller flap]. AB - Objective: To investigate the clinical application of relaying lateral gastrocnemius artery perforator flap in reconstruction of the donor defect after distally sural flap transferring. Methods: Between January 2014 and January 2016, 12 cases with foot and ankle defects were treated. There were 10 males and 2 females with an average age of 23.4 years (mean, 14-52 years). The injury was caused by motorcycle accident in 7 cases and traffic accident in 5 cases. The injury located at left limb in 7 cases and right limb in 5 cases. The size of soft tissue ranged from 10 cm*4 cm to 12 cm*6 cm. The disease duration was 2-84 hours (mean, 26.2 hours). The foot and ankle defects were reconstructed by distally sural flaps, then the flap donor sites were reconstructed with relaying lateral gastrocnemius artery perforator flap at the same stage. The size of distally sural flap ranged from 11 cm*5 cm to 13 cm*7 cm. The size of relaying flap ranged from 7 cm*4 cm to 10 cm*6 cm. Results: All flaps survived uneventfully. All recipient sites and donor sites healed smoothly. No vascular crisis, wound dehiscence, or evident swelling occurred. All patients were followed up 6-14 months (mean, 12.4 months) with satisfied esthetic and functional results in recipient and donor sites. There were only linear scar on the donor sites. The color and contour was satisfying, the function of calf and foot were not affected. Conclusion: The relaying lateral gastrocnemius artery perforator flap combined with distally sural flap is an idea choice to reconstruct foot and ankle defect, which can avoid donor site skin grafting, minimize donor site morbidity. PMID- 29798593 TI - [Anatomical study on the repair of femoral nerve injury with anterior branch of obturator nerve]. AB - Objective: To investigate the feasibility of the anastomosis of the anterior branch of obturator nerve and the muscular branch of femoral nerve. Methods: Five fresh frozen cadavers, including 3 males and 2 females, were included. Both of the obturator nerve, femoral nerve and their branches were dissected, then their routes and anatomical positions were observed. The diameter and the number of myelinated nerve fiber of the anterior branch of obturator nerve and femoral nerve muscular branches were measured, as well as the overlap distance between them. Results: The diameter of myelinated nerve fiber of the anterior branch of obturator nerve was (3.80+/-1.22) mm; the number of myelinated nerve fiber was 11 358+/-800. The diameters of the rectus femoris branch and the medial femoral branch were (1.60+/-0.54) mm and (2.20+/-0.66) mm, respectively; the number of myelinated nerve fiber were 4 961+/-655 and 6 666+/-466. Both the diameter and number of myelinated nerve fiber were close to the anterior branch of obturator nerve. The anterior branch of obturator nerve could be directly anastomosed with each nerve branch of femoral nerve in nontension, and the overlap distance was about 30 mm. Conclusion: It is feasible to repair the femoral nerve by transposed the anterior branch of obturator nerve and anastomosed with the femoral nerve muscular branches. And the rectus femoris branch and the medial femoral branch should be taken as the recipient nerve. PMID- 29798594 TI - [Effect of ursolic acid on proliferation and apoptosis of human osteosarcoma cell line U2-OS]. AB - Objective: To investigate the effect of ursolic acid on the proliferation and apoptosis of human osteosarcoma cell line U2-OS and analyze its mechanism. Methods: Human osteosarcoma cell line U2-OS was divided into 4 groups, which was cultured with ursolic acid of 0, 10, 20, and 40 MUmol/L, respectively. At 0, 24, 48, and 72 hours after being cultured, the cell proliferation ability was detected by cell counting kit 8 (CCK-8). At 48 hours, the effects of ursolic acid on cell cycle and apoptosis of U2-OS cells were measured by flow cytometry. Besides, the expressions of cyclin D1 and Caspase-3 were detected by real-time fluorescent quantitative PCR and Western blot. Results: CCK-8 tests showed that the absorbance ( A) value of each group was not significant at 0 and 24 hours ( P>0.05); but the differences between groups were significant at 48 and 72 hours ( P<0.05). Flow cytometry results showed that, with the ursolic acid concentration increasing, the G 1 phase of U2-OS cells increased, the S phase and G 2/M phase decreased, and cell apoptosis rate increased gradually. There were significant differences between groups ( P<0.05). Compared with the 0 MUmol/L group, the relative expressions of cyclin D1 mRNA and protein in 10, 20, and 40 MUmol/L groups significantly decreased ( P<0.05); whereas, there was no significant difference in relative expression of Caspase-3 mRNA between groups ( P>0.05). However, with the ursolic acid concentration increasing, the relative expressions of pro-Caspase-3 protein decreased and the relative expressions of activated Caspase-3 increased; there were significant differences between groups ( P<0.05). Conclusion: Ursolic acid can effectively inhibit the proliferation of osteosarcoma cell line U2-OS, induce the down-regulation of cyclin D1 expression leading to G 0/G 1 phase arrest, increase the activation of Caspase-3 and promote cell apoptosis. PMID- 29798595 TI - [Effects of human urine-derived stem cells combined with chondroitinase ABC on the expressions of nerve growth factor and brain-derived neurotrophic factor in the spinal cord injury]. AB - Objective: To explore the effects of human urine-derived stem cells (hUSCs) and hUSCs combined with chondroitinase ABC (chABC) on the expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spinal cord injury (SCI) of rats, and to investigate the underlying mechanism. Methods: hUSCs were cultured from human urine, and their phenotypes were detected by flow cytometry. The SCI model of rats were made via Allen method. Sixty Sprague Dawley rats were divided into 5 groups ( n=12): the sham operation group (group A), SCI group (group B), SCI+hUSCs group (group C), SCI+chABC group (group D), and SCI+hUSCs+chABC group (group E). Basso, Beattie, Bresnahan (BBB) score was used to measure the lower extremity motor function of rats in each group at 10, 20, and 30 days after operation. Real-time fluorescent quantitative PCR was used to detect the relative mRNA expressions of NGF and BDNF at 30 days. Meanwhile, the protein expression of NGF and BDNF were confirmed by immunohistochemistry staining. The relative protein expressions of Bax and Bcl-2 were detected by Western blot. Results: The hUSCs were identified to have multipotential differentiation potential. At 10, 20, and 30 days, BBB score was significantly lower in group B than in groups A, C, D, and E, in groups C, D, and E than in group A, in groups C and D than in group E ( P<0.05). Real-time fluorescent quantitative PCR and immunohistochemistry staining demonstrated that the expressions of NGF and BDNF were significantly lower in group B than in groups A, C, D, and E, in groups C, D, and E than in group A, in groups C and D than in group E ( P<0.05); but there was no significant difference between groups C and D ( P>0.05). Western blot results indicated that the protein expression of Bax was significantly higher in group B than in groups A, C, D, and E, in groups C, D, and E than in group A, in groups C and D than in group E ( P<0.05). Meanwhile, the protein expression of Bcl-2 was significantly lower in group B than in groups A, C, D, and E, in groups C, D, and E than in group A, in groups C and D than in group E ( P<0.05). Conclusion: hUSCs can protect SCI and this positive effect can be enhanced by chABC; this neuro-protective effect may depend on promoting the expressions of NGF and BDNF, and suppressing the neuronal apoptosis. PMID- 29798596 TI - [Radiological evaluation of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan composite microspheres combined with coral hydroxyapatite artificial bone in repairing large segmental bone defects]. AB - Objective: To evaluate the osteogenic effect of dextran sulfate/recombinant human bone morphogenetic protein 2/chitosan (DS/rhBMP-2/CS) combined with coralline hydroxyapatite (CHA) in repairing large segmental bone defects by radiographic feature. Methods: Fifty-seven 24-week-old male New Zealand rabbits were prepared for establishing right radius bone defect model of 20 mm in length. In which 54 rabbits were randomly divided into 3 groups ( n=18), and the CHA, DS/rhBMP 2/CS/CHA, and rhBMP-2/CHA artificial bone grafts were implanted into the bone defect in groups A, B, and C respectively; the remaining 3 rabbits were implanted nothing as blank control group. After operation, the gross condition of the animals was observed; at 4, 8, and 12 weeks after operation, X-ray film observation, Micro-CT scanning, and three-dimensional reconstruction were performed to obtain the volume of the new bone. Results: The experimental animals recovered well and were in normal condition. X-ray observation showed that the bone healing in group B was better than that in groups A and C at each time point. At each time point after operation, the X-ray scores of group B were significantly higher than that of group A and group C ( P<0.05); the scores of group C at 8 and 12 weeks after operation were significantly higher than that of group B ( P<0.05). Micro-CT scanning and three-dimensional reconstruction observation showed that at each time point after operation in group A, the bone defect area had less bone formation and poor osteogenesis; in group B, there were many new bone tissues in bone defect area, and the bone remodeling was well, and gradually closed to normal bone morphology at 12 weeks; in group C, there were many new bone tissues in bone defect area, but the bone formation was general. The new bone volume of group B was significantly higher than that of group A and group C ( P<0.05) at each time point after operation, and the score of group C was higher than that of group A at 8 weeks after operation ( P<0.05). Conclusion: The osteogenic effect of DS/rhBMP-2/CS/CHA sustained-release artificial bone is much better than that of single CHA and rhBMP-2/CHA, which can provide a new idea for treating bone defect by using bone tissue engineering in the future. PMID- 29798597 TI - [Research progress of the donor factors and experimental factors affecting adipogenic differentiation of adipose derived stem cells]. AB - Objective: To summarize the donor factors and experimental factors that affect adipogenic differentiation of adipose derived stem cells, so as to provide reference for adipogenic differentiation of adipose derived stem cells. Methods: The related research literature about donor factors and experimental factors affecting adipogenic differentiation of adipose derived stem cells in recent years was extensively reviewed and summarized. Results: There are a lot of donor factors and experimental factors affecting adipogenic differentiation of adipose derived stem cells, but some of the factors are still controversial, such as donor age, health status, adipose tissue of different parts, and so on. These factors need to be further studied. Conclusion: The donor factors and experimental factors that affect adipogenic differentiation of adipose derived stem cells should be deeply studied and the controversial issues should be clarified to lay a solid foundation for the application of adipose derived stem cells in adipose tissue engineering. PMID- 29798598 TI - [Research progress of drug-loaded antibacterial coating of orthopedic metal implants]. AB - Objective: To investigate the research progress of drug-loaded antibacterial coating of orthopedic metal implants in recent years. Methods: The recent literature on the drug-loaded antibacterial coating of orthopedic metal implants were reviewed. The research status, classification, and development trend of drug loaded antibacterial coating were summarized. Results: The drug-loaded antibacterial coating of orthopedic metal implants can be divided into passive release type and active release type according to the mode of drug release. Passive drug release coating can release the drug continuously regardless of whether the presence of bacteria around the implants. Active drug release coating do not release the drug unless the presence of bacteria around the implants. Conclusion: The sustained and stable release of drugs is a key problem to be solved in various antibacterial coatings research. The intelligent antibacterial coating which release antibiotics only in the presence of bacteria is the future direction of development. PMID- 29798599 TI - [Research progress of growth factor sustained-release microspheres in fat transplantation]. AB - Objective: To review the research progress of growth factor sustained-release microspheres in fat transplantation. Methods: The recently published 1iterature at home and abroad related the growth factor sustained-release microspheres in fat transplantation was reviewed and analyzed. Results: The sustained-release microsphere carrier materials include natural polymer materials and synthetic polymer materials.The sustained-release complexes of different microsphere materials with different growth factors can promote the vascularization of transplanted fat in a timely manner, improve the survival rate of grafts, and reduce the incidence of complications such as liquefaction, calcification, and necrosis. Conclusion: The growth factor sustained-release microspheres have the characteristics of persistence and controllability, which is a research hotspot in the field of fat transplantation and has broad application prospects. PMID- 29798600 TI - [Preliminary application of three dimensional printing personalized navigation template in assisting total elbow replacement for patients with elbow tumor]. AB - Objective: To explore the clinical methods of resection of elbow tumor and total elbow replacement with custom personalized prosthesis based on three dimensional (3-D) printing navigation template. Methods: In August 2016, a 63-year-old male patient with left elbow joint tumor was treated, with the discovery of the left distal humerus huge mass over 3 months, with elbow pain, activity limitation of admission. Computer-assisted reduction technique combined with 3-D printing was used to simulate preoperative tumor resection, a customized personal prosthesis was developed; tumor was accurately excised during operation, and the clinical result was evaluated after operation. Results: The time was 46 minutes for tumor resection, and was 95 minutes for personalized implant and allograft bone without fluoroscopy. X-ray and CT examination at 1 week after operation showed good position of artificial elbow joint; the anteversion of ulna prosthesis was 30 degrees and the elbow carrying angle was 15 degrees , which were consistent with the simulated results before surgery. The finger flexion was normal at 1 month after operation; the range of motion was 0-130 degrees for elbow flexion and extension, 80 degrees for forearm pronation, and 80 degrees for forearm supination. The elbow function was able to meet the needs of daily life at 7 months after operation, and no recurrence and metastasis of tumor were observed. Conclusion: For limb salvage of elbow joint, computer aided design can make preoperative surgical simulation; the navigation template can improve surgical precision; and the function of elbow joint can be reconstructed with customized and personlized prosthesis for total elbow replacement. PMID- 29798601 TI - [Development and clinical application of a new type of intramedullary nail tail cap]. AB - Objective: To develop a new type of tail cap for closing the tail of the central hole of the interlocking intramedullary nail so as to reduce difficulty in implantation of the tail cap into intramedullary nail, and ensure the accuracy of implantation, as well as reduce unnecessary operation time. Methods: In 2014, the new type of intramedullary nail tail cap ("new tail cap" for short) was successfully developed, and has been granted national utility model patent. A randomized controlled clinical trial was conducted in 34 patients with non pathological femoral shaft fractures treated between August 2014 and March 2016. The patients were randomly divided into groups A and B, 17 patients each group. There was no significant difference in gender, age, side, body mass index, cause of injury, injury to operation time, and fracture AO classification between groups ( P>0.05), with comparability. All patients underwent fixation with interlocking intramedullary nail, and the new tail cap and original tail cap were used in groups A and B respectively. The blood loss and operation time during tail cap implantation, fracture healing time, and complications were recorded and compared between 2 groups; the limb function was evaluated by Klemm function evaluation standard. Results: The blood loss and operation time during tail cap implantation of group A [(3.5+/-0.8) mL and (10.57+/-3.15) s] were significantly less than those of group B [(5.5+/-1.7) mL and (21.99+/-6.90) s] ( t=-8.281, P=0.010; t=-10.743, P=0.009). All new tail caps were successfully implanted by one-time in group A, and the one-time success rate was 100%; the original tail cap exfoliation occurred in 3 cases of group B, and the one-time success rate was 82.4%. All the patients were followed up 6-16 months (mean, 9.7 months); there was no deep infection, loosening or breakage of internal fixation, and other serious complications. The time of fracture healing was (16.4+/-3.2) weeks in group A and (15.8+/-3.5) weeks in group B, showing no significant difference ( t=0.514, P=0.611). At last follow-up, according to the Klemm function evaluation standard, the results were excellent in 14 cases and good in 3 cases in group A, and were excellent in 11 cases and good in 6 cases in group B, showing no significant difference between 2 groups ( chi2=0.142, P=0.707). Conclusion: The new type of femoral intramedullary nail tail cap can simplify operation, shorten operation time, and reduce blood loss, and it has satisfactory effectiveness. PMID- 29798602 TI - [Comparison of early effectiveness between different approaches in primary total hip arthroplasty]. AB - Objective: To compare the early effectiveness between by anterior approach via Bikini incision and by OCM approach in the primary total hip arthroplasty (THA). Methods: Between June 2015 and March 2016, 60 patients with ischemic necrosis of the femoral head who accorded with the inclusion criteria were chosen in the study, who were divided into 2 groups according to different surgical approaches. THA was performed on 30 patients by anterior approach via Bikini incision (group A), and on 30 patients by OCM approach (group B). There was no significant difference in age, gender, body mass index, side of affected hip, Steinberg stage of ischemic necrosis of femoral head, preoperative hemoglobin, preoperative Harris score, and preoperative visual analogue scale (VAS) between 2 groups ( P>0.05). The operation time, length of incision, intraoperative blood loss, transfusion rate, starting time of straight leg raising exercise, starting time of active abduction of hip, hospitalization time, the incidence of limb length discrepancy, postoperative Harris score and VAS score were recorded and compared between 2 groups. Anteroposterior pelvic X-ray films were taken to measure acetabular abduction and acetabular anteversion. Results: Primary healing of incision was obtained in all patients of 2 groups, and there was no significant difference in complication between 2 groups ( chi2=0.144, P=0.704). All the patients of 2 groups were followed up 3 to 12 months, averaged 6 months. There was no significant difference in operation time, length of incision, intraoperative blood loss, transfusion rate, hospitalization time, and starting time of straight leg raising exercise between 2 groups ( P>0.05). Group A was significantly shorter than group B in starting time of active abduction of hip ( t=-4.591, P=0.000), and was significantly lower than group B in the incidence of limb length discrepancy ( chi2=5.455, P=0.020). After operation, neither Harris score at 2 weeks, 6 weeks, 3 months, and 6 months nor VSA score at 24 hours and 6 weeks showed significant difference between 2 groups ( P>0.05). The anteroposterior pelvic X-ray films showed that all the prostheses were in good position, and there was no femoral prosthesis subsidence, acetabular cup displacement or dislocation. No significant difference was found in acetabular abduction and acetabular anteversion at 2 days after operation between 2 groups ( t=0.887, P=0.379; t=0.652, P=0.517). Conclusion: Both of two approaches in THA can avoid muscle damage and achieve favorable short-term effectiveness. But, anterior approach via Bikini incision is superior to OCM approach in starting time of active abduction of hip and the incidence of limb length discrepancy. PMID- 29798603 TI - [Detection and influence factor of serum metal ions concentration level after resurfacing arthroplasty of the hip]. AB - Objective: To observe the tendency of serum cobalt (Co), chromium (Cr), and molybdenum (Mo) ions concentration level after resurfacing arthroplasty of the hip (RSAH) by inductively coupled plasma mass spectrometer (ICP-MS), and analyze the influence factors. Methods: Forty-seven patients (55 hips) underwent RSAH between June 2005 and November 2014 who had good joint function (Harris score were >85) at every review time were selected in the study. There were 25 males and 22 females, with the mean age of 49.7 years (range, 18-64 years). The disease causes included developmental dysplasia of the hip (DDH) in 18 cases (22 hips) and non-DDH in 29 cases (33 hips). The follow-up time was 6 months to 5 years (mean, 3.2 years). The concentrations of Co, Cr, and Mo ions were measured by ICP MS, and were compared with those of 6 normal controls. Based on the analysis of the measured results, patients were chosen and grouped according to prosthesis position and femoral head prosthesis diameter. A correlative analysis was made between serum metal ions concentration and various factors (age, body mass index, pre- and post-operative Harris scores, neck-shaft angle, and stem-shaft angle). Results: The concentration of serum Co ion reached the peak at 1 year after operation ( P<0.05), and then slowly decreased, increased again at 4 years after operation and was close to the 2nd-year level at 5 years. The concentration of serum Cr ion reached its peak at 9 months after operation ( P<0.05), and then gradually decreased, and was close to normal level at 5 years. The concentration of serum Mo ion kept increase trend and reached the peak at 5 years ( P<0.05). Thirty-five hips of 29 patients followed up 9 months and 1 year were grouped. For DDH and non-DDH patients, Co and Cr ion concentrations of 40-45 degrees abduction angle of acetabular component were significantly lower than those of <40 degrees and >45 degrees ( P<0.05), but there was no significant difference in Mo ion concentration ( P>0.05). For all patients, Co, Cr, and Mo ion concentrations of 15-20 degrees anteversion angle of acetabular component were significantly lower than those of <15 degrees and >20 degrees ( P<0.05). Co, Cr, and Mo ion concentrations of >=48 mm diameter of the femoral component were significantly lower than those of <48 mm ( P<0.05). There was a negative correlation between Co ion and postoperative Harris score ( r=-0.486, P=0.041). Conclusion: The serum Co and Cr ions concentrations increase obviously at 1 year and 9 months after RSAH operation, and Mo ion concentration displays an increase trend. The metal ions concentrations have close relationship with the position of acetabular component. PMID- 29798604 TI - [Clinical evaluations of anterior cruciate ligament reconstruction with platelet rich plasma]. AB - Objective: To investigate the clinical outcomes of autologous platelet rich plasma (PRP) for anterior cruciate ligament (ACL) reconstruction. Methods: Between August 2014 and August 2016, 42 patients with ACL ruptures who underwent arthroscopic ACL reconstruction were randomly divided into 2 groups: 21 patients received graft soaked with PRP (trial group) and 21 patients received routine graft in ACL reconstruction (control group). Because 6 patients failed to be followed up, 17 patients of trial group and 19 of control group were enrolled in the study. There was no significant difference in gender, age, body mass index, side, injury reason, disease duration, Kellgren-Lawrence grade, and preoperative visual analogue scale (VAS), Lysholm score, and International Knee Documentation Committee (IKDC) activity scores between 2 groups ( P>0.05). VAS score, Lysholm score, and IKDC activity scores were used to evaluate pain and function at 3 and 12 months postoperatively. Further, second arthroscopy and MRI examination were performed at 12 months postoperatively. Results: The patients in both groups were followed up 3 to 12 months with an average of 9.83 months. The VAS score, Lysholm score, and IKDC activity scores were significantly improved at 3 and 12 months after operation in 2 groups ( P<0.05), and the scores of trial group were significantly better than those of control group at 3 months ( P<0.05), but no significant difference was found between 2 groups at 12 months ( P>0.05). No complications of effusion, infection, and allergy were observed in 2 groups during follow-up. MRI showed good position of ACL grafts and good signal quality of the graft in the majority of the cases. However, mixed hyperintense and presence of synovial fluid at the femoral bone-tendon graft interface were found in 3 patients of trial group and 4 patients of control group, indicating poor remodeling ligamentation. MRI score was 3.53+/-1.13 in trial group and was 3.21+/ 0.92 in control group, showing no significant difference ( t=0.936, P=0.356). The second arthroscopy examination showed ligament remodeling score was higher in trial group than control group ( t=3.248, P=0.014), but no significant difference was found in synovial coverage score and the incidence of cartilage repair ( t=2.190, P=0.064; chi2=0.090, P=0.764). Conclusion: PRP application in allograft ACL reconstruction can improve knee function and relieve pain after operation, which may also accelerate graft remodeling. PMID- 29798605 TI - [Effect on time of temporarily-closed wound drainage on blood loss of primary total knee arthroplasty after intravenous and intra-articular injection of tranexamic acid]. AB - Objective: To investigate the effect and safety of time of temporarily-closed wound drainage on blood loss of primary total knee arthroplasty (TKA) after intravenous and intra-articular injection of tranexamic acid (TXA). Methods: Eighty female patients were selected from 102 patients who underwent primary TKA between September 2015 and July 2016, who were randomly divided into 4 groups: control group (group A), 30 minutes group (group B), 60 minutes group (group C), and 90 minutes group (group D), 20 patients each group. No significant difference was found in age, body mass index, side, pathogen, duration, and preoperative hemoglobin, albumin, and hematocrit between 4 groups ( P>0.05). All the patients received intravenous injection of 1 g TXA at 10 minutes before removing the tourniquet. The patients in group A were injected with 60 mL normal saline into the articular cavity and closed drainage after surgery, while the patients in groups B, C, and D were injected with 60 mL TXA into the articular cavity and closed drainage for 30, 60, and 90 minutes respectively. The volume of drainage at 24 hours after operation, the total blood loss, the postoperative hemoglobin level, maximum hemoglobin loss, albumin loss, the volume and frequency of blood transfusion, venous thrombo embolism rate, and pulmonary embolism rate were recorded and compared between groups. Results: The volume of drainage and total blood loss in groups B, C, and D were less than those of group A, showing significant difference between groups C, D and group A ( P<0.05), but no significant difference between group B and group A ( P>0.05). The volume of drainage at 24 hours after operation in group B was higher than that in groups C and D, showing significant difference between groups B and D ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). There was no significant difference in the total blood loss between groups B, C, and D ( P>0.05). The hemoglobin loss and albumin loss gradually decreased from groups A to D, but no significant difference was found between groups ( P>0.05). No venous thrombo embolism and pulmonary embolism occurred. The hemoglobin value decreased to 28 g/L at 3 days after operation in 1 patient of group D, who received venous transfusion of 20 g human albumin. Conclusion: Intravenous and topical application of TXA in TKA can significantly decrease postoperative bleeding. Topical TXA combined with 60 minutes temporarily-closed wound drainage may reduce postoperative blood loss to the greatest extent without increasing the risk of venous thrombo and pulmonary embolism event after TKA.. PMID- 29798606 TI - [Change of inflammatory cytokines levels in both synovial fluid and plasm of patients with primary knee medical osteoarthritis after high tibial osteotomy]. AB - Objective: To investigate interleukin-1beta (IL-1beta), IL-6, and IL-17 levels in both synovial fluid and serum of patients with primary knee medial osteoarthritis (OA) after high tbial osteotomy (HTO). Methods: Twenty-six patients with primary knee medial OA undergoing HTO between January 2011 and June 2014 (experimental group) and 30 healthy individuals (control group) were recruited into the study. There was no significant difference in gender, age, and body mass index between 2 groups ( P>0.05). The X-ray film was taken to record healing time at osteotomy site, to measure the tibiofemoral angle, and to assess limb alignment after HTO. Visual analogue scale (VAS) pain score and knee society score (KSS) were used to evaluate pain level and function of the knee. The IL-1beta, IL-6, and IL-17 concentrations in both plasma and synovial fluid were measured before operation and at 6, 12, and 18 months after operation in the experimental group using ELISA method; the levels in plasma were measured in control group. Results: Primary healing of incisions was achieved in patients. All patients were followed up 18 24 months (mean, 21 months). The X-ray film showed osseous healing at osteotomy site at 9-14 weeks (mean, 11.5 weeks). The average tibiofemoral angle was 167.5 degrees (range, 165-170 degrees ) after bone healing. Satisfactory limb alignment was obtained in all patients. The postoperative VAS pain score was significantly decreased and KSS score was significantly improved when compared with preoperative scores ( P<0.05), but no significant difference was found between different time points after operation ( P>0.05). The preoperative plasma and synovial fluid IL-1beta, IL-6, and IL-17 concentrations were significantly higher in patients than controls ( P<0.05). The postoperative IL-1beta, IL-6, and IL-17 concentrations in plasma and synovial fluid were significantly lower than preoperative ones in patients ( P<0.05), but the concentrations were significantly higher than those in controls ( P<0.05). The postoperative plasma and synovial fluid IL-1beta, IL-6, and IL-17 concentrations were significantly declined in patients, but there was no significant difference between different time points after operation ( P>0.05). Conclusion: HTO can significantly improve the pain symptom and joint function and reduce IL-1beta, IL-6, and IL-17 levels in both plasma and synovial fluid of patients with medial compartment knee OA, but these cytokines can not return to normal level. PMID- 29798607 TI - [Effectiveness of anterior talofibular ligament repair in treatment of lateral ankle stability]. AB - Objective: To evaluate the effectiveness of anterior talofibular ligament repair in the treatment of lateral ankle stability and the effect of combined tarsal sinus syndrome on results. Methods: Between December 2013 and October 2014, 47 cases of lateral ankle instability underwent anatomical repair of anterior talofibular ligament, and the clinical data were retrospectively analyzed. Of 47 cases, 32 had no tarsal sinus syndrome (group A); 15 had tarsal sinus syndrome (group B), arthroscopic debridement of tarsal sinus was performed at the same time. There was no significant difference in gender, age, disease duration, side, American Orthopaedic Foot and Ankle Society (AOFAS), Karlsson score, and Tegner movement function score between 2 groups ( P>0.05). Results: No early surgical complication of infection occurred, and primary healing of incision was obtained in 2 groups. The patients were followed up 20-31 months (mean, 26.0 months) in group A, and 20-31 months (mean, 24.7 months) in group B. Disappearance of ankle swelling, good joints movement, and recovery of normal walking were observed in all patients. At last follow-up, AOFAS score, Karlsson score, and Tegner movement function score were significantly improved when compared with preoperative ones in 2 groups ( P<0.05), but no significant difference was found between 2 groups ( P>0.05). No ankle instability recurrence was found during follow-up period. Conclusion: The effectiveness of anatomical repair of anterior talofibular ligament in lateral ankle instability is satisfactory for patients with or without tarsal sinus syndrome. PMID- 29798608 TI - [Curative analysis of individual surgery for chronic Achilles tendon rupture]. AB - Objective: To investigate the effectiveness of individual surgery for chronic Achilles tendon rupture. Methods: A retrospective analysis was made on the clinical data of 25 patients (26 Achilles tendons) with chronic Achilles tendon rupture between September 2009 and March 2016, including 22 males and 3 females with a mean age of 38 years (range,18-59 years). The median disease duration was 12 weeks (range, 4 weeks to 12 years). The repairing method depended on the defect size, injury site, and tissue condition of the involved Achilles tendon: 9 Achilles tendons were repaired by end-to-end anastomosis, 8 by a gastrocnemius turndown flap, and 9 by auto free tendon (4 ipsilateral hamstring tendon and 5 ipsilateral 2/3 peroneus longus tendon). The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hind foot score, heel lifting of the affected leg, active ankle range of motion (plantar flexion and dorsiflexion), maximum calf circumference, and complications were applied to assess the effectiveness. Results: Hypersensitivity occurred in 1 incision, and stage I healing was obtained in the other incisions. No complication of re-rupture, infection, nerve injury, or deep venous thrombosis occurred. All the patients were followed up 8 85 months (mean, 34 months). The AOFAS ankle-hind foot score was significantly improved to 95.81+/-5.34 at last follow-up from preoperative 50.54+/-5.52 ( t= 34.844, P=0.000); the excellent and good rate was 100% (excellent in 21 cases and good in 4 cases). The active dorsiflexion of the operated side [(13.9+/-2.4) degrees ] was significantly lower than that of normal side [(16.7+/-2.0) degrees ] ( t=-9.099, P=0.000), but the active plantar flexion showed no significant difference between affected side [(39.8+/- 3.2) degrees ] and normal side [(40.6+/-2.6 degrees )] ( t=-1.917, P=0.068). The maximum calf circumference of the operated side [(379.4+/-18.8) mm] was significantly lower than that of normal side [(387.1+/-16.6) cm] ( t=-5.053, P=0.000). The other patients could finish heel lifting of the affected leg without limitation except for 1 patient. All patients returned to normal work and activity, and 12 patients returned to normal sports. Conclusion: Individual surgery depending on the defect, injury site, and tissue condition of the involved Achilles tendon can repair all kinds of chronic Achilles tendon rupture with a low rate of complications. PMID- 29798609 TI - [Research of enhanced green fluorescent protein gene transfer with ultrasound mediated microbubble destruction in bone defects]. AB - Objective: To investigate the effect of ultrasonic irradiation time on enhanced green fluorescent protein (EGFP) gene transfection efficiency and local tissue in bone defects using ultrasound-mediated microbubble destruction. Methods: Thirty 3 month-old New Zealand rabbits (2.5-3.0 kg in weight) were randomly divided into 5 groups ( n=6) and bone defect models were made on the right ulna. At 10 days after modeling, suspension of microbubbles and EGFP plasmids were locally injected (0.3 mL/kg) and then ultrasound was performed on defect at a frequency of 1 MHz, a intensity of 0.5 W/cm 2, and a duty ratio of 20% for 1, 2, 3, 4, and 5 minutes respectively (in 1, 2, 3, 4, and 5 minutes groups respectively). The survival condition was observed. Rabbits were sacrificed for gross observation at 7 days after transfer. The gene expression was observed by fluorescence staining. HE staining and transmission electron microscopy were used to observe the local tissue damage. Results: The animals all survived. New soft tissue formed in bone defects area at 1 week after transfer, the surrounding muscle tissue was partly filled in it. Green fluorescence expression was observed in all rabbits. The expression was the strongest in 2 minutes group, and was the weakest in 1 minute group. The absorbance ( A) value showed significant differences when compared 1 minute and 2 minutes groups with other groups ( P<0.05), but no significant difference was found between 3, 4, and 5 minutes groups ( P>0.05). Tissue damage was observed in all groups and it was aggravated with the increase of irradiation time. Conclusion: EGFP transfection efficiency in bone defect by ultrasound mediated microbubble destruction is related to irradiation time. EGFP gene can be efficiently transfected without obvious toxicity at 1 MHz, 0.5W/cm 2, and duty ratio of 20% for 2 minutes in bone defects of rabbits. PMID- 29798610 TI - [Domestic artificial cervical disc interface pressure distribution and effect of bone-implant interface pressure on osseointegration]. AB - Objective: To analyze the distribution of stress in the upper and lower plates of the prosthesis-bone interface, and the effect of interface pressure on osseointegration. Methods: CT scanning was performed on goats at 1 week after artificial cervical disc replacement to establish the finite element model of C 3, 4. The stress distribution of the upper and lower plates of the interface was observed. At 6 and 12 months after replacement, Micro-CT scan and three dimensional reconstruction were performed to measure the bone volume fraction (BVF), trabecular number (Tb. N), trabecular thickness (Tb. Th), trabecular separation (Tb. Sp), bone mineral density (BMD), bone surface/bone volume (BS/BV), and trabecular pattern factor (Tb. Pf). The C 3 lower plate and C 4 upper plate of 4 normal goat were chosen to made the cylinder of the diameter of 2 mm. The gene expressions of receptor activator for nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), transforming growth factor beta (TGF-beta), and macrophage colony-stimulating factor (M-CSF) were detected by real time fluorescent quantitative PCR at immediate after cutting and at 24 and 48 hours after culture. The samples of appropriate culture time were selected to made mechanical loading, and the gene expressions of RANKL, OPG, M-CSF, and TGF-beta were detected by real time fluorescent quantitative PCR; no mechanical loading samples were used as normal controls. Results: Under 25 N axial loading, the stress of the upper plate of C 3, 4 was concentrated to post median region, and the stress of the lower plate to middle-front region and two orbits. According to stress, the plate was divided into 5 regions. The Micro-CT scan showed that BMD, Tb.Th, BVF, and Tb.N significantly increased, and BS/BV, Tb.Sp, and Tb.Pf significantly decreased at 12 months after replacement when compared with ones at 6 months ( P<0.05). At 24 and 48 hours after culture, the gene expressions of RANKL, OPG, and TGF-beta were signifi-cantly higher than those at immediate ( P<0.05), but no significant difference was found between at 24 and 48 hours after culture ( P>0.05). The mechanical loading test results at 24 hours after culture showed that the RANKL and OPG gene expressions and OPG/RANKL ratio in C 3 lower plate and C 4 upper plate were significantly up-regulated when compared with controls ( P<0.05), but no significant difference was shown in TGF-beta and M-CSF gene expressions ( P>0.05). Conclusion: Domestic artificial cervical disc endplate has different pressure distribution, the stress of lower plate is higher than that of upper plate. Pressure has important effect on local osseointegration; the higher pressure area is, the osseointegration is better. Under the maximum pressure in interface, the osteoblast proliferation will increase, which is advantageous to the local osseointegration. PMID- 29798611 TI - [Analysis of cervical sagittal parameters on MRI in patients with cervical spondylotic myelopathy]. AB - Objective: To analyse the correlation between cervical sagittal parameters of cervical spondylotic myelopathy in different sagittal curvature so as to find out representative cervical sagittal alignment parameters by measuring on MRI. Methods: A retrospective analysis was made on the clinical data of 88 patients with cervical spondylotic myelopathy between July 2015 and January 2016. The C 2 C 7 Cobb angle, T 1 slope (T 1S), and C 2-C 7 sagittal vertical axis (C 2-C 7 SVA) were measured on T2-weight MRI. According to C 2-C 7 Cobb angle, the patients were divided into lordosis group (>=10 degrees Cobb angle, 48 cases) and straightened group (0-10 degrees Cobb angle, 40 cases). Intraclass correlation coefficient (ICC) was used for the reliability of measured data, Pearson correlation analysis for correlation between cervical sagittal parameters. Results: ICC was 0.858-0.946, indicating good consistency of measurement parameters. The C 2-C 7 Cobb angle, T 1S, and C 2-C 7 SVA were (5.6+/ 2.4) degrees , (22.2+/-6.7) degrees , and (10.2+/-5.4) mm in straightened group, and were (20.1+/-8.2) degrees , (23.4+/-8.9) degrees , and (8.2+/-4.6) mm in lordosis group respectively. There was no correlation between the 3 parameters in straighten group ( r=0.100, P=0.510 for T 1S and C 2-C 7 Cobb angle; r=-0.100, P=0.500 for T 1S and C 2-C 7 SVA; r=0.080, P=0.610 for C 2-C 7 Cobb angle and C 2 C 7 SVA). There was positive correlation between T 1S and C 2-C 7 Cobb angle ( r=0.540, P=0.000), negative correlation between T 1S and C 2-C 7 SVA ( r=-0.450, P=0.001), and no correlation between C 2-C 7 Cobb angle and C 2-C 7 SVA ( r= 0.003, P=0.980). Conclusion: For cervical spondylotic myelopathy in patients with cervical lordosis, only T 1S measurement on MRI can be used as the main parameter to judge the sagittal curvature, but in patients with straightened cervical Cobb angle, measurements of T 1S, C 2-C 7 Cobb angle, and C 2-C 7 SVA should be taken for the comprehensive evaluation of cervical sagittal curvature. PMID- 29798612 TI - [Extreme lateral channel debridement and fusion combined with posterior fixation for lumbar spinal tuberculosis]. AB - Objective: To investigate the effectiveness of extreme lateral channel debridement and fusion combined with posterior fixation for lumbar spinal tuberculosis. Methods: A retrospective analysis was made on the clinical data of 17 patients with lumbar spinal tuberculosis undergoing extreme lateral channel debridement and fusion combined with posterior fixation between December 2008 and December 2014. There were 10 males and 7 females, aged 20-69 years (mean, 42.6 years). The disease duration was 1-6 months (mean, 3.4 months). The involved segments included L 1, 2 in 5 patients, L 2, 3 in 6 patients, L 3, 4 in 3 patients, and L 4, 5 in 3 patients. Based on American Spinal Injury Association (ASIA) classification, there were 2 cases of grade C, 13 cases of grade D, and 2 cases of grade E. The visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Barthel index were used to evaluate the effectiveness, and the improvement rate of JOA score and Barthel index was calculated at the same time. Lumbar X-ray film and CT were taken regularly to evaluate lumbar kyphotic Cobb angle correction and bony fusion. Results: The operation was successfully performed in 17 patients, and pathological examination showed tuberculosis. All cases were followed up 24-48 months (mean, 35.3 months). Lumbar X-ray film and CT showed that necrotic bone and abscess were cleared completely, and lumbar kyphosis correction was satisfactorily in all cases. Bony fusion was achieved within 6 months, and clinical cure was obtained within 18 months in all cases; no recurrence was found during follow-up period. No loosening or breakage of internal fixation was observed. At last follow-up, ASIA classification was recovered to grade D and grade E from grade C in 2 cases, to grade E from grade D in 11 cases and had no change in 2 cases (grade D). Two cases of ASIA grade E showed no neurological deficit. The VAS score, JOA score, Barthel index, and lumbar kyphotic Cobb angle were significantly improved at 2 weeks after operation and at last follow-up when compared with preoperative ones ( P<0.05). At last follow-up, the improvement rate of JOA score was 75.2%+/-6.2% and the improvement rate of Barthel index was 75.7%+/-10.8%. Conclusion: To use extreme lateral channel debridement and fusion combined with posterior fixation is an effective treatment for lumbar spinal tuberculosis. PMID- 29798613 TI - [Effect of facial artery musculo-mucosal flap in reconstructing defects of tongue and mouth floor]. AB - Objective: To explore the effect of facial artery musculo-mucosal (FAMM) flap to reconstruct tongue and floor of mouth defects. Methods: Between January 2011 and January 2016, 24 cases of tongue and floor of mouth defects were repaired with FAMM flap after tumor resection. There were 16 males and 8 females, aged from 38 to 70 years with an average of 55 years. The disease duration was from 1 week to 6 months with an average of 4 months. The defect located at the floor of mouth in 4 cases, at the tongue in 15 cases, and both tongue and floor of mouth in 5 cases. There were 2 cases of carcinoma at the floor of mouth, 2 cases of adenoid cystic carcinoma at the floor of mouth, 14 cases of carcinoma at the tongue, 1 case of adenoid cystic carcinoma at the tongue, and 5 cases of carcinoma at the tongue and floor of mouth. The size of defect ranged from 4 cm*3 cm to 8 cm*7 cm. Three ipsilateral and 21 contralateral FAMM flaps were harvested (5 cases were repaired with FAMM flap and submental muscle island flap due to the large defect area). The size of FAMM flap ranged from 5 cm*4 cm to 5 cm*5 cm, the size of submental muscle island flap ranged from 4 cm*3 cm to 5 cm*4 cm. Results: All flaps survived after operation, without local necrosis. Wound dehiscence at donor site occurred in 5 cases, and healed after cleaning; primary healing was obtained in the other 19 cases. All the patients were followed up 8 months to 5 years with an average of 2 years and 4 months. No obvious facial deformity or fistula of the floor of mouth occurred after operation. Injury of the submandibular branch of the facial nerve was observed in 16 patients, who returned to normal at 3 months. All 24 patients had limitation of mouth opening after operation, which disappeared after 12 months. The functions of speech, chewing, and swallowing were normal. Conclusion: FAMM flap has many advantages of simple operation, good repair, high flap survival rate, and less injury at donor site for repairing tongue and floor of mouth defects. PMID- 29798614 TI - [Effect of tranilast on wound healing and administration time on scar hyperplasia of deep partial-thickness burn in mice]. AB - Objective: To investigate the effect of tranilast on wound healing and the mechanism of inhibiting scar hyperplasia in mice, and to study the relationship between the inhibiting ability of tranilast on scar hyperplasia and administration time. Methods: Sixty-six Kunming mice were selected to build deep II degree burn model, and were randomly divided into the control group (18 mice), the early intervention group (18 mice), the medium intervention group (18 mice), and the late intervention group (12 mice). The mice in the early intervention group, the medium-term intervention group, and the late intervention group were given tranilast 200 mg/(kg.d) by gastrogavage at immediate, 7 days, and 14 days after burn respectively, and the mice in the control group were managed with same amount of normal saline every day. The wound healing was observed regularly. At 14, 28, and 42 days in the early and medium intervention groups and at 28 and 42 days in the late intervention group, fresh tissues were taken from 6 mice to observe the shape of mast cells by toluidine blue staining, collagen content by Masson staining; the collagen type I and collagen type III content were measured to calculate the I/III collagen content ratio by immunohistochemistry method, the contents of transforming growth factor beta 1 (TGF-beta 1) and histamine were detected by ELISA; and the ultrastructure of fibroblasts was observed under transmission electron microscope. Results: There was no significant difference in wound healing time between groups ( F=1.105, P=0.371). The mast cells number, collagen content, TGF-beta 1 content, histamine content, and the I/III collagen content ratio in the early intervention group were significantly less than those in the other groups ( P<0.05). Significant difference was found in mast cells number, collagen content, and histamine content between control group and medium or late intervention group at the other time points ( P<0.05) except between control group and late intervention group at 42 days ( P>0.05). Compared with the control group, the activity of fibroblasts in the early intervention group was obviously inhibited, and the arrangement of the fibers was more regular; the fibroblast activity in the medium and late intervention groups was also inhibited obviously. Conclusion: Tranilast has no obvious effect on the wound healing time in mice. Tranilast intervention shows the inhibitory effect on the scar hyperplasia which can significantly reduce the number of mast cells, the content of histamine and TGF-beta 1, inhibit the ability of fibroblasts synthetic collagen and adjust the proportion of collagen synthesis. The immediate tranilast intervention may have the best inhibitory effect on scar hyperplasia. PMID- 29798616 TI - [Effects of different mechanical stretch conditions on differentiation of rat tendon stem cells]. AB - Objective: To investigate the effects of different mechanical stretch conditions on the differentiation of rat tendon stem cells (TSCs), to find the best uniaxial cyclic stretching for TSCs tenogenic differentiation, osteogenic differentiation, and adipogenic differentiation. Methods: TSCs were isolated from the Achilles tendons of 8-week-old male Sprague Dawley rats by enzymatic digestion method and cultured. The TSCs at passage 3 were randomly divided into 5 groups: group A (stretch strength of 4% and frequency of 1 Hz), group B (stretch strength of 4% and frequency of 2 Hz), group C (stretch strength of 8% and frequency of 1 Hz), group D (stretch strength of 8% and frequency of 2 Hz), and group E (static culture). At 12, 24, and 48 hours after mechanical stretch, the mRNA expressions of the tenogenic differentiation related genes [Scleraxis (SCX) and Tenascin C (TNC)], the osteogenic differentiation related genes [runt related transcription factor 2 (RUNX2) and distal-less homeobox 5 (DLX5)], and the adipogenic differentiation related genes [CCAAT-enhancer-binding protein-alpha (CEBPalpha) and lipoprteinlipase (LPL)] were detected by real-time fluorescent quantitative PCR and the protein expressions of TNC, CEBPalpha, and RUNX2 were detected by Western blot. Results: The mRNA expressions of SCX and TNC in group B were significantly higher than those in groups A, C, D, and E at 24 hours after mechanical stretch ( P<0.05). The mRNA expressions of CEBPalpha and LPL in group D were significantly higher than those in groups A, B, C, and E at 48 hours after mechanical stretch ( P<0.05). The mRNA expressions of RUNX2 and DLX5 in group C were significantly higher than those in groups A, B, D, and E at 24 hours after mechanical stretch ( P<0.05). Western blot detection showed that higher protein expression of TNC in group B than group E at each time point after mechanical stretch ( P<0.05), and the protein expression of CEBPalpha was significantly inhibited when compared with group E at 24 hours after mechanical stretch ( P<0.05). At 24 hours after mechanical stretch, the protein expression of RUNX2 in group C was significantly higher than that in group E ( P<0.05); and the protein expression of TNC was significantly lower than that in group E at 24 and 48 hours after mechanical stretch ( P<0.05). At 48 hours after mechanical stretch, the protein expression of CEBPalpha was significantly increased and the protein expression of TNC was significantly decreased in group D when compared with group E ( P<0.05), but no significant difference was found in the protein expression of RUNX2 between groups D and E ( P>0.05). Conclusion: The mechanical strain could promote differentiation of TSCs, and different parameter of stretch will lead to different differentiation. The best stretch condition for tenogenic differentiation is 4% strength and 2 Hz frequency for 24 hours; the best stretch condition for osteogenic differentiation is 8% strength and 1 Hz frequency for 24 hours; and the best stretch condition for adipogenic differentiation is 8% strength and 2 Hz frequency for 48 hours. PMID- 29798615 TI - [Comparison of biological characteristics between bone marrow mesenchymal stem cells and anterior cruciate ligament derived mesenchymal stem cells in rats]. AB - Objective: To compare the biological characteristics of bone marrow mesenchymal stem cells (BMSCs) and anterior cruciate ligament derived mesenchymal stem cells (ACL-MSCs) from rats in vitro. Methods: Ten male SPF-level BN rats, weighing 200 220 g, were selected to obtain anterior cruciate ligaments and bone marrows, and ACL-MSCs and BMSCs were isolated for passage culture respectively under sterile condition. The cell morphology was observed, and the cells at passage 3 were used to detect the surface markers of CD34, CD45, CD90, and CD29 by flow cytometry, the ability of cell proliferation by cell counting kit 8 (CCK-8), and colony formation ability by clone forming test. The mRNA levels of differentiation related genes [alkaline phosphatas (ALP), bone gamma-carboxyglutamate protein, runt related transcription factor 2, bone morphogenetic protein 2 (BMP-2), secreted phosphoprotein 1 (Spp1), collagen type II alpha1 (Col2alpha1), Aggrecan (Acan), Sox9, peroxisome proliferator activated receptor gamma2 (PPARgamma2), and CCAAT-enhancer-binding protein-alpha] were also determined by real-time fluorescent quantitative PCR. Results: BMSCs and ACL-MSCs had similar morphology, adherent cells displaying long fusiform. The immunoprofile of ACL-MSCs and BMSCs at passage 3 was positive for CD29 and CD90 and was negative for CD45 and CD34. The absorbance ( A) value of ACL-MSCs (1.11+/-0.08) was significantly higher than that of BMSCs (0.78+/-0.05) ( t=3.599, P=0.023); the number of colonies of ACL MSCs [(53.00+/-5.51)/hole] was significantly more than that of BMSCs [(30.67+/ 4.84)/hole] ( t=3.045, P=0.038). The results of toluidine blue staining, alizarin red staining, and oil red O staining were positive in BMSCs and ACL-MSCs at 21 days after osteogenic, chondrogenic, and adipogenic induction. The mRNA expressions of BMP-2, Spp1, Col2alpha1, Acan, Sox9, and PPARgamma2 in ACL-MSCs were significantly higher than those in BMSCs ( P<0.01). Conclusion: The proliferation potential of ACL-MSCs is greater than that of BMSCs, and the former is apt to differentiate into chondrocytes. ACL-MSCs are promising cells to promote tendon-bone healing. PMID- 29798617 TI - [Experimental study on loading naringin composite scaffolds for repairing rabbit osteochondral defects]. AB - Objective: To investigate the performance of loading naringin composite scaffolds and its effects on repair of osteochondral defects. Methods: The loading naringin and unloading naringin sustained release microspheres were prepared by W/O/W method; with the materials of the attpulgite and the collagen type I, the loading naringin, unloading naringin, and loading transforming growth factor beta 1 (TGF beta 1) osteochondral composite scaffolds were constructed respectively by "3 layers sandwich method". The effect of sustained-release of loading naringin microspheres, the morphology of the composite scaffolds, and the biocompatibility were evaluated respectively by releasing in vitro, scanning electron microscope, and cell counting kit 8. Forty Japanese white rabbits were randomly divided into groups A, B, C, and D, 10 rabbits each group. After a osteochondral defect of 4.5 mm in diameter and 4 mm in depth was made in the intercondylar fossa of two femurs. Defect was not repaired in group A (blank control), and defect was repaired with unloading naringin composite scaffolds (negative control group), loading naringin composite scaffolds (experimental group), and loading TGF-beta 1 composite scaffolds (positive control group) in groups B, C, and D respectively. At 3 and 6 months after repair, the intercondylar fossa was harvested for the general, HE staining, and toluidine blue staining to observe the repair effect. Western blot was used to detect the expression of collagen type II in the new cartilage. Results: Loading naringin microspheres had good effect of sustained release; the osteochondral composite scaffolds had good porosity; the cell proliferation rate on loading naringin composite scaffold was increased significantly when compared with unloading naringin scaffold ( P<0.05). General observation revealed that defect range of groups C and D was reduced significantly when compared with groups A and B at 3 months after repair; at 6 months after repair, defects of group C were covered by new cartilage, and new cartilage well integrated with the adjacent cartilage in group D. The results of histological staining revealed that defects were filled with a small amount of fibrous tissue in groups A and B, and a small amount of new cartilage in groups C and D at 3 months after repair; new cartilage of groups C and D was similar to normal cartilage, but defects were filled with a large amount of fibrous tissue in groups A and B at 6 months after repair. The expression of collagen type II in groups C and D was significantly higher than that in groups A and B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). Conclusion: Loading naringin composite scaffolds have good biocompatibility and effect in repair of rabbit articular osteochondral defects. PMID- 29798618 TI - [Research progress and clinical prospect of three-dimensional spheroid culture of mesenchymal stem cells]. AB - Objective: To review the research progress and clinical prospect of three dimensional spheroid culture of mesenchymal stem cells (MSCs). Methods: Recent literature about three-dimensional spheroid culture of MSCs was summarized, mainly on the formation of MSCs spheroids collected by three-dimensional culture, differences between MSCs spheroids and MSCs collected by traditional two dimensional culture, and the mechanism underlying these differences. Last, its clinical prospect was discussed. Results: Compared with MSCs collected by traditional two-dimensional culture, MSCs spheroids collected by three dimensional culture get a salient up-regulation in anti-apoptosis, multiple differentiation potential, paracrine, and anti-inflammatory effect, which may be related to the morphology and cytoskeleton organization, cell-to-cell contact and gap junctions, and the hypoxia microenvironment. The animal experiments show obvious effects in repair of refractory wounds, repair of ischemic injury, and tissue remodeling, so MSCs spheroid has broad clinical prospect. Conclusion: MSCs spheroids collected by three-dimensional culture have stronger biological potential and treatment effect than MSCs collected by traditional two-dimensional culture, MSCs spheroids can be used to optimize stem cell therapy and improve its treatment effect. PMID- 29798619 TI - [Application progress of surface electromyography and surface electromygraphic biofeedback in low back pain]. AB - Objective: To summarize the application progress of surface electromyography (sEMG) and surface electromygraphic biofeedback (sEMGBF) in low back pain (LBP). Methods: The related literature about the application of sEMG and sEMGBF in diagnosis and therapy of LBP was summarized and analyzed. Results: As a auxiliary diagnostic technique, lumbar muscle fatigue, lumbar muscle activity disorder, flexion-relaxation phenomenon, and asymmetry of the paravertebral muscle electromygraphic activity were found in patients with LBP by sEMG. For treatment, sEMG combined with sEMGBF technology to form sEMGBF training. sEMGBF training include sEMGBF training and sEMGBF stretching exercise. sEMGBF training can improve lumbar muscle activity disorder, recover muscle function, and relieve back pain. Conclusion: sEMG can monitor the electromyographic signal and sEMGBF biofeedback information can relax or strengthen the muscle. It is very meaningful for diagnosis and therapy of LBP. PMID- 29798620 TI - [Effectiveness of locking compress plate and extra cortical bone bridge fixation for treatment of atrophic humeral nonunions]. AB - Objective: To assess the effectiveness of locking compress plate and extra cortical bone bridge fixation for treating atrophic humeral nonunion. Methods: Seventeen patients with atrophic humeral nonuninon were treated with locking compress plate and extra cortical bone bridge fixation between November 2006 and June 2015. Of 17 cases, 11 were male, 6 were female, aged 24-63 years (mean, 38.2 years). Fracture located at the left side in 9 cases and at the right side in 8 cases. The mechanism of injury was traffic accident in 13 cases, falling from height in 3 cases, and heavy pound injury in 1 case. The patients underwent surgery for 1 time in 7 cases, for 2 times in 5 cases, for 3 times in 4 cases, and for 4 times in 1 case. The time from fracture to hospitalization was 10-76 months (mean, 22.6 months). The shoulder function was evaluated by Neer score, and elbow function by Mayo score. Results: All incisions healed by first intention. Two cases had transient radial nerve symptoms of numbness. All patients were followed up 27.3 months on average (range, 15-60 months). Radiographic examination showed signs of bone remodeling at 6-8 weeks after operation, and formation of extra cortical bone bridge. All of them achieved bone union within 10 to 41 weeks (mean, 17.6 weeks). At last follow-up, the average Neer score was 83.36 (range, 72-96); and the shoulder function was excellent in 10 cases, good in 5, and fair in 2 with an excellent and good rate of 88.24%. And the average Mayo score was 86.52 (range, 68-100); and the elbow function was excellent in 11 cases, good in 3, and fair in 3 with an excellent and good rate of 82.35%. Conclusion: The bone bridging could effectively form by extra cortical grafting technique. Atrophic humeral nonunions can be successfully treated with locking compress plate and extra cortical bone bridge fixation. PMID- 29798621 TI - [Short-term effectiveness of polyaxial locking plate for fixation of femoral neck fracture in middle-aged and elderly patients]. AB - Objective: To evaluate the feasibility and short-term effectiveness of polyaxial locking plate for fixation of femoral neck fracture in the middle-aged and elderly patients. Methods: A retrospective analysis was made on the clinical data of 13 patients with femoral neck fracture undergoing fixation with polyaxial locking plates between September 2013 and June 2015 (group A) and 13 patients with femoral neck fracture undergoing fixation with three cannulated screws in the same period (group B). There was no significant difference in gender, age, side, cause of injury, Garden type, type of fracture position, type of Pauwels angle, Singh index, time between injury and operation, and preoperative complications between 2 groups ( P>0.05). The femoral neck shortening at 1 year postoperatively, and fracture nonunion, femoral head necrosis, and Harris hip score at last follow-up were compared between 2 groups. Results: The follow-up time was (19.23+/-3.98) months in group A and (18.00+/-3.61) months in group B, showing no significant difference between 2 groups ( t=2.063, P=0.417). No femoral head necrosis occurred in group A, but head necrosis occurred in 1 case of group B, and hemiarthroplasty was performed. There was no significant difference in the rate of femoral head necrosis between 2 groups ( chi2=0.000, P=1.000). Bone union was obtained in the other patients of 2 groups. The Harris hip score of group A (85.23+/-2.95) was significantly higher than that of group B (81.92+/-3.64) at last follow-up ( t=2.064, P=0.018). No infection or internal fixation failure occurred in 2 groups. One case had pain at the outer thigh at 1 month after operation in group A, but pain relief was achieved at 3 months after operation. At 1 year after operation, no femoral neck shortening occurred in group A, but degree I, II, and III femoral neck shortening was observed in 3, 2, and 8 cases of group B, respectively, showing significant difference between 2 groups ( Z=-4.714, P=0.000). Conclusion: Although fixation with polyaxial locking plate for femoral neck fracture in the middle-aged and elderly patients has similar femoral head necrosis rate to fixation with cannulated screws, it has advantages in preventing neck shortening and improving hip joint function after operation. PMID- 29798622 TI - [Short-term effectiveness of minimally invasive total hip arthroplasty by direct anterior approach]. AB - Objective: To evaluate the short-term effectiveness of minimally invasive total hip arthroplasty (THA) by direct anterior approach (DAA). Methods: Between January and August 2014, THA was performed on 48 patients (60 hips) by DAA (group A), and on 72 patients (92 hips) by posterolateral approach (group B). There was no significant difference in gender, age, etiology, course, and preoperative visual analogue scale (VAS), Harris hip score (HHS), and hip range of motion (ROM) between 2 groups ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage, hospitalization time, incision healing, and complications were recorded and compared. The acetabular abduction and anteversion were measured on the X-ray films; prosthesis loosening was observed. The VAS score, HHS score, and hip ROM were used to evaluate the hip function. Results: The operation time and intraoperative blood loss of group A were significantly higher than those of group B, and the hospitalization time was significantly lower than group B ( P<0.05), but no significant difference was found in postoperative drainage between 2 groups ( t=0.71, P=0.46). The patients were followed up 2-2.5 years (mean, 2.2 years) in group A, and 2-2.5 years (mean, 2.1 years) in group B. In group A, 3 cases had lateral femoral cutaneous nerve traction injury and 1 case had swelling and exudate, and primary healing of incision was obtained in the other cases of group A and all cases of group B. No periprosthetic joint infection occurred in the others of groups A and B except 1 case of group A at 2 months after operation, and infection was controlled after debridement, irrigation, and intravenous infusion of Vancomycin for 1 month. The X-ray films showed good position of prosthesis and no obvious radiolucent line or prosthesis loosening. There was no significant differences in acetabular abduction and anteversion between groups A and B at last follow-up ( P>0.05). The VAS score, HHS score, and hip ROM at 3 months and last follow-up were significantly better than preoperative ones in 2 groups ( P<0.05), but no significant difference was found between at 3 months and last follow-up ( P>0.05). The VAS score, HHS score, and hip ROM in group A were significantly better than those in group B at 3 months postoperatively ( P<0.05). At last follow-up, the hip ROM in group A was significantly better than that in group B ( P<0.05), and there was no significant difference in VAS and HHS scores between group A and group B ( P>0.05). Conclusion: The short-term effectiveness of minimally invasive THA by DAA is satisfactory, with the advantage of little trauma, short hospital stay, and rapid postoperative recovery. PMID- 29798623 TI - [Comparison of early effectiveness between SuperPATH approach and Hardinge approach in total hip arthroplasty]. AB - Objective: To compare the early effectiveness between SuperPATH approach and traditional Hardinge approach in total hip arthroplasty (THA). Methods: Between May 2015 and March 2016, 154 patients (173 hips) undergoing initial THA were included. THA was performed by SuperPATH approach in 64 cases (70 hips) in group A and by traditional Hardinge approach in 90 cases (103 hips) in group B. There was no significant difference in gender, age, body mass index, type of disease, and Harris hip score (HHS) between 2 groups ( P>0.05). The incision length, operation time, intraoperative blood loss, postoperative drainage volume, transfusion rate, ambulation time, length of stay, and complications were recorded. The HHS and visual analogue scale (VAS) were compared between 2 groups before operation and at 1 day, 3 days, 1 week, 3 weeks, 6 weeks, 12 weeks, and 24 weeks after operation. And the relative parameters were measured for imaging evaluation of prosthesis position. In addition, the stratification analysis was performed on 92 patients (100 hips) who received the SuperPATH technology. Results: The incision length, ambulation time, and length of stay in group A were significantly less than those in group B ( P<0.05); the operation time, transfusion rate, and intraoperative blood loss of group A were significantly higher than those of group B ( P<0.05); and there was no significant difference in postoperative drainage volume between 2 groups ( t=1.901, P=0.071). The follow up period was 6 to 15 months (mean, 9 months). The VAS scores at 1 day, 3 days, and 1 week after operation in group A were significantly lower than those in group B ( P<0.05), but the HHS scores at 1 day, 3 days, 1 week, and 3 weeks after operation in group A were significantly higher than those in group B ( P<0.05). At 24 weeks after operation, the acetabular cup abduction and the proportion within the safe zone showed no significant difference between 2 groups ( P>0.05); the anteversion angle and limb length difference in group A were significantly greater than those in group B ( P<0.05), and the proportion of anteversion angle within the safe zone and eccentricity and recovery rate were significantly lower than those in group B ( P<0.05). In the stratification analysis, the operation time, incision length, intraoperative blood loss, transfusion rate, and VAS score at 1 day after operation in the former 30 hips were significantly higher than those in the latter 70 hips ( P<0.05). Great trochantern fracture and dislocation of the hip joint occurred in 1 and 2 of the former 30 hips, but no complications occurred in the latter 70 hips. No injury of nerve or blood vessel, deep vein thrombosis, infection, and prosthetic loosening were observed in the 2 groups. Conclusion: Compared with the Hardinge approach, the SuperPATH approach shows the advantages in little trauma, fast recovery, satisfactory effectiveness, and slight early postoperative pain, but it shows the disadvantages of much intraoperative blood loss and long operation time. In addition, SuperPATH approach needs a more anteverted angle, a smaller eccentricity, and a learning curve, so the mid-term and long-term outcomes still need further follow-up study. PMID- 29798624 TI - [Effectiveness of total hip arthroplasty in the treatment of involved hips in patients with ankylosing spondylitis]. AB - Objective: To summarize the mid- to long-term effectiveness of total hip arthroplasty (THA) in the treatment of the involved hips in patients with ankylosing spondylitis (AS), and to investigate its influencing factors. Methods: Between March 1999 and May 2011, 32 patients (42 hips) with AS and involved hip underwent THA. There were 26 males and 6 females with a mean age of 39 years (range, 20-78 years). The disease duration ranged from 2 to 41 years, with a median of 10 years. Metal-on-polyethylene bearings were used in 19 hips, and ceramic-on-ceramic bearings in 23 hips. The diameter of prosthetic femoral head was 36 mm in 15 hips and was 28 mm in 27 hips; and all the prostheses were fixed biologically. The Harris score, visual analogue scale (VAS) score, and total range of motion (ROM) of the hip were compared between at pre- and post-operation to evaluate the effectiveness. The DeLee zone was used for describing acetabular prosthesis, the Gruen zone for describing femoral prosthesis, and the Brooker criterion for evaluating the heterotopic ossification. Results: Healing of incision by first intention was achieved in all patients after operation. There was no complication of anesthetic accident, infection, or neurovascular injury. Twenty-nine cases (39 hips) were followed up 5-17 years (mean, 9 years). Anterior dislocation of hip joint occurred in 2 hips of 24 hips (28 mm diameter), but did not in 15 hips (36 mm diameter). At last follow-up, the Harris score, VAS score, and the total hip ROM were significantly improved ( P<0.05). The shorter the disease duration was, the higher postoperative Harris score and the greater postoperative total hip ROM would be ( P<0.05); the bigger diameter of prosthetic femoral head was, the greater postoperative total hip ROM would be ( P<0.05). All the acetabular components and femoral stems were well fixed at last follow-up. The osteolysis rate around the acetabular cup in the metal-on-polyethylene bearing group (50%, 9/18) was higher than that in the ceramic-on-ceramic bearing group (0, 0/21). No prosthetic loosening was observed in 2 groups. Seven hips were found to have heterotopic ossification, including 5 hips of Brooker grade I and 2 hips of Brooker grade II. Conclusion: THA is an effective method to treat involved hips in patients with AS; especially for patients having shorter duration of the disease, THA shows better effectiveness when the bigger diameter of prosthetic femoral head and ceramic-on-ceramic bearing are used. PMID- 29798625 TI - [Surgical treatment of grade III pronation-external rotation fractures of ankle]. AB - Objective: To summarize the short-term effectiveness of the surgical treatment for grade III pronation-external rotation ankle fractures. Methods: Between October 2011 and May 2015, 36 patients with pronation-external rotation ankle fractures (grade III) were treated with internal fixation and repair of the anterior lower tibiofibular ligament, including 21 males and 15 females with an average age of 45.2 years (range, 21-72 years). Injury was caused by sprain in 19 cases, by traffic accident in 6 cases, and by falling from height in 11 cases. All patients had closed fractures, with no blood vessel and nerve injury. The locations were the left ankle in 13 cases and the right ankle in 23 cases. The time from injury to operation was 3 to 10 days (mean, 6.5 days). At last follow up, ankle function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) ankle-foot score, and the improvement of pain was evaluated by visual analogue scale (VAS). Results: Primary healing of incision was obtained in all patients, no incision infection and skin necrosis occurred. Twenty-eight patients were followed up 12-36 months (mean, 17.5 months). X-ray films showed bone union was achieved within 2.6-5 months (mean, 3.2 months). No fracture of internal fixation and disruption of tibiofibular diastasis occurred. At last follow-up, according to AOFAS score for ankle function evaluation, the pain score was 36.3+/ 2.9, the function score was 44.3+/-3.2, the ligament condition score was 9.2+/ 0.5, and the total score was 89.8+/-6.6; the results were excellent in 11 cases, good in 15 cases, and fair in 2 cases. VAS score was 1.6+/-0.5. The range of motion of the ankle was (13+/-5) degrees in dorsiflexion and (38+/-9) degrees in planteroflexion. Conclusion: Repair of anterior tibial ligament is an effective method to treat tibiofibular diastasis injury in the surgical treatment of grade III pronation-external rotation ankle fractures, with convenient operation, and satisfactory short-term effectiveness. PMID- 29798626 TI - [Minimally invasive treatment of calcaneal fractures by subtalar arthroscopy with posterior approach]. AB - Objective: To evaluate the results of arthroscopically-assisted closed reduction and percutaneous screw fixation by posterior approach to subtalar joint for calcaneal fractures of Essex-Lopresti tongue type, Sanders IIA, IIB, and IIIAB. Methods: Sixteen patients with unilateral calcaneal fracture were treated with arthroscopically-assisted closed reduction and percutaneous screw fixation by posterior approach to subtalar joint between June 2012 and June 2015. There were 13 males and 3 females with an average age of 37.8 years (range, 18-65 years). The injury causes included falling from height in 10 cases and traffic accident in 6 cases. Of 16 cases, 4 were classified as Essex-Lopresti tongue type, 5 as Sanders IIA, 4 as Sanders IIB, and 3 as Sanders IIIAB. The interval of injury and operation was 4-8 days (mean, 5.94 days). The Bohler angle, Gissane angle, and width of calcaneus were measured before and after operation. American Orthopaedic Foot and Ankle Society (AOFAS) score was used to evaluate the ankle function at 12 months after operation. Results: Primary healing of incision was obtained in all cases, and no complications of infection, necrosis, and osseous fascia compartment syndrome occurred. The patients were followed up 12-15 months (mean, 13.63 months). The X-ray films showed that fracture line disappeared at 6 months after operation; the patients had no tenderness or percussion pain, no breakage or loosening of internal fixation, no varus calcaneus tuberosity, no subtalar joint fusion, and no compression symptoms of peroneal tendons. Achilles tendon irritation occurred in 2 cases, and disappeared after removal of internal fixation; traumatic arthritis occurred in 2 cases, and was relieved after removal of internal fixation. The Bohler angle, Gissane angle, and calcaneal width were significantly improved at 3 days and 6 months after operation when compared with preoperative ones ( P<0.05). The loss of the above indexes was observed at 6 months, showing no significant difference between at 3 days and 6 months ( P>0.05). The AOFAS score results were excellent in 11 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 87.5%. Conclusion: It has the advantages of little trauma, less complication, and good function recovery to use arthroscopically-assited closed reduction and percutaneous screw fixation by posterior approach to subtalar joint for calcaneal fractures of Essex-Lopresti tongue type, Sanders IIA, Sanders IIB, and Sanders IIIAB. PMID- 29798627 TI - [Pre-implantation of high-intensity suture into tendon grafts to prevent postoperative graft relaxation and creep in anterior cruciate ligament reconstruction]. AB - Objective: To explore the feasibility of pre-implantation of high-intensity suture into tendon grafts to prevent postoperative graft relaxation and creep in anterior cruciate ligament (ACL) reconstruction. Methods: Thirty-six specimens of ACL reconstruction graft were made using adult swine's Achilles tendon. All the specimens were randomly divided into experimental group (groups A and C) and control group (groups B and D), 9 specimens each group. One double-strand Ultrabraid No.2 high-intensity suture was pre-implanted into the grafts of groups A and C. Groups A and B underwent a 1 000-cycles load test while groups C and D underwent a 3 000-cycles load test. Then a pull-out test was performed until failure. The displacements at different cycles (100, 500, 1 000, 2 000, and 3 000) in all groups and yield loads of groups C and D were measured and analyzed. Results: The displacement of group A was significantly smaller than that of group B at the cycles of 100, 500, and 1 000 ( P<0.05); the displacement of group C was significantly smaller than that of group D at every cycle ( P<0.05). Additionally, the yield load of group C was significantly higher than that of group D ( t=4.816, P=0.001). Conclusion: Pre-implantation of high-intensity suture into tendon grafts play an important role in the prevention of postoperative graft creep and relaxation in ACL reconstruction. PMID- 29798628 TI - [Finite element study on calcium phosphate ceramic screw implanting after removing dynamic hip screw]. AB - Objective: To investigate the validity of improving the femur's mechanical characteristics by implanting calcium phosphate ceramic screws after removing dynamic hip screw (DHS). Methods: The three dimensional finite element model of the femur was built based on the CT scanning of a normal male volunteer. Then the models of the femur with and without DHS were established. According to calcium phosphate ceramic screws with porosity and apparent elastic modulus, 80% and 0.1 GPa were set as group A, 50% and 1.0 GPa as group B, and 30% and 1.5 GPa as group C. Von Mises stress distribution and maximum stress were recorded when the joint was maximally loaded in a gait cycle. Results: The Von Mises in normal femoral shaft was uniform; no phenomena of stress concentration was observed and the maximum stress located at the joint load-bearing site of the proximal femur. The stress concentration was observed in the femur without DHS, and the maximum stress located at the distal femur around the screw hole. By comparing several different calcium phosphate ceramic screws, the stress distribution of group B was similar to normal femur model, and the maximum stress located at the joint load-bearing site. The other screws of groups A and C showed varying degrees of stress concentration. Conclusion: Implanting calcium phosphate ceramic screw can improve the mechanical characteristics of the femur after removing dynamic hip screw, and the calcium phosphate ceramic screw with 50% porosity and 1.0 GPa apparent elastic modulus is suitable for implanting. PMID- 29798629 TI - [Clinical application of relaying anteromedial thigh perforator flap in resurfacing of donor defect after anterolateral thigh flap transfer]. AB - Objective: To investigate the clinical application of relaying anteromedial thigh (AMT) perforator flap in resurfacing of the donor defect after anterolateral thigh (ALT) flap transfer. Methods: Between February 2012 and December 2015, 23 cases of oral carcinoma underwent radical resection; after resection of lesions, the tongue or mouth floor defects were reconstructed by ALT perforator flaps, and the donor sites were repaired with relaying AMT perforator flap at the same stage. There were 21 males and 2 females,with a mean age of 52.6 years (range, 29 74 years). Sixteen patients had tongue squamous cell carcinoma and 7 patients had buccal cancer. According to TNM tumor stage, 3 cases were classified as T 4N 0M 0, 5 cases as T 4N 1M 0, 7 cases as T 3N 1M 0, 5 cases as T 3N 2M 0, and 3 cases as T 3N 0M 0. The disease duration ranged from 6 to 18 months (mean, 8.8 months). Results: The AMT perforators existed consistently in all patients. All flaps survived, and primary healing of wounds was obtained at recipient sites and donor sites. No vascular crisis, wound dehiscence, or obvious swelling occurred. All patients were followed up 6-20 months (mean, 9.4 months). There was only linear scar at the donor sites, and the function of thighs was normal. The color and contour of the flaps were satisfactory. Conclusion: The relaying AMT perforator flap is an ideal choice to reconstruct the donor site of ALT flap. PMID- 29798630 TI - [A technique analysis for dissection of anterolateral thigh perforator flap]. AB - Objective: To improve the harvesting techniques of anterolateral thigh perforator flap, and to reduce the operation time. Methods: Between January 2008 and June 2015, 400 patients undergoing repair with anterolateral thigh perforator flap were included to analyze the technical factors, including 370 cases (92.5%) obtaining primary healing and 30 cases (7.5%) receiving re-exploration. Combined with the literature, a modified flap dissection was made: reverse tracing and sequential dissection of the descending branch of the lateral circumflex femoral artery. Between June 2015 and June 2016, the modified free anterolateral thigh perforator flap was used in 100 cases. Of 100 cases, 76 were male and 24 were female, aged from 11 to 71 years (mean, 35.6 years). The wound size ranged from 8 cm*5 cm to 23 cm*9 cm. The time between injury and surgery ranged from 5 to 31 days (mean, 14.3 days). Results: The operation time of modified flap dissection was reduced to (30.1+/-19.3) minutes from (85.0+/-30.2) minutes (unmodified flap dissection). Postoperatively, 94 flaps survived uneventfully, and incision healed by first intention. Six flaps received re-exploration surgery because of vascular compromise; the flap survived after removal of thrombosis in 4 cases of vein thrombosis; the flap necrosed in 2 cases of vein and artery thrombosis, and skin grafting was performed. Ninety-four patients whose flaps survived were followed up 3-12 months (mean, 6.3 months); the flaps had good color and appearance, and second stage operation was performed to make the flap thinner in 21 cases. Conclusion: Improved harvesting technique of free anterolageral thigh perforator flap could decrease surgery time and difficulty in dissection. PMID- 29798631 TI - [Clinical outcome of ISOBAR TTL dynamic stabilization with pars bone grafting for treatment of lumbar spondylolysis]. AB - Objective: To evaluate the effectiveness of ISOBAR TTL dynamic stabilization with pars bone grafting for the treatment of lumbar spondylolysis. Methods: A retrospective analysis was made the clinical data of 26 patients with lumbar spondylolysis who received ISOBAR TTL dynamic stabilization with pars bone grafting between September 2009 and March 2014. There were 14 males and 12 females, with a mean age of 31 years (range, 19-47 years). The disease duration ranged from 9 to 60 months (mean, 16 months). Preoperative lumbar anteroposterior and lateral X-ray films, CT three-dimensional reconstruction, and MRI scans were performed to identify the location of pars defect. The involved levels were L 4 in 9 cases and L 5 in 17 cases. There were 10 cases of pure spondylolysis and 16 cases of spondylolysis accompanied with I degree slipping. The clinical outcome was assessed by visual analogue scale (VAS) and Oswestry disability index (ODI) scores at preoperation and 1 week, 3 months, 6 months after operation, and at last follow-up. The lumbar CT three-dimensional reconstruction was obtained at 6 months after operation to evaluate bone fusion of the pars. The adjacent segment degeneration was assessed by the University of California at Los Angeles (UCLA) grading scale at preoperation and last follow-up. Results: All incisions healed by first intention; no infection, cerebrospinal fluid leakage, or pain at iliac crest donor site occurred. Twenty-six patients were followed up 2-5 years (mean, 36.5 months). No secondary spondylolisthesis, internal fixation loosening and breakage were found during follow-up. The postoperative VAS and ODI scores showed significant differences ( P<0.05) when compared with preoperative scores, and the scores at 3 months, 6 months, and last follow-up were significantly better than that at 1 week ( P<0.05), but no significant difference was shown between the other time points after operation ( P>0.05). The CT three-dimensional reconstruction indicated satisfactory union at the pars in 23 cases (88.5%) at 6 months after operation. Of the 3 nonunion patients, good union was obtained in 1 patient at 1 year after operation; nonunion was observed in 2 patients at last follow-up, but low back pain was obviously alleviated. According to the UCLA grading scale, 20 cases were rated as grade I and 6 cases as grade II at last follow-up, which was the same as preoperative grade and indicated no adjacent segment degeneration. Conclusion: It is safe and effective to use the ISOBAR TTL dynamic stabilization with pars bone grafting technique to treat lumbar spondylolysis with or without degree I slipping. The fusion rate is satisfactory, and adjacent segment degeneration can be slowed down after lumbar fusion surgery. PMID- 29798632 TI - [Design and clinical application of a new extracorporeal reduction device for percutaneous pedicle screw fixation in treatment of thoracolumbar fractures]. AB - Objective: To design a new extracorporeal reduction device for percutaneous pedicle screw fixation of thoracolumbar fractures (short for "new reduction device"), and to evaluate its effectiveness. Methods: According to the mechanism of thoracolumbar fractures and biomechanics characteristic of reduction, a new reduction device was designed and used in a combination with long U-shaped hollow pedicle screw system. Between January 2014 and January 2016, 36 patients (group A) with single segment thoracolumbar fracture without neurological complications underwent percutaneous pedicle screw fixation, and the clinical data were compared with those of another 39 patients (group B) with thoracolumbar fracture underwent traditional open pedicle screw fixation. There was no significant difference in gender, age, cause of injury, classification of fractures, segments of fractures, injury to operation interval, height percentage of injury vertebrae, and kyphotic angle between 2 groups ( P>0.05). The 2 groups were compared in terms of operation time, length of incision, intraoperative blood loss, drainage volume, visual analogue scale (VAS) at postoperative 24 hours, fluoroscopy frequency, ambulation time, height percentage of injury vertebrae, kyphotic angle and correction. Results: Group A was significantly better than group B in the operation time, length of incision, intraoperative blood loss, drainage volume, VAS score at postoperative 24 hours, and ambulation time ( P<0.05). However, fluoroscopy frequency of group B was significantly less than that of group A ( P<0.05). All patients were followed up 11.2 months on average (range, 7-15 months). There was no intraoperative and postoperative complications of iatrogenic nerve injury, infection, breakage of internal fixation. Mild pulling-out of pedicle screws occurred in 1 case of group A during operation. The kyphotic angle and height percentage of the fractured vertebral body were significantly improved at 3 days after operation when compared with preoperative ones ( P<0.05), but no significant difference was found between 2 groups at 3 days after operation ( P>0.05). Conclusion: Minimally invasive extracorporeal reduction device for percutaneous pedicle screw fixation is an effective and safe treatment of thoracic vertebrae and lumbar vertebrae fractures, because of little trauma, less bleeding, and quicker recovery. PMID- 29798633 TI - [Transfection of lentivirus-bone morphogenetic protein 2 and lentivirus-inhibitor of differentiation 1 into nucleus pulposus for delaying intervertebral disc degeneration in an in vivo rabbit model]. AB - Objective: To investigate if the course of intervertebral disc degeneration (IDD) is delayed by injecting lentivirus (Lv) vector carrying bone morphogenetic protein 2 (BMP-2) and inhibitor of differentiation 1 (Id1) genes directly into the nucleus pulposus. Methods: Thirty-two New Zealand white rabbits, 2.0-2.5 kg in weight and 4 months in age, were used to establish the IDD models at L 3, 4, L 4, 5, and L 5, 6 discs with annular puncture via transabdominal approach. Thirty rabbits with successful modeling were randomly divided into 5 groups, 6 rabbits every group. At 4 weeks after modeling, rabbits were injected with Lv-BMP-2 (group A), with Lv-BMP-2 and Lv-Id1 (group B), with Lv-Id1 (group C), with Lv green fluorescent protein (group D), and with PBS (group E). At 2, 4, and 8 weeks after injection, T2-mapping MRI was performed on 2 rabbits each group to obtain the T2 values, and then subsequently the lumbar disc tissues were harvested to test the mRNA expressions and contents of collagen type II and proteoglycan by real-time fluorescent quantitative PCR and ELISA methods. Results: T2-mapping MRI demonstrated that there was no significant difference in the T2 value between different groups at immediate and 2 weeks after injection ( P>0.05). The T2 value of groups A and B was significantly higher than that of groups C, D, and E at 4 weeks after injection ( P<0.05), but no significant difference was observed between group A and group B ( P>0.05). The T2 value of group B was significantly higher than that of the other groups at 8 weeks after injection ( P<0.05). The real-time fluorescent quantitative PCR and ELISA showed that the expressions and contents of collagen type II and proteoglycan in group B were significantly higher than those in the other groups at 2, 4, and 8 weeks after injection ( P<0.05). Conclusion: Combined application of Lv-BMP-2 and Lv-Id1 can delay IDD changes in rabbit IDD models. PMID- 29798634 TI - [Changes of endogenous Spastin expression after sciatic nerve injury in rats]. AB - Objective: To investigate the expression change of endogenous Spastin after sciatic nerve injury in rats, and to discuss the role and significance in the peripheral nerve regeneration. Methods: Thirty-six adult male Sprague Dawley rats weighing 180-220 g were randomly divided into the experimental group ( n=30) and the control group ( n=6). Sciatic nerve compression damage model was established in the experimental group, and the sciatic nerve was only exposed in the control group. The L 4-6 spinal cord tissue was obtained to detect Spastin mRNA and protein levels by real-time fluorescence quantitative PCR and Western blot at 1, 3, 7, 14, and 28 days after operation in the experimental group ( n=6) and at 7 days in the control group. Meanwhile, the sciatic nerve at 5 mm distal to the injured site was obtained to observe the ultrastructure of the distal axon by transmission electron microscope (TEM). Results: The expression trends of Spastin gene and Spastin protein in L 4-6 spinal cord tissue of 2 groups were basically identical. In the experimental group, the expressions of Spastin gene and protein decreased at the beginning, and then increased; the expressions reduced to the minimum at 7 days after operation, and came back to the initial level at 28 days. The expression levels of Spastin mRNA and protein at 3, 7, and 14 days were significantly lower in the experimental group than the control group ( P<0.05), but no significant difference was noted between 2 groups at 1 and 28 days ( P>0.05). The expression levels of Spastin mRNA and protein at 3, 7, and 14 days were significantly lower than those at 1 and 28 days in the experimental group ( P<0.05), but no significant difference was noted between at 1 day and 28 days ( P>0.05). At 1, 3, and 7 days after operation, the myelin damage was observed by TEM; at 14 days, there were regenerating Schwann cells; at 28 days, a large number of myelinated nerve fibers were seen, which were closed to normal form. Conclusion: In the process of sciatic nerve regeneration after injury, a complex succession of changes take place in the expression of endogenous Spastin protein in rats, indicating that Spastin protein plays an important role in the process. PMID- 29798635 TI - [Effect of cyclic stretch on expression of c-fos gene in rat Achilles-derived tendon stem cells]. AB - Objective: To investigate whether mechanical stretch stimulation affects the expression of the immediate early gene c-fos mRNA in rat Achilles-derived tendon stem cells (TSCs) in vitro. Methods: TSCs were isolated from the Achilles tendons of 8 weeks old male Sprague Dawley rats by enzymatic digestion method and cultured for 3 passages. The TSCs were stimulated by a uniaxial cyclic stretching loading system under the condition of 1 Hz, respectively with 4% or 8% stretch intensity for 0, 5, 15, 30, 60, and 120 minutes. At each time point, TSCs were collected to detect c-fos mRNA expressions and to find the best time-point T max by real-time fluorescence quantitative PCR. Then, TSCs were simulated with 2%, 4%, 6%, 8%, or 12% stretch intensity for T max to observe the relative expressions of c-fos mRNA under different stretch intensities. Next, TSCs were stretched for 0, 5, or 15 minutes respectively and followed by incubation at relax status up to T max to observe the changes of c-fos mRNA expressions after short period stimulation. Finally, TSCs were stimulated with 4% or 8% stretch intensity respectively for 0, T max, or 120 minutes to detect the expressions of the tenogenic differentiation related genes [collagen type I, tenomodulin (TNMD)], the osteogenic differentiation related genes [runt related transcription factor 2 (Runx2), distal-less homeobox 5 (Dlx5)], and the adipogenic differentiation related gene [fatty acid binding protein 4 (FABP4)]. Results: Under 4% or 8% stretch intensity, the relative expressions of c-fos mRNA significantly increased at 15 minutes ( P<0.05), reached the maximum at 30 minutes ( P<0.05), and returned to baseline at 60 minutes ( P>0.05) when compared with expression at 0 minute. Therefore, T max was 30 minutes. The stretch intensity of 2% was enough to cause the expression of c-fos mRNA at 30 minutes, and the expression was significantly higher under the stretch intensity of 6%, 8%, and 12% than 2% and 4% ( P<0.05). Even for a short period stimulation of 5 minutes, c-fos mRNA expression could still significantly increase at 30 minutes ( P<0.05). The relative expressions of differentiation related genes at 30 and 120 minutes showed no significant difference when compared with the expression at 0 minute under 4% stretch intensity ( P>0.05); but the relative expression of Runx2 gene significantly increased at 30 minutes, and the relative expressions of collagen type I, TNMD, Dlx5, and Runx2 increased at 120 minutes under 8% stretch intensity ( P<0.05). Conclusion: Mechanical stretch stimulation can affect the relative expression of the immediate early gene c-fos mRNA of rat Achilles derived tendon stem cells in vitro, and there is time- and intensity-dependence. It is suggested that the mechanical stimulation with different time or intensity may affect the differentiation of TSCs at early stage. This study is meaningful for the further study on TSCs intracellular mechanical signal transfer mechanism. PMID- 29798636 TI - [Role and mechanism of stromal cell derived factor 1 on proliferation of vascular endothelial cells]. AB - Objective: To investigate the role and relative mechanism of stromal cell derived factorl (SDF-1) secreted by nucleus pulposus cells (NPCs) on the proliferation of vascular endothelial cells (VECs). Methods: The NPCs were isolated from the degenerated disc specimens after discectomy. NPCs at passage 1 were transfected with lentivirus-mediated SDF-1 over-expression; transfected and untransfected NPCs at passage 2 were cultured in the three-dimensional alvetex(r) scaffold, then they were co-cultured with HMEC-1 cells. The morphology of NPCs was observed by scanning electron microscope (SEM), and the apoptosis of HMEC-1 cells was detected by Annexin V/propidiumiodide staining after 72 hours co-culutre. The proliferation of HMEC-1 cells was detected by cell counting kit 8 at 12, 24, 48, and 72 hours in transfected group and untransfected group, respectively. ELISA was used to measure the vascular endothelial growth factor (VEGF) expression level. The virus transfection efficiency and relative Akt pathway were determined by Western blot. Results: The NPCs maintained cell phenotype and secreted much extracellular matrix in three-dimensional-culture by SEM observation. In the co culutre system, after NPCs were transfected with SDF-1 over-expression lentivirus, the proliferation of HMEC-1 cells was significantly increased, while the apoptosis was decreased obviously. The ELISA results demonstrated that the amount of VEGF was remarkably increased in the culture medium. Furthermore, SDF-1 promoted the up-regulation of phosphorylate Akt expression; after inhibition of Akt expression by GSK690693, the proliferation rate of VECs decreased significantly. Conclusion: Over-expression of SDF-1 by NPCs is beneficial for VECs proliferation, which is involved in SDF-1-Akt signalling pathway. PMID- 29798637 TI - [Matrix-induced autologous chondrocyte implantation for treatment of femoral trochlea cartilage injury]. AB - Objective: To determine the short-term effectiveness of matrix-induced autologous chondrocyte implantation (MACI) for femoral trochlea cartilage injury. Methods: A retrospective analysis was performed on the clinical data of 10 patients with femoral trochlea cartilage injury treated with MACI between June 2012 and October 2014. There were 6 males and 4 females, aged from 15 to 48 years (mean, 33 years). The left knee was involved in 3 cases and the right knee in 7 cases. Nine patients had a history of trauma, and 1 case suffered from osteochondritis dissecans. Combined injuries included meniscus injury in 1 case, anterior cruciate ligament injury in 3 cases, and lateral collateral ligament tear in 2 cases. The mean lesion depth was 2.80 mm (range, 2-7 mm), with the mean defect size of 84.85 mm 2 (range, 28.26-153.86 mm 2). The mean duration of definite diagnosis was 14 days (range, 5 days to 3 months). By using arthroscopic biopsy, 200-300 mg healthy articular cartilage at non weight-bearing area of the knee femoral trochlea was collected as a source of seed cells, which were isolated and cultured to prepare MACI membrane. The adhesion activity, growth rate, and mechanical properties of the chondrocytes on the Bio-gide collagen scaffold were evaluated. In addition, the stretch rate, tensile strength, and suture strength of scaffold were tested. MACI membrane was implanted after 2 weeks to 6 months. The visual analogou scale (VAS), Lysholm score, and Tegner movement level score at preoperation and last follow-up were used to assess the function. Results: The MACI membrane was successfully prepared, and the human chondrocytes adhered and grew well on the Bio-gide collagen scaffold. Mechanical test showed that MACI membrane had the stretch rate of 65.27%, the tensile strength of 26.81 MPa, and the suture strength of 6.49 N, indicating good mechanical properties. MACI membrane was successfully implanted. The mean operation time was 58.5 minutes (range, 43-99 minutes), and the mean hospitalization time was 7 days (range, 6-15 days). All incisions healed well. Ten cases were followed up 9 to 16 months (mean, 12 months). Four cases underwent iliac bone graft surgery. The mean healing time was 14 weeks (range, 12-16 weeks). No complications of osteochondrolysis, knee pain, nerve and vascular injury, deep vein thrombosis, and knee adhesion occurred during follow-up. The VAS score, Lysholm score, and Tegner score at last follow-up were significantly improved when compared with preoperative scores ( t=12.060, P=0.000; t=-9.200, P=0.000; t=-14.000, P=0.000). Conclusion: MACI for femoral trochlea cartilage injury has good short-term effectiveness, with less injury and fast function recovery. PMID- 29798638 TI - [Research progress of P75 neurotrophin receptor and new idea of nonunion treatment]. AB - Objective: To review the research progress of P75 neurotrophin receptor (P75NTR) so as to clarify its mechanism, and to explore its relationship with nonunion so as to provide a new idea for the treatment of nonunion. Methods: The related domestic and foreign literature of P75NTR in recent years was extensively reviewed, summarized, and analyzed to find out the mechanism of action of P75NTR and the pathological factors of nonunion formation. Results: P75NTR can express in nonunion tissues and lead to defect of fibrin degradation and inhibition of angiogenesis, which play an important role in the pathogenesis of nonunion. Conclusion: It needs to be confirmed by further study whether the purpose of treating nonunion can be achieved by blocking the effects described above of P75NTR. PMID- 29798639 TI - [Research development of computer assisted navigation and robotics in unicompartmental knee arthroplasty]. AB - Objective: To summarize the computer assisted navigation and robotics in the classification of knee surgery, and the development, surgical indications and contraindication, effectiveness, and the research progress of computer assisted navigation and robotics in unicompartmental knee arthroplasty (UKA). Methods: The related literature on computer assisted navigation and robotics in UKA was extensively reviewed, summarized, and analyzed. Results: Recently, satisfactory results have been achieved in UKA for the treatment of single compartmental knee osteoarthritis. With the rapid development of computer navigation and robotic technology gradually combined with clinical practice, the great precision and accuracy of implant have been improved in computer navigation and robotics in UKA surgery. Postoperative function is well recovered, meanwhile, prosthesis survival can be significantly increased. Conclusion: Computer assisted navigation and robotics in UKA can greatly improve the accuracy of the implant when compared with traditional UKA. The early effectiveness is satisfactory, but the long-term effectiveness still needs to be further observed. PMID- 29798641 TI - [Role of cell autophagy in peripheral nerve injury and regeneration]. AB - Objective: To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. Methods: The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. Results: The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. Conclusion: The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury. PMID- 29798640 TI - [Research progress of microRNA and its non-viral vector in intervertebral disc degeneration]. AB - Objective: To summarize the research progress of microRNA (miRNA) and its non viral vector in intervertebral disc degeneration (IDD) and to investigate the potential of non-viral vector delivery of miRNA in clinical application. Methods: The related literature about the role of miRNA in IDD and its non-viral delivery system was reviewed and analyzed. Results: MiRNA can regulate the related gene expression level and further participate in the pathophysiologic process in degenerated intervertebral disc, miRNA delivered by various non-viral vectors has obtained an ideal effect in some diseases. Conclusion: MiRNA plays a great role in the cellular and molecular mechanisms of IDD, as a safe and effective strategy for gene therapy, non-viral vector provides new possibilities for IDD treated with miRNA. PMID- 29798642 TI - [Effectiveness of acetabular revision using a metal reconstruction cage]. AB - Objective: To explore the clinical outcomes of acetabular revision using a metal reconstruction cage. Methods: Between October 2006 and October 2013, 16 patients (16 hips) underwent acetabular revision with a metal reconstruction cage. There were 4 males and 12 females, with the mean age of 62.7 years (range, 49-78 years). The time from total hip arthroplasty to revision was 3-15 years (mean, 8.2 years). The causes for revision were aseptic acetabular loosening in 15 cases, and femoral periprosthetic fracture (Vancouver type B3) in 1 case. According to the American Academy of Orthopaedic Surgeons (AAOS) classification, there were 12 cases of type III and 4 cases of type IV; according to the Paprosky classification, there were 12 cases of type IIIA and 4 cases of type IIIB. Harris score was used for hip function evaluation, and visual analogue scale (VAS) for pain in the thigh. X-ray films were taken for imaging evaluation. Results: Healing of incision by first intention was obtained in all patients. Deep venous thrombosis occurred in 1 patient, and was cured after anticoagulation therapy. No complications of infection, neurovascular injury, and prosthetic dislocation were found. Sixteen patients were followed up 6.8 years on average (range, 2-9 years). The Harris score was significantly increased from preoperative 42.44+/-4.66 to 91.88+/-3.28 at last follow-up ( t=-106.30, P=0.00). Two patients had mild pain in the thigh, but pain disappeared at 1 year after operation. At immediate after operation, the abduction angle was 37-54 degrees (mean, 42.9 degrees ). The distance between acetabular rotation centre and teardrop line was (33.67+/-12.19) mm for preoperative value and was (20.67+/-9.63) mm for postoperative value, showing significant difference ( t=-9.60, P=0.00). The distance between acetabular rotation centre and lateral teardrop was (34.98+/-12.30) mm for preoperative value and was (40.04+/-6.61) mm for postoperative value, showing significant difference ( t=-3.15, P=0.00). X-ray film results showed bony fusion at the osteotomy sites at 4 to 12 months after operation. No continuous radiolucent line, prosthetic dislocation, or osteolysis was found, and bony ingrowth was observed in all patients. No patient received re-revision due to prosthetic loosening. Conclusion: The metal reconstruction cage for acetabular revision can achieve good effectiveness for patients with serious bone defect. PMID- 29798643 TI - [Effect of acetabular tilt angle on acetabular version in adults with developmental dysplasia of the hip]. AB - Objective: To investigate the difference in acetabular tilt angle (ATA) between adults with deve-lopmental dysplasia of the hip (DDH) and normal adults and the effect of ATA on acetabular version. Methods: Between February 2009 and October 2015, 31 adult female patients with DDH (39 hips) (DDH group) and 31 female patients with osteoarthritis of the knee (31 hips) who had no history of hip disease (control group) were included in this study. The average age was 39 years (range, 18-59 years) in the DDH group, and was 69 years (range, 52-79 years) in control group. The morphometric parameters of the acetabulum including ATA, acetabular anteversion angle (AAA), acetabular inclination angle (AIA), acetabular cranial anteversion angle (ACAA), and acetabular sector angle (ASA) were mea- sured by CT reconstruction; The ASA was used as an index for acetabular coverage of the femoral head. The correlation between ATA and other parameters was analyzed using Pearson correlation analysis. Results: The values of ATA, AAA, and AIA of the DDH group were significantly larger than those of the control group ( P<0.05). The ASA in all directions was significantly decreased in the DDH group when compared with the values in the control group ( P<0.05). There was no significant difference in ACAA between two groups ( t=1.918, P=0.523). The ATA was positively correlated with AAA and ACAA in the DDH group ( r=0.439, P=0.001; r=0.436, P=0.002), but there was no correlation between ATA and AIA ( r=0.123, P=0.308). In the control group, the ATA was not correlated with AAA, ACAA, and AIA ( r=-0.004, P=0.724; r=-0.079, P=0.626; r=-0.058, P=0.724). Regarding acetabular coverage of the femoral head, the ATA and AAA were correlated negatively with anterior ASA ( P<0.05) and positively with posterior ASA ( P<0.05), but had no correlation with superior ASA ( P>0.05) in the DDH group; AIA was correlated negatively with anterior ASA and superior ASA ( P<0.05) and had no correlation with posterior ASA ( r=-0.092, P=0.440). In the control group, there was no correlation between ATA and ASA in any direction ( P>0.05). In the DDH group, defects of the acetabular anterior wall, lateral wall, and posterior wall were observed in 18 hips (46.2%), 15 hips (38.5%), and 6 hips (15.3%), respectively. ATA value of the posterior wall defect [(15.70+/-10.00) degrees ] was significantly smaller than those of the acetabular anterior wall and lateral wall defects [(22.91+/-5.06) degrees and (21.59+/-3.81) degrees ] ( P<0.05), but no signficant difference was found between anterior wall and lateral wall defects ( P>0.05). Conclusion: ATA will influence acetabular version in DDH. The anterior rotation of the acetabular fragment during periacetabular osteotomies is an anatomically reasonable maneuver for hips with anterolateral acetabular defect, while the maneuver should be avoided in hips with posterior acetabular defect. PMID- 29798644 TI - [Efficacy comparison of different methods to treat femoral intertrochanteric fracture in aged patients]. AB - Objective: To compare the efficacy of proximal femoral nail anti-rotation (PFNA), locking compression plate (LCP), and artificial femoral head replacement for femoral intertrochanteric fracture in aged patients so as to provide reference for clinical treatment. Methods: A retrospective analysis was made on the clinical data of 150 aged patients with femoral intertrochanteric fracture treated between September 2009 and March 2016. PFNA was used in 51 cases (group A), LCP in 53 cases (group B), and artificial femoral head replacement in 46 cases (group C). There was no significant difference in sex, age, side, cause of injury, injury to operation time, type of fracture, and combined medical diseases between groups ( P>0.05). The incision length, operation time, intraoperative blood loss, time for full weight bearing, hip Harris score, and complications were recorded and compared between groups. Results: The patients were followed up 12-23 months (mean, 18.6 months) in group A, 12-25 months (mean, 19.0 months) in group B, and 12-24 months (mean, 18.9 months) in group C. The incision length, operation time, and intraoperative blood loss of group A were significantly less than those of groups B and C ( P<0.05); the operation time of group C was significantly shorter than that of group B ( P<0.05), but there was no significant difference in incision length and intraoperative blood loss ( P>0.05). The time for full weight bearing was significantly shorter in group C than groups A and B, and in group A than group B ( P<0.05). Postoperative complications occurred in 11 patients of group A (21.6%), 14 patients of group B (26.4%), and 2 patients of group C (4.3%), showing significant difference between group C and group A or group B ( P<0.05), but no significant difference was found between groups A and B ( P>0.05). Hip Harris score at 12 months after operation had no significant difference between groups ( P>0.05). Conclusion: PFNA, LCP, and artificial femoral head replacement are all effective methods to treat femoral intertrochanteric fracture in aged patients. PFNA has the advantages of small incision, short operation time, less bleeding and simple procedure, and artificial femoral head replacement has the advantages of early time for full weight bearing, less bed rest time, and less complications. For these patients, PFNA and artificial femoral head replacement are appropriate. PMID- 29798645 TI - [Application of improved precision alignment method of lower limbs mechanical alignment on open wedge high tibial osteotomy]. AB - Objective: To evaluate the effects of the improved precision alignment method of lower limbs mecha-nical alignment for osteoarthritis of the knee in open wedge high tibial osteotomy (OWHTO). Methods: A retrospective analysis was made on the clinical data of 62 patients (68 knees) with knee osteoarthritis in the medial compartment treated with OWHTO between January 2012 and December 2015 who accorded with the inclusion criteria. The traditional method for positioning lower limb mechanical force line was used in 29 cases (32 knees) (traditional group), and improved method for positioning lower limb mechanical force line in 33 cases (36 knees) (modified group). There was no significant difference in gender, age, side, course of disease, and osteoarthritis grading between two groups ( P>0.05) with comparable. The operation time, intraoperative fluoroscopy times, and intraoperative blood loss were recorded in two groups; Before and after operation, the lower limb mechanical force line was observed on the X-ray films, which was expressed by hip-knee-ankle angle (HKA). The clinical efficacy was evaluated by the American Hospital for Special Surgery (HSS) score, and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Results: Incision hematoma occurred in 1 case of traditional group and was cured at 3 weeks after symptomatic treatment; and primary healing was obtained in the other patients, with no early complications. The operation time and intraoperative fluoroscopy times of the modified group were significantly lower than those of the traditional group ( t=11.934, P=0.000; t=11.663, P=0.000), but there was no significant difference in blood loss between the two groups ( t=0.209, P=0.835). The patients were followed up for 6 to 24 months (mean, 12.7 months) in the traditional group and for 3 to 22 months (mean, 13.2 months) in the modified group. The medial knee pain disappeared in all patients. At last follow-up, the HSS score and WOMAC score were significantly improved when compared with preoperative scores in two groups ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Postoperative X-ray examination showed that the tibiofemoral angle was corrected in the two groups. The HKA angle at immediate after operation and last follow-up was significantly higher than angle at pre-operation in two groups ( P<0.05), but there was no significant difference between at immediate after operation and at last follow-up ( P>0.05). Conclusion: Compared with the traditional method for positioning lower limb mechanical force line, the improved precision alignment method can reduce the times of intraoperative fluoroscopy and shorten the operation time, which reduces the radiation exposure of both doctors and patients. PMID- 29798646 TI - [Safety evaluation of secondary conversion from external fixation to internal fixation for open tibia fractures]. AB - Objective: To evaluate the safety of conversion from external fixation to internal fixation for open tibia fractures. Methods: Between January 2010 and December 2014, 94 patients (98 limbs) with open tibia fractures were initially treated with external fixators at the first stage, and the clinical data were retrospectively analyzed. In 29 cases (31 limbs), the external fixators were changed to internal fixation for discomfort, pin tract response, Schantz pin loosening, delayed union or non-union after complete wound healing and normal or close to normal levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and the leucocyte count as well as the neutrophil ratio (trial group); in 65 cases (67 limbs), the external fixators were used as the ultimate treatment in the control group. There was no significant difference in gender, age, side of the limbs, interval from injury to the first debridement, initial pathogenic bacteria, the limbs that skin grafting or flap transferring for skin and soft tissue defect between the two groups ( P>0.05). The incidence of Gustilo type III fractures in the control group was significantly higher than that in the trial group ( P=0.000). The overall incidence of infection was calculated respectively in the two groups. The incidence of infection according to different fracture types and whether skin grafting or flap transferring was compared between the two groups. The information of the pathogenic bacteria was recorded in the infected patients, and it was compared with the results of the initial culture. The incidence of infection in the patients of the trial group using different internal fixation instruments was recorded. Results: The overall incidences of infection for the trial and control groups were 9.7% (3/31) and 9.0% (6/67) respectively, showing no significant difference ( chi2=0.013, P=0.909). No infection occurred in Gustilo type I and type II patients. The incidence of infection for Gustilo type IIIA patients in the trial group and the control group were 14.3% (1/7) and 6.3% (2/32) respectively, showing no significant difference ( chi2=0.509, P=0.476); the incidence of infection for type IIIB patients in the two groups were 50.0% (2/4) and 14.3% (2/14) respectively, showing no significant difference ( chi2=2.168, P=0.141); and the incidence of infection for type IIIC patients in the two groups were 0 and 16.7% (2/12) respectively, showing no significant difference ( chi2=0.361, P=0.548). Of all the infected limbs, only 1 limb in the trial group had the same Staphylococcus Aureus as the result of the initial culture. In the patients who underwent skin grafting or flap transferring, the incidence of infection in the trial and control groups were 33.3% (2/6) and 13.3% (2/15) respectively, showing no significant difference ( chi2=1.059, P=0.303). After conversion to internal fixation, no infection occurred in the cases that fixed with nails (11 limbs), and infection occurred in 4 of 20 limbs that fixed with plates, with an incidence of infection of 20%. Conclusion: Conversion from external fixation to internal fixation for open tibia fractures is safe in most cases. However, for open tibia fractures with extensive and severe soft tissue injury, especially Gustilo type III patients who achieved wound heal after flap transfer or skin grafting, the choice of secondary conversion to internal fixation should carried out cautiously. Careful pre-operative evaluation of soft tissue status, cautious choice of fixation instrument and meticulous intra-operative soft tissue protection are essential for its safety. PMID- 29798647 TI - [Comparative study on treatment of thoracolumbar burst fractures with bone grafting by transpedicular approach and by interlaminal small fenestration]. AB - Objective: To investigate the effectiveness and long-term stability of small fenestration vertebral bone grafting and transpedicular bone grafting in the treatment of Denis types A and B thoracolumbar burst fractures. Methods: Between January 2012 and February 2014, 50 patients with Denis type A or B thoracolumbar burst fractures were treated with vertebroplasty and pedicle screw rod fixation system, and the clinical data were retrospectively analyzed. Small fenestration vertebral bone grafting by trans-interlaminar approach was used in 30 cases (group A), and bone grafting by unilateral transpedicular approach was used in 20 cases (group B). X-ray and CT examinations of the thoracolumbar vertebrae were performed routinely before and after operation. There was no significant difference in sex, age, cause of injury, time from injury to operation, fracture type, injury segment, and preoperative Frankel classification, the percentage of the anterior body height of the injured vertebra, and visual analogue scale (VAS) score between two groups ( P>0.05). There was significant difference in preoperative Cobb angle of kyphosis between two groups ( P<0.05). The Cobb angle of kyphosis, the percentage of the anterior body height of the injured vertebra, and the recovery of neurological function were recorded and compared between two groups. Results: The patients were followed up for 16-31 months (mean, 19.1 months) in group A and for 17-25 months (mean, 20.2 months) in group B. Primary healing of incisions was obtained in the two groups; no nerve injury and other operative complications occurred. The neurological function was improved in varying degrees in the other patients with neurological impairment before operation except patients at grade A of Frankel classification. The lumbar back pain was relieved in two groups. There was significant difference in VAS score between before operation and at 3 months after operation or last follow-up in two groups ( P<0.05), but no significant difference was found between at 3 months and last follow-up in two groups and between two groups at each time point after operation ( P>0.05). X-ray examination showed that there was no breakage of nail and bar, or dislocation and loosening of internal fixation during follow-up period. The bone grafts filled well and fused in the fractured vertebra. The vertebral height recovered well after operation. The percentage of the anterior body height of the in-jured vertebra and Cobb angle of kyphosis at 1 week, 3 months, and last follow-up were significantly better than preope-rative ones in two groups ( P<0.05), but there was no significant difference between different time points after operation ( P>0.05), and between two groups at each time point after operation ( P>0.05). Conclusion: For Denis types A and B thoracolumbar burst fractures, vertebral bone grafting and pedicle screw internal fixation through interlaminal small fene-stration or transpedicular approach can restore the vertebral height, correct kyphosis, and maintain the vertebral stability, which reduce the risk of complications of loosening and breakage of internal fixators. The appropriate bone grafting approach can be chosen based on the degree of spinal canal space occupying, collapse of vertebral and spinal cord injury. PMID- 29798648 TI - [Common pedicle screw placement under direct vision combined with dome shaped decompression via small incision for double segment thoracolumbar fracture with nerve injury]. AB - Objective: To determine the feasibility, safety, and efficacy of common pedicle screw placement under direct vision combined with dome shaped decompression via small incision for double segment thoracolumbar fracture with nerve injury. Methods: A retrospective analysis was performed on the clinical data of 32 patients with double segment thoracolumbar fracture with nerve injury undergoing common pedicle screw placement under direct vision combined with dome shaped decompression via small incision between November 2011 and November 2015 (combined surgery group), and another 32 patients undergoing traditional open pedicle screw fixation surgery (traditional surgery group). There was no significant difference in gender, age, cause of injury, time of injury-to surgery, injury segments and Frankel classification of neurological function between two groups ( P>0.05). The length of soft tissue dissection, the operative time, the blood loss during surgery, the postoperative drainage, the visual analogue scale (VAS) of incision after surgery, and recovery of neurological function after surgery were evaluated. Results: All cases were followed up 9 to 12 months (mean, 10.5 months) in combined surgery group, and 8 to 12 months (mean, 9.8 months) in traditional surgery group. The length of soft tissue dissection, the operative time, the blood loss during surgery, the postoperative drainage, and the postoperative VAS score in the combined surgery group were significantly better than those in the traditional surgery group ( P<0.05). Dural rupture during surgery and pedicle screw pulling-out at 6 months after surgery occurred in 2 cases and 1 case of the combined surgery group; dural rupture during surgery occurred in 1 case of the traditional surgery group. The X-ray films showed good decompression, and fracture healing; A certain degree of neurological function recovery was achieved in two groups. Conclusion: Common pedicle screw placement under direct vision combined with dome shaped decompression via small incision can significantly reduce iatrogenic trauma and provide good nerve decompression. Therefore, it is a safe, effective, and minimally invasive treatment method for double segment thoracolumbar fracture with neurological injury. PMID- 29798649 TI - [Application of ultrasonic bone curette in posterior cervical single open-door laminoplasty]. AB - Objective: To investigate the safety and reliability of ultrasonic bone curette in posterior cervical single open-door laminoplasty. Methods: The clinical data were retrospectively analyzed, from 193 patients who underwent single open-door laminoplasty (C 3-7) from January 2012 to January 2016. The patients were divided into three groups according to different instruments: posterior single open-door laminoplasty was performed with ultrasonic bone curette in 61 cases (group A), with bite forceps in 73 cases (group B), and with micro-grinding drill in 59 cases (group C). There was no significant difference in gender, age, the course of disease, underlying disease and preoperative Japanese Orthopedic Association (JOA) score, visual analogue scale (VAS) between groups ( P>0.05). The operative time, intraoperative blood loss, drainage volume at 48 hours, JOA score, improvement rate, VAS and perioperative com-plication were compared. Results: The operative time, intraoperative blood loss, and drainage volume at 48 hours of group A were significantly less than those in groups B and C ( P<0.05), but there was no significant between groups B and C ( P>0.05). The follow-up time was 12-21 months (mean, 14.6 months) in group A, 24-36 months (mean, 27.5 months) in group B, and 28-47 months (mean, 38.1 months) in group C. There were no cerebrospinal fluid leakage and incision infection in three groups. No complications of internal fixation loosening and rupture occurred during the follow-up. Rediating pain occurred in 6 cases of group A, 8 cases of group B, and 6 cases of group C, and was cured at 1 week after dehydration and physical therapy. No nerve root palsy was found in three groups. Fracture of portal axis occurred in 5 cases (7 segments) of group B and was fixed by micro titanium plate. The JOA score and VAS score at last follow-up were significantly improved when compared with preoperative scores in three groups ( P<0.05); there was no significant difference in JOA score and improvement rate and VAS score between groups ( P>0.05). Conclusion: It is safe and reliable to use the ultrasonic bone curette in posterior cervical single open-door laminoplasty. It can shorten the operative time and has similar clinical curative effect to the traditional operation, and the lateral rotation of the lamina can be avoided. PMID- 29798650 TI - [Effectiveness of percutaneous endoscopic technique in treatment of intraspinal cement leakage after percutaneous vertebroplasty]. AB - Objective: To evaluate the feasibility and safety of percutaneous endoscopic technique in the treatment of intraspinal cement leakage after percutaneous vertebroplasty (PVP). Methods: Between May 2014 and March 2016, 5 patients with lower limb pain and spinal cord injury caused by intraspinal cement leakage after PVP, were treated with percutaneous endoscopic spinal decompression. Of 5 cases, 3 were male and 2 were female, aged from 65 to 83 years (mean, 74.4 years). The course of disease was 10-30 days (mean, 16.2 days). Imageological examinations confirmed the levels of cement leakage at T 12, L 1 in 3 cases, and at L 1, 2 in 2 cases; bilateral sides were involved in 1 case and unilateral side in 4 cases. Two patients had lower limb pain, whose visual analogue scale (VAS) were 8 and 7; 3 patients had lower extremities weakness, whose Japanese Orthopedic Association (JOA) 29 scores were 18, 20, and 19. According to American Spinal Injury Association (ASIA) impairment scale, neural function was rated as grade E in 2 cases and grade D in 3 cases. Results: The operation time was 55-119 minutes (mean, 85.6 minutes), and the blood loss was 30-80 mL (mean, 48 mL). CT scan and three-dimensional (3D) reconstruction at 1 day after operation showed that cement leakage was removed in all patients. Five cases were followed up 6-21 months (mean, 12 months). In 2 patients with lower limb pain, and VAS score was significantly decreased to 2 at last follow-up. In 3 patients with lower extremities weakness, the muscle strength was improved progressively, and the JOA29 scores at last follow-up were 21, 23, and 22. Conclusion: Percutaneous endoscopic technique for intraspinal cement leakage after PVP is safe, effective, and feasible. PMID- 29798651 TI - [Clinical application of various forms of free profunda femoral artery pedicled chimeric myocutaneous perforator flap in defect reconstruction after tongue carcinoma resection]. AB - Objective: To investigate the clinical anatomy and application of free profunda femoral artery pedicled chimeric myocutaneous perforator flap in the defect reconstruction after radical resection of tongue carcinoma. Methods: Between April 2011 and January 2016, 44 cases of tongue carcinoma underwent radical resection, and tongue defects were reconstructed by free profunda femoral artery pedicled chimeric myocutaneous perforator flaps at the same stage. There were 40 males and 4 females, with a mean age of 46.3 years (range, 32-71 years). The pathologic type was squamous cell carcinoma, which involved the lingual margin in 24 cases, the ventral tongue in 17 cases, and the mouth floor in 3 cases. According to Union for International Cancer Control (UICC) TNM staging, 16 cases were rated as T 4N 0M 0, 11 cases as T 4N 1M 0, 9 cases as T 3N 1M 0, and 8 cases as T 3N 2M 0. The course of disease ranged from 1 to 22 months (mean, 8.6 months). The size of perforator flap ranged from 8.5 cm*4.0 cm to 12.0 cm*6.5 cm, and the size of muscle flap ranged from 4.0 cm*3.0 cm to 7.5 cm*5.0 cm. The adductor magnus myocutaneous flap with a pedicle of (8.3+/-0.5) cm was used in 11 cases, and the gracilis muscle myocutaneous flap with a pedicle of (8.1+/-0.8) cm was used in 33 cases. The donor sites were sutured directly. Results: All 44 perforator flaps survived uneventfully, and the donor site healed well. The patients were followed up for 12 to 40 months (mean, 23.8 months). The reconstructed tongue had good appearance and function in swallowing and language. No local recurrence was found. Only linear scar was left at the donor sites. Conclusion: The free profunda femoral artery pedicled chimeric myocutaneous perforator flap can be harvested in various forms, and is an ideal choice to reconstruct defect after radical resection of tongue carcinoma. PMID- 29798652 TI - [Reconstruction of oral and maxillofacial soft tissue defects with anterolateral thigh (myocutaneous) flap assisted by computed tomography angiography]. AB - Objective: To investigate the efficacy of anterolateral thigh (myocutaneous) flap designed with computed tomography angiography (CTA) to reconstruct oral and maxillofacial soft tissue defects. Methods: Between January 2011 and December 2015, 23 cases of oral and maxillofacial tumors were treated. There were 14 males and 9 females with the age range from 45 to 72 years (mean, 56.8 years). There were 12 cases of tongue carcinoma, 5 cases of buccal mucosa carcinoma, 4 cases of mouth floor carcinoma, and 2 cases of oropharynx carcinoma; all were squamous cell carcinoma. According to standard TNM staging of the Union for International Cancer Control (UICC), 8 cases were rated as T 2N 0M 0, 3 cases as T 2N 1M 0, 1 case as T 2N 2M 0, 4 cases as T 3N 0M 0, 2 cases as T 3N 1M 0, 2 cases as T 3N 2M 0, 2 cases as T 4N 1M 0, and 1 case as T 4N 2M 0. The course of disease was 1-6 months (mean, 2.4 months). CTA was performed before operation to locate the perforator vessel and its surface projection of emerging point and to design anterolateral thigh (myocutaneous) flap by computer. The defects of soft tissue ranged from 6 cm*4 cm to 11 cm*7 cm after resection of tumor. The flap was used to repair defects, including 14 thinned anterolateral thigh flaps, 7 anterolateral thigh myocutaneous flaps, and 2 anterolateral bilobed flaps; and the flap area ranged from 7 cm* 5 cm to 12 cm*8 cm. The donor sites were sutured directly. Results: CTA showed that myocutaneous perforators penetrated at the fascias of the vastus lateralis muscles in 22 cases with a location rate of 95.7% (22/23). Submandibular fistula occurred in 1 case at 5 days after operation and fistula healed after changed dressings. Other wounds at recipient site and donor site healed at primary stage. Anastomose with 2 vein was performed because of poor venous return in 1 case, and the flap survived. The other flaps survived well. All the patients were followed up 6-36 months (mean, 16.4 months). At 3 months after operation, the simplified recovery standard of speech function and swallow function was established according to the University of Washington Quality of Life Scale (UW-QOL). The speech and swallow function recovered satisfactorily in 22 cases, and not very satisfactorily in 1 case of well differentiated squamous cell carcinoma of the right mouth floor (T 4N 1M 0). No obvious tissue atrophy was observed in 23 cases. No dysfunction was found at the donor site. There was no tumor recurrence in 21 patients; 1 patient accepted the second operation due to lymphonodi metastasis of contralateral neck at 6 months after first operation, who died after 23 months; 1 patient died of distant metastasis at 10 months after first operation. Conclusion: The anterolateral thigh (myocutaneous) flap designed with CTA could well recover the morphology and function of the recipient site. PMID- 29798653 TI - [Efficacy evaluation of sural nerve bridging transplantation for restoration of penis disturbance of sensation after selective dorsal nerve neurotomy]. AB - Objective: To evaluate the clinical effect of sural nerve bridging transplantation for the restoration of penis disturbance of sensation after selective dorsal nerve neurotomy. Methods: Between May 2014 and May 2016, 23 patients underwent sural nerve bridging transplantation for the restoration of penis disturbance of sensation after selective dorsal nerve neurotomy. The age ranged from 19 to 38 years (mean, 27 years). The course of disease was 1-28 months (mean, 14 months). The defect length was 1.0-1.5 cm. Preoperative main neurological sign was sensory disturbance. The chief complaint of 21 patients was a erectile dysfunction; all had normal hormone levels, and there was no other organic diseases or surgical contraindication. According to the self-assessment lists of symptom-SCL90 evaluation, 19 cases had depression, 16 cases had anxiety, and 15 cases had both anxiety and depression; 3 cases had psychological abnormalities (social barriers, etc.). According to the functional neurological evaluation standard of British Medical Research Institute, the static two-point discrimination and sensation recovery standard rating were evaluated before and after operation; sexual pleasure obstacle sensitivity, temperature sense, and other subjective improvement were recorded. The International Index of Erectile Function 5 (IIEF-5) was used to evaluate questionnaire of the patient with erectile dysfunction before and after operation. The psychological state was accessed with the self-assessment lists of symptom-SCL90 evaluation after operation. Results: All incisions healed by first intention. The mean follow-up time was 8 months (range, 6-12 months). Sexual pleasure obstacle was obviously improved in 11 cases, partially improved in 5 cases; the improvements in temperature and tactile sensitivity were achieved in 21 cases; no obvious improvement was observed in 1 case. The sensation recovery standard rating, static two-point discrimination and grade of IIEF-5 were significantly improved at 3 and 6 months after operation when compared with preoperative ones ( P<0.05). At 6 months after operation, symptom was improved in 14 of 19 patients with depression (73.68%), in 12 of 16 patients with anxiety (75.00%), and in 12 of 15 patients with anxiety and depression(80.00%). Conclusion: Sural nerve bridging transplantation is an effective method for the restoration of penis disturbance of sensation after selective dorsal nerve neurotomy. PMID- 29798654 TI - [Comparison of wide local excision and radical excision for Paget's disease involving the penis and scrotum]. AB - Objective: To evaluate the effectiveness and advantages of the wide local excision for Paget's disease involing the penis and scrotum by comparing with the radical excision. Methods: A retrospective analysis was made on the clinical data of 41 patients with Paget's disease involving penis and scrotum who met the inclusion criteria between November 2010 and August 2015. Among them, 14 patients received wide local excision (group A), and 27 patients received radical excision (group B). No significant difference was found in age, course of disease, and lesion site between two groups ( P>0.05). The recurrence rate, operative time, times of intraoperative frozen section pathology, hospitalization time, grade of wound healing, appearance and functions satisfaction were recorded and compared between two groups. Results: The operative time and hospitalization time in group A were significantly shorter than those in group B ( P<0.05); the times of intraoperative frozen section pathology in group A were significantly less than that in group B ( P<0.05). All patients were followed up 13 to 67 months (mean, 35.5 months) in group A and 11 to 70 months (mean, 38.8 months) in group B. Grades A, B, and C wound healing was obtained in 11 cases, 2 cases, and 1 case of group A and in 12 cases, 7 cases, and 8 cases of group B respectively, showing significant difference between two groups ( Z=-2.102, P=0.036). The 5-year recurrence rate was 28.6% (4/14) in group A and 22.2% (6/27) in group B, showing no significant difference ( chi2=0.202, P=0.654). The score of satisfaction in appearance and functions in group A was significantly higher than that in group B ( t=-2.810, P=0.008). Conclusion: Paget's disease involving penis and scrotum has a slow disease progression and good prognosis. Wide local excision can relieve symptoms effectively and obviously decrease perioperative risk in elderly patients, with no significant increase of the recurrence rate. PMID- 29798655 TI - [Effects of rapamycin and deferoxamin on wound healing after ischemia and hypoxia]. AB - Objective: To explore the effect and mechanism of rapamycin and deferoxamin on wound healing after ischemia and hypoxia. Methods: The model of ischemia and hypoxia wound was made on the back of 40 SPF male adult Sprague Dawley rats, weight (300+/-20) g; they were randomly divided into 4 groups ( n=10): the control group (group A), deferoxamine intervention group (group B), rapamycin intervention group (group C), and deferoxamine+rapamycin intervention group (group D). At 3, 6, and 9 days after model preparation, rats of groups A, B, C, and D were intra-peritoneally injected with normal saline, deferoxamin (10 mg/kg), rapamycin (3 mg/kg), deferoxamin (10 mg/kg)+rapamycin (3 mg/kg) respectively. The wound healing was observed and the healing time was recorded in each group; the wound healing tissue was harvested to test the mRNA and protein expressions of mammalian target of rapamycin (mTOR), hypoxia inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) by real-time fluorescence quantitative PCR and Western blot at 2 days after wound healing. Results: All rats survived to the end of the experiment, and wounds healed; the healing time of groups A, B, and D was significantly shorter than that of group C ( P<0.05), but there was no significant difference between groups A, B, and D ( P>0.05). Real-time fluorescence quantitative PCR showed that the expression of mTOR mRNA in groups C and D was significantly decreased when compared with the expressions in groups A and B ( P<0.05); there was significant difference between groups A and B ( P<0.05), but no significant difference between groups C and D ( P>0.05). The expressions of HIF-1alpha mRNA and VEGF mRNA were signi-ficantly higher in groups B and D than groups A and C, and in group A than group C ( P<0.05), but there was no signifi-cant difference between groups B and D ( P>0.05). Western blot showed that the relative expressions of mTOR protein in groups C and D were significantly decreased when compared with the expressions in groups A and B ( P<0.05), but there was no significant difference between groups C and D ( P>0.05). The relative expressions of HIF-1alpha protein in groups A, B, and C were significantly increased when compared with expression in group D ( P<0.05), but there was no significant difference between groups A, B, and C ( P>0.05). The relative expression of VEGF protein were significantly lower in groups B, C, and D than group A, in group D than groups B and C, and in group C than group B ( P<0.05). Conclusion: Defe-roxamin can promote the wound healing of rats after ischemia and hypoxia, and the effect of rapamycin is opposite. It may be related to the existence of mTOR and HIF-1 signaling pathway in chronic ischemia-hypoxia wound. PMID- 29798656 TI - [Preparation of acellular matrix from antler cartilage and its biological compatibility]. AB - Objective: To study the feasibility of acellular matrix materials prepared from deer antler cartilage and its biological compatibility so as to search for a new member of the extracellular matrix family for cartilage regeneration. Methods: The deer antler mesenchymal (M) layer tissue was harvested and treated through decellular process to prepare M layer acellular matrix; histologic observation and detection of M layer acellular matrix DNA content were carried out. The antler stem cells [antlerogenic periosteum (AP) cells] at 2nd passage were labelled by fluorescent stains and by PKH26. Subsequently, the M layer acellular matrix and the AP cells at 2nd passage were co-cultured for 7 days; then the samples were transplanted into nude mice to study the tissue compatibility of M layer acellular matrix in the living animals. Results: HE and DAPI staining confirmed that the M layer acellular matrix did not contain nucleus; the DNA content of the M layer acellular matrix was (19.367+/-5.254) ng/mg, which was significantly lower than that of the normal M layer tissue [(3 805.500+/-519.119) ng/mg]( t=12.630, P=0.000). In vitro co-culture experiments showed that AP cells could adhere to or even embedded in the M layer acellular matrix. Nude mice transplantation experiments showed that the introduced AP cells could proliferate and induce angiogenesis in the M layer acellular matrix. Conclusion: The deer antler cartilage acellular matrix is successfully prepared. The M layer acellular matrix is suitable for adhesion and proliferation of AP cells in vitro and in vivo, and it has the function of stimulating angiogenesis. This model for deer antler cartilage acellular matrix can be applied in cartilage tissue engineering in the future. PMID- 29798657 TI - [Effect of injectable composites of calcium sulfate and hyaluronate in enhancing osteogenesis]. AB - Objective: To fabricate an injectable composite bone substitute with hyaluronic acid (HA) and calcium sulfate and to evaluate the biocompatibility and effect of the composite on cell proliferation, osteogenic differentiation in vitro and osteogenic capability in vivo. Methods: Calcium sulfate powder was mixed with HA solution, cross-linked HA solution, and phosphate buffer solution (PBS) in a ratio of 2?1 ( W/ V) to get composites of CA+HA, CA+HAC, and CA. The standard extracts from above 3 materials were prepared according to ISO10993-5, and were used to culture mouse MC3T3-E1 cells. The composite biocompatibility and cell proliferation in different concentrations of extract were tested with cell counting kit-8 (CCK-8). The cells were cultured with standard medium as a control. The optimal concentration was selected for osteogenic differentiation test, and ELISA Kit was used to determine the alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN). The femoral condylar bone defect was made on New Zealand white rabbits and repaired with CA+HA, CA+HAC, and CA. Micro-CT was done to evaluate new bone formation with bone volume/tissue volume (BV/TV) ratio at 6 and 12 weeks. HE staining was used to observe bone formation. Results: CA+HA and CA+HAC were better in injectability and stability in PBS than CA. The biocompatibility test showed that absorbance ( A) value of CA group was significantly lower than that of control group ( P<0.05) at 6, 12, and 24 hours after culture, but no significant difference was found in A values between CA+HA group or CA+HAC group and control group ( P>0.05). The proliferation test showed 25% and 50% extract of all 3 materials had significantly higher A value than control group ( P<0.05). For 75% and 100% extract, only CA+HA group had significantly higher A value than control group ( P<0.05). And 50% extract was selected for osteogenic differentiation test. At 14 and 21 days, ALP, COL-I and OCN concentrations of CA+HA group and CA+HAC group were significantly higher than those of CA group and control group ( P<0.05). Micro-CT results showed higher BV/TV in CA+HA group and CA+HAC group than CA group at 6 and 12 weeks ( P<0.05), but no significant difference was found between CA+HA group and CA+HAC group ( P>0.05). HE staining revealed that a little bone tissue was seen in CA+HA group and CA+HAC group, but there was no bone formation in CA group at 6 weeks; more streak bone tissue in CA+HA group and CA+HAC group than CA group at 12 weeks. Conclusion: Composites prepared with calcium sulfate and HA or with cross-linked HA are stable, injectable, and biocompatible. The materials have excellent effect on proliferation and differentiation of mouse MC3T3-E1 cells. They also show good osteogenic capability in vivo. So it is a potential bone substitutes for bone defective diseases. PMID- 29798658 TI - [Effect of bone morphogenetic protein 2 and dexamethason on proliferation and differentiation of human dental pulp cells in vitro]. AB - Objective: To investigate the effect of bone morphogenetic protein 2 (BMP-2) and dexamethason (DXM) on proliferation and differentiation of human dental pulp cells in vitro. Methods: Primary human dental pulp cells were cultured in vitro by tissue culture method. The 3rd generation cells were used to identify cell phenotype for vimentin and cytokeratin by immunocytochemistry staining. The 3-5 generations of human dental pulp cells were randomly divided into 4 groups: 100 ng/mL BMP-2 (group A), 1*10 -8 mol/L DXM (group B), and both 100 ng/mL BMP-2 and 1*10 -8 mol/L DXM (group C) were added; neither BMP-2 nor DXM was added in group D as control group. The cell growth curve was drawn at 1, 3, 5, and 7 days after culture. The expressions of osteo/dentanogenic genes including alkaline phosphatase (ALP), dentin sialophoshoprotein (DSPP), and dentin matrix protein 1 (DMP-1) were detected by RT-PCR analysis at 5 and 7 days after culture, the ratio between the positive staining area and the total area by ALP staining at 14 days, and absorbance ( A) value at 562 nm by alizarin red staining at 21 days after culture. Results: Human dental pulp cells were successfully isolated and cultured, which were long fusiform and showed a positive reaction for vimentin and a negative reaction for cytokeratin. The growth curve indicated that cells increased with the extending of incubation time, reached a peak at 5 days, then reduced at 7 days to the level at 3 days. At 5 days after culture, the cells were significantly more in groups A, B, and C than group D ( P<0.05), in group C than group A ( P<0.05), and in group A than group B ( P<0.05). RT-PCR analysis showed that the mRNA expressions of ALP, DSPP, and DMP-1 at 5 days were significantly higher in groups A, B, and C than group D ( P<0.05), and in group C than groups A and B ( P<0.05), but no significant difference was found between groups A and B ( P>0.05); the mRNA expression of DSPP in groups A, B, and C was significantly higher than that in group D ( P<0.05), but there was no significant difference in mRNA expressions between other groups at 7 days ( P>0.05). At 14 days, positive staining in varying degrees was observed in each group, especially in group C; the ratio between the positive staining area and the total area was significantly higher in group C than groups A, B, and D ( P<0.05), and in groups A and B than group D ( P<0.05), but there was no significant difference between groups A and B ( P>0.05). At 21 days, there were a variety of mineralized nodules in groups A, B, and C in nonuniformly scattered or clustered distribution, but no mineralized nodules were observed in group D. The A values of mineralized nodules showed significant difference between groups ( P<0.05). Conclusion: BMP-2 may be more effective in promoting proliferation of human dental pulp cells than DXM. Combined application of BMP-2 and DXM can remarkably promote the proliferation and differentiation of human dental pulp cells. PMID- 29798659 TI - [Research progress of adipose-derived stem cells in skin wound healing]. AB - Objective: To review the research progress of adipose-derived stem cells (ADSCs) in skin wound healing. Methods: The recent experiments and clinical studies on the role of ADSCs in skin wound healing were extensively retrieved and analyzed. Additionally, possible mechanisms and novel application strategies were proposed. Results: As confirmed by in vitro and in vivo experiments and clinical studies, ADSCs promote skin wound healing mainly by two mechanisms: differentiation to target cells that participate in skin wound healing and cytokines paracrine to promote proliferation and migration of various cell lines that are mandatory to promote skin wound healing. Moreover, scaffold materials and cell sheet technology may further add to the potency of ADSCs in promoting skin wound healing. Conclusion: Remarkable progress has been made in the application of ADSCs in skin wound healing. Further studies are needed to explore the application methods of ADSCs. PMID- 29798660 TI - [Protective effect of exosome on organs after ischemia-reperfusion injury]. AB - Objective: To investigate the protective effect of the exosome on the organ damage induced by ische-mia-reperfusion (I/R) so as to provide a new way for the treatment of I/R damage. Methods: The literature related to the treatment of I/R damage was reviewed and analyzed. Results: The exosome volume is small and it is present in blood, cerebrospinal fluid, and urine, which has the function to cross the blood-brain barrier, and protect the heart, brain and other organs after I/R damage. Conclusion: Exosome is a new material for the treatment of I/R organ injury, and it is important to understand the protective effect and possible mechanism. PMID- 29798661 TI - [Application and research progress of subtalar distraction bone block arthrodesis in treatment of calcaneus fracture malunion]. AB - Objective: To review the application and research progress of subtalar distraction bone block arth-rodesis in the treatment of calcaneus fracture malunion. Methods: The recent literature concerning the history, surgical technique, postoperative complication, indications, and curative effect of subtalar distraction arthrodesis with bone graft block interposition in the treatment of calcaneus fracture malunion was summarized and analyzed. Results: Subtalar distraction bone block arthrodesis is one of the main ways to treat calcaneus fracture malunion, including a combined surgery with subtalar arthrodesis and realignment surgery for hindfoot deformity using bone block graft. The advantage is on the base of subtalar joint fusion, through one-time retracting subtalar joint, the posterior articular surface of subtalar joint implants bone block can partially restore calcaneal height, thus improving the function of the foot. Compared with other calcaneal malunion treatments, subtalar distraction arthrodesis is effective to correct complications caused by calcaneus fracture malunion, and it can restore the height of talus and calcaneus, correct loss of talocalcaneal angle, and ease pain. Conclusion: Subtalar distraction bone block arthrodesis has made remarkable progress in the treatment of calcaneus fracture malunion, but it has the disadvantages of postoperative nonunion and absorption of bone block, so further study is needed. PMID- 29798662 TI - A Universal GSH-Responsive Nanoplatform for the Delivery of DNA, mRNA, and Cas9/sgRNA Ribonucleoprotein. AB - The long-sought promise of gene therapy for the treatment of human diseases remains unfulfilled, largely hindered by the lack of an efficient and safe delivery vehicle. In this study, we have developed a universal glutathione responsive nanoplatform for the efficient delivery of negatively charged genetic biomacromolecules. The cationic block copolymer, poly(aspartic acid-(2-aminoethyl disulfide)-(4-imidazolecarboxylic acid))-poly(ethylene glycol), bearing imidazole residues and disulfide bonds, can form polyplexes with negatively charged DNA, mRNA, and Cas9/sgRNA ribonucleoprotein (RNP) through electrostatic interactions, which enable efficient cellular uptake, endosomal escape, and cytosol unpacking of the payloads. To facilitate the nuclear transport of DNA and RNP, the nuclear localization signal peptide was integrated into the DNA or RNP polyplexes. All three polyplex systems were fully characterized and optimized in vitro. Their relatively high transfection efficiency and low cytotoxicity, as well as convenient surface functionalization merit further investigation. PMID- 29798663 TI - Overcoming Multidrug Resistance by Codelivery of MDR1-Targeting siRNA and Doxorubicin Using EphA10-Mediated pH-Sensitive Lipoplexes: In Vitro and In Vivo Evaluation. AB - The therapeutic efficacy of chemotherapy is dramatically hindered by multidrug resistance (MDR), which is induced by the overexpression of P-glycoprotein (P gp). The codelivery of an antitumor drug and siRNA is an effective strategy recently applied in overcoming P-gp-related MDR. In this study, a multifunctional drug delivery system with both pH-sensitive feature and active targetability was designed, in which MDR1-siRNA and DOX were successfully loaded. The resulting carrier EphA10 antibody-conjugated pH-sensitive doxorubicin (DOX), MDR1-siRNA coloading lipoplexes (shortened as DOX + siRNA/ePL) with high serum stability had favorable physicochemical properties. DOX + siRNA/ePL exhibited an incremental cellular uptake, enhanced P-gp downregulation efficacy, as well as a better cell cytotoxicity in human breast cancer cell line/adriamycin drug-resistant (MCF 7/ADR) cells. The results of the intracellular colocalization study indicated that DOX + siRNA/ePL possessed the ability for pH-responsive rapid endosomal escape in a time-dependent characteristic. Meanwhile, the in vivo antitumor activities suggested that DOX + siRNA/ePL could prolong the circulation time as well as specifically accumulate in the tumor cells via receptor-mediated endocytosis after intravenous administration into the blood system. The histological study further demonstrated that DOX + siRNA/ePL could inhibit the proliferation, induce apoptosis effect, and downregulate the P-gp expression in vivo. Altogether, DOX + siRNA/ePL was expected to be a suitable codelivery system for overcoming the MDR effect. PMID- 29798664 TI - Synthetic Studies Toward the Skyllamycins: Total Synthesis and Generation of Simplified Analogues. AB - Herein, we report our synthetic studies toward the skyllamycins, a highly modified class of nonribosomal peptide natural products which contain a number of interesting structural features, including the extremely rare alpha-OH-glycine residue. Before embarking on the synthesis of the natural products, we prepared four structurally simpler analogues. Access to both the analogues and the natural products first required the synthesis of a number of nonproteinogenic amino acids, including three beta-OH amino acids that were accessed from the convenient chiral precursor Garner's aldehyde. Following the preparation of the suitably protected nonproteinogenic amino acids, the skyllamycin analogues were assembled using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. To access the natural products (skyllamycins A-C) the synthetic route used for the analogues was modified. Specifically, linear peptide precursors containing a C-terminal amide were synthesized via solid-phase peptide synthesis. After cleavage from the resin the N-terminal serine residue was oxidatively cleaved to a glyoxyamide moiety. The target natural products, skyllamycins A-C, were successfully prepared via a final step cyclization with concomitant formation of the unusual alpha-OH-glycine residue. Purification and spectroscopic comparison to the authentic isolated material confirmed the identity of the synthetic natural products. PMID- 29798666 TI - Redox Activity, Ligand Protonation, and Variable Coordination Modes of Diimino Pyrrole Complexes of Palladium. AB - Ligand-based functionality is a prominent method of increasing the reactivity or stability of metal centers in coordination chemistry. Some of the most successful catalysts use ligand-based redox activity, pendant protons, or hemilability in order to specifically accelerate catalysis. Here we report the diimino-pyrrole ligand Tol,CyDIPyH (Tol,CyDIPy = 2,5-bis( N-cyclohexyl-1-( p tolyl)methanimine)pyrrolide), which exhibits all three of these ligand properties. Metalation of Tol,CyDIPy to Pd gives the pseudo-square planar complex (Tol,CyDIPy)PdCl, which upon reduction forms a mixture of products, including a Pd(I)-Pd(I) dimer wherein Tol,CyDIPy bridges the dimeric unit. Upon addition of PMe3, the imine arms of (Tol,CyDIPy)PdCl are displaced to yield (Tol,CyDIPy)Pd(PMe3)2Cl, where the Tol,CyDIPy ligand binds in a monodentate fashion. This complex can be reduced to generate a ligand-based radical, as shown by EPR spectroscopy. Finally, (Tol,CyDIPy)PdCl also can be protonated at the imine arm, exhibiting a total of three different coordination modes across this series of complexes. Taken together, these studies show that Tol,CyDIPy exhibits notable flexibility in its coordination and redox chemistry. PMID- 29798665 TI - Three Novel Escherichia coli Vectors for Convenient and Efficient Molecular Biological Manipulations. AB - We have constructed novel plasmids pANY2, pANY3, and pANY6 for flexible cloning with low false positives, efficient expression, and convenient purification of proteins. The pANY2 plasmid can be used for efficient isopropyl-beta-d thiogalactoside (IPTG) induced protein expression, while the pANY3 plasmid can be used for temperature-induced expression. The pANY6 plasmid contains a self cleaving elastin-like protein (ELP) tag for purification of recombinant protein by simple ELP-mediated precipitation steps and removal of the ELP tag by self cleavage. A urea-based denaturation and refolding processes for renaturation of insoluble inclusion bodies can be conveniently integrated into the ELP-mediated precipitation protocol, removing time-consuming dialysis steps. These novel vectors, together with the described strategies of gene cloning, protein expression, and purification, may have wide applications in biosciences, agricultural, food technologies, and so forth. PMID- 29798667 TI - Total Synthesis of the Highly N-Methylated Peptide Jahanyne. AB - Total synthesis of jahanyne (1) was achieved from commercially available materials on a 38 mg scale. The Boc- N-Me- L-Val-OH fragment along with the HATU/DIPEA coupling condition was applied to avoid the diketopiperazine side reaction in solution phase synthesis. PMID- 29798668 TI - Mining the Chemical Information on Urban Wastewater: Monitoring Human Exposure to Phosphorus Flame Retardants and Plasticizers. AB - At the individual level, exposure to contaminants is generally assessed through the analysis of specific biomarkers in biological matrices. However, these studies are costly and logistically demanding, limiting their applicability to monitor population-wide exposure over time and space. By focusing on a selection of exposure biomarkers to phosphorus flame retardants and plasticizers (PFRs), this study aims to explore the possibility of using wastewater as a complementary source of information about exposure. Wastewater samples were collected from five cities in Europe and analyzed using a previously established method. Substantial differences in biomarker levels were observed between the investigated catchments, suggesting differences in exposure. Time trends in biomarkers observed between 2013 and 2016 were found to agree with results from human biomonitoring studies and reports about production volumes. Using Monte Carlo simulations, average urinary concentrations were estimated. These were generally higher compared to results from human biomonitoring studies. Various explanations for these differences were formulated (i.e., other excretion routes, external sources and different sampling approaches). Obtained results show that wastewater analysis provides unique information about geographical and temporal differences in exposure, which would be difficult to gather using other monitoring tools. PMID- 29798669 TI - Dynamics and Reactions of Molecular Ru Catalysts at Carbon Nanotube-Water Interfaces. AB - Immobilization of molecular catalysts to electrode surfaces can improve the recyclability and electron transfer rates. The drawback is that most experimental techniques and theoretical methods are not applicable. Here we present results from a study of a ruthenium water oxidation catalyst [RuVO(bda)L2] in explicit water at a carbon nanotube water interface, forming the key O-O bond between two 128 atom catalysts, all fully dynamically. Our methodology is based on a recently developed empirical valence bond (EVB) model. We follow the key steps of the reaction including diffusion of the catalysts at the interface, formation of the prereactive dimer, and the bond formation between the two catalysts. On the basis of the calculated parameters, we compute the turnover frequency (TOF) at the experimental loading, in excellent agreement with the experiments. The key O-O bond formation was significantly retarded at the surface, and limiting components were identified that could be improved by catalyst modification. PMID- 29798670 TI - Surface Functionalized Fluorescent PS Nanobead Based Dual-Distinct Solid State Sensor for Detection of Volatile Organic Compounds. AB - Solid state emitting, distinctly dual vapor sensors with high quantum yield was developed using polystyrene incorporating two fluorophores following a miniemulsion polymerization method. Selective functionalization with carboxy and amine functionality was used to decorate the resulting polystyrene nanobeads having both perylenebisimide (PBI) and oligo ( p-phenylenevinylene) (OPV) fluorophores. These nanobeads with a size of 70-180 nm showed near white emission under UV light. On contact with vapors of specific electron deficient nitroaromatics OPV emission got selectively quenched to show yellow emission from the nanobeads under UV radiation. Exposure to amine vapor quashed PBI emission selectively resulting in blue emission under UV lamp. Such a vast range of color alteration from white to either blue or yellow from the same sensor makes it a true dual analyte sensor with two distinct outputs. Control of surface functionality (-COOH, -NH2, and neutral) on the nanobeads played a pivotal role in boosting the sensing efficiency; introduction of functionality on the surface facilitated analyte-sensor interaction through hydrogen bonding, prompting their fast responsiveness. Real time, potential device based application was demonstrated with free-standing films which was capable of efficient detection with fast analyte exchange from dilute solutions. Recyclability of the film sensor was demonstrated with 8 cycles of reuse. PMID- 29798671 TI - ZnO-Assisted Growth of CH3NH3PbI3- xCl x Film and Efficient Planar Perovskite Solar Cells with a TiO2/ZnO/C60 Electron Transport Trilayer. AB - Appropriate electron transport layers (ETL) are essential in perovskite solar cells (PSCs) with high power conversion efficiency (PCE). Herein, a TiO2/ZnO/C60 trilayer fabricated on a transparent fluorine-doped tin oxide (FTO) glass substrate is used as a compound ETL in planar PSCs. The trilayer shows positive effects on both perovskite synthesis and device performance. The ZnO layer assists growth of CH3NH3PbI3- xCl x ( x ~ 0) annealed at a lower temperature and with a shorter time, which is due to a more rapid and easier decomposition of the intermediate CH3NH3PbCl3 phase in the growth of CH3NH3PbI3- xCl x. All three materials in the trilayer are important for obtaining PSCs with a high PCE. ZnO is critical for enhancing the open circuit voltage by ensuring proper energy alignment with the TiO2 and C60 layers. C60 enhances carrier extraction from the CH3NH3PbI3- xCl x layer. TiO2 eliminates charge recombination at the FTO surface and ensures efficient electron collection. The best-performing PSC based on the TiO2/ZnO/C60 electron transport trilayer features a PCE of 18.63% with a fill factor of 79.12%. These findings help develop an understanding of the effects of ZnO-containing ETLs on perovskite film synthesis and show promise for the future development of high-performance PSCs with compound ETLs. PMID- 29798672 TI - Highly Stretchable and Transparent Thermistor Based on Self-Healing Double Network Hydrogel. AB - An ultrastretchable thermistor that combines intrinsic stretchability, thermal sensitivity, transparency, and self-healing capability is fabricated. It is found the polyacrylamide/carrageenan double network (DN) hydrogel is highly sensitive to temperature and therefore can be exploited as a novel channel material for a thermistor. This thermistor can be stretched from 0 to 330% strain with the sensitivity as high as 2.6%/ degrees C at extreme 200% strain. Noticeably, the mechanical, electrical, and thermal sensing properties of the DN hydrogel can be self-healed, analogous to the self-healing capability of human skin. The large mechanical deformations, such as flexion and twist with large angles, do not affect the thermal sensitivity. Good flexibility enables the thermistor to be attached on nonplanar curvilinear surfaces for practical temperature detection. Remarkably, the thermal sensitivity can be improved by introducing mechanical strain, making the sensitivity programmable. This thermistor with tunable sensitivity is advantageous over traditional rigid thermistors that lack flexibility in adjusting their sensitivity. In addition to superior sensitivity and stretchability compared with traditional thermistors, this DN hydrogel-based thermistor provides additional advantages of good transparency and self-healing ability, enabling it to be potentially integrated in soft robots to grasp real world information for guiding their actions. PMID- 29798674 TI - Palladium-Catalyzed Benzylic Phosphorylation of Diarylmethyl Carbonates. AB - A palladium-catalyzed benzylic substitution of tert-butyl diarylmethyl carbonates with a pinacol-derived H-phosphonate proceeds to deliver the corresponding benzylic phosphorylated products in good yields. Moreover, the asymmetric synthesis is possible via a Pd/( Rp, R'p)-( S)-Mandyphos-catalyzed kinetic resolution-DYKAT (dynamic kinetic asymmetric transformation) sequence, and optically active alpha-chiral diarylmethylphosphonates are obtained with synthetically useful yields and enantiomeric ratios (up to 50% and 92:8 er). PMID- 29798675 TI - Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C-C Bond Cleavage of 2-Arylindoles. AB - A variety of 2-aminobenzonitriles were prepared from 2-arylindoles in good to excellent yields through tert-butylnitrite (TBN)-mediated nitrosation and sequential iron(III)-catalyzed C-C Bond cleavage in a one-pot fashion. The 2 aminobenzonitriles can be used to rapidly synthesize benzoxazinones by intramolecular condensation. The present method features an inexpensive iron(III) catalyst, gram scalable preparations, and novel C-C bond cleavage of indoles. PMID- 29798673 TI - In Situ Vaccination with Cowpea vs Tobacco Mosaic Virus against Melanoma. AB - Cancer immunotherapy approaches have emerged as novel treatment regimens against cancer. A particularly interesting avenue is the concept of in situ vaccination, where immunostimulatory agents are introduced into an identified tumor to overcome local immunosuppression and, if successful, mount systemic antitumor immunity. We had previously shown that nanoparticles from cowpea mosaic virus (CPMV) are highly potent in inducing long-lasting antitumor immunity when used as an in situ vaccine in various tumor mouse models. Here we asked whether the nanoparticles from tobacco mosaic virus (TMV) could also be applied as an in situ vaccine and, if so, whether efficacy or mechanism of immune-activation would be affected by the nanoparticle size (300 * 18 nm native TMV vs 50 * 18 nm short TMV nanorods), shape (nanorods vs spherical TMV, termed SNP), or state of assembly (assembled TMV rod vs free coat protein, CP). Our studies indicate that CPMV, but less so TMV, elicits potent antitumor immunity after intratumoral treatment of dermal melanoma (B16F10 using C57BL/6 mice). TMV and TMVshort slowed tumor growth and increased survival time, however, at significantly lower potency compared to that of CPMV. There were no apparent differences between TMV, TMVshort, or the SNP indicating that the aspect ratio does not necessarily play a role in plant viral in situ vaccines. The free CPs did not elicit an antitumor response or immunostimulation, which may indicate that a multivalent assembly is required to trigger an innate immune recognition and activation. Differential potency of CPMV vs TMV can be explained with differences in immune-activation: data indicate that CPMV stimulates an antitumor response through recruitment of monocytes into the tumor microenvironment (TME), establishing signaling through the IFN-gamma pathway, which also leads to recruitment of tumor-infiltrated neutrophils (TINs) and natural killer (NK) cells. Furthermore, the priming of the innate immune system also mounts an adaptive response with CD4+ and CD8+ T cell recruitment and establishment of effector memory cells. While the TMV treatment also lead to the recruitment of innate immune cells as well as T cells (although to a lesser degree), key differences were noted in cyto/chemokine profiling with TMV inducing a potent immune response early on characterized by strong pro-inflammatory cytokines, primarily IL-6. Together, data indicate that some plant viral nanotechnology platforms are more suitable for application as in situ vaccines than others; understanding the intricate differences and underlying mechanism of immune-activation may set the stage for clinical development of these technologies. PMID- 29798676 TI - Correction to Improvements to Practical Usability of the "Crystalline Sponge" Method for Organic Structure Determination. PMID- 29798677 TI - Photocatalytic Reaction of Potassium Alkyltrifluoroborates and Sulfur Dioxide with Alkenes. AB - A three-component reaction of potassium alkyltrifluoroborates, the sulfur dioxide surrogate of DABCO.(SO2)2, and alkenes under photocatalysis in the presence of visible light is developed. This reaction works efficiently at room temperature with the insertion of sulfur dioxide under mild conditions, affording diverse sulfones in good to excellent yields. The alkyl radical and alkylsulfonyl radical are generated as key intermediates, and a reductive single-electron transfer is involved in the reaction process. PMID- 29798678 TI - A new alkylbenzoquinone from Embelia rowlandii Gilg. (Myrsinaceae). AB - A new alkylbenzoquinone named embeliquinone (1) together with five known compounds, lupeol (2), 3-O-[6'-O-palmitoyl-beta-d-glucosyl]-spinasta-7,22(23) diene (3), quercetin (4), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxy-heneicosanoylamino] heneicosane-1,3,4-triol-8-ene (5), and beta-sitosterol-3-O-beta-d-glucopyranoside (6) were isolated from the MeOH leaf extract of Embelia rowlandii by using repeated open column chromatography techniques. The structure of the new compound was characterized by analyses of 1D- and 2D-NMR, and MS data. Embeliquinone (1) had moderate anti-cell proliferation activity against A549 cell line with the IC50 value of 21.8 MUM. In addition, 1 exhibited weak antibacterial activities against Klebsiella pneumoniae and Staphylococcus aureus with an MIC value of 206.0 MUM in both cases. PMID- 29798680 TI - The role of cognitive function and physical activity in physical decline in older adults across the cognitive spectrum. AB - OBJECTIVES: The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum. METHODS: Physical function was assessed using the Physiological Profile Assessment (PPA) in 593 participants (cognitively normal [CN]: n = 342, mild cognitive impairment [MCI]: n = 77, dementia: n = 174) at baseline and in 490 participants available for reassessment 1-year later. Neuropsychological performance and physical activity (PA) were assessed at baseline. RESULTS: Median baseline PPA scores for CN, MCI and dementia groups were 0.41 (IQR = -0.09-1.02), 0.66 (IQR = -0.06-1.15) and 2.37 (IQR = 0.93-3.78) respectively. All baseline neuropsychological domains and PA were significantly associated with baseline PPA. There were significant interaction terms (Time * Cognitive Group, Global Cognition, Processing Speed, Executive Function and PA) in the models investigating PPA decline. In multivariate analysis the Time * Executive Function and PA interaction terms were significant, indicating that participants with poorer baseline executive function and reduced PA demonstrated greater physical decline when compared to individuals with better executive function and PA respectively. DISCUSSION: Having MCI or dementia is associated with greater physical decline compared to CN older people. Physical inactivity and executive dysfunction were associated with physical decline in this sample, which included participants with MCI and dementia. Both factors influencing physical decline are potentially amenable to interventions e.g. exercise. PMID- 29798681 TI - Madeira moneywort (Sibthorpia peregrina L.) as a new source of verbascoside and its derivatives with potential phyto-pharmaceutical applications. AB - The qualitative and quantitative characterization of Madeira moneywort (Sibthorpia peregrina L.) compounds was investigated for the first time. The antioxidant activity and the effect of the methanolic extract on digestive enzymes activity linked to type-2 diabetes and obesity were also determined by in vitro assays. A total of 56 components were characterized in S. peregrina. Phenylethanoids glycosides (PhEGs) represented the main classes of compounds (95.23 mg g-1 of dry extract), almost all verbascoside and its derivatives (up to 98.85% of the total individual phenolic content). The analysed sample was active against ABTS, DPPH, nitric oxide and superoxide radicals, suggesting a potential beneficial effect against oxidative stress. In addition, the methanolic extract was able to inhibit the catalytic activity of alpha-, beta-glucosidases, alpha amylase and pancreatic lipase. Overall, S. peregrina showed good perspectives to be explored as a rich source of verbascoside and its derivatives for nutraceutical/pharmaceutical products. PMID- 29798683 TI - Development of a qPCR for the detection of infectious laryngotracheitis virus (ILTV) based on the gE gene. AB - 1. Infectious laryngotracheitis is a respiratory disease that affects the poultry industry worldwide. It is common in flocks with high-bird density, causing major economic losses. 2. In this study, a SYBR(r) FAST polymerase chain reaction (PCR) double-strand DNA intercalating agent assay was performed for the detection of infectious laryngotracheitis virus (ILTV) in clinical samples in comparison with a conventional nested-PCR, both based on the glycoprotein E encoding gene. This assay amplified 56 bp and was capable of detecting 19 to 1 copies of virus. 3. In total, 164 clinical samples were obtained from birds with respiratory problems from the period of 2009-2016. In the nested-PCR, there were 45.12% positive samples and 54.88% negative samples, while in the real-time PCR (qPCR), there were 81.1% positive samples and 18.9% negative samples. 4. In conclusion, qPCR from the DNA double-strand intercalating agent SYBR(r) GREEN FAST was useful for the diagnosis of ILTV because it detected samples that were negative in nested PCR. This assay has advantages, such as a shortened processing-time, and no need for post-amplification processing (electrophoresis) with additional reagents, such as MgCl2 and agarose. Hence, qPCR proved to be useful, rapid and low cost for use with clinical samples. PMID- 29798684 TI - Effects of antiarrhythmics and hypokalemia on the rate adaptation of cardiac repolarization. AB - OBJECTIVES: In normal conditions, sudden heart rate acceleration provokes a rapid reduction in ventricular action potential duration (APD). The protracted APD rate adaptation favors early afterdepolarizations and precipitates arrhythmia. Nevertheless, it is uncertain as to whether the rate-dependent changes of ventricular repolarization can be adversely modified by arrhythmogenic drugs (quinidine and procainamide) and hypokalemia, in comparison to the agents with safe therapeutic profile, such as lidocaine. DESIGN: The rate adaptation of QT interval and monophasic APD obtained from the left ventricular (LV) and the right ventricular (RV) epicardium was examined during rapid cardiac pacing applied in isolated, perfused guinea-pig heart preparations. RESULTS: At baseline, an abrupt increase in cardiac activation rate was associated with a substantial reduction of the QT interval and ventricular APD in the first two cardiac cycles, which was followed by a gradual shortening of repolarization over subsequent pacing intervals. The time constants of the fast (taufast) and slow (tauslow) components of the APD dynamics determined from a double exponential fit were longer in RV compared to LV chamber. Quinidine, procainamide, and hypokalemia prolonged ventricular repolarization and delayed the rate adaptation of the QT interval and APD in LV and RV, as evidenced by increased taufast and tauslow values. In contrast, lidocaine had no effect on the dynamic changes of ventricular repolarization upon heart rate acceleration. CONCLUSIONS: The rate adaptation of ventricular repolarization is delayed by arrhythmogenic interventions, such as quinidine, procainamide, and hypokalemia, but not changed by lidocaine, a clinically safe antiarrhythmic agent. PMID- 29798686 TI - Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis. AB - : Obesity is believed to negatively affect male semen quality and is accompanied by dysregulation of free fatty acid (FFA) metabolism in plasma. However, the implication of dysregulated FFA on semen quality and the involvement of Sertoli cells remain unclear. In the present study, we report obesity decreased Sertoli cell viability through dysregulated FFAs. We observed an increased rate of apoptosis in Sertoli cells, accompanied with elevated FFA levels, in the testes of obese mice that were provided a high-fat diet (HFD). Moreover, the levels of reactive oxygen species were elevated. Furthermore, we demonstrated by in vitro assays that saturated palmitic acid (PA), which is the most common saturated FFA in plasma, led to decreased cell viability of TM4 Sertoli cells in a time- and dose-dependent manner. A similar finding was noted in primary mouse Sertoli cells. In contrast to saturated FFA, omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) protected Sertoli cells from PA-induced lipotoxicity at the physiologically relevant levels. These results indicated that the lipotoxicity of saturated fatty acids might be the cause of obesity-induced Sertoli cell apoptosis, which leads to decreased semen quality. In addition, omega-3 PUFAs could be classified as protective FFAs. ABBREVIATIONS: FFA: free fatty acid; HFD: high-fat diet; SD: standard diet; PA: palmitic acid; PUFA: polyunsaturated fatty acid; AI: apoptotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H tetrazolium bromide; ROS: reactive oxygen species; HE: Hematoxylin and eosin; WT1: Wilm Tumor 1; NAFLD: non- alcoholic fatty liver disease; DCFH-DA: 2', 7' dichlorofluorescin diacetate; 36B4: acidic ribosomal phosphoprotein P0; SD: standard deviation; EPA: eicosapentaenoic acid; PI: propidium iodide; DHA: docosahexenoic acid. PMID- 29798688 TI - Thirteen-year trend in the persistence with vitamin K antagonists for venous thromboembolism in the UK: a cohort study. AB - BACKGROUND: Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE) and is associated with significant recurrence and mortality risk. Standard VTE treatment includes at least 3 months anticoagulation. The objective was to describe time trends in the duration of oral anticoagulation in patients initially treated with vitamin K antagonists (VKAs). METHODS: A retrospective cohort study was conducted on patients with first VTE and VKA treatment initiation within 30 days, identified from the UK Clinical Practice Research Datalink from 2001 to 2014. VKA users were followed for the duration of oral anticoagulation which included switching to non-VKA oral anticoagulants. The probability of remaining on anticoagulation treatment (persistence) was estimated using Kaplan-Meier survival functions. RESULTS: A total of 16,018 patients with VTE initiated VKA; 48.2% males, mean age 62.1 years, median VKA treatment duration 6.5 months. The 90-day persistence increased from 75.6% in 2001 to 91.2% in 2013 (p < .0001) and the 180-day persistence from 39.3% in 2001 to 61.1% in 2013 (p < .0001). This time trend was also shown for patients with DVT, PE, provoked VTE, unprovoked VTE, provoked DVT, unprovoked DVT, provoked PE and unprovoked PE. There were no major differences in persistence between patients with provoked and unprovoked VTE, but persistence was lower following DVT than PE (p < .0001). CONCLUSIONS: The increase in persistence was independent of the presentation of the first VTE (provoked or unprovoked), but higher for first PE. Whether the increasing persistence resulted in decreasing risk of recurrent VTE needs to be confirmed. PMID- 29798687 TI - Thrombotic storm in a 4-year-old boy with a thrombus in the right atrium. AB - Thrombotic storm (TS) is a rare disease, especially with thrombus in the heart of pediatric patient. We present a case of a 4-year-old boy, who was diagnosed with TS during his first hospitalization due to lower extremity deep venous thrombosis, pulmonary embolism, and thrombosis of the inferior vena cava, cerebral, left internal jugular, portal, renal, and iliac veins. He was eventually prescribed with rivaroxaban to control thrombosis after 30 days of successive use of low-molecular-weight heparin, unfractionated heparin, and warfarin, which were demonstrating little effect on preventing thrombosis, and the patient was intolerant to argatroban. While his lupus anticoagulant ratio was slightly above the normal range and no other potential causes such as congenital thrombophilia, severe infection, malignancy, and trauma were confirmed, we suspected antiphospholipid antibody syndrome and prescribed glucocorticoid and rituximab to control the disease. After 36 days of admission, ultrasonography showed recanalization of the former thrombus. One month after discharge, a tumor embolus resembling a mass emerged in his right atrium under effective anticoagulant therapy. During his second admission, he underwent surgical thrombectomy, and pathological examination confirmed the mass to be a platelet rich thrombus rather than tumor embolus or infection. Considering the suspected antiphospholipid antibody syndrome as the cause of the TS, we prescribed aspirin combined with rivaroxaban to prevent thrombosis. In this case, surgery and pathology shed light on the type of thrombus that emerged from the inferior vena cava and traveled to the heart, which is the possible potential cause of TS. It also changed our therapeutic strategy to antiplatelet therapy combined with anticoagulant therapy to control the disease. PMID- 29798690 TI - Exercise-based evaluations and interventions for pulmonary hypertension with connective tissue disorders. AB - INTRODUCTION: Exercise intolerance is a common and often significant limitation in pulmonary arterial hypertension (PAH). This intolerance greatly affects the quality of life and function of the individual with PAH, irrespective of its etiology. In PAH associated with connective tissue disorders (PAH-CTD), exercise intolerance is further amplified by the presence of coexisting musculoskeletal manifestations of CTD. The evaluation of exercise capacity and prescription for exercise training therefore becomes a challenge to the clinician. Areas covered: This review highlights factors contributing to exercise intolerance in PAH-CTD, evaluation methods of exercise capacity and an overview on exercise training and a roadmap for future research. Expert commentary: Exercise intolerance is a complex interplay of cardiovascular, pulmonary, and musculoskeletal systems. Data from cardiopulmonary exercise tests have shown predictive abilities for both diagnosis and prognosis. In its absence, the 6-min walk test can be used to provide similar information thereby making the role of exercise testing an invaluable evaluation method in PAH-CTD. Exercise training data in PAH-CTD are still sparse, though, data from PAH studies suggest potential benefit. However, more research is required in this area of testing and training for greater understanding on exercise hemodynamic, phenotypes, and training benefits. PMID- 29798689 TI - Future perspective for potential Helicobacter pylori eradication therapies. AB - Helicobacter pylori infection of the human stomach causes chronic inflammation and forms a major risk factor for the development of peptic ulcer disease and gastric cancer. Current standard eradication therapies use an acid-suppressing drug and two antibiotics, now frequently supplemented with bismuth. Declining eradication efficiencies, off-target effects of lengthy broad-spectrum antibiotic treatments and the desire of a more systematic eradication in asymptomatic H. pylori carriers to suppress gastric cancer incidence spur a search for an effective vaccine and alternative therapeutic options. Here, we review the current progress in the field, with an emphasis on narrow-spectrum or nonantibiotic therapeutics. PMID- 29798691 TI - Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases. AB - INTRODUCTION: The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters, have been known to exert physiological and neurological effects for decades. The recent identification of a trace amine-sensitive G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), and subsequent development of TAAR1-selective small-molecule ligands, has renewed research into the therapeutic possibilities of trace amine signaling. Areas covered: Recent efforts in elucidating the neuropharmacology of TAAR1, particularly in neuropsychiatric and neurodegenerative disease, addiction, and regulation of arousal state, will be discussed. Focused application of TAAR1 mutants, synthetic TAAR1 ligands, and endogenous biomolecules such as 3 iodothyronamine (T1AM) has yielded a basic functional portrait for TAAR1, despite a complex biochemistry and pharmacology. The close functional relationship between TAAR1 and dopaminergic signaling is likely to underlie many of its CNS effects. However, TAAR1's influences on serotonin and glutamate neurotransmission will also be highlighted. Expert opinion: TAAR1 holds great promise as a therapeutic target for mental illness, addiction, and sleep disorders. A combination of preclinical and translationally driven studies has solidified TAAR1 as a key node in the regulation of dopaminergic signaling. Continued focus on the mechanisms underlying TAAR1's regulation of serotonin and glutamate signaling, as well as dopamine, will yield further disease-relevant insights. PMID- 29798692 TI - Recent advances in electrospun for drug delivery purpose. AB - Electrospun, an advanced technology, has been successfully employed for fibre production and offers many merits in novel drug delivery systems (DDSs). In recent years, electrospun has gained significant attention and attraction of the scientists in soaring numbers. This technology is superior to other technologies in fabricating the fibres which range from micrometers to manometers scale. The selection of appropriate polymers, electrospun processes and electrospun parameters play important roles in controlling the drug release while, treating serious illness. Besides, electrospraying process has similar characteristics to the electrospun and is presented briefly here. Further, in vivo and in vitro evaluations of the electrospun nanofibers are comprehensively discussed. In addition, the electrospun nanotechnology has been exploited to design drug release systems, investigate drug's pharmacokinetics and further develop DDS. The electrospun nanofibers improve bioactivity of various types of drugs including water-insoluble, soluble, anticancer and antibacterial drugs and genetic materials. In the end, the prospects and challenges in the process of designing drug-loaded electrospun nanofibers are discussed in detail. PMID- 29798693 TI - Views and experiences of care home staff on managing behaviours that challenge in dementia: a national survey in England. AB - AIM: To determine the views of care home (CH) staff in relation to experiencing and managing behaviour that challenges (BtC) in dementia and their experiences of training. METHOD: Cross-sectional survey using a self-report questionnaire, distributed to staff employed in a 20% sample of all registered dementia specialist CHs in England, either by postal or direct distribution. RESULTS: Questionnaires were returned from 352 care staff (25%), representing 5% of all dementia-specialist CHs, half were CH without nursing. Respondents estimated caring for 14,585 residents, 9,361 with dementia and 5,258 with BtC. 30.2% of residents with dementia were estimated as being prescribed a medicine to control BtC. BtC reported as experienced by most respondents were: shouting (96.6%), verbal aggression (96.3%) and physical aggression (95.7%), with physical aggression viewed as most difficult to manage. Top behaviours experienced every shift were: wandering (77.8%), perseveration (68.2%) and restlessness (68.2%). Approaches such as assessing residents, knowing them and treating them as individuals, identifying triggers, having time for them and using an appropriate style of communication, were viewed as key to managing BtC, rather than guideline specific interventions such as massage, aromatherapy and animal-assisted therapy. Only 38% agreed/strongly agreed medicines were useful to control BtC, which was related to the extent to which they were prescribed. Training was available, but variable in quality with on-line training being least useful and on-the job training most desirable. CONCLUSION: BtC are commonly and frequently experienced by care staff, who consider individual approaches, having time and good communication are key to successful management. PMID- 29798695 TI - Susceptibility of Candida glabrata biofilms to echinocandins: alterations in the matrix composition. AB - Candidiases are the most recurrent fungal infections, especially among immunosuppressed patients. Although Candida albicans is still the most widespread isolated species, non-Candida albicans Candida species have been increasing. The goal of this work was to determine the susceptibility of C. glabrata biofilms to echinocandins and to evaluate their effect on the biofilm matrix composition, comparing the results with other Candida species. Drug susceptibilities were assessed through the determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum biofilm eradication concentration (MBEC) of caspofungin (Csf) and micafugin (Mcf). The beta-1,3 glucans content of the matrices was assessed after contact with the drugs. The data suggest that, generally, after contact with echinocandins, the concentration of beta-1,3 glucans increased. These adjustments in the matrix composition of C. glabrata biofilms and the chemical differences between Csf and Mcf, seem responsible and may determine the effectivity of the drug responses. PMID- 29798696 TI - Epileptic seizure anticipation and localisation of epileptogenic region using EEG signals. AB - Electric activity of brain gets disturbed prior to epileptic seizure onset. Early prediction of an upcoming seizure can help to increase effectiveness of antiepileptic drugs. The scalp electroencephalogram signals contain information about the dynamics of brain and have been used to predict an upcoming seizure and localise its zone. The objective of this paper is to localise the epileptogenic region and predict an upcoming seizure at the earliest. To localise epileptogenic region, Electroencephalogram signals are categorised into four regions of brain (Frontal, Temporal, Parietal and Central). For each signal seventy-two (72) parameters in frequency domain have been extracted by using ten minute non overlapping window. Four prominent ratio parameters, gamma1/gamma5, gamma3/gamma1, theta/gamma2 and gamma4/theta have been identified as best parameters based on relative fisher score. Zone 2 shows the highest change in all the parameters as compared to the other zones. So, temporal region is identified as the epileptogenic region in this work. For prediction of the epileptic seizure machine learning algorithm artificial neural network (ANN) is proposed. The proposed machine learning algorithm has an accuracy of 92.3%, sensitivity of 100% and specificity of 83.3%. PMID- 29798697 TI - Regioselective synthesis of gentisyl alcohol-type marine natural products. AB - Gentisyl alcohol-type natural products, possessing various important biological properties, have been synthesized from 4-methoxyphenol by using a selective phenol monohydroxymethylation/monochlorination, a CAN oxidation and a sodium dithionite reduction as the key steps. The natural product synthesis is efficient, atom- and step-economical, and requires no protecting groups. PMID- 29798698 TI - Secukinumab in moderate-to-severe plaque psoriasis: a multi-center, retrospective, real-life study up to 52 weeks observation. AB - OBJECTIVES: To evaluate efficacy and safety of the anti-IL-17 drug secukinumab in a real-life large cohort of patients with moderate-to-severe plaque psoriasis in Central Italy. METHODS: Multicenter, retrospective study with an observation period of up to 52 weeks. Efficacy was assessed by Psoriasis Area and Severity Index (PASI) score; clinical and laboratory examinations were performed at baseline and at weeks 4, 12, 24, 36, and 52. RESULTS: A 90% and a 100% PASI score reduction (PASI90 and PASI100) were reported in 67.5% and 55% of patients at week 12, respectively. A rapid improvement of skin lesions was observed particularly in young patients and in patients naive to biologics: at week 4, the achievement of PASI90 and PASI100 was higher in younger patients (odds ratio [OR] 0.95, and 0.95; p = 0.003, and 0.005, respectively); PASI90 was achieved by 42.0% of patients naive to biologics and by 17.0% of patients with prior exposure to biologics (PBT) (OR 0.24; p = 0.001); and PASI100 was reached by 25.5% of naive patients and 9.8% of PBT (OR 0.28; p = 0.015).The drug was well tolerated. CONCLUSION: Secukinumab was effective in this real-life analysis, with rapid clinical improvement and long-term maintenance of results. PMID- 29798699 TI - Effect of filtering with time domain features for the detection of epileptic seizure from EEG signals. AB - Pattern recognition plays an important role in the detection of epileptic seizure from electroencephalogram (EEG) signals. In this pattern recognition study, the effect of filtering with the time domain (TD) features in the detection of epileptic signal has been studied using naive Bayes (NB) and supports vector machines (SVM). It is the first time the authors attempted to use TD features such as waveform length (WL), number of zero-crossings (ZC) and number of slope sign changes (SSC) derived from the filtered and unfiltered EEG data, and performance of these features is studied along with mean absolute value (MAV) which has been already attempted by the researchers. The other TD features which are attempted by the researchers such as standard deviation (SD) and average power (AVP) along with MAV are studied. A comparison is made in effect of filtering and without filtering for the University of Bonn database using NB and SVM for the TD features attempted first time along with MAV. The effect of individual and combined TD features is studied and the highest classification accuracy obtained in using direct TD features would be 99.87%, whereas it is 100% with filtered EEG data. The raw EEG data can be segmented and filtered using the fourth-order Butterworth band-pass filter. PMID- 29798700 TI - Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept. AB - OBJECTIVE: To examine the deterioration of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with abatacept over the long term. METHODS: We examined 131 patients with RA who had been treated with abatacept for more than 1 year. All patients underwent high-resolution computed tomographic (HRCT) scanning of the chest before administration of abatacept, and we examined deterioration of ILD over a follow-up period after administration of abatacept was initiated. RESULTS: Eleven patients (8.4%) showed deterioration of ILD over a mean follow-up period of 47.8 months. The factors related to ILD deterioration were use of methotrexate (MTX) [odds ratio 12.75, 95% confidence interval (CI) 1.09-148.77], and change in Krebs von-den Lungen-6 (odds ratio 1.00, 95% CI 1.00-1.01), according to multivariate logistic regression analysis. CONCLUSION: MTX in patients with RA treated with abatacept was a risk factor for deterioration of ILD. Discontinuation of MTX should be considered one of treatment reduction to prevent the deterioration of ILD. PMID- 29798702 TI - Iguratimod, a synthetic disease modifying anti-rheumatic drug inhibiting the activation of NF-kappaB and production of RANKL: Its efficacy, radiographic changes, safety and predictors over two years' treatment for Japanese rheumatoid arthritis patients. AB - OBJECTIVE: To elucidate the clinical and radiographic outcomes for rheumatoid arthritis (RA) patients treated with a synthetic disease-modifying antirheumatic drug, iguratimod (IGU). METHODS: Clinical outcomes for 213 RA patients treated with 25 mg/day oral IGU or 50 mg/day after 4 weeks of 25 mg/day treatment for one day to 104 weeks were assessed. RESULTS: A total of 142 active RA patients (DAS28 ESR >=3.2) treated for more than 12 weeks showed a significant reduction in both DAS and simplified disease activity index (SDAI) scores at week 4 (p < .001) to week 104. Good and moderate DAS responses were achieved in 54 (38%) and 66 (46%) patients, respectively. Total Genant-modified Sharp scores (GSS) of 31 patients at week 104 showed no progression (total GSS <=0.84: the smallest detectable change) in 16 (52%) patients with a mean score reduction (95%CI) of -4.3 (-8.1~ 0.5) (p < .05). Predictors were an early response, moderate disease activity at baseline, and male gender. Eleven of the 213 patients had gastric and/or duodenal ulcer. A peculiar haemorrhage was seen in two patients treated concomitantly with IGU and warfarin potassium. CONCLUSION: IGU treatment shows an early and sustained efficacy. Radiographically, no progression of GSS was evident in 16 (52%) patients at week 104. Gastric bleeding or gastric perforation warrants careful attention, especially in patients with concomitant use of both a non steroidal anti-inflammatory drug and oral prednisolone. PMID- 29798704 TI - I would like to do some research. Do you have a project? PMID- 29798706 TI - Effect of Lactobacillus strains on thymus and chemokine expression in keratinocytes and development of atopic dermatitis-like symptoms. AB - Lactobacillus strains, a major group of lactic acid bacteria, are representative food microorganisms that have many potential beneficial effects via their interactions with immune and intestinal epithelial cells. However, little is known about the effect of Lactobacillus strains on atopic dermatitis via keratinocytes, which comprise the physical barrier of the skin. In this study, we report that Lactobacillus strains have a significant suppressive effect on tumour necrosis factor (TNF)-alpha-induced expression and production of thymus and activation-regulated chemokine (TARC), a T helper 2 cell chemokine responsible for atopic dermatitis, in human keratinocytes. An RNA interference study showed that the effect of Lactobacillus reuteri strain Japan Collection of Microorganisms (JCM) 1112, the most suppressive strain, depended on the presence of Toll-like receptor 2 and the induction of A20 (also known as TNF-alpha-induced protein 3) and cylindromatosis in HaCaT cells. Topical application of a water soluble extract of homogenised JCM 1112 cells significantly suppressed the development of house dust mite-induced atopic skin lesions and TARC expression at the lesion sites in NC/Nga mice. Our study provides new insights into the use of Lactobacillus strains as suppressive agents against keratinocyte-involved atopic inflammation of the skin. PMID- 29798705 TI - Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro. AB - Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO 979C to prevent or reduce H. pylori-induced gastric inflammation in humans. PMID- 29798707 TI - The ascent of the blessed: regulatory issues on health effects and health claims for probiotics in Europe and the rest of the world. AB - The outcome of the first series of health claim applications for probiotics in Europe as evaluated by the European Food Safety Authority (EFSA) has, up to 2013 almost completely yielded negative results. All recent applications also have been rejected, including the latest on prevention of mastitis in breastfeeding mothers. In other developed countries, such as Switzerland, Japan and Canada, the health effects of probiotics, for which scientific evidence has been provided, can be communicated to potential consumers. The number of clinical trials with probiotics over recent years shows a trend to level off or even decline. At the same time, clinical research into the role of (gut) microbiota in a wide variety of diseases and conditions is booming. Ultimately, this may offer new indications for gut microbiota management by probiotics, prebiotics or other food supplements. PMID- 29798708 TI - Expanding the reach of probiotics through social enterprises. AB - The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a larger portion of the world's population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models. PMID- 29798709 TI - Values and value in simulated participant methodology: A global perspective on contemporary practices. AB - This article has been written for the 40th year of the publication of Medical Teacher. While we celebrate the contribution of simulated participants (SPs) to health professions education through values and value-based learning, we also offer critical reflection on elements of our practice, commencing with language. We argue for the use of the term simulated rather than standardized and acknowledge the dominant role of the SP as patient and the origins of the methodology. These shifts in terms and their implications in practice reflect changes in the conceptualization of SP-based methodology. Recently published standards for those who work with SPs (SP practitioners) are noted as an important milestone in our community's development. We consider contemporary practices addressing the complex notions of values and value in SP-based learning. We simultaneously refer to the work of SPs and SP practitioners. Phases of educational design including identifying learning objectives, scenario design, implementation, feedback and debriefing are used to illustrate methodological shifts. Within each of these phases, there are relational issues that have to date often gone unchecked and are under reported in literature. Finally, using the metaphor of a murmuration, we celebrate contemporary practices of the global SP practitioner community. PMID- 29798710 TI - Underreporting, crash severity and fault assignment of minor crashes in China - a study based on self-reported surveys. AB - Unreported minor crashes have importance as a surrogate for more serious crashes that require infrastructure, education, and enforcement strategies; and they still inflict damages. To study factors that influence underreporting, cause, and severity of minor crashes; a survey was performed in Kunming and Beijing to collect self-reported personal characteristics and crash history data of the three major urban road users in China: automobile drivers, bicycle riders and electric bike (e-bike) riders. Underreporting rates of automobile to automobile, automobile to non-motorized vehicle, and non-motorized vehicle to non-motorized vehicle crashes are 56%, 77% and 94%, respectively. Minor crashes with higher reported injury severity levels are more likely to be reported. E-bike riders without a driver's license are more likely to cause crashes. Licensing and education could be an effective way to reduce their crashes. The party that is not at fault in a crash is more likely to sustain high level of injury. PMID- 29798712 TI - 43rd Annual Southern Pediatric Neurology Society Meeting, New Orleans, Louisiana. PMID- 29798711 TI - Individualized antithrombotic therapy in high-risk cardiovascular patients. AB - Recent guidelines suggest dual antiplatelet therapy (DAPT) after 'drug-eluting' stent (DES) implantation for 6 months in stable patients and for 12 months in patients after acute coronary syndrome. Serious complications after stent implantation include stent thrombosis, recurrent myocardial infarction, ischemic stroke, cardiovascular death and bleeding. These complications also occur beyond 1 year after coronary intervention. Thus, it is important to consider whether a prolonged DAPT (>12 months after percutaneous coronary intervention) is of benefit to lower thrombo-ischemic events in high-risk patients. This review addresses the results of recent randomized clinical studies (DAPT, ITALIC, OPTIDUAL and PEGASUS) and meta-analyses to support the author's view of which patient collectives might benefit from prolonged DAPT. PMID- 29798713 TI - Collaborative use of virtual patients after a lecture enhances learning with minimal investment of cognitive load. AB - BACKGROUND: The use of virtual patients (VPs), due to their high complexity and/or inappropriate sequencing with other instructional methods, might cause a high cognitive load, which hampers learning. AIM: To investigate the efficiency of instructional methods that involved three different applications of VPs combined with lectures. METHOD: From two consecutive batches, 171 out of 183 students have participated in lecture and VPs sessions. One group received a lecture session followed by a collaborative VPs learning activity (collaborative deductive). The other two groups received a lecture session and an independent VP learning activity, which either followed the lecture session (independent deductive) or preceded it (independent inductive). All groups were administrated written knowledge acquisition and retention tests as well as transfer tests using two new VPs. All participants completed a cognitive load questionnaire, which measured intrinsic, extraneous and germane load. Mixed effect analysis of cognitive load and efficiency using the R statistical program was performed. RESULTS: The highest intrinsic and extraneous load was found in the independent inductive group, while the lowest intrinsic and extraneous load was seen in the collaborative deductive group. Furthermore, comparisons showed a significantly higher efficiency, that is, higher performance in combination with lower cognitive load, for the collaborative deductive group than for the other two groups. CONCLUSION: Collaborative use of VPs after a lecture is the most efficient instructional method, of those tested, as it leads to better learning and transfer combined with lower cognitive load, when compared with independent use of VPs, either before or after the lecture. PMID- 29798714 TI - Is prenatal sex selection associated with lower female child mortality? AB - I examine whether prenatal sex selection has substituted postnatal excess female mortality by analysing the dynamics of child sex ratios between 1980 and 2015 using country-level life table data. I decompose changes in child sex ratios into a 'fertility' component attributable to prenatal sex selection and a 'mortality' component attributable to sex differentials in postnatal survival. Although reductions in numbers of excess female deaths have accompanied increases in missing female births in all countries experiencing the emergence of prenatal sex selection, relative excess female mortality has persisted in some countries but not others. In South Korea, Armenia, and Azerbaijan, mortality reductions favouring girls accompanied increases in prenatal sex selection. In India, excess female mortality was much higher and largely stable as prenatal sex selection emerged, but slight reductions were seen in the 2000s. In China, although absolute measures showed reductions, relative excess female mortality persisted as prenatal sex selection increased. PMID- 29798715 TI - Personalized medicine in brain metastases: a plea for more translational studies. PMID- 29798717 TI - Thank you reviewer list. PMID- 29798718 TI - HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass. PMID- 29798716 TI - Genetic polymorphism in RANK is associated with mandibular size. AB - OBJECTIVE: The aim of this study was to evaluate the association between genetic polymorphisms in RANK, RANKL and OPG with maxillary and mandibular dimensions in humans. DESIGN: DNA extracted from saliva and the rs3826620, rs9594738 and rs2073618 polymorphisms in RANK, RANKL and OPG, respectively, were analysed by real-time PCR. Four linear measurements (Co-Gn, GoPg, Co-Go and PTM-A) from lateral cephalograms were examined for the evaluation of craniofacial measurements. ANOVA testing and a multivariate linear regression analysis, adjusted for age and gender, were used for statistical analysis, with an alpha of 5%. Hardy-Weinberg equilibrium was also evaluated using the chi-square test within each polymorphism. SETTING: School of Dentistry of Ribeirao Preto, University of Sao Paulo. PARTICIPANTS: A total of 100 unrelated non-syndromic Brazilian Caucasian subjects were included in this study. RESULTS: The polymorphism in RANK was associated with a higher Go-Pg measurement (p = .039). In the multivariate analysis, adjusted for age and gender, the polymorphism in RANK was associated with Go-Pg (p = .017) and Co-Gn (p = .043). CONCLUSION: The polymorphism rs3826620 in RANK is associated with the mandibular size. PMID- 29798719 TI - Cutting for the stone (transperineal lithotomy). PMID- 29798720 TI - Cut sutures? Too long or too short! PMID- 29798721 TI - Letter to the Editor. PMID- 29798722 TI - Resuscitation issues in hospital. PMID- 29798724 TI - News Update. PMID- 29798723 TI - Grasp the nettle. PMID- 29798726 TI - Altered folate binding protein expression and folate delivery are associated with congenital hydrocephalus in the hydrocephalic Texas rat. AB - Hydrocephalus (HC) is an imbalance in cerebrospinal fluid (CSF) secretion/absorption resulting in fluid accumulation within the brain with consequential pathophysiology. Our research has identified a unique cerebral folate system in which depletion of CSF 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is associated with cortical progenitor cell-cycle arrest in hydrocephalic Texas (H-Tx) rats. We used tissue culture, immunohistochemistry, in-situ PCR and RT-PCR and found that the in-vitro proliferation of arachnoid cells is highly folate-dependent with exacerbated proliferation occurring in hydrocephalic CSF that has low FDH but high folate-receptor-alpha (FRalpha) and folate. Adding FDH to this CSF prevented aberrant proliferation indicating a regulatory function of FDH on CSF folate concentration. Arachnoid cells have no detectable mRNA for FRalpha or FDH, but FDH mRNA is found in the choroid plexus (CP) and CSF microvesicles. Co-localization of FDH, FRalpha and folate suggests important functions of FDH in cerebral folate transport, buffering and function. In conclusion, abnormal CSF levels of FDH, FRalpha and folate inhibit cortical cell proliferation but allow uncontrolled arachnoid cell division that should increase fluid absorption by increasing the arachnoid although this fails in the hydrocephalic brain. FDH appears to buffer available folate to control arachnoid proliferation and function. PMID- 29798727 TI - Consider Advance Care Planning for Transplant Candidates. PMID- 29798728 TI - High Expression of FOXP3 mRNA in Blood and Urine as a Predictive Marker in Kidney Transplantation. AB - BACKGROUND: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles. METHODS: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction. RESULTS: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes. CONCLUSION: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction. PMID- 29798729 TI - Improvement of the developmental competence of canine oocyte using caffeine supplementation during IVM at different maturation time. AB - SummaryThe aim of the current study was to investigate the effect of caffeine supplementation during in vitro maturation (IVM) for different maturation times on the developmental potential of canine oocytes recovered from ovariohysterectomized bitches. The recovered cumulus-oocytes complexes were in vitro matured for 72 h. Here, 10 mM caffeine was added to the maturation medium for different incubation times (caffeine from 0-72 h maturation, caffeine for the first 24 h of maturation only, caffeine addition from 24 to 48 h maturation time, caffeine addition from 48 to 72 h maturation or in caffeine-free medium, control group). The matured oocytes were in vitro fertilized using frozen-thawed spermatozoa. The presumptive zygotes were in vitro cultured in synthetic oviductal fluid medium for 5 days. The results showed that both maturation and fertilization rates were significantly higher (P ? 0.05) using caffeine-treated medium for the first 24 h of maturation compared with the control and other two groups of caffeine treatment (from 24 to 48 h and from 48 to 72 h), whereas use of caffeine-treated medium for a 0-72 h incubation time did not affect these rates (P > 0.05). Interestingly, the matured oocytes in caffeine-supplemented medium for the first 24 h or from 0-72 h showed a significant (P ? 0.05) increase in the total number of cleaved embryos compared with the control group. In conclusion, supplementation of the maturation medium with 10 mM caffeine for the first 24 h of maturation or during the whole maturation time (0-72 h) improved nuclear maturation and subsequent embryo development preimplantation following in vitro fertilization. PMID- 29798731 TI - Dietary arginine affects growth, gut morphology, oxidation resistance and immunity of hybrid grouper (Epinephelus fuscoguttatus?*Epinephelus lanceolatus?) juveniles. AB - An 8-week growth trial was conducted to evaluate the effects of dietary arginine (Arg) levels on growth, gut morphology, oxidation resistance and immunity of hybrid grouper (Epinephelus fuscoguttatus?*Epinephelus lanceolatus?) juveniles. Seven isoenergetic (1465 kJ (350 kcal)/100-g DM), isoproteic (53.5 % of DM) and isolipidic (7 % of DM) experimental diets were formulated to contain graded Arg levels ranging from 1.9 to 4.7 % (dry weight) at approximately 0.5 % increments. Each diet was randomly assigned to triplicate groups of 16 juvenile fish (average initial body weight: 11.7 (sd 0.1) g) and was administered twice daily (08.00 and 16.00 hours). After the growth trial, all remaining fish were fed their prescribed diets for 2 d and then exposed to 4.5 mg Cu2+/l water for 36 h. Results showed that growth performance and feed utilisation of experimental fish were significantly affected by different dietary Arg levels. Weight gain % (WG%) of fish was increased as dietary Arg increased, reaching a peak value at 3.8 % dietary Arg level, and when dietary Arg level increased to 4.7 % WG% was reduced. Fish fed 1.9 and 2.2 % dietary Arg levels had higher daily feed intake compared with fish fed other dietary Arg levels. Feed conversion ratios in fish fed 1.9, 2.2, 2.7 and 4.7 % dietary Arg levels were higher than those in fish fed 3.1, 3.8 and 4.1 % dietary Arg levels. Protein efficiency ratio and protein productive value (PPV) increased with an increase in dietary Arg, up to a peak value at 3.8 % dietary Arg level, above which these parameters declined. On the basis of quadratic regression analysis of weight gain % (WG%) or PPV against dietary Arg levels, the optimal dietary Arg requirement for hybrid grouper was estimated to be 3.65 %. Fish fed 3.8 % dietary Arg had higher whole-body and muscle protein contents compared with fish fed other dietary Arg levels. Fish fed 3.8 and 4.1 % dietary Arg levels had higher levels of mRNA for insulin-like growth factor-I and target of rapamycin in the liver compared with fish fed other dietary Arg levels. Hepatic S6 kinase 1 mRNA expression in fish fed 3.8 % dietary Arg level was higher than that in fish fed any of the other dietary Arg levels. Gut morphology, hepatic antioxidant indices and immune indices in serum and head kidney were significantly influenced by dietary Arg levels. In conclusion, the optimal dietary Arg requirement for hybrid grouper was estimated to be 3.65 %, and suitable dietary Arg supplementations improved gut morphology and oxidation resistance of hybrid grouper. PMID- 29798730 TI - Telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder: systematic review. AB - BACKGROUND: The mental and physical health of individuals with a psychotic illness are typically poor. Access to psychosocial interventions is important but currently limited. Telephone-delivered interventions may assist. In the current systematic review, we aim to summarise and critically analyse evidence for telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (i) relapse, (ii) adherence to psychiatric medication and/or (iii) modifiable cardiovascular disease risk behaviours. METHODS: Ten peer-reviewed and four grey literature databases were searched for English-language studies examining psychosocial telephone-delivered interventions targeting relapse, medication adherence and/or health behaviours in adults with a psychotic disorder. Study heterogeneity precluded meta-analyses. RESULTS: Twenty trials [13 randomised controlled trials (RCTs)] were included, involving 2473 participants (relapse prevention = 867; medication adherence = 1273; and health behaviour = 333). Five of eight RCTs targeting relapse prevention and one of three targeting medication adherence reported at least 50% of outcomes in favour of the telephone-delivered intervention. The two health behaviour RCTs found comparable levels of improvement across treatment conditions. CONCLUSIONS: Although most interventions combined telephone and face to-face delivery, there was evidence to support the benefit of entirely telephone delivered interventions. Telephone interventions represent a potentially feasible and effective option for improving key health priorities among people with psychotic disorders. Further methodologically rigorous evaluations are warranted. PMID- 29798732 TI - Transition from blastomere to trophectoderm biopsy: comparing two preimplantation genetic testing for aneuploidies strategies. AB - SummaryShortly after the implementation of comprehensive chromosome screening (CCS) techniques for preimplantation genetic testing for aneuploidies (PGT-A), the discussion about the transition from day 3 to blastocyst stage biopsy was initiated. Trophectoderm biopsy with CCS is meant to overcome the limitations of cleavage-stage biopsy and single-cell analysis. The aim of this study was to assess the results obtained in our PGT-A programme after the implementation of this new strategy. Comparisons between the results obtained in 179 PGT-A cycles with day 3 biopsy (D+3) and fresh embryo transfer, and 204 cycles with trophectoderm biopsy and deferred (frozen-thawed) embryo transfer were established. Fewer embryos were biopsied and a higher euploidy rate was observed in the trophectoderm biopsy group. No differences in implantation (50.3% vs. 61.4%) and clinical pregnancy rate per transfer (56.1% vs. 65.3%) were found. Although the mean number of euploid embryos per cycle did not differ between groups (1.5 +/- 1.7 vs. 1.7 +/- 1.8), the final number of euploid blastocysts available for transfer per cycle was significantly higher in the trophectoderm biopsy group (1.1 +/- 1.3 vs. 1.7 +/- 1.8). This factor led to an increased cumulative live birth rate in this last group (34.1% vs. 44.6%). Although both strategies can offer good results, trophectoderm biopsy offers a more robust diagnosis and the intervention is less harmful for the embryos so more euploid blastocysts are finally available for transfer and/or vitrification. PMID- 29798733 TI - The effects of gender, age, schooling, and cultural background on the identification of facial emotions: a transcultural study. AB - : ABSTRACTBackground:Social cognition tasks, such as identification of emotions, can contribute to the diagnosis of neuropsychiatric disorders. The wide use of Facial Emotion Recognition Test (FERT) is hampered by the absence of normative dataset and by the limited understanding of how demographic factors such as age, education, gender, and cultural background may influence the performance on the test. METHODS: We analyzed the influence of these variables in the performance in the FERT from the short version of the Social and Emotional Assessment. This task is composed by 35 pictures with 7 different emotions presented 5 times each. Cognitively healthy Brazilian participants (n = 203; 109 females and 94 males) underwent the FERT. We compared the performance of participants across gender, age, and educational subgroups. We also compared the performance of Brazilians with a group of French subjects (n = 60) matched for gender, age, and educational level. RESULTS: There was no gender difference regarding the performance on total score and in each emotion subscore in the Brazilian sample. We found a significant effect of aging and schooling on the performance on the FERT, with younger and more educated subjects having higher scores. Brazilian and French participants did not differ in the FERT and its subscores. Normative data for employing the FERT in Brazilian population is presented. CONCLUSIONS: Data here provided may contribute to the interpretation of the results of FERT in different cultural contexts and highlight the common bias that should be corrected in the future tasks to be developed. PMID- 29798734 TI - Metabolic side effects of atypical antipsychotics in older adults. AB - : ABSTRACTBackground:The atypical antipsychotics (AAPs) are associated with a recognized class effect of glucose and lipid dysregulation. The use of these medications is rapidly increasing in elderly patients with, and without, dementia. However, the metabolic risks specific to elderly remain poorly studied. METHODS: Design: A case-control study. SETTING: Psychogeriatric service in Auckland, New Zealand. PARTICIPANTS: Elderly patients either receiving AAP treatment (cases) or not (controls) between 1 Jan 2008 and 1 Jan 2014. MAIN OUTCOME MEASURES: metabolic data of glucose, HbA1c, lipids, and cardiovascular events and death. The data were analyzed using t-tests and linear regression models for each metabolic outcome. RESULTS: There were 330 eligible cases and 301 controls from a total study population of 5,307. There was a statistically significant change in the HbA1c over time, within the cases group of -1.14 mmol/mol (p = 0.018, 95% CI -0.19 to -2.09). Also statistically significant was the reduction in total cholesterol of -0.13 mmol/L (p = 0.036, 95% CI -0.008 to 0.245). The only significant difference found between cases and controls was in the change in cholesterol ratio of 0.16 mmol/L between groups (95%CI 0.01-0.31, p = 0.036). CONCLUSIONS: AAP use was not associated with any clinically significant change in metabolic outcomes in this study population. PMID- 29798735 TI - The unmet support needs of carers of older Australians: prevalence and mental health. AB - : ABSTRACTBackground:Population aging places greater demands on the supply of informal carers. The aims of this study were to examine (1) the types of unmet support needs of carers of older Australians and (2) the association of unmet needs with mental health. METHODS: Utilizing new data from the 2015 Australian Bureau of Statistics (ABS) Survey of Disability, Ageing and Carers, we calculated the prevalence of carers experiencing specific and multiple unmet needs for support, using single and multiple item measures. Logistic regression models were fitted to examine the association between unmet needs and psychological distress (using the Kessler psychological distress scale), once demographic and health factors were controlled for. RESULTS: In 2015, 35% of carers of older Australians cited at least one unmet need for support. Among this group, almost two-thirds cited multiple unmet support needs (64.7%). The most prevalent types of unmet needs included financial (18%), physical (13%), and emotional support (12%), as well as additional respite care and support to improve carer health (12%). After controlling for demographic and health characteristics of the carer, having any unmet need for support increased the odds of psychological distress by twofold (OR = 2.20, 95% CI = 1.65, 2.94). With each successive unmet need for support, the odds of psychological distress increased 1.37 times (OR = 1.36, 95% CI = 1.22, 1.54). Those who had received assistance with care, but required further support were 1.95 times more likely (OR = 1.95, 95% CI = 1.17, 3.24) to be in distress and those who had not received care assistance were about 2.4 times more likely (OR = 2.38 95% OR = 1.56, 3.62) to be in distress relative to those with no unmet need. CONCLUSIONS: Addressing unmet support needs of carers is important, not only for the planning of services for carers in an aging population, but also because of the association between unmet support needs and carers mental health. PMID- 29798736 TI - Strategies employed by older people to manage loneliness: systematic review of qualitative studies and model development. AB - : ABSTRACTObjectives:To (i) systematically identify and review strategies employed by community dwelling lonely older people to manage their loneliness and (ii) develop a model for managing loneliness. METHODS: A narrative synthesis review of English-language qualitative evidence, following Economic and Social Research Council guidance. Seven electronic databases were searched (1990-January 2017). The narrative synthesis included tabulation, thematic analysis, and conceptual model development. All co-authors assessed eligibility of final papers and reached a consensus on analytic themes. RESULTS: From 3,043 records, 11 studies were eligible including a total of 502 older people. Strategies employed to manage loneliness can be described by a model with two overarching dimensions, one related to the context of coping (alone or with/in reference to others), the other related to strategy type (prevention/action or acceptance/endurance of loneliness). The dynamic and subjective nature of loneliness is reflected in the variety of coping mechanisms, drawing on individual coping styles and highlighting considerable efforts in managing time, contacting others, and keeping loneliness hidden. Cognitive strategies were used to re-frame negative feelings, to make them more manageable or to shift the focus from the present or themselves. Few unsuccessful strategies were described. CONCLUSION: Strategies to manage loneliness vary from prevention/action through to acceptance and endurance. There are distinct preferences to cope alone or involve others; only those in the latter category are likely to engage with services and social activities. Older people who deal with their loneliness privately may find it difficult to articulate an inability to cope. PMID- 29798737 TI - A new music therapy engagement scale for persons with dementia. AB - : ABSTRACTObjectives:To develop and validate a new scale to assess music therapy engagement in persons with dementia (PWDs). DESIGN: A draft scale was derived from literature review and >2 years of qualitative recording of PWDs during music therapy. Content validity was attained through iterative consultations, trial sessions, and revisions. The final five-item Music Therapy Engagement scale for Dementia (MTED) assessed music and non-music related elements. Internal consistency and inter-rater reliability were assessed over 120 music therapy sessions. MTED was validated with the Greater Cincinnati Chapter Well-being Observation Tool, Holden Communication Scale, and Participant Engagement Observation Checklist - Music Sessions. SETTING AND PARTICIPANTS: A total of 62 PWDs (83.2 +/- 7.7 years, modified version of the mini-mental state examination = 13.2/30 +/- 4.1) in an acute hospital dementia unit were involved. RESULTS: The mean MTED score was 13.02/30 +/- 4.27; internal consistency (Cronbach's alpha = 0.87) and inter-rater reliability (intra-class correlation = 0.96) were good. Principal component analysis revealed a one-factor structure with Eigen value > 1 (3.27), which explained 65.4% of the variance. MTED demonstrated good construct validity. The MTED total score correlated strongly with the combined items comprising Pleasure, Interest, Sadness, and Sustained attention of the Greater Cincinnati Chapter Well-being Observation Tool (rs = 0.88, p < 0.001). CONCLUSIONS: MTED is a clinically appropriate and psychometrically valid scale to evaluate music therapy engagement in PWDs. PMID- 29798738 TI - Mild cognitive impairment and dementia in older patients attending a general hospital in south India: DSM-5 standards and correlates. AB - : ABSTRACTBackground and Aims:The changes in DSM-5 diagnostic criteria for dementia (Major neurocognitive disorder (NCD)) and mild cognitive impairment (mild NCD) mandate a re-evaluation of screening instruments. This study attempted to validate screening instruments, identify optimum threshold, and describe their indices of efficacy. METHOD: Consecutive people above the age of 65 years attending the outpatient department of a general hospital were recruited. They were assessed using the Mini-Mental State Examination and the Vellore Screening Instruments for Dementia and were evaluated against the DSM-5 standard. Bivariate and multivariate statistics were obtained. Receiver-operating-characteristic curves were drawn, optimum thresholds obtained, sensitivity, specificity, and predictive values calculated. RESULTS: One hundred and thirty four older people were recruited. The majority were women, married, with low levels of education, not employed, living with family, and had medical co-morbidity. A minority satisfied DSM-5 criteria for major (1.5%) and mild NCD (36.5%). The factors associated with NCD were older age, fewer years of education, and lower socio economic status. MMSE, VSID patient, and VSID informant scores were significantly associated with NCD. The indices of efficacy for the MMSE and VSID patient version were modest for identifying Mild NCD. However, their performance in identifying major NCD was better. Nevertheless, optimal thresholds for recognition differed markedly from their originally recommended cut-offs. CONCLUSIONS: The DSM-5 standards, with new and different cognitive domains, mandate a revaluation and recalibration of existing screening instruments. Ideally, new screening instruments, which match the cognitive domains and DSM-5 standard should be developed. PMID- 29798739 TI - The Fountain of Health: effective health promotion knowledge transfer in individual primary care and group community-based formats. AB - : ABSTRACTBackground:The Fountain of Health (FoH) initiative is a knowledge transfer (KT) project on the science of brain health and resilience promotion, in alignment with positive psychiatry. OBJECTIVES: Assess the effectiveness of FoH KT delivered in individual and group-based formats. DESIGN: Pre- and post intervention quality assurance survey of FoH KT. SETTING: Interventions occurred in Nova Scotia, Canada. PARTICIPANTS: Adults over age 50 years without pre existing dementia were targeted. A total of 92 participants received FoH KT in individualized (n = 41) and group-based (n = 51) formats. INTERVENTION: FoH KT (e.g. sharing evidence, lifestyle coaching, and goal setting) using a range of KT supports (e.g. FoH website, paper materials) was delivered to (1) individual patients by primary care clinicians and (2) community-based groups by lay leaders. MEASUREMENTS: The main outcome measure was participant pre- and post quality assurance self-reports. RESULTS: Improvements were found in participant awareness of FoH, knowledge of evidence-based mental health promotion initiatives, and in application of this information in daily life in both individual and group-based settings. Improvements in participant knowledge about epigenetic factors that impact health and confidence with health behavior goal setting were reported in both contexts. Changes in self-perceptions of aging scores reached significance in the group intervention. CONCLUSIONS: FoH KT produced short-term positive self-reported changes in participants in both individual and group formats. Larger control studies with long-term follow up are needed to better assess effects of both individual and group formats of FoH KT and longer term impacts on health behaviors and outcomes. PMID- 29798740 TI - Successful aging in Spanish older adults: the role of psychosocial resources. AB - : ABSTRACTBackground:Psychological and social resources such as extraversion, optimism, social support, or social networks contribute to adaptation and to successful aging. Building on assumptions derived from successful aging and from the developmental adaptation models, this study aims to analyze the joint impact of different psychosocial resources, such as personality, social relations, health, and socio-demographic characteristics on life satisfaction in a group of people aged 65 years-old and older from Spain. METHOD: A cross-sectional survey using non-proportional quota sampling was carried out. The sample comprised 406 community-dwelling older adults (M = 74.88, SD = 6.75). In order to collect the data, face-to-face interviews were individually conducted. A structural equation model (SEM) was carried out using the PLS software. RESULTS: The results of the SEM model showed that, within this sample, psychosocial variables explain 47.4% of the variance in life satisfaction. Social relations and personality, specifically optimism, were strongly related with life satisfaction, while health status and socio-demographic characteristics were modestly associated with life satisfaction. CONCLUSIONS: Findings support the view that psychosocial resources are important for successful aging and therefore should be included in successful aging models. Furthermore, interventions aimed at fostering successful aging should take into account the role of psychosocial variables. PMID- 29798741 TI - How couples with dementia experience healthcare, lifestyle, and everyday decision making. AB - : ABSTRACTObjectives:Recent research has demonstrated the challenges to self identity associated with dementia, and the importance of maintaining involvement in decision-making while adjusting to changes in role and lifestyle. This study aimed to understand the lived experiences of couples living with dementia, with respect to healthcare, lifestyle, and "everyday" decision-making. DESIGN: Semi structured qualitative interviews using Interpretative Phenomenological Analysis as the methodological approach. SETTING: Community and residential care settings in Australia. PARTICIPANTS: Twenty eight participants who self-identified as being in a close and continuing relationship (N = 13 people with dementia, N = 15 spouse partners). Nine couples were interviewed together. RESULTS: Participants described a spectrum of decision-making approaches (independent, joint, supported, and substituted), with these approaches often intertwining in everyday life. Couples' approaches to decision-making were influenced by "decisional," "individual," "relational," and "external" factors. The overarching themes of "knowing and being known," "maintaining and re-defining couplehood" and "relational decision-making," are used to interpret these experiences. The spousal relationship provided an important context for decision-making, with couples expressing a history and ongoing preference for joint decision-making, as an integral part of their experience of couplehood. However, the progressive impairments associated with dementia presented challenges to maintaining joint decision-making and mutuality in the relationship. CONCLUSIONS: This study illustrates relational perspectives on decision-making in couples with dementia. Post-diagnostic support, education resources, proactive dyadic interventions, and assistance for spouse care partners may facilitate more productive attempts at joint decision-making by couples living with dementia. PMID- 29798742 TI - Sensory loss and suicide ideation in older adults: findings from the Three-City cohort study. AB - : ABSTRACTObjectives:To examine the longitudinal risk of vision loss (VL) or hearing loss (HL) for experiencing suicidal ideation in older adults. DESIGN: The Three-City study, examining data from three waves of follow-up (2006-2008, 2008 2010, and 2010-2012). SETTING: Community-dwelling older French adults. PARTICIPANTS: N = 5,438 adults aged 73 years and over. MEASUREMENTS: Suicidality was assessed by the Mini-International Neuropsychiatric Interview, Major Depressive Disorder module. Mild VL was defined as Parinaud of 3 or 4 and severe VL as Parinaud >4. Mild HL was self-reported as difficulty understanding a conversation and severe HL as inability to understand a conversation. RESULTS: Severe VL was associated with an increased risk of suicidal ideation at baseline (OR = 1.59, 95% CIs = 1.06-2.38) and over five years (OR = 1.65, 95% CIs = 1.05 2.59). Mild and severe HL were associated with an increased risk of suicidal ideation, both at baseline (OR = 1.29, 95% CIs = 1.03-1.63; OR = 1.78, 95% CIs = 1.32-2.40) and over five years (OR = 1.47, 95% CIs = 1.17-1.85; OR = 1.97, 95% CIs = 1.44-2.70). CONCLUSION: Sensory losses in late life pose a risk for suicidal ideation. Suicidality requires better assessment and intervention in this population. PMID- 29798743 TI - Increased plasma complement factor H is associated with geriatric depression. AB - : ABSTRACTBackground:Complement factor H (CFH) plays a key role in regulating the cascade of the alternative pathway of the complement system. Dysregulation of CFH may be involved in the pathophysiology of various inflammation-mediated diseases including neuropsychiatric illnesses. This study aimed to investigate this relationship by examining determining CFH levels in elderly individuals with and without depression. METHODS: A total of 152 elderly individuals (major depressive disorder (MDD) group, n = 76; comparison sample, n = 76) were selected from the Ansan Geriatric study. The plasma level of CFH was measured. MDD was diagnosed with the Mini-International Neuropsychiatric Interview as per DSM-IV criteria. The severity of depression was evaluated with the geriatric depression scale (GDS). Mean CFH levels were compared using the Mann-Whitney U test. After adjusting for possible confounding factors including age, sex, marital status, education, alcohol use, hemoglobin levels, and the Korean version of the Mini Mental State Examination (MMSE-KC), a multiple regression analysis was conducted. The GDS score and plasma level of CFH were analyzed using Spearman's correlation. RESULTS: Plasma CFH level was significantly higher in individuals with MDD than in the comparison sample (289.51 +/- 21.16 vs. 339.67 +/- 66.23, p < 0.001). In a regression model adjusted for possible confounders, CFH was significantly associated with geriatric depression (p < 0.001). CFH levels were not significantly related to GDS scores in the depressed group. CONCLUSION: This study revealed an association between high plasma levels of CFH and geriatric depression, thereby suggesting the alternative pathway of the complement system contributing to the development of geriatric depression. PMID- 29798744 TI - Plasmodium falciparum Plasmepsin 2 Duplications, West Africa. AB - Dihydroartemisinin/piperaquine (DHA/PPQ) is increasingly deployed as antimalaria drug in Africa. We report the detection in Mali of Plasmodium falciparum infections carrying plasmepsin 2 duplications (associated with piperaquine resistance) in 7/65 recurrent infections within 2 months after DHA/PPQ treatment. These findings raise concerns about the long-term efficacy of DHA/PPQ treatment in Africa. PMID- 29798745 TI - Therapeutic and Transmission-Blocking ?Efficacy of Dihydroartemisinin/Piperaquine and Chloroquine against Plasmodium vivax Malaria, Cambodia. AB - We assessed the efficacy of standard 3-day courses of chloroquine and dihydroartemisinin/piperaquine against Plasmodium vivax malaria. Compared with chloroquine, dihydroartemisinin/piperaquine was faster in clearing asexual P. vivax parasites and blocking human-to-mosquito transmission. This drug combination was also more effective in preventing potential recurrences for >2 months. PMID- 29798747 TI - Erratum, Vol. 15, May 3 Release. AB - This corrects the article DOI: 10.5888/pcd15.160471. PMID- 29798746 TI - Phylogeny of Yellow Fever Virus, Uganda, 2016. AB - In April 2016, a yellow fever outbreak was detected in Uganda. Removal of contaminating ribosomal RNA in a clinical sample improved the sensitivity of next generation sequencing. Molecular analyses determined the Uganda yellow fever outbreak was distinct from the concurrent yellow fever outbreak in Angola, improving our understanding of yellow fever epidemiology. PMID- 29798749 TI - [Syphilis]. AB - Syphilis is a sexually transmitted infection caused by the spirochaete Treponema pallidum. Syphilis re-emerged worldwide in the late 1990s, and hereafter increasing rates of syphilis were seen also in Denmark. Currently, around 700 cases are diagnosed yearly in Denmark, and syphilis is mainly encountered among men, who have sex with men. However, because of the risk of congenital infection screening of pregnant women has been introduced. Syphilis gives rise to highly variable symptoms such as chancre, skin rashes and fever or latent infection. The recommended treatment is intramuscular administration of penicillin. PMID- 29798748 TI - One year in review 2018: novelties in the treatment of rheumatoid arthritis. AB - The current approach to treatment of rheumatoid arthritis (RA) includes early and aggressive intervention aiming to reach early and persistent low disease activity and remission. New drugs have improved the therapeutic armamentarium of rheumatologists, providing new options for patients. Beyond these innovations, new evidence has improved the safety of therapies and provided tools for the optimisation of long-term management of RA. This paper reviews the most relevant studies published over the last year in the field of treatment of RA. PMID- 29798750 TI - [Genital herpes]. AB - Genital herpes is a common sexually transmissible infection (STI) caused by herpes simplex virus (HSV). Clinically, the infection presents with genital ulcers but may also be asymptomatic. The risk of genital HSV infection is associated with increasing number of sex partners, previous infection with another STI and female sex. The cornerstone of treatment is systemic antivirals such as acyclovir. Counselling on transmission and recurrence risks is essential, and psychological distress is often a consequence of the disease. PMID- 29798751 TI - [Ano-genital warts are more than benign lesions]. AB - Ano-genital warts are in general considered as benign lesions, as they are mostly caused by the non-oncogenic HPV types 6 and 11. In this review, there is a focus on the problematic issues, that these lesions and their treatments can cause. Both topical and ablative treatments are associated with side effects, and the varying effect of the treatments combined with an uncertain timeline to clearance are known to cause psychological distress. Vaccination against HPV-6 and -11 has been shown to reduce the incidence of this troublesome infection substantially in both women and men in countries with high vaccine coverage. PMID- 29798752 TI - [Gonorrhoea]. AB - Gonorrhoea, a condition on the rise, is associated with high morbidity, and the possibility of reproductive sequelae has become a public health problem in Denmark. It is important to perform swabs for gonorrhoea from all relevant anatomical locations, whether or not there are symptoms. Through complete microbiological diagnostics, treatment with recommended antibiotics and partner detection, infection chains can be broken. Whole-genome sequencing in real time will identify outbreaks in high-risk populations. PMID- 29798753 TI - [Sexually transmitted Mycoplasma genitalium infection is difficult to treat]. AB - Mycoplasma genitalium infection is sexually transmitted, and it is almost as common as chlamydia in most European settings. Symptoms are indistinguishable from those of chlamydia, and late sequelae are believed to be similar. Treatment of M. genitalium infection is complicated due to widespread antimicrobial resistance not only to first-line azithromycin but now also increasingly to second-line moxifloxacin, leaving no other antibiotics registered in Denmark available for effective treatment. In the absence of available antimicrobials, screening of asymptomatic individuals should be avoided. PMID- 29798754 TI - [Chlamydia in Denmark]. AB - Oculo-genital chlamydia caused by Chlamydia trachomatis is the most frequent sexually transmitted infection. The number of laboratory verified cases increases steadily in Denmark. This is due to an increased testing activity but also increased positivity rates. Men show substantially lower test rates than women albeit higher positivity rates and seem to constitute an important reservoir for a continued high prevalence of chlamydia. Screening and treatment of especially younger sexually active individuals, not at least men, is vital in controlling the disease. PMID- 29798755 TI - [Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male]. AB - This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a se xually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped. PMID- 29798756 TI - You Are What You Tweet: Navigating Legal Issues in Social Media for Interventional Radiologists. PMID- 29798759 TI - Patient-Derived Xenograft Tumor Models: Overview and Relevance to IR. PMID- 29798760 TI - Gastrointestinal Elimination of a Hepatocellular Carcinoma. PMID- 29798762 TI - Role of Angiography in the Diagnosis and Treatment of Gastrointestinal Bleeding: Historical Perspective. PMID- 29798761 TI - Role of Biodegradable Stents as Part of Treatment of Biliary Strictures after Pediatric and Adult Liver Transplantation: An Observational Single-Center Study. AB - This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%). PMID- 29798763 TI - Ventral hernia and pregnancy: A systematic review. AB - BACKGROUND: Consensus lacks concerning management of ventral hernia in women who are, or might become pregnant. The aim of this systematic review was to examine the risk of recurrence following pre-pregnancy ventral hernia repair, and secondly the prevalence of ventral hernia during pregnancy and the risk of surgical repair pre- and post-partum. DATA SOURCES: PubMed, Embase, CINAHL, Cochrane Library and Web of Science were systematically searched for randomized controlled trials, case-control, cohort studies and larger case-series on ventral (umbilical, epigastric or incisional) hernia repair in relation to pregnancy. CONCLUSIONS: If possible, elective ventral repair should be postponed until after last pregnancy. A non-mesh repair seems appropriate for smaller primary ventral hernia in women who plan future pregnancies. Umbilical hernia during pregnancy seems very rare and seldom requires repair pre- and post-partum. Routine practice of umbilical hernia repair in combination with cesarean section cannot be recommended. PROSPERO: CRD42017073736. PMID- 29798765 TI - Biodegradable-Polymer Drug-Eluting Stent Platforms: The Importance of Long-Term Outcomes. PMID- 29798766 TI - Disease Burden and Clinical Outcomes Following Initial Diagnosis of Critical Limb Ischemia in the Medicare Population. PMID- 29798767 TI - The Long-Term Impact of Post-Procedural Asymmetry and Eccentricity of Bioresorbable Everolimus-Eluting Scaffold and Metallic Everolimus-Eluting Stent on Clinical Outcomes in the ABSORB II Trial. PMID- 29798768 TI - Predictors of Calcium Fracture Derived From Balloon Angioplasty and its Effect on Stent Expansion Assessed by Optical Coherence Tomography. PMID- 29798764 TI - Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve. AB - Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging-based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses. PMID- 29798769 TI - Images in Intervention: Icons. PMID- 29798771 TI - 2-Year Outcomes From the Largest Real-Life Global Registry Investigating Drug Coated Balloon Angioplasty for Femoropopliteal Artery Disease: Time for a Treatment Shift Toward Drug Elution and Minimal Stenting? PMID- 29798772 TI - 1-Year All-Comers Analysis of the Eluvia Drug-Eluting Stent for Long Femoropopliteal Lesions After Suboptimal Angioplasty. AB - OBJECTIVES: The aim of this study was to assess the performance of the fluoropolymer-based paclitaxel-eluting stent (PES) in long femoropopliteal lesions. BACKGROUND: The new-generation fluoropolymer-based PES showed promising outcomes in short femoropopliteal lesions. The main feature of the stent is its controlled and sustained paclitaxel release over 12 months. However, the safety and efficacy of this technology in longer femoropopliteal lesions remain unclear. METHODS: Between March 2016 and March 2017, 62 patients were included in this analysis. Indications for fluoropolymer-based PES deployment were insufficient luminal gain or flow-limiting dissection after plain old balloon angioplasty in a femoropopliteal lesion. Primary patency, freedom from target lesion revascularization, amputation-free survival, and paclitaxel-related adverse events were retrospectively analyzed for up to 1 year of follow-up. RESULTS: Lesions were de novo in 84% of patients. Mean lesion length was 20 +/- 12 cm, and 79% of the lesions (n = 49) were chronic total occlusions. Moderate or severe calcification was present in 42% of the lesions (n = 26). Stent implantation involved the distal superficial femoral artery and the proximal popliteal artery in 76% (n = 47) and 44% (n = 27) of patients, respectively. The Kaplan-Meier estimate of primary patency and freedom from target lesion revascularization was 87%. Amputation-free survival was 100% for patients with claudication (n = 32 [52%]) and 87% in patients with critical limb ischemia (n = 30 [48%]) (hazard ratio: 6.3; 95% confidence interval: 1.25 to 31.54; p = 0.052). Five aneurysm formations of the treated segments (8%) were thought to be attributable to paclitaxel. CONCLUSIONS: The fluoropolymer-based PES showed promising 1-year clinical and angiographic outcomes in real-world long femoropopliteal lesions. The long-term impact of aneurysm formation remains to be further investigated. PMID- 29798773 TI - Paclitaxel-Eluting Stents and Aneurysm Formation, A Worrisome Association. PMID- 29798770 TI - Drug-Coated Balloon Treatment of Femoropopliteal Lesions for Patients With Intermittent Claudication and Ischemic Rest Pain: 2-Year Results From the IN.PACT Global Study. AB - OBJECTIVES: The IN.PACT Global Study is the largest prospective, multicenter, independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and/or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in randomized controlled trials. BACKGROUND: Randomized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter Society Consensus Document II A and B lesions, but there is a need for large scale prospective studies to evaluate a broader range of lesions. METHODS: The IN.PACT Global Study enrolled 1,535 subjects, and 1,406 (1,773 lesions) were included in the pre-defined clinical cohort analysis. Freedom from clinically driven target lesion revascularization was evaluated at 24 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven target vessel revascularization within 24 months. RESULTS: Mean lesion length was 12.1 cm, 35.5% were total occlusions, and 18.0% had in-stent restenosis. Freedom from clinically driven target lesion revascularization at 24 months was 83.3%, the composite safety endpoint was met in 81.7%, the 2-year all-cause mortality rate was 7.0%, and the major target limb amputation rate was 0.7%. Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinically driven target lesion revascularization by 24 months. CONCLUSIONS: This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly designed randomized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment. (IN.PACT Global Clinical Study; NCT01609296). PMID- 29798774 TI - Impact of Optimized Procedure-Related Factors in Drug-Eluting Balloon Angioplasty for Treatment of In-Stent Restenosis. AB - OBJECTIVES: The aim of this study was to investigate the impact of optimizing procedure-related factors during drug-eluting balloon (DEB) angioplasty on clinical outcomes of drug-eluting stent in-stent restenosis (ISR). BACKGROUND: Although DEB angioplasty is recommended as a reasonable option for ISR, recurrent target lesion failure (TLF) still occurs in many patients after DEB angioplasty. METHODS: Consecutive patients with drug-eluting stent ISR treated with DEB (SeQuent Please) were collected from 4 centers in Korea. The primary outcome was 2-year TLF. Procedure-related modifiable independent predictors for TLF and their best cutoff values were determined. RESULTS: In a total of 256 patients (309 lesions), TLF occurred in 52 patients (20.3%). Modifiable independent predictors of TLF among procedure-related factors were residual diameter stenosis after lesion preparation (residual percentage diameter stenosis [%DS]), DEB-to-stent ratio (BSR), and DEB inflation time (Tinflation), whose best cutoff values were 20%, 0.91, and 60 s, respectively. TLF rates were significantly higher in groups with residual %DS >=20% (34.7% vs. 12.5%; adjusted hazard ratio: 2.15; 95% confidence interval: 1.86 to 2.48; p < 0.001), BSR <=0.91 (46.4% vs. 21.9%; adjusted hazard ratio: 2.02; 95% confidence interval: 1.75 to 2.34; p < 0.001), and Tinflation <=60 s (26.2% vs. 14.0%; adjusted hazard ratio: 1.82; 95% confidence interval: 1.36 to 2.45; p < 0.001). When classifying ISR lesions by combination of procedure-related factors, TLF occurred in 8.3% in the fully optimized procedure group (residual %DS <20%, BSR >0.91, and Tinflation >60 s) and 66.7% in the nonoptimized group (residual %DS >=20%, BSR <=0.91, and Tinflation <=60 s) (p < 0.001). CONCLUSIONS: Residual %DS after lesion preparation, BSR, and Tinflation were the only modifiable procedure-related factors in DEB angioplasty. Fully optimized DEB angioplasty with optimal lesion preparation, prolonged inflation, and sufficient dilation may play an important role in reducing TLF after DEB angioplasty. PMID- 29798775 TI - Drug-Eluting Balloon Therapy for In-Stent Restenosis of Drug-Eluting Stents: Choose and Prepare the Appropriate Lesion. PMID- 29798777 TI - Farewell to Drug-Eluting Balloons for In-Stent Restonsis?: Appropriate Technique of Drug-Eluting Balloons Implantation Matters. PMID- 29798778 TI - Comparison of a Novel Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent: 5-Year Outcomes of the Randomized BIOFLOW-II Trial. AB - OBJECTIVES: The authors aimed to compare long-term data of an ultrathin cobalt chromium stent with passive silicon carbide coating and an active biodegradable polymer that releases sirolimus (O-SES) (Orsiro, BIOTRONIK, Bulach, Switzerland) with the durable polymer-based Xience Prime everolimus-eluting stent (X-EES) (Abbott Vascular, Santa Clara, California). BACKGROUND: Biodegradable polymer stents have been developed aiming to overcome long-term detrimental effects of durable polymer stents, ultimately leaving a bare-metal stent in the vessel. METHODS: This multicenter, assessor-blinded trial randomized 452 patients with 505 lesions to either O-SES or X-EES in a 2:1 fashion. Endpoints at 5 years were target lesion failure (TLF), its components, and stent thrombosis. RESULTS: TLF occurred in 10.4% (n = 30) of O-SES patients versus 12.7% (n = 19) of X-EES patients (p = 0.473), overall stent thrombosis occurred in 0.7% (n = 2) versus 2.8% (n = 4) (p = 0.088), and definite stent thrombosis in 0% versus 0.7% (n = 1) (p = 0.341). Post hoc analysis was performed in diabetic patients (n = 128) and vessels <=2.75 mm (n = 259). In diabetic patients, the O-SES group had numerically more target lesion revascularizations (13.5% vs. 4.5%; p = 0.138), but fewer cardiac deaths (1.3% vs. 6.9%; p = 0.089) and stent thrombosis (0% vs. 6.9%; p = 0.039). In small vessels, the O-SES group had a significantly lower 5 year mortality (3.7% vs. 11.3%; p = 0.022). CONCLUSIONS: At 5 years, the biodegradable polymer O-SES demonstrated low TLF rates comparable to the durable polymer X-EES, confirming its long-term safety and performance. Particularly encouraging is the absence of definite stent thrombosis. PMID- 29798779 TI - Subjective perception of paraesthesia of the lower lip after bilateral sagittal split osteotomy at a district general hospital. AB - Our aim was to assess patients' perception of paraesthesia of the lower lip after bilateral sagittal split osteotomy (BSSO) at a district general hospital. Patients who had BSSO between August 2013 and August 2014 (n=46) were asked to score their perception of numbness between 0-10 (0=normal sensation. 10=complete loss of sensation/total numbness) one day postoperatively and then weekly for seven weeks, and at three months, 6 months, and one year. Data was collected on score sheets and by regular contact by telephone. Of the 46 operated on, 31 were female and 15 male. Data were available one year postoperatively for 43 patients. Ten of the 92 sides were reported as feeling normal on day 1 postoperatively, three-quarters as feeling normal at six months, and 79 at one year. On multivariate analysis there was no significant difference in postoperative sensation at one year between sides operated on by the registrar (left) and consultant (right) operated (p=0.76). Our results compared favourably with the limited data available in similarly designed studies. PMID- 29798776 TI - 3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents. AB - OBJECTIVES: This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). BACKGROUND: Treatment of patients with DES-ISR remains a challenge. METHODS: The RIBS IV (Restenosis Intra Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. RESULTS: A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 +/- 0.7 mm vs. 1.80 +/- 0.6 mm; p < 0.01). Three-year clinical follow-up was obtained in all enrolled patients (100%). The combined clinical outcome measure of cardiac death, myocardial infarction and target lesion revascularization was significantly reduced in the EES arm (19 [12.3%] vs. 31 [20.1%]; p = 0.04; hazard ratio: 0.57 [95% confidence interval: 0.34 to 0.96]), driven by a lower need for target lesion revascularization (11 [7.1%] vs. 24 [15.6%]; p = 0.015; hazard ratio: 0.43 [95% confidence interval: 0.21 to 0.87]). The need for "late" (>1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. CONCLUSIONS: The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940). PMID- 29798780 TI - [Problems encountered by hospital pharmacists with information systems: Analysis of exchanges within social networks]. AB - OBJECTIVE: The development of information systems in French hospitals is mandatory. The aim of this work was to analyze the content of exchanges carried out within social networks, dealing with problems encountered with hospital pharmacies information systems. METHODS: Messages exchanged via the mailing list of the Association pour le Digital et l'Information en Pharmacie and abstracts of communications presented at hospital pharmacists trade union congresses were analyzed. Those referring to information systems used in hospital pharmacies were selected. RESULTS: From March 2015 to June 2016, 122 e-mails sent by 80 pharmacists concerned information systems. From 2002 to 2016, 45 abstracts dealt with this topic. Problems most often addressed in these 167 documents were "parameterization and/or functionalities" (n=116), interfaces and complexity of the hospital information systems (n=52), relationship with health information technologies vendors and poor reactivity (n=32), additional workload (n=32), ergonomics (n=30), insufficient user training (n=22). These problems are interdependent, lead to errors and in order to mitigate their consequences, they compel pharmacy professionals to divert a significant amount of working hours to the detriment of pharmaceutical care and dispensing and preparing drugs. CONCLUSION: Hospital pharmacists are faced with many problems of insecurity and inefficiency generated by information systems. Researches are warranted to determine their cost, specify their deleterious effects on care and identify the safest information systems. PMID- 29798781 TI - On the dimorphism and the pressure-temperature state diagram of racemic m nisoldipine, a dihydropyridine calcium ion antagonist. AB - The pressure-temperature phase diagram of the dimorphism of racemic m-nisoldipine is constructed using temperatures and enthalpies of fusion of forms A and B. At ordinary pressure, the transition from form B to form A is found to occur around 192K, which indicates that these polymorphs are enantiotropically related and that form A is stable at room temperature. Nevertheless, the phase relationship turns to be monotropic when pressures become greater than about 100MPa, which indicates that form B becomes the sole stable phase. PMID- 29798782 TI - Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy. AB - SCN5A gene encodes the pore-forming ion-conducting alpha-subunit of the cardiac sodium channel (Nav1.5), which is responsible for the initiation and propagation of action potentials and thereby determines cardiac excitability and conduction of electrical stimuli through the heart. The importance of Nav1.5 for normal cardiac electricity is reflected by various disease entities that can be caused by mutations in SCN5A. Gain-of-function mutations in SCN5A lead to more sodium influx into cardiomyocytes through aberrant channel gating and cause long QT syndrome, a primary electrical disease of the heart. Loss-of-function mutations in SCN5A lead to lower expression levels of SCN5A or production of defective Nav1.5 proteins and cause Brugada syndrome, an electrical disease with minor structural changes in the heart. In addition, both loss- and gain-of-function mutations may cause dilated cardiomyopathy, which is an arrhythmogenic disease with gross structural defects of the left ventricle (and sometimes both ventricles). Other SCN5A-related diseases are multifocal ectopic premature Purkinje-related complexes (gain-of-function mutations), isolated cardiac conduction defect (loss-of-function mutations), sick sinus syndrome (loss-of function mutations), atrial fibrillation (loss-of-function or gain-of-function mutations), and overlap syndromes (mutations with both loss-of-function and gain of-function effects). Growing insights into the role of SCN5A in health and disease has enabled clinicians to lay out gene-specific risk stratification schemes and mutation-specific diagnostic and therapeutic strategies in the management of patients with a SCN5A mutation. This review summarizes currently available knowledge about the pathophysiological mechanisms of SCN5A mutations and describes how this knowledge can be used to manage patients suffering from potentially lethal cardiac diseases. PMID- 29798783 TI - A Prospective Randomized Trial of Apixaban Dosing During Atrial Fibrillation Ablation: The AEIOU Trial. AB - OBJECTIVES: This study sought to determine whether uninterrupted apixaban would have similar rates of bleeding and thromboembolic events as does minimally interrupted apixaban at the time of atrial fibrillation (AF) ablation and to compare those results with rates in historical patients treated with uninterrupted warfarin. BACKGROUND: The safety, efficacy, and optimal dosing regimen for apixaban at the time of AF ablation are uncertain. METHODS: This prospective, multicenter clinical trial enrolled 306 patients undergoing catheter ablation for nonvalvular AF and randomized 300 to uninterrupted versus minimally interrupted (holding 1 dose) periprocedural apixaban. A retrospective cohort of patients treated with uninterrupted warfarin at the same centers was matched to the apixaban-treated subjects for comparison. Endpoints included clinically significant bleeding, major bleeding, and nonhemorrhagic stroke or systemic embolism (SE) from the time of ablation through 30 days. RESULTS: There were no stroke or SE events. Clinically significant bleeding occurred in 11.3% of 150 evaluable patients on uninterrupted apixaban and 9.7% of 145 evaluable patients on interrupted apixaban (risk difference: 1.7% [95% confidence interval: -5.5% to 8.8%]; p = NS). Rates of major bleeding were 1.3% with uninterrupted apixaban, and 2.1% with interrupted (risk difference: -0.7%; p = NS). The rates of clinically significant and major bleeding were similar for all apixaban patients combined (10.5% and 1.7%), compared with the matched warfarin group (9.8% and 1.4%). CONCLUSIONS: Both uninterrupted and minimally interrupted apixaban at the time of AF ablation were associated with a very low rate of thromboembolic events, and rates of both major (<2%) and clinically significant bleeding were similar to uninterrupted warfarin. (Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation [AEIOU]; NCT02608099). PMID- 29798784 TI - Periablation Anticoagulation: Translating Research Into Clinical Practice. PMID- 29798785 TI - Uninterrupted Direct Oral Anticoagulant and Warfarin Administration in Elderly Patients Undergoing Catheter Ablation for Atrial Fibrillation: A Comparison With Younger Patients. AB - OBJECTIVES: The goal of this study was to evaluate the efficacy and safety of uninterrupted direct oral anticoagulant (DOAC) use and uninterrupted warfarin administration in elderly patients undergoing catheter ablation for atrial fibrillation (AF). BACKGROUND: There is limited knowledge regarding the uninterrupted use of oral anticoagulant agents in elderly patients undergoing catheter ablation for AF. METHODS: This retrospective study included 2,164 patients (n = 325 >=75 years of age and n = 1,839 <75 years of age) who underwent catheter ablation for AF. All the patients received uninterrupted oral anticoagulant agents during the procedure. We investigated the occurrences of periprocedural events and compared these between the DOAC and warfarin groups of the elderly and younger groups. RESULTS: Major bleeding events (3.1% vs. 1.3%; p = 0.023) and minor bleeding events (9.2% vs. 5.0%; p = 0.002), except for thromboembolic events (0% vs. 0.8%; p = 0.248), were significantly higher in the elderly group than in the younger group. No significant differences in thromboembolic and bleeding events were found between the DOAC and warfarin groups of both the elderly and younger groups. Adverse complications did not differ between the groups after adjustment using propensity score matching analysis. Multivariate analysis revealed that lower body weight (odds ratio: 0.96; p = 0.010) and antiplatelet drug use (odds ratio: 2.21; p = 0.039) were independent predictors of adverse events in the elderly group. CONCLUSIONS: The periprocedural bleeding risk during the use of uninterrupted oral anticoagulants was higher in the elderly group than in the younger group. This area needs more attention for these patients in whom caution is required. PMID- 29798786 TI - Safety and Efficacy of Uninterrupted Direct Oral Anticoagulant Administration in Elderly Patients Undergoing Catheter Ablation of Atrial Fibrillation. PMID- 29798788 TI - Sex and Stroke Risk in Atrial Fibrillation: More Work to Be Done. PMID- 29798787 TI - Comparing Management and Outcomes in Men and Women With Nonvalvular Atrial Fibrillation: Data From a Population-Based Cohort. AB - OBJECTIVES: This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF). BACKGROUND: There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF. METHODS: The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding. RESULTS: The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Sex did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p < 0.001); however, women had a significantly lower adjusted mortality risk (HR: 0.78; 95% CI: 0.71 to 0.86). Women had lower risk of intracranial hemorrhage (HR: 0.81; 95% CI: 0.76 to 0.87) and major gastrointestinal bleeding (HR: 0.78; 95% CI: 0.70 to 0.87). CONCLUSIONS: Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors. PMID- 29798789 TI - Burden of Atrial Fibrillation-Associated Ischemic Stroke in the United States. AB - OBJECTIVES: This study aimed to investigate whether the excess morbidity and mortality of atrial fibrillation (AF)-related stroke persists in the contemporary era. BACKGROUND: Acute ischemic stroke (AIS) in patients with AF is associated with worse outcomes than in patients without AF. Stroke prevention strategies in patients with AF have improved over the last decade and AIS-related mortality overall has also declined. METHODS: Patients >=18 years of age who were admitted with AIS between 2003 and 2014 were identified in the National Inpatient Sample. The study compared crude and propensity score-matched in-hospital morbidity and mortality, cost, length of stay, and discharge dispositions between patients with and without AF. RESULTS: A total of 930,010 patients were admitted with AIS, and 18.2% of these patients had AF. The prevalence of AF in these patients increased from 16.4% in 2003 to 20.4% in 2014, with the greatest increase observed in white and older patients. Propensity score matching attained 2 pairs of 125,203 patients with AIS with and without AF. In these matched cohorts, the mortality rate was higher in patients with AF (9.9% vs. 6.1%; p < 0.001). Ischemic stroke in patients with AF was also associated with higher incidences of acute kidney injury, bleeding and infectious complications, and severe disability. Hospital length of stay was significantly longer, and cost of care was 20% higher in patients with AF. CONCLUSIONS: The prevalence of AF in AIS patients continued to rise, particularly in white and older patients. Despite the improvement in AIS related morality overall, the differential negative impact of AF on the morbidity, mortality, and cost of AIS was steady over the study's 12-year period. PMID- 29798790 TI - The Clinical Benefits and Mortality Reduction Associated With Catheter Ablation in Subjects With Atrial Fibrillation: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: This study sought to compare the efficacy and safety of catheter ablation (CA) with those of medical therapy (MT) for the treatment of atrial fibrillation (AF). BACKGROUND: The preferred therapeutic strategy for subjects with AF remains unclear. METHODS: A total of 17 randomized controlled trials were selected using Medline, EMBASE, and CENTRAL (September 1998 to 2 February 2018). The analysis was stratified at the trial level according to the following: 1) patients with AF and heart failure (HF); and 2) patients with AF without HF. RESULTS: A total of 2,272 patients with AF (775 patients with HF and 1,497 patients without HF) participated in this analysis. In patients with HF, CA was associated with significant relative risk reduction in all-cause mortality (risk ratio [RR]: 0.52; 95% confidence interval [CI]: 0.36 to 0.76; p < 0.001; I2 = 0), recurrent atrial arrhythmia (RR: 0.44; 95% CI: 0.31 to 0.61; p <0.001; I2 = 56), and cardiac hospitalization (RR: 0.63; 95% CI: 0.46 to 0.87; p = 0.01; I2 = 43) compared with MT. Conversely, in patients without HF, CA had no beneficial effect on the risk of all-cause mortality compared with MT (RR: 0.88, 95% CI: 0.29 to 2.61; p = 0.81; I2 = 0). However, CA reduced the risk of recurrent atrial arrhythmia (RR: 0.40; 95% CI: 0.31 to 0.52; p < 0.001; I2 = 73) and cardiac hospitalization (RR: 0.32; 95% CI: 0.23 to 0.45; p < 0.001; I2 = 0) in patients without HF. CONCLUSIONS: This meta-analysis suggests that although CA reduced the risk of cardiac hospitalization and recurrent atrial arrhythmia both in subjects with HF and in subjects without HF, the reduction in all-cause mortality was limited to subjects with HF only. PMID- 29798791 TI - Catheter Ablation: First-Line Therapy for Atrial Fibrillation in Systolic Heart Failure? PMID- 29798792 TI - Medical and Interventional Outcomes in Pediatric Lone Atrial Fibrillation. AB - OBJECTIVES: The goal of this study was to describe the clinical characteristics of pediatric patients with lone atrial fibrillation (LAF) and their treatment outcomes. The authors focused on patients who underwent ablation and compared the recurrence after ablation of supraventricular tachycardia substrates as presumed triggers versus pulmonary vein isolation (PVI). BACKGROUND: LAF in pediatrics is rare, and outcomes remain poorly defined. Current guidelines on ablation are based on a few small studies, and we present outcomes from the largest cohort of patients after ablation. METHODS: This retrospective review included patients <=21 years of age diagnosed with LAF from 2004 to 2015. Relevant clinical data, including recurrence rates after treatment, were tracked and analyzed with a focus on patients who underwent ablation procedures. RESULTS: Sixty-two patients were identified with LAF; 88% were male, and 63% were athletes. Of the 33 patients taking antiarrhythmic medication, 20 (61%) experienced recurrence. Overall, 16 patients (26%) underwent ablation: PVI in 10 (62.5%), ablation of an accessory pathway in 3 (19%), and modification of the slow atrioventricular nodal pathway in 3 (19%). One-half of patients who underwent PVI experienced documented recurrence. Of those who solely underwent supraventricular tachycardia substrate ablation, one-half also had symptomatic or documented recurrence. CONCLUSIONS: Ablation recurrence within this pediatric cohort was higher than expected. These recurrence rates may be demonstrative of the technical challenge of pediatric ablation compared with adult counterparts, characteristics of these patients such as athletic conditioning, or inherent differences in their atrial tissue, rendering it more refractory to substrate modification. PMID- 29798793 TI - Delirium Cordis: An Arrhythmia at the Intersection of Pediatric and Adult Electrophysiology. PMID- 29798794 TI - Impact of Body Mass Index on Safety and Efficacy of the Subcutaneous Implantable Cardioverter-Defibrillator. AB - OBJECTIVES: This study determined whether obesity increased the risk of failed shocks and complications among subcutaneous implantable cardioverter defibrillator (S-ICD) recipients. BACKGROUND: The S-ICD is an established treatment for patients at high risk for ventricular arrhythmias. Obesity may increase the transvenous defibrillation threshold and the rate of complications. METHODS: We analyzed data from the 321 patients enrolled in the S-ICD Investigational Device Exemption (IDE) study. They were categorized into 3 body mass index (BMI) groups: <25 kg/m2 (underweight and normal), 25 to 30 kg/m2 (overweight), and >30 kg/m2 (obese). Patients underwent implantation followed by defibrillation testing at 65 J. Chronic defibrillation testing was repeated >150 days post implantation in a subset of patients. RESULTS: Seventy-nine patients had BMI <25 kg/m2, 105 had BMI 25 to 30 kg/m2, and 137 had BMI >30 kg/m2. A failed first shock of any kind occurred in 52 patients, including 41 patients during implant defibrillation testing, 11 patients during chronic defibrillation testing, and 5 patients during spontaneous ventricular arrhythmias. The rate of failed first shocks during implant defibrillation testing increased across BMI categories (5.1% among underweight and normal patients, 13.3% among overweight patients, and 16.9% among obese patients; p = 0.04). Among obese patients, shock impedance was higher during failed first shocks than successful first shocks (103.5 ohms vs. 84.6 ohms; p = 0.001). The rate of failed first shocks during chronic defibrillation testing and spontaneous ventricular arrhythmias did not significantly differ among BMI groups, nor did the rate of complications. Of the 8 underweight patients, there were no failed shocks or complications. CONCLUSIONS: Obese patients are at increased risk of failed first S-ICD shocks during defibrillation testing. Whether this can be overcome by optimal implantation techniques remains unknown. Rates of complications were not increased among obese patients. PMID- 29798796 TI - Defining an Isthmus for the Cost Effectiveness of Catheter Ablation for Ventricular Tachycardia Associated With Prior Myocardial Infarction. PMID- 29798795 TI - Cost Effectiveness of Ventricular Tachycardia Ablation Versus Escalation of Antiarrhythmic Drug Therapy: The VANISH Trial. AB - OBJECTIVES: This analysis uses the data from the randomized controlled trial to assess the cost effectiveness of catheter ablation (n = 132) versus escalated antiarrhythmic therapy (n = 127). BACKGROUND: For survivors of myocardial infarction with implantable cardioverter-defibrillator shocks despite antiarrhythmic drugs, the VANISH (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial demonstrated improved clinical outcomes with catheter ablation compared with more aggressive antiarrhythmic pharmacotherapy. METHODS: Health care resource use and quality-of-life data were used to determine the cost effectiveness of catheter ablation. Published references were used to estimate costs (in 2015 Canadian dollars). The analysis was over 3 years, with a 5% discount rate. Adjustment was made for censoring and baseline utilities. RESULTS: Ablation resulted in greater quality-adjusted life-years (QALYs) than escalated drug therapy did (1.63 vs. 1.49; difference: 0.14; 95% confidence interval [CI]: -0.20 to 0.46) and higher cost ($65,126 vs. $60,269; difference: $4,857; 95% CI: -$19,757 to $27,106); with an incremental cost per QALY gained for ablation versus escalated drug therapy of $34,057 primarily due to the initial costs of ablation, which were partially offset by the costs of subsequent ablations and adverse outcomes in the escalated drug therapy arm. For patients with amiodarone-refractory ventricular tachycardia, ablation dominated escalated drug therapy, with greater QALYs (1.48 vs. 1.26; difference: 0.22; 95% CI: -0.19 to 0.59) and lower costs ($67,614 vs. $68,383; difference: -$769; 95% CI: -$35,330 to $27,092). For those with sotalol refractory ventricular tachycardia, ablation resulted in similar QALYs (1.90 vs. 1.90; difference: -0.00; 95% CI: -0.59 to 0.62) and higher costs ($60,455 vs. $45,033; difference: $15,422; 95% CI: -$10,968 to $48,555). CONCLUSIONS: For the total trial population, results are suggestive that ablation is cost effective compared with escalation of drug therapy. This result was only manifest for the subgroup of patients whose qualifying arrhythmia occurred despite amiodarone. PMID- 29798797 TI - Change in Left Ventricular Ejection Fraction Following First Myocardial Infarction and Outcome. AB - OBJECTIVES: This study hypothesizes that a lack of left ventricular ejection fraction (LVEF) recovery after myocardial infarction (MI) would be associated with a poor outcome. BACKGROUND: A reduced LVEF early after MI identifies patients at risk of adverse outcomes. Whether the change in LVEF in the weeks to months following MI provides additional information on prognosis is less certain. METHODS: Change in LVEF between the early (2 to 7 days) and later (2 to 12 weeks) post-MI periods in patients with a first MI was assessed in 3 independent cohorts (REFINE [Risk Estimation Following Infarction Noninvasive Evaluation]; CARISMA [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction]; ISAR [Improved Stratification of Autonomy Regulation]). Patients were categorized as having no recovery (Delta <=0%), a modest increase (Delta 1% to 9%), or a large increase (Delta >=10%) in LVEF. The relationship between change in LVEF and risk of sudden cardiac arrest (SCA) and all-cause mortality were assessed in Cox multivariable models. RESULTS: In REFINE, patients with no LVEF recovery had a higher risk of sudden cardiac arrest (hazard ratio: 5.8; 95% confidence interval: 2.1 to 16.6; p = 0.001) and death (hazard ratio: 3.9; 95% confidence interval: 1.5 to 10.1; p < 0.001), independent of revascularization, baseline LVEF, and medical therapy compared with patients with recovery. Similar findings were observed in the other cohorts. LVEF reassessments beyond 6 weeks post-MI were more predictive of outcome than were earlier reassessments. CONCLUSIONS: The degree of LVEF recovery after a first MI provides important prognostic information. Patients with no recovery in LVEF after MI are at high risk of sudden cardiac arrest events and death. PMID- 29798798 TI - If We Knew Then What We Know Now: Change in Ejection Fraction Post-Myocardial Infarction and Outcome. PMID- 29798800 TI - Estimating Cardiac Sympathetic Activity From Subcutaneous Nerve Recordings: More Than Skin Deep? PMID- 29798799 TI - Effects of Stellate Ganglion Cryoablation on Subcutaneous Nerve Activity and Atrial Tachyarrhythmias in a Canine Model of Pacing-Induced Heart Failure. AB - OBJECTIVES: This study aimed to test the hypothesis that subcutaneous nerve activity (SCNA) can adequately estimate the cardiac sympathetic tone and the effects of cryoablation of the stellate ganglion in dogs with pacing-induced heart failure (HF). BACKGROUND: Recording of SCNA is a new method to estimate sympathetic tone in dogs. HF is known to increase sympathetic tone and atrial arrhythmias. METHODS: Twelve dogs with pacing-induced HF were studied using implanted radiotransmitters to record the stellate ganglia nerve activity (SGNA), vagal nerve activity, and SCNA. Of these, 6 dogs (ablation group) underwent bilateral stellate ganglia cryoablation before the rapid ventricular pacing; the remaining 6 dogs (control group) had rapid ventricular pacing only. In both groups, SCNA was compared with SGNA and the occurrence of arrhythmias. RESULTS: SCNA invariably increased before the 360 identified atrial tachyarrhythmia episodes in the 6 control dogs before and after HF induction. SCNA and SGNA correlated in all dogs with an average correlation coefficient of 0.64 (95% confidence interval: 0.58 to 0.70). Cryoablation of bilateral stellate ganglia significantly reduced SCNA from 0.34 +/- 0.033 MUV to 0.25 +/- 0.028 MUV (p = 0.03) and eliminated all atrial tachyarrhythmias. CONCLUSIONS: SCNA can be used to estimate cardiac sympathetic tone in dogs with pacing-induced HF. Cryoablation of the stellate ganglia reduced SCNA and arrhythmia vulnerability. PMID- 29798802 TI - Sinoventricular Conduction in the Setting of Severe Hyperkalemia. PMID- 29798801 TI - A Unique Emergency Maneuver and Rescue During Left Atrial Appendage Occlusion Device-Related Cardiac Perforation. PMID- 29798803 TI - Impact of Evolving Comorbidities on Outcomes After Catheter Ablation of Atrial Fibrillation in the United States Between 2003 and 2013. PMID- 29798804 TI - Hyphenation of capillary electrophoresis to inductively coupled plasma mass spectrometry with a modified coaxial sheath-flow interface. AB - Capillary electrophoretic analyses benefit significantly from hyphenation to mass spectrometric techniques. While the coupling to ESI-MS is routinely performed, for example by using a coaxial sheath-flow interface, hyphenating it to inductively coupled plasma mass spectrometry is more technically challenging. We use a commercially available coaxial sheath-flow interface (CSFI) and a simple PTFE-based end-cap for easy, inexpensive CE-ICP-MS hyphenation with improved sensitivity and analytical performance compared to commercially available interfaces. We have optimized key nebulizer parameters such as capillary position, sheath liquid flow rate, and carrier gas flow rate, and compared the CSFI with a commercially available interface. In a set of proof-of-principle experiments employing the anticancer agent cisplatin it was demonstrated that the signal to noise response and sensitivity were considerably improved leading to detection limits for 195Pt of 0.08 MUM. PMID- 29798806 TI - Magnetic molecularly imprinted polymer nanoparticles for simultaneous extraction and determination of 6-mercaptopurine and its active metabolite thioguanine in human plasma. AB - Cytotoxic drugs used in cancer chemotherapy require the continuous monitoring of their plasma concentration levels for dose adjustment purposes. Such condition necessitates the presence of a sensitive technique for accurate extraction and determination of these drugs together with their active metabolites. In this study a novel solid phase extraction technique using magnetic molecularly imprinted nanoparticles (MMI-SPE) is combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) to extract and determine the anti-leukemic agent; 6 mercaptopurine (6-MP) and its active metabolite thioguanine (TG) in human plasma. The magnetic molecularly imprinted nanoparticles (Fe3O4@MIP NPs) were synthesized via precipitation polymerization technique and were characterized using different characterization methods A computational approach was adopted to help in the choice of the monomer used in the fabrication process. The Fe3O4@MIPs NPs possessed a highly improved imprinting efficiency, fast adsorption kinetics following 2nd order kinetics and good adsorption capacity of 1.0 mg/g. The presented MMI-SPE provided the optimum approach in comparison to other reported ones to achieve good extraction recovery and matrix effect of trace levels of 6 MP and TG from plasma. Chromatographic separation was carried out using a validated LC-MS/MS assay and recovery, matrix effect and process efficiency were evaluated. Recovery of 6-MP and TG was in the range of 85.94-103.03%, while, matrix effect showed a mean percentage recovery of 85.94-97.62% and process efficiency of 85.54-96.18%. The proposed extraction technique is simple, effective and can be applicable to the extraction and analysis of other pharmaceutical compounds in complex matrices for therapeutic drug monitoring applications. PMID- 29798805 TI - Screening and identification of ligand-protein interactions using functionalized heat shock protein 90-fluorescent mesoporous silica-indium phosphide/zinc sulfide quantum dot nanocomposites. AB - Currently, nanosphere-based ligand fishing cannot be accomplished with imaging processing, although this step is important for real-time identification. Herein, a ligand fishing technique combined with real-time imaging is presented for the identification of ligands for heat shock protein 90alpha (Hsp 90alpha) from a complex matrix, Alisma plantago-aquatica Linn. crude extract, using Hsp 90alpha functionalized mesoporous silica nanoparticle (MSN)-InP/ZnS quantum dot (QD) nanocomposites as a support material. Twenty ligands for Hsp 90alpha were screened, and their structures were identified by mass spectrometry. The activities of the ligands were verified by real-time imaging of cells apoptotic morphological changes. Quantitative analysis showed that Alisma plantago-aquatica Linn contained 8.19MUg/g Alisol F, which regarded as one typical component of Alisma plantago-aquatica Linn, and the extraction ratio of Alisol F was 76.2%. The precision for five replicate measurements was 7.0% (RSD). The prepared nanocomposites were also used to screen proteins from a mixture of cellular extracts, and five proteins from HeLa cells were identified as potential client proteins of Hsp 90alpha. PMID- 29798807 TI - Methodology to determine the extent of anaerobic digestion, composting and CH4 oxidation in a landfill environment. AB - An examination of the processes contributing to the production of landfill greenhouse gas (GHG) emissions is required, as the actual level to which waste degrades anaerobically and aerobically beneath covers has not been differentiated. This paper presents a methodology to distinguish between the rate of anaerobic digestion (rAD), composting (rCOM) and CH4 oxidation (rOX) in a landfill environment, by means of a system of mass balances developed for molecular species (CH4, CO2) and stable carbon isotopes (delta13C-CO2 and delta13C-CH4). The technique was applied at two sampling locations on a sloped area of landfill. Four sampling rounds were performed over an 18 month period after a 1.0 m layer of fresh waste and 30-50 cm of silty clay loam had been placed over the area. Static chambers were used to measure the flux of the molecular and isotope species at the surface and soil gas probes were used to collect gas samples at depths of approximately 0.5, 1.0 and 1.5 m. Mass balances were based on the surface flux and the concentration of the molecular and isotopic species at the deepest sampling depth. The sensitivity of calculated rates was considered by randomly varying stoichiometric and isotopic parameters by +/-5% to generate at least 500 calculations of rOX, rAD and rCOM for each location in each sampling round. The resulting average value of rAD and rCOM indicated anaerobic digestion and composting were equally dominant at both locations. Average values of rCOM: ranged from 9.8 to 44.5 g CO2 m-2 d-1 over the four sampling rounds, declining monotonically at one site and rising then falling at the other. Average values of rAD: ranged from 10.6 to 45.3 g CO2 m-2 d-1. Although the highest average rAD value occurred in the initial sampling round, all subsequent rAD values fell between 10 and 20 g CO2 m-2 d-1. rOX had the smallest activity contribution at both sites, with averages ranging from 1.6 to 8.6 g CO2 m-2 d-1. This study has demonstrated that for an interim cover, composting and anaerobic digestion of shallow landfill waste can occur simultaneously. PMID- 29798808 TI - Management of placenta percreta with temporary balloon occlusion of the internal iliac arteries. PMID- 29798809 TI - Molecular Testing Turnaround Time in Non-Small-Cell Lung Cancer: Monitoring a Moving Target. PMID- 29798810 TI - Unusual cause of left ventricular dysfunction in a child. AB - Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery is a rare congenital heart disease and a cause of myocardial ischemia during childhood. Most undiagnosed cases die in the first year of life as an extensive collateral network is essential for survival. The diagnosis requires a high index of clinical suspicion. The authors present the case of an 8-year-old black asymptomatic child referred from Cape Verde Island in order to clarify left ventricular dilatation and dysfunction with systo-diastolic turbulent flows observed at the interventricular septum. At the age of 3 months, she was diagnosed with heart failure, in the context of showing dilated cardiomyopathy. She was managed and clinically improved with anticongestive therapy, which she was still taking at the time of admission to our Center. The echocardiogram findings suggested Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery and the diagnosis was confirmed by computerized angiotomography and cardiac catheterization. The patient was successfully submitted to direct implantation of the left coronary artery into the aorta, allowing the creation of a double coronary perfusion system. This case illustrates an unusual presentation of a rare pathology that survived without a diagnosis after the first year of life. It also reinforces the importance of multimodality image screening in these cases. PMID- 29798811 TI - Are defibrillators less useful in patients with non-ischemic heart disease? AB - INTRODUCTION AND OBJECTIVE: The benefits of implanted defibrillators in patients with ischemic heart disease (IHD) are well known. However, the evidence is less robust in patients with non-ischemic heart disease (non-IHD). We aimed to determine whether patients with non-IHD have a similar incidence of appropriate shocks and all-cause mortality compared to those with IHD. METHODS: In a retrospective single-center study we analyzed all patients with implantable cardioverter-defibrillators or cardiac resynchronization therapy-defibrillators implanted for primary prevention between 2004 and 2014. The population was divided into two groups: patients with IHD and patients with non-IHD. The composite endpoint was appropriate shock and all-cause mortality. RESULTS: Two hundred and eighty-one patients were studied, of whom 187 (66%) had IHD. Patients with IHD were older, more frequently male and with more cardiovascular risk factors. Mean follow-up was 55+/-42 months. Thirty-four patients (18%) with IHD and 20 patients (21%) with non-IHD had an appropriate shock (p=0.64). Eighty-nine patients (47%) with IHD and 36 (38%) with non-IHD died during follow-up (p=0.19). The rate of shocks or death over time was similar in patients with IHD and non IHD according to Kaplan-Meier survival curve analysis (log-rank p=0.10). CONCLUSION: In this population, there were no differences in appropriate shocks or all-cause mortality in the two groups. PMID- 29798812 TI - Concurrency of partnerships, consistency with data, and control of sexually transmitted infections. AB - Sexually transmitted infections (STIs) are a globally increasing public health problem. Mathematical models, carefully matched to available epidemiological and behavioural data, have an important role to play in predicting the action of control measures. Here, we explore the effect of concurrent sexual partnerships on the control of a generic STI with susceptible-infected-susceptible dynamics. Concurrency refers to being in more than one sexual partnership at the same time, and is difficult to measure accurately. We assess the impact of concurrency through the development of three nested pair-formation models: one where infection can only be transmitted via stable sexual partnerships, one where infection can also be transmitted via casual partnerships between single individuals, and one where those individuals in stable partnerships can also acquire infection from casual partnerships. For each model, we include the action of vaccination before sexual debut to inform about the ability to control. As expected, for a fixed transmission rate, concurrency increases both the endemic prevalence of infection and critical level of vaccination required to eliminate the disease significantly. However, when the transmission rate is scaled to maintain a fixed endemic prevalence across models, concurrency has a far smaller impact upon the critical level of vaccination required. Further, when we also constrain the models to have a fixed number of new partnerships over time (both long-term and casual), then increasing concurrency can slightly decrease the critical level of vaccination. These results highlight that accurate measures and models of concurrency may not always be needed for reliable forecasts when models are closely matched to prevalence data. We find that, while increases in concurrency within a population are likely to generate public-health problems, the inclusion of concurrency may be unnecessary when constructing models to determine the efficacy of the control of STIs by vaccination. PMID- 29798813 TI - The influence of early intervention, informal support and the family environment on trajectories of competence for fathers raising children with developmental disabilities. AB - BACKGROUND: Scant research disentangles the relationship between parenting competence, early intervention (EI) services, the family environment and informal support among fathers of children with developmental disabilities. AIMS: (1) To determine the trajectory of parental competence for fathers of children with DD from age 3 to age 15. (2) Controlling for child and family characteristics, determine the main effects of the family environment, informal support, and EI services on paternal competence when their child with a developmental disability was age 3. (3) To determine whether there were lasting effects of the family environment, informal support, and the EI service system on differences in paternal competence over time. METHODS: This study used multilevel modeling to analyze longitudinal data from 93 American fathers from the Early Intervention Collaborative Study. RESULTS: There was no significant change over time in paternal competence after controlling for various covariates. Fathers who initially reported low levels of competence when their child was three reported continuously lower competence over time. Family relationships, positive supports, and perceived helpfulness of home visits were significant predictors of paternal competence at age three. CONCLUSION: Implications for programs and policy include developing and adopting rigorous ways to measure and carefully monitor service provision, including assessments of paternal competence, family relationships and informal supports at the start of early intervention, and fostering continuous collaborations between providers, researchers and clinicians to address challenges in data collection. PMID- 29798814 TI - [Safety and efficacy of the use of eltrombopag in a case of severe acquired bone marrow aplasia]. PMID- 29798815 TI - Development of a Model to Predict Invasiveness in Ductal Carcinoma In Situ Diagnosed by Percutaneous Biopsy-Original Study and Critical Evaluation of the Literature. AB - BACKGROUND: Approximately 30% of ductal carcinoma in situ (DCIS) cases have an invasive component discovered on the final analysis that could affect surgical management. The aims of the present study were to determine the risk factors associated with the underestimation of DCIS and to develop a model to predict the probability of invasiveness. MATERIALS AND METHODS: A retrospective analysis was performed on the data for all patients with a diagnosis of DCIS found by percutaneous biopsy from January 2008 to February 2016. Thirteen potential predictors of invasiveness were examined. The statistical analysis of the present study was improved using Nagelkerke's R2, the area under the receiving operating characteristic (AUC) curve, and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Of 354 biopsy specimens deemed to be DCIS on initial biopsy, 100 (28.2%) were recategorized as invasive carcinoma after surgery. On multivariate analysis, the strongest predictors of invasiveness were comedonecrosis, size on mammography, suspected microinvasion, histologic grade, and younger patient age. The model had a good discriminative ability, with an AUC of 0.764. The overall performance of the model was fair, with a Nagelkerke's R2 of 40.9%. A separate analysis performed on 274 specimens obtained through vacuum-assisted biopsy revealed different variables were associated with underestimation; however, a similar AUC (0.743) and Nagelkerke's R2 (45.7%) were obtained. CONCLUSION: Our model had the best AUC for predicting DCIS invasiveness reported to date. However, further statistical analysis showed only a fair overall performance. The currently known clinical, radiographic, and pathologic features might be insufficient to identify which patients with DCIS have underestimated disease. PMID- 29798817 TI - Reinforcement with EndoGIATM to Prevent Blow-out of the Aortic Stump. PMID- 29798816 TI - The function of the heart is not obvious. AB - It is widely believed that the function of the heart is obviously to pump blood. I argue here that it is not. The definition, presentation, and pathophysiological explanation of heart failure, as well as the measurement of cardiac dysfunction, are not as might be expected if the function of the heart was simply to pump blood. Far from being obvious, many central features of heart failure are still being investigated. This has important implications for philosophical debates about health and disease. According to naturalists like Christopher Boorse, medical practice is founded on a well-established body of physiological knowledge, which provides the one true account of the biological function of organs. On this naturalistic view, there should only be one account of the pathophysiology of heart failure in use in medical practice. This account of the pathophysiology of heart failure should be well-established, as opposed to uncertain. Medics should use this physiological knowledge to inform their clinical practice, and not vice versa. Clinical considerations, such as whether patients respond to therapy, should not inform debates about what the pathophysiology of heart failure is. I will show this is not the case. The handling of knowledge of the biological function of the heart in medical practice differs substantially from Boorse's account. PMID- 29798818 TI - Remote organ failure in acute kidney injury. AB - Despite supportive care with renal replacement therapy, acute kidney injury (AKI) remains linked with increased short and long-term mortality, not just because of renal failure but also because of accompanying remote organ dysfunction. Increasing evidence from animal studies suggests that numerous factors contribute both to the development of AKI and the impairment of various vital organs, including pro-inflammatory cytokine expression, leukocyte infiltration, vascular permeability changes, ion channel derangement, oxidative stress, and cell apoptosis. Human studies have reported that AKI with concomitant multi-organ dysfunction is associated with a high death rate. We propose that persistent organ dysfunction after AKI can be considered in relation to three proposed mechanisms (1) classical uremic stress and its associated sequelae (2) systemic inflammation as a consequence of kidney injury (3) treatment-related effects. Using this framework, we discuss the known pathways through which AKI can affect the function of a number of remote organs. We review the short- and long-term clinical impact of AKI on other organ systems and potential mechanisms through which AKI may affect remote organ systems. Further elucidating the effects of AKI on remote organ function may lead to new therapeutic strategies to improve outcomes after AKI. PMID- 29798819 TI - Do patients benefit more from robot assisted approach than conventional laparoscopic distal pancreatectomy? A meta-analysis of perioperative and economic outcomes. AB - BACKGROUND/PURPOSE: Robotic approach has improved the ergonomics of conventional laparoscopic distal pancreatectomy (LDP), but whether patients benefit more from robot assisted distal pancreatectomy (RADP) is still controversial. This meta analysis aims to compare the perioperative and economic outcomes of RADP with LDP. METHODS: A systematic review of the literature was carried out on PubMed, EMBASE, and the Cochrane Library between January 1990 and March 2017. All eligible studies comparing RADP versus LDP were included. Perioperative and economic outcomes constituted the end points. RESULTS: 13 English studies with 1396 patients were included. Regarding to intraoperative outcomes, RADP was associated with a significant decrease in conversion rate (OR = 0.52; 95%CI: 0.34, 0.78; P = 0.002). Although the spleen-preserving rates were comparable between RADP and LDP, a significant higher splenic vessels conservation rate was observed in the RADP group (OR = 4.71; 95%CI: 1.77, 12.56; P = 0.002). No statistically significant differences were found at operation time, estimated blood loss and blood transfusion rate. Concerning postoperative outcomes, pooled data indicated the overall morbidity, pancreatic fistula and the length of hospital stay did not differ significantly between the RADP and LDP groups. And concerning pathological outcomes, positive margin rate and the number of lymph nodules harvested were comparable between the two groups. The operative cost of RADP was almost double that of LDP (WMD = 2350.2 US dollars; 95%CI: 1165.62, 3534.78; P = 0.0001). CONCLUSION: RADP showed a slight technical advantage. But whether this benefit is worth twofold cost should be considered by patient's individuation. PMID- 29798820 TI - A haplotype of MAP2K5/SKOR1 was associated with essential tremor in Chinese population. PMID- 29798821 TI - Tuberculosis and Microscopic Polyangiitis. A Rare Combination. PMID- 29798822 TI - Mental health, preoperative disability, and postoperative outcomes in patients undergoing shoulder arthroplasty. AB - BACKGROUND: Mental health conditions are associated with poor outcomes in patients with chronic disease as well as various orthopedic conditions. The purpose of this study was to describe the relationship between mental health, preoperative disability, and postoperative outcomes in patients undergoing shoulder arthroplasty. METHODS: Data, including mental health diagnoses, were prospectively collected from patients undergoing total shoulder arthroplasty or reverse total shoulder arthroplasty from 2009 to 2015 at a single academic institution. Shoulder range of motion, visual analog scale, 12-Item Short Form Health Survey, and American Shoulder and Elbow Surgeons scores were collected preoperatively and at 1 and 2 years postoperatively. Data were analyzed using multivariate mixed-effect regression analysis. RESULTS: The study included 280 patients, 105 (37.5%) of whom had a mental health diagnosis of depression, anxiety, schizophrenia, or bipolar disorder. Both groups of patients had similar shoulder range of motion, pain, and function before shoulder arthroplasty. Hospital length of stay, discharge destination, and readmissions were similar for both groups. There were similar improvements in pain, function, and range of motion after shoulder arthroplasty in patients with and without diagnosed mental health conditions. CONCLUSIONS: Overall, the presence of a psychiatric diagnosis was not predictive of outcomes. Although psychiatric conditions are often considered surgical comorbidities, mental health diagnoses should not be a barrier to performing clinically indicated shoulder arthroplasty, because both groups of patients appear to benefit from pain relief and improved shoulder function. PMID- 29798824 TI - Predicting adverse events, length of stay, and discharge disposition following shoulder arthroplasty: a comparison of the Elixhauser Comorbidity Measure and Charlson Comorbidity Index. AB - BACKGROUND: Rising health care expenditures and the adoption of bundled-care initiatives require efficient resource allocation for shoulder arthroplasty. To determine a reliable and accessible metric for implementing perioperative care pathways, we compared the accuracy of the Elixhauser Comorbidity Measure (ECM) and Charlson Comorbidity Index (CCI) for predicting adverse events and postoperative discharge destination after shoulder arthroplasty. MATERIALS AND METHODS: The National Inpatient Sample was queried for patients who underwent total shoulder arthroplasty or reverse total shoulder arthroplasty between 2002 and 2014. Logistic regression models were constructed with basic demographic variables and either the ECM or the CCI to predict inpatient deaths, complications, extended length of stay, and discharge disposition. The predictive discrimination of each model was evaluated using the concordance statistic (C statistic). RESULTS: We identified a total of 90,491 patients. The model incorporating both basic demographic variables and the complete set of ECM comorbidity variables provided the best predictive model, with a C-statistic of 0.867 for death, 0.752 for extended length of stay, and 0.81 for nonroutine discharge. The model's discrimination for postoperative complications was good, with C-statistics ranging from 0.641 to 0.879. CONCLUSION: A predictive model using the ECM outperforms models using the CCI for anticipating resource utilization following shoulder arthroplasty. Our results may assist value-based reimbursement methods to promote quality of care and reduce health care expenditures. PMID- 29798823 TI - A randomized controlled trial of arthroscopic capsular release versus hydrodilatation in the treatment of primary frozen shoulder. AB - BACKGROUND: Arthroscopic capsular release (ACR) and hydrodilatation (HD) have been developed for the management of frozen shoulder refractory to conservative treatment. To date no randomized trial has directly compared the efficacy of both interventions. The aim of this trial was to determine whether the Oxford Shoulder Score (OSS) differs between patients with frozen shoulder randomized to treatment with ACR or HD. METHODS: Patients presenting with severe idiopathic frozen shoulder deemed suitable for surgical intervention by a consultant shoulder surgeon were randomized to ACR or HD. The primary outcome measure was OSS at 6 months, with secondary outcomes measures of the EuroQol-5D visual analog scale, external rotation, complications, and crossover rate also recorded. RESULTS: Between June 2013 and December 2016, 50 patients were randomized to HD or ACR. The average age of the HD and ACR cohorts was 55.2 and 52.6 years, respectively (P = .36). At 6 months after the intervention, 20 patients were available for follow-up in the HD cohort and 19 in the ACR cohort. Both groups demonstrated significant improvements in OSS from baseline, but the OSS was significantly higher in the ACR cohort than the HD cohort (43.8 vs. 38.5, P = .023). The OSS was noted to improve rapidly after the intervention, with 75% of improvement in OSS noted at 6 weeks after surgery in both groups. CONCLUSIONS: Patients randomized to ACR reported a significantly higher OSS at 6 months than those randomized to HD. Both groups, however, showed a significant improvement. PMID- 29798826 TI - Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity, CoMFA and CoMSIA studies. AB - A series of novel furo[2,3-b]pyridine-2-carboxamide 4a h/pyrido[3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a-p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with alpha-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff's bases 7a-h and pyrido [3',2':4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a-h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a-h, 5a-p, 7a-h and 8a-h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors. PMID- 29798825 TI - Development of autotaxin inhibitors: A series of zinc binding triazoles. AB - A series of inhibitors of Autotaxin (ATX) has been developed using the binding mode of known inhibitor, PF-8380, as a template. Replacement of the benzoxazolone with a triazole zinc-binding motif reduced crystallinity and improved solubility relative to PF-8380. Modification of the linker region removed hERG activity and led to compound 12 - a selective, high affinity, orally-bioavailable inhibitor of ATX. Compound 12 concentration-dependently inhibits autotaxin and formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic experiments. PMID- 29798827 TI - Isoxazole-tethered diarylheptanoid analogs: Discovery of a new drug-like PAR2 antagonist. AB - A new class of isoxazole-tethered diarylheptanoids having characteristic 1,3-syn diol and 1,3-anti-diol chemophoric moieties, e.g. 4a-d and 5a-c respectively, have been designed and synthesized starting from d-glucose following a stereo conserved general synthetic strategy. The isoxazole heterocycle was installed using our recently elaborated methodology deploying MagtrieveTM as a selective oxidizing agent. Two of these new analogs 4a and 5a exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin-I. In a HEK293 cell-based intracellular calcium [Ca2+]i release assay, 4a and 5a, when tested at 30 MUM, inhibited the trypsin agonist induced protease activated receptor-2 (PAR2) activity by 80% and 70% respectively. IC50 of 4a (SB70) has been determined as 6 MUM which is in the same range of current benchmarks for PAR2 antagonists. PMID- 29798828 TI - Attitudes towards motherhood of women with physical versus psychiatric disabilities. AB - BACKGROUND: Women with disabilities may face social negative attitudes with regard to their being mothers. In addition, attitudes toward different disabilities form a hierarchy, with more positive attitudes being displayed toward persons with physical disabilities than toward persons with psychiatric disabilities. OBJECTIVE: Current observational study examined whether the relationship between a woman's type of disability (psychiatric vs. physical) and the social attitude towards her would be moderated by her being presented as a mother. METHOD: University students (N = 100) filled out the Multidimensional Attitudes Scale Toward Persons With Disabilities and the Social Distance Scale, after reading one of six randomly assigned fictitious vignettes. The vignettes consisted of a woman with a physical disability/a woman with a psychiatric disability/a woman without a disability, who either was or was not a mother. RESULTS: Type of disability was found to have a main effect in some attitude domains, suggesting that attitudes toward women with physical disabilities were better than attitudes towards women with psychiatric disabilities. An interaction between type of disability and motherhood was found for the interpersonal distress subscale of the attitudes scale. It was found that when women had physical disabilities, there was no change in attitude towards them regardless of whether they were presented as mothers or not; However, when the target woman had a psychiatric disability, and she was presented as a mother, negative attitudes were generated towards her. CONCLUSIONS: The study demonstrates the existence of a hierarchy of stigmatization and the effect of being a mother on stigmatization. PMID- 29798829 TI - Disability, stress, and health disparities. PMID- 29798830 TI - Neuromyelitis optica in Sub-Saharan Africa: the first case report from Togo. AB - Neuromyelitis optica (NMO) appears to affect blacks disproportionately in mixed populations. We report the first case of documented NMO in Togo (West Africa). A 26-year-old Togolese woman was admitted for progressive tetraplegia, acute urine retention, and dyspnea. Magnetic resonance imaging of the cervical spinal cord demonstrated an extensive longitudinal lesion, and an ophthalmologic examination found bilateral optic neuritis. Antibody testing for AQP4-IgG was positive. The patient died of severe respiratory distress despite high doses of intravenous corticosteroids. Epidemiological data about NMO in sub-Saharan Africa would improve our understanding of the role of genetic and environmental risk factors in this disease. PMID- 29798831 TI - A Web-Based Transdiagnostic Intervention for Affective and Mood Disorders: Randomized Controlled Trial. AB - BACKGROUND: Research increasingly supports a transdiagnostic conceptualization of emotional disorders (ie applying the same underlying treatment principles across mental disorders, without tailoring the protocol to specific diagnoses), and many international researchers are currently investigating this issue. OBJECTIVE: The aim of this study was to evaluate the efficacy and acceptability of a Web-based transdiagnostic program using a sample of Romanian adults diagnosed with anxiety and/or depression. METHODS: Volunteer participants registered for the study and completed a series of online self-report measures. Participants who fulfilled basic inclusion criteria on these measures were contacted for a telephone diagnostic interview using the Structural Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders (SCID-I). Enrolled participants were randomized to either the active treatment group (N=69) or the wait-list control group (N=36) using a 2:1 ratio. The transdiagnostic treatment was based on the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP; Barlow et al, 2011) that addresses common underlying mechanisms of anxiety and depression. Participants randomized to the active treatment condition received 10 weeks of Web-based treatment based on the UP. Throughout treatment, graduate students in clinical psychology provided guidance that consisted of asynchronous written communication on a secure Web platform. After the intervention, participants in both study conditions were invited to complete a set of self-report measures and a postintervention SCID-I interview conducted by a different team of graduate students blinded to participants' group and diagnostic status. Six months later, participants in the active treatment group were invited to complete an online follow-up assessment. RESULTS: During the intervention, active treatment participants completed on average 19 homework assignments (SD 12.10), and we collected data from 79.0% (83/105) at postintervention and 51% (35/69) at follow-up for self-report measures. Postintervention SCID-I interviews were collected from 77.1% (81/105) participants. Relative to the wait-list control group, the transdiagnostic intervention yielded overall medium to large effect sizes for the primary outcome measures (within-group Hedges g=0.52-1.34 and between-group g=0.39-0.86), and also for anxiety sensitivity (g=0.80), symptom interference (g=0.48), and quality of life (g=0.38). Significant within-groups effects only were reported for the active treatment group on Panic Disorder Severity Scale-Self Report (PDSS-SR, g=0.58-0.65) and Yale-Brown Obsessive Compulsive Scale (Y-BOCS, g=0.52-0.58). CONCLUSIONS: Insignificant between-group differences for the Y-BOCS and PDSS-SR could be explained by the small number of participants with the associated primary diagnostic (eg, only 3 participants with obsessive compulsive disorder) by the choice of outcome measure (PDSS-SR was not rated among the evidence-based measures) and by the fact that these disorders may be more difficult to treat. However, the overall results suggest that the transdiagnostic intervention tested in this study represents an effective treatment option that may prove easier to disseminate through the use of Web-based delivery systems. TRIAL REGISTRATION: ClinicalTrials.gov CT02739607; https://clinicaltrials.gov/ct2/show/study/NCT02739607 (Archived by WebCite at http://www.webcitation.org/6yY1VeYIZ). PMID- 29798832 TI - TEAMS (Tele-Exercise and Multiple Sclerosis), a Tailored Telerehabilitation mHealth App: Participant-Centered Development and Usability Study. AB - BACKGROUND: People with multiple sclerosis face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation, and travel distance. Generic mobile health exercise apps often fall short of what people with multiple sclerosis need to become physically active (ie, exercise content that has been adapted to accommodate a wide range of functional limitations). OBJECTIVE: This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with multiple sclerosis in a large randomized controlled trial to engage in home-based telerehabilitation. METHODS: Twenty-one participants with disabilities (10 people with multiple sclerosis) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design approach, the development process included 2 stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through 2 usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated using a mixed-methods approach. RESULTS: During testing of the app's effectiveness, the second usability test resulted in an average of 1 problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to app usefulness and satisfaction, namely: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the randomized controlled trial. CONCLUSIONS: A multi-level user-centered development process resulted in the development of an inclusive exercise program for people with multiple sclerosis operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (ie, people with varying levels of multiple sclerosis). PMID- 29798834 TI - Important considerations for interpreting biochemical tests in children. PMID- 29798833 TI - Exploring the Waveform Characteristics of Tidal Breathing Carbon Dioxide, Measured Using the N-Tidal C Device in Different Breathing Conditions (The General Breathing Record Study): Protocol for an Observational, Longitudinal Study. AB - BACKGROUND: In an increasingly comorbid population, there are significant challenges to diagnosing the cause of breathlessness, and once diagnosed, considerable difficulty in detecting deterioration early enough to provide effective intervention. The burden of the breathless patient on the health care economy is substantial, with asthma, chronic heart failure, and pneumonia affecting over 6 million people in the United Kingdom alone. Furthermore, these patients often have more than one contributory factor to their breathlessness symptoms, with conditions such as dysfunctional breathing pattern disorders-an under-recognized component. Current methods of diagnosing and monitoring breathless conditions can be extensive and difficult to perform. As a consequence, home monitoring is poorly complied with. In contrast, capnography (the measurement of tidal breath carbon dioxide) is performed during normal breathing. There is a need for a simple, easy-to-use, personal device that can aid in the diagnosis and monitoring of respiratory and cardiac causes of breathlessness. OBJECTIVE: The aim of this study was to explore the use of a new, handheld capnometer (called the N-Tidal C) in different conditions that cause breathlessness. We will study whether the tidal breath carbon dioxide (TBCO2) waveform, as measured by the N-Tidal C, has different characteristics in a range of respiratory and cardiac conditions. METHODS: We will perform a longitudinal, observational study of the TBCO2 waveform (capnogram) as measured by the N-Tidal C capnometer. Participants with a confirmed diagnosis of asthma, breathing pattern disorders, chronic heart failure, motor neurone disease, pneumonia, as well as volunteers with no history of lung disease will be asked to provide twice daily, 75-second TBCO2 collection via the N-Tidal C device for 6 months duration. The collated capnograms will be correlated with the underlying diagnosis and disease state (stable or exacerbation) to determine if there are different TBCO2 characteristics that can distinguish different respiratory and cardiac causes of breathlessness. RESULTS: This study's recruitment is ongoing. It is anticipated that the results will be available in late 2018. CONCLUSIONS: The General Breathing Record Study will provide an evaluation of the use of capnography as a diagnostic and home-monitoring tool for various diseases. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9767. PMID- 29798835 TI - Antiplatelet Therapy, Cerebral Microbleeds, and Intracerebral Hemorrhage: A Meta Analysis. AB - BACKGROUND AND PURPOSE: Antiplatelet therapy is associated with the presence of cerebral microbleeds (CMBs) with limited studies. We further investigate the topic focusing on different effects of antiplatelet therapy on strict lobar and deep/infratentorial MBs. METHODS: We searched PubMed and EMBASE from January 1, 1997 to December 1, 2017, for relevant studies, calculated the pooled odds ratios (OR) for CMB incidence and distribution (strictly lobar, deep/infratentorial) in antiplatelet users versus nonantiplatelet users and calculated the OR for the incidence of intracerebral hemorrhage in antiplatelet users with CMBs versus those without. RESULTS: We included 20 988 participants from 37 studies. CMBs were more frequent in antiplatelet users than those in nonantiplatelet users (pooled OR, 1.21; 95% confidence interval, 1.07-1.36; P=0.002). There was a significant association of antiplatelet therapy with strictly lobar MBs (OR, 1.45; 95% confidence interval, 1.15-1.84; P=0.002) rather than deep/infratentorial MBs (OR, 1.37; 95% confidence interval, 0.98-1.90; P=0.062). Intracerebral hemorrhage incidence was higher in participants with CMBs than those without CMBs (OR, 3.40; 95% confidence interval, 2.00-5.78; P=0.000) in antiplatelet users. CONCLUSIONS: Antiplatelet drug use was associated with increased risk of strictly lobar MBs and increased the intracerebral hemorrhage incidence in participants with CMBs. PMID- 29798836 TI - Seven days in medicine: 16-22 May 2018. PMID- 29798837 TI - Nerve ablation reduced blood pressure in two thirds of patients, trial finds. PMID- 29798839 TI - A simple technique to construct tissue macroarrays. AB - AIMS: In the diagnostic or research field, there is a need that the histopathological evaluation provides as much information as possible, with the shortest time and lowest cost. The development of the tissue microarray (TMA) technology has significantly facilitated and accelerated studies with tissue analyses using in situ technologies. Nevertheless, one of the most recognised limitations of TMA is that the small cores used to construct a TMA may not accurately represent characteristics of the whole tissue specimen. The aim is to present the technical aspects of a simple system to construct tissue macroarrays (TMaAs), its advantages and limitations, and some results of its use in for research purposes. METHODS: The study presents three possibilities of preparing the specimens with up to 6 mm diameter to be included into the TMaA paraffin block using our method. RESULTS: With this technique, it was possible to obtain glass slides with multiple whole fragments, which were used in five different studies. CONCLUSIONS: We presented a method for construction of multi-TMaA paraffin blocks, which is very simple for optimising laboratory techniques requiring paraffin-embedded tissue sections and can be easily implemented in any institution with a histology laboratory. PMID- 29798840 TI - Importance of pharmacology to avoid complications with endoscopic sedation. PMID- 29798838 TI - Idylla assay and next generation sequencing: an integrated EGFR mutational testing algorithm. AB - AIMS: Any reference laboratory testing non-small cell lung cancer samples for predictive biomarkers needs to develop and validate a wide range of different molecular techniques, each with a specific time requirement and application. Updated international guidelines suggest that next generation sequencing (NGS) to be the initial procedure. However, in a non-negligible subset of cases, library generation may fail or amplicon coverage may be insufficient. In these NGS 'invalid' cases, the Idylla system may represent a viable option for rapid epidermal growth factor receptor (EGFR) genotyping. METHODS: This retrospective study included 68 archival DNA samples previously processed by Ion Torrent NGS assay. Out of these, 43 cases, including 24 EGFR mutant samples, had a valid NGS result, whereas 25/68 (37%) were invalid. All samples were retested by directly pipetting the DNA inside the EGFR Idylla assay cartridge. RESULTS: In all 43 cases with a valid NGS result, Idylla confirmed the EGFR mutational status. In particular, 24/24 (100%) of EGFR mutant samples as detected by NGS were confirmed by Idylla. Moreover, a large portion of cases (20/25; 80%) whose assessment by NGS was invalid were adequately processed by Idylla. Noteworthy, in 4/25 (16%) of cases, Idylla detected actionable EGFR mutations. CONCLUSIONS: Idylla assay could be very useful to quickly process cases for which NGS does not allow genotyping. PMID- 29798841 TI - Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice. AB - OBJECTIVE: Nardilysin (NRDC), a zinc peptidase, exhibits multiple localisation dependent functions including as an enhancer of ectodomain shedding in the extracellular space and a transcriptional coregulator in the nucleus. In this study, we investigated its functional role in exocrine pancreatic development, homeostasis and the formation of pancreatic ductal adenocarcinoma (PDA). DESIGN: We analysed Ptf1a-Cre; Nrdcflox/flox mice to investigate the impact of Nrdc deletion. Pancreatic acinar cells were isolated from Nrdcflox/flox mice and infected with adenovirus expressing Cre recombinase to examine the impact of Nrdc inactivation. Global gene expression in Nrdc-cKO pancreas was analysed compared with wild-type pancreas by microarray analysis. We also analysed Ptf1a-Cre; KrasG12D; Nrdcflox/flox mice to investigate the impact of Nrdc deletion in the context of oncogenic Kras. A total of 51 human samples of pancreatic intraepithelial lesions (PanIN) and PDA were examined by immunohistochemistry for NRDC. RESULTS: We found that pancreatic deletion of Nrdc leads to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, increased apoptosis and atrophic pancreas in mice. Acinar-to-ductal conversion was observed mainly through a non-cell autonomous mechanism, and the expression of several chemokines was significantly increased in Nrdc-null pancreatic acinar cells. Furthermore, pancreatic deletion of Nrdc dramatically accelerated KrasG12D driven PanIN and subsequent PDA formation in mice. These data demonstrate a previously unappreciated anti-inflammatory and tumour suppressive functions of Nrdc in the pancreas in mice. Finally, absence of NRDC expression was observed in a subset of human PanIN and PDA. CONCLUSION: Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. PMID- 29798842 TI - Effect of embryo transfer technique on the likelihood of pregnancy in the mare: a comparison of conventional and Wilsher's forceps-assisted transfer. AB - The aim of this study was to compare the success of embryo transfer (ET) performed by veterinarians with different degrees of experience using one of two ET techniques. Over three years, 179 embryos were transferred by three operators with moderate to high experience using a 'conventional' manual technique, and 170 embryos were transferred by four operators with little or no previous ET experience using a 'Wilsher' technique (Polansky speculum and Wilsher's cervical forceps). The pregnancy status of recipient mares at the first pregnancy diagnosis and the embryo loss by the last examination were compared between groups and within group among operators. More recipients became pregnant (P<0.005) following ET with the Wilsher technique (157/170; 92.3 per cent) than with the conventional technique (127/179; 70.9 per cent), while the incidence of pregnancy loss did not differ between the groups (9.1 v 7.9 per cent, respectively). For the conventional technique, there was a significant operator effect (P<0.01) on the percentage of pregnant recipients at the first examination (50.9-79.7 per cent); no operator effect was apparent for the Wilsher technique (90.9-93.4 per cent). In conclusion, the Wilsher technique yielded high pregnancy rates (>90 per cent). PMID- 29798843 TI - A novel de novo CDH1 germline variant aids in the classification of carboxy terminal E-cadherin alterations predicted to escape nonsense-mediated mRNA decay. AB - Most truncating cadherin 1 (CDH1) pathogenic alterations confer an elevated lifetime risk of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). However, transcripts containing carboxy-terminal premature stop codons have been demonstrated to escape the nonsense-mediated mRNA decay pathway, and gastric and breast cancer risks associated with these truncations should be carefully evaluated. A female patient underwent multigene panel testing because of a personal history of invasive LBC diagnosed at age 54, which identified the germline CDH1 nonsense alteration, c.2506G>T (p.Glu836*), in the last exon of the gene. Subsequent parental testing for the alteration was negative and additional short tandem repeat analysis confirmed the familial relationships and the de novo occurrence in the proband. Based on the de novo occurrence, clinical history, and rarity in general population databases, this alteration was classified as a likely pathogenic variant. This is the most carboxy-terminal pathogenic alteration reported to date. Additionally, this alteration contributed to the classification of six other upstream CDH1 carboxy-terminal truncating variants as pathogenic or likely pathogenic. Identifying the most distal pathogenic alteration provides evidence to classify other carboxy-terminal truncating variants as either pathogenic or benign, a fundamental step to offering presymptomatic screening and prophylactic procedures to the appropriate patients. PMID- 29798844 TI - In vivo aerobic metabolism of the rainbow trout gut and the effects of an acute temperature increase and stress event. AB - The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10 degrees C, gut oxygen uptake rate was 4.3+/-0.5 ml O2 h-1 kg-1 (~11% of whole-animal oxygen uptake). Following acute warming to 15 degrees C, gut blood flow increased ~3.4-fold and gut oxygen uptake rate increased ~3.7-fold (16.0+/ 3.3 ml O2 h-1 kg-1), now representing ~25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15 degrees C, gut oxygen uptake remained unchanged as a result of a ~2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation. PMID- 29798845 TI - Can honey bees discriminate between floral-fragrance isomers? AB - Many flowering plants present variable complex fragrances, which usually include different isomers of the same molecule. As fragrance is an essential cue for flower recognition by pollinators, we ask whether honey bees discriminate between floral-fragrance isomers in an appetitive context. We used the olfactory conditioning of the proboscis extension response, which allows training a restrained bee to an odor paired with sucrose solution. Bees were trained under an absolute (a single odorant rewarded) or a differential conditioning regime (a rewarded versus a non-rewarded odorant) using four different pairs of isomers. One hour after training, discrimination and generalization between pairs of isomers were tested. Bees trained under absolute conditioning exhibited high generalization between isomers and discriminated only one out of four isomer pairs; after differential conditioning, they learned to differentiate between two out of four pairs of isomers but in all cases generalization responses to the non rewarding isomer remained high. Adding an aversive taste to the non-rewarded isomer facilitated discrimination of isomers that otherwise seemed non discriminable but generalization remained high. Although honey bees discriminated isomers under certain conditions, they achieved the task with difficulty and tended to generalize between them, thus showing that these molecules were perceptually similar to them. We conclude that the presence of isomers within floral fragrances might not necessarily contribute to a dramatic extent to floral odor diversity. PMID- 29798846 TI - Contribution of a natural polymorphism in protein kinase G modulates electroconvulsive seizure recovery in Drosophila melanogaster. AB - Drosophila melanogaster is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval D. melanogaster with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG). PKG, encoded by foraging, has two natural allelic variants and has previously been implicated in several important physiological characteristics including: foraging patterns, learning and memory, and environmental stress tolerance. The well established NO/cGMP/PKG signaling pathway found in the fly, which potentially targets downstream K+ channel(s), ultimately impacts membrane excitability, leading to our hypothesis: altering PKG enzymatic activity modulates time to recovery from an electroconvulsive seizure. Our results show that by both genetically and pharmacologically increasing PKG enzymatic activity, we can decrease the locomotor recovery time from an electroconvulsive seizure in larval D. melanogaster. PMID- 29798847 TI - Rapid depth perception in hunting archerfish. I. The predictive C-starts use an independent estimate of target height. AB - Archerfish dislodge aerial prey with water jets and use their predictive C-starts to secure it. Their C-starts turn the fish to the later point of impact and set the speed so that the fish arrive just in time. The starts are adjusted on the basis of information on speed, direction, timing and horizontal start position of prey movement - sampled during less than 100 ms after prey starts falling. Presently, it is unclear whether one essential parameter, the initial height of prey, can also be determined during this brief sampling time. Shooters and probably also observing bystanders already know target height - used to hit and to shape their jets - and would simply have to feed this information into their C start circuitry. We challenged archerfish by launching initially invisible prey objects either from the expected height level, at which the fish were looking and at which they fired shots, or from more lateral positions and a lower or higher initial height. The arrangement was designed so that an analysis of the direction and the linear speed chosen by the starting fish could determine whether the C start information is based on the expected height or on the actual height, which can be detected only after hidden prey has begun falling. Our findings demonstrate that the fish quickly estimate initial height during the initial falling phase of prey and do not simply use the expected height level to which they were cued. PMID- 29798848 TI - Rapid depth perception in hunting archerfish. II. An analysis of potential cues. AB - Based on the initial movement of falling prey, hunting archerfish select a C start that turns them right to where their prey is going to land and lends the speed to arrive simultaneously with prey. Our companion study suggested that the information sampled in less than 100 ms also includes the initial height of falling prey. Here, we examine which cues the fish might be using to gauge height so quickly. First, we show that binocular cues are not required: C-starts that either could or could not have used binocular information were equally fast and precise. Next, we explored whether the fish were using simplifying assumptions about the absolute size of their prey or its distance from a structured background. However, experiments with unexpected changes from the standard conditions failed to cause any errors. We then tested the hypothesis that the fish might infer depth from accommodation or from cues related to blurring in the image of their falling prey. However, the fish also determined the height of 'fake flies' correctly, even though their image could never be focused and their combined size and degree of blurring should have misled the fish. Our findings are not compatible with the view that archerfish use a flexible combination of cues. They also do not support the view that height is gauged relative to structures in the vicinity of starting prey. We suggest that these fish use an elaborate analysis of looming to rapidly gauge initial height. PMID- 29798849 TI - Biomechanical factors influencing successful self-righting in the pleurodire turtle Emydura subglobosa. AB - Self-righting performance is a key ability for most terrestrial animals, and has been used as a metric of fitness, exhaustion and thermal limits in a variety of taxa. However, there is little understanding of the underlying mechanisms that drive variation in self-righting performance. To evaluate the mechanical factors that contribute to success versus failure when animals attempt to self-right, we compared force production and kinematic behavior in the rigid-bodied, pleurodire turtle Emydura subglobosa between successful and unsuccessful self-righting efforts. We found that the moment exerted during efforts to roll the body and the velocity of that roll are the primary drivers behind self-righting success. Specifically, turtles that self-righted successfully produced both larger moments and faster rolls than turtles that failed. In contrast, the angle at which the head was directed to lever the body and the extent of yaw that was incorporated in addition to roll had little impact on the likelihood of success. These results show that specific performance metrics can predict the ability of animals to self right, providing a framework for biomimetic applications as well as future comparisons to test for differences in self-righting performance across animals from different environments, sexes, populations and species. PMID- 29798850 TI - Examination of needle surface corrosion in electroacupuncture. AB - BACKGROUND: Electroacupuncture (EA) is a modern form of acupuncture therapy where stainless steel acupuncture needles are used as percutaneous electrodes to apply electrical stimulation. The concern about electrolytic corrosion of needles during EA has not been conclusively addressed. AIM: To examine whether corrosion of stainless steel acupuncture needles occurs after EA to establish the safety profile of this therapy. METHODS: The study comprised four EA sessions on healthy participants mimicking a common clinical practice, with needle surface examinations conducted immediately after each session. Used acupuncture needles that did not undergo electrical stimulation and unused needles taken from the original package were also examined as control comparisons. Two commonly used types of single-use, silicone-coated, stainless steel needles were selected for the experiment. The ES-160 digital acupunctoscope (a charge-balanced electric stimulator) was used to deliver electrical stimulation, and an oscilloscope was used to record the waveforms and electric currents. All needles were sterilised before examination by a scanning electron microscope (SEM), where images of needle tips and shafts were taken for further analysis. RESULTS AND CONCLUSIONS: 32 needles were examined under the SEM. As the main findings, the SEM images showed the surface finish, burr attachments and surface characteristics of needle samples. No evidence of electrolytic corrosion was detected on any needle that underwent electrical stimulation for 30 min delivered by a charge-balanced acupunctoscope in healthy participants. The choice of a charge-balanced acupunctoscope is recommended to avoid any potential corrosion of needles in EA clinical practice. PMID- 29798852 TI - Comment on "Plant diversity increases with the strength of negative density dependence at the global scale". AB - LaManna et al (Reports, 30 June 2017, p. 1389) claim that subadult trees are proportionally less common at high conspecific adult density (CNDD) and that this effect increases toward the tropics and for rare species. We show that the CNDD abundance correlation may have arisen from a methodological artifact and that a range of processes can explain the reported latitudinal pattern. PMID- 29798851 TI - Evaluating recovery potential of the northern white rhinoceros from cryopreserved somatic cells. AB - The critically endangered northern white rhinoceros is believed to be extinct in the wild, with the recent death of the last male leaving only two remaining individuals in captivity. Its extinction would appear inevitable, but the development of advanced cell and reproductive technologies such as cloning by nuclear transfer and the artificial production of gametes via stem cells differentiation offer a second chance for its survival. In this work, we analyzed genome-wide levels of genetic diversity, inbreeding, population history, and demography of the white rhinoceros sequenced from cryopreserved somatic cells, with the goal of informing how genetically valuable individuals could be used in future efforts toward the genetic rescue of the northern white rhinoceros. We present the first sequenced genomes of the northern white rhinoceros, which show relatively high levels of heterozygosity and an average genetic divergence of 0.1% compared with the southern subspecies. The two white rhinoceros subspecies appear to be closely related, with low genetic admixture and a divergent time <80,000 yr ago. Inbreeding, as measured by runs of homozygosity, appears slightly higher in the southern than the northern white rhinoceros. This work demonstrates the value of the northern white rhinoceros cryopreserved genetic material as a potential gene pool for saving this subspecies from extinction. PMID- 29798854 TI - Comment on "Plant diversity increases with the strength of negative density dependence at the global scale". AB - LaManna et al (Reports, 30 June 2017, p. 1389) found higher conspecific negative density dependence in tree communities at lower latitudes, yielding a possible mechanistic explanation for the latitudinal diversity gradient. We show that their results are artifacts of a selective data transformation and a forced zero intercept in their fitted model. A corrected analysis shows no latitudinal trend. PMID- 29798853 TI - Response to Comment on "Plant diversity increases with the strength of negative density dependence at the global scale". AB - Hulsmann and Hartig suggest that ecological mechanisms other than specialized natural enemies or intraspecific competition contribute to our estimates of conspecific negative density dependence (CNDD). To address their concern, we show that our results are not the result of a methodological artifact and present a null-model analysis that demonstrates that our original findings-(i) stronger CNDD at tropical relative to temperate latitudes and (ii) a latitudinal shift in the relationship between CNDD and species abundance-persist even after controlling for other processes that might influence spatial relationships between adults and recruits. PMID- 29798859 TI - News at a glance. PMID- 29798855 TI - Response to Comment on "Plant diversity increases with the strength of negative density dependence at the global scale". AB - Chisholm and Fung claim that our method of estimating conspecific negative density dependence (CNDD) in recruitment is systematically biased, and present an alternative method that shows no latitudinal pattern in CNDD. We demonstrate that their approach produces strongly biased estimates of CNDD, explaining why they do not detect a latitudinal pattern. We also address their methodological concerns using an alternative distance-weighted approach, which supports our original findings of a latitudinal gradient in CNDD and a latitudinal shift in the relationship between CNDD and species abundance. PMID- 29798858 TI - Canada's call. PMID- 29798860 TI - Rival giant telescopes join to seek U.S. funding. PMID- 29798861 TI - China's ambitious brain science project inches forward. PMID- 29798856 TI - Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. AB - Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-gamma production upon antigen stimulation. In vivo functional studies showed that NKT cells mediated liver-selective tumor inhibition. NKT cell accumulation was regulated by CXCL16 expression of liver sinusoidal endothelial cells, which was controlled by gut microbiome-mediated primary-to-secondary bile acid conversion. Our study suggests a link between gut bacteria-controlled bile acid metabolism and liver antitumor immunosurveillance. PMID- 29798862 TI - German law allows use of DNA to predict suspects' looks. PMID- 29798857 TI - Beyond fossil fuel-driven nitrogen transformations. AB - Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle. These approaches, as well as the challenges involved, are discussed in this Review. PMID- 29798863 TI - B612 plans asteroid hunt with fleet of small satellites. PMID- 29798864 TI - A call to arms against the other retrovirus. PMID- 29798865 TI - Basic instincts. PMID- 29798866 TI - The war on gluten. PMID- 29798867 TI - Following the leader, for better or worse. PMID- 29798868 TI - Enhancing energy transport in conjugated polymers. PMID- 29798869 TI - Cold chemistry with two atoms. PMID- 29798870 TI - Illuminating dark depths. PMID- 29798871 TI - Cancer immunity thwarted by the microbiome. PMID- 29798872 TI - The RNA face of phase separation. PMID- 29798873 TI - Disparities in science literacy. PMID- 29798875 TI - NextGen VOICES: Submit Now: Broad interests: Benefits for science. PMID- 29798876 TI - The road to wild yak protection in China. PMID- 29798874 TI - Brazil's government attacks biodiversity. PMID- 29798877 TI - Trout in hot water: A call for global action. PMID- 29798878 TI - A 550,000-year record of East Asian monsoon rainfall from 10Be in loess. AB - Cosmogenic 10Be flux from the atmosphere is a proxy for rainfall. Using this proxy, we derived a 550,000-year-long record of East Asian summer monsoon (EASM) rainfall from Chinese loess. This record is forced at orbital precession frequencies, with higher rainfall observed during Northern Hemisphere summer insolation maxima, although this response is damped during cold interstadials. The 10Be monsoon rainfall proxy is also highly correlated with global ice-volume variations, which differs from Chinese cave delta18O, which is only weakly correlated. We argue that both EASM intensity and Chinese cave delta18O are not governed by high-northern-latitude insolation, as suggested by others, but rather by low-latitude interhemispheric insolation gradients, which may also strongly influence global ice volume via monsoon dynamics. PMID- 29798879 TI - Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction. AB - Identifying catalyst activation modes that exploit one-electron chemistry and overcome associated deactivation pathways will be transformative for developing first-row transition metal catalysts with performance equal or, ideally, superior to precious metals. Here we describe a zinc-activation method compatible with high-throughput reaction discovery that identified scores of cobalt-phosphine combinations for the asymmetric hydrogenation of functionalized alkenes. An optimized catalyst prepared from (R,R)-Ph-BPE {Ph-BPE, 1,2-bis[(2R,5R)-2,5 diphenylphospholano]ethane} and cobalt chloride [CoCl2.6H2O] exhibited high activity and enantioselectivity in protic media and enabled the asymmetric synthesis of the epilepsy medication levetiracetam at 200-gram scale with 0.08 mole % catalyst loading. Stoichiometric studies established that the cobalt (II) catalyst precursor (R,R)-Ph-BPECoCl2 underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine. PMID- 29798880 TI - Imaging of pure spin-valley diffusion current in WS2-WSe2 heterostructures. AB - Transition metal dichalcogenide (TMDC) materials are promising for spintronic and valleytronic applications because valley-polarized excitations can be generated and manipulated with circularly polarized photons and the valley and spin degrees of freedom are locked by strong spin-orbital interactions. In this study we demonstrate efficient generation of a pure and locked spin-valley diffusion current in tungsten disulfide (WS2)-tungsten diselenide (WSe2) heterostructures without any driving electric field. We imaged the propagation of valley current in real time and space by pump-probe spectroscopy. The valley current in the heterostructures can live for more than 20 microseconds and propagate over 20 micrometers; both the lifetime and the diffusion length can be controlled through electrostatic gating. The high-efficiency and electric-field-free generation of a locked spin-valley current in TMDC heterostructures holds promise for applications in spin and valley devices. PMID- 29798881 TI - Long-range exciton transport in conjugated polymer nanofibers prepared by seeded growth. AB - Easily processed materials with the ability to transport excitons over length scales of more than 100 nanometers are highly desirable for a range of light harvesting and optoelectronic devices. We describe the preparation of organic semiconducting nanofibers comprising a crystalline poly(di-n-hexylfluorene) core and a solvated, segmented corona consisting of polyethylene glycol in the center and polythiophene at the ends. These nanofibers exhibit exciton transfer from the core to the lower-energy polythiophene coronas in the end blocks, which occurs in the direction of the interchain pi-pi stacking with very long diffusion lengths (>200 nanometers) and a large diffusion coefficient (0.5 square centimeters per second). This is made possible by the uniform exciton energetic landscape created by the well-ordered, crystalline nanofiber core. PMID- 29798882 TI - High parasite diversity accelerates host adaptation and diversification. AB - Host-parasite species pairs are known to coevolve, but how multiple parasites coevolve with their host is unclear. By using experimental coevolution of a host bacterium and its viral parasites, we revealed that diverse parasite communities accelerated host evolution and altered coevolutionary dynamics to enhance host resistance and decrease parasite infectivity. Increases in parasite diversity drove shifts in the mode of selection from fluctuating (Red Queen) dynamics to predominately directional (arms race) dynamics. Arms race dynamics were characterized by selective sweeps of generalist resistance mutations in the genes for the host bacterium's cell surface lipopolysaccharide (a bacteriophage receptor), which caused faster molecular evolution within host populations and greater genetic divergence among populations. These results indicate that exposure to multiple parasites influences the rate and type of host-parasite coevolution. PMID- 29798883 TI - From local collective behavior to global migratory patterns in white storks. AB - Soaring migrant birds exploit columns of rising air (thermals) to cover large distances with minimal energy. Using social information while locating thermals may benefit such birds, but examining collective movements in wild migrants has been a major challenge for researchers. We investigated the group movements of a flock of 27 naturally migrating juvenile white storks by using high-resolution GPS and accelerometers. Analyzing individual and group movements on multiple scales revealed that a small number of leaders navigated to and explored thermals, whereas followers benefited from their movements. Despite this benefit, followers often left thermals earlier and at lower height, and consequently they had to flap considerably more. Followers also migrated less far annually than did leaders. We provide insights into the interactions between freely flying social migrants and the costs and benefits of collective movement in natural populations. PMID- 29798885 TI - What I learned from teaching. PMID- 29798886 TI - Race in America: What Does It Mean for Diabetes and CKD? PMID- 29798887 TI - Intensive Blood Pressure Targets and Kidney Disease. PMID- 29798884 TI - An ingestible bacterial-electronic system to monitor gastrointestinal health. AB - Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease. PMID- 29798888 TI - Target Blood Pressure for Cardiovascular Disease Prevention in Patients with CKD. PMID- 29798889 TI - Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes. AB - BACKGROUND AND OBJECTIVES: Type 2 diabetes and associated CKD disproportionately affect blacks. It is uncertain if racial disparities in type 2 diabetes associated CKD are driven by biologic factors that influence propensity to CKD or by differences in type 2 diabetes care. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a post hoc analysis of 1937 black and 6372 white participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to examine associations of black race with change in eGFR and risks of developing microalbuminuria, macroalbuminuria, incident CKD (eGFR<60 ml/min per 1.73m2, >=25% decrease from baseline eGFR, and eGFR slope <-1.6 ml/min per 1.73 m2 per year), and kidney failure or serum creatinine >3.3 mg/dl. RESULTS: During a median follow-up that ranged between 4.4 and 4.7 years, 278 black participants (58 per 1000 person-years) and 981 white participants (55 per 1000 person-years) developed microalbuminuria, 122 black participants (16 per 1000 person-years) and 374 white participants (14 per 1000 person-years) developed macroalbuminuria, 111 black participants (21 per 1000 person-years) and 499 white participants (28 per 1000 person-years) developed incident CKD, and 59 black participants (seven per 1000 person-years) and 178 white participants (six per 1000 person-years) developed kidney failure or serum creatinine >3.3 mg/dl. Compared with white participants, black participants had lower risks of incident CKD (hazard ratio, 0.73; 95% confidence intervals, 0.57 to 0.92). There were no significant differences by race in eGFR decline or in risks of microalbuminuria, macroalbuminuria, and kidney failure or of serum creatinine >3.3 mg/dl. CONCLUSIONS: Black participants enrolled in a randomized controlled trial had lower rates of incident CKD compared with white participants. Rates of eGFR decline, microalbuminuria, macroalbuminuria, and kidney failure did not vary by race. PMID- 29798893 TI - Meet the First Authors. PMID- 29798892 TI - Neural Dynamics of Variable Grasp-Movement Preparation in the Macaque Frontoparietal Network. AB - Our voluntary grasping actions lie on a continuum between immediate action and waiting for the right moment, depending on the context. Therefore, studying grasping requires an investigation into how preparation time affects this process. Two macaque monkeys (Macaca mulatta; one male, one female) performed a grasping task with a short instruction followed by an immediate or delayed go cue (0-1300 ms) while we recorded in parallel from neurons in the grasp preparation relevant area F5 that is part of the ventral premotor cortex, and the anterior intraparietal area (AIP). Initial population dynamics followed a fixed trajectory in the neural state space unique to each grip type, reflecting unavoidable movement selection, then diverged depending on the delay, reaching unique states not achieved for immediately cued movements. Population activity in the AIP was less dynamic, whereas F5 activity continued to evolve throughout the delay. Interestingly, neuronal populations from both areas allowed for a readout tracking subjective anticipation of the go cue that predicted single-trial reaction time. However, the prediction of reaction time was better from F5 activity. Intriguingly, activity during movement initiation clustered into two trajectory groups, corresponding to movements that were either "as fast as possible" or withheld movements, demonstrating a widespread state shift in the frontoparietal grasping network when movements must be withheld. Our results reveal how dissociation between immediate and delay-specific preparatory activity, as well as differentiation between cortical areas, is possible through population-level analysis.SIGNIFICANCE STATEMENT Sometimes when we move, we consciously plan our movements. At other times, we move instantly, seemingly with no planning at all. Yet, it's unclear how preparation for movements along this spectrum of planned and seemingly unplanned movement differs in the brain. Two macaque monkeys made reach-to-grasp movements after varying amounts of preparation time while we recorded from the premotor and parietal cortex. We found that the initial response to a grasp instruction was specific to the required movement, but not to the preparation time, reflecting required movement selection. However, when more preparation time was given, neural activity achieved unique states that likely related to withholding movements and anticipation of movement, shedding light on the roles of the premotor and parietal cortex in grasp planning. PMID- 29798891 TI - Lrfn2-Mutant Mice Display Suppressed Synaptic Plasticity and Inhibitory Synapse Development and Abnormal Social Communication and Startle Response. AB - SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression was detected in both glutamatergic and GABAergic neurons and Lrfn2-/- CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2-/- pups separated from their mothers and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult male Lrfn2-/- mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.SIGNIFICANCE STATEMENT Synaptic adhesion molecules regulate synapse development and function, which govern neural circuit and brain functions. The SALM/LRFN (synaptic adhesion-like molecule/leucine rich repeat and fibronectin type III domain containing) family of synaptic adhesion proteins consists of five known members for which the in vivo functions are largely unknown. Here, we characterized mice lacking SALM1/LRFN2 (SALM1 KO) known to associate with NMDA receptors (NMDARs) and found that these mice showed altered NMDAR-dependent synaptic transmission and plasticity, as expected, but unexpectedly also exhibited suppressed inhibitory synapse development and synaptic transmission. Behaviorally, SALM1 KO pups showed suppressed ultrasonic vocalization upon separation from their mothers and SALM1 KO adults showed enhanced responses to loud acoustic stimuli. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, social communication, and acoustic startle behavior. PMID- 29798894 TI - Kir2.1 & Nav1.5 in Sickness and in Health: Who Needs a Chaperone When They Have an Alpha Partner? PMID- 29798896 TI - Glycomics and Cardiovascular Disease: Advancing Down the Path Towards Precision. PMID- 29798895 TI - Cross Talk Between S-Nitrosylation and Phosphorylation Involving Kinases and Nitrosylases. PMID- 29798898 TI - Joshua Mayourian: Rising to the Challenge. PMID- 29798897 TI - Predictive Value of Circulating Progenitor Cells in Acute Coronary Syndrome: Implications for Treatment. PMID- 29798899 TI - Reverse Translation: Using Computational Modeling to Enhance Translational Research. PMID- 29798900 TI - von Willebrand Factor for Aortic Valve Intervention: From Bench to Real-Time Bedside Assessment. PMID- 29798890 TI - Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences. AB - Neocortical pyramidal neurons with somata in layers 5 and 6 are among the most visually striking and enigmatic neurons in the brain. These deep-layer pyramidal neurons (DLPNs) integrate a plethora of cortical and extracortical synaptic inputs along their impressive dendritic arbors. The pattern of cortical output to both local and long-distance targets is sculpted by the unique physiological properties of specific DLPN subpopulations. Here we revisit two broad DLPN subpopulations: those that send their axons within the telencephalon (intratelencephalic neurons) and those that project to additional target areas outside the telencephalon (extratelencephalic neurons). While neuroscientists across many subdisciplines have characterized the intrinsic and synaptic physiological properties of DLPN subpopulations, our increasing ability to selectively target and manipulate these output neuron subtypes advances our understanding of their distinct functional contributions. This Viewpoints article summarizes our current knowledge about DLPNs and highlights recent work elucidating the functional differences between DLPN subpopulations. PMID- 29798904 TI - Letter by Angus and Wright Regarding Article, "Pannexin-1 Channels as an Unexpected New Target of the Antihypertensive Drug Spironolactone". PMID- 29798901 TI - Steroid Hormone Vitamin D: Implications for Cardiovascular Disease. AB - Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations. PMID- 29798906 TI - Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients. AB - Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as a DNA damage sensitizer and cytotoxic agent. A phase I study of AZD1775 for solid tumors suggested activity against brain tumors, but a preclinical study indicated minimal blood-brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics and pharmacodynamics of AZD1775 in patients with first-recurrence, glioblastoma.Patients and Methods: Twenty adult patients received a single dose of AZD1775 prior to tumor resection and enrolled in either a dose-escalation arm or a time-escalation arm. Sparse pharmacokinetic blood samples were collected, and contrast-enhancing tumor samples were collected intraoperatively. AZD1775 total and unbound concentrations were determined by a validated LC/MS-MS method. Population pharmacokinetic analysis was performed to characterize AZD1775 plasma pharmacokinetic profiles. Pharmacodynamic endpoints were compared to matched archival tissue.Results: The AZD1775 plasma concentration-time profile following a single oral dose in patients with glioblastoma was well-described by a one-compartment model. Glomerular filtration rate was identified as a significant covariate on AZD1775 apparent clearance. AZD1775 showed good brain tumor penetration, with a median unbound tumor-to plasma concentration ratio of 3.2, and achieved potential pharmacologically active tumor concentrations. Wee1 pathway suppression was inferred by abrogation of G2 arrest, intensified double-strand DNA breakage, and programmed cell death. No drug-related adverse events were associated with this study.Conclusions: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent glioblastoma indicates good human brain tumor penetration, provides the first evidence of clinical biological activity in human glioblastoma, and confirms the utility of phase 0 trials as part of an accelerated paradigm for drug development in patients with glioma. Clin Cancer Res; 24(16); 3820-8. (c)2018 AACRSee related commentary by Vogelbaum, p. 3790. PMID- 29798907 TI - Targeted Therapies for Brain Tumors: Will They Ever Deliver? AB - The strategy of using biologically targeted therapeutics for cancer has yet to translate into effective treatment of gliomas. The neuro-oncology community is beginning to recognize that phase 0 studies should be performed to account for the impact of the blood-brain barrier on the ability of a therapeutic to reach its target(s). Clin Cancer Res; 24(16); 3790-1. (c)2018 AACRSee related article by Sanai et al., p. 3820. PMID- 29798905 TI - Response by Good et al to Letter Regarding Article, "Pannexin-1 Channels as an Unexpected New Target of the Antihypertensive Drug Spironolactone". PMID- 29798908 TI - Ad5NULL-A20: A Tropism-Modified, alphavbeta6 Integrin-Selective Oncolytic Adenovirus for Epithelial Ovarian Cancer Therapies. AB - Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for the manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumor selective virotherapy targeted to alphavbeta6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but nondetectable in healthy tissues.Experimental Design: Ad5NULL-A20 harbors mutations in each major capsid protein to preclude uptake via all native pathways. Tumor-tropism via alphavbeta6 targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed.Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), alphavbeta3/5 integrins, and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced alphavbeta6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of preexisting anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non-tumor-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared with Ad5. Tumor uptake, transgene expression, and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20-treated animals demonstrated significantly improved survival compared with those treated with oncolytic Ad5.Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of alphavbeta6-overexpressing cancers and exciting platforms for tumor-selective overexpression of therapeutic anticancer modalities, including immune checkpoint inhibitors. Clin Cancer Res; 24(17); 4215-24. (c)2018 AACR. PMID- 29798909 TI - Tumor Elastography and Its Association with Collagen and the Tumor Microenvironment. AB - Purpose: The tumor microenvironment presents with altered extracellular matrix (ECM) and stroma composition, which may affect treatment efficacy and contribute to tissue stiffness. Ultrasound (US) elastography can visualize and quantify tissue stiffness noninvasively. However, the contributions of ECM and stromal components to stiffness are poorly understood. We therefore set out to quantify ECM and stroma density and their relation to tumor stiffness.Experimental Design: A modified clinical ultrasound system was used to measure tumor stiffness and perfusion during tumor growth in preclinical tumor models. In vivo measurements were compared with collagen mass spectroscopy and automatic analysis of matrix and stromal markers derived from immunofluorescence images.Results: US elastography estimates of tumor stiffness were positively correlated with tumor volume in collagen and myofibroblast-rich tumors, while no correlations were found for tumors with low collagen and myofibroblast content. US elastography measurements were strongly correlated with ex vivo mechanical testing and mass spectroscopy-based measurements of total collagen and immature collagen crosslinks. Registration of ultrasound and confocal microscopy data showed strong correlations between blood vessel density and T-cell density in syngeneic tumors, while no correlations were found for genetic tumor models. In contrast to collagen density, which was positively correlated with stiffness, no significant correlations were observed for hyaluronic acid density. Finally, localized delivery of collagenase led to a significant reduction in tumor stiffness without changes in perfusion 24 hours after treatment.Conclusions: US elastography can be used as a potential biomarker to assess changes in the tumor microenvironment, particularly changes affecting the ECM. Clin Cancer Res; 24(18); 4455-67. (c)2018 AACR. PMID- 29798902 TI - Epigenomes in Cardiovascular Disease. AB - If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies. PMID- 29798910 TI - Draft Genome Sequence of the Feruloyl Esterase-Producing Strain Lactobacillus fermentum CRL1446, a Probiotic for Malnutrition. AB - We report here the draft genome sequence of Lactobacillus fermentum CRL1446 (2,148,781 bp, 51.4% G+C content). This strain exhibits feruloyl esterase activity and important technological and probiotic properties. Because of its proven beneficial effects in vivo, it represents an interesting candidate for the development of functional foods or pharmabiotics for malnutrition. PMID- 29798903 TI - Role of Resident Stem Cells in Vessel Formation and Arteriosclerosis. AB - Vascular, resident stem cells are present in all 3 layers of the vessel wall; they play a role in vascular formation under physiological conditions and in remodeling in pathological situations. Throughout development and adult early life, resident stem cells participate in vessel formation through vasculogenesis and angiogenesis. In adults, the vascular stem cells are mostly quiescent in their niches but can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. However, delineation of the characteristics and of the migration and differentiation behaviors of these stem cells is an area of ongoing investigation. A set of genetic mouse models for cell lineage tracing has been developed to specifically address the nature of these cells and both migration and differentiation processes during physiological angiogenesis and in vascular diseases. This review summarizes the current knowledge on resident stem cells, which has become more defined and refined in vascular biology research, thus contributing to the development of new potential therapeutic strategies to promote endothelial regeneration and ameliorate vascular disease development. PMID- 29798911 TI - Draft Genome Sequence of Rhizobium sophoriradicis H4, a Nitrogen-Fixing Bacterium Associated with the Leguminous Plant Phaseolus vulgaris on the Coast of Peru. AB - The genome sequence of Rhizobium sophoriradicis H4, a nitrogen-fixing bacterium isolated from the common bean (Phaseolus vulgaris) in Peru, is reported here. The genome assembly revealed a 6.44-Mbp genome which was distributed into 95 contigs, with N50 and L50 values of 293 kbp and 9, respectively. The genome contained 6,312 coding sequence (CDS) genes and 52 RNA genes (49 tRNAs and 3 rRNAs). PMID- 29798912 TI - Draft Genome Sequence of Bacillus velezensis PEBA20, a Strain with a Plant Growth Promoting Effect and Biocontrol Potential. AB - Bacillus velezensis PEBA20 is a poplar endophyte with biocontrol activities and plant growth-promoting effects. The genome of B. velezensis PEBA20 was sequenced and the draft genome assembled, with a length of 4,249,176 bp and 4,487 genes. PMID- 29798913 TI - Metagenomic Description of Preenrichment and Postenrichment of Recalled Chapati Atta Flour Using a Shotgun Sequencing Approach. AB - The bacterial microbiome of flour recalled for possible Escherichia coli O121 contamination was characterized before (hour 0) and after (hour 24) enrichment using shotgun sequencing. At hour 0, Staphylococcus (46.8 to 66.5%) and Pantoea (12.6 to 21.0%) bacteria were dominant. At hour 24, Enterobacter (28.7 to 70.9%) and Klebsiella (25.6 to 68.6%) bacteria dominated, and Escherichia coli ranged from 0.3 to 17.9%. PMID- 29798914 TI - Genome Sequence of JangDynasty, a Newly Isolated Mycobacteriophage. AB - JangDynasty is a bacteriophage that infects Mycobacterium smegmatis mc2155. It has a genome length of 70,883 bp, with 124 predicted open reading frames (ORFs), 42 of which have known functions. JangDynasty belongs to cluster O, and like other cluster O phages, it is a siphovirus with a prolate capsid. PMID- 29798915 TI - Genome Sequence of Geothermobacter sp. Strain HR-1, an Iron Reducer from the Lo'ihi Seamount, Hawai'i. AB - Geothermobacter sp. strain HR-1 was isolated from the Lo'ihi Seamount vent system in the Pacific Ocean at a depth of 1,000 m. Reported here is its 3.84-Mb genome sequence. PMID- 29798916 TI - Genome Sequence of PM2-Like Phage Cr39582, Induced from a Pseudoalteromonas sp. Isolated from the Gut of Ciona robusta. AB - Phage Cr39582 was induced by mitomycin C from Pseudoalteromonas sp. strain Cr6751, isolated from a marine invertebrate gut. Pseudoalteromonas phage Cr39582 has 85% pairwise nucleotide identity with phage PM2 but lacks sequence homology in the spike protein. This report supports previous bioinformatic identification of corticoviral sequences within aquatic bacterial genomes. PMID- 29798917 TI - Complete Genome Sequences of Two Salmonella Viruses, VSe11 and VSe102 (Family Myoviridae, Subfamily Ounavirinae), with a Very High Degree of Similarity. AB - Two lytic double-stranded DNA bacteriophages, VSe11 and VSe102, infecting broad spectrum Salmonella enterica were isolated from the sewage of two different poultry farms. The phage genomes comprise 86,360 bp and 86,365 bp, respectively, with a G+C content of 39.0%, and both contain 129 putative coding sequences. PMID- 29798918 TI - Draft Genome Sequence of the Plant Growth-Promoting Sphingobium sp. Strain AEW4, Isolated from the Rhizosphere of the Beachgrass Ammophila breviligulata. AB - Sphingobium sp. strain AEW4 is a novel isolate from rhizosphere soil attached to the root of the American beachgrass Ammophila breviligulata The genomic sequence consisted of 4,678,518 bp and 4,428 protein-coding sequences. Here we report the draft genome sequence of this strain and some initial insights on its plant growth-promoting capabilities. PMID- 29798919 TI - Complete Genome Sequencing of the Mouse Intestinal Isolate Escherichia coli Mt1B1. AB - Escherichia coli Mt1B1, a mouse isolate, is a facultative anaerobic bacterium which was shown to counteract Salmonella enterica serovar Typhimurium infection in a mouse model. In the present study, we describe the complete genome sequence of E. coli Mt1B1, composed of a 5.1-Mb chromosome and a 62.6-kb plasmid. PMID- 29798920 TI - Complete Genome Sequence of Escherichia coli J53, an Azide-Resistant Laboratory Strain Used for Conjugation Experiments. AB - We report here the complete genome sequence of Escherichia coli J53, which is used as a recipient in conjugation experiments and is a laboratory strain derived from E. coli K-12. This genome sequence will help in the development of a comprehensive genetic analysis of conjugative elements. PMID- 29798921 TI - Complete Genome Sequence of Streptomyces lunaelactis MM109T, Isolated from Cave Moonmilk Deposits. AB - Streptomyces lunaelactis MM109T is a ferroverdin A (anticholesterol) producer isolated from cave moonmilk deposits. The complete genome sequence of MM109T was obtained by combining Oxford Nanopore MinION and Illumina HiSeq and MiSeq technologies, revealing an 8.4-Mb linear chromosome and two plasmids, pSLUN1 (127,264 bp, linear) and pSLUN2 (46,827 bp, circular). PMID- 29798922 TI - Draft Genome Sequence of Two Marine Plantactinospora spp. from the Gulf of California. AB - Plantactinospora sp. strains BB1 and BC1 were isolated in 2009 from sediment samples of the Gulf of California from among almost 300 actinobacteria. Genome mining of their ~8.5-Mb sequences showed the bioprospecting potential of these rare actinomycetes, providing an insight to their ecological and biotechnological importance. PMID- 29798923 TI - Single Passage of Human Metapneumovirus in LLC-MK2 Cells Does Not Affect Viral Protein-Coding Capacity. AB - Here, we report the complete genome sequences of human metapneumovirus (HMPV) prior to and after passaging in LLC-MK2 cells. Paired comparisons of the 13,335 nucleotide genomes revealed that the virus acquired the T10736C transition in its genome, which did not affect the amino acid sequences of HMPV proteins. PMID- 29798924 TI - Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient. AB - Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The blaKPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing. PMID- 29798925 TI - Complete Genome Sequence of Buffalopox Virus. AB - The first complete genome assembly of buffalopox virus isolate Karachi 2005, with a length of 195,630 bp, is presented here. Phylogenetic analysis shows the virus to cluster within Vaccinia species, and the genome contains 177 protein-coding sequences. PMID- 29798926 TI - Draft Genome Sequences of Enterococcus mundtii Strains Isolated from Beef Slaughterhouses in Kenya. AB - We present here draft genome sequences of Enterococcus mundtii strains K7-EM, P2 EM, C11-EM, and H18-EM, which were isolated from slaughterhouse equipment, carcasses, and personnel of small- and medium-sized beef slaughterhouses in Kenya. PMID- 29798927 TI - Draft Genome Sequence of Mycobacterium montefiorense Isolated from Japanese Black Salamander (Hynobius nigrescens). AB - Mycobacterium montefiorense is a member of the Mycobacterium simiae complex, the largest group of nontuberculous mycobacteria. Here, we report the genome sequence of M. montefiorense isolate BS, isolated from diseased Japanese black salamander (Hynobius nigrescens) reared in an aquarium in Japan. This is the first reported case of an M. montefiorense infection in an amphibian. PMID- 29798928 TI - Draft Genomic Sequencing of Six Potential Extraintestinal Pathogenic Escherichia coli Isolates from Retail Chicken Meat. AB - Potential extraintestinal pathogenic Escherichia coli strains DP254, WH333, WH398, F356, FEX675, and FEX725 were isolated from retail chicken meat products. Here, we report the draft genome sequences for these six E. coli isolates, which are currently being used in food safety research. PMID- 29798929 TI - Complete Genome Sequences of Four Novel Human Coronavirus OC43 Isolates Associated with Severe Acute Respiratory Infection. AB - We report here the complete genome sequences of four human coronavirus (HCoV) OC43 isolates generated using targeted viral nucleic acid capture and next generation sequencing; the isolates were collected in New Mexico and Arkansas, USA, in February (HCoV-OC43/USA/TCNP_0070/2016) and March (HCoV OC43/USA/ACRI_0052/2016) 2016 and January 2017 (HCoV-OC43/USA/TCNP_00204/2017 and HCoV-OC43/USA/TCNP_00212/2017). PMID- 29798931 TI - Correction for Smith and Unckless, "Draft Genome Sequence of Lysinibacillus fusiformis Strain Juneja, a Laboratory-Derived Pathogen of Drosophila melanogaster". PMID- 29798930 TI - High-Quality Draft Genome Sequence of Sphaerisporangium cinnabarinum ATCC 31213. AB - A high-quality draft genome sequence of Sphaerisporangium cinnabarinum ATCC 31213 is presented here. This bacterium produces several important bioactive compounds and may also produce functional amyloids. This is the first sequenced genome from the genus Sphaerisporangium, and it will be essential in determining the nature of the potential amyloid protein. PMID- 29798932 TI - High-throughput fabrication of vascularized spheroids for bioprinting. AB - Overcoming the problem of vascularization remains the main challenge in the field of tissue engineering. As three-dimensional (3D) bioprinting is the rising technique for the fabrication of large tissue constructs, small prevascularized building blocks were generated that can be incorporated throughout a printed construct, answering the need for a microvasculature within the small micron range (<10 MUm). Uniform spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. Since monoculture spheroids of endothelial cells were unable to remain stable, coculture spheroids combining endothelial cells with fibroblasts and/or adipose tissue derived mesenchymal stem cells (ADSC) as supporting cells, were created. When applying the favorable coculture ratio, viable spheroids were obtained and endothelial cells spontaneously formed a capillary-like network and lumina, as shown by immunohistochemistry and transmission electron microscopy. Especially the presence of ADSC led to a higher vascularization and extracellular matrix production of the microtissue. Moreover, spheroids were able to assemble at random in suspension and in a hydrogel, creating a macrotissue. During at random assembly, cells reorganized, creating a branched capillary-network throughout the entire fused construct by inoculating with capillaries of adjacent spheroids. Combining the advantage of this natural capacity of microtissues to self-assemble and the controlled organization by bioprinting technologies, these prevascularized spheroids can be useful as building blocks for the engineering of large vascularized 3D tissues. PMID- 29798933 TI - Nanopatterning by ion beam sputtering in unconventional formats. AB - Nanopatterning at solid surfaces by ion beam sputtering (IBS) has been practiced mostly for stationary substrates with an ion beam incident under a fixed sputter geometry. We have released such constraints in the sputter condition. We simultaneously apply two ion beams or sequentially vary the orientation of substrate with respect to an ion beam. We also periodically change either the azimuthal or polar angle of the substrate with respect to an ion beam during IBS. These unconventional ways of IBS can improve the order of the pattern, and produce novel and non trivial nano patterns that well serve as touch stones to refine the theoretical models and thus deepen our understanding of the patterning mechanisms by IBS. PMID- 29798934 TI - Nanoformulations of doxorubicin: how far have we come and where do we go from here? AB - Nanotechnology, focused on discovery and development of new pharmaceutical products is known as nanopharmacology, and one research area this branch is engaged in are nanopharmaceuticals. The importance of being nano has been particularly emphasized in scientific areas dealing with nanomedicine and nanopharmaceuticals. Nanopharmaceuticals, their routes of administration, obstacles and solutions concerning their improved application and enhanced efficacy have been briefly yet comprehensively described. Cancer is one of the leading causes of death worldwide and evergrowing number of scientific research on the topic only confirms that the needs have not been completed yet and that there is a wide platform for improvement. This is undoubtedly true for nanoformulations of an anticancer drug doxorubicin, where various nanocarrriers were given an important role to reduce the drug toxicity, while the efficacy of the drug was supposed to be retained or preferably enhanced. Therefore, we present an interdisciplinary comprehensive overview of interdisciplinary nature on nanopharmaceuticals based on doxorubicin and its nanoformulations with valuable information concerning trends, obstacles and prospective of nanopharmaceuticals development, mode of activity of sole drug doxorubicin and its nanoformulations based on different nanocarriers, their brief descriptions of biological activity through assessing in vitro and in vivo behavior. PMID- 29798935 TI - Influence of temperature on the magnetic oscillations in graphene with spin splitting: a new approach. AB - We analyze the magnetic oscillations (MO) due to the de Haas-van Alphen effect, in pristine graphene under a perpendicular magnetic field, taking into account the Zeeman effect. We consider a constant Fermi energy, such that the valence band is always full and only the conduction band is available. At zero temperature the MO consist of two sawtooth peaks, one for each spin. Both peaks have the same frequency, but different amplitude and phase. We show that, in order to observe the spin splitting in the MO, Fermi energy of about 0.1 eV is required. At low temperatures we obtain that the MO can be expressed as the MO at zero temperature, plus small Fermi-Dirac like functions, each centered around the MO peaks. Using this expression, we show that the spin splitting is observable in the MO only when the thermal energy is smaller than the Zeeman energy. We also analyze the shift of the MO extrema as the temperature increases. We show that it depends on the magnetic field, which implies a broken periodicity at nonzero temperature. Finally, we obtain an analytical expression for the MO envelope. The results obtained could be used to infer temperature changes from the MO extrema shift and vice versa. PMID- 29798936 TI - Rapid response of Kasabach-Meritt phenomenon to a combination of oral prednisolone and sirolimus. PMID- 29798937 TI - Plica polonica: from national plague to death of the disease in the nineteenth century Vilnius. PMID- 29798940 TI - Stent removal using novel balloon catheter after rupture of stent for EUS-guided pancreatic duct drainage. PMID- 29798939 TI - Identification of a novel mutation in the SRD5A2 gene of one patient with 46,XY disorder of sex development. PMID- 29798938 TI - Sperm origins and concentration do not impact the clinical outcomes in intracytoplasmic sperm injection cycles. AB - In the present study, we evaluated the impact of sperm origins and concentration on the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles. A total of 1201 ICSI cycles were retrospectively analyzed for male azoospermia or oligozoospermia between January 2015 and December 2015 in the Peking University Third Hospital. Patients were divided into three groups (Group 1 vs Group 2/3; surgically extracted sperm vs ejaculated sperms): Group 1 included 343 ICSI cycles and Group 2 analyzed 388 cycles on semen with sperm concentration <5 * 106 ml-1 (severe oligozoospermia group). Group 3 included 470 cycles with sperm concentration between 5 * 106 ml-1 and 15 * 106 ml-1 (mild oligozoospermia group). Fertilization rates, clinical pregnancy rates, and live birth rates were analyzed and compared among groups of different semen origins and concentrations on the oocyte retrieval day. Group 2 showed a lower fertilization rate than Group 3 (62.9% +/- 21.6% vs 66.8% +/- 22.1%,P< 0.05). There were no statistically significant differences in clinical pregnancy rate per transfer (51.3%, 46.7%, and 50.0%, respectively), live birth rate per transfer (44.4%, 40.9%, and 41.4%, respectively), accumulative live birth rate (58.3%, 51.0%, and 52.1%, respectively), twin birth rate (18.4%, 10.6%, and 12.6%, respectively), and birth defects rate (0, 0.3%, and 0.2%, respectively) among three groups. The results of this study indicated that sperm origins and concentration do not impact the clinical outcomes in ICSI cycles. PMID- 29798941 TI - Cystic duct antegrade stenting for cholangitis after the long-term deployment of lumen-apposing metal stents for calculous cholecystitis. PMID- 29798943 TI - Colorectal cancer: A looming threat, opportunities, and challenges for the Saudi population and its healthcare system. PMID- 29798942 TI - Clinical and prognostic significance of MUC1 expression in patients with esophageal squamous cell carcinoma after radical resection. AB - Background/Aim: To investigate the clinical and prognostic significance of MUC1 expression in patients with esophageal squamous cell carcinoma (ESCC) after radical resection. Materials and Methods: A total of 108 ESCC specimens were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1 at the mRNA level and were evaluated by immunohistochemistry (IHC) to detect MUC1 at the protein level. Results: MUC1 mRNA was found in 74 cases by RT-PCR and MUC1 protein expression was found by IHC in 70 cases. Both MUC1 mRNA and protein expression correlated with pT (<0.05), pN (P < 0.01), and pTNM (<0.01). The 5 year survival rates of the patients were 39.8%. In univariate analysis, the 5 year survival rate in the ESCC patients was significantly associated with pT (P < 0.01), pN (P < 0.01), pTNM stage (P < 0.01), and MUC1 mRNA and protein expression (P < 0.05). In multivariate analysis, pN and MUC1 expression were the independent relevant factors. Conclusion: MUC1 expression can become a useful marker to predict poor prognostic factors for 5-year survival rate in patients with ESCC after radical resection. PMID- 29798944 TI - Papillary thyroid cancer: Why the increase and what can be done? PMID- 29798945 TI - Radical radiotherapy for carcinoma of the larynx in the elderly: Functional and oncological outcomes from a tertiary cancer care center in India. AB - INTRODUCTION: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes. MATERIALS AND METHODS: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test. RESULTS: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%. CONCLUSION: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age. PMID- 29798946 TI - Prevalence of human papillomavirus in oral squamous cell carcinoma: A rural teaching hospital-based cross-sectional study. AB - BACKGROUND: Human papillomavirus (HPV) is a well-established oncogenic agent in the pathogenesis of cervical carcinoma. Its role in the oncogenesis of tumors such as oral squamous cell carcinoma (OSCC) is not clear. Globally, approximately 3% of OSCCs are positive for HPV. Studies conducted in India indicate its prevalence from as low as 0% to as high as 74%. However, a recent Indian study on leukoplakia failed to find any evidence of HPV involvement. This motivated us to reexamine the HPV status in OSCC. AIM: To evaluate the prevalence of HPV in OSCC. SETTINGS AND DESIGN: This was a rural teaching hospital-based cross-sectional study. SUBJECTS AND METHODS: Sixty histopathologically confirmed samples of OSCC were used for the study. Genomic DNA was isolated from frozen, surgically resected specimens. HPV positivity was tested by polymerase chain reaction-based method using GP5+/6+ primers in the L1 consensus region of the viral genome. RESULTS: None of the samples were HPV positive. CONCLUSIONS: Results of this study indicate that the association between HPV and OSCC may be overestimated. Hence, multicentric studies covering diverse geographical and socioeconomic groups are needed to delineate the profile of HPV infectivity and OSCC in the Indian subcontinent. PMID- 29798947 TI - Nasopharyngeal carcinoma: Experience and treatment outcome with radical conformal radiotherapy from a tertiary care center in India. AB - BACKGROUND AND AIM: The majority of nasopharyngeal carcinoma (NPC) reports on the outcome and prognostic factors are from endemic high-risk regions. Data on the outcome of Indian patients are sparse. In this study, we retrospectively analyzed the outcome of NPC patients treated radically with conformal radiotherapy (RT). The primary objective was to assess the outcome, and the secondary objectives were to assess treatment-related morbidities and the impact of various prognostic factors on the outcome. MATERIALS AND METHODS: Sixty-eight patients with biopsy proven NPC who received radical conformal RT, i.e., three-dimensional conformal RT or intensity-modulated RT (IMRT) during 2004-2013 were analyzed. All patients received conformal RT with or without chemotherapy. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS, version 20.0) software, IBM, USA. Survival analysis was performed using Kaplan-Meier method. For calculating the hazard ratio of the prognostic factors, univariate and multivariate Cox regression analyses were done. Chi-square test was used to determine the association. RESULTS: In this study, with a median follow-up of 43 months, the overall survival (OS), disease-free survival, and cause-specific survival were 91, 85.2, and 98.4% at 2 years and 78.3, 72.8, and 88.2% at 3 years, respectively. The locoregional failure was low (3%), and the 5-year cause specific survival with chemoradiation was excellent (79%), even with 50% of the patients being nonmetastatic Stage IV. Eleven out of 12 failures were distant metastases. The treatment-related late morbidities were acceptable and better with IMRT. Significant prognostic factors affecting the outcome were composite stage of the disease and the interval between diagnosis and treatment initiation. CONCLUSION: In locally-advanced NPC, excellent local control is possible with modern conformal RT with concurrent chemotherapy. Distant metastases remain a therapeutic challenge despite systemic chemotherapy. Novel systemic therapies are needed in the future for improving the OS of these patients. PMID- 29798948 TI - Magnetic resonance imaging: A predictor of pathological tumor dimensions in carcinoma of anterior two-thirds of tongue - A prospective evaluation. AB - INTRODUCTION: Preoperative imaging is mandatory for deciding the extent of surgery in tumors of oral tongue. Previous studies have shown the significance of depth of tumor invasion in predicting nodal involvement. AIM: This prospective study aimed to assess the correlation between tumor dimensions in all three planes obtained through preoperative imaging and histopathological findings, as well as the correlation between these and pathological node positivity. MATERIALS AND METHODS: Fifty-nine consecutive patients with nonmetastatic, operable, squamous cell carcinoma of anterior two-thirds of the tongue were included in the study. Preoperative imaging findings were compared with pathological findings and analyzed. RESULTS: Histopathological dimensions were concordant with imaging findings. Anteroposterior, transverse, and craniocaudal (CC) dimensions obtained through imaging showed a significant correlation with corresponding pathological findings (0.730, 0.621, 0.810, respectively; P < 0.001). Among all three, only CC dimension showed a significant correlation with pathological nodal involvement (odds ratio [OR] = 7.875, P = 0.03, relative risk = 0.236). Pathological tumor thickness of >3 mm had a positive predictive value of 54.9% for nodal involvement (OR = 7.875, P = 0.03). CONCLUSION: With widespread availability of state-of-the art magnetic resonance (MR) scanners, CC dimension needs to be emphasized as the most significant prognostic tumor parameter. Recent evidence, including our study, suggests that MR imaging is concordant with pathological findings, justifying its use in the pretreatment evaluation of oral tongue lesions. PMID- 29798949 TI - Clinicopathological profile of papillary carcinoma of thyroid: A 10-year experience in a tertiary care institute in North Karnataka, India. AB - CONTEXT: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy accounting for 80% of the thyroid cancers. Many histopathologic variants of PTC have been recognized, and few of these are of prognostic significance. The studies on clinicopathological features of PTC and its variants are so far seldom reported in India. AIM: The aim of the study was to study the percentage distribution of PTC among total thyroid specimens, the age and sex distribution of PTC, its histopathological features including frequency of nuclear findings, and various histological subtypes are also studied in detail. Methods: All cases of PTC diagnosed in our department from April 2003 to March 2013 formed the material for the study. The tissues were routinely processed and stained. On microscopic examination, tumors were classified according to 2004 WHO classification. RESULTS: PTC formed the predominant type of malignancy accounting to 71% of the total cases. Of these, about 75% of patients were in the second to fifth decade. Male to female ratio was 1:5.4. Other than the usual classic variant and follicular variant, we also found rare types such as clear cell variant, tall cell type, oncocytic type, and macrofollicular variant. Microscopically, nuclear overcrowding and ground glass nuclei were seen in more than 90% of cases. Nodular goiter, Hashimoto's thyroiditis, and follicular adenoma were associated lesions in some cases. CONCLUSION: PTC is the most common thyroid malignancy, and it can affect any age group though it presents mostly in the third to fourth decade of life. Recognition of histological subtype is crucial in patient prognosis. PMID- 29798950 TI - Compliance and outcomes of concurrent Chemo-radiation in patients with peri ampullary cancer undergoing curative resections. AB - OBJECTIVES: We aimed to study the compliance and treatment outcome of patients who received adjuvant treatment following curative resection for periampullary cancers periampullary cancers. MATERIALS AND METHODS: Institute medical records of PAC treated during 2007-2014 were retrieved. Demographics, treatment, and outcome in patients who were intended to receive adjuvant chemoradiation after curative resection were analyzed. Patients received first cycle chemotherapy with 5-fluorouracil folinic acid/capecitabine, followed by external radiotherapy 45 Gy/25 fractions/5 weeks and second and third cycle concurrent chemotherapy. Fourth and fifth cycle chemotherapy were administered after radiotherapy). Various prognostic factors, disease-free survival (DFS), and overall survival (OS) were evaluated. RESULTS: Sixty-five patients were evaluated. Median age was 50 years. 96.9% patients completed the intended course of radiation and overall adherence to chemotherapy was 86.2%. Median follow-up and DFS were 20 and 29.64 months, respectively (range: 1.9-97.3 months). Estimated 1-, 2-, 5-year DFS was 77.8%, 59.3%, and 37.6%, respectively. One-year estimated OS was 92.7%. Median DFS for node-negative and node-positive patients was 88.6 and 24.33 months (P = 0.06). Grade >=III hematological toxicity was 20%. CONCLUSION: Positive node indicated a trend toward poor survival. The study highlights high compliance to multimodal management of PAC with acceptable toxicity in and out of clinical trial setting in a tertiary cancer center in India. PMID- 29798951 TI - Advanced hepatocellular carcinoma: A regional cancer center experience of 48 cases. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a major health burden and the seventh most common cause of cancer-related death in India. Patients with advanced unresectable HCC have a poor prognosis with a reported median survival of only 2-3 months with the best supportive care (BSC). Sorafenib is the only drug that has demonstrated a survival benefit over BSC in advanced HCC. Unfortunately, even though it has been used for a long time, there are very few published data regarding the experience of sorafenib therapy in advanced HCC from India. MATERIALS AND METHODS: Patients diagnosed with advanced HCC from January 2012 to July 2017 at our center were reviewed retrospectively. Patients' profile, time to progression, survival, and toxicity of sorafenib therapy were evaluated. RESULTS: Of the 48 advanced patients with HCC, 35 (72.9%) were male. The median age at diagnosis was 52 years. The most common presenting symptom was abdominal pain (77%, n = 37), followed by abdominal distension (37.5%, n = 18), loss of appetite and/or weight (33.3%, n = 16), and jaundice (16.7%, n = 8). Hepatitis B virus infection was documented in 37 patients (77%), whereas 4 patients had hepatitis C virus infection. Patients were treated with standard dose sorafenib (n = 30), BSC alone (n = 14), or transarterial chemoembolization followed by sorafenib (n = 4). Sorafenib therapy was well-tolerated in most cases. The median progression-free survival with upfront sorafenib was 4.3 months. The median overall survival (OS) of the patients who received upfront sorafenib was significantly better than those treated with BSC alone (5.9 vs 3.0 months; log rank P= 0.00). CONCLUSION: Sorafenib therapy was well-tolerated and provided about 3 months longer median OS in our patients with advanced HCC than those treated with BSC alone. PMID- 29798952 TI - Nontrial, real-world outcomes in unresectable locally advanced pancreatic cancer: Chemotherapy and chemoradiation is the standard while surgery is uncommon. AB - BACKGROUND: Outcomes and survival of truly unresectable locally advanced pancreatic cancers (LAPC) is often reported along with borderline resectable pancreatic cancers especially from a real world cohort. METHODS: The audit of LAPC patients, diagnosed based on the NCCN criteria between February 2013 and January 2016 was used to identify patients starting and continuing treatment in our institution. Practice patterns, outcomes and prognostic factors for overall survival were evaluated. RESULTS: Of the 83 patients, 52 were available for inclusion in the analysis. Median age was 56 years (range 30- 77), with males constituting 75% of patients. Baseline comorbidities seen were diabetes mellitus, hypertension and cardiac dysfunction in 46.1%, 69.1% and 52% of patients respectively. 84.6% of patients had arterial vascular involvement as criteria for unresectable LAPC. 50% of patients received chemotherapy only, while the remainder received chemotherapy and concurrent chemoradiation. One patient was able to undergo curative R0 resection. FOLFIRINOX was the most commonly used chemotherapy regimen (53.8%). With a median follow up of 15.9 months, median progression free survival (mPFS) was 7.26 months (95% CI: 5.75-8.76) and median OS was 11.8 months (95% CI: 9.96 - 13.61). None of the potential prognostic factors evaluated, i.e., age, gender, nodal status, pre-treatment CA 19.9 levels, showed correlation with OS. CONCLUSION: This analysis shows outcomes in unresectable LAPC comparable to existing literature. Surgery in unresectable LAPC patients is less common than seen in previously published studies, more likely due to this cohort being truly 'unresectable' in terms of major arterial involvement. PMID- 29798954 TI - Interneural tissue clearance in axillary dissection for breast cancer: What is the importance? AB - BACKGROUND: Breast cancer is the most common cancer in women and second most common type of cancer overall. The prime objectives of axillary surgery in the management of breast cancer are 1) accurate staging, 2) treatment to cure and 3) quantitative information of metastatic lymph nodes for prognostic purposes and allocation to adjuvant protocols. During axillary dissection, all 3 level lymphnodes are removed, while the important axillary structures (axillary vein, long thoracic and thoracodorsal nerves) are preserved. The latter two structures are particularly vulnerable to injury when dissecting the tissue between them (the interneural tissue). METHODS: This prospective non-randomized study, conducted on 125 female patients, who underwent axillary lymphadenectomy for breast cancer has evaluated the importance of dissection of the Interneural tissue during axillary dissection in breast cancer surgery by reviewing the lymph node yield and metastasis rate. The interneural tissue was excised separately after a routine axillary dissection. RESULTS: Lymph nodes were found in the interneural tissue of 70 out of 125 patients (56%). The average number of interneural lymph nodes recovered per specimen was 1.3. The interneural tissue lymph nodes were positive for metastasis in 10 (8%) patients. There was no incidence of isolated metastasis in the internerve tissue nodes. CONCLUSIONS: There is a significant incidence of lymph nodes (56%) and axillary node metastases (8%) in the tissue lying between the long thoracic and thoracodorsal nerves. Therefore, meticulous dissection and excision of this interneural tissue is strongly recommended to optimize decision making regarding adjuvant treatment and outcome. PMID- 29798955 TI - Axillary dissection for breast cancer using electrocautery versus ultrasonic dissectors: A prospective randomized study. AB - BACKGROUND: The major morbidities of modified radical mastectomy both short- and long-term are sequelae of axillary dissection. Flap complications, prolonged seroma, need for axillary drainage, wound infection, lymphedema, shoulder stiffness, and paresthesia are major causes for morbidity after axillary dissection. Different techniques have been implemented to tackle these problems. Few of these include reducing the axillary dead space, using various forms of energy devices. AIMS: We have prospectively compared two energy sources, namely, ultrasonic dissector (UD) against the electrocautery dissection in axillary dissection for breast cancer with respect to outcomes. MATERIALS AND METHODS: One hundred female patients with breast cancer undergoing modified radical mastectomy were randomized to either of the two arms - axillary dissection using UD and axillary dissection using electrocautery. The parameters taken into consideration were operating time, operative blood loss, amount and duration of axillary drainage, flap complications, nodal yield, and postoperative pain scoring. RESULTS: There were no significant differences overall between the two groups with respect to oncological safety and functional outcomes. PMID- 29798953 TI - Comparative pharmacokinetics, efficacy, and safety of bevacizumab biosimilar to reference bevacizumab in patients with metastatic colorectal cancer. AB - OBJECTIVE: To establish clinical biosimilarity of BevaciRelTM bevacizumab biosimilar (study bevacizumab) with the reference innovator bevacizumab in terms of pharmacokinetics, efficacy, and safety in metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A total of 119 patients with mCRC were enrolled across 20 centers and randomized to receive study and reference bevacizumab in this Phase III clinical study. Of these, 116 patients were administered bevacizumab 5 mg/kg intravenously every 2 weeks with folinic acid, fluorouracil, and irinotecan regimen. The primary endpoint of the study was objective response rate (ORR) at week 25, and the secondary endpoints assessed were progression-free survival (PFS), overall survival (OS), and assessment of pharmacokinetics and safety along with immunogenicity in both treatment arms. RESULTS: The ORR was 60.53% in study bevacizumab and 66.67% in reference arm. The proportions of subjects showing CR and PR were comparable in both the arms. The median PFS at 1 year was 3.83 months in test arm and 4.6 months in reference arm. The mean OS was 10.91 months in test arm and 14.68 months in reference arm. The difference in ORR, median PFS, and OS was not statistically significant (P > 0.05). The median Tmaxwas 6.00 h in both the arms. The median t1/2 was 330.63 h and 226.14 h, respectively, for test and reference bevacizumab. The adverse event profile of both products was in line with the known profile of bevacizumab. CONCLUSION: The study biosimilar bevacizumab was found to be noninferior and clinically biosimilar to the reference bevacizumab, thereby meeting an unmet medical alternative need in mCRC. PMID- 29798956 TI - Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung. AB - OBJECTIVE: To evaluate the short-term efficacy and safety of apatinib alone or combined with chemotherapy in the treatment of advanced squamous cell lung cancer. METHODS: Forty patients with advanced squamous cell lung carcinoma were enrolled in this study, who were treated in Xuzhou Central Hospital from 2014 to 2015. All patients underwent first-line or more chemotherapy. Patients were administrated with apatinib 425 mg/day, alone or combined with chemotherapy. The short-term efficacy was evaluated according to the RECIST criteria. The main safety event was evaluated by CTC-AE criteria. RESULTS: Among all the 40 patients, partial response in 5 cases, stable disease in 24 cases, progressive disease in 11 cases, overall response rate in 12.5%, disease control rate in 72.5%, the median progression-free survival was 3.7 months. The main adverse events were leukopenia, fatigue, and hypertension. Most of the adverse events were grade I and II level. CONCLUSION: The use of apatinib alone or combined with chemotherapy in patients with advanced or metastatic squamous cell lung carcinoma demonstrates a high response rate, favorable tolerability profile. PMID- 29798957 TI - Role of laparoscopy in predicting surgical outcomes in patients undergoing interval cytoreduction surgery for advanced ovarian carcinoma: A prospective validation study. AB - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopy in detecting inoperable disease in patients undergoing interval cytoreduction (ICR) for advanced ovarian carcinoma (AOC). The primary outcome measured was the performance of laparoscopy-based predictive index value (PIV) score developed by Fagotti et al. The secondary outcomes measured were performance of individual parameters included in PIV score and optimal cytoreduction (OCR) rates in our population. PATIENTS AND METHODS: This is a single-arm, prospective validation trial. Patients undergoing ICR for AOC in our institution were evaluated prospectively with laparoscopy before planned attempt at debulking surgery. Seven laparoscopic parameters included in laparoscopic PIV score were evaluated. Laparoscopic findings were compared with the final outcomes of definitive surgery. OCR was defined as residual disease <1 cm. The efficiency of the individual laparoscopy score was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 73 patients planned for ICR for AEOC were included in the study. Laparoscopic PIV score could successfully predict inoperability in 12 (16.4% of total study population) out of 14 inoperable patients in the total population and thus could avoid 85% of unsuccessful surgeries at a PIV score cutoff of >=8. Performance of individual parameters included in PIV score was also evaluated. Two parameters out of seven, that is, mesenteric retraction and stomach infiltration had poor performance on ROC curve. Modified PIV score was calculated for each patient after excluding these two parameters. Modified PIV score had similar performance as Fagotti's PIV score at cutoff >=6 (P = 0.728, for difference in area under the curve). No staging laparoscopy-related serious adverse events were noted in any of the patients. CONCLUSIONS: Laparoscopy is a safe, effective, and accurate method for predicting inoperability in patients undergoing ICR for AEOC. PMID- 29798958 TI - Primary neuroendocrine carcinoma of the thymus: A retrospective analysis from a regional cancer center in Western India. AB - Primary neuroendocrine tumors of the thymus are unusual anterior mediastinal tumors with a variable prognosis. A retrospective analysis of five patients with primary neuroendocrine tumors of the thymus admitted to the Gujarat Cancer and Research Institute, Ahmedabad, between 2012 and 2016, was done to study the clinical profile and outcome of these patients. The role of various prognostic factors such as surgical resection, histological grade, and Masaoka-Koga staging was also analyzed. Majority of the patients present with signs and symptoms related to a rapidly expanding mediastinal mass, such as breathlessness, facial puffiness, edema over the neck and extremities, chest pain, and other features of superior vena cava (SVC) syndrome. Collateral venous dilatation over the neck and chest and edema over neck were the most common physical signs. All the patients enrolled in the study presented in advanced stages with a poor differentiation on histopathological examination. Thymic neuroendocrine tumors usually manifest as large, lobulated, and locally invasive anterior mediastinal masses surrounding the great vessels of the neck and thorax. None of the diagnosed patients underwent surgical resection in view of extensive vascular encasement in the neck and thorax, and all of them were started on platinum-based palliative chemotherapy. The median survival of the patients was 12 months with the longest survival of 16 months for one patient. Possibility of this potentially rare entity should be kept in mind when a patient presents with features of SVC syndrome and large mediastinal mass. Complete surgical resection of the tumor is prognostic of improved treatment outcome and long-term survival. Large tumor size could be a determinant of poor overall outcome, and tumor size should strongly be considered as a factor in the revised (NETT) Neuroendocrine tumours of thymus staging. Histological grade and Masaoka-Koga stage are the important prognostic factors, but this study emphasizes the utmost need to further validate the prognostic factors. PMID- 29798959 TI - Quality assessment and improvement of cancer registration system in Kamrup Urban District: A report. AB - INTRODUCTION: The global burden of cancer incidence and mortality are rising continuously worldwide. As per the GLOBOCAN 2012 estimates, about 14.1 million cancer cases and 8.2 million cancer deaths occurred and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. Reliable data on the magnitude and the pattern of cancer are essential for monitoring the health of the community, assessing the performance of the health care system. Cancer registries should pay great attention to quality of their data. The completeness of cancer registry data- the extent to which all of the incident cancers occurring in the population are included in the registry database- is an extremely important attribute of a cancer registry. There are mainly four aspects influencing the quality of data namely, comparability, completeness, validity and timeliness. MATERIALS AND METHODS: Data regarding incidence and mortality with methods of diagnosis for individual years were obtained from the National Cancer Registry Program database of the Indian Council of Medical Research for 2009 to 2014 periods and recalculated for combined years (2009-2014). RESULTS: In males in 2009-11, 77.1% were microscopically confirmed cases which are improved in the later years and for the year 2012-2014, it is 81.4%. In females also the percentage of microscopically confirmed cases were increased from 80.2% to 82.9%. An improvement in mortality to incidence ratio was observed over the years. MI ratio in males was improved to 32.9%. for the year 2012-14 as compared to 28.6% for the year 2009-11 while in female MI ratio is also increased from 18.8% to 21.8% over the period from 2009-11 to 2012-14. Whereas DCO was decreased from 12% to 10.7% in males and 7.3% to 6.6% in females respectively from the period 2009 11 to 2012-14. CONCLUSION: Although there is a slight improvement in data quality till date, there is an enormous scope for population based cancer registry Guwahati to improve the data quality. PMID- 29798960 TI - Effect of levamisole on expression of CD138 and interleukin-6 in human multiple myeloma cell lines. AB - INTRODUCTION: Multiple myeloma (MM) is a B-cell malignancy accounting for 0.8% of all cancer deaths globally. This malignancy is characterized by lytic bone disease renal insufficiency, anemia, hypercalcemia, and immunodeficiency. The myeloma cells have enhanced expression of CD138. CD138 is a transmembrane heparin sulfate glycoprotein expressed on different types of adherent and nonadherent cells.CD138 is used as a standard marker for identification of tumor cells. AIMS AND OBJECTIVES: Despite introduction of many therapeutic agents, the management of multiple myeloma (MM) remains a challenge and search for new therapeutic agents is in progress. In this study, we attempted to evaluate the effect of an alkaline phosphatase inhibitor, levamisole on expression of CD138, and level of interleukin-6 (IL-6) in human MM cell lines RPMI 8226 and U266 B1. MATERIAL AND METHODS: U266B1 and RPMI 8226 cell lines were obtained from the National Centre for Cell Sciences, Pune. Alkaline phosphatase assay, Interleukin-6 assay and CD138 expression on myeloma cells by flow cytometry were investigated when the cells were exposed to Levamisole. RESULTS: Levamisole-mediated growth inhibition of myeloma cells in vitro is associated with a loss of CD138 and increased IL-6 secretion. The increased secretion of IL-6 by myeloma cells could be an attempt to protect themselves from apoptosis. CONCLUSION: Levamisole inhibited CD138 expression and affected the levels of IL-6 in a dose-dependent manner. The results of the present study add new dimension to levamisole's mode of action as inhibitor of CD138 and IL-6 and as an antiapoptotic agent. PMID- 29798961 TI - Prevalence of cytogenetic abnormalities in chronic lymphocytic leukemia in the southern part of Turkey. AB - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL. PMID- 29798963 TI - Prognostic significance of p16INK4a alteration in soft tissue sarcomas: A meta analysis. AB - PURPOSE: Numerous studies have investigated the role of p16INK4a alteration in patients with soft tissue sarcomas (STSs) yielding inconsistent and inconclusive results. Hence, we conducted a meta-analysis to precisely assess its prognostic value. MATERIALS AND METHODS: Electronic literature databases such as PubMed, EMBASE, Web of Science were searched, and five studies with a total of 536 patients were eligible for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) of overall survival (OS) was used to assess the prognostic role of p16INK4a alteration. RESULTS: Overall, the pooled HR for all five eligible studies evaluating decreased p16INK4a expression on OS was 1.47 (95% CI: 1.14-1.90); sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. There is no evidence of publication bias in the meta-analysis. CONCLUSIONS: In conclusion, this meta-analysis showed that decreased p16INK4a expression is associated with lower OS rate in patients with STS, and it is an effective biomarker of prognosis. PMID- 29798962 TI - Clinicopathological spectrum of teratomas: An 8-year retrospective study from a tertiary care institute. AB - BACKGROUND: Teratomas are tumors that contain tissues derived from three different germ cell layers and having a wider range of differentiation with different site and age at presentation. The aim of the present study was to know the frequency of teratomas in various sites and to analyze their clinicomorphological features. MATERIALS AND METHODS: The present study is a retrospective study conducted in tertiary care hospital of Central India. All the cases diagnosed as teratoma in the period of 8 years were included and studied with reference to age, sex, site, size, gross, and microscopic features. RESULTS: A total of 92 cases were retrieved. The most common teratoma was ovarian (78.26%) followed by intracranial/intraspinal and sacrococcygeal in frequency of 7.61% each. Out of 92 cases, 89 were mature and benign, 2 cases were immature teratoma each in ovary and in sacrococcyx, and 1 case of teratocarcinoma in testis. CONCLUSION: Teratomas have much diversity in their age at presentation, location, gross features, and in degree of differentiation. The prognosis and treatment also depends on the histological grading of teratomas. Thus, pathologists have an important role in establishing a reliable prognostic profile. PMID- 29798964 TI - Education differential in relation to tobacco use and its predictors across different regions of India. AB - BACKGROUND: Tobacco use and education of an individual are linked to each other. Educated people are more likely to practice healthy behaviors and are aware of the harms of tobacco use. This paper uses the Global Adult Tobacco Survey data (GATS-India) to study the education differential associated with tobacco use and its predictors across India. METHODOLOGY: Secondary data analysis was conducted for GATS conducted in 2009-2010 in India. Data for "illiterate" and "literate" study subjects were analyzed according to study subject's "tobacco consumption pattern," their "quitting behavior," "exposure to second hand smoke (SHS)" and "observing health warnings on tobacco products." RESULTS: Tobacco smokers and smokeless tobacco users were more likely to be illiterate (odds ratio [OR] for smoking tobacco = 1.2; for smokeless tobacco = 1.5) as compared to their counterparts. Significantly, more illiterate initiated smoking tobacco (OR = 1.1; 1.02-1.26) and smokeless tobacco habit (OR = 1.3; 1.21-1.44) before 17 years of age. Illiterate people were less likely to try quitting tobacco (smoking tobacco = OR = 0.8; 0.79-0.94; smokeless tobacco = OR = 0.7; 0.70-0.81) and also less likely to think of quitting tobacco in near future (smoking tobacco = OR = 0.6; 0.59-0.71; smokeless tobacco = OR = 0.6; 0.57-0.66). Illiterate people were more likely to be exposed to SHS at home (OR = 1.8; 1.7-1.9) and less likely to notice health warnings on cigarette packets (OR = 0.2; 0.26-0.28) and smokeless tobacco pouches (unadjusted OR = 0.5; 0.49-0.53). CONCLUSION: The results confirm that education differential exists for tobacco use and its determinants in India. It is recommended that all people of our country should have access to quality education. Policy makers should target uneducated people so as to reverse the tobacco epidemic. PMID- 29798965 TI - Expression and localization of aquaporins 3 and 7 in bull spermatozoa and their relevance to sperm motility after cryopreservation. AB - Artificial insemination with cryopreserved semen is a well-developed technique commonly used for controlled reproduction in cattle. However, despite current technical advances, cryopreservation continues to damage bull spermatozoa, resulting in a loss of approximately 30 to 50% of viable spermatozoa post thawing. To further improve the efficiency of cryopreservation of bull spermatozoa, understanding the molecular mechanisms underlying the cryobiological properties that affect cryoinjuries during cryopreservation process of bull spermatozoa is required. In this study, we examined the expression and localization of aquaporin (AQP) 3 and AQP7 in fresh, cooled, and frozen-thawed bull spermatozoa. Furthermore, we investigated the relevance of AQP3 and AQP7 to motility and to membrane integrity in frozen-thawed bull spermatozoa. Western blotting against AQP3 and AQP7 in bull spermatozoa revealed bands with molecular weights of approximately 42 kDa and 53 kDa, respectively. In immunocytochemistry analyses, immunostaining of AQP3 was clearly observed in the principal piece of the sperm tail. Two immunostaining patterns were observed for AQP7 -pattern 1: diffuse staining in head and entire tail, and pattern 2: diffuse staining in head and clear staining in mid-piece. Cooling and freeze-thawing did not affect the localization pattern of AQP7 and the relative abundances of AQP3 and AQP7 evaluated by Western blotting. Furthermore, we demonstrated that the relative abundances of AQP3 and AQP7 varied among ejaculates, and they were positively related to sperm motility, particularly sperm velocity, post freeze-thawing. Our findings suggest that AQP3 and AQP7 are possibly involved in the tolerance to freeze-thawing in bull spermatozoa, particularly in the sperm's tail. PMID- 29798966 TI - Effects of pre-maturational culture duration on developmental competence of bovine small-sized oocytes. AB - We investigated the effects of pre-maturational (pre-IVM) culture on the developmental competence of small-sized bovine oocytes (110 and < 115 um). Oocytes were cultured with 3-isobutyl-1-methylxanthine (IBMX) for 0, 5, or 10 h and subjected to in vitro maturation, fertilization, and culture. The cleavage rate (73%) of small-sized oocytes with 5 h pre-IVM was higher than those with 0 and 10 h pre-IVM (61 and 62%, respectively). The blastocyst rate (16%) of embryos derived from small-sized oocytes with 5 h pre-IVM was higher than those with 0 and 10 h pre-IVM (9 and 8%, respectively). In addition, small-sized oocytes with 5 h pre-IVM had a higher mean cell number in blastocysts (134.1 +/- 34.8) than those with 0 and 10 h pre-IVM (100.2 +/- 17.2 and 107.8 +/- 23.7, respectively). In conclusion, the pre-IVM of small-sized oocytes with IBMX for 5 h improved the developmental competence of bovine oocytes, as well as the quality of blastocysts. PMID- 29798967 TI - Tea polyphenols suppress growth and virulence-related factors of Haemophilus parasuis. AB - The bacterium Haemophilus parasuis (H. parasuis) is the primary cause of Glasser's disease. Currently, there are no effective vaccines that can confer protection against all H. parasuis serovars. Therefore, the present study aimed to investigate the effect of tea polyphenols on growth, expression of virulence related factors, and biofilm formation of H. parasuis, as well as to evaluate their protective effects against H. parasuis challenge. Our findings demonstrated that tea polyphenols can inhibit H. parasuis growth in a dose-dependent manner and attenuate the biofilm formation of H. parasuis. In addition, tea polyphenols exerted inhibitory effects on the expression of H. parasuis virulence-related factors. Moreover, tea polyphenols could confer protection against a lethal dose of H. parasuis and can reduce pathological tissue damage induced by H. parasuis. In summary, our findings demonstrated the promising use of tea polyphenols as a novel treatment for H. parasuis infection in pigs. PMID- 29798968 TI - Estimating the life expectancy of companion dogs in Japan using pet cemetery data. AB - The life expectancy provides valuable information about population health. The life expectancies were evaluated in 12,039 dogs which were buried or cremated during January 2012 to March 2015. The data of dogs were collected at the eight animal cemeteries in Tokyo. The overall life expectancy of dogs was 13.7 (95% confidence interval (CI): 13.7-13.8) years. The probability of death was high in the first year of life, lowest in the fourth year, and increased exponentially after four years of age like Gompertz curve in semilog graph. The life expectancy of companion dogs in Tokyo has increased 1.67 fold from 8.6 years to 13.7 years over the past three decades. Canine crossbreed life expectancy (15.1 years, 95% CI 14.9-15.3) was significantly greater than pure breed life expectancy (13.6 years, 95%CI 13.5-13.7, P-value <0.001). The life expectancy for male and for female dogs were 13.6 (95% CI: 13.5-13.7) and 13.5 (95% CI: 13.4-13.6) years, respectively, with no significant difference (P=0.097). In terms of the median age of death and life expectancy for major breeds, Shiba had the highest median age of death (15.7 years), life expectancy (15.5 years) and French Bulldog had the lowest median age of death (10.2 years), life expectancy (10.2 years). When considering life expectancy alone, these results suggest that the health of companion dogs in Japan has significantly improved over the past 30 years. PMID- 29798969 TI - Onset of Hemophagocytic Lymphohistiocytosis during Piperacillin-Tazobactam Therapy in Three Children with Acute Focal Bacterial Nephritis. AB - Hemophagoytic lymphohistiocytosis (HLH) is a rare life-threatening disorder caused by overactivation of the immune system, associated with infections, autoimmune disorders, and malignancies. The pathological hallmark of HLH is phagocytosis of blood cells and platelets by activated macrophages and histiocytes. In this report, we describe the onset of HLH in three children, aged 2, 5 and 7 years old, during the treatment of acute focal bacterial nephritis (AFBN) with an antibiotic, piperacillin-tazobactam (PIPC-TAZ). AFBN is acute localized bacterial infection of the kidney without abscess formation. PIPC-TAZ was chosen for the treatment of AFBN, because it not only has indications for complicated urinary tract infections, but also covers most of the causative bacteria of urinary tract infections, including beta-lactamase-producing Escherichia coli. The clinical courses of the three patients were similar, and they were treated with PIPC-TAZ and amikacin (AMK) for AFBN. Fever went down 2 to 5 days later, and AMK was discontinued by day 6. However, fever recurred on 13 to 15 days after introduction of PIPC-TAZ therapy, even though all of the patients had no signs of recurrence of AFBN. The clinical features and laboratory tests of two patients fulfilled the criteria of HLH, whereas the other patient had initiated therapy before fulfilling the criteria. Cessation of PIPC-TAZ combined with corticosteroid therapy improved clinical symptoms. HLH of our patients was probably induced by PIPC-TAZ, as judged by the timing of the onset of HLH and the positivity of the drug-lymphocyte stimulation test. In conclusion, prolonged antibiotic therapy with PIPC-TAZ could be a cause of HLH. PMID- 29798970 TI - Circular RNA Myosin Light Chain Kinase (MYLK) Promotes Prostate Cancer Progression through Modulating Mir-29a Expression. AB - BACKGROUND In developed countries, prostate cancer (PCa) is a frequently diagnosed cancer with the second highest fatality rate. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) stably expressed in cells and involved in a series of carcinomas. However, few research studies have reported on the role of circRNAs in PCa. MATERIAL AND METHODS We used qRT-PCR to detect the expression of circMYLK (circRNA ID: hsa_circ_0141940) and miR-29a in PCa tissues and cell lines. MTT, colony formation, and TUNEL assays were performed to analysis the cell viability of PCa cells. Transwell and wound scratch assays were performed to investigate the cell invasion and migration of PCa cells. RESULTS In the present study, we confirmed that circMYLK expression level was significantly higher in PCa samples and PCa cells than in normal tissues and normal prostatic cells. The upregulated circRNA-MYLK promoted PCa cells proliferation, invasion, and migration; however, si-circRNA-MYLK significantly accelerated the PCa cell apoptosis. We also observed that the aforementioned function of circRNA-MYLK on PCa cells was affected through targeting miR-29a. CONCLUSIONS We confirmed circRNA-MYLK was an oncogene in PCa and revealed a novel mechanism underlying circRNA-MYLK in PC progression. PMID- 29798971 TI - Prognostic Significance of Serum Interleukins and Soluble ST2 in Traditional Chinese Medicine (TCM) Syndrome-Differentiated Rheumatoid Arthritis. AB - BACKGROUND The aim of this study was to explore the possible correlations of serum interleukins and soluble ST2 (sST2) protein with clinical features and inflammatory cytokines in rheumatoid arthritis (RA) patients, as well as to assess ability of TCM (Traditional Chinese Medicine) syndromes to differentiate RA patients and evaluate prognosis. MATERIAL AND METHODS Thirty RA patients and 25 healthy individuals were enrolled. Syndrome activity was evaluated, and lab tests were performed. Serum levels of IL-10, IL-17, IL-33, and sST2 were assessed by ELISA. RESULTS Serum levels of sST2, IL-33, and pro-inflammation cytokine IL 17 were all up-regulated, while the immunosuppressive cytokine IL-10 was decreased in RA patients. Serum IL-33 level was positively associated with ESR, CRP, and RF, as well as with HAQ score, VAS score, and DAS28 scores (P<0.05). Serum sST2 level was correlated with the morning stiffness time and ESR, as well as scores of HAQ and DAS28 (P<0.05). In addition, IL-33 level was positively corelated with IL-17 (r=0.83, P<0.01) and the relative ratio of IL-10/IL-17 (r=0.904, P<0.01), and was negatively related with IL-10 (r=-0.632, P<0.01). TCM syndrome differentiation was conducted for RA patients, including the hot syndromes and cold syndromes groups. Hot syndromes RA patients had significantly more severe inflammation compared with cold syndromes patients. CONCLUSIONS IL-33 is a possible index for monitoring disease activity and inflammation condition in RA. IL-33 contributes to RA pathogenesis through unbalancing IL-10 and IL-17. In terms of TCM, hot syndromes RA presented more serious inflammation and more active disease activity, indicating a poorer prognosis. PMID- 29798973 TI - [Clinical presentations, diagnosis and treatment of cerebral vein and sinus thrombosis]. AB - The problem of thrombosis of cerebral veins and venous sinuses is insufficiently studied. The real incidence of cerebral venous thrombosis remains incompletely defined. The article presents results of clinical research on cerebral vein and sinus thrombosis, which served as a ground for an analysis of causes and development of the disease. In 20-35% of patients with cerebral venous thrombosis, this disease remains idiopathic after extensive investigation. Particular attention is given to risk factors, clinical presentations, early diagnosis, treatment, prognosis of cerebral vein and sinus thrombosis. PMID- 29798972 TI - Usefulness of Pancreas Donor Risk Index and Pre-Procurement Pancreas Allocation Suitability Score: Results of the Polish National Study. AB - BACKGROUND Pre-procurement pancreas suitability score (P-PASS) and pancreas donor risk (PDRI) index are scoring systems believed to predict suitability of pancreatic grafts. Most European countries and the United States apply PDRI, while Poltransplant keeps using P-PASS: more than 16 points raises a red flag for graft use. Recent data discourage use of PDRI to predict pancreas graft survival. The aim of the present study was to assess PDRI and P-PASS as predictors of transplanted pancreas survival in a Polish population. MATERIAL AND METHODS From February 1998 to September 2015, 407 pancreas transplantations were performed in Poland: 370 (90.9%) simultaneous pancreas-kidney transplantation and 37 (9.1%) pancreas transplantation alone or pancreas after kidney. The endpoint was death uncensored 12-month graft survival with satisfactory glycemic control without insulin. RESULTS Average P-PASS was 15.9+/-2.66 and PDRI was 0.96+/-0.37. Recipients who survived 12 months with good graft function had an average P-PASS score of 15.7 and PDRI of 0.95. Recipients with death-uncensored graft loss had a mean P-PASS of 16.4 and PDRI of 0.99. Univariate analysis revealed donor age, body mass index (BMI), and P-PASS to be significant risk factors for 1-year pancreas graft survival. CONCLUSIONS P-PASS, but not PDRI, is a reliable tool to predict pancreas graft survival in the Polish population. PMID- 29798974 TI - [Intimal rupture of the displastic middle cerebral artery wall complicated by thrombosis and fatal ischemic stroke]. AB - The authors present a clinical-morphological observation of the 47-year old man with a severe fatal ischemic stroke due to middle cerebral artery thrombosis which developed at the site of intimal rupture. The cause of intimal rupture was the arterial wall dysplastic changes. There were no signs of atherosclerosis and hypercoagulation. As the intima rupture did not lead to blood input into arterial wall, but was accompanied by superimposed thrombosis, we suggested to denote such cases as incomplete dissection. PMID- 29798975 TI - [Ischemic stroke in the patients with comorbid pathology]. AB - AIM: To study an effect of comorbidity on the course and outcome of ischemic stroke (IS). MATERIAL AND METHODS: Results of a unicenter, retrospective, cohort study of 190 patients with ischemic stroke (IS) were analyzed. Severity of stroke, dependence in the daily activities, comorbidity were assessed using NIHSS, the Rankin scale,CCI, CIRS. RESULTS AND CONCLUSION: The correlation of IS severity and outcome with the severity of comorbid pathology assessed by CCI and CIRS was identified. Severity of comorbid pathology increased with the age of patients. Comorbidity (CCI) and stroke severity (NIHSS) were predictors of IS outcome (the Rankin scale) (R=0.72210324; R2=0.52143308; p=0.0026). The effect of comorbidity on survivability of stroke was shown. The results can be useful for the management of the patient with acute IS in a specialized inpatient setting. PMID- 29798976 TI - [Clinical/epidemiological characteristics of ischemic stroke in Dagestan]. AB - OBJETIVE: To analyze risk factors and course of acute ischemic stroke (IS) based on hospital register data. MATERIAL AND METHODS: Ninety-seven patients (38 women and 59 men, mean age 65.4+/-12.8 and 61.2+/-18.8 years, respectively) with acute IS admitted in 2016 to the Clinical hospital of Makhachkala were examined. Medical history and severity of neurological deficit (the British Medical Council Scale, The Glasgow Coma Scale, MMSE) were assessed. RESULTS: The severity of neurological deficit was comparable in men and women though cognitive impairment was more frequent in women (p<0.05). At admission, symptoms of inflammation and hyper coagulation were more frequently identified in women (p<0.05). The high prevalence of chronic cerebral ischemia preceding IS, insufficient efficacy of preventive treatment and late hospitalization were noted. CONCLUSION: The results should be confirmed in a large-scale long-term study. They can be used to improve quality of medical care of patients with IS. PMID- 29798977 TI - [The Russian version of Coma Recovery Scale-revised - a standardized method for assessment of patients with disorders of consciousness]. AB - The authors officially present for the first time the Russian version of Coma Recovery Scale-Revised (CRS-R). Today CRS-R is the only validated scale in Russian for assessment of patients with chronic disorders of consciousness (DOC). The study showed high consistency for different researchers, high sensitivity in the evaluation of patients over time as well as high concurrent validity. This article contains the text of the scale and recommendations how to use CRS-R and interpret the data. Presented version of the CRS-R is recommended for use in DOC patients. Russian version of the CRS-R is a standardized, comprehensive and systematic approach to the examination and assessment of patients with chronic DOS. It ensures the standard approach to examination and assessment that warrants the accuracy and homogeneity of the obtained results. PMID- 29798978 TI - [The relationship of pathological ankle-brachial index and cognitive decline in patients after ischemic stroke]. AB - AIM: To identify associations between cognitive impairment and values of ankle brachial index (ABI) in patients after ischemic stroke at discharge from the hospital and over one-year follow-up. MATERIAL AND METHODS: The study included 375 patients with normal (n=192) and elevated (n=153) ABI who underwent ischemic stroke (IS). Neurological examination was performed using NIHSS, the Rankin scale, Barthel index, Rivermead Mobility Index at discharge from the hospital and over one-year follow-up. RESULTS AND CONCLUSION: Patients with elevated ABI had marked cognitive impairment and more severe neurological deficit compared to patients with normal ABI. Evaluation of ABI can help in predicting the development of post-stroke cognitive impairment in patients with IS. PMID- 29798979 TI - [The state of microcirculation and platelet hemostasis in patients with ischemic stroke after systemic thrombolytic therapy]. AB - AIM: The state of microcirculation and platelet hemostasis in patients with ischemic stroke after systemic thrombolytic therapy. MATERIAL AND METHODS: Forty two patients after systemic thrombolytic therapy (TLT) (mean age 64.26 [60.58; 68.06]) and 47 patients without TLT (54.52 [47.48; 60.83]) were studied. The study of platelet hemostasis was conducted with the determination of platelet aggregation (AT) on adrenaline, ADP, ristomycin, spontaneous aggregation on days 1, 7 and 14. Studies of the state of microcirculation of cerebral vessels were carried out using the laser Doppler flowmetry (LDF). RESULTS AND CONCLUSION: Characteristics of changes in induced AT and parameters of the microcirculation system in patients after systemic TLT at 1, 7 and 14 days in comparison with the indices of patients without TLT were revealed that allowed to expand the understanding of pathological mechanisms of the microcirculatory bed, their connection with violations of central hemodynamics and to obtain additional markers of disease course and prognosis. PMID- 29798980 TI - [A role of microRNA in the pathogenesis of ischemic stroke]. AB - Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Among all the causes of IS, cardioembolic stroke (CEI) accounts for up to 40%. Based on the literature data, modern ideas about the role and location of cardiac diseases in the pathogenesis of CEI are presented. The leading cause of CEE is non-rheumatic atrial fibrillation. Numerous attempts to study and prove the genetic nature of the development of IS led to the discovery of new markers - micribonucleic acids (microRNAs), the regulators of gene expression, that inhibit mRNA translation and play a key role in the pathogenesis of IS. This review summarizes the current knowledge of microRNAs, their ability to simultaneously regulate several target genes, and their significance as potential diagnostic and prognostic biomarkers in IS. PMID- 29798981 TI - [MicroRNA in ischemic stroke]. AB - Today, stroke is the third most common pathology after cardiovascular disease and cancer, as well as the leading cause of disability in the world. Although some progress has been made in the field of primary and secondary stroke prevention over the past few decades, a deeper knowledge of the pathophysiology of the disease is needed to significantly improve diagnosis and therapy. MicroRNA (miRNA) is an important, recently identified class of posttranscriptional regulators of gene expression. MiRNA can be used as a tool for therapeutic interventions. This review considers a role of miRNAs in the regulation of experimental stroke and in the development of carotid artery stroke. A potential role of miRNAs as promising biomarkers of stroke is discussed. PMID- 29798982 TI - [The efficacy of systemic thrombolysis in patients with cardioembolic stroke]. AB - AIM: To compare the efficacy and safety of systemic thrombolytic therapy (STLT) in patients with cardioembolic stroke (CE) versus other pathogenic subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 147 patients, 62 women and 85 men (mean age - 62.9+/-0.8 years) including 37 patients (25.2%) with CE subtype of IS (group 1) and 110 patients with other pathogenetic subtypes of IS (group 2). NIHSS and Rankin scale were used to assess patient's neurological status. RESULTS: One hundred and twenty-six patients were discharged, 21 (14.3%) died. In 11 patients, the cause of death was the development of symptomatic hemorrhagic transformation (SHT). There were no significant differences in the lethality between groups 1 and 2. Tolerability to STLT in these groups did not differ as well. As a result of treatment, the condition of patients surviving to the end of the hospital stay improved, which was reflected in a significant decrease in the NIHSS scores, despite the higher NIHSS scores in group 1. CONCLUSION: The results confirm the efficacy of STLT in patients with CE IS and indicate the increase in the frequency of favorable functional recovery in these patients. PMID- 29798983 TI - [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. AB - AIM: To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS). MATERIAL AND METHODS: One hundred and ten patients after IS (43 men, 67 women, mean age 58.0+/-9.7, Me 63 years) were examined. All patients were divided into early (89+/-9 days) and late (214+/-22 days) rehabilitation groups. Each group was subdivided into semax+ and semax- subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups. RESULTS: Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. CONCLUSION: Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance. PMID- 29798984 TI - [Assessment of the efficacy of mexidol in the combination with hyperbaric oxygen in acute ischemic stroke]. AB - To study the efficacy of mexidol in the combination with hyperbaric oxygenation (HBO) in comparison with the standard HBO sessions in patients with acute ischemic stroke. One hundred and twelve patients were examined. In the main group, 48 patients underwent HBO and received treatment with mexidol. The control group consisted of 64 people who underwent the standard HBO sessions only. The use of combination therapy (HBO+mexidol) leads to the significantly more rapid normalization of acute phase indices which are correlated with neurological deficit reduction. PMID- 29798985 TI - [Geometric and morphological features of the aortic root in norm and aortic regurgitation]. AB - AIM: To assess linear and geometric parameters of the aortic valve and to determine the changes which are associated with impaired leaflets coaptation and aortic root enlargement. MATERIAL AND METHODS: Surgical anatomy of the aortic root and its spatial relationships with surrounding heart structures were studied with plastination by using of combined silicon technologies. 123 specimens of the aortic root with preserved original geometry were created with silicone plastination technique and perfusion embalming. Analysis included 15 heart specimens with the signs of aortic root dilatation and 108 specimens without evidence of dilatation. Multiple logistic regression was used for statistical analysis. RESULTS: Anatomical and clinical analysis showed that deviation angle of the intercusp triangle is the factor contributing impaired aortic root geometry and aortic regurgitation (OR 1.3, 95% CI 1.114-1.350, p<0.0001). CONCLUSION: 1) Increased deviation angle of intercusp triangles is associated with impaired coaptation of aortic valve leaflets. 2) Restoration of intercusp triangle deviation angle within 1.7+/-1.2 degrees degrees is geometrically necessary to achieve normal function of the aortic valve. PMID- 29798986 TI - [Five-year outcomes of aorto-femoral vascular reconstructions in patients with multifocal atherosclerosis]. AB - AIM: To analyze long-term results of surgical treatment of atherosclerotic occlusive-stenotic lesion of aorto-femoral segment within the single-center prospective register. MATERIAL AND METHODS: The study included 275 patients who underwent aorto-femoral reconstructive interventions for the period 2011-2014. Inclusion criterion was indications for aorto-femoral surgery due to severe atherosclerotic lesions of the infrarenal aorta and/or ilio-femoral arteries. Mean follow-up was 54+/-11.6 months. RESULTS: Prognostic significance of various clinical-instrumental, anatomical-angiographic and perioperative variables has been comprehensively analyzed. Five-year outcomes and cardiovascular morbidity were assessed in consecutive patients after reconstructive procedures on the aorto-femoral segment. Multidisciplinary approach to determine optimal revascularization strategy and certain tactical and technical algorithms are necessary to improve the outcomes in these severe patients. PMID- 29798987 TI - [DIC-syndrome-related mortality in acute necrotic pancreatitis]. AB - AIM: To improve the results of acute necrotic pancreatitis management via an analysis of changes in the main causes of mortality in patients with this disease over the last decade. MATERIAL AND METHODS: We have analyzed medical records of patients with acute necrotic pancreatitis followed by lethal outcome for the period 2015-2016. In all cases autopsy was performed in order to determine morbidity and mortality. Complications of pancreatic necrosis significant for tanatogenesis, treatment and prevention strategy were compared with those for 2005-2006. RESULTS: It was shown that not only significantly decreased mortality in acute necrotic pancreatitis but also important changes in its structure occurred for the last ten years. At present time DIC-syndrome and its organ complications are the most significant causes of death. CONCLUSION: Prevention of DIC-syndrome and its complications is necessary to improve the outcomes. Endothelial protectors' administration in early period, timely diagnosis and adequate treatment of DIC-syndrome are advisable. PMID- 29798988 TI - [Diagnosis and treatment of gallstone intestinal obstruction]. AB - AIM: To analyze informative value of radiological examination in diagnosis of acute gallstone intestinal obstruction. MATERIAL AND METHODS: Diagnosis and treatment of 7 patients with acute gallstone intestinal obstruction have been analyzed. Diagnostic protocol included radiography of abdominal cavity, sonography and computed tomography. RESULTS: Computed tomography within the first hours after hospitalization is highly informative to diagnose gallstone intestinal obstruction if other methods are ineffective. CONCLUSION: Inclusion of computed tomography into survey algorithm optimizes diagnostic process, clarifies the cause of acute intestinal obstruction and promptly determines the indications for video-assisted surgery. PMID- 29798989 TI - [The features of opisthorchiasis papillitis diagnosis]. AB - AIM: To develop an optimal diagnostic algorithm in order to the most reliable decrease of inflammatory changes severity in large duodenal papilla in patients with chronic opisthorchiasis. MATERIAL AND METHODS: Medical reports of 384 patients with opisthorchiasis-induced cholangitis have been analyzed. Diagnostic methods were abdominal ultrasound, endoscopic ultrasound of terminal common bile duct, CT scans, MRI of abdominal organs including magnetic resonance cholangiopancreatography and esophagogastroduodenoscopy with biopsy of the papilla, ERCP and PTHC. Comprehensive general and individual analysis of each of them has determined their advantages and disadvantages. CONCLUSION: Examination should by comprehensive to evaluate visual appearance of large duodenal papilla, lumen dimensions, state of its walls with histological research. Imaging tests are favorable to determine the diagnosis of papillitis due to possible assessment of lumen dimensions and state of the walls. While making a choice the priority should be given to endoscopic ultrasound examination. It allows visual inspection, assessment of the lumen, the walls of papilla and provides biopsy of deep structures. PMID- 29798990 TI - [Intussusception followed by intestinal obstruction in adults]. AB - AIM: To evaluate the effectiveness of complex preoperative diagnostics and medication of intussusception followed by intestinal obstruction in adults with the choice of surgical repair and analysis of the outcomes depending on the causes of intussusception. MATERIAL AND METHODS: 15 intussusception patients aged 19 - 86 years were enrolled. Mean age was 52.7 years. Patients were hospitalized within 12 hours - 1-2 weeks after onset of the disease. Diagnosis was established on the basis of complaints, anamnesis, objective and additional survey. All patients underwent abdominal X-ray and ultrasound. Intestinal obstruction at admission was diagnosed in all patients, and only 1 (6.7%) of them had intussusception. RESULTS: Medication and additional survey contributed to detection of intussusception followed by intestinal obstruction in 13 (86.7%) out of 15 patients prior to surgery. All patients underwent urgent or delayed surgery. Small intestine resection was performed in 9 patients, 2 patients underwent resection of small intestine with submucosal tumor (1) and Meckel's diverticulum (1) after intussusception repair. Right-sided hemicolectomy was performed in 3 patients, sigmoid colon resection with lymph nodes dissection - in 1 patient. The cause of intussusception followed by intestinal obstruction were epithelial and stromal tumors (9), less often metastasis of melanoma (2), Meckel's diverticulum (1) and functional bowel disorders (1). Postoperative complications arose in high risk patients hospitalized after 24 hours from onset of the disease and present concomitant diseases and malignancies. 1 (6,7%) patient died. PMID- 29798991 TI - [Prospects of combined anterior prosthetic hernia repair in treatment of large and giant ventral hernias]. AB - AIM: To evaluate clinical efficacy of combined anterior prosthetic hernia repair in treatment of large and giant ventral hernias. MATERIAL AND METHODS: Patients with large and giant hernias have been analyzed. In the main group (n=675) combined methods of hernia gates repair were applied, in control group (n=257) - stretching repair including prosthesis deployment. Surgeons (n=22) were interviewed for learning curve, safety, limitations and reliability of combined methods. RESULTS: Combined method of hernia repair in patients with large and giant hernias reduces overall postoperative morbidity (p<0.001), wound complications (p<0.05) and incidence of recurrent hernia (p<0.001). Questionnaire data showed the possibility of learning for the method by the most of surgeons to treat these patients. As a result, some practical recommendations are presented for successful procedures and satisfactory results of treatment. PMID- 29798992 TI - [Compression anastomoses with nikelid-titanium rings in peritonitis]. AB - AIM: To introduce into clinical practice compression anastomosis with nikelid titanium rings (NTR) with shape memory in advanced peritonitis patients who need for intestinal resections. MATERIAL AND METHODS: Seventy-six procedures of interintestinal anastomoses with NTR (Gunter-Ziganshin implant) have been analyzed for the period 2011-2017. Interventions were carried out for widespread peritonitis. In all cases a unified technique of anastomosis was used by applying an implant in the form of a 'clerical clip'. There were following procedures: gastroenterostomy resection for its failure - 5; small intestine resection followed by interntestinal anastomosis - 36; ileotransverso- or colocolostomy - 35. RESULTS: Mean time of enteroenterostomy was 2.6+/-0.98 min. If elective re laparomy was supposed, laparostomy was formed followed by sanation within 48 hours. In 55% of patients 3-5-fold elective sanations were performed. Adequacy of compression anastomoses was assessed clinically according to the nature of drainage output and visually during redo surgery. There were 11 (14.5%) deaths: 9 (12%) patients had APACHE-II score over 20. Macro- and microscopic analysis of intestinal specimens and interintestinal anastomoses with nikelid-titanium rings showed complete impermeability and no visual defects. Microscopically neutrophilic leukocyte infiltration and increased number of fibroblasts were observed as the evidence of regenerative processes activation. Implant rejection time was 7.8+/-1.4 days. CONCLUSION: The use of compression anastomoses in case of advanced peritonitis reduces the risk of anastomosis failure to 3% and decreases time of surgery that reduces intraoperative aggression and improves outcomes in patients with prognostically unfavorable outcomes. PMID- 29798993 TI - [Diagnostic value of molecular biomarkers of infection in screening by Sepsis-3 criteria]. AB - AIM: To compare diagnostic value of molecular biomarkers of sepsis in patients with surgical infection in screening via Sepsis-2 (Surviving Sepsis Campaign 2012, SSC 2012) and Sepsis-3 (The Third International Consensus Definitions for Sepsis and Septic Shock) criteria. MATERIAL AND METHODS: Septic patients according to Sepsis-2 and Sepsis-3 criteria were identified from general population with surgical infection. Logistic regression models quality was the criterion for assessment of diagnostic value of molecular biomarkers. Risk factors importance was estimated via odds ratios (OR) calculation. RESULTS: Sepsis-3 ROC-AUC for procalcitonin increased up to 0.933, cut-off value 2.35 ng/ml (Sepsis-2 AUC 0.768 (p=0.004), cut-off 1.72 ng/ml). Sepsis-3 ROC-AUC for presepsin increased up to 0.932, cut-off value - 772 pg/ml (Sepsis-2 AUC 0.865, cut-off 567 pg/ml). The highest risk of sepsis was observed in systemic response to inflammation combined with organ dysfunction (OR 69.667, S 0.636; 95% CI 20.03 242.4) (Sepsis-2 - OR 9.25, S 0.548; 95% CI 3.2-27.1, p<0.001). Increased levels of both biomarkers significantly increased the risk of sepsis (OR 22.5, S 0.794; 95% CI 4.74-106.6 and OR 20.97, S 0.58; 95% CI 6.705-65.6, respectively). CONCLUSION: Organ dysfunction assessment by Sepsis-3 criteria improves diagnostic possibilities in patients with suspected sepsis. Maximum predictive value is observed for systemic inflammation response combined with organ dysfunction. In these patients procalcitonin and presepsin are characterized by equivalent high diagnostic potential for evidence of infectious nature of the disease. Increased level of these markers can serve as a basis for antimicrobial therapy administration. PMID- 29798994 TI - [The role of CO2-laser in scarring management]. AB - AIM: To assess the role of CO2-laser in treatment of various scars and to determine the indications for its application. PATIENTS AND METHODS: It has been carried out a prospective analysis of treatment of 218 patients with scars of different duration, locations and anatomic areas with the use of CO2-laser for the period 2011-2017. POSAS scale and sonography were used for analysis. RESULTS: 1. Laser therapy is not effective for scarring-related functional defects (contractures, ectropion, microstomia), when surgery is indicated. 2. The outcomes of treatment (both surgical and laser) depend on the time of existence of the scars rather their cause and anatomical region. 3. Laser therapy is not effective enough for formed scars existing over 12 months. 4. Laser therapy is effective for immature scars, especially indicated for cicatricial deformation when the aesthetics cannot be repaired with traditional surgery. CONCLUSION: Application of CO2-laser in scars treatment with regard to its real efficiency determines the effectiveness of therapy. PMID- 29798995 TI - [Surgical approaches in urgent and elective surgery of the neck]. AB - AIM: To define surgical approaches which provide surgical adequacy, preservation of function and aesthetic results. MATERIAL AND METHODS: Analysis included 191 emergency interventions for various neck injuries and more than 35.000 elective operations for thyroid diseases. RESULTS: The study showed that collar-like incisions have the best aesthetic effect on the neck; an approach along anterior margin of the sternocleidomastoid muscle is advisable for emergency assessment of cervical organs; W.F. MacFee access is optimal for lateral cervical lymphadenectomy in asthenic patients while serpentine incision - in hypersthenic ones. PMID- 29798996 TI - [Surgical treatment of pectus carinatum in children]. AB - AIM: To improve the results of surgical treatment of pectus carinatum. MATERIAL AND METHODS: The work included 47 pectus carinatum patients aged 3-15 years for the period from 2000 to 2015. All patients were divided into 2 groups depending on surgical approach: control group - 23 (48.94%) children who underwent thoracoplasty by M.M. Ravitsh procedure with the use of device for pectus carinatum repair of our design; main group - 24 (51.06%) patients where our method of thoracoplasty based on changes of deformed ribs biomechanics was used. RESULTS: In control group good results were obtained in 15 (65.3%) patients, satisfactory - in 5 (21.7%) patients, recurrent deformation with all consequences was observed in 3 (13%) cases. Long-term results of surgical treatment by original method were followed-up in all 24 patients and good outcomes were obtained in 100% of children. CONCLUSION: 1) Intraoperative 'spring' - effect is a provoking risk factor of recurrent chest deformation. 2) The new surgical method based on breaking the ribs bodies in 'green branch' fashion provides good results and does not require external devices to hold sternal-rib complex in corrected position. PMID- 29798998 TI - [Forced osteoarthritis therapy: expanding the scope of the possible]. AB - The article deals the modern concepts of the mechanism of pain in osteoarthritis. It was established that synovial inflammation and immune disorders play an important role in the pathogenesis of pain in osteoarthritis. Hyperproduction of pro-inflammatory cytokines supports inflammation and degradation of cartilaginous tissue in osteoarthritis. The mechanisms of pathogenetic action of chondroitin sulfate are disclosed, and the evidence base of its preclinical and clinical studies in the treatment of osteoarthritis is presented. The data of clinical application of the Mucosat - pharmaceutical substance chondroitin sulfate in the form of a ready-made dosage form for intramuscular injection are presented. The practical advantages of including SYSADOA in complex therapy of osteoarthritis are discussed. PMID- 29798997 TI - [Effectiveness of biological prosthesis for femoro-femoral bypass in high risk patients]. AB - AIM: To compare synthetic and biological prostheses for femoral bypass surgery. MATERIAL AND METHODS: There were 40 patients with critical ischemia of lower extremities due to atherosclerotic lesion of aorto-iliac segment and severe comorbidities. They were divided into 2 groups by 20 patients. C-shaped femoro femoral bypass with synthetic polytetrafluoroethylene and lavsan prostheses was performed in the first group and S-shaped bypass procedure with biological prosthesis from the internal thoracic arteries of the bull - in the second group. RESULTS: Biological prosthesis is associated with reduced early postoperative morbidity by 10%, late graft thrombosis incidence by 20% and increased physical and psychological health by 7.1%. CONCLUSION: S-shaped femoro-femoral bypass with a biological prosthesis from the internal thoracic arteries of the bull is pathogenetically substantiated and effective. PMID- 29798999 TI - [Surgical treatment of the diaphragmatic hernia and the possibility of new endoscopic procedures]. PMID- 29799000 TI - [Transaortic mitral valve replacement in patient with combined heart valve disease]. PMID- 29799001 TI - [Radical surgery for locally advanced recurrent sigmoid colon cancer]. PMID- 29799002 TI - [Primary esophageal melanoma]. PMID- 29799003 TI - [Partial atrioventricular septal defect repair in 72 years old patient]. PMID- 29799005 TI - ['No-touch' technique for great saphenous vein harvesting]. PMID- 29799004 TI - [Pancreaticopleural fistula is a possible cause of acute respiratory failure]. PMID- 29799006 TI - Update on glycerol-3-phosphate acyltransferases: the roles in the development of insulin resistance. AB - Glycerol-3-phosphate acyltransferase (GPAT) is the rate-limiting enzyme in the de novo pathway of glycerolipid synthesis. It catalyzes the conversion of glycerol-3 phosphate and long-chain acyl-CoA to lysophosphatidic acid. In mammals, four isoforms of GPATs have been identified based on subcellular localization, substrate preferences, and NEM sensitivity, and they have been classified into two groups, one including GPAT1 and GPAT2, which are localized in the mitochondrial outer membrane, and the other including GPAT3 and GPAT4, which are localized in the endoplasmic reticulum membrane. GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. Through gain-of-function and loss-of-function experiments, it has been confirmed that GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. In line with this, the role of GPATs in metabolism was supported by studies using a GPAT inhibitor, FSG67. Additionally, the functional characteristics of GPATs and the relation between three isoforms (GPAT1, 3, and 4) and insulin resistance has been described in this review. PMID- 29799010 TI - Altered ammonia metabolism in ccRCC. PMID- 29799011 TI - IL-1beta switches on kidney fibrosis. PMID- 29799007 TI - Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. AB - Myotube formation by fusion of myoblasts and subsequent elongation of the syncytia is essential for skeletal muscle formation. However, molecules that regulate myotube formation remain elusive. Here we identify PIEZO1, a mechanosensitive Ca2+ channel, as a key regulator of myotube formation. During myotube formation, phosphatidylserine, a phospholipid that resides in the inner leaflet of the plasma membrane, is transiently exposed to cell surface and promotes myoblast fusion. We show that cell surface phosphatidylserine inhibits PIEZO1 and that the inward translocation of phosphatidylserine, which is driven by the phospholipid flippase complex of ATP11A and CDC50A, is required for PIEZO1 activation. PIEZO1-mediated Ca2+ influx promotes RhoA/ROCK-mediated actomyosin assemblies at the lateral cortex of myotubes, thus preventing uncontrolled fusion of myotubes and leading to polarized elongation during myotube formation. These results suggest that cell surface flip-flop of phosphatidylserine acts as a molecular switch for PIEZO1 activation that governs proper morphogenesis during myotube formation. PMID- 29799008 TI - Author Correction: Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms. AB - The originally published version of this article contained an error in the spelling of the author Pankaj Tailor, which was incorrectly given as Pankaj Taylor. This has now been corrected in both the PDF and HTML versions of the article. PMID- 29799012 TI - T cell balancing act in TB. PMID- 29799009 TI - Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients. AB - Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. Here, we present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. We reveal that Chinese patients are specially characterized by not only highly clustered EGFR mutations but a mutational signature (MS3, 33.7%), that is associated with inflammatory tumor-infiltrating B lymphocytes (P = 0.001). The EGFR mutation rate is significantly increased with the proportion of the MS3 signature (P = 9.37 * 10-5). TCGA data confirm that the infiltrating B lymphocyte abundance is significantly higher in the EGFR-mutated patients (P = 0.007). Additionally, MS3 high patients carry a higher contribution of distant chromosomal rearrangements >1 Mb (P = 1.35 * 10-7), some of which result in fusions involving genes with important functions (i.e., ALK and RET). Thus, inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers. PMID- 29799013 TI - Publisher Correction: The CaMKII holoenzyme structure in activation-competent conformations. AB - This corrects the article DOI: 10.1038/ncomms15742. PMID- 29799014 TI - Corrigendum: A Stronger Multi-observable Uncertainty Relation. AB - This corrects the article DOI: 10.1038/srep44764. PMID- 29799017 TI - Publisher Correction: Examining a Thermodynamic Order Parameter of Protein Folding. AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. PMID- 29799016 TI - Reproductive parasitism by worker honey bees suppressed by queens through regulation of worker mandibular secretions. AB - Social cohesion in social insect colonies can be achieved through the use of chemical signals whose production is caste-specific and regulated by social contexts. In honey bees, queen mandibular gland pheromones (QMP) maintain reproductive dominance by inhibiting ovary activation and production of queen like mandibular gland signals in workers. We investigated whether honey bee queens can control reproductively active workers of the intraspecific social parasite Apis mellifera capensis, parasitising A. m. scutellata host colonies. Our results show that the queen's QMP suppresses ovarian activation and inhibits the production of QMP pheromone signals by the parasitic workers, achieved through differential expression of enzymes involved in the biosynthesis of these pheromones at two points in the biosynthetic pathway. This is the first report showing that honey bee queens can regulate reproduction in intraspecific social parasites and deepens our understanding of the molecular mechanisms involved in the regulation of worker reproduction in social insects. PMID- 29799018 TI - New insights towards strikingly improved room temperature ethanol sensing properties of p-type Ce-doped SnO2 sensors. AB - In this article, room temperature ethanol sensing behavior of p-type Ce doped SnO2 nanostructures are investigated successfully. Interestingly, it is examined that the abnormal n to p-type transition behavior is caused by Ce doping in SnO2 lattice. In p-type Ce doped SnO2, Ce ion substituting the Sn is in favor of generating excess holes as oxygen vacancies, which is associated with the improved sensing performance. Although, p-type SnO2 is one of the important materials for practical applications, it is less studied as compared to n-type SnO2. Pure and Ce doped SnO2 nanostructures were successfully synthesized by chemical co-precipitation method. The structure, surface morphology, unpaired electrons (such as free radicals), and chemical composition of obtained nanoparticles were studied by various kinds of characterization techniques. The 9% Ce doped SnO2 sensors exhibit maximum sensor response of ~382 for 400 ppm of ethanol exposure with fast response time of ~5 to 25 sec respectively. Moreover, it is quite interesting that such enhancement of ethanol sensing is unveiled at room temperature, which plays a key role in the quest for better ethanol sensors. These remarkably improved sensing results are attributed to uniformly distributed nanoparticles, lattice strain, complex defect chemistry and presence of large number of unpaired electrons on the surface. PMID- 29799015 TI - Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity. AB - DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid ("surrogate challenge"). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-gamma production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T cells, targeted epitopes at aa 199-220 and aa 528-543. Drug-resistance mutations disrupted the epitope at aa 205-220, while the CTL epitope at aa 202-210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape. PMID- 29799019 TI - A novel technique for the measurement of eyelid contour to compare outcomes following Muller's muscle-conjunctival resection and external levator resection surgery. AB - BACKGROUND: Both external levator resection (ELR) and Muller's muscle conjunctival resection (MMCR) are procedures well known to improve marginal reflex distance (MRD1) in patients with ptosis. This study aims to understand differential post-operative changes in eyelid contour for MMCR and ELR surgery. METHODS: In this cross-sectional cohort study, patients affected by involutional ptosis were randomized into two groups: those who underwent ELR or MMCR surgery. Pre-operative and late post-operative photographs were obtained. Digital analysis of the lid contour was performed by measuring the vertical distance from a line intersecting the center of the pupil to the eyelid margin at 10 positions at 2 mm intervals. Mean distance at each position was compared pre- and post-operatively between the groups. RESULTS: The final sample included 60 eyes from 39 patients, 30 eyes per group. At each time point there was significant variation in height across the eyelid (p < 0.05). A significant (p < 0.05) group difference in vertical height was noted only at the 2 and 4 mm temporal positions in the post operative analysis, with the ELR group being slightly higher. There were no significant differences in MRD1, pre- or post-operatively, between the ELR and MMCR groups. CONCLUSIONS: Both ELR and MMCR are effective at elevating the eyelid in multiple positions across the length of the eyelid. Although they do not produce significantly different MRD1 results, ELR was associated with a greater eyelid height at the 2 and 4 mm temporal positions. PMID- 29799021 TI - Anticancer efficacy of noble metal nanoparticles relies on reprogramming tumor associated macrophages through redox pathways and pro-inflammatory cytokine cascades. PMID- 29799022 TI - Lactase persistence may explain the paradoxical findings of high vitamin D concentrations in Europeans living in areas of low UV-B irradiation. AB - BACKGROUND/OBJECTIVES: Vitamin D has a critical role in skeletal health and maintaining serum calcium levels. Calcium is needed for a variety of cellular and metabolic processes in the body. Large amounts of vitamin D can be produced in the skin when exposed to UV-B radiation. It is therefore a paradox that in Europe, Caucasians living in higher latitude countries, such as Scandinavia and Iceland, have higher serum vitamin D compared with those living in lower latitude. In a recent study of adult-type lactase persistence (LP), it was shown that Caucasian of European descent, who carried the C-13910T LP allele, had higher levels of total serum 25-hydroxyvitamin D compared with those who were lactase non-persistent. This was attributed to higher consumption of dairy. We postulated that the distribution of the LP C-13910T allele in Caucasian populations may explain the vitamin D concentration pattern seen in Europe. SUBJECTS/METHODS: Baseline mean total serum 25 hydroxyvitamin D concentration from a clinical trial of post-menopausal women with osteoporosis was correlated to published LP frequencies in European populations. RESULTS: In multiple regression analysis, mean total serum 25 hydroxyvitamin D concentrations in both winter and summer were in turn correlated to LP phenotype frequency (winter: r2 = 0.51, p < 0.05; summer: r2 = 0.4, p < 0.05). CONCLUSIONS: High frequency of LP in northern Europe may explain high mean total serum 25 hydroxyvitamin D concentrations despite low UV-B radiation exposure. PMID- 29799020 TI - Adjusted Troponin I for Improved Evaluation of Patients with Chest Pain. AB - The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with rage = 0.436/0.518 and with reGFR = -0.142/-0.207. For adjustment, these variables served as covariates in a linear regression model with cTnI as dependent variable. This adjustment model was then applied to a real world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients. PMID- 29799023 TI - Obesity and the future of food policies that promote healthy diets. AB - Currently, an unhealthy diet is the largest modifiable factor in ill health and death globally. One of the important contributors to unhealthy diets is the pervasiveness of unhealthy food and drink in our daily food environments. Although efforts to build nutrition skills and education across communities are critical, they will be insufficient without substantial changes to the food environments themselves. Here, I discuss how we can improve our food environments by implementing a comprehensive, multilevel and multisetting approach. This approach needs to encompass the various policy contexts for improving population nutrition, from policy set by national governments to that introduced by local community organizations and food retailers. Clinicians can help implement and set healthy food policies across all our health-care settings, even in the absence of government action. To support a comprehensive suite of effective policies, we need to systematically develop and disseminate the evidence for the feasibility, effectiveness and sustainability of workable policies and to understand their role in the development of a healthier food system. PMID- 29799024 TI - Maternal predator odour exposure programs metabolic responses in adult offspring. AB - A cardinal feature of the reaction to stress is the promotion of energy mobilization, enabling appropriate behavioural responses. Predator odours are naturalistic and ecologically relevant stressors present over evolutionary timescales. In this study, we asked whether maternal predator odour exposure could program long-term energy mobilization in C57BL/6 mice offspring. To test this hypothesis, we measured rates of oxygen consumption in prenatally predator odour exposed mice in adulthood while controlling for levels of locomotor activity at baseline and under stress. Circulating thyroid hormone levels and the transcript abundance of key regulators of the hypothalamic-pituitary-thyroid axis within the periventricular nucleus (PVN) of the hypothalamus and in the liver, including carriers and receptors and thyrotropin-releasing hormone, were measured as endocrine mediators facilitating energy availability. Prenatally predator odour exposed mice of both sexes mobilized more energy during lower energy demand periods of the day and under stressful conditions. Further, prenatally predator odour exposed mice displayed modifications of their hypothalamic-pituitary thyroid axis through increased circulating thyroxine and thyroid hormone receptor alpha within the PVN and decreased transthyretin in the liver. Overall, these results suggest that maternal exposure to predator odour is sufficient to increase long-term energy mobilization in adult offspring. PMID- 29799026 TI - Author Correction: Defective Gpsm2/Galphai3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome. AB - This corrects the article DOI: 10.1038/ncomms14907. PMID- 29799025 TI - Hepatitis transactivator protein X promotes extracellular matrix modification through HIF/LOX pathway in liver cancer. AB - Hepatocellular carcinoma (HCC), accounting for 90% of primary liver cancer, is a lethal malignancy that is tightly associated with chronic hepatitis B virus (HBV) infection. HBV encodes a viral onco-protein, transactivator protein X (HBx), which interacts with proteins of hepatocytes to promote oncogenesis. Our current study focused on the interaction of HBx with a transcription factor, hypoxia inducible factor-1alpha (HIF-1alpha), which is stabilized by low O2 condition (hypoxia) and is found to be frequently overexpressed in HCC intra-tumorally due to poor blood perfusion. Here, we showed that overexpression of HBx by tetracycline-inducible systems further stabilized HIF-1alpha under hypoxia in HBV negative HCC cell lines. Reversely, knockdown of HBx reduced HIF-1alpha protein stabilization under hypoxia in HBV-positive HCC cell lines. More intriguingly, overexpression of HBx elevated the mRNA and protein expression of a family of HIF 1alpha target genes, the lysyl oxidase (LOX) family in HCC. The LOX family members function to cross-link collagen in the extracellular matrix (ECM) to promote cancer progression and metastasis. By analyzing the collagens under scanning electron microscope, we found that collagen fibers were significantly smaller in size when incubated with conditioned medium from HBx knockdown HCC cells as compared to control HCC cells in vitro. Transwell invasion assay further revealed that less cells were able to invade through the matrigel which was pre treated with conditioned medium from HBx knockdown HCC cells as compared to control HCC cells. Orthotopic and subcutaneous HCC models further showed that knockdown of HBx in HCC cells reduced collagen crosslinking and stiffness in vivo and repressed HCC growth and metastasis. Taken together, our in vitro and in vivo studies showed the HBx remodeled the ECM through HIF-1alpha/LOX pathway to promote HCC metastasis. PMID- 29799028 TI - Author Correction: Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium catalysed allylic arylation of racemates. AB - This corrects the article DOI: 10.1038/ncomms15762. PMID- 29799029 TI - Tenascin-C derived signaling induces neuronal differentiation in a three dimensional peptide nanofiber gel. AB - The development of new biomaterials mimicking the neuronal extracellular matrix (ECM) requires signals for the induction of neuronal differentiation and regeneration. In addition to the biological and chemical cues, the physical properties of the ECM should also be considered while designing regenerative materials for nervous tissue. In this study, we investigated the influence of the microenvironment on tenascin-C signaling using 2D surfaces and 3D scaffolds generated by a peptide amphiphile nanofiber gel with a tenascin-C derived peptide epitope (VFDNFVLK). While tenascin-C mimetic PA nanofibers significantly increased the length and number of neurites produced by PC12 cells on 2D cell culture, more extensive neurite outgrowth was observed in the 3D gel environment. PC12 cells encapsulated within the 3D tenascin-C mimetic peptide nanofiber gel also exhibited significantly increased expression of neural markers compared to the cells on 2D surfaces. Our results emphasize the synergistic effects of the 3D conformation of peptide nanofibers along with the tenascin-C signaling and growth factors on the neuronal differentiation of PC12 cells, which may further provide more tissue-like morphology for therapeutic applications. PMID- 29799030 TI - Composed in the f-block: solution structure and function of kinetically inert lanthanide(iii) complexes. AB - It has been more than 15 years since the last authoritative report on the solution structure of lanthanide complexes made from cylcen derived polydentate ligands. The field has progressed and diversified, and tools have been developed that should enable a step-change in the field in the imminent future. This will only happen if the tools are used, and the results communicated in a form that is consistent within the field and readily accesible to scientists outside the field. In this perspective, the fundamental tools for designing and investigating kinetically inert lanthanide complexes in solution will be covered. The fundamentals of this type of complexes will be laid out. The conformations of lanthanide complexes from cyclen derived ligands and the rate of exchange between conformations will be linked to their 1H NMR and luminescence spectra. The information rich ligand- and metal centred emission spectra will be discussed, and the time-resolved luminescence decay lifetimes are shown to be directly related to the solution structure. The aim is to provide the reader with the information needed to become excited by lanthanide coordination chemistry. PMID- 29799027 TI - Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. AB - BACKGROUND: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. METHODS: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. RESULTS: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 umol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 +/- 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 +/- 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 +/- 2.4 versus metabolic syndrome subjects to 1.2 +/- 4.1). CONCLUSIONS: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus. PMID- 29799031 TI - Solar light harvesting with multinary metal chalcogenide nanocrystals. AB - The paper reviews the state of the art in the synthesis of multinary (ternary, quaternary and more complex) metal chalcogenide nanocrystals (NCs) and their applications as a light absorbing or an auxiliary component of light-harvesting systems. This includes solid-state and liquid-junction solar cells and photocatalytic/photoelectrochemical systems designed for the conversion of solar light into the electric current or the accumulation of solar energy in the form of products of various chemical reactions. The review discusses general aspects of the light absorption and photophysical properties of multinary metal chalcogenide NCs, the modern state of the synthetic strategies applied to produce the multinary metal chalcogenide NCs and related nanoheterostructures, and recent achievements in the metal chalcogenide NC-based solar cells and the photocatalytic/photoelectrochemical systems. The review is concluded by an outlook with a critical discussion of the most promising ways and challenging aspects of further progress in the metal chalcogenide NC-based solar photovoltaics and photochemistry. PMID- 29799032 TI - In situ generation of 3D graphene-like networks from cellulose nanofibres in sintered ceramics. AB - Establishing a 3D electrically percolating network in an insulating matrix is key to numerous engineering and functional applications. To this end, using hydrophobic carbon nanofillers is tempting, but still results in suboptimal performance due to processing challenges. Here, we demonstrate how natural cellulose nanofibres can be in situ transformed into graphene-like sheets connected to a 3D network enhancing both the transport and the mechanical properties of sintered engineering ceramics. The network architecture also permits the decoupling of electrical and thermal conductivities, which represents a major obstacle in attaining efficient thermoelectric materials. We foresee that our transferable methodology can pave the way for the use of natural nanofibres to unravel the full potential of 3D graphene-like networks to accelerate development in fields like energy and telecommunications. PMID- 29799033 TI - Ring-expanded N-heterocyclic carbenes as ligands in iron-catalysed cross-coupling reactions of arylmagnesium reagents and aryl chlorides. AB - The structure-activity relationship of expanded-ring N-heterocyclic carbenes (NHCs) in the iron-catalysed Kumada aryl-aryl coupling reaction was explored. This was achieved by comparing the catalytic performance of Fe-NHC catalysts generated in situ containing NHCs that differ in steric bulk. In particular, the influences of ring sizes (5-8) and N-aryl substituents were explored in terms of spectroscopic and structural features, which affect their %Vbur values. The three best performing ligands were found on a diagonal of a 5 * 4 structural matrix revealing an optimal steric bulk and significant influences of subtle steric variations on the catalytic activities. PMID- 29799034 TI - Negative dendritic effect on enzymatic hydrolysis of dendrimer conjugates. AB - Dendrimers possess intriguing "dendritic effects", which are unique characteristics that stem from the dendrimer generation and size. Here we report a "negative dendritic effect" observed during enzymatic hydrolysis of dendrimer conjugates. Such negative dendritic effects, though rarely reported, may be explored for tailored and generation-dependent drug release. PMID- 29799035 TI - Carboxylic and O-acetyl moieties are essential for the immunostimulatory activity of glucuronoxylomannan: a novel TLR4 specific immunostimulator from Auricularia auricula-judae. AB - This study established the comprehensive repeating unit structure of immunologically active glucuronoxylomannan (AAPS) from wood ear mushroom, Auricularia auricula-judae. We identified Toll-like receptor 4 (TLR4) as a critical receptor involved in AAPS-induced macrophage activation to secrete pro inflammatory cytokines. Molecular modeling data and chemical modifications of AAPS revealed that both carboxylic and acetyl moieties of AAPS are equally essential in TLR4 binding to exert in vitro immunostimulatory activity. PMID- 29799036 TI - Mechano-responsive room temperature luminescence variations of boron conjugated pyrene in air. AB - Stimuli responsive tunable luminescence is a promising field of research. Even though mechanofluorescence is widely studied, mechanophosphorescence remains unexplored. Here we report the mechano-driven fluorescence and phosphorescence variations of a pyrene tetraboronic ester derivative. The fluorochromic and room temperature phosphorescence features are supported by theoretical studies and single crystal analysis. The mechanically ground fluorescence active but phosphorescence inactive pyrene tetraboronic ester exhibits room temperature phosphorescence in air with mechanical force. The efficient intermolecular electronic coupling in the dimer formed upon scratching enables a good communication between singlet and triplet states, hence resulting in room temperature mechanophosphorescence. PMID- 29799037 TI - Towards wireless highly sensitive capacitive strain sensors based on gold colloidal nanoparticles. AB - We designed, produced and characterized new capacitive strain sensors based on colloidal gold nanoparticles. The active area of these sensors, made up of a 1 mm2 close-packed assembly of gold nanoparticles between interdigitated electrodes, was designed to achieve measurable capacitance (>~1 pF) and overcome parasitic capacitances. Electro-mechanical experiments revealed that the sensitivity of such capacitive sensors increases in relation to the size of the nanoparticles. In the case of 14 nm gold NPs, such sensors present a relative capacitance variation of -5.2% for a strain of 1.5%, which is more than 5 times higher than that observed for conventional capacitive strain gauges. The existence of two domains (pure capacitive domain and mixed capacitive-resistance domain) as a function of the frequency measurement allows for the adaptation of sensitivity of these capacitive sensors. A simple low-cost circuit based on a microcontroller board was finally developed to detect the capacitance variations of such NP based strain sensors. This low-cost equipment paves the way for the development of an entirely wireless application set-up. PMID- 29799038 TI - Organocatalytic synthesis of densely functionalized oxa-bridged 2,6 epoxybenzo[b][1,5]oxazocine heterocycles. AB - Metal-free addition of salicylhydrazones to electron deficient internal alkynes catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) to yield oxa-bridged 2,6 epoxybenzo[b][1,5]oxazocine heterocycles was achieved. The demonstrated protocol proceeds through an o-quinone methide formation, aza-Michael addition, stereoselective protonation, enamine promoted aromatization, O,O-acetalization and O,N-aminalization sequence to provide privileged heterocycles in good yields with high diastereoselectivities. PMID- 29799039 TI - Effects of carbon-based impurities on graphene growth. AB - In this paper, we studied the growth of graphene on an untreated Cu substrate and further studied the effect of carbon-based impurities on the nucleation of graphene in different growth environments. It is found that the impurities on the surface of the Cu substrate easily lead to damage of the graphene, and the impurities do not always promote nucleation as previously reported, but inhibit nucleation in a high etching environment. Finally, based on experimental results, a model of nucleation and growth of graphene around impurities is presented. PMID- 29799040 TI - Conversion of methanol to propylene over hierarchical HZSM-5: the effect of Al spatial distribution. AB - Different silicon sources caused diverse Al spatial distribution in HZSM-5, and this affected the hierarchical structures and catalytic performance of desilicated zeolites. After being treated with 0.1 M NaOH, HZSM-5 zeolites synthesized with silica sol exhibited relatively widely distributed mesopores and channels, and possessed highly improved propylene selectivity and activity stability. PMID- 29799041 TI - Disentangling the photochemistry of benzocyclobutenedione. AB - The ultrafast photophysics and photochemistry of benzocyclobutenedione (BCBD) dissolved in dichloromethane is investigated by transient absorption spectroscopy in both the IR and the UV/Vis regime. The molecule is excited at 300 nm to the S3 (pipi*) state and a time scale from roughly 100 fs to several nanoseconds is covered. The initially excited S3 deactivates quickly to the lower-lying S1 (npi*) state. Three parallel photochemical reaction pathways starting in the S1 state that compete with deactivation to S0 are identified in the transient IR spectra, two of them consisting of a sequence of steps. DFT/TDDFT calculations of the normal modes of the reactant and various photoproducts support the analysis of the transient spectra. The rapid internal conversion (IC) to the S1 state of BCBD is followed by a sub-picosecond vibrational relaxation (VR) to S1 (nu = 0). In parallel BCBD loses one carbonyl group and forms benzocyclopropenone, which subsequently rearranges to cyclopentadienylidene ketene. Ring opening in the S1 (nu = 0) state produces vibrationally hot bisketene, which cools within 22 ps. This reaction competes with the intramolecular rearrangement to singlet oxacarbene, which subsequently converts into the triplet carbene via intersystem crossing (ISC). The late-time product identified in the transient UV/Vis spectra is probably due to dimerization of the carbene. Molecular dynamics (MD) simulations of the early-time photochemistry of BCBD successfully reproduce the formation of the three main photoproducts. PMID- 29799042 TI - Improvements in the hydrogen storage properties of the Mg(NH2)2-LiH composite by KOH addition. AB - Potassium-containing compounds, such as KH, KOH, KNH2 and different potassium halides, have shown positive effects on the dehydrogenation properties of the Li Mg-N-H system. However, it is still discussed whether the K-compounds modify the thermodynamics of the system or if they have only a catalytic effect. In this work the impact of the addition of two K-containing compounds (0.08 mol% of KCl and KOH) on the hydrogen storage performance of the Mg(NH2)2-LiH composite was studied. The KOH incorporation reduced the dehydrogenation temperature from 197 degrees C to 154 degrees C, beginning the process at low temperature (~70 degrees C). The doped sample was able to reversibly absorb and desorb 4.6 wt% of hydrogen with improved kinetics; dehydrogenation rates were increased four times, whereas absorptions required 20% less time to be completed in comparison to the pristine material. The thermodynamic destabilization of the Mg(NH2)2-2LiH composite by the addition of a small amount of KOH was demonstrated by an increment of 30% in the dehydrogenation equilibrium pressure. According to detailed structural investigations, the KH formed by the KOH decomposition through milling and thermal treatment, can replace LiH and react with Mg(NH2)2 to produce a mixed potassium-lithium amide (Li3K(NH2)4). The KH role is not limited to catalysis, but rather it is responsible for the thermodynamic destabilization of the Mg(NH2)2-LiH composite and it is actively involved in the dehydrogenation process. PMID- 29799043 TI - Thermodynamics and defect chemistry of substitutional and interstitial cation doping in layered alpha-V2O5. AB - A systematic study of the location and energetics of cation dopants in alpha-V2O5 has been conducted using pair-potential methods, supplemented by first-principles calculations. The consequences of doping on intrinsic defect equilibria have been discussed and the effects of selected dopants on Li+ and Mg2+ diffusion energy barriers have been investigated. PMID- 29799044 TI - Nucleophilic addition of tertiary propargylic amines to arynes followed by a [2,3]-sigmatropic rearrangement. AB - In the presence of 2-(trimethylsilyl)aryl triflates as aryne precursors under mild conditions, a range of tertiary propargylic amines bearing electron withdrawing groups were converted to quaternary propargylic ammonium ylides followed by a [2,3]-sigmatropic rearrangement to afford structurally diverse amino-substituted allenes or conjugated dienes, depending on their structure, in moderate to good yields. PMID- 29799045 TI - Carbene-catalyzed enal gamma-carbon addition to alpha-ketophosphonates for enantioselective access to bioactive 2-pyranylphosphonates. AB - A carbene-catalyzed enantioselective [4+2] cycloaddition reaction between alpha,beta-unsaturated aldehydes and alpha-ketophosphonates is developed. The reaction affords chiral 2-pyranylphosphonates with excellent enantioselectivities. The optically enriched phosphonate products bear multiple functional groups, including unsaturated lactone and phosphonate moieties that often lead to unique bio-activities. Preliminary studies show that the products from our reactions exhibit anti-bacterial (X. oryzae pv. oryzae) and anti-viral (Tobacco Mosaic Virus) activities for potential use in plant protection. PMID- 29799046 TI - Nano-designed semiconductors for electro- and photoelectro-catalytic conversion of carbon dioxide. AB - Development of novel catalysts with high efficiency for CO2 conversion is of great research interest, because of the climate hazards caused by the gradual increase in CO2 concentration. Among various types of catalysts, semiconductors have been widely used as effective candidates for both electro- and photoelectro CO2 conversion. Very recently, with the emerging nanotechnology and advanced characterization techniques, tremendous achievements have been made in highly efficient and clean CO2 conversion based on semiconductor catalysts. This review gives a systematic overview of this field, including the rational design of semiconductor catalysts for electro- and photoelectro-chemical CO2 conversion. Recent advances in the development of mechanism understandings on reaction pathways of CO2 and the feasibility for industrial production are discussed. Furthermore, the challenges and future perspectives of electro- and photoelectro catalytic CO2 conversion are outlined. PMID- 29799047 TI - The blocking effect of surface dislocations on oxygen tracer diffusion in SrTiO3. AB - The existence of a polishing-induced damaged zone at the surface of standard, nominally undoped, single-crystal SrTiO3 is exploited in diffusion studies in order to investigate the interaction between oxygen vacancies and dislocations. Tracer diffusion profiles for such crystals are proposed to exhibit three features: a short feature arising from a surface space-charge layer; an intermediate, longer feature arising from the high density of dislocations in the damaged zone; and finally, a much longer feature corresponding to diffusion in the homogeneous bulk crystal. Quantitative information is provided by finite element-method calculations. First, the distribution of oxygen vacancies in a sample in which space-charge zones depleted of oxygen vacancies form at dislocations and at the sample surface is calculated; subsequently, oxygen tracer diffusion profiles for such vacancy distributions are simulated. The proposed model is experimentally validated by performing conventional oxygen isotope exchange and depth-profiling experiments on commercial single-crystal SrTiO3. In this way, we confirm directly that arrays of dislocations in acceptor-doped SrTiO3, by virtue of the attendant space-charge tubes, hinder the diffusion of oxygen. Finally, in order to aid the prediction of oxygen tracer diffusion profiles in polished perovskite single-crystal substrates, we suggest a one dimensional continuum approach that takes account of the complex, three dimensional diffusion problem posed by dislocation arrays with depletion space charge tubes. PMID- 29799048 TI - Ecology and evolution of metabolic cross-feeding interactions in bacteria. AB - Literature covered: early 2000s to late 2017Bacteria frequently exchange metabolites with other micro- and macro-organisms. In these often obligate cross feeding interactions, primary metabolites such as vitamins, amino acids, nucleotides, or growth factors are exchanged. The widespread distribution of this type of metabolic interactions, however, is at odds with evolutionary theory: why should an organism invest costly resources to benefit other individuals rather than using these metabolites to maximize its own fitness? Recent empirical work has shown that bacterial genotypes can significantly benefit from trading metabolites with other bacteria relative to cells not engaging in such interactions. Here, we will provide a comprehensive overview over the ecological factors and evolutionary mechanisms that have been identified to explain the evolution and maintenance of metabolic mutualisms among microorganisms. Furthermore, we will highlight general principles that underlie the adaptive evolution of interconnected microbial metabolic networks as well as the evolutionary consequences that result for cells living in such communities. PMID- 29799049 TI - Quantitative description of 1H SQ and DQ coherences for the hydroxyl disorder within hydrous ringwoodite. AB - Proton-containing point defects in solid materials are important for a variety of properties ranging from ionic transport over thermal conductivity up to compressibility. Ultrafast magic-angle spinning techniques nowadays offer high resolution solid-state NMR spectra, even for 1H, and thus open up possibilities to study the underlying defect chemistry. Nevertheless, disorder within such defects again leads to heavy spectral overlap of 1H resonances, which prevents quantitative analysis of defect concentrations, if several defect types are present. Here, we present a strategy to overcome this limitation by simulating the 1H lineshape as well as 1H-1H double-quantum buildup curves, which we then validate against the experimental data in a joint cost function. To mimic the local structural disorder, we use molecular dynamics simulations at the DFT level. It turned out to be advantageous for the joint refinement to put the computational effort into the structural optimisation to derive accurate proton positions and to use empirical correlations for the relation between isotropic and anisotropic 1H chemical shifts and structural elements. The expressiveness of this approach is demonstrated on ringwoodite's (gamma-Mg2SiO4) OH defect chemistry containing four different defect types in octahedral and tetrahedral voids with both pure Mg and mixed Si and Mg cation environments. Still, we determine the ratio for each defect type with an accuracy of about 5% as a result of the minimization of the joint cost function. We expect that our approach is generally applicable for local proton disorder and might prove to be a valuable alternative to the established AIRSS and Monte Carlo methods, respectively. PMID- 29799050 TI - Intermediate length-scale chirality related to the vibrational circular dichroism intensity enhancement upon fibril formation in a gelation process. AB - Chiro-optical spectroscopic methods, such as vibrational circular dichroism (VCD) spectroscopy, are regarded as useful measures that provide us information on the structural properties of chiral species, but for correct interpretation of the measured spectra, appropriate modeling that can be compared with the observed spectra is essential. In the present study, the origin of the VCD intensity enhancement observed upon fibril formation in a gelation process is examined theoretically. Comparing with the observed spectroscopic feature and also with the observed scanning electron microscope (SEM) image, it is derived that there are at least three hierarchical tiers of chirality in the gel. The VCD intensity enhancement originates from one of them on the ~50 nm length scale, which consists of a co-axial antiparallel right-handed double helical structure that persistently continues over ~100 molecules, indicating that the intermediate length-scale fibril formation plays a crucial role in the VCD intensity enhancement, in a way similar to some fibril-forming peptides examined previously. The time course of the gelation process observed by the time dependence of the VCD intensity is also shown and discussed. PMID- 29799051 TI - Synthesis of distorted nanographenes containing seven- and eight-membered carbocycles. AB - This feature article focuses on the bottom-up approaches (solution-phase) based on organic synthesis for the preparation of saddle-shaped distorted polycyclic aromatic hydrocarbons (PAHs). We summarise the recent progress on the synthetic strategies followed to obtain well-defined nanographenes containing heptagonal and octagonal carbocycles, highlighting the novel strategy developed by our group together with our recent contributions in the area of distorted aromatics. The presence of seven- or eight-membered rings induces a saddle-shape curvature in the planar network pushing the structure out of the plane, which influences the physical properties exhibited. Some brief details on the optical and electronic properties of these curved nanostructures are also discussed. PMID- 29799052 TI - All-inorganic perovskite quantum dot/TiO2 inverse opal electrode platform: stable and efficient photoelectrochemical sensing of dopamine under visible irradiation. AB - CsPbX3 (X = Cl, Br or I) perovskite quantum dots (PQDs) have attracted tremendous attention due to their extraordinarily excellent optical properties. However, there is still an obstacle for their bio-application, which is limited by their water-instability. In this work, we have designed a novel visible light triggered photoelectrochemical (PEC) sensor for dopamine (DA) based on CsPbBr1.5I1.5 PQD immobilized three-dimensional (3D) TiO2 inverse opal photonic crystals (IOPCs). Supported by the TiO2 IOPCs, the water-stability of the PQDs as well as that of the PEC sensor was considerably improved. Furthermore, employed as a photoactive material in PEC sensor, CsPbBr1.5I1.5 PQDs can expand the photocurrent response of the PEC sensor to the whole visible region. In addition, the modulation of the photonic stop band effect of TiO2 IOPCs on the incident light and the emission of PQDs could further enhance the photocurrent response. Such a PEC sensor demonstrates sensitive detection of DA in phosphate buffer saline solution and serum, with a good linear range from 0.1 MUM to 250 MUM and a low detection limit of approximately 0.012 MUM. Our strategy opens an alternative horizon for PQD based PEC sensing, which could be more sensitive, convenient and inexpensive for clinical and biological analysis. PMID- 29799053 TI - Active cargo transport with Janus colloidal shuttles using electric and magnetic fields. AB - Active colloids show non-equilibrium behavior that departs from classical Brownian motion, thus providing a platform for novel fundamental phenomena and for enticing possible applications ranging from water treatment to medicine and microrobotics. Although the physics, motion mechanisms and guidance have been extensively investigated, active colloids are rarely exploited to simultaneously guide and transport micron-sized objects in a controllable and reversible manner. Here, we use autonomous active Janus particles as colloidal shuttles to controllably transport cargo at the microscale using external electric and magnetic fields. The active motion arises from the metallodielectric characteristics of the Janus particles, which allows them to also trap, transport and release cargo particles through dielectrophoretic interactions induced by an AC electric field. The ferromagnetic nature of the nickel layer that forms the metallic hemisphere of the Janus colloids provides an additional mechanism to direct the motion of the shuttle using an external magnetic field. With this highly programmable colloidal system, we are able to harness active colloid motion and use it to transport cargo particles to specific destinations through a pre-defined route. A simple analytical model is derived to successfully describe the motion of the shuttle-cargo assembly in response to the applied electrical field. The high level of control on cargo pick-up, transport and release leads to a powerful delivery tool, which could eventually be used in microactuators, microfluidics or for controlled delivery within organ-on-a-chip devices. PMID- 29799054 TI - Clinics in diagnostic imaging (186). Atrial septal defect with pulmonary arterial hypertension. AB - We report a case of a 61-year-old woman with a large atrial septal defect (ASD) that was detected incidentally on chest radiography and computed tomography when she presented with sepsis. Echocardiography confirmed a large secundum ASD with left-to-right shunt flow, right heart dilatation and severe pulmonary hypertension. The patient had a poor clinical outcome despite intensive care and eventually passed away. Haemodynamically significant ASDs have a known association with increased morbidity and mortality, and their early detection and closure cannot be understated. This article aimed to highlight the imaging features of ASD, with special emphasis on the routine chest radiograph. The pathophysiology and clinical manifestations of ASD are also briefly discussed. PMID- 29799055 TI - Approach to frailty in the elderly in primary care and the community. AB - Frailty is a distinct clinical syndrome wherein the individual has low reserves and is highly vulnerable to internal and external stressors. Although it is associated with disability and multiple comorbidities, it can also be present in individuals who seem healthy. Frailty is multidimensional and its pathophysiology is complex. Early identification and intervention can potentially decrease or reverse frailty, especially in the early stages. Primary care physicians, community nurses and community social networks have important roles in the identification of pre-frail and frail elderly through the use of simple frailty screening tools and rapid geriatric assessments. Appropriate interventions that can be initiated in a primary care setting include a targeted medical review for reversible medical causes of frailty, medication appropriateness, nutritional advice and exercise prescription. With ongoing training and education, the multidisciplinary engagement and coordination of care of the elderly in the community can help to build resilience and combat frailty in our rapidly ageing society. PMID- 29799056 TI - Comment on: Medication-related osteonecrosis of the jaw in osteoporotic patients: prevention and management. PMID- 29799057 TI - Comment on: Cytomegalovirus (CMV) hepatitis: an uncommon complication of CMV reactivation in drug reaction with eosinophilia and systemic symptoms. PMID- 29799058 TI - Comment on: Haematologist-reviewed peripheral blood smear in paediatric practice. PMID- 29799059 TI - Questionnaire survey on adjuvant chemotherapy for elderly patients after gastrectomy indicates their vulnelabilities. AB - BACKGROUND: In Japan, S-1 adjuvant chemotherapy for 1 year is the standard of care for the treatment of stage II and III patients under 80 years old with gastric cancer after curative operation. However, the feasibility of S-1 chemotherapy in patients over 80 years old has not yet been elucidated. METHODS: To clarify the current treatment situation and feasibility of S-1 treatment in patients over 80 years old, a questionnaire survey of the patients treated from January 2011 to December 2012 was conducted at 58 member institutions of the Stomach Cancer Study Group of the JCOG (Japan Clinical Oncology Group). RESULTS: Gastrectomy was performed in 15,573 patients of all ages, and 1,660 (10.7%) patients were over 80 years of age. Of these elderly patients, 661 (4.2%) were diagnosed as stage II and III. While S-1 adjuvant chemotherapy was recommended to 248 (37.5%) of the stageII/III patients, only 99 (15.0%) of them actually received S-1. Interestingly, the creatinine clearance rate was between 30 and 80 mL/min in 87 (87.9%) of the patients suggesting that S-1 dose modification should be considered. Moreover, S-1 compliance was poor in patients with more than 15% body weight loss. CONCLUSION: In general practice, surgery alone can be regarded as the standard of care for stage II and III gastric cancer patients over 80 years old. The feasibility and efficacy of S-1 adjuvant chemotherapy should be elucidated in a randomized control trial considering the vulnerabilities of the elderly. PMID- 29799060 TI - Risk factors for lymph node metastasis in non-sentinel node basins in early gastric cancer: sentinel node concept. AB - BACKGROUND: Sentinel node (SN) concept is being applied to early gastric cancer. However, when SNs are positive for metastasis, it is unclear how often LNs in other LN basins show metastasis. We aimed to investigate LN metastasis possibility in LN basins without SNs (non-SN basins). We determined risk factors for metastasis in non-SN basins and identified a prediction model for non-SN basin metastasis using classification and regression tree (CART) analysis. METHODS: We enrolled 550 patients who were diagnosed with cT1N0M0 or cT2N0M0 gastric cancer with a single lesion and underwent SN mapping. We adopted a dual tracer method using a radioactive colloid and blue dye to detect SNs. RESULTS: Of all, 45 (8.2%) patients had SN metastasis; we divided them into two groups: LN metastasis positive and LN metastasis negative in non-SN basins. Univariate analysis showed that the groups differed significantly regarding lymphatic invasion (p = 0.007), number of identified SNs (p = 0.032), and macrometastasis in SN basins (p = 0.005). The CART decision tree for predicting LN metastasis in non-SN basins had area under the curve value of 0.86. Moreover, there were significantly differences in cancer-specific survival (CSS) between the two groups (p = 0.028). CONCLUSIONS: Macrometastasis in SN basins, lymphatic invasion, and number of identified SNs >= 5 are risk factors for LN metastasis in non-SN basins among gastric cancer patients. We identified a prediction model with CART analysis; patients with macrometastasis in SN basins and lymphatic invasion were considered to be at the highest risk for LN metastasis. PMID- 29799063 TI - Erupted coronary atheroma: insights from multi-modality imaging. AB - A 58-year-old gentleman with prolonged chest pain and 20-min ST-segment elevation in inferior lead on Holter monitoring was hospitalized. Multi-slice computed tomography identified severe stenosis with low density area and positive remodeling. Despite the suggestive features of vulnerable lesion, intravascular ultrasound and near-infrared spectroscopy imaging identified ruptured plaque without any lipidic material which were contrary to findings from multi-slice computed tomography. Lipidic materials may travel into coronary circulation following its spontaneous rupture, resulting in zero lipid core burden index. Multi-modality imaging has the potential to elucidate the pathophysiology of eruption of coronary atheroma in vivo. PMID- 29799062 TI - Right ventricular function and mechanics in chemotherapy- and radiotherapy-naive cancer patients. AB - The present research evaluated right ventricular (RV) structure, function and mechanics in the cancer patients before initiation of chemo- or radiotherapy, and the association between cancer and decreased RV longitudinal strain. This retrospective investigation included 101 chemo- and radiotherapy-naive patients with solid cancer and 38 age- and gender-matched controls with similar cardiovascular risk profile. Echocardiographic examination and strain evaluation was performed in all participants. RV structure and RV systolic and diastolic function estimated with conventional echocardiographic parameters were similar between the cancer patients and controls. However, RV global longitudinal strain (- 22.7 +/- 2.6% vs. - 21.1 +/- 2.4%, p < 0.001) was significantly decreased in the cancer patients than in controls. The same was revealed for RV free wall endocardial (- 33.6 +/- 4.3% vs. - 31.4 +/- 4.0%, p = 0.006) and mid-myocardial ( 25.2 +/- 3.6% vs. - 23.7 +/- 3.8%, p = 0.035) longitudinal RV strains, whereas difference was not found in RV free wall epicardial longitudinal strain. The presence of cancer was independently of age, gender, body mass index, left ventricular hypertrophy, diabetes, hypertension and pulmonary pressure associated with reduced RV global longitudinal strain (OR 3.79; 95% CI 2.18-10.92, p < 0.001), as well as with decreased free wall RV longitudinal strain (OR 5.73; 95% CI 3.17-9.85, p < 0.001). RV strain is deteriorated in the chemo- and radiotherapy-naive cancer patients. Endocardial and mid-myocardial layers are more affected than epicardial strain in the cancer patients. The presence of cancer is independently of other clinical parameters associated with reduced RV longitudinal strain. PMID- 29799061 TI - Quantification of aortic stiffness in stroke patients using 4D flow MRI in comparison with transesophageal echocardiography. AB - To quantify stiffness of the descending aorta (DAo) in stroke patients using 4D flow MRI and compare results with transesophageal echocardiography (TEE). 48 acute stroke patients undergoing 4D flow MRI and TEE were included. Intima-media thickness (IMT) was measured in the DAo and the aorta was scrutinized for atherosclerotic plaques using TEE. Stiffness of the DAo was determined by (a) 4D flow MRI at 3 T by calculating pulse wave velocity (PWV) and by (b) TEE calculating arterial strain, stiffness index, and distensibility coefficient. Mean IMT was 1.43 +/- 1.75. 7 (14.6%) subjects had no sign of atherosclerosis, 10 (20.8%) had IMT-thickening or plaques < 4 mm, and 31 (66.7%) had at least one large and/or complex plaque in the aorta. Increased IMT significantly correlated (p < 0.001) with increased DAo stiffness in MRI (PWV r = 0.66) and in TEE (strain r = 0.57, stiffness index r = 0.64, distensibility coefficient r = 0.57). Patients with at least IMT-thickening had significantly higher stiffness values compared to patients without atherosclerosis. However, no difference was observed between patients with plaques < 4 mm and patients with plaques >= 4 mm. PWV and TEE parameters of stiffness correlated significantly [strain (r = - 0.36; p = 0.011), stiffness index (r = 0.51; p = 0.002), and distensibility coefficient (r = - 0.59; p < 0.001)]. 4D flow MRI and TEE-based parameters of aortic stiffness were associated with markers of atherosclerosis such as IMT-thickness and presence of plaques. We believe that 4D flow MRI is a promising tool for future studies of aortic atherosclerosis, due to its longer coverage of the aorta and non-invasiveness. PMID- 29799064 TI - Investigation of elastic features of aorta and color M-mode flow propagation velocity (APV) of descending aorta in the patients with ischemic and non-ischemic dilated cardiomyopathy. AB - Aortic flow propagation velocity (APV) is a novel echocardiographic parameter used in coronary artery disease. It has also been used for the evaluation of aortic stiffness. In the present study, APV was measured in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM) and was compared with the parameters of aortic stiffness such as aortic distensibility (AD) and aortic strain (AS). A total of 140 patients who had undergone coronary angiographic imaging were included in the study. Out of these patients, 44 had ischemic DCM, 46 had non-ischemic DCM, and 50 had normal coronary angiography (control group). AS, AD, and APV were calculated echocardiographically. One-way analysis of variance (ANOVA) and the Kruskal-Wallis test were used to compare continuous variables between the groups, while the categorical variables were compared using Pearson's Chi square test. Pearson's correlation test was used to investigate the parameters associated with APV, AS, and AD. Ischemic DCM and non-ischemic DCM groups differed significantly. The comparison of these groups with the control group, in terms of AS, AD, and APV values (ANOVA p < 0.001 for all) also showed a significant difference. APV was found to be significantly correlated with AS (r = 0.645, p < 0.001) and AD (r = 0.604, p < 0.001). In ROC analysis, the area under the curve (AUC) value for APV was 0.999 (p = 0.000) for detection of patients ischemic DCM and non-ischemic DCM. APV may be considered to be a novel and a simple echocardiographic marker, for both, distinguishing ischemic from non ischemic DCM as well as for the presence of dilated cardiomyopathy with or without critical coronary artery disease. PMID- 29799065 TI - Correction to: No difference in mid-term survival and clinical outcome between patient-specific and conventional instrumented total knee arthroplasty: a randomized controlled trial. AB - In the original article, one of the co-author's (W. van der Weegen) middle name has been missed in the publication of the article. The correct complete name should be W. van der Weegen. PMID- 29799068 TI - A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI. PMID- 29799066 TI - Genome characteristics dictate poly-R-(3)-hydroxyalkanoate production in Cupriavidus necator H16. AB - Cupriavidus necator H16 is a well-recognized enterprise with efficient manufacturing machineries to produce diverse polymers belonging to polyhydroxyalkanoates (PHAs) family. The genome fingerprints, including PHA machinery proteins and fatty acid metabolism, had educated engineering strategies to enhance PHAs production. This outstanding progress has enlightened us to present an exhaustive examination of the ongoing research, addressing the great potential design of genome features towards PHA production and furthermore, we show how those acquired knowledge have been explored in other biotechnological applications. This updated-review concludes that the combination of an optimal strain selection, suitable metabolic engineering and a large-scale fermentation on oil substrates is critical to endow the ability of incorporating mcl-PHAs monomers in this organism. PMID- 29799069 TI - The history of hexachlorobenzene accumulation in Svalbard fjords. AB - In the present study, we investigated the spatial and historical trends of hexachlorobenzene (HCB) contamination in dated sediments of three Svalbard fjords (Kongsfjorden, Hornsund, Adventfjorden) differing in environmental conditions and human impact. HCB concentrations ranging from below limit of quantification (6.86 pg/g d.w.) to 143.99 pg/g d.w. were measured. The highest concentrations were measured in two surface sediment layers of the core collected in Hornsund near the melting glacier. The lowest concentrations of HCB were measured in Adventfjorden, suggesting that local source of HCB is not significant and global transport processes are the major transport pathways. The history of HCB deposition did not fully reflect the history of HCB emission (largest in 1950s and 1960s). In case of several sediment cores, the HCB enrichment in surface (recent) sediments was noticed. This can indicate importance of secondary sources of HCB, e.g., the influx of HCB accumulated over decades on the surface of glaciers. Detected levels of HCB were generally low and did not exceed background concentration levels; thus, a negative effect on benthic organisms is not expected. PMID- 29799070 TI - Revisiting the stress paradigm for silica nanoparticles: decoupling of the anti oxidative defense, pro-inflammatory response and cytotoxicity. AB - Engineered amorphous silica nanoparticles (nanosilica) are widely used in industry yet can induce adverse effects, which might be classified according to the oxidative stress model. However, the underlying mechanisms as well as the potential interactions of the three postulated different tiers of toxicity-i.e. oxidative-, pro-inflammatory- and cytotoxic-stress response-are poorly understood. As macrophages are primary targets of nanoparticles, we used several macrophage models, primarily murine RAW264.7 macrophages, and monitored pro inflammatory and anti-oxidative reactions as well as cytotoxicity in response to nanosilica at max. 50 ug/mL. Special attention was given to the activation of mitogen-activated protein kinases (MAPKs) as potential regulators of the cellular stress response. Indeed, according to the oxidative stress model, also nanosilica elicits an, albeit modest, anti-oxidative response as well as pronounced pro inflammatory reactions and cytotoxicity in macrophages. Interestingly however, these three tiers of toxicity seem to operate separately of each other for nanosilica. Specifically, impeding the anti-oxidative response by scavenging of reactive oxygen species does not prevent the pro-inflammatory and cytotoxic response. Furthermore, blocking the pro-inflammatory response by inhibition of MAPKs does not impair cell death. As hazard assessment has been guided by the prevailing assumption of a dose-dependent coupling of sequential tiers of toxicity, identification of critical physico-chemical parameters to assist the safe-by-design concept should be enabled by simply monitoring one of the toxicity read-outs. Our results indicate a more complex scenario in the case of nanosilica, which triggers independent pleiotropic effects possibly also related to different material properties and primary cellular targets. PMID- 29799067 TI - Recommendations on nuclear and multimodality imaging in IE and CIED infections. AB - In the latest update of the European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE), imaging is positioned at the centre of the diagnostic work-up so that an early and accurate diagnosis can be reached. Besides echocardiography, contrast-enhanced CT (ce-CT), radiolabelled leucocyte (white blood cell, WBC) SPECT/CT and [18F]FDG PET/CT are included as diagnostic tools in the diagnostic flow chart for IE. Following the clinical guidelines that provided a straightforward message on the role of multimodality imaging, we believe that it is highly relevant to produce specific recommendations on nuclear multimodality imaging in IE and cardiac implantable electronic device infections. In these procedural recommendations we therefore describe in detail the technical and practical aspects of WBC SPECT/CT and [18F]FDG PET/CT, including ce-CT acquisition protocols. We also discuss the advantages and limitations of each procedure, specific pitfalls when interpreting images, and the most important results from the literature, and also provide recommendations on the appropriate use of multimodality imaging. PMID- 29799071 TI - The central role of the pathologist in the management of patients with cervical cancer: ESGO/ESTRO/ESP guidelines. AB - The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) nominated an international multidisciplinary development group consisting of practicing clinicians who have demonstrated leadership and expertise in cervical cancer to produce evidence-based guidelines regarding all aspects of the management of patients with this disease. Herein, we provide a detailed analysis of the pathological reporting of cervical carcinoma specimens, focusing on practical aspects of specimen sampling and on the core pathological data which are critical for patient management. PMID- 29799072 TI - Context-induced relapse after extinction versus punishment: similarities and differences. AB - Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drug-reinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies. PMID- 29799074 TI - Effects of water shortage in Kabul River network on the plain areas of Khyber Pakhtunkhwa, Pakistan. AB - Kabul River is a shared resource of Pakistan and Afghanistan and is a major source of economy for both countries. It is used for irrigation, power generation, fishery, hunting, and recreation. This study explored human-induced impact on Kabul River and its associated wetlands. For an in-depth study, the area situated between the two tributaries of Kabul River, i.e., Shalam and Naguman Rivers, was selected. The focus of the study was to find out reduction in the wetland areas, its causes, and associated impacts. For this purpose, a survey was conducted in 10 villages selected randomly in 10 union councils. The study revealed that anthropogenic activities, such as wetland farming, grazing residential encroachment, and industrial development, have caused severe alteration in the wetland of the study areas. The results revealed that before the 1990s, 33.55% area of the study area was wetland. Due to regular decrease in the flow of the Kabul River System and human encroachment, it has engulfed 68.40% of the total wetland leaving behind only 10.60% wetland. This can be termed as a big ecological disturbance. In the long run, this will have negative effects on both the countries. It is therefore recommended to give proper attention to this important wetland, positioning between Shalam and Naguman Rivers and to conserve it. One of the solutions is to regulate the natural flow of Kabul River. PMID- 29799075 TI - Effect of fixation devices on postoperative pain after laparoscopic ventral hernia repair: a randomized clinical trial of permanent tacks, absorbable tacks, and synthetic glue. AB - PURPOSE: The method of anchoring the mesh in laparoscopic ventral hernia repair is claimed to cause postoperative pain, affecting the quality of life of the patients. The aim of this randomized study was to compare the effect of three types of fixation devices on postoperative pain, patient quality of life, and hernia recurrence. METHODS: Patients with ventral hernias between 2 and 7 cm were randomized into one of three mesh fixation groups: permanent tacks (ProtackTM), absorbable tacks (SecurestrapTM), and absorbable synthetic glue (GlubranTM). The primary endpoint was pain on the second postoperative day, measured on a visual analogue scale. Quality of life and recurrence rate were secondary endpoints and investigated through questionnaires and clinical examination at follow-up visits 1, 6, and 12 months after surgery. RESULTS: Seventy-five non-consecutive patients were included in the study, with 25 patients in each group. There was no significant difference between groups for unspecified pain on the second postoperative day (p = 0.250). The DoloTestTM values were 55.3 +/- 28.9 mm, 43.5 +/- 28.5 mm, and 55.9 +/- 26.3 mm for permanent tacks, absorbable tacks, and synthetic glue, respectively. No differences were observed between groups with respect to quality of life of the patients and hernia recurrence rate. CONCLUSIONS: In patients with small- and medium-sized ventral hernias, the type of fixation device did not affect the immediate or long-term postoperative pain, quality of life, or recurrence rate when comparing permanent tacks, absorbable tacks, and synthetic glue for mesh fixation. TRIAL REGISTRATION: NCT01534780. PMID- 29799073 TI - Healthy ageing: the natural consequences of good nutrition-a conference report. AB - Many countries are witnessing a marked increase in longevity and with this increased lifespan and the desire for healthy ageing, many, however, suffer from the opposite including mental and physical deterioration, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental for good health, it remains unclear what impact various dietary interventions may have on prolonging good quality of life. Studies which span age, geography and income all suggest that access to quality foods, host immunity and response to inflammation/infections, impaired senses (i.e., sight, taste, smell) or mobility are all factors which can limit intake or increase the body's need for specific micronutrients. New clinical studies of healthy ageing are needed and quantitative biomarkers are an essential component, particularly tools which can measure improvements in physiological integrity throughout life, thought to be a primary contributor to a long and productive life (a healthy "lifespan"). A framework for progress has recently been proposed in a WHO report which takes a broad, person-centered focus on healthy ageing, emphasizing the need to better understand an individual's intrinsic capacity, their functional abilities at various life stages, and the impact by mental, and physical health, and the environments they inhabit. PMID- 29799076 TI - T-lymphocyte profiles differ between keratoacanthomas and invasive squamous cell carcinomas of the human skin. AB - BACKGROUND: T-lymphocytes are involved in tumor progression and regression. Actinic keratoses (AK) are atypical proliferations of keratinocytes of the skin. Some AK progress into invasive cutaneous squamous cell carcinomas (cSCC). Keratoacanthomas (KA) are either classified as a cSCC subtype or a benign tumor with histologic resemblance to well-differentiated cSCC as it is supposed to regress spontaneously. In contrast, cSCC represent malignant tumors that may metastasize. OBJECTIVES: To compare the T-lymphocyte profiles of AK, KA and cSCC in relation to PD-L1 expression. METHODS: Tissue micro-arrays of 103 cases of AK, 43 cases of KA and 106 cases of cSCC were stained by immunohistochemistry for E cadherin, CD3, CD4, CD8, FOXp3, and the receptor-ligand pair PD-1/PD-L1. Immunohistological scores were computationally determined to assess PD-L1 expression as well as the expression profiles of T-lymphocytes. RESULTS: AK had lower numbers of CD3+ and PD-1+ cells compared to KA and lower numbers of CD3+, CD8+ and PD-1+ cells in comparison with cSCC. KA showed significantly higher numbers of CD4+ and FOXp3+ cells as well as lower numbers of CD8+ cells in comparison with invasive cSCC. cSCC expressed significantly more PD-L1 in comparison with AK and KA. Among cSCC PD-L1 expression was higher in moderately and poorly-differentiated cSCC than in well-differentiated cSCC. Increased PD-L1 expression also correlated with increased numbers of CD4+, CD8+ and FOXp3+ cells in cSCC. CONCLUSIONS: Tumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC. PMID- 29799078 TI - Treatment of infra-isthmal femoral fracture with an intramedullary nail: Is retrograde nailing a better option than antegrade nailing? AB - INTRODUCTION: Antegrade intramedullary (IM) nailing is ideal for femoral shaft fractures, but fixing the fracture distal to the isthmal level may be difficult because of medullary canal widening and the proximity of fracture location from the distal femoral joint line. This study aimed to compare treatment results between antegrade and retrograde nailing for infra-isthmal femoral shaft fracture, and to identify influencing factors of nonunion and malalignment. MATERIALS AND METHODS: Sixty patients with infra-isthmal femoral shaft fractures treated with IM nailing and followed-up for > 1 year were enrolled in this retrospective study, 38 in the antegrade nailing group, and 22 in the retrograde nailing group. The two groups had no significant differences in age, sex, and fracture location (p = 0.297, Mann-Whitney test). Radiological evaluation was performed, and functional result was assessed using the Knee Society scoring system. Complications were analyzed in accordance with fracture location, fracture type, and operative method. RESULTS: According to the AO/OTA classification, 35, 16, and 9 cases were type A (A1: 1, A2: 11, A3: 23), B (B1: 2, B2: 7, B3: 7), and C fractures (C2: 4, C3: 5), respectively. The mean follow up duration was 29.5 months. In the antegrade and retrograde nailing groups, the primary bony union rates were 73.7% in 20.7 weeks (range 12-41) and 86.4% in 17.4 weeks (range 12-30), respectively. The two groups showed no significant differences in union rate (p = 0.251, Pearson's Chi-square test) and union time (p = 0.897, Mann-Whitney test). No cases of malalignment of > 10 degrees in any plane were found in both groups. The mean Knee Society scores were 92 (range 84 100) and 91 (range 83-95) in the antegrade and retrograde nailing groups, respectively, showing no significant difference (p = 0.297, Pearson's Chi-square test). Although fracture location was not significantly related to union rate (p = 0.584, Mann-Whitney test), patients with an effective working length of the distal segment of < 0.75 were prone to nonunion (p = 0.003, Pearson's Chi-square test). CONCLUSIONS: Although no significant difference was found in IM nail type, the IM nail with a shorter working length distal to the fracture showed a strong relationship with nonunion. PMID- 29799077 TI - Digoxin Use in Infants with Single Ventricle Physiology: Secondary Analysis of the Pediatric Heart Network Infant Single Ventricle Trial Public Use Dataset. AB - Digoxin has been associated with reduced interstage mortality after Norwood procedure. We sought to determine its association with survival and change in weight-for-age Z-score (WAZ) before the superior cavopulmonary connection (SCPC) surgery and at 14 months in a heterogeneous group of single ventricle infants. We performed a post-hoc analysis of the Pediatric Heart Network Infant Single Ventricle public use dataset to determine associations between digoxin and survival, transplant-free survival, and change in WAZ pre-SCPC and at 14 months. Sub-analyses of survival and transplant-free survival were performed for subjects who underwent Damus-Kaye-Stansel (DKS)/Norwood. Propensity score weighting was used in Cox hazard-proportion models. Of 229 subjects, 82 (36%) received digoxin and 147 (64%) received no digoxin. Pre-SCPC and 14-month survival and transplant free survival were not significantly different between the digoxin and no digoxin groups for the main cohort and DKS/Norwood sub-group. However, in DKS/Norwood subjects there was a trend towards improved interstage transplant-free survival in the digoxin group (95.7 vs. 89.6%, p = 0.08). Digoxin was associated with a greater decrease in WAZ from birth to pre-SCPC (- 1.96 +/- 0.19 vs. - 1.31 +/- 0.18, p < 0.001) and birth to 14 months (- 0.64 +/- 0.15 vs. - 0.19 +/- 0.15, p = 0.03). Digoxin was not associated with improved survival during the interstage or at 14 months in a mixed single ventricle cohort, but there was a trend towards improved interstage transplant-free survival in post-Norwood infants. As digoxin was associated with poorer weight gain, further research is needed to identify the risks/benefits for anatomic subtypes of infants with single ventricles. PMID- 29799079 TI - Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care. AB - Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting. PMID- 29799081 TI - Casein kinase 2 alpha and beta subunits inversely modulate ABA signal output in Arabidopsis protoplasts. AB - MAIN CONCLUSION: Our transient gene expression analyses in Arabidopsis protoplasts support the view that CK2alphas and CK2betas positively and negatively modulate ABRE-dependent gene expression, respectively. The phytohormone abscisic acid (ABA) regulates the expression of thousands of genes via ABA-responsive elements (ABREs), and has a crucial role in abiotic stress response. Casein kinase II (CK2), a conserved Ser/Thr protein kinase in eukaryotes, is essential for plant viability. Although the CK2 has been known as a tetrameric holoenzyme comprised of two catalytic alpha and two regulatory beta subunits, each of the two types of subunits has been proposed to have independent functions. The Arabidopsis genome encodes four alpha subunits (CK2alpha1, CK2alpha2, CK2alpha3, CK2alpha4) and four beta subunits (CK2beta1, CK2beta2, CK2beta3, CK2beta4). There is a growing body of evidence linking CK2 to ABA signaling and abiotic stress responses. However, the roles of each CK2 subunit in ABA signaling remain largely elusive. Using the transient expression system with the core ABA signaling components in Arabidopsis leaf mesophyll protoplasts, we show here that CK2alpha1 and CK2alpha2 (CK2alpha1/2) positively modulate ABRE dependent gene expression as ABA signal output in ABA signaling, whereas all four CK2betas negatively modulate the ABRE-dependent gene expression mediated by subclass III SnRK2-AREB/ABF pathway and by CK2alpha1/2. These data indicate that CK2alpha1/2 and CK2betas positively and negatively modulate ABA signal output, respectively, suggesting that the quantitative balance of CK2 subunits determines the ABA signal output in plants. Given that CK2s act as pleiotropic enzymes involved in multiple developmental and stress-responsive processes, our findings suggest that CK2 subunits may be involved in integration and coordination of ABA dependent and -independent signaling. PMID- 29799082 TI - Heterografting induced DNA methylation polymorphisms in Hevea brasiliensis. AB - MAIN CONCLUSION: Heterografting induced intraclonal epigenetic variations were detected among rubber plants. Interaction between genetically divergent root stock and scion tissues might have triggered these epigenetic changes which may eventually lead to intraclonal variability in rubber. DNA methylation in response to stress may be associated with the alteration in gene transcription leading to morphological changes in plants. Rubber tree is commercially propagated by bud grafting where the scion of a high yielding variety is grafted on to a genetically divergent root stock. Still, significant levels of intraclonal variations exist among them. Epigenetic changes associated with heterografting may be partly responsible for this conundrum. In the present study, an attempt was made to identify the impact of divergent root stock on the epigenome of scion in grafted rubber plants. Heterografts were developed by grafting eye buds from a single polyembryony derived seedling on to genetically divergent root stocks of unknown parentage. The plants were uniformly maintained and their DNA was subjected to MSAP analysis. Polymorphic DNA methylation bands corresponding to CG as well as the plant-specific CHG types of methylation were observed. Cloning of selected polymorphic regions and bisulfite sequencing confirmed the presence of methylation in the promoter and coding region of important genes including an LRR receptor kinase gene. Since divergent root stock is the major factor differentiating the grafted plants, the changes in DNA methylation patterns might have been triggered by the interaction between the two genetically different tissues of stock and scion. The study assumes importance in Hevea, because accumulation and maintenance of epigenetic changes in functional genes and promoters during subsequent cycles of vegetative propagation may contribute towards intraclonal variability eventually leading to altered phenotypes. PMID- 29799080 TI - The challenge of drug resistance in cancer treatment: a current overview. AB - It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested. PMID- 29799084 TI - Evaluation of a new slim lateral wall electrode for cochlear implantation: an imaging study in human temporal bones. AB - PURPOSE: To evaluate the insertion characteristics and trauma of a new slim lateral wall electrode (SlimJ) in human temporal bones (TB). METHODS: Pre- and postoperative assessment was performed using cone beam computed tomography (CBCT) and image fusion in 11 human TB. The position of the array in each cochlea was analyzed and described using a vertical scaling factor, calculated by dividing the distance of the scala tympani floor to the centre of the electrode by the duct height. Insertion trauma was scaled according to the presumed localization of the basilar membrane, which was modeled from histologic sections of 20 TBs. The insertion trauma was described by the adaptation of the Eshragi trauma grading. RESULTS: A full electrode insertion, via the round window, was achieved in all TBs. Surgical handling was good, with a favorable compromise between high flexibility but sufficient stiffness to facilitate smooth insertions. The median angular insertion depth was 368 degrees (range 330 degrees -430 degrees ). Scala tympani placement was achieved in ten out of eleven TBs; in one TB a scala translocation was observed, occurring at approximately 180 degrees . CONCLUSIONS: The SlimJ showed atraumatic insertion characteristics. The CBCT fusion technique provides an accurate and reliable assessment of the electrode position and allows for grading insertion trauma without histology. The SlimJ true potential for structure and hearing preservation needs to be further assessed in vivo. PMID- 29799083 TI - Provox 2(r) and Provox Vega(r) device life-time: a case-crossover study with multivariate analysis of possible influential factors and duration. AB - INTRODUCTION: Tracheoesophageal speech is considered the gold standard for rehabilitation following total laryngectomy. Current literature is limited and contradictory about the possible causes of device failure. The aim of the study is to compare the device life-time between the Provox 2 and Provox Vega and to examine possible related factors that influence their duration. METHODS: Retrospective case-crossover study in 34 laryngectomized patients who had undergone tracheoesophageal voice rehabilitation using indwelling Provox 2 and Provox Vega voice prostheses between 2010 and 2016 in a tertiary care centre. RESULTS: A total of 440 prostheses were evaluated. The most frequent reason for replacement was due to an endoprosthesis leakage (n = 221, 64.2%) in both models. Radiotherapy increases the risk of prosthesis replacement (IRR = 1.88, p = 0.007) as well as bilateral neck dissection (IRR = 1.56, p = 0.017) in Provox 2. Age and unilateral neck dissection do not seem to influence the duration of the prosthesis. Mean life-time of Provox 2 was 106.64 days and 124.19 days for Provox Vega (p = 0.261). Complementary treatment with radiotherapy demonstrated a lower device survival (p < 0.001). DISCUSSION: Results confirmed the non-significant differences on device life between Provox Vega and Provox 2, as well as the relevant role of radiotherapy treatment in the increase of replacements and diminution of the device duration. PMID- 29799085 TI - Venoarterial extracorporeal membrane oxygenation support for neonatal and pediatric refractory septic shock: more than 15 years of learning. AB - : The objective of the study was to report our institutional experience in the management of children and newborns with refractory septic shock who required venoarterial extracorporeal membrane oxygenation (VA ECMO) treatment, and to identify patient-and infection-related factors associated with mortality. This is a retrospective case series in an intensive care unit of a tertiary pediatric center. Inclusion criteria were patients <= 18 years old who underwent a VA ECMO due to a refractory septic shock due to circulatory collapse. Patient conditions and support immediately before ECMO, analytical and hemodynamic parameter evolution during ECMO, and post-canulation outcome data were collected. Twenty one patients were included, 13 of them (65%) male. Nine were pediatric and 12 were newborns. Median septic shock duration prior to ECMO was 29.5 h (IQR, 20 46). Eleven patients (52.4%) suffered cardiac arrest (CA). Neonatal patients had worse Sepsis Organ Failure Assessment (SOFA) score, Oxygenation Index and PaO2/FiO2 ratio, blood gas analysis, lactate levels, and left ventricular ejection fraction compared to pediatric patients. Survival was 33.3% among pediatric patients (60% if we exclude pneumococcal cases) and 50% among newborns. Hours of sepsis evolution and mean airway pressure (MAP) prior to ECMO were significantly higher in the non-survivor group. CA was not a predictor of mortality. Streptococcus pneumoniae infection was a mortality risk factor. There was an improvement in survival during the second period, from 14.3 to 57.2%, related to shorter sepsis evolution before ECMO placement, better candidate selection, and greater ECMO support once the patient was placed. CONCLUSION: Patients with refractory septic shock should be transferred precociously to a referral ECMO center. However, therapy should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis. What is Known: * Children with refractory septic shock have significant mortality rates, and although ECMO is recommended, overall survival is low. * There are no studies regarding characteristics of infections as predictors of pediatric survival in ECMO. What is New: * Septic children should be transferred precociously to referral ECMO centers during the first hours if patients do not respond to conventional therapy. * Treatment should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis. PMID- 29799086 TI - Risk factors for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a case-control study. AB - : The etiology and pathogenesis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome are unclear. We performed a case control study to evaluate potential environmental or lifestyle factors associated with PFAPA morbidity. We enrolled 119 patients with PFAPA syndrome who had undergone tonsillectomy in Oulu University Hospital between 1987 and 2007. We recruited 230 controls, matched for sex, birth date, and place from the database of the Population Register Center of Finland. All the patients and controls completed a questionnaire regarding exposure to environmental triggers during early childhood. Maternal smoking was more common among PFAPA syndrome patients than controls (23 vs. 14%; P = 0.005). PFAPA patients had lower breastfeeding rates than controls (94 vs. 99%; P = 0.006). No other environmental factors were associated with PFAPA syndrome, except having an aquarium at home (P = 0.007). The patient group also used natural or herbal medicines more often than the controls (P = 0.01). CONCLUSION: Maternal smoking and lack of breastfeeding, known risk factors for common childhood infections, were more common in patients with PFAPA syndrome than in matched controls. Environmental factors may be important in the pathogenesis of PFAPA syndrome and should be evaluated in future studies. What is Known: * The pathogenesis and genetics of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome remain unsolved. * PFAPA syndrome has been shown to cluster in families. What is New: * Maternal smoking and lack of breastfeeding are more common in patients with PFAPA syndrome than in the controls. * Environmental risk factors may be important in the pathogenesis of the syndrome. PMID- 29799088 TI - Comparative mitogenomics reveals large-scale gene rearrangements in the mitochondrial genome of two Pleurotus species. AB - In the present study, we assembled the mitogenomes of Pleurotus citrinopileatus and Pleurotus platypus. The circular mitogenome of the two Pleurotus species comprises a set of 14 conserved protein-encoding genes (PEGs), 2 RNA genes (small subunit ribosomal RNA and large subunit ribosomal RNA), and 24 tRNAs, with sizes of 60,694 and 73,807 bp, respectively. They contain 4 and 10 introns with 3 and 10 intronic open reading frames (ORFs), respectively. Thirteen position classes (Pcls) of introns were found in the cox1 gene of four Pleurotus species. The number and class of Pcl varied among different Pleurotus species, indicating that numerous events of loss and gain occurred during evolution of Pleurotus. Comparative mitogenomic and collinearity analyses reveal that large-scale gene rearrangements may have occurred during the evolution of Pleurotus citrinopileatus and Pleurotus platypus, including gene rearrangements and inversions, which may be related to the observed high amounts of repetitive DNA elements (5.62 and 5.45%, respectively). Phylogenetic analysis based on concatenated mitochondrial protein sequences reveals that concatenated mitochondrial genes are suitable as molecular markers for phylogenetic analysis. This serves as the first report on large-scale rearrangements in the mitochondria of the genus Pleurotus, thereby improving our understanding of the evolution of the Pleurotus genus and other macrofungi. PMID- 29799089 TI - Greener L-lactic acid production through in situ extractive fermentation by an acid-tolerant Lactobacillus strain. AB - Lactic acid (LA) fermentation requires a neutralizer for a physiologically acceptable range. However, a neutralizer generates a large amount of gypsum, an environmental pollutant. Furthermore, the downstream processing is complicated and expensive, comprising 50-70% of the total cost. We previously developed a Lactobacillus delbrueckii FM1, which can produce undissociated LA without neutralizer. Here, we improved FM1 by adaptive evolution at pH 4.5, which generated Adp FM1 showing an ~ 1.80-fold increase in LA production compared to FM1. The LA production via fed-batch fermentation yielded 36.2 g/L of LA, with a productivity of 0.500 g/L/h. However, cell viability was reduced due to the acidic pH and/or end-product inhibition. Therefore, an in situ LA recovery process using an extractive solvent was employed to maintain cell viability. Adp FM1 produced 49.2 g/L of LA via in situ LA-extractive fed-batch fermentation, which was ~ 1.4-fold higher than that without LA extraction. Adp FM1 provided a total LA productivity of 0.512 g/L/h in 96 h. Among the tested strains, Adp FM1 exhibited the highest H+-ATPase activity and a 415-fold increase in H+-ATPase gene expression compared to the parent strain. These results suggest that the in situ LA extractive fermentation process will ease downstream processing and prove to be a more economical and environmentally friendly option compared to the present fermentation. To our knowledge, this is the first report on the production of undissociated L-LA by Lactobacillus using an in situ recovery process, with high LA production levels and productivity. PMID- 29799087 TI - Comparative study of Salmonella enterica serovar Enteritidis genes expressed within avian and murine macrophages via selective capture of transcribed sequences (SCOTS). AB - Salmonella enterica serovar Enteritidis (SE) is a communicable zoonotic bacterium. Macrophages are essential for Salmonella survival, transmission, and infection. In this study, selective capture of transcribed sequences (SCOTS) was used to screen genes preferentially expressed by SE during contact with macrophages from different hosts. We found 57 predicted genes and 52 genes expressed by SE during interaction with avian HD-11 and murine RAW264.7 cells, respectively. These expressed genes were involved in virulence, metabolism, stress response, transport, regulation, and other functions. Although genes related to survival or metabolic pathways were needed during SE infection, different gene expression profiles of SE occurred in the two macrophage cell lines. qRT-PCR results confirmed that most screened genes were upregulated during infection in contrast to the observation during in vitro cultivation, with different expression levels in infected avian macrophages at 2-h and 7-h post infection. In addition, in vitro and in vivo competition assays confirmed that SEN3610 (a putative deoR family regulator) and rfaQ (related to LPS synthesis) were closely related to SE virulence in both mice and chickens. Three putative transcriptional regulators, SEN2967, SEN4299, and rtcR, were related to SE colonization in mice, while the ycaM mutation caused decreased infection and survival of SE in HD-11 cells without influencing virulence in mice or chicken. Genes showing differential expression between SE-infected avian and murine macrophages indicate specific pathogen adaptation to enable infection of various hosts. PMID- 29799090 TI - Carbon flux to growth or polyhydroxyalkanoate synthesis under microaerophilic conditions is affected by fatty acid chain-length in Pseudomonas putida LS46. AB - Economical production of medium-chain length polyhydroxyalkanoates (mcl-PHA) is dependent on efficient cultivation processes. This work describes growth and mcl PHA synthesis characteristics of Pseudomonas putida LS46 when grown on medium chain length fatty acids (octanoic acid) and lower-cost long-chain fatty acids (LCFAs, derived from hydrolyzed canola oil) in microaerophilic environments. Growth on octanoic acid ceased when the oxygen uptake rate was limited by the oxygen transfer rate, and mcl-PHA accumulated to 61.9% of the cell dry mass. From LCFAs, production of non-PHA cell mass continued at a rate of 0.36 g L-1 h-1 under oxygen-limited conditions, while mcl-PHA accumulated simultaneously to 31% of the cell dry mass. The titer of non-PHA cell mass from LCFAs at 14 h post inoculation was double that obtained from octanoic acid in bioreactors operated with identical feeding and aeration conditions. While the productivity for octanoic acid was higher by 14 h, prolonged cultivation on LCFAs achieved similar productivity but with twice the PHA titer. Simultaneous co-feeding of each substrate demonstrated the continued cell growth under microaerophilic conditions characteristic of LCFAs, and the resulting polymer was dominant in C8 monomers. Furthermore, co-feeding resulted in improved PHA titer and volumetric productivity compared to either substrate individually. These results suggest that LCFAs improve growth of P. putida in oxygen-limited environments and could reduce production costs since more non-PHA cell mass, the cellular factories required to produce mcl-PHA and the most oxygen-intensive cellular process, can be produced for a given oxygen transfer rate. PMID- 29799092 TI - How to never be wrong. AB - Human beliefs have remarkable robustness in the face of disconfirmation. This robustness is often explained as the product of heuristics or motivated reasoning. However, robustness can also arise from purely rational principles when the reasoner has recourse to ad hoc auxiliary hypotheses. Auxiliary hypotheses primarily function as the linking assumptions connecting different beliefs to one another and to observational data, but they can also function as a "protective belt" that explains away disconfirmation by absorbing some of the blame. The present article traces the role of auxiliary hypotheses from philosophy of science to Bayesian models of cognition and a host of behavioral phenomena, demonstrating their wide-ranging implications. PMID- 29799091 TI - Systemic Therapy of Lung Cancer CNS Metastases Using Molecularly Targeted Agents and Immune Checkpoint Inhibitors. AB - Central nervous system (CNS) metastases most commonly arise from lung cancer, with the majority of patients affected during their disease course. The prognosis for patients with untreated brain metastases is poor, with surgical resection and/or radiotherapy as classic therapeutic options. However, the value of systemic therapy in the management of CNS metastases from lung cancer is growing. Novel targeted agents for the treatment of non-small cell lung cancer (NSCLC) have demonstrated activity in treating patients with CNS involvement, and are potential alternatives to radiation and surgery. These agents include anaplastic lymphoma kinase (ALK) inhibitors such as alectinib, crizotinib, ceritinib, lorlatinib, and others; epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including the recently developed third-generation inhibitor osimertinib, and even immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab. This review summarizes current activity of systemic agents in the management of CNS metastases from NSCLC, as well as potential mechanisms of action of these small and large molecules. PMID- 29799093 TI - Self-face advantage over familiar and unfamiliar faces: A three-level meta analytic approach. AB - Despite the increasing number of researchers interested in self-face, so far, no study has summarized the behavioral findings that contribute to the debate on self-face advantage. Most studies have focused on neural correlates of the self, although functional uniqueness can also be considered an important criterion for determining whether a stimulus is unique. The present meta-analysis systematically compared reaction time (RT) responses for self-face with other face identities across 54 studies. Different moderator factors were tested: familiarity, identity, head angle, laterality, and culture. We used a three-level meta-analytic approach, which is the best approach to account for the dependency of effect sizes. Results showed a significant (Hedges's gav = -0.298) effect size, indicating faster RT for self-face than for other faces in general. Except for culture, none of the moderators employed significantly impacted on the main effect. Regarding culture, results showed that participants from Western cultures tend to respond faster to their own face than to other people's faces, while for participants from Eastern cultures, the effect was not significant. In summary, our results indicate that the self-face benefits from an advantage in terms of reaction time and may be considered a unique stimulus. Implications and limitations of the results are discussed. PMID- 29799095 TI - Grading of carotid artery stenosis with computed tomography angiography: whether to use the narrowest diameter or the cross-sectional area. AB - OBJECTIVES: To compare the estimation of carotid artery stenosis by computed tomography angiography (CTA) based on cross-sectional area versus the smallest diameter measurement, and test the accuracy of both CTA measurements using color Doppler ultrasonography (CDUS) as a reference method. METHODS: For 113 carotid arteries with stenosis >=50% we analysed the differences in the estimated stenosis level between both CTA methods and CDUS using the Bland-Altman approach. Further, we calculated sensitivity, specificity and plotted receiver operating characteristic (ROC) curves for both CTA methods. RESULTS: The mean difference between CDUS and CTA (area) measurements was -0.4% (p = 0.68); between CDUS and CTA (diameter), 20.7% (p < 0.001); and between CTA (area) and CTA (diameter), 21.2% (p < 0.001). Sensitivity and specificity for the CTA (area) method were 81% and 77%, and for CTA (diameter) were 23% and 100%. The area under the curve (AUC) for CTA (diameter) was 0.62 (0.57, 0.66), and for CTA (area) 0.79 (0.71-0.87). The equality test for the two AUCs was <0.0001. CONCLUSIONS: CTA (diameter)-based measurements significantly underestimated the degree of carotid stenosis. We recommend the CTA (area) method because of its higher predictive power for a correct stenosis classification and a lack of significant difference in the estimated stenosis level, compared to CDUS. MAIN MESSAGES: * Cross-sectional area measurement considers asymmetric shape of the residual vessel lumen. * CTA (diameter) method on average significantly underestimates the true level of stenosis. * CTA (area) method correctly classifies vessels needing surgical intervention. PMID- 29799096 TI - Avelumab: A Review in Metastatic Merkel Cell Carcinoma. AB - Avelumab (Bavencio(r)) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration >= 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naive in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis. PMID- 29799094 TI - Pacing Decision Making in Sport and the Effects of Interpersonal Competition: A Critical Review. AB - An athlete's pacing strategy is widely recognised as an essential determinant for performance during individual events. Previous research focussed on the importance of internal bodily state feedback, revealed optimal pacing strategies in time-trial exercise, and explored concepts such as teleoanticipation and template formation. Recently, human-environment interactions have additionally been emphasized as a crucial determinant for pacing, yet how they affect pacing is not well understood. Therefore, this literature review focussed on exploring one of the most important human-environment interactions in sport competitions: the interaction among competitors. The existing literature regarding the regulation of exercise intensity and the effect of competition on pacing and performance is critically reviewed in this paper. The PubMed, CINAHL and Web of Science electronic databases were searched for studies about pacing in sports and (interpersonal) competition between January 2000 to October 2017, using the following combination of terms: (1) Sports AND (2) Pacing, resulting in 75 included papers. The behaviour of opponents was shown to be an essential determinant in the regulation of exercise intensity, based on both observational (N = 59) and experimental (N = 16) studies. However, adjustment in the pacing response related to other competitors appears to depend on the competitive situation and the current internal state of the athlete. The findings of this review emphasize the importance of what is happening around the athlete for the outcome of the decision-making process involved in pacing, and highlight the necessity to incorporate human-environment interactions into models that attempt to explain the regulation of exercise intensity in sports and exercise. PMID- 29799098 TI - The correlation between the Aquatic Decomposition Score (ADS) and the post-mortem submersion interval measured in Accumulated Degree Days (ADD) in bodies recovered from fresh water. AB - The Aquatic Decomposition Score (ADS) made by van Daalen et al., was developed to approximate the Post-Mortem Submersion Interval (PMSI) in bodies recovered in salt water. Since the decomposition process in salt water differs from the process in fresh water due to salinity, the temperature, and the depth of the water, we wanted to investigate whether there is a correlation between the ADS and the PMSI and if the ADS can be used to make an estimation of the PMSI in bodies recovered from fresh water. For the latter, the PMSI was measured using Accumulated Degree Days (ADD). In our study we included seventy-six human remains found outdoors in fresh water. Their decomposition was measured using the ADS. A strong correlation was found between the ADS and the PMSI. Also, it was found that the ADS can significantly estimate the ADD. Despite the more varied circumstances under which bodies in fresh water are found when compared to those found in salt water, the ADS can be used to measure the decomposition and accurately estimate the ADD, and thus the PMSI. More research is needed to validate our method and make a prediction model with smaller confidence intervals. PMID- 29799097 TI - Cutaneous toxicities of new treatments for melanoma. AB - New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy. PMID- 29799099 TI - Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active Controlled, Multicentre, Phase II Trial. AB - BACKGROUND: Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. METHODS: A dose finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged >= 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. RESULTS: Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. CONCLUSION: Significant improvement in the benefit-risk ratio was observed for CTC (doses >= 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. FUNDING: Laboratorios del Dr. Esteve, S.A.U. PMID- 29799100 TI - No QTc Prolongation with Semaglutide: A Thorough QT Study in Healthy Subjects. AB - INTRODUCTION: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia. METHODS: In a parallel design, 168 healthy subjects were randomized to the treatment or placebo arms, of whom 166 were treated with subcutaneous semaglutide (N = 83; escalated to a supratherapeutic dose of 1.5 mg) or placebo (N = 83). The subjects (60% males) had a mean age of 38.2 years and body mass index of 25.1 kg/m2. To assess QT assay sensitivity, subjects in the placebo group received a single 400 mg moxifloxacin dose as positive control, and placebo in a crossover fashion. The primary endpoint was the time-matched change from baseline in QT interval corrected individually for heart rate (DeltaQTcI), calculated from 11 electrocardiogram recordings from 0 to 48 h after the last 1.5 mg dose. Similar assessments were made for the therapeutic 0.5 and 1.0 mg semaglutide dose levels. RESULTS: No QTcI prolongation occurred with any semaglutide dose; the upper limits of two-sided 90% confidence intervals of the placebo-subtracted DeltaQTcI were < 10 ms at all doses and time points. Exposure-response analysis showed no dependence of QTcI on semaglutide concentration. QT assay sensitivity was confirmed. The semaglutide safety profile was similar to that of other GLP-1 receptor agonists. CONCLUSION: Based on investigations of QT/QTc, no concern with regard to ventricular arrhythmias was raised as semaglutide did not prolong the cardiac repolarization duration in healthy subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 02064348. FUNDING: Novo Nordisk. PMID- 29799102 TI - Impact of Appointment Waiting Time on Attendance Rates at a Clinical Cancer Genetics Service. AB - The increase in demand for clinical cancer genetics services has impacted the ability to provide services timeously. Given limited resources, this often results in extended appointment waiting times. Over the last 3 years, the Cancer Genetics Service at the National Cancer Centre Singapore has continued to experience a steady increase in demand for its service. Nevertheless, significant no-show rates have been reported. This study sought to determine whether an association exists between appointment waiting times and attendance rates. Data was gathered for all participants meeting inclusion criteria. Attendance rates and appointment waiting times were calculated. The relationship between mean waiting times for those who did and did not attend their scheduled appointments was evaluated using Welch's t test and linear regression model. The results showed a significant difference in mean appointment waiting times between patients who did and did not attend (32.66 versus 43.50 days respectively; p < 0.0001). Furthermore, patients who waited for longer than 37 days were significantly less likely to attend. No-show rates increased as the waiting time increased, at a rate of 19.60% per 20 days and 21.40% per 30 days. In conclusion, appointment waiting time is a significant predictor for patient attendance. Strategies to ensure patients receive an appointment within the necessary timeframe at the desired setting are important to ensure that individuals at increased cancer risk attend their appointments in order to manage their cancer risks effectively. PMID- 29799103 TI - c.835-5T>G Variant in SMN1 Gene Causes Transcript Exclusion of Exon 7 and Spinal Muscular Atrophy. AB - Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder caused by survival motor neuron (SMN) protein deficiency leading the loss of motor neurons in the anterior horns of the spinal cord and brainstem. More than 95% of SMA patients are attributed to the homozygous deletion of survival motor neuron 1 (SMN1) gene, and approximately 5% are caused by compound heterozygous with a SMN1 deletion and a subtle mutation. Here, we identified a rare variant c.835-5T>G in intron 6 of SMN1 in a patient affected with type I SMA. We analyzed the functional consequences of this mutation on mRNA splicing in vitro. After transfecting pCI-SMN1, pCI-SMN2, and pCI-SMN1 c.835-5T>G minigenes into HEK293, Neuro-2a, and SHSY5Y cells, reverse transcription polymerase chain reaction (RT PCR) was performed to compare the splicing effects of these minigenes. Finally, we found that this mutation resulted in the skipping of exon 7 in SMN1, which confirmed the genetic diagnosis of SMA. PMID- 29799101 TI - Mesenchymal Stem Cells: Miraculous Healers or Dormant Killers? AB - Mesenchymal Stem Cells (MSCs) are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency to differentiate into mesodermal cell lineages. The use of MSCs in clinical settings began with high enthusiasm and the number of MSC-based clinical trials has been rising ever since. However; the very unique characteristics of MSCs that made them suitable to for therapeutic use, might give rise to unwanted outcomes, including tumor formation and progression. In this paper, we present a model of carcinogenesis initiated by MSCs, which chains together the tissue organization field theory, the stem cell theory, and the inflammation-cancer chain. We believe that some tissue resident stem cells could be leaked cells from bone marrow MSC pool to various injured tissue, which consequently transform and integrate in the host tissue. If the injury persists or chronic inflammation develops, as a consequence of recurring exposure to growth factors, cytokines, etc. the newly formed tissue from MSCs, which still has conserved their mesenchymal and stemness features, go through rapid population expansion, and nullify their tumor suppressor genes, and hence give rise to neoplastic cell (carcinomas, sarcomas, and carcino-sarcomas). Considering the probability of this hypothesis being true, the clinical and therapeutic use of MSCs should be with caution, and the recipients' long term follow-up seems to be insightful. PMID- 29799105 TI - The Effect of Spiritual Self-care Training on the Quality of Life of Mothers of Preterm Infants: A Randomized Controlled Trial. AB - The present study was carried out with the aim of determining the effect of spiritual self-care training on the quality of life of mothers of preterm infants. This trial was carried out on 60 mothers with premature infants. Mothers were randomly divided into two intervention and control groups. Training for increasing awareness about the condition of the infants was carried out in both groups. In the intervention group, spiritual self-care training was also done. Data were completed in both groups before, immediately after, and two weeks after the intervention by using the standard WHO quality of life questionnaire. Data were analysed using statistical tests, including ANOVA and Repeated Measures. The results showed that the average quality of life of mothers under study was significantly different at different points of measurement in the intervention group (first, second, and third time-points) (P = 0.016). An increase was observed in the intervention group at the second time-point compared to the first time-point (84.2-88.4, P < 0.001) and in the third time-point compared to the first time-point, (87.9), which was also statistically significant (P < 0.001). According to the results of post hoc tests, there was a decrease in quality of life in the control group at the second time-point compared to the first time point and the average score of mothers decreased from 82.9 to 75.3, which was statistically significant (P < 0.001). Spiritual self-care training can increase the quality of life and can be used as a form of holistic nursing care for mothers with premature infants in neonatal intensive care units. PMID- 29799104 TI - Hispidulin Protects Against Focal Cerebral Ischemia Reperfusion Injury in Rats. AB - Focal cerebral ischemia is associated with ischemia/reperfusion (I/R) injury. Hispidulin is a flavonoid compound with a variety of pharmacological properties. The neuroprotective effects of hispidulin have not been fully elucidated. Herein, we demonstrated that pretreatment of animals with hispidulin improved the neurological outcomes and decreased the infarct size and brain edema in the cerebral focal I/R model. Mechanistically, we showed in vivo and in vitro that hispidulin exerted a protective effect against I/R injury by inducing the Nrf2 antioxidant pathway through modulation of AMPK/GSK3beta signaling. Taken together, our results suggest that hispidulin may be a useful neuroprotective agent against ischemia/reperfusion (I/R) injury. PMID- 29799106 TI - Sleeve Gastrectomy with Ligamentum Teres Cardiopexy. PMID- 29799107 TI - Characterization of Self-Reported Dysphagia and Impact on Weight Outcomes After Laparoscopic Sleeve Gastrectomy. AB - INTRODUCTION/AIMS: There is paucity of literature examining dysphagia after laparoscopic sleeve gastrectomy (LSG). Moreover, there are few validated scoring systems for dysphagia that adequately assess its psychosocial impact. We aim to investigate dysphagia after LSG using a multidimensional scale that examines its functional and emotional impact. As secondary aims, we evaluated the impact of dysphagia on weight outcomes and its relationship with pre-operative gastro esophageal reflux disease (GERD) and proton pump inhibitor (PPI) use. METHODS: One hundred twenty-four patients 1 year or more post-LSG were administered the validated Dysphagia Handicap Index (DHI) questionnaire. To further delineate esophageal dysphagia, three additional questions were added. One hundred one patients (81.5%) responded. Physical, Emotional, Functional, and Esophageal scales were analyzed combined and individually using a multivariate model. RESULTS: No patients reported dysphagia pre-operatively. The median DHI scale scores are the following: Physical-2 (0-20); Functional-4 (0-22); Emotional-2 (0 14); and Esophageal-2 (0-8). On multivariate analysis, DHI Emotional scores significantly correlated with reduced total weight loss (%TWL) (p = 0.001) and excess weight loss (%EWL) (p = 0.023). The physical symptoms of dysphagia did not affect weight outcomes. Post-operatively, PPI usage increased significantly (15.8 vs 19.8%, p = 0.01) and correlated with higher dysphagia scores. CONCLUSION: A statistically validated dysphagia-specific questionnaire was utilized to evaluate the impact of LSG on dysphagia including its functional and emotional influences. The psychosocial handicap of dysphagia significantly reduced weight loss outcomes. A correlation between PPI use and dysphagia after LSG was found. The prevalence of dysphagia after LSG and the factors that contribute to its symptoms need to be further studied. PMID- 29799108 TI - The intelligent OR: design and validation of a context-aware surgical working environment. AB - PURPOSE: Interoperability of medical devices based on standards starts to establish in the operating room (OR). Devices share their data and control functionalities. Yet, the OR technology rarely implements cooperative, intelligent behavior, especially in terms of active cooperation with the OR team. Technical context-awareness will be an essential feature of the next generation of medical devices to address the increasing demands to clinicians in information seeking, decision making, and human-machine interaction in complex surgical working environments. METHODS: The paper describes the technical validation of an intelligent surgical working environment for endoscopic ear-nose-throat surgery. We briefly summarize the design of our framework for context-aware system's behavior in integrated OR and present example realizations of novel assistance functionalities. In a study on patient phantoms, twenty-four procedures were implemented in the proposed intelligent surgical working environment based on recordings of real interventions. Subsequently, the whole processing pipeline for context-awareness from workflow recognition to the final system's behavior is analyzed. RESULTS: Rule-based behavior that considers multiple perspectives on the procedure can partially compensate recognition errors. A considerable robustness could be achieved with a reasonable quality of the recognition. Overall, reliable reactive as well as proactive behavior of the surgical working environment can be implemented in the proposed environment. CONCLUSIONS: The obtained validation results indicate the suitability of the overall approach. The setup is a reliable starting point for a subsequent evaluation of the proposed context-aware assistance. The major challenge for future work will be to implement the complex approach in a cross-vendor setting. PMID- 29799109 TI - Correction to: Temperature and Pressure Dependences of the Elastic Properties of Tantalum Single Crystals Under <100> Tensile Loading: A Molecular Dynamics Study. AB - In the original publication of this article [1] the third author was typesetted by mistake. PMID- 29799110 TI - A case of normal pressure hydrocephalus presenting as ventriculoperitoneal shunt responsive dementia and choreodystonia. PMID- 29799111 TI - Decreasing Use of Percutaneous Endoscopic Gastrostomy Tube Feeding in Japan. AB - OBJECTIVES: To identify trends in percutaneous endoscopic gastrostomy (PEG) tube placement and intravenous hyperalimentation (IVH) in nonhospital settings (as a potential alternative to tube feeding for nutrition) and to summarize published reports concerning the decision-making process for PEG placement. DESIGN: National survey and systematic review. SETTING: Japan. PARTICIPANTS: All Japanese people. MEASUREMENTS: Data on numbers of individuals with a PEG tube and IVH were obtained from the website of the Japanese Ministry of Health, Labour, and Welfare and published reports concerning the decision-making process for PEG placement in Japan were summarized. RESULTS: The number of PEG tube placements peaked in 2007 and has been decreasing since Japan experienced the Great East Japan Earthquake in 2011. A further decline was seen in 2015 after the Japanese Ministry of Health, Labour and Welfare revised the fee schedule in 2014. More than half of individuals who had tubes were aged 80 and older during the years observed. In contrast, the number of individuals receiving IVH was lowest in the same year as PEG tube placement peaked and has been increasing ever since. Four studies reported that the decision-making process included consideration of not only the underlying disease, but also the individual's age and social barriers and the physician's personal philosophy. CONCLUSION: The number of PEG tube placements has been decreasing since its peak in 2007, and the number of individuals receiving IVH has been increasing. Many factors influence the decision-making process for PEG tube placement. Physicians in Japan may be realizing that there is little evidence to support the use of tube feeding in frail elderly adults. PMID- 29799112 TI - Efficacy and Tolerability of Direct-Acting Antivirals for Hepatitis C in Older Adults. AB - OBJECTIVES: To evaluate the efficacy and tolerability of direct-acting antiviral (DAA) therapy in individuals aged 65 and older. DESIGN: Retrospective review between June 2014 and January 2017. SETTING: Viral hepatitis outpatient clinic. PARTICIPANTS: Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25). MEASUREMENTS: Drug-drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed. RESULTS: Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02). CONCLUSION: DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin-induced anemia, during therapy. PMID- 29799113 TI - Changes in sleep quality and levels of psychological distress during the adaptation to university: The role of childhood adversity. AB - Stress-related sleep disturbances are common, and poor sleep quality can negatively affect health. Previous work indicates that early-life adversity is associated with compromised sleep quality later in life, but it is unknown whether it predicts greater declines in sleep quality during stressful life transitions. We propose and test a conceptual model whereby individuals who reported experiencing greater levels of child maltreatment would experience greater psychological distress during a stressful life transition, which in turn would contribute to greater declines in sleep quality, relative to their quality of sleep before the stressful transition. Controlling for potential confounding variables (e.g., age, gender), structural equation modelling demonstrated that psychological distress experienced during a stressful transition (i.e., beginning life at university) mediated the relationship between childhood emotional neglect and changes in sleep quality. The hypothesized model demonstrated a good overall fit to the data, chi 2 (15) = 17.69, p = .279, CFI = .99, TLI = .97, SRMR = .04, RMSEA = .04 (90% CI <0.001-0.09). Emotional neglect (beta = .22) was positively associated with psychological distress which in turn was positively associated with poor sleep quality (beta = .31) during a stressful transition. Future research should aim to understand the specific stressors in the university environment that are most challenging to individuals who faced early-life emotional maltreatment. These findings will help inform interventions to facilitate adaptation to a new environment and improve sleep quality for these university students. PMID- 29799114 TI - Applying the phenotype approach for rosacea to practice and research. AB - BACKGROUND: Rosacea diagnosis and classification have evolved since the 2002 National Rosacea Society expert panel subtype approach. Several working groups are now aligned to a more patient-centric phenotype approach, based on an individual's presenting signs and symptoms. However, subtyping is still commonplace across the field and an integrated strategy is required to ensure widespread progression to the phenotype approach. OBJECTIVES: To provide practical recommendations that facilitate adoption of a phenotype approach across the rosacea field. METHODS: A review of the literature and consolidation of rosacea expert experience. RESULTS: We identify challenges to implementing a phenotype approach in rosacea and offer practical recommendations to overcome them across clinical practice, interventional research, epidemiological research and basic science. CONCLUSIONS: These practical recommendations are intended to indicate the next steps in the progression from subtyping to a phenotype approach in rosacea, with the goals of improving our understanding of the disease, facilitating treatment developments and ultimately improving care for patients with rosacea. PMID- 29799115 TI - Monkey viral pathology in the Sukhum colony and modeling human viral infections. AB - The data characterizing spontaneous infections of Old World monkeys: measles, poliomyelitis, hepatitis A (HPA), encephalomyocarditis, coronavirus infection, simian hemorrhagic fever (SHF), are presented. The experimental infections were reproduced with the isolated pathogens. On these models, pathogenesis and epidemiology of these diseases were studied. The efficiency of poliomyelitis, measles and HPA vaccines is shown. The priority of data on the discovery of earlier unknown disease-SHF and "Sukhumi" virus-are emphasized. Several important pathogenic mechanisms common for various hemorrhagic fevers were studied on experimental SHF of macaques. This model is uniquely safe and adequate for the assessment of therapy of hemorrhagic fevers dangerous for humans. PMID- 29799118 TI - Is genetic drift to blame for testicular dysgenesis syndrome in Semliki chimpanzees (Pan troglodytes schweinfurthii)? AB - BACKGROUND: We present 3 likely cases of testicular dysgenesis syndrome (TDS) within a community of chimpanzees (Pan troglodytes schweinfurthii). We tested whether genetic drift may be the culprit, as a genetic cause has been suspected to account for TDS among other wildlife. METHODS: We successfully sequenced a 367 bp segment spanning the first hypervariable region within the D-loop of the mitochondrial genome for 78 DNA samples. RESULTS: We found 24 polymorphic sequence sites consisting of 7 singletons and 17 parsimony informative sites. This sample contained 9 haplotypes with a diversity index of 0.78 (SD = 0.03). All tests against the null hypothesis of neutral polymorphisms were non significant (P > .10). The mismatch distribution of pairwise differences does not fit a Poisson's curve (raggedness index = 0.166; SSD = 0.12; P = 1). CONCLUSIONS: Thus, we found no significant signs of genetic isolation, population expansion, or genetic bottleneck. Alternative causes of TDS and how they might pertain to this population are discussed. PMID- 29799117 TI - Effect of a Sodium Alginate Coating Infused with Tea Polyphenols on the Quality of Fresh Japanese Sea Bass (Lateolabrax japonicas) Fillets. AB - : Sodium alginate (SA) and tea polyphenols (TP) are natural preservatives commonly used in the food industry, including the production of fish products. The effect of SA coating infused with TP on the quality of fresh Japanese sea bass (Lateolabrax japonicas) fillets was evaluated over a 20-day period at 4 degrees C. SA (1.5%, w/v) or TP (0.5%, w/v) treatment alone, and the SA coating infused with TP (SA-TP) all reduced microbial counts, with the SA-TP providing the greatest effect. Fish fillet samples treated with SA-TP had significantly lower levels of total volatile basic nitrogen, lipid oxidation, and protein decomposition during the storage period, relative to the remaining treatments. The samples treated with SA-TP had the highest sensory quality rating as well. Collectively, sodium alginate coating infused with tea polyphenols may represent a promising treatment for preservation of Japanese sea bass fillets during cold storage. PRACTICAL APPLICATION: The sodium alginate-tea polyphenols composite coating has strong potential to be used as a new biopreservative for maintaining fish fillet quality. PMID- 29799119 TI - Implementing Attachment and Biobehavioral Catch-Up with birth parents: Rationale and case example. AB - Attachment and Biobehavioral Catch-Up (ABC) is an intervention designed for vulnerable children and their parents. This intervention enhances parental sensitivity and nurturance with the goal of promoting secure, organized attachments and strong self-regulatory capabilities among children. Here, we provide a brief rationale for the need for such interventions to be delivered to parent-child dyads in the child welfare system. Next, we review specific intervention targets of ABC. We include a case example of two birth parents and their daughter who became involved in Child Protective Services due to domestic violence. PMID- 29799116 TI - Evaluating predisposition and training in shaping the musician's brain: the need for a developmental perspective. AB - The study of music training as a model for structural plasticity has evolved significantly over the past 15 years. Neuroimaging studies have identified characteristic structural brain alterations in musicians compared to nonmusicians in school-age children and adults, using primarily cross-sectional designs. Despite this emerging evidence and advances in pediatric neuroimaging techniques, hardly any studies have examined brain development in early childhood (before age 8) in association with musical training, and longitudinal studies starting in infancy or preschool are particularly scarce. Consequently, it remains unclear whether the characteristic "musician brain" is solely the result of musical training, or whether certain predispositions may have an impact on its development. Moving toward a developmental perspective, the present review considers various factors that may contribute to early brain structure prior to the onset of formal musical training. This review introduces a model for potential neurobiological pathways leading to the characteristic "musician brain," which involves a developmental interaction between predisposition and its temporal dynamics, environmental experience, and training-induced plasticity. This perspective illuminates the importance of studying the brain structure associated with musical training through a developmental lens, and the need for longitudinal studies in early childhood to advance our understanding of music training-induced structural plasticity. PMID- 29799120 TI - Transition from post-capillary pulmonary hypertension to combined pre- and post capillary pulmonary hypertension in swine: a key role for endothelin. AB - KEY POINTS: Passive, isolated post-capillary pulmonary hypertension (PH) secondary to left heart disease may progress to combined pre- and post-capillary or 'active' PH This 'activation' of post-capillary PH significantly increases morbidity and mortality, and is still incompletely understood. In this study, pulmonary vein banding gradually produced post-capillary PH with structural and functional microvascular remodelling in swine. Ten weeks after banding, the pulmonary endothelin pathway was upregulated, likely contributing to pre capillary aspects in the initially isolated post-capillary PH. Inhibition of the endothelin pathway could potentially stop the progression of early stage post capillary PH. ABSTRACT: Passive, isolated post-capillary pulmonary hypertension (IpcPH) secondary to left heart disease may progress to combined pre- and post capillary or 'active' PH (CpcPH) characterized by chronic pulmonary vascular constriction and remodelling. The mechanisms underlying this 'activation' of passive pulmonary hypertension (PH) remain incompletely understood. Here we investigated the role of the vasoconstrictor endothelin-1 (ET) in the progression from IpcPH to CpcPH in a swine model for post-capillary PH. Swine underwent pulmonary vein banding (PVB; n = 7) or sham-surgery (Sham; n = 6) and were chronically instrumented 4 weeks later. Haemodynamics were assessed for 8 weeks, at rest and during exercise, before and after administration of the ET receptor antagonist tezosentan. After sacrifice, the pulmonary vasculature was investigated by histology, RT-qPCR and myograph experiments. Pulmonary arterial pressure and resistance increased significantly over time. mRNA expression of prepro-endothelin-1 and endothelin converting enzyme-1 in the lung was increased, while ETA expression was unchanged and ETB expression was downregulated. This was associated with increased plasma ET levels from week 10 onward and a more pronounced vasodilatation to in vivo administration of tezosentan at rest and during exercise. Myograph experiments showed decreased endothelium-dependent vasodilatation to Substance P and increased vasoconstriction to KCl in PVB swine consistent with increased muscularization observed with histology. Moreover, maximal vasoconstriction to ET was increased whereas ET sensitivity was decreased. In conclusion, PVB swine gradually developed PH with structural and functional vascular remodelling. From week 10 onward, the pulmonary ET pathway was upregulated, likely contributing to pre-capillary activation of the initially isolated post-capillary PH. Inhibition of the ET pathway could thus potentially provide a pharmacotherapeutic target for early stage post-capillary PH. PMID- 29799121 TI - Failure of bacterial screening to detect Staphylococcus aureus: the English experience of donor follow-up. AB - BACKGROUND AND OBJECTIVES: Between February 2011 and December 2016, over 1.6 million platelet units, 36% pooled platelets, underwent bacterial screening prior to issue. Contamination rates for apheresis and pooled platelets were 0.02% and 0.07%, respectively. Staphylococcus aureus accounted for 21 contaminations, including four pooled platelets, one confirmed transfusion-transmitted infection (TTI) and three 'near-miss' incidents detected on visual inspection which were negative on screening. We describe follow-up investigations of 16 donors for skin carriage of S. aureus and molecular characterisation of donor and pack isolates. MATERIALS AND METHODS: Units were screened by the BacT/ALERT 3D detection system. Contributing donors were interviewed and consent requested for skin and nasal swabbing. S. aureus isolates were referred for spa gene type and DNA macrorestriction profile to determine identity between carriage strains and packs. RESULTS: Donors of 10 apheresis and two pooled packs screen positive for S. aureus were confirmed as the source of contamination; seven had a history of skin conditions, predominantly eczema; 11 were nasal carriers. The 'near-miss' incidents were associated with apheresis donors, two donors harboured strains indistinguishable from the pack strain. The TTI was due to a screen-negative pooled unit, and a nasal isolate of one donor was indistinguishable from that in the unit. CONCLUSION: Staphylococcus aureus contamination is rare but potentially harmful in platelet units. Donor isolates showed almost universal correspondence in molecular type with pack isolates, thus confirming the source of contamination. The importance of visual inspection of packs prior to transfusion is underlined by the 'near-miss' incidents. PMID- 29799122 TI - Do values explain the low employment levels of Muslim women around the world? A within- and between-country analysis. AB - Using worldwide data from the World Values Survey (WVS) gathered in 2010-2014, we examine two distinct ways in which Islam may be associated with women's employment. We show that, within their countries, Muslim women are less likely to be employed than women of other religions. We also examine between-country differences and find that, net of education and family statuses, the employment levels of women living in countries that are 90-100 per cent Muslim are not significantly different than those living in countries that are only 0-20 per cent Muslim. Then we test a prevailing view: that Islam discourages gender egalitarian values, and that these values - held by women themselves or people around them - explain why Muslim women are less likely to be employed than women of other religions within their own countries. Despite the rich measures of values in the WVS and a large sample, we find no evidence that values explain any of the lower employment of Muslim women, mainly because values have little or no effect on women's employment. Thus, we conclude that most of the world's gap in employment between Muslim women and other women is within-country and is not explained by gender ideology. Future research should examine alternative hypotheses, including ethno-religious discrimination. PMID- 29799124 TI - Multiple vegetating plaques on a Cesarean section scar. PMID- 29799123 TI - Current and Future Technologies for Microbiological Decontamination of Cereal Grains. AB - Cereal grains are the most important staple foods for mankind worldwide. The constantly increasing annual production and yield is matched by demand for cereals, which is expected to increase drastically along with the global population growth. A critical food safety and quality issue is to minimize the microbiological contamination of grains as it affects cereals both quantitatively and qualitatively. Microorganisms present in cereals can affect the safety, quality, and functional properties of grains. Some molds have the potential to produce harmful mycotoxins and pose a serious health risk for consumers. Therefore, it is essential to reduce cereal grain contamination to the minimum to ensure safety both for human and animal consumption. Current production of cereals relies heavily on pesticides input, however, numerous harmful effects on human health and on the environment highlight the need for more sustainable pest management and agricultural methods. This review evaluates microbiological risks, as well as currently used and potential technologies for microbiological decontamination of cereal grains. PMID- 29799125 TI - Positive patch test reaction to carbamazepine after a very long delay. PMID- 29799127 TI - Assessment of skin lesions produced by focused, tunable, mid-infrared chalcogenide laser radiation. AB - BACKGROUND: Traditionally, fractional laser treatments are performed with focused laser sources operating at a fixed wavelength. Using a tunable laser in the mid infrared wavelength range, wavelength-dependent absorption properties on the ablation process and thermal damage formation were assessed with the goal to obtain customizable tissue ablations to provide guidance in finding optimized laser exposure parameters for clinical applications. METHODS: Laser tissue experiments were carried out on full thickness ex vivo human abdominal skin using a mid-infrared tunable chromium-doped zinc selenide/sulfide chalcogenide laser. The laser has two independent channels: a continuous wave (CW) output channel which covers a spectrum ranging from 2.4 MUm to 3.0 MUm with up to 9.2 W output power, and a pulsed output channel which ranges from 2.35 MUm to 2.95 MUm. The maximum pulse energy of the pulsed channel goes up to 2.8 mJ at 100 Hz to 1,000 Hz repetition rate with wavelength-dependent pulse durations of 4-7 ns. RESULTS: Total ablation depth, ablation efficiency, and coagulation zone thickness were highly correlated to wavelength, pulse width, and pulse energy. Using the same total radiant exposure at 2.85 MUm wavelength resulted in 10-times smaller coagulation zones and 5-times deeper ablation craters for one hundred 6 ns pulses compared to one 100 ms pulse. For a fixed pulse duration of 6 ns and a total radiant exposure of 2.25 kJ/cm2 the ablation depth increased with longer wavelengths. CONCLUSION: The tunable laser system provides a useful research tool to investigate specific laser parameters such as wavelength on lesion shape, ablation depth and thermal tissue damage. It also allows for customization of the characteristics of laser lesions and therefore facilitates the selection of suitable laser parameters for optimized fractional laser treatments. Lasers Surg. Med. 50:961-972, 2018.(c) 2018 Wiley Periodicals, Inc. PMID- 29799128 TI - When hydroquinone meets methoxy radical: Hydrogen abstraction reaction from the viewpoint of interacting quantum atoms. AB - Interacting Quantum Atoms methodology is used for a detailed analysis of hydrogen abstraction reaction from hydroquinone by methoxy radical. Two pathways are analyzed, which differ in the orientation of the reactants at the corresponding transition states. Although the discrepancy between the two barriers amounts to only 2 kJ/mol, which implies that the two pathways are of comparable probability, the extent of intra-atomic and inter-atomic energy changes differs considerably. We thus demonstrated that Interacting Quantum Atoms procedure can be applied to unravel distinct energy transfer routes in seemingly similar mechanisms. Identification of energy components with the greatest contribution to the variation of the overall energy (intra-atomic and inter-atomic terms that involve hydroquinone's oxygen and the carbon atom covalently bound to it, the transferring hydrogen and methoxy radical's oxygen), is performed using the Relative energy gradient method. Additionally, the Interacting Quantum Fragments approach shed light on the nature of dominant interactions among selected fragments: both Coulomb and exchange-correlation contributions are of comparable importance when considering interactions of the transferring hydrogen atom with all other atoms, whereas the exchange-correlation term dominates interaction between methoxy radical's methyl group and hydroquinone's aromatic ring. This study represents one of the first applications of Interacting Quantum Fragments approach on first order saddle points. (c) 2018 Wiley Periodicals, Inc. PMID- 29799129 TI - JPEN Journal Club 35. Selective Data Presentation. PMID- 29799126 TI - The combined influence of cognitions in adolescent depression: Biases of interpretation, self-evaluation, and memory. AB - OBJECTIVES: Depression is characterized by a range of systematic negative biases in thinking and information processing. These biases are believed to play a causal role in the aetiology and maintenance of depression, and it has been proposed that the combined effect of cognitive biases may have greater impact on depression than individual biases alone. Yet little is known about how these biases interact during adolescence when onset is most common. METHODS: In this study, adolescents were recruited from the community (n = 212) and from a Child And Adolescent Mental Health Service (n = 84). Participants completed measures of depressive symptoms, interpretation bias, self-evaluation, and recall memory. These included the Mood and Feelings Questionnaire, Ambiguous Scenarios Test for Depression in Adolescents, Self-Description Questionnaire, and an immediate recall task. The clinically referred sample also took part in a formal diagnostic interview. RESULTS: Individual cognitive biases were significantly intercorrelated and associated with depression severity. The combination of cognitive biases was a stronger predictor of depression severity than individual biases alone, predicting 60% of the variance in depression severity across all participants. There were two significant predictors, interpretation bias and negative self-evaluation; however, almost all of the variance was explained by negative self-evaluation. CONCLUSIONS: The findings support the interrelationship and additive effect of biases in explaining depression and suggest that understanding the way in which cognitive biases interact could be important in advancing methods of identification, early intervention, and treatment. PRACTITIONER POINTS: A combination of biases was a better predictor of depression symptom severity than individual biases. Interpretation and self-evaluation were better predictors of depression symptom severity than recall. Negative self evaluation was the strongest individual predictor of depression symptom severity. Negative self-evaluation was able to classify depressed from non-depressed adolescents. The cross-sectional design of the study precludes any conclusions about the potential causal role of these variables. Different tasks were used to assess different types of cognitive bias meaning that the possible linear operation along an information processing 'pathway' could not be examined. PMID- 29799130 TI - A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy. AB - OBJECTIVE: Inflammation is a well-known consequence of surgery. Although surgical debulking of tumor is beneficial to patients, the onset of inflammation in injured tissue may impede the success of adjuvant therapies. One marker for postoperative inflammation is IL-6, which is released as a consequence of surgical injuries. IL-6 is predictive of response to many cancer therapies, and it is linked to various molecular and cellular resistance mechanisms. The purpose of this study was to establish a murine model by which therapeutic responses to photodynamic therapy (PDT) can be studied in the context of surgical inflammation. MATERIALS AND METHODS: Murine models with AB12 mesothelioma tumors were treated with either surgical resection or sham surgery with tumor incision but no resection. The timing and extent of IL-6 release in the tumor and/or serum was measured using enzyme-linked immunosorbent assay (ELISA) and compared to that measured in the serum of 27 consecutive, prospectively enrolled patients with malignant pleural mesothelioma (MPM) who underwent macroscopic complete resection (MCR). RESULTS: MPM patients showed a significant increase in IL-6 at the time MCR was completed. Similarly, IL-6 increased in the tumor and serum of mice treated with surgical resections. However, investigations that combine resection with another therapy make it necessary to grow tumors for resection to a larger volume than those that receive secondary therapy alone. As the larger size may alter tumor biology independent of the effects of surgical injury, we assessed the tumor incision model. In this model, tumor levels of IL-6 significantly increased after tumor incision. CONCLUSION: The tumor incision model induces IL-6 release as is seen in the surgical setting, yet it avoids the limitations of surgical resection models. Potential mechanisms by which surgical induction of inflammation and IL-6 could alter the nature and efficacy of tumor response to PDT are reviewed. These include a wide spectrum of molecular and cellular mechanisms through which surgically-induced IL-6 could change the effectiveness of therapies that are combined with surgery. The tumor incision model can be employed for novel investigations of the effects of surgically-induced, acute inflammation on therapeutic response to PDT (or potentially other therapies). Lasers Surg. Med. 50:440-450, 2018. (c) 2018 Wiley Periodicals, Inc. PMID- 29799131 TI - Longitudinal reference ranges for serial measurements of myocardial performance index (MPI) by conventional and pulsed-wave tissue Doppler in monochorionic diamniotic twins at 17 to 26 weeks of gestation. AB - OBJECTIVE: To describe the longitudinal changes of fetal myocardial performance index (MPI) measured by conventional Doppler (MPI) and by pulsed-wave tissue Doppler (MPI') based on a prospective cohort of uncomplicated monochorionic diamniotic twin. METHOD: Single-center observational study. We measured MPI and MPI' in the right and left ventricles 3 times between 17 and 26 weeks of gestation. Second-degree fractional polynomials were built to obtain the best fitting curves in relation to gestational age (weeks) for each parameter. Gestational age-specific reference values were estimated by using two-level hierarchical models. RESULTS: Eighty-three uncomplicated monochorionic pregnancies were included in our study with a total of 249 observations. Fetal cardiac function was measured as MPI RV and LV, MPI' RV and LV at a mean gestational age of 18+3 (range 17+1 to 19+2 ), 22+3 (21+1 to 23+5 ), and 24+3 (22+6 to 26+2 ) weeks. The reference ranges for MPI LV, MPI RV, MPI' LV, and MPI' RV at 17 to 26 weeks were constructed and conditional percentiles calculated. CONCLUSION: The present study provides additional data on fetal cardiac function in uncomplicated monochorionic diamniotic twin gestations, describing the evolution of MPI and MPI' in both ventricles in uncomplicated monochorionic diamniotic pregnancies. PMID- 29799132 TI - Insights into geometries, stabilities, electronic structures, reactivity descriptors, and magnetic properties of bimetallic Nim Cun-m (m = 1, 2; n = 3-13) clusters: Comparison with pure copper clusters. AB - A long-range corrected density functional theory (LC-DFT) was applied to study the geometric structures, relative stabilities, electronic structures, reactivity descriptors and magnetic properties of the bimetallic NiCun-1 and Ni2 Cun-2 (n = 3-13) clusters, obtained by doping one or two Ni atoms to the lowest energy structures of Cun , followed by geometry optimizations. The optimized geometries revealed that the lowest energy structures of the NiCun-1 and Ni2 Cun-2 clusters favor the Ni atom(s) situated at the most highly coordinated position of the host copper clusters. The averaged binding energy, the fragmentation energies and the second-order energy differences signified that the Ni doped clusters can continue to gain an energy during the growth process. The electronic structures revealed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies of the LC-DFT are reliable and can be used to predict the vertical ionization potential and the vertical electron affinity of the systems. The reactivity descriptors such as the chemical potential, chemical hardness and electrophilic power, and the reactivity principle such as the minimum polarizability principle are operative for characterizing and rationalizing the electronic structures of these clusters. Moreover, doping of Ni atoms into the copper clusters carry most of the total spin magnetic moment. (c) 2018 Wiley Periodicals, Inc. PMID- 29799133 TI - Open-tubular capillary electrochromatographic determination of ten sulfonamides in tap water and milk by a metal-organic framework-coated capillary column. AB - In this study, a metal-organic framework (MOF), [Mn(cam)(bpy)], was synthesized and characterized by thermogravimetric analysis, scanning electron microscopy, and Fourier transform infrared spectrometry. An open-tubular capillary column was fabricated from [Mn(cam)(bpy)] via the amide coupling method. Ten types of sulfonamides were separated through the fabricated capillary column, which showed a good limits of detection (<0.07 MUg/mL) and linear ranges (1-100 or 5-100 MUg/mL) with a high correlation coefficients (R2 > 0.9987). The intra-day, inter day and column-to-column relative standard deviations (RSDs) in the migration times ranged from 0.44 to 4.87%, and the peak area RSDs ranged from 0.80 to 7.28%. The developed capillary electrochromatography method can be successfully utilized for the determination of sulfonamides in tap water and milk samples. PMID- 29799134 TI - OCT-based angiography of human dermal microvascular reactions to local stimuli: Implications for increasing capillary blood collection volumes. AB - OBJECTIVES: To measure and compare microvascular responses within the skin of the upper arm to local stimuli, such as heating or rubbing, through the use of optical coherence tomography angiography (OCTA), and to investigate its impact on blood volume collection. MATERIALS AND METHODS: With the use of heat packs or rubbing, local stimulation was applied to the skin of either the left or right upper arm. Data from the stimulated sites were obtained using OCTA comparing pre- and post-stimulation microvascular parameters, such as vessel density, mean vessel diameter, and mean avascular pore size. Additionally, blood was collected using a newly designed collection device and volume was recorded to evaluate the effect of the skin stimulation. RESULTS: Nineteen subjects were recruited for local stimulation study (including rubbing and heating) and 21 subjects for blood drawn study. Of these subjects, 14 agreed to participate in both studies. OCTA was successful in monitoring and measuring minute changes in the microvasculature of the stimulated skin. Compared to baseline, significant changes after local heating and rubbing were respectively found in vessel density (16% [P = 0.0004] and 33% [P < 0.0001] increase), mean vessel diameter (14% and 11% increase) and mean avascular pore size (5% [P = 0.0068] and 8% [P = 0.0005] decrease) after stimulations. A gradual recovery was recorded for each parameter, with no difference being measured after 30 minutes. Blood collection volumes significantly increased after stimulations of heating (48% increase; P = 0.049) and rubbing (78% increase; P = 0.048). Significant correlations were found between blood volume and microvascular parameters except mean avascular pore size under the heating condition. CONCLUSIONS: OCTA can provide important information regarding microvascular adaptations to local stimuli. With that, both heating and rubbing of the skin have positive effects on blood collection capacity, with rubbing having the most significant effect. Lasers Surg. Med. 50:908-916, 2018. (c) 2018 Wiley Periodicals, Inc. PMID- 29799136 TI - Nitrogen Balance During Venovenous Extracorporeal Membrane Oxygenation Support: Preliminary Results of a Prospective, Observational Study. AB - BACKGROUND: Current literature is insufficient to support specific guidelines for estimating nutrition needs during extracorporeal membrane oxygenation (ECMO). The purpose of this single-center observational study was to investigate protein catabolism during venovenous (VV) ECMO support and assess whether current nutrition recommendations were adequate. METHODS: All patients admitted to the Lung Rescue Unit between November 2016 and June 2017 were screened for eligibility. Patients with a documented nitrogen balance (NB) study were included in the data set. NB results were excluded for a change in blood urea nitrogen >=10 mg/dL during the urine collection or unquantified nitrogen losses. Demographics, ECMO-specific data, NB, nutrition prescription, and infusion were recorded in a prospective, observational manner. RESULTS: After exclusions, 25 NB results in 16 patients were included for analysis. Nonobese (body mass index [BMI] ? 30 kg/m2 ) and obese (BMI >= 30 kg/m2 ) patients received 85% and 84% of their prescribed protein, respectively. Nonobese patients had a mean NB of -1.7 +/- 5.7, whereas obese patients had a mean NB of -11.5 +/- 9.6. Obese patients displayed significantly higher urine urea nitrogen (26.7 +/- 7.7 vs 13.5 +/- 4.3; P = .00004). CONCLUSIONS: These preliminary findings suggest that current guidelines for estimating protein needs in critically ill patients may be adequate for nonobese patients receiving VV ECMO. However, current protein recommendations for critically ill obese patients may not be adequate during VV ECMO support, possibly related to significantly higher rates of catabolism. Future studies with a larger cohort of patients are needed to confirm these results. PMID- 29799137 TI - Cerebral edema induced by laser interstitial thermal therapy and radiotherapy in close succession in patients with brain tumor. AB - OBJECTIVE: Laser interstitial thermal therapy (LITT) is an image-guided technique that uses high temperature to ablate pathological tissue. Brain tumor patients undergoing LITT may also undergo radiation therapy (RT) either before or after LITT. Both procedures have been reported to increase cerebral edema and thereby the two treatments in close succession may worsen existing edema that can be difficult to control. The purpose of our study was to determine the frequency of increased and/or symptomatic cerebral edema after combined LITT and RT, the radiographic and clinical signs of this cerebral edema, and the treatment required. MATERIALS AND METHODS: This is a single center, retrospective study of patients who underwent LITT and RT less than 60 days apart. Brain Magnetic Resonance Imaging (MRI) and clinical information were reviewed at three time points (pre-treatment, post-LITT, and post-RT). RESULTS: The study cohort comprised eight patients: six with glioblastoma, one with anaplastic astrocytoma, and one with metastasis. Pre-treatment MRI showed cerebral edema in seven patients. Post-LITT MRI showed worsening cerebral edema in three patients, of which one was symptomatic. Post-RT MRI showed worsening cerebral edema in one patient. One patient who received RT before LITT had asymptomatic cerebral edema post-RT that improved post-LITT. Three patients required prolonged steroid therapy (>65 days), while two patients required bevacizumab for steroid refractory edema. CONCLUSIONS: LITT and RT treatment in close succession can induce cerebral edema, which can usually be managed successfully with steroids, although the treatment period may be prolonged. A minority of patients may require more aggressive treatment, such as bevacizumab. Lasers Surg. Med. 50:917 923, 2018. (c) 2018 Wiley Periodicals, Inc. PMID- 29799135 TI - A Standardized Telephone Intervention Algorithm Improves the Survival of Ventricular Assist Device Outpatients. AB - Ventricular assist devices (VADs) are an established therapeutic option for patients with chronic heart failure. Continuous monitoring of VAD parameters and their adherence to guidelines are crucial to detect problems in an early stage to optimize outcomes. A telephone intervention algorithm for VAD outpatients was developed, clinically implemented and evaluated. During the phone calls, a structured inquiry of pump parameters, alarms, blood pressure, INR, body weight and temperature, exit-site status and heart failure symptoms was performed and electronically categorized by an algorithm into 5 levels of severity. VAD outpatient outcomes without (n = 71) and with bi-weekly telephone interviews in their usual care (n = 25) were conducted using proportional hazard Cox regression, with risk adjustment based on a propensity score model computed from demographics and risk factors. From February 2015 through October 2017, 25 patients (n = 3 HeartMate II, n = 4 HeartMate 3 and n = 18 HeartWare HVAD) underwent 637 telephone interventions. In 57.5% of the calls no problems were identified, 3.9% were recalled on the next day because of alarms. In 26.5% (n = 169), the VAD Coordinator had to refer to the physician due to elevated blood pressure (n = 125, >85 mm Hg), INR < 2.0 or > 4.0 (n = 24) or edema (n = 10), 11.9% of the calls led to a follow-up because of equipment or exit-site problems. Propensity-adjusted 2-year survival (89% vs. 57%, P = 0.027) was significantly higher for the telephone intervention group. Continuous, standardized communication with VAD outpatients is important for early detection of upcoming problems and leads to significantly improved survival. PMID- 29799138 TI - A new multivariate zero-adjusted Poisson model with applications to biomedicine. AB - Recently, although advances were made on modeling multivariate count data, existing models really has several limitations: (i) The multivariate Poisson log normal model (Aitchison and Ho, ) cannot be used to fit multivariate count data with excess zero-vectors; (ii) The multivariate zero-inflated Poisson (ZIP) distribution (Li et al., 1999) cannot be used to model zero-truncated/deflated count data and it is difficult to apply to high-dimensional cases; (iii) The Type I multivariate zero-adjusted Poisson (ZAP) distribution (Tian et al., 2017) could only model multivariate count data with a special correlation structure for random components that are all positive or negative. In this paper, we first introduce a new multivariate ZAP distribution, based on a multivariate Poisson distribution, which allows the correlations between components with a more flexible dependency structure, that is some of the correlation coefficients could be positive while others could be negative. We then develop its important distributional properties, and provide efficient statistical inference methods for multivariate ZAP model with or without covariates. Two real data examples in biomedicine are used to illustrate the proposed methods. PMID- 29799140 TI - Enantioselective Total Synthesis of Blennolide H and Phomopsis-H76 A and Determination of Their Structure. AB - This work reports on the enantioselective total synthesis of the two dimeric natural chromanone lactones phomopsis-H76 A (5) and blennolide H (6). Both syntheses could be achieved from chromane 11, which was obtained by an enantioselective Wacker-type cyclization with >99 % ee. The dimerization of the corresponding monomers was performed using a palladium-catalyzed Suzuki reaction. Moreover, within this work it was possible to revise the absolute configuration of phomopsis-H76 A and determine the relative as well as absolute configuration of blennolide H. PMID- 29799139 TI - Rhabdomyosarcoma and rhabdomyoma associated with nevoid basal cell carcinoma syndrome: Local treatment strategy. AB - This article presents the case of a child presenting with a rhabdomyosarcoma associated with a fetal rhabdomyoma in the setting of nevoid basal cell carcinoma syndrome. Oncologic strategy is discussed. PMID- 29799141 TI - A novel mutation in the DYSF gene in a patient with a presumed inflammatory myopathy. AB - Dysferlinopathy, a progressive muscular dystrophy, results from mutations in the Dysferlin gene (DYSF, MIM*603009). Traditional diagnosis relies on the reduction or absence of dysferlin. However, altered dysferlin has been observed in other myopathies, leading to a precise diagnosis through molecular genetics. In this study, we report a patient who was previously misdiagnosed as inflammatory myopathy based on routine clinicopathological examinations alone. However, muscle biopsy specimens were analyzed further by immunohistochemistry of muscular dystrophy-related proteins, and gene-targeted next generation sequencing (NGS) was used to correctly identify muscular dystrophy. DNA was sequenced with NGS and the detected mutation was verified by Sanger sequencing. Our targeted NGS found a novel missense mutation (c.5392G > A) in the DYSF gene, allowing correct diagnosis of LGMD2B in our patient. We discovered of a novel missense mutation in the DYSF gene and have broadened the DYSF mutation spectrum, which may be correlated in patients with presumed dysferlinopathy, especially when lymphocytic infiltration is observed. PMID- 29799142 TI - Different perspectives on the key challenges facing rural health: The challenges of power and knowledge. AB - OBJECTIVE: To examine the effects of dominant knowledge in rural health, including how they shape issues central to rural health. In particular, this article examines the roles of: (i) deficit knowledge of rural health workforce; (ii) dominant portrayals of generalism; and (iii) perceptions of inferiority about rural communities in maintaining health disparities between rural- and metropolitan-based Australians. DESIGN: A Foucauldian framework is applied to literature, evidence, case studies and key messages in rural health. Three scenarios are used to provide practical examples of specific knowledge that is prioritised or marginalised. RESULTS: The analysis of three areas in rural health identifies how deficit knowledge is privileged despite it undermining the purpose of rural health. First, deficit knowledge highlights the workforce shortage rather than the type of work in rural practice or the oversupply of workforce in metropolitan areas. Second, the construction of generalist practice as less skilled and more monotonous undermines other knowledge that it is diverse and challenging. Third, dominant negative stereotypes of rural communities discourage rural careers and highlight undesirable aspects of rural practice. CONCLUSION: The privileging of deficit knowledge pertaining to rural health workforce, broader dominant discourses of generalism and the nature of rural Australian communities reproduces many of the key challenges in rural health today, including persisting health disparities between rural- and metropolitan-based Australians. To disrupt the operations of power that highlight deficit knowledge and undermine other knowledge, we need to change the way in which rural health is currently constructed and understood. PMID- 29799144 TI - The ability of prior urinary cultures results to predict future culture results in neurogenic bladder patients. AB - AIMS: To determine if previous urinary cultures can predict the organism and susceptibility of subsequent urinary cultures in patients with neurogenic bladder dysfunction. METHODS: We retrospectively identified a sample of neurogenic bladder patients from a tertiary care urology clinic (July 2015-July 2016). We reviewed the patient chart, and then used the electronic laboratory record to identify all urine cultures done in the 2 years prior. We identified sequential culture pairs and determined the concordance of the initial culture organism to the subsequent one and similarly the concordance of the initial culture's antibiotic resistance status to the subsequent culture's one. RESULTS: We identified 146 people with neurogenic bladder (mostly due to spinal cord injury [n = 61], multiple sclerosis [n = 26], or spina bifida [n = 25]). These individuals used primarily intermittent catheterization (n = 69, 47%) spontaneous voiding (n = 59, 40%), or indwelling foley catheter (n = 31, 21%). During the previous 2-years, 81 participants had at least two positive urine cultures and a total of 479 cultures could be examined for organism/susceptibility concordance. There was 56% concordance of bacterial species between subsequent urine cultures, and this decreased significantly with increasing time between cultures (P = 0.02). Antibiotic susceptibility concordance was high for ciprofloxacin (77%), nitrofurantoin (79%), and trimethoprim-sulfamethoxazole (75%), with no significant change with increasing time between cultures (P > 0.90). CONCLUSIONS: Previous positive urine cultures can provide valuable information regarding future organism and antibiotic susceptibility in individuals with neurogenic bladder. The practise of reviewing the previous urine culture when selecting empiric therapy is likely an effective practise in this population. PMID- 29799143 TI - Superelastic Multimaterial Electronic and Photonic Fibers and Devices via Thermal Drawing. AB - Electronic and photonic fiber devices that can sustain large elastic deformation are becoming key components in a variety of fields ranging from healthcare to robotics and wearable devices. The fabrication of highly elastic and functional fibers remains however challenging, which is limiting their technological developments. Simple and scalable fiber-processing techniques to continuously codraw different materials within a polymeric structure constitute an ideal platform to realize functional fibers and devices. Despite decades of research however, elastomeric materials with the proper rheological attributes for multimaterial fiber processing cannot be identified. Here, the thermal drawing of hundreds-of-meters long multimaterial optical and electronic fibers and devices that can sustain up to 500% elastic deformation is demonstrated. From a rheological and microstructure analysis, thermoplastic elastomers that can be thermally drawn at high viscosities (above 103 Pa s), allowing the encapsulation of a variety of microstructured, soft, and rigid materials are identified. Using this scalable approach, fiber devices combining high performance, extreme elasticity, and unprecedented functionalities, allowing novel applications in smart textiles, robotics, or medical implants, are demonstrated. PMID- 29799145 TI - Work settings of the first seven cohorts of James Cook University Bachelor of Medicine, Bachelor of Surgery graduates: Meeting a social accountability mandate through contribution to the public sector and Indigenous health services. AB - OBJECTIVE: The James Cook University medical school's mission is to produce a workforce appropriate for the health needs of northern Australia. DESIGN, SETTING AND PARTICIPANTS: James Cook University medical graduate data were obtained via cross-sectional survey of 180 early-career James Cook University medical graduates from 2005-2011 (response rate of 180/298 contactable graduates = 60%). Australian medical practitioner data for 2005-2009 graduates were obtained via the 2015 'Medicine in Australia: Balancing Employment and Life' wave 8 dataset. MAIN OUTCOME MEASURE: Comparison of the range of work settings and hours worked by James Cook University medical graduates to Australian medical graduates. RESULTS: Compared to a similar group of Australian medical graduates, James Cook University Bachelor of Medicine, Bachelor of Surgery graduates are significantly more likely to work in government-funded 'public' organisations (hospitals, community health centres, Aboriginal Community Controlled Health Services, government departments, agencies or defence forces). In particular, James Cook University medical graduates were more likely to work in Aboriginal Community Controlled Health Services and community health centres and other state-run primary health care organisations than other Australian medical graduates. CONCLUSION: James Cook University medical graduates appear to work in a higher proportion of public settings; in particular, primary care settings, than Australian medical graduates. This is an appropriate mix for the predominantly rural and remote geography of Queensland and its associated medical workforce priorities. Reporting medical graduate outcomes by their nature of practice could be an important adjunct to other measures, such as geographic location and choice of specialty. PMID- 29799146 TI - Robert R. Myers: In Memoriam (April 15, 1946-April 19, 2018). PMID- 29799147 TI - Immune modulating therapy: An effective add-on intervention for psychosis of anti N-methyl-d-aspartate receptor encephalitis in Taiwan. PMID- 29799148 TI - Melatonin for preventing primary headache: A systematic review. AB - BACKGROUND: The aim of this study was to assess the effectiveness and safety of melatonin for primary headache. METHODS: This systematic review following the Cochrane Handbook for Systematic Reviews of Interventions recommendations and PRISMA Statement. RESULTS: Four randomized controlled trials were included (351 participants). According to the GRADE approach the quality of evidence was very low. The use of melatonin for migraine showed that (i) reduced the number of days with pain and the analgesic consumption when compared with placebo, (ii) no benefits on headache intensity, number of headache days and analgesics consumption when compared with amitriptyline, (iii) reduced the number of analgesic consumption, the attack frequency and the headache intensity when associated with propranolol plus nortriptyline vs placebo plus propranolol plus nortriptyline, and (iv) no difference for any of the interest outcomes when associated with propranolol plus nortriptyline vs sodium valproate plus propranolol plus nortriptyline. The use of melatonin for cluster headache when compared with placebo showed a reduction in the daily number of analgesic consumption and no difference in the number of daily attacks. Adverse events were poorly reported by all of the studies. CONCLUSION: This review found that so far there are few clinical trials, with poor methodological quality about melatonin for primary headaches. The available evidence is not sufficient to support the use of melatonin in clinical practice for this population. Further research is still necessary for assess its effects (benefits and harms) for primary headaches patients. Number of Protocol registration in PROSPERO database: CRD42017067105 (available at https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017067105) . PMID- 29799149 TI - Physical functioning and psychological morbidity among regional and rural cancer survivors: A report from a regional cancer centre. AB - OBJECTIVE: To identify factors associated with psychosocial, physical and practical difficulties of daily living and distress among cancer survivors from a regional area in Australia. DESIGN: Cross-sectional study. SETTING: Riverina region of southern New South Wales. PARTICIPANTS: The sample included 134 patients who completed treatment for breast, colorectal, lung or cancer at the Riverina Cancer Care Centre. MAIN OUTCOME MEASURES: Distress was assessed by the Distress Thermometer. Psychosocial, physical and practical difficulties of daily living were assessed by the Patient-Reported Outcomes Measurement Information System questionnaires. RESULTS: A high proportion of cancer survivors had abnormal scores for physical function, sleep disturbance, satisfaction with role, fatigue and pain interference, with many also displaying abnormal scores for anxiety, depression and distress. Survivors living in rural areas and those who had undergone surgery had higher odds of having abnormal scores for sleep disturbance than their counterparts. Living without a partner increased the odds of anxiety and depression. Having advanced disease increased the odds of anxiety and pain. Colorectal cancer and higher education were associated with depression. CONCLUSION: Monitoring for abnormal physical and psychosocial issues after cancer treatment is essential to maintain or improve psychosocial well-being during survivorship. When developing survivorship care plans for patients residing in regional centres, health professionals should consider availability of high quality and accessible support services in regional areas of Australia. PMID- 29799150 TI - Action of antimicrobial peptides and their prodrugs on model and biological membranes. AB - Antimicrobial peptides (AMPs) are promising broad-spectrum antibiotic candidates in the wake of multi-drug resistant pathogens. Their clinical use still requires a solution based on lead optimisation and/or formulation to overcome certain limitations, such as unwanted cytotoxicity. A prodrug approach could overcome this safety barrier and can be achieved through reversible reduction or neutralisation of the AMPs' net cationic charge. By prodrug activation through pathogen associated enzymes, this approach could increase the therapeutic index of membrane active peptides. P18, a cecropin/magainin hybrid, and WMR, a myxinidin analogue from hagfish, were used as templates for the design strategy. The membrane permeabilizing activities of these AMPs and their prodrugs are reported here for liposomes of either Escherichia coli polar lipid extract or a human model lipid system of phosphatidylcholine and cholesterol. These results are compared with their antibacterial and haemolytic activities. Overall, correlation between liposome permeabilization and the corresponding bioactivity is observed and indicate that the broad-spectrum antibacterial effect exerted by these peptides is associated with membrane disruption. Furthermore, the prodrug modification had a general negative influence on membrane disruption and bioactivity, notably as much on bacterial as on human membranes. This prodrug strategy is particularly successful when complete neutralisation of the AMP's net charge occurs. Thus, on-target selectivity between bacterial and human membranes can be improved, which may be used to prevent the unnecessary exposure of host cells and commensal bacteria to active AMPs. PMID- 29799151 TI - Experimental Evidence for Azeotrope Formation from Protic Ionic Liquids. AB - Herein, we present experimental evidence that protic ionic liquids (PILs), derived from 1 : 1 liquid mixtures of the organic superbases 1,5 diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with carboxylic acids, form azeotropic mixtures with acid/base molar fractions different from 1 : 1. The ability of the carboxylic acids to form strong hydrogen bonds with the PIL ion pair leads to an azeotropic composition richer in the acid component. The results show that the azeotropic composition is ruled by the extent of acid-base equilibrium and the relative volatility of the neutral species in the PIL medium. The PILs show marked negative deviations from Raoult's Law with the stronger superbase (DBU) leading to an azeotropic composition closer to the equimolar 1 : 1 ratio. PMID- 29799152 TI - LncRNA ABHD11-AS1 promotes the development of endometrial carcinoma by targeting cyclin D1. AB - To investigate the expression, role and mechanism of action of long non-coding RNA (lncRNA) ABHD11-AS1 in endometrial carcinoma. The expression of lncRNA ABHD11 AS1 was quantified by qRT-PCR in human endometrial carcinoma (n = 89) and normal endometrial tissues (n = 27). LncRNA ABHD11-AS1 was stably overexpressed or knocked-down in endometrial carcinoma cell lines to examine the cellular phenotype and expression of related molecules. Compared to normal endometrial tissue, lncRNA ABHD11-AS1 was significantly overexpressed in endometrial carcinoma. Overexpression of lncRNA ABHD11-AS1 promoted the proliferation, G1-S progression, invasion and migration of endometrial cancer cells; inhibited apoptosis; up-regulated cyclin D1, CDK1, CDK2, CDK4, Bcl-xl and VEGFA; and down regulated p16, while ABHD11-AS1 down-regulation has the opposite effect. RNA pull down demonstrated that lncRNA ABHD11-AS1 binds directly to cyclin D1. Knockdown of cyclin D1 can reverse the effect of ABHD11-AS1. Overexpression of lncRNA ABHD11-AS1 increased the tumorigenicity and up-regulated cyclin D1 in an in vivo model of endometrial cancer in nude mice. LncRNA ABHD11-AS1 functions as an oncogene to promote cell proliferation and invasion in endometrial carcinoma by positively targeting cyclin D1. PMID- 29799153 TI - Evaluating the implementation of a quality improvement process in General Practice using a realist evaluation framework. AB - RATIONALE, AIMS, AND OBJECTIVES: Underuse of anticoagulants in atrial fibrillation is known to increase the risk of stroke and is an international problem. The National Institute for Health Care and Excellence guidance CG180 seeks to reduce atrial fibrillation related strokes through prescriptions of Non vitamin K antagonist Oral Anticoagulants. A quality improvement programme was established by the West of England Academic Health Science Network (West of England AHSN) to implement this guidance into General Practice. A realist evaluation identified whether the quality improvement programme worked, determining how and in what circumstances. METHODS: Six General Practices in 1 region, became the case study sites. Quality improvement team, doctor, and pharmacist meetings within each of the General Practices were recorded at 3 stages: initial planning, review, and final. Additionally, 15 interviews conducted with the practice leads explored experiences of the quality improvement process. Observation and interview data were analysed and compared against the initial programme theory. RESULTS: The quality improvement resources available were used variably, with the training being valued by all. The initial programme theories were refined. In particular, local workload pressures and individual General Practitioner experiences and pre-conceived ideas were acknowledged. Where key motivators were in place, such as prior experience, the programme achieved optimal outcomes and secured a lasting quality improvement legacy. CONCLUSION: The employment of a quality improvement programme can deliver practice change and improvement legacy outcomes when particular mechanisms are employed and in contexts where there is a commitment to improve service. PMID- 29799154 TI - What is the guidelines challenge? The CauseHealth perspective. AB - This paper is an introduction to the conference, The Guidelines Challenge, held in Oxford in October 2017. My aim is to explain our motivation for organising this conference, as part of the research project Causation, Complexity, and Evidence in Health Sciences (CauseHealth). Depending on the professional starting point, the guidelines challenge can be interpreted in a number of ways. Our idea with this conference was to discuss guidelines from 3 overarching perspectives: practice, policy, and philosophy. In particular, we wanted to discuss some of the challenges that face anyone developing and implementing clinical guidelines in the evidence-based era of medicine. This introduction gives a brief overview of what CauseHealth sees as the guidelines challenge from these perspectives. More attention is given to the philosophical issues with which the CauseHealth project is particularly concerned, although a proper treatment or discussion of these issues naturally falls outside the scope of this introduction. PMID- 29799155 TI - Listeria, Then and Now: A Call to Reevaluate Patient Teaching Based on Analysis of US Federal Databases, 1998-2016. AB - INTRODUCTION: Listeria monocytogenes is a foodborne pathogen capable of crossing the placental-fetal barrier; infection with the bacterium causes listeriosis. An exposed fetus may suffer blindness, neurological damage including meningitis, or even death. The adverse consequences of listeriosis place the infection on the federally reportable disease list. Primary prevention relies on women avoiding 6 categories of foods most likely to be contaminated with L monocytogenes, as indicated in guidelines developed by the Centers for Disease Control and Prevention (CDC), adapted by the American College of Obstetricians and Gynecologists (ACOG) in 2014, and reaffirmed without changes by ACOG in 2016. This report contains a critical evaluation of United States listeriosis prevention guidelines. METHODS: Between 1998 and 2016, there were 876 identified listeriosis events documented in the illness and recall databases maintained by the CDC, Food and Drug Administration (FDA), and United States Department of Agriculture - Food Safety and Inspection Service (USDA-FSIS). Each contaminated food was manually compared to the existing listeriosis avoidance guidelines, placing each event within or outside the guidelines. Trends were analyzed over time. RESULTS: Database analysis demonstrates that prior to the year 2000, abiding by the current guidelines would have prevented all reported listeriosis cases. However, in 2015 and 2016, only 5% of confirmed L monocytogenes infections originated from the 6 food groups listed in the CDC and ACOG guidelines. Similar trends emerged for food processing plant recalls (USDA-FSIS database) and grocery store recalls (FDA database). The total number of listeriosis illnesses in the United States doubled from 2007 to 2014. DISCUSSION: A gradual shift in detection of L monocytogenes contamination in ready-to-eat meals, frozen foods, and ready to-eat salads has occurred. Another emerging culprit is pasteurized dairy products. Revision of listeriosis avoidance guidelines by a consensus-seeking, multidisciplinary task force, is needed. PMID- 29799158 TI - Osmium Tag for Post-transcriptionally Modified RNA. AB - 5-Methylcytidine (m5 C) and 5-methyluridine (m5 U) are highly abundant post transcriptionally modified nucleotides that are observed in various natural RNAs. Such nucleotides were labeled through a chemical approach, as both underwent oxidation at the C5=C6 double bond, leading to the formation of osmium-bipyridine complexes, which could be identified by mass spectrometry. This osmium tag made it possible to distinguished m5 C and m5 U from their isomers, 2'-O methylcytidine and 2'-O-methyluridine, respectively. Queuosine and 2-methylthio N6 -isopentenyladenosine in tRNA were also tagged through complex formation. PMID- 29799156 TI - Symbiont-mediated competition: Xenorhabdus bovienii confer an advantage to their nematode host Steinernema affine by killing competitor Steinernema feltiae. AB - Bacterial symbionts can affect several biotic interactions of their hosts, including their competition with other species. Nematodes in the genus Steinernema utilize Xenorhabdus bacterial symbionts for insect host killing and nutritional bioconversion. Here, we establish that the Xenorhabdus bovienii bacterial symbiont (Xb-Sa-78) of Steinernema affine nematodes can impact competition between S. affine and S. feltiae by a novel mechanism, directly attacking its nematode competitor. Through co-injection and natural infection assays we demonstrate the causal role of Xb-Sa-78 in the superiority of S. affine over S. feltiae nematodes during competition. Survival assays revealed that Xb-Sa 78 bacteria kill reproductive life stages of S. feltiae. Microscopy and timed infection assays indicate that Xb-Sa-78 bacteria colonize S. feltiae nematode intestines, which alters morphology of the intestine. These data suggest that Xb Sa-78 may be an intestinal pathogen of the non-native S. feltiae nematode, although it is a nonharmful colonizer of the native nematode host, S. affine. Screening additional X. bovienii isolates revealed that intestinal infection and killing of S. feltiae is conserved among isolates from nematodes closely related to S. affine, although the underlying killing mechanisms may vary. Together, these data demonstrate that bacterial symbionts can modulate competition between their hosts, and reinforce specificity in mutualistic interactions. PMID- 29799159 TI - Microcystic macular oedema in optic neuropathy: case series and literature review. AB - Cavitations in the inner nuclear layer associated with severe optic atrophy and loss of retinal ganglion cells have clinically been termed microcystic macular oedema (MME). We describe a case series of MME in patients of all ages but predominantly younger patients with a wide range of optic atrophies ranging from acute onset optic disc drusen associated ischemic optic neuropathy to slowly progressive disease as glaucoma. There were no physical distinctions between MME in different causes of optic atrophy suggesting a common causative mechanism. We reviewed the literature on MME and it appears that MME is associated with more severe visual loss, and is more common in hereditary optic neuropathies and neuromyelitis optica spectrum disease rather than in patients with optic atrophy secondary to multiple sclerosis and glaucoma. Three main causative mechanisms have been proposed, including increased vitreal traction on the macular as the ganglion cells are lost. Others have suggested that trans-synaptic loss of cells in the inner nuclear layer causes formation of empty spaces or cavities. Finally, some have hypothesized a disturbance in the fluid homeostasis of the inner retina as Muller cells are lost or their function is impaired. There are no known treatments of MME. In conclusion, MME seems to be a marker of severe optic nerve atrophy irrespective of the underlying cause. PMID- 29799157 TI - Aldehyde dehydrogenase 2 activation ameliorates CCl4 -induced chronic liver fibrosis in mice by up-regulating Nrf2/HO-1 antioxidant pathway. AB - Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is critical in the pathogenesis of alcoholic liver cirrhosis. However, the effect of ALHD2 on liver fibrosis remains to be further elucidated. This study aimed to demonstrate whether ALDH2 regulates carbon tetrachloride (CCl4 )-induced liver fibrosis and to investigate the efficacy of Alda-1, a specific activator of ALDH2, on attenuating liver fibrosis. ALDH2 expression was increased after chronic CCl4 exposure. ALDH2 deficiency accentuated CCl4 -induced liver fibrosis in mice, accompanied by increased expression of collagen 1alpha1, alpha-SMA and TIMP-1. Moreover, ALDH2 knockout triggered more ROS generation, hepatocyte apoptosis and impaired mitophagy after CCl4 treatment. In cultured HSC-T6 cells, ALDH2 knockdown by transfecting with lentivirus vector increased ROS generation and alpha-SMA expression in an in vitro hepatocyte fibrosis model using TGF-beta1. ALDH2 overexpression by lentivirus or activation by Alda-1 administration partly reversed the effect of TGF-beta1, whereas ALDH2 knockdown totally blocked the protective effect of Alda 1. Furthermore, Alda-1 administration protected against liver fibrosis in vivo, which might be mediated through up-regulation of Nrf2/HO-1 cascade and activation of Parkin-related mitophagy. These findings indicate that ALDH2 deficiency aggravated CCl4 -induced hepatic fibrosis through ROS overproduction, increased apoptosis and mitochondrial damage, whereas ALDH2 activation through Alda-1 administration alleviated hepatic fibrosis partly through activation of the Nrf2/HO-1 antioxidant pathway and Parkin-related mitophagy, which indicate ALDH2 as a promising anti-fibrotic target and Alda-1 as a potential therapeutic agent in treating CCl4 -induced liver fibrosis. PMID- 29799162 TI - MAP2K2 mutation as a cause of cardio-facio-cutaneous syndrome in an infant with a severe and fatal course of the disease. AB - Cardio-facio-cutaneous syndrome (CFCS), a rare congenital disorder of RASopathies, displays high phenotypic variability. Complications during pregnancy and in the perinatal period are commonly reported. Polyhydramnios is observed in over half of pregnancies and might occur with fetal macrocephaly, macrosomia, and/or heart defects. Premature birth is not uncommon and any complications like respiratory insufficiency, edema, and feeding difficulties are present and might delay accurate clinical diagnosis. Besides neonatal complications, CFCS newborns and later infants have distinctive dysmorphic features usually accompanied by neurological (hypotonia with motor delay, neurocognitive delay) findings. Also, heart defects usually present at birth. Herein, we present the case of a female baby born prematurely from a pregnancy complicated with polyhydramnios, presenting at birth with craniofacial features typical for RASopathies, heart defects, neurological abnormalities, and hyperkeratosis unusual for a neonatal period. Due to the presence of a heart defect and other complications related to premature birth, the course of the disease was severe with a fatal outcome at the age of 9 months. The RASopathy, particularly CFCS, clinical diagnosis was confirmed and de novo p.Phe57Ile mutation in MAP2K2 was identified. PMID- 29799160 TI - Oxymatrine exerts protective effects on osteoarthritis via modulating chondrocyte homoeostasis and suppressing osteoclastogenesis. AB - Osteoarthritis (OA) is a common degenerative disease characterized by the progressive destruction both articular cartilage and the subchondral bone. The agents that can effectively suppress chondrocyte degradation and subchondral bone loss are crucial for the prevention and treatment of OA. Oxymatrine (OMT) is a natural compound with anti-inflammatory and antitumour properties. We found that OMT exhibited a strong inhibitory effect on LPS-induced chondrocyte inflammation and catabolism. To further support our results, fresh human cartilage explants were treated with LPS to establish an ex vivo degradation model, and the results revealed that OMT inhibited the catabolic events of LPS-stimulated human cartilage and substantially attenuated the degradation of articular cartilage ex vivo. As subchondral bone remodelling is involved in OA progression, and osteoclasts are a unique cell type in bone resorption, we investigated the effects of OMT on osteoclastogenesis, and the results demonstrated that OMT suppresses RANKL-induced osteoclastogenesis by suppressing the RANKL-induced NFATc1 and c-fos signalling pathway in vitro. Further, we found that the anti inflammatory and anti-osteoclastic effects of oxymatrine are mediated via the inhibition of the NF-kappaB and MAPK pathways. In animal studies, OMT suppressed the ACLT-induced cartilage degradation, and TUNEL assays further confirmed the protective effect of OMT on chondrocyte apoptosis. MicroCT analysis revealed that OMT had an attenuating effect on ACLT-induced subchondral bone loss in vivo. Taken together, these results show that OMT interferes with the vicious cycle associated with OA and may be a potential therapeutic agent for abnormal subchondral bone loss and cartilage degradation in osteoarthritis. PMID- 29799163 TI - Fabrication of polymer-modified magnetic nanoparticle based adsorbents for the capture and release of quinolones by manipulating the metal-coordination interaction. AB - Functional polymers with a metal-coordination interaction have been fabricated for sample pretreatment. Poly(N-4-vinyl-benzyl iminodiacetic acid-co-methacrylic acid-co-styrene)-modified magnetic nanoparticles were prepared and used as solid phase extraction adsorbents for the analysis of quinolones by tuning the metal coordination interaction. In the construction of the polymer-based adsorbents, functional monomer (N-(4-vinyl)-benzyl iminodiacetic acid) and comonomers (methacrylic acid and styrene) were fabricated onto the magnetic nanoparticles by free radical polymerization. Factors affecting the performance of the adsorbents were investigated, and the results revealed that Fe3+ played a vital role in the formation of metal-coordination adsorbents. Compared with other compounds, the resultant adsorbents displayed good selectivity to quinolones due to the metal coordination complex (N-4-vinyl-benzyl iminodiacetic acid-Fe3+ -quinolones). Interestingly, the captured quinolones could be rapidly released by manipulating the metal-coordination interaction with Cu2+ . The linearity range for analysis of the test quinolones was 0.025-2.0 MUg/mL (R2 > 0.999), and the recovery varied from 80.0 to 100.7%. Further, the proposed adsorbents were combined with high-performance liquid chromatography for the analysis of quinolones in real urine samples. The results demonstrated that the prepared adsorbents have good selectivity and sensitivity for quinolones, showing great potential for drug analysis in real samples. PMID- 29799164 TI - Elemental sulfur reduction in the deep-sea vent thermophile, Thermovibrio ammonificans. AB - The reduction of elemental sulfur is an important energy-conserving pathway in prokaryotes inhabiting geothermal environments, where sulfur respiration contributes to sulfur biogeochemical cycling. Despite this, the pathways through which elemental sulfur is reduced to hydrogen sulfide remain unclear in most microorganisms. We integrated growth experiments using Thermovibrio ammonificans, a deep-sea vent thermophile that conserves energy from the oxidation of hydrogen and reduction of both nitrate and elemental sulfur, with comparative transcriptomic and proteomic approaches, coupled with scanning electron microscopy. Our results revealed that two members of the FAD-dependent pyridine nucleotide disulfide reductase family, similar to sulfide-quinone reductase and to NADH-dependent sulfur reductase (NSR), respectively, are over-expressed during sulfur respiration. Scanning electron micrographs and sulfur sequestration experiments indicated that direct access of T. ammonificans to sulfur particles strongly promoted growth. The sulfur metabolism of T. ammonificans appears to require abiotic transition from bulk elemental sulfur to polysulfide to nanoparticulate sulfur at an acidic pH, coupled to biological hydrogen oxidation. A coupled biotic-abiotic mechanism for sulfur respiration is put forward, mediated by an NSR-like protein as the terminal reductase. PMID- 29799161 TI - Emerging role of exosome signalling in maintaining cancer stem cell dynamic equilibrium. AB - Cancer stem cells (CSCs) are a small subset of heterogeneous cells existed in tumour tissues or cancer cell lines with self-renewal and differentiation potentials. CSCs were considered to be responsible for the failure of conventional therapy and tumour recurrence. However, CSCs are not a static cell population, CSCs and non-CSCs are maintained in dynamic interconversion state by their self-differentiation and dedifferentiation. Therefore, targeting CSCs for cancer therapy is still not enough,exploring the mechanism of dynamic interconversion between CSCs and non-CSCs and blocking the interconversion seems to be imperative. Exosomes are 30-100 nm size in diameter extracellular vesicles (EVs) secreted by multiple living cells into the extracellular space. They contain cell-state-specific bioactive materials, including DNA, mRNA, ncRNA, proteins, lipids, etc. with their specific surface markers, such as, CD63, CD81, Alix, Tsg101, etc. Exosomes have been considered as information carriers in cell communication between cancer cells and non-cancer cells, which affect gene expressions and cellular signalling pathways of recipient cells by delivering their contents. Now that exosomes acted as information carriers, whether they played role in maintaining dynamic equilibrium state between CSCs and non-CSCs and their mechanism of activity are unknown. This review summarized the current research advance of exosomes' role in maintaining CSC dynamic interconversion state and their possible mechanism of action, which will provide a better understanding the contribution of exosomes to dedifferentiation and stemness acquisition of non-CSCs, and highlight that exosomes might be taken as the attractive target approaches for cancer therapeutics. PMID- 29799165 TI - Cross-resistance to diflufenican and picolinafen and its inheritance in oriental mustard (Sisymbrium orientale L.). AB - BACKGROUND: An oriental mustard population (P40) was identified as resistant to diflufenican by screening at the field rate. As diflufenican and picolinafen both target phytoene desaturase (PDS), cross-resistance to picolinafen was suspected. The mechanism of resistance and its inheritance to diflufenican and picolinafen were investigated. RESULTS: At the lethal dose (LD50 ) level, population P40 was 237-fold more resistant to diflufenican and seven-fold more resistant to picolinafen compared to two susceptible populations. Population P40 also had a significantly higher resistance to diflufenican (237-fold) than a previously described P3 population (143-fold). In addition to the Leu-498-Val mutation in PDS identified in all individuals of the P3 and P40 populations, a Glu-425-Asp mutation was also found in P40. Neither mutation was detected in any individuals of the susceptible population. As the segregation of phenotype and genotype of the F2 individuals fitted the model for a single dominant allele, resistance to both diflufenican and picolinafen is likely encoded on the nuclear genome and is dominant. CONCLUSION: Resistance to diflufenican and picolinafen in the P40 population is likely conferred by Leu-498-Val and Glu-425-Asp mutations in the PDS gene. Inheritance of resistance to these herbicides is managed by a single dominant gene. (c) 2018 Society of Chemical Industry. PMID- 29799166 TI - Adhesion of gram-negative rod-shaped bacteria on 1D nano-ripple glass pattern in weak magnetic fields. AB - This research project has major applications in the healthcare and biomedical industries. Bacteria reside in human bodies and play an integral role in the mechanism of life. However, their excessive growth or the invasion of similar agents can be dangerous and may cause fatal or incurable diseases. On the other hand, increased exposure to electromagnetic radiation and its impact on health and safety is a common concern to medical science. Some nanostructure materials have interesting properties regarding facilitating or impeding cell growth. An understanding of these phenomena can be utilized to establish the optimum benefit of these structures in healthcare and medical research. We focus on the commonly found rod-shaped, gram-negative bacteria and their orientation and community development on the cellular level in the presence of weak magnetic fields on one dimensional nano-ripple glass patterns to investigate the impact of nanostructures on the growth pattern of bacteria. The change in bacterial behavior on nanostructures and the impact of magnetic fields will open up new venues in the utilization of nanostructures. It is noticed that bacterial entrapment in nano-grooves leads to the growth of larger colonies on the nanostructures, whereas magnetic fields reduce the size of colonies and suppress their growth. PMID- 29799167 TI - Professor Gustav Victor Rudolph Born (29 July 1921 - 16 April 2018). PMID- 29799168 TI - Morphological Abnormalities in True Bugs (Heteroptera) near Swiss Nuclear Power Stations. AB - After the nuclear accidents of Chernobyl and Fukushima, several studies reported adverse health effects on wildlife animals. Epidemiological studies in humans found significant increases of leukemia rates in young children residing within 5 km from nuclear power plants. This study investigates morphological abnormalities in true bugs (Heteroptera), collected in the environs of three Swiss nuclear power stations (NPS). The objective of the study is to test whether there is an increased frequency of abnormalities in the vicinity of NPS. We found a frequency of abnormalities of 14.1% at distances r < 5 km and a frequency of 6.8% for distances r > 5 km, a rate ratio of 2.1 (P < 0.0001). The corresponding odds ratio was 2.26 (95% CI: 1.59, 3.18). We also conducted logistic regression of abnormality rates on reciprocal distance for each NPS site. The trend was significant for NPS Beznau (regression coefficient beta = 1.5 +/- 0.3, P < 0.0001) but not significant for NPS Gosgen und NPS Leibstadt with little samples within 5 km. To the best of our knowledge, this study is the first to find adverse health effects on insects near operating nuclear power plants. Due to its ecological design, however, it cannot answer the question whether the effect is caused by radiation from nuclear power plants. PMID- 29799169 TI - Initial experience with robotic pancreatic surgery in Singapore: single institution experience with 30 consecutive cases. AB - BACKGROUND: Presently, the worldwide experience with robotic pancreatic surgery (RPS) is increasing although widespread adoption remains limited. In this study, we report our initial experience with RPS. METHODS: This is a retrospective review of a single institution prospective database of 72 consecutive robotic hepatopancreatobiliary surgeries performed between 2013 and 2017. Of these, 30 patients who underwent RPS were included in this study of which 25 were performed by a single surgeon. RESULTS: The most common procedure was robotic distal pancreatectomy (RDP) which was performed in 20 patients. This included eight subtotal pancreatectomies, two extended pancreatecto-splenectomies (en bloc gastric resection) and 10 spleen-saving-RDP. Splenic preservation was successful in 10/11 attempted spleen-saving-RDP. Eight patients underwent pancreaticoduodenectomies (five hybrid with open reconstruction), one patient underwent a modified Puestow procedure and one enucleation of uncinate tumour. Four patients had extended resections including two RDP with gastric resection and two pancreaticoduodenectomies with vascular resection. There was one (3.3%) open conversion and seven (23.3%) major (>Grade II) morbidities. Overall, there were four (13.3%) clinically significant (Grade B) pancreatic fistulas of which three required percutaneous drainage. These occurred after three RDP and one robotic enucleation. There was one reoperation for port-site hernia and no 30 day/in-hospital mortalities. The median post-operative stay was 6.5 (range: 3-36) days and there were six (20%) 30-day readmissions. CONCLUSION: Our initial experience showed that RPS can be adopted safely with a low open conversion rate for a wide variety of procedures including pancreaticoduodenectomy. PMID- 29799170 TI - Finite element analysis of the influence of three-joint spinal complex on the change of the intervertebral disc bulge and height. AB - This study evaluated the changes of height and bulging occurring in individual layers of the annulus fibrosus of the intervertebral disc for 3 load scenarios (axial compression, flexion, and extension). The numerical model of a single motion segment of the thoracic spine was analysed for 2 different configurations, ie, for the model of a physiological segment and a segment with the posterior column removed. In the physiological segment, all annulus fibrosus layers decrease in height regardless of the applied load, bulging outside the intervertebral disc. Removal of the posterior column increases mobility and disrupts the load transfer system, with the lamellae bulging into the intervertebral disc. PMID- 29799171 TI - Nitrospina bacteria in a rocky intertidal habitat (Quintay Bay, central Chile). AB - Nitrospina bacteria are among the most important nitrite oxidizers in coastal and open-ocean environments, but the relevance of the genus contrasts with the scarceness of information on their ecophysiology and habitat range. Thus far, Nitrospina bacteria have been the only nitrite oxidizers detected at high abundance in Chilean coastal waters. These levels are often higher than at other latitudes. In this study, the abundance of 16S-rRNA gene transcripts of Nitrospina (hereafter just transcripts) was measured by reverse transcription quantitative PCR in a rocky intertidal gradient and compared with the nearshore counterpart off central Chile (~33 degrees S). Rocky pond transcripts were also compared with the taxonomic composition of the macrobiota and bacterioplankton (by 16S-rRNA gene-based T-RFLP) in the intertidal gradient. Transcripts increased from warmer, saltier, and low-nitrite ponds in the upper intertidal zone (19.5 +/ 1.6 degrees C, 39.0 +/- 1.0 psu, 0.98 +/- 0.17 MUmol/L) toward cooler, less salty, and high-nitrite ponds (17.8 +/- 2.6 degrees C, 37.7 +/- 0.82 psu, 1.23 +/ 0.21 MUmol/L) from middle and low zones. These varied from ~1,000 up to 62,800 transcripts. This increasing trend in the number of transcripts toward the lower zone was positively associated with the Shannon's diversity index for the macrobiota (r = .81, p < .01). Moreover, an important increase in the average number of transcripts was observed in ponds with a greater number of fish in the upper (7,846 transcripts during 2013) and lower zones (62,800 transcripts during 2015). Altogether, intertidal and nearshore transcripts were significantly correlated with nitrite concentrations (r = .804, p ? .01); rocky pond transcripts outnumbered nearshore ones by almost two orders of magnitude. In summary, rocky ponds favored both the presence and activity of Nitrospina bacteria that are tolerant to environmental stress. This in turn was positively influenced by the presence of ammonia- or urea-producing macrobiota. PMID- 29799173 TI - Virulence of Melissococcus plutonius and secondary invaders associated with European foulbrood disease of the honey bee. AB - European foulbrood is a globally distributed brood disease affecting honey bees. It may lead to lethal infections of larvae and, in severe cases, even to colony collapse. Lately, a profound genetic and phenotypic diversity was documented for the causative agent Melissococcus plutonius. However, experimental work on the impact of diverse M. plutonius strains on hosts with different genetic background is completely lacking and the role of secondary invaders is poorly understood. Here, we address these issues and elucidate the impact and interaction of both host and pathogen on one another. Moreover, we try to unravel the role of secondary bacterial invasions in foulbrood-diseased larvae. We employed in vitro infections with honey bee larvae from queens with different genetic background and three different M. plutonius strains. Larvae infection experiments showed host-dependent survival dynamics although M. plutonius strain 49.3 consistently had the highest virulence. This pattern was also reflected in significantly reduced weights of 49.3 strain-infected larvae compared to the other treatments. No difference was found in groups additionally inoculated with a secondary invader (Enterococcus faecalis or Paenibacillus alvei) neither in terms of larval survival nor weight. These results suggest that host background contributes markedly to the course of the disease but virulence is mainly dependent on pathogen genotype. Secondary invaders following a M. plutonius infection do not increase disease lethality and therefore may just be a colonization of weakened and immunodeficient, or dead larvae. PMID- 29799172 TI - Outbreaks of abortions by Coxiella burnetii in small ruminant flocks and a longitudinal serological approach on archived bulk tank milk suggest Q fever emergence in Central Portugal. AB - Q fever is a worldwide zoonotic infectious disease caused by Coxiella burnetii and sheep and goats are known to be the main reservoir for human infection. This study describes the epidemiological and laboratory findings of C. burnetii outbreaks affecting sheep and goat flocks and also provides the results of a prospective serosurvey in bulk tank milk samples to assess C. burnetii circulation in a population of sheep living in close contact to the human population in Central Portugal. In the epizooties, C. burnetii was identified in tissues of the resulting abortions by qPCR. As for the serological survey, 10.2% (95%CI: 4.5-19.2) of the 78 bulk tank milk samples collected in 2015 presented IgG antibodies against C. burnetii. The same farms were visited and sampled in 2016 and 25.6% (95%CI: 16.4-36.8) were positive. This steep increase in the number of anti-C. burnetii farms between the 2015 and 2016 collections showed to be statistically significant (p = 0.020) and is strongly suggestive of Q fever emergence in Central Portugal. Measures on animal health and on disease spread control to the human population should be considered. PMID- 29799174 TI - VEGFR Recognition Interface of a Proangiogenic VEGF-Mimetic Peptide Determined In Vitro and in the Presence of Endothelial Cells by NMR Spectroscopy. AB - QK peptide is a vascular endothelial growth factor (VEGF)-mimetic molecule with significant proangiogenic activity. In particular, QK is able to bind and activate VEGF receptors (VEGFRs) to stimulate a functional response in endothelial cells. To characterize the peptide bioactivity and its molecular recognition properties, a detailed picture of the interaction between peptide QK and VEGF receptors is reported. By combining NMR spectroscopy studies in solution on the purified receptor and in the presence of intact endothelial cells, a molecular description of the binding interaction between peptide QK and VEGFR2 in the cellular context is obtained. These results reveal useful insights into the peptide biological mechanism, which opens the way to further optimization of this class of VEGF-mimicking peptides. PMID- 29799175 TI - Are We There Yet? How and When Specific Biotechnologies Will Improve Human Health. AB - Patient X: A 67-year-old Caucasian man slips on a patch of ice. He has abrasions to his hands and has sustained significant damage to his hip. At the emergency room, he informs clinicians he takes atorvastatin, metformin, and glimepiride to treat hypertension and Type 2 Diabetes Mellitus (T2DM). X-rays reveal a fractured hip, which will require total hip replacement surgery. PMID- 29799176 TI - Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countries-Survey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology. AB - INTRODUCTION: Women with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. MATERIAL AND METHODS: The Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. RESULTS: The questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15 120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. CONCLUSION: More than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced. PMID- 29799177 TI - Do wild boar movements drive the spread of African Swine Fever? AB - The spatial behaviour of hosts can seriously affect the transmission of pathogens and spatial spread of diseases. Understanding the relationship between host movements and disease dynamics is of prime importance for optimizing disease control efforts. African swine fever (ASF), a devastating disease of wild and domestic suids, has been spreading continuously through eastern Europe since 2007. The wild boar (Sus scrofa) has been implicated in the epidemiology of this disease, but the role of wild boar movements in ASF dynamics and spread has not been studied and remains largely speculative. Here, we examined whether monthly parameters of wild boar movements (dispersal distance of yearlings, home range size of adult males and females) can explain variation in the spatio-temporal dynamics of the ASF outbreak in the wild boar population in north-eastern Poland, 2014-2015. We expected to observe a positive relationship between host mobility and disease spread. Contrary to our expectations, we found that movements of wild boar, despite their seasonal variation, were poor predictors of ASF dynamics in space and time. During the 2 years of the study, ASF spread gradually at a steady pace of 1.5 km/month without significant changes across seasons. None of the analysed movement parameters explained variation in the measures of ASF occurrence and spread (i.e., number of cases, prevalence, size and expansion rate of the outbreak area). We believe that the factor limiting the influence of host movements on ASF dynamics is the severity of the disease, which quickly hampers extensive movements and restricts disease transmission to only the most immediate individuals. Three natural factors constrain direct disease transmission: wild boar social structure, the short duration of low-level virus shedding and high virus-induced lethality, followed by indirect transmission through infected carcasses. These most likely shape the gradual spread of ASF in space and its persistence in already infected areas. PMID- 29799178 TI - Using hermeneutic phenomenology and the ethnographic principle of cultural interpretation with Malaysian nurses. AB - BACKGROUND: The interpretive paradigm and hermeneutic phenomenological design are the most popular methods used in international cross-cultural research in healthcare, nurse education and nursing practice. Their inherent appeal is that they help researchers to explore experiences. The ethnographic principle of cultural interpretation can also be used to provide meaning, clarity and insight. AIM: To examine the use of hermeneutic phenomenology and the ethnographic principle of cultural interpretation in a research study conducted with Malaysian nurses on part-time, transnational, post-registration, top-up nursing degree programmes provided by one Australian and two UK universities. DISCUSSION: To enable the researcher to undertake international cross-cultural research and illuminate Malaysian nurses' views for the reader, cultural aspects need to be considered, as they will influence the information participants provide. Useful strategies that western researchers can adopt to co-create research texts with interviewees are outlined. The paradigm and research designs used in the study revealed the views and experiences of Malaysian nurses. CONCLUSION: Hermeneutic phenomenology enabled the exploration of participants' experiences, and the ethnographic principle of cultural interpretation enabled the researcher's reflexivity to provide emic and etic views for the reader. IMPLICATIONS FOR PRACTICE: This paper adds to the discussion of the paradigms and research designs used for international, cross-cultural research in Asia. It identifies the influence participants' cultural values have on their confidence and level of disclosure with western researchers. PMID- 29799179 TI - Clinical evaluation of diabetic neuropathy in adult patients with type 1 diabetes and its possible association with insulin resistance AB - : Background: In Mexico, there is a lack of information regarding the prevalence and characteristics of Diabetic Neuropathy (DN) in patients with type 1 diabetes (T1D).Although it was, considered as a country with low-incidence of T1D, recent publications show that T1D frequency is under-represented. The aim of this paper is to describe the frequency and severity of DN in patients with T1D using a clinical scale and assess its possible association with insulin resistance. : Methods: We evaluated 48 patients from T1D Clinic. We assessed clinical and biochemical characteristics and determined insulin resistance through estimated glucose dispose rate (eGDR). Patients underwent a neurologic evaluation using a previously validated score. Results: Seventy-three percent of patients had DN (54% mild and 19% moderate neuropathy). Twenty-nine percent of total population had Metabolic Syndrome. Major predictor factors for DN were the presence of diabetes for more than 13 years (OR 4.6, CI95%: 1.09-15.7), achieving treatment goals during the first 5 years (OR 0.22, CI95%: 0.05-0.87) and eGDR > 7.32 mg/kg/min (OR 0.096, CI95%: 0.011-0.81). Conclusions: The clinical scale performed in this study is a useful screening tool for DN in adults with long standing T1D. DN is more frequent in patients with longer evolution of diabetes and poor glucose control during the initial years after diagnosis as expected, but insulin resistance should also be considered as an additional risk factor in this group. PMID- 29799180 TI - High-Throughput Fabrication of Ultradense Annular Nanogap Arrays for Plasmon Enhanced Spectroscopy. AB - The confinement of light into nanometer-sized metallic nanogaps can lead to an extremely high field enhancement, resulting in dramatically enhanced absorption, emission, and surface-enhanced Raman scattering (SERS) of molecules embedded in nanogaps. However, low-cost, high-throughput, and reliable fabrication of ultra high-dense nanogap arrays with precise control of the gap size still remains a challenge. Here, by combining colloidal lithography and atomic layer deposition technique, a reproducible method for fabricating ultra-high-dense arrays of hexagonal close-packed annular nanogaps over large areas is demonstrated. The annular nanogap arrays with a minimum diameter smaller than 100 nm and sub-1 nm gap width have been produced, showing excellent SERS performance with a typical enhancement factor up to 3.1 * 106 and a detection limit of 10-11 M. Moreover, it can also work as a high-quality field enhancement substrate for studying two dimensional materials, such as MoSe2. Our method provides an attractive approach to produce controllable nanogaps for enhanced light-matter interaction at the nanoscale. PMID- 29799181 TI - Stretchable Transparent Electrodes with Solution-Processed Regular Metal Mesh for an Electroluminescent Light-Emitting Film. AB - We report stretchable metal-mesh transparent electrodes (TEs) with excellent electrical conductivity (<2 Omega/sq) and optical transparency (>80%) under up to 55% strain. The figures of merit on these electrodes, as defined as the ratio between electrical conductivity and optical conductivity, are among the highest reported for stretchable TEs under moderate stretching. Moreover, we demonstrate their application in a stretchable electroluminescent (EL) light-emitting film as top and bottom electrodes. EL lighting devices require low-resistance electrodes to unleash their potential for large-area low-power-consumption applications, in which our highly conductive and transparent stretchable TEs provide an edge on other competitor approaches. Importantly, our stretchable metal-mesh electrodes are fabricated through a vacuum-free solution-processed approach that is scalable for cost-effective mass production. We also investigate the fracture and fatigue mechanisms of stretchable metal-mesh electrodes with various mesh patterns and observe different behaviors under one-time and cyclic stretching conditions. Our solution-processed fabrication method, failure mechanism investigation, and device demonstration for metal-mesh stretchable TEs will facilitate the adoption of this promising high-performance approach in stretchable and wearable electronics applications. PMID- 29799182 TI - Rational Design of Hierarchical Nanotubes through Encapsulating CoSe2 Nanoparticles into MoSe2/C Composite Shells with Enhanced Lithium and Sodium Storage Performance. AB - Transition-metal diselenides have been extensively studied as desirable anode candidates for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of their high theoretical capacities. However, it is of great challenge to achieve satisfactory cycling performance, especially for larger sodium ion storage, originated from electrode deterioration upon large volume change. Herein, we reported the construction of hierarchical tubular hybrid nanostructures through encapsulating CoSe2 nanoparticles into MoSe2/C composite shells via a simple two-step strategy including a hydrothermal method followed by vapor-phase selenization process. The unique tubular structure enables the highly reversible Li/Na storage with high specific capacity, enhanced cycling stability, and superior rate performance. It is indicated that the contribution of partial pseudocapacitive behavior greatly improves the rate capability for SIBs, where a high capacity retention of 81.5% can be obtained when the current densities range from 0.1 to 3 A g-1 (460 mA h g-1 at 0.1 A g-1 vs 379 mA h g-1 at 3 A g-1). This work provides an effective design rationale on transition-metal diselenide-based tubular nanostructures as superior hosts for both Li and Na ions, which could push forward the development of practical applications of transition-metal diselenide-based anodes in LIBs and SIBs. PMID- 29799183 TI - Nature-Inspired Capillary-Driven Welding Process for Boosting Metal-Oxide Nanofiber Electronics. AB - Recently, semiconducting nanofiber networks (NFNs) have been considered as one of the most promising platforms for large-area and low-cost electronics applications. However, the high contact resistance among stacking nanofibers remained to be a major challenge, leading to poor device performance and parasitic energy consumption. In this report, a controllable welding technique for NFNs was successfully demonstrated via a bioinspired capillary-driven process. The interfiber connections were well-achieved via a cooperative concept, combining localized capillary condensation and curvature-induced surface diffusion. With the improvements of the interfiber connections, the welded NFNs exhibited enhanced mechanical property and high electrical performance. The field effect transistors (FETs) based on the welded Hf-doped In2O3 (InHfO) NFNs were demonstrated for the first time. Meanwhile, the mechanisms involved in the grain boundary modulation for polycrystalline metal-oxide nanofibers were discussed. When the high-k ZrO x dielectric thin films were integrated into the FETs, the field-effect mobility and operating voltage were further improved to be 25 cm2 V 1 s-1 and 3 V, respectively. This is one of the best device performances among the reported nanofibers-based FETs. These results demonstrated the potencies of the capillary-driven welding process and grain-boundary modulation mechanism for metal-oxide NFNs, which could be applicable for high-performance, large-scale, and low-power functional electronics. PMID- 29799184 TI - Dendritic Mesoporous Silica Nanoparticles with Abundant Ti4+ for Phosphopeptide Enrichment from Cancer Cells with 96% Specificity. AB - Selective enrichment and sensitive detection of phosphopeptides are of great significance in many bioapplications. In this work, dendritic mesoporous silica nanoparticles modified with polydopamine and chelated Ti4+ (denoted DMSNs@PDA Ti4+) were developed to improve the enrichment selectivity of phosphopeptides. The unique central-radial pore structures endowed DMSNs@PDA-Ti4+ with a high surface area (362 m2 g-1), a large pore volume (1.37 cm3 g-1), and a high amount of chelated Ti4+ (75 MUg mg-1). Compared with conventional mesoporous silica based materials with the same functionalization (denoted mSiO2@PDA-Ti4+) and commercial TiO2, DMSNs@PDA-Ti4+ showed better selectivity and a lower detection limit (0.2 fmol/MUL). Moreover, 2422 unique phosphopeptides were identified from HeLa cell extracts with a high specificity (>95%) enabled by DMSNs@PDA-Ti4+, better than those in previous reports. PMID- 29799185 TI - Arginine "Magic": Guanidinium Like-Charge Ion Pairing from Aqueous Salts to Cell Penetrating Peptides. AB - It is a textbook knowledge that charges of the same polarity repel each other. For two monovalent ions in the gas phase at a close contact this repulsive interaction amounts to hundreds of kilojoules per mole. In aqueous solutions, however, this Coulomb repulsion is strongly attenuated by a factor equal to the dielectric constant of the medium. The residual repulsion, which now amounts only to units of kilojoules per mole, may be in principle offset by attractive interactions. Probably the smallest cationic pair, where a combination of dispersion and cavitation forces overwhelms the Coulomb repulsion, consists of two guanidinium ions in water. Indeed, by a combination of molecular dynamics with electronic structure calculations and electrophoretic, as well as spectroscopic, experiments, we have demonstrated that aqueous guanidinium cations form (weakly) thermodynamically stable like-charge ion pairs. The importance of pairing of guanidinium cations in aqueous solutions goes beyond a mere physical curiosity, since it has significant biochemical implications. Guanidinium chloride is known to be an efficient and flexible protein denaturant. This is due to the ability of the orientationally amphiphilic guanidinium cations to disrupt various secondary structural motifs of proteins by pairing promiscuously with both hydrophobic and hydrophilic groups, including guanidinium-containing side chains of arginines. The fact that the cationic guanidinium moiety forms the dominant part of the arginine side chain implies that the like-charge ion pairing may also play a role for interactions between peptides and proteins. Indeed, arginine-arginine pairing has been frequently found in structural protein databases. In particular, when strengthened by a presence of negatively charged glutamate, aspartate, or C-terminal carboxylic groups, this binding motif helps to stabilize peptide or protein dimers and is also found in or near active sites of several enzymes. The like-charge pairing of the guanidinium side-chain groups may also hold the key to the understanding of the arginine "magic", that is, the extraordinary ability of arginine-rich polypeptides to passively penetrate across cellular membranes. Unlike polylysines, which are also highly cationic but lack the ease in crossing membranes, polyarginines do not exhibit mutual repulsion. Instead, they accumulate at the membrane, weaken it, and might eventually cross in a concerted, "train-like" manner. This behavior of arginine-rich cell penetrating peptides can be exploited when devising smart strategies how to deliver in a targeted way molecular cargos into the cell. PMID- 29799187 TI - Nontargeted Identification of Tracer Incorporation in High-Resolution Mass Spectrometry. AB - "Fluxomics" refers to the systematic analysis of metabolic fluxes in a biological system and may uncover novel dynamic properties of metabolism that remain undetected in conventional metabolomic approaches. In labeling experiments, tracer molecules are used to track changes in the isotopologue distribution of metabolites, which allows one to estimate fluxes in the metabolic network. Because unidentified compounds cannot be mapped on pathways, they are often neglected in labeling experiments. However, using recent developments in de novo annotation may allow to harvest the information present in these compounds if they can be identified. Here, we present a novel tool (HiResTEC) to detect tracer incorporation in high-resolution mass spectrometry data sets. The software automatically extracts a comprehensive, nonredundant list of all compounds showing more than 1% tracer incorporation in a nontargeted fashion. We explain and show in an example data set how mass precision and other filter heuristics, calculated on the raw data, can efficiently be used to reduce redundancy and noninformative signals by 95%. Ultimately, this allows to quickly investigate any labeling experiment for a complete set of labeled compounds (here 149) with acceptable false positive rates. We further re-evaluate a published data set from liquid chromatography-electrospray ionization (LC-ESI) to demonstrate broad applicability of our tool and emphasize importance of quality control (QC) tests. HiResTEC is provided as a package in the open source software framework R and is freely available on CRAN. PMID- 29799186 TI - Brain Targeting Delivery Facilitated by Ligand-Functionalized Layered Double Hydroxide Nanoparticles. AB - A delivery platform with highly selective permeability through the blood-brain barrier (BBB) is essential for brain disease treatment. In this research, we designed and prepared a novel target nanoplatform, that is, layered double hydroxide (LDH) nanoparticle conjugated with targeting peptide-ligand Angiopep-2 (Ang2) or rabies virus glycoprotein (RVG) via intermatrix bovine serum albumin for brain targeting. In vitro studies show that functionalization with the target ligand significantly increases the delivery efficiency of LDH nanoparticles to the brain endothelial (bEnd.3) cells and the transcytosis through the simulated BBB model, that is, bEnd.3 cell-constructed multilayer membrane. In vivo confocal neuroimaging of the rat's blood-retina area dynamically demonstrates that LDH nanoparticles modified with peptide ligands have shown a prolonged retention period within the retina vessel in comparison with the pristine LDH group. Moreover, Ang2-modified LDH nanoparticles are found to more specifically accumulate in the mouse brain than the control and RVG-modified LDH nanoparticles after 2 and 48 h intravenous injection. All these findings strongly suggest that Ang2-modified LDHs can serve as an effective targeting nanoplatform for brain disease treatment. PMID- 29799188 TI - Nanoscale Investigation into the Cellular Response of Glioblastoma Cells Exposed to Protons. AB - Exposure to ionizing radiation can induce cellular defense mechanisms including cell activation and rapid proliferation prior to metastasis and in extreme cases can result in cell death. Herewith we apply infrared nano- and microspectroscopy combined with multidimensional data analysis to characterize the effect of ionizing radiation on single glioblastoma nuclei isolated from cells treated with 10 Gy of X-rays or 1 and 10 Gy of protons. We observed chromatin fragmentation related to the formation of apoptotic bodies following X-ray exposure. Following proton irradiation we detected evidence of a DNA conformational change (B-DNA to A-DNA transition) related to DNA repair and accompanied by an increase in protein content related to the synthesis of peptide enzymes involved in DNA repair. We also show that proton exposure can increase cholesterol and sterol ester synthesis, which are important lipids involved in the metastatic process changing the fluidity of the cellular membrane in preparation for rapid proliferation. PMID- 29799189 TI - Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs). AB - The 25 bitter taste receptors (T2Rs) in humans are novel players in mediating host-pathogen responses in the airways and innate immunity. The chemosensory T2Rs are expressed in different extraoral tissues and perform diverse pathophysiological roles from mediating bronchodilation to detecting bacterial infection in the airways. T2Rs were suggested to be activated by multiple bacterial quorum sensing molecules (QSMs). However, whether bacterial QSMs bind to T2Rs and the structural features on T2Rs has not yet been characterized. Here, we analyzed the taste sensory profiles of QSMs including acyl homoserine lactones (C4-AHL, C8-AHL, and 3-oxo-C12-AHL) and hydroxyquinolones (HHQ and NHQ) predominantly secreted by Gram-negative bacteria and characterized the candidate T2Rs interacting with different QSMs using structure-function approaches. The potency of the above QSMs for T2Rs significantly expressed in the airways, namely T2R4, T2R14, and T2R20, was characterized. 3-Oxo-C12-AHL activated T2R4, T2R14, and T2R20, while C8-AHL activated T2R4 and T2R14 with strong potency. The T2R amino acid residues involved in the interactions were characterized by molecular model-guided site-directed mutagenesis. AHLs bind to a similar orthosteric site present on the extracellular surface in all three T2Rs with significant contributions from residues in extracellular loop 2. Our results reveal the mode of binding of AHLs for different T2Rs and provide biochemical insights into their interactions. This study will facilitate mechanistic studies aimed at understanding the role of these T2Rs as "sensors" of bacteria and in host pathogen interactions. PMID- 29799190 TI - Extreme Ultraviolet Radiation: A Means of Ion Activation for Tandem Mass Spectrometry. AB - Tandem mass spectrometry has long been established as a corner stone of analytical and structural chemistry. Fast radical-directed dissociation, produced by electron-transfer and electron-capture dissociation (ETD and ECD) has been shown to provide important complementary information to collision-induced dissociation (CID). We report the first application of extreme-ultraviolet (XUV) lamps to tandem mass spectrometry. These discharge lamps are versatile, robust, and low-cost sources of energetic photons (40-80 nm). The coupling of the discharge lamp with a Waters Synapt G2-Si Q-ToF mass spectrometer is achieved through a specific trapping scheme in the TriWave region of the instrument, allowing efficient irradiation of the precursor ions. Rich radical-directed dissociation was produced for a number of model compounds, providing unique, complementary information to existing dissociation techniques. PMID- 29799191 TI - Camptothecin Efficacy to Poison Top1 Is Altered by Bisphenol A in Mouse Embryonic Fibroblasts. AB - Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked to obesity, diabetes, and breast and reproductive system cancers. Resistance to chemotherapeutic agents has also been shown in cancer cell models. Here, we investigated BPA's ability to confer resistance to camptothecin (CPT) in mouse embryonic fibroblasts (MEFs). MEFs are sensitive to CPT; however, co-exposure of BPA with CPT improved cell survival. Co-exposure significantly reduced Top1-DNA adducts, decreasing chromosomal aberrations and DNA strand break formation. This decrease occurs despite BPA treatment increasing the protein levels of Top1. By examining chromatin structure after BPA exposure, we determined that widespread compaction and loss of nuclear volume occurs. Therefore, BPA reduced CPT activity by reducing the accessibility of DNA to Top1, inhibiting DNA adduct formation, the generation of toxic DNA strand breaks, and improving cell survival. PMID- 29799192 TI - Correction to "Pectic Polysaccharides from Panax ginseng as the Antirotavirus Principals in Ginseng". PMID- 29799194 TI - Ruthenium(II)-Catalyzed Regioselective-Controlled Allenylation/Cyclization of Benzimides with Propargyl Alcohols. AB - A ruthenium(II)-catalyzed cyclization of benzimidates with substituted propargyl alcohols to provide 3,4-disubstituted 1-alkoxy isoquinolines in a highly selective manner via the C-H allenylation is described. The proposed reaction mechanism of the ruthenium(II)-catalyzed cyclization reaction is strongly supported by the isolation of the key ruthenacycle intermediate, deuterium labeling studies, and detailed DFT calculations including the transition states. PMID- 29799193 TI - Assessment of the Antigenotoxic Activity of Poly(d,l-lactic- co-glycolic acid) Nanoparticles Loaded with Caffeic Acid Phenethyl Ester Using the Ames Salmonella/Microsome Assay. AB - In the present study, the antigenotoxic activity of poly(d,l-lactic- co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with caffeic acid phenethyl ester (CAPE) was investigated in comparison to free CAPE using the Ames Salmonella/microsome assay. Additionally, to elucidate the impacts of the type of solvent effect on antigenotoxic activity, the following systems were tested: CAPE in water (poor solvent), ethyl alcohol (good solvent), and PLGA NPs (unknown). The effect of the NP system on solubility was investigated for the first time by assessing the antigenotoxic potential. In this study, the CAPE/PLGA NPs were synthesized using an oil-in-water (o/w) single-emulsion solvent evaporation method with an average size of 206.2 +/- 1.2 nm, zeta potential of -19.8 +/- 2.5 mV, encapsulation efficiency of 87.2 +/- 2.5%, and drug loading of 53.3 +/- 1.8%. According to the results of the antigenotoxic activity, the highest antimutagenic activity in both applied strains was found for CAPE in ethanol, and the lowest activity was detected for CAPE in water. Our study has shown that NP systems exhibit high antigenotoxic activity, which is similar to the results of CAPE dissolved in ethanol. These results have shown that NP systems increase biological activity of hydrophobic substances by increasing their solubility and that the use of PLGA instead of organic solvents in drug production may provide an increase in their medical utility. PMID- 29799195 TI - Iridoids from the Roots of Patrinia scabra and Their Inhibitory Potential on LPS Induced Nitric Oxide Production. AB - An activity-guided fractionation procedure of the 70% aqueous EtOH extract from the roots of Patrinia scabra led to the isolation and characterization of five new iridoids, patriscabrins A-E (1-5), along with 13 known compounds. The structures of 1-5 were determined by interpretation of spectroscopic data, particularly by 1D and 2D NMR, ECD, and VCD studies. Thereafter, isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Of these, the new iridoids 2 and 5 and the known lignan patrineolignan B (6) exhibited IC50 values of 14.7 to 17.8 MUM. PMID- 29799196 TI - Stereoselectivity Switch in the Trapping of Polar Organometallics with Andersen's Reagent-Access to Highly Stereoenriched Transformable Biphenyls. AB - The trapping of racemic polar carbometallic species with (-)-menthyl ( SS)- p toluenesulfinate (Andersen's reagent) typically proceeds with a very low level of resolution. In this paper, we describe a strategy that allows access to highly atropo-enriched and functionalizable biphenyls by means of Andersen's reagent under kinetic resolution conditions. In particular, useful enantiopure 2 iodobiphenyls could be obtained and were employed in a challenging hypervalent iodine-catalyzed oxidation reaction. PMID- 29799197 TI - DNA-Functionalized, Bivalent Proteins. AB - Bivalent DNA conjugates of beta-galactosidase (betaGal), having pairs of oligonucleotides positioned closely on opposing faces of the protein, have been synthesized and characterized. These structures, due to their directional bonding characteristics, allow for the programmable access of one-dimensional protein materials. When conjugates functionalized with complementary oligonucleotides are combined under conditions that support DNA hybridization, periodic wire-type superstructures consisting of aligned proteins form. These structures have been characterized by gel electrophoresis, cryo-transmission electron microscopy, and negative-stain transmission electron microscopy. Significantly, melting experiments of complementary building blocks display narrowed and elevated melting transitions compared to the free duplex DNA, further supporting the formation of the designed binding mode, and unambiguously characterizing their association as DNA-mediated. These novel structures illustrate, for the first time, that directional DNA bonding can be realized with only a pair of DNA modifications, which will allow one to engineer directional interactions and realize new classes of superstructures not possible simply through shape control or isotropically functionalized materials. PMID- 29799198 TI - Covalent and Ionic Capacity of MOFs To Sorb Small Gas Molecules. AB - In this work, the aim is to characterize how an Fe-based metal-organic framework (MOF) behaves when gases, like carbon dioxide, are inserted through their channels and to characterize the nature and strength of those interactions. Despite the computational nature of the project, it is based on the experimental results obtained in 2016 by Minguez-Espallargas and co-workers ( J. Am. Chem. Soc. 2013, 135, 15986 - 15989 ). Those MOFs were found to selectively allocate/adsorb CO2, having as a drawback that apparently each cavity allocates only one CO2 molecule. Despite truncating the MOF to its unitary cell, the whole cavity of the MOF can be described in detail by precise ab initio calculations. Another computational goal is to unravel why experimentally CO2 was preferred with respect to N2, and for the sake of consistency, a list of common gases will be further studied, such as H2, O2, H2O, CH4, C2H6, N2O, or NO. PMID- 29799199 TI - Evolved Minimal Frustration in Multifunctional Biomolecules. AB - Protein folding is often viewed in terms of a funneled potential or free energy landscape. A variety of experiments now indicate the existence of multifunnel landscapes, associated with multifunctional biomolecules. Here, we present evidence that these systems have evolved to exhibit the minimal number of funnels required to fulfill their cellular functions, suggesting an extension to the principle of minimum frustration. We find that minimal disruptive mutations result in additional funnels, and the associated structural ensembles become more diverse. The same trends are observed in an atomic cluster. These observations suggest guidelines for rational design of engineered multifunctional biomolecules. PMID- 29799200 TI - Gating Mechanism of Aquaporin Z in Synthetic Bilayers and Native Membranes Revealed by Solid-State NMR Spectroscopy. AB - Aquaporin Z (AqpZ) is an integral membrane protein that facilitates transport of water across Escherichia coli cells with a high rate. Previously, R189, a highly conserved residue of the selective filter of AqpZ, was proposed as a gate within the water channel on the basis of the observation of both open and closed conformations of its side chain in different monomers of an X-ray structure, and the observation of rapid switches between the two conformations in molecular dynamic simulations. However, the gating mechanism of the R189 side chain remains controversial since it is unclear whether the different conformations observed in the X-ray structure is due to different functional states or is a result of perturbation of non-native detergent environments. Herein, in native-like synthetic bilayers and native E. coli membranes, a number of solid-state NMR techniques are employed to examine gating mechanism of the R189 side chain of AqpZ. One R189 side-chain conformation is highly evident since only a set of peaks corresponding to the R189 side chain is observed in 2D 15N-13C spectra. The immobility of the R189 side chain is detected by 1H-15N dipolar lineshapes, excluding the possibility of the rapid switches between the two side-chain conformations. High-resolution monomeric structure of AqpZ, determined by CS Rosetta calculations using experimentally measured distance restraints related to the R189 side chain, reveals that this side chain is in an open conformation, which is further verified by its water accessibility. All the solid-state NMR experimental results, combining with water permeability essay, suggest a permanently open conformation of the R189 side chain in the synthetic bilayer and native membranes. This study provides new structural insights into the gating mechanism of aquaporins and highlights the significance of lipid bilayer environments in elucidating the molecular mechanism of membrane proteins. PMID- 29799201 TI - Rational Design of Co(II) Dominant and Oxygen Vacancy Defective CuCo2O4@CQDs Hollow Spheres for Enhanced Overall Water Splitting and Supercapacitor Performance. AB - The hierarchical CuCo2O4@carbon quantum dots (CQDs) hollow microspheres constructed by 1D porous nanowires have been successfully prepared through a simple CQDs-induced hydrothermal self-assembly technique. XPS analysis shows the CuCo2O4@CQDs possesses the Co(II)-rich surface associated with the oxygen vacancies, which can effectively boost the Faradaic reactions and oxygen evolution reaction (OER) activity. For example, the as-synthesized 3D porous CuCo2O4@CQDs electrode exhibits high activity toward overall electrochemical water splitting, for example, an overpotential of 290 mV for OER and 331 mV for hydrogen evolution reaction (HER) in alkaline media have been achieved at 10 mA cm-2, respectively. Furthermore, an asymmetric supercapacitor (ASC) (CuCo2O4@CQDs//CNTs) delivers a high energy density of 45.9 Wh kg-1 at 763.4 W kg 1, as well as good cycling ability. The synergy of Co(II)-rich surface, oxygen vacancies, and well-defined 3D hollow structures facilitates the subsequent surface electrochemical reactions. This work presents a facile method to fabricate energetic nanocomposites with highly reactive, durable, and universal functionalities. PMID- 29799202 TI - Laser Tailoring the Surface Chemistry and Morphology for Wear, Scale and Corrosion Resistant Superhydrophobic Coatings. AB - A strategy, combining laser chemical modification with laser texturing, followed by chemisorption of the fluorinated hydrophobic agent was used to fabricate the series of superhydrophobic coatings on an aluminum alloy with varied chemical compositions and parameters of texture. It was shown that high content of aluminum oxynitride and aluminum oxide formed in the surface layer upon laser treatment allows solving the problem of enhancement of superhydrophobic coating resistance to abrasive loads. Besides, the multimodal structure of highly porous surface layer leads to self-healing ability of fabricated coatings. Long-term behavior of designed coatings in "hard" hot water with an essential content of calcium carbonate demonstrated high antiscaling resistance with self-cleaning potential against solid deposits onto the superhydrophobic surfaces. Study of corrosion protection properties and the behavior of coatings at long-term contact with 0.5 M NaCl solution indicated extremely high chemical stability and remarkable anticorrosion properties. PMID- 29799203 TI - Regio- and Enantioselective Rhodium-Catalyzed Allylic Alkylation of Racemic Allylic Alcohols with 1,3-Diketones. AB - Highly regio- and enantioselective rhodium-catalyzed allylic alkylation of 1,3 diketones with racemic secondary allylic alcohols is reported. In the presence of a Rh-catalyst derived from the Carreira (P, olefin)-ligand and TFA as an additive, chiral branched alpha-allylated 1,3-diketones could be obtained in good to excellent yields, with excellent regio- and enantioselectivity ( b/ l > 19/1, 86-98% ee). The direct utilization of allyl alcohols as electrophiles represents an improvement from the viewpoint of an atom economy. Both aryl- and aliphatic substituted allyl alcohols are suitable substrates with excellent reaction outcomes. This reaction features mild conditions, broad substrate scope, and readily available substrates. PMID- 29799204 TI - Ultrafast X-ray Absorption Near Edge Structure Reveals Ballistic Excited State Structural Dynamics. AB - Polarized ultrafast time-resolved X-ray absorption near edge structure (XANES) allows characterization of excited state dynamics following excitation. Excitation of vitamin B12, cyanocobalamin (CNCbl), in the alphabeta-band at 550 nm and the gamma-band at 365 nm was used to uniquely resolve axial and equatorial contributions to the excited state dynamics. The structural evolution of the excited molecule is best described by a coherent ballistic trajectory on the excited state potential energy surface. Prompt expansion of the Co cavity by ca. 0.03 A is followed by significant elongation of the axial bonds (>0.25 A) over the first 190 fs. Subsequent contraction of the Co cavity in both axial and equatorial directions results in the relaxed S1 excited state structure within 500 fs of excitation. PMID- 29799206 TI - Surface Engineering of Bromine-Based Plasma Polymer Films: A Step toward High Thiol Density Containing Organic Coatings. AB - Nowadays, the development of synthetic methods regarding the fabrication of -SH containing organic coatings continues to attract a considerable attention. Among the potential techniques, the plasma polymerization appears as one of the most promising method but the difficulty to control the chemical composition of the layers is highly limiting. In this context, in this work, we report on an original method combining dry and wet chemistry approaches in view of selectively incorporating -SH functions in organic coatings. Our strategy is based on the (i) synthesis of a bromine-containing plasma polymer film, followed by (ii) a selective grafting of dithiol-based molecule on C-Br bond. Investigating the plasma polymerization process has revealed that, in our experimental window, the load of energy in the discharge has little influence on the chemical composition as well as on the cross-linking degree of the layers. This behavior is explained by considering the concomitant influence of the gas-phase reactions and the supply of energy to the growing film through ion bombardment. With regard to the functionalization strategy, based on comparative X-ray photoelectron spectroscopy measurements, it has been unambiguously demonstrated that a selective reaction between propanedithiol and the C-Br bond acting as the reactive center takes place resulting in the removing of the bromine atom and the incorporation of -SH groups in the PPF. Depending on the grafting reaction duration, the relative proportion of carbon bearing the -SH group is found to evolve from 4 to 6%. On the other hand, the dissolution of unbounded bromine-based species in the liquid medium during the grafting procedure is also evidenced. The whole set of our results clearly demonstrates the attractiveness of our strategy paving the way for new development in the fabrication of -SH-rich-containing organic thin films. PMID- 29799205 TI - Lithocholic Acid-Based Peptide Delivery System for an Enhanced Pharmacological and Pharmacokinetic Profile of Xenopus GLP-1 Analogs. AB - GLP-1 analogs suffer from the main disadvantage of a short in vivo half-life. Lithocholic acid (LCA), one of the four main bile acids in the human body, possesses a high albumin binding rate. We therefore envisioned that a LCA-based peptide delivery system could extend the half-life of GLP-1 analogs by facilitating the noncovalent binding of peptides to human serum albumin. On the basis of our previously identified Xenopus GLP-1 analogs (1-3), a series of LCA modified Xenopus GLP-1 conjugates were designed (4a-4r), and the bioactivity studies of these conjugates were performed to identify compounds with balanced in vitro receptor activation potency and plasma stability. 4c, 4i, and 4r were selected, and their LCA side chains were optimized to further increase their stability, affording 5a-5c. Compound 5b showed a more increased albumin affinity and prolonged in vitro stability than that of 4i and liraglutide. In db/ db mice, 5b exhibited comparable hypoglycemic and insulinotropic activity to liraglutide and semaglutide. Importantly, the enhanced albumin affinity of 5b resulted in a prolonged in vivo antidiabetic duration. Finally, chronic treatment investigations of 5b demonstrated the therapeutic effects of 5b on HbA1c, body weight, blood glucose, and pancreatic endocrine deficiencies on db/ db mice. Our studies revealed 5b as a promising antidiabetic candidate. Furthermore, our study suggests the derivatization of Xenopus GLP-1 analogs with LCA represents an effective strategy to develop potent long-acting GLP-1 receptor agonists for the treatment of type 2 diabetes. PMID- 29799207 TI - Total Synthesis of Originally Proposed and Revised Structure of Hetiamacin A. AB - The first total synthesis of the originally proposed and correct structures of hetiamacin A has been accomplished via Wittig olefination and Sharpless asymmetric dihydroxylation reaction. These total syntheses culminated in the stereostructural confirmation of the reassignment of hetiamacin A. PMID- 29799208 TI - Strategies for Preparing Graphene Liquid Cells for Transmission Electron Microscopy. AB - A graphene liquid cell for transmission electron microscopy (TEM) uses one or two graphene sheets to separate the liquid from the vacuum in the microscope. In principle, graphene is an excellent material for such an application because it allows the highest possible spatial resolution, provides a flexible covering foil, and effectively protects the liquid from evaporating. Examples in open literature have demonstrated atomic-resolution TEM using small liquid pockets and the coverage of whole biological cells with graphene sheets. A total of three different basic types of liquid cells are discerned: (i) one graphene sheet is used to cover a liquid sample supported by a thin membrane of another material (for example, silicon nitride, SiN), (ii) two graphene sheets pressed together leaving liquid pockets with graphene at both sides, and (iii) a spacer material with liquid pockets covered at both sides by graphene. A total of four different process flows are available for liquid cell assembly, but there is not yet a consensus on the best routes, and a number of variations exist. The key step is the transfer of graphene to a liquid sample, which is complicated by practical issues that arise from imperfections in the graphene sheets, such as cracks. This review provides an overview of these different approaches to assembling graphene liquid cells and discusses the main obstacles and ideas to overcome them with the prospect of developing the nanoscale technology needed for graphene liquid cells so that they become available on a routine basis for electron microscopy in liquid. It also provides guidance in selecting the appropriate type of graphene liquid cell and the best assembly method for a specific experiment. PMID- 29799209 TI - Anisotropic Rolling and Controlled Chirality of Nanocrystalline Diamond Nanomembranes toward Biomimetic Helical Frameworks. AB - Future advances in materials will be aided by improved dimensional control in fabrication of 3D hierarchical structures. Self-rolling technology provides additional degrees of freedom in 3D design by enabling an arbitrary rolling direction with controllable curvature. Here, we demonstrate that deterministic helical structures with variable rolling directions can be formed through releasing a strained nanomembrane patterned in a "utility knife" shape. The asymmetry of the membrane shape provides anisotropic driving force generated by the disparity between the etching rates along different sides in this asymmetric shape. A transient finite element method (FEM) model of diagonal rolling is established to analyze the relationships among geometries, elastic properties, and boundary conditions. On the basis of this model, a diamond-based helical framework consisting of two or three helical segments has been fabricated to mimic the shapes of natural plants. Further experiment has been done to extend this approach to other materials and material combinations, such as MoSe2/Cr, Cr/Pt, and VO2. To demonstrate the possible application accessible by our technology to new fields, VO2-based helical microscale actuation has been demonstrated with photocontrollable bending in a selected region, as well as morphable and recognizable helix. This study offers a new way to construct helical mesostructures that combine special properties of the advanced materials, thus possess novel features and potential applications. PMID- 29799211 TI - Hospitalizations, active component, U.S. Armed Forces, 2017. PMID- 29799210 TI - Absolute and relative morbidity burdens attributable to various illnesses and injuries, active component, U.S. Armed Forces, 2017. PMID- 29799212 TI - Ambulatory visits, active component, U.S. Armed Forces, 2017. PMID- 29799213 TI - Surveillance snapshot: Illness and injury burdens, reserve component, U.S. Armed Forces, 2017. PMID- 29799214 TI - Surveillance snapshot: Illness and injury burdens, recruit trainees, active component, U.S. Armed Forces, 2017. PMID- 29799216 TI - Absolute and relative morbidity burdens attributable to various illnesses and injuries, non-service member beneficiaries of the Military Health System, 2017. PMID- 29799215 TI - Morbidity burdens attributable to various illnesses and injuries, deployed active and reserve component service members, U.S. Armed Forces, 2017. PMID- 29799217 TI - Uncovering the Connection Between Low-Frequency Dynamics and Phase Transformation Phenomena in Molecular Solids. AB - The low-frequency motions of molecules in the condensed phase have been shown to be vital to a large number of physical properties and processes. However, in the case of disordered systems, it is often difficult to elucidate the atomic-level details surrounding these phenomena. In this work, we have performed an extensive experimental and computational study on the molecular solid camphor, which exhibits a rich and complex structure-dynamics relationship, and undergoes an order-disorder transition near ambient conditions. The combination of x-ray diffraction, variable temperature and pressure terahertz time-domain spectroscopy, ab initio molecular dynamics, and periodic density functional theory calculations enables a complete picture of the phase transition to be obtained, inclusive of mechanistic, structural, and thermodynamic phenomena. Additionally, the low-frequency vibrations of a disordered solid are characterized for the first time with atomic-level precision, uncovering a clear link between such motions and the phase transformation. Overall, this combination of methods allows for significant details to be obtained for disordered solids and the associated transformations, providing a framework that can be directly applied for a wide range of similar systems. PMID- 29799218 TI - Exact Local Correlations and Full Counting Statistics for Arbitrary States of the One-Dimensional Interacting Bose Gas. AB - We derive exact analytic expressions for the n-body local correlations in the one dimensional Bose gas with contact repulsive interactions (Lieb-Liniger model) in the thermodynamic limit. Our results are valid for arbitrary states of the model, including ground and thermal states, stationary states after a quantum quench, and nonequilibrium steady states arising in transport settings. Calculations for these states are explicitly presented and physical consequences are critically discussed. We also show that the n-body local correlations are directly related to the full counting statistics for the particle-number fluctuations in a short interval, for which we provide an explicit analytic result. PMID- 29799219 TI - LISA Sources in Milky Way Globular Clusters. AB - We explore the formation of double-compact-object binaries in Milky Way (MW) globular clusters (GCs) that may be detectable by the Laser Interferometer Space Antenna (LISA). We use a set of 137 fully evolved GC models that, overall, effectively match the properties of the observed GCs in the MW. We estimate that, in total, the MW GCs contain ~21 sources that will be detectable by LISA. These detectable sources contain all combinations of black hole (BH), neutron star, and white dwarf components. We predict ~7 of these sources will be BH-BH binaries. Furthermore, we show that some of these BH-BH binaries can have signal-to-noise ratios large enough to be detectable at the distance of the Andromeda galaxy or even the Virgo cluster. PMID- 29799220 TI - Fracton-Elasticity Duality. AB - Motivated by recent studies of fractons, we demonstrate that elasticity theory of a two-dimensional quantum crystal is dual to a fracton tensor gauge theory, providing a concrete manifestation of the fracton phenomenon in an ordinary solid. The topological defects of elasticity theory map onto charges of the tensor gauge theory, with disclinations and dislocations corresponding to fractons and dipoles, respectively. The transverse and longitudinal phonons of crystals map onto the two gapless gauge modes of the gauge theory. The restricted dynamics of fractons matches with constraints on the mobility of lattice defects. The duality leads to numerous predictions for phases and phase transitions of the fracton system, such as the existence of gauge theory counterparts to the (commensurate) crystal, supersolid, hexatic, and isotropic fluid phases of elasticity theory. Extensions of this duality to generalized elasticity theories provide a route to the discovery of new fracton models. As a further consequence, the duality implies that fracton phases are relevant to the study of interacting topological crystalline insulators. PMID- 29799221 TI - Ionic Impurity in a Bose-Einstein Condensate at Submicrokelvin Temperatures. AB - Rydberg atoms immersed in a Bose-Einstein condensate interact with the quantum gas via electron-atom and ion-atom interaction. To suppress the typically dominant electron-neutral interaction, Rydberg states with a principal quantum number up to n=190 are excited from a dense and tightly trapped micron-sized condensate. This allows us to explore a regime where the Rydberg orbit exceeds the size of the atomic sample by far. In this case, a detailed line shape analysis of the Rydberg excitation spectrum provides clear evidence for ion-atom interaction at temperatures well below a microkelvin. Our results may open up ways to enter the quantum regime of ion-atom scattering for the exploration of charged quantum impurities and associated polaron physics. PMID- 29799222 TI - Experimental Observation of One-Dimensional Superradiance Lattices in Ultracold Atoms. AB - We measure the superradiant emission in a one-dimensional (1D) superradiance lattice (SL) in ultracold atoms. Resonantly excited to a superradiant state, the atoms are further coupled to other collectively excited states, which form a 1D SL. The directional emission of one of the superradiant excited states in the 1D SL is measured. The emission spectra depend on the band structure, which can be controlled by the frequency and intensity of the coupling laser fields. This work provides a platform for investigating the collective Lamb shift of resonantly excited superradiant states in Bose-Einstein condensates and paves the way for realizing higher dimensional superradiance lattices. PMID- 29799223 TI - Nonlinear Focal Modulation Microscopy. AB - We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ~60 nm (~lambda/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique. PMID- 29799225 TI - Out-of-Bounds Hydrodynamics in Anisotropic Dirac Fluids. AB - We study hydrodynamic transport in two-dimensional, interacting electronic systems with merging Dirac points at charge neutrality. The dispersion along one crystallographic direction is Dirac-like, while it is Newtonian-like in the orthogonal direction. As a result, the electrical conductivity is metallic in one and insulating in the other direction. The shear viscosity tensor contains six independent components, which can be probed by measuring an anisotropic thermal flow. One of the viscosity components vanishes at zero temperature leading to a generalization of the previously conjectured lower bound for the shear viscosity to entropy density ratio. PMID- 29799224 TI - Elastohydrodynamic Lift at a Soft Wall. AB - We study experimentally the motion of nondeformable microbeads in a linear shear flow close to a wall bearing a thin and soft polymer layer. Combining microfluidics and 3D optical tracking, we demonstrate that the steady-state bead to-surface distance increases with the flow strength. Moreover, such lift is shown to result from flow-induced deformations of the layer, in quantitative agreement with theoretical predictions from elastohydrodynamics. This study thus provides the first experimental evidence of "soft lubrication" at play at small scale, in a system relevant, for example, to the physics of blood microcirculation. PMID- 29799227 TI - Broadband Control of Topological Nodes in Electromagnetic Fields. AB - We study topological nodes (phase singularities) in electromagnetic wave interactions with structures. We show that, when the nodes exist, it is possible to bind certain nodes to a specific plane in the structure by a combination of mirror and time-reversal symmetry. Such binding does not rely on any resonances in the structure. As a result, the nodes persist on the plane over a wide wavelength range. As an implication of such broadband binding, we demonstrate that the topological nodes can be used for hiding of metallic objects over a broad wavelength range. PMID- 29799226 TI - First Extraction of Transversity from a Global Analysis of Electron-Proton and Proton-Proton Data. AB - We present the first extraction of the transversity distribution in the framework of collinear factorization based on the global analysis of pion-pair production in deep-inelastic scattering and in proton-proton collisions with a transversely polarized proton. The extraction relies on the knowledge of dihadron fragmentation functions, which are taken from the analysis of electron-positron annihilation data. For the first time, the transversity is extracted from a global analysis similar to what is usually done for the spin-averaged and helicity distributions. The knowledge of transversity is important for, among other things, detecting possible signals of new physics in high-precision low energy experiments. PMID- 29799228 TI - Integrable Time-Dependent Quantum Hamiltonians. AB - We formulate a set of conditions under which the nonstationary Schrodinger equation with a time-dependent Hamiltonian is exactly solvable analytically. The main requirement is the existence of a non-Abelian gauge field with zero curvature in the space of system parameters. Known solvable multistate Landau Zener models satisfy these conditions. Our method provides a strategy to incorporate time dependence into various quantum integrable models while maintaining their integrability. We also validate some prior conjectures, including the solution of the driven generalized Tavis-Cummings model. PMID- 29799229 TI - Observable Windows for the QCD Axion Through the Number of Relativistic Species. AB - We show that when the QCD axion is directly coupled to quarks with c_{i}/f?_{MU}aq[over -]_{i}gamma^{MU}gamma^{5}q_{i}, such as in Dine-Fischler Srednicki-Zhitnitsky models, the dominant production mechanism in the early Universe at temperatures 1 GeV?T?100 GeV is obtained via q_{i}q[over -]_{i}< >ga and q_{i}g<->q_{i}a, where g are gluons. The production of axions through such processes is maximal around T~m_{i}, where m_{i} are the different heavy quark masses. This leads to a relic axion background that decouples at such temperatures, leaving a contribution to the effective number of relativistic degrees of freedom, which can be larger than the case of decoupling happens the electroweak phase transition, DeltaN_{eff}?0.027. Our prediction for the t quark is 0.027<=DeltaN_{eff}<=0.036 for 10^{6} GeV?f/c_{t}?4*10^{8} GeV and for the b quark is 0.027<=DeltaN_{eff}<=0.047 for 10^{7} GeV?f/c_{b}?3*10^{8} GeV. For the c quark the window can only be roughly estimated as 0.027